IHP October 2014

clinic profile

NATURAL HEALTH PRODUCTS IN IBD

By Jordan Robertson, ND, et al.

HEALTH BENEFITS OF GREEN SPACES

By Elizabeth Stavros, ND, and Jenny Yuhkt, ND

NATURAL HEALTH PRODUCTS IN DEMENTIA

PM42684014 | 1235 BAY STREET SUITE 400 | TORONTO ONTARIO, M5R 3K4 | $14.95

By Ronald Reichert, ND

Dr Howard Libstug, DDS Holistic dentistry since before the term existed

Continuing Education Metformin for cancer treatment

By Maria Shapoval, ND, and Heidi Fritz, MA, ND WWW.IHPMAGAZINE.COM 1

www.ihpmagazine.com | June/July 2014

OCTOBER 2014

Support the Immune System with Cor Defence

GENESTRA BRANDS Cor Defence contains Epicor®: a proprietary nutrient combination produced naturally from Saccharomyces cerevisiae yeast. Also includes European elderberry flower extract, vitamin C, zinc, and vitamin D for additional antioxidant protection and immune support. Cor Defense is a maintenance product available in a convenient once daily capsule format.

EGETARIAN

• Clinically proven to reduce the incidence of cold and flu symptoms • Helps to maintain immune function • An antioxidant for the maintenance of good health

CANADA: 1-800-2635861 | www.seroyal.com

GENESTRA BRANDS COR DEFENCE PRODUCT MONOGRAPH Genestra Brands Cor Defence contains Epicor®, a proprietary nutrient extract from Saccharomyces cerevisiae yeast that is clinically proven to help maintain immune function. Cor Defence also includes European elderberry flower extract, vitamin C, zinc and vitamin D for additional antioxidant protection and immune support.

The proprietary fermentation process used in the production of EpiCor stresses yeast cells to increase the concentration of bioactive components, including yeast glucans (beta-1-3-glucan and beta-1-6 glucan), polyphenols and vitamins and minerals1.

In vitro EpiCor studies have demonstrated anti-inflammatory effects, such as the stimulation of B lymphocytes and natural killer cells2. In a placebo-controlled clinical trial of 12 healthy participants, topical application of EpiCor significantly reduced inflammatory response and subjective skin irritation ratings induced by a histamine skin prick1. In a randomised, double-blind, placebo-controlled clinical trial of 116 healthy participants not vaccinated with the influenza vaccine, daily supplementation EpiCor significantly reduced both the incidence and duration of cold and flu-like symptoms. Participants were randomised to receive either 500 mg of EpiCor or a placebo treatment daily for 12 weeks. Compared with placebo treatment, participants in the EpiCor treatment group experienced a significant reduction in self-recorded duration and occurrence of flu and cold-like symptoms (including headache, fatigue, general aches and pains, weakness, sore throat, cough, nasal stuffiness, and other symptoms)3.

Elder flower and its extracts have a history of traditional use for the relief of early symptoms of common cold4. Zinc helps to maintain immune function and maintain healthy skin5. Vitamin C may help to prevent and relieve cold and flu symptoms. A controlled study evaluated the effects of a megadose of vitamin C in the prevention and relief cold and flu symptoms in 252 test and 463 control participants. Participants in the control group that experienced cold or flu symptoms were treated with conventional medications (pain relievers and decongestants), while participants in the treatment group were treated with hourly 1000 mg doses of vitamin C for the first 6 hours and then 3 times daily afterwards. The treatment group experienced an 85% decrease in overall reported flu and cold symptoms after vitamin C supplementation6.

EACH CAPSULE CONTAINS:

Bakers Yeast (Saccharomyces cerevisiae) (EpiCor®*) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 500 European Elderberry (Sambucus nigra) Flower Extract (4:1) . . . . . . . . . . . . . . . . . . . . . . . . . 75 300 mg Dried Equivalent Vitamin C (ascorbic acid) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Zinc (zinc monomethionine) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 Vitamin D (cholecalciferol) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 .25 mcg / 50

mg mg mg mg IU

Non-Medicinal Ingredients: Hypromellose, cellulose, magnesium stearate, silica * EpiCor® is a registered trademark of Embria Health Sciences, L .L .C .

Recommended Adult Dose: Take one capsule daily with food, a few hours before or after taking other medications, or as recommended by your healthcare practitioner .

Product Size: 30 Vegetable Capsules

EGETARIAN

1. Jensen G, Carter S, Reeves S, Robinson L, and Benson K. Anti-Inflammatory Properties of a Dried Fermentate In Vitro and In Vivo. Journal of Medicinal Food. 2014; 00(0): 1-7 2. Jensen G, Hart N, and Schauss G. An anti-inflammatory immunogen from yeast culture induces activation and alters chemokine receptor expression on human natural killer cells and B lymphocytes in vitro. Nutrition Research. 2007; 27: 327-335 3. Moyad MA, Robinson LE, Zawada ET Jr, Kittelsrud JM, Chen DG, Reeves SG, Weaver SE. Effects of a modified yeast supplement on cold/flu symptoms. Urol Nurs. 2008 Feb;28(1):50-5.

4. Blumenthal M, Busse W, Goldberg A, Gruenwald J, Hall T, Riggins C, Rister R. The Complete German Commission E Monographs – Therapeutic Guide to Herbal Medicines. American Botanical Council and Integrative Medicine Communications. Boston, MA: USA; 1998.

5. NHPD Monograph on Zinc (from non-picolinate sources). 2014-03-24 6. Gorton HC, Jarvis K. The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections. J Manipulative Physiol Ther. 1999 Oct;22(8):530-3. Copy for IHP Cor Defence

C ANADA: (800) 263-5861 | www.seroyal.com

from the publisher

NPN’s in full swing As fall settles in we are very excited to see how all the effort and hard work of the year has paid off! NPN’s are now in full force which hopefully will mean a level playing field for Canadian manufactures and importers. Thank you to all those involved in shaping the NPN program into something functional... Unlike many people feared, the diversity of products remains strong, and creativity can now flourish as everyone finally has a good understanding of what the rules are. I hope practitioners across the country recognize that Canadian Retailers, Canadian Manufactures, the Canadian Health Food Association, Canadian Importers & Distributors have all done their part in shaping the NPN program!

Where we are today represents a lot of hard work... IHP is very grateful to the advertisers that support IHP as they have gone through all that was required by Health Canada to meet their requirements.

An emerging and growing problem is the realization that many people are importing products from unlicensed countries for personal use. NPN registration has truly raised the bar of what constitutes a natural health product... The products people are importing have no guarantees of active ingredient identification, quantities of ingredients, and no review of safety and efficacy. More often than not, these products fail to deliver desired results! In the end, it creates a bad image for the entire industry as people fail to achieve the outcomes they expected. The consumer does not realize the difference between product with or without an NPN, they simply feel they tried a natural product and it didn’t work.

Sanjiv Jagota Publisher

Connect With Us

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Sanjiv founded Nature’s Source Natural Dispensary in 1998, and soon after started IHP Magazine in order to pull together all of his experience in the health and wellness industry, as well as to create a way to help connect resources and information to experts working in the field. Sanjiv has a background in organic chemistry and biochemistry, and also conducted research in the pharmaceutical industry. Nature's Source works closely with medical doctors, naturopathic doctors, chiropractors, homeopathic practitioners, personal trainers and nutritionists to take care of people searching for preventative health strategies and illness recovery solutions. Nature's Source offers a wide selection of supplement brands and specialty products, including professional lines, sports nutrition, homeopathics, and natural health and beauty products. All products are high-quality, evidence-based, and tested by third-parties for compliance. For more information, please visit www.natures-source.com.

www.ihpmagazine.com | October 2014

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Products Professionals Prefer®

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• Liquid tinctures dried to powder form in a benign, low heat process

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Product Monograph for IHP, October 2014

Bio-Ferra 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 | Scott Jordan (416) 203-7900 ext. 6106 Production Manager | Erin Booth (416) 203-7900 ext. 6110 Junior Designer | Tamara Kelly

™

• An innovative liquid polysaccharide-iron complex • Bio-FerraTM can rapidly replete iron deficiencies and is an ideal supplement to a vegan/vegetarian diet • With a pleasant-tasting natural green apple flavor, Bio-FerraTM is well tolerated and easily incorporated into daily routine

Contributors Philip Rouchotas, MSc, ND Christopher Habib, ND,

President | Olivier Felicio (416) 203-7900 ext. 6107 Controller & Operations | Melanie Seth

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 Erin Poredos | Tel: (416) 203-7900 ext 6128 Email: erin@gorgmgo.com Circulation Rive Gauche Media 1235 Bay St, Suite 400 Toronto, Ontario, M5R 3K4 Email: circulation@ihpmagazine.com

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Published by IHP Magazine

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The publisher is not liable to any advertiser for any misprints in advertising not the fault of the publisher and in such an event the limit of the publisher’s liability shall not exceed the amount of the publisher’s charge for such advertising. No portion of this publication may be reproduced, in all or part, without the express written permission of the publisher.

The liquid lement iron suppoctors that d een have b for! searching

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ihp magazine is pleased to review unsolicited submissions for editorial consideration under the following conditions: all material submitted for editorial consideration (photographs, illustrations, written text in electronic or hard copy format) may be used by ihr Media Inc. and their affiliates for editorial purposes in any media (whether printed, 0electronic, internet, disc, etc.) without the consent of, or the payment of compensation to, the party providing such material. Please direct submissions to the Editor, ihp magazine.

1 866 783-7504 www.cyto-matrix.com

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contents

This Issue: October 2014 • Vol. 7 • No. 5

33 Dr Howard Libstug and Associates Cover Story

Holistic dentistry since before the term existed

41 Naturopathic Foundations Health Clinic Clinic Profile Treating the cause

47

The Journal of IHP Peer-reviewed articles on clinically revelant topics

Coming Next Issue Meditation and gene expression

Departments

4 Publisher’s Letter 11 Research News 19 Industry News 24 Calendar 25 Product Profiles 48 Editor’s Letter 50 Peer Review Board 52 Editorial Board 74 Continuing Education

Applying genomics testing in clinical practice Melatonin in oncology Cover Photograph by Eric Forget 8

www.ihpmagazine.com | October 2014

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research news Organically grown crops and antioxidant content: systematic review and meta-analysis

Probiotics and blood pressure: systematic review and meta-analysis This systematic review clarified the effects of probiotic supplementation on blood pressure. PubMed, Scopus, Cochrane Library (Central), Physiotherapy Evidence Database, and Clinicaltrial. gov databases were searched until January 2014 to identify eligible articles.

Meta-analysis using a random-effects model was chosen to analyze the impact of combined trials. Nine trials were included. The results showed that probiotic consumption significantly changed systolic BP by -3.56 mm Hg (95% confidence interval, -6.46 to -0.66) and diastolic BP by -2.38 mm Hg (95% confidence interval, -2.38 to -0.93) compared with control groups. A greater reduction was found with multiple as compared with single species of probiotics, for both systolic and diastolic BP. Subgroup analysis of trials with baseline BP ≥130/85 mm Hg compared with <130/85 mm Hg found a more significant improvement in diastolic BP. Duration of intervention <8 weeks did not result in a significant reduction in systolic or diastolic BP. Furthermore, subgroup analysis of trials with daily dose of probiotics <1011 colony-forming units did not result in a significant metaanalysis effect. The authors conclude that consuming probiotics may improve BP by a modest degree, with a potentially greater effect when baseline BP is elevated, multiple species of probiotics are consumed, the duration of intervention is ≥8 weeks, or daily consumption dose is ≥1011 colony-forming units.

Hypertension. 2014. PMID: 25047574.

In this study, the authors carried out meta-analyses based on 343 peer-reviewed publications that indicate statistically significant and meaningful differences in composition between organic and non-organic crops/crop-based foods. The results showed that the concentrations of a range of antioxidants such as polyphenolics were found to be substantially higher in organic crops/crop-based foods, with those of phenolic acids, flavanones, stilbenes, flavones, flavonols and anthocyanins being an estimated 19 (95 % CI 5, 33) %, 69 (95 % CI 13, 125) %, 28 (95 % CI 12, 44) %, 26 (95 % CI 3, 48) %, 50 (95 % CI 28, 72) % and 51 (95 % CI 17, 86) % higher, respectively. The frequency of occurrence of pesticide residues was found to be four times higher in conventional crops, which also contained significantly higher concentrations of the toxic metal Cd. Significant differences were also detected for some other (e.g. minerals and vitamins) compounds. There is evidence that higher antioxidant concentrations and lower Cd concentrations are linked to specific agronomic practices prescribed in organic farming systems. The authors conclude that organic crops, on average, have higher concentrations of antioxidants, lower concentrations of Cd and a lower incidence of pesticide residues than the non-organic comparators across regions and production seasons. Br J Nutr. 2014. PMID: 24968103.

Antioxidant vitamin supplementation reduces arterial stiffness: systematic review This systematic review and meta-analysis investigated the effect of antioxidant vitamins on arterial stiffness and to determine whether the effects on arterial stiffness vary according to dose, duration of intervention, and health or nutritional status of the included participants.

The authors searched 3 databases (Medline, Embase, and Scopus) for articles that potentially met the following eligibility criteria: 1) randomized controlled trials comparing antioxidant vitamins (vitamins C, E, and A and β-carotene) to either placebo or no active control in 2) adult participants aged ≥18 y; 3) antioxidant vitamins administered alone or in combination, irrespective of dose, duration, and route of administration; and 4) changes in arterial stiffness or arterial compliance. Data synthesis showed that antioxidant vitamins reduced arterial stiffness significantly (SMD: -0.17; 95% CI: -0.26, -0.08; P < 0.001). This effect was significant in experimental (SMD: -1.02; 95% CI: -1.54, -0.49; P < 0.001) and primary prevention (SMD: -0.14; 95% CI: -0.24, -0.04; P < 0.01) studies, whereas a trend for reduced arterial stiffness was observed in studies including participants with diseases (SMD: -0.19; 95% CI: -0.40, 0.02; P = 0.08). The authors conclude that supplementation with antioxidant vitamins has a small, protective effect on arterial stiffness. The effect may be augmented in those with lower baseline plasma vitamins E and C concentrations. J Nutr. 2014. PMID: 25098780.

October 2014 | www.ihpmagazine.com

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research news Impact of oral vitamin C on histamine levels and seasickness In this study, the authors aimed to determine whether vitamin C suppresses nausea in 70 volunteers who spent 20 minutes in a life raft, exposed to one-meterhigh waves in an indoor pool. It was a double-blind placebo-controlled crossover study. Two grams of vitamin C or placebo was taken one hour before exposure. Blood samples were taken one hour before and after exposure to determine histamine, diamine oxidase, tryptase, and vitamin C levels. Symptom scores were noted on a visual analog scale. On the second day the test persons were asked which day they had felt better. The results showed that test persons had less severe symptoms after the intake of vitamin C (p< 0.01). Scores on the visual analog scale were in favor of vitamin C, but the difference was not significant.

Twenty-three of 63 persons wished to leave the raft earlier: 17 after the intake of placebo and 6 after the intake of vitamin C (p< 0.03). Women (p< 0.02) and men below 27 years of age (p< 0.02) had less pronounced symptoms after the intake of vitamin C. The authors conclude that some of the data show that vitamin C is effective in suppressing symptoms of seasickness, particularly in women and men younger than 27 years of age, and is devoid of side effects. Histamine levels were initially increased after the test persons had been exposed to waves. J Vestib Res. 2014. PMID: 25095772.

Soy dietary supplement and low dose hormone therapy on cardiovascular health: RCT In this study, the authors assessed the effects of a soy dietary supplement on the main biomarkers of cardiovascular health in postmenopausal women compared with the effects of low-dose hormone therapy (HT) and placebo. It was a double-blind, randomized and controlled intention-to-treat trial. Sixty healthy postmenopausal women, aged 40-60 years, 4.1 years mean time since menopause were recruited and randomly assigned to 3 groups: a soy dietary supplement group (isoflavone 90mg), a low-dose HT group (estradiol 1 mg plus noretisterone 0.5 mg) and a placebo group.

Lipid profile, glucose level, body mass index, blood pressure and abdominal/hip ratio were evaluated in all the participants at baseline and after 16 weeks. The results showed that after a 16-week intervention period, total cholesterol decreased 11.3% and LDL-cholesterol decreased 18.6% in the HT group, but both did not change in the soy dietary supplement and placebo groups. Values for triglycerides, HDL-cholesterol, glucose level, body mass index, blood pressure and abdominal/hip ratio did not change over time in any of the three groups. The authors conclude that the use of dietary soy supplement did not show any significant favorable effect on cardiovascular health biomarkers compared with HT. Rev Bras Ginecol Obstet. 2014. PMID: 25099464.

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www.ihpmagazine.com | October 2014

Vitamin D and erectile dysfunction In this study, the authors evaluated the status of serum Vitamin D in a group of patients with ED. Diagnosis and severity of ED was based on the IIEF-5 and its etiology was classified as arteriogenic (A-ED), borderline (BL-ED), and nonarteriogenic (NA-ED) with penile-echocolor-Doppler in basal condition and after intracaversous injection of prostaglandin E1. Serum vitamin D and intact PTH concentrations were measured. The results showed that fifty patients were classified as A-ED, 28 as ED-BL and 65 as NA-ED, for a total of 143 cases. Mean vitamin D level was 21.3 ng/mL; vitamin D deficiency (<20 ng/mL) was present in 45.9% and only 20.2% had optimal vitamin D levels. Patients with severe/complete-ED had vitamin D level significantly lower (P = 0.02) than those with mild-ED. Vitamin level was negatively correlated with PTH and the correlation was more marked in subjects with vitamin D deficiency. Vitamin D deficiency in A-ED was significantly lower (P = 0.01) than in NA-ED patients. The authors conclude that that a significant proportion of ED patients have a vitamin D deficiency and that this condition is more frequent in patients with the arteriogenic etiology.

Low levels of vitamin D might increase the ED risk by promoting endothelial dysfunction. J Sex Med. 2014. PMID: 25092061.

Pre Natal SAP

Science-based multivitamin for pregnant women Vitamin and mineral supplementation, while planning for parenthood and during pregnancy, helps ensure optimal nutrition for the health of the mother and unborn baby. Pre Natal SAP provides therapeutic doses of a variety of supplemental nutrients aimed at preventing and correcting vitamin and mineral deficiencies, and achieving benefits seen beyond typical dietary intake levels.

ACTIVE INGREDIENTS

Each non‑GMO vegetable capsule contains: Vitamin C (calcium ascorbate) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58.33 mg Vitamin D (cholecalciferol) [333.33 IU] . . . . . . . . . . . . . . . . . . . . . . . . . 8.33 mcg Vitamin E (d-alpha-tocopheryl acetate) [16.667 IU] . . . . . . . . . . . 11.15 mg AT Vitamin K (vitamin K1) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33.33 mcg Vitamin B1 (thiamine hydrochloride) . . . . . . . . . . . . . . . . . . . . . . . . . . . 33.33 mg Vitamin B2 (riboflavin-5’-phosphate sodium). . . . . . . . . . . . . . . . . . . 16.66 mg Niacinamide (vitamin B3) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16.66 mg Vitamin B6 (pyridoxal-5’-phosphate) . . . . . . . . . . . . . . . . . . . . . . . . . . . 16.66 mg l-Methylfolate (from calcium l-5-methyltetrahydrofolate) (folic acid) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333 mcg Vitamin B12 (methylcobalamin) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333 mcg Biotin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 mcg Vitamin B5 (calcium d-pantothenate) . . . . . . . . . . . . . . . . . . . . . . . . . . 33.33 mg Calcium (from calcium citrate). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58.33 mg Iron (from iron glycinate) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 mg Iodine (from potassium iodide) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 mcg Magnesium (from magnesium citrate) . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 mg Zinc (from zinc citrate). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.33 mg Selenium (from l-selenomethionine) . . . . . . . . . . . . . . . . . . . . . . . . . 16.66 mcg Copper (from copper citrate). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 666 mcg Manganese (from manganese citrate) . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.66 mg Chromium (from chromium polynicotinate) . . . . . . . . . . . . . . . . . . 33.33 mcg Molybdenum (from molybdenum citrate) . . . . . . . . . . . . . . . . . . . . 16.66 mcg Potassium (from potassium citrate) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 mg Boron (from boron citrate) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233.33 mcg Contains no: Preservatives, artificial flavour or colour, sugar, dairy, starch, wheat, gluten, yeast, soy, citrus, or eggs.

Pre Natal SAP contains 180 capsules per bottle.

DOSAGE

Adults: Take 3 capsules daily. If you are taking other medications, take this product a few hours before or after them. Take with food.

INDICATION

Pre Natal SAP provides nutritive support for women who are pregnant or who are planning to become pregnant.

Noninclusion of the nutrients beta‑carotene and vitamin A: high doses of vitamin A have been shown to cause birth defects when taken during pregnancy. Our formula provides health-care practitioners with the flexibility to supplement these micronutrients separately as needed.

INCREASED BIOAVAILABILITY

ɶ ɶ

Pre Natal SAP is not compressed with binders, for superior assimilation.

Pre Natal SAP is supplied in a vegetable capsule for easy digestion.

PURITY, CLEANLINESS, AND STABILITY

Third-party testing is performed on the finished product to ensure Pre Natal SAP is free of heavy metals, pesticides, 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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Pre Natal SAP PRODUCT MONOGRAPH

Micronutrient status in women of reproductive years is of extreme importance, especially around the time of conception. Micronutrient supplementation is recommended for all women around this time to cover the gap in maternal nutrition and to avoid nutrient deficiency leading to complications of pregnancy and adverse fetal outcomes. Micronutrient status can influence the health of the woman during her pregnancy, the health and development of the fetus, and even years of infancy.

Due to the rapid changes in the female body and the demands of the developing fetus, nutritional status is paramount as there are critical windows of development.

Nutritional deficiencies during this time can affect the development of the immune system, and have implications to cardiovascular, spinal, musculoskeletal, neurological, and metabolic function. It is always prudent to ensure adequate micronutrient status.

MINERALS

Iron is essential to blood oxygen-carrying capacity. Iron bisglycinate chelates have been shown to be superior in absorption and bioavailability to other forms of iron.[1, 2, 3] Specifically, iron bioavailability as a glycine chelate was reported to be 3.4 times greater than that of ferrous sulfate,[4] with reduced incidences of side effects including gastric irritation and constipation (33% less). Iron deficiency anemia imposes a risk of hemorrhage during delivery. It is also associated with the risk of preterm delivery. Iron bisglycinate may negate the necessity for its coadministration with vitamin C for absorption, due to substantially increased bioavailability.[5] Zinc is essential to human metabolism and catalyzes more than 100 enzymes, facilitates protein folding and regulates gene expression. Zinc deficiency may cause complications during pregnancy and delivery, as well as growth retardation, congenital abnormality, and retarded neurobehavioral and immunological development. Iodine deficiency has an effect on thyroid function and can influence rate of conception, and can lead to cretinism and possible preterm delivery.

Calcium and magnesium are critical for musculoskeletal development and influence nerve signaling. Magnesium is a cofactor for many enzymatic reactions. Magnesium can also help to decrease complications during pregnancy, such as inflammation and pain, by having analgesic action. Magnesium can also help to relax muscles and cramps.[6] Magnesium, vanadium and chromium play a role in blood glucose metabolism, transport and insulin sensitivity. These minerals can greatly decrease the risk of gestational diabetes.

ANTIOXIDANTS, BIOFLAVONOIDS, VITAMIN C AND VITAMIN E

Antioxidants, working in a complex synergistic system, play a major role in humans to quench free radicals and reactive oxygen species, the metabolic paradox of using oxygen as an energy source. The function of the antioxidant system is to prevent damage by free radicals to DNA, protein and lipid structure—the integral base of cell physiology. Antioxidants, a family to which vitamins C and E as well as the bioflavonoids belong, act as inhibitors at stages of initiation and promotion of tumor growth and proliferation and mitigate neoplastic processes.[7] During pregnancy, it is crucial to have a handle on oxidative stress as it can lead to complications in pregnancy. Oxidative stress can lead to impaired placental perfusion, immune maladaptation and inflammation.[8] Increased levels of oxidative stress markers and decreased levels of antioxidants are found in women who experience preeclampsia.[9] Vitamin C is also a cofactor in multiple enzymatic reactions, particularly to do with the immune system and blood vessel health.

Vitamin C prevents and reduces the duration and severity of the common cold, plays a role in the stress response, and increases the absorption of iron.

B VITAMINS AND FOLATE

B vitamins are required by the human body for metabolic processes, most notably involved in enzymatic processes required for energy production, maintain healthy skin and muscle tone, play a role in the development and maintenance of healthy immune and nervous system, promote cell growth and cell division and are required for healthy blood cell development.

Along with vitamin B12, folic acid plays a role in nucleic acid synthesis and carbon metabolism. Low maternal folate levels are correlated with smaller newborn weight, and contribute to congenital malformations such as neural tube defects (NTD).

Since the fortification of folate in foods, NTD has decreased by 50–70%.[10] More recent studies suggest B12 supplementation can further decrease the risk of NTD.[10] Recently, it has been suggested that folic acid-containing multivitamins may also be beneficial in preventing congenital anomalies other than NTD such as a decreased risk for orofacial clefts, limb deficiencies, and cardiovascular abnormalities.[11] Increased levels of both folate and B12 help to lower levels of homocysteine, which may contribute to NTD and early pregnancy loss.[12] Low levels of B12 and folate are also risk factors for the development of type 2 diabetes[13] and cardiovascular disease.

