IHP December 2014 by IHP Magazine

clinic profile

MUCOSITIS By Meighan Valero, ND

LIFESTYLE GENOMICS By Robyn Murphy, ND, et al.

MEDITATION AND GENE EXPRESSION

PM42684014 | 60 BLOOR STREET WEST SUITE 1106 | TORONTO ONTARIO, M4W 3B8 | $14.95

By Paulina Kapoustina, ND (Cand).

Project SOIL Using institutional

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DECEMBER 2014

Continuing Education Melatonin in Oncology By Jessa Landmann, ND 1

www.ihpmagazine.com | June/July 2014

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2014-12-18 12:11 PM

Restoring Microflora to a Healthy Balance

GENESTRA BRANDS Candaclear Four contains a potent combination of natural antimicrobial compounds along with a therapeutic dose of HMF probiotics to restore a naturally healthy gut flora. This 30 day therapy is provided in individual serrated strips (containing one tablet and three capsules) that deliver: • 25 billion CFU of human-sourced probiotics clinically proven to significantly reduce symptoms of irritable bowel syndrome

• N-acetyl glucosamine (NAG), L-glutamine, and β-carotene to help support digestive system health • Vitamin A to help maintain immune function • Cinnamon, which is traditionally used in Herbal Medicine to help relieve gastrointestinal complaints • Allicin, which has effective antimicrobial properties

GENESTRA BRANDS CANDACLEAR FOUR PRODUCT MONOGRAPH GENESTRA BRANDS Candaclear Four contributes to a naturally healthy gut flora using a unique combination of human-sourced probiotics, L-glutamine, allicin, cinnamon, n-acetyl glucosamine (NAG), L-glutamine, and vitamin A (from β-carotene). The human gut flora contains approximately 1014 bacteria, from more than 1000 different species.1 Some of these bacterials strains are known to exert a barrier effect on the intestinal mucosa that helps to protect against pathogens and maintain normal immune function.1 Disruption of healthy gut microbial composition, sometimes referred to as “dysbiosis”, is associated with irritable bowel syndrome (IBS) and other gastrointestinal disorders.2 Supplementation with probiotics has been clinically shown to relieve IBS symptoms3 and modulate intestinal microflora composition.4 The probiotic formulation used in Candaclear Four contains 25 billion CFU of human-sourced probiotics that are clinically proven to decrease IBS symptoms and number of days with pain, while improving satisfaction with bowel habits and overall quality of life.3 Allicin and cinnamon possess potent antimicrobial properties both in vitro and in vivo. In a double-blind clinical trial of 210 patients positive for Helicobacter pylori infection, 2 weeks of daily allicin supplementation increased the rate of H. pylori elimination when combined with standard antibiotic treatment protocols, compared to antibiotic therapy alone.5 Cinnamon (Cinnamomum verum), sometimes referred to as Cinnamomum zeylanicum, has shown antimicrobial effects against pathogenic bacteria in vitro6,7 and against several strains of Candida yeast in a recent human clinical trial of 60 Candida-infected patients.8 Cinnamon is also traditionally used in Herbal Medicine as a carminative to help relieve gastrointestinal complaints.9

Delayed Release Allicin

EACH CAPSULE CONTAINS: Garlic (Allium sativum) Bulb (providing 10 mg thiosulfinates and 4.5 mg allicin) . . . . . . . . . . . . . . . . . . . . . . . 500 mg Cinnamon (Cinnamomum verum) Bark Oil (providing 40 mg cinnamaldehyde) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 mg Cinnamon (Cinnamomum verum) Bark . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 mg

Allicin with caprylates

EACH TABLET CONTAINS: Garlic (Allium sativum) Bulb (providing 10 mg thiosulfinates and 4.5 mg allicin) . . . . . . . . . . . . . . . . . . . . . . . 500 mg

Allicin with cinnamon

L-glutamine and vitamin A have both been clinically shown to help maintain normal intestinal barrier function, by reducing intestinal barrier permeability. The intestinal epithelium is normally “selectively permeable”, allowing for the absorption of nutrients and water while acting as a barrier against the intestinal microflora.10 However, an overgrowth of pathogenic bacteria can cause increased intestinal barrier permeability.10 In a recent double-blind, placebo-controlled clinical trial of 120 children at increased risk of enteric illness, 10 days of glutamine supplementation alone or in combination with vitamin A and zinc significantly improved lactulose:mannitol intestinal barrier function test scores.11 In a similar clinical trial, supplementation with vitamin A and zinc was also found to improve intestinal barrier function test scores.12 Vitamin A also helps in the maintenance of the body’s membranes and immune function.13

Non-Medicinal Ingredients: Hypromellose, dicalcium phosphate, cellulose, magnesium stearate, silica, glycerin, titanium dioxide

Non-Medicinal Ingredients: Hypromellose, magnesium stearate, silica

EACH CAPSULE CONTAINS: Garlic (Allium sativum) Bulb (providing 4 mg thiosulfinates and 1.8 mg allicin) . . . . . . . . . . . . . . . . . . . . . . . . 200 mg Cinnamon (Cinnamomum verum) Bark Oil (providing 20 mg cinnamaldehyde) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 mg Non-Medicinal Ingredients: Magnesium caprylate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200 mg Calcium caprylate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 mg

Probiotic with nutrients

Other Non-Medicinal Ingredients: Hypromellose, magnesium stearate, silica

EACH CAPSULE CONTAINS: Probiotic Consortium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 billion CFU Lactobacillus acidophilus (CUL-60) Lactobacillus acidophilus (CUL-21) Bifidobacterium bifidum (CUL-20) Bifidobacterium animalis subsp. lactis (CUL-34) L-Glutamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .400 mg N-Acetyl Glucosamine (from exoskeleton of shrimp / crab) . . . . . . . . . . . . . . . . . .200 mg Beta-carotene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 mg

Recommended Adult Dose: One serrated strip, containing one tablet and three capsules, taken once daily with a meal, or as recommended by your healthcare practitioner. Take at least two to three hours before or after antibiotics. Risk Information: If you are pregnant or breastfeeding; or if you have stomach or duodenal ulcers, an immunecompromised condition or hypersensitivity to cinnamon or Peru balsam, do not use. If symptoms of digestive upset occur, worsen or persist beyond three days, discontinue use and consult your healthcare practitioner. If you have diabetes; if you are taking blood thinners or protease inhibitors; if you have nausea, fever, vomiting, bloody diarrhoea or severe abdominal pain, consult your healthcare practitioner prior to use. If symptoms persist or worsen, consult your healthcare practitioner. 30 Day Supply Product Number: 10577

Non-Medicinal Ingredients: Hypromellose, magnesium stearate, silica 1. Shim JO. Gut Microbiota in Inflammatory Bowel Disease. Pediatric Gastroenterology, Hepatology & Nutrition. 2013; 16: 17-21 2. Hong SN and Rhee PL. Unraveling the ties between irritable bowel syndrome and intestinal microbiota. World Journal of Gastroenterology. 2014; 20(10): 2470-2481 3. Williams E, Stimpson J, Wang D, Plummer S, Garaiova I, Barker M, and Corfe B. Clinical trial: a multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study. Alimentary Pharmacology & Therapeutics. 2008; 29: 97-103 4. Plummer S, Garaiova I, Sarvotham T, Cottrell S, Le Scouiller S et al. Effects of probiotics on the composition of the intestinal microbiota following antibiotic therapy. International Journal of Antimicrobial Agents. 2005; 26: 69-74 5. Koçkar C , Öztürk M and Bavbek N. Heliobacter Pylori Eradication with Beta Carotene, Ascorbic Acid and Allicin. Acta Medica (Hradec Králové) 2001; 44(3): 97-100 6. Naveed R, Hussain I, Tawab A, Tariq M, Rahman M et al. Antimicrobial activity of the bioactive components of essential oils from Pakistani spices against Salmonella and other multi-drug resistant bacteria. BMC Complementary and Alternative Medicine. 2013; 13: 265 7. Ranasinghe P, Pigera S, Premakumara GA, Galappaththy P, Constantine G, Katulanda P. Medicinal properties of ‘true’ cinnamon (Cinnamomum zeylanicum): a systematic review. BMC Complementary and Alternative Medicine 2013, 13:275 8. Wang GS, Deng JH, MA YH and Shi M. Mechanisms, clinically curative effects, and antifungal activities of cinnamon oil and pogostemon oil complex against three species of Candida. J Traditional Chinese Medicine. 2012; 32(1): 1-2 9. NHPD Monograph on Cinnamon - Cinnamomum verum. February 2013 10. Groschwitz K and Hogan S. Intestinal barrier function: Molecular regulation and disease pathogenesis. Journal of Allergy and Clinical Immunology. 2009;124(1): 3-20 11. Lima A, Anstead G, Zhang Q, Figueiredo I, Soares A et al. Effects of glutamine alone or in combination with zinc and vitamin A on growth, intestinal barrier function, stress and satiety-related hormones in Brazilian shantytown children. Clinics. 2014; 69(4): 225-233 12. Chen P, Soares AM, Lima AA, Gamble MV, Schorling JH et al. Association of vitamin A and zinc status with altered intestinal permeability: analyses of cohort data from northeastern Brazil. Journal of Health Population and Nutrition. 2003; (4): 309-15 13. NHPD Monograph on Vitamin A. March 2010

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from the publisher

Happy Holidays New years brings us new beginnings as we put another year behind us! As an industry we look forward to seeing more mergers, and new innovative companies emerging. Technology and personalization will play a big role… Consumers are truly looking for personalized attention, not to be made to feel like one of the masses. Devices targeting personalized health monitoring seem to be making a strong push… The early adaptors already have these devices on their person, in their homes, even in their cars! What can’t be replaced is the one on one personal human interaction. We must constantly remind ourselves all this technology is to free us up to spend more time with one another and not to become self- absorbed! Personal interaction is where true healing begins… technology can only do so much! Happy Holidays! Happy New Year! Sanjiv Jagota Publisher

Connect With Us

www.ihpmagazine.com | December 2014

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

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

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contents

This Issue: December 2014 • Vol. 7 • No. 6

38 Project SOIL

Cover Story Food Production at Health Care Institutions

Centre of Naturopathic 44 Marsden Excellence Clinic Profile

Leading Integrative Oncology

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

Coming Next Issue Nucleotide therapy in Alzheimer’s and Hepatitis C Clinical outcomes of meditation Ginkgo - a review Cover Photograph by Christine Kufske 8

www.ihpmagazine.com | December 2014

Departments

4 Publisher’s Letter 11 Research News 23 Industry News 29 Calendar 32 Product Profiles 51 Editor’s Letter 53 Peer Review Board 55 Editorial Board 74 Continuing Education

Paleolithic Nutrition. Timeless.

Paleo Product Family

Now in Canada Leaders in Education â&#x2014;ź Innovative Professional Formulas 877-414-9388 www.designsforhealth.ca PaleoCompleteDF profile.indd 1

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PaleoComplete-DF - Monograph Description: PaleoComplete-DF® is a great-tasting, nutrient-rich powdered meal supplement designed to help promote an optimal intake of protein, fats, carbohydrates, vitamins and minerals needed for overall wellness. In alignment with the principles of the Paleolithic Diet, this formula is ideal to support weight control, GI health, detoxification, immune issues, heavy metals, and muscle gain. Available in delicious Berry and Vanilla flavours, PaleoComplete-DF® is dairy-free and plant-derived, featuring a natural pea protein isolate as its protein source. This formula is casein-free, lactose-free and gluten-free and includes a comprehensive blend of added nutrients to promote health and healing. Benefits: PaleoComplete-DF® includes a comprehensive array of plant-based enzymes for proper digestion, including lactase, amylase and proteases, along with L-glutamine to provide energy for intestinal enterocytes, lymphocytes, macrophages and fibroblasts and to maintain intestinal lining integrity. Chromium, in combination with biotin, has been shown in randomized double-blind placebo-controlled trials to reduce both HbA1c and fasting glucose levelsi. Inositol promotes efficient uptake of glucose by increasing intracellular insulin action while CLA has been shown to decrease energy intake, increase total energy expenditure, and regulate adipogenesis while stimulating lipolysisii. PaleoComplete-DF® includes the prebiotic fiber inulin, which subtly sweetens without affecting blood sugar levels. This soluble fiber is shown to protect against metabolic syndrome by controlling blood lipids and blood glucose while supporting GI health by modulating gut microbiota. Inulin dissolves easily in water, making PaleoComplete-DF® very easy to mix and creates an ultra-smooth texture. PaleoComplete-DF® contains hypoallergenic Pea Protein isolate from non-GMO North American peas produced by a natural fermentation process which uses no chemical solvents. This protein has high bioavailability and digestability, providing 17g of protein per serving. The folate included in this formula is found in foods such as eggs and spinach and, in its active form, is immediately bioavailable to the human body. Creatine included in PaleoComplete-DF® plays an important role in the maintenance and regeneration of ATP, and helps to increase muscle mass, strength and endurance. PaleoComplete-DF® contains 840 mg of phosphatidylcholine per serving; since liver cell membranes comprise of phosphatidylcholine, it is a critically important nutrient for liver support. Supporting the liver is important when working with toxic chemicals, living in a polluted area, taking prescription or over the counter medications, or with any form of hepatitis. Medicinal Ingredients (per scoop): Taurine (2-Aminoethanesulfonic acid) 100 mg Niacinamide (3-Pyridinecarboxamide) 10 mg Alpha-Amylase (4-alpha-D-Glucan glucanohydrolase Aspergillus flavus var. oryzaeWhole) 50 mg/2200 FCC DU Biotin 100 mcg Pantothenic Acid 100 mg Chromium 50 mcg CLA (Conjugated linoleic acid) 120 mg Folate (Brassica oleracea var. italica-Herb top) 100 mcg L-Glutamine 900 mg

research news

Pain management with acupuncture in osteoarthritis

Urinary sodium and potassium excretion, mortality, and cardiovascular events In this study, the authors examined the association between urinary sodium and potassium excretion and the outcomes of death and major cardiovascular events. Morning fasting urine samples from 101,945 persons in 17 countries were obtained and estimated 24-hour sodium and potassium excretion as well (used as a surrogate for intake). The results showed that mean estimated sodium and potassium excretion was 4.93 g per day and 2.12 g per day, respectively. With a mean follow-up of 3.7 years, the composite outcome occurred in 3317 participants (3.3%). As compared with an estimated sodium excretion of 4.00 to 5.99 g per day (reference range), a higher estimated sodium excretion (≥ 7.00 g per day) was associated with an increased risk of the composite outcome (odds ratio, 1.15; 95% confidence interval [CI], 1.02 to 1.30), as well as increased risks of death and major cardiovascular events considered separately. The authors conclude that an estimated sodium intake between 3 g per day and 6 g per day was associated with a lower risk of death and cardiovascular events than was either a higher or lower estimated level of intake. As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a lower risk of death and cardiovascular events. N Engl J Med. 2014. PMID: 25119607

In this systematic review and meta-analysis, the authors analyzed the utility of acupuncture in managing osteoarthritis symptoms. Two reviewers independently identified randomized controlled trials (up to May 2014) from multiple electronic sources (including PubMed/Medline, EMBASE, and CENTRAL) and reference lists of relevant articles, extracted data and assessed risk of bias (Cochrane's Risk of Bias tool). Pooled data are expressed as mean differences (MD), with 95% confidence intervals (CI) (random-effects model). The results showed that 12 trials were included (1763 participants) comparing acupuncture to sham acupuncture, no treatment or usual care. Acupuncture use was associated with significant reductions in pain intensity (MD -0.29, 95% CI -0.55 to -0.02, I2 0%, 10 trials, 1699 participants), functional mobility (standardized MD -0.34, 95% CI -0.55 to -0.14, I2 70%, 9 trials, 1543 participants), health-related quality of life (standardized MD -0.36, 95% CI -0.58 to -0.14, I2 50%, 3 trials, 958 participants). Subgroup analysis of pain intensity by intervention duration suggested greater pain intensity reduction with intervention periods greater than 4 weeks (MD -0.38, 95% CI -0.69 to -0.06, I2 0%, 6 trials, 1239 participants). The authors conclude that acupuncture is associated with significant reductions in pain intensity, improvement in functional mobility and quality of life. BMC Complement Altern Med. 2014. PMID: 25151529

Physical activity for cognitive decline in postmenopausal women In this study, the authors reviewed research on the impact of leisure-time and general physical activity levels on physical and cognitive decline in postmenopausal women. In a systematic review of the literature, empirical literature from 2009 to 2013 is reviewed to explore the potential impact of either commencing or sustaining physical activity on older women’s health. The results showed that all studies found that physical activity was associated with lower rates of cognitive and physical decline and a significant reduction in all-cause mortality. They found that exercise interventions (or lifestyle activities) that improved cardiorespiratory exercise capacity showed the most positive impact on physical health. The authors conclude that programs should facilitate and support women to participate in regular exercise by embedding physical activity programs in public health initiatives, by developing home-based exercise programs that require few resources and by creating interventions that can incorporate physical activity within a healthy lifestyle. The review also suggests that clinicians should consider prescribing exercise in a tailored manner for older women to ensure that it is of a high enough intensity to obtain the positive sustained effects of exercise. Maturitas. 2014. PMID: 25008420. December 2014 | www.ihpmagazine.com

research news Comparison of weight loss among named diet programs In this meta-analysis, the authors attempted to determine weight loss outcomes for popular diets based on diet class (macronutrient composition) and named diet. They searched 6 electronic databases: AMED, CDSR, CENTRAL, CINAHL, EMBASE, and MEDLINE from inception of each database to April 2014. The studies selected included overweight or obese adults (body mass index ≥25) randomized to a popular self-administered named diet and reporting weight or body mass index data at 3-month follow-up or longer. The results showed that among 59 eligible articles reporting 48 unique randomized trials (including 7286 individuals) and compared with no diet, the largest weight loss was associated with low-carbohydrate diets (8.73 kg [95% credible interval {CI}, 7.27 to 10.20 kg] at 6-month follow-up and 7.25 kg [95% CI, 5.33 to 9.25 kg] at 12-month follow-up) and low-fat diets (7.99 kg [95% CI, 6.01 to 9.92 kg] at 6-month follow-up and 7.27 kg [95% CI, 5.26 to 9.34 kg] at 12-month follow-up). Weight loss differences between individual diets were minimal. Between 6and 12-month follow-up, the influence of behavioral support (3.23 kg [95% CI, 2.23 to 4.23 kg] at 6-month follow-up vs 1.08 kg [95% CI, -1.82 to 3.96 kg] at 12-month followup) and exercise (0.64 kg [95% CI, -0.35 to 1.66 kg] vs 2.13 kg [95% CI, 0.43 to 3.85 kg], respectively) on weight loss differed. The authors conclude that significant weight loss was observed with any low-carbohydrate or low-fat diet. JAMA. 2014. PMID: 25182101

Low vitamin D associated with insulin resistance in those with lupus In this study, the authors examined if there is an association between low levels of 25-hydroxyvitamin D (25(OH)D) and insulin resistance (IR) in nondiabetic women with systemic lupus erythematosus (SLE) and to evaluate its impact on arterial stiffness. The results showed that women with SLE tended to have lower 25(OH)D levels (p = 0.078) and a higher frequency of 25(OH)D deficiency (defined as <10 ng/ml) than controls (p = 0.058). Patients from the lowest quartile of the 25(OH)D range had higher PWV (p = 0.043), fasting glucose (p = 0.035), insulinemia (p ≤ 0.001), HOMAIR (p = 0.006), C4 (p = 0.012), as well as more frequent IR (p = 0.002) and metabolic syndrome (p = 0.052) than those in the upper quartile, and no differences were found in age, body mass index (BMI), blood pressure, lipid levels and renal function. In women with SLE, 25(OH)D inversely correlated with insulin (p = 0.006), HOMA-IR (p = 0.008) and C4 (p = 0.048) and tended to correlate with fibrinogen (p = 0.060) after adjustment for BMI, age, SLEDAI, prednisone dose, renal function, inflammation markers and seasonal variation, but not with PWV. The authors conclude that low 25(OH)D levels were found to be associated with increased IR in nondiabetic women with SLE independently of BMI. Low 25(OH)D levels, but not IR, could be associated with increased arterial stiffness in these patients. Lupus. 2014. PMID: 25216653. 12

www.ihpmagazine.com | December 2014

Sesbania grandiflora neuroprotective against oxidative stress In this study, the authors evaluated the neuroprotective role of Sesbania grandiflora (S. grandiflora) against chronic cigarette smoke induced oxidative damage in rat brain. Adult male Wistar-Kyoto rats were exposed to cigarette smoke for a period of 90 days and consecutively treated with S. grandiflora aqueous suspension (SGAS, 1,000 mg/kg body weight per day by oral gavage) for a period of 3 weeks. Lipid peroxidation and antioxidants status were analyzed in the brain. The results showed that rats exposed to cigarette smoke showed significant increase in conjugated diens (CD), hydroperoxides (HP) and malendialdehyde (MDA) levels with concomitant decrease in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) activities and the levels of reduced glutathione (GSH), vitamin C and vitamin E. Also cigarette smoke-exposure resulted in a marked increase in copper and decrease in zinc, manganese and selenium levels in brain. Administration of SGAS attenuates lipid peroxidation, enhanced the antioxidant status, restored the levels of micronutrients and retained the brain histology. The authors conclude that chronic cigarette smoke-exposure accelerates oxidative stress, thereby disquieting the brain defensive mechanism and S. grandiflora protects the brain from the oxidative damage through its biopotency. Metab Brain Dis. 2014. PMID: 25217401

Response rate of patients [Percent of patients] 80

p = 0.4928

30 20 10 0

Run-InPhase

-1

Therapy-Phase

0 1 2 3

*significant *** highly significant (Mann-Whitney Test) (Responder: either HAMD21 score of <10, or 50% decrease in score)

NEURAPAS速 balance p = 0.0024* p = 0.0001***

Placebo

p = 0.0001***

6 Week

research news Correcting for low vitamin D improves fatigue: EViDiF Study

Vitamin D status and risk of Dementia In this study, the authors investigated whether serum 25-hydroxyvitamin D (25(OH)D) level predicts dementia risk, as high vitamin D status has been hypothesized to protect against it. The study was based on the Mini-Finland Health Survey. The study population consisted of 5010 men and women, aged 40-79 years, and free of dementia at baseline. During a 17-year follow up, 151 incident cases of dementia (International Classification of Diseases, revision 8, code 290) occurred, according to population registers. Serum 25(OH)D concentration was determined from serum samples frozen at -20°C and stored at baseline. The results showed that among women, these with higher serum 25(OH)D concentrations showed a reduced risk of dementia. The hazard ratio between the highest and lowest quartiles of serum 25(OH)D was 0.33 (95% confidence interval = 0.15-0.73) in women and 0.74 (0.29-1.88) in men, after adjustment for age, month of blood draw, education, marital status, physical activity, smoking, alcohol consumption, body mass index, blood pressure, plasma fasting glucose, serum triglycerides, and serum total cholesterol. The authors conclude that low vitamin D status may be a risk factor for dementia. Epidemiology. 2014. PMID: 25215530.

This prospective non-randomized therapeutic study observed the prevalence of low vitamin D in fatigue and the effect of normalization of vitamin D on fatigue. Fatigue is a common presenting complaint of patients in the primary care offices. Low levels of vitamin D have been associated with fatigue in cancer patients. Normalization of vitamin D level improves their fatigue. Whether low vitamin D plays a role in fatigue in medically stable patients is not known. One hundred and seventy four adult patients, who presented in our primary care office with fatigue and stable chronic medical conditions, completed fatigue assessment questionnaires. Patients with low vitamin D levels received ergocalciferol therapy for 5 weeks. Scores of pre- and posttreatment fatigue assessment questionnaires were compared. The results showed that prevalence of low vitamin D was 77.2% in patients who presented with fatigue. After normalization of vitamin D levels fatigue symptom scores improved significantly (P < 0.001) in all five subscale categories of fatigue assessment questionnaires. The authors conclude that the prevalence of low vitamin D is high in patients who present with fatigue and stable chronic medical conditions, if any. Normalization of vitamin D levels with ergocalciferol therapy significantly improves the severity of their fatigue symptoms. N Am J Med Sci. 2014. PMID: 25210673

Saccharomyces boulardii in the treatment and prevention of antibiotic-associated diarrhea In this review, available studies on S. boulardii in the prevention of AAD were presented. Antibiotic-associated diarrhea (AAD) is the most frequent side effect of antibiotic therapy. Clinical signs and symptoms comprise mild and self-limiting courses of diarrhea as well as life threatening courses like pseudomembranous colitis or toxic megacolon. Therapy is symptomatic, antidiarrheal drugs like Saccharomyces boulardii are the therapy of choice. The result showed that in 14 out of 17 studies including 4,627 patients the administration of S. boulardii achieved a protective effect between 43.7% and 87.3%. A meta-analysis (5 studies, 1,076 patients) showed a significant reduction of the risk to develop an AAD from 17.2% to 6.7%,in a further meta-analysis (4 studies on eradication of H. pylori, 1,215 patients) the significant reduction was from 12.2% to 5.6%. The authors conclude that there is very good evidence for the yeast S. boulardii to be effective in the prevention of AAD especially in hospitalized adults. The simultaneous administration of S. boulardii to antibiotics resulted in a significant reduction to develop AAD by more than half. MMW Fortschr Med. 2014. PMID: 24930328. December 2014 | www.ihpmagazine.com

research news

LDL cholesterol: controversies and future therapeutic directions In this article, LDL cholesterol is discussed. Lifelong exposure to raised concentrations of LDL cholesterol increases cardiovascular event rates, and the use of statin therapy as an adjunct to diet, exercise, and smoking cessation has proven highly effective in reducing the population burden associated with hyperlipidaemia. There is controversy among national guidelines and clinical practice with regard to LDL cholesterol, its measurement, the usefulness of population-based screening, the net benefit-to-risk ratio for different LDL-lowering drugs, the benefit of treatment targets, and whether aggressive lowering of LDL is safe. Several novel therapies have been introduced for the treatment of people with genetic defects that result in loss of function within the LDL receptor, a major determinant of inherited hyperlipidaemias. Moreover, the usefulness of monoclonal antibodies that extend the LDL-receptor lifecycle (and thus result in substantial lowering of LDL cholesterol below the levels achieved with statins alone) is being assessed in phase 3 trials that will enrol more than 60,000 at-risk patients worldwide. These trials represent an exceptionally rapid translation of genetic observations into clinical practice and will address core questions of how low LDL cholesterol can be safely reduced, whether the mechanism of LDL-cholesterol lowering matters, and whether ever more aggressive lipid-lowering provides a safe, long-term mechanism to prevent atherothrombotic complications. Lancet. 2014. PMID: 25131980.

