IHP Magazine - June/July 2013

IHP JUNE/JULY 2013 | $14.95 PUBLICATIONS MAIL 40678000 | 60 BLOOR STREET WEST SUITE 1106 | TORONTO ONTARIO, M4W 3B8

DHEA Part II

Sports Nutrition

Insomnia

By Heidi Fritz, MA, ND

By Eva M Selhub, MD and Alan C. Logan, ND

By Rochelle Fernandes MSc, ND (cand)

Integrated Healthcare

Practitioners

Farid Wassef, BSc Pharm, RPh Bridging the Gap

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Continuing Education

Effectiveness of Intravenous Vitamin C in Combination with Conventional Chemotherapy in Cancer Treatment: A Review

By James Bao, et al.

13-06-10 10:30 AM

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1. Allen S.J. et al. Dietary supplementation with lactobacilli and bifidobacteria is well tolerated and not associated with adverse events during late pregnancy and early infancy. J Nutr 2010; 140: 483-488.

2. 1.Williams EA,etetal.al.Dietary Clinicalsupplementation trial: a multistrainwith probiotic preparation significantlyis well reduces symptoms of irritable bowel in a double-blind placebo-controlled study. 2009; Allen S.J. lactobacilli and bifidobacteria tolerated and not associated withsyndrome adverse events during late pregnancy and early infancy. infancy J Nutr29(1): 2010;97-103.

140: 483-488.

Williams al. Clinical trial: a multistrain probiotic preparation reduces symptoms irritable bowel in a double-blind placebo-controlled study.

29(1): 97-103.2005; (6): 1091 3. 2.Madden JA,EA, et al.et Effect of probiotics on preventing disruption of thesignificantly intestinal microflora followingofantibiotic therapy:syndrome a double-blind, placebo-controlled pilot study.

Int 2009; Immunopharmacol.

3. Madden JA, et al. Effect of probiotics on preventing disruption of the intestinal microflora following antibiotic therapy: a double-blind, placebo-controlled pilot study. Int Immunopharmacol. 2005; (6): 1091

These statements have notnotbeen treat, cure, cure,ororprevent preventany anydisease. disease.

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New New HMF HMF probiotic probiotic formulas formulas for for IBS IBS relief relief and and post post antibiotic antibiotic therapy therapy

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HMF IBS Relief is clinically proven to significantly reduce the HMF HMF IBS IBS Relief Relief is is clinically clinically proven proven to to significantly significantly reduce reduce the the severity of symptoms of IBS and days with pain, while improving severity of symptoms of IBS and days with pain, while improving severity of symptoms of IBS and days with pain, while improving satisfaction satisfaction with with bowel bowel habits habits and and overall overall quality quality of of life life during during satisfaction with bowel 2habits and overall quality of life during the course course of of the the study. study.22 the the course of the study.

Clinical trials concluded that HMF Antibiotic Care effectively Clinical Clinical trials trials concluded concluded that that HMF HMF Antibiotic Antibiotic Care Care effectively effectively modulates the response of the intestinal microflora the effects modulates the response of the intestinal microflora to modulates the response of the intestinal microflora to to the the effects effects 4 4 of antibiotic therapy. of antibiotic therapy.4 of antibiotic therapy.

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Sheffield IBS IBS Trial Trial Clinical Clinical Data: Data: Williams, Williams, Plummer Plummer et. et. al. al. (2008) (2008) Clinical Clinical trial: trial: aa multistrain multistrain probiotic probiotic preparation preparation significantly significantly reduces reduces symptoms symptoms of of irritable irritable blowel blowel syndrome syndrome in in aa double-blind double-blind placebo-controlled placebo-controlled study. study. Aliment Aliment Pharmacol Pharmacol Ther.

Ther. 29:97-103.

29:97-103.

Sheffield Madden J.A.J. J.A.J. et al. al.Clinical EffectData: of probiotics probiotics onPlummer preventinget.disruption disruption ofClinical the intestinal intestinal microfloraprobiotic followingpreparation antibiotic therapy: therapy: double-blind, placebo-controlled pilot study. study.

Int Immunophar Immunophar 2005: placebo-controlled 5: 1091-1097.

1091-1097. study. Aliment Pharmacol Ther. 29:97-103.

Madden et Effect of on preventing the microflora following antibiotic AA double-blind, placebo-controlled pilot Int 2005: 5: Sheffield IBS Trial Williams, al. (2008)of trial: a multistrain significantly reduces symptoms of irritable blowel syndrome in a double-blind Susan F. Plummer et al.

Effects of probiotics on the composition of the intestinal microbiota following antibiotic therapy.

International Journal of Antimicrobial Agents 2005: 26: 69-74 Madden J.A.J. et al. Effect of probiotics on preventing disruption of the intestinal microflora following antibiotic therapy: A double-blind, placebo-controlled pilot study. Int Immunophar 2005: 5: 1091-1097.

Susan F. Plummer et al. Effects of probiotics on the composition of the intestinal microbiota following antibiotic therapy. International Journal of Antimicrobial Agents 2005: 26: 69-74

These statements have not been evaluated by Health Canada. These products are not intended to diagnose, treat, cure, or prevent any disease.

These statements have not been evaluated by Health Canada. These products are not intended to diagnose, treat, cure, or prevent any disease.

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from the publisher

Connect With Us

Primary Care 2013

J

ust recently we attended Primary Care in Toronto and the turnout was incredible! They did a very good job putting the conference together. The IHP booth was once again swamped with questions and inquires – our team was very pleased with the interest generated from MD’s, and the eagerness with which they were wanting to sign up to receive the publication. We thank all our advertisers and readers for your support. Our mission six years ago when we launched IHP was to work towards bridging the gap between conventional and integrative healthcare providers. We seem to be getting there, one MD at a time! The compliments we received were heart warming... We continue to serve you and strive to exceed your expectations! We welcome your comments and suggestions so that we continue to give you what you are looking for.

I have been thinking a lot lately about how pervasive technology has become in our lives, most notably our mobile devices... People crossing the street ticking away at their phone, while driving, in the middle of a conversation... Such technology has certainly made us much more efficient, yet at the same time we need to learn to use it appropriately... I must admit I am at times guilty of overusing such technology, something my children remind me of routinely...

I think there is value in putting the device away from time to time!

My first test was to put it away while in the garden... So if you don’t get a reply from me immediately, my garden is receiving some needed attention!

Sanjiv Jagota Publisher

4 www.ihpmagazine.com l June/July 2013

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Hepato DR® Liver Tonic and Detoxifier

Product Monograph for IHP, June/July 2013

By Terry Vanderheyden, ND

Get Healthy, Glowing Skin with Hepato DR® (aka Milk Thistle Combo) The Skin Doesn’t Lie One thing that has always struck me when looking at photos of my grandparents when they were young is how utterly perfect their complexions were. They were all born in the 19th century. In modern times, on the other hand, in our highly industrialized and polluted society, it seems many people have skin issues, whether acne, dryness, flaking, blemishes, or just plain nasty looking skin! Pollution is one of the main causes of problem skin (Siddons 2013).

Getting to the Root of the Problem The root of these problems is toxicity, and it is ultimately the liver’s job to remove it from the system. In today’s world, the liver is overworked, trying to keep up with the bombardment of chemicals and toxins we are exposed to in our food, water, and environment. When the liver is stressed, the skin often bears the brunt of the body’s overload of toxins and breaks out in rashes, acne, and inflammation.

The Liver, It Don’t Get No Respect The liver is an under-appreciated organ. Almost everything we consume – food, drink, medications, supplements – is sent direct to the liver for processing. The liver is essential to proper blood sugar balance, the metabolism of toxins in the body, energy and vitamin storage, and numerous other metabolic functions.

Detoxification Starts in the Liver A good detox starts in the liver. The liver acts to induce enzymatic changes to toxins, conjugating them with glutathione in many cases, or otherwise making them watersoluble for easy flushing from the system via the kidneys and urinary tract. This is why most detox programs utilize herbs to maximize liver function, herbs like dandelion, globe artichoke, Oregon grape, wild yam, Culver’s root, and milk thistle.

Psoriasis and Milk Thistle According to herbalist Christopher Hobbs, 50% of psoriasis sufferers benefit from milk thistle (Hobbs 1992). “Milk thistle seed extract,” he goes on to say, “is the most remarkable herb for psoriasis.” A great place to start with inflammatory skin problems is the liver.

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Terry Vanderheyden, ND (Research Consultant) Terry Vanderheyden, ND, has practiced in Ontario since graduating from the CCNM in 1994, specializing in homeopathic, nutritional and botanical therapies. He also works as a research consultant to St. Francis Herb Farm, Inc. Terry lives in Barry’s Bay with his wife Laurie and their 6 children.

References: Sarah Siddons. “How to Protect Skin from Pollution” (Accessed 10-May-2013). http://health.howstuffworks.com/skincare/beauty/skin-and-lifestyle/protectskin-from-pollution4.htm Christopher Hobbs, Foundations of Health: The Liver & Digestive Herbal.

Capitola, CA: Botanica Press; 1992, p. 198.

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(mg per ml)

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Hepato DR® Vegicaps (340 mg capsule, 5:1 extracts): Medicinal Ingredient

Plant part

Amount per cap (mg)

Silybum marianum Taraxacum officinale Cynara scolymus Mahonia aquifolium Dioscorea villosa Leptandra virginica

Seed Whole plant Tops Root Root Root

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Quantity Crude Equivalent (mg) 320 mg 200 mg 190 mg 110 mg 100 mg 80 mg

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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 | Malcolm Brown Production Manager | Erin Booth (416) 203-7900 ext. 6110 Contributors Christopher Habib, ND, Philip Rouchotas, MSc, ND

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Advertising Information Sanjiv Jagota | Tel: (416) 203-7900 ext 6125 Email: sanjiv@ihpmagazine.com Paul Airut | Tel: (416) 203-7900 ext 6103 Email: paul@gorgmgo.com Jeff Yamaguchi | Tel: (416) 203-7900 ext 6122 Email: jeff@gorgmgo.com Jason Cawley | Tel: (416) 203-7900 ext 6134 Email: jason@gorgmgo.com Erin Poredos | Tel: (416) 203-7900 ext 6128 Email: erin@gorgmgo.com Circulation

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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 publisher’s liability shall not exceed the amount of the publisher’s charge for such advertising. No portion of this publication may be reproduced, in all or part, without the express written permission of the publisher. ihp magazine is pleased to review unsolicited submissions for editorial consideration under the following conditions: all material submitted for editorial consideration (photographs, illustrations, written text in electronic or hard copy format) may be used by ihr Media Inc. and their affiliates for editorial purposes in any media (whether printed, electronic, internet, disc, etc.) without the consent of, or the payment of compensation to, the party providing such material. Please direct submissions to the Editor, ihp magazine.

1 866 783-7504 www.cyto-matrix.com June/July 2013 l www.ihpmagazine.com 7

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contents

This Issue: June/July 2013 • Vol. 6 • No. 3

32 Farid Wassef, BSc Pharm, RPh

Cover Story

Departments

Bridging the gap

40 Harmony Health Centre Clinic Profile

Multi-disciplinary clinic providing integrative healthcare options

45 The Journal of IHP

Peer-reviewed articles on clinically revelant topics

Coming Next Issue ➜ Mushrooms and cancer management ➜ Acid-alkali balance ➜ Iron status and diabetes progression

4 Publisher’s Letter 11 Research News 20 Industry News 26 Calendar 27 Product Profiles 46 Editor’s Letter 50 Peer Review Board 54 Editorial Board 72 Continuing Education:

Effectiveness of Intravenous Vitamin C in Combination with Conventional Chemotherapy in Cancer Treatment: A Review

8 www.ihpmagazine.com l June/July 2013

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Stop the burn Start the healing

Rapid relief of heart burn and ulcers Helps to heal the gastric lining and prevent damage to the esophagus Prevents the growth and spread of Helicobacter pylori ADVANCED

ORTHOMOLECULAR RESEARCH

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Gastro Relief Monograph Heartburn: What We Now Know The mechanism behind gastroesophageal reflux disease (GERD) has been an evolving science. Thanks to continued research, we now understand that heartburn can occur for several reasons: these include gastric ulcers, which we now know are often caused by an H. pylori infection, or a lack of stomach acid to trigger the lower esophageal sphincter (LES) to close. In light of this understanding, treating all GERD cases with medication to reduce the acidity of the stomach is narrow minded and provides only temporary relief since excessive stomach acidity only occurs in a small percentage of heartburn sufferers. The problem with acid reflux is not that the stomach is too acidic; often the reverse is actually true. If the stomach contents are not acidic enough, the LES does not close and the stomach contents back up into the esophagus, causing pain, irritation, and damaging the esophageal tissues which increases the risk of esophageal cancer.

A Well‐Rounded & Multi‐Targeted Approach The premise behind Gastro Relief™ is to provide quick and effective relief from the symptoms of heartburn while addressing any fundamental pathology which might be the cause of the problem. Gastro Relief’s ingredients include mastic gum, zinc‐carnosine, vitamin C, potassium nitrate and alginic acid.

Target: H. pylori Mastic gum has been shown to wipe out H. pylori, the cause behind the majority of gastric and duodenal ulcers. H. pylori damages cells of the stomach lining, impairing their ability to produce hydrochloric acid. Clinical studies have clearly shown its effectiveness with 80% of patients receiving mastic gum for 2 weeks reporting significant improvements in their symptoms. Further test tube studies confirmed that mastic gum kills H. pylori in concentrations easily attainable through supplementation. Animal studies also show that zinc‐carnosine prevents the development of H. pylori‐related gastritis. Untreated H. pylori is also a major contributor to gastric cancer.

Target: Low Stomach Acidity The acidic nature of Vitamin C helps lower the pH of the stomach, which increases the chances of the LES closing properly and reducing the risk of heartburn. The presence of ascorbic acid also enhances the conversion of dietary nitrate and salivary nitrite to NO by gastric juices. Those with H. pylori infections often have been found to have reduced ascorbic acid levels in their gastric secretions.

Target: Healing Cells of the Stomach Lining Cells damaged by H. pylori or by suboptimal stomach conditions during digestion cannot produce sufficient HCl and also pose an increased risk for gastric cancer.

Zinc‐carnosine has received much attention lately due to its ability to up‐regulate key antioxidant enzymes thereby preventing free radicals from damaging cells.

Animal and human studies have confirmed that zinc‐carnosine has anti‐ulcer properties and prevents gastric mucosal injury. Nitric oxide (NO), produced in the stomach when nitrate is consumed, contributes to healing of the stomach lining. Studies clearly demonstrate that NO is an effective anti‐inflammatory agent with protective effects against gastritis. NO is a potent vasodilator and increases blood flow to the gastric mucosa enhancing repair and the inflow of nutrients and oxygen. Higher NO levels in the stomach have also been shown to increase effective peristalsis movements.

Target: Relieving Heartburn & Protecting the Esophagus When it comes to relieving heartburn quickly, alginic acid is the key ingredient. Clinical studies clearly demonstrate the protective role of alginic acid, protecting the esophagus from the damaging potential of the refluxate, not merely the acid. This has led some experts in the field to lean towards natural products such as alginate rafts to address the problem instead of using more conventional approaches. This “raft” has two effects: it prevents the gastric contents from being pushed back up the esophagus and also coats the esophagus if the gastric contents were to reach the esophagus. Since it acts as a barrier and not simply by neutralizing the acidity or by preventing acid from being generated in the stomach, the alginic acid also protects the esophagus from the pepsin and bile salts found in the stomach and also known to damage the upper digestive tract. Researchers have confirmed that alginic acid is more effective than ranitidine and omeprazole, two drugs used in reflux, during the first hour after dosing.

Clinical Indications & Safety AOR’s Gastro Relief is designed for those dealing with GERD, H. pylori infection, gastric ulcers or gastritis and to promote the healing of damaged and impaired GI tissues that may have resulted.

SUPPLEMENT FACTS Serving Size:

2 Capsules

Zinc‐Carnosine

75 mg

Mastic Gum (Pistacia lentiscus)

500 mg

Potassium Nitrate

202 mg

Vitamin C (Ascorbic acid)

100 mg

Key non‐medicinal ingredient:

Sodium Alginate

300 mg

ADULT DOSAGE: Take 2 capsules daily with food, or as directed by a qualified health care practitioner. Do not use if pregnant or nursing or with erectile dysfunction‐ type products.

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research news Intestinal microbial metabolism of phosphatidylcholine impacts cardiovascular risk

Weight loss and exercise beneficial to chronic disease in postmenopausal women This study investigated the effects of dietary weight loss and exercise on the hormonal levels of adiponectin and leptin in overweight and obese postmenopausal women. Elevated body weight and sedentary lifestyle have been strongly linked to multiple chronic diseases, including cardiovascular disease, diabetes, and cancer. The authors wanted to investigate if alterations in adipose-derived adiponectin and leptin levels played a role. 439 overweight and obese postmenopausal women were randomized to a reduced calorie diet, moderate-to-vigorous intensity aerobic exercise, a combination of both, or a

control group. The reduced calorie diet had a 10% weight-loss goal. The exercise intervention was 45 minutes of aerobic activity 5 days per week.

Hormone levels of adiponectin and leptin were measured at baseline and one year later using radioimmunoassay.

The results showed that adiponectin increased by 9.5% in the diet group and 6.6% in the diet and exercise group.

Leptin decreased with all interventions compared to control. The degree of weight loss was inversely associated with concentrations of adiponectin and directly associated with leptin.

The authors conclude that weight loss and exercise exert beneficial effects on chronic disease via effects on these hormones. J Intern Med. 2013 Feb 25.

PMID: 23432360

Differences between users of CAM among those with multiple sclerosis This study investigated differences in socio-economic characteristics and the use of conventional treatments between complementary and alternative medicine (CAM) users and those who did not use CAM, in people who were diagnosed with multiple sclerosis (MS) in Denmark.

The authors utilized an internet-based questionnaire to collect data from 3361 patients of the Danish MS society. The final response rate was 55.5%. The results of the survey showed that people with MS in Denmark use a wide range of CAM treatments for a variety of reasons. CAM users were more likely to be female, 18-40 years of age, educated at the bachelor level or above, and have a high income compared to CAM non-users. In addition, CAM users also more often addressed preventive treatment purposes through their use of CAM treatments and they communicated less often with a medical doctor about the CAM treatments that they used. CAM users experienced less side effects and less positive effects from the CAM treatments used when compared with the use of conventional treatments among CAM non-users. The authors conclude there are numerous differences in the characteristics of those who use CAM. Scand J Public Health. 2013, Apr 2. PMID: 23548494

This study investigated the relationship among intestinal microbiotadependent metabolism of dietary phosphatidylcholine, trimethylamineN-oxide (TMAO) levels, and adverse cardiovascular events. Recent animal studies had shown a link between the metabolism of choline moiety in dietary phosphatidylcholine (lecithin) and

coronary artery disease through the production of the proatherosclerotic metabolite TMAO. The researchers quantified plasma and urinary levels of TMAO and plasma choline and betaine levels. This was done by means of liquid chromatography and online tandem mass spectrometry after a phosphatidylcholine challenge (2 hard boiled eggs and d9-labeled phosphatidylcholine) in healthy participants before and after the suppression of intestinal microbiota with oral broad-spectrum antibiotics. The 4007 participants were then followed for 3 years and underwent elective coronary angiography. The results of the study showed that there are timedependent increases in levels of TMAO and other choline metabolites, detected after the phosphatidylcholine challenge.

Plasma levels of TMAO reappeared after withdrawal of antibiotics.

Increased plasma levels of TMAO were associated with an increased risk of a major cardiovascular event, even after adjustment for traditional risk factors and in lower-risk subgroups, determined by the elective coronary angiography.

N Engl J Med. 2013, Apr 25. PMID: 23614584 June/July 2013 l www.ihpmagazine.com 11

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

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research news Intermittent fasting may help those with diabetes and cardiovascular disease In this review article, the authors explore the use of intermittent fasting, whereby people fast on consecutive or alternate days, and its ability to facilitate weight loss and improve cardiovascular risk. Various approaches to intermittent fasting are reviewed and the advantages and limitations for use of this approach are explored in the treatment of obesity and type 2 diabetes. An interesting 5:2 strategy has been developed where 2 days each week are classed as fasting days (with <600 calories consumed for men and <500 for women). This type of fasting has been shown to be similarly effective or more effective than continuous modest calorie restriction for weight loss, improved insulin sensitivity, and other biomarkers. Intermittent fasting has been known to be useful in the treatment of intractable obesity and morbidly obese individuals. Original treatment regiments were based upon intermittent starving as opposed to restricting calories, but despite the strict nature of the fasting days, it has a generally good adherence record and can cause significant reductions in body weight. The authors conclude that intermittent fasting offers the potential to improve weight loss and enhance the cardiovascular health of overweight and obese individuals. Sage. April 2013. PMID: Not Yet Available

Consumption of sweet beverages and link with type 2 diabetes This study investigated the association between the consumption of sweet beverages such as juices, nectars, and soft drinks with the incidence of type 2 diabetes in European adults. This casecohort study included 12,403 incident cases of type 2 diabetes and a stratified subcohort of 16,154 participants selected from eight European cohorts in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards regression models and random-effects meta-analyses were used to estimate the association.

Validated dietary questionnaires were used to assess the sweet beverage

consumption. The results showed that one 336g or 12oz daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 (95% CI 1.09, 1.38) and 1.52 (95% CI 1.26, 1.83), respectively. After further adjustments for energy intake and BMI, the association persisted for sugar-sweetened soft drinks but became statistically not significant. Juice and nectar consumption was not associated with the incidence of type 2 diabetes.

The authors conclude that this study confirms the association of sugarsweetened soft drink consumption and the incidence of type 2 diabetes in European adults. Diabetologia. 2013 Apr 26. PMID: 2360057

High long-term cortisol levels as measured in hair associated with cardiovascular disease This study examined the link between stress and the increased association with cardiovascular disease. The impact of chronic stress on cardiovascular risk has been studied by measuring cortisol in serum and saliva, usually

only measurements at a single time point. Measuring cortisol in scalp hair is a novel method to evaluate longterm cortisol exposure. In this study, a group of 283 community-dwelling elderly participants were randomly selected from a large population-based cohort study (median age 75). Cortisol was measured in 3-cm hair segments, corresponding roughly with a period of 3 months. Self-reported data about coronary heart disease, stroke, peripheral artery disease, diabetes mellitus, and other chronic noncardiovascular diseases were collected. The results showed that hair cortisol levels were significantly lower in women than in men. High hair cortisol levels were associated with an increased risk of cardiovascular disease (OR 2.7, P=0.01) and an increased risk of typ2 diabetes mellitus (OR 3.2, P=0.04). There were no associations between hair cortisol levels and noncardiovascular diseases.

The authors conclude that elevated long-term cortisol levels are associated with a history of cardiovascular disease, equivalent to the risk of traditional risk factors. J Clin Endocrinol Metab. 2013 Apr 17. PMID: 2356141

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

Twice the Strength! Double the Power!

Bio-Fen® Plus for Men: The mechanism that causes AGA in men follows the same pathway that results in benign prostatic hyperplasia (BPH). For example, the prescription drug finasteride also works by blocking the enzyme 5αreductase and is used as a treatment for both BPH and AGA. For AGA it is marketed under the brand name of Propecia, but the exact same molecule for BPH is sold under the name of Proscar.

Hair Grow Technology’s Bio-Fen® product line is continually moving forward! We are introducing our two latest versions; Bio-Fen® Plus for Men and Bio-Fen® Plus for Women. These products have been assigned Natural Product Numbers (NPN’s) by the Natural Health Products Directorate (NHPD) of Health Canada.

We recognize that both men and women experience androgenic alopecia (AGA, or male / female pattern baldness) and have made some improvements to the original formulation based on the latest science to address their specific needs. You will notice that we now have additional complementary (Health Canada Approved) health claims on each product.

What causes hereditary hair loss?

Each hair grows from a pocket in the skin called the hair follicle.

During its growing phase the follicle has a bulb-shaped bottom, the center of which is called the dermal papilla. The paplla is fed by very small blood vessels, which bring it food, oxygen and remove wastes.

The papilla is highly sensitive to hormones and chemicals secreted by the body (or ingested as a medicine) which impacts hair growth It is believed that some individuals have a genetic predisposition to a receding hairline (most common in men) or hair (follicle) thinning over larger areas of the scalp (more common in women). These conditions result from hormonal changes caused by an enzyme in the dermal papilla called 5-alpha-reductase. This enzyme breaks down the hormone testosterone into dihyrotestosterone (DHT). Over a period of time, an over abundance of DHT causes the hair follicle to degrade and shortens the active phase of the hair, eventually leading to thinner hair and eventual hair loss.

How does Bio-Fen® PLUS work?

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

As before, the saw palmetto extract inhibits the enzyme 5-alpha reductase, and this action slows down the conversion of testosterone to dihydrotestosterone (or DHT) – the overabundance of which causes the miniaturization of hair follicles. This activity of the saw palmetto also helps to relieve the urinary symptoms of mild to moderate BPH for men.

The saw palmetto that originally was an extract standardized to 45% free fatty acids, esters, and sterols while the new formula is a 4:1 extract to support the BPH claim. The product still contains these molecules for hair loss, but they are now at proprietary amounts based on our research so that the competition cannot duplicate our formula.

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

• Reduce elevated blood lipid levels / hyperlipidemia.

Bio-Fen® Plus for Women: The women’s formula is almost the same as the men’s formula. The mechanisms and results for the women formula is the same. The only difference is it contains silicon and iron instead of saw palmetto.

Silicon has been shown to contribute to hair shaft strength and thus healthy hair growth. It also contains iron which helps prevent iron deficiency. A number of studies have related sub-clinical iron deficiency in women to diffuse hair loss/alopecia.

The increased amount of SDG and other revisions to the regulations allow us to make some additional health claims for Bio-Fen® Plus for Women.

Available at Health Food Stores and Independent Pharmacies

Hair Grow Technology Inc.

IHP FP template-HairGrow.indd 1

•

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

• Metabolize carbohydrates, fats and proteins.

How long must I use Bio-Fen® Plus?

Bio-Fen® Plus for Men capsules are usually effective at stopping hair loss within the first two months. However, since healthy hair grows only about 1 cm each month, it may take up to three months before you notice that hair growth is increased or the rate of hair loss is decreased. Anyone experiencing new growth should see it within four months. In some people the original pigmentation may come back.

Once you stop completely your hair growth pattern will slowly go back to the point where you started. However, some people may be able to go with a lower maintenance dose.

Why has the recommended dose doubled?

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

How safe is Bio-Fen® Plus?

The ingredient combination in Bio-Fen® Plus is generally safe for most adults. However, the following cautions are advised: For Men: Consult a health care practitioner prior to use to exclude a diagnosis of prostate cancer, or if you have diabetes. For BPH or elevated blood lipid levels, consult a health care practitioner if symptoms persist or worsen. People sensitive to niacin may experience flushing of the skin that is generally mild and transient. Discontinue use if you experience hypersensitivity to flax, such as an allergy (may occur in rare cases).

For Women: Consult a health care practitioner prior to use if you are pregnant or if you have diabetes. Consult a health care practitioner if elevated blood lipid levels persist or worsen. People sensitive to niacin may experience flushing of the skin that is generally mild and transient. Discontinue use if you experience hypersensitivity to flax, such as an allergy (may occur in rare cases). Because of the iron content, some people may experience constipation, diarrhea and/or vomiting. Keep out of the reach of children. There is enough iron in this package to seriously harm a child.

1-866-424-7745 • www.biofen.com

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

Without treatment, AGA is progressive, and causes social distressfor in many men and women (Sinclair 1998). Bio-Fen Plus contains extracts BIO-FEN Men and BIO-FEN for Menaffected andWomen Women of fenugreek seeds, saw palmetto berries and flax lignans, as well as specific vitamins. Each ingredient is known to possess inhibitors of the enzyme 5α-reductase. inhibitors are responsible for relieving symptoms associated withPlus hereditary AGA. Bio-Fen represents line by for and Bio-Fen for Bio-Fen Bio-Fen representsaaThese lineofofproducts productsapproved approved byHealth HealthCanada Canada forhair hairgrowth growth andrestoration. restoration.

Bio-Fen Plus forMen Menand and Bio-FenPlus Plusfor forWomen Womenare areboth bothoral oralnatural naturalhealth health products hair growth women with alopecia (AGA), pattern baldness. contains aacombination ofof One (NHPs) of the which primary causes hairinloss isand a high level ofhereditary the maleandrogenic hormone dihydrotestosterone (DHT) within the Bio-Fen hair follicle (Vierhapper, 2001). products (NHPs) whichsupport support hairof growth inmen men and women with hereditary androgenic alopecia (AGA),ororfemale/male female/male pattern baldness.