For more information visit: www.nfh.ca

IHP 2014-10,11 (Pre Natal SAP).indd 2

Supplementing B12 will also help avoid other complications during pregnancy, such as macrocytic anemia and neurological complications affecting sensory and motor function.[14] Folic acid and B12 deficiency can also lead to other pregnancy complications. Higher pregnancy rates are found with micronutrient supplementation in those with and without fertility issues. Previous studies suggest that folic acid status may be important in the ovarian response to FSH and helps to regulate the cycle and that low levels of folate were found to be strongly associated to ovulatory infertility.[15] In age- and energy-adjusted analyses, intakes of vitamins B1, B2, B6, B12, folic acid and niacin were inversely related to the risk of ovulatory infertility.[15] Women with sufficient vitamin B6 showed a higher conception rate and lower risk of early pregnancy loss compared to those with vitamin B6 deficiency.[12] Suboptimal vitamin B6 status and elevated plasma concentrations of homocysteine, a marker of poor folic acid and/or vitamin B12 status, also have been associated with increased risk of clinical spontaneous abortion.[12] In addition, numerous studies have documented associations between low vitamin B6 status and inflammatory responses, and inflammation has been linked to early pregnancy loss.[12] B vitamin deficiency coupled with hyperhomocysteinemia are associated with recurrent abortion. B6 has also been shown to decrease nausea and vomiting in pregnancy.

VITAMIN D

Vitamin D is important for the development of bones, and an inadequacy of it can contribute to the development of rickets, a disease once thought to be eradicated.

Rickets is once again on the rise as people lather on sunscreen and limit sun exposure due to the damage UV rays can cause. The downside of this is that without direct sunlight exposure, the body cannot synthesize its own vitamin D. Expecting moms need to ensure adequate intake for both themelves and the fetuses to optimize proper development and strength of fetal bones, and maintenance of their own. The role of vitamin D is to maintain serum levels of minerals such as calcium and phosphorus to support metabolic function, neuromuscular transmission, regulate bone metabolism and enhance immunity.

Studies show that at week 28, 100 mg/d of calcium is being deposited in the skeleton.

At week 35, calcium deposition increases to 350 mg/d.[16] Building adequate stores of vitamin D for the newborn is important to the maintenance of the structure.

Maintenance of vitamin D levels postnatally is also important, especially to those born premature, to avoid skeletal abnormalities. Vitamin D levels impacts fetal shape and limb length.[17] Fetal vitamin D insufficiency is linked to the increased risk of hypocalcemia, type 1 diabetes, asthma and schizophrenia.[18] New studies show that vitamin D status also helps to regulate placental development.

This indicates that vitamin D deficiency may contribute to complications in pregnancy such as miscarriage, preeclampsia, and preterm birth.[18, 19]

REFERENCES 1.

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Pizarro, F., et al. “Iron bis-glycine chelate competes for the nonheme-iron absorption pathway”. The American Journal of Clinical Nutrition Vol. 76, No. 3 (2002): 577–581.

Jeppsen, R.B. and J.F. Borzelleca. “Safety evaluation of ferrous bisglycinate chelate”. Food and Chemical Toxicology Vol. 37, No. 7 (1999): 723–731.

Hertrampf, E. and M. Olivares. “Iron amino acid chelates”. International Journal for Vitamin and Nutrition Research Vol. 74, No. 6 (2004): 435–443.

Pineda, O. and H.D. Ashmead. “Effectiveness of treatment of iron-deficiency anemia in infants and young children with ferrous bis-glycinate chelate”. Nutrition Vol. 17, No. 5 (2001): 381–384.

Pineda, O., et al. “Effectiveness of iron amino acid chelate on the treatment of iron deficiency anemia in adolescents”. Journal Of Applied Nutrition Vol. 46, Issue 5 (2001): 2–13.

Goyal, P., et al. “Role of magnesium sulphate for brachial plexus analgesia”. The Internet Journal of Anesthesiology Vol. 21, No. 1 (2009): 0–6.

Park, O.J. and Y.J. Surh. “Chemopreventive potential of epigallocatechin gallate and genistein: evidence from epidemiological and laboratory studies”. Toxicology Letters Vol. 150, No. 1 (2004): 43–56.

Kontic-Vucinic, O., M. Terzic, and N. Radunovic. “The role of antioxidant vitamins in hypertensive disorders of pregnancy.” Journal of Perinatal Medicine Vol. 36, No. 4 (2008): 282–290.

Sharma, J.B., et al. “Oxidative stress markers and antioxidant levels in normal pregnancy and preeclampsia”. International Journal of Gynaecology and Obstetrics Vol. 94, Issue 1 (2006): 23–27.

Molloy, A.M., et al. “Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic acid fortification”. Pediatrics Vol. 123, No. 3 (2009): 917–923.

Goh, Y.I., et al. “Prenatal multivitamin supplementation and rates of pediatric cancers: A meta-analysis”. Clinical Pharmacology and Therapeutics Vol. 81, No. 5 (2007): 685–691.

Ronnenberg, A.G., et al. “Preconception B-vitamin and homocysteine status, conception, and early pregnancy loss”. American Journal of Epidemiology Vol. 166, No. 3 (2007): 304–312.

Yajnik, C.S., et al. “Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study”. Diabetologia Vol. 5, No. 1 (2008): 29–38.

Green, R. “Is it time for vitamin B12 fortification? What are the questions?” The American Journal of Clinical Nutrition Vol. 89, No. 2 (2009): 712S–716S. Chavarro, J.E., et al. “Use of multivitamins, intake of B vitamins and risk of ovulatory infertility”. Fertility and Sterility Vol. 89, No. 3 (2008): 668–676.

Holick, M.F. “Resurrection of vitamin D deficiency and rickets”. The Journal of Clinical Investigation Vol. 116, No. 8 (2006): 2062– 2072.

McGrath, J.J., et al. ‘Seasonal fluctuations in birth weight and neonatal limb length; does prenatal vitamin D influence neonatal size and shape?”. Early Human Development Vol. 81, Issue 7 (2005): 609–618.

Bodnar, L.M., et al. “High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates”. The Journal of Nutrition Vol. 137, No. 2 (2007): 447–452.

Bodnar, L.M., et al. “Maternal vitamin D deficiency increases the risk of preeclampsia”. The Journal of Clinical Endocrinology & Metabolism Vol. 92, No. 9 (2007): 3517–3522.

© NFH Nutritional Fundamentals for Health 2014

2014-09-17 2:02:12 PM

research news Multi-ingredient dietary supplement effects on body composition and health: RCT

Effects of ear acupuncture therapy for obesity on the depression of obese women In this study, the authors evaluated the effectiveness of ear acupuncture for obesity on the depression of obese women.

Obesity is one of the leading health risks worldwide, and depression is among the leading causes of the burden of disease.

After baseline testing, 30 eligible patients with body mass index (BMI) >29.9 kg/ m2 were included. The Beck Depression Inventory for Primary Care (BDI-PC) was used to assess changes in depression.

BMI was also measured. Patients had six ear acupuncture sessions, every 15 days and were followed up for 3 months.

Twenty four patients completed the study.

The results showed that the mean±SD age of patients was 42.9±9.0 years. Their mean±SD BMI was 39.0±4.7 kg/m2 before acupuncture, decreasing to 37.2±4.3 kg/ m2 after acupuncture therapy (p<0.001).

The mean depression score was 4.4±2.3 before acupuncture, decreasing to 2.7±1.4 (p<0.001) after treatment. There was no significant correlation between BMI and depression score before acupuncture therapy (p=0.104). After acupuncture therapy, no significant correlation was found between the percentage reduction of BMI and percentage reduction of the depression score (p=0.119). The authors conclude that further research into the effects of ear acupuncture in the management of obesity and depression is justified. Acupunct Med. 2014. PMID: 25098839.

In this study, the authors investigated the effects of a multi-ingredient dietary supplement (MIDS) containing caffeine, conjugated linoleic acid (CLA), green tea, and branched-chain amino acids (BCAA) taken for 8 weeks on body composition, blood lipid profile, glucose, insulin, adiponectin, leptin, and highsensitivity C-reactive protein (hs-CRP) in overweight and obese men and women.

Participants were randomly assigned and stratified by body fat percentage to two groups: 1) a soybean oil placebo (PL) or 2) MIDS. Each group consumed two pills with breakfast and two pills with lunch.

Body composition and android fat, waist and hip circumferences, blood pressure and heart rate were measured at baseline and after 8 weeks of supplementation. The results showed that there were no significant changes for any of the variables of body composition. Feelings of hunger were significantly higher in MIDS versus PL with no changes observed in satiety or desire to eat. Heart rate and blood pressure were unaltered in MIDS after 8 weeks of supplementation. Furthermore, lipid profile, food intake, mood state variables, fasting blood glucose, and endocrine markers did not significantly change regardless of group. The authors conclude that MIDS intake does not appear to alter body composition or markers of cardiovascular health versus PL. Moreover, MIDS may actually increase feelings of hunger versus PL. J Int Soc Sports Nutr. 2014. PMID: 25093015.

Effects of Chinese herbs combined with IVF on infertility: RCT In this study, the authors assessed the effects of using Chinese herbs in assisted reproductive technology. Four hundred and thirty-three subjects aged less than 42 years with infertility due to Fallopian tube or male-related factors who were willing to undertake in vitro fertilization and embryo transplantation were randomly allocated to a Chinese herb intervention group (n = 216) or a conventional treatment control group (n = 217). All subjects received one of four routine ultra-ovulationpromoting therapies at the Reproductive Center in the Third Hospital Affiliated to Beijing University according to their physician's assessments. The subjects in the intervention group received various Chinese herbs depending on their conventional treatment. The results showed that the high-quality embryo rate of 51.9%, biochemical pregnancy rate of 51.0%, clinical pregnancy rate of 44.2% and endometrial thickness of (10.84 +/- 1.75) mm in the intervention group were all significantly higher than those in the control group [48.7%, 38.9%, 34.8%, and (10.52 +/- 1.50) mm, respectively; P < 0.05].

The normal fertility rate of 58.5% in the Chinese herb group was also significantly superior to the 54.7% achieved in the control group (P < 0.01). The authors conclude that Chinese herbs increase endometrial thickness, improve the quality of fertility and embryo, and promote embryonic nidation. J Tradit Chin Med. 2014. PMID: 24992752.

October 2014 | www.ihpmagazine.com

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research news RCT of withania somnifera extract for cognitive dysfunction in bipolar disorder In this study, the authors assessed the cognitive effects of a standardized extract of the medicinal herb Withania somnifera (WSE) in bipolar disorder. Sixty euthymic subjects with DSM-IV bipolar disorder were enrolled in an 8-week, double-blind, placebo-controlled, randomized study of WSE (500 mg/d) as a procognitive agent added adjunctively to the medications being used as maintenance treatment for bipolar disorder. Study enrollment and data analyses were completed between December 2008 and September 2012. Cognitive testing at baseline and 8 weeks assessed primary efficacy outcomes. Psychopathology and adverse events were monitored at scheduled visits. The results showed that compared to placebo, WSE provided significant benefits for 3 cognitive tasks: digit span backward (P = .035), Flanker neutral response time (P = .033), and the social cognition response rating of the Penn Emotional Acuity Test (P = .045). The size of the WSE treatment effect for digit span backward was in the medium range (Cohen d = 0.51; 95% CI, 0.250.77). None of the other cognitive tasks showed significant between-group differences.

Mood and anxiety scale scores remained stable, and adverse events were minor. The authors conclude that, WSE appears to improve auditory-verbal working memory (digit span backward), a measure of reaction time, and a measure of social cognition in bipolar disorder. J Clin Pyschiatry. 2013. PMID: 24330893.

Physical activity level and sleep duration and cardio-metabolic risk profile In this study, the authors examined independent and combined cross-sectional and longitudinal associations between movement behaviors and the metabolic syndrome (MetS) score in 8-11 year old Danish children. Physical activity, sedentary time and sleep duration (seven days and eight nights) were assessed by accelerometer and fat mass index (fat mass/ height2) was assessed using Dual-energy X-ray absorptiometry. The MetS-score was based on z-scores of waist circumference, mean arterial blood pressure, homeostatic model assessment of insulin resistance, triglycerides and high density lipoprotein cholesterol. All measurements were taken at three time points separated by 100 days. The results showed that physical activity was negatively associated with the MetS-score. In the longitudinal analysis, low physical activity and high sedentary time were associated with an increased MetS-score; however, after mutual adjustments for movement behaviors, physical activity and sleep duration, but not sedentary time, were associated with the MetS-score. Further adjusting for fat mass index while removing waist circumference from the MetS-score rendered the associations no longer statistically significant. Children in the most favorable tertiles of changes in moderate-to-vigorous physical activity, sleep duration and sedentary time during the 200-day follow-up period had an improved MetS-score relative to children in the opposite tertiles. The authors conclude that physical activity, sedentary time and sleep duration should all be targeted to improve cardio-metabolic risk markers in childhood. PLoS One. 2014. PMID: 25102157.

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www.ihpmagazine.com | October 2014

White mulberry supplementation as adjuvant treatment of obesity In this study, the authors evaluated the adjuvant slimming effect of the extract of white Japanese mulberry in the dietetic treatment of some patients who are obese or overweight. 46 overweight people were enrolled and divided into two subgroups: the subjects of both subgroups were given an identical balanced diet of 1300 kcal: subjects of the subgroup alpha received 2400 mg of white Japanese mulberry extract, the subgroup b subjects receive placebo. Each subgroup was followed-up every 30 days at 30, 60 and 90 days of treatment. Both in the periodic inspections and in the final inspection measurements of body weight and waist circumference in all the subjects and thigh circumference in women only were repeated. In the subgroup alpha, weight loss was about 9 kg in 3 months, equal to approximately 10 percent of the initial weight, significantly higher than subgroup beta (P<0.0001); moreover, the plasma insulin and glucose curves of the volunteers in this subgroup at the end of the trial were lower than those performed at the time of enrolment. Waist circumference and thigh circumference (in women) decreased in all participants, obviously more evidently in subjects who lost more kg. The authors conclude that the extract of white Japanese mulberry may represent a reliable adjuvant therapy in the dietetic treatment of some patients who are obese or overweight. J Biol Regul Homeost Agents. 2014. PMID: 24750800.

The PROBIOTIC most recommended by pharmacists in Canada* Helps to REDUCE the RISK of Clostridium difficile-Associated Diarrhea in hospitalized patients

Helps to REDUCE the RISK of Antibiotic-Associated Diarrhea

* Gao et al. 2010. Dose-response Efficacy of a Probiotic Formula in Reducing Clostridium difficile-associated Diarrhea. AM J Gastroenterology. 105(7); 1636-1641.

Pharmacy Practice+ & L’actualité pharmaceutique 2014 Survey on OTC Counselling & Recommendations

Bio-K+ 50 Billion CFU Probiotic Capsule ®

• NPN: 80015104 (Helps to reduce the risk of Antibiotic Associated Diarrhea) • NPN: 80038453 (Helps to reduce the risk of C. Difficile Associated Diarrhea in hospitalized patients)

Pharmacology

Hospital Protocol Administration

Potential Mechanisms of Action It was shown that L. acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2® 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 hours1. 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)2,3. The 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. Count4.

Bio-K+® is an effective solution to add to an existing hospital protocol to help reduce Clostridium (C.) difficile infections. This recommendation is based on clinical studies done with the 50 billion CFU probiotic capsule. Bio-K+® is effective when given in prophylaxis to adult patients (18+) under antibiotic treatment. Protocol administration: 2 capsules of Bio-K+® 50 Billion after the first dose of the prescribed antibiotic therapy, and continue daily usage of Bio-K+® for 5 additional days after completion of the antibiotic therapy. Bio-K+® should be administered within 2 hours after consuming the first antibiotic dose. The procedure is different for patients with a nasogastric tube. A nasogastric tube (NGT) or Levin tube is a flexible probe inserted via the nose or the mouth in order to reach the stomach. The tube can also reach the small intestine (nasoduodenal tube). This intervention requires a medical prescription and can have multiple purposes:

Health Claim5 • Helps to reduce the risk of Clostridium diffcile associated diarrhea (CDAD) in hospitalized patients.

• Helps to reduce the risk of Antibiotic Associated Diarrhea (AAD).

• 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.

• 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®, L. casei LBC80R® and L. rhamnosus CLR2® 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®, L. casei LBC80R® and L. rhamnosus CLR2®. Non medicinal ingredients: ascorbic acid, cellulose, ethylcellulose, hypromellose, magnesium stearate, medium chain triglycerides, silicone dioxide, sodium alginate and titanium dioxide. Packaging options are: • 15 capsules: one bottle contains 15 capsules • 100 capsules: one box includes 10 sheets of 10 blister packed capsules • 250 capsules: one bottle contains 250 capsules • 1,000 capsules: one shipper includes 10 boxes of 10 sheets of 10 blister packed capsules Refrigerate at 4°C for maximum activity.

• Ensure the emptying of the stomach, eliminate gas (air and gastric secretions).

• Before an intestinal surgery.

• Liquid administration.

• Allows stomach washing.

• Allows to feed the patient on a short time period (force-feeding administration).

• Analysis of gastric liquid.

Millette et al.1 demonstrated that the Bio-K+® enteric coated capsules confer an excellent gastrointestinal (GI) survival to the probiotic strains. Millette et al.4 demonstrated the GI survival of the same strains under a pH ≥ 2.5 (without an enteric coating). It is not recommended to open the capsules, to rehydrate the lyophilized bacteria in a liquid and to consume the obtained suspension. The lyophilized bacteria are more sensitive to the acidity. If there are no other options available (i.e. patients with NGT receiving intravenous antibiotics), follow these steps to optimize the effectiveness of the Bio-K+® formula and to assure the safety of the patients: 1. Do not open the Bio-K+® capsules in the patient’s room.

2. Open and add the powder of one or two Bio-K+® capsules to 30mL of physiologic sterile water.

3. Stir the mixture with the tip of a 50 CC syringe.

4. With the 50 CC syringe, take the bacterial mixture.

5. Disinfect the external side of the syringe before bringing it in a patient’s environment.

6. Inject the suspension in the NGT, 15 minutes after the administration of a meal if possible.

7. Rinse the force-feed tube with 30 mL of physiologic water.

industry news Healthy sodas not too hard for Canadians to swallow, as 41% are interested Many Canadians are constantly looking for ways to adopt a healthier diet and monitor what ingredients they are eating and drinking, as seen by the fact that more than half (52%) say that they like to check the ingredients on the packaging of carbonated soft drinks (CSDs). However, rather than give up their favorite fizzy beverage, it seems that a high share of Canadians are more interested in healthier adaptations of their favorite soft drinks.

Indeed, new Mintel research finds that four in 10 (41%) Canadian CSD users would be interested in CSDs that aid digestive health. Additionally, one third (36%) of these users would be interested in buying CSDs that contain botanical extracts and 46% agree that types with less sweet flavors would complement a meal better. This underlines the potential for brands to continue driving the profile of the ‘lighter’ segment of the market, which stands at $3 billion overall, compared to over $41 billion in the US. “There may be opportunities for CSDs to leverage functional benefits to boost usage in the category. Interestingly, this would hark back to when these products were first introduced and were marketed with claims that they could aid digestion.” says Warren de Lima, senior research analyst at Mintel.

“Functionality has been a boon to markets such as energy drinks, with brands delivering tangible benefits to users. While there remain some difficulties for brands to use approved claims, this represents an area worth further exploration.” When it comes to choosing a particular carbonated soft drink, health again plays a role. 29% of users state that low/no calorie content would make them choose one type of CSD over another and 14% would be attracted to a CSD with natural ingredients. This is of particular relevance, since the attribute which Canadian CSD drinkers are most likely to associate with them is that they are artificial (62%). Younger consumers are also surprisingly the most likely to agree that carbonated drinks which are less fizzy appeal to them, with agreement peaking among 18-24s at 35%, well ahead of the overall average (24%).

Canadians desperate for a national seniors care strategy as population ages Nearly all Baby Boom Canadians aged 45 years and over (95 per cent) identify the need for a panCanadian seniors care strategy, according to the Canadian Medical Association's (CMA) 2014 National Report Card on health issues. Not only are 81 per cent of these Canadians concerned with the quality of health care they can expect in their future, 78 per cent are worried about their ability to access quality home and long-term care in their retirement years, the Ipsos Reid poll found. "As the Canadian Baby Boom generation looks down the road to the future they see clearly that Canada desperately needs a seniors strategy and politicians should pay attention during the next federal election. This should be an issue one would ignore at their own political peril," CMA President Dr. Louis Hugo Francescutti said. The poll results highlight the urgency of this issue and that it remains a pertinent concern for all those interested in accessing efficient health care as they age-both for themselves and their loved ones, said Ipsos Mike Colledge, President Public Affairs at Ipsos Reid. Nine out of 10 respondents (91 per cent) agreed a national seniors care strategy would improve the overall health care system. Elderly patients could be cared for at home or in long-term care facilities, alleviating chronic hospital bed shortages that are pushing up wait times for everything from emergency treatment to hip transplants. Furthermore, this type of infrastructure planning would lend itself to a better use of health care dollars.

One day of care for a patient in a hospital remains high at $1, 000. By contrast, one day spent in a long-term care facility costs about $130 and home care $55. The CMA estimates at least $2.3 billion a year could be used in a more effective way in the health care system. While there is an obvious need to create more efficient and effective community care for seniors, six out of 10 respondents were not confident these existing facilities will be able to handle the needs of an aging population and eight in 10 were not confident that they will even have access to these services. The results also show that there appears to be more acute concern about health care in old age among those aged 45 to 54.

Health Canada Statement on Risks to Youth of Marijuana and Prescription Drug Use Health Canada regularly undertakes evidence-based communications to raise awareness about serious public health issues. From 2007 to 2012, for example, as part of the government's National Anti-Drug Strategy, the Department developed the DrugsNot4Me mass media campaign. The Department also engages with partners on smoking cessation campaigns like "Break It Off ". As standard practice, the Department seeks partnerships and invites health professionals to share their insights and experiences to ensure that they have captured the risks accurately. The intent of the campaigns is educational and the material is based on evidence and science. The proposed focus, messages and concepts for such campaigns are routinely informed by consultation sessions where health professional groups identify sound public health messaging. The prevalence and health risks of marijuana and prescription drug use and abuse make them compelling public health issues in Canada. Marijuana is the most widely used illegal drug among Canadian youth today. According to the 20122013 Canadian Youth Smoking Survey, one in five students reported using marijuana in the year preceding the survey. The average age of initiation being 14 years old.

Prescription drug abuse is also having a devastating impact on communities and people of all ages across the country. According to a 2013 report of the International Narcotics Control Board, Canada is now the second-largest per capita consumer of prescription opioids, behind only by the United States. In 2012, about 1 million youth, aged 15 to 24 years, reported having used a psychoactive pharmaceutical in the past 12 months. Health Canada will continue to work to find ways to raise awareness among parents and youth about the health risks of marijuana and prescription drug abuse.

October 2014 | www.ihpmagazine.com

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industry news Professional Advice Within Reach for Millions of Canadians Living with Arthritis The Arthritis Society has partnered with Guardian, I.D.A., PROXIM and the Medicine Shoppe pharmacies to launch an exclusive pain management program to support Canadians living with arthritis directly in their communities. Designed

by The Arthritis Society, the unique pain management program will be rolled out in participating pharmacies in Autumn 2014 under the diem™ therapeutic brand.

Pharmacists that have been trained and certified under the program will be able to provide a wide-range of tailored health services to those living with arthritis, including osteoarthritis and rheumatoid arthritis. Under the diem™ brand, pharmacists will offer bundles of professional services and companion products, thus allowing patients to access complete and integrated support to optimize their drug therapies and minimize side-effects. "Customized patient care is at the heart of the programs and services we offer," explains Jim Snowdon, Guardian pharmacist. "Thanks to this unique diem™ pain management offering, Canadians living with arthritis will be able to obtain holistic therapeutic support from their neighborhood Guardian, I.D.A., PROXIM and the Medicine Shoppe pharmacist." "This new initiative will make a true difference in the lives of Canadians living with arthritis by giving them increased access to professional, qualified care down the street and across the counter," saidJanet Yale, President and CEO of The Arthritis Society. "By increasing the convenience and ease with which Canadians can receive specialized counsel, this program will help those with arthritis get the help they need to live with less pain and greater independence." Pharmacy in Canada is undergoing a major transformation, as provincial governments expand the scope of professional services that pharmacists can offer and shift patient care into community settings," noted Dale Weil, Interim Senior Vice President of Retail Banner Management Services at McKesson Canada, which operates the four retail pharmacy banners. "Through our network of 1,350 stores from coast to coast to coast, Guardian, I.D.A., PROXIM and the Medicine Shoppe pharmacists are responding to the growing needs of Canadians living with chronic disease and complex medical conditions by providing customized patient care."

CMA Recognizes Dr. Eric Wasylenko for Excellence in the Field of Medical Ethics The Canadian Medical Association (CMA) announced today that Dr. Eric Wasylenko of Calgary will receive the 2014 Dr. William Marsden Award in Medical Ethics. This award recognizes CMA members who have demonstrated exemplary leadership, commitment and dedication to the cause of advancing and promoting excellence in the field of medical ethics in Canada. "Dr. Wasylenko's commitment to furthering the cause of medical ethics in Canada makes him highly deserving of the award," said Dr. Louis Hugo Francescutti, CMA President. "He has made a remarkable contribution to the growing awareness of end-of-life care issues." "I feel honoured to have been nominated and to receive the CMA's Dr. William Marsden Award in Medical Ethics," Dr. Wasylenko said. "Every day I witness the amazing efforts of my clinical and administrative colleagues working with patients and their families to provide the best care possible. Increasingly, clinical and organizational decision-making incorporates challenging ethical issues, without obvious ways forward. I am appreciative of the opportunities to do my small part in helping people to successfully navigate these often murky waters. "Both end-of-life care and medical ethics foster deep exploration of personhood. I feel privileged to be allowed into the depth of a person's hopes, fears, relationships, uncertainty, joys, conflicts, sense of mortality – in short, their humanity.

Practising in the areas of medical ethics and end-of-life care challenges me to tap into the lessons that patients and colleagues teach me about the art of medicine." Dr. Wasylenko is a pioneering palliative care physician in residential hospice and homebased palliative care. He led the creation of one of Canada's first rural, communityowned, free-standing, residential hospice homes.

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Possible cardiovascular problems associated with testosterone products Health Canada is advising patients and healthcare professionals of new safety information regarding testosterone hormone replacement products and a risk of serious and possibly lifethreatening cardiovascular (heart and blood vessel) problems. Testosterone hormone replacement products are used in men who are experiencing medical conditions because their body cannot make enough testosterone.

