Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies

Authors: HARRIS, WILLIAM - University Of South Dakota; TINTLE, NATHAN - Dordt College; IMAMURA, FUMIAKI - University Of Cambridge; MARKLUND, MATTI - University Of New South Wales; DJOUSSE, LUC - Brigham & Women'S Hospital; BASSETT, JULIE - Cancer Council Victoria; CARMICHAEL, PIERRE - Quebec Center Of Excellence On Aging; CHEN, YUN - National Taiwan University; HIRAKAWA, YOICHIRO - Kyushu University; KÜPERS, LEANNE - Wageningen University; LAGUZZI, FREDERICA - Karolinska Institute; LANKINEN, MARIA - University Of Eastern Finland; MURPHY, RACHEL - University Of British Columbia; SAMIERI, CÉCILIA - University Of Bordeaux; SENN, MACKENZIE - Children'S Nutrition Research Center (CNRC); SHI, PEILIN - Friedman School At Tufts; VIRTANEN, JYRKI - University Of Eastern Finland; BROUWER, INGEBORG - Vrije University; CHIEN, KUO - National Taiwan University; EIRIKSDOTTIR, GUDNY - Icelandic Heart Association; FOROUHI, NITA - University Of Cambridge; GELEIJNSE, JOHANNA - Wageningen University; GILES, GRAHAM - University Of Melbourne; GUDNASON, VILMUNDUR - University Of Iceland; HELMER, CATHERINE - University Of Bordeaux; HODGE, ALLISON - University Of Melbourne; JACKSON, REBECCA - The Ohio State University; KHAW, KAY - University Of Cambridge; LAAKSO, MARKKU - University Of Eastern Finland; LAI, HEIDI - Friedman School At Tufts; LAURIN, DANIELLE - Quebec Center Of Excellence On Aging; LEANDER, KAREN - Karolinska Institute; LINDSAY, JOAN - University Of Ottawa; MICHA, RENATA - Friedman School At Tufts; MURSO, JAAKO - University Of Eastern Finland; NINOMIYA, TOSHIHARU - Kyushu University; POST, WENDY - Johns Hopkins School Of Public Health; PSATY, BRUCE - University Of Washington; RISÉRUS, ULF - Uppsala University; ROBINSON, JENNIFER - University Of Iowa; SHADYAB, ALADDIN - University Of California, San Diego; SNETSELAAR, LINDA - University Of Iowa; SALA-VILA, ALEIX - Barcelonabeta Brain Research Center; SUN, YANGBO - University Of Iowa; STEFFAN, LYN - University Of Minnesota; TSAI, MICHAEL - University Of Minnesota; WAREHAM, NICK - University Of Cambridge; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); WU, JASON - University Of New South Wales; QIAN, FRANK - Harvard School Of Public Health; ARDISSON KORAT, ANDRES - Brigham & Women'S Hospital; SISCOVICK, DAVID - New York Academy Of Medicine; LEMAITRE, ROZENