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CAND Posters 2011


The Canadian College of Naturopathic Medicine's research posters from the recent Canadian Association of Naturopathic Doctor's conference on June 25-26 in Calgary. _off_

The Canadian College of Naturopathic Medicine's research posters from the recent Canadian Association of Naturopathic Doctor's conference on June 25-26 in Calgary. _off_

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  • 1. A cross-sectional study of patients of the Robert Schad Naturopathic Clinic using the Naturopathic Patient Database Christopher Habib ND (1); Stefan Podgrabinski (2), Matthew Gowan ND (1,2), Brenda Leung ND, PhD (3), Dugald Seely ND, MSc (1,4), Kieran Cooley ND, MSc (1) 1. Canadian College of Naturopathic Medicine 2. OM Corporation 3. Boucher Institute of Naturopathic Medicine 4. Ottawa Integrative Cancer Centre Integrative Background Results Table 1. Conditions Seen at RSNC 2009-2010. ICD-10 % of All % of PatientsThe Naturopathic Patient Database (NPD) is a data management tool developed Females (76%) and people in the 20-30 (31.8%) and 31-40 (18.4%) year old age Conditions Code Range Diagnoses Diagnosedby the Canadian College of Naturopathic Medicine (CCNM) to collect patient groups have the highest representation in the NPD. The pediatric population is Pregnancy-related O00-O99 0.2 0.6data from its teaching clinic, the Robert Schad Naturopathic Clinic (RSNC). This disproportionately underrepresented. Psychosocial problems, musculoskeletal Accidents, poisoning, violence S00-T98 3.0 8.2database was created in 2006 and has evolved to meet the various academic disorders, symptom-based conditions (e.g. fatigue and abnormal laboratory results), endocrine disorders, and gastrointestinal disorders were the most prevalent ICD Cardiovascular disease I00-I99 4.0 11.8and research needs of CCNM. This study describes demographics of patientsand conditions treated by student interns at the RSNC from 2009-2010. groups seen during this period. Health maintenance Z00-Z99 4.1 12.1 Infectious disease A00-B99 4.2 9.5Funding support for the development and use of the NPD was provided by a Figure 2. Conditions Seen at RSNC 2009-2010. Respiratory disorders J00-J99 4.4 12.2grant from the Lotte and John Hecht Foundation. Cancer, neoplasms, hematologic C00-D89 4.8 13.4 Pregnancy-related Methodology Accidents, poisoning, violence Nervous system, sensory organs G00-G99 5.4 14.4 Skin disorders L00-L99 7.1 20.9Fourth year naturopathic interns input data into the NPD as part of an academic Cardiovascualr disease Genitourinary disorders N00-N99 7.8 21.1requirement. Patients can only be entered into the NPD after a minimum of 3 Health maintenance Gastrointestinal disorders K00-K93 9.1 23.3visits. The majority of patients and patient visits are included in the NPD, but not Endocrine disorders E00-E90 10.6 26.8all. Thus, the NPD provides a snapshot of the data captured by interns on Infectious diseasepatients and health care services provided at the RSNC. Other medical R00-R99 10.9 28.3 Respiratory disorders Musculoskeletal disorders M00-M99 11.7 26.9All data from patient files must be entered, beginning with age and gender. The Cancer, neoplasms, hematologic Psychosocial problems F00-F99 12.6 30.0NPD is divided into sections similar to a chart: Subjective, Objective, Nervous system/sensory organsAssessment, and Plan. The NPD also contains a section for outcomes, which Figures 3. RSNC Ages. Figures 4. RSNC Genders. Skin disordersincludes data from the Measure Yourself Medical Outcome Profile (MYMOP). The Genitourinary disorders 0 to 10MYMOP is used as a universal outcome measure of effectiveness ofindividualized patient-defined symptoms. 11 to 19 Gastrointestinal disorders M 20 to 30Figure 1. Screenshot of NPD. Endocrine disorders 31 to 40 Other medical Musculoskeletal disorders 41 to 50 F 51 to 60 Psychosocial problems 61 to 100 Discussion The majority of patients seen at the RSNC are female, likely because females tend This is one of the first Canadian studies using an effective to seek complementary and alternative medicine more than males. The pediatric database tool to obtain a clinical profile of patients seen by population is possibly underrepresented in the NPD because those cases may be naturopathic doctors. Future work is needed to evaluate the more complicated and interns may choose not to select those cases for their delivery of care and utility of the NPD as an effective teaching aid academic requirements or because those patients only come to the clinic for acute and research tool. care. Selected References Acknowledgements Although a wide spectrum of diseases are treated at the RSNC, chronic diseases 1) International Classification This project could not have taken place withoutThe NPD was used to explore RSNC patient cases from 2009-2010. The (diabetes, mental health conditions), diseases with low perceived risk to benefit of Diseases, 10th revision. important contribution from RSNC interns and clinic supervisors from 2006-2010.assessment section of the NPD contains a column for diagnosis that uses the profiles with conventional treatment (chronic pain), and diseases that have a large, 2) Gowan et al. The NaturopathicInternational Classification of Diseases, 10th revision (ICD-10) coding system. modifiable lifestyle component to them (cardiovascular disease), are seen with high Patient Database: a Clinical Tool frequency. More research is needed to understand patient choices to receive care for Research and Education.ICD-10 codes were extracted and reviewed by an expert (CH) for accuracybefore being tabulated. from this institution and to evaluate the effectiveness of care for these disorders.
  • 2. Treating Type 2 Diabetes: A cross-sectional audit of Naturopathic care within a naturopathic college teaching clinic using the Naturopathic Patient Database Christopher Habib ND (1); Stefan Podgrabinski (2), Matthew Gowan ND (1,2), Brenda Leung ND, PhD (3), Dugald Seely ND, MSc (1,4), Kieran Cooley ND, MSc (1) 1. Canadian College of Naturopathic Medicine 2. OM Corporation 3. Boucher Institute of Naturopathic Medicine 4. Ottawa Integrative Cancer Centre Integrative Background ResultsType 2 Diabetes Mellitus (T2DM) is a multi-factorial disease characterized by a The mean patient age was 60 and the female gender was more common (62%). Care Figure 3. Percentage Use of Therapies.decreased response to insulin. The Naturopathic Patient Database (NPD) is a data being provided was predominantly adjunctive care rather than primary care. Themanagement tool developed by the Canadian College of Naturopathic Medicine (CCNM) mean core audit score was 55.5 out of possible total of 90. There was no cut-off 100.0to collect patient data from its teaching clinic, the Robert Schad Naturopathic Clinic score used to determine what was considered adequate care.(RSNC). This study investigates how T2DM is managed at the RSNC from May 2009 to 75.0 PercentageFebruary 2011 for the purposes of auditing clinical supervisors and ultimately Figure 2. Audit Scores for Major Categories.improving patient care. 50.0 2.5Funding support for the use of the NPD was provided by a grant from the Lotte and 25.0John Hecht Foundation and the Diabetes Alternative Research and Healthcare 2Foundation. 0.0 1.5 Methodology Om g m e 10 M A on y ts Ch a-3 ium na a ls th in l lin m AL siu TC en ica m 1 Q- ic eg pa ne m se lem m ed ne Co an eo ro m un M ag Ph Bot Gy pp m Co Ci al M HoA core audit form was created using the American Diabetes Association 2010 Su 0.5 ic ysstandards of medical care. Multiple categories in diagnosis, physical exam, lab tests, 0and management were graded on a 0-2 scale. Criteria being assessed included: KE Tinquiring about current medications, obtaining a detailed history of complications, G S AL BS Figure 4. Relationship of Audit Score vs. NPD Visits Missing. EN IN L TA C RA LA TT EM SImeasuring blood pressure, palpating thyroid, doing a foot exam, obtaining lab results IN FE SE Y AG PH REfor HbA1c and lipid profiles, providing referrals to medical doctors, setting appropriate AL 90 AN GO Mtreatment goals, and utilizing evidence-based prescriptions. 80 Audit Score (Out of 90) Figure 3. 70Additional audit criteria were created that did not apply to all cases, since some 60guidelines only apply to specific patient populations, (eg. referring for bariatric surgery The therapy most commonly used was nutritional supplementation (93%) followed 50if Body Mass Index is over 35). Audit criteria that focused on naturopathic interventions by botanical medicine (69%). Other naturopathic modalities were rarely used to treat 40and RSNC operations were also assessed. These included the recommendations for T2DM or its complications. Of the supplements, omega-3 fatty acids (mean dose: 30various supplements, botanicals, physical medicine, homeopathy, Traditional Chinese 1818 mg daily) was the most common, followed by chromium (mean dose: 681 20Medicine, therapeutic counseling and use of the Measure Yourself Medical Outcome mcg daily). 10Profile (MYMOP) as a universal outcome measure of effectiveness of individualized Interns enter information into the NPD after a minimum of 3 patient visits. An 0patient-defined symptoms. analysis was done to see how audit scores compared to the number of visits that 0 2 4 6 8 10 12 14 were omitted in the NPD. There were no differences among the audit scores,One auditor (CH) conducted a search of the NPD from May 2009 to February 2011 to NPD Visits Missing indicating that the quality of care was largely determined within the first 3 visits.identify patients assessed with T2DM. The assessment section of the NPD contains acolumn for diagnosis that uses the International Classification of Diseases, 10th revision(ICD-10) coding system. The inclusion criteria were all patients assessed with T2DM, so Discussionthat the audit could also capture a realistic representation of naturopathic care for The audit scores evaluating the patient intake were high. This is likely because Feedback is key in improving audit scores and patient care. Audit findingsthose with comorbidities, as is often the case in patients with T2DM. The code for interns spend one hour per visit with patients and so have large amounts of time to were presented to clinical supervisors and to current clinic interns. They wereT2DM (E11) was employed and captured 29 patient cases. accumulate information. The audit scores for lab tests were also high and this is also integrated into the curriculum. The poorest scoring categories were likely because naturopathic doctors in Ontario cannot directly requisition lab tests, so emphasized. A checklist was created to help guide interns in their first 3 visits Figure 1. Process of Case Selection for Audit. credit was given in the audit if an intern requested lab work from the patient. with a diabetic patient. Education and creation of a naturopathic standard of care may improve audit performance and patient outcomes for patients with The three lowest scoring categories in the audit were: a thorough physical exam, 13,824 39 T2DM 37 T2DM 29 T2DM T2DM. Larger scale follow-up audits are planned to examine the impact of Cases (May Cases With referring patient care, and setting specific treatment goals. The physical exam Total NPD Cases With audit feedback and continue the process of practice improvement. Cases (2006 2009 to Feb Complete Patient File component scored poorly because there are guidelines for T2DM that fall outside of to 2011) 2011) NPD Data Identifiers the RSNC’s screening physical exam form. Referring patient care scored poorly, in Selected References Acknowledgements part, because according to the American Diabetes Association, patients must be 1) American Diabetes Association Standards 1) Robert Schad Naturopathic Clinic 13,785 Excluded 2 Excluded 8 Excluded referred to many health care practitioners who’s capabilities often overlap with those of Medical Care in Diabetes 2010. 2) OM Corporation of NDs. Setting specific treatment goals likely scored poorly because there are no 2) Bradley R, Kozura E, Buckle H, et al. 3) Lotte and John Hecht Foundation current guidelines for naturopathic standards of care for diabetes. Collection and Description of Clinical Risk Factor Changes During Naturopathic Care for Type 2 Diabetes. 4) Diabetes Alternative Research and reporting of subjective outcomes (MYMOP) could be improved. Healthcare Foundation
  • 3. Evidence for the Topical Application of Castor Oil: A Systematic Review Deborah A. Kennedy ND1 and Dana Keaton ND LAC2 1Canadian College of Naturopathic Medicine 2Center for Natural Medicine Results Seventeen participants with “fatigue” were recruited to Background participate in an investigation of longer use of COPs.Castor oil, also known as Palma Christi, is derived from the Search Strategy Flow Chart Constipation Participants applied the COPs for 1.5 hours per day over thebean of the plant Ricinus communis, through cold mechanical 462 articles found Researchers Arslen and liver area for 5 days per week for 2 weeks. During the course ofpressing. Ricinus communis is native to India and during initial search Eser evaluated the treatment, the mean total lymphocyte counts normalized within (July 2009)approximately 90% of the oil is produced in Brazil and India. 400 articles rejected effectiveness of COPs on the group and were lower at the end of treatment vs baseline.Castor oil is composed chiefly of ricinoleic acid, which based on title review constipation in 35 elderly As an unexpected outcome, 2 participants with elevated liver 62 abstracts screenedrepresents approximately 80 - 90% of the total fatty acid for inclusion nursing home residents. enzymes and cholesterol levels normalized these variables bycontent. Castor oil has been used since the 16th century BC Constipation symptoms the end of the many forms. It can be taken internally, used topically and 10 articles retrieved for were tracked for 14 daysincorporated into cosmetics and drug delivery systems. It is full analysis using the Defecation Pain Reductionthe evidence associated with the topical application of castor Search re-executed (May 2011) 2 articles Monitoring form and Viera et al compared the anti-inflammatory and antinociceptiveoil that is the focus of this review. 9 articles included in Visual Analog Scale, with effects of topical castor oil and capsaicin. Their findings systematic review COPs applied on Days 8, suggest that castor oil is devoid of irritant properties, unlike 9 capsaicin. Ricinoleic acid was found to deplete substance P. Methodology Capsaicin is used to treat neuropathic pain and the authors and 10. Findings included improvements in evacuation, fecal suggest that castor oil maybe as effective as capsaicin, withoutPubMed, Embase, Alt-Med and CINAHL databases were consistency and a reduction in straining. There were no its irritating properties.searched using the terms castor oil/therapeutic use, changes to the frequency of bowel movements nor thericinoleic acid and Ricinus communis/therapeutic use, not amount of feces evacuated. Discussionricin, from inception to July 2009 and updated May 2011. For Artifical Tears Both castor oil and its main constituent, ricinoleic acid, haveinclusion in the review, articles had to be related to the A double-blind placebo-controlled crossover study by Goto et been found to be non-toxic for both internal and external use.topical use of castor oil. Articles dealing with castor oil used al evaluated low-dose castor oil eyedrops, or artificial tears in Case reports in the literature document evidence of contactin manufacturing, as a food additive, or as a cathartic were 20 patients with obstructive meibomian gland dysfunction. dermatitis from castor oil in cosmetic products.excluded, as was the use of castor oil to aid in the delivery of Treatment with castor oil demonstrated improvement in Historically, castor oil has been reputed to provide relief forpharmaceutical drugs. symptoms and objective findings. Maissa et al also found that dermatologic conditions, contusions, inflammatory and ocular eyedrops containing castor oil produced a more stable tear disorders. This review disclosed no cohesive evidence regarding Results film and a significant decrease in ocular dry eye symptoms. the mechanism of action of castor oil or its main constituent,Nine studies investigated the topical use of castor oil ricinoleic acid. Immune and Liver functionthrough direct application of the oil or in the form of castor Preliminary evidence suggests that castor oil may modulate A double-blind controlled study of a single use of COPs vsoil packs (COPs). white blood cell count and may have a positive effect on liver paraffin oil packs in 36 healthy adults found an increase inTransdermal Absorption function and cholesterol levels; further research is needed in this total lymphocytes which peaked at 7 hours with T11 cellsMein et al conducted a small study to assess castor oil area. The topical application of castor oil has been shown to contributing to the overall increase. COPs were applied overabsorption through the skin vs oral intake. A 2-phase study reduce the pain of neurogenic inflammation, improve symptoms the liver and abdomen for 2 hours with heat. At the 24-hourcomparing abdominal COPs for 3 consecutive days versus of constipation and to lubricate the eyes as artificial tears. mark, total lymphocytes declined, although they remainedoral consumption found no significant difference in the within normal limits.urinary metabolites of castor oil pre- and post-COP while Acknowledgements.significant differences were found pre- and post-oral intake. Deborah Kennedy’s efforts on this project were supported by a career development grant from the SickKids Foundation.
