IHP Magazine - September 2013 by IHP Magazine

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Iron & Diabetes

Vitamin E and Cancer

Nigella Sativa

By William R Ware, PhD

By Elizabeth Stavros, ND, Amy Kroeker, ND, and Akbar Khan, MD

By Philip Rouchotas, MSc, ND and Heidi Fritz, MA, ND

Integrated Healthcare

Practitioners

Dr Tris Trethart, MD 30 years of integrative medicine, and counting…

Continuing Education

Mushrooms in Cancer Care: Evidence Review By Christopher Habib, ND and Mark Fontes, ND

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1-2. S heffield IBS Trial Clinical Data: Williams, Plummer et. al. (2008) Clinical trial: a multistrain probiotic preparation significantly reduces symptoms of irritable blowel syndrome in a double-blind placebo-controlled study. Aliment Pharmacol Ther. 29:97-103. 3-4. M adden J.A.J. et al. Effect of probiotics on preventing disruption of the intestinal microflora following antibiotic therapy: A double-blind, placebo-controlled pilot study. Int Immunophar 2005: 5: 1091-1097. Susan F. Plummer et al. Effects of probiotics on the composition of the intestinal microbiota following antibiotic therapy. International Journal of Antimicrobial Agents 2005: 26: 69-74

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AANP 2013: Keystone, Colorado

he IHP team is grateful to the organizing members of the AANP 2013 annual convention. We have had the privilege of attending the AANP convention for six consecutive years now, and the 2013 event in Keystone, Colorado was possibly the most well- hosted to date! IHP was welcomed with open arms, for which we are humbled and grateful. While focusing mostly on a Canadian audience, we were pleasantly surprised to see many American ND’s who were familiar with our work, and even hear reference to IHP articles among speaker presentations! We also want to take a moment to thanks the vendors of the event; they did an excellent job of putting their best foot forward for the convention, showcasing many exciting and important new product launches, improving their delivery of quality information being shared with attending doctors, and creating an enjoyable, social, inviting atmosphere on the tradeshow floor throughout the event. Organizers and vendors go to such amazing lengths to ensure an enjoyable and successful show. We only wish more ND’s from across Canada and the USA would make the effort to attend! It is an excellent opportunity to catch up with colleagues we rarely have the time to see anymore, update the ever- changing landscape of therapeutics our doctors apply daily with patients, and perhaps most importantly, it provides a mid- year refueling of mind, body and soul! A few days in the Colorado mountains works miracles! My batteries feel recharged… time to look ahead to a very busy fall in our industry, and take advantage of all that hard work I did in the garden in the spring!

Sanjiv Jagota Publisher

4 www.ihpmagazine.com l September 2013

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Product Monograph for IHP, August 2013 By Terry Vanderheyden, ND

All is not well in “Big Pharma” Paradise Published in 2002, the Women’s Health Initiative Study (Rossouw et al.) brought to the fore quite soberingly the increased risks for breast cancer, stroke, and myocardial infarct associated with the use of HRT – until then the overwhelming treatment of choice for women with menopausal symptoms. The Fémance Menopause Formula: A synergy of safe, natural, herbal ingredients Dong quai (Angelica sinensis) – William Mitchell, ND (2003) calls dong quai, the premiere women’s tonic from traditional Chinese medicine, an “estrogenic alterative” (alteratives detoxify and aid eliminatory functions). Black cohosh (Actaea racemosa) – In 2010, the Canadian authors of a meta-analysis of clinical trials assessing black cohosh for menopausal symptoms (Shams et al.) confirmed the findings of previous reviews, which “suggested a benefit of black cohosh in reducing the frequency of vasomotor symptoms”. Burdock (Arctium lappa) – Burdock was popular among the Cherokee and Ojibwa Indian tribes, who used it as a blood medicine (purifier) and as a general tonic for women (Moerman 1998). Sage (Salvia officinalis) – Herbalist Matthew Wood (2004) explains that sage is a specific remedy for the transition from fertility to menopause, adding that it restores “that beautiful hormonal glow to the skin that is so feminine”. A clinical trial of sage published in 2011 (Bommer et al.) confirms a highly significant decrease in intensity and frequency of hot flashes. Chaste tree (Vitex agnus castus) – A survey of 280 members of the National Institute of Medical Herbalists (Christie & Walker 1997-8) found that, “An overwhelming majority believed that the use of Vitex for the treatment of female hormone imbalance syndromes was either ‘very effective’ or ‘effective’.” Motherwort (Leonurus cardiaca) – In keeping with its aptly descriptive name, motherwort addresses cardiac manifestations of menopause, such as palpitations and rapid heart rate. In addition, it relieves nervous tension and restlessness. As herbalist David Hoffmann (2003) points out, “It is a useful relaxing tonic for menopausal changes.” Rhodiola (Rhodiola rosea) – Rhodiola boosts brain function and memory, has significant antifatigue effects, and improves sleep. Perhaps its most profound benefit is its mood-elevating property. Dr. Sharon Sageman, Professor of Psychiatry at Columbia University, uses rhodiola as an alternative to prescription antidepressants (Jaret 2005). She has also discovered that rhodiola eases the symptoms associated with menopause and describes the benefits derived from it by a menopausal patient who had gained 10 pounds and lost her sex drive. “I put her on Rhodiola and she quickly felt calmer, her libido returned, and she even lost the weight she’d put on.” Happy Customers A Halifax ND has written to us that, “As a practitioner who sees a large number of peri and menopausal women in my practice, I have seen the dramatic effects it can have on hot flashes, sleep disruption, and mood. My patients and I all love it!” An Ottawa customer says: “I have been telling all my friends about Femance® Menopause’s miraculous effects… I had the most joyful physical transformation, which I had not expected … within a day of taking the tincture”! A Victoria ND adds: “Personally, I have had much success with the tinctures … especially the Femance® Menopause for my female patients with hormonal disturbances.” Another customer relates that she had been experiencing menopausal symptoms for over a year, including hot flashes, heart palpitations, and feelings of anxiety, and that she “found tremendous relief ” from her symptoms.

Terry Vanderheyden, ND (Research Consultant) Since graduating from the CCNM in 1994, Terry Vanderheyden, ND, has practiced in Ontario, specializing in homeopathic, nutritional, and botanical therapies. Terry lives in Barry’s Bay with his wife Laurie and their 7 children.

References: JE Rossouw et al, JAMA 2002; 288(3): 321-333, WA Mitchell, Plant Medicine in Practice: Using the Teachings of John Bastyr, Edinburgh: Churchill-Livingstone; 2003, p. 387. T Shams et al, Altern Ther Health Med, 2010 Jan-Feb; 16(1): 36-44. DE Moerman, Native American Ethnobotany, Cambridge, UK: Timber Press; 1998, p. 85. Matthew Wood, The Practice of Traditional Western Herbalism, Berkeley, CA: North Atlantic Books; 2004, pp. 210-217. S Bommer et al, Adv Ther 2011 Jun; 28(6): 490-500. S Christie and AF Walker, European Journal of Herbal Medicine, 1997-1998; 3(3): 29-45. David Hoffmann, Medical Herbalism: The Science and Practice of Herbal Medicine. Rochester, VT: Healing Arts; 2003, p. 562. Peter Jaret, “Rhodiola Rosea: The Herb That Came in From the Cold,” Natural Solutions Jan 2005; accessed online at http://www.sott. net/article/176940-Rhodiola-Rosea-The-HerbThat-Came-in-From-the-Cold.

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Practitioners Publisher | Sanjiv Jagota (416) 203-7900 ext 6125 Editor-in-Chief | Philip Rouchotas, MSc, ND (416) 203-7900 ext. 6109 Associate Editor | Christopher Habib, ND Art Director | Malcolm Brown Production Manager | Erin Booth (416) 203-7900 ext. 6110 Contributors Christopher Habib, ND, Philip Rouchotas, MSc, ND

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Advertising Information Sanjiv Jagota | Tel: (416) 203-7900 ext 6125 Email: sanjiv@ihpmagazine.com Jeff Yamaguchi | Tel: (416) 203-7900 ext 6122 Email: jeff@gorgmgo.com Jason Cawley | Tel: (416) 203-7900 ext 6134 Email: jason@gorgmgo.com Erin Poredos | Tel: (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

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contents

This Issue: September 2013 • Vol. 6 • No. 4

36 Dr Tris Trethart, MD

Cover Story

Departments

30 years of integrative medicine, and counting…

44 The Pear Tree Clinic Clinic Profile

Leaders in integration – promoters of regulation

The Journal of IHP

Peer-reviewed articles on clinically revelant topics

Coming Next Issue ➜ FODMAPs diet in IBS ➜ Evidence review of hydrotherapy ➜ Games to improve cognition for dementia management

8 www.ihpmagazine.com l September 2013

4 Publisher’s Letter 11 Research News 24 Industry News 31 Calendar 33 Product Profiles 52 Editor’s Letter 56 Peer Review Board 60 Editorial Board 82 Continuing Education: Mushrooms in Cancer Care: Evidence Review

Enhance Your Immune System’s Performance

AOR’s AHCC helps protect the body from foreign invaders and enhances your immunity by stimulating increased production of immune cells

ADVANCED

ORTHOMOLECULAR RESEARCH

AHCC- Product Monograph General Overview The immune system is the body’s system of defense. It is essential for guarding against external threats such as infection, as well as internal problems such as cancer. AHCC is active hexose correlated compound, an oligosaccharide that has been shown to strengthen and optimize the immune system. Clinical Indications AHCC and Cancerous Tumors AHCC was shown effective in several research studies. In one study, AHCC and better nutrition led to a 22% tumor reduction, and 39% tumor stabilization (Matsui Y, 2002). In another study, 6 months of treatment with AHCC (6g/day) led to a partial response in 49.7% of cancer patients and a complete response in 8.8% (Katsuaki Uno, 2000). The combination of AHCC and genistein concentrated polysaccharide (another natural anti-tumor substance) induced apoptosis. Similarly, supplementation of AHCC with an antioxidant extracted from buckwheat, led to the reduction of skin cancer tumors in test rats (Katsuaki Uno, 2000). AHCC in Combination with Chemotherapy Studies using AHCC clearly demonstrated that AHCC safely increases the efficacy of conventional treatments while reducing the frequency of side effects (Hosokawa et al., 1998), (Ikeda et al., 2002). Patients taking AHCC with chemo or radiation saw their tumors shrink and their tumor markers decrease more than patients receiving conventional treatments alone (Ikeda et al., 2002). Furthermore, a weakened immune system is one of the most serious side effects of chemotherapy. AHCC helps to preserve immunity at a time when it is crucial to prevent the spread and growth of abnormal cells. It also reduces the toxicity and the side effects associated with chemotherapy. It alleviates hair loss and bone marrow suppression and prevents the elevation of liver enzymes. Patients taking AHCC reported less nausea and vomiting and AHCC improved their body weight and appetite (Hosokawa et al., 1998). Unfortunately, at present, there are very few proven strategies to reduce the risk of tumor recurrence among survivors. Because of its effect on NK cells, AHCC supplementation may prove useful for those trying to improve their immune function in order to reduce their risk of recurrence. A prospective cohort study found that patients who had undergone resection of a liver tumor had a significantly longer no recurrence period and an increased overall survival rate when they took AHCC (Cowawintaweewat et al., 2006). AHCC and Immunodeficiency Through its influence on the immune system, AHCC may help preserve immunity in those whose defense system is slowly being infiltrated by viruses. Researchers showed that HIV levels could remain suppressed without drugs if the immune system is functioning adequately (Rosenberg et al., 2000). Preliminary trials with AHCC have given encouraging results. AHCC and Infection Infections are caused by the invasion and the multiplication of microorganisms in the body. We carry 500 to 1000 different species of bacteria throughout our body. Adequate immunity is therefore crucial in preventing infection. Several experiments confirmed AHCC’s competence for the control of infections. In one study, mice were administered a 50% lethal dose (LD50) of K. pneumoniae after having restricted food intake for 24 hours prior to and six hours after infection; this simulated local infection and food deprivation that often occurs during trauma or surgical procedures. Survival and mean time to death were increased significantly in the AHCC-treated group; the LD50 was greater in mice receiving AHCC than in mice receiving the excipient alone. Mice receiving AHCC were better able to clear bacteria from their systems than were control animals (Aviles et al., 2006). AHCC and the Liver An excess of toxins can damage the liver. Trials have demonstrated that AHCC protects the liver and improves hepatic function. AHCC was also shown effective for patients with chronic viral hepatitis. One study suggested that AHCC intake could prolong the survival and improve the prognosis of patients with advanced liver cancer and delay the gradual decline of their physiological status (Cowawintaweewat et al., 2006). Compared to the control patients, the AHCC treated-patients having longer survival time had better outcomes in terms of levels of AST and ALT, they had not increased rapidly from their baselines to the follow-up. In addition, the levels of total IL-12 and neopterin were slightly increased in AHCC treated-patients. AHCC and Inflammation It was reported that patients taking AHCC to prevent the recurrence of abnormal growths had significant improvements in rheumatoid arthritis (Kosuna et al., 1999). AHCC was also effective at diminishing inflammation in animal studies. One study found that AHCC administration attenuated inflammation in rats with colitis on a level equal to that of the anti-inflammatory drug sulfasalazine (Daddaoua et al., 2007). It is thought that AHCC reduces inflammation by modulating the immune system and by improving fat metabolism. AHCC and Other Health Conditions Diabetic patients have been shown to respond to AHCC, with reductions of both blood glucose levels and glycated hemoglobin levels. In addition, AHCC appears to be an adaptogen and may help relieve the symptoms/effects of stress (Iwamoto et al., 2009). Supplement Facts SUPPLEMENT FACTS: Serving Size: 1 Capsule AHCC Proprietary Blend – Shiitake mycelium extract

500 mg

Safety The ingredients in this product have been extensively tested in human clinical trials and have been proven safe and effective even in conjunction with some types of chemotherapy. Cautions Do not take if you are pregnant or nursing. Nausea and diarrhea have been known to occur, in which case, discontinue use. Dose and administration Take 1-2 capsules one to three times daily preferably without food or as directed by a qualified health practitioner. Do not take if you are pregnant or nursing. Nausea and diarrhea have been known to occur, in which case, discontinue use. References Ahn GH et al. The Clinical Effectiveness of AHCC Treatment in Cancer Patients with Progressive or Metastasized Cancers: An Observation of Immune Parameters. AHCC Research Association 8th Symposium, Sapporo, Japan, Aug. 2000.

research news Risk of diabetes among patients treated with statins

©iStockphoto.com/stuartbur ©iStockphoto.com/MarsBars

This study examined the risk of diabetes in patients treated with different HMG-CoA reductase inhibitors (statins). This was a population based cohort study with time to event analyses used to estimate the relation between use of particular statins and incident diabetes. All patients were aged 66 years or older and without diabetes when starting treatment on statins (from 1997 to 2010). Patients with established diabetes prior to the start of treatment were excluded. The results showed that compared with pravastatin (the reference drug in all analyses), there was an increased risk of incident diabetes with atorvastatin (HR 1.22, 95% CI 1.15-1.29), rosuvastatin (1.19, 1.10-1.26), and simvastatin (1.10, 1.04-1.17). There was no significantly increased risk among people who received fluvastatin (0.95, 0.81-1.11) or lovastatin (0.99, 0.86-1.14). The absolute

Calcium and vitamin D intake and mortality: results from CaMos

risk for incident diabetes was about 31 and 34 events per 1000 person years for atorvastatin and rosuvastatin respectively. These findings were consistent regardless of whether statins were used for primary or secondary prevention of cardiovascular disease. The authors conclude that compared with pravastatin, treatment with higher potency statins might be associated with an increased risk of new onset diabetes. BMJ. 2013 May 23. PMID: 23704171

©iStockphoto.com/batteriesnotincluded

Effect of fish oil on circulating adiponectin: systematic review and meta-analysis This study performed a systematic review and meta-analysis of randomized, placebo-controlled trials to determine the effect of omega-3 fatty acids (n-3 PUFAs) consumption on circulating adiponectin in humans. Adiponectin is a robust marker for insulin sensitivity and adipocyte function. The data sources included MEDLINE, EMBASE, CABI (CAB abstracts), Cochrane Central Registry of Controlled Trials, ClinicalTrials.gov, SIGLE, and Faculty of 1000. Studies were selected that were RCTs of either fish oil supplementation or isocaloric fish meal feeding that evaluated adiponectin as an outcome. Two investigators independently extracted the data. Of 110 studies, 14 RCTs met inclusion criteria. Fish oil increased adiponectin by 0.37 ug/mL (95%CI 0.07, 0.67). Statistical heterogeneity was evident, unexplained by n-3 PUFA dose or duration, study quality score, study location, or baseline body mass index. Publication bias was assessed using funnel plots and Egger’s test. The authors conclude that in placebo-controlled RCTs, fish oil moderately increases circulating adiponectin, although with unexplained heterogeneity as well as potential publication bias. Thus, these findings provide no evidence for harm and support possible benefits of n-3 PUFA consumption on insulin sensitivity and adipocyte function. J ClinEndocrinolMetab. 2013 May. PMID: 23703724

The Canadian Multicentre Osteoporosis Study (CaMos) cohort is a populationbased longitudinal cohort with a 10-year follow-up (1995-2007). This study examined the association between total calcium and vitamin D intake and mortality and heterogeneity by source of intake. This study included randomly selected communitydwelling men and women. A total of 9033 participants with nonmissing calcium and vitamin D intake data and follow-

up were studied. Total calcium intake (dairy, nondairy food, and supplements) and total vitamin D intake (milk, yogurt, and supplements) were recorded. The outcome variable was all-cause mortality. The results showed 1160 deaths during the 10-year period. For women only, the authors found a possible benefit of higher total calcium intake, with a HR of 0.95 (95% CI, 0.89-1.01) per 500mg increase in daily calcium intake and no evidence of heterogeneity by source. Use of calcium supplements was also associated with reduced mortality, with a HR of 0.78 (95% CI, 0.66-0.92) for users versus nonusers. These associations were not modified by levels of concurrent vitamin D intake. The authors conclude that calcium supplements, up to 1000 mg/d, and increased dietary intake of calcium are associated with reduced risk of mortality in women. J ClincEndocrinolMetab. 2013 May. PMID: 23703722

September 2013 l www.ihpmagazine.com 11

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

research news

Fish oil and neurovascular reactivity to mental stress in humans This study examined whether fish oil would blunt the blood pressure, heart rate (HR), and muscle sympathetic nerve activity (MSNA) responsiveness to mental stress and/or augment limb vasodilation associated with mental stress. Blood pressure, HR, MSNA, forearm vascular conductance (FVC), and calf vascular conductance (CVC) responses were recorded during a 5-min mental stress protocol in 67 nonhypertensive subjects before and after 8 weeks of fish oil (n = 34) or placebo supplementation (n = 33). The results showed that fish oil blunted HR reactivity to mental stress but did not alter blood pressure reactivity to mental stress. Fish oil blunted total MSNA reactivity to mental stress but did not alter MSNA burst frequency and burst incidence reactivity. Finally, fish oil

14 www.ihpmagazine.com l September 2013

significantly blunted CVC reactivity to mental stress but did not alter FVC reactivity. The authors conclude that 8 weeks of fish oil supplementation significantly attenuated both HR and total MSNA reactivity to mental stress and elicited a paradoxical blunting of calf vascular conductance. These findings support and extend the growing evidence that fish oil may have positive health benefits regarding neural cardiovascular control in humans. Am J PhysiolRegulIntegr Comp Physiol. 2013 Apr. PMID: 23408034

ÂŠiStockphoto.com/sandsun

This review article summarizes the results related to the chemopreventive and radioprotective properties of holy basil and emphasizes aspects that warrant future research to establish its activity and utility in cancer prevention

ÂŠiStockphoto.com/bdspn

This review article explored past and current perspectives and future directions on aspirin use. With regards to secondary prevention, where a wide range of patients who have survived a prior occlusive vascular event, as well as during acute myocardial infarction and acute occlusive stroke, aspirin produces statistically significant and clinically important reductions in the risk of subsequent myocardial infarction, stroke, and vascular death. In primary prevention, aspirin reduces risk of a first myocardial infarction, but the data on stroke and vascular deaths remain inconclusive. The average absolute risk of subjects randomized in the primary prevention trials was so low that it is not possible to get reliable estimates of the benefit-to-risk ratio in primary prevention in subjects at moderate risk. Until the results of ongoing trials are available, nobody would disagree that a nonfatal myocardial infarction or stroke is more likely to be disabling than a nonfatal bleed. Thus, the authors conclude that in primary prevention currently, the appropriate and judicious use of aspirin by clinicians based on individual clinical judgments that weigh their absolute benefits against the absolute risks of the drug will avoid premature morbidity and possibly, mortality. Am J Med. 2013 May. PMID: 23499330.

Ocimum sanctum L (holy basil or tulsi) in the prevention and treatment of cancer

and treatment. Ocimum sanctum L. or Ocimumtenuiflorum L, commonly known as holy basil or tulsi is an important medicinal plant in the various traditional and folk systems of medicine in Southeast Asia. Studies have shown it to possess anti-inflammatory, analgesic, antipyretic, antidiabetic, hepatoprotective, hypolipidemic, antistress, and immunomodulatory activities. Preclinical studies have shown that holy basil and some of its phytochemicals eugenol, rosmarinic acid, apigenin, myretenal, luteolin, B-sitosterol, and carnosic acid prevented chemicalinduced skin, liver, oral, and lung cancers and to mediate these effects by increasing the antioxidant activity, altering the gene expressions, inducing apoptosis, and inhibiting angiogenesis and metastasis. The aqueous extract of holy basil and its flavonoids, orintin and vicenin are shown to protect mice against gamma-radiation-induced sickness and mortality and to selectively protect the normal tissues against the tumoricidal effects of radiation. The other important phytochemicals like eugenol, rosmarinic acid, apigenin, and carnosic acid are also shown to prevent radiation-induced DNA damage. Nutr Cancer. 2013. PMID: 23682780

ÂŠiStockphoto.com/sidsnapper

Aspirin in the treatment and prevention of cardiovascular disease

testosterone to DHT (which is the primary molecule that causes hair loss). The SDG from flax lignans in both formulas also decreases excess cholesterol - the building block of testosterone. Based on new research on the rate of metabolism of SDG in flax lignans (8-12 hours on average), the dosage in both products has been revised from once a day to twice a day for optimum results.

Twice the Strength! Double the Power! Bio-Fen® Plus for Men: The mechanism that causes AGA in men follows the same pathway that results in benign prostatic hyperplasia (BPH). For example, the prescription drug finasteride also works by blocking the enzyme 5αreductase and is used as a treatment for both BPH and AGA. For AGA it is marketed under the brand name of Propecia, but the exact same molecule for BPH is sold under the name of Proscar. Hair Grow Technology’s Bio-Fen® product line is continually moving forward! We are introducing our two latest versions; Bio-Fen® Plus for Men and Bio-Fen® Plus for Women. These products have been assigned Natural Product Numbers (NPN’s) by the Natural Health Products Directorate (NHPD) of Health Canada. We recognize that both men and women experience androgenic alopecia (AGA, or male / female pattern baldness) and have made some improvements to the original formulation based on the latest science to address their specific needs. You will notice that we now have additional complementary (Health Canada Approved) health claims on each product.

What causes hereditary hair loss? Each hair grows from a pocket in the skin called the hair follicle. During its growing phase the follicle has a bulb-shaped bottom, the center of which is called the dermal papilla. The paplla is fed by very small blood vessels, which bring it food, oxygen and remove wastes. The papilla is highly sensitive to hormones and chemicals secreted by the body (or ingested as a medicine) which impacts hair growth It is believed that some individuals have a genetic predisposition to a receding hairline (most common in men) or hair (follicle) thinning over larger areas of the scalp (more common in women). These conditions result from hormonal changes caused by an enzyme in the dermal papilla called 5-alpha-reductase. This enzyme breaks down the hormone testosterone into dihyrotestosterone (DHT). Over a period of time, an over abundance of DHT causes the hair follicle to degrade and shortens the active phase of the hair, eventually leading to thinner hair and eventual hair loss.

How does Bio-Fen® PLUS work? We are bringing you two new products with double the number of capsules and triple the number of health claims for men and four times the number of health claims for women, As in the previous formulation, the fenugreek seed extract in both new formulas reduces excess blood lipid levels (hyperlipidemia). Fenugreek contains β-sitosterol, an active plant sterol, which has been shown to inhibit 5-alphareductase activity – the enzyme responsible for converting excess

As before, the saw palmetto extract inhibits the enzyme 5-alpha reductase, and this action slows down the conversion of testosterone to dihydrotestosterone (or DHT) – the overabundance of which causes the miniaturization of hair follicles. This activity of the saw palmetto also helps to relieve the urinary symptoms of mild to moderate BPH for men. The saw palmetto that originally was an extract standardized to 45% free fatty acids, esters, and sterols while the new formula is a 4:1 extract to support the BPH claim. The product still contains these molecules for hair loss, but they are now at proprietary amounts based on our research so that the competition cannot duplicate our formula.

Bio-Fen® Plus for Men will also help to: • Relieve the urologic symptoms associated with mild to moderate benign prostatic hyperplasia - BPH (e.g. weak urine flow, incomplete voiding, frequent daytime and night time urination). • Reduce elevated blood lipid levels / hyperlipidemia.

Bio-Fen® Plus for Women: The women’s formula is almost the same as the men’s formula. The mechanisms and results for the women formula is the same. The only difference is it contains silicon and iron instead of saw palmetto. Silicon has been shown to contribute to hair shaft strength and thus healthy hair growth. It also contains iron which helps prevent iron deficiency. A number of studies have related sub-clinical iron deficiency in women to diffuse hair loss/alopecia. The increased amount of SDG and other revisions to the regulations allow us to make some additional health claims for Bio-Fen® Plus for Women.

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•

Bio-Fen® Plus for Women will also help to: • Reduce elevated blood lipid levels/hyperlipidemia • Prevent iron deficiency. • Metabolize carbohydrates, fats and proteins.

How long must I use Bio-Fen® Plus? Bio-Fen® Plus for Men capsules are usually effective at stopping hair loss within the first two months. However, since healthy hair grows only about 1 cm each month, it may take up to three months before you notice that hair growth is increased or the rate of hair loss is decreased. Anyone experiencing new growth should see it within four months. In some people the original pigmentation may come back. Once you stop completely your hair growth pattern will slowly go back to the point where you started. However, some people may be able to go with a lower maintenance dose.

Why has the recommended dose doubled? Based on new research on the rate of metabolism of SDG in flax lignans (8-12 hours on average), the dosage in both products has been increased to twice a day for optimum results. The flax lignan extract in the original formulation was 100 mg standardized to 20% SDG x 1 capsule per day, which equaled to 20 mg/day of SDG. The new formulations have 200 mg per capsule of flax lignan extract standardized to 50% SDG x 2 caps/day equals 200 mg/day of SDG. As such, one is getting 10 times the amount of SDG per day!.

How safe is Bio-Fen® Plus? The ingredient combination in Bio-Fen® Plus is generally safe for most adults. However, the following cautions are advised: For Men: Consult a health care practitioner prior to use to exclude a diagnosis of prostate cancer, or if you have diabetes. For BPH or elevated blood lipid levels, consult a health care practitioner if symptoms persist or worsen. People sensitive to niacin may experience flushing of the skin that is generally mild and transient. Discontinue use if you experience hypersensitivity to flax, such as an allergy (may occur in rare cases). For Women: Consult a health care practitioner prior to use if you are pregnant or if you have diabetes. Consult a health care practitioner if elevated blood lipid levels persist or worsen. People sensitive to niacin may experience flushing of the skin that is generally mild and transient. Discontinue use if you experience hypersensitivity to flax, such as an allergy (may occur in rare cases). Because of the iron content, some people may experience constipation, diarrhea and/or vomiting. Keep out of the reach of children. There is enough iron in this package to seriously harm a child.

1-866-424-7745 • www.biofen.com

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 distressfor in many men and women (Sinclair 1998). Bio-Fen Plus contains extracts BIO-FEN Men and BIO-FEN for Menaffected andWomen Women 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. inhibitors are responsible for relieving symptoms associated withPlus hereditary AGA. Bio-Fen represents line by for and Bio-Fen for Bio-Fen Bio-Fen representsaaThese lineofofproducts productsapproved approved byHealth HealthCanada Canada forhair hairgrowth growth andrestoration. restoration. Bio-Fen Plus forMen Menand and Bio-FenPlus Plusfor forWomen Womenare areboth bothoral oralnatural naturalhealth health products hair growth women with alopecia (AGA), pattern baldness. contains aacombination ofof One (NHPs) of the which primary causes hairinloss isand a high level ofhereditary the maleandrogenic hormone dihydrotestosterone (DHT) within the Bio-Fen hair follicle (Vierhapper, 2001). products (NHPs) whichsupport support hairof growth inmen men and women with hereditary androgenic alopecia (AGA),ororfemale/male female/male pattern baldness. Bio-Fen contains combination herb extracts and vitamins & minerals that are known to inhibit the enzyme 5!-reductase (5AR), a key pathway implicated in the progression of AGA. herb extracts andwith vitamins & minerals that are known inhibit the enzymeof 5 androgen -reductase (5AR), a keyto pathway in the progression of AGA. catalyzes the enzymatic For people AGA, their follicles have atogreater number receptors whichimplicated DHT attaches. 5-α-reductase conversion of testosterone to dihydrotestosterone, which binds to the receptor five-fold more avidly than the parent compound (Sinclair 1998). AGA AGAPathophysiology Pathophysiology

One Oneofofthe theprimary primarycauses causesofofhair hairloss lossisisaahigh highlevel levelofofthe themale malehormone, hormone,dihydrotestosterone dihydrotestosterone(DHT) (DHT)within withinthe thehair hairfollicle follicle(Hoffmann (Hoffmann2002). 2002).DHT DHTisisproduced producedfrom from testosterone ininthe the over Saw palmetto (Serenoa repens) testosterone thetestes testes(males), (males), theadrenal adrenalglands, glands,and andthe thefollicle. follicle.After Afteraaperiod periodofoftime, time,an anVitamins overabundance abundanceofofDHT DHTcauses causesthe thehair hairfollicle follicletotodegrade degradeand andshortens shortensthe theactive active phase ofofthe eventually totothinning hair and hair There isisaafamilial for ofofthe follicle ininthe phase thehair, hair,(lipophillic) eventuallyleading leading thinning hairbeen andeventual eventual hair loss. Thereinhibitor familialtendency tendency forstepwise stepwise miniaturization thehair hair follicleand and anincrease increase theratio ratio In a Polish study ofminiaturization 46 women who had symptoms of an diffuse alopecia, calcium Standardized Serenoa extract has found to beloss. a potent ofoftelogen (resting totoanagen (growth hairs, isispromoted by effects with aa four to telogen (restingphase) phase) anagen (growthphase) phase)DHT. hairs,which which promoteddose bysystemic systemic andlocal local effectsof ofandrogens. androgens. Althou gheveryone everyone produces DHT, only thosemg with pantothenate was orally Although administered twiceproduces a day inDHT, dosesonly of those 100 for of 5α-reductase, resulting in decreased tissue An open-label, responseand higher number ofofandrogen inintheir hair binding sites and sensitivity experience hair loss 2002). 5AR responsible for higher number androgen receptors their hair follicles, binding sitesfor foraDHT, DHT, andgreater greaterandrogen androgen sensitivity experience hairinjected loss(Prager (Prager 2002). 5AR responsible forthe the five months, and vitamin B6 was every day for 20isisto 30 days and repeated study was conducted onreceptors 42 healthy males tofollicles, determine the effect of combination conversion ofoftestosterone totodihydrotestosterone, which binds totothe same receptor, but five-fold greater affinity. 2002) conversion testosterone dihydrotestosterone, binds the sameandrogen androgen butwith with five-fold greater(Brzezińska-Wcisło affinity.(Hoffmann (Hoffmann2002, 2002,Trueb Trueb after six months 2001). It was2002) determined that vitamin again of carotenoid astaxanthin and saw palmettowhich berry lipid extract on DHT receptor, and

B6 administered parenterally for a few weeks induces improvement in the hair testosterone levels (Angwafor 2008). The men were divided into two groups: Flax Flax condition for in subset women andFlax reduces hairare loss. one group received 800 mg/day of balancing the combination supplement and the other Flax lignans inhibit the 5AR, formation ofofthe that loss (Evans 1995). lignans converted Flax lignans inhibit theenzyme enzyme 5AR,thus thus balancing formation themale malehormones hormones thatare areresponsible responsible forahair hair lossof (Evans 1995). Flax lignans are convertedby bythe thebody bodytoto group received 2000 mg/day ofestrogen the supplement for 14 days. ANOVA-RM enterolactones, which compete with and for binding, and enterolactones, which compete with estrogen andtestosterone testosterone forreceptor receptor binding,showed andincrease increasesex sexhormone hormonebinding bindingglobulin globulin(SHBG), (SHBG),resulting resultingininlower lowerlevels levelsofoffree free(ie (ieactive) active) estrogen and Flaxseed has serum ofof17-beta-estradiol and significant within-group increases in shown serum testeosterone significant estrogen andtestosterone. testosterone. Flaxseed hasbeen been showntototal toreduce reduce serumlevels levelsand 17-beta-estradiol andestrone estronesulfate sulfate(Hutchins (Hutchins2001), 2001),and andresults resultsininaashift shiftininestrogen estrogenmetabolism metabolismtoto Medicinal Ingredients Dose Per Capsule favor the active estrogens (Brooks decreases in serum DHT baseline in 2004). both favor theless lessbiologically biologically activefrom estrogens (Brooks 2004).dose groups (P=0.05). There was no significant difference between dose groups with regard to the increase of

Fenugreek (Trigonella foenum graecum)

Fenugreek Fenugreek 260 mg testeosterone or the decrease of DHT; therefore both doses were effective (Angwafor seed extract 4:1 such as "-sitosterol have been shown to block DHT Fenugreek has been used traditionally as an oral and topical treatment for hair loss. Plant sterols contained in fenugreek Fenugreek 2008). has been used traditionally as an oral and topical treatment for hair loss. Plant sterols contained in fenugreek such as -sitosterol have been shown to block DHT receptor receptorsites sites(Prager (Prager2002, 2002,see seebelow). below).

