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s we put another successful and prosperous year behind us we are looking forward to serving you in 2014. I want to thank our staff, suppliers and our writers for their support; without you IHP would not have been a success. We are deeply touched every time we hear from our readers on how much they enjoy reading the journal and its impact on their practice! A big thank you goes out to Dr. Philip Rouchotas who has taken the vision of IHP and transformed into a very respected journal; it is very rare you get to work with an individual who is excited about every cover story! Every article! Thank you Philip for all your hard work… We would love your feed back on how we can better serve you. We look forward to seeing more of you in 2014! Happy Holidays & and Happy New Year from the staff at IHP and Nature’s Source!

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The US Centers for Disease Control report that a full 90% of all illness and disease is related to stress. Stress and the telomere connection A research team from Umeå University in Sweden has discovered that chronic stress shortens telomeres (Wikgren et al 2011). They note moreover that cortisol levels indicative of chronic stress are also associated with recurring depression and that chronically depressed people, as expected, have shorter telomeres. Meanwhile, fruit flies given Rhodiola rosea live an average of 10 percent longer than flies fed the usual nutritional fare, according to a University of California, Irvine study (Jafari et al 2007).

Stress and the immune connection Scientists have found a mechanism whereby chronic stress undermines immune function. Miller and colleagues reveal that chronic stress alters gene expression in monocytes, making the immune cells less responsive to the anti-inflammatory effects of cortisol and hyper-responsive to the proinflammatory cytokine NF-κB. The altered monocyte function thus creates a persistent proinflammatory state, a known risk factor for chronic disease. Miller comments to ScienceDaily news that those who care for chronically ill family members have white blood cells that “are not able to ‘receive’ the signal from cortisol that tells them to shut down inflammation.” (Elsevier 2008)

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References: Elsevier (2008, August 27). “Chronic Stress Alters Our Genetic Immune Response.” ScienceDaily. Retrieved January 6, 2012, from http://www.sciencedaily.com/releases/2008/08 /080827100816.htm (source, Miller G et al. Biological Psychiatry 2008; 64 (4): 266 DOI: 10.1016/j.biopsych.2008.03.017) Jafari M, et al. Rejuvenation Research 2007; 10(4): 587–602. doi: 10.1089/rej.2007.0560. Panossian A, Wagner H. Phytother Res. 2005 Oct;19(10):819–38.

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contents

This Issue: November/December 2013 • Vol. 6 • No. 6

30 Dr Andrew Wojcicki, MD Cover Story

The Vivian Medical Spa

Clinic Profile

38 The Community Clinic Roncesvalles

Successfully providing equal access to care

44 The Journal of IHP

Peer-reviewed articles on clinically revelant topics

Coming Next Issue ➜ Comprehensive management of hypertension ➜ Neurodegeneration in MS - strategies for intervention ➜ Bioidentical hormones in clinical practice Cover Photograph by Samantha Noakes

8 www.ihpmagazine.com l November / December 2013

Departments

4 Publisher’s Letter 11 Research News 19 Industry News 24 Calendar 27 Product Profiles 45 Editor’s Letter 49 Peer Review Board 53 Editorial Board 72 Continuing Education: The Metabolic Fate of Alpha Linolenic Acid By Leah Gillingham, MSc, PhD

How Does Nitric Oxide Reduce Cold & Flu Symptoms?

AORâ&#x20AC;&#x2122;s ColdNOx combines Andrographis + NO for a powerful weapon against URTIs. Andrographis paniculata has strong clinical data showing that it helps reduce the frequency, severity and duration of upper respiratory tract infections (URTIs) ranging from the common cold to pneumonia. Andrographis can produce noticeable improvements in symptoms like fatigue, sleeplessness, sore throat, nasal secretions, earaches, phlegm, cough and headaches in just 2-4 days. Nitric Oxide (NO) maximizes the delivery of immune factors, oxygen and nutrients to the site of infection by increasing blood flow, which speeds up the rate of recovery. NO is also a natural antimicrobial, killing pathogenic bacteria and viruses and helping to prevent infection.

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AOR ColdNOx – Product Monograph General Overview ColdNOx is essential during cold and flu season for those who have a weakened immune system and are prone to falling ill. ColdNOx contains Andrographis paniculata extract in combination with a supplemental source of nitric oxide (NO), potassium nitrate. This formula is the WORLD’S FIRST Andrographis paniculata enhanced with a natural source of supplemental nitric oxide. This novel formula reduces the frequency, severity and duration of upper respiratory tract infections. NO acts as a natural antimicrobial and increases circulation to support recovery. Green tea extract and citric acid are also included in AOR’s proprietary NOx3,2,1 Technology blend as synergistic agents to improve the body’s conversion of nitrate to NO and to enhance its effectiveness. Ingredients: Andrographis paniculata Extract Andrographis paniculata is a plant found primarily in Asia and India. In Traditional Chinese Medicine, it is used to remove heat, counteract toxicity and reduce swelling. In Ayurvedic and Thai medicine, it is used to treat fever associated with infectious diseases, and Scandinavians have used it as a cold and flu remedy. Andrographis has been shown to reduce the frequency of upper respiratory tract infections (URTIs) as well as the duration and severity of URTI symptoms of the common cold and sinusitis, bronchitis, pharyngotonsillitis and pneumonia in just 2-4 days. Such symptoms include tiredness, sleeplessness, sore throat, nasal secretions, earaches, phlegm, coughing and headaches. There is also preliminary evidence of a preventive effect. Adverse events were mild and infrequent. Collectively, the data from seven double-blind controlled trials suggest that A. paniculata is superior to a placebo in alleviating the subjective symptoms of uncomplicated URTIs (Coon, JT, 2004; Saxena RC et al., 2010). In a study of uncomplicated respiratory disease in 39 children between the ages of 4 and 11 years, A. paniculata significantly decreased the amount of nasal secretion and nasal congestion. It also accelerated the recovery time, whereas another herbal preparation containing Echinacea extract did not show the same efficacy. The treatment was well tolerated and the use of standard medication was significantly less in the group using Andrographis versus the groups using the other herbal brand or any other standard medication (Spasov AA, 2004). In another study in 107 school children, a randomized, placebo controlled, double-blind investigation evaluated a standardized extract of A. paniculata in the prophylaxis of the common cold during the winter season. The children received either 200 mg of the extract or a placebo daily for 3 months and were evaluated each week by a physician. During the first two months of treatment, there was no difference between the two groups. However, in the third month of treatment, there was significant difference in the occurrence of the common cold in the treated group (30%) when compared to the placebo group (62%). A study of a treatment group consisting of 95 individuals involved taking an herbal preparation containing A. paniculata for 5 days. The results of this study also showed that A. paniculata has a positive effect in the treatment of acute URTIs and helps relieve the inflammatory symptoms of sinusitis (Gabrielianm ES et al., 2002). One hundred and fifty-two adult patients with pharyngotonsillitis were enrolled in a randomized double blind study to assess the efficacy of Andrographis paniculata. The patients were randomized to receive either paracetamol or 3 g/day of Andrographis paniculata or 6 g/day of Andrographis paniculata for 7 days. The efficacy of paracetamol or high dose Andrographis paniculata was significantly more than that of low dose Andrographis paniculata at day 3 in terms of the relief of fever and sore throat. The clinical effects were not different at day 7 (Thamlikitkul V, 1991). Andrographis is thought to inhibit the growth of certain pathogens and inhibit access to cells by microbes and the toxins they produce. Studies have also found that Andrographis can reduce the symptoms and severity of colon issues such as acute diarrhea, bacillary dysentery (bacterial infection of the gut mucosa with blood in the stool) and urinary tract infections (Melchior J, 1997). Nitric Oxide Nitric oxide (NO) is produced in the body from consumed nitrates and nitrites and is thought to be responsible for many of the health benefits of a “Mediterranean diet.” NO acts as an anti-microbial and improves blood flow, bringing immune factors to the site of infection to speed up recovery. NO is a natural antimicrobial, helping to kill pathogenic bacteria and viruses, prevent infection and clear infections. NO is advocated for use in improving symptoms of respiratory difficulties. Acting as a physiological messenger, NO is becoming increasingly known as an important regulator in the nervous, immune and cardiovascular systems (Bredt, DS and Snyder SH, 1994). Clinical Indications: SUPPLEMENT FACTS: Serving Size: 1 Capsule Andrographis paniculata extract (33% andrographolides)

300 mg

Safety: The ingredients in this product have been extensively tested in human clinical trials and have been proven safe and effective at the recommended dosage. Cautions: Consult a health care practitioner prior to use if you are taking immunosuppressant, anticoagulant, antiplatelet, hypotensive, erectile dysfunction or nitrate-containing medications (or supplements). Do not use if you are allergic to plants of the Acanthaceae family. Some people may experience gastric discomfort, vomiting and/or loss of appetite. Consult a health care practitioner if symptoms persist or worsen or for use beyond 7 days. Pregnancy/Nursing: Do not use Adult Dosage: Take 1 capsule twice daily, or as directed by a qualified health care practitioner. References: D S Bredt and S H Snyder. Nitric Oxide: A Physiologic Messenger Molecule. Annual Review of Biochemistry. Vol. 63: 175-195 (Volume publication date July 1994). Cáceres DD, Hancke JL, Burgos RA, Sandberg F, Wikman GK. Use of visual analogue scale measurements (VAS) to assess the effectiveness of standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of common cold. A randomized double blind-placebo study. Phytomedicine. 1999 Oct;6(4):217-23. Coon JT and Ernst E. Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy. Planta Med. 2004 Apr;70(4):293-8. Gabrielian ES, Shukarian AK, Goukasova GI, Chandanian GL, Panossian AG, Wikman G, Wagner H. A double blind, placebo-controlled study of Andrographis paniculata fixed combination Kan Jang in the treatment of acute upper respiratory tract infections including sinusitis. Phytomedicine. 2002 Oct;9(7):589-97. Melchior J, Palm S, Wikman G. Controlled clinical study of standardized Andrographis paniculata extract in common cold-a pilot trial. Phytomedicine. 19961997;3:315-318. Saxena RC, Singh R, Kumar P, Yadav SC, Negi MP, Saxena VS, Joshua AJ, Vijayabalaji V, Goudar KS, Venkateshwarlu K, Amit A. A randomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata (KalmCold) in patients with uncomplicated upper respiratory tract infection. Phytomedicine. 2010 Mar;17(3-4):178-85. Spasov AA, Ostrovskij OV, Chernikov MV, Wikman G. Comparative controlled study of Andrographis paniculata fixed combination, Kan Jang and an Echinacea preparation as adjuvant, in the treatment of uncomplicated respiratory disease in children. Phytother Res. 2004 Jan;18(1):47-53. Thamlikitkul V, Dechatiwongse T, Theerapong S, Chantrakul C, Boonroj P, Punkrut W, Ekpalakorn W, Boontaeng N, Taechaiya S, Petcharoen S, et al. Efficacy of Andrographis paniculata, Nees for pharyngotonsillitis in adults. J Med Assoc Thai. 1991 Oct;74(10):437-42.

research news Gonadal steroids and body composition, strength, and sexual function in men

Complications following surgery for lumbar stenosis in veterans

This study provided 198 healthy men 20 to 50 years of age with goserelin acetate (to suppress endogenous testosterone and estradiol) and randomly assigned them to receive a placebo gel or 1.25g, 2.5g, 5g, or 10g of testosterone gel daily for 16 weeks. Another 202 healthy men received goserelin acetate, placebo gel or testosterone gel, and anastrozole (to suppress the conversion of testosterone to estradiol). Changes in the percentage of body fat and in lean mass were the primary outcomes. Subcutaneous- and intraabdominal-fat areas, thigh-muscle area and strength, and sexual function were also assessed. The results showed that the percentage of body fat increased in groups receiving placebo of 1.25g or 2.5g of testosterone daily without anastrozole (mean testosterone level, 44±13 ng per deciliter, 191±78 ng

This study was a secondary analysis of the prospectively collected Veterans Affairs National Surgical Quality Improvement Program (VASQIP) database. The objective was to determine the rates of major medical complications, wound complications, and mortality among patients undergoing surgery for lumbar stenosis and to examine risk factors for these complications. The authors identified patients who underwent surgery for a primary diagnosis of lumbar stenosis between 1998 and 2009 from the

per deciliter, and 337±173 ng per deciliter, respectively). Lean mass and thigh-muscle area decreased in men receiving placebo and in those receiving 1.25g of testosterone daily without anastrozole. Leg-press strength fell only with placebo administration. In general, sexual desire declined as the testosterone dose was reduced. The authors conclude that the amount of testosterone required to maintain lean mass, fat mass, strength, and sexual function varied widely in men. N Engl J Med. 2013 September. PMID: 24024838

Richness of human gut microbiome correlates with metabolic markers Published in Nature, this study describes the idea of an impending global metabolic health crisis provoked by an obesity epidemic. The authors report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. The authors found two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. The results show that they contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. The author conclude that their classifications based on the variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at an increased risk of progressing to adiposityassociated co-morbidities. Nature. 2013 August. PMID: 23985870

VASQIP database. They created a composite of major medical complications, including acute myocardial infarction, stroke, pulmonary embolism, pneumonia, systemic sepsis, coma, and cardiac arrest. The results showed that among 12,154 eligible patients, major medical complications occurred in 2.1%, wound complications in 3.2%, and 90-day mortality in 0.6%. Major medical complications were strongly associated with age. Insulin use, chronic corticosteroid use, and preoperative functional status were also significant predictors. Fusion procedures were associated with higher complication rates than decompression alone. In logistic regressions, American Society of Anesthesiologists (ASA) class and age were the strongest predictors of major medical complications. The authors conclude that ASA class, age, type of surgery, insulin or corticosteroid use, and functional status were independent risk factors for major medical complications. Spine (Phila Pa 1976). 2013 June. PMID: 23778366 November / December 2013 l www.ihpmagazine.com 11

research news Mediterranean diet, cognitive function, and dementia: a systematic review This systematic review synthesized the studies on the association between adherence to the Mediterranean diet and cognitive function or dementia. The authors conducted a systematic review of 11 electronic databases (including Medline) of published articles up to January 2012. Reference lists, selected journal contents, and relevant websites were also searched. Study selection, data extraction, and quality assessment were performed independently by two reviewers using predefined criteria. Studies were included if they examined the association between a Mediterranean diet adherence score and cognitive function or dementia. The results showed there were twelve eligible papers (11 observational studies and one randomized controlled trial) were identified, describing seven unique cohorts. Despite methodological heterogeneity and limited statistical power in some studies, there was a reasonably consistent pattern of associations. Higher adherence to Mediterranean diet was associated with better cognitive function, lower rates of cognitive decline, and reduced risk of Alzheimer disease in nine out of 12 studies, whereas results for mild cognitive impairment were inconsistent. The authors conclude that published studies suggest a greater adherence to Mediterranean diet is associated with slower cognitive decline and lower risk of developing Alzheimer disease. Epidemiology. 2013 July. PMID: 23680940

Risks of hormone replacement therapy and breast cancer This study analyzed the association between hormone replacement therapy (HRT) and break cancer risk as modified by patient factors. The authors analyzed 1642824 screening mammograms with 9300 breast cancer cases in postmenopausal women aged 45 years or older derived from the Breast Cancer Surveillance Consortium, a longitudinal registry of mammography screening in the United States. Multiple imputation methods were used to accommodate missing data for HRT use (14%) and other covariables. The results showed HRT use was associated with greater than 20% increased risk in white (OR = 1.21; 95% CI = 1.14 to 1.28), Asian (OR = 1.58; 95% CI = 1.18 to 2.11), and Hispanic women (OR = 1.35; 95% CI = 1.09 to 1.67) but not black women (OR = 0.91; 95% CI = 0.72 to 1.14). In women with low/normal BMI and extremely dense breasts, HRT use

was associated with the highest breast cancer risk (OR = 1.49; 95% CI = 1.21 to 1.83), compared with nonusers. The authors also found that in overweight/ obese women with less-dense breasts, no excess risk was associated with HRT use (adjusted ORs = 0.96 to 1.03). J Natl Cancer Inst. 2013 September. PMID: 24003037

12 www.ihpmagazine.com l November / December 2013

Systematic review of vitamin D status in populations worldwide This study examined the relationship between vitamin D deficiency and osteoporosis, risk of cancer, and cardiovascular disease. In a systematic literature review using the Medline and EMBASE databases, the authors identified 195 studies conducted in forty-four countries involving

more than 168,000 participants. Mean population-level 25(OH)D values varied considerably across the studies (range 4·9-136·2 nmol/l), with 37.3 % of the studies reporting mean values below 50 nmol/l. The highest 25(OH)D values were observed in North America. Although age-related differences were observed in the Asia/ Pacific and Middle East/Africa regions, they were not observed elsewhere and sex-related differences were not observed in any region. Substantial heterogeneity between the studies precluded drawing conclusions on overall vitamin D status at the population level. Exploratory analyses suggested that newborns and institutionalized elderly from several regions worldwide appeared to be at a generally higher risk of exhibiting lower 25(OH)D values. The authors conclude substantial details on worldwide patterns of vitamin D status at the population level and within key subgroups are needed to inform public health policy development to reduce risk for potential health consequences of an inadequate vitamin D status. Br J Nutr. 2013 August. PMID: 23930771

research news Increased risk for irritable bowel syndrome after acute diverticulitis

Childhood adversity and inflammatory processes in youth This prospective study used longitudinal data from the Avon Longitudinal Study of Parents and Children to examine the associations between acute adverse events at seven time points prior to age eight and inflammation at ages 10 and 15. Inflammatory markers at age 10 included interleukin-6 (IL-6; N=4655) and C-reactive protein (CRP; N=4647), and CRP was measured again at age 15 (N=3286). We further evaluated whether body mass index (BMI), depression, or cigarette smoking mediated associations between adverse events and inflammation. The results showed that adverse events in

middle childhood (occurring between ages six to eight), as well as cumulative adversity from birth to eight years, were associated with higher levels of IL-6 and CRP at age 10. Adverse events reported in early childhood (1.5years) or middle childhood, and cumulative adversity from birth through eight years predicted increased levels of CRP at age 15, and these associations persisted after adjustment for CRP at age 10. Some, but not all, of these associations were mediated by BMI. The authors conclude that exposure to adverse events prior to age eight is associated with elevated inflammation at age 10 and in mid-adolescence. Psychoneuroendocrinology. 2013 February. PMID: 22727478

This study investigated whether diverticulitis might lead to IBS. The authors compared the incidence of IBS and functional bowel and related affective disorders among patients with diverticulitis. They performed a retrospective study of patients followed up for an average of 6.3 years at a Veteran’s Administration medical center. Patients with diverticulitis were identified based on International Classification of Diseases, 9th revision codes, selected for the analysis based on chart review and matched with patients without diverticulosis. They excluded patients with prior IBS, or prior functional

Acute sleep deprivation increases food purchasing in men This study investigated if acute sleep deprivation affects food purchasing choices in a mock supermarket. On the morning after one night of total sleep deprivation (TSD) or after one night of sleep, 14 normal-weight men were given a fixed budget (300 SEK-approximately 50 USD). They were instructed to purchase as much as they could out of a possible 40 items, including 20 high-caloric foods (>2 kcal/g) and 20 low-caloric foods (<2 kcal/g). The prices of the high-caloric foods were then varied (75%, 100% (reference price), and 125%) to determine if TSD affects the flexibility of food purchasing. Before the task, participants received a standardized breakfast, thereby minimizing the potential confound produced by hunger. In addition, morning plasma concentrations of the orexigenic hormone ghrelin were measured under fasting conditions. The results showed that independent of both type of food offered and price condition, sleep-deprived men purchased significantly more calories (+9%) and grams (+18%) of food than they did after one night of sleep. Morning plasma ghrelin concentrations were also higher after TSD. However, this increase didn’t correlate with the effects of TSD on food purchasing. The authors conclude acute sleep loss alters food purchasing. Obesity (Silver Spring). 2013 August. PMID: 23908148

bowel disorders, or mood disorders. They identified patients who were diagnosed with IBS or functional bowel disorders after the diverticulitis attack and controls who developed these disorders during the study period. The results showed that cases were 4.7-fold more likely to be diagnosed later with IBS, 2.4-fold more likely to be diagnosed later with a functional bowel disorder, and 2.2-fold more likely to develop a mood disorder than controls. The authors conclude that patients with diverticulitis could be at risk for later development of IBS and functional bowel disorders. Diverticulitis appears to predispose patients to long-term gastrointestinal and emotional symptoms after resolution of inflammation. Clin Gastroenterol Hepatol. 2013 March. PMID: 23524129 November / December 2013 l www.ihpmagazine.com 15

research news

This follow-up study compared ten men and 25 external controls who had biopsy-proven low-risk prostate cancer and had chosen to undergo active surveillance. Eligible participants were enrolled between 2003 and 2007 from previous studies and selected according to the same criteria. Men in the intervention group followed a program of comprehensive lifestyle changes (diet, activity, stress management, and social support), and

the men in the control group underwent active surveillance alone. The authors took blood samples at 5 years and compared relative telomere length and telomerase enzymatic activity per viable cell with those at baseline, and assessed their relation to the degree of lifestyle changes. The results showed that relative telomere length increased from baseline by a median of 0.06 telomere to single-copy gene ratio (T/S) units (IQR-0.05 to 0.11) in the lifestyle intervention group, but decreased in the control group (-0.03 T/S units, --.05 to 0.03, difference p=0.03). Adherence to lifestyle changes was significantly associated with relative telomere length after adjustment for age and the length of follow-up. The authors conclude that a comprehensive lifestyle intervention was associated with increases in relative telomere length after 5 years of follow-up. Lancet Oncol. 2013 September. PMID: 24051140

This study evaluated the association between migraine without aura (MO) and migraine with aura (MA) and 3 types of structural brain abnormalities detected by MRI: white matter abnormalities (WMAs), infarct-like lesions (ILLs), and volumetric changes in gray and white matter (GM, WM) regions. In this systematic review, the results showed that six population-based and 13 clinic-based studies were identified. The studies suggested that structural brain changes, including WMAs, silent ILLs, and volumetric changes in GM and WM regions, were more common in migraineurs than in control groups.

The results were strongest for MA. The meta-analysis of WMAs showed an association for MA (OR 1.68; 95% CI 1.07-2.65; p = 0.03) but not for MO (OR 1.34; 95% CI 0.961.87; p = 0.08). The association of ILLs was greater for MA (OR 1.44; 95% CI 1.02-2.03; p = 0.04) than for MO, but no association was found for MA (p = 0.52) and MO (p = 0.08) compared to controls. The authors conclude that the data suggest that migraine may be a risk factor for structural changes in the brain. They argue additional longitudinal studies are needed to determine the differential influence of MO and MA. Neurology. 2013 August. PMID: 23986301

16 www.ihpmagazine.com l November / December 2013

Gymnemic acid inhibits hyphal growth and virulence in Candida albicans Candida albicans is an opportunistic and polymorphic fungus that causes mucosal, disseminated, and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm

formation. Nontoxic small molecules that inhibit C. albicans yeast-tohypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. In this study, the authors identified the triperpenoid saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves. The results showed that purified GAs had no effect on the growth and viability of C. albicans yeast cells, but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. In addition, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. PLoS ONE. 2013. PMID: N/A

PhotosÂŠiStockphoto.com

Effect of lifestyle changes Migraine and structural on telomerase activity and changes in the brain: a telomere length systematic review and meta-analysis

HairGrow Tech IHP FullPg.qxp:Educational ad

10/2/12

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

Twice the Strength! Double the Power! Bio-Fen® Plus for Men: The mechanism that causes AGA in men follows the same pathway that results in benign prostatic hyperplasia (BPH). For example, the prescription drug finasteride also works by blocking the enzyme 5αreductase and is used as a treatment for both BPH and AGA. For AGA it is marketed under the brand name of Propecia, but the exact same molecule for BPH is sold under the name of Proscar. Hair Grow Technology’s Bio-Fen® product line is continually moving forward! We are introducing our two latest versions; Bio-Fen® Plus for Men and Bio-Fen® Plus for Women. These products have been assigned Natural Product Numbers (NPN’s) by the Natural Health Products Directorate (NHPD) of Health Canada. We recognize that both men and women experience androgenic alopecia (AGA, or male / female pattern baldness) and have made some improvements to the original formulation based on the latest science to address their specific needs. You will notice that we now have additional complementary (Health Canada Approved) health claims on each product.

What causes hereditary hair loss? Each hair grows from a pocket in the skin called the hair follicle. During its growing phase the follicle has a bulb-shaped bottom, the center of which is called the dermal papilla. The paplla is fed by very small blood vessels, which bring it food, oxygen and remove wastes. The papilla is highly sensitive to hormones and chemicals secreted by the body (or ingested as a medicine) which impacts hair growth It is believed that some individuals have a genetic predisposition to a receding hairline (most common in men) or hair (follicle) thinning over larger areas of the scalp (more common in women). These conditions result from hormonal changes caused by an enzyme in the dermal papilla called 5-alpha-reductase. This enzyme breaks down the hormone testosterone into dihyrotestosterone (DHT). Over a period of time, an over abundance of DHT causes the hair follicle to degrade and shortens the active phase of the hair, eventually leading to thinner hair and eventual hair loss.

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

As before, the saw palmetto extract inhibits the enzyme 5-alpha reductase, and this action slows down the conversion of testosterone to dihydrotestosterone (or DHT) – the overabundance of which causes the miniaturization of hair follicles. This activity of the saw palmetto also helps to relieve the urinary symptoms of mild to moderate BPH for men. The saw palmetto that originally was an extract standardized to 45% free fatty acids, esters, and sterols while the new formula is a 4:1 extract to support the BPH claim. The product still contains these molecules for hair loss, but they are now at proprietary amounts based on our research so that the competition cannot duplicate our formula.