  • 4. Xenoestrogens & Breast Cancer: Chemical Risk, Exposure and Social Determinants Sarah Young, MA (1) & Dugald Seely, ND, MSc, FABNO (1,2,3) 1. Ottawa Integrative Cancer Centre 2. Department of Research & Clinical Epidemiology, Canadian College of Naturopathic Medicine, Toronto 3. Ottawa Hospital Research Institute Medicine, Background Xenoestrogens and Breast CancerIncidence of breast cancer has risen in Canada by more than 25% Table 1: Common Xenoestrogens, sources and effectsover the past twenty-five years, is the leading cause of death in Xenoestrogens are chemicals thatwomen aged 20-44, and comprises over thirty percent of all cancer mimic the effects of estrogen due to XENOESTROGENS FOUND IN EFFECTSdiagnoses in women. Nearly two-thirds of breast cancer cases result structural chemical similarities. Asfrom a combination of gene-environment interactions, lifestyle opposed to endogenous hormones, Bisphenol A (BPA) bottles, tin cans, drink containers, In vitro and animal studies: water pipes, dental composites, optical neoplastic development,factors (including lack of physical exercise, alcohol intake, and xenoestrogens come from sources lenses, adhesives, compact discs, paper proliferation of epithelial cells, coatings expression of estrogen receptorsobesity), and exposure to environmental pollutants. Exposure to external to the body. Like other (ERs) and progesterone receptors (PRs), and a decreased vaginalestrogen is the most important identifiable risk factor responsible endocrine disruptors, xenoestrogens weight, transgenerationalfor the development of breast cancer. While endogenous estrogen is can alter normal hormonal function, amplification.clearly important, the contribution that xenoestrogens have on producing adverse health effects for Polychlorinated electrical equipment, plasticizers in Human studies: high levels foundbreast cancer causation is just starting to be documented. both adults and their children. Biphenols (PCB’s) paints, plastics, and rubber products, pigments, dyes, and paper. Though in breast milk of northern communities banned in 1979 PCBs are still released PCBs are now regularly found in Mammary tissue cells express specific into the environment from hazardous waste sites. PCBs do not readily break mammals and ocean wildlife in the far north Chemicals in Our Environment receptors, known as alpha-receptors down and remain for long periods of time recycling between the air, water, that can be stimulated by estrogens to and soil.There are over 80,000 synthetic chemicals in and around us: they are induce the proliferation of end buds in Certain Pesticides used extensively in agriculture, in In vitro and animal studies:sprayed directly on our food in the form of pesticides; they get the breasts. Proliferation of these end (i.e. DDT, heptachlor, atrazine, chlordane, homes, in workplaces, and throughout cities on private and public lawns immunotoxic, mutagenic, carcinogenic, enhances thepumped into the air by diesel exhaust and industrial emissions in the buds increases the risk of breast aldrin, lindane, 2,4,5-TP and the captans) metabolism of other xenobiotic chemicalsform of polycyclic aromatic hydrocarbons (PAHs); they are used as cancer by augmenting the chance of Occupational studies: women working in agriculture 3 timesliners in tin cans, are built into plastic water bottles and are found in mutation during cell division. more likely to have breast cancerdental composites in the form of bisphenol A (BPA); are added to There are over 200 xenoestrogens used in industry, cosmetics, Cadmium from burning fossil fuels and In vitro and animal studies:personal care products in the form of parabens; leach into the soil agriculture and food processing that act as mammary carcinogens municipal waste, the smelting of zinc and copper, and tobacco smoke. induction of single-strand DNA breaks, inhibition of DNA repairand water from electronic waste in landfills in the form of cadmium, Cadmium is used in electroplating, in by inactivation of the mismatch and have been found in over 95% of human tissue. Twenty-nine of alloys, as a de-oxidizer in nickel repair system, activation ofand are found in high amounts in the fish we eat as polycyclic plating, in Cd-Ni batteries, as oncogenes, inhibition of these compounds are produced at over a million pounds per year pigments in glazes and enamel paints, programmed cell deathbiphenols (PCBs). in plastics, and in fertilizers. Parts of (apoptosis). in the USA. North America are known to have high levels of cadmium in the soil. Occupational studies: Women working in automotive were 4Since the 1950’s more than 750 million tons of toxic chemical waste times more likely to have breast cancer.have been discarded across 50,000 hazardous waste sites in the Relevant Social DeterminantsUnited States alone. Among all North American jurisdictions, Ontario Parabens, Pthalates Personal care products, including Breast cancer rates amongst Exploring the impact of xenoestrogens from a social determinants shampoos, creams, conditioners, African American women underis the fourth highest emitter of cancer causing chemicals into the air, hairsprays, deodorants, cosmetics, and age 30 are 50% higher than white of health model, we found that early life, food security, social perfumes women and their use of estrogenicemitting over four million kilograms of reproductive toxins each year. personal care products is ten exclusion, education, working conditions, income, housing, and times higherXenoestrogens consist of a class of endocrine disrupting chemicals availability of a social safety net had a significant impact on the Polycyclic Aromatic fossil fuel combustion, diesel exhaust, In vivo, in vitro and human(EDCs) that have causative links to cancer and particularly to breast risk of exposure. These issues speak directly to breast cancer Hydrocarbons (PAH’s) consumption of smoked and grilled foods, and from cigarette smoking studies: mutagenic, increased proliferation of cells, effects oncancer. Common xenoestrogens include Bisphenol A, PCB’s, risk and chemical exposure and inequities in society as well as the estrogen receptors, enzymes of the CYP 450 family and on theCadmium, Pesticides, PAHs, Parabens and Pthalates (see table on issue of vulnerability. The timing of exposure to increased levels of tumour suppressing generight for more detail and examples). both natural and chemical xenoestrogens in a woman’s body, embryo, fetus, and infant plays a key role in the development of Acknowledgements. This review was funded by the National cancer. Network on the Environment and Women’s Health
  • 5. An observational study of adjunctive cancer care at the Canadian College of Naturopathic Medicine Gillian Flower ND1, Natalie Bozinovski ND(c)1, Gabriella Chow ND1, Kieran Cooley ND1, Martha Grant ND1, Christopher Habib ND1, Daniel Lander ND, FABNO1, Tara O’Brien ND1, Jill Shainhouse ND, FABNO1, Dugald Seely ND, FABNO1,2. O’ 1. Canadian College of Naturopathic Medicine; 2. Ottawa Hospital Research Institute Table 1. Select patient characteristics by cancer type Diet, lifestyle and mind-body interventions were common, as Background was individualized homeopathy, tinctures and teas. Mean age at % reportingThe Adjunctive Cancer Care (ACC) shift provides Primary cancer Female / Number of Analysis of EORTC, MYCAW, MYMOP and KI showed that diagnosis – years conventionalnaturopathic care to patients with cancer at the Robert type male patients scores improved or were unchanged more frequently than (range) care pre-RSNCSchad Naturopathic Clinic (RSNC), the teaching clinic of the Breast 31 / 0 31 49 (30-76) 80.6 they worsened (Figure 1). This was true across all scores andCanadian College of Naturopathic Medicine (CCNM). This Digestive1 17 / 10 27 55 (2-83) 88.9 subscores in all measures used. The subset of eligiblecross-sectional, observational study summarizes Prostate 0 / 20 20 61 (48-79) 40.0 responses per tool was small (n= 11-30) although 39.1% ofdemographic, outcome and treatment data for patients all charts yielded eligible responses for at least 1tool. Hematologic 8/6 14 45 (23-63) 78.6seen on the ACC over a 13-month period. Female reproductive2 13 / 0 13 52 (26-71) 100.0 The 5 most common patient-identified concerns, elicited Neurologic 4/5 9 21 (0-67) 88.9 through MYCAW use included: references to cancer, to pain Methodology Head and neck3 5/2 7 53 (32-74) 85.7 or discomfort, to energy or fatigue, to weight or Other4 9/8 17 54 (33-83) 47.1 nutrition or to gastrointestinal symptoms. 84.2% ofPoint-of-sale software was used to identify patients that had evaluated patients named at least one of these 5 concerns.been seen on the ACC from December 2009-December 1 – Colorectal, hepatic, pancreatic, gastric; 2 – ovarian, uterine, vaginal; 3 – salivary, oral, thyroid, sinus; 4 – includes lung, skin, testicular, osseous, diverse types not included elsewhere2010. The in-house Naturopathic Patient Database (NPD)was consulted for patient information, but a lack of 18% of patients reported a refusal of conventional treatment at some point, Discussionsufficient data led to a full patient chart review. many having tried chemotherapy or radiation previously. 9 deaths (6.5%) A diverse range of patients and cancers (type and stage) arePatients were included if they had a diagnosis of cancer and were confirmed. seen by student interns on the ACC at the RSNC. Treatmentshad >1 visit on the ACC. 35 data points were collected in include supplemental, lifestyle and dietary therapies and reflect 51% of all patients received intravenous vitamin C therapy (IVC), with use a blend of cancer-focused and individualized care.addition to scores on 4 validated assessment tools: the ranging from 45%-71% across various cancer types. Far fewer patientsKarnofsky Index (KI), the Measure Yourself Medical with neurologic cancers received IVC (11%), but only 4 patients in this Patient-defined symptoms commonly include concerns with painOutcomes Profile (MYMOP), the Measure Yourself Concerns group were eligible to receive this treatment in Ontario (>13 years old). and energy. EORTC results show fewer patients worsening inand Wellbeing scale (MYCAW) and the European these subscores than the number that maintain their currentOrganization for Research and Treatment of Cancer quality Oral supplementation was recommended in 98.5% of patients that had at status or improve. Other patient- and intern-based assessmentsof life questionnaire (EORTC). Intern prescriptions were also least 1 consult-type visit. All supplemented patients were given at least one of symptoms and function include the MYCAW, MYMOP and KI.counted. of the following 5 prescriptions: Vitamin D, curcumin, EGCG, All suggest a trend towards patient stabilization or improvement melatonin and fish oil. in evaluated outcomes. Results Figure 1. Percent of patients improving, not changing and worsening according to EORTC(1-5), MYCAW (6-7) and Karnofsky (8) results (>27 days of evaluation). Some limitations to this study include the small amount of eligible data for each tool. Responses were included if the same189 patient charts were reviewed and 138 met criteria for tool was used on more than 1 occasion and if the time elapsedinclusion. 64% of patients seen were female. Breast cancer 100% between administration was >27 days yielding as few as 11was the most common diagnosis, seen in 22.5% of all 80% responses in one instance. The original goal of using the NPD ascases. Mean age at diagnosis was lowest among neurologic Worsened a source of data could not be met, necessitating a chart review.cancers where 5/9 patients were 3 years of age or 60% Unchangedyounger. Short- and long-term naturopathic care may successfully 40% Improved address some of the most important concerns of individualsTable 1 summarizes select patient characteristics. with cancer. Further research investigating patient experiences 20% and comparative effectiveness of naturopathic treatment ofAverage duration of care was 298.4 days (range 2-2163), 0% cancer are warranted.with an average of 7.4 (0-70) consult-type visits per patient.51.5% of all patients had conventional treatment (surgery, l  ky  1 ue ain g e lth na ein Acknowledgements: tiv rn fs igchemotherapy, radiation or other) during the course of their ea  P io no ni ce at lb 4. ot l H Our thanks to the interns of the ACC shift 2009- og on el  F arcare at the RSNC.  Em ba  W 3.  C  K 2011 and the Lotte & John Hecht Memorial  C 5. 8. lo 6. 7. 1. Foundation.  G 2.
  • 6. Naturopathic Medicine for the Prevention of Cardiovascular Disease: A Pragmatic Randomized Clinical Trial Dugald Seely ND, MSc (1), Orest Szczurko ND, MSc (1), Kieran Cooley ND, MSc(c) (1,2), Heidi Fritz ND, MA (1), Serenity Aberdour ND (1), Craig Herrington ND (1), Patricia Herman ND, PhD (1) MSc(c) Philip Rouchotas MSc, ND (1), David Lescheid ND, PhD (1), Ryan Bradley ND (1), Tara Gignac ND (1), Bob Bernhardt, MEd, LLM, PhD (1), Qi Zhou, MSc (3), Gordon Guyatt MD, MSc, FRCPC (3) MSc, MEd, MSc, 1. Department of Research & Clinical Epidemiology, Canadian College of Naturopathic Medicine, Toronto 2. University of Toronto 3. McMaster University, Hamilton College Background Results Secondary End Points. Significant improvements were seen among a number of secondary outcomes compared to the control group: waist circumferenceRisk of atherosclerotic cardiovascular disease (CVD) is modifiable depending upon management Baseline Characteristics. The groups were comparable at baseline. The treatment group (mean 1.91 cm, p=0.0049), TC: HDL ratio (mean 0.82, p=0.0005), and systolicof risk factors including cholesterol, blood pressure, diabetes, overweight and obesity, activity reported significantly more minutes per week spent in moderate exercise (p=0.01), however, this blood pressure (mean 6.77, p=0.0001). Non-significant trends (p<0.1) towardlevel, smoking, and dietary factors. Metabolic syndrome is a cluster of such risk factors, listed was not associated with a lower incidence of metabolic syndrome, better lipid parameters, or improvement were seen for HDL-C, HbA1C, and diastolic blood Table 1. Standard care for prevention of CVD emphasizes pharmacotherapy with antilipid, lower body weight/ body mass index (BMI). There was also significant improvement in subjective ratings of non-antihypertensive, and hypoglycemic medications. Although the importance of lifestyle cardiovascular related symptoms as assessed by the MYMOP questionnaire: Primary End Points. After one year, incidence of metabolic syndrome and 10-yearinterventions is widely recognized, few patients at risk of CVD receive the intensive dietary and activity, well being, and required medication use to control these symptoms. cardiovascular risk decreased significantly compared to baseline in the treatment group. Theselifestyle counseling necessary for them to make changes. We investigated whether naturopathic These symptoms included musculoskeletal pain, fatigue, sleep concerns, and results became more significant when compared with the control in addition to standard care could reduce risk of CVD in comparison to standard care weight gain. A non-significant trend (p<0.1) toward improvement was also seenalone, over a one year period. The treatment group had a 14% reduction in the incidence of metabolic syndrome, meaning that for physical function on the SF-36 questionnaire. All treatments were well 15 people out of 104 who had metabolic syndrome at the beginning of the study no longer met tolerated; no serious adverse events attributable to the interventions occurred. Methodology diagnostic criteria at one year. When compared to the control group, this difference became 27.4%, RR 0.73 (95% CI 0.58 to 0.87; p = 0.0002). Table 3. Secondary Outcomes With Significant Improvement at 12 monthsWe conducted a pragmatic randomized controlled trial Table 1. Criteria for Metabolic Syndrome Change from Difference of The treatment group had a significant 2.19% reduction in their 10-year cardiovascular risk Baseline Baselinecomparing individualized naturopathic care to standard Measure Categorical Cut Point Outcome 12 months Change Between Mean +/- SD Meancare for the prevention of cardiovascular disease. A total (3 of 5 = (Grundy 2005) compared to baseline according to the Framingham algorithm. When compared to the control Groups diagnosis) (95% CI), p valueof 1125 subjects were prescreened from a pool of group, risk decreased to 3.6% (95% CI -5.1% to -2.3%; p < 0.0001). This means that for every Waist circumference -1.98 (-2.94, -1.02) -1.91 (-3.23, -0.58) Waist ≥102 cm (40 in) men OR 100 people at high relative risk for cardiovascular disease, more than three will not experience a 101.42 +/-13.55 99.44 +/-13.66Canadian Union Postal Workers (CUPW) in Toronto, circumference (cm) -P=0.0001 P=0.0049 ≥88 cm (35 in) womenVancouver, and Edmonton; 246 with the highest relative serious cardiovascular event like a stroke, heart attack, or death during the next ten years. TC:HDL ratio (mmol/L) -0.26 (-0.59, 0.06) -0.81 (-1.26, -0.36) 5.26 +/-1.57 4.99 +/-1.53risk of CVD were randomized, and 207 completed the HDL cholesterol <1.03 mmol/L (40 mg/dL The treatment group had a significant 3.5 year reduction in their mean adjusted vascular age p-=0.1064 P=0.0005 for men ORone-year trial. Subjects in the treatment group received compared to baseline as measured by the Framingham algorithm. When compared to the control Systolic blood -6.79 (-9.09, -4.49) -6.77 (-10.18, -3.37) <1.30 mmol/L (50 mg/dL 125.21 +/-16.4 118.42 +/-12.15seven visits with a naturopathic doctor (ND) over the for women OR medicated group, there was a reduction of 5.4 years in the treatment group (95% CI -7.7 to -3.1). pressure P<0.0001 P=0.0001)course of a year. Primary endpoints were: incidence ofmetabolic syndrome, 10-year risk of having a Triglycerides ≥1.7 mmol/L (150 mg/dL) OR medicated Figure 2. Incidence of metabolic syndrome at 12 months Figure 3. 10-year cardiovascular risk at 12 months Figure 4. Cardiovascular Age at 12 monthscardiovascular event, and heart age, using theFramingham algorithm and the Adult Treatment Panel Blood pressure ≥130 systolic BP OR Incidence of Metabolic Syndrome 10-year Cardiovascular Disease Risk Cardiovascular Age(ATP) III diagnostic criteria for metabolic syndrome. ≥85 diastolic BP OR 100 62 medicated 14Secondary outcomes included quality of life as measured 90 60 80 12by the SF-36 and MYMOP questionnaires. Fasting glucose ≥5.6 mmol/L (100 mg/dL) 70 58 OR medicated 10 1 0 -y ea r % R isk 56 A p p arent ag e P ercen ta g eDuring the visits, each subject received individualized 60 Treatment 8 Treatment 54 Treatment 50naturopathic care, with emphasis on dietary and lifestyle counseling as well as prescription of 40 Control 6 Control 52 Controlselect nutraceutical and botanical prescriptions. An expert panel consisting of four NDs 30 4 Δ = - 3.6%; 95% CI (-5.1%, -2.3%) p<0.0001 50 Δ = - 27.4%; 95% CI (-41.74%, -13.07%) Δ = -5.4; 95% CI -7.7, -3.1) p< 0.0001provided guidance on use of these treatment modalities based on existing evidence and clinical 20 p = 0.0002 2 48 10 46experience. 