IHP Magazine - October 2011

IHP OCTOBER 2011 | $14.95

Does cholesterol drive heart disease?

Meditation and attention-deficit/hyperactivity disorder

Cannabis and psychosis risk

By William R Ware, PhD

By Elizabeth J Cherevaty, ND

By Lorraine Stuyt, ND

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Continuing Education: Mammography for breast cancer screening- an update of the evidence

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High bioavailability potential Calcium and magnesium are delivered in citrate form providing superior bioavailability and protection from bone loss.3* 1. Natural Health Products Directorate (NHPD). Product Monograph – Multi-Vitamin/Mineral Supplement [internet] October 22, 2007 [Accessed Sept 17 2010]. Available at: http://www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/ licen-prod/monograph/multi_vitmin_suppl-eng.php.

2. NHPD. Product Monograph – Multi-Vitamin/Mineral Supplement. 2007.

3. J Clin Pharmacol. 2000;40:1237-12.

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PUBLISHERS LETTER

Let’s Talk

One of the most important lessons acquired in life is effective communication and team-building.

Communication that is clear but respectful is crucial in building healthy relationships, both in the personal and professional sphere. In the professional world, it ensures that all team members first share a common understanding of the endpoint, and then understand their own roles in executing the operative strategy. At IHP, our goal is to provide you - MDs, NDs, DCs - with a high-quality, scientific publication featuring developments in Integrative Medicine, in order to improve patient care and facilitate interprofessional communication.

To better help us achieve this end, we have recently expanded our team to include Angela MacNeil, MSc, ND, as our Editorial Assistant. Angela is a graduate of the University of Waterloo, University of Guelph, and the Canadian College of Naturopathic Medicine; she will be coordinating the peer review process, and continuing progress toward securing Pubmed/ Medicine-listing. We are very grateful to have her on board in this important role.

As always, we at IHP welcome your feedback and would love to hear how our team can better assist you in further improving your practice and your patient care.

SJagota­

www.facebook.com/IHPMag

www.twitter.com/IHPMag TM

Photograph by Scott Jordan

Sanjiv Jagota Publisher

4 | IHP October 2011 } ihpmagazine.com

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NEURAPAS® balance is a well-tolerated herbal remedy that produces favourable results in the treatment of mental illnesses, particularly those of a depressive nature, because of its well-balanced composition and various pharmacological effects.

* NEURAPAS® balance has positive effects on imbalanced mood, and inner restlessness, as well as the ability to regulate sleep habits.1 * The results of a randomized placebo-controlled trial represented the superior efficacy of NEURAPAS® balance over placebo in the treatment of depressive disorders, sleep disorders and anxiety associated with depression, as well as the maintenance or restoration of a stable mood.2 * NEURAPAS® balance is authorized in Austria as traditional herbal medicine for the treatment of: emotional depressive conditions (such as those accompanied by loss of interest, low mood, listlessness); insomnia due to nervousness.

1. Acta Biologica, Nr 1, July 2006.

2. Urlea-Schön, I., Wartenberg-Demand, A., McGregor, G. (2003)

N AT U R A L M E D I C I N E

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Product Information

NPN: 80025095 Each tablet contains: Dry extract (4.6-6.5:1) St. John’s Wort Dry extract (3.8-5.6:1) valerian root Dry extract (6.25-7.1:1) passionflower

60mg 28mg 32mg

Dosage: Adults and children (12 and up): 2 tablets 1-3 times daily. Children (6-11): 1 tablet 1-3 times daily.

Detailed Information:

Figure1: Effect of NEURAPAS® balance on HAMD scores versus placebo

Clearly stress is becoming more and more common.

People are feeling overwhelmed by the demand to balance pressures at work with responsibilities to home and society. Symptoms are wide-ranging and include sleep disturbances, anxiety, despondence, lack of drive, fatigue, lack of motivation, headache, lack of concentration.

Stress and burnout can have more serious implications: a recent study found that workplace stress is associated with a 50% increase in risk for coronary heart disease1.

compared with placebo, as measured by the Hamilton Depression Scale3. This fast-acting relief is likely due to its effects on easing anxiety and promoting healthier sleeping patterns.

NEURAPAS® balance has a combination of ingredients which work synergistically to relieve the symptoms of burnout and stress, including imbalanced mood and sleep disturbances. Each ingredient has years of research supporting its effectiveness. In addition, studies have shown that Passionflower has a specific synergistic effect on St. John’s wort, which lowers the dose of St. John’s wort required for the same biological effect by 9/10ths, a very significant synergy2.

A 2006 study found that NEURAPAS® balance has a significant impact on normalizing sleep patterns as measured by sleep EEGs, as well as reducing objectivelymeasured duration of wake-time at night even in healthy patients7.

Several clinical studies have shown conclusively that NEURAPAS® balance has a clinically significant antidepressant effect3,4. In addition, because of the unique synergy--meaning smaller amounts of St. John’s wort achieve the same therapeutic effect-NEURAPAS® balance has been shown to have no effect on liver enzymes at therapeutic doses5. Therefore the concern for side effects traditionally observed with St. John’s wort is not a problem with NEURAPAS® balance.

In the treatment of mild to moderate depression, NEURAPAS® balance has been shown to have a statistically-significant effect after only 2 weeks of treatment,

St. John’s wort has also been shown to have an effect on the hypothalamic-pituitary-adrenal (HPA) axis, regulating the production of cortisol without having to stimulate adrenal function to alleviate stress6.

Clearly, this well-balanced combination of St. John’s Wort, valerian and passionflower in NEURAPAS® balance has possitive effects on balancing mood and regulating sleep disorders caused by stress and agitation. For more information and full research, visit our website.

References:

1. Kivimaki et al. (2006) Work stress in the etiology of coronary heart disease--a metaanalysis. Scand. J. Work Environ. Health. 32:431-42.

2. Fiebich et al. (2011) Pharmacological studies in an herbal drug combination of St. John’s wort (Hypericum perforatum) and passion flower (Passiflora incarnata): In vitro and in vivo evidence of synergy between Hypericum and Passiflora in antidepressant pharmacological models. Fitotherapia 82: 474-480.

3. Urlea-Schön et al. (2003) Efficacy of a triple herbal preparation in mild depressive disorders: results of a randomised placebo-controlled trial. Focus Compl. Alt. Therp.

4. Krick (2005) unpublished.

5. Pascoe Naturmedizin (2004) Neurapas: Measurement of cytochrome P450 induction on enzyme activity level in cryopreserved, plated human hepatocytes.T-08-2004.

6. Butterweck et al. (2004) Flavonoids of St. John’s wort reduce HPA axis function in the rat. Planta Med. 70:1008-11.

7. McGregor et al. (2006) Triple combination in NEURAPAS balance demonstrates a unique effect on sleep EEGs. Acta Biologica. 1:3-14.

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A novel solution for the prophylaxis of urinary tract infections (utis)

ISSN 1920-4302 | OCTOBER 2011 Volume 4 • Issue 5

Publisher | Sanjiv Jagota - ext. 6122 Editor-in-Chief | Philip Rouchotas, MSc, ND - ext. 6109 Associate Editor | Angela MacNeil, MSc, ND • K.C. Bateman, ND Art Director | Scott Jordan Design | Sarah Vincett Production | James Shotton Contributors William R. Ware, PhD Lorraine Stuyt, ND Elizabeth J. Cherevaty, ND Angela MacNeil, MSc, ND Philip Rouchotas, MSc, ND Christopher Habib, ND

The perfect combination for keeping UTI producing E. coli bacteria away Highly concentrated Cranberry Extract (35:1) equivalent to 20 g fresh fruit/day combined with 1.6 g of natural D-Mannose at recommended daily dosage Ultra convenient vegetarian capsules allow for ease of use with even your most active patients

President | Olivier Felicio - ext. 6107 Controller & Operations | Melanie Seth - ext. 6114 Finance Administrator | Leslie Witol Web Designer | Matthew Pomepey Customer Service | Marsha Miller - ext. 6126 Advertising Information Sanjiv Jagota Telephone: (416) 203-7900 ext 6125 Email: sanjiv@ihpmagazine.com

Jeff Yamaguchi Telephone: (416) 203-7900 ext 6122 Email: jeff@gorgmgo.com

Paul Airut Telephone: (416) 203-7900 ext 6103 Email: paul@gorgmgo.com

Erin Poredos Telephone: (416) 203-7900 ext 6128 Email: erin@gorgmgo.com

Circulation Garth Atkinson | Publication Partners 345 Kingston Rd., Suite 101 Pickering, Ontario, L1V 1A1 Telephone: 1-877-547-2246 Fax: 905-509-0735 Email: ihp@publicationpartners.com

Cran-Mannose UTI™ A high potency combination for the treatment of acute recurrent urinary tract infections due to E. coli and the prophylaxis of recurrent infections.

Subscription Rates Canada $80 (gst included) for six issues | $120 International Published by

Canada Post Canadian Publication Mail Agreement Number 4067800 Th e publisher does not assume any responsibility for the contents of any advertisement and any and all representations or warranties made in such advertising are those of the advertiser and not of the publisher. Th e publisher is not liable to any advertiser for any misprints in advertising not the fault of the publisher and in such an event the limit of the publisher’s liability shall not exceed the amount of the publisher’s charge for such advertising. No portion of this publication may be reproduced, in all or part, without the express written permission of the publisher. ihp magazine is pleased to review unsolicited submissions for editorial consideration under the following conditions: all material submitted for editorial consideration (photographs, illustrations, written text in electronic or hard copy format) may be used by ihr Media Inc. and their affiliates for editorial purposes in any media (whether printed, electronic, internet, disc, etc.) without the consent of, or the payment of compensation to, the party providing such material. Please direct submissions to the Editor, ihp magazine.

Improving health and wellness…naturally

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Look for Dr. Pizzorno’s BioFoundation-G Product Insight at www.bioclinicnaturals.com

BioFoundation-G, formulated by Dr. Joseph Pizzorno, is a broad spectrum multivitamin and mineral formula based on clinical research providing an extensive nutritional foundation plus advanced glutathione support.

Formulas that work, products you can count on.

• Provides rate limiting nutrients for glutathione production, necessary for xenobiotic detoxification • Full spectrum multiple vitamin and mineral with 2000 IU vitamin D3 per serving • Contains clinical doses of resveratrol, R-alpha lipoic acid, CoQ10, milk thistle and green tea extract • Broad spectrum antioxidant support, including bilberry and citrus extracts, R-alpha lipoic acid, lycopene and lutein

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• Highly bioactive and bioavailable nutrients, such as pyridoxal-5-phosphate and vitamin K2 (Menaquinone 7)

01/09/11 9:48 AM 9/29/11 11:58:39 AM

clinical highlight

Detoxification

is toxin exposure clinically relevant?

hoW do toxins cause damage?

As many as 80,000 commercial and industrial chemicals are now in use in the United States, with hundreds more introduced into the marketplace on a weekly basis.1,2 Particularly troubling is the lack of information we have for the health effects that most of these substances have at chronic lowdose exposure. Furthermore, the effect of exposure on multiple substances simultaneously, which is the norm, is essentially unknown.3 For example, a recent study by the Agency for Toxic Substances and Disease Registry (ATSDR) found that when examining the components of 15 combinations and how they may interact, they predicted that 41% of them would have additive effects, 20% would have synergistic effects, but for 24% they did not have even the minimum information necessary to make a prediction. It has been estimated that at current funding levels, it would take 1,000 years to adequately document the health effects of the chemicals commonly encountered in commerce and industry.4 We know that considering the effect of one chemical at a time is no longer sufficient. The Centers for Disease Control (CDC) published data on the levels of selected persistent organic pollutants (POPs)—a category of toxins which includes dioxins, phthalates, PDBEs, PCBs, etc.—and found that among a representative sample of the US population, some toxins were present in essentially every individual over the age of 12, including, for example, p,p’-DDE and hexachlorobenzene.5 An analysis of NHANES data found up to a 38-fold adjusted increase in risk for diabetes prevalence in those with the highest levels of 6 POPs,6 and increased risk has also been documented for cardiovascular disease,7 insulin resistance, impaired neurological development, learning and attention deficit disorders, endometriosis, and deficits in the hypothalamic-pituitary-thyroid axis.8-11 While very little data for humans is available, current evidence suggests that PDBEs are likely to be developmental neurotoxins, and are likely to have synergistic effects with similar chemicals.12

Damage is caused through a variety of mechanisms, but most toxins do so by increasing oxidative stress, poisoning enzymes, directly damaging DNA or cellular membranes, or acting as endocrine disrupters. For example, the toxic metal cadmium increases oxidative damage by both causing the formation of free radicals such as H2O2 , O2 -, and OH, as well as by directly poisoning several enzymes which reduce oxidative stress, including catalase (CAT), glutathione reductase (GR), as well as the most abundant cellular antioxidant, glutathione (GSH).24-26 This is a fairly common mechanism for heavy metal toxicity.

In addition to exogenous toxins such as POPs and heavy metals, a number of endogenous substances also require efficient functioning of detoxification enzymes to prevent a build-up of harmful metabolites. For example, endotoxins from bowel flora have been associated with depression, chronic fatigue, inflammatory bowel disease, and atherosclerosis, effects partly influenced both by bacterial species as well as intestinal permeability.13-17 Also, catechol estrogens and estrogen quinones are estrogen derivatives associated with oxidative damage and reproductive tissue cancers, which accumulate due to alterations in enzymatic activity.18,19 Other examples are the build-up of methylmalonic acid and homocysteine—both metabolic by-products known to have vascular, renal, and neurological toxicity, consequences of genetic susceptibility and poor B vitamin status.20-23

An example of enzyme poisoning is the displacement of zinc with lead in the active site of the enzyme delta aminolevulinic acid dehydratase (ALAD), leading to a variety of behavioural and neurological abnormalities.27,28 The toxic metal, arsenic, has been shown to disrupt a number of hormonal pathways. It disrupts the thyroid hormone and retinoic acid receptors, and data from the 2003-2004 NHANES found elevated urinary levels of arsenic to be associated with the prevalence of Type 2 diabetes, likely by influencing genes associated with insulin sensitivity.29-31

Why is glutathione so important?

Glutathione is the most abundant intracellular antioxidant, and plays a crucial role in shielding cellular macromolecules from endogenous and exogenous reactive oxygen/nitrogen species. Of at least equal importance, conjugation with glutathione is also one of the leading detoxification pathways for many environmental toxins, which can cause direct cellular damage when glutathione regeneration is overwhelmed.32 Organochlorine pesticides and PCBs are both known to deplete glutathione levels and increase oxidative damage, an effect countered by supplementation with N-acetyl cysteine.33,34 Very recent research points to these and other persistent organic pollutants (POPs) as major drivers of diabetes and cardiovascular disease, with one large study documenting a 38-fold risk for those with the highest levels.

Additionally, serum GGT (which metabolizes reduced glutathione, allowing for intracellular synthesis) has emerged as a potential biomarker for exposure not only to POPs, but also to other toxins such as lead, cadmium and other exogenous causes of oxidative stress.35,36 Thus, supporting glutathione synthesis helps to conjugate harmful toxins, as well as protect cells from their damage, which seems to be underlying many chronic diseases. BioFoundation-G contains 150 mg N-acetyl cysteine and 250 mg alpha-lipoic acid per serving, both of which have been shown to increase glutathione levels, and to protect cells from numerous types of metal and organic toxins.37,38,39

FOR PROFESSIONAL USE ONLY. This product is not intended to diagnose, treat, cure or prevent any disease. © All Rights Reserved Bioclinic Naturals™ 2011. September 2011.

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Clinical Highlight

Bioactive vitamins at clinical doses BioFoundation-G contains clinically-relevant levels of vitamins not found in other multivitamins. For example, each serving provides 2000 IU of vitamin D3, 45 mcg vitamin K2 and 200 mg niacinamide. Given widespread vitamin D deficiency, a multivitamin with a higher dose helps to improve the multi-system consequences of sub-optimal levels.

Vitamin K has also emerged as an important factor not just to bone health, but to cardiovascular health as well. The form of vitamin K2 used in BioFoundation-G is menaquinone-7, known to have a longer half-life than other forms and result in more stable serum levels and critical to support deposition of calcium into bone rather than arteries.40

cellular energy/mitochondrial support Mitochondrial damage or inefficiency seems to underlie so many of today’s pathologies, typically due to poor diet and exogenous toxins, leading many clinicians to recommend supplemental nutrients such as CoQ10. BioFoundation-G contains 50 mg CoQ10 per serving, as well as 250 mg lipoic acid, both nutrients shown to enhance and protect mitochondrial function, providing many cardiovascular and metabolic benefits.41,42

antioxidant support & hepatoprotection BioFoundation-G provides diverse antioxidant support, as well as protection from hepatotoxins. For example, each serving contains 150 mg milk thistle, shown to provide protection from many environmental toxins, as well as 40 mg bilberry extract, 50 mg bioflavonoids, along with hesperidin, lycopene, and lutein.43 Rather than high levels of single antioxidants which causes imbalances, this formulation is designed to achieve superior results by ensuring adequate levels of synergistic nutrients.

Biological modifiers Finally, several plant-based nutrients have emerged as important regulators of cellular signalling pathways, and modify multiple biological processes thought to be involved in longevity-related functions. For example, resveratrol has remarkably similar effects to caloric restriction in terms of life span extension, and has been shown to improve insulin sensitivity, mitochondrial function and reduce inflammation.44,45,46 BioFoundation-G contains 50 mg resveratrol per serving, as well as 50 mg green tea extract.

references 1. Pohl H.R., Mumtaz M.M., Scinicariello F., Hansen H., “Binary weight-of-evidence evaluations of chemical interactions—15 years of experience,” Regul Toxicol Pharmacol, 2009; 54(3): 264-271.

2. De Rosa C.T., Hicks H.E., Ashizawa A.E., Pohl H.R., Mumtaz M.M., “A regional approach to assess the impact of living in a chemical world,” Ann N Y Acad Sci, 2006; 1076: 829-838.

3. Cory-Slechta D.A., “Studying toxicants as single chemicals: does this strategy adequately identify neurotoxic risk?,” Neurotoxicology, 2005; 26(4): 491-510.

4. De Rosa C.T., “Restoring the foundation: Tracking chemical exposures and human health,” Environ Health Perspect, 2003; 111(7): A374-375.

5. Patterson D.G. Jr., Wong L.Y., Turner W.E., et al., “Levels in the U.S. population of those persistent organic pollutants (2003-2004) included in the Stockholm Convention or in other long range transboundary air pollution agreements,” Environ Sci Technol, 2009; 43(4): 1211-1218.

6. Lee D.H., Lee I.K., Song K., et al., “A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999-2002,” Diabetes Care, 2006; 29(7): 1638-1644.

7. Ha M.H., Lee D.H., Jacobs D.R., “Association between serum concentrations of persistent organic pollutants and self-reported cardiovascular disease prevalence: results from the National Health and Nutrition Examination Survey, 1999-2002,” Environ Health Perspect, 2007; 115(8): 1204-1209.

8. Darras V.M., “Endocrine disrupting polyhalogenated organic pollutants interfere with thyroid hormone signaling in the developing brain,” Cerebellum, 2008; 7(1): 26-37.

9. Boersma E.R., Lanting C.I., “Environmental exposure to polychlorinated biphenyls (PCBs) and dioxins.

Consequences for long-term neurological and cognitive development of the child lactation,” Adv Exp Med Biol, 2000; 478: 271-287.

10. Lee D.H., Jacobs D.R., Porta M., “Association of serum concentrations of persistent organic pollutants with the prevalence of learning disability and attention deficit disorder,” J Epidemiol Community Health, 2007; 61(7): 591-596.

11. Lee D.H., Lee I.K., Jin S.H., Steffes M., Jacobs D.R. Jr., “Association between serum concentrations of persistent organic pollutants and insulin resistance among nondiabetic adults: results from the National Health and Nutrition Examination Survey 1999-2002,” Diabetes Care, 2007; 30(3): 622-628.

12. Costa L.G., Giordano G., “Developmental neurotoxicity of polybrominated diphenyl ether (PBDE) flame retardants,” Neurotoxicology, 2007; 28(6): 1047-1067.

13. Purohit V., Bode J.C., Bode C., et al., “Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium,” Alcohol, 2008; 42(5): 349-361.

14. Maes M., Kubera M., Leunis J.C., “The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression,” Neuro Endocrinol Lett, 2008; 29(1): 117-124.

15. Maes M., Coucke F., Leunis J.C., “Normalization of the increased translocation of endotoxin from gram negative enterobacteria (leaky gut) is accompanied by a remission of chronic fatigue syndrome,” Neuro Endocrinol Lett, 2007; 28(6): 739-744.

16. Caradonna L., Amati L., Magrone T., Pellegrino N.M., Jirillo E., Caccavo D., “Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance,” J Endotoxin Res, 2000; 6(3): 205-214.

17. Erridge C., Attina T., Spickett C.M., Webb D.J., “A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation,” Am J Clin Nutr, 2007; 86(5): 1286-1292.

18. Crooke P.S., Ritchie M.D., Hachey D.L., Dawling S., Roodi N., Parl F.F., “Estrogens, enzyme variants, and breast cancer: a risk model,” Cancer Epidemiol Biomarkers Prev, 2006; 15(9): 1620-1629.

19. Dawling S., Hachey D.L., Roodi N., et al., “In vitro model of mammary estrogen metabolism: structural and kinetic differences between catechol estrogens 2- and 4-hydroxyestradiol,” Chem Res Toxicol, 2004; 17(9): 1258-1264.

20. Perła-Kaján J., Twardowski T., Jakubowski H., “Mechanisms of homocysteine toxicity in humans,” Amino Acids, 2007; 32(4): 561-572.

21. Jakubowski H., “Pathophysiological consequences of homocysteine excess,” J Nutr, 2006; 136(6 Suppl): 1741S-1749S. 22. Kölker S., Okun J.G., “Methylmalonic acid—an endogenous toxin?,” Cell Mol Life Sci, 2005; 62(6): 621-624.

23. Morath M.A., Okun J.G., Müller I.B., et al., “Neurodegeneration and chronic renal failure in methylmalonic aciduria—a pathophysiological approach,” J Inherit Metab Dis, 2008; 31(1): 35-43.

24. Bertin G., Averbeck D., “Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review),” Biochimie, 2006; 88(11): 1549-1559.

25. Ercal N., Gurer-Orhan H., Aykin-Burns N., “Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage,” Curr Top Med Chem, 2001; 1(6): 529-539.

26. Kawata K., Yokoo H., Shimazaki R., Okabe S., “Classification of heavy-metal toxicity by human DNA microarray analysis,” Environ Sci Technol, 2007; 41(10): 3769-3774.

27. Warren M.J., Cooper J.B., Wood S.P., et al., “Lead poisoning, haem synthesis and 5-aminolaevulinic acid dehydratase,” Trends Biochem Sci, 1998 Jun; 23(6): 217-221.

28. affe E.K., Martins J., Li J., Kervinen J., Dunbrack R.L. Jr., “The molecular mechanism of lead inhibition of human porphobilinogen synthase,” J Biol Chem, 2001; 276(2): 1531-1537.

29. Díaz-Villaseñor A., Burns A.L., Hiriart M., Cebrián M.E., Ostrosky-Wegman P. “Arsenic-induced alteration in the expression of genes related to type 2 diabetes mellitus,” Toxicol Appl Pharmacol, 2007; 225(2): 123-133.

30. Navas-Acien A., Silbergeld E.K., Pastor-Barriuso R., Guallar E., “Arsenic exposure and prevalence of type 2 diabetes in US adults,” JAMA, 2008; 300(7): 814-822.

31. Davey J.C., Nomikos A.P., Wungjiranirun M., et al., “Arsenic as an endocrine disruptor: arsenic disrupts retinoic acid receptor-and thyroid hormone receptor-mediated gene regulation and thyroid hormone-mediated amphibian tail metamorphosis,” Environ Health Perspect, 2008; 116(2): 165-172.

32. Awasthi Y.C., et al, “Physiological and pharmacological significance of glutathione-conjugate transport,” J Toxicol Environ Health B Crit Rev, 2009 Aug; 12(7): 540-51.

33. Ahmed T., “Endosulfan-induced apoptosis and glutathione depletion in human peripheral blood mononuclear cells: Attenuation by N-acetylcysteine,” J Biochem Mol Toxicol, 2008 Sep; 22(5): 299-304.

34. Ludewig G., et al., “Mechanisms of toxicity of PCB metabolites: generation of reactive oxygen species and glutathione depletion,” Cent Eur J Public Health, 2000 Jul; 8 Suppl: 15-7.

35. Lee D.H., et al., “Serum gamma-glutamyltransferase: new insights about an old enzyme,” J Epidemiol Community Health, 2009 Nov; 63(11): 884-6.

36. Lee D.H., et al., “Is serum gamma glutamyltransferase a marker of oxidative stress?,” Free Radic Res, 2004 Jun; 38(6): 535-9.

37. Jain S., “Protective effect of N-acetylcysteine on bisphenol A-induced cognitive dysfunction and oxidative stress in rats,” Food Chem Toxicol, 2011 Mar 31.

38. Atkuri K.R., “N-Acetylcysteine – a safe antidote for cysteine/glutathione deficiency,” Curr Opin Pharmacol, 2007 Aug; 7(4): 355-9.

39. Shay K.P., et al., “Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential,” Biochim Biophys Acta, 2009 Oct; 1790(10): 1149-60.

40. Schurgers L.J., et al., “Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7,” Blood, 2007 Apr 15; 109(8): 3279-83.

41. “The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview,” Neurochem Res, 2008 Jan; 33(1): 194-203.

42. Rosenfeldt F., Marasco S., Lyon W., et al., “Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue,” J Thorac Cardiovasc Surg, 2005 Jan; 129(1): 25-32.

43. Kiruthiga P.V., Shafreen R.B., Pandian S.K., et al., “Silymarin protection against major reactive oxygen species released by environmental toxins: exogenous H2O2 exposure in erythrocytes,” Basic Clin Pharmacol Toxicol, 2007 Jun; 100(6): 414-9.

44. Baur J.A., et al., “Resveratrol improves health and survival of mice on a high-calorie diet,” Nature, 2006 Nov 16; 444(7117): 337-42.

45. Fröjdö S., et al., “Metabolic effects of resveratrol in mammals--a link between improved insulin action and aging,” Curr Aging Sci, 2008 Dec; 1(3): 145-51.

46. Brasnyó P., et al., “Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients,” Br J Nutr, 2011 Mar 9: 1-7. [Epub ahead of print]

FOR PROFESSIONAL USE ONLY. This product is not intended to diagnose, treat, cure or prevent any disease. © All Rights Reserved Bioclinic Naturals™ 2011. Sept 2011.

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EDITORS LETTER

Road Trip!

I had the privilege of attending the inaugural meeting of the Nova Scotia Association of Naturopathic Doctors in mid September. While a relatively small number of the nations NDs practice on the east coast, their impact on local communities was obvious. Questions posed by the audience during lectures and the presence of some immensely knowledgeable speakers, notably Ben Boucher, MD, Lise Alshuler, ND, and John Redden, demonstrated to me that east coast ND’s are a welcome force in Canada, and have been for many years. We wish Nova Scotia and neighbouring maritime provinces much success in their efforts to secure legislative standing.

We are excited to present Dr Esther Konigsberg, MD, as this issue’s cover story. Responsible for establishing the Introduction to Complementary and Alternative Medicine curriculum at McMaster University, Esther has made tremendous strides in increasing awareness of the art and practice of integrative medicine for generations of conventionally trained physicians to come.

This issue’s clinic profile features the Dundas Naturopathic Centre, home

to three of the most experienced NDs in the country. My visit to the facility was humbling, inspiring, and incredibly educational. The facility is a monument to the profession. I fear our story is incapable of articulating the world- class quality of care we had the privilege of witnessing.

This issue’s continuing education lesson provides an update on the controversial evidence surrounding mammogram screening recommendations. Dr Ware, PhD, provides a well- constructed and unique interpretation of evidence from major trials examining the role between plasma lipids and risk of coronary atherosclerosis.

Articles addressing meditation for management of ADHD and possible causal links between marijuana use and psychosis are also presented.

Best regards,

Philip Rouchotas, MSc, ND Editor-in-Chief

hotas

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We invite questions or comments. philip@ihpmagazine.com

ihpmagazine.com { October 2011 IHP | 11

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Product MonograPh Bio-Fen Bio-Fen Plus is an oral natural health product used in the treatment of hereditary androgenic alopecia (AGA) for male or female pattern baldness.

Without treatment, AGA is progressive, and causes social distress in many affected men and women (Sinclair 1998). Bio-Fen Plus contains extracts PROGRESSIVE NUTRITIONAL THERAPIES OMEGESSENTIAL™ of fenugreek seeds, saw palmetto berries and flax lignans, as well as specific vitamins. Each ingredient is known to possess inhibitors of the enzyme 5α-reductase.OmegEssential™ These inhibitors are for relieving symptoms associated with hereditary Progressive is responsible a high potency blend of cold water, wild caught, purified AGA. fish oil along with a family of strategic support nutrients.

One of the primary causes of hair loss is a high level of the male hormone dihydrotestosterone (DHT) within the hair follicle (Vierhapper, 2001).

For people with AGA, their follicles have a greater number of androgen receptors to which DHT attaches. 5-α-reductase catalyzes the enzymatic Fish Oils for the Maintenance of Good Health which binds to the receptor five-fold more avidly than the parent compound (Sinclair 1998). conversion of testosterone to dihydrotestosterone, As a source of omega-3 fatty acids, namely EPA and DHA, fish oils aid in the maintenance of good health, help support cognitive health/brain Vitamins Saw palmetto repens) health (NHPD Monograph: Fish Oil). function and (Serenoa cardiovascular In a Polish study of 46 women who had symptoms of diffuse alopecia, calcium Standardized (lipophillic) Serenoa extract has been found to be a potent inhibitor was orally twice a day inindoses of 100 mg for four to of 5α-reductase, resultingconducted in decreasedatissue An open-label, doseof response Fontani, et al (2005) studyDHT. to evaluate the effect omega-3pantothenate supplementation on administered cognitive performance 33 normal healthy men months,types and vitamin B6 was were injected everyalong day forwith 20 tothe 30 Profile days andofrepeated studywomen was conducted malesduring to determine the effect of aTests combination and (agedon 2242– healthy 51 years) a 35-day period. involvingfive different of attention used, Mood six months (Brzezińska-Wcisło 2001). It wasstates determined vitamin of carotenoid astaxanthin andshowed saw palmetto berryprofile lipid extract on DHT and States (POMS).

Results a mood with increased vigour again and after reduced anger, anxiety and depression afterthat omega-3.

B6 administered parenterally forofa attentional few weeks induces improvement functions, in the hair testosterone levels (Angwafor 2008). that The omega-3 men were supplementation divided into two groups: Furthermore, findings indicated is associated with an improvement and physiological condition in a subset of women and reduces hair loss. one group received mg/day the combination supplement and the other particularly those 800 involved in of complex cortical processing. group received 2000 mg/day of the supplement for 14 days. ANOVA-RM showed significant within-groupofincreases serum total testeosterone significant Higher consumption fish andin omega-3 fatty acids hasand been associated Medicinal with a lower risk of coronary heart diseasedose (CHD). et al (2002) Ingredients PerHu, capsule decreases in serum DHT from baseline in both dose groups (P=0.05). There examined the association between fish and omega-3 fatty acid consumption and risk of CHD in women. Dietary consumption and follow-up was no significant difference between dose groups with regard to the increase of Fenugreek (Trigonella graecum) diseasefoenum and cancer were compared data from 84,688 female nurses (aged 34 to 59 years) free from cardiovascular 260 mg from validated testeosterone or the decrease of DHT; therefore both doses were effective (Angwafor extract questionnaires. The outcomes indicated that women who consumed more seed fish and fish4:1 oil (omega-3 fatty acids) significantly reduced their risk 2008). of heart disease (particularly CHD deaths) by 30%, compared to women who rarely ate fish.

Saw palmetto berry extract containing 160 mg Another study tested liposterolic extract of Serenoa repens (LSESr) and beta45% free fatty acids Similarly, a prospective, nested case-control analysis was performed among apparently healthy men, who had no evidence of prior heart sitosterol in the treatment of males (23-64 years of age) with mild to moderate AGA. disease

by Albert, et al (2002) to improved addressatthe that long-chain omega-3 fatty standardized acids found intofish are associated with a reduced risk of Flax lignans, 20% Six of 10 (60%) subjects were rated as thehypothesis final visit, thus establishing 100 mgcollected blood of sudden death from cardiac causes. fatty-acid composition of whole blood in 184 men was compared(SDG) with the previously secoisolariciresinol diglucoside the effectiveness of 5α-reductase inhibitorsThe against AGA (Prager 2002). Chronic 94 men, in whom sudden death occurred as the first manifestation of cardiovascular disease.

The study reported that men who consumed inflammation of the hair follicle is considered to be a contributing factor for AGA. A D-calcium pantothenate (Vitamin B5) 10.40 mg long-chain omega-3 fattytoacids had whether a significantly risk of using sudden death. study by Chittur et al sought determine blockadereduced of inflammation LSESr and two anti-inflammatory agents (carnitine and thioctic acid) could alter Niacinamide (Vitamin B3) 10.25 mg Dosage the expression of molecular markers of inflammation (Chittur 2009). It was found Pyridoxine HCl (Vitamin B6) 2 mg that the combination suppressed lipopolysaccharide-activated gene expression of brain Indication: Fish Oil Supplement.

Helps support cardiovascular health, function and healthy mood balance. chemokines associated with pathways involved in inflammation and apoptosis.

Adults 19 years)that 5-alpha Dosage Riboflavin (Vitamin B2) 1.58 mg The study(≥concluded reductase inhibitors in combination with Takea2new softgels with breakfast 2 softgel with dinner for a total of 4 softgels per day. blockade of inflammatory processesSoftgels: could represent two-pronged approach and Folic acid 0.095 mg Liquid: Take 1 tsp (5ml) daily with food. in the treatment of AGA.

Biotin 400 mcg Interactions Fenugreek Seeds non-Medicinal Ingredients Fenugreek seeds to increase 30% protein, saponins, sterols, flavonoids Omega-3 fattycontain acids 5% may thesteroid risk of bleeding when taken with anticoagulants, aspirin, ginkgo biloba or ginseng (Mason, 2001). and alkaloids (notably trigonelline and choline). Steroid saponins bind and Therefore, medical supervision is required.

Inert microcrystalline cellulose and vegetable-based magnesium eliminate extra cholesterol and hormones in the body; DHT is made from stearate in a veggie-based capsule testosterone, which is in turn is made from cholesterol. Therefore, when excess Based on human studies, fish oils may lower blood pressure when taken in certain doses and have additive effects in patients treated with cholesterol is eliminated, less DHT can be made (Stark 1993). In a study of 20 anti-hypertensives (Prisco, et al, 1998). Use with caution.