Bio-Fen contains combination herb extracts and vitamins &&minerals that inhibit enzyme 5!-reductase aakey implicated ininthe of herb extracts andwith vitamins minerals thatare areknown known inhibitthe the enzymeof 5 androgen -reductase(5AR), (5AR), keypathway pathway implicated theprogression progression ofAGA. AGA. catalyzes the enzymatic For people AGA, their follicles have to atogreater number receptors to which DHT attaches.

5-α-reductase conversion of testosterone to dihydrotestosterone, which binds to the receptor five-fold more avidly than the parent compound (Sinclair 1998).

AGA AGAPathophysiology Pathophysiology

One Oneofofthe theprimary primarycauses causesofofhair hairloss lossisisaahigh highlevel levelofofthe themale malehormone, hormone,dihydrotestosterone dihydrotestosterone(DHT) (DHT)within withinthe thehair hairfollicle follicle(Hoffmann (Hoffmann2002).

2002).DHT DHTisisproduced producedfrom from testosterone ininthe the over Saw palmetto (Serenoa repens) testosterone thetestes testes(males), (males), theadrenal adrenalglands, glands,and andthe thefollicle. follicle.After Afteraaperiod periodofoftime, time,an anVitamins overabundance abundanceofofDHT DHTcauses causesthe thehair hairfollicle follicletotodegrade degradeand andshortens shortensthe theactive active phase of the hair, eventually leading to thinning hair and eventual hair loss.

There is a familial tendency for stepwise miniaturization of the hair follicle and an increase ininthe phase of the hair,(lipophillic) eventually leading to thinning hairbeen and eventual Thereinhibitor is a familial In tendency forstudy stepwise the hair follicle and an increase theratio ratio a Polish of miniaturization 46 women whoof had symptoms of diffuse alopecia, calcium Standardized Serenoa extract has found tohair be loss. a potent ofoftelogen (resting phase) to anagen (growth phase) hairs, which is promoted by systemic and local effects of androgens.

Although everyone produces DHT, only those with aa four to telogen (resting phase) to anagen (growthtissue phase)DHT. hairs, which is promoteddose by systemic effects of was androgens.

Althou gh everyone thosemg with pantothenate orally administered twiceproduces a day inDHT, dosesonly of 100 for of 5α-reductase, resulting in decreased An open-label, responseand local higher number of androgen receptors in their hair follicles, binding sites for DHT, and greater androgen sensitivity experience hair loss (Prager 2002).

5AR is responsible for the higher of androgen in their binding sitesof fora DHT, and greater five androgen sensitivity experience hairinjected loss (Prager 5AR forrepeated the 30 days and months, and vitamin B6 was every2002). day for 20istoresponsible studynumber was conducted onreceptors 42 healthy maleshair to follicles, determine the effect combination conversion ofoftestosterone totodihydrotestosterone, which binds totothe same receptor, but five-fold greater affinity.

2002) conversion testosterone dihydrotestosterone, binds the sameandrogen androgen butwith with five-fold greater(Brzezińska-Wcisło affinity.(Hoffmann (Hoffmann2002, 2002,Trueb Trueb again after six months 2001).

It was2002) determined that vitamin of carotenoid astaxanthin and saw palmettowhich berry lipid extract on DHT receptor, and

B6 administered parenterally for a few weeks induces improvement in the hair testosterone levels (Angwafor 2008). The men were divided into two groups: Flax Flax condition for in subset women andFlax reduces hairare loss. one group received 800 mg/day of balancing the combination supplement and the other Flax lignans inhibit the 5AR, formation ofofthe that loss (Evans 1995). lignans converted Flax lignans inhibit theenzyme enzyme 5AR,thus thus balancing formation themale malehormones hormones thatare areresponsible responsible forahair hair lossof (Evans 1995).

Flax lignans are convertedby bythe thebody bodytoto group received 2000 mg/day ofestrogen the supplement for 14 days.

ANOVA-RM enterolactones, which compete with and for binding, and enterolactones, which compete with estrogen andtestosterone testosterone forreceptor receptor binding,showed andincrease increasesex sexhormone hormonebinding bindingglobulin globulin(SHBG), (SHBG),resulting resultingininlower lowerlevels levelsofoffree free(ie (ieactive) active) estrogen and Flaxseed has serum ofof17-beta-estradiol and significant within-group increases in shown serum testeosterone significant estrogen andtestosterone. testosterone.

Flaxseed hasbeen been showntototal toreduce reduce serumlevels levelsand 17-beta-estradiol andestrone estronesulfate sulfate(Hutchins (Hutchins2001), 2001),and andresults resultsininaashift shiftininestrogen estrogenmetabolism metabolismtoto Medicinal Ingredients Dose Per Capsule favor the less biologically active estrogens (Brooks 2004). decreases serum DHT baseline in both favor the lessin biologically activefrom estrogens (Brooks 2004).dose groups (P=0.05). There was no significant difference between dose groups with regard to the increase of

Fenugreek (Trigonella foenum graecum)

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

Saw palmetto berry extract containing

160 mg

Another study tested liposterolic extract of Serenoa repens (LSESr) and beta45% free fatty acids Saw Palmetto (men’s product) Saw Palmetto (men’s product) sitosterol inextract the treatment ofinhibitor males (23-64 of age) with mild to moderate AGA. Saw palmetto isisaapotent ofof5!-reductase, resulting inindecreased tissue DHT Saw palmetto extract potent inhibitor 5 years -reductase, resulting decreased tissue DHT(Prager (Prager2002).

2002).In Inaapilot pilotstudy studyof of26 26men menwith withmild mildtotomoderate moderateAGA, AGA,treatment treatmentwith with Flax lignans, standardized toblinded 20% assessors Six of 10 (60%) subjects were rated extract asextract improved atand thebeta-sitosterol final visit, thus establishing aacombination ofoflipophilic saw palmetto 200mg 50mg improved by asasscored combination lipophilic saw palmetto 200mg and beta-sitosterol 50mg improvedsymptoms symptoms byup uptoto60%, 60%, scoredby by blinded assessors(Prager (Prager 2002). InInaameta meta 100 2002). mg secoisolariciresinol diglucoside (SDG) analysis by group, has found totobe the effectiveness of 5α-reductase inhibitors against AGA (Prager 2002). as Chronic analysis bythe theCochrane Cochrane group,saw sawpalmetto palmetto hasalso alsobeen been found beeffective effective asaatreatment treatmentfor forsymptoms symptomsofofBPH BPH(Wilt (Wilt2002).

2002). inflammation of the hair follicle is considered to be a contributing factor for AGA. A

D-calcium pantothenate (Vitamin B5) 10.40 mg Silica (women’s product) Silica (women’s product) study

by Chittur et al sought to determine whether blockade of inflammation using Silica isisaatrace mineral that totoincrease hydroxyproline Silica tracetwo mineral thathas hasbeen beenfound found increase hydroxyproline concentration inconnective connectivetissue tissue(Barel (Barel2005).

2005).InInaarandomized, randomized,double doubleblind, blind,placebo placebocontrolled controlledstudy, study,50 50 LSESr and anti-inflammatory agents (carnitine and thiocticconcentration acid) could in alter Niacinamide (Vitamin B3) 10.25 mg visualanalog women with skin with asasorthosilicic acid (OSA) daily women withdamaged damaged skinwere weretreated treatedorally orally with10mg 10mgsilica silica orthosilicic acid (OSA) dailyfor for20 20weeks. weeks.The Thetreatment treatmentgroup groupreported reportedaasignificant significantdecrease decreaseininvisual analog the expression of molecular markers of inflammation (Chittur 2009).

It was found scale brittle hair found that blind,placebo placebocontrolled controlledtrial trialconducted conductedinin50 50women womenwith that10mg 10mgsilica silicaasasOSA OSA scaleratings ratingsofofhair hairbrittleness brittleness(Barel (Barel2005).

2005).AAsecond secondrandomized, randomized,double doubleblind, Pyridoxine HCl (Vitamin B6) with brittle hair found 2 mg thatmonths the combination suppressedhair lipopolysaccharide-activated gene (thickness) expression(Wickett of for significantly elasticity, for99months significantlyimproved improvedhair elasticity,breakage, breakage,and anddiameter diameter(thickness) (Wickett2007).

2007). chemokines associated with pathways involved in inflammation and apoptosis.

Riboflavin (Vitamin B2)

1.58 mg

Folic acid

0.095 mg

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

Fenugreek 260 mg Fenugreek(Trigonella (Trigonellafoenum foenumgraecum) graecum)seed seedextract extract4:1 4:1.................................................... ....................................................260 mg Biotin 400 mcg equiv (dry equiv1040mg) 1040mg) Fenugreek(dry Seeds Flax lignans, toto50% ...............................................................................

100 mg Flax lignans,standardized standardized 50%SDG SDG ...............................................................................100 mg Non-Medicinal Ingredients Fenugreek seeds contain 5% to 30% protein, steroid saponins, sterols, flavonoids d-calcium 10.4 mg d-calciumpantothenate pantothenate(Vitamin (VitaminB5) B5) .................................................................................. ..................................................................................10.4 mg and alkaloids (notably trigonelline and choline).

Steroid saponins bind and Niacinamide 10.3 mg Niacinamide(Vitamin (VitaminB3) B3) ................................................................................................... ...................................................................................................10.3 mg Inert microcrystalline cellulose and vegetable-based magnesium eliminate extra cholesterol and hormones in the body; DHT is made from2.0 mg Pyridoxine HCl (Vitamin B6) mgstearate in a veggie-based capsule Pyridoxine HCl (Vitamin B6)............................................................................................... ...............................................................................................2.0 testosterone, which is in turn is made from cholesterol.

Therefore, when excess Riboflavin 1.6 mg Riboflavin(Vitamin (VitaminB2) B2)....................................................................................................... .......................................................................................................1.6 mg cholesterol is eliminated, less DHT can be made (Stark 1993). In a study of 2095 mcg Folic acid Folic acid .............................................................................................................................. ..............................................................................................................................95 mcg Biotin ....................................................................................................................................

Recommended adult dose: One capsule per day adults who consumed 12.5g and 18.0g of germinated fenugreek seed powder for250 mcg Biotin ....................................................................................................................................250 mcg

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

Men’s also Men’s alsohas: has: cholesterol and low-density lipoprotein (LDL) levels (Sowmya 1999).

Saw 125 mg Sawpalmetto palmettoberry berryextract extract4:1 4:1............................................................................................. .............................................................................................125 mg (dry (dryequiv. equiv.500 500mg) mg) Flax lignans

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

Iron (ferriccitrate) citrate) ................................................................................................................20 mg 2009). Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L

Recommended use: one capsules per Bio-Fen® Plus Recommended use:0.00 onecapsule capsuletwice twice daily (60 capsules perbottle). bottle).

Bio-Fen® Pluscapsules capsulesare areusually usuallyeffective effective (95% CI: -0.20, mmol/L) anddaily 0.08(60 mmol/L (95% CI: -0.16, 0.00 mmol/L), atatstopping first Anyone experiencing new should stoppinghair hairloss losswithin withinthe the firsttwo twomonths. months.

Anyonewith experiencing newgrowth growth should seeititwithin withinfour fourmonths. months. respectively.

Significant reductions were observed whole flaxseed (-0.21 and see Once Bio-Fen isisstopped, the growth pattern will return totoits point, Once Bio-Fen stopped, thehair hairand growth pattern willslowly slowly return itsoriginal original point,however howeversome somepeople peoplemay may -0.16 mmol/L, respectively) lignan (-0.28 and -0.16 mmol/L, respectively) be with aalower beable abletotocontinue continue with lowermaintenance maintenancedose. dose. supplements (Pan 2009).

Bio-Fen Bio-Fenhas hasbeen beenapproved approvedby byHealth HealthCanada Canadaand andhas hasreceived receivedaaunique uniqueNPN NPNnumber. number.InInaddition additiontotobeing beingapproved approved for forhair hairgrowth growthapplications, applications,Bio-Fen Bio-Fenhas hasbeen beenapproved approvedfor foradditional additionalhealth healthbenefits. benefits.

Angwafor F III, Anderson ML. An open label, dose the effect of a dietary supplement dihydrotestosterone, testosterone and estradiol levels in healthy males. J Contraindications: The ingredient combination in response Bio-Fenstudy Plus to fordetermine Men/Women is generally safe for most on adults.

Int Socshould Sportsnot Nutr Bio-Fen be2008;5:12. usedingredient by patientscombination with diabetes, or knownPlus hypersensitivity to any ingredients.

Contraindications: The in Bio-Fen for Men/Women is generally safe for most adults.

Bio-Fen should not be used by patients withB6 diabetes, or known hypersensitivity to any ingredients.

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

Brooks JD, et al. Am J Clin Nutr. 2004 Feb;79(2):318-25.

References Chittur S, Parr B, Marcovici G. Inhibition of inflammatory gene expression in keratinocytes using a composition containing carnitine, thioctic acid and saw palmetto extract. Evid Based Evans BA, 1995 Brooks JD,etetal.al.

Am Nov;147(2):295-302.

J Clin Complement Alternat Med Nutr.

2009. 2004 Feb;79(2):318-25.

Hoffmann Exp Dermatol.

2002 Jul;27(5):373-82.

Evans BA,R.etClin al. 1995 Nov;147(2):295-302.

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

Hutchins al. Exp NutrDermatol.

Cancer. 2001;39(1):58-65.

Hoffmann 2002 Jul;27(5):373-82.

Prager N, et al.

2002 Apr;8(2):143-52.

2001;39(1):58-65.

Hutchins AM,et al.K, Nutr Cancer.

Prager N, Bickett French N, Marcovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the Trüeb RM. Gerontol.

2002 Aug-Sep;37(8-9):981-90.

Prager N, etExp al.androgenetic 2002 Apr;8(2):143-52. treatment of alopecia.

J Altern Complement Med 2002;8:143-52.

Wickett RR, Exp et alGerontol.

Arch Dermatol Res. 2007 Dec;299(10):499-505.

Trüeb RM. 2002 Aug-Sep;37(8-9):981-90.

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

Wilt T et RR, al.repens Cochrane Syst Rev. 2002;(3):CD001423.

Wickett et almonograph.

ArchDatabase Dermatol Res. 2007 Dec;299(10):499-505.

Wilt T et al.

Database Syst Rev. 2002;(3):CD001423.

Sinclair R. Cochrane Male pattern androgenetic alopecia.

BMJ 1998;317:865-9.

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

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

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

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research news Mediterranean diet and risk of hyperuricemia in elderly at high cardiovascular risk

Prevention of migraines with pharmacologic treatments show all drugs comparable This study is a systematic review of the preventive pharmacologic treatments for community-dwelling adults with episodic migraines. Electronic databases were searched until May 2012. Studies were eligible to be included if they were randomized controlled trials (RCTs) of preventive drugs compared to placebo or active treatments examining rates of greater than 50% reduction in monthly migraine frequency or improvement in quality of life. The authors assessed risk of bias and strength of evidence and conducted random effects meta-analyses of absolute risk differences and Bayesian

network meta-analysis. The results included 215 publications of RCTs. 59 drugs from 14 drug classes were included.

All approved drugs, including topiramate (9 RCTs), divalproex (3 RCTs), timolol (3 RCTs), and propanolol (4 RCTs), offlabel beta blockers metoprolol (4 RCTs), atenolol (1RCT), nadolol (1 RCT), and acebutolol (1 RCT), angiotensinconverting enzyme inhibitors captopril (1 RCT) and lisinopril (1 RCT), and candesartan (1 RCT) outperformed placebo in reducing monthly migraine frequency by greater than 50% in 200400 per 1000 patients treated. The authors conclude that the approved drugs prevented episodic migraine frequency with no statistically significant difference between them. J gen Intern Med. 2013 Apr 17. PMID: 23592242

High dietary salt intake exacerbates H. pylori gastric carcinogenesis in animals This animal study examined the impact of a high salt diet and its association with Helicobacter pylori (H. pylori) induced carcinogenesis in gerbils. H. pylori is a risk factor in human gastric adenocarcinoma.

The process is dependent on a bacterial oncoprotein known as CagA. Epidemiological studies have shown that a high dietary salt intake is a separate risk factor for gastric cancer. In this study, Mongolian gerbils were infected with a wild-type (WT) CagA plus H. pylori strain or an isogenic CagA mutant strain and maintained with a regular diet or a high salt diet. At 4 months post-infection, gastricadenocarcinoma was detected in 100% of the WT-infected and high-salt diet animals, 58% of the WT-infected and regular diet animals, and none of the animals infected with the CagA mutant strain.

In those infected with the WT strain, those fed a high salt diet had more severe gastric inflammation, higher gastric pH, increased parietal cell loss, increased gastric expression of IL-1B, and decreased gastric expression of hepcidin and H,K-ATPase compared with those on a regular diet. The authors conclude that a high salt diet potentiates the carcinogenic effects of CagA plus H. pylori strains. Infect Immun.

2013 Apr 8. PMID: 23569116

This study examined the role that a Mediterranean-type diet (MeDiet) could play on potentially decreasing serum uric acid concentrations due to its antioxidant and anti-inflammatory properties. Crosssectional and prospective analysis was conducted in 4,449 elderly participants at high cardiovascular risk from the PREDIMED trial randomized to two

MeDiet interventions (supplemented with either olive oil or nuts) or a control diet. A validated questionnaire was used to assess adherence to the MeDiet.

Hyperuricemia was considered to be present when serum uric acid was higher than 7mg/dL in men or higher than 6mg/dL in women. The results showed that after a median follow-up of 5 years, 24.9% of the individuals who did not have hyperuricemia at baseline developed it, whereas 43.8% of the hyperuricemic individuals at baseline reverted to the condition. An inverse association was observed between increasing levels of adherence to the MeDiet score and decreasing hyperuricemia. Baseline consumption of red meat, fish and seafood, and wine were associated with a higher prevalence of hyperuricemia. The authors conclude that higher baseline adherence to the MeDiet is associated with a lower risk of hyperuricemia. J Gerontol A Biol Sci Med Sci. 2013 Apr 17. PMID: 23599357 June/July 2013 l www.ihpmagazine.com 17

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Discover Calm Within the Storm

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

Silexan™ is a trademark of Dr. Willmar Schwabe 1. Woelk H, Schläfke S. A multi-center, double-blind, randomized study of the Lavender oil preparation Silexan in comparison to [drug name] for generalized anxiety disorder. Phytomedicine 2010;17:94–9.

2. Kasper S, Gastpar M, Müller WE, et al. Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of ‘subsyndromal’ anxiety disorder: a randomized, double-blind, placebo controlled trial.

Int Clin Psychopharmacol 2010;25:277–87.

1.800.644.3211 • www.integrativeinc.com

IHPAPR2012_XXXX_ADVERTISER_Product_FP.indd 1

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TECHNICAL DATA

Lavela ws

Clinically Studied Lavender Oil

Background

Lavela ws 1265™ Clinically Studied Lavender Oil

Mild or occasional anxiety is a common complaint. Herbal preparations have long been a mainstay for maintaining a healthy, adaptive response to everyday stress and promoting restful sleep.

Lavandula angustifolia is the most common species of lavender utilized for health purposes.1 Lavender is native to the Mediterranean, the Arabian Peninsula, Russia and Africa. Throughout history, lavender has been cultivated for its flowers and oils and used both cosmetically and medicinally. Lavender has a high concentration of volatile oils; these oils are regularly used in aromatherapy to relieve mild anxiety.* Lavender has been also used internally for mood imbalances such as restlessness, occasional sleeplessness, and gastrointestinal complaints related to nervousness.*2 Lavender essential oil is obtained from steam distillation processing of the flowering tops of L. angustifolia.

1265™

Supplement Facts Serving Size 1 softgel Amount per softgel Lavender (Lavandula angustifolia) Oil (Silexan™ brand)

80 mg**

**Daily Value not established.

OTHER INGREDIENTS: canola oil, gelatin (capsule), glycerin, sorbitol, and annato extract color.

Lavela WS 1265™: Lavela WS 1265 is an exclusive, proprietary lavender (Lavandula angustifolia) essential oil, indicated for occasional anxiety.* Clinically shown to be comparable in efficacy to commonly used conventional and alternative options, Lavela WS 1265 offers safe and effective relief.

Contains no: sugar, salt, yeast, wheat, gluten, corn, dairy products, artificial flavoring, or preservatives. This product contains natural ingredients; color variations are normal.

• Exclusive, safe and effective option

CAUTION: Not to be used during pregnancy, lactation, or by persons under 18 years of age. If you are taking prescription medications, consult with your healthcare practitioner before using this product. Lavender eructation has been reported in a small number of users and is a normal effect of the product.

• Non-habit forming, non-sedating relief of occasional anxiety* • Convenient, once-daily dosing

Lavela WS 1265 Clinical Overview Several clinical studies show the benefit of Lavela WS 1265 as compared to reference or placebo. The results were statistically significant and the response rate to treatment is high.

Recommendations: Take one softgel daily with a full glass of water, or as recommended by your healthcare practitioner.

Integrative Therapeutics: 60ct / 70662 Emerson Ecologies: I06620 Natural Partners: IT0084

Comparison to conventional options Researchers Woelk and Schläfke conducted a multi-center, double-blind, randomized study of Lavela WS 1265 in comparison to a conventional agent for promoting relaxation.3 The Hamilton Anxiety Rating Scale (HAM-A total score) was used as the primary objective measurement to monitor changes in the level of tension and relaxation beginning at baseline through week 6 of the trial. Additional data was collected using the Self-Rating Anxiety Scale, Penn State Worry Questionnaire, SF 36 Health Survey Questionnaire and specific sections of the Clinical Global Impressions.

Comparison to kava and conventional alternatives Kava kava (Piper methysticum) was among better studied herbs for supporting relaxation, until concerns about liver toxicity prompted many companies to discontinue offering it.

In a 6-week study, kava was found to produce a mean reduction of the HAM-A score of 10 points, whereas the mean reduction of that score from WS 1265 has ranged from 11.3 points (6 week study)3 to 16 points (10 week study).4 Other conventional approaches have mean HAM-A reductions in the range of 11 to 15.3 points, suggesting comparable to superior efficacy of WS 1265 without the side effects associated with those options.3-7

A total of 77 female (76.6%) and male (23.4%) subjects 18-65 years of age were randomized into groups. Participants were eligible for the study if they met the inclusion criteria of a HAM-A total score of greater than 18 as well as a score equal to or greater than 2 on both anxious mood and tension items. Secondary objective outcome data were obtained from responder and remission rate comparisons made between the two treatment groups. In order for a participant to qualify as having a significant response to treatment they were required to have a reduction of at least 50% in the HAM-A total score during the six week trial. Remission was defined as a HAM-A total score of less than ten points at the end of the six week study. The clinical results demonstrated that WS 1265 was comparable to the conventional approach.

The HAM-A total score decreased by 45% in the WS 1265 group and decreased by 46% in the conventional group. At the conclusion of the six week intervention, 40% of the WS 1265 group and 27% of the conventional treatment group were determined to be in remission. The WS 1265 group had a response rate of 52.5% compared to only 40.5% taking the conventional option. Adverse effects in the WS 1265 group were uncommon and included nausea (5.2%), eructation (3.9%) and dyspepsia (2.6%).

Safety

Efficacy of WS® 1265 Another study was performed to investigate the efficacy of WS 1265 in comparison to placebo in a primary care setting.4 In 27 general and psychiatric practices, 221 adults reporting unspecified anxiety were randomized to receive 80 mg per day of WS 1265 or placebo for 10 weeks with office visits every 2 weeks. A baseline HAM-A total score of ≥18 and a total score > 5 for the Pittsburgh Sleep Quality Index (PSQI) were required. The primary outcome measures were HAMA and PSQI total score decrease between baseline and week 10. Secondary efficacy measures included the Clinical Global Impressions scale, the Zung Self-Rating Anxiety Scale, and the SF–36 (Quality of Life) Health Survey Questionnaire. Subjects taking WS 1265 showed a total score decrease by 16.0± 8.3 points (mean± SD, 59.3%) for the HAM-A and by 5.5± 4.4 points (44.7%) for the PSQI compared to 9.5± 9.1 (35.4%) and 3.8± 4.1 points (30.9%) in the placebo group (P < 0.01 one-sided, intention to treat). WS 1265 was superior to placebo regarding the percentage of responders (76.9 vs. 49.1%, P< 0.001) and remitters (60.6 vs. 42.6%, P=0.009). Adverse effects were uncommon and included dyspepsia (4.7% in the treatment group vs 1.8% in the placebo group) and eructation (3.7% in the treatment group and none in the placebo group).

The safety profile and evaluation report for WS 1265 showed no serious adverse events during either of the studies discussed above. Lavela WS 1265, when taken at the recommended dose of 80 mg per day, is safe and well-tolerated, without sedative action on the body, and no known potential for abuse.

Conclusion

Lavela WS 1265 offers a safe and effective solution for occassional anxiety.* It also promotes relaxation and restful sleep.* Taken just once a day, this gentle yet powerful botanical essential oil is non-habit-forming and well-tolerated, with efficacy demonstrated in controlled clinical trials published in peer-reviewed medical journals.

References 1. Basch E, Foppa I, Liebowitz R, et al. Monograph: Lavandula angustifolia. J Herbal Pharmacother 2004;4(2) 63-78.

2. Blumenthal M, ed. Lavender flower. In: The Complete German Commission E Monographs. Austin, TX, American Botanical Council, 1998:159–60.

3. Woelk H, Schläfke S. A multi-center, double-blind, randomized study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder. Phytomedicine 2010;17:94–9.

4. Kasper S, Gastpar M, Müller WE, et al. Silexan, an orally administered Lavandula oil

preparation, is effective in the treatment of ‘subsyndromal’ anxiety disorder: a randomized, doubleblind, placebo controlled trial. Int Clin Psychopharmacol 2010;25:277–87.

5. Woelk H, Kapoula O, Lehr S, Schröter K, Weinholz P (1999). A comparison of Kava special extract WS 1490 and benzodiazepines in patients with anxiety. Healthnotes Review 6:265–70.

6. Bielski RJ, Bose A, Chang CC. A double-blind comparison of escitalopram and paroxetine in the long-term treatment of generalized anxiety disorder. Ann Clin Psychiatry 2005 Apr-Jun;17(2):65–9.

7. Allgulander C, Hartford J, Russell J, et al. Pharmacotherapy of generalized anxiety disorder: results of duloxetine treatment from a pooled analysis of three clinical trials. Curr Med Res Opin 2007 Jun;23(6):1245–52. Epub 2007 Apr 25.

Lavela WS 1265 had a significant beneficial influence on quality and duration of sleep and improved general mental and physical health without causing any unwanted sedative effects.* Researchers concluded that Lavela WS 1265 was “both efficacious and safe” for the relief of occasional anxiety not otherwise specified.* It has a clinically demonstrable relaxing effect and was found to support restful sleep.*4 12-IT LLC-0160 REV 2/2012 #66840 * This sTaTemenT has noT been evaluaTed by The Food and drug adminisTraTion. This producT is noT inTended To diagnose, TreaT, cure, or prevenT any disease.

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industry news Health Canada Approves Genestra Brands® Health Claims for IBS Relief and Post Antibiotic Therapy

Genestra Brands® announced today that Health Canada has approved two significant claims related to its proprietary Human Micro Flora (“HMF”) probiotics – “Signicant reduction in the symptoms of irritable bowel syndrome (“IBS”)” and Effective supplementation of normal intestinal microbiota following antibiotic therapy”. Based on these claims, HMF IBS Relief™ and HMF Antibiotic Care™ were recently launched in Canada. “Considering that few products in the market target these specific conditions, we are pleased to receive Health Canada’s approval for the two claims related to the treatment of IBS and to post- antibiotic recovery. This is another example of our ongoing commitment to incorporate safe and effective formulas that reflect the latest evidence- based research. Under the direction of Dr. Nigel Plummer, Genestra Brands® HMF strains were meticulously selected and diligently tested in double- blind placebo controlled clinical trials” said Yves Yau, President as Seroyal.

BD Announces Launch of BD UltraSafe PLUS™ Passive Needle Guard

BD Medical, a segment of the leading global medical technology company, announced the commercial launch of a new passive needle guard technology, BD UltraSafe PLUS™. The BD UltraSafe PLUS™ Passive Needle Guard has received 510(k) clearance as an anti-needlestick safety device. This product, in addition to offering needlestick safety in an easy-to-use onehanded device, is enhanced with ergonomic features designed to facilitate comfort and support for healthcare providers and patients. In addition, this safety device is designed to meet increasingly complex biotechnology drug requirements, including higher viscosity. The BD UltraSafe PLUS™ Passive Needle Guard provides many advanced features including a robust plunger rod to help support injection of viscous drugs, a larger drug inspection window to improve drug visibility, extended built-in finger flanges and an enhanced plunger head for improved injection support and stability. These ergonomic improvements provide support for all users, including patients with diminished manual dexterity. BD recently conducted a clinical focus group with patients who had reduced dexterity and also suffered from rheumatoid arthritis and multiple sclerosis. Subjects reported that the BD UltraSafe PLUS™ Passive Needle Guard provided ease of use with 100% of injections executed successfully.