Lactobacillus reuteri RCT for infant colic In this study, 167 breastfed infants or formula fed infants aged less than 3 months meeting Wessel’s criteria for crying or fussing: 85 were randomised to receive probiotic and 82 to receive placebo. The probiotic treatment was oral daily L reuteri (1 × 10(8) colony forming units) versus placebo for one month. The results showed that of 167 infants randomised from August 2011 to August 2012, 127 (76%) were retained to primary outcome; of these, a subset was analysed for faecal microbial diversity, E coli colonisation, and calprotectin levels. Adherence was high. Mean daily cry or fuss time fell steadily in both groups. At 1 month, the probiotic group cried or fussed 49 minutes more than the placebo group (95% confidence interval 8 to 90 minutes, P=0.02); this mainly reflected more fussing, especially for formula fed infants. The groups were similar on all secondary outcomes. No study related adverse events occurred. The authors conclude that L reuteri DSM 17938 did not benefit a community sample of breastfed infants and formula fed infants with colic. These findings differ from previous smaller trials of selected populations and do not support a general recommendation for the use of probiotics to treat colic in infants. BMJ. 2014. PMID: 24090625. 16

www.ihpmagazine.com | December 2014

RCT of Bididobacterium in children with coeliac disease In this study, the potential effects of Bifidobacterium longum CECT 7347 in children with newly diagnosed CD were evaluated. A double-blind, randomised, placebo-controlled trial was conducted in thirty-three children who received a capsule containing either B. longum CECT 7347 (10⁹ colony-forming units) or placebo (excipients) daily for 3 months together with a gluten-free diet (GFD). The results showed that comparisons between the groups revealed greater height percentile increases (P= 0·048) in the B. longum CECT 7347 group than in the placebo group, as well as decreased peripheral CD3+ T lymphocytes (P= 0·004) and slightly reduced TNF-α concentration (P= 0·067). Within-group comparisons of baseline and final values did not reveal any differences in T lymphocytes and cytokines in the placebo group, while decreased CD3+ (P =0·013) and human leucocyte antigen (HLA)-DR+ T lymphocytes (P =0·029) and slightly reduced TNF-α concentration (P= 0·085) were detected in the B. longum CECT 7347 group. Comparison between the groups showed that the administration of B. longum CECT 7347 reduced the numbers of the Bacteroides fragilis group (P= 0·020) and the content of sIgA in stools (P= 0·011) compared with the administration of placebo. Br J Nutr. 2014. PMID: 24774670.

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.

research news Interprofessional education: merging nursing, midwifery and CAM

Exercise improves erectile dysfunction in those with metabolic syndrome Phosphodiesterase-5 inhibitors are well known pharmacologic agents capable of significant improvement in ED, so the authors designed this study to evaluate whether exercise training is of added value in patients with ED who are already on PDE-5 inhibitors. They recruited 20 male patients affected by ED with metabolic syndrome. At baseline, all patients underwent CardioPulmonary Exercise Testing (CPET) and the International Index of Erectile Function (IIEF) test. After the initial evaluation, patients were subdivided into two groups: tadalafil group (group T, n = 10), who were maintained only on tadalafil therapy, and a tadalafil/ exercise training group (T/E group, n = 10). The results showed that although both-groups showed at 2 months an improvement of the IIEF score, this was more evident in the T/E group. There was an improvement of oxygen consumption at peak exercise (VO(2peak)) only in the T/E group patients. A significant correlation was found between the changes in VO(2peak) and the modifications in IIEF score (r = 0.575; P = 0.001). The authors conclude that exercise training in ED patients treated with PDE-5 inhibitors is of added value since further improves ED, as evaluated by IIEF score, and increases functional capacity. Monaldi Arch Chest Dis. 2013. PMID: 25087294.

In this study, the authors evaluated the value of bringing together undergraduate students from nursing, midwifery, and complementary and alternative medicine (CAM) to determine what they could learn from each other. Interprofessional education (IPE) is a growing field promoting interaction between professional groups, collaborative working and quality of health. In conventional health, IPE has a role to play in undergraduate education. No studies have been undertaken to investigate the integration of CAM students and conventional undergraduate healthcare students. In a mixed-method study, in 2010, a sample of third-year students enrolled on adult nursing, midwifery, homeopathy and complementary therapies degree courses took part in two workshops and a focusgroup discussion. The results showed that six themes were identified from qualitative data analysis: interaction; breaking down prejudices; knowledge of self; knowledge of others; common aims; and organizational limitations. The authors conclude that the common aim of patient-centred care allowed students to recognize the benefits of a more integrated health system. Br J Nurs. 2014. PMID: 25072337.

Cranberry capsules for urinary tract infections: RCT In this study, the authors tried to determine whether cranberry capsules prevent urinary tract infection (UTI) in long-term care facility (LTCF) residents. It was a double-blind randomized placebo-controlled multicenter trial. The participants were LTCF residents (N = 928; 703 women, median age 84). Cranberry and placebo capsules were taken twice daily for 12 months. Participants were stratified according to UTI risk (risk factors included long-term catheterization, diabetes mellitus, ≥ 1 UTI in preceding year). Main outcomes were incidence of UTI according to a clinical definition and a strict definition. The results showed that in participants with high UTI risk at baseline (n = 516), the incidence of clinically defined UTI was lower with cranberry capsules than with placebo (62.8 vs 84.8 per 100 person-years at risk, P = .04); the treatment effect was 0.74 (95% confidence interval (CI) = 0.57-0.97). For the strict definition, the treatment effect was 1.02 (95% CI = 0.68-1.55). No difference in UTI incidence between cranberry and placebo was found in participants with low UTI risk (n = 412). The authors conclude that in LTCF residents with high UTI risk at baseline, taking cranberry capsules twice daily reduces the incidence of clinically defined UTI, although it does not reduce the incidence of strictly defined UTI. No difference in incidence of UTI was found in residents with low UTI risk. J Am Geriatr Soc. 2014. PMID: 25180378. December 2014 | www.ihpmagazine.com

research news Effect of self-monitoring and medicating for blood pressure: TASMIN-SR RCT This study examined self-monitoring and self-titration of antihypertensives in a high risk group. A primary care, unblinded, randomized clinical trial involving 552 patients who were aged at least 35 years with a history of stroke, coronary heart disease, diabetes, or chronic kidney disease and with baseline blood pressure of at least 130/80 mm Hg being treated at 59 UK primary care practices was conducted. Self-monitoring of blood pressure combined with an individualized self-titration algorithm. Control patients received usual care consisting of seeing their health care clinician for routine blood pressure measurement and adjustment of medication if necessary. The results showed that the mean baseline blood pressure was 143.1/80.5 mm Hg in the intervention group and 143.6/79.5 mm Hg in the control group. After 12 months, the mean blood pressure had decreased to 128.2/73.8 mm Hg in the intervention group and to 137.8/76.3 mm Hg in the control group, a difference of 9.2 mm Hg (95% CI, 5.7-12.7) in systolic and 3.4 mm Hg (95% CI, 1.8-5.0) in diastolic blood pressure following correction for baseline blood pressure. The authors conclude that among patients with hypertension at high risk of cardiovascular disease, selfmonitoring with self-titration of antihypertensive medication compared with usual care resulted in lower systolic blood pressure at 12 months. JAMA. 2014. PMID: 25157723

Adequate vitamin D levels lowers HbA1c in African American patients In this study, the authors examined the long-term effects of enhanced Vitamin D (VitD) supplementation on parameters of type 2 diabetes mellitus (T2DM): serum hemoglobin A1c, low density lipoprotein, high density lipoprotein, and triglyceride for the purpose of determining beneficial VitD levels in T2DM African Americans (AA). Following inclusion criteria, retrospective charts of patients aged > or = 30 years were reviewed. VitD supplementation was given to patients as part of drug regimen over a three year continuum. Pearson correlations were used to assess the relationship between VitD levels and levels of each parameter. Repeated measure analysis of variance was conducted to identify difference in mean levels of each parameter between years with VitD included as part of therapy. The results showed that Vitamin D supplementation was inversely associated with HbA1c (r = -.286, P = .031). No correlation was found between levels of VitD and levels of LDL, HDL or TG. The authors conclude that in T2DM AA, significant improvements in HbA1c are obtained with enhanced VitD supplementation as part of drug regimen over time. Ethn Dis. 2014. PMID: 25065076 20

Long-term colorectal-cancer mortality after adenoma removal In this study, mortality after adenoma removal was examined. Using the linkage of the Cancer Registry and the Cause of Death Registry of Norway, the authors estimated colorectal cancer mortality among patients who had undergone removal of colorectal adenomas during the period from 1993 through 2007. The results showed an identified 40,826 patients who had had colorectal adenomas removed. During a median follow-up of 7.7 years (maximum, 19.0), 1273 patients were given a diagnosis of colorectal cancer. A total of 398 deaths from colorectal cancer were expected and 383 were observed, for an SMR of 0.96 (95% confidence interval [CI], 0.87 to 1.06) among patients who had had adenomas removed. Colorectalcancer mortality was increased among patients with high-risk adenomas (expected deaths, 209; observed deaths, 242; SMR, 1.16; 95% CI, 1.02 to 1.31), but it was reduced among patients with low-risk adenomas (expected deaths, 189; observed deaths, 141; SMR, 0.75; 95% CI, 0.63 to 0.88). The authors conclude that after a median of 7.7 years of follow-up, colorectal-cancer mortality was lower among patients who had had low-risk adenomas removed and moderately higher among those who had had highrisk adenomas removed, as compared with the general population. N Engl J Med. 2014. PMID: 25162886

www.ihpmagazine.com | December 2014

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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.

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

industry news GENESTRA BRANDS™ Launches Statin Care GENESTRA BRANDS™ a trusted Seroyal® brand offering safe, effective, and reliable natural health products backed by clinical and traditional evidence, is proud to announce the release of Genestra Brands™ Statin Care, a balanced nutritional supplement formulated to provide nutritional support for patients taking statin medications. Statins are a common class of drugs used to treat high cholesterol levels: in 2012, over 38 million prescriptions for statins were filled in Canada. Statins work by inhibiting the enzyme HMG-CoA, which is needed to form both cholesterol and CoQ10, an antioxidant found in muscle cells. As many as 20% of patients taking statins experience muscle pain, which may be caused in part by decreased CoQ10 levels associated with statin usage. Genestra™ Statin Care combines CoQ10, L-carnitine and vitamin D in a convenient capsule format. Several human clinical trials conducted on patients taking statins have demonstrated that CoQ10 may help in reducing muscle pain symptoms, and L-carnitine may help to further decrease certain cardiovascular disease risk factors. "The combination of the three active ingredients in Genestra Brands™ Statin Care provide support for cardiovascular health," stated Dr. George Tardik, ND, a member of the Seroyal® Clinical Advisory Board and the developer of Statin Care. "Clinical study results lead us to believe these nutritional ingredients represent an excellent adjunct to statin treatment." In a double-blind, placebo-controlled clinical trial on 60 patients with muscle pain caused by statin use conducted in 2013 by Fedacko et al., daily supplementation with CoQ10 for three months resulted in a significant decrease in muscle pain, muscle weakness, and cramps, when compared to the placebo treatment group. In a clinical trial on 75 diabetic patients conducted in 2009 by Galvano et al., daily supplementation with L-carnitine and the statin drug simvastin was found to be more effective in improving cardiovascular disease risk factors than taking simvastin alone. After four months, the participants that received both L-carnitine and

simvastin had a significant decrease in lipoprotein(a), LDL cholesterol, and triglycerides when compared to the simvastin-only treatment group. After a rigorous review process, Health Canada's Natural Health Products Department (NHPD) has approved the claim: "helps to maintain and support cardiovascular health," for the new Statin Care formula. "Statin Care's formulation is our first formulation to combine these ingredients to support cardiovascular health at clinically effective doses," said Yves Yau, President at Seroyal. "Our mission is to offer healthcare practitioners and consumers the most researched and effective formulas to support overall health."

Blood inventory in critical condition Canadian Blood Services launches urgent appeal for donors Canadian Blood Services is appealing to all eligible donors to make a blood donation immediately to increase Canada's critically low blood inventory. All blood donors are needed, in particular those with type O and A blood. "Without the help of Canadians we may have difficulty meeting the expected hospital demand across the country. For patients, this may mean deferring elective or routine treatments," says Mark Donnison, Canadian Blood Services vice-president of donor relations. "We are committed to doing everything that we can to bring new blood donors into the system and encourage current donors to regularly donate to ensure we don't find ourselves in the same situation in the future." In recent months extremely low attendance at blood donor clinics across Canada in combination with the constant need for blood has caused the national inventory to be used faster than it can be replenished. This has created the lowest national blood inventory since 2008. "While we are extremely concerned that the reduced availability of blood may result in delays in treatment for certain patients, we are confident in the work Canadian Blood Services is doing, in collaborating with healthcare authorities to ensure patient safety," says Lorna Warwick, the Leukemia & Lymphoma Society of Canada senior national director. "We are calling on Canadians to donate blood today to ensure our system can help patients tomorrow." Canadian Blood Services is working closely with its partners within provincial and territorial health systems to ensure the safe, optimal and equitable supply of blood and blood products.

Government of Canada takes action to protect youth from dangers of tobacco use The Honourable Rona Ambrose, Minister of Health, announced new proposed regulatory amendments that would further restrict flavoured tobacco products that appeal to youth. Canada was the first country in the world to take action on ''little cigars" in 2010 when The Cracking Down on Tobacco Marketing Aimed at Youth came into force, banning the use of flavoured additives that contributed to making cigarettes, little cigars and blunt wraps more appealing to youth. Unfortunately, tobacco companies have skirted the law and found a "loophole" through the introduction of new cigars in the same "kiddie" flavours as those that were on the market before the 2009 law, merely changing the weight or removing filters. The proposed changes would close this loophole. Tobacco use is the leading preventable cause of death and disease in Canada, responsible for more than 37,000 deaths each year. The direct health care costs of smoking and other tobacco uses are estimated at $4.4 billionannually, and the total burden to the economy including indirect costs (e.g. lost wages, productivity) is estimated at$17 billion per year. Minister Ambrose is a strong advocate to end smoking, especially among our youth. Young Canadians continue to use flavoured tobacco products, including flavoured cigars. A formal 30-day consultation period will begin when a Notice describing the proposed amendments is published inCanada Gazette, Part I on October 10, 2014. Interested stakeholders are encouraged to submit their comments on the proposal online or via regular mail during the consultation period. Due to a lack of evidence on the benefits or harms of e-cigarettes, Minister Ambrose announced that she is asking the Standing Committee on Health to study the potential risks and benefits of e-cigarettes and to seek the advice of a variety of health stakeholders. December 2014 | www.ihpmagazine.com

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industry news Banting & Best Diabetes Centre Unveils Guidebook for Pharmacists on Diabetes Management Today, the Banting & Best Diabetes Centre (BBDC), Canada's leading centre of excellence for innovation in diabetes research, education and clinical care, unveils its Guidebook for Pharmacists on Diabetes Management through its Knowledge Translation and Optimizing Care Models Program. The launch signifies a demonstration of ongoing thought leadership and commitment to the diabetes community in supporting optimal medication management. Further, the BBDC is also announcing the launch of the Diabetes Pharmacists Network as a way to bring together pharmacists from across Canada interested in the care of patients with diabetes. Currently, one in four Canadians lives with diabetes, undiagnosed diabetes, or prediabetes and this number is expected to increase to one in three by 2020 if trends continue. Given the steadily increasing rates, the Guidebookprovides pharmacists a comprehensive but easy to use resource for supporting optimal patient education and decisions regarding diabetes. Its contents focuses on three areas of primary importance for effective diabetes management and care; glycemic management, cardiovascular protection and lifestyle modification. "Pharmacists are highly accessible health care providers who are on the front line, helping patients make decisions every day," says Dr. Lori MacCallum, BScPhm, PharmD, Program Director, Knowledge Translation and Optimizing Care Models, Banting & Best Diabetes Centre and Editor-in-Chief of the Guidebook and Sun Life Financial Professor of Wellness and Diabetes Education. "The goal of the Guidebook is to ensure all pharmacists have access to a comprehensive resource that's focused on treatment goals for people living with diabetes and how to help individuals achieve each goal. It also focuses on effective approaches to support patient education." People with diabetes see community pharmacists more than any other health care provider. As such, pharmacists across Canada are in a unique position to ensure that their scientific knowledge, and ability to translate that knowledge into action, helps to improve the lives of those living with diabetes. Further, and in recognizing the value of pharmacists in improving outcomes for patients while empowering and supporting those who exemplify best practices through networking, education, and knowledge translation initiatives, the Diabetes Pharmacists Network will be open to all licensed pharmacists in Canada interested in diabetes care.

Canadians Unaware Of How To Protect Against Travellers’ Diarrhea Ninety-four per cent of Canadians are unaware they can get sick from contaminated ice cubes while on vacation. Up to 70 per cent of travellers may experience travellers’ diarrhea while on vacation, the most common travel-related disease. However, a recent survey has revealed the majority of Canadians (79%) are not as travel savvy as they should be about the potential causes, symptoms and risks of an E. coli infection. Bacterial pathogens, such as enterotoxigenic E. coli (ETEC), are thought to cause approximately 80 per cent of cases of travellers’ diarrhea, which is characterized by a sudden onset of symptoms including watery diarrhea, fever, nausea, vomiting, and abdominal pain. ETEC is the leading bacteria causing up to one third of travellers’ diarrhea cases. “The effects of travellers’ diarrhea can be very serious, especially for children and older adults,” says Dr. Richard Fedorak, President of the Canadian Digestive Health Foundation. “Diarrhea caused by an E.coli infection is uncomfortable, inconvenient and can lead to severe dehydration which can be life-threatening. Knowing how to manage food and water intake, being sure to wash your hands before eating, and taking preventative measures, such as medications prior to leaving for your vacation, can all help protect you and your holiday.” Contracting travellers’ diarrhea caused by ETEC infection while on vacation can have a considerable personal and financial impact. Of those affected by the illness, up to one in five are bed-ridden for an entire day, and symptoms can last up to seven days. Despite the impact an 24

infection can have, the survey revealed that Canadians rank researching over-the-counter medications “just in case” as a higher priority than talking to a healthcare professional about preventative measures – such as travel vaccinations. “Many patients consider purchasing over-the-counter medications to manage travellers’ diarrhea in case it happens when travelling abroad, yet they don’t always think about protecting themselves before they leave for vacation,” saidTommy Cheung, pharmacist at Enhanced Care Medical Clinic, a multidisciplinary clinic based in Toronto.

Therapy Now Available For Stroke and Spinal Cord Injury Patients As MyndTec Launches MyndMove™ MyndTec, an award-winning, Canadian medical technology company announced the launch of its first commercial product, a revolutionary, new therapy for the treatment of arm and hand paralysis caused by stroke or spinal cord injury. MyndMove™ therapy is based on advanced non-invasive functional electrical stimulation and uses electrical stimulation to create new neural pathways for the recovery of voluntary function following injury to the brain or spinal cord. MyndTec has unveiled MyndMove at two rehabilitation conferences in Toronto, the National Spinal Cord Injury Conference and the American Congress of Rehabilitation Medicine. “This is truly a landmark moment in the evolution of FES therapy,” said MyndTec Founder Dr. Milos R. Popovic. “Multiple clinical studies have demonstrated the safety and efficacy of FES therapy for the treatment of paralysis and we can now offer this life-changing therapy to patients that might benefit”. “What makes MyndMove therapy so exciting is that the recovery of arm and hand function means that patients become more independent in performing routine activities of daily living such as eating, grooming, dressing and bathing,” said Diana Pliura, CEO of MyndTec. “With increased independence, patients gain dignity and the burden on families and our healthcare system is decreased.”

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

Helps to REDUCE the RISK of Antibiotic-Associated Diarrhea

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

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

Bio-K+ 50 Billion CFU Probiotic Capsule ®

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

Pharmacology

Hospital Protocol Administration

Potential Mechanisms of Action It was shown that L. acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2® strains have an excellent gastrointestinal survival rate. In fact, starter cultures resist to a pH of 2.5 and, when the strains are encapsulated with enteric coating, they can resist a pH of 1.5 for 2 hours1. Both strains survived to a high concentration of bile salt. This resistance allows a safe delivery of the probiotics to the GI tract and results in a production of antimicrobial molecules such as organic acids or bacteriocins. These molecules have been shown to directly eliminate various pathogenic bacteria such as C. difficile, E. faecium, E. faecalis, E. coli O157:H7, L. monocytogenes and methicillin-resistant S. aureus (MRSA)2,3. The secretion of an unknown metabolite was shown to reduce the cytotoxicity of toxin A/B secreted by C. difficile. Finally, administration of the CL1285® starter culture modulates the fecal microbiota by increasing the total lactic acid bacteria and total anaerobe count and reducing the Staphylococcus sp. Count4.

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

Health Claim5 • Helps to reduce the risk of Clostridium diffcile associated diarrhea (CDAD) in hospitalized patients. • Helps to reduce the risk of Antibiotic Associated Diarrhea (AAD). • Probiotic that forms part of a natural healthy gut flora. • Provides live microorganisms that form part of a natural healthy gut flora. • Probiotic that contributes to a natural healthy gut flora. • Probiotic to benefit health and/or confer a health benefit. • Provides live microorganisms to benefit health and/or to confer a health benefit.

Supplied Bio-K+® guaranties a minimum of 50×109 L. acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2® per capsule at expiration date. These bacteria are live and protected with an enteric coating. Lyophilized bacteria are the result of fermentation, concentration and freeze-dry processes. A mixture containing a predetermined concentration of lyophilized bacteria, cellulose, ascorbic acid, and magnesium stearate is prepared. This mixture is then added in a vegetable cellulose capsule pigmented with colloidal silicone dioxide. Then, the capsule is enteric coated. Each capsule contains: ≥50×109 live strains of L. acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2®. Non medicinal ingredients: ascorbic acid, cellulose, ethylcellulose, hypromellose, magnesium stearate, medium chain triglycerides, silicone dioxide, sodium alginate and titanium dioxide. Packaging options are: • 15 capsules: one bottle contains 15 capsules • 100 capsules: one box includes 10 sheets of 10 blister packed capsules • 250 capsules: one bottle contains 250 capsules • 1,000 capsules: one shipper includes 10 boxes of 10 sheets of 10 blister packed capsules Refrigerate at 4°C for maximum activity.