Recommended adult dose: One capsule per day adults who consumed 12.5g and 18.0g of germinated fenugreek seed powder for one month, higher levels of consumption resulted in a significant reduction in total cholesterol and low-density lipoprotein (LDL) levels (Sowmya 1999).

Quality Assurance References

Flax lignans Parameter Albert C, et al (2002). Blood Levels of Long-Chain n-3 Fatty Acids Test Specifications Flax reduces the amount of DHT produced by reducing cholesterol levels in the and the Risk of Sudden Death. The New England Journal of Microbial body. A meta-analysis of 28 studies between 1990 and 2008 showed that flaxseed Medicine, Vol. 346 No. 15: 1113-1118, April 11.

Total Count USP Less than 1,000 cfu/g significantly reduces circulating total and LDL-cholesterol concentrations (Pan Yeast & Mold USP Less than 100 cfu/g Fontani G, et al (2005). Cognitive and physiological effects of 2009). Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L coli USP (95%Negative Omega-3 polyunsaturated fatty acid supplementation in healthy (95%Escherichia CI: -0.20, 0.00 mmol/L) and 0.08 mmol/L CI: -0.16, 0.00 mmol/L), Salmonella spp reductions were observed USP with Negative subjects. European Journal of Clinical Investigation, 35: 691-699. respectively.

Significant whole flaxseed (-0.21 and aureus USPand -0.16 Negative -0.16 Staphylococcus mmol/L, respectively) and lignan (-0.28 mmol/L, respectively) Hu F, et al (2002). Fish and Omega-3 Fatty Acid Intake and Risk Heavy Metal supplements (Pan 2009). of Coronary Heart Disease in Women. The Journal of the Arsenic USEPA Less than 0.25 ppm American Medical Association, Vol. 287 No. 14, April 10.

Cadmium USEPA Less than 0.25 ppm Lead USEPA Less than 0.25 ppm References Jellin JM, et al (2006). Pharmacist’s Letter/Prescriber’s Letter Angwafor F III, Anderson ML. An open label, dose response study to determine the effect on dihydrotestosterone, testosterone and estradiol levelsthin healthy males. J Total Mercury USEPA Less than 0.25 ppmof a dietary supplement Natural Medicines Comprehensive Database.8 ed. Stockton, Int Soc Sports Nutr 2008;5:12.

CA: Therapeutic Research Faculty.

Brzezińska-Wcisło L. Evaluation of vitamin B6 and calcium pantothenate effectiveness on hair growth from clinical and trichographic aspects for treatment of diffuse alopecia in women. Wiad Lek 2001;54:11-8.

Mason P. Dietary Supplements. 2nd ed. London: Pharmaceutical

Chittur S, Parr B, Marcovici G. Inhibition of inflammatory gene expression in keratinocytes using a composition containing carnitine, thioctic acid and saw palmetto extract. Evid Based Press; 2001.

Complement Alternat Med 2009.

NHPD Monograph. (2006). Fish Oil, August 8.

Pan A, Yu D, Demark-Wahnefried W, Franco OH, Lin X. Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr 2009;90:288-97.

Prisco the D,effectiveness et al (1998).

Effectderived of medium-term supplementation Prager N, Bickett K, French N, Marcovici G. A randomized, double-blind, placebo-controlled trial to determine of botanically inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia. J Altern Complement Med 2002;8:143-52. with a moderate dose of n-3 polyunsaturated fatty acids on blood Serenoa repens monograph. Alternative Medicine Review 1998;3:227-9.

pressure in mild hypertensive patients. Thromb Res. 1:105-12.

Sinclair R. Male pattern androgenetic alopecia. BMJ 1998;317:865-9.

Sowmya P, Rajyalakshmi P. Hypocholesterolemic effect of germinated fenugreek seeds in human subjects. Plant Foods Hum Nutr 1999;53:359-65.

Stark A, Madar Z. The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on bile acid absorption and cholesterol levels in rats, Br J Nutr 1993;69:277-87.

Vierpper H, Nowotny P, Maier H, Waldhausl W. Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/ dilution and mass spectrometry. J Clin Endocrinol Metab 2001;86:5762-4.

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48

contents OCTOBER 2011 VOLUME 4 – ISSUE 5

ARTICLES 48. Cover Story: Esther Konigsberg, MD

Bringing integrative medicine into medical school

56. Clinic Profile: Dundas Naturopathic Centre

What every ND aspires to be

62. Company Profile: St. Francis Herb Farm

A Family Business that’s 100% Canadian Owned and Canadian Operated

FEATURES 64. Does cholesterol drive coronary atherosclerosis?

A critical review of available evidence

71. Long-term Cannabis use

Increased risk of psychosis?

78. Meditation, Attention, and Neuroplasticity

Implications for the integrative care of attention-deficit/hyperactivity disorder

62 14 | IHP October 2011 } ihpmagazine.com

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78 COMING NEXT Issue

• Pregnancy morbidity and antiphospholipid syndrome • Omega-3 PUFA’s and fertility • Sodium- poison or biomarker?

56 departments 4. Publisher’s Letter 11. Editor’s Letter 18. Peer Review Board 22. Research News 38. Industry News 44. Product Profiles 86. Continuing Education: Mammography for Breast Cancer Screening

22

An update of the evident

94. Calendar/Events

ihpmagazine.com { October 2011 IHP | 15

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Curaphen

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Professional Pain Formula*†

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Featuring BCM-95® bioavailable curcumin • Results verified in human clinical trials • Enhanced absorption – up to 10 times better than alternative formulas • Extended therapeutic serum levels Proven Bioavailability. Curcumin’s bioavailability is poor. Therefore, clinical trials have used increasingly larger dosages (up to 10-12 grams daily). While no toxicity is associated with curcumin, even at these very high dosage levels, cost, comfort and compliance may be an issue.

New research has focused on approaches to improve curcumin’s bioavailability, such as adding lecithin and/or piperine. However, both of these absorption systems have inherent problems. In published animal (rat) studies, lecithin boosted absorption about five-fold, but there are no published human studies on bioavailability. Piperine does boost absorption, but it unfortunately interacts with a great many prescription medications, including anti-seizure, anti-hypertensive, inotropic, and cancer chemotherapeutic drugs.

Additionally, piperine may potentiate many environmental toxins, such as carbon tetrachloride1 and aflatoxin,2 and can cause hepatic stress.* 1. Piyachaturawat P, Kingkaeohoi S, Toskulkao C. Potentiation of carbon tetrachloride hepatotoxicity by piperine.

Drug Chem Toxicol. 1995;18(4):333-44.

2. Allameh A, Saxena M, Biswas G, Raj HG, Singh J, Srivastava N. Piperine, a plant alkaloid of the piper species, enhances the bioavailability of aflatoxin B1 in rat tissues. Cancer Lett. 1992;61(3):195-9

Absorption Comparison of Different Formulations of Curcumin

350 300 250 200 150 100 50 0

0

1

2

3

4

5

6

7

8

9

BCM-95® uses the safest and most successful method to enhance bioavailability by formulating curcumin with naturally-occurring phospholipids and turmeric essential oils. Human comparison testing has shown that this formula has up to 7-10 times (700 to 1000%) better bioavailability, as well as greater blood retention time, than standard curcumin 95% extracts, and 6.3 times (630%) more than curcumin complexed with lecithin and piperine. Additionally, 4 hours after ingestion, there is a 10 fold difference in serum peak levels between BCM-95 and plain curcumin.2

Time (hours)

Scientific Validation BCM-95® has been the subject of human bioavailability testing, as well as clinical trials on brain function, healthy HDL levels, and joint support.*1-4 Upcoming research will continue to investigate benefits for brain health and mental function, immune system support, and other areas of potential health benefits.*5-7 Published studies and trials in progress 1. Benny B, Antony B. Bioavailability of Biocurcumax (BCM-95). Spice India. 2006(September):11-15.

2. Antony B, Merina B, Iyer VS, Judy N, Lennertz K, Joyal S. A pilot cross-over study to evaluate human oral bioavailability of BCM-95, a novel bio-enhanced preparation of curcumin. Ind J Pharm Sci. 2008:445-450.

3. Baum L, Lam CWK, Cheung SKK, et al. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacology 2008; 28(1):110-114.

4. Curcumin effects on blood lipid profile in a 6-month human study (Elsevier Pharmacological Research. 2007;56:509-514.

5. Randomized, controlled human clinical study to assess the efficacy and safety of BCM-95 in the management of active rheumatoid arthritis.

Data in preparation for publication.

6. Phase II randomized, double-blind, placebo chemoprevention clinical trial of curcumin in oral premalignant lesions and cervical cancer. Study in progress.

7. Martins R. Evaluation of a novel preparation of curcumin (BCM-95) in patients with Alzheimer’s disease. Edith Cowan University, Australia. 2010.

Study in progress.

All ingredients established in human studies for safety and effectiveness.

Does not interfere with stomach, liver or kidney function.

BCM-95® and BosPure® are registered trademarks of Dolcas-Biotec. †Relief of occasional pain and inflammation associated with exercise or overuse.

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Terry Lemerond

Founder & President, EuroPharma,Inc./EuroMedica Terry Lemerond has 40 years of experience in the nutritional supplement industry. He has developed over 400 nutritional and botanical formulations that continue to be top selling products on the market today. Mr. Lemerond introduced the concept of botanical standardization to the United States, which revolutionized the natural products industry. He is also credited with introducing such firsts as glucosamine sulfate, St. Johns Wort, IP-6, standardized extracts and many others to the U.S. market.

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When Pain is the Problem, Curaphen® is the Answer.*† A unique combination, this fast-acting formula combines ingredients with multiple mechanisms of action to support the body’s natural anti-inflammatory response and relieve occasional muscle pain due to exercise and overuse.*

• Curcumin and boswellia support the reduction of inflammatory compounds in the body*

• DLPA sustains brain endorphin/enkephalin levels*

Featuring BCM-95® bioavailable curcumin Known for its ability to balance the body’s natural inflammatory response, BCM-95® has been proven in published clinical studies to provide consistent and long-lasting effects. The specialized process of micronizing and blending curcumin with turmeric essential oils and plant phospholipids increases both absorption and retention time in the bloodstream—up to 10 times stronger.*

BosPure® standardized boswellia (free of boswellic acids) Boswellia serrata is valued for its ability to block the activity of inflammatory cytokines. This activity is associated with the most active constituents in boswellia, boswellic acids. However, not every boswellic acid is beneficial. The presence of the less desirable boswellic acids can reduce the overall effectiveness of the extract. Therefore, BosPure® is specially produced to include only the beneficial compounds, including the most active boswellic acid – acetyl-11-keto-β-boswellic acid – and is free of the undesirable compounds (specifically, β-boswellic acid) that can potentially promote, rather than block, inflammatory cytokines.*

DLPA DLPA inhibits the breakdown of one of the brain’s natural pain-killing substances, enkephalins, which are in the same family as endorphins. The combination of the “L” and “D” forms of phenylalanine work synergistically to alleviate occasional pain due to exercise or overuse, and improve mood—two concerns that are physiologically interconnected.* Life Changing Results. Hundreds of patients have taken the time to contact us, relating their experience with Curaphen and how it has changed their lives for the better.

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A single ingredient formula containing BCM-95® bioavailable curcumin, CuraPro,™ is ideal for practitioners who wish to incorporate pure curcumin into their specific treatment protocols.

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BCM-95® and BosPure® are registered trademarks of Dolcas-Biotec.

†Relief of occasional pain and inflammation associated with exercise or overuse.

Key Code: ERPHS01 EM_BX103_0810

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PEER REVIEW

Peer Review Board Members Alfred Hauk, ND Holistic Healing Arts Centre 213 King George Road Brantford, Ontario N3R6S8 alf@ndoc.ca

Daniel Watters, ND Rosedale Wellness Centre 365 Bloor St East Toronto, Ontario M4W 3L4 wattersdaniel@hotmail.com

Allison Creech, MEd, ND Pure Health Natural Healthcare Solutions 10 Lawton Blvd Toronto, Ontario M2V1Z4 allisoncreech@gmail.com

Elizabeth Cherevaty, ND Meridian Wellness Centre 329 Woolwich St Guelph, Ontario N1H3W4 drliz@guelphnaturopathic.com

Aoife Earls, MSc, ND River Oaks Naturopathic and Wellness Centre 478 Dundas St West Oakville, Ontario L6H6Y3 aearlsnd@gmail.com

Erin Psota, ND 626 King St West, Suite 201 Toronto, Ontario M5V1M7 drpsota@gmail.com

Berchman Wong, ND Toronto, Ontario berchman.nd@gmail.com Carol Morley, ND Zawada Health 201 City Centre Drive Suite 404 Mississauga, Ontario L5B2G6 info@zawadahealth.com

George Tardik, ND Preventive Medical Health Centre 271 Spring Street Cobourg, Ontario K9A3K3 pmhc_nd@yahoo.com Heidi Fritz, MA, ND Research Fellow Canadian College of Naturopathic Medicine 1255 Sheppard Ave East Toronto, Ontario M2K1E2 hfritz@ccnm.edu

18 | IHP October 2011 } ihpmagazine.com

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PEER REVIEW

Jonathan E. Prousky, BPHE, MSc, ND Chief Naturopathic Medical Officer Professor, Clinical Nutrition Canadian College of Naturopathic Medicine 1255 Sheppard Ave East Toronto, Ontario M2K1E2 jprousky@ccnm.edu Jordan Robertson, ND Lakeshore Clinic 2159 Lakeshore Road Burlington, Ontario L7R1A5 jordanrobertsonnd@gmail.com Kevin Bernardo, ND Natural Food Pantry 2277 Riverside Drive Ottawa, Ontario K1H7X6 drkevinND@gmail.com Lee Know, ND Director of R&D Inno-Vite Inc 97 Saramia Cres Concord, Ontario L4K4P7 dr.know@inno-vite.com Leigh Arseneau, ND The Naturopathic Institute of Advanced Medicine 122 Simcoe St North Oshawa, Ontario L1G4S4 docleigh@gmail.com Lowell Greib, MSc, ND, CISSN Mahigan Medicine 19 Thomas Cres Hunstville, Ontario P1H2M3 info@mahiganmedicine.com Mandana Edalati Wellness Naturopathic Centre Suite 213-1940 Lonsdale Ave North Vancouver, British Columbia V7M2K2 dredalati@gmail.com Martin Downorowicz, ND Dicentra Inc 21 Phoebe Street Suite B002 Toronto, Ontario M5T1A8 martin.nd@naturopathicsource.com

Melanie DesChatelets, ND True Health Studio 200-4255 Arbutus St Vancouver, British Columbia V6J4R1 melanie@drdeschat.com Nicole Egenberger, ND Remede Naturopathics 214 Sullivan Street Suite 3B New York, New York 10012 info@remedenaturopathics.com Sarah Vadeboncoeur, ND Ottawa Integrative Health Centre 1129 Carling Ave Ottawa, Ontario K1Y4G6 sarahmvadeboncoeur@gmail.com Shawna Clark, ND Forces of Nature Naturopathic Clinic 2447 1/2 Yonge St Toronto, Ontario M4P2E7 info@shawnaclarknd.com Shehab El-Hashemy, MBChB, ND Associate Dean of Academic Delivery Canadian College of Naturopathic Medicine 1255 Sheppard Ave East Toronto, Ontario M2K1E2 selhashemy@ccnm.edu Tanya Lee, ND The Health Centre of Milton 400 Main St East Suite 210 Milton, Ontario L9T1P7 tanyalee.nd@gmail.com Terry Vanderheyden, ND Bayside Naturopathic Medicine 118 Bay Street Barry’s Bay, Ontario KOJ1B0 doctrv@gmail.com Tracey Teasdale, ND, CISSN Thompson Chiropractic 12 Fairview Road, Suite 105 Barrie, Ontario info@nd-sportsmed.com

ihpmagazine.com { October 2011 IHP | 19

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Furthermore, emerging evidence management suggests that the alkalinizing aregreens+ important contributors to way of achievingeffects compliance your recommendations to increase intake of fruit and has demonstrated the anti-cancer of fruitwith and vegetables. greens+ has specifically been researched forvegetables. this effect,Observational and was shownevidence to powerfully achieve in vivo protective associations for fruit and vegetable consumption and reduced cancer risk. Modern evidence has demonstrated that fruit and vegetables alkalinization. are powerful treatments for several cancers. Furthermore, emerging evidence suggests that the alkalinizing properties are important contributors to the anti-cancer effects of fruit and vegetables. greens+ has specifically been researched for this effect, and was shown to powerfully achieve in vivo alkalinization.

high vegetable intake demonstrated upregulation of genes controlling apoptosis, and down regulation of genes known to act as promotors of established colon tumours (van Breda 2004). high vegetable intake demonstrated upregulation of genes controlling apoptosis, and Very similar findings wereknown demonstrated men of with prostate cancer (Ornish down regulation of genes to act asamong promotors established colon tumours 2008).

Among a group of patients receiving intensive diet and lifestyle counselling (van Breda 2004). following diagnosis of prostate cancer, a sample of 30 of the men were assayed prior to enrollment following a wide array ofamong gene expression. and down-regulation Very similarand findings werefordemonstrated men with Up prostate cancer (Ornish of genes consistent with expectation of reduced andcounselling improved 2008).

Among a group of patients receiving intensivecarcinogenesis diet and lifestyle mechanisms of tumour apoptosis wereaidentified themen studywere population. following diagnosis of prostate cancer, sample of across 30 of the assayed prior to enrollment and following for a wide array of gene expression. Up and down-regulation Fruit and consistent vegetable intake and alkalinization of genes with expectation of reduced carcinogenesis and improved Research hasof shown thatapoptosis a seven-day of supplementation with a plant-based mechanisms tumour wereperiod identified across the study population. dietary product (greens+) increases urinary pH, potentially increasing the alkalinity of strips, the urinary pH of 18 men and 16 women the body 2008).

Using Fruit and(Berardi vegetable intake andpH alkalinization was measured for seven to establish urinary pH. with Upona enrollment, Research has shown that days a seven-day periodbaseline of supplementation plant-based participants were(greens+) asked to refrain from making significant changes the to their dietary dietary product increases urinary pH,any potentially increasing alkalinity of intake and/or exercise werepH asked avoid strips, thethey urinary of 18tomen andintroducing 16 women the body (Berardi 2008).habits.

Using In pHaddition, dietary supplements during 21-day study.

The plant-based supplement was was measured for seven days the to establish baseline urinary pH. Upon enrollment, ingested twice a day (8.5 per serving).

Whileany participants plant-based participants were asked to grefrain from making significantingested changesthe to their dietary nutritional supplement, urinaryInpH was re-measured wastofound statistically intake and/or exercise habits. addition, they wereand asked avoidtointroducing increase supplements (P=0.03) afterduring supplement ingestion. mean urinary pH was 6.07 was +/dietary the 21-day study.The The plant-based supplement 0.04 during thea baseline and increased 6.21 +/- 0.03 duringthetheplant-based first week ingested twice day (8.5 period g per serving).

Whiletoparticipants ingested of treatmentsupplement, and to 6.27 +/- 0.06 the secondand week treatment (Berardi nutritional urinary pH during was re-measured wasoffound to statistically 2008). figure 1.after supplement ingestion. The mean urinary pH was 6.07 +/increaseSee (P=0.03) 0.04 during the baseline period and increased to 6.21 +/- 0.03 during the first week 1: Changes in Urinary pHduring with Supplementation 2008). ofFigure treatment and to 6.27 +/- 0.06 the second week (Berardi, of treatment (Berardi 2008).

See figure 1.

6.40 6.35 Figure 1: Changes in Urinary pH with Supplementation (Berardi, 2008).

6.30 6.40 6.25 6.35 6.20 6.30 6.15 6.25 6.10 6.20 6.05 6.15 6.00 6.10 5.95 6.05 5.90 6.00 5.85 1 2 3 5.95 Week 5.90 5.85 1 2 3

Urinary pH Urinary pH

Observational studies show fruit and vegetable consumption predict reduced cancer risk The World Health Organization analyzed global fruit and vegetable consumption, and compared this tostudies global show rates offruit several chronic degenerative predict diseases,reduced notably Observational andmajor vegetable consumption heart disease cancer risk and cancer. Establishing 600g of fruit and vegetable consumption per day as aThe baseline estimates were made asglobal to thefruit global burden associated with Worldstandard, Health Organization analyzed anddisease vegetable consumption, and failing to achieve recommended intake.

Thechronic report degenerative concluded that if dailynotably intake compared this to this global rates of several major diseases, of fruit and vegetables to average 600g per and day,vegetable global burden of cardiovascular heart disease and cancer.were Establishing 600g of fruit consumption per day as would be reduced 31%, stroke esophageal cancer adisease baseline standard, estimates were made19%, as to stomach the globalcancer disease19%, burden associated with 20%, lung cancer 12% (Lock 2005).

TheThe totality of concluded observational shows failingand to achieve this recommended intake. report thatevidence if daily intake strong between and 600g vegetable consumption andofrisk of chronic of fruit correlations and vegetables were tofruit average per day, global burden cardiovascular degenerative notably heart disease andstomach cancer. cancer 19%, esophageal cancer disease woulddisease, be reduced 31%, stroke 19%, 20%, and lung cancer 12% (Lock 2005). The totality of observational evidence shows Intervention trials between of fruit fruit and and vegetable consumption among patients with strong correlations vegetable consumption and risk of chronic cancer degenerative disease, notably heart disease and cancer.

A mean of two years following successful conventional treatment for early-stage breast cancer, 1490 women assessed for a variety of diet and lifestyle notably Intervention trials ofwere fruit and vegetable consumption amongfactors, patients with BMI, physical activity, and fruit and vegetable consumption. Patients were followed cancer and vegetable formean sevenof years afterfollowing baseline successful assessment.

The pattern of high for fruit A two years conventional treatment early-stage breast intake than five plusofhigh activity (equivalent cancer, (greater 1490 women wereservings assessed per for aday) variety diet physical and lifestyle factors, notably to a 30 minuteactivity, walk six demonstrated profound protective effects BMI, physical anddays fruitper andweek) vegetable consumption.

Patients were followed relative to years other after studybaseline participants.

This combined lifestyle pattern predicted a 44% and vegetable for seven assessment.

The pattern of high fruit reduced(greater risk of all cause 30%per of study fell into activity this lifestyle pattern intake than fivedeath. servings day) participants plus high physical (equivalent (Pierce putsix thisdays in perspective, statins administered to protective individualseffects who to a 30 2007). minuteTowalk per week) demonstrated profound have survived heart participants. attack predict a reduced risklifestyle of all pattern cause death of 20-24% relative to othera study This combined predicted a 44% (McPherson 2006). reduced risk of all cause death. 30% of study participants fell into this lifestyle pattern (Pierce 2007). To put this in perspective, statins administered to individuals who Fruit survived and vegetable consumption changes geneticrisk expression in a manner have a heart attack predict a reduced of all cause death ofconsistent 20-24% with cancer prevention and/or treatment. More impressively, genes impacting cancer (McPherson 2006). prevention are benefited among individuals free of cancer, while genes involved in cancerand treatment are consumption benefited among patients withexpression cancer. in a manner consistent Fruit vegetable changes genetic with cancer prevention and/or treatment. More impressively, genes impacting cancer Twenty women with colorectal andfree eight control while women wereinvolved randomly amongadenomas individuals of cancer, genes in prevention are benefited assignedtreatment to a low are vegetable group (0.75 servings percancer. day) or a high vegetable group cancer benefited among patients with (three servings per day). All participants underwent baseline colonoscopy with biopsy, a second with biopsy performed followingwere the randomly two-week Twentyand women withcolonoscopy colorectal adenomas andwas eight control women intervention (van Breda 2004). tissue for expression assigned to aperiod low vegetable group (0.75Screening servings biopsied per day) colon or a high vegetable group of genes knownperto day). impact carcinogenesis/progression astonishing (three servings Allcolon participants underwent baselineyielded colonoscopy with findings. biopsy, and a second colonoscopy with biopsy was performed following the two-week intervention period (van Breda 2004). Screening biopsied colon tissue for expression Patients of cancer at baseline to “high” vegetable intake of genesfree known to impact colonassigned carcinogenesis/progression yieldeddemonstrated astonishing upregulation of genes responsible for deactivating carcinogens, and downregulation findings. of genes responsible for activation of carcinogens, relative to patients free of cancer at baseline to lowatvegetable intake. Patients with colon adenomas assigned to Patients assigned free of cancer baseline assigned to “high” vegetable intake demonstrated upregulation of genes responsible for deactivating carcinogens, and downregulation of genes responsible for activation of carcinogens, relative to patients free of cancer at baseline assigned to low vegetable intake. Patients with colon adenomas assigned to

Week

References Berardi JM, Logan AC, Rao AV. Plant based dietary supplement increases urinary pH. J Int Soc Sports Nutr 2008;5:20.

Lock K, Pomerleau J, Causer L, Altmann DR, McKee M. The global burden of disease attributable to low consumption of fruit and vegetables: implications for the global strategy on diet. Bull World Health Organ 2005;83:100-8.

References Berardi JM, Logan AC, Rao AV. Plant basedJ,dietary supplement increases urinary pH. J IntCardiovascular Soc Sports Nutr 2008;5:20.

McPherson R, Frohlich J, Fodor G, Genest Canadian Cardiovascular Society.

Canadian Society position statement--recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease. Can J Cardiol 2006;22:913-27.

Lock K, Pomerleau J, Causer L, Altmann DR, McKee M. The global burden of disease attributable to low consumption of fruit and vegetables: implications for the global strategy on diet. Bull World Health Organ 2005;83:100-8.

Ornish D, Magbanua MJ, Weidner G, Weinberg V, Kemp C, Green C, Mattie MD, Marlin R, Simko J, Shinohara K, Haqq CM, Carroll PR. Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention. Proc Natl Acad Sci USA 2008;105:8369-74.

McPherson R, Frohlich J, Fodor G, Genest J, Canadian Cardiovascular Society. Canadian Cardiovascular Society position statement--recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease.B,Can J CardiolL,2006;22:913-27.

Pierce JP, Stefanick ML, Flatt SW, Natarajan L, Sternfeld Madlensky Al-Delaimy WK, Thomson CA, Kealey S, Hajek R, Parker BA, Newman VA, Caan B, Rock CL. Greater survival after breast cancer in physically active women with high vegetable-fruit intake regardless of obesity. J Clin Oncol 2007;25:2345-51.

Ornish D, Magbanua MJ, Weidner G, Weinberg V, Kemp C, Green C, Mattie MD, Marlin R, Simko J, Shinohara K, Haqq CM, Carroll PR. Changes in prostate gene expression in men undergoing anvan intensive andMoonen lifestyleEJ, intervention.

Sci USAvegetable 2008;105:8369-74. van Breda SG, Agen E,nutrition Engels LG, Kleinjans JC,Proc vanNatl DelftAcad JH. Altered intake affects pivotal carcinogenesis pathways in colon mucosa from adenoma patients and controls. Carcinogenesis 2004;25:2207-16.

Pierce JP, Stefanick ML, Flatt SW, Natarajan L, Sternfeld B, Madlensky L, Al-Delaimy WK, Thomson CA, Kealey S, Hajek R, Parker BA, Newman VA, Caan B, Rock CL. Greater survival after breast cancer in physically active women with high vegetable-fruit intake regardless of obesity. J Clin Oncol 2007;25:2345-51. van Breda SG, van Agen E, Engels LG, Moonen EJ, Kleinjans JC, van Delft JH. Altered vegetable intake affects pivotal carcinogenesis pathways in colon mucosa from adenoma patients and controls. Carcinogenesis 2004;25:2207-16.

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RESEARCH NEWS

Dose-response relation found between physical activity and cognitive function A cross-sectional analysis examined the dose−response association between physical activity and cognitive function in Chinese subjects. A total of 27,651 participants aged 50 to 85 years were recruited from 2003 to 2008 and cognitive function was assessed by the delayed 10-word recall test (DWRT). Information on potential confounders, including demographic and anthropometric characteristics, socioeconomic position, lifestyle, and disease history, was collected by standardized interview and procedures.

Most participants were classified as physically active (53.1%), with 42.4% moderately active and 4.5% physically inactive. Significant dose−response relations were found across quintiles of metabolic equivalent value (METs) with DWRT score in participants with or without good self-rated health (all p for trend < 0.001). In participants with poor self-rated heath, those in the fifth quintile of METs compared to the first quintile had a significantly reduced risk of mild cognitive impairment by 28% (p < .01; p for trend = .006). The association between physical activity and DWRT score remained significant after adjustment for depression. The authors concluded that a significant dose−response relationship between physical activity and cognitive function was found and that the association was more pronounced in participants with poor self-rated health. Ann Epidemiol. 2011 Jul 22. PMID: 21784658

Secondhand smoke exposure increases the risk of neurobehavioral disorders among children The association between parent-reported postnatal secondhand tobacco smoke exposure in the home and neurobehavioral disorders (attention-deficit/hyperactivity disorder, learning disabilities, and conduct disorders) among children younger than 12 years in the United States was examined using the 2007 National Survey on Children’s Health. A total of 6% of 55 358 children (aged < 12 years) were exposed to secondhand smoke (SHS) in the home.

The weighted prevalence and 95% confidence intervals of each of the children’s neurobehavioral outcomes were 8.2% (7.5–8.8) with learning disabilities, 5.9% (5.5–6.4) with attention-deficit/ hyperactivity disorder, and 3.6% (3.1–4.0) with behavioral and conduct disorders. Children exposed to SHS at home had a 50% increased odds of having ≥2 childhood neurobehavioral disorders compared to children who were not exposed to SHS. Boys, older children (especially those aged 9 to 11 years), and children living in households with the highest poverty levels were at greater risk.

The authors concluded that the findings of the study, which are associational and not necessarily causal, underscore the health burden of childhood neurobehavioral disorders that may be attributable to SHS exposure in homes in the United States.

Pediatrics. 2011 Aug;128(2):263-270. PMID: 21746720

Decreased glutathione levels and impaired antioxidant enzyme activities found in early schizophrenia The current study was conducted to determine glutathione levels and antioxidant enzyme activities in the drug-naive first-episode patients with schizophrenia in comparison with healthy control subjects. Twenty-three patients in their first-episode of schizophrenia and 40 healthy control subjects were recruited in this case-controlled study. In patients, blood samples were obtained prior to the initiation of neuroleptic treatments. Glutathione levels, including total glutathione (GSHt), reduced glutathione (GSHr) and oxidized glutathione (GSSG), along with the antioxidant enzyme activities superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT), were determined by spectrophotometry.

Results revealed that GSHt, GSHr, and GPx activity were significantly lower in patients than in controls, whereas GSSG was significantly higher in patients. In addition, CAT activity was significantly lower in patients while the SOD activity was comparable to that of controls. The authors concluded that a glutathione deficit may be implicated in psychosis and may serve as an important indirect biomarker of oxidative stress in the early course of schizophrenia. These results provide support for further studies of the possible role of antioxidants as neuroprotective therapeutic strategies during the early stages of schizophrenia. BMC Psychiatry. 2011 Aug 2;11(1):124. PMID: 21810251

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RESEARCH NEWS

School age allergic disease is associated with reduced diversity of the intestinal microbiota during infancy Changes in human microbiota have been suggested as a risk factor for atopic diseases. In the current study, the association between neonatal fecal flora and the development of atopic disorders was investigated. The intestinal microbiota were examined in infants in a birth cohort of 411 high-risk children followed for six years by clinical assessments at 6-month intervals, as well as at acute symptom exacerbations. Bacterial flora was analyzed at 1 and 12 months of age and outcome measures included the development of allergic sensitization (skin test and specific serum IgE), allergic rhinitis, peripheral blood eosinophil counts, asthma, and atopic dermatitis. Results revealed that bacterial diversity in the early intestinal flora 1 and 12 months after birth was inversely associated with the risk of allergic sensitization (serum specific IgE P = .003; skin prick test P = .017), peripheral blood eosinophils (P = .034), and allergic rhinitis (P = .007). The authors concluded that reduced bacterial diversity of the infantâ&#x20AC;&#x2122;s intestinal flora was associated with increased risk of allergic sensitization, allergic rhinitis, and peripheral blood eosinophilia, but not asthma or atopic dermatitis, in the first six years of life. J Allergy Clin Immunol. 2011 Jul 20. PMID: 21782228

Chiropractic successfully manages postsurgical lumbar spine pain This retrospective chart review was conducted to assess the results of chiropractic management (including Cox flexion distraction technique) of patients with postsurgical lumbar spine pain to determine the change in reported pain based on surgical type.

Ten years of patient files from one chiropractic practice were screened for lumbar spine surgery occurring before presenting for chiropractic care. Of the 58 patients with a postsurgical diagnosis, 32 files contained all pertinent components for this study, including treatment with Cox flexion distraction manipulation (and adjunct procedures) for at least two weeks and pre- and post-treatment pain measures using the Numeric Pain Scale (NPS) that ranged from 0 (no pain) to 10 (worst pain imaginable). The mean change in pre- and post-treatment NPS pain scores decreased by 4.1 points and this was most remarkable in patients who underwent a surgery that combined lumbar discectomy, fusion, and/or laminectomy (the average NPS pain reduction score was 5.7). No adverse events were reported for any of these postsurgical patients. The authors concluded that patients treated with chiropractic care saw improvement in low back pain subsequent to lumbar spine surgery. J Manipulative Physiol Ther.