In Canada, there are 12 testosterone replacement products, including brand-name products: Androderm, Andriol, Delatestryl, Androgel, Axiroin, Depo-Testosterone, Testim, and their equivalent generics. Health Canada has recently completed a safety review on testosterone replacement products. This review found a growing body of evidence (from published scientific literature and case reports received by Health Canada and foreign regulators) for serious and possible life-threatening heart and blood vessel problems such as heart attack, stroke, blood clot in the lungs or legs; and increased or irregular heart rate with the use of testosterone replacement products. Health Canada is working with manufacturers to update the Canadian product labels regarding this risk. The Department continues to collaborate with foreign regulators including the United States Food and Drug Administration and the European Medicines Agency regarding this safety concern. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified. Health Canada would like to remind the public of the following important information from the Canadian Product Monographs regarding the use of testosterone products: They should not be used in men for non-specific symptoms if laboratory tests have not been done to confirm a low testosterone level and other possible causes for the symptoms have not been excluded. They should not be used in children under the age of 18 as the safety and effectiveness has not been established in these patients.

They should not be used by women.

www.ihpmagazine.com | October 2014

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2014-10-17 10:52 AM

Plasma curcumin (mcg/ml)

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Superior Bioavailability of MicroActive® Resveratrol Compared to 98% Resveratrol Control

ResCu-SR™ Synergistic combination of highly bioavailable MicroActive® sustained-release, 98% pure resveratrol and curcuminoids Exclusive to Pure Encapsulations

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 Patented MicroActive delivery system improves solubility, reduces particle size, improves absorption and provides sustained-release of polyphenols ®

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Figure 1. In a human study, subjects received a single dose of either MicroActive® Resveratrol or an equivalent dose of 500 mg pure (98%) resveratrol (control). Peak plasma concentrations, AUC and duration in plasma were superior to control, and sustained release was evident over the 24-hour period.

 Supports cardioprotection and neurological health  Modulates gene expression to support longevity and antioxidant defenses

Superior Bioavailability of MicroActive® Curcumin Compared to a Standard Curcumin Control

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60 50

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Figure 2. In subjects who received MicroActive® Curcumin as a single dose equivalent to 250 mg curcumin, Tmax for MicroActive® Curcumin was 2 hours followed by sustained release forresveratrol over 9 98% pure 0.8 hours. Cmax for MicroActive® Curcumin was 30-fold greater than for ® 0.7curcumin (250 mg dose of total curcuminoids). AUC for Resveratrol MicroActive MicroActive 0.6Curcumin was 8.6-fold greater than curcumin.

Plasma resveratrol (mcg/ml)

0.9

®

0.5 0.4 0.3 0.2 0.1 0

0

2

4

6 Time (hours)

8

10

Your Trusted Source for research-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.

The ResCu-SR™ trademark is used by Pure Encapsulations under license.

Plasma curcumin (mcg/ml)

70

ResCu-SR™

MicroActive® Curcumin

50 40 30 20 10 0 -10

What Is It?

Standard 95% curcumin

60

0

2

4 6 Time (hours)

8

10

Superior bioavailability of MicroActive® Resveratrol

ResCu-SR™ offers a unique combination of highly bioavailable, sustained-release resveratrol and curcumin to support longevity, and overall health.

Plasma resveratrol (mcg/ml)

0.9

Uses For ResCu-SR

™

Overall Health: Resveratrol and curcumin have each been the subject of over 4,000 studies and are among the most extensively researched polyphenols.

An emerging body of clinical evidence also reveals a progressive convergence of clinical indications for these compounds. Both curcumin and resveratrol are widely recognized approaches to longevity, cardioprotection and neurological health. Recent mechanistic studies have characterized functional synergy and cooperativity in antioxidant activity, signal transduction and gene expression.

What Is The Source?

Resveratrol is synthetic. Curcuminoids are derived from Curcuma longa (turmeric) extract (root).

Are There Any Potential Drug Interactions?

Resveratrol and curcuminoids may be contraindicated with blood thinning medications. Consult your physician for more information.

Are There Any Potential Side Effects Or Precautions?

If pregnant or lactating, consult your physician before taking this product. It is recommended to use resveratrol cautiously in patients with hormonal disorders and those using estrogen therapy, as resveratrol may act as either an estrogen agonist or estrogen antagonist. Turmeric can cause nausea or diarrhea in some individuals. It is not recommended for individuals with biliary obstruction. Consult your physician for more information.

0.6 0.5 0.4 0.3 0.2 0

0

10 Time (hours)

Figure 1. In a human pilot study, peak plasma resveratrol concentrations were 2.5-fold greater following a single dose of MicroActive® Resveratrol compared to standard 98% pure resveratrol. After 9 hours, plasma resveratrol levels were 6-fold greater with MicroActive® Resveratrol.

Superior bioavailability of MicroActive® Curcumin* 70 Plasma curcumin (mcg/ml)

ResCu-SR™ was developed using a proprietary MicroActive® delivery technology that renders a soluble, sustained-release resveratrol (MicroActive® resveratrol) and a soluble micronized curcumin (MicroActive® curcumin). Superior solubility and absorption performance have been confirmed in dissolution studies and pharmacokinetic trials of both compounds. The MicroActive® technology is a patented delivery system that improves solubility, reduces particle size, improves absorption and provides sustained-release of polyphenols. In a human pilot study, peak plasma resveratrol and area under the curve (AUC) values were 250% greater with MicroActive® Resveratrol compared to an equivalent dose of 98% pure resveratrol. Superior plasma concentrations remained after a 9-hour period (Figure 1). In a separate human trial, peak plasma curcumin levels were 4 to 60-fold greater with MicroActive® Curcumin compared to an equivalent dose of a standard 95% curcumin preparation (Figure 2). Superior plasma concentrations remained after a 9-hour period.

® MicroActive Resveratrol

0.7

0.1

Standard 95% curcumin

60

®

MicroActive Curcumin

50 40 30 20 10 0 -10

0

2

4 6 Time (hours)

8

10

Figure 2. In a human pilot study, a single dose of MicroActive® Curcumin increased plasma curcumin to levels exceeding those achieved with a standard 95% curcumin by 4 to 60-fold over a 9-hour period.

0.9 Recommendations 0.8 Plasma resveratrol (mcg/ml)

Innovative sustained-release delivery technology

98% pure resveratrol

0.8

98% pure resveratrol

Resveratrol Pure Encapsulations recommendsMicroActive 1–2 capsules daily, with meals.

0.7 ®

0.6

™ ResCu-SR 0.5

0.4 each vegetarian capsule contains 0.3

v 00

trans-resveratrol (from MicroActive® resveratrol sustained-release complex) ........100 mg 0.2 curcuminoids (from MicroActive® curcumin sustained-release complex) ...................50 mg 0.1 other ingredients: cellulose, silica, potato starch, carnauba wax, polysorbate 80, isopropyl 0 sodium alginate, vegetarian capsule (cellulose, water) myristate, 0

10

1–2 capsules daily, with meals.

Time (hours) The ResCu-SR™ trademark is used by Pure Encapsulation under license.

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.

industry news Attend the IN-CAM Research Symposium The IN-CAM Research Symposium is the premier research symposium in complementary and integrative medicine in Canada: http://www.incamresearch.ca/ content/welcome-2014-symposium Dates: November 6-8, 2014 Place: Calgary Marriott Downtown, 110 9th Ave SE, Calgary, AB T2G 5A6 Register early and save over 50% on registration fees Early bird deadline: October 6th, 2014 The Symposium has become established as the primary research meeting in Canada in this area. It brings together a diverse group of individuals from across disciplines, representing a range of research expertise and research interests.

The Symposium creates an environment that enables discussion and facilitates the generation of new ideas and collaborations across Canada. The 2014 Symposium is particularly special as it marks IN-CAM’s 10th anniversary. IN-CAM was created and has been thriving as a Canadian research network in the field of CAM and integrative medicine and health since 2004. During the Symposium, we will highlight the various stories and successes of IN-CAM members.

Naturopathic Medicine Week Supports Victoria’s Family Free Clinic Proceeds from the film screening of GMO OMG during Naturopathic Medicine Week (NMW) were provided to the Family Naturopathic Clinic (FNC) in July.

The FNC provides naturopathic health care free-of-charge to young parented, low income families in Victoria. NMW, an annual event promoting health, wellness and preventive medicine, occurs across Canada each May. This year, the new documentary on GMO foods was shown to specifically support the FNC. Dr. Penny Seth Smith, Victoria’s NMW Coordinator, noted that the success of the film screenings, in Victoria, Vancouver and Kelowna, were an opportunity to share naturopathic expertise as well as raise awareness of preventive medicine in local communities. “I am delighted to have been a part of organizing this event, and

want to thank the hundreds of people who participated. We look forward to repeating this success next year.” Dr. Janine Fraser, BCNA Vice-President, added that “The FNC offers graduating doctors an opportunity for internships, improves access to NDs amongst low income families, and helps improve health care services for patients across the island. Only with more financial support can it continue to grow and serve even greater numbers.” The FNC, a project begun in 2007, provides medical services free of charge through donations and fund-raising. The clinic is not government funded. As one patient noted, “Overall, this project has been invaluable and precious in my life. I listen, I learn, I heal. I am a better mother because of this project and my son has an improved quality of life.”

Safe use of topical antiseptics for preoperative and preinjection skin preparation Health Canada is reminding healthcare professionals, caregivers and consumers of the safe use of topical antiseptics used to clean the skin before an operation (preoperative) or before an injection (preinjection). These products can be considered safe and effective; however, if proper care is not taken when using them, they can become contaminated and cause serious, subsequent infections. This class of topical antiseptics is used to remove microorganisms such as bacteria or fungi on the patient’s skin prior to injections or surgery. In Canada, these products are available as single-use or multi-use products, and contain ingredients such as ethyl alcohol, isopropyl alcohol, povidone-iodine, and chlorhexidine gluconate. Topical antiseptics that are sterile will be labelled as such, with the word sterile appearing on the label. Health Canada is aware of the recent U.S. Food and Drug Administration (FDA) Drug Safety Communication on over-the-counter topical antiseptic products. The U.S. FDA has confirmed 88 cases of infections linked to the contamination of antiseptics, including four deaths. These cases included serious, life-threatening complications such as infection of the lining of the abdominal organs (peritonitis), infection in joints (septic arthritis) , wound infections, indwelling catheters needing replacement, injection site infection, and bacteria in blood. To date, Health Canada has not received any confirmed adverse reaction reports of infection linked to the use of topical antiseptics contaminated by improper use, handling, or storage. To minimize the risk of infection, Health Canada reminds Canadians to: Read all product labels and follow all labelled directions; Discard single use products after a single application; Do not dilute products after opening them; Do not use products that have been sitting exposed in open containers; Do not use products after their expiration dates.

Cannabis Science to Establish Its First Medical Cannabis Facilities in Canada Cannabis Science, Inc., a U.S. company specializing in cannabis formulation-based drug development and related consulting, is in the final stages of launching a new joint venture company for the purpose of acquiring, financing, building, owning and operating medical cannabis facilities, including dispensaries and growing operations, throughout Canada. The Company believes that this joint venture has the potential to expand the Company’s operations outside of the United States and to allow the Company’s entry and expansion into Canada’s marketplace. “Acquiring cannabis facilities in Canada represents a compelling business opportunity developed through our focus on collaborative innovation and takes one of our international initiatives to the next level,” said Chad S. Johnson, Director, COO and General Counsel of the Company. “We are excited to be working jointly with our partners, which allows us to leverage our respective global research knowledge and resources to facilitate the Canadian operations. The Company also intends to use these facilities for research and development purposes in addition to the selling of the cannabis products under relevant laws and regulations. More to come.”

While the Company is optimistic about the potential for commercialization of cannabis products, it recognizes that, as with the acquisition and development cannabis facilities, the process can be lengthy and without assurances.

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calendar OCTOBER October 18 Biotherapeutic Drainage and UNDA Compounds Organized by: Seroyal Seattle, WA For more information, visit http://www.seroyal.com

October 30 Individualized Nutrition: Mechanisms of Epigenetics Organized by: Seroyal Online Teleconference For more information, visit http://www.seroyal.com

November 19 Women’s Health, Part Two: Effective Herbal Therapies in Obstetrics Organized by: AARM Online Teleconference For more information, visit http://www.restorativemedicine.org

NOVEMBER

November 20 CSOM Talk By Dr. Eric Marsden, ND Organized by: CSMO For more information, visit http://www.csom.ca

October 19 The Advantage of Phytotherapy: A simple, efficient therapy Organized by: Seroyal Seattle, WAFor more information, visit http://www.seroyal.com

November 5 Stress Management and Adrenal Exhaustion Organized by: Seroyal Online Teleconference For more information, visit http://www.seroyal.com

October 20-22 Dollars and Sense: Leadership in Delivery of Cost-effective Healthcare Organized by: CMA Toronto, ON For more information, visit http://cma.ca/pmi

November 6-8 Nurse Practitioners’ Conference Organized by: NPAO Hamilton, ON For more information, visit http://www.npao.org

October 23-25 Management Dynamics: Getting the Job Done Organized by: CMA Toronto, ON For more information, visit http://cma.ca/pmi October 25-26 Improve Clinical Outcomes and Elevate Your Practice Organized by: Seroyal Calgary, AB For more information, visit http://www.seroyal.com October 26-27 Clinical Homeopathy Training Program Organized by: CEDH Toronto, ON For more information, visit http://www.cedhusa.org October 26-27 Science and Connection: Integrative Health and Medicine Conference Organized by: Scripps’ and ABIHM San Diego, CA For more information, visit http://www.scripps.org/events 24

www.ihpmagazine.com | October 2014

November 7-8 IN-CAM Research Symposium Organized by: IN-CAM Calgary, AB For more information, visit: http://www.incamresearch.ca November 8-9 Individualized Nutrition for Women’s Health: Beyond Bio-identical Hormones Organized by: Seroyal Toronto, ON For more information, visit http://www.seroyal.com November 9-10 Nutrition for Docs: Part II Organized by: CSOM Toronto, ON For more information, visit http://www.csom.ca November 13 How to Build Your Practice Using Biotherapeutic Drainage Organized by: Seroyal Online Teleconference For more information, visit http://www.seroyal.com

November 21-23 OAND Convention Organized by: OAND Niagara Falls For more information, visit http://www.oand.ca November 23-24 Clinical Homeopathy Training Program Organized by: CEDH Toronto, ON For more information, visit http://www.cedhusa.org November 23-24 Developing and Leading System Improvement Organized by: CMA Vancouver, BC For more information, visit http://cma.ca/pmi November 23-25 Physician as a Coach Organized by: CMA Vancouver, BC For more information, visit http://cma.ca/pmi November 25-26 Quality Measurement for Leadership and Learning Organized by: CMA Vancouver, BC For more information, visit http://cma.ca/pmi

product profiles

Legend

r s y s s e g h n h h al ine ine thy alt sur nce ete iatr tric tric itio alt alt tic llin a c c se ceu edi edi eop He res Ca iab ych edia eria utr e He s He n r N n ’ D Ps P P u a G l ra n M l M om n o s t d t u u a C Nu H or m me sc loo sia nic / et Sp Im Wo Va B Di nal . A ota io B ad r rt it T Nu

Cysto Renew - Bladder Support Formula Cysto Renew™, developed by Dr. Geo Espinosa, is a unique combination of ingredients including Lemon Balm and Rhodiola designed to help calm the bladder and support healthy functioning of the urinary tract system. Each ingredient contributes to the health of the bladder glycosaminoglycan layer, nitric oxide production, healthy stress response, and normal mast cell production that helps promote a healthy functioning bladder and normal urine frequency.

VSL#3® VSL#3®is a high potency blend of 8 different probiotics. It contains the highest concentration of probiotic bacteria (450 billion CFU per sachet) available in Canada.

Curcumin Active from AOR Curcumin Active contains Optimized Curcumin, the most bioavailable curcumin on the market with bioavailability increases of over 100-fold.

Curcumin Active provides curcumin’s plethora of benefits including relieving inflammation and joint pain in a low dose of 1 to 2 capsules a day. Optimized Curcumin is exclusively available in Canada from AOR.

NEW Easy-toSwallow Fish Oil from Progressive Each OmegEssential® JEWELS mini softgel has 50% more EPA than most regular strength softgels and it’s only half the size!

October 2014 | www.ihpmagazine.com

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NPN 80012473

Probiotic drops Lactobacillus reuteri DSM 17938 (L. reuteri Protectis ) TM

Digestive Health and Colic Relief

What are BioGaia Probiotic Drops used for?

Provide live microorganisms to benefit health and/or to confer a health benefit.

Infants: BioGaia helps reduce episodes (duration) of crying in infants suffering from colic.

What is the Active Ingredient in BioGaia Probiotic Drops?

5 drops contain a minimum of 100 million live active Lactobacillus reuteri DSM 17938 (L. reuteri Protectis) What is a probiotic?

The word “probiotic” means “for life” as opposed to antibiotics which mean “against life”. Probiotics are clinically proven, health fortifying, natural active bacterial cultures. Or as the World Health Organization (WHO) chose to describe it: “Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host.”

Not all probiotics are alike. Experts believe that the benefits of probiotics are strain-specific and recommend that all probiotics should be independently tested and evaluated in clinical trials as BioGaia Probiotic Drops have been.

What are BioGaia Probiotic Drops?

Lactobacillus reuteri Protectis is a patented probiotic bacteria that is in BioGaia Probiotic Drops. Because L. reuteri occurs in the human body it is uniquely adapted to live in humans. With its exceptional and documented health benefits in several areas, L. reuteri is considered a truly superior probiotic.

BioGaia Probiotic Drops are a probiotic that helps promote a healthy, balanced digestive system when taken daily. BioGaia Probiotic Drops have demonstrated beneficial effects on common digestive upsets such as diarrhea, constipation, gas and bloating.

Are BioGaia Probiotic Drops safe?

Safety studies with L. reuteri have been conducted in healthy newborns, small children, adults and immuno-deficient adults over the past decade. In all of these studies, L. reuteri has been proven to be free from side effects, even when given in doses greatly exceeding the levels normally contained in L. reuteri products. Over 3.5 billion daily doses of L. reuteri have been consumed all over the world since 1996, without any reported side effects.

How long does it take to feel the effects of taking Biogaia Probiotic Drops?

Normally you should notice the effects within a few days. While people who are healthy may not experience any differences, those taking L. reuteri because of a digestive system disturbance may notice an improvement in symptoms after 3-4 days. In some cases it may take longer if the person is, for example, taking a medication affecting the digestive system.

Dosage: Adults, Children and Infants: 5 drops once a day or use as directed by your health care practitioner.

For use beyond 21 days, consult your health care practitioner. If antibiotics are being taken, take at least 2-3 hours before or after taking antibiotics.

Directions: Shake well before using. Warm BioGaia Probiotic Drops slightly by rolling the bottle back and forth in your hands for 1 minute. To get the daily dosage, turn the bottle upside down and the drops will form slowly. The drops may be given on a spoon or added to milk, water or any other suitable drink or food. Do not add to hot food or drink as this may damage the live cultures. The drops do not change the taste of food or drink. Return BioGaia Probiotic Drops to the refrigerator after use. Opened bottle should be used within 3 months.

Non-medicinal Ingredients: Sunflower oil, medium chain triglyceride oil and silicon dioxide. BioGaia Probiotic Drops do not contain preservative or alcohol.

Cautions and Warnings: Discontinue use and consult a health care practitioner if symptoms of digestive upset (e.g. diarrhea), occur, worsen, or persist beyond 3 days.

Contraindications: Do not use if you are experiencing nausea, fever, 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).

200 Yorkland Blvd., Toronto, Ontario M2J 5C1 1-800-263-4057 ® BioGaia is a registered trade mark of BioGaia AB www.biogaia.com

3-340-11-4/5

3028-005

Storage: Keep refrigerated (2-8°C). Do not allow the bottle dropper to come in contact with any liquid, including saliva.

Keep the container closed. Opened bottle should be used within 3 months.

product profiles

Legend

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HMF Antibiotic Care HMF Antibiotic Care is a clinicallyproven probiotic that supplements the normal intestinal microbiota following antibiotic therapy. Provides 100 billion CFU of probiotic bacteria derived from proprietary human-sourced strains.

Pure Tranquility Liquid Pure Tranquility Liquid offers calming support combining inhibitory neurotransmitters GABA and glycine, along with L-theanine to support relaxation and stress reduction. Delivered in a convenient pleasant tasting liquid allowing for variability in dosing, Pure Tranquility Liquid enhances alpha wave production in the brain thereby promoting relaxation and relief of moderate occasional stress.

Hericium Erinaceus SAP (commonly called “Lion’s mane”): Science-based hot-water mushroom extract for optimal health and immune support: Hericium erinaceus (HE) has been called “nature’s nutrient for the neurons” because of its ability to stimulate production of nerve growth factor (NGF).

NGF plays an important role in both the central and peripheral nervous systems, and low levels have been associated with early stages of disorders such as dementia and Alzheimer’s disease. It has also demonstrated a beneficial effect on gastric mucosa damage seen with ulcerations. Hericium erinaceus has a positive impact on immune health and can support a healthy immune response.

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proteins+Natural Chocolate Peanut Butter Introducing a NEW flavour: proteins+Natural Chocolate Peanut Butter • Great tasting!

• Provides 28g of high quality alpha+TM whey protein isolate per serving • Blends easily with no clumping • Builds lean muscle* • Supplies a balance of all amino acids which helps build and repair body tissues • Builds antibodies

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Legend

r s y s s e g h n h h al ine ine thy alt sur nce ete iatr tric tric itio alt alt tic llin a c c se ceu edi edi eop He res Ca iab ych edia eria utr e He s He n r N n ’ D Ps P P u a G l ra n M l M om n o s t d t u u a C Nu H or m me sc loo sia nic / et Sp Im Wo Va B Di nal . A ota io B ad r rt it T Nu

product profiles

Carlson Prenatal Nutrition is extremely important during pregnancy, and Carlson Prenatal Multiple with DHA is formulated with a healthy child in mind. DHA promotes healthy nervous, immune, and cardiovascular systems as well as healthy vision and skin. Just two easy-toswallow soft gels a day provides the comprehensive nutrients mother and child need.

Curcummatrix Curcummatrix™ offers a patented technology specifically designed to increase the bioavailability.

Curcummatrix™ offers a solubility in duodenal conditions 7.5 times greater than the same amount of native curcumin.

Reishi SAP: Science-based hot-water mushroom extract for immune and stress support: this mushroom has been used as an herbal medicine to help increase energy and resistance to stress. The reishi mushroom has also been used as a liver tonic, as well as to support immune function. Reishi has properties that help support a healthy inflammatory response, and possesses antioxidant properties.

St Francis Herb Farm Introduces Encapsulated Herbal Extracts St Francis is launching a new line of encapsulated high potency dried herbal extracts. Encapsulated for convenience and concentrated effectiveness they provide all the benefits of liquid tinctures eliminating the need for large liquid or even capsules doses. The capsules feature a typical 5:1 concentration, meaning that every mg of encapsulated herb is 5 times more potent than the same amount in the raw herb form. Products include; Ashwagandha, Astragalus, Dandelion, Ginger, Hawthorn, Lemon Balm, Milk Thistle, Olive Leaf, Passion Flower, Rhodiola, Valerian, Echinace and Fenugreek/Blessed Thistle. Now available in bottle sizes of 60 Vegicaps representing a convenient one month supply.

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product profiles

Legend

r s y s s e g h n h h al ine ine thy alt sur nce ete iatr tric tric itio alt alt tic llin a c c se ceu edi edi eop He res Ca iab ych edia eria utr e He s He n r N n ’ D Ps P P u a G l ra n M l M om n o s t d t u u a C Nu H or m me sc loo sia nic / et Sp Im Wo Va B Di nal . A ota io B ad r rt it T Nu

Introducing NEW Vegan greens+ O natural vanilla flavour Now everyone can enjoy greens+ - the original and only RESEARCHPROVEN green food supplement.

We have specially formulated Vegan greens+ O for consumers who have allergies and sensitivities to certain foods and environmental chemicals.

PASCOFLAIR® - Be Stress Free and Sleep Well!

Mag-Matrix Liquid Mag-Matrix Liquid™ is a unique blend of highly absorbable magnesium sources- magnesium glycinate, malate and citrate.

Sweetened with xylitol and a subtle but pleasing natural lemon flavour.

PASCOFLAIR® is a unique preparation containing 425mg of Passionflower extract which works within 30 minutes to calm the brain and improve sleep onset due to stress. Studies also 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. Visit: www. pascoe.ca for more information.

Muco Coccinum Muco Coccinum is a homeopathic nosode preparation intended for the relief of cold and flu symptoms. Muco Coccinum includes a combination of bacterial and viral fractional lysates.

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PROGRESSIVE NUTRITIONAL THERAPIES OMEGESSENTIAL® JEWELS Progressive OmegEssential® JEWELS is a high potency blend of cold water, wild caught, purified fish oil along with a family of strategic support nutrients.

Fish Oils for the Maintenance of Good Health As a source of omega-3 fatty acids, namely EPA and DHA, fish oils aid in the maintenance of good health, help support cognitive health/brain function and cardiovascular health (NHPD Monograph: Fish Oil).

Fontani, et al (2005) conducted a study to evaluate the effect of omega-3 supplementation on cognitive performance in 33 normal healthy men and women (aged 22 – 51 years) during a 35-day period. Tests involving different types of attention were used, along with the Profile of Mood States (POMS). Results showed a mood profile with increased vigour and reduced anger, anxiety and depression states after omega-3.

Furthermore, findings indicated that omega-3 supplementation is associated with an improvement of attentional and physiological functions, particularly those involved in complex cortical processing.

Higher consumption of fish and omega-3 fatty acids has been associated with a lower risk of coronary heart disease (CHD). Hu, et al (2002) examined the association between fish and omega-3 fatty acid consumption and risk of CHD in women. Dietary consumption and follow-up data from 84,688 female nurses (aged 34 to 59 years) free from cardiovascular disease and cancer were compared from validated questionnaires. The outcomes indicated that women who consumed more fish and fish oil (omega-3 fatty acids) significantly reduced their risk of heart disease (particularly CHD deaths) by 30%, compared to women who rarely ate fish.