• Ensure the emptying of the stomach, eliminate gas (air and gastric secretions). • Before an intestinal surgery. • Liquid administration. • Allows stomach washing. • Allows to feed the patient on a short time period (force-feeding administration). • Analysis of gastric liquid. Millette et al.1 demonstrated that the Bio-K+® enteric coated capsules confer an excellent gastrointestinal (GI) survival to the probiotic strains. Millette et al.4 demonstrated the GI survival of the same strains under a pH ≥ 2.5 (without an enteric coating). It is not recommended to open the capsules, to rehydrate the lyophilized bacteria in a liquid and to consume the obtained suspension. The lyophilized bacteria are more sensitive to the acidity. If there are no other options available (i.e. patients with NGT receiving intravenous antibiotics), follow these steps to optimize the effectiveness of the Bio-K+® formula and to assure the safety of the patients: 1. Do not open the Bio-K+® capsules in the patient’s room. 2. Open and add the powder of one or two Bio-K+® capsules to 30mL of physiologic sterile water. 3. Stir the mixture with the tip of a 50 CC syringe. 4. With the 50 CC syringe, take the bacterial mixture. 5. Disinfect the external side of the syringe before bringing it in a patient’s environment. 6. Inject the suspension in the NGT, 15 minutes after the administration of a meal if possible. 7. Rinse the force-feed tube with 30 mL of physiologic water.

industry news Health Canada approves Yervoy® (ipilimumab) for firstline treatment of adults with metastatic melanoma Bristol-Myers Squibb Canada is pleased to announce that Health Canada has approved Yervoy® (ipilimumab) as a first-line therapy in adults with unresectable or metastatic melanoma, the most deadly form of skin cancer. This means that Canadians with newly diagnosed advanced melanoma, regardless of the subtype, will be eligible to receive the novel immunotherapy as their initial treatment. When Yervoy was first approved by Health Canada in 2012, for the treatment of patients who had failed or did not tolerate other systemic therapy for advanced disease, it was the first and only treatment for advanced melanoma proven to extend survival in a phase 3 trial. "Yervoy was the first immunotherapy treatment for metastatic melanoma introduced in Canada and it has transformed the way this deadly disease is currently managed. After decades with no new options, physicians suddenly not only had options but we were seeing long-term survival in some pretreated patients who were given Yervoy," said Dr.Michael Smylie, an oncologist specializing in melanoma at the Cross Cancer Institute in Edmonton. "Having Yervoy available now as an initial treatment will allow us to offer this potential benefit earlier in the disease course. This is good news for treating physicians and excellent news for our newly diagnosed patients." Unlike traditional therapies that target the tumour directly, immuno-oncology is an innovative field of cancer research and treatment focused on harnessing the power of the body's immune system to fight cancer. Such treatments target the very same pathways tumour cells use to evade recognition and destruction. Yervoy specifically blocks cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), which plays a role in suppressing the normal immune response. Yervoy blocks that suppression to allow the immune system to respond to melanoma cancer cells. "Nine years

ago my doctor put me on Yervoy which was experimental at the time. Having already been through a number of unsuccessful treatments, I did not expect to celebrate another birthday, Christmas or even experience another summer. This treatment didn't just save my life, it gave me my life back," said Kathy Barnard, founder of the Save Your Skin Foundation, a group dedicated to raising awareness about skin cancer, providing information about treatment options and funding research. "It's hard enough to be diagnosed with advanced melanoma and patients should have every possible chance on their side. I'm so pleased for what this approval means for newly diagnosed patients. This just gives more hope to patients in a disease area that only a decade ago had no hope at all." Over 30,000 melanoma patients have been treated with Yervoy. Yervoy has been recognized for its innovation by being awarded the Prix Galien Canada 2013 Innovative Product Award and earlier this year was named as one of Canada's top 10 new and emerging health technologies by the Canadian Network for Environmental Scanning in Health in its first "New and Emerging Health Technology Watch List."

Large Prospective Randomized Trial Confirms Benefit of EmbryoScope® Time-Lapse System A study accepted for publication in the renowned scientific journal Fertility & Sterility, confirms that a revolutionary and clinically certified technology can substantially increase the success rate in assisted reproduction. The use of the EmbryoScope® time-lapse system significantly increased ongoing pregnancy rates, implantation rates as well as significantly reduced early pregnancy loss. These are results from one of the world’s largest multi-center fertility clinics, IVI, based in Valencia Spain. The current study was conducted as a follow-up to a large retrospective analysis, which reported in 2012 that the combination of undisturbed culture and a customized embryo classification algorithm gave higher pregnancy rates. The data presented now confirm a relative improvement of more than 20 percent in clinical pregnancy rates by using the EmbryoScope® time-lapse system compared to standard evaluation procedures. In the current study, 843 patients were randomized between treatment in the EmbryoScope® time-lapse system and standard incubation. Embryo evaluation in the time-lapse system made use of a customized morphokinetic model applying morphology and time-lapse variables to select embryos, whereas standard morphology was used in the standard incubation system. Patients receiving EmbryoScope® treatment using a morphokinetic model were 23.2% more likely to have an ongoing pregnancy as well as 35.7% less likely to experience an early pregnancy loss. Dr.Marcos Meseguer and his team have made this algorithm, which is available in IVI laboratories. “This is the largest trial to date to study the clinical benefits of time-lapse technology on clinical outcomes, and we are delighted to confirm our previous findings,” says Dr. Meseguer, who conducted the survey. “IVI has always been at the forefront of offering our patients new and better treatments, and we were one of the first clinics in the world to offer the EmbryoScope® time-lapse system routinely to our patients. This also confirms that the research we have conducted in developing a customized embryo evaluation model will improve our efforts to help childless couples achieve the dream of parenthood.” The results reflect the benefit of using a customized evaluation model, which was developed by analyzing outcome results from previous treatments and combining this with the superior incubation in the EmbryoScope® time-lapse system. A previous study conducted by IVI indicates that improved incubation alone could not account for the large improvement in clinical outcomes observed in this study. “Unisense FertiliTech recognized the need to create advanced software to allow clinics to design and use models customized to their own clinical practice,” says CSO Niels Birger Ramsing. “We continue to invest resources to improve these software tools and to develop start-up embryo evaluation models which can be readily used by a wider range of clinics.” December 2014 | www.ihpmagazine.com

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industry news Health Canada Approves additional Claim for GENESTRA BRANDS™ GENESTRA BRANDS™ a trusted Seroyal® brand and a leader in probiotic research offering safe, effective, and reliable natural health products backed by clinical and traditional evidence, is proud to announce that Health Canada has approved an additional claim related to its proprietary Human Micro Flora (HMF) probiotic, HMF IBS Relief™. HMF IBS Relief™ offers rapid relief of symptoms associated with irritable bowel syndrome (IBS), prompting Health Canada to approve the following additional claim: “Adults and children over 11 years only: Helps improve symptoms of irritable bowel syndrome (IBS) such as bloating, satisfaction with bowel habits, and days with pain within 6 weeks.” “Genestra is pleased to receive an additional claim that supports the prompt symptom relief and effectiveness of HMF IBS Relief™,” said Yves Yau, President at Seroyal®. “This claim supports our ongoing commitment to develop effective research-based nutritional supplements.” Under the direction of Dr. Nigel Plummer, PhD., Genestra Brands® HMF strains were meticulously selected and diligently tested in double-blind, placebo controlled clinical trials. The double-blind, placebo controlled Sheffield IBS Trial tested four strains of high potency Human Micro Flora probiotics and concluded that Genestra’s proprietary HMF blend indeed proved effective, decreasing the severity of IBS symptoms and number of days with pain, while improving satisfaction with bowel habits and overall quality of life. The trial was published in the peer-reviewed journal Alimentary Pharmacology & Therapeutics. “Genestra’s human-derived probiotic strains more easily survive the rigours of the intestinal environment and are more efficient at colonizing the intestinal lining - ultimately yielding greater benefits,” said Dr. Plummer.

Prenatal maternal stress exposure to natural disasters predicts epigenetic profile of offspring The number of days an expectant mother was deprived of electricity during Quebec’s Ice Storm (1998) predicts the epigenetic profile of her child, a new study finds. Scientists from the Douglas Mental Health University Institute and McGill University have detected a distinctive ‘signature’ in the DNA of children born in the aftermath of the massive Quebec ice storm. Five months after the event, researchers recruited women who had been pregnant during the disaster and assessed their degrees of hardship and distress in a study called Project Ice Storm. Thirteen years later, the researchers found that DNA within the T cells - a type of immune system cell - of 36 children showed distinctive patterns in DNA methylation. The researchers concluded for the first time that maternal hardship, predicted the degree of methylation of DNA in the T cells. The “epigenetic” signature plays a role in the way the genes express themselves. This study is also the first to show that it is the objective stress exposure (such as days without electricity) and not the degree of emotional distress in pregnant women that causes long lasting changes in the epigenome of their babies. The health impacts on these children is less clear, but changes in the family of genes related to immunity and sugar metabolism detected in these babies, now teenagers, may put them at a greater risk to develop asthma, diabetes or obesity. Among the team of scientists who conducted this study are Lei Cao-Lei, Psychological Research Division, Douglas Institute Research Center and Department of Psychiatry, McGill University, Moshe Szyf, Department of Pharmacology and Therapeutics, Sackler Program for Epigenetics and Developmental Psychobiology, McGill University, and Suzanne King, Psychological Research Division, Douglas Institute Research Center and Department of Psychiatry, McGill University. Results of this study have been published in the international online publication PLOS ONE on September 19th, 2014.

First entirely fee-free medical marijuana clinic in South Western Ontario Canadian Cannabis Clinics (CCC), a new medical clinic focusing on medical marijuana as a treatment option, opened in St. Catharines and was be the first of its kind to operate with zero patient fees. With the recent implementation of the Marihuana for Medical Purposes Regulations (MMPR), medical marijuana has become a legitimate treatment option for many Canadians. However, most doctors with expertise in this field charge up to $400 annually for a prescription or other mandatory services. “Medical marijuana has the potential to improve the lives of so many Canadians,” said Joseph del Moral, Director of Canadian Cannabis Clinics. “But the costs being imposed by clinics specializing in this field are putting it out of reach for many. With the opening of this clinic, and future locations, we will be making medical marijuana more accessible to those patients considering it as a treatment option.” Canadian Cannabis Clinics has also partnered with Canada’s leading medical marijuana resource and counselling service, CanvasRx, to educate and inform patients about medical cannabis options. Selecting strains best suited for a patient’s needs, and completing the paperwork necessary to register with one of Canada’s licensed medical marijuana producers can be complex, so CanvasRx provides free, in-person consultations, and an easy-touse website (www.canvasrx.com), to help patients through all stages of the process. St. Catharines was selected as the site for CCC’s first location because it is a hub for the Niagara region. CCC has plans to open 10 more clinics across Canada in the next 12 months. “Our mission at Canadian Cannabis Clinics is to help Canadians get the best medical care available,” says Dr. Barry Waisglass, the first practicing doctor at CCC’s St. Catharines location, “and by removing the costs associated with accessing medical cannabis, and providing the counselling services through CanvasRx, we believe we can deliver on that promise.”

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calendar JANUARY January 8 CPR Healthcare Provider Level C Organized by: CCNM Toronto, ON For more information, visit http://www.ccnm.edu/ce_courses January 21 Biotherapeutic Drainage and UNDA Numbered Compounds Organized by: Seroyal Online Teleconference For more information, visit http://www.seroyal.com January 23-25 Healthy Breast Practitioner’s Program Organized by: CCNM Toronto, ON For more information, visit http://www.ccnm.edu/ce_courses January 28 Systemic Enzyme Therapy: Applying Clinical Trials to Clinical Practice Organized by: Seroyal Online Teleconference For more information, visit http://www.seroyal.com

For more information, visit http://www.mceconferences.com/medical-conferences.php February 17-20 Bowen Technique, Modules 1-4 Organized by: CCNM Toronto, ON For more information, visit http://www.ccnm.edu/ce_courses February 18 Biotherapeutic Drainage and UNDA Numbered Compounds Organized by: Seroyal Online Teleconference For more information, visit http://www.seroyal.com February 21 Optimizing Fracture Prevention in Primary Care Organized by: CFPC Toronto, ON For more information, visit http://www.cfpc.ca/UpcomingEvents/

FEBRUARY

February 21-22 Bowen Technique Modules 5-6 Organized by: CCNM Toronto, ON For more information, visit http://www.ccnm.edu/ce_courses

February 4 Biotherapeutic Drainage and UNDA Numbered Compounds Organized by: Seroyal Online Teleconference For more information, visit http://www.seroyal.com

February 25 Phytoembryotherapy: A Simple, Efficient & Highly Effective Adjunctive Therapy Organized by: Seroyal Online Teleconference For more information, visit http://www.seroyal.com

February 12 Clinical Applications for Pre and Post Childhood Vaccinations & Adult Influenza Organized by: Seroyal Online Teleconference For more information, visit http://www.seroyal.com

February 28 Individualized Nutrition for Women’s Health: Beyond Bio-Identical Hormones Organized by: Seroyal Toronto, ON For more information, visit http://www.seroyal.com

February 13-15 Infectious Diseases for Primary Care Organized by: MCE Conferences Steamboat, Colorado

MARCH

Organized by: Seroyal Online Teleconference For more information, visit http://www.seroyal.com March 5 Human Microbiome: A Key Driver in Lifelong Health and Disease Organized by: Seroyal Online Teleconference For more information, visit http://www.seroyal.com March 14 Opioid Dependence Treatment Core Course - Workshop Organized by: CFPC Toronto, ON For more information, visit http://www.cfpc.ca/UpcomingEvents/ March 21 Human Microbiome: A Key Driver in Lifelong Health and Disease Organized by: Seroyal Toronto, ON For more information, visit http://www.seroyal.com March 21-22 Naturopathic Doula Training Course Organized by: CCNM Toronto, ON For more information, visit http://www.ccnm.edu/ce_courses March 27-29 Facial Rejuvenation Acupuncture Certification Organized by: CCNM Toronto, ON For more information, visit http://www.ccnm.edu/ce_courses March 29 Motivation Interviewing & Coaching for Health Behavioural Change Organized by: CCNM Toronto, ON For more information, visit http://www. ccnm.edu/ce_courses

March 4 Biotherapeutic Drainage and UNDA Numbered Compounds December 2014 | www.ihpmagazine.com

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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)).

Quality Assurance

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

Test

Specifications

USP USP USP USP USP

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

USEPA USEPA USEPA USEPA

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

USP USP

Absent Conforms to limits

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

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

product profiles

Legend

g al ine ine thy lth re er tes try ics ics on lth lth tic llin a c c ea ssu anc abe chia iatr riatr triti Hea Hea se ceu edi edi eop u C Di sy d e n r H Pre u a l ra n M l M om Pe G ts N une en’s o P t d u a C u H or m om sc loo et al/N Asia anic p a i m B S V I D W t . n Bo tio Trad tri Nu

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

HMF Intensive Powder and HMF Intensive Capsules HMF Intensive Powder and HMF Intensive Capsules are clinically proven to supplement the normal intestinal microbiota and to help improve symptoms of irritable bowel syndrome. Both formulations include 25 billion CFU of proprietary humansourced probiotics that have a strong epithelial adherence and a naturally high tolerance to stomach acid. Free of wheat, gluten and soy. Ideal for vegans.

The First Whey-Based All in One! Introducing Progressive® WheyEssential! Each scoop provides 24g of New Zealand whey protein, 3g of fibre, 6-8 servings of fresh fruit, over 100% RDA of 13 vitamins and minerals, and more!

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Legend

product profiles

St Francis Herb Farm Canadian Bitters™ St Francis Herb Farm’s Canadian Bitters is an exceptional natural formula consisting of eleven herbs carefully chosen to revitalize digestive functions and enhance secretions of the liver, pancreas, stomach, and small intestine. Canadian Bitters can revitalize a broad range of digestive functions and is a valuable aid in maintaining good health.

NAC SAP from NFH NAC SAP from NFH provides 500mg per capsule of this important glutathione precursor. N-Acetylcysteine (NAC) is a precursor to glutathione synthesis and also acts on its own to reduce the effects of reactive oxygen species. NAC has been demonstrated to have antifibrotic activity and may be a useful treatment in disease processes that involve fibrosis. NAC also has mycolytic properties and decreases viscosity of lung secretions.

NEURAPAS® balance – To promote a healthy and balanced mood. 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. www.pascoe.ca

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product profiles

Legend

Curcummatrix

Super EFA Capsules and Super EFA Liquid Super EFA Capsules and Super EFA Liquid help to reduce serum triglycerides in adults, and support cognitive health and brain function in children and adolescents. Both products contain a concentrated dose of essential fatty acids (EFA) from fish oil; Super EFA Capsules contain 187.5 mg of DHA and 262 mg of EPA per capsule, and Super EFA Liquid contains 725 mg of DHA and 950 mg of EPA per teaspoon dose.

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.

L-Glutamine SAP L-Glutamine SAP provides the amino acid L-glutamine is an easy to dose palatable powder form at 5g per scoop. l-Glutamine is the most abundant amino acid in the human body .LGlutamine is metabolized in the small intestine and serves as an important fuel source for intestinal mucosa. Glutamine plays an important protective role in the intestinal tract, and is crucial for patients with increased permeability of the intestinal system, which can be seen in patients with inflammatory bowel diseases including for example Crohn’s disease or ulcerative colitis, as well as in irritable bowel syndrome and allergies. This amino acid plays an important role in nutrient metabolism, the immune system, protein turnover and acid-base balance.

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Legend

product profiles

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

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

PaleoComplete-DF PaleoComplete-DF provides the nutrients needed to fuel busy healthy lives. In compliance with the Paleolithic Diet, this PaleoComplete-DF soy-free, dairyfree and grain-free blend is ideal for low-carbohydrate diets as either a meal replacement or supplement. This formula is naturally sweetened with Stevia and has a delicious berry or vanilla flavour that will not affect insulin levels and will support healthy weight loss and muscle growth—an ideal choice for a detoxification program. PaleoComplete-DF provides optimal ratios of macronutrients, vitamins and minerals to sustain energy levels for all of life’s activities with hypoallergenic Pea Protein isolate providing 17g of protein per serving. Added to this blend are NatureFolate, a bioavailable, active form of folate; Magnesium Creatine chelate to support muscle mass and endurance; liver support via phosphatidylcholine; and prebiotic inulin fibre for optimal gut and metabolic health. PaleoComplete-DF is part of a complete management plan for cholesterol and blood sugar control, yeast overgrowth, and heavy metal toxicity.

December 2014 | www.ihpmagazine.com

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Nutritional Fundamentals for Health Inc.

Focus on Cancer Coriolus Versicolor SAP contains PSK and PSP, which both showed favourable results against gastric/colorectal, lung, and breast cancers. Coriolus has also increased NK cell activity and immune activation on patients with chronic fatigue syndrome. Please see product monograph on opposite page. EGCG SAP - Consuming green tea has been associated with lowered risk of several types of human cancers and cardiovascular disease. The major chemopreventive agent of green tea is epigallocatechin gallate (EGCG), a potent natural antioxidant. Grape Seed SAP contains proanthocyanidins, which have a wide spectrum of pharmacological, therapeutic, and chemoprotective properties. It has also been found to be cytotoxic toward human breast, lung, and gastric adenocarcinoma cells. Reishi SAP is particularly known for its immune-modulating effects, which have been demonstrated by an increase in T lymphocytes. Shiitake SAP can be used to help support healthy immune function and cardiovascular health, as well as a source of antioxidants. It can also help support the immune system, as well as improve quality of life for patients undergoing chemotherapy. 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 Please visit our website nfh.ca to view our full line of products

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Our products are proudly Canadian (created and produced in Canada)

2014-12-09 3:43:05 PM

Coriolus Versicolor SAP PRODUCT MONOGRAPH

Coriolus versicolor is a medicinal mushroom that has been heavily studied in a variety of different types of cancers.[1] Polysaccharide K (PSK) and polysaccharide peptide (PSP) are both complexes consisting predominantly of polysaccharides and proteins which are soluble in water but not in ethanol, therefore ensuring the proper extraction method used is very important.[1] PSK has been shown to boost immune cell production, improve side effects from chemotherapy and radiotherapy, and enhance tumor infiltration by dendritic and cytotoxic cells to extend survival in cancers of the stomach, colon, uterus, and lung in combination with conventional treatment.[1] PSK has also demonstrated the ability to enhance the activity of both glutathione peroxidase and superoxide dismutase.[1] PSP helps enhance immune status in patients with cancer of the lung, cervix, ovary, stomach, or esophagus.[1]

CORIOLUS AND CANCERS

PSP from Coriolus versicolor has demonstrated both antitumor and immunomodulating effects when used as an adjuvant to chemotherapy.[2] Researchers in this study where hoping to determine the mechanism by which PSP has its effect.[2] A comparison was made between PSP treatments with and without prior incubation in phytohaemagglutinin (PHA; a process often used in experimentation with the immune population).[2] Using flow cytometry without PHA treatment, researchers determined the proliferative capacity of PSP on a variety of different immune populations in peripheral blood mononuclear cells.[2] PSP was found to significantly increase the number of monocytes (CD14+/CD16-) where proliferations of T cells, NK, and B cells did not experience significant changes.[2] The ability to stimulate monocyte and macrophage function with PSP may be an effective intervention in targeting tumors.[2] One of the leading causes of cancer deaths is nonsmall cell lung cancer (NSCLC), and over 60% of patients present in advanced stages.[3] Researchers completed a 28-day double-blind, placebocontrolled, randomized trial to evaluate the effect of PSP on patients with NSCLC who had completed conventional treatment.[3] Thirtyfour patients with NSCLC where randomized into either treatment with PSP or control for 28 days.[3] At the end of the trial, patients in the treatment group had significant improvements in blood leukocyte and neutrophil counts, serum IgG and IgM, as well as percentage body fat, which were not seen in the control group.[3] There was no improvement seen in the NSCLC-related symptoms in the treatment group; however, there were significantly less patients that had to withdraw because of disease progression compared to the control group 5.9% versus 23.5%, respectively.[3] There were no adverse reactions reported attributed to the trial medications.[3] The authors concluded that PSP treatment appears to be associated with a slower deterioration in patients with advanced NSCLC.[3] Researchers looked at patients with stage-III uterine and cervical cancers in combination with radiotherapy, which where given PSK (3-6 g/d).[1] Patients demonstrated enhanced survival and increased sensitivity of the cancers to radiotherapy.[1] In another trial with cervical cancer patients, all patients received the same dose of radiotherapy, with the treatment group also receiving PSK. The treatment group demonstrated an increase in clearance of cancer cells of 36% versus 11% in controls.[1] In another study using the Coriolus biomass at 3 g/d, researchers looked at the regression rate in LSIL lesions and found the treatment groups regression was 72.5% compared to 47.5% in controls. It also increased the clearance of high-risk HPV strains from 8.5% in controls to 91.5% in the treatment group.[1] In a systematic review and meta-analysis from randomized, placebocontrolled, double-blind trials, researchers wanted to assess the

For more information visit www.nfh.ca

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efficacy of Coriolus for survival in cancer patients.[4] Thirteen clinical trials where included in the analysis.[4] Findings demonstrated that Coriolus versicolor use results in a significant survival advantage compared with standard conventional treatment on its own.[4] Patients who received Coriolus showed a 9% absolute reduction in 5-year mortality, resulting in one additional patient alive for every 11 patients treated.[4] Patients with breast, colorectal, or gastric cancer who had been treated with chemotherapy showed the best results in combination with Coriolus in terms of 5-year survival rates.[4]

CORIOLUS AND HERPES

Herpes simplex virus (HSV) causes herpes genitalis and recurrent herpes labialis.[5] Researchers wanted to explore the mechanisms by which PSK exerts a protective effect against HSV infection.[5] HSV-1 GC+ was inactivated by PSK in a dose-dependent manner of concentrations of PSK and virus titers.[5] PSK at concentrations as low as 0.31 mg/ml was shown to inactivate the infectivity of HSV-1 GC+ (labcultured strain). Inactivation required at least 30 min of incubation at 37 C, with maximal inactivation observed at 60 min incubation time. Clinically isolated strains of HSV-2 were also inactivated by PSK, but clinically isolated strains of HSV-1 were resistant to PSK.[5] HSV treated with PSK maintained its ability to absorb the cell membrane, but did not synthesize viral proteins.[5] The data suggests there is a biological difference between HSV-1 and HSV-2, and also suggests that PSK may be able to inactivate HSV in lesions at peripheral sites of recurrent herpes.[5]

CORIOLUS AND MICROBIOME

Microbial flora in the intestines of humans plays a critical role in the maintenance of intestinal health as well as in the pathophysiology of several disorders, including inflammatory bowel disease, clostridium difficile infections, and antibiotic-associated diarrhea.[6] Prebiotics can confer a health benefit by beneficial effects on the intestinal microbiome, whereas antibiotics can disrupt the microbiome, leading to side effects.[6] Researchers compared the effects of the prebiotic PSP from Trametes versicolor (another name for Coriolus versicolor) to those of the antibiotic amoxicillin on the human gut microbiome.[6] Twenty-four healthy volunteers were randomized into three groups: PSP, amoxicillin, or control.[6] Stool specimens were analyzed over eight eeks. The PSP group showed clear and consistent microbiome changes, consistent with its activity as a prebiotic, and strong microbiome clustering was noted where the baseline microbiomes tended to remain stable.[6] Amoxicillin treatment caused a significant change in the microbiome, with the most notable change being an increase in Escherichia/Shigella, which persisted to the end of the study (42 days after antibiotic therapy stopped). Researchers concluded that microbiomes of healthy individuals show substantial diversity, but remain stable over time. They also noted that amoxicillin alters the microbiome and recovery from this disruption can take several weeks, but that PSP acts as a prebiotic to modulate human intestinal microbiome composition.[6] References

