IHP April 2014

HPA axis in Affective Disorders

Blood Donation

Natural Eggshell Membrane

By William R Ware, PhD

By Chris Habib, ND

PM42684014 | 60 BLOOR STREET WEST SUITE 1106 | TORONTO ONTARIO, M4W 3B8

IHP April/May 2014 | $14.95

By Tanya Lee, ND

Dr Meer Janjua, MD Clinic One - Winnipeg

Continuing Education: Acetyl-L-Carnitine and Depression

By Rochelle Fernandes, MSc, ND(cand)

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1. NHPD Abbreviated Labelling Standard – Live Microorganisms. August 30, 2011

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GENESTRA BRANDS HMF MULTI STRAIN PRODUCT MONOGRAPH HMF Multi Strain is a maintenance probiotic supplement formulated with 16 probiotic strains. The preparation includes 4 human-derived strains Lactobacillus acidophilus (CUL-60 & CUL-21), Bifidobacterium bifidum and Bifidobacterium animalis subsp. lactis and has been tested in various human clinical trials. Human strains have been shown to provide strong epithelial adherence with the ability to maintain a high tolerance to stomach acid. With 15 billion CFU per dose, each capsule is 100% pure vegetable-sourced, making it an excellent source of probiotics for vegans.

Human-derived Strains & Healthy Gastrointestinal Function: There is convincing evidence that probiotic supplementation helps prevent the recurrence of C. difficile. A study observed a test group of (150) receiving antibiotic therapy randomised to receive either a probiotic containing both Lactobacillus and Bifidobacterium or a placebo for 20 days. Each patient received one capsule/day for 20 days. The probiotic product (provided by Cultech, Swansea) comprised 2 x 1010 CFU Lactobacillus acidophilus and Bifidobacterium bifidum/capsule; the placebo comprised the inactive carrier. Toxin testing of C. difficile-positive patients indicated that five of the 11 probiotic patients (46%) were toxin-positive with two of the five toxin-positive patients showing signs of diarrhoea. Seven of the nine placebo patients carrying C. difficile (78%) were toxin-positive, and six of these seven had diarrhoeal symptoms.1 Probiotics & Proper Immune Function: The microbiota ensures intestinal structure and function and the homeostasis of the gut microbiota also maintains various functions, which are vital to the maintenance of human health. In fact, disruption of the intestinal ecosystem equilibrium is associated with a plethora of human diseases, including autoimmune, allergic reactions and bacterial infections.2 The use of probiotics stimulates gut reaction by producing vitamins, synthesizing amino acids and carrying out biotransformation of bile. Probiotics help create a defensive barrier within the host as they compete with other microorganisms for attachment sites in epithelial cells.3 Probiotics & Western Culture: Westernization has significantly altered our microbial function. Studies have shown that a westernized diet rich in animal proteins and low in complex carbohydrates, plus the overuse of antibiotics and underuse of breastfeeding, can lead to a heightened inflammatory response of the microbiota.4

EACH CAPSULE CONTAINS: Probiotic Consortium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 billion CFU Lactobacillus acidophilus (CUL-60) Lactobacillus acidophilus (CUL-21) Bifidobacterium bifidum (CUL-20) Bifidobacterium animalis subsp. lactis (CUL-34) Lactobacillus salivarius (CUL-61) Lactobacillus paracasei (CUL-08) Lactobacillus plantarum (CUL-66) Lactobacillus casei (CUL-06) Lactobacillus fermentum (CUL-67) Lactobacillus gasseri (CUL-09) Bifidobacterium animalis subsp. lactis (CUL-62) Bifidobacterium breve (CUL-74) Streptococcus salivarius subsp. thermophilus (CUL-68) Lactobacillus acidophilus (NCFM™) Bifidobacterium animalis subsp. lactis (HN019) Lactobacillus rhamnosus (HN001) Non-Medicinal Ingredients: Hypromellose, cellulose, silica

Recommended Dose: Adults, Adolescents and Children (6 years and older): Take one capsule daily, at least two to three hours before or after taking antibiotics, or as recommended by your healthcare practitioner Guaranteed to contain no added wheat, starch, gluten, soy, artifical colouring or flavouring, antimicrobial preservatives, dairy or animal products. Ideal for vegans.

1. Plummer, S., Weaver, M.A., Harris, J.C., Dee, P. and Hunter, J. “ Clostridium difficile pilot study: effects of probiotics supplementation on the incidence of C.difficile diarrhea.” International Microbiology. 2004; 7(1):59-62.

2. Prakash S, Rodes L, Coussa-Charley M, Tomaro-Duchesneau C. Gut microbiota: next frontier in understanding human health and development of biotherapeutics. Biologics. 2011;5:71-86.

3. Probiotics & Immunity Journal of Gastroentology, A.T. Borchers et al.: Probiotics and immunity 4. Greer JB, O’Keefe SJ. Microbial induction of immunity, inflammation, and cancer. Front Physiol. 2011 Jan 26;1:168.

C ANADA: 1-800-263-5861 | www.seroyal.com

from the publisher

Connect With Us

2014 is in full swing!

W

ith a cold and long winter behind us, we look forward to the busy spring that lies ahead! The annual Primary Care event is just around the corner, an opportunity to showcase the best of the natural health products industry to the ever- growing list of interested conventional healthcare providers. Likewise we find ourselves getting ready for the annual American Association of Naturopathic Physicians conference, returning to the beautiful Biltmore resort in Arizona. We look forward to seeing you at these important events!

Our website has undergone a much- needed makeover... We encourage you to check it out and let us know your thoughts!

An archive of all past IHP feature articles, continuing education articles, cover stories, clinic profiles, and news has been made available... We trust you will find it useful.

Sanjiv Jagota Publisher

4 www.ihpmagazine.com l April/May 2014

Products Professionals Prefer®

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Hepato DR® Liver Tonic and Detoxifier

Product Monograph for IHP, April/May 2014

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 water-soluble 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.

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

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

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

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.

Proven clinically effective during more than 20 years of use, Hepato DR® has garnered glowing reports nation-wide from everyday users and healthcare practitioners alike. One Vancouver area naturopathic physician, for example, testifies that: “I have been a student of health and healing since the early seventies and have found your products to be truly the best. To this day nothing compares to your quality. I have been using Hepato DR® for years as a liver cleanser with great results.”

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Products Professionals Prefer®

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Integrated Healthcare

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

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

Advertising Information Sanjiv Jagota | Tel: (416) 203-7900 ext 6125 Email: sanjiv@ihpmagazine.com Jeff Yamaguchi | Tel: (416) 203-7900 ext 6122 Email: jeff@gorgmgo.com 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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• Highly bioavailable pure curcumin • Offers the best ratio of bioavailable to total curcumin • 5 times more bioavailable than soy lecithin based curcumin • Soy, Gluten and Dairy Free

Published by IHP Magazine Canada Post Canadian Publication Mail Agreement Number 4067800 The publisher does not assume any responsibility for the contents of any advertisement and any and all representations or warranties made in such advertising are those of the advertiser and not of the publisher. The publisher is not liable to any advertiser for any misprints in advertising not the fault of the publisher and in such an event the limit of the 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, 0electronic, internet, disc, etc.) without the consent of, or the payment of compensation to, the party providing such material. Please direct submissions to the Editor, ihp magazine.

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contents

This Issue: April/May 2014 • Vol. 7 • No. 2

32 Clinic One

Cover Story Clinic One is an innovative health care center located in the heart of Winnipeg’s exchange district.

40 Living Well Integrative Health Center Clinic Profile

Collaboration On The East Coast

44 The Journal of IHP

Peer-reviewed articles on clinically revelant topics

Coming Next Issue Chemotherapy- induced neuropathy

Departments

4 Publisher’s Letter 11 Research News 19 Industry News 24 Calendar 27 Product Profiles 45 Editor’s Letter 47 Peer Review Board 49 Editorial Board 73 Continuing Education:

Genetic screening - fertility medications

Acetyl-L-carnitine for depression and mood disorders

The physiology of menopause

By Rochelle Fernandes, MSc, ND (cand)

Cover Photograph by Hart Macklin

8 www.ihpmagazine.com l April / May 2014

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

RevitalAge™ Ultra Supports Youthful Gene Expression

Mitochondrial Renewal

Healthy Aging

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

Under license from

Inc.

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

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

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

RevitalAge Ultra ™

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

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

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

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

What Is The Source?

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

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

RevitalAge™ Ultra three vegetable capsules contain

v 00

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

3 capsules daily, with meals. †Under

license from

Inc.

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

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

Inflammationassociated pigmentation in psoriasis mediated by IL-17 and TNF

research news EGFR mutations in Asian patients with non-smallcell lung cancer

The etiology of the underlying inflammation-associated pigmentation changes in psoriasis was studied in this article. Previously, it was unclear how the myriad of cytokines known to be involved in inflammatory skin processes affect epidermal melanocytes.

The authors sought to determine how IL-17 and tumor necrosis factor (TNF) influence normal human melanocytes, as these two cytokines have been implicated in various skin diseases. IL-17 and TNF jointly stimulated broad inductions of cytokines, including melanoma mitogens CXCL1 and IL-8.

Moreover IL-17 and TNF synergistically inhibited pigmentation-related signaling and melanin production, and induced keratinocyte production of β-defensin 3, an antagonist for melanocortin 1 receptor. When analyzing psoriasis lesions that are known to overexpress IL-17 and TNF, the authors observed an increase in melanocyte number and a simultaneous decrease in pigmentation signaling. Furthermore, therapeutic neutralization of TNF and IL-17 with mAbs resulted in a rapid recovery of pigment gene expression in psoriasis lesions. They conclude that IL-17 and TNF can affect both the growth and pigment production of melanocytes, which may contribute to the pigmentation changes associated with psoriasis. These findings may allow the development of novel therapeutics for pigmentary disorders and bring new insights into the immune milieu surrounding melanocytes and related neoplasms. J Invest Dermatol. December 2013. PMID: 23732752

Known as the PIONEER trial, this study was a prospective, multinational, epidemiological study of epidermal growth factor receptor (EGFR) mutations in patients from Asia with newly diagnosed advanced lung adenocarcinoma.

Eligible patients had untreated stage IIIB/IV adenocarcinoma. EGFR mutation status of tumor samples was determined. The results showed that of 1482 patients from seven Asian regions, 43.4% of patients were female, median age was 60 years (range, 17-94), and 52.6% of

Nutrition and pancreatic cancer

patients were never-smokers. EGFR mutation status was evaluable in tumors from 1450 patients (97.8%) (746 [51.4%] positive; 704 [48.6%] negative). Country, sex, ethnicity, smoking status, pack-years (all p < 0.001), disease stage (p = 0.009), and histology type (p = 0.016) correlated significantly with EGFR mutation frequency. Mutation frequency was 61.1% in females, 44.0% in males; lower in patients from India (22.2%) compared with other areas (47.2%64.2%); highest among neversmokers (60.7%); and decreased as pack-year number increased (>0-10 pack-years, 57.9%; >50 pack-years, 31.4%) (similar trend by sex).

Ethnic group (p < 0.001) and packyears (p < 0.001) had statistically significant associations with mutation frequency (multivariate analysis); sex was not significant when adjusted for smoking status. The authors conclude that there is high EGFR mutation frequency (51.4% overall) in tumors from Asian patients with adenocarcinoma. J Thorac Oncol.

February 2014. PMID: 24419411.

This review evaluated the role of dietary components in pancreatic cancer. Pancreatic cancer has a poor prognosis with a 5-year survival rate of less than 5%. The authors performed searched in PubMed using the terms “pancreatic cancer”, together with “nutrition”, “diet”, “dietary factors”, “lifestyle”, “smoking”, “alcohol” and “epidemiology”. The results showed that fruits, particularly citrus, and vegetable consumption may be beneficial.

The consumption of whole grains has been shown to reduce pancreatic cancer risk and fortification of whole grains with folate may confer further protection.

Red meat, cooked at high temperatures, should be avoided, and replaced with poultry or fish. Total fat should be reduced. The use of curcumin and other flavonoids should be encouraged in the diet. There is no evidence for benefit from vitamin D supplementation. There may be benefit for dietary folate.

Smoking and high Body Mass Index have both been inversely associated with pancreatic cancer risk. The authors conclude that there is evidence to encourage the use of whole grain in the staple diet and supplementation within the diet of folate, curcumin and other flavanoids. Carefully designed randomized trials are required to further elucidate these important matters.

Anticancer Res. January 2014. PMID: 24403441

April/May 2014 l www.ihpmagazine.com 11

research news Biomarkers and receptor targeted therapies reduce risk in non-small cell lung cancer This study analyzed the risk of clinical trial failure during non-small cell lung cancer (NSCLC) drug development.

NSCLC drug development was investigated using publically available resources. Analysis was conducted in regard to treatment indication, compound classification, and mechanism of action. The results showed that six hundred seventy-six clinical trials that included 199 unique compounds met the inclusion criteria. The likelihood, or cumulative clinical trial success rate, that a new drug would pass all phases of clinical testing and be approved was found to be 11%, which is less than industry aggregate rates. Over half of the biomarkers used in NSCLC have not yet been approved by the Food and Drug Administration in any indication. Biomarker targeted therapies (62%) and receptor targeted therapies (31%) were found to have the highest success rates. The risk-adjusted cost for NSCLC clinical drug development was calculated to be U.S. $1.89 billion. The authors conclude that biomarker use alone in this indication results in a six-fold increase in clinical trial success whereas receptor targeted therapies did so by almost threefold. Physicians who enroll patients in NSCLC trials should prioritize their participation in clinical trial programs that use biomarkers and receptor targeted therapies. J Thorac Oncol. February 2014. PMID: 24419412

Neurobehavioural effects of developmental toxicity This review article discusses industrial chemicals as causes of developmental neurotoxicity.

Neurodevelopmental disabilities, including autism, attention-deficit hyperactivity disorder, dyslexia, and other cognitive impairments, affect millions of children worldwide, and some diagnoses seem to be increasing in frequency. Industrial chemicals that injure the developing brain are among the known causes for this rise in prevalence. In 2006, the authors did a systematic review and identified five industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls, arsenic, and toluene.

Since 2006, epidemiological studies have documented six additional developmental neurotoxicantsâ&#x20AC;&#x201D; manganese, fluoride, chlorpyrifos, dichlorodiphenyltrichloroethane, tetrachloroethylene, and the polybrominated diphenyl ethers.

The authors postulate that even more neurotoxicants remain 12 www.ihpmagazine.com l April/May 2014

undiscovered. To control the pandemic of developmental neurotoxicity, they propose a global prevention strategy. Untested chemicals should not be presumed to be safe to brain development, and chemicals in existing use and all new chemicals must therefore be tested for developmental neurotoxicity.

To coordinate these efforts and to accelerate translation of science into prevention, the authors propose the urgent formation of a new international clearinghouse. The Lancet Neurology. March 2014.

PMID: N/A\

Impact of brief CBT for insomnia on health care utilization and costs This trial examined health care utilization (HCU) and costs following brief cognitive behavioural treatment for insomnia (bCBTi). The authors reviewed medical records of outpatients treated in a behavioural sleep medicine clinic based in an accredited sleep disorder center.

Six indicators of HCU and costs

were obtained: estimated total and outpatient costs, estimated primary care visits, CPT costs, number of office visits, and number of medications. All patients completed more than 1 session of bCBTi. Those who attended greater than 3 were considered completers and completers with significant sleep improvements were considered responders. The results showed that for both completers and responders, all HCU and cost variables, except number of medications, significantly decreased or trended towards decrease at post-treatment.

Completers had an average decrease in CPT costs of $200 and estimated total costs of $75. Responders had average decreases in CPT costs of $210. The authors conclude that bCBTi can reduce HCU and costs.

Response to bCBTi resulted in greater reduction of HCU and costs.

The findings highlight the need for greater dissemination of bCBTi for several reasons: a high percentage of completers responded to treatment, as few as 3 sessions can result in significant improvements insomnia, and bCBTi can be delivered by novice clinicians. J Clin Sleep Med. February 2014. PMID: 24532995

PROGRESSIVE NUTRITIONAL THERAPIES VEGESSENTIAL ALL IN ONE VegEssential™ combines the benefit of an entire cupboard full of supplements with the ease of consuming a single smoothie. This simple to use all-in-one formula not only provides unmatched nutritional density, it also provides unmatched convenience.

VegEssential™ embraces the wisdom of consuming an alkaline-forming, whole-food diet and draws on almost 100 plant-based ingredients to deliver an incredible spectrum of both micro and macro nutrients.

Vegetable protein intake was inversely related to blood pressure. This finding is consistent with recommendations that a diet high in vegetable products be part of healthy lifestyle for prevention of high blood pressure and related diseases (Elliot, et al 2006).

Elderly women with a high dietary ratio of animal to vegetable protein intake have more rapid femoral neck bone loss and a greater risk of hip fracture than do those with a low ratio. This suggests that an increase in vegetable protein intake and a decrease in animal protein intake may decrease bone loss and the risk of hip fracture (Sellmeyer, et al 2001).

An elevated level of total plasma homocysteine (tHcy) is considered to be a predictor of the mortality risk for all diseases. Panunzio et al (2003) investigated whether supplementation of concentrated fruit and vegetables is able to decrease tHcy levels. Twenty-six subjects participated in a cross-over design intervention trial, receiving 2 capsules of fruits and 2 capsules of vegetables a day for 4 weeks, then acting as his/her own control for another 4 weeks. It was revealed that plasma tHcy concentration was decreased as a result of taking a powdered fruit and vegetable extract on a daily basis, reducing a risk factor causally linked to chronic disease.

Cao et al (1998) examined whether a diet rich in fruit and vegetables would affect the antioxidant capacity of human plasma. Thirty-six healthy nonsmokers consumed 2 sets of control diets providing 10 servings of fruits and vegetables each day (for 15 days) with or without an additional 2 servings of broccoli each day on days 6-10. It was observed that increased consumption of fruit and vegetables could increase the plasma antioxidant capacity in humans.

Vazir, et al (2006) evaluated the effect of a micronutrient supplement on mental function in children (aged 6 – 15 years). This double blind, placebo-controlled, matched-pair, cluster, randomized trial assessed a cohort of 608 children for intelligence, attention and concentration, memory, and school achievement, before and after 14 months of micronutrient supplementation. Results indicated that supplementation with a range of micronutrients significantly improved attention-concentration over the period of 14 months in children aged 6 – 15 years.

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

Dosage Indication: A factor in the maintenance of good health.

Adults (≥ 18 years)

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

Interactions There is insufficient research available regarding the safety of several of the herbal components in children, as a result the use of VegEssential is not recommended in children under 18 years of age (Jellin et al (2006)).

Due to the potential of toxicity and adverse effects of some of the constituents, VegEssential is not recommended for use in pregnant or breastfeeding women (Jellin et al (2006)).

Some the components in VegEssential may interact with medication, diseases and conditions, and/or lab test results. It is recommended that all ingredients be reviewed before use in an individual under medical supervision, taking prescription medication, suffering from a serious and/or pre-existing medical condition (Jellin et al (2006)).

Quality Assurance

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

Test

Specifications

USP USP USP USP USP

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

USEPA USEPA USEPA USEPA

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

USP USP

Absent Conforms to limits

References Cao G, et al (1998). Increases in human plasma antioxidant capacity after consumption of controlled diets high in fruit and vegetables. Am J Clin Nutr, 68: 1081-1087.

Elliott P, et al. Association Between Protein Intake and Blood Pressure: The INTERMAP Study. Arch Intern Med, Jan 2006; 166: 79 - 87

Holmquist C, et al (2003). Multivitamin Supplements Are Inversely Associated with Risk of Myocardial Infraction in Men and Women – Stockholm Heart Epidemiology Program (SHEEP). J Nutr, 133: 2650-2654.

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

Sellmeyer, D. E., et al. 2001. A high ratio of dietary animal to vegetable protein increases the rate of bone loss and the risk of fracture in postmenopausal women. American Journal of Clinical Nutrition. 73(1): 118-122.

Panunzio MF, et al (2003). Supplementation with fruit and vegetable concentrate decreases plasma homocysteine levels in a dietary controlled trial. Nutrition Research, 23: 1221-1228.

Vazir S, et al (2006). Effect of micronutrient supplement on health and nutritional status of schoolchildren: mental function.

Nutrition, 22: S26-S32.

research news Grade seed extract decreases mucositis in rat model, enhancing chemotherapy The authors investigated the effects of increasing grape seed extract doses on the severity of chemotherapy in a rat model and its coincident impact on chemotherapeutic effectiveness in colon cancer cells. Female Dark Agouti rats were gavaged with grape seed extract (400–1000 mg/kg) or water (day 3–11) and were injected intraperitoneally with 5-Fluorouracil (150 mg/kg) or saline (control) on day 9 to induce mucositis. Daily metabolic data were collected and rats were sacrificed on day 12. Intestinal tissues were collected for histological and myeloperoxidase analyses.

Caco-2 cell viability was examined in response to grape seed extract in combination with 5-Fluorouracil by 3-(4,5-Dimethylthiazol-2yl)-2,5diphenyl-tetrazoliumbromide) assay.

The results showed that compared with 5-Fluorouracil controls, grape seed extract (400–1000 mg/ kg) significantly decreased the

Intervention to reduce obesity and menopausal symptoms in women

histological damage score (P<0.05) in the jejunum. Grape seed extract (1000 mg/kg) increased jejunal crypt depth by 25% (P<0.05) in 5-Fluorouracil treated rats compared to 5-Fluorouracil controls, and attenuated the 5-Fluorouracil -induced reduction of mucosal thickness (25%, P<0.05). Grape seed extract (600 mg/kg) decreased myeloperoxidase activity by 55% (P<0.01) compared to 5-Fluorouracil controls. The authors conclude that grape seed extract may represent a new therapeutic option to decrease the symptoms of intestinal mucositis while concurrently impacting on the viability of colon cancer cells. PLoS One. January 2014. PMID: 24465501

This study was performed to determine whether a personalized sex-specific intervention, WAIPointes (WAI stands for Who Am I), could reduce central obesity in women undergoing perimenopausal transition. Eighty-three of 103 women aged 35 to 55 years and experiencing symptoms of the menopausal transition completed a 6-month WAIPointes demonstration project; 75 consented to data review.

Sex-specific history was obtained on visit 1; directed physical examination for body mass index, body fat percentage, waist circumference, and blood pressure were performed at each of four or five subsequent

Review of internal genes of modern avian influenza virus shows global sweep in late 1800’s This review identifies factors that mediate the emergence of RNA viruses such as influenza A virus (IAV). Phylogenetic inference is crucial to reconstructing the origins and tracing the flow of IAV within and between hosts. The authors show that explicitly allowing IAV host lineages to have independent rates of molecular evolution is necessary for reliable phylogenetic inference of IAV and that methods that do not do so, including ‘relaxed’ molecular clock models, can be positively misleading. A phylogenomic analysis using a hostspecific local clock model recovers extremely consistent evolutionary histories across all genomic segments and demonstrates that the equine H7N7 lineage is a sister clade to strains from birds-as well as those from humans, swine and the equine H3N8 lineage-sharing an ancestor with them in the mid to late 1800s.