2011 July - August;34(6):408-412. PMID: 21807265

A homeopathic capsaicin nasal spray improves symptoms in subjects with a significant component of nonallergic rhinitis The efficacy of ICX72 (Sinus Buster), a proprietary homeopathic preparation of Capsicum annum and Eucalyptol, on nonallergic rhinitis (NAR) was investigated in this placebocontrolled study. Forty-two subjects were randomized to ICX72 (n = 20) or control (n = 22) administered twice daily for two weeks. Endpoints included: change in total nasal symptom scores (TNSS) from baseline to end of study; changes in individual symptom scores (ISS) over two weeks; average time to first relief; rhinitis quality-of-life; rescue medication; and safety endpoints. Mean TNSS and ISS were recorded after single dosing at different intervals over 60 minutes. Results revealed that ICX72 subjects exhibited significant differences in changes from baseline to end of study for TNSS and each ISS (P < .01) compared to controls. Average time to first relief was 52.6 seconds (P < .01) for ICX72 patients and improvement in nasal congestion, sinus pain, sinus pressure, and headache were noted at 5, 10, 15, and 30 minutes, persisting at 60 minutes (P < .05). Adverse events and rescue medication were similar between groups. This was the first controlled trial demonstrating that intranasal capsaicin rapidly and safely improves symptoms in rhinitis subjects. Ann Allergy Asthma Immunol. 2011 Aug;107(2):171-8. PMID: 21802026

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RESEARCH NEWS

Low serum 25-hydroxyvitamin D reduces postmenopausal breast cancer survival

Green tea intake lowers fasting serum total and LDL cholesterol in adults

The current study was conducted to assess the effect of post-diagnostic serum 25-hydroxyvitamin D [25(OH)D] concentrations on overall survival and distant disease-free survival in breast cancer patients. A prospective cohort study in Germany included 1295 incident postmenopausal breast cancer patients aged 50-74 years who were diagnosed between 2002 and 2005 and were followed up for a median of 5.8 years. Lower concentrations of 25(OH)D were linearly associated with higher risk of death (hazard ratio (HR) = 1.08 per 10 nmol/L decrement; 95% confidence interval (CI), 1.00 to 1.17) and significantly higher risk of distant recurrence (HR = 1.14 per 10 nmol/L decrement; 95%CI, 1.05 to 1.24). Compared with the highest tertile (55 nmol/L), patients within the lowest tertile (35 nmol/L) of 25(OH)D had a HR for overall survival of 1.55 (95%CI, 1.00 to 2.39) and a HR for distant disease-free survival of 2.09 (95%CI, 1.29 to 3.41). The association with overall survival was significant for 25(OH)D levels of blood samples collected before, but not after, the start of chemotherapy. The authors concluded that lower serum 25(OH)D concentrations may be associated with poorer survival in postmenopausal breast cancer patients. Breast Cancer Res. 2011 Jul 26;13(4):R74. PMID: 21791049

The effect of green tea beverage and green tea extract on lipid changes is controversial so the current study aimed to identify and quantify the effect of green tea and its extract on total cholesterol (TC), LDL cholesterol, and HDL cholesterol. A comprehensive literature search was performed to identify relevant trials of green tea beverages and extracts on lipid profiles in adults. Fourteen eligible randomized controlled trials with 1136 subjects were enrolled in the meta-analysis. Green tea consumption significantly lowered the TC concentration by 7.20 mg/dL (95% CI: −8.19, −6.21 mg/dL; P < 0.001) and significantly lowered the LDL-cholesterol concentration by 2.19 mg/dL (95% CI: −3.16, −1.21 mg/dL; P < 0.001). The mean change in blood HDL-cholesterol concentration was not significant. Subgroup and sensitivity analyses showed that these changes were not influenced by the type of intervention, treatment dose of green tea catechins, study duration, individual health status, or quality of the study. The authors concluded that the administration of green tea beverages or extracts resulted in significant reductions in serum TC and LDL-cholesterol concentrations, but no effect on HDL cholesterol was observed. Am J Clin Nutr. 2011; 94(2): 601-610. PMID: 21715508

Probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 improve bloating in patients with functional bowel disorders Recent data suggest a role for the intestinal microbiota in the pathogenesis of functional bowel disorders (FBDs). Unfortunately, probiotic studies in FBDs have generated inconsistent results suggesting a strain-specific and product-specific effect. A double-blind, placebocontrol clinical trial of a probiotic formula containing Lactobacillus acidophilus NCFM (L-NCFM) and Bifidobacterium lactis Bi-07 (B-LBi07) twice a day (2×10CFU/day) versus placebo over eight weeks was conducted to investigate its clinical efficacy in nonconstipation FBDs. Primary endpoints were global relief of gastrointestinal symptoms and satisfaction with treatment and secondary endpoints were change in symptoms severity, well-being, and quality of life. Sixty patients (31 subjects in the probiotic group and 29 subjects in the placebo group) were enrolled and abdominal bloating improved in the probiotic group compared with the placebo group at four weeks (4.10 vs 6.17, P=0.009; change in bloating severity P=0.02) and eight weeks (4.26 vs 5.84, P=0.06; change in bloating severity P<0.01).

The authors concluded that twice a day supplementation with L-NCFM and B-LBi07 improves symptoms of bloating in patients with FBDs and that these data support the role for probiotic bacteria in the management of these disorders. J Clin Gastroenterol. 2011 Jul;45(6):518-25. PMID: 21436726 24 | IHP October 2011 } ihpmagazine.com

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STOP HAIR LOSS!

BIO-FEN for everybody!

BIO-FEN PLUS aids in the treatment of hereditary androgenic alopecia (pattern baldness.) This patent-pending formula contains specific ratios of fenugreek, saw

For Men & Women

palmetto and flax lignans extracts. These ingredients are known to possess inhibitors

For details, write #106 on Free Info Page, page 96.

of the enzyme responsible for causing male or female pattern baldness. It also contains a mixture of B vitamins, folate and biotin to help suppport new hair growth.

Scientifically proven natural solution for hair loss Hair Grow Technology Inc. 1-866-424-7745 â&#x20AC;˘ www.biofen.com

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Product MonograPh Bio-Fen Bio-Fen Plus is an oral natural health product used in the treatment of hereditary androgenic alopecia (AGA) for male or female pattern baldness.

Without treatment, AGA is progressive, and causes social distress in many affected men and women (Sinclair 1998). Bio-Fen Plus contains extracts of fenugreek seeds, saw palmetto berries and flax lignans, as well as specific vitamins. Each ingredient is known to possess inhibitors of the enzyme 5α-reductase. These inhibitors are responsible for relieving symptoms associated with hereditary AGA. One of the primary causes of hair loss is a high level of the male hormone dihydrotestosterone (DHT) within the hair follicle (Vierhapper, 2001).

For people with AGA, their follicles have a greater number of androgen receptors to which DHT attaches. 5-α-reductase catalyzes the enzymatic conversion of testosterone to dihydrotestosterone, which binds to the receptor five-fold more avidly than the parent compound (Sinclair 1998).

Saw palmetto (Serenoa repens) Standardized (lipophillic) Serenoa extract has been found to be a potent inhibitor of 5α-reductase, resulting in decreased tissue DHT. An open-label, dose response study was conducted on 42 healthy males to determine the effect of a combination of carotenoid astaxanthin and saw palmetto berry lipid extract on DHT and testosterone levels (Angwafor 2008). The men were divided into two groups: one group received 800 mg/day of the combination supplement and the other group received 2000 mg/day of the supplement for 14 days. ANOVA-RM showed significant within-group increases in serum total testeosterone and significant decreases in serum DHT from baseline in both dose groups (P=0.05). There was no significant difference between dose groups with regard to the increase of testeosterone or the decrease of DHT; therefore both doses were effective (Angwafor 2008).

Another study tested liposterolic extract of Serenoa repens (LSESr) and betasitosterol in the treatment of males (23-64 years of age) with mild to moderate AGA. Six of 10 (60%) subjects were rated as improved at the final visit, thus establishing the effectiveness of 5α-reductase inhibitors against AGA (Prager 2002). Chronic inflammation of the hair follicle is considered to be a contributing factor for AGA. A study by Chittur et al sought to determine whether blockade of inflammation using LSESr and two anti-inflammatory agents (carnitine and thioctic acid) could alter the expression of molecular markers of inflammation (Chittur 2009). It was found that the combination suppressed lipopolysaccharide-activated gene expression of chemokines associated with pathways involved in inflammation and apoptosis.

The study concluded that 5-alpha reductase inhibitors in combination with blockade of inflammatory processes could represent a new two-pronged approach in the treatment of AGA. Fenugreek Seeds Fenugreek seeds contain 5% to 30% protein, steroid saponins, sterols, flavonoids and alkaloids (notably trigonelline and choline). Steroid saponins bind and eliminate extra cholesterol and hormones in the body; DHT is made from testosterone, which is in turn is made from cholesterol. Therefore, when excess cholesterol is eliminated, less DHT can be made (Stark 1993). In a study of 20 adults who consumed 12.5g and 18.0g of germinated fenugreek seed powder for one month, higher levels of consumption resulted in a significant reduction in total cholesterol and low-density lipoprotein (LDL) levels (Sowmya 1999).

Vitamins In a Polish study of 46 women who had symptoms of diffuse alopecia, calcium pantothenate was orally administered twice a day in doses of 100 mg for four to five months, and vitamin B6 was injected every day for 20 to 30 days and repeated again after six months (Brzezińska-Wcisło 2001). It was determined that vitamin B6 administered parenterally for a few weeks induces improvement in the hair condition in a subset of women and reduces hair loss.

Medicinal Ingredients

dose Per capsule

Fenugreek (Trigonella foenum graecum) seed extract 4:1

260 mg

Saw palmetto berry extract containing 45% free fatty acids

160 mg

Flax lignans, standardized to 20% secoisolariciresinol diglucoside (SDG)

100 mg

D-calcium pantothenate (Vitamin B5)

10.40 mg

Niacinamide (Vitamin B3)

10.25 mg

Pyridoxine HCl (Vitamin B6)

2 mg

Riboflavin (Vitamin B2)

1.58 mg

Folic acid

0.095 mg

Biotin

400 mcg

non-Medicinal Ingredients Inert microcrystalline cellulose and vegetable-based magnesium stearate in a veggie-based capsule Recommended adult dose: One capsule per day

Flax lignans Flax reduces the amount of DHT produced by reducing cholesterol levels in the body. A meta-analysis of 28 studies between 1990 and 2008 showed that flaxseed significantly reduces circulating total and LDL-cholesterol concentrations (Pan 2009). Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L (95% CI: -0.20, 0.00 mmol/L) and 0.08 mmol/L (95% CI: -0.16, 0.00 mmol/L), respectively. Significant reductions were observed with whole flaxseed (-0.21 and -0.16 mmol/L, respectively) and lignan (-0.28 and -0.16 mmol/L, respectively) supplements (Pan 2009).

References Angwafor F III, Anderson ML. An open label, dose response study to determine the effect of a dietary supplement on dihydrotestosterone, testosterone and estradiol levels in healthy males. J Int Soc Sports Nutr 2008;5:12.

Brzezińska-Wcisło L. Evaluation of vitamin B6 and calcium pantothenate effectiveness on hair growth from clinical and trichographic aspects for treatment of diffuse alopecia in women. Wiad Lek 2001;54:11-8.

Chittur S, Parr B, Marcovici G. Inhibition of inflammatory gene expression in keratinocytes using a composition containing carnitine, thioctic acid and saw palmetto extract. Evid Based Complement Alternat Med 2009.

Pan A, Yu D, Demark-Wahnefried W, Franco OH, Lin X. Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr 2009;90:288-97.

Prager N, Bickett K, French N, Marcovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia. J Altern Complement Med 2002;8:143-52.

Serenoa repens monograph. Alternative Medicine Review 1998;3:227-9.

Sinclair R. Male pattern androgenetic alopecia. BMJ 1998;317:865-9.

Sowmya P, Rajyalakshmi P. Hypocholesterolemic effect of germinated fenugreek seeds in human subjects. Plant Foods Hum Nutr 1999;53:359-65.

Stark A, Madar Z. The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on bile acid absorption and cholesterol levels in rats, Br J Nutr 1993;69:277-87.

Vierpper H, Nowotny P, Maier H, Waldhausl W. Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/ dilution and mass spectrometry. J Clin Endocrinol Metab 2001;86:5762-4.

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RESEARCH NEWS

Dietary carbohydrate restriction has metabolic advantages in liver disease

Effect of acupuncture depth on muscle pain

Individuals with nonalcoholic fatty liver disease (NAFLD) have excess intrahepatic triglycerides. Although weight loss is currently recommended to treat NAFLD, little attention has been given to dietary carbohydrate restriction. This study was undertaken to determine the effectiveness of two weeks of dietary carbohydrate and calorie restriction at reducing hepatic triglycerides in 18 subjects with NAFLD. Subjects consumed a carbohydraterestricted (<20 gram/day) or calorie-restricted (1200–1500 kcal/ day) diet for two weeks. Mean weight loss was similar between the groups. Liver triglycerides decreased significantly with weight loss (P < 0.001) but decreased significantly more (P = 0.008) in carbohydrate-restricted subjects than in calorie-restricted subjects. Dietary fat (r = 0.643, P = 0.004), carbohydrate (r = −0.606, P = 0.008), post-treatment plasma ketones (r = 0.755, P = 0.006), and respiratory quotient (r = −0.797, P < 0.001) were related to a reduction in liver triglycerides. Plasma aspartate, but not alanine, aminotransferase decreased significantly with weight loss (P < 0.001). The authors concluded that two weeks of dietary intervention (≈4.3% weight loss) reduced hepatic triglycerides by ≈42% in subjects with NAFLD but reductions were significantly greater with dietary carbohydrate restriction. Am J Clin Nutr.

2011 May;93(5):1048-52. PMID: 21367948

While evidence supports efficacy of acupuncture and/or dry needling in treating musculoskeletal pain, it is unclear which needling method is most effective. This study aimed to determine the effects of depth of needle penetration on muscle pain.

Twenty-two healthy volunteers performed repeated eccentric contractions to induce muscle soreness in their extensor digital muscle. Subjects were assigned randomly to four groups: control group, skin group (depth of 3mm: extensor digital muscle), muscle group (depth of 10mm: extensor digital muscle) and non-segmental group (depth of 10mm: anterior tibial muscle).

Pressure pain threshold (PPT) and electrical pain threshold (EPT) of the skin, fascia and muscle were measured at a point 20mm distal to the maximum tender point on the second day after the exercise. PPT of the skin group and muscle group were significantly higher than the control group, whereas EPT at fascia of the muscle group was significantly higher than the control group; however, there were no significant differences between the control and other groups. The authors concluded that acupuncture stimulation of muscle increases PPT and EPT of fascia and that the depth of needle penetration is important for the relief of muscle pain. Chin Med. 2011 Jun 22;6(1):24.

PMID: 21696603

Varenicline is associated with an increased risk of serious adverse cardiovascular events A systematic review and meta-analysis was conducted to ascertain the serious adverse cardiovascular effects of varenicline, a widely used smoking cessation drug. Double-blind, randomized controlled trials published through September 2010 (updated March 2011) of at least one week’s duration involving smokers or people who used smokeless tobacco were included. These studies reported on cardiovascular events (ischemia, arrhythmia, congestive heart failure, sudden death or cardiovascular-related death) as serious adverse events associated with the use of varenicline. Data from 14 trials, ranging from 7 to 52 weeks and that involved 8216 participants were analyzed. Varenicline was associated with a significantly increased risk of serious adverse cardiovascular events compared with placebo: 1.06% (52/4908) in the varenicline group versus 0.82% (27/3308) in the placebo group; Peto odds ratio (OR) 1.72, 95% confidence interval (CI) 1.09–2.71. Results of various sensitivity analyses were consistent with those of the main analysis and a no publication bias was detected. There were too few deaths to allow meaningful comparisons of mortality. This meta-analysis raises safety concerns about the potential for an increased risk of serious adverse cardiovascular events associated with the use of varenicline among tobacco users. CMAJ. 2011 Jul 4. PMID: 21727225

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RESEARCH NEWS

Iron deficiency in obesity is predicted by obesity-related inflammation rather than dietary iron intake Obese individuals may be at increased risk of iron deficiency (ID), but it is unclear whether this is due to poor dietary iron intakes or to adiposity-related inflammation. The current study investigated the relations between body mass index (BMI), dietary iron, iron status, and inflammation [C-reactive protein (CRP)]. Data from the 1999 Mexican Nutrition Survey, which included 1174 children and 621 nonpregnant women, were analyzed. The prevalence of ID was significantly higher in obese women and children compared with normal-weight subjects [odds ratios (95% CIs): 1.92 (1.23, 3.01) and 3.96 (1.34, 11.67) for women and children, respectively].

Despite similar dietary iron intakes in the two groups, serum iron concentrations were lower in obese women than in normal-weight women (P = 0.014) and total-iron-binding capacity was higher in obese children than in normal-weight children (P < 0.001). CRP concentrations in obese women and children were 4 times those of their normal-weight counterparts (P < 0.05) and CRP, but not iron intake, was a strong negative predictor of iron status (P < 0.05). The increased risk of ID in obesity may be due to the effects of obesityrelated inflammation on dietary iron absorption. Am J Clin Nutr.

2011 May;93(5):975-83. PMID: 21411619

Cortisol, energy intake, and food frequency in overweight/obese women This retrospective study investigated the relationship between daily urinary free cortisol excretion rate (as a marker of cortisol production rate) and daily caloric intake, food choice, body mass index (BMI), and waist circumference. One hundred twenty-seven overweight/obese women and 21 normal-weight subjects were enrolled in the study. Cortisol excretion rate was assessed using a 24-hour urine collection (UFC/24 h). In obese patients, the daily caloric intake was calculated, and a weekly food-frequency questionnaire was assessed. Results revealed that obese women had significantly higher UFC/24 h than the normal-weight women (P < 0.001). The obese subjects had an unbalanced diet, particularly rich in saturated lipids, and weekly food choice showed a preference for highly caloric foods. UFC/24 h values and waist circumference were significantly correlated (P < 0.001), regardless of BMI. In the obese group, the UFC/24 h values were also significantly and positively correlated to daily carbohydrate and lipid intake and to weekly starchy food consumption even after adjustment for BMI. This study demonstrated a significant association between higher UFC/24 h and energy intake, fats, and consumption of starchy foods, and that these relations were independent of BMI. Nutrition. 2011 Jun;27(6):677-80. PMID: 20934852

Dietary fructose may increase the risk of metabolic syndrome Excessive fructose intake may induce adverse metabolic effects but the effect of usual amounts of fructose intake on metabolic syndrome (MetS) is unknown. This cross-sectional population based study was conducted to determine the association of fructose intake and prevalence of MetS and its components. Subjects included 2537 participants of the Tehran Lipid and Glucose Study (45% men, aged 19-70 years). Dietary data were collected using a validated 168-item semi-quantitative food frequency questionnaire. Dietary fructose intake was calculated by sum of natural fructose in fruits and vegetables and added fructose in commercial foods.

Mean total dietary fructose intakes were 46.5+/-24.5 and 37.3+/-24.2 grams/day in men and women, respectively. Compared with those in the lowest quartile of fructose intakes, men and women in the highest quartile, respectively, had 33% (95% CI, 1.15-1.47) and 20% (95% CI, 1.09-1.27) higher risk of MetS; 39% (CI, 1.16-1.63) and 20% (CI, 1.07-1.27) higher risk of abdominal obesity; 11% (CI, 1.02-1.17) and 9% (CI, 1.02-1.14) higher risk of hypertension; and 9% (CI, 1-1.15) and 9% (1.04-1.12) higher risk of impaired fasting glucose.

The authors concluded that higher consumption of dietary fructose may have adverse metabolic effects. Nutr Metab (Lond). 2011 Jul 12;8(1):50. PMID: 21749680

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Bring your water to life NEW!

Ester-C® Energy Boost

Take the SISU Ester- C® Challenge and you could win a trip to your “Happy Place”!

1.800.663.4163 Visit estercchallenge.com or scan here for complete contest details.

Some restrictions apply.

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Ester- C and Ester - C logo are reg. TMs of The Ester C Company

For details, write #106 on Free Info Page, page 96.

• Daily, rehydrating vitamin drink mix - just add to water • Convenient “to go” packets - take to work, the gym, or use at home • 1,000 mg of Ester- C® vitamin C per serving • Ester- C® is non- acidic and increases white blood cell vitamin C levels for up to 24 hours • Enhanced with nourishing vitamins, minerals, and electrolytes

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SISU Ester-C® Energy Boost Monograph SISU Ester-C® Energy Boost

Active constituents: Each stick packet contains: Vitamin C 1000 mg, thiamine 0.38 mg, riboflavin 0.43 mg, niacinamide 5 mg, D-pantothenic acid 2.5 mg, vitamin B6 10 mg, vitamin B12 25 mcg, folic acid 30 mcg, zinc gluconate 2 mg, manganese 0.5 mg, chromium 10 mcg, magnesium 58 mg, phosphorus 160 mg.

General information: Ester-C® brand vitamin C: Ester-C® is a non-acidic form of vitamin C, in the form of calcium ascorbate. Ester-C® also contains vitamin C metabolites that improve its retention in cells.

Vitamin C in immune health: Vitamin C is highly concentrated in white blood cells and supports proper function of these cells. Although there has been ongoing controversy over whether vitamin C is helpful in the prevention of the common cold, the overall evidence suggests a benefit in reducing the duration and severity of symptoms and that those under stress (particularly significant physical stresses such as those associated with competitive sports) may reduce their risk of common cold by as much as 50% when vitamin C is used preventatively . In a randomized placebo controlled clinical trial, Ester-C® at a dose of 1000 mg per day for 60 days was found to significantly reduce the incidence and duration of common cold symptoms vs. placebo.

Vitamin C and tissue health: Vitamin C is required for the proper synthesis of collagen, the protein-based building block for much of the body’s tissues.

Vitamin C and anemia: In the prevention and treatment of iron deficiency, supplementing with at least 200 mg vitamin C per 30 mg of iron significantly improves iron absorption.

Vitamin C in cardiovascular health: A combination of vitamin C and vitamin E, over 6 years, has been shown to slow the progression of atherosclerosis in hypercholesterolemic men and women by 26-33%. 500 mg vitamin C can reduce CRP levels by 24% in those exposed to cigarette smoke (whether active or passive).

Peripheral arterial disease has been associated with both lower levels of vitamin C and higher levels of CRP. The antioxidant properties of vitamin C may also be helpful in the prevention of cardiovascular disease by helping to protect the arterial wall from oxidative damage. In addition, the importance of vitamin C in proper collagen synthesis may be beneficial in maintaining the health blood vessel walls.

Vitamin C in eye health: Long term (10 years or longer) use of supplemental vitamin C, either alone or in a multivitamin, has been associated with a 60% reduction in risk of nuclear and cortical cataracts. In combination with zinc, beta carotene and vitamin E, vitamin C has been found to significantly reduce the progression of age-related macular degeneration (AMD) and the loss of visual acuity in those with advanced AMD. The Ester-C® advantages Ester-C® has been shown to be less irritating to the GI tract of acid sensitive individuals than ascorbic acid. It remains in the white blood cells in higher concentration and for a longer period, and also has been shown to cause less ascorbic acid and oxylate output in the urine.

Doses and directions: Stir one packet into water or juice 1 to 2 times per day.

Therapeutic effects: Multivitamin/mineral supplement for the maintenance of good health.

Identity & Potency (per 9.2 g)

Quality Assurance Vitamin C (calcium ascorbate)

USP

1,000 mg

Riboflavin (riboflavin-5-phosphate)

USP

0.43 mg

Niacinamide

USP

5 mg

Pantothenic acid (calcium d-pantothenate)

USP

2.5 mg

Vitamin B6 (pyridoxine hydrochloride)

USP

10 mg

Thiamine (thiamine hydrochloride)

USP

0.38 mg

Folic acid (folate)

USP

30 mcg

Vitamin B12 (cyanocobalamin)

USP

25 mcg

Phosphorus (potassium phosphate)

USP

160 mg

Calcium (calcium ascorbate)

USP/ ICP

155 mg

Magnesium (magnesium carbonate, magnesium hydroxide)

USP/ ICP

58 mg

Zinc (zinc gluconate)

USP/ ICP

2 mg

Manganese (manganese gluconate)

USP/ ICP

0.5 mg

Chromium (chromium (III) polynicotinate)

USP/ ICP

10 mcg

References i ii

iii iv v

Cochrane Database Syst Rev. 2007 Jul 18;(3):CD000980 Van Sraten et al. Preventing the common cold with a vitamin C supplement: a double blind, placebo controlled survey.

Advances in Therapy; 2002 May;19(3):151-159.

J Circulation 2003 J Am Coll Nutr. 2004 Apr;23(2):141-7 Arch Ophthalmol. 2000 Nov;118(11):1556-63

sisu.com

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Arch Ophthalmol 2003;121:1621-4.

Gruenwald et al. 2006. Safety and tolerance of Ester C compared with regular ascorbic acid. Advances in Therapy.

23(1):Jan-Feb:171-8 viii Bernal et al. Vitamin C uptake in white blood cells in vivo. 2006. Unpublished ix Wright et al. A human clinical trial of Ester C vs. L-Ascorbic acid. 1987. vi

vii

1.800.663.4163

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RESEARCH NEWS

Even low to moderate sugar-sweetened beverages impair glucose and lipid metabolism and promote inflammation The following prospective, randomized, controlled crossover study was conducted to investigate the effects of small to moderate consumption of sugar-sweetened beverages (SSBs) for three weeks on glucose and lipid metabolism, and inflammatory markers in 29 healthy young men. Six 3-week interventions were assigned in random order as 1) dietary advice to consume low amounts of fructose or 600 mL SSBs containing 2) medium fructose (MF): 40 g fructose/day); 3) high fructose (HF): 80 g fructose/day; 4) medium glucose (MG): 40 g glucose/day; 5) high glucose (HG): 80 g glucose/day; and 6) high sucrose (HS): 80 g sucrose/day. Results revealed that LDL particle size was reduced after HF and HS (P < 0.05 for both) and a more atherogenic LDL subclass distribution was seen with fructose-containing SSBs (P < 0.05). Fasting glucose and high-sensitivity C-reactive protein increased significantly after all interventions (by 4–9% and 60–109%, respectively; P < 0.05) and leptin increased during interventions with glucose-containing SSBs (MG and HG: P < 0.05). This study shows potentially harmful effects of low to moderate consumption of SSBs on markers of cardiovascular risk within just three weeks in healthy young men.

Am J Clin Nutr. 2011 Aug;94(2):479-85. PMID: 21677052

Short sleep duration increases energy intake but not energy expenditure Evidence suggests that there is a relationship between short sleep duration and obesity so the current study assessed energy balance during periods of short and habitual sleep. Fifteen men and 15 women aged 30–49 years with a body mass index of 22–26 kg/m2 who regularly slept 7–9 hours/night participated in this crossover study. Participants were studied under short (4 hour/night) and habitual (9 hour/night) sleep conditions, in random order, for five nights each. Food intake was measured on day five, and energy expenditure was measured with the doubly labeled water method over each period. Participants consumed more energy on day five during short sleep than during habitual sleep (P = 0.023) and this effect was mostly due to increased consumption of fat (P = 0.01), notably saturated fat (P = 0.038).

Resting metabolic rate and total energy expenditure did not differ significantly between sleep phases. These data show that a reduction in sleep increases energy and fat intakes, which may explain the associations observed between sleep and obesity. If sustained and not compensated by increased energy expenditure, the dietary intakes of individuals undergoing short sleep predispose to obesity. Am J Clin Nutr. 2011 Aug;94(2):410-6.

PMID: 21715510

Serum phosphate levels are associated with aortic valve sclerosis and annular calcification Mineral metabolism disturbances are common among older people and may contribute to cardiac valvular calcification. The current study was conducted to evaluate mineral metabolism markers as potential risk factors for calcific aortic valve disease. Serum levels of phosphate, calcium, parathyroid hormone, and 25-hydroxyvitamin D were measured in 1938 Cardiovascular Health Study participants who were free of cardiovascular disease and who underwent echocardiographic measurements of aortic valve sclerosis (AVS), mitral annular calcification (MAC), and aortic annular calcification (AAC). The respective prevalences of AVS, MAC, and AAC were 54%, 39%, and 44%. Each 0.5 mg/dl higher serum phosphate concentration was associated with greater adjusted odds of AVS (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.04 to 1.31, p = 0.01), MAC (OR: 1.12, 95% CI: 1.00 to 1.26, p = 0.05), and AAC (OR: 1.12, 95% CI: 0.99 to 1.25, p = 0.05). Serum calcium, parathyroid hormone, and 25-hydroxyvitamin D concentrations were not associated with aortic or mitral calcification. Therefore, phosphate may be a novel risk factor for calcific aortic valve disease as higher serum phosphate levels within the normal range were associated with valvular and annular calcification. J Am Coll Cardiol. 2011 Jul 12;58(3):291-7. PMID: 21737022

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Intestinal Therapy Repairing damage to the intestinal lining

By Brenda Watson According to The Crohn’s and Colitis Foundation of Canada over 200,000 Canadian men, women and children have Inflammatory Bowel Disease (Crohn’s and ulcerative colitis) (Jan 25, 2011). Many practitioners have found it difficult to find an effective treatment for their patients. Patients often become desperate as their disorders are not only physically painful, but can wreak havoc on their personal and professional lives as well.

The intestinal disorders listed above have similar symptoms; one of these similarities is that there has been some form of damage to the intestinal lining. For example: “Research done in 2002 confirms that in Crohn’s disease, the protective lining in the gut becomes more permeable than usual, which allows potentially harmful substances to pass through. CD researchers have thought that a defect in the gut barrier that allows harmful substances to pass through it could cause the disease by triggering an immune response that sets off chronic inflammation in the gut but the literature is unclear whether the leaky gut in Crohn’s patients precedes inflammation or is a consequence of it” (Canadian Society for Intestinal Research cited Jan 22/2010).

What is well know is that the intestinal tract lining is vital to the overall health and well-being of all patients, as this is where nutrients are absorbed. The intestinal wall secretes mucus which forms a ‘lining’ that covers the surface of the intestinal tract. This lining is essential for proper digestion, immune function and overall health. The intestinal lining has many important functions including: 1.

2.

3.

Lubricating intestinal contents.

Helping with nutrient absorption by allowing properly digested nutrients into the bloodstream.

Serving as a protective barrier to prevent the absorption of toxins, bacteria, parasites and undigested foods from moving from the digestive tract into the bloodstream.

The function of the mucous lining of the small intestine has been compared to that of a window screen, which lets air in but keeps bugs out. It also has similarities to the skin, in that it sloughs off a layer of cells naturally every 3 to 5 days and produces new cells to keep the lining semi-permeable. This regeneration process is what happens in those with a healthy intestinal lining; however this is not always the case for those with intestinal disorders.

Currently it is unknown what causes the disruption of the intestinal lining regeneration process, but regardless a porous and incomplete lining can cause many problems. Some possible factors leading to the disruption include impaired digestion by stress, processed food consumption, inadequate chewing, excessive fluid intake with meals, improper food combining and overeating. All of these factors have been thought to lead to a permeable (leaky) gut. In fact some practitioners have used the terms ‘Leaky Gut’ and ‘Leaky Gut Syndrome’ to describe this condition.

One theory is that when bacteria in the intestine act upon undigested food particles, toxic chemicals and gases are produced. These intestinal toxins can damage the mucosal lining, resulting in increased intestinal permeability. Other factors that may cause or aggravate intestinal permeability include:

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o

Alcohol

o

Antacids

o

Antibiotics (which lead to overgrowth of bad bacteria in the GI tract)

o

Bacteria

o

Birth control pills

o

Caffeine

o

Chemical food additives

o

Diet of refined carbohydrates

o

Enzyme deficiencies (as found in celiac disease and lactose intolerance)

o

Free radicals

o

Heightened exposure to environmental toxins

o

Mold and fungal mycotoxins

o

NSAIDS

o

Parasites

o

Steroids (includes prescription corticosteroids such as prednisone and hydrocortisone)

o

Stress

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If the intestinal lining becomes porous to the extent that some of the contents passing through the intestines are allowed to enter the bloodstream, then problems are very likely to occur. Food particles would not be the only things able to slip through. Pathogens and toxins which would normally be screened out could also end up throughout the body. The insufficiently broken-down food particles or toxins may cause the liver to work overtime. If the liver is not able to keep up with the extra detoxification processes, then toxic load will build up in the body. If not removed right away, the toxins can move through the system and settle into any tissue they pass by, leading to the possibility of inflammation.

When the intestines are porous, any food eaten and inadequately digested could end up in the bloodstream, leading to food intolerances.

If a patient has food sensitivities to more than a dozen foods, it is very possible that they have a leaky gut. The best way to test for food sensitivities is through a food trial. A leaky gut should be considered in cases where previously tolerated foods begin to cause problems, after the sensitive foods have already been removed from a patientâ&#x20AC;&#x2122;s diet. It is possible that the underling cause may not be the foods they are eating, but that they have poor digestion and a porous intestine, therefore anything frequently eaten may become an issue.

What are the Signs and Symptoms of Leaky Gut Syndrome? o o o o o

Eczema Food Allergies I.B.S. (Irritable Bowel Syndrome) Multiple chemical sensitivities Psoriasis

Leaky gut syndrome can aggravate existing conditions as well such as: o o o o o o o o

abdominal discomfort diarrhea fatigue joint pain memory deficit muscle pain shortness of breath skin rashes

Healthy Intestinal Lining

Leaky gut syndrome can also cause malabsorption of important nutrients â&#x20AC;&#x201C; vitamins, minerals and amino acids, eventually leading to complaints such as: o o o o o

fatigue headaches irritability memory loss poor concentration

Unhealthy Intestinal Lining

How to test for a leaky gut Provide an Intestinal Permeability Assessment for your patient. An intestinal permeability assessment analyzes urine for the clearance of two non-metabolized sugars, lactulose and mannitol; which identify leaky gut syndrome and malabsorption. Although the body cannot metabolize mannitol and lactulose, if digestion is functioning properly, mannitol, because it is a small molecule, will readily be absorbed across the gut wall, while lactulose will be poorly absorbed due to the fact that it is a large molecule.

After ingesting a liquid containing a mixture of the two sugars, if the urine shows high levels of mannitol and low levels of lactulose, it is an indicator that food is being properly absorbed. When levels of both sugars are high, leaky gut syndrome is indicated. Low levels of both sugars would be indicative of general malabsorption of nutrients, while low mannitol, along with high lactulose, has been found in people with inflammatory bowel disease and celiac disease (Johnston et al 2001 and Watson & Smith, 2003).

So what can be done for a patient with a suspected leaky gut?

The first thing to look at is what constitutes a properly functioning intestinal tract. A healthy functioning intestinal tract will replace its cells roughly two times per week. In order to replace intestinal lining cells, two of the main nutrients required to rebuild the intestinal mucosa are L-Glutamine and N-acetyl glucosamine. L-Glutamine has been shown to increase intestinal villous height and stimulate mucosal cell growth in the intestinal tract (Miller, 1999) while N-acetyl glucosamine, is required for tissue repair mechanisms (Salvatore et al, 2000).

Therefore it makes sense to provide the body with a therapeutic dose of L-Glutamine as well as N-Acetyl-Glucosamine to heal the damaged areas of the intestinal tract lining.

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The practitioner brand Advanced Naturals has a product called Intestinal Therapy that does just that. Each serving provides 5000 mg of L-Glutamine and 200 mg of N-Acetyl D-Glucosamine. It also includes ingredients to soothe the intestinal tract lining as well as ingredients to help to reduce inflammation, and to reduce diarrhea. These include: • • • •

Ginger Root which has anti-inflammatory properties, as well as carminative properties which help to expel gas from the stomach and intestines.

Marigold Flower which helps to alleviate mucous membrane inflammation.

Marshmallow root has demulcent properties which help to alleviate local irritation and inhibits mucociliary activity.

Gamma Oryzanol enhances gastric & illeal movement.

Intestinal Therapy has been approved by Health Canada’s Natural Health Product Directorate to repair and maintain a healthy intestinal tract lining and has been given the NPN number 80002822.

Dosage: Powder: Take one scoop of Intestinal Therapy powder mixed with water in the morning on an empty stomach.

Capsules: Take 7 capsules with water in the morning on an empty stomach.