Similarly, a prospective, nested case-control analysis was performed among apparently healthy men, who had no evidence of prior heart disease by Albert, et al (2002) to address the hypothesis that long-chain omega-3 fatty acids found in fish are associated with a reduced risk of sudden death from cardiac causes. The fatty-acid composition of whole blood in 184 men was compared with the previously collected blood of 94 men, in whom sudden death occurred as the first manifestation of cardiovascular disease. The study reported that men who consumed long-chain omega-3 fatty acids had a significantly reduced risk of sudden death.

Dosage Indication: Fish Oil Supplement. Helps support cardiovascular health, brain function and healthy mood balance.

Adults (≥ 19 years) Dosage Take 2 softgels with breakfast and 2 softgels with dinner for a total of 4 softgels per day.

Interactions Omega-3 fatty acids may increase the risk of bleeding when taken with anticoagulants, aspirin, ginkgo biloba or ginseng (Mason, 2001).

Therefore, medical supervision is required.

Based on human studies, fish oils may lower blood pressure when taken in certain doses and have additive effects in patients treated with anti-hypertensives (Prisco, et al, 1998). Use with caution.

Quality Assurance Parameter Microbial Total Count Yeast & Mold Escherichia coli Salmonella spp Staphylococcus aureus Heavy Metal Arsenic Cadmium Lead Total Mercury

References Test

Specifications

USP USP USP USP USP

Less than 1,000 cfu/g Less than 100 cfu/g Negative Negative Negative

USEPA USEPA USEPA USEPA

Less than 0.25 ppm Less than 0.25 ppm Less than 0.25 ppm Less than 0.25 ppm

Albert C, et al (2002). Blood Levels of Long-Chain n-3 Fatty Acids and the Risk of Sudden Death. The New England Journal of Medicine, Vol. 346 No. 15: 1113-1118, April 11.

Fontani G, et al (2005). Cognitive and physiological effects of Omega-3 polyunsaturated fatty acid supplementation in healthy subjects. European Journal of Clinical Investigation, 35: 691-699.

Hu F, et al (2002). Fish and Omega-3 Fatty Acid Intake and Risk of Coronary Heart Disease in Women. The Journal of the American Medical Association, Vol. 287 No. 14, April 10.

Jellin JM, et al (2006). Pharmacist’s Letter/Prescriber’s Letter th Natural Medicines Comprehensive Database.8 ed. Stockton, CA: Therapeutic Research Faculty.

Mason P. Dietary Supplements. 2nd ed. London: Pharmaceutical Press; 2001.

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

Prisco D, et al (1998). Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients. Thromb Res. 1:105-12.

cover story

Dr Howard Libstug and Associates Holistic dentistry since before the term existed

By Philip Rouchotas Photography by Eric Forget

October 2014 | www.ihpmagazine.com

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cover story

T

his issue, our cover story takes us into the profession of dentistry. Dr. Howard Libstug DDS, is an established doctor of dentistry practicing in Vaughan for over 20 years. The Dr. Libstug and Associates clinic is a full service dental clinic, as well as offering spa services. Dr. Libstugâ&#x20AC;&#x2122;s goal is to deliver top-quality, patient-focused dental care as well as thorough patient education. In addition to practicing holistic dentistry including the safe removal of amalgams, Dr. Libstug incorporates use of select natural health products in treating his patients. In practice since 1989, Dr. Libstug has been practicing holistic dentistry since before the field existed.

Dr. Libstug is a graduate of the University of Toronto, completing an honours undergraduate degree in neurology in 1985, consistently finishing on the Deanâ&#x20AC;&#x2122;s List, as well as the University of Western Ontario where he graduated from dentistry in 1989. During his academic career, Dr. Libstug published several research papers as well. Upon graduation, Dr. Libstug continued his studies on exchange in Germany at the University of Hamburg, as well as in an internship at the Department of Oral and Maxillofacial Surgery in Jerusalem. Dr.

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Libstug has also been recognized as the youngest President that the York Region Dental Society has had to date. After graduation from dentistry, Dr. Libstug began practicing as an associate, quickly building his practice, both buying out his partner and outgrowing the original space.

In 2002, Dr. Libstug built his current clinic, a beautiful location with the feel of a heritage home. Although he desired to obtain an original heritage home, due to excess obstacles and red tape, he decided to build a new structure. The building was designed to imitate a beautiful old home, down to the use of antique lighting fixtures, interlocking walkways, and exterior gardens. Impressively, the 4000 square foot building was also constructed using green materials including natural wood and ceramic. The clinic has won several awards for its aesthetic charm and curb appeal.

Interested in the health sciences since high school, and active as a swim instructor and ski instructor, Dr. Libstug has always gravitated towards a holistic approach. He was drawn to dentistry in part due to its relatively independent practice environment.

Dr. Libstug has always embodied a holistic style of practice. Since

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1992, three years after graduating, Dr. Libstug has refused to use mercury amalgams. This was long before the ill health effects of mercury became widely known. When asked about this decision, Dr. Libstug explains that in the history of dentistry, there is over 200 years wherein use of silver (with mercury amalgams) or gold (mercury free) filling were utilized. As concerns around mercury arose, several countries had banned the use of amalgams, and even early on in his career, this was enough for Dr. Libstug to question the current practice of using mercury: “there were enough concerns to make me think we should look elsewhere” for alternatives to mercury. Instead, Dr. Libstug uses porcelainceramic as well as a tooth-colored filling material which is a composite resin, and which is “biocompatible.” These fillings are free of metals. When asked about the relative durability of these fillings, Dr. Libstug explains that while nothing can be expected to last forever, if done properly, composite can last as long as amalgams. Silver amalgams have a life span of five to 25 years, with a median of 15 years. Another contentious area within dentistry is use of x-rays; Dr. Libstug explains that in his practice, he seeks to use “as little radiation as possible.”

Dr. Libstug and Associates 2963 Major Mackenzie Dr. Maple, Ontario, L6A 3N9 Email : appointments@drhoward.ca Phone : (905) 832 8304 Spa : (905) 832 1513 Toll Free : (866) DrHoward

October 2014 | www.ihpmagazine.com

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The clinic places great emphasis on patient comfort, convenience, and top quality care. The clinic boasts comfortable dental treatment rooms with televisions for each patient, flexible scheduling including on Saturdays, and a child-friendly “Kids only” zone.

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Dr. Libstug’s interest in cosmetic and aesthetic techniques also led him to a more holistic practice. He explains that his goal in cosmetic dentistry is to “make things look more like nature,” mimicking nature and using as few chemicals as possible.

He offers safe amalgam removal techniques, although he does not necessarily “push” for people to remove such fillings.

When prescribing antibiotics, a routine prophylactic strategy in dental practice, he also prescribes probiotics. When conducting dental surgery, Dr. Libstug often recommends use of Arnica to reduce pain and swelling, and enhance tissue healing. Dr. Libstug also discusses appropriate use of natural health products with patients in his office. When encountering patients with diabetes or hypertension, he may recommend use of supplements such as coenzyme Q10, and is quick to enter a discussion on the benefits of diet and lifestyle strategies. Other natural oral care products offered at the clinic include organic lip balm made specially for the clinic, herb-based mouth rinse, gluten free oral care products, as well as toothpaste containing green tea extract, an important antioxidant and emerging antimicrobial agent. Dr. Libstug routinely shares information on basic supplements, organic food, and healthy dietary habits with his patients. As dentists have recently been granted an expansion of their prescription rights, the clinic has also become one of the first offering botox injection therapy to treat conditions such as migraine and temperomandibular joint dysfunction (TMJ).

cover story

Clinic Personnel

Dr. Howard Libstug, DDS Dr. Amirali Naghdi DDS Dr. Ian Raskin DDS Dr. Pawel Zajac DDS Dr. David A. Brown, Certified Orthodontist Andrea Basch, Registered Dental Hygienist Costanza Iaconetti, Registered Dental Hygienist Deryck Garlow, Registered Dental Hygienist Ester Rojas, Registered Dental Hygienist Lucia Barandica, Registered Dental Hygienist Mary Mignardi, Registered Dental Hygienist Anna George CDA II, Dental Assistant Level II Falguni Patel CDA II, Dental Assistant Level II Marta Melara, Hygienist Manager Teresa Capista, Assistant Manager Angie Paris BA., SPA General Supervisor & Marketing Director Christine, Licensed Medical Aesthetician Samantha Mera, Laser Technician & Clinic Director Angie Paris BA, General Practice Manager Joanne Joseph, Co-Owner & Management

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In addition to Dr. Libstug, the clinic team includes several associate dentists, an orthodontist, dental hygienists, as well as aestheticians. Associates include Dr. Amirali Naghdi DDS, Dr. Ian Raskin DDS, and Dr. Pawel Zajac DDS. Dr. David A. Brown is a certified orthodontist with over 20 years’ experience servicing both Vaughan and Newmarket. The clinic also includes a large staff of dental hygienists, spa personnel, managers and administrative support staff.

Dental services include family dentistry, orthodontics, dental hygiene, cosmetic dentistry, implants, preventative care, Zoom! whitening, and emergency dentistry. Among specific procedures, the following are offered: bonding, dental bridges, crowns, asleep dentistry (using conscious sedation), dental hygienist cleaning, endodontic treatment (root canal), full dentures, partial dentures, implants, inlays and onlays, oral cancer screening, orthodontics, veneers, and Zoom! Whitening.

The clinic places great emphasis on patient comfort, convenience, and top quality care. The clinic boasts comfortable dental treatment rooms with televisions for each patient, flexible scheduling including on Saturdays, and a child-friendly “Kids only” zone. The clinic staff focuses on patient education to help patients best understand and meet their oral health needs.

To this end, there is wonderful selection of patient education videos available for viewing on the clinic website: http://www. dentistinmaple.com/educational-videos.php Recently, Dr. Libstug has added spa services to the range of the clinic’s offerings. These include Botox for hyperhidrosis or excessive sweating, anti-aging facials, cosmetic botox injections, deep peel exfoliation, eyelash extensions, intense pulse light therapy, laser hair removal, microdermabrasion, and fillers Revanesse & Juvederm injections. Together, through this unique integration of dental and spa, the clinic offers a full array of dental care and cosmetic services.

IHP is grateful to the Dr Libstug and team of associates for allowing us to showcase their facility. It was inspiring to meet with an individual who evolved his practice holistically long before the concept of holistic dentistry became common terminology. Sticking to what he believed to be important, valuable, and safe, Dr Libstug evolved a style of dentistry that delivers world- class outcomes, while incorporating impressive tools from the world of integrative therapeutics. ■ 38

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These other components may include cholesterol, omega-6 fatty acids, saturated fatty acids, oxidation products and contaminants. Highly concentrated fish oil, like QÜELL, provide at least 75% active ingredients, leaving less room for nonessential compounds.

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clinic profile

Naturopathic Foundations Health Treating Clinic the cause

By Chris Habib, ND â&#x20AC;˘ Photography by Robyn Russell

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I

n this issue, we are pleased to be featuring the Naturopathic Foundations Health Clinic. In 2002, Dr. Iva Lloyd, ND decided to open one of the largest naturopathic clinics, at that time, in Markham Ontario. She credits part of her decision to being settled in her life and wanting to commit to a single clinic and single clinic location for her career. From the beginning, her focus has been on providing a full-service naturopathic clinic, including laboratory services, infrared sauna, weekly seminars, walk-in acute care and all naturopathic modalities including IV Therapy. The reason behind the name of the clinic was to acknowledge the importance of assisting patients in building a strong foundation for health.

The clinic boasts an impressive 2700 square feet with 8 treatment rooms. They are open 6 days a week and service approximately 100 patient visits per week. Initially, the clinic's vision was to provide integrative health care with a number of different practitioner types. Dr. Lloyd's vision has changed over the years and now the clinic operates as a fully naturopathic clinic, with 5 full-time naturopathic doctors. One of the reasons for the change was that as an integrative clinic it was challenging to build strong relationships with outside clinics as you are often offering similar services. Since moving to a solely naturopathic model, she has been able to provide a much clearer message: "We do one thing. We do Naturopathic medicine. We do it really well.â&#x20AC;?

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clinic profile

33 The Bridle Trail, Unit 3 Markham, ON, L3R 4E7 Phone: 905-940-2727 Email: info@naturopathicfoundations.ca Website: www.naturopathicfoundations.ca Blog: blog.naturopathicfoundations.ca In terms of practitioner focus at the clinic, Dr. Lloyd has a special interest in the mental-emotional aspect of health and healing, energy medicine and patients requiring detailed naturopathic assessments; Dr. Ramberan focuses on IBD, integrative cancer care and performs all the IV therapies in the clinic; Dr. May excels at seeing the somatic metaphors in patients and also focuses on musculoskeletal concerns, pelvic floor health and pediatrics; Dr. Cooper focuses on skin, detoxification and allergies; and Dr. Moscar has a focus on chronic disease and men’s health. As a result of these varying areas of expertise, the clinic sees a huge variety of patients, including a lot of seniors, men, teenagers, kids and perimenopausal women. The patients have a huge diversity of religion and languages. Naturopathic Foundations truly represents a diverse family-oriented clinic.

Every practitioner at the clinic practices with a similar model and philosophy of health and disease. They embrace patient-centered care and thorough assessments. They focus on addressing not only the functional aspect of a person, but the psychological and the structural. All practitioners provide some form of manual or energetic therapies, and utilize all naturopathic modalities. The team engages in weekly staff meetings where they discuss patient cases, new product offerings and current research. The naturopathic doctors in the clinic are known for their ability to truly identify the causes of disease.

Their assessment process starts with a 25 page questionnaire and includes a thorough intake that addresses not only health history and current symptoms, but the impact of the mental-emotional and structural aspects on one’s health.

The clinic offers an extensive range of laboratory testing including testing for heavy metals, environmental chemicals and food intolerance, and general labs to assess for and monitor acute and chronic diseases. They work with patients to ensure that the essential lab tests are done to properly guide treatment plans and to ensure that underlying pathologies are diagnosed early. They educate patients about the need to strive for optimal values, not just to address abnormal values. Dr. Lloyd actually worked with Gamma-Dynacare Laboratories to create a specific “Naturopathic Profile Assessment” test panel that looks at 35 separate parameters. Approximately 25% of the clinic's patients have all their labs done exclusively through the clinic. The clinic also creates detailed spreadsheets of lab results for their patients to track health parameters over time.

The clinic offers weekly seminars, most of them at no charge. The practitioners also do community talks and speak at professional conferences. Education of the public has always been a focus for the clinic. Through monthly newsletters, blogs and access to over 50 different clinic handouts, they are able to provide ongoing information on health-related topics.

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clinic profile

Every practitioner at the clinic practices with a similar model and philosophy of health and disease. They embrace patient-centered care and thorough assessments.

The strong reputation of the clinic within the community over the years has resulted in a good deal of referrals from medical doctors and other medical professionals. Continuing to foster and grow these relationships is a goal of the clinic.

The two biggest challenges that Dr. Lloyd experiences is “headline healthcare” and the belief that disease is random.

Dr. Lloyd explains: "Mass media has trained everyone to think that health problems can be fixed easily, so a lot of people are looking for a quick fix.” So many aspects of health, such as food, environmental chemicals, exercise etc., are conveyed as headlines that only portray a very small part of the story. As a response to the “headline healthcare” issue, Dr. Lloyd created a website of naturopathic information called www.ndhealthfacts. org. The website contains over 2000 pages and provides a detailed review of conditions from a naturopathic perspective as well as monographs on a number of natural health products and foods. Dr. Lloyd explains that when people believe that disease is random it often decreases their focus on self-care and their desire to be more proactive with their health. Recognizing that health is logical and spending the time to identify the causes of disease can save a lot of time and money in the long run.

The clinic focuses on educating people about self-care and how to create an ongoing foundation for health. They are known for their thorough assessments and their focus on treating the whole person. A large part of the clinic’s success is due to the strong relationships that they build with patients and with other professionals in the community. We thank Dr. Lloyd and her team for generously sharing their model of care with us. ■

Dr. Iva Lloyd, BScH, BCPP, ND Dr. Urszula May, MHSc, ND Dr. Kimberley Ramberan, BSc, ND Dr. Jacqueline Cooper, BSc, ND Dr. Anthony Moscar, BSc (Hons), ND Madeleine Lloyd, Office Manager Beth Riches, Reception

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TM

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

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PRODUCT mOnOgRaPh

PRODUCT MONOGRAPH OIL OF OREGANO

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

Human studies

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

Animal and In vitro studies

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

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

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

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

Toxicology

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

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

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

References

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

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

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

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

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

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

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

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

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

2006;69(2):369-75.

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

The Journal Of

1

p54

The Health Benefits of Nature Green spaces play a vital role in patient health

By Elizabeth Stavros, ND and Jenny Yukht, ND

2

p59

Maintaining your memory Natural products that support early cognitive decline and dementia

By Ronald G Reichert, ND

3

p65

Nutritional, Nutraceutical, and Herbal Supplements in the Treatment of Inflammatory Bowel Disease

A review

By Sukriti Bhardwaj, Ivana Camposilvan, Christine Chung, Everett Claridge, Matthew Lee, Calum Scott, Jordan Robertson

CE

p74

Metformin

Can a diabetes drug fight cancer?

By Maria Shapoval, ND and Heidi Fritz, MA, ND

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editor’s letter

Overdue for your dental check- up?

The Canadian Health Food Association held its annual convention in Toronto a couple of weeks ago... I recall attending years ago, when you may have seen three or four ND’s in attendance the entire weekend... Over the years ND’s have made the convention a frequent stop, and it is refreshing to see! I talked with no fewer than a 100 ND’s during the event. The convention provides an excellent opportunity to see what the public is being exposed to by industry, and I feel makes us better suited to discuss popular happenings with our patients.

IHP is excited to present our first cover story focused on the profession of dentistry... Dr Howard Libstug, DDS, has walked a path of holistic health his entire life, and decades ago began incorporating holistic principles and practices into his dental practice long before the concept of holistic dentistry was being discussed, let alone practiced. The issue’s clinic profile is focused on a friend and mentor, Dr Iva Lloyd, and the Naturopathic Foundations clinic in Markham, Ontario. Dr Lloyd has spent years as a fierce advocate of ND advancement throughout Ontario and Canada, while maintaining a clinic that delivers exceptional patient care.

The issue’s features include an excellent review of literature demonstrating direct health benefit from spending time in green spaces, a review of integrative strategies for dementia management, and another contribution by Dr Robertson and her army of McMaster students reviewing supplementation strategies in IBD. The issue’s CE article expands on Dr Schor’s article of offlabel prescriptions in cancer care with a focused discussion of metformin in integrative oncology.

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

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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 | Scott Jordan (416) 203-7900 ext. 6106 Production Manager | Erin Booth (416) 203-7900 ext. 6110 Junior Designer | Tamara Kelly Contributors Philip Rouchotas, MSc, ND Christopher Habib, ND Heidi Fritz, MA, ND Maria Shapoval, ND Elizabeth Stavros, ND Jenny Yukht, ND Ronald G Reichert, ND Jordan Robertson, ND Sukriti Bhardwaj Ivana Camposilvan Christine Chung Everett Claridge Matthew Lee Calum Scott President | Olivier Felicio (416) 203-7900 ext. 6107 Controller & Operations | Melanie Seth 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 Erin Poredos | Tel: (416) 203-7900 ext 6128 Email: erin@gorgmgo.com Circulation Rive Gauche Media 1235 Bay St., suite 400 Toronto, Ontario, M5R 3K4 Email: circulation@ihpmagazine.com

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

Published by IHP Magazine

Canada Post Canadian Publication Mail Agreement Number 4067800 The publisher does not assume any responsibility for the contents of any advertisement and any and all representations or warranties made in such advertising are those of the advertiser and not of the publisher. The publisher is not liable to any advertiser for any misprints in advertising not the fault of the publisher and in such an event the limit of the publisherâ&#x20AC;&#x2122;s liability shall not exceed the amount of the publisherâ&#x20AC;&#x2122;s charge for such advertising. No portion of this publication may be reproduced, in all or part, without the express written permission of the publisher. ihp magazine is pleased to review unsolicited submissions for editorial consideration under the following conditions: all material submitted for editorial consideration (photographs, illustrations, written text in electronic or hard copy format) may be used by ihr Media Inc. and their affiliates for editorial purposes in any media (whether printed, electronic, internet, disc, etc.) without the consent of, or the payment of compensation to, the party providing such material. Please direct submissions to the Editor, ihp magazine.

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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

Aoife Earls, MSc, ND Trafalgar Ridge Chiropractic and Acupuncture 2387 Trafalgar Road, Unit 7A Oakville, Ontario L6H 6K7 aearlsnd@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 M9L1W9 ndluhar@hotmail.com

Ashley Weber, HBSc, ND Upper Beach Health and Wellness 1937 Gerrard St E. Toronto, Ontario ashleywebernd@gmail.com Berchman Wong, ND Adjust Your Health 5809 Macleod Tr SW, Suite 218 Calgary, Alberta T2H 0J9 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 Christopher Knee, ND, MSc The Dempster Clinic â&#x20AC;&#x201C; Center for Integrated Medicine 97 Scollard Street Toronto, Ontario knee.christopher@gmail.com Claire Girgis, ND Zawada Health 201 City Centre Drive, Suite 404 Mississauga, Ontario L5B 2G6 claire@zawadahealth.com

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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 Elena Rossi, MSc, ND Mahaya Health Services 105-2 College Street Toronto, Ontario M5G 1K3 info@mahayahealth.com 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 12 Irwin Ave, Suite 200 Toronto, Ontario jiselle@healthhubclinic.com John David Millar, BSc, ND Jacksoncreek Natural Health Centre 187 Sherbrooke St. Peterborough, Ontario naturo@jacksoncreek.ca 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

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peer review Judith Ancheta, ND FertilityCare Toronto 688 Coxwell Avenue, Suite 100 Toronto, ON M4C 3B7 judy@drjudynd.com

Mandana Edalati, BA, ND Wellness Naturopathic Centre Suite 213-1940 Lonsdale Ave North Vancouver, British Columbia V7M 2K2 dredalati@gmail.com

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

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

Kendra Smith, ND 115 Hurontario Street, Suite 200 Collingwood, ON drkendra.nd@gmail.com

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

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

Nicole Egenberger, BSc, ND Remede Naturopathics 214 Sullivan Street Suite 3B New York, New York 10012 nicole.egenberger@remedenaturopathics.com Nicole Sandilands, ND Durham Natural Health Centre 1550 Kingston Rd, Suite 318 Pickering, Ontario L1V 1C3 info@dnhc.ca Rajesh Ragbir, ND Scarborough Naturopathic Clinic 1585 Markham Road, Suite 211 Scarborough, Ontario M1B 2W1 ragbir.nd@gmail.com Raza Shah, BSc, ND St. Jacobs Naturopathic 1-9 Parkside Drive St. Jacobs, Ontario N0B 2NO stjacobs.nd@gmail.com Rochelle Wilcox, BA, ND Living Well Integrative Health Centre 2176 Windsor Street Halifax, Nova Scotia B3K 5B6 drwilcox@balancehealthcentre.ca

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 Shawna Clark, ND Forces of Nature Naturopathic Clinic 2447 1/2 Yonge St Toronto, Ontario M4P 2E7 info@shawnaclarknd.com Stephanie Swinkles, DDS Elmsdale Dental Clinic 4-269 Highway 214 Elmsdale, Nova Scotia N2S 1K1 steph_moroze@hotmail.com Susan Coulter, BSc, ND Roots of Health 2-497 Laurier Ave Milton, Ontario L9T 3K8 scoulter@rootsofhealth.ca Sylvi Martin, BScN, ND Fusion Chiropractic and Integrative Health 735 Danforth Avenue Toronto, Ontario M4J 1L2 sylvi.martin@gmail.com Tanya Lee, BSc, ND The Health Centre of Milton 400 Main St East Suite 210 Milton, Ontario L9T 1P7 tanyalee.nd@gmail.com Terry Vanderheyden, ND Bayside Naturopathic Medicine 118 Bay Street Barryâ&#x20AC;&#x2122;s Bay, Ontario KOJ 1B0 doctrv@gmail.com Theresa Jahn, BSc, ND Living Well Integrative Health Centre 2176 Windsor Street Halifax, Nova Scotia B3K 5B6 info@theresajahn.com

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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 has served on the Board of Directors of the Canadian Association of Naturopathic Doctors for six years, three of those years as the Chairman of the Board. In that position he chaired both the Canadian Naturopathic Coordinating Council and the Canadian Naturopathic Foundation. He received the Dr. Verna Hunt Award for his service to the profession. He held Adjunct Faculty of Medicine positions with the University of Northern British Columbia in the Norther Medical Program for nine years, working with new students in the Medical Program, introducing them to medical sociology and Naturopathic Medicine. Dr. Boxtart has been in private practice with his wife Dr. Cher Boomhower since 2002, co-founders of the Northern Centre for Integrative Medicine. NCIM is a multidisciplinary practice in northern BC. His practice focus is chronic musculoskeletal pain and integrative oncology. Dr. Boxtart is currently the Team Leader for British Columbia for the Pure Norths’ Energy Foundation. Pure North is a unique health care organization, providing primary prevention medical services to vulnerable populations throughout western Canada.

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.

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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 was the first Canadian Naturopathic Physician to qualify with a fellowship from the American Board of Naturopathic Oncology in 2007. 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 integrated health care facilities in Canada. Dr. Parmar was a consulting naturopathic physician at the Lions Gate Hospital cancer clinic from 2008 to 2012. He has established collaborative relationships with many oncologists and other practitioners, ensuring patients are provided a truly integrative and evidence-guided treatment. Dr. Parmar is also active in writing and lecturing in the fields of clinical hyperthermia, the tumour microenvironment, and integrative oncology. He continues to serve as a board member for the Oncology Association of Naturopathic Physicians, a position he has held since 2008. He is licensed by the College of Naturopathic Physicians of B.C.

