IHP February/March 2014 by Rive Gauche Media

IHP FEBRUARY/MARCH 2014 | $14.95 PM42684014 | 60 BLOOR STREET WEST SUITE 1106 | TORONTO ONTARIO, M4W 3B8

Neurodegeneration

Hypertension

Bioidentical Hormone Therapy

By Eric Muradov, ND

By Elaine Lewis, ND

By Tannaz Mokhtari, ND & Ishita Patel, Pharm D

Integrated Healthcare

Practitioners

Dr Julia Cataudella, MD FertilityCare Toronto

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Continuing Education

Mistletoe Therapy for Cancer Management By Sarah Vanderheyden, RPN & Heidi Fritz, MA, ND

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HLC IMMUNITY + PRO Vitamin C and probiotic formula with clinically proven results

N EW

Help maintain immune function with 1000 mg of vitamin C and 2 billion CFU of probiotics in a great-tasting natural orange-flavoured powder. The dairy-free, gluten-free, vegetarian formula comes in 30 convenient individualized sachets that easily mix into water.

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A Trusted Seroyal Brand

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HLC IMMUNITY + PRO PRODUCT MONOGRAPH

HLC Immunity + Pro is a maintenance probiotic supplement with 1000 mg of vitamin C in a great-tasting orangeflavoured powder. A factor in the maintenance of good health, the dairy-free, gluten-free, soy-free, vegan formula comes in 30 convenient individualized sachets that easily mix into water or as a complementary addition to juice. Vitamin C: There is convincing evidence that megadoses of Vitamin C helps prevent and relieve cold and flu symptoms. A study observed a student test group treated with hourly doses of 1000 mg of Vitamin C for the first 6 hours and then 3 times daily thereafter compared with a control group treated with pain relievers and decongestants. The student test group showed an 85% decrease in overall reported flu and cold symptoms after the administration of megadose vitamin C. Therefore, Vitamin C administered in megadoses before or after the appearance of cold and flu symptoms relieved and prevented the symptoms in the test population compared with the control group.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 HLC Immunity + Pro contains 2 billion CFU per capsule derived from proprietary, human-sourced HLC strains.

Recommended intake Adults: In a glass, add water to one sachet of powder and mix. One sachet taken daily with a meal, a few hours before or after taking other medications, or as professionally directed.

EACH SACHET (8.42 g) CONTAINS: Vitamin C (ascorbic acid) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1000 Thiamine (thiamine hydrochloride) . . . . . . . . . . . . . . . . . . . . . .0.38 Riboflavin (riboflavin-5-phosphate sodium) . . . . . . . . . . . . . 0.43 Niacinamide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Vitamin B6 (pyridoxine hydrochloride) . . . . . . . . . . . . . . . . . . . . .10 Folate (folic acid) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.5 Vitamin B12 (cyanocobalamin) . . . . . . . . . . . . . . . . . . . . . . . . . . . .25 Pantothenic acid (calcium d-pantothenate) . . . . . . . . . . . . . . 2.5 Calcium (calcium carbonate/ calcium phosphate tribasic) . . . . . . . . . . . . . . . . . . . . . . . . . . . . .50 Phosphorus (calcium phosphate tribasic). . . . . . . . . . . . . . . . .13 Magnesium (magnesium hydroxide / carbonate). . . . . . . . .60 Zinc (zinc ascorbate) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Manganese (manganese gluconate) . . . . . . . . . . . . . . . . . . . . 0.5 Chromium [chromium (III) polynicotinate] . . . . . . . . . . . . . . . . .10 Potassium (potassium bicarbonate / carbonate) . . . . . . . 100 HLC Consortium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 billion Lactobacillus acidophilus (CUL-60) Lactobacillus acidophilus (CUL-21) Bifidobacterium animalis subsp. lactis (CUL-34) Bifidobacterium bifidum (CUL-20)

mg mg mg mg mg mcg mcg mg mg mg mg mg mg mcg mg CFU

Non-Medicinal Ingredients: D-fructose, citric acid, DL-malic acid, natural orange flavour, sodium bicarbonate, orange juice powder, maltodextrin (potato), silica, L-tartaric acid, glycine, annatto extract, beta-carotene

1. Gorton HC, Jarvis K. The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections. J Manipulative Physiol Ther. 1999 Oct;22(8):530-3. 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, Oâ&#x20AC;&#x2122;Keefe SJ. Microbial induction of immunity, inflammation, and cancer. Front Physiol. 2011 Jan 26;1:168.

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

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from the publisher Connect With Us

Happy New Year!

hat an exciting winter it has been… Haven’t seen this much snow in many years, yet it’s what winter is all about! It’s also helped deliver some incredible outdoor hockey rinks… Hoping everyone has gotten a chance to get on some skates this year! The IHP website has been fully revamped and is awaiting your visits! Readers have been asking us for a way to access the archive of articles and stories we have published, and we are proud to say they have now been made available. The near future will see us take on the challenge of social media, which we are eager to get up and running. As convenient, informative, and easy to use as social media can be, a dark side to the 21st century darling is beginning to emerge. Recently, a relatively unqualified individual used social media to slam a very reputable supplier… Almost immediately people were returning product and abandoning the company based on what they read, with the company not having a chance to explain themselves! It’s incredible how quickly something can spread through social media, yet also alarming at the same time. The concept of quality control in the natural health products industry is an area I hope IHP can deliver some accurate and important information on as we move through 2014… Looking forward to another good year!

Sanjiv Jagota Publisher

4 www.ihpmagazine.com l February/March 2014

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Products Professionals Prefer®

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Healing Creams & Salves Red Clover Plus Salve, Calendula Vitamin E Cream & Zinc-Chamomile Cream

Product Monograph for IHP, February-March 2014 By Terry Vanderheyden, ND

Red Clover Plus Salve: Premier Anti-Inflammatory for Eczema and Psoriasis, not to mention Anti-microbial and First-Aid Salve Red Clover Plus Salve is St. Francis Herb Farm’s answer to cortisone for inflammatory conditions of the skin, including eczema and psoriasis. Its antimicrobial properties also make it excellent as a first-aid salve for wounds. Lisa Morgan, owner of Serenity On The Humber Holistic Spa and Natural Product Store, writes the following in a blog post: “I’ve had three clients using this treatment [for eczema] and all have reported back that it has virtually made it disappear. Now they are telling two friends and so on and so on. It’s that simple. They say that it makes a huge difference in even a day. If consistent in using it, it disappears and heals back to almost ‘normal’ skin.” (Morgan 2014) Lisa had a client post their results on the use of the Salve on her Facebook page: “Lisa, I want to thank you so much for telling me about the St. Francis Herb Farm Red Clover Salve for my eczema…I started using it yesterday and could not believe the results overnight with one application!! I’ve been trying to combat it for years … but never seen results like this... I’m almost doing a happy dance lol!”

Calendula Vitamin E Cream: Anti-inflammatory, Wound Healer, and Scar Preventer Calendula is a potent anti-inflammatory and our best wound healer (Yarnell 2004). It is this one-two action that sets calendula apart from other dermatological agents. Its woundhealing and inflammation-dampening properties make it ideal for healing the skin, as the following testimonial strikingly illustrates: “In the year 2010, I was diagnosed with colon cancer. Since then I have had two major surgeries and have undergone chemo and radiation therapy. The side effects from the radiation have been horrendously painful. There is no word to describe it! For the past fifteen months I have used prescription cortisone creams and over the counter creams, but for the most part my condition remained the same. When I started using the St. Francis Herb Farm Calendula Vitamin E Cream, the results were almost immediate. After the first five days of use, I have been having very good relief and comfort all the time. Thank you very, very much for your help. It’s been life-changing. I deeply appreciate it.” S.Halabi, Toronto

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 6 children.

References: Lisa Morgan, http:// serenityonthehumber. wordpress.com/2013/04/23/518/ accessed January 9, 2014. Eric Yarnell, “Compendium of Pharmacological Actions of Medicinal Plants and Their Constituents”, © 2004 Eric Yarnell, ND, RH. Matthew Wood, The Book of Herbal Wisdom, Berkeley, CA: North Atlantic Books; 1997.

The use of calendula immediately after an injury prevents the formation of “unsightly scar tissue” (Wood 1997).

Zinc-Chamomile Cream: Diaper Dermatitis, Rosacea Chamomile is a potent anti-inflammatory agent. The inclusion of zinc, with its moisturebarrier properties, makes this product especially useful for diaper dermatitis, its effectiveness often making itself apparent in a single application! One happy user has written to us saying, “I have been using your Zinc Chamomile Cream on my 15 month old daughter since she was born. She has had multiple diaper rashes, and, by using this cream, I have cleared up the rash every time within 24 hours. It has never caused her any discomfort and smells wonderful. Thanks again for your wonderful products!” Another user relates that, “After having tried many creams and lotions for chronic dermatitis (of the face), Zinc-Chamomile Cream is the only one that has consistently relieved the burning and itching.”

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Products Professionals Prefer® Contact us today to place an order. Call: 1.866.562.9131 Fax: 1.866.353.0427 info@stfrancisherbfarm.com www.stfrancisherbfarm.com

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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 Art Director | Rico Marques Production Manager | Erin Booth (416) 203-7900 ext. 6110 Production Design Intern Tamara Kelly

Contributors Christopher Habib, ND, Philip Rouchotas, MSc, 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

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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 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.

Truly a benefit for your patients!

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

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

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contents

This Issue: February/March 2014 • Vol. 7 • No. 1

30 FertilityCare Toronto Cover Story

A Restorative Approach To Women’s Health

38 Tapout Training Center Clinic Profile

Peak Performance Care For Elite Athletes

42 The Journal of IHP

Peer-reviewed articles on clinically revelant topics

Coming Next Issue • L-Carnitine and Depression • Cortisol and Mental Health • NEM- Literature Review Cover Photograph by Bruce Redstone

8 www.ihpmagazine.com l February / March 2014

Departments

4 Publisher’s Letter 11 Research News 19 Industry News 24 Calendar 25 Product Profiles 43 Editor’s Letter 45 Peer Review Board 47 Editorial Board 73 Continuing Education: Improving Outcomes In Complementary Cancer Care By Sara Vanderheyden, RPN and Heidi Fritz, MA, ND

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.

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RevitalAge Ultra ™

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

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

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

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

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

v 00

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

3 capsules daily, with meals. †Under

license from

Inc.

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

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

IHPAPR2012_XXXX_ADVERTISER_Product_FP.indd 4

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research news Antiviral treatment for Hep C improves renal and cardiovascular outcomes in diabetics This population-based cohort study aimed to investigate whether antiviral therapy for Hepatitics C Virus (HCV) infection was associated with clinical outcomes in diabetes. From the Taiwan National Health Insurance Research Database, 2,267,270 Taiwanese residents diagnosed with diabetes mellitus were screened for eligibility. After excluding patients with serious comorbidity, they enrolled a total of

1,411 eligible patients who received pegylated interferon plus ribavirin (treated cohort), and matched them 1:1 with 1,411 untreated controls by propensity scores (untreated cohort). Participants were followed up for the occurrence of end-stage renal disease (ESRD), ischemic stroke, and acute coronary syndrome (ACS) after receiving antiviral treatment or the corresponding calendar date. The results showed that from 2003 to 2011, the 8-year cumulative incidences of ESRD in the treated, untreated, and uninfected cohorts were 1.1%, 9.3%, and 3.3% respectively; those of stroke were 3.1%, 5.3%, and 6.1%, respectively; and those for ACS were 4.1%, 6.6%, and 7.4%, respectively. As compared with the untreated cohort, antiviral treatment was associated with multivariate-adjusted hazard ratios of 0.16 for ESRD, 0.53 for ischemic stroke, and 0.64 for ACS, respectively. The authors conclude antiviral therapy for HCV improves clinical outcomes in diabetes. Hepatology, October 2013.

Vitamin D may help with Multiple Sclerosis Multiple Sclerosis (MS) is associated with vitamin D deficiency. This study examined some of the immunological effects of vitamin D on the prevention of MS in a mouse model. Pharmacologic targeting of T helper (TH) cell trafficking poses an attractive opportunity for amelioration of autoimmune diseases. The bioactive form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], has been shown to prevent experimental autoimmune encephalomyelitis, a mouse model of MS, via an incompletely understood mechanism. In this study, the authors systematically examined 1,25(OH)2D3 effects on TH cells during their migration from the lymph nodes to the CNS. The results showed that myelin-reactive TH cells are successfully generated in the presence of 1,25(OH)2D3, secrete proinflammatory cytokines, and do not preferentially differentiate into suppressor T cells. These cells are able to leave the lymph node, enter the peripheral circulation, and migrate to the s.c. immunization sites. However, TH cells from 1,25(OH)2D3-treated mice are unable to enter the CNS parenchyma but are instead maintained in the periphery. Upon treatment cessation, mice rapidly develop experimental autoimmune encephalomyelitis, demonstrating that 1,25(OH)2D3 prevents the disease only temporarily likely by halting TH cell migration into the CNS. Proc Natl Acad Sci U S A, December 2013. PMID: 24324134

Low B12 predicts incident fractures in elderly men This population-based study examined cobalamin status and incident fractures in elderly men (n = 790) with an average follow-up of 5.9 years. This study aimed to determine whether serum cobalamins or holotranscobalamin (holoTC: the metabolic active cobalamin) predict incident fractures. Men participating in the Gothenburg part of the population-based Osteoporotic Fracturs in Men (MrOS) Sweden cohort and without ongoing vitamin B medication were included in the study (age range 7081 years). The results showed that 110 men sustained X-ray verified fractures including 45 men with clinical vertebral fractures. The risk of fracture (adjusted for age, smoking, BMI, BMD, falls, prevalent fracture, tHcy, cystatin C, 25-OH-vitamin D, intake of calcium, and physical activity, increased per each standard deviation decrease in cobalamins (HR 1.38; 95 % CI, 1.11-1.72) and holoTC (HR, 1.26; 95 % CI, 1.03-1.54), respectively. Men in the lowest quartile of cobalamins and holoTC had an increased risk of all fracture (cobalamins, HR = 1.67 (95 % CI, 1.06-2.62); holoTC, HR = 1.74 (95 % CI, 1.12-2.69)). No associations between folate or tHcy and incident fractures were seen. The authors conclude that low levels of holoTC and cobalamins predict incident fracture in elderly men. Osteoporos Int, October 2013. PMID: 24129588

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research news Healthy lifestyles reduce chronic diseases and dementia This cohort study followed 2235 healthy men aged 45-59 starting in 1979, in Caerphilly, UK. During the following 30 years, incident diabetes, vascular disease, cancer, and death were recorded, and cognitive state was determined. The results showed that men who followed four or five of the healthy lifestyle behaviours (non-smoking, an acceptable BMI, a high fruit and vegetable intake, regular physical activity, and low/moderate alcohol intake) had an odds ratio (OR) and confidence intervals (CI) for diabetes, corrected for age and social class, of 0.50. For vascular disease the OR was 0.50, and there was a delay in vascular disease events of up to 12 years. Cancer incidence was not significantly related to lifestyle although there was a reduction associated with non-smoking (OR: 0.65). All cause mortality was reduced in men following four or five behaviours (OR 0.40). The OR for men following four or five healthy behaviours was 0.36 for cognitive impairment, and 0.36 for dementia. The adoption of a healthy lifestyle by men was low and appears not to have changed during the subsequent 30 years. The authors conclude that a healthy lifestyle is associated with increased disease-free survival and reduced cognitive impairment. PLoS One, December 2013. DOI: 10.1371/journal.pone.0081877

An overview of Sucralose as a synthetic organocholorine sweetener This review discusses sucralose, a synthetic organochlorine sweetener (OC) that is a common ingredient in the food supply. Sucralose interacts with chemosensors in the alimentary tract that play a role in sweet taste sensation and hormone

secretion. In rats, sucralose ingestion was shown to increase the expression of the efflux transporter P-glycoprotein (P-gp) and two cytochrome P-450 (CYP) isozymes in the intestine. P-gp and CYP are key components of the presystemic detoxification system involved in first-pass drug metabolism. The effect of sucralose on first-pass drug metabolism in humans is unknown. In rats, sucralose alters the microbial composition in the gastrointestinal tract (GIT), with relatively greater reduction in beneficial bacteria. The identity and safety profile of these putative sucralose metabolites are not known at this time. Sucralose and one of its hydrolysis products were found to be mutagenic at elevated concentrations in several testing methods. Cooking with sucralose at high temperatures was reported to generate chloropropanols, a potentially toxic class of compounds. Both human and rodent studies demonstrated that sucralose may alter glucose, insulin, and glucagon-like peptide 1 (GLP-1) levels. Taken together, these findings indicate that sucralose is not biologically inert. J Toxicol Environ Health B Crit Rev. 2013. PMID: 24219506

A survey of Phthalates and Parabens in Personal Care Products and its implications In this study, nine phthalates and six parabens were determined in 170 personal care products (PCPs) (41 rinse-off and 109 leave-on), including 20 baby care products collected from Albany, New York. The results showed that phthalates were less frequently found in rinse-off PCPs but were more frequently found in perfumes (detection frequency of 100% for diethyl phthalate [DEP], 67% for dibutyl phthalate [DBP]), skin toners (90% for DEP), and nail polishes (90% for DBP). Parabens were found in > 40% of rinse-off products and > 60% of leave-on products. The highest concentrations of DEP, DBP, methyl- (MeP), ethyl- (EtP), propyl- (PrP), and butyl parabens (BuP) were on the order of 1000 Îźg per gram of the product. The calculated dermal intake of phthalates from PCPs was lower for infants and toddlers than for adult females. The calculated maximum daily exposure dose of MeP, EtP, and PrP from PCPs ranged between 58.6 and 766 Îźg/kg-bw/day for infants and toddlers, which was 3 times higher than that calculated for adult females. PCPs are an important source of human exposure to parabens; the contribution of PCPs to phthalate exposure is low, except for DEP. Environ Sci Technol, November 2013. PMID: 24261694

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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)).

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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 Effect of CPAP on blood pressure for sleep apnea This open-label, randomized, multicenter clinical trial of parallel groups used blinded endpoint design, and was conducted in 24 teaching hospitals in Spain involving 194 patients with resistant hypertension and an apnea-hypopnea index (AHI) of 15 or higher. The interventions were CPAP or no therapy while maintaining usual blood pressure control

medication. The primary end point was the change in 24-hour mean blood pressure after 12 weeks. The results showed that 194 patients were randomly assigned to receive CPAP or no CPAP. When the changes in blood pressure over the study period were compared between groups, the CPAP group achieved a greater decrease in 24-hour mean blood pressure (3.1 mm Hg) and 24-hour DBP (3.2 mm Hg), but not in 24-hour SBP compared with the control group. Moreover, the percentage of patients displaying a nocturnal blood pressure dipper pattern at the 12-week follow-up was greater in the CPAP group than in the control group (35.9% vs 21.6%; adjusted odds ratio [OR], 2.4). There was a significant positive correlation between hours of CPAP use and the decrease in 24-hour mean blood pressure (r = 0.29, P = .006), SBP (r = 0.25; P = .02), and DBP (r = 0.30, P = .005). JAMA, December 2013. PMID: 24327037

Effects of coffee, smoking, and hormones on primary sclerosing cholangitis In this study, a questionnaire was distributed to hospital-recruited patients with primary sclerosing cholangitis (PSC). The results showed that a lower proportion of patients with PSC were daily coffee drinkers than control subjects, both currently (76% vs 86%; odds ratio [OR], 0.52) and at the age of 18 years (35% vs 49%; OR, 0.58). The associations were mainly attributed to differences observed in men. Twenty percent of the patients were ever (current or former) daily

Impact of gender on the heart’s metabolic responses to diabetic therapies This study aimed to determine whether gender affects the myocardial metabolic response to lipid lowering in T2DM, and whether altering lipid [fatty acid (FA) or triglyceride] delivery to the heart would lower the elevated myocardial lipid metabolism associated with T2DM, and whether decreasing lipid delivery improves diastolic dysfunction in T2DM. The authors studied 78 T2DM patients (43 women) with positron emission tomography, echocardiography, and whole body tracer studies before and 3 months after randomization to metformin (MET), metformin + rosiglitazone (ROSI), or metformin + Lovaza (LOV). The results showed that in men, MET decreased FA clearance, which was linked to increased plasma FA levels, myocardial FA utilization and oxidation, and lower myocardial glucose utilization. In women, ROSI increased FA clearance, thereby decreasing plasma FA levels and myocardial FA utilization. Although LOV did not change triglyceride levels, it improved diastolic function, particularly in men. Group and gender also interacted in determining myocardial glucose uptake. Thus, in T2DM, different therapeutic regimens impact myocardial metabolism and diastolic function in a gender-specific manner. This suggests that gender should be taken into account when designing a patient’s diabetes treatment. Am J Physiol Heart Circ Physiol, December 2013. PMID: 24043256

smokers compared with 43% of control subjects (OR, 0.33). Ever daily smoking before PSC diagnosis was associated with older age at diagnosis (42 years vs 32 years). Ever daily smoking and being a coffee drinker at the age of 18 years were independently and negatively associated with PSC. Fewer female patients with PSC than control subjects reported ever use of hormonal contraception. Among female patients, there was a strong correlation between increasing number of children before the diagnosis of PSC and increasing age at diagnosis (r = 0.63). The authors conclude that coffee consumption and smoking might protect against development of PSC. In women, the disease might be influenced by hormonal factors. Clin Gastroenterol Hepatol, September 2013. PMID: 24076415

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research news

In this study, 31 patients were randomized to an early start group (ESG) or a delayed start group (DSG) exercise program. The ESG underwent a rigorous formal group exercise program for 1 h, three days/week, for 48 weeks. The DSG participated in this identical exercise program from weeks 24-48. Outcome measures included the

Unified Parkinson’s Disease Rating Scale (UPDRS), Walking Test (get-up-and-go), and the Beck Depression Inventory. The results did not show improvement in total UPDRS scores with early exercise. At week 48, the mean change from baseline total UPDRS score was 6.33 in the ESG versus 5.13 in the DSG (p = 0.58). However, patients randomized to the ESG scored significantly better on the Beck Depression Inventory, with a mean improvement of 1.07 points relative to those in the DSG (p = 0.04). The authors conclude that long-term, group exercise programs are feasible in the Parkinson’s disease population, with excellent adherence and minimal drop out. While the outcome measures used in the study did not provide strong evidence that exercise has a neuroprotective effect on motor function, earlier participation in a group exercise program had a significant effect on symptoms of depression. Parkinsonism Relat Disord, October 2013. PMID: 24209458

Baseline prostate inflammation associated with reduced risk of prostate cancer This study was performed to evaluate whether baseline acute and chronic prostate inflammation among men with an initial negative biopsy for prostate cancer (PCa) increased the risk of subsequent PCa detection in a clinical trial with systematic biopsies. A retrospective analysis was performed of 6238 men aged 50 years to 75 years with prostate-specific antigen levels between 2.5 ng/mL and 10 ng/mL and a prior negative biopsy in the REduction by DUtasteride of PCa Events study who completed a 2-year biopsy. PCa, acute prostateinflammation, and chronic prostate inflammation were assessed by central review. The results showed that acute and chronic inflammation and both were detected in 46 baseline biopsies (1%), 3931 baseline biopsies (63%), and 892 baseline biopsies (14%), respectively. At the 2-year biopsy, the prevalence of PCa was 14% (N = 900 patients). On univariable and multivariable analysis, both acute and chronic inflammation were found to be significantly associated with a lower PCarisk (acute univariable: odds ratio [OR], 0.65 [P < .001] and multivariable: OR, 0.75 [P = .012] and chronic univariable: OR, 0.61 [P < .001] and multivariable: OR, 0.65 [P < .001]). At the time of 4-year biopsy, only acute inflammation was found to be associated with a lower PCa risk. Cancer, December 2013. PMID: 24323568

Two low-dose levonorgestrel intrauterine contraceptive systems RCT This study evaluated the efficacy and safety of two low-dose levonorgestrel intrauterine contraceptive systems. Nulliparous and parous women aged 18-35 years with regular menstrual cycles (21-35 days) requesting contraception were randomized to 3 years of treatment with one of two levonorgestrel intrauterine contraceptive systems: 13.5 mg total content or 19.5 mg total content. The

primary outcome was the pregnancy rate, calculated as the Pearl Index. The results showed that overall, 1,432 and 1,452 women in the 13.5 mg intrauterine contraceptive system and 19.5 mg intrauterine contraceptive system groups, respectively, had a placement attempted. Over the 3-year study period, 0.33 pregnancies per 100 women-years (95% confidence interval [CI] 0.16-0.60) were observed with the 13.5 mg intrauterine contraceptive system compared with 0.31 per 100 women-years (95% CI 0.15-0.57) with the 19.5 mgintrauterine contraceptive system. At least partial expulsions occurred in 4.56% and 3.58% and discontinuation rates resulting from a reported adverse event occurred in 21.9% and 19.1%, respectively. Ten of the 20 pregnancies were ectopic. Serious adverse events included six cases of pelvic inflammatory disease and one partial uterine perforation. The authors conclude that both lower-dose levonorgestrel intrauterine contraceptive systems were effective. Obstet Gynecol, December 2013. PMID: 24240244

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Effects of a formal exercise program on Parkinson’s disease

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industry news Discovery of “teen gene” could hold promise for severe mental illnesses Douglas researchers identify first gene involved in adolescent brain development that may play a role in mental health vulnerability. It is known that during this teenaged phase of brain development, adolescents are particularly vulnerable to psychiatric disorders, including schizophrenia, depression and drug addiction. Researchers at the Douglas Institute Research Centre, affiliated with McGill University, have isolated a gene, DCC, which is responsible for dopamine connectivity in the medial prefrontal cortex during adolescence. Working with mice models, they have shown that dysfunction of this gene during adolescence has behavioral consequences which carry into adulthood. The breakthrough provides the first clues towards a fuller understanding of this important phase of brain development. Even subtle variations in DCC during adolescence produce significant alterations in prefrontal cortex function later on. To determine whether the findings of such basic research can translate to human subjects, researchers examined DCC expression in postmortem brains of people who had committed suicide. Remarkably, these brains showed higher levels of DCC expression - some 48 per cent higher when compared to control subjects.