0 0 44 Table 2. Evidence Based Interventions Baseline Week 52 Baseline Week 52 Baseline Week 52Figure 1. Study Flowchart Intervention Daily Dose Timepoint Timepoint Timepoint Dietary Prescriptions 1125 Portfolio/ DASH/ n/a CUPW members Mediterranean Diet prescreened 879 not enrolled due to lack of interest, ↓saturated, trans fat, cholesterol n/a Discussion low TC/HDL ratio Raw almonds/ walnuts ¼ to ½ cup (14-28) 246 interested participants with AND/OR not meeting Raw extra virgin olive oil 2 tbsp This study provides evidence that metabolic syndrome can be prevented and reversed through One of important merits of this trial is its transferability to a real world setting inclusion/exclusion highest relative risk of CVD consented criteria Fruit and vegetable intake 4 svg each lifestyle changes achieved through intensive dietary and lifestyle counseling and nutraceutical and generalizability of the results. With a pragmatic design whereby treatment is Fibre: oatmeal/ oatbran ½ cup prescriptions provided by naturopathic doctors in addition to standard care. The overall incidence 1) delivered as a comprehensive, whole- system of care, and 2) the components Soy protein 50g Randomization Coffee Avoid of metabolic syndrome was reduced by 27.4% over the course of one year in comparison to thereof are individually tailored to mimic how care is given in the community, Fatty fish consumption 2-3 x/wk standard care alone. When analyzed according the Framingham algorithm, 10-year there is a clear generalizability of this service of care. Supplement Based Prescriptions cardiovascular risk decreased by 3.6%, and heart age decreased by 5.4 years. With ongoing Naturopathic Treatment + Usual Care for 12 months Fish oil 2000 mg EPA+DHA According to the American Heart Association, the “prime emphasis in Usual Care for 12 months N = 122 treatment extending over many years, as is closer to a real world situation, these effects would N = 124 Plant sterols 500 mg tid w meals management of the metabolic syndrome per se is to mitigate the modifiable, be expected to grow proportionately. Cinnamon 1000 mg or ½ tsp underlying risk factors (obesity, physical inactivity, and atherogenic diet) through 18 (14.5%) 21 (17.2%) Coenzyme Q10 100 mg w food Dropped Dropped The results reported above are an underestimate of the true treatment effect since they do not lifestyle changes….Then, if absolute risk is high enough, consideration can be Lutein 10 mg out out Fibre 1 sachet 1-2 x/d account for differences in treatment compliance. Participants with higher adherence to prescribed given to incorporating drug therapy to the regimen” (Grundy 2005). Primary Lifestyle Based Prescriptions treatments would be expected to show much greater improvement compared to those with low healthcare practitioners that provide in depth counseling around diet and lifestyle 106 (84.5%) 101 (82.3%) Weight loss of 5-10 lbs 1-2 lb/wk compliance. In addition, the control group was given handouts with information about diet and are uniquely poised to co-manage these metabolic risk factors. Exercise, aerobic 30 min 5+ times/wk evaluable using evaluable using Exercise anaerobic 2-3 x/wk exercise at baseline that may have benefited this group and offset some of the true difference Acknowledgements. This project was funded by the Joint Benefits Committee of the Canadian ITT ITT between naturopathic treatment and usual care. Union of Postal Workers (CUPW) and the Canada Post Corporation. Diaphragmatic breathing 10 min
  • 7. Fish Derived Omega-3 Fats For Lung Cancer: A Systematic Review Heidi Fritz ND, MA (1), Deborah Kennedy MBA, ND (1,2), Dean Fergusson PhD (3), Rochelle Fernandes MSc, ND(c) (1,2), Kieran Cooley ND MSc(c) (1,2), Fergusson ND(c) MSc(c) Andrew Seely MD, FRCPC (3), Raimond Wong MD, FRCPC (4), Stephen Sagar MD, FRCPC (4), Dugald Seely ND, MSc (1,3) 1. Department of Research & Clinical Epidemiology, Canadian College of Naturopathic Medicine, Toronto 2. University of Toronto 3. Ottawa Hospital Research Institute 4. Juravinsky Cancer Center College Background ResultsFish oils containing omega-3 (ω-3) fatty acids have been shown to Table 1. Controlled Clinical Trials of Fish Derived Omega-3 Fatty Acids in Lung Cancer Patients Figure 2. Lung Cancer Related Preclinical Mechanismspossess strong cardioprotective and anti-inflammatory properties Ref Population Intervention/ Control Outcomes +/- J scoremediated by the ω-3s eicosapentanoic acid (EPA) and docosa- RCTshexanoic acid (DHA). The anti-inflammatory effects of fish oil may 1 n=40 advanced NSCLC pt I: EPA 2g + 0.92g DHA/d in a fortified Significant increase in fat free mass in the EPA group at 3wks and 5wks c/t control group + 5benefit patients with cancer related metabolic syndromes and/ or undergoing cisplatin based drink x 5wk plus chemo/ radiation (difference of 1.5kg, p=0.05; 1.9 kg, 0.03 respectively). Similar increase in total body weight (p=0.02, 0.04). There was a trend to ↑mean upper arm circumference at 5wk (p=0.06). Nocancer induced cachexia, both of which are characterized by high chemo/ radiation C: Isocaloric drink without EPA/ DHA serious adverse events. in addition to chemo/ radiation therapylevels of systemic inflammation . 2a n= 332 advanced cancer pt I: EPA 2.2g/d as protein drink x 16wk Groups receiving EPA alone and progestrogenic agents alone had worsening of endpoints: lean m 3 ,b (72 lung) C: progesterogenic agent; body mass, resting energy expenditure, and fatigue at study interim so treatment was d/c’d.Supported by the Canadian Institutes of Health Research (CIHR), we 5 treatment arms L-carnitine; thalidomide; or all 4 The combination arm including EPA had improvement for all endpoints c/t baseline (p<0.05). Anticancer effect in vivo, n=9conducted a systematic review on the safety and efficacy of fish 3 n=22 NSCLC pt I: Fish oil 6g/d (18% EPA) x 6wk Both groups had ↓CRP, ↓fatigue, and ↑appetite c/t baseline (p<0.02 for all). Fish oil + + 4 Antiproliferative effects/ growth inhibition, n=7derived ω-3 fatty acids in patients with lung cancer. C: Fish oil + celecoxib 400mg/d celecoxib also had significant ↑handgrip strength (p=0.002) and ↑body weight (p=0.05) c/t Anti-metastatic effects, n=7 baseline. No AE. Inhibition of PGE2, n=5 4 n= 518 pt with advanced lung I: EPA 2g or 4g per day x ≥8wk Trend to ↑body weight in the EPA group c/t placebo (p=0.066). n+ 5 Cytotoxicity, n=5 Methodology and GI cancers, who had lost ≥5% baseline weight and not C: Placebo Physical function ↑7% (significant) in the 2g dose group and ↓5% (p=0.04) in the 4g group c/t placebo. However the 4g group started the study with a 10-point lower performance score. Potentiation of chemotherapy, n=5 Proapoptotic effects, n=4 on chemotherapy Trends to ↓weakness in the treated patients.We searched the following electronic databases for evidence 5 n= 421 pt with advanced I: EPA fortified drink: 2.18g EPA The % patients achieving 10% weight gain from baseline was 6% for fish oil, 18% for n+ 3 Anti-cachectic effects, n=2pertaining to fish-derived ω-3 fatty acids and lung cancer: cancer (118 lung) and +0.92g DHA/d megesterol acetate (MA), and 11% for both. MA was significantly better than fish oil (p=0.004). Immune modulation, n=1 cachexiaPubmed, EMBASE, CINAHL, the Cochrane Library, and the National C: Megesterol acetate + Isocaloric Appetite ↑~65% in all groups on NCCTG questionnaire. Addition of fish oil to MA reduced 3 study arms placebo drink OR both incidence of thromboembolic events: 6% in fish oil, 8% in MA, and 2% in the combined group.Library of Science and Technology, from inception until May 2011. Table 2. Summary of Observational Evidence 6 n= 60 advanced cancer pt (11 I: Fish oil 18g/d x 2wk (3.2g EPA + There were no significant differences in appetite, nausea, well-being, caloric intake, or function n 5We used a broad MeSH and keyword based approach combining lung) with anorexia/ cachexia 2.2g DHA/d) c/t placebo. Fish oil patients reported more tiredness on visual analog scale (VAS) (p=0.04). Design Number of Highlights of Findings However, the placebo group had borderline significantly better performance status at baseline Positive/clinical (lung cancer) and therapeutic (fish oil) search terms. C: Placebo (p=0.05), and the study was only 2 weeks. Neutral/ Fish oil ↑survival c/t placebo (p<0.025). Fish oil ↑performance score from 51 to 72 in Negative StudiesAll levels of evidence were included. Initial screening was based on 7 n= 60 advanced cancer pt (20 lung) I: Fish oil 18g/d (3.1 gEPA+ 2.1g DHA) until death malnourished patients when taken for >40d. + 3 Prospec 3/ 1/ 0 Decline in plasma phospholipid EPA wastitle or abstract review. Data extraction was piloted in duplicate C: Placebo Fish oil restored Thelper/ Tsuppressor cell ratio in malnourished patients (p<0.05). tive most marked in those with muscle lossusing forms based on standardized reporting guidelines. Non-randomized Controlled Trials Cohorts ≥3kg over the course of the study, r2=.99. 8 n=46 advanced NSCLC pt I: EPA 2.2g/d plus b/w 240-500mg Response rates (complete or partial response) = EPA group 60% c/t 25.8% (p=0.008). + -- Lung cancer was ↓68% among those who undergoing firstline platinum DHA x >6wk + SOC chemotherapy consumed fish or shellfish 2-3x/wkFigure 1. Literature Flow Chart: based SOC chemotherapy Clinical benefit (objective response or disease stabilization) = 80% c/t 41.9% (p=0.02). compared to <1x/wk, RR 0.32 (95%CI C: SOC chemotherapy Survival at one year = 60% c/t 38.7% (p=0.15). (contemporaneous controls) 0.13-0.76) 1496 records selected for initial screen 9 n=40 advanced NSCLC pt Same as above (8). Change in body weight = EPA group +0.5 kg c/t control -2.3 kg (p<0.05) + -- Case 6/ 2/ 0 Consumption of fish oil was associated undergoing firstline platinum Muscle rate of change (% /100d) = EPA group +0.1 c/t control -6.8 (p<0.05) Control/ with 40% ↓ lung cancer risk, RR 0.60 based SOC chemotherapy Cross- (0.46-0.79). Lower levels of EPA, DHA, or 1408 records excluded after deduplication % who gained or maintained weight = EPA group 69% c/t control 29% (p value not reported) sectional total omega-3 in platelet phosphoglyceride and initial title/ abstract review Key: (+) outcome supporting anticancer activity of fish oil; (-) outcomes show increased risk or harm associated with selenium; (n) no significant effects; (m) both positive and negative outcomes seen; fractions in lung cancer patients. AE adverse events; b/o based on; c/t compared to; d/c’d discontinued; NS non significant; pt patients; QOL quality of life; SOC standard of care; wrt with respect to 88 full text articles screened Discussion 33 records excluded Preclinical evidence most strongly supports in vivo anticancer effects, Clinical Implications Cancer induced cachexia is a proinflammatory condition • 11 reviews antiproliferative, and antimetastatic effects for fish oil in lung cancer. There is characterized by ≥5% weight loss in the last year in addition to three of the following: • 7 not relevant to lung cancer or fish oil also some support for an anti-cachexic effect (2 studies). decreased muscle strength, fatigue, anorexia, low fat free mass index, or abnormal • 15 other or duplicate Human Evidence Of nine clinical studies, six compared fish oil to an inactive chemistry including increased inflammatory markers (10). The potential ability of EPA placebo or control group. Two trials (1,9) found benefit from fish oil on total and DHA to slow or prevent cachexia in patients with lung cancer due to its anti- body weight and lean body mass; and one trial (4) found improvements in inflammatory activity is an important finding since cachexia is a powerful determinant 55 Studies Included for Full Analysis and Review physical function. Fish oil compared to progesterogenic agents failed to show of survival, treatment response, and quality of life in cancer patients (11, 12). • 7 RCTs Therapeutic dose of EPA ranges from 2 to Acknowledgements: Funded by the Canadian Institutes of Health • 2 non-randomized, controlled trials superiority for weight maintenance, however, it should be noted that these 4g per day in divided doses. Although Research (CIHR) • 4 uncontrolled phase II trials agents cause increased weight via water retention and fat mass, while fish oil there has been concerns with fish oil References: 1 van der Meij 2010 7. Gogos 1998 • 12 observational • 30 preclinical impacts lean mass. Two trials found increased survival among patients treated increasing risk of hemorrhage based on 2a. Mantovani 2008 8. Murphy 2011 A 2b. Mantovani 2010 9. Murphy 2011 B with fish oil (7, 8), and three trials showed benefits on weight & lean mass case reports, this was not observed in the 3. Cerchietti 2007 10. Evans 2008 and/ or survival when used alongside chemotherapy (platinum based) (1,8,9). trials included in this review. 4. Fearon 2006 5. Jatoi 2004 11. Vigano 2000 12. Dewys 1980 6. Bruera 2003
  • 8. Green Tea and Lung Cancer: A Systematic Review Heidi Fritz ND, MA (1), Deborah Kennedy MBA, ND (1,2), Dean Fergusson PhD (3), Rochelle Fernandez ND (cand) (1,2), Kieran Cooley ND, MSc(c) (1,2), Fergusson (cand) MSc(c) Andrew Seely MD, FRCPC (3), Raimond Wong MD, FRCPC (4), Stephen Sagar MD, FRCPC (4), Dugald Seely ND, MSc (1) 1. Department of Research & Clinical Epidemiology, Canadian College of Naturopathic Medicine, Toronto 2. University of Toronto 3. Ottawa Hospital Research Institute 4. Juravinsky Cancer Center College Background ResultsGreen tea (Camellia sinensis) and green tea extracts are among the Table 1. Intervention Studies in Humans Figure 2. Catechin Structuresmost commonly used natural health products (NHP) by cancer About Catechins Ref Population Intervention Outcomespatients, due to their widely reported anticancer properties. •A class of flavonoids Phase I Trials - Treatment •Four of the primaryCatechin polyphenols with potent antioxidant capacity are thought 1. n= 17 patients with advanced I: Green tea capsules Maximum Tolerated Dose (MTD) 3.0 g/m2/d. catechins in green tea are:to be responsible for green tea’s anticancer effects. incurable lung cancer (NSCLC (13.9% EGCG, 6.8% Tumor Response (after 4 weeks) •EGCG (epigallocatechin or SCLC) caffeine) in escalating –No objective tumor response gallate)Up to 11.5% of lung cancer patients using complementary and doses –Disease Progression: 7 patients •ECG (epicatechinalternative medicine (CAM) use some form of medicinal tea. Despite –Disease Stabilization: 10 patients gallate) •EGC (epigallocatechin)this, there has been no knowledge synthesis around its potential Dose Limiting Toxicities (DLTs) Grade 3 diarrhea, nausea, and hypertension, ameliorated by dose reduction. No Grade 4 toxicity. •EC (epicatechin)risks and benefits in lung cancer. Supported by the Canadian 2. n= 49 patients with incurable I: Green tea capsules Maximum Tolerated Dose (MTD) 1.0 TID or 4.2 g/m2/donce daily. g/m2 • Potent antioxidants:Institutes of Health Research (CIHR), we conducted a systematic cancer, 21 with NSCLC. (13.2% EGCG, 6.8% Tumor Response •25 x stronger than vitEreview of green tea for lung cancer. caffeine) with dose –“No major tumor response” •100 x stronger than vitC escalation from 0.5 to 5.05 g/m2 per day. –Disease Stabilization: 10 patients (completed 6mo treatment) • Ability to ↓ DNA damage Dose Limiting Toxicities (DLTs) Gastrointestinal upset and CNS stimulation Methodology Surrogate Studies – Prevention (insomnia, agitation), though to be secondary to caffeine content. Table 3. Mechanisms Supported by Preclinical EvidenceWe searched the following electronic databases for evidence 3. n= 133 heavy smokers I: Decaf green tea, 4 – Significant ↓ in creatinine-adjusted 8-OhdG (urinary marker of DNA damage) frompertaining to selenium and lung cancer: Pubmed, EMBASE, 8oz cups daily for 4 baseline in the green tea groups but not the black tea group, compared to water, months; ↓ 31% (p=0.002). There was modification of effect by genotype.CINAHL, the Cochrane Library, and the National Library of Science C: Black tea or waterand Technology, from inception until February 2010. We used a Key: 8-OhdG 8-hydroxydeoxyguanosine; NS non significant; NSCLC non small cell lung cancer; RCT randomized controlled trial; SCLC small cell lung cancerbroad MeSH and keyword based approach combining clinical (lungcancer) and therapeutic (green tea) search terms. Table 2. Observational Evidence Design Number of Positive/ Highlights of FindingsAll levels of evidence were included. Screening was based on title Neutral/ Negative Studiesor abstract review. Data extraction was piloted in duplicate using Anticancer effects (↓tumor size, incidence), n=14 Prospective 2/ 2/ 0 • 67% ↓risk of lung cancer among those who consumed ≥10 cups per day, RR 0.33 (95%CI 0.11- Increased survival, n=2forms based on standardized reporting guidelines. Cohorts 0.94). Antiproliferative effect, growth inhibition, n=12 • Drinking green tea normalized the rate of sister chromatid exchange in smokers to that of non- Proapoptotic effect, n=9 smokers. Antimetastatic effect, n=7Figure 1. Literature Flow Chart: Case Control 3/ 5/ 1 • In smokers, every 10 mg/d increment in epicatechin consumption ↓lung cancer risk, OR 0.64 Cytotoxcitity, n=2 (95%CI 0.46-0.88), and for every 4 mg/d increment in catechin, OR 0.49 (0.35-0.70). Prevention of dsyplasia or DNA damage, n=8 1050 records selected for initial screen Key: (+) outcome supporting anticancer activity of selenium; (-) outcomes show increased risk or harm associated with selenium; (n) no significant effects; (m) both positive and negative outcomes seen. Inhibition of NF-κB, n=3 881 records excluded after deduplication and initial title/ abstract review Discussion 169 full text articles screened Preclinical evidence Forty-seven studies support the anticancer activity of There is a strong rationale for further investigation of green tea for lung cancer in a green tea, showing growth inhibition and/or antiproliferative effects, clinical setting. Controlled human trials have shown chemopreventive activity for proapoptotic, and anti-invasive and/or anti-metastatic effects. GTE in several premalignant conditions including oral leukoplakia and cervical 104 records excluded - 45 Review/meta-analyses Observational evidence Three studies showed decreased risk of lung cancer dysplasia, as well as in the prevention of colon cancer following polypectomy, and -58 Not relevant to green tea and lung associated with intake of green tea ≥3 - 10 cups daily (1 cup ~200mg EGCG). for prostate cancer in patients with high-grade prostatic intraepithelial neoplasia cancer/ Other --1 not available (HGPIN). Human Evidence There are no controlled clinical trials of green tea for lung cancer. Phase I studies have demonstrated safety of green tea extract (GTE) up Interactions There is preclinical evidence of EGCG augmenting the therapeutic 65 Articles Included for Full Analysis to a maximum tolerated dose (MTD) of approximately 3.0 g/m2/d. This is effect of cisplatin. Green tea should not be used in conjunction with bortezomib due and Review •2 human trials (Phase I) considerably higher than the effective dose used in other cancers (~500- to inhibition of the drug’s anticancer effect. •3 reports of 1 surrogate trial 1500mg/d GTE) or that suggested by observational studies (~250 mg/d There are several human studies Acknowledgements: References: •13 observational •47 preclinical studies catechins). Caffeine content appears be a major factor in contributing to the presently in progress for green tea Funded by the Canadian 1. Laurie 2005 reported adverse effects. in the treatment and prevention of Institutes of Health Research 2. Pisters 2001 (CIHR) 3. Hakim 2003, 2004, 2008 lung cancer.