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.

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The Health Benefits of Nature

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Green spaces play a vital role in patient health

By Elizabeth Stavros, ND and Jenny Yukht, ND

Elizabeth Stavros, ND HealthCare365 1867 Yonge St Suite 905, Toronto ON Elizabeth.Stavros@healthcare365.org Jenny Yukht, ND Momentum Chiropractic & Sports Therapy 15165 Yonge St Unit 2, Aurora JennyYukhtND@gmail.com

Introduction In today’s world, where people are more distanced from nature than ever before, researchers have begun turning their attention toward investigating nature’s role in human health.

Alan Logan ND and Eva Selhub MD released their co-authored book “Your Brain on Nature” in 2012 where they assemble the scientific evidence around the psychological, social, and physical health benefits of nature and advise physicians to recommend “Vitamin G” aka green space, to patients. It was author and researcher Richard Louv who pioneered popular interest in this topic in 2005 and coined the name “Nature Deficit Disorder” to highlight the growing gap between people and nature. He postulates a theory called “The Nature Principle” and states that reconnection with the natural world is fundamental to human health and well-being (Louv 2005). His theories and ideas are now supported by a growing body of scientific evidence showing that the healing power of nature transcends herbs and supplements to include physical activity or contemplation in the presence of nature.

Japanese researchers have long been looking at the health effects of time in nature, or what they call “forest bathing” or “forest medicine” (Logan 2013). The studies are various, and though not all have robust sample sizes, their collective results nonetheless support the conclusion that there is only benefit to be derived from spending time in nature.

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Spending time in a natural setting can also aid in the recovery of cognitive functions after they have been taxed.

Effects of Green Exercise Exercise is part of almost all ND’s treatment plans. A systematic review published in 2011 concluded that there are benefits to mental and physical well-being resulting from exercising in nature. The research team analysed data from 11 randomised and non-randomised control trials comprising 833 adults.

Eligible trials were those that compared the effects of outdoor exercise with indoor exercise and that reported physical or mental well-being outcomes. The review found improvement in mental well-being: increased energy and feelings of revitalisation, and decreased tension, anger and depression compared with exercising indoors. Participants also reported greater enjoyment and satisfaction with outdoor activities (Coon 2011).

A 2010 meta-analysis by Barton et al showed dose responses for duration of exposure to nature and intensity of exercise on the psychological parameters of mood and self-esteem. The greatest changes came from as little as five minutes of activity, thus suggesting that psychological measures are immediately increased by green exercise. The benefits were lower for 10-60 minutes of exposure, but rise again for whole-day duration.

For intensity the greatest benefits are derived from either light activity or vigorous activity, but interestingly drop for moderate activity (Barton 2010).

Nature reduces cortisol levels Chronically elevated cortisol levels are frequently seen in our patient base in clinical practice. Stressful jobs, lack of sleep, and inadequate exercise levels are often the culprits. Cortisol is an important biological mediator of illness, and plays an important role in the progression of most diseases. A study by Vogelzangs et al (2010) showed that high levels of cortisol measured in urine were associated with a dramatic increase in death from cardiovascular disease. Study participants with the highest levels were five times more likely to die from a heart attack or stroke than those with the lowest level. Since heart disease is the most common cause of death in North America, measures to decrease risk are essential.

A small but compelling Japanese cross-over study in 2007 (Park) demonstrated the differences in salivary cortisol and prefrontal lobe activity between participants who spent a day in a forested area and those that spend the day in an urban area.

When exposed to the natural setting, the participants not only had up to 50% lower levels of salivary cortisol compared to urban exposure, but also had significantly lower activation of the prefrontal cortex, which corresponds to their increased subjective 56

ratings of comfort and calmness. Essentially, participants were feeling a lot less stressed and on “high-alert” when they were spending time in a natural setting.

It seems that it is not absolutely necessary to go as far as finding a forest to achieve a state of reduced stress. A study by Roe et al (2013) found that exposure to natural ‘green spaces’ within urban neighbourhoods resulted in healthier diurnal cortisol responses in middle-aged men and women from deprived urban environments, as well as reducing their perception of stress. This suggests that the dose of nature need not be massive to achieve the desired stress-reducing effect.

Nature improves mental health Very recently, a large cross-sectional population study out of Wisconsin (Beyer 2014) looked at the prevalence of various mental health symptoms seen with depression and anxiety and correlated the symptoms to the amount of neighbourhood green space. The researchers controlled for a multitude of confounding factors, including demographic data, socio-economic status, and even the level of health insurance. They concluded that people living in greener neighbourhoods (as measured by percentage of tree canopy) had better mental health outcomes. The potential for self-selection is the largest limitation of this particular study, however the body of evidence on green spaces in general lends this study’s conclusions legitimacy.

Living in a greener area seems to improve mental health outcomes in the long-run as well. A longitudinal study done by Alcock et al (2014) showed that the mental health scores of people who moved to greener areas improve, while the scores of those who moved to less green areas deteriorate. Amongst those who moved to less green areas, the mean inverse score on the General Health Questionnaire fell from 10.15 to 9.99 right after the move, though it rose back up, suggesting an accommodation to the new environment. No such accommodation was necessary amongst those who moved to greener areas. Their mean inverse scores rose progressively from 9.78 two years prior to the move, to 10.10 a year after the move to greener areas, and stayed there for the next two years, suggesting an improvement that was sustained.

Adding an outdoor component to typical interventions for mental health, such as cognitive-behavioral therapy (CBT), augmented the positive results of the intervention. Kim et al (2009) undertook to compare the efficacy of CBT for major depression in hospital versus forest settings and a control group.

They found that the participants that had undergone CBT in a natural setting had significantly lower depressions scores (mean

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score of 8.04 on the Hamilton Rating Scales for Depression in the forest group versus 11.58 in the hospital group and 14.81 in the control group), and significantly higher remission rates (61% in the forest group versus 21% and 5% in the hospital and control groups, respectively).

The additive benefit effect is similar to what was found with outdoor versus indoor exercise.

Nature increases cognitive performance and memory The health of children has changed with the advent of modern technology as much as adults’ has. Disorders such as ADHD are more prevalent, and children spend increasingly more time with ‘screens’ indoors. Whether screen time and ADHD are truly connected or not, time in nature seems to be good for both.

Several studies have looked at the potential use of ‘green space play’ to improve symptoms of ADHD. One such study by Taylor et al (2001) surveyed parents of children diagnosed with ADHD with a specially designed questionnaire.

They asked about their kids’ attention and behaviour symptoms following play in various settings, and asked to rank which type of play resulted in the best and worst overall behaviour: a green setting (eg. fishing, soccer), an ambiguous setting (eg. rollerblading, playing outside), or a non-green setting (eg. video games). The findings displayed that green play significantly reduced ADHD symptoms when compared to non-green play.

Spending time in a natural setting can also aid in the recovery of cognitive functions after they have been taxed. In a 2003 trial

by Hartig and colleagues, participants had to perform either a mentally taxing activity or a take a non-taxing drive to a field site.

Each group was then divided and assigned to spend time in an urban environment or a natural one. The researches measured blood pressure, affect, and performance on a memory test. The participants that got to recover in the natural setting, regardless of the initial task, had a faster decrease in blood pressure, and better performance on the memory test.

Berman et al (2008) did a similar study, and suggest that the reason for improved cognitive recovery in natural settings is that nature is less psychologically demanding and invokes a state of peacefulness. An urban setting demands more attention that in turn is cognitively taxing.

Nature boosts immune activity Stress hormones can compromise immune function by suppressing the action of natural killer cells. Evergreen trees, prominent in our boreal forests, secrete chemicals collectively known as phytoncide. Phytoncide is associated with improvements in human immune cell activity, particularly with enhancing human natural killer (NK) cell activity, the number of NK cells, intracellular anti-cancer proteins in lymphocytes, and significantly decreasing the concentrations of adrenaline and noradrenaline in urine. What’s even more fascinating, is that in a 2009 study conducted by Li et al, the increased NK activity measured with both blood and urine samples lasted for more than seven days after trips to forests both in male and female subjects (Li 2009).

Nature reduces cardiovascular risk Cardiovascular disease and risk factors are all too prevalent in primary care, therefore it becomes important to have a wide arsenal of recommendations. A research team out of China (Mao et al 2012), conducted a study to investigate the effect of natural spaces on cardiovascular biomarkers. Twenty-four comparable elderly participants with essential hypertension were divided into two groups, one spent a day walking in the city, and the other in a national forest in similar, controlled manners. The team measured blood pressure, heart rate, and pulse pressure, as well as running assays to track any changes in interleukin-6 (IL6), tumor necrosis factor alpha (TNF-a), endothelin-1, homocysteine, renin, angiontensinogen (AGT), angiotensin II, angiotensin II type 1 receptor (AT1), and angiotensin II type 2 receptor (AT2). Not all the markers responded in a significant manner, yet there were some significant changes that may be surprising given that they only intervention was simply walking in a forest. Compared to the city group, those who walked in the forest had significantly lower blood pressure - by about 8 systolic points and 3 diastolic points.

Endothelin-1, homocysteine, AGT, AT1, and AT2 were also significantly lower in the forest group.

These serum factors are closely associated with essential hypertension. It is yet unclear if these kinds of effects are short-lived and limited to the time spent in nature or whether the changes endure. At the very least a natural setting offers a respite for the cardiovascular system.

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Li et al (2011) have found similar results with respect to the hypertension reducing effects, as have Tsunetsugu et al more recently (2013). The explanation as to why spending time in nature has such a reproducible effect on blood pressure is multi-factorial.

Tsunetsugu’s team has demonstrated that there is an increase in parasympathetic nervous system activation, and a decrease in sympathetic activation, a decrease in cortisol levels, and an increase in subjective relaxation, all blood pressure reducing factors.

Conclusions Naturopathic medicine originated in the ‘nature cure’ traditions of European healers, to whom spending time in nature was a mandatory part of providing natural health care. Many of those traditions have been preserved in naturopathic philosophy, but as the modern North American lifestyle prevailed, the need to connect to nature has been somewhat lost. As confirmation of the beliefs of naturopathic forefathers, the evidence that has been summarized here and the research being conducted currently, highlight the importance health benefits that result from being in touch with natural spaces.

More research studies need to be conducted on this important topic as much of the existing research is cross-sectional, References Alcock I, White MP, Wheeler BW, Fleming LE, Depledge MH. Longitudinal effects on mental health of moving to greener and less green urban areas.

Environ Sci Technol. 2014; 48(2):1247-55 Barton J, Pretty J. What is the Best Dose of Nature and Green Exercise for Improving Mental Health? A Multi-Study Analysis. Environ. Sci. Technol.

2010; 44:3947–3955.

Berman MG, Jonides J, Kaplan S. The cognitive benefits of interacting with nature. Psychol Sci. 2008;19(12):1207-12.

Beyer KM, Kaltenbach A, Szabo A, Bogar S, Nieto FJ, Malecki KM. Exposure to Neighborhood Green Space and Mental Health: Evidence from the Survey of the Health of Wisconsin. Int J Environ Res Public Health. 2014; 11(3): 3453–3472 Coon JT, Boddy K, Stein K, Whear R, Barton J, Depledge MH. Does Participating in Physical Activity in Outdoor Natural Environments Have a Greater Effect on Physical and Mental Wellbeing than Physical Activity Indoors? A Systematic Review. Environmental Science & Technology, 2011; 45(5): 1761–1772 Downey L, Strife S. Childhood Development and Access to Nature. A New Direction for Environmental Inequality Research. Organ Environ. 2009; 22(1): 99–122.

Hartig T, Evans GW, Jamner LD, Davis DS, Garling T. Tracking restoration in natural and urban field settings. Journal of Environmental Psychology. 2003; 23(2):109-123 Kim W, Lim SK, Chung EJ, Woo JM. The effect of cognitive behavior therapybased psychotherapy applied in a forest environment on psychological changes and remission of major depression. Psychiatry Invest. 2009; 6: 245–254 Li Q, Kobayashi M, Wakayama Y, Inagaki H, Katsumata M, Hirata Y,

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observational, or have low sample sizes. Nonetheless, none of the evidence and conclusions have been mixed - they all show a positive relationship between biomarkers of health and nature.

These studies have confirmed that spending time in nature can reduce psychological and physical stress, symptoms of depression and negative affect, while improving sleep quality and increasing feelings of liveliness and relaxation. Objective data researched in more than a dozen studies shows that forest walking decreases stress hormone levels, lowers blood pressure and heart rate, and positively impacts immune function (Logan 2012).

Considering that the level of risk is very low, especially relative to benefit, combined with a growing body of evidence, it is suggested that using nature as an opportunity for physical exercise, contemplation and mindfulness be part of your physician’s prescription. Contact with green space is thought to be even more beneficial to those populations that are most at risk due to lower socioeconomic status and living in urban environments (Downey and Strife 2009). We conclude therefore that “Vitamin G” should make its way back to the prescription pads of all practicing health providers, particularly for those patients with high levels of stress, hypertension, sedentary lifestyles, and mental health concerns. ■ Hirata K, Shimizu T, Kawada T, Park BJ, Ohira T, Kagawa T, Miyazaki Y. Effect of phytoncide from trees on human natural killer cell function. Int J Immunopathol Pharmacol. 2009; 22(4): 951-9.

Logan A, Selhub E. Your Brain On Nature: The Science of Nature’s Influence on Your Health, Happiness, and Vitality. Mississaugua, ON: John Wiley & Sons Canada Publisher, 2012.

Louv R. Last Child in the Woods. Saving Our Children From Nature-Deficit Disorder. Chapel Hill, NC: Algonquin Books Of Chapel Hill, 2005.

Mao GX, Cao YB, Lan XG, He ZH, Chen ZM, Wang YZ, Hu XL, Lv YD, Wang GF, Yan J. Therapeutic effect of forest bathing on human hypertension in the elderly. Journal of Cardiology. 2012; 60(6): 495-502 Park BJ, Tsunetsugu Y, Kasentani T, Hirano H, Kagawa T, Sato M, Miyazaki Y. Physiological Effects of Shinrin-yoku (Taking in the Atmosphere of the Forest)—Using Salivary Cortisol and Cerebral Activity as Indicators. J Physiol Anthropol. 2007; 26(2): 123–128.

Roe JJ, Thompson CW, Aspinall PA, Brewer MJ, Duff EI, Miller D, Mitchell R, Clow A. Green space and stress: evidence from cortisol measures in deprived urban communities. Int J Environ Res Public Health. 2013; 10(9): 4086-103 Taylor AF, Kuo FE, Sulllivan WC. Coping with ADD: The surprising connection to green play settings. Environment and Behavior, 2001; 33(1), 54–77.

Tsunetsugu Y, Lee J, Park BJ, Tyrvainen L, Kagawa T, Miyazaki Y. Physiological and psychological effects of viewing urban forest landscapes assessed by multiple measurements. Landscape and Urban Planning. 2013; 113: 90-93 Vogelzangs N, Beekman A, Milaneschi Y, Bandinelli S, Ferrucci L and Penninx B. Urinary cortisol and six-year risk of all-cause and cardiovascular mortality. J Clin Endocrinol Metab. 2010; 95(11): 4959–4964.

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Maintaining your memory Natural products that support early cognitive decline and dementia

By Ronald G Reichert, ND

2 Ronald G Reichert, ND Gastown Physio Pilates 306- 560 Beatty St, Vancouver, BC, V6R 2L3 docr@shaw.ca

Abstract With the aging North American demographic, dementia is projected to become a prevalent condition, affecting over 115 million adults by the year 2050. Given the impact that this condition has on all areas of health, including mental, emotional, and physical function, as well as the ability to live independently, it is critical to find better treatments for management. A number of nutraceutical agents have been studied in this population of patients, and have been shown to exert beneficial effects for mild cognitive impairment as well as dementia. These include L-theanine, green tea, huperzine A, Ginkgo biloba, Crocus sativa, ginseng, acetyl-L-carnitine, choline, as well as B-vitamins. This paper is a review of the current evidence in this area.

Introduction Dementia is a looming public health crisis. In a 2012 report, the World Health Organization noted that the current number of individuals living with dementia worldwide is estimated at 35.6 million. Alarmingly, this number is expected to double by 2030 to 65.7 million and more than triple to 115.4 million in 2050 (WHO 2012). Statistics released from the Alzheimerâ&#x20AC;&#x2122;s Society of Canada corroborate this worldwide trend. In 2011, 747,000 Canadians aged 65 years and older were living with cognitive impairment. This figure is expected to increase to 1.4 million by 2031 (ASC 2014). Despite these daunting statistics, targeted herbal medicines, nutritional supplements, and food can all be of value to the clinician and their patients who are dealing with early cognitive decline and mild to moderate dementia.

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Let Food Be Your Medicine: “Juicing” Your Memory Polyphenols as found in for example apples or grape, have significant antioxidant and neuroprotective effects that are of value in the treatment of Alzheimer’s (Bhullar 2013). In an open label clinical trial, 21 patients with moderate to severe Alzheimer’s dementia were given two 4-ounce glasses of apple juice daily for one month. No cognitive changes were noted in either the Dementia Rating Scale or the Alzheimer’s Disease Cooperative Study (ADCS)-Activities of Daily Living (ADL). However, using the Neuropsychiatric Inventory (NPI) as a measure of behavioral and psychotic symptoms, caregivers reported an approximate 27% (P< 0 .01) improvement (especially anxiety, agitation, and delusion) in dementia associated symptoms (Remington 2010). In another controlled trial, 12 older adults (mean age 78.2 years) with cognitive decline (but not dementia) were randomised to receive 6 to 9 ml/kg of Concord grape juice or placebo for 12 weeks. Those consuming the polyphenol rich grape juice had a significant improvement in verbal learning as measured by the California Verbal Learning Test (p=0.04).

While there was no change on body weight, waist circumference, and fasting glucose levels, there was a significant increase in fasting insulin levels (p=0.03) (Krikorian 2010). The increase in fasting insulin levels could be of potential concern since insulin resistance triggers a profoundly injurious metabolic milieu within neuronal tissues, leading an increase of toxic amyloid beta protein along with neurofibrillary tangles and plaques in the brain (Farias 2009, Lin 2014, Sato 2014). However, in addition to the potential therapeutic benefit of polyphenols, several types of herbal medicines provide additional clinical assistance for those with age related neurodegenerative disorders including L-theanine and Green tea.

Phytotherapy and Mild Cognitive Impairment (MCI) L theanine and Green tea for MCI In those diagnosed with MCI, it is estimated that 10 to 15% of subjects progress to Alzheimer’s Dementia (de la Monte 2014). In one study, 91 elderly Korean subjects (25 men, 66 women) with mild cognitive impairment (average age 57.58 years) were randomized to receive two 420 mg capsules twice per day of a Green tea/L-theanine extract (each capsule 360 mg green tea extract and 60 mg L-theanine), for a total of 1680mg per day, given 30 minutes after meals or placebo daily for 16 weeks. Those employing the herbal combination 60

and with an initial Mini Mental State Exam Scores (MMSE-K) between 21-23 showed a significant increase in memory and selective attention at 16 weeks as measured by the Rey-Kim memory quotient (p=0.0478). Moreover, this latter group also experienced an improvement in the Stroop word colour reading test (a measure of selective attention) at eight weeks compared to placebo (p=0.0306) (Park 2011).

Huperzine A for Vascular Dementia Huperzine A, a cholinesterase inhibiting alkaloid from the plant Huperzia serrata, has been shown to be of value in treating vascular dementia (Ha 2011). In a controlled study, 78 patients (28 women, 50 men; average age 71.8 to 72.3 years) with mild to moderate vascular dementia were randomized to receive either huperzine A (0.1 mg twice a day) or, placebo (vitamin C 100mg twice day) for 12 weeks. Using a battery of standardized tests, those employing the huperzine A had significant improvements in their cognitive function (i.e. memory, language, and visual spatial abilities) as measured by MMSE scores along with improvements in Clincial Dementia Rating (CDR) scores and Activity of Daily Living Scores (ADL) compared to placebo (p< 0.01). Side effects were minimal with only one participant in the active group noting some transient nausea and dizziness (Xu 2012). An in vivo study has shown that huperzine A therapy not only decreases beta amyloid levels and reduces amyloid plaque formation but also reduces iron content in the brain (Huang 2014). Iron, a pro-oxidant metal, may accelerate beta amyloid activity (Cahill 2009, Schubert 1995).

Ginkgo biloba: Clinical Value in the Active Treatment of Dementia While long term use of the herb Ginkgo biloba does not reduce the risk of progression to Alzheimer’s disease, it is still a valuable agent in the treatment of mild to moderate dementia (Vellas 2012). In a multi-centre, double-blind, placebo-controlled study, 410 patients with mild to moderate dementia (Alzheimer`s or vascular dementia) were randomized to receive a standardized extract from Ginkgo biloba leaves 240 mg once daily or placebo for 24 weeks. Clinically significant improvements in cognition and behaviour as measured by the Syndrom-Kurz test (SKT) and the NPI were noted more frequently in those treated with Ginkgo biloba (SKT: +43%, NPI: 57%) compared to those taking the placebo (SKT: 23%, NPI: 39%) (p< 0.001) (Herrschaft 2012).

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Saffron (Crocus sativus): As Good as the Drug Donepezil?

While the herb Ginkgo biloba has shown comparable efficacy to the anti-cholinesterase drug donepezil (Mazzaa 2006), research suggests that saffron may also be comparable to drug therapy in Alzheimer’s. Fifty-four adults (29 men; 25 women; average age 72.70 years) with mild to moderate dementia, were randomized to receive a capsule of Crocus sativus stigma 30 mg/ day (15 mg twice per day) or donepezil 10 mg/day (5 mg twice per day) for 22 weeks. Each saffron capsule was standardized to contain 0.13–0.15 mg safranal and 1.65–1.75 mg crocin. At the conclusion of the clinical trial, both saffron and donepezil were comparable in efficacy. Both saffron and donepezil decreased Alzheimer’s Disease Assessment Scale (ADAS-cog) scores compared to baseline by −3.96± 3.50 and −3.77±3.80 respectively (Akhondzadeh 2010). Safranal accounts for the unique odour of saffron and has several pharmacological properties including anticholinesterase activities (Rezaee 2013). Crocin, a carotenoid responsible for the colour of saffron, has several reported actions including antioxidant and antidepressant (Alavizadeh 2014).

Ginsenosides for Dementia?

Animal studies suggest that ginsenosides, especially RB1, seem to increase the release of acetylcholine from the hippocampus and reduce the toxic neurological effects of beta-amyloid peptide (Heo 2008). In an prospective open label study, 97 Alzheimer’s patients (47 to 83 years of age) randomized to receive 4.5 grams per day Panax ginseng powder or control for 24 weeks. Ginseng was discontinued at 12 weeks with a further follow-up at 24 weeks. Cognitive performance as measured by ADAS-Cog (p< 0.05) and MMSE (p< 0.01) improved significantly by week 12 (Lee 2008). In addition, to herbal medicines like Ginseng, there are several types of nutritional supplements that have been proven to be of value in the clinical treatment of dementia beginning with Acetyl L Carnitine.

Nutraceuticals for Dementia Acetyl L Carnitine and Dementia While the precise mechanism for the action of Acetyl L Carnitine (ALCAR) is not well understood, researchers have suggested that it may facilitate acetylcholine production through neural synaptic stimulation (Editor 1999). Although a meta-analysis has concluded that ALCAR is not an important therapeutic agent in the treatment of dementia (Hudson 2003), single clinical trials have demonstrated otherwise. In one double-blind, placebocontrolled pilot study, 30 patients (60 to 80 years of age) with mild to moderate Alzheimer’s disease were randomly assigned to receive ALCAR at a dose of 2.5 grams per day for three months followed by an increase to 3 grams per day for another three months in divided doses or placebo. At the conclusion of the trial and in contrast to placebo, the ALCAR group had significant improvement on the Cancellation task and Digit Span (forward) tests (p<0.05). In a subgroup of patients who scored low on the MMSE, there was a significant improvement in memory in those taking the active substance (as noted by

Verbal Selective Reminding Test (+1.8%) than those taking the placebo medication (- 54%). This latter information prompted the researchers to note that ALCAR was effective in moderate Alzheimer’s and not milder cases (Sano 1992).

Choline alfoscerate and Alzheimer’s Like ALCAR, a derivative of phosphatidylcholine called choline alfoscerate (L-alpha-glycerylphosphorylcholine), has been shown in vivo to increase acetylcholine in the hippocampus (Amenta 1993).

In a multicenter, double-blind, placebo-controlled trial, 261 patients (199 women; 62 men 60 to 80 years of age) with mild to moderate dementia of the Alzheimer type were randomized to receive choline alfoscerate capsules 400 mg three times a day or placebo for six months. After 180 days, those employing the active substance had an average decrease in ADAS-cog scores by 3.20 points compared to an increase in placebo by 2.90 points (p<0.001 versus baseline).

Secondary measures such as MMSE scores also improved in the active group by 6.33 points compared to a reduction by 0.50 in the placebo group at the six-month mark (p< 0.001) (De Jesus 2003).

Homocysteine, B-vitamins and MCI One group of researchers has suggested that elevations in homocysteine have been shown to accelerate brain grey matter atrophy and, that the use of B-vitamins reduces atrophy in that vulnerable region of brain as much as seven fold (Douaud 2013).

In a long term double-blind, single-centre study, 266 participants (greater than 70 years of age) with mild cognitive impairment were randomly assigned to receive a daily dose of 0.8mg folic acid, 0.5mg vitamin B12 and 20mg vitamin B6 or placebo for two years. Overall, the use of B-vitamins helped support executive and planning functions (CLOX, the Executive Clock Drawing Task) relative to placebo (P=0.015) treatment. B vitamins were of significant value in those with homocysteine value above the median (11.3 mmol/L) in several neuropsychiatric measures including global cognition (MMSE; p<0.001), episodic memory (Hopkins Verbal Learning Test–delayed recall, P=0.001) and semantic memory (category fluency, p=0.037) (de Jager 2012).