Saw palmetto berry extract containing

160 mg

Another study tested liposterolic extract of Serenoa repens (LSESr) and beta45% free fatty acids Saw Palmetto (men’s product) Saw Palmetto (men’s product) sitosterol inextract the treatment ofinhibitor males (23-64 of age) with mild to moderate AGA. Saw palmetto isisaapotent ofof5!-reductase, resulting inindecreased tissue DHT Saw palmetto extract potent inhibitor 5 years -reductase, resulting decreased tissue DHT(Prager (Prager2002). 2002).In Inaapilot pilotstudy studyof of26 26men menwith withmild mildtotomoderate moderateAGA, AGA,treatment treatmentwith with Flax lignans, standardized toblinded 20% assessors Six of 10 (60%) subjects were rated extract asextract improved atand thebeta-sitosterol final visit, thus establishing aacombination ofoflipophilic saw palmetto 200mg 50mg improved by asasscored combination lipophilic saw palmetto 200mg and beta-sitosterol 50mg improvedsymptoms symptoms byup uptoto60%, 60%, scoredby by blinded assessors(Prager (Prager 2002). InInaameta meta 100 2002). mg secoisolariciresinol diglucoside analysis by group, has found totobe 2002). the effectiveness of 5α-reductase inhibitors against AGA (Prager 2002). as Chronic analysis bythe theCochrane Cochrane group,saw sawpalmetto palmetto hasalso alsobeen been found beeffective effective asaatreatment treatmentfor forsymptoms symptomsofofBPH BPH(Wilt (Wilt 2002). (SDG) inflammation of the hair follicle is considered to be a contributing factor for AGA. A

D-calcium pantothenate (Vitamin B5) 10.40 mg Silica (women’s product) Silica (women’s product) study by Chittur et al sought to determine whether blockade of inflammation using Silica isisaatrace mineral that has been found totoincrease hydroxyproline concentration ininconnective tissue (Barel 2005). InInaarandomized, double blind, placebo Silica trace mineral that has been found increase hydroxyproline concentration connective tissue (Barel 2005). randomized, double blind, placebocontrolled controlledstudy, study,50 50 LSESr and two anti-inflammatory agents (carnitine and thioctic acid) could alter Niacinamide (Vitamin B3) 10.25 mg visualanalog women with skin with asasorthosilicic acid (OSA) daily women withdamaged damaged skinwere weretreated treatedorally orally with10mg 10mgsilica silica orthosilicic acid (OSA) dailyfor for20 20weeks. weeks.The Thetreatment treatmentgroup groupreported reportedaasignificant significantdecrease decreaseininvisual analog the expression of molecular markers of inflammation (Chittur 2009). It was found scale brittle hair found that blind,placebo placebocontrolled controlledtrial trialconducted conductedinin50 50women womenwith that10mg 10mgsilica silicaasasOSA OSA scaleratings ratingsofofhair hairbrittleness brittleness(Barel (Barel2005). 2005).AAsecond secondrandomized, randomized,double doubleblind, Pyridoxine HCl (Vitamin B6) with brittle hair found 2 mg thatmonths the combination suppressedhair lipopolysaccharide-activated gene (thickness) expression(Wickett of for significantly elasticity, for99months significantlyimproved improvedhair elasticity,breakage, breakage,and anddiameter diameter(thickness) (Wickett2007). 2007). chemokines associated with pathways involved in inflammation and apoptosis.

Riboflavin (Vitamin B2)

1.58 mg

Folic acid

0.095 mg

The study concluded thatcell 5-alpha reductase inhibitors in optimal combination with BBvitamins are growth and metabolism. vitamins aresupport supporthealthy healthy cell growthand anddivision, division, andfacilitate facilitate optimalhormone hormone metabolism. blockade of inflammatory processes could represent a new two-pronged approach Medicinal ingredients Medicinal ingredients percapsule capsuleininboth boththe themen’s men’sand andwomen’s: women’s: in the treatment of per AGA.

Fenugreek 260 mg Fenugreek(Trigonella (Trigonellafoenum foenumgraecum) graecum)seed seedextract extract4:1 4:1.................................................... ....................................................260 mg Biotin 400 mcg equiv (dry equiv1040mg) 1040mg) Fenugreek(dry Seeds Flax lignans, standardized toto50% SDG ............................................................................... 100 mg Flax lignans, standardized 50% SDG ...............................................................................100 mg Non-Medicinal Ingredients Fenugreek seeds contain 5% to 30% protein, steroid saponins, sterols, flavonoids d-calcium 10.4 mg d-calciumpantothenate pantothenate(Vitamin (VitaminB5) B5) .................................................................................. ..................................................................................10.4 mg and alkaloids (notably trigonelline and choline). Steroid saponins bind and10.3 mg Niacinamide Niacinamide(Vitamin (VitaminB3) B3) ................................................................................................... ...................................................................................................10.3 mg Inert microcrystalline cellulose and vegetable-based magnesium eliminate extra cholesterol and hormones in the body; DHT is made from Pyridoxine 2.0 mg PyridoxineHCl HCl(Vitamin (VitaminB6) B6)............................................................................................... ...............................................................................................2.0 mgstearate in a veggie-based capsule testosterone, which in turn is made from cholesterol. Therefore, when excess1.6 mg Riboflavin (Vitamin B2) ....................................................................................................... (Vitamin B2)is .......................................................................................................1.6 mg Riboflavin is eliminated, less DHT can be made (Stark 1993). In a study of 2095 mcg cholesterol Folic acid Folic acid .............................................................................................................................. ..............................................................................................................................95 mcg Biotin .................................................................................................................................... Recommended adult dose: One capsule per day adults who consumed 12.5g and 18.0g of germinated fenugreek seed powder for250 mcg Biotin ....................................................................................................................................250 mcg

one month, higher levels of consumption resulted in a significant reduction in total

Men’s also Men’s alsohas: has: cholesterol and low-density lipoprotein (LDL) levels (Sowmya 1999). Saw 125 mg Sawpalmetto palmettoberry berryextract extract4:1 4:1............................................................................................. .............................................................................................125 mg (dry equiv. 500 mg) (dry Flax lignans equiv. 500 mg)

Flax reduces the amount of DHT produced by reducing cholesterol levels in the Women’s Women’salso alsohas: has: body.(silicon A meta-analysis of 28 studies between 1990 and 2008 showed that flaxseed40 mg Silicon dioxide) Silicon (silicon dioxide)........................................................................................................ ........................................................................................................40 mg significantly reduces circulating total and LDL-cholesterol concentrations (Pan20 mg Iron (ferric ................................................................................................................ Iron (ferriccitrate) citrate) ................................................................................................................20 mg 2009). Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L

Recommended use: one capsules per Bio-Fen® Plus Recommended use:0.00 onecapsule capsuletwice twice daily (60 capsules perbottle). bottle). Bio-Fen® Pluscapsules capsulesare areusually usuallyeffective effective (95% CI: -0.20, mmol/L) anddaily 0.08(60 mmol/L (95% CI: -0.16, 0.00 mmol/L), atatstopping first Anyone experiencing new should stoppinghair hairloss losswithin withinthe the firsttwo twomonths. months. Anyonewith experiencing newgrowth growth should seeititwithin withinfour fourmonths. months. respectively. Significant reductions were observed whole flaxseed (-0.21 and see Once Bio-Fen isisstopped, the growth pattern will return totoits point, Once Bio-Fen stopped, thehair hairand growth pattern willslowly slowly return itsoriginal original point,however howeversome somepeople peoplemay may -0.16 mmol/L, respectively) lignan (-0.28 and -0.16 mmol/L, respectively) be with aalower beable abletotocontinue continue with lowermaintenance maintenancedose. dose. supplements (Pan 2009). Bio-Fen Bio-Fenhas hasbeen beenapproved approvedby byHealth HealthCanada Canadaand andhas hasreceived receivedaaunique uniqueNPN NPNnumber. number.InInaddition additiontotobeing beingapproved approved for forhair hairgrowth growthapplications, applications,Bio-Fen Bio-Fenhas hasbeen beenapproved approvedfor foradditional additionalhealth healthbenefits. benefits. Angwafor F III, Anderson ML. An open label, dose the effect of a dietary supplement dihydrotestosterone, testosterone and estradiol levels in healthy males. J Contraindications: The ingredient combination in response Bio-Fenstudy Plus to fordetermine Men/Women is generally safe for most on adults. Int Socshould Sportsnot Nutr Bio-Fen be2008;5:12. usedingredient by patientscombination with diabetes, or knownPlus hypersensitivity to any ingredients. Contraindications: The in Bio-Fen for Men/Women is generally safe for most adults. Bio-Fen should not be used by patients withB6 diabetes, or known hypersensitivity to any ingredients. Brzezińska-Wcisło L. Evaluation of vitamin and calcium pantothenate effectiveness on hair growth from clinical and trichographic aspects for treatment of diffuse alopecia in women. Wiad References Lek 2001;54:11-8. Brooks JD, et al. Am J Clin Nutr. 2004 Feb;79(2):318-25. References 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 Evans BA, 1995 Brooks JD,etetal.al. Am Nov;147(2):295-302. J Clin Complement Alternat Med Nutr. 2009. 2004 Feb;79(2):318-25. Hoffmann Exp Dermatol. 2002 Jul;27(5):373-82. Evans BA,R.etClin al. 1995 Nov;147(2):295-302. 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. Hutchins AM,et al. Nutr Cancer. Hoffmann R. Clin Exp Dermatol.2001;39(1):58-65. 2002 Jul;27(5):373-82. Prager N, et al. 2002 Apr;8(2):143-52. 2001;39(1):58-65. Hutchins AM,et al.K, Nutr Cancer. Prager N, Bickett 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 Trüeb RM. Gerontol. 2002 Aug-Sep;37(8-9):981-90. Prager N, etExp al.androgenetic 2002 Apr;8(2):143-52. treatment of alopecia. J Altern Complement Med 2002;8:143-52. Wickett RR, Exp et alGerontol. Arch Dermatol Res. 2007 Dec;299(10):499-505. Trüeb RM. 2002 Aug-Sep;37(8-9):981-90. Serenoa repens monograph. Alternative Medicine Review 1998;3:227-9. Wilt T et al. Cochrane Database Syst Rev. 2002;(3):CD001423. Wickett RR, et al Arch Dermatol Res. 2007 Dec;299(10):499-505. Wilt T et al. Database Syst Rev. 2002;(3):CD001423. Sinclair R. Cochrane 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.

research news ©iStockphoto.com/RedHelga

Impact of marijuana use on glucose, insulin, and insulin resistance

Vitamin C kills mycobacterium tuberculosis

©iStockphoto.com/CapturedNuance

This study examined the possible benefits of adding vitamin C to anti-tuberculosis regimen and suggests the development of drugs that generate high oxidative bursts. Drugs that kill tuberculosis more quickly could shorten chemotherapy significantly. In Escherichia coli, a common mechanism of cell death by bactericidal antibiotics involves the generation of highly reactive hydroxyl radicals via the Fenton reaction. The Fenton reaction occurs because several metals have special oxygen transfer properties which improve the use of hydrogen peroxide and some metals have strong catalytic power to generate highly reactive hydroxyl radicals. Iron catalyzed

hydrogen peroxide is called Fenton’s reaction. In this article, it is shown that vitamin C, a compound known to drive the Fenton reaction, sterilizes cultures of drug-susceptible and drug-resistant Mycobacterium tuberculosis, the causative agent of tuberculosis. While M. tuberculosis is highly susceptible to killing by vitamin C, other Grampositive and Gram-negative pathogens are not. The bactericidal activity of vitamin C against M. tuberculosis is dependent on high ferrous ion levels and reactive oxygen species production and causes a pleiotropic effect affecting several biological processes. The authors conclude vitamin C could be beneficial to anti-tuberculosis regimens. Nat Commun 2013. PMID: 23695675

Mediterranean diet improves cognition: PREDIMED-NAVARRA study

©iStockphoto.com/pacopole

This study examined the effect of the Mediterranean diet (MedDiet) on cognition. Previous observational studies reported beneficial effects but results were inconsistent. This study compared MedDiets with lowfat control diets. 552 participants at high vascular risk (44.6% men in their seventies) were enrolled in a multicenter, randomized, primary prevention trial (PREDIMED), after a nutritional intervention comparing two MedDiets (supplemented with either extra-virgin olive oil or mixed nuts) versus a low-fat control diet. Global cognitive performance was examined by Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT) after 6.5 years of nutritional intervention. The results showed that after adjustments for sex, age, education, Apolipoprotein E genotype, family history of cognitive impairment/demntia, smoking, physical activity, body mass index, hypertension, dyslipidemia, diabetes, alcohol and total energy intake, participants allocated to the MedDiet and olive oil showed higher mean MMSE and CDT scores with significant differences versus control. Similar positive results were found with the MedDiet and nuts intervention outperforming the low-fat control diet. The authors conclude that intervention with MedDiets enhanced with either olive oil or nuts appears to improve cognition compared with low-fat diets. J NeurolNeurosurg Psychiatry. 2013 May. PMID: 23670794.

This study examined the relation between marijuana use and markers of diabetes mellitus. Prior to this study, there was limited data regarding the relationship between cannabinoids and metabolic processes. Epidemiologic studies have found lower prevalence rates of obesity and diabetes mellitus in marijuana users. The authors included 4657 adult men and women from the National Health and Nutrition Examination Survey from 2005 to 2010. Marijuana use was assessed by self-report

in a private room. Fasting insulin and glucose were measured by blood samples after a nine hour fast. Insulin resistance was evaluated using a homeostasis model assessment of insulin resistance (HOMA-IR). The results showed that of the participants in the study sample, 579 were current marijuana users and 1975 were past users. In multivariable adjusted models, current marijuana use was associated with 16% lower fasting insulin levels (95% CI, -26, -6) and 17% lower HOMA-IR (95% CI, 27, -6). The authors found significant associations between marijuana use and smaller waist circumferences. Among current users, they found no significant dose-response. The authors conclude that marijuana use was associated with lower levels of fasting insulin and HOMA-IR and smaller waist circumference. Am J Med. 2013 May. PMID: 23684393

September 2013 l www.ihpmagazine.com 17

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.

Consumption of walnuts affects cholesterol

This study investigated the efficacy of different dosages of vitamin D in supporting 25-hydroxyvitamin D concentrations in infants. The study was double-blinded and randomized. It included 132 one-month-old healthy, term, breastfed infants. Infants were followed up for 11 months and 74% completed the study. Participants were randomly assigned to receive oral cholecalciferol (vitamin D3) supplements of 400 IU/d (n=39), 800 IU/d (n=39), 1200 IU/d (n=38), or 1600 IU/d (n=16). The results showed that at 3 months, 55% of infants in the 400 IU/d group achieved concentrations of 75 nmol/L or greater vs. 81% in the 800 IU/d group, 92% in the 1200 IU/d group, and 100% in the 1600 IU/d group. This was sustained in 97.5% of infants at 12 months in all groups. The 1600 IU/d dosage was discontinued prematurely because of elevated plasma 25(OH)D concentrations. All dosages established concentrations of 50 nmol/L or grater in 97% of infants at the months end and sustained it in 98% to 12 months. The authors conclude that for healthy, term, breastfed infants, only 1600 IU/d increased 25(OH)D to 75 nmol/L or greater in 97.5% of infants at 3 months but that this dose is associated with hypercalcemia. JAMA.2013 May. PMID: 23632722

This study investigated the impact of walnut and walnut component consumption on cardiovascular risk. A randomized, 4-period, crossover trial was conducted in 15 healthy overweight and obese adults with moderate hypercholesterolemia. This study had participants consume whole

This study discusses cassia cinnamon as a source of coumarin in cinnamonflavored foods and supplements in the United States. Coumarin as an additive or constituent of tonka beans or tonka extracts is banned in the United States due to its potentially adverse side effects. However, coumarin in food from other natural ingredients is not regulated. “True Cinnamon” refers to the dried inner bark of Cinnamom verum. Other cinnamon species such as C. cassia, C. loureiroi, and C. burmannii, are also sold in the U.S. as cinnamon. In this study, coumarin and other marker compounds were analyzed in authenticated cinnamon bark samples as well as locally bought cinnamon samples, cinnamon-flavored foods, and cinnamon-based food supplements using a validated method.

20 www.ihpmagazine.com l September 2013

The results showed that C. verum bark contained only traces of coumarin, whereas barks from all three cassia species contained substantial amounts of coumarin. These cinnamon species could be potential sources of coumarin and thus could have potential safety implications for consumers. Their chemical profiles indicated that the cinnamon samples and the cinnamon in food supplements and flavored foods were probably Indonesian cassia, C. burmannii. J Agric Food Chem. 2013 May. PMID: 23627682

walnuts (85g), separated nut skins (5.6g), de-fatted nutmeat (34g), and nut oil (51g). Multiple factors were then assessed, including postprandial lipemia, endothelial function, and oxidative stress. Cholesterol efflux was assessed in the whole walnut treatment only. The results showed that there was a treatment and time point interaction for triglycerides and increased postprandial concentrations were observed for the oil and whole walnut treatments. Walnut skins decreased the reactive hyperemia index (RHI) compared with baseline, such that a difference persisted between the skin and oil treatments. The Framingham RHI was maintained with the oil treatment compared with the skins and whole nut. There was a treatment effect for the ferric reducing antioxidant potential (FRAP) and mean FRAP was greater with the oil and skin treatments compared with the nutmeat. Cholesterol efflux increased by 3.3% following whole walnut consumption. The authors conclude that walnut oil favorably affected endothelial function and whole walnuts increased cholesterol efflux. J Nutr. 2013 Jun. PMID: 23616506

©iStockphoto.com/StudioThreeDots

Cassia cinnamon as a source of coumarin in cinnamon-flavored food and supplements

©iStockphoto.com/Floortje

Different dosages of oral vitamin D supplementation on vitamin D status in infants

©iStockphoto.com/AsherDB

research news

Full-Spectrum Longevity Support RevitalAge™ Ultra delivers longevity benefits with sustained-release coenzyme Q10, pure resveratrol, pterostilbene to offer enhanced antioxidant and mitochondrial support. RevitalAge™ Ultra Supports Youthful Gene Expression

Mitochondrial Renewal

Healthy Aging

Resveratrol supports longevity by enhancing an epigenetic enzyme, SIRT1. It also works in concert with alpha lipoic acid and acetyl-l-carnitine to cooperatively support the synthesis of new mitochondria by promoting healthy activity of another enzyme known as AMP kinase (AMPK), a cellular longevity signal that directs a genetic program of mitochondrial renewal. Sustained-release CoQ10 provides 24-hour antioxidant protection with complementary support for mitochondrial bioenergetics. Pterostilbene supports healthy activation of PPARα, a genomic receptor involved in cardiometabolic health. †

Under license from

Inc.

This product contains resVida®. resVida® is a registered trademark of DSM Nutritional Products, Inc.

Your Trusted Source for science-based, hypo-allergenic nutritional supplements. 866-856-9954 | Quebec Practitioners: 800-361-0324 | purecaps.ca The information contained herein is for informational purposes only and does not establish a doctor-patient relationship. Please be sure to consult your physician before taking this or any other product. Consult your physician for any health problems.

RevitalAge Ultra ™

What Is It? RevitalAge™ Ultra is a scientifically researched combination of acetyl-l-carnitine (ALC) and alpha lipoic acid (ALA) offered with PhytoLongevity, a polyphenol blend that supports inflammatory balance, cardiometabolic health and cognitive performance. The formula also includes a unique blend of sustained-release CoQ10, pure resVida® resveratrol and pterostilbene to promote healthy aging through maintaining youthful gene expression, mitochondrial function, cellular energy production and antioxidant protection.

Uses For RevitalAge™ Ultra Cellular Health and Longevity: Over a decade of research has associated healthy mitochondrial function with longevity. Preclinical research on aging conducted by an award-winning team of scientists at UC Berkley, including Dr. Bruce Ames, has revealed a combination of acetyl-l-carnitine, alpha lipoic acid and biotin can promote longevity. Dietary polyphenols from fruits and vegetables provide cellular protection by maintaining youthful patterns of gene expression in the heart, blood vessels and brain. Sustained-release CoQ10 provides 24-hour mitochondrial support. Pure resVida® resveratrol and pterostilbene target cellular pathways and genes involved in the aging process.

Special Features Patented Longevity Combination: • Patented, scientifically researched combination of acetyl-l-carnitine (ALC), alpha lipoic acid (ALA) and biotin, used under license from Juvenon, Inc. • Supports healthy gene expression and increases mitochondrial number for enhanced cellular energy production • In preclinical studies, this patented ratio of ALC and ALA has enabled elderly laboratory animals to function at a level characteristic of much younger animals • Clinical research indicates that the combination supports total plasma antioxidant capacity, cardiovascular health and psychological well-being PhytoLongevity: A Spectrum of Natural Polyphenols for Healthy Aging: • Polyphenols are active constituents of cardio- and neuroprotective fruits and vegetables; this proprietary blend contains cranberry, wild blueberry, strawberry and spinach leaf extracts • The unique ratio of blueberry and cranberry support healthy inflammatory balance by maintaining healthy activity of nuclear factor kappa-B (NFκB), a regulator of gene expression • Cranberry, strawberry and spinach polyphenols maintain healthy activity of prolyl endopeptidase (PEP), an enzyme that regulates neurotransmission; healthy PEP activity supports memory and cognition

MicroActive® sustained-release CoQ10 • Water-soluble • 24-hour sustained release with low inter-subject variability • Clinical research shows 300% greater peak plasma concentrations compared to standard CoQ10 resVida®: pure, clinically researched resveratrol • Pure trans-resveratrol with clinically proven bioavailability • Potent antioxidant that protects mitochondria from free radicals that contribute to cellular aging • Supports the expression of longevity genes in the cardiovascular system and brain associated with life span in preclinical studies pterostilbene: pure, methylated resveratrol • Pure, clinically researched pterostilbene, the methylated analog of resveratrol • Promotes cardiometabolic health by supporting healthy PPAR-alpha receptor activity • Provides synergistic antioxidant support when combined with resveratrol

What Is The Source? Acetyl-l-carnitine HCl†, alpha lipoic acid (thioctic acid), biotin, resVida® resveratrol and pterostilbene are synthetic. MicroActive® CoQ10-cyclodextrin complex containscoenzyme Q10 obtained naturally from fermentation and potato starch. PhytoLongevity proprietary blend is sourced from cranberry extract, wild blueberry extract, Orléans strawberry extract and spinach extract. RevitalAge™ Ultra three vegetable capsules contain

v 00

biotin† ...........................................................................................................................................2 mg acetyl-l-carnitine HCl† ......................................................................................................1,000 mg alpha lipoic acid (thioctic acid)† ...................................................................................... 400 mg resVida® resveratrol (as trans-resveratrol) ........................................................................30 mg CoQ10 (from MicroActive® Q10-cyclodextrin complex) .......................................................30 mg pterostilbene ..............................................................................................................................5 mg PhytoLongevity proprietary blend.......................................................................................200 mg providing cranberry (Vaccinium macrocarpon) extract (fruit), wild blueberry (Vaccinium angustifolium) extract (fruit), Orléans strawberry (Fragaria vesca var Orléans) extract (fruit) and spinach (Spinacia oleracea) extract (leaf) other ingredients: potato starch, maltodextrin

3 capsules daily, with meals. †Under

license from

Inc.

This product contains resVida®. resVida® is a registered trademark of DSM Nutritional Products, Inc.

866.856.9954 | Purecaps.ca The information contained herein is for informational purposes only and does not establish a doctor-patient relationship. Please be sure to consult your physician before taking this or any other product. Consult your physician for any health problems.

research news ©iStockphoto.com/FrancoDeriu

Effects of ginger on airway smooth muscle relaxation and calcium regulation

©iStockphoto.com/Kenishirotie

This study examined four purified active constituents of ginger and their ability to provide airway smooth muscle relaxation. Asthma is characterized by airway hyperresponsiveness and inflammation. Many patients report using alternative therapies to self-treat asthma symptoms as adjuncts to shortacting and long acting B-agonists and inhaled corticosteroids. As many as 40% of patients with asthma use herbal therapies to manage their asthma symptoms, but without proven efficacy or known mechanisms of action. In this study, four purified constituents of ginger were tested for airway smooth muscle relaxant properties in both guinea pig and human tracheas. The results showed that [6]-gingerol, [8]-gingerol, and [6]-shogaol induced rapid relaxation of precontracted airway

Interactions of dietary tomato powder and soy germ on prostate carcinogenesis

smooth muscle (100-300μM), whereas [10]-gingerol failed to induce relaxation. In human airway smooth muscle cells, exposure to the same constituents blunted subsequent calcium responses to bradykinin (10μM) and S-(-)-Bay K 8644 (10μM).The authors conclude that these data show that ginger and its isolated active components relax airway smooth muscle, and [8]-gingerol attenuates airway hyperresponsiveness, in part by altering calcium regulation. These purified compounds may provide a therapeutic option alone or in combination with accepted therapeutics in airway diseases. Am J Respir Cell Mol Biol. 2013 Feb. PMID: 23065130

Age and chronic cigarette smoking effects on neurocognition in alcohol-dependent individuals

©iStockphoto.com/Stepan Popov

This study examined the impact of increasing age and chronic cigarette smoking on neurocognition in those seeking treatment for alcohol use disorders. Cross-sectional performances of never-smoking healthy comparison participants and 1-month-abstinent, treatmentseeking, never-smoking, former-smoking, and actively smoking alcohol-dependent individuals were compared on a comprehensive neurocognitive battery. Domains of functioning evaluated were cognitive efficiency, executive functions, fine motor skills, general intelligence, learning and memory, processing speed, visuospatial functions and working memory. The results showed that those who were smokingabstinent had steeper age-related effects than never-smoking individuals on the domains of visuospatial learning, auditory-verbal memory, cognitive efficiency, executive functions, processing speed, and fine motor skills. In pairwise comparisons, former-smokers and abstinent smokers performed more poorly than never smokers. The authors conclude that the combination of active smoking and alcohol dependence in this cohort was associated with greater than normal agerelated effects in multiple domains. In general, a low level of clinically significant impairment was observed in the alcohol-dependent participants. The findings from this study and in conjunction with other research strongly support smoking cessation interventions for those seeking treatment for alcohol and substance use disorders. Alcohol ClinExp Res. 2013 May. PMID: 23682867

This study examined the interactions between bioactive rich food components within a complex human diet for the inhibition of prostate carcinogenesis. In particular, tomato and soy products have each shown antiprostate carcinogenesis in laboratory studies. This study investigated the efficacy of dietary tomato and soy germ, alone and in combination, for the inhibition of prostate carcinogenesis in the transgenic adenocarcinoma of

mouse prostate (TRAMP) model. The methods were that at 4 weeks of age, male C57BL/6 x FVB TRAMP mice (n = 119) were randomized to consume: AIN-93G control, 10% whole tomato powder (TP), 2% soy germ powder (SG) or 10% tomato powder with 2% soy germ powder (TP+SG) for 14 weeks. The results showed that 100% of mice fed the control diet had prostate carcinogenesis, whereas the incidence was significantly lower in mice consuming TP (61%, p<0.001), SG (66%, p<0.001) and TP+SG (45%, p<0.001). The protection offered by the combination of TP and SG was not synergistic, but was the most effective intervention. TP, SG, and TP+SG all increased the apoptotic index and modestly reduced the proliferative index in the prostate epithelium of TRAMP mice exhibiting primarily prostatic intraepithelial neoplasia. Cancer Prev Res (Phila).2013 April. PMID: 23592738

September 2013 l www.ihpmagazine.com 23

industry news Rotary and Gates Foundation extend fundraising agreement to end polio

Rotary International and the Bill & Melinda Gates Foundation announced an extension of their existing fundraising partnership that could generate up to US$525 million in new money for polio eradication as the global effort to end this crippling disease enters its critical endgame phase. Under the new agreement, announced before an audience of more than 20,000 Rotary members from 160 countries gathered in Lisbon for the humanitarian group’s annual convention, the Gates Foundation will match 2 for 1 every new dollar Rotary commits to polio eradication up to $35 million per year through 2018. All funds raised will support crucial immunization activities in polio-affected countries. These are part of a comprehensive six-year plan to eradicate both wild poliovirus and vaccine-derived virus announced by the eradication initiative during the Global Vaccine Summit in Abu Dhabi. At the Summit, global leaders and individual philanthropists signaled their confidence in the endgame plan by pledging $4 billion, nearly three-quarters of the plan’s projected $5.5 billion cost. They also called upon additional donors to commit the additional $1.5 billion needed to ensure eradication. Since then, the government of Australia, and now Rotary, are committing funding toward the remaining $1.5 billion gap through 2018.

1 in 4 Canadians with diabetes experience significant emotional distress and 1 in 6 report feelings of discrimination

Results from the global Diabetes Attitudes, Wishes and Needs 2 study (DAWN2™) show that 28 per cent of Canadians living with diabetes have experienced significant emotional distress and 15 per cent have felt discriminated against due to their disease. Results from the DAWN2™ study were presented today at the 73rd Scientific Sessions of the American Diabetes Association (ADA). DAWN2™ represents opinions from more than 15,000 people living with, or caring for people with diabetes in 17 countries across four continents. The study assessed a wide range of psychosocial indicators of diabetes care, including discrimination and the impact it has on a person’s emotional wellbeing. Key Canadian results from the DAWN2™ study include: More than 12 per cent of Canadians with diabetes had possible depression. Twenty-seven per cent of family members reported a significant burden on the family related to diabetes. Eighty-nine per cent of Canadian respondents living with diabetes had attended a diabetes education program or activity. More than 35 per cent of family members had ever attended a diabetes education program or activity. DAWN2™ will help stimulate much-needed discussion between healthcare providers, patients and their families, and lead to significant improvements in the management of diabetes.