  • 9. Inositol for Polycystic Ovary Syndrome: A Systematic Review Heidi Fritz ND, MA (1), Kaylee Alton ND(c) (1), Kieran Cooley ND MSc(c) (1,2), Dugald Seely ND, MSc (1,3) ND(c) MSc(c) 1. Department of Research & Clinical Epidemiology, Canadian College of Naturopathic Medicine, Toronto 2. University of Toronto 3. Ottawa Hospital Research Institute College Background ResultsPolycystic ovary syndrome (PCOS) is a complex neuroendocrine Table 1. Clinical Trials of Inositol for the Treatment of PCOScondition affecting between 5-10% of women of reproductive age. Ovarian Insulin Sex ClinicalIt is characterized by a combination of insulin resistance, Ref Population Intervention/ Control Description of Outcomes J score Function Sensitivity Hormones Pregnancyhyperandrogenism, and anovulation; conventional pharmacological RANDOMIZED CONTROLLED TRIALStreatment typically includes the insulin sensitizer metformin, an oral Raffone n= 120 women attempting to I: Myo-inositol 4g + folic acid 400mcg/d x 6mo +* n/a n/a + Inositol: Restoration of spontaneous ovulation in 65%; pregnancy in 30% of these; 2 2010 become pregnantcontraceptive pill, and clomiphene citrate if pregnancy is sought. C:Metformin 1500mg/d Metformin: Restoration of spontaneous ovulation in 50%; pregnancy in 18.3% of these. Constantino n= 42 women I: Myo-inositol 4g + folic acid 400mcg x12-16wk + + + n/a Significant decrease in free and total testosterone; plasma insulin AUC and insulin sensitivity; and 1Inositol is a natural insulin sensitizer with a 6-carbon structure, 2009 C: Folic acid as placebo (same # pills) higher rate of ovulation in the inositol group.related to the family of B-vitamins. The two primary isomers of Papaleo 2009 n= 60 women undergoing IVF I: Myo-inositol 4g + folic acid 400 mcg/d + n/a + none The amount of r-FSH stimulation required to induce ovulation was significantly reduced; peak E2 levels were lower, fewer cycle cancellations, and better oocyte quailty in the inositol group. 2 C: Folic acid onlyinositol are myo-inositol and D-chiro inositol. Inositol exists as Genazzani n= 20 overweight women I: Myo-inositol 2g + folic acid 200 mcg/d x12wk + + + n/a Significant decrease in LH, LH/FSH, prolactin, testosterone, and insulin; improved OGTT; and 2phosphorylated derivatives as well as free form in cell membranes, 2008 C: Folic acid only restoration of menstrual cyclicity in all a- & oligo- menorrheic patients in the inositol grouplwhere it mediates signaling cascades, including insulin signaling. Gerli n= 92 women with oligo- or a- I: Myo-inositol 4g + folic acid 400 mcg/d x16wk +* n/a + n/a No decrease in testosterone. Over 70% of patients receiving inositol established normal ovarian 5 2007 menorrhea and pcos verfied by u/s C: Folic acid as placebo rhythm (3 ovulations/ 16 wk), and significantly fewer inositol patients failed to ovulate c/t controls.We conducted a systematic review on the safety and efficacy of Gerli n= 283 women I: Inositol (form NR) 200 mg/d x 16wk n/a n/a No change in insulin sensitivity parameters. Normal ovarian rhythm established in 30% of inositol 4 +* noneinositol for the treatment of PCOS. 2003 C: Placebo group c/t 18% of placebo. Iuorno n= 20 women with lean phenotype I: D-chiro inositol 600mg/d x 6-8wk + + + n/a Significant decrease in plasma insulin AUC on OGTT, and concomitant 73% decrease in free 5 Methodology 2002 Nestler pcos n= 44 obese women C: Placebo I: D-chiro inositol 1200mg/d x 6-8wk + + + n/a testosterone in the inositol group c/t placebo. 60% versus 20% of the respective groups ovulated. Overall no impact on insulin sensitivity, but subgroup analysis showed improvements among those 4 1999 C: Placebo women with impaired glucose tolerance at baseline. Decrease in testosterone & DHEAS, andTwo independent researchers searched Pubmed from inception increase in SHBG c/t placebo. 19 of 22 compared to 6 of 22 women ovulated.until May 2011, using a broad MeSH and keyword based approach UNCONTROLLED/ NON-RANDOMIZED PROSPECTIVE TRIALScombining clinical (PCOS) and therapeutic (inositol) search terms. Morgante n= 15 women with clomiphene failure Combination of: Inositol 1500mg, Lactoferrin + n/a + NS+ Better follicular maturation in inositol group compared to the matched controls. The inositol group -- 2011 undergoing low dose gonadotropin 100mg, Bromelain 20mg per day, duration NR; had a lower cycle cancellation rate (0 vs 40%, p<0.002) and a non-significantly better pregnancyWe included all human interventional evidence (RCTs and regimen; 15 matched controls Controls received no addition rate: 33.3% vs 13.3%, p=0.18.prospective trials) that administered myo- or D-chiro- inositol to Ciotta n= women undergoing IVF Myo-inositol 4g + folic acid 800mcg/d x 3mo, + n/a n/a n/a Decreased amount of r-FSH required for follicular stimulation. Pregnancy rate NR. -- 2010 OR Folic acid only (non-randomized)patients with PCOS. Initial screening was based on title or abstract Zacche n= 50 women Myo-inositol 4g + folic acid 400mcg/d x 6mo After 6mo, acne resolved in 53% of cases. Hirsuitism resolved in 30% of patients. Total and free -- n/a + + n/areview. Data extraction was piloted in duplicate based on forms 2009 testosterone and basal insulin levels also improved compared to baseline.developed from the CONSORT guidelines. Minozzi n= 46 women with hirsuitism (pcos not Myo-inositol 4g + folic acid 400mcg/d x 6mo n/a + + n/a Improvements in hirsuitism scoring after treatment (p<0.001). Total androgens, LH, and FSH -- 2008 specified, but other endocrine decreased. Insulin resistance as assessed by HOMA model improved significantly.Figure 1. Literature Flow Chart: conditions eg adrenal hyperplasia r/o) Papaleo n= 25 women with infertility Myo-inositol 4g + folic acid 400mcg/d x 6mo or +* n/a + + 88% of women had at least one spontaneous menstrual cycle, and 72% maintained normal ovulatory -- 2007 until pregnancy activity during the study. During the study there were 10 pregnancies, including 2 miscarriages. 125 records selected 132 records selected Key: (+) outcome supporting therapeutic effect of inositol; none no significant effects in either direction; n/a not assessed; AE adverse events; b/o based on; c/t compared to; d/c’d discontinued; J-score JADAD score; NS non significant; pt patients; r/o ruled out; u/s ultrasound; wrt with respect to for initial screen for initial screen 112 records excluded 122 records excluded Discussion Figure 2. Inositol in the Insulin Signaling Pathway • 22 reviews • 22 reviews Phopho-Inositols: • 90 not intervention Inositol may be an effective, natural pharmacological strategy for management of the endocrine • 100 not intervention IP6=Inositol hexakisphosphate trials or trials of trials or trials of and metabolic disturbances characteristic of PCOS. Based on the studies above, inositol IP7=diphosphoinositol pentakisphosphate metformin metformin consistently improves insulin sensitivity and ovarian function, resulting in improvements of patients’ sex hormone profiles. This is important because conventional methods of regulating the menstrual 13 records included 10 records included cycle, such as the oral contraceptive pill, while imposing cyclicity, may also worsen underlying metabolic disturbances such as insulin sensitivity. 13 records after deduplication Four studies (*) reviewed here reported restoration of normal ovarian rhythm in a considerable percentage of participants (range 30-70%). Raffone found that inositol out-performed metformin with respect to effects on ovulatory rhythm and achievement of pregnancy (2010). Three studies of 13 Studies Included for Full Analysis and Review women undergoing assisted reproductive therapy (eg. in vitro fertilization, IVF) found that the • 8 RCTs • 5 Prospective trials addition of inositol resulted in lower requirements for r-FSH (ovarian stimulation), lower rates of cycle cancellation due to high estradiol, and/ or better oocyte maturation. Improvements in acne and hirsuitism, symptoms of hyperandrogenism, were also reported in some studies.
  • 10. Melatonin as Adjuvant Care with and without Chemotherapy A Systematic Review and Meta-analysis Dugald Seely ND, MSc (1), Ping Wu MD, MSc (1), Deborah Kennedy MBA, ND (1), Teresa Tsui ND (1), Edward Mills MPH, MBA, PhD (2) (1) The Canadian College of Naturopathic Medicine; (2) Center for International Health and Human Rights Studies; Simon Fraser Simon UniversityBackground Results Flow diagram of studies examined in this systematic review and meta-analysis Forest plots for symptomatic control Melatonin has a large body of evidence from both 95 potentially relevant abstracts initially collected ORs < 1 indicate an improvement in symptom expression preclinical studies and clinical trials to support its use 24 abstracts immediately excluded as irrelevant in the treatment of multiple cancer types. A major Alopecia (10 trials) Asthenia (13 trials) 71 abstracts selected for further validation 31 studies excluded for the following reasons: concern on the part of medical oncologists is the Peto odds ratio plot Peto odds ratio plot o Not RCT (17) 1997 Lissoni, P 0.69 (0.11, 4.18) 1997 Lissoni, P 0.176 (0.067, 0.460) potential for natural health products like melatonin to o MLT derivative used in intervention (2) o Compared MLT doses at different time points (3) 2003 Cerea, G 1994 Lissoni, P 0.56 (0.05, 5.90) 0.48 (0.05, 4.75) 2003 Cerea, G 1994 Lissoni, P 0.379 (0.048, 3.015) 0.336 (0.045, 2.476) interact with conventional therapies, especially 1999 Lissoni, P 0.234 (0.142, 0.385)Endogenous melatonin production pathway o Comparison between fish oil vs MLT (1) 1999 Lissoni, P 1997 Lissoni, P 0.72 (0.28, 1.84) 0.42 (0.09, 1.96) 1997 Lissoni, P 0.238 (0.077, 0.740) o Ongoing trials (5) 2003 Lissoni, P 0.209 (0.082, 0.536) chemotherapy. 40 full text papers obtained for review 2003 Lissoni, P 0.67 (0.18, 2.47) 2002 Lissoni, P 0.427 (0.240, 0.761) o MLT vs MLT+ MTT (3) 2002 Lissoni, P 0.88 (0.39, 2.00) 2002* Lissoni, P 0.324 (0.258, 0.407) 2002* Lissoni, P 0.80 (0.63, 1.00) 1990 Lissoni, P 0.189 (0.037, 0.967) 1990 Lissoni, P 0.57 (0.12, 2.73) 1994 Brackowski R 0.056 (0.007, 0.457) 1996 Lissoni, P 0.257 (0.070, 0.950) 1994 Brackowski R 0.46 (0.04, 5.27) 22 studies further excluded for the following reasons: combined 0.77 (0.63, 0.95) 1996* Lissoni, P 0.098 (0.021, 0.461) o Treatment in both arms not equal (4) .01 .1 .2 .5 Peto odds ratio (95% confidence interval) 1 2 5 10 2007 Lissoni, P combined 0.350 (0.231, 0.531) 0.302 (0.256, 0.356) o Number of participants in each group not reported (1) .001 .01 .1 .2 Peto odds ratio (95% confidence interval) .5 1 2 5 o Endpoints not clinically relevant (5)Objective 18 studies consisting of 20 separate trials o Studies conducted in patients with tuberous sclerosis (2) Diarrhea (8 trials) Leukopenia (5 trials) included in systematic review o MLT was not evaluated independently of care in control group (9) o The patients were not randomized (1) Peto odds ratio plot Peto odds ratio plot - 13 of the 18 studies included data on 14To explore the issue of potential patient benefit and interaction 1997 Lissoni, P 0.61 (0.14, 2.61) 1997 Lissoni, P 0.31 (0.08, 1.22) separate trials exploring MLT in 2003 Cerea, G 0.60 (0.15, 2.44)in further depth, we conducted a systematic review of the combination with chemotherapy 1994 Lissoni, P 0.95 (0.06, 15.49) 2003 Cerea, G 0.73 (0.11, 4.86)literature to find evidence of melatonin consumption in addition 1999 Lissoni, P 0.63 (0.32, 1.25) Summary of Findings 1999 Lissoni, P 0.56 (0.28, 1.15) 1997 Lissoni, P 0.53 (0.05, 5.31)to chemotherapy in humans with cancer. 1997 Lissoni, P 0.52 (0.10, 2.73) 2002 Lissoni, P 0.78 (0.40, 1.54) 1990 Lissoni, P 0.53 (0.13, 2.08) We found a total of 18 different studies comprising 20 separate clinical trials that fit our inclusion criteria. In one year 2002 Lissoni, P 0.78 (0.37, 1.66) 1994 Brackowski R 1.00 (0.06, 17.62) survival and all measures of tumour response there were statistically significant improvements for those receiving combined 0.67 (0.45, 1.00) combined 0.60 (0.38, 0.94)Methodology .01 .1 .2 .5 1 2 5 10 100 .01 .1 .2 .5 1 2 5 melatonin. The summary OR for survival in all studies at one year was 4.06 (95% CI: 2.97, 5.54) for the groups Peto odds ratio (95% confidence interval) Peto odds ratio (95% confidence interval) randomized to melatonin. In a summary analysis of a subset of 14 trials where chemotherapy was provided to trial Nausea & Vomiting (7 trials) Thrombocytopenia (11 trials)Literature Search: We searched six English electronic participants, the group receiving adjuvant melatonin had an improved odds ratio for survival of 3.50 (95% CI: 2.40, databases (MEDLINE, AMED, Alt Health Watch, Peto odds ratio plot 5.10). In every measure of chemotherapy related adverse events except anemia and cardiotoxicity there were significant Peto odds ratio plot 1997 Lissoni, P 0.76 (0.30, 1.95) 1997 Lissoni, P 0.17 (0.05, 0.65) CINAHL, Nursing and Allied Health Collection: Basic, improvements for those receiving adjuvant melatonin. In no cases were any of the symptoms worsened by the inclusion 2003 Cerea, G 0.82 (0.16, 4.37) 1996 Lissoni, P 1996* Lissoni, P 0.21 (0.05, 0.98) 0.17 (0.03, 0.93) Cochrane Database of Systematic Reviews) and one of melatonin in patient care. 1994 Lissoni, P 0.48 (0.05, 4.75) 1999 Lissoni, P 0.17 (0.08, 0.35) 1999 Lissoni, P 0.73 (0.44, 1.19) 1997 Lissoni, P 0.25 (0.05, 1.33) Chinese language database (CNKI) from inception to 2003 Lissoni, P 0.21 (0.05, 0.87) 1997 Lissoni, P 0.68 (0.23, 2.01) Forest plots for survival and tumour response (all trials vs. only those with chemotherapy) 2002 Lissoni, P 0.18 (0.07, 0.47) 2002 Lissoni, P 0.73 (0.42, 1.27) 2002* Lissoni, P 0.29 (0.19, 0.43) January 2008. 