World’s First Treatment of Local Prostrate Cancer

Research facilitated by Lawson Health Research Institute at the London Health Sciences Centre (LHSC) has resulted in a new minimally invasive treatment option for patients with localized prostate cancer. Transurethral magnetic resonance (MR) guided ultrasound ablation treatment uses a new ablation device that uses thermal ultrasound therapy with real-time MR image guidance to eliminate cancer cells in the prostate gland. It provides physicians with a 360 degree viewing angle that allows the whole prostate gland to be treated in one session and with great accuracy. This reduces the significant long-term complications that normally accompany conventional treatments and also benefits patients with a smaller amount of cancer that is less likely to spread. The first procedure was done as part of a clinical trial approved by Health Canada and sponsored by Profound Medical Inc. with subsequent treatments performed in an experimental setting. An upcoming clinical trial will treat 30 patients with localized prostate cancer and follow their progress for the course of a year.

Vitality provides Business Update

Vitality attended and exhibited at the 2013 Canadian Health Food Association (CHFA) West Conference and Trade Show at the Vancouver Convention Centre, West Building, Vancouver, BC. The Company is a member of CHFA, Canada’s largest trade association dedicated to natural health and organic products. CHFA West is one of Canada’s largest trade shows for the natural health and organics industry. According to CHFA, the natural health product industry contributes $3 billion, and the organics product industry contributes $2 billion, to the Canadian economy. The Company had the opportunity to meet with retailers and provide information regarding select Vitality products and the Company’s new branding was unveiled. The Company is currently investigating opportunities to market and distribute its 90 products, including products with time release vitamins and minerals formulations.

Seroyal complying with Heath Canada’s NHPD Regulations

In 2004, Health Canada introduced The Natural Health Products Directorate (NHPD) as the regulating authority for natural health products in Canada. As per the Regulations, manufacturers were granted 10 years to secure mandatory product licenses and site licenses. For the last 10 years, Seroyal has worked closely with Health Canada to secure these licenses. As of May 2013, 100% of Seroyal’s sites have been licensed and 99.3% of their 1,688 products have secured Natural Health Product numbers (NHPs) and Homeopatic Medicine Numbers (DIN- HM). Seroyal will achieve 100% compliance well in advance of the September 2014 date set by Health Canada. As leaders in the natural health product industry, Seroyal is committed to providing practitioners with safe, effective products that they can trust. Seroyal’s commitment to Good Manufacturing Practices and the highest quality assurance standards sets them apart as an industry leader.

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Introducing...

Sereniten Plus

An effective solution consisting of Lactium®, L-Theanine and Vitamin D to reduce the symptoms of mental and physical stress.

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

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

VISIT US @ DOUGLASLABS.CA OR CALL TOLL FREE @ 866.856.9954

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Sereniten Plus

Anxiolytic effect reducing Mental and Physical Stress DESCRIPTION Sereniten Plus is a combination of Lactium®, L-Theanine and Vitamin D to support the HPA axis and feedback loop for stress management and cortisol regulation.

FUNCTIONS The neurochemical and hormonal reactions to stress are regulated through the Hypothalamic-Pituitary-Adrenal axis (HPA axis) designed for acute stressors that resolve rapidly. Present day chronic, low-grade stress results in the continual release of CRH (Corticotropin Releasing Hormone) from the hypothalamus. This chronic secretion causes dysfunction in the HPA axis, desensitizing the hypothalamic and pituitary receptors to negative feedback from adrenaline, noradrenalin and particularly, cortisol. Loss of negative feedback within the neuro-hormonal system results in a multitude of health issues. It increases the production of ADH, aldosterone, and angiotensin increasing vascular vasoconstriction and sodium retention. It increases C-reactive protein and endothelin, promoting atherosclerosis and inflammation. It directly increases LDL production as well as glucocorticoid and mineralcorticoid release, further increasing cardiac risk. When the negative feedback loop within the HPA-axis is disrupted, chronic hormonal secretion becomes “normal” for that individual. In this state, they either fail to recognize they are stressed, or they may experience exaggerated emotional and physical response to every stressor including intolerance to noise or light, or feeling overwhelmed by simple tasks. Stress affects so many aspect of health that is becoming crucial to rebalance the HPA-axis.

Lactium®, a bioactive decapeptide, alpha-1 sequence isolated from milk is effective in not only decreasing glucocorticoid secretion but will assist in rebalancing the HPA pathway. Lactium® works at three areas of the HPA-axis: 1) Lactium® binds specifically to the BZD site of the GABA-A receptor and does NOT bind to the PBR site of the GABA-A receptor responsible for the sedating effects seen with benzodiazepines.

2) Lactium® increases the sensitivity of the hypothalamus to cortisol, re-establishing receptor sensitivity feedback within the HPA-axis. It reduces the amount of CRH produced in response to stress.

3) Lactium® decreases the amount of cortisol released by the adrenal glands during acute and chronic stress.

Studies in humans using alpha-S1-casein hydrolysate have resulted in anxiolytic-like effects, without side effects.

Results showed a significant decrease in plasma cortisol throughout the combined stress tests and stable heart rate in the treatment group but not in the placebo group. Another study showed after 30 days of treatment a reduction in stress related symptoms including digestion, cardiovascular, intellectual, emotional, and social problems.

L-Theanine is a unique amino acid derived from tea providing relaxation support without drowsiness. L-Theanine has been shown to increase alpha-wave production, an observed pattern considered to be an index of relaxation.

Vitamin D has been included for additional support in reducing inflammation and supporting immune function.

INDICATIONS Sereniten Plus is for individuals wanting to support their response to stress and reestablish HPA-axis to stress.

FORMULA 201348 Each capsules contains: Casein decapeptide (milk)/ casein decapeptide (lait) (Lactium®) . . . . . . . . . . . . . . . . . . 175mg L-Theanine (Suntheanine®) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50mg Vitamin D3/Vitamine D3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100IU

SUGGESTED USE Adults take 1 capsule daily or as directed by your health care professional.

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

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industry news PEI first province to offer GARDASIL to boys in school

Prince Edward Island became the first province in Canada to extend its publicly funded school-based HPV vaccination program to boys. The program will use GARDASIL [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine], the only HPV vaccine indicated and recommended for boys and men. In 2007, The National Advisory Committee on Immunization (NACI) recommended the quadrivalent HPV vaccine to protect Canadian girls and women aged 9 to 26 against a broad spectrum of HPV-related diseases. In 2012, NACI updated and strengthened its statement related to the use of HPV vaccines and recommended the use of the quadrivalent HPV vaccine in males between 9 to 26 years of age. A national survey conducted in March 2011 by Ipsos Reid, commissioned by Merck, showed that 85% of parents of males would allow their son to get vaccinated against HPV if it was offered through a publicly-funded program at his school, 88% of parents support the assertion that boys should be vaccinated against HPV in the same program as girls, and 91% of parents agree that vaccinating both boys and girls against HPV would provide greater protection than vaccinating girls alone.

First Canadian Clinic to provide Non-invasive Prenatal Testing (NIPT)

This test can screen for Down syndrome and other chromosome abnormalities as early as 10 weeks into the pregnancy, using a simple blood test. Specifically, Medcan is offering the verifi® prenatal test from Verinata Health®, an Illumina Company. This test analyzes fetal DNA in maternal blood in order to screen for missing or extra copies of chromosomes. The aim of NIPT is to provide the most accurate information available without posing a risk to the pregnancy, in order to minimize unnecessary invasive procedures. Not all NIPT tests are equal. After extensive review of the various NIPT options available, Medcan chose to partner with Verinata Health® to offer the verifi® prenatal test, which represents the most comprehensive non-invasive prenatal test detection menu available. In comparison with other NIPT tests, the verifi® prenatal test offers the option to test for sex chromosome (X and Y) abnormalities in addition to the core set of trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome). Further, the test uses superior technology to provide more accurate information over current prenatal testing methods based on numerical risk scores.

Health Canada approves patch for treatment of Parkinson’s disease

UCB Canada Inc. announced that Health Canada has approved NEUPRO® (rotigotine), the first and only non-ergolinic dopamine agonist available in a patch, to treat the signs and symptoms of idiopathic Parkinson’s disease (PD) and moderateto-severe idiopathic restless legs syndrome (RLS), also known as Willis-Ekbom disease, in adults. NEUPRO® is the first new treatment for Parkinson’s disease approved by HealthCanada in five years and provides 24-hour delivery of rotigotine through the skin into the blood stream. NEUPRO® has demonstrated efficacy in managing motor symptoms associated with Parkinson’s disease. “Parkinson Society Canada is pleased to learn that Canadians living with Parkinson’s now have another treatment option to help manage the symptoms of this chronic disease,” says Joyce Gordon, President and CEO, Parkinson Society Canada. “With innovative therapies such as NEUPRO® and ongoing research into the causes of this disease, we will help to ensure a brighter future and better quality of life for Canadians living with Parkinson’s.” Although the precise mechanisms of action of NEUPRO® as treatment for PD and RLS are unknown, as a PD treatment, the mechanism of action is thought to be related to increasing the activities of the dopamine receptors within the caudate-putamen, the region of the brain that regulates movement. Similarly, in RLS, the mechanism of action of NEUPRO® is thought to be related to its ability to stimulate dopamine receptors.

Canada’s first and only ‘talking’ epinephrine auto-injector

Sanofi Canada announced a new option for the emergency treatment of anaphylaxis. Allerject™ is the first and only ‘talking’ epinephrine auto-injector in Canada. “Sanofi is excited about being able to offer Allerject™,” says Jon Fairest, President and CEO of Sanofi Canada. “Allerject™ is designed to address unmet patient needs and make a positive difference in the lives of those at risk of a severe allergic reaction, and those who care for them.” Although the precise number of people at risk of anaphylaxis is unknown, a recent study found that approximately 7% (or about 2.5 million Canadians) self-report a food allergy. Epinephrine is the drug of choice for the emergency treatment of severe allergic reactions, and is the medicine in the AllerjectTM auto-injector. To help patients and caregivers correctly use the auto-injector, Allerject™ comes equipped with automated voice instructions (in either English or French) which will guide them step-by-step through the injection process in the event of an emergency.Results of Clinical Study of Type 2 Diabetes Drug Candidate A clinical study of peptide TT-401 in type 2 diabetic and obese non-diabetic subjects demonstrated significant improvements in glycemic control and reductions in body weight. This five-week proof of concept study enrolled diabetic patients at five dosing levels and non-diabetic obese patients at one dose level. Both groups received five doses over the five week period and diabetic patients also received stable doses of metformin. The patients who received the three highest doses of TT-401 experienced statistically significant reductions in mean fasting plasma glucose relative to placebo. TT-401 demonstrated an acceptable safety and tolerability profile for all doses, with decreased appetite as the most commonly noted adverse side effect.

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

RevitalAge™ Ultra Supports Youthful Gene Expression

Mitochondrial Renewal

Healthy Aging

Resveratrol supports longevity by enhancing an epigenetic enzyme, SIRT1. It also works in concert with alpha lipoic acid and acetyl-l-carnitine to cooperatively support the synthesis of new mitochondria by promoting healthy activity of another enzyme known as AMP kinase (AMPK), a cellular longevity signal that directs a genetic program of mitochondrial renewal.

Sustained-release CoQ10 provides 24-hour antioxidant protection with complementary support for mitochondrial bioenergetics. Pterostilbene supports healthy activation of PPARα, a genomic receptor involved in cardiometabolic health. †

Under license from

Inc.

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

Your Trusted Source for science-based, hypo-allergenic nutritional supplements.

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

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RevitalAge Ultra ™

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

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

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

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

What Is The Source?

Acetyl-l-carnitine HCl†, alpha lipoic acid (thioctic acid), biotin, resVida® resveratrol and pterostilbene are synthetic. MicroActive® CoQ10-cyclodextrin complex containscoenzyme Q10 obtained naturally from fermentation and potato starch.

PhytoLongevity proprietary blend is sourced from cranberry extract, wild blueberry extract, Orléans strawberry extract and spinach extract.

RevitalAge™ Ultra three vegetable capsules contain

v 00

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

3 capsules daily, with meals. †Under

license from

Inc.

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

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

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calendar JUNE

June 19 Supporting Adrenal Function with Adaptogenic Herbs Organized by: AARM Online Webinar For more information, visit http:// restorativemedicine.org/cme-webinars/ June 25 Uprooting Anxiety: Removing an Obstacle to Sustainable Wellness Organized by: Integrative Therapeutics San Francisco, California For more information, visit http://www.integrativeinc.com/ Education/Events.aspx

July

July 1-3 Internal Medicine in Primary Care Setting Organized by: MCE Conferences Captiva, Florida For more information, visit http://www.mceconferences.com/ medical-conferences.php July 7-9 International Congress on Naturopathic Medicine Organized by: ICNM Paris, France For more information, visit http://icnmcongress.com

Organized by: CIHR Institute of Human Development Toronto, ON For more information, visit http:// www.cihr-irsc.gc.ca/e/45121.html July 17 Promoting Healthy Thyroid Function with Iodine, Bladderwack, Guggul and Iris Organized by: AARM Online Webinar For more information, visit http:// restorativemedicine.org/cme-webinars/ July 22-24 Pediatric and Adult Infectious Diseases: An Evidence-based Approach to Common Problems Organized by: MCE Conferences Anaheim, California For more information, visit http:// www.mceconferences.com/ medical-conferences.php July 26-29 International Academy of Cardiology, Annual Scientific Session Organized by: International Academy of Cardiology Vancouver, British Columbia For more information, visit http:// www.cardiologyonline.com

August

July 10-13 AANP Conference Organized by: AANP Keystone, Colorado For more information, visit http://www.naturopathic.org

August 5 Clinical Topics in Anesthesia Organized by: North West Seminars Banff, Alberta For more information, visit http://northwestseminars.com/ pateintsafety/13patient.html

July 13 Healthy Transformation: Breakthrough Weight Loss Program Organized by: Metagenics Seattle, Washington For more information, please visit: www.metagenics.com

August 6 Novel Nutritional Approaches to Gastrointestinal Disorders Organized by: Metagenics Online Webinar For more information, please visit: www.metagenics.com

July 13-19 9th Annual Summer Institute in Maternal-Fetal and Pediatric Pharmacology Course

September

September 11 Fall Detoxification Teleconference Organized by: Seroyal

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

October

October 4-6 2013 Lifestyle Medicine Summit Organized by: Metagenics Chicago, IL For more information, please visit: www.metagenics.comJuly 17 Promoting Healthy Thyroid Function with Iodine, Bladderwack, Guggul and Iris Organized by: AARM Online Webinar For more information, visit http:// restorativemedicine.org/cme-webinars/ October 5 Advance in women’s Health Organized by: NFH Toronto, Ontario For more information, visit: www.nfh.ca

NOVEMBER

Novemver 16 Advance in women’s Health Organized by: NFH Vancouver, BC For more information, visit: www.nfh.ca

26 www.ihpmagazine.com l June/July 2013

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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

KLEAN Athlete™ Progressive Plant foods play a critical role in our health, but most people don’t get enough. Thanks to PhytoBerry Multi and VegeGreens Multi, it just got a lot easier. They combine to provide the equivalent of all your fruits, all your vegetables and all your vitamins and minerals in just two small scoops.

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

Astaxanthin Powerful antioxidant for the skin, macula, joints, immune system and cardiovascular function. Derived from Haematococcus pluvialis microalgae cultivated under pristine conditions, esterified astaxanthin is a stable, powerful, fatsoluble antioxidant from the carotenoid family. Astaxanthin protects the phospholipid membranes of cells from oxidative damage. Initial trials with astaxanthin suggest that it may boost the skin’s natural antioxidant defenses against free radicals induced by sun exposure. In a human clinical evaluation, supplementation with astaxanthin

PASCOFEMIN® PASCOFEMIN® is a well-tolerated, effective solution for physical and emotional symptoms of menopause such as hot flashes, headaches, mood swings and sleep disturbances. In one study of women who had tried other therapies to control menopause symptoms without success, significant effectiveness was found in 71% of patients. Even more impressive, after patients left the study and had to purchase it on their own, 80% were satisfied enough to continue using PASCOFEMIN®.

There are no known side effects or contraindications.

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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

activrecover+ activrecover+ is designed to target the post activity needs of your workout with all of the nutrients required to recover and repair from a workout. Rebuild - with whey and pea protein isolates, BCAAs and creatine. Re-energize - with carbohydrate sources from orange, glucose and brown rice syrup. Restore - with antioxidant sources from lemon verbana and tart cherry juice.

Metagenics Launches New D3 Liquid Metagenics D3 Liquid features 1000 IU per drop of vitamin D3—the most bioactive form of supplemental vitamin D. Provides vitamin D3 solubilized in oil to support absorption in the intestinal tract. Designed for easy, flexible dosing and supplies about 2275 drops per bottle. Features a pleasant, natural mint flavor for improved patient compliance. Ideal for kids and those who prefer not to swallow tablets or capsules. Metagenics.com | 800 268 6200 Canada

PASCOFLAIR® PASCOFLAIR® is a unique preparation containing 425mg of Passionflower extract. As a widely used herb, Passionflower provides fast and effective relief.

Studies have shown passionflower has anxiolytic effects equal to diazepam, oxazepam, and mexazolam with a better safety profile than these medications. Extracts from passionflower have also shown promise in the treatment of opiate, benzodiazepiwne, 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.

Cyto-Matrix® — Omega-D3 Liquid Forte Evidence based dosages for all indications; High safety profile; Molecularly distilled, ultra-pure fish oil; Easy to administer for maximum patient adherence; No fishy aftertaste, light citrus flavour.

Each teaspoon (5 mls) contains: Fish Oil Concentrate - 4,377 mg; Omega-3 Fatty Acids - 2,845 mg, EPA (Eicosapentaenoic acid) - 1,750 mg; DHA (Docosahexaenoic acid) 875 mg; Vitamin D3 - 1000 IU.

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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

High Dose R-Lipoic Acid Based on recent studies showing that high bolus doses of lipoic acid are effective in blood sugar maintenance, AOR’s High Dose R-Lipoic Acid offers 95% pure R-lipoic acid, which is more effective than regular alpha-lipoic acid. Lipoic acid also helps protect the nerves and tissues from sugar damage.

Krill Oil Genestra brand 100% pure krill oil carries omega-3s in phospholipid form – the building blocks that help regulate cellular transport and aid cell membrane protection by facilitating fatty acid delivery to the cells. The unique 2-piece hard shell caplique technology minimizes krill oil sensitivity to heat and humidity while reducing oxidation potential which in turn, limits odour, eliminates fishy aftertaste and reduces reflux.

NFH’s Energy Smart A blend of MCT oil and plant sterols designed to help endurance athletes. This combination will assist athletes with prolonged endurance during their sport as well as assisting with enhancing recovery and supporting immune function. The synergistic benefits of medium-chain triglycerides and phytosterols in combination promote optimal metabolism including increased beta-oxidation, cholesterol-lowering action, antioxidant capacity, and anti-inflammatory action, and may be applied to promote cardiovascular health and lipid management, weight management, athletic performance, and recovery.

Bio-K

NFH’s NAC SAP NAC is a glutathione precursor which supports the body’s natural ability to quench free radicals. It can also be useful as part of a detoxification program.

NAC also has the ability to help thin mucus secretions and can be very effective for assisting in the treatment of chest infections.

Your Ideal travelling companion!

Bio-K+® Travel Protect probiotic is your ideal travel companion and your first line of defense to ensure a holiday without unpleasant surprises! Each capsule contains 30 billion probiotic bacteria and comes in a convenient travel size package. It is your natural solution for protecting your digestive system from harmful bacteria caused by contaminated food, water and ice. biokplus.com | 1 800-593-2465

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

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

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

Supplied Bio-K+® guaranties a minimum of 50×109 L. acidophilus CL1285® and L. casei LBC80R® per capsule at expiration date. These bacteria are live and protected with an enteric coating. Lyophilized bacteria are the result of fermentation, concentration and freeze-dry processes.

A mixture containing a predetermined concentration of lyophilized bacteria, cellulose, ascorbic acid, and magnesium stearate is prepared. This mixture is then added in a vegetable cellulose capsule pigmented with colloidal silicone dioxide. Then, the capsule is enteric coated. Each capsule contains: ≥50×109 live strains of L. acidophilus CL1285® and L. casei LBC80R®. Nonmedicinal ingredients: ascorbic acid, cellulose, ethylcellulose, hypromellose, magnesium stearate, medium chain triglycerides, silicone dioxide, sodium alginate and titanium dioxide. Bottles of 15 or 250. A box contains 10 or 100 groups of 10, individually wrapped capsules in blister aluminumsealed sheets. Refrigerate at 4°C for maximum activity.

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(100 Billion bacteria)

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

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

Precautions Bio-K+® capsules should be swallowed whole. To preserve the enteric coating properties, do not chew, crush or open the capsules.

It is safe to take Bio-K+® capsules for a prolonged period of time.

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

Dosage Recommended Dosage During Antibiotic Therapy • 2 capsules per day for the duration of the antibiotic treatment, and for five days after the treatment is completed.

• The capsule should be taken at least two hours after antibiotic administration.

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cover story

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cover story

Farid Wassef,

BSc Pharm, RPh Bridging the gap

By Philip Rouchotas MSc, ND â&#x20AC;˘ Photography by John Milios

Farid Wassef is a second generation pharmacist born and raised in the Stouffville, Ontario area. The pharmacy was first opened by Faridâ&#x20AC;&#x2122;s father in 1974, which Farid undertook management of in 1989. In 2006, Farid felt it appropriate to merge with the local IGA pharmacy team, and has been partnered with them since. Farid tells a tale that is familiar to IHP readers, of an interest in something other than conventional medicine from an early stage of training, his personal interest leading him to seminars hosted by the likes of Wright and Gaby, and culminating in the decision to offer services of integrative medicine very early on in his career. The very unique twist to this story is that Farid is offering these services as a pharmacist, not the designation(s) we are accustomed to as a provider of integrative medicine.

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cover story

Farid Wassef is a second generation pharmacist who has worked and lived in Stouffville, Ontario for over 40 years. The family pharmacy was owned by Farid’s father Lou in 1974, which Farid took over in 1989 upon graduation. In 1993, Farid opened a patient consultation practice, which involved integrating lifestyle changes, nutrition, and natural health products with pharmaceutical care. In 2006, Farid merged his pharmacy with his colleague’s at Stouffville IDA Pharmacy, where Farid continues to practice integrative medicine. Farid graduated from the prestigious Massachusetts College of Pharmacy in 1989 and quickly undertook the role of management of the family pharmacy.

By 1993, Farid had built an office within the pharmacy and was actively seeing patients.

“I was very frustrated by a model that only allowed a couple of minutes to interact with a patient at the pharmacy counter” describes Farid. “That doesn’t provide the

opportunity for any sort of counselling whatsoever!”

It was surprising to hear this familiar story from a pharmacist! I was personally unaware of how a pharmacist would justify the practice of integrative medicine under the license of a pharmacist... Farid was eager to clarify.

“Within the scope of practice of pharmacy, a pharmacist is permitted to counsel on prevention and treatment of disease, counsel on diet, lifestyle, nutritional/ nutraceutical supplements, botanical medicines, and of course pharmaceutical drugs. While a pharmacist may not be permitted the act of diagnosis, I found many MD’s in the Stouffville and surrounding area eager to collaborate with an objective and evidence- based person providing good information on natural medicines. Through these collaborations we were able to offer patients a broad array of integrative diagnostic techniques in addition to standard laboratory procedures.”

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Farid was not satisfied with his role as pharmacist and practitioner... He was driven to spread the word to other pharmacists, MD’s, and anyone else who would listen as to the power of diet and lifestyle in health promotion, disease prevention, and disease treatment, and eager to educate his fellow pharmacists as to the role they can and should be playing in their patients care. Working with the Institute of Functional Medicine (whom Farid credits with providing most of the training he relies upon as a practitioner of integrative medicine), Farid created a continuing education curriculum for pharmacists to receive training in integrative medicine. He has likewise lectured across North America to predominantly pharmacists and MD’s regarding application of integrative medicine, and methods through which integrative minded pharmacists can successfully collaborate with MD’s in their community.

His immense efforts to move the discipline of integrative medicine forward earned him the 2006 award for Canadian Pharmacist of the Year.

While juggling the roles of a pharmacy manager, seeing 80+ patients per week, authoring over 200 articles, CE courses, and books (including Breaking the Age Barrier – Strategies for Optimal Health, Longevity, and Energy published

by Penguin in 2003), and his ongoing industry consulting and speaking engagements, yet another intriguing path caught Farid’s eye; politics. The idea of impacting healthcare from a “top down” approach made a lot of sense to him! Farid slowly moulded his career to be able to take on the workload politics would entail; he sold ownership of the pharmacy and merged with the local IDA team, where he maintains an office and his practice to this day... He cut back on time with patients, yet maintains an important practice within the Stouffville IDA pharmacy, and continues to welcome public speaking arrangements, although at a reduced rate than in the past.

It was 2009 when Farid first actively participated in a political role, attempting to block proposed cuts to the healthcare system (that subsequently came into effect in 2010). The final straw that brought Farid to action was the interpretation that the $1.2 billion e-health scandal is what necessitated healthcare cuts in the first place!

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From left to right: Rob, Donna, Joyce, Farid, Kathy, Dianne.

The PC party of Ontario approached Farid in 2010 after witnessing his passion and determination to effect change, and in 2011 he secured his nomination as the PC candidate for the riding of Stouffville, Markham, Richmond Hill, and King townships. He lost the 2011 election to the incumbent Liberal candidate. Farid Wassef has been re-nominated and will stand in the next general election as the PC Candidate

“I was very frustrated by a model that only allowed a couple of minutes to interact with a patient at the pharmacy counter” of Oak Ridges-Markham for Member of Provincial Parliament. Farid is determined to improve our healthcare system, which he believes should focus more on disease prevention and extending an individual’s functional health span.

It was a special experience to visit the Stouffville IDA where Farid continues to base himself and see patients. The pharmacy

runs as any conventional pharmacy can be expected to run, yet adjacent to where the pharmacists operate is a segregated office area where Farid conducts patient visits.

In the absence of Farid’s influence over the years, the pharmacy team likely would have little to zero interest in integrative medicine. Yet through years of observation of Farid’s practice, the entire pharmacy team at Stouffville IDA has a unique, welldeveloped, intrigue/ interest in the role of integrative medicine in today’s healthcare system. Also of tremendous interest were the unique offerings of natural health products by the pharmacy. Brands not typically associated with pharmacy were made available for the public, clearly guided

by Farid over the years yet managed by the conventionally practicing pharmacists of the facility. Also, and near to my heart, the current owner of the facility is a fan of history of medicine. His pharmacy is lined with paraphernalia and artifacts from generations of pharmacists, including tincture bottles that must be over 100 years old, historical instruments of the profession, and photos of a graduating class of pharmacists from the very early 1900’s.

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cover story

Apparently the individual who founded the first ever pharmacy in Stouffville is pictured in the photo.

IHP is grateful to Farid Wasef and the entire Stouffville IDA team for taking the time to allow us to showcase their efforts to you. Farid may not have the expected credentials of a practitioner of integrative medicine, yet he delivers the service at a level equal to and beyond that of anyone in the field. Like so many professionals IHP has had the privilege of showcasing, the practice of integrative medicine begins, grows, and thrives through one common seed; passion! Passion to help others, to solve mysteries common- place answers simply donâ&#x20AC;&#x2122;t make sense for, and ultimately to achieve maximal positive impact for people using the least invasive strategy available. Farid has educated thousands of healthcare providers in this area. He has now turned his attention to the political arena, in hopes of bringing further change through legislation, hopeful the clinical aspect of thing resides in good hands.

We wish you much success Farid in helping to bring healthcare reform we at IHP agree is desperately required. â&#x2013;

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L-Glutamine SAP

Science-based amino acid for gastrointestinal and immune health l-Glutamine

is the most abundant amino acid in the human body.(1) Glutamine is metabolized in the small intestine and serves as an important fuel source for intestinal mucosa.(2) Glutamine plays an important protective role in the intestinal tract, and is crucial for patients with increased permeability of the intestinal system, which can be seen in patients with inflammatory bowel diseases—including for example Crohn’s disease or ulcerative colitis—, as well as in irritable bowel syndrome and allergies.(3, 4) This amino acid plays an important role in nutrient metabolism, the immune system, protein turnover, and acid/base balance.(1) With infection, severe burns, cancers, and some other pathologies, both intracellular and extracellular concentrations of glutamine are markedly reduced.(1) This leads us to believe that glutamine supplementation may play an important role in the body’s ability to recover from illness. Glutamine has also been studied for use in patients after gastric surgery and may act as a motility-recovery agent after gastrectomy.(5) Patients receiving treatment for cancer often experience malnutrition and cachexia, which may be improved with glutamine supplementation.(6)

ACTIVE INGREDIENTS

Each bottle contains: l-Glutamine

(powder) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300 g

Contains no: Preservatives, allergens, artificial flavor or color, sweeteners, wheat, gluten, soy, starch, yeast, citrus, egg or dairy.