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

Bio-Fen® Plus for Women: The women’s formula is almost the same as the men’s formula. The mechanisms and results for the women formula is the same. The only difference is it contains silicon and iron instead of saw palmetto. Silicon has been shown to contribute to hair shaft strength and thus healthy hair growth. It also contains iron which helps prevent iron deficiency. A number of studies have related sub-clinical iron deficiency in women to diffuse hair loss/alopecia. The increased amount of SDG and other revisions to the regulations allow us to make some additional health claims for Bio-Fen® Plus for Women.

Available at Health Food Stores and Independent Pharmacies

Hair Grow Technology Inc.

•

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

How long must I use Bio-Fen® Plus? Bio-Fen® Plus for Men capsules are usually effective at stopping hair loss within the first two months. However, since healthy hair grows only about 1 cm each month, it may take up to three months before you notice that hair growth is increased or the rate of hair loss is decreased. Anyone experiencing new growth should see it within four months. In some people the original pigmentation may come back. Once you stop completely your hair growth pattern will slowly go back to the point where you started. However, some people may be able to go with a lower maintenance dose.

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

How safe is Bio-Fen® Plus? The ingredient combination in Bio-Fen® Plus is generally safe for most adults. However, the following cautions are advised: For Men: Consult a health care practitioner prior to use to exclude a diagnosis of prostate cancer, or if you have diabetes. For BPH or elevated blood lipid levels, consult a health care practitioner if symptoms persist or worsen. People sensitive to niacin may experience flushing of the skin that is generally mild and transient. Discontinue use if you experience hypersensitivity to flax, such as an allergy (may occur in rare cases). For Women: Consult a health care practitioner prior to use if you are pregnant or if you have diabetes. Consult a health care practitioner if elevated blood lipid levels persist or worsen. People sensitive to niacin may experience flushing of the skin that is generally mild and transient. Discontinue use if you experience hypersensitivity to flax, such as an allergy (may occur in rare cases). Because of the iron content, some people may experience constipation, diarrhea and/or vomiting. Keep out of the reach of children. There is enough iron in this package to seriously harm a child.

1-866-424-7745 • www.biofen.com

PRODUCT MONOGRAPH Bio-Fen Bio-Fen Plus is an oral natural health product used in the treatment of hereditary androgenic alopecia (AGA) for male or female pattern baldness. Without treatment, AGA is progressive, and causes social distress for in many men and women (Sinclair 1998). Bio-Fen Plus contains extracts BIO-FEN Menaffected and Women of fenugreek seeds, saw palmetto berries and flax lignans, as well as specific vitamins. Each ingredient is known to possess inhibitors of the enzyme 5α-reductase. are responsible for relieving symptoms associated withPlus hereditary AGA. Bio-Fen represents aThese line of inhibitors products approved by Health Canada for hair growth and restoration. Bio-Fen for Men and Bio-Fen Plus for Women are both oral natural health One of the primary causes hair loss is and a high level of hereditary the maleandrogenic hormonealopecia dihydrotestosterone (DHT) within the hair follicle (Vierhapper, 2001). products (NHPs) which support hairofgrowth in men women with (AGA), or female/male pattern baldness. Bio-Fen contains a combination of herb extracts andwith vitamins & minerals that are known inhibit the enzymeof 5 androgen -reductase (5AR), a keyto pathway in the progression of AGA. catalyzes the enzymatic For people AGA, their follicles have atogreater number receptors whichimplicated DHT attaches. 5-α-reductase conversion of testosterone to dihydrotestosterone, which binds to the receptor five-fold more avidly than the parent compound (Sinclair 1998). AGA Pathophysiology One of the primary causes of hair loss is a high level of the male hormone, dihydrotestosterone (DHT) within the hair follicle (Hoffmann 2002). DHT is produced from Saw palmetto repens) testosterone in the(Serenoa testes (males), the adrenal glands, and the follicle. After a period of time, anVitamins over abundance of DHT causes the hair follicle to degrade and shortens the active phase of the hair,(lipophillic) eventually leading to thinning hairbeen and eventual Thereinhibitor is a familial In tendency forstudy stepwise the hair follicle and an increase in the calcium ratio a Polish of miniaturization 46 women whoof had symptoms of diffuse alopecia, Standardized Serenoa extract has found tohair be loss. a potent of of telogen (resting phase) to anagen (growthtissue phase)DHT. hairs, which is promoteddose by systemic effects of was androgens. Althou gh everyone thosemg with pantothenate orally administered twiceproduces a day inDHT, dosesonly of 100 fora four to 5α-reductase, resulting in decreased An open-label, responseand local higher of androgen in their binding sitesof fora DHT, and greater five androgen sensitivity experience hairinjected loss (Prager 5AR forrepeated the months, and vitamin B6 was every2002). day for 20istoresponsible 30 days and studynumber was conducted onreceptors 42 healthy maleshair to follicles, determine the effect combination conversion of testosterone to dihydrotestosterone, binds to the sameon androgen but with five-fold greater(Brzezińska-Wcisło affinity. (Hoffmann 2001). 2002, Trueb after six months It was2002) determined that vitamin again of carotenoid astaxanthin and saw palmettowhich berry lipid extract DHT receptor, and

testosterone levels (Angwafor 2008). The men were divided into two groups:

B6 administered parenterally for a few weeks induces improvement in the hair

Flax condition in subset women and Flax reduces hair are loss. onelignans groupinhibit received 800 mg/day of the combination supplement the other Flax the enzyme 5AR, thus balancing formation of the maleand hormones that are responsible fora hair lossof(Evans 1995). lignans converted by the body to group received 2000 mg/daywith of the supplement for 14 days. ANOVA-RM enterolactones, which compete estrogen and testosterone for receptor binding,showed and increase sex hormone binding globulin (SHBG), resulting in lower levels of free (ie active) significant within-group increases in serum testeosterone significant estrogen and testosterone. Flaxseed has been shown total to reduce serum levelsand of 17-beta-estradiol and estrone sulfate (Hutchins 2001), and results in a shift in estrogen metabolism to Medicinal Ingredients Dose Per Capsule decreases serum DHT baseline in both favor the lessin biologically activefrom estrogens (Brooks 2004).dose groups (P=0.05). There

was no significant difference between dose groups with regard to the increase of

Fenugreek (Trigonella foenum graecum)

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

Saw palmetto berry extract containing

160 mg

Another study tested liposterolic extract of Serenoa repens (LSESr) and beta45% free fatty acids Saw Palmetto (men’s product) sitosterol inextract the treatment of males (23-64 of age)resulting with mild to moderate AGA. Saw palmetto is a potent inhibitor of 5 years -reductase, in decreased tissue DHT (Prager 2002). In a pilot study of 26 men with mild to moderate AGA, treatment with Flax lignans, standardized toblinded 20% assessors (Prager 2002). In a meta Six of 10 (60%) subjectssaw were rated asextract improved at and the beta-sitosterol final visit, thus50mg establishing a combination of lipophilic palmetto 200mg improved symptoms by up to 60%, as scored by 100 mg diglucoside the effectiveness of 5α-reductase inhibitors AGA (Prager 2002). Chronic analysis by the Cochrane group, saw palmetto hasagainst also been found to be effective as a treatment secoisolariciresinol for symptoms of BPH (Wilt 2002). (SDG) inflammation of the hair follicle is considered to be a contributing factor for AGA. A

D-calcium pantothenate (Vitamin B5) 10.40 mg Silica (women’s product) study by Chittur et al sought to determine whether blockade of inflammation using Silica is a and tracetwo mineral that has been found to increase hydroxyproline in connective tissue (Barel 2005). In a randomized, double blind, placebo controlled study, 50 LSESr anti-inflammatory agents (carnitine and thiocticconcentration acid) could alter Niacinamide (Vitamin B3) 10.25 mg women with damaged skin weremarkers treated orally with 10mg silica as orthosilicic the expression of molecular of inflammation (Chittur 2009). It acid was (OSA) found daily for 20 weeks. The treatment group reported a significant decrease in visual analog scale ratings of hair brittleness (Barel 2005). A second randomized, double blind, placebo controlled trial conducted in 50 women with brittle hair found that 10mg silica as OSA Pyridoxine HCl (Vitamin B6) 2 mg that the combination suppressed lipopolysaccharide-activated gene expression of for 9 months significantly improved hair elasticity, breakage, and diameter (thickness) (Wickett 2007). chemokines associated with pathways involved in inflammation and apoptosis.

Riboflavin (Vitamin B2)

1.58 mg

Folic acid

0.095 mg

study thatcell 5-alpha inhibitors in combination withmetabolism. B The vitamins are concluded support healthy growthreductase and division, and facilitate optimal hormone

blockade of inflammatory processes could represent a new two-pronged approach Medicinal ingredients per capsule in both the men’s and women’s: in the treatment of AGA.

Fenugreek (Trigonella foenum graecum) seed extract 4:1 ....................................................260 mg Biotin 400 mcg equiv 1040mg) Fenugreek (dry Seeds Flax lignans, standardized to 50% SDG ...............................................................................100 mg Non-Medicinal Ingredients Fenugreek seeds contain 5% to 30% protein, steroid saponins, sterols, flavonoids d-calcium pantothenate (Vitamin B5) ..................................................................................10.4 mg and alkaloids (notably trigonelline and choline). Steroid saponins bind and Niacinamide (Vitamin B3) ...................................................................................................10.3 mg Inert microcrystalline cellulose and vegetable-based magnesium eliminateHCl extra cholesterol and hormones in the body; DHT is made from mg Pyridoxine (Vitamin B6) ...............................................................................................2.0 stearate in a veggie-based capsule testosterone, which in turn is made from cholesterol. Therefore, when excess mg (Vitamin B2)is.......................................................................................................1.6 Riboflavin is eliminated, less DHT can be made (Stark 1993). In a study of 20 mcg cholesterol Folic acid ..............................................................................................................................95 Recommended adult dose: One capsule per day adults....................................................................................................................................250 who consumed 12.5g and 18.0g of germinated fenugreek seed powder for Biotin mcg

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

Men’s also has: cholesterol and low-density lipoprotein (LDL) levels (Sowmya 1999). Saw palmetto berry extract 4:1 .............................................................................................125 mg (dry equiv. 500 mg) Flax lignans

Flax reduces the amount of DHT produced by reducing cholesterol levels in the

Women’s also has: body.(silicon A meta-analysis of 28 studies between 1990 and 2008 showed that flaxseed mg Silicon dioxide) ........................................................................................................40 significantly reduces circulating total and LDL-cholesterol concentrations (Pan mg Iron (ferric citrate) ................................................................................................................20

2009). Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L

Recommended use:0.00 one mmol/L) capsule twice capsules perCI: bottle). Bio-Fen® Plus capsules are usually effective (95% CI: -0.20, and daily 0.08 (60 mmol/L (95% -0.16, 0.00 mmol/L), at respectively. stopping hair Significant loss within the first two were months. Anyonewith experiencing new growth reductions observed whole flaxseed (-0.21should and see it within four months. Once Bio-Fen is stopped, the hairand growth pattern will and slowly return to its original point, however some people may -0.16 mmol/L, respectively) lignan (-0.28 -0.16 mmol/L, respectively) besupplements able to continue with a lower maintenance dose. (Pan 2009). Bio-Fen has been approved by Health Canada and has received a unique NPN number. In addition to being approved for hair growth applications, Bio-Fen has been approved for additional health benefits. Angwafor F III, Anderson ML. An open label, dose response study to determine the effect of a dietary supplement on dihydrotestosterone, testosterone and estradiol levels in healthy males. J Int Soc Sports Nutr 2008;5:12.

Contraindications: The ingredient combination in Bio-Fen Plus for Men/Women is generally safe for most adults. Bio-Fen should not be used by patients withB6 diabetes, or known hypersensitivity to any ingredients. Brzezińska-Wcisło L. Evaluation of vitamin and calcium pantothenate effectiveness on hair growth from clinical and trichographic aspects for treatment of diffuse alopecia in women. Wiad Lek 2001;54:11-8.

References Chittur S, Parr B, Marcovici G. Inhibition of inflammatory gene expression in keratinocytes using a composition containing carnitine, thioctic acid and saw palmetto extract. Evid Based Brooks JD, et al. Am J Clin Complement Alternat Med Nutr. 2009. 2004 Feb;79(2):318-25. Evans BA, et al. 1995 Nov;147(2):295-302. Pan A, Yu D, Demark-Wahnefried W, Franco OH, Lin X. Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr 2009;90:288-97. Hoffmann R. Clin Exp Dermatol. 2002 Jul;27(5):373-82. 2001;39(1):58-65. Hutchins AM,et al.K, Nutr Cancer. Prager N, Bickett French N, Marcovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the Prager N, etof al.androgenetic 2002 Apr;8(2):143-52. treatment alopecia. J Altern Complement Med 2002;8:143-52. Trüeb RM. Exp Gerontol. 2002 Aug-Sep;37(8-9):981-90. Serenoa repens monograph. Alternative Medicine Review 1998;3:227-9. Wickett RR, et al Arch Dermatol Res. 2007 Dec;299(10):499-505. Wilt T et al. Database Syst Rev. 2002;(3):CD001423. Sinclair R. Cochrane Male pattern androgenetic alopecia. BMJ 1998;317:865-9. Sowmya P, Rajyalakshmi P. Hypocholesterolemic effect of germinated fenugreek seeds in human subjects. Plant Foods Hum Nutr 1999;53:359-65. Stark A, Madar Z. The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on bile acid absorption and cholesterol levels in rats, Br J Nutr 1993;69:277-87. Vierpper H, Nowotny P, Maier H, Waldhausl W. Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/ dilution and mass spectrometry. J Clin Endocrinol Metab 2001;86:5762-4.

IHPAPR2012_9444_BioFen_Hairgrow_FP.indd 2

4/5/12 1:18:17 PM

industry news Lithium in the brain: Neutrons show accumulation of antidepressant in brain

Experim ents with neutrons at the Technische Universität München (TUM) show that the antidepressant lithium accumulates more strongly in white matter of the brain than in grey matter. This leads to the conclusion that it works differently from synthetic psychotropic drugs. The tissue samples were examined at the Research Neutron Source Heinz Maier-Leibnitz (FRM II) with the aim of developing a better understanding of the effects this substance has on the human psyche. At present lithium is most popular for its use in rechargeable batteries. But for decades now, lithium has also been used to treat various psychological diseases such as depressions, manias and bipolar disorders. But, the exact biological mode of action in certain brain regions has hardly been understood. It is well known that lithium lightens moods and reduces aggression potential. Because it is so hard to dose, doctors have been reluctant to prescribe this “universal drug”. Nonetheless, a number of international studies have shown that a higher natural lithium content in drinking water leads to a lower suicide rate in the general population. Lithium accumulates in the brains of untreated people, too. This means that lithium, which has so far been regarded as unimportant, could be an essential trace element for humans. This is what Josef Lichtinger is studying in his doctoral thesis at the Chair for Hadron and Nuclear Physics (E12) at the Technische Universität München. From the Institute for Forensic Medicine at the Ludwig-Maximilians-Universität Munich (LMU) he received tissue samples taken from patients treated with lithium, untreated patients and healthy test persons. The physicist exposed these to a focused cold neutron beam of greatest intensity at the measuring station for prompt gamma activation analysis at FRM II. Lithium reacts with neutrons in a very specific manner and decays to a helium and a tritium atom. Using a special detector developed by Josef Lichtinger, traces as low as 0.45 nanograms of lithium per gram of tissue can be measured. “It is impossible to make measurements as precise as those using the neutrons with any other method,” says Jutta Schöpfer, forensic scientist at the LMU in charge of several research projects on lithium distribution in the human body.

Ottawa Life Launches 6-Part Year-Long Series on the Ottawa Integrative Cancer Centre The Ottawa Integrative Cancer Centre (OICC) opened in 2011 as a research and new cancer care centre. The goal is prevention and improving the lives of those who are living with cancer. It works collaboratively with other health professionals and practices, integrating the use of naturopathic and other compatible whole-person treatments with standard cancer care to reach their goals. The OICC Founder and Executive Director, Dugald Seely, was selected as one of the Top 25 People in the Capital in 2013 by Ottawa Life for his vision and leadership in starting the first integrative cancer care and research centre in central and eastern Canada.

Highland Therapeutics announces positive interim results of HLD-200 in ADHD patients

Highland Therapeutics Inc., a specialty pharmaceutical company leveraging its proprietary technologies to optimize the delivery of previously approved drug products, announced that its wholly owned subsidiary has generated positive interim Phase I/II results from an ongoing study of HLD-200 - a novel formulation of methylphenidate being developed to treat the symptoms associated with Attention-Deficit/Hyperactivity Disorder (ADHD). The study, “A Phase I/II, Single Center, Single-Treatment, Open-Label, Adaptive Clinical Trial Design Examining the Pharmacokinetic Effects of up to Two Separate HLD-200 Modified Release Formulations of Methylphenidate in Adolescent and Pediatric Subjects with Attention-Deficit Hyperactivity Disorder”, is expected to be completed in the fourth quarter of 2013. Based on an interim analysis of data from adolescent patients, the study demonstrated that the active pharmaceutical ingredient (API), methylphenidate, was consistently delivered in a manner that allows for dosing of HLD-200 prior to bedtime, with the objective of controlling the symptoms of ADHD immediately upon wakening. Further, a comparative analysis of the pharmacokinetic (PK) profiles suggests that HLD-200 could have an extended duration of effect when compared to other once-daily methylphenidate medications. Notably, patients enrolled in the study did not report any significant adverse events, which suggests that HLD-200 could potentially have a better safety profile than other available medications to treat ADHD.

Vita Health Products issues voluntary recall of products

Vita Health Products Inc. announced the voluntary recall of three lots of Pharmasave Extra Strength Ibuprofen Liquid Capsules, 12 count and Remedy’s Rx Cold + Sinus, 20 count. The product is being recalled due to a labeling design error. The finished good is a labeled bottle in a box. The inner label correctly states in French and English that the product is not child resistant. The outer box correctly states the product is not child resistant in English but incorrectly states “Bouchon à l’épreuve des enfants” in French which translates to “Child Resistant Cap”. The outer box and inner label state ‘CAUTION: KEEP OUT OF THE REACH OF CHILDREN. There is enough drug in this package to seriously harm a child’ in French and English in prominent red text. Once Vita Health became aware of the issue, the company immediately notified Health Canada and began the recall process. To date there have been no adverse events reported concerning the product. Consumers who have any of this product in their possession should return the product to the place of purchase or call 1-(800)-665-8820, Monday-Friday 9 am-5:30 pm EST for further instruction.

November / December 2013 l www.ihpmagazine.com 19

industry news KLOX Technologies announces approval in Canada of acne vulgaris treatment

KLOX Technologies Inc. announced the approval in Canada of the Klox Biophotonic System (also known as the Lumigel Cleanse System) for the treatment of acne vulgaris after receiving this week a Medical Device License from the Therapeutic Products Directorate - Medical Devices Bureau of Health Canada. The Lumigel Cleanse System is a first-in-class innovative acne vulgaris treatment which has shown in clinical trials a superior profile in terms of combined safety and efficacy. “KLOX is proud to receive its first approval here in Canada. This important milestone fits perfectly into our regulatory strategy that we are pursuing around the world and to that end the company has also filed in Europe for a CE mark,” said Dr. Lise Hébert, President and CEO of KLOX. With this new, cutting edge topical product, of a different category than photodynamic therapy, KLOX is now actively pursuing its goals which are two-fold: to create important returns for its shareholders and to advance its large pipeline of products for unmet needs in dermatology. Acne vulgaris is a chronic disease that can have devastating physical, social and psychological effects on those who suffer from it, particularly in moderate to severe cases. Acne vulgaris affects over 5 million people in Canada, and approximately 150 million people worldwide. It accounts for over 30% of dermatology visits and over 40% of those suffering from this disease are looking for treatments with a better safety and efficacy profile than what is currently available. Many of the topical, oral and photodynamic treatments for acne vulgaris are characterized by inconsistent efficacy/persistence, systemic treatment schedules, lower patient tolerability and in most cases, side-effects. “Based on the new technology, the KLOX Lumigel Cleanse System is a first-in-line Class II medical device with an unmatched clinical profile in terms of efficacy and safety. Patients will appreciate its visible and long-lasting effects, as demonstrated clinically, with the benefit of being non-invasive in nature. On the other hand, practitioners will be able to offer an easy-to-administer and accessible treatment option,” said Dr. Steven Bernstein, Chief of Dermatology Surgery at the University of Montreal Hospital Center (CHUM).

Gamma-Dynacare Medical Laboratories announces acquisition in genetics

Gamma-Dynacare Medical Laboratories (Gamma-Dynacare) announced that it has completed the acquisition of a controlling interest in Impact Genetics Inc. (Impact Genetics), a Toronto-based laboratory specializing in high-complexity, disease-specific genetic testing. “We welcome this opportunity to strengthen Gamma-Dynacare’s position as a leading Canadian reference laboratory,” said Naseem Somani, President and Chief Executive Officer, Gamma-Dynacare Medical Laboratories. “Experts around the world seek out the specialized genetic testing expertise of Impact Genetics. This investment brings to Gamma-Dynacare expanded capabilities in molecular medicine, oncology and genetic testing for rare diseases that will enhance our continued growth in the field of personalized medicine.” Impact Genetics is recognized by oncologists and geneticists around the world as a leader in genetic testing for rare diseases. With a test menu including Retinoblastoma RB,Hereditary Hemorrhagic Telangiectasia (HHT), Von Hippel-Lindau Syndrome VHL and Gene Copy Number Analysis, Impact Genetics serves clients throughout North America, Asiaand Europe. New tests for Uveal Melanoma and Inherited Leukemia will soon be launched. “This exciting partnership will provide Canadians with better genetics services and build on local expertise and talent in this rapidly expanding market,” said Franny Jewett, CEO, Impact Genetics. Over the coming months, Impact Genetics’ operations will move to Gamma-Dynacare’s centre of excellence for pathology, immunopathology, genetics and pharmacogenomics testing in Bowmanville Ontario, near Toronto. Ms. Jewett, Medical Director Dr. Brenda Gallie and the entire Impact Genetics team will remain in their respective roles with the company.

Valeant Pharmaceuticals announces approval of Jublia® for Onychomycosis

Valeant Pharmaceuticals International, Inc. announced today that its wholly owned subsidiary, Valeant Canada LP, has received notice that the New Drug Submission for Jublia® has been approved from the Canadian regulatory authority, Health Canada. Jublia® (efinaconazole 10% topical solution) is indicated for the treatment of mild to moderate onychomycosis, a common and destructive nail infection caused predominantly by dermatophyte fungi. The only currently approved topical treatments are lacquers with limited efficacy. Oral treatments are limited by drug interactions and numerous safety concerns including the potential for acute liver injury. Laser treatments only improve the appearance of the nail. “Jublia® represents the first new topical onychomycosis treatment approved in more than a decade, and we are very excited to bring this new treatment option to patients in Canada,” said J. Michael Pearson, chairman and chief executive officer. “An effective topical therapy like Jublia® is a logical treatment option to avoid drug interactions and systemic side effects, and we believe Jublia® will position us well to address a growing unmet need.” “There is a pressing need for an effective topical therapy for mild to moderate onychomycosis, especially in individuals who cannot tolerate or are not candidates for an oral antifungal,” stated Dr. Aditya K. Gupta, M.D., Ph.D., F.A.A.D., F.R.C.P(C), Professor, Department of Medicine, University of Toronto, Canada. “The Phase III clinical trial data for Jublia® show that it is an effective and safe topical antifungal therapy for mild to moderate onychomycosis. Jublia® is likely to become widely prescribed by dermatologists, family physicians and other healthcare providers for the treatment of onychomycosis”

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

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PRODUCT mOnOgRaPh

PRODUCT MONOGRAPH OIL OF OREGANO

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

Human studies

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

Animal and In vitro studies

Carvacrol for oral candidiasis in immunocompromised rats was found to be as effective as treatment with Nystatin, reducing the number of colony forming units (CFU’s) and completely clearing hyphae from oral surfaces when given for 8 days (Chami 2004). In vitro, carvacrol was determined to exert an inhibitory effect against 6 different strains of Candida species primarily due to extensive lesion of the plasma membrane (Salgueiro 2003). Carvacrol has potent antimicrobial activity against several microbial species, including Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Psuedomonas aeruginosa, Candida albicans, and Aspergillus niger; out of these, Candida albicans has been found most susceptible (Santoyo 2006). Carvacrol and thymol are thought to exert an additive effect by disrupting bacterial membrane integrity (Lambert 2001). Oregano has been shown to inhibit Methicillin resistant strains of Staph.

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

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

Toxicology

Essential oil extracts are categorically known to be toxic in high doses, and are therefore typically given in drop doses; essential oils should not be used internally by pregnant or breastfeeding women. Animal studies to date, however, indicate relative safety of Oregano oil. Carvacrol was shown to be hepatoprotective against ischemia and reperfusion injury in rats; both carvacrol and silymarin had similar beneficial effects on AST and ALT levels (Canbek 2007). Carvacrol also increased liver regeneration rate in rats after partial hepatectomy (Uyanoglu 2008). Mutagenicity studies of carvacrol show only weak activity; carvacrol is excreted in urine after 24 hours in large quantities, unchanged or as glucoronide and sulphate conjugates (De Vincenzi 2004).