1990 Lissoni, P combined 0.24 (0.04, 1.54) 0.70 (0.51, 0.96) 1990 Lissoni, P 1994 Brackowski R 0.52 (0.05, 5.40) 0.29 (0.03, 2.56) Combined Odds Ratios for all trials 2007 Lissoni, P 0.21 (0.11, 0.38) Combined Odds Ratios for trials with Chemotherapy 0.01 0.1 0.2 0.5 1 2 5 combined 0.23 (0.18, 0.30) Peto odds ratio (95% confidence interval)Inclusion Criteria: To be eligible for inclusion in our .01 .1 .2 .5 1 2 5 10 Peto odds ratio (95% confidence interval) Odds ratio meta-analysis plot [random effects] Odds ratio meta-analysis plot [random effects] systematic review, studies had to have enrolled Chemotherapy was part of therapy in 14 separate clinical trials but was highly variable across the studies. Chemotherapy use consisted of one or more of the 1994 Lissoni, P 10.36 (2.54, 59.16) cancer patients in a prospective study who were 1994 Lissoni, P 10.36 (2.54, 59.16) 1992 Lissoni, P 5.22 (0.90, 53.68) 1999 Lissoni, P 3.45 (1.94, 6.19) 1999 Lissoni, P 3.45 (1.94, 6.19) following: cisplatin (CDDP); etoposide (VP-16); gemcitabine (GEM); oxaliplatin randomly allocated to a treatment regime that 1997 Lissoni, P 3.27 (1.01, 11.20) 1 year (OXA); 5-fluorouracil (5-FU); folates (FA); irinotecan (CPT-11); Mitoxantrone (MTX); 1 year 1997 Lissoni, P 3.27 (1.01, 11.20) survival Carboplatin (CBDCA); Paclitaxel (PTX); epirubicin (Epi); chemoembolization (TACE); 2002 Lissoni, P 3.54 (1.89, 6.65) included melatonin (MLT) in an active group survival 2002* Lissoni, P 2002 Yan, J 5.92 (3.88, 9.28) 1.81 (0.74, 4.44) 2002 Lissoni, P 3.54 (1.89, 6.65) and tamoxifen (TMX). compared to no MLT treatment in a control group. 2002 Yan, J 1.81 (0.74, 4.44) 1994 Lissoni, P 4.60 (0.92, 29.79) (8 trials) (13 trials) 2000 Lissoni, P 55.00 (4.17, 2516.53) Any additional co-interventions had to be identical in 1996 Lissoni, P 5.50 (0.92, 35.57) 2000 Lissoni, P 55.00 (4.17, 2516.53) 2007 Lissoni, P 2.64 (1.70, 4.10) Conclusion both groups, including the use of chemotherapy, 1996 Lissoni, P 11.25 (1.00, 550.98) 1995 Lissoni, P 5.49 (1.17, 27.31) Evidence from randomized clinical trials suggests that melatonin 2007 Lissoni, P 2.64 (1.70, 4.10) radiotherapy, supportive, or palliative care. Studies combined [random] 3.50 (2.40, 5.10) 1995 Lissoni, P 5.49 (1.17, 27.31) combined [random] 4.06 (2.97, 5.54) .5 1 2 5 10 100 1000 1.00E+05 taken by cancer patients orally at night may improve patient that reported only laboratory values rather than odds ratio (95% confidence interval) .5 1 2 5 10 100 1000 1.00E+05 odds ratio (95% confidence interval) survival, not interact negatively with a number of chemotherapy clinical responses were excluded from the analysis. Odds ratio meta-analysis plot [random effects] Odds ratio meta-analysis plot [random effects] agents, and also may result in a reduction of chemotherapy related 1997 Lissoni, P 2.16 (0.11, 130.36) 1997 Lissoni, P 2.16 (0.11, 130.36) side effects.Data extraction: Reviewers conducted data extraction, 2003 Cerea, G 1.14 (0.01, 95.24) 2003 Cerea, G 1.14 (0.01, 95.24) independently, using a standard pre-pilot form, Acknowledgements 1994 Lissoni, P 4.11 (0.38, 207.25) 1994 Lissoni, P 4.11 (0.38, 207.25) Complete 1992 Lissoni, P 1.03 (0.01, 83.53) Complete 1999 Lissoni, P 7.47 (0.93, 339.48) including basic information on patients, data on trial 1999 Lissoni, P 7.47 (0.93, 339.48) Response 1997 Lissoni, P 2.18 (0.11, 132.23) 1997 Lissoni, P 2.18 (0.11, 132.23) Response CCNM would like to acknowledge the generous support of the Lotte 2003 Lissoni, P 3.26 (0.25, 174.18) quality, protocol, and outcomes assessed. Clinical 2003 Lissoni, P 3.26 (0.25, 174.18) (11 trials) 2002 Lissoni, P 4.29 (0.41, 213.54) 2002 Lissoni, P 4.29 (0.41, 213.54) (10 trials) & John Hecht Memorial Foundation. outcomes assessed included: survival, complete and 2000 Lissoni, P 1.14 (0.01, 95.24) 2000 Lissoni, P 1.14 (0.01, 95.24) 2007 Lissoni, P 2.44 (0.78, 9.01) partial response, stable disease, alopecia, anemia, 2007 Lissoni, P 2.44 (0.78, 9.01) 1995 Lissoni, P 1.11 (0.01, 90.84) 1995 Lissoni, P 1.11 (0.01, 90.84) asthenia, cardiac symptoms, diarrhea, fever, combined [random] 2.66 (1.39, 5.06) combined [random] 2.53 (1.35, 4.75) .01 .1 .2 .5 1 2 5 10 100 1000 .01 .1 .2 .5 1 2 5 10 100 1000 leucopenia, nausea, vomiting, thrombocytopenia, odds ratio (95% confidence interval) odds ratio (95% confidence interval)
  • 11. Selenium and Lung Cancer: A Systematic Review Heidi Fritz ND, MA (1), Deborah Kennedy MBA, ND (1,2), Dean Fergusson PhD (3), Rochelle Fernandes MSc, ND(c) (1,2), Kieran Cooley ND, MSc(c) (1,2), Fergusson MSc, ND(c) MSc(c) Andrew Seely MD FRCPC (3), Raimond Wong MD, FRCPC (4), Stephen Sagar MD, FRCPC (4), Dugald Seely ND, MSc (1,3) Sagar 1. Department of Research & Clinical Epidemiology, Canadian College of Naturopathic Medicine, Toronto 2. University of Toronto 3. Ottawa Hospital Research Institute 4. Juravinsky Cancer Center College Background ResultsSelenium is an essential trace mineral with antioxidant activity Table 1. RCTs and Human Surrogate Studies Table 2. Observational Evidencemediated through its ability to increase glutathione peroxidase J Design Number of Positive/ Highlights of Findings Ref Population Intervention/ Control Outcomes +/-activity and incorporate into various selenoproteins. Recently the Score Neutral/ NegativeSelenium and Vitamin E Cancer Prevention Trial (SELECT) reported Primary Prevention Studies Inverse relationship b/w urinary excretion of procarcinogenic lipidno effect of selenium on prostate cancer risk, raising controversy 1 SELECT Trial I: Selenomethionine 200mcg/d x 5.45y OR Selenium had no significant effect on lung cancer alone (RR 1.12, 95%CI 0.73-1.72) or in combination n 2 Prospective Cohorts 2/ 0/ 0 peroxidation product 8-isoprostaglandin F2α and both plasma n= 35,533 healthy menover use of selenium for cancer in general. 4 study arms α-tocopherol 400IU/d OR with vitamin E (RR1.16, 95%CI 0.76-1.78). selenium status and fruit and vegetable consumption. Both C: Placebo No effect on all cause mortality (p>0.15). Inverse relationship b/w toenail selenium and rates of lung cancer.Over 50% of lung cancer patients undergoing radiation therapy use 2a NPC Trial I: Selenium as selenized At 6.4y, ↓risk of lung cancer, RR 0.47 (95%CI +/ 5 Case Control 13/ 7/ 2 Inverse relationship between serum selenium and lung cancer risk.CAM, and 12% report using selenium supplements, however there b n= 1312; history of non yeast 200 mcg/d + beta 0.22-0.98), as well as total cancer incidence and m This effect was evident at serum levels <40-50 mcg/L (↑risk) and >60-80 mcg/L (↓risk). One study showed increased risk at >90 c melanoma skin cancer carotene 15mg + α- mortality, and all cause mortality.has been no knowledge synthesis around use in lung cancer. tocopherol 30mg x 4.5y At 7.4y, a protective effect was still seen in those mcg/L, suggesting the existence of a U shaped curve.Supported by the Canadian Institutes of Health Research (CIHR), we C: Placebo with lower baseline selenium status, and NS ↑risk Cross-sectional 2/ 0/ 1 Serum selenium and GSH Px activity were higher in lung cancer among those with higher baseline selenium status.conducted a systematic review of selenium for lung cancer. patients in three studeis, but lung tissue selenium and GSH Px activity were higher in cases in two studies. 3 n= 28,584 residents of I: Selenium 50 mcg/d as No significant effect on lung cancer incidence, HR n 4 Linxian China selenium yeast x5.25 y 0.98 (0.71-1.35). Methodology Secondary Prevention C: Placebo Figure 1. Mechanisms Supported by Preclinical EvidenceWe searched the following electronic databases for evidence 4 ECOG Trial I: Selenized yeast 200 No significant effects overall on survival or second n 2pertaining to selenium and lung cancer: Pubmed, EMBASE, n= 1561 resected NSCLC mcg/d x4y primary tumor. NS ↑survival among small subset of never smokers, 87 vs 83% at five years. patients C: PlaceboCINAHL, the Cochrane Library, and the National Library of Scienceand Technology, from inception until August 2009. We used a Treatmentbroad MeSH and keyword based approach combining clinical (lung 5 n= 41 Chinese patients w I:Selenium 4000 mcg Selenium ↓need for blood transfusions (p<0.05) + 1 cancer, 27 w lung cancer, (Kappa-selenocarrageenan) and GCSF consumption (p<0.05), ↑WBC counts atcancer) and therapeutic (selenium) search terms. KPS>60% x8d, pre and during cisplatin one time point (p<0.05), ↓cisplatin induced C: Cisplatin only nephrotoxicity (urine NAG and GGT).All levels of evidence were included. Screening was based on titleor abstract review. Data extraction was piloted in duplicate using Surrogate Studiesforms based on standardized reporting guidelines. 6 n=40 healthy Chinese tin I: Selenium enriched cakes ↑plasma and hair selenium, ↑serum GSH Px + 3 Anticancer effect, in vivo, n=12 miners at risk of lung cancer with 300 mcg/d Se from Se- activity,↓lipid peroxide levels, and lymphocyte Effects on redox status, glutathione, or thioredoxin activity, n=10 enriched malt x1yr DNA damageFigure 1. Literature Flow Chart Proapoptotic effects, n=8 C: Non enriched cakes Antiproliferative/ growth inhibitory effects, n=7 7 n=19 Chinese cancer I: Selenium 100 mcg/d as Improvement in ex vivo markers of neutrophil + 2 Cytotoxic effects, n=6 3494 records selected for initial screen patients cancer, 11 with selenium yeast x14 days function. resected lung cancer, Anti-metastatic, anti-invasive effects, n=4 C: Yeast only KPS>90% Increase in survival, n=2 3268 records excluded after deduplication Key: (+) outcome supporting anticancer activity of selenium; (-) outcomes show increased risk or harm associated with selenium; (n) no significant effects; (m) both positive and negative outcomes seen; Immune potentiating effects, n=1 and initial title/ abstract review GGT gamma glutamyl transferase; NAG N-acetyl-b-D-glucosaminidase; NS non significant; SPGT serum glutamic pyruvic transaminase Ambiguous or pro-carcinogenic effects, n=3 226 full text articles screened Discussion 96 records excluded Preclinical evidence supports the anticancer activity of selenium, in Observational findings show increased risk of lung cancer both among those with • 10 in non lung cancer models • 9 related to effects on glutathione only; particular through antioxidant, antiproliferative, and proapoptotic effects. lower and those with higher selenium levels, and reduced risk in those with moderate animal pharmacokinetics, or gene therapy Human Evidence Two of five RCTs found benefit from selenium on lung selenium status, a U-shaped curve. • 3 observational studies of diet only • 2 Not English cancer. In the Nutritional Prevention of Cancer (NPC) trial, there was a Observational evidence has also found an association between increased serum • 72 Not relevant significant overall decrease in risk of lung cancer and total cancer incidence at selenium and risk of diabetes, and this has been corroborated by findings of the NPC 130 Articles Included for Full Analysis and Review 6.5 years. Upon extended follow up, this effect was strongest in those with trial, in which significantly more of the treatment group developed diabetes, HR 1.55 • 7 reports of 5 RCTs serum selenium ≤105.2 ng/mL (=mcg/L) had reduced risk of lung cancer (RR (95%CI 1.03-2.33), and SELECT (non-significant). Acknowledgements: Funded by the Canadian • 2 biomarker trials •15 human trials related to Interactions 0.51, 95%CI 0.32-0.81), while those with serum selenium >121.6 ng/mL had Selenium may be effective for prevention of lung Institutes of Health Research (CIHR) References: • 29 reports of 26 observational studies non significantly increased risk, RR 1.20 (0.77-1.86). cancer in those with lower selenium status, but at 1. Lippman 2009 4. Karp 2010 [Conf. Proc.] • 41 preclinical related to Efficacy 2a. Clark 1996 5. Hu 1997 •36 preclinical related to Selenium Interactions One trial found benefit from selenium on bone marrow function and cisplatin present should not be used as a general strategy b. Duffield-Lillico 2002 6. Yu 1990 induced nephrotoxicity. Other trials reported reduction of lymphedema and for cancer prevention. Selenium deserves further c. Reid 2002 3. Kamangar 2006 7. Xu 1990 improved response to chemotherapy. study for use alongside chemotherapy.