On the basis of these phylogenies and the synchrony of these key nodes, we infer that the internalgenes of avian influenza virus (AIV) underwent a global selective sweep beginning in the late 1800s, a process that continued throughout the twentieth century and up to the present. The resulting western hemispheric AIV lineage subsequently contributed most of the genomic segments to the 1918 pandemic virus and, independently, the 1963 equine H3N8 panzootic lineage. Nature. February 2014. PMID: 24531761.

monthly visits. Other tests were ordered as necessary to determine risk stratification. Participants were assessed for menopause status, and they reported activity and menopausal symptoms at each visit. Personalized strategies for health improvement were developed in partnership.

Women served as their own controls.

Data from visit 2 were compared with data from visit 4. The results showed that the intervention reduced waist circumference and diastolic blood pressure and improved self-reported menopausal symptoms and physical activity levels. The authors conclude that the WAIPointes program offers potential as an effective officebased clinical intervention to reduce cardiovascular risk factors and symptoms of menopause in women during the menopausal transition.

Menopause. February 2014. PMID: 24518150 April/May 2014 l www.ihpmagazine.com 15

research news

This study used the Florida birth registry data to investigate the associations between air pollutants (NO2, SO2, PM(2.5), O3 and CO) and the risks of HDP in 22,041 pregnant women in Jacksonville, Florida, USA from 2004 to 2005.

The authors examined whether air pollution exposure during different time windows defined by trimesters and the entire pregnancy had different effects on HDP.

The single-pollutant logistic regression model showed that exposure to four pollutants during the full pregnancy period was significantly associated with prevalence of HDP after adjusting for covariates: NO2 (OR=1.21, 95% CI 1.09 to 1.35), PM2.5 (OR=1.24, 95% CI 1.08 to 1.43), SO2 (OR=1.13, 95% CI 1.01 to 1.25) and CO (OR=1.12, 95% CI 1.03 to 1.22) per IQR increase. Similar effects were observed when first trimester exposure to NO2, SO2 and CO, and second trimester exposures to PM2.5 were examined. Consistent results were confirmed in multiple-pollutant models. The authors conclude that exposure to high levels of air pollution during early pregnancy and the full gestational period was associated with increased prevalence of HDP in Florida, USA. J Epidemiol Community Health. January 2014.

PMID: 24022815

16 www.ihpmagazine.com l April/May 2014

Regulation of the catabolic cascade in OA by zinc In this study, the authors examined the catabolic cascade in osteoarthritis (OA). OA is primarily characterized by cartilage degeneration, is caused by an imbalance between anabolic and catabolic factors. The authors investigated the role of zinc (Zn(2+)) homeostasis, Zn(2+) transporters, and Zn(2+)-dependent transcription factors in OA pathogenesis. Among Zn(2+) transporters, the Zn(2+) importer ZIP8 was specifically upregulated in OA cartilage of humans and mice, resulting in increased levels of intracellular Zn(2+) in chondrocytes. ZIP8mediated Zn(2+) influx upregulated the expression of matrix-degrading enzymes (MMP3, MMP9, MMP12,

MMP13, and ADAMTS5) in chondrocytes. Ectopic expression of ZIP8 in mouse cartilage tissue caused OA cartilage destruction, whereas Zip8 knockout suppressed surgically induced OA pathogenesis, with concomitant modulation of Zn(2+) influx and matrix-degrading enzymes.

Furthermore, MTF1 was identified as an essential transcription factor in mediating Zn(2+)/ZIP8-induced catabolic factor expression, and genetic modulation of Mtf1 in mice altered OA pathogenesis. The authors conclude that the zinc-ZIP8-MTF1 axis is an essential catabolic regulator of OA pathogenesis. This could have potential implications when translated into the clinical setting. Cell.

February 2014. PMID: 24529376

Validation of metabolic syndrome score and prediction of cardiometabolic outcomes In this study, the authors validated the metabolic syndrome (MetS) score by confirmatory factor analysis (CFA) in children, middle-aged men, and older women and men and by investigating the relationships of the MetS score to incident type 2 diabetes, myocardial infarction, and

cardiovascular and overall death in middle-aged men. The results showed that second-order CFAs in which the MetS was represented by a second-order latent variable underlying four latent variables characterised by abdominal obesity, insulin resistance, dyslipidemia and raised blood pressure in different age groups. These second-order factors and factors derived from first-order CFA using previously proposed models were strongly associated with a composite MetS score in all age groups (r = 0.84-0.94) and similarly predicted type 2 diabetes, cardiovascular outcomes and mortality in middle-aged men. The risk of type 2 diabetes, myocardial infarction, cardiovascular death and overall death increased 3.67-, 1.38-, 1.56- and 1.44-fold, respectively, for a 1 SD increase in the MetS score.

The authors conclude that MetS can be described as a single entity in all age groups. The MetS score is a valid tool for research evaluating cardiometabolic risk in different age groups. Further research is needed to define cut-off points for risk estimation in clinical practice.

Diabetologia. January 2014. PMID: 24463933

Photos©iStockphoto.com

Ambient air pollution and hypertensive disorder of pregnancy

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

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

industry news Joint statement: Canadian health leaders call for better health workforce planning to enhance patient care In light of the growing employment challenges facing Canadian doctors and the impact on patient care, the Steering Committee of the National Physician Employment Summit is calling for action to help highly-trained doctors work to their capacity to meet the needs of the public. More than 100 representatives from Canada’s medical organizations, governments, medical educators, researchers, residents, medical students and physicians agreed that solutions must be developed to address the troubling number of unemployed and underemployed physicians countrywide. The root causes of this are multi-faceted, including limitations to our existing planning models, data on population needs, and learning environments that reflect patient needs. Positively, multiple groups across Canada are conducting research and analysis on this issue. Attendees strongly support the current work of the Physician Resource Planning Task Force (PRPTF), supported by the F/P/T Committee on Health Workforce, which brings key stakeholders from across medicine, academia, government, and learner organizations together to determine the right number, mix and distribution of physicians to meet societal needs. Participants advocated for sustainable funding to continue and expand this work.

CMA hitting the road to sound out Canadians on end-of-life issues The Canadian Medical Association (CMA) will be travelling across the country to find out what Canadians think about endof-life issues in a national dialogue. Dr. Louis Hugo Francescutti, CMA President, said today the goal is to engage and hear Canadians’ thoughts on physician-assisted dying, palliative care and advance care planning. “Most of the attention has been focused on the question of physician-assisted dying and we’re concerned the end-of-life debate is being oversimplified,’’ Dr. Francescutti said. “We need to hear more from Canadians about how their health care system can ensure not only a long, healthy life but also a good death.’’ The issue of end-of-life care has been an issue of major public importance, with political leaders such as Ontario Premier Kathleen Wynnecalling for a national dialogue. “I think it raises enormous questions, but I think it’s a national discussion,” Wynne said last summer. “I think it’s going to happen across the country.”

Launch of www.TerrorVictimResponse.ca As part of the Kanishka Project Contribution Program, a multi-year investment in terrorism-focused research funded by the Government of Canada, the Canadian Resource Centre for Victims of Crime (CRCVC) is launching a bilingual website for communities to utilize to help them prepare for and mitigate a terrorist attack or mass victimization event in Canada. TerrorVictimResponse.ca encourages communities to develop a comprehensive response plan which will positively impact the resiliency of victims, survivors and communities in the event of a terrorist incident on Canadian soil. One of the primary goals of TerrorVictimResponse.ca is to provide practical information to emergency response officials that can be implemented to help address the realities arising from a terrorist event. The Checklist for Communities incorporates the needs of victims and survivors at each stage of the response and recovery efforts. Reflective of events from around the world, the Checklist for Communities incorporates first-hand experiences of victims and survivors, as well as lessons learned by communities and responders who have experienced a terrorist event. Most importantly, the TerrorVictimResponse.ca website provides the only national web-based resource for emergency management, law enforcement and government officials who may be required to deliver tangible support to persons harmed. Ensuring that victims and survivors can recover and normalize their lives is critical in fostering community resilience. Communities must be prepared to meet the immediate, intermediate and long-term needs of victims and survivors of terrorist acts/mass victimizations and can do so by incorporating victims into their official response plans.

ARTERIA Program $49.2M investment for patients with or at risk of cardiovascular disease The Montreal Heart Institute (MHI) announced last week the launch of ARTERIA, a research program aimed at developing ground-breaking treatments for cardiovascular diseases, the number one cause of death worldwide. “Once again, the Montreal Heart Institute and its team of dedicated physicians, researchers and professionals have established themselves as world leaders in the fight against heart disease. This program will have tangible positive effects on patients living with or at risk of developing cardiovascular disease,” declared Dr. Jean-Claude Tardif, Director of the MHI Research Centre who will be leading the project. The discoveries and innovations that will stem from this unique program will substantially benefit patients over the medium and long term by transforming medical practices in the treatment of heart disease, all while realizing major savings for the health system as a whole. Among its many benefits, ARTERIA will make it possible to deliver increasingly personalized medicine and to treat and medicate patients more effectively, thus saving lives. It is noteworthy that cardiovascular diseases are the leading cause of hospitalization and deaths in the world, and that 1.3 million Canadians suffer from various forms of the illness. Cardiovascular diseases also represent the largest economic burden of all diagnostic categories with total annual costs of approximately $22 billion in Canada.

April/May 2014 l www.ihpmagazine.com 19

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CurcuVIVA is not just curcumin or turmeric. While 95% curcumin products are far better therapeutically than turmeric, curcumin is still renowned for being poorly absorbed, with large doses of up to 8 grams being needed to achieve therapeutic benefits (Cheng et al., 2001; Lao et al., 2006). Although many different “high-bioavailability” curcumin products are now available to the natural health industry, many of which have outrageous and unfounded bioavailability claims, the clinical studies behind Longvida® curcumin by far show the most promising results.

Although Longvida® curcumin demonstrated a 65-fold increase in bioavailability as determined by its CMax compared to regular curcumin, the AUC (area under the curve) actually showed more than a 100-fold increase (Gota et al., 2010). Just one capsule of CurcuVIVA delivers a therapeutically effective dose of curcumin, the equivalent of over 8g of a regular 95% curcumin extract. This would require taking 17 capsules of regular 95% curcumin extract, or more than 60 capsules of a 750mg turmeric root extract!

Bioavailability Mechanism Longvida Curcumin® consists of Solid Lipid Particles™ (SLP) which are tiny nano-sized (1 billionth of a meter) particles that have a protective layer providing a phenomenal increase in stability, potency and effectiveness. Unlike regular curcumin, SLP™ particles are resistant to gastric acid and intestinal alkalinity, absorbed rapidly through the intestinal lining and protected from phase II detoxification.

Unlike other so-called bioavailable curcumins, Longvida® curcumin then exists as free curcumin, not glucuronidated curcumin which does not pass through the blood-brain barrier. Finally, the tiny size of the nanoparticle allows it to be taken up into the body’s cells quickly to be put to use. This means that Longvida® curcumin delivers all of the health benefits of curcumin much more efficiently than any other curcumin product.

Therapeutic Potentials Clinical studies show that curcumin is highly effective for improving joint mobility and for reducing stiffness, swelling and pain. Curcumin’s main mechanism of action as an anti-inflammatory is through modulating the notorious NF-κB signaling. Curcumin is also a potent antioxidant and anti-microbial, and is cardioprotective. Additional recent studies have found that curcumin may be beneficial in HIV (Gandapu et al., 2011), chronic liver disease (Bischt et al., 2011), and even MS (Xie et al., 2011). The abundance of research points towards curcumin’s therapeutic potential in cancer, where it has been found to inhibit TNF-α, angiogenesis, metastasis, encourage cancer cell apoptosis and shrink tumors in some patients, help prevent relapse, and it has been used as adjunct therapy with radiation and certain forms of chemotherapy.

Curcumin has been seen as a very promising compound in the treatment and prevention of Alzheimer’s disease, based on in vitro work, but bioavailability problems have prevented clinical application (Belkacemi et al. 2011). The incredible increase in bioavailability of Longvida® curcumin compared to normal curcumin has made it possible to study the effect of curcumin on Alzheimer’s disease in vivo, and a human study using the equivalent of 400-600mg of Longvida® curcumin on Alzheimer’s patients is underway (Belkacemi et al., 2011). A new study led by Dr. DiSilvestro at the University of Ohio found increased clearance of serum beta-amyloid in healthy subjects after only 1 month taking 80mg of Longvida® curcumin, the same dose in CurcuVIVA. Imagine the potential results of longer-term supplementation!

CurcuVIVA is Safe & Effective Curcumin is therapeutically beneficial in many degenerative diseases. Longvida® curcumin has a phenomenal safety profile in both healthy individuals as well as in fragile populations such as cancer patients, and regular curcumin has shown no toxicity with up to 12 grams (Cheng et al., 2001; Lao et al., 2006; Gota et al., 2010; DiSilvestro et al., 2012). CurcuVIVA by AOR delivers a high dose of Longvida® curcumin, the most bioavailable curcumin on the market that is efficient in relieving pain and inflammation and protective against inflammatory-based conditions.

NPN: 80034713 Serving Size: Longvida® Optimized Curcumin* (from Curcuma longa root 25-30:1)

1 Capsule 80 mg

Non-medicinal ingredients: ascorbyl palmitate, soy lecithin, maltodextrin, microcrystalline cellulose, silicon dioxide, stearic acid.

Capsule: hypromellose. * LONGVIDA® is a registered trademark of Verdure Sciences Inc. International patent pending.

Adult Dosage: Take 1 capsule per day, or as directed by a qualified health care practitioner.

Caution: Consult a health care practitioner prior to use if you are pregnant, taking antiplatelet medication or blood thinners, or if you have gallstones, a bile duct obstruction, stomach ulcers or excess stomach acid. Consult a health care practitioner if symptoms persist or worsen.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

industry news Six Studies to Highlight Effectiveness of Spiritual Care in Health Care for People Facing Serious Illness Six groundbreaking studies will be presented at the HealthCare Chaplaincy Network (HCCN) first annual conference, Caring for the Human Spirit: Driving the Research Agenda for Spiritual Care in HealthCare. Research addressed spiritual care intervention with seriously ill patients, including those with advanced cancer and ALS. The studies focused on urban populations; caregivers; families of critically ill children; the benefits of a common language and set of activities; and the impact on medical outcomes at the end of life. All the research has implications for palliative care, hospice and advance care planning. “This is the first large-scale attempt at forming an evidence base for spiritual care effectiveness in health care,” said Rev. Eric J. Hall, HCCN President and CEO.

Pharma Velocity™ chosen by Rexall to support patient services across Canada JAeMarketing Management Inc. (JAeMM) announced today that Rexall has selected Pharma Velocity™as a platform for enhancing customer experience through an assortment of services and products. “Pharma Velocity™ represents JAeMM’s commitment to assisting retail and healthcare professionals in supporting Canadians to feel good about their health,” said James Oneschuk CEO, JAeMarketing Management Inc. “Pharma Velocity™ offers Canadian pharmacy a cost effective way to support more sophisticated programs and integrated services across millions of patients, including secure access to medication information online if they choose, and enables pharmacists to support patients and customers with more proprietary programs and services online, or through each store.” With a heritage dating back to 1904, Rexall and Rexall Pharma Plus pharmacies are among the most trusted names in retail pharmacy. Rexall is focused on helping Canadians feel good about their health through easy access to a wide assortment of health and wellness services and products.

Supported by a team of 8,600 employees in over 435 pharmacies across the country, Rexall is continually evolving to enhance the customer experience.

Atrium Innovations Announces Completion of Acquisition by the Permira Funds Atrium Innovations Inc. (“Atrium” or the “Corporation”), a globally recognized leader in the development, manufacturing and commercialization of innovative, science-based natural health products, announced today the successful completion of the previously announced plan of arrangement (the “Arrangement”) providing for the acquisition of all of the outstanding common shares of Atrium (“Atrium Shares”) by corporations backed by the Permira funds (“Permira”) and the acquisition by the Corporation of all of its outstanding 5.75% convertible unsecured subordinated debentures (“Atrium Debentures”).

Pursuant to the Arrangement, the former holders of Atrium Shares (other than the shares rolled over by Fonds de solidarité des travailleurs du Québec (F.T.Q.) (“Fonds”) and Caisse de dépôt et placement du Québec (“CDPQ”)) will receive, for each Atrium Share held, $24.00 in cash, and the former holders of Atrium Debentures will receive, for each $1,000 principal amount of Atrium Debentures, a cash amount of approximately $1,150 (representing the aggregate of $1,000 in principal amount, accrued and unpaid interest on such principal amount to, but excluding, February 13, 2014, and the interest that would otherwise be payable thereon from and including February 13, 2014 to, but excluding, March 15, 2014, as well as the applicable “make whole premium” on the basis of a stock price of $24.00). Permira has delivered to Computershare Investor Services, the depositary for the Arrangement, sufficient funds to enable the depositary to make the payments described in the Arrangement. In accordance with the Arrangement, payment will be made by the depositary to the holders of the Atrium Shares and Atrium Debentures as soon as practicable following the date hereof.

The Hydropothecary Corporation (THC) introduces luxury medical marijuana products The Hydropothecary President Sebastien St-Louis announced that prices will start at $18 per gram for their exclusive line up of medical marijuana products. “The Hydropothecary is developing the very best medical marijuana. Quality guides all our production decisions, never cost.” said St-Louis. With a brand new purpose built facility, state of the art phytotronic growing pods and uncompromising processes, The Hydropothecary is producing luxury medical marijuana for those with valid prescriptions. “Our process is significantly different from other industry players; strain specific lighting, strain specific food, 21 point room monitoring and control, and a signature ‘cold-snap’ cultivation process is just the start of it.

We’ve even implemented a glass-only policy so your marijuana is never stored in plastic.” said Co-founder and COO Adam Miron. Expected to sell out in record time, The Hydropothecary will exclusively cater to only 980 selected clients scheduled to begin August 2014.

22 www.ihpmagazine.com l April/May 2014

industry news Cardiome’s BRINAVESS Demonstrates 74% Cardioversion in Post-Cardiac Surgery Patients with Atrial Fibrillation Cardiome Pharma Corp. announced that a poster titled “Medical conversion with Vernakalant on postoperative cardiosurgical patients” by Thöne, M. et al., from the Department of Cardiovascular Surgery at the Heinrich-Heine-University Düsseldorf located in Düsseldorf, Germany, was presented at the 43rd Annual Meeting of the Germany Society for Thoracic and Cardiovascular Surgery held in Freiburg February 9-12, 2014. The study was an independent, investigatorled investigation that demonstrated real-world cardioversion experience with BRINAVESS™ (vernakalant IV) in patients who developed post-cardiac surgery atrial fibrillation (AF). This was a prospective, non-randomised, single-arm study in 50 patients with a variety of cardiac surgical procedures, ranging from coronary artery bypass graft (CABG) alone to complicated combination surgeries such as aortic valve (AV) and mitral valve (MV) replacement. The primary outcome was the conversion of atrial fibrillation to sinus rhythm (SR) at 90 minutes post-BRINAVESS infusion.

BRINAVESS was successful in cardioverting 74% of the patients. “We are extremely pleased with the real-world effectiveness that BRINAVESS demonstrated in cardioverting post-cardiac surgery patients,” said Dr. Steen Juul-Möller, Cardiome’s Medical Director. “This real-world experience of cardioverting 74% of AF patients is similar to what was demonstrated in Malmö, where 70% of non-cardiac surgery patients were effectively cardioverted with BRINAVESS. The high cardioversion efficacy coupled with its long term durability through patient discharge up to 8 days later makes BRINAVESS a valuable option for the management of post-cardiac surgery AF.”

National association of radiologists continues to support the use of mammograms regardless of recent report “Women should continue to seek breast cancer screening using mammography, a form of x-ray of the breast” emphasizes Dr. Jacques Lévesque, president of the Canadian Association of Radiologists (CAR), the national association representing radiologists in Canada. Results from the Canadian National Breast Screening Study (CNBSS) published in the British Medical Journal (BMJ) concluded that annual mammography does not reduce breast cancer deaths. CAR is very concerned that women will feel there is no need to pursue breast cancer screening, when in fact, several other breast cancer screening reports indicate the opposite. The CAR joins the American College of Radiology and the Society of Breast Imaging, who also have concerns that the report is “incredibly misleading analysis based on the deeply flawed and widely discredited Canadian National Breast Screening Study (CNBSS). The results of this BMJ study, and others resulting from the CNBSS trial, should not be used to create breast cancer screening policy as this would place a great many women at increased risk of dying unnecessarily from breast cancer.” The recently released CAR Practice Guidelines and Technical Standards for Breast Imaging and Intervention, as well as referral guidelines for medical imaging for physicians, encourages women to speak with their physician about the right time to begin mammography exams.

OncoGenex Announces Target Number of Events Reached in Phase 3 SYNERGY Trial of Custirsen in Metastatic Castrate-Resistant Prostate Cancer OncoGenex Pharmaceuticals, Inc. announced that the pre-specified number of events required for final analysis of the Phase 3 SYNERGY trial has been reached. The primary efficacy endpoint of SYNERGY will analyze overall survival benefit for custirsen in combination with standard first-line docetaxel chemotherapy and prednisone in men with metastatic castrate-resistant prostate cancer (mCRPC). Overall survival results will remain blinded until all study data have been thoroughly reviewed and prepared for final analysis. “The conclusion of SYNERGY represents a critical milestone for OncoGenex and the custirsen development program,” said Scott Cormack, President and CEO of OncoGenex. “Our teams are working diligently in order to announce survival results as soon as they are available, and we sincerely appreciate the support of the investigators, and most importantly, the men and their families who participated in this important trial.”

There have been 1,022 men enrolled into SYNERGY at 148 cancer centers throughout North America, Europe, Israel and South Korea. SYNERGY completed enrollment in 2012 and final survival results are expected to be announced by mid-2014. In the investigational arm of the trial, custirsen was administered as a weekly infusion of 640 mg following three loading doses, in combination with docetaxel and prednisone given as 3-week cycles. Patients in the comparator arm received docetaxel and prednisone without custirsen. In both arms, patients were treated until disease progression, unacceptable toxicity, or completion of up to 10 cycles, unless additional cycles were deemed beneficial by the treating physician. Custirsen received Fast Track designation from the FDA for the treatment of progressive metastatic prostate cancer in combination with docetaxel/prednisone. The FDA also agreed on the design of the SYNERGY trial via the Special Protocol Assessment process.