References

Canbek M, Uyanoglu M, Bayramoglu G, Senturk H, Erkasap N, Koken T, Uslu S, Demirustu C, Aral E, Husnu Can Baser K. Effects of carvacrol on defects of ischemia-reperfusion in the rat liver. Phytomedicine. 2008 Jan. De Vincenzia M et al. Constituents of aromatic plants: carvacrol. Fitoterapia 2004; 75(7-8): 801-804. Force M et al. Inhibition of enteric parasites by emulsified oil of oregano in vivo. Phytother Res. 2000 May;14(3):213-4. Lambert RJ, Skandamis PN, Coote PJ, Nychas GJ. A study of the minimum inhibitory concentration and mode of action of oregano essential oil, thymol and carvacrol. J Appl Microbiol. 2001 Sep;91(3):453-62. Nostro A, Roccaro AS, Bisignano G, Marino A, Cannatelli MA, Pizzimenti FC, Cioni PL, Procopio F, Blanco AR. Effects of oregano, carvacrol and thymol on Staphylococcus aureus and Staphylococcus epidermidis biofilms. J Med Microbiol. 2007;56(Pt 4):519-23. Nostro A et al. Susceptibility of methicillin-resistant staphylococci to oregano essential oil, carvacrol and thymol. FEMS Microbiol Lett. 2004;230(2):191-5. Salgueiro LR et al. Chemical composition and antifungal activity of the essential oil of Origanum virens on Candida species. Planta Med. 2003 Sep;69(9):871-4. Santoyo S, Cavero S, Jaime L, Ibañez E, Señoráns FJ, Reglero G. Supercritical carbon dioxide extraction of compounds with antimicrobial activity from Origanum vulgare L.: determination of optimal extraction parameters. J Food Prot. 2006;69(2):369-75. Uyanoglu M, Canbed M, Aral E, Husnu Can Baser K. Effects of carvacrol upon the liver of rats undergoing partial hepatectomy. Phytomedicine 2008; 15(3): 226-9. ihpSept10_NAHS_Ad.indd 2 058.IHP NAHS mono.indd 1

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industry news A world first: Douglas Institute researchers identify neural circuits of REM sleep

A team of scientists led by Dr. Antoine Adamantidis, a researcher at the Douglas Mental Health University Institute and an assistant professor at McGill University, has released the findings from their latest study, which will appear in the October issue of the prestigious scientific journal Nature Neuroscience. Previous studies had established an association between the activity of certain types of neurons and the phase of sleep known as REM (rapid eye movement). Researchers on the team of Dr. Antoine Adamantidis identified, for the first time, a precise causal link between neuronal activity in the lateral hypothalamus (LH) and the state of REM sleep. Using optogenetics, they were able to induce REM sleep in mice and modulate the duration of this sleep phase by activating the neuronal network in this area of the brain. This achievement is an important contribution to the understanding of sleep mechanisms in the brains of mammals, as well as the underlying neuronal network, which is still not well understood despite recent breakthroughs in neuroscience. “These research findings could help us better grasp how the brain controls sleep and better understand the role of sleep in humans. These results could also lead to new therapeutic strategies to treat sleep disorders along with associated neuropsychiatric problems,” stated Dr. Antoine Adamantidis, who is also the Canada Research Chair in Neural Circuits and Optogenetics.

2013 Dr. Rogers Prize awarded to Dr. Sunita Vohra, University of Alberta

The 2013 Dr. Rogers Prize for Excellence in Complementary and Alternative Medicine was awarded to Dr. Sunita Vohra of theUniversity of Alberta at a gala award dinner in Vancouver, BC. Dr. Vohra is the founding Director of Canada’s first academic pediatric integrative medicine program, CARE (Complementary and Alternative Research and Education), at theUniversity of Alberta. She is currently evaluating the effectiveness and cost effectiveness of pediatric integrative medicine as an adjunct to usual care at the Stollery Children’s Hospital in Edmonton. She has led many high quality studies of the effectiveness of CAM including ginseng for pediatric upper respiratory tract infection and Mind Body Stress Reduction for at risk youth. With her background in pediatrics, clinical epidemiology and clinical pharmacology, Dr. Vohra is a respected leader in both CAM and conventional medicine, often working to help these two communities connect. She founded Canada’s national pediatric CAM network as well as helped found and now chairs the American Academy of Pediatrics’ Section on Integrative Medicine. Dr. Vohra initiated the use of N-of-1 studies (a multiple cross over trial performed in a single person) as an innovative and patient-centered solution to the limitations of randomized controlled trials for individualized therapies. At the beginning of her career, at the Hospital for Sick Children in Toronto, she recognized the importance of complementary and alternative medicine to her patients and their families and the lack of substantive information on the therapies and potential interactions with conventional care. She was recruited to the University of Alberta to implement her vision of the CARE program in 2003, a program which now trains the next generation of researchers, educators, and clinicians about pediatric integrative medicine. Founded in 2007, the $250,000 Dr. Rogers Prize for Excellence in Complementary and Alternative Medicine highlights the important contributions of complementary and alternative medicine to health care. Funded by Vancouver’s Lotte and John Hecht Memorial Foundation, the Prize is awarded every two years and is the largest of its kind in North America.

Canadian adults are sleep-deprived, new survey shows

Working Canadians average less than eight hours of sleep each night, are tired and unproductive on the job. A new Canadian survey from Breathe Right®Nasal Strips reveals ninety per cent of adults have experienced a poor night’s sleep, and nearly 40 per cent of survey respondents report they generally do not get a good night’s sleep. Adults ages 35-64, typically in the prime of their careers, are most likely to average less than six hours of sleep per night. The result is a tired, unmotivated, unproductive workforce that is willing to give up evening entertainment, sex, vacations days - and even a raise - just to get a good night’s sleep.

Vitality launches new line of natural health products

Vitality Products Inc. is pleased to announce the revitalization of one of Canada’s oldest natural health companies with the launch of Vitality’s new line of vitamins and supplements. The Company, a manufacturer and marketer of premium quality natural health products, has formulated, branded and launched four products in key growth categories: multivitamins, digestion, stress and sleep. The four unique products announced are Vitality introduces: Vitality® Time Release Super Multi+™, Vitality® Time Release B Complete + C™, Vitality® Digest+™ and Vitality® Relax+™. All four products are non-GMO (contain no genetically modified organisms), gluten-free, soy-free and vegan friendly. Vitality named the four products by their benefits to help retailers and consumers understand the products and added QR codes on labels to direct consumers online for additional product information. Vitality’s new branding, products and product information are available at the Company’s website: www.vitality.ca.

November / December 2013 l www.ihpmagazine.com 23

calendar DECEMBER Dec 2 & Dec 3 Biopuncture with Complex Homeopathics Organized by: Pascoe Toronto, ON For more information, visit http:// www.pascoecanada.com December 5-8 FirstLine Therapy Certification Organized by: Metagenics Austin, TX For more information, please visit http://www.metagenics.com

JANUARY

JANUARY 16 Family Medicine Grand Rounds Organized by: CFPC Edmonton, AB For more information, visit http:// www.cfpc.ca/UpcomingEvents/ January 22 Lessons from the Canadian Hypertension Guidelines Organized by: CFPC Toronto, ON For more information, visit http:// www.cfpc.ca/UpcomingEvents/

December 7 Ultimate Sports Nutrition Seminar Series Organized by: Metagenics Pittsburg, PA For more information, please visit http://www.metagenics.com

January 25 Family Medicine Clinic Day Organized by: CFPC Toronto, ON For more information, visit http:// www.cfpc.ca/UpcomingEvents/

December 11 Phytotherapy, Oligo-Elements, Plexes Organized by: Seroyal Teleconference For more information, please visit http://www.seroyalseminars.com

February 8-11 Canadian Digestive Diseases Week 2014 Organized by: CASL Toronto, ON For more information, visit cag-acg. org/cddw

December 18 Integrating Bio-Identical Hormones and Herbs for Menopausal Therapy Organized by: AARM Online Webinar For more information, visit http:// restorativemedicine.org/cme-webinars/ December 22 Atopic Dermatitis Organized by: CFPC Vancouver, BC For more information, visit http:// www.cfpc.ca/UpcomingEvents/ December 27-29 Primary Care Dermatology Organized by: MCE Conferences New York City, NY For more information, visit http:// www.mceconferences.com/medicalconferences.php

FEBRUARY

February 14-16 Primary Care Office Orthopedics and Sports Medicine Organized by: MCE Conferences Park City, Utah For more information, visit http:// www.mceconferences.com/medicalconferences.php February 20-22 2014 Scientific Meeting of the Canadian Pediatric Endocrine Group Organized by: UBC Montreal, QC For more information, visit interprofessional.ubc.ca/CPEG2014 February 25-March 1 2014 Scientific Conference of the Canadian Spine Society Organized by: Spine Canada Lake Louise, AB For more information, visit spinecanada.ca

24 www.ihpmagazine.com l November / December 2013

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

MARCH

March 7 Assessment & Management of the Patient with Complex Chronic Pain 2014 Organized by: CFPC Vancouver, BC For more information, visit http:// www.cfpc.ca/UpcomingEvents/ March 27 LEAP (Learning Essential Approaches to Palliative and End-of-Life Care) Organized by: CFPC Bathurst, NB For more information, visit http:// www.cfpc.ca/UpcomingEvents/

APRIL

April 10-14 CHFA West Conference Organized by: CHFA Vancouver, BC For more information, please visit: https://www.chfa.ca/tradeshows/ April 24-26 2014 Canadian Respiratory Conference Organized by: Canadian Lung Association Calgary, AB For more information, visit lung.ca/ crc/home-accueil_e.php April 25-29 Canadian Conference on Medical Education Organized by: CCME Ottawa, ON For more information, visit mededconference.ca/ccme2014/

Make a smart choice

Carlson Norwegian Fish Oils As we age, it becomes increasingly important to protect the health of our hearts. Managing stress levels, eating well, and staying active are all important lifestyle factors that contribute to overall cardiovascular health. Taking Carlson award-winning Norwegian fish oils as part of your daily routine is another way that you can help support your cardiovascular system. Carlson Norwegian fish oils provide the important omega-3s, EPA & DHA. Current scientific research suggests EPA & DHA are important and promote cardiovascular and brain health. Carlson fish oils are renowned for their purity and great taste.

Choose Quality. Choose Carlson.

888-234-5656 | www.carlsonlabs.com

Product MonograPh Carlson Norwegian Cod Liver Oil Carlson Norwegian Cod Liver Oil provides EPA and DHA, two very long- chain polyunsaturated omega-3 fatty acids found in fish. The oil also provides naturally occurring vitamin D and preformed vitamin A. EPA and DHA have been the topic of over 12000 published, peer-reviewed journal articles. Clinical intervention studies have shown a wide array of potenial physiological benefits from EPA and DHA consumption, notably improved cardiovascular health, improved mood and well-being, support of fetal development, delay of cachexia associated with cancer and AIDS, and others. Impact to cardiovascular health is the most publicized benefit of EPA and DHA consumption. The single most important outcome delivered by EPA and DHA appears to be their ability to reduce risk of sudden coronary death (SCD), with estimates as high as a 45% reduction in SCD risk among patients whom had recently survived a heart attack (Marchioli 2002). In this large, “megatrial” of EPA and DHA supplementation, 850mg of combined EPA and DHA per day for two years achieved a 45% reduction in SCD risk as well as a 25% reduced risk of all-cause mortality. It has been suggested that as little as 250mg per day of combined EPA and DHA are sufficient to achieve the very profound impact to SCD risk described above (Mozaffarian 2006). Other experts believe a dosage of 600-900mg of combined EPA and DHA per day is required to achieve this outcome (KrisEtherton 2003). While low dosages of EPA and DHA appear to deliver a large magnitude of benefit to SCD risk and subsequent risk of all-cause mortality, there appears to be added benefit in consuming larger dosages (Mozaffarian 2007). At a dosage range of 2000-4000mg of combined EPA and DHA per day, benefit to cholesterol levels is achieved, an outcome not delivered at the lower dosages described above. When consumed at this larger dosage range, EPA and DHA powerfully reduce fasting triglyceride levels (20-45%) while simultaneously achieving increases to HDL-C levels of 5-15% (Harris 1997). LDL-C levels are typically unchanged, but may increase 5-10% (Harris 1997). In a large intervention trial spanning five years, large dosages of EPA (1800mg per day) were supplemented to a Japanese population, estimated to be consuming a mean of 900mg of EPA and DHA per day through diet alone. While mechanistic detail remains speculative, the trial reported a 19-28% reduced risk of non-fatal major coronary events among EPA supplemented subjects (Yokoyama 2007). Therefore, while low-dose EPA and DHA have been reproducibly demonstrated to reduce SCD risk, this large landmark study highlights that at higher dosages, EPA and DHA begin to reduce risk of non-fatal cardiovascular events (Mozaffarian 2007, Yokoyama 2007).

Carlson Norwegian Cod Liver Oil – Supplement Facts Serving size 1 teaspoon (5ml)

amount per teaspoon

Calories

Vitamin A

850 IU

Vitamin D

400 IU

Vitamin E

10 IU

Omega-3 fatty acids DHA (docosahexaenoic acid) EPA (eicosapentaenoic acid) ALA (alpha linolenic acid)

1100 mg 500 mg 400 mg 40 mg

References Harris WS. n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997 May;65(5 Suppl):1645S-1654S. Kris-Etherton PM, Harris WS, Appel LJ; AHA Nutrition Committee. American Heart Association. Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association. Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):151-2. Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R, Franzosi MG, Geraci E, Levantesi G, Maggioni AP, Mantini L, Marfisi RM, Mastrogiuseppe G, Mininni N, Nicolosi GL, Santini M, Schweiger C, Tavazzi L, Tognoni G, Tucci C, Valagussa F; GISSI-Prevenzione Investigators. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione. Circulation. 2002 Apr 23;105(16):1897-903. Mozaffarian D. JELIS, fish oil, and cardiac events. Lancet. 2007 Mar 31;369(9567):1062-3. Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA. 2006 Oct 18;296(15):1885-99. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007 Mar 31;369(9567):1090-8.

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product profiles

Legend

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EnergyNOx Contains Panax ginseng enhanced with a natural source of supplemental nitric oxide (NO). Panax ginseng is a restorative and an adaptogen that reduces exercise-induced muscle damage and increases NO production and activity in blood vessel walls. NO is produced in the body from consumed nitrates and nitrites and supports energy levels.

ColdNOx Contains Andrographis paniculata enhanced with a natural source of supplemental nitric oxide (NO). Andrographis paniculata supports the immune system and is an excellent cold and flu remedy. NO acts as an anti-microbial and improves blood flow, bringing immune factors to the site of infection to speed up recovery.

An unbeatable one-two punch The critical role that plant foods play in our diet cannot be overstated. Yet very few of us consume the recommended number of daily servings. Thanks to PhytoBerry Multi and VegeGreens Multi, that mission just got a whole lot easier. Combined, they provide all your fruits, all your veggies and all your vitamins & minerals in just 2 little scoops!

Cyto-Matrix - Omega-D3 Liquide Forte

Carlson Norwegian Cod Liver Oil Carlson Norwegian Cod Liver Oil provides important omega-3s EPA & DHA, essential nutrients that support the health of our brain and vision and promote the maintenance of overall good health. 888-234-5656 www.carlsonlabs.com

Evidence based dosages for all indications; High safety profile; Molecularly distilled, ultra-pure fish oil; East to administer for maximum patient adherence; No fishy aftertaste, light citrus flavour. Each teaspoon (5mls) contains: Fish Oil Concentrate 4,377 mg; Omega-3 Fatty Acids - 2,845 mg, EPA (Eicosapentaenoic acid) - 1,750 mg; DHA (Docosahexaenoic acid) - 875 mg; Vitamin D3- 1000 IU. November / December 2013 l www.ihpmagazine.com 27

product profiles

Legend

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

ViraClear EPs 7630™ - Clinically-Proven Extract Viraclear EPs 7630™ contains a proprietary extract, obtained from the roots of the Pelargonium sidoides plant, an herb long used to treat cough and respiratory ailments. It works differently, unlike conventional remedies that simply mask symptoms, Viraclear EPs 7630™ addresses the cause to help speed recovery and shorten the duration of upper respiratory tract infections. For more information please call 1.800.644.3211 or visit www.integrativeinc.com

greens+ whole body NUTRITION A revolution in achieving complete, whole body nourishment with the power of advanced food fermentation and the alkalizing and energizing benefits of greens+ O! 100% vegan, gluten-free, dairyfree, soy-free and made with non-GMO ingredients, greens+ whole body NUTRITION harnesses the power of supercharged whole food ingredients and fermentation to optimize key body systems nourishing and balancing your whole body!

omega3+ joy Omega-3 fatty acids are integral to our health and wellbeing – and have a major part to play in our mental health and happiness! Based on leading research and developed in-conjunction with a naturopathic doctor, omega3+ joy contains EPA concentrate, an essential Omega-3 fatty acid clinically proven to help improve mood and mental outlook, including the seasonal blues, as well as reduce inflammation in the body.

Metagenics Launches PhytoMultiTM Capsules Metagenics now offers PhytoMulti in easy-to-swallow vegetarian capsules. PhytoMulti is an entirely new class of daily foundation supplementation designed to help defy aging. This unique product defends cells from free radical damage and oxidative stress, recharges cellular health, and nourishes cells with a complex array of phytonutrients. PhytoMulti is the only multivitamin/mineral supplement providing a research-based, broad spectrum of phytonutrients and plant extracts scientifically tested for antioxidant protection and DNA stability potential. PhytoMulti is also available in tablet form. * These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Metagenics.com • 800.692.9400 US • 800.268.6200 Canada

28 www.ihpmagazine.com l November / December 2013

product profiles

Legend

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

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

PASCOFEMIN®

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

PASCOFEMIN® is a well-tolerated, effective solution for physical and emotional symptoms of menopause such as hot flashes, headaches, mood swings and sleep disturbances. In one study of women who had tried other therapies to control menopause symptoms without success, significant effectiveness was found in 71% of patients. Even more impressive, after patients left the study and had to purchase it on their own, 80% were satisfied enough to continue using PASCOFEMIN®. There are no known side effects or contraindications.

GABA 700 GABA 700 helps to temporarily promote relaxation and helps to temporarily reduce symptoms associated with acute psychological stress.(1) Provides 700 mg of gamma-aminobutyric acid in a dairy-free, gluten-free, vegan formula. 1. Gamma-aminobutyric acid (GABA), Monograph. Altern Med Rev. 2007 Sep;12(3):274-9.

DIM DIM helps in reducing recurrent breast pain (cyclical mastalgia) and promotes healthy estrogen metabolism in pre menopausal women.(1) Provides 75 mg of 3,3’ -diindolylmethane per day in a dairy-free, gluten-free, vegan formula. 1. Zeligs MA, Brownstone PK, Sharp ME, Westerlind KC, Wilson SM, John SM (2005). Managing cyclical mastalgia with absorbable diindolylmethane: A randomized, placebo-controlled trial. JANA 8(1): 10-20 November / December 2013 l www.ihpmagazine.com 29

30 www.ihpmagazine.com l October 2013

cover story

The Vivian Medical Spa by Philip Rouchotas, Msc, ND photographs by Samantha Noakes

The Vivian Medical Spa is a stunning integrative medical facility and European-inspired spa situated 30 minutes northeast of Toronto, in a beautiful home overlooking a 25-acre property. The center offers preventative therapy, anti-aging medical treatments and non-surgical cosmetic aesthetics designed to rejuvenate and optimize health. The medical facility was founded in 2005 by Dr. Andrew Wojcicki MD, whose medical background prior to establishing this center was in orthopedic surgery, internal medicine, gerontology and anti-aging medicine. Dr. Andrew’s wife, Dr. Anna Wojcicka MD, and a team of healthcare professionals work together to customize individual care for their patients and support them in healthy lifestyle change in order to prevent illness and enhance quality of life.

Dr. Andrew Wojcicki, MD Therapies offered at the facility include bioidentical hormone replacement, detoxification programs, intravenous therapies, non-surgical joint rejuvenation using hyaluronic acid injection therapy and platelet rich plasma (PRP), back decompression therapy, and cold laser. In addition, the center offers a range of physical activities including hiking on its stunning grounds and the use of exercise equipment. Aesthetic therapies offered include botox, fillers, Juvederm, and Lipolaser. Cold laser is a key feature of chronic pain management, while Lipolaser is a cosmetic laser that enhances fat loss and reduction of cellulite. Detoxification techniques used include Moor mud bath therapy, salt water pools, and infrared sauna. Balnotherapy refers to “bath therapy”, considered to be distinct from hydrotherapy, using a variety of organic solutions or “mud” that contains humic acid, minerals, phytohormones, and other organic substances. More specifically, a recent systematic review defines balnotherapy as “the use of baths containing thermal mineral waters from natural springs at a temperature of November / December 2013 l www.ihpmagazine.com 31

32 www.ihpmagazine.com l October 2013

cover story at least 20 °C and with a mineral content of at least 1 g/L” (Falagas 2009). At the centre, a typical bath consists of half an hour at 42 °C, based on the physics of the solute. Austrian mud is used for the treatment of pelvic inflammatory disease (PID) as well as prostate disease, for instance. Intravenous therapies include intravenous vitamin C for a range of conditions including adjuvant cancer therapy. For cancer, Dr Wojcicki also utilizes intravenous bicarbonate (HCO3) alongside IVC in in his practice. Dr Wojcicki emphasizes that the facility employs a truly holistic approach in treating patients with cancer. In addition to intravenous therapies, his patients receive counseling regarding diet, with a reduction in refined carbohydrates and an increase in fruits and vegetables recommended as part of an alkalinizing diet. In addition to cancer, Dr Wojcicki uses IVC therapy for patients suffering from fibromyalgia and arthritis, for patients with neurodegenerative disease such as dementia and Parkinsons, as well as in the prevention and treatment of bacterial and viral infections. For patients with atherosclerosis, intravenous EDTA is used alongside IV phosphatidylcholine (PC). Plaque therapy is the use of essential phospholipids (EPL) extracted from soy. This may be recommended for patients who have suffered a stroke, poor cardiac function, or who have diabetes. Anticipated outcomes from an 10-week program include a reduction in atherosclerotic plaques between 10-60%, reduction in angina pain and frequency, reduction in LDL cholesterol, increase in HDL cholesterol, improvement in cognitive function, improvements in sexual function, and improved exercise tolerance as measured by walking distance. Not unlike a growing number of his colleagues, Dr Wojcicki questions the real usefulness of statins in their role as the universally applied therapy in most conventional medical practices, especially apart from a proper emphasis on the role of diet and lifestyle. IV therapies for liver support include N-acetylcysteine (NAC), glutathione, and phosphatidylcholine (PC).

Dr Wojcicki’s story is an intriguing one: originally an MD in Poland, licensed in 1988, Dr Wojcicki practiced as an orthopedic surgeon for several years prior to immigrating to Canada. At that time, he completed re-training through the University of Toronto and completed a five-year residency in internal medicine and gerontology. He established a private practice in 1996, and became increasingly more interested in a more holistic approach. In particular, he felt dissatisfied with the constraints of medical guidelines, convinced that he should be free to “use my own brain.” Dr Wojcicki believes that the therapeutic application of medicines is all about their mechanism of action and “knowing the molecule”; if you have the biochemical basis for its behaviour, you can apply it intelligently in human systems. Dr Wojcicki expresses reservations about the pharmaceutical bent present within medicine as it is commonly practiced. He dislikes the mentality that focuses on pharmaceutical drugs first and relegates diet and lifestyle to a secondary role. Treatment and prevention of disease begins with lifestyle, he says, and this is systematically neglected in primary medical care. This is especially problematic in the management of conditions such as obesity and diabetes. Dr Wojcicki relates that he often recommends a gluten and/ or dairy free diet and the avoidance of genetically modified organisms (GMOs), in patients with asthma, allergy, or gastrointestinal problems. An initial visit with Dr Wojcicki lasts two hours and includes a one hour discussion of lifestyle and diet, as well as a physical exam and thoracic ultrasound. Additional testing that maybe run includes hair heavy metal testing, salivary and blood hormone testing, cancer markers, cardiovascular biomarkers such as ApoB and E, hs-CRP, homocysteine, fibrinogen, and a calculation of the Framingham risk score. The patient receives a medical report regarding current health status and recommendations based on diet, lifestyle, supplements, and hormones. A referral to a specialist is given where indicated.

Photo top left: From left to right: Dr. Andrew Wojciki, MD, Brandy Kinner, Sheila Sanchez Silverio, Krystyna Mlodzianowska, Carly Andrews

November / December 2013 l www.ihpmagazine.com 33

34 www.ihpmagazine.com l October 2013

cover story

Dr Wojcicki retains one foot in the conventional model, so to speak. His wife remains as a full time hospitalist at Southlake Hospital (Newmarket, Ontario), and enjoys ongoing involvement there given her own surgical background.

References Falagas ME, Zarkadoulia E, Rafailidis PI. The therapeutic effect of balneotherapy: evaluation of the evidence from randomised controlled trials. Int J Clin Pract. 2009 Jul;63(7):1068-84.

The facility is open to both membership service and walk-in patients. The membership delivers walk-in service for almost free. Walk-in service is based on fee-for-service, with some testing covered by OHIP. Dr Wojcicki estimates that about 20% of his practice is management of chronic disease, while 80% focuses on disease prevention and wellness.

Andrew Wojciki, MD : Chief Medical Officer

IHP is grateful to Dr Wojciki and the Vivian Medical Spa team for taking the time to introduce us to their impressive facility. Dr Wojciki embodies the true tenants of integrative, holistic, individualized medicine. He serves as a powerful force in the advancement of integrative therapeutics, and his choice of facility marries perfectly with his vision of world-class healthcare.

Brandy Kinner: Director Sheila Sanchez Silverio, MSc: Clinic Manager Krystyna Mlodzianowska: Medical Assistant Carly Andrews: Reception Tetyana Nakonechna: Aesthetician

November / December 2013 l www.ihpmagazine.com 35

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$ 4 , ' > 8 9 : ? + , "( )@*) '-? ' ! ' " NHPD Monograph. Health Canada. Updated January 2008. http:// References + 1 Lysine. 4 A , (!"*3-?,!3 " Accessed Bellati U, Liberati M. Minerva Med. Jun;85(6):327-32. 5 A> 2& 4. 1994 4> . ;> % webprod.hc-sc.gc.ca/nhpid-bdipsn/monoReq.do?id=134&lang=eng.