CMA calls on federal government to create strategy against dementia dilemma Canada needs a national seniors care strategy to respond to issues such as the fast-growing dementia dilemma, according to the Canadian Medical Association (CMA). Dr. Chris Simpson, CMA President-elect, said Canada must move now to invest in a national seniors care strategy and join the 13 countries that already have dementia strategies in place. He added such a strategy is critical to helping our overtaxed health care system cope with about three quarters of a million Canadians already living with Alzheimer’s disease and other forms of dementia. Dementia currently costs the Canadian economy $33 billion a year in direct health-care costs or indirect costs of lost income of family members acting as caregivers. The Alzheimer’s Society of Canada predicts that by 2031, 1.4 million Canadians will have dementia, and by 2040 the annual cost to the economy will reach $293 billion. “We have the dubious distinction of being the only G8 country without a national dementia strategy. Meanwhile, our acute care hospitals are overflowing with patients awaiting long term care placement and our long-term care facilities are understaffed, under-spaced and underequipped to care for our most vulnerable seniors. This leaves patients and their families in limbo, struggling to fill these gaps in our system,” Dr. Simpson said.

Results of the Phase III START Trial in Non-Small Cell Lung Cancer Merck Serono, the biopharmaceutical division of Merck, announced that The Lancet Oncology has published results from the Phase III trial of its investigational MUC1 antigen specific cancer immunotherapy tecemotide (also known as L-BLP25) in patients with unresectable, locally advanced Stage III non-small cell lung cancer (NSCLC), known as the START trial. Data included in the publication, and first presented at the American Society of Clinical Oncology (ASCO) 2013, showed that the primary endpoint of overall survival (OS) was not met. Median OS was 25.6 months for patients in the tecemotide group compared with 22.3 months for those in the placebo group (adjusted HR: 0.88, 95% CI 0.75-1.03, p=0.123). The publication includes an exploratory analysis of a predefined subgroup of patients in the START trial who received tecemotide after concurrent chemoradiotherapy (CRT). Concurrent CRT is a combination of chemotherapy and radiotherapy given at the same time. Patients in this subgroup achieved a median OS of 30.8 months vs. 20.6 months in patients treated with placebo (n=806; HR: 0.78; 95% CI 0.64-0.95; p=0.016). In patients receiving sequential CRT followed by tecemotide or placebo a median OS of 19.4 months was observed for the tecemotide group compared with 24.6 months for the placebo group (n=433; HR 1.12; 95% CI 0.87-1.44; p=0.38). Tecemotide is an investigational MUC1 antigen-specific cancer immunotherapy designed to stimulate the body’s immune system to identify and target cancer cells expressing the cell-surface glycoprotein MUC1. MUC1 is expressed in many cancers, including NSCLC, and has multiple roles in tumor growth and survival.

IRCM researchers discover a protein’s critical role in the brain for anxiety disorders A team of Montréal researchers at the IRCM led by Dr. Nabil G. Seidah, in collaboration with Dr.William C. Wetsel’s team at Duke University in the United States, discovered that the protein PC7 plays a critical role in the brain by affecting certain types of cognitive performance such as anxiety, learning and emotional memory. Their results, recently published in the scientific journals Proceedings of the National Academy of Sciences (PNAS) and Nature, could have a significant impact on regulating behaviour related to anxiety disorders and trauma. The scientists found that PC7, the seventh member of the proprotein convertase family responsible for converting inactive proteins into their active states, plays a critical role in specific areas of the brain such as the hippocampus and amygdala, which are important for memory and emotional reactions and are involved in anxiety responses. The results of various behavioural tests in mice lacking PC7 revealed that while spatial memory remained intact, episodic and emotional memories were severely impaired. Episodic memory, the recollection of past events or experiences, can trigger a change in behaviour as a result of an event. “Collectively, these findings indicate that deletion of PC7 in mice could have substantial effects on certain types of cognitive performance,” concludes Dr. Seidah. “We believe that a drug targeting PC7 could increase levels of dopamine and BDNF in the brain, thereby normalizing behaviour. This discovery could be very significant for a number of conditions related to anxiety and trauma, such as bipolar disorder and posttraumatic stress disorder.”

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industry news New iPhone App Helps Patients Manage Medications and Improve Adherence STI, the leader in intelligent reimbursement solutions for the Canadian healthcare market, released the innoviCares app, designed to promote personal healthcare management and improve adherence to prescribed medications, available at the iTunes store for all registered innoviCares members. InnoviCares offers additional coverage for many original brand name medications and healthcare products and is provided to patients at no cost by STI, in partnership with participating pharmaceutical manufacturers. For many of the participating products, innoviCares provides members the choice to stay on original brand name medications. The newly released iPhone app gives members a digital version of their card and provides them with useful features, like easily actionable prescription refill alerts. These reminders are based on real intelligence driven from prescription possession data. In addition to the adherence alerts, other notable features include a pharmacy locator that maps the nearest preferred pharmacy who can serve the patient best, personalized benefits and savings, and an up-to-date list of what products are covered on the card. Patients simply bring their innoviCares card to their pharmacy when filling a prescription and the card works similar to their drug insurance card, providing coverage on participating products.

Making an Impact on the high-risk behaviour of teens For over 20 years, London Health Sciences Centre’s (LHSC) trauma program has been making an impact on the knowledge, attitudes and behaviours of teenagers to reduce drinking/drugging and driving through its Impact program. Impact aims to heighten teen awareness of the potential consequences of high-risk behaviour. Over the past year, LHSC’s injury prevention team conducted focus groups with over 200 grade 10 and 11 students at 10 London and surrounding area secondary schools. “We wanted a fresh understanding of all the issues affecting teenagers and driving in order to educate them about the consequences of high-risk behaviour in a way that is relevant and meaningful to them,” says Jane Harrington, injury prevention specialist, LHSC. The focus groups at secondary schools revealed that 55 percent of high school students surveyed drank alcohol in the past year, 22 per cent had used cannabis in the last year, 14 per cent had used opioid pain relievers in the last year and 8.7 per cent had smoked cigarettes. Acting upon student feedback, LHSC’s trauma program partnered with Josh Field Support Network, a non-profit, family based organization, with the mission of raising awareness of the dangers of distracted driving.

SIMPONI® I.V. (golimumab) becomes first fully human Anti-TNF infusion therapy

Janssen Inc. announced that Health Canada has approved SIMPONI® I.V. (golimumab) for infusion for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) in combination with methotrexate. SIMPONI® I.V. is the first and only fully human anti-tumour necrosis factor (TNF)-alpha infusible therapy approved in Canada to treat moderately to severely active RA. “The approval of golimumab for infusion offers patients living with moderately to severely active RA a new and effective treatment option with an infusion time of 30 minutes. In addition, it is dosed based on weight, which means it can offer patients a more tailored option,” said Dr. Edward Keystone, Mount Sinai Hospital. Approximately 300,000 Canadians are living with RA, a chronic, systemic inflammatory condition. RA is often characterized by symptoms of joint inflammation, stiffness and pain that, over time, spread to more joints. The approval of SIMPONI® I.V. is supported by findings from the Phase 3 Trial of Golimumab, an Anti-TNF-alpha Monoclonal Antibody, Administered Intravenously, in Subjects with Active Rheumatoid Arthritis Despite Methotrexate Therapy (GO-FURTHER).

Atrium Innovations Inc. acquired by Permira funds and a group of Québec investors Atrium Innovations Inc., a globally recognized leader in the development, manufacturing and commercialization of innovative, science-based natural health products, announced that it has entered into a definitive arrangement agreement with a company backed by the Permira funds whereby the Permira funds will acquire all the issued and outstanding common shares of Atrium, other than the shares to be rolled over by Fonds de solidarité FTQ and Caisse de dépôt et placement du Québec. Upon completion of the transaction, Atrium will be jointly owned by the Permira funds (75%), the Fonds (12.5%) and CDPQ (12.5%), before management equity programs. Atrium will maintain its head office in Québec, complete the expansion of the Québec manufacturing facility, and maintain current levels of employment, investment and R&D in Québec and Canada as well as ongoing community expenditures. The transaction represents a total enterprise value of approximately $1.1 billion, including the assumption of existing indebtedness, for 100% of Atrium. “The Permira funds understand and have a deep respect for Atrium’s Québec heritage which has been a key component of the Company’s historic success and will remain a highly important factor in the future”, said Pierre Laurin, Chairman of the Board of Atrium. “Our Board is pleased to recommend this transaction to our shareholders as it provides them with substantial and immediate cash value and is in the best interest of all stakeholders of the Company.” “Atrium has built over the years a great global platform and we intend to expand on that achievement”, said Pierre Fitzgibbon, President and CEO of Atrium. “Atrium intends to continue to pursue its growth strategy both organically and through acquisitions. The Permira funds’, the Fonds’ and CDPQ’s resources provide us the ability to accelerate our growth with the financial ability to expand globally. We look forward to working with our three partners and taking the Company to a new level to realize its full potential.”

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industry news Health Canada Privacy Blunder Undermines New Medical Cannabis Program The Canadian Association of Medical Cannabis Dispensaries (CAMCD) is outraged about Health Canada identifying 40,000 medical cannabis patients and producers by sending them correspondence with “Marihuana Medical Access Program” in the return address, contrary to their standard procedure. “This privacy breach violates patient rights and undermines Health Canada’s attempts at reforming their medical cannabis program,” said Adam Greenblatt, CAMCD president. “If Health Canada is trying to instill confidence in a mail-order distribution system for medical cannabis, they are not off to a good start.” The correspondence in question contained informational materials about the reasons behind Health Canada’s regulatory reform, which ironically includes an increased risk of home invasion for patients who grow their own medical cannabis. “Patients are already very concerned that their personal medical information will be turned over to police and realtors when Health Canada revokes their permits next year,” continued Greenblatt. “These patients are accustomed to producing their own supply or accessing a storefront medical cannabis dispensary, yet both options are prohibited under Health Canada’s new regime.” The Deputy Minister of Health issued a bewildered apology, but CAMCD is unimpressed. CAMCD was established to promote a regulated, community-based approach to medical cannabis access, and to support dispensaries in providing the highest quality patient care.

Health Canada Approves Treatment for Relapsing Remitting Multiple Sclerosis Genzyme, a Sanofi company, announced today that Health Canada has approved AUBAGIO® (teriflunomide) 14 mg as monotherapy for the treatment of patients with relapsing remitting multiple sclerosis (RRMS) to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability. “There are many patients who simply cannot tolerate injections and have had no simple, effective, once daily oral medication until now,” said Dr. Mark Freedman, Director, Multiple Sclerosis Research Unit and Professor of Neurology and Senior Scientist at the University of Ottawa and Ottawa Hospital Research Institute. “As a new oral treatment option, AUBAGIO is an important advancement for the MS community and may help improve quality of life for people living with this debilitating disease.” The Health Canada approval was based on efficacy data from two Phase III clinical trials - TEMSO (TEriflunomide Multiple Sclerosis Oral) and TOWER (Teriflunomide Oral in people With relapsing remitting multiplE scleRosis). In the TEMSO trial, AUBAGIO 14 mg significantly reduced the annualized relapse rate (p=0.0005) and the time to disability progression (p=0.0279) at two years versus placebo in patients with RRMS. In the TOWER trial, AUBAGIO 14 mg significantly reduced the annualized relapse rate (p=0.0001) and the time to disability progression sustained for 12 weeks (p = 0.0442) was statistically significantly reduced versus placebo in patients with RRMS.

New ADHD treatment now available in Canada Canadian families now have a new option to help manage their child’s Attention Deficit Hyperactivity Disorder (ADHD); INTUNIV XR (guanfacine hydrochloride extended release tablets), a new and different class of ADHD medication, is now available in Canada for the treatment of ADHD in children ages 6 to 12. The new once-daily treatment is approved for use either as a stand-alone treatment for ADHD or in addition to stimulants for children not responding optimally to stimulants. Between 500,000 to 1.2 million Canadian children have ADHD. In a recent survey of 311 parents of children with ADHD, more than half stated that their child is not well controlled on current medication. Almost one in ten (8 per cent) reported their child is not controlled, and a further 44 per cent stated their child is only partially controlled, suggesting many children may not be receiving the best possible care to manage their ADHD symptoms. “Stimulants are the go-to treatment option for ADHD as they successfully manage the symptoms of most children, but not all respond as well as hoped.” says Dr. Kenny Handelman, psychiatrist at the Oakville Trafalgar Memorial Hospital and expert in ADHD. “INTUNIV XR works differently than all other approved ADHD treatments. What’s more, it can be used as a stand-alone treatment, or in combination with stimulant medication - opening the door to new choices for children still struggling with their ADHD.” INTUNIV XR is a selective alpha2A-adrenergic receptor agonist, providing an alternative treatment for children (6 to 12 years old) in whom response to stimulant therapy has been suboptimal.

CAMH and Assurex Health launch joint venture to advance personalized medicine The Centre for Addiction and Mental Health (CAMH), Canada’s leading hospital for mental health, and Assurex Health, a global leader in personalized medicine, have signed an agreement for a joint venture to bring the benefits of this treatment approach to more Canadians. The personalized approach helps to match the right medication at the right dose for each patient, based on their genetic makeup. Using Assurex Health’s GeneSight panel, physicians can easily see which psychiatric medications are likely to be effective for each patient and which ones are not, often avoiding treatment failure and side effects. “This partnership between CAMH and Assurex Health is essential to advance the widespread use of personalized medicine in psychiatry, and improve health care for Canadians who need medications for mental health problems,” said Dr. James Kennedy, head of the Tanenbaum Centre for Pharmacogenetics at CAMH. This approach is a game-changer from the current trial-and-error approach to prescribing, which results in many patients having to try different psychiatric medications, each with potential side-effects, before the best medication for them can be determined. In the U.S., Assurex Health data shows a 70 per cent improvement in depressive symptoms when GeneSight testing is used to predict patient response to antidepressants versus treatment as usual, and a 28 per cent reduction in health care costs.

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Curcumin Active with Longvida® Curcumin: Exclusively available in Canada from AOR

Curcumin Active 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 Curcumin Active delivers a therapeutically effective dose of curcumin, the equivalent of over 13g of a regular 95% curcumin extract. This would require taking 30 capsules of regular 95% curcumin extract, or more than 100 capsules of 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 at a low dose of 80mg of Longvida® curcumin. Imagine the potential results of longer-term supplementation! Curcumin Active 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). Curcumin Active 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: 80034700 Serving Size: Longvida® Optimized Curcumin* (from Curcuma longa root 25-30:1)

1 Capsule 133.3 mg

Non-medicinal ingredients: ascorbyl palmitate, microcrystalline cellulose, soy lecithin, stearic acid, maltodextrin, silicon dioxide. Capsule: hypromellose. * LONGVIDA® is a registered trademark of Verdure Sciences Inc. International patent pending.

Adult Dosage: Take 1 to 2 capsules daily, 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.

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References: Begum AN et al. J Pharmacol Exp Ther. 2008 Jul;326(1):196-208. Belkacemi A et al. Expet Rev Mol Med. 2011 Nov; 13(e34):1-15. Bisht S et al. Lab Invest. 2011 Sep;91(9):1383-95. Buhrmann C et al. J Biol Chem. 2011 Aug 12;286(32):28556-66. Cheng AL et al. Anticancer Res. 2001 Jul-Aug;21(4B):2895-900. Dadhaniya P et al. Food Chem Toxicol. 2011 Aug;49(8):1834-42. DiSilvestro RA et al. Nutr J. 2012 Sep 26;11:79. Frautschy, SA. 38th Annual Meeting of the Society of Neuroscience, Washington DC, November 15, 2008. Frautschy, SA et al. 39th Annual Meeting of the Society of Neuroscience , Chicago, IL October 2009. Frautschy, SA et al. 39th Annual Meeting of the Society of Neuroscience , Chicago, IL October 2009. Gandapu U et al. PLoS One. 2011 6(8):e23388. Gota VS et al. J Agric Food Chem. 2010 Feb 24;58(4):2095-9. Lao CD et al. BMC Complement Altern Med. 2006 Mar 17;6:10. Mito S et al. Biol Pharm Bull. 2011 34(7):974-9. Xie L et al. Int Immunopharmacol. 2011 Mar;11(3):323-30. Yekollu SK et al. Diabetes. 2011 Nov;60(11):2928-38.

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calendar FEBRUARY

MARCH

February 20-22 2014 Scientific Meeting of the Canadian Pediatric Endocrine Group Organized by: UBC Montreal, QC For more information, visit interprofessional.ubc.ca/CPEG2014

March 1-2 Individualized Nutrition: Addressing Advances in Metabolic Individuality Organized by: Seroyal Vancouver, BC For more information, visit www. seroyalseminars.com

February 22 Personalizing Nutritional Protocols Organized by: Metagenics Rogers, AR For more information, visit www. metagenics.com

March 6 Human Microbiome Organized by: Seroyal Online Webinar For more information, visit www. seroyalseminars.com

February 22 Complex Homeopathy and Constitutional Diagnosis made easy Organized by: Pascoe Toronto, ON For more information, visit http://www. pascoecanada.com/en/events/8/

March 7 Assessment & Management of the Patient with Complex Chronic Pain 2014 Organized by: CFPC Vancouver, BC For more information, visit http://www. cfpc.ca/UpcomingEvents/

February 22-24 MTC 2 â&#x20AC;&#x201C; Advanced Clinical Patient Evaluation and Treatment Organized by: Seroyal Toronto, ON For more information, visit www. seroyalseminars.com

March 8 Complex Homeopathy and Constitutional Diagnosis made easy Organized by: Pascoe Vancouver, BC For more information, visit http://www. pascoecanada.com/en/events/8/

February 25-March 1 2014 Scientific Conference of the Canadian Spine Society Organized by: Spine Canada Lake Louise, AB For more information, visit spinecanada.ca

March 27 LEAP (Learning Essential Approaches to Palliative and End-of-Life Care) Organized by: CFPC Bathurst, NB For more information, visit http://www. cfpc.ca/UpcomingEvents/

February 26 2014 Brain FHT Organized by: CFPC Peterborough, ON For more information, visit http://www. cfpc.ca/UpcomingEvents/ February 26-March 1 2014 Annual Scientific Meeting of the Canadian Rheumatology Association Organized by: Rheumatology Association Whistler, BC For more information, visit rheum.ca/en/ events

March 28 Diabetic Food Canada Organized by: CFPC Sudbury, ON For more information, visit http://www. cfpc.ca/UpcomingEvents/

APRIL

April 3 Autism and ADHD: Holistic Approach Organized by: Seroyal Online Teleconference For more information, visit www. seroyalseminars.com

April 5 Complex Homeopathy and Constitutional Diagnosis made easy Organized by: Pascoe Ottawa, ON For more information, visit http://www. pascoecanada.com/en/events/8/ April 10-14 CHFA West Conference Organized by: CHFA Vancouver, BC For more information, please visit: https:// www.chfa.ca/tradeshows/ 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 25-29 Canadian Conference on Medical Education Organized by: CCME Ottawa, ON For more information, visit mededconference.ca/ccme2014/ February 26-March 1 2014 Annual Scientific Meeting of the Canadian Rheumatology Association Organized by: Rheumatology Association Whistler, BC For more information, visit rheum.ca/en/ events

MAY

May 23-25 First Line Therapy Certification Organized by: Metagenics Toronto, ON For more information, visit www. metagenics.com

JULY

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

24 www.ihpmagazine.com l February / March 2014

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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 l r Pe G ts N une en’s m P d u n al Ho Co 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

Curcumin Active from AOR Curcumin Active contains Longvida® curcumin, the most bioavailable curcumin on the market with bioavailability increases of over 100-fold. Curcumin Active provides curcumin’s plethora of benefits including relieving inflammation and joint pain in a low dose of 1 to 2 capsules a day. Longvida® curcumin is exclusively available in Canada from AOR.

Carlson MedOmega Fish Oil Carlson MedOmega lemon-lime liquid provides the important omega-3s EPA & DHA which current research suggests support cardiovascular health and brain function. Freshness, potency & purity of Carlson fish oils are guaranteed! www.carlsonlabs.com

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.

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.

Fast Recovery 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!

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product profiles

Legend

The Clear Change™ Metabolic Detoxification Program: New Peach Flavor The Clear Change Program is a scientifically designed, 10-day metabolic detoxification program that supports the body’s natural cleansing processes to promote overall health and well-being. It combines a simple eating plan with over 20 years of successful clinical use with effective, targeted nutritional support—including AdvaClear® and UltraClear Renew™. It’s simple for you to dispense and includes easy-to-follow patient guidelines and online resources (webinar, recipes, FAQs, and email support). Promotional materials are also available. Help your patients feel better and thrive! UltraClear Renew is now available in refreshing peach flavor. • 800.692.9400 US • 800.268.6200 Canada • Metagenics.com or clearchangeprogram.com.

Metagenics Launches SeroSynTM to Nutritionally Support a Positive Mood* SeroSyn is an advanced formula featuring clinically effective levels of L-5-HTP and L-theanine to support healthy levels of specific neurotransmitters. This formula is enhanced with standardized extracts of Asian ginseng and Chinese skullcap to target the stress response, cognition, and mood, which are closely intertwined. Specific B vitamins are added to support methylation, homocysteine metabolism, and healthy neurological function.* SeroSyn is available in 30 and 90 capsule bottles. Metagenics.com • 800.692.9400 US • 800.268.6200 Canada

NEURAPAS® balance – Vitality and Motivation NEURAPAS® balance is a well-tolerated herbal remedy that produces favorable results in the treatment of mental illnesses, particularly those with imbalanced mood, because of its well-balanced composition and various pharmacological effects. In addition, because of the unique synergy – meaning smaller amounts of St. John’s wort achieve the same therapeutic effect NEURAPAS® balance has been shown to have no side effect on liver enzymes at therapeutic doses. Therefore the concern for side effects traditionally observed with St. John’s wort is not a problem with NEURAPAS® balance.

BASENTABS pH-balance PASCOE® 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 26 www.ihpmagazine.com l February / March 2014

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product profiles

Legend

Echinasyr Echinasyr is a liquid-based formula that comes in a convenient 125 ml bottle. A unique and patented immunostimulant, the formulation is derived from pure Echinacea purpurea extract, and is a trusted product in the UNDA homeopathic line.

Biotherapeutic Drainage™ Immune Support Biotherapeutic Drainage™ Immune Support kit contains UNDAs 3, 20 and 50 to support the intestinal barrier. This 3-week support kit is convenient and easy-to-use and also contains Imu-gen for phytonutrient support.

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

Mag-Matrix Liquid™ Mag-Matrix Liquid™ is a unique blend of highly absorbable magnesium sources- magnesium glycinate, malate and citrate. Sweetened with xylitol and a subtle but pleasing natural lemon flavour.

