Listed in Issue 277


MANSON and COLLEAGUES, VITAL Research Group: John Baron, Michael Holick, Bruce Hollis, Diane Gold, Meryl LeBoff, Olivia Okereke, Aruna Pradhan, Howard Sesso, Wendy Chen, Paulette Chandler, J Michael Gaziano, Olga Demler, Kathryn Rexrode, Karen Costenbader, John Forman, Erik Alexander, Sonia Friedman, Jeffrey Katz, Shumin Zhang, Jennifer Lin, Joseph Walter, Julie Duszlak, Kate Kalan, Jean MacFadyen, Natalya Gomelskaya, David Bates, Ara Sarkissian, Mary Breen, Yeulolani Andrade, Manickavasagar Vinayagamoorthy, Chunying Li, Eunjung Kim, Franco Giulianini, Gregory Kotler, Marty Van Denburgh, Rimma Dushkes, Yanyan Liu, Eduardo Pereira, Lisa Fields-Johnson, George Menjin, Lucy Liu, Lauren Girard, Scott Zeller, Naomi Riches, Katelyn Hasson, Ellen Bhang, Maria Revilla, Elena McCarthy, Alex Moran, Kristen Haise, Leah Arsenault, Philomena Quinn, Sancia Grimes, Ivan Fitchorov, Kurt Schwerin, Shamikhah Curry, Annie Murray, Angela Zhang, Diana Walrond-Williams, Alison Weinberg, Chris Pfeffer, Margarette Haubourg, Viviane Nguyen, Henry Ouellette, Rolando Rodriguez, Tony Montgomery, Keith Morse, Vincent Guzman, Megan Perry, Sandra Weekes, Doug Smith, Allison Clar, Sara Curran, Yaneve Fonge, David Hibbert, Louisa Paine, Kelly Royce, Courtney Splaine, Jennifer McMahon, David Eldridge, Laura Hand, Kay Inandan, Meghan Rieu Werden, Harriet Samuelson, Andrea Hrbek, Megan Mele, Eileen Bowes, Mary Anne Ryan, Carlos Camargo, Jacqueline Danik, Ravi Thadhani, Thomas Wang, Raj C Shah, Michelle A Albert, Carlos Kase, Hubert Vesper, Julianne Botelho, Nanette Wenger, Lawrence S Cohen, Theodore Colton, Mark A Espeland, Craig Henderson, Alice H Lichtenstein, Rebecca A Silliman, Josephine Boyington, Rebecca Costello, Cindy Davis, Peter Greenwald, Gabriela Riscuta, Harold Seifried, 1 From the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (J.E.M., N.R.C., I-M.L., W.C., S.S.B., S.M., H.G., C.M.A., D.G., T.C., D.D., G.F., C.R., V.B., E.L.G., W.C.W., J.E.B.), and the Departments of Epidemiology (J.E.M., N.R.C., I.-M.L., W.C.W., J.E.B.) and Nutrition (E.L.G., W.C.W.), Harvard T.H. Chan School of Public Health - all in Boston conducted a randomized, placebo-controlled trial of vitamin D3 and marine n-3 fatty acids for heart disease and cancer in men and women in the USA.


Higher intake of marine n-3 (also called omega-3) fatty acids has been associated with reduced risks of cardiovascular disease and cancer in several observational studies. Whether supplementation with n-3 fatty acids has such effects in general populations at usual risk for these end points is unclear.


We conducted a randomized, placebo-controlled trial, with a two-by-two factorial design, of vitamin D3 (at a dose of 2000 IU per day) and marine n-3 fatty acids (at a dose of 1 g per day) in the primary prevention of cardiovascular disease and cancer among men 50 years of age or older and women 55 years of age or older in the United States. Primary end points were major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes) and invasive cancer of any type. Secondary end points included individual components of the composite cardiovascular end point, the composite end point plus coronary revascularization (expanded composite of cardiovascular events), site-specific cancers, and death from cancer. Safety was also assessed. This article reports the results of the comparison of n-3 fatty acids with placebo.


A total of 25,871 participants, including 5106 black participants, underwent randomization. During a median follow-up of 5.3 years, a major cardiovascular event occurred in 386 participants in the n-3 group and in 419 in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P=0.24). Invasive cancer was diagnosed in 820 participants in the n-3 group and in 797 in the placebo group (hazard ratio, 1.03; 95% CI, 0.93 to 1.13; P=0.56). In the analyses of key secondary end points, the hazard ratios were as follows: for the expanded composite end point of cardiovascular events, 0.93 (95% CI, 0.82 to 1.04); for total myocardial infarction, 0.72 (95% CI, 0.59 to 0.90); for total stroke, 1.04 (95% CI, 0.83 to 1.31); for death from cardiovascular causes, 0.96 (95% CI, 0.76 to 1.21); and for death from cancer (341 deaths from cancer), 0.97 (95% CI, 0.79 to 1.20). In the analysis of death from any cause (978 deaths overall), the hazard ratio was 1.02 (95% CI, 0.90 to 1.15). No excess risks of bleeding or other serious adverse events were observed.


Supplementation with n-3 fatty acids did not result in a lower incidence of major cardiovascular events or cancer than placebo. (Funded by the National Institutes of Health and others; VITAL number, NCT01169259 .).


JoAnn E Manson  1 , Nancy R Cook  1 , I-Min Lee  1 , William Christen  1 , Shari S Bassuk  1 , Samia Mora  1 , Heike Gibson  1 , Christine M Albert  1 , David Gordon  1 , Trisha Copeland  1 , Denise D'Agostino  1 , Georgina Friedenberg  1 , Claire Ridge  1 , Vadim Bubes  1 , Edward L Giovannucci  1 , Walter C Willett  1 , Julie E Buring  1 , VITAL Research Group

Collaborators. Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer

N Engl J Med; 380(1):23-32. Jan 3 2019. doi: 10.1056/NEJMoa1811403. Epub Nov 10 2018 .

ICAN 2024 Skyscraper

Scientific and Medical Network 2

Cycle Around the World for Charity 2023

Climb Mount Kilimanjaro Charity 2023

top of the page