According to Brenda Watson and Dr. Leonard Smith MD the amounts can be increased in regards to the severity of the condition. For instance those with chronic cases of Crohn’s or Colitis can take up to 20,000mg of L-Glutamine (2 scoops of Intestinal Therapy powder twice per day) under the care of their registered health care practitioner.

Conditions which can benefit from Intestinal Therapy Although the focus of this article has been on leaky gut and ongoing disorders such as Crohn’s and Colitis, there are many other conditions which can benefit from Intestinal Therapy including those who have had parasites, or bacterial infections. Celiac’s disease patients, even including those who have been on a gluten-free diet for over a year, can benefit as their intestinal permeability has been shown to be higher than the average.

Intestinal Therapy helps the body to repair and maintain a healthy intestinal tract lining, while also helping to reduce inflammation in the intestinal tract.

Those that suffer from leaky gut syndrome, poor intestinal health, Irritable Bowel Syndrome, Colitis and Crohn’s disease should see an improvement in symptoms within 30 days of taking Intestinal Therapy. Those with ongoing disorders such as Colitis and Crohn’s can continue to take it on a regular basis if needed. Some patients have found after the first month that taking a ½ dose everyday is often enough.

To purchase Advanced Naturals products call 1-800-485-0960 Ext. 6 or visit our website at www.advancednaturals.ca.

REfERENCES: American Botanical Council. Expanded Commission E Monographs, Therapeutic Guide To Herbal Medicine. [Internet]. [cited 2011 Jan 15]. Available from: http://cms.herbalgram.org/ commissione/Monographs.html Bourlioux, P., Koletzko, B., Guarner, F., Braesco, V. (2003) “The intestine and its microflora are partners for the protection of the host: report on the Danone Symposium “The Intelligent Intestine,” held in Paris, June 14, 2002” American Journal of Clinical Nutrition, Vol. 78, No. 4, 675-683, October.

Canadian Society of Intestinal Research. Anti-TFN-a Treatment Restores Gut Barrier [Internet]. [cited 2011 Jan 23]. Available from: http://www.badgut.org/information-centre/anti-tfn-a-treatment-1.html/?searchterm=gut.

The Crohn’s and Colitis Foundation of Canada. Crohn’s & Colitis. [Internet]. [cited 2011 Jan 25]. Available from: http://www.ccfc.ca/English/info/index.html Grzanna R, Lindmark L, Frondoza CG. (2005). Ginger--an herbal medicinal product with broad anti-inflammatory actions. J Med Food. Summer;8(2):125-32.

Johnston SD, Smye M, Watson RP. (2001). Intestinal permeability tests in coeliac disease. Clin Lab. 47(3-4):143-50.

Miller, Alan L. (1999). Therapeutic Considerations of L-Glutamine: A Review of the Literature Alternative Medical Review Aug;4(4):239-48.

Salvatore, S., Heuschkel, R., Tomlin, S., Davies, S.E., Edwards, S., Walker-Smith, J.A., French, I., Murch, S.H. (2000). A Pilot Study of N-Acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. Dec;14(12); 1567-79.

Vilela EG, Torres HO, Ferrari ML, Lima AS, Cunha AS. (2008). Gut permeability to lactulose and mannitol differs in treated Crohn’s disease and celiac disease patients and healthy subjects. Braz J Med Biol Res. Dec;41(12):1105-9.

Watson, B. & Smith L. (2003) Gut Solutions, Clearwater, Florida: Renew Life Press and Information Service 6-7, 128, 153-158, 223

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Product composition Medicinal Ingredients: Each scoop (5.4g) contains: Glutamine .......................................................................5,000 mg N-Acetyl-Glucosamine .....................................................200 mg Gamma oryzanol ...............................................................125 mg Cranesbill root (Geranium maculatum) .........................18.75 mg Ginger root (Zingiber officinale) ...................................18.75 mg Marigold flower (Calendula officinalis) ........................18.75 mg Marshmallow root (Althea officinalis) ..........................18.75 mg Non-medicinal ingredients: None Recommended dose: Adults: 1 scoop per day, mixed in water, in the morning on an empty stomach.

Duration of use: Consult a health care practitioner for use beyond 6 weeks.

Indication: Supports a healthy intestinal lining.

Contraindications: Do not use if pregnant, breastfeeding, or are sensitive to the Asteraceae/Compositae family of plants (i.e.

Marigold). Do not exceed recommended dose.

Warnings: Keep out of reach of children.

Precautions: Discontinue use if abdominal pain, nausea, or vomiting occurs unless otherwise directed by a physician. Consult your physician prior to use if you have a serious medical condition, kidney disease, or are following a low protein diet.

Adverse Effects: None.

Overdose: For management of suspected product overdose it is recommended to contact your physician. If unavailable, seek emergency assistance.

Symptoms of Overdose: Has not been investigated nor any reports have been filed.

Supporting Research and Traditional Evidence Glutamine (L-Glutamine) L-Glutamine is a dispensable amino acid and following ingestion it is metabolized mainly in the splanchnic tissues. Following absorption it is metabolized to citrulline, arginine, glutamate, and proline.

(Reeds, 2001). Glutamine is quantitatively the most important fuel for intestinal tissue. It is metabolized to L-alanine by a route involving conversion to glutamate, then 2-oxoglutarate via glutaminase and glutamate dehydrogenase respectively, then tricarboxylic acid cycle conversion to malate (2-oxoglutarate, succinate, fumarate and finally malate) followed by the action of NADP+- dependent malic enzyme to create pyruvate which undergoes amination to produce L-alanine via the action of alanine transaminase (Newsholme, 2003). Other areas of metabolism of Glutamine also occur in the liver, kidneys and lymphocytes.

Endogenous metabolism of Glutamine synthesis also occurs in muscle, intestine and brain (LSRO, 1992). Endogenous production in an adult is estimated to be 60-100 g per day (van Acker, 1999).

Glutaminase and glutamine synthetase are the two primary enzymes responsible for glutamine metabolism.

Numerous studies evaluated safety of orally ingested glutamine at doses of 0.3g/kg of body weight and intravenous infusions of glutamine at doses up to 0.025 g/kg body weight/hour. Effects of total parenteral nutrition were also conducted at doses of 0.57g/kg body weight per day over duration of 5 days. Results indicated that at a single oral dose of glutamine the plasma glutamine concentrations rose twofold after 1 hour and returned to basal levels within 4 hours.

In the total parenteral nutrition there was no evidence of neurotoxicity and none of the other studies revealed any adverse effects at any dose via oral or intravenous administration (Ziegler, 1990).

A number of other studies have also been performed using high doses of glutamine and similarly no notable significant adverse effects have been reported (IOM, 2002).

The intestines primary role is of digestion, nutrient absorption and fermentation. In addition new evidence is pointing to itâ&#x20AC;&#x2122;s role in more

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complex roles of such as immune surveillance and in generating endocrine responses to the luminal environment (Burrin,2000).

Supplemental glutamine administration has two primary potential implications on intestinal health. First, by influencing the synthesis of components of the extracellular matrix, glutamine may be one important factor in the mucosal structure and in particular the maintenance of tight junctions (Panigrahi, 1997). Secondly, glutamine may be a potential precursor for N-acetylglucosamine and N-acetylgalactosamine synthesis. Glutamine may play an important role in intestinal mucin synthesis and hence the maintenance of passive barrier to bacterial ingress (Khan, 1999).

Specific clinical studies by Peng, 2004 have shown that 0.5 g/kg of glutamine granules administered to severe burn patients abated the degree of intestinal injury, reduced intestinal mucosal permeability, ameliorated wound healing and reduced hospital stay. A study performed by Noyer, 1998 on AIDS patients examined abnormal intestinal permeability and showed a trend towards intestinal permeability improvements in this subpopulation at a daily dose of 4g or 8g per day. Authors of the study suggested that a dose of 20g glutamine may be necessary to see significant effects. Yoshida, 1998 evaluated the use of glutamine supplementation in 13 patients with esophageal cancer undergoing radiochemotherapy. Glutamine was administered orally at a dose of 30 g/day at the start of radiochemotherapy and for the subsequent 28 days. Results indicated that oral glutamine supplementation protects lymphocytes and attenuates gut permeability in patients with esophageal cancer during radiochemotherapy. Lastly, a study performed by van der Hulst, 1993 showed administration of glutamine via parenteral feeding prevented the deterioration of gut permeability and preserved mucosal structure.

N-acetyl glucosamine (2-Acetamido-2-deoxy-alpha-glucopyranose) Glucosamine is an amino-monosaccharide naturally produced in humans. N-acetyl glucosamine is an amide of glucosamine and acetic acid and is one of the principal substrates used in the biosynthesis of macromolecules that comprise articular cartilage, such as glycosaminoglycans, proteoglycans, and hyaluronic acid. Upon oral ingestion glucosamine is absorbed from the small intestine (Setnikar, 1993). A small scale evaluation of N-acetyl glucosamine and polymeric form of N-acetyl glucosamine suggests that it is readily absorbed with the polymeric form, producing sustained levels (Talent, 1996).

A small scale pilot study conducted by Salvatore, 2000 in 12 children evaluated the effects of N-acetyl glucosamine as an adjunct therapy in treating inflammatory bowel disease. Enrolled subjects were diagnosed with refractory inflammatory bowel disease, Crohnâ&#x20AC;&#x2122;s disease and/or ulcerative colitis. Every subject was administered 3-6g/day N-acetyl glucosamine. Results showed that eight children of the twelve demonstrated clear improvements indicating that N-acetyl glucosamine is a strong candidate for reducing inflammatory conditions of the intestinal lining.

Gamma oryzanol Gamma oryzanol is defined as a mixture of ferulic acid esters of sterol and triterpene alcohols. This mixture occurs in rice bran oil typically at a level of 1-2% (Scavariello, 1998).

A number of clinical trials suggest that gamma oryzanol may be helpful for people with gastritis and other gastrointestinal complaints.

In a study by Maruyama, 1976, twenty two subjects with chronic gastritis were orally administered 300mg/day gamma oryzanol. After two weeks, five subjects reported that gamma oryzanol was extremely effective and twelve said it was moderately effective. An average of 87% of subjects experienced some benefit from supplementation. In another study, eighteen subjects with varying types of gastritis also received 300mg/day gamma oryzanol (Kamiji, 1976). Following two week supplementation more than 62% of those with superficial gastritis and over 87% with atrophic gastritis benefited. A large scale hospital study conducted by Takemoto, 1977 recruited approximately two thousand subjects with varying gastrointestinal complaints, including gastritis. Enrolled

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subjects were given approximately 100mg gamma oryzanol three times daily. Some individuals were required to ingest as much as 600mg/day before improvements in symptoms were noted. Duration of the study ranged from less than a month up to 275 days for some subjects.

acid and sterols (Gudej, 1991). Traditionally, marshmallow root has been effectively used for gastro-enteritis, peptic and duodenal ulceration, common and ulcerative colitis and enteritis and is stated to poses demulcent, emollient and anti-inflammatory properties (Bradley, 1992).

Cranesbill (Geranium maculatum) root Geranium root chemically contains a large proportion of tannins (10%-28%) of the hydrolysable type most likely including geraniin (Hajkova, 1964). Traditionally Geranium maculatum has been used internally for peptic and duodenal ulcers (Bradley, 2006). It has been reported that when duodenal or gastric ulceration is associated with bleeding, this herb may be used in combination with other relevant herbs to combat the condition. Additionally, geranium provides astringent, anti-inflammatory and vulnerary properties (Hoffmann, 2003).

Ingredient Summary Glutamine •Supports a healthy intestinal lining.

N-acetyl glucosamine •May reduce inflammatory conditions of the intestinal lining.

Gamma oryzanol •May help with reductions of complaints associated with gastritis.

Cranesbill root (Geranium maculatum) •Traditionally used for peptic and duodenal ulcers.

Ginger root (Zingiber officinale) •Traditionally used to relieve digestive upset and disturbances including lack of appetite, nausea, digestive spasms, indigestion, dyspepsia and flatulent colic.

Marigold flower (Calendula officinalis) •Traditionally used for complaints of the digestive system such as gastric and duodenal ulcer, gastritis and colitis.

Marshmallow root (Althea officinalis) •Traditionally used for gastro-enteritis, peptic and duodenal ulceration, common and ulcerative colitis and enteritis.

Ginger (Zingiber officinale) root Constituents of ginger known for its “pungent principles” or non-volatile constituents are considered responsible for its pharmacological activity. These include: gingerols including (6)-gingerol (usually <1% of the root's weight) (Wang, 2005), (6)-shagaol (a dehyroxylated analog of (6)-gingerol), (6)- and (10)-dehyro-gingerdione, (6)- and (10)-gingerdione, (6)-paradol, vallinoids, galanals A and B, and zingerone (Surh, 1999). Ginger finds wide spread use in many of the world’s traditional medicinal systems. Traditionally, this use has been for disorders of the gastrointestinal tract, as a stomachic, laxative, sialogogue, gastric emptying enhancer, appetizer, antiemetic, and antidyspepsic and, at the same time, as an antidiarrheal and anticolic agent (Ghayur, 2005; Nadkarni, 1976). Specifically in Western Traditional Herbal Medicine ginger has been well documented to help relieve digestive upset and disturbances including lack of appetite, nausea, digestive spasms, indigestion, dyspepsia and flatulent colic (NHPD, 2009).

Clinical research has shown ginger to be effective in accelerating gastric emptying and stimulation of antral contractions in healthy volunteers when subjects were administered 1200mg/day ginger (Wu, 2008). A study by Micklefield, 1999 confirmed these results by showing that two doses of 100mg ginger rhizome extract also improved gastroduodenal motility after a test meal in twelve healthy volunteers. The pharmacological basis for the medicinal use of ginger in gastrointestinal disorders has been studied in animal models (Ghayur, 2005). Prokinetic activity of ginger extract was confirmed in an invitro test when it enhanced the intestinal travel of charcoal meal in mice. Ginger extract also showed an atropine-sensitive dose-dependent spasmogenic effect in vitro as well as in isolated rat and mouse stomach fundus tissues. In atropinized tissue, it showed spasmolytic activity as shown by the inhibition of 5-HT- and K+-induced contractions. The results of the study showed that ginger extract contains cholinergic, spasmogenic component evident in stomach fundus preparations which support a mechanistic explanation for the prokinetic action of ginger.

Marigold (Calendula officinalis) flower The primary identified constituents of marigold are triterpenoids and flavonoids (Yoshikawa, 2001; Vidal-Ollivier, 1989). At least eight bioactive triterpendiol monoesters have been found in Marigold flowers: faradiol-3-O-palmitate, faradiol-3-O-myristate, faradiol-3-O-laurate, arnidiol-3-O-palmitate, arnidiol-3-O-myristate, arnidiol-3-O-laurate, calenduladiol-3-O-palmitate, and calenduladiol3-O-myristate (Neukirch, 2004). Triterpenoids and in particular faradiol monoesters are suspected to be responsible for marigold’s anti-inflammatory effects (Della, 1990; Della, 1994).

Experiments in cell-free systems with marigold extracts showed inhibitory activity of 5-lipoxygenase (5-LO) and cyclooxygenase-2 (COX-2) which are key enzymes involved in inflammatory pathways further suggesting the possible mechanisms of action (Bojadjiev, 1964). Based on traditional medicines, marigold flower has been stated to posses anti-inflammatory and gastroprotective properties.

Traditionally it has been used internally for inflammatory complaints of the digestive system such as gastric and duodenal ulcer, gastritis and colitis (Bradley, 2006).

Marshmallow (Althea officinalis) root Marshmallow root contains mucilage polysaccharides typically found at 6.2%-11.6% concentration. These polysaccharides are composed of galacturonorhamnans, arabinans, glucaris and arabinogalactans.

Other constituents typically found are carbohydrates, flavanoids, glycosides, sugars, amines, fat, calcium oxalate, coumarins, phenolic

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2.Bradley P. British Herbal Compendium. Vol. II. Bournemouth: British Herbal Medicine Association; 2006.

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4.Burrin DG, Stoll B, Jiang R, Chang X, Hartmann B, Holst JJ, Greeley GH Jr, Reeds PJ. Minimal enteral nutrient requirements for intestinal growth in neonatal piglets: how much is enough? Am J Clin Nutr. 2000 Jun;71(6):160310.

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6.Della Loggia R., Tubaro, A., Sosa, S., Becker, H., Saar, S., and Isaac, O. The role of triterpenoids in the topical anti-inflammatory activity of Calendula officinalis flowers. Planta Med 1994;60(6):516-520.

7.Ghayur MN, Gilani AH: Ginger: from myths to reality. In Handbook of Ethnotherapies. CE Gottschalk, JC Green (eds). Hamburg, Verlag und Vertrieb, 2005 8.Ghayur MN, Gilani AH. Pharmacological basis for the medicinal use of ginger in gastrointestinal disorders. Dig Dis Sci. 2005 Oct;50(10):1889-97.

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14.Kamiji M, et al. [Practical usage of gamma-oryzanol on indefinite complaints of digestive system.] [Article in Japanese] Shinyaku To Rinsho 1976;25:136 15.Khan J, Iiboshi Y, Cui L, Wasa M, Sando K, Takagi Y, Okada A. Alanyl-glutamine-supplemented parenteral nutrition increases luminal mucus gel and decreases permeability in the rat small intestine. JPEN J Parenter Enteral Nutr. 1999 Jan-Feb;23(1):24-31.

16.LSRO (Life Sciences Research Office). 1992. Safety of Amino Acids Used as Dietary Supplements. Bethesda, MD: LSRO. 17.Maruyama K, et al. [Usefulness of Hi-Z fine granule (gamma-Oryzanol) for the treatment of autonomic instability in gastrointestinal system.] [Article in Japanese]. Shinyaku To Rinsho 1976;25:124 18.Micklefield GH, Redeker Y, Meister V, Jung O, Greving I, May B. Effects of ginger on gastroduodenal motility.

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19.Nadkarni KM: Zingiber officinale. In Indian Materia Medica. Bombay, Popular Prakashan, 1976, pp 1308–1315 20.Neukirch H, D'Ambrosio M, Dalla Via J, Guerriero A. Simultaneous quantitative determination of eight triterpenoid monoesters from flowers of 10 varieties of Calendula officinalis L. and characterisation of a new triterpenoid monoester. Phytochem Anal. 2004 Jan-Feb;15(1):30-5.

21.Newsholme P, Procopio J, Lima MM, Pithon-Curi TC, Curi R. Glutamine and glutamate-their central role in cell metabolism and function. Cell Biochemistry and Function 2003;21(1):1-9.

22.NHPD Ginger Monograph. http://www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/licenprod/monograph/mono_ginger-gingembre-eng.php 23.Noyer CM, Simon D, Borczuk A, Brandt LJ, Lee MJ, Nehra V. A double-blind placebo-controlled pilot study of glutamine therapy for abnormal intestinal permeability in patients with AIDS. Am J Gastroenterol. 1998 Jun;93(6):972-5.

24.Panigrahi P, Gewolb IH, Bamford P, Horvath K. Role of glutamine in bacterial transcytosis and epithelial cell injury. JPEN J Parenter Enteral Nutr. 1997 Mar-Apr;21(2):75-80.

25.Peng X, Yan H, You Z, Wang P, Wang S. Effects of enteral supplementation with glutamine granules on intestinal mucosal barrier function in severe burned patients. Burns. 2004 Mar;30(2):135-9.

26.Reeds PJ, Burrin DG. 2001. Glutamine and the bowel. J Nutr 131:2505S–2508S. 27.Salvatore S, Heuschkel R, Tomlin S, Davies SE, Edwards S, Walker-Smith JA, French I, Murch SH. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000 Dec;14(12):1567-79.

28.Scavariello, EM, Arellano, DB. [Gamma-oryzanol: an important component in rice brain oil.] [Article in Spanish] Arch Latinoam.Nutr 1998;48(1):7-12.

29.Setnikar, I., Palumbo, R., Canali, S., and Zanolo, G. Pharmacokinetics of glucosamine in man.

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30.Shils ME, Olson JA, Shike M, Ross AC, editors. Modern Nutrition in Health and Disease, 10th edition.

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31.Surh Y, Park K, Chun K, and et al. Anti-tumor-promoting activities of selected pungent phenolic substances present in ginger. Journal of Environmental Pathology, Toxicology and Oncology 1999;18(2):131-139.

32.Takemoto T, et al. [Clinical trial of Hi-Z fine granules (gamma-oryzanol) on gastrointestinal symptoms at 375 hospitals (Japan).] [Article in Japanese] Shinyaku To Rinsho 1977;26 33.Talent JM, Gracy RW. Pilot study of oral polymeric N-acetyl-D-glucosamine as a potential treatment for patients with osteoarthritis. Clin Ther. 1996 Nov-Dec;18(6):1184-90.

34.van Acker BA, von Meyenfeldt MF, van der Hulst RR, Hulsewé KW, Wagenmakers AJ, Deutz NE, de Blaauw I, Dejong CH, van Kreel BK, Soeters PB. 1999. Glutamine: The pivot of our nitrogen economy? JPEN J Parenter Enteral Nutr. 1999 Sep-Oct;23(5 Suppl):S45-8.

35.van der Hulst RR, van Kreel BK, von Meyenfeldt MF, Brummer RJ, Arends JW, Deutz NE, Soeters PB. Glutamine and the preservation of gut integrity. Lancet. 1993 May 29;341(8857):1363-5.

36.Vidal-Ollivier E, Elias R, Faure F, Babadjamian A, Crespin F, Balansard G, Boudon G. Flavonol Glycosides from Calendula officinalis Flowers. Planta Med. 1989 Feb;55(1):73-4.

37.Wang, W. H. and Wang, Z. M. [Studies of commonly used traditional medicine-ginger]. [Article in Chinese] Zhongguo Zhong.Yao Za Zhi. 2005;30(20):1569-1573.

38.Wu KL, Rayner CK, Chuah SK, Changchien CS, Lu SN, Chiu YC, Chiu KW, Lee CM. Effects of ginger on gastric emptying and motility in healthy humans. Eur J Gastroenterol Hepatol. 2008 May;20(5):436-40.

39.Yoshida S, Matsui M, Shirouzu Y, Fujita H, Yamana H, Shirouzu K. Effects of glutamine supplements and radiochemotherapy on systemic immune and gut barrier function in patients with advanced esophageal cancer. Ann Surg. 1998 Apr;227(4):485-91.

40.Yoshikawa, M., Murakami, T., Kishi, A., Kageura, T., and Matsuda, H. Medicinal flowers. III. Marigold. (1): hypoglycemic, gastric emptying inhibitory, and gastroprotective principles and new oleanane-type triterpene oligoglycosides, calendasaponins A, B, C, and D, from Egyptian Calendula officinalis. Chem Pharm Bull (Tokyo) 2001;49(7):863-870.

41.Ziegler TR, Benfell K, Smith RJ, Young LS, Brown E, Ferrari-Baliviera E, Lowe DK, Wilmore DW. 1990. Safety and metabolic effects of L-glutamine administration in humans. J Parenter Enteral Nutr 14:137S–146S.

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INDUSTRY NEWS Low magnesium levels can be associated with longterm use of Proton Pump Inhibitor drugs The U.S. Food and Drug Administration (FDA) is informing the public that prescription proton pump inhibitor (PPI) drugs may cause low serum magnesium levels if taken for prolonged periods of time (i.e., longer than one year). In approximately one-quarter of the cases reviewed, magnesium supplementation alone did not improve low serum magnesium levels and the PPI had to be discontinued. In contrast to prescription PPIs, over-thecounter (OTC) PPIs are marketed at low doses and are only intended for a 14 day course of treatment up to three times per year. The FDA believes that there is very little risk of hypomagnesemia when OTC PPIs are used according to the directions on the OTC label. Low serum magnesium levels can result in serious adverse events including tetany, arrhythmias, and seizures.

The FDA urges healthcare professionals to obtain serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics, or other drugs that may cause hypomagnesemia.

SickKids app helps patients manage IBD The Hospital for Sick Children in Toronto has launched a free mobile app to empower people with Inflammatory Bowel Disease (IBD) to take control of the disease. myIBD app allows patients to track their food, stool, pain and frequency of washroom visits all on mobile devices. The app offers a visual tracking system so patients can monitor their disease activity and seek help when necessary in an effort to avoid flare-ups and hospital admissions. “We support our patients and their families as they adjust to the lifestyle changes required to effectively manage IBD, whether it be diet and lifestyle changes, medication, or simply monitoring symptoms. The app provides patients with immediate, round-

the-clock access to current, reliable and educational IBD information to supplement the information they get in the clinic,” says Karen Frost, one of the Project Leaders and IBD Nurse Practitioner at SickKids.

“With education comes a good foundation for long term remission of disease. We stick to our mantra that ‘remission is the mission’.” myIBD app is currently available for free in the App Store for iPhones, iPad, and the iPod touch. It will also be available to Android devices later this year.

Possible link between Finasteride and male breast cancer Health Canada reports that male breast cancer has been reported in a small number of patients worldwide taking the prescription drug finasteride for male pattern baldness and enlarged prostate.

Finasteride is sold under two brand names in Canada, Propecia (1 mg) to treat male-pattern hair loss and Proscar (5 mg), which is used for benign prostatic hyperplasia. Generic versions of both are also sold. Male breast cancer has been reported with both the 1 mg and 5 mg formulations of finasteride but most of the reports have been in association with the 5mg formulation. Based on the currently available evidence, it is not known with certainty whether finasteride can cause breast cancer, nor can this possibility be ruled out at this point in time. The labeling for Propecia, Proscar and several of the generic finasteride products has already been updated to include information on the potential risk of male breast cancer.

Updates to the remaining generic drugs will follow. Healthcare professionals should encourage their patients taking finasteride to report any changes in their breasts, such as breast enlargement, lumps, tenderness, pain or nipple discharge.

Telehealth use in Canada grew by more than 35% annually over the past 5 years Canada is a global leader in improving access to healthcare according to a new national study. “Across the country, use

of telehealth is growing rapidly, bridging the distance between patients and their care providers,” said Dr. Jennifer Zelmer, Senior Vice-President, Clinical Adoption and Innovation, Canada Health Infoway.

“Canadians do not have to travel as often to receive care, and the study reports improvements in access to care, quality, and productivity valued at millions of dollars last year.” Every province and territory in Canada is using Telehealth and almost 260,000 Telehealth sessions were held in 2010, supporting services such as remote care, education for health providers and administrative meetings.

Nearly half of the clinical Telehealth sessions delivered care to patients from rural and remote communities, which are home to 21% of Canadians. The report estimates that Canadians who received care via telehealth rather than travelling to other communities for care saved about $70 million in personal travel costs in 2010. In addition, there were benefits to the health system valued at $55 million per year (e.g., because of avoided federal or provincial subsidized travel costs or reduced hospitalizations for patients with chronic diseases).

ZRT Laboratory saliva testing included in at-home testing study from John Hopkins A recent study conducted by the Department of Gynecology and Obstetrics at John Hopkins Medical Institutions in Maryland, includes ZRT Laboratory saliva testing and ZRT internal research data in their examination of remote testing options. In the study, published in the May 2011 issue of Fertility and Sterility, investigators review and describe various over-the-counter testing products available to infertility patients. Doctors Brezina, Wallach, and Habel conclude that at-home testing represents an opportunity for physicians to involve patients actively in their care. “When properly used, these tests also may result in cost savings. Many of the technologies used are innovative and, with proper evaluation and implementation,

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INDUSTRY NEWS could serve as valuable adjuncts to medical practices,“ the study observes.

The article examines ZRT Laboratory salivary test kits, which measure a wide variety of hormones including estradiol, progesterone, testosterone, DHEA, and cortisol. The authors mention accuracy and the ease of use as the advantage of ZRT saliva testing. ZRT Laboratory, based in Beaverton, Oregon, is an industry leader for offering simple, at-home hormone and wellness test kits.

Near elimination of Varicella deaths in the US after implementation of the vaccination program Varicella has been preventable by vaccination in the United States since 1995. Previous studies reported a 66% decline in mortality rate during the first six years of the program. The analysis of US varicella mortality for 2002–2007 was updated and the impact of the first 12 years of the US varicella vaccination program on varicella deaths was assessed. During the 12 years of the mostly 1-dose US varicella vaccination program, the annual average mortality rate for varicella listed as the underlying cause declined 88%, from 0.41 per million population in 1990–1994 to 0.05 per million population in 2005–2007.

The decline occurred in all age groups, and there was an extremely high reduction among children and adolescents younger than 20 years (97%) and among subjects younger than 50 years overall (96%). In the last six years analyzed (2002–2007), a total of three deaths per age range were reported among children aged 1 to 4 and 5 to 9 years, compared with an annual average of 13 and 16 deaths, respectively, during the prevaccine years. The authors concluded that the impressive decline in varicella deaths can be directly attributed to successful implementation of the 1-dose vaccination program. With the current 2-dose program, there is potential that the most severe outcomes of a vaccinepreventable disease could be eliminated (Pediatrics. 2011 Aug;128(2):214-20.

PMID: 21788222).

The presence of aluminum has been detected in PPC brand Calcium Gluconate Injection 10% A recent notice from Health Canada and Pharmaceutical Partners of Canada Inc. (PPC) stated that PPC brand Calcium Gluconate Injection 10% has been found to contain aluminum. The Warning section of the package insert states: “This product contains aluminum that might be toxic. Aluminum might reach toxic levels with prolonged administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and because they require large amounts of calcium and phosphate solutions which contain aluminum. Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 µg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity.” To address the issue of aluminum toxicity, PPC is investigating alternate processes and alternate container materials, such as plastic vials, to determine if they will reduce the amount of aluminum present in the product and if they are suitable for utilization. PPC will inform healthcare professionals of the date at which the newly manufactured vials are expected to be available. Any cases of serious or unexpected adverse reactions in patients receiving Calcium Gluconate Injection 10% should be reported to PPI or Health Canada.

Hazardous flame retardants and chemical additives found in over half of 2011 child car seats The latest research on toxic chemicals in children’s car seats released by the nonprofit Ecology Center at www.HealthyStuff. org found that 60% of car seats tested contained at least one harmful chemical.

Over 150, 2011-model car seats were tested for bromine (associated with brominated flame retardants), chlorine (indicating the

presence of polyvinyl chloride, or PVC and plasticizers), lead, other heavy metals, and allergens. These substances have been linked to allergies, birth defects, impaired learning, liver toxicity, and cancer. Heat and UV-ray exposure in cars can accelerate the breakdown of these chemicals and possibly increase their toxicity. Babies are the most vulnerable population in terms of exposure, since their bodily systems are still developing and they spend many hours in their car seats. HealthyStuff.org provides comprehensive data on toxic chemicals in toys, cars, home improvement products and more, allows users to look up the bestand worst-scoring car seats with respect to toxic chemical content.

U.S. physicians spend nearly four times more than their Canadian counterparts on administrative costs A new University of Toronto study published in the August issue of Health Affairs, reports that U.S. physician practices spend almost four times as much money and 10 times as many hours on paperwork than Canadian practices. “The Canadian system is by no means perfect and often gets a lot of criticism, but there are points in time where we have to sit back and say our system does allow access for people and does provide quality care and it does deliver it in an efficient fashion compared to the U.S.,” said Dr. Dante Morra, lead author of the study. American practices spend $83,000 per doctor every year dealing with health insurers and other payers compared to Canadian practices that spend only $22,000. In addition, nurses and medical assistants in the U.S. spend 20.6 hours per week on administrative duties associated with payers and health insurers, whereas in Ontario, that work amounts to just 2.5 hours. Clinicians, physicians, and nurses are best suited to provide patient care but in the U.S., a significant amount of time spent is spent just dealing with paperwork associated with multiple different insurance companies. Despite the U.S.’s hefty spending, Morra said that Canada boasts better patient outcomes. ihpmagazine.com { October 2011 IHP | 39

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INDUSTRY NEWS

Study confirms accuracy of developmental screening tests that can be administered by family physicians BC Children’s Hospital and University of British Columbia (UBC) researchers have found that two existing screening tests are accurate in diagnosing development delays in children and could be incorporated in a busy family practice setting with relative ease. Parents can complete the Ages and Stages Questionnaire (ASQ ) or the Parents’ Evaluation of Developmental Status (PEDS) at home or in the family physician’s office, with the physician scoring the tests and providing results in a matter of minutes. “Only 30 per cent of children with developmental delays are identified prior to school age - whether that’s social, physical or learning - and most experts would agree that we should be identifying those delays earlier through regular screening,” says Dr. Marjolaine Limbos, principal investigator and a psychologist at BC Children’s Hospital.

However, researchers believe the tests are not routinely administered by Canadian family physicians because they have not been validated in a primary care setting and because of physicians’ concerns about having enough time to administer such tests in a busy practice. The authors of this research study, however, concluded that the ASQ and, to a lesser extent, the PEDS are accurate and can be administered effectively and at low cost.” (J Dev Behav Pediatr. 2011 Jul 14. PMID: 21760526)

Vitamin D and cancer campaign launched by the Vitamin D Council The Vitamin D Council, a nonprofit educational corporation based in California, launched their “Vitamin D and Cancer” campaign, presenting 20 detailed summaries of the evidence on the role of vitamin D in preventing cancer. The summaries can be found under the “Health conditions” tab on the Vitamin D Council website (http://www.vitamindcouncil.org/

health-conditions/cancer/). The Vitamin D Council hopes the campaign will spread more awareness about the importance of vitamin D sufficiency and the dangers of vitamin D deficiency. Some vitamin D and cancer facts that are presented in the summaries include: 1) many studies have found solar ultraviolet-B (UVB) and vitamin D associated with reduced risk of breast, colon, and rectal cancer; 2) randomized controlled trial with 1100 IU/ day vitamin D3 plus 1450 mg/day calcium found a 77% reduction in all-cancer incidence; 3) geographical studies have found reduced risk in mortality rates for 20 types of cancer in regions of higher solar UVB doses; 4) observational studies have found that the risk of breast, colon, and rectal cancer fall as vitamin D blood levels rise at least up to 40 ng/mL (100 nmol/L); 5) those who develop nonmelanoma skin cancer may have produced enough vitamin D to reduce their risk of internal cancers; 6) those with higher vitamin D blood levels at time of cancer diagnosis had nearly twice the survival rate of those with the lowest levels; and 7) higher UVB exposure early in life has been found associated with reduced risk of breast and prostate cancer.

MEG-3® brand Omega-3 EPA/DHA ingredients has announced the launch of Adult Essentials Gummies Omega-3 and Enhanced Multivitamin, both with Omega-3 EPA/DHA. These two new omega-3-containing adult gummies are part of Life Science Nutritionals’ new line of all natural gummy vitamins formulated for adults – the first of its kind in Canada.