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.

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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

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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”

30% Omega-3

DHA

775 mg

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

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cover story

FertilityCare Toronto by Philip Rouchotas, Msc, ND photographs by Bruce Redstone

FertilityCare Toronto A Restorative Approach To Women’s Health

FertilityCare Toronto is a holistic- minded women’s health center with the goal of restoring couples’ fertility, as naturally as possible and in harmony with the natural cycles of a woman’s body. Located at Coxwell and Danforth in downtown Toronto, the center’s services are delivered by a diverse, interdisciplinary team of health practitioners specially trained in the medical applications of the FertilityCare System, a standardized method of fertility awareness-based natural family planning, and NaPro Technology (natural procreative technology). Practitioners affiliated with the center include medical doctors, naturopathic doctors, a registered nurse, and lay practitioners with advanced training in guiding women in the FertilityCare System and NaPro Technology. NaProTechnology is a scientifically-based and well-researched reproductive health care service that cooperates with and restores reproductive function. The FertilityCare System of charting biomarkers provides the basis for the evaluation and treatment of women’s reproductive health by the NaProTechnology approach. FertilityCare Toronto provides services to women seeking alternatives for the treatment of concerns ranging from PMS, dysmenorrhea, irregular menstrual cycles, pregnancy care and post-partum issues including post-partum depression, as well as infertility; however approximately 50% of patients visit the center with fertility-related concerns. For readers who may not be familiar with the system, the FertilityCare System consists of tracking and classifying specific biomarkers of fertility, namely the presence and qualities of cervical mucus, in a precise, systematic manner. These biomarkers are used to give an indication of changing estrogen and progesterone levels, as well as the timing and quality of ovulation. For example, the presence of spotting or brown bleeding can indicate a progesterone deficiency. Characteristics of cervical mucus that are collected include the sensation of mucus, colour, consistency, and length of stretch. An absence or low February / March 2014 l www.ihpmagazine.com 31

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cover story production of cervical mucus may indicate low estrogen levels and/ or problems with ovulation. The last day that cervical mucus is present during the cycle is termed “peak day,” and is used to estimate the time of ovulation. Ovulation has been shown to occur within 36 hours of “peak” in 95% of women. In addition to systematic data collection, the FertilityCare System uses a standardized method for the classification and interpretation of this data, with a view to medical applications. The FertilityCare System was developed over the last thirty years by Dr Thomas Hilgers MD, an obstetrician based out of Creighton University in Nebraska. Dr Hilgers studied the correlation of biomarkers with objective hormone changes in a woman’s body, identifying specific disturbances and/ or deficiencies present in particular pathologies such as endometriosis and polycystic ovarian syndrome (POCS). The FertilityCare system of charting biomarkers provides the foundation for the application of NaPro Technology, an advanced medical system of fertility care that restores reproductive function. For instance, Dr Hilgers identified at least four different patterns or types of luteal phase deficiency, and established his own reference ranges for optimal estradiol and progesterone levels, which are now used by NaProtrained physicians worldwide. Dr Hilgers established the concept of an integrated hormone profile to assess estrogen and progesterone levels over the course of the cycle, with measurement periodically or every second day of the follicular and luteal phases to assess serum estradiol and progesterone, rather than relying on a single day 22 progesterone measurement. Such a strategy allows for a more accurate assessment of hormone areas under the curve (AUC) during the entire luteal (or follicular) phase. Dr Hilgers advocated the correction of hormone disturbances relying as much as possible on bioidentical hormones such as progesterone, hCG, and estradiol. Recently, IHP had the privilege of speaking with several members of the Toronto-based team. Dr Julia Cataudella MD, CCFP, FCP, FCMC is a medical doctor based out

of the center. As a graduate of Queen’s University School of Medicine, and the University of Toronto with a specialty in Family Medicine, Dr Cataudella sees the the FertilityCare System and NaPro Technology as a tool to truly understand and solve women’s health concerns without suppressing the body’s normal function and hormone physiology. Dr Cataudella is also a member of the International Institute of Restorative Reproductive Medicine (iirrm.org), a network of health care professionals and researchers who are committed to this restorative approach. Dr Cataudella emphasizes the restorative nature of the FertilityCare System as a method of “cooperatively restoring a woman’s fertility and/ or menstrual cycle.” Application of the FertilityCare System) can restore feedback in hormone systems, thereby correcting the underlying problems affecting women’s health, without resorting to suppressive treatments such as the oral contraceptive pill (OCP). Targeted use of bioidentical hormones in sync with a woman’s cycle corrects disturbances in a way that respects the body and safeguards fertility. Dr. Cataudella emphasizes that timing of hormone administration is key in achieving outcomes, and analysis of the woman’s chart is used the help determine this. The FertilityCare System system is a proactive approach, and while it requires women to invest some time in learning the charting method, the end result is women feeling empowered, dignified, and in control of their fertility. This system can also be applied to a range of other women’s health issues as well, ranging from PMS, to irregular cycles, to endometriosis and PCOS. In her system of practice, Dr Cataudella embodies a holistic philosophy, cognizant of treating the whole person and addressing the underlying cause of disease. She eloquently describes some of the common strategies used in the conventional approach to women’s health as suppressive and near-sighted. A common example includes prescription of the OCP as a panacea for concerns ranging from teen-PMS and acne to irregular cycles and dysmenorrhea. Such a strategy shuts down the hypothalamuspituitary-ovary (HPO) axis, suppresses ovulation, and inhibits normal production

Photos: The hardworking women of the FertilityCare Toronto centre.

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cover story of estrogen and progesterone, while failing to address the true cause of illness. Dr Cataudella is also critical of the long-term effects of such a strategy with respect to metabolic disturbances, cardiovascular risk including blood clots, and risk of carcinogenesis. Similarly, the conventional approach to the treatment of infertility tends to rely heavily on drugs and invasive techniques that override the woman’s own body and reproductive system, while ignoring potential long-term effects on disease risk. In keeping with her holistic approach, Dr Cataudella complements her practice of NaPro Technology with a developed interest in natural agents. She incorporates a variety of natural strategies in her recommendations to patients, including specific dietary advice and prescription of select natural health products. She recommends a low glycemic diet higher in protein for patients with PCOS, as well as a hypoallergenic diet (gluten and/ or dairy free) as well as the GAPS diet (Gut and Psychology Syndrome diet) to address the autoimmune components of endometriosis and/ or PCOS. Supplements that may be recommended to patients include inositol, chromium, chaste tree berry, biotin, and vitamin D. For men, Dr Cataudella may recommend coenzyme Q10, alpha lipoic acid, L-carnitine, and N-acetylcysteine to enhance sperm parameters. Another more novel, innovative therapy that is being increasingly utilized by NaPro- trained physicians in the treatment of conditions such as PCOS and endometriosis is Low Dose Naltrexone (LDN), a therapy that is also commonly used by naturopathic doctors in the treatment of cancer. Administration of a low, short-acting bedtime dose of naltrexone boosts early morning (rebound) endorphin production and/ or receptivity. This increase in baseline endorphin activity has been shown to support normal immune and endocrine function in conditions such as endometriosis. High dose, daytime naltrexone (50mg) may also be used to treat conditions associated with excess opioid tone, which may inhibit ovulation. In addition, Dr Cataudella cross-refers many patients with a naturopathic doctor affiliated with the center, Dr Nora Pope, ND. Dr Pope has been involved with the center for over twenty years, first as a volunteer and organizational leader, and later as a charting instructor, practitioner, and naturopathic doctor. Dr Pope referred her first patient to Dr Cataudella as a result of epilepsy that followed a cyclical pattern, indicating hormonal involvement and a possible role for progesterone therapy. Since then, they have shared many patients. Dr Pope has also completed advanced training in NaPro Technology, travelling to the United States to complete her training as a Medical Consultant Auditor at Dr. Hilgers’ center. Dr Pope uses her naturopathic tools, including botanicals, nutrients,

classical homeopathy, and acupuncture, to enhance the specific effects of NaPro Technology with respect to hormones and the reproductive system, as well as to enhance patients’ overall health status that may be interfering with their reproductive function. In addition, other members of the team include Karen Hemingway CFCS, Executive Director; Margaret Smith, RN, CFCE, Education Program Director; Sylvia Heald, BEd, CFCP; Vania Branker MSc, FCP; Denise Chun, BEd, CFCP; Laura Ostoya FCP; and Natalie Mahon, BEd, FCPI. Affiliated with the center but practicing independently are two other medical doctors trained in NaPro Technology: Dr Elizabeth Tham MD, CCFP, FCFP, CFCMC and Dr Maria Wolfs MD, FRCPC, NFPMC. Dr Tham has a family practice with a focus on NaPro Technology located in Etobicoke, while Dr Wolfs is an endocrinologist at St. Michael’s Hospital in Toronto. Dr Tham has an active research interest, and has published work on the effectiveness of NaPro Technology in the Canadian Family Physician (Tham 2012). In brief, Tham et al analyzed data from a cohort of 108 couples receiving care using NaPro Technology. Baseline characteristics of the cohort were that 18% had reported having two or more previously unexplained miscarriages. The average female age was 35.4 years, and couples had been attempting to conceive for a mean of 3.2 years. Results showed that the cumulative adjusted proportion of first live births for those completing up to 24 months of NaPro treatment was 66 per 100 couples. The cumulative adjusted proportion of first conceptions was 73 per 100 couples. Of the 51 couples who conceived, 12 couples (24%) conceived with Creighton model charting instruction alone, 35 (69%) conceived with charting plus NaPro medical treatment, and 4 (8%) conceived after additional surgical treatment. There are also NaPro researchers based out of the United States, Ireland, Africa, and Australia. NaPro researchers are connected through membership in the International Institute of Restorative Reproductive Medicine (IIRRM). For more information, please visit iirrm.org. We congratulate FertilityCare Toronto on their work and dedication to making NaPro services available to women here in Canada. References FertilityCare.net. New Treatment Strategies. Low Dose Naltrexone. Patient Information. URL: http://www.fertilitycare.net/documents/ LDNInfoAug13aa.pdf Accessed 29 January 2014. Tham E, Schliep K, Stanford J. Natural procreative technology for infertility and recurrent miscarriage: outcomes in a Canadian family practice. Can Fam Physician. 2012 May;58(5):e267-74. February / March 2014 l www.ihpmagazine.com 35

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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.

clinic profile

Tapout Training Center Peak Performance Care For Elite Athletes By Christopher Habib, NDâ&#x20AC;&#x201A; Photographs by Bruce Redstone

HP Magazine usually features a team of health practitioners. This clinic profile is different in that we are featuring a single practitioner that is performing such a unique and impressive style of medicine that we simply couldnâ&#x20AC;&#x2122;t pass up the opportunity to highlight his work. Dr. Callum Cowan, ND, has been practicing out of the Tapout Training Centre in Burlington for the last couple of years. The Tapout Training Centre is part of a network of facilities with additional locations in Las Vegas and Los Angeles, where elite Mixed Martial Artists (MMA) and other high-level athletes train.

Dr. Cowan began working with professional athletes soon after obtaining his license. His focus has been on Mixed Martial Artists, Boxers, and Hockey players. The stakes are high for most of the athletes he works with. For the fighters, every fight is a huge deal for their career. In the fight business, you are only as good as your last fight because that is the fight that people tend to remember, and competition is fierce. Fighters need to be winning, and winning impressively to climb the ranks. Dr. Cowan began by working closely with two highly ranked professional fighters who had difficult fights coming up. He identified gaps in their health as well as opportunities for enhanced

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clinic profile

performance. He dealt with numerous aspects of their care and utilized various components of naturopathic practice to help prepare them for their fights. The goal was always to maximize health and performance. Both fighters came out with decisive and dominant victories over their opponents, which elevated them in the rankings. The fighters were extremely pleased with the improvements in their performance and Tapout was impressed with what Dr. Cowan had to offer. From there he was able to actually setup his clinic in the upper level within their 16,000 square feet world-class training facility. Since then, Dr. Cowan has played a key role in the success of a number of athletes. Most recently, one of Dr. Cowanâ&#x20AC;&#x2122;s fighters set a UFC record in his impressive win by landing the most number of significant strikes in a bout in UFC history.

One of the most unique and interesting parts of Dr. Cowanâ&#x20AC;&#x2122;s work is his involvement in the weight-cutting and refueling process. When it comes to Mixed Martial Arts and Boxing, athletes compete within a narrow weight class. Typically, the fighters are weighed in on a Friday afternoon and will have their fight scheduled on a Saturday night. The standard process is that they will lose large amounts of weight before their weigh-in and then try to regain as much as possible to be able to perform at their best by the time of the fight. A typical weight cut can be anywhere from 10 to 30 lbs. It can be extremely unhealthy and dangerous, as it could involve some extreme methods like sitting in a sauna for long periods of time. If done properly, weight-cutting can provide a big advantage, but if not, it can put fighters at a disadvantage and can cause huge declines in their performance. If a fighter misses their target weight, it is damaging to their reputation and their career as it is seen as being very unprofessional. They may also have to give up some of their purse money to their opponent or have the bout cancelled; it is up to the opponent

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clinic profile

to decide. Dr. Cowan works very closely with each fighter and prepares a complete and detailed plan for the entire fight camp, weight-cut and refueling process. Dr. Cowan explains that: “The key is planning things out properly, keeping it simple, and tailoring the methods to each individual.”

When asked whether he gets nervous before his fighters compete, Dr. Cowan says that he forms such a close relationship with his athletes that he often feels like he is in the fight alongside them. Currently, Dr. Cowan works with a number of elite fighters that compete in the UFC (the premier organization) and with other professional organizations. He also works with many developing and professional Boxers and Hockey players. He obtains his referrals through wordof-mouth and has an extremely committed patient base, in that every athlete he’s worked with is still seeing him. In the future, he hopes to continue growing his roster of elite level professional Mixed Martial Artists, Boxers, and Hockey players and to continue playing a key role in their success. Dr. Cowan is grateful for his opportunity at the Tapout Training Centre and for being able to work closely with athletes that compete in the sports that he is so passionate about. Despite getting offers from other professionals to partner up in practice, Dr. Cowan has not yet found the right fit. We at IHP wish him continued success in his unique approach.

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clinic profile

Tapout Training Centre Callum Cowan, ND 5041 Fairview Street Burlington, ON L7L 4W8 289-828-1979 drcallumcowan@gmail.com www.drcallumcowan.com

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The Journal Of

Integrated Healthcare

Practitioners 1

p49

Neurodegeneration A complication of longstanding multiple sclerosis (MS) By Eric Muradov, ND

p57

Hypertension

Management Considerations By Elaine Lewis, ND

3 CE

p65

Demystifying Bioidentical Hormones

A Review Of BHRT Use In Clinical Practice With Respect To Menopausal Concerns By Tannaz Mokhtari, BSc, ND and Ishita Patel, HBSc, Pharm D, RPH

p73

Mistletoe Therapy

Improving Outcomes In Complementary Cancer Care By Sarah Vanderheyden, RPN and Heidi Fritz, MA, ND

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editorâ&#x20AC;&#x2122;s letter

Deep Freeze

outhern Ontario has experienced one of the worst winters in living memory! We typically see -20C a handful of times per year, yet this winter such temperatures have been the norm. We hope wherever home may be for you that you have found a way to keep warm this winter!

FertilityCare Toronto empowers women to educate themselves as to their menstrual cycle, delivering a natural and highly effective solution for improving pregnancy outcomes. In conjunction with select use of natural health products, as well as prescription of bioidentical hormones as required, the FertilityCare team is helping to overcome an emerging epidemic of the 21st century; infertility. Dr Julia Cataudella, MD, is one of several physicians across the country serving as the medical supervisor for a system that includes a comprehensive team of trained support staff working in unison to deliver the impressive outcomes of the system of care. We are excited to present her team and centre to you. Dr Callum Cowan, ND, and the Tapout training centre have been featured as this issues clinic profile. A unique selection for IHP as a clinic to profile, Dr Cowan focused his attention from an early stage of his career on working with elite athletes. With a principle focus on mixed martial artists and hockey players, Dr Cowan applies principles of naturopathic medicine to help these athletes maximize performance. We are excited to present an important lineup of feature articles. Eric Muradov, ND, follows- up on a 2010 submission covering multiple sclerosis with a submission focused on the neurodegeneration that develops in conjunction with demyelination that characterizes the disorder. Tannaz Mokhtari, ND, and Ishita Patel, Pharm D provide an excellent comparative review of synthetic versus bioidentical hormone therapy. Elaine Lewis, ND, eloquently summarizes new guidelines governing hypertension management. Sarah Vanderheyden, RPN, and Heidi Fritz, MA, ND, provide the issues continuing education lesson, reviewing existing evidence of mistletoe therapy as an adjunctive treatment in cancer management. Best Regards, Philip Rouchotas, MSc, ND Editor-in-Chief We invite questions or comments. philip@ihpmagazine.com

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Integrated Healthcare

Contributors Christopher Habib, ND, Philip Rouchotas, MSc, ND Eric Muradov, ND, Sarah Vanderheyden, RPN, Heidi Fritz, MA, ND, Tannaz Mokhtari, ND, Ishita Patel, Pharm D, Elaine Lewis, 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

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

Published by IHP Magazine

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

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

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

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

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

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

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

Berchman Wong, ND 718 - 33 Canniff St Toronto, Ontario M6K 3M5 berchman.nd@gmail.com Betty Rozendaal, BES, MA, ND Thornhill Naturopathic Health Clinic 12A Centre Street Thornhill, Ontario L4J 1E9 drbetty@thornhillnaturopathic.ca Brock McGregor, ND McGregor Naturopathic 220 St Clair Street Chatham, Ontario N7L 3J7 drbrock@mcgregornd.com Carol Morley, ND Zawada Health 201 City Centre Drive, Suite 404 Mississauga, Ontario L5B 2G6 info@zawadahealth.com Christopher Knee, ND, MSc The Dempster Clinic â&#x20AC;&#x201C; Center for Integrated Medicine 97 Scollard Street Toronto, Ontario knee.christopher@gmail.com Claire Girgis, ND Zawada Health 201 City Centre Drive, Suite 404 Mississauga, Ontario L5B 2G6 claire@zawadahealth.com

David Miller, BSc, ND 662 Gustavus Street Port Elgin, Ontario N0H2C0 drdavend@yahoo.ca

Faryal Luhar, ND Healthwise Wellness 4250 Weston Rd Toronto, Ontario M9L 1W9 ndluhar@hotmail.com Heidi Fritz, MA, ND Canadian College of Naturopathic Medicine 1255 Sheppard Ave East Toronto, Ontario M2K 1E2 hfritz@ccnm.edu Isaac Eliaz, MD, MS, LAc Amitabha Medical Clinic & Healing Center 7064 Corline Ct #A Sebastopol, California 95472-4528 ieliaz@sonic.net Jacob Scheer, DC, ND, MHSc 2100 Finch Ave. W. #206 North York, Ontario M3N 2Z9 Jacob.Scheer@utoronto.ca

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

Jiselle Griffith, BSc, ND The Health Hub Integrated Clinic 12 Irwin Ave, Suite 200 Toronto, Ontario jiselle@healthhubclinic.com

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

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

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

Judah Bunin, BSc, MSc, ND, DrAc Fredericton Naturopathic Clinic 10-150 Cliffe St Fredericton, New Brunswick E3A0A1 frednatclin@yahoo.ca

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

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

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

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

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peer review

Kelly Brown, BSc, ND Clinic One 286 McDermont Avenue Winnipeg, Manitoba R3B 1H6 drkbrownnd@gmail.com

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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editorial board

IHP Editorial Board Members The purpose of our Editorial Board is to help

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

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

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

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

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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 evidenceguided treatment. Dr. Parmar is also active in writing and lecturing in the fields of clinical hyperthermia, the tumour microenvironment, and integrative oncology. He continues to serve as a board member for the Oncology Association of Naturopathic Physicians, a position he has held since 2008. He is licensed by the College of Naturopathic Physicians of B.C.

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

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

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The Journal of IHP

Neurodegeneration

A complication of longstanding multiple sclerosis (MS) By Eric Muradov, ND Eric Muradov, ND 8712 149 st, Edmonton, Alberta T5R 1B6 info@drericmuradov. com

Abstract Approximately 85% of patients with multiple sclerosis are first affected by relapsing and remitting disease, with periods of acute exacerbation. The majority of these patients also develop a secondary course of disease, characterized by progressive, gradual loss of function. These two types of disease processes appear to be driven by independent mechanisms, and clinicians should address not only the underlying inflammatory stimuli to reduce periods of exacerbation, but also address targets of chronic neurodegeneration. This article focuses on four key areas with regards to neurodegeneration: mitochondrial dysfunction, cerebrovascular function, iron deposition, and excitotoxicity, in order to prevent the onset of or decrease the severity of progressive MS.

Introduction It is well accepted that multiple sclerosis (MS) is Th1/Th17 mediated autoimmune disease (Korn 2008). In MS about 85% of patients initially experience a relapsing-remitting course of disease (relapsing-remitting multiple sclerosis, RRMS), which is characterized by acute episodes of neurological deficit called â&#x20AC;&#x153;relapses.â&#x20AC;? These episodes commonly include limb weakness, vision changes, ataxia and sensory disturbances. Relapses are followed by periods of remission, which usually have partial or near complete restoration of function. After a variable number of years, the majority of these patients develop a secondary progressive disease course where disability slowly accrues despite often having fewer attacks, suggesting that other mechanisms are involved in progression. Furthermore, commonly used anti-inflammatory medications such as interferon beta have minimal effect on inhibiting the neurological decline, implying that this process is more complex than inflammation alone (Su 2009). Latency to commencement of progressive MS varies greatly. One study demonstrated a broad range from one to 36 years with a mean of five years in the quickest 25% to greater than 15 years in the slowest 25% (Scalfari 2013). Male sex, older age of onset (>30), and high early yearly relapse frequency (>3) were predictors for more rapid entry into progressive MS (Scalfari 2013). Therefore, because some patients may convert quickly into progressive MS, preventing progressive MS should be a primary goal when treating all MS patients, and especially if they are at higher risk. Relapses are considered to be the clinical manifestation of acute inflammatory demyelination in the CNS, and progression

of disability is thought to reflect chronic demyelination, axonal loss and neuronal death (Luessi 2012). MS should be viewed as both an inflammatory and a neurodegenerative condition, which has major implications for therapy; in particular, there is a need for ongoing CNS protection in addition to controlling acute inflammatory exacerbations. Treatment of Progressive MS In an attempt to reduce relapse frequency and severity in RRMS patients, I typically employ renditions of the strategies suggested in Table 1. However, it is essential to include neuroprotective strategies in addition to a solid anti-inflammatory, relapse-oriented protocol in order to delay disease conversion to progressive MS. The following discusses a primarily theoretical approach to reducing the onset and severity of progressive MS by looking at some of the most prominent underlying mechanisms. Unfortunately, many of these have not been studied in humans with the specific end point of slowing disability progression. However, I have chosen to present the options that, in my opinion, are theoretically sound for clinical use. I will focus on four key areas that I emphasize in my practice with regards to neurodegeneration: mitochondrial dysfunction, cerebrovascular function, iron deposition, and excitotoxicity, in order to prevent the onset of or decrease the severity of progressive MS. Mitochondrial Dysfunction Mitochondrial dysfunction in MS may be mediated by the pathological opening of the mitochondrial permeability transition pore (PTP) located in the inner mitochondrial membrane. The PTP is a channel that activates and opens in response to mitochondrial stress (Su 2013). In MS, loss of myelin greatly impairs the efficiency of action potential propagation, resulting in mitochondrial dysfunction February / March 2014 l www.ihpmagazine.com 49

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and damage. The chain of events proceed: first, in response to demyelination, sodium channels become redistributed along the axon and their synthesis is upregulated. This results in increased energy requirements to maintain neuronal function. When the demand for ATP exceeds the production capabilities of existing mitochondria, the Na+/K+ ATPases begin to fail. An excess of Na+ ions accumulates within the intracellular space, and eventually this reverses the Na+/ Ca2+ exchanger that normally moves Na+ into the cell and Ca2+ from the cell. Instead, calcium accumulates within the cell. The PTP pore then opens in response to elevated

monohydrate as a nootropic agent has been demonstrated in healthy adults by supplementing with 5g per day for six weeks, resulting in improvements in working memory (backward digit span) and intelligence (Rae 2003). Creatine has also been shown to maintain the mitochondrial creatine kinase in an octameric conformation. Mitochondrial creatine kinase can exist as either a dimer or an octamer, and the enzyme’s function is determined by its structure (Adhihetty 2008). The octameric form of the mitochondrial creatine kinase interacts with components of the PTP to suppress pore opening and potentially reduce mitochondrial apoptotic

Table 1: Anti-inflammatory strategies targeting relapse severity and frequency

R+ Lipoic acid 1200mg qd (Yadav 2010) EPA/DHA 2-3g (3:2)qd (Shinto 2009, Weinstock-Guttman 2005) Vitamin D 10 000 IU with 1200mg calcium qd (Burton 2010, VanAmerongen 2004) EGCG 300mg tid (Atkas 2004) IgG (subsets 1-4) testing with gluten and dairy free diets, with dairy free probiotic (Greve 2001, Guggenmos 2004, Hadjivassiliou 2010) calcium, however persistent PTP opening leads to loss of the mitochondrial membrane potential, equilibration of ionic gradients, and promotes mitochondrial matrix swelling and outer membrane rupture (Su 2009).