April/May 2014 l www.ihpmagazine.com 23

calendar APRIL April 24-26 2014 Canadian Respiratory Conference Organized by: Canadian Lung Association Calgary, AB For more information, visit lung.ca/crc/home-accueil_e.php April 24-27 16th Clinical applications for age management medicine conference Organized by: AMMG Orlando, Florida For more information, visit http://www.agemed.org April 25-27 Northwest Naturopathic Physicians Convention Organized by: BCNA British Columbia For more information, visit http://www.bcna.ca April 25-29 Canadian Conference on Medical Education Organized by: CCME Ottawa, ON For more information, visit mededconference.ca/ccme2014/ April 25-27 43rd Annual International Orthomolecular Medicine Today Conference Organized by: Canadian Society of Orthomolecular Medicine Vancouver, BC For more information, visit https://www. csom.ca/orthomolecular-medicine-today/

MAY May 2 A day of Derm for GPs Organized by: CFPC Toronto, ON For more information, visit http://www.cfpc.ca/upcomingevents May 3 Reducing and treatment of opioid dependency workshop Organized by: CFPC Toronto, ON For more information, visit http://www.cfpc.ca/upcomingevents May 8 Conquering Challenges in Osteoporosis management and treatment Organized by: CFPC Toronto, ON For more information, visit http://www.cfpc.ca/upcomingevents 24 www.ihpmagazine.com l April/May 2014

May 13 Using NSAIDs and COXIBs in patients with GI and CV Risk Organized by: CFPC Thunder Bay, ON For more information, visit http://www.cfpc.ca/upcomingevents May 14 Hormone testing methods available for both men and women Organized by: Restorative Medicine Online Teleconference For more information, visit http://restorativemedicine.org/cme-webinars/ May 23-25 First Line Therapy Certification Organized by: Metagenics Toronto, ON For more information, visit www.metagenics.com May 23-25 Natural health practitioners of Canada annual conference Organized by: NHP Canada Red Deer, AB For more information, visit http://www.nhpcanada.org

JUNE June 11 Treatment and prevention of adrenal hormone imbalances Organized by: Restorative Medicine Online Teleconference For more information, visit http:// restorativemedicine.org/cme-webinars/ June 19-21 Infectious Diseases for Primary Care Organized by: MCE Conferences Smokey Mountains National Park, Tennessee For more information, visit http:/www. mceconferences.com/medical-conferences. php June 21, 22 Nutrition for Docs: Part I Organized by: Canadian Society of Orthomolecular Medicine Ottawa, ON For more information, visit https://www. csom.ca/nutrition-for-docs/

JULY July 4-6 International Naturopathy Congress ICNM 2014 Organized by: ICNM Paris, France For more information, visit icnmnaturopathy.org

June 7 Integrative Medicine for Childrenâ&#x20AC;&#x2122;s Mental Health Organized by: Canadian Society of Orthomolecular Medicine Toronto, ON For more information, visit https:// www.csom.ca/integrative-medicine-forchildrens-mental-health/ July 9 Adaptogenic herbs and nutritional treatments for restoring optimal adrenal performance Organized by: Restorative Medicine Online Teleconference For more information, visit http:// restorativemedicine.org/cme-webinars/

AUGUST August 6-9 AANP Conference Organized by: AANP Keystone, Colorado For more information, visit http://www. naturopathic.org/aanp2014 August 13 Clinical applications of T4/T3 and the role of T3-containing compounds Organized by: Restorative Medicine Online Teleconference For more information, visit http:// restorativemedicine.org/cme-webinars/

SEPTEMBER September 10 Treatment of postmenopausal hot flashes and sleep disturbances Organized by: Restorative Medicine Online Teleconference For more information, visit http:// restorativemedicine.org/cme-webinars/

OCTOBER October 1 A closer look at estrogens, breast health, and other therapeutics Organized by: Restorative Medicine Online Teleconference For more information, visit http:// restorativemedicine.org/cme-webinars/ October 9-12 AARMâ&#x20AC;&#x2122;s Annual Conference Organized by: Restorative Medicine Online Teleconference For more information, visit http://restorativemedicine.org

NPN 80012473

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

Digestive Health and Colic Relief

What are BioGaia Probiotic Drops used for?

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

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

What is the Active Ingredient in BioGaia Probiotic Drops?

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

What is a probiotic?

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

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

What are BioGaia Probiotic Drops?

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

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

Are BioGaia Probiotic Drops safe?

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

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

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

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

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

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

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

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

Contraindications: Do not use if you are experiencing nausea, fever, bloody diarrhea or severe abdominal pain. Do not use if you have an immune compromised condition (e.g. AIDS, lymphoma, patients undergoing long-term corticosteroid treatment).

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

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

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

l . na tio Trad tri u N Di

ta Bo

S

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product profiles

I

W

Legend

l y lth re er tes try ics ics on lth lth ing tica icine icine ath ea ssu anc abe chia iatr riatr triti Hea Hea ell u p u C Di sy d e ns ace Med Med eo r H Pre u a r l Pe G ts N une en’s P d u n Co al Hom ut or m om sc loo et al/N Asia anic p a i B S V Im W D t . n Bo tio Trad tri Nu

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

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

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

• Provides 28g of high quality alpha+TM whey protein isolate per serving • Blends easily • Builds lean muscle* • Supplies a balance of all amino acids • Builds antibodies

ThyroLife® Optima ThyroLife® Optima is a unique and complete, wellbalanced multivitamin supplement for thyroid health.

It contains a complete mix of vitamins, antioxidants, micronutrients, amino acids and herbs to help support thyroid function, energy, mood and the immune system.

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

Mag-Matrix Liquid™

AOR CurcuVIVA

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

Sweetened with xylitol and a subtle but pleasing natural

CurcuVIVA contains Longvida® curcumin, the most bioavailable curcumin on the market with bioavailability increases of over 100-fold.

Just one capsule a day of CurcuVIVA provides curcumin’s powerful antioxidant and antiinflammatory activities, among many others benefits. Longvida® curcumin is exclusively available in Canada from AOR.

lemon flavour.

April/May 2014 l www.ihpmagazine.com 27

product profiles

Legend

l y lth re er tes try ics ics on lth lth ing tica icine icine ath ea ssu anc abe chia iatr riatr triti Hea Hea ell u p u C Di sy d e ns ace Med Med eo r H Pre u a r l Pe G ts N une en’s P d u n Co al Hom ut or m om sc loo et al/N Asia anic p a i B S V Im W D t . n Bo tio Trad tri Nu

New Healthy Transformation Weight Loss Program from Metagenics The FirstLine Therapy® Healthy Transformation Weight Loss Program is designed to make clinically supervised weight loss easier to implement and monitor to help achieve greater results and rewards. Modeled after a recent clinical study, it features a high protein, phytonutrientdense food plan with low-glycemic-load carbohydrates and a simple exercise plan. For easy dispensing, special program kits include a user-friendly patient guide and a 4-week supply of nutritional support for weight loss and overall health. Comprehensive program support materials include online resources for patients (recipes, FAQs, email support) and practitioners (implementation guide, group session presentations)—plus in-office brochures. For more information, call Metagenics at 800 268 6200.

PASCOE CANADA’s Whole Body Cleanse® Whole Body Cleanse® is an easy-to-use homeopathic detoxification protocol.

All the major systems involved in detoxification are supported by this unique formulation: JUNIPERUS Similiaplex®: kidneys; QUASSIA Similiaplex®: liver; LYMPHDIARAL®: lymphatic system. For more information, visit: www.pascoecanada.com.

BASENTABS pH-balance PASCOE® The Basis of Health Are your patients suffering from persistent stress, chronic fatigue or nutritional imbalance? If they are experiencing any of these, they might need support to regulate their acid-base balance. For all important metabolic functions to work optimally, the body’s acid-base balance must be in equilibrium. BASENTABS pH-balance PASCOE® is a revolutionary formula with a balanced mixture of bicarbonates, now with Zinc.

Proven high alkalinizing capacity, a key basic therapy for chronic illnesses, free of sugar, gluten and lactose For more information, visit: www.pascoe.ca.

GENESTRA BRANDS Active Multi Vite Without A is a vitamin mineral supplement shown to advance overall growth and development as well as helps maintain proper muscle, immune function and healthy skin.1 The synergistic preparation contains bioavailable forms of folate (L-methylfolate), vitamin B6 (pyridoxal-5phosphate), and calcium (calcium citrate). The convenient tablet formula is dairy-free, gluten-free and is suitable for vegetarians.

28 www.ihpmagazine.com l April/May 2014

product profiles

Legend

l y lth re er tes try ics ics on lth lth ing tica icine icine ath ea ssu anc abe chia iatr riatr triti Hea Hea ell u p u C Di sy d e ns ace Med Med eo r H Pre u a r l Pe G ts N une en’s P d u n Co al Hom ut or m om sc loo et al/N Asia anic p a i B S V Im W D t . n Bo tio Trad tri Nu

EGCG SAP Science-based ultra-antioxidant from green tea Epigallocatechin gallate (EGCG) is a powerful natural antioxidant, and the major chemoprotective agent in green tea. Combined with anthocyanidins and lycopene, this standardized synergistic blend of antioxidants is supported by a wealth of scientific literature. A potent and popular choice of healthcare practitioners for combating oxidative stress; EGCG is designed to address the underlying process behind a myriad of chronic and degenerative conditions, including cancer and cardiovascular disease.

BCAA+creatine • Increases lean muscle mass • Improves strength, power, and performance • Helps support the immune system • Gluten Free & 100% vegan • Lemon-Lime flavour…Tastes great!

BioGaia BioGaia® is a probiotic that helps promote a healthy, balanced digestive system. It has demonstrated beneficial effects on digestive upsets such as diarrhea, constipation, gas and bloating.

Grape Seed SAP GENESTRA BRANDS HMF Intensive Powder Intensive Powder is a probiotic supplement that can be used daily on a long-term maintenance regime. Providing 25 billion CFU per dose, the easy-to-use powder formula quickly dissolves in liquid and can be added to water or milk.

HMF Intensive Powder helps reduce symptoms associated with intestinal discomfort1, helps restore intestinal flora post antibiotic therapy2, and is highly recommended after completion of the HMF Replete program.

Science-based antioxidant and anti-inflammatory The proanthocyanidins from grape seed extract (GSE) demonstrate anti-inflammatory mechanisms and exhibit cytotoxic behaviour towards human breast, lung and gastric adenocarcinoma cells. With superior freeradical scavenging ability to Vitamins C, E, and beta-carotene, GSE is a powerful antioxidant, which may protect organs and tissues from the toxic effects of pharmaceutical drugs and environmental stressors, while preventing the development of atherosclerotic plaques.

April/May 2014 l www.ihpmagazine.com 29

TRUST. IN NUTRITIONAL HEALTH.

Small Pure Potent

SUPERCRITICAL CO2 TRIGLYCERIDE CritiCal ExtraCtion • CritiCal Purity CritiCal BioavailaBility • CritiCal ConCEntration “There’s growing evidence that the natural triglyceride form or reesterfied form of the omega 3 fatty acids has the greatest absorption.

It also significantly increases the Omega-3 index.”

Dr. Martin P. Gallagher

866.856.9954 • douglaslabs.ca

QüELL FISH OIL SupErcrItIcaL cO2 trIgLycErIdE

QÜELL Fish Oil is Supercritical CO2 extracted oils in triglyceride form, manufactured in Germany exclusively for Douglas Laboratories. QÜELL Fish Oil is unique among other fish oils for its’ critical extraction, purity, bioavailability and concentrations.

Critical Extraction Supercritical CO2 advanced technology is the superior protection against oxidation. The extraction method of fish oil uses less heat and no chemical solvents when compared to molecular distillation, resulting in fewer unwanted isomer formations and “cleaner” oil.

Critical Purity Supercritical fluid extraction uses CO2 (carbon dioxide) instead of oxygen to gently extract the fatty acids, which also protects them from microorganisms that can’t survive without oxygen.

No chemical preservatives, solvents, or undesirable compounds are found in QÜELL Fish Oils. Heavy metal and contaminant levels measure significantly lower than the standard.

Critical Bioavailability Recent scientific data shows the triglyceride form of fish oil is better absorbed when compared to ethyl esters. Recent data have demonstrated that omega-3 fatty acids delivered in a triglyceride form may result in greater plasma levels and a higher omega-3 index compared with omega-3 fatty acids delivered in the form of ethyl esters.

QÜELL Oil

>75% Omega-3

High dHa 2 softgels Omega-3 Supercritical CO2 Triglyceride Concentrate

1,250 mg

Providing:

Typical Fish Oil vs.

Omega-3 supplementation The benefits of omega-3 fatty acids continue to emerge and numerous health organizations around the world recommend increasing the daily intake of EPA and DHA. Data continues to accumulate that supports EPA and DHA in cardiovascular health as well as many other areas, including neurological health, vision health, and joint health. The omega-3 fatty acid EPA is the direct precursor for the prostaglandins, which are involved in helping to maintain the body’s normal inflammatory processes. DHA plays a major role in the structural integrity of neuronal membranes. DHA is essential for neurological and visual development and is vital throughout pregnancy to support fetal brain growth and formation of the retina and visual cortex. As the most abundant fatty acid in the brain, adequate amounts of DHA are needed throughout infancy and adulthood for ongoing optimal function. Low levels of DHA may adversely influence behavior and mental performance, and have been correlated with changes in disposition, memory, visual and other neurological parameters.

70% “Other”

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DHA

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EPA

200 mg

High Epa 2 softgels

Critical Concentration Many fish oils contain only about 30% omega-3 fatty acids, of which roughly 18% is EPA and 12% DHA. The remaining 70% is a varying mixture of other components. In other words, regular fish oil contains less than a third of the desired active ingredients and more than two thirds of “other” components.

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

Environmental Impact QÜELL uses wild fish such as anchovies, sardines and mackerel that are recognized as not being endangered species. The production process produces no toxic impurities or solvents and all waste and waste water are recycled or transformed into energy.

No fishy smell The QÜELL fish oils are naturally free of odor and taste due to the supercritical CO2 purification process, which allows for a pleasant experience when consuming fish oil.

Omega-3 Supercritical CO2 Triglyceride Concentrate

1,250 mg

Providing: EPA

800 mg

DHA

150 mg

High Epa +dHa with Vitamin d3 1 softgel Vitamin D3

1,000 IU

Omega-3 Supercritical CO2 Triglyceride Concentrate

1,250 mg

Providing EPA

600 mg

DHA

400 mg

For more information, please visit douglaslabs.ca.

866.856.9954 douglaslabs.ca

32 www.ihpmagazine.com l April/May 2014

cover story

Clinic One

by Philip Rouchotas, Msc, ND photographs by Hart Macklin

Clinic One is an innovative health care center located in the heart of Winnipeg’s exchange district. The philosophy of the center is based on utilizing the combined expertise of various health professionals who are members of its interdisciplinary team. The clinic, founded by Dr. Meer Janjua MD, CCFP, boasts of a medical doctor working alongside a naturopathic doctor and a pharmacist. The clinic’s motto is “One team, one life,” describing the concept of several interdisciplinary practitioners coming together serving the same purpose: offering their patients the most complete and highest quality integrative medical care.

Dr Meer Janjua, MD, CCFP Clinic One is located on the main floor of a unique, historical building, the Maltese Cross Building. This seven-story heritage building was erected in 1909 for the Winnipeg Rubber Company, and served as one of the first distribution centers for goods traveling into Western Canada. The Company’s trademark was the modified Maltese Cross, which traces its roots to the Knights of St. John of Jerusalem during the time of the Crusades. This symbol can be found adorning the stone trim of the building. Today the building has been adapted as office space in the heart of Winnipeg.

Dr. Meer Janjua MD, CCFP, is the clinic’s founder and a second-generation physician, whose father has practiced in the Toronto area for most of his life. Dr. Janjua completed his own studies in a number of countries, including premed at Hawaii Pacific University, kinesiology and health sciences at York University, and his medical degree at the University of the West Indies in Trinidad. Dr. Janjua has both Canadian and British citizenship and his medical degree is internationally recognized. He completed his residency in family medicine in 2011 at the University of Manitoba, where he fell in love with Winnipeg and decided to stay.

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cover story

Dr. Janjua attributes his open mindedness in part to his travels. International travel allowed him to become better acquainted with “people different than myself,” and in addition to broadening his understanding of humanity in general, he says that this experience has made him a better physician and health care provider. It has taught him to respect customs, which in turn enhances patient compliance.

Being of Indian descent and the fact that he speaks Hindi also helps him better reach out to and serve the immigrant community in Winnipeg.

Dr. Janjua’s practice focuses on primary care. He treats a range of commonly occurring conditions in the community, for instance hypertension, diabetes, and thyroid disorders, however he also has a developed interest in surgery. He has a surgical rotation at the nearby Grace Hospital, where he assists in surgeries, and also performs out-patient minor surgery at the clinic. When his patients ask for nonpharmaceutical strategies to help manage their conditions, he openly refers them to Dr. Kelly Brown, the naturopathic doctor within the clinic. In these situations, Dr. Janjua will then collaborate with Dr. Brown afterwards to monitor the patient’s ongoing status.

Dr. Janjua is noticeably enthused about having an interdisciplinary team at the clinic. He actively sought to bring a naturopathic doctor to the clinic. He sees conventional medicine as being deeply rooted in naturopathic medicine historically, and is convinced that “every modality has its place in healthcare.”

He has been impressed with how NDs treat the patient as a whole, and sees naturopathic medicine as an important part of disease prevention. Of the allconventional versus all-natural stances, he states that “neither extreme works well.”

Instead, to truly help people, he says that the collaborative approach is key.

Dr. Kelly Brown, ND is a 2010 graduate from the Canadian College

of Naturopathic Medicine. She offers natural therapies for a range of commonly presenting conditions including women’s health issues, endocrine disorders such as hypothyroidism and diabetes, digestive disorders, skin conditions, immune problems, as well as mental health issues from stress and anxiety to addiction. Dr. Brown also offers acupuncture services for various conditions, as well as objective testing in the form of bloodwork, food allergy testing, and hormone analysis.

We have had the privilege of interviewing many integrative MDs; Dr. Janjua conversely practices a very conventional form of medicine, while fully appreciating the value of natural medicine, and active collaboration with an ND. He fully utilizes the diagnostic and therapeutic tools in which he has been trained, yet encourages his patients to obtain specialized ND care where appropriate, to benefit from complementary testing, nutritional counseling, supplementation, and other natural healing strategies. We feel that this type of complementary relationship where there is room for both conventional medicine and naturopathic medicine practiced at their best, with the element of collaborative patient management - is the future of integrative medicine.

In addition to Dr. Brown ND, the clinic also has an internist that does consults on a part time basis. He treats patients with advanced, uncontrolled diabetes, performs cardiac stress tests, and conducts cardiac assessments. The clinic has also very recently added a chiropractor, and a registered massage therapist to the team, and plans to add psychological services and conduct Restricted Environmental Stimulation Therapy and Floatation Research in the fall. This innovative and dynamic clinic is also reaching out to its patients using social media, including profiles on facebook and twitter. As part of this more holistic, convenient, and interactive style of medicine, the clinic accepts walk-in patients and patients without a referral.

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Dr. Janjua has a love of historical buildings, and he sees the physical environment as a critical element of a patient’s therapeutic experience. In the clinic’s historical surroundings, high ceilings, and natural lighting, he watches patients’ stress levels immediately fall, and their sense of wellbeing begin to improve. The clinic’s décor is a combination of rustic and modern. The ceilings in the reception area are 4.6 meters high, with heating ducts and other mechanical systems fully exposed. Large windows run the length of the wall, filling the room with natural light. Each of the nine clinic rooms is fitted with a different, refurbished antique door. Dr. Janjua is also an avid student of history, and over time he has accumulated a collection of historical medical artifacts.

He is in the process of preparing a display for them within the clinic.

local media outlets. We think the clinic’s distinct appearance fits well with and draws attention to the clinic’s unique, progressive vision of healthcare. In this distinctive clinic, the collaborative relationship between practitioners and the clean, uplifting environment work together to create both an inspiring and a therapeutic milieu.

Dr. Janjua says the feedback from patients has been outstanding. Patients love it because it is so different from any other clinic, and makes their visit an enjoyable experience rather than a chore. The clinic has received considerable attention in the community and has been featured by

IHP thanks Dr. Janjua and the Clinic One team for allowing our readers a brief look into the inner workings of their unique team and facility. We wish the clinic much success in bringing truly progressive, integrative medicine to the city of Winnipeg.

Clinic One boasts an affiliated pharmacy managed by pharmacist Jeff Froese. The Clinic One Pharmacy focuses on meeting the individual needs of patients, offering patient consultations, personalized home visits, diabetes support, compounding services and blister pack drug preparation, as well as free prescription delivery. The pharmacy also carries a selection of professional line natural health products to complement the emphasis on natural healing at the clinic.

April/May 2014 l www.ihpmagazine.com 37

TM

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

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PRODUCT mOnOgRaPh

PRODUCT MONOGRAPH OIL OF OREGANO

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

Human studies

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

Animal and In vitro studies

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

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

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

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

Toxicology

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

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

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

References

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

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

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

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

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

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

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

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

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

2006;69(2):369-75.

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

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clinic profile

Living Well Integrative Health Center Collaboration On The East Coast

By Christopher Habib, ND

Living Well Integrative Health Center 2176 Windsor Street, Halifax, NS Phone: (902)-406-1500 Website: http://www.livingwellihc.ca

40 www.ihpmagazine.com l April/May 2014

Doctors Theresa Jahn, ND and Rochelle Wilcox, ND were classmates and graduated from the Canadian College of Naturopathic Medicine in 2010. Returning to their roots, they relocated to the East Coast upon graduation, initially practicing in two different clinics within the city of Halifax.

Both having an interest in creating more awareness and continuing education opportunities in Atlantic Canada, in 2011 and 2012 they co-chaired the Nova Scotia Naturopathic Conference. Working together, they were able to further develop the conference to attract a growing number of NDs from Atlantic Canada as well as Ontario, making this appealing for increased company sponsorship.

This has helped to foster greater awareness, collaboration and communication within the Atlantic provinces for Naturopathic Doctors. During this time, Dr. Jahn and Dr. Wilcox developed a great working relationship and were exploring opportunities to be able to practice together.The Living Well Integrative Health Centre opened in September

clinic profile

2012 as a brand new initiative founded by Dr. Maria Patriquin MD, CCFP. The Centre is a two-story house that has been converted into commercial real estate.

With a bright, peaceful and welcoming feel, the centre has hardwood floors, along with original artwork decorating it’s walls. It has 7 treatment rooms, one of which is large enough to host small group workshops and currently Dr. Patriquin MD is facilitating a Mindfulness Based Stress Reduction group.

The opportunity to join this centre coincided with Drs. Jahn and Wilcox’s desire to work together within an exciting and collaborative environment.

Alongside Drs. Jahn, Wilcox and Patriquin, the Centre also hosts a Registered Clinical Psychologist, a Clinical Social Worker, and a Physiotherapist.

To the best of our knowledge, this is currently the only centre in Atlantic Canada that includes both Naturopathic and Medical Doctors. The practitioners

at Living Well all maintain their own independent practices, while having an enhanced opportunity for collaboration and interdisciplinary learning.

Drs. Jahn and Wilcox make an effort to meet other practitioners within the community to create better working relationships and really feel further improvements in this domain would create a more optimal experience for patients and practitioners alike. When asked if they have any messages for other practitioners, they reply: “In our experience, reaching out to other practitioners to collaborate with them and to encourage patients to communicate with their healthcare providers has increased efficiency and improved care.”

Doctors Jahn and Wilcox have different clinical interests. Dr. Jahn’s primarily focuses on women’s health, weight loss, athletes, and mental health.

April/May 2014 l www.ihpmagazine.com 41

clinic profile

While Dr. Wilcox has an interest in chronic disease management. Addressing stress reduction is a large component of both their practices, and they have facilitated many workshops on this topic.

Drs. Jahn and Wilcox have their own dispensary, carrying products by reputable companies such as Ascenta, NFH, Thorne, Cytomatrix, Heel, Mediherb, Douglas Labs, Metagenics, Vibrant Health, and Genestra.