February 2013. Civitelli R, Villareal DT, Agnusdei D, et al. Nutrition. 1992 Nov-Dec;8(6):400-5. > % , McBeath ! 2 (B!*3-?"@3 , M, Pauling L.Journal of Orthomolecular Medicine 1993;8(2): 77-8. Colella G,% Cannavale R, Vicidomini A, et al.Int ImmunopatholPharmacol. . A %2 #

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2010 % 4 :: + 45 4 + # %A $ McCune MA, Perry HO, Muller SA, et al. Cutis. 1984 Oct;34(4):366-73. PubMed Jan-Mar;23(1):143-51. 2 2 PMID: 6435961. > Favia G, Mariggio MA, Maiorano F, et al. J BiolRegulHomeost Agents. 2008 Apr, )(@ *4 "-?@!B ,3 Milman N, Scheibel J, Jessen O. ActaDermVenereol. 1980;60(1):85-7. PubMed Jun;22(2):109-16. PMID: . % 2 6153847. +$ 2 Gaby A. Lysine. Nutritional Medicine. Concord: Fritz Publishing. 2011: 187. Nusgens BV, Humbert P, Rougier A, et al.Eur J Dermatol. 2002 Jul 5 , "(,3 *,-?!B! @ Griffith RS, Walsh DE, Myrmel KH, et al. Dermatologica. 1987;175(4):183-90. Aug;12(4):XXXII-XXXIV. 2 5A3115841.

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clinic profile

The Community Clinic Roncesvalles Successfully F Providing Equal Access To Care By Philip Rouchotas, MSc, ND Photographs by Bruce Redstone

rom the beginning of his practice in 2008, Dr. Chris Pickrell, ND, RH decided that he wanted to offer health services at rates that were affordable and accessible. He set out to build his practice in accordance with that plan and decided this by literally writing out the answer to the question: “What does integrity mean to me?” The answer to this question dictated how he would practice, and he made a personal commitment never to operate his business from a place of fear, but rather to only operate from a place where he felt comfortable and displayed integrity. At this point, Dr. Pickrell started his private practice and teamed up with an acupuncturist to create the community

38 www.ihpmagazine.com l November / December 2013

acupuncture clinic. He decided on the clinic location because he lived in the neighbourhood and the location matched his philosophy on healthcare. He knew other NDs had worked in that location and had moved on, but he was determined and became successful. The clinic consists of one large room from which the clinic offers all its services. He currently sees over 50 patients per week. In 2012, Dr. Pickrell teamed up with two other clinics to continue his journey of providing affordable and accessible care. The result was the creation of a team of three NDs as a board of directors for The Community Clinic. Together, they share branding, philosophy of practice, resources, and even practitioners. The

clinic profile mandate of The Community Clinic remains to provide a better model of naturopathic care in Ontario, one that is more accessible to patients and also financially successful for the practitioners. Dr. Pickrell offers naturopathic services, acupuncture, yoga, and educational talks. All of these fall under the umbrella of The Community Clinic Roncesvalles. To help further the clinic’s goals, the business model moves towards the idea of “filling more spaces more often”. In other words, the patient experience is similar to that of other conventional practitioners: combining scheduled visits with the flexibility of walk-in access. From a business perspective, filling space with a patient, even if it’s a smaller source of revenue, is better than allowing the space to be fallow, obtaining no revenue at all. Dr. Pickrell has found that less than 20% of Ontarians have the coverage or the income available for most naturopathic care, so a large amount of the population cannot access services. From a business perspective, this means the majority of the market is untapped. Regardless of the service they wish to access, Dr. Pickrell’s patients always have the option of choosing to pay what matches them best. Every service has the option to “pay what you can” or “pay as you like”. When asked if everyone simply chooses to pay the lower rate, Dr. Pickrell responds: “Not at all. Time and again the people who can afford it or have coverage pay on the higher end. Others have started on the lower rate and have chosen to move up to the higher rates as their situations changed.” Approximately half of his patients access the half-rates and only a handful of people have elected not to pay at all, though everyone receives the option. A few people actually barter. When asked further about this, Dr. Pickrell recounts an experience where one of his patients asked if she could pay with chicken because her parents owned a

chicken farm. He replied humorously: “I’ve been waiting my whole life for someone to pay me with a chicken.” Dr. Pickrell’s educational talks include a group elimination diet exercise, as well as talks to understand digestion and absorption, with planned talks on fertility. All talks are free of charge. At any given time, 20% of the community acupuncture patients (which sees the higher volume of people) are also seeing him as an ND. Most yoga students also overlap with the other health services. Dr. Pickrell has everything set-up such that it is easy to flow between services, with no additional forms or fees to move between them and there are no late fees, cancellation fees, or additional first visit fees. Many of the patients he sees tend to use The Community Clinic services as their primary care access, opting to use the acupuncture clinic or walk-in clinic components for acute concerns. When asked about the brands and supplements he carries, Dr. Pickrell explains that he doesn’t carry many supplements. Many of his patients see

him for counselling. When further prescriptions are required, Dr. Pickrell relies on herbs and herbal tinctures. Over time, he found that herbal tinctures were difficult for patients to purchase because they were so expensive. Going back to his plan to provide accessible and affordable services and using his expertise as a Registered Herbalist, Dr. Pickrell started a herbal tincture company called ‘Perfect Herbs’. His herbal company not only supplies his patients, but he also sells these tinctures to other clinics, so that they too may benefit from the decreased cost. Perfect Herbs now carries over 120 individual tinctures and a dozen signature blends. Dr. Pickrell has had surprisingly few obstacles in his career. His practice has built up smoothly, despite minimal marketing. He believes the quality of care is what has driven his current patient base, since the majority of his patients come from word-of-mouth referrals from existing patients. He is well-known in his community, and comes up as one of the first few hits on Google for the search “affordable ND”. His average patient demographic is

November / December 2013 l www.ihpmagazine.com 39

clinic profile

adults in the 24 to 44 age range, but also many over the age of 70. In general, they are people who want to see an ND and with a genuine desire to improve their health and live better. Commonly, Dr. Pickrell’s patients tell him “thank you for offering this model of care, otherwise I wouldn’t be able to afford it.” To date, The Community Clinic is needle-stick free, which is impressive considering more than 10,000 acupuncture needles have been inserted. Recently, Dr. Pickrell has teamed up with Dr. Jon Sheridan, ND, who now also offers his services at the clinic within the same framework. Together, they would like to thank the community for supporting the philosophy of accessibility. Their future directions include expanding the number of practitioners who are using this model, and at some point perhaps opening the first walk-in naturopathic clinic. We at IHP wish these awe-inspiring practitioners continued success. The Community Clinic Roncesvalles Operating From The Herbal Clinic & Dispensary 409 Roncesvalles Ave. Toronto, ON Phone: 416-436-3715 Email: roncesvalles@thecommunityclinic.ca Website: http://www.thecommunityclinic.ca

40 www.ihpmagazine.com l November / December 2013

clinic profile

October 2013 l www.ihpmagazine.com 45

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The Mediterranean diet is associated with markedly lower risk of several chronic diseases, including cardiovascular disease and diabetes (Eustruch 2006, Interact Consortium 2011, Nordmann 2011), and a high fruit and vegetable diet has been shown to reduce risk of cancer (Block 1992), in large part due to high amounts of combined phytonutrients. Phytonutrients have been shown to confer beneficial health effects through numerous mechanisms, including modulation of signal transduction pathways, antioxidant properties, and through hormonal effects. PhytoMulti contains over 20 of these plant substances, including: lutein, zeaxanthin, acacia nilotica, and extracts of artichoke leaf, grape seed extract, green coffee, green tea, citrus bioflavonoids, resveratrol, prune skin, watercress, rosemary, pomegranate, lycopene, cinnamon, bitter melon, and blueberry. Multivitamin supplementation has been shown to benefit a variety of physical and cognitive parameters particularly in children, pregnant women or women who may become pregnant, individuals under increased stress, individuals with poor absorption, and the elderly. In pregnancy, supplementation with a folic acid containing multivitamin has been shown to reduce risk of complications such as placental abruption, preeclampsia, in addition to decreasing risk of congenital defects including neural tube defects, anencephaly, myelomeningocele, meningocele, oral facial cleft, structural heart defects, limb defects, urinary tract anomaly, and hydrocephalus when used prior to conception and during the first trimester (Wilson 2007). Periconceptional multivitamin use in lean women has been shown to decrease the risk of small-for-gestational-age (SGA) under the 5th percentile by up to 46% compared to non-users (OR=0.54, 95% CI), and has been associated with a 71% reduction in preeclampsia risk (OR=0.29, 95% CI) in lean women, users versus non-users (Catov 2007; Bodnar 2006). Periconceptional multivitamin use has also been associated with reduced risk of several pediatric cancers, including leukemia (OR=0.61) (39% reduced risk); pediatric brain tumors (OR=0.73) (27% reduced risk); and neuroblastoma (OR=0.53) (47% reduced risk) in a recent metaanalysis (Goh 2007). In patients under high levels of psychological stress, use of a multivitamin has been shown improve perceived levels of stress and psychometric parameters. Gruenwald et al (2002) found that use of a multivitamin for 6 months resulted in a 40.7% overall improvement in self rated stress levels using a psychologicalneurological questionnaire to assess “psycho-organic, central vegetative, and somatic discomforts.” Other outcomes included a 29% decrease in frequency of infections and 91% decrease in gastrointestinal discomfort. Schlebusch et al (2000) found similar benefit on various psychometric parameters in a 30 day trial (1997), and Harris found that multivitamin supplementation can improve measures of mood, stress, and alertness in older men (2011). Importantly, supplementation with a spectrum of B vitamins has also been shown to reduce ratings of workplace stress (Stough 2011). Several trials have shown increased cognitive performance in children taking a multivitamin supplement. Benton et al (1988) found a significant increase in nonverbal intelligence in children taking a multi versus those taking placebo after 8 months’ intervention. In a 14 month study of 608 children, Vazir et al (2006) found a significant increase in attention-concentration increment scores in those supplemented with a micronutrient-fortified beverage versus those receiving placebo. Additional benefits demonstrated in children include a reduced mean duration (5.0 versus 7.5 days, supplement versus placebo) of several common childhood illnesses including such as fever, cough and cold, diarrhea, and ear infections (Sarma 2006). In the elderly, multivitamin supplementation has been shown to significantly improve status of such nutrients as vitamin D, vitamin B6, vitamin B12, folate, vitamin C, vitamin E, zinc, and selenium (McKay 2000; Girodon 1997). In addition, supplementation has also been found to significantly reduce rates of infection in the elderly, as found a trial in 81 subjects given various supplemental combinations of micronutrients and followed over a 2 year period (Girodon 1997).

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References Benton D, Roberts G. Lancet. 1988 Jan 23;1(8578):140-3. Block G, et al. Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutrition and cancer 1992;18(1):1-29. Bodnar LM, Tang G, Ness RB, Harger G, Roberts JM. Am J Epidemiol. 2006 Sep 1;164(5):470-7. Epub 2006 Jun 13. Catov JM, Bodnar LM, Ness RB, Markovic N, Roberts JM. Am J Epidemiol. 2007 Aug 1;166(3):296-303. Epub 2007 May 11. Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Fertil Steril. 2008 Mar;89(3):668-76. Epub 2007 Jul 10. Eustruch R, Martínez-González MA, Corella D, et al. Ann Intern Med. 2006 Jul 4;145(1):1-11 Girodon F, Lombard M, Galan P, Brunet-Lecomte P, Monget AL, Arnaud J, Preziosi P, Hercberg S. Ann Nutr Metab. 1997;41(2):98-107. Goh YI, Bollano E, Einarson TR, Koren G. Clin Pharmacol Ther. 2007 May;81(5):685-91. Epub 2007 Feb 21. Grieger JA, Nowson CA, Jarman HF, Malon R, Ackland LM. Eur J Clin Nutr. 2007 Nov 28. Gruenwald J, Graubaum HJ, Harde A. Adv Ther. 2002 May-Jun;19(3):141-50. Harris E, Kirk J, Rowsell R, Vitetta L, Sali A, Scholey AB, Pipingas A. Hum Psychopharmacol. 2011 Dec;26(8):560-7. InterAct Consortium. Diabetes Care. 2011 Sep;34(9):1913-8. McKay DL, Perrone G, Rasmussen H, Dallal G, Hartman W, Cao G, Prior RL, Roubenoff R, Blumberg JB. J Am Coll Nutr. 2000 Oct;19(5):613-21. Murphy MM, et al. Journal of the American Dietetic Association 2011:in press. Nilsen RM, Vollset SE, Rasmussen SA, Ueland PM, Daltveit AK. Am J Epidemiol. 2008 Apr 1;167(7):867-74. Epub 2008 Jan 10. Nordmann AJ, Suter-Zimmermann K, Bucher HC, et al. Am J Med. 2011 Sep;124(9):841-51.e2. Ribeiro ML, Arçari DP, Squassoni AC, Pedrazzoli J Jr. Mech Ageing Dev. 2007 Oct;128(10):577-80. Epub 2007 Aug 15. Sarma KV, Udaykumar P, Balakrishna N, Vijayaraghavan K, Sivakumar B. Nutrition. 2006 Jan;22(1 Suppl):S8-14. Schlebusch L, Bosch BA, Polglase G, Kleinschmidt I, Pillay BJ, Cassimjee MH. S Afr Med J. 2000 Dec;90(12):1216-23. Stough C, Scholey A, Lloyd J, Spong J, Myers S, Downey LA. Hum Psychopharmacol. 2011 Oct;26(7):470-6. Tanvetyanon T, Bepler G. Cancer. 2008 Jul 1;113(1):150-7. Vazir S, Nagalla B, Thangiah V, Kamasamudram V, Bhattiprolu S. Nutrition. 2006 Jan;22(1 Suppl):S2632. Wilson RD, et al. J Obstet Gynaecol Can. 2007 Dec;29(12):1003.

The Journal of

Integrated Healthcare

Practitioners 1

C hemotherapy-related cognitive impairement 2 p62 Diabetes Medications

Strategies for intervention

by Meighan Valero, ND Be Well

Reduced risk of disease-related complications?

by William R. Ware, ND, PhD

University of Western Ontario

3 3 CE

Vitamin B12

Update on clinical applications

by Christopher Habib, ND Mahaya Forest hill

The metabolic fate of alpha linolenic acid (ALA) Extremely limited conversion efficiency By Leah Gillingham, MSc, PhD

National Fundamentals for Health

44 www.ihpmagazine.com l November / December 2013

editor’s letter

Happy Holidays

ecember is a special time of year… In theory, non- practice commitments let up a bit, yet practice becomes swamped with people looking to take advantage of their health benefits before the year’s end. Regardless of what is happening in our professional life, the Holidays provides a time to reflect on the year that was, and to spend much needed time with family and friends. IHP has had the privilege of showcasing some incredible physicians through 2013, and Dr Andrew Wojcicki, MD is no exception. Feast your eyes on perhaps the most beautiful facility we at IHP have yet to present! We also applaud Chris Pickrell for a modest, affordable, yet highly effective system of practice showcased in the issue’s clinic profile. The Journal of IHP features four incredible contributions; Dr’s Habib and McGregor update the evidence- base regarding clinical application of vitamin B12. Dr Valero introduces us to a rapidly expanding area of research likely to be new to most readers; chemotherapy- related cognitive impairment. Dr Ware continues to deliver mesmerizing critiques of pharmacotherapeutic management of chronic disease, in this case the focus questions the clinical validity of hypoglycemic medications. Lastly, we are grateful to Leah Gillingham, PhD for providing the issue’s CE article, an eloquent review of the limited conversion of alpha linolenic acid to EPA and DHA.

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

November/December 2013 l www.ihpmagazine.com 45

Integrated Healthcare

President | Olivier Felicio (416) 203-7900 ext. 6107 CEO | Cory Boiselle (416) 203-7900 ext. 6114 Controller & Operations | Melanie Seth CMO | Zinnia Crawford (416) 203-7900 ext. 6135

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46 www.ihpmagazine.com l September 2013

Berberine SAP

Science-based berberine for optimal metabolic function Berberine is an active constituent found in a variety of species of plants. Newer studies have found berberine has biological effects in several pathways in the body, indicating it may be a potential treatment for metabolic syndrome.[1] Metabolic syndrome is hypothesized as beginning with an accumulation of lipids in non-adipose tissues, known as non-alcoholic fatty liver disease (NAFLD).[1] Berberine also has studies supporting its ability to reduce symptoms associated with NAFLD, as well as showing significant antidiabetic effects and lipid-lowering capability.[2, 3, 4] Historically, berberine has been used for its antimicrobial activity, as berberine is active against a wide range of organisms including bacterial viruses, fungi, helminthes, and chlamydia.[1]

ACTIVE INGREDIENTS

Each capsule contains:

Berberine hydrochloride . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300 mg Goldenseal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 mg Contains no: Preservatives, artificial flavor or color, sugar, dairy, starch, wheat, gluten, yeast, soy, citrus, or eggs. Berberine SAP contains 90 capsules per bottle.

ADULT DOSAGE

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

INDICATIONS

ɶ Berberine SAP may be effective in reducing non-alcoholic fatty liver disease (NAFLD);

ɶ Berberine SAP may assist in regulating symptoms associated with metabolic syndrome; ɶ Berberine SAP supports healthy cholesterol and glucose levels in patients

with type-2 diabetes or hypercholesterolemia; ɶ Berberine SAP supports healthy microbial activity against bacterial, viruses, helminthes, and fungi, without having a negative impact on beneficial bacteria.

SAFETY AND SIDE EFFECTS

There is a long history of safe usage of berberine clinically. However, some adverse effects have been reported, including gastrointestinal concerns, allergic skin reactions, and arrhythmia.[1] There are some reports that indicate berberine may induce apoptosis in hepatoma cells; however, these cytotoxic effects were not seen in healthy hepatocytes.[1] In a recent study, berberine supplemented in oral dosages of 500 mg three times per day was associated with gastrointestinal symptoms in 34.5% of participants.[3] However, at the reduced dose of 300 mg of berberine three times per day, gastrointestinal side effects were eliminated while observing similar beneficial effect on glucose and lipid control. For this reason and optimal patient safety, Berberine SAP is dosed at 300 mg per capsule of berberine hydrochloride.

PURITY, CLEANLINESS AND STABILITY

All ingredients listed for each product lot of Berberine SAP have been validated by a third-party laboratory for identity, potency, and purity.

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

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

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Berberine SAP PRODUCT MONOGRAPH

Berberine is an isoquinoline alkaloid present in a variety of plant species including Hydrastis canadensis, Coptis chinensis, Berberis aquifolium, and Berberis vulgaris.[1] Historically, berberine is well-known for its use as an antimicrobial; however, more recent research has demonstrated that this alkaloid has a multitude of therapeutic applications, including metabolic diseases like obesity, metabolic syndrome, and type 2 diabetes.[1]

and type 2 diabetes, with patients also demonstrating improvement in liver function observed via a reduction in liver enzymes.[4]

Berberine metabolites become widely distributed within the body, with kinetic studies showing berberine is found in the liver, kidneys, spleen, lung, and brain. It is found in its highest concentration in the liver at about a 70-fold increase versus plasma.[1]

Berberine has the ability to stimulate insulin secretion in pancreatic islet cells as well as HIT-T15 cells, which may also play a role in its anti-diabetic activity. When HepG2 cells produce interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), this results in a state of inflammation which in turn impairs the insulin pathways. Berberine treatment inhibits the production of both IL-6 and TNF-alpha, associated with an improvement in the insulin-signaling cascade. Therefore, berberine may have its effect on enhancing insulin secretion through its anti-inflammatory activity.[1] Berberine may also promote activation of messenger RNA transcription of the insulin receptor, contributing to berberine’s ability to regulate insulin sensitivity.[1]

BERBERINE AND CHOLESTEROL

BERBERINE AS AN ANTIMICROBIAL

Human clinical investigations have shown that berberine supplementation may reduce aspartate and alanine transaminase levels in patients with type 2 diabetes, indicating that berberine may improve liver function.[1] Berberine has also been shown to reduce liver necrosis in both steatosis due to hepatitis C infection as well as nonalcoholic steatosis.[1] Another study demonstrated berberine’s positive effect on its ability to lower hypercholesterolemia specifically LDL-C in elderly hypercholesterolemic patients who were statin-intolerant.[1]

Berberine has also been researched as a treatment for multidrugresistant E. coli.[5] Five multidrug-resistant (MDR) STEC/EPEC and five MDR ETEC isolates from yaks with hemorrhagic diarrhoea were selected for the study.[5] Antibacterial activity of berberine was evaluated, and researchers concluded that berberine may be a good antibacterial treatment against MDR E. coli.[5]

BERBERINE METABOLISM

Berberine has been reported to inhibit both triglyceride and cholesterol synthesis in human hepatoma cells, as well as from primary hepatocytes.[1] Multiple animal studies have demonstrated that berberine can alleviate hyperlipidemia and fatty liver in obese and obese and diabetic rats.[2] In another study, mice consumed a high-fat diet to induce fatty liver, and after sixteen weeks of berberine supplementation there was a 14% reduction in liver lipid content as well as an alleviation of hepatic stenosis.[1]

BERBERINE AND INSULIN

Berberine has been shown to regulate glucose metabolism both in vitro and in vivo.[3] In a pilot study comparing the efficacy of berberine versus metformin in newly diagnosed type 2 diabetic patients, researchers demonstrated that after 3 months, the hypoglycemic effect of berberine (500 mg three times per day) was similar to metformin.[3] Clinical effects in the berberine group included statistically significant decreases in fasting blood glucose, postprandial blood glucose, hemoglobin A1C (HBA1C) and plasma triglycerides.[3] In a follow-up study of adults with poorly controlled type 2 diabetes, patients were administered berberine for 3 months.[3] Berberine was able to lower fasting blood glucose and postprandial blood glucose from week 1 through to the end of the trial. In addition, statistically significant decreases in HBA1C and fasting plasma insulin as well as in total cholesterol and low-density lipoprotein cholesterol were observed.[3] During the trial, 34.5% of patients experienced transient gastrointestinal adverse effects; however, functional liver or kidney damages were not observed in any patients.[3] When berberine dosages were reduced to 300 mg three times per day, gastrointestinal symptoms improved significantly.[3] Researchers concluded that berberine is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism.[3] Berberine may impact insulin levels by upregulating insulin receptor expression. In patients treated with berberine, researchers found a significant elevation in the percentage of peripheral blood lymphocytes that express insulin receptors.[4] Berberine was also effective at lowering fasting blood glucose in patients with chronic hepatitis B or C

For more information visit: www.nfh.ca

IHP 2013-12,2014-01 (Berberine SAP).indd 2

Berberine has been shown to have significant antimicrobial activity against bacteria, fungi, parasites, helminthes, and viruses.[1] Berberine has considerable data against several bacteria including Streptococcus, Salmonella, Klebsiella, Clostridium, Pseudomonas, Proteus, Shigella, Vibrio, and Cryptococcus species, as well as being effective in treating Escherichia coli diarrhea.[1] Data also shows that berberine exerts this positive effect without harming indigenous lactobacilli and bifidobacteria in the intestinal system.[1]

BERBERINE AND GUT FLORA

A study exploring the role of berberine’s effect on endotoxemia in mice found that pretreating cells with berberine protected the endothelial tight junctions against disruption which could potentially have a similar effect on human Caco-2 cells.[1] Therefore, berberine treatment may block endotoxemia from entering into circulation, and thus reduce hepatic inflammation and progression of NAFLD. Researchers have also hypothesized that part of berberine’s beneficial effect in patients with diabetes mellitus is due to its ability to modulate gut flora.[6] Recent evidence suggests that gut flora composition may be associated with obesity and type 2 diabetes, both aliments associated with low-grade inflammation.[6] Since berberine is poorly absorbed, it acts topically in the gastrointestinal system and is able to inhibit bacterial cell division which may play a role in regulating gut flora.[6]

REFERENCES

1. Liu, Y., et al. “Update on berberine in nonalcoholic Fatty liver disease”. Evidence-Based Complementary and Alternative Medicine Vol. 2013 (2013): 308134. 2. Kim, W.S., et al. “Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity”. American Journal of Physiology Vol. 296, No. 4 (2009): E812–E819. 3. Yin, J., H. Xing, and J. Ye. “Efficacy of berberine in patients with type 2 diabetes mellitus”. Metabolism Vol. 57, No. 5 (2008): 712–717. 4. Zhang, H., et al. “Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression”. Metabolism Vol. 59, No. 2 (2010): 285–292. 5. Bandyopadhyay, S., et al. “Potential antibacterial activity of berberine against multi drug resistant enterovirulent Escherichia coli isolated from yaks (Poephagus grunniens) with haemorrhagic diarrhoea”. Asian Pacific Journal of Tropical Medicine Vol. 6, No. 4 (2013): 315–319. 6. Han, J., H. Lin, and W. Huang. “Modulating gut microbiota as an anti-diabetic mechanism of berberine”. Medical Science Monitor Vol. 17, No. 7 (2011): RA164–RA167.