Long-term donor support helps fund cancer breakthrough

Two of the world’s most acclaimed cancer researchers, Drs. Tak Mak of the Princess Margaret Cancer Centre, and Dennis Slamon of the University of California, Los Angeles, shared news of a major breakthrough in the decade-long pursuit to develop a new class of “sharpshooter” cancer drugs. Together they have submitted an Investigational New Drug (IND) application to the Food and Drug Administration for a new drug they have developed based on our research of a target enzyme, PLK4, which plays a crucial role in the process of cell division, particularly in cancer cells. This new drug, CFI400945, will enter clinical trials phase in the months ahead. In the lab, it has been shown to effectively inhibit the growth of human breast and ovarian cancers as well as colorectal, glioblastoma, lung, melanoma, pancreatic and prostate cancers. Drs. Mak and Slamon are very confident about their submissions to the FDA and Health Canada and anticipate that, following a successful regulatory review, the research team will be able to move quickly to the clinical testing stage.

Canadians look to their employers to navigate public-private healthcare issues

Over half of Canadian employees (55 per cent) struggle with chronic illness or injury and subsequently place a greater burden on the Canadian healthcare system. As this issue becomes prevalent, Canadians look to their employers for assistance in navigating the bureaucratic maze between the private and public healthcare systems. According to the 16th annual edition of The Sanofi Canada Healthcare Survey, nearly two-thirds (61 per cent) of employees who have yet to experience the system expect their plan sponsor to provide a high level of support. According to the survey, both plan members (81 per cent) and employers (90 per cent) acknowledge the importance of workplace-based health promotion programs to maintain the sustainability of the public healthcare system over the long-term. As such, provision of public programs in the workplace could be part of the solution to disease prevention and the management of chronic illness. Three-quarters (74 per cent) of employees indicate they would like their workplaces to allow public health programs such as flu shot clinics, disease screenings or health risk assessments to be available on-site during work hours. As well, close to nine in 10 (88 per cent) report that if there were on-site screening for a condition they were personally concerned with, they would be likely to participate. Plan sponsors are increasingly open to public and disease prevention programs in the workplace. Nine in 10 (91 per cent) say they would implement immunization clinics if supported by tax incentives, while a similar number indicate they would offer workplace-based health risk screening (87 per cent) and chronic disease prevention programs (88 per cent) pending increased government or public health support.

24 www.ihpmagazine.com l September 2013

NPN(s): 80015104 and 80038453 (50 Billion bacteria)

Pharmacology Potential Mecanisms of Action It was shown that L. acidophilus CL1285® and L. casei LBC80R® strains have an excellent gastrointestinal survival rate. In fact, starter cultures resist to a pH of 2.5 and, when the strains are encapsulated with enteric coating, they can resist a pH of 1.5 for 2 hours (unpublished data). Both strains survived to a high concentration of bile salt. This resistance allows a safe delivery of the probiotics to the GI tract and results in a production of antimicrobial molecules such as organic acids or bacteriocins. These molecules have been shown to directly eliminate various pathogenic bacteria such as C. difficile, E. faecium, E. faecalis, E. coli O157:H7, L. monocytogenes and methicillin-resistant S. aureus (MRSA). Moreover, secretion of an unknown metabolite was shown to reduce the cytotoxicity of toxin A/B secreted by C. difficile. Finally, administration of the CL1285® starter culture modulates the fecal microbiota by increasing the total lactic acid bacteria and total anaerobe count and reducing the Staphylococcus sp. count.

Health Claim Helps to reduce the risk of Clostridium difficile associateddiarrhea in hospitalized patients. Helps to reduce the risk of antibiotic-associated diarrhea. Probiotic that forms part of a natural healthy gut flora. Provides live microorganisms that form part of a natural healthy gut flora. Probiotic that contributes to a natural healthy gut flora. Provides live microorganisms that contribute to a natural healthy gut flora. Probiotic to benefit health and/or confer a health benefit. Provides live microorganisms to benefit health and/or to confer a health benefit.

Supplied Bio-K+® guaranties a minimum of 50×109 L. acidophilus CL1285® and L. casei LBC80R® per capsule at expiration date. These bacteria are live and protected with an enteric coating. Lyophilized bacteria are the result of fermentation, concentration and freeze-dry processes. A mixture containing a predetermined concentration of lyophilized bacteria, cellulose, ascorbic acid, and magnesium stearate is prepared. This mixture is then added in a vegetable cellulose capsule pigmented with colloidal silicone dioxide. Then, the capsule is enteric coated. Each capsule contains: ≥50×109 live strains of L. acidophilus CL1285® and L. casei LBC80R®. Nonmedicinal ingredients: ascorbic acid, cellulose, ethylcellulose, hypromellose, magnesium stearate, medium chain triglycerides, silicone dioxide, sodium alginate and titanium dioxide. Bottles of 15 or 250. A box contains 10 or 100 groups of 10, individually wrapped capsules in blister aluminumsealed sheets. Refrigerate at 4°C for maximum activity.

(100 Billion bacteria)

Contra-indications • Do not use if you are experiencing nausea, fever, vomiting, bloody diarrhea or severe abdominal pain; • Do not use if you have an immune-compromised condition (e.g. AIDS, lymphoma, patients undergoing long-term corticosteroid treatment); • Discontinue use and consult a health care practitioner if symptoms of digestive upset (e.g. diarrhea, nausea and vomiting) occur, worsen, or persist beyond 3 days; • Do not use if you are taking streptomycin.

Warnings • May contain traces of milk solids. Do not use this product if you are allergic to milk; • Do not use if seal is broken; • Inform your health care practitioner if you are using this product; • Keep out of reach of children.

Precautions Bio-K+® capsules should be swallowed whole. To preserve the enteric coating properties, do not chew, crush or open the capsules. It is safe to take Bio-K+® capsules for a prolonged period of time.

Overdose For management of a suspected drug overdose, CPhA recommends that you contact your regional Poison Control Centre. See the eCPS Directory section for a list of Poison Control Centres.

Dosage Recommended Dosage During Antibiotic Therapy • 2 capsules per day for the duration of the antibiotic treatment, and for five days after the treatment is completed. • The capsule should be taken at least two hours after antibiotic administration.

industry news Pharmax™ topical creams use exclusive patented trans-dermal Delivra™ technology

Pharmax™, a leading-edge, comprehensive line of professional grade nutraceutical products announced its Topical PRO™ series of creams use the innovative clinically studied Delivra™ trans-dermal technology from Delivra Inc. Following a recent multi-million dollar investment, this unique technology and specific Pharmax™ products will be the subject of a large scale research project spearheaded by Dr. Joseph Gabriele, the developer of the Delivra™ technology and a close and long-time collaborator of Pharmax™. The Delivra™ trans-dermal technology takes advantage of established interactions between natural substances and human cellular and nerve tissues to address pain management without the side effects associated with typical interventions. “In 2011, we were first-to-market exclusively for the healthcare practitioner segment with novel natural topical creams using the Delivra delivery system,” said Yves Yau, Head of the Pharmax™ brand. “We are proud of this latest advancement that emphasizes our ongoing commitment to provide only the highest quality, research-driven products offering cutting-edge ingredients. The new research project and our close collaboration with Dr. Joseph Gabriele will continue to place Pharmax™ at the forefront of trans-dermal technology.”

GeneDx to launch comprehensive breast cancer genetic test

GeneDx, one of the world’s foremost genetic testing laboratories and a subsidiary of Bio-Reference Laboratories, Inc. announced today its intention to launch a suite of comprehensive genetic tests for inherited cancers including BRCA1 and BRCA2 genes. GeneDx, which was the first commercial laboratory to utilize next generation sequencing technologies to answer meaningful clinical questions in cardiology, neurology, ophthalmology, among other clinical areas, will now bring its expertise and reputation for service to inherited cancers and will offer a 27-gene panel for breast and ovarian cancers. GeneDx will also provide next generation sequencing based multi-gene panels for gastrointestinal and colorectal cancers, pancreatic cancer, endometrial cancer and renal cell carcinoma. GeneDx has distinguished itself and gained the trust of the genetics community for its clinical and scientific expertise and experience. Founded in 2000 by geneticists and still managed today by geneticists, GeneDx started offering Whole Exome Sequencing in 2012 to help end the diagnostic odyssey for families who for years have been looking for a molecular diagnosis. Currently, GeneDx offers testing for more than 350 genetic disorders, and has over 30 board-certified geneticists and genetic counselors on staff available to physicians to address their concerns and questions about genetic testing.

Astellas introduces new option for men living with advanced prostate cancer

Xtandi™ (enzalutamide capsules) is now available in Canada. Health Canada approved Xtandi for the treatment of patients with metastatic castration-resistant prostate cancer, or mCRPC, who have received prior docetaxel therapy (chemotherapy medication). The announcement was made today by Astellas Pharma Canada, Inc., the Canadian subsidiary of Tokyo-based Astellas Pharma, Inc. Prostate cancer is the most common cancer to affect Canadian men, generally 40 years of age and older, with one in seven developing the disease in their lifetime. Most often, initial presentation of the disease may be asymptomatic or show minimal symptoms. However, approximately 10-20 per cent of cases will present with metastatic disease and another 33 per cent with early stage disease will go on to develop metastatic disease. The efficacy and safety of Xtandi were assessed in a randomized, placebo-controlled, multinational phase III clinical trial, called AFFIRM, that included eleven Canadian trial sites across the country. A total of 1,199 patients with mCRPC who had previously received docetaxel were randomized 2:1 to receive either Xtandi orally at a dose of 160 mg once daily (N = 800) or placebo (N = 399). Patients with a history of seizure, taking medications known to decrease the seizure threshold, or with other risk factors for seizure were excluded from the clinical trial. The primary endpoint of the trial was overall survival.

Statement from the Canadian Medical Association on new regulations on Medical Marijuana

A statement by the president of the Canadian Medical Association was provided recently. Canada’s doctors worry that the announcement of new regulations to govern the use of medical marijuana ignores the fact that there is no clinical evidence to back up its use as a medical therapy. This approach runs contrary to Canadians’ position on this issue as reported in an Ipsos Reid poll conducted for the CMA earlier this year. The poll found that 85 per cent of Canadians believe that medical marijuana should go through the same rigorous testing and approval as other medicines. Marijuana is a complex substance with strains that vary greatly in power and effect, but we have no information on potency, dosage or how it interacts with other therapies. The beneficial effects of marijuana have not been rigorously tested and it has a huge potential to cause harm. With the federal government vacating its role, there is no one to certify that the drug will not harm the patient. The Ipsos Reid poll also found that almost eight in 10 Canadians agreed that Health Canada, as the body that approves prescription medicines for safety and efficacy, should maintain its current role in authorizing the use of medical marijuana for patients. The use of medical marijuana has grown because there aren’t better treatments for people battling chronic pain. This is an area that definitely needs greater attention. The federal government will not help address this lack by abdicating its responsibility to protect the health of Canadians. September 2013 l www.ihpmagazine.com 27

PROGRESSIVE NUTRITIONAL THERAPIES VEGESSENTIAL ALL IN ONE VegEssential™ combines the benefit of an entire cupboard full of supplements with the ease of consuming a single smoothie. This simple to use all-in-one formula not only provides unmatched nutritional density, it also provides unmatched convenience. VegEssential™ embraces the wisdom of consuming an alkaline-forming, whole-food diet and draws on almost 100 plant-based ingredients to deliver an incredible spectrum of both micro and macro nutrients. Vegetable protein intake was inversely related to blood pressure. This finding is consistent with recommendations that a diet high in vegetable products be part of healthy lifestyle for prevention of high blood pressure and related diseases (Elliot, et al 2006). Elderly women with a high dietary ratio of animal to vegetable protein intake have more rapid femoral neck bone loss and a greater risk of hip fracture than do those with a low ratio. This suggests that an increase in vegetable protein intake and a decrease in animal protein intake may decrease bone loss and the risk of hip fracture (Sellmeyer, et al 2001). An elevated level of total plasma homocysteine (tHcy) is considered to be a predictor of the mortality risk for all diseases. Panunzio et al (2003) investigated whether supplementation of concentrated fruit and vegetables is able to decrease tHcy levels. Twenty-six subjects participated in a cross-over design intervention trial, receiving 2 capsules of fruits and 2 capsules of vegetables a day for 4 weeks, then acting as his/her own control for another 4 weeks. It was revealed that plasma tHcy concentration was decreased as a result of taking a powdered fruit and vegetable extract on a daily basis, reducing a risk factor causally linked to chronic disease. Cao et al (1998) examined whether a diet rich in fruit and vegetables would affect the antioxidant capacity of human plasma. Thirty-six healthy nonsmokers consumed 2 sets of control diets providing 10 servings of fruits and vegetables each day (for 15 days) with or without an additional 2 servings of broccoli each day on days 6-10. It was observed that increased consumption of fruit and vegetables could increase the plasma antioxidant capacity in humans. Vazir, et al (2006) evaluated the effect of a micronutrient supplement on mental function in children (aged 6 – 15 years). This double blind, placebo-controlled, matched-pair, cluster, randomized trial assessed a cohort of 608 children for intelligence, attention and concentration, memory, and school achievement, before and after 14 months of micronutrient supplementation. Results indicated that supplementation with a range of micronutrients significantly improved attention-concentration over the period of 14 months in children aged 6 – 15 years. The SHEEP study examined the association between the use a multivitamin supplements and the risk of myocardial infarction (MI). Results were based on data from a large population-based, case-control study of subjects aged 45 – 70 years. The study included 1296 cases (910 men, 386 women) with a first nonfatal MI and 1685 controls (1143 men, 542 women) frequency-matched to the cases by sex, age and hospital catchments area (Holmquist, et al 2003). The results from this study indicate that use of a multivitamin supplements may aid in the primary prevention of MI.

Dosage Indication: A factor in the maintenance of good health. Adults (≥ 18 years)

Suggested Use: Add 1 scoop of VegEssential™ into 350-400ml of the beverages of your choice.

Interactions There is insufficient research available regarding the safety of several of the herbal components in children, as a result the use of VegEssential is not recommended in children under 18 years of age (Jellin et al (2006)). Due to the potential of toxicity and adverse effects of some of the constituents, VegEssential is not recommended for use in pregnant or breastfeeding women (Jellin et al (2006)). Some the components in VegEssential may interact with medication, diseases and conditions, and/or lab test results. It is recommended that all ingredients be reviewed before use in an individual under medical supervision, taking prescription medication, suffering from a serious and/or pre-existing medical condition (Jellin et al (2006)).

Quality Assurance

Parameter Microbial Total Count Yeast & Mold Escherichia coli Salmonella sp Staphylococcus aureus Heavy Metal Arsenic Cadmium Lead Total Mercury Chemical Pesticides Solvents

Test

Specifications

USP USP USP USP USP

Less than 5,000 cfu/g Less than 100 cfu/g Negative Negative Negative

USEPA USEPA USEPA USEPA

< 1.0 ppm < 0.5 ppm < 1.0 ppm < 1.0 ppm

USP USP

Absent Conforms to limits

References Cao G, et al (1998). Increases in human plasma antioxidant capacity after consumption of controlled diets high in fruit and vegetables. Am J Clin Nutr, 68: 1081-1087. Elliott P, et al. Association Between Protein Intake and Blood Pressure: The INTERMAP Study. Arch Intern Med, Jan 2006; 166: 79 - 87

Holmquist C, et al (2003). Multivitamin Supplements Are Inversely Associated with Risk of Myocardial Infraction in Men and Women – Stockholm Heart Epidemiology Program (SHEEP). J Nutr, 133: 2650-2654. Jellin JM, et al (2006). Pharmacist’s Letter/Prescriber’s Letter th Natural Medicines Comprehensive Database.8 ed. Stockton, CA: Therapeutic Research Faculty. Sellmeyer, D. E., et al. 2001. A high ratio of dietary animal to vegetable protein increases the rate of bone loss and the risk of fracture in postmenopausal women. American Journal of Clinical Nutrition. 73(1): 118-122. Panunzio MF, et al (2003). Supplementation with fruit and vegetable concentrate decreases plasma homocysteine levels in a dietary controlled trial. Nutrition Research, 23: 1221-1228. Vazir S, et al (2006). Effect of micronutrient supplement on health and nutritional status of schoolchildren: mental function. Nutrition, 22: S26-S32.

industry news

Scientists clarify benefits and use Of Glycemic Index, Load and Response

An international committee of leading nutrition scientists from ten countries on three continents released an important Scientific Consensus Statement. They concluded that carbohydrate quality (measured by the glycemic index or GI) matters and that the carbohydrates present in different foods affect post-meal blood sugar differently, with important health implications. They also confirmed that there is convincing evidence from a large body of research that low glycemic index/glycemic load (GI/GL) diets reduce the risk of type 2 diabetes and coronary heart disease, help control blood glucose in people with diabetes, and may also help with weight management. The Committee recommended inclusion of glycemic index and glycemic load in national dietary guidelines and food composition tables, and that packaging labels and symbols on low-GI foods should be considered. They also confirmed low GI measurements complement other ways of characterizing carbohydrate foods (such as fiber and whole grain content), and should be considered in the context of an overall healthy diet.

New investigational treatment extends life of lung cancer patients with adenocarcinoma

New research on Canada’s number one cancer killer is further proof that patients need personalized treatments targeted to their specific type of lung cancer for better outcomes. Boehringer Ingelheim (Canada) Ltd. announced highly anticipated results from the Phase III LUME-Lung 1 study in patients with advanced non-small cell lung cancer (NSCLC). The primary endpoint was progression-free survival (PFS) and the results showed patients treated with nintedanib plus chemotherapy (docetaxel) lived for a median of 3.4 months before their tumour started to grow again, versus 2.7 months with docetaxel alone (HR 0.79; p=0.0019). The study also examined the secondary endpoint of overall survival (OS), and in the process uncovered a specific group of patients who respond particularly well to the combination therapy. The trial examined a sub-group of patients with adenocarcinoma histology - the most common type of NSCLC. It showed that patients with adenocarcinoma whose disease progressed during first-line therapy or shortly after lived for an additional 2.3 months in the nintedanib combination treatment arm versus with docetaxel alone. Specifically, the median overall survival (the gold standard measure of success in lung cancer treatment) was 12.6 months in the nintedanib combination treatment arm versus 10.3 months with docetaxel alone (HR 0.75; p=0.0073).

Abbott Introduces its RealTime Molecular Test for Human Papillomavirus (HPV) in Canada

Abbott announced it has been granted license by the Medical Device Bureau of Health Canada, for its RealTime High Risk HPV molecular diagnostic test for the detection of human papillomavirus (HPV), the leading cause of cervical cancer. Abbott’s RealTime High Risk HPV test is designed to detect 14 high-risk HPV genotypes with simultaneous detection of HPV genotypes 16 and 18 in one assay. HPV genotypes 16 and 18 are known to pose the highest risk to progress to cervical cancer. “Molecular detection of high-risk HPV infections, in women over the age of 30, is an important adjunct to cervical cancer screening in Canada,” said Barbara Romanowski, MD, FRCPC, Clinical Professor, University of Alberta, Edmonton, Canada. “Women with abnormal pap tests, especially those at borderline, can be tested with a rapid HPV DNA test to detect the presence of high-risk HPV,” said Judy Yu, Ph.D., director, scientific affairs, Molecular Diagnostics, Abbott. “HPV DNA tests, like the Abbott RealTime High Risk HPV test, combined with high specificity of cytology, can direct the appropriate management strategies for women with abnormal pap results.” HPV is a group of viruses with more than 150 different genotypes. Fourteen genotypes are classified as high-risk HPV because of their association with cervical cancer. HPV genotypes 16 and 18 are known to pose the highest risk to progress to cervical cancer and are found in approximately 70 percent of cervical cancer cases.

Canadian Medical Association and Canadian Pharmacists Association release e-prescribing joint statement

The Canadian Medical Association (CMA) and the Canadian Pharmacists Association (CPhA) have approved a joint statement on the future of e-prescribing that aims to have all prescriptions for Canadians created, signed and transmitted electronically by 2015. The joint statement identifies the core principles that must be captured in a pan-Canadian system of e-prescribing, as well as its potential benefits and challenges. “Canada’s pharmacists and physicians have set forth a bold vision for the future of e-prescribing in Canada,” said Dr. Anna Reid, CMA president. “However, now that bold vision must be matched with bold action to advance e-prescribing for the benefit of patients.” The CMA and CPhA developed the joint statement as a first step in bringing partners together to develop a strategy and action plan. The two associations recognize that, while achieving full e-prescribing functionality by 2015 will not necessarily be an easy vision to achieve, the benefits to patients, health care providers, and the overall health system are undeniable and well worth the effort.

30 www.ihpmagazine.com l September 2013

calendar September

September 20 Biopuncture with Complex Homeopathics Organized by: Pascoe Toronto, Ontario For more information, visit http:// www.pascoecanada.com September 21-28 Organic Week 2013 Organized by: Organic Week Events Vary By Location For more information, visit http://www.organicweek.ca September 25 IBS, Crohnâ&#x20AC;&#x2122;s and Celiac Diseases Teleconference Organized by: Seroyal Online Webinar For more information, visit http://www.seroyalseminars.com

October

October 3-5 Come to your Senses: Providing the Key to Access Ability: The Sensory Connection Organized by: MukiBaum Foundation Toronto, ON For more information, please visit: http://cometoyoursensesconference. wordpress.com/ October 3-6 CHFA East Conference Organized by: CHFA Toronto, ON For more information, please visit: https://www.chfa.ca/ tradeshows/chfa-east-2013/ October 4-6 2013 Lifestyle Medicine Summit Organized by: Metagenics Chicago, IL For more information, please visit: www.metagenics.com

October 4-6 The Evolution of Disease & Biotherapeutic Drainage Organized by: Seroyal Toronto, ON For more information, please visit http://www.seroyalseminars.com October 7-9 2nd International Summit on Toxicology Organized by: OMICS Group Las Vegas, Nevada For more information, please visit http://www.omicsgroup.com/ conferences/toxicology-2013/ October 10-13 2nd International Congress on Controversies in Stem Cell Transplantation and Cellular Therapies (COSTEM) Organized by: FIGO Berlin, Germany For more information, visit http://www. comtecmed.com/cigi/2013/default.aspx October 16 Convallaria and Crataegus in the treatment of Cardiac Dysfunction Organized by: AARM Online Webinar For more information, visit http:// restorativemedicine.org/cme-webinars/ October 19-20 Successful Case Management of Chronic Disease Workshop Organized by: Seroyal Seattle, WA For more information, please visit http://www.seroyalseminars.com October 24 Internal Medicine for Primary Care Organized by: MCE Conferences Sonoma, CA For more information, visit http://www.mceconferences.com/ medical-conferences.php

October 26 CHEST 2013 Organized by: CHEST Chicago, IL For more information, visit http://www.chestnet.org/accp/events

November

November 2 Personalizing Nutritional Protocols Based on Lab Test Results Organized by: Metagenics Rogers, Arkansas For more information, please visit http://www.metagenics.com November 7-10 FirstLine Therapy Certification Organized by: Metagenics New York, NY For more information, please visit http://www.metagenics.com November 20 Effective Herbal Therapies for Polycystic Ovarian Syndrome Organized by: AARM Online Webinar For more information, visit http:// restorativemedicine.org/cme-webinars/ November 30 Diabetes Boot Camp for Primary Care Organized by: MCE Conferences Florida For more information, visit http://www.mceconferences.com/ medical-conferences.php

December

December 5-8 FirstLine Therapy Certification Organized by: Metagenics Austin, TX For more information, please visit http://www.metagenics.com December 18 Integrating Bio-Identical Hormones and Herbs for Menopausal Therapy Organized by: AARM Online Webinar For more information, visit http:// restorativemedicine.org/cme-webinars/

September 2013 l www.ihpmagazine.com 31

D R . I R V I N G K I R S C H T O S P E A K AT

2013 DR. ROGERS PRIZE AWARD GALA DINNER & COLLOQUIUM Research shows antidepressants have little difference in effect from placebo by Kate MacDonald The 2013 Dr. Rogers Prize for Excellence in Complementary and Alternative Medicine will be celebrated with a gala award dinner and free afternoon colloquium in Vancouver on September 26, 2013. While the list of frontrunners for the biennial $250,000 prize is a closely held secret, the work of speaker, Dr. Irving Kirsch, Associate Director of the Program in Placebo Studies at Harvard Medical School and author The Emperor’s New Drugs: Exploding the Antidepressant Myth, is much more well-known. Kirsch’s research, based on analysis of the drug companies’ own data, questions the effectiveness of antidepressants, showing little difference in effect from placebo. His provocative findings compelled the UK National Health Service to complete their own review of antidepressant clinical trials, resulting in a dramatic revamp of the way antidepressants are prescribed in the United Kingdom.

In addition to relating his experiences as a troublemaker during his dinner presentation, Dr. Kirsch will open the colloquium “Exploring the Mind-Body Continuum” with a brief description of the placebo effect and its significance, setting the stage for further exploration of the day’s topic. Given the latest revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), which lowers the criteria for diagnosis of some mental health conditions while broadly expanding the definitions of others, Dr. Kirsch’s insights should be of great significance to the general public and medical community alike. The free afternoon colloquium takes place between 1 to 5 pm at the Fairmont Waterfront Hotel, with the reception and award dinner to follow in the evening. Registration and ticket information for both events can be found online at www.drrogersprize.org.

Dr. Rogers Prize Gala Award Dinner REGISTER Thursday, September 26, 2013 at the Fairmont Waterfront Hotel

NOW!

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Free Afternoon Colloquium: Exploring the Mind-Body Continuum

2013 winner of the $250,000

The afternoon colloquium, featuring a

Dr. Rogers Prize for Excellence

cameo appearance by Dr. Irving Kirsch,

in Complementary and

will examine a range of viewpoints on

Alternative Medicine. This year’s

the mind-body continuum, including

keynote presentation will be by

recent research by eminent panellists such

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as Dr. Jeffery Dusek, co-author of the

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the Antidepressant Myth. Early bird ticket sales end on August 31 Individual tickets: $125 • Table of ten: $1,250

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2013-07-24 10:49 am

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33 www.ihpmagazine.com l September 2013

Vision Essentials Vision Essentials from Julian Whitaker, MD, combines 15 powerful, clinically researched nutrients including black currant, lutein, beta-carotene and ginkgo biloba to help improve night vision, reduce eye fatigue, promote clear vision, reduce glare and reduce the risk age-related eye problems. Available at Health Food Stores PNO.CA

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Cellular Detox is an effective compliment to your detox regimen; detoxification enhances immunity, cardiovascular health, reduces allergies, and has anti-inflammatory and anti-cancer effects. SGS (sulforaphane glucosinolate) inhibits tumor formation and supports phase II detoxification. D-glucarate prevents glucuronidation and probiotic BB-536 promotes the detoxification of carcinogens and toxins in the liver.

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product profiles

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Metagenics Launches MitoVive™

KLEAN Athlete™

MitoVive is an exciting new product designed to support healthy functioning of the mitochondria— the powerhouses of the cell—and overall cell activity to help relieve muscle tenderness and discomfort. It’s an ideal complement to a wide range of protocols to promote neuromuscular health and support healthy aging. MitoVive is provided in a great-tasting, orange-flavored powder that mixes easily with water. Each jar contains 30 servings. Metagenics.com • 800.268.6200 Canada

Klean Athlete™ is a truly unique dietary supplement line formulated for the specific needs of athletes. Every product is NSF Certified for Sport® and tested clean of banned substances providing your patients with everything they need and nothing they don’t. Klean Athlete™ products are free of yeast, wheat, gluten, soy, corn, sugar and starch, they contain no artificial colouring, flavouring or preservatives. You can feel confident about offering safer nutritional supplements that support a healthy lifestyle and peak performance.

PASCOLEUCYN® – A Natural Flu Prevention PASCOLEUCYN® is a non-specific immune remedy that increases the body’s natural defenses in acute and chronic infections. It relieves symptoms due to colds and flu such as headaches, stuffy nose, sore throat, cough and fever. A prophylactic intake of PASCOLEUCYN® can give your patients broad protection against colds and flu. Recommend the ampoules once or twice per season for general defense, and the drops when others around your patient are starting to get sick. For complete dosing suggestions for all ages, visit www.pascoecanada.com. Made in Germany and quality assured, with 60 years of confidence.

Liposomal Glutathione – Enhanced Absorption The Liposomal form of glutathione offers an enhanced form for improved absorption. The liposomal form protects glutathione bonds from degradation that may occur during digestion. Glutathione is a powerful antioxidant key in cellular function and liver support.

35 www.ihpmagazine.com l September 2013

PASCOFLAIR® – Stay relaxed and alert! PASCOFLAIR® is a unique preparation containing 425mg of Passionflower extract. As a widely used herb, Passionflower provides fast and effective relief. Studies have shown passionflower has anxiolytic effects equal to diazepam, oxazepam, and mexazolam with a better safety profile than these medications. Extracts from passionflower have also shown promise in the treatment of opiate, benzodiazepine, and nicotine withdrawal in mice and humans. PASCOFLAIR® won the 2009 “Apotheken-Award” for Natural Medicine – an honor chosen by German pharmacists each year for the best in natural medicine.

Dr Tris

cover story

30 years of integrative medicine, and counting… By Philip Rouchotas MSc, ND Photographs by Aaron Pedersen

It is always a special thing when the IHP team has the privilege of showcasing a true pioneer of integrative medicine; Dr Trethart’s 30 year tenure of delivering world- class integrative care to the Edmonton, Alberta community is indeed such an occasion. In 2013, anyone interested in educating themselves in integrative medicine has dozens of accredited academic institutions, thousands of PubMed indexed clinical trials and review articles, and a lifetime of web- based resources to call upon. As Dr Trethart wrapped up his medical residency in 1982, such well- developed resources of education simply did not exist.

Trethart, MD Named during his medical training “most likely to administer IV carrot juice and bran muffins”, his vision of applying integrative medical techniques was no mystery to his colleagues. Travelling such a path was invariably an infinitely greater challenge in 1982 than it is today. Thanks to the tireless efforts of Dr Trethart and others, so many of us today have the relatively easy ability to enter the discipline of integrative medicine and thrive.

September 2013 l www.ihpmagazine.com 37

cover story

As Dr Trethart worked on his undergraduate training, he found himself suffering from a long list of common, chronic ailments;

While operating a truly eclectic practice, Dr Trethart describes his facility as “anti aging focused – the practice of aging with dignity”. fatigue, aches/ pains, insomnia, depression. He came across William Dufty’s book Sugar Blues and decided to attempt to eliminate sugar from his diet. After routing through all his cupboards and throwing away any food containing sugar, he realized he had no food left! The “radical” change in his diet to eliminate sugar quickly, within a handful of weeks, resolved many of the chronic concerns he was experiencing. An inclination towards diet and lifestyle as medicine, as opposed to a reliance on pharmacotherapy, was firmly entrenched in Dr Trethart upon his arrival at

38 www.ihpmagazine.com l September 2013

the University of Manitoba school of medicine. Dr Trethart embraces all tenants encompassing the discipline of integrative medicine. Truly patient-centred, individualized, integrated care is delivered. The facilities name? As unassuming as the facilities only physician; Dr Trethart’s Clinic. The system of care delivery is impressive, and certainly worth noting. An initial visit is utilized to provide a classic intake with physical exam, and any appropriate conventional labs are ordered. The second visit reviews the findings of the physical and basic lab work, integrative lab tests are discussed, and a basic diet/ supplement program is initiated. Dr Trethart is a firm believer in the use of a myriad of integrative diagnostic tests, sighting them as key in the process of doctor – as – detective, necessary to achieve truly individualized patient care. Food sensitivity panels are ordered on virtually every patient. Thereafter, comprehensive stool analysis, provocative heavy metal assessment, detailed nutrition profiles, and others are utilized frequently. Dr Trethart described his practice as a “resort practice”. By this he meant patients come to him as a last resort. Integrative healthcare providers across the country are no doubt familiar with such a scenario. In his own words “I see more interesting, unique, and difficult cases in one day than a GP sees in six months”. I wholeheartedly agree Dr Trethart, and that isn’t something they teach us in ND school, either. While operating a truly eclectic practice, Dr Trethart describes his facility as “anti aging focused – the practice of aging with dignity”. Dr Trethart is the only clinician in the facility, yet the facility services over 125 patients per week, in addition to 30-40 IV therapies per week. This impressive patient volume is co-managed by an incredible and dedicated team of professionals; two executive administrators act as office managers, yet also involve themselves as patient coaches, fielding phone questions from patients, running patients through the process of specimen collection for integrative diagnostic tests, etc... There are also two receptionists and an RMT. The on- site

cover story

dispensary utilizes a manager and three support staff. A nurse and nurse assistant round out the team, principally managing the IV room of the facility. Common IV therapies employed include EDTA, DMPS, Plaquex, IV-C, Meyer’s, bio-oxidative therapies, glutathione, and others. Dr Trethart is also a firm supporter of breast thermography, running the technique in-house, and utilizing a Toronto-based lab for interpretation of outcomes.