They also carry tinctures and ointments by St. Francis Herb Farm. They use labs such as: Rocky Mountain Analytical, Labrix, and Genova and bioimpedance analysis for the appropriate patient populations.

A challenge of being an independent practitioner within a collaborative setting, has been determining an appropriate marketing strategy. They market themselves individually as well as collectively. The

42 www.ihpmagazine.com l April/May 2014

Centre maintains a website, and each practitioner also has their own. They have found, when working as a team, it is essential to assess the type of marketing vehicle, the target audience and how best to convey integrative healthcare. They have participated in Womenâ&#x20AC;&#x2122;s Health Expos, have been featured in local newspapers, use print advertising and continue to give talks within the community. Drs Jahn and Wilcox are currently partnering with the Psychologist Harpreet Aulakh at Living Well, offering presentations to bring awareness to collaborative care at schools within the surrounding area.

Drs. Jahn and Wilcox feel there is an increasing public awareness and interest in the Naturopathic profession, noting significant growth within the membership of the Nova Scotia Association of Naturopathic

clinic profile

Doctors within the last few years. Both doctors find this exciting as this will help to create further awareness and increased opportunities for Naturopathic Doctors on the East Coast.

In terms of future directions, Dr. Wilcox is currently pursuing continuing education in Biological Medicine and envisions that it will have a greater role within her practice. As Dr. Jahnâ&#x20AC;&#x2122;s uses a Functional Medicine approach in her practice and her continuing education focuses on this she would like to offer lifestyle based wellness programs in the future. We wish these wonderful practitioners continued success.

--------------------------------------------------------------------Maria Patriquin MD, CCFP Clinic Owner Harpreet Aulakh Reg. Psych Jennifer van Kessel MSW, RSW Theresa Jahn BSc ND Rochelle Wilcox BA ND Robin Stamm MPT Jane White, Administrative Staff Susan MacLean, Administrative Staff

April/May 2014 l www.ihpmagazine.com 43

The Journal Of

Integrated Healthcare

Practitioners 1

p51

The Case for Blood Donation Why Blood Donation is a Larger Health Issue than Generally Appreciated

By William R. Ware, PhD

2

p58

The HypothalamusPituitary-Adrenal Axis

Role in Borderline Personality Disorder

By Tanya Lee, ND

3

p65

NEM

Novel Joint Care Supplement

By Christopher Habib, ND

CE

p73

Acetyl-L-carnitine for depression and mood disorders A novel therapeutic approach

By Rochelle Fernandes, MSc., ND (Cand)

44 www.ihpmagazine.com l April/May 2014

editor’s letter

April Showers April has to be the only month of the year when the site of rain brings pure joy.

Partially because it signifies the end of winter, partially because it washes away the last of the snow and reveals our garden! Unfortunately, it comes with a clear reminder of the work ahead to get the abandoned patch of dirt into shape.

An MD who chooses to pursue a path in integrative medicine is an immensely valuable ally in bridging the gap between conventional and integrative practice, and at IHP we have had the privilege of showcasing many such pioneering individuals. Yet we have always felt that the next step in building the bridge looks quite different; how about a purely conventionally minded/ practicing physician who feels there is value to be offered by integrative providers, and welcomes them into his/ her facility? An MD who informs patients of several treatment options, allows the patient to make an informed decision, and if “natural” is chosen, continues to deliver world class conventional strategies of monitoring and case management? We are excited to feature Dr Meer Janjua, MD and the Clinic One- Winnipeg team as the issue’s cover story.

Our clinic profile features Theresa Jahn, ND, and Rochelle Wilcox, ND, of the Living Well Integrative Health Centre in Nova Scotia. The two have made tremendous strides in improving the political landscape of naturopathic practice in eastern Canada, and exemplify their goals in practice through partnering in a truly collaborative and integrative environment with multiple allied healthcare providers.

The issue features a second contribution from frequent contributor William R Ware, PhD, regarding potential deleterious health consequences from iron stores within normal limits. Tanya Lee, ND, provides a compelling look at HPA axis function in borderline personality disorder, and Chris Habib, ND, provides a critical evaluation of the available evidence for a new anti-inflammatory molecule generating tremendous interest; NEM. The issue’s continuing education article is an excellent review of L- Carnitine for management of depression by Rochelle Fernandes, MSc, ND (Cand).

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

April/May 2014 l www.ihpmagazine.com 45

Integrated Healthcare

Practitioners Publisher | Sanjiv Jagota (416) 203-7900 ext 6125 Editor-in-Chief | Philip Rouchotas, MSc, ND (416) 203-7900 ext. 6109 Associate Editor | Christopher Habib, ND Production Manager | Erin Booth (416) 203-7900 ext. 6110 Junior Designer | Tamara Kelly Contributors Philip Rouchotas, MSc, ND Christopher Habib, ND Tanya Lee, ND William R Ware, PhD Rochelle Fernandes, MSc, ND (Cand) President | Olivier Felicio (416) 203-7900 ext. 6107 Controller & Operations | Melanie Seth Advertising Information Sanjiv Jagota | Tel: (416) 203-7900 ext 6125 Email: sanjiv@ihpmagazine.com Jeff Yamaguchi | Tel: (416) 203-7900 ext 6122 Email: jeff@gorgmgo.com 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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Published by IHP Magazine

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

46 www.ihpmagazine.com l September 2013

peer review

Peer Review Board Members Andrea Maxim, ND Healing Journey Naturopathic Clinic 25 Caithness St. W. Caledonia, Ontario N3W 1B7 andreamaximnd@gmail.com Anthony Moscar, ND Mahaya Forest Hill 73 Warren Road, Suite 102 Toronto, Ontario M4V 2R9 anthonymoscar@gmail.com Aoife Earls, MSc, ND Trafalgar Ridge Chiropractic and Acupuncture 2387 Trafalgar Road, Unit 7A Oakville, Ontario L6H 6K7 aearlsnd@gmail.com Ashley Weber, HBSc, ND Upper Beach Health and Wellness 1937 Gerrard St E. Toronto, Ontario ashleywebernd@gmail.com Berchman Wong, ND Adjust Your Health 5809 Macleod Tr SW, Suite 218 Calgary, Alberta T2H 0J9 berchman.nd@gmail.com Betty Rozendaal, BES, MA, ND Thornhill Naturopathic Health Clinic 12A Centre Street Thornhill, Ontario L4J 1E9 drbetty@thornhillnaturopathic.ca Brock McGregor, ND McGregor Naturopathic 220 St Clair Street Chatham, Ontario N7L 3J7 drbrock@mcgregornd.com Carol Morley, ND Zawada Health 201 City Centre Drive, Suite 404 Mississauga, Ontario L5B 2G6 info@zawadahealth.com Christopher Knee, ND, MSc The Dempster Clinic â&#x20AC;&#x201C; Center for Integrated Medicine 97 Scollard Street

Toronto, Ontario knee.christopher@gmail.com

Hammonds Plains, Nova Scotia B4B 1B4 erinbalodis@gmail.com

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

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

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

Faryal Luhar, ND Healthwise Wellness 4250 Weston Rd Toronto, Ontario M9L1W9 ndluhar@hotmail.com

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

Heidi Fritz, MA, ND Canadian College of Naturopathic Medicine 1255 Sheppard Ave East Toronto, Ontario M2K 1E2 hfritz@ccnm.edu

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

Isaac Eliaz, MD, MS, LAc Amitabha Medical Clinic & Healing Center 7064 Corline Ct #A Sebastopol, California 95472-4528 ieliaz@sonic.net Jacob Scheer, DC, ND, MHSc 2100 Finch Ave. W. #206 North York, Ontario M3N 2Z9 Jacob.Scheer@utoronto.ca Jiselle Griffith, BSc, ND The Health Hub Integrated Clinic 12 Irwin Ave, Suite 200 Toronto, Ontario jiselle@healthhubclinic.com John David Millar, BSc, ND Jacksoncreek Natural Health Centre 187 Sherbrooke St. Peterborough, Ontario naturo@jacksoncreek.ca Jordan Robertson, BSc, ND Lakeshore Clinic 2159 Lakeshore Road Burlington, Ontario L7R 1A5 jordanrobertsonnd@gmail.com

April/May 2014 l www.ihpmagazine.com 47

peer review Judah Bunin, BSc, MSc, ND, DrAc Fredericton Naturopathic Clinic 10-150 Cliffe St Fredericton, New Brunswick E3A0A1 frednatclin@yahoo.ca Karam Bains, BSc, ND Inside Out Wellness 3650 Langstaff Road, Unit 12 Woodbridge, Ontario karam@elixirhealth.ca Kate Whimster, ND Kew Beach Naturopathic Clinic 2010 Queen Street East, 2nd floor Toronto, Ontario kwhimster@wavelengthwellness.com Kendra Smith, ND Toronto, Ontario drkendra.nd@gmail.com Kelly Brown, BSc, ND Clinic One 286 McDermont Avenue Winnipeg, Manitoba R3B 1H6 drkbrownnd@gmail.com Leigh Arseneau, ND Centre for Advanced Medicine 670 Taunton Rd East Whitby, Ontario L1R 0K6 info@advancedmedicine.ca Lindsay Bast, BSc, ND Greenwood Wellness Clinic PO Box 189 1400 Greenwood Hill Rd. Wellesley, Ontario N0B 2T0 lindsay.bast@greenwoodclinic.ca Louise Wilson, BSc, ND 320 Queen St S Bolton, Ontario L7E 4Z9 dr.louisewilsonnd@gmail.com Maria Shapoval, ND Canadian College of Naturopathic Medicine 1255 Sheppard Ave East Toronto, Ontario M2K 1E2 mshapoval@ccnm.edu Makoto Trotter, ND Zen-tai Wellness Centre 120 Carlton Street, Suite 302 Toronto, Ontario M5A 4K2 makoto@zen-tai.com

48 www.ihpmagazine.com l April/May 2014

Mandana Edalati, BA, ND Wellness Naturopathic Centre Suite 213-1940 Lonsdale Ave North Vancouver, British Columbia V7M 2K2 dredalati@gmail.com Meghan MacKinnon, ND Armata Health Centre 126 Welling St. W, Unit 201B Aurora, Ontario L4G 2N9 drmeg.nd@gmail.com Melanie DesChatelets, BSc, ND True Health Studio 200-4255 Arbutus St Vancouver, British Columbia V6J 4R1 melanie@drdeschat.com Misa Kawasaki, BSc, ND Meridian Wellness 13085 Yonge Street, Suite 205 Richmond Hill, Ontario L4E 3S8 drkawasaki@meridianwellness.ca Nicole Egenberger, BSc, ND Remede Naturopathics 214 Sullivan Street Suite 3B New York, New York 10012 info@remedenaturopathics.com

Sarah Vadeboncoeur, ND Ottawa Integrative Health Centre 1129 Carling Ave Ottawa, Ontario K1Y 4G6 sarahmvadeboncoeur@gmail.com Scott Clack, ND Touchstone Naturopathic Centre 950 Southdown Rd, Unit B5 Mississauga, Ontario L5J 2Y4 sclack.nd@touchstonecentre.com Shawna Clark, ND Forces of Nature Naturopathic Clinic 2447 1/2 Yonge St Toronto, Ontario M4P 2E7 info@shawnaclarknd.com Stephanie Swinkles, DDS Elmsdale Dental Clinic 4-269 Highway 214 Elmsdale, Nova Scotia N2S 1K1 steph_moroze@hotmail.com Susan Coulter, BSc, ND Roots of Health 2-497 Laurier Ave Milton, Ontario L9T 3K8 scoulter@rootsofhealth.ca

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

Sylvi Martin, BScN, ND Fusion Chiropractic and Integrative Health 735 Danforth Avenue Toronto, Ontario M4J 1L2 sylvi.martin@gmail.com

Rajesh Ragbir, ND Scarborough Naturopathic Clinic 1585 Markham Road, Suite 211 Scarborough, Ontario M1B 2W1 ragbir.nd@gmail.com

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

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

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

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

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

editorial board

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, professionleading ND’s, and members of academia. This unique blend of minds comes together and has already provided insight that is actively

shaping the manner in which IHP is compiled.

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

Jason Boxtart, ND

Dr Boxtart is currently serving as Chair to the Board of Directors for the Canadian Association of Naturopathic Doctors, the national association of naturopathic medicine in Canada.

In that position he also chairs the Canadian Naturopathic Coordinating Council, the national stakeholder group in Canada. He also is a Board member of the Canadian Naturopathic Foundation, the national naturopathic charity. For the last eight years Dr Boxtart has held a Faculty of Medicine post with the University of Northern British Columbia. Jason, and his wife Dr Cher Boomhower, ND, share the role of Medical Director for the Northern Center for Integrative Medicine, a multipractitioner 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.

April/May 2014 l www.ihpmagazine.com 49

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 was the first Canadian Naturopathic Physician to qualify with a fellowship from the American Board of Naturopathic Oncology in 2007. He and his wife, Dr. Karen Parmar launched the Integrated Health Clinic in 2000 and have since facilitated its growth to become one of the largest integrated health care facilities in Canada. Dr. Parmar was a consulting naturopathic physician at the Lions Gate Hospital cancer clinic from 2008 to 2012. He has established collaborative relationships with many oncologists and other practitioners, ensuring patients are provided a truly integrative and evidence-guided treatment. Dr. Parmar is also active in writing and lecturing in the fields of clinical hyperthermia, the tumour microenvironment, and integrative oncology. He continues to serve as a board member for the Oncology Association of Naturopathic Physicians, a position he has held since 2008. He is licensed by the College of Naturopathic Physicians of B.C.

Kristy Prouse, MD, FRCSC

Dr Prouse has practiced as an Obstetrician/Gynaecologist for over 10 years and currently holds the position of assistant professor at the University of Toronto and the Northern Ontario School of Medicine. Dr Prouse completed her medical degree at Queen’s University and residency training at the University of Calgary. Additionally, Dr Prouse has trained in bio-identical hormone replacement therapy and anti-aging and regenerative medicine through the University of Southern FloridaCollege 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 metaanalyses. Ongoing projects include three multi-centred randomized clinical trials and a comprehensive CIHR synthesis review of natural health products used for cancer. Dugald is currently a member of Health Canada’s Expert Advisory Committee for the Vigilance of Health Products and is a peer reviewer for the Canadian Adverse Reaction Newsletter.

50 www.ihpmagazine.com l April/May 2014

The Journal of IHP

1

The Case for Blood Donation Why Blood Donation is a Larger Health Issue than Generally Appreciated By William R. Ware, PhD

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

Abstract Blood donation is probably more often motivated by altruism than by the notion that it carries health benefits. Iron is involved in many biological processes. It is also well known to be a source of reactive oxygen species (ROS) trough the Fenton reaction, and the result can be oxidative stress with cellular, DNA, vascular and organ damage. The currently used laboratory reference range for normal serum ferritin typically covers from the 5th to the 80th or 90th population percentile and is gender dependent. However, there is considerable evidence that within this range adverse effects of iron are implicated, which impact the development and progression of a number of common disorders. There is also considerable data indicating that lowering ferritin levels within the normal range to values corresponding to near iron depletion produces beneficial results for a number of diseases.

In addition, oxidative DNA damage is strongly and significantly correlated with ferritin levels within the normal reference range with no apparent threshold. There appears to be no consensus as to what constitutes an optimum level of iron body stores. However, there is a large range of these stores between anemia and abnormal levels that suggest intervention. It is suggested that optimum ferritin levels may be at the low end of the normal reference range near the threshold for anemia. The simplest and quickest way to dramatically lower ferritin levels is blood donation.

April/May 2014 l www.ihpmagazine.com 51

Introduction In the September 2013 issue of Integrated Healthcare Practitioners, the potential toxicity of iron and the connection between iron and diabetes was explored (Ware 2013). While not emphasized, elevated levels of serum ferritin, a measure of iron body stores and active iron, are associated with enhanced risk for a number of disorders, and the levels from which lowering produced clinical benefits were well below the upper limit of the normal reference ranges used internationally. In what follows, this observation will be generalized to a number of disorders and the question, “what is the optimum serum ferritin level?” will be addressed.

Hemochromatosis is not generally treated until ferritin levels are considerably above these upper limits of normal (Adams 2011).

The multiplicity of physiologic processes involving ferritin, and in particular its role as an acute phase reactant, has caused some to question the use of serum ferritin as a marker for the risk of various disorders (Adams 2012, Lee 2004). However, as will be discussed, risk of incidence of various disorders correlates with ferritin levels in a large number of studies with large sample size and a diversity of disorders. More importantly, there are also a number of disorders where lowering “normal” ferritin by blood removal and driving ferritin levels from above, near or even below the population mean to near iron depletion (threshold for anemia) produces significant improvements in clinical manifestations or markers.

Thresholds of ferritin levels and risk of disease

Ferritin reference ranges and levels regarded as normal There is some variation in the upper reference limits for serum ferritin that constitute a threshold for concern. In North America, typical values for the upper limit of normal are 300-320 ng/mL for men, and 150-307ng/ mL for women. Similar values are common in other regions. In a recent discussion of the diagnosis of hyperferritinemia, the authors indicate elevated ferritin levels are >300 ng/ mL for men and >200 ng/mL for women.

52 www.ihpmagazine.com l April/May 2014

In addition to the associations between ferritin levels and diabetes discussed in the cited IHP article, the following are of interest.

• In a study of men and postmenopausal women, a ferritin threshold of >200 ng/mL was associated with an increase in risk of a first heart attack (Holay 2012).

• A study classified CHD-positive patients as having one or more coronary arteries with ≥ 50% blockage. Comparison of ferritin levels revealed that those CHD-positive had on average ferritin levels of 121 vs. 73 ng/mL for those CHD-negative (Haidari 2001).

• At a ferritin threshold of >137 ng/mL, increased risk of ischemic stroke was found in a study of postmenopausal women (van der A 2005).

Photo©iStockphoto.com

The variation of serum ferritin levels with age and gender in the US can be obtained from the Third National Health and Nutrition Examination Survey (NHANES III) (Zacharski 2000). For Caucasian men, the mean serum ferritin at age 17-19 is about 60 ng/mL and by age 30-39 has a plateau at about 150 ng/mL where it remains until about age 60 when a steady decline to about 90 ng/mL by age 90 is observed. For women, the mean value is quite constant at around 30 ng/mL until after menopause and then increases to about 80 ng/mL by age 60 and then gradually increases to about 100 ng/mL at age 80-90.

The Journal of IHP • A ferritin threshold of 145 to 164 ng/mL was found for increased risk of acute ischemic stroke transforming to a hemorrhagic stroke in older men and women (Choi 2012).

• A large study examined the association between ferritin levels and laboratory measured cardiovascular fitness (CVF) in young men. The likelihood of the absence of CVF, adjusted for numerous potential confounders, became significantly apparent at a ferritin threshold of >150 (Mainous 2009).

• Middle-aged men had significant risk of developing hypertension, defined as BP ≥ 140/90 mm Hg, at a ferritin threshold of > 146 ng/mL (Kim 2012).

Photo©iStockphoto.com

• A study of the relationship between increased ferritin, oxidative stress and insulin resistance in 151 healthy men revealed no threshold, only continuous increases in markers with ferritin levels from the first tertile (≤97 ng/mL) to the third (≥180 ng/mL).

Notably, the correlations remained strong and significant after adjustment for inflammation (Syrovatka 2009).

• In a 5-year study the association between ferritin levels and the incidence and

progression of carotid atherosclerosis was examined among a cohort of 826 men and women age 40 to 79 years. Serum ferritin was found to be the strongest risk factor of overall progression, and changes in ferritin levels during follow-up modified the risk with lower levels beneficial. The risk of incident carotid atherosclerosis increased linearly and doubled from quintile I (0-36 ng/mL) to quintile IV (130-222 ng/mL). When subjects with < 50 ng/mL of ferritin were compared with those ≥ 50 ng/mL, the increase in incidence of carotid atherosclerosis for elevated ferritin per 100 person years was approximately 0.3 vs. 4.8, 0.2 vs. 4.5 and 1.6 vs. 4.4 for men, premenopausal women and naturally menopausal women, respectively (Kiechl 1997).

• In a study of over 12,000 men, the ferritin threshold for increased risk of any coronary artery calcium was >257 ng/mL (Sung 2012).

• In a study of men from either northern Europe (Zutphen) or the Mediterranean south (Crete), mean ferritin levels were 134 ng/mL and 70 ng/mL, respectively. Those from Crete (70 ng/mL) had consistently lower levels of indicators of oxidative stress, higher antioxidant capacity and higher concentrations of major antioxidants than men from Zutphen (Buijsse 2007).

Ferritin thresholds and benefit in iron-lowering studies The following studies are particularly important since they appear less subject to confounding than those cited above.

• In a randomized prospective trial, iron reduction in male smokers with peripheral arterial disease (PAD) reduced the risk of death or nonfatal heart attack, such that the number needed to treat with phlebotomy over five years to prevent one acute event was only eight, a very low number and uncommon in clinical studies. Significant benefits were also seen for all cause mortality, non-fatal MI and stroke. The initial and final mean ferritin levels were 125 ng/mL and 84 ng/ mL. In a larger study in which the above was imbedded, unequivocal benefits for all cause mortality, non-fatal MI and stroke were found for iron reduction in younger individuals 4361 years of age including non-smokers, when phlebotomy reduced ferritin levels to < 70 ng/ mL (Depalma 2012, Depalma 2013).

April/May 2014 l www.ihpmagazine.com 53

1

• A controlled trial involving phlebotomy which decreased ferritin levels from a mean of 188 to 105 ng/mL for a group of men and women with the metabolic syndrome, found a decrease in systolic blood pressure from 149 to 131 mm Hg, with no change in the control group. Fasting blood glucose, HbA1c and heart rate were also significantly decreased (Houschyar 2012).

• Use of the oral prescription chelator deferiprone over nine months in patients with non-diabetic kidney disease reduced ferritin from 144 to 59 ng/mL and resulted in significant clinical improvements (Rajapurkar 2013).

• In a trial using phlebotomy in patients with peripheral artery disease, a reduction in mean ferritin levels from 122 to 74 ng/mL resulted in a significant reduction in the incidence of visceral malignancy (Zacharski 2008).

Comparison of both the above thresholds for risk and the baseline ferritin levels from which lowering produced benefit reveals an incompatibility with the commonly used reference range values regarded as normal and of no concern.

Iron stores reductions and nonalcoholic fatty liver disease Non-alcoholic fatty liver disease (NAFLD) starts with simple hepatic steatosis and can progress to non-alcoholic steatohepatitis (NASH). One hypothesis for the pathogenesis of this disorder is the involvement of iron in increased oxidative stress and liver inflammation (Nelson 2012). High ferritin levels have been found independently associated with advanced hepatic fibrosis (Kowdley 2012). The following iron depletion studies are thus of interest.