Every 10 g serving (four gummies) of all natural Adult Essentials Omega-3 gummies provides 100mg omega-3 EPA/DHA, has no artificial sweeteners or colours, and contains nine essential vitamins. The enhanced multivitamin is the first to be enriched with fish oil and is approved by Health Canada. “While awareness about the importance of Omega-3 EPA/DHA at all life stages continues to grow, Canadians are still not consuming adequate amounts,” says Jon Getzinger, Chief Sales and Marketing Officer of ONC. “Incorporating EPA/ DHA into a multivitamin is a progressive step by Life Science Nutritionals, and we’re proud to be a part of this innovative product.” Adult Essentials Gummies are available at drugstores and supermarkets nation-wide.

An article in the Nutrition Business Journal stated that the year 2010 was another banner one for vitamin D, with supplement sales up another 30%. Vitamin D basked in the glow of promising research with more than 1000 studies looking at the vitamin’s effect on health conditions veering far beyond bone health to immunity, inflammation, and even protection against some forms of cancer.

Consumer awareness of Vitamin D’s importance was also on the rise, especially after TV’s Dr. Oz began touting its benefits and the importance of supplementation for adequate daily intake.

Laboratory test results of 60 multivitamins have shown that a supplement cannot be judged by its label or by its price. “Consumers should know that multivitamins vary widely in quality,” said Tod Cooperman, MD, president of ConsumerLab.com, White Plains, NY. “Fortunately, you don’t have to spend a lot to get a good multivitamin.”

ConsumerLab.com’s latest report on multivitamins sold in the U.S. and Canada (including three products for pets) found that the contents of the bottle do not always match the claims on the label. Eight multivitamins contained less of an ingredient than claimed, two contained more than claimed, one multivitamin intended for pets was contaminated with lead, tablets of another multivitamin failed to properly disintegrate, and three supplements listed ingredients in ways that did not comply with FDA requirements. Surprisingly, there was

Vitamin D sales increased in 2010

Life Science Nutritionals launches adult essentials gummies with EPA/DHA Ocean Nutrition Canada Limited (ONC), the provider and supplier of

Multivitamin quality varies widely

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INDUSTRY NEWS almost no connection between price and quality. Many inexpensive multivitamins (ranging in price from 3 to 14 cents per day) passed every test. At the same time, several relatively expensive products (some costing more than 50 cents or even more than $1 a day) failed ConsumerLab.com’s review.

This review is available online.

Metagenics partners with Vitamin Angels to help children with vitamin A deficiencies Metagenics, Inc. has announced that it will partner with Vitamin Angel’s Operation 20/20 outreach program to eliminate vitamin A deficiency among infants, children and pregnant mothers worldwide. For every two bottles of Metagenics’ omega-3 fish oil supplements that is sold, Metagenics will fund nutritional support for a child under five years of age for one year. “We are proud to partner with Vitamin Angels in an international program to reduce mortality and sickness in some of the most vulnerable and underserved populations in the world,” said Jeffrey Bland, Ph.D., FACN, FACB, the chief science officer for Metagenics, Inc. “Our mission at Metagenics is to help individuals achieve optimum health. Now, people can help a child in need to be healthy, while also improving their own health when purchasing two bottles of our omega-3 fish oil supplements.” “With Metagenics’ help, Vitamin Angels is now reaching over 24 million children in the U.S. and in 40 countries around the world,” said Howard B. Schiffer, president and founder of Vitamin Angels. “For the children and mothers we are serving, these vitamins are giving them a chance to lead full and productive lives.

We are honored to have Metagenics as a partner in this important effort.”

Chiropractors cautioned against insurance fraud The Toronto Star has reported that practitioners’ signatures and/or credentials are being utilized for insurance fraud without the professional’s knowledge. The article titled Shady clinics bill 1.3 billion in bogus car insurance claims scam, was

written by Michele Henry and published on July 13, 2011 in the Toronto Star. It states, “Insurance companies only pay out if treatment is given by a regulated health professional — a doctor, chiropractor, physiotherapist, or massage therapist. It appears that [bogus] clinics sometimes steal a professional’s information. In other cases, a professional briefly worked in the clinic and left behind a collegeissued registration number and electronic signature.” Henry also writes, “Health care professionals from all disciplines say the province must do something to stop their credentials from being misused.” Insurance investigators claim that more than 300 clinics in the Greater Toronto Area loosely connected in fraudulent rings are working this system.

The new Canada Consumer Product Safety Act introduces new cadmium guideline The Canadian government is taking action to protect children from dangerous products by proposing a new guideline regarding the amount of cadmium that may be found in children’s jewellery. Cadmium is a heavy metal known to be highly toxic when ingested. Health Canada is proposing a guideline regarding total cadmium concentration in children’s jewellery of 130 parts per million (0.013%). It is believed this concentration will help protect children from cadmium poisoning following accidental ingestion, or prolonged licking and sucking, of these products. “Parents want the products they buy for their children to be safe”, said Pamela Fuselli, Executive Director at Safe Kids Canada. “Young children explore their world through touch and taste, so guidelines like this ensure products children use often will be safer.” With the new Canada Consumer Product Safety Act, Canada will continue to monitor the marketplace and will take appropriate action when levels of cadmium in excess of the guideline are found in children’s jewellery. Health Canada may also seek the introduction of regulations limiting cadmium in children’s jewellery via the federal regulatory process.

Montreal will host the 22nd edition of the World Cancer Congress in 2012 The World Cancer Congress (WCC) has been held in many cities around the world since 1933. For the first time, it will take place in Canada in 2012 (August 27-30) at the Palais des Congrès in Montreal. Organized by the Union for International Cancer Control (UICC) in collaboration with the Canadian Local Host Committee (LHC) composed of the Fondation québécoise du cancer, McGill University, and Université de Montréal, the WCC is expected to attract more than 3000 participants and world leaders in the fight against cancer from 120 countries. The 2012 WCC will provide education and training opportunities throughout the program including interactive meetings, forums, workshops and sessions.The program consists of four tracks, each directly linked to one or more of the World Cancer Declaration targets: 1) prevention and early detection; 2) cancer care and survivorship; 3) palliation and pain control; and 4) systems in cancer control. The preliminary program along with online services (registration and hotel services) will be launched on November 4th, 2011 (www.worldcancercongress.org).

New Chapter announces acquisition of Canadian distribution rights New Chapter, Inc. has announced the acquisition of its Canadian distribution rights by its newly formed subsidiary, New Chapter Canada, Inc. New Chapter Canada acquired the distribution rights of New Chapter products from the Canadian company, Advantage Health Matters.

Beginning immediately, New Chapter Canada will introduce new bilingual packaging, brochures, national advertising, and a new bilingual Canadian website.

New Chapter Canada’s newly appointed General Manager, Disa Pratt, believes that “Gaining control of our distribution rights gives us the ability to have a more direct relationship with retailers. We can now more fully utilize our soul to soul marketing approach in better serving our customers.” • ihpmagazine.com { October 2011 IHP | 41

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Running out of steam?

You might be iron-deficient!

The body uses dietary iron to transport vital oxygen to all its tissues. However, many people, especially women, children, elderly people and athletes, do not get enough iron to satisfy their needs. Are you finding it difficult to get through the day?

More common than you might think …

Did you know that one woman in four is iron-deficient? Iron deficiency can make you feel faint, tired and irritable, and make it difficult to concentrate. Other signs that your body’s iron levels are too low include: dark circles under the eyes, headaches, pale skin and an increased need for sleep.

Lack of iron is the most common nutritional deficiency in the world. There are varying degrees of iron deficiency – and you may not even be aware that your iron is low. Elderly people, athletes, pregnant and nursing women, and vegetarians may have an increased need for iron supplementation.

Iron is essential

Since your body cannot produce iron by itself, you have to get it from your daily diet. Most of your iron goes to making hemoglobin – the colouring substance of red blood cells. Iron is essential for the transportation of oxygen in the body. It’s almost impossible to get enough iron from your daily diet to ensure the proper functioning of your body… Do you eat 15 cups of broccoli, 18 eggs or generous portions of liver and kidneys each week in order to get all the iron your body needs?

Probably not!

The natural solution!

Floradix, a plant-based liquid iron supplement, may help to improve your iron levels. Floradix is easily absorbed by the body, has no harmful effects on the digestive tract and offers positive results.

Made from highly soluble iron gluconate, as well as whole foods and co-factor vitamins, Floradix is highly absorbable and quickly replenishes iron levels, which helps to restore energy! Today, Floradix is highly recommended by health care professionals because it is clinically

proven to normalize low iron levels and is non-constipating as well.

Floradix users find that it reduces fatigue and stress; and many have also reported that it has improved their general quality of life. Trust Floradix, North America’s most recommended iron supplement! •

Low energy?

Are you iron-deficient?

Floradix® – your natural iron solution

[ ] Do you often feel listless, weak or irritable? [ ] Do you look pale, lack appetite or feel tired?

•

[ ] Are you often cold or chilly? [ ] Do you have brittle hair and nails? [ ] Are you pregnant or nursing or planning to become pregnant? [ ] Have you lost a lot of blood (e.g. from surgery, injury or donating blood)? [ ] Are you vegetarian?

The more questions you answered “yes” to, the higher your risk of being iron-deficient. Iron deficiency often goes undetected, so you may want to ask your doctor for a serum ferritin test, the most sensitive measurement of iron stores in your blood.

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Low dosage, prolonged iron supplementation could prevent an increase in the risk of cardiovascular disease and a reduction in the promotion of carcinogenic processes (Sullivan 1999). As a result, examining Floradix (physiological doses of iron embedded in a plantbased food matrix) may prove useful in achieving health outcomes with few risks and side-effects.

• Reduced absorption of copper, zinc and molybdenum caused by competitive inhibition.

• Increased free radical damage caused by iron overload;

Pharmacological doses of iron are associated with: • Reduced patient compliance due to free iron in the intestinal tract causing irritation of the intestinal mucosa;

Only one in five women have iron stores considered adequate for pregnancy (40 µg/L – 70 µg/L) (Millman 2003). Fifty-eight percent of pregnant women have been shown to have iron deficiency at time of delivery (Makrides 2003).

Approximately 40% of women of child bearing years are considered to have low iron status (ferritin 30 µg/L) (Millman 2003). More conservative estimates suggest that 9% - 11% of women of child bearing years are iron deficient, with iron deficiency anemia present in 2% - 5% of this population (Looker 1997).

Background

If Floradix can effectively increase serum ferritin, then it can be used for the treatment of“prevention of iron deficiency anemia”. In addition, Floradix could also be used where the treatment indication is lack of iron causing “performance weakness”.

(1) Hemoglobin (2) Erythrocytes (3) Mean Corpuscular Volume (4) Hematocrit

Complete Blood Count (CBC)

Table 1. Diagnostic / survey tools used over the course of 16 weeks.

A semi-quantitative recording of around 90% of the foods eaten in Germany.

One-hundred fifty-five questions classified by general condition, psychological/social factors and organ systems about the patient’s: (1) Disease symptoms (2) Complaints or problems

Condition Questionnaire (CQ)

Nutritional Questionnaire (NQ)

(1) Demographic data (2) Current diagnosis, (3) Existing secondary illnesses (4) Illnesses over the last four weeks (5) Side-effects (6) Current medication

Description

Doctor’s Survey Form (DSF)

Diagnostic Tool

At baseline, and at weeks 4, 8 and 16, all subjects underwent assessment of serum ferritin levels, as well as a complete blood count (CBC). Subjects also completed subjective questionnaires relating to diet recall, adverse effects, and symptoms of fatigue (see table 1).

The study was conducted in 2002 at the Heidelberg Women’s University Clinic, Outpatient Department of Natural Medicine.

For 16 weeks, the treatment group supplemented 10ml three times per day of Floradix (30ml of Floradix delivers 30mg of elemental iron as ferrous gluconate in solution).

Forty-one women, ages 18 to 65 (mean age 39, 95% still menstruating), with documented low ferritin levels and no pre-existing medical conditions were randomized to either a control group (given nutritional advice on how to increase iron-rich foods) or a group which received the same dietary advice plus supplemental Floradix.

The present study was designed to determine whether women with a proven iron deficiency can be effectively treated with Floradix.

Secondary objectives were to determine the side effects of taking Floradix.

Study Design

Introduction

K.H. Adzersen, A. Loewe-Mesch, K. Freivogel, I. Gerhard Department of Gynecology, Endocrinology, and Fertility Disorders, Heidelberg Women’s University Clinic

Examination of the effectiveness of Floradix (liquid) in women with a low ferritin level—a prospective, random, open intervention study

4 weeks

12.50

Nutrition Group

13.00

Start

14.00

18.00

12 weeks

13.50

20.00

Nutrition + Floradix Group

8 weeks

13.00

20.00

93773

Literature cited Looker, A.C., Dallman, P.R. Carroll, M.D., Gunter, E.W., and Johnson, C.L. 1997.Prevalence of iron deficiency in the United States. JAMA. 277(12):973-6.

Makrides, M., Crowther, C.A., Gibson, R.A., Gibson, R.S., Skeaff, C.M. 2003. Efficacy and tolerability of low-dose iron supplements during pregnancy: a randomized controlled trial. American Journal of Clinical Nutrition. 78(1):145-53.

Millman, N., Byg, K.E., Ovesen, L., Kirchoff, M., Jurgensen, K.S. 2003. Iron status in Danish women, 1984-1994: a cohort comparison of changes in iron stores and the prevalence of iron deficiency and iron overload. European Journal of Haematology. 71(1):51-61.

Sullivan, J.L. 1999. Iron therapy and cardiovascular disease. Kidney International Supplement. 69(S):135-7.

Floradix is effective for preventing iron deficiency and for treating low serum ferritin—with minimal side-effects and high compliance by patients.

Conclusion

Figure1. Comparison of median serum ferritin values in Floradix supplemented versus control subjects over the 16 week treatment period.

0.00

5.00

10.00

15.00

20.00

25.00

Patients were asked the question, “How do you feel overall?”, as part of the subjective assessment of the study. “Good” or “very good” responses were obtained from 70% of subjects in the Floradix group and from only 28% of subjects in the control group.

Adverse effect monitoring demonstrated that only 10% of the subjects reported any concern with the intervention, with mild gastrointestinal discomfort being the most common complaint.

Baseline red blood cell counts were within the normal range, and did not increase over the 16 week treatment period.

Significant increases in serum ferritin were evident after only four weeks of supplementation in the Floradix group—highlighting that the impact of the intervention occurs quickly.

Floradix demonstrated an ability to rapidly and significantly increase ferritin levels in this population. Over the 16 week study duration, the median ferritin values rose from 13.0 µg/L to 20.0 µg/L in Floradix treated subjects, with no change (median 12.5 µg/L – 13.5 µg/L throughout the 16 week intervention period) in the control group (see figure 1).

Results

Esther Konigsberg, MD

COVER STORY

Bringing integrative medicine into medical school

By Philip Rouchotas MSc, ND Photography by Rive Gauche Media

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COVER STORY

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COVER STORY

I

ntegrated Healthcare Practitioners set out with a mission of bridging the gap between conventionally trained and integrative healthcare providers. Dr Esther Konigsberg, MD is single- handedly delivering major advances towards that mission. With an undergraduate degree from McGill in Psychobiology completed in 1980, Esther went on to receive her medical training (school and residency in family medicine) from McMaster in 1985. By the early 1990s her interest in integrative medicine had peaked and she began expanding her tool bag by pursuing training in a variety of areas outside the domain of conventional medicine.

“I was always interested in a different approach”, describes Esther. “All we were learning about in medical school was disease... there wasn’t anything about health!” “Our role models weren’t very healthy people; they were sleep deprived, ate quickly and poorly, sacrificed time with family to be a good doctor”. She describes multiple seminars offered by Deepak Chopra as immensely influential in terms of her current day practice model, as well as a two- year fellowship program in integrative medicine from the University of Arizona. Today, Esther is responsible for establishing the Introduction to Complementary and Alternative Medicine curriculum at McMaster University School of Medicine, exposing all students of medicine to the discipline of integrative medicine during their final year of study.

Dr Konigsberg established the Introduction to Complementary and Alternative Medicine curriculum at McMaster in 2007. It includes a lecture outlining a wide array of integrative techniques, as well as having students visit with at least one private practitioner of integrative medicine (Chiropractic, Osteopathic, Naturopathic, Chinese Medicine and an energy therapy by a regulated health care practitioner. ) for a half day. Students are encouraged to experience a treatment from an integrative healthcare provider of their choice, and report back to classmates on the type of practitioner visited, the treatment they experienced, and their overall impression of the strategies employed by the practitioner. The success of the program among medical students at McMaster has resulted in an expansion of the program in October of this year. A half day “Introduction to Complementary and Alternative Medicine” is being offered to nurse practitioners, occupational therapists, physiotherapists, midwives, physician assistants, and others.

Esther has expanded this vision of education on integrative medicine for conventionally trained physicians by sitting on the steering committee of the Consortium of Academic Health Centres for Integrative Medicine. Four schools in Canada and 46 schools in the United States are members of the consortium, including institutions such as Harvard, Yale, Columbia, Stanford, and the Mayo clinic. The consortium meets twice per year, with a mandate of furthering education, research, and clinical practice of integrative medicine.

In order for an institution to become a member of the consortium, the institution must have the backing of the institution’s Dean. Thereafter, the institution must satisfy at least two of the following three criteria: provide education in integrative medicine, conduct research in integrative medicine, and have a clinic of integrative medicine.

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COVER STORY

The Lakeshore Clinic Team: Dr. Heather Norman D.C. – Chiropactor Dr. Kathryn Wheatley D.C. – Chiropactor Dr. Lisa Cadotte D.C. – Chiropactor Dr. Nathalie Taraban-Lagois D.C. – Chiropactor Dr. Candice Gibbs D.C. – Chiropactor Dr. Ashley Worobec D.C. – Chiropactor Dr. Mahfam Amini D.C. – Chiropactor Val Lundy R.M.T. – Massage Therapists Amy Allen R.M.T. – Massage Therapists Julie Haskell R.M.T. – Massage Therapists Nancy Morin R.M.T. – Massage Therapists Sarah Verkaik R.M.T. – Massage Therapists Michelle Gilmore R.M.T. – Massage Therapists Linda Johnson R.M.T. – Massage Therapists Joanne Eustace R.M.T. – Massage Therapists Biljana Vasilic R.M.T. – Massage Therapists

Jacki Higenbottam R.M.T. – Massage Therapists Wojciech Sikora R.M.T. – Massage Therapists Dr. Jordan Robertson N.D. – Naturopath Laurie Burrows R.H.N. – Holistic Nutritionist Kristina Graham R.H.N. – Holistic Nutritionist Dr. Esther Konigsberg M.D., CCFP – Integrative Medicine Cosultant Victoria Jacques – Front Desk Staff/Health Assistants Kate Holloway – Front Desk Staff/Health Assistants Kristina Graham – Front Desk Staff/Health Assistants Nancy Manigold – Front Desk Staff/Health Assistants Elyse Walker – Front Desk Staff/Health Assistants Kim Latimer – Front Desk Staff/Health Assistants Enza Trott – Front Desk Staff/Health Assistants Sarah Launslager – Front Desk Staff/Health Assistants Sandra Fascinato – Front Desk Staff/Health Assistants

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COVER STORY

“Esther has expanded this vision of education on integrative medicine for conventionally trained physicians by sitting on the steering committee of the Consortium of Academic Health Centres for Integrative Medicine.”

Dr Konigsberg has been practicing as an MD in Burlington for over two decades... As her interest in integrative medicine expanded, her style of practice evolved with her new training. Esther chose to abandon the traditional model of conventional practice, and has since joined forces with two established multidisciplinary clinics in the Greater Toronto Area. Splitting her practice time between the Lakeshore Clinic in Burlington and the Commerce Court Health Centre in downtown Toronto, Esther has surrounded herself with a large team of integrative practitioners representing a wide array of disciplines. Esther describes that this eclectic mix of like- minded practitioners creates the environment she feels most comfortable practicing in.

Esther’s style of practice exemplifies her views on health, wellness, and the role of a physician. She describes the immensely detailed health history taken with each patient, with questions concerning energy, sleep pattern, diet recall, the patient’s impression of their purpose and meaning in life, stresses, and takes time to listen to “the patient’s life story”. From this detailed intake an individualized health plan is created. The plan includes interventions from the area of mind/ body medicine, typically in the form of a meditation prescription. Prescription for physical activity is routine, as is a detailed nutritional program. Vitamin/ mineral/ nutraceutical supplementation as well as botanical medicines are routinely included. Bioidentical hormone therapy is also a routinely utilized treatment strategy. When asked what types of patients are arriving, we were not surprised to learn a very diverse range of patient concerns were benefiting from this eclectic style of practice; cancer survivors, individuals with an array of autoimmune disorders, mental health concerns such as anxiety and depression, and an inspiring subset of patients who have reached midlife and are actively seeking health and wellness, or “prevention”. Dr Konigsberg adds with frustration that “we spend billions of dollars on end of life care, and neglect spending on primary disease prevention.”

IHP is grateful to Dr Esther Konigsberg and the teams at the Commerce Court Health Centre and the Lakeshore Clinic for allowing us to showcase their work and facilities to you. The introduction of education in integrative medicine into curricula of conventional medicine is an exciting level of progress that we hope all institutions of medical training in Canada work their way towards. In theory, the present teachings on usage statistics and imposed experience with a practitioner of integrative medicine can be expanded, possibly to include an introduction in clinical application of integrative medical therapeutics? The number of conventionally trained physicians implementing various aspects of integrative medicine in clinical practice is growing at an exponential pace; we would like to see their interest encouraged. •

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COVER STORY

The Commerce Court Health Centre Team: Shannon Dales, DC Susan DeWolfe, DC Elizabeth Douglas, DC Esther Konigsberg, MD Morgan Winton, BSc, ND Kelly Murphy, RMT Jennifer Ingram, RMT Christy Fee, RMT Scott Allen, BSCPT – physiotherapist Tara McGee, M.S.W., R.S.W. – psychologist and social worker Orly Karin Wachter, MSc, RD – registered dietician Angela Sofroniou – office manager

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Amount Per Cap (mg)

Quantity Crude Equivalent (mg per ml)

Deep Immune Vegicaps (200 mg capsule, 5:1 extracts)

Products Professionals Prefer® Phone: 800.219.6226 | Fax: 888.219.6226

www.stfrancisherbfarm.com

Health Canada Site License 300242 For details, write #110 on Free Info Page, page 96.

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Product MonograPh Bio-Fen ® ® Deep Immune Combo ) (AGA) for male or female pattern baldness.

Bio-Fen Plus is an oral natural health product used in the treatment of (Astragalus hereditary androgenic alopecia Without treatment, AGA is progressive, and causes social distress in many affected men and women (Sinclair 1998). Bio-Fen Plus contains extracts ® Traditional Medicine (TCM) recognized theasvalue of tonics.

In this vein, St. Francis inhibitors Herb Farm celebrated of fenugreekChinese seeds, saw palmetto berrieshas andalways flax lignans, as well specific vitamins.

Eachtime-honoured ingredient is known to possess of ’sthe enzyme ® qi tonic— Deep Immune —promotes overallforhealth andsymptoms stimulates associated immunity.with hereditary AGA. 5α-reductase.

These inhibitors are responsible relieving One of the primary causes of hair loss is a high level of the male hormone dihydrotestosterone (DHT) within the hair follicle (Vierhapper, 2001).

For peopleare with AGA, their follicles have a greater number receptorssystem to which attaches.

5-α-reductase theother enzymatic Qi tonics valuable to anyone who wants greater energy,ofa androgen stronger immune andDHT increased resistance to the flu,catalyzes colds and conversion of testosterone to dihydrotestosterone, which binds to the receptor five-fold more avidly than the parent compound (Sinclair 1998). ® infections. The herbs in Deep Immune also restore normal adrenal function, improving stamina, overcoming fatigue and helping the body cope withpalmetto stress, overwork and chronic illness. This highly effective product is now available in vegicaps.

Vitamins Saw (Serenoa repens) In a Polish study of 46 women who had symptoms of diffuse alopecia, calcium Standardized (lipophillic) Serenoa extract has been found to be a potent inhibitor pantothenate orally twice adisorders. day in doses of 100 mg for of 5α-reductase, resulting in decreased tissue DHT. An open-label, dose response In TCM, the use of qi tonic herbs is of primary benefit in adjunctive cancer treatmentswas and for administered treating immune This method offour to five months, and vitamin B6 was injected every day for 20 to 30 days and repeated study was conducted on 42 healthy males to determine the effect of a combination therapy is called ‘Fu Zheng’ therapy, meaning ‘to support normality’. enhance white(Brzezińska-Wcisło blood cell production.

Inwas TCM, cancer that andvitamin its again after six months 2001). It determined of carotenoid astaxanthin and saw palmetto berry lipid extract on DHT andQi tonics B6 administered parenterally for a is fewthus weeks induces improvement in the hair related symptoms are thought to The be due pathological qi astwo wellgroups: as a general deficiency of qi. Treatment aimed at removing pathological testosterone levels (Angwafor 2008). mentowere divided into one group 800 qi and at received tonifying themg/day qi. of the combination supplement and the other condition in a subset of women and reduces hair loss. group received 2000 mg/day of the supplement for 14 days. ANOVA-RM showed significant within-group increases in serum total testeosterone and significant Medicinal Ingredients dose Per capsule decreases in serum DHT from baseline in both dose groups (P=0.05). There was no significant difference between dose groups with regard to the increase of Fenugreek (Trigonella foenum graecum) 260 mg testeosterone or the decrease ofof DHT; A meta-analysis thetherefore effectsboth thatdoses were effective (Angwafor seed extract 4:1 2008). astragalus-based products have on Saw palmetto berry extract containing 160 mg Another tested liposterolic of Serenoa repens (LSESr) and betathestudy immune functionextract of lung-cancer 45% free fatty acids sitosterol in the treatment of males (23-64 years of age) with mild to moderate AGA. patients undergoing chemotherapy Flax lignans, standardized to 20% Six of 10 (60%) subjects were rated as improved at the final visit, thus establishing 100 mg secoisolariciresinol diglucoside (SDG) was published in 2006.

Theagainst analysis the effectiveness of 5α-reductase inhibitors AGA (Prager 2002). Chronic inflammation of the hair follicle is considered to be a contributing factor for AGA. A concluded that astragalus-based herbal D-calcium pantothenate (Vitamin B5) 10.40 mg study by Chittur et al sought to determine whether blockade of inflammation using definitely improve immune LSESrformulas and two anti-inflammatory agents (carnitine and thioctic acid) could alter Niacinamide (Vitamin B3) 10.25 mg the expression of molecular markersthe of inflammation (Chittur 2009). It was found function and reduce side effects of Pyridoxine HCl (Vitamin B6) 2 mg that the combination suppressed lipopolysaccharide-activated gene expression of chemotherapy. finding chemokines associated with This pathways involvedvalidates in inflammation and apoptosis.

Riboflavin (Vitamin B2) 1.58 mg The study concluded that 5-alpha inhibitors in combination with the use of astragalus inreductase traditional blockade of inflammatory processes could represent a new two-pronged approach Folic acid 0.095 mg and helps explain the in the Chinese treatment ofmedicine AGA. Biotin 400 mcg beneficial effects of Deep Immune®.

Fenugreek Seeds non-Medicinal Ingredients Fenugreek seeds contain 5% to 30% protein, steroid saponins, sterols, flavonoids and alkaloids (notably trigonelline and choline). Steroid saponins bind and Inert microcrystalline cellulose and vegetable-based magnesium eliminate extra cholesterol and hormones in the body; DHT is made from stearate in a veggie-based capsule Modern clinical areisconfirming the age-oldTherefore, traditionswhen of TCM, testosterone, which studies is in turn made from cholesterol. excess specifically insofar as astragalus-based qi tonics improve outcomes in cholesterol is eliminated, less DHT can be made (Stark 1993).

In a study of 20 cancer. Ability to maintain/increase white blood cell counts during chemotherapy protocols has become the most common rationale for the Recommended adult dose: One capsule per day adults who consumed 12.5g and 18.0g of germinated fenugreek seed powder for application of astragalus-based therapies in complementary cancer management.

At the same time, however, it is perhaps more appropriate to one month, higher levels of consumption resulted in a significant reduction in total highlight and evidence of improved survival.

While the focus of the McCulloch review centers upon application in cancer management, astragaluscholesterol low-density lipoprotein (LDL) levels (Sowmya 1999).

based formulas have been researched in controlled settings for a wide array of indications: hay fever, asthma, hypothyroidism, kidney disease, and

Flax lignans systemic lupus erythematosus.

Flax reduces the amount of DHT produced by reducing cholesterol levels in the body. A meta-analysis of 28 studies between 1990 and 2008 showed that flaxseed significantly reduces circulating LDL-cholesterol concentrations (PanImmune® has garnered glowing reviews from naturopathic doctors Having proven effective overtotal moreand than 20 years of clinical use, Deep 2009). Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L nationwide. A New Brunswick naturopathic doctor points out that: “I have had a great deal of positive feedback from patients using Deep (95% CI: -0.20, 0.00 mmol/L) and 0.08 mmol/L (95% CI: -0.16, 0.00 mmol/L), Immune® Significant to help speed their recovery fromwith various conditions such as mononucleosis and following chemotherapy.” An Ontario respectively. reductions were observed wholedebilitating flaxseed (-0.21 and -0.16 mmol/L, respectively) and®-0.16 mmol/L,inrespectively) ND states further that, “Iand uselignan Deep(-0.28 Immune extensively my practice. I find it very useful for chronic allergies, autoimmune and chronic supplements (Pan 2009).

immune deficiency.”

Deep Immune is now available in both liquid form and as an encapsulated powder extract in a 5:1 ratio. Recommended daily dose for adults is References Angwafor F III, Anderson ML. An open label, dose response study to determine the effect of a dietary supplement on dihydrotestosterone, testosterone and estradiol levels in healthy males. J 2 ml four times daily for tincture, and 2 capsules twice daily for extract.

Int Soc (60 Sportsdrops), Nutr 2008;5:12. ®

Brzezińska-Wcisło L. Evaluation of vitamin B6 and calcium pantothenate effectiveness on hair growth from clinical and trichographic aspects for treatment of diffuse alopecia in women. Wiad Lek 2001;54:11-8. ®

All our products, including Deep Immune , are thoroughly tested for contaminants, including pesticide residues, heavy metals, and for microbial

Chittur S, Parr B, Marcovici G. Inhibition of inflammatory gene expression in keratinocytes using a composition containing carnitine, thioctic acid and saw palmetto extract. Evid Based content. Alternat Med 2009.

Complement Pan A, Yu D, Demark-Wahnefried W, Franco OH, Lin X. Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr 2009;90:288-97.

For more information, see Dr. Anthony Godfrey’s book, Deep Immunity. An audio CD of the same is also available at no charge, upon request. Both can

Prager N, Bickett K, French N, Marcovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic Altern Farm Complement Med 2002;8:143-52. be obtained from St. alopecia.

FrancisJHerb at: www.stfrancisherbfarm.com.

Serenoa repens monograph. Alternative Medicine Review 1998;3:227-9.

Sinclair R. Male pattern androgenetic alopecia. BMJ 1998;317:865-9.

Sowmya P, Rajyalakshmi P. Hypocholesterolemic effect of germinated fenugreek seeds in human subjects. Plant Foods Hum Nutr 1999;53:359-65.

Stark A, Madar Z. The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on bile acid absorption and cholesterol levels in rats, Br J Nutr 1993;69:277-87.

Vierpper H, Nowotny P, Maier H, Waldhausl W. Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/ dilution and mass spectrometry. J Clin Endocrinol Metab 2001;86:5762-4.

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CLINIC PROFILE

Dundas Naturopathic

Centre What every ND aspires to be

By Philip Rouchotas MSc, ND Photography by Dean Sanderson

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CLINIC PROFILE

T

he Dundas Naturopathic Centre is home to three of the most experienced NDs in the country. Founded by Dr Jim Spring, DC, ND originally as a chiropractic centre in 1981, Dr Spring went on to complete training as a naturopathic doctor and has practiced as such ever since. Dr Marilyn May, ND joined the clinic at about the same time Dr Spring completed his naturopathic training, and a few years later in 1990, Dr Paul Saunders, PhD, ND joined the team.

Six years ago I had the privilege of visiting Phoenix, Arizona, for an annual meeting of the American Association of Naturopathic Physicians. While at the conference, organizers had scheduled a bus trip to the Southwest College of Naturopathic Medicine (SCNM) in Phoenix, and I jumped at the opportunity to visit the campus. At that time, I had never seen a naturopathic college other than the Canadian College of Naturopathic Medicine (CCNM). Walking into the doors of SCNM was an experience difficult to describe; like a sense of being home... The familiar words of the naturopathic oath hanging from banners on the ceiling as you walk through the main corridor...

Pictures of herbal medicines, displays of tools of the naturopathic profession. Stepping through the doors of the Dundas Naturopathic Centre was much like that experience; a sense of coming home.

The Dundas Naturopathic Centre represents the pinnacle of eclectic delivery of integrative medicine. The dispensary serves as a seminar in the art of custom compounding; a base cream serves as a vehicle for individualized botanical topicals; oils added to the cream are made from Drâ&#x20AC;&#x2122;s Saunders and Mays personal garden; homeopathics are prepared by dropping liquid preparations into vials of naive pellets. Naturopathic doctors are trained in the use of approximately 400 herbs- seemingly the entire armament is on display in tincture form. Beyond herbal medicines and homeopathics, several hundred nutritional agents are made available, a range too broad to attempt to describe.

The facility itself is reflective of the physicians who tend to its patients; modest, humble... A simple reception area, four large and spacious treatment rooms, decorated with beautiful pieces of art, and more diplomas and certificates than an individual could try to count. The dispensary is located at the epicentre of the facility, an area that sees a lot of traffic. One gets a sense that this is where the three doctors meet as they dart in and out of patient visits to prepare the individualized prescription the present patient is to receive, discussing between them the formulation being compounded.

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CLINIC PROFILE

All three physicians embrace a style of practice that showcases the true art and science of naturopathic medicine; no tool comprising the scope of naturopathic practice is neglected. Each modality is called upon frequently with virtually every patient seen; spinal manipulation, bowen therapy, acupuncture, clinical nutrition, homeopathy, herbal medicine, counselling, meditation; any one patient can expect a prescription that represents the full range of healing techniques naturopathic doctors are trained to use.

IV therapies are also commonly employed; Meyer`s cocktails, IV vitamin C, and custom applications that one gets introduced to by enrolling in the parenteral therapy certification curriculum, taught by Dr Saunders. A very wide array of integrative diagnostic tests are also utilized by the team, including food allergy panels, comprehensive stool analysis, urinary hormone profi les, urinary organic acids testing, provocation challenge heavy metal assessment, and many conventional tests.

Given the over 30 year tenure of the facility, it is not surprising to learn a reputation of impeccable care accompanies all three physicians. As IHP arrived to photograph and meet with the team, a patient visiting the clinic from Buffalo was wrapping up an IV treatment. Patients frequent the facility from across Ontario and neighbouring communities in the United States.