We asked Dr Trethart what it was like starting an integrative practice so many years ago, where he turned for training, if he has experienced scrutiny from regulators along the way, and if he has noticed a change in perception of his work from colleagues and/ or regulators over the years. He explained that even from the days of his residency there were “watchful eyes” looking over his shoulder, because he would provide lifestyle advice while on rotation. Thereafter he described “extensive scrutiny”

September 2013 l www.ihpmagazine.com 39

cover story

From left to right, back row: Tris Trethart, Tracy Willis, Nichole Abma, Cindy Caron, John Trethart, David Carr; front row: Karen Fech, Nelly Velasco, Monique Da Costa, Jade Gionet, Lesley Erskine.

Dr Trethart described his practice as a “resort practice”. By this he meant patients come to him as a last resort. Integrative healthcare providers across the country are no doubt familiar with such a scenario. In his own words “I see more interesting, unique, and difficult cases in one day than a GP sees in six months”. from the provincial regulator, beginning in 1983 with an inquiry because he referred a war vet with back pain to see a chiropractor. In honesty, I expressed to Dr Trethart that relative to other integrative healthcare providers across Canada, his interactions with regulators in fact seem minimal; he was somewhat relieved to hear such a comment. From a perspective of his colleagues, he did note that over the years there has been a consistent increase in referrals he obtains from

40 www.ihpmagazine.com l September 2013

local conventional practitioners. He still feels however the gap between conventional and integrative providers remains very large. I undertake these interviews with leading Canadian integrated healthcare providers to create awareness among doctors across Canada of the important, tireless, selfless, and immenselyvaluableworkpeoplelikeDrTrethart perform daily. Never have I been so directly impacted by an interview as I was

cover story

by Dr Trethart. For every point or two I jotted down about him and his practice, I was furiously writing pages of notes to immediately implement in my private practice. Dr Trethart is a wealth of knowledge and experience. He is truly among the most gifted of integrated healthcare providers in the country. He made a tragic mistake during our interview, however; he informed me that his facility is not visited by ND preceptors! Rest assured Dr Trethart, I am confident you will be swarmed with them in the years to come! You have been keeping yourself a secret for far too long... Thank you for allowing us to showcase your efforts to our readership. Thank you for traveling down this path in a time when it more resembled a brick wall than a path. And thank you in advance for opening your doors to aspiring ND’s… You will be seeing them soon. ■

Dr Trethart is a firm believer in the use of a myriad of integrative diagnostic tests, sighting them as key in the process of doctor – as – detective, necessary to achieve truly individualized patient care.

September 2013 l www.ihpmagazine.com 41

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The Mediterranean diet is associated with markedly lower risk of several chronic diseases, including cardiovascular disease and diabetes (Eustruch 2006, Interact Consortium 2011, Nordmann 2011), and a high fruit and vegetable diet has been shown to reduce risk of cancer (Block 1992), in large part due to high amounts of combined phytonutrients. Phytonutrients have been shown to confer beneficial health effects through numerous mechanisms, including modulation of signal transduction pathways, antioxidant properties, and through hormonal effects. PhytoMulti contains over 20 of these plant substances, including: lutein, zeaxanthin, acacia nilotica, and extracts of artichoke leaf, grape seed extract, green coffee, green tea, citrus bioflavonoids, resveratrol, prune skin, watercress, rosemary, pomegranate, lycopene, cinnamon, bitter melon, and blueberry. Multivitamin supplementation has been shown to benefit a variety of physical and cognitive parameters particularly in children, pregnant women or women who may become pregnant, individuals under increased stress, individuals with poor absorption, and the elderly. In pregnancy, supplementation with a folic acid containing multivitamin has been shown to reduce risk of complications such as placental abruption, preeclampsia, in addition to decreasing risk of congenital defects including neural tube defects, anencephaly, myelomeningocele, meningocele, oral facial cleft, structural heart defects, limb defects, urinary tract anomaly, and hydrocephalus when used prior to conception and during the first trimester (Wilson 2007). Periconceptional multivitamin use in lean women has been shown to decrease the risk of small-for-gestational-age (SGA) under the 5th percentile by up to 46% compared to non-users (OR=0.54, 95% CI), and has been associated with a 71% reduction in preeclampsia risk (OR=0.29, 95% CI) in lean women, users versus non-users (Catov 2007; Bodnar 2006). Periconceptional multivitamin use has also been associated with reduced risk of several pediatric cancers, including leukemia (OR=0.61) (39% reduced risk); pediatric brain tumors (OR=0.73) (27% reduced risk); and neuroblastoma (OR=0.53) (47% reduced risk) in a recent metaanalysis (Goh 2007). In patients under high levels of psychological stress, use of a multivitamin has been shown improve perceived levels of stress and psychometric parameters. Gruenwald et al (2002) found that use of a multivitamin for 6 months resulted in a 40.7% overall improvement in self rated stress levels using a psychologicalneurological questionnaire to assess “psycho-organic, central vegetative, and somatic discomforts.” Other outcomes included a 29% decrease in frequency of infections and 91% decrease in gastrointestinal discomfort. Schlebusch et al (2000) found similar benefit on various psychometric parameters in a 30 day trial (1997), and Harris found that multivitamin supplementation can improve measures of mood, stress, and alertness in older men (2011). Importantly, supplementation with a spectrum of B vitamins has also been shown to reduce ratings of workplace stress (Stough 2011). Several trials have shown increased cognitive performance in children taking a multivitamin supplement. Benton et al (1988) found a significant increase in nonverbal intelligence in children taking a multi versus those taking placebo after 8 months’ intervention. In a 14 month study of 608 children, Vazir et al (2006) found a significant increase in attention-concentration increment scores in those supplemented with a micronutrient-fortified beverage versus those receiving placebo. Additional benefits demonstrated in children include a reduced mean duration (5.0 versus 7.5 days, supplement versus placebo) of several common childhood illnesses including such as fever, cough and cold, diarrhea, and ear infections (Sarma 2006). In the elderly, multivitamin supplementation has been shown to significantly improve status of such nutrients as vitamin D, vitamin B6, vitamin B12, folate, vitamin C, vitamin E, zinc, and selenium (McKay 2000; Girodon 1997). In addition, supplementation has also been found to significantly reduce rates of infection in the elderly, as found a trial in 81 subjects given various supplemental combinations of micronutrients and followed over a 2 year period (Girodon 1997).

PhytoMulti: Active Ingredients* (per 1 tablet) Ingredient Vitamin A as retinyl acetate Vitamin A as carotenoids Vitamin E d-alpha tocopherol Vitamin C ascorbic acid Vitamin D3 cholecalciferol Vitamin K phytonadione Thiamine mononitrate

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Unit IU IU IU mg IU mcg mg

Riboflavin 7.50 mg Niacin 6.25 mg Niacinamide 18.75 mg Pantothenic acid 37.5 mg Vitamin B6 pyridoxine HCl 12.50 mg Calcium L-Mefolinate 400 mcg Vitamin B12 cyanocobalamin 120 mcg Biotin 250 mg Magnesium citrate 20 mg Chromium polynicotinate 100 mcg Copper citrate 500 mcg Iodine potassium iodide 75 mcg Manganese citrate 250 mcg Molybdenum aspartate 25 mcg Selenium aspartate 50 mcg Zinc citrate 7.50 mg * In addition to extracts of over 20 phytonutrients.

References Benton D, Roberts G. Lancet. 1988 Jan 23;1(8578):140-3. Block G, et al. Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutrition and cancer 1992;18(1):1-29. Bodnar LM, Tang G, Ness RB, Harger G, Roberts JM. Am J Epidemiol. 2006 Sep 1;164(5):470-7. Epub 2006 Jun 13. Catov JM, Bodnar LM, Ness RB, Markovic N, Roberts JM. Am J Epidemiol. 2007 Aug 1;166(3):296-303. Epub 2007 May 11. Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Fertil Steril. 2008 Mar;89(3):668-76. Epub 2007 Jul 10. Eustruch R, Martínez-González MA, Corella D, et al. Ann Intern Med. 2006 Jul 4;145(1):1-11 Girodon F, Lombard M, Galan P, Brunet-Lecomte P, Monget AL, Arnaud J, Preziosi P, Hercberg S. Ann Nutr Metab. 1997;41(2):98-107. Goh YI, Bollano E, Einarson TR, Koren G. Clin Pharmacol Ther. 2007 May;81(5):685-91. Epub 2007 Feb 21. Grieger JA, Nowson CA, Jarman HF, Malon R, Ackland LM. Eur J Clin Nutr. 2007 Nov 28. Gruenwald J, Graubaum HJ, Harde A. Adv Ther. 2002 May-Jun;19(3):141-50. Harris E, Kirk J, Rowsell R, Vitetta L, Sali A, Scholey AB, Pipingas A. Hum Psychopharmacol. 2011 Dec;26(8):560-7. InterAct Consortium. Diabetes Care. 2011 Sep;34(9):1913-8. McKay DL, Perrone G, Rasmussen H, Dallal G, Hartman W, Cao G, Prior RL, Roubenoff R, Blumberg JB. J Am Coll Nutr. 2000 Oct;19(5):613-21. Murphy MM, et al. Journal of the American Dietetic Association 2011:in press. Nilsen RM, Vollset SE, Rasmussen SA, Ueland PM, Daltveit AK. Am J Epidemiol. 2008 Apr 1;167(7):867-74. Epub 2008 Jan 10. Nordmann AJ, Suter-Zimmermann K, Bucher HC, et al. Am J Med. 2011 Sep;124(9):841-51.e2. Ribeiro ML, Arçari DP, Squassoni AC, Pedrazzoli J Jr. Mech Ageing Dev. 2007 Oct;128(10):577-80. Epub 2007 Aug 15. Sarma KV, Udaykumar P, Balakrishna N, Vijayaraghavan K, Sivakumar B. Nutrition. 2006 Jan;22(1 Suppl):S8-14. Schlebusch L, Bosch BA, Polglase G, Kleinschmidt I, Pillay BJ, Cassimjee MH. S Afr Med J. 2000 Dec;90(12):1216-23. Stough C, Scholey A, Lloyd J, Spong J, Myers S, Downey LA. Hum Psychopharmacol. 2011 Oct;26(7):470-6. Tanvetyanon T, Bepler G. Cancer. 2008 Jul 1;113(1):150-7. Vazir S, Nagalla B, Thangiah V, Kamasamudram V, Bhattiprolu S. Nutrition. 2006 Jan;22(1 Suppl):S2632. Wilson RD, et al. J Obstet Gynaecol Can. 2007 Dec;29(12):1003.

clinic profile

From left to right: Andrée Surette Poirier, RMT, Melissa Blake, ND, Blossom Bitting, ND, Sari LaBelle (HSI), CYT, Melanie Boudreau, Reception

The Pear Tree Clinic Leaders in W integration – promoters of regulation By Christopher Habib, ND Photographs by Aaron McKenzie Fraser

44 www.ihpmagazine.com l September 2013

e at IHP are pleased to cover The Pear Tree Clinic, located in Dieppe, New Brunswick. Dr. Melissa Blake, ND is the owner of the clinic. She graduated from the Canadian College of Naturopathic Medicine in 2006 and knew at that time that she wanted to return to the Maritimes. She first opened The Pear Tree in Sackville and then decided after 2 years to move to the larger Moncton area with hopes of growing The Pear Tree into a multi-disciplinary medical center. Dr. Blossom Bitting, ND joined Dr. Blake in 2009 and they have been practicing together successfully for the last 4 years.

Both NDs have recently become mothers and impressively still manage to service approximately 200 patient visits per week. The clinic is 3000 square feet and includes 6 treatment rooms, an infrared sauna, and a yoga studio. The other members of the clinic include Andrée Surette Poirier, RMT and Sari LaBelle (HSI), CYT. Andrée focuses her practice on stress reduction and stress management. She is also a Reiki Master Teacher and utilizes many different techniques in personalizing her treatments to her patient’s needs. Sari is a Life Coach, Yoga teacher, and Meditation instructor. She leads group sessions and helps her

clinic profile

patients actualize life goals through selfexploration, body and mind awareness, and creative expression. The Pear Tree Clinic is unique in that they are the only integrative clinic in their area that offers naturopathic services and other alternative health care services. Their team approach is reflected in the clinic slogan: “Pearing together, for your health and wellness.” Staying connected is important to the clinic team members. The team meets once a week to discuss clinic operations and upcoming events. During these meetings, they bring up challenging cases and work together to develop comprehensive, individualized plans. Their mission is to make an impact in the wellness of each person who walks through their door. They believe a team-based approach is the best way of achieving this. As a result, they put a significant effort towards networking and continually contact other local health care providers, in hopes of improving the health service options available for their patients. Naturopathic Doctors are not regulated in New Brunswick. Dr. Blake and Dr. Bitting try to bridge the gap between NDs and MDs by attending and hosting networking events, educating the public and other health care practitioners, and by providing high-quality holistic care to their patients. They are both members of the New Brunswick association of Naturopathic Doctors (NBAND). Dr. Blake is also a member of the Nova Scotia Association. New patients usually find the clinic through their website or online through the yellow pages. The practitioners also see a large amount of patients from word-of-mouth referrals and from external referrals. For new patients, the clinic’s receptionist is responsible for filtering primary health goals and then

directing the patient to the appropriate practitioner. Although both NDs enjoy general family practice, Dr. Blake’s practice focuses on cardiovascular health and oncology, while Dr. Bitting’s practice focuses on pediatrics and fertility. The NDs are usually the primary contact for

and St-Francis Herb Farm. They carry supplements from professional product lines, including AOR, Genestra, CanPrev, Vitazan, Thorne, and Restorative Formulations. They carry homeopathics from Boiron. Dr. Blake does all blood draws for the

Staying connected is important to the clinic team members. The team meets once a week to discuss clinic operations and upcoming events. patients and manage the addition of other practitioners as needed. If the patients present with musculoskeletal complaints or a high degree of stress, they usually refer to the massage therapist. If weight loss is a concern, they also suggest tailored yoga programs and will meet with the patients on an individual basis as well as in groups. The clinic has a natural health product dispensary. It includes custom tinctures using herbs from Viriditas

clinic and then sends out to labs such as Gamma-Dynacare Laboratories, Rocky Mountain Analytical, Doctor’s Data (especially for heavy metals), and Neuroscience. The clinic’s most popular lab test is Rocky Mountain Analytical’s IgG test for food allergies, followed by Vitamin D testing. Due to the lack of regulation, the public still has misconceptions about the ‘ND’ designation and other competing

September 2013 l www.ihpmagazine.com 45

clinic profile

Due to the lack of regulation, the public still has misconceptions about the ‘ND’ designation and other competing designations that non-regulated health care practitioners use, such as ‘nd’, ‘naturopath’, and ‘naturotherapist’.

46 www.ihpmagazine.com l September 2013

clinic profile

designations that non-regulated health care practitioners use, such as ‘nd’, ‘naturopath’, and ‘naturotherapist’. Many health plans cover services by nonregulated practitioners. One concern for the NDs is that many people assume they can’t afford naturopathic services. Another concern the practitioners have is that patients sometimes think that because they are seeing a medical doctor, seeing an ND may be counterproductive. The medical doctors can also perpetuate this idea because they may have had a bad experience with an unregulated practitioner. To remedy this, the clinic does a lot of community outreach work. They send letters to MPs and they try to work with local MDs by initiating and maintaining communication. A lot of education also occurs within the community. Both NDs write articles for local papers and send out monthly newsletters to their mailing list. Dr. Blake believes that by offering IV therapy, it has helped expand the clinic’s reach and credibility. Legislation is a big challenge and is a hot topic at provincial meetings. The largest obstacle faced by Naturopathic Doctors is the low number of practitioners. Unfortunately, this is a self-perpetuating problem. Because the province is unregulated, fewer NDs may want to practice there. In turn, because there are not a lot of NDs practicing, it becomes difficult to justify regulation! However, Dr. Blake has seen a large shift over the last several years. The public is more educated and the number of NDs has doubled provincially over the last 6 years. In an effort to promote awareness, the team has been actively involved in many wellness and health expos that occur in the area and have hosted successful networking events for health care practitioners.

The clinic hosts health programs and workshops for the public in an effort to continue integrating into the healthcare system.

Future plans for the clinic include expanding the team. They are actively seeking other practitioners who would fit well within their integrative model. They would especially like to find a health care practitioner that is linked to the conventional system, such as a Nurse Practitioner or an MD. The clinic hosts health programs and workshops for the public in an effort to continue integrating into the healthcare system. They are also looking forward to implementing a community acupuncture program, whereby multiple

acupuncture treatments could occur simultaneously. IHP would like to thank The Pear Tree Clinic for allowing us to showcase their accomplishments. ■

The Pear Tree Clinic 1067 Champlain St, Dieppe NB Phone: 506-857-1300 Fax: 506-853-3046 http://www.thepeartreeclinic.info

September 2013 l www.ihpmagazine.com 47

Introducing...

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A novel formula with anxiolytic activity • Bioactive decapeptide Lactium® with specific binding to GABA (A-1) receptors • Appropriate receptor binding without the side effects of drowsiness, memory loss, tolerance or addiction • Re-establishes the HPA feedback loop by increasing the sensitivity of the hypothalamus to cortisol • Decreases cortisol and CRH during chronic stress

Unregulated elevated levels of cortisol impair stage four delta wave sleep, destabilize mast cells, inhibit digestive enzyme production and increases endothelin and LDL levels. All of these effects contribute to increased cardiovascular disease, allergies, IBS and IBD. Balancing the hypothalamic-pituitary axis by re-establishing appropriate sensitivity within the feedback loop assists in mitigating these effects and normalizing cortisol levels. VISIT US @ DOUGLASLABS.CA OR CALL TOLL FREE @ 866.856.9954

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Anxiolytic effect reducing Mental and Physical Stress DESCRIPTION Sereniten Plus is a combination of Lactium®, L-Theanine and Vitamin D to support the HPA axis and feedback loop for stress management and cortisol regulation. FUNCTIONS The neurochemical and hormonal reactions to stress are regulated through the Hypothalamic-Pituitary-Adrenal axis (HPA axis) designed for acute stressors that resolve rapidly. Present day chronic, low-grade stress results in the continual release of CRH (Corticotropin Releasing Hormone) from the hypothalamus. This chronic secretion causes dysfunction in the HPA axis, desensitizing the hypothalamic and pituitary receptors to negative feedback from adrenaline, noradrenalin and particularly, cortisol. Loss of negative feedback within the neuro-hormonal system results in a multitude of health issues. It increases the production of ADH, aldosterone, and angiotensin increasing vascular vasoconstriction and sodium retention. It increases C-reactive protein and endothelin, promoting atherosclerosis and inflammation. It directly increases LDL production as well as glucocorticoid and mineralcorticoid release, further increasing cardiac risk. When the negative feedback loop within the HPA-axis is disrupted, chronic hormonal secretion becomes “normal” for that individual. In this state, they either fail to recognize they are stressed, or they may experience exaggerated emotional and physical response to every stressor including intolerance to noise or light, or feeling overwhelmed by simple tasks. Stress affects so many aspect of health that is becoming crucial to rebalance the HPA-axis. Lactium®, a bioactive decapeptide, alpha-1 sequence isolated from milk is effective in not only decreasing glucocorticoid secretion but will assist in rebalancing the HPA pathway. Lactium® works at three areas of the HPA-axis: 1) Lactium® binds specifically to the BZD site of the GABA-A receptor and does NOT bind to the PBR site of the GABA-A receptor responsible for the sedating effects seen with benzodiazepines. 2) Lactium® increases the sensitivity of the hypothalamus to cortisol, re-establishing receptor sensitivity feedback within the HPA-axis. It reduces the amount of CRH produced in response to stress. 3) Lactium® decreases the amount of cortisol released by the adrenal glands during acute and chronic stress. Studies in humans using alpha-S1-casein hydrolysate have resulted in anxiolytic-like effects, without side effects. Results showed a significant decrease in plasma cortisol throughout the combined stress tests and stable heart rate in the treatment group but not in the placebo group. Another study showed after 30 days of treatment a reduction in stress related symptoms including digestion, cardiovascular, intellectual, emotional, and social problems. L-Theanine is a unique amino acid derived from tea providing relaxation support without drowsiness. L-Theanine has been shown to increase alpha-wave production, an observed pattern considered to be an index of relaxation. Vitamin D has been included for additional support in reducing inflammation and supporting immune function. INDICATIONS Sereniten Plus is for individuals wanting to support their response to stress and reestablish HPA-axis to stress. FORMULA 201348 Each capsules contains: Casein decapeptide (milk)/ casein decapeptide (lait) (Lactium®) . . . . . . . . . . . . . . . . . . 175mg L-Theanine (Suntheanine®) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50mg Vitamin D3/Vitamine D3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100IU

SUGGESTED USE Adults take 1 capsule daily or as directed by your health care professional. Characterization of α-casozepine, a tryptic peptide from bovine αs1-casein with benzodiazepine-like activity. Laurent Miclo, Emmanuel Perrin. The FASEB Journal June 2001 De Saint-Hilaire,Z; et al. Effects of Bovine αs1-Casein Tryptic Hydrolysate (CTH) on Sleep Disorder in Japanese General Population. The Open Sleep Journal, 2009,2,26-32 Kim, JH; Desor,D; et al. Efficacy of αs1-casein hydrolysate on stress-related symptoms in women. European Journal of Clinical Nutrition (2006),1-6 Messaoudi,M; et al. Effects of tryptic hydrolysate from bovine milk αs1-casein on hemodynamic responses in healthy human volunteers facings successive mental and physical stress situations. Eur J Nutr (2004,)534-537 VISIT US @ DOUGLASLABS.CA OR CALL TOLL FREE @ 866.856.9954

Announcing

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Health Innovation Forum November 12–14, 2013 MaRS Discovery District, Toronto, ON www.HealthInnovationForum.com Solving multifaceted problems in health innovation requires thinking and system-wide cooperation New w Dynamics in Health is a unique, provocative cross-disciplinary program that oﬀers plenary, big-picture and highly creative and ﬂexible concurrent sessions that enable joint thinking and problem solving.

Take the opportunity to connect and collaborate with others in the system Attendees will network with other inﬂuential healthcare professionals who can provide fresh perspectives and oﬀer solutions around health innovation management and partnerships.

Delve into healthcare systems innovation and how it enables the adoption of new approaches and technologies • Breaking silos • Aligning incentives • E-enabling healthcare • Personalizing medicine

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• CEOs, CFOs, CMOs, COOs, CTOs • Presidents, Vice Presidents, Directors • VCs, Investors • HR & Supply Chain Managers • • Medical OR, ER Directors and Clinicians • Government Bodies/NGO and Universities • For More Information & Registration: Call: 416-512-3451 • Email: LifeSciences@informacanada.com • Website: www.HealthInnovationForum.com Produced by

PARTNERS

INCORPORATING:

The Journal of

Integrated Healthcare

Practitioners 1 2 3 CE

1 2

Bolton Naturopathic Clinic, Bolton, Ontario

Vitamin E

Obstacles and Opportunities in Cancer Prevention and Treatment by Elizabeth Stavros, ND, Amy Kroekes, ND, and Akbar Khan, MD

Medicor Cancer Centre, Toronto, Ontario

A Panacea for Human Disease by Philip Rouchotas, MSc, ND, and Heidi Fritz, MA, ND

N igella sativa

Iron & Diabetes A review

by William R Ware, PhD Emeritus Professor, Faculty of Science, University of Western Ontario

CE p82 Mushrooms in Cancer Care Evidence review

by Christopher Habib, ND and Mark Fontes, ND

Mahaya Forest Hill, Toronto, Ontario

September 2013 l www.ihpmagazine.com 51

editor’s letter

Naturopathy Act Nears Proclamation

he Naturopathy Act, that will govern the practice of naturopathic medicine in Ontario moving forward, has entered the 60- day period of public consultation, inching closer and closer to proclamation. Having the privilege of participating in the process as an OAND representative has taught me many lessons; initially frustrated by the redundancy of the process, one recognizes the value of redundancy when establishing law. My new frustration, however, resides in the uncertainty of political process… So many aspects of the Naturopathy Act, absolutely key and crucial to the ability of ND’s to maintain their current provision of care to patients, remain threatened under the currently proposed Act. Verbal, and even written assurances are provided, that the intention is to provide continuity in the care presently offered by ND’s. Yet with one stroke of the pen key features of care provided by ND’s could vanish. It seems we are left with few choices? Lobby key political stakeholders to ensure they understand the importance of the requests being made by the profession? Thereafter, wait and hope for the best… The uncertainty feels crippling. We strongly encourage every ND in the province to invest the time to study the proposed Act, and provide your feedback. The deadline for such feedback is fast approaching – Sept 10, 2013. Please, get involved! William R Ware, PhD, is a frequent contributor to IHP. This issue delivers what may be his finest contribution to the publication thus far; a compelling review of the role of iron stores in diabetes, suggesting that reducing iron stores may reduce diabetes risk in high- risk individuals, and improve glucose management in those with diabetes. Dr’s Stavros, Kroeker, and Khan provide an interesting review of vitamin E in cancer prevention and treatment. Dr Fritz and myself review an herbal medicine seemingly famous among elder ND’s, yet poorly known among more recent grads; Nigella sativa. The continuing education article of the issue reviews application of several medicinal mushrooms.

Best Regards, Philip Rouchotas, MSc, ND Editor-in-Chief We invite questions or comments. philip@ihpmagazine.com

52 www.ihpmagazine.com l September 2013

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Integrated Healthcare

President | Olivier Felicio (416) 203-7900 ext. 6107 CEO | Cory Boiselle (416) 203-7900 ext. 6114 Controller & Operations | Melanie Seth CMO | Zinnia Crawford (416) 203-7900 ext. 6135 Advertising Information Sanjiv Jagota | Tel: (416) 203-7900 ext 6125 Email: sanjiv@ihpmagazine.com Jeff Yamaguchi | Tel: (416) 203-7900 ext 6122 Email: jeff@gorgmgo.com Jason Cawley | Tel: (416) 203-7900 ext 6134 Email: jason@gorgmgo.com Erin Poredos | Tel: (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

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September 2013 l www.ihpmagazine.com 47

Nutritional Fundamentals for Health I3C SAP

Targeted nutraceutical therapy for the prevention and treatment of estrogen-dependent cancers

Indole-3-carbinol (I3C) is a phytochemical derived in high concentrations from the Brassica family of vegetables, including broccoli, cauliflower, Brussels sprouts, and cabbage. I3C and its derivative compounds have been shown to exert anticancer mechanisms in the human body. I3C has been shown to exhibit direct antiestrogenic activity via competitive inhibition of estrogen receptors; upregulate the cytochrome P450 isoenzymes CYP1A1, CYP1A2 and CYP1B1, thereby increasing estrogen metabolism; shift estrogen metabolism away from the more proliferative (16-OHE1) towards the more protective (2-OHE1) estrogen species; induce cancer cell apoptosis via NF-κB pathways; inhibit cancer cell growth at the G1 stage; and increase the expression of p21, p27 and p53 tumor suppressors. The use of I3C for the prevention and treatment of breast, endometrial, colon, and prostate cancers as well as for the treatment of Herpes simplex virus (HSV) and human papillomavirus (HPV), including cervical dysplasia and cervical cancer, has been studied in depth in both animals and humans with favorable results. Each NON-GMO vegetable capsule contains:

ACTIVE INGREDIENTS

Indole-3-carbinol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 mg

Contains no: Preservatives, artificial flavor or color, sugar, dairy, wheat, gluten, corn, soy or yeast. I3C SAP contains 60 capsules per bottle.

DOSAGE

Adults: Take 1–4 capsules daily with meals or as directed by your health care practitioner.

INDICATIONS

ɶ I3C may be used in the prevention and treatment of estrogendependent breast, colon, endometrial, cervical and prostate cancers. ɶ I3C may be used in the prevention and treatment of HSV and HPV infections. ɶ I3C may be used to support healthy estrogen and androgen metabolism.

TOXICITY

No side effects or adverse events have been reported at regular therapeutic dosages. In doses exceeding 800 mg/d, oral administration of I3C may cause reversible symptoms of tremor, nausea, and imbalance or unsteadiness.

PURITY, CLEANLINESS AND STABILITY

Third-party testing is performed on finished product to ensure that I3C SAP is free of heavy metals, pesticides, volatile organics and other impurities.