Treatments that increase ATP production may prevent PTP dysfunction. We can attempt to increase ATP production with the use of creatine monohydrate. It is well known that exogenous creatine supplementation provides additional phosphocreatine, which acts as a reserve of high-energy phosphates for ATP production (Rosenfeld 2008). Creatine is taken up by the neuron via specific creatine transporters and phosphorylated to the high-energy phosphocreatine by either mitochondrial or cytosolic creatine kinases (Adhihetty 2008). Supplying exogenous creatine monohydrate can provide additional substrate for ATP production to meet the increased demand that occurs with demyelination. The activity of creatine

susceptibility (Adhihetty 2008). On the other had, upon exposure to oxidative stress, the enzyme undergoes a conformational change to the dimeric form, losing this functionality (Adhihetty 2008). A “slow load” of creatine supplementation for 28 days at a rate of 3g/day may be considered equivalent to a six day “fast load” protocol of 20g per day used in athletes, both with a 2g per day maintenance dose thereafter. Based on this I typically recommend one half teaspoon for month one, with maintenance of approximately one-third of a teaspoon. Creatine supplementation is easy and convenient as it rapidly dissolves in water and is extremely cost effective for long term use. Acetyl-L-carnitine (ALCAR) is another promising substance that enhances mitochondrial function by facilitating fatty acid transport. To enter the mitochondria, fatty acids must bind to coenzyme A, forming fatty acyl-CoA. Long-chain fatty acylCoA molecules are too large to cross the

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ve 2001,

The The Journal Journal of of IHP IHP

internal mitochondrial membrane and rely on enzymatic transportation that requires L-carnitine (NMCD Carnitine monograph). ALCAR administration results in increased intracellular levels of L-Carnitine. Both IV and oral administration of acetyl-Lcarnitine result in a corresponding increase in cerebrospinal fluid concentrations of ALCAR, indicating it readily crosses the blood-brain barrier and can facilitate delivery of additional substrate for ATP synthesis to mitochondria (Alt Med Rev 2010). ALCAR has been studied clinically in MS patients. Evidence of improved fatigue (implying improved neuronal function) was seen in 36 MS patients who were treated for three months with either amantadine (pharmaceutical for MS fatigue) or ALCAR (1g twice daily); after a three month washout period, the patients were crossed over to the opposite treatment. The authors found that 29% of patients improved after ALCAR compared to 21% after amantadine (Tomassini 2004). With regards to acute inflammation, ALCAR may also decrease reactive nitric oxide (NO) derivative species. Reactive nitric oxide derivatives are cytotoxic to oligodendrocytes and neurons in culture by inhibiting the mitochondrial respiratory chain. MS patients are known to have increased nitrosative stress, as activated glia secrete reactive nitrogen species (Bizzozero 2005). In a clinical trial, ten MS patients were treated for six months with 2g ALCAR and compared to untreated MS subjects or patients with non-inflammatory neurological conditions. Prior to treatment, concentrations of reduced glutathione were approximately 38% lower in MS patients compared to controls, implying increased baseline inflammatory activity. Treatment with ALCAR resulted in decreased CSF levels of NO reactive metabolites as well as increased content of reduced glutathione (Calabrese 2003). In my experience, the effects of ALCAR on MS fatigue are subtle, however, it is an extremely well tolerated intervention, and provides acute inflammatory as well as chronic metabolic support. A dose of 1.01.5g bid is a common recommendation.

Dosing on an empty stomach is recommended, to maximize its absorption in the jejunum (Alt Med Rev 2010). Cerebrovascular Function CCSVI (cerebrospinal venous insufficiency) is an area that MS patients often inquire about. CCSVI refers to the idea that blocked extracranial venous blood outflow causes cerebral venous reflux in MS patients. It seems now that scientific evidence supporting a causal relationship between CCSVI and MS is lacking. If MS is associated with CCSVI, it is most probably an acquired phenomenon that occurs particularly in MS patients associated with age (Lanzillo 2013). Nonetheless, in my practice I have observed substantial improvements in neurological function in some patients following CCSVI surgery, and from a non-surgical perspective, it is well known that cognition improves among non-MS patients following use of naturally occurring nootropics that improve blood flow, such as ginkgo. Ultimately, whether or not impaired blood flow is an etiological phenomenon in MS, improving cerebral circulation remains an important area of focus when addressing neurodegeneration; improved circulation results in improved oxygen and nutrient delivery to neurons experiencing increased energy demands. The two agents I use often are Ginkgo biloba and Vinpocetine.

In MS patients, ginkgo has been shown to improve both functional and cognitive parameters when dosed at 240mg per day (Johnson 2006, Lovera 2007). The Johnson study used an extract standardized to 24% flavonoid glycosides, 6% terpene lactone (2006), while the Lovera study used an extract standardized to 31.4% flavonoids, 4.5 % terpenes (2007). Neuroprotective effects of ginkgo have been demonstrated in several in vitro and in vivo models, specifically showing protection of cultured neurons against death induced by hypoxia, glutamate and nitric oxide (Ahlemeyer 2003). Ginkgo also appears to have IL-6 lowering ability when given to patients with age-related neurological disorders (Ching-Hsiang 2012). Interestingly, ginkgo appears to be able to increase endothelial nitric oxide synthase (eNOS) mediated NO production, resulting in vasodilation, whereas it inhibits inducible NOS (iNOS) mediated

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NO production, thereby preventing excessive NO synthesis by macrophages (Ahlemeyer 2003). This suggests that Ginkgo may reduce acute inflammation while providing increased blood flow to damaged neurons. My preference has been to dose Ginkgo at 120mg bid (standardized to 24% and 6%) because it’s readily available at this standardization, and reflects the dose used in Johnson (2006). Vinpocetine is an interesting substance due to its ability to increase blood flow, as well as its therapeutic potential in neurogenic bladder. In one study, intravenous vinpocetine increased both global and regional cerebral blood flow, with 36% and 37% increases in blood flow to the thalamus and caudate nucleus respectively, as measured by positron emission tomography (PET) (Szilágyi 2005). An oral dosing study using PET imaging also demonstrated increased cerebral blood flow as well as improvements in cognition in patients with mild cognitive impairment due to cerebral hypoperfusion (Valikovics 2007). Vinpocetine has also been studied for bladder dysfunction. In a pilot study of 19 patients with urge incontinence, sensory incontinence and low compliance bladders, three patients reported slight improvement, and eight reported pronounced improvement within four weeks (Truss 2000). MS patients with neurogenic bladder are considered motor urge incontinent (overactive detrusor). A larger follow up trial in a “worst case scenario population” with primarily detrusor instability showed less pronounced benefits (Truss 2001). Both the vascular and bladder related improvements are attributed to vinpocetine’s phosphodiesterase-1 inhibitory activity. Viagra is a pharmaceutical phosphodiesterase-5 inhibitor (Truss 2001). Phosphodiesterase inhibitors (PDEIs) suppress TNF-alpha production by various cells and suppress experimental demyelination. In a pilot study of 12 MS patients, a combination of three PDEIs was shown to reduce annual relapse rates (Suzumura 2000). Under fasting conditions, vinpocetine has about 7% bioavailability so it must be given with food (Paytar 2011). I typically dose 45mg per day, however 30-60mg is suggested by a 2003 Cochrane review as being suitable for cognitive impairment (Szatmari 2003). Emprical use of vinpocetine for bladder

function should be for at least one month, as results were seen within one month in the study by Truss (2000). Precautions related to risk of bleeding relate to both ginkgo and vinpocetine (NMCD Vinpocetine monograph). Iron Deposition Zamboni’s CCSVI theory proposed that venous reflux leads to iron deposition, inflammation and leukocyte infiltration. Regardless of whether the CCSVI hypothesis is correct, iron is in fact implicated in a number of neurodegenerative diseases and senile dementia since it accumulates in the brain with age, and ionic iron can in turn participate in the Fenton reaction with subsequent generation of ROS, initiating the processes of oxidative stress (Singh 2009, Weinreb 2009). In one study, the brain tissue of 33 MS and 30 control cases were analyzed. In active MS lesions, iron was apparently released from dying oligodendrocytes, resulting in extracellular accumulation of iron and it was suggested that cellular degeneration in MS lesions leads to waves of iron liberation, which may further propagate neurodegeneration (Hametner 2013). In mice being fed oral EGCG, a human equivalent dose of three litres of green tea, dramatically suppressed experimental autoimmune encephalomyelitis (EAE, the animal model of MS) (Atkas 2004). EGCG inhibits Th1 and Th17 differentiation, NF-kb, and ROS, making it one of my top choices for use in reducing relapse severity and frequency (Wu 2012). However, in the context of neurodegeneration, EGCG can also chelate ionic iron to form inactive complexes (Weinreb 2009). Interestingly, a recent study has shown invivo synergy of EGCG and copaxone (daily injectable immune-modulating MS treatment) in EAE, and the authors encouraged the combination of anti-inflammatory and neuroprotective treatments (Herges 2011). Converting the mouse EGCG dose (300 ug bid) used in the first EAE study to an equivalent human dose (assuming 60kg human and 20g mouse) yields approximately 1459mg EGCG as the therapeutic human dose (Mouse-Genome 2010, Reagan-Shaw 2008). Although there are many factors to be considered in extrapolating animal dosages and their effects to humans, this study does

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provide a loose estimate. In practice, I dose EGCG at about 900mg per day when trying to reduce relapse frequency or as an adjuct to interferon, since dosing of EGCG alone at 800mg is a dose that has consistently been shown to be safe in a human pharmacokinetic study. There have been case reports of hepatotoxicity with EGCG, which suggest some caution should be used with higher dosages. The other catechins present in green tea extract possess similar properties to EGCG, and can be used to help make up the full catechin dose used in the EAE study (Chow 2003, Shanafelt 2009). In terms of using EGCG to prevent neurodegeneration, I encourage, at the very least, daily ad libitum consumption of green tea beverage to ensure some degree of iron chelation as part of their neuroprotective regime. Excitotoxicity Evidence has accumulated that excessive glutamate is released at the sites of demyelination and axonal degeneration in MS plaques, and the most probable candidates for this cellular release are infiltrating

agonist, and I have seen good effects in MS spasticity with this approach (Held 2002). I always combine calcium with vitamin D prescription. As mentioned in Table 1, I often recommend 10,000 IU of vitamin D daily in MS. Studies of EAE and a 2010 human dose escalation study where doses reached 40 000 IU indicate that the immune modulatory actions of vitamin D may be contingent on concomitant calcium administration (approximately 1200mg) (Burton 2010, VanAmerongen 2004). As a result, I regularly suggest 10,000 IU vitamin D, 1200mg calcium, and 600mg magnesium nightly. The anxiolytics GABA and taurine can also be considered, especially if anxiety is part of the symptomatology, since taurine is a GABA agonist and may have independent neuroprotective effects, while GABA promotes specific patterns of brain activity (Abdou 2006, Oja 2007). Lastly, as a foundation for more advanced supplement therapies, B-vitamins and a diet including daily berry consumption are often prescribed for general cognitive

Table 2: Proposed Strategies for Progressive MS (Neurodegeneration) Creatine Monohydrate: Slow Load 3g for 1 month, followed by 2g maintenance.

Acetyl-L-Carnitine: 1 â&#x20AC;&#x201C; 1.5g bid on empty stomach preferably Ginkgo biloba: 120mg bid Vinpocetine: 15-30mg bid (must be dosed with food) EGCG: daily consumption Magnesium: 600mg as an adjunct to calcium and vitamin D Methylated B complex with benfotiamine Â

leukocytes and activated microglia (Frigo 2012). One study looking at MS patients compared to healthy patients, found the presence of elevated glutamate in active lesions using 3D MRI. One of the primary glutamate receptors, the NMDA receptor, allows the influx of cations, though most notably calcium. Excessive glutamate stimulation causes excessive intracellular calcium accumulation, leading to excitotoxic injury (Lau 2010). One study looked at 16 patients with MS, where one year without treatment was followed by 1-year riluzole (inhibits glutamate release from neurons). Treatment resulted in reduced spinal atrophy and reduced T1 lesions (active lesions) (Killestein 2005). Although pharmacologic glutamate inhibitors are not currently being employed for this, we can use natural glutamate antagonists to combat the excitotoxicity. GABA receptors provide a counterbalance to glutamate receptors (Rossi 2012). My preference is to use daily magnesium as an adjunct to calcium supplementation; magnesium is a NMDA antagonist and GABA-A

function. A B complex with methylated B12 and benfotiamine is preferred for homocysteine reduction and optimal nerve transmission. Lower median CSF vitamin B12 concentrations were found in groups of patients with MS and serum homocysteine is significantly increased in MS patients (Niist 1990, Vrethem 2003). Blueberry consumption has been shown to improve memory in older adults, has been shown to improve blood brain barrier integrity, and can suppress NF-kb by about 27% in humans when used at a dose of 200g daily (Karlsen 2007, Krikorian 2010, Robert 1977). Promising prospective therapies that I may add to my formulary in future include: low dose lithium orotate, pyrroloquinoline quinone (PQQ), and Centella asiatica for their effects on brain derived neurotrophic factor (BDNF), nerve growth factor (NGF) and nerve regeneration respectively (Misra 2012, Rowe 2004, Soumyanath 2005). I look forward to more research emerging on the possible role of these agents. February / March 2014 l www.ihpmagazine.com 53

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In conclusion, MS should be treated as both an inflammatory and neurodegenerative condition. RRMS patients need neuroprotective support immediately, alongside their immune modulatory therapies because the onset of progressive varies greatly and can even be immediate (primary progressive). It is my opinion that neuroprotective strategies addressing mitochondrial dysfunction, iron deposition, excitotoxicity, and vascular perfusion in addition to anti-inflammatory treatments are a well rounded approach to reducing the possibility and severity of progressive disability accrual. References Abdou AM. Biofactors. 2006;26(3):201-8. Adhihetty PJ. Neuromolecular Med. 2008;10(4): 275-90 Ahlemeyer B. Cell Mol Life Sci. 2003 Sep;60(9):1779-92. Aktas O. J Immunol. 2004 Nov 1;173(9):5794-800 Alt Med Rev. Altern Med Rev. 2010 Apr;15(1): 76-83. Bizzozero OA. Neurochem Res. 2005 Jan;30(1): 139-49. Burton JM. Neurology. 2010 Jun 8;74(23):1852-9. Calabrese V. Neurochem Res. 2003 Sep;28(9): 1321-8. Chow HH. Clin Cancer Res. 2003 Aug 15;9(9):3312-9. Ching-Hsiang L. Indian J Pharmacol. 2012 Jan;44(1):118-21. Frigo M. Curr Med Chem. 2012;19(9):1295-9. Gelinas DF. Amyotroph Lateral Scler. 2008 Oct;9(5):266-72. Greve B. J Neuroimmunol. 2001 Dec 3;121(12):120-5. Guggenmos J. J Immunol. 2004 Jan 1;172(1):661-8. Hadjivassiliou M. Lancet Neurol. 2010 Mar;9(3):318-30. Hametner S. Ann Neurol. 2013 Jul 19. Held K. Pharmacopsychiatry. 2002 Jul;35(4):135-43. Herges K. PLoS One. 2011;6(10):e25456. Johnson SK. Explore (NY). 2006 Jan;2(1):19-24. Karlsen A. J Nutr. 2007 Aug;137(8):1951-4 Killestein J. J Neurol Sci. 2005 Jun 15;233(1-2): 113-5. Korn T. J Neurol. 2008 Dec;255 Suppl 6:2-6. Krikorian R. 2010 Apr 14;58(7):3996-4000. Lau A. Pflugers Arch. 2010 Jul;460(2):525-42. Lanzillo R. BMC Neurol. 2013 Feb 13;13:20. Luessi F. Expert Rev Neurother. 2012 Sep;12(9):1061-76. Lovera J. Mult Scler. 2007 Apr;13(3):376-85.

Mashayekh A. Neuroradiology. 2011 Mar;53(3):185-91. Misra HS. J Biosci. 2012 Jun;37(2):313-25. Mouse Genome Informatics. Accessed May 2 2010. Nijst TQ. J Neurol Neurosurg Psychiatry. 1990 Nov;53(11):951-4. NMCD Acetyl-L-Carnitine Monograph. Natural Medicines Comprehensive Database. Accessed online September 2013. NMCD Vincpocetine Monograph. Natural Medicines Comprehensive Database. Accessed online September 2013. Oja SS. Proc West Pharmacol Soc. 2007;50:8-15. Rae C. Proc Biol Sci. 2003 Oct 22;270(1529): 2147-50. Rahn KA. Curr Med Chem. 2012;19(9):1335-45. Reagan-Shaw S. FASEB J. 2008 Mar;22(3): 659-61. Robert AM. J Med. 1977;8(5):321-32. Rosenfeld J. Expert Rev Mol Med. 2004 Oct 18;6(21):1-18. Rossi S. Mult Scler. 2012 Nov;18(11):1633-5. Santos RF. Pharmacopsychiatry. 2003 Jul;36(4): 127-33. Scalfari A. J Neurol Neurosurg Psychiatry. 2013 Mar 13. Shanafelt TD. J Clin Oncol. 2009 Aug 10;27(23):3808-14. Shinto L. Prostaglandins Leukot Essent Fatty Acids. 2009 Feb-Mar;80(2-3):131-6. Singh AV. J Cereb Blood Flow Metab. 2009 Dec;29(12):1867-78. Soumyanath A. J Pharm Pharmacol. 2005 Sep;57(9):1221-9. Suzumura A. Mult Scler. 2000 Feb;6(1):56-8. Su KG. Curr Neurol Neurosci Rep. 2009 Sep;9(5):411-7. Su K. Front Physiol. 2013;4:169. Szilรกgyi G. J Neurol Sci. 2005 Mar 15;229230:275-84. Szatmari SZ. Cochrane Database Syst Rev. 2003;(1):CD003119. Tomassini V. J Neurol Sci. 2004 Mar 15;218 (1-2):103-8 Truss MC. World J Urol. 2001 Nov;19(5):344-50. Truss MC. World J Urol. 2000 Dec;18(6):439-43. Valikovics A. Ideggyogy Sz. 2007 Jul 30;60(78):301-10. VanAmerongen BM. Eur J Clin Nutr. 2004 Aug;58(8):1095-109. Vrethem M. Mult Scler. 2003 Jun;9(3):239-45. Weinreb O. Genes Nutr. 2009 Dec;4(4):283-96. Weinstock-Guttman B. Mol Aspects Med. 2012 Feb;33(1):107-18. Yadav V. Mult Scler. 2010 Apr;16(4):387-97.

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Eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) are for their anti-inflammatory effects, exerted through competitive inhibition of the cyclooxygenase (COX-2) and lipooxygenase (LOX) enzymes (Lim 2009); and have been the subject of extensive scientific research for their benefit on brain and cognitive function, cardiovascular health, as well as a broad range of inflammatory conditions such as arthritis, inflammatory bowel disease (IBD), and liver disease (Wall 2010). With respect to cognitive function, supplementation with EPA and DHA has been shown to improve cerebral circulation, improve mood, and various measures of cognitive function including language and orientation skills. In an imaging study, supplementation with 1g DHA was shown to increase cerebral blood flow and oxygenation during cognitive tasks (Jackson 2012). In an RCT, supplementation with approximately 2g EPA and DHA over six months was shown to improve patients’ scores on the Geriatric Depression Scale (GDS), verbal fluency, and self-reported physical health compared to supplementation with linoleic acid (n-6) alone in patients with mild cognitive impairment (MCI) (Sinn 2012). Another study found that while supplementation with low dose EPA/ DHA (600mg) in addition to B-vitamins for four years showed no effect overall with respect to cognitive function in a group of over 1700 patients with established cardiovascular disease (heart attack, stroke, etc), there was a significant effect among patients with a previous history of stroke (Andreeva 2011). These patients were significantly less likely to have a decreased score on the temporal orientation task compared to placebo (OR 0.43, 95% CI 0.21-0.86). It is possible that with a higher dose, more generalized benefit may have been demonstrable. In addition to cognitive health, fish oil has been reproducibly demonstrated to reduce the risk of sudden coronary death, as well as nonfatal cardiac events with a large magnitude of effect, in both patients recovering from a heart attack (secondary prevention) and in patients with no history of cardiovascular events (primary prevention) (Marchioli 2002, Yokoyama 2007). The Gissi Prevenzione trial, conducted in over 11 thousand patients, found that 1000mg daily of combined EPA+DHA for 3.5 years in addition to standard pharmaceutical therapy reduced the risk of sudden coronary death by 45% (RR 0.55, 95%CI 0.39–0.77), and reduced risk of all cause death by 21% (RR 0.79, 95%CI 0.66–0.93) (No authors 1999, Marchioli 2002). EPA+DHA have also been shown to benefit cholesterol; however, larger doses are required. A dose of 2000 to 4000mg of combined EPA+DHA reduces fasting TG 25-30% and increases HDL cholesterol 1-3% (Harris 1997). A dose of 2tsp of MedOmega Fish Oil easily achieves this dose. Through this anti-hyperlipidemia mechanism, higher doses of fish oil yield added benefits to cardiovascular health. EPA has also been shown to reduce the inflammatory activity of atherosclerotic plaques when incorporated into these arterial lesions, thus slowing their progression (Cawood 2010). Carlson guarantees the quality and potency of their fish oil. MedOmega is regularly subjected to rigorous independent testing by an FDA-registered laboratory for the mercury, cadmium, lead, PCBs, and 28 other contaminants. Carlson fish oil is bottled in Norway to provide maximum purity and product freshness. References Andreeva VA, Kesse-Guyot E, Barberger-Gateau P, Fezeu L, Hercberg S, Galan P. Cognitive function after supplementation with B vitamins and long-chain omega-3 fatty acids: ancillary findings from the SU.FOL.OM3 randomized trial. Am J Clin Nutr. 2011 Jul;94(1):278-86. Cawood AL, Ding R, Napper FL, Young RH, Williams JA, Ward MJ, Gudmundsen O, Vige R, Payne SP, Ye S, Shearman CP, Gallagher PJ, Grimble RF, Calder PC. Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability. Atherosclerosis. 2010 Sep;212(1):252-9. Gruenwald J, Petzold E, Busch R, Petzold HP, Graubaum HJ. Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis. Adv Ther. 2009 Sep;26(9):858-71. Harris WS. n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997 May;65(5 Suppl):1645S-1654S. Jackson PA, Reay JL, Scholey AB, Kennedy DO. DHA-rich oil modulates the cerebral haemodynamic response to cognitive tasks in healthy young adults: a near IR spectroscopy pilot study. Br J Nutr. 2012 Apr;107(8):1093-8. Lim K, Han C, Dai Y, Shen M, Wu T. Omega-3 polyunsaturated fatty acids inhibit hepatocellular carcinoma cell growth through blocking beta-catenin and cyclooxygenase2. Mol Cancer Ther. 2009 Nov;8(11):3046-55. Marchioli R, Barzi F, Bomba E, et al; GISSI-Prevenzione Investigators. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation. 2002 Apr 23;105(16):1897-903. Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA. 2006 Oct 18;296(15):1885-99. No Authors. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet. 1999 Aug 7;354(9177):447-55. Sinn N, Milte CM, Street SJ, Buckley JD, Coates AM, Petkov J, Howe PR. Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial. Br J Nutr. 2012 Jun;107(11):1682-93. Wall R, Ross RP, Fitzgerald GF, Stanton C. Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev. 2010 May;68(5):280-9. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007 Mar 31;369(9567):1090-8.