• A study of phlebotomy on an insulin resistant group of patients with NAFLD and markedly

DONATION HISTORY PER YEAR 0 2 3 4

FERRITIN FERRITIN MEDIAN RANGE 5-95 PCT* 137 46-396 44 17-122 38 14-110 31 12-91

* 5th to 95th percentile 54 www.ihpmagazine.com l April/May 2014

elevated ferritin levels showed a significant reduction in insulin resistance (HOMA-IR decreased from 4.81 to 3.12) when ferritin levels were reduced from 438 to 52 ng/mL. More importantly, alanine transaminase (ALT) decreased from a mean of 58.1 to near normal 34.3 IU/L (Valenti 2007).

• A study examined the effect of phlebotomy in either carbohydrate intolerant subjects or type 2 diabetics, including some also diagnosed with NAFLD based on elevated ALT and ultrasound evidence of steatosis (Facchini 2002). The NAFLD and nonNAFLD groups had baseline mean ferritin levels of 299 and 220 ng/mL, respectively.

Phlebotomy produced near iron depletion (ferritin 31-15 ng/mL) and ALT fell from 61 to 32 IU/L in the NAFLD group. There were insignificant ALT changes observed in the NAFLD-free group.

• In a study where ferritin levels were manipulated with diet, 12 patients with NASH were placed on a calorie, fat and iron restricted diet. Baseline mean ferritin levels were 280 ng/mL initially and 128 ng/mL at 6 months of intervention. ALT levels decreased

The Journal of IHP from 104 to 42 IU/L over the same period.

Large changes were also seen in aspartate aminotransferase (AST) levels (Yamamoto 2007)

Iron and oxidative damage Urinary 8-hydroxydeoxyguanosine (8-OHdG) is a reliable and frequently used biomarker of systemic oxidative DNA damage (Nakano 2003, Valko 2006). The following studies are of particular interest because of the apparent absence of a threshold for adverse effects of iron.

For over 500 healthy Japanese aged 21-67, linear correlations between 8-OHdG and ferritin were found, with Spearmen rank correlation coefficients of 0.47, 0.76 and 0.73 for men overall, women aged less than 50, and women 50 years or older, respectively. These strong correlations were essentially unchanged after adjustment for potential confounders.

Subjects exhibited a large range of ferritin levels from near iron depletion to around 300 ng/mL for men and 100 ng/mL for women (Hori 2010).

For a cohort of 2500 healthy individuals aged 22 to 89 years, a smooth, almost linear 2.5 fold increase in 8-OHdG was found for men as ferritin ranged from 10 ng/mL to about 300 ng/mL. For women, 8-OHdG was increased by a factor of 3 for ferritin levels ranging from below 9 to 160 ng/mL (Nakano 2003). These results suggest no threshold and this observation is consistent with a study of vascular function and ferritin levels (Zheng 2005), and a study of oxidative stress and insulin resistance (Syrovatka 2009).

In addition, a study of ferritin lowering with phlebotomy was found to reduce 8-OHdG in patients with chronic hepatitis C (Kato, 2001).

Another study found a beneficial impact of reducing iron stores to near depletion on the development of hepatocellular carcinoma (HCC) from chronic hepatitis C (Kato 2007).

In both studies, final ferritin levels were about 10 ng/mL.

Influence of blood donation on ferritin levels Blood donation typically removes 450-500 mL per visit. The following results from a large sample of Danish men 30 to 66 years of age illustrate the dramatic effect of blood donation (Milman 1996).

Danish study of the influence of blood donation of serum ferritin levels (ng/mL) in men, 30-66 years of age (Milman 1996).

These data are consistent with a recent American study (Cable 2011). Thus on average three to four donations per year will result in a ferritin level mostly below 100 ng/mL with a median representing near iron depletion.

Risks associated with blood donation Blood donation is not totally free of adverse events. These include syncope, bruises and haematomas and sensory changes. Syncope is rare even among those over 40 (typically 0.05% incidence). Others, while frequently of higher incidence, are almost always transient and rarely of significance. The incidence of permanent injury has been cited as about 0.002% (Amrein 2012, Gavillet 2013, Newman 2012).

Of greater concern is the impact of frequent donations on iron status. Deferral at blood donor clinics is generally based on a finger stick haemoglobin assay with a commonly used threshold for deferral of < 12.5 g/dL, a threshold that has been questioned (Cable 2011). The common lower limit for normal is 13.5 g/dL, and served as the older cut-off for deferral. A 12- month multicenter donor clinic follow-up study examined the iron status in blood donors screened by finger stick. The threshold for diagnosing unacceptable iron stores was a ferritin level < 12 ng/mL. This was found in 15% of those passing the haemoglobin screening. The finger stick haemoglobin test is evidently not excluding some individuals with low iron status and thereby increasing the risk of an adverse impact of donation. For frequent blood donors, an annual ferritin test and if appropriate, a follow-up test for iron deficient erythropoiesis are indicated (Cable 2011).

Conclusions It is clear from the above studies that the serum ferritin thresholds for the appearance of risk and the baseline values from which lowering produces benefit are predominantly well below the upper reference range values for normal, and in fact more closely correspond to population 50th percentiles. Indeed, lowering ferritin to levels far below the 50th population percentile produces significant benefit associated with severity of a variety of disorders. In some studies, this is observed even when the baseline level for lowering April/May 2014 l www.ihpmagazine.com 55

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is already quite low. The DNA oxidative stress studies strongly support the view that the optimum ferritin level is one representing near iron depletion, which can only be easily achieved by blood donation or phlebotomy. This conclusion challenges a widely held belief that ferritin anywhere in the normal reference range should not cause concern.

References Adams,P.C. Diabetes: Serum ferritin levels and T2DM--are body iron stores elevated? Nat Rev Endocrinol 2012; 8(10): 573-575.

Adams,P.C. and Barton,J.C. A diagnostic approach to hyperferritinemia with a nonelevated transferrin saturation. J Hepatol. 2011; 55(2): 453-458.

Amrein,K., Valentin,A., Lanzer,G. and Drexler,C. Adverse events and safety issues in blood donation--a comprehensive review. Blood Rev 2012; 26(1): 33-42.

Buijsse,B., Feskens,E.J., Moschandreas,J., Jansen,E.H., Jacobs,D.R., Jr., Kafatos,A., Kok,F.J. and Kromhout,D. Oxidative stress, and iron and antioxidant status in elderly men: differences between the Mediterranean south (Crete) and northern Europe (Zutphen). Eur J Cardiovasc Prev Rehabil. 2007; 14(4): 495-500.

Cable,R.G., Glynn,S.A., Kiss,J.E., Mast,A.E., Steele,W.R., Murphy,E.L., Wright,D.J., Sacher,R.A., Gottschall,J.L., Vij,V. and Simon,T.L. Iron deficiency in blood donors: analysis of enrollment data from the REDS-II Donor Iron Status Evaluation (RISE) study.

Transfusion 2011; 51(3): 511-522.

Choi,K.H., Park,M.S., Kim,J.T., Nam,T.S., Choi,S.M., Kim,B.C., Kim,M.K. and Cho,K.H. The serum ferritin level is an important predictor of hemorrhagic transformation in acute ischaemic stroke. Eur J Neurol 2012; 19(4): 570-577.

Depalma,R.G. and Zacharski,L.R. Iron reduction benefits: positive results from a “negative” prospective randomized controlled trial. Vasc Endovascular. Surg 2012; 46(7): 596-597.

Depalma,R.G., Zacharski,L.R., Chow,B.K., Shamayeva,G. and Hayes,V.W. Reduction of iron stores and clinical outcomes in peripheral arterial disease: outcome comparisons in

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smokers and non-smokers. Vascular 2013.

Facchini,F.S., Hua,N.W. and Stoohs,R.A. Effect of iron depletion in carbohydrate-intolerant patients with clinical evidence of nonalcoholic fatty liver disease. Gastroenterology 2002; 122(4): 931-939.

Gavillet,M., Tissot,J.D. and Canellini,G. Blood donation associated risks: data from a Swiss regional haemovigilance program. Transfus. Med 2013; 23(4): 269-271.

Haidari,M., Javadi,E., Sanati,A., Hajilooi,M. and Ghanbili,J. Association of increased ferritin with premature coronary stenosis in men. Clin Chem 2001; 47(9): 1666-1672.

Holay,M.P., Choudhary,A.A. and Suryawanshi,S.D. Serum ferritin-a novel risk factor in acute myocardial infarction. Indian Heart J 2012; 64(2): 173-177.

Hori,A., Mizoue,T., Kasai,H., Kawai,K., Matsushita,Y., Nanri,A., Sato,M. and Ohta,M. Body iron store as a predictor of oxidative DNA damage in healthy men and women. Cancer Sci 2010; 101(2): 517-522.

Houschyar,K.S., Ludtke,R., Dobos,G.J., Kalus,U., Broecker-Preuss,M., Rampp,T., Brinkhaus,B. and Michalsen,A. Effects of phlebotomy-induced reduction of body iron stores on metabolic syndrome: results from a randomized clinical trial. BMC Med 2012; 10: 54.

Kato,J., Kobune,M., Nakamura,T., Kuroiwa,G., Takada,K., Takimoto,R., Sato,Y., Fujikawa,K., Takahashi,M., Takayama,T., Ikeda,T. and Niitsu,Y. Normalization of elevated hepatic 8-hydroxy2’-deoxyguanosine levels in chronic hepatitis C patients by phlebotomy and low iron diet. Cancer Res 2001; 61(24): 8697-8702.

Kato,J., Miyanishi,K., Kobune,M., Nakamura,T., Takada,K., Takimoto,R., Kawano,Y., Takahashi,S., Takahashi,M., Sato,Y., Takayama,T. and Niitsu,Y. Long-term phlebotomy with lowiron diet therapy lowers risk of development of hepatocellular carcinoma from chronic hepatitis C. J Gastroenterol 2007; 42(10): 830-836.

Kiechl,S., Willeit,J., Egger,G., Poewe,W. and Oberhollenzer,F. Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Circulation 1997; 96(10): 3300-3307.

The Journal of IHP Kim,M.K., Baek,K.H., Song,K.H., Kang,M.I., Choi,J.H., Bae,J.C., Park,C.Y., Lee,W.Y. and Oh,K.W. Increased serum ferritin predicts the development of hypertension among middle-aged men. Am J Hypertens. 2012; 25(4): 492-497.

Syrovatka,P., Kraml,P., Potockova,J., Fialova,L., Vejrazka,M., Crkovska,J. and Andel,M. Relationship between increased body iron stores, oxidative stress and insulin resistance in healthy men. Ann Nutr Metab 2009; 54(4): 268-274.

Kowdley,K.V., Belt,P., Wilson,L.A., Yeh,M.M., Neuschwander-Tetri,B.A., Chalasani,N., Sanyal,A.J. and Nelson,J.E. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 2012; 55(1): 77-85.

Valenti,L., Fracanzani,A.L., Dongiovanni,P., Bugianesi,E., Marchesini,G., Manzini,P., Vanni,E. and Fargion,S. Iron depletion by phlebotomy improves insulin resistance in patients with nonalcoholic fatty liver disease and hyperferritinemia: evidence from a case-control study. Am J Gastroenterol 2007; 102(6): 1251-1258.

Lee,D.H. and Jacobs,D.R., Jr. Serum markers of stored body iron are not appropriate markers of health effects of iron: a focus on serum ferritin.

Med Hypotheses 2004; 62(3): 442-445.

Mainous,A.G. and Diaz,V.A. Relation of serum ferritin level to cardiovascular fitness among young men. Am J Cardiol 2009; 103(1): 115-118.

Milman,N. Serum ferritin in Danes: studies of iron status from infancy to old age, during blood donation and pregnancy. Int J Hematol 1996; 63(2): 103-135.

Nakano,M., Kawanishi,Y., Kamohara,S., Uchida,Y., Shiota,M., Inatomi,Y., Komori,T., Miyazawa,K., Gondo,K. and Yamasawa,I. Oxidative DNA damage (8-hydroxydeoxyguanosine) and body iron status: a study on 2507 healthy people. Free Radic Biol Med 2003; 35(7): 826-832.

Nelson,J.E., Klintworth,H. and Kowdley,K.V. Iron metabolism in Nonalcoholic Fatty Liver Disease.

Curr Gastroenterol Rep 2012; 14(1): 8-16.

Newman,B. and Siegfried,B. Syncope after whole blood donation: factors associated with increased donor injury. Transfusion 2012; 52(1): 210-211.

Rajapurkar,M.M., Hegde,U., Bhattacharya,A., Alam,M.G. and Shah,S.V. Effect of deferiprone, an oral iron chelator, in diabetic and nondiabetic glomerular disease. Toxicol Mech Methods 2013; 23(1): 5-10.

Sung,K.C., Kang,S.M., Cho,E.J., Park,J.B., Wild,S.H. and Byrne,C.D. Ferritin is independently associated with the presence of coronary artery calcium in 12,033 men.

Arterioscler Thromb Vasc Biol 2012; 32(10): 2525-2530.

Valko,M., Rhodes,C.J., Moncol,J., Izakovic,M. and Mazur,M. Free radicals, metals and antioxidants in oxidative stress-induced cancer.

Chem Biol Interact. 2006; 160(1): 1-40. van der A,D., Grobbee,D.E., Roest,M., Marx,J.J., Voorbij,H.A. and Van der Schouw,Y.T. Serum ferritin is a risk factor for stroke in postmenopausal women. Stroke 2005; 36(8): 1637-1641.

Ware,W.R. Iron and diabetes. Integrative Healthcare Practitioners 2013;(September): 76-81.

Yamamoto,M., Iwasa,M., Iwata,K., Kaito,M., Sugimoto,R., Urawa,N., Mifuji,R., Konishi,M., Kobayashi,Y. and Adachi,Y. Restriction of dietary calories, fat and iron improves nonalcoholic fatty liver disease. J Gastroenterol Hepatol. 2007; 22(4): 498-503.

Zacharski,L.R., Chow,B.K., Howes,P.S., Shamayeva,G., Baron,J.A., Dalman,R.L., Malenka,D.J., Ozaki,C.K. and Lavori,P.W. Decreased cancer risk after iron reduction in patients with peripheral arterial disease: results from a randomized trial. J Natl Cancer Inst 2008; 100(14): 996-1002.

Zacharski,L.R., Ornstein,D.L., Woloshin,S. and Schwartz,L.M. Association of age, sex, and race with body iron stores in adults: analysis of NHANES III data. Am Heart J 2000; 140(1): 98-104.

Zheng,H., Cable,R., Spencer,B., Votto,N. and Katz,S.D. Iron stores and vascular function in voluntary blood donors. Arterioscler Thromb Vasc Biol 2005; 25(8): 1577-1583.

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The HypothalamusPituitary-Adrenal Axis Role in Borderline Personality Disorder

By Tanya Lee, ND Abstract Health Centre of Milton 420 Main St. East Unit 102 & 103 Milton ON L9T 1P9 info@healthcentreofmilton.ca

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Borderline personality disorder (BPD) is an axis II mental health disorder characterized by a series of symptoms which consists of recurrent patterns of emotional instability, strained interpersonal relationships, poor self-image and compromised inhibitory/impulse control. It is thought to affect between 1.4 to 6.0% of the population. The role of disrupted function of the hypothalamus-pituitary-adrenal (HPA) axis is an area of growing interest with respect to the pathophysiology of BPD. Overall, there is conflicting data on whether patients with uncomplicated BPD show significantly different HPA axis responsiveness compared to healthy controls, however more consistent patterns seem to emerge when evaluating BPD patients with secondary psychiatric cormorbidities.

BPD patients with comorbid MDD appear to have increased cortisol levels at baseline and in response to stress, perhaps due to decreased sensitivity of the negative feedback system. BPD patients with comorbid PTSD appear to have lower levels of cortisol, indicating either cortisol hyper-suppression, or adrenal hypofunction. Treatments with the aim of regulating HPA axis responsiveness may be of benefit among this patient population.

The Journal of IHP Borderline Personality Disorder Borderline personality disorder (BPD) is an axis II mental health disorder that has been found to be over-represented in psychiatric outpatient settings (DixonGordon 2013). Its prevalence in the United States is estimated at between 1.4 % and 6.0% (Dixon-Gordon 2013, Ishak 2013), and currently there are no accurate rates of prevalence for the Canadian population (CAMH 2009). BPD is a personality disorder characterized by a series of symptoms which consists of recurrent patterns of emotional instability, strained interpersonal relationships, poor self-image and compromised inhibitory/impulse control (Carvalho 2013, Dixon-Gordon 2013, Lyons-Ruth 2011, Zimmerman 2009). Self-harm and increased suicide risk are also common features of BPD (Fox 2014). Research suggests that early life stressors are a major risk factor in the development of BPD, lending to a growing interest in the role of hypothalamus-pituitary-adrenal axis (HPA) disruption in the etiology of BPD (Carvalho 2012, Carvalho 2013, Zanarini 1997, Zimmerman 2009). This article will review current evidence pertaining to the role of the HPA-axis in BPD. Conventional treatment for BPD focuses primarily on psychological treatments, such as Dialectical Behavioural Therapy and Cognitive Behavioural Therapy, and pharmacological therapy including use of mood stabilizers, small dose atypical antispsychotics, and antidepressants, all of which have been shown to improve the quality of life in BPD patients (Fox 2014, Ishak 2013). Due to the nature of their symptoms, in fact, BPD patients may be over-dependent on the healthcare system. A study performed by Zanarini et. al outlines the overuse of treatments available to BPD patients, such as therapy, psychiatric hospitalizations, and standing medications by BPD patients, compared to other axis II controls.

Researchers found that 50-60% of BPD patients had participated in selfhelp groups, had numerous psychiatric hospitalizations, and/or day or residential treatments. Approximately 30-35% had been in either group, individual, and/or couples/family therapy, or had received

intensive polypharmacy treatment (Zanarini 2001). There is a need for new strategies to enhance symptom management in this area.

Due to the complex nature of BPD, research in this area is striving to uncover new mechanisms involved in BPD, in order to improve treatment strategies that could result in more effective symptom management and enhanced quality of life for BPD patients. An area of emerging interest is the role of HPA-axis function on the pathophysiology of BPD; in this paper, we will assess the current evidence in this regard.

Hypothalamus-Pituitary-Adrenal Axis The hypothalamus-pituitary-adrenal (HPA) axis is comprised of the hypothalamus, anterior pituitary, and adrenal cortex. This system regulates and controls the body’s response to external and internal stress by activating the commonly known “fight or flight” response. In response to a “stressor”, the hypothalamus secretes corticotropinreleasing hormone (CRH), which activates the anterior pituitary to release adrenocorticotropic hormone (ACTH), which in turn stimulates the adrenal cortex to release cortisol. Once optimal cortisol levels have concentrated the blood, this in turn activates the negative feedback system to inhibit the release of CRH from the hypothalamus, shutting down further release of hormones at all levels (Jones 2011, Zimmerman 2009). Impaired negative feedback is one of the possible problems that can occur with HPA-axis disruption.

Cortisol itself has also been an important focus as a biological mediator of psychiatric illness; conditions of hypercortisolemia, (i.e. Cushing’s syndrome), and hypocortisolemia (i.e.

Addison’s disease) have both been associated with mental health symptoms such as anxiety, depression, and irritability (Sonino 1998). CRH has been found to be the stress-initiating hormone in the HPA axis; in vivo studies have shown CRH administration induces anxiety-like behaviour, such as increased emotional reactivity, withdrawal, increased motor

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activity and decreased social interaction in mice (Dunn 1990). Therefore, chronically elevated or depressed cortisol production by the adrenal cortex is another possible source of HPA-axis dysfunction.

HPA axis Function in BPD A number of studies have found altered patterns in the HPA axis in BPD patients. Lieb et. al performed a study that measured salivary cortisol collected from 23 un-medicated female patients with BPD, and 24 healthy female controls, during ambulatory conditions. On days one and two, cortisol levels in response to awakening were determined in four-15 minute intervals.

A low dose dexamethasone suppression test (DST, 0.5mg of dexamethasone) was administered after the last salivary sample on day two in order to assess the level of cortisol suppression on day three. Results found that patients with BPD displayed higher levels of cortisol compared to healthy controls during days one and two as well and day three. This study suggest that BPD may have increased cortisol output compared to healthy controls, perhaps through lowered sensitivity of the HPA axis negative feedback system (Lieb 2004).

Other recent studies have shown similar results. A study performed by Lyons-Ruth et. al compared salivary cortisol levels in 17 BPD females and 15 non-BPD females in response to a conflict discussion with their mothers. Results found that not only were cortisol levels higher in BPD patients anticipating the conflict discussion, BPD patients also reported higher levels of distress, post discussion compared to non-BPD patients (Lyons-Ruth 2011). Scott et. al found that women with BPD had higher baseline cortisol levels as well as higher subjective negative affect at baseline and in response to stress, compared to two control groups consisting of non-BPD patients; 1) trait-match controls (specifically on impulsivity and negative affect) and non-trait matched controls. Interestingly, this study found attenuated cortisol levels in response to stress (Scott 2013). Increased baseline cortisol levels, but attenuated cortisol levels in response to stress have been demonstrated in earlier studies. A study by Nater et. al confirmed this pattern of cortisol, but also found that ACTH and the catecholaminergic response were no different in BPD patients compared to controls (Nater 2010). This suggests that patients with BPD may have higher baseline cortisol levels, but lower cortisol response 60 www.ihpmagazine.com l April/May 2014

The Journal of IHP

to endogenous ACTH, or stress, possibility pointing to hypofunctioning of cortisol secretion by the adrenal glands, or perhaps hypersuppression of cortisol caused by a dysfunction of the negative feedback system.

The Influence of Comorbid Psychiatric Conditions The pattern of HPA axis function in BPD is yet to be established, with the majority of studies producing rather inconsistent results. It is possible that factors other than simply a BPD diagnosis may contribute to HPA axis regulation in BPD. BPD is strongly associated with comorbidity with other psychiatric health conditions (Zimmerman 2009, Lange 2005).

The most common clinical conditions that have been found to be associated with HPA dysregulation include major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and eating disorders, which occur at high rates in those with BPD (Carvalho 2012, Morris 2014, Rosenberg 2013, Wingenfeld 2013, Zimmerman 2009). In 2009, Zimmerman et. al performed a review of 18 studies published between 1950-2007. The review found that dysfunction of the HPA axis is an apparent feature in BPD based on four assessment methods used: 1) assessment of baseline cortisol levels, 2) cortisol response to the dexamethasone-suppression test (DST), 3) cortisol and ACTH response to the combined dexamethasone (DEX)- CRH test, and 4) cortisol response to psychosocial stressors. Results typically found no difference in HPA axis function in BPD patients when compared to healthy controls, with only two studies showing non-suppression of cortisol in BPD patients in the using the DST method. However, HPA axis dysfunction was more commonly linked to BPD in the presence of comorbid conditions and trauma history.

et. al also showed this paradoxical response: BPD patients with PTSD showed increased suppression of cortisol when administered 0.5 mg of DEX, whereas patients with comorbid MDD and healthy controls did not demonstrate hypersuppression (Lange 2005).

Another study performed by Wingenfeld et. al found that patients with BPD or BPD+PTSD had improved (autobiographical) memory when administered cortisol, whereas this memory-enhancing response to cortisol did not occur in patients with BPD+MDD (Wingenfeld 2013).

HPA axis function in BPD + MDD Increased cortisol secretion has been established as a hallmark feature of MDD (Carvalho 2012, Schatzberg 2013), a condition often preceded by periods of chronic, or traumatic, episodic stress (Hammen 2005, Lee 2002).