Scientific Advisory Panel (SAP): adding nutraceutical research to achieve optimum health

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

Nutritional Fundamentals for Health I3C SAP Product Monograph

BACKGROUND AND PHARMACOKINETICS

Indole-3-carbinol (I3C) is a naturally occurring phytonutrient present in high quantities in cruciferous vegetables from the Brassica genus, including broccoli, cauliflower, Brussels sprouts, and cabbage. I3C is a highly researched phytonutrient, particularly in terms of its ability to modulate the effects of estrogen and its implications in estrogensensitive cancers via various mechanisms of action.(1, 2, 3) After human ingestion in the presence of an acidic environment, I3C is hydrolyzed mainly into the dimer, 3,3′-diindolylmethane (DIM), amongst other metabolites. Both I3C and DIM, in addition to the more minor metabolites of I3C, are biologically active and exert a number of health-promoting effects that may have primarily antiestrogenic and antiandrogenic effects, which may be harnessed for the prevention and treatment of various cancers.(1, 2, 3) Both I3C and DIM are rapidly absorbed into human plasma and tissues within one hour of dosage and eliminated primarily via the urine initially, and also via fecal route after 40 h of continuous therapy. I3C metabolites demonstrate a serum half-life greater than 48 h following one-week continuous oral administration.(1, 2)

BREAST CANCER AND ANTIESTROGEN

Increased estrogen levels and exposure to estrogens are well-known to be risk factors in the development of breast cancer and other estrogensensitive cancers. I3C and its metabolites exhibit antiestrogenic activity via competitive inhibition of estrogen receptors. DIM has been specifically demonstrated to selectively bind estrogen receptors and act as an estrogen antagonist.(1, 2) Through direct inhibition of estrogen receptors and other antiestrogenic effects, I3C has been rigorously implicated in the literature as a preventative and treatment for breast cancer, both in conjunction with and independent of tamoxifen and other conventional, pharmaceutical treatments.(1, 2, 3, 4, 5, 6)

HEPATOPROTECTION AND DETOXIFICATION

In addition to the direct competitive inhibition of estrogen receptors, I3C and its metabolites—specifically DIM and indolylcarbazole (ICZ)— induce the human cytochrome P450 isoenzymes CYP1A1, CYP1A2 and in Sprague-Dawley rats, CYP1B1/2. Through induction of these isoenzymes, I3C promotes Phase I and Phase II detoxification and exhibits hepatoprotective activity.(1, 2, 3, 4, 7, 8)

2:16-HYDROXYESTRONE RATIO

The metabolism of estradiol (E2) by hepatocytes results in the primary production of either 2-hydroxyestrone (2-OHE1) or 16-alphahydroxyestrone (16-OHE1). It is generally accepted that 16-OHE1 causes the proliferation of some breast cancer cell lines, while 2-OHE1 has a protective effect for breast cancers. A 2:1 urinary ratio appears to be optimal, while a 1:1 ratio has been associated with increased risk of breast cancers. The 2:16-hydroxyestrone ratio may therefore be considered a risk factor for breast cancer; supplementation of I3C has been demonstrated to increase this ratio.(1, 2, 3, 4, 8) In a study, upon I3C oral administration, urinary excretion levels of 2-OHE1 doubled, while 16-OHE1 levels decreased by 45%, demonstrating the ability of I3C to increase the 2:16-hydroxyestrone ratio.(9) These findings are echoed by results of a study that showed a 66% increase in urinary 2:16-hydroxyestrone ratio in response to oral I3C administration.(10)

ANTIPROLIFERATIVE AND APOPTOSIS-INDUCING

In vitro studies have shown I3C’s ability to inhibit breast-cancer cells’ ability to invade surrounding tissues via upregulation of tumor-suppressing genes PTEN and E-cadherin. p53, p21 and p27 are cyclin-dependent kinase inhibitors which control cell cycle progression; I3C is known to increase

For more information visit: www.nfh.ca

IHP 2013-08,09 (Women’s Health Symposium, Inositol SAP + Flora SAP, I3c SAP + monograph).indd 4

p21, p27 and p53 expression, thereby arresting tumor cell growth cycles in the G1 state. Additionally, incubation of human breast cancer cells with DIM has been found to stimulate apoptosis independent of p53 and downregulates NF-κB, inducing apoptosis in various cell lines, including myeloid, leukemia and breast cancer cells.(1, 3, 7, 8)

DNA-PROTECTIVE

BRCA1 and BRCA2 are human caretaker genes that repair breaks in DNA due to transcription error or mutation. Upregulation of both BRCA1 and BRCA2 by I3C oral supplementation is suggested to play a role in breast cancer prevention.(2, 6, 8)

PROSTATE CANCER AND ANTIANDROGEN

DIM inhibits dihydrotestosterone (DHT) stimulation of DNA synthesis and competitively inhibits androgen-receptor binding of DHT. I3C and DIM have both been independently shown to suppress proliferation of prostate cancer cells. As in studies focused on breast cancer, increased p21, 27 and p53 expression and downregulation of NF-κB have also been demonstrated in prostate cancer, leading to healthy cancer cell apoptosis.(2, 3, 7, 11, 12, 13, 14, 15) Furthermore, I3C & DIM have also been shown to decrease PSA levels 5-fold within 48 h via inhibition of PSA gene transcription.(14)

OTHER CLINICAL INDICATIONS

I3C and DIM have also been studied in the treatment and prevention of HSV, HPV, and cervical cancer, colon cancer, and endometrial cancer.(1, 3, 5)

DOSAGE, TOXICITY & CONTRAINDICATIONS

Optimal therapeutic dosage for I3C has been cited as 400 mg/d— equivalent to about that found in one-third of a head of cabbage.(1, 8, 10) No therapeutic advantage has been shown for the direct oral administration of DIM over I3C.(16) In fact, DIM administration alone has been shown to inhibit CYP1A1, CYP1A2 and CYP2B1/2; processes that would contradict the estrogen detoxification benefits shown by upstream I3C oral administration.(8) No adverse events or side effects are expected at a dose of 400 mg/d in humans, and I3C administration is generally well tolerated. Over 800 mg/d, symptoms including tremor, unsteadiness, nausea, and imbalance have been recorded. Observed side effects are reversible upon dose reduction or withdrawal and are not life threatening.(1, 16)

REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.

“Indole-3-carbinol – Monograph”, Alternative Medicine Review 10, No. 4 (2005): 337–342. Fan, S, et al. “BRCA1 and BRCA2 as molecular targets for phytochemicals indole-3-carbinol and genistein in breast and prostate cancer cells”, British Journal of Cancer 94, No. 3 (2006): 407–426. Aggarwal, B.B. and H. Ichikawa. “Molecular targets and anticancer potential of indole-3-carbinol and its derivatives”, Cell Cycle 4, No. 9 (2005): 1201–1215. Ashok, B.T., et al. “Abrogation of estrogen-mediated cellular and biochemical effects by indole-3-carbinol”, Nutritrion and Cancer 41, No. 1–2 (2001): 180–187. Auborn, K.J., et al. “Indole-3-carbinol is a negative regulator of estrogen”, The Journal of Nutrition 133, No. 7 (2003): 2470S–2475S. Meng, Q., et al. “Indole-3-carbinol is a negative regulator of estrogen receptor-alpha signaling in human tumor cells”, The Journal of Nutrition 130, No. 12 (2000): 2927–2931. Sarkar, F.H. and Y. Li. “Indole-3-carbinol and prostate cancer”, The Journal of Nutrition 134, No. 12 (2004): 3493S–3498S. Rogan, E.G. “The Natural chemopreventive compound indole-3-carbinol: State of the science”, In Vivo 20, No. 2 (2006): 221–228. Michnovicz, J.J., H. Adlercreutz, and H.L. Bradlow. “Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans”, Journal of the National Cancer Institute 89, No. 10 (1997): 718–723. Reed, G.A., et al. “A Phase I study of indole-3-carbinol in women: Tolerability and effects”, Cancer Epidemiology, Biomarkers & Prevention 14 (2005): 1953–1960. Nachshon-Kedmia, M., et al. “Indole-3-carbinol and 3,3′-diindolylmethane induce apoptosis in human prostate cancer cells”, Food and Chemical Toxicology 41, issue 6 (2003): 745–752. Chinni, S.R., et al. “Indole-3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells”, Oncogene 20, No. 23 (2001): 2927–2936. Zhang, J., et al. “Indole-3-carbinol induces a G1 cell cycle arrest and inhibits prostate-specific antigen production in human LNCaP prostate carcinoma cells”, Cancer 98, No. 11 (2003): 2511–2520. Hsu, J.C., et al. “Indole-3-carbinol inhibition of androgen receptor expression and downregulation of androgen responsiveness in human prostate cancer cells”, Carcinogenesis 26, No. 11 (2005): 1896–1904. Frydoonfar, H.R., D.R. McGrath, and A.D. Spigelman. “The effect of indole-3-carbinol and sulforaphane on a prostate cancer cell line”, ANZ Journal of Surgery 73, No. 3 (2003): 154–156. Minich, D.M. and J.S. Bland. “A review of the clinical efficacy and safety of cruciferous vegetable phytochemicals”, Nutrition Reviews 65, No. 6 (2007): 259–267.

2013-07-29 14:22:07

peer review

Peer Review Board Members Andrea Maxim, ND Healing Journey Naturopathic Clinic 25 Caithness St. W. Caledonia, Ontario N3W 1B7 andreamaximnd@gmail.com

Colin MacLeod, ND Alderney Chiropractic 164 Ochterloney St. Dartmouth, Nova Scotia B2Y 1E1 info@drcolinmacleod.com

Erin Psota, BSc, ND King West Village Medical Centre 626 King St West, Suite 201 Toronto, Ontario M5V 1M7 drpsota@gmail.com

Anthony Moscar, ND Mahaya Forest Hill 73 Warren Road, Suite 102 Toronto, Ontario M4V 2R9 anthonymoscar@gmail.com

Daniel Watters, BSc, ND Rosedale Wellness Centre 365 Bloor St East Toronto, Ontario M4W 3L4 dwatters@rosedalewellness.com

Faryal Luhar, ND Healthwise Wellness 4250 Weston Rd Toronto, Ontario M9L 1W9 ndluhar@hotmail.com

Aoife Earls, MSc, ND Trafalgar Ridge Chiropractic and Acupuncture 2387 Trafalgar Road, Unit 7A Oakville, Ontario L6H 6K7 aearlsnd@gmail.com Berchman Wong, ND 718 - 33 Canniff St Toronto, Ontario M6K 3M5 berchman.nd@gmail.com Betty Rozendaal, BES, MA, ND Thornhill Naturopathic Health Clinic 12A Centre Street Thornhill, Ontario L4J 1E9 drbetty@thornhillnaturopathic.ca Brock McGregor, ND McGregor Naturopathic 220 St Clair Street Chatham, Ontario N7L 3J7 drbrock@mcgregornd.com Carol Morley, ND Zawada Health 201 City Centre Drive, Suite 404 Mississauga, Ontario L5B 2G6 info@zawadahealth.com Claire Girgis, ND Zawada Health 201 City Centre Drive, Suite 404 Mississauga, Ontario L5B 2G6 claire@zawadahealth.com

56 www.ihpmagazine.com l September 2013

David W Lescheid, BSc, PhD, ND Lichtentaler Strasse 48 76530 Baden-Baden, Germany 20davidl20@gmail.com David Miller, BSc, ND 662 Gustavus Street Port Elgin, Ontario N0H2C0 drdavend@yahoo.ca Denisa Maruyama, ND Kona Wellness Center for Integrative Medicine 74-5565 Luhia Street Suite C-2 Kailua-Kona, Hawaii drmaruyama@konawellness.com Elaine Lewis, HBSc, ND Back to Play Chiropractic 592 Rathburn Road West Mississauga, Ontario L5B 3A4 elewis@ccnm.edu Elizabeth Cherevaty, BSc, ND Norfolk Chiropractic Wellness Centre 86 Norfolk Street, Suite 101 Guelph, Ontario N1H 4J2 elizabeth.cherevaty@gmail.com Erin Balodis, BSc, MSc, ND Kingswood Chiropractic Health Centre 1210 Hammonds Plains Road Hammonds Plains Nova Scotia B4B 1B4 erinbalodis@gmail.com

Heidi Fritz, MA, ND Canadian College of Naturopathic Medicine 1255 Sheppard Ave East Toronto, Ontario M2K 1E2 hfritz@ccnm.edu Isaac Eliaz, MD, MS, LAc Amitabha Medical Clinic & Healing Center 7064 Corline Ct #A Sebastopol, California 95472-4528 ieliaz@sonic.net Jacob Scheer, DC, ND, MHSc 2100 Finch Ave. W. #206 North York, Ontario M3N 2Z9 Jacob.Scheer@utoronto.ca Jiselle Griffith, BSc, ND The Health Hub Integrated Clinic 35 Hayden St, Suite 109 Toronto, Ontario M4Y 3C3 jiselle@healthhubclinic.com Jordan Robertson, BSc, ND Lakeshore Clinic 2159 Lakeshore Road Burlington, Ontario L7R 1A5 jordanrobertsonnd@gmail.com Judah Bunin, BSc, MSc, ND, DrAc Fredericton Naturopathic Clinic 10-150 Cliffe St Fredericton, New Brunswick E3A0A1 frednatclin@yahoo.ca

peer review

Karam Bains, BSc, ND Inside Out Wellness 3650 Langstaff Road, Unit 12 Woodbridge, Ontario karam@elixirhealth.ca

Meghan MacKinnon, ND Armata Health Centre 126 Welling St. W, Unit 201B Aurora, Ontario L4G 2N9 drmeg.nd@gmail.com

Shawna Clark, ND Forces of Nature Naturopathic Clinic 2447 1/2 Yonge St Toronto, Ontario M4P 2E7 info@shawnaclarknd.com

Kate Whimster, ND Kew Beach Naturopathic Clinic 2010 Queen Street East, 2nd floor Toronto, Ontario kwhimster@wavelengthwellness.com

Melanie DesChatelets, BSc, ND True Health Studio 200-4255 Arbutus St Vancouver, British Columbia V6J 4R1 melanie@drdeschat.com

Stephanie Swinkles, DDS Elmsdale Dental Clinic 4-269 Highway 214 Elmsdale, Nova Scotia N2S 1K1 steph_moroze@hotmail.com

Kelly Brown, BSc, ND Clinic One 286 McDermont Avenue Winnipeg, Manitoba R3B 1H6 drkbrownnd@gmail.com Leigh Arseneau, ND Centre for Advanced Medicine 670 Taunton Rd East Whitby, Ontario L1R 0K6 info@advancedmedicine.ca Lindsay Bast, BSc, ND Greenwood Wellness Clinic PO Box 189 1400 Greenwood Hill Rd. Wellesley, Ontario N0B 2T0 lindsay.bast@greenwoodclinic.ca Louise Wilson, BSc, ND 320 Queen St S Bolton, Ontario L7E 4Z9 dr.louisewilsonnd@gmail.com Maria Shapoval, ND Canadian College of Naturopathic Medicine 1255 Sheppard Ave East Toronto, Ontario M2K 1E2 mshapoval@ccnm.edu Makoto Trotter, ND Zen-tai Wellness Centre 120 Carlton Street, Suite 302 Toronto, Ontario M5A 4K2 makoto@zen-tai.com Mandana Edalati, BA, ND Wellness Naturopathic Centre Suite 213-1940 Lonsdale Ave North Vancouver, British Columbia V7M 2K2 dredalati@gmail.com

Misa Kawasaki, BSc, ND Meridian Wellness 13085 Yonge Street, Suite 205 Richmond Hill, Ontario L4E 3S8 drkawasaki@meridianwellness.ca

Susan Coulter, BSc, ND Roots of Health 2-497 Laurier Ave Milton, Ontario L9T 3K8 scoulter@rootsofhealth.ca

Nicole Egenberger, BSc, ND Remede Naturopathics 214 Sullivan Street Suite 3B New York, New York 10012 info@remedenaturopathics.com

Sylvi Martin, BScN, ND Fusion Chiropractic and Integrative Health 735 Danforth Avenue Toronto, Ontario M4J 1L2 info@fusionchiropractic.ca

Nicole Sandilands, ND Durham Natural Health Centre 1550 Kingston Rd, Suite 318 Pickering, Ontario L1V 1C3 info@dnhc.ca

Tanya Lee, BSc, ND The Health Centre of Milton 400 Main St East Suite 210 Milton, Ontario L9T 1P7 tanyalee.nd@gmail.com

Raza Shah, BSc, ND St. Jacobs Naturopathic 1-9 Parkside Drive St. Jacobs, Ontario N0B 2NO stjacobs.nd@gmail.com

Terry Vanderheyden, ND Bayside Naturopathic Medicine 118 Bay Street Barryâ&#x20AC;&#x2122;s Bay, Ontario KOJ 1B0 doctrv@gmail.com

Rochelle Wilcox, BA, ND Living Well Integrative Health Centre 2176 Windsor Street Halifax, Nova Scotia B3K 5B6 drwilcox@balancehealthcentre.ca

Theresa Jahn, BSc, ND Living Well Integrative Health Centre 2176 Windsor Street Halifax, Nova Scotia B3K 5B6 info@theresajahn.com

Sarah Vadeboncoeur, ND Ottawa Integrative Health Centre 1129 Carling Ave Ottawa, Ontario K1Y 4G6 sarahmvadeboncoeur@gmail.com Scott Clack, ND Touchstone Naturopathic Centre 950 Southdown Rd, Unit B5 Mississauga, Ontario L5J 2Y4 sclack.nd@touchstonecentre.com September 2013 l www.ihpmagazine.com 57

Discover Calm Within the Storm

A swirling storm of worry and doubt leaves many patients struggling with occasional anxiety and restlessness. Lavela WS 1265™ contains Silexan™, an exclusive, clinically studied, lavender essential oil. Lavela WS 1265 has been shown to relieve occasional anxiety and promote relaxation in peer-reviewed, controlled trials.1,2 Lavela WS 1265™ - An Anxiously Awaited Solution - Clinically documented to relieve occasional anxiety - Convenient, once-daily dosing - Non-habit-forming, non-sedating relief

Silexan™ is a trademark of Dr. Willmar Schwabe 1. Woelk H, Schläfke S. A multi-center, double-blind, randomized study of the Lavender oil preparation Silexan in comparison to [drug name] for generalized anxiety disorder. Phytomedicine 2010;17:94–9. 2. Kasper S, Gastpar M, Müller WE, et al. Silexan, an orally administered Lavandula oil preparation, is eﬀective in the treatment of ‘subsyndromal’ anxiety disorder: a randomized, double-blind, placebo controlled trial. Int Clin Psychopharmacol 2010;25:277–87.

1.800.644.3211 • www.integrativeinc.com

editorial board

IHP Editorial Board Members The purpose of our Editorial Board is to help guide the direction of the publication, in a manner that A) improves academic quality and rigor, B) exerts a positive impact on patient outcomes, C) contributes to knowledge of integrative healthcare, and D) showcases evolving trends in the healthcare industry. We have appointed a dynamic mix of individuals representing integrative MD’s, profession-leading ND’s, and members of academia. This unique blend of minds comes together and has already provided

insight that is actively shaping the manner in which IHP is compiled. Our goal remains successful listing with the PubMed database of scientific literature, and the contributions of this incredible team are an important step in the right direction. IHP is grateful to the donation of time and expertise made by these incredible professionals. The best way we can think of honouring their contribution is to effectively implement their suggestions and thus continuously elevate the quality of delivery of this publication.

Jason Boxtart, ND

Dr Boxtart is currently serving as Chair to the Board of Directors for the Canadian Association of Naturopathic Doctors, the national association of naturopathic medicine in Canada. In that position he also chairs the Canadian Naturopathic Coordinating Council, the national stakeholder group in Canada. He also is a Board member of the Canadian Naturopathic Foundation, the national naturopathic charity. For the last eight years Dr Boxtart has held a Faculty of Medicine post with the University of Northern British Columbia. Jason, and his wife Dr Cher Boomhower, ND, share the role of Medical Director for the Northern Center for Integrative Medicine, a multi-practitioner clinic in Prince George, BC.

Ben Boucher, MD

Dr Boucher is a Nova Scotian of Acadian-Metis heritage who spent his early years in Havre Boucher, NS. He attended St. Francis Xavier University where he graduated in 1973. In 1978, he obtained a Doctor of Medicine degree from Dalhousie University, NS. Since 1979, he has practiced rural medicine in Cape Breton, NS. Although he has a very large general practice, he has special interests in chelation therapy and metal toxicity. In the past three years, he has been recognizing and treating vector- transmitted infections. Dr Ben does his best to help patients by following Sir William Osler’s approach whereby if one listens long enough to a patient, together the answer will be found.

60 www.ihpmagazine.com l September 2013

editorial board

Pardeep Nijhawan, MD, FRCP(C), FACG

Dr Nijhawan completed his medical school training at the University of Ottawa and proceeded to complete an internal medicine internship at Yale-Norwalk, CT. He completed his internal medicine residency and Gastroenterology and Hepatology fellowship at the Mayo Clinic in Rochester, MN. There he was awarded the Calgary fellowship for outstanding achievements. He is a member of the Royal College of Physicians and Surgeons of Canada, American Board of Gastroenterology, and American Board of Internal Medicine. In 2003, Dr Nijhawan established the Digestive Health Clinic to help bring leading edge technology to Canada. He specializes in therapeutic endoscopy, irritable bowel and celiac disease.

Gurdev Parmar, ND, FABNO

Dr Parmar is a respected leader in the field of Integrative Oncology. He and his wife, Dr Karen Parmar, launched the Integrated Health Clinic in 2000 and have since facilitated its growth to become one of the largest and most successful integrated health care facilities in Canada. Dr Parmar was the first Canadian naturopathic physician to hold a fellowship to the American Board of Naturopathic Oncology (FABNO), a board certification as a cancer specialist. Dr Parmar has been a consulting physician at the Lions Gate Hospital chemotherapy clinic since 2008, creating the first Integrative Oncology service in any chemotherapy hospital in the country.

Kristy Prouse, MD, FRCSC

Dr Prouse has practiced as an Obstetrician/Gynaecologist for over 10 years and currently holds the position of assistant professor at the University of Toronto and the Northern Ontario School of Medicine. Dr Prouse completed her medical degree at Queen’s University and residency training at the University of Calgary. Additionally, Dr Prouse has trained in bio-identical hormone replacement therapy and anti-aging and regenerative medicine through the University of Southern Florida-College of Medicine. She is the Founder and Chief Medical Officer at the Institute for Hormonal Health, an integrative medical practice in Oakville, Ontario that focuses on hormonal imbalances in both women and men. Kristy completed her residency training at the University of Calgary, while obtaining her medical degree from Queen’s.

Dugald Seely, ND, MSc

Dr Seely is a naturopathic doctor and director of research at the Canadian College of Naturopathic Medicine (CCNM). Dugald completed his masters of science in cancer research from the University of Toronto with a focus on interactions between chemotherapy and natural health products. In his current role as director of research, Dugald is the principal investigator for a number of clinical trials, and is actively pursuing relevant synthesis research in the production of systematic reviews and meta-analyses. Ongoing projects include three multi-centred randomized clinical trials and a comprehensive CIHR synthesis review of natural health products used for cancer. Dugald is currently a member of Health Canada’s Expert Advisory Committee for the Vigilance of Health Products and is a peer reviewer for the Canadian Adverse Reaction Newsletter.

September 2013 l www.ihpmagazine.com 61

How to Read a Fish Oil Label

Don’t stop at 1,000 mg of fish oils — LOOK FURTHER! ✓ NPN number

NPN#80005548

Look for the NPN number to be sure the product is registered and has been approved by Health Canada.

• Carlson Super Omega-3 Fish Oil helps support cognitive health and brain function. / Sup u er Oméga-3 huililile up le de d pois i son de is d Ca C rrlllsson contr tririb tr ibue à lla santé t té cognitititve v et ou aux u ux fo f nctititio ions céré r bra ré r le ra l s. u er up • Carlson Super Omega-3 Fish Oil helps maintain cardiovascular health. / Sup rrd e. t card té diio di ovvascula l irirre la Oméga-3 huililile le de d pois iisson d de Ca C rlrls lson aid iid de à main de i te in t niriri lla santé Each soft gel contains: Medicinal Ingredient:

ttiie ient: t t: Chaque gélule l conti le Ingré r d ré diiie ent médi d diiic ciinal:

Fish Oil 1000 mg {[Anchovy (En E gra En r ulililid ra iddaae - Whole) and Sardine (Cl C Clup u eid ida id dae - Whole)] EPA [Eicosapentaenoic Acid] 300 mg DHA [Docosahexaenoic Acid]} 200 mg

Huiliille le dde Pois i son is {{[[A [Anchois i (E is (En Engra r ulilliid ra ida dae - EEnttiie ierr) et Sa S rd rddiin ine (C (Cl Clup u eid iddaae - En id E titie ier) r] e e] AEP E [[Acid EP iddee EEiic id icosapenta t éénoique] ta ]} ADH [A [ cid iddee Docosahex id exa ex xaén é oique] e]} e]

✓ DHA and EPA Look for substantial amounts of DHA and EPA which support cardiovascular and cognitive health.

Non-medicinal Ingredients: Gelatin, glycerin, water, tocopherols. / Ingré r d ré diie ients t non médi ts diicciinaux di ux: ux x: Géla l ti la tin ine, gly lyc ly ycéri riin ri ne, eau, to t cop o héro op r ls ro l .

✓ Serving Size

Directions: Adults: Take 1 softgel capsule twice per day with meals. / M Mod de d’e ’ mp ’e m lo l i: i Adu d dulltte tes: Pr Pre rendr drre dr e 1 gélu l le lu l de d u ux ffois i par jo j ur ave v cd ve des rre epas. ep Preservative-free. Cholesterol-free. / Sans agents t de ts d conserva v titio va ion. Sans chole l sté le t ro té r l. Do not purchase if safety seal is broken or missing / Ne pas achete t r si le te l sceau sécuri rrita t ir ire re est bri ris ri isé ou manquant. tt.

Check the number of soft gels/capsules in the dosage. (Some products with higher potencies listed on the label may require taking multiple soft gels).

- PURITY GUARANTEED / PUR U ETÉ UR T GA TÉ G RA R NTI T TIIE IE This product is regularly tested (using AOAC international protocols) for freshness, potency and purity by an independent, FDA-registered laboratory rry and has been determined to be fresh, fully-potent and free from detrimental levels of mercury r , cadmium, lead, PCB’s and 28 other contaminants. / Ce ry C pro r d ro du u uiitit fa f iit ré rég égul ulliiè ièrrement l’o ’ bj ’o bje jet de d contr trô tr rôlles (a ( u moy oyye oy en d des pro r to ro t cole l s iinte le t rn r atititio ionaux u de ux d l’A ’ OA ’A O C C, Associ cia ci iatitiio on of Offfffffiiiccciiia al Analy llyyt yttiic ica cal C emis Ch iists ts) s) afiffiiin n d’e ’ n vé ’e v ririfififie ier la l ffrra raîîccch heur, r la r, l pui uis ui issance et la l pure rretté par un u la l bora r to ra t irire re iindé dép épenda d nt enre da rre e eg g giis istr tré ré aup u rè up r s du d Secr cré cr réta t riria iat amérirriiicca cain i aux u pro ux r du ro du uiiitttss alililim imenta ttairire res et pharm r aceutititiq rm iques (F (FD FDA DA A)) et a été tté ju jug ugé comme éta t nt ta fra fr rais is, s, ple l iinement effffffific le icca ace et sans d de e eg gré gr rés nui uis ui isib i le l s de d merc r ure rc r , ca re c dm d iu iu um m, plo l mb, lo b BPC et 2 b, 28 autr ttrrre es conta t min ta i ants in t. ts

✓ Testing Make sure the product is tested for freshness, potency and purity.

Manufactured for / Fa F bri rriiq iqué pour: r r: J.R. Carlson Laboratories, Inc., 888-234-5656 • www.carlsonlabs.com Arlington Heights, IL 60004-1985, USA / ÉÉ U. Imported by / Imp m ort mp rté rt té par: r r: MMP Enterprises Ltd., 1520 Creditstone Road Concord, ON L4K5W2

Be sure it has been tested for contaminants and heavy metals.

POTENCY AND QUALITY GUARANTEED G RA GA R NTI TIIEE DE PUI TI U UIIS ISSA S NCE C ET DE QUA CE U LITÉ UA T TÉ

The leader in Norwegian Fish Oils 888-234-5656 | www.carlsonlabs.com

IHP MONOGRAPH C A R L S O N : T H E V E RY F I N E S T F I S H O I L Carlson The Very FinestFish Oil provides a high quality, pure source of the omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs) EPA and DHA,derived from 100% Norwegian sources. Eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) are well known for their anti-inflammatory effects, exerted through competitive inhibition of the cyclooxygenase (COX-2) and lipooxygenase (LOX) enzymes (Lim 2009); and have been the subject of extensive scientific research for their benefit on cardiovascular health, mood and cognitive function, as well as a broad range of inflammatory conditions such as arthritis, inflammatory bowel disease (IBD), and liver disease (Wall 2010). Arguably the most important of these is the effect of EPA and DHA on cardiovascular health. Fish oil has been reproducibly demonstrated to reduce the risk of sudden coronary death, as well as non-fatal cardiac events with a large magnitude of effect, in both patients recovering from a heart attack (secondary prevention) and in patients with no history of cardiovascular events (primary prevention) (Marchioli 2002, Yokoyama 2007). The Gissi Prevenzione trial, conducted in over 11 thousand patients, found that 1000mg daily of combined EPA+DHA for 3.5 years in addition to standard pharmaceutical therapy reduced the risk of sudden coronary death by 45% (RR 0.55, 95%CI 0.39–0.77), and reduced risk of all cause death by 21% (RR 0.79, 95% CI 0.66–0.93) (No authors 1999, Marchioli 2002). Other scientists have suggested that even doses as low as 250mg per day of combined EPA+DHA may be sufficient to obtain some level of benefit (Mozaffarian 2006).

Higher doses of EPA+DHA are required in order to impact cholesterol, however, in particular the triglyceride (TG) component. A dose of 2000 to 4000mg of combined EPA+DHA reduces fasting TG 25-30% and increases HDL cholesterol 1-3% (Harris 1997). Through this mechanism, higher doses of fish oil yield added benefits to cardiovascular health. EPA has also been shown to reduce the inflammatory activity of atherosclerotic plaques when incorporated into these arterial lesions, thus slowing their progression (Cawood 2010). In addition to effects on cardiovascular health, supplementation with EPA+DHA has been shown to improve several chronic inflammatory conditions, including liver damage in non-alcoholic steatohepatitis (Tanaka 2008); clinical improvement of ulcerative colitis and improvement of joint pain, and plasma markers of inflammation in patients with IBD (Aslan 1992, Brunborg 2008); and symptomatic improvements in both autoimmune arthritis (Madland 2006) and osteoarthritis (Gruenwald 2009). Carlson guarantees the quality and potency of their fish oil. The Very Finest Fish Oil is regularly subjected to rigorous independent testing by an FDA-registered laboratory for the mercury, cadmium, lead, PCBs, and 28 other contaminants. Carlson fish oil is both sourced from and bottled in Norway to provide maximum purity and product freshness.

References Aslan A, Triadafilopoulos G. Fish oil fatty acid supplementation in active ulcerative colitis: a double-blind, placebo-controlled, crossover study. Am J Gastroenterol. 1992 Apr;87(4):432-7. Brunborg LA, Madland TM, Lind RA, Arslan G, Berstad A, Frøyland L. Effects of short-term oral administration of dietary marine oils in patients with inflammatory bowel disease and joint pain: a pilot study comparing seal oil and cod liver oil. Clin Nutr. 2008 Aug;27(4):614-22. Cawood AL, Ding R, Napper FL, Young RH, Williams JA, Ward MJ, Gudmundsen O, Vige R, Payne SP, Ye S, Shearman CP, Gallagher PJ, Grimble RF, Calder PC. Eicosapentaenoic 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 Sep;26(9):858-71. Harris WS. n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997 May;65(5 Suppl):1645S-1654S. Lim K, Han C, Dai Y, Shen M, Wu T. Omega-3 polyunsaturated fatty acids inhibithepatocellular carcinoma cell growth through blocking beta-catenin andcyclooxygenase-2. Mol Cancer Ther. 2009 Nov;8(11):3046-55. Madland TM, Björkkjaer T, Brunborg LA, Fröyland L, Berstad A, Brun JG. Subjective improvement in patients with psoriatic arthritis after short-term oral treatment with seal oil. A pilot study with double blind comparison to soy oil. J Rheumatol. 2006 Feb;33(2):307-10.

Marchioli R, Barzi F, Bomba E, et al; GISSI-Prevenzione Investigators. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione. Circulation. 2002 Apr 23;105(16):1897-903. Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA. 2006 Oct 18;296(15):1885-99. No Authors. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet. 1999 Aug 7;354(9177):447-55. Tanaka N, Sano K, Horiuchi A, Tanaka E, Kiyosawa K, Aoyama T. Highly purified eicosapentaenoic acid treatment improves nonalcoholic steatohepatitis. J Clin Gastroenterol. 2008 Apr;42(4):413-8. Wall R, Ross RP, Fitzgerald GF, Stanton C. Fatty acids from fish: the antiinflammatory potential of long-chain omega-3 fatty acids. Nutr Rev. 2010 May;68(5):280-9. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, OikawaS, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T,Shimada K, Shirato K; Japan EPA lipid intervention study (JELIS) Investigators.Effects of eicosapentaenoic acid on major coronary events inhypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpointanalysis. Lancet. 2007 Mar 31;369(9567):1090-8.