1. Powell, M. Medicinal mushrooms: a clinical guide. East Sussex: Mycology Press, 2.[0][10] 2. Sekhon, B.K., et al. “PSP activates monocytes in resting human peripheral blood mononuclear cells: immunomodulatory implications for cancer treatment”. Food Chemistry Vol. 138, No. 4 (2013): 2201– 2.[2][09] 3. Tsang, K.W., et al. “Coriolus versicolor polysaccharide peptide slows progression of advanced non-small cell lung cancer”. Respiratory Medicine Vol. 97, No. 6 (2003): 618–.[6][24] 4. Eliza, W.L., C.K. Fai, and L.P. Chung. “Efficacy of Yun Zhi (Coriolus versicolor) on survival in cancer patients: systematic review and meta-analysis”. Recent Patents on Inflammation & Allergy Drug Discovery Vol. 6, No. 1 (2012): 78–.[87] 5. Monma, Y., T. Kawana, and F. Shimizu. “In vitro inactivation of herpes simplex virus by a biological response modifier, PSK”. Antiviral Research Vol. 35, No. 3 (1997): 131–.[1][38] 6. Pallav, K., et al. “Effects of polysaccharopeptide from Trametes Versicolor and amoxicillin on the gut microbiome of healthy volunteers: A randomized clinical trial”. Gut Microbes Vol. 5, No. 4 (2014) [Epub ahead of print]

2014-12-09 3:43:06 PM

cover story

PROJECT SOIL Food Production at Health Care Institutions By Philip Rouchotas, MSc, ND Photography By Christine Kufske

www.ihpmagazine.com | December 2014

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Phil Mount and Jenny Weickert (Farm Project Manager)

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cover story

he “local food” phenomena… A truly incredible happening… Resurgence of farmers markets in communities across the country, individual citizens and families committing to generate at least a portion of their own food consumption in their own backyards or condo patios, growing systems emerging that allow the hobby gardener to produce food through vertical systems that occupy windows in peoples homes, and the nation- wide phenomena of people secretly raising chickens in their backyards – secretly because most municipalities have by-laws banning the practice. So what about getting institutions involved? What about getting hospitals to grow the food they serve in their cafeterias? Universities to grow the food served in on- campus restaurants? How about inpatient care centres growing food for the centre, and having patients participate in the growing, harvesting, and processing? Phil Mount, PhD, is the principal researcher of an OMAFRAfunded study investigating this very principle. Project SOIL (Shared Opportunities on Institutional Lands) has a mandate to assess the feasibility of institutions generating their own supply of food. It began with previous projects that assessed obstacles

to local food supply in Ontario. The Toronto Food Terminal is the main point of control for all food, local and imported, in Ontario. This is convenient to all levels of the food supply chain—from producers to distributors to retailers, and of course consumers— but not the most effective or efficient way to deliver local food to local regions. A need was identified for a means to deliver locally-produced food to “large” consumers – including healthcare facilities— while keeping costs down, and returning a fair price to the farmers. That research also concluded that one of the challenges to increased local food production is the lack of access to land for new and young farmers. Another research project identified cost as one of the main barriers to increasing local food in health care institutions. But at the same time, it was clear that many of these institutions were rich in another resource: land. The OMAFRA funding, under the “New Directions” research program, challenged Dr Mount and colleagues to ask the question “how could we bring these resources together to encourage hospitals and other institutions to grow their own local food”? The research has focused on healthcare and educational facilities, yet their work can be easily applied across a

RESOURCES FOR THE URBAN- FARM ENTHUSIAST ❯ The Market Gardener – a successful grower’s handbook for small- scale organic farming, by Jean- Martin Fortier ❯ Four- Season Harvest – organic vegetables from your home garden all year long, second edition, by Eliot Coleman ❯ TEDx Warwick – Charlie Price - Aquaponics

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cover story

broad range of institutions, from seniors’ residences to daycares. Virtually any facility with land is indeed an ideal candidate. Project SOIL is actively working with five pilot sites. A major focus of the project is to demonstrate the benefits that derive from on-site food production at any scale. While the positive influence of smaller growing projects is immense, one important goal is to be able to demonstrate the feasibility of large-scale food production initiatives using lands of healthcare and other institutions. But this does not mean production is limited to facilities with large tracts of land: intensive food production practices can grow large quantities on very small plots! The five ongoing pilots of Project SOIL are as follows: • Homewood Health Centre – Guelph, Ontario. Homewood is a centre that treats addiction and mental health concerns. The facility has had a rich history of “therapeutic horticulture”, and are now using the newly-designed Victorian Gardens as a means of food generation, yet also as a tool to get patients moving, active, and participating in their own food production. • Food School Farm – Fergus, Ontario. In partnership with a community non-profit—the Wellington Centre for Sustainable Agriculture—the district high school uses a century farmhouse and a one- acre garden as an intensive organic farm. A full semester, all day, integrated sustainable agriculture program for grade 11 students is conducted in the farmhouse, and students participate in the planting, maintaining, harvesting, and processing of the organic produce. • KW Habilitation. A community organization founded by parents focused on helping individuals with developmental disabilities. The team created the “Our Farm project”, that includes gardens at an eight- acre rural site, as well as an urban site in downtown Waterloo maintained by a student group“Young City Growers”. • Lakehead Psychiatric – Thunder Bay, Ontario. Lakehead runs a series of social purpose training programs aimed at introducing outpatients to vocations they may pursue in the community. In the GreenWerks Gardens, clients learn

planting, growing and harvesting skills. The produce is either sold in an on- site café and market, used by the foodservice provider, or sold at a discount to the Regional Food Distribution Agency, who delivers to over 40 food relief sites in Northwestern Ontario. • Glengarry Memorial Hospital – Alexandria, Ontario. The Glengarry hospital started a therapeutic garden in 2012 as a way to get acute care and stroke rehabilitation patients up, moving, and engaged in an activity. The facility will be initiating its pilot in the spring of 2015, and will use the opportunity to start a Small Plot Intensive (SPIn) farming project. While a major goal of Project SOIL is to determine the feasibility of large- scale food production in public institutions, the benefits of gardening —well known to every garden enthusiast— go far beyond the simple calculation of kilos of produce harvested. The impacts of garden projects are far-reaching: it is difficult to describe the level of gratitude and satisfaction that derives from consuming a product you yourself grew. Gardens bring people and communities together, and impart a deep knowledge and respect for nature to every participant. The therapeutic impact of spending time in greenspace and working with plants —a topic recently reviewed in this journal—is supported by an impressive body of science. These intangibles are in no way lost to Dr. Mount and the Project SOIL team. They see first hand the value of each project going far beyond the produce harvested. It will invariably be difficult to quantify these aspects of each individual garden project they observe, yet rest assured the task has fallen into capable hands. Every member of the Project SOIL team shares one simple passion – a love of gardens! Dr Mount stressed the importance of “scale” and “value” in our interview, yet agrees defining value will be a challenge. Has a project failed if it produces 30% of the food needs of the facility in question, yet simultaneously acts as a place of healing for its residents? …or acts as a meeting place for large numbers of community members? The “local food phenomena”, and the growing tsunami that December 2014 | www.ihpmagazine.com

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cover story

is people’s interest in growing their own food, simply can not be stopped. Italian immigrants post World- War II are largely credited with turning every paved lot in Brooklyn, NY into tomato gardens (simultaneously dispelling the long- held myth by Americans that tomatoes were poisonous). Pre World War II, people grew vegetables in their front yards. Post world war II, it was considered a sign of affluence to grow flowers instead of vegetables, to the point where it is considered unattractive to grow food in front of your home. Yet one-by-one, front- yard vegetable gardens are making a comeback. A recent Globe and Mail article highlighted a major grocery store chain looking to convert the rooftops of all their stores into greenhouses, sighting that 50% of the cost of produce is transportation from farm to store. Toronto’s most affluent neighbourhoods house hardened criminals; families that spend thousands of dollars to build custom structures that house hens, so they can harvest a handful of fresh eggs each morning, all under extreme secrecy, in fear they will be found guilty of breaking local by-laws and their hens taken from them. At least Vancouver and a handful of other Canadian municipalities have entered the 21st century, allowing hens within the city core. My personal love of gardening and gardens attracted me to showcase Project SOIL, yet their work goes far beyond motivating the individual to grow some veggies in their yard. Most certainly the Project’s members share such a passion, yet their vision is far more ambitious. The environmental cost of current food distribution models is horrific. We are all aware of this, as it has been a major force driving the “local food phenomena”. We often discuss major environmental problems, yet most of us feel helpless to truly make an impact. We try on a personal level to do what we can; reduce/ reuse/ recycle, car pool, walk, grow a garden. The potential impact of Project SOIL is truly immense. Project SOIL is ambitiously attempting to bring radical change to the problem. By bringing together institutional leaders and those with the passion and skills to farm their land, truly large scale food production could happen on the tens of thousands of acres of land currently covered by lawn that surrounds virtually every public institution in the country. An environmental impact of unfathomable importance has the potential to be added to the impressive list of benefits we already assign to gardens. We at IHP wish Project SOIL much success.

THE PROJECT SOIL TEAM: WWW.PROJECTSOIL.CA ❯ Phil Mount, Principal Investigator Department of Geography and Environmental Studies, Wilfrid Laurier University ❯ Irena Knezevic, Co-investigator School of Journalism and Communication Carleton University ❯ Brendan Wylie-Toal, Collaborator My Sustainable Canada ❯ Linda Varangu, Collaborator Canadian Coalition for Green Health Care ❯ Louise Quenneville, Collaborator Hôpital Glengarry Memorial Hospital ❯ Doug Dowhos, Collaborator St Joseph's Care Group ❯ Chris Jess, Collaborator Centre Wellington District High School ❯ Jenny Weickert, Collaborator KW Habilitation ❯ Tamaura Proctor, Collaborator Homewood Health Centre ❯ Dr. Alison Blay Palmer, Advisor Department of Geography and Environmental Studies, Wilfrid Laurier University ❯ Dr. Karen Landman, Advisor Landscape Architecture, University of Guelph

December 2014 | www.ihpmagazine.com

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clinic profile

Marsden Centre of Naturopathic Excellence Leading Integrative Oncology By Christopher Habib, ND Photography By Anne DeHaas

ased on its success, it is hard to believe that The Marsden Center of Naturopathic Excellence (MCNE) has only been opened for 5 years. The clinic is managed by Dr. Eric Marsden, ND. During his education, Dr. Marsden had the opportunity to travel to Germany once to twice a year over a period of about 10 years. In this process, he witnessed first-hand integrative cancer care and he got really excited about applying it in Canada. He even remembers visiting hospital floors where there were high-end diagnostics on one end and then rooms for naturopathic treatments on the other. The atmosphere and the quality of care was inspiring. The lack of awareness of these integrated approaches in Canada was also a strong motivating factor for him. The clinic was created as a result of these experiences, as Dr. Marsden wanted to build a space capable of providing that high level of care. He also wanted to bring the some of the more advanced diagnostics to the naturopathic profession. He wanted to facilitate access to quality care patients and practitioners.

2338 Major Mackenzie Dr. W Maple ON, L6A 3Y7 Phone: 905-508-4498 info@mcne.ca www.mcne.ca

www.ihpmagazine.com | December 2014

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clinic profile

December 2014 | www.ihpmagazine.com

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clinic profile

Dr. Eric Marsden, BSc, ND – Clinic Director Dr. Von Chaleunsouk Marsden, BSc, ND – Assistant Director Dr. Rebecca Lee, Hon. BSc, ND Dr. Ashley Chauvin, BSc, RTT, ND Dr. Lei Gu, BSc, ND Martha Sharpe, ND – Resident Pamela Tarek, RHN Hilda White – Reception Barb Czapla – Reception The clinic is an impressive 6000 square feet in total and services up to 200 patient visits a week. There are 7 treatment rooms, a full laboratory, an infusion therapy suite (where 8 chairs are available for IV therapy), a hyperthermia treatment suite, a professional dispensary, a tea room and organic café, meeting and lecture space, and administrative offices. Dr. Marsden believes that the clinic’s advanced therapeutics make a major difference for patients. MCNE offers loco-regional hyperthermia (they are one of only 4 clinics in Canada that offer this). They also offer mistletoe therapy (Dr. Marsden actually brought Helixor to Canada). The clinic has patients that come from the United States who request it. In addition to these therapies, the clinic is always on the cusp of infusion therapy. The team at MCNE utilizes a thorough and unique set of diagnostics. They have unique German devices that allow for bio-electronic terrain assessment (this measures things like pH, redox potential, and resistivity). They also do microscopy, bio-impedance analysis, as well as basic tests like ECG and spirometry. There use two special labs from Germany, Maintrac and BioFocus. Maintrac provides a method of quantifying circulating tumour cells within a sample of blood. It can be used as a tool for prognosis and for preventive protocols. The doctors at MCNE see a direct clinical relation. BioFocus provides genetic characterization. They isolate the circulating tumour cells and do gene testing on them, which may help to identify if certain therapies may be particularly helpful. In terms of Canadian 46

providers, the team at MCNE uses CELLSEARCH®, a Health Canada approved diagnostic platform. In particular, they use it to see if a treatment is working. It may change prognosis, but is also useful for analyzing quality of life. The team at MCNE have a lot of combined experience and have treated rare cancers. All of their medical information is linked into their electronic medical records system. They use a company that allows them to do some data mining. The same system (Accuro®EMR) is used by many medical doctors. All patients are ICD-coded. Dr. Marsden hopes that they will be able to link into OLIS, the central lab system for Ontario. The eventual goal is that if there are prescription changes made for patients, all practitioners will be made aware of it. It will also allow for the centralization of patient data. MCNE is one of the few clinics where there is a standardized approach to cancer patients. They look at where patients are in the disease pathway and what that means in terms of the treatment goals. They analyze what this means in terms of the therapeutics that they can administer (especially if concunrently with conventional approaches). The result is that the clinic provides a better standard care for patients. They actually evaluate and quantify their treatments to clearly establish how effective they are, not only on the whole, but also for each individual patient. MCNE offers a residency program. It includes 2 residents on at one time and they stagger it so that each year they bring on a new practitioner. This allows for a mentorship component, so

www.ihpmagazine.com | December 2014

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clinic profile

that the senior resident can help with education and training of the junior resident. Many residents stay to practice as associates after their residency. Some practitioners on the team will specialize after (Dr. Lee for example has a strong emphasis in Traditional Chinese Medicine, so does all the acupuncture and related intakes). The residents do all the infusions and manage new patient assessments. The goals for the residents are to understand the foundations of cancer care and environmental medicine. In the second year of residency, the focus is on case management. All of the practitioners try to work together and usually there will be one practitioner who will lead a patient’s care based on their specialty training. For example, a team member may have a consult with the primary doctor’s patient directly or engage in collaborative case management with the primary doctor. The biggest challenge for MCNE is the integration of care. They have a difficult time implementing a collaborative and cooperative approach with others. “We try our best,” says Dr. Marsden. “Medical doctors, oncologists, and naturopathic doctors all want what’s best for their patients. One big concern from doctors and specialists is that they are worried about the cost of treatment for the patients.” The other perceived obstacle is regulation: it has the potential to allow for more integration, but also has the risk of being restrictive. To address the cost concerns, last year the MCNE performed $100,000 worth of subsidized treatments for patients. Remarkably, they are in the

process of trying to create a charity in which all naturopathic doctors could access funds for their patients to receive care. Dr. Marsden and his team always try to be on the cutting edge of oncology research. They also have a very strong environmental medicine program. They believe it plays a more serious role in both primary and secondary prevention with regards to oncology. When asked if he has any messages for other doctors, Dr. Marsden says: “Integrative approaches to oncology are incredibly important. Cancer is the leading cause of death in North America. We don’t have it right. Even the most emergent therapeutics are only adding months to life. The fact of the matter is that we continue to look at cancer as a battle. We look at the cancer as our enemy and the patient as our battleground. Cancer is a whole body disease and it involves the regulation of the immune system. Treating rationally and effectively, while using therapies where there is good clinical evidence is the best way to go.” Dr. Marsden encourages his patients to be strong advocates for themselves. In the near future, the hope is that the clinic will be involved in a multicenter trial for cancer care. The team at MCNE hopes to publish more papers and to continue presenting their findings at conferences. They want to open doors to collaborate with cancer treatment centers in Ontario. “Because the stakes are so high in oncology, the rewards can be wonderful,” Dr. Marsden says. We would like to thank the team at MCNE for sharing their story with IHP. December 2014 | www.ihpmagazine.com

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company profile

Designs N for Health An Exclusively Professional Line By Philip Rouchotas, MSc, ND

atural health products companies that exclusively service healthcare providers have become a rare phenomena. Designs for Health has entered the Canadian landscape after decades of success in the USA, and brings with them a keen eye for evidence- based formulations, a commitment to quality, and a model that services healthcare providers as its sole customers. Cofounders Linda Lizotte, RD, and Jonathan Lizotte, CEO initiated Designs for Health in 1989. Linda had established a successful chain of nutritional consultation centres whose principle focus was weight loss. She found it immensely difficult to find natural health products she felt confident administering to the clients of these multiple centres. Linda had also developed an education series principally for employees of the centres, yet found integrative healthcare professionals eager to attend as wellâ&#x20AC;Ś The culmination of frustration from dealing with then- available lines of natural health products, as well as the professionalâ&#x20AC;&#x2122;s encouragement and input into required formulations led to the launch of Designs for Health. Rapid growth ensued, and today Designs for Health is a manufacturer of over 300 natural health products, overseeing raw material procurement, testing, manufacture, retesting, packaging, and distribution.

www.ihpmagazine.com | December 2014

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company profile

The company’s focus on best available evidence was present from day one. In the early days, Robert Crayhon, established author of “The Carnitine Miracle” and “Nutrition Made Simple” joined the Designs for Health team. Robert Crayhon is largely credited for introducing integrative healthcare providers to therapeutic application of many of the “neuroprotective” nutraceuticals, notably acetyl-l-carnitine, phosphatidylserine, and phosphatidylcholine. Dr David Brady, ND, DC has since joined the Designs for Health team as their Chief Medical Officer for 11 years. Dr Brady serves as the Vice Provost for the Division of Health Sciences, Dean of the College of Naturopathic Medicine, and Director of the Human Nutrition Institute at the University of Bridgeport in Connecticut. Dr Brady highlighted for us many of the advancements within the natural health products industry that Designs for Health was among the first to introduce. “Designs for health was the first professional line to remove all synthetic folate from its formulations, and provide the MTHR form of the vitamin”. “Also, most concentrated fish oils claiming to be triglyceride form are truly 60% triglyceride with as much as 40% as ethyl ester… Designs for Health utilizes a process that allows high potency concentrates to deliver 95% of fatty acids as triglyceride”. Dr Brady goes on to describe “Designs for Health also pioneered the concept of bioidentical nutrients… focus on enhanced bioavailability… utilizing bisglycinate technology…” He got very excited describing Flavocoxid... “Flavocoxid is a specially manufactured and extensively studied botanical in the

medical food line. Although there are many natural agents with anti-inflammatory properties in naturopathic and integrative medicine, there are not many backed by the rigorous scientific studies as flavocoxid”. Dr Brady repeatedly stressed that a major focus of Designs for Health is education. Educational seminars ultimately led to the creation of the company, and a strong commitment to educating professionals remains a cornerstone of the Designs for Health model. I gratefully got to discuss a handful of clinical topics with Dr Brady and was quickly left with several topics I needed to go look into further. Rest assured I will be eager to attend a Designs for Health seminar when they come to town… I am excited to see Designs for Health arrive in Canada… The Natural Health Products Directorate seemed to scare many companies away from Canada when they came into being in 2004. However, those of us who have worked with the system acknowledge that while far from perfect, the system is more than capable of being worked with. It is refreshing to see a company that does not fear the modest scrutiny demanded by Health Canada. Furthermore, it is refreshing to see an established American company that recognizes the immense contribution of Canadian providers of integrative healthcare, and values that contribution enough to overcome the hurdles required to cross the border. Their commitment to quality, scientific scrutiny, and clinical efficacy are obvious and welcome. Equally important is their commitment to the health care provider as a professional brand. December 2014 | www.ihpmagazine.com

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The Journal Of

p57

Meditation

Impact on gene expression By Polina Kapoustina, ND (Cand)

p62

Lifestyle Genomics

The Next Step to Individualized Medicine

By Mansoor Mohammed, BSc (Hons Mol Gen), PhD, Robyn Murphy, ND, Emily Fitzgerald, ND, and Christopher Habib, ND

p69

Chemotherapy and Radiation- Induced Oral Mucositis

Integrative management By Meighan Valero, ND

p74

Mechanism of melatonin in oncology The great multi-tasker By Jessa Landmann, ND

www.ihpmagazine.com | December 2014

editor’s letter

Happy Holidays This is a very special time of year… A chance to reflect on the year that was, prepare for the year ahead… We at IHP are hopeful everyone is finding ways to spend time with friends and loved ones… Readers of IHP are no stranger to my personal love of gardening and concepts surrounding urban food production. I am very excited to present Project SOIL as the issues cover story… Principal Investigator Phil Mount, PhD, is attempting to evaluate the feasibility of using the vast lands surrounding public institutions as spaces to produce food! Feasibility goes far beyond yield of produce. Many inpatient facilities have found the practice provides an immeasurably valuable therapeutic outcome to participants… Equally important is the potential the project has to truly impact the environment, most notably with regards to the horrifying impact of current food transportation models. The issue’s clinic profile is long overdue. Eric Marsden, ND, has set the bar regarding the practice of integrative oncology for many years. We are excited to present his cutting edge facility and the dedicated team that makes the Marsden Centre of Naturopathic Excellence the world- class facility it is. The issue’s features include reviews covering the impact of meditation on gene expression, effective treatments for chemotherapy/ radiation- induced mucositis, and a look at the potential for a genetic screen offered by ND’s to impact clinical practice. The issue’s CE article focuses on mechanisms of action governing the role of melatonin in cancer care. Best Regards, Philip Rouchotas, MSc, ND Editor-in-Chief We invite questions or comments. philip@ihpmagazine.com

www.ihpmagazine.com | December 2014

Publisher | Sanjiv Jagota (416) 203-7900 ext 6125 Editor-in-Chief | Philip Rouchotas, MSc, ND (416) 203-7900 ext. 6109 Associate Editor | Christopher Habib, ND Art Director | Scott Jordan (416) 203-7900 ext. 6106 Production Manager | Erin Booth (416) 203-7900 ext. 6110 Junior Designer | Tamara Kelly Contributors Philip Rouchotas, MSc, ND Christopher Habib, ND Mansoor Mohammed, BSc (Hons Mol Gen), PhD Meighan Valero, ND Emily Fitzgerald, ND Robyn Murphy, ND Jessa Landmann, ND Polina Kapoustina, ND (Cand) President | Olivier Felicio (416) 203-7900 ext. 6107 Controller & Operations | Melanie Seth Advertising Information Sanjiv Jagota | Tel: (416) 203-7900 ext 6125 Email: sanjiv@ihpmagazine.com Circulation Rive Gauche Media 1235 Bay St., suite 400 Toronto, Ontario, M5R 3K4 Email: circulation@ihpmagazine.com

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peer review

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

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

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

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

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

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

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

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

Ashley Weber, HBSc, ND Upper Beach Health and Wellness 1937 Gerrard St E. Toronto, Ontario ashleywebernd@gmail.com Berchman Wong, ND Adjust Your Health 5809 Macleod Tr SW, Suite 218 Calgary, Alberta T2H 0J9 berchman.nd@gmail.com Betty Rozendaal, BES, MA, ND Thornhill Naturopathic Health Clinic 12A Centre Street Thornhill, Ontario L4J 1E9 drbetty@thornhillnaturopathic.ca Brock McGregor, ND McGregor Naturopathic 220 St Clair Street Chatham, Ontario N7L 3J7 drbrock@mcgregornd.com Carol Morley, ND Zawada Health 201 City Centre Drive, Suite 404 Mississauga, Ontario L5B 2G6 info@zawadahealth.com Christopher Knee, ND, MSc The Dempster Clinic â&#x20AC;&#x201C; Center for Integrated Medicine 97 Scollard Street Toronto, Ontario knee.christopher@gmail.com Claire Girgis, ND Zawada Health 201 City Centre Drive, Suite 404 Mississauga, Ontario L5B 2G6 claire@zawadahealth.com

David Miller, BSc, ND 662 Gustavus Street Port Elgin, Ontario N0H2C0 drdavend@yahoo.ca Denisa Maruyama, ND Kona Wellness Center for Integrative Medicine 74-5565 Luhia Street Suite C-2 Kailua-Kona, Hawaii drmaruyama@konawellness.com Elaine Lewis, HBSc, ND Back to Play Chiropractic 592 Rathburn Road West Mississauga, Ontario L5B 3A4 elewis@ccnm.edu Elena Rossi, MSc, ND Mahaya Health Services 105-2 College Street Toronto, Ontario M5G 1K3 info@mahayahealth.com Elizabeth Cherevaty, BSc, ND Norfolk Chiropractic Wellness Centre 86 Norfolk Street, Suite 101 Guelph, Ontario N1H 4J2 elizabeth.cherevaty@gmail.com Erin Balodis, BSc, MSc, ND Kingswood Chiropractic Health Centre 1210 Hammonds Plains Road Hammonds Plains, Nova Scotia B4B 1B4 erinbalodis@gmail.com

Isaac Eliaz, MD, MS, LAc Amitabha Medical Clinic & Healing Center 7064 Corline Ct #A Sebastopol, California 95472-4528 ieliaz@sonic.net Jacob Scheer, DC, ND, MHSc 2100 Finch Ave. W. #206 North York, Ontario M3N 2Z9 Jacob.Scheer@utoronto.ca Jiselle Griffith, BSc, ND The Health Hub Integrated Clinic 12 Irwin Ave, Suite 200 Toronto, Ontario jiselle@healthhubclinic.com John David Millar, BSc, ND Jacksoncreek Natural Health Centre 187 Sherbrooke St. Peterborough, Ontario naturo@jacksoncreek.ca Jordan Robertson, BSc, ND Lakeshore Clinic 2159 Lakeshore Road Burlington, Ontario L7R 1A5 jordanrobertsonnd@gmail.com Judah Bunin, BSc, MSc, ND, DrAc Fredericton Naturopathic Clinic 10-150 Cliffe St Fredericton, New Brunswick E3A0A1 frednatclin@yahoo.ca

December 2014 | www.ihpmagazine.com

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Rajesh Ragbir, ND Scarborough Naturopathic Clinic 1585 Markham Road, Suite 211 Scarborough, Ontario M1B 2W1 ragbir.nd@gmail.com Raza Shah, BSc, ND St. Jacobs Naturopathic 1-9 Parkside Drive St. Jacobs, Ontario N0B 2NO stjacobs.nd@gmail.com Rochelle Wilcox, BA, ND Living Well Integrative Health Centre 2176 Windsor Street Halifax, Nova Scotia B3K 5B6 drwilcox@balancehealthcentre.ca

Tanya Lee, BSc, ND The Health Centre of Milton 400 Main St East Suite 210 Milton, Ontario L9T 1P7 tanyalee.nd@gmail.com Terry Vanderheyden, ND Bayside Naturopathic Medicine 118 Bay Street Barryâ&#x20AC;&#x2122;s Bay, Ontario KOJ 1B0 doctrv@gmail.com Theresa Jahn, BSc, ND Living Well Integrative Health Centre 2176 Windsor Street Halifax, Nova Scotia B3K 5B6 info@theresajahn.com

editorial board

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

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

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

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

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editorial board

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

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

Kristy Prouse, MD, FRCSC Dr Prouse has practiced as an Obstetrician/Gynaecologist for over 10 years and currently holds the position of assistant professor at the University of Toronto and the Northern Ontario School of Medicine. Dr Prouse completed her medical degree at Queen’s University and residency training at the University of Calgary. Additionally, Dr Prouse has trained in bio-identical hormone replacement therapy and anti-aging and regenerative medicine through the University of Southern 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

Meditation 1 Impact on gene expression

By Polina Kapoustina, ND (Cand)

December 2014 | www.ihpmagazine.com

Polina Kapoustina, BA, ND (cand) Canadian College of Naturopathic Medicine Clinic Intern, Robert Schad Naturopathic Clinic 1255 Sheppard Avenue East, Toronto, Ontario, M2K 1E2

Abstract There is growing evidence to demonstrate that mind-body practices, such as yoga and meditation, can influence our gene expression and in fact counteract cellular damage that may be induced by states of chronic stress. The changes in genetic expression, as a result of doing these mind-body exercises to elicit the “relaxation response,” a physiological and psychological state that is opposite to the fight-or-flight response, play a significant role in reducing the body's inflammation and states of anxiety. Clinically, this applies to a variety of treatment approaches including heart disease, mental health, autoimmune disease and cancer. These findings highlight the importance of a mind-body "prescription" in medicine and provide tangible data to reaffirm the benefits of what has been practiced for centuries in various parts of the globe.