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Essential Hypertension Management Considerations By Elaine Lewis, ND Elaine Lewis, ND Research Resident, Canadian College of Naturopathic Medicine 1255 Sheppard Avenue East North York, Ontario Back To Play Chiropractic , 592 Rathburn Road West, Mississauga, On L5B 3A4 elewis@ccnm.edu

Abstract Over six million Canadians are currently affected by hypertension, a primary risk factor for cardiovascular disease. Elevated blood pressure accounts for approximately 13% of all deaths. The Canadian Hypertension Education Program (CHEP) provides annual recommendations for the assessment and management of hypertension in Canada. This article reviews the 2013 CHEP recommendations with a view to their application by integrative healthcare practitioners. For in-office diagnosis of hypertension, if blood pressure is elevated (SBP ≥140 mmHg and/or DBP ≥90 mmHg), it should be re-measured twice more in the same visit. The first measurement should be discarded and the latter two averaged to determine blood pressure. A focused physical exam and history assessing for target organ damage and cardiovascular risk should be performed; and a second visit should be conducted within a month to re-assess blood pressure. Special considerations exist for patients with diabetes and the very elderly. Target blood pressure in diabetics is SBP ≤130 mmHg and DBP ≤80 mmHg; while in patients ≥ 80 years of age it is SBP ≤150 mmHg. The role of integrative medicine in managing hypertension is discussed.

Introduction Hypertension continues to be the primary risk factor for cardiovascular disease development, leading to myocardial infarction, congestive heart failure, stroke and kidney disease (Chobanian 2003). Worldwide, elevated blood pressure is also the leading risk factor for all cause mortality, accounting for 13% of all deaths (Robitaille 2012). The Framingham Heart Study data suggests that adults who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension (Vasan 2002), a statistic that warrants considerable emphasis on preventative cardiovascular efforts. The Canadian prevalence of hypertension is growing yearly, with six million diagnosed in 2008; hypertension is most prevalent in Atlantic

Canada. Prevalence increases with age and in the female gender (after the sixth decade of life) (Robitaille 2012). The Canadian Hypertension Education Program (CHEP), operated and funded by Hypertension Canada, provides yearly updates to its recommendations for hypertension assessment and managementin Canada, a feat unmatched by any other country’s task force for hypertension or cardiovascular disease to date. An evidence-based approach is undertaken on an annual basis via systematic review of relevant clinical literature and recommendations are developed and disseminated by key independent stakeholders without external influence. The 2013 CHEP guidelines incorporate new recommendations for February / March 2014 l www.ihpmagazine.com 57

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special populations suffering with hypertension as well as a greater emphasis on lifestyle and dietary considerations for management (Hackam 2013). These updates are relevant to integrative and conventional practices alike, and provide a more notably holistic approach to hypertension care. This paper will review current Canadian recommendations for blood pressure assessment and management with special attention to the integrative healthcare practitioner’s role in providing best patient care. Hypertension diagnosis A diagnosis of elevated blood pressure, either in-office or by patient self-report, requires a specific workup based on certain criteria. In order to confirm a diagnosis

to determine visit 1 blood pressure. b. Schedule follow-up within 1 month for assessment of hypertension. c. Conduct a focused history and physical examination to assess cardiovascular disease risk and target organ damage (TOD) (defined in Table 2). d. Assess for contributing exogenous factors and secondary causes of hypertension. Visit 2: Follow-up assessment 1. If SBP ≥140 mmHg and/or DBP ≥90 mmHg with macrovascular target organ damage (TOD), diabetes mellitus (DM) or chronic kidney disease (CKD), diagnose hypertension. 2. If SBP ≥180 mmHg and/or DBP ≥110

Figure 1. CHEP 2013 Algorithm for the Assessment of Patients with Hypertension (Hackam 2013)

hypertension, an algorithm for blood pressure measurement has been created by CHEP 2013, as outlined in Figure 1. Visit 1: Initial assessment 1. If the initial blood pressure denotes hypertensive urgency or emergency (defined in Table 1), an immediate diagnosis of hypertension is made and treatment is initiated. 2. If blood pressure is elevated (SBP ≥140 mmHg and/or DBP ≥90 mmHg): a. Re-measure twice more in the same visit. The first measurement is discarded and the latter two averaged

mmHg without macrovascular TOD, DM or CKD, diagnose hypertension. Visits 3-5: Follow-up assessment 1. If SBP ≥160 mmHg and/or DBP ≥100 mmHg averaged across first 3 visits, diagnose hypertension. 2. If SBP ≥140 mmHg and/or DBP ≥90 mmHg averaged across first 5 visits, diagnose hypertension. 3. If at the last visit the patient does not meet diagnostic criteria, and has no macrovascular TOD, reassess blood pressure yearly.

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Table 1. Recognize Hypertensive Urgencies and Emergencies (Hackam 2013) 1. Asymptomatic diastole ≥ 130 mmHg 2. Elevations of blood pressure with: • Hypertensive encephalopathy • Acute aortic dissection • Acute left ventricular failure • Acute coronary syndrome • Acute kidney injury • Intracranial hemorrhage • Acute ischemic stroke • Eclampsia of pregnancy Table 2. Target Organ Damage Examples (Hackam 2013) 1. Cerebrovascular Disease a. Stroke: ischemia, transient ischemic attack, intracerebral hemorrhage, sub-arachnoid hemorrhage b. Dementia: vascular, mixed vascular, Alzheimer’s 2. Hypertensive Retinopathy 3. Left Ventricular Dysfunction 4. Coronary Artery Disease a. Myocardial infarction b. Angina pectoris c. Congestive heart failure 5. Renal Disease a. Chronic kidney disease b. Albuminuria 6. Peripheral Artery Disease a. Intermittent claudication In addition to these general guidelines for hypertension assessment and diagnosis, considerations must be made for certain special populations as defined by CHEP. These groups may not be best addressed by the general recommendations listed above due to physiological and/or clinical differences that affect blood pressure. When patients fall into these groups or subpopulations, it is important to adopt the specific guidelines relating to the implicated subpopulation in order to improve outcomes. Hypertension and Diabetes The prevalence of hypertension in diabetic patients is 63%, with 60-80% of diabetics dying from cardiovascular complications largely attributable to hypertension (Campbell 2009). Given the elevated risk of cardiovascular events in diabetics with comorbid hypertension, it is especially important for healthcare practitioners to be aware of their specific blood pressure targets

and requirements. Integrative practitioners are specially poised to effectively address this group, given their expertise and ability to provide guidance on dietary and lifestyle modifications that help diminish this risk. New 2013 recommendations for target blood pressure in diabetics are SBP ≤130 mmHg and DBP ≤80 mmHg (Hackam 2013). This target is based on evidence suggesting that more adverse events and less cardiovascular risk reduction is noted in intensive therapy where SBP targets were ≤120 mmHg vs. standard therapy using SBP targets ≤140 mmHg. Given that diabetics have well-known problems relating to hypoperfusion, pushing blood pressure too low with treatments may also exacerbate events such as hypotension, syncope, bradycardia, hyperkalemia, angioedema and renal failure, some of which were noted when intensive hypotensive therapy was initiated in this population (ACCORD Study Group 2010).

Hypertension in the Elderly The new recommendation for isolated systolic hypertension in the very elderly (age 80 years or older) is a target SBP ≤150 mmHg. Arterial thickening is known to occur with increasing age leading to a decrease in vessel elasticity. This physiological process results in systolic elevation with age, a finding that is now being recognized by CHEP guidelines in order to deter overmedication in the elderly population. No changes have been made to the diastolic blood pressure targets, which remain to be recommended ≤90 mmHg (Hackam 2013). American guidelines note that these patients are more likely to have white coat hypertension and isolated systolic hypertension; in order to address these instances, practitioners should measure seated blood pressure and average two or more readings per visit (Pickering 2005). Additional strategies to circumvent white coat hypertension may include relaxation techniques applied at the discretion of the provider to aid measurement accuracy. Alternate methods for measurement, such as ambulatory and home BP measures, should also be considered. Laboratory and Diagnostic Tests for Hypertensive Patients Upon diagnosis of hypertension, the routine investigational laboratory panel should include the following: February / March 2014 l www.ihpmagazine.com 59

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1) Urinalysis* 2) Blood chemistry (potassium, sodium & creatinine) 3) Fasting blood glucose 4) Fasting lipid panel (total cholesterol, HDL, LDL & triglycerides) 5) 12-lead electrocardiogram *Hypertensive patients with diabetes mellitus should also have urinary albumin assessed (Hackam 2013). These laboratory measures aid in the investigation of target organ damage from longstanding untreated or inadequately controlled hypertension. Hypertension treatment considerations New CHEP guidelines are considerably more holistic in nature compared to previous Canadian guidelines (Daskalopoulou 2012) and currently adopted American guidelines from 2003 (Chobanian 2003). The primary focus of treatment continues to be on healthy behaviour management, including emphasis on physical exercise, weight reduction, alcohol consumption, dietary improvements, and stress management (Hackam 2013). Pharmacological drug therapy guidelines have also been amended to address the greater shift towards lifestyle modification. The most notable of these changes include the delay of antihypertensive drug initiation for patients who do not have evidence of macrovascular target organ damage or other cardiovascular risk factors. In these otherwise healthy individuals, drug therapy is not recommended until the patientâ&#x20AC;&#x2122;s blood pressure indicates stage II hypertension, with an average SBP â&#x2030;Ľ160 mmHg or DBP â&#x2030;Ľ100 mmHg (Hackam 2013). American guidelines continue to recommend drug therapy initiation for stage 1 hypertensive patients, regardless of cardiovascular risk (Chobanian 2003). In the 2013 CHEP guidelines, stage I hypertension patients are to be recommended lifestyle modification instead. The debate continues regarding which component of blood pressure is more concerning from the perspective of absolute cardiovascular risk. Recent reviews of evidence point to elevations in systolic pressure and pulse pressure as being most predictive of cardiovascular risk, whereas past epidemiological evidence has typically implicated diastolic elevation as a primary target for antihypertensive treatments

(Pickering 2000, Strandberg 2003). Diastolic elevation has historically been regarded as more concerning due to the focus of large clinical trials on diastolic pressure; however more recent studies, including the Framingham Heart Study, confirm that systolic pressure accurately predicts true hypertension 96% of time compared to diastolic readings (LloydJones 1999). Both Canadian and American hypertension guidelines fail to explicitly distinguish isolated diastolic hypertension from isolated systolic hypertension in their recommendations for assessment, though practitioners should be aware that these do exist. From an evidence perspective, isolated systolic hypertension is a greater concern and requires more aggressive antihypertensive treatments compared to isolated diastolic hypertension. Both of these phenomena are more prevalent in younger patients, often males (Pickering 2000, Pickering 2005). Lifestyle Recommendations for Hypertension First line emphasis of treatment for stage 1 hypertension and pre-hypertension includes aerobic exercise and resistance training, neither of which are considered to adversely influence blood pressure. An effort to reduce the contribution of stress to blood pressure and to maintain a normal body weight is also emphasized; an area that integrative practitioners are especially poised to address effectively (Hackam 2013). Dietary Recommendations for Hypertension Specific dietary considerations of emphasis for hypertensive patients include sodium restriction <1500 mg for patients under 50 years of age, <1300 mg for those 51-70 years, and <1200 mg for those over 70 years. Alcohol intake should also be moderated in both pre-hypertensive and hypertensive patients, with recommendations for <14 standard weekly drinks in men and <9 standard weekly drinks in women (Hackam 2013). Both of these specific dietary guidelines should be made in conjunction with the recommendation to adhere to the Dietary Approaches to Stop Hypertension (DASH) diet (Appel 2005; Hackam 2013). The DASH diet and Mediterranean diet continue to fare best at reducing absolute cardiovascular risk according to long-term and large-scale clinical trials (Appel 2005, Kokkinos 2005).

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Role of Integrative Medicine The role of an integrative medical practitioner in hypertension assessment and management is variable and diverse. Recent unpublished data reviewing naturopathic management of hypertension in a teaching clinic at the Canadian College of Naturopathic Medicine in North York, Ontario, suggests that a large proportion of practitioners fail to address their patients’ hypertension. The main reason for this trend was patient preference for a focus on other health needs given that their hypertension was being addressed by anti-hypertensive medications and followed by another health professional. Integrative practitioners are often presented with the clinical decision regarding the role played for hypertension management, specifically whether or not to adopt a primary care function in their patient’s hypertension care. The above considerations are most relevant to a primary care approach to hypertension management, though aspects of these recommendations should be incorporated into any integrative practitioner’s care. Particular emphasis is warranted with respect to special populations of hypertensive patients, such as the elderly, those with diabetes, those with target organ damage and/ or other cardiovascular risk factors, as well as otherwise healthy individuals whose drug therapy may be safely delayed. Many primary and supportive therapies are available for hypertension management whether or not a patient’s blood pressure is medicated or controlled. Knowledge of primary practice guidelines, such as those positioned by CHEP 2013 in Canada (Hackam 2013) and NHBPEP 2003 in America (Chobanian 2003), is crucial to the appropriate care of patients who suffer from hypertension and to the ultimate success of integrative approaches for cardiovascular management. Take Home Message for the Integrative Practitioner • Measure blood pressure regularly in adult patients to assess cardiovascular risk • Use a validated sphygmomanometer, choose an appropriate cuff size, and position the patient for accurate reading • Understand CHEP recommendations for patients, including special populations with unique blood pressure targets • Regularly assess for target organ damage References ACCORD Study Group, Cushman W, Evans G, Byington R, Goff D, Grimm R et al. Effects of intensive bloodpressure control in type 2 diabetes mellitus. New England Journal of Medicine. 2010; 362(17): 1575–1585. Appel L. Dietary Approaches to Prevent and Treat

Hypertension: A Scientific Statement From the American Heart Association. Hypertension. 2005; 47(2): 296–308. Campbell N, Leiter L, Larochelle P, Tobe S, Chockalingam A, Ward R et al. Hypertension in diabetes: a call to action. Canadian Journal of Cardiology. 2009; 25(5): 299–302. Chobanian A, Bakris G, Black H, Cushman W, Green L, Izzo J et al. Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003; 42(6): 1206–1252. Daskalopoulou S, Khan N, Quinn R, Ruzicka M, McKay D, Hackam D et al. Canadian Journal of Cardiology. 2010; 28(3): 270–287. Hackam D et al. The 2013 Canadian Hypertension Education Program Recommendations for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension. Canadian Journal of Cardiology. 2013; 29(5): 528–542. Kokkinos P, Panagiotakos D, Polychronopoulos E. Dietary influences on blood pressure: the effect of the Mediterranean diet on the prevalence of hypertension. Journal of clinical hypertension. 2005; 7(3): 165–70.

Lloyd-Jones D, Evans J, Larson M, O’Donnell C, Levy D. Differential Impact of Systolic and Diastolic Blood Pressure Level on JNC-VI Staging. Hypertension. 1999; 34(3): 381–385. Pickering T. Effects of Stress and Behavioral Interventions in hypertension - Headache and Hypertension: Something Old, Something New. Journal of clinical hypertension. 2010; 2(5): 345–347. Pickering T. Recommendations for Blood Pressure Measurement in Humans and Experimental Animals: Part 1: Blood Pressure Measurement in Humans: A Statement for Professionals From the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Circulation. 2005; 111(5): 697–716. Robitaille C, Dai S, Waters C, Loukine L, Bancej C, Quach S et al. Diagnosed hypertension in Canada: incidence, prevalence and associated mortality. Canadian Medical Association Journal. 2012; 184(1): E49–E56. Strandberg T, Pitkala K. What is the most important component of blood pressure: systolic, diastolic or pulse pressure? Current opinion in nephrology and hypertension. 2003; 12(3): 293–297. Vasan R, Beiser A, Seshadri S, Larson M, Kannel W, D’Agostino R, Levy D. Residual lifetime risk for developing hypertension in middle-aged women and men. The Journal of the American Medical Association. 2002; 287(8): 1003–1010. February / March 2014 l www.ihpmagazine.com 61

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

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

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

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

(100 Billion bacteria)

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

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

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

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

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

Chol SAP-15 Science-based phytosterols formulated in flaxseed oil to ensure efficacy Phytosterols are plant analogs of cholesterol which lower blood cholesterol levels, thus reducing the risk of cardiovascular disease (CVD). Evidence shows that LDL-cholesterol and total cholesterol concentrations can be decreased between 8 and 15% with intakes of phytosterols of 1.05 g/d. Additional available data hint at a possible action of phytosterols in improvement of resistance to some carcinogens.

ACTIVE INGREDIENTS

Each softgel contains:

Total sterols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350 mg beta-Sitosterols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151.2 mg Stigmasterols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84.4 mg Campesterols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60.1 mg delta-5-Avenastenols. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.7 mg delta-5.24-Estigmastenols . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 mg delta-7-Estigmastenols. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.8 mg delta-Avenastenols. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.7 mg Plus Certified organic flax seed oil . . . . . . . . . . . . . . . . . . . . . . . . . . 666 mg Made from vegetable source: Helianthus annuus (sunflower) (seed) and/or Soja hispida (soy) (bean). Contains no: Preservatives, artificial flavor or color, sugar, dairy, wheat, gluten, corn or yeast. Chol SAP‑15 (phytosterols) contains 120 softgels per bottle.

DOSAGE

Adults: Take 3 softgels daily with food or as directed by your health care practitioner. 3 softgels provide 1.05 g phytosterols plus up to 1 g alpha-linolenic acid (omega-3 fatty acid).

INDICATIONS

ɶ Independent use of Chol SAP‑15 twice daily with meals will reduce serum LDL-cholesterol up to 15% and total cholesterol up to 12%. ɶ Use of Chol SAP‑15 twice daily with meals in addition to a low-fat diet may reduce serum total and LDL-cholesterol up to 25%.

FORM TO GUARANTEE EFFICACY

ɶ Phytosterols are lipophilic, thus for optimal absorption and efficacy, phytosterols must be dissolved in a lipid base, such as the organic flax seed oil base used in Chol SAP‑15. ɶ The phytosterols supplied in Chol SAP‑15 are in a natural non-esterified and nonsaturated form, thus avoiding excess processing and chemical hydrogenation.

PURITY, CLEANLINESS AND STABILITY

Third-party testing is performed on finished product to ensure Chol SAP‑15 is free of heavy metals, pesticides, volatile organics and other impurities.

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

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

IHP 2014-02 (Chol SAP).indd 1 IHPAPR2012_XXXX_ADVERTISER_Product_FP.indd 1

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The Journal of IHP

Demystifying Bioidentical Hormones A Review Of BHRT Use In Clinical Practice With Respect To Menopausal Concerns By Tannaz Mokhtari, BSc, ND and Ishita Patel, HBSc, Pharm D, RPh Tannaz Mokhtari, BSc, ND and Ishita Patel, HBSc, Pharm D, RPh Hayyan HealthCare , 9301 Bathurst St. Unit 8, Richmond Hill, On L4C 3T7 tannaz@yournd.com

Abstract This article provides an overview of the scientific literature regarding the safety and efficacy of bioidentical hormone replacement therapy (BHRT) for the treatment of symptoms associated with menopause, including vasomotor symptoms, urinary tract infections, and vaginal atrophy. This review specifically compares safety of bioidentical estrogens and progesterone to conventional hormone replacement therapy (HRT). Data from large randomized controlled trials such as the Womenâ&#x20AC;&#x2122;s Health Initiative (WHI) and the Heart and Estrogen/progestin Replacement Study (HERS) demonstrate detrimental effects resulting from use of estrogen in combination with synthetic progestins. In contrast, data from the large E3N cohort suggest that bioidentical progesterone may offset this risk. Progesterone differs from synthetic progestins in its biological effects on breast tissue, metabolic parameters, as well as on the cardiovascular system. In addition, different routes of BHRT delivery will be discussed, comparing topical and transdermal application methods with oral administration.

Introduction Bioidentical hormones are manufactured to be molecularly identical to endogenous human hormones. They are derived primarily from plant sources, such as soy and wild Mexican yam root. The extracted plant compounds then undergo synthetic processing to obtain structures identical to endogenous human

hormones (Bosarge 2009). Some examples include estriol, estradiol, estrone, progesterone and testosterone. There are many commercially available, FDA-approved bioidentical hormones in various forms and dosages. The following products are available: in pill form, Estrace or Innofem; vaginal cream for vaginal symptoms such as Estrace; patches

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such as Alora, Climara, Estraderm; topical gels Estrogel/Elestrin; and ring forms Estring and Fermin. Progesterone forms include in pill form Prometrium, and as vaginal gel Crinone 4%. Combined formulations include: Combipatch (Estradiol and norethindrone acetate), Prefest (pill) and Limara Pro (patch). By contrast, synthetic hormones differ structurally compared to human hormones. These compounds typically contain a chemically conjugated functional group to prevent the breakdown of the hormone before it reaches the circulation (Bosarge 2009). Examples include conjugated equine estrogen (CEE) or Premarin, and medroxyprogesterone acetate (MPA). The following diagrams show the molecular structure of biological estrogens and progesterone, compared to the synthetic forms that are used in conventional HRT and are sometimes referred to as â&#x20AC;&#x153;natural hormonesâ&#x20AC;?. The bioidentical hormones have a molecular structure identical to the biological hormones. Rationale for HRT The use of hormones in the treatment of peri- and postmenopausal symptoms has a long history dating from the 1960s. Hormone replacement therapy (HRT) is often prescribed to treat symptoms associated with menopause, including hot flashes, sleep disturbance and night sweats (Schmidt 2006). However, since the publication of the Womenâ&#x20AC;&#x2122;s Health Initiative Study (WHI) reporting an increased risk of various cardiovascular events and cancers, many women suffering from peri- and postmenopausal symptoms have turned to Figure 1. Structure of biological hormones (Left column) compared to synthetics used in conventional hormone replacement therapy (Right column)

the use of BHRT. BHRT is perceived as an effective and safer alternative to conventional treatment with synthetic hormones. Before menopause, ovarian follicles are the source of greater than 90% of estrogen, particularly estradiol. During pregnancy, estriol is the most active form of estrogen. After menopause, the conversion of androstendione to estrone by non-ovarian tissues is the main source of estrogen. Relief of hot flashes in postmenopausal women can usually be achieved by maintaining serum estradiol levels at 40-50 pg/ml, the lowest level of estradiol that is expected to be seen in a typical menstrual cycle (Schmidt 2006). Co-administration of a progestogen is still the standard method used in order to prevent estrogen-induced endometrial hyperplasia (Emons 2004), but co-administration of a synthetic progestin has its own side effects. Estrogen receptor subtypes The conflicting results regarding the safety of estrogen use may be in part due to the different forms of estrogen. Each form exhibits different binding affinity and selectivity to estrogen receptors, which is responsible for mediating a different physiologic effect. Estrogenic effects are mediated through two different estrogen receptor subtypes: estrogen receptor-alpha (ER-a) and estrogen receptorbeta (ER- B). ER-a promotes breast cell proliferation, while ER- B inhibits proliferation and prevents breast cancer development via G2 cells cycle arrest (Holtorf 2009). Estradiol equally activates ER-a and ER- B, while estrone selectively activates ER-a at a ratio of 5:1. In contrast, estriol selectively binds ER- B at a ratio of 3:1(Holtorf 2009). This suggests that estriol is strongly implicated in breast cancer prevention, while the other forms of estrogens may play a role in breast cancer promotion (Holtorf 2009). Due to minimal (<0.4%) conversion of intravenously administered estradiol or estrone to estriol, given its protective qualities, estriol is physiologically important in postmenopausal women. Therefore it is advisable to coadminister estriol with estradiol (Schmidt 2006). The synthetic counterpart of endogenous estrogens, CEE (Premarin), also selectively binds ER- B. Its components are potent downregulators of the ER- B receptor

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The The Journal Journal of of IHP IHP

subtype that has anticancer effects. In addition, the concomitant use of synthetic progestins along with CEE synergistically down-regulates ER- B receptors (Isaksson 2002), which is another possible mechanism underlying the breast cancer-promoting effect of CEE. CEE also contains at least one particularly potent carcinogenic estrogen, 4hydroxy-equilenin, which promotes cancer by inducing DNA damage (Holtrof 2009). In breast cancer survivors, estrogen therapy is especially controversial. However, breast cancer survivors have a high prevalence of severe menopause symptoms due to the induction of a premature menopause with chemotherapy and/or tamoxifen. It is important to find a therapy that is effective and safe for this patient population (Al-Baghdadi 2009). Progesterone versus progestins A review of the studies by Holtorf, Opatrny, and L’Hermite reveals that the use of synthetic progestins is associated with a higher risk of cancer compared to bioidentical progesterone (Holtorf 2009, L’Hermite 2008, Opatrny 2008). In particular, two large randomized controlled trials including the Women’s Health Initiative (WHI) and the Heart and Estrogen/progestin Replacement Study (HERS) have shown that use of CEE accompanied by progestins is associated with increased risk of breast cancer (Chlebowski 2003, Hulley 2002). In the WHI study, risk was increased 24% (HR 1.24, 95% CI 1.01–1.54) compared with placebo after 5.6 years (Chlebowski 2003), while in the HERS study, there was a non-significant 27% increase in risk (HR 1.27, 95% CI 0.84–1.94) compared to non-use after six years (Hulley 2002). Conversely, important data on the protective effects of bioidentical progesterone comes from the French E3N cohort (Fournier 2005, 2008). In this study, Fournier et al prospectively assessed the risk of breast cancer associated with HRT use in a cohort of over 80,000 postmenopausal women (2005, 2008). Compared to non-use, use of estrogen alone resulted in significantly increased risk of breast cancer, HR 1.29 (95% CI 1.02-1.65) (Fournier 2008). However, in combination regimens, this was modified according to the type of progestagen used. As in the RCTs cited above, breast cancer risk was significantly increased by the use of HRT containing synthetic progestins, however in this study there was

no increase with HRT containing micronized progesterone (estrogen-progesterone combination) (Fournier 2008, 2005). For example, when analyzing the risk of breast cancer associated with use of transdermal estrogen, estrogen alone was associated with non-significantly increased breast cancer risk, HR1.28 (0.98–1.69); on the other hand, use of transdermal estrogen in combination with the progestins chlormadinone acetate or medrogestone resulted in significant elevations in beast cancer risk, HR 1.48 (1.05–2.09) and 2.03 (1.39–2.97), respectively. Use of transdermal estrogen in combination with bioidentical progesterone however resulted in minimally changed risk compared to HRT non-use, 1.08 (0.89–1.31). An earlier analysis of this cohort, published in 2005, reported a similar relationship. These 2005 findings are depicted in Figure 2. In conclusion, this study suggests that after a mean 8.1 years follow-up, use of bioidentical progesterone conferred protective effects against breast cancer, compared to HRT utilizing synthetic progestins (Fournier 2008).