A recent study by Morris et. al found that patients diagnosed with MDD showed increase cortisol levels

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Interestingly, Zimmerman et. al. found an apparent distinction in HPA response based on the type of comorbidity present (2009). There was a paradoxical response of the HPA axis among BPD patients with either comorbid MDD or PTSD. BPD patients with comorbid MDD were found to be have impaired negative feedback inhibition of cortisol (nonsuppression) at a rate of 16-73% when administered a 1.0 mg dose of DEX. Alternately, BPD patients with comorbid PTSD showed to have elements of enhanced negative feedback (hyper-suppression) of cortisol in response to 0.5 mg dose of DEX. Patients with high level of dissociative symptoms showed increased response to psychosocial stressors, and BPD patients with a strong history of childhood abuse demonstrated increased ACTH release levels on CRH stimulation (Zimmerman 2009). A study performed by Lange April/May 2014 l www.ihpmagazine.com 61

during the depressive episode, as well as during recovery, when compared to controls, who showed habituation of cortisol levels in response to stress (Morris 2014). Non-suppression of cortisol, or hypersecretion, among in BPD patients with comorbid MDD was also a pattern identified by Zimmerman et. al in their review (2009). A more recent study by Carvalho et. al found that patients with BPD and patients with MDD showed increased basal cortisol levels as well as higher post-DEX (0.5 mg) cortisol levels compared to healthy controls. The degree of increase was positively correlated with symptom severity, level of dissociation, and past history of childhood abuse (Carvalho 2012). Interestingly, this study did not find that increased cortisol levels was a result of impaired negative feedback in response to low dose DEX administration, as hypothesized (Carvalho 2012). Instead, these findings suggest that a history of exposure to chronic stress, characteristic of MDD, may be the reason for increased cortisol levels in BPD patients.

HPA axis function in BPD + PTSD PTSD is a condition triggered by exposure to acutely traumatic events. Characteristics of PTSD can be explained through symptom clusters comprised of avoidance, numbing, separating, dysphoric- and anxious- arousal (Horn 2014). The review by Zimmerman et. al., along with other studies, found that patients with BPD who display comorbid PTSD demonstrated elements of HPA hyper-suppression, or enhanced negative feedback on cortisol, ultimately resulting in lower cortisol levels (Lange 2005, Zimmerman 2009). A recent study performed by Horn et. al compared the cortisol response to trauma among that adults with PTSD or healthy adult controls (2014). Not surprisingly, the adults with PTSD had significantly lower cortisol levels compared to healthy controls, consistent with findings outlined in the Zimmerman review (Horn 2014). A crossover study by Carvalho et. al. showed similarly consistent results, finding that divergent responses in HPA axis function upon comparing patients with BPD and BPD+PTSD. A total of 32 female patients with BPD and 32 healthy females were both given 10mg of hydrocortisone. They were then required to perform an adapted emotional go/no-go paradigm to assess response times to emotional face stimuli. It was found that both BPD and healthy controls displayed quicker reaction times to target stimuli when administered hydrocortisone, while BPD patients with comorbid PTSD displayed longer reaction times (Carvalho 2013).

In a recent study, Dixon-Gordon et. al investigated the relationship between BPD and emotional reactivity to a stressor in subjects with comorbid PTSD through subjective assessment and cortisol measurement (2013). Results showed that BPD patients with low-

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The Journal of IHP level PTSD symptoms had a rapid onset of cortisol secretion in response to a stressor. However, those with more severe PTSD showed results consistent with previous findings: no change in cortisol in response to stress (Dixon-Gordon 2013). This study suggests that the reason for hyper-suppression of cortisol found in BPD patients with comorbid PTSD could be explained through emotional “numbing”, or allostatic load, a compensatory method for patients exposed to chronic stress/arousal of the HPA axis, typical to patients with PTSD (Jones 2011). Rather than a normal level of cortisol released in response to stress, the chronic stress and trauma experienced by a PTSD patient may place an excessive demand in the HPA axis, thereby creating HPA axis hypo-functioning over time (Horn 2014, Daskalakis 2013, Jones 2011). This may be a result of decreased synthesis of hormones, down-regulation of receptors in the pituitary glands, decreased cortisol (glucocorticord) sensitivity, or hyposecretion of cortisol by the adrenal glands, as a protective mechanism to subvert negative effects of prolonged exposure to cortisol to the body (Jones 2011); however exact mechanisms are still unclear and require more research. These studies nonetheless provide strong evidence that PTSD comorbidity may be the cause of cortisol hyper-suppression in patients with BPD. Discussion Investigations of HPA axis function in patients with BPD have produced variable results. While it appears that patients with BPD may generally exhibit altered HPA axis function, with the primary feature being increased baseline cortisol levels (Carvalho 2012, Lieb 2004), there is not yet sufficient evidence to definitively support altered HPA axis function in patients with BPD upon comparison with healthy controls (Carvalho 2013, Zimmerman 2009). Reasons for such varied results in HPA axis function in uncomplicated BPD could be due to failure to account for a number of variables. HPA axis function is easily influenced by age, gender, time of menstrual cycle, personal sleep/wake cycles, and nutritional status (Borsonelo 2011, Panagiotakopoulos 2014, Woods 2013). In addition, collection of cortisol samples can influence levels, as fear of needles can increase cortisol levels, and salivary cortisol collection can be altered by the presence of food particles in the saliva (Zimmerman 2009). Altered HPA function does appear to be more obvious in BPD patients in the presence of psychiatric comorbidities, most notably MDD and PTSD, (Carvalho 2012). BPD patients with comorbid MDD appear to have increased cortisol levels at baseline and in response to stress, perhaps due to decreased sensitivity of the negative feedback system. BPD patients with comorbid PTSD appear to have lower levels of cortisol, indicating either cortisol hyper-suppression, or adrenal hypofunction. These features are not unique to these comorbidities only in combination with BPD, but also have been demonstrated among patients with uncomplicated MDD and PTSD, independent of BPD. It is possible that while HPA axis function may not play a major role in the etiology of BPD, the presence of other psychiatric conditions contribute to altered HPA axis function. Nonetheless, current research does support possible low-grade alterations of HPA axis function in patients with BPD, suggesting that treatments focused on regulation of HPA axis may be of benefit to these patients, especially when BPD is associated with comorbid conditions, such as PTSD and MDD.

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Leonard BE. Serotonin receptors and their function in sleep, anxiety disorders and depression. Psychother Psychosom. 1996 Mar-Apr;65(2):66-75.

Lieb K, Rexhausen JE, Kahl KG, Schwieger U, Philipsen A, Hellhammer DH, et al. Increased diurnal salivary cortisol in women with borderline personality disorder.

Journal of Psychiatric Research 2004;38:559–65.

Lyons-Ruth K, Choi-Kain L, Pechtel P, Bertha E, Gunderson J. Perceived parental protection and cortisol responses among young females with borderline personality disorder and controls. Psychiatry Res. 2011 Oct 30;189(3):426-32.

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Rosenberg N, Bloch M, Ben Avi I, Rouach V, Schreiber S, Stern N, Greenman Y. Cortisol response and desire to binge following psychological stress: comparison between obese subjects with and without binge eating disorder.

Psychiatry Res. 2013 Jul 30;208(2):156-61.

Scott LN, Levy KN, Granger DA. Biobehavioral reactivity to social evaluative stress in women with borderline personality disorder. Personal Disord. 2013 Apr;4(2):91-100.

Schatzberg AF, Keller J, Tennakoon L, Lembke A, Williams G, Kraemer FB, Sarginson JE, Lazzeroni LC, Murphy GM. HPA axis genetic variation, cortisol and psychosis in major depression. Mol Psychiatry. 2013 Oct 29.

Wingenfeld K, Driessen M, Terfehr K, Schlosser N, Fernando SC, Otte C, Beblo T, Spitzer C, Löwe B, Wolf OT. Effects of cortisol on memory in women with borderline personality disorder: role of co-morbid posttraumatic stress disorder and major depression. Psychol Med. 2013 Mar;43(3):495-505.

Woods DL, Kim H, Yefimova M. To nap or not to nap: excessive daytime napping is associated with elevated evening cortisol in nursing home residents with dementia.

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The Journal of IHP

NEM

®

Novel Joint Care Supplement By Christopher Habib, ND Christopher Habib, ND Clinic Director Mahaya Forest Hill 102-73 Warren Road Toronto, ON M4V 2R9 info@chrishabibnd.com

Abstract Natural Eggshell Membrane (NEM®) is a relatively novel supplement that has been used to treat osteoarthritis as well as joint and connective tissue disorders. There is in vitro evidence that NEM® suppresses tumor necrosis factor-alpha production in peripheral blood mononuclear cell cultures, thus indicating a potentially promising anti-inflammatory action in humans. However, the amount of human clinical research conducted on NEM® is limited and the majority of the supportive data is derived from one group of researchers. The natural product industry has embraced NEM® with open arms and incorporated it into many supplements for joint health. This article reviews the four human studies conducted on NEM® to date in chronological order of publication. The first study reviewed was a combination of two pilot studies that demonstrated significant treatment responses. However, it suffered from limited enrollment and no placebo-control. The second study reviewed had a high drop-out rate, but calculated that one out of every five patients should experience a 50% pain reduction within 30 to 60 days. The third study reviewed had significant methodological flaws and demonstrated that NEM® only had an effect on post-exercise pain.

The fourth study reviewed was pre-publication so the data are not described, but they showed positive results. Although more evidence is certainly warranted, the studies available lend support to the notion that NEM® is safe and effective. NEM® may serve as an alternative recommendation for patients suffering from joint pain.

April/May 2014 l www.ihpmagazine.com 65

3

Introduction Natural Eggshell Membrane (NEM®) is a relatively novel supplement that has been used to treat osteoarthritis as well as joint and connective tissue disorders (Ruff 2009). NEM® contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy articular cartilage. The outer membrane is made of type I collagen and the inner membrane consists of type V collagen (Wong 1984). Type X collagen is also reported to occur in both these membrane structures (Arias 1991). There is in vitro evidence that NEM® suppresses tumor necrosis factor-alpha production in peripheral blood mononuclear cell cultures, thus indicating a potentially promising anti-inflammatory action in humans (Benson 2012). In addition, recent rat studies have demonstrated that oral supplementation with NEM® can also influence later-phase cytokines such as MCP-1, MIP-1α & β, RANTES and VEGF (Ruff 2014).

Toxicological studies have shown that oral supplementation in rats up to 2000mg/kg body weight repeated daily for 90 days did not cause any signs of toxicity via multiple evaluation methods (Ruff 2012). However, the amount of human clinical research conducted on NEM® is limited and the majority of the supportive data is derived from one group of researchers.

As such, it is imperative that the methodology

66 www.ihpmagazine.com l April/May 2014

and results of these trials be analyzed with scrutiny and put into context.

The natural product industry has embraced NEM® with open arms and incorporated it into many supplements for joint health. Although the trials that are available are promising, it is important for health practitioners to analyze the validity of the research available before implementing new potential therapies with patients. This article will review the four human studies conducted on NEM® to date in chronological order of publication. Although more evidence is certainly warranted, the studies available currently lend support to the notion that NEM® is both safe and effective.

STUDY ONE (2009) Initially, two pilot clinical studies were conducted that evaluated the efficacy of NEM® for the relief of the pain and discomfort associated with joint and connective tissue disorders (Ruff 2009). To be eligible to participate, subjects must have had persistent pain lasting at least three months associated with a joint or connective tissue disorder, with a minimum baseline pain level of 2 on a 0 to 10 analog Likert scale (with 0 equating to no pain and 10 equating to the most severe pain).

If currently taking medication, subjects had to undergo a washout period beforehand. Each

The Journal of IHP study lasted for one month. The studies were single center, open-label, and controlled. One trial was single-arm and the other was doublearm. Subjects suspended all current pain relief medications to participate in the study. For the double-arm trial, eligible subjects were randomized to either NEM® formulation X or Y. These two formulations differed in the degree to which they were partially hydrolyzed prior to final ingredient blending (Y approximately 2.5 times more than X).

It is important to note that the investigators were not blinded to treatment (as both studies were open-label), or to randomization (in the double-arm trial). The subjects were blinded to randomization in the double-arm trial.

The treatments consisted of a once daily supplementation of either NEM® in the singlearm trial, or the two different formulations of NEM® in the double-arm trial, provided in 500mg vegetarian capsules. Subjects visited the clinic at seven and 30 days following the onset of treatment. Compliance was checked by interview and by counting unused doses.

Acetaminophen was allowed for pain relief rescue and subjects had to record the time and amount taken in diaries. In the single-arm and double-arm trials, the primary outcome measure was mean effectiveness of NEM® in relieving general pain, and secondary outcome measures were joint flexibility and range-of-motionassociated (ROM) pain. The Likert scale was used during the seven and 30 day clinical assessments.

In the single-arm trial, 11 subjects were enrolled and 10 of them completed the study protocol.

For those that completed the study protocol, compliance was over 98%. The mean baseline pain value was 3.6 ± 1.8; the mean flexion ROM was 64.2° ± 36.5°; and the mean ROMassociated pain was 2.9 ± 2.6. Supplementation with NEM® produced a significant response at seven days for flexibility, as a 27.8% increase.

At 30 days, there was a significant response for general pain (as a 72.5% reduction), an increase in flexibility (43.7% from baseline), and an improvement in ROM-associated pain (75.9% reduction). Of note, nearly half of the patients in the single-arm trial reported they were pain-free (reported score of 0) by 30 days of

supplementation. Rescue pain medication was used very rarely, only once in ever 20-22 days.

In the double-arm trial, a total of 28 subjects were enrolled. 14 subjects were randomized to NEM® X and 14 were randomized to NEM® Y. 26 subjects completed the study, as one participant in each group dropped-out due to lack of efficacy. Compliance was over 96%. Supplementation with NEM® produced a significant response at seven days for both treatment arms (X: 18.4% reduction, Y: 31.3% reduction). The researchers determined that the 12.9% difference was not large and was not clinically meaningful. At 7 days, the Y arm crossed over to the X formulation for the remainder of the study. The significant treatment response continued to 30 days for pain, with a final reduction of 30.2%.

The bottom line from this trial is that there were no adverse events reported during either of the studies and the treatment was reported to be extremely well tolerated by the study participants. The safety profile for NEM® in this study was excellent, excluding the possible concern of egg allergy. In analyzing the limitations of this study, both trials suffered from limited enrollment. The double-arm trial had dropouts due to lack of efficacy. Both trials were open label, thus there is the possibility that the positive outcomes are largely due to a placebo response. The lack of investigator blinding and the fact that two of the main investigators are employed by the sponsor of the study could have further exaggerated any positive results. Overall, this study set the stage for a larger study with some modifications to help address some of these limitations.

STUDY TWO (2009) The second and arguably more important study to examine is a randomized, double-blind, multicenter, placebo-controlled trial, known as OPTION, or Osteoarthritis Pain Treatment IncorpOrating NEM® (Ruff 2009). This study utilized subjects that suffered from symptomatic osteoarthritis of the knee. Similar to the pilot trials, subjects were required to suspend all current pain medication in order to participate.

This time, subjects were randomized to receive either NEM® or placebo, using a permuted-

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3

block randomization table consisting of four subjects per block. All parties were blinded to the treatment. The treatment used was a once daily oral dose of NEM速 or placebo. Clinic visits took place at 10, 30, and 60 days following the onset of treatment. Compliance was checked in a similar fashion as the previous study.

The primary endpoint was the measurement of the effectiveness of NEM速 in relieving pain, stiffness, and discomfort as compared to placebo. The Western Ontario and McMasters Universities (WOMAC) Osteoarthritis IndexVisual Analog Scale was used. An absolute increase in the mean response rate of 35% was considered by the authors to be a clinically meaningful treatment effect. This trial initially had 67 subjects enrolled. However, only 20 in the treatment group and 18 in the placebo group completed the study protocol, due to various issues (stringent pain management requirements, small study sample size, some drop-outs due to lack of efficacy). Compliance was measured as over 97% for those that completed the study.

After analysis, the results showed that supplementation with NEM速 produced a

68 www.ihpmagazine.com l April/May 2014

response rate ranging from 10.3% to 26.6% improvement better than placebo at all time points for both pain and stiffness (but not for function and overall WOMAC, these results were insignificant despite improvements).

The responses for pain and stiffness were rapid, occurring after only 10 days of supplementation. There were no adverse events associated with the treatment. The NNTs for at least a 50% reduction in pain at 10, 30, and 60 days were calculated. Clinically, the NNTs indicate that one out of every five patients should experience a 50% pain reduction within 30 to 60 days. For stiffness, the NNTs indicate that at 60 days, nearly one out of every two patients would experience a 50% reduction in stiffness. The limitations of this study included a limited initial enrollment, a high drop-out rate (43%), and a smaller mean treatment effect than anticipated.

STUDY THREE (2012) One study was conducted and published more recently by the company Precision Nutrition Inc. on a product containing an encapsulated version of NEM速 named Fast Joint Care+ (FJC+) (Berardi 2012). Although this study

The Journal of IHP

was not published in a peer-reviewed journal and was an independent research study, the information provided can still be examined. In this study, 60 adults experiencing chronic joint pain were supplement with FJC+ or placebo for four weeks. They completed a weekly exercise protocol that challenged their irritated joint.

Subjects then rated their joint pain immediately and one day after the exercise challenge.

The results showed that post-exercise joint pain in the FJC+ group decreased by four3. four%, while the placebo group experienced a 30.6% decrease in pain over the four weeks.

It is important to note that there were large differences in Joint Pain Index scores at baseline for the treatment group and placebo group. The FJC+ group had a baseline score within the four0-50 range (indicating more pain), while the placebo group had Joint Pain Index scores in the 20-30 range (indicating less pain). The exact numbers were not reported directly in the study. This discrepancy would set the stage for a larger potential decrease in pain for the treatment group, which is exactly what happened. This challenges the internal validity of the study. In addition, there were no significant differences in joint pain scores across the four weeks of supplementation,

indicating similar joint pain decreases in both the FJC+ group and the placebo group. Overall, this study appears to lend support to the safety of eggshell membrane, but not to its efficacy beyond immediately post-exercise.

STUDY FOUR (Pre-Publication) A fourth human trial on NEM速 has been completed by the company ESM Technologies, LLC and it is currently pre-publication (Danesch pre-publication). The trial is multicentered and open-label. It includes 44 subjects with knee and/or hip osteoarthritis. Currently, the data from this study cannot be shared publicly, but the results have been seen by this author, and permission has been given to report that the effects that were seen with NEM速 were positive.

Conclusion NEM速 is a relatively novel supplement that has been used to treat osteoarthritis as well as joint and connective tissue disorders. The total quantity of human trials on NEM速 is lacking.

The first study reviewed was a combination of two pilot studies that demonstrated significant treatment responses. However, it suffered from

April/May 2014 l www.ihpmagazine.com 69

3

limited enrollment and no placebo-control.

The second study reviewed was the OPTION study, offering the most robust data on NEM® to date. Despite a high drop-out rate (43%), this study used NNTs to calculate that one out of every five patients should experience a 50% pain reduction within 30 to 60 days. With regards to stiffness, the NNTs indicated that at 60 days, nearly one out of every two patients would experience a 50% reduction. The third study reviewed had significant methodological flaws and demonstrated that NEM® only had an effect on post-exercise pain. The fourth study reviewed was pre-publication so the data were not examined closely, but still showed positive results. Overall, all trials to date have identified that NEM® is extremely safe when taken orally, with the possible exception in cases of egg allergy. The data presented suggests rapid improvements in pain and stiffness, particularly in osteoarthritis. Further well-conducted trials will provide clearer conclusions. For the time being, NEM® serves as an alternative recommendation for patients suffering from joint pain.

Author Disclosure This author has witnessed patients reporting decreased pain after short periods of use of 500mg daily of NEM® in combination with 135mg of Boswellia serrata. Multiple patients with osteoarthritis and one case of ankylosing spondylitis reported decreased pain shortly after the initiation of treatment, while one case of rheumatoid arthritis reported no response.

This author has no competing interests.

References Arias JL, Fernandez MS, Dennis JE, Caplan AI. The fabrication and collagenous substructure of the eggshell membrane in the isthmus of the hen oviduct. Matrix.

1991;11(5):313-20.

Benson KF, Ruff KJ, Jensen GS. Effects of natural eggshell membrane (NEM) on cytokine production in cultures of peripheral blood mononuclear cells: increased suppression of tumor necrosis factor-α levels after in vitro digestion. J Med Food. 2012;15(4):360-8.

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Berardi, J. Eggshell Membrane Reduces Joint Pain. Precision Nutrition Inc. 2012. [Available Online: http://www.precisionnutrition.com/ wordpress/wp-content/uploads/2013/08/ Eggshell-Membrane_Precision-Nutrition.pdf] Danesch U, Seybold M, Rittinghausen R, Treibel W, Bitterlich N. Efficacy & Safety Study of Natural Eggshell Membrane (NEM) for the Treatment of Joint & Connective Tissue Disorders [pre-publication]. Clinical Trial Identifier NCT00750854. [Clinical Trial Information Available Online: http:// clinicaltrials.gov/show/NCT00750854] Ruff KJ, DeVore DP: Reduction of proinflammatory cytokines in rats following 7-day oral supplementation with a proprietary eggshell membrane-derived product. Modern Research in Inflammation. 2014;3:19-25.

Ruff KJ, DeVore DP, Leu MD, Robinson MA. Eggshell membrane: a possible new natural therapeutic for joint and connective tissue disorders. Results from two open-label human clinical studies. Clin Interv Aging. 2009;4:23540.

Ruff KJ, Endres JR, Clewell AE, Szabo JR, Schauss AG. Safety evaluation of natural eggshell membrane-derived product. Food Chem Toxicol. 2012;50(3-4):604-11.

Ruff KJ, Winkler A, Jackson RW, DeVore DP, Ritz BW. Eggshell membrane in the treatment of pain and stiffness from osteoarthritis of the knee: a randomized, multicenter, doubleblind, placebo-controlled clinical study. Clin Rheumatol. 2009;28(8):907-14.

Wong M, Hendrix MJ, von der Mark K, Little C, Stern R. Collagen in the egg shell membranes of the hen. Dev Biol.

1984;104(1):28-36.

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METAGENICS PHYTOMULTI PhytoMulti by Metagenics is a robust multivitamin fortified with over 20 phytonutrient extracts, including lutein, greet tea extract, and resveratrol. As such, PhytoMulti is an ideal product for use in adults in order to optimize vitamin and mineral status, in lieu of poor dietary intake or increased physiological requirements, but also provides a broad spectrum of plant nutrients in order to mimic the many health effects of a plant-based diet. The USDA MyPlate recommendations include between 9-10 servings of fruits and vegetables per day, but less than 10% of adults achieve this target (Murphy 2011).