©iStockphoto.com/joannawnuk

Nigella Sativa

A Panacea for Human Disease By Philip Rouchotas MSc, ND, and Heidi Fritz MA, ND Philip Rouchotas MSc, ND Integrated Healthcare Practitioners Editor-in-Chief philip@ihpmagazine.com Bolton Naturopathic Clinic 64 King St W, Bolton, Ontario, L7E1C7 Heidi Fritz, MA, ND Research Fellow, Canadian College of Naturopathic Medicine hfritz@ccnm.edu Bolton Naturopathic Clinic 64 King St W, Bolton, Ontario, L7E1C7

Abstract Nigella sativa, also known as black cumin, is a highly-regarded and prominent herb that has been used in traditional Middle Eastern and Indian systems of medicine. The Prophet Muhammad was recorded as stating that the herb can cure any disease, other than death. Many therapeutic activities have been ascribed to Nigella, including astringent, bitter, stimulant, anthelminthic, carminative, anodyne, expectorant and other effects. In modern research, Nigella has been shown to possess potent anti-inflammatory activity, lipid, glucose, and blood pressure lowering effects, anti-allergic effects, as well as neuroprotective, antimicrobial, and smooth muscle relaxing effects. Preclinical research has indicated potentially important anticancer effects, though this has yet to be investigated in human studies. These effects have been attributed in large part to the constituent thymoquinone. This long list of therapeutic effects demonstrated by scientific research reinforces the traditional view of this impressive herb.

Introduction

Nigella sativa, also known as black cumin, is part of the Ranunculaceae family and an herb with a long history of traditional use in southeast Asia, Egypt, Greece, and the Middle East (Khan 2011). Nigella was regarded as a panacea by the ancients, and played a central role in the medical practice of Middle Eastern and South Asian societies for over 2000 years, where it was used for the treatment of a range of conditions including asthma, headache, dysentery, infection, back pain, dermatological and gastrointestinal conditions (Isik 2010). In traditional Indian medicine, Nigella seeds are astringent, bitter, stimulant, diuretic, emmenagogue, anthelmintic, galactogogue, carminative,

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anodyne, sudorific, febrifuge, expectorant, purgative, and abortifacient (Parrakh 2010). The medieval Islamic philosopher Avicenna wrote of Nigella in his Canon of Medicine, that it stimulates the body’s energy and helps recovery from fatigue and dispiritedness (Parrakh 2010). Mohammed is reported to have said that the seed has the power to cure every disease except death (Parrakh 2010). Medicinally, Nigella has been used in the form of crushed seed, oil, and water extract. The activity of Nigella has been attributed in to its thymoquinone content, which is present in both the fixed and essential oils of Nigella; thymoquinone has been extracted and used therapeutically in isolation (Akhondian 2011, Paarakh 2010).

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The Journal of IHP Nigella oil also contains plant sterols, as well as 25% oleic acid/ 55% linoleic acid, nigellone, and volatile oils including thymol, limonene, and carvacrol (Isik 2010, Paarakh 2010). It is also possible that fibre content may mediate part of the metabolic effects of Nigella.

Mechanism of Action: Preclinical Evidence

There is a wealth of information on Nigella and thymoquinione derived from preclinical research. Thymoquinone appears to be capable of protecting tissues and organs from various types of damage due to antiinflammatory and antioxidant activity, and has also been investigated for its anticancer effects (Woo 2012). In animal models of diabetes, thymoquinone was shown to inhibit cellular expression of the COX-2 enzyme and increased levels of the antioxidant enzyme superoxide dismutase (Al Wafai 2013). In models of hyperlipidemia, Nigella sativa volatile oil and methanol extract have both been shown to reduce triglyceride and increase HDL, as well as decrease hepatic HMG-CoA reductase activity (Ahmad 2013). In smooth muscle tissue, including intestinal and bronchial tissue, thymoquinone has been shown to inhibit spontaneous contraction via inhibition of voltage-gated calcium channels (Ghayur 2012). Thymoquinone has also been shown to inhibit liver fibrosis (Bai 2013); attenuate lung injury and fibrosis (El-Khouly 2012); attenuate diabetic nephropathy (Sayed 2012); prevent E. coli induced tissue damage in bacterial prostatitis (Inci 2013); and prevent dextran sulfate sodium-induced colitis (Lei 2012). In an animal model of epilepsy, thymoquinone was shown to have antioxidant effects in attenuating malondialdehyde (a marker of lipid peroxidation), reduced neurodegenerative changes and neuron loss, and decreased the number of reactive astrocytes (astrogliosis) (Dariani 2013). Thymoquinone has also been shown to have protective effects against amyloid β-induced neurotoxicity, leading to the suggestion that Nigella may have therapeutic potential in Alzheimer’s disease (Alhebshi 2013). Nigella and its constituent thymoquinone have also been extensively studied in lab models for its anticancer effects. Thymoquinone has been shown to have pro-apoptotic effects in breast cancer, including synergistically with tamoxifen (Rajput 2013); and has been

shown to inhibit cancer cell growth and invasiveness in lung, liver, colon, melanoma, and breast cancer cells (Attoub 2012). This is an area where further research is needed to investigate these promising activities.

Clinical Trials

There is a well-developed body of evidence investigating Nigella in humans. Nigella has been shown to have anti-diabetic, blood pressure and cholesterol lowering effects. It also has activity against specific types of infection, possesses anti-allergic effects, and improves rheumatoid arthritis as well as pediatric seizures. Table 1 summarizes all available evidence from human intervention trials concerning the herb as identified through Pubmed and Google Scholar. In metabolic syndrome, Nigella seed has been shown to significantly decrease total cholesterol, LDL, and triglyceride (Dehkordi 2008, Sabzghabaee 2012), improve fasting and post-prandial glucose and HbA1C (Bamosa 2010), decrease systolic blood pressure (Datau 2010, Dehkordi 2008) by almost 10 points in one study (Datau 2010), as well as promote reduction of body weight and waist circumference (Datau 2010). In the area of allergy and asthma, Nigella oil or extract has been shown to significantly reduce symptoms of allergic rhinitis (Kalus 2003,Nikakhlagh 2011), as well as reduce the severity and frequency of asthma symptoms, improve lung function tests, and reduce the need for asthma medications (Boskabady 2007). Also related to respiratory function are two studies showing that Nigella can act as an antimicrobial agent in acute pharyngitis (Dirjomuljono 2008), and improve lung function, respiratory symptoms, as well as medication requirements in patients who were victims of chemical warfare (Boskabady 2008). One study found that Nigella seed in combination with omeprazole was equal to triple therapy in the eradication of H. pylori (Salem 2010). Finally, one study each showed that Nigella was effective in reducing disease activity of rheumatoid arthritis (Gheita 2012), and reduce the frequency of seizures in patients with refractory epilepsy (Akhondian 2011).

Dosage

The effective dosage forms and quantities of Nigella used include 2g of ground seeds in metabolic syndrome or syndrome components (Sabzghabaee 2012); 1-4g seed oil for inflammatory conditions such as September 2013 l www.ihpmagazine.com 65

The Journal of IHP Table 1. Human clinical trials of Nigella sativa Indication

Design

Dose

Outcome

Ref

Metabolic syndrome Hyperlipidemia

RPCT; N=88 subjects with TC>200 mg/dL

• 2g crushed Nigella seeds or placebo (in 500mg caps) x4wk

• Significant decreases in: • TC by 4.78%; LDL by 7.6%; TG by 16.65%. No change in fasting glucose or HDL.

Sabzghabaee 2012 [Abstr]

Metabolic syndrome

RDBPCT; N=40 obese men with no more than stage I hypertension and normal or impaired glucose

• 1.5g Nigella seed or placebo twice daily x 3mo

• Body weight, waist circumference, and systolic blood pressure decreased in the Nigella group only (p<0.05 for all compared to baseline), while these increased in the placebo group: • body weight 77kg à 72 kg at 3 months; • waist circumference 101 à 99.8cm; and systolic BP 130 à 121.

Datau 2010

Metabolic syndrome components

RDBPCT; N=123 patients

• 2g crushed Nigella seed, or placebo x6wk

• “Favorable impact of powdered N. sativa (Kalonji) seed in capsule was noted on almost all variables [body-mass index, waist-hip ratio, blood pressure, fasting blood sugar, lipids, ALT, and creatinine], but results were not statistically significant because of small sample size.”

Qidwai 2009

Hypertension

RDBPCT; N=119 patients with hypertension below 160/100

• 100 or 200mg Nigella boiled seed extract twice daily x8wk, or placebo

• There was a reduction in systolic and diastolic blood pressure in both Nigella groups, in a dose-dependent manner, that was significant compared to placebo (p<0.05 for all). In addition, there was a significant reduction in TC and LDL compared to baseline in the Nigella group (p<0.05 for all).

Dehkordi 2008

Allergic rhinitis

DBPCT; N=66 patients

• Nigella oil 0.5mL x 30d, or placebo

• N. sativa reduced the presence of the nasal mucosal congestion, nasal itching, runny nose, sneezing attacks, turbinate hypertrophy, and mucosal pallor within the first 2 weeks of treatment.

Nikakhlagh 2011 [Abstr]

Asthma

RPCT; N= 29 asthma patients

• 15 mL/kg of 0.1 g% boiled aqueous seed extract daily x 3mo, or placebo solution

• In the Nigella group the following symptoms improved significantly 3 months compared with baseline and with placebo: asthma symptoms, frequency of asthma symptoms per week, chest wheezing, and pulmonary function tests. • Requirements for medications decreased in the Nigella but not in the placebo group.

Boskabady 2007 [Abstr]

Allergy

Report of 4 trials; N= 152 patients with allergic diseases (allergic rhinitis, bronchial asthma, atopic eczema

• Nigella seed oil: 1.5-4.0g per day in 500mg caps

• Subjective report of symptoms severity improved with Nigella treatment.

Kalus 2003

RCT; N=88 patients with non-ulcer dyspepsia and positive H. pylori breath test

• 4 groups: • i) triple therapy OR • ii) 1, 2, or 3g Nigella in addition to omeprazole x4wk; • Nigella as ground seed.

• H. pylori eradication was 82.6, 47.6, 66.7 and 47.8% with triple therapy, and 1g, 2g, and 3g Nigella, respectively. Eradication rates (based on H pylori antibody presence in the stool) with 2g Nigella + omeprazole and triple therapy were not statistically different. • Dyspepsia symptoms improved in all groups to a similar extent.

Salem 2010

Allergy

Infection H. pylori & dyspepsia

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The Journal of IHP Acute tonsillopharyngitis

RDBPCT; N=200 patients with acute tonsillopharyngitis

• Combination of Nigella sativa 360mg and Phyllanthus niruri 50mg extract 3x/d x7d, or placebo

• The Nigella extract led to relief of the pain and difficulty of swallowing within a few hours after the first dose. After 7 days, a significantly greater proportion of patients in the Nigella group had their sore throat completely relieved.

Dirjomuljono 2008 [Abstr]

Rheumatoid arthritis

PCT, x-over; N=40 female RA patients; all were on combined drug therapy.

• 1g Nigella seed oil or placebo (in 500mg caps) x 1mo

• Disease activity improved in 42.5% and 30% of the patients respectively after Nigella. • The number of swollen joints and the duration of morning stiffness also improved.

Gheita 2012

Pediatric seizure

DBPCT x-over; N=22 children with refractory epilepsy

• 1mg/kg thymoquinone from Nigella seed or placebo x 4wk

• Thymoquinone treatment resulted in a significant reduction in seizure frequency compared to placebo (P=0.04).

Akhondian 2011 [Abstr]

Pulmonary function

RDBPCT; N=40 chemical war victims with respiratory symptoms

• 0.375 mL/kg of 50g% boiled aqueous Nigella seed extract daily x 2mo, or placebo

• At study end,pulmonary function tests and respiratory symptoms were significantly improved in the Nigella group compared to the control group (p < 0.01 to p < 0.001). Requirements for medication were decreased in the Nigella but not the placebo group.

Boskabady 2008 [Abstr]

Miscellaneous

allergy and arthritis (Gheita 2012, Kalus 2003); 1mg/kg thymoquinone in pediatric seizure (Akhondian 2011); and varying doses of a boiled aqueous extract (Boskabady 2007, Boskabady 2008).

Safety

Based on the studies in Table 1 as well as the impressive range of activities demonstrated in preclinical research, Nigella appears to possess powerful disease modifying potential in a range of conditions. The only adverse events reported with any consistency among the trials were mild gastrointestinal upset (Akhondion 2011, Bamosa 2010, Salem 2010). Overall, Nigella and/ or thymoquinone appears to have a good safety profile (Al-Ali 2008). In animals, toxicity was demonstrated only at dosages of 250 mg/kg thymoquinone by oral route (maximum tolerated dose) (Abukhader 2012). When given by intraperitoneal injection, toxicity occurred at a dose of between 15-20mg/kg thymoquinone, more than 10-fold the dose used in human trials (Abukhader 2012). Signs of toxicity were acute pancreatitis and peritonitis (Abukhader 2012). In another study, the LD50 of thymoquinone by oral administration was 870.9 mg/kg, more than 100 to 150-fold higher than the therapeutic dose (Al-Ali 2008).

Conclusion

Nigella sativa is a highly regarded herb with a long tradition of use for infection, conditions of inflammation, respiratory and gastrointestinal conditions, and more. Human trials have demonstrated benefits from Nigella seed in metabolic conditions such as dyslipidemia, type 2 diabetes, and hypertension; and Nigella oil or extract in allergy and asthma, inflammatory conditions, infections

including pharyngitis and H. pylori, as well as refractory epilepsy. Further research is needed to elucidate the potential anticancer effects of Nigella suggested by preclinical findings. ■ References

Abukhader MM. The effect of route of administration in thymoquinone toxicity in male and female rats. Indian J Pharm Sci. 2012 May;74(3):195-200. Ahmad S, Beg ZH. Elucidation of mechanisms of actions of thymoquinone-enriched methanolic and volatile oil extracts from Nigella sativa against cardiovascular risk parameters in experimental hyperlipidemia. Lipids Health Dis. 2013 Jun 13;12(1):86. [Epub ahead of print] Akhondian J, Kianifar H, Raoofziaee M, Moayedpour A, Toosi MB, Khajedaluee M. The effect of thymoquinone on intractable pediatric seizures (pilot study). Epilepsy Res. 2011 Jan;93(1):39-43. Al-Ali A, Alkhawajah AA, Randhawa MA, Shaikh NA. Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats. J Ayub Med Coll Abbottabad. 2008 Apr-Jun;20(2):25-7. Alhebshi AH, Gotoh M, Suzuki I. Thymoquinone protects cultured rat primary neurons against amyloid β-induced neurotoxicity. Biochem Biophys Res Commun. 2013 Apr 19;433(4):362-7. Al Wafai RJ. Nigella sativa and thymoquinone suppress cyclooxygenase-2 and oxidative stress in pancreatic tissue of streptozotocin-induced diabetic rats. Pancreas. 2013 Jul;42(5):841-9. September 2013 l www.ihpmagazine.com 67

Attoub S, Sperandio O, Raza H, Arafat K, Al-Salam S, Al Sultan MA, Al Safi M, Takahashi T, Adem A. Thymoquinone as an anticancer agent: evidence from inhibition of cancer cells viability and invasion in vitro and tumor growth in vivo. Fundam Clin Pharmacol. 2012 Jun 11. Bai T, Lian LH, Wu YL, Wan Y, Nan JX. Thymoquinone attenuates liver fibrosis via PI3K and TLR4 signaling pathways in activated hepatic stellate cells. Int Immunopharmacol. 2013 Feb;15(2):275-81. Bamosa AO, Kaatabi H, Lebdaa FM, Elq AM, Al-Sultanb A. Effect of Nigella sativa seeds on the glycemic control of patients with type 2 diabetes mellitus. Indian J Physiol Pharmacol. 2010 Oct-Dec;54(4):344-54. Boskabady MH, Farhadi J. The possible prophylactic effect of Nigella sativa seed aqueous extract on respiratory symptoms and pulmonary function tests on chemical war victims: a randomized, double-blind, placebo-controlled trial. J Altern Complement Med. 2008 Nov;14(9):1137-44. Boskabady MH, Javan H, Sajady M, Rakhshandeh H. The possible prophylactic effect of Nigella sativa seed extract in asthmatic patients. Fundam ClinP harmacol. 2007 Oct;21(5):559-66. Erratum in: Fundam Clin Pharmacol. 2008 Feb;22(1):105. Dariani S, Baluchnejadmojarad T, Roghani M. Thymoquinone Attenuates Astrogliosis, Neurodegeneration, Mossy Fiber Sprouting, and Oxidative Stress in a Model of Temporal Lobe Epilepsy. J Mol Neurosci. 2013 Jun 23. [Epub ahead of print] Datau EA, Wardhana, Surachmanto EE, Pandelaki K, Langi JA, Fias. Efficacy of Nigella sativa on serum free testosterone and metabolic disturbances in central obese male. Acta Med Indones. 2010 Jul;42(3):130-4. Dehkordi FR, Kamkhah AF. Antihypertensive effect of Nigella sativa seed extract in patients with mild hypertension. Fundam Clin Pharmacol. 2008 Aug;22(4):447-52. Dirjomuljono M, Kristyono I, Tjandrawinata RR, Nofiarny D. Symptomatic treatment of acute tonsillopharyngitis patients with a combination of Nigella sativa and Phyllanthus niruri extract. Int J Clin Pharmacol Ther. 2008 Jun;46(6):295-306. El-Khouly D, El-Bakly WM, Awad AS, El-Mesallamy HO, El-Demerdash E. Thymoquinone blocks lung injury and fibrosis by attenuating bleomycin-induced oxidative stress and activation of nuclear factor Kappa-B in rats. Toxicology. 2012 Dec 16;302(2-3):106-13. Ghayur MN, Gilani AH, Janssen LJ. Intestinal, airway, and cardiovascular relaxant activities of thymoquinone. Evid Based Complement Alternat Med. 2012;2012:305319. Gheita TA, Kenawy SA. Effectiveness of Nigella sativa oil in the management of rheumatoid arthritis patients: a placebo controlled study. Phytother Res. 2012 Aug;26(8):1246-8.

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Inci M, Davarci M, Inci M, Motor S, Yalcinkaya FR, Nacar E, Aydin M, Sefil NK, Zararsiz I. Anti-inflammatory and antioxidant activity of thymoquinone in a rat model of acute bacterial prostatitis. Hum Exp Toxicol. 2013 Apr;32(4):354-61. Işik H, Cevikbaş A, Gürer US, Kiran B, Uresin Y, Rayaman P, Rayaman E, Gürbüz B, Büyüköztürk S. Potential adjuvant effects of Nigella sativa seeds to improve specific immunotherapy in allergic rhinitis patients. Med Princ Pract. 2010;19(3):206-11. Kalus U, Pruss A, Bystron J, Jurecka M, Smekalova A, Lichius JJ, Kiesewetter H. Effect of Nigella sativa (black seed) on subjective feeling in patients with allergic diseases. Phytother Res. 2003 Dec;17(10):1209-14. Khan MA, Chen HC, Tania M, Zhang DZ. Anticancer activities of Nigella sativa (black cumin). Afr J Tradit Complement Altern Med. 2011;8(5 Suppl):226-32. Lei X, Liu M, Yang Z, Ji M, Guo X, Dong W. Thymoquinone prevents and ameliorates dextran sulfate sodium-induced colitis in mice. Dig Dis Sci. 2012 Sep;57(9):2296-303. Nikakhlagh S, Rahim F, Aryani FH, Syahpoush A, Brougerdnya MG, Saki N. Herbal treatment of allergic rhinitis: the use of Nigella sativa. Am J Otolaryngol. 2011 Sep-Oct;32(5):402-7. Paarakh PM. Nigella sativa Linn. – a comprehensive review. Indian Journal of Natural Products and Resources. 2010 Dec;1(4):409-29. Qidwai W, Hamza HB, Qureshi R, Gilani A. Effectiveness, safety, and tolerability of powdered Nigella sativa (kalonji) seed in capsules on serum lipid levels, blood sugar, blood pressure, and body weight in adults: results of a randomized, doubleblind controlled trial. J Altern Complement Med. 2009 Jun;15(6):639-44. Rajput S, Kumar BN, Sarkar S, Das S, Azab B, Santhekadur PK, Das SK, Emdad L, Sarkar D, Fisher PB, Mandal M. Targeted apoptotic effects of thymoquinone and tamoxifen on XIAP mediated Akt regulation in breast cancer. PLoS One. 2013 Apr 17;8(4):e61342. Sabzghabaee AM, Dianatkhah M, Sarrafzadegan N, Asgary S, Ghannadi A. Clinical evaluation of Nigella sativa seeds for the treatment of hyperlipidemia: a randomized, placebo controlled clinical trial. Med Arh. 2012;66(3):198-200. Salem EM, Yar T, Bamosa AO, Al-Quorain A, Yasawy MI, Alsulaiman RM, Randhawa MA. Comparative study of Nigella Sativa and triple therapy in eradication of Helicobacter Pylori in patients with non-ulcer dyspepsia. Saudi J Gastroenterol. 2010 Jul-Sep;16(3):207-14. Sayed AA. Thymoquinone and proanthocyanidin attenuation of diabetic nephropathy in rats. Eur Rev Med Pharmacol Sci. 2012 Jun;16(6):808-15. Woo CC, Kumar AP, Sethi G, Tan KH. Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol. 2012 Feb 15;83(4):443-51.

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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 andplacebo Endolimax After 6inweeks of timeshartmanni, increased in the group,nana. but decreased the ch-OSA Biology there wasfrequently completeexists resolution of parasitic 8 cases, while Blastocystis hominis decreased in three treatment, suggesting decreased skin elasticityscores in the placebo group The element silicon as a compound withinfection ingroup and increased skin elasticity in the ch-OSA group. Finally, visual oxygen, silicon dioxide or silica (Si2O); in solution, silica more cases; gastrointestinal symptoms improved in 7exists of the 11 subjects who had presented with Blastocystis hominis analog scale scores for nail and hair brittleness were significantly as a hydrated form called orthosilicic acid (OSA) (Jurkic 2013). infection. (Force 2000) lower in the ch-OSA group compared to baseline scores. Choline-stabilized orthosilicic acid (ch-OSA) is, as the name suggests, a uniquely effective and stable complex of choline Animal and In vitro studies and OSA in water solution. ch-OSA has been shown to promote dose: Carvacrol in immunocompromised rats was Recommended found to be as adult effective as treatment with Nystatin, reducing formationfor of oral type candidiasis I collagen, a component of bone and connecDrops: Mix 5 drops in a glass of juice twice a day (morning and thetive number of colony forming unitsis(CFU’s) and completely tissue (Spector 2008), and silicon present at 1-10 ppm in clearing hyphae from oral surfaces when given for 8 days evening) and drink immediately or as directed by a health care (Chami 2004).2007). In vitro, carvacrol was determined to exert an inhibitory effect against 6 different strains of Candida species hair (Wickett practitioner.

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Non-medicinal ingredients: scores below -1.5 received either1000 mg calcium and 800 IU Choline chloride, glycerol, purified water. vitamin D3, along with one of three different ch-OSA doses (3, 6 and 12 mg Si) or placebo. In the 136 women who completed the study, there was a trend for ch-OSA to confer additional benefit to References Barel A, Calomme M, Timchenko A, De Paepe K, Demeester N, calcium plus vitamin D3 treatment, especially for markers of bone Rogiers V, Clarys P, Vanden Berghe D. Effect of oral intake of formation, which included: osteocalcin, bone specific alkaline choline-stabilized orthosilicic acid on skin, nails and hair in phosphatase, procollagen type I N-terminal propeptide (P1NP). women with photodamaged skin. Arch Dermatol Res. 2005 The addition of ch-OSA showed significant benefit on formation Oct;297(4):147-53. of type I collagen formation after 12 months of treatment for the 6 and 12 mg Si doses, compared to placebo. There was no Calomme M, Geusens P, Demeester N, Behets GJ, D’Haese P, significant change in lumbar spine bone mineral density (BMD). Sindambiwe JB, Van Hoof V, Vanden Berghe D. Partial prevenFigure 1: Structure of Carvacrol (left) and Thymol (right) However, subgroup analysis showed a significant improvement tion of long-term femoral bone loss in aged ovariectomized rats in BMD at the femoral neck for women who had baseline T-score supplemented choline-stabilized orthosilicic acid. Calcif aureus and epidermis, and attenuates biofilm formation in vitro (Nostra 2004;with 2007). <-1 at baseline. There were no ch-OSA related adverse events Tissue Int. 2006 Apr;78(4):227-32. Toxicology observed and biochemical safety Essential oil extracts categorically doses,LM, and are therefore given in dropand doses; Cepanec I, Pavelićtypically SK, Pavelić K. Biological parameters remainedare within the normalknown range. to be toxic in high Jurkić essential oils should not be used internally by pregnant or breastfeeding women. Animal studies toand date, however, indicate therapeutic effects of ortho-silicic acid some ortho-silicic A study in the standard animal model for post-menopausal bone acid-releasing compounds: New perspectives for therapy. Nutr relative safety of Oregano oil. loss showed similar results, with ch-OSA resulting in increased Metab (Lond). 2013 Jan 8;10(1):2. Carvacrol was content shown to be hepatoprotective againstasischemia bone mineral in femoral and lumbar locations, well as and reperfusion injury in rats; both carvacrol and silymarin had similar beneficial effects on AST and ALT levels (Canbek 2007). increased liver rate of in rats LassusCarvacrol A. Colloidalalso silicic acid for oral andregeneration topical treatment decreased bone resorption (Calomme 2006). aged skin, fragile hair and brittle nails in females. J Int Med Res. after partial hepatectomy (Uyanoglu 2008). 1993 is Jul-Aug;21(4):209-15. Hair, Skin and Nails of carvacrol show only weak activity; carvacrol Mutagenicity studies excreted in urine after 24 hours in large quantities, In a randomized, double blind,and placebo controlled trial, (De Vincenzi 2004). unchanged or as glucoronide sulphate conjugates Spector TD, Calomme MR, Anderson SH, Clement G, Bevan L, supplementation with ch-OSA was shown to improve hair tensile Demeester N, Swaminathan R, Jugdaohsingh R, Berghe DA, strength, elasticity, and thickness (Wickett 2007). A total of 48 Powell JJ. Choline-stabilized orthosilicic acid supplementation References women with fine hair were given 10mg silicon as ch-OSA daily, as an adjunct to calcium/vitamin D3 stimulates markers of bone Canbek M, Uyanoglu M, Bayramoglu G,found Senturk or a placebo for nine months. Researchers thatH, theErkasap elastic N, Koken T, Uslu S, Demirustu C, Aral E, Husnu Can Baser K. in osteopenic females: a randomized, placeboEffects of carvacrol defects of ischemia-reperfusion in the ratformation liver. Phytomedicine. 2008 Jan. gradient decreased on in both groups, but the change was significontrolled trial. BMC Musculoskelet Disord. 2008 Jun 11;9:85. smallerM inet theal.ch-OSA group (-4.52%) compared to placebo Decantly Vincenzia Constituents of aromatic plants: carvacrol. Fitoterapia 2004; 75(7-8): 801-804. E, Barel A, Demeester N, Clarys P, Vanden group Similarly, break load changed in theoil of Wickett Force M(-11.9%). et al. Inhibition of enteric parasitessignificantly by emulsified oreganoRR,inKossmann vivo. Phytother Res. 2000 May;14(3):213-4. D, Calomme M. Effect of oral intake of choline-stabilized placeboRJ, group (-10.8%) but in thePJ, ch-OSA supplemented Lambert Skandamis PN,not Coote Nychas GJ. A study of theBerghe minimum inhibitory concentration and mode of action of orthosilicic acid on hair tensile strength and morphology in womgroup (-2.20%). Notably, the cross sectional area or “thickness” of oregano essential oil, thymol and carvacrol. J Appl Microbiol. 2001 Sep;91(3):453-62. en with fine hair. Arch Dermatol Res. 2007 Dec;299(10):499-505. the hair shaft increased significantly after 9 months in the ch-OSA Nostro A, Roccaro AS, Bisignano G, Marino A, Cannatelli MA, Pizzimenti FC, Cioni PL, Procopio F, Blanco AR. Effects of supplemented subjects only.

oregano, carvacrol and thymol on Staphylococcus aureus and Staphylococcus epidermidis biofilms. J Med Microbiol. In a second RCT, 50 women with photodamaged facial skin were 2007;56(Pt 4):519-23. randomized to receive either 10mg silicon as ch-OSA or placebo Nostro A et Susceptibility of methicillin-resistant to oregano essential oil, carvacrol and thymol. FEMS daily for 20 al. weeks (Barel 2005). Skin roughness (microrelief)staphylococci paramMicrobiol Lett. 2004;230(2):191-5. eters increased in the placebo group but decreased in the ch-OSA Salgueiro LRthis et al. Chemical composition and group, and change was significant between theantifungal two groups.activity of the essential oil of Origanum virens on Candida species. The difference between longitudinal and lateral shear propagation 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

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Vitamin E

Obstacles and opportunities in cancer prevention and treatmentâ&#x20AC;&#x201A; By Elizabeth Stavros ND, Amy Kroeker ND, and Akbar Khan MD Akbar Khan, MD Medicor Cancer Centres 4576 Yonge St, Suite 301 Toronto, ON M2N 6N4 akhan@medicorcancer.com Elizabeth Stavros, ND Rethink Health Toronto, ON Elizabeth@DoctorStavros.com Amy Kroeker, ND www.AmyKroekerND.com

Abstract Vitamin E is one of the most researched compounds in the medical community because of what is believed to be its reduced risk association with a multitude of diseases, including cancer. There are eight forms of vitamin E, four tocopherols and four tocotrienols. Alpha tocopherol is by far the most studied form because it is the most biologically active (Aggarwal 2010). Gamma tocopherol and tocotrienols have shown the greatest promise with respect to recent cancer research. Gamma tocopherol has been found to prevent cancer cell growth both in vitro and in animal models by decreasing the formation of mutagens (Stone 2004). Cell-based studies have shown that tocotrienols exhibit even stronger anticancer activities than other forms of vitamin E, including gammatocopherol (Jiang 2000). For all forms of vitamin E, additional research is needed that involves human trials to understand the relationship between dietary supplementation, required dosages, and the long-term risks and benefits.

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Introduction

Since Herbert M. Evans discovered vitamin E in his laboratory at the University of California, Berkley in 1922, vitamin E has become one of the most researched compounds within the medical community (Packer 2001). Gamma tocopherol and tocotrienols are often discussed within the medical literature as providing the greatest opportunities for disease prevention and treatment. The results of several studies have indicated that the tocotrienols may have stronger bioactivity than the tocopherols. Both types have shown anti-proliferative, pro-apoptotic and

Well-designed human intervention trials with gamma tocopherol are needed to yield more definitive information on its cancer-preventive activities, and the most effective route of administration (ie. oral vs. injectable). cyclooxygenase-2-inhibiting effects in in vitro studies (Wada 2012). These types of vitamin E have shown promise in treatment of a variety of cancers, including prostate cancer in men and breast cancer in women (Nesaretnam 2010, Sylvester 2005). The purpose of this paper is to examine some of the existing research regarding the potential benefits of gamma tocopherol and tocotrienols in relation to cancer prevention and treatment.

Vitamin E and Cancer

Before discussing the research that has shown the benefits of gamma tocopherol and tocotrienols with respect to cancer, it is important to briefly note the somewhat negative findings associated with supplemental alpha tocopherol intake and cancer. Alpha tocopherol is the most biologically active form of vitamin E in the human body and all other forms of vitamin E are measured

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in alpha tocopherol equivalents (National Academies Press 2000). A large randomized clinical trial, the SELECT trial, began in 2001 to determine whether daily supplementation with vitamin E (400 IU, as alpha tocopherol), with or without selenium (200 mcg), reduced the number of new prostate cancers in 35,533 healthy men over 50 years old. The trial was discontinued in 2008 when an analysis found that the supplements, taken alone or together for about five years, did not prevent prostate cancer. Results from an additional 1.5 years of follow-up from this trial showed that the men who had taken the alpha tocopherol had a 17 percent increased risk of prostate cancer compared placebo (Klein 2011). Other research has suggested that taking too much vitamin E can have pro-oxidant instead of anti-oxidant effects on cells (Brown 1997). Due to this effect, alpha tocopherol taken in high dosages may create a set of conditions in the body resulting in cancer cell formation that would not have otherwise occured. The warning that seems appropriate is that supplemental alpha tocopherol should not be viewed as a way of reducing cancer risk or cancer cell growth.