  • 12. Vitamin A and Retinoid Derivatives for Lung Cancer A Systematic Review Heidi Fritz ND, MA (1), Deborah Kennedy MBA, ND (1,2), Dean Fergusson PhD (3), Steve Doucette MSc (3), Rochelle Fernandes MSc, ND(c) (1,2), Kieran Cooley Fergusson ND(c) ND, MSc(c) (1,2), Andrew Seely MD, FRSCPC (3), Stephen Sagar MD, FRCPC (4), Raimond Wong MD, FRCPC (4), Dugald Seely ND, MSc (1,3) MSc(c) (4), 1. Department of Research & Clinical Epidemiology, Canadian College of Naturopathic Medicine, Toronto 2. University of Toronto 3. Ottawa Hospital Research Institute 4. Juravinsky Cancer Centre College Background ResultsLung cancer accounts for 12% of cancers globally and is the most Table 1. RCTs for Treatment of Lung Cancer Table 3. Observational Evidencecommon cancer second only to non-melanoma skin cancer. Lung Ref Population (n) Intervention / Control Outcomes J score Type Protective Increased Risk No Effectcancer is the leading cause of cancer mortality, with an estimated 1 Stage III/IV breast CA, lung (26), other I : 13CRA 0.5 mg/kg + IL-2 1.8 MIU for one year. 1ary: Immuno. parameters, VEGF. ↑ lymphocyte, NK 1 Effect cancers (112); maintenance therapy. C: IL-2 only counts, VEGF; trend to ↑ PFS (p=0.185). NS: OS.159,390 deaths in 2009 in the United States alone. Prospective 3 0 4 2 Stage IIIB with pleural effusion or IV I : Bexarotene 400 mg/m2/d (actual mean dose 323 No difference in survival between groups, but overall 2 (n=7) NSCLC; adjuvant therapy. mg/m2)+ cisplatin/ vinorelbine for ~3 cycles (12 wk). response rates were significant ↓in the bexaroteneDespite reported antiproliferative activity of vitamin A and C: cisplatin vinorelbine only group, 16.7% vs 24.4% (p=0.022). Retrospective Case 12 2 11widespread use for cancer, there is no comprehensive synthesis of 3 Stage IIIB or IV NSCLC; adjuvant therapy. I : Bexarotene 400 mg/m2/d (actual mean dose 315 NS effects. Survival and response rate tended to be ↓ in 2 Control Cross-sectionalits safety and efficacy in lung cancer. To address this issue we mg/m2), antilipid therapy, carboplain/ paclitaxel ~4 bexarotene group (p=0.2, 0.061, 0.24 respectively), but (n=25) cycles (12 wk) C: paclitaxel carboplatin only ↑ survival in subgroup (p=0.014)conducted a systematic review of vitamin A and related retinoids 4 Stage I-IV SCLC, responded to platinum I : 13CRA 1 mg/kg/d + IFN-α2a x 12 mo, OR NS diff. in parameters: chemotherapy response duration, 2for the treatment and prevention of lung cancer as well as chemotherapy; maintenance therapy. trophosphamide C: No maintenance therapy survival, 1yr survival, TTP, time to deathassessing for possible interactions with conventional cancer Figure 2. Mechanisms Supported by Preclinical Evidence 5 Stage IIIB with pleural effusion, stage IV, I : Bexarotene 300 or 600 mg/m2 daily following NS effect on tumor response or median survival. Dose 4therapies. or recurrent NSCLC; maintenance therapy platinum based chemo, until progression effect on TTP of 128, 82, and 56 days in the 600 mg, C: Chemotherapy alone 300 mg, and placebo groups (p=0.56). Methodology Table 2. RCTs for Primary and Secondary Prevention of Lung CancerWe searched the following electronic databases for all levels of Ref Population (n) Intervention / Control Outcomes J Scoreevidence pertaining to vitamin A and lung cancer: Pubmed, 6 n=18,314 smokers, former smokers, or I: 25,000 IU/d retinyl palmitate + 30 mg Beta ↑ Risk: overall RR 1.28 (1.04-1.57); RR asbestos 1.40 4 workers exposed to asbestos carotene x 5-8 years (up to 11 if in pilot) C: placebo (0.95-2.07) RR current smoker 1.42 (1.07-1.87)EMBASE, CINAHL, AltHealthWatch, the Cochrane Library, and the 7 n=1024, former asbestos workers (21% I: 25,000 IU/d retinyl palmitate for approx >400 days ↓mesothelioma in retinol group RR 0.24 (0.07-0.86). 2National Library of Science and Technology, from inception to July current smokers) C: beta carotene 30 mg/d NS difference in lung CA risk RR 0.66 (0.19-2.32).2009. We used a broad MeSH and keyword based approach 8 n= 28,584 residents of Linxian China I: 2(4) factorial design: 8 tx arms, half received retinyl No significant reduction in mortality from lung cancer HR 4combining clinical (lung cancer) and therapeutic (vitamin A) search palmitate (25,000 IU/d) + zinc (22.5 mg/d) in 0.82 (0.59-1.14) for group receiving retinol and zinc. Growth Inhibition/ Antiproliferative Effect, n=33 combination with other arms x 5.25 yrs C: placeboterms. Two independent searches were conducted. Proapoptotic, n=15 9 Stage Ia resected NSCLC pts (181). I : 300,000 IU retinyl palmitate/d x 12 mo At 5 yr, 64 vs 51% were disease free (RR 1.4, 95% CI 2 Anticancer Effect, n=14All levels of evidence were included. All types of lung cancers Adjuvant therapy. C: no treatment 0.80-1.66, p=0.054); significant (p=0.038) when adjusted for primary tumor classification. 89 vs 80% of pts were Anti-metastatic, anti-angiogenic, anti-invasive, n=7(SCLC, NSCLC, mesothelioma) were included. Screening was free of SPT (lung/ H&N/ bladder) (RR 1.96, 1.00-3.84, Cytotoxic, n=3based on title or abstract review. Data extraction was piloted in p=.045).duplicate using forms based on standardized reporting guidelines. 10 NSCLC and H&N cancer pts, majority I : Arm 1: 300,000 IU/d retinyl palmitate x 1yr, then NS differences in overall survival or event-free survival 3 Co-Carcinogenic, n=1 Stage I, who had been treated curatively, 150,000 IU/d for 2nd year; between groups. mostly with surgery w/wo radiation Pro-angiogenic, n=1Figure 1. Literature Flow Chart: (2573). Majority smokers. Arm 2: 600mg/d NAC; Arm 3: NAC +vitA C: no treatment Studies Included in Efficacy Analysis Studies Included in Interactions Analysis 11 Stage I NSCLC with complete resection; I : Range b/w 30 mg/d to 10 mg q2d isotretinoin for 3 NS ↑ risk of SPT, HR 3.14 (0.63-15.55); risk of 4 currently ds free (1166). years recurrence HR 0.44 (0.15-1.27); and risk of mortality HR 7257 records 2575 records C: placebo 0.036 (0.10-1.37). for initial screening for initial screening 6961 records excluded 2361 records excluded Discussion after deduplication and after deduplication and title/ abstract review title/ abstract review Preclinical evidence largely supports the anticancer activity of vitamin A, Adverse Events The most common side effects observed in controlled clinical trials were particularly through growth inhibitory, antiproliferative, proapoptotic, and Grade I-II mucocutaneous symptoms (including dry skin, rash, conjunctivitis, and chelitis), 296 Full text records screened 214 Full text records screened anticancer effects. reversible hypothyroidism, hypercholesterolemia, and elevated liver enzymes. 155 records excluded 107 records excluded Human Evidence The majority of RCTs failed to show any benefit. There Interactions Night blindness causing treatment delays were reported with appears to be a lack of evidence to support the use of vitamin A for the combination of fenretinide and cisplatin or paclitaxel. Retinoic Acid Syndrome with 248 Articles Included for Data Extraction & Analysis 11 RCTs treatment and prevention of lung cancer. The Beta Carotene and Retinol pulmonary complications was seen in leukemia. Night blindness was a side effect 26 Phase I/ II trials Efficacy Trial also demonstrated that vitamin A increases lung cancer in high of 13 cis retinoic acid treatments. Acknowledgements: Funded by the Canadian 5 Surrogate studies risk populations. This negative result may be explained by the conditional Institutes of Health Research (CIHR) 32 Observational antioxidant theory, wherein the activity of an antioxidant depends on its redox Clinical Implications Current evidence References: 6. Omenn 1996 67 Preclinical studies 1. Recchia 2005 7. deKlerk 1998 107 Interactions studies potential in relation to other pro- and anti- oxidants in its environment. Under does not support use of vitamin A as a 2. Ramlau 2008 8. Kamangar 2006 conditions of high oxidative stress such as smoking, certain antioxidants may safe, effective preventative agent nor 3. Blumenschein 2008 9. Pastorino 1993 4. Ruotsalainen 2000 10. vanZandwijk 2000 act as conditional pro-oxidants. treatment agent for lung cancer. 5. Rizvi 2006 11. Lippman 2001
  • 13. Vitamin C and Lung Cancer: A Systematic Review Heidi Fritz ND, MA (1), Deborah Kennedy MBA, ND (1,2), Dean Fergusson PhD (3), Sarah Vadeboncouer, ND (1), Kieran Cooley ND MSc(c) (1,2), Fergusson Vadeboncouer, MSc(c) Andrew Seely MD, FRCPC (3), Raimond Wong MD, FRCPC (4), Stephen Sagar MD, FRCPC (4), Dugald Seely ND, MSc (1,3) 1. Department of Research & Clinical Epidemiology, Canadian College of Naturopathic Medicine, Toronto 2. University of Toronto 3. Ottawa Hospital Research Institute 4. Juravinsky Cancer Center College Background ResultsThe anticancer effects of vitamin C, or ascorbic acid, were first Table 1. Human Trials of Vitamin C in Lung Cancer Patients Figure 2. Lung Cancer Related Preclinical Mechanismspublicized in a case series of 50 terminal cancer patients in the Ref Population Intervention/ Control Outcomes +/- J score1970s (1). Although vitamin C is an antioxidant, it can act as a pro- RANDOMIZED CONTROLLED TRIALSoxidative, cytotoxic agent through the generation of intracellular Prevention – Oral Vitamin CH2O2 in cancer cells, which it preferentially targets at high plasma 3 n= 28,584 residents of Linxian I: Vitamin C 120mg/d + molybdenum No impact on risk of lung cancer, HR 1.01 (95% CI 0.73-1.39). n 4concentrations. Recently the Canadian Medical Association Journal China 30mcg/d in combination with other armspublished 3 cases of remission in cancer patients treated with 2(4) factorial design, x 5.25y; C: Placebointravenous vitamin C (2), renewing interest in this therapy. Treatment – Oral Vitamin CSupported by the Canadian Institutes of Health Research (CIHR), we 4 n= 138 patients with advanced I: Paclitaxel +carboplatin chemo PLUS No significant impact on Response Rates (37% with vitamin C c/t 33% without, p=0.28); n 3conducted a systematic review on the safety and efficacy of oral NSCLC undergoing antioxidants including VitC 6.1g daily; Survival at 2y (15.6% c/t 11.1%, p=0.20); or other measures of survival (p=0.20). Anticancer effect in vivo, n=9 chemotherapy C: Identical chemotherapy only Antiproliferative effect or growth inhibition, n=5and intravenous vitamin C therapy in patients with lung cancer. 5 n=102 NSCLC patients who I: Vitamin C 3-5 g/m2 per day No significant impact on Response rates or median survival, p values not reported. n 2 Antimetastatic effect, n=3 failed one of the other 7 C: VM-26 (teneposide) 67 mg/m2 IV q Cytotoxicity, preferential to tumor cells, n=2 Methodology chemotherapy arms PROSPECTIVE, UNCONTROLLED TRIALS wk Protection against DNA damage, n=2 Procarcinogenic effect (w tobacco smoke), n=1We searched the following electronic databases for evidence Treatment – Intravenous Vitamin C No significant effects or mixed effects, n=8pertaining to vitamin C and lung cancer: Pubmed, EMBASE, 6 n= 24 patients with advanced I: IV ascorbic acid in Ringer’s lactate in No obvious impact on tumor response: no complete or partial responses, disease stabilization + n/a solid tumors (lung=1) escalating doses from 400-1500 in 2 patients.CINAHL, the Cochrane Library, and the National Library of Science mg/kg 3x/wk. Oral VitC on non- Significant improvement in physical function in the 0.4g/kg group, p<0.01 c/t baseline (FAACT- Table 2. Summary of Observational Evidenceand Technology, from inception until February 2010. We used a infusion days. For avg 10 wk. G questionnaire). In the higher dose groups, there was stabilization of physical function score, Design Positive/ Highlights of Findingsbroad MeSH and keyword based approach combining clinical (lung such that there was no deterioration over the course of the study. Neutral/ Negative 7 n= 39 stage IV cancer patients I: IV ascorbic acid 10g 2x/wk plus Response rates not reported. There was significant improvement in global QOL c/t baseline, + n/acancer) and therapeutic (vitamin C) search terms. (lung=7) 4g/d oral vitamin C x 1wk p=0.001 (EORTC questionnaire), as well as on the function scales (p<0.05 for all) and most of Studies the symptoms scales (p<0.05). Prospecti 1/ 6/ 0 Only one study found an associationAll levels of evidence were included. Initial screening was based on ve between low vitamin C intake and 8 n= 24 terminal patients with I: IV sodium ascorbate at 1 of 5 daily No obvious impact on tumor response: disease progression n=23, disease stabilization n =1. n n/atitle or abstract review. Data extraction was piloted in duplicate gastrointestinal cancers, some doses between 150-710 mg/kg Studies increased risk of lung cancer, RR 2.02 (1.15-3.54).using forms based on standardized reporting guidelines. with lung metastases (equivalent to 10-50 g/d for 70kg) Retrospe 9/ 0/ 0 All studies comparing plasma or other Treatment – Oral Vitamin CFigure 1. Literature Flow Chart: ctive/ markers of vitamin C status found 9 n= 59 patients with advanced I: Vitamin C 5g/d in 3 divided doses No efficacy outcomes reported; pharmacokinetic study. Oral vitamin C treatment results in over n n/a Cross- significantly reduced levels among NSCLC or bladder cancer a 3-fold increase in blood levels of ascorbic acid. sectional lung cancer patients. 1237 records selected for initial screen Key: (+) outcome supporting anticancer activity of vitC; (-) outcomes show increased risk or harm associated with vitC; (n) no significant effects; (m) both positive and negative outcomes seen; AE adverse events; c/t compared to; d/c’d discontinued; NS non significant; pt patients; QOL quality of life; wrt with respect to 1101 records excluded after deduplication and initial title/ abstract review Discussion 136 full text articles screened Preclinical evidence most strongly supports the in vivo anticancer effects Safety of IVC IVC is contraindicated in patients with glucose-6-phosphate 87 records excluded and antiproliferative effects of vitamin C in lung cancer. Several studies have dehydrogenase deficiency due to risk of hemolysis; therapy must be preceded by showed that vitamin C may potentiate the effects of chemotherapy: reducing appropriate screening. In patients with advanced cancer, there is risk of acute • 26 reviews • 61 not relevant to vitamin C and lung vincristine resistance by increasing drug uptake, reducing proliferation of hemorrhage and tumor necrosis; therefore in such cases therapy should begin at low cancer doxorubicin resistant cells, and augmenting the anticancer effect of mitomycin- dosages with incremental increases. There has been some concern raised regarding C and 5-fluorouracil. the antioxidant effect of vitamin C interfering with pro-oxidative chemotherapies; a solution proposed by Seely (10) is that the administration of IVC be at least 5 half- 49 Studies Included for Full Analysis and Review Human Evidence There is a lack of high quality evidence around the use of life’s apart from the chemotherapies, since this is the time required to eliminate a • 3 RCTs of oral vitamin C • 1 Biomarker trial of oral vitamin C intravenous vitamin C for the treatment of lung cancer. RCTs of oral vitamin C drug from the body, and ensuring an appropriate washout period between therapies . • 1 Prospective trial of oral vitamin C have shown no significant impact on risk of lung cancer, tumor response Acknowledgements: Funded by the Canadian • 3 Prospective trials of intravenous vitamin C rates, or survival. Uncontrolled trials of intravenous vitamin C (IVC) have found In view of the promising results reported by many Institutes of Health Research (CIHR) • 16 Observational that IVC can improve quality of life, including physical function and cancer clinicians and as well as in the literature through References: 6. Hoffer 2008 • 25 Preclinical 1. Cameron 1974 related symptoms, however, to date there are no human trials showing impact case series, intravenous vitamin C deserves further 2. Padayatty 2006 7. Yeom 2007 8. Riordan 2005 to response rates or chemotherapy outcomes in lung cancer patients. study in controlled human trials. 3. Kamangar 2006 4. Pathak 2005 9. Greco 1982 10. Seely 2007 5. Creech 1981
  • 14. Vitamin D and Lung Cancer: A Systematic Review Heidi Fritz ND, MA (1), Deborah Kennedy MBA, ND (1,2), Dean Fergusson PhD (3), Rochelle Fernandes MSc, ND (cand) (1,2), Kieran Cooley ND, MSc (1,2), Fergusson (cand) Andrew Seely MD, FRCPC (3), Raimond Wong MD, FRCPC (4), Stephen Sagar MD, FRCPC (4), Dugald Seely ND, MSc (1,3) 1. Department of Research & Clinical Epidemiology, Canadian College of Naturopathic Medicine, Toronto 2. University of Toronto 3. Ottawa Hospital Research Institute 4. Juravinsky Cancer Center College Background ResultsVitamin D is a promising new area in cancer research. Low levels of Table 1. RCT and Phase I & II Studies of Vitamin D for the Treatment and Prevention of Lung Cancer Figure 2. Preclinical Mechanismsvitamin D have consistently been associated with higher risk of Ref Population Intervention/ Control Outcomes +/- J scoreseveral cancers in the medical literature, and altered vitamin D RCTsmetabolism has been reported in lung cancer patients. There is 1 n= 1180 post I: Vitamin D3 1100 IU + 1400- Incidence of cancer in each group was: 13 in the calcium +D group, 17 in the + 4growing consensus that the serum vitamin D levels [25(OH)D] menopausal women from 1500 mg calcium/d OR calcium alone group, and 20 in the placebo group. Cases of lung cancer were 1, Nebraska 3, and 3 respectively.traditionally viewed as adequate for bone health are much lower 3 study arms Calcium alone X 4yr Relative risk of total cancer was 0.402 (95% CI 0.20-0.82) for the calcium +D C: Placebothan that required for other areas of health, including cancer group, while that for calcium alone was non-significant.prevention. Since individuals residing in northern latitudes are at Regression analysis showed that for every 25 nmol (10 ng/mL) increase in serum 25(OH)D there was a 35% reduced risk of cancer. Antiproliferative effect, growth inhibition, n=4increased risk of vitamin D insufficiency [25(OH)D <75 nmol/L], No serious AE: kidney stones were reported, 1 in calcium+D, 3 in calcium only, 1 Proapoptotic effect, n=1supplementation may be an important strategy for the treatment in placebo. Antimetastatic effect, n=6and prevention of cancer. Phase I & II Studies (Uncontrolled) Cytotoxic effect, n=1 2 n= 23 pts with stage III Vitamin D analog Median survival was 95 days, range 19-214 days. n --Supported by the Canadian Institutes of Health Research (CIHR), we or IV adenocarcinoma dihydrotachysterol (DHT) 0.3 Immune stimulating effect, n=3 Approximately 50% of patients experience improvement in:conducted a systematic review of the safety and efficacy of vitamin of the lung mg/d orally in addition to the Fatigue Anticancer effect (chemoprevention, ↓tumor size), n=1 following protocol: Cough, dyspnea and respiratory symptomsD in patients with lung cancer. Retinyl palmitate 5000 IU/d Insomnia All trans retinoic acid 5mg/d Chest and general pain Table 2. Summary of Observational Evidence Methodology Beta carotene 20 mg/d Hemoptysis Melatonin 40 mg/d And this was especially apparent among patients who survived >95 days. Design Number of Positive/ Highlights of Findings Bromocriptine 5mg/d AE consisted of mild GI upset and drowsiness and were managed by adjusting Neutral/ Negative Studies Cyclophosphamide 100 orWe searched the following electronic databases for evidence 200 mg/d doses of melatonin and somatostatin. Prospect 2/ 3/ 0 Among a cohort of early NSCLC patients, those who had ive surgery in the summer had a trend toward better survivalpertaining to vitamin D and lung cancer: Pubmed, EMBASE, Somatostatin 1-3 mg q8-10h SQ Cohorts than those who had surgery in the winter, AHR 0.75CINAHL, the Cochrane Library, and the National Library of Science 3 n= 36 pts with solid Calcitriol + Paclitaxel: There were no dose limiting toxicities observed. No clinically significant n -- (95%CI 0.56-1.01). Those who had both 25(OH)D >15.7 ng/mL or 39.25and Technology, from inception until April 2010. We used a broad epithelial tumors Calcitriol in escalating doses hypercalcemia occurred. There was a wide variation in pharmacokinetic nmol/L plus intake >371 IU vitD3 per day had significantly including lung cancer parameters, and serum calcitriol elevations were not proportional to doseMeSH and keyword based approach combining clinical (lung between 4-38 mcg orally 3d/wk administered and became saturated at 13 mcg TID dosing. better overall survival, AHR 0.64 (0.42-0.98). Paclitaxel 80mg/m2 IV infusioncancer) and therapeutic (vitamin D) search terms. 1x/wk Case 3/ 0/ 0 Serum 25(OH)D levels were significantly lower among lung cancer patients c/t controls, median 21.0 vs 35.0 Control/ 4 n= 16 Japanese pts Vitamin D analog alfacalcidiol Median survival was 45.0 months (range 5-47). A partial response was seen + -- Cross nmol/L. Diagnosis in the summer or fall when serumAll levels of evidence were included. Screening was based on title with stage IV renal cell 1mcg/d + IFN-α 3MIU 3x/wk in 25% of patients (n=4), disease stabilization occurred in 62.5% (n=10), and Sectional 25(OH)D is known to be highest combined with residenceor abstract review. Data extraction was piloted in duplicate using carcinoma with for up to 3 years or until disease progressive disease was seen in 12.5% (n=2). A partial response was seen in in the south east vs northern Norway was associated with 25% reduced risk of death among lung cancer patients. metastases to the lung progression a patient with spindle cell carcinoma which typically carries a poor prognosis,forms based on standardized reporting guidelines. leading to the conclusion that this combination was effective. One pt had to Ecologic 4/ 0/ 0 Lung cancer incidence increases with decreasing UVBFigure 1. Literature Flow Chart: d/c therapy d/t hypercalcemia. Studies exposure (measured as latitude of residence or history of Key: (+) outcome supporting anticancer activity of vitamin D; (-) outcomes show increased risk or harm associated with selenium; (n) no significant effects; (m) both positive and negative outcomes seen; non-melanoma skin cancer). 1760 records selected for initial screen AE adverse events; d/c discontinue; d/t due to; GI gastrointestinal; IFN-α interferon alpha; MIU million international units; pt patients; SQ subcutaneously; TID three times per day Among black Americans, the number of premature deaths per year d/t insufficient UVB was estimated at 240. 1677 records excluded after deduplication and initial title/ abstract review 83 full text articles screened Discussion Preclinical evidence most strongly supports antiproliferative, antimetastatic, Clinical Implications Although the clinical evidence supporting an anticancer effect 54 records excluded and immune stimulating effects of vitamin D in lung cancer models. for supplemental vitamin D in lung cancer patients is sparse, supplementation to • 23 reviews or meta-analyses Human Evidence Only one RCT has been conducted for the treatment or achieve and maintain normal levels appears to be well founded when considered from • 31 not relevant to lung cancer or fish oil prevention of cancer including lung cancer. A modest dose of vitamin D (1100 the perspective of nutritional adequacy. The consensus in the scientific community is or duplicate IU) plus calcium significantly reduced risk of total cancer, however, the number that 25(OH)D levels ≥75 nmol/L (30 ng/mL) or higher define adequacy. An important of cases was insufficient to draw conclusions about effect on lung cancer dose-finding study by Aloia (2008) found that for individuals with serum levels >55 specifically. Although phase I and II trials have shown modest results with use nmol/L, a median dose of 3800 IU/d was required to achieve Acknowledgements: adequacy, while for those with levels <55, a median dose of 5000 Funded byInstitutes of Canadian the 29 Studies Included for Full Analysis and Review of calcitriol (activated vitamin D) and vitamin D analogs, the conclusions that IU/d was required, with considerable inter-individual variation. Health Research (CIHR) • 1 RCT can be drawn are limited by lack of a control arm and use of multiple References: 1. Lappe 2007 • 3 phase I and II trials therapies. In addition to the single RCT, observational evidence forms most of Safety Hypercalcemia is a concern with vitamin D in certain types of 2. Norsa 2007 • 12 observational the basis for use of vitamin D in lung cancer patients, with better survival cancer including small cell lung cancer. These patients should be 3. Muindi 2002 4. Obara 2008 • 13 preclinical associated with higher 25(OH)D and lower levels found among cancer patients. monitored for PTH, 25(OH)D, 1,25(OH)D, and calcium. 5. Aloia 2008