2013-11-11 10:03:48

peer review

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

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

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

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

Aoife Earls, MSc, ND Trafalgar Ridge Chiropractic and Acupuncture 2387 Trafalgar Road, Unit 7A Oakville, Ontario L6H 6K7 aearlsnd@gmail.com Berchman Wong, ND 718 - 33 Canniff St Toronto, Ontario M6K 3M5 berchman.nd@gmail.com Betty Rozendaal, BES, MA, ND Thornhill Naturopathic Health Clinic 12A Centre Street Thornhill, Ontario L4J 1E9 drbetty@thornhillnaturopathic.ca Brock McGregor, ND McGregor Naturopathic 220 St Clair Street Chatham, Ontario N7L 3J7 drbrock@mcgregornd.com

Heidi Fritz, MA, ND Canadian College of Naturopathic Medicine 1255 Sheppard Ave East Toronto, Ontario M2K 1E2 hfritz@ccnm.edu Isaac Eliaz, MD, MS, LAc Amitabha Medical Clinic & Healing Center 7064 Corline Ct #A Sebastopol, California 95472-4528 ieliaz@sonic.net

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

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

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

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

Elaine Lewis, HBSc, ND Back to Play Chiropractic 592 Rathburn Road West Mississauga, Ontario L5B 3A4 elewis@ccnm.edu Elizabeth Cherevaty, BSc, ND Norfolk Chiropractic Wellness Centre 86 Norfolk Street, Suite 101 Guelph, Ontario N1H 4J2 elizabeth.cherevaty@gmail.com

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

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

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

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

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

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

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 Karam Bains, BSc, ND Inside Out Wellness 3650 Langstaff Road, Unit 12 Woodbridge, Ontario karam@elixirhealth.ca Kate Whimster, ND Kew Beach Naturopathic Clinic 2010 Queen Street East, 2nd floor Toronto, Ontario kwhimster@wavelengthwellness.com Kelly Brown, BSc, ND Clinic One 286 McDermont Avenue Winnipeg, Manitoba R3B 1H6 drkbrownnd@gmail.com

November / December 2013 l www.ihpmagazine.com 49

peer review

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

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

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

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

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

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

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

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

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

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

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

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

Meghan MacKinnon, ND Armata Health Centre 126 Welling St. W, Unit 201B Aurora, Ontario L4G 2N9 drmeg.nd@gmail.com Melanie DesChatelets, BSc, ND True Health Studio 200-4255 Arbutus St Vancouver, British Columbia V6J 4R1 melanie@drdeschat.com Misa Kawasaki, BSc, ND Meridian Wellness 13085 Yonge Street, Suite 205 Richmond Hill, Ontario L4E 3S8 drkawasaki@meridianwellness.ca

Shawna Clark, ND Forces of Nature Naturopathic Clinic 2447 1/2 Yonge St Toronto, Ontario M4P 2E7 info@shawnaclarknd.com Stephanie Swinkles, DDS Elmsdale Dental Clinic 4-269 Highway 214 Elmsdale, Nova Scotia N2S 1K1 steph_moroze@hotmail.com Susan Coulter, BSc, ND Roots of Health 2-497 Laurier Ave Milton, Ontario L9T 3K8 scoulter@rootsofhealth.ca

50 www.ihpmagazine.com l November / December 2013

Sylvi Martin, BScN, ND Fusion Chiropractic and Integrative Health 735 Danforth Avenue Toronto, Ontario M4J 1L2 sylvi.martin@gmail.com Tanya Lee, BSc, ND The Health Centre of Milton 400 Main St East Suite 210 Milton, Ontario L9T 1P7 tanyalee.nd@gmail.com Terry Vanderheyden, ND Bayside Naturopathic Medicine 118 Bay Street Barryâ&#x20AC;&#x2122;s Bay, Ontario KOJ 1B0 doctrv@gmail.com Theresa Jahn, BSc, ND Living Well Integrative Health Centre 2176 Windsor Street Halifax, Nova Scotia B3K 5B6 info@theresajahn.com

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.

editorial board

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

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

Jason Boxtart, ND

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

Ben Boucher, MD

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

November / December 2013 l www.ihpmagazine.com 53

editorial board

Pardeep Nijhawan, MD, FRCP(C), FACG

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

Gurdev Parmar, ND, FABNO

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

Kristy Prouse, MD, FRCSC

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

Dugald Seely, ND, MSc

Dr Seely is a naturopathic doctor and director of research at the Canadian College of Naturopathic Medicine (CCNM). Dugald completed his masters of science in cancer research from the University of Toronto with a focus on interactions between chemotherapy and natural health products. In his current role as director of research, Dugald is the principal investigator for a number of clinical trials, and is actively pursuing relevant synthesis research in the production of systematic reviews and meta-analyses. Ongoing projects include three 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.

54 www.ihpmagazine.com l November / December 2013

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The Journal of IHP

Chemotherapy-Related Cognitive Impairment Strategies for intervention By Meighan Valero, ND Meighan Valero, ND Be Well 3449 Walker Road, Suite One,â&#x20AC;¨ Windsor, Ontario,â&#x20AC;¨N8W 3S2

Abstract Chemotherapy-related cognitive impairment (CRCI) is characterized by memory loss, lack of concentration and attention, difficulty multitasking, organizing, planning, and thinking. CRCI can have a significant impact on quality of life but treatment options with strong supporting evidence of efficacy are scarce. This review highlights the current state of evidence regarding CRCI and therapies that may help improve cognitive function in this patient population.

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Introduction

Chemobrain, also referred to as chemofog, or chemotherapy-related cognitive impairment, is a phenomenon that has been reported by patients receiving various forms of chemotherapy for the past three decades. Estimates of chemotherapyrelated cognitive decline (CRCI) in breast cancer survivors are as high as 75% (Ahles 2002, Brezden 2000, Schagen 1999, Tchen 2003, Van Dam 1998). The cognitive impairment is typically characterized by memory loss, lack of concentration and attention, difficulty thinking, organizing, planning, and multi-tasking (Matsuda 2005, Reid-Arndt 2009). While it was generally accepted by the 1990s that chemotherapeutic agents could be acutely neurotoxic when delivered directly to the nervous system, CRCI was still regarded as psychogenic (Hede 2008, Myers 2009). Given the inability of many chemotherapeutic agents to cross the blood-brain-barrier, it was believed that chemotherapy was an unlikely cause of neurotoxicity when administered systemically (Oâ&#x20AC;&#x2122;Farrell 2013). Many confounding factors such as psychological distress associated with having cancer, fatigue, anxiety, depression, and effects of medication prescribed in conjunction with chemotherapeutic intervention, all can alter cognitive function as well. Due to advancements in cancer treatment, there is also increased survival. As a result, there are a rising number of patients who are living with long-term side effects of these anti-cancer agents, which can have significant negative impacts on quality of life.

Impact on Quality of Life

In a 2010 survey conducted by the Canadian Breast Cancer Network, women who had received chemotherapy had the greatest reduction in house-hold income, took more time off work, were more likely to have had to quit their jobs, and had a greater perception that the financial burden imposed by their illness would impact their long-term health (Dunbrack 2010). In a study by Reid-Arndt et al., women with stages I-III breast cancer were

evaluated one month after completing adjuvant chemotherapy. Data was collected regarding cognitive, emotional, social, and vocational functioning and an association between executive functioning deficits and decreased productivity, community involvement, and social role functioning was found (2009).

Advancements in Research

Studies on CRCI in the recent past reported poor, if any, correlation between subjective reports of cognitive decline and objective measures of cognitive performance (Biglia 2012, Hutchinson 2012, Jansen 2011). In order to establish appropriate guidelines for study design and methodology when performing research in this field, the International Cognition and Cancer Task Force (ICCTF) was created in 2006. This aided tremendously in promoting comparable findings among studies and reducing the number of confounding variables in the research (Wefel 2008). Dr. Patricia Ganz conducted one of the first studies demonstrating that cognitive complaints after breast cancer treatment are associated with neuropsychological test performance. Her team enrolled 189 breast cancer patients one month post surgery, with or without radiation and/or chemotherapy, and prior to commencing hormone therapyâ&#x20AC;&#x201D;a common confounding factor. The control group consisted of a sample of age-matched healthy women and found that 23.3% of the breast cancer patients reported higher memory complaints and 19% had higher executive function complaints post-treatment; >1 SD above the mean for healthy control sample (Ganz 2013). McDonald et al. performed the first controlled prospective MRI study in the field of neuroimaging whereby significant decreases in gray matter density were found in bilateral, frontal, temporal, and cerebellar regions as well as the right thalamus in breast cancer patients shortly following chemotherapy treatment. These changes were not evident in either a disease or healthy control group.

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The cognitive changes could also not be accounted for by postsurgical effects, disease stage, psychiatric symptoms, psychotropic medication, or hormonal treatment status, suggesting the changes were due to chemotherapy treatment (2010). No other study had prospectively examined gray matter changes in patients both receiving and not receiving chemotherapy with a pre-treatment baseline with which to compare post-treatment changes. This groundbreaking study was the first to show decline in brain gray matter density shortly after chemotherapy and degree of long-term recovery via a prospective longitudinal approach.

Evidence-Based Interventions

Modafinil Sixty-eight participants with memory problems persisting two years post-chemotherapy treatment for breast cancer were given 200mg daily of Modafinil (a psychostimulant used in the treatment of patients with narcolepsy) for four weeks, finding modest but statistically significant improvement in speed of memory and episodic memory, but not in working memory, compared with controls (Kohli 2009, Von 2011). Other groups have tried a one-time dose of 200mg, finding improvement in attention and psychomotor speed but not in working memory (Lundorff 2009). In another study by Blackhall et al., initial doses of 100mg Modafinil for two weeks, increasing to 200mg daily in 27 patients with cancer of all stages, did not show improvement in cognitive functioning. Due to the mixed results and small sample sizes, effectiveness of this medication for the treatment of CRCI has not been established (2009).

Exercise

Korstjens evaluated the effects of a 12-week rehabilitation program combining exercise with a psychoeducational program on various aspects of quality of life, including cognition. Physical exercise sessions overseen by a physiotherapist occurred twice a week for two hours and included aqua aerobics, group sports, or individual endurance and strength training. The psychoeducational program consisted of seven two-hour sessions focused on coping with cancer. Improvements in global cognitive function were reported based on two items on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (2006). Although some improvements were reported in cognitive function in this and other studies (Schwartz 2002), it is difficult to determine the effect of an exercise intervention on cognitive impairment because of the difference in definition and delivery of the exercise intervention programs, small sample sizes, and study designs (combined multiple interventions). Further research is required.

Natural Environment Intervention

Attention-restoring theory identifies that the environment may influence oneâ&#x20AC;&#x2122;s ability to concentrate and capacity to direct attention (Cimprich 2003); thus, natural restorative environmental interventions may replenish psychological reserves and improve cognitive functioning. Two studies were found that evaluated the impact of natural restorative environmental intervention on cognitive function in patients with cancer (Cimprich 1993, Cimprich 2003). Cimprich examined the impact of a natural restorative environmental intervention (walking in nature or gardening for 20-30 minutes three times a week) in 32 patients with breast cancer and assessed their level of attention at three, 18, 60, and 90 days after surgery. Significant and sustained improvement in attentional fatigue scores were noted across all four time periods (1993). Similarly, in a follow-up randomized, controlled trial of 157 patients with breast cancer, Cimprich and Ronis demonstrated that those who were exposed to the natural environment for 120 minutes per week had improved capacity to direct attention from pretreatment as compared with the nonintervention group, even after controlling for age, education, attention scores prior to surgery, other health problems, distress, and extent of the surgery (2003). Additional longitudinal research is needed to understand its sustainability throughout the 58 www.ihpmagazine.com l November / December 2013

The Journal of IHP

course of cancer treatment, as well as to test outcomes in other cancer populations.

Acetyl-L-Carnitine

Though not yet clinically tested for cognitive impairments due to chemotherapy, ALC improved memory, visuo-spatial capacity, and vocabulary recall when given at two grams per day over a test period of three months in cognitively impaired ex-alcoholics aged 30-60 years (Tempesta 1990). In controlled trials, ALC improved depression as well as cooperation, sociability, and attention to personal appearance, though it did not consistently improve anxiety (Bonavita 1986). Dosage ranges from 1,500-3000mg per day with most trials using two grams or more (Kidd 1999).

Given that acetyl-L-carnitine aids in the treatment/prevention of chemotherapy-induced peripheral neuropathy (CIPN) and that CIPN can be caused by chemotherapeutic agents such as Paclitaxel and Cisplatinâ&#x20AC;&#x201D; known to also cause chemotherapy-related cognitive impairmentâ&#x20AC;&#x201D;the use of ALC may help to target more than one of these side effects which may impact quality of life significantly (Pisano 2003).

Phosphatidylserine (PS)

PS is present in all cells of the human body and particularly in the membrane systems of nerve cells. While also not clinical studied for CRCI, phosphatidylserine consistently benefits memory, learning, concentration, word choice, mood, and relieves anxiety and depression, and the November / December 2013 l www.ihpmagazine.com 59

capacity to cope with stress (Crook 1992, Kidd 1998, Maggioni 1990). Effective intakes of PS range from 100mg per day (for smaller children and for maintenance in healthy adults) to 300mg/day for memory loss and up to 600mg/day for mood enhancement (Kidd 1998).

Conclusion

For the past several decades research on CRCI has focused on proving whether this side effect is psychogenic or neurological in nature. With studies now using advanced neuroimaging techniques, new research may attempt to elucidate mechanisms by which various chemotherapeutic agents may be causing cognitive decline in patients with other forms of cancer, not limited to breast cancer. Insight into mechanisms of action will in turn allow for more research regarding treatment and prevention of CRCI. Sample sizes of the majority of the present studies are too small to make appropriate inferences about any conclusions made. Patient populations in these studies are typically females with breast cancer and not representative of all other types of cancer.

References Ahles TA, Saykin AJ, Furstenberg CT, et al. Neuropsychologic impact of standard dose chemotherapy in long-term survivors of breast cancer and lymphoma. J Clin Oncol. 2002;20:485-493. Biglia N, Bounous VE, Malabaila A, et al. Objective and self-reported cognitive dysfunction in breast cancer women treated with chemotherapy: a prospective study. Eur J Cancer Care. 2012;21:485-92. Blackhall, L., Petroni, G., Shu, J., Baum, L., & Farace, E. A pilot study evaluating the safety and efficacy of modafinil for cancer-related fatigue. Journal of Palliative Medicine. 2009;12:433-439. Bonavita E. Study of the efficacy of tolerability of L-acetyl carnitine therapy in the senile brain. Intn J Clin Pharmacol Ther Toxicol. 1986;24:511-516. Brezden CB, Phillips KA, Abdolell M, et al. Cognitive function in breast cancer patients receiving adjuvant chemotherapy. J Clin Oncology. 2000;(18):2695-2701. Cimprich B. Development of an intervention to restore attention in cancer patients. Cancer Nursing. 1993;16:83-92. Cimprich, B., & Ronis, D.L. An environmental intervention to restore attention in women with newly diagnosed breast cancer. Cancer Nursing. 2003;26:284-292. Crook T, Petrie W, Wells C, Massari DC. Effects of phosphatidylserine in Alzheimerâ&#x20AC;&#x2122;s disease. Psychopharmacol Bull. 1992;28:61-66. 60 www.ihpmagazine.com l November / December 2013

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Dunbrack J. Breast cancer: Economic impact and labour force re-entry. Ottawa: Canadian Breast Cancer Network, 2010. Web. 27 Jul 2013 <http://www.cbcn.ca/documents/ Labour_Force_Re-Entry_Report_ENG_CBCN_2010.pdf> .

McDonald BC, Conroy SK, Ahles TA, West JD, Saykin AJ. Gray matter reduction associated with systemic chemotherapy for breast cancer: a prospective MRI study. Breast Cancer Res Treat. 2010 Oct;123(3):819-828.

Ganz PA, Kwan L, Castellon SA, Oppenheim A, Bower JE, Silverman DH, Cole SW, Irwin MR, Ancoli-Israel S, Belin TR. Cognitive complaints after breast cancer treatments: examining the relationship with neuropsychological test performance. J Natl Cancer Inst. 2013 Jun 5;105(11):791-801.

Myers JS. Chemotherapy-related cognitive impairment. Clin J Oncol Nurs. 2009;13(4):413-421.

Jansen CE, Cooper BA, Dodd MJ et al. A prospective longitudinal study of chemotherapyinduced cognitive changes in breast cancer patients. Support Care Cancer. 2011;19:1647-1656. Kidd PM. A review of nutrients and botanicals in the integrative management of cognitive dysfunction. Altern Med Rev. 1999 Jun;4(3):144-161.

Pisano C, Pratesi G, Laccabue D, et al. Paclitaxel and Cisplatin-induced neurotoxicity: a protective role of acetylL-carnitine. Clin Cancer Res 2003;9(15)5756-67. Reid-Arndt, SA. Breast cancer and “chemobrain”: the consequences of cognitive difficulties following chemotherapy and the potential for recovery. Mo Med. 2009;106(2):127-131. Schagen SB, van Dam FS, Muller MJ, et al. Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. Cancer. 1999;85:640-650.

Kidd PM. Phosphatidylserine. Number one Brain Booster. New Canaan, CT.: Keats Publishing; 1998.

Schwartz AL, Thompson JA, Masood N. Interferoninduced fatigue in patients with melanoma: A pilot study of exercise and methylphenidate [Online exclusive]. Oncology Nursing Forum. 2002;29:E85-E90.

Kohli S, Fisher SG, Tra Y, Adams MJ, Mapstone ME, Wesnes KA, Roscoe JA, Morrow GR. The effect of modafinil on cognitive function in breast cancer survivors. Cancer. 2009 Jun 15;115(12):2605-16.

Tchen N, Juffs JG, Downie FP, et al. Cognitive function, fatigue, and menopausal symptoms in women receiving adjuvant chemotherapy for breast cancer. J Clin Oncology. 2003;21:4175-4183.

Korstjens I, Mesters I, van der Peet E, Gijsen B, van den Borne B. Quality of life of cancer survivors after physical and psychosocial rehabilitation. European Journal of Cancer Prevention. 2006;15:541-547.

Tempesta E, Troncon R, Janiri L, et al. Role of acetyl-Lcarnitine in the treatment of cognitive deficit in chronic alcoholism. Int J Clin Pharmacol Res. 1990;10:101-107.

Lundorff LE, Jonsson BH, Sjogren P. Modafinil for attentional and psychomotor dysfunction in advanced cancer: A double-blind randomised, cross-over trial. Palliative Medicine. 2009;23:731-738. Maggioni M, Picotti GB, Bondiolotti GP, Panerai A, Cenacchi T, Nobile P, Brambilla F. Effects of phosphatidylserine therapy in geriatric patients with depressive disorders. Acta Psychiatr Scand. 1990 Mar; 81(3):265-270. Matsuda T, Takayama, T, Tashiro M. et al. Mild cognitive impairment after adjuvant chemotherapy in breast cancer patients –evaluation of appropriate research design and methodology to measure symptoms. Breast Cancer. 2005;12:279-287.

Van Dam FSAM, Schagen SB, Muller MJ, et al. Impairment of cognitive function in women receiving adjuvant treatment for high-risk breast cancer: high-dose versus standard-dose chemotherapy. J Natl Cancer Inst. 1998;90:210-218. Von Ah D, Jansen C, Allen DH, Schiavone RM, Wulff J. Putting evidence into practice: evidence-based interventions for cancer and cancer treatment-related cognitive impairment. Clinical Journal of Oncology Nursing. 2011 Dec; 15(6):607-15. Wefel JS, Vardy J, Ahles T, et al. Cancer and cancer-related cognitive dysfunction: an international perspective from the Venice cognitive workshop. Ann Oncol. 2008;19:623-9.

Hede, K. Chemobrain is real but may need new name. J Natl Cancer Inst. 2008;100(3):162-169. Hutchinson AD, Hosking JR, Kichenadasse G, et al. Objective and subjective cognitive impairment following chemotherapy for cancer: a systematic review. Cancer Treat Rev. 2012;38:926-34.

O’Farrell, E, Mackenzie J, Collins B. Clearing the Air: A Review of Our Current Understanding of “Chemo Fog.” Current Oncology Reports. 2013 Jun;15(3):260-9.

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Diabetes Medications Reduced risk of disease-related complications? By William R. Ware, PhD William R Ware, PhD Emeritus Professor, Faculty of Science University of Western, Ontario warewr@rogers.com

Abstract It is not debatable that the elevated blood glucose levels associated with diabetes represent a serious risk marker for macrovascular and microvascular adverse developments and events, and that the risk increases with the average of the daily fluctuations. This provides the principal rationale for maintaining both fasting blood glucose and the indicator of the long- term average, glycated hemoglobin, at levels close to normal. More than a dozen prescription drugs are currently used individually or in combination to treat type 2 diabetes. They act by decreasing liver glucose production, increasing insulin secretion, increasing insulin sensitivity, inhibiting glucagon release and slowing the absorption of carbohydrates. These drugs decrease serum glucose and glycated hemoglobin with the goal of glucose reduction to targets approaching normal, a result that is generally believed will significantly decrease the incidence of the complication associated with the disease. Failure to achieve blood glucose control generally results in additional drugs and even insulin, and is frequently termed intensive treatment. As will be discussed, there are not only new studies but recent meta-analyses that have examined the impact of intensive blood glucose lowering on complications in type 2 diabetes. Evidence will be presented that in fact glucose lowering, either intensive or not, is a failed therapy if judged by the impact on clinical complications, a failure termed by some medical scientists the Diabetes Paradox.

62 www.ihpmagazine.com l November / December 2013

The Journal of IHP Introduction

Even before the beginning of the 20 century, carbohydrate restriction was the established medical response to diabetes and obesity. This changed dramatically in the early 1960s when the hypothesis that fat and in particular saturated fat increased the risk of both heart disease and cancer was accepted as true without adequate evidence and profoundly altered diets. The macronutrients that were most effective in driving up blood sugar, elevating insulin, and viewed as causing insulin resistance, beta cell dysfunction and diabetes became the main components of the so-called healthy, low fat diet in the developed world. These were mostly carbohydrates and as the trend accelerated, these were more refined and had higher glycemic activity. Then drugs became available which would lower blood sugar and its daily average and offered a logical solution. The number of antihyperglycaemic agents increased rapidly. If used intensively, the drugs were able to bring glucose levels down to somewhat above normal and this was viewed as a success. Thus the blood glucose elevations associated with diets rich in carbohydrates were counteracted, once diabetes had developed, by daily dosing with antihyperglycemic drugs. The impact on complications, the principal reason for glucose control, is however a developing story and the subject of this article. In what follows, the evidence will be presented that once one has diabetes, controlling both the daily fluctuations and lowering the long-term average of blood glucose with pharmaceutical intervention in fact has almost no impact on the incidence of complications. This is not good news for patients with diabetes who obviously have reason to be seriously concerned about the need to prevent complications. th

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Standard vs. Intensive glucose control

There has been great interest in intensive blood glucose control and the natural (or perhaps simplistic) assumption has been that lowering levels to the pre-diabetic range with multiple drugs, insulin and dose escalation would be beneficial. The wake-up call came in 2008. Two papers simultaneously published in the New England Journal of Medicine reported on studies designed to address this issue with large

cohorts. The ACCORD study randomized 10,251 patients with type 2 diabetes to receive intensive therapy targeted with polypharmacy, increased doses and insulin if necessary, all directed at getting HbA1c down from a median level of 8.1% to below 6.0%, generally considered high-normal or pre-diabetic. The controls received standard drug therapy targeting a level of 7.0% to 7.9%. As compared with standard therapy, the use of intensive therapy for 3.5 years increased mortality resulting in early trial termination and did not significantly reduce major cardiovascular events (Gerstein 2008). The ADVANCE study randomized 11,140 patients with type 2 diabetes to either standard glucose control using mostly oral glycemic drugs or an intensive intervention group mainly using the modified release sulfonylurea Gliclazide, plus other drugs including insulin if needed to achieve a HbA1c of 6.5%. For over a median five- year follow-up, there was a small (1.9%) absolute decrease in risk associated with the primary endpoint, combined micro- and macrovascular events, in the intensive treatment group. But this was due to new or worsening nephropathy. Among 14 secondary endpoints, only new-onset miroablinuria showed a decreased absolute risk of 2%. Thus there was no impact on the remaining common complications of type 2 diabetes including all cause mortality, major or all coronary events, all cerebrovascular events, peripheral vascular events, visual deteriation or new or worsening neuropathy (Patel 2008). A smaller trial, the Veterans Affairs Diabetes Trial (VADT) that reported in 2009, involved a comparison between intensive and standard glucose control in patients with type II diabetes with suboptimal response to therapy. In this study 1791 men, mean age 60, were randomized to two groups with a median follow-up of 5.6 years. Median HbA1c dropped from 8.4% in the standard therapy group to 6.9% in the intensive group. The primary endpoint was the time from randomization to first occurrence of a major cardiovascular event, which was a composite of MI, stroke, deaths from cardiovascular causes, congestive heart failure, surgery for vascular disease, inoperable coronary disease November / December 2013 l www.ihpmagazine.com 63

The Journal of IHP and amputation for gangrene. The comparison was with standard drug therapy. It was found that intensive glucose control had no significant impact on the endpoints of major cardiovascular events, death or microvascular complications with the exception of evidence of the progression to kidney disease. Statistically significant increased incidence of nephropathy was seen in subgroup analysis when micro- and macroalbuminuria were combined (Duckworth 2009). In 2011 a systematic review and meta-analysis of randomized trials concerning intensive glycemic control appeared in BMJ (Hemmingsen 2011). No impact on all cause mortality was found. With regard to other endpoints, the authors found that data available remained insufficient to prove or refute a relative risk reduction of CVD mortality, non-fatal MI, composite microvascular complications, or retinopathy at a relative risk reduction threshold they considered clinically significant, but identified a 30% increase in severe hypoglycemia. Prompted by the ADVANCE and VADT results and earlier studies related to kidney complications, a study involving meta-analysis reporting in 2012 investigated if intensive vs. standard glucose control decreased significant renal clinical outcomes such as doubling of serum creatinine levels, end-stage renal disease or death from renal disease during the years of follow-up. No evidence was found when seven trials with follow-up from two to 15 years were evaluated (Coca 2012).