In a review by Campagnoli et al, further data is reported to the effect that synthetic androgenic (testosterone-derived) progestins might, when combined to estrogens, increase breast cancer risk through androgen-like effects, for instance by increasing IGF-1 activity (2005). IGF-1 exerts potent mitogenic and anti-apoptotic effects on breast cancer cells, in synergy with estrogens. By comparison, use of continuous bioidentical progesterone (100 mg/day), together with transdermal estradiol, failed to increase IGF-1 concentrations over a six month period (Campagnoli 2005). Table 1 summarizes additional evidence comparing the effects of bioidentical progesterone vs. synthetic progestins, as presented by Holtorf 2009 and Schmidt 2006. Routes of administration A few studies have investigated the impact of using transmucosal vaginal estrogen preparations on breast cancer recurrence and mortality. The results of these studies are encouraging, demonstrating that topical estrogen usage was not associated with an increased risk of cancer recurrence; however, the need for randomized, controlled trials was emphasized. The lack of convincing evidence that topical estrogen replacement therapy February / March 2014 l www.ihpmagazine.com 67

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(ERT) increases recurrence and breast cancerrelated mortality may encourage clinicians and patients to consider the less potent transmucosal vaginal estrogen preparations (Al-Baghdadi 2009). According to a review by Holtorf, transdermal estradiol, when given with or without oral progesterone, does not have detrimental effects on coagulation or risk for venous thromboembolism (VTE) (2009). In contrast, there is an increased risk for VTE with the use of CEE (both oral and topical with or without synthetic progestin) (Holtorf 2009). According to the ESTHER study, the relative risk of VTE with oral estradiol was significantly higher than transdermal estradiol. Also, estradiol combined with Norpregnane had a significant increased VTE risk compared with estradiol and Pregnane combination.

The lowest observed VTE risk was observed in estradiol with micronized progesterone (L’Hermite 2008). Minimizing side effects: oral versus topical applications When using HRT, a generally accepted principle is to prescribe the lowest effective dose on an individualized basis. Topical and transdermal formulations permit application without first-pass metabolism, and may reduce the stimulation of liver production of clotting proteins (Schmidt 2006). For instance, markers of blood clotting risk such as activated protein C resistance that are associated with oral estrogen use are not seen with transdermal administration (Oger 2003). Furthermore, while bioidentical hormones can be administered orally, they have poor oral

Table1. Differential effects of bioidentical progesterone vs. synthetic progestins, based on data reviewed by Holtorf 2009 and Schmidt 2006

• • • • •

•

• •

•

Progesterone Synthetic progestins (MPA) Outcomes related to risk of breast cancer Oral/ topical progesterone mitigates the • Postmenopausal women using CEE plus MPA risk of estrogen induced hyperplasia have more vaginal bleeding and breast tenderness than those using CEE plus oral Down regulates ER-α in the breast progesterone. Induces breast cancer cell apoptosis Diminishes breast cell mitotic activity • In normal human breast tissue, the ratio of Arrests human breast cancer cells in the progesterone receptors PRA:PRB is G1 phase by up-regulating cyclinapproximately 1:1. Synthetic progestins alter dependent kinase inhibitors and down the normal ratio of PRA:PRB, which is a risk regulating cyclin D1. factor for breast cancer. Inhibits estrogen-stimulated breast • 19-nortestosterone derived progestins bind to epithelial cells estrogen receptors in breast tissue and display significant intrinsic estrogenic properties in breast but not endometrial tissue. • May increase conversion of weaker endogenous estrogens into more potent estrogens, potentially contributing to their carcinogenic effects. • May promote formation of the genotoxic estrogen metabolite 16-hydroxyestrone. Outcomes related to cardiovascular disease • WHI study demonstrated that the addition of Progesterone maintains and augments MPA to Premarin resulted in increased risk of the cardioprotective effects of estrogen. heart attack and stroke. Progesterone either maintains or • MPA and other synthetic progestins generally augments estrogen’s positive lipid and negate the positive lipid effects of estrogen HDL effects. and show a consistent reduction in HDL. A number of studies have shown that • Addition of MPA to estrogen results in coronary artery spasms, which increases vasoconstriction, thus increasing the risk for the risk for heart attack and stroke is ischemic heart disease. reduced with the use of estrogen and/or • MPA has undesirable intrinsic glucocorticoid progesterone. activity. No changes in blood pressure are • Synthetic progestins increase insulin observed with progesterone in resistance when compared with estrogen and normotensive postmenopausal women, progesterone. but a slight reduction in blood pressure is shown in hypertensive women.

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The The Journal Journal of of IHP IHP bioavailability. Rapid metabolism by the liver and the hydrophobic nature of sex steroid hormones suggests that topical administration can be used as an alternative (Minkin 2004). According to Schmidt, transdermal administration of estradiol can maintain serum levels within a relatively narrow range for an extended period of time, with relatively low variation in bioavailability between individuals (2006). For progesterone, the large first-pass effect prevents most orally administered progesterone from reaching the blood plasma and generates metabolites with undesirable side effects; and vaginal bioavailability of progesterone is superior to oral (Schmidt 2006). A 1998 systematic review of 77 studies evaluating estrogen therapy found that while all routes were effective in the treatment of urogenital atrophy, the form with the least systemic absorption was estriol (administered orally or vaginally), followed by vaginal estradiol, as measured by pre- and post- therapy serum estradiol and estrone concentrations (Cardozo 1998). Side effects of local use are typically limited mild burning or pruritus, which generally disappear after several days of treatment (Raz 2001). Intravaginal estriol is well absorbed. Peak plasma levels of unconjugated estriol after insertion of 0.5mg of cream is comparable with those obtained after 8-12mg administered orally. Estriol replacement is an effective treatment in the treatment of urogenital complaints related to menopause, and may also have a role in the prevention of recurrent UTIs (Cardozo 1998, Raz 2001). Estrogen reduced vaginal pH and stimulates the proliferation of lactobacillus bacteria which compete with Enterobacteriaceae for vaginal colonization, which are the main pathogens of the urinary tract (Raz 2011). The absence of estrogen decreases the volume of vaginal muscles, resulting in slackness of the ligaments holding the uterus, the pelvic floor, and the bladder, resulting in the development of prolapse of the internal genitalia and predisposing to UTI (Raz 2001). The recommended dose is 0.5mg estriol twice weekly after a loading dose, applied for 14 days to vaginal area. Compounding BHRT Bioidentical hormones are commercially available in oral or topical preparations. Examples of commercially available estrogens include Estrace® and Climera®. Compounding pharmacists are able to prepare medications from scratch using individual ingredients that are mixed together to formulate a specific strength of medication (Fugh-Berman, 2007). Compounding bioidentical hormones can provide several advantages such as formulating a preparation to meet the specific needs of the patient. Additionally, BHRT’s can be compounded in various forms such as creams, lotions,

PLO gels, capsules, suppositories, troches or patches. Precise dosing allows for individualized treatment based on a patient’s symptoms and responses, avoiding unnecessary side effects (Bosarge 2009). For example, BHRTs can be compounded as a cream containing both estriol and estradiol at a minimum effective dose to minimize unwanted side effects. Convenient dosing and reduction of side effects may improve compliance when compared to conventional hormone replacement therapy (Bosarge 2009). Due to the variability of compounding practices between pharmacies, healthcare practitioners and patients should be cautious when choosing where they fill their medication. Compounding pharmacists can take training courses and receive certifications in compounding practice. It is advisable that physicians refer their patient’s to a reputable compounding pharmacy. Conclusion The concept of HRT was initiated in the mid-1960s with the goal of alleviating the symptoms of severe menopause and of cushioning against health risks associated with menopause. However, unease over its use surfaced following findings reported by the Women’s Health Initiative (WHI). Bioidentical hormones offer important benefits over conventional hormone replacement therapy. These include a reduced risk of breast cancer with use of progesterone compared with conventional progestin containing regimens, and lack of detrimental cardiovascular effects associated with progestins. Patients often are confused about the optimal approach to hormone replacement therapy. The choice of compounded bio-identical hormones may be appropriate when FDA-approved products do not provide the option of obtaining the desired medication such as transdermal testosterone; or the desired dose, for instance natural progesterone in a dose <100 mg); or when an allergy precludes an FDA-approved product, such as peanut allergy and Prometrium. Informed MDs, NDs, and pharmacists can help their patient make better decisions based on needs, concerns, preferences, and the best available scientific evidence.

Acknowledgements The authors wish to thank Joyce Wan B.Sc.Phm and Amin Jagani, BPharm, RPh, MBA for their help and contribution to this paper. References Al-Baghdadi O., Ewies A.A.A. Topical estrogen therapy in the management of postmenopausal vaginal atrophy: an up-to-date overview. Climacteric 2009;(12):91-105.4. Bosarge PM, Freeman S. Bioidentical hormones, compounding, and evidence-based medicine: what women’s health practitioners need to know. Journal for Nurse Practitioners 2009;5:421-7. February / March 2014 l www.ihpmagazine.com 69

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Campagnoli C, Clavel-chapelon F, Kaaks R, Peris C, Berrino F. Progestins and progesterone in hormone replacement therapy and the risk of breast cancer. J Steroid Biochem Mol Biol 2005;96:95-108. Cardozo L, Bachmann G, McClish D, Fonda D, Birgerson L. Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the Hormones and Urogenital Therapy Committee. Obstet Gynecol. 1998 Oct;92(4 Pt 2):722-7. Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, Rodabough RJ, Gilligan MA, Cyr MG, Thomson CA, Khandekar J, Petrovitch H, McTiernan A, WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Womenâ&#x20AC;&#x2122;s Health Initiative Randomized Trial. JAMA. 2003; 289(24):3243-53. Emons G, Huschmand-Nia A, Krauss T, Hinney B. Hormone replacement therapy and endometrial cancer. Onkologie 2004;27:207-210. Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies; results from the E3N cohort study. Breast Cancer Res Treat 2008;107:103-11.

outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA. 2002; 288(1):58-66. Isaksson E, Wang H, Sahlin L, et al. Expression of estrogen receptors (alpha, beta) and insulin-like growth factor-1 in breast tissue from surgically postmenopausal cynomolgus macaques after long-term treatment with HRT and tamoxifen. Breast. 2002;11(4):295-300. Leonetti HB, Landes J, Steinberg D, Anasti JN. Transdermal progesterone cream as an alternative progestin in hormone therapy. Altern Ther Health Med 2005;11:36-38. Lâ&#x20AC;&#x2122;Hermite Marc, Simonici Tommaso, Fuller Sarah, Genazzani Andrea Riccardo. Could transdermal estradiol + progesterone be a safer postmenopausal HRT? A Review. Maturitas 60(2008)185-201. Minkin MJ. Considerations in the choice of oral vs. transdermal hormone therapy: a review. J Reprod Med 2004;49:311-320. Mueck AO, Seeger H. Breast cancer: are estrogen metabolites carcinogenic? Climacteric 2007; 10 (Supple.2); 62-5.

Fournier A, Berrino F, RiboliE, Avenel V, ClavelChapon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res. Treat. 2008; 107(1):103-111.

Oger E, Alhenc-Gelas M, Lacut K, Blouch MT, Roudaut N, Kerlan V, Collet M, Abgrall JF, Aiach M, Scarabin PY, et al. Differential effects of oral and transdermal estrogen/progesterone regimens on sensitivity to activated protein C among postmenopausal women: a randomized trial. Arterioscler Thromb Vasc Biol 2003;23:1671-1676.

Fournier A, Berrino F, Riboli E, Avenel V, ClavelChapelon F. Breast cancer risk in relation to different types of hormone replacement therapy in the E3NEPIC cohort. Int J Cancer. 2005 Apr 10;114(3):448-54.

Opatrny L, Dell`Aniello S, Assouline S, Suissa S. Hormone replacement therapy use and variations in the risk of breast cancer. BJOG 2008; 115:169-175.

Fugh-Berman A, Bythrow J. Bioidentical hormones for menopausal hormone therapy: variation on a theme. Journal of General Internal Medicine. 2007; 22:1030-1034. Holtorf K. The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy? Postgrad Med. 2009 Jan;121(1):73-85.

Raz R., Postmenopausal women with recurrent UTI. International Journal of Antimicrobial Agents 17 (2001) 269-271. Raz R. Urinary tract infection in postmenopausal women. Korean J Urol. 2011 Dec;52(12):801-8. Schmidt JW, Wollner D, Curcio J, Riedlinger J, Kim L. S. Hormone replacement therapy in menopausal women: Past problems and future possibilities. Menopause. Gynecological Endocrinology.2006;22(10): 546-577.

Hulley S, Furberg C, Barrett-Connor E, Cauley J, Grady D, Haskell W, Knopp R, Lowery M, Satterfield S, Schrott H, Vittinghoff E, Hunninghake D, HERS Research Group. Noncardiovascular disease 61 www.ihpmagazine.com l October 70 February2013 / March 2014

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METAGENICS ESTROVERA™ 80026945 Estrovera by Metagenics features a special extract of Siberian rhubarb root (Rheum rhaponticum) designed to reduce hot flashes and other menopausal symptoms without potential serious adverse events associated with conventional hormone therapies (HT). Menopause is the clinical term used after menstruation has ceased for one year, after which women are considered postmenopausal [1]. In the Western world, the age range for natural menopause is 40 to 58 years, with 51 being the median age for menopause. The average age of menopause in Canada is also 51, and it is estimated that women over age 50 will comprise almost one quarter (22%) of the population by the year 2026 [2]. Of all the menopausal symptoms, hot flashes (also referred to as hot flushes) are the most common and potentially debilitating. Nearly 80% of women in Western countries suffer from hot flashes, with 30% reporting hot flashes severe and frequent enough to seriously affect quality of life [3]. HT is considered the most effective medical treatment option for relief of hot flashes and other menopausal symptoms [4]. However, HT is currently recommended only for moderate to severe vasomotor symptoms due to potential increased risk of breast cancer, cardiovascular events and other unwanted side effects [1]. The North American Menopause Society recommends using the lowest possible dose for the shortest duration possible [3]. The Society for Obstetricians and Gynaegologists of Canada also recommends using the lowest effective dose for HT [2]. Women with a history of cardiovascular events, venous thromboembolism, breast or uterine cancer, or liver disease, should not use estrogen to alleviate vasomotor symptoms [1]. Among the natural non-pharmalogical therapies, phytoestrogens are the most popular and the most studied category. Phytoestrogens are plant substances found in soy, red clover, flax, hops, and others, that possess weak estrogenic activity by binding to estrogen receptors (ER). However, systematic review of literature found that phytoestrogens such as isoflavones, lignans, and 8-prenylnaringenin have, at best, only modest effect in ameliorating menopausal symptoms [5-7]. Since 1993, a special phytoestrogen extract from the root of Siberian rhubarb (Rheum rhaponticum) known in scientific literature as ERr 731™ has been recommended by healthcare practitioners in Germany for menopausal hot flashes and related complaints [8]. Unlike Chinese rhubarb (e.g., R. palmatum, R. officinale) or other medicinal rhubarb species that contain strong laxatives anthraquinones, the main constituents of ERr 731 are hydroxystilbenes, including rhaponticin, desoxyrhaponticin, rhapontigenin, and desoxyrhapontigenin [8]. They are found to be agonists of estrogen receptor β (ERβ) and do not display ERα activity in endometrial tissue in laboratory studies [9]. ERβ activation is involved in the estradiol-mediated reduction of hot flashes [10]. In tissues that express both ERα and ERβ, ERβ acts as a negative regulator of ERα and offers protection against ERα-mediated effects in the breast and endometrium [11, 12]. Clinical trials have demonstrated that 1 tablet (4 mg) daily of ERr 731 offers effective relief for common menopausal symptoms, including hot flashes [8, 10, 1315]. For example, in a multicenter, randomized, placebo-controlled clinical trial in which 112 perimenopausal women with menopausal symptoms received either 1 tablet of ERr 731 (n=56) or placebo (n=56) for 12 weeks, ERr 731 treatment compared with placebo treatment resulted in [15]: • A significant reduction of the Menopause Rating Scale (MRS) total score and in each individual MRS item score • A significant reduction in the number of hot flashes, from an average of 12 per day at baseline to 2.8 ±2.8 (mean ± SE) per day at 12 weeks • A significant reduction in the hot flash weekly weighted score In a long-term clinical study with subjects taking ERr 731 for up to 24 months, women reported continued symptom reduction to help improve quality of life through reduced anxiety, negative mood, and sleep disturbances [10]. Data from these clinical trials also show that ERr 731 is well tolerated; no ERr 731-related adverse events are observed. [8, 10, 13-15] ERr 731, the active ingredient in Estrovera, is available to healthcare practitioners in North America, exclusively from Metagenics, Inc. 6.

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

4 mg

7. 8.

9. 10.

References 1.

2. 3. 4. 5.

Nelson HD. Menopause. Lancet. 2008;371(9614):760770. Society of Obstetricians and Gynaecologists of Canada. Canadian Consensus Conference on Menopause, 2006 Update. J Obstet Gynaecol Can. 2006;28:S1-S112. Umland EM. Treatment strategies for reducing the burden of menopause-associated vasomotor symptoms. J Manag Care Pharm. 2008;14(3 Suppl):14-19. North American Menopause Society. The 2012 hormone therapy position statement of: The North American Menopause Society. Menopause. 2012;19(3):257-271. Coon JT, et al. Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis. Phytomedicine. 2007;14(2-3):153159.

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11. 12. 13. 14. 15.

Lethaby AE, et al. Phytoestrogens for vasomotor menopausal symptoms. Cochrane Database Syst Rev. 2007;(4):CD001395. Clarkson TB, et al. The role of soy isoflavones in menopausal health: report of The North American Menopause Society/Wulf H. Utian Translational Science Symposium in Chicago, IL (October 2010). Menopause. 2011;18:732-753. Heger M, et al. Efficacy and safety of a special extract of Rheum rhaponticum (ERr 731) in perimenopausal women with climacteric complaints: a 12-week randomized, double-blind, placebo-controlled trial. Menopause. 2006;13(5):744-759. Wober J, et al. Activation of estrogen receptor-beta by a special extract of Rheum rhaponticum (ERr 731), its aglycones and structurally related compounds. J Steroid Biochem Mol Biol. 2007;107(3-5):191-201. Hasper I, et al. Long-term efficacy and safety of the special extract ERr 731 of Rheum rhaponticum in perimenopausal women with menopausal symptoms. Menopause. 2009;16(1):117-131. Frasor J, et al. Response-specific and ligand dose-dependent modulation of estrogen receptor (ER) alpha activity by ERbeta in the uterus. Endocrinology. 2003;144(7):3159-3166. Lindberg MK, et al. Estrogen receptor (ER)-beta reduces ERalpha-regulated gene transcription, supporting a "ying yang" relationship between ERalpha and ERbeta in mice. Mol Endocrinol. 2003;17(2):203-208. Kaszkin-Bettag M, et al. Efficacy of the special extract ERr 731 from rhapontic rhubarb for menopausal complaints: a 6-month open observational study. Altern Ther Health Med. 2008;14(6):32-38. Kaszkin-Bettag M, et al. The special extract ERr 731 of the roots of Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women. Menopause. 2007;14(2):270-283. Kaszkin-Bettag M, et al. Confirmation of the efficacy of ERr 731 in perimenopausal women with menopausal symptoms. Altern Ther Health Med. 2009;15(1):24-34.

14-02-07 1:51 PM

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 parental therapy and by the cnpbc; one ce hour.

Mistletoe Therapy Improving Outcomes In Complementary Cancer Care By Sarah Vanderheyden, RPN and Heidi Fritz, MA, ND Sarah Vanderheyden, RPN 8 Leland Road, London, ON N6K 1T1 Heidi Fritz, MA, ND Bolton Naturopathic Clinic, 64 King Street West, Bolton, ON, L7E 1C7 www.boltonnaturopathic.ca

ABSTRACT: Mistletoe therapy is an herbal medicine best known for its role in complementary cancer care. Pioneered by Rudolf Steiner, mistletoe, also known as Viscum album L or European mistletoe, has its roots in anthroposophic medicine; today there is a large body of evidence supporting use of mistletoe injection therapy as an adjunctive cancer treatment. Lectins and viscotoxins found in mistletoe appear to be responsible for its antitumor and immune stimulating effects. Mistletoe therapy has been investigated for its effects on survival, quality of life, and tolerability of chemotherapy/ side effects associated with chemotherapy. Meta analyses and systematic reviews have demonstrated a survival benefit associated with use of mistletoe injection therapy alongside chemotherapy or as a supportive therapy. There is also a large body of evidence indicating that mistletoe therapy improves quality of life, with improvements in global quality of life as well as symptoms such as fatigue, nausea and vomiting, pain, sleep disturbances, loss of appetite, and constipation found in a preliminary study. Finally, mistletoe therapy appears to reduce side effects of chemotherapy without decreasing its effectiveness. This article will summarize the history of mistletoe therapy and assess the current evidence surrounding its use in the area of oncology, including breast, lung, and pancreatic cancers to name a few.