Background There is increasing awareness as well as research to show the negative impacts of chronic stress on health. On the other hand, we are just starting to discover what is occurring on a molecular level in a relaxed state. The “relaxation response” (RR) is defined as a physiological and psychological state that is opposite to the stress or fight-or-flight response (Bhasin 2013). The RR can be elicited through multiple mind-body approaches such as yoga, mediation, tai chi, qi gong, progressive muscle relaxation, biofeedback, and breathing exercises (Bhasin 2013). The common thread between these techniques is two-fold: (1) the focus on a word, sound, phrase, repetitive prayer, or movement and (2) the disregard of everyday thought. These two steps are critical in breaking the train of everyday thinking and influencing physiological changes including decreased oxygen consumption and carbon dioxide elimination, changes in blood pressure, heart and respiratory rate, norepinephrine responsiveness, increased heart rate variability, and alterations in cortical and subcortical brain regions (Bhasin 2013). Practices such as yoga and meditation have been in use for over 5000 years in India (Qu 2013), but there still remain questions around their biological effects on our health as well as how yoga compares to other types of exercise. Recent evidence shows that meditation practices influence our biology through epigenetic changes. Epigenetic changes involve modifications of gene expression and transcription, with the potential to affect virtually any cell in the body through alterations in cell membrane receptor expression and/ or various signaling 58

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factors. Due to these pervasive and farreaching effects, meditation practices have the potential to modify chronic disease risk and progression, including heart disease, mood disorders, and autoimmune disorders, and cancer. Current studies are looking at how short and long-term meditation practitioners may regulate immunity, metabolic rate, and response to oxidative stress (RavnikGlavac 2012). Such new knowledge helps us understand the best therapeutic applications of meditation, and helps reinforce its importance as an intervention for practitioners and patients alike. This paper will examine the current evidence seeking to elucidate the biological effects of meditation practices.

Clinical Trials Dusek et al. (2008) provide evidence that a RR practice results in genomic expression alterations in healthy subjects. Sustained genetic expression alterations were found in both short-term (N2 group) and longterm meditators (M group) when compared to novices (N1). These types of changes are significantly linked to oxidative phosphorylation, antigen processing and presentation, and apoptosis (Dusek 2008). The authors conclude that regular daily practice is recommended for sustained beneficial effects. Ravnik et al. (2012) further show that a higher state of consciousness is associated with significant changes in gene expression and brain waves. Table 1 shows a summary of results from their study that followed two long-term meditators (20+ years experience) for one year. Their results showed that a higher state of consciousness is characterized by both down-regulation and up-regulation of various

The Journal of IHP

Table 1. Human trials demonstrating the use of yoga practice and its affect on gene expression Reference

Method

Outcome

Qu 2013

Prospective study N = 10, male, 18-50 yo, no chronic disease, good psyc health, in Germany, with previous yoga experience (up to 5 yrs)

Peripheral blood mononuclear cells (PBMCs) were isolated from blood sample, taken right before and after the activities, for gene expression profiling experiments. Rapid changes (within 2 hours) were found in PBMCs of yoga group. 97 unique genes were affected in yoga group vs. 24 in control. Hence a yoga program may have additional health benefits as compared to exercise plus simple relaxation. Effects are global and not specific to molecular pathways.

Sudarshan Kriya (SK) yoga program (postures, breathing, meditation) or control regimen (nature walk with relaxing music) x 4 consecutive days, 6:30-8:30am every day Black 2013

RCT N = 45 familial dementia caregivers 12 mins daily Kirtan Kriya meditation (KKM) or12 mins daily relaxing music (RM) x 8 weeks Genome-wide transcriptional profiles were collected at baseline and 8-week mark.

Bhasin 2013

Prospective (novices) and cross-sectional (long-term practitioners) study N = 52: 26 healthy subjects (in Boston, USA) with no RR experience (N1, N2) AND 26 healthy subjects with experience of 4-20 years (M) 20mins CD of Relaxation Response (RR) activity: yoga/ meditation/ qi gong/ tai chi/ progressive /biofeedback/ breathing exercises or 20mins of health education CD (control) x 8 weeks Blood was collected immediately prior, immediately after and 15min after activity, isolating total RNA. FeNO was measured using a rapid response chemoluminescent Nitric Oxide Analyzer.

Ravnik- Glavac 2012

Preliminary cross-sectional study N = 2 long-term (20+ years) meditation (using Zen, Kriya goa, Kundalini yoga, and Pranayama x 25 min; eyes open or closed) practitioners followed over 1 year. Age 40-50s, Male, Caucasian EEG – to measure brain frequencies – during rest and meditation, every 50 seconds Blood sample – control samples (non-meditating days) and test sample (1h and 15 after meditation) – total RNA isolation performed; analyzed transcription differences b/w different states of consciousness via micro array analysis

Dusek 2008

N= 58 healthy subjects (19 long term practitioners (M); 19 control (N1); 20 newly trained (N2)) Listened to 20mins of RR CD daily for 8 weeks Blood transcriptional profiles assessed.

Reduced activity of pro-inflammatory NF-kB and increased interferon response factors. The KKM group showed significantly lower levels of depressive symptoms and greater improvement in mental health compared with the RM group following the intervention. In KKM, 65.2% of the participants showed 50% improvement on the Hamilton Depression Rating scale, and 52% showed 50% improvement on the Mental Health Composite Summary score of the Short Form-36 scale. In RM, 31.2% of the participants showed 50% improvement on the Hamilton Depression Rating scale. 19% showed 50% improvement on the Mental Health Composite Summary score of the Short Form-36 scale. These proportions were significantly different across condition (p<0.05). Instant increases in FeNO after 20-minute RR elicitation among short-term (N2) and long-term (M) practitioners and the sustained increase 15 minutes later in the M group. Long-term RR practitioners have more transcriptional changes as compared to short-term practitioners at rest. Up-regulated long-term changes induced by RR are linked to telomerase stability and maintenance. RR progressively affected energy metabolism and inflammation pathways. Gene sets for CYP450 family, steroid hormones, retinol metabolism, and cell adhesion pathways were up-regulated in M and N2 with greater enrichment in M. Gene sets linked to energy metabolism (electron transport chain, integration of energy metabolism) and insulin secretion pathways were also up-regulated in M compared to N1 and N2. EEG: Increased signal power in theta (4-7Hz) and alpha (8-12 Hz) brain frequencies during meditation, mainly in parieto-occipital and frontal regions. Genetic analysis: Down regulation of metabolic and cell cycle processes, signaling, protein transport, regulation of gene expression, DNA repair, epigenetic mechanisms. Immune system activity, apoptotic processes were both up and down-regulated, as well as the response to stress. Up-regulation of genes involved in hemoglobin synthesis, transport of oxygen and nitric oxide, significantly enrichment in glutamate transport, ionotropic glutamate receptor activity, and NADH dehydrogenase activity. Significant alterations in cellular metabolism, oxidative phosphorylation, generation of reactive oxygen species and response to oxidative stress in long-term and short-term practitioners of daily RR practice that may counteract cellular damage related to chronic psychological stress.

December 2014 | www.ihpmagazine.com

genes, including down-regulation of the stress response, up-regulation of genes involved in hemoglobin synthesis, transport of oxygen and nitric oxide, and enrichment in glutamate transport, glutamate receptor activity, and NADH dehydrogenase activity. Brain EEG showed that there was an increase in theta and alpha brain frequencies during a meditative state. This study does have a small sample size and may not apply to novice meditators, but the results are statistically significant and it is at present the only study that has evaluated brain waves. Long-term meditation practitioners were chosen in this case, according to the authors, in order to isolate the expression changes of a higher state of consciousness, however this does not mean that benefits would be absent among novice practitioners. Bhasin et al. (2013) studied the acute changes in gene expression that took place within a single session of a RR-eliciting practice. 60

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Over an 8-week period, healthy novice subjects were exposed to 20 minutes of any of the following mind-body interventions: yoga/ meditation/ qi gong/ tai chi/ progressive / biofeedback/ breathing exercises. Fractional exhaled nitric oxide (FeNO) samples were collected at three time points during each session to explain the physiological effects of RR including reduction in blood pressure. FeNO is known to play a prominent role in vascular dilatation (Bashin 2013). This study showed that a relaxed state influences various pathways via mitochondrial signaling. Subjects experienced down-regulation of the NF-kB pathway, mitigating oxidative stress, inflammation, and chronic disease vulnerability. Qu (2013) also looked at the immediate changes that occur within two hours of yoga for four consecutive days. This study showed that yogic practices have rapid effects at the molecular level in circulating immune cells.

The Journal of IHP

Practices such as yoga and meditation have been in use for over 5000 years in India, but there still remain questions around their biological effects on our health as well as how yoga compares to other types of exercise.

1 All the studies described thus far have been prospective or cross-sectional. However, a randomized control trial (RCT) conducted in 2013 investigated a unique population group experiencing chronic stress: caregivers of elderly family members with dementia. This was defined as caring for the family member for at least three days per week. Caregivers often report lower levels of satisfaction with life than healthy controls, showing higher markers of inflammation such as C-reactive protein and IL-1 receptor antagonist, and reduced levels of cellular immunity such as interferon (IFN) (Black 2013). This RCT tested whether a daily yogic meditation intervention could reverse a pattern of pro-inflammatory and anti-antiviral leukocyte transcriptional alterations induced by stress. Results showed a reduction in the activity of proinflammatory NF-kB and increased interferon response factors (IRF) (Black 2013). The authors concluded that eight weeks of structured daily yogic meditation reversed the pattern of increased NF-κB-associated pro-inflammatory gene expression and decreased expression of IRF1-associated genes.

Future Directions In summary, there is a growing body of evidence to show that

References Bhasin MK, Dusek JA, Chang BH, Joseph MG, Denninger JW, Fricchione GL, Benson H, Libermann TA. Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways. PLoS One. 2013 May 1;8(5):e62817. Black DS, Cole SW, Irwin MR, Breen E, St Cyr NM, Nazarian N, Khalsa DS, Lavretsky H. Yogic meditation reverses NF-κB and IRF-related transcriptome dynamics in leukocytes of family dementia caregivers in a randomized controlled trial. Psychoneuroendocrinology. 2013 Mar;38(3):348-55.

mind-body practices such as yoga and meditation indeed influence our gene expression and counteract cellular damage induced by chronic stress. More questions still remain: are there certain populations or individuals this kind of practice can make a bigger impact? How do we measure one’s progress in clinical practice based on this information (how much, how often, what type of activity and technique, alone or in a group, how advanced)? Could individual genetic backgrounds influence the ability to achieve higher state of consciousness? Nonetheless, we now know that the changes in genetic expression as a result of doing mind-body exercises to elicit the relaxation response, both over short and long-term, can play a role in general health but also in specific diseases by reducing inflammation, hypertension (via FeNO vasodilation), and influence states of anxiety. The potential to alter gene expression profiles of circulating immune cells toward a less pro-inflammatory profile is impressive. Clinically this could also have significant implications in treatment approaches of autoimmune disease, cancer and chronic infections. These findings highlight the importance of not underestimating a mind-body prescription: the importance of taking time to destress and bring one’s awareness to the present moment.

Dusek JA, Otu HH, Wohlhueter AL, Bhasin M, Zerbini LF, Joseph MG, Benson H, Libermann TA. Genomic counter-stress changes induced by the relaxation response. PLoS One. 2008 Jul 2;3(7):e2576. Qu S, Olafsrud SM, Meza-Zepeda LA, Saatcioglu F. Rapid gene expression changes in peripheral blood lymphocytes upon practice of a comprehensive yoga program. PLoS One. 2013 Apr 17;8(4):e61910. Ravnik-Glavač M, Hrašovec S, Bon J, Dreo J, Glavač D. Genome-wide expression changes in a higher state of consciousness. Conscious Cogn. 2012 Sep;21(3):1322-44.

December 2014 | www.ihpmagazine.com

Lifestyle Genomics

The Next Step to Individualized Medicine

By Mansoor Mohammed, BSc (Hons Mol Gen), PhD, Robyn Murphy, ND, Emily Fitzgerald, ND, and Christopher Habib, ND

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The Journal of IHP

Mansoor Mohammed, BSc (Hons Mol Gen), PhD CEO and Co-Founder Younique Genomics 64 Prince Arthur Avenue mansoorm@youniquegenomics.com Robyn Murphy, ND Associate Medical Director Younique Genomics 64 Prince Arthur Avenue robyn@youniquegenomics.com Emily Fitzgerald, ND Clinician Liaison Officer Younique Genomics 64 Prince Arthur Avenue emily@youniquegenomics.com Christopher Habib, ND Clinic Director Mahaya Forest Hill 102-73 Warren Road Toronto, ON M4V 2R9 info@chrishabibnd.com

Abstract Genetics has classically been defined as the study of single genes and the proteins they encode. By extension, born from the fruition of the Human Genome Project, the newer field of genomics encompasses the totality of genes inherited by an individual, the architecture and order of these genes, their encoded proteins, geneto-gene interactions, and the factors that affect their expression. Through advancements in human genomics and DNA sequencing technologies, entire individual genomes have now been sequenced and studied. These studies have highlighted numerous interindividual gene and genomic variations, many with significant functional implications to the myriad of cellular and physiologic pathways necessary for optimal health. Importantly, from a geographic, population and ethnic perspective, human genomic variations appear to have often been ‘cultivated’– evolved, inherited and transmitted– within the context of unique lifestyles, nutrition and environments. Alternately, one may say that unique lifestyles and nutrition have evolved in the context of unique genomic variations and environments. It appears to be a truism that the healthiest individuals are those that have adopted lifestyle and nutrition (henceforth collectively referred to as lifestyle) practices optimized for their individual genomic legacy and environment. This axiom has served as the foundation of a new field in human genomics and medicine referred to as lifestyle genomics.

Introduction Lifestyle genomics is the study of how an individual’s unique genomic legacy converges with lifestyle and environment, to contribute to health and wellbeing. It provides the framework of a refreshed perspective of lifestyle recommendations and guidelines that focuses on the individual. It introduces a perspective of healthcare more inclined to wellness and maintenance of health, as opposed to the default reactive, and symptom-based approach, that so often defines modern conventional medicine. Lifestyle genomics acknowledges that most human diseases are in reality chronic diseases, and that the symptomatic presentation of disease is most often on a continuum that begins with health, progresses through early, and often missed, pathway/cellular/systemic dysfunction (henceforth collectively referred to as pathway dysfunction), escalates to measurable and observable symptoms, and culminates in disease. The insights gleaned from lifestyle genomics facilitate an earlier intervention into this continuum by recommending lifestyle, and where possible, environmental

choices that are in optimal harmony with the genomic legacy of individuals. This paper is the first of a series to introduce lifestyle genomics as it applies to a paradigm shift in health and the practice of integrative and functional medicine. The Canadian Institute of Health Information (CIHI) notes that Canada spends about 11% of its gross domestic product (GDP) on health every year (CIHI 2014). The CIHI further notes that in 2014 this number is expected to work out to approximately $215 billion or about $6000 per Canadian. Not surprisingly, the lion’s share of this spend is toward treating chronic disease. Chronic diseases, the treatment of them, and their societal and fiscal impact on our communities, are the single most crippling component on our healthcare system (Duke Medicine 2005). It is clear that if we are going to lessen the burden on our healthcare system, our efforts must be focused on stemming the tide of chronic diseases. Importantly, we must also acknowledge and remedy the circumstances that have perpetuated their rise. December 2014 | www.ihpmagazine.com

The pharmacology revolution of the past few decades has provided a wealth of medications and treatment options for numerous health concerns and disease eventualities. It is undeniable that this cornucopia of pharmacologic agents has saved countless lives and dramatically improved our ability to treat acute health concerns. While these pharmacologic advancements have dramatically improved emergency medicine, they have inadvertently played a less stellar role in overall population health. The increasing reliance of conventional medicine on drug intervention has shifted the healthcare paradigm from engendering healthy communities and populations, to reactive, symptom-based solutions to disease. As populations, it appears that we no longer focus on maintaining health and wellbeing, but rather, are naively comforted by the thought that when we are ill we can be effectively treated. This philosophy has proved fertile for the development of chronic diseases. By anchoring our approach to healthcare on the symptomatic treatment of disease, we allow actual etiologies to go unnoticed and pathway dysfunctions – the very hallmarks of chronic disease – to thrive. Any purposeful plan to stem the tide of chronic diseases must acknowledge that most begin with health, progress through pathway dysfunctions, and culminate with symptomatic disease. Tellingly, the first echoes of pathway dysfunctions often go unnoticed – both from a symptomatic perspective as well as from being camouflaged within the normal reference ranges of the biomarkers we rely upon as ‘health barometers’. To be clear, biomarker reference ranges are valuable guidelines of normative physiologic functions at the population level. However, many fail to take into consideration the full impact of interindividual and inter-ethnic variations, and yet many more are simply out-dated (Stats Canada 2014). Early physiologic dysfunctions may not alter biomarker readings sufficiently enough for 64

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conventional medicine to recognize the often subtle transition from health to dysfunction, and ultimately to bona fide disease. Therefore, we contend that an over-reliance on generic, and sometimes out-dated, laboratory reference ranges has also become culpable in the perpetuation of chronic diseases. With the aforementioned in mind, it is clear that any strategic approach to addressing the epidemic of chronic disease must be deeper and more purposeful than a reactive symptom-based mode. In fact, any real solution must intervene in the health-disease continuum well before symptoms occur, and ideally at the root of pathway dysfunction. This can only be fully accomplished by appreciating the impact of genomic variations, and their implications, when considered in the context of an individual’s unique lifestyle and environment. It is not surprising that world leaders in medicine are abandoning the “one size fits all approach”, acknowledging the interaction between genetic variants and environment – lifestyle genomics – to adopt proactive, predictive and personalized healthcare.

Lifestyle genomics in the practice of medicine Fewer health concerns define the need for proactive, predictive, and personalized intervention as does cardiovascular disease. Cardiovascular disease has classically been cited as an example of chronic disease and is often the end manifestation of pathway dysfunctions related to vascular health. Evidence links endothelial dysfunction to increased risk factors for the development of cardiovascular disease, including: atherosclerosis, coronary heart disease, hypertension and diabetes (Tian 2012). Lifestyle genomics establishes the principles to uncover the underlying perturbations of cellular health in the context of lifestyle and environment. It allows integrative clinicians

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In the case of John Smith, several lifestyle choices are in obvious disharmony with his genomic legacy and directly contribute to his symptomatic presentation and cascade down the health-disease continuum.

to intervene themselves in the health-disease continuum prior to bona fide disease. To understand and gain a deeper appreciation of lifestyle genomics in the practice of medicine, the hypothetical case of John Smith is presented.

Case example John Smith is a 45-year-old Caucasian male who presents to the clinic with a BMI of 33, history of hypertension and hypercholesterolemia, and a significant family history of cardiovascular disease and dementia. John is a highly successful businessman who, more often than not, enjoys alcoholic beverages daily after work, with more than 5 servings on a typical Friday. He considers himself a social smoker that “can quit anytime” and consumes the typical Standard American Diet (SAD) with 4-6 cups of coffee per day. John Smith is otherwise sedentary, except during his weekend warrior intensive aerobic workouts, aimed to curtail his ever more noticeable abdominal girth. He has noticed that post-work out fatigue associated with his weekend binge training has progressively worsened with age. In addition, he complains of his propensity to ‘catch the latest bug’, which he attributes to his high stress work environment. It is undeniable that John Smith is positive for a number of risk factors associated with the development of cardiovascular disease, which will likely progress into bona fide disease without appropriate intervention.

the latter as a sign that he is ‘working out well’. Overall, these recommendations meet the criteria of conventional symptombased approaches guided by general biomarker parameters of health. However, they fail to truly take the individuality of John Smith into consideration – the convergence of his unique genomic legacy with his lifestyle and environment.

Lifestyle genomics An incorporation of lifestyle genomic insights elevates John Smith from being a generic 45-year-old Caucasian male with biomarkers of (impending) cardiovascular disease to being the John Smith with a unique genomic legacy that is not in optimal harmony with his chosen lifestyle. Some of the most notable genomic variations that relate to endothelial dysfunction and vascular disease, involve: endothelial nitric-oxide synthase (NOS3), angiotensin-converting enzyme (ACE), mitochondrial superoxide-dismutase (SOD2), cytochrome P450 1A2 (CYP1A2), and the two major subtypes of the glutathione-Stransferase (GST) family, theta and mu (GSTT1, GSTM1).