L-Glutamine SAP contains 60 servings of 5 g per bottle

DOSAGE

Adults: Take 1 scoop once or twice daily mixed with juice or water or as directed by your health care practitioner.

INDICATION

ɶ L-Glutamine SAP can be used to protect and heal a permeable intestinal tract. ɶ L-Glutamine SAP can help reduce inflammation in the intestinal tract and therefore help treat IBD and IBS. ɶ L-Glutamine SAP may be beneficial to enhance recovery from acute illnesses or infections and severe burns. ɶ L-Glutamine SAP may provide ergogenic benefit to endurance athletes by increasing time to exhaustion. ɶ L-Glutamine SAP could be helpful in preventing postoperative ileus after gastrointestinal surgery. ɶ L-Glutamine SAP may help treat and prevent cachexia and malnutrition in patients undergoing cancer treatment.

SAFETY

l-Glutamine is generally considered safe with the no-observed-adverse-effect level

determined to be 5.0% l-glutamine in the diet, which was around 4000 mg/kg.(7)

PURITY, CLEANLINESS AND STABILITY

Third-party testing is performed on finished product to ensure L-Glutamine 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

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IHP 2013

16:28:52

L-Glutamine SAP PRODUCT MONOGRAPH

l-GLUTAMINE

AND INFLAMMATION

L-Glutamine administration has been shown in recent studies to enhance heat shock protein (HSP) expression, which may be the key to its mechanism of action with regards to its protective ability.(4) In a study performed on rats which were induced with colitis, animals were administered either 0.75 g/kg/d glutamine or a placebo for 7 d. After 7 d, a reduction was observed in bleeding and diarrhea in the treatment group compared to placebo, concomitant with increases in levels of both Hsp25 and Hsp70.(4) Researchers concluded that glutamine is crucial for colonic epithelium to mount a cell-protective, antiapoptotic and anti-inflammatory response against inflammatory injury.(4) l-GLUTAMINE

AND POSTOPERATIVE ILEUS

l-GLUTAMINE

AND ONCOLOGY

One of the most common complications of gastrointestinal surgery is postoperative ileus (POI).(5) In a study conducted on patients after a partial distal gastrectomy for gastric cancer, patients were split into two groups and received either glutamine at 3 g/d or placebo.(5) Results were based on manometric recordings done 12 d after surgery. Motor activity in the duodenum of the glutamine group was significantly greater than that of the control group.(5) Phase-3 motor activity (interdigestive migrating motor contractions) in the glutamine group was rated at 60%, versus 19% in the control group.(5) This study indicates that glutamine can function as a motility-recovery agent after gastrectomy.(5) For patients with cancer, malnutrition is associated with a poor prognosis, and weight loss can be a very important predictor of mortality.(6) Patients supplementing with glutamine saw benefit, including a reduction in tissue toxicity and improved outcomes, while supporting the efficacy of the chemotherapy treatments.(6) In a study looking at 50 GI cancer patients who had undergone surgery and received total parenteral nutrition (TPN) after surgery, researchers explored the inflammatory modulation effect of glutamine supplementation in one half of the patients.(8) The supplemented group showed a reduction in interleukin-6 (IL6) and serum C-reactive protein, and had higher serum prealbumin levels, as well as better nitrogen balance than the control group.(8) The control group had 4 cases of postoperative infections, while none were reported in the treatment group.(8) Researchers concluded that enriching TPN with glutamine may be beneficial in reducing inflammation and decreasing morbidity associated with infections in postoperative GI cancer patients.(8) l-GLUTAMINE

AND INFLAMMATORY BOWEL DISEASE/ IRRITABLE BOWEL SYNDROME

The pathophysiology of irritable bowel syndrome (IBS) is not well understood, but one pathway that may be involved is that of increased intestinal permeability.(3) Researchers performed a controlled study on patients with diarrhea-predominant IBS and assessed their intestinal membrane permeability using the lactulose/mannitol test as well as looking at the glutamine synthetase expression in gut tissue.(3) A subset of 42% of patients had both increased intestinal membrane permeability and decreased glutamine synthetase expression compared to the controls and IBS patients with normal membrane permeability.(3) This result indicates that certain patients with IBS who have increased membrane permeability as well as decreased glutamine synthetase expression may benefit from supplemental glutamine in the diet.

A study performed in rats looked at the benefit of prophylactic administrations of glutamine for its capability to stop inflammatory damage.(9) Researchers found that administration of glutamine before induction of colitis resulted in decreased indices of inflammation;

For more information visit: www.nfh.ca

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however, this same benefit was not seen if administered at the same time as the colitis was induced.(9) Further study needs to be performed on human subjects but it may be promising in that glutamine could be useful for patients with colitis in remission to help prevent flare-ups. l-GLUTAMINE

AND ENDURANCE ATHLETES

l-GLUTAMINE

AND SEVERE BURNS

Endurance athletes often become mildly dehydrated during the course of training and competition. Researchers exploring the effects of l-alanyl-l-glutamine ingestion during performance measured changes in fluid regulations; immune, inflammatory, as well as oxidative stress; and recovery in athletes who were properly hydrated and during dehydration.(10) Across four groups of athletes tested, group 1 did not rehydrate, group 2 rehydrated using only water, group 3 rehydrated using water and 0.05 g/kg of the supplement, and group 4 rehydrated using water and 0.2 g/kg of the supplement.(10) Subjects then worked at 75% of their VO2 max on a cycle ergometer. Blood samples were obtained immediately following the exercise and after resting for 24 h.(10) Results demonstrated that athletes in groups 3 and 4 had significantly greater times to exhaustion than those in groups 1 and 2, as well as having lower aldosterone levels and higher plasma sodium levels.(10) Group 4, who received the largest amount of glutamine, demonstrated the greatest improvement.(10) Researchers concluded that the supplementation provided a significant ergogenic benefit to athletes by increasing the time to exhaustion during mild dehydration.(10) A clinical study was performed exploring the protective effects of oral supplementation of glutamine on intestinal mucosal barrier function in patients with severe burns.(2) Patients were randomly divided into two groups and received either placebo or glutamine granules 0.5 mg/kg orally for 14 d.(2) Results showed that the glutamine group compared to the control group had a lower urinary lactulose/mannitol ratio, improved wound healing, and shorter hospital stays of 46.6 d on average, versus 55.7 d on average in the control group.(2) This study demonstrates that oral glutamine could reduce the amount of intestinal injury and permeability as well as improve wound healing, leading to shortened hospital stays.(2)

SAFETY

l-Glutamine

is a safely administered conditional essential amino acid.

Safety studies have demonstrated that l-glutamine can make up 5% of the total dietary intake with no adverse effects noted.(7)

REFERENCES 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

Xi, P., et al. “Regulation of protein metabolism by glutamine: implications for nutrition and health”. Frontiers in Bioscience 1, No. 16, January 2011: 578–597.

Peng, X., et al. “Effects of enteral supplementation with glutamine granules on intestinal mucosal barrier function in severe burned patients”. Burns 30, No. 2, March 2004: 135–139.

Zhou, Q., et al. “MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome”. Gut 59, No. 6, June 2010: 775–784.

Xue, H., A.J. Sufit, and P.E. Wischmeyer. “Glutamine therapy improves outcome of in vitro and in vivo experimental colitis models”. Journal of parenteral and enteral nutrition 35, No. 2, March 2011: 188–197.

Mochiki, E., et al. “Effects of glutamine on gastrointestinal motor activity in patients following gastric surgery”. World journal of surgery 35, No. 4, April 2011: 805–810.

Paccagnella, A., I. Morassutti, and G. Rosti. “Nutritional intervention for improving treatment tolerance in cancer patients”. Current Opinion in Oncology 23, No. 4 (2011): 322–330.

Wong, A.W., et al. “Oral subchronic and genotoxicity studies conducted with the amino acid, l-glutamine”. Food and chemical toxicology 49, No. 9 (2011): 2096–2102.

Lu, C.Y., et al. “The inflammatory modulation effect of glutamine-enriched total parenteral nutrition in postoperative gastrointestinal cancer patients”. The American surgeon 77, No. 1, January 2011: 59–64.

Israeli, E., et al. “Prophylactic administration of topical glutamine enhances the capability of the rat colon to resist inflammatory damage”. Digestive diseases and sciences 49, No. 10, October 2004: 1705–1712.

Hoffman, J.R., et al. “Examination of the efficacy of acute l-alanyl-l-glutamine ingestion during hydration stress in endurance exercise”. Journal of the International Society of Sports Nutrition 7, No. 1, 2010 February 3: 8–19. © NFH Nutritional Fundamentals for Health 2012

2013-05-17 16:28:52 13-06-07 5:02 PM

clinic profile

From left to right, Sheryl Hoo MA, DO; Vivianne Bentley PhD, OPQ; Mark MacNeil CST; Ilana Block BSc, ND; Orna Villazan BSc, ND; Isabelle Richter DO; Valerie Namer MD, DO

Harmony Health Centre

By Chris Habib, ND â&#x20AC;˘ Photography by Michael Perl

W

e at IHP are pleased to introduce the Harmony Health Centre, a beautiful multi-disciplinary clinic providing high-quality alternative healthcare options. Harmony Health Centre is located in Westmount, Quebec, where Naturopathic Doctors are not currently regulated. As a result, they have faced unique challenges and have developed creative solutions to work with their community. The clinic is run by two experienced Naturopathic Doctors, Ilana Block, ND and Orna Villazan, ND. Dr. Block and Dr. Villazan met in 2005 and together founded Harmony Health Centre with the dream of providing excellent patient care. They

have a general family practice, and they see a lot of gastrointestinal concerns, weight concerns, womenâ&#x20AC;&#x2122;s health and fertility, and mental health concerns. These talented doctors are now managing one of the few integrative clinics in Quebec!

The clinic has a storefront location and the zen atmosphere helps to relieve stress from the moment patients walk in.

The facility has four beautiful treatment rooms and each ND sees over 20 patient visits per week. All of the clinic operations were developed with the patient experience as the top priority, where patients can come in early, have a tea, read, relax, and if desired, see a couple of practitioners on the same day.

The clinic embodies a holistic health-

promoting environment. The majority of the practitioners at the clinic are fluent in both French and English. The clinic has extended hours in evenings and on weekends (they are open seven days a week) and they are fully accessible by public transit. The marketing strategies they use include a strong online presence through their website and Facebook, and local information sessions they host for the public.

Dr. Block and Dr. Villazan were trained and are licensed in the province of Ontario (as out of province practitioners). In Quebec, there are no regulations for naturopathic medicine and without regulation, the scope of practice of Naturopathic Doctors can be quite limited. Naturopathic Medicine is currently very confusing for the average person seeking care, which makes educating the public challenging, but imperative. In Quebec, there are numerous challenges that NDs in regulated provinces do not face. From our understanding, there are no laws overseeing the practice of naturopathic medicine, including a description or

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clinic profile regulation for what NDs are able to do. As a result, NDs, like other unregulated practitioners, are faced with the concept that they canâ&#x20AC;&#x2122;t practice what is considered medicine without a license. If you are not licensed as a medical doctor, you are limited in your practice of medicine. For example, the NDs do not have the authority to make a diagnosis, to perform venipuncture

or intramuscular injections, to perform gynecological exams, or to perform acupuncture. As a result, the services and care that these doctors are able to provide has to be of utmost quality to balance out the regulatory limitations.

They work together as a team, provide holistic care, and inter-refer to other health care practitioners.

Another limitation these NDs face is

that there are approximately 5500 individuals practicing as natural therapists in Quebec. There are currently 15 Naturopathic Doctors in the province who are licensed from a regulated jurisdiction.

Insurance companies do not make a distinction between licensed NDs and those who have done a few weekend courses.

Since 1992, the QANM (Quebec Association of Naturopathic Medicine) has been working on behalf of the profession, attempting to get a law in place that would protect and recognize a full scope of practice for the ND as well as protecting the public. Without over-stepping their bounds or stepping on anyoneâ&#x20AC;&#x2122;s toes, Dr. Block and Dr. Villazan have developed functioning relationships with many medical doctors and other health practitioners. This has helped them overcome some of the regulatory limitations by utilizing these other practitioners as part of their referral base, thus allowing their patients to access the care they need.

Most of the patients at the clinic come from word-of-mouth referrals. Patients see any practitioner that they originate contact with and then usually get referred appropriately to other practitioners. The other opportunity that patients have to

April/May 2013 l www.ihpmagazine.com 41

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clinic profile meet other practitioners come from group workshops that are conducted at the clinic, including workshops in women’s care or a versatile session called “Conversations on Health,” where multiple practitioners discuss pain management, stress relief, depression, anxiety, and other conditions. These sessions are free to the public. The clinic also sees many referrals from outside the clinic, including from integrative medical doctors, personal trainers, and others such as psychologists.

Harmony Health Centre carries numerous reputable brands in their dispensary, including AOR, Metagenics, Seroyal, NFH, NaturePharm, St-Francis Herb Farm, and Vitazan. They carry

tinctures from Mediherb and St-Francis and homeopathics from UNDA, Boiron, Pascoe, and Heel. They utilize labs from Gamma-Dynacare, Genova, Metametrics, Doctor’s Data, and Rocky Mountain Analytical. Based on their patient base, the most commonly run labs are food sensitivity tests, parasitology or digestive analysis, and heavy metal testing.

When asked what messages they would like to provide for other doctors, Dr. Block says: “Come to Quebec! The more NDs there are, the better it will be. Despite the challenges, there is an exciting shift occurring in integrative medicine in the province.” Harmony Health Centre is a dynamic work

environment and they are always looking to add new members to their team. Both Dr. Block and Dr. Villazan believe there is a strong need to increase the number of NDs in Quebec to better offer quality health care options to Quebecers as well as to obtain more visibility and public awareness. ■

CLINIC TEAM Ilana Block BSc, ND - Naturopathic Doctor

Sheryl Hoo, MA, DO – Osteopath

Orna Villazan BSc, ND - Naturopathic Doctor

Susan Lazar Hart CFMW - Life Coach and Counsellor

Vivianne Bentley PhD, OPQ - Integrative Psychologist

Maura Fishman MSW - Social Worker and Counsellor

Valérie Namer, MD, DO – Osteopath

Lesley Mandy Rubinoff CNP, NNCP - Holistic Nutritionist

Isabelle Richter DO – Osteopath

Mark MacNeil CST - CranioSacral Therapist

42 www.ihpmagazine.com l April/May 2013

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TM

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

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PRODUCT mOnOgRaPh

PRODUCT MONOGRAPH OIL OF OREGANO

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

Human studies

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

Animal and In vitro studies

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

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

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

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

Toxicology

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

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

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

References

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

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

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

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

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

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

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

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

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

2006;69(2):369-75.

Uyanoglu M, Canbed M, Aral E, Husnu Can Baser K. Effects of carvacrol upon the liver of rats undergoing partial hepatectomy. Phytomedicine 2008; 15(3): 226-9. ihpSept10_NAHS_Ad.indd 2 058.IHP NAHS mono.indd 1 IHPAPR2012_10055_North_American_Herb_and_Spice_FP2.indd 2

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The Journal of

1

1

56

p

2

2

62

3

3

CE

Sports Nutrition

In the context of lifestyle medicine

by Eva M Selhub, MD and Alan C Logan, ND

68

p

Autoimmunity and Bone Health

by Heidi Fritz, MA, ND Research Fellow, Canadian College of Naturopathic Medicine Bolton Naturopathic Clinic, 64 King St W, Bolton, Ontario, L7E1C7

p

D HEA Part II

Insomnia

Role for acupuncture and melatonin

by Rochelle Fernandes MSc, ND (cand)

RD Research Consult, 231 Fort York Blvd, Suite 2607, Toronto, ON M5V 1B2

CE p72 Effectiveness of Intravenous Vitamin C

in Combination with Conventional Chemotherapy in Cancer Treatment

A Review

by James Bao, Chloe Haldane, Yvonne Lee, Brian Li, Olesya Petrenko, Christopher Wang,

Wendy Zhou, Jordan Robertson ND

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editor’s letter

In Memoriam

I

t is with tremendous sadness and a heavy heart that we announce the sudden passing of Roger Brumback, an esteemed and valued member of the IHP Editorial Board. Roger was a fixture at the annual American Association of Naturopathic Physicians (AANP) symposium, applying his discerning and critical eye to the profession of naturopathy while embracing an intense interest and respect for the role of a patient- centred medical model in modern healthcare.

Roger’s roles as Professor of Pathology at the Creighton University School of Medicine, Editor-in-Chief of the Journal of Child Neurology, and the Journal of Evidence- Based Complementary and Alternative Medicine provided him a unique and welcomed lens through which to evaluate the practice of integrative medicine.

I met Roger six years ago at an AANP convention. He was sitting down, taking a break between conference talks. I approached him assuming him to be a senior ND. Within minutes we were engaged in a wonderfully intense discussion of the evidence- base concerning mainstream psychiatry; he provided me 10 citations for each one I could mention, yet kept probing me to see how far down the rabbit hole I could go regarding published evidence of naturopathic medicine for management of psychiatric concerns. I eagerly anticipate my annual reunion with Roger at the AANP convention; I never had a conversation with him that didn’t end up in topic ideas, emailing of full-text articles, etc... I don’t think the AANP experience will ever feel the same to me moving forward.

While IHP retains an almost exclusively Canadian focus, it was an obvious fit to invite Roger to join our Editorial Board. And true to form, he had an immediate positive impact on the direction and overall rigor of the publication. IHP, and the entire discipline of integrative medicine, miss you Roger. We wish the entire Brumback family our heartfelt sympathies and best wishes.

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

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section header

Publisher | Sanjiv Jagota (416) 203-7900 ext 6125 Editor-in-Chief | Philip Rouchotas, MSc, ND (416) 203-7900 ext. 6109 Associate Editor | Christopher Habib, ND Art Director | Malcolm Brown Production Manager | Erin Booth (416) 203-7900 ext. 6110 Contributors Heidi Fritz, MA, ND, Eva M. Selhub, MD, Alan C. Logan, ND, James Bao, BSc, Chloe Haldane, BSc, Yvonne Lee, BSc (Cand), Brian Li, BSc, Olesya Petrenko, BSc, Christopher Wang, BSc, Wendy Zhou, BSc (Cand), Jordan Robertson, ND, Rochelle Fernandes, MSc, ND (Cand), Christopher Habib, ND, Philip Rouchotas, MSc, ND

President | Olivier Felicio (416) 203-7900 ext. 6107 CEO | Cory Boiselle (416) 203-7900 ext. 6114 Controller & Operations | Melanie Seth CMO | Zinnia Crawford (416) 203-7900 ext. 6135 Advertising Information Sanjiv Jagota | Tel: (416) 203-7900 ext 6125 Email: sanjiv@ihpmagazine.com Paul Airut | Tel: (416) 203-7900 ext 6103 Email: paul@gorgmgo.com Jeff Yamaguchi | Tel: (416) 203-7900 ext 6122 Email: jeff@gorgmgo.com Jason Cawley | Tel: (416) 203-7900 ext 6134 Email: jason@gorgmgo.com Erin Poredos | Tel: (416) 203-7900 ext 6128 Email: erin@gorgmgo.com Circulation Garth Atkinson | Publication Partners 345 Kingston Rd., Suite 101 Pickering, Ontario, L1V 1A1 Telephone: 1-877-547-2246 Fax: 905-509-0735 Email: ihp@publicationpartners.com

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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.

June/July 2013 l www.ihpmagazine.com 47

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METAGENICS ESTROVERA™ 80026945 Estrovera by Metagenics features a special extract of Siberian rhubarb root (Rheum rhaponticum) designed to reduce hot flashes and other menopausal symptoms without potential serious adverse events associated with conventional hormone therapies (HT).

Menopause is the clinical term used after menstruation has ceased for one year, after which women are considered postmenopausal [1]. In the Western world, the age range for natural menopause is 40 to 58 years, with 51 being the median age for menopause. The average age of menopause in Canada is also 51, and it is estimated that women over age 50 will comprise almost one quarter (22%) of the population by the year 2026 [2]. Of all the menopausal symptoms, hot flashes (also referred to as hot flushes) are the most common and potentially debilitating. Nearly 80% of women in Western countries suffer from hot flashes, with 30% reporting hot flashes severe and frequent enough to seriously affect quality of life [3].

HT is considered the most effective medical treatment option for relief of hot flashes and other menopausal symptoms [4]. However, HT is currently recommended only for moderate to severe vasomotor symptoms due to potential increased risk of breast cancer, cardiovascular events and other unwanted side effects [1]. The North American Menopause Society recommends using the lowest possible dose for the shortest duration possible [3]. The Society for Obstetricians and Gynaegologists of Canada also recommends using the lowest effective dose for HT [2]. Women with a history of cardiovascular events, venous thromboembolism, breast or uterine cancer, or liver disease, should not use estrogen to alleviate vasomotor symptoms [1].

Among the natural non-pharmalogical therapies, phytoestrogens are the most popular and the most studied category. Phytoestrogens are plant substances found in soy, red clover, flax, hops, and others, that possess weak estrogenic activity by binding to estrogen receptors (ER). However, systematic review of literature found that phytoestrogens such as isoflavones, lignans, and 8-prenylnaringenin have, at best, only modest effect in ameliorating menopausal symptoms [5-7].

Since 1993, a special phytoestrogen extract from the root of Siberian rhubarb (Rheum rhaponticum) known in scientific literature as ERr 731™ has been recommended by healthcare practitioners in Germany for menopausal hot flashes and related complaints [8]. Unlike Chinese rhubarb (e.g., R. palmatum, R. officinale) or other medicinal rhubarb species that contain strong laxatives anthraquinones, the main constituents of ERr 731 are hydroxystilbenes, including rhaponticin, desoxyrhaponticin, rhapontigenin, and desoxyrhapontigenin [8]. They are found to be agonists of estrogen receptor β (ERβ) and do not display ERα activity in endometrial tissue in laboratory studies [9]. ERβ activation is involved in the estradiol-mediated reduction of hot flashes [10]. In tissues that express both ERα and ERβ, ERβ acts as a negative regulator of ERα and offers protection against ERα-mediated effects in the breast and endometrium [11, 12].

Clinical trials have demonstrated that 1 tablet (4 mg) daily of ERr 731 offers effective relief for common menopausal symptoms, including hot flashes [8, 10, 1315]. For example, in a multicenter, randomized, placebo-controlled clinical trial in which 112 perimenopausal women with menopausal symptoms received either 1 tablet of ERr 731 (n=56) or placebo (n=56) for 12 weeks, ERr 731 treatment compared with placebo treatment resulted in [15]: • A significant reduction of the Menopause Rating Scale (MRS) total score and in each individual MRS item score • A significant reduction in the number of hot flashes, from an average of 12 per day at baseline to 2.8 ±2.8 (mean ± SE) per day at 12 weeks • A significant reduction in the hot flash weekly weighted score In a long-term clinical study with subjects taking ERr 731 for up to 24 months, women reported continued symptom reduction to help improve quality of life through reduced anxiety, negative mood, and sleep disturbances [10].

Data from these clinical trials also show that ERr 731 is well tolerated; no ERr 731-related adverse events are observed. [8, 10, 13-15] ERr 731, the active ingredient in Estrovera, is available to healthcare practitioners in North America, exclusively from Metagenics, Inc. 6.

Estrovera ingredients (per 1 tablet) Medicinal ingredient: Rhapontic Rhubarb (rheum rhaponticum root) ERr 731 Non-Medicina ingredients: Microcrystalline cellulose, stearic acid (vegetable), croscarmellose sodium, silica, and enteric coating (deionized water, cellulose acetate phthalate, glycerol triacetate, ammonium hydroxide, hypromellose, maltodextrin, and polyethylene glycol).

4 mg

7.

8.

9.

10.

References 1.

2.

3.

4.

5.

Nelson HD. Menopause. Lancet. 2008;371(9614):760770.

Society of Obstetricians and Gynaecologists of Canada.

Canadian Consensus Conference on Menopause, 2006 Update. J Obstet Gynaecol Can. 2006;28:S1-S112.

Umland EM. Treatment strategies for reducing the burden of menopause-associated vasomotor symptoms. J Manag Care Pharm. 2008;14(3 Suppl):14-19.

North American Menopause Society. The 2012 hormone therapy position statement of: The North American Menopause Society. Menopause. 2012;19(3):257-271.

Coon JT, et al. Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis. Phytomedicine. 2007;14(2-3):153159.

IHPAPR2012_XXXX_ADVERTISER_Product_FP.indd 2

11.

12.

13.

14.

15.

Lethaby AE, et al. Phytoestrogens for vasomotor menopausal symptoms.

Cochrane Database Syst Rev. 2007;(4):CD001395.

Clarkson TB, et al. The role of soy isoflavones in menopausal health: report of The North American Menopause Society/Wulf H. Utian Translational Science Symposium in Chicago, IL (October 2010). Menopause. 2011;18:732-753.

Heger M, et al. Efficacy and safety of a special extract of Rheum rhaponticum (ERr 731) in perimenopausal women with climacteric complaints: a 12-week randomized, double-blind, placebo-controlled trial. Menopause.

2006;13(5):744-759.

Wober J, et al. Activation of estrogen receptor-beta by a special extract of Rheum rhaponticum (ERr 731), its aglycones and structurally related compounds. J Steroid Biochem Mol Biol. 2007;107(3-5):191-201.

Hasper I, et al. Long-term efficacy and safety of the special extract ERr 731 of Rheum rhaponticum in perimenopausal women with menopausal symptoms.

Menopause. 2009;16(1):117-131.

Frasor J, et al. Response-specific and ligand dose-dependent modulation of estrogen receptor (ER) alpha activity by ERbeta in the uterus. Endocrinology.

2003;144(7):3159-3166.

Lindberg MK, et al. Estrogen receptor (ER)-beta reduces ERalpha-regulated gene transcription, supporting a "ying yang" relationship between ERalpha and ERbeta in mice. Mol Endocrinol. 2003;17(2):203-208.

Kaszkin-Bettag M, et al. Efficacy of the special extract ERr 731 from rhapontic rhubarb for menopausal complaints: a 6-month open observational study. Altern Ther Health Med. 2008;14(6):32-38.

Kaszkin-Bettag M, et al. The special extract ERr 731 of the roots of Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women. Menopause. 2007;14(2):270-283.

Kaszkin-Bettag M, et al. Confirmation of the efficacy of ERr 731 in perimenopausal women with menopausal symptoms. Altern Ther Health Med. 2009;15(1):24-34.