Natural Products Do Make a Difference in Dementia Outcomes In the treatment of dementia, the integrated practitioner has numerous options available to them ranging from food to herbal medicines to nutritional supplements. A combination of foundational diet strategies aimed at improving metabolic defects such as hyperinsulinemia and insulin resistance, combined with use of nutritional or herbal agents that can favourably alter neuronal mitochondrial function, cerebro-circulatory function, acetylcholine (Ach) production, and antioxidant defenses is expected to yield considerable, synergistic clinical effects. Since pharmaceutical treatment of mild cognitive impairment and dementia is limited, and given the high safety profile of these natural medicines, diet- and NHP- based strategies do have a key role to play in the treatment and prevention of dementia, and should be part of the overall approach in this burgeoning public health crisis. ■ October 2014 | www.ihpmagazine.com

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References Akhondzadeh S, Mehdi SS, Harirchian MH et al . A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer’s disease. Psychopharmacol. 2010: 207:637–643.

Alavizadeh SH, Hosseinzadeh H. Bioactivity assessment and toxicity of crocin: a comprehensive review. Food Chem Toxicol. 2014;64:65-80.

Alzheimer Society Canada (ASC). Facts about dementia. Updated 20 June 2014. http://www.alzheimer.ca/en/About-dementia/Dementias/What-isdementia/Facts-about-dementia Accessed 22 September 2014.

Amenta F, Franch F, Ricci A, Vega JA. Cholinergic neurotransmission in the hippocampus of aged rats: influence of L-alpha-glycerylphosphorylcholine treatment. Ann N Y Acad Sci. 1993 Sep 24;695:311-3.

Bhullar KS, Rupasinghe HP. Polyphenols: multipotent therapeutic agents in neurodegenerative diseases. Oxid Med Cell Longev. 2013;2013:891748.

Cahill CM, Lahiri DK, Huang X, Rogers JT. Amyloid precursor protein and alpha synuclein translation, implications for iron and inflammation in neurodegenerative diseases. Biochim Biophys Acta. 2009;1790:615-28. de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry.

2012; 27:592–600.

De Jesus Moreno Moreno M. Cognitive improvement in mild to moderate Alzheimer’s dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebocontrolled trial. Clin Ther. 2003 Jan;25(1):178-93. de la Monte SM, Tong M. Brain metabolic dysfunction at the core of Alzheimer’s disease. Biochem Pharmacol. 2014;88:548-59.

Douaud G, Refsum H, de Jager CA, Jacoby R, Nichols TE, Smith SM, Smith AD. Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci U S A. 2013;110:9523-8.

Editor. Acetyl L Carnitine Monograph. Alt Med Rev 1999;4:438-441.

Farias ST, Mungas D, Reed BR, Harvey D, DeCarli C. Progression of mild cognitive impairment to dementia in clinic- vs community-based cohorts.

Arch Neurol. 2009;66:1151-7.

Ha GT, Wong RK, Zhang Y. Huperzine a as potential treatment of Alzheimer’s disease: an assessment on chemistry, pharmacology, and clinical studies. Chem Biodivers. 2011;8:1189-204.

Heo JH, Lee ST, K. Chu, MJ, Oh J, Park HJ, Shim JY, Kim M. An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimer’s disease. Eur J Neurol.

2008;15:865-868.

Herrschaft H, Nacub A, Likhachev S, Sholomov I, Hoerr R, Schlaefke S. Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: A randomised, placebo-controlled trial to confirm the efficacy and safety of a daily dose of 240 mg. J Psych Res. 2012:46:716-723.

Hudson S, Tabet N. Acetyl-L-carnitine for dementia. Cochrane Database Syst Rev. 2003;(2):CD003158.

Krikorian R, Nash TA, Shidler MD, Shukitt-Hale B, Joseph JA. Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr. 2010;103:730-4.

Lee ST, Chu K, Sim JY, Heo JH, Kim M, Panax Ginseng Enhances Cognitive Performance in Alzheimer Disease. Alzheimer Dis Assoc Disord.

2008;22:222–226.

Lin F, Jia J, Qin W. Enhancement of β-amyloid oligomer accumulation after intracerebroventricular injection of streptozotocin, which involves central insulin signaling in a transgenic mouse model. Neuroreport. 2014 Nov 12;25(16):1289-95.

Mazzaa S, Capuanob, A, Bria P, Mazza S. Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer’s dementia in a randomized placebo-controlled double-blind study. Euro J Neurol. 2006;13:981–985.

Park SK, Jung IC, Lee WK, Lee YS, Park HK, Go HJ, Kim K, Lim NK, Hong JT, Ly SY, Rho SS. A combination of green tea extract and l-theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebo-controlled study. J Med Food. 2011 Apr;14(4):334-43.

Remington R, Chan A, Lepore A, Kotlya E, Shea TB. Apple juice improved behavioral but not cognitive symptoms in moderate-to-late stage Alzheimer’s disease in an open-label pilot study. Am J Alzheimers Dis Other Demen.

2010;25:367-71.

Rezaee R, Hosseinzadeh H. Safranal: from an aromatic natural product to a rewarding pharmacological agent. Iran J Basic Med Sci. 2013;16:12-26.

Sano M, Bell K, Cote L, Dooneief G, Lawton A, Legler L, Marder K, Naini A, Stern Y, Mayeux R. Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer’s disease. Arch Neurol.

1992;49:1137-41.

Sato N, Morishita R. Brain alterations and clinical symptoms of dementia in diabetes: aβ/tau-dependent and independent mechanisms. Front Endocrinol (Lausanne). 2014 Sep 5;5:143.

Schubert D, Chevion M.The role of iron in beta amyloid toxicity. Biochem Biophys Res Commun. 1995;216:702-7.

Vellas B, Coley N, Ousset PJ, Berrut G, Dartigues JF, Dubois B, Grandjean H, Pasquier F, Piette F, Robert P, Touchon J, Garnier P, Mathiex-Fortunet H, Andrieu S; GuidAge Study Group. Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer’s disease (GuidAge): a randomised placebo-controlled trial. Lancet Neurol. 2012;11:851-9.

World Health Organization (WHO) and Alzheimer’s Disease International.

Dementia: a public health priority. Updated 2012. URL: http://apps.who.int/ iris/bitstream/10665/75263/1/9789241564458_eng.pdf?ua=1 Accessed 22 September 2014.

Xu ZQ, Liang XM, Juan-Wu, Zhang YF, Zhu CX, Jiang XJ. Treatment with Huperzine A improves cognition in vascular dementia patients. Cell Biochem Biophys. 2012 Jan;62(1):55-8.

Huang XT, Qian ZM, He X, Gong Q, Wu KC, Jiang LR, Lu LN, Zhu ZJ, Zhang HY, Yung WH, Ke Y. Reducing iron in the brain: a novel pharmacologic mechanism of huperzine A in the treatment of Alzheimer’s disease. Neurobiol Aging. 2014;35:1045-54.

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The Very Best Nutrients for Mother & Baby P

regnant mothers want what’s best for themselves and their growing baby. For over 20 years, pregnant and nursing mothers have trusted Carlson PreNatal supplements to provide them with the essential vitamins and minerals they needed during this special time. Carlson’s PreNatal Multiple is an easy-to-swallow soft gel with the added benefits of DHA. DHA is an important omega-3 that is vital to baby’s development. Recent medical studies have found that DHA supplementation is especially important during pregnancy and lactation because DHA helps support the development of an infant’s brain and eyes during pregnancy and, when taken after pregnancy, can enhance the quality of a mother’s breast milk.

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PRODUCT MONOGRAPH Prenatal Multiple with DHA Carlson Prenatal Multiple with DHA is specially formulated for the unique nutritional needs of pregnant and nursing mothers. Each easy-to-swallow soft gel provides 22 vitamins and minerals as well as the important long chain polyunsaturated omega-3, DHA. Emerging scientific research suggests that DHA is vitally important for women both during and after pregnancy because it helps support brain, nerve, vision, immune, and cardiovascular systems, as well as healthy skin.

DHA is a building block of the eyes and the brain.

A woman’s nutritional needs are higher during pregnancy that at any other period of her life.

The daily requirements for most of the essential vitamins and minerals are increased during pregnancy, generally to provide the developing fetus with the required nutrients and to provide the extra energy that is required by the mother for lactation. 1 Folic acid, iron, vitamin B 12, zinc and calcium are needed in greater amounts during pregnancy, and these are nutrients whose intake is often found to be deficient in pregnant women. Because vitamin B 12 is found only in foods of animal origin, the American Dietetic Association recommends that vegans and lacto-ovo vegetarians take supplemental vitamin B 12.2 Folic acid is needed for the formation of new red blood cells and the development of the central nervous system. Insufficient intake of this important B vitamin can cause anemia, low birth weight babies, and neural tube birth defects, such as spina bifida.3 Vitamin D, also known as “the sunshine vitamin”, helps calcium absorption and promotes healthy bones and teeth. It supports the nervous system, immune function and is especially important during pregnancy. Vitamin D deficiency is thought to be common among pregnant women, particularly during the winter months, and has been found to be associated with an increased risk of pre-eclampsia, gestational diabetes mellitus, preterm birth, and other tissuespecific conditions. Fetal needs for vitamin D increase during the latter half of pregnancy, when bone growth and ossification are most prominent. Vitamin D travels to the fetus by passive transfer, and the fetus is entirely dependent on maternal stores. 4 During pregnancy, iron is required for red blood cell expansion in both the mother and the fetus.

Extra iron is needed, particularly if the mother’s iron stores are not optimal prior to pregnancy.

The developing fetus requires sufficient stores because soon after birth there is a significant decrease in the infants’ iron stores. Carlson Prenatal Multiple with DHA is nutritionally balanced for the requirements of the expecting mother and supplies her baby with the proper nutrients required for healthy development.

Carlson Laboratories award-winning fish oil products are renowned for their purity. All Carlson fish oil products are regularly tested for freshness, potency, and purity by an independent, FDAregistered laboratory.

Public Health Agency of Canada. (2008). The Sensible Guide to a Healthy Pregnancy.

Available at: www.healthycanadians.ca/pregnancy 1

Kaiser L, Allen LH. Position of the American Dietetic Association: nutrition and lifestyle for a healthy pregnancy outcome. J Am Diet Assoc. 2008;108(3):553-561.

3 Food and Nutrition Board, Institute of Medicine. Folate. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, D.C.: National Academy Press; 1998:196-305.

4 De-Regil M et al Vitamin D supplementation for women during pregnancy. Cochrane Database of Systematic Reviews, 2012, (2): CD008873.

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The Journal of IHP

Nutritional, Nutraceutical, and Herbal Supplements in the Treatment of Inflammatory Bowel Disease A review

Sukriti Bhardwaj , Ivana Camposilvan , Christine Chung , Everett Claridg , Matthew Lee , Calum Scott , Jordan Robertson1,2,3 1

1

1 | Bachelor of Health Sciences (Honours), McMaster University

Abstract

2 | Associate Faculty, Bachelor of Health Sciences Program, McMaster University 3 | Naturopathic Doctor, Canadian College of Naturopathic Medicine

1

e1

1

1

Complimentary therapies for inflammatory bowel disease are a growing interest, with goals of maintaining remission and reducing the need for more aggressive conventional treatments. Although widely utilized by patients, limited and heterogeneous research has complicated the clinical decision to rely on alternative care for effective disease management. Here we present the most relevant, up to date information regarding the use of herbs, fish oil, probiotics and vitamin D for the treatment of both Crohn’s and Ulcerative Colitis, which will aide clinicians in choosing the most effective collaborative treatment based on their patient’s symptoms and disease state.

3

Introduction In Canada, the incidence rate has increased to 10 200 people being diagnosed with inflammatory bowel disease (IBD) each year (Crohn’s and Colitis Foundation of Canada 2013). Crohn’s Disease (CD) and Ulcerative Colitis (UC), two major forms of idiopathic IBD, are characterized by chronic and uncontrolled inflammation within the gastrointestinal tract. Currently, 233 000 Canadians are living with IBD with direct medical costs totaling over $2 billion dollars each year (Rocchi 2012). Conventional therapies such as immunomodulators and 5-aminosalicylic acid (5-ASA) have shown adverse effects (i.e. interstitial nephritis) and have caused patient drop-out rates as high as 22% (Jonkers 2012, Siegel 2005).

In addition, approximately 38% of patients treated with 5-ASA are non-responders (Duricova 2010, Gisbert 2002).

Increased recognition of the limitations in conventional medicine has led to growing interests in integrative therapies by patients with IBD (Hilsden 2011). Several studies indicate that supplements are a widely used type of complementary and alternative medicine (CAM) among IBD patients (Hilsden 2011, Sutherland 1994). Limited research and lack of education surrounding the use of CAM makes it difficult for health care professionals to effectively counsel patients regarding the use of supplements in IBD (Hilsden 2011). Given their widespread usage, health care practitioners should be familiar with the potential benefits of nutraceutical supplements for IBD to offer superior care to their patients (Hilsden 2011).

The present paper will investigate the mechanisms of action and clinical effectiveness of several well-documented supplements in managing IBD. The supplements to be examined include Aloe vera, Andrographis paniculata,Bboswellia serrata, Curcuma longa, fish oil, probiotics, and vitamin D. October 2014 | www.ihpmagazine.com

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Mechanism of IBD The etiology of IBD is unknown. Normally, mucosal immune cells within the intestinal epithelium discriminate commensal from pathogenic bacteria, however those afflicted with IBD are unable to discern between the two (Friedman 2012). Instead, an inappropriate immune reaction is levied against the commensal bacteria leading to elevated levels of pro-inflammatory cytokines and chemokines including tumor necrosis factor-alpha (TNFα), interferon-gamma (INF-γ), and interleukin1-beta (IL-1β) (Friedman 2012). For example, compared to healthy controls, there is a significant difference in serum TNF-α concentration in CD and UC patients, resulting in chronic mucosal damage (Avdagic 2013, Friedman 2012). Furthermore, reactive oxygen species produced by activated neutrophils result in the damage of mucosal proteins in patients with IBD (McKenzie 1999).

Mechanisms of Conventional Medicine in IBD 5-ASA is a well-established therapy in the management of UC, but its role in CD is less clear (Criscuoli 2013). The antiinflammatory and immunosuppressive properties of 5-ASA provide evidence for a multifactorial basis of therapeutic action (Baumgart 2005). A primary target is the nuclear factor kappa beta (NF-κβ) pathway. NF-κβ is normally maintained in an inactive state by inhibitory protein kappa-beta (Iκβ). In patients with IBD, however, the presence of pro-inflammatory cytokines such as TNF-α, phosphorylation of Iκβ activates NFκβ, initiating the synthesis of more pro-inflammatory cytokines (Jobin 2000). 5-ASA has been shown to inhibit TNF-α-stimulated Iκβ phosphorylation, disrupting a critical signal transduction pathway involved in the onset and progression of chronic inflammation (Fang 1999).

The supplements to be examined target similar pathways as 5-ASA and primarily influence the progression of IBD through reduction of the aforementioned pro-inflammatory cytokines. Thus, their use as alternatives for non-responders to conventional medicine is implicated.

Herbal Medicine The perceived natural properties of herbal therapies have led to increased use of such therapies by patients with IBD (Hilsden 2011). In the present paper, four notable herbal therapies, namely Aloe vera gel, Andrographis paniculata, Boswellia serrata, and Curcuma longa, will be evaluated.

Aloe vera gel, an extract of Aloe barbadensis, is a common herbal therapy used in the treatment of IBD (Hilsden 2003, Rahimi 2009). A double-blind, randomized controlled trial (RCT) showed that four weeks of aloe vera gel administration to patients with active UC had greater symptom alleviation than placebo. This difference, however, was not statistically significant (p=0.09) (Langmead 2004).

A. paniculata, namely andrographolide, has been shown to significantly reduce the transcriptional activity of NF-κβ and decrease secretions of pro-inflammatory cytokines including TNF-α and IL-6, both of which have been shown to be elevated in patients with IBD (Chao 2010, Chiou 2000). A double-blind 66

RCT (n=224) reported greater clinical response in UC patients receiving A. paniculata treatment than placebo, which is characterized as a decrease in the total Mayo score of three points and 30% accompanying decrease in rectal bleeding (Sandborn 2013). Similar results were reported in a clinical trial comparing the efficacy of A. paniculata to conventional mesalazine therapy (Tang 2011).

Animal models suggest boswellic acids, the active component of Boswellia serrata, mitigate leukocyte recruitment thereby protecting the intestinal mucosa from the inappropriate immune reaction characteristic of IBD (Anthoni 2006, Hartmann 2012). Two notable studies compared B. serrata extract (BSE), given as 400mg capsules, against placebo in patients with IBD. Madisch (2007) found a statistically significant difference in remission rates between BSE and placebo groups in patients with collagenous colitis was found. However, in a 52 week trial, Holtmeier and colleagues (2011) found that remission rates were not statistically significant between control and treatment groups (p=0.85). Nevertheless, BSE treatment was shown to be well tolerated and demonstrated long term safety as Holtmeier (2011) reported that those treated with BSE experienced less adverse events than those treated with placebo (p=0.087).

Though the aforementioned herbal therapies have yielded greater rates of remission and clinical response compared to placebo in the management of IBD, failure to reach statistical significance warrants additional research to evaluate their effectiveness, perhaps at greater dosages and with larger sample sizes (Langmead 2004, Sandborn 2010, Sandborn 2013).

Historically, Asian countries experience approximately half the incidence rate of IBD seen in North American countries (Loftus 2004). This can be attributed to the prevalence of Curcuma Longa in the traditional diet in Asian countries and has been shown to improve colonic morphology by counteracting the generation of damaging reactive oxidative species (ROS) produced by inflamed colon cells (Irving 2011). Additionally, Curcumin inhibits the secretion of inflammatory cytokines by modulating the activation of NF-κβ, an upregulated in patients with IBD (Atreya 2008,).

Curcumin suppresses NF-κβ activation by blocking the phosphorylation of inhibitory factor Iκβ kinase, downregulating the expression of downstream pro-inflammatory eicosanoids (Atreya 2008). Curcumin has also been found to block the action of proinflammatory TNF-α primarily through inhibiting the production of TNF transcription factors leading to transcriptional repression (Aggarwal 2013). In a pilot study of five patients with UC and five with CD, all patients improved over the two month period of Curcumin administration (Holt 2005). For both conditions, diarrhea, abdominal pain, and cramping decreased, and previously elevated serologic indexes of inflammation normalized. However, a major limitation of this study was the absence of a control group. In another multicenter RCT, patients administered with Curcumin in conjunction with 5-ASA saw significantly improved symptoms compared to placebo with 5-ASA. Patients treated with Curcumin also had a lower relapse rate six months post-study (Hanai 2006).

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The Journal of IHP

Furthermore, a prospective phase-1 study in adults using a significantly high dose of Curcumin to treat cancer (8 g/day), found no toxic effect (Cheng 2001), validating the safety of the dosage used to treat IBD.

Fish Oil Dietary fat composition affects the immune responsiveness of gut-associated lymphoid tissue (Ruggiero 2009). Eicosanoids, noted mediators of inflammation, are generated from polyunsaturated fatty acids (PUFA) stored as membrane phospholipids (Calder 2006, Ruggiero 2009). Derivatives of n-6 (omega-6) PUFAs act as pro-inflammatory mediators, while N-3 (omega-3) PUFAs found in fish oil, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), elicit antiinflammatory effects (Fetterman 2009, Yates 2014). DHA and EPA decrease membrane percent composition of n-6 PUFAs as well as inhibit metabolism of their derivatives, resulting in an alternate series of much less potent eicosanoids (Cabré 2012, Yates 2014). Other effects include decreased activation of NF-κβ, and decreased production of inflammatory cytokines such as TNF-α and IL-1β, known to play a major role in the pathological inflammation associated with IBD (Cabrè 2012, Fetterman 2009, Yates 2014). N-3 PUFAs also lead to the production of pro-resolving mediators such as resolvins and protectins which stimulate and activate endogenous pathways thereby terminating inflammation by reducing TNF-α and INF-γ secretion (Serhan 2008).

N-3 PUFAs have been implicated as an intervention for IBD for decades due to their anti-inflammatory properties (Calviello 2013, Ferguson 2010). Despite the vast number of promising preclinical animal studies, as well as human RCTs indicating benefit with minimal side effects, there is a consistent inability to reach statistical significance (Calviello 2013, MacLean 2005).

The results of the most recent systematic review are summarized in Table 1. Some sources of heterogeneity include differences in dose, source, placebo selection, and inconsistent reporting on a variety of outcomes (Cabré 2012, MacLean 2005). The lack of evaluation of patient-related factors such as baseline consumption of PUFAs among other confounders, as well as underpowered sample sizes, may further explain the failure to reach significance (Balk 2007, Cabré 2012). As a result, no optimal dose or formulation has been ascertained to date (Cabré 2012, Ferguson 2010). In summary, more well-designed studies which take into account pertinent patient- and treatmentspecific variables may be better able to replicate similar positive results in human studies.

Probiotics Probiotics are microorganisms that confer a health benefit to the host (Fedorak 2012). The use of VSL#3 and Escherichia Coli Nissle 1917 (EcN) will be examined due to the existence of substantial evidence supporting their role in the management of UC. VSL#3 is a high-concentration probiotic preparation including eight various bacterial species (Sung 2013). VSL#3 has been shown to improve epithelial barrier function through

up regulating anti-inflammatory cytokine pathways, specifically IL-10, as well as reduce the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and INF-γ (Fedorak 2012, Ng 2010, Sood 2009).

EcN is a well-characterized bacterial strain utilized as a probiotic drug (Sung 2013). EcN has an anti-inflammatory effect linked to the production of antimicrobial peptides. For example, EcN has been shown to induce human beta-defensin-2 (hBD-2 peptide) in human enterocytes in vitro. Antimicrobial peptides such as hBD-2 play a key role in enhancing the mucosal barrier to luminal bacteria (Wehkamp 2004). Moreover, EcN modulates expression of intestinal antimicrobial mechanisms by ultimately resulting in the secretion of IL-8, an antimicrobial cytokine.

Thus, EcN facilitates the phagocytosis of pathogenic microbes (Lammers 2002, Trebichavsky 2010).

VSL#3 has been shown to be superior to placebo in reducing the disease activity of mild-to-moderate UC. Specifically, significantly more patients exhibited an improvement in their UC disease activity index (DAI) score of at least 50%, which includes rectal bleeding, compared to those who received placebo (Tursi 2010). Another study reported a statistically significant dose response for rectally administered EcN enema with 40mL resulting in clinical remission, defined as a DAI less than or equal to 2 (Matthes 2010). Further well-designed studies, however, are still warranted to support the promising results found for the use of VSL#3 in active UC in addition to the use of EcN in the management of inactive UC (Jonkers 2012).

Vitamin D The main source of vitamin D is endogenous production in the skin upon exposure to ultraviolet radiation (Mouli 2014).

It has been demonstrated that the prevalence of IBD increases as one ventures further from the equator (Maitreyi 2011), suggesting that low levels of vitamin D may contribute to disease pathogenesis and severity (Joseph 2009). The functions of vitamin D most central to IBD include tissue barrier formation and immune regulation (Kong 2013). When vitamin D is present in sufficient amounts, it promotes the expression of cell adhesion proteins, stabilizing tight junctions between epithelial cells in the gut (Kong 2013). Since mucosal barrier function is disrupted in IBD, this mechanism is important to ensure mucosal barrier homeostasis (Friedman 2012, Kong 2013). Vitamin D also has an important role in the immune system (Mouli 2014). Upon activation of toll-like receptors on macrophages, vitamin D is converted to the active 1,25-dihydroxyvitamin D3, leading to upregulation of vitamin D receptor (VDR) expression. VDR activation inhibits production of proinflammatory cytokines such as IL-6 and TNF-α ameliorating the disease (Mouli 2014).

Few studies have been performed in humans to assess the effect of vitamin D on IBD pathogenesis and severity. Table 1 illustrates interventional human studies examining the effects of vitamin D supplements on disease activity in CD. The findings suggest that vitamin D supplementation lowers relapse rates and improves Crohn’s DAI scores in patients with CD (Mouli 2014). However, the lack of studies testing the efficacy of vitamin October 2014 | www.ihpmagazine.com

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D in UC, and the lack of a control group in some of the trials warrants further investigation (Mouli 2014). Patients with IBD should be screened for deficiencies in vitamin D before treatment is administered, thereby tailoring supplementation of vitamin D to individual patientsâ&#x20AC;&#x2122; needs (Mouli 2014).

Conclusion With the common belief that CAM therapies are safer than conventional therapies, many patients with IBD are turning to integrative interventions to alleviate clinical symptoms and maintain remission. This review analyzed the beneficial effects of alternative therapies in the management of UC and CD. Exploring the mechanism of alternative therapies for IBD provides evidence for therapeutic benefits, since these treatments exert their effects in a similar manner to conventional therapies. The high non-responder rate associated with conventional therapies, warranted the examination of CAM

therapies as a safe treatment for IBD. Curcuma longa, when administered in conjunction with 5-ASA, has been shown to improve symptoms and decrease relapse rates. Vitamin D supplementation has been shown to be clinically effective in patients with CD, however further research is warranted in UC. The probiotics VSL#3 and EcN, have shown promising results in both inactive and active UC to relieve symptoms such as rectal bleeding but have not shown to be effective in CD. A. paniculata extract and B. serrata extract have both shown benefits compared to placebo controls in the management of symptoms and maintenance of remission but failed to reach statistical significance. Likewise, studies investigating the use of fish oil consistently report nonsignificant results, possibly due to vast heterogeneity across studies. Due to the lack of extensive research with sufficient patient sample size, further research is warranted for these aforementioned CAM therapies. â&#x2013;

Table 1. Clinical trials.