John Smith’s genotypes: Gene

Genotype

Functional Consequence

NOS3

G/T

30% reduction in enzyme activity

ACE

D/D

Increased RAAS activity

SOD2

T/T

70% reduction in enzyme activity

Conventional approach

CYP1A2

C/C

Slow metabolizer

The conventional approach for John Smith’s presentation is likely to be a combination of pharmaceutical interventions combined with general cautionary guidelines toward lifestyle choices. During an initial workup, John Smith is prescribed an ACE inhibitor (Lisinopril) and lipid-lowering medication (Simvastatin) aimed at reducing the symptomatic presentation of hypertension and hypercholesterolemia. John is advised to discontinue smoking, reduce his alcohol consumption to no more than 2 servings per day, lose weight and incorporate more vegetables into his diet, while reducing salt and saturated fat intake. Many of the suggestions, though noteworthy, enter the ears of John Smith as purely generic, which he has heard before without serious consideration or application. He translates the advice to lose weight into increasing his weekend aerobic and gym sessions, despite overwhelming post-workout fatigue. He actually perceives

GSTT1/M1

Null

Absent production of theta and mu GST enzymes

Reviewing the function of these genes and the specific impact of John Smith’s genomic variations on his endothelial function and overall cardiovascular health, quickly reveals key pathway dysfunctions and facilitates a much more personalized approach to his health management. It is notable that John Smith’s symptomatic presentation was in reality rooted in his predisposition for: impaired responses to blood pressure related to NOS3 and ACE; a weakened capacity to manage oxidative stress through ineffective SOD2 activity; and propensity toward vascular inflammation through poor epoxyeicosatrienoid (EET) production and decreased clearance of toxins due to low CYP1A2 activity and significantly compromised GST capacity. December 2014 | www.ihpmagazine.com

Blood pressure regulation NOS3 catalyzes nitric oxide (NO) from L-arginine in response to vascular shear force, relaxing and dilating the arterial smooth muscle to decrease blood pressure. The at-risk T allele of NOS3 (rs1799983) impairs enzymatic activity, reducing NO bioavailability, and is linked to the risk of coronary artery disease (Salimi 2012). ACE modulates blood pressure and sodium reabsorption through the renin-angiotensinaldosterone system (RAAS) by converting angiotensin I to angiotensin II. A restriction fragment length polymorphism in ACE (rs1799752), when deleted, results in the at-risk D allele. D allele carriers demonstrate increased RAAS activity with enhanced sodium sensitivity and increased risk of hypertension (Gard 2010). Oxidative stress and vascular inflammation SOD2 removes reactive oxygen species (ROS) produced in the mitochondria as a function of cellular respiration. Individuals homozygous for the T allele (rs4880) have as much as 70 percent reduction in their enzymatic activity, associated with an increased risk of heart disease and dementia (Tian 2012, Wiener 2007). Reduced SOD2 activity results in increased oxidative damage to the endothelial lining and increased peroxidation of LDL. Combined, these lead to a cascade 66

involving the induction of inflammatory pathways and the localized recruitment of immune cells, which culminate in plaque formation (Tian 2012). CYP1A2, a cytochrome P450 enzyme involved in phase I detoxification, is commonly known for its role in caffeine metabolism. However, it also converts arachidonic acid to EET, an important cardio-protective substrate involved in antiinflammatory and pro-fibrinolytic pathways (Spector 2004). C allele (rs1800497) carriers are slow metabolizers and have a reduced ability to metabolize caffeine and a reduced ability to produce EET. The reduction of caffeine clearance and EET production are both associated with an increase in several CVD risk factors, including hypertension and CAD (Beesley 2007, Palatini 2009). Phase I enzymes work in concert with phase II conjugation enzymes, including the GST family, to play a key role in protecting cells against oxidative and inflammatory stress caused by toxins and xenobiotics (Dusinkska 2001). Despite being the most important members of the GST family, the genes for the theta and mu enzyme subtypes are sometimes completely missing from individuals. This interesting phenomenon can be traced through family lines and has been found in relatively significant frequencies in some populations. The absence of these genes, referred to as null genotypes of GSTT1 and GSTM1, is strongly associated with poor clearance

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of toxins and ROS and with increased risk of CHD (Du 2012, Frova 2006).

Informed lifestyle and therapeutic intervention through genomics By determining an individual’s unique genomic variations and assessing their functional implications in light of lifestyle and environment, the clinician gains powerful insights into pertinent aspects of the health-disease continuum. In the case of John Smith, several lifestyle choices are in obvious disharmony with his genomic legacy and directly contribute to his symptomatic presentation and cascade down the health-disease continuum. John can now appreciate lifestyle recommendations in light of their specific relevance to his unique genomic legacy. Recommendations to reduce salt, saturated fats, and caffeine consumption, are now personalized in the context of his unique genomic variations and his specific need to curtail vasculature stress and oxidation of LDL particles. Beyond the ‘cigarette box warnings’, John can now appreciate that his social smoking is in specific and dangerous disharmony with his innate detoxification capabilities (or in his case, incapability). Smoking induces the CYP1A2 gene, which ironically enhances the pro-toxin transformation of circulating polycyclic aromatic hydrocarbons (PAH) and heterocyclic amines (HAA) (abundant in tobacco smoke), both of which are associated with an increase in oxidative stress and deregulation of cellular signaling pathways (Wang 2011). John now understands that one of his body’s most important pathways to combat oxidative stress and facilitate toxin elimination is missing. Typically, GST enzymes compensate for redox-imbalance and toxic overload through glutathione conjugation. However, GSTM1 and T1 null individuals are at a marked risk of oxidative damage with significant increased risk for cardiovascular disease (Maurya 2010, Wang 2010). To compensate for John’s unique genomic variations, consumption of cruciferous vegetables containing isothiocyanates and supplementation of n-acetylcysteine are shown to interact positively with GST null genotypes, reducing inflammatory cytokines (NF-κB and IL-6) and increasing total anti-oxidation to reduce risk of cardiovascular disease (Dyba 2010, Moradi 2009, Navarro 2009). Anti-atherogenic, antithrombotic and anti-inflammatory pathways can be further supported through omega-3 polyunsaturated fatty acids (n-3 PUFA). Recent studies have demonstrated that NOS3 T allele carriers respond significantly better to n-3 PUFAs to improve lipid profiles and reduce cardiac mortality, which is further enhanced by concomitant statin therapy (Ferguson 2010, Psota 2006). With respect to exercise and John Smith’s propensity toward vascular inflammation, it would be more adventitious to encourage low impact training to limit inflammatory cytokines (IL-6, CRP) and ROS production, otherwise induced by heavy aerobic exercise (Biljani 2005, Chen 2014). The above regiment offers personalized genotype-based diet, lifestyle and supplement recommendations, consistent with

John’s specific genomic legacy. The recommendations are simple, yet purposefully resonant with his unique genomic variations and are tailored to optimize the convergence of his genomic make-up, lifestyle and environment.

Pharmacogenomics While insights through lifestyle genomics elevate clinical discourse through simple, yet meaningful lifestyle modulations, genomic variations also guide conventional pharmaceutical therapy. Pharmacogenomics identifies meaningful gene-drug interactions that directly influence dosage strategies, side-effect profiles and patient response. Research shows that D allele carriers of the ACE gene have lower mean blood pressure with the treatment of ACE-inhibitors compared to the I/I genotype (Chung 2010). The SLCO1B1 gene (rs4149056), which mediates intrahepatic transport of pharmaceutical agents, alters the risk of statin-induced myopathy. Those who are C allele carriers are at a significantly higher risk of myopathy with simvastatin use (Brunham 2012). In the case of John Smith, he is an ideal candidate for lisinopril; however, the status of his SLCO1B1 gene may deter simvastatin pharmacotherapy. Genomic testing facilitates a far more individualized approach to pharmaceutical intervention and combines the best of conventional and integrative medicine

Conclusion and ancient wisdom Conventional medicine fosters the development of chronic diseases through a symptom-based approach to medicine, which fails to recognize individuality relies heavily on drug intervention. Overly generic and out-dated population statistics define normality through biomarker parameters, which ignore individual genomics and the effects of environment and lifestyle interactions. Lifestyle genomics returns health and wellbeing to the individual, cognisant of their unique genomic legacy and its convergence with lifestyle and the environment. It recognizes that functional inefficiencies of biologic pathways, associated with genomic variations, may be ameliorated through the adoption of meaningful lifestyle practices, which are cultivated and passed down through ancient traditions. When cultures embrace lifestyle choices that harmonize with their inherent genomic legacies, pathway dysfunctions are less impactful on overall health. Through lifestyle genomics, integrative and functional medicine moves closer to its goal of maintaining health and addressing underlining etiologies. Clinicians are able to support proactive, predictive and individualized healthcare, to intervene at the first signs of dysfunction along the health-disease continuum. In fact, at its fruition lifestyle genomics provides the template by which a priori lifestyle and environment choices might mitigate or dramatically reduce pathway dysfunction. Author Disclosures Mansoor Mohammed, BSc (Hons Mol Gen), PhD, Robyn Murphy, ND, Emily Fitzgerald, ND, work for Younique Genomics. Christopher Habib, ND, offers the services of Younique Genomics to his patients in his private practice. December 2014 | www.ihpmagazine.com

References Beesley J, Jordan SJ, Spurdle AB, Song H, Ramus SJ, Kjaer SK, Hogdall E, DiCioccio RA, McGuire V,Whittemore AS, Gayther SA, Pharoah PD, Webb PM, Chenevix-Trench G; Australian Ovarian CancerStudy Group; Australian Cancer Study (Ovarian Cancer); Australian Breast Cancer Family Study. Association between single-nucleotide polymorphisms in hormonemetabolism and DNA repair genes and epithelial ovarian cancer: resultsfrom two Australian studies and an additional validation set. Cancer Epidemiol Biomarkers Prev. 2007;16(12):2557-65. Biljani RL, Vempati RP, Yadav RK, Ray RB, Gupta V, Sharma R, Mehta N, Mahapatra SC. A brief but comprehensive lifestyle education program based on yoga reduces risk factors for cardiovascular disease and diabetes mellitus. J Altern Complement Med. 2005;11(2):267-74. Brunham LR, Lansberg PJ, Zhang L, Miao F, Carter C, Hovingh GK, Visscher H, Jukema JW, Stalenhoef AF, Ross CJ, Carleton BC, Kastelein JJ, Hayden MR. Differential effect of the rs4149056 variant in SLCO1B1 on myopathyassociated with simvastatin and atorvastatin. Pharmacogenomics J. 2012;12(3):233-7. Chen YW, Apostolakis S, Lip GY. Exercise-induced changes in inflammatory processes: Implications for thrombogenesis in cardiovascular disease. Ann Med. 2014;46(7):439-55. Chung CM, wang RY, Chen JW, Fann CS, Leu HB, Ho HY, Ting CT, Lin TH, Sheu SH, Tsai WC, Chen JH, Jong YS, Lin SJ, Chen YT, Pan WH. A genome-wide association study identifies new loci for ACE activity: potential implications for response to ACE inhibitor. Pharmacogenomics J. 2010;10(6):537-44. CIHI. National Health Expenditures. 2014. Retrieved November 26, 2014, from Canadian Institute of Health Information: http://www.cihi.ca/web/ resource/en/nhex_2014_pubsum_en.pdf Du Y, Wang H, Fu X, Sun R, Liu Y. GSTT1 Null genotype contributes to coronary heart disease risk: a meta-analysis. Mol Biol Rep. 2012;39(9):3571-9. Duke Medicine. Duke Medicine, 2005. Retrieved Nov 26, 2014, from Chronic Disease Management Crippling Primary Care System: http://corporate. dukemedicine.org/news_and_publications/news_office/news/8839 Dusinská M, Ficek A, Horská A, Raslová K, Petrovská H, Vallová B, Drlicková M, Wood SG, Stupáková A,Gasparovic J, Bobek P, Nagyová A, Kováciková Z, Blazícek P, Liegebel U, Collins AR. Glutatione S-transferase polymorphisms influence the level of oxidative DNA damage and antioxidant protection in humans. Mutat Res. 2001;482(1-2):47-55. Dyba M, Wang A, Noone AM, Goerlitz D, Shields P, Zheng YL, Rivlin R, Chung FL. Metabolism of isothiocyanates in individuals with positive and null GSTT1 and M1 genotypes after drinking watercress juice. Clin Nutr. 2010;29(6):813-8. Ferguson JF, Phillips CM, McMonagle J, Perez-Martinez P, Shaw DI, Lovegrove JA, Helal O, Defoort C, Gjelstad IM, Drevon CA, Blaak EE, Saris WH, Leszczynska-Golabek I, Kiec-Wilk B, Riserus U, Karlstrom B, Lopez-Miranda J, Roche HM. NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease and interact with omega-3 polyunsaturated fatty acids. Atherosclerosis. 2010;211(2):539-44. Frova C. Glutathione transferases in the genomics era: new insights and perspectives. Biomol Eng. 2006;23(4):149-69. Gard PR. Implications of the angiotensin converting enzyme gene insertion/ deletion polymorphism in health and disease: a snapshot review. Int J Mol Epidemiol Genet. 2010;1(2):145-57.

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Maurya PK, Rizvi SI. Age-dependent changes in glutathione-s-transferase: correlation with total plasma antioxidant potential and red cell intracellular glutathione. Indian J Clin Biochem. 2010;25(4):398-400. Moradi M, Mojtahedzadeh M, Mandegari A, Soltan-Sharifi MS, Najafi A, Khajavi MR, Hajibabayee M, Ghahremani MH. The role of glutathione-Stransferase polymorphisms on clinical outcome of ALI/ARDS patient treated with N-acetylcysteine. Respir Med. 2009;103(3):434-41. Navarro SL, Chang JL, Peterson S, Chen C, King IB, Schwarz Y, Li SS, Li L, Potter JD, Lampe JW. Modulation of human serum glutathione S-transferase A1/2 concentration by cruciferous vegetables in a controlled feeding study is influenced by GSTM1 and GSTT1 genotypes. Cancer Epidemiol Biomarkers Prev. 2009;18(11):2974-8. Palatini P, Ceolotto G, Ragazzo F, Dorigatti F, Saladini F, Papparella I, Mos L, Zanata G, Santonastaso M. CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. J Hypertens. 2009;27(8):1594-601. Psota TL, Gebauer SK, Kris-Etherton P. Dietary omega-3 fatty acid intake and cardiovascular risk. Am J Cardiol. 2006;98(4A):3i-18i. Salimi S, Naghavi A, Firoozrai M, Zand H, Tavilani H, Nahkhaee A, Mohebbi A. Association of plasma nitric oxide concentration and endothelial nitric oxide synthase T-786C gene polymorphism in coronary artery disease. Pathophysiology. 2012;19(3):157-62. Spector AA, Fang X, Snyder GD, Weintraub NL. Epoxyeicosatrienoic acids (EETs): metabolism and biochemical function. Prog Lipid Res. 2004;43(1):55-90. Tian C, Liu T, Fang S, Du X, Jia C. Association of C47T polymorphism in SOD2 gene with coronary artery disease: a case-control study and metaanalysis. Mol Biol Rep. 2012;39(5):5269-76. Wang H, Yamamoto JF, Caberto C, Saltzman B, Decker R, Vogt TM, Yokochi L, Chanock S, Wilkens LR, Le Marchand L. Genetic variation in the bioactivation pathway for polycyclic hydrocarbons and heterocyclic amines in relation to risk of colorectal neoplasia. Carcinogenesis. 2011;32(2):203-9. Wang J, Zou L, Huang S, Lu F, Lang X, Han L, Song Z, Xu Z. Genetic polymorphisms of glutathione S-transferase genes GSTM1, GSTT1 and risk of coronary heart disease. Mutagenesis. 2010;25(4):365-9. Wiener HW, Perry RT, Chen Z, Harrell LE, Go RC. A polymorphism in SOD2 is associated with development of Alzheimer’s disease. Genes Brain Behav. 2007;6(8):770-5. Williams RJ, Spencer JP. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radic Biol Med. 2012;52(1):35-45.

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3 Chemotherapy and RadiationInduced Oral Mucositis Integrative management By Meighan Valero, ND

Meighan Valero, ND Be Well: A Creating Wellness Centre 3200 Electricity Drive Windsor, ON N8W 5J1 Ph: (519) 972-9355 Fax: (519) 972-6355

Abstract Oral mucositis is characterized by erythema, inflammation, and ulcerations of the mucous membranes in the oral cavity. This common side effect from radiation and chemotherapy can have significant impacts on quality of life, including alterations in immunity, malnutrition, and weight loss. At present, treatment options for this condition are limited. This review highlights the current state of evidence regarding oral mucositis and treatments that may help prevent or reduce its occurrence. December 2014 | www.ihpmagazine.com

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Introduction Mucositis is a common complication among patients receiving chemotherapy or radiation therapy, occuring in approximately 40% of this population (Raeessi 2014 A). It can be especially problematic during treatment of head and neck malignancies, as well as during treatment with concurrent chemotherapies, which include alkylating agents such as cyclophosphamide and various platinums, anti-tumour antibiotics such as bleomycin, adriamycin (doxorubicin) and epirubicin, and antimetabolites such as 5-fluorouracil (5-FU). Uncontrolled mucositis can profoundly impact quality of life and treatment effectiveness for patients with cancer, as it may lead to dose limitations for cancer therapy. It can cause immense pain, increases the risk of infection and dysphagia, cause difficulty with food and fluid ingestion, affect nutrition and hydration status and lead to weight loss (Keefe 2007, Stubbe 2013, Worthington 2011).

Treatments In addition to good oral hygiene, avoidance of spicy, acidic, hard, and hot foods and beverages, the use of mild-flavoured toothpastes, and repeated mouthwashes with suggested rinses from the patientâ&#x20AC;&#x2122;s local cancer clinic, the following have been shown to be effective in reducing oral mucositis induced by conventional cancer treatment. CHAMOMILE In a recent randomized phase II clinical trial, 40 patients undergoing hematopoietic stem cell transplantation (HSCT) received routine care plus a mouthwash containing a liquid extract of the botanical Chamomilla recutita at 0.5%, 1%, or 2% or standard care alone (control group). Use of the mouthwash ended when the oral mucosa was reestablished or the granulocyte count exceeded 500 mm3 for 3 consecutive days in patients who did not develop mucositis. Control patients received standard care without use of a herbal mouthwash. Patients were evaluated daily using the measurement scale for oral toxicity defined by the World Health Organization. Of the three concentrations, the experimental group at the 1% dosage demonstrated the greatest reduction in incidence, intensity and duration of oral mucositis compared to the control group. Patients tolerated the herbal extract well and it was found to be safe with no moderate or severe adverse effects (Braga 2014).

Table 1. World Health Organization Scale for Oral Mucositis Grade

Description

No oral mucositis

Erythema and soreness

Ulcers, inability to eat foods

Ulcers, liquid diet required

Ulcers, alimentation not possible

Note. Adapted from WHO 1979 70

DGL Deglycyrrhizinated licorice (DGL) is an extract of licorice that has had the glycyrrhetinic acid component removed. This avoids the potential hypertensive properties of glycyrrhetinic acid. DGL is well-known to possess demulcent properties that promote the healing of mucus membranes (Dehpour 1994, Morgan 1982). DGL is available in multiple forms, easily dissolved and is cost-effective. While it does require frequent dosing for effectiveness it has been shown to be clinically beneficial in healing mucus membranes. A number of studies dating from the 1970s to present have demonstrated its usefulness in treating peptic ulcer, aphthous ulcers, as well as radiotherapy induced mucositis. One of the earlier studies reported on the 2-week use of mouthwash containing DGL in the treatment of aphthous ulcers. In this study, DGL provided pain relief and accelerated the healing time of the ulcers (Das 1989). In a more recent study, a randomized, double-blinded clinical trial, subjects with recurrent aphthous ulcers were assigned to receive either a patch with glycyrrhiza root extract, a placebo patch, or no treatment at the onset of a lesion. Treatment with topical glycyrrhiza resulted in improvements in ulcer size (p <0.05) and pain (p <0.01), compared to both the placebo and no-treatment groups (Martin 2008). Other, older clinical trials have compared DGL to carbenoxolone, cimetidine, and ranitidine (Mills 2000, Morgan 1982) and found it to be equally effective in healing gastric and duodenal ulcers. With respect to cancer related mucositis, a couple recent studies demonstrated significant benefit. One clinical trial pertaining to mucositis induced by cancer treatment involved a total of 75 patients who received radiotherapy to the head and neck and were divided into 4 groups: Group A applied licorice powder and honey locally and consumed 10mL of a licorice preparation twice daily; Group B applied licorice powder and honey locally; Group C applied only honey locally; and Group D was the control group which received standard medical treatment for mucositis (Das 2011). Each group received treatment for 7 weeks. Of the four groups, Group A had the greatest reduction in radiation-induced mucositis (p< 0.001) compared to the control group. While this study had many inherent flaws in that the treatment agents were not standardized, and blinding of assessors for the evaluation of mucositis was not used, it is one of only two studies to date published in the literature showing promise of DGLâ&#x20AC;&#x2122;s efficacy in treating radiation-induced mucositis. The second study was a randomized, double blind trial examining the topical use of mucoadhesive patch containing licorice extract (Ghalayani 2014). A total of 60 patients with radiotherapy-induced mucositis were randomized to treatment with a patch containing triamcinolone acetonide or a patch containing licorice. Over consecutive weeks, both groups experienced significant improvements (p<0.05) in the symptoms listed as part of the WHO Mucositis Score (Table 1). There was little change seen in pain ratings however.

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DGL is contraindicated in hormone-sensitive breast, uterine, and ovarian cancer due to its phytoestrogenic effects and may interfere with medications and chemotherapy that rely on cytochrome P450 2B6, 2C9, and 3A4 metabolism (Stolpman 1999).

and swish and spit throughout the day. • ½ tsp salt • ½ tsp baking soda • 1 tablespoon glutamine • 250mL room temperature water

GLUTAMINE Glutamine is the most abundant free amino acid in the human blood stream and is conditionally essential to cells (Chen 2012). It plays a regulatory role in metabolism (oxidative fuel, gluconeogenic precursor, lipogenic precursor), cell integrity (apoptosis and cell proliferation), protein synthesis, and degradation, among other processes (Curi 2005). While many practitioners find great benefit using glutamine as a treatment for mucositis induced by chemotherapy and radiation, existing research shows mixed findings. A 2011 Cochrane review by Worthington et al. evaluated the prevention of oral mucositis and showed no statistically significant benefit of using oral glutamine. The review did find weak but statistically significant evidence for intravenous glutamine in preventing severe mucositis however (Worthington 2011). Smaller trials suggest a benefit for using glutamine during radiation (Savarese 2003) and recommend contact with mucous membranes via a swish and swallow method of administration (Noe 2009, Savarese 2003). A small trial reviewed by Worthington et al. found similar protective effects with intravenous glutamine, 0.4 g/kg weight/day given on chemotherapy days, among patients undergoing chemoradiotherapy for head and neck cancer (Cerchietti 2006). Phase I and II pilot studies on dosage guidelines found that 20 to 30 g daily of glutamine in divided doses was more effective than lower doses (Noe 2009). It is most effective when administered from the start of radiation until 2 weeks after completion. A systematic review by Gibson et al performed in 2013 analyzed the available literature and defined evidence-based clinical practice guidelines for the use of agents used to treat and prevent mucositis. One of the most important findings in this review was the change in guideline in regards to the use of systemic glutamine. Newer literature demonstrates that glutamine may be effective and without severe toxicity. However, due to conflicting evidence at this time, the guidelines were merely changed from “not recommended” to “no guideline possible.” (Stubbe 2013) Due to the fact that cancer produces a state of glutamine deficiency (Guarav 2012) that can be further aggravated by the toxic effects of chemotherapy, common recommendations made by naturopathic physicians with special interests in oncology include 15g swish and swallow twice daily for approximately 5 days after chemotherapy agents such as Taxol for example, and 8-10 days post 5-Fluorouracil (5-FU). Preparation of the following recipe has been shown to help clinically in the prevention and treatment of oral mucositis. Directions are to prepare one glass per day; take frequent sips

Currently, there is controversy regarding whether glutamine may serve as a possible fuel for cancer cells, when orally ingested. As a result, it is generally advised that as a precaution, glutamine should be administered as a swish and swallow formula rather than being swallowed. Limitations of the idea that glutamine may fuel cancer cell growth is that it is based predominantly on in vitro studies, whose generalizability to the complex human body is uncertain (Son 2013). Some have argued that since it is the most abundant amino acid in the body, and is synthesized in vivo when not supplied externally, supplemental glutamine is unlikely to have harmful effects on cancer progression, especially when weighed against the benefits of correcting the state of malnutrition produced by cancer, supporting immune function, and preventing mucositis and neuropathy. Data from higher level evidence appears to support this counter-argument: a retrospective study of patients with stage IIIB non-small cell lung cancer (NSCLC) found that glutamine supplementation (10g 3 times daily) given for the prevention of radiation induced esophagitis was not associated with worse survival metrics or tumor control (Topkan 2012). On the other hand there was significant benefits for preventing radiation esophagitis, weight loss, and associated treatment delays. Nonetheless, it may be prudent that when possible, glutamine supplementation be limited to periods of active chemo- and/ or radiation therapy for the time being. HONEY Honey is an agent that has long been used to soothe mucus membranes. Impressively, a recent systematic review and metaanalysis showed an 80% relative risk reduction in radiationinduced oral mucositis among honey-treated patients when compared with control group (Song 2012). The meta-analysis included three studies in which 120 patients with head and neck cancers receiving radiation therapy were evaluated for radiationinduced mucositis using the WHO (Table 1) and Radiation Therapy Oncology Group (RTOG) criteria (Table 2).

Table 2 Radiation Therapy Oncology Group Scale for Mucositis Grade

Description

No changes over baseline

Erythema

Patchy reaction <1cm, non-contiguous

Confluent reaction >1.5cm, contiguous

Deep ulceration/necrosis and/or bleeding

Note: Adapted from Song 2012 and RTOG 2013.