February / March 2014 l www.ihpmagazine.com 73

Introduction Mistletoe therapy is a leading complementary or adjunctive cancer therapy, widely used by naturopathic doctors and medical doctors working in integrative oncology, with known immune stimulatory and antitumor effects. Today an advanced therapy most often administered as a subcutaneous injection, mistletoe has a long history of use and has undergone considerable development over that period of time. Historically, mistletoe (Viscum album L, European mistletoe) has its roots in German anthroposophic medicine, developed by Rudolf Steiner (1861-1925) (Bar-Sela 2011). This system of medicine sought to “acknowledge a spiritual-existential dimension in humanity” (Hamre 2009) and its interaction with physical health and disease (Hamre 2009, Horneber 2010). Initially, mistletoe therapy was used in the treatment of menstrual disorders, epilepsy, high blood pressure, artherosclerosis, diabetes, asthma, migraines, neuralgias, haemorrhages, endometriosis, eczema, foot ulcers, and labour pains (Bar-Sela 2011, Ostermann 2009). In 1920, Steiner introduced mistletoe extract as a treatment for cancer, recommending an extract produced through a complex preparation method that combined sap from mistletoe harvested in the summer and in the winter (Ostermann 2009). Based on this, mistletoe therapy has been used as a cancer therapy for almost a century. During this time, additional types of extracts have been developed, and are in use today. Presently, mistletoe therapy enjoys a prominent role in complementary cancer therapy, and is the subject of a wealth of research evaluating its impact on cancer treatment outcomes including survival, side effects of chemotherapy, and quality of life. This paper will examine the current use of mistletoe therapy in oncology and discuss the research relating to its effects on cancer related outcomes. Sources and extracts European mistletoe (Viscum album, L) is a partially woody, semi-parasitic plant that grows on deciduous and coniferous trees including pine, apple, oak and spruce (Kelter 2007, Melzer 2009). The medicinal parts are the stems, including the sap, and the leaves (Melzer 2009). Mistletoe extracts vary according to the type of plant material used, extraction method, as well as the type of tree that the mistletoe used grows on. The host tree that the product is derived from is denoted by a suffix at the end of the preparation name, for instance, Helixor-M is from mistletoe growing on the apple tree (Malus). Older, anthroposophic extracts are produced through a standardized manufacturing method but are not standardized to their constituents; while newer, “phytotherapeutic” extracts are standardized to their mistletoe lectin (ML-1) content 74 www.ihpmagazine.com l February / March 2014

(Melzer 2009). For instance, Eurixor is reported to contain between 50-70ng ML-1 per mL (NCI 2013). Helixor is standardized to its biological activity: degree of cytotoxic effects against a specific leukemia cell line. Iscador may contain between 0.0001–20 mg per mL, however this content refers to the amount of plant material rather than specific constituents such as lectins (Mistel-therapie 2014). The best-known extracts in North America are Helixor and Iscador. Helixor is a cold-water extract, while Iscador is a fermented extract of fresh leafy shoots and fruits harvested in the summer and winter (Ostermann 2009). Other commercially available extracts include Abnoba, Isorel, and Iscucin. Iscucin is produced in accordance with the German Homeopathic Pharmacopoeia. Phytotherapeutic extracts include Eurixor and Lektinol. Table 1 compares the characteristics of selected mistletoe extracts (adapted from Melzer 2009). Pharmacology European mistletoe contains many constituents, including lectins, viscotoxins, amino acids, flavonoids, phenylpropanoids, triterpenes, phytosterol, alkaloids, polyalcohols, and polysaccharides (Melzer 2009). The active components thought to be responsible for mistletoe’s antitumor effects are mistletoe lectins (ML), and less so, viscotoxins. Lectins are glycoproteins capable of binding to the outside of cells (NCI 2013). Three classes of lectins have been identified: ML-I, ML-II, and ML-III depending on what type of surface molecule they bind (Melzer 2009). Lectins possess direct cytotoxic effects, inhibiting protein synthesis and triggering apoptosis, as well as indirect antitumor effects through stimulation of cytokine release, and increasing NK cell and macrophages activity (Bar-Sela 2011, Kelter 2007). Viscotoxins are small polypeptides related to thionins and have cytotoxic effects (Bar-Sela 2011, Melzer 2009). Viscotoxins possess immunogenic effects, inducing production of anti-viscotoxin antibodies and causing rapid lysis of the cell membrane; and enhance cytotoxic T-cell activity, oxidative granulocyte bursting, and phagocytosis (Bar-Sela 2011, Klein 2002). Viscotoxins also inhibit cell division through inhibition of DNA and RNA synthesis (Bar-Sela 2011). Tumour Cell Growth Mistletoe therapy has been shown to inhibit tumour cell growth independently as a monotherapy as well as when used in conjunction with chemotherapy. This is effected both by direct cytotoxic effects mediated by the lectin- and viscotoxin- components as described above, as well as indirectly through immune stimulation (Bar-Sela 2011). Mistletoe therapy inhibits cell cycle progression, and induces tumour cell apoptosis and removal through phagocytosis (Friedel

The Journal of IHP – Continuing Education Table 1. Characteristics of Select Mistletoe Extracts (adapted from Melzer 2009) Preparation

Method

Host tree

Harvest

Admini stration

Dosage

Standardiz ation

apple (M:Malus)

summer and winter

0.01–50 mg/amp

process

Anthroposophic extracts Helixor

aqueous (herb)

fir (A: Abies)

(1 ml); or

pine (P: Pinus)

100 mg (2 ml) Iscador

aqueous lactoM,A,P, fermented (herb) elm (U: Ulmus)

summer and winter

0.0001–20 mg per amp (1 ml)

process

M, A, P

summer and winter

SC, IM

1–60 mg

process

oak (Q: Quercus) Isorel

aqueous (whole plant)

Phytotherapeutic extracts Eurixor

aqueous (herb)

poplar

winter

SC, IC, IV

1mg or 70ng per amp (1 ml)

ML-I

Lektinol

aqueous (herb)

poplar

winter

SC, IV

0.02–0.07 mg or 15 ng per amp

ML-I

(0.5 ml)

Legend: amp ampoule; IC intracoelomic (in the abdominal cavity); IM intramuscular; IV intravenous; ML mistletoe lectins; SC subcutaneous

2009). We describe two case reports of mistletoe therapy as monotherapy, followed by stronger evidence for its use as an adjunctive treatment alongside chemotherapy. Two case reports describe decreases in tumour size in response to intratumoral mistletoe injections among patients not undergoing chemotherapy (Orange 2010). A patient diagnosed with Merkel cell cancer was treated with subcutaneous and intravenous mistletoe therapy over a period of 9.8 months, during which the patient received no other anti-cancer treatment (Orange 2010). A second patient diagnosed with bilateral breast cancer, who declined cancer staging and surgical treatment, received subcutaneous and intratumoral mistletoe injections over a period of 31 months. Both patients experienced complete and durable remissions following use of mistletoe as a monotherapy (Orange 2010). A much higher grade of evidence, a 2008 Cochrane review, analyzed twenty-one studies of

mistletoe therapy in adult patients with cancer (Horneber 2008). Of these 21 studies, seven provided data on tumour response. Two of seven studies demonstrated additive benefit associated with combined mistletoe plus chemotherapy, compared to chemotherapy alone (Borrelli 2001, Lange 1993). The remaining five studies failed to demonstrate significant benefit on antitumor response compared to standard care alone, however there was no evidence of harm (Horneber 2008). Survival Data from several systematic reviews and meta-analysis indicate that mistletoe therapy has a survival benefit (Horneber 2008, Kienle 2009, Ostermann 2009, Ostermann 2012). These studies are summarized in Table 2. Ostermann et al performed two systematic reviews and meta analyses including over 50 studies and concluded that mistletoe therapy in addition to standard care resulted in approximately 40% improved survival, compared to standard care alone: HR 0.59 (95%CI 0.53- 0.66 and 0.50-0.70), where HR February / March 2014 l www.ihpmagazine.com 75

<1.0 favours mistletoe (2009, 2012). There was evidence of publication bias, undermining the strength of these findings, however these are nonetheless notable findings. A third, 2009 systematic review assessing the effectiveness of mistletoe in 19 RCTs, 16 nonrandomized studies, and 11 cohort studies of patients with breast or other gynaecological cancer found that 12 of 22 studies showed significant benefits on survival, and three of nine studies showed significant benefits for remission or time to relapse (Kienle 2009). Finally, the 2008 Cochrane review included twenty-one studies, of which thirteen evaluated survival as an endpoint (Horneber 2008). Six of these 13 studies showed a survival benefit associated with mistletoe therapy, although it was noted that they lacked methodological rigor. Collectively, the weight of data from these reviews suggests that despite certain limitations in the literature, mistletoe may have clinically important anticancer effects. A 2013 randomized controlled trial recently assessed mistletoe therapy in 72 patients with advanced nonsmall-cell lung cancer (NSCLC) (Bar-Sela 2013). All patients received chemotherapy with carboplatin plus gemcitabine or pemetrexed, and were then randomized to receive either mistletoe or no additional treatment. Iscador was dosed three times weekly until progression. This study found a non-significant improvement in time to tumour progression and overall survival associated with mistletoe therapy. Time to tumour progression was 6.0 months in the mistletoe group compared to 4.8 months in the control group. Overall survival (OS) was 15.9 months in the mistletoe group compared to 13.3 months in the control group. Importantly, fewer patients in the mistletoe group required chemotherapy dose reductions (13% versus 44%, p=0.005), experienced grade 3-4 non-haematological toxicities (16% versus 41%, p=0.043), or had hospitalizations (24% versus 54%, p=0.016). Another recently published randomized controlled trial assessed overall survival among 220 patients with advanced pancreatic cancer not receiving other cancer therapy (Troger 2013). Patients were randomized to treatment with mistletoe or no treatment, although both groups received the best available supportive care. Mistletoe was dosed subcutaneously three times per week, with the primary endpoint being overall survival (OS) at 12 months. At the time of this writing, interim results are available, showing median OS as 4.8 months for the mistletoe group, compared to 2.7 months for control patients (prognosis-adjusted hazard ratio, HR 0.49, p<0.0001). Among the subgroup of patients with a ‘good’ prognosis at baseline, median OS was 6.6 versus 3.2 months (HR 0.43, p<0.0001); while among

76 www.ihpmagazine.com l February / March 2014

the ‘poor’ prognosis subgroup, median OS was 3.4 versus 2.0 months, respectively (HR 0.55, p=0.0031). There were no side effects related to mistletoe. These interim results indicate a significant survival benefit associated with use of mistletoe, in this case even as a monotherapy in advanced cancer patients. Quality of Life Quality of life (QOL) has proved to be a very important component in terms of cancer treatment. At certain stages of disease, patients are no longer candidates for curative treatment. As a result, practitioners and members of the health care team focus on prolonging life without compromising quality of life, and on relieving symptoms (Bar-Sela 2012). Clinical data derived from studies of mistletoe therapy indicates an improvement in quality of life and decrease in side effects when used alongside chemotherapy (Bar-Sela 2013, Bussing 2012, Kim 2012). A 2012 RCT found that mistletoe significantly improved QOL (global health) (p <0.01), and increased leukocyte- and eosinophil counts (p ≤0.01) in 32 resected gastric cancer patients starting chemotherapy with doxifluridine, a 5-fluorouracil prodrug, compared to chemotherapy alone (Kim 2012). Diarrhea was also less frequently reported (7% vs. 50%, p=0.014) in the mistletoe group. A cohort study of 25 patients with various cancers reported similar findings, with improvements in QOL as measured by the EORTC QLQ-C30 questionnaire following three months of mistletoe therapy (Brandenberger 2012). In a 2012 meta analysis, Bussing found a moderate effect size for Iscador in improving quality of life when used alongside chemotherapy, standardized mean difference 0.56 (95%CI 0.41-0.71) (Bussing 2012). Similarly, a 2010 systematic review by Kienle found that of the 26 RCTs included, 22 reported a QOL benefit associated with use of mistletoe extracts, with the remaining four studies showing either no benefit or not reporting results (2010). Improvement was seen for coping, fatigue, sleep, exhaustion, energy, nausea, vomiting, appetite, depression, anxiety, ability to work, and emotional and functional well-being. The 2008 Cochrane review found that of 16 trials evaluating these outcomes, 14 showed significant benefits on QOL, performance score, or side effects of chemotherapy (Horneber 2008). Side Effects of Chemotherapy Mistletoe therapy may improve the tolerability of treatment and offset the need for dose reductions among patients undergoing chemotherapy. Most of the clinical research on mistletoe in oncology has been

The Journal of IHP – Continuing Education Table 1. Evidence on Mistletoe in Oncology from Systematic Reviews of the Literature

Ref

Design

Cancer type(s)

Intervention

Endpoint

Results

Büssing 2012

Meta analysis

Mistletoe (Iscador) in addition to standard care, compared to standard care alone

QOL

Overall treatment effect favoured Iscador. Standardized mean difference = 0.56 (95%CI 0.41-0.71), indicating a moderate effect. However, the methodological quality of the studies was poor.

Ostermann 2012

Retrolective meta analysis of data derived from N= 4 German cohort studies (N=3324 patients)

Breast

Mistletoe (Iscador) in addition to standard cancer therapy (chemo, surgery, etc), compared to standard therapy alone

Survival

HR survival: HR 0.59 (95%CI 0.50-0.70). (HR <1.0 favours mistletoe therapy.)

Mistletoe (Iscador) in addition to standard cancer therapy (chemo, surgery, etc), compared to standard therapy alone

Survival

Overall, HR survival 0.59 (95%CI 0.53- 0.66).

Mistletoe extracts in addition to standard care, compared to standard care alone.

QOL & reduction of SE of chemo

Meta Analysis

N=13 prospective & controlled studies (9 randomized)

Melanoma Colorectal Pancreatic

Ostermann 2009

Systematic review (n=49 studies) and meta analysis of N= 41 RCTs and non-randomized studies

Breast Ovarian Colorectal

Randomized studies showed less effect than non-randomized studies (ratio of HRs: 1.24, CI: 0.79 to 1.92, p = 0.35). There was suggestion of publication bias on funnel plot analysis.

Lung Skin GI cancers Renal Systematic Reviews Kienle 2010

Systematic review N=26 RCTs and 10 nonrandomized controlled trials

Breast & gynaecolog ical cancers GI cancer Lung Head & neck

Improvement was seen for the following: coping, fatigue, sleep, exhaustion, energy, nausea, vomiting, appetite, depression, anxiety, ability to work, and emotional and functional well-being in general.

6 different mistletoe extracts were investigated, in order of most studies to least: Iscador, Helixor, Eurixor, Isorel, Lektinol, Abnoba

Kienle Kienle 2009 2009

Systematic Systematic review review N=19 RCTs, RCTs, 16 16 nonnonN=19 randomized, controlled studies, 11 cohort studies.

Breast Breast & & gynaecolog gynaecolog ical cancers

Mistletoe Mistletoe (Viscum (Viscum album) album) extracts in in addition addition to to extracts standard care, care, compared compared standard to standard care alone.

Less consistent improvement was seen for pain, diarrhea, general performance, and side effects of conventional treatments.

Survival Survival Remission or or Remission time to relapse

SE of chemo QOL

Total of 2420, 6399 and 1130 patients, respectively.

Of the 26 RCTs, 22 reported a QoL benefit for VAE, 2 indicated no difference, 1 had mixed results, and 1 did not present the QoL results.

12 12 of of 22 22 studies studies showed showed significant significant benefits benefits on on survival. survival. 3 of 9 studies showed significant benefits for remission or time to relapse. 21 of 24 studies showed significant benefits for QOL and/ or tolerability of chemotherapy. Tumour regression was observed in cohort studies following high dose, local application. Study quality was better for more recent studies assessing quality of life, and lower for RCTs on survival and tumour behaviour that had small sample sizes.

Horneber 2008; Cochrane review

Systematic review N= 21 RCTs including 3484 patients

Adults with cancer of any type

Mistletoe extracts given as sole treatment, or given concomitantly with chemo- or radiotherapy compared with chemo or radiation alone. 5 different mistletoe extracts were investigated.

Survival Tumour response QOL SE of chemo Safety

Of the 13 trials investigating survival, 6 showed evidence of benefit, although they lacked high methodological quality. Of the 16 trials investigating the efficacy of mistletoe extracts for either improving QOL, performance score, or side effects of chemotherapy, 14 showed evidence of benefit. Mistletoe extracts were “usually well tolerated and had few side effects.” RCT reporting was deemed generally poor.

February / March 2014 l www.ihpmagazine.com 77

conducted among patients also undergoing standard care. For instance, the study by Bar-Sela cited above showed that there were significantly fewer dose reductions as well as non-hematological toxicities among NSCLC patients receiving mistletoe (2013). The study by Kim showed a reduction in the incidence of diarrhea among patients on doxifluridine (2012). In addition, several systematic reviews indicate a reduction in side effects of chemotherapy, although in most reviews, this was an endpoint combined with quality of life (Kienle 2010, 2009). Mistletoe therapy has also been shown to improve symptoms during cancer patients’ aftercare, defined as the five years following the completion of standard care (Beuth 2008). Data from a cohort of 681 breast cancer patients found that use of mistletoe was associated with decreased overall symptoms (56% versus 70%) as well as a reduction in specific symptoms including mucositis, fatigue, pain, and headache during aftercare, compared to patients not using mistletoe (Beuth 2008). Safety Mistletoe therapy has a good safety profile, with most side effects being mild to moderate soreness and inflammation at injection sites, headache, fever, and chills (NCI 2013). Although rare, allergic reactions and anaphylaxis are possible. Dose escalation strategies are used to prevent such reactions. Interactions Based on a large volume of data evaluating the use of mistletoe alongside standard care including chemotherapy, and the existence of several meta analyses showing survival benefits (Table 1), mistletoe appears to have a good safety profile alongside chemotherapy. If anything, there appear to be beneficial interactions such that mistletoe reduced side effects of chemo, while improving cancer treatment outcomes such as survival and time to tumour progression (Bar-Sela 2013, Ostermann 2012). In particular, human studies have evaluated mistletoe therapy alongside the following chemotherapy regimens, finding that there was no evidence of mistletoe reducing the anticancer effectiveness of chemotherapy: gemcitabine (Mansky 2013), carboplatin plus gemcitabine or pemetrexed (Bar-Sela 2013), CMF (cyclophosphamide, methotrexate and fluorouracil) (Auerbach 2005, Horneber 2008), 5-fluorouracil (Heiny 1997, Horneber 2008), and cisplatin and ifosfamide (Lange 1993, Horneber 2008) (Lange 1993 is an unpublished study cited by Horneber 2008). Newly published in vitro experiments suggest that mistletoe is unlikely to reduce the effectiveness of the following chemotherapy drugs: doxorubicin, gemcitabine, docetaxel and mitoxantrone, 78 www.ihpmagazine.com l February / March 2014

and docetaxel and cisplatin (Weissenstein 2014). The study reported that “VAE [Viscum album extract] did not inhibit chemotherapy induced cytostasis and cytotoxicity in any of our experimental settings. At higher concentrations VAE showed an additive inhibitory effect [with chemotherapy drugs]” (Weissenstein 2014). Conclusion Mistletoe therapy has a long history of use as a complementary cancer therapy, dating from the 1920s. This therapy demonstrates a good safety profile as well as important benefit on several endpoints related to cancer, including up to 40% improvement in survival, as well as benefits tof quality of life and tolerability of chemotherapy. There are several different mistletoe extracts commercially available, however the best-known and the most researched extracts are Iscador and Helixor. Mistletoe constituents, namely lectins and viscotoxins, exert direct and indirect cytotoxic effects and acts as an immune stimulant. There is a wealth of clinical data on European mistletoe, including several systematic reviews and meta-analyses; however, there is still a need for more rigorous study design and trial reporting in future research on this agent. References Auerbach L, Dostal V, Vaclavik-Fleck I, Kubista E, Rosenberger A, Rieger S, et al.[Signifikant höherer Anteil aktivierter NK–Zellen durch additive misteltherapie bei chemotherapierten Mamma–Ca–Patientinnen in einer prospektiv randomisierten doppelblinden Studie]. Fortschritte in der Misteltherapie - Aktueller Stand der Forschung und klinische Anwendung. Essen: KVC Verlag, 2005:1–11. [Cited by Horneber 2008] Bar-Sela G. White-Berry mistletoe (Viscum album L.) as complementary treatment in cancer: does it help? European Journal of Integrative Medicine. 2011;3(2):55-62. Bar-Sela G, Wollner M, Hammer L, Agbarya A, Dudnik E, Haim N. Mistletoe as complementary treatment in patients with advanced non-small-cell lung cancer treated with carboplatin-based combinations: a randomised phase II study. Eur J Cancer. 2013 Mar;49(5):1058-64.

The Journal of IHP – Continuing Education Borrelli E. Evaluation of the quality of life in breast cancer patients undergoing lectin standardized mistletoe therapy. Minerva Medica 2001;92(Suppl 1 Nr 3):105–7. Brandenberger M, Simões-Wüst AP, Rostock M, Rist L, Saller R. An exploratory study on the quality of life and individual coping of cancer patients during mistletoe therapy. Integr Cancer Ther. 2012 Jun;11(2):90-100. Büssing A, Raak C, Ostermann T. Quality of life and related dimensions in cancer patients treated with mistletoe extract (iscador): a meta-analysis. Evid Based Complement Alternat Med. 2012;2012:219402. Friedel WE, Matthes H, Bock PR, Zänker KS. Systematic evaluation of the clinical effects of supportive mistletoe treatment within chemo- and/or radiotherapy protocols and long-term mistletoe application in nonmetastatic colorectal carcinoma: multicenter, controlled, observational cohort study. J Soc Integr Oncol. 2009 Fall;7(4):137-45. Hamre HJ, Kiene H, Kienle GS. Clinical research in anthroposophic medicine. Altern Ther Health Med. 2009 Nov-Dec;15(6):52-5. Heiny BM, Albrecht V. [Komplementäre Therapie mit Mistellektin–1–normiertem Extrakt – Lebensqualitätsstabilisierung beim fortgeschrittenen kolorektalen Karzinom – Fakt oder Fiktion?]. Medizinische Welt 1997;48:419–423. [Cited by Horneber 2008]. Horneber MA, Bueschel G, Huber R, Linde K, Rostock M. Mistletoe therapy in oncology. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD003297. Kelter G, Schierholz JM, Fischer IU, Fiebig HH. Cytotoxic activity and absence of tumor growth stimulation of standardized mistletoe extracts in human tumor models in vitro. Anticancer Res. 2007 Jan-Feb;27(1A):223-33. Kienle GS, Glockmann A, Schink M, Kiene H. Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research. J Exp Clin Cancer Res. 2009 Jun 11;28:79. Kienle GS, Kiene H. Review article: Influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies. Integr Cancer Ther. 2010 Jun;9(2):142-57. Kim KC, Yook JH, Eisenbraun J, Kim BS, Huber R. Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma - a randomized, controlled pilot study. BMC Complement Altern Med. 2012 Oct 3;12:172.

Klein R, Classen K, Berg PA, Lüdtke R, Werner M, Huber R. In vivo-induction of antibodies to mistletoe lectin-1 and viscotoxin by exposure to aqueous mistletoe extracts: a randomised doubleblinded placebo controlled phase I study in healthy individuals. Eur J Med Res. 2002 Apr 30;7(4):155-63. Lange O, Scholz G, Gutsch J. Modulation of the subjective and objective toxicity of an aggressive chemoradiotherapy with Helixor [Modulation der subjektiven und objektiven Toxizität einer aggressiven Chemo/Radiotherapie mit Helixor]. 1993: 17268. [Cited by Horneber 2008]. Mansky PJ, Wallerstedt DB, Sannes TS, Stagl J, Johnson LL, Blackman MR, Grem JL, Swain SM, Monahan BP. NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors. Evid Based Complement Alternat Med. 2013;2013:964592. Melzer J, Iten F, Hostanska K, Saller R. Efficacy and safety of mistletoe preparations (Viscum album) for patients with cancer diseases. A systematic review. Forsch Komplementmed. 2009 Aug;16(4):217-26. Mistel-therapie. Iscador. No date updated provided. http://www. mistel-therapie.de/index.php5?page=39&lang=1 Accessed 2 February 2014. NCI, National Cancer Institute. Mistletoe Extracts PDQ. Updated 06/07/2013. URL: http://www.cancer.gov/cancertopics/pdq/cam/mistletoe/HealthProfessional/page1 Accessed 10 Jan 2014. Orange, M., Fonseca, M., Lace, A., Von Laue, H. B., Geider, S. (2010). Durable tumour responses following primary high dose induction with mistletoe extracts: two case studies. European Journal of Integrative Medicine. 2010;2(2):63-69. Ostermann T, Büssing A. Retrolective studies on the survival of cancer patients treated with mistletoe extracts: a meta-analysis. Explore (NY). 2012 Sep-Oct;8(5):277-81. Ostermann T, Raak C, Bussing A. Survival of cancer patients treated with mistletoe extract (iscador): a systemic literature review. Biomed Central. 2009;9:451-460. Tröger W, Galun D, Reif M, Schumann A, Stankovicec N, Milicevic M. Viscum album [L.] extract therapy in patients with locally advanced or metastatic pancreatic cancer: a randomised clinical trial on overall survival. Eur J Cancer. 2013Dec;49(18):3788-97. Weissenstein U, Kunz M, Urech K, Baumgartner S. Interaction of standardized mistletoe (Viscum album) extracts with chemotherapeutic drugs regarding cytostatic and cytotoxic effects in vitro. BMC Complement Altern Med. 2014 Jan 8;14(1):6.