Gamma Tocopherol in Cancer Treatment

Research on human epithelial cells has indicated that gamma tocopherol, one of the forms of vitamin E and the most prevalent in the North American diet, has antiinflammatory properties as a COX-2 inhibitor that may be important in preventing a variety of diseases including cancer and cardiovascular disease (Jiang 2000). Research has shown that increased intake of gamma tocopherol was associated with a reduced risk of prostate cancer (Moyad 1999). Gamma tocopherol is superior to alpha tocopherol in the trapping of reactive nitrogen species, inhibition of COX-2 activity, activation of PPAR-Îł and suppression of inflammation. Jihyeung et al. (2010) propose that a mixture of tocopherols, at ratios similar to those in our diet, could be a

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better cancer chemopreventive agent, based on their lab results demonstrating that gamma tocopherol inhibited colon, mammary, prostate and lung carcinogenesis in animal models. Human cell line study findings indicate that gamma tocopherol has potent anti-inflammatory activity and that at physiological concentrations, it may play an important role in human disease prevention (Jiang 2000). Well-designed human intervention trials with gamma tocopherol are needed to yield more definitive information on its cancer-preventive activities, and the most effective route of administration (ie. oral vs. injectable).

Tocotrienols in Cancer Treatment

As compared to tocopherols, tocotrienols have been found to be much more effective in prevention and inhibition of cancer cell growth in the body (Sylvester 2005). Part of the reason for this is that tocotrienols are more likely than tocopherols to achieve high cellular concentrations. The potential for higher cellular concentration of tocotrienols results in mitochondrial toxicity and apoptosis, a reduction of cancer cell reproduction, and the prevention of new cancer cell formation (Viola 2012). It has been noted that tocotrienols target different molecular structures than tocopherols. Specifically, the anti-inflammatory properties of tocotrienols have been found to suppress the transcription factor NF-kB, which has been linked to tumorigenesis and inhibition of HMG-CoA reductase, mammalian DNA polymerases, and some protein tyrosine kinases (Aggarwal 2010). Because of the unique anti-inflammatory properties and cell line targeting that occurs with tocotrienols, patients suffering from various types of cancers, specifically breast and prostate cancer, may be able to take a lower dosage of tocotrienols as compared to tocopherols, and achieve better results. This is important considering that research has indicated that high levels of vitamin E supplementation, in the form of alpha tocopherol, has been associated with increased levels of hemorrhagic stroke (Schurks 2010). Research suggests that for women, taking tocotrienols as a dietary supplement may reduce the risk of developing breast cancer (Sylvester 2010). Part of the benefit of tocotrienols is indeed related to the lower dosages that are required in order to achieve the anti-inflammatory and anti-cancer properties. Other research has indicated that tocotrienols may increase immune function and response in the body (Nesaretnam 2012). The rationale is that tocotrienols bind to estrogen receptor beta

(ER-beta) leading to alteration of cell morphology and apoptosis of breast cancer cells (Nesaretnam 2012). Tamoxifen is currently one of the standard treatment in patients with estrogen receptor positive tumors. New research indicates that a combination of tamoxifen with tocotrienols may prolong the life of women with breast cancer (Nesaretnam 2012). A common problem with tamoxifen therapy is that patients develop resistance to the drug. Using a combination of tocotrienols and tamoxifen may reduce the problems that occur once patients develop tamoxifen resistance while also acting synergistically to extend breast cancer-specific survival (Nesaretnam 2012).

Therapeutic Dosing

The eight forms of vitamin E are not interconvertible within the human body. Instead, serum and intracellular concentrations of tocopherols and tocotrienols each rely upon the affinity of the hepatic alpha-tocopherol transfer protein (alpha-TTP) for their selective retention in plasma (National Academies Press 2000). As well, in vivo concentrations of vitamin E rely on the bodyâ&#x20AC;&#x2122;s ability to absorb each form. Typically, this absorption is below 80% and for some forms of vitamin E can be as low as 10% absorption from the gastrointestinal tract. Although it is common for supplemental vitamin E products to measure doses in International Units (IU), this format is outdated. Most commonly, milligrams of alpha-tocopherol equivalents (alpha-TE) are used to show dosage and this more clearly represents the ability of the body to absorb and utilize different forms of vitamin E (National Academies Press 2000). The conversion factor is based on 0.67mg (alpha-TE)/IU. 1000mg/day (1500IU) is considered the Upper Limit (UL) for vitamin E supplementation based on statistical analysis of adverse effects in high dose studies as well as other factors (National Academies Press 2000). However, research by Johns Hopkins University showed that vitamin E supplementationin excess of 400IU daily for one year in the alpha tocopherol form resulted in increased all-cause mortality and should be avoided (Miller 2005). In terms of therapeutic dosing for maximal cancer prevention and apoptotic potential, there are no standardized protocols. Since many of the studies showing benefit for cancer treatment have been in vitro or in animal models, adult human dosing is difficult to determine. Nesaretnam et al. (2010) found

September 2013 l www.ihpmagazine.com 73

that during a five year randomized controlled trial on women undergoing tamoxifen therapy, risk of mortality due to breast cancer was 60% lower in the intervention group supplemented with 400mg tocotrienols in the form of a tocotrienol rich fraction (TRF) daily versus the controls. This dosing provides a guideline for further investigation. Generally, dietary sources are considered safe due to the bodies inefficient absorption mechanisms for all forms of vitamin E. At higher levels, vitamin E may inhibit absorption of other fat soluble vitamins (A, D, and K). In particular, vitamin K may be decreased in some individuals supplementing with vitamin E and so caution should be taken at higher doses to monitor blood coagulation.

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During cancer chemotherapy and radiotherapy, a research review (Lawenda 2008) suggests that supplementing any antioxidant (including vitamin E) should be avoided due to the potential for anti-oxidants to protect any cell regardless of whether it is a cancer cell or not. Most definitely, dosing protocols specific to cancer treatment should be researched further once clinical trials elucidating effectiveness have been undertaken. Common dosages on supplements range from a daily dose of 60mg mixed tocopherols in professional brand multivitamins to 200-400mg daily of tocotrienols in the form of a tocotrienol rich fraction (TRF) from palm oil.

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The research that has been reviewed suggests that both gamma tocopherol and tocotrienols have anti-inflammatory properties that can reduce cancer cell growth in the body. Tocotrienols may have a greater ability to reduce the risk of cancer development and spread, especially with estrogen receptor positive breast cancer in women.

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Conclusion

The research that has been reviewed suggests that both gamma tocopherol and tocotrienols have antiinflammatory properties that can reduce cancer cell growth in the body. Tocotrienols may have a greater ability to reduce the risk of cancer development and spread, especially with estrogen receptor positive breast cancer in women. Much more research regarding the specific supplemental dosages of the sup-types of vitamin E is required. Clinical trials are necessary to establish safe and effective dosing protocols. What does seem clear is that gamma tocopherol, tocotrienols, and mixed tocopherols are safer forms of supplementation and provide a higher level of benefit than alpha tocopherol. ■

References:

Aggarwal, B. B., Sundaram, C., Prasad, S. & Kannappan, R. Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases. Biochemical Pharmacology. 2010. 80(11), 1613-1631. Dietrich, M., Traber, M. G., Jacques, P. F., Cross, C. E., Hu, Y. & Block, G.Does γ-Tocopherol play a role in the primary prevention of heart disease and cancer? A review. Journal of the American College of Nutrition. 2006. 25(4), 292-299. Jiang, Q., Elson-Schwab, I., Courtemanche, C. & Ames, B. N. Gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. Proceedings of the National Academy of Sciences. 2000. 97(21), 11494-11499. Jihyeung, Ju, Picinich S, Yang Z, et al. Cancer-preventive activities of tocopherols and tocotrienols. J Carcinogenesis. 2010 April; 31(4): 533–542. Klein EA, Thompson Jr. IM, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011;306:1549-1556. Lawenda, B.D., Kelly, K.M., Ladas, E.J., Sagar, S.M., Vickers, A., Blumberg, J.B. Should Supplemental Antioxidant Administration Be Avoided During Chemotherapy and Radiation Therapy? J Natl Cancer Inst. 2008. 100(11), 773-83.

Moyad, M. A., Brumfield, S. K. & Pienta, K. J. Vitamin E, alpha- and gamma-tocopherol, and prostate cancer. Seminars in Urologic Oncology. 1999. 17(2), 85-90. National Institutes of Health. Dietary Supplement Fact Sheet: Vitamin E. 2011. Retrievedfrom: http://ods.od.nih.gov/ factsheets/vitamine/. National Academies Press. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC, 2000. Nesaretnam, K., Meganthan, P., Veerasenan, S. D. & Selvadurary, K. R. Tocotrienols and breast cancer: the evidence to date. Genes Nutr. 2012. 7, 3-9. Nesaretnam, K., Selvaduray, K.R., Razak, G.A., Veerasenan, S.D., Gomez, P.A. Effectiveness of Tocotrienol Rich Fraction Combined with Tamoxifen in the Management of Women with Early Breast Cancer: A Pilot Clinical Trial. Breast Cancer Research. 2010. 12; R81. Packer, L. Weber, S. U. & Rimbach, G. Molecular aspects of alpha-tocotrienol antioxidant action and cell signaling. Journal of Nutrition.2001. 131(2), 369S-373S. Schurks, M., Glynn, R.J., Rist, P.M., Tzourio, C., Kurth, T. Effects of Vitamin E on Stroke Subtypes: Meta-analysis of Randomized Controlled Trials. BMJ. 2010. 341. Stone W, Krishnan K, Campbell S, Qui M, Whaley S, Yang H. Tocopherols and the Treatment of Colon Cancer. Annals of the New York Academy of Sciences Volume 1031, Vitamin E and Health pages 223–233, December 2004 Sylvester, P. W. & Shah, S. J. Mechanisms mediating the antiproliferative and apoptotic effects of vitamin E in mammary cancer cells. Frontiers in Bioscience.2005. 10, 699-709. Sylvester, P. W., Kaddoumi, A., Nazzal, S. & El Sayed, K. A. The value of tocotrienols in the prevention and treatment of cancer. Journal of the American College of Nutrition. 2010. 29(3), 3245-3335. Viola, V., Pilolli, F., Piroddi, M., Pierpaoli, E., Orlando, F., Provinciali, M., Betti, M., Mazzini, F. &Galli, F. Why tocotrienols work better: insights into the in vitro anti-cancer mechanism of vitamin E. Genes Nutr. 2012. 7, 29-41. Wada, S. Cancer preventive effects of vitamin E. Curr Pharm Biotechnol. 2012 Jan;13(1):156-64.

Miller, E.R.3rd, Pastor-Barriuso, R., Dalal, D., Riemersma, R.A., Appel, L.J., Guallar, E. Meta-analysis: High Dosage Vitamin E Supplementation May Increase All-cause Mortality. Ann Int Med. 2005. 142:37-46.

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Iron & Diabetes A reviewâ&#x20AC;&#x201A; By William R Ware, PhD

William R. Ware, PhD Emeritus Professor, Faculty of Science University of Western Ontario warewr@rogers.com

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Abstract Both anemia and iron overload are commonly encountered problems in clinical practice. In between is a huge gray area of iron levels, measured by various markers, that fall in the normal reference ranges and are viewed as not a cause for concern. However, to take as an example the risk of acute cardiovascular events in women, the prevalence is very small prior to menopause and then increases to approach the risk level where postmenopausal women have a prevalence similar to adult men. This has been attributed to the very low systemic iron burden in premenopausal women and has encouraged the questioning of the optimum levels in both men and postmenopausal women. This is not a frivolous suggestion since the iron levels, or more properly the iron stores, are easily adjustable by blood donation or phlebotomy and blood iron stores of premenopausal women are easily achieved by adult men, apparently with negligible risk of side effects including anemia. Rather like the argument of those who believe in statins that the lower the LDL the better, a valid concern can be raised as to the appropriate range of iron stores in both adult men and postmenopausal women. Elevated iron stores lead to elevated iron available for redox reactions which act as generators of reactive oxygen species and highly significant inflammation, both of which are associated with a number of chronic diseases having inflammation as a part of their etiology. In this review, the connection between iron overload and diabetes will be discussed.

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Introduction

It is well established that humans need a certain level of iron for health, but higher levels are potentially toxic (Kell 2009). From the point of view of evolution, normal stores of iron during reproductive years provided reserves for hemorrhage or periods of severe dietary restrictions or starvation. However there is no homeostatic mechanism for excreting excess iron to maintain a certain level. Hemochromatosis and thalassaemia involve very high pathological iron levels, but even mildly elevated iron stores over time which are implicated in excessive redox (oxidation-reduction) reactions have been associated with the pathogenesis of cancer, neurodegenerative disorders, atherosclerosis, cardiovascular disease, peripheral artery disease and diabetes (Kell 2009). Iron is mostly sequestered as ferritin, a ubiquitous intracellular protein that both stores iron and releases it in a controlled manner in a safe form. Transferrin also ties up iron but can be saturated. Its function is to transport iron through the blood to the liver, spleen and bone marrow, with the iron in part coming from diet and erythrocyte breakdown. Significant serum levels of non-transferrin bound iron can also be present. It is redox active, and appears to be present even when transferrin saturation is absent (Lee 2006). The blood level of ferritin is the most commonly used marker for the magnitude of iron stores and iron overload. Elevated ferritin levels are not always a true indicator of iron stores since it is an acute phase reactant. In most studies involving diabetes, this does not appear to be an issue. Mean ferritin levels in the US population study NHANES III were for men about 150 ng/mL, for menstruating women ages 17-49, 25-35 ng/mL, and for menopausal women ages 50-59, 60 ng/mL and for ages > 60, about 90-100 ng/mL (Zacharski 2000). Low levels of stored iron in premenopausal women have been frequently evoked as an explanation for the well known low risk of cardiovascular disease. These numbers raise concerns that the normal male level or the level found in older postmenopausal women may be associated with elevated risk of morbidity or mortality.

Toxicity of Iron

The toxicity of iron is related to its role in producing oxidative damage and the ease with which it is reversibly oxidized and reduced. Ferrous iron catalyzes the production of the highly toxic and reactive hydroxyl radical from hydrogen peroxide, whereas superoxide dismutase serves to equilibrate superoxide and peroxide. Oxidized iron regenerates reduced iron by reacting with superoxide with redox cycling. This results in reactive oxygen species (ROS) responsible for

oxidative stress. When these overwhelm the antioxidant capacity, damage occurs which has been related to diseases of aging and inflammation (Brewer 2007). One view is that the dangers of excess iron operate through inadequately liganded (tied up) iron ions. When the ions are tightly liganded they are unreactive but weak ligand formation leaves some reactive free iron. The pathophysiology of iron is thus related to the availability of so-called catalytic iron, or iron that is available to participate in free radical reactions. Due to their weak antioxidant defences the pancreatic Î˛-cells are particularly susceptible to oxidative damage such as can be caused by iron-generated reactive oxygen species (Tiedge 1997). In fact, iron has been used to induce diabetes in animals. Correlations with ferritin levels are an indirect measure of risk from iron-induced oxidative stress, and high ferritin levels correlate with elevated inflammatory cytokine levels (Depalma 2010).

The Association between Iron Levels, Diabetes and the Metabolic Syndrome

The potential role of iron in the pathogenesis of diabetes is suggested by several observations (Rajpathak 2009): (1) Increased incidence of diabetes is seen in patients with diverse causes of iron overload. (2) The reduction in iron load by either chelation or phlebotomy can improve glycemic control or reverse diabetes. (3) Dietary intake of heme iron (e.g. red meat) and concomitant increases in iron stores is associated with the risk of developing diabetes. (4) Insulin sensitivity and insulin secretion are increased by frequent blood donation. The molecular mechanisms are numerous and incompletely understood but include oxidative stress, modulation of adipokines and intracellular singling transduction pathways (Simcox 2013, Swaminathan 2007). It has been argued that the modest elevations of ferritin observed in diabetes may be a consequence of the disorder rather than a causal factor impacting insulin resistance and Î˛-cell function and apoptosis (Jehn 2007). However, evidence suggests otherwise. Excessive amounts of nontransferrin-bound iron, the form most susceptible to redox activity, are found in diabetic patients with a strong gradient for disease severity (Lee 2006). Furthermore, as will be discussed below, phlebotomy in type 2 diabetes results in improvements in glycemic control and insulin sensitivity which also supports the hypothesis that iron plays a pathogenic role. Two recently published systematic reviews plus metaanalyses have examined the association of diabetes incidence with ferritin levels. One study (Zhao 2012) reports a meta-analysis of 12 prospective or crosssectional studies which analyzed ferritin levels and involved 4366 type 2 diabetes patients and over 41,000 September 2013 l www.ihpmagazine.com 77

STUDY

HIGHEST Q (ng/mL)

LOWEST Q (ng/mL)

ODDS RATIO

Jiang

≥107

<21

2.68

Forouhi

≥72

<18

2.55

It would seem that for women in this age group, levels similar to the NHANES average already carry significant risk. A recent review and meta-analysis relates to the above. At issue is the association between red meat intake and risk of developing type 2 diabetes. A 19% increase was found per 100 g/day of red meat and a 51% increase per 50 g/day of processed red meat (Micha 2012).

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The metabolic syndrome (MetS) is recognized as a risk factor for diabetes. Population studies find an association between ferritin levels and the risk of MetS in the US (Jehn 2004), Korea (Lee 2011), and Germany (Wrede 2006). Ferritin levels are associated with the MetS in postmenopausal but not premenopausal Korean women (Cho 2011), High levels of ferritin in a Chilean population correlated not only with a three-fold increase in developing MetS but for high levels of oxidative stress indicated by serum markers, there was a 21 fold increase in the development of this syndrome when the highest vs. the lowest quartiles were compared (Leiva 2013).

Clinical use of Phlebotomy to reduce Body Iron Stores

Both blood donation and phlebotomy can dramatically reduce iron stores (Houschyar 2012, Zacharski 2011). Repeated blood letting very efficiently lowers ferritin levels even if the initial values are very high such as seen in hemochromatosis. Furthermore, no induced anemia has been reported. The following studies are of interest: • In a randomized controlled trial with metabolic syndrome patients, reduction of mean ferritin levels from 183 to 105 ng/mL using phlebotomy resulted in significant reductions in blood glucose, HbA1c, and systolic blood pressure. Changes in blood pressure and the HOMA-IR insulin resistance index correlated with ferritin reduction (Houschyar 2012). • In a study comparing lacto-ovo vegetarians and meat eaters, the former were found to have mean ferritin levels of 35 ng/mL compared to 72 ng/mL for meats eaters and to have higher insulin sensitivity. When body stores of iron were lowered by phlebotomy in the meat eating group there was a 40% increase in insulin mediated glucose disposal (Hua 2001). • The effect of phlebotomy on insulin resistance in a group of patients with non-alcoholic fatty liver disease and strongly elevated ferritin levels found a

controls plus four studies that measured heme-iron intake involving 9246 type 2 diabetics and about 180,000 controls. It was found that for the highest vs. the lowest category of ferritin level, the risk of diabetes was increased 66% in prospective studies and 130% in cross-sectional studies. A similar comparison for heme-iron intake yielded a 31% risk increase. A second study (Bao 2012) examined the association between the risk of diabetes and dietary iron intake in prospective studies. A meta-analysis of five studies gave a pooled relative risk increase of 33% in a comparison of the lowest vs. the highest heme-iron intake. For elevated ferritin levels, they found a 70% increase in relative risk in multivariableadjusted models (seven studies) and a 63% increase in multivariable-adjusted models which included inflammatory markers (five studies). There was no significant association with dietary intake and risk for non-heme or supplemental iron intake, a result consistent with the high bioavailability only of heme iron. Incidentally, another study found a correlation between ferritin levels and the risk of diabetic retinopathy (Canturk 2003). For postmenopausal women (56-62 years of age) who typically have ferritin levels between 70 and 90 ng/dL (Zacharski 2000), data taken from one of the above studies (Bao 2012) for the risk of developing type 2 diabetes are given in the table below according to the highest vs. the lowest ferritin quartiles.

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significant reduction in the HOMA-IR from 4.81 to 3.12 when ferritin levels were reduced from 438 to 52 ng/mL (Valenti 2007). • In a study designed to examine the pathogenesis of diabetes associated with mutations of the hemochromatosis gene, 17 carriers comprising eight patients with diabetes and nine with normal glucose tolerance (NGT) were subjected to phlebotomy and the impact on insulin sensitivity and secretion investigated. Baseline ferritin levels were 942 and 1148 in the NGT and diabetic subjects, respectively. Ferritin targets were ≤ 100 ng/mL or ≤ 50 ng/mL depending of negative or positive evidence for iron deposits in the liver. The target levels were maintained and at 24 months the endpoint parameters measured. In both the NGT and diabetic groups, insulin secretion and insulin sensitivity increased. In the diabetic patients, fasting glucose declined from 137 to 105 mg/dL (7.6 to 5.8 mmol/L), the latter being close to normal (Equitani 2008). • Earlier studies also found that reduction of iron stores consistently produces an improvement in insulin sensitivity and β-cell function (FernandezReal 2002, Fernandez-Real 2005).

Chelation, the Alternative to Phlebotomy or Blood Donation

Advanced glycation end products are thought to play a role in the complications of diabetes and the basic biochemistry involves reactive oxygen species including those attributed to iron activity (Nagai 2012). Oral chelation has been the traditional mainstream approach to iron overload for patients having pathological levels, and several prescription drugs are available. However, iron overloads involved in most of the studies discussed above are nowhere near those encountered in pathological iron overload. Furthermore, while studies, both interventional and observational, suggest target ranges for both men and women, optimum levels are clearly debatable. Chronic low-dose oral chelation therapy may be an important tool for the prevention and treatment of diabetic complications. If one wishes to use non-pharmaceutical interventions to lower ferritin levels to, for example, to the upper end of the normal range for premenopausal women even if one is male, there are a number of “natural” iron chelators. N-acetyl cysteine is in fact a standard therapy for treating pediatric pathological iron overload even in infants. Green tea extract, curcumin, silymarin, alpha-lipoic acid (or

R-lipoic acid) and quercetin all have documented success in iron chelation (Anderson 2012). These chelators also act to eliminate other toxic metals although for mercury it may help to add selenium to N-acetyl cysteine and lipoic acid. Curcumin was recently found to be a very good iron chelator (Jiao 2006). A recent randomized controlled trial demonstrated the effectiveness of curcumin in significantly improving markers of glucose metabolism in diabetics (Chuengsamarn 2012). The results of the Trial to Access Chelation Therapy (TACT), a randomized, placebo controlled intravenous EDTA chelation trial, recently reported. Included were the results that for diabetics, there was a 39% relative risk reduction and a number needed to treat of eight (median follow-up 55 months) found for the composite primary endpoint of total mortality, recurrent MI, stroke, coronary revascularization or hospitalization for angina (Lamas 2013). EDTA chelation generally results in large increases in urine iron immediately post infusion (Cranton 2001). The TACT result is particular interesting since intensive glycemic control with multiple drugs and even the addition of insulin fails to impact cardiovascular or total mortality or almost all other complications associated with diabetics (Boussageon 2012, Hemmingsen 2011, Turnbull 2012, Turnbull 2009). The dramatically lowered fasting blood glucose or HbA1c produced by intensive drug therapy may be viewed as successful control and treatment, but engenders false optimism while the pathogenesis of complications relentlessly progresses to ultimately yield clinical manifestations.

Iron Stores Reductions and Diabetic Complications

Studies on humans are limited. A nine-month study among patients with diabetes using deferiprone oral iron chelation reduced ferritin levels from 144 to 59 ng/mL and decreased the mean albumin/creatinine ratio from 187 to 25 mg/L (Rajapurkar 2013). In addition, a study involving the progression of diabetic nephropathy used a polyphenol–enriched, low-iron carbohydrate-restricted diet over four years. There was no significant change in HbA1c, but there was an absolute decrease in the incidence of serum creatinine doubling of 18% and a decrease in mortality or end-stage kidney disease of 18% over four years (number needed to treat over four years for either was six) (Facchini 2003). Iron chelation due to the polyphenols (from red wine, tea and polyphenol enhanced olive oil) was probably partly responsible for reduced ferritin from 325 to 53 ng/mL and may have been a major contributor to these results.

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Conclusions

Studies are clearly needed to establish optimum iron stores in both men and women in the context of not only diabetes incidence, progression and complications, but also for all inflammation-related chronic diseases, in particular those associated with aging. Furthermore, large clinical studies are needed to examine the impact of lowering iron stores on the incidence of clinical manifestations of the complications of diabetes, not just markers of glucose metabolism. Can aggressive iron stores reduction, perhaps with severe

Can aggressive iron stores reduction, perhaps with severe carbohydrate restriction, cure type 2 diabetes, i.e. eliminate need for any medication? This question should have high priority. carbohydrate restriction, cure type 2 diabetes, i.e. eliminate need for any medication? This question should have high priority. There are health issues associated with iron where one of the potentially effective interventions, blood donation, is free with almost no side effects. Iron stores as measured by ferritin can be dramatically lowered in most individuals without inducing anemia. â&#x2013; References: Anderson, K., 2012. Excess Iron and Brain Degeneration. http://www.lef.org/magazine/mag2012/mar2012_ Excess-Iron-Brain-Degeneration_01.htm. Bao, W., Rong, Y., Rong, S. and Liu, L. Dietary iron intake, body iron stores, and the risk of type 2 diabetes: a systematic review and meta-analysis. BMC Med 2012; 10: 119.

80 www.ihpmagazine.com l September 2013

Boussageon, R., Supper, I., Bejan-Angoulvant, T., Kellou, N., Cucherat, M., Boissel, J.P., Kassai, B., Moreau, A., Gueyffier, F. and Cornu, C. Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials. PLoS Med 2012; 9(4): e1001204. Brewer, G.J. Iron and copper toxicity in diseases of aging, particularly atherosclerosis and Alzheimerâ&#x20AC;&#x2122;s disease. Exp Biol Med (Maywood. ) 2007; 232(2): 323-335. Canturk, Z., Cetinarslan, B., Tarkun, I. and Canturk, N.Z. Serum ferritin levels in poorly- and well-controlled diabetes mellitus. Endocr. Res 2003; 29(3): 299-306. Cho, G.J., Shin, J.H., Yi, K.W., Park, H.T., Kim, T., Hur,J.Y. and Kim,S.H. Serum ferritin levels are associated with metabolic syndrome in postmenopausal women but not in premenopausal women. Menopause. 2011; 18(10): 1120-1124. Chuengsamarn, S., Rattanamongkolgul, S., Luechapudiporn, R., Phisalaphong, C. and Jirawatnotai, S. Curcumin extract for prevention of type 2 diabetes. Diabetes Care 2012; 35(11): 2121-2127. Cranton, E.M., 2001. A Textbook on EDTA Chelation Therapy. Hamptom Roads Publishing Co., Inc., Charlottesville, VA. Depalma, R.G., Hayes, V.W., Chow, B.K., Shamayeva, G., May, P.E. and Zacharski, L.R. Ferritin levels, inflammatory biomarkers, and mortality in peripheral arterial disease: a substudy of the Iron (Fe) and Atherosclerosis Study (FeAST) Trial. J Vasc Surg 2010; 51(6): 1498-1503. Equitani, F., Fernandez-Real, J.M., Menichella, G., Koch, M., Calvani, M., Nobili, V., Mingrone, G. and Manco, M. Bloodletting ameliorates insulin sensitivity and secretion in parallel to reducing liver iron in carriers of HFE gene mutations. Diabetes Care 2008; 31(1): 3-8. Facchini, F.S. and Saylor, K.L. A low-iron-available, polyphenol-enriched, carbohydrate-restricted diet to slow progression of diabetic nephropathy. Diabetes 2003; 52(5): 1204-1209. Fernandez-Real, J.M., Lopez-Bermejo, A. and Ricart, W. Iron stores, blood donation, and insulin sensitivity and secretion. Clin Chem 2005; 51(7): 1201-1205. Fernandez-Real, J.M., Penarroja, G., Castro, A., Garcia-Bragado, F., Hernandez-Aguado, I. and Ricart, W. Blood letting in high-ferritin type 2 diabetes: effects on insulin sensitivity and beta-cell function. Diabetes 2002; 51(4): 1000-1004.

The Journal of IHP

Hemmingsen, B., Lund, S.S., Gluud, C., Vaag, A., Almdal, T., Hemmingsen, C. and Wetterslev, J. Intensive glycaemic control for patients with type 2 diabetes: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. BMJ 2011; 343: d6898. Houschyar, K.S., Ludtke, R., Dobos, G.J., Kalus, U., BroeckerPreuss, M., Rampp, T., Brinkhaus, B. and Michalsen, A. Effects of phlebotomy-induced reduction of body iron stores on metabolic syndrome: results from a randomized clinical trial. BMC Med 2012; 10: 54. Hua, N.W., Stoohs, R.A. and Facchini, F.S. Low iron status and enhanced insulin sensitivity in lacto-ovo vegetarians. Br J Nutr 2001; 86(4): 515-519. Jehn,M., Clark, J.M. and Guallar, E. Serum ferritin and risk of the metabolic syndrome in U.S. adults. Diabetes Care 2004; 27(10): 2422-2428. Jehn,M.L., Guallar, E., Clark, J.M., Couper, D., Duncan, B.B., Ballantyne, C.M., Hoogeveen, R.C., Harris, Z.L. and Pankow, J.S. A prospective study of plasma ferritin level and incident diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Epidemiol 2007; 165(9): 1047-1054. Jiao,Y., Wilkinson, J., Christine, P.E., Buss, J.L., Wang, W., Planalp, R., Torti, F.M. and Torti, S.V. Iron chelation in the biological activity of curcumin. Free Radic Biol Med 2006; 40(7): 1152-1160. Kell, D.B. Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med Genomics 2009; 2: 2. Lamas, G.A., Goertz, C., Boineau, R., Mark, D.B., Rozema, T., Nahin, R.L., Lindblad, L., Lewis, E.F., Drisko, J. and Lee, K.L. Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial. JAMA 2013; 309(12): 1241-1250. Lee, B.K., Kim, Y. and Kim, Y.I. Association of serum ferritin with metabolic syndrome and diabetes mellitus in the South Korean general population according to the Korean National Health and Nutrition Examination Survey 2008. Metabolism 2011; 60(10): 1416-1424. Lee, D.H., Liu, D.Y., Jacobs, D.R., Jr., Shin, H.R., Song, K., Lee, I.K., Kim, B. and Hider, R.C. Common presence of nontransferrin-bound iron among patients with type 2 diabetes. Diabetes Care 2006; 29(5): 1090-1095. Leiva, E., Mujica, V., Sepulveda, P., Guzman, L., Nunez, S., Orrego, R., Palomo, I., Andrews, M. and Arredondo, M.A. High levels of iron status and oxidative stress in patients with metabolic syndrome. Biol Trace Elem. Res 2013; 151(1): 1-8. Micha, R., Michas, G. and Mozaffarian, D. Unprocessed red and processed meats and risk of coronary artery disease and type 2 diabetes--an updated review of the evidence. Curr Atheroscler. Rep 2012; 14(6): 515-524.

