Vitamin D and Fish Oil for Autoimmune Disease, Inflammation and Joint Pain
Principal Investigator: Karen H Costenbader
Abstract: DESCRIPTION (provided by applicant): - We propose to leverage a newly NIH-funded large, randomized, double-blind, placebo-controlled, 2x2 factorial trial of vitamin D (in the form of vitamin D3 [cholecalciferol]) and marine omega-3 fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements to study effects upon autoimmune disease incidence, biomarkers of systemic inflammation, and chronic knee pain. Data from laboratory studies, epidemiologic research, and small prevention trials strongly suggest that these nutritional agents reduce the risk of autoimmune diseases, reduce levels of circulating pro-inflammatory cytokines, and decrease chronic joint pain. However, large primary prevention trials with adequate dosing in general populations (i.e., unselected for disease risk) have never been conducted. The growing enthusiasm for supplemental vitamin D and fish oils underscores the urgent need for their timely testing, before their use becomes so prevalent as to render participant recruitment and hypothesis testing impossible. The NIH-funded VITAL randomized controlled trial about to begin will involve 20,000 men aged e60 and women aged e65 recruited from a mailing to 1.2 million persons, including members of AARP (formerly known as the American Association of Retired Persons), and others. The mailing will contain a letter describing the trial, an informed consent form, and a questionnaire about past medical history, including autoimmune diseases and a screening assessment of chronic knee pain, as well as diet, medication and nutritional supplement use. At the end of a 3 month placebo run-in, those who remain willing and eligible, and who report having taken at least two-thirds of the pills, will be randomly assigned to one of four treatment groups for 5 years: vitamin D3 (1600 IU/d) and fish oil (EPA+DHA, 1 g/d);vitamin D3 and fish oil placebo;placebo vitamin D3 and fish oil;and placebo vitamin D3 and placebo fish oil. At yearly intervals, participants will receive a new supply of pills, and assessments of incident autoimmune diseases, knee pain, compliance and potential side effects. A physician endpoints committee will confirm all autoimmune disease endpoints by medical record review. We anticipate validation of 600 incident cases of autoimmune disease, giving us sufficient statistical power to assess supplement effects on disease incidence. Blood samples at baseline and in follow-up will be collected in a random subcohort of 2000 individuals and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein, interleukin-6, and tumor necrosis factor-a. Approximately 2000 individuals with chronic, frequent knee pain will be followed with annual questionnaires, providing ample statistical power to evaluate the supplement effects upon chronic knee pain. To complete the pre-randomization assessment of knee pain, it is critically important that this ancillary study be undertaken in parallel to enrollment for the parent VITAL trial, beginning January 2010. Given the NIH-funded VITAL trial and our success with prior large mail-based trials and cohort studies, the proposed trial will furnish either definitive positive or informative null results regarding the central study hypotheses. PUBLIC HEALTH RELEVANCE: The purported health benefits of vitamin D and marine omega-3 fatty acids for preventing autoimmune diseases, decreasing inflammation and relieving joint pain are receiving increasing attention in the medical literature and the popular press. However, definitive data supporting these health benefits of these two readily available over-the-counter agents are lacking. Findings from this large randomized clinical trial will clarify the roles of vitamin D and marine omega-3 fatty acid supplements for the prevention of autoimmune diseases, effects on levels of biomarkers of systemic inflammation, and treatment for chronic knee pain in older men and women.
Funding Period: 2010-05-07 - 2015-04-30
more information: NIH RePORT
- Does vitamin D affect risk of developing autoimmune disease?: a systematic reviewMartin A Kriegel
Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA
Semin Arthritis Rheum 40:512-531.e8. 2011..We evaluated the epidemiologic evidence that vitamin D may be related to human autoimmune disease risk...
- The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular diseaseJoAnn E Manson
Division of Preventive Medicine, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 900 Commonwealth Avenue East, Boston, MA 02215, United States
Contemp Clin Trials 33:159-71. 2012....
- Effect of Vitamin D and Omega-3 Fatty Acids on Blood Pressure and HypertensionHoward D Sesso; Fiscal Year: 2013..Because high blood pressure is responsible for one out of every six deaths in the United States, the results of this study could possibly improve the health of many people. ..
- The VITAL Rhythm StudyChristine M Albert; Fiscal Year: 2013..If either agent significantly lowers AF risk, then these agents would represent one of the first therapies proven effective for the primary prevention of this growing morbid disease. ..
- Vitamin D Effect on Body Composition During Behavioral Weight Loss in WomenANNE M MCTIERNAN; Fiscal Year: 2013....
- Hopkins Center for Eliminate Cardiovascular Health DisparitiesLisa A Cooper; Fiscal Year: 2013..abstract_text> ..
- Comparative Mechanisms of Cancer ChemopreventionRoderick H Dashwood; Fiscal Year: 2013..This application is innovative and timely in bridging basic mechanisms, preclinical models, and human studies of epigenetics and diet. ..