Metformin monotherapy

The standard care almost always involves either metformin alone or metformin plus another drug. Since the American Diabetes Association (ADA) recommends metformin as the first-line of standard care after diagnosis of type 2 diabetes (ADA 2012), to what extent does it reduce the macro- and microvascular complications of diabetes when compared with a placebo or non-drug treatment such as diet? This may seem like an odd issue bring up. Metformin has been used for decades. Metformin is also the most common standard against which other drugs are judged in clinical trials. In 2012 a meta-analysis was published where the efficacy of metformin was examined. The trials were either metformin vs. diet or non-drug care or a placebo, metformin plus a sulphonylurea vs. the sulphonylurea alone, or metformin plus insulin vs. insulin plus a placebo or metformin vs. total withdrawal from the drug. For the above comparisons, no significant benefit was found for all-cause mortality, cardiovascular mortality, all MI, all strokes, congestive heart failure, peripheral vascular events, amputation, or microvascular events (Boussageon 2012). It is also important to look at just the studies in the above meta-analysis where metformin alone was compared with a placebo, diet or usual non-drug care and there were more 64 www.ihpmagazine.com l November / December 2013

than a few events. There are only two studies with longer than 12 months follow-up (Rachmani, 2002, UKPDS-34 1998), and only the endpoints of all cause mortality, cardiovascular mortality and all MI (heart attacks) were common to these studies. A third study lasting only 12 months was not judged relevant but was in fact negative (Cryer 2005). If the results from the two eligible studies are pooled and given equal weight (in the above meta-analysis they were given approximately equal weight), then as shown in the table below, for the three endpoints there was no statistically significant benefit found (95% confidence interval contains 1.0) These two studies together involved 537 subjects in the treated group and 609 in the control group. Pooled analysis of two trials of metformin vs. diet (UKPDS-34 1998) or metformin withdrawal (Rachmani 2002) ENDPOINT All MI All cause mortality Cardiovascular mortality

ODDS RATIO 0.77 0.80 0.79

95% CI 0.57 - 1.04 0.671 - 1.06 0.58 - 1.10

The withdrawal study obtained only non-significant results indicating no benefit. The UKPDS-34 study is generally the only trial cited to justify the use of metformin because it claimed to have obtained evidence of benefit (UKPDS-34 1998). This study actually started in 1983 and reported finally in 1998. Over this period, the primary and main endpoints were changed a number of times and the announced termination date repeatedly extended. Furthermore, the study was not blinded for the investigators and the results of interim analysis were available. This study protocol is obviously open to bias. To quote one citric, “It seems that the authors continued the study until they obtained a result that was significant without adjusting for repeatedly looking at the data” (Ewart 2001). An investigator involved in the trial commented in 2008 that “UKPDS-34 broke almost all the rules of trial design. We are taught to believe that a study protocol should be predetermined and set in stone, but this study went to the other extreme, elevating the ad hoc into an art form” (Gale 2008). Thus the key study appears flawed. In 2009 it was pointed out (Reaven 2009), based on the six-year report from UKPDS (UKPDS-16 1995), that following enrolment there was a progressive deteriation of glycemic control in all groups including those assigned to intensive control. In addition, beta cell function was estimated by HOMA-β and the investigators concluded that increasing hyperglycemia and decreasing beta cell function were significant features irrespective of the drug protocol used. Reaven also points out that the loss of secretory function does not appear to be inexorable and cites two studies where weight loss improved glycemic control. This view is supported by a study discussed below (Lim 2011).

The Journal of IHP The 2012 American Diabetes Association (ADA) Standards of Medical Care in Diabetes clearly indicates that metformin should be initiated as therapy for type 2 diabetes at the time of diagnosis. If the patient has markedly elevated blood glucose or HbA1c, then the advice is to consider insulin with or without oral agents. If metformin alone does not achieve or maintain satisfactory HbA1c levels over three to six months at maximal tolerated doses, the recommendation is to add a second oral agent (ADA 2012). This more intensive treatment is of course the subject of the several major studies discussed above which in general found no benefit. Furthermore, in the intensive vs. standard glucose lowering studies, metformin, the common reference treatment, itself does not appear to be effective. It is in fact quite remarkable that UKPDS-34 is the study used to justify metformin as the primary treatment and the drug used as a principal standard against which other drugs are tested.

Discussion and conclusions

There appears to be only very weak if any evidence regarding the ability of current drug treatments to significantly reduce the incidence of the many complications of type 2 diabetes, independent of the HbA1c level achieved. Among some diabetes researchers this is acknowledged and is termed the Diabetes Paradox, i.e. hyperglycemia is necessary for the development of late diabetic complications but average blood glucose (HbA1c) explains only a small percentage of complications (Bierhause 2011). Concerned researchers are now looking into the complex details of type 2 diabetes such as for example the potential for reactive glucose metabolites and their intermediates to act as active agents in the disease etiology and progression (Fleming 2012). There is obviously an urgent need for a new treatment paradigm rather than to merely reduce markers such as HbA1c. In the past few years there have been calls (from the wilderness) for a return to the traditional approach used for decades for treating type 2 diabetes, the adoption of carbohydrate restriction in the context of both prevention and therapy (Accurso 2008, Leite 2009, Volek 2005a, Volek 2005b, Volek 2008, Volek 2009). However, such proposals face strong opposition from those who fear the substitution of fat for carbohydrates, even though there is compelling literature indicating that such fears are groundless (Ware 2012). The success achieved by Richard K. Bernstein using carbohydrate restriction and carefully selected carbohydrates matched to the individualâ&#x20AC;&#x2122;s metabolism is now documented in several editions of his book Dr. Bernsteinâ&#x20AC;&#x2122;s Diabetes Solution (Bernstein 2011). The HbA1c levels he achieves are significantly better than anything conventional medicine appears able to accomplish, and this is generally only with diet. In fact, a recent study found complete reversal of type 2 diabetes achieved over a short period by a starvation diet, and

the benefits appear durable after return to higher calorie intake, strongly suggesting beta-cell regeneration and a permanent increase in insulin sensitivity (Lim 2011). Are type 2 diabetes patients being given a false sense of security? They are told they need to get their blood glucose under control and many attempt to accomplish this in the belief that this reduces the risk of complications, which does not seem to be the case. The net result is a missed opportunity to restrict carbohydrates and calories and thus address the role of insulin in both insulin resistance, fat storage, and leptin resistance, deal with obesity and the metabolic syndrome, and also build muscle with resistance exercise to help increase insulin sensitivity. Another missed opportunity involves alternative medicines such as curcumin, which has produced better glucose control than prescription drugs and even appears to have reversed type 2 diabetes (Chuengsamarn 2012, Na 2012). Those who argue, probably with some justification, that severe carbohydrate restriction is not practical and adherence nearly impossible are also admitting that progress in reducing the complications of diabetes is at present nearly hopeless.

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Patel,A., MacMahon,S., Chalmers,J., Neal,B., Billot,L., Woodward,M., Marre,M., Cooper,M., Glasziou,P., Grobbee,D., Hamet,P., Harrap,S., Heller,S., Liu,L., Mancia,G., Mogensen,C.E., Pan,C., Poulter,N., Rodgers,A., Williams,B., Bompoint,S., de Galan,B.E., Joshi,R. and Travert,F. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358(24): 2560-2572. Rachmani,R., Slavachevski,I., Levi,Z., Zadok,B., Kedar,Y. and Ravid,M. Metformin in patients with type 2 diabetes mellitus: reconsideration of traditional contraindications. Eur J Intern Med 2002; 13(7): 428.

Cryer,D.R., Nicholas,S.P., Henry,D.H., Mills,D.J. and Stadel,B.V. Comparative outcomes study of metformin intervention versus conventional approach the COSMIC Approach Study. Diabetes Care 2005; 28(3): 539-543. Duckworth,W., Abraira,C., Moritz,T., Reda,D., Emanuele,N., Reaven,P.D., Zieve,F.J., Marks,J., Davis,S.N., Hayward,R., Warren,S.R., Goldman,S., McCarren,M., Vitek,M.E., Henderson,W.G. and Huang,G.D. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009; 360(2): 129-139. Ewart,R.M. The case against aggressive treatment of type 2 diabetes: critique of the UK prospective diabetes study. BMJ 2001; 323(7317): 854-858. Fleming,T., Cuny,J., Nawroth,G., Djuric,Z., Humpert,P.M., Zeier,M., Bierhaus,A. and Nawroth,P.P. Is diabetes an acquired disorder of reactive glucose metabolites and their intermediates? Diabetologia 2012; 55(4): 1151-1155. Gale,E.A. Glucose control in the UKPDS: what did we learn? Diabet. Med 2008; 25 Suppl 2: 9-12. Gerstein,H.C., Miller,M.E., Byington,R.P., Goff,D.C., Jr., Bigger,J.T., Buse,J.B., Cushman,W.C., Genuth,S., IsmailBeigi,F., Grimm,R.H., Jr., Probstfield,J.L., Simons-Morton,D.G. and Friedewald,W.T. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358(24): 2545-2559. Hemmingsen,B., Lund,S.S., Gluud,C., Vaag,A., Almdal,T., Hemmingsen,C. and Wetterslev,J. Intensive glycaemic control for patients with type 2 diabetes: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. BMJ 2011; 343: d6898. Leite,J.O., DeOgburn,R., Ratliff,J.C., Su,R., Volek,J.S., McGrane,M.M., Dardik,A. and Fernandez,M.L. Lowcarbohydrate diet disrupts the association between insulin resistance and weight gain. Metabolism 2009; 58(8): 1116-1122. Lim,E.L., Hollingsworth,K.G., Aribisala,B.S., Chen,M.J., Mathers,J.C. and Taylor,R. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 2011; 54(10): 2506-2514. Na,L.X., Li,Y., Pan,H.Z., Zhou,X.L., Sun,D.J., Meng,M., Li,X.X. and Sun,C.H. Curcuminoids exert glucose-lowering 66 www.ihpmagazine.com l November / December 2013

Reaven,G.M. HOMA-beta in the UKPDS and ADOPT. Is the natural history of type 2 diabetes characterised by a progressive and inexorable loss of insulin secretory function? Maybe? Maybe not? Diab. Vasc Dis Res 2009; 6(2): 133-138. UKPDS-16 U.K. prospective diabetes study 16. Overview of 6 yearsâ&#x20AC;&#x2122; therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group. Diabetes 1995; 44(11): 1249-1258. UKPDS-34. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352(9131): 854-865. Volek,J.S. and Feinman,R.D. Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction. Nutr Metab (Lond) 2005a; 2: 31. Volek,J.S., Fernandez,M.L., Feinman,R.D. and Phinney,S.D. Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome. Prog. Lipid Res 2008; 47(5): 307-318. Volek,J.S. and Forsythe,C.E. The case for not restricting saturated fat on a low carbohydrate diet. Nutr Metab (Lond) 2005b; 2: 21. Volek,J.S., Phinney,S.D., Forsythe,C.E., Quann,E.E., Wood,R.J., Puglisi,M.J., Kraemer,W.J., Bibus,D.M., Fernandez,M.L. and Feinman,R.D. Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids 2009; 44(4): 297-309. Ware,W.R. Saturated fat. Friend, foe or simply neutral. Integrated Healthcare Practitioners 2012; 5(2): 68.

The Journal of IHP

Vitamin B12

Update On Clinical Applications By Christopher Habib, ND and Brock McGregor, ND Christopher Habib, ND Clinic Director Mahaya Forest Hill 102-73 Warren Road Toronto, ON M4V 2R9 info@chrishabibnd.com Brock McGregor, ND McGregor Naturopathic 220 St Clair Street Chatham, Ontario N7L 3J info@mcgregornd.com

Introduction

Abstract Vitamin B12 is an essential co-factor for methionine synthase and L-methyl-malonyl-CoA mutase, which are required in DNA synthesis and vital in hematopoietic pathways. There are several risk factors for B12 deficiency and associated anemia, including vegetarian or vegan diets and increasing age. Supplemental vitamin B12 is overwhelmingly safe and although there is insufficient evidence to establish the best long term route of administration for B12, the evidence suggests that oral, intramuscular, and parenteral administration are equally effective. Homocysteine and vitamin B12 levels should be routinely checked in individuals with cognitive decline and Alzheimerâ&#x20AC;&#x2122;s disease, as vitamin B12 is a viable treatment option. The totality of evidence is unclear as to the independent impact of vitamin B12 in relation to cardiovascular risk, but key studies will be discussed. Vitamin B12 is effective at ameliorating the symptoms of depression, as shown by improvements in various validated questionnaires. This article reviews the trials conducted using supplemental vitamin B12 in the treatment of these various health conditions and provides a clinical update.

Vitamin B12, also known as cobalamin, can come in many forms including cyano-, methyl-, and hydroxy-cobalamin, among others (Oâ&#x20AC;&#x2122;Leary 2010). It is involved in many physiological pathways in the body and a deficiency causes megaloblastic anemia, as well as a potential host of other damaging consequences. Serum B12 is currently the principle means of assessing B12 status (Carmel 2009), and as discussed below this test alone is insufficient for accurately establishing all stages of B12 deficiency. The addition of holotranscobalamin, methylmelonic acid, and homocysteine to the standard serum B12 measurement provides a more accurate assessment of functional B12 status (Herrmann

2003). Utilizing this expanded four test profile to assess B12 status can help to identify earlier stages of deficiency and initiate appropriate treatment before the manifestation of clinically evident deficiency symptoms (Herrmann 2003). Supplemental vitamin B12 is overwhelmingly safe and no toxic effects have been encountered from administration, indicating that B12 is essentially nontoxic (Food and Nutrition Board 1998). This is applicable when administering amounts at or below the recommended dietary allowance. However, there is limited data for high-dose B12 and there have been some reports of mild side effects such as rash, pruritus, and diarrhea. There is also not enough data to make any conclusions about the safety of large doses November / December 2013 l www.ihpmagazine.com 67

of vitamin B12 in pregnancy and breast feeding. In addition to anemia, vitamin B12 has been used as a treatment for numerous health issues, including for cardiovascular health, in depression, and for cognitive health. This article will review the evidence available in each of these areas and update practitioners on the clinical applications of vitamin B12.

Anemia

Recent estimates suggest up to 14% of anemias may be associated with folate or vitamin B12 deficiency (Pang 2012). Vitamin B12 is an essential co-factor for methionine synthase and L-methyl-malonyl-CoA mutase, which are required in DNA synthesis and thus vital in hematopoietic pathways (O’Leary 2010). There are several risk factors for B12 deficiency and associated anemia, including vegetarian and vegan diets (Pawlak 2013), and increasing age (Chatthanawaree 2013, Park 2006). An important and often overlooked risk of vitamin B12 deficiency is depletion from drug interactions including proton pump inhibitors, metformin, anti-seizure medications, and nitric oxide (Mazokopakis 2008). Also of interest is a recent study indentifying an increased risk of vitamin B12 (as well as folate and iron) deficiency in patients following gastric bypass, with over 60% developing anemia within three years (Vargas-Ruiz 2008). The most common anemia associated with vitamin B12 is pernicious anemia (PA), a macrocytic anemia caused by atrophic gastritis and an associated loss of intrinsic factor (IF), which is required to cleave vitamin B12 from protein sources thereby facilitating absorption (Stabler 2013). PA is most common in the seventh or eighth decade of life, with milder atrophic gastritis affecting an estimated 20% of older individuals (Stabler 2013). Long term risk factors of neurologic complications including peripheral neuropathy, and lateral spinal cord and cerebrum lesions, can be prevented or reversed if PA is recognized early in disease progression and supplemental vitamin B12 is provided (Annibale 2011). Since oral supplements provide vitamin B12 unbound to protein even in the absence of IF, absorption can still occur. PA has an insidious onset with non-descript signs and symptoms including fatigue, weakness, headaches, lack of concentration, paresthesias, and digestive disturbance, making it challenging, but important to diagnose early (O’Leary 2010). Patients with PA should be given supplemental doses of at least 500-1000mcg (O’Leary 2010). Several studies investigating the merits of intramuscular, parenteral, and oral administration routes of vitamin B12 have concluded that in the short term, oral supplementation is equally as 68 www.ihpmagazine.com l November / December 2013

effective as other routes in cases of pernicious anemia and malabsoprtion (Seal 2002). Complicating the implications of study results is the common use of the cyanocobalamin form of vitamin B12 (hydroxy, and methyl are available commercially and used clinically), variety in dosing regimens, and unclear long-term comparisons of administration routes. Although cost of oral supplementation is significantly less than IM or parenteral, both IM and parenteral may be more effective in cases where compliance is an issue (Drug and Therapeutics Bulletin 2009). Establishing parameters to measure B12 deficiency is not straightforward. Traditionally the lower limit of reference ranges for serum B12 reflected the level at which megaloblastic anemia normally presented (O’Leary 2010). While serum testing of total vitamin B12 is available and regularly used, it may misrepresent vitamin B12 status as it includes B12 in the form of hepatocorrin, which is biologically unavailable (Green 2011). More recently holotranscobolamin II, the available form of vitamin B12, has been recognized as a useful measure of B12 status (Green 2011). Measurements of other metabolic markers of vitamin B12 status are helpful in determining not only vitamin B12 status, but also differentiating vitamin B12 and folate deficiencies. Elevated levels of both homocysteine and methylmalonic acid are regularly noted in B12 deficiency, while homocysteine elevation with normal methylmalonic acid levels are more common in folate deficiency, although both markers may be elevated with normal B12 and folate status (Green 2011). Vitamin B12 deficiency is a risk factor for anemia and routine screening of haematological markers along with serum vitamin B12, homocysteine, and methylmalonic acid should be evaluated in individuals at risk of B12 deficiency, specifically elderly and vegetarian populations. Additionally, appropriate identification of PA is crucial in preventing serious long-term consequences. There is insufficient evidence to establish the best long term route of administration for B12, although oral, intramuscular, and parenteral administration appear to be equivocal in the short-term.

Cardiovascular Health

Many prospective intervention studies have examined the role of vitamin B12 in cardiovascular disease. Unfortunately, there have been a number of limitations to these trials, including inadequate treatment with vitamin B12 and confounding effects from other simultaneous treatments (Righetti 2009). One recent systematic review of cohort studies included seven studies with varying populations, length of follow-up, study outcomes, and data analysis (Rafnsson 2011). Only one high-quality study reported that low B12 increased the risk of incident cerebral ischaemia. After

The Journal of IHP controlling for homocysteine, the association persisted although weakened, suggesting that the effects of low B12 were only partly mediated by homocysteine. In two studies, higher B12 levels were associated with a greater risk of total mortality and combined fatal and non-fatal coronary events (Rafnsson 2011). In examining other trials that were excluded from the aforementioned systematic review, there are two that stand out. The first is the Vitamin Intervention for Stroke Prevention Trial (Spence 2007). In the original interpretation of the trial, it was shown that vitamin therapy (B12, B6, folate) had no benefit for homocysteine lowering. However, there were problems with the trial, including the lack of a placebo control, the use of a multiple vitamin with low doses of vitamins, patients in both arms of the trial received injections of B12, and folate fortification of grain products in North America coincided with the initiation of the trial. Upon further interpretation of a subgroup from which patients who could not have responded to the study treatment were excluded, there was a significant reduction of stroke, coronary events, and death. When stratified by median entry level of B12, serum B12 status was the key determinant of response, with those with high serum B12 at entry who received high-dose vitamin (0.4mg cyano-cobalamin was considered the high-dose) had a 33% reduction of events compared to those with low B12 who received low-dose vitamins (Spence 2007). The second trial of interest is the Heart Outcomes Prevention Evaluation 2 Trial (Lonn 2006). In this trial, they evaluated whether long-term therapy with folic acid 2.5mg and vitamins B6 50mg and B12 1mg reduced the risk of major cardiovascular events in a high-risk population. The results showed a 25% significant reduction of stroke with vitamin therapy (p = 0.03), but the authors considered this a chance finding (Lonn 2006). Overall, the totality of evidence is unclear as to the independent impact of vitamin B12 in relation to cardiovascular risk. It is also difficult to make large generalizations based on studies with a range of doses, with limited experimental evidence available for supplemental doses above 1mg of B12.

Depression

Low levels of vitamin B12 have been measured in patients with depressive disorders and in some studies, women with metabolically significant deficiencies have been found to have a two-fold higher risk of depression (Penninx 2000). Although many studies examine both folate and vitamin B12, one study has suggested B12 deficiency is independently related to depressive disorders (Tiemeier 2002). A separate study conducted with outpatients diagnosed with major depressive disorder looked at vitamin B12 levels and the consequent six-month treatment outcomes (Hintikka 2003). The

authors examined haematological indices, including erythrocyte folate and serum vitamin B12 levels. The study included 115 outpatients with DSM-III-R major depressive disorder at baseline. The 17-item Hamilton Depression Rating Scale was compiled. The results showed that higher vitamin B12 levels were significantly associated with a better outcome at six-months (Hintikka 2003). More recently, a Finnish population-based study examined the association between vitamin B12 levels and melancholic depressive symptoms (Seppala 2013). Subjects were randomly selected from the National Population Register as part of the Finnish diabetes prevention program and the study consisted of 2806 participants. Health examinations were carried out and depressive symptoms were based on the Beck Depression Inventory. Groups were further divided by melancholic or non-melancholic subgroups based on the DSM-IV. The results showed that the mean vitamin B12 level was associated with melancholic depressive symptoms (Seppala 2013). Many case studies have reported that supplemental vitamin B12 and folic acid can improve the symptoms of depression (Mitchell 2007). In this study, a sample of 12 outpatients with dysthymic disorder was supplemented with 800mcg of folic acid and 1000mcg of vitamin B12 for six weeks. Two instruments were used to measure depressive symptoms: the Beck Depression InventoryII and the Symptom Checklist-90-Revised. At the end of the six weeks, the raw and t-scores of each of the participants indicated a reduction in the reported levels of symptoms of depression (Mitchell 2007). One large study examined the effects of dietary intake of vitamin B6, folate, and vitamin B12 on depressive symptoms (Skarupski 2010). The study sample consisted of 3503 adults aged over 65 years from the Chicago Health and Aging project. Dietary assessment was made by foodfrequency questionnaire and incident depression was measured by the presence of at least four depressive symptoms from the 10-item version of the Center for Epidemiologic Studies Depression scale. The results showed that the higher total intakes of vitamin B6 and B12 were associated with a decreased likelihood of depression for up to 12 years of follow-up, after adjustments were made, including for antidepressant medication use. Each 10 additional milligrams of vitamin B6 and 10 additional micrograms of vitamin B12 were associated with 2% lower odds of depressive symptoms per year (Skarupski 2010). Finally, the B-VITAGE trial is a double-blind, placebo-controlled, randomized trial of homocysteine lowering treatment of depression in later life that is currently in progress (Ford 2010). Participants will receive daily citalopram (20-40mg), plus vitamin B12 (0.4mg), B6 (25mg), and folic acid (2mg) compared to citalopram plus placebo. Over the course of 52 weeks, depressive symptoms will be measured using validated November / December 2013 l www.ihpmagazine.com 69

questionnaires. This trial will clarify whether the systematic use of B-vitamins improve the response of older adults to standard antidepressant treatment. Although teasing out the specific effects of vitamin B12 is difficult, the evidence that is available suggests it is both a safe and effective option in the treatment of depressive symptoms.

Cognitive Decline and Alzheimer Disease

Vitamin B12 deficiency and elevations in associated biomarkers of low vitamin B12 status, are associated with cognitive decline (CD) (Riggs 1996), including Alzheimer Disease (AD) (Wang 2001). The mechanism implicated in the relationship between Vitamin B12 status and CD is the homocysteine lowering effect of B12 (Werder 2010). Studies have shown that in individuals with elevated homocysteine levels and CD, reducing homocysteine through therapies including combinations of folate, vitamin B12, and vitamin B6, has a favourable benefit on cognitive function (Nilsson 2001). Results of RCTs evaluating vitamin B12 supplementation as a treatment for CD and AD are mixed (Malouf 2003). Although a number of RCTs are available, due to small sample size and poor study design, a large number do not provide significant power with which to draw conclusions (Malouf 2003). Factors including dose and duration of treatment, extent and duration of cognitive decline, homocysteine levels, vitamin B12 status (and laboratory techniques used for evaluation), all confound results. A 2003 Cochrane review included only two RCTs evaluating vitamin B12 supplementation in the treatment of CD and AD, and concluded insufficient evidence of efficacy, primarily due to small trial size (Malouf 2003). Several newer studies demonstrate positive outcomes with supplemental B12 (0.5mg) in CD, with the largest effect in individuals with elevated homocysteine levels and with the shortest duration of cognitive decline (De Jager 2013). Additionally, studies have demonstrated a decrease in accelerated brain atrophy in both AD (Douaud 2013) and mild CD with homocysteine-lowering therapy by vitamin B12, folate and vitamin B6 (Smith 2010). Supplemental B12 in combination with folate also shows benefit in as a preventative therapy in decreasing cognitive decline in older individuals with depressive disorders. A 2012 RCT showed significant improvement in cognitive measures after 24 months of supplementation of Vitamin B12 (100mcg) and folate in individuals over 60 (Walker 2012). Of note, in combination therapy with folate, one RCT showed no statistically significant improvement in CD with supplementation, which was likely due to the inclusion of individuals with low or normal homocysteine levels, suggesting lowering homocysteine below normal levels is of no benefit in CD (Pratico 2009). Although there is conflicting evidence represented in research regarding vitamin B12 supplementation in the treatment of CD and AD, there is significant evidence that supplementation in individuals with elevated homocysteine levels early in CD is effective (Walker 2012). Based on the relative safety of vitamin B12 administration and possible degree of benefit, homocysteine and vitamin B12 70 www.ihpmagazine.com l November / December 2013

levels should be routinely checked in individuals with cognitive decline and vitamin B12 (along with folate and vitamin B6) considered as a viable treatment option to lower homocysteine and improve markers of mild CD and AD.