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In these three studies, honey was applied before, directly after, and several hours after radiation therapy, to the inside of the mouth. The control group did not actively receive treatment for mucositis. The risk of developing mucositis in the honey-treatment group was 80% lower than in the control group (relative risk [RR] 0.19, 95% confidence interval [CI] 0.098-0.371) (Song 2012). The topical application of natural honey is a simple and cost-effective treatment for radiation mucositis that warrants further investigation in large multicentre randomized trials. HONEY PLUS COFFEE In addition to use of honey alone, research has investigated the effect of honey when used in conjunction with coffee, a surprising addition. A recent double-blinded randomized controlled trial evaluated a total of 75 eligible adult patients who were assigned to one of three treatment groups. Each patient was given a syrup-like solution. The first group was given 20 ampoules of betamethasone, each containing 8mg betamethasone. The second group was given 300g of honey only. The third group was given 300g of honey plus 20g of instant coffee. The participants were told to sip 10mL (three teaspoons) of the prescribed product and then swallow it every three hours for one week. The severity of the lesions was clinically evaluated before the treatment as well as one week after the intervention. Results showed that all three treatment regimens reduced the severity of the mucositis lesions, however the greatest reduction in lesion severity was achieved in the honey plus coffee group, followed by the honey only group. The idea to combine coffee plus honey was extrapolated from previous studies performed by the same research team in which they assessed the effect of honey plus coffee on the treatment of persistent post-infectious cough (Raeessi 2014 B, 2013, 2011). In these studies, researchers noted the rapid healing effect of this treatment modality on the lesions in the hypopharynx mucosal membranes, and decided to design a new trial to evaluate the effect of this regimen on oral mucositis induced by cancer chemotherapy (Raeessi 2014 B). The biological basis for this additive effect is unclear, but may be due to possible antioxidant and anti-inflammatory effects (Raeessi 2014 B). LOW LEVEL LASER Finally, a systematic review and meta-analysis by Oberoi et al. found that prophylactic Low Level Laser Therapy (LLLT) was able to reduce severe mucositis and pain in patients with cancer undergoing hematopoietic stem cell transplantation and associated chemo/ radiation. The review included 18 RCTs with 1144 subjects. Results showed that LLLT reduced the overall risk of severe mucositis (RR 0.37, 95%CI 0.20-0.67, p =0.001). When compared to placebo (no therapy), LLLT also reduced severe mucositis at the time of anticipated maximal 72

mucositis (RR 0.34, 95% CI 0.20-0.59), overall mean grade of mucositis (standardized mean difference -1.49, 95% CI -2.02 to -0.95), duration of severe mucositis (weighted mean difference -5.32, 95% CI -9.45 to -1.19), and incidence of severe pain (RR 0.26, 95% CI 0.18 to 0.37) (Oberoi 2014). Increasing supportive evidence for low-level laser therapy has allowed for new guidelines in the prevention of oral mucositis in adult patients receiving hematopoietic stem cell transplantation with high-dose chemotherapy and with or without total body irradiation. Treatment recommendations included using a wavelength of 650nm, power of 40mW, and each square centimetre treated with the required time to a tissue energy dose of 2 J/cm(2) (2s/ point)) (Migliorati 2013).

HPV Status An important clinical management consideration when aiding patients in preparation for radiotherapy is HPV (Human Papillomavirus) status. A new study evaluated HPV positive patients with oropharyngeal cancer and found that consideration of additional specific risk factors is required to optimize care (Vatca 2014). This retrospective analysis of 72 patients found that there was a 6.86-fold increase in the risk of having severe, grade 3-4 mucositis in HPV-positive patients. This effect was observed after adjusting for patient smoking status, nodal stage, radiotherapy technique, and radiotherapy maximum dose. Additionally, HPV status had significant effects on the objective weight loss during treatment and at three months following treatment. Non-smokers had a significant 2.70-fold increase in the risk of developing severe mucositis (Vatca 2014). This study highlights the need to take extra precaution and employ aggressive prophylactic measures in these patient populations.

Conclusion Naturopathic doctors are well equipped with a variety of natural interventions to help prevent and manage mucositis in patients with cancer undergoing chemo and/ or radiation therapy. These include the use of chamomile, licorice, DGL, glutamine, honey, and low level laser therapy. As is often the case, it is unlikely there will be one therapy that is suitable for treating all patients with oral mucositis. Using a multi-agent and sequenced approach tailored to each individual patient, while taking into consideration specific risk factors such as local radiation to the head or neck, chemotherapy agents known to cause high grades of mucositis, HPV-status, may be the most effective treatment approach at this time. Patients in these high risk categories should be treated more aggressively. Controversy around use of glutamine currently dictates that its use should be limited to patients undergoing active treatment. Further investigation of these safe, simple measures is needed.

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The Journal of IHP REFERENCES Braga, F., Santos, A., Bueno, P., et al. Use of Chamomilla recutita in the prevention and treatment of oral mucositis in patients undergoing hematopoietic stem cell transplantation: A Randomized Controlled, Phase II Clinical Trial. Cancer Nursing 2014 Sep 17. Cerchietti LC, Navigante AH, Lutteral MA, Castro MA, Kirchuk R, Bonomi M, Cabalar ME, Roth B, Negretti G, Sheinker B, Uchima P. Double-blinded, placebo-controlled trial on intravenous L-alanyl-L-glutamine in the incidence of oral mucositis following chemoradiotherapy in patients with headand-neck cancer. Int J Radiat Oncol Biol Phys. 2006 Aug 1;65(5):1330-7. Chen, J., Herrup, K. Glutamine acts as a neuroprotectant against DNA damage, beta-amayloid and H2O2-induced stress. PLoS one. 2012 7(3).

Oberoi, S et al. Effect of prophylactic low level laser therapy on oral mucositis: a systematic review and meta-analysis. PLoS one. 2014 Sep 8;9(9):e107418 Radiation Therapy Oncology Group. Acute radiation morbidity scoring criteria. 2014 Retrieved from http://www.rtog.org/ResearchAssociates/ AdverseEventReporting/AcuteRadiationMorbidityScoringCriteria.aspx Raeessi, M., Raeessi, N., Panahi, Y., et al. “Coffee plus Honey” versus “topical steroid” in the treatment of Chemotherapy-induced Oral Mucositis: a randomized controlled trial. BMC Complementary and Alternative Medicine. 2014. 14:2293. A

Curi, R., Lagranha, C., Doi, S., et al. Molecular Mechanisms of Glutamine Action. Journal of Cellular Physiology. 2005. 204:392-401.

Raeessi, M., Aslani, J., Raeessi, N., et al. Persistent post-infectious cough is better treated by which one? Prednisone, Honey, Coffee or Honey plus Coffee: a meta-analysis. Indian J Traditional Knowledge. 2014, 13(3):453460. B

Das, S., Agarwal, S., and Chandola, H. Protective effect of Yashtimadhu (Glycyrrhiza glabra) against side effects of radiation/chemotherapy in head and neck malignancies. Ayu. 2011. 32(2):196-199.

Raeessi, M., Aslani, J., Raeessi, N., et al. Honey plus Coffee versus systemic steroid in the treatment of persistent post-infectious cough: a randomized controlled trial. Prim Care Respir J 2013. 22(3):325-330.

Das, S., Das, V., Guati, A., et al. Deglycyrrhizinated liquorice in aphthous ulcers. Journal of the Association of Physicians of India. 1989. 47(10):647.

Raeessi, M. Aslani, J., Gharaie, H., et al. Honey with Coffee: a new finding in the treatment of Persistent Postinfectious Cough. Iran J Otorhinolaryngol. 2011 23(2):1-8.

Dehpour AR, Zolfaghari ME, Samadian T, Vahedi Y. The protective effect of liquorice components and their derivatives against gastric ulcer induced by aspirin in rats. J Pharm Pharmacol. 1994 Feb;46(2):148-9. Ghalayani P, Emami H, Pakravan F, Nasr Isfahani M. Comparison of triamcinolone acetonide mucoadhesive film with licorice mucoadhesive film on radiotherapy-induced oral mucositis: A randomized double-blinded clinical trial. Asia Pac J Clin Oncol. 2014 Oct 28. doi: 10.1111/ajco.12295. [Epub ahead of print] Gibson, R., Keefe, D., Lalla, R., et al. Systematic review of agents for the management of gastrointestinal mucositis in cancer patients. Supportive Care in Cancer. 2013. 21(1), 313-326. Keefe, D. M., Schubert, M. M., Elting, L.S., et al. Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer. 2007 109(5):820-831. Guarav, K., Goel, R., Shukla, M., et al. Glutamine: A novel approach to chemotherapy-induced toxicity. Indian J Med PAediatr Oncol. 2012 Jan 33(1):13-20. Martin, M., Sherman, J., van der Ven, P., et al. A controlled trial of a dissolving patch concerning glycyrrhiza (licorice) herbal extract for the treatment of aphthous ulcers. General Dentistry. 2008. 56(2):206-210. Migliorati, C., Hewson, I., Lalla, R., et al. Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients. Support Care Cancer 2013 Jan; 21 (1): 333-41. Mills, S., Bone, K. Principles and Practice of Phytotherapy. Edinburgh: Churchill Livingstone. 2000. 472. Morgan AG, McAdam WA, Pacsoo C, Darnborough A. Comparison between cimetidine and Caved-S in the treatment of gastric ulceration, and subsequent maintenance therapy. Gut. 1982 Jun;23(6):545-51. Noe, J.E. L-glutamine use in the treatment and prevention of mucositis and cachexia: a naturopathic perspective. Integrative Cancer Therapies. 2009. 8(4):409-415.

Savarese, D. M., Savy, G., Vahdat, L. Prevention of chemotherapy and radiation toxicity with glutamine. Cancer Treatment Reviews. 2003. 29(6):501-513. Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyh-Chang N, Kang Y, Fleming JB, Bardeesy N, Asara JM, Haigis MC, DePinho RA, Cantley LC, Kimmelman AC. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature. 2013 Apr 4;496(7443):101-5. Song, J., Twusmasi-Ankrah, P., & Salcido, R. Systematic review and meta-analysis on the use of honey to protect from the effects of radiation-induced oral mucositis. Advances in Skin and Wound Care. 2012. 25(1):23-28. Sonis, S., et al. Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity. Oral Oncol. 1998. 34:39-43. Stolpman, D., Benner, K., & Flora, K. A cautionary note regarding glycyrrhiza (licorice root). Am J Gastroenterol. 1999 Feb 94(2):540-541. Stubbe, C., Valero, M. Complementary Strategies for the Management of Radiation Therapy Side Effects. Journal of the Advanced Practitioner in Oncology. 2013;4:219-231. Vatca, M., Lucas, J., Laudadio J., et al. Retrospective analysis of the impact of HPV status and smoking on mucositis in patients with oropharyngeal squamous cell carcinoma treated with concurrent chemotherapy and radiotherapy. Oral Oncology 2014 Sep; 50(9):869-76. World Health Organization. WHO Handbook for reporting results of cancer treatment. Geneva: World Health Organization 1979. Worthington HV, Clarkson JE, Bryan G, Furness S, Glenny AM, Littlewood A, McCabe MG, Meyer S, Khalid T. Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2011 Apr 13;(4):CD000978.

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

Mechanism of melatonin in oncology the great multi-tasker Jessa Landmann, ND

Background Melatonin (chemically named N-acetyl-5-methoxytryptamine) is indeed a great multi-tasker. Whereas it is well known for its role in regulating circadian rhythm, much interest has been generated for its possible role in the pathogenesis and treatment of other disorders, namely cancer. The deviation from its primary role in the control of circadian rhythms including sleep came about from the observation that not only is it synthesized in the pineal gland, but also in the retina, GI tract, bone marrow and leukocytes (Hardeland 2011). Furthermore, in humans, melatonin receptors have been identified in enterocytes, gallbladder epithelium, exocrine and endocrine pancreatic cells, breast epithelium, ovarian granulosa cells, cardiac ventricular cells, and platelets, just to name a few (Fernando 2014, Hardeland 2011). Melatonin is secreted from the pineal gland in a diurnal rhythm, being higher at night in darkness than during the daylight hours. Another significant source of melatonin in the body is the gastrointestinal system, where gastrointestinal tract (GIT) cells synthesize melatonin to regulate digestive function (Bubenik 2008). Much research has been devoted to the oncological risk that night shift workers may experience due to the disruption of their circadian clock, and therefore disruption of melatonin secretion (Bracci 2013). It was proposed that this risk may be mediated by the loss of antioxidant and hormone modulating properties of melatonin. In addition to its antioxidant properties, melatonin also acts as an immune modulator, antiinflammatory, and possesses cytostatic as well as cytotoxic properties in vitro as well as in vivo. A PubMed search of “melatonin and cancer” reveals thousands of articles on the subject, and many excellent reviews have been published. This article will outline some of the mechanisms behind the powerful pleiotropic effects of melatonin, and how this translates clinically with respect to naturopathic oncology. The focus of this article will be elucidating melatonin’s mechanism of action, while clinical data can be found summarized elsewhere (Fritz 2009, Seely 2012, Wang 2012). December 2014 | www.ihpmagazine.com

Mechanisms Melatonin as antioxidant Several simultaneous processes act harmoniously to grant melatonin its impressive antioxidant abilities. First, it directly scavenges free radicals, both reactive oxygen species (ROS) and reactive nitrogen species (RNS). Hydrogen peroxide, while not a free radical but still an oxidizing agent, is also neutralized by melatonin. Interestingly, several melatonin metabolites produced during the scavenging reactions, such as N1-acetyl-N2-formyl-5methoxykynuramine (AFMK) and N1acetyl-5-methoxykynuramine (AMK) also have free radical scavenging abilities (Hardeland 2011). Melatonin indirectly acts an antioxidant by way of stimulating the production of glutathione, the most abundant intracellular antioxidant our cells possess. In one study, melatonin outperformed the hepatoprotective effects of the antioxidant N-acetylcysteine in rat models of methanol intoxication (Koksal 2012). In another study, a more dilute solution of melatonin was able to mimic the antioxidant effect of a much more concentrated vitamin C solution (Montilla-López 2002). In addition, 76

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melatonin up regulates the production of detoxifying enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase (SOD) (Reiter 2003). Oxidation leading to cell and DNA damage is a major contributor to oncogenesis, and melatonin may therefore be beneficial as a chemopreventive agent.

Melatonin as immune modulator Melatonin has immune enhancing effects on both the innate and adaptive immune system. Melatonin has been shown to increase the production of natural killer cells (NK), monocytes and leukocytes (Srinivasan 2008). NK cells are the primary innate immune cell responsible for killing cancer cells by releasing cytotoxic proteins such as perforin and granzyme (Lui 2012). Melatonin also enhances the production of IL-1, IL-6, TNF-α and IL-12 from monocytes, and enhances the production of IL-2, IFN-ψ and IL-6 from peripheral blood mononuclear cells (Srinivasan 2008). Together these cytokines activate and regulate the cytotoxic T cell response, which kill tumour cells. The immunosurveillance that the innate

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

Cytotoxicity refers to the ability of an agent to be toxic to cells, in other words, to klll them. Conventional therapies, such as chemotherapy, aim at being cytotoxic to cells. One such way an agent can be cytotoxic is by promoting apoptosis.

and adaptive immune system help provide may have more of a role in the prevention of tumours.

Melatonin as anti-inflammatory It is well accepted that over expression of COX-2 in tissues is important in mediating cancer growth and metastasis (Generali 2014, Khan 2011). Further, cancer cells themselves over express COX-2, leading to a self perpetuating system. Several studies have shown that melatonin possesses COX-2 suppressing actions at a pharmacological dose of 1mM (Wu 2014). Additionally, the previously mentioned metabolites of melatonin, AMFK and AMK, in addition to having antioxidant potential, also inhibit COX-2 expression (Wu 2014). Other immune cells involved in the inflammatory process, such as macrophages, have been shown to secrete melatonin, suggesting that melatonin is a key endogenous molecule released in response to inflammation (Wu 2014). Melatonin has also been shown to inhibit pro-inflammatory cytokines IL-8 and TNF-Îą in neutrophils, suggesting it may help to reduce the effects of acute and chronic inflammation (Silva 2004).

Melatonin as cytostatic Cytostasis refers to the inhibition of cellular growth and replication. There are numerous studies on the anti-proliferative effects of melatonin on various types of cancer cells both in vitro and in vivo, and a comprehensive review of these is beyond the scope of this article. However, one of the mechanisms suggested as responsible for such inhibition is activation of p21 and p53 tumour suppressor genes, which act by halting the cell cycle (Mediavilla 1999). A second

cytostatic mechanism may be via melatoninâ&#x20AC;&#x2122;s antiangiogenic effects. Melatonin appears to inhibit hypoxia inducible factor (HIF-1) and vascular endothelial growth factor (VEGF), both of which drive the growth of new blood vessels in the tumour environment (Lissoni 2001). Thirdly, melatonin may have antimetastatic effects via inhibition of matrix metalloproteinase-9 (MMP-9) activity, an enzyme associated with extracellular matrix remodelling and cancer metastasis (Rudra 2013). Melatonin also appears to increase expression of cell surface adhesion proteins, E-cadherin and beta1-integrin, which may decrease cancer cell migration and metastasis (Ortiz-Lopez 2009).

Melatonin as cytotoxic Cytotoxicity refers to the ability of an agent to be toxic to cells, in other words, to klll them. Conventional therapies, such as chemotherapy, aim at being cytotoxic to cells. One such way an agent can be cytotoxic is by promoting apoptosis. The studies on the apoptotic potential and mechanisms of melatonin are quite exciting, as studies are showing it has this ability in both hematological and solid tumour cell lines, such as breast cancer, colon cancer, hepatocarcinoma, glioma and neuroblastoma, lymphoma and leukemia (Bizzarri 2013). Studies have shown that Burkitt lymphoma cells, and both acute and myeloid leukaemia undergo apoptosis via activation of caspase-3, an increase in cytochrome c levels, and down regulation of the anti-apoptotic protein Bcl-2 (Trubiani 2005). Whereas not all studies in these cells lines confirm this exact mechanism, studies generally support the apoptotic effects of melatonin. In solid tumours, many interesting findings December 2014 | www.ihpmagazine.com

have been published. One study published evidence with respect to the apoptotic effect in breast cancer cell lines, showing that not only was p53 upregulated, but also its transcriptional agents, Bax, p21 and p27 (el-Aziz 2005). This effect was evident in both hormone dependent and hormone independent cancers. Studies in highly aggressive pancreatic cell lines show that melatonin had apoptotic effects via stimulation of caspase proteins (Gonzalez 2011, Leja-Szpak 2010). Melatonin exerted apoptotic effects in hormone sensitive and insensitive prostate cancer cells via inhibition of Sirt1, a gene over expressed in many cancers that when inhibited is associated with increased levels of apoptosis (Jung Hynes 2011). The same inhibition of Sirt1 was found in osteosarcoma cell lines (Cheng 2013). Sirt1 activity in cancer cells is associated with silenced tumour suppressor genes and cancer resistance to chemotherapy and ionizing radiation (Gonzalez 2011), and therefore inhibition of same may prove to be a target for gene therapy regimens.

Melatonin and Radiochemotherapy The basic tenet for the use of radiochemotherapy is that the ionizing radiation or drug will cause sufficient damage to kill cancer cells. However, this damage is extended to non-cancerous cells as well, resulting in often severe side effects. Recent studies have investigated the role of melatonin alongside radiochemotherapeutic regimens. Specifically, studies demonstrate that melatonin reproducibly decreases the toxic side effects of these treatments (Kucuktulu 2012, Mand 2009, Ortiz 2014, Seely 2012). Radioprotective agents are those that are given prior to radiotherapy to reduce injuries. Rat studies have shown that melatonin given after irradiation provides no radioprotective benefit (Shirazi 2007). It appears that melatonin may need to be administered beforehand to be present inside the cell prior to irradiation (Manda 2009). An ideal radioprotector should fulfill several criteria: 1) must provide significant protection against the effects of radiation; 2) must have a general protective effect on the majority of organs; 3) must have an acceptable route of administration, preferable orally or intramuscularly; 4) must have an acceptable toxicity profile; 5) must have an acceptable stability profile; and 6) must have compatibility with the wide range of other drugs that will be available to patients (Hosseinimehr 2007). Vijayalaxmi et al. conducted the first in vivo/in vitro studies showing that melatonin could be used as a cytoprotective agent for human cells exposed to ionizing radiation. In a study of healthy human volunteers, blood was taken before, one hour and two hours after a single dose of 300 mg of melatonin was given orally. Immediately after the blood was taken, it was exposed to 150 cGy of radiation and was cultured. The exposure of the cells to the radiation caused chromosomal aberrations, and lymphocytes collected after melatonin administration exhibited 60-65% reduced incidence of damage, with the best protective effect after two hours (Vijayalaxmi 2002). As the typical dose of melatonin is 20 mg per day, 300 mg seems at first to be quite high. However, the author showed that in humans, a dose of 1 78

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gram daily for 30 days resulted in no observable negative side effects (Vijayalaxmi 2004). A recent meta-analysis looked at the efficacy of adjuvant melatonin on response rates, survival and reduction of side effects related to radiochemotherapy (Wang 2012). The pooled data showed remission rates of 32.6% for the melatonin group versus 16.5% for the groups without melatonin. Similarly, survival rates were 52.2% for the melatonin group and 28.4% for the groups without melatonin. Studies that reported side effects showed overall rates markedly reduced when melatonin was used as an adjuvant with radiochemotherapy, including thrombocytopenia (2.2% versus 19.7%), neurotoxicity (2.5% versus 15.2%), and fatigue (17.2% versus 49.1%). Another recent meta-analysis of 19 studies compared the cancer response rates to melatonin plus a chemotherapeutic drug to chemotherapy without melatonin (Seely 2012). The overall result showed a significant benefit on complete response, partial response, and stable disease with the addition of melatonin. Pooled results from trials evaluating mortality showed that the addition of melatonin reduced mortality rates at one year, compared to patients who did not receive melatonin, relative risk (RR) 0.63, 95% confidence interval (CI) 0.53-0.74; p< .001 (Seely 2012). Regarding the results for the effect of adjuvant melatonin on toxicities associated with chemotherapy, positive outcomes were found for the reduction of asthenia, leucopenia, nausea and vomiting, hypotension and thrombocytopenia. Side effects not improved with the addition of melatonin included diarrhea, anemia and alopecia (Seely 2012). Dosages from the trials included in this meta analysis ranged from 10-40mg, with 20mg being most common, given at bedtime (Seely 2012).

Conclusion As briefly reviewed above, melatonin truly is a great multitasker. Its many actions include immune modulator, antioxidant, anti-inflammatory, anti-angiogenic, anti-metastatic, antiproliferative, and pro-apoptotic. In addition, it has the ability to modify gene expression, reduce side effects of radio chemotherapy, and improve response rates to radio chemotherapy. Whereas the molecular mechanisms reviewed in this article are by no means exhaustive, this article is meant to ignite a level of excitement about an impressive supplement for anyone interested in naturopathic oncology.

References

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Rudra DS, Pal U, Maiti NC, Reiter RJ, Swarnakar S. Melatonin inhibits matrix metalloproteinase-9 activity by binding to its active site. J Pineal Res. 2013 May;54(4):398-405

Hardeland R, Cardinali DP, Srinivasan V, Spence DW, Brown GM, PandiPerumal SR. Melatonin--a pleiotropic, orchestrating regulator molecule. Prog Neurobiol. 2011 Mar;93(3):350-84.

Seely D, Wu P, Fritz H, Kennedy DA, Tsui T, Seely AJ, Mills E. Melatonin as adjuvant cancer care with and without chemotherapy: a systematic review and meta-analysis of randomized trials. Integr Cancer Ther. 2012 Dec;11(4):293-303.

Hosseinimehr SJ. Foundation review: trends in the development of radioprotective agents. Drug Discovery Today, 2007; 12(19/20). Jung-Hynes B, Schmit TL, Reagan-Shaw SR, Siddiqui IA, Mukhtar H, Ahmad N. Melatonin, a novel Sirt1 inhibitor, imparts antiproliferative effects against prostate cancer in vitro in culture and in vivo in TRAMP model. J Pineal Res. 2011 Mar;50(2):140-9. Kucuktulu E. Protective effect of melatonin against radiation induced nephrotoxicity in rats. Asian Pac J Cancer Prev. 2012;13(8):4101-5. Khan Z, Khan N, Tiwari RP, Sah NK, Prasad GB, Bisen PS. Biology of Cox-2: an application in cancer therapeutics. Curr Drug Targets. 2011 Jun;12(7):1082-93. Koksal M, Kurcer Z, Erdogan D, Iraz M, Tas M, Eren MA, Aydogan T, Ulas T. Effect of melatonin and n-acetylcysteine on hepatic injury in rat induced by methanol intoxication: a comparative study. Eur Rev Med Pharmacol Sci. 2012 Apr;16(4):437-44. Leja-Szpak A, Jaworek J, Pierzchalski P, Reiter RJ. Melatonin induces proapoptotic signaling pathway in human pancreatic carcinoma cells (PANC-1). J Pineal Res. 2010 Oct;49(3):248-55. Lissoni P, Rovelli F, Malugani F, Bucovec R, Conti A, Maestroni GJ. Anti-angiogenic activity of melatonin in advanced cancer patients. Neuro Endocrinol Lett. 2001;22(1):45-7. Liu Y, Zeng G. Cancer and innate immune system interactions: translational potentials for cancer immunotherapy. J Immunother. 2012 May;35(4):299-308. Manda K, Ueno M, Anzai K. Cranial irradiation-induced inhibition of neurogenesis in hippocampal dentate gyrus of adult mice: attenuation by melatonin pretreatment. J Pineal Res. 2009 Jan;46(1):71-8. Mediavilla MD, Cos S, Sánchez-Barceló EJ. Melatonin increases p53 and p21WAF1 expression in MCF-7 human breast cancer cells in vitro. Life Sci. 1999;65(4):415-20.