Likewise the number of patients seen in a given week should not be surprising; Dr Spring averages upwards of 150 patient visits per week. Dr Saunders is available to patients three days per week, in order to make time for ongoing commitments of

teaching at CCNM and responsibilities associated with his role as President of NPLEX. He still averages 10-15 patient visits per day. Dr May has chosen to balance practice with caring for her home garden and pursuing her interests as an artist and pianist, seeing 20-30 patients per week.

Dr Spring and Dr May have worked behind the scenes on behalf of naturopathic medicine for many years. Dr Spring has worked for the Board of Directors of Drugless Therapy - Naturopathy (BDDTN) in the past 10 years, including eight years as president.

Since that time, he continues to consult with the BDDTH and Transitional Council with regard to new legislation. He has been on the Naturopathic Physicians Licensing Examinations (NPLEX) board for 20 years and has been the president of the North American Board of Naturopathic Examiners (NABNE) for the past five years. Dr May is a past instructor in Nutrition and Endocrinology at CCNM, she has served as a past vice chairman of the Board of Directors at CCNM and as a President during the CCNM transition and as a requisitionist during the CCNM transition. Dr Saunders has chosen a path that sees training of the next generation of naturopathic doctors consume as much or more of his time than his clinical practice. In addition to serving on more boards than can possibly be listed here and maintaining an active role as Professor at CCNM for an array of courses, Dr Saunders is pre- booked for the next two years for receiving student externs to train with him in his practice. CCNM Intern Ashley Chauvin, was in fact present at the facility, fulfi lling a once per week for four month externship.

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CLINIC PROFILE

From Left to Right: Dr. Jim Spring, Jan Rostron, Carol Troitto, Dr. Marilyn May, Dr. Paul Saunders

Visiting the facility is like walking into the home of a close knit family.

Jan Rostron has been acting as office manager since 1982. She describes in a heart warming manner what it has been like to see generations of families come through the facility – grandparents that first came for treatment as newlyweds and now their children and grandchildren subsequently coming for treatment through the years as well. Dr Spring describes with satisfaction how five individuals he treated as children and young adults have gone on to become naturopathic doctors. Carol Troitto has likewise been serving the clinic for decades; it was quite the site as we stood around trying to determine what Carol’s “title” was...

I think we agreed on purchaser and office assistant. Dr Spring’s wife, Gail, plays an instrumental role in the day-to-day management of the facility as she is responsible for all bookkeeping and accounting.

Dr Saunders took a bad tumble a year or so ago while out for a run...

On my way out Dr Saunders jumped into Dr Spring’s office for what has been an ongoing course of treatment to fi x his injured knee. Dr Spring performed a half dozen orthopaedic assessments in a handful of seconds, a series of tests that would have taken me a half hour to complete. Three or four adjustments later, the treatment was complete.

Some applied kinesiology was used along the way, I think to help determine which manipulations were performed.

“Visiting the facility is like

walking into the home of a close knit family. Jan Rostron has been acting as office manager since 1982. She describes in a heart warming manner what it has been like to see generations of families come through the facility”

My visit to the Dundas Naturopathic Clinic was an amazingly inspiring experience. I strongly encourage each and every ND across the country, and the globe, to take a drive to Dundas Ontario some time. Th ree world- class physicians are showcasing the pinnacle of naturopathic care. • ihpmagazine.com { October 2011 IHP | 59

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COMPANY PROFILE

St. Francis Herb Farm:

A Unique Marriage of Wisdom and Quality A Family Business That’s 100% Canadian Owned and Canadian Operated

By Angela MacNeil, MSc, ND

S

t. Francis Herb Farm® began as a cottage industry, founded by its present owners, Jeremy and Monique Rivett-Carnac.

Drawing on visionary resources of head and heart, the company has been serving the health needs of North Americans with superior products for almost a quarter of a century. In the early days, Jeremy and Monique learned the art of wildcrafting herbs in British Columbia and today, along with their three children and 27 employees, they operate a modern state-of-the-art facility and thriving herbal business in the Upper Ottawa Valley of Eastern Ontario.

In an increasingly hectic world, it is comforting to know that some things never change, especially good things. The staff at St. Francis Herb Farm® are strict believers in the principles and timeless truths of “herbal wisdom”. That is why they have dedicated themselves to

providing natural remedies made from the finest quality herbs— herbs carefully harvested and processed in accordance with the practices of sustainable agriculture and fair trade. The primary focus of the company is the wellbeing of individuals utilizing their products and this drives the quest for quality that underlies every aspect of the production process “from the ground up”—from growing and harvesting the herbs to formulation and packaging of the final product. Sourcing of suppliers has always been a paramount concern; it is a key part of the way the company views the whole concept of corporate responsibility. Central to the ethical and philosophical vision of the company is their encouragement of and support for local Canadian organic growers. In this way, St. Francis has successfully stimulated employment and empowered fellow members of their community in the vital arena of prosperity and economic growth.

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COMPANY PROFILE

“Quality—Conscientiously Achieved®” serves as the company motto as St. Francis Herb Farm® recognizes the importance of properly grown and harvested raw herbs as the foundation for a quality finished product. St. Francis’ commitment to quality goes hand-in-hand with their holistic approach to health, harking back to a more traditional view of health and balance in the human body. This crucial concept underlies the second company motto: “Rediscover the Wisdom®”. The company strives to recover and make available some of the perennially valid ways of healing that have been lost or forgotten, while taking into account the latest scientific research and medical findings.

Because St. Francis has always set such a high premium on the excellence and quality of their products, the company has established many of the basic standards for the herbal industry across Canada. In fact, St. Francis was the first Canadian company in the herbal industry to identify its products as being truly “organic” and was one of the first herbal companies to use exclusively certified organic, organically grown, and wildcrafted herbs.

Over the years St. Francis has developed more than 200 products, ranging from single tinctures and combinations to oils, salves, lotions, and creams. The uncompromising quality of each product has helped St. Francis Herb Farm® retain its key role on the industry’s cutting edge. Formulas such as Deep Immune®, EchinaSeal®, HepatoDR® (Milk Thistle Combo), and Laprinol (Cleavers Combo) have been in use for almost two decades. Tried and true, they have withstood the test of time and will certainly remain useful for many more years to come.

Although the company specialized in liquid herbal extracts during its early years, more recently St. Francis has been expanding into the area of encapsulated powdered extracts, in recognition of the contemporary world’s desire for more convenient dosage forms.

Modern-day, chronic “busy-ness” has brought with it a host of

immune conditions and St. Francis Herb Farm acknowledges this connection by focusing intensely on their immune products, particularly Deep Immune®, which is a superbly crafted combination of traditional Chinese herbs and adaptogens. St. Francis has also been establishing a greater market presence in sports medicine with various topical creams and salves. Of course, true to their roots, St. Francis is continuing to create liquid formulations and hopes to create new formulas in the coming years, as the company matures and management is transitioned to Jeremy and Monique’s eldest son, Paul.

St. Francis Herb Farm Inc. has been a registered GMP (Good Manufacturing Practice) manufacturer of quality herbal products since 2006. GMP is a process control quality system mandated

by Health Canada that ensures manufacturing processes, documentation, and training result in consistent quality for every product made. In addition, St. Francis is now engaged in obtaining HACCP certification for early 2012. HACCP is an acronym for “hazardous analysis critical control points” and is a systematic, preventative approach to food safety; it is also applicable in the herbal product and pharmaceutical industries. HACCP addresses physical, chemical, and biological hazards in an effort to prevent contamination. By continually improving quality initiatives through GMP and HACCP, St. Francis provides customers with not only high quality herbal products but also uncompromised safety.

St. Francis continues to work diligently with the Natural Health Products Directorate (NHPD), making every effort to mesh its already high standards with those proposed by the agencies of government in the dynamic and growing Canadian natural health products industry. Such measures will ensure that quality continues to be the benchmark by which St. Francis Herb Farm, their manufacturing procedures, and final products are known.

St. Francis continues to set the standard for herbal medicines across Canada - to your good health! • ihpmagazine.com { October 2011 IHP | 63

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FEATURE CHOLESTEROL

Does

cholesterol drive coronary

atherosclerosis?

A critical review of available evidence

By William R Ware, PhD

Introduction

Cholesterol and in particular low-density lipoprotein (LDL) has been called the driving force of atherosclerosis (Grundy 2008). But this widely held view is merely a hypothesis based almost entirely on studies with cardiac event endpoints rather than direct measurement of coronary plaque burden and progression. Extensive data continues to accumulate indicating that serum total cholesterol (TC) and LDL in asymptomatic individuals are not associated with either the extent or progression of coronary plaque, as quantified either by non-invasive electron beam tomography (EBT) or coronary computed tomography (CT) angiography (Ware 2009a). Non-invasive imaging can lead to reassignment of risk and prevent unnecessary concern or therapy (Church 2007). Eight studies involving over 27 000 asymptomatic patients found that those with a zero calcium score had an extremely low average annual coronary event rate (6.6 per 10,000), even though individuals with a zero calcium score still may have non-calcified plaque (Greenland 2008). The risk of adverse coronary events strongly increases with calcified plaque burden (Church 2007).

William R Ware, PhD Emeritus Professor, Faculty of Science University of Western Ontario 14 Metamora Cres.

London, Ontario, Canada N6G 1R3 warewr@rogers.com

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FEATURE CHOLESTEROL Some Inconvenient Questions

Those who believe in the above hypothesis must address the following inconvenient questions. ✢ Why have autopsy studies of the correlation between the extent of coronary atherosclerosis and serum cholesterol yielded null results (Ware 2008b)? The objection that the blood samples, mostly from accident or suicide victims, were obtained too long after death has been discredited (Mathur 1961). ✢ Why was it found (Hecht 2001b) that TC and LDL cholesterol did not correlate with either the extent or prematurity of coronary artery calcium (CAC) burden in 1105 consecutive, asymptomatic individuals self-referred for EBT? Why did these same researchers (Hecht 2001a) fail to find a correlation between LDL or TC and the CAC percentile (correlation coefficient 0.06 with a scatter plot showing no visible correlation) for 304 asymptomatic women? ✢ Why when 1653 men and women without a history of coronary heart disease (CHD) were subjected to coronary CT angiography using contrast media was there no correlation between total plaque burden (calcified, mixed and non-calcified) and total serum cholesterol with Spearman’s rho = -0.04 (Johnson 2009)? ✢ Why in a study of the impact of psychosocial factors on coronary calcification in 780 male and female asymptomatic individuals (n = 780), was there no correlation between TC or LDL and CAC score with Spearman correlation coefficients near zero? Multivariate analysis gave an odds ratio of 1.005 for LDL (Kop 2005). ✢ Why in the St. Francis Heart Study (Arad, 2005a) was no correlation found between LDL levels and CAC scores in 4903 asymptomatic individuals? ✢ Why for adults with familial hypercholesterolemia, were age-adjusted CAC scores not associated with cholesterol levels (Jensen 2000)? ✢ Why in a study (Kronmal 2007) of approximately 2900 individuals was the relative risk of incident CAC associated with LDL only 1.03 per 10 mg/dL and barely reached statistical significance (lower CI 1.01)? ✢ Why did a recent study of CAC scores and coronary risk find negligible correlation between LDL or TC and calcium scores in 1653 asymptomatic individuals judged free of CHD (Spearman’s coefficients = 0.07 and 0.08 respectively) (Sung 2008)? ✢ Why in a study of 177 asymptomatic patients of intermediate risk of CHD was a null result found (OR = 1.022, p = 0.361) for the odds of a positive association between CAC and LDL in a multivariate model (Ramadan 2008)? ✢ Why when 100 asymptomatic individuals underwent EBT were researchers (Takamiya 2004) unable to find any association whatsoever between LDL and CAC when using three multiple logistic regression models? ✢ Why did a study (Lee 2009) which found insulin resistance positively correlated with CAC progression in a community

based group of about 900 healthy adults fail to find in multivariate regression any connection with TC or LDL? ✢ Finally and perhaps the most important question, why is there no association between TC or LDL and the progression of CAC (Chironi 2002, Elkeles 2008, Gopal 2007, Hsia 2004, Kronmal 2007, Raggi 2005a, Sutton-Tyrrell 2001, Taylor 2008, Wong 2004, Yoon 2002)? All 10 studies cited involved EBT. The obvious answer to these questions is that the hypothesis is false. These questions directly address coronary plaque and thus do not involve arguments based on studies involving other vascular beds. The results are consistent over a wide range of age for both genders. It is also important that the correlation between carotid artery intima-media thickness and coronary atherosclerosis is modest, especially in asymptomatic individuals or those merely suspected of CHD, where correlation coefficients range mostly between 0.2 and 0.3 (Bots 2007). Results based on carotid intimamedia studies, a popular approach, should be extrapolated to coronary artery atherosclerosis only with great caution.

It might be argued that total plaque rather than calcified plaque should be the basis for judging the hypothesis, but in general, non-calcified plaque represents a very small fraction of the total plaque burden.

One study cited in the above questions (Johnson 2009) did indeed look at total plaque including non-calcified, calcified and mixed and found no correlation with TC. In addition, another study (Schmid 2008) found progression of non-calcified plaque volume in the left main and left anterior descending coronary arteries to be independent of whether patients had high or low LDL. Implications and Related Cholesterol Issues

LDL as a surrogate endpoint for CHD risk The above results do not support the widely held view that a diet high in saturated fat is atherogenic and increases the risk of CHD because it modestly raises LDL which in turn stimulates atherosclerosis. The role of saturated fat in CHD was already conclusively challenged two decades ago (Ravnskov 1998). Since then, three studies and a meta-analysis all reached the same negative conclusion (Hu 2010, Jakobsen, 2010, Siri-Tarino, 2010, Yamagishi, 2010). Also, increased saturated fat intake leads to a beneficial decrease in small dense LDL, and greater intake in saturated fat was found to reduce progression of coronary arthrosclerosis (Accurso 2008).

Determinants of plaque progression In the ten coronary plaque progression studies cited above, the prior existence of calcified plaque and hypertension were the most frequently found statistically significant positive risk factors, followed by diabetes, lipoprotein(a), triglycerides, smoking, the Framingham risk score, and high-density lipoprotein (HDL) (negative association), but these latter factors were not consistently identified. In terms of

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FEATURE CHOLESTEROL modifiable factors, the only strong association consistently found was hypertension. This association was also found in a study of individuals having a zero calcium score at baseline (Gopal 2007).

Insulin resistance also appears very important not only in progression but also in plaque burden (Koulaouzidis 2011, Lee 2009).

Plaques and lipid lowering The null results from the 22 trials cited above suggest that lowering LDL should have no impact on the prevalence or progression of coronary plaque and calls into question the proposed approach which targets LDL for asymptomatic persons of intermediate traditional risk of CHD who exhibit elevated coronary calcium (Naghavi 2007, Nasir 2006). Several randomized clinical trials employing statins and enrolling asymptomatic individuals support this inference. The placebo controlled studies found that statin therapy had no effect on the progression of coronary calcification as measured by the calcium score (Arad 2005b, Henein 2010, Houslay 2006). In trials comparing doses or different statins, atherosclerosis progression as measured by calcified plaque showed no relationship with on-treatment LDL levels and intensive therapy was unable to attenuate coronary artery calcium progression (Arad 2005b, Raggi 2005b, Schmermund 2006).

However, one study found statin therapy reduced plaque burden for non-calcified plaque but not CAC score or total plaque burden. Only 11% of the patients had non-calcified plaque (Burgstahler 2007).

Lipid-lowering trials in primary prevention The failure of statins to influence prevalence or progression of atherosclerosis prompts questions regarding statins for primary prevention. Michel de Lorgeril has discussed nine CHD-related negative cholesterol lowering trials done since the Vioxx affair of 2005 resulted in tightening of rules and regulations concerning conduct and reporting of trials (de Lorgeril 2009). This paper extends earlier related observations from de Lorgeril and colleagues (de Lorgeril 2008b, de Lorgeril 2006). These results challenge the cholesterol hypothesis as did the observation that half of a large serial cohort admitted to a hospital for heart attack had low or very low LDL (Al-Mallah 2009). In addition, a recent meta-analysis that recalculated primary prevention trial results after excluding all subjects with CHD found no impact on all-cause mortality (Ray 2010). Another recent meta-analysis of lipid lowering trials found the same result along with no reduction in serious adverse events in spite of a modest reduction in major CHD events (Wright 2010). It is interesting in view of the recent JUPITER lipid and CRP lowering trial (Ridker 2008), that three recent studies directly examined the correlation between the coronary calcium score and high-sensitivity CRP levels and found that there was no association (Elias-Smale 2007, Hosseinsabet 2008, Wong 2004). JUPITER has been criticized as flawed (de Lorgeril 2010). It may also have been confounded by the fact that rosuvastatin appears unique among statins in that it strongly elevates vitamin D levels and it is well known that low vitamin D status is a risk factor for CHD and also for coronary atherosclerosis (Ware 2010). Finally, when beneficial effects are observed, it is difficult to separate lipidlowering effects from pleiotropic effects.

Cholesterol as a risk factor for CHD This association is based mostly on studies of the risk of CHD events, and obviously not on directly observed coronary atherosclerosis. A recent review summarizes six disturbing facts (Ravnskov 2009) including the evidence that for women, men over 47, and in general the elderly, hypercholesteremia is a very weak risk factor for CHD, or in most cases, not a risk factor at all.

Studies of familial hypercholesteremia (FH) also fail to support the hypothesis if one considers that in young people, FH includes abnormalities in the coagulation system that constitute a strong CHD risk factor. In young men, the observed association may be confounded by the connection between cholesterol levels and stress-induced exaggerated blood pressure response (Ware 2008a).

The major studies frequently cited to support the hypothesis that cholesterol causes CHD (e.g. MRFIT, Framingham and MONICA) continue to come under attack (Rosch 2008).

Preventing, slowing or reversing plaque progression

Research mostly not involving cholesterol manipulation has started to address this issue. A recent study involved dietary advice and combined intensive lipid management (statin plus niacin) along with supplementation with omega-3 fatty acids and increased vitamin D status. The targets were triglycerides ≤ 60 mg/dL (0.68 mmol/L), HDL ≥60 mg/dL (1.55 mmol/L), and 25-hydroxy vitamin D levels ≥50 ng/mL (125 nmol/L). Out of 45 male and female subjects with calcium scores ≥50 Agatston units, after about 18 months, 20 subjects experienced a 15% drop in calcium score (maximum 64%), and 22 had their progression arrested or slowed to 12% whereas a 22% to 52% increase per year was expected (Davis 2009). In hypertensive patients, a calcium channel blocker was found to significantly slow the progression of coronary calcification when the control was a diuretic (Motro 2001).

Also, lowering the triglyceride/HDL ratio was associated with a beneficial impact on the progression of coronary atherosclerosis in diabetic patients treated with the drug pioglitazone (Nicholls 2011). In a mouse study, high HDL was found to promote rapid atherosclerosis regression and to alter the inflammatory properties of monocyte-derived plaque (Feig 2011). Emerging potentially modifiable risks factors associated with the severity or progression of coronary calcification include physiological stress (Seldenrijk 2011), depression (Janssen 2011), and sleep apnea (Kepez 2011).

Conclusion

Evidence has been presented indicating that atherosclerosis, which typically begins at a rather young age and progresses throughout life, is independent of total cholesterol or LDL levels, which calls into doubt classical etiological models and should encourage consideration of new theories (Ravnskov 2009). At some stage in this progression an acute cardiac event may occur which may or may not involve plaque rupture. Statins have some impact on the risk of acute events and have proved useful in secondary prevention but there remain numerous questions as to the importance of pleiotropic effects versus lipid lowering.

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FEATURE CHOLESTEROL However, the risk of sudden cardiac death is also independent of cholesterol levels, over 50% of all cardiac deaths are sudden and as discussed above, statins do not appear to influence mortality (de Lorgeril 2008a). Primary prevention drug trials remain highly controversial with criticism that has continued over several decades concerning issues such as age, gender, subject selection, cohort contamination by individuals with CHD, very low absolute benefits, high numbers needed to treat to prevent one adverse event, no impact on overall mortality, and the high prevalence of conflicts of interest (Wright 2010).

The literature cited and discussed above suggests that a new paradigm is needed, especially in the context of primary prevention of CHD, which deemphasizes (disregards?) TC, LDL, dietary cholesterol and saturated fat (de Lorgeril 2006, Ware 2008b). It seems clear that a new paradigm should instead emphasize significant lifestyle and dietary issues, inflammation, insulin resistance, triglyceride/HDL ratio, micronutrient and essential fatty acid status and psychological issues with plaque burden, progression, and regression as study or trial end-points (de Lorgeril 2008b, Mente 2009, Rosch 2008, Ware 2009b). •

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FEATURE CHOLESTEROL Kepez A, Niksarlioglu EY, Hazirolan T, Hayran M, Kocabas U, Demir AU, Aytemir K, Tokgozoglu L, Nazli N. Evaluation of association between obstructive sleep apnea and coronary risk scores predicted by tomographic coronary calcium scoring in asymptomatic patients. Anadolu Kardiyol Derg 2011.

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Scand Cardiovasc J 2008;42(4):244-249.

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25-30%5-α-reductase and increasescatalyzes HDL cholesterol For peopleSuper with AGA, their follicles have a greater number of androgen to which the enzymatic conversion of testosterone to dihydrotestosterone, whichacids binds(LCto the receptor five-fold more1997). avidly Through than the parent compound (Sinclair of the omega-3 long-chain polyunsaturated fatty 1-3% (Harris this mechanism, higher1998). doses

PUFAs) EPA and DHA in a 3:2 ratio. These fish derived LC-

Saw palmetto (Serenoa repens) PUFAs are(lipophillic) well known forextract their has anti-inflammatory effects, and Standardized Serenoa been found to be a potent inhibitor of 5α-reductase, resulting in decreased tissue DHT. An open-label, dose response have been the subject of extensive scientific research for their study was conducted on 42 healthy males to determine the effect of a combination impact on cardiovascular health, mood cognitive of carotenoid astaxanthin and saw palmetto berryand lipid extract onfunction, DHT and testosterone (Angwafor The men wereconditions divided intoincluding two groups: as well as levels a broad range 2008). of inflammatory one group received 800 mg/day of the combination supplement and the other arthritis, inflammatory diseasefor (IBD), liver disease group received 2000 mg/day ofbowel the supplement 14 days.and ANOVA-RM showed significant within-group increases in serum total testeosterone significant (Wall 2010). Arguably the most important of these and is the effect decreases in serum DHT from baseline in both dose groups (P=0.05). There of combined EPA + DHA on cardiovascular health. was no significant difference between dose groups with regard to the increase of testeosterone or the decrease of DHT; therefore both doses were effective (Angwafor 2008).

Fish oil has been demonstrated to reduce the risk of sudden coronary death, estimates to 45% reduced Another study testedwith liposterolic extractofofupSerenoa repens (LSESr)risk and betasitosterol the treatment malesrecently (23-64 years of age) with mild toattack moderate AGA. amonginpatients whoofhad survived a heart Six of 10 (60%) subjects were rated as improved at the final visit, thus establishing (Marchioli The Gissi Prevenzione trial(Prager conducted the effectiveness2002). of 5α-reductase inhibitors against AGA 2002). Chronic inflammation the hair follicle is considered be a contributing factor of for AGA. A in over 11 ofthousand patients foundtothat 850 mg daily study by Chittur et al sought to determine whether blockade of inflammation using EPA+DHA for two years reduced the riskandofthioctic sudden coronary LSESr and two anti-inflammatory agents (carnitine acid) could alter the expression of molecular markers risk of inflammation (Chittur It was found death by 45% and reduced of all cause death2009). by 25% that the combination suppressed lipopolysaccharide-activated gene expression of (Valagusaassociated 1999, Marchioli scientists chemokines with pathways2002). involved Other in inflammation andsuggest apoptosis.

The 5-alpha reductase in combination with thatstudy dosesconcluded as low asthat 250 mg per day ofinhibitors combined EPA+DHA blockade of inflammatory processes could represent a new two-pronged approach may be sufficient to obtain comparable outcomes (Mozaffarian in the treatment of AGA. 2006).

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of fish oil yield added benefits to cardiovascular health. EPA

Vitamins has also been to reduce thesymptoms inflammatory In a Polish study shown of 46 women who had of diffuseactivity alopecia, of calcium pantothenate was orally administered twice a day in doses of 100 mg for four to atherosclerotic plaques when incorporated into these arterial five months, and vitamin B6 was injected every day for 20 to 30 days and repeated lesions, slowing their progression 2010). again after thus six months (Brzezińska-Wcisło 2001). (Cawood It was determined that vitamin B6 administered parenterally for a few weeks induces improvement in the hair condition in a subset of women and reduces hair loss.

In addition to effects on cardiovascular health, supplementation with EPA+DHA has been shown to improve other Medicinal Ingredients dosemany Per capsule chronic inflammatory conditions, including liver damage Fenugreek (Trigonella foenum graecum) 260 mg inseed non-alcoholic extract 4:1 steatohepatitis (Tanaka 2008); clinical improvement of ulcerative colitis and improvement of Saw palmetto berry extract containing 160 mg joint andacids plasma markers of inflammation in patients 45% pain, free fatty with IBD (Aslan 1992, Brunborg 2008); and symptomatic Flax lignans, standardized to 20% 100 mg secoisolariciresinol diglucoside (SDG) improvements in autoimmune arthritis (Madland 2006) and osteoarthritis (Gruenwald 2009).

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Flax lignans Flax reduces the amount of DHT produced by reducing cholesterol levels in the body.

A meta-analysis of 28 studies between 1990 and 2008 showed that flaxseed References significantly reduces circulating andsupplementation LDL-cholesterol concentrations (Pan a double-blind, placebo-controlled, crossover study. Am J Gastroenterol. 1992 Apr;87(4):432-7.

Aslan A, Triadafilopoulos G. Fish oil total fatty acid in active ulcerative colitis: 2009). Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L Brunborg Madland TM, Lind and RA, 0.08 Arslanmmol/L G, Berstad A, Frøyland L. Effects of short-term oral administration of dietary marine oils in patients with inflammatory bowel disease and (95% CI: LA, -0.20, 0.00 mmol/L) (95% CI: -0.16, 0.00 mmol/L), joint pain: a pilot study comparing sealwere oil and cod liverwith oil. Clin Nutr.

2008 Aug;27(4):614-22. respectively.

Significant reductions observed whole flaxseed (-0.21 and -0.16 mmol/L, and lignan andJA,-0.16 respectively) Cawood AL, Dingrespectively) R, Napper FL, Young RH,(-0.28 Williams Ward mmol/L, MJ, Gudmundsen O, Vige R, Payne SP, Ye S, Shearman CP, Gallagher PJ, Grimble RF, Calder PC. Eicosapentaenoic supplements (Pan 2009). acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability. Atherosclerosis. 2010 Sep;212(1):252-9.

Gruenwald J, Petzold E, Busch R, Petzold HP, Graubaum HJ. Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis. Adv Ther. 2009 References Sep;26(9):858-71.

Angwafor F III, Anderson ML. An open label, dose response study to determine the effect of a dietary supplement on dihydrotestosterone, testosterone and estradiol levels in healthy males. J Int Soc Sports Nutr 2008;5:12.

Harris WS. n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997 May;65(5 Suppl):1645S-1654S. Brzezińska-Wcisło L. Evaluation of vitamin and calcium pantothenate on hair growth from clinical and aspectsafter for short-term treatment oforal diffuse alopecia in women.

Madland TM, Björkkjaer T, Brunborg LA,B6 Fröyland L, Berstad A, Bruneffectiveness JG. Subjective improvement in patients withtrichographic psoriatic arthritis treatment with seal oil. Wiad A Lek pilot2001;54:11-8. study with double blind comparison to soy oil. J Rheumatol. 2006 Feb;33(2):307-10.

Chittur S, Parr B, Marcovici G.E,Inhibition of inflammatory gene expressionEarly in keratinocytes using asudden composition carnitine, thioctic and sawmyocardial palmetto extract.

Evidtime-course Based Marchioli R, Barzi F, Bomba et al; GISSI-Prevenzione Investigators. protection against deathcontaining by n-3 polyunsaturated fattyacid acids after infarction: Complement Alternat Med 2009.

analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza

Pan A, Yu D, Demark-Wahnefried W, Franco OH, Lin X. Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr 2009;90:288-97.

nell’Infarto Miocardico (GISSI)-Prevenzione. Circulation. 2002 Apr 23;105(16):1897-903.

Prager N, Bickett K, French N, Marcovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the Mozaffarian D, Rimm EB. Fish intake, contaminants, human health: evaluating the risks and the benefits. JAMA. 2006 Oct 18;296(15):1885-99. treatment of androgenetic alopecia.

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Sowmya P, Rajyalakshmi P. Hypocholesterolemic effect of germinated fenugreek seeds in human subjects. Plant Foods Hum Nutr 1999;53:359-65.

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SECTION HEAD

Long-term

cannabis use

increased risk of psychosis?

Lorraine Stuyt ND Cognitive impairments that ensue with long-term cannabis use are well documented (Solowij 1995a, Solowij 1991, Solowij 2011a, Solowij 1995b, Solowij 2002) and evidence is emerging that suggests an influence in the development of psychosis and schizophrenia (Di Forti 2009, Leweke 1999, Thomas 1996, Tien 1990, van Os 2002). Though the risks of acquiring mental illness from long term daily or near-daily cannabis use remains a debate between the proponents of its legislation and its partisans of continued prohibition (Hall 1994), there is an emerging body of evidence that researchers implore not be ignored. Studies have surfaced that clarify the understanding of the effects of cannabis use on the brain and that have quantified the extent of the risks of long-term use (Leweke 2008, Murray 2007).

The Endocannabinoid System

Historically, explanation of reports of adverse effects associated with cannabis consumption, including psychotic episodes have been significantly hindered by a lack of knowledge regarding their underlying neurobiological and pharmacological processes (Leweke 2004). However, the discovery of the endogenous cannabinoid system in the late 1980s has assisted in elucidating the molecular basis of cannabis, the action of cannabis and cannabinoids in the brain, and the relationship these cannabinoids have with psychotic symptoms and disorders (Leweke 2004).

Lorraine Stuyt BSc, ND Volunteer Research Assistant Regional Mental Health Care - London St. Josephâ&#x20AC;&#x2122;s Health Care 850 Highbury Ave N, London ON, N6A 4H1 lstuyt@hotmail.com ihpmagazine.com { October 2011 IHP | 71

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FEATURE CANNABIS AND PSYCHOSIS The cannabinoid-1 (CB1) receptor has been discovered as the target for delta-9-tetrahydrocannabinol (Delta-9-THC) in the rat brain (Devane 1988). Delta-9-THC was the fi rst exogenous cannabinoid CB1 activator that was isolated from preparations of the cannabis sativa plant. Subsequently, two endogenous ligands for this receptor were identified: anandamide and 2-arachidonylglycerol (2-AG). In recent years, many studies have investigated the CB1 receptor and the endogenous cannabinoid system (Elphick 2001, Fernandez 1997, Giuff rida 2000, Howlett 1995, Manzanares 1999, Schlicker 2001, Wilson 2002). Studies on various mammals have found that the anatomical distribution of the CB1 receptor is highly consistent among different species (Herkenham 1990, Herkenham 1991, Matsuda 1993), concentrating in parts of the limbic system (particularly the hippocampus and the amygdala) and in the cerebellum (Solowij 2011b).

On a functional level, CB1 receptors are activated by endogenous cannabinoids such as anandamide and 2-AG at the presynaptic nerve terminal. Binding of these cannabinoids leads to a decrease in membrane permeability to calcium and potassium ions, as well as to a decrease in the activity of adenylate cyclase, thereby inhibiting the release of glutamate, dopamine, acetylcholine, and noradrenaline (norepinephrine) (Leweke 2004). GABA reuptake is also inhibited (Leweke 2004).

A role for the Endocannabinoid System in Psychosis and Schizophrenia

Since the discovery of the endocannabinoid system, a growing body of psychiatric research has focused on the role of this system in major psychiatric disorders (Leweke 2004). Evidence suggests that cannabinoid receptors, the pharmacological target of cannabis-derived drugs, and their accompanying system of endogenous activators may be dysfunctional in schizophrenia (Leweke 1999). Leweke et al purified and quantified endogenous cannabinoids from cerebrospinal fluid (CSF) of 10 patients with schizophrenia and 11 non-schizophrenic controls. It was found that CSF concentrations of two endogenous cannabinoids (anandamide and palmitylethanolamide) were significantly higher in schizophrenic patients than in non-schizophrenic controls (Leweke 1999). These elevated endogenous cannabinoids in schizophrenic patients are thought to reflect an imbalance in the endogenous cannabinoid signalling, which may contribute to the pathogenesis of schizophrenia (Leweke 1999).

Koethe (2009) explored the proposed homeostatic role of anandamide in schizophrenia. Their study included subjects not yet diagnosed with schizophrenia, but exhibiting signs of psychosis. CSF anandamide levels were assessed in subjects in this prodromal state of psychosis and in healthy volunteers.

Results revealed that anandamide levels in subjects in the prodromal state were significantly elevated and that those with lower levels of anandamide actually showed a higher risk for transiting to psychosis earlier. Th is anandamidergic up-regulation

in the initial prodromal course may suggest a protective role of the endocannabinoid system in early schizophrenia (Koethe 2009), reflecting a compensatory adaptation to the disease state (Giuff rida 2004). That CSF anandamide levels correlate inversely with psychotic symptoms suggests that anandamide release into the central nervous system may serve as an adaptive mechanism countering neurotransmitter abnormalities in acute psychosis (Leweke 2007).

Guiff rida and colleagues researched the influence that pharmaceutical treatment had on anandamide levels in patients with schizophrenia compared to anti-psychotic naïve individuals suffering a fi rst-episode psychosis to further understand the relationship between the endocannabinoid system, neurotransmission and psychosis. They found that individuals with schizophrenia treated with ‘typical antipsychotics’ (antagonists of the dopamine D2-like receptor) did not have the same elevations in anandamide levels, though individuals with schizophrenia treated with ‘atypical’ antipsychotics (antagonists of 5HT(2A) receptors) did (Giuff rida 2004). These findings are congruent with the hypotheses concerning the interactions between cannabis, endocannabinoids, and dopamine whereby cannabisinduced dopamine dysregulation may give rise to delusions and hallucinations (Kuepper 2010). Kuepper (2010) provide a review of possible dopamine pathways in psychosis based on animal research that suggests that delta-9-THC increases dopamine levels in several regions of the brain; however, such discussion, in its complexity, goes beyond the scope of this article.