Reference

Intervention

Dose

Subjects (n)

Findings

Sandborn 2010

HMPL-004 (A Paniculata extract)

Randomized, double blind, placebo controlled (8 weeks)

1200 mg daily

Moderately active CD (n=101)

Remission rate (CDAI < 150): HMPL-004 29.4%, placebo 14% (p=0.069)

Sandborn 2013

HMPL-004 (A Paniculata extract)

Randomized, double blind, placebo controlled (8 weeks)

1200mg or 1800mg daily

Mild-moderate UC (n=224)

Clinical response: HMPL-004 52%, placebo 40% (p=0.092) Clinical remission: HMPL-004 36%, placebo 25% (p=0.1173)

Tang 2010

HMPL-004 (A Paniculata extract)

Randomized, double blind vs 500mg mesalazine (8 weeks)

1200 mg daily

Mild-moderate UC (n=120)

Remission rate: HMPL-004 21%, mesalazine 16% (p>0.05) Adverse event: HMPL-004 13%, mesalazine 27%

Gupta 1997

Boswellia serrata gum resin extract (BSE)

Controlled trial vs 3g sulfasalazine 1050 mg daily (6 weeks)

Mild-moderate UC (n=30)

Remission rate: BSE 82%, sulfasalazine 75% (p>0.05)

Madisch 2007

Boswellia serrata gum resin extract (BSE)

Randomized, double blind, placebo controlled (6 weeks)

1200mg daily

Collagenous colitis (n=31)

Remission rate: BSE 63.6%, placebo 26.7% (p=0.04)

Holtmeier 2011

Boswellia serrata extract (Boswelan)

Randomized, double blind, placebo controlled (52 weeks)

2400mg daily

Inactive CD (n=82)

Maintenance of remission: Boswelan 59.9%, placebo 55.3% (p=0.85)

Curcuma Longa (Turmeric)

Pilot study (2 months)

550mg twice daily for 1 month and then 550mg three times daily another month

5 patients with UC and CD

9/10 IBD patients returned to the normalized levels of inflammatory indicator and other serologic indexes of inflammation

Curcuma Longa (Turmeric)

Randomized, multicenter, double blind, placebo control trial

45 patients received 1 g of curcumin twice daily while controls received a placebo

89 patients with quiescent UC

Clinical activity index and endoscopic index reduced in treatment group (P= 0.049) Relapse rate lower in treatment group (4.65%) compared to placebo (20.51%) (p= 0.04)

Holt 2005

Hanai 2006

68

Trial Design (study length)

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The Journal of IHP

CabrĂŠ 2012

Fish Oil (n-3 PUFAs)

Systematic review of 19 RCTs; 7 for active UC; 4 for inactive UC; 2 for active CD; 6 for inactive CD (Range: 6-24 months)

Both active and inactive UC and CD

Active UC: 3/7 statistically significant improvement in clinical score, 3/7 non-significant results, 1/7 endoscopic improvement with clinical symptomatic worsening.

Inactive UC, active CD, and inactive CD: All non-significant or inconclusive results

Miheller 2009

Vitamin D (active vs inactive VD)

Open label (6 weeks)

0.5 mcg daily

Inactive CD (n=37)

Active VD: CDAI decrease from 69 to 57 (p< 0.05) Inactive VD: No difference

Randomized, double blind, placebo controlled (12 months)

Vitamin D3

1200 IU Vitamin D3 daily

CD patients in clinical remission (n=104)

Relapse rate lower with VD3 (13%) compared to placebo (29%) (p= 0.06)

Vitamin D3

Open label (24 weeks)

Started at 1000 IU daily. Increased until serum reached 40 ng/ mL.

Mild to moderate CD (n=18).

CDAI scores decrease from 230 to 118 (p< 0.0001). Improved HRQOL.

Sood 2009

VSL#3

Multicenter, randomized, doubleblind, placebocontrolled trial (12 weeks)

3.6 x 10^12 CFU twice daily

Mild to moderately active UC (n=147)

> 50% improved disease activity at wk 6 in 32.5% vs 10% of patients (p = 0.001)

Tursi 2010

VSL#3

Randomized, placebo-controlled trial (8 weeks)

3.6 x 10^12 CFU daily

Mild to moderately active UC (n=144)

Improvement in UCDAI score in treatment (41[63.1%]) vs. control (29[40.8%]) groups (P<0.05)

VSL#3

Meta-analysis of randomized controlled trials

Jorgenses 2010

Yang 2013

Shen 2014

Matthes 2010

Escherichia Coli Nissle 1917 (EcN)

Randomized, placebo controlled trial (8 weeks)

EPA dose range : 1.2-5.1g; DHA dose range: 0.6-2.4g; or unclear

Remission rate higher with VSL #3 compared to placebo (P= 0.004).

No difference between treatment and control group with adverse events (P=0.94).

Escherichia Coli 1917 enema (4 x 10^9) vs (2X10^9) vs (10^9) daily vs Placebo

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Remission rates dose-dependent and statistically significant. EcN 40 ml (9/17 [52.9%]), 20 ml (8/18 [44.4%]), 10 ml (3/11 [27.3%]), and placebo (2/11 [18.2%]).

3

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Ruggiero C, Lattanzio F, Lauretani F, Gasperini B, Andres-Lacueva C, Cherubini A. Omega-3 polyunsaturated fatty acids and immune-mediated diseases: inflammatory bowel disease and rheumatoid arthritis. Curr Pharm Des. 2009;15(36):4135-48

Langmead L, Rampton DS. Review article: complementary and alternative therapies for inflammatory bowel disease. Aliment Pharmacol Ther. 2006; 23(3):341-349.

Sandborn W, Targan S, Byers V, Tang T. Randomized, double-blind, placebo-controlled trials of Andrographis paniculata extract (HMPL-004) in patients with moderately active Crohn’s Disease. Am J Gastroenterol 2010;105:s429-430

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Sandborn WJ, Targan SR, Byers VS, et al. Andrographis paniculata extract (HMPL-004) for active ulcerative colitis. Am J Gastroenterol 2013;108:90-98 Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol. 2008 May;8(5):349-61.

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Sood A, Midha V, Makharia GK, Ahuja V, Singal D, Goswami P, Tandon RK. The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol.

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References: Begum AN et al. J Pharmacol Exp Ther. 2008 Jul;326(1):196-208.

Belkacemi A et al. Expet Rev Mol Med. 2011 Nov; 13(e34):1-15.

Bisht S et al. Lab Invest. 2011 Sep;91(9):1383-95.

Buhrmann C et al. J Biol Chem. 2011 Aug 12;286(32):28556-66.

Cheng AL et al. Anticancer Res. 2001 Jul-Aug;21(4B):2895-900.

Dadhaniya P et al. Food Chem Toxicol. 2011 Aug;49(8):1834-42.

DiSilvestro RA et al. Nutr J. 2012 Sep 26;11:79.

Frautschy, SA. 38th Annual Meeting of the Society of Neuroscience, Washington DC, November 15, 2008.

Frautschy, SA et al. 39th Annual Meeting of the Society of Neuroscience , Chicago, IL October 2009.

Frautschy, SA et al. 39th Annual Meeting of the Society of Neuroscience , Chicago, IL October 2009.

Gandapu U et al. PLoS One. 2011 6(8):e23388.

Gota VS et al. J Agric Food Chem. 2010 Feb 24;58(4):2095-9.

Lao CD et al. BMC Complement Altern Med. 2006 Mar 17;6:10.

Mito S et al. Biol Pharm Bull. 2011 34(7):974-9.

Xie L et al. Int Immunopharmacol. 2011 Mar;11(3):323-30.

Yekollu SK et al. Diabetes. 2011 Nov;60(11):2928-38.

successful completion of the questions at the end of this paper has been approved for continuing education by the bddt-n; 1 credit pharmacology and by the cnpbc; one ce hour.

Metformin

Can a diabetes drug fight cancer?

By Maria Shapoval, ND and Heidi Fritz, MA, ND Maria Shapoval, ND Integrated Healthcare Centre 1255 Sheppard Ave E Toronto, Ontario M2K 1E2 mshapoval@ccnm.edu Heidi Fritz, MA, ND Bolton Naturopathic Clinic 64 King St W, Bolton, Ontario, L7E1C7 info@boltonnaturopathic.ca 74

Abstract This article reviews the novel, anticancer activity of a prescription medication, metformin (1,1-dimethylbiguanide). Metformin is best known as a diabetes medication; it is commonly used as the first-line medication for type 2 diabetes, as well as conditions of prediabetes, such as polycystic ovary syndrome (PCOS). There is increasing interest in metformin in the treatment and prevention of cancer, including among naturopathic physicians specializing in oncology. In this article, we will review initial research that raised awareness in this area, followed by proposed mechanisms that may explain proposed anticancer effects, and lastly, we will review the current clinical data in this area, based on human clinical trials.

www.ihpmagazine.com | October 2014

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

Introduction

Diabetes and Cancer Risk

Metformin is first and foremost an antihyperglycemic and insulin sensitizer (Violett 2012). This means that it improves the action of insulin and regulates high blood glucose levels (also known as blood sugar) in the body. As such, metformin is a first-line therapy for type 2 diabetes. In type 2 diabetes, there is loss of sensitivity to the effects of insulin, the hormone responsible for regulating blood glucose. Under normal conditions, insulin is secreted by the pancreas in response to an increase in blood glucose, such as after a meal. Insulin circulates in the blood and binds to insulin receptors on the surface of cells.

Activation of the insulin receptor signals a cascade of events that results in the cell moving more glucose receptors, called GLUT-4, to the cell surface, in order to take up glucose from the blood. The end result is a lowering of blood glucose levels to normal and intracellular storage of glucose, as glycogen or as fat.

In patients with type 2 diabetes, or in patients with prediabetes including polycystic ovary syndrome, the insulin receptor on the cell surface stops responding properly to insulin.

This results in the body producing more insulin, increasing blood insulin levels, in order to produce a stronger signal. This is important, because elevated insulin levels can contribute to worsening hormone balance in other areas, such as polycystic ovary syndrome (PCOS), and may be important in the development of cancer.

In the early stages of prediabetes, this may be enough to overcome reduced insulin sensitivity, returning blood glucose levels to within normal; with progression to diabetes, this ceases to be sufficient, and enough insulin can no longer be produced in order to overcome insulin receptor dysfunction. At this point, metformin may be prescribed.

Metformin acts by decreasing blood glucose levels through effects on the liver, including targeting the liver enzyme AMPactivated protein kinase (AMPK), and by indirectly increasing the responsiveness of the insulin receptor (Viollet 2012). Metformin decreases liver production of glucose (hepatic gluconeogenesis), and has positive effects on insulin receptor expression (Viollet 2012, Yuan 2003). In general, metformin has a good safety profile, with the most commonly reported side effects being digestive upset and depletion of vitamin B12 levels (Singh 2013).

The association of cancer with diabetes is a well-documented phenomenon. Patients with diabetes have increased risk of developing cancer.

For instance, a Japanese study of over 30,000 participants found that among participants with diabetes there was a modest increase in risk of cancer (Nakamura 2013). There was a nonsignificant increased total cancer risk (9%), among men with diabetes. Among women with diabetes, there was a significant 35% increased risk of cancer. This was also significant for sitespecific cancers, including liver cancer, bile duct cancer, stomach cancer, and laryngeal cancer.

However, given that information around the use of antidiabetic medication was not collected, the impact of diabetes may in fact be higher.

Another study found that there was increased risk of cancer among diabetic patients medicated with non-metformin diabetes drugs (Bowker 2006). The study included over 10,000 patients who were new users of various diabetes drugs.

After only 5.4 years of follow-up, there was already a significantly higher risk of developing cancer among patients treated with the drug class sulfonylureas, and a significantly increased risk of dying from cancer among patients treated with insulin, compared to patients treated with metformin. It is unclear whether these observations reflect harmful effects of sulfonylureas and insulin, or whether this reflects risk reduction by metformin.

Other data have identified the presence of diabetes as a risk factor for colorectal cancer (Tseng 2012), lung cancer (Luo 2012), and breast cancer (Bordeleau 2011).

The presence of diabetes has also been linked to worse outcomes in cancer treatment. For instance, in a study of prostate cancer patients who had surgical treatment (radical prostatectomy), obese men with diabetes had four-fold increased risk of metastasis (distant spread of the cancer), despite having more aggressive anticancer treatments (Wu 2013). In another study, diabetes at the time of diagnosis independently predicted death from colorectal cancer (van de Poll-Franse 2012).

What has emerged more recently is that patients with diabetes who take metformin may have a reduced risk of developing cancer compared to their â&#x20AC;&#x153;peers,â&#x20AC;? patients with similar characteristics including a diagnosis of diabetes, but who have not been treated with metformin.

The mechanism for this effect is actively under study.

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Mechanism Lab-based studies indicating that Metf may possess anticancer activity began emerging almost a decade ago (Dowling 2007, Sahra 2008, Zakikhani 2006). These studies indicate that metformin inhibits cancer cell growth through the activation of AMPK. Activated AMPK promotes the activity on insulin receptor and insulin receptor substrate (IRS-2), thus increasing insulin sensitivity, resulting in increase in translocation of GLUT-1 and subsequent inhibition of gluconeogenesis (Li 2012, Pernicova 2014). By reducing hyperglycemia, metformin addresses hyperinsulinemia, which is associated with increased androgens and estrogen due to insulinâ&#x20AC;&#x2122;s inhibitory action on sex-hormone binding globulin (SHBG) synthase and subsequent poor prognosis of several hormone dependent cancers (Campagnoli 2013, Pernicova 2014) Additionally AMPK inhibits the rapamycin (mTOR) pathway, resulting in a decrease in protein expression and synthesis and tumor cell proliferation (Dowling 2007, Higurashi 2012, Zakikhani 2006).

Other mechanisms include reduction of fatty acid synthase

(decreased mitotic activity), inhibition of insulin-growth factor (IGF-1), which further inhibits mTOR signaling, as well as reduction in reactive oxygen species production and associated DNA damage by the inhibition of mitochondrial respiratory complex 1 by metformin. Direct inhibition of cancer stem cells has been demonstrated by Hirsch et al (2009), but the apoptotic effect of metformin continues to be debated (Janjetovic 2011, Pernivoca 2014, Sahra 2008). Together, this data combined with metforminâ&#x20AC;&#x2122;s effect on the mTOR pathway suggest that this drug may be useful even in nondiabetic patients. This is especially relevant given the large number of individuals who may have insulin resistance (prediabetes), hence increased insulin levels, but do not yet meet diagnostic criteria for diabetes.

Metformin and Cancer Risk The first data on the anticancer effects of metformin came from a 2005 study in the British Medical Journal. This study analyzed a cohort of over 11,000 Scottish patients who had been diagnosed with type 2 diabetes (Evans 2005). Among patients with diabetes who were treated with metformin,

Ref.

Design

Population

Cancer

Outcome

Mei 2014

6 retrospective cohort studies

23,255 patients with diabetes

Colorectal cancer

HR 0.56; 95% CI, 0.41-0.77 *report potential risk of publication bias*

Wang 2014

10 cohort, 3 case-control

Patients with diabetes

Pancreatic cancer

RR 0.63; 95% CI 0.460.86; p=0.003 *significant heterogeneity in studies; 5 report sig risk reduction, while 8 report NS*

Col 2012

4 cohort, 2 case-control

Patients with diabetes

Breast cancer

OR 0.83; 95% CI 0.710.97; p=0.06

Zhang 2012

2 case control, 3 prospective cohort

105,495 patients with diabetes

Liver cancer

OR 0.38; 95% CI 0.240.59; p<0.001

Zhang 2011

2 case control, 3 retrospective cohort

108, 161 patients with diabetes

Colorectal cancer

RR 0.63; 95% CI 0.500.79; p<0.001

Table 1: Summary of systematic reviews with meta-analyses Several systematic reviews and meta-analyses of observation studies have since attempted to investigate the degree of protection offered by metformin across different types of cancers. Significant risk reduction has been observed in pancreatic (RR 0.63; 95% CI 0.46-0.86, p=0.003; Wang 2014), colorectal (RR 0.68; 95% CI 0.53-0.88, p=0.003; Mei 2014, Noto 2012, Zhang 2011), liver (RR 0.20; 95% CI 0.07-0.59; p<0.001; Noto 2012, Zhang 2012), breast (RR 0.83; 95% CI 0.71-0.97; Col 2012), endometrial and ovarian cancers (Zhang 2014). While controversial or non-statistically significant results were found for prostate, lung and bladder cancers (Noto 2012, Zhang 2014).

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

Another study found that there was increased risk of cancer among diabetic patients medicated with non-metformin diabetes drugs.

there was a lower risk of cancer compared to diabetic patients who were not treated with metformin, adjusted odds ratio, 0.77 (95% confidence interval 0.64â&#x20AC;&#x201C;0.92). This indicates a 23% reduction in cancer risk associated with use of metformin. Interestingly, there was also a dose-response curve, indicating that patients who received a higher dose of metformin had a parallel decrease in risk.

Another study found that cumulative duration of metformin use following a diagnosis of prostate cancer was associated with decreases in both all-cause death as well as prostate cancer death (Margel 2013). Similarly, in colorectal cancer patients with diabetes, high-dose metformin use was associated with a significant reduction in death from colorectal cancer, by over 50%, compared to diabetics not treated with metformin (Spillane 2013). Another study has shown that having diabetes and not taking metformin was associated with worse cancer outcomes in patients with urothelial carcinoma compared to patients who had diabetes and took metformin, as well as nondiabetic patients (Rieken 2014). In diabetic women with breast cancer, use of metformin has been shown to increase survival (Peeters 2013).

Metformin as a form of Chemotherapy?

There is a small amount of data available so far from clinical trials. One RCT evaluated the effect of metformin (850mg tid for 4 weeks) on Ki-67, a marker of tumor proliferation, in 200 nondiabetic women about to undergo surgery for breast cancer compared to placebo (Bonanni 2012). This study found no significant effects overall; however, when looking at those women with insulin resistance, there was a nonsignificant but notable10% decrease in Ki-67. There was also a nonsignificant 11%

increase in women with good insulin sensitivity.

Kalinsky et al (2014) conducted a study with 35 non-diabetic women with breast cancer 2 weeks before surgery and found similar non statistical changes in Ki67 (1500mg qd metformin).

Another pilot study of breast cancer found that there was a significant decrease in Ki-67 associated with use of metformin 1000 mg per day before surgery (Hadad 2011). Women were randomized to treatment with metformin and took metformin for two weeks prior to having a biopsy. After taking metformin, the Ki-67 proliferative index of the tumor tissue was significantly (p=0.027 compared to baseline) lower in patients who took metformin (NS results in placebo group). Notably, these women did not have diabetes. Similar effects were found in another pilot study (Niraula 2012).

A meta-analysis of 11 randomized-control trials (>500 participants, â&#x2030;Ľ 1 yr follow up) yielded a RR of 0.94 (95% CI 0.79, 1.12) for all-cause mortality (Stevens 2012). Authors conclude that although the results of the metaanalysis do not demonstrate a statistical benefit, given the short follow up length (< 5yo) and the large heterogeneity in the studies, in terms of comparators used (placebo, usual care, other antidiabetic medications), the RCTs may not be adequately reflecting the long-term effects of metformin.

Metformin Combined with Chemotherapy Several studies examined the potential for synergistic action of metformin in combination with chemotherapeutic agents. An in vitro study compared the action of 5-fluorouracil (5-FU) alone on colorectal cancer (CRC) cells, as well as cancer stem cells (CD133+ CSCS), and in combination with metformin. The combination resulted in a statically significant increase in October 2014 | www.ihpmagazine.com

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In diabetic women with breast cancer, use of metformin has been shown to increase survival. apoptosis of the CRC cells (p=0.029) as well as inhibition of the CD133+ cells (p=0.027. Similar results were reported by Honjo et al (2014) in the case of esophageal cancer. Another in vitro study reports independent apoptotic activity of metformin, as well as an almost 3 times increased apoptotic activity of gefitinib when combined with metformin (p<0.001) in the case of non-small cell lung cancer (NSCLC).

A small (n=20) phase 1 clinical trial compared the combinations of chemotherapeutic drug exemestane (25mg qd) with metformin (1500mg qd) alone or in addition to rosiglitazone (6mg qd), another antidiabetic drug (Esteva 2013) on breast cancer in postmenopausal women. The triple therapy was suspended a few times due to the severity of diarrhea.

No other additional side effects were observed, relating to the antidiabetic therapy, and the therapies were reported to be well tolerated. A phase 3 clinical trial is underway to determine the efficacy of these combinations.

Current Trials A randomized, double-blind, placebo-controlled trial that is currently in progress is evaluating the ability of metformin to References: Bonanni B, Puntoni M, Cazzaniga M, Pruneri G, Serrano D, GuerrieriGonzaga A, Gennari A, Trabacca MS, Galimberti V, Veronesi P, Johansson H, Aristarco V, Bassi F, Luini A, Lazzeroni M, Varricchio C, Viale G, Bruzzi P, Decensi A. Dual effect of metformin on breast cancer proliferation in a randomized presurgical trial. J Clin Oncol. 2012 Jul 20;30(21):2593-600.

Bordeleau L, Lipscombe L, Lubinski J, Ghadirian P, Foulkes WD, Neuhausen S, Ainsworth P, Pollak M, Sun P, Narod SA; Hereditary Breast Cancer Clinical Study Group. Diabetes and breast cancer among women with BRCA1 and BRCA2 mutations. Cancer. 2011 May 1;117(9):1812-8.

Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin.

Diabetes Care. 2006 Feb;29(2):254-8.

Campagnoli C, Pasanisi P, Abbà C, Ambroggio S, Biglia N, Brucato T, Colombero R, Danese S, Donadio M, Venturelli E, Zito G, Berrino F. Effect of different doses of metformin on serum testosterone and insulin in nondiabetic women with breast cancer: a randomized study. Clin Breast Cancer.

2012 Jun;12(3):175-82.

Campagnoli C, Berrino F, Venturelli E, Abbà C, Biglia N, Brucato T, Cogliati P, Danese S, Donadio M, Zito G, Pasanisi P. Metformin decreases circulating androgen and estrogen levels in nondiabetic women with breast cancer. Clin Breast Cancer. 2013 Dec;13(6):433-8.

Col NF, Ochs L, Springmann V, Aragaki AK, Chlebowski RT. Metformin and breast cancer risk: a meta-analysis and critical literature review. Breast Cancer Res Treat. 2012 Oct; 135(3): 639-46

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prevent precancerous colorectal polyps in nondiabetic patients (Higurashi 2012). A previous pilot study by the same team conducted among 26 nondiabetic patients with rectal aberrant crypt foci (ACF), a precancerous lesion of the colon (Hosono 2010). Patients were randomized to treatment with 250 mg per day of metformin or placebo. After one month, the metformin group had a significant decrease in the mean number of ACF per patient, whereas this did not change in the control group. In addition, the proliferating cell nuclear antigen index, a measure of cellular proliferation, was significantly decreased in normal colon tissue of the metformin-treated patients.

Conclusion Data on the effect of metformin on risk of cancer or cancer treatment are largely based on observational data; there are a large number of trials currently underway to assess the anticancer effects in randomized, controlled trials (Pernicova 2014). A question that has yet to be answered by further research is whether the anticancer effects of metformin among patients with diabetes will hold equally true among patients who do not have diabetes. ■

Dowling RJ, Zakikhani M, Fantus IG, Pollak M, Sonenberg N. Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancercells. Cancer Res. 2007 Nov 15;67(22):10804-12.

Esteva FJ, Moulder SL, Gonzalez-Angulo AM, Ensor J, Murray JL, Green MC, Koenig KB, Lee MH, Hortobagyi GN, Yeung SC. Phase 1 trial of exemestane in combination with metformin and rosiglitazone in non-diabetic obese postmenopausal women with hormone receptor-positive metastatic breast cancer. Cancer Chemother Pharmacol. 2013 Jan; 71(1): 63-72 Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005 Jun 4;330(7503):1304-5.

Goodwin PJ, Pritchard KI, Ennis M, Clemons M, Graham M, Fantus IG. Insulin-lowering effects of metformin in women with early breast cancer. Clin Breast Cancer. 2008 Dec;8(6):501-5.

Hadad S, Iwamoto T, Jordan L, Purdie C, Bray S, Baker L, Jellema G, Deharo S, Hardie DG, Pusztai L, Moulder-Thompson S, Dewar JA, Thompson AM. Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial. Breast Cancer Res Treat. 2011Aug;128(3):783-94.

Higurashi T, Takahashi H, Endo H, Hosono K, Yamada E, Ohkubo H, Sakai E, Uchiyama T, Hata Y, Fujisawa N, Uchiyama S, Ezuka A, Nagase H, Kessoku T, Matsuhashi N, Yamanaka S, Inayama Y, Morita S, Nakajima A. Metformin efficacy and safety for colorectal polyps: a double-blind randomized controlled trial. BMC Cancer. 2012 Mar 26;12:118.

The Journal of IHP â&#x20AC;&#x201C; Continuing Education Honjo S, Ajani JA, Scott AW, Chen Q, Skinner HF, Stroehlein J, Johnson RL, Song S. Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR pathway in esophageal cancer. Int J Oncol. 2014 May 21.

Hosono K, Endo H, Takahashi H, Sugiyama M, Sakai E, Uchiyama T, Suzuki K, Iida H, Sakamoto Y, Yoneda K, Koide T, Tokoro C, Abe Y, Inamori M, Nakagama H, Nakajima A. Metformin suppresses colorectal aberrant crypt foci in a short-term clinical trial. Cancer Prev Res (Phila). 2010 Sep;3(9):1077-83.

Janjetovic K, Vucicevic L, Misirkic M, Vilimanovich U, Tovilovic G, Zogovic N, Nikolic Z, Jovanovic S, Bumbasirevic V, Trajkovic V, Harhaji-Trajkovic L. Metformin reduces cisplatin-mediated apoptotic death of cancer cells through AMPK-independent activation of Akt. Eur J Pharmacol. 2011 Jan 25;651(1-3):41-50.

Luo J, Chlebowski R, Wactawski-Wende J, Schlecht NF, Tinker L, Margolis KL. Diabetes and lung cancer among postmenopausal women. Diabetes Care. 2012 Jul;35(7):1485-91.

Ma J, Guo Y, Chen S, Zhong C, Xue Y, Zhang Y, Lai X, Wei Y, Yu S, Zhang J, Liu W. Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma. BMC Cancer. 2014 Mar 11;14:172.