13-06-10 9:41 AM

peer review

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

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

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

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

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

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

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

David W Lescheid, BSc, PhD, ND Lichtentaler Strasse 48 76530 Baden-Baden, Germany 20davidl20@gmail.com

Heidi Fritz, MA, ND Bolton Naturopathic Clinic 64 King St. W. Bolton, Ontario L7E 1C7 hfritz@ccnm.edu

David Miller, BSc, ND 662 Gustavus Street Port Elgin, Ontario N0H 2C0 drdavend@yahoo.ca

Isaac Eliaz, MD, MS, LAc Amitabha Medical Clinic & Healing Center 7064 Corline Ct #A Sebastopol, California 95472-4528 ieliaz@sonic.net

Berchman Wong, ND7 18 - 33 Canniff St Toronto, Ontario M6K 3M5 berchman.nd@gmail.com Betty Rozendaal, BES, MA, ND Thornhill Naturopathic Health Clinic 12A Centre Street Thornhill, Ontario L4J 1E9 info@thornhillnaturopathic.ca

Denisa Maruyama, ND Kona Wellness Center for Integrative Medicine 74-5565 Luhia Street Suite C-2 Kailua-Kona, Hawaii drmayurama@konawellness.com

Brock McGregor, ND McGregor Naturopathic 220 St Clair Street Chatham, Ontario N7L 3J7 drbrock@mcgregornd.com

Elaine Lewis, HBSc, ND Back to Play Chiropractic 592 Rathburn Road West Mississauga, Ontario L5B 3A4 elewis@ccnm.edu

Jiselle Griffith, BSc, ND The Health Hub Integrated Clinic 35 Hayden St, Suite 109 Toronto, Ontario M4Y 3C3 jiselle@healthhubclinic.com

Carol Morley, ND Zawada Health 201 City Centre Drive, Suite 404 Mississauga, Ontario L5B 2G6 info@zawadahealth.com

Elizabeth Cherevaty, BSc, ND Norfolk Chiropractic Wellness Centre 86 Norfolk Street, Suite 101 Guelph, Ontario N1H 4J2 elizabeth.cherevaty@gmail.com

Jordan Robertson, BSc, ND Lakeshore Clinic 2159 Lakeshore Road Burlington, Ontario L7R 1A5 jordanrobertsonnd@gmail.com

Claire Girgis, ND Zawada Health 201 City Centre Drive, Suite 404 Mississauga, Ontario L5B 2G6 claire@zawadahealth.com

Erin Balodis, BSc, MSc, ND Kingswood Chiropractic Health Centre 1210 Hammonds Plains Road Hammonds Plains, Nova Scotia B4B 1B4 erinbalodis@gmail.com

Judah Bunin, BSc, MSc, ND, DrAc

Jacob Scheer, DC, ND, MHSc 2100 Finch Ave. W. #206 North York, Ontario M3N 2Z9 Jacob.Scheer@utoronto.ca

Fredericton Naturopathic Clinic 10-150 Cliffe St, Fredericton, New Brunswick E3A 0A1 frednatclin@yahoo.ca

50 www.ihpmagazine.com l June/July 2013

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

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

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

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

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

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

Kelly Brown, BSc, ND Healthview Therapy Centre 5118 Roblin Blvd Winnepeg, Manitoba R3R 0G9 drkbrownnd@gmail.com

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

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

Leigh Arseneau, ND Centre for Advanced Medicine 670 Taunton Rd East Whitby, Ontario L1R 0K6 info@advancedmedicine.ca

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

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

Lindsay Bast, BSc, ND Greenwood Wellness Clinic PO Box 189 1400 Greenwood Hill Rd. Wellesley, Ontario N0B 2T0 lindsay.bast@greenwoodclinic.ca

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

Louise Wilson, BSc, ND 320 Queen St S, Bolton, Ontario L7E 4Z9 dr.louisewilsonnd@gmail.com

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

Maria Shapoval, ND Canadian College of Naturopathic Medicine 1255 Sheppard Ave East Toronto, Ontario M2K 1E2 mshapoval@ccnm.edu

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

Makoto Trotter, ND Zen-tai Wellness Centre 120 Carlton Street, Suite 302 Toronto, Ontario M5A 4K2 makoto@zen-tai.com

Sarah Vadeboncoeur, ND Ottawa Integrative Health Centre 1129 Carling Ave Ottawa, Ontario K1Y 4G6 sarahmvadeboncoeur@gmail.com

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

Scott Clack, ND Touchstone Naturopathic Centre 950 Southdown Rd, Unit B5 Mississauga, Ontario L5J 2Y4 sclack.nd@touchstonecentre.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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PRODUCT mOnOgRaPh

PRODUCT MONOGRAPH OIL OFPROGRESSIVE OREGANO NUTRITIONAL THERAPIES PHYTOBERRY MULTI + VEGEREENS MULTI

Oil of Oregano is a hydrophobic extract of Origanum vulgare leaf. Major active constituents include the monoterpene critical role that plant foodsand play thymol. in our diet cannot be overstated.

Yet veryare few potent of us consume the recommended of dailybactericidal, phenolicThe compounds carvacrol Carvacrol and thymol antimicrobials withnumber synergistic servings. Thanks to PhytoBerry Multi and VegeGreens Multi, that mission just got a whole lot easier. A single scoop provides the nutritional fungicidal, and antihelminthic activity. density of 6–8 servings of fresh fruit or vegetables, along with over 30 additional vitamins, minerals and support nutrients. the Core Human Study, oxidative and antioxidant status, vegetable and fruit consumption, and carotenoid intake of 68 volunteers was HumanIn studies compared. The results demonstrated that an increased consumption of carotenoid-rich fruits and vegetables increased LDL oxidation

Oil of Mediterranean Oregano antihelminthic given 600 mg with emulsified per day in 14 repair adults who had resistance, and higher plasma had concentration of total andeffects specific when carotenoids wasatassociated lower DNAoil damage and higher activity (Southon (2000)). parasites Blastocystis hominis, Entamoeba hartmanni, and Endolimax nana. After 6 weeks of tested positive for enteric treatment, there was complete resolution parasitic placebo-controlled infection in 8 cases, while hominis decreased in three Nantz et al (2006) conducted a double blind,of randomized, investigation of Blastocystis 59 healthy students (21- 53scores years) consuming a fruitgastrointestinal and vegetable juice symptoms powder concentrate (FVJC)in or 7 placebo for 77 days. was found that FVJC consumption over the 77more cases; improved of thecapsules 11 subjects whoIthad presented with Blastocystis hominis day period resulted in increased nutrients and antioxidant capacity, reduction in DNA strand breaks, and an increase in circulating γδ-T infection.

(Force 2000) cells.

An elevated level of total plasma homocysteine (tHcy) is considered to be a predictor of the mortality risk for all diseases. Panunzio et al

Animal(2003) andinvestigated In vitrowhether studies supplementation of concentrated fruit and vegetables is able to decrease tHcy levels. Twenty-six subjects

participated a cross-over design intervention trial, receiving 2rats capsules fruits and 2 capsules of vegetables a day for 4with weeks, then Carvacrol for oralincandidiasis in immunocompromised was of found to be as effective as treatment Nystatin, reducing acting as his/her own control for another 4 weeks. It was revealed that plasma tHcy concentration was decreased as a result of taking a the number of colony forming units (CFU’s) and completely clearing hyphae from oral surfaces when given for 8 days powdered fruit and vegetable extract on a daily basis, reducing a risk factor causally linked to chronic disease.

(Chami 2004). In vitro, carvacrol was determined to exert an inhibitory effect against 6 different strains of Candida species Cao et alto (1998) examined whether dietplasma rich in fruit and vegetables would affect the antioxidant capacity of human plasma. Thirty-six primarily due extensive lesion of athe membrane (Salgueiro 2003). healthy nonsmokers consumed 2 sets of control diets providing 10 servings of fruits and vegetables each day (for 15 days) with or without Carvacrol has potent antimicrobial activity against several aureus, an additional 2 servings of broccoli each day on days 6-10.

It was microbial observed thatspecies, increasedincluding consumptionStaphylococcus of fruit and vegetables could Bacillus the plasma capacity in humans. subtilis,increase Escherichia coli,antioxidant Psuedomonas aeruginosa, Candida albicans, and Aspergillus niger; out of these, Candida albicans has beenVazir, found (Santoyo 2006). Carvacrol thymol are inthought to exert anyears). additive effectblind, by disrupting et almost (2006)susceptible evaluated the effect of a micronutrient supplementand on mental function children (aged 6 – 15 This double matched-pair, cluster,2001). randomized trial assessed a cohort of 608 to children for intelligence, attention and concentration, bacterialplacebo-controlled, membrane integrity (Lambert Oregano has been shown inhibit Methicillin resistant strains of Staph. memory, and school achievement, before and after 14 months of micronutrient supplementation. Results indicated that supplementation with a range of micronutrients significantly improved attention-concentration over the period of 14 months in children aged 6 – 15 years.

The SHEEP study examined the association between the use a multivitamin supplements and the risk of myocardial infarction (MI). Results were based on data from a large population-based, case-control study of subjects aged 45 – 70 years. The study included 1296 cases (910 men, 386 women) with a first nonfatal MI and 1685 controls (1143 men, 542 women) frequency-matched to the cases by sex, age and hospital catchments area (Holmquist, et al 2003). The results from this study indicate that use of a multivitamin supplements may aid in the primary prevention of MI. Dosage Indication: For the maintenance of good health.

Adults (≥ 18 years)

PhytoBerry Multi Dosage: Mix 1 scoop (17 g) into 250ml of water.

VegeGreens Multi Dosage: Mix 1 scoop (10 g) into 250ml of water or your favourite juice.

Figure 1:Interactions Structure of Carvacrol (left) and Thymol (right) There is insufficient research available regarding the safety of several of the herbal components in children, as a result the use of aureus and epidermis, and attenuates biofilm formation in vitro (Nostra 2004; 2007).

PhytoBerry Multi and VegeGreens Multi is not recommended in children under 18 years of age (Jellin et al (2006)).

Toxicology Due to the potential of toxicity and adverse effects of some of the constituents, PhytoBerry Multi and VegeGreens Multi is not

usecategorically in pregnant or breastfeeding (Jellin al (2006)).

Essentialrecommended oil extractsforare known to women be toxic in ethigh doses, and are therefore typically given in drop doses; components Multi andby VegeGreens may interact with women. medication, Animal diseases and conditions, and/or lab test indicate essentialSome oils the should not bein PhytoBerry used internally pregnantMulti or breastfeeding studies to date, however, results. It is recommended that all ingredients be reviewed before use in an individual under medical supervision, taking prescription relative medication, safety of Oregano oil.a serious and/or pre-existing medical condition (Jellin et al (2006)). suffering from Carvacrol was shown to be hepatoprotective against ischemia and reperfusion injury in rats; both carvacrol and silymarin Quality Assurance Holmquist C, et al (2003). Multivitamin Supplements Are had similar beneficial effects on AST and ALT levels (Canbek 2007).

Carvacrol also increased liver regeneration rate in rats Inversely Associated with Risk of Myocardial Infraction in Men Parameter Test 2008).

Specifications after partial hepatectomy (Uyanoglu and Women – Stockholm Heart Epidemiology Program Microbial (SHEEP).

J Nutr, 133: 2650-2654 Mutagenicity studies of carvacrolUSP show only weak activity; carvacrol is excreted in urine after 24 hours in large quantities, Total Count Less than 5,000 cfu/g JM, et al (2006). Pharmacist’s Letter/Prescriber’s Letter unchanged or &asMold glucoronide andUSP sulphateLess conjugates (De VincenziJellin 2004).

Yeast than 100 cfu/g th

Natural Medicines Comprehensive Database.8 ed. Stockton, Escherichia coli USP Negative CA: Therapeutic Research Faculty.

Salmonella sp USP Negative References Nantz MP, et al (2006). Immunity and Antioxidant Capacity in Staphylococcus aureus USP Negative Humans Enhanced

by Consumption of a Dried, Canbek M, Uyanoglu M, Bayramoglu G, Senturk H, Erkasap N, Koken T,IsUslu S, Demirustu C, Aral E, Husnu Can Baser K. Heavy Metal Encapsulated Fruit and Vegetable Juice Concentrate. J Nutr, Arsenic USEPA < 1.0 ppm Effects of carvacrol on defects of ischemia-reperfusion in the rat liver.

Phytomedicine. 2008 Jan. 136: 2606-2610.

Cadmium USEPA < 0.5 ppm De Vincenzia M et al. Constituents of aromatic plants: carvacrol. Fitoterapia 75(7-8): 801-804. with fruit and Panunzio MF,2004; et al (2003).

Supplementation Lead USEPA < 1.0 ppm Force M et al.

Inhibition of enteric parasites by emulsified oil of oregano in vivo.

Phytother Res. 2000 May;14(3):213-4. vegetable concentrate decreases plasma homocysteine levels Total Mercury USEPA < 1.0 ppm in a dietary controlled trial.concentration Nutrition Research, 23: mode 1221-1228.

Lambert Chemical RJ, Skandamis PN, Coote PJ, Nychas GJ. A study of the minimum inhibitory and of action of Pesticides USP Absent Southon S (2000). Increased fruit and vegetable consumption oregano essential oil, thymol and carvacrol.

J Appl Microbiol.

2001 Sep;91(3):453-62.

Solvents USP Conforms to limits within the EU: potential health benefits. Food Research Nostro A, Roccaro AS, Bisignano G, Marino A, Cannatelli MA, Pizzimenti FC, PL, Procopio F, Blanco AR. Effects of International, 33: Cioni 211-217.

oregano,References carvacrol and thymol on Staphylococcus aureus and Staphylococcus epidermidis biofilms. Jsupplement Med Microbiol.

Vazir S, et al (2006).

Effect of micronutrient on health and nutritional status of schoolchildren: mental function.

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

Cao G, et al (1998). Increases in human plasma antioxidant Nutrition, 22: S26-S32. capacity consumption ofof controlled diets high in fruit and Nostro A et al.after Susceptibility methicillin-resistant staphylococci to oregano essential oil, carvacrol and thymol. FEMS vegetables. Am J Clin Nutr, 68: 1081-1087.

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.

IHP Body Plus.indd 2

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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

IN MEMORIAM

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.

Roger A. Brumback, MD

Dr Brumback completed his residency in paediatrics at John Hopkins Hospital as well as in child neurology at Washington University, St Louis Children’s Hospital. He also completed a fellowship in neurology and neuropathology at the National Institutes of Health. This was preceded by undergraduate and medical training at Pennsylvania State University. Roger has been a Professor of Pathology at the Creighton University School of Medicine in Omaha, Nebraska since 2001. In 1986 he founded the Journal of Child Neurology and has maintained his position as Editor-in-Chief to this day. He likewise accepted the appointment as Editorin-Chief of the Journal of Evidence- Based Complimentary and Alternative Medicine in 2011.

Jason Boxtart, ND

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

Ben Boucher, MD

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

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editorial board

Pardeep Nijhawan, MD, FRCP(C), FACG

Dr. Nijhawan completed his medical school training at the University of Ottawa and proceeded to complete an internal medicine internship at Yale-Norwalk, CT. He completed his internal medicine residency and Gastroenterology and Hepatology fellowship at the Mayo Clinic in Rochester, MN. There he was awarded the Calgary fellowship for outstanding achievements.

He is a member of the Royal College of Physicians and Surgeons of Canada, American Board of Gastroenterology, and American Board of Internal Medicine. In 2003, Dr. Nijhawan established the Digestive Health Clinic to help bring leading edge technology to Canada. He specializes in therapeutic endoscopy, irritable bowel and celiac disease.

Gurdev Parmar, ND, FABNO

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

Kristy Prouse, MD, FRCSC

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

Dugald Seely, ND, MSc

Dr Seely is a naturopathic doctor and director of research at the Canadian College of Naturopathic Medicine (CCNM). Dugald completed his masters of science in cancer research from the University of Toronto with a focus on interactions between chemotherapy and natural health products. In his current role as director of research, Dugald is the principal investigator for a number of clinical trials, and is actively pursuing relevant synthesis research in the production of systematic reviews and meta-analyses. Ongoing projects include three multicentred 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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DHEA Part II Autoimmunity and Bone Health Heidi Fritz, MA, ND Research Fellow, Canadian College of Naturopathic Medicine hfritz@ccnm.edu Bolton Naturopathic Clinic 64 King St W, Bolton, Ontario, L7E1C7

Dehydroepiandrosterone (DHEA) is a weak androgen secreted from the adrenal cortex, and an immunologically active hormone. DHEA supplementation has been shown to improve bone density and metabolism in several patient populations, including the elderly, as well as patients with lupus or anorexia.

DHEA has also been shown to improve measures of disease activity in patients with lupus and inflammatory bowel disease, and may have the ability to reduce steroid medication requirements. In the contexts of bone health and autoimmunity, dosing of DHEA ranges from 50-200mg daily. Adverse effects appear to be limited to acne and hirsutism in women. This paper reviews findings from nine human trials of DHEA for bone health and nine human trials of DHEA in patients with autoimmune disease.

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The Journal of IHP

Introduction

Dehydroepiandrosterone (DHEA), and its sulphated precursor DHEA-S, is a weak adrenal androgen and the most abundant steroid hormone in the body (Andus 2003).

Circulating levels peak during the third decade of life (DHEAS 10ÂľM and DHEA 10nM, slightly lower in women) and decline to approximately 20-30% those levels by the seventh decade of life (Hazeldine 2010). DHEA acts as a precursor for other steroid hormones in the body, including androstenedione, estradiol, and testosterone (Papierska 2012, Weiss 2009), and has been shown to possess immune regulatory

Unfortunately, DHEA is currently banned in Canada due to historical abuse by professional athletes. Nonetheless, as this remains a promising therapy for applications in female fertility (reviewed in Part I) as well as bone health and autoimmune disease, we hope that the status of DHEA may be revisited by Health Canada in the future. and anti-inflammatory effects through various pathways, including inhibition of NF-kappaB activation and inhibition of IL-6 and IL-12 secretion via PPAR-alpha (Andus 2003). DHEA has been shown to inhibit Th2 cytokine secretion associated with asthma in vitro and inhibit bronchial hyperreactivity in vivo (Liou 2011). In older human subjects aged 65-75 years with impaired glucose tolerance, DHEA supplementation (50mg/d) for two years not only improved glucose tolerance but also reduced circulating levels of IL-6 and TNFalpha (Weiss 2011). DHEA has also been

shown to offset the thymic involution that occurs with glucocorticoid administration in animals (Hazeldine 2010, May 1990).

Unfortunately, DHEA is currently banned in Canada due to historical abuse by professional athletes. Nonetheless, as this remains a promising therapy for applications in female fertility (reviewed in Part I) as well as bone health and autoimmune disease, we hope that the status of DHEA may be revisited by Health Canada in the future.

Prasterone is a proprietary, synthetic form of DHEA that is sold as a prescription drug.

1

Bone Health

DHEA supplementation has been shown to increase bone mineral density (BMD) among older adults, patients with anorexia, as well as SLE patients on prednisone therapy (Table 1). As might be expected, this effect seems to be most marked among those with pre-existing bone loss as opposed to those with normal BMD at baseline, as well as among women compared to men (Papierska 2012, Von Muhlen 2008, Weiss 2009). In a study of older men and women on prednisone and with osteopenia, supplementation with DHEA resulted in increased serum IGF-1 and osteocalcin alongside increased lumbar and femoral BMD (Papierska 2012).

Among elderly patients with normal bone density, however, further benefit on BMD from DHEA supplementation appears to be restricted to women, with no significant BMD increase demonstrated among elderly men with normal BMD (Kahn 2002, Von Muhlen 2008, Weiss 2009). The reason for this gender difference is unclear, but may be related to differential hormone metabolism.

Indeed, DHEA supplementation among older adults (25-50mg/d) has been shown to increase serum levels of androstenedione, testosterone, and estradiol particularly in women (Papierska 2012, Von Muhlen 2008, Weiss 2009).

Among patients with SLE, DHEA supplementation has also been shown to significantly improve BMD when compared to placebo (Hartkamp 2004, Mease 2005, Sanchez-Guerrero 2008). A randomized June/July 2013 l www.ihpmagazine.com 57

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The Journal of IHP Table 1. Human Trials of DHEA for Bone Health Design

Intervention

Outcomes

Reference

Older adults, treatment of decreased BMD (T score < -1.5) Prospective trial 19 women, 50-78 years, on prednisone for ≥3y, and bisphosphonate intolerance

Year 1: calcium, vitamin D3 and thiazide diuretics Year 2: micronized DHEA 25-50 mg daily orally

Study included women only: A significant elevation of serum IGF-1 and osteocalcin concentrations was found as early as after 6 weeks of DHEA. • A significant increase of bone mineral density in the lumbar spine and femoral neck was found after 6 and 12 months of DHEA.

•

Papierska 2012

Older adults, prevention of bone loss (T score > -1.5, normal) RCT + open label phase N= 55 men and 58 women aged 65-75 y.

Year 1: RCT of 50 mg/d oral DHEA or placebo Year 2: open-label DHEA phase

•

RDBPCT; N= 225 older adults aged 55 to 85y

50mg DHEA or placebo daily x 1 year

RDBPCT; N= 43 older men, 56-80 years of age.

90 mg/d oral DHEA x 6mo

•

In men, no difference in any BMD or in bone turnover markers during years 1 or year 2.

In women, spine BMD increased by 1.7% (P = 0.0003) during year 1 and by 3.6% after 2y of DHEA supplementation in the DHEA group; in the placebo group, spine BMD was unchanged during year 1 (placebo) but increased to 2.6% c/t baseline in year 2 (DHEA).

Weiss 2009

•

In women, significant increase in lumbar BMD with DHEA (p = 0.03), but no effect was observed for hip, femoral neck or total body BMD. • In men, no change in BMD in men.

• Serum C-terminal telopeptide levels decreased in women (p = 0.03), but not men.

Von Muhlen 2008

•

Study included men only: Mean serum DHEA and DHEA-S in treated men were increased 3-fold after 6 months.

• No significant effect on: procollagen peptide; bone-specific alkaline phosphatase; deoxypyridinoline, or osteocalcin.

Kahn 2002

Systemic lupus erythamatosus, SLE RDBPC cross-over trial N= 13 women w mildmod.SLE (10 on GC)

200mg/d prasterone or placebo x 8wk, with 6wk washout period

• Non-significant trend toward higher RANKL (p=0.097), a marker of higher bone turnover, in prasterone group compared to placebo.

• No effect on disease activity.

Marder 2010

RDBPCT N= 155 women w SLEon chronic GC therapy Open label study, N=144

200mg/d prasterone or placebo x 6mo; followed by open label study of 100 or 200mg/d x 12mo

• Trend for an increase in lumbar BMD with 200 mg/day prasterone x 6mo compared to a decrease in the placebo group (mean 0.003 vs -0.005 g/cm2; p = 0.293).

• Open-label phase: increased lumbar BMD in patients on 200 vs 100 mg/ day (p = 0.021).

• No overall change in hip BMD over 18mo.

SanchezGuerrero 2008

RDBPCT N= 55 women w mildmoderate SLE on GC ≥10mg/d

200mg/d prasterone or placebo x 1y, in addition to regular SLE meds

• In the lumbar spine, there was a mean increase in BMD of 1.7% in the prasterone group compared to a loss of -1.1% with placebo (p = 0.003).

• For the total hip, mean gain was 2.0% in the prasterone group vs a mean loss of -0.3% in the placebo group (p = 0.013).

Mease 2005

RBDPCT N= 60 women w SLEon chronic GC therapy

200mg/d DHEA or placebo x 12 mo

• No difference in BMD in premenopausal women.

• Significant increase in BMD at 12mo with use of DHEA but not placebo among postmenopausal women who were not receiving bisphosphonates or estrogen.

Hartkamp 2004

50, 100, or 200 mg micronized DHEA daily x 3mo

• Urinary N-telopeptides decreased significantly in both the 50mg (p = 0.018) and the 200mg (p = 0.016) groups at 3 months.

• Osteocalcin levels increased in the treatment groups over time (p = 0.002).

Gordon 1999

Anorexia RDBPCT; N= 15 young women with anorexia

Key: BMD bone mineral density; GC glucocorticoid therapy; RDBPCT randomized double blind placebo controlled trial.

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The Journal of IHP Table 2. Human Trials of DHEA for Autoimmune Disease: Impact on Disease Activity Design

Intervention

Outcomes

Reference

Randomized controlled trials, RCTs RDBPCT multicenter N= 381 women w active SLE on standard meds

200mg/d prasterone or placebo x 12 mo

• Among patients with active disease at baseline (SLEDAI), 86 of 147 in the prasterone group (58.5%) had improvement or stabilization, compared to 65 of 146 in the placebo group (44.5%) (p = 0.017).

• Myalgias and oral stomatitis were less frequent in the prasterone group (22% and 15%, respectively) versus placebo (36% and 23%) (P < 0.05 for both).

• C3 complement significantly decreased.

Petri 2004

RDBPCT N= 120 women w active SLE on standard meds

200mg/d prasterone or placebo x 24wk

• Mean reductions in SLAM scores were not significantly different between groups.

• The number of patients with flares was decreased by 16% in the DHEA group (18.3% of DHEA-treated patients versus 33.9% of placebo-treated patients; P = 0.044).

• The mean change in the patients’ global assessment scores was statistically significant between the two groups (DHEA -5.5 vs placebo 5.4; P = 0.005).

Chang 2002

RDBPCT N= 191 women w steroid dependent SLE

100 or 200mg/ dprasterone or placebo x 7-9 mo

• Patients for whom a sustained reduction in the dose of prednisone (≥7.5 mg/day) was achieved for at least the last 2 months of the 7-9-month study period were classified as responders.

• Response rates were 41% in the placebo group, 44% in the 100-mg prasterone group, and 55% in the 200-mg group (P = 0.110, 200 mg versus placebo).

• Among 137 subjects with active disease, 29%, 38%, and 51% were responders (P=0.031).

Petri 2002

RDBPCT N= 21 women with severe active SLE on GC therapy

200mg/d prasterone or placebo x6mo, then 6mo open label

• 11 patients were responders: 7/9 patients on DHEA vs. 4/10 patients on placebo (P<0.10).

• SLEDAI: mean improvement was non-significantly greater with DHEA (P<0.07).

• BMD was significantly reduced in the placebo group, but was maintained in the DHEA group.

van Vollenhoven 1999 [Abstr]

RDBPCT N= 28 women w mild-moderate SLE on GC therapy

200mg/d DHEA or placebo x 3mo

• In the DHEA group the following measures of disease activity improved (decreased): SLEDAI score, patients’ and physician’s overall assessment of disease activity, and concurrent prednisone dosage decreased, while in the patients taking placebo, small increases were seen.

• Lupus flares occurred more frequently in the placebo group (P = 0.053).

vanVollenhoven 1995 [Abstr]

Prospective trial N= 23 women w mild-moderate SLE

50mg/d DHEA starting dose x 6mo

• Significant improvements were found in all lupus outcomes: SLEDAI, SLAM, and others.

Barry 1998 [Abstr]

Prospective trial N= 50 women w mild-moderate SLE

50-200 mg/d DHEA x 12 mo

• DHEA was associated with significant improvements in disease activity: SLEDAI (p < 0.01), patient global assessment (p < 0.01), and physician global assessment (p < 0.05).

• Prednisone doses were significantly reduced (p < 0.05).

vanVollenhoven 1998 [Abstr]

Prospective trial N= 10 women w mild-moderate SLE

200mg/d DHEA or placebo x 3-6 mo

• SLEDAI score and physician’s overall assessment were improved; corticosteroid requirements were decreased.

• Of 3 patients with significant proteinuria, 2 showed marked and 1 showed modest reductions in protein excretion.

vanVollenhoven 1994 [Abstr]

1

Uncontrolled trials

Key: GC glucocorticoid; HSCL-56 56 item Hopkins Symptom Checklist;IGF-1 insulin-like growth factor 1; QOL quality of life; SF-36 standard form 36, a quality of life measure; SLAM Systemic Lupus Activity Measure; SLEDAI SLE Disease Activity Index score.

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placebo controlled double blind study found that DHEA supplementation was also of benefit among young women with anorexia. A dose of 50mg/d was able to restore physiologic DHEA levels within three months, and dosages between 50-300mg were able to improve markers of bone metabolism including osteocalcin and urinary N-telopeptides (Gordon 1999).

Autoimmune Disease Systemic Lupus Erythematosus

A total of eight human trials, five RCTs and three prospective trials, conducted in patients with SLE report significant improvements in disease activity and/ or corticosteroid requirements associated with supplementation of DHEA at a dosage of 50-200mg daily (See Table 2). The Systemic Lupus Activity Measure (SLAM) and SLE Disease Activity Index (SLEDAI) scoring systems were used to assess impact on disease activity.

Four of five RCTs found significant improvements in measures of disease activity, decreased number of disease flares, or reduced prednisone requirements (Chang 2002, Petri 2004, Petri 2002, van Vollenhoven 1995).

Two RCTs demonstrated significant improvements in SLEDAI score with DHEA compared to placebo (Petri 2004, van Vollenhoven 1995). An earlier study by Petri et al found that among patients with active, steroiddependent disease, a significantly greater number of DHEA-treated patients were able to sustain a reduction in steroid dose equal to or greater than 7.5mg/d, defined as responders, compared to placebo (P=0.031). Chang et al found that although there was no significant difference in the SLAM score reductions of patients treated with DHEA or placebo, the number of patients with disease flares was significantly lower in the DHEA group (2002).

DHEA-treated patients also had significantly better global assessment scores (p= 0.005) and fewer serious adverse events, most of which were related to SLE disease flares (p= 0.010) (Chang 2002).

The only adverse events reported with DHEA dosages between 50-200mg/d were acne and hirsutism (Barry 1998, Petri 2004, 2002, van Vollenhoven 1998, 1995, 1994).

Inflammatory Bowel Disease

Abnormally lower DHEA/ DHEA-S levels have been described in patients with inflammatory bowel disease, compared to healthy controls (de la Torre 1998, Straub 1998). One study found that among patients

with ulcerative colitis, DHEA-S was 1350 nmol/L, and in patients with Crohn’s disease DHEA-S was 1850 nmol/L, while healthy controls had a level almost two-fold higher, 3300 nmol/L (p<0.001 and p<0.01 respectively) (de la Torre 1998).

One prospective trial in patients with chronic, active, refractory IBD found that treatment with 200mg DHEA once daily for approximately two months induced remission in 60% of patients (12 of 20 patients in total; six Crohn’s and six ulcerative colitis) (Andus 2003).

Remission was defined as Crohn’s disease activity index <150 or clinical activity index ≤4, which scores eight sign and symptoms of ulcerative colitis, including the number of soft stools; blood in the stools; general wellbeing; abdominal cramps or pain; fever; extraintestinal manifestations; erythrocyte sedimentation rate; and hemoglobin level (Andus 2003).

Subsequent to the publication of this study, the same group of authors published a case report relating the use of DHEA to treat pouchitis (Klebl 2003). A 35-year old women with chronic active pouchitis was treated with 200mg DHEA per day for eight weeks. Her stool frequency dropped from 15-18 per day to eight per day.