The Relationship Between Cannabis Use, Psychosis and Schizophrenia

The consensus in the literature regarding the association between psychosis, schizophrenia, and cannabis use is one that is congruent with the vulnerability/stress model of schizophrenia developed by Nuechterlein and Dawson (Nuechterlein 1984). That is, cannabis is considered one stress factor among others that may either enhance or trigger schizophrenic symptoms (Leweke 2004). A community survey on the early course and onset of schizophrenia in Germany was able to differentiate three approximately equal sized groups of patients with cannabis-associated psychosis: patients who had been using cannabis for several years before the fi rst (prodromal) signs of schizophrenia emerged, patients who had experienced the onset of both cannabis use and schizophrenia within one month of each other, and patients who had started

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FEATURE CANNABIS AND PSYCHOSIS to use cannabis after the onset of symptoms of schizophrenia (Hambrecht 2000). According to Lousia Degenhardt & Wayne Hall (2002) “it is unlikely that cannabis use causes psychosis among persons who would otherwise not have developed the disorder. The evidence is more consistent with the hypotheses that cannabis use may precipitate psychosis among vulnerable individuals, increase the risk of relapse among those who have already developed the disorder, and may be more likely to lead to dependence in persons with schizophrenia”. Additionally, Degenhardt, Hall and Lyndskey (2003) state that “cannabis use does not appear to be causally related to the incidence of schizophrenia, but its use may precipitate disorders in persons who are vulnerable to developing psychosis and worsen the course of the disorder among those who have already developed it”.

Difference between delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD): Regional Brain Function and

validating their dissimilar consequences on regional brain function (Fuser-Poli 2009). CBD attenuated the neurofunctional engagement of the amygdala and cingulated cortex and reduced the electrodermal response when subjects viewed intensely fearful stimuli, verifying its anxiolytic effects. Alternatively, delta-9-THC modulated activation in frontal and parietal areas and augmented the electrodermal response; effects validating an increase in anxiety (Fusar-Poli 2009).

These differences in the behavioural effects of delta-9-THC and CBD are paralleled by differences in their mechanisms of action at the molecular level (Fusar-Poli 2009). Delta-9-THC binds to neuronal CB1 receptors (Devane 1992), which are found on GABAergic and glutamatergic neurons throughout the brain (Braida 2007, Herkenham 1990, Mechoulam 2003). CBD has a very low affinity for the cannabinoid CB1 receptor (Petitet 1998).

Neurophysiology

Brain Abnormalities and Long-term Heavy Cannabis Use

Data on the underlying composition of the herbal preparations (ie. the different natural cannabinoids present) or on the plasma levels of delta-9-THC, are generally not provided in retrospective clinical studies (Leweke 2004). Generally, the term ‘cannabis’ in the literature refers to all herbal cannabis preparations with a poorly defined mixture of different natural cannabioids. Only when a concentration is given or when a precise term is used can it be certain that the effects of a specific cannabinoid are being studied (Leweke 2004). It is important to note that delta-9-THC and cannabidiol (CBD), the two most common exogenous cannabinoids, have distinct symptomatic and behavioural effects (Bhattacharyya 2010). Where delta-9-THC impairs reaction on movement and response-inhibition tasks, causes acute psychotic symptoms, and destabilizes brain function, CBD does not impair performance or induce psychosis, appears to reduce anxiety, and stabilizes brain function (Fusar-Poli 2009).

There exists confl icting evidence concerning structural consequences of long- term cannabis use on the brain. A series of preclinical investigations demonstrated induction of neurotoxic changes in the hippocampus (Chan 1998, Landfield 1988, Lawston 2000, Scallet 1987) leading to further investigation in human trials. Yucel et al conducted a region-of-interest-based analysis using high resolution 3 Telsa magnetic resonance imaging (3-T MRI) to assess volumetric changes in the hippocampus and the amygdala (Yucel 2008). Subjects who were non-using healthy male volunteers and those with a long history of cannabis use were carefully screened for polysubstance abuse and mental disorders as well as for subthreshold psychotic symptoms and verbal learning abilities. Findings in this study corroborate with the above cited animal research suggesting that long-term heavy cannabis use is associated with significant and localized hippocampal volume reductions that relate to increasing cumulative cannabis exposure (Yucel 2008). Bilateral reduction in amygdala volume was also seen (Yucel 2008). Long-term heavy cannabis use and its association with smaller cerebellar white-matter volume similar to that observed in schizophrenia has also been shown (Solowij 2011b). Reduced volumes were more pronounced in patients with schizophrenia who use cannabis, but were apparent in healthy individuals with a cannabis use history as well (Solowij 2011b).

These findings indicate that heavy cannabis use across protracted periods exert harmful effects on brain tissue, and subsequently on mental health (Yucel 2008).

Functional magnetic resonance imaging (fMRI) was used in healthy volunteers to examine whether delta-9-THC and CBD had opposite effects on regional brain function in healthy volunteers with minimal cannabis exposure (Bhattacharyya 2010). Subjects were scanned on three occasions following oral administration of delta-9-THC, CBD or placebo while performing a verbal memory task, a response inhibition task, a sensory processing task, and when viewing fearful faces. Results revealed that delta-9-THC and CBD have opposite effects on activation relative to placebo (1) in the striatum during verbal recall, (2) in the hippocampus during the response inhibition task, (3) in the amygdala when subjects viewed fearful faces, (4) in the superior temporal cortex when subjects listened to speech, and (5) in the occipital cortex during visual processing (Bhattacharyya 2010). Using an eventrelated paradigm with faces that implicitly elicited different levels of anxiety, Fuser-Poli et al demonstrated distinct effects of delta-9-THC and CBD on neural activation with fMRI and electrodermal response during emotional processing further

Vulnerability and Genetics

Compatible with the vulnerability/stress model of schizophrenia, gene-environment interactions involving the catechol-Omethyltransferase Valine(158)Methionine polymorphism (COMT(Val158Met)) have been implicated in the causation of psychosis (van Winkel 2008). In a stress exposure study in members of the Greek army, carriers of the COMT Val158Met allele were more susceptible to the effects of stress on the psychosis ihpmagazine.com { October 2011 IHP | 73

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Feature cannabis and psychosis outcome than those with the catechol-O-methyltransferase Methionine(158)Methionine genotype (Stefanis 2007). In addition, carriers of the COMT Val(158)Met allele were more likely to exhibit psychotic symptoms and to develop schizophreniform disorder if they used cannabis; whereas cannabis use had no such adverse influence on individuals with two copies of the methionine allele (COMT(Met158Met)) (Caspi 2005).

schizophrenia. This increased risk was specific to cannabis use as opposed to the use of other drugs (Arseneault 2002). Two large studies, one out of Greece in 2004 (n=3500) (Stefanis 2004) and another out of the Netherlands in 2005 (n=2437) (Henquet 2005) found results adding credence to the hypothesis that cannabis use early in adolescents contributes to the risk of developing psychosis, particularly in those with a predisposition.

Cannabis use in adolescents is another gene-environment factor that increases the likelihood of experiencing symptoms of schizophrenia in adulthood (Arseneault 2002). After controlling for pre-existing psychotic symptoms, it was found in the Dunedin Multidisciplinary Health and Development study from New Zealand that cannabis use increased the risk of developing symptoms of schizophrenia in this cohort (Arseneault 2002).

One-tenth of those in this sample who were using cannabis by the age of 15 years had developed a schizophrenia-like disorder by the age of 26 years. Onset of cannabis use prior to the age of 15 years conferred the greatest risk of subsequently developing

Conclusion

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Manzanares, J., Corchero, J., Romero, J., Fernandez-Ruiz, J. J., Ramos, J. A., Fuentes, J. A. Pharmacological and biochemical interactions between opioids and cannabinoids. Trends in pharmacological sciences. 1999. 20(7): 287-294.

Stefanis, N. C., Delespaul, P., Henquet, C., Bakoula, C., Stefanis, C. N., Van Os, J. Early adolescent cannabis exposure and positive and negative dimensions of psychosis. Addiction. 2004; 99(10): 1333-1341.

Matsuda, L. A., Bonner, T. I., Lolait, S. J. Localization of cannabinoid receptor mRNA in rat brain. The Journal of comparative neurology. 1993; 327(4): 535-550.

Stefanis, N. C., Henquet, C., Avramopoulos, D., Smyrnis, N., Evdokimidis, I., MyinGermeys, I., Van Os, J. COMT Val158Met moderation of stress-induced psychosis.

Psychological medicine. 2007; 37(11): 1651-1656.

Mechoulam, R., Hanus, L. Cannabidiol: an overview of some chemical and pharmacological aspects. Part I: chemical aspects. Chemistry and physics of lipids.

2002; 121(1-2): 35-43.

Stella, N., Schweitzer, P., Piomelli, D. A second endogenous cannabinoid that modulates long-term potentiation. Nature. 1997; 388(6644): 773-778.

Mechoulam, R., Lichtman, A.H. Neuroscience. Stout guards of the central nervous system. Science. 2003; 302(5642): 65-67.

Thomas, H. A community survey of adverse effects of cannabis use. Drug and alcohol dependence. 1996; 42(3): 201-207.

Moreira, F. A., Aguiar, D.C. Anxiolytic-like effect of cannabidiol in the rat Vogel conflict test. Progress in neuro-psychopharmacology & biological psychiatry. 2006; 30(8): 1466-1471.

Tien, A. Y., Anthony J.C. Epidemiological analysis of alcohol and drug use as risk factors for psychotic experiences. The Journal of nervous and mental disease. 1990; 178(8): 473-480.

Morgan, C. J., Curran H.V. Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis. The British journal of psychiatry : the journal of mental science. 2008; 192(4): 306-307.

van Winkel, R., Henquet, C., Rosa, A., Papiol, S., Fananas, L., De Hert, M., Myin-Germeys, I. Evidence that the COMT(Val158Met) polymorphism moderates sensitivity to stress in psychosis: an experience-sampling study.

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2008; 147B(1): 10-17.

Morgan, C. J., Schafer, G. Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study: naturalistic study [corrected]. The British journal of psychiatry : the journal of mental science. 2010; 197(4): 285-290.

Munro, S., Thomas, K.L. Molecular characterization of a peripheral receptor for cannabinoids. Nature. 1993; 365(6441): 61-65.

Murray, R. M., Morrison, P. D., Henquet, C., Di Forti, M. Cannabis, the mind and society: the hash realities. Nature reviews. Neuroscience. 2007; 8(11): 885-895.

Wilson, R. I., Nicoll R.A. Endocannabinoid signaling in the brain. Science. 2002; 296(5568): 678-682.

Yucel, M., Solowij, N., Respondek, C., Whittle, S., Fornito, A., Pantelis, C., Lubman, D. I. Regional brain abnormalities associated with long-term heavy cannabis use.

Archives of general psychiatry. 2008; 65(6): 694-701.

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FEATURE Meditation and ADHD

Meditation,

Attention, and

Neuroplasticity Implications for the integrative care of attention- deficit/ hyperactivity disorder

By Elizabeth J Cherevaty, ND

A

ttention-deficit/hyperactivity disorder (ADHD) is the most common psychiatric disorder of childhood, affecting 3% to 10% of children (APA 1994, Sinha 2005, Szymanski 2001, Zylowska 2009) and may persist into adulthood (APA 1994). As defined by the DSM-IV-TR (APA 2000), essential features of ADHD include persistent inattention, hyperactivity and/or impulsivity; onset prior to age seven years; and the presence of symptoms in at least two settings, such as at school and home. Individuals with ADHD may experience difficulties in withholding attention from distractions, decisionmaking, regulating emotions, completing tasks or coping with a change in the requirements of a task (Baijal 2008, Sinha 2005).

They are at increased risk of developing significant adverse social, academic and emotional consequences (APA 1994, Kuhlmann 2010, Sinha 2005, Szymanski 2001). While pharmacotherapy is the cornerstone of conventional ADHD care (Kuhlmann 2010, Szymanski 2001), it effectively reduces symptoms in only 70% of patients (Sinha 2005, Szymanksi 2001), may provide no functional improvement, and may cause undesirable side effects (Jensen 2004). A multimodal treatment approach including a behavioural component is generally recommended to optimize treatment success (Baijal 2008, Kuhlmann 2010, Sinha 2005).

However, behaviour is rarely completely normalized even when pharmacotherapy and behavioural therapies are used in combination (Jensen 2004). Increasingly, families of children with ADHD are seeking suitable complementary and alternative

care options (Chan 2003, Sinha 2005). Meditation and yoga are modalities of complementary medicine (Wahbeh 2008) for which preliminary clinical and neurobiological evidence suggests a potential therapeutic benefit in the management of pediatric and adult ADHD. Meditation

Meditation is the ancient cognitive-spiritual practice of “stilling the fluctuations of the mind” (Baerentsen 2010). It consists of attentional self-regulatory techniques that are intended to cultivate physiological and psychological well-being (Lutz 2008, Raffone 2010, Slatger 2007, Wahbeh 2008). The various methods of meditation aim to attain deliberate, attentional self-regulation: a stable, attentive form of consciousness that differs from both ordinary wake- and sleep-states (Baerentsen 2010, Manna 2010). Two classifications of meditation are generally accepted: “focused attention” (FA) meditation and “open monitoring” (OM) meditation (Baerentsen 2010, Manna 2010). FA or “concentrative meditation” involves monitoring the focus of attention, detecting distraction, disengaging from the distraction and redirecting attention to the intended object (Manna 2010). These functions are linked with brain systems involved in conflict monitoring, selective and sustained attention (Manna 2010). OM or “mindfulness meditation” cultivates non-evaluative, non-reactive awareness of internal and external stimuli and appears to be related to brain regions involved in vigilance (Manna 2010). ihpmagazine.com { October 2011 IHP | 79

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FEATURE Meditation and ADHD Table 1: Neuroplastic effects of short- and long-term meditation practice: survey of studies Authors

Participants

Meditation Practice

Outcomes

Luders 2011, U.S.A.

(n=54): 27 active meditation practitioners , 27 healthy controls matched for sex, age, education and handedness

Mean practice experience: 23.3 +/- 12.2 yrs (Vipassana, Shamatha, Zazen and/or other styles)

Significantly greater white matter integrity in fiber tracts throughout the brain in meditators compared to controls

Tang 2010, China

(n=45) healthy undergraduates randomly assigned to integrative body-mind training (IBMT) (n=22) or relaxation group (n=23)

30 minutes of IBMT (mindfulness, mental imagery and relaxation training to achieve meditative state) or relaxation training 5 days per week for 1 month (total of 11 h of training)

Significantly greater white matter integrity in anterior cingulate cortex (implicated in self-regulation) after 11 h IBMT but not in relaxation group

Vestergaard-Poulsen 2009, Denmark

(n=20): 10 experienced Dzogchen meditators, 10 nonmeditator controls matched for age and handedness

Average practice experience: 2.2 h daily over 14-31 years (open awareness meditation in Tibetan Buddhism tradition)

Increased grey matter density in medulla oblongata, anterior cerebellum, and left superior frontal gyrus in meditators compared to controls

Holzel 2008 (as reviewed

by Chiesa 2010), Germany

(n=40): 20 long-term Vipassana meditators, 20 nonmeditator controls matched for sex, age, education and handedness

Mean practice experience: 2 h daily for 8.6 yrs

Increased grey matter concentration in the right anterior insula, left inferior temporal gyrus and right hippocampus in meditators compared to controls

Holzel 2007 (as reviewed by Chiesa 2010), Germany

(n=30): 15 long-term Vipassana meditators, 15 nonmeditator controls matched for sex, age, education and handedness

Mean practice experience: 2 h daily for 7.9 yrs

Stronger bilateral activations in the rostral anterior cingulated cortex and dorsal medial prefrontal cortex of meditators than controls

Lazar 2005 (as reviewed

by Chiesa 2010), U.S.A.

(n=35): 20 long-term Vipassana meditators, 15 matched nonmeditator controls

Mean practice experience: 6.2 +/4.0 h per week, for 9.1 +/-7.1 yrs

Brain regions associated with attention and sensory processing, including the prefrontal cortex and right anterior insula were thicker in meditators than controls

Neuroplastic Effects of Meditation on the Human Brain

Numerous neuroimaging studies using methods such as EEG (electroencephalography), PET (positron emission tomography), fMRI (functional magnetic resonance imaging), SPECT (singlephoton emission computed tomography) and DTI (diffusion tensor imaging) have been published reporting the functional and anatomical changes that occur in the brain, including attentionrelated structures, with meditation practice (Baerentsen 2010, Baigal 2008, Cheisa 2010, Luders 2011, Lutz 2009, VestergaardPoulsen 2009). During meditation, attentional and sensory processing regions of the brain become activated, and these regions have been found to be generally more active in experienced meditators than in non-meditators (Baerentsen 2010, Chiesa 2010). Key studies identifying structural and functional changes in the brains of meditators are summarized in Table 1.

Although many brain regions and networks appear to respond neuroplastically to various methods of meditation, consistent patterns of regional brain activation and their clinical meaningfulness in the management of ADHD remain to be clearly elucidated. Preliminary research supports a potential therapeutic role in improving cognitive deficits and improving self-regulation in children and adults with ADHD. Two unpublished pilot studies

(n = 23 and 24) reported behavioural improvement in ADHD children 12 years of age and younger who received individual meditation training (Moretti-Altuna 1987, Zylowska 2008, citing: Kratter 1983). In the Kratter study (1983), a graduate thesis project, male students (mean age 7-12 yrs) who met DSM-III criteria for ADHD were randomly assigned to either receive twice-weekly sessions increasing from two to eight minutes of meditation training (MT) per session for four wks; or progressive muscle relaxation training (RT) at the same frequency as MT; or were placed on a waiting list for four weeks (control group), after which they received meditation training identical to the experimental group. Both MT and RT groups showed significant improvement in impulsivity when faced with a problem-solving task, as measured by the Matching Familiar Figures Test (MFFT).

Only the meditation groups showed improved selective attention ability, as assessed by the Fruit Distraction Test (FDT). Parental assessment scores also indicated significantly improved homework performance and at-home behaviour (Kratter 1983). These pilot studies were not peer-reviewed and were subject to the limitations of relatively small participant group sizes (Kratter 1983).

More recently, Zylowska and colleagues (2008) conducted an open-label study examining the feasibility of mindfulness

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FEATURE Meditation and ADHD

meditation training for individuals with ADHD (n=8 adolescents and n=24 adults). Following the eight-week meditation program participants showed symptomatic and attentional process improvement (Zylowska 2008). As cited in Zylowska (2008), the meditation training was based on the work of Kabat-Zinn (1990) and Segal et al. (2002) with adaptations to address the unique challenges of ADHD. For example, sitting periods were shortened; walking meditation could be substituted for sitting meditation; and each session was concluded with a loving-kindness meditation to help address the low self-esteem issues often associated with ADHD. Participants attended six to eight weekly group sessions of 2.5 hours each, including meditation exercises and a psychoeducational component that reframed the “deficit” aspects of ADHD as “neurobiological differences”. The adolescents also practiced at home for an average of 42.6 minutes over four days per week. Assessment of neurocognitive performance and self-reported symptom scales indicated a statistically significant symptom reduction for adolescents and adults (pooled data), with 30% of participants reporting a symtomatic reduction of at least 30%. Neurocognitive findings suggested that meditation improved attention, inhibition and self-regulation, which are key deficits in ADHD (Zylowska 2008). Among the adolescent participants of this study, 75% reported a lifetime history of at least one psychiatric comorbidity, most commonly depression (25.1%). Meditation was associated with significant improvements in depression (p<0.01) and anxiety (p<0.02) scores among adults, but not among adolescents. However, the small adolescent sample size precluded meaningful statistical analysis (Zylowska 2008).

This pilot study supported the feasibility of an ADHD-adapted mindfulness meditation program to reduce self-reported symptoms and improve neurocognitive performance in adults and

adolescents, with 78% treatment adherence, very high participant satisfaction and no adverse events.

Supplementary, unpublished data from the same study indicated significant improvements in perceived stress and mindfulness (p<0.01) (Zylowska 2009). Participants reported additional improvements in ADHD symptoms with no changes in anxiety, depression, stress or mindfulness at three-months post-intervention follow-up (Zylowska 2009). It was noted that the social support provided by the group setting and the psychoeducational component may have contributed to the overall positive results (Zylowska 2008). According to study recruitment data, more individuals who wished to participate were prevented from doing so due to scheduling restrictions, suggesting that ease of program access and schedule flexibility may be critical when offering this type of group training (Zylowska 2008).

No adverse events have been reported with the use of meditation in the treatment of ADHD in children or adults (Krisanaprakornkit 2010).

Yoga in the Treatment of ADHD

Yoga is a non-religious, traditional practice that incorporates meditation with training in breathing techniques, physical postures and relaxation (Jensen 2004). It has been used in the treatment of ADHD (Brown 2005, Jensen 2004). In a crossover study by Jensen and Kenny (2004), boys (8-13 years of age) who had been diagnosed with ADHD by a pediatrician participated in a 20-session yoga training (n=11) or cooperative games (n=8).

All but two of the boys (who did not require medication) were symptomatically stabilized by medication during school hours.

Table 2: Summary of Studies using Mind-Body Therapies in the Treatment of ADHD Authors

Participants

Treatment Activity

Outcomes

Zylowska 2008

(n=8) adolescents and (n=24) adults with ADHD

Six to eight weekly group sessions of 2.5 hours each, including meditation and psychoeducation; meditation also variably practiced at home

Significant (p<0.01) reductions in self-reported ADHD, anxiety and depressive symptoms, conflict attention and attentional set-shifting

Jensen 2004

Boys (8-13 y) diagnosed with ADHD (n=19)

One-hour group yoga training weekly for 20 weeks (n=11) or cooperative games (n=8)

Yoga group showed significant improvement in primary ADHD behaviours of restlessness, impulsivity and inattentiveness; reduced emotional lability; more controllable behaviour at home and improved ability to maintain focus on activities

Moretti-Altuna 1987 (as reviewed in Zylowska 2008)

(n=24) boys diagnosed with ADHD

Four-wk transcendental meditation (TM) training

Significant decrease in disruptive classroom behaviour (unpublished)

Kratten 1983

(n=24) boys (age 7-12 yrs) meeting DSM-III criteria for ADHD

Randomly assigned to meditation training (MT), relaxation training (RT) or waiting list control (WLC)

Significantly improved selective deployment of attention with MT; decreased impulsivity in both MT and RT compared to controls (unpublished graduate thesis) ihpmagazine.com { October 2011 IHP | 81

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FEATURE Meditation and ADHD

They were assessed by teachers at school, and by their parents during unmedicated periods (mornings and weekends) at home. Group yoga sessions occurred weekly for one hour and participants were also encouraged to practice at home. The yoga practice included training in concentration, breathing technique, static yoga postures and relaxation. The yoga group showed significant improvement in primary ADHD behaviours of restlessness, impulsivity and inattentiveness; and reduced mood swings, temper outbursts and crying fits as per the Conner’s Global Emotional Lability Index.

Based on ADHD Index scoring, parents of children in the yoga group reported significantly more controllable behaviour and improved ability to keep focused on activities. Only the control group showed significant positive changes in anxiety, shyness and social problems, hyperactivity and perfectionism. Limitations of the study included significant differences between yoga and cooperative games groups despite randomization; inability to control the quality, duration and frequency of yoga practice at home; and the allocation of four times more contact time to the yoga group than controls, due to resource constraints (Jensen 2004).

Implications for Integrative Practice

References American Psychiatric Association (APA). Diagnostic and statistical manual of mental disorders (4th ed.). 1994. Washington, D.C.

Kuhlmann B, (ed.). Institute for Clinical Systems Improvement (ICSI). Diagnosis and management of attention deficit hyperactivity disorder in primary care for school-age children and adolescents. 2010 (Eighth Edition).

American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Accessed electronically at: http://www.cdc.gov/ncbddd/adhd/ diagnosis.html

Luders E, Clark K, Narr KL, et al. Enhanced brain connectivity in long-term meditation practitioners. NeuroImage 2011;57:1308-1316.

Baerentsen KB, Stodkilde-Jorgensen H, Sommerlund B, et al. An investigation of brain processes supporting meditation. Cogn Process 2010;11:57-84.

Baijal S, Gupta R. Meditation-based training: a possible intervention for attention deficit hyperactivity disorder. Psychiatry (Edgmont) 2008;5(4):48-55.

Brown KA, Patel DR. Complementary and alternative medicine in developmental disabilities. Ind J Pediatrics 2005:72:949-952.

Chan E, Rappaport LA, Kemper KJ. Complementary and alternative therapies in childhood attention and hyperactivity problems. Dev Behav Pediatr 2003;24(1):4-8.

Chiesa A, Serretti A. A systematic review of neurobiological and clinical features of mindfulness meditations. Psychological Medicine 2010;40:1239-1252.

Foisy, M. and Williams, K. The Cochrane review and non-pharmacological treatments for attention deficit hyperactivity disorder in children and adolescents: an overview of reviews. Evidence-Based Child Health: A Cochrane Review Journal, 2011;6:283–297.

Jensen PS, Kenny DT. The effects of yoga on the attention and behaviour of boys with attention-deficit/hyperactivity disorder (ADHD). J Atten Disord 2004;7(4):205-215.

Kratter J, Hogan JD. The use of meditation in the treatment of attention deficit disorder with hyperactivity. Dissertation Abstracts International 1983;44:[pages unknown]. Accessed electronically on 15 Aug 2011 at: http://www. livingwisdomschool.org/howtoapply/qs-pars-ask/research/Meditation%20in%20 the%20Treatment%20of%20ADHD.pdf Krisanaprakornkit T, Ngamjarus C, Witoonchart C, Piyavhatkul N. Meditation therapies for attention- deficit/hyperactivity disorder (ADHD). Cochrane Database of Systematic Reviews 2010, Issue 6. Art. No.: CD006507. DOI: 10.1002/14651858.CD006507.pub2.

Meditation and yoga have been used safely in conjunction with conventional care for ADHD in preliminary trials. Extensive neuroimaging data indicate meditation-induced neuroplasticity as a plausible explanation for the apparent attentional, emotional and self-regulatory benefits of meditation practice. Limitations to the currently available evidence for the use of meditation in ADHD treatment include relatively small study populations and lack of adequate statistical power (Foisy 2011, Zylowska 2008); reliance on self-reported data (Zylowska 2008); risk of bias (Krisanaprakornkit 2010); lack of standardized assessment standards (Foisy 2011); and uncertainty as to whether the observed neuroplastic effects of meditation in healthy individuals are clinically applicable to those with ADHD (Baijal 2008). Larger, controlled trials are needed to further characterize the therapeutic value of meditation and yoga in children and adults with ADHD, but these are relatively safe, inexpensive therapies that can be readily integrated into a multimodal treatment plan as supported by positive preliminary clinical and neurobiological evidence. •

Lutz A, Slagter HA, Dunne JD, et al. Attention regulation and monitoring in meditation. Trends Cogn Sci 2008;12(4):163-169.

Manna A, Raffone A, Perrucci MG, et al. Neural correlates of focused attention and cognitive monitoring in meditation. Brain Res Bull 2010;82:46-56.

Moretti-Altuna G. The effects of meditation versus medication in the treatment of attention deficit hyperactivity disorder. Dissertation Abstracts International 1987;47:4658. (As cited in Zylowska 2008).

Raffone A, Srinivasan N. The exploration of meditation in the neuroscience of attention and consciousness. Cogn Process 2010:11:1-7.

Sinha D, Efron D. Complementary and alternative medicine use in children with attention deficit hyperactivity disorder. J Paediatr Child Health 2005;41(23-26).

Slatger HA, Lutz A, Greischer LL, et al. Mental training affects distribution of limited brain resources. PLoS Biol 2007;5(6):1228-1235.

Szymanski M, Zolotor A. Attention-deficit/hyperactivity disorder: management. Am Fam Physician 2001;64:1355-1362.

Tang Y, Lu Q, Geng X, et al. Short-term meditation induces white matter changes in the anterior cingulate. Proc Nat Acad Sci 2010;107(35):15649-15652.

Vestergaard-Poulsen P, van Beek M, Skewes M, et al. Long-term meditation is associated with increased gray matter density in the brain stem. NeuroReport 2009;20:170-174.

Wahbeh H, Elsas S-M, Oken BS. Mind-body interventions: applications in neurology.

Neurology 2008;70:2321-2328.

Zylowska L, Ackerman DL, Yang MH, et al. Mindfulness meditation training in adults and adolescents with ADHD: a feasibility study. J Atten Disord 2008;11(6):737-746.

Zylowska L, Smalley SL, Schwartz JM. Mindful awareness and ADHD. Clinical Handbook of Mindfulness 2009;43:319-338.

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TM

For Details, write #114 on Free Info Page, page 96.

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PRODUCT mOnOgRaPh

PRODUCT MONOGRAPH OIL OF OREGANO

Oil of Oregano is a hydrophobic extract of Origanum vulgare leaf. Major active constituents include the monoterpene phenolic compounds carvacrol and thymol. Carvacrol and thymol are potent antimicrobials with synergistic bactericidal, fungicidal, and antihelminthic activity.

Human studies

Oil of Mediterranean Oregano had antihelminthic effects when given at 600 mg emulsified oil per day in 14 adults who had tested positive for enteric parasites Blastocystis hominis, Entamoeba hartmanni, and Endolimax nana. After 6 weeks of treatment, there was complete resolution of parasitic infection in 8 cases, while Blastocystis hominis scores decreased in three more cases; gastrointestinal symptoms improved in 7 of the 11 subjects who had presented with Blastocystis hominis infection. (Force 2000)

Animal and In vitro studies

Carvacrol for oral candidiasis in immunocompromised rats was found to be as effective as treatment with Nystatin, reducing the number of colony forming units (CFU’s) and completely clearing hyphae from oral surfaces when given for 8 days (Chami 2004). In vitro, carvacrol was determined to exert an inhibitory effect against 6 different strains of Candida species primarily due to extensive lesion of the plasma membrane (Salgueiro 2003).

Carvacrol has potent antimicrobial activity against several microbial species, including Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Psuedomonas aeruginosa, Candida albicans, and Aspergillus niger; out of these, Candida albicans has been found most susceptible (Santoyo 2006). Carvacrol and thymol are thought to exert an additive effect by disrupting bacterial membrane integrity (Lambert 2001). Oregano has been shown to inhibit Methicillin resistant strains of Staph.

Figure 1: Structure of Carvacrol (left) and Thymol (right)

aureus and epidermis, and attenuates biofilm formation in vitro (Nostra 2004; 2007).

Toxicology

Essential oil extracts are categorically known to be toxic in high doses, and are therefore typically given in drop doses; essential oils should not be used internally by pregnant or breastfeeding women. Animal studies to date, however, indicate relative safety of Oregano oil.

Carvacrol was shown to be hepatoprotective against ischemia and reperfusion injury in rats; both carvacrol and silymarin had similar beneficial effects on AST and ALT levels (Canbek 2007). Carvacrol also increased liver regeneration rate in rats after partial hepatectomy (Uyanoglu 2008).

Mutagenicity studies of carvacrol show only weak activity; carvacrol is excreted in urine after 24 hours in large quantities, unchanged or as glucoronide and sulphate conjugates (De Vincenzi 2004).

References

Canbek M, Uyanoglu M, Bayramoglu G, Senturk H, Erkasap N, Koken T, Uslu S, Demirustu C, Aral E, Husnu Can Baser K. Effects of carvacrol on defects of ischemia-reperfusion in the rat liver. Phytomedicine. 2008 Jan. De Vincenzia M et al. Constituents of aromatic plants: carvacrol. Fitoterapia 2004; 75(7-8): 801-804.

Force M et al. Inhibition of enteric parasites by emulsified oil of oregano in vivo. Phytother Res. 2000 May;14(3):213-4.

Lambert RJ, Skandamis PN, Coote PJ, Nychas GJ. A study of the minimum inhibitory concentration and mode of action of oregano essential oil, thymol and carvacrol. J Appl Microbiol. 2001 Sep;91(3):453-62.

Nostro A, Roccaro AS, Bisignano G, Marino A, Cannatelli MA, Pizzimenti FC, Cioni PL, Procopio F, Blanco AR. Effects of oregano, carvacrol and thymol on Staphylococcus aureus and Staphylococcus epidermidis biofilms. J Med Microbiol.

2007;56(Pt 4):519-23.

Nostro A et al. Susceptibility of methicillin-resistant staphylococci to oregano essential oil, carvacrol and thymol. FEMS Microbiol Lett. 2004;230(2):191-5.

Salgueiro LR et al. Chemical composition and antifungal activity of the essential oil of Origanum virens on Candida species.

Planta Med. 2003 Sep;69(9):871-4.

Santoyo S, Cavero S, Jaime L, Ibañez E, Señoráns FJ, Reglero G. Supercritical carbon dioxide extraction of compounds with antimicrobial activity from Origanum vulgare L.: determination of optimal extraction parameters. J Food Prot.

2006;69(2):369-75.

Uyanoglu M, Canbed M, Aral E, Husnu Can Baser K. Effects of carvacrol upon the liver of rats undergoing partial hepatectomy. Phytomedicine 2008; 15(3): 226-9. ihpSept10_NAHS_Ad.indd 2 058.IHP NAHS mono.indd 1

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Integrated Healthcare Practitionersâ&#x20AC;&#x2122; Dietary and Nutritional Supplement, and Herbal Remedies Management Program Author: Christopher Habib, ND successful completion of the questions at the end of this paper has been approved for continuing education by the bddt-n ; 1.0 credit general and by the cnpbc ; one ce hour.

Mammography for Breast Cancer Screening An update of the evidence

Introduction

Breast cancer is the most common noncutaneous cancer among Canadian women. Current statistics show that one in nine women is expected to develop breast cancer during her lifetime and one in 29 will die of it (Canadian Cancer Society 2011). Research indicates that mortality rates of breast cancer have been steadily declining in past decades, especially in women under the age of 50 (Shen 2011).

This has been attributed to many factors, including the widespread use of screening mammography. In the past, both Europe and North America have provided strong evidence in the form of meta-analyses that have supported the use of mammography in the reduction of breast cancer mortality (Kerlikowske 1995). These studies have suggested a wide range of impact from a reduction of 42% to an increase of 2% in mortality (Gøtzsche 2011).

However, more recent systematic reviews have shown that a substantial bias was present in the earlier studies. The differences in reported reductions in breast cancer mortality could not be explained by screening effectiveness and screening appeared to be ineffective (Gøtzsche 2011). This led to important changes in screening guidelines. In 2009, the United States Preventive Services Task Force (USPSTF) released new recommendations advising against screening mammography for women before the age of 50. The science behind these recommendations has been challenged and notable controversy on the topic continues today among researchers and policy-makers (Hendrick 2011). Hendrick argues that the evidence made available to the USPSTF supports

screening beginning at age 40, while the potential harms are minor (Hendrick 2011). Consequently, it is difficult for clinicians to advise their patients in an informed fashion. This paper reviews the most recent and strongest evidence available to help educate clinicians.

Current Canadian Guidelines

The recommendations on screening mammography provided by the Canadian government and the Canadian Cancer Society are equivalent. Provincial guidelines such as those provided by Cancer Care Ontario follow the same national guidelines. These guidelines are stratified by age. Women aged 40 to 49 are advised to talk to their doctors regarding their risk of breast cancer and the risks and benefits of mammography. Routine mammography for women of average risk is discouraged. Women aged 50 to 69 are advised to have a mammogram every two years. Women aged 70 or older are advised to talk to their doctors to determine how often to have a mammogram. Screening above the age of 74 is not recommended as the risks outweigh the possible benefits (Health Canada 2011).