Conclusion

Supplemental vitamin B12 is overwhelmingly safe and no toxic effects have been encountered, especially at doses at or below 1000mcg. Regarding optimal route of administration, there is insufficient evidence to establish the best long term option, but oral, intramuscular, and parenteral administration are all adequate in the short-term. It is imperative to detect vitamin B12 deficiency in those at risk, especially the elderly. Vitamin B12 is an effective treatment for anemia in these cases. Despite some promising results, the totality of evidence is unclear as to the independent impact of vitamin B12 in relation to cardiovascular risk. Vitamin B12 is effective in treating the symptoms of depression, as shown by improvements in various validated questionnaires. Additional well-designed trials are currently in progress. Finally, earlier studies on CD and AD had small sample sizes and poor designs, but newer trials have shown that B12 supplementation in individuals with elevated homocysteine levels early in CD is effective, even in small doses.

References Annibale B, Lahner E, Fave GD. Diagnosis and Management of Pernicious Anemia. Curr Gastroenterol Rep. 2011;13(6):518–24. Carmel, R. Mild transcobalamin I (haptocorrin) deficiency and low serum cobalamin concentrations. Clin Chem. 2003, 49(8):1367-74. Chatthanawaree W. Biomarkers of cobalamin (vitamin B12) deficiency and its application. J Nutr Health Aging. 2011;15(3):227–31. De Jager C a, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry. 2012;27(6):592–600. Douaud G, Refsum H, De Jager C a, Jacoby R, Nichols TE, Smith SM, Smith AD. Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. 20418; 2013;110(23):9523–8. Drug and Therapeutics Bulletin. Oral or intramuscular vitamin B 12? DTB BMJ. 2009;47(2):19–21. Food and Nutrition Board. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington, DC: National Academy Press, 1998. Ford AH, Flicker L, McCaul K, van Bockxmeer F, Hegarty S, Hirani V, Fenner S, Almeida OP. The B-VITAGE trial: a randomized trial of homocysteine lowering treatment of depression in later life. Trials. 2010;11:8

The Journal of IHP Green R. Indicators for assessing folate and vitamin B 12 status and for monitoring the efficacy of intervention strategies. Am J Clin Nutr. 2011;94(suppl):666S–72S.

Righetti M. Protective effect of vitamin B therapy on bone and cardiovascular disease. Recent Pat Cardiovasc Drug Discov. 2009;4(1):37-44

Herrmann W, Schorr H, Obeid R, Geisel J. Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Am J clin Nutr 2003;78:131-6

Riggs KM, Spiro A, Tucker K, Rush D. Relations of vitamin B-12 , vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study. Am J Clin Nutr. 1996;63(3):306–14.

Lonn E, Held C, Arnold JM, Probstfield J, McQueen M, Micks M, Pogue J, Sheridan P, Bosch J, Genest J, Yusuf S, HOPE-2 Investigators. Rationale, design and baseline characteristics of a large, simple, randomized trial of combined folic acid and vitamins B6 and B12 in high risk patients: the Heart Outcomes Prevention Evaluation (HOPE)-2 trial. Can J Cardiol. 2006; 22(1):47-53 Malouf R, Areosa Sastre A. Vitamin B12 for Cognition. Cochrane Database Syst Rev 2003;3. Mazokopakis EE, Starakis IK. Recommendations for diagnosis and management of metformin-induced vitamin B12 (Cbl) deficiency. Diabetes Res Clin Pr. 2012; 97(3):359–67. Mitchell JA. The Effect of Folic Acid and B12 on Depression: Twelve Case Studies. J Orthomolecular Med. 2007;22(4):183-192 O’Leary F, Samman S. Vitamin B12 in health and disease. Nutrients. 2010;2(3):299–316. Nilsson K, Gustafson L, Hultberg B. Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine. Int J Geriatr Psychiatry. 2001;16(6):609–14.

Seal E, Metz J, Flicker L, Melny J. Oral Vitamin B 12 Supplementation in Older Patients with Subnormal or Borderline Serum Vitamin B 12 Concentrations. J Am Geriatr Soc. 2002;50:146–51. Seppala J, Koponen H, Kautiainen H, Eriksson JG, Kampman O, Leiviska J, Mannisto S, Mantyselka P, Oksa H, Ovaskainen Y, Viikki M, Vanhala M, Seppala J. Association between vitamin b 12 levels and melancholic depressive symptoms: a Finnish population-based study. BMC Psychiatry. 2013;13(1):145. Skarupski KA, Tagney C, Li H, Ouyang B, Evans DA, Morris MC. Longitudinal association of vitamin B-6, folate, and vitamin B-12 with depressive symptoms among older adults over time. Amer J Clin Nutr. 2010;92(2):330-5 Smith DA, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, Oulhaj A, Bradley KM, Jacoby R, Refsum H. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PloS One. 2010;5(9):e12244. Spence JD. Perspective on the efficacy analysis of the Vitamin Intervention for Stroke Prevention trial. Clin Chem Lab Med 2007;45(12):1582-5.

Pang WW, Schrier SL. Anemia in the elderly. Curr Opin Hematol. 2012;19(3):133–40.

Stabler SP. Clinical practice. Vitamin B12 deficiency. New Engl J Med. 2013;368(2):149–60.

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Pawlak R, Parrott SJ, Raj S, Cullum-Dugan D, Lucus D. How prevalent is vitamin B(12) deficiency among vegetarians? Nutr Rev. 2013;71(2):110–7.

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Walker JG, Batterham PJ, Mackinnon AJ, Jorm AF, Hickie I, Fenech M, Kljakovic M, Crisp D, Christensen H. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms — the Beyond Ageing Project: a randomized controlled trial. Amer J Clin Nutr. 2012;95(1):194–203.

Pratico D. High-dose vitamin supplements and Alzheimer disease. JAMA. 2009;301(10):1020–1. Rafnsson SB, Saravanan P, Bhopal RS, Yajnik CS. Is a low blood level of vitamin B12 a cardiovascular and diabetes risk factor? A systematic review of cohort studies. Eur J Nutr 2011;50:97-106

Wang H, Wahlin Å, Basun H, Fastbom J. Vitamin B 12 and folate in relation to the development of Alzheimer’s disease. Neurology. 2001; 56(9);1188-94. Werder SF. Cobalamin deficiency, hyperhomocysteinemia, and dementia. Neuropsychiatr Dis Treat. 2010;6:159–95. November / December 2013 l www.ihpmagazine.com 71

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.

Leah Gillingham, MSc, PhD Chief Scientific Officer, Nutritional Fundamentals for Health (NFH) 14 Kings Court, Bath, Ontario K0H 1G0 Ph: 613-876-7114 Email:Â leah@nfh.ca

The metabolic fate of alpha linolenic acid (ALA) Extremely limited conversion efficiency By Leah Gillingham, MSc, PhD

72 www.ihpmagazine.com l November / December 2013

TheThe Journal Journal of IHP of IHP – Continuing – Continuing Education Education ABSTRACT: EPA and DHA possess important physiological and biological properties in human health and development; however, it is alpha-linolenic acid (ALA) that is classified as the essential n-3 PUFA. While humans have the required enzymes to biosynthesize omega-3 long-chain polyunsaturated fatty acids (PUFA), studies demonstrate that the majority of ALA is β-oxidized and only ~5% of ALA is converted to eicosapentaenoic acid (EPA) and <0.5% of ALA is converted to docosahexaenoic acid (DHA). Even very high intakes of dietary ALA fail to effectively modulate plasma and tissue levels of DHA. Furthermore, the abundance of linoleic acid (LA) in our diet, as well as age, gender and genetics influence the conversion efficiency of ALA. Therefore, direct dietary consumption or supplementation of EPA and DHA from fish, fish oil, or algae is the only clinically effective way to increase blood and tissue levels of these longchain PUFA in humans for optimal health and disease prevention.

INTRODUCTION

Considerable clinical interest has focused on the health benefits of omega-3 polyunsaturated fatty acids (ω-3 PUFA). While consumption of marine derived eicosapentaenoic acid (EPA; 20:5ω-3) and docosahexaenoic acid (DHA; 22:6ω-3) have been evidenced to prevent cardiovascular and neurological disease risk, the specific function of plant derived alpha-linolenic acid (ALA; 18:3ω-3) remains a matter of debate. EPA and DHA play a vital role in cellular membranes, maintaining fluidity, protein and cellular functions, as well as influencing eicosanoid metabolism, gene expression and cell signaling (Adkins 2010). However, the specific bioactive role of ALA is unclear (Sinclair 2002). It has been suggested that the major function of ALA is to serve as a precursor for EPA and DHA, a pathway that has received much attention and clinical investigation. In 1929, Burr and Burr first identified the nutritional essentiality of LA, and later ALA (Burr 1929, Burr 1930). ALA is the parent ω-3 PUFA containing three double bonds with the first double bond located at

the third carbon relative to the methyl end of the 18-carbon chain. ALA and ω-6 linoleic acid (LA, 18:2ω-6) are termed essential fatty acids because humans lack the delta (Δ)15- and Δ12-desaturase enzymes required for insertion of a double bond at the ω-3 or ω-6 position, respectively. Since EPA and DHA can be synthesized from ALA via a series of alternating desaturation and elongation steps, these long-chain PUFA are not considered essential. However, whether endogenous synthesis of EPA and DHA from ALA is adequate to support growth, physiological needs, and disease risk reduction is questioned (Harris 2009, Saldanha 2009). Considering negligible plasma and tissue levels of ALA, yet its classification of essential, this review will examine the biosynthesis of EPA and DHA from ALA, factors influencing ALA metabolism, and ω-3 PUFA in the current diet.

BIOSYNTHESIS OF LONG-CHAIN POLYUNSATURATED FATTY ACIDS

The predominate site of ALA desaturation and elongation occurs in the liver, however, also occurs to a lesser extent in other tissues, including the brain and heart (Cho 1999 A, Cho 1999 B). Dietary LA and ALA compete for the same desaturase and elongase enzymes for long-chain PUFA biosynthesis with the majority of this pathway occurring in the endoplasmic reticulum. Of interest, the desaturase enzymes have a higher affinity for ALA versus LA (Plourde 2007), however, high levels of dietary LA saturate Δ6-desaturation inhibiting the accumulation of ω-3 long-chain PUFA, namely EPA (Angela Liou 2009, Liou 2007). The first reaction in the conversion pathway is the desaturation of ALA to stearidonic acid (SDA; 18:4ω-3) or LA to gamma-linolenic acid (GLA; 18:3ω-6) via the rate-limiting enzyme Δ6-desaturase (Sprecher 2000) (Figure 1). Next, elongation and Δ5-desaturation converts SDA to EPA and GLA to arachidonic acid (AA; 20:4ω-6), the major bioactive n-6 PUFA in tissue membranes and precursor for proinflammatory eicosanoids (Adkins 2010). Compared to AA, EPA is quantitatively a minor fatty acid in tissue membranes and undergoes further elongation to docosapentaenoic acid (DPA; 22:5ω3), or is metabolized by cyclooxygenase (COX) and lipoxygenase (LOX) enzymes in the synthesis of anti-inflammatory eicosanoids. In humans, DPA undergoes another elongation and Δ6-desaturation step, and then partial β-oxidation in the peroxisome to form DHA (Sprecher 2000). Structurally, DHA is the predominant ω-3 PUFA esterified into tissue membrane phospholipids. DHA can also be

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metabolized to produce resolvins and protectins in the resolution of inflammation (Adkins 2010). It has been hypothesized that multiple use of the rate-limiting Δ6desaturase enzyme for the conversion of ALA to SDA and 24:5n-3 to 24:6n-3 may lead to a “bottle-neck” in the metabolic pathway and an associated decrease in the synthesis of DHA (D’andrea 2002, Kitson 2010). Another possible rate-limiting step may be related to the compartmental translocation of 24:6n-3 from the endoplasmic reticulum to the peroxisome. Both hypotheses demand further investigation.

RESULTS FROM HUMAN STUDIES:

The conversion of ALA to long-chain ω-3 PUFA is very inefficient. Dietary supplementation and isotope tracer studies in humans demonstrate a direct linear relationship between dietary ALA and plasma and tissue concentrations of EPA, at approximately 5% conversion efficiency (Plourde 2007). However, biosynthesis of DHA is negligible with typically less than 0.5% conversion of ALA to DHA. Human studies supplementing ALA ranging from 1.5 to 40 g/ day for a minimum of three weeks report a relative increase in phospholipid concentration of EPA ranging from trace levels to 250% (Plourde 2007). Studies have also observed an increase in plasma and tissue concentrations of DPA, although to a lesser extent than EPA concentrations. However, the majority of dietary ALA intervention studies fail to effectively modulate plasma and tissue levels of DHA. Gillingham et al demonstrated that consuming 20 g/day of ALA from a flaxseed oil supplemented diet (~2.5 tbsp flaxseed oil daily) resulted in a relative 222% increase in plasma EPA concentration (1.74% total fatty acids) compared with control (0.54% total fatty acids) (2011). However, DHA concentration did not change after supplementing with flaxseed oil. Similarly, supplementing lactating women with 20 g/day of flaxseed oil (10.7 g/day ALA) for four weeks increased breast milk EPA and DPA, but not DHA concentrations (Francois 2003). Additionally, very high levels of dietary ALA, as well as LA, may saturate the Δ6-desaturase enzyme further inhibiting the final steps of Δ6-desaturation of 24:5n-3 to DHA (Gibson 2011). Even with vegetarian and vegan diets, ALA conversion to DHA is not up-regulated (Fokkema 2000, Li 1999). James et al revealed that compared to dietary ALA, supplementing with SDAenriched vegetable oil (therefore, bypassing the first Δ6desaturase rate-limiting step) more effectively increased plasma and tissue concentrations of EPA, however, did not raise DHA concentrations (2003). In addition, EPA supplementation does not significantly elevate DHA concentrations (Brenna 2009). Therefore, the only effective way to increase tissue DHA concentrations is through its direct consumption. 74 www.ihpmagazine.com l November / December 2013

FACTORS AFFECTING EPA AND DHA BIOSYNTHESIS FROM ALA

DIETARY Ω-6 LINOLEIC ACID CONTENT: The abundance of LA and resulting high ω-6 to ω-3 PUFA ratio in current Western diets significantly impedes the conversion efficiency of ALA. Liou and collegues demonstrated that while maintaining dietary ALA at 1% energy, increasing levels of dietary LA from 4% to 10% energy, thus varying the ω-6 to ω-3 PUFA ratio from 4:1 to 10:1, resulted in a decrease in plasma EPA concentrations in healthy men (Angela Liou 2009, Liou 2007). In another human dietary intervention study, lowering the ω-6 to ω-3 PUFA ratio resulted in a significant decrease in platelet aggregation (Freese 1994). Furthermore, trans fats rich in hydrogenated vegetable oils inhibit the synthesis of ω-3 long-chain PUFA (Kummerow 2004). MICRONUTRIENTS: Vitamins B3, B6, and C, magnesium and zinc are important cofactors to the Δ5and Δ6-desaturase enzymes. Therefore, low intakes of these essential micronutrients may lead to a reduction in the synthesis of ω-3 long-chain PUFA (Cunnane 1988, de Lorgeril 2005, Harris 2009). GENDER: Gender may affect biosynthesis of long-chain PUFA, as DHA concentration of plasma phospholipids have been shown to be higher in women than in men (Decsi 2011). Giltay et al observed a 15% increase in DHA status in women compared with men (2004). Furthermore, administration of oral estradiol increased DHA status by 42%, while testosterone decreased DHA status by 22%. It is proposed that estrogen may upregulate ALA metabolism to DHA, and thus, increase maternal DHA status particularly during pregnancy due to the greater demand of DHA for fetal neurological development (Otto 2001, Innis 2000).

AGE: Studies suggest that infants exhibit increased conversion of ALA to long-chain PUFA, including DHA (Clark 1992, Jensen 1996). A study tracing ALA metabolism in preterm infants fed long-chain PUFA enriched formula reported that in one-month old infants about 42% of ALA was converted to DHA, whereas only 11% was converted at three-months of age, and 7% at seven months of age (Carnielli 2007). Typically, conversion of ALA to DHA is still limited in healthy infants at ~1% (Brenna 2009). However, differences in adult age (18–29 versus 45–69 years) have not been shown to influence metabolism of ALA to EPA or DHA (Patenaude 2009). GENETICS: Fatty acid desaturase genes FADS1 and FADS2 encode for Δ5-desaturase and Δ6-desaturase, respectively (Cho 1999, Cho 1999). Schaeffer and colleagues published the first study reporting that single nucleotide polymorhpisms (SNP) of the FADS1/ FADS2 gene cluster modulate ALA and LA metabolism

The Journal of IHP – Continuing Education leading to differences in phospholipid PUFA concentrations (2006). More specifically, minor allele carriers for SNPs located in the FADS1/ FADS2 gene cluster have reduced ability to convert LA to AA (Tanaka 2009) or ALA to EPA (Gillingham 2013a). Of interest, genetic variation explains ~40% or more of the interindividual variability in all fatty acid concentrations (Lemaitre 2008). Martinelli et al reported that individuals carrying FADS polymorphisms, associated with higher conversion of LA to AA, have increased proinflammatory CRP concentrations and risk for coronary artery disease (2008).

approximately 80 and 50 mg/day, respectively (Denomme 2005, Rhodes 2012). In addition, biosynthesis of long-chain PUFA, namely DHA from dietary ALA is insufficient to meet target recommended intakes of EPA and DHA for optimal health and disease prevention.

OTHER METABOLIC PATHWAYS

SAFETY OF EPA AND DHA SUPPLEMENTATION

β-oxidation accounts for the major metabolic fate of dietary ALA (McCloy 2004). McCloy et al. demonstrated that ~71% of dietary ALA was oxidized over a seven day period, the highest oxidation rate of all fatty acids (2004). During mitochondrial β-oxidation of ALA, carbon units generated in the form of acetyl-CoA can be recycled to synthesize SFA, MUFA, cholesterol and ketone bodies (Burdge 2003). Second to β-oxidation, storage of ALA in adipose tissues accounts for a main metabolic route of dietary ALA (McCloy 2004), however, ALA is readily mobilized from fatty acid tissue during increased energy demands of the body.

DIETARY OMEGA-3 POLYUNSATURATED FAT INTAKE AND RECOMMENDATIONS

Since ALA and LA are the only fatty acids classified as essential, the US Institute of Medicine’s (IOM) Food and Nutrition Board, together with Health Canada, has established an Adequate Intake (AI, an intake level necessary to achieve nutritional adequacy and prevent deficiency symptoms) for ALA as 1.1-1.6 g/day and for LA as 12-17 g/day for adults (Institute of Medicine 2002). Symptoms of ALA and LA deficiency include scaly dry skin, reproductive failure, numbness, weakness, pain, and blurred vision (Collins 1971, Holman 1982). However, current Western intake of ALA at 1.4-1.8 g/day and LA at 13-18 g/day by adults (Rhodes 2012) exceed the outlined AI by the IOM. The clinical concern is that current intake of combined EPA and DHA at 90–120 mg/day fail to meet recommendations outlined by professional health organization ranging from 500–4000 mg/ day (Table 1). Due to the importance of DHA in fetal retina and brain growth and development, the minimum recommended intake of DHA during pregnancy and lactation is 200 mg/day (Koletzko 2007). However, pregnant and lactating women in Canada and the United States only consume

The FAO/WHO joint committee recommends an ω-6 to ω-3 ratio between 5:1 and 10:1 (WHO/FAO 1995). Of interest, the Paleolithic diet contained an ω-6 to ω-3 ratio of <1:1 (Kuipers 2010), while current intakes range from 10-25:1 in the North America diet.

In 1997, the US Food and Drug Administration (FDA) granted Generally Recognized As Safe (GRAS) status to refined fish oils and indicated that the consumption of up to 3g/day of EPA+DHA is considered safe for the adults population, including patients with diabetes, bleeding tendencies, and elevated LDL-cholesterol (1997). Intake exceeding 3g/day should only be recommended under the guidance of a healthcare practitioner.

DIETARY SOURCES:

ω-6 LA is abundant in our diet, rich in corn, safflower, soybean, and sunflower oils. However, ω-3 ALA is found in only a limited amount of foods, namely flaxseed, walnuts, soybean and their oils, as well as canola oil, butternuts, and chia seeds. Although flaxseed oil represents the richest source of ALA (7.3 g ALA/tbsp), it is not commonly consumed compared with soybean oil (0.9 g ALA/tbsp) and canola oil (1.3 g ALA/ tbsp) (USDA 2011). Purslane, a wild leafy vegetable common in the Eastern Mediterranean diet, contains 300–400mg ALA/100g serving (Simopoulos 1996). EPA and DHA are primarily found in fish, fish oil, krill oil or algae. However, the concentration of EPA and DHA substantially varies in fish species (Table 2). For example, fatty fish such as farmed Atlantic salmon provides 1.83 g EPA+DHA per 3 oz serving, whereas the same amount of lean fish such as cod provides only 0.14 g EPA+DHA (USDA 2011). Therefore, one would have to consume approximately four servings of farmed Atlantic salmon or 52 servings of cod per week to achieve a recommended intake of 1g/day (Table 2). Where fatty fish intake exceeds two servings per day, such as Greenland and Japan (Stark 2002, Iso H 1989), plasma EPA/DHA levels are in what is widely considered a therapeutic range (Harris 2010). However, in most parts of the world, these November / December 2013 l www.ihpmagazine.com 75

levels are not being achieved. In addition, depending on the species of fish, excessive fish intake may lead to concerns surrounding mercury exposure, particularly in pregnancy (Koletzko 2007). Taken together, fish oil supplements may provide a more feasible option to target clinical recommendations for EPA+DHA. Minor amounts of EPA can also be found in seaweed, such as kelp, laver, and wakame ranging in EPA levels from 0.004 to 0.186 g/100g serving (USDA 2011). Additionally, microalgaebased supplements offer an alternative for DHA intakes for vegetarians/vegans.

CONCLUSION

The consensus of human clinical trials substantiate that the biosynthesis of EPA and DHA from dietary ALA is extremely limited and insufficient to meet protective tissue levels for disease prevention. In addition, factors including diet, gender, age and genetics affect individual’s capacity for biosynthesis and resulting EPA and DHA tissue concentration. Considering the majority of dietary ALA is β-oxidized, negligible conversion rates, and low intakes of EPA and DHA in the current diet, professional organizations emphasize direct supplementation of EPA and DHA in the diet for optimal health and disease risk reduction.

Figure 1: Metabolism of omega-3 and omega-6 essential fatty acids.

Population Healthy adults Healthy adults Vegetarian & Vegan Diets Vegetarian & Pregnancy & Vegan Diets Pregnancy Lactation & Lactation Cardiovascular patients Hypertriglyceridemic patients Neurological Neurological health health Inflammation (i.e. rheumatoid arthritis)

Target 1o Prevention of disease (i.e. CVD) 1o Prevention of disease (i.e. CVD) 1o Prevention of disease (i.e. CVD) o 1 Prevention of disease (i.e. CVD) Fetal growth and development Fetal growth and development 2o CVD Prevention 2o CVD Prevention Reduction in blood TAG levels Depressive Reduction inrelated blood disorders TAG levels Pain management Depressive related disorders Pain management

Dose Dose 500 500mg/d mg/dEPA+DHA EPA+DHA 2-4 g/d ALA + 2-4 g/d ALA + 100-300 mg/d DHA 100-300 mg/d DHA ≥200mg/d mg/dDHA DHA (can contain EPA) ≥200 ~1 g/d EPA+DHA (can contain EPA) 2–4g/d g/dEPA+DHA EPA+DHA ~1 2–4 ≥ 1 g/d EPA+DHA EPA (can contain DHA) ≥~3 1 g/d g/d EPA EPA+DHA (can contain DHA) ~3 g/d EPA+DHA

Table 1: Dietary recommendations for omega-3 fatty acids in health and disease.

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Reference Kris-Etherton 2007 Davis 2003 Koletzko 2007 Kris-Etherton 2003 Miller 2011 Martins 2012 / Peet 2005 Kremer 2000 / Calder 2006

The Journal of IHP – Continuing Education Dietary source EPA+DHA Amount needed to meet 1000 mg Mean mercury mg/serving EPA+DHA/day concentration servings/week* ppm Finfis Tuna – Light, canned 230 30 0.128 Tuna – White (albacore), canned 733 10 0.350 Salmon – Sockeye 673 10 0.022 Salmon – Atlantic, farmed 1825 4 0.022 Salmon – Atlantic, wild 1564 5 0.022 Mackerel – King 341 21 0.730 Mackerel – Pacific 1571 5 0.088 Herring – Pacific 1807 4 0.084 Trout – Rainbow, farmed 744 9 0.071 Trout – Rainbow, wild 840 8 0.071 Halibut – Atlantic & Pacific 200 35 0.241 Cod – Atlantic & Pacific 135 52 0.111 Shellfish Shrimp – Mixed species 235 30 0.009 Crab – Alaskan King 351 20 0.065 Lobster – Mixed species 408 17 0.093 Supplements Cod liver oil 180 39 ND Standard fish body oil 300 23 ND Specialty concentrate 600 12 ND Pharmaceutical concentrate (Lovaza®) 840 8 ND Table 2: Amount of EPA and DHA in selected fish/shellfish and fish oil supplements and approximate servings required per week to provide 1000 mg of EPA+DHA per day.