Eight weeks after her DHEA treatment was discontinued, the numbers of stools increased again to 12-18 per day and her pain returned, indicating that DHEA was likely responsible for her initial improvement, and that ongoing treatment may be required.

Currently, the small number of studies that have examined DHEA supplementation in patients with Sjogren’s syndrome and rheumatoid arthritis have failed to show benefit (Giltay 1998, Hartkamp 2008, Pillemer 2004, Virkki 2010), however this area deserves further study.

Conclusion

DHEA therapy in the treatment of osteopenia and osteoporosis as well as SLE and IBD is supported by human clinical research. Evidence demonstrates that DHEA can increase BMD in the elderly as well as in patients with SLE or anorexia. DHEA may be a disease-modifying agent in patients with SLE and IBD, decreasing disease activity and acting as steroid-sparing agent. Adverse events reported with use of DHEA 50-200mg for up to one year appear to be limited to mild acne and hirsutism. In future it is hoped that this promising agent may once again become available for human therapeutic application in Canada. ■

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The Journal of IHP References Andus T, Klebl F, Rogler G, Bregenzer N, Schölmerich J, Straub RH. Patientswith refractory Crohn’s disease or ulcerative colitis respond todehydroepiandrosterone: a pilot study. Aliment PharmacolTher.

2003Feb;17(3):409-14.

Barry NN, McGuire JL, van Vollenhoven RF. Dehydroepiandrosterone in systemic lupus erythematosus: relationship between dosage, serum levels, and clinical response. J Rheumatol. 1998 Dec;25(12):2352-6.

Chang DM, Lan JL, Lin HY, Luo SF. Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebocontrolled trial. Arthritis Rheum. 2002 Nov;46(11):2924-7. de la Torre B, Hedman M, Befrits R. Blood and tissue dehydroepiandrosteronesulphate levels and their relationship to chronic inflammatory bowel disease. ClinExpRheumatol. 1998 SepOct;16(5):579-82.

Giltay EJ, van Schaardenburg D, Gooren LJ, von Blomberg BM, Fonk JC, Touw DJ, Dijkmans BA. Effects of dehydroepiandrosterone administration on disease activity in patients with rheumatoid arthritis.Br J Rheumatol. 1998 Jun;37(6):705-6.

Gordon CM, Grace E, Emans SJ, Goodman E, Crawford MH, Leboff MS. Changes in bone turnover markers and menstrual function after short-term oral DHEA in young women with anorexia nervosa. J Bone Miner Res. 1999 Jan;14(1):136-45.

Hartkamp A, Geenen R, Godaert GL, Bootsma H, Kruize AA, Bijlsma JW, Derksen RH. Effect of dehydroepiandrosterone administration on fatigue, well-being, and functioning in women with primary Sjögren syndrome: a randomised controlled trial. Ann Rheum Dis. 2008 Jan;67(1):91-7.

Hartkamp A, Geenen R, Godaert GL, Bijl M, Bijlsma JW, Derksen RH. The effect of dehydroepiandrosterone on lumbar spine bone mineral density in patients with quiescent systemic lupus erythematosus. Arthritis Rheum. 2004 Nov;50(11):3591-5.

Hazeldine J, Arlt W, Lord JM. Dehydroepiandrosterone as a regulator of immune cell function. J Steroid BiochemMol Biol. 2010 May 31;120(2-3):127-36.

Kahn AJ, Halloran B, Wolkowitz O, Brizendine L. Dehydroepiandrosterone supplementation and bone turnover in middle-aged to elderly men. J ClinEndocrinolMetab. 2002 Apr;87(4):1544-9.

Klebl FH, Bregenzer N, Rogler G, Straub RH, Schölmerich J, Andus T. Treatment of pouchitis with dehydroepiandrosterone (DHEA) - a case report. Z Gastroenterol. 2003 Nov;41(11):1087-90.

Kocis P. Prasterone. Am J Health Syst Pharm. 2006 Nov 15;63(22):2201-10.

Liou CJ, Huang WC. Dehydroepiandrosterone suppresses eosinophil infiltration and airway hyperresponsiveness via modulation of chemokines and Th2 cytokines in ovalbumin-sensitized mice. J ClinImmunol. 2011 Aug;31(4):656-65.

Marder W, Somers EC, Kaplan MJ, Anderson MR, Lewis EE, McCune WJ. Effects of prasterone (dehydroepiandrosterone) on markers of cardiovascular risk and bone turnover in premenopausal women with systemic lupus erythematosus: a pilot study. Lupus. 2010 Sep;19(10):1229-36.

Petri MA, Mease PJ, Merrill JT, Lahita RG, Iannini MJ, Yocum DE, Ginzler EM, Katz RS, Gluck OS, Genovese MC, Van Vollenhoven R, Kalunian KC, Manzi S, Greenwald MW, Buyon JP, Olsen NJ, Schiff MH, Kavanaugh AF, Caldwell JR, RamseyGoldman R, St Clair EW, Goldman AL, Egan RM, Polisson RP, Moder KG, Rothfield NF, Spencer RT, Hobbs K, Fessler BJ, Calabrese LH, Moreland LW, Cohen SB, Quarles BJ, Strand V, Gurwith M, Schwartz KE. Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus. Arthritis Rheum.

2004 Sep;50(9):2858-68.

Petri MA, Lahita RG, Van Vollenhoven RF, Merrill JT, Schiff M, Ginzler EM, Strand V, Kunz A, Gorelick KJ, Schwartz KE; GL601 Study Group. Effects of prasterone on corticosteroid requirements of women with systemic lupus erythematosus: a doubleblind, randomized, placebo-controlled trial. Arthritis Rheum. 2002 Jul;46(7):1820-9.

Pillemer SR, Brennan MT, Sankar V, Leakan RA, Smith JA, Grisius M, Ligier S, Radfar L, Kok MR, Kingman A, Fox PC. Pilot clinical trial of dehydroepiandrosterone (DHEA) versus placebo for Sjögren’s syndrome. Arthritis Rheum. 2004 Aug 15;51(4):601-4.

Sánchez-Guerrero J, Fragoso-Loyo HE, Neuwelt CM, Wallace DJ, Ginzler EM, Sherrer YR, McIlwain HH, Freeman PG, Aranow C, Petri MA, Deodhar AA, Blanton E, Manzi S, Kavanaugh A, Lisse JR, Ramsey-Goldman R, McKay JD, Kivitz AJ, Mease PJ, Winkler AE, Kahl LE, Lee AH, Furie RA, Strand CV, Lou L, Ahmed M, Quarles B, Schwartz KE. Effects of prasterone on bone mineral density in women with active systemic lupus erythematosus receiving chronic glucocorticoid therapy. J Rheumatol. 2008 Aug;35(8):1567-75.

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Straub RH, Vogl D, Gross V, Lang B, Schölmerich J, Andus T. Association of humoral markers of inflammation and dehydroepiandrosterone sulfate or cortisol serum levels in patients with chronic inflammatory bowel disease. Am J Gastroenterol. 1998 Nov;93(11):2197-202. vanVollenhoven RF, Park JL, Genovese MC, West JP, McGuire JL. A double-blind, placebo-controlled, clinical trial of dehydroepiandrosterone in severe systemic lupus erythematosus. Lupus.

1999;8(3):181-7.[Abstr] vanVollenhoven RF, Morabito LM, Engleman EG, McGuire JL. Treatment of systemic lupus erythematosus with dehydroepiandrosterone: 50 patients treated up to 12 months. J Rheumatol. 1998 Feb;25(2):285-9.[Abstr] vanVollenhoven RF, Engleman EG, McGuire JL. Dehydroepiandrosterone in systemic lupus erythematosus. Results of a double-blind, placebo-controlled, randomized clinical trial. Arthritis Rheum. 1995 Dec;38(12):1826-31.[Abstr] vanVollenhoven RF, Engleman EG, McGuire JL. An open study of dehydroepiandrosterone in systemic lupus erythematosus. Arthritis Rheum. 1994 Sep;37(9):1305-10.[Abstr] Virkki LM, Porola P, Forsblad-d’Elia H, Valtysdottir S, Solovieva SA, Konttinen YT. Dehydroepiandrosterone (DHEA) substitution treatment for severe fatigue in DHEA-deficient patients with primary Sjögren’s syndrome.Arthritis Care Res (Hoboken). 2010 Jan 15;62(1):118-24. vonMühlen D, Laughlin GA, Kritz-Silverstein D, Bergstrom J, Bettencourt R. Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial. Osteoporos Int. 2008 May;19(5):699-707.

May M, Holmes E, Rogers W, Poth M. Protection from glucocorticoid induced thymic involution by dehydroepiandrosterone. Life Sci. 1990;46(22):1627-31.

Weiss EP, Shah K, Fontana L, Lambert CP, Holloszy JO, Villareal DT.Dehydroepiandrosterone replacement therapy in older adults: 1and 2-y effects on bone. Am J ClinNutr. 2009 May;89(5):1459-67.

Mease PJ, Ginzler EM, Gluck OS, Schiff M, Goldman A, Greenwald M, Cohen S, Egan R, Quarles BJ, Schwartz KE. Effects of prasterone on bone mineral density in women with systemic lupus erythematosus receiving chronic glucocorticoid therapy. J Rheumatol.

2005 Apr;32(4):616-21.

Weiss EP, Villareal DT, Fontana L, Han DH, Holloszy JO.Dehydroepiandrosterone (DHEA) replacement decreases insulin resistance and lowers inflammatory cytokines in aging humans. Aging (Albany NY). 2011 May;3(5):533-42

Papierska L, Rabijewski M, Kasperlik-Załuska A, Zgliczyński W. Effect of DHEA supplementation on serum IGF-1, osteocalcin, and bone mineral density in postmenopausal, glucocorticoid-treated women.

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Sports Nutrition In the context of lifestyle medicine Eva M Selhub, MD 40 Crescent St., Suite 201 Waltham, MA 02453 www.drselhub.com Dreva@theloveresponse.com Alan C Logan, ND Research and Development Consultant, Genuine Health 775 Blithedale Ave, Suite 364 Mill Valley, CA, 94941 aclnd@cfs-fm.org

Introduction

In the course of their practice, integrative healthcare practitioners encounter patients who are on an exercise continuum, a continuum that ranges from sedentary adults with good intentions all the way to elite athletes. The rapid expansion of research under the umbrella term ‘sports nutrition’ is relevant not only to the very small percentage of North Americans who might be considered elite athletes, but may also be of use to more ordinary folks. We argue that central research findings related to nutritional influences on performance can be selectively used as a means to support sedentary adults who may be struggling with initiating and maintaining an exercise program.

Low motivation and high perceived exertion, associated with a lowered mental outlook, are primary obstacles to exercise adherence. We hypothesize that the same nutritional variables that assist in athletic success, including the Mediterranean diet, plant-based antioxidants such as astaxanthin, cherries and beetjuice, fish oil, branched chain amino acids, and creatine, may be factors with much more broad public health implications in terms of being able to support lifestyle change among the ordinary North American population.

There are volumes of international research attesting to the value of regular exercise in the reduction of chronic disease risk, overall mortality, and improvement in mental outlook (Blumenthal 2011). Whereas much has been written concerning the obesity epidemic and the prevalence of sedentary behavior, there are small signs of hope related to participation in moderate intensity physical activity among Canadians. For example, the latest statistics show a 4% increase in the number of physically active Canadians compared to this number in 2003 (Humphreys 2013), and separate data also reflects an increase in time spent in more intense levels of leisure time physical activity (Gilmour 2007). Participation in structured athletics, particularly among females in academic programs, has seen dramatic growth (Shriver 2013). Trends also suggest that North Americans are now more likely to receive physical activity recommendations from healthcare providers - a 40% increase over the last decade (Barnes 2012). Current medical students are more likely to be physically active than the general population, and a high level (69%) of Canadian medical students perceive exercise counseling to be highly relevant to clinical practice (Holtz 2013). Overall,

this signals a beginning of a shift in perception, with both the public and the medical profession recognizing the importance of physical activity, and beginning to implement small lifestyle changes.

None of these encouraging signs, however, should be used to gloss over the staggering realities that despite these changes, only 15% of Canadian adults are meeting current guidelines for physical activity (Colley 2011).

The same research suggesting that soon-to-be physicians believe exercise counseling to be important also shows that 86% of these graduating medical students consider themselves to be ill-prepared for such counseling: 70% reported no training on interacting with patients concerning exercise (Holtz 2013). The more salient point is that integrative healthcare practitioners are increasingly being called upon to provide exercise counseling to patients on a wide spectrum with regard to their comfort and familiarity with physical activity. This spectrum includes Canadians showing the beginnings of interest in the initiating a more active lifestyle for preventive health or for disease management, as well as those who are engaged in elite athletic endeavors. In between these extremes is the so-called “weekend warrior,” engaged in

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irregular patterns of sport participation, and/or those involved in regularly structured athletic programs such are recreational hockey. Part of the valued expertise that integrative healthcare practitioners bring to such encounters with this diverse group of patients is their in-depth knowledge of nutrition as it relates to dietary practices as well as nutritional supplementation.

The Relevance of Nutrition

The lessons learned from recent studies in the realm of nutrition in sports performance may, at first glance, seem to be of little importance, even trivial, when discussing serious and potentially life-threatening conditions, such as depression and obesity. However, investigations aimed at outcomes such as hitting the finish line tape faster, increasing endurance time to fatigue, or pushing just a bit more weight in strength training, ultimately provide nutritional insights with broader potential (Maughan 2011). It is becoming clear that nutrition is a variable relevant to all those who are on the exercise/sport continuum. It has the potential to influence motivation to participate in physical activity; to reduce perception of fatigue, a barrier that often impedes subsequent participation; to influence cognitive readiness for exercise; to enhance the enjoyment of the exercise experience; to enhance recovery for the next bout of physical activity; to minimize the risk of injury; and, genetic endowment and training being equal, to influence performance itself.

Although the term sports nutrition is often associated with having a primary role in support of the muscles (readiness for task, repair, anabolic processes etc.), nutritional influences are also of vital importance for motivation and performance, factors that are centrally regulated through the central nervous system (CNS). In sedentary adults, the motivation to engage in physical activity is low, and the normal post-exercise lift in mood is often not experienced. For example, in those with depression and/or obesity (vs. healthy/normal weight controls), motivation is a primary barrier to physical activity (Searle 2011). Among these patients, despite their awareness of the benefits of exercise, there are lower pleasure ratings reported after exercise, and perceived exertion is much higher while energy levels lower (Ekkekakis 2011), and this in turn impairs intent to participate in future physical activity (Weinstein 2010).

On the other hand, a more positive perception of the experience of exercise encourages future participation (Annesi 2005, Kwan 2010). Integrative healthcare practitioners can take advantage of recent discoveries in nutritional sciences as a means to help break the cycle of negative affect and associated higher levels of perceived exertion, both of which contribute to a generalized exercise intolerance.

The Mediterranean Diet Example

Before discussing more reductionist investigations of single nutrients, e.g. branch chain amino acids, vitamins, minerals etc., it may be worthwhile to examine the influence of the broad aspects of diet as they related to mental outlook and performance. The Mediterranean (Med) diet provides what may be a gold standard for general support of physical and mental performance (Sofi 2010, 2008). The basis of what is now referred to as the contemporary Med diet has been in place for some 10,000 years (Berry 2011), and although details are sparse, there is certainly evidence that various dietary protocols were part of the training schemes of ancient athletes in the region (Grivetti 1997). In the modern context, there are clear characteristics of adherence to a Med diet vs. those consuming standard North American fare (Box 1).

The benefits of high adherence to a Med diet have been well described, ranging from protection against cognitive decline to reduction in the risk of metabolic syndrome (Sofi 2013, 2010, 2008). However, its association with positive mental outlook and resiliency against depressive symptoms bears mention. In a 5-year prospective study, greater adherence to the Med diet was associated with a 25-30% reduction in the risk of depressive symptoms (Sánchez-Villegas 2009).

Moreover, adherence to the Med diet has also been linked to physical performance (Milaneschi 2011). In a recent study, adherence to the Med diet was linked to better objective performance results (measured via selfselected pace and walking speed over a 20m distance) in community-dwelling older adults (Shahar 2012). A recent intervention trial found that a 10-day Med diet significantly increased vigor, alertness and contentment among participants vs. controls (McMillan 2011).

These are precisely the mood changes that would work towards undoing the motivational barriers to exercise.

Among the many mechanisms whereby the Med diet can influence mental outlook, however its ability to reduce inflammatory markers is likely key. Intentional elevation of inflammatory cytokines in healthy adults has been shown to causes low-grade anxiety, depressive

2

• Cereal = 16% more • Vegetables = 38% more • Fruits = 59% more • Fish = 56% more • Meat = 30% less • Fat = more monounsaturated, less saturated • Dairy = 36% less (despite perception, the Meddiet is not high in dairy versus standard diets) Box 1: Patterns of adherence – What constitutes high vs. low Mediterranean Diet adherence? (Adapted from Azzini 2011)

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symptoms and mental fatigue (DellaGioia 2013, Reichenberg 2001), while Med diet interventions are known to reduce systemic markers of inflammation (Richard 2013). The Med diet may in this way psychologically augment the experience of exercise.

Specific Med Diet Elements

Among the specific components of the Med diet, fish intake and carotenoid intake (an accepted marker of fruit and vegetable consumption), have been linked to muscle strength and physical performance (Cesari 2004, Robinson 2008, Semba 2007).

Mechanistically, there is evidence, although not unequivocal, that omega-3 fatty acid-rich fish oil can limit red blood cell deformability, muscle damage and overall inflammation associated with exercise (Mickleborough 2013). Furthermore, omega-3 fatty acids, and eicosapentaenoic acid (EPA) specifically, can potentially influence mental outlook in ways conducive to motivation (Hegarty 2013).

Carotenoids serve as a marker of fruit and vegetable consumption, and their associated array of plant-based antioxidants; there is evidence to suggest that antioxidants may provide benefit in reducing the perception of effort during exercise. For example, compared to controls, heart rate and perceived exertion were reduced, and general fatigue score was decreased, when overweight adults were given 500mg of vitamin C for four weeks (Huck 2013).

Supplementation with the carotenoid astaxanthin for 90 days has been shown to reduce objective markers of muscle cell damage (serum creatine kinase) in elite soccer players (Djordjevic 2012). In another study, 28 days of astaxanthin supplementation (vs. placebo) has been shown to significantly improve cycling performance time among competitive cyclists (Earnest 2011). Other colorful dietary components, cherries for example, have been shown to be helpful in reducing postexercise pain, markers of muscle cell damage and inflammation, as well as a more rapid restoration of muscle strength (Bowtell 2011, Connolly 2006, Howatson 2010).

In addition to omega-3 fatty acids and antioxidants, the Med diet is also very high in dietary nitrate, a compound found in green leafy vegetables and beetroot that can increase blood flow in support of exercise performance. Close to a dozen studies using

beetroot juice, nitrate-depleted beetroot juice and/or supplemental nitrate (Lidder 2013) have shown that dietary nitrate can improve exercise performance by increasing the efficiency of oxygen utilization (O2 cost is reduced) and increasing ATP synthesis.

Among athletes and recreationally fit adults, beetroot significantly increases time to exhaustion (15%), enhances running velocity and reduces perceived exertion over longdistance running, and improves performance in team-sport exercise (Lansley 2011, Murphy 2012, Wylie 2013). One cup of beetjuice contains 5.5 mmol of nitrate, the equivalent of about 350mg; studies have used supplemental dosage forms containing up to 1500mg nitrate in healthy volunteers (Kapil 2010). These findings, showing more efficient metabolic pathways and lowered perceived exertion in particular, clearly suggest potential benefit in those sedentary adults/children who might contemplate initiating an exercise protocol.

Of course, leafy green vegetables also carry significant levels of magnesium (Mg) per serving. Mg plays an important role in enzymatic support of muscular function, and even mild deficiency may compromise muscle performance (Matias 2010). Among athletes, dietary Mg intake is positively associated with various isokinetic strength variables and jumping performance tests, independent of total energy intake (Santos 2011). Mg intake is notoriously low in the general population, and this includes athletes and those with depressive disorders (Santos 2011, Yary 2013). Indeed, low Mg levels have been associated with depressive symptoms, chronic fatigue, and muscular pain. Mg is a versatile nutrient, supporting both muscle and mood; it is one that can help mitigate inflammation and oxidative stress, as well as support normal neurotransmitter functioning (Barbagallo 2009). Again, the relevance of Mg on the continuum, from those struggling to break a sedentary lifestyle to those in which sports performance is part of their identity, seems obvious.

General Considerations â&#x20AC;&#x201C; Protein, Carbohydrate, Hydration

Scientific investigations in the realm of sports nutrition, particularly related to performance outcomes, have made it increasingly clear that a needs-based, individualized approach is most appropriate (Maughan 2011). That

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said, there are general nutritional considerations in supporting the process of exercise adaptation. All forms of exercise increase the rate of protein oxidation relative to the resting state; this translates into an increase in dietary protein demands (Phillips 2012). Of course, increased protein does not imply excess protein – 20 to 25 grams of high-quality mixed protein, or 6g of essential amino acids, consumed before or soon after exercise, is typically more than adequate to support remodeling and adaptive processes in muscle tissue subsequent to exercise (Maughan 2012). Branch chain amino acids (BCAA) have an anabolic effect on human muscle tissue (Borgenvik 2012), and supplemented alone or together with taurine, the BCAAs have been shown to reduce post-exercise muscle soreness (Howatson 2012, Ra 2013). Although not a protein, creatine is a significant nitrogen source, and one that can have value in preventing muscular fatigue (Rawson 2011) and loss of skill under conditions of sleep deprivation at relatively small (2-5g) doses (Cook 2011, Rawson 2011). In keeping with our contention that what is good for the athlete may be good for the sedentary adult seeking motivation, consider that 5g creatine per day has been recently shown to augment the effectiveness of antidepressant medications (Lyoo 2012).

Carbohydrate provides critical fuel for the initiation and maintenance of physical activity, training and/or competition. At lower intensity exercise, the body can take advantage of fat oxidation, however, with increasing intensity (particularly endurance exercise) the demand for carbohydrate utilization grows. Endurance exercise in the fasted state is generally not well tolerated in humans (Maughan 2010), and the increase in perceived effort in those without adequate carbohydrate reserves (glycogen) would certainly not encourage adherence to exercise as medicine (Maughan 2012). For post-exercise recovery efforts, although the science is incomplete, the preponderance of evidence suggests that a 2:1 ratio of carbohydrate to protein supplementation is helpful to restore glycogen reserves (Spaccarotella 2011).

The maintenance of proper hydration is yet another top line consideration in sports nutrition. Progressive loss of water and electrolytes as a result of increasing exercise intensity and duration is itself a cause of fatigue.

The initiation of exercise in a dehydrated state has been shown to compromise performance in endurance (Goulet 2012). Again, the cognitive angle of even the mildest forms of dehydration cannot be overlooked.

Recent studies in schoolchildren and adults have shown diminished cognitive performance in association with mild dehydration, and cognitive restoration produced by correction to a normal hydrated state (Edmonds 2013, Fadda 2012). Perceived exertion is higher among athletes in states of relatively modest hypohydration (Barr 1999), therefore this is likely to be compounded among those who are sedentary. Maintenance of normal hydration

(sodium, potassium, magnesium and calcium) before, during, and after physical activity may go a long way toward encouraging adherence to an exercise program.

Conclusion

Studies derived from the burgeoning area of sports nutrition are not simply of relevance to the very small percentage of North Americans who might be considered elite athletes. IHPs can take advantage of sports nutrition research as a means to support a wide variety of patients/clients, perhaps most importantly those sedentary adults who are struggling with the difficult task of initiating and maintaining an exercise program. Low motivation and high perceived exertion, associated with a lowered mental outlook, are primary obstacles to exercise adherence – the same nutritional variables that might allow an athlete to collect a medal or push an extra rep on a weight bar, are the very factors that might have broad public health implications. ■

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Scand J Med Sci Sports. 2010;20(6):843-52.

Cook CJ, Crewther BT, Kilduff LP, Drawer S, Gaviglio CM. Skill execution and sleep deprivation: effects of acute caffeine or creatine supplementation - a randomized placebo-controlled trial. J Int Soc Sports Nutr 2011;8:2.

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Kapil V, Milsom AB, Okorie M, Maleki-Toyserkani S, Akram F, Rehman F, Arghandawi S, Pearl V, Benjamin N, Loukogeorgakis S, Macallister R, Hobbs AJ, Webb AJ, Ahluwalia A. Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO. Hypertension.

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Insomnia

Role for acupuncture and melatonin Rochelle Fernandes MSc, ND (cand) RD Research Consult 231 Fort York Blvd, Suite 2607 Toronto, ON M5V 1B2 Email: Rd.research.consult@gmail.com

Abstract “Sleep may be the price you pay so your brain can be plastic the next day,” is an intriguing statement by Cirelli and Tononi (Cirelli 2008). The 2002 Canadian Community Health Survey (CCHS) showed that as many as 18% of participants averaged less than five hours of sleep per night (Shields 2005). Sleep is a vital and recurrent function in daily life. It is thought to be an essential component of good health and hypothesized to have the following functions: energy conservation, memory consolidation, regeneration of substrates, and rest. Lack of sleep can have a negative impact on a person’s career, physical activity level, social interaction, mental aptitude and quality of life. There can be a severe economic burden caused by lack of sleep related to motor vehicle accidents, decreased workplace productivity, absenteeism from commitments and health-care costs from co-morbidities. Melatonin and acupuncture are two natural therapies with large bodies of evidence supporting their use in the management of insomnia.

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Features of Sleep and Insomnia

Insomnia is defined as a state of insufficient sleep; it can include difficulties in falling asleep, staying asleep or a combination of both (Balch 2006). Acute insomnia is thought to last less than one to three months on average and consists of difficulty getting to sleep, continuing sleep, and/or sleep is poor quality; resulting in compromised daytime function (AASM 2005). Chronic insomnia can be defined as a failure to get a full night’s sleep on the majority of days in a month. The deleterious impact of insomnia must be considered as an issue on its own and/or as a sign of an underlying major medical diagnoses. There is a plethora of evidence from cognitive, endocrine, neurological, and behavioral disciplines that links insomnia to stress and that attributes insomnia to a state of hyper-arousal and receptor imbalance. Risk factors associated with insomnia include female gender, widowed or single status, low education or income, being unemployed, smoking status, stress, chronic disease, pain, restriction of activity and health dissatisfaction (Sutton 2001).

Sleep is divided into two types: rapid eye movement (REM) and non REM sleep (NREM) with four associated stages, of which the first three are NREM. The four stages of sleep are as follows: Stage one consists of light sleep where one is easily awakened, while stage two consists of theta activity and alpha waves interrupted by k complexes and sleep spindles. Stage three is a deep sleep that consists of slow brain waves, known as delta waves, accompanied by a lack of reaction to environmental stimuli. Stage four consists of the deepest sleep (REM), without major muscle movements (Dement 1975). It is also noted that in this phase, electroencephalogram (EEG) waves are similar to those of an awakened individual.

The Etiology and Physiology of Insomnia

The etiological basis for insomnia includes but is not limited to disturbances in circadian rhythms, stress, genetic conditions, other co-morbid diagnoses, drugs, alcohol, medications and hormonal imbalances. Physiological mechanisms of insomnia include theories that involve the central and autonomic nervous systems (CNS, and ANS respectively). People with insomnia and poor sleep are found to be more alert on daytime alertness tests, such as the multiple sleep latency test (MSLT) (Bonnet 1995, Seidel 1984). They are thought to have altered electroencephalographic (EEG) activity, (beta/gamma) waves at night (Krystal 2002).

Neurological imaging diagnostics such as single photon emission computed tomography (SPECT), positron emission tomography (PET), or proton magnetic resonance spectroscopy (MRS) have shown that insomniacs may have selective hyperactive brain coordinates (Nofzinger 2004, Smith 2002, Winkelman 2008). A highly active ANS that is

found in insomniacs coincides with higher metabolic rates, body temperatures, and heart rates (Freedman 1982). There is a reinforced activation of the hypothalamic-pituitaryadrenal (HPA) axis by corticotrophin-releasing hormone (CRH) (Vgontzas 2001). Additionally, high cortisol levels maintain an increased sympathetic tone. Overall, these explanations suggest that therapeutics designed to restore the balance between the ANS and CNS, by mediating sympathetic and parasympathetic tone, could improve insomnia and optimize sleep quality.

Beyond pharmacotherapy, there are a large number of natural therapeutic options available to patients with insomnia such as melatonin, passionflower, 5-hydroxy tryptophan, L-theanine and acupuncture. It has been suggested that benzodiazepine, melatonin and histamine receptor antagonist activity have all been theoretically linked to insomnia. Supplements should be chosen with the associated mechanisms of action in mind, given the variation in pharmacokinetics. In addition to nutritional applications of treatment, eastern therapeutic strategies such as Traditional Chinese Medicine (TCM) methods have also been efficacious.