The Mediterranean dietary pattern is an example of a well-researched diet that is very high in phytonutrients. The Mediterranean diet is associated with markedly lower risk of several chronic diseases, including cardiovascular disease and diabetes (Eustruch 2006, Interact Consortium 2011, Nordmann 2011), and a high fruit and vegetable diet has been shown to reduce risk of cancer (Block 1992), in large part due to high amounts of combined phytonutrients. Phytonutrients have been shown to confer beneficial health effects through numerous mechanisms, including modulation of signal transduction pathways, antioxidant properties, and through hormonal effects. PhytoMulti contains over 20 of these plant substances, including: lutein, zeaxanthin, acacia nilotica, and extracts of artichoke leaf, grape seed extract, green coffee, green tea, citrus bioflavonoids, resveratrol, prune skin, watercress, rosemary, pomegranate, lycopene, cinnamon, bitter melon, and blueberry.

Multivitamin supplementation has been shown to benefit a variety of physical and cognitive parameters particularly in children, pregnant women or women who may become pregnant, individuals under increased stress, individuals with poor absorption, and the elderly. In pregnancy, supplementation with a folic acid containing multivitamin has been shown to reduce risk of complications such as placental abruption, preeclampsia, in addition to decreasing risk of congenital defects including neural tube defects, anencephaly, myelomeningocele, meningocele, oral facial cleft, structural heart defects, limb defects, urinary tract anomaly, and hydrocephalus when used prior to conception and during the first trimester (Wilson 2007).

Periconceptional multivitamin use in lean women has been shown to decrease the risk of small-for-gestational-age (SGA) under the 5th percentile by up to 46% compared to non-users (OR=0.54, 95% CI), and has been associated with a 71% reduction in preeclampsia risk (OR=0.29, 95% CI) in lean women, users versus non-users (Catov 2007; Bodnar 2006). Periconceptional multivitamin use has also been associated with reduced risk of several pediatric cancers, including leukemia (OR=0.61) (39% reduced risk); pediatric brain tumors (OR=0.73) (27% reduced risk); and neuroblastoma (OR=0.53) (47% reduced risk) in a recent metaanalysis (Goh 2007).

In patients under high levels of psychological stress, use of a multivitamin has been shown improve perceived levels of stress and psychometric parameters.

Gruenwald et al (2002) found that use of a multivitamin for 6 months resulted in a 40.7% overall improvement in self rated stress levels using a psychologicalneurological questionnaire to assess “psycho-organic, central vegetative, and somatic discomforts.” Other outcomes included a 29% decrease in frequency of infections and 91% decrease in gastrointestinal discomfort. Schlebusch et al (2000) found similar benefit on various psychometric parameters in a 30 day trial (1997), and Harris found that multivitamin supplementation can improve measures of mood, stress, and alertness in older men (2011). Importantly, supplementation with a spectrum of B vitamins has also been shown to reduce ratings of workplace stress (Stough 2011).

Several trials have shown increased cognitive performance in children taking a multivitamin supplement. Benton et al (1988) found a significant increase in nonverbal intelligence in children taking a multi versus those taking placebo after 8 months’ intervention. In a 14 month study of 608 children, Vazir et al (2006) found a significant increase in attention-concentration increment scores in those supplemented with a micronutrient-fortified beverage versus those receiving placebo.

Additional benefits demonstrated in children include a reduced mean duration (5.0 versus 7.5 days, supplement versus placebo) of several common childhood illnesses including such as fever, cough and cold, diarrhea, and ear infections (Sarma 2006).

In the elderly, multivitamin supplementation has been shown to significantly improve status of such nutrients as vitamin D, vitamin B6, vitamin B12, folate, vitamin C, vitamin E, zinc, and selenium (McKay 2000; Girodon 1997). In addition, supplementation has also been found to significantly reduce rates of infection in the elderly, as found a trial in 81 subjects given various supplemental combinations of micronutrients and followed over a 2 year period (Girodon 1997).

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

Dose 2500 2500 50 60 500 60 12.50

Unit IU IU IU mg IU mcg mg

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

References Benton D, Roberts G. Lancet. 1988 Jan 23;1(8578):140-3.

Block G, et al. Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutrition and cancer 1992;18(1):1-29.

Bodnar LM, Tang G, Ness RB, Harger G, Roberts JM. Am J Epidemiol. 2006 Sep 1;164(5):470-7. Epub 2006 Jun 13.

Catov JM, Bodnar LM, Ness RB, Markovic N, Roberts JM. Am J Epidemiol. 2007 Aug 1;166(3):296-303.

Epub 2007 May 11.

Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Fertil Steril. 2008 Mar;89(3):668-76. Epub 2007 Jul 10.

Eustruch R, Martínez-González MA, Corella D, et al. Ann Intern Med. 2006 Jul 4;145(1):1-11 Girodon F, Lombard M, Galan P, Brunet-Lecomte P, Monget AL, Arnaud J, Preziosi P, Hercberg S. Ann Nutr Metab. 1997;41(2):98-107.

Goh YI, Bollano E, Einarson TR, Koren G. Clin Pharmacol Ther. 2007 May;81(5):685-91. Epub 2007 Feb 21.

Grieger JA, Nowson CA, Jarman HF, Malon R, Ackland LM. Eur J Clin Nutr. 2007 Nov 28.

Gruenwald J, Graubaum HJ, Harde A. Adv Ther. 2002 May-Jun;19(3):141-50.

Harris E, Kirk J, Rowsell R, Vitetta L, Sali A, Scholey AB, Pipingas A. Hum Psychopharmacol. 2011 Dec;26(8):560-7.

InterAct Consortium. Diabetes Care. 2011 Sep;34(9):1913-8.

McKay DL, Perrone G, Rasmussen H, Dallal G, Hartman W, Cao G, Prior RL, Roubenoff R, Blumberg JB. J Am Coll Nutr. 2000 Oct;19(5):613-21.

Murphy MM, et al. Journal of the American Dietetic Association 2011:in press.

Nilsen RM, Vollset SE, Rasmussen SA, Ueland PM, Daltveit AK. Am J Epidemiol. 2008 Apr 1;167(7):867-74. Epub 2008 Jan 10.

Nordmann AJ, Suter-Zimmermann K, Bucher HC, et al. Am J Med. 2011 Sep;124(9):841-51.e2.

Ribeiro ML, Arçari DP, Squassoni AC, Pedrazzoli J Jr. Mech Ageing Dev. 2007 Oct;128(10):577-80. Epub 2007 Aug 15.

Sarma KV, Udaykumar P, Balakrishna N, Vijayaraghavan K, Sivakumar B. Nutrition. 2006 Jan;22(1 Suppl):S8-14.

Schlebusch L, Bosch BA, Polglase G, Kleinschmidt I, Pillay BJ, Cassimjee MH. S Afr Med J. 2000 Dec;90(12):1216-23.

Stough C, Scholey A, Lloyd J, Spong J, Myers S, Downey LA. Hum Psychopharmacol. 2011 Oct;26(7):470-6.

Tanvetyanon T, Bepler G. Cancer. 2008 Jul 1;113(1):150-7.

Vazir S, Nagalla B, Thangiah V, Kamasamudram V, Bhattiprolu S. Nutrition. 2006 Jan;22(1 Suppl):S2632.

Wilson RD, et al. J Obstet Gynaecol Can. 2007 Dec;29(12):1003.

The Journal of IHP â&#x20AC;&#x201C; Continuing Education successful completion of the questions at the end of this paper has been approved for continuing education by the bddt-n; 1.0 credit nutritional medicine and by the cnpbc; one ce hour.

Acetyl-L-carnitine for depression and mood disorders A novel therapeutic approach

By Rochelle Fernandes, MSc, ND (cand) Rochelle Fernandes, MSc, ND(cand) RD Research Consult 231 Fort York Blvd, Suite 2607, Toronto, ON M5V 1B2 rd.research.consult@gmail.com

Abstract Depressive disorders affect up to one third of adults, and encompass both psychological as well as physical symptoms, resulting in considerable disability with respect to daily functioning. Major depression is defined by the presence of five of the following symptoms: anhedonia (depressed mood), sleep disturbance, weight changes, psychomotor problems, fatigue, lack of concentration, worthlessness/guilt, and suicidal ideation. Selective serotonin/ norepinephrine reuptake inhibitors constitute the standard firstline conventional therapy. Key natural agents include eicosapentanoic acid, St. Johnâ&#x20AC;&#x2122;s wort, 5-hydroxy-tryptophan (5-HTP), and vitamin B12. Acetyl-L-carnitine (ALC) is a new, emerging agent with a growing body of evidence supporting its use in depression. ALC has been shown to improve cellular energy production in specific areas of the brain, increase brain levels of serotonin and norepinephrine, and may regulate expression of the glutamate receptor, mGlu2.

Clinical studies indicate comparable efficacy for ALC compared to other active therapies including fluoxetine and amisulpride, and better tolerability. This article will review emerging research on the role of ALC in depressive disorders.

April/May 2014 l www.ihpmagazine.com 73

Introduction Depression is a debilitating disorder that causes considerable disruption in an individualâ&#x20AC;&#x2122;s life, work, and health. Depression is most common during the second to third decade of life, with as many as up to 30% of patients confirming symptoms, and is twice as common among women compared to men (Merck 2010).

Additionally, symptoms of mood disorders often overlap, making it difficult to distinguish depression from other mood disorders. Depressive disorders are associated with a host of emotional and physical symptoms that interfere with daily function and contribute to decreased interest in daily activities. The Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV) classifies depressive disorders as follows: major depressive disorder, dysthymia and depressive disorder not otherwise specified and mixed depression/anxiety.

Major depressive disorder is defined by the DSM IV as having five of nine symptoms: depressed mood (anhedonia) for majority of the day every day, for a minimum of two consecutive weeks, and other symptoms including the following: sleep disturbance, weight changes, psychomotor problems, fatigue, lack of concentration, worthlessness/guilt and suicidal ideation (Zimmerman 2006 A,B).

Diagnostics methods and tools The following questionnaires are often utilized to help assess depression: a) The Beck Depression Inventory (BDI) measures the intensity, severity, and depth of depression by asking 21 questions. b) The Hamilton Depression Rating Scale (HDRS) is a checklist given by a health care professional as a scale for evaluating therapeutic outcomes and impact on life. c) The Major Depression Inventory (MDI) is a self-administered assessment for depression that incorporates both the ICD-10 symptoms of depression and the DSM-IV-TR symptoms of major depression. d) The Center for Epidemiologic Studies Depression Screen (CES-D) measures depressive symptoms in the past week. e) The Zung Self-Rating Depression Scale assesses four characteristics of depression: the pervasive effect, the physiologic equivalents, psychomotor activities and more. f) The Inventory of Depressive Symptomatology (IDS) is designed for clinician use, as well as for patient self-administration. g) The Primary Care Evaluation of Mental Disorders (PRIME-MD) is a practitioner administered screening tool for depression. A self-administered version is also available.

Etiology The etiology of depression is explained by a combination of three predominant theories focusing on genetic, environmental, and chemical factors. The genetic theory proposes that depression is more common in those with a first degree relative with the same diagnosis. Interestingly, this theory also proposes that genetic factors may be responsible for coping responses to stressors. The environmental theory proposes that circadian rhythms, situational circumstances and poor coping strategies, among many other external factors can produce a depressive state. Finally, chemical theories of depression suggest that imbalances in neurotransmitters and metabolites result in depression; for instance, low serotonin levels promote low levels of norepinephrine, and other monoamine neurotransmitters, while norepinephrine may be involved in regulating serotonin activity, all impacting mood (Barlow 2005, Linner 2004). Yet other chemical theories propose mitochondrial dysfunction as an underlying factor in depression. This article will focus on the biochemical approach, with a particular view to the role of mitochondrial dysfunction and potential effects of acetyl-L-carnitine (ALC) in improving depression by modifying mitochondrial metabolism.

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Conventional treatment There are several categories of anti-depressant therapy, each targeting different mechanisms of action in depression.

Classes of antidepressant therapy include: a) Selective serotonin reuptake inhibitors (SSRIs): These are usually the initial treatment option as they are thought to have fewer side effects. Some examples are fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft) and citalopram (Celexa). b) Serotonin and norepinephrine reuptake inhibitors (SNRIs): These medications include duloxetine (Cymbalta), venlafaxine (Effexor XR) and Desvenlafaxine (Pristiq). c) Norepinephrine and dopamine reuptake inhibitors (NDRIs): An example is Bupropion (Wellbutrin). d) Atypical antidepressants: Some examples of medications that do not fit into the above classifications but are still considered include trazodone (Oleptro), mirtazapine (Remeron) and vilazodone (Viibryd). e) Tricyclic antidepressants: These are often prescribed if SSRI’s are not effective. f) Monoamine oxidase inhibitors (MAOI’s) are often given as a last resort. Some examples are tranylcypromine (Parnate) and phenelzine (Nardil). These also have serious side effects if combined with tyramine-containing foods or SSRI’s. g) Electroconvulsive therapy (ECT) is utilized for depression when other treatments do not work, and often brings faster symptomatic relief than medications.

It is administered by passing electrical currents through the brain with the aim of altering levels of neurotransmitters that are thought to affect depression. h) Counseling and psychotherapy: Psychotherapy such as cognitive behavioural therapy (CBT) attempts to help identify the causes of depression, target negative behaviour/thought patterns and change them.

Many patients wish to avoid medication due to their numerous side effects. These include sexual dysfunction, digestive abnormalities, weight gain, restlessness, headache, sweating, dry mouth, insomnia, tachycardia and constipation (Mayo Clinic 2012). Additionally, a lack of effective relief motivates other patients to seek other alternatives, including naturopathic therapies.

Mainstays of naturopathic approaches to depression include but are not limited to eicosapentanoic acid, St. John’s wort, 5-hydroxy-tryptophan (5-HTP), passiflora, vitamin D, and vitamin B12. Some of these can be given alone or in conjunction with conventional treatments. Recently, novel treatment options are being examined which have been successful in other brain disorders, such as nucleotides, citicoline, and L-carnitine.

Potential role of L-carnitine L-carnitine is an amino acid derivative that is synthesized from lysine and methionine.

The carnitine pool in humans consists of L-carnitine (LC) (non-esterified) and acetyl L-carnitine (ALC) (esterified). L-carnitine is found in several supplemental forms: L-Carnitine (LC), acetyl-L-carnitine (ALC), L-carnitine L-tartrate (LCLT), and propionyl-L-carnitine bound to glycine (GPLC). L-carnitine and actyl-L-carnitine accumulate in the brain through active transport across the blood brain barrier (Nałecz 2004).

One of the main roles of L-carnitine is facilitating fatty acid oxidation (beta oxidation) and mitochondrial production of ATP; L-carnitine enables the movement of fatty acids from the cytosol into the mitochondria, and the breakdown of fatty acid chains for energy. This biological function includes a process by which carnitine acyl-transferases catalyze the exchange of acyl groups between carnitine and coenzyme A (CoA) (Tong 2004). Other biological functions of LC and ALC include reducing neurological damage by regulating mitochondrial permeability and protecting against excitotoxicity; increasing cellular insulin sensitivity; and improving smooth

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muscle function as in the cardiovascular system (DiNicolantonio 2013, Jones 2010, Vidal-Casariego 2013, Zanelli 2005). These functions render L-carnitine potentially useful in conditions including chronic fatigue syndrome, diabetes, hypertension, congestive heart failure, cancer and metabolic syndrome. ALC is already used to improve cognition in those with Alzheimer’s and dementia, with a large body of evidence on this subject (Montgomery 2003). Interestingly, carnitine is now being considered as a novel therapeutic option for other related neurological conditions, such as depression and other psychiatric diagnoses.

In the body, carnitine maintenance and turnover occurs via dietary intake, synthesis, and reabsorption in the kidneys. Carnitine is absorbed by the jejunum, through a sodium dependent transporter (Gross 1986). The levels of absorption are dependent on the dose and source of carnitine. Between 54 - 87% of carnitine is absorbed from food (mainly active transport and can use passive transport), and 14-18% from supplements (passive transport only-diffusion) (Rebouche 2004). Levels of carnitine are categorized as follows: a) large, slow turnover in muscle; and b) small, rapid turnover (in liver, kidney and other organs. At normal dietary intakes, whole-body turnover in humans is 38-119 hours (Rebouche 2004). Serum L-carnitine levels appears to be regulated in the range of 23–73µmol/L, while acetyl-L-Carnitine appears to be in the range of 3–14µmol/L (Minkler 2008).

The common dosage range of carnitine is between 500 to 2000 milligrams per day and varies depending on the intended use (Malaguarnera 2011).

Mechanisms of action in depression Preclinical studies suggest therapeutic potential for L-carnitine in models of depression, delineating two possible mechanisms: 1) neurochemical and 2) epigenetic.

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Smeland et al investigated the effect of ALC on cerebral ATP levels and neurotransmitter metabolism after supplementing mice with ALC for 25 days, providing a daily dose of about 0.5 g/kg, after which neurometabolites were measured in the hippocampus and cortex. ALC treated mice had higher amounts of adenosine nucleotides, phosphocreatine and ratio of phosphocreatine/creatine in the cerebral cortex. There was decreased glucose conversion to lactate, resulting in increased energy and altered monoamine metabolites.

The study also showed increased concentrations of the neurotransmitters, norepinephrine in the hippocampus and serotonin in the cortex. These biochemical changes suggest that ALC may have an effect on neurochemical modulation in depression (Smeland 2012).

Other studies in rat and mouse models add further confirmation to this concept at the molecular level. One study showed that ALC had an antidepressant function through epigenetic regulation of type 2 metabotropic glutamate (mGlu2) receptors.

Both models showed that ALC increased transcription of the Grm2 gene (encoding for the mGlu2 receptor) in the hippocampus and prefrontal cortex; this was associated with a rapid-onset but long-lasting antidepressant effect observed in rats and mice exposed to chronic unpredictable stress (Nasca 2013).

Cuccurazzu et al. showed similar findings (2013).

Clinical evidence Intriguingly, there is an emerging pool of clinical evidence that supports carnitine as a novel therapeutic option in depression and associated mood disorders. It is thought that bipolar disorder, dysthymia and depression can be attributed in part to chronic mitochondrial dysfunction or imbalances of neurological metabolites (Anglin 2012, Tobe 2013, Torrell 2013). Several studies have attempted to examine this hypothesis by assessing whether patients treated with LC/ALC would experience an improvement in these conditions. Table 1 provides a summary of clinical studies that evaluate the potential benefit of carnitine.

The Journal of IHP – Continuing Education Reference Design Intervention studies Bersani RDBCT; 2013 N=80 patients with dysthymia; ALC 1g 3x/d (treatment), or Brennan 2013

Fluoxetine 20mg (control) RDBPCT;

Outcome After seven weeks, patients receiving ALC showed a statistically significant improvement in the following scales: HAM-D, HAM-A, BDI and Touluse Pieron Test. There was also a notable difference in the latency time of clinical response, with 1 week in the ALC group vs. 2 weeks in the fluoxetine group.

This study examined levels of brain metabolites after ALC administration using proton magnetic resonance spectroscopy.

N=40 patients with bipolar; Overall there was no difference between groups with respect to ALC 1-3g/d in addition to depression severity on the Montgomery-Asberg Depression Rating Scale alpha lipoic acid 600-1800mg/ (MADRS) after 12 weeks. d, compared to placebo x 12wk However, ALC+ALA significantly reduced phosphocreatine levels in the parieto-occipital cortex at week 12 (P = 0.002), and there were decreased whole brain total nucleoside triphosphate levels from baseline to week 1, alongside a decrease in MADRS scores (P = 0.02) in the ALC group.

Marinotti RDBPCT; IV ALC accelerated the improvement of anhedonia, reaching constant 2011 low levels on day 10, whereas the natural course of anhedonia recedes N=64 abstinent anhedonic gradually over 30 days. Anhedonia and melancholic symptoms were alcohol dependent patients; significantly reduced (p<0.05) in both the IV ALC 3g and ALC 1g groups ALC 3g/d; ALC 1g/d; placebo. with respect to placebo; during oral treatment with ALC, however, anhedonia scores did not differ from placebo. Authors concluded ALC was given IV x10d followed by 80d oral treatment that IV ALC was effective in accelerating the abstinence-associated improvement of anhedonia, melancholic and negative symptoms, and 45d follow up period. whereas oral ALC treatment starting on day 10 showed no further improvements.

Malaguarnera RDBPCT; In addition to improvements in urea and bilirubin levels, ALC treated 2011 patients showed improvements in physical function (p<0.001), role N=67 patients with minimal physical (p<0.001), general health (p<0.001), social function (p<0.05), hepatic encephalopathy role emotional (p<0.05), mental health (p<0.05), Beck Depression ALC 2g 2x/d or placebo x90d Inventory (p<0.001).

Zanardi RDBCT Patients diagnosed with pure dysthymia (DSM IV) showed similar 2006 improvements following ALC and amisulpride treatment, as measured by N=204 patients with Hamilton Depression Rating Scale scores (HAM-D) and other measures dysthymia; (no significant differences between groups).

Amisulpride control; Authors noted: “the greater tolerability of ALCAR is of clinical relevance considering the chronicity of dysthymia, which often requires prolonged ALC 500mg 2x/d x 12wk treatment.”

Cavallini RPCT This study compared three groups: testosterone undecanoate versus PLC/ 2004 ALC versus placebo, in the treatment of symptoms related to male aging, N=120 men with depression including fatigue, sexual dysfunction, and depression. Men receiving related to male aging; testosterone or carnitines significantly showed improvements in all three PLC/ ALC 2g/d, or areas, including Depression Melancholia Scale scores, compared to no testosterone, or placebo x6mo effect in the placebo group.

Pettegrew 31P-MRS study N=2 elderly This study investigated the effect of ALC in depression by measuring 2002 depressed subjects compared high-energy phosphate and membrane phospholipid metabolism, and its to six elderly controls; correlation with Hamilton Depression Rating Scale (HDRS) scores in ALC 3g/d x 12wk depressed subjects.

The results showed that initially increased phosphomonesters [PME(s tau(c))] was normalized after ALC treatment.

There was also an increase in phosphocreatine (PCr) levels in the prefrontal cortex, which was associated with better depression scores after 12 weeks of ALC treatment.

Observational studies Rezaee Cross-sectional correlation According to Beck Depression Inventory definitions, at total of 31%, 2013 study; 16%, and 21% of the patients had mild, moderate, and severe depression, respectively. Fifty-four (54%) patients were categorized as carnitine N=100 HIV patients; deficient. A non-statistically significant negative correlation between No intervention patients’ depression scores and total levels of serum carnitine was found.

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Outcome Intervention studies After seven weeks, patients receiving ALC showed a statistically significant improvement in the following scales: HAM-D, HAM-A, BDI and Touluse Pieron Test.

There was also a notable difference in the latency time of clinical response, with 1 week in the ALC group vs. 2 weeks in the fluoxetine group.

This study investigated the effect of ALC in depression by measuring high-energy phosphate and membrane phospholipid metabolism, and its correlation with Hamilton Depression Rating Scale (HDRS) scores in depressed subjects.

The results showed that initially increased phosphomonesters [PME(s - tau(c))] was normalized after ALC treatment.

This study examined levels of brain metabolites after ALC administration using proton magnetic resonance spectroscopy.

There was also an increase in phosphocreatine (PCr) levels in the prefrontal cortex, which was associated with better depression scores after 12 weeks of ALC treatment.

Overall there was no difference between groups with respect to depression severity on the Montgomery-Asberg Depression Rating Scale (MADRS) after 12 weeks.