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The Journal of IHP – Continuing Education Association and Dietitians of Canada: dietary fatty acids. J Am Diet Assoc. 2007 Sep;107(9):1599-611. Kuipers RS, Luxwolda MF, Dijck-Brouwer DA, Eaton SB, Crawford MA, Cordain L, Muskiet FA. Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet. Br J Nutr. 2010 Dec;104(11):1666-87. Kummerow FA, Zhou Q, Mahfouz MM, Smiricky MR, Grieshop CM, Schaeffer DJ. Trans fatty acids in hydrogenated fat inhibited the synthesis of the polyunsaturated fatty acids in the phospholipid of arterial cells. Life Sci. 2004 Apr;74(22):2707-23. Lemaitre RN, Siscovick DS, Berry EM, Kark JD, Friedlander Y. Familial aggregation of red blood cell membrane fatty acid composition: the Kibbutzim Family Study. Metabolism. 2008 May;57(5):662-8. Li D, Sinclair A, Wilson A, Nakkote S, Kelly F, Abedin L, Mann N, Turner A. Effect of dietary alpha-linolenic acid on thrombotic risk factors in vegetarian men. Am J Clin Nutr. 1999 May;69(5):872-82. Liou YA, King DJ, Zibrik D, Innis SM. Decreasing linoleic acid with constant alpha-linolenic acid in dietary fats increases (n-3) eicosapentaenoic acid in plasma phospholipids in healthy men. J Nutr. 2007 Apr;137(4):945-52. Martinelli N, Girelli D, Malerba G, Guarini P, Illig T, Trabetti E, Sandri M, Friso S, Pizzolo F, Schaeffer L, et al. FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease. Am J Clin Nutr. 2008 Oct;88(4):941-9. Martins JG, Bentsen H, Puri BK. Eicosapentaenoic acid appears to be the key omega-3 fatty acid component associated with efficacy in major depressive disorder: a critique of Bloch and Hannestad and updated meta-analysis. Mol Psychiatry. 2012 Dec;17(12):1144-9; discussion 1163-7. McCloy U, Ryan MA, Pencharz PB, Ross RJ, Cunnane SC. A comparison of the metabolism of eighteen-carbon 13C-unsaturated fatty acids in healthy women. J Lipid Res. 2004 Mar;45(3):474-85. Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, KrisEtherton PM, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011 May 24;123(20):2292-333. Otto SJ, van Houwelingen AC, Badart-Smook A, Hornstra G. Changes in the maternal essential fatty acid profile during early pregnancy and the relation of the profile to diet. Am J Clin Nutr. 2001 Feb;73(2):302-7. Patenaude A, Rodriguez-Leyva D, Edel AL, Dibrov E, Dupasquier CM, Austria JA, Richard MN, Chahine MN, Malcolmson LJ, Pierce GN. Bioavailability of alpha-linolenic acid from flaxseed diets as a function of the age of the subject.

Eur J Clin Nutr. 2009 Sep;63(9):1123-9. Peet M, Stokes C. Omega-3 fatty acids in the treatment of psychiatric disorders. Drugs. 2005;65(8):1051-9. Plourde M, Cunnane SC. Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements. Appl Physiol Nutr Metab. 2007 Aug;32(4):619-34. Simopoulos AP, Salem N,Jr. Purslane: a terrestrial source of omega-3 fatty acids. N Engl J Med. 1986 Sep;315(13):83. Stark KD, Mulvad G, Pedersen HS, Park EJ, Dewailly E, Holub BJ. Fatty acid compositions of serum phospholipids of postmenopausal women: a comparison between Greenland Inuit and Canadians before and after supplementation with fish oil. Nutr. 2002 Jul-Aug;18(7-8):627-30. Rhodes, D.G., Clemens, J.C., Goldman, J.D., LaComb, R.P., Moshfegh, A.J. 2012. 2009-2010 What We Eat In America, NHANES Tables 1-36. Worldwide Web Site: Food Surveys Research Group. Retrieved from http://www.ars.usda.gov/ Services/docs.htm?docid=18349 Saldanha LG, Salem N,Jr, Brenna JT. Workshop on DHA as a required nutrient: overview. Prostaglandins Leukot Essent Fatty Acids. 2009 Aug-Sep;81(2-3):233-6. Schaeffer L, Gohlke H, Müller M, Heid IM, Palmer LJ, Kompauer I, Demmelmair H, Illig T, Koletzko B, Heinrich J. Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum Mol Genet. 2006 Jun;15(11):1745-56. Sinclair AJ, Attar–Bashi NM, Li D. What is the role of α–linolenic acid for mammals? Lipids. 2002 Dec;37(12):1113-23. Sprecher H. Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochim Biophys Acta. 2000 Jul;1486(2-3):219-31. Tanaka T, Shen J, Abecasis GR, Kisialiou A, Ordovas JM, Guralnik JM, Singleton A, Bandinelli S, Cherubini A, Arnett D, et al. Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study. PLoS Genet. 2009 Jan;5(1):e1000338. US Food and Drug Administration, Department of Health and Human Services. Substances affirmed as generally recognized as safe: menhaden oil. 1997. Retrieved from http://www.gpo.gov/fdsys/ pkg/FR-1997-06-05/html/97-14683.htm USDA (US Department of Agriculture). National nutrient database 2011. Retrieved from http://www.nal.usda.gov/fnic/ foodcomp/search/ WHO/FAO joint consultation. WHO and FAO joint consultation: fats and oils in human nutrition. Nutr Rev. 1995 Jul;53(7):202-5. November / December 2013 l www.ihpmagazine.com 79

Questions 1. Which of the following is an essential fatty acid? a) alpha linolenic acid (ALA) b) eicosapentanoic acid (EPA) c) docosahexanoic acid (DHA) d) gamma linoleic acid (GLA) 2. Studies show that ALA conversion results in which of the following: a) ~5% of ALA is converted to eicosapentaenoic acid (EPA) b) 10% of ALA is converted to docosahexaenoic acid (DHA) c) under 0.5% of ALA is converted to eicosapentaenoic acid (EPA) d) none of the above 3. Essential fatty acids are known to be critical for neurological and cardiovascular health. In particular, ALA and ω-6 linoleic acid (LA, 18:2ω-6) are termed essential fatty acids because humans lack the delta (Δ)15- and Δ12-desaturase enzymes required for insertion of a double bond at the ω-3 or ω-6 position, respectively. Since EPA and DHA can be synthesized from ALA, they are NOT considered essential. a) True b) False 4. The primary site of ALA desaturation and elongation is the gut, where 90% of conversion occurs. a) True b) False

5. Which is the rate limiting enzyme in the conversion of ALA to EPA? a) Δ5-desaturase b) Δ6-desaturase c) Δ5-elongase d) Δ6-elongase

6. Which of the following is true about DHA? a) it is the predominant ω-3 PUFA esterified into tissue membrane phospholipids; b) it is metabolized to produce resolvins and protectins in the resolution of inflammation; c) it is synthesized from EPA via DPA (docosapentanoic acid) d) all of the above 7. The US Institute of Medicine’s (IOM) and Health Canada have established an Adequate Intake (AI) for ALA as 1.1-1.6 g/ day. There is concern however that this level is not sufficient for production of adequate amounts of EPA and DHA, as recommended by professional organizations. a) True b) False 8. EPA and DHA have a Generally Recognized As Safe (GRAS) status when taken up to 3g per day, including in patients with diabetes, bleeding tendencies, and elevated LDL cholesterol. a) True b) False 9. Potential problems of relying strictly on dietary sources of EPA and DHA include the following: a) Oily fish contain over 1g EPA+DHA per 3oz serving, however white fish may contain only 0.14g; b) Two servings per day are required in order to achieve therapeutic serum levels; c) High levels of fish consumption may lead to excess exposure to heavy metals such as mercury; d) all of the above 10. The following nutrients are cofactors of the Δ5- and Δ6desaturase enzymes: vitamin A, vitamins B3, B6, and C, magnesium and zinc. a) True b) False

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

Area of Clinical Focus:

Size of Practice (# of Doctors): 0-5 5-10 10 & up

Years of Practice:

80 www.ihpmagazine.com l November / December 2013

0-5

5-10

10 & up

PRODUCT MONOGRAPH

omega3+ joy o3mega+ joy o3mega+ joy delivers fish derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in a unique ratio (20:1 EPA: DHA), specifically formulated to address mood and behavior. Specific clinical indications demonstrated to benefit from intervention with Omega-3 oils biased in favor of EPA include depressive disorders (unipolar depression, major depressive disorder, bipolar disorder), schizophrenia, ADD/ ADHD, and others. High EPA Omega-3 fatty acids in adult depressive disorders While controlled human trials examining DHA- based oils in adult depressive disorders typically fail to demonstrate benefit (Grenyer 2007, Llorente 2003), highly significant improvement in depressive symptoms are reproducibly demonstrated upon intervention with EPA- based omega-3 oils (Frangou 2006, Peet 2002a, Zanarini 2003). Most trials of Omega-3 fatty acids in adult depressive disorders utilize the oil adjunctively with conventional medications. A recent meta analytic review (Lin 2007) reported the following; “When pooling the results of 10 included studies, we found a significant antidepressant effect of Omega-3 PUFA’s. Likewise, Omega-3 PUFA’s significantly improved depression in patients with clearly defined depression or with bipolar disorder”. High EPA Omega-3 fatty acids in adult schizophrenia Several controlled human trials have examined the use of Omega-3 fatty acids as adjunctive therapy among patients with schizophrenia. Again, EPA- based oils appear to deliver a significant magnitude of efficacy (modest improvement in negative symptoms, reduction in adverse effects associated with antipsychotic medication use) (Emsley 2006, Peet 2002b, Peet 2001). DHA- based oils have failed to symptomatically benefit schizophrenic individuals (Peet 2001). Omega-3 oils appear to be more effective for individuals with early stages of schizophrenic illness. High EPA Omega-3 fatty acids in childhood depression and ADD/ ADHD EPA- based oils have demonstrated impressive benefit in objective markers of learning, concentration, memory, and overall academic performance in four separate controlled human studies. 40-45% of children administered a high EPA- Omega-3 oil no longer met diagnostic criteria for ADD/ ADHD within 3-6 months of beginning Omega-3 therapy (Johnson 2007, Richardson 2005, Sinn 2007, Sorgi 2007). Studies of DHA- based oils in childhood ADD/ ADHD typically fail to achieve significant benefit (Hiyarama 2004, Voigt 2001). One trial of high EPA- Omega-3 in children with depression has also demonstrated very positive outcomes. 70% of children achieved a greater than 50% reduction in the Children’s Depression Rating Scale (CDRS), and 40% of children met remission criteria (CDRS score <29 at study exit) (Nemets 2006).

Finished Product Specifications

Dosage Based on Controlled Human Trials Adult depressive disorders

Minimum 1000mg EPA per day

Parameter

Adult schizophrenia

Minimum 2000mg EPA per day

Stability

Childhood disorders of mood

400- 600mg EPA per day

and behavior

Test

Method

Peroxide Value (PV)

AOCS Cd 8-53

Max 5meq/kg

p-Anisidine Value (pAV)

AOCS Cd 18-90

Max 20

Total Number

pAV + (2xPV)

Max 26

Arsenic

ICP-MS

<0.14ug/kg BW/day

Cadmium

ICP-MS

<0.09ug/kg BW/day

Lead

ICP-MS

<0.29ug/kg BW/day

Mercury

ICP-MS

<0.29ug/kg BW/day

Total aerobic count

USP <61>

<1x104 CFU/g

Pesticides

HRGC/ HRM

Max 2ppm

References Emsley R. Schizophr Res. 2006;84(1):112-20.

Heavy Metals

Frangou S. Br J Psychiatry. 2006; 188:46-50. Grenyer BF. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(7):1393-6. Hirayama S. Eur J Clin Nutr. 2004;58(3):467-73. Johnson M. Presented at Children and Adults with Attention Deficit/ Hyperactivity Disorder (CHADD), November 7-10, 2007. Washington, DC. Lin PY. J Clin Psychiatry. 2007 Jul;68(7):1056-61.

Purity

Llorente AM. Am J Obstet Gynecol. 2003; 188(5):1348-53. Nemets H. Am J Psychiatry. 2006;163(6): 1098-100. Peet M. Schizophr Res. 2001 Apr 30;49(3): 243-51.

Dioxins PCDDs HRGC/HRMS Max 2pg, WHOand PCDFs PCDD/FTEQ/g

Peet M (a). Arch Gen Psychiatry. 2002 Oct;59(10):913-9. Peet M (b). J Psychiatr Res. 2002 Jan-Feb;36(1):7-18. Richardson AJ. Pediatrics. 2005 May;115(5):1360-6. Sinn N. J Dev Behav Pediatr. 2007 Apr;28(2):82-91. Sorgi PJ. Nutr J. 2007 Jul 13;6(1):16. Voigt RG. J Pediatr. 2001 Aug;139(2) :189-96. Zanarini MC. Am J Psychiatry. 2003 Jan;160(1):167-69.

Tolerances

Potency

PCBs

HRGC/HRMS

EPA

HPLC

DHA

HPLC

Max 0.09ppm Target 500 mg (80-120% label claim) Target 25 mg (80-120% label claim)

Pre Natal SAP PRODUCT MONOGRAPH

Micronutrient status in women of reproductive years is of extreme importance, especially around the time of conception. Micronutrient supplementation is recommended for all women around this time to cover the gap in maternal nutrition and to avoid nutrient deficiency leading to complications of pregnancy and adverse fetal outcomes. Micronutrient status can influence the health of the woman during her pregnancy, the health and development of the fetus, and even years of infancy. Due to the rapid changes in the female body and the demands of the developing fetus, nutritional status is paramount as there are critical windows of development. Nutritional deficiencies during this time can affect the development of the immune system, and have implications to cardiovascular, spinal, musculoskeletal, neurological, and metabolic function. It is always prudent to ensure adequate micronutrient status.

MINERALS

are also risk factors for the development of type 2 diabetes(13) and cardiovascular disease. Supplementing B12 will also help avoid other complications during pregnancy, such as macrocytic anemia and neurological complications affecting sensory and motor function.(14) Folic acid and B12 deficiency can also lead to other pregnancy complications. Higher pregnancy rates are found with micronutrient supplementation in those with and without fertility issues. Previous studies suggest that folic acid status may be important in the ovarian response to FSH and helps to regulate the cycle and that low levels of folate were found to be strongly associated to ovulatory infertility.(15) In age- and energy-adjusted analyses, intakes of vitamins B1, B2, B6, B12, folic acid and niacin were inversely related to the risk of ovulatory infertility.(15) Women with sufficient vitamin B6 showed a higher conception rate and lower risk of early pregnancy loss compared to those with vitamin B6 deficiency.(12)

Iron is essential to blood oxygen-carrying capacity. Iron bisglycinate chelates have been shown to be superior in absorption and bioavailability to other forms of iron.(1, 2, 3) Specifically, iron bioavailability as a glycine chelate was reported to be 3.4 times greater than that of ferrous sulfate,(4) with reduced incidences of side effects including gastric irritation and constipation (33% less). Iron deficiency anemia imposes a risk of hemorrhage during delivery. It is also associated with the risk of preterm delivery. Iron bisglycinate may negate the necessity for its coadministration with vitamin C for absorption, due to substantially increased bioavailability.(5)

Suboptimal vitamin B6 status and elevated plasma concentrations of homocysteine, a marker of poor folic acid and/or vitamin B12 status, also have been associated with increased risk of clinical spontaneous abortion.(12) In addition, numerous studies have documented associations between low vitamin B6 status and inflammatory responses, and inflammation has been linked to early pregnancy loss.(12) B vitamin deficiency coupled with hyperhomocysteinemia are associated with recurrent abortion. B6 has also been shown to decrease nausea and vomiting in pregnancy.

Zinc is essential to human metabolism and catalyzes more than 100 enzymes, facilitates protein folding and regulates gene expression. Zinc deficiency may cause complications during pregnancy and delivery, as well as growth retardation, congenital abnormality, and retarded neurobehavioral and immunological development. Iodine deficiency has an effect on thyroid function and can influence rate of conception, and can lead to cretinism and possible preterm delivery.

Vitamin D is important for the development of bones, and an inadequacy of it can contribute to the development of rickets, a disease once thought to be eradicated. Rickets is once again on the rise as people lather on sunscreen and limit sun exposure due to the damage UV rays can cause. The downside of this is that without direct sunlight exposure, the body cannot synthesize its own vitamin D.

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

ANTIOXIDANTS, BIOFLAVONOIDS, VITAMIN C AND VITAMIN E

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

B VITAMINS AND FOLATE

VITAMIN D

Expecting moms need to ensure adequate intake for both themselves and the fetuses to optimize proper development and strength of fetal bones, and maintenance of their own. The role of vitamin D is to maintain serum levels of minerals such as calcium and phosphorus to support metabolic function, neuromuscular transmission, regulate bone metabolism and enhance immunity. Studies show that at week 28, 100 mg/d of calcium is being deposited in the skeleton. At week 35, calcium deposition increases to 350 mg/d.(16) Building adequate stores of vitamin D for the newborn is important to the maintenance of the structure. Maintenance of vitamin D levels postnatally is also important, especially to those born premature, to avoid skeletal abnormalities. Vitamin D levels impacts fetal shape and limb length.(17) Fetal vitamin D insufficiency is linked to the increased risk of hypocalcemia, type 1 diabetes, asthma and schizophrenia.(18) New studies show that vitamin D status also helps to regulate placental development. This indicates that vitamin D deficiency may contribute to complications in pregnancy such as miscarriage, preeclampsia, and preterm birth.(18, 19)

REFERENCES 1. 2. 3. 4. 5. 6.

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

Along with vitamin B12, folic acid plays a role in nucleic acid synthesis and carbon metabolism. Low maternal folate levels are correlated with smaller newborn weight, and contribute to congenital malformations such as neural tube defects (NTD). Since the fortification of folate in foods, NTD has decreased by 50–70%.(10) More recent studies suggest B12 supplementation can further decrease the risk of NTD.(10) Recently, it has been suggested that folic acid-containing multivitamins may also be beneficial in preventing congenital anomalies other than NTD such as a decreased risk for orofacial clefts, limb deficiencies, and cardiovascular abnormalities.(11)

11.

Increased levels of both folate and B12 help to lower levels of homocysteine, which may contribute to NTD and early pregnancy loss.(12) Low levels of B12 and folate

For more information visit: www.nfh.ca

IHP 2013-12,2014-01 (Pre Natal SAP).indd 2

8. 9. 10.

12. 13. 14. 15. 16. 17. 18. 19.

Pizarro, F., et al. “Iron bis-glycine chelate competes for the nonheme-iron absorption pathway”. The American Journal of Clinical Nutrition 76, No. 3 (2002): 577–581. Jeppsen, R.B. and J.F. Borzelleca. “Safety evaluation of ferrous bisglycinate chelate”. Food and Chemical Toxicology 37, No. 7 (1999): 723–731. Hertrampf, E. and M. Olivares. “Iron amino acid chelates”. International Journal for Vitamin and Nutrition Research 74, No. 6 (2004): 435–443. Pineda, O. and H.D. Ashmead. “Effectiveness of treatment of iron-deficiency anemia in infants and young children with ferrous bis-glycinate chelate”. Nutrition 17, No. 5 (2001): 381–384. Pineda, O., et al. “Effectiveness of iron amino acid chelate on the treatment of iron deficiency anemia in adolescents”. Journal Of Applied Nutrition 46, Issue 5 (2001): 2–13. Goyal, P., et al. “Role of magnesium sulphate for brachial plexus analgesia”. The Internet Journal of Anesthesiology 21, No. 1 (2009): 0–6. Park, O.J. and Y.J. Surh. “Chemopreventive potential of epigallocatechin gallate and genistein: evidence from epidemiological and laboratory studies”. Toxicology Letters 150, No. 1 (2004): 43–56. Kontic-Vucinic, O., M. Terzic, and N. Radunovic. “The role of antioxidant vitamins in hypertensive disorders of pregnancy.” Journal of Perinatal Medicine 36, No. 4 (2008): 282–290. Sharma, J.B., et al. “Oxidative stress markers and antioxidant levels in normal pregnancy and preeclampsia”. International Journal of Gynaecology and Obstetrics 94, Issue 1 (2006): 23–27. Molloy, A.M., et al. “Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic acid fortification”. Pediatrics 123, No. 3 (2009): 917–923. Goh, Y.I., et al. “Prenatal multivitamin supplementation and rates of pediatric cancers: A meta-analysis”. Clinical Pharmacology and Therapeutics 81, No. 5 (2007): 685–691. Ronnenberg, A.G., et al. “Preconception B-vitamin and homocysteine status, conception, and early pregnancy loss”. American Journal of Epidemiology 166, No. 3 (2007): 304–312. Yajnik, C.S., et al. “Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study”. Diabetologia 5, No. 1 (2008): 29–38. Green, R. “Is it time for vitamin B12 fortification? What are the questions?” The American Journal of Clinical Nutrition 89, No. 2 (2009): 712S–716S. Chavarro, J.E., et al. “Use of multivitamins, intake of B vitamins and risk of ovulatory infertility”. Fertility and Sterility 89, No. 3 (2008): 668–676. Holick, M.F. “Resurrection of vitamin D deficiency and rickets”. The Journal of Clinical Investigation 116, No. 8 (2006): 2062–2072. McGrath, J.J., et al. ‘Seasonal fluctuations in birth weight and neonatal limb length; does prenatal vitamin D influence neonatal size and shape?”. Early Human Development 81, Issue 7 (2005): 609–618. Bodnar, L.M., et al. “High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates”. The Journal of Nutrition 137, No. 2 (2007): 447–452. Bodnar, L.M., et al. “Maternal vitamin D deficiency increases the risk of preeclampsia”. The Journal of Clinical Endocrinology & Metabolism 92, No. 9 (2007): 3517–3522.

2013-10-31 11:56:17

Pre Natal SAP

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

ACTIVE INGREDIENTS

Each NON-GMO vegetable capsule contains: Vitamin C (from calcium ascorbate) . . . . . . . . . . . . . . . . . . . . . . . . . 58.33 mg Vitamin D (cholecalciferol) [333.33 IU] . . . . . . . . . . . . . . . . . . . . . . . 8.33 mcg Vitamin E (d-alpha-tocopheryl acetate) [16.667 IU]. . . . . . . . . 11.15 mg AT Vitamin K (vitamin K1) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33.333 mcg Vitamin B1 (thiamine hydrochloride) . . . . . . . . . . . . . . . . . . . . . . . 33.333 mg Vitamin B2 (riboflavin-5’-phosphate sodium) . . . . . . . . . . . . . . . . 16.66 mg Niacinamide (vitamin B3). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16.66 mg Vitamin B6 (pyridoxal-5’-phosphate). . . . . . . . . . . . . . . . . . . . . . . . . 16.66 mg Vitamin B12 (methylcobalamin). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333 mcg l-Methylfolate (from calcium l-5-methyltetrahydrofolate) . . . 333 mcg Biotin (biocytin) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 mcg Vitamin B5 (calcium d-pantothenate). . . . . . . . . . . . . . . . . . . . . . . 33.333 mg Calcium (from calcium citrate) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58.33 mg Iron (from iron glycinate). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 mg Iodine (from potassium iodide). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 mcg Magnesium (from magnesium citrate) . . . . . . . . . . . . . . . . . . . . . . . . . 25 mg Zinc (from zinc citrate) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.33 mg Selenium (from l-selenomethionine) . . . . . . . . . . . . . . . . . . . . . . . 16.66 mcg Copper (from copper citrate) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 666 mcg Manganese (from manganese citrate). . . . . . . . . . . . . . . . . . . . . . . . 1.66 mg Chromium (from chromium polynicotinate) . . . . . . . . . . . . . . . 33.33 mcg Molybdenum (from molybdenum citrate) . . . . . . . . . . . . . . . . . . 16.66 mcg Potassium (from potassium citrate) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 mg Boron (from boron citrate) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233.33 mcg

Contains no: Preservatives, artificial flavor or color, sugar, dairy, starch, wheat, gluten, yeast, soy, citrus or egg. Pre Natal SAP contains 180 capsules per bottle.

DOSAGE

Adults: Take 3 capsules daily with meals or as directed by your health care practitioner.

INDICATION

Pre Natal SAP provides nutritive support for women who are pregnant or who are planning to become pregnant. Non-inclusion of the nutrients beta-carotene and vitamin A: high doses of vitamin A have been shown to cause birth defects when taken during pregnancy. Our formula provides health care practitioners with the flexibility to supplement these micronutrients separately, as needed.

INCREASED BIOAVAILABILITY

ɶ Pre Natal SAP is not compressed with binders for superior assimilation. ɶ Pre Natal SAP is supplied in a vegetable capsule for easy digestion.

PURITY, CLEANLINESS AND STABILITY

Third-party testing is performed on finished product to ensure Pre Natal SAP is free of heavy metals, pesticides and other impurities.

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

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

IHP 2013-12,2014-01 (Pre Natal SAP).indd 1

2013-10-31 11:56:17

Pure joy. It’s Mega joy. Clinically proven to help improve your mental outlook, benefit your heart and support your overall health, genuine Health’s omega3+ joy is formulated with a higher concentration of EPA, making it the best quality Omega-3 you can buy. Certified by our proprietary Superior Quality 5 Point Program, genuine Health’s omega+3 line of Omega-3 fish oils are 3rd party tested to be pure, wild and free of all toxins and PCBs. We start with the purest fish, sourced from fisheries ranked #1 in the world for sustainability. Our fresh technology tm supports optimal absorption with no fishy odour or aftertaste, while our oMegacheck+tm quality program includes over 200 checkpoints to ensure the freshest, cleanest products – from catch to consumer.

guaranteed. For more information about our Superior Quality 5 Point Program, visit us at genuinehealth.com. new Look, same great Formula