title: Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a protocol for a systematic review and network meta-analysis of primary prevention trials.
abstract: BACKGROUND
  In the Western world, dietary supplements are commonly used to prevent chronic diseases, mainly cardiovascular disease and cancer. However, there is inconsistent evidence on which dietary supplements actually lower risk of chronic disease, and some may even increase risk. We aim to evaluate the comparative safety and/or effectiveness of dietary supplements for the prevention of mortality (all-cause, cardiovascular, and cancer) and cardiovascular and cancer incidence in primary prevention trials.
  
  
  METHODS
  We will search PubMed, EMBASE, Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled Trials, clinical trials.gov, and the World Health Organization International Trial Registry Platform. Randomized controlled trials will be included if they meet the following criteria: (1) minimum intervention period of 12 months; (2) primary prevention of chronic disease (is concerned with preventing the onset of diseases and conditions); (3) minimum mean age ≥18 years (maximum mean age 70 years); (4) intervention(s) include vitamins (beta-carotene, vitamin A, B vitamins, Vitamin C, Vitamin D, Vitamin E, and multivitamin supplements); fatty acids (omega-3 fatty acids, omega-6 fatty acids, monounsaturated fat); minerals (magnesium, calcium, selenium, potassium, iron, zinc, copper, iodine; multiminerals); supplements containing combinations of both vitamins and minerals; protein (amino acids); fiber; prebiotics; probiotics; synbiotics; (5) supplements are orally administered as liquids, pills, capsules, tablets, drops, ampoules, or powder; (6) report results on all-cause mortality (primary outcome) and/or mortality from cardiovascular disease or cancer, cardiovascular and/or cancer incidence (secondary outcomes). Pooled effects across studies will be calculated using Bayesian random effects network meta-analysis. Sensitivity analysis will be performed for trials lasting ≥5 years, trials with low risk of bias, trials in elderly people (≥65 years), ethnicity, geographical region, and trials in men and women. The results of the corresponding fixed effects models will also be compared in sensitivity analyses.
  
  
  CONCLUSIONS
  This is a presentation of the study protocol only. Results and conclusions are pending completion of this study. Our systematic review will be of great value to consumers of supplements, healthcare providers, and policy-makers, regarding the use of dietary supplements.
  
  
  BACKGROUND
  
  CRD42014014801 .
authors: Department of Nutritional Sciences, Faculty of Life Sciences, University of Vienna, Althanstraße 14 (UZA II),, 1090, Vienna, Austria. lukas.schwingshackl@univie.ac.at.|German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany. lukas.schwingshackl@univie.ac.at.
authors: Lukas
authors: L
authors: Schwingshackl
authors: Department of Nutritional Sciences, Faculty of Life Sciences, University of Vienna, Althanstraße 14 (UZA II),, 1090, Vienna, Austria. georg.hoffmann@univie.ac.at.
authors: Georg
authors: G
authors: Hoffmann
authors: German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany. Brian.Buijsse@dife.de.
authors: Brian
authors: B
authors: Buijsse
authors: German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany. Tamara.Mittag@dife.de.
authors: Tamara
authors: T
authors: Mittag
authors: German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany. Marta.Stelmach@dife.de.|Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland. Marta.Stelmach@dife.de.
authors: Marta
authors: M
authors: Stelmach-Mardas
authors: German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany. boeing@dife.de.
authors: Heiner
authors: H
authors: Boeing
authors: German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany. Marion.Gottschald@dife.de.
authors: Marion
authors: M
authors: Gottschald
authors: German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany. Stefan.Dietrich@dife.de.
authors: Stefan
authors: S
authors: Dietrich
authors: German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany. maria.arregui@dife.de.
authors: Maria
authors: M
authors: Arregui
authors: School of Social and Community Medicine, University of Bristol, Canynge Hall 39, Whatley Road, BS8 2PS, Bristol, UK. S.Dias@bristol.ac.uk.
authors: Sofia
authors: S
authors: Dias
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality; D002423:Cause of Death; D002985:Clinical Protocols; D004043:Dietary Fiber / Q000008:administration & dosage; D019587:Dietary Supplements / Q000009:adverse effects*; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage; D006801:Humans; D018977:Micronutrients / Q000008:administration & dosage; D009369:Neoplasms / Q000209:etiology / Q000401:mortality; D012107:Research Design; D000078202:Systematic Reviews as Topic
chemical_list: D000596:Amino Acids; D004043:Dietary Fiber; D005231:Fatty Acids, Unsaturated; D018977:Micronutrients