  • 15. Safety and Efficacy of a Compound Natural Health Product in Children with ADHD: A Feasibility Study Kieran Cooley (1,2), Dugald Seely (1), Umesh Jain (3), Anna Taddio (2), Sunita Vohra (4), Heather Boon (2)* 1The Canadian College of Naturopathic Medicine, 2 Leslie Dan Faculty of Pharmacy, University of Toronto 3 Center for Addiction and Mental Health 4 Dept. Medicine, University of Alberta *MSc. Supervisor Figure 1: Participant flow Table 1: Weight-based dose of nutrients in NHP Background Weight (kg) Posology Total Daily Dose Results 90 Inquired Time (12) 25-34 kg 3 tablets / 15 mg zinc day 150 mg magnesium ‘Research’ (10) 30 mg pyridoxine Table 4: Statistically significant changes on Connors 3 Parent (n=21) 150 mg vitamin C • Attention deficit hyperactivity disorder (ADHD) is a chronic neurobehavioral mental health Recent change (7) disorder with functional impairment as a result of concentration/attention or impulsivity/hyperactivity. 34-42 kg 4 tablets / 20 mg zinc Connors T Scores Mean Mean 10 wk Mean Change P value day 200 mg magnesium • An estimated 30-50% of children diagnosed with ADHD do not respond well to conventional stimulant 40 Screened Iron (4) (Clinically significant T Baseline (range) (range) 40 mg pyridoxine medications. (1) Health Care 200 mg vitamin C Score) (range) Provider (4) 42-50 kg 5 tablets / 25 mg zinc • Epidemiological evidence suggests a correlation between nutritional deficiencies (zinc, magnesium and iron) 3 Adverse Events day 250 mg magnesium Inattention T 64.5 56.9 -7.7 <0.001 and the incidence of childhood ADHD. (2) (blood draw) Blood Draw (4) 50 mg pyridoxine (72) (41-86) (38-72) (-18 – 2) • Preliminary evidence suggests that children with ADHD can benefit from nutritional supplementation, 250 mg vitamin C possibly by correcting relative nutrient deficiencies. (3,4,5) 28 Enrolled Hyperactivity T 72.7 62.5 -10.2 <0.001 50-58 kg 6 tablets / 30 mg zinc Incomplete Data (4) day 300 mg magnesium (72) (39-88) (34-82) (-21 - -1) 1 Adverse 60 mg pyridoxine Withdrew Assent (2) 300 mg vitamin C DSM IV Inatten T 64.0 53.1 -7.9 <0.001 Reaction (rash) Study Objectives Lost to Follow-up (1) >58 kg 7 tablets / day 35 mg zinc 350 mg magnesium (72) (39-84) (39-69) (-25 – 1) 21 Completed 70 mg pyridoxine DSM IV Hyper T 68.2 59.3 -9.0 <0.001 350 mg vitamin C (72) (32-80) (30-71( (-21 – 0) Primary objective • To determine the feasibility of conducting a randomized control trial designed to evaluate the safety and efficacy of • Statistically significant reductions occurred on all Connors 3 scores indicating symptom improvement compared to a compound NHP to improve clinical symptoms in children with ADHD. The 4 criteria used for feasibility assessment are: population norms. 1) Consent and enroll 30 participants in a 3 month period 2) Retain 20 of 30 for the duration of the study Results 3) Successfully collect 80% of data for analysis and 4) Observe >25% improvement on measures of efficacy • Clinical cutoff points (Connors 3 Parent DSM-IV criteria): 2 no longer met DSM-IV criteria for Inattention, 8 for relating to the severity of ADHD symptoms. Hyperactivity/Impulsivity and 4 no longer met combined Inattentive:Hyperactive/Impulsive. Table 2: Participant demographics (n=28) Secondary objectives Mean age (range) 8.7 years (7-11) • To generate preliminary data of the safety and efficacy of a compound NHP in children with ADHD. •Of the 90 inquiries, 45 (50%) came from physician Recruitment Gender 4 female, 24 male referral (psychiatrist and ND), 17 (19%) from Discussion & Conclusion • To generate pilot data on the ability of a compound NHP to correct apparent nutritional deficiencies in zinc Concurrent Rx 6 (4 dexedrine, 1 atomoxetine, 1 information talks, 16 (18%) from a clinical trial Recruitment is feasible for the study as designed, although concessions were made regarding baseline ferritin and iron as a & magnesium in children with ADHD. management methylphenidate) registry, 7 (8%) from ADD support groups and 5 confounding factor – despite these theoretical concerns, iron status did not appear to be well correlated with response to (6%) from ‘word of mouth’. treatment in the study population. Mean weight (range) 36.4 kg (24.5 - 50.2) • To generate pilot data on correlations between deficiencies in zinc and/or magnesium and severity of clinical symptoms •44% of all inquiries resulted in screening. • One of the most significant obstacles to recruitment and retention of participants is related to the blood draw, both through of ADHD for future investigation. Participant’s dose 3 pill/day: n=8 apprehension and also through nutritional Methods 4 pills/day: n=14 • Reasons given not to participate: inability to • Future recruitment strategies should focus on casting a broad net and finding physicians who are willing/able to champion 5 pills/day: n=5 commit to time (12), reticence to participate in recruitment efforts for appropriate potential participants. 6 pills/day: n=1 research (10) and recent changes to Mean baseline ferritin 35.3 ug/L (12-79) medication/diet (7). Data collection: 93% of data (questionnaires and blood samples) was able to be collected. •10-week open label feasibility study on the safety and efficacy of weight-based dosing of a compound NHP containing •Low (12-22): n = 6 zinc, magnesium, vitamin B6 (prydoxine HCl) and vitamin C (calcium ascorbate) to treat children (age 6-12) with ADHD. (range) • Despite redundancy in the content of the SNAP-IV and Connors 3 questionnaires, these measure distinct outcomes and should •Medium (23-37): n= 11 •70% of participants that were screened were able be included in future research studies. •High (>37.): n= 10 Inclusion Criteria: to be included in the study. ADD classification Inattentive: n=5 • Baseline serum ferritin was negatively correlated with baseline ADHD severity based on SNAP score (r=-0.153) suggesting • Children age 6-12 with uncomplicated ADHD as diagnosed by structured clinical interview: DSM-IV for (SNAP) Hyperactive/Impulsive: n=13 that participants with lower iron status may experience more severe symptoms of ADHD. •Serum ferritin was the most frequent criteria for children (KSAD) Combined: n=10 excluding participants. 7 participants were excluded • Subjectively, the FFQ did not prove to be a sensitive measure of dietary status OR change in this population. Utility of this • Willing and able to provide informed consent/assent Mean baseline Zn 10.8 ug/L (8.5-15.4) prior to an amendment at 3 months which reduced questionnaire in future studies is questionable. (range) •Low (<11): n = 12 the ferritin level for exclusion from <30 ug/L to <12 Exclusion Criteria: •Medium (11-13): n= 11 ug/L. Safety and Compliance: Medication consumption and self-rated tolerability was >80%. 4 participants commented on mild • Comorbid mental health disorder (e.g. oppositional defiant disorder •High (>13): n= 4 dissatisfaction with the taste (‘metallic’) or consistency (‘chalky’). conduct disorder) as diagnosed by KSAD Mean baseline Mg 2.2 mmol/L (1.8-2.8) • Word of mouth, information talks and physician • 1 mild, resolving rash occurred during the study, indicating that the dose and duration of use these nutrients in the study was •Serum Ferritin <12 ug/L (range) •Low (<2.2): n = 10 referral had the highest enrollment success ratio •Medium (2.2-2.4): n= 11 both safe and sustainable and may have some use clinically. (inquired:enrolled).Recruitment •High (>2.4): n= 6 • Safe, effective means of collecting blood in the population of ADHD children should take into consideration physical,•Parents of children diagnosed with ADHD were sought through referrals from a child psychiatrist at the Centre behavioural and psychological means of decreasing adverse events which may include topical anaesthetic, distraction, timingfor Addiction and Mental Health, and from naturopathic doctors. Table 3: Statistically significant changes on SNAP and nutrient serum and set-up of venipuncture (including choice of personnel completing the procedure).• Poster and email advertisements were circulated through various local ADD/ADHD support networks and a levels (n=21) Efficacy: Mean improvements on Connors 3 (-28.9%), and SNAP-IV total (-26.4%) were clinically meaningful (p<0.001) but didtalk was given at a local ADHD conference. not correlate strongly with changes in serum zinc (r=-0.059) or RBC Mg (r=-0.202). Outcome Means Score Means Score 10 Mean Change P value • Considerable variation on measures of efficacy and nutrition make generalizable assessment challenging – observations from•Following informed consent and child assent, all children were administered the KSAD, and baseline outcome Baseline wk (range)measures. this study indicate that the study NHP had somewhat better efficacy in participants with more severe hyperactivity symptoms (range) (range) and poorer baseline zinc status, although this deserves more thorough investigation using correlation and sensitivity analysis.Outcome Measures: SNAP 97.6 72.6 -24.3 <0.001 •The results observed cannot be directly attributed to the use of the nutrients without use of a control or placebo group. GivenEfficacy (scale range 0-270) (54-130) (48-107) (1- -43) the poor correlation with nutrient status, results should be interpreted with caution until expectation effects can be accounted •SNAP-IV parent rating scales. Validated psychometric scale based on DMS-IV diagnostic criteria for ADHD (90 items; scale: for. 0-3). (Baseline and 10 weeks). Serum Zn 10.9 11.1 0.8 0.014 Overall, it appears possible to design and evaluate a compound natural health product for this study based on existing •Connors 3 Parent. Validated psychometric scale based on population-based scores on DMS-IV diagnostic criteria for ADHD literature and guidelines for diagnosis and assessment of ADHD. (8.7 – 19.1 ug/L) (8.3 – 15.4) (8.8 – 15.8) (-0.1– 4.4) (108 items; scale 0-3. Scoring is based on clinically significant T score >72). (Baseline and 10 weeks). 4. Bilici, M et al. Double-blind, placebo-controlled study of zinc ReferencesSafety: Visual analogue scales and incidence of adverse events. RBC Mg 2.2 2.2 0.1 0.046 1. Wilens TE. Pharmacotherapy of adult attention deficit/hyperactivity disorder: a review. J sulphate in the treatment of attention deficit disorder. Prog Clin Psychopharmacol. 1995; 15(4):270-9 Neuropsychopharmacol Biol Psychiatry. 2004; 28(1):181-90Compliance: (1.7-2.7 mmol/L) (1.8-2.9) (1.8-2.8) (-0.2 - 0.5) 2. Chan E et al. Complementary and alternative therapies in childhood attention and 5. Konofal E et al. Iron deficiency in children with attention- hyperactivity problems. J Dev Behav Pediatr. 2003; 24(1):4-8 •Pill count (Baseline, 5 week and 10 weeks) 3. Mousain-Bosc M. Improvement of neurobehavioural disorders in children supplemented deficit/hyperactivity disorder. Arch Pediatr Adolesc Med. 2004; with magnesium-vitamin B6. Mag Res. 2006. 19(1):46-52 158(12):1113-5 •Food frequency questionnaire (FFQ) used pre- and post- to assess for major changes in diet. • Although mean change on the parent-rated SNAP were statistically significant, the range of improvements was broad. 13 The authors declare no conflict of interest SISU Inc. has had noBlood nutrient levels: •Erythrocyte (RBC) magnesium and zinc levels used to assess pre- and post- nutritional status. RBC levels are best long- participants (62%) were considered to be ‘responsive to treatment’ (>25% improvement on SNAP questionnaire). Conflict of Interest involvement in the design and conduct of the study. Study findings are not bound by any non-disclosure clauses. term indicator of nutritional status; ~7 weeks to notice significant change in zinc and magnesium levels. • Statistically significant improvements in Zn and Mg suggest that these outcome measures can change over the course of 10 Acknowledgements: Statistical Analysis weeks using the study product. Those participants taking the highest dose (5-6 pills/day) had a trend for larger, positive change in The authors wish to thank the Canadian Association for Attention Deficit Disorder Resource •The student’s t-test (2-tailed) was used to compared baseline and week 10 scores for efficacy. nutritional markers Alliance and the Child, Youth and Family Services department of CAMH for their assistance in recruitment. • The correlation co-efficient (r) was calculated to examine relationship between efficacy and each of the nutrients at baseline • The proportion of ‘responders’ to ‘non-responders’ did not differ amongst those who had low, medium or high changes in Zn or Funding: SISU Inc. has provided financial support and investigational product for this study. SISU and at 10 weeks (where appropriate). Mg. A low correlation was observed between changes in SNAP-IV and Zn (r=-0.059) and Mg (r=-0.202) Inc. has had no involvement in the design and conduct of the study. •All statistical analysis was done using Stats Direct version 2.7.7. KC was supported by SickKids Foundation Award for graduate studies in Clinical Trial Registration: NCT00704990 Complementary/Alternative Health Care during conduct of the study
  • 16. Methods of clinical teaching in a naturopathic teaching clinic – An exploratory observational study Nicole Henry1 ND, Kieran Cooley1 ND MSc 1 The Canadian College of Naturopathic Medicine Background Results• Medical education is continuously evolving, including ongoing development Table 2. Themesand change in both theoretical and practical teaching methods in the clinical Theme Example Participant Quotearena of naturopathic medical schools. A. Supervisor questions intern for understanding of illness “In terms of TCM (Traditional Chinese Medicine), were you able to come up with anything for her?” – Following a case presentation• There is a paucity of literature describing or evaluating the various styles ofclinical teaching of naturopathic educators, although there is some sense that where intern indicates that a TCM approach was being considered.these might mimic styles that are describing those of conventional medicine. B. Supervisor questions intern for rationale of proposed therapy “Was there a difference in cognition, was there better energy? … Do we know what her original B12 is?” – Following an intern’s• A description of current teaching styles will allow for an assessment of question about the frequency of administering intramuscular B12 injections.strengths and limitations as well as generate discussion in how best to D. Supervisor uses patient cases as a learning tool “Good. Well, I think its important to… get a baseline, especially if she hasn’t had one done in a little while… its one of those thingsevaluate and improve future clinical education. that can be insidious… So that’s exactly what I was hoping you would say – those screening exams and making sure they are all done or that you have a copy of them so that you have a baseline and you can make sure that nothing has been overlooked in that sense.” – Following a discussion regarding a patient who is generally healthy, outlining what may be done in such a case. Methodology• One researcher (NH) conducted semi-structured interviews and field E. Supervisor creates safe environment for intern to answer questions, “If you see an opportunity that you want to run with, whether it’s a team or group you are involved with, or an individual that youobservations from a random sampling of four naturopathic doctors take risks know that would want your services in some way, shape or form, and you want me to help you through that process, just ask, and(supervisors) in a naturopathic teaching clinic. we’ll make it happen. That’s why I’m here.”• Each supervisor was shadowed and tape-recorded for two 6-hour shifts I. Supervisors encourage and develop clinical reasoning skills in the “What is she doing that’s causing these problems? Running, biking, nothing? Because you don’t get tendonopathies from doing interns yoga…Nothing that is HLAB27 positive? No rheumatic issues that we know of? No psoriatic arthritis, nothing like that?”where they were overseeing education and patient care provided by 6-7 internsin their final year of a 4-year naturopathic medical diploma program. Figure 1: Frequency and Distribution of Educational Themes for each supervisor• A ½ to 1-hour tape-recorded semi-structured interview took place with each (a) I Discussionof the four participants. A grounded theory exploration of medical teaching In (a) the overall frequency of the top 5 • Overall, supervisors varied in their approach to teaching and the microskills Thematic Code E S04literature 1,2 provided a background framework for design of the semi- D S03 codes of an entire shift is outlined per employed, some more balanced than others, with an apparent emphasis on providing a S02structured interview questions. B S01 supervisor; in (b) the distribution of all safe environment where interns could answer questions and take risks. Least codes over a shift is divided by patient emphasized was prompting for rationale of proposed therapy.• Transcripts of tape-recordings and field notes were used to generate Athemes. Independent analysis was conducted by two researchers to generate visits and preview/review. • Virtually all relied heavily on their previous experience when instructing interns. 0 5 10 15 20initial themes. Following this, iterative content analysis and discussion was Frequency • As compared to preview and review, more modeling and intervention in patientused to reach consensus. management and care occurred during patient visits. (b) 20 7• Ethical approval and oversight of this study was sought and obtained from 18 S01 6 S02 • Supervisors provide feedback, though rarely labeled as such and often non-specific. 16the research ethics board of the Canadian College of Naturopathic Medicine. 14 5 • Based on the literature, supervisors in a naturopathic medical teaching clinic employ Incidence IncidenceAll participants provided free and informed consent prior to volunteering for 12 10 4 similar methods to those in conventional medical teaching clinics. Pt visits 3 Pt visitsthe study. 8 6 Prev/rev Prev/rev • Future studies may include interviewing interns to compare and contrast the 2 4 1 perspectives of interns and supervisors, and comparing teaching methods across the 2Table 1. Participant Characteristics 0 0 clinical internship (e.g. at start and end). a b c d e f g h I j k l m n o p q r a b c d e f g h I j k l m n o p q r Practice type 3 Urban, 1 Rural Thematic codes Thematic codes Gender Females: 2, Males: 2 References 14 S03 7 S04 Practice 1. Hartley S et al Teaching in the Clinical Setting. In: Teaching Medical Students in Primary and Secondary Range from 5-18 years 12 6 experience 10 5 Care: A Resource Book. USA: Oxford University Press, 2003. p.111-132 Incidence Incidence 8 4# yrs at teaching 3 4 3 3 2. Irby DM. Effective Clinical Teaching & Learning : Clinical Teaching and the Clinical Teacher. [Online]. 6 Pt visits 3 Pt visits clinic Prev/rev Prev/rev 4 2 Most common MSK, Sport Gastrointestinal Women’s Women’s 2 1 Acknowledgmentspatient population health, health, 0 0 • The authors wish to graciously thank all study participants, Kimberlee Blyden-Taylor and the a b c d e f g h I j k l m n o p q r a b c d e f g h I j k l m n o p q r pediatrics endocrine Canadian College of Naturopathic Medicine for their assistance and contribution to the conduct Thematic codes Thematic codes of this project.