Observational studies According to Beck Depression Inventory definitions, at total of 31%, 16%, and 21% of the patients had mild, moderate, and severe depression, respectively. Fifty-four (54%) patients were categorized as carnitine deficient. A non-statistically significant negative correlation between patients’ depression scores and total levels of serum carnitine was found.

However, ALC+ALA significantly reduced phosphocreatine levels in the parieto-occipital cortex at week 12 (P = 0.002), and there were decreased whole brain total nucleoside triphosphate levels from baseline to week 1, alongside a decrease in MADRS scores (P = 0.02) in the ALC group.

IV ALC accelerated the improvement of anhedonia, reaching constant low levels on day 10, whereas the natural course of anhedonia recedes gradually over 30 days. Anhedonia and melancholic symptoms were significantly reduced (p<0.05) in both the IV ALC 3g and ALC 1g groups with respect to placebo; during oral treatment with ALC, however, anhedonia scores did not differ from placebo. Authors concluded that IV ALC was effective in accelerating the abstinence-associated improvement of anhedonia, melancholic and negative symptoms, whereas oral ALC treatment starting on day 10 showed no further improvements.

In addition to improvements in urea and bilirubin levels, ALC treated patients showed improvements in physical function (p<0.001), role physical (p<0.001), general health (p<0.001), social function (p<0.05), role emotional (p<0.05), mental health (p<0.05), Beck Depression Inventory (p<0.001).

Patients diagnosed with pure dysthymia (DSM IV) showed similar improvements following ALC and amisulpride treatment, as measured by Hamilton Depression Rating Scale scores (HAM-D) and other measures (no significant differences between groups).

Authors noted: “the greater tolerability of ALCAR is of clinical relevance considering the chronicity of dysthymia, which often requires prolonged treatment.”

This study compared three groups: testosterone undecanoate versus PLC/ALC versus placebo, in the treatment of symptoms related to male aging, including fatigue, sexual dysfunction, and depression. Men receiving testosterone or carnitines significantly showed improvements in all three areas, including Depression Melancholia Scale scores, compared to no effect in the placebo group.

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References Anglin RE, Mazurek MF, Tarnopolsky MA, Rosebush PI. The mitochondrial genome and psychiatric illness. Am J Med Genet B Neuropsychiatr Genet. 2012 Oct;159B(7):749-59.

Barlow, D. Abnormal psychology: An integrative approach (5th ed.). Belmont, CA, USA: Thomas Wadsworth, 2005.

Bella R, Biondi R, Raffaele R, Pennisi G. Effect of acetylL-carnitine on geriatric patients suffering from dysthymic disorders. Int J Clin Pharmacol Res. 1990;10(6):355-60.

Bersani G, Meco G, Denaro A, Liberati D, Colletti C, Nicolai R, Bersani FS, Koverech A. L-acetylcarnitine in dysthymic disorder in elderly patients: a double-blind, multicenter, controlled randomized study vs. fluoxetine. Eur Neuropsychopharmacol. 2013 Oct;23(10):1219-25.

Brennan BP, Jensen JE, Hudson JI, Coit CE, Beaulieu A, Pope HG Jr, Renshaw PF, Cohen BM. A placebo-controlled trial of acetyl-L-carnitine and α-lipoic acid in the treatment of bipolar depression. J Clin Psychopharmacol. 2013 Oct;33(5):627-35.

Cavallini G, Caracciolo S, Vitali G, Modenini F, Biagiotti G. Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Urology. 2004 Apr;63(4):641-6.

Cuccurazzu B, Bortolotto V, Valente MM, Ubezio F, Koverech A, Canonico PL, Grilli M. Upregulation of mGlu2 receptors via NF-κB p65 acetylation is involved in the Proneurogenic and antidepressant effects of acetyl-l-carnitine. Neuropsychopharmacology. 2013 Oct;38(11):2220-30.

DiNicolantonio JJ, Lavie CJ, Fares H, Menezes AR, O’Keefe JH. L-carnitine in the secondary prevention of cardiovascular disease: systematic review and metaanalysis. Mayo Clin Proc. 2013 Jun;88(6):544-51.

The Journal of IHP – Continuing Education Garzya G, Corallo D, Fiore A, Lecciso G, Petrelli G, Zotti C. Evaluation of the effects of L-acetylcarnitine on senile patients suffering from depression. Drugs Exp Clin Res. 1990;16(2):101-6.

Gross CJ, Henderson LM, Savaiano DA. Uptake of L-carnitine, D-carnitine andbacetyl-L-carnitine by isolated guinea-pig enterocytes. Biochim Biophys Acta. 1986bMay 29;886(3):425-33.

Jones LL, McDonald DA, Borum PR. Acylcarnitines: role in brain. Prog Lipid Res. 2010 Jan;49(1):61-75.

Linnér L, Wiker C, Arborelius L, Schalling M, Svensson TH. Selective noradrenaline reuptake inhibition enhances serotonergic neuronal activity and transmitter release in the rat forebrain. J Neural Transm. 2004 Feb;111(2):127-39.

Malaguarnera M, Bella R, Vacante M, Giordano M, Malaguarnera G, Gargante MP, Motta M, Mistretta A, Rampello L, Pennisi G. Acetyl-L-carnitine reduces depression and improves quality of life in patients with minimal hepatic encephalopathy. Scand J Gastroenterol.

2011 Jun;46(6):750-9.

Martinotti G, Andreoli S, Reina D, Di Nicola M, Ortolani I, Tedeschi D, Fanella F, Pozzi G, Iannoni E, D’Iddio S, Prof LJ. Acetyl-l-Carnitine in the treatment of anhedonia, melancholic and negative symptoms in alcohol dependent subjects. Prog Neuropsychopharmacol Biol Psychiatry.

2011 Jun 1;35(4):953-8.

Mayo Clinic. Antidepressants: Get tips to cope with side effects. URL: http://www.mayoclinic.org/diseasesconditions/depression/in-depth/antidepressants/art20049305 Retrieved December 10, 2013.

Merck. The Merck Manual, 2010. Retrieved December 10, 2013 Minkler PE, Stoll MS, Ingalls ST, Yang S, Kerner J, Hoppel CL. Quantification of carnitine and acylcarnitines in biological matrices by HPLC electrospray ionizationmass spectrometry. Clin Chem. 2008 Sep;54(9):1451-62.

Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer’s disease. Int Clin Psychopharmacol. 2003 Mar;18(2):61-71.

Nałecz KA, Miecz D, Berezowski V, Cecchelli R. Carnitine: transport and physiological functions in the brain. Mol Aspects Med. 2004 Oct-Dec;25(5-6):551-67.

Nasca C, Xenos D, Barone Y, Caruso A, Scaccianoce S, Matrisciano F, Battaglia G, Mathé AA, Pittaluga A, Lionetto L, Simmaco M, Nicoletti F. L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4804-9.

Pettegrew JW, Levine J, Gershon S, Stanley JA, ServanSchreiber D, Panchalingam K, McClure RJ. 31P-MRS study of acetyl-L-carnitine treatment in geriatric depression: preliminary results. Bipolar Disord. 2002 Feb;4(1):61-6.

NIH (Ed.), Carnitine; the science behind a conditionally essential nutrient. Bethseda, Maryland: NIH, 2004 Rezaee H, Khalili H, Hatamkhani S, Dashti-Khavidaki S, Khazaeipour Z. Frequency of depression and its correlation with serum carnitine level in HIV/AIDS patients. Curr HIV Res. 2013 Apr;11(3):226-30.

Rossini M, Di Munno O, Valentini G, Bianchi G, Biasi G, Cacace E, Malesci D, La Montagna G, Viapiana O, Adami S. Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients. Clin Exp Rheumatol. 2007 Mar-Apr;25(2):182-8.

Smeland OB, Meisingset TW, Borges K, Sonnewald U. Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. Neurochem Int. 2012 Jul;61(1):100-7.

Tempesta E, Casella L, Pirrongelli C, Janiri L, Calvani M, Ancona L. L-acetylcarnitine in depressed elderly subjects.

A cross-over study vs placebo. Drugs Exp Clin Res. 1987;13(7):417-23.

Tobe EH. Mitochondrial dysfunction, oxidative stress, and major depressive disorder. Neuropsychiatr Dis Treat.

2013;9:567-73.

Tong, L. Structure and function of carnitine acyltransferases. In NIH (Ed.), CARNITINE: THE SCIENCE BEHIND A CONDITIONALLY ESSENTIAL NUTRIENT. Bethseda, Maryland: NIH, 2004.

Torrell H, Montaña E, Abasolo N, Roig B, Gaviria AM, Vilella E, Martorell L. Mitochondrial DNA (mtDNA) in brain samples from patients with major psychiatric disorders: gene expression profiles, mtDNA content and presence of the mtDNA common deleteon. Am J Med Genet B Neuropsychiatr Genet. 2013 Mar;162B(2):213-23.

Vidal-Casariego A, Burgos-Peláez R, Martínez-Faedo C, Calvo-Gracia F, Valero-Zanuy MÁ, Luengo-Pérez LM, Cuerda-Compés C. Metabolic effects of L-carnitine on type 2 diabetes mellitus: systematic review and meta-analysis.

Exp Clin Endocrinol Diabetes. 2013 Apr;121(4):234-8.

Zanardi R, Smeraldi E. A double-blind, randomised, controlled clinical trial of acetyl-L-carnitine vs. amisulpride in the treatment of dysthymia. Eur Neuropsychopharmacol.

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Zanelli SA, Solenski NJ, Rosenthal RE, Fiskum G. Mechanisms of ischemic neuroprotection by acetyl-Lcarnitine. Ann N Y Acad Sci. 2005 Aug;1053:153-61.

Zimmerman M, McGlinchey JB, Chelminski I, Young D. Diagnosing major depressive disorder V: applying the DSM-IV exclusion criteria in clinical practice. J Nerv Ment Dis. 2006 Jul;194(7):530-3. A Zimmerman M, McGlinchey JB, Young D, Chelminski I. Diagnosing major depressive disorder introduction: an examination of the DSM-IV diagnostic criteria. J Nerv

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Rebouche, C. Kinetics, pharmacokinetics and regulation of L-Carnitine and Acetyl L Carnitine Metabolism. In April/May 2014 l www.ihpmagazine.com 79

Questions 1. According to the DSM-IV, major depression is characterized by five of nine symptoms. These include the existence of anhedonia for a minimum of two weeks in combination with which of the following symptoms? a) delusions of grandeur b) insomnia c) anxiety b) all of the above 2. V alidated questionnaires are used to assess depression severity. These include which of the following? a) Beck Depression Inventory b) Visual Analog Scale c) Hamilton Depression Rating Scale d) A and C 3. Bupropion (Wellbutrin) is a norepinephrine and dopamine reuptake inhibitor (NDRI). a) True b) False 4. Which of the following is NOT true? a) Venlafaxine (Effexor) is a serotonin and norepinephrine reuptake inhibitor (SNRI) b) Citalopram (Celexa) is a selective serotonin reuptake inhibitor (SSRI) c) D uloxetine (Cymbalta) is a selective serotonin reuptake inhibitor (SSRI) d) Trazadone is atypical antidepressant 5. Mitochondrial dysfunction has been proposed as a potential causative factor in the etiology of depression. Acetyl-L-carnitine may improve mitochondrial function through which of the following mechanisms? a) L -carnitine enables the movement of fatty acids from the cytosol into the mitochondria b) Carnitine acyl-transferases catalyze the exchange of acyl groups between carnitine and coenzyme A (CoA) c) L -carnitine regulates mitochondrial permeability and protects against excitotoxicity d) all of the above

6. Supplementation of acetyl-L-carnitine in animal models resulted in important changes in brain biochemistry, including higher levels of lactate and creatine to phosphocreatine in the cerebral cortex. a) True b) False 7. Supplementation of acetyl-L-carnitine has also been shown to achieve which of the following in animal models of depression? a) ALC increased transcription of serotonin receptors in the cerebral cortex b) ALC regulated transcription of metabotropic glutamate (mGlu2) receptors in the hippocampus c) ALC decreased expression of NF-kappa B in the prefrontal cortex d) all of the above 8. Clinical trials show that supplementation with acetyl-L-carnitine increased brain levels of phosphomonoesters and phosphocreatine in elderly depressed patients as demonstrated by magnetic resonance spectroscopy. a) True b) False 9. In patients with dysthymia, supplementation with acetyl-L-carnitine resulted in significant improvements in which of the following endpoints? a) Hamilton depression rating scale b) Hamilton anxiety rating scale c) Beck depression inventory d) all of the above 10. In abstinent, alcohol dependent patients with anhedonia, intravenous administration of acetylL-carnitine resulted in accelerated improvement of abstinence-related symptoms, reducing this time period from 30 days to 10 days. a) True b) False

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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 fatigue associated with exercise (Howatson 2012, Shimomura 2010). the 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 freeto mass especially in conjunction with resistance training (Cooper Creatine acts as a primarily due to extensive lesion of the plasma membrane (Salgueiro 2003). phosphorus donor in the regeneration of ATP from ADP via the ATP- phosphocreatine energy system, a crucial anaerobic energy source during high intensity (Cooperseveral 2012). In addition, a species, recent study demonstrated creatine’s abilityaureus, to reduceBacillus markers of muscle activity as well ashas in between of high intensity activity 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.

2012). addition, glutamine may help offset loss of lean muscle mass of during acute illness: to prevent overtraining inducedintegrity immune suppression 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.

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 Table 1. activrecover+ and Vegan activrecover+ formula, per 40g (1 scoop) relative safety of Oregano oil.

Action Ingredient Dose Carvacrol was shown to be hepatoprotective against ischemia and reperfusion injury in rats; both carvacrol and silymarin Rebuild Whey protein isolate (bovine milk) 6.6g had similar beneficial effectspea onprotein AST isolate and ALT levels (Canbek 2007). Carvacrol also increased liver regeneration rate in rats Pisum sativum: Yellow activrecover+ after partial hepatectomy (Uyanoglu 2008).

Pisumstudies sativum: of Yellow pea protein isolate Mutagenicity carvacrol show only weak activity; carvacrol is excreted in urine after 24 hours in large quantities, Solanum tuberosum: Potato tuber protein isolate Vegan unchanged or as glucoronide and sulphate conjugates (De Vincenzi 2004). activrecover+ Pisumsativum: yellow pea protein isolate

5.7g 2.0g L-leucine Canbek M, Uyanoglu M, Bayramoglu G, Senturk H, Erkasap1.0g N, Koken T, Uslu S, Demirustu C, Aral E, Husnu Can Baser 500mg Effects ofL-isoleucine carvacrol on defects of ischemia-reperfusion in the rat liver. Phytomedicine. 2008 Jan. L-valine 500mg Fitoterapia 2004; 75(7-8): 801-804.

De Vincenzia M et al. Constituents of aromatic plants: carvacrol.

L-glutamine 500mg Force M Zea et al.

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

Re-Energize mays fruit: D-glucose 9.5g

References Creatine monohydrate

K.

Lambert Oryza RJ, Skandamis PN, Coote PJ, Nychas GJ. A study of7.9g the minimum inhibitory concentration and mode of action of sativa: whole grain sprouted brown rice dry syrup oregano essential oil, thymol and carvacrol.

J Appl Microbiol.

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

Citrus sinensis: sweet orange fruit powder 4.0g Nostro A,Aloysiacitrodora: Roccaro AS, Bisignano G,leaf Marino A, Cannatelli MA, Pizzimenti FC, Cioni PL, Procopio F, Blanco AR. Effects of Restore lemon verbena 600mg oregano, Prunuscerasus: carvacrol andtartthymol on Staphylococcus aureus and Staphylococcus epidermidis biofilms. J Med Microbiol. cherry fruit skin 100mg 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.

References May 7;7:17. et al. J IntSocSports Nutr. 2010 Salgueiro LR et al. Chemical composition and antifungal activity Kuehl of theKS, essential oil of Origanum virens on Candida species.

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.

NEM® SAP

PRODUCT MONOGRAPH Natural eggshell membrane (NEM®) is a natural-sourced supplement that is derived from hen eggshell membrane.

It contains naturally occurring glycosaminoglycans (GAGs), glucosamine, chondroitin, hyaluronic acid, and proteins, that are useful for maintaining healthy articular cartilage and surrounding synovium and connective tissue.[1, 3] NEM® is a viable safe alternative treatment of pain and stiffness associated with osteoarthritis or joint degeneration. NEM® SAP contains both NEM® and Boswellia serrata to maximize the anti-inflammatory properties of this product and to provide maximum benefit to patients.

NEM® FOR JOINT AND CONNECTIVE TISSUE DISORDERS

In two open-label human clinical trials, patients with a variety of joint and connective tissue disorders, including knees, hips, shoulders, elbows, neck, or back, were given 500 mg NEM® for one month.[1] Patients were assessed for either general pain (both studies) or range of motion and general pain (one study) at 7 days and 30 days.[1] These studies found that 33% of patients experienced >30% pain reduction at 7 days and 66% of patients experienced a >50% reduction in pain at 30 days.[1] Both these studies had a small number of participants and tested a variety of different joint pathologies, which may explain some of the variation in study outcomes.

In a double-blind, placebo-controlled study, 67 participants with osteoarthritis of knee received either 500 mg NEM® or placebo for 8 weeks.[3] Participants were evaluated based on the Western Ontario and MacMaster (WOMAC) osteoarthritis scale, as well as pain, stiffness, and functional WOMAC subscales, at days 10, 30 and 60.[3] At 10 days, there was an average reduction in pain of 15.9% and an average improvement of stiffness of 12.8%. By day 60, there was an absolute rate of response that was found to be statistically significant of 26.6% in both pain and stiffness.[3] Researchers concluded that NEM® is safe and effective for treating pain and stiffness associated with osteoarthritis of the knee.[3]

NEM® INFLAMMATORY PROPERTIES

In a study exploring the potential mechanism of action of NEM®, researchers exposed human immune cells to different mitogens known to elicit an inflammatory response.[4] Cells pre-treated with a water extract of NEM® were found to significantly reduce serum For more information visit: www.nfh.ca

IHP 2014-04,05 (NEM® SAP).indd 2

TNF-alpha after exposure to phytohemagglutinin (PHA).[6] Researchers in this study also looked at the effect of human digestion on NEM® efficacy. NEM® was exposed to a pre-treatment that simulated gastrointestinal digestion, and then used to treat the immune cells prior to exposure to pokeweed mitogen (PWM). PWM is a mitogen which induces a more extensive immune response than PHA by including T cells, B cells, and monocytes.[4] The serum level of TNF-alpha was significantly reduced with pre-treated NEM® compared to when cells were exposed to PWM alone. These results indicate that NEM® does not appear to be negatively impacted by digestive enzymes, and that NEM® appears to have a positive effect on immunomodulation.[4]

BOSWELLIA (Boswellia serrata)

Boswellia (Boswellia serrata) has been used historically in Ayurvedic medicine for the treatment of chronic inflammatory conditions.[5, 6] The resinous part of boswellia contains monoterpenes, diterpenes, triterpenes, tetracyclic triterpenic acids, and four major pentacyclic triterpenic acids.[6] 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-lipoxygenase (LOX), an enzyme responsible for inflammation.[5, 6] Historically, the common preparations of boswellia may contain minimal or varying boswellic acid content. NEM® SAP contains boswellia extract standardized to 70% boswellic acids.

REFERENCES 1.

2.

3.

4.

5.

6.

Ruff, K.J., et al. “Eggshell membrane: a possible new natural therapeutic for joint and connective tissue disorders. Results from two open-label human clinical studies”. Clinical Interventions in Aging Vol. 4 (2009): 235–240.

Ruff, K.J., et al. “Safety evaluation of a natural eggshell membrane-derived product”. Food and Chemical Toxicology Vol. 50, No. 3–4 (2012): 604–611.

Ruff, K.J., et al. “Eggshell membrane in the treatment of pain and stiffness from osteoarthritis of the knee: A randomized multicenter, double-blind, placebo-controlled clinical study”. Clinical Rheumatology Vol. 28, No. 8 (2009): 907–914.

Benson, K.F., K.F. Ruff, and G.S. Jensen. “Effects of natural eggshell membrane (NEM) on cytokine production in cultures of peripheral blood mononuclear cells: Increased suppression of TNF-alpha levels after in vitro digestion”.

Journal of Medicinal Food Vol. 15, No. 4 (2012): 360–368.

Wallace, J.M. “Nutiritional and botanical modulation of the inflammatory cascade—eicosanoids, cyclooxygenases, and lipoxygenases—as an adjunct in cancer therapy”. Integrative Cancer Therapies Vol. 1, No. 1 (2002): 7–37.

Siddiqui, M.Z. “Boswellia serrata, a potential antiinflammatory agent: an overview”. Indian Journal of Pharmaceutical Sciences Vol. 73, No. 3 (2011): 255–261.

NEM® is a registered trademark of ESM Technologies, LLC.

© NFH Nutritional Fundamentals for Health 2014

2014-04-01 16:41:39

NEM® SAP Science-based joint support

Natural eggshell membrane (NEM®) is the thin membrane that forms the inner lining of hen eggshells. It contains many ingredients that are known to help support joint health, including collagen, glucosamine, hyaluronic acid, glycosaminoglycans (GAGs), and chondroitin sulfate, as well as several other proteins and peptides.[1] Studies have demonstrated that NEM® can improve symptoms of pain and stiffness associated with osteoarthritis within 7–10 days of starting supplementation.[1] NEM® SAP combines NEM® with the botanical Boswellia serrata (frankincense) to optimize its positive effects on reducing pain and inflammation. NEM® SAP provides a safe and effective treatment for pain and stiffness associated with osteoarthritis as well as other inflammatory processes.

Each capsule of NEM® SAP contains:

ACTIVE INGREDIENTS

Partially hydrolyzed chicken eggshell membrane (NEM®) . . . . . . . . . . . . . . . . . . . . 500 mg Boswellia serrata (70% boswellic acids) . . . . . . . . . . . 135 mg NEM® SAP contains 30 capsules per bottle Contains no: Preservatives, artificial flavor or color, sugar, dairy, starch, wheat, gluten, yeast, citrus, or corn

ADULT DOSAGE

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

Consult a health care practitioner for use beyond 8 weeks.

INDICATIONS

ɶ NEM® SAP may help relieve joint pain associated with osteoarthritis. ɶ NEM® SAP may assist in improving stiffness and range of motion in joints. ɶ NEM® SAP may help reduce TNF‑alpha production, supporting a healthy inflammatory response.

SAFETY

NEM® has generally recognized as safe (GRAS) status and has been demonstrated to be safe at up to 50 times the human dose of 500 mg/d.[2] No adverse reactions have been reported.[1] No known interactions with other supplements or pharmaceuticals.

PURITY, CLEANLINESS AND STABILITY

Third‑party testing is performed on the finished product to ensure that NEM® SAP meets the potency claim and is free of heavy metals, pesticides, volatile organics, and other impurities.

NEM® is a registered trademark of ESM Technologies, LLC.

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

Nutritional Fundamentals for Health • 3405 F.-X.-Tessier, Vaudreuil, QC J7V 5V5 • Tel. 1 866 510 3123 • Fax. 1 866 510 3130 • www.nfh.ca

IHP 2014-04,05 (NEM® SAP).indd 1

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