Margel D, Urbach DR, Lipscombe LL, Bell CM, Kulkarni G, Austin PC, Fleshner N. Metformin use and all-cause and prostate cancerspecific mortality among men with diabetes. J Clin Oncol. 2013 Sep 1;31(25):3069-75.

Morgillo F, Sasso FC, Della Corte CM, Vitagliano D, Dâ&#x20AC;&#x2122;Aiuto E, Troiani T, Martinelli E, De Vita F, Orditura M, De Palma R, Ciardiello F. Synergistic effects of metformin treatment in combination with gefitinib, a selective EGFR tyrosine kinase inhibitor, in LKB1 wilde-type NSCLC cell lines. Clin Cancer Res. 2013 Jul; 19(13): 3508-19 Mei ZB, Zhang ZJ, Liu CY, Cui A, Liang ZL, Wang GH, Cui L. Survival benefits of metformin for colorectal cancer patients with diabetes: a systematic review and meta-analysis. PLoS One. 2014 Mar 19;9(3):e91818 Nakamura K, Wada K, Tamai Y, Tsuji M, Kawachi T, Hori A, Takeyama N, Tanabashi S, Matsushita S, Tokimitsu N, Nagata C. Diabetes mellitus and risk of cancer in Takayama: a population-based prospective cohort study in Japan. Cancer Sci. 2013 Oct;104(10):1362-7.

Niraula S, Dowling RJ, Ennis M, Chang MC, Done SJ, Hood N, Escallon J, Leong WL, McCready DR, Reedijk M, Stambolic V, Goodwin PJ. Metformin in early breast cancer: a prospective window of opportunity neoadjuvant study. Breast Cancer Res Treat. 2012 Oct;135(3):821-30.

Noto H, Goto A, Tsujimoto T, Noda M. Cancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis. PLoS One. 2012; 7(3): e33411 Peeters PJ, Bazelier MT, Vestergaard P, Leufkens HG, Schmidt MK, de Vries F, De Bruin ML. Use of metformin and survival of diabetic women with breast cancer. Curr Drug Saf. 2013 Nov;8(5):357-63.

Pernicova I, Korbonits M. Metformin--mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol. 2014 Mar;10(3):143-56.

Rieken M, Xylinas E, Kluth L, Trinh QD, Lee RK, Fajkovic H, Novara G, Margulis V, Lotan Y, Martinez-Salamanca JI, Matsumoto K, Seitz C, Remzi M, Karakiewicz PI, Scherr DS, Briganti A, Kautzky-Willer A, Bachmann A, Shariat SF; UTUC Collaboration. Diabetes mellitus without metformin intake is associated with worse oncologic outcomes after radical

nephroureterectomy for upper tract urothelial carcinoma. Eur J Surg Oncol.

2014 Jan;40(1):113-20.

Ben Sahra I, Laurent K, Loubat A, Giorgetti-Peraldi S, Colosetti P, Auberger P, Tanti JF, Le Marchand-Brustel Y, Bost F. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene. 2008 Jun 5;27(25):3576-86.

Singh AK, Kumar A, Karmakar D, Jha RK. Association of B12 deficiency and clinical neuropathy with metformin use in type 2 diabetes patients. J Postgrad Med. 2013 Oct-Dec;59(4):253-7.

Spillane S, Bennett K, Sharp L, Barron TI. A cohort study of metformin exposure and survival in patients with stage I-III colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2013 Aug;22(8):1364-73.

Stevens RJ, Ali R, Bankhead CR, Bethel MA, Cairns BJ, Camisasca RP, Crowe FL, Farmer AJ, Harrison S, Hirst JA, Home P, Kahn SE, McLellan JH, Perera R, Pluddemann A, Ramachandran A, Roberts NW, Rose PW, Schweizer A, Viberti G, Holmann RR. Cancer outcomes and allcause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials. Diabetologia. 2012; 55: 2591-2603 Tseng CH. Diabetes, metformin use, and colon cancer: a population-based cohort study in Taiwan. Eur J Endocrinol. 2012 Sep;167(3):409-16. van de Poll-Franse LV, Haak HR, Coebergh JW, Janssen-Heijnen ML, Lemmens VE. Disease-specific mortality among stage I-III colorectal cancer patients with diabetes: a large population-based analysis. Diabetologia. 2012 Aug;55(8):2163-72.

Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond). 2012 Mar;122(6):253-70.

Wu C, Aronson WJ, Terris MK, Presti JC Jr, Kane CJ, Amling CL, Freedland SJ. Diabetes predicts metastasis after radical prostatectomy in obese men: results from the SEARCH database. BJU Int. 2013 Jun;111(8):E310-8.

Yuan L, Ziegler R, Hamann A. Metformin modulates insulin post-receptor signaling transduction in chronically insulin-treated Hep G2 cells. Acta Pharmacol Sin. 2003 Jan;24(1):55-60.

Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 2006 Nov 1;66(21):10269-73.

Zhang ZJ, Zheng Zj, Kan H, Song Y, Cui W, Zhao G, Kip KE. Reduced risk of colorectal cancer with metformin therapy in patients with type 2 diabetes: a meta-analysis. Diabetes Care. 2011 Oct; 34(10): 2323-8 Zhang ZJ, Zheng ZJ, Shi R, Su Q, Jiang Q, Kip KE. Metformin for liver cancer prevention in patients with type 2 diabetes: a systematic review and metaanalysis. J Clin Endocrinol Metab 2012; 97: 2347-53 Zhang Y, Guan M, Zheng Z, Zhang Q, Gao F, Xue Y. Effects of metformin on CD133+ colorectal cancer cells in diabetic patients. PLoS One. 2013 Nov; 8(11): e81264 Zhang ZJ, Li S. The prognostic value of metformin for cancer patients with concurrent diabetes: a systematic review and meta-analysis. Diabetes Obes.

Metab. 2014 Jan 27

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Questions

2. Which of the following correctly describes the activity of metformin? a) Activates liver AMP-activated protein kinase (AMPK) and increases insulin receptor sensitivity b) Increases translocation of GLUT-1 to cell membrane c) Inhibits mTOR signaling pathway d) All of the above

6. The potential anticancer effect of metformin was first documented in a large published in the British Medical Journal. In this study there was: a) 13% reduced odds of developing cancer among metformin-treated diabetics, compared with diabetics who were treated with other medications. b) 53% reduced odds of developing cancer among metformin-treated diabetics, compared with diabetics who were treated with other medications. c) 73% increased odds of developing cancer among insulin-treated diabetics, compare with diabetics who were non-insulin dependent. d) A dose response curve showing that those patients who received a higher dose of metformin demonstrated correspondingly lower rates of cancer.

3. Meformin may indirectly modulate hormones such as estrogen and testosterone by decreasing insulin-like growth factor-1 (IGF-1) and increasing sex hormone binding globulin (SHBG). a) True b) False

7. Metformin has been shown to improve cancer survival among which of the following: a) men with diabetes and prostate cancer b) patients with diabetes and colorectal cancer c) women with diabetes and breast cancer d) All of the above

4. The relationship between diabetes and risk of cancer was first documented in large observational studies. These showed: a) Patients with diabetes have increased risk of developing cancer, up to 35% in one study. b) There were site-specific effects for liver cancers, bile duct cancers, stomach cancer, as well as links with colorectal cancer, lung cancer, and breast cancer. c) The presence of diabetes was also associated with poorer treatment outcomes, particularly in patients with prostate cancer and colorectal cancer. d) All of the above.

8. With respect to use in non-diabetic patients, metformin has been shown to decrease Ki-67 index, a measure of cell proliferation, in women with breast cancer. a) True b) False

1. Which of the following is true about metformin? a) Metformin is used in the treatment of type 1 diabetes and polycystic ovary syndrome b) Metformin belongs to the biguanide class of hypoglycemic agents. c) Neuropathy is a common side effect of metformin d) All of the above.

5. Patients with diabetes who take metformin may have a reduced risk of developing cancer compared to their “peers,” that is, patients with similar characteristics including a diagnosis of diabetes, but who have not been treated with metformin. a) True b) False

9. Similar studies are underway examining whether metformin can decrease conversion of benign colon polyps to malignant lesions. Thus far, one study has shown that metformin treatment significantly decrease cell proliferation in the colon tissue of these patients. a) True b) False 10. Main side effects of metformin include depletion of vitamin B12 and digestive upset. a) True b) False

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GREENS+ ORIGINAL Greens + by Genuine Health is a nourishing superfood blend containing 23 plant-based ingredients such as lecithin, spirulina, barley grass, wheat grass, chlorella, eight strains of probiotics, and herbs such as Siberian ginseng and milk thistle to help support key areas such as stress management and liver function. As such, Greens+ is an ideal product for improving energy and vitality, balance pH, and providing antioxidants to support good health.

Greens+ formula has been the subject of extensive research, investigating its effect on a variety of endpoints including in vivo antioxidant capacity, pH and alkalinity, energy, osteoporosis, and cancer cell growth (Boon 2004, Rao 2008, Rao 2011). Research at the University of Toronto has shown that greens+ demonstrates potent antioxidant and cell protective effects in vitro and in vivo (Guthrie 2011, International Journal of Molecular Science, Rao 2011). The greens+ formula was found to contain key phytonutrients such as quercetin, apigenin, kaempferol, and luteolin. The formula was able to inhibit lipid peroxidation, which may present a role in chronic diseases including cardiovascular, neurological, and psychiatric illness. In a human clinical trial, subjects supplemented with greens+ for one month experienced significant increases in their in vivo antioxidant capacity, a reduction in oxidative cellular damage to fats and proteins, and an increase in the key antioxidant enzyme, glutathione peroxidase (Rao 2011). This study underscores the bioavailability of nutrients in this formula as well as its therapeutic effect in the human body. Interestingly, the ingredient lecithin may account for up to 12-15% of the total antioxidant capacity of the greens+ formula.

A randomized, double blind, placebo controlled trial conducted in over 100 subjects at the University of Toronto found that supplementation with greens+ was effective in increasing energy and vitality, with significant improvements compared to placebo (p=0.018) (Boon 2004). There were also trends toward improved mental health, well-being and overall health associated with use of greens+.

The greens+ formula has been demonstrated to influence bone metabolism (Rao 2008). In an in vitro study, exposure of osteoblast-like cells, SaOS-2 cells, to various concentrations of total free polyphenolic from greens+ extracts resulted in increased osteoblast number, and stimulated mineralized bone nodule formation (Rao 2008). These results indicate that greens+ may promote maturation of osetoprogenitors and exert beneficial effects on bone formation. Authors states, “we speculate that it may be a good alternative to drugs for the prevention of osteoporosis” (Rao 2008). A second mechanism of its effect on bone is modulation of the Potential Renal Acid Load (PRAL); PRAL analysis evaluates an agent’s potential for promoting acid or alkaline formation in vivo. In general, foods such as fruits and vegetables are alkaline forming, while meats and grains are acid forming. With chronic over-consumption of “acidic” foods, calcium is released from bone to buffer the acid produced (Remer 2011, Shi 2012) . Greens+ has been shown to promote an alkaline state, and may offsetting the negative effects of meat and grain consumption by reducing calcium release and helping preserve bone mass.

Greens+ Formula Ingredients per 8.5g Dose Lecithin (97% oil free; soybean; 26% 2171 phosphatidylcholine) Spirulina platensis (Spirulina cells) 1450 Malus domestica (Apple fruit) 1033 Hordeum vulgare (Organic barley grass) 734 Medicago sativa (Organic alfalfa grass) 383 Triticum aestivum (Organic wheat grass) 383 Chlorella pyrenoidosa (Japanese 383 chlorella) Glycine max (Organic soy sprouts) 383 Oryza sativa (Organic whole brown rice 383 kernel) Royal jelly standardized to 5% 10-HAD 150 Bee pollen 150 Glycyrrhiza uralensis (Licorice roots 116 standardized to 10% glycyrrhizin (5:1 = 580mg) Malpighia glabra (Acerola berry juice 115 standardized to 18% vitamin C) FOS (fructooligossacharides) (from 100 chicory root; [Cichorium intybus]) Eight bacterial cultures 100 Lactobacillus helveticus (R0052) 0.19 Lactobacillus rhamnosus (R0011) 0.43 Lactobacillus casei (R0215) 0.09 Lactobacillus plantarum (R1012) 0.09 Lactobacillus salivarius (R0078) 0.04 Bifidobacterium longum (R0175) 0.04 Bifidobacterium bifidum (R0071) 0.04 Bifidobacterium breve (R0070) 0.24 Eleutherococcus senticosus (Siberian 60 ginseng roote extract standardized to 0.8% eleutherosides (28:1 = 1680mg)) Silybum marianum L. (Milk thistle seed 60 extract standardized to 86% silymarin (40:1 = 2400mg)) Beta vulgaris (Organic red beet root) 43 Palmaria palmate (Atlantic dulse 33 seaweed) Ginkgo biloba L. leaf extract 20 standardized to 24% ginkgo flavonglycosides and 6% terpene lactones (50:1 = 1000mg) Camellia sinensis L. (Japanese green tea 15 leaf extract standardized to 90% polyphenols (20:1 = 300mg)) Vaccinium myrtillus L. (European 10 bilberry extract standardized to 25% anthocyanidins (100:1 = 1000mg)) Vitis vinifera (Grape extract standardized 5 to 95% proanthocyanidins and 200 ppm resveratrol (500:1 = 2500mg)) Non medicinal ingredients: stevia, skim milk

Unit mg mg mg mg mg mg mg mg mg mg mg mg mg mg mg bCFU bCFU bCFU bCFU bCFU bCFU bCFU bCFU mg mg mg mg mg

gm mg mg

Finally, greens+ also contains eight strains of Lactobacillus and Bifidobacertium probiotic species to ensure healthy digestion and immune function. These species have been shown to improve irritable bowel syndrome, reduce upper respiratory tract infections, and may have a role in maintaining healthy immune tolerance (Rerksuppaphol 2012, Yoon 2014).

Greens+ is one of the most thoroughly research nutraceutical blends of its kind, with confirmed benefits on several important areas of health demonstrated by laboratory studies and human clinical research.

Recommended use: To increase your energy and well-being.

Adult dosage: Mix 3 tsp (8.5g) in 1 cup (250mL) of pure water or juice. Shake well. If you are a new user of greens+, begin with 1 tsp daily and gradually increase to 3 tsp daily over a 3 week period. Do not take on empty stomach. Consult a health care practitioner for use beyond 3 months.

Caution: Not to be taken by children, during pregnancy, while breastfeeding, by those on medication or with chronic health problems unless under the recommendation of a health care practitioner. Consult a health care practitioner prior to use if you have nausea, fever, vomiting, bloody diarrhea or severe abdominal pain. Do not use if you have gastrointestinal blockage or 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 occur, persist or worsen beyond 3 days. Use with caution if allergic to bee products. Keep refrigerated after opening.

References Boon H, Clitheroe J, Forte T. Effects of greens+: a randomized, controlled trial. Can J Diet Pract Res. 2004 Summer;65(2):66-71.

Rao LG, Balachandran B, Rao AV. Polyphenol extract of Greens+™ nutritional supplement stimulates bone formation in cultures of human osteoblast-like SaOS-2 cells.

J Diet Suppl. 2008;5(3):264-82.

Rao V, Balachandran B, Shen H, Logan A, Rao L. In vitro and in vivo antioxidant properties of the plant-based supplement greens+™. Int J Mol Sci. 2011;12(8):4896-908.

Remer T, Manz F, Alexy U, Schoenau E, Wudy SA, Shi L. Long-term high urinary potential renal acid load and low nitrogen excretion predict reduced diaphyseal bone mass and bone size in children. J Clin Endocrinol Metab. 2011 Sep;96(9):2861-8.

Rerksuppaphol S, Rerksuppaphol L. Randomized controlled trial of probiotics to reduce common cold in schoolchildren. Pediatr Int. 2012 Oct;54(5):682-7.

Shi L, Libuda L, Schönau E, Frassetto L, Remer T. Long term higher urinary calcium excretion within the normal physiologic range predicts impaired bone status of the proximal radius in healthy children with higher potential renal acid load. Bone. 2012 May;50(5):1026-31.

Vaghef-Mehrabany E, Alipour B, Homayouni-Rad A, Sharif SK, Asghari-Jafarabadi M, Zavvari S. Probiotic supplementation improves inflammatory status in patients with rheumatoid arthritis. Nutrition. 2014 Apr;30(4):430-5.

Yoon JS, Sohn W, Lee OY, Lee SP, Lee KN, Jun DW, Lee HL, Yoon BC, Choi HS, Chung WS, Seo JG. Effect of multispecies probiotics on irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Gastroenterol Hepatol. 2014 Jan;29(1):52-9.

L-5-MTHF SAP PRODUCT MONOGRAPH

In recent years, there has been a substantial amount of research about folate metabolism, and it is now very apparent that a subset of the population is unable to metabolize folate efficiently.[1] The enzyme methylenetetrahydrofolate reductase (MTHFR) directs folate either to DNA synthesis or to homocysteine (Hcy) remethylation.[1] There is a common MTHFR C677T polymorphism which affects the activity of this enzyme, and hence folate distribution, in about 33% of the North American population, where about 10% of the population is homozygous for this mutation.[1] The impairment that this polymorphism results in is altered folate status. If the patient is homozygous, this has been regarded as harmful, because it is associated with a high concentration of homocysteine, increased risk of neural tube defects, and colorectal neoplasias, and may also predispose individuals to adverse effects from drugs with antifolate effects.[1, 2]

A total of 96 patients with dementia, who had scored between 12 and 23 on the Mini Mental State Examination and/or ≥ 18 on the Hamilton Depression Rating Scale (HDRS) were included in the study. After a 2-week placebo run-in, patients were divided into two groups and received either 5-MTHF at 50 mg/d or trazodone at 100 mg/d for eight weeks.[5] At the end of eight weeks, patients’ HDRS score in the 5-MTHF group reduced from 23 ± 3 to 18 ± 6, and in the trazodone group from 23 ± 3 to 19 ± 5.[5]

HOMOCYSTEINE AND VASCULAR DISEASE

An elevated total plasma homocysteine is a risk factor for vascular disease as well as adverse pregnancy outcomes. Excessive intake of folic acid, though, can mask an undiagnosed vitamin B12 deficiency.[6] The biologically active 5-MTHF may be a viable alternative to folic acid, because it is unlikely to mask vitamin B12 deficiency symptoms.[6] In a double-blind, randomized study, researchers looked at the outcome of supplementing either folic acid or 5-MTHF or placebo on tHcy levels.[6] A total of 144 female patients were divided into four groups and received 400 mcg folic acid, 416 mcg 5-MTHF, 208 mcg 5-MTHF, or placebo.[6] The concentration of tHcy and plasma folate was measured at baseline and at four-week intervals.[6] All three treatment groups saw a decrease in tHcy and did not differ significantly. The increase in plasma folate was significantly lower in the group receiving 208 mcg 5-MTHF.[6] Researchers concluded that 5-MTHF was an adequate alternative to folic acid for tHcy reductions and, for this purpose, 208 mcg and 416 mcg of 5-MTHF had similar efficacy.[6]

L-5-MTHF IN PREGNANCY

DEPRESSION

Sufficient levels of folate are critical for healthy brain and body functioning.

Folate is required in the brain for synthesis of norepinephrine, serotonin, and dopamine.[3] There is research supporting that folate deficiency may lead to an increased risk of depression, less than optimal outcomes with antidepressant treatment, as well as increased risk of cognitive impairment.[3] In North America, folic acid is fortified in several grain products; however, due to genetic polymorphisms absorption and utilization, it is not optimal for several people. [1] Supplementing with the active form of folate, 5-methyltetrahydrofolate (5-MTHF), may be effective in the prevention and treatment of both depression and dementia.[3] There are several different pharmaceutical agents available to treat major depressive disorder (MDD); despite this, many patients experience only mild to modest improvements and low remission rates.[4] A review article investigating the effect of folate and its efficacy in treating mood disorders discovered some favorable results:[4] researchers found that supplementing with various formulations of folates appears to be both well-tolerated and efficacious in reducing depression symptoms.[4] Researchers also mentioned that supplementing with the bioavailable form 5-MTHF may be a preferable treatment option for MDD in case patients do have a genetic polymorphism hindering their ability to convert folic acid.[4] In a double-blind, placebo-controlled study, researchers studied the effect of 5-MTHF supplementation in addition to standard psychotropic medication in depression patients with borderline or definite folate deficiency.[5] Researchers found that supplementation significantly improved clinical recovery in these patients. Researchers also supplemented elderly depressed patients who had normal folate levels and found improvement in symptoms after three weeks of treatment.[5] In another arm of the study, researchers assessed the effect of 5-MTHF supplementation on elderly patients with normal folate levels with mild to moderate dementia and depression compared to trazodone.[5]

For more information visit: www.nfh.ca

IHP 2014-10,11 (L-5-MTHF SAP).indd 2

There is a significant body of research that suggests improving folate status periconceptionally reduces the risk of neonatal neural-tube defects.[7] Therefore, increased folate intake is currently recommended before and during the early stages of pregnancy.[7] Folic acid in its synthetic form (which is only found in supplements and fortified foods) lacks the coenzyme activity and must be reduced to its metabolically active form l-5-methyltetrahydrofolate within the cell.[7] l-5-methyltetrahydrofolate is the predominant form of dietary folate and the only species normally found in circulation; therefore, it is the form that is normally transported into peripheral tissues and used for cellular metabolism.[7] Studies comparing folic acid to l-5-methyltetrahydrofolate have found that both compounds are comparable in terms of physiological activity, bioavailability, and absorption. [7] Supplementing with the l-5-methyltetrahydrofolate form may have an advantage over folic acid, because it is the form found in circulation and is associated with a reduced interaction with drugs that inhibit dihydrofolate reductase; also, there is less masking of the haematological symptoms of a vitamin B12 deficiency.[7] l -5-Methyltetrahydrofolate is the most active form of folate found in plasma, and it is able to directly enter the metabolic process.[8] Compared to folic acid, l-5-methyltetrahydrofolate shows optimum absorption as well as comparable or higher bioavailability and physiological activity.[8] l-5-Methyltetrahydrofolate supplementation is effective at decreasing plasma homocysteine and in increasing folate in both plasma and erythrocytes in women who were pregnant, breast-feeding, or trying to conceive.[8] There have been no reported adverse or toxic effects of supplementation with 5-MTHF. Based on current literature, 5-MTHF could be an effective and safe alternative to folic acid supplementation and could effectively prevent birth defects and pregnancy complications.[8]

REFERENCES 1.

2.

3.

4.

5.

6.

7.

8.

Ueland, M., et al. “Biological and clinical implications of the MTHFR C677T polymorphism”. Trends in Pharmacological Science Vol. 22, Issue 4 (2001): 195–201. http://lpi.oregonstate.edu/infocenter/vitamins/fa/ ∙ Accessed August 12, 2014 Fava, M. and D. Mischoulon. “Folate in depression: efficacy, safety, differences in formulations, and clinical issues”. The Journal of Clinical Psychiatry Vol. 70, Suppl. 5 (2009): 12–17.

Papakostas, G.I., C.F. Cassiello, and N. Iovieno. “Folates and S‑adenosylmethionine for major depressive disorder”. Canadian Journal of psychiatry Vol. 57, No. 7 (2012): 406–413.

Passeri, M., et al. “Oral 5′‑methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double‑ blind multicenter study”. Aging (Milano) Vol. 5, No. 1 (1993): 63–71.

Lamers, Y., et al. “Supplementation with [6S]‑5‑methyltetrahydrofolate or folic acid equally reduces plasma total homocysteine concentrations in healthy women”. The American Journal of Clinical Nutrition Vol. 79, No. 3 (2004): 473–478.

Pietrzik, K., L. Bailey, and B. Shane. “Folic acid and l‑5‑methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics”. Clinical Pharmacokinetics Vol. 49, No. 8 (2010): 535–48.

Seremak‑Mrozikiewicz, A. “[Metafolin — alternative for folate deficiency supplementation in pregnant women]” (article in Polish). Ginekologia Polska Vol. 84, No. 7 (2013): 641–646.

© NFH Nutritional Fundamentals for Health 2014

2014-09-18 9:50:52 AM

L-5-MTHF SAP

Science-based metabolically active folic acid Folic acid, or folate, is a B vitamin that must be derived from either dietary sources or via supplementation. Folate is necessary for a biochemical process in the body called “methylation” or “one-carbon metabolism”.[1] This process does not work adequately in a significant number of individuals who have a genetic polymorphism, and it may contribute to a host of different concerns, including neural tube defects, depression, and reduction in red blood cell production.[1] When the body absorbs folate, it goes through a series of biochemical conversions to become the active form l-5-methyltetrahydrofolate.[1] If an individual is unable to convert the folate properly, they can end up with a deficiency, even though they are eating foods containing folate. Folate is found in leafy green vegetables, legumes, beans, liver, yeast, and citrus fruits.

Each vegetable capsule contains:

ACTIVE INGREDIENTS

l-Methylfolate

(from calcium l-5-methyltetrahydrofolate) . . . . . . . . 1 mg

Contains no: Artificial flavour or colour, sugar, salt, yeast, starch, corn, soy, wheat, gluten, dairy, citrus, or eggs.

L‑5‑MTHF SAP contains 60 capsules per bottle.

ADULT DOSAGE

Take 1 capsule daily with food or as directed by your health-care practitioner.

INDICATION

ɶ L‑5‑MTHF SAP helps support red blood cell formation. ɶ L‑5‑MTHF SAP reduces the risk of neural tube defects if taken prior to and during early pregnancy. ɶ L‑5‑MTHF SAP may help to reduce homocysteine levels. ɶ L‑5‑MTHF SAP may prevent folate deficiency, which can lead to symptoms of depression.

CAUTIONS AND WARNINGS

Folate supplementation can mask a vitamin B12 deficiency; consult a health-care practitioner if you are uncertain whether or not you are taking adequate amounts.

PURITY, CLEANLINESS AND STABILITY

Third-party testing is performed on the finished product to ensure L‑5‑MTHF SAP is free of heavy metals, 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

IHP 2014-10,11 (L-5-MTHF SAP).indd 1

2014-09-18 9:50:51 AM

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