Shirazi A, Ghobadi G, Ghazi-Khansari M. A radiobiological review on melatonin: a novel radioprotector. J Radiat Res. 2007 Jul;48(4):263-72. Silva SO, Rodrigues MR, Ximenes VF, Bueno-da-Silva AE, AmaranteMendes GP, Campa A. Neutrophils as a specific target for melatonin and kynuramines: effects on cytokine release. J Neuroimmunol. 2004 Nov;156(1-2):146-52. Srinivasan V, Spence DW, Pandi-Perumal SR, Trakht I, Cardinali DP. Therapeutic actions of melatonin in cancer: possible mechanisms. Integr Cancer Ther. 2008 Sep;7(3):189-203. Trubiani O, Recchioni R, Moroni F, Pizzicannella J, Caputi S, Di Primio R. Melatonin provokes cell death in human B-lymphoma cells by mitochondrial-dependent apoptotic pathway activation. J Pineal Res. 2005 Nov;39(4):425-31. Vijayalaxmi, Reiter RJ, Tan DX, Herman TS, Thomas CR Jr. Melatonin as a radioprotective agent: a review. Int J Radiat Oncol Biol Phys. 2004 Jul 1;59(3):639-53. Vijayalaxmi, Thomas CR Jr, Reiter RJ, Herman TS. Melatonin: from basic research to cancer treatment clinics. J Clin Oncol. 2002 May 15;20(10):2575-601. Wang YM, Jin BZ, Ai F, Duan CH, Lu YZ, Dong TF, Fu QL. The efficacy and safety of melatonin in concurrent chemotherapy or radiotherapy for solid tumors: a meta-analysis of randomized controlled trials. Cancer Chemother Pharmacol. 2012 May;69(5):1213-20. Wu KK, Cheng HH, Chang TC. 5-methoxyindole metabolites of L-tryptophan: control of COX-2 expression, inflammation and tumorigenesis. J Biomed Sci. 2014 Mar 3;21:17.

December 2014 | www.ihpmagazine.com

Questions 1. Melatonin is also known as: a) 5-hydroxytryptamine b) N-acetyl-5-methoxytryptamine c) N1-acetyl-5-methoxykynuramine d) None of the above

6. Melatonin promotes angioneogenesis via induction of HIF-1 and VEGF. a) True b) False

2. Which of the following is true about melatonin physiology? a) Melatonin is synthesized by the cells of the gastrointestinal tract. b) Melatonin receptors have been identified in ovarian granulosa cells, cardiac ventricular cells, breast epithelium, and the pancreas. c) The association between night shift work and elevated risk of cancer has been attributed to disruptions of melatonin secretion. d) All of the above 3. Melatonin has been shown to have antioxidant effects. Which of the following is NOT true about melatonin’s antioxidant effects? a) Melatonin scavenges reactive oxygen species (ROS) and reactive nitrogen species (RNS). b) Melatonin may not be as strong an antioxidant as N-aceytlcysteine or vitamin C. c) Melatonin upregulated glutathione reductase. d) Melatonin metabolites produced in ROS scavenging reactions may also have antioxidant activity. 4. Melatonin has been shown to upregulate NK cell production, but downregulates leukocytes and monocytes. a) True b) False

7. Melatonin decreases the expression of which of the following cell surface proteins. a) E-cadherin b) Alpha-1 integrin c) F-actin d) Matrix metalloproteinase-9 8. Evidence from breast cancer cell lines shows that melatonin has proapoptoic effects via upregulation of p53 and its transcriptional agents, Bax, p21 and p27. a) True b) False 9. As a radioprotective and radiosensitizing agent, melatonin seems best administered following radiation therapy. a) True b) False 10. Evidence from meta-analyses shows that use of adjunctive melatonin decreases incidence of specific chemotherapy side effects. These include which of the following? a) Leucopenia, b) Nausea and vomiting, c) Thrombocytopenia d) All of the above

5. Which of the following is true about melatonin’s effect on inflammation? a) Melatonin suppresses COX-2. b) Melatonin is produced by immune cells involved in the inflammatory process such as dendrites. c) Melatonin increases cytokines IL-8 and TNF, suggesting it can strengthens anti-inflammatory signaling. d) All of the above.

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GREENS+ ORIGINAL Greens + by Genuine Health is a nourishing superfood blend containing 23 plant-based ingredients such as lecithin, spirulina, barley grass, wheat grass, chlorella, eight strains of probiotics, and herbs such as Siberian ginseng and milk thistle to help support key areas such as stress management and liver function. As such, Greens+ is an ideal product for improving energy and vitality, balance pH, and providing antioxidants to support good health. Greens+ formula has been the subject of extensive research, investigating its effect on a variety of endpoints including in vivo antioxidant capacity, pH and alkalinity, energy, osteoporosis, and cancer cell growth (Boon 2004, Rao 2008, Rao 2011). Research at the University of Toronto has shown that greens+ demonstrates potent antioxidant and cell protective effects in vitro and in vivo (Guthrie 2011, International Journal of Molecular Science, Rao 2011). The greens+ formula was found to contain key phytonutrients such as quercetin, apigenin, kaempferol, and luteolin. The formula was able to inhibit lipid peroxidation, which may present a role in chronic diseases including cardiovascular, neurological, and psychiatric illness. In a human clinical trial, subjects supplemented with greens+ for one month experienced significant increases in their in vivo antioxidant capacity, a reduction in oxidative cellular damage to fats and proteins, and an increase in the key antioxidant enzyme, glutathione peroxidase (Rao 2011). This study underscores the bioavailability of nutrients in this formula as well as its therapeutic effect in the human body. Interestingly, the ingredient lecithin may account for up to 12-15% of the total antioxidant capacity of the greens+ formula. A randomized, double blind, placebo controlled trial conducted in over 100 subjects at the University of Toronto found that supplementation with greens+ was effective in increasing energy and vitality, with significant improvements compared to placebo (p=0.018) (Boon 2004). There were also trends toward improved mental health, well-being and overall health associated with use of greens+. The greens+ formula has been demonstrated to influence bone metabolism (Rao 2008). In an in vitro study, exposure of osteoblast-like cells, SaOS-2 cells, to various concentrations of total free polyphenolic from greens+ extracts resulted in increased osteoblast number, and stimulated mineralized bone nodule formation (Rao 2008). These results indicate that greens+ may promote maturation of osetoprogenitors and exert beneficial effects on bone formation. Authors states, “we speculate that it may be a good alternative to drugs for the prevention of osteoporosis” (Rao 2008). A second mechanism of its effect on bone is modulation of the Potential Renal Acid Load (PRAL); PRAL analysis evaluates an agent’s potential for promoting acid or alkaline formation in vivo. In general, foods such as fruits and vegetables are alkaline forming, while meats and grains are acid forming. With chronic over-consumption of “acidic” foods, calcium is released from bone to buffer the acid produced (Remer 2011, Shi 2012) . Greens+ has been shown to promote an alkaline state, and may offsetting the negative effects of meat and grain consumption by reducing calcium release and helping preserve bone mass. Greens+ Formula Ingredients per 8.5g Dose Lecithin (97% oil free; soybean; 26% 2171 phosphatidylcholine) Spirulina platensis (Spirulina cells) 1450 Malus domestica (Apple fruit) 1033 Hordeum vulgare (Organic barley grass) 734 Medicago sativa (Organic alfalfa grass) 383 Triticum aestivum (Organic wheat grass) 383 Chlorella pyrenoidosa (Japanese 383 chlorella) Glycine max (Organic soy sprouts) 383 Oryza sativa (Organic whole brown rice 383 kernel) Royal jelly standardized to 5% 10-HAD 150 Bee pollen 150 Glycyrrhiza uralensis (Licorice roots 116 standardized to 10% glycyrrhizin (5:1 = 580mg) Malpighia glabra (Acerola berry juice 115 standardized to 18% vitamin C) FOS (fructooligossacharides) (from 100 chicory root; [Cichorium intybus]) Eight bacterial cultures 100 Lactobacillus helveticus (R0052) 0.19 Lactobacillus rhamnosus (R0011) 0.43 Lactobacillus casei (R0215) 0.09 Lactobacillus plantarum (R1012) 0.09 Lactobacillus salivarius (R0078) 0.04 Bifidobacterium longum (R0175) 0.04 Bifidobacterium bifidum (R0071) 0.04 Bifidobacterium breve (R0070) 0.24 Eleutherococcus senticosus (Siberian 60 ginseng roote extract standardized to 0.8% eleutherosides (28:1 = 1680mg)) Silybum marianum L. (Milk thistle seed 60 extract standardized to 86% silymarin (40:1 = 2400mg)) Beta vulgaris (Organic red beet root) 43 Palmaria palmate (Atlantic dulse 33 seaweed) Ginkgo biloba L. leaf extract 20 standardized to 24% ginkgo flavonglycosides and 6% terpene lactones (50:1 = 1000mg) Camellia sinensis L. (Japanese green tea 15 leaf extract standardized to 90% polyphenols (20:1 = 300mg)) Vaccinium myrtillus L. (European 10 bilberry extract standardized to 25% anthocyanidins (100:1 = 1000mg)) Vitis vinifera (Grape extract standardized 5 to 95% proanthocyanidins and 200 ppm resveratrol (500:1 = 2500mg)) Non medicinal ingredients: stevia, skim milk

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

gm mg mg

Finally, greens+ also contains eight strains of Lactobacillus and Bifidobacertium probiotic species to ensure healthy digestion and immune function. These species have been shown to improve irritable bowel syndrome, reduce upper respiratory tract infections, and may have a role in maintaining healthy immune tolerance (Rerksuppaphol 2012, Yoon 2014). Greens+ is one of the most thoroughly research nutraceutical blends of its kind, with confirmed benefits on several important areas of health demonstrated by laboratory studies and human clinical research. Recommended use: To increase your energy and well-being. Adult dosage: Mix 3 tsp (8.5g) in 1 cup (250mL) of pure water or juice. Shake well. If you are a new user of greens+, begin with 1 tsp daily and gradually increase to 3 tsp daily over a 3 week period. Do not take on empty stomach. Consult a health care practitioner for use beyond 3 months. Caution: Not to be taken by children, during pregnancy, while breastfeeding, by those on medication or with chronic health problems unless under the recommendation of a health care practitioner. Consult a health care practitioner prior to use if you have nausea, fever, vomiting, bloody diarrhea or severe abdominal pain. Do not use if you have gastrointestinal blockage or an immune-compromised condition (e.g. AIDS, lymphoma, patients undergoing long-term corticosteroid treatment). Discontinue use and consult a health care practitioner if symptoms of digestive upset occur, persist or worsen beyond 3 days. Use with caution if allergic to bee products. Keep refrigerated after opening. References Boon H, Clitheroe J, Forte T. Effects of greens+: a randomized, controlled trial. Can J Diet Pract Res. 2004 Summer;65(2):66-71. Rao LG, Balachandran B, Rao AV. Polyphenol extract of Greens+™ nutritional supplement stimulates bone formation in cultures of human osteoblast-like SaOS-2 cells. J Diet Suppl. 2008;5(3):264-82. Rao V, Balachandran B, Shen H, Logan A, Rao L. In vitro and in vivo antioxidant properties of the plant-based supplement greens+™. Int J Mol Sci. 2011;12(8):4896-908. Remer T, Manz F, Alexy U, Schoenau E, Wudy SA, Shi L. Long-term high urinary potential renal acid load and low nitrogen excretion predict reduced diaphyseal bone mass and bone size in children. J Clin Endocrinol Metab. 2011 Sep;96(9):2861-8. Rerksuppaphol S, Rerksuppaphol L. Randomized controlled trial of probiotics to reduce common cold in schoolchildren. Pediatr Int. 2012 Oct;54(5):682-7. Shi L, Libuda L, Schönau E, Frassetto L, Remer T. Long term higher urinary calcium excretion within the normal physiologic range predicts impaired bone status of the proximal radius in healthy children with higher potential renal acid load. Bone. 2012 May;50(5):1026-31. Vaghef-Mehrabany E, Alipour B, Homayouni-Rad A, Sharif SK, Asghari-Jafarabadi M, Zavvari S. Probiotic supplementation improves inflammatory status in patients with rheumatoid arthritis. Nutrition. 2014 Apr;30(4):430-5. Yoon JS, Sohn W, Lee OY, Lee SP, Lee KN, Jun DW, Lee HL, Yoon BC, Choi HS, Chung WS, Seo JG. Effect of multispecies probiotics on irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Gastroenterol Hepatol. 2014 Jan;29(1):52-9.

Ascorbates SAP PRODUCT MONOGRAPH

VITAMIN C AND IMMUNE FUNCTION

SELENIUM ASCORBATE

Vitamin C deficiency can contribute to reduced resistance against pathogens, while an increased supply enhances many immune system parameters.[5] Vitamin C is highly concentrated in the adrenal gland, and acts as an antioxidant [6] to reduce free radicals and reactive oxygen species.

ASCORBYL PALMITATE

Vitamin C (ascorbic acid) is a water-soluble vitamin which is required in the body to form collagen in bones, cartilage, muscle and blood vessels, and aids in the absorption of iron. Although the human body cannot assemble vitamin C de novo, it is capable of conserving it once obtained in the diet.

Increased levels of vitamin C have been associated with a reduced risk of colon cancer.[7] Oral supplementation of vitamin C has been showed to restore immune function abnormalities following toxic chemical exposure. In a study by Heuser & Vojdani (1997), application of oral granulated buffered vitamin C in water at a dosage of 60 mg/kg body weight resulted in a ten-fold enhancement of NK activity in 78% of patients, and restoration of lymphocyte blastogenic responses to T- and B-cell mitogens to normal levels.[8] Vitamin C administration may also increase killer T-cell activity, which may have implications in mitigating early stages of tumor development.[9]

ENHANCED BIOAVAILABILITY

Bioavailability refers to the degree to which a nutrient (or drug) becomes available to the target tissue after it has been administered.

Vitamin C is released upon the presence of adrenocorticotropic hormone.[4] A study of 12 males (6 smokers and 6 nonsmokers) found the bioavailability of synthetic ascorbic acid (powder administered in water) to be superior to that of orange juice, based on blood levels of ascorbic acid, and not different based on ascorbic acid in white blood cells.[10]

CITRUS BIOFLAVONOIDS

Some studies have shown that ascorbic acid in citrus extract is more available than synthetic ascorbic acid alone.[11] Bioflavonoids are a class of water-soluble plant pigments. In one study, the synthetic ascorbic acid given in a natural citrus extract containing bioflavonoids (in the ratio of bioflavonoids to ascorbic acid of 4:1), proteins, and carbohydrates, was more slowly absorbed and 35% more bioavailable than synthetic ascorbic acid alone, based on plasma levels of ascorbate over time and 24-hour urinary excretion of ascorbate.[12]

CALCIUM ASCORBATE

White blood cells or leukocytes are cells of the immune system which defend the body against both infectious disease and foreign materials.[1]

Supplementation with calcium ascorbate has been shown to increase calcium ascorbate concentrations within leukocytes themelves. In a double-blind, placebo-controlled, four-way crossover study over 24 hours, supplementation of calcium ascorbate combined with metabolites resulted in superior vitamin C concentration in leukocytes versus vitamin C alone.[2]

MAGNESIUM ASCORBATE

Magnesium is important for bone and fatty acid formation, cell generation, activating B vitamins, as well as helping with the formation of ATP. Magnesium and ascorbic acid together improve the flexibility of blood vessels,[3] which plays a role in the functioning of a healthy heart.

ZINC ASCORBATE

Zinc is an essential trace element for all organisms. In human subjects, body growth and development is strictly dependent on zinc and the nervous, reproductive and immune systems are particularly affected by zinc deficiency.[13] Zinc has antioxidant properties, which protect against premature aging of the skin and muscles of the body.[14] It also helps speeding up the healing process after an injury. Zinc deficiency depresses immunity of humans.[15] Combined, zinc and ascorbic acid ameliorate levels of immunity which are needed to be productive on a day-to-day basis.

POTASSIUM ASCORBATE

Potassium, along with lifestyle changes, can be used to treat hypertension.[16] Similarly, ascorbic acid may have therapeutic effects on oxidative stress-induced diseases which encompass cardiovascular diseases, hypertension, chronic inflammatory diseases and diabetes.[17]

MANGANESE ASCORBATE

Manganese superoxide dismutase is the principal antioxidant enzyme in the mitochondria. Because mitochondria consume over 90% of the oxygen used by cells, they are especially vulnerable to oxidative stress. Manganese plays an important role in the metabolism of amino acids, carbohydrates and cholesterol.[18] Deficiency of manganese results in abnormal skeletal development. Manganese contributes to the synthesis of cartilage and bone.[19]

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In a study by Bertinato et al. (2007), selenium was found to have a sparing effect on vitamin C and alpha-tocopherol. Dietary restriction of selenium and ascorbic acid, both independently and in combination, resulted in significant (P < 0.05) decreased tissue alpha-tocopherol levels. Selenium restriction alone also resulted in decreased tissue ascorbic acid levels.[20] Ascorbyl palmitate is an amphipathic molecule, which means that one end is water-soluble and the other end is fat-soluble. When incorporated into the cell membranes of human red blood cells, ascorbyl palmitate has been found to protect them from oxidative damage.[21]

CLINICAL APPLICATIONS IN IMMUNOLOGY Vitamin C Deficiency - Scurvy

Although scurvy is uncommon, it may occur in certain malnourished individuals, those with increased vitamin C requirements (such as pregnant or breast-feeding women), or in infants whose only source of nourishment is breast milk.[22]

Vitamin C and the Common Cold

The prophylactic intake of vitamin C may reduce the duration of the illness in healthy persons. Supplementation of vitamin C is most effective in cases of physical strain or insufficient intake of the vitamin. Antioxidant activity is also derived from other phytochemicals, mainly flavonoids.[5] Based on standardized clinical assessment, elderly patients who received 200 mg of vitamin C daily fared better than patients receiving placebo.[23]

Vitamin C and Allergies

Oral dosages of vitamin C significantly reduced bronchial responsiveness to inhaled histamine in patients with allergies.[9]

Ability to Reduce Harmful Effects of Smoking

In a study done to measure concentrations of blood vitamins A, C and E as well as coenzyme Q10 in smokers, it was found that they had significantly lower vitamin C levels. These could be normalized by supplementing with vitamin C. A lack of vitamin C may increase the risk of asthma.[24]

Iron Absorption Enhancement with Vitamin C

Vitamin C improves the oral absorption of iron. Concurrent vitamin C may aid in the absorption of iron dietary supplements. Molecular cloning of mammalian duodenal brush-border reductase activity and studies in animals and man strongly supported ascorbate as the intracellular electron donor for duodenal ferrireductase activity and provided molecular mechanism for an intracellular role of ascorbate in intestinal iron absorption.[25]

Vitamin C Reduces Risk of Gallbladder Disease

Epidemiological investigation has indicated an independent association between serum ascorbic acid and a significantly lower prevalence of clinical gallbladder disease and asymptomatic gallstones. Ascorbic acid deficiency reduces the activity of hepatic cholesterol to bile acids and the risk of gallbladder disease.[9] References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25.

LaFleur Brooks, M. and D. LaFleur Brooks. Exploring Medical Language: A Student-Directed Approach 7th Edition, St. Louis, Missouri, USA: Mosby Elsevier, p. 398. Moyad, M.A., et al. “Vitamin C metabolites, independent of smoking status, significantly enhance leukocyte, but not plasma ascorbate concentrations”. Advanced Therapy Vol. 25, No. 10 (2008): 995–1009. Laurant, P., et al. “Dietary magnesium intake can affect mechanical properties of rat carotid artery”. British Journal of Nutrition Vol. 84, No. 7 (2000): 757–764. Padayatty, S., et al. “Human adrenal glands secrete vitamin C in response to adrenocorticotrophic hormone”. The American Journal of Clinical Nutrition Vol. 86, No. 1 (2007): 145–149. Ströhle, A. and A. Hahn. “[Vitamin C and immune function]”. Medizinische Monatsschrift für Pharmazeuten Vol. 32, No. 2 (2009): 49–54. Mitani, F., et al. “Ascorbate stimulates monooxygenase-dependent steroidogenesis in adrenal zona glomerulosa”. Biochemistry and Biophysical Research Communications Vol. 338, No. 1 (2005): 438–490. Johnston, C. Present Knowledge in Nutrition, 9th Edition, Vol. 1. International Life Sciences Institute, Washington, DC, 2007: 708. Heuser, G. and A. Vojdani. “Enhancement of natural killer cell activity and T and B cell function by buffered vitamin C in patients exposed to toxic chemicals: the role of protein kinase-C”. Immunopharmacology and Immunotoxicology Vol. 19, No. 3 (1997): 291–312. Johnston, C. Present Knowledge in Nutrition: 236–237. Pelletier, O. and M.O. Keith. “Bioavailability of synthetic and natural ascorbic acid”. Journal of the American Dietetic Association Vol. 64, No. 3 (1974): 271–275. Martí, N., et al. “Vitamin C and the role of citrus juices as functional food”. Natural Product Communications Vol. 4, No. 5 (2009): 677–700. Hidgon, J. and V. Drake. An evidence-based approach to vitamins and minerals: Health benefits and intake recommendations. New York: Thieme, 2003: p. 65 Rink, L. and P. Gabriel. “Zinc and the immune system”. The Proceedings of the Nutrition Society Vol. 59, No. 4 (2000): 541–552. Milbury, P.E. and A.C. Richer. Understanding the antioxidant controversy: Scrutinizing the “fountain of Youth”. Westport, CT, USA: Greenwood Publishing Group, 2008, p. 99. Ibs, K.H. and L. Rink. “Zinc-altered immune function”. The Journal of Nutrition Vol. 133, No. 5 Suppl. 1 (2003): 1452S–1456S. Vij, R. and A.J. Peixoto. “Management of nocturnal hypertension”. Expert Review of Cardiovascular Therapy Vol. 7, No. 6 (2009): 607–618. Tak, P.P., et al. “Rheumatoid arthritis and p53: how oxidative stress might alter the course of inflammatory diseases”. Immunology Today Vol. 21, No. 2 (2000): 78–82. Leach, R.M. and E.D. Harris. “Manganese,” in Handbook of nutritionally essential minerals elements, ed. R.A.S. O’Dell. New York, NY, USA: Marcel Dekker, Inc., 1997: p. 335–355. Keen, C.L. and S. Zidenberg-Cherr. “Manganese,” in Present Knowledge in Nutrition, eds. E.E. Ziegler and C.J. Filer. Washington, DC, USA: ILSI Press, 1996, p. 334–343. Bertinato, J., et al. “Sparing effects of selenium and ascorbic acid on vitamin C and E in guinea pig tissues”. Nutrition Journal Vol. 6, Issue 7 (2007): 1–9. Ross, D., et al. “Ascorbate 6-palmitate protects human erythrocytes from oxidative damage”. Free Radical Biology and Medicine Vol. 26, No. 1–2 (1999): 81–89. MedlinePlus. Scurvy. Updated 16 May 2014 • http://www.nlm.nih.gov/medlineplus/ency/article/000355.htm Barrett, B., et al. “Clinical significance of common cold treatment: professionals’ opinions”. WMJ 106, No. 8 (2007): 473–480. Song, S.M., et al. “[Concentrations of blood vitamin A, C, E, coenzyme Q10 and urine cotinine related to cigarette smoking exposure.” The Korean Journal of Laboratory Medicine Vol. 29, No. 1 (2009): 10–16. Atanassova, B.D. and K.N. Tzatchev. “Ascorbic acid—important for iron metabolism”. Folia Medica Vol. 50, No. 4 (2008): 11–16.

2014-12-09 3:35:23 PM

Nutritional Fundamentals for Health Inc.

Focus on Immunity Ascorbates SAP is a combination of vitamin C and bioflavonoids. Vitamin C has demonstrated the ability to reduce the duration and severity of the common cold. Citrus bioflavonoids inhibit the synthesis of different proinflammatory mediators including arachidonic acid derivatives, prostaglandins E2 and F2, thromboxane A2, and histamine release from mast cell. Please see product monograph on opposite page. Astragalus SAP contains 500 mg of astragalus. Astragalus polysaccharides have been shown to stimulate the pituitaryadrenal cortical activity and restore depleted red blood-cell formation in bone marrow. Astragalus may also restore T-cell counts to relatively normal ranges in suppressed patients. Berberine SAP contains 300 mg of berberine and 150 mg of goldenseal. Berberine has been used for its antimicrobial activity and is active against a wide range of organisms including bacteria, viruses, fungi, helminthes, and chlamydia. Vitamin D3 SAP comes as either a liquid or capsule format at a dosage of 1,000 IU. Vitamin D is a vitamin critical to human health. Insufficiency in serum hydroxyvitamin D levels may contribute to a host of disease processes including cardiovascular disease, cancer, autoimmune disease, and infections.

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 Please visit our website nfh.ca to view our full line of products

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SUPERFOOD. OPTIMIZE YOUR NUTRITION with Canada’s #1 research-proven superfood. Healthy diets don't always provide enough daily nutrients. Give your body everything it needs to support your optimal health with one serving of greens+ every day.

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