Nagai, R., Murray, D.B., Metz, T.O. and Baynes, J.W. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications. Diabetes 2012; 61(3): 549-559. Rajapurkar, M.M., Hegde, U., Bhattacharya, A., Alam, M.G. and Shah, S.V. Effect of deferiprone, an oral iron chelator, in diabetic and non-diabetic glomerular disease. Toxicol Mech Methods 2013; 23(1): 5-10. Rajpathak, S.N., Crandall, J.P., Wylie-Rosett, J., Kabat, G.C., Rohan, T.E. and Hu, F.B. The role of iron in type 2 diabetes in humans. Biochim Biophys Acta 2009; 1790(7): 671-681. Simcox, J.A. and McClain, D.A. Iron and diabetes risk. Cell Metab 2013; 17(3): 329-341. Swaminathan, S., Fonseca, V.A., Alam, M.G. and Shah, S.V. The role of iron in diabetes and its complications. Diabetes Care 2007; 30(7): 1926-1933. Tiedge, M., Lortz, S., Drinkgern, J. and Lenzen, S. Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes 1997; 46(11): 1733-1742. Turnbull, F. and Zoungas, S. Intensive glucose-lowering therapy in people with type 2 diabetes: what do we learn from a new meta-analysis of randomised controlled trials? Evid. Based. Med 2012; 17(3): 98-99. Turnbull, F.M., Abraira, C., Anderson, R.J., Byington, R.P., Chalmers, J.P., Duckworth, W.C., Evans, G.W., Gerstein, H.C., Holman, R.R., Moritz, T.E., Neal, B.C., Ninomiya,T., Patel, A.A., Paul, S.K., Travert, F. and Woodward, M. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 2009; 52(11): 2288-2298. Valenti, L., Fracanzani, A.L., Dongiovanni, P., Bugianesi, E., Marchesini, G., Manzini, P., Vanni, E. and Fargion, S. Iron depletion by phlebotomy improves insulin resistance in patients with nonalcoholic fatty liver disease and hyperferritinemia: evidence from a case-control study. Am J Gastroenterol 2007; 102(6): 1251-1258. Wrede, C.E., Buettner, R., Bollheimer, L.C., Scholmerich, J., Palitzsch, K.D. and Hellerbrand, C. Association between serum ferritin and the insulin resistance syndrome in a representative population. Eur J Endocrinol 2006; 154(2): 333-340. Zacharski, L.R., Ornstein, D.L., Woloshin, S. and Schwartz, L.M. Association of age, sex, and race with body iron stores in adults: analysis of NHANES III data. Am Heart J 2000; 140(1): 98-104. Zacharski, L.R., Shamayeva, G. and Chow, B.K. Effect of controlled reduction of body iron stores on clinical outcomes in peripheral arterial disease. Am Heart J 2011; 162(5): 949-957. Zhao, Z., Li, S., Liu, G., Yan, F., Ma, X., Huang, Z. and Tian, H. Body iron stores and heme-iron intake in relation to risk of type 2 diabetes: a systematic review and meta-analysis. PLoS One 2012; 7(7): e41641.

September 2013 l www.ihpmagazine.com 81

ÂŠiStockphoto.com/luxiangjian4711

successful completion of the questions at the end of this paper has been approved for continuing education by the bddt-n; 1.0 credit parenteral therapy and by the cnpbc; one ce hour.

Mushrooms in Cancer Care

Evidence Reviewâ&#x20AC;&#x201A; By Christopher Habib, ND and Mark Fontes, ND Christopher Habib, ND Clinic Director Mahaya Forest Hill 102-73 Warren Road Toronto, ON M4V 2R9 info@chrishabibnd.com Mark Fontes, ND Naturopathic Doctor Restore Integrative Health Toronto, ON M4M 1K2 mark@restoreyourhealth.ca

82 www.ihpmagazine.com l September 2013

Abstract Mushrooms have been used traditionally in medicine to treat a number of health concerns and recently have been used for the adjunct treatment of various cancers. In particular, Agaricus blazei, Coriolus versicolor, Grifolia frondosa, and Ganoderma lucidum have emerged as common options for patients who are interested in pursuing complementary and alternative medicine. These mushrooms appear to have many effects on the immune system, including the down-regulation of cytokines and TNF-alpha, the stimulation of macrophages and NK cells, and the stimulation of CD4+ and CD8+ cells. Some appear to have direct cytotoxic and anti-angiogenic mechanisms. Mushrooms may even act synergistically to improve conventional cancer treatments. Overall, these immune effects appear to increase overall survival rates and improve quality of life. The evidence behind the use of these four individual mushrooms is explored with a focus on safety, dosage, and clinical expectations.

The Journal of IHP – Continuing Education

Introduction

Many patients with cancer turn to complementary and alternative medicine as an adjunct to their care. Historically, mushrooms have been used across various cultures for their health-promoting effects and for their effects on the immune system (Jin 2012). Much research has been conducted on the effects of mushrooms for various cancer types, including both laboratory research and clinical trials. The most common mushrooms that have been studied are Agaricus blazei, Coriolus versicolor, Grifolia frondosa, and Ganoderma lucidum. Agaricus has immunological effects on the complement and innate immune systems which could potentially lead to pro-apoptotic and anti-angiogenic effects (Lima 2011). Coriolus contains two polysaccharides (PSP and PSK) that appear to improve overall survival rates in patients with multiple cancers, including gastric, colon/ rectal, breast carcinomas (Wong 2012). Grifolia appears to stimulate the function of various immune cells and may improve overall quality of life, reduce tumor burden and act synergistically with chemotherapy, especially in patients with hepatocellular, breast and lung cancer (Kodama 2002). Ganoderma has the potential of reducing tumor burden and stimulating immunity in various cancer types (Jin 2012). This article will individually review the evidence available for these four mushrooms and clearly summarize the most pertinent research findings in the hopes that they can be effectively utilized in a clinical setting. Suggested dosing protocols and safety concerns are also explored for this purpose.

Agaricus blazei

Agaricus blazei is a medicinal mushroom of Brazilian origin. It has been used traditionally to treat a variety of conditions, including diabetes, hypercholesterolemia, chronic hepatitis and cancer (Hetland 2008). Agaricus contains several biologically active constituents, including beta-glucans, which are known activators of macrophages, polymorphonuclear cells and NK cells. The beta-glucans component of Agaricus blazei have been found to be the main source of antitumor activity (Hetland 2008). More recent in-vitro and in-vivo evidence has demonstrated the immunological effects Agaricus blazei can have, via the complement and innate immune systems. A review paper of fourteen studies was recently published to assess Agaricus blazei’s action on the immune system (Lima 2011). In ten of the studies a

stimulatory effect was observed, whereas in one study an inhibitory effect was described. In the remaining three studies, both effects were observed. The inhibitory effects included down-regulation of cytokines IL-2, IL-4, IFN-gamma and TNF-alpha. The stimulatory effects observed included stimulation of macrophages via CD receptors and of NK cells. Furthermore, in-vivo studies reviewed demonstrated a stimulatory effect of antibody synthesis and activation of the complement system. Thus Agaricus blazei’s mechanism of action includes acting as an anti-inflammatory agent, while stimulating both innate and adaptive immunity (Lima 2011). Furthermore, a phase I clinical study of Agaricus blazei was conducted on seventy-eight patients with a history of cancer who were in remission (Ohno 2011). Adverse events (AE’s) were observed in 12% of patients studied, with reports of nausea being the most common. Importantly, the authors make note that none of the AE’s occurred in a dose-dependent manner and that Agaricus blazei is considered safe in this patient population. Most of the anti-cancer research for Agaricus blazei consists of in-vitro and in-vivo studies. A pro-apoptotic effect has been observed in-vitro and whether this effect is maintained in human studies remains to be seen. Anti-angiogenic effects have also been studied in a rat model (Kimura 2004). Further human trials for Agaricus blazei are needed to fully understand its utility and safety. Dosage: 1,500-3,000mg of hot-water extract daily, containing a minimum of 40% polysaccharides. Safety: Caution with patients diagnosed with an autoimmune condition, and/or using immunosuppressive medications. Study

Cancer / Cell Type

Results

Wu 2012; in-vitro

Osteosarcoma

Induction of apoptosis.

Akiyama 2011; in-vitro

Leukemia

Induction of apoptosis via caspase activation.

Lee 2011; in-vitro

Hepatocellular

Enhances doxorubicininduced apoptosis.

Su 2011; in-vitro

Hepatocellular

Induction of apoptosis.

Yu 2009; in-vitro and in-vivo

Prostate

Anti-proliferative and anti-angiogenic effects.

September 2013 l www.ihpmagazine.com 83

Coriolus versicolor (Trametes versicolor)

The mushroom Coriolus versicolor (Trametes versicolor) is a macrofungi belonging to the Basidiomycetes class, which consists of at least 22,000 known species (Chu 2002). Traditionally, it has been used to increase energy and treat pulmonary and upper respiratory tract infections, hepatitis and cancer. The fruiting body and mycelium provides its most effective components (Wong 2012).

Coriolus versicolor is one of the better-studied mushroomsâ&#x20AC;&#x2030;â&#x20AC;Ś Coriolus contains several different polysaccharides, however, most research has focused on polysaccharide peptide (PSP) and polysaccharide krestin (PSK) (Ng 1998). PSP and PSK are two chemically similar structures isolated from Coriolus versicolor from the mycelia of two different strains. Both extracts consist of similar compounds, with PSK predominantly containing fucose while PSP contains arabinose and rhamnose (Ng 1998). Coriolus versicolor is one of the better-studied mushrooms, with several randomized control trials. Most of the research is focused on quality of life outcomes and its use adjunctively with conventional cancer treatments. PSP and PSK are both used as interventions, however, PSK is more commonly used in randomized control trials. A systematic review and meta-analysis was conducted to assess the efficacy of Coriolus versicolor on overall survival in patients with cancer (Wong 2012). Thirteen randomized trials were included. Types of cancer (encompassing stage I to IV) in these studies included esophageal, gastric, colon/rectal, breast and nasopharyngeal carcinoma. All of the trials compared Coriolus versicolor with conventional cancer treatment versus conventional cancer treatment alone (with or without placebo). The dose range was 1-3.6g daily, and the duration of therapy was 1-36 months. In total, 1,284 patients with cancer were studied who received Coriolus versicolor versus 1,303 in the conventional cancer treatment group. There was a statistically significant difference in overall survival at 5 year (P < 0.00001; RR = 1.14 95% CI = 1.09, 1.20). AEâ&#x20AC;&#x2122;s were 84 www.ihpmagazine.com l September 2013

not significantly increased as a result of Coriolus versicolor intervention. Of patients randomized to Coriolus versicolor, there was a 9% absolute reduction in 5-year mortality, resulting in one additional patient alive for every 11 patients treated. The authors state that in patients with breast, gastric, or colorectal cancer treated with conventional cancer treatments and Coriolus versicolor, the overall 5-year survival rate was more profound (Wong 2012). Dosage: 3,000-6,000 mg of hot-water extract daily, containing a minimum of 20-40% beta-glucans. Safety: Caution with patients diagnosed with an autoimmune condition, and/or using immunosuppressive medications.

Study

Tanaka 2012; RCT

Cancer / Cell Type

Gastric

Extract Used

Results

PSK

In patients with early tumor recurrence, overall survival was significantly better in the PSK group. In patients with lymph node metastasis, median overall survival was better in the PSK group compared with the control group.

Shibata 2011; RCT

Metastatic colorectal

PSK

PSK + FOLFOX chemotherapy resulted in lower frequencies of adverse effects (nausea, peripheral neuropathy, neutropenia).

Yoshikawa 2011; RCT

Advanced or recurrent PSK gastric

Improved overall survival vs control.

Tsang 2003; Advanced RCT NSCLC

Ohwada 2001; RCT

Stage II or III colorectal

PSP

Significant improvement in WBC and neutrophil counts; slowed disease progression.

PSK

Improved disease-free survival, overall survival at 3 years; prevented metastases vs control.

The Journal of IHP – Continuing Education Maitake (Grifola frondosa)

Maitake mushroom consists of a beta-glucan termed D-Fraction, which is extracted from the fruiting body (Kodama 2003). D-Fraction has been found to stimulate the function of immune cells such as macrophages, helper T cells, cytotoxic T cells and NK cells (Kodama 2003). Case series reports and clinical trials have reported an immune-stimulatory effect from Maitake mushroom, showing an increase in CD4+ cell count after administration (Kodama 2002). Furthermore, Maitake may improve overall quality of life, reduce tumor burden and act synergistically with chemotherapy. These effects were most profound in patients with hepatocellular, breast and lung cancer (Kodama 2002). A phase I/II clinical study of Maitake mushroom was conducted on thirty-four postmenopausal breast cancer patients, free of disease after initial treatment, to detect immunological effects (Deng 2009). The authors state that no dose-limiting toxicity was encountered and that there appears to be no ‘maximum dose’, only ‘optimal dose’ depending on the immunological outcome desired. Some of the parameters measured increased with an increasing Maitake dose (CD4+ and CD8+ cells), whereas others were highest at an intermediate dose of Maitake (IL-10, IL-2, TNF-alpha) (Deng 2009). There is a complex interaction of Maitake mushroom with the innate and adaptive immune system. Depending on the dose, there can be specific immune stimulatory and/or immune suppressing effects. Preliminary evidence also suggests that intravenous vitamin C may act synergistically with Maitake D-Fraction to improve conventional cancer treatments (Konno 2009). Dosage: 500-3,000 mg of hot-water extract daily, containing a minimum of 20% polysaccharides. Safety: Caution with patients diagnosed with an autoimmune condition, and/or using immunosuppressive medications. Study

Cancer / Cell Type

Results

Reishi (Ganoderma lucidum)

Ganoderma lucidum has been used to treat a variety of conditions for centuries in China, Korea and Japan (Sliva 2003). Traditionally, it has been used to treat hypertension, hyperlipidemia, viral infections, cardiovascular disease, asthma and cancer (Sliva 2003). The direct cytotoxic and anti-angiogenesis mechanisms of Ganoderma lucidum have been reproducibly demonstrated by in-vitro studies (Yuen 2005). Human clinical studies are required in order to better establish proper dosing and define the full range of activity of Ganoderma lucidum and its mechanisms of actions. The evidence available is conflicting and there are specific safety concerns with Ganoderma. A recent Cochrane review did not find sufficient evidence to justify the use of Ganoderma lucidum as a first-line treatment for cancer (Jin 2012). However, the authors state that there is sufficient evidence to consider Ganoderma lucidum as an adjunctive treatment to conventional cancer therapies due to its potential of reducing tumor burden and stimulating immunity. Importantly, no major toxicity was noted in the studies reviewed with only a few reports of minor adverse events. There is concern that Ganoderma lucidum may inhibit platelet aggregation and is a relative contraindication for patients on antiplatelet medication (Tao 1990). Evidence is currently conflicting, with studies stating that at doses of 1.5g Ganoderma lucidum does not impair hemostatic function and increase risk of bleeding (Kwok 2005). However, at higher doses hemostatic function may be impaired and currently, caution is advised. Dosage: 1000-4000 mg of hot water extract daily, containing a minimum of 10% polysaccharides. Safety: Caution with patients diagnosed with an autoimmune condition, and/or using immunosuppressive medications. Caution is also advised for patients on concomitant hypotensive and/ or antiplatelet therapy. Study

Cancer / Cell Type

Results

Lee 2010; in-vitro

Colon

Improves inflammation by reducing TNF-alpha and its signaling through NF-kappaB.

Lee 2010; in-vitro

Colon

Improves inflammation by reducing TNF-alpha and its signaling through NF-kappaB.

Louie 2010; in-vitro

Bladder

D-Fraction acted synergistically with interferon treatment to trigger apoptosis.

Louie 2010; in-vitro

Bladder

D-Fraction acted synergistically with interferon treatment to trigger apoptosis.

Kodama 2003; human trial

Lung, Breast, Gastric and Liver

D-Fraction modestly increased CD4+ and CD8+ cell numbers, and significantly increased NK cell numbers after administration.

Kodama 2003; human trial

Lung, Breast, Gastric and Liver

D-Fraction modestly increased CD4+ and CD8+ cell numbers, and significantly increased NK cell numbers after administration.

Matsui, 2001; in-vitro

Not applicable

D-Fraction significantly increased plasma vascular endothelial growth factor (VEGF) concentration.

Matsui, 2001; in-vitro

Not applicable

D-Fraction significantly increased plasma vascular endothelial growth factor (VEGF) concentration.

September 2013 l www.ihpmagazine.com 85

Conclusion

Many patients with cancer use complementary and alternative medicine as an adjunct to their care, including the use of mushrooms. Many immunological mechanisms were described. In terms of outcomes, Agaricus was shown to induce apoptosis in a number of cancer types. In clinical trials of patients with remission, it had a good safety profile with a limited number of AE’s (Ohno 2011). Coriolus is the most well-studied mushroom and in studies

The evidence supports the use of mushrooms as clinically useful adjuncts to conventional cancer care, especially Coriolus versicolor. of 5 cancer types showed a 9% absolute reduction in 5-year mortality, resulting in one additional patient alive for every 11 patients treated (Wong 2012). Grifolia was shown to stimulate various immune cells, but had limited data with regards to patient outcomes. Ganoderma had some conflicting evidence regarding its clinical effects and had potential safety concerns due to the potential inhibition of platelet aggregation (Kwok 2005). Overall, mushrooms should be used in doses of 500-6,000mg per day, with some variation based on the specific mushroom. Additional precautions should be taken in patients diagnosed with an autoimmune condition or using immunosuppressive medications. The evidence supports the use of mushrooms as clinically useful adjuncts to conventional cancer care, especially Coriolus versicolor. ■

Chu K, Ho S, Chow A. Coriolus versicolor: A Medicinal Mushroom with Promising Immunotherapeutic Values. Journal of Clinical Pharmacology. 2002;42:976-984. Deng G, Lin H, Seidman A, Fornier M, D’Andrea G, Wesa K, Yeung S, CunninghamRundles-S, Vickers A, Cassileth B. A phase I/ II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients: immunological effects. J Cancer Res Clin Oncol. 2009;135:1215-1221. Hetland G, Johnson E, Lyberg T, Bernardshaw S, Tryggestad A, Grinde B. Effects of the Medicinal Mushroom Agaricus blazei Murill on Immunity, Infection and Cancer. Scandinavian Journal of Immunology. 2008 July;68:363-370. Jin X, Ruiz J, Sze DMY, Chan GCF. Ganoderma lucidum (Reishi mushroom) for cancer treatment (Review). The Cochrane Collaboration. 2012;6:1-38. Kimura Y, Kido T, Takaku T, Sumiyoshi M, Baba K. Isolation of an anti-angiogenic substance from Agaricus blazei Murill: its antitumor and antimetastatic actions. Cancer Sci. 2004 Sept;95(9):758-64. Kodama N, Komuta K, Nanba H. Can Maitake MD-Fraction Aid Cancer Patients? Alternative Medicine Review. 2002;7(3):236-9. Kodama N, Komuta K, Nanba H. Effect of Maitake (Grifola frondosa) D-Fraction on the Activation of NK cells in Cancer Patients. J Med Food. 2003;6(4):371-77. Konno S. Synergistic potentiation of D-Fraction with vitamin C as possible alternative approach for cancer therapy. Int J Gen Med. 2009 Jul;2:91-108.

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The Journal of IHP â&#x20AC;&#x201C; Continuing Education

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Roppongi T, Takahashi T, Nakamura S, Kawashima Y, Nakajima T, Morishita Y. Adjuvant Therapy With Protein-Bound Polysaccharide K and Tegafur Uracil in Patients with Stage II or II Colorectal

Cancer: Randomized, Controlled Trial. Dis Colon Rectum. 2003 Aug;46(8):1060-8. Oka S, Tanaka S, Yoshida S, Hiyama T, Ueno Y, Ito M, Kitadai Y, Yoshihara M, Chayama K. A water-soluble extract from culture medium of Ganoderma lucidum mycelia suppresses the development of colorectal adenomas. Hiroshima J Med Sci. 2010 Mar;59(1):1-6. Shibata M, Shimura T, Nishina Y, Gonda K, Matsuo S, Abe H, Yajima Y, Nakamura I, Ohki S, Takenoshita S. PSK decreased FOLFOX4-induced peripheral neuropathy and bone marrow suppression in patients with metastatic colorectal cancer. Gan To Kagaku Ryoho. 2011 May;38(5):797-801. Sliva D. Ganoderma lucidum (Reishi) in Cancer Treatment. Int Cancer Therapies. 2003;2(4):358-364.

Tao J, Feng KY. Experimental and clinical studies on inhibitory effect of ganoderma lucidum on platelet aggregation. J Tongji Med Univ. 1990;10:240-3. Thyagarajan A, Zhu J, Sliva D. Combined effect of green tea and Ganoderma lucidum on invasive behavior of breast cancer cells. Int J Oncol. 2007 Apr;30(4):963-9. Tsang KW, Lam CL, Mak JC, Ooi GC, Ho JC, Lam B, Man R, Shan JS, Lam WK. Coriolus versicolor polysaccharide peptide slows progression of advanced non-small cell lung cancer. Respir Med. 2003 Jun;97(6):618-24. Weng CJ, Chau CF, Yen GC, Liao JW, Chen DH, Chen KD. Inhibitory effects of ganoderma lucidum on tumorigenesis and metastasis of human hepatoma cells in cells and animal models. J Agric Food Chem. 2009 Jun;57(11):5049-57. Wong E, Fai C, Chung L. Efficacy of Yun Zhi (Coriolus versicolor) on Survival in Cancer Patients: Systematic Review and Meta-Analysis. Recent Patents on Inflammation and Allergy Drug Discovery. 2012;6:78-87. Wu B, Cui J, Zhang C, Li Z. A polysaccharide from Agaricus blazei inhibits proliferation and promotes apoptosis of osteosarcoma cells. Int J Biol Macromol. 2012 May; 50(4): 1116-20. Yoshikawa T, Tsuburaya A, Saze Z, Aoyama T, Hasegawa S, Kanemoto A, Terashima M, Tahara H. Randomized phase II trial to compare S-1 and S-1/PSK for advanced or recurrent gastric cancer-lessons from the results. Gan To Kagaku Ryoho. 2011 Nov;38(12):1909-11. Yu CH, Kan SF, Shu CH, Lu TJ, Sun-Hwang L, Wang PS. Inhibitory mechanisms of Agaricus blazei Murill on the growth of prostate cancer in vitro and in vivo. J Nutr Biochem. 2009 Oct; 20(10):753-64. Yuen J, Gohel M. Anticancer Effects of Ganoderma lucidum: A Review of Scientific Evidence. Nutrition and Cancer. 2005;53(1):11-17. Zhao S, Ye G, Fu G, Cheng JX, Yang BB, Peng C. Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin. Int J Oncol. 2011 May;38(5):1319-27.

September 2013 l www.ihpmagazine.com 87

Questions 1. C oriolus versicolor is one of the four well-researched mushrooms described in this paper. It contains two polysaccharides called: a) Arabinoxylan and chitin b) Ribose and diribose c) PSK and PSP d) None of the above 2. A review paper summarized 14 studies of Agaricus blazeiâ&#x20AC;&#x2122;s effects on the immune system. They included which of the following? a) Immune stimulatory effect in 10 studies b) Immune inhibitory effect in one study c) Both stimulatory and inhibitory effects in 3 studies d) All of the above 3. Agaricus stimulates adaptive but not innate immunity. a) True b) False 4. Which of the following is NOT true about Coriolus versicolor? a ) It also known as Trametes versicolor b) I t is traditionally used to treat pulmonary and upper respiratory tract infections, and hepatitis c) It is traditionally used to treat Alzheimerâ&#x20AC;&#x2122;s disease d) All of the above 5. A 2012 meta analysis by Wong examined the effect of Coriolus on overall survival among cancer patients. Compared with conventional care alone, the combination of Coriolus plus conventional care showed which of the following? a) 6% absolute risk reduction in 5 year mortality b) 9% absolute risk reduction in 5 year mortality c) 15% absolute risk reduction in 5 year mortality d) 21% absolute risk reduction in 5 year mortality

6. T he beta glucan extract of Grifola frondosa, known as the R-Fraction, has been the best studied form of this mushroom. a) True b) False 7. Clinical evidence shows that Grifola (Maitake) may have which of the following effects on immune parameters? a) Increased CD+4 and CD+8 counts b) Increased TNF-alpha c) Decreased TNF-alpha d) A and C 8. A 2012 Cochrane review reported that there is not sufficient evidence to support using Reishi (Ganoderma) as a first line anticancer therapy. Nonetheless, the review also concluded that there is sufficient evidence to support using Reishi as an adjunctive treatment due to its antitumor and immune effects. a) True b) False 9. Which of the following constitutes a potential safety concern with use of Ganoderma? a) Concurrent use of antiplatelet/ anticoagulant medications b) Concurrent use of anti-estrogen therapy such as tamoxifen c) Concurrent radiation therapy d) All of the above he most effective form of mushrooms to use is a hot water 10. T extract standardized to polysaccharide content. a) True b) False

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fast joint care+

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, sulftated 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; this underscores 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. New research now indicates that fast joint care+ is also an effective treatment for non arthritic joint pain and fibromyalgia. 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). 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. Direct average annual per person medical expenditures due to arthritis ranged from $1454- 2206 (Theis 2007). 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) Non Arthritic Joint Pain In addition to studies on NEM, fast joint care+ as a whole has been specifically assessed in subjects with non arthritic joint pain. In a randomized study, 60 unmedicated subjects with chronic (but non-arthritic) joint pain were given either 500mg of fast joint care+ or placebo for one month. Those in the fast joint care+ group reported a reduction in post-exercise pain ratings, with four times less pain than the placebo group (Berardi, unpublished data). This exciting finding shows that fast joint care+ is an effective therapy for those “weekend warriors” suffering from joint pain, and not exclusively for those suffering from osteoarthritis. Fibromyalgia An open-label pilot study supervised by Toronto area fibromyalgia specialist Alison Bested, MD investigated the effects of 500mg of fast joint care+ among 15 patients when given daily for eight weeks. Outcomes were measured using the Fibromyalgia Impact Questionnaire (FIQ) and Brief Pain Inventory (BPI) scales before and at the conclusion of the study. Results showed that fast joint care+ significantly improved sleep, pain while working (i.e. performing activities), and overall pain ratings in FM. “Enjoyment of Life”, “Everyday Work” and “Missed Work” scales also trended towards improvement (Bested, unpublished data) Recommended Use 500 mg or one capsule per day. Contraindicated in persons with allergy to egg or egg products. No known adverse effects. References Berardi J. Egg Shell Membrane Reduces Joint Pain. Unpublished data. Bested A. Summary of a pilot, open-label, study of eggshell membrane (fast joint care+) in fibromyalgia patients. Completed April 2012. Unpublished data. 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.

Nutritional Fundamentals for Health Inositol SAP Myo-inositol powder for the treatment of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common cause of ovulatory disorders and female infertility. Signs and symptoms of PCOS may include anovulation or menstrual irregularities; ovarian cysts on ultrasound; hyperandrogenism including hirsutism, acne and alopecia; insulin resistance; and obesity. Insulin resistance and secondary hyperinsulinemia appear to play a causative role in the development of PCOS. myo-Inositol has been suggested as a first-line therapy in the treatment of PCOS, and has been shown to be effective in mitigating the symptoms of this syndrome and its associated comorbidities.

ACTIVE INGREDIENTS

Each scoop contains: Inositol (myo-inositol) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 g Contains no: Preservatives, allergens, artificial flavor or color, sweeteners, wheat, gluten, soy, starch, yeast, citrus, egg or dairy.

DOSAGE

Adults: Mix 1 scoop to 8 oz. (250 ml) of water or juice one to three times daily mixed into juice or water or as directed by your health care practitioner. Consult a health care practitioner for use beyond 6 weeks.

INDICATIONS

Inositol SAP may be effective in the treatment of PCOS and its related morbidities—including hypercholesterolemia, hyperandrogenemia, hyperinsulinemia, hirsutism, acne, and menstrual irregularity—, and in the restoration of ovarian activity and infertility.

SAFETY

myo-Inositol is generally well-tolerated. At therapeutic doses up to 4 g/d, no significant adverse events have been reported for the oral supplementation of myo-inositol in studies for up to 6 months.

PURITY AND CLEANLINESS

Third-party testing is performed on finished product to ensure Inositol SAP is free of heavy metals, pesticides, solvents and other impurities.

Flora SAP

Science-based suppository probiotic for vaginal health Genitourinary infections affect more than 1 billion women worldwide every year and are the most common reason a women will see a gynecologist. These infections can be bacterial in nature (bacterial vaginosis) or fungal in nature (vulvovaginal candidiasis). The types of bacteria in the vaginal canal will fluctuate based on a variety of factors including hormone levels, diet, sexual contact and douching; however, the basic composition is Lactobacilli-dominant in healthy females. It is the depletion of these healthy organisms that can leave a woman prone to urinary and vaginal infections. There are probiotic bacteria that can help in modulating the immune system and displacing pathogens that can cause these infections. A healthy vaginal canal should be colonized by Lactobacilli as the dominant bacterial species. Lactobacilli produce H2O2, which helps maintain a vaginal pH close to 4.0, which is essential for vaginal health. Maintenance of a vaginal pH around 4.0 decreases a woman’s risk of developing vaginosis.

ACTIVE INGREDIENTS

Each suppository capsule contains: Lactobacillus rhamnosus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 billion Lactobacillus acidophilus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 billion Lactobacillus fermentum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 billion Lactobacillus casei . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 million Streptococcus salivarius ssp. thermophilus . . . . . . . . . . . . . . . . 50 million Contains no: Preservatives, artificial flavor or color, sugar, starch, wheat, gluten, corn or yeast. Contains 10 capsules per bottle and applicator. Keep refrigerated.

DOSAGE

Insert 1 capsule daily deep in the vagina before bedtime or as directed by your health care practitioner. Use for ten (10) days. ɶ ɶ ɶ ɶ

INDICATIONS

Flora SAP can help prevent and treat recurrent vulvovaginal candidiasis and bacterial vaginosis. Flora SAP may help prevent growth of Group-B streptococci (GBS) during pregnancy. Flora SAP can be used to help prevent spontaneous preterm delivery associated with intrauterine infection. Flora SAP can be used to help prevent recurrent urinary tract infections.

SAFETY

Lactobacilli are considered to be safe because they are components of the commensal human flora and due to the fact that they have been used for a long time in food industry and in douches, even by pregnant women, without harmful effects.

PURITY, CLEANLINESS AND STABILITY

Third-party testing is performed on finished product to ensure Flora SAP is free of heavy metals, pesticides, volatile organics and other impurities.

Scientific Advisory Panel (SAP): adding nutraceutical research to achieve optimum health 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

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Presents

Advances in

Women’s Health $40/practitioners • $20/students Pre-approved for CE credits Lunch will be provided Free products and samples

Toronto | October 5, 2013, CCNM, 9:00am–4:30pm Dr. Tori Hudson, ND

Women’s Health Research Update: Natural Therapies & Controversial Issues

Dr. Heidi Fritz, MA, ND

NHPs in Pregnancy: Improving Health Outcomes of the Next Generation

Dr. Tracy Malone, ND

Integrative Fertility Care: Preconception to Pregnancy

Dr. Tori Hudson, ND

Challenging Cases in Women’s Health: PCOS, Endometriosis, Interstitial Cystisis

Vancouver | November 16, 2013, Hyatt Regency, 9:00am–4:30pm Dr. Tori Hudson, ND

Women’s Health Research Update: Natural Therapies & Controversial Issues

Dr. Alana Shaw, MSc (c.), ND

Fertility & Aging: Exposing the Myths & Misconceptions

Dr. Cathy Carlson-Rink, ND, RM

Postpartum Care: Healing Traditions from Around the World

Dr. Tori Hudson, ND

Challenging Cases in Women’s Health: PCOS, Endometriosis, Interstitial Cystisis

To register contact 1 866 510-3123 or info@nfh.ca — Limited space available

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Get back to doing the things you

love to do

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. • Fast acting, research proven – Natural Eggshell Membrane starts reducing joint pain in as little as 7 days** • Effective – Research shows Natural Eggshell Membrane provides up to 5 times better results than other natural health products including Glucosamine, and often better results than Rx products • Complete joint care –Natural Eggshell Membrane provides important nutrients, including collagen for joint repair, to help build cartilage, reduce inflammation, and increase range of motion *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, chondroitin and hyaluronic acid and Type 1 collagen – all essential nutrients for proper joint health and flexibility. **Clinical Intervention in Aging 2009; 4:235-40

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