Christopher Habib, BSc(Hons), ND Research Resident Canadian College of Naturopathic Medicine 1255 Sheppard Avenue East Toronto, ON M2K 1E2 chabib@ccnm.edu

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If you are:

You should:

40 to 49

Talk to your doctor about your risk of breast cancer, along with the benefits and risks of mammography.

50 to 69

Have a mammogram every 2 years.

70 or older

Talk to your doctor about how often you should have a mammogram.

For women between the ages of 30 and 69 at high risk of breast cancer, the chances of getting breast cancer are two to five times higher than in the general population. For this reason, guidelines recommend that women at high risk obtain yearly screening using both a mammogram and Magnetic Resonance Imaging (MRI). MRI has been shown to be significantly more sensitive than mammography and breast ultrasound in high-risk populations, especially in women with dense breast tissue (Le-Petross 2011). However, MRI is limited by its cost and availability and would lead to higher false positive rates.

The American Cancer Society considered there to be insufficient evidence to recommend for or against screening with MRI for women with a personal history of breast cancer, carcinoma in situ, atypical hyperplasia, and extremely dense breasts on mammography (Gemingnani 2011). Instead, they recommend screening MRI for women with an approximately 20% to 25% or greater lifetime risk of developing breast cancer (Saslow 2007).

In Canada, women are considered at high risk if they fall into one of the following categories: • If they have already completed genetic testing for breast cancer and have received confirmation of a genetic mutation that increases breast cancer risk, such as BRCA1, BRCA2 or TP53.

• If they have not completed genetic testing themselves, but have a parent, sibling, or child with confirmation of a genetic mutation.

• If they have a family history that indicates hereditary breast cancer syndrome and who have a greater than or equal to 25% lifetime risk of breast cancer confirmed through genetic counselling.

• If they have received radiation therapy to the chest before 30 years of age as a treatment for another cancer or condition, such as Hodgkin’s disease (Health Canada 2011).

Pros and Cons of Mammography

Benefits 1) Detecting cancer (true positives). The sooner cancer is detected, the better the chances of survival. In other words,

the earlier a cancer is found, the earlier it can be treated.

Early detection usually implies that less treatment is required and a faster recovery time since the cancers that are detected sooner will likely be smaller and be less likely to have nodal involvement. Overall, this results in a reduction in morbidity and mortality for cancer patients, with the greatest benefit seen in high risk populations. The range of true positives for mammography in clinical trials is from 83% to 95% (Mushlin 1998).

2) Providing reassurance (true negatives). Many people prefer to have routine examinations to feel confident they are in good health. A negative mammogram can help reduce anxiety about suspicious breast lumps, or reduce fears that there is an underlying cancer that is going undetected.

3) Easily accessible and cost-effective. Mammograms currently play a central role in detecting breast cancers in the health care system. Mammograms do not massively tax health care resources. Mammograms may also exclude the need to obtain an alternative method of screening.

Continuing Education Lesson

Health Canada Screening Mammography Recommendations (Health Canada 2011)

Risks 1) False positives. This occurs when the results of the mammogram suggest cancer even when none is present. This can result in unnecessary and painful invasive testing with biopsy and unnecessary psychological distress. These potential results are most applicable to women below the age of 50, where the false positive rates can be as high as 56% (Elmore 1998).

In a small cohort of women, distress levels are heightened to worrying levels that may have long-term implications (Montgomery 2010).

2) False negatives. This is when cancer is not detected even though it is present. This can cause a false sense of reassurance and delay diagnosis and treatment.

3) Over-diagnosis and over-treatment. Certain cancers are not life-threatening, do not cause symptoms, and do not impact quality of life. Diagnosing and treating these cancers is unnecessary and there is no advantage in doing so. This may lead to needless testing, treatments, anxiety, and the consumption of resources. A meta-analysis reported the rate of over-diagnosis to be as high as 52% (Jorgensen 2009). ihpmagazine.com { October 2011 IHP | 87

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Continuing Education Lesson 4) Increased exposure to radiation. X-rays used in mammography can have a negative influence on health and may increase the risk of cancer after cumulative exposure. However, it is thought that the improvements in technology make this risk minimal nowadays (Feig 1997).

The Evidence

The USPSTF recommends biennial screening for women aged 50 to 74 and advises against routine screening for women below the age of 50 or above the age of 74. On the basis of their systematic review, they also recommend against teaching self-breast exams (SBE) or utilizing clinical breast exams (CBE). The evidence shows that these recommendations help minimize the risks associated with mammography and that any additional testing, as with SBE or CBE do not confer benefits in addition to mammography (Nelson 2009). The USPSTF recommendation statement comes from an independent panel of public health experts and is based on an analytic framework that focuses on mortality as the primary outcome measure (Barton 2007). They believe there is an overwhelming consensus among advocacy groups to screen and that the discrepancy lies in the finer implementation of issues regarding what age groups should be screened and how often.

Most international screening programs have adopted the same guidelines as the USPSTF (Gregory 2010).

Contrary to the most current USPSTF recommendations, some have argued that annual screening beginning at age 40 is justified (Hendrick 2011). One argument is that in making their decision, the USPSTF rejected all peer-reviewed studies that were not randomized controlled trials using mortality as the outcome measure. This meant the exclusion of a large number of studies which could have presented differing evidence. These authors also argue that annual screening for women 40 to 84 years old is estimated to convey a 39.6% mortality reduction, whereas biennial screening at ages 50 to 74 years is estimated to convey only a 23.2% mortality reduction. A recent retrospective study of the Cancer Registry Database in Missouri also showed similar results for the 40 to 49 age group, with a 19% increase in survival for those who had mammographically detected breast cancer versus those who had non-mammographically detected breast cancer (Shen 2011).

The issue of whether or not additional screening confers benefit is contested. In Europe, a large retrospective study showed that

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Continuing Education Lesson

screening did not play a direct part in the reduction of breast cancer mortality (Autier 2011). The decrease in mortality was thought to reflect a combination of decreased use of menopausal hormone therapy and delayed diagnosis because of a decrease in utilization of mammography screening (Gemignani 2011).

However, the issue that is perhaps more important is whether or not the magnitude of any benefit outweighs the potential harms and warrants mass screening for the general population.

The absolute risk of developing breast cancer for women in their forties is low compared with other age groups (Gemignani 2011).

The USPSTF estimated that it would require 1904 women of ages 40 to 49 years to save one life and concluded that the degree of harm in this age group outweighed the benefit (Hendrick 2011). This data is similar to the analyses done by the Cochrane Collaboration.

Ten years ago, the Cochrane Collaboration released a systematic review of screening for breast cancer with mammography. They analyzed seven randomized controlled trials that included half a million women. They concluded that the available evidence at the time did not show a survival benefit for mass screening of breast cancer (Gøtzsche 2001). This systematic review has been updated

every few years and the most recent version published in 2011 provides some of the most up-to-date information on the subject.

The latest review analyzed eight randomized controlled trials and included 600 000 women. Although not all trials had adequate randomization, the ones that did showed no effect of screening on cancer mortality, including breast cancer, after 10 years (RR 1.02, 95% CI 0.95 to 1.10) or on all-cause mortality after 13 years (RR 0.99, 95% CI 0.95 to 1.03). The number of lumpectomies and mastectomies performed, as well as the use of radiotherapy, was significantly larger in the screened groups (Gøtzsche 2011).

The authors concluded that screening is likely to reduce breast cancer mortality, but that the reduction is estimated at 15% or an absolute risk reduction of 0.05%. Screening led to 30% over-diagnosis and over-treatment or an absolute risk increase of 0.5%. This means that for every 2000 women who undergo mammography screenings during a 10 year period, one will have her life prolonged and 10 will be treated unnecessarily.

In addition, more than 200 women will experience significant psychological distress for numerous months because of the false positive findings. Seen under this light, it is not clear whether mammography does more good than harm (Gøtzsche 2011). ihpmagazine.com { October 2011 IHP | 89

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Continuing Education Lesson

It is imperative that clinicians stratify patients according to individual risk by taking a thorough history and using information

such as patient age, age at menarche, child-bearing status, and breast density to minimize false-positives (Murphy 2010). If a patient has several risk factors or strong predictive risk factors, making the decision to screen becomes simpler. It is also of vital importance that clinicians educate their patients and communicate effectively the risks and benefits of screening mammography. To be able to do this, it is essential that clinicians have a thorough understanding of the most up-to-date research and statistics (Hirsch 2011). Finally, clinicians must have an understanding of the alternatives to mammography, including CBE, SBE, MRI, breast ultrasound, thermography, etc. Every screening test has its limitations, but they are constantly improving and some form of testing is key to err on the side of caution. The most appropriate screening strategy is still best determined for each individual patient. Further research is needed to clarify exactly under what circumstances mammography would be most appropriate. •

References Autier P, Boniol M, Gavin A, Vatten LJ. Breast cancer mortality in neighbouring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database. BMJ 2011;343:d4411.

Jorgensen KJ and Gotzsche. Over diagnosis in publicly organized mammography screening programmes: systematic review of incidence trends. BMJ. 2009; 339:b2587.

Conclusion

The question of whether or not to screen for breast cancer with mammography is a difficult one to answer conclusively. The most educated answer for clinicians at this point in time may be “it depends.” Breast cancer causes significant morbidity and mortality and all advocacy groups recommend screening schedules in some form. However, some of the largest and most powerful research suggests that the benefit of mammography may be minimal and that the harm caused may outweigh any advantages (Gøtzsche 2011). There is agreement among clinicians that breast cancer screening has potential benefits and potential harms and the largest obstacle is determining how to appropriately guide patients using evidence-based recommendations.

Barton MB, Miller T, Wolff T, Petitti D, LeFevre M, Sawaya G, Yawn B, GuirguisBlake J, Calonge N, Harris R, U.S. Preventive Services Task Force. How to read the new recommendation statement: methods update from the U.S. Preventive Services Task Force. Ann Intern Med 2007; 147:123–127.

Canadian Cancer Society. Canada-wide Breast Cancer Statistics. Available: http:// www.cancer.ca/Canada-wide/About%20cancer/Cancer%20statistics/Stats%20 at%20a%20glance/Breast%20cancer.aspx?sc_lang=en [accessed August 29, 2011].

Elmore JG, Barton MB, Moceri VM, Polk S, Arena PJ, Fletcher SW. Ten-year risk of false positive screening mammograms and clinical breast examinations. N Engl J Med 1998;338(16):1089–96.

Feig SA and Hendrick RE. Radiation risk from screening mammography of women aged 40-49 years. J Natl Cancer Inst Monogr. 1997;22:119–124.

Gemignani ML. Breast Cancer Screening: Why, When, and How Many? Clinical Obstetrics and Gynecology. 2011; 54(1): 125-132.

Gøtzsche PC. Relation between breast cancer mortality and screening effectiveness: systematic review of the mammography trials. Danish Medical Bulletin. 2011 March; 58(3):A4246.

Gøtzsche PC and Nielsen M. Screening for breast cancer with mammography.

Cochrane Database Syst Rev. 2011 Jan 19;(1):CD001877.

Gøtzsche PC and Olsen O. Screening for breast cancer with mammography.

Cochrane Database Syst Rev. 2001;(4):CD001877.

Gregory KD and Sawaya GF. Updated recommendations for breast cancer screening. Current Opinion in Obstetrics and Gynecology. 2010; 22:498–505.

Health Canada. Mammography: When to have a Mammogram. Available: http:// www.hc-sc.gc.ca/hl-vs/iyh-vsv/med/mammog-eng.php [Accessed August 29, 2011].

Hendrick RE and Helvie MA. United States Preventive Services Task Force Screening Mammography Recommendations: Science Ignored. AJR. 2011 Feb; 196:W112-W116.

Hirsch B and Lyman GH. Breast Cancer Screening with Mammography. Curr Oncol Rep 2011; 13:63–70.

Kerlikowske K, Grady D, Rubin SM, Sandrock C, Ernster VL. Efficacy of screening mammography. A meta-analysis. JAMA. 1995;273(2):149-154.

Le-Petross HT and Shetty MK. Magnetic Resonance Imaging and Breast Ultrasonography as an Adjunct to Mammographic Screening in High-Risk Patients.

Semin Ultrasound CT MRI. 2011; 32:266-272.

Montgomery M and McCrone SH. Psychological distress associated with the diagnostic phase for suspected breast cancer: systematic review. Journal of Advanced Nursing. 2010; 66(11), 2372–2390.

Murphy, A.M. Mammography screening for breast cancer: a view from 2 worlds.

JAMA. 2010; 303(2): 166-7.

Mushlin AI, Kouides RW, Shapiro DE. Estimating the accuracy of screening mammography: a meta-analysis. Am J Prev Med. 1998;14(2):143–153.

Nelson HD, Tyne K, Naik A, Bougatsos C, Chan BK, Humphrey L, U.S. Preventive Services Task Force. Screening for breast cancer: an update for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151: 727–737, W237–W242.

Nelson HD, Tyne K, Naik A, Bougatsos C, Chan B, Nygren P, Humphrey L. Screening for breast cancer: systematic evidence review update for the U.S. Preventive Services Task Force. Evidence Review Update No. 74. AHRQ Publication No. 10-05142-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2009.

Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, Morris E, Pisano E, Schnall M, Sener S, Smith RA, Warner E, Yaffe M, Andrews KS, Russel CA, American Cancer Society Breast Cancer Advisory Group. American Cancer Society guidelines for breast screening with MRI as an adjunct tomammography.CA Cancer JClin. 2007;57:75–89. Erratum in: CA Cancer J Clin. 2007;57:185.

Shen N, Hammonds LS, Madsen D, Dale P. Mammography in 40-Year-Old Women: What Difference Does It Make? The Potential Impact of the U.S. Preventative Services Task Force (USPSTF) Mammography Guidelines. Ann Surg Oncol 2011 Aug; DOI 10.1245/s10434-011-2009-4.

Tabar L, Vitak B, Chen HH, Yen MF, Duffy SW, Smith RA. Beyond randomized controlled trials: organized mammographic screening substantially reduces breast carcinoma mortality. Cancer. 2001;91:1724–31.

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1. Mammography is significantly more sensitive than magnetic resonance imaging (MRI) in high-risk populations. a) True b) False 2. Health Canadaâ&#x20AC;&#x2122;s guidelines on recommending mammography for breast screening do NOT include: a) Women aged 40 to 49 are advised to talk to their doctors regarding their risk of breast cancer and routine mammography is encouraged for women of average risk. b) Women aged 50 to 69 are advised to have a mammogram every 2 years. c) Women aged 70 or older are advised to talk to their doctors to determine frequency of mammography screening. d) Screening above the age of 74 is not recommended.

3. False positive results are most applicable to women above the age of 50. a) True b) False 4. The United States Preventive Services Task Force recommends the following: a) Biennial screening for women aged 50 to 74 b) Routine screening for women below the age of 50 and above the age of 74. c) Teaching self-breast exams and utilizing clinical breast exams. d) A and C 5. Which of the following statements is true regarding the pros of mammography: a) Mammograms can detect cancer and the sooner cancer is detected, the better the chances of survival. b) Mammograms can reduce anxiety about suspicious breast lumps or undetected cancer. c) Mammograms are easily accessible and cost-effective. d) Mammograms may exclude the need to obtain an alternative method of screening. e) All of the above.

6. In Canada, women are considered at high risk for breast cancer if they fall into which category: a)If they have completed genetic testing for breast cancer and have received confirmation of a genetic mutation that increases breast cancer risk.

b) If they have a parent, sibling, or child with confirmation of a genetic mutation. c) If they have received radiation therapy to the chest before 20 years of age as a treatment for another cancer or condition. d) Two of the above. e) Three of the above.

7. Which of the following statements are true based on the Cochrane Collaboration systematic reviews of screening for breast cancer with mammography: a) The available evidence at the time does not show a survival benefit for mass screening of breast cancer. b) No effect of screening on cancer mortality after 10 years was found in studies that had adequate randomization. c) No effect of screening on all-cause mortality after 13 years was found in studies that had adequate randomization. d) The number of lumpectomies and mastectomies performed, as well as the use of radiotherapy, was significantly larger in the screened groups. e) All of the above 8. Which of the following statements is false regarding the cons of mammography: a) False positives occur when the results of the mammogram suggest cancer even when none is present. b) False negatives occur when cancer is not detected even though it is present. This can cause a false sense of reassurance and delay diagnosis and treatment. c) False positives can cause a false sense of reassurance and delay diagnosis and treatment. d) Mammograms can lead to over-diagnosis and over-treatment. e) Mammograms can cause increased exposure to radiation.

Continuing Education Lesson

Questions

9. Over-diagnosis has been reported to be higher than 50% . a) True b) False 10. The authors of the Cochrane Collaboration systematic review of screening for breast cancer did NOT make the following conclusion: a) Screening is unlikely to reduce breast cancer mortality. b) Screening led to a 15% reduction of breast cancer mortality. c) Screening led to 30% over-diagnosis and over-treatment. d) The authors of the Cochrane Collaboration concluded all of the above statements.

Fax or email answers to: 416.703.6392 or philip@ihpmagazine.com Name: Address:

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Email:

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Calendar Events

October October 21-22 Toronto Neurology Update 2011 Organized by: Office of Continuing Education and Professional Development, University of Toronto Toronto, Ontario For more information, visit events.cepdtoronto.ca/website/ index/MED1124 October 21-23 Certificate in Primary Care Skin Cancer Medicine Organized by: American Academy of Anti-Aging Medicine Atlanta, Georgia For more information, visit http://www.worldhealth.net/skincancer/ October 22-23 BioFlex Low-Intensity Laser Therapy Certification Training Course Organized by: Meditech, International TBA, British Columbia For more information, visit http://www.meditech-bioflex.com October 22-23 2011 Maritime Convention Hosted by: New Brunswick Chiropractic Association Fredericton, New Brunswick For more information, visit http://www.nbchiropractic.ca October 22–26 Canadian Cardiovascular Congress Organized by: Canadian Cardiovascular Society Vancouver, British Columbia For more information, visit http://www.cardiocongress.org/ October 28 7th Annual Everyday Gynaecology: The Management of Common Gynaecologic Conditions (formerly Gynaecology Review Day) Toronto, Ontario Organized by: Mount Sinai Hospital For more information, visit http://www.mountsinai.on.ca/ education October 29-30 Graston Technique MI (Basic Training) and M2 (Advanced Training) Organized by: Graston Technique/TherapyCare Resources Inc. Toronto, Ontario For more information visit http://www.grastontechnique.com/ EducationTraining/TrainingSchedule.html

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CONGRATULATIONS! Dr. Marja Verhoef, Calgary, Alberta Recipient of the Third $250,000 Dr. Rogers Prize for Excellence in Complementary and Alternative Medicine

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Dr. Marja Verhoef, Calgary, Alberta

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PRODUCT MONOGRAPH

Introduction: fast joint care+ by Genuine Health is a novel, rapidly acting formulation designed to help alleviate joint pain and stiffness. fast joint care+ is a patented ingredient containing naturally occurring combination of molecules derived from natural eggshell membrane (NEM), Gallus gallus. These molecules include fibrous proteins such as collagen type I, glycosaminoglycans (GAGs) such as chondroitin sulfate and dermatan sulfate, sulfated glycoproteins such as glucosamine, hyaluronic acid, and a host of other related proteins (Ruff 2009a). fast joint care+ is unique as a joint care product. Unlike the most commonly used medications for the condition, such as NSAIDs, NEM is a disease-modifying agent, meaning that it not only improves the symptoms of arthritis but also helps repair damaged tissue. NSAIDs carry significant risks, such as development of peptic ulcer disease, renal failure, and hemorrhage; underscore the importance of developing safe treatment alternatives (Vangsness 2009). Unlike the natural alternatives glucosamine and chondroitin sulfate that can take several weeks to act, NEM works within 7-10 days.

Osteoarthritis: Osteoarthritis (OA) is the most common musculoskeletal condition in Westernized countries; approximately 27 million Americans are estimated to be clinically diagnosed with OA, while upwards of 46 million are thought to be affected by arthritis as a non-specific category (Vangsness 2009, Lawrence 2008, Theis 2007). This is to say nothing of the millions suffering from undiagnosed arthritis and other types of degenerative joint diseases.

The impact of OA includes pain, loss of function and mobility, physical and psychosocial disability, complications of NSAID therapy, and financial costs to the healthcare system.

Recent estimates of national (US) medical expenditures approximate 81 billion dollars, while earnings losses approximate 47 billion annually, attributable to OA or other rheumatic conditions (AORC). Direct average annual per person medical expenditures due to AORC ranged from $1454- 2206. (Theis 2007) Research: Two initial pilot studies involving 11 and 26 subjects respectively with pre-existing joint disorders found significant reductions in joint pain, joint stiffness, and pain on range of motion (ROM) compared to baseline (Ruff 2009a). After 7 days there was a 25% reduction in pain, while at 30 days there was a 51% reduction. At 30 days, there was a 43% improvement in flexibility. Nearly 50% of the patients reported being pain free after 1 month.

A more rigorous, double blinded RCT involving 67 subjects with osteoarthritis found similar effects. NEM was given at 500 mg per day for 2 months. Researchers found significant improvements in pain and stiffness as graded by WOMAC (a clinically relevant OA assessment tool) both at 10 days and at 60 days. After 10 days, 54% of subjects in the treatment group had a 20-30% reduction in pain, compared to 24% in the placebo group; at 60 days, 32% vs 12% had 50% reduction in pain. Similar findings were demonstrated for stiffness, with 25% reduction at 10 days, and 53% at 60 days (Ruff 2009b).

Recommended Use: Adult dose is 500 mg or one capsule per day. fast joint care+ contains no artificial colours, flavours, sweeteners or preservatives, corn, dairy, wheat, gluten, soy or yeast. Contraindicated in persons with allergy to egg or egg products. No known adverse effects.

References Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F; National Arthritis Data Workgroup.

Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008 Jan;58(1):26-35.

Ruff KJ, Winkler A, Jackson RW, DeVore DP, Ritz BW. Eggshell membrane in the treatment of pain and stiffness from osteoarthritis of the knee: a randomized, multicenter, double-blind, placebo-controlled clinical study. Clin Rheumatol. 2009 Aug;28(8):907-14.

Ruff KJ, DeVore DP, Leu MD, Robinson MA. Eggshell membrane: a possible new natural therapeutic for joint and connective tissue disorders. Results from two open-label human clinical studies. Clin Interv Aging. 2009;4:235-40.

Theis KA, Helmick CG, Hootman JM. Arthritis burden and impact are greater among U.S. women than men: intervention opportunities

. J Womens Health (Larchmt). 2007 May;16(4):441-53.

Vangsness CT Jr, Spiker W, Erickson J. A review of evidence-based medicine for glucosamine and chondroitin sulfate use in knee osteoarthritis. Arthroscopy. 2009 Jan;25(1):86-94.

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L-Glutamine SAP

Science-based amino acid for gastrointestinal and immune health L-Glutamine is the most abundant amino acid in the human body.(1) Glutamine is metabolized in the small intestine and serves as an important fuel source for intestinal mucosa.(2) Glutamine plays an important protective role in the intestinal tract, and is crucial for patients with increased permeability of the intestinal system, which can be seen in patients with inflammatory bowel diseases including for example Crohn’s disease or ulcerative colitis, as well as in irritable bowel syndrome and allergies.(3, 4) This amino acid plays an important role in nutrient metabolism, the immune system, protein turnover and acid-base balance.(1) With infection, severe burns, cancers and some other pathologies, both intracellular and extracellular concentrations of glutamine are markedly reduced.(1) This leads us to believe that glutamine supplementation may play an important role in the body’s ability to recover from illness. Glutamine has also been studied for use in patients after gastric surgery and may act as a motility-recovery agent after gastrectomy.(5) Patients receiving treatment for cancer often experience malnutrition and cachexia, which may be improved with glutamine supplementation.(6)

Each bottle contains:

ACTIVE INGREDIENTS

L-Glutamine (powder) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300 g Contains no: Preservatives, artificial flavour or colour, sweeteners, wheat, gluten, soy, starch, yeast, citrus, egg or dairy.

L-Glutamine SAP contains 60 servings of 5 g per bottle

ADULT DOSAGE

Take one scoop once or twice daily mixed with juice or water or as directed by your health care practitioner.

INDICATION

L-Glutamine SAP can be use to protect and heal a permeable intestinal tract.

L-Glutamine SAP can help reduce inflammation in the intestinal tract and therefore help treat IBD and IBS.

L-Glutamine SAP may be beneficial to enhance recovery from acute illnesses or infections and severe burns.

L-Glutamine SAP may provide ergogenic benefit to endurance athletes by increasing time to exhaustion.

L-Glutamine SAP could be helpful in preventing postoperative ileus after gastrointestinal surgery.

L-Glutamine SAP may help treat and prevent cachexia and malnutrition in patients undergoing cancer treatment.

SAFETY

L-Glutamine is generally considered safe with the no-observed-adverse-effect-level determined to be 5.0% L-glutamine in the diet, which was around 4000 mg/kg.(7) Scientific Advisory Panel (SAP): adding nutraceutical research to achieve optimum health

PURITY, CLEANLINESS and STABILITY

Third-party testing on L-Glutamine SAP is performed to ensure that the product is free of heavy metals, volatile organic acids and other impurities.

Nutritional Fundamentals for Health • 3405 F.-X.-Tessier, Vaudreuil, QC J7V 5V5 • Tel. 1 866 510 3123 • Fax. 1 866 510 3130 • www.nfh.ca For details, write #117 on Free Info Page, page 96.

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L-Glutamine SAP PRODUCT MONOGRAPH

L-GLUTAMINE AND INFLAMMATION

L-Glutamine administration in recent studies has been shown to enhance heat shock protein (HSP) expression, which may be the key to its mechanism of action with regards to its protective ability.(4) In a study performed on rats which were induced with colitis, animals were administered either 0.75 g/kg/day glutamine or a placebo for 7 days.

After the 7 days, a reduction was observed in bleeding and diarrhea in the treatment group compared to placebo, concomitant with increases in levels of both Hsp25 and Hsp70.(4) Researchers concluded that glutamine is crucial for colonic epithelium to mount a cell-protective, anti-apoptotic and anti-inflammatory response against inflammatory injury.(4)

L-GLUTAMINE AND POSTOPERATIVE ILEUS

One of the most common complications of gastrointestinal surgery is postoperative ileus (POI).(5) In a study conducted on patients after a partial distal gastrectomy for gastric cancer, patients were split into two groups and received either glutamine at 3 g/day or placebo.(5) Results were based on manometric recordings done 12 days after surgery. Motor activity in the duodenum of the glutamine group was significantly greater than that of the control group.(5) Phase-3 motor activity (interdigestive migrating motor contractions) in the glutamine group was rated at 60%, versus 19% in the control group.(5) This study indicates that glutamine can function as a motility-recovery agent after gastrectomy.(5)

L-GLUTAMINE AND ONCOLOGY

For patients with cancer, malnutrition is associated with a poor prognosis, and weight loss can be a very important predictor of mortality.(6) Patients supplementing with glutamine saw benefit, including a reduction in tissue toxicity and improved outcomes, while supporting the efficacy of the chemotherapy treatments.(6) In a study looking at 50 GI cancer patients who had undergone surgery and received total parenteral nutrition (TNP) after surgery, researchers explored the inflammatory modulation effect of glutamine supplementation in one half of the patients.(8) The supplemented group showed a reduction in interleukin-6 (IL-6), serum C-reactive protein, and had higher serum prealbumin levels, as well as better nitrogen balance than the control group.(8) The control group had 4 cases of postoperative infections, while none were reported in the treatment group.(8) Researchers concluded that enriching TPN with glutamine may be beneficial in reducing inflammation and decreasing morbidity associated with infections in postoperative GI cancer patients.(8)

L-GLUTAMINE AND INFLAMMATORY BOWEL DISEASE/IRRITABLE BOWEL SYNDROME

The pathophysiology of irritable bowel syndrome (IBS) is not well understood, but one pathway that may be involved is that of increased intestinal permeability.(3) Researchers performed a controlled study on patients with diarrhea-predominant IBS and assessed their intestinal membrane permeability using the lactulose/mannitol test as well as looking at the glutamine synthetase expression in gut tissue.(3) A subset of 42% of patients had both increased intestinal membrane permeability and decreased glutamine synthetase expression compared to the controls and IBS patients with normal membrane permeability.(3) This result indicates that certain patients with IBS who have increased membrane permeability as well as decreased glutamine synthetase expression may benefit from supplemental glutamine in the diet.

For more information visit: www.nfh.ca

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A study performed in rats looked at the benefit of prophylactic administrations of glutamine for its capability to stop inflammatory damage.(9) Researchers found that administration of glutamine before induction of colitis resulted in decreased indices of inflammation; however, this same benefit was not seen if administered at the same time as the colitis was induced.(9) Further study needs to be performed on human subjects but it may be promising in that glutamine could be useful for patients with colitis in remission to help prevent flare-ups.

L-GLUTAMINE AND ENDURANCE ATHLETES

Endurance athletes often become mildly dehydrated during the course of training and competition. Researchers exploring the effects of L-alanyl-L-glutamine ingestion during performance, measured changes in fluid regulations, immune, inflammatory, as well as oxidative stress, and recovery in athletes who were properly hydrated and during dehydration.(10) Across 4 groups of athletes tested, one group did not rehydrate, group 2 rehydrated using only water, group 3 rehydrated using water and 0.05 g/kg of the supplement, and group 4 rehydrated using water and 0.2 g/kg of the supplement.(10) Subjects then worked at 75% of their VO2 max on a cycle ergometer. Blood samples were obtained immediately following the exercise and after resting for 24 hours.(10) Results demonstrated that athletes in groups 3 and 4 had significantly greater times to exhaustion than those in groups 1 and 2, as well as having lower aldosterone levels and higher plasma sodium levels.(10) Group 4, who received the largest amount of glutamine, demonstrated the greatest improvement.(10) Researchers concluded that the supplementation provided a significant ergogenic benefit to athletes by increasing the time to exhaustion during mild dehydration.(10)

L-GLUTAMINE AND SEVERE BURNS

A clinical study was performed exploring the protective effects of oral supplementation of glutamine in patients with severe burns on intestinal mucosal barrier function.(2) Patients were randomly divided into 2 groups and received either placebo or glutamine granules 0.5 mg/kg orally for 14 days.(2) Results showed that the glutamine group compared to the control group had a lower urinary lactulose/ mannitol ratio, improved wound healing and shorter hospital stays of 46.6 days on average, versus 55.7 days on average in the control group.(2) This study demonstrates that oral glutamine could reduce the amount of intestinal injury and permeability as well as improve wound healing, leading to shortened hospital stays.(2)

SAFETY

L-Glutamine is a safely administered conditional essential amino acid.

Safety studies have demonstrated that L-glutamine can make up 5% of the total dietary intake with no adverse effects noted.(7)

REFERENCES: 1.

Xi, P., Z. Jiang, C. Zheng, Y. Lin, G. Wu. “Regulation of protein metabolism by glutamine: implications for nutrition and health”. Front Biosci 1, no. 16, January 2011: 578–597.

Peng, X., H. Yan, Z. You, P. Wang, S. Wang. “Effects of enteral supplementation with glutamine granules on intestinal mucosal barrier function in severe burned patients”. Burns 30, no. 2, March 2004: 135–139.

3. Zhou, Q., W.W. Souba, C.M. Croce, G.N. Verne. “MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome”. Gut 59, no. 6, June 2010: 775–784.

4. Xue, H., A.J. Sufit, P.E. Wischmeyer. “Glutamine therapy improves outcome of in vitro and in vivo experimental colitis models”. J Parenter Enteral Nutr 35, no. 2, March 2011: 188–197.

5. Mochiki, E., T. Ohno, M. Yanai, Y. Toyomasu, H. Andoh, H. Kuwano. “Effects of glutamine on gastrointestinal motor activity in patients following gastric surgery”. World J Surg 35, no. 4, April 2011: 805–810.

6. Paccagnella, A., I. Morassutti, G. Rosti. “Nutritional intervention for improving treatment tolerance in cancer patients”. Curr Opin Oncol, 2011 May 5. [Epub ahead of print].

7. Wong, A.W., B.A. Magnuson, K. Nakagawa, R.G. Bursey. “Oral subchronic and genotoxicity studies conducted with the amino acid, L-glutamine”. Food Chem Toxicol, 2011 May 27. [Epub ahead of print].

8. Lu, C.Y., Y.L. Shih, L.C. Sun, J.F. Chuang, C.J. Ma, F.M. Chen, D.C. Wu, J.S. Hsieh, J.Y. Wang. “The inflammatory modulation effect of glutamine-enriched total parenteral nutrition in postoperative gastrointestinal cancer patients”. Am Surg 77, no. 1, January 2011: 59-64.

9. Israeli, E., E. Berenshtein, D. Wengrower, L. Aptekar, R. Kohen, G. Zajicek, E. Goldin. “Prophylactic administration of topical glutamine enhances the capability of the rat colon to resist inflammatory damage”. Dig Dis Sci 49, no. 10, October 2004: 1705–1712.

10. Hoffman, J.R., N.A. Ratamess, J. Kang, S.L. Rashti, N. Kelly, A.M. Gonzalez, M. Stec, S. Anderson, B.L. Bailey, L.M. Yamamoto, L.L. Hom, B.R. Kupchak, A.D. Faigenbaum, C.M. Maresh. “Examination of the efficacy of acute L-alanyl-L-glutamine ingestion during hydration stress in endurance exercise”. J Int Soc Sports Nutr 7, no. 1, February 3, 2010: 8–19.

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© NFH Nutritional Fundamentals for Health 2011

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Take control and get back to doing the things you love to do.

Donâ&#x20AC;&#x2122;t let pain stand in the way of living the life you want. Get moving, get going, and get active again, naturally.

Our range of Pain Relief products are specially formulated to target pain effectively and safely. To relieve joint pain and stiffness due to over activity, choose fast joint care+. For clinical strength relief of back pain that works in as little as 2 hours, choose fast back care+. And for relief of pain due to arthritis and range of motion, choose fast arthritis relief+.

Each contain Natural Eggshell Membrane, food for your joints, to not only relieve pain, but also repair damaged joints by providing nutrients that build cartilage, reduce inflammation and increase range of motion, plus additional key ingredients targeted to your type of pain to prevent future flare ups.

| genuinehealth.com *Natural Eggshell Membrane is food for the joints. Safe and 100% natural, Natural Eggshell Membrane is a patented, research-proven ingredient containing naturally occurring ingredients, including glucosamine, chondriotin and hyaluronic acid and Type 1 collagen â&#x20AC;&#x201C; all essential nutrients for proper joint health and flexibility. ** Clinical Intervention in Aging 2009; 4:235-40 For details, write #116 on Free Info Page, page 96.

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