  • 17. Integrative Medicine: Exploring the barriers to effective communication between family physicians and naturopathic doctors Chris Pickrell ND1, Matt Chellew BSc MD2, Dugald Seely BSc ND MSc1, Kieran Cooley1 ND MSc 1 The Canadian College of Naturopathic Medicine 2 North York General Hospital General Background Results• The high use of complementary/alternative services and therapies (CAM) Table 2. Themes & participant quotes from MDs and NDsalongside a movement towards providing integrative patient-centred care for Theme Example Participant QuoteCanadians suggests a demand for effective communication between CAM and‘conventional’ health care practitioners. “They provide a fee-for service care to help prevent disease and optimize health using natural means.” General understanding “They triage, fill a role as gatekeeper, refer, and quickly assess and treat disease.” “Patients mostly complain to us for instance that their doctor just doesn’t• Some theoretical understanding regarding the need for improved listen to them, doesn’t hear them, doesn’t have time for them, and tend to write [their health concerns] off as being minor issues.”communication surrounding integrative approaches to care exists, howeverthere is a paucity of literature describing practitioner-identified obstacles to Mixed. “[In Ontario], it’s a regulated profession, [but elsewhere] any turkey who read something on the Internet can call themselves a naturopath.”integration in a non-integrative setting. Experience working with the other “I’ve had a whole group [of patients]…where the naturopath’s done so much better than we could ever hope to do with our modern medical armamentarium.”• This study sought to explore barriers in communication between family profession Mixed. “They know that I exist and they’re not upset by it, but they’re…not necessarily working with me – they’re just sort of accepting my existence.” “I’vephysicians (MDs) from Toronto’s North York General Hospital (NYGH) and probably now mailed – and I’m not exaggerating – probably upwards of 500 letters in the last 10 years. I’ve maybe received 5 phone calls. One letter back.”naturopathic doctors (NDs) from the neighboring Canadian College of “My role is to make sure there isn’t a disaster coming…the naturopath’s role is to alter the way they live, alter the way they eat, alter the way they exercise…toNaturopathic Medicine (CCNM). Role in patient management make the patient better…the naturopath’s role is to fix them.”• A participatory action approach was taken to prompt study participants to “a family doctor is the starting point and gateway…they’re really the first point of contact for most patients, and to me they’re an essential service for our healthbegin initial steps at creating a tool to enhance communication. care system – we need more family doctors…” “I do notice sometimes, that there’s still resistance from both sides, because there are misconceptions…as to what the other side is doing.” Methodology Lack of practical knowledge Through lack of exposure, potential for inaccurate practical understanding of the scope of practice and training held by a naturopathic doctor• Two researchers (CP and MC) conducted semi-structured interviews with “Either you don’t do it [labwork] or if you do do it, make sure you’ve got the resources to manage it on your side…don’t send me anything that adds to myvolunteer participants from NYGH and CCNM. Participants were recruited workload, because there’s just not enough family doctors…[if] I have to follow it up, it affects my access, it affects my efficiency…it’s bad for patients…[and] Lack of time for communicationusing email and poster advertisements at both locations. it’s a good way to piss off your family doctors.” “What I used to do is just write a clinical note to the doctor. And honestly, I think that’s a good (emphasized) idea because I think that the doctors appreciate• Transcripts of tape-recorded interviews were used for interpretive it. But to be honest with you, I just don’t have time to do it, and that’s the reason that I don’t do it anymore.”content analysis of themes. An iterative interviewing-analysis approach There is no standard or accepted method of efficient and effective communication between the groups. Change needs to happen from the ‘top down’ towas used to enrich expression of themes. facilitate a shared tool or means for helping us bridge the communication gap. Health care system ‘barriers’• Recruitment continued in both MD and ND groups until saturation of “I think each professional organization needs to make it almost one of their policies or mandates that you really need to collaborate…you need to basically workthemes was reached. alongside other health care providers – including medical doctors, including naturopathic doctors – when needed.”• The Research Ethics Boards of both NYGH and CCNM provided ethical “Yes [there is a need to improve communication] but the fact is, there is no communication right? I don’t know what you do, you don’t know what I do, we all run around with our preconceived notions, all live in our silos, and the patient gets caught in the middle, and that’s no good for anybody.”review and oversight of the project. “You need to have a look at your [ND] process…you need to think about how you communicate with us, what you bring of value, and how often you want to Communication send us letters and what we’re going to do to send people to you.” Table 1. Participant Characteristics “…we’re not working in opposition with them [FPs], and they need to know that working together can relieve some of the burden…and still maintain the MD ND integrity of their profession…” Age 52 ±5.1 40 ±9.1 Discussion References 1. Caspi O, Bell IR, Rychener D et al. The Tower of Babel: Communication and Years in practice 25 ±6.1 7 ±2.5 Three main barriers were identified: 1) the importance of recognizing the strength and limitations of Medicine: An Essay on Medical Education and Complementary-Alternative professional roles in the larger health care system, 2) the need to develop a personal or professional Medicine. Arch Intern Med 2000; 160: 3193-3195. Visits/month 361 ±122.7 144 ±33.9 relationship as key to confident communication, and 3) the need for collaborative education as the 2. Frenkel MA, Borkan JM. An approach for integrating complimentary- foundation for establishing good communication and professional association. alternative medicine into primary care. Family Practice 2003; 20: 324-332 % with multidisciplinary 50% 50% While all agreed that communication needs to improve for the betterment of patient-centered care and practice setting health care system improvements, efforts around interprofessional education would only surmount Acknowledgments some of the barriers that were identified. A structured process (medical letter writing akin to the The authors wish to graciously thank all study participants, and % of patients incorporating 14.5% 100% system of communication between family physicians and specialists) or shared communication the residency programs of NYGH and CCNM for their assistance other’s system of care through electronic medical records may be ideal, if the health care system could accommodate this and contribution to the conduct of this project. initiative.
  • 18. An N-of-1 Placebo-Controlled Trial in Clinical Practice: Testing the Effectiveness of Oral Niacinamide (Nicotinamide) for the Treatment of Anxiety Jonathan E. Prousky, ND, MSc1,2 1Chief Naturopathic Medical Officer, Professor, Canadian College of Naturopathic Medicine 2Editor, Journal of Orthomolecular Medicine Background ResultsAnxiety disorders are the most common psychiatric disorders Figure 1: BAI Results Over Time Figure 2 shows a trend toward the placebo having an effectin the United States, affecting 18% of adults (about 40 over the niacinamide. There was no statistically significantmillion) age 18 years and older in a given year. In Canada, 40 difference in the BAI results from the niacinamide and12% of the entire adult population (15-64 years of age) has 30 30 placebo treatments (p=0.0746) over the entire study period. BAI Scorean anxiety disorder, with 9% of men and 16% of women BAI Results Overbeing diagnosed during a one-year period. A significant 20 Time There were no statistically significant differences between 15 14amount of patients having anxiety turn to complementary and 10 13 the niacinamide and placebo treatments for all the 7alternative medical (CAM) treatments. 3 0 dimensions of the MYMOP, which include Symptoms 1 (selfAn emerging CAM treatment that shows potential as an 2 4 6 8 10 12 confidence) and 2 (concentration), Activity (examanxiolytic agent is the amide form of vitamin B-3, also known Weeks preparation), and Wellbeing over the duration of the niacinamide (nicotinamide). Niacinamide is readily During weeks 1 and 2, the participant was in the washout cycle Thus, there were no statistically significant differencesavailable over-the-counter in most drugstores and health of the trial. During weeks 3 and 4, the participant was taking observed in Symptom 1 (p=0.30), Symptom 2 (p=0.40),food stores. The use of large pharmacological doses (≥ 1500 placebo and the BAI score at the end of the 2-weeks declined. Activity (p=0.13), and Wellbeing (p=0.09).mg/day) of niacinamide has been shown in several published During weeks 5 and 6, the participant was taking niacinamidecase reports to improve symptoms of anxiety. and the BAI score slightly increased. During weeks 7 and 8, the As shown in Figure 3, there were no statistically significant participant was in the final washout cycle of the trial, and the differences observed in the AST (p=0.39) and ALT (p=0.62) BAI score was 14. Between weeks 9 and 10, the participant values as a consequence of either niacinamide or placebo. Methodology was taking placebo and the BAI score declined once again. Figure 3: Transaminase ResultsThis N of 1 trial (14-week study) commenced in February Between weeks 11 and 12, the participant was taking niacinamide and the BAI score increased. 302008 and ended in May 2008, and involved one participant. 25 23 24 22Following a 2-week washout cycle, the 26-year-old female Figure 2: Changes in BAI Over Time 20 21 20 20 19 17 16 AST U /Lparticipant was allocated to a 4-week treatment Period (Block) 15 10 ALTwhere she was provided with 3000 mg/day of niacinamide, or 10an equivalent-looking placebo, at 2-week intervals. Following 4 0another 2-week washout cycle, the same procedure was 5 2 2 4 6 8 10 12 Change in BAIfollowed. Main outcome measures included: Beck Anxiety 0 WeeksInventory (BAI) questionnaire; Measure Yourself Medical PlaceboOutcome Profile (MYMOP) questionnaire; 14-day medication -5 Niacinamide Conclusiondiary for side effects and pill counts; and laboratory testing to Treatment with niacinamide produced no favourable therapeutic -10monitor safety and possible toxicity. effects upon the participant’s symptoms of anxiety and main outcome -11 measures. There was, however, a consistent improvement in the -15Figure 1 demonstrates a continuous decline over time in the participant’s anxiety and main outcome measures over time. TheBAI results. -17 participant in this trial improved as a result of simply being treated. -20 Niacinamide was safe at dosages as high as 3000 mg/day. Weeks
  • 19. Randomized, double-blind, placebo-controlled pilot trial assessing the ability of inositol hexaniacinate (hexanicotinate) to reduce symptoms of nonulcer dyspepsia possibly due to insufficient hydrochloric acid production Jonathan E. Prousky, ND, MSc1, and Dugald Seely, MSc, ND2 1Chief Naturopathic Medical Officer, Professor, Canadian College of Naturopathic Medicine; Editor, Journal of Orthomolecular Medicine Medicine 2Director of Research, Canadian College of Naturopathic Medicine; Editor, International Journal of Naturopathic Medicine Randomization was facilitated by a computer generated list There was a highly significant decrease (p<0.01) in fasting Background with each subject assigned to the intervention or placebo group gastric pH levels (independent of the intervention) in the in a blinded fashion by the trial coordinator (Seely) according to second visit over the first visit in both placebo and treatmentDyspepsia is defined as chronic or recurrent discomfort the allocation list. Eleven subjects in total were assigned to theconcentrated in the upper abdomen and associated with intervention group and 11 subjects were assigned to the groups (Figure 2).belching, bloating, heartburn, nausea, and vomiting. It affects placebo group. The average age (years) of the subjects in theapproximately twenty-five percent of the population each intervention group was 25.55 ± 3.38 and in the placebo group Figure 2. Alterations of Fasting Gastric pH Levelyear. Fifty to sixty percent of patients with dyspepsia have was 26.91 ± 3.45. There were 10 females and 1 male in thefunctional or nonulcer dyspepsia (NUD) where no specific intervention group and 9 females and 2 males in the placebo 10aetiology can be identified. group. Twenty-two subjects returned after the 30 days to redo 9 8 the Gastro-Test®. Each subject was also asked to completeProusky and Seely reported some evidence of a therapeutic the Gastrointestinal Symptom Questionnaire at baseline and 7 pH Level 6effect in which a patient was given inositol following 30 days of treatment with either IHN or placebo. Intervention 5hexaniacinate/hexanicotinate (IHN), a specific form of Subjects were also asked to complete a medication diary and 4 Placebovitamin B-3. IHN appeared to lower fasting gastric pH, i.e., return any remaining pills at the time of their second Gastro- 3increased gastric hydrochloric acid (HCl) secretion, and Test® for pill count. None of the subjects were taking 2reduce symptoms of achlorhydria. It was hypothesized that prescription medication for dyspepsia. 1IHN might have reduced symptoms of NUD by facilitating 0gastric HCl secretion. Results Before AfterTo evaluate whether IHN has the ability to reduce symptoms There was a non-significant (i.e., non-statistical) trend towards aof NUD, we conducted a randomized, placebo-controlled trial There was no significant correlation between fasting gastric total Gastrointestinal Symptom Questionnaire score decrease in pH levels and the total Gastrointestinal Symptomto test this hypothesis. Herein we describe a trial on subjects the treatment group compared to the control group, as Questionnaire scores among the 62 subjects that werewith insufficient fasting gastric HCl production, as determinedby Gastro-Test® pH measurements above 3. The results of evaluated by a random effect model (p = 0.08, Figure 1). evaluated (r = -0.1142, p = 0.33). We were expecting to see athis study should help elucidate whether IHN can effectively correlation between total Gastrointestinal Symptomreduce symptoms of NUD and/or stimulate fasting gastric Figure 1. Alterations of Total Gastrointestinal Symptom Questionnaire Score Questionnaire scores and fasting gastric pH measurements,HCl secretion. in that, high questionnaire scores would correlate with higher (i.e., basic) fasting gastric pH measurements Methodology 18 16 14 ConclusionSixty-two subjects attended the trial commencement dates Total Score 12(36 on October 17, 2003 and 26 on October 21, 2004), and 10 Intervention There was a non-significant trend towards symptomaticwere administered the Gastro-Test® according to the 8 improvement among participants taking IHN compared to those Placebopublished procedure between the hours of 8:00AM and 6 on placebo. IHN might be a promising treatment for NUD, but9:00AM. Each subject also completed the GastrointestinalSymptom Questionnaire. The questionnaire, developed by 4 further investigation is required. The total Gastrointestinal 2Prousky, identifies 15 symptoms that reflect insufficient 0 Symptom Questionnaire score did not correlate with gastric pHHCl production, and assesses their presence and Before After as measured by the Gastro-Test®. This finding was potentiallyfrequency on a 3-point (0-3) Likert-type scale. the result of operator inexperience with the Gastro-Test® procedure.