Eastern Perspectives in Insomnia

TCM etiologies of insomnia include but are not limited to anger, worry, overwork, excessive sexual activity, irregular diet, and a term known as gall bladder timid and residual heat (Maciocia 2008). It is thought that abnormal yin organs are unable to house essence, thereby causing the person to be restless and awake. The state of the mind and the ethereal soul are crucial to proper sleep. Additionally, internal organ disharmony disrupts essence and essence disrupts the mind; essence and Qi are the roots of the mind and without proper rooting of the mind, insomnia could result (Maciocia 2008). Sleep is contingent on normal functioning of the heart/mind, liver/ethereal soul and the kidneys/will power.

TCM theories are based on organ pair and meridian associated diagnoses resulting from either “full-excess” or “empty-deficiency” conditions. The deficiency or excess conditions are a result of imbalance in the connection between the body and the mind. The full conditions are: liver fire blazing, heart fire blazing, phlegm heat harassing the mind, heart Qi stagnation, heart blood stasis, residual heat in the diaphragm and retention of food (Maciocia 2008). The empty conditions are: heart and spleen blood deficiency, heart yin deficiency, heart and kidneys not harmonized, heart and gall bladder deficiency and liver yin deficiency (Maciocia 2008). The intent is to drain in excess conditions and support/ tonify in deficiency.

TCM strategies of acupuncture and herbal medications are individualized depending on what type of excess or deficient condition the person has. For instance, the

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diagnosis of insomnia as heart fire blazing is treated by needling points such as bladder 15, 44, spleen 6, Ren 15 and Du 19, with a herbal remedy known as XieXin Tang that collectively clears the heart and calms the mind (Maciocia 2008).

Evidence for the Role of Acupuncture in Insomnia

There is a large body of evidence that has shown the efficacy of acupuncture in reducing insomnia by itself or as part of a disease complex.

It is effective as an independent therapy or in conjunction with other treatments. One study utilized the Pittsburgh Sleep Quality Index (PSQI) to compare acupuncture to Zolpidem (10mg) in a psychosomatic clinic of 33 patients with primary insomnia. There were significant improvements in both groups: regression analysis showed the results as a baseline PSQI score of 4.13 (p<0.001), the second score 1.32 (p=0.005), and the third 1.49 (p=0.03), confirming that acupuncture was just as effective as the medication (Tu 2012).

One systematic review examined 33 trials with 2293 patients aged 15 to 98 years of age to assess the safety and efficacy of acupuncture for insomnia alone and with other diagnoses, such as stroke, end-stage renal disease, perimenopause, pregnancy and psychiatric diagnoses. They evaluated needle, electro or magnetic acupuncture and pressure. Compared with no treatment (2 studies, 280 participants) or placebo (2 studies, 112 participants), acupressure resulted in more people with improvement in sleep quality (compared to no treatment: OR 13.08, 95% confidence interval (CI) 1.79 to 95.59; compared to placebo: OR 6.62, 95% CI 1.78 to 24.55) (Cheuk 2012). Compared with other treatment alone, acupuncture combined with other treatment was shown to marginally increase the percentage of people with improved sleep quality (13 studies, 883 participants, OR 3.08, 95% CI 1.93 to 4.90) (Cheuk 2012).

Overall, needle acupuncture showed the highest efficacy out of all the subgroups. Another systematic review demonstrated through the measurement of subjective sleep outcomes that acupuncture reduced sleep latency, increased

sleep and wake ratio (sleep efficiency), resulted in better sleep duration/quality, and minimal insomnia symptoms (Huang 2009).

One interesting, randomized, double blind, placebo controlled trial showed that in postmenopausal women aged 50-67 years old who had insomnia, (as measured by polysomnography exam (PSG) and questionnaires (WHOQOLBREF, Beck Depression Inventory and PSQI)), the acupuncture group had significantly lower scores on the PSQI and improved WHOQOL outcomes after five weeks; confirming that acupuncture improved sleep quality and quality of life in postmenopausal women with insomnia (Hachu 2013). Collectively, the variety of type of studies demonstrate that acupuncture has a measurable improvement on subjective and objective sleep criteria, and that this could potentially be applied to designing individualized treatment strategies for insomnia patients.

Evidence for the Role of Melatonin in Insomnia

Melatonin is a hormone secreted by the pineal gland that regulates circadian rhythm and signals conditions for sleep in the body (Fritz 2009). Administration of exogenous melatonin, typically between 1-5mg under the tongue half an hour before bed, has been shown to decrease sleep latency, increase sleep duration, and increase REM sleep (Brzezinski 2005, Buscemi 2005). Melatonin has also been demonstrated to assist in the discontinuation of benzodiazepine sleeping medications (Garfinkel1999, Kunz 2012). In a randomized controlled trial, 19 of 24 patients who discontinued benzodiazepines using melatonin continued to have good quality sleep six months later (Garkinkel 1999).

Another analysis found that after receiving a prescription for melatonin, one third of patients discontinued use of benzodiazepines (Kunz 2012). Melatonin has been studied in several populations including shift workers, patients on benzodiazepines, patients with idiopathic insomnia, patients with schizophrenia, the elderly including patients with Alzheimerâ&#x20AC;&#x2122;s and Parkinsons, as well as children, including children with neurodevelopmental conditions

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such as Asperger’s, epilepsy, and ADHD (Fritz 2009).

Melatonin has an excellent safety profile, with the exception of concurrent use with calcium channel blockers (CCBs), a blood pressure medication; one study found a small decrease in the effect of CCBs when combined with melatonin (Grossman 2006).

Conclusion

Insomnia by itself or in association with other diagnoses can immensely decrease quality of life, as well as be an increased economic burden on the healthcare system and society. Mechanisms of action thought to be targeted are abnormal melatonin production and receptor function, as well as HPA axis imbalance. Melatonin and acupuncture have shown immense potential in insomnia management and are well supported by a large body of evidence.

Melatonin has been shown in many studies to improve sleep quality and latency, morning alertness and quality of life at a dose range of 2-4 mg for approximately three weeks. Acupuncture has been shown in several studies to improve sleep efficiency, quality and overall quality of life, and even in some studies enabled patients to reduce medication, especially with individualized protocols.

Collectively, these effective natural treatments in addition to targeting the root cause of disease have shown promise in reducing insomnia associated morbidity, and increasing overall wellbeing. ■

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

Effectiveness of Intravenous Vitamin C in Combination with Conventional Chemotherapy in Cancer Treatment: A Review James Bao1, Chloe Haldane1, Yvonne Lee2, Brian Li1, Olesya Petrenko1, Christopher Wang1, Wendy Zhou2, Jordan Robertson ND3 š Bachelor of Health Sciences (Honours), McMaster University ² Bachelor of Health Sciences (Honours) Candidate, McMaster University 3 Bachelor of Health Sciences, McMaster University, Naturopathic Doctor, Canadian College of Naturopathic Medicine

Introduction

Many integrative practitioners are choosing to supplement conventional chemotherapy with intravenous vitamin C (IVC) in cancer patients. Currently, preliminary research has demonstrated the potential benefits of IVC on the length and quality of life in cancer patients. Human- level evidence at this time is limited, yet suggests a role for IV-C as an adjunct treatment for many cancers. There is a strong need for additional research to establish situations the therapy is best suited for, further develop the evidence base of safety in conjunction with conventional therapies, and more clearly delineate the specific outcomes expected from the therapy.

The potential benefits of intravenous vitamin C (IVC) in the treatment of cancer have been debated for several decades. The landmark study conducted by Cameron and Pauling in 1976 was the first to highlight the potential use of vitamin C as a form of medication in the treatment of advanced cancer patients. Since then, clinical studies have reaffirmed that cancer patients exhibit abnormally low plasma ascorbic acid (AA) levels secondary to the disease or treatment, and it is suggested that this contributes to a decrease in survival rate (Shah 2009). Currently, IVC research has been extended to include in vitro, in vivo, and human clinical trials on several cancer types.

Preclinical evidence has provided a number of antitumourigenic mechanisms of high dose vitamin C in cancer (Mikirova 2008, Ohno 2009). Since active transporters tightly regulate intestinal absorption of vitamin C, a desirable concentration of AA can only be achieved via intravenous injection, as opposed to oral administration (Padayatty 2004) (see Figure 1).

Although results from pre-clinical studies in mice have shown a decrease in tumour growth, human clinical trials, thus far, have not found similar results (Chen 2008, Hoffer 2008, Monti 2012). Rather, these studies

show that IVC has limited adverse effects and is a safe and viable treatment to increase quality of life in advanced cancer patients by decreasing the side effects from chemotherapy. Mechanistic studies utilizing cell lines and animal models demonstrate promising results in terms of changing the disease progression itself (Chen 2008). This review hopes to examine any progressions on this theory through evidence provided by recent human clinical trials.

Mechanisms of action based on cell culture studies

Before vitamin C can be investigated as a possible novel cancer treatment, it is essential first to learn whether ascorbate can act as an anticancer agent in cell culture, and if so, by what mechanisms (Chen 2005).

Since the 1980s, the involvement of ascorbic acid has been referenced in a number of studies examining cancer cell proliferation specifically in melanoma cells (Bram 1980), oral squamous cell carcinoma and salivary gland tumour cells (Sakagami 2000). In 2005, Chen and colleagues evaluated the use of AA on human cancer cell lines (lymphoma and three types of breast cancer cell types) and mouse cancer cells (lung, kidney, colon and melanoma) through one-hour incubations at

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pharmacologic concentrations of 0.3-20 mM of vitamin C (Chen 2005). The researchers observed that AA supplementation inhibited growth of breast cancer cells and caused a dose dependent cell death (Chen 2005).

Furthermore, the authors showed that normal tissue cells, such as blood cells, are protected from the toxic effects of AA (Chen 2005).

A number of mechanisms have been proposed to understand how vitamin C functions in decreasing the viability of cancer cells. These include suppression of reactive oxygen species (ROS) on mitochondrial DNA, pro-oxidant function of vitamin C, inhibition of the nitric oxide (NO) pathway, degradation of hypoxia inducible factor-1 alpha (HIF-1 alpha), and maintenance of the extracellular matrix (Cha 2013, Du 2012, KC 2005, Mikirova 2008, Verrax 2008). The majority of in vitro and animal studies have focused on high dosage vitamin C acting as a pro-oxidant via the production of hydrogen peroxide (H2O2) (Chen 2008, Du 2012). By acting as an intermediate and readily donating electrons to redox-active transition metals including copper (Cu2+) or iron (Fe3+), AA reduces the transition metals to cuprous (Cu+) and ferrous (Fe2+) ions, respectively (Frei 2008). The reduced transition metals react with oxygen to produce superoxide radicals, which in turn, dismutate to form H2O2 and O2 (Frei 2008). Normal tissues have adequate blood flow which supplies anti-oxidant enzymes such as catalase and glutathione peroxidase to counter-harmful hydroxyl radicals (Ohno 2009). However, tumour cells have reduced blood flow which leads to an accumulation of H2O2 and subsequent apoptosis of these cells (Ohno 2009) (see Figure 2).

ROS can build up within cells due to intracellular oxidative events and can cause fragmentation of mitochondrial DNA (mtDNA) which is associated with a number of cancer types (Chatterjee 2006, KC 2005). AA has also been shown to protect mtDNA by directly reducing radical species and preventing the formation of reactive species, thereby inhibiting the action of ROS on nuclear DNA repair proteins (Padayatty 2003).

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that upregulates several tumour-growing mRNA transcripts (Verrax 2008). AA is a cofactor of proline hydroxylation and subsequently, the 26S proteasome degradation pathway of HIF-1, which consequently depletes necessary factors for tumour growth, resulting in growth suppression (Knowles 2003, Verrax 2008).

Another way that AA affects tumour cells is by inhibiting NO in endothelial cells (Mikirova 2008).

The NO pathway has been known to be an important

part of tumour angiogenesis and a high dose of AA has been observed to inhibit the production of NO, thereby decreasing blood vessel formation (Mikirova 2008) and preventing tumour growth (Folkmen 1971).

The breakdown of the extracellular matrix (ECM) has been implicated in the formation of tumours and metastasis and the aggressiveness of cancer growth (Cha 2013). Collagen makes up approximately one third of the ECM and serves as a physical barrier against invasion of cancerous cells (Du 2012, Egeblad 2010).

AA is a nutrient required for the synthesis and assembly of collagen, protects against collagen degradation, and prevents proliferation of cancer (Cha 2013).

AA is also known to improve the sensitization of cancer cells to chemotherapy treatments (Heaney, 2008). Seven pathways or mechanisms have been identified to elucidate how AA enhances the effects of cancer therapy drugs. Many of these mechanisms involve the enhancement of membrane transport systems or the activation of tumour suppressor genes (Chiang 1994). As a result, AA reverses chemotherapyresistance and increases the delivery of chemotherapy into cancer cells, increases tumour cell membrane permeability to chemotherapy drugs, stabilizes p53 genes, inhibits translocation of NF-kB and AP1, inhibits Nrf2-mediated gene expression, and activates MLH1, c-Ab1 and p72-signalling cascades (Abdel-Latiff 2005, Bharti 2002, Chiang 1994, Dong 1993, Heaney, 2008, Tarumoto 2004).

In 2001, Reddy and colleagues showed that ascorbic acid stabilizes p53 genes Bax and Bcl2, involved in cancer progression. It has been shown that the absence of p53 leads to abolition of G1 arrest or apoptosis in response to ionizing radiation and DNA damaging agents (Reddy 2001). E6 is an oncoprotein that targets p53 and affect its cell-cycle regulation (Reddy 2001, Scheffner 1990). Reddy and colleagues (2001) showed that vitamin C causes a down-regulation of E6 which in turn causes the up-regulation of pro-apoptotic protein p53 and Bax as well as the down-regulation of apoptotic inhibitor Bcl-2. Accumulation of p53 and Bax then sensitizes the cells to cell-cycle arrest, cell death and apoptosis induced by chemotherapy agents such as cisplatin and etoposide (Reddy 2001).

Another proposed mechanism by which AA provides chemo-sensitization is through inhibition of nuclear factor-kB (NF-k B) and AP-1 (Abdel-Latiff 2005).

NF-kB and AP-1 are nuclear transcription factors that have an effect on genes that promote cancer progression (Bharti 2002, Dong 1993). The former suppresses apoptosis and promotes tumourigenesis, while the latter activates genes involved in tumor June/July 2013 l www.ihpmagazine.com 73

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promotion and progression (Bharti 2002, Dong 1993). Both transcription factors are activated in the presence of chemotherapy agents, thereby causing chemotherapy drug resistance (Abdel-Latiff 2005). Cell cultures studies have shown that AA helps to down-regulate the activity of NF-kB and AP-1, leading to reduced tumour cell proliferation and an improvement in the efficacy of chemotherapy drugs, though the exact mechanism of action of AA on these two factors has yet to be explored (Abdel-Latiff 2005).

Inhibit Nrf2-mediated gene expression

Ascorbic acid also inhibits Nrf2mediated gene expression which results in greater sensitivity of cancerous cell to chemotherapeutic drugs. Nrf2 is a member of the family of basic regionleucine zipper transcription factors that migrates into the nucleus under conditions of oxidative stress (Tarumoto 2004). In the nucleus, Nrf2 regulates gene expression of a number of detoxifying enzymes such as -glutamylcysteine synthetase ( -GCS), the rate-limiting enzyme in glutathione (GSH) synthesis via the antioxidant response element (ARE)- mediated gene expression (Tarumoto 2004). GSH is involved in resistance to some anti-cancer drugs, including cisplatin and doxorubicin (Iida 1999). Ascorbic acid works to suppress the migration of Nrf2 to the nucleus, thus resulting in inhibition of GSH synthesis and restoration of sensitivity of cancerous cells to chemotherapy (Tarumoto 2004) Lastly, ascorbic acid has been shown to activate MLH1, and p73 cascades. Mut L homologue-1 (MLH1) is a component of the DNA mismatch repair machinery which allows the removal of mismatches that occur during DNA replication, genetic recombination and DNA damage (Catani 2002). Defects in this gene lead to an accumulation of replication errors and can result in colorectal cancer (Peltomaki 2001). The response to DNA damage involves MLH1 which can activate c-Ab1 tyrosine kinase which then initiates the p53 homologue p73 which improves cellular susceptibility to apoptosis (Catani

2002). This susceptibility is crucial because chemotherapy agents work by causing DNA damage and depend on the cellâ&#x20AC;&#x2122;s apoptosis as a method of killing the tumour (Catani 2002).

PRE-CLINICAL STUDIES Mouse Models

The ability of genetically engineered mice to mimic the pathophysiological and molecular features of human malignancies has allowed mouse models to become the most sophisticated animal model for human cancer (Frese 2007). A number of IVC studies have been conducted on mouse models in which decreased tumour growth and tumour volume were observed.

However, since most of these studies did not investigate the effects of AA as a cotreatment to chemotherapy, the beneficial effects of AA may be underestimated.

A 1988 study by Tsao et al. reported that AA inhibited the growth of human mammary tumours in immunocompetent mice that were administered AA in drinking water and given a diet with cupric sulfate. AA as a dietary additive alone was ineffective, which supports the theory that the inhibitory effect of AA is due to H2O2 production as Cu2+ is known to catalyze the production of H2O2 in the presence of AA. Following their in vitro study in 2005, Chen et al. in 2008 applied AA as a treatment option to ovarian, pancreatic and glioblastoma tumour xenografts in mice and found that a high dose of vitamin C (4g/ kg body weight), injected intraperitoneally, decreased tumour growth and weight of all three cancers in the range of 41-53% (Chen 2008). The authors attributed this reduction to H2O2 generation in the extracellular medium of tumour cells by the AA radical (Chen 2008).

Belin et al. (2009) conducted a study in which nude mice were injected with human colon adenocarcinoma cells and the treatment group was treated with high concentrations of AA (1000 mg/kg/day) while the control group received only 15/ mg/kg/day of AA. A decrease in tumour growth was only observed in the treatment group. Furthermore, four out of seven mice

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in the control group died during the course of the experiment. Thus, it was concluded that a high dose of AA given to cancerous mice will prevent invasive carcinogenic processes (Belin 2009).

Another study by Espey et al. (2011) applied IVC therapy in combination with gemcitabine, a chemotherapeutic agent used to treat pancreatic cancer.

After implanting tumour cells into the flanks of mice, the authors divided the mice into four treatment groups: gemcitabine alone, AA alone, combination therapy and saline control (Espey 2011). They found that combination therapy was superior in reducing tumour volume and weight relative to gemcitabine treatment alone (Espey 2011). No adverse effects were recorded except for osmotic stress due to the sodium component of pharmacologic AA administration (Espey 2011).

Recently, Cha et al. (2013) used the collagen pathway to test the efficacy of AA on breast and melanoma cancer cell lines in knockout mice that are unable to synthesize AA. The mice were maintained on or deprived of AA in their diet for four weeks prior to and two weeks after intraperitoneal injections of melanoma and breast cancer cells (Cha 2013). AA supplemented mice showed a 28% tumour weight reduction as compared to the controls (Cha 2013). This provides further evidence that supplemented AA hinders metastasis, tumour growth and encapsulation of tumours (Cha 2013).

HUMAN TRIALS Disease Progression

There is limited evidence exploring the efficacy of chemotherapy plus IVC in humans. Since 2008, three phase I clinical trials have been conducted, which have demonstrated the safety of IVC alongside chemotherapy (Hoffer 2008, Monti 2012, Welsh 2013). A handful of human trials conducted before 2008 are also reviewed and included in Table 1. First, Hoffer et al. (2008) conducted a dose-seeking trial in patients with advanced tumour malignancy. The study results concluded that a safe dose of 1.5 g/kg of vitamin C can be used for future phase II trials and established that there were few adverse effects in both groups - with or without vitamin C administration (Hoffer 2008). The authors postulated that these adverse effects were related to the rapid infusion of a high osmolarity solution and could have been prevented by increased fluid intake (Hoffer 2008). With regards to the treatment, however, they reported no significant difference in life expectancy and no anti-tumour activity (Hoffer 2008).

The second phase I trial, conducted by Monti et al. (2012), aimed to establish safe levels of IVC

administration alongside gemcitabine and erlotinib among patients with stage IV pancreatic cancer. The purpose was to evaluate whether the predicted AA levels could be achieved and to assess any response to the treatment (Monti 2012). The safety data did not reveal any adverse events irregular to the normal progression of pancreatic cancer or use of gemcitabine and erlotinib (Monti 2012).

Most recently, Welsh et al. (2013) aimed to establish the safety and tolerability of pharmacological AA alongside conventional gemcitabine in patients with stage IV pancreatic adenocarcinoma. Using disease burden, weight, performance status, time to progression, hematologic/metabolic tests and overall survival as outcome measures, the data suggested that pharmacologic vitamin C, alongside gemcitabine administration, is well tolerated.

Since these are phase I safety and dose-escalation trials, conclusions relating to the efficacy of vitamin C as a contributor to disease recession cannot be drawn. It should be noted that current phase I studies have only examined pancreatic cancer patients, which may not be representative of all cancer types. It is also important to note the lack of power when considering the conclusions of the aforementioned studies. Currently, the published evidence on the effectiveness of IVC treatment in conjunction with chemotherapy is limited to phase I clinical trials. There are three ongoing clinical trials investigating the safety of IVC therapy (phase I) (clin trials.gov NCT01833351), progressionfree survival (phase II) (clin trials.gov NCT01555489) and toxicity (phase II) (clin trials.gov NCT01754987), to provide better evidence for the role of AA in cancer therapy for the future.

Quality of Life

For patients facing the heavy disease burden of cancer and suffering from the side effects of treatment, improvement in quality of life may be equally as important as finding a cure. Several studies have suggested that IVC therapy may play a role in improving quality of life measures. A prospective study by Yeom et al. (2007) followed 39 terminal cancer patients over a one week period. Patients were asked to stop chemotherapy treatment and were administered 10g of vitamin C intravenously twice over the study period (Yeom 2007). Quality of life was assessed after the study period using a self-administered questionnaire. Patients reported a significant increase in overall quality of life as well as significant improvement in all areas of function (physical, role, emotional, cognitive and social).

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Table 1: Clinical trials.

Reference

Design

Outcome

Phase I trials published after 2008 Welsh 2013

Phase 1 trial involving 9 stage IV pancreatic cancer patients given15-125g IVC, twice a week for 6 months, in combination with gemcitabine.

There was no dose limiting toxicities or adverse effects found when IVC was administered with gemcitabine. Some efficacy suggested but this could be the result of gemcitabine alone.

Monti 2012

Phase 1 trial involving 14 stage IV pancreatic cancer patients given 50-100g IVC, 3 times a week for 8 weeks, in combination with gemcitabine or erlotnib.

There was no increased toxicity with the addition of IVC to conventional pancreatic cancer treatment.

Hoffer 2008

Phase 1 trial involving 24 patients (various types) given 0.4-1.5g/kg IVC in a dose escalated manner, 3 times a week in a 4 week cycle.

Adverse events and toxicity were minimal at all dose levels. Anti-tumour activity was limited. High dose IVC administration was well tolerated.

Other human trials published after 2008 Mikirova 2012

Time series study involving 45 cancer patients (various types) given 7.5g-50g IVC, 3 times a week after patients had received conventional therapy.

IVC was effective in reducing inflammation in cancer patients and no adverse side effects were observed.

Vollbracht 2011

Retrospective cohort study involving 125 breast cancer patients given 7.5g IVC, once a week with standard therapy (n=53) or standard therapy alone (n=72) over 4 weeks.

Complementary treatment of breast cancer patients with IVC is well tolerated and reduced quality of life side-effects.

Chen 2008

Cross sectional study involving 8 cancer patients (Various types) given 15-100g IVC in a dose escalated manner.

Pharmacologic plasma ascorbate concentrations can be attained in humans using IVC therapy. Use of IVC as a single agent was not curative.

Human trials published before 2008 Block 2007

Systematic review of 10 studies examining single or combination antioxidant therapy in combination with chemotherapeutic treatment regimes.

No evidence was found that supported concerns that antioxidant supplementation concurrently with chemotherapy diminished the efficacy of treatment.

Berenson 2007

22 multiple myeloma patients received arsenic trioxide, bortezomib and 1g IVC on days 1, 4, 8 and 11 of a 12 day cycle for a maximum of 8 cycles.

Objective responses were observed in 6 subjects. 12-month progressionfree survival rate was 34%. Overall survival rate was 74%.

Yeom 2007

39 terminal cancer patients received 1g IVC, twice a week for one week, plus 4g oral vitamin C, daily. Patients were asked to discontinue chemotherapy.

Functional scores demonstrated statistically significant improvement in various quality of life measures including fatigue, nausea, pain and appetite loss.

Berenson 2006

65 multiple myeloma patients received melphalan, arsenic trioxide and 1g IVC combination therapy, twice a week for 6 weeks.

Objective response occurred in 48% of patients including 2 complete, 15 partial and 14 minor responses.

Padayatty 2006

3 cases of advanced cancer demonstrating exceptionally long survival following intravenous vitamin C therapy.

Found that only intravenous route produces cytotoxic concentrations of vitamin C. The role of IVC therapy in cancer treatment should be reassessed.

Wu 2006

20 multiple myeloma patients were given arsenic trioxide, dexamethasone and 1g IVC combination therapy, 5 times a week for the first week then twice a week for 3 weeks after.

Clinical response was seen in 40% of patients. Median duration of response was 5 months. Median overall survival was 11 months.

Riordan 2005

24 late stage terminal cancer patients were given 150-710mg/kg/ day IVC for up to 8 weeks.

Most common adverse effects were nausea, edema and dry mouth/skin (all minor). Ascorbate infusions did not adversely affect renal function.

Drisko 2003

2 cases of remission of advanced ovarian cancer given 60g IVC, twice a week in combination to carboplatinum / paclitaxel chemotherapy.

Both patients remained disease free at time of publication. One patient had been followed for 3.5 years, the other patient for 3 years.

Bahlis 2002

6 patients with relapsed/refractory myeloma received 0.25mg/kg/ day arsenic trioxide + 1g/kg/day IVC for 25 days over a 35 day period

Two patients had partial response, four patients achieved stable disease.

Dose-limiting toxicity did ot occur in any patient.

Cameron 1991

1826 cases of “incurable” cancer were followed over 4.5 years with 294 of these patients administered 1000mg vitamin C orally, IV or both.

Mean survival time among vitamin C supplemented patients was 343 days versus 180 days in control patients. A clear linear relationship was observed for maximum plasma ascorbate level and survival time.

Campbell 1991

A case report of terminal reticulum cell sarcoma managed with IVC.

Patient was disease free after 17 years at the time of publication.

Cameron 1976

100 patients with “untreatable” cancers were given 10g IVC per day for 10 days followed by oral dosing of 10g per day thereafter.

The mean survival time for IBC treated subjects was 210 days versus 50 days in disease matched controls.

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Various symptoms were also improved including fatigue, nausea/vomiting, pain, sleep disturbance and appetite loss.

A retrospective cohort study conducted by Vollbracht et al. (2011) examined how IVC affected the quality of life of breast cancer patients. The study gathered 125 patients from different cancer clinics, of which 53 formed the study group and 72 formed the control group (Vollbracht 2011). Patients in the study group received 7.5g of IVC once a week for a minimum of four weeks along with standard antineoplastic interventions (surgical treatment, chemotherapy, radiotherapy or hormone therapy). The control group did not receive adjuvant IVC therapy. The main outcome measures include intensity of complaints due to disease or therapy during treatment and after care. After adjusting for age and baseline scores, the study found statistically significant results supporting the benefits of IVC on ameliorating side effects of treatment such as loss of appetite, fatigue, sleep disorders, and nausea (Vollbracht 2011). This study also reaffirmed the safety of IVC administration in conjunction with conventional cancer treatments.

For patients undergoing chemotherapy or radiation therapy, vitamin C may help to improve quality of life measures by increasing overall anti-oxidative capacity.

Since mucosal and nerve cells are particularly susceptible to oxidative stress, increased vitamin C plasma levels may protect against gastrointestinal symptoms such as diarrhea (Vollbracht 2011). Vitamin C may also protect against the degradation of neurotransmitters commonly associated with oxidative stress, possibly explaining its antidepressant-like effects (Vollbracht 2011).

APPENDIX:

Figure 1: Oral vs. Intravenous Vitamin C Peak plasma vitamin C concentrations after oral administration (1-3 g) is in the range of 0.15-0.2 mM. This level is not sufficient to achieve cytotoxicity in tumour cells, which requires a peak plasma level of 1-10 mM. Comparatively, the peak plasma vitamin C concentration with the administration of intravenous vitamin C (10-100 g) is 5-15 mM, which falls in the cytotoxic range for tumor cells. Moreover, both oral and intravenous vitamin C administration avoid cytoxicity in normal cells, which requires a peak plasma level of greater than 20 mM (Ohno 2009).