February / March 2014 l www.ihpmagazine.com 79

Questions 1. The use of mistletoe therapy in the area of cancer was first developed by: a) Sir Frederik Banting b) Linus Pauling c) Rudolf Steiner d) Nicolaus Copernicus 2. Mistletoe is a semi-parasitic plant, growing upon other trees, including apple, fir, pine, oak, and others. The letter A at the end of Helixor-A designates an extract derived from mistletoe growing on which type of tree? a) Apple b) Fir c) Poplar d) Quercus 3. Phytotherapeutic mistletoe extracts are produced through a standardized manufacturing method but are not standardized to their constituents. a) True b) False 4. Which of the following is true about specific mistletoe extracts? a) Eurixor contains between 25-50ng ML-1 per mL b) Helixor is standardized to its biological activity against a breast cancer cell line c) Iscador is a fermented extract of leafy shoots and fruits harvested in the summer and winter d) All of the above 5. One of the two main active constituents in mistletoe thought to be responsible for its anticancer effects is which of the following: a) saponins b) alkaloids c) lectins d) beta-glucans 6. In a 2008 Cochrane review, 2 of 7 studies demonstrated an additive survival benefit associated with use of mistletoe in combination with chemotherapy, compared to chemotherapy alone. a)True b) False

7. A 2013 randomized controlled trial by Bar-Sela et al. reported that use of Iscador in patients with advanced non-small cell lung cancer (NSCLC) resulted in which of the following? a) a non-significant trend in time to tumour progression favouring the mistletoe group; b) evident lack of deleterious interactions between Iscador and the chemotherapy regimen: carboplatin plus gemcitabine or pemetrexed; c) fewer patients in the mistletoe group requing chemotherapy dose reductions, 13% versus 44%; d) All of the above 8. A 2012 systematic review by Bussing et al. reported that mistletoe was associated with a large effect size with respect to improving quality of life (QOL). a) True b) False 9. Subcutaneous mistletoe injections carry the potential risk for allergic reaction and anaphylaxis. As a result, gradual dose escalating strategies are used to minimize this risk. a) True b) False 10. Which of the following is true about the potential interactions between mistletoe and chemotherapy? a) Given that an additive survival benefit is shown by some studies, null effects by other, but no studies show harm on survival parameters associated with mistletoe therapy alongside chemotherapy, it appears that mistletoe does not reduce the effectiveness of chemotherapy; b) Mistletoe has been studied alongside the following regimens: gemcitabine; carboplatin with gemcitabine or pemetrexed; 5-fluorouracil; and cisplatin. c) In vitro studies report that combination of mistletoe with various chemotherapy drugs â&#x20AC;&#x153;did not inhibit chemotherapy induced cytostasis and cytotoxicityâ&#x20AC;? d) All of the above

FAX OR EMAIL ANSWERS TO: 416.703.6392 or philip@ihpmagazine.com Name: Address: City: Province: Postal Code: Phone: Email: Fax: Practice Registration #:

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PRODUCT MONOGRAPH

fast joint care+

Introduction greens+ whole body NUTRITION fast joint care+ by Genuine Health is a novel, rapidly acting formulation designed to help alleviate joint pain and stiffness. fast joint care+ is a patented ingredient containing naturally occurring combination of molecules derived from natural eggshell membrane (NEM), whole Gallusbody gallus. These molecules includefrom fibrous proteins suchisasa superfood collagen type I, glycosaminoglycans (GAGs)nutritional such as chondroitin greens+ NUTRITION, a new offering Genuine Health, concentrate designed as an all-in-one formula for sulfate andsupport. dermatan sulfate, sulftated glycoproteins such as glucosamine, hyaluronic acid, and a host to ofsupport other related proteins (Ruff health total body This convenient, great-tasting, and allergen-free product helps rebalance body systems immune and digestive through 2009a). inclusion of a 70% fermented ingredient blend, alkalinize the body, provide a wide spectrum of plant-based antioxidants and anti-inflammatory ingredients, and support mood cognitive function.Unlike the most commonly used medications for the condition, such as NSAIDs, NEM is fast joint care+ is unique as and a joint care product. a disease-modifying agent, meaning that it not only improves the symptoms of arthritis but also helps repair damaged tissue. NSAIDs carry The key feature ofsuch this formula is the fermented blend, which contains sources of essentialthis fatty acids (flaxseed, purslane, black cumin, and significant risks, as development of peptic ulcer disease, renalfermented failure, and hemorrhage; underscores the importance of developing sea fermented whole foods (carrot, tomato, kale, cocoa, and rice bran); fermented plant based protein fromthat brown fermented safebuckthorn); treatment alternatives (Vangsness 2009). Unlike theolive, natural alternatives glucosamine and chondroitin sulfate can rice; takeand several fibre. thewithin nutrients from these sources morenow bioavailable; as phytic acid thattreatment inhibit nutrient absorption weeksFermentation to act, NEMmakes works 7-10 days. New research indicatesremoves that fastanti-nutrients joint care+such is also an effective for non arthritic (Chen 2013); and introduces healthy bacteria to the gut, aiding digestion and immune function. Fermentation also improves the tolerability of foods joint pain and fibromyalgia. that otherwise trigger immune reactions, such as gluten (Calasso 2012).

Osteoarthritis The formula base is Vegan greens+ OTM, a combination of colorful plant-based antioxidants and alkalinizing nutrients that provides the equivalent of Osteoarthritis (OA)and is the most common musculoskeletal condition in Westernized approximately 27 million Americans TM six servings of fruits vegetables. A University of Toronto study has shown that greens+countries; significantly increases urine alkalinity after onlyare 14 days estimated to to placebo be clinically diagnosed with OA, while 46 millionhave are thought to bebeen affected bytoarthritis as a non-specific category compared (Berardi 2008). Plant-based foods upwards and their of antioxidants reproducibly shown be inversely associated with a host (Vangsness 2009, Lawrence 2008, Theis 2007). The impact of OA includes pain, loss of function and2012, mobility, physical and psychosocial of chronic diseases including cancer, cardiovascular disease, osteoporosis, and cognitive impairment (Bao Estruch 2013, Leenders 2013, Loef disability, of NSAID therapy, and financial costs to the healthcare system. Direct average annual per person medical 2012, Rivascomplications 2013). expenditures due to arthritis ranged from $1454- 2206 (Theis 2007).

Additional antioxidants in greens+ whole body NUTRITION include lutein from marigold, flavonoids from AuroraBlue® (a proprietary blend of wild Two initial pilot studies involving 11extract, and 26NeuroFactor subjects respectively with pre-existing joint disorders found in joint TM blueberries), a proprietary coffee bean that stimulates Brain-Derived Neurotrophic Factor significant (BDNF) andreductions protects against neuropain, joint stiffness, anda proprietary pain on range of motion (ROM) compared (Ruff After 7 days there wasDismutase a 25% reduction in that degeneration, as well as cantaloupe extract, Extramel®, thattoisbaseline particularly rich2009a). in the antioxidant Superoxide (SOD) and pain, while at 30 days there was a 51% reduction. At 30 days, there was a 43% improvement in flexibility. Nearly 50% of the patients supports brain health.

reported being pain free after 1 month.

Adult dosage: Mixdouble 1-2 scoops (16.2-32.4g) of greens+ body NUTRITION in 1-1 ½ cup (250-375mL) purewas water or juice. Shake If you A more rigorous, blinded RCT involving 67 whole subjects with osteoarthritis found similar effects. of NEM given at 500 mg well. per day are a new user of greens+, begin with 1 scoop daily and gradually increase to 2 scoops daily over a 3 week period. Take 2 hours before or after taking for 2 months. Researchers found significant improvements in pain and stiffness as graded by WOMAC (a clinically relevant OA assessment other medications.

tool) both at 10 days and at 60 days. After 10 days, 54% of subjects in the treatment group had a 20-30% reduction in pain, compared to 24% in the placebo group; at 60 days, 32% vs to 12% ≥50% reductionbreastfeeding, in pain. Similar demonstrated for deficiency, stiffness, with Caution: Consult a health care practitioner prior use had if you are pregnant, havefindings any typewere of acute infection, iron hypoten25% liver reduction at 10 days, and 53% at of 60liver days.trouble (Ruff(abdominal 2009b) pain, dark urine, jaundice) or are taking medications for diabetes, blood pressure, sion, disorder or develop symptoms

or seizures. Do not use if you are taking health products that affect blood coagulation (eg. blood thinners, clotting factor replacements, acetylsalicylic Non Arthritic Pain acid, ibuprofen, Joint fish oils, vitamin E). Hypersensitivity, such as an allergy, has been known to occur; in which case discontinue use.

In addition to studies on NEM, fast joint care+ as a whole has been specifically assessed in subjects with non arthritic joint pain. In a randomized study, 60 unmedicated subjects with chronic (but non-arthritic) joint pain were given either 500mg of fast joint Non medicinal ingredients: Stevia rebaudiana: organic steviacare+ leaf or placebo1.for one month.per Those in the fast joint care+ group reported reduction in post-exercise pain ratings, phosphate, with four times less pain than Table Ingredients 34.2g (2 scoops) & astevia leaf extract, natural flavor, tricalcium ascorbyl Vegan greens+group OTM base formulaunpublished data). This the placebo (Berardi, exciting finding shows that fast joint silicon care+ dioxide. is an effective therapy for those “weekend ~7.5g palmitate, maltodextrin, warriors” suffering from joint pain, and not exclusively for those suffering from osteoarthritis. Oryza sativa: fermented, sprounted whole grain brown rice protein concentrate Fibromyalgia (non-GMO; 80% protein)

12.5g

References:

Bao PP, et al. Fruit, vegetable, and animal food intake and breast cancer risk

hormone Alison receptor Bested, status. Nutr Cancer. 2012 Aug;64(6):806-19. An open-label pilot study supervised by Toronto area fibromyalgiaby specialist MD investigated the effects of 500mg of fast jointblend: care+ among 15 patients when given daily for eight weeks. Outcomes were measured using the Fibromyalgia Impact Fermented 2308mg Berardi JM, Logan AC, Rao AV. Plant based dietary supplement increases Linum usitatissimum (Organic flaxseed); Questionnaire (FIQ) and Brief Pain Inventory (BPI) scales before and at the of Nutr. the study. Results 1154mg urinary pH. conclusion J Int Soc Sports 2008 Nov 6;5:20.showed that Oryza sativacare+ (Rice bran); fast joint significantly improved sleep, pain while working (i.e. performing activities), and overall pain ratings in FM. 692mg Portulaca oleracea (Purslane plant); 231mg M, et al.towards The sourdough fermentation may enhance the recovery “Enjoyment of Life”, “Everyday Work” and “Missed Work” scalesCalasso also trended improvement (Bested, unpublished data) Daucus corota (Purple carrot root);

231mg from intestinal inflammation of coeliac patients at the early stage of the Olea europaea (Olive fruit); 231mg gluten-free diet. Eur J Nutr. 2012 Jun;51(4):507-12. Recommended Use(Tomato fruit); Solanum lycopersicum 231mg Brassica (Organic kaleContraindicated plant); 500 mgoleracea or one viridis capsule per day. in persons with allergy toetegg or egg products. Noofknown adverse 231mg Chen L, al. High-efficiency removal phytic acid in soyeffects. meal using twoHippophae rhamnoides (Sea buckthorn fruit); 231mg stage temperature-induced Aspergillus oryzae solid-state fermentation. J Sci Nigella sativa (Black cumin seed); References 231mg Phyllanthus emblica amlaReduces fruit); Joint Pain. Unpublished Berardi J. Egg Shell(Organic Membrane data. Food Agric. 2013 Apr 30. doi: 10.1002/jsfa.6209. 231mg Theobroma cacao (Organic cocoa seed) 6g Estruch et al; in PREDIMED Study Investigators. Primary prevention of Bested A. Summary of aVitaFibreTM pilot, open-label, study of eggshell membrane (fast joint R, care+) fibromyalgia patients. Completed April 2012. Unpublished Isomaltooligosaccharides: cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013 Apr data. (fermented; non-GMO) 4;368(14):1279-90. Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers 800 IU/ Vegan Vitamin (ergocalciferol from HM, Wolfe F; DNational Arthritis Data Workgroup. Estimates of arthritis other conditions in United States. Part II. 20mcg of the prevalence Leenders M, et al.and Fruit and rheumatic vegetable consumption andthe mortality: European Agaricus non-GMO, organic) Arthritis bisporus; Rheum. 2008 Jan;58(1):26-35. prospective investigation into cancer and nutrition. Am J Epidemiol. 2013 120mg Aug 15;178(4):590-602. Ruff KJ,erecta Winkler A, Jackson DeVore DP, Ritz BW. Eggshell membrane in the treatment of pain and stiffness from osteoarthritis of the knee: Tagetes (Marigold flowerRW, extract, 5% lutein)

a randomized, multicenter, double-blind, placebo-controlled clinical study. Clin Rheumatol. 2009 Aug;28(8):907-14.

100mg Loef M, et al. Fruit, vegetables and prevention of cognitive decline or Coffea arabica (NeuroFactoTM whole coffee fruit dementia: a systematic review of J Nutr Health Aging. 2012 Results Ruff KJ, DeVore DP, Leu MD, Robinson MA. Eggshell membrane: a possible new natural therapeutic forcohort joint studies. and connective tissue disorders. concentrate) Jul;16(7):626-30. from two open-label human clinical studies. Clin Interv Aging. 2009;4:235-40. 100mg Vaccinium & uliginosum Theis KA,ovalifolium Helmick CG, Hootman JM.Arthritis burden and impact are greater U.S. women than men: opportunities.J Womens Health Rivasamong A, et al. Mediterranean diet and intervention bone mineral density in two age TM (AuroraBlue wild Alaskan blueberry fruit) (Larchmt). 2007 May;16(4):441-53. 10mg groups of women. Int J Food Sci Nutr. 2013 Mar;64(2):155-61. Cucumis melo (Extramel® cantaloupe fruit juice Vangsness CT Jr, Spiker W, Erickson J. A review of evidence-based medicine for glucosamine and chondroitin sulfate use in knee osteoarthritis. concentrate)

Arthroscopy. 2009 Jan;25(1):86-94.

Hibiscus SAP PRODUCT MONOGRAPH

Hibiscus sabdariffa has been studied for its effects on blood pressure, lipid levels, blood-sugar regulation, and metabolic syndrome, as well as its antioxidant properties. Hibiscus contains anthocyanins (derived from anthocyanidins), polyphenols, glycosides, sterols, organic acids, polysaccharides, and some minerals.[3, 4] Hibiscus possesses pharmacological properties as well as a great safety profile that demonstrates that it promises as a treatment in cardiac and diabetic patients.[2]

Participants were divided into two groups and received either HSE capsules (500 mg bid) or placebo for 90 days. Participants who were overweight were also advised to achieve a 5% weight loss. Both groups realized similar but significant reductions in body weight and serum LDL-cholesterol levels from baseline. LDL cholesterol levels were similarly decreased by 18% in the HSE group and 12% in the placebo group. Serum triglycerides levels were decreased by 10% in the HSE group, but were not significantly impacted by the placebo.

HYPERTENSION

METABOLIC SYNDROME AND GLUCOSE REGULATION

Hibiscus sabdariffa beverages have been widely used in Mexico as a diuretic for treating concerns such as hypertension, hypercholesterolemia, liver disease, and gastrointestinal disorders.[3] In a clinical trial, researchers isolated the bioactive and characterized the mechanism through which hibiscus exerts its blood pressure lowering effects.[3] The active constituents anthocyanins delphinidin-3-O-sambubioside and cyanidin3-O-sambubioside were isolated by bioassay-guided purification.[3] These compounds were then shown to compete with angiotensin converting enzyme (ACE) for attachment at the active site,[3] suggesting that hibiscus demonstrates its antihypertensive effects via ACE inhibition.[3] In a randomized, double-blind, placebo-controlled trial, researchers compared Hibiscus sabdariffa dried extract containing 250 mg/d of total anthocyanins to 10 mg/d lisinopril in patients with stage I or II hypertension over a 4-week period.[2, 5] The group treated with hibiscus showed a reduction in systolic and diastolic blood pressure by 11.6% and 12.2%, respectively. The group treated with lisinopril manifested decreases in systolic and diastolic blood pressure by 15.8% and 15.7%, respectively. Lisinopril was significantly more effective at blood-pressure lowering than was hibiscus. Researchers demonstrated that patients treated with hibiscus showed decreased plasma ACE activity and reduced serum sodium levels without changing serum potassium levels.[2] The researchers concluded that hibiscus appears to exert its antihypertensive action through ACE inhibition and dieresis.[2, 5] In another study comparing hibiscus to captopril for hypertension, participants received either 10 g of HSE (10 g of dry calyx prepared in 500 mL water and steeped for 10 minutes providing 9.6 mg/d anthocyanins) or 25 mg captopril bid for 4 weeks.[2, 6] Both groups responded with significant reductions in blood pressure, whereas in the hibiscus group’s systolic blood pressure decreased by 10.2% and diastolic decreased by 12.3%. The captopril group had a reduction of 11.4% systolic and 14.3% diastolic, which was not significantly different compared to the hibiscus results.[2, 6]

CHOLESTEROL

Hibiscus sabdariffa extract (HSE) has been shown to lower plasma lipid levels and reduce damage to the liver.[7] Researchers have explored the hypolipidemic effects of a Hibiscus sabdariffa polyphenol extract (HPE) in a hamster model.[7] In this surrogate model of human heart disease, 3 groups were fed high-fat diets for 10 weeks: group 1 received no treatment, group 2 received HSE, while group 3 received HPE. Both treatments resulted in reductions in serum triglycerides and total cholesterol levels in a dose-dependent manner.[2, 7] However, the HPE group exhibited a more potent decrease in LDL cholesterol than the crude extract HSE group (2% polyphenols). In addition, the HPE group demonstrated an increase in HDL cholesterol levels in a dose-dependent manner.[7] Mechanistically, HPE decreased the amount of lipid in the hepatocyte by activating AMPK and via the reduction of SREBP-1, which inhibited the expression of fatty acid synthase and HMG-CoA reductase.[7] These researchers also found that HPE enhanced the expression of the LDL receptor, resulting in increased LDL cholesterol uptake and clearance by the liver.[7] In a clinical trial, a placebo-controlled, double-blind study was carried out in patients with LDL-cholesterol between 130 and 190 mg/dl.[8]

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Metabolic syndrome is strongly associated with insulin resistance, hypertension, obesity, and dyslipidemia.[9] Clinically, hibiscus has demonstrated the ability to reduce hypertension and hyperlipidemia, therefore researchers have been interested in investigating preventative effects of hibiscus in individuals with and without metabolic syndrome.[9] Participants were divided into two groups based on having metabolic syndrome or not, and then allocated into one of three treatment groups.[9] Group 1 was given a preventative diet, group 2 was supplemented with HSE capsules (100 mg/d), and group 3 was given both the preventative diet and HSE supplementation for 31 days. In participants with metabolic syndrome, HSE significantly reduced fasting glucose by 8.4%, total cholesterol by 10%, LDL cholesterol by 20%, and increased HDL cholesterol levels by 39%.[2, 9] In participants without metabolic syndrome, HSE also achieved significant reductions in fasting glucose by 6.7% and triglycerides by 23%, and increased HDL cholesterol levels by 10%. Researchers concluded that in addition to the well-documented hypotensive effects, hibiscus can also be used for individuals with metabolic syndrome–associated dyslipidemia.[9]

ANTIOXIDANT EFFECTS

The early stages of atherosclerotic lesions are caused by the oxidation of LDL-cholesterol.[2] CD36 is a scavenger receptor that binds and internalizes oxidized LDL molecules, mediating their uptake by macrophages and the formation of macrophage-derived foam cells.[2] In a recent study investigating the antioxidant activity of anthocyanin-rich hibiscus extracts, researchers found that hibiscus significantly decreased CD36 mRNA gene and protein expression.[2, 10] The study demonstrated that the antioxidant activity of hibiscus may inhibit the formation of oxidized LDL foam cells.[2]

SAFETY

Hibiscus has been used in at least 10 countries worldwide in a variety of forms including decoctions, infusions of calyxes, and as leaves for treating hypertension and hyperlipidemia, with no reported adverse events or side effects.[1] Hibiscus extracts have a low degree of toxicity, with estimated LD50 values in humans ranging from 2,000 to over 5,000 mg/kgbw/d. No evidence exists suggesting hepatic or renal toxicity from hibiscus extract consumption; however, very high doses of hibiscus may have possible adverse hepatic effects.[1]

REFERENCES

Hopkins, A.L., et al. “Hisibcus sabdariffa L. in the treatment of hypertension and hyperlipidemia: A comprehensive review of animal and human studies”. Fitoterapia Vol. 85 (2013): 84–94. Saunders, L. and P. Rouchotas. “Hibiscus — An emerging new botanical medicine”. IHP magazine (2013): 67–71. Ojeda, D., et al. “Inhibition of angiotensin converting enzyme (ACE) activity by the anthocyanins delphinidin- and cyaniding3-O-sambubiosides from Hibiscus sabdariffa”. Journal of Ethnopharmacology Vol. 127, No. 1 (2010): 7–10. 4. Frank, T., et al. “Pharmacokinetics of anthocyanidin-3-glycosides following consumption of Hibiscus sabdariffa L. extract”. Journal of Clinical Pharmacology Vol. 45, No. 2 (2005): 203–210. 5. Herrera-Arellano, A., et al. “Clinical effects produced by a standardized herbal medicinal product of Hibiscus sabdariffa on patients with hypertension. A randomized, double-blind, lisinopril-controlled clinical trial”. Planta Medica Vol. 73, No. 1 (2007): 6–12. 6. Herrera-Arellano, A., et al. “Effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa in patients with mild to moderate hypertension: a controlled and randomized clinical trial”. Phytomedicine Vol. 11, No. 5 (2004): 375–382. 7. Yang, M.Y., et al. “The hypolipidemic effect of Hibiscus sabdariffa polyphenols via inhibiting lipogenesis and promoting hepatic lipid clearance”. Journal of Agricultural and Food Chemistry Vol. 58, No. 2 (2010): 850–859. 8. Kuriyan, R., et al. “An evaluation of the hypolipidemic effect of an extract of Hibiscus sabdariffa leaves in hyperlipidemic Indians: a double blind, placebo controlled trial”. BMC Complementary and Alternative Medicine Vol. 10 (2010): 27–34. 9. Gurrola-Diaz, C.M., et al. “Effects of Hibiscus sabdariffa extract powder and prevention treatment (diet) on the lipid profiles of patients with metabolic syndrome (MeSy)”. Phytomedicine Vol. 17, No. 7 (2010): 500–505. 10. Kao, E.S., et al. “Anthocyanin extracted from Hibiscus attenuate oxidized LDL-mediated foam cell formation involving regulation of CD36 gene”. Chemico-Biological Interactions Vol. 179, No. 2–3 (2009): 212–218. 1. 2. 3.

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Hibiscus SAP

Science-based hibiscus for hypertension Hibiscus sabdariffa (hibiscus) is a medicinal botanical that maintains cardiovascular health, based on evidence from several clinical trials.[1] Hibiscus has a beneficial effect on blood pressure, blood sugar, and cholesterol, and has antioxidant properties.[1] This botanical has been used historically in both Asia and Africa as an aqueous extract or tea to treat high blood pressure, liver disease, and fevers.[2] Hibiscus possesses several active constituents, including anthocyanidins which are thought to be the source of its antioxidant effects.[1]

Each vegetable capsule contains:

ACTIVE INGREDIENTS

Hibiscus sabdariffa flower extract, 15% anthocyanidins . . . . . . . . . . . . . . . . . . . . . . . 600 mg

Contains no: Preservatives, artificial flavor or color, sugar, dairy, starch, wheat, gluten, yeast, soy, citrus, or eggs. Hibiscus SAP contains 90 capsules per bottle.

ADULT DOSAGE

1 capsule one to three times daily or as directed by your health care practitioner.

INDICATION

ɶ Hibiscus SAP assists in maintaining healthy blood pressure levels. ɶ Hibiscus SAP promotes healthy cholesterol levels. ɶ Hibiscus SAP supports healthy blood sugar levels.

CAUTIONS

Consult a health care practitioner prior to use if you are pregnant or breast-feeding. Hypersensitivity has been known to occur ; in which case, discontinue use.

PURITY, CLEANLINESS AND STABILITY

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

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

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

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2014-02-06 15:34:09 14-02-07 1:55 PM

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