CONCLUSION:

Thus far, current data on the use of IVC as an adjunct therapy to conventional cancer treatments shows promise. While preclinical studies demonstrate the potential for AA to have cytotoxic effects on cancer cells via numerous pathways, hydrogen peroxide being the primary one, recent human trials have not yet proven these effects. However, IVC has been shown to improve the quality of life of cancer patients.

Vitamin C’s relatively low-cost, easy accessibility and few treatment side effects further reinforce that its benefits should not be dismissed or overlooked. This review is a call for further research into the efficacy of conventional cancer treatment versus treatment in conjunction with IVC on a larger scale. Such data will help validate IVC as an integral component of standard cancer care and encourage physicians to consider this integrative treatment for their patients.

Figure 2: Pro-oxidant function of Ascorbate Free transition metals, such as copper and iron, are reduced by ascorbate and react with hydrogen peroxide (H2O2). This leads to the formation of highly reactive and damaging hydroxyl radicals. Normal tissue receives adequate blood flow and is rich in antioxidant enzymes (e.g. catalase, glutathione peroxidase) in the blood and thus the H2O2 that is formed can be efficientlyquenched.

Comparatively, tumour tissue often has reduced blood flow and antioxidant enzymes and consequently H2O2 that has formed remains active, leading to cell damage and death (Ohno 2009).

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Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, Wesley R A, Levine M. Vitamin C pharmacokinetics: Implications for oral and intravenous use. Ann Intern Med. 2004 Apr;140(7):533-7.

Tsao SC, Dunham WB, Leung PY. In vivo antienoplastic activity of ascorbic acid for human mammary tumor. In Vivo. 1988 MarApr;2(2):147-50.

Verrax J, Calderon PB. The controversial place of vitamin C in cancer treatment. Biochem Pharmacol. 2008 Dec;76(12):1644-52. doi: 10.1016/j.bcp.2008.09.024 Vollbracht C, Schneider B, Leendert V, Weiss G, Auerbach L, Beuth J. Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany. In Vivo. 2011 Nov-Dec;25(6):983-90.

Welsh JL, Wagner BA, van’t Erve TJ, Zehr PS, Berg DJ, Halfdanarson TR, Yee NS, Bodeker KL, Du J, Roberts LJ 2nd, Drisko J, Levine M, Buettner GR, Cullen JJ. Pharmacological ascorbate with gemcitabine for the control of metastatic and nodepositive pancreatic cancer (PACMAN): results from a phase I clinical trial. Cancer Chemother Pharmacol. 2013 Mar;71(3):76575. doi: 10.1007/s00280-013-2070-8.

Wu KL, Beksac M, van Droogenbroeck J, Amadori S, Zweegman S, Sonneveld P.Phase II multicenter study of arsenic trioxide, ascorbic acid and dexamethasone in patients with relapsed or refractory multiple myeloma. Haematologica. 2006 Dec;91(12):1722-3.

Yeom CH, Jung GC, Song KJ. Changes of terminal cancer patients’ health-related quality of life after high dose vitamin C administration. J Korean Med Sci. 2007 Feb;22(1):7-11.

Peltomaki P. Deficient DNA mismatch repair: a common etiologic factor for colon cancer. Hum Mol Genet. 2001 Apr; 10(7): 735-40 Reddy VG, Khanna N, Singh, N. Vitamin C augments chemotherapeutic response of cervical carcinoma HeLa cells by stabilizing p53. Biochem Biophys Res Commun. 2001 Mar;282(2): 409-15 Riordan HD, Casciari JJ, González MJ, Riordan NH, MirandaMassari JR, Taylor P, Jackson JA.A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. P R Health Sci J. 2005 Dec;24(4):269-76.

Sakagami H, Satoh K, Hakeda Y, Kumegawa M. Apoptosisinducing activity of vitamin C and vitamin K. Cell Mol Biol (Noisy-le-grand). 2000 Feb;46(1):129-43.

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Questions 1. T he first researchers to demonstrate anticancer activity of intravenous vitamin C were a) Watson and Crick b) Leibniz and Newton c) Pauling and Cameron d) Drisko and Riordan

2. Anti-tumor activity of vitamin C is associated with intravenous as opposed to oral administration. The reason for this is a) Activation of immune cells in the lymph nodes and venous system is necessary for vitamin C to have anticancer effects; b) I ntestinal absorption of vitamin C is limited, whereas intravenous administration achieves blood concentrations requires for anticancer activity; c) Patients with advanced cancer are so nutrient deficient that they require high dosages of vitamin C to restore the antioxidant capacity of the body; d) All of the above.

3. Based on in vitro studies, the pro-oxidant effect of vitamin C is considered the most important mechanism of action of IVC. High dose vitamin C acts as a pro-oxidant via the production of hydrogen peroxide (H2O2). Normal cells have adequate catalase to breakdown H2O2, howevertumour cells have reduced ability to breakdown H2O2, which leads to the accumulation of H2O2 and selective apoptosis of these cells. a) True b) False 4. High dose vitamin C may also sensitize cancer cells to the effects of chemotherapy drugs. This is thought to happen by upregulation of p-glycoprotein and inhibition of p53 genes. a) True b) False 5. Two recent Phase I studies indicate the safety of IVC administration in patients with pancreatic cancer receiving therapy which of the following chemotherapy drugs? a) Doxorubicin b) Cisplatin c) Oxaliplatin d) Gemcitibine

6. C urrently, published evidence on the efficacy of IVC in conjunction with chemotherapy is characterized by which of the following? he highest level of evidence showing antitumor effects of IVC a) T is a 2012 meta analysis. b) T he highest level of evidence showing antitumor effects of IVC are 3 RCTs published post-2008. c) The highest level of evidence showing antitumor effects of IVC are Phase I trials. d) None of the above.

7. IVC has been shown to improve the quality of life of cancer patients. Which of the following is true? a) In patients with advanced cancer who stopped chemotherapy, 50g vitamin C twice weekly was shown to improve quality of life and physical function. b) I n patients still receiving standard anticancer therapies, addition of 7.5g vitamin C intravenously was able to improve side effects of chemotherapy. c) In patients with advanced cancer who stopped chemotherapy, 10g vitamin C twice weekly was shown to improve fatigue, nausea/vomiting, pain, sleep disturbance and appetite loss. d) B and C 8. An important systematic review by Keith Block MD in 2007 concluded that there is a lack of evidence for the claim that the administration of antioxidants reduces the efficacy of chemotherapy. a) True b) False 9. In addition to the drug in question five, other chemotherapy drugs that have been investigated alongside IVC include: a) Bortezomib, herceptin, melphalan, carboplatin, paclitaxel b) Bortezomib, erlotinib, melphalan, gemcitibine, paclitaxel c) Bortezomib, erlotinib, melphalan, carboplatin, paclitaxel d) Bortezomib, erlotinib, melphalan, dacarbazine, paclitaxel 10. T here is a need for further research on the efficacy of IVC. Currently, there are three ongoing clinical trials investigating the safety of IVC therapy (phase I), as well as effects on progressionfree survival (phase II) and the toxicity of IVC (phase II). a) True b) False

Fax or email answers to: 416.703.6392 or philip@ihpmagazine.com Name: Address: City: Province: Postal Code: Phone: Email: Fax: Practice Registration #:

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PRODUCT mOnOgRaPh

OIL OF OREGANO

PRODUCT MONOGRAPH activrecover+ and plant-based activrecover+

activrecover+ is a sportsisnutrition supplementextract designedof specifically for postexercise Thisconstituents new formula from genuine health complements activfuel+, Oil of Oregano a hydrophobic Origanum vulgare leaf.consumption.

Major active include the monoterpene its sister formula, which supplies nutrients required before and during exercise to maximize energy production and improve performance. activrecover+ on the other phenolic compounds carvacrol and thymol.

Carvacrol and thymol are potent antimicrobials with synergistic bactericidal, hand provides nutrients to support the third stage of performance – recovery – and assist with repairing and building muscle. The formula activrecover+ is designed fungicidal, and protein antihelminthic to provide high quality and include activity. branched chain amino acids post-workout, help replace glycogen stores, improve recovery time, and support optimal immune function, all with the end result of ultimately elevating performance. activrecover+ is effective in conjunction with exercise of any intensity.

Human studies

Rebuild Oil of Mediterranean Oregano had antihelminthic effects when given at 600 mg emulsified oil per day in 14 adults who had Whey protein isolate is a complete protein source delivering all nine essential amino acids and helps meet the higher protein demands associated with physical parasites Blastocystis Entamoeba and Endolimax 6 weeks tested positive enteric activity (Fulgoni 2008).for Exercise increases protein requirementshominis, 1) up to 25% to maintain hartmanni, existing muscle mass, and 2) up tonana.

50% to After gain muscle massof (Lemon treatment, thereincreases was complete resolution ofregulate parasitic infection in 8 cases, while Blastocystis hominis scores(from decreased inasthree 1997).

Dietary protein thermogenesis and helps blood glucose. According to one study, even a 3% increase in protein 15 to 18% a percent of total calories) was associatedsymptoms with greater fat loss and the to keep it off after who 6 months Joneswith 2008).Blastocystis Plant-based activrecover+ more cases; gastrointestinal improved inability 7 of the 11 subjects had(Paddon presented hominis contains plant- based protein derived from yellow peas and potatoes.

infection. (Force 2000)

Branched chain amino acids (leucine, isoleucine, valine) are anabolic and promote muscle synthesis. In addition, research has shown that BCAAs decrease muscle Animal and In vitroduring studies protein breakdown (catabolism) exercise; improve motivation and performance by decreasing the mental perception of fatigue; improve reaction time during performance; lower the stress hormone cortisol during recovery; reduce the typical onset muscle soreness (DOMS) associated with exercise; reduce Carvacrol forlevels oralofcandidiasis in immunocompromised rats was founddelayed to be as effective as treatment with Nystatin, reducing muscle associated with exercise (Howatson 2012, Shimomura 2010). thefatigue number of colony forming units (CFU’s) and completely clearing hyphae from oral surfaces when given for 8 days

(Chami In its vitro, carvacrol determined exert an inhibitory effect against 6 different strains2012). of Candida species Creatine is well2004). known for ability to increasewas strength and fat freetomass especially in conjunction with resistance training (Cooper Creatine acts as a primarily toregeneration extensive lesion of the plasma (Salgueiro 2003). phosphorus donordue in the of ATP from ADP via themembrane ATP- phosphocreatine energy system, a crucial anaerobic energy source during high intensity activity as well ashas in between of high intensity activity (Cooperseveral 2012). In addition, a species, recent study demonstrated creatine’s abilityaureus, to reduceBacillus markers of muscle Carvacrol potentbouts antimicrobial activity against microbial including Staphylococcus damage (serumEscherichia creatinine kinase, as well as improve joint rangeCandida of motion and muscle and soreness following repeated boutsofofthese, resistance training albicans (Veggi 2013). subtilis, coli,CK), Psuedomonas aeruginosa, albicans, Aspergillus niger; out Candida

has been most susceptible (Santoyo 2006).

Carvacrol thymol thought to exert additive effect by disrupting Glutamine is an found important fuel for immune cells, particularly neutrophils, storedand within skeletalare muscle (Lagranha 2008).an Glutamine helps optimize immune function bacterial membrane (Lambert(Cury-Boaventura 2001). Oregano hasInbeen shown to inhibit Methicillin resistant strains Staph. to prevent overtraining inducedintegrity immune suppression 2012). addition, glutamine may help offset loss of lean muscle mass of during acute illness: during infection, the body mobilizes muscle stores of glutamine in order to feed the immune system, thereby catabolizing muscle mass (Lightfoot 2009).

Administering supplemental glutamine during this time may help offset this effect and maintain lean body mass.

Re-Energize activrecover+ provides approximately 20g carbohydrates from corn, brown rice, and orange. Depletion of glycogen stores is a key factor in determining the amount of time required for exercise recovery, and the post-exercise consumption of carbohydrates is the most important factor in replenishing glycogen (Beelen 2010).

Consumption of protein/ amino acids in addition to carbohydrates post exercise causes insulin release and boosts the glycogen replacement rate (Beelen 2010).

Restore Lemon verbena extract possesses antioxidant effects and has been shown to reduce muscle damage and offset neutrophil damage in athletes in response to chronic running eccentric exercise (Funes 2011). Tart cherry juice has been shown to reduce muscle pain following running exercise (Kuehl 2010) and attenuate the reduction in muscle strength following exercise, with a 22% loss of strength in the placebo group compared to only 4% in the tart cherry juice group (Connolly 2006).

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

aureustoand epidermis, andrestoring attenuates biofilm formation (Nostrain2004; Directions: rebuild muscles while energy, mix one scoop (40g)inofvitro activrecover+ one to 2007). one and a half cups (250-375mL to taste) water. For best results, take 1 serving immediately after exercising. For maximum effectiveness, take 1 additional serving 1-2 hours later based on body weight and exercise Toxicology intensity.

Take separately fromare products containing known caffeine (eg. coffee, cola, for a minimum 4 weeks. Consult a healthcare prior to use if you Essential oil extracts categorically to be toxic in etc). highUse doses, and are of therefore typically given inprovider drop doses; are pregnant or breastfeeding, following a low protein diet, or if you have kidney or liver disease. May result in weight gain. essential oils should not be used internally by pregnant or breastfeeding women. Animal studies to date, however, indicate relative safety of Oregano oil.

Table 1. activrecover+ and plant-based activrecover+ formula, per 40g (1 scoop)and reperfusion injury in rats; both carvacrol and silymarin Carvacrol was shown to be hepatoprotective against ischemia Action Ingredient Dose had similar beneficial effects on AST and ALT levels (Canbek 2007). Carvacrol also increased liver regeneration rate in rats Rebuild Whey protein isolate (Uyanoglu (bovine milk) 2008).

6.6g Also available in a plant-based formula after partial hepatectomy Pisum sativum: Yellow pea protein isolate activrecover+ Mutagenicity studies of carvacrol show only weak activity; carvacrol is excreted in urine after 24 hours in large quantities, unchanged or sativum: as glucoronide and sulphate Pisum Yellow pea protein isolate conjugates (De Vincenzi 2004).

Solanum tuberosum: Potato tuber protein isolate plant-based

activrecover+ References

Pisumsativum: pea protein isolate Canbek M, Uyanogluyellow M, Bayramoglu G, Senturk H, Erkasap5.7g N, Koken T, Uslu S, Demirustu C, Aral E, Husnu Can Baser K. Creatine monohydrate 2.0g Effects ofL-leucine carvacrol on defects of ischemia-reperfusion in the rat liver. Phytomedicine. 2008 Jan. 1.0g De Vincenzia M et al.

Constituents of aromatic plants: carvacrol.

L-isoleucine 500mg Fitoterapia 2004; 75(7-8): 801-804.

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

500mg Lambert L-glutamine RJ, Skandamis PN, Coote PJ, Nychas GJ. A study of500mg the minimum inhibitory concentration and mode of action of Re-Energize Zea mays fruit: 9.5g oregano essential oil, D-glucose thymol and carvacrol. J Appl Microbiol.

2001 Sep;91(3):453-62.

Oryza sativa: whole grain sprouted brown rice dry syrup 7.9g Pizzimenti FC, Cioni PL, Procopio F, Blanco AR. Effects of Nostro A, Roccaro AS, Bisignano G, Marino A, Cannatelli MA, sinensis: sweet orange fruit powder 4.0g oregano, Citrus carvacrol and thymol on Staphylococcus aureus and Staphylococcus epidermidis biofilms. J Med Microbiol.

Restore Aloysiacitrodora: lemon verbena leaf 600mg 2007;56(Pt 4):519-23.

Prunuscerasus: tart cherry fruit skin 100mg Nostro A et al. Susceptibility of methicillin-resistant staphylococci to oregano essential oil, carvacrol and thymol. FEMS Microbiol Lett. 2004;230(2):191-5.

References et al. J IntSocSports Nutr. 2010 May 7;7:17. of theKS, essential oil of Origanum virens on Candida species.

Salgueiro LR et al. Chemical composition and antifungal activity Kuehl Beelen M, et Med. al. Int J2003 Sport Sep;69(9):871-4.

NutrExercMetab. 2010 Dec;20(6):515-32.

Lagranha CJ, et al. Amino Acids. 2008 Apr;34(3):337-46.

Planta Connolly DA, et al. Br J Sports Med. 2006 Aug;40(8):679-83.

Lemon PW, et al. Can J ApplPhysiol. 1997 Oct;22(5):494-503.

Santoyo Cavero S, Jaime L, Ibañez E, Señoráns FJ, Reglero G. Supercritical dioxide extraction ofSuppl):S384-90. compounds with Cooper R, et al.S,J IntSoc Sports Nutr. 2012 Jul 20;9(1):33.

Lightfoot A, et carbon al. Crit Care Med. 2009 Oct;37(10 antimicrobial L.: determination of optimal extraction J Food Prot.

Cury-Boaventura MF,activity et al. Eur from J ApplOriganum Physiol. 2008vulgare Jun;103(3):289-94.

Paddon-Jones D, et al. Amparameters.

J ClinNutr. 2008 May;87(5):1558S-1561S. Fulgoni VL, et al. Am J ClinNutr. 2008 May;87(5):1554S-1557S. Shimomura Y, et al. Int J Sport NutrExercMetab. 2010 Jun;20(3):236-44.

2006;69(2):369-75.

Funes L, et al. EurM, J Appl Physiol.

Veggi K FT,upon et al. Int 23. [Epub ahead of Uyanoglu Canbed M,2011 AralApr;111(4):695-705.

E, Husnu Can Baser K. Effects of carvacrol theJ Sport liver NutrExercMetab.2013 of rats undergoingJan partial Howatson G, et al. J IntSoc Sports Nutr. 2012 May 8;9(1):20. print] hepatectomy. Phytomedicine 2008; 15(3): 226-9. ihpSept10_NAHS_Ad.indd 2 058.IHP NAHS mono.indd 1 IHPAPR2012_XXXX_ADVERTISER_Product_FP.indd 2

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InflaCalm SAP PRODUCT MONOGRAPH

INFLAMMATION & EICOSANOID SYNTHESIS

The inflammatory leukotrienes (LT) and prostaglandin 2‑series (PG2) of inflammatory mediators are dependent on the enzymes phospholipase‑A2, 5‑lipoxygenase (5‑LOX) and the cyclooxygenase (COX) complex (COX‑1 and COX‑2), and their major substrate is arachidonic acid.

It is well‑established and generally accepted that modulating the prostaglandin balance to favor the PG1 and PG3 series over PG2 reduces inflammation and may be used to mitigate pain. Increasing plant sources of essential fatty acids containing alpha‑linoleic and alpha‑ linolenic acids (flax seed, hemp, pumpkin seeds, borage, evening primrose, blackcurrant), as well as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oils, while decreasing the intake of arachidonic acid from animal meats should be a consideration in any anti‑inflammatory protocol.

Many pharmaceutical options, such as nonsteroidal anti‑inflammatory drugs (NSAIDs) and corticosteroids, exist that are capable of inhibiting the COX, LOX and phospholipase‑A2 enzymes, respectively. However, they are associated with a myriad of unwanted side effects, including increased gastrointestinal permeability and damage, increased risk of cardiovascular events, impaired tissue repair and wound healing, adrenal dysfunction and hormonal imbalances, impaired growth and development, and blood‑thinning effects. Botanical options and proteolytic enzymes may be as effective as pharmaceutical treatments, may be more cost‑effective, and may be safer for some populations.

BOSWELLIA, CURCUMIN, QUERCETIN AND PIPERINE

Boswellia (Boswellia serrata) and curcumin (from the turmeric spice, Curcuma longa) have been used historically in Ayurvedic medicine for the treatment of rheumatic and inflammatory conditions. Primary efficacy for the treatment of pain and inflammation with boswellia is attributed to the boswellic acids, which are selective and potent inhibitors of 5‑LOX.(1) Historically, the common preparations of boswellia may contain minimal or varying boswellic acid content.

InflaCalm SAP contains boswellia extract standardized to 70% boswellic acids.

Curcumin is a potent antioxidant and has been shown to inhibit both COX and 5‑LOX, reducing PG2 and LT in both in vitro and in vivo studies.(1) In postoperative patients, oral curcumin has been shown to be as effective as NSAIDs for controlling inflammation at daily doses of 1200 mg/d without side effects. Curcumin is extremely safe and non‑toxic, but should be considered contraindicated in biliary duct obstruction.(1, 2) Oral bioavailability and absorption of curcumin has long been a concern and its administration criticized, despite its clinical efficacy.(3) Human studies have now shown that concomitant administration of piperine can increase curcumin bioavailability by 2000% and absorption by over 22%, while significantly increasing its half‑life in the body.(2, 3) Quercetin is a bioflavonoid found in many plants and vegetables, and is known to inhibit phospholipase‑A2, 5‑LOX and the COX enzymes, as well as the production of the PG2 series, TNF‑α, nitric oxide and nitric oxide synthase,(1, 4, 5) all factors in inflammation, injury and pain. Quercetin bioavailability may be enhanced by concomitant administration of bromelain.(6)

BROMELAIN, TRYPSIN AND RUTIN

Bromelain is sourced from the pineapple (Ananas comosus) stem.

Bromelain is a proteolytic enzyme which has received a wealth of attention in the scientific literature for its anti‑inflammatory and

For more information visit: www.nfh.ca

IHP 2013-07 (InflaCalm SAP).indd 2 IHPAPR2012_XXXX_ADVERTISER_Product_FP.indd 2

fibrinolytic activities, as well as its ability to interfere with the growth of malignant cells and inhibit platelet aggregation. The use of bromelain is popular for the reduction of inflammation in arthritis, sports or musculoskeletal injuries, postsurgery recovery and wound healing, respiratory conditions, as a digestive aid, and in other inflammatory conditions.(1, 7) Bromelain promotes PG1 production and inhibits PG2 in a dose‑dependent manner and may exhibit more anti‑inflammatory action than prednisone.(1) Bromelain is also known to inhibit bradykinin formation and limit fibrin production.(7) Due to its potent effects on the prostaglandin systems, bromelain may theoretically have blood‑thinning and antithrombotic effects and interact with oral anticoagulants, but this has not yet been shown in human studies.(1, 7) The oral combination of bromelain, the proteolytic enzyme trypsin, and the bioflavonoid rutin has been well‑studied in humans in the literature,(8, 9) and specifically compared to diclofenac for the treatment of osteoarthritic hip pain.(8) Results of this double‑blind, randomized study showed equal efficacy compared to diclofenac for pain reduction, without the unwanted increased risk of negative effects of anemia and increase in liver enzymes. In a randomized controlled trial involving the comprehensive treatment of rotator‑cuff tendinitis in Canadian postal workers, the combination of bromelain, trypsin and rutin contributed to a statistically significant reduction of shoulder pain and increased quality of life compared to control.(9)

SERRATIOPEPTIDASE

Serratiopeptidase (also known as serrapeptase, serrapeptidase, or serratia peptidase) is a proteolytic enzyme derived from the nonpathogenic intestinal enterobacteria Serratia sp. E‑15, found in silkworms. Serratiopeptidase is known to have anti‑inflammatory effects as well as the ability to degrade insoluble proteins such as fibrin, and reduce the inflammatory mediator bradykinin. In human studies, serratiopeptidase efficacy for the reduction of pain and inflammation has been proven in various postsurgical conditions. A randomized, placebo‑controlled human trial demonstrated an improved response in dental postsurgical swelling and pain for serratiopeptidase (5 mg) when compared to paracetamol (1000 mg).(10) In rats, high doses of serratiopeptidase have been shown to be comparable to diclofenac in efficacy for both acute and chronic inflammation.(11)

REFERENCES 1.

Wallace, J.M. “Nutritional and botanical modulation of the inflammatory cascade— eicosanoids, cyclooxygenases, and lipoxygenases—as an adjunct in cancer therapy. “ Integrative Cancer Therapies 1, No. 1 (2002): 7–37.

2.

Suresh, D. and K. Srinivasan. “Tissue distribution & elimination of capsaicin, piperine & curcumin following oral intake in rats”. Indian Journal of Medical Research 131 (2010): 682–691.

3.

Shoba, G., et al. “Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers”. Planta Medica 64, No. 4 (1998): 353–356.

4.

Kelly, G.S. “Quercetin. Monograph”. Alternative Medicine Review 16, No. 2 (2011): 172–194.

5.

Xiao, X., et al. “Quercetin suppresses cyclooxygenase‑2 expression and angiogenesis through inactivation of P300 signaling”. PLoS One 6, No. 8: e22934.

6.

Thornhill, S.M. and A.M. Kelly. “Natural treatment of perennial allergic rhinitis”. Alternative Medicine Review 5, No. 5 (2000): 449–54.

7.

[No authors mentioned]. “Bromelain. Monograph.” Alternative Medicine Review 15, No. 4 (2010): 361–368.

8.

Klein, G., et al. “Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double‑blind, randomised study comparing oral enzymes with non‑steroidal anti‑inflammatory drugs”. Clinical and Experimental Rheumatology 24, No. 1: 25–30.

9.

Szczurko, O., et al. “Naturopathic treatment of rotator cuff tendinitis among Canadian postal workers: a randomized controlled trial”. Arthritis & Rheumatism 61, No. 8 (2009): 1037–1045.

10. Al‑Khateeb, T.H. and Y. Nusair. “Effect of the proteolytic enzyme serrapeptase on swelling, pain and trismus after surgical extraction of mandibular third molars”. International Journal of Oral Maxillofacial Surgery 37, No. 3 (2008): 264–268.

11. Jadav, S.P., et al. “Comparison of anti‑inflammatory activity of serratiopeptidase and diclofenac in albino rats”. Journal of Pharmacology & Pharmacotherapeutics 1, No. 2 (2010): 116–117. © NFH Nutritional Fundamentals for Health 2012

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InflaCalm SAP

Targeted nutraceutical therapy for pain management Prostaglandins are a class of hormone-like compounds called eicosanoids, which have biological activities in tissue repair and inflammation, amongst other actions. The prostaglandin 2-series (PG2) are known to be potent proinflammatory mediators synthesized by the cyclooxygenase (COX) enzymes, while the prostaglandin 1-series (PG1) and 3-series (PG3) have anti-inflammatory action.

Managing the balance of prostaglandins is a major aspect of mitigating pain and inflammation, and the modulation of the COX and other enzymes controlling the production of inflammatory mediators is the target of therapy. The components of InflaCalm SAP in synergistic combination maximize the delivery, absorption, and thereby anti-inflammatory effect of these well-researched nutraceuticals and herbs.

Each enteric-coated NON-GMO vegetable capsule contains:

ACTIVE INGREDIENTS

Bromelain (2400 GDU/g) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 mg Curcumin extract (95% curcuminoids) . . . . . . . . . . . . . . . . . . . . . . . 150 mg Quercetin dihydrate 98% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 mg Rutin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 mg Trypsin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 mg Boswellia serrata (70% boswellic acids). . . . . . . . . . . . . . . . . . . . . . . 100 mg Serratiopeptidase (2400 u/mg) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 mg Piper nigrum (black pepper) extract (95% piperine) . . . . . . . . . . . 1.5 mg Contains no: Preservatives, artificial flavor or color, sugar, dairy, starch, wheat, gluten, yeast, soy, citrus, corn or egg.

InflaCalm SAP is available in bottles of 90 or 180 enteric-coated capsules.

DOSAGE

Adults: Take 2 capsules once or twice daily or as directed by your health care practitioner.

INDICATIONS

ɶ InflaCalm SAP may be used in the treatment of acute and chronic pain. ɶ InflaCalm SAP may be used in the treatment of musculoskeletal injuries. ɶ InflaCalm SAP may be used to enhance postsurgical recovery and wound healing. ɶ InflaCalm SAP may be considered for use in the adjunctive treatment and prevention of chronic inflammatory disorders.

To maximize anti-inflammatory action, InflaCalm SAP may be combined with the Trident SAP line of omega-3 fatty acids from fish oil.

CAUTIONS

Do not use if you are pregnant or breast-feeding; or if you are taking blood thinning medication, antibiotics, or sedatives. Consult a health care practitioner prior to use if you are taking antiplatelet medication; if you have gallstones or a bile duct obstruction; or if you have stomach ulcers or excess stomach acid.

PURITY, CLEANLINESS AND STABILITY

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

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

Nutritional Fundamentals for Health • 3405 F.-X.-Tessier, Vaudreuil, QC J7V 5V5 • Tel. 1 866 510 3123 • Fax. 1 866 510 3130 • www.nfh.ca

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Stay T A S Hydrated T I N G // P E A K P E R F O R • Vitally important electrolytes from coconut potassium ensure proper hydration throug

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Stay Hydrated • Vitally important electrolytes from coconut

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P E R F O R M A N C E P E A K // TA S T I N G G R E AT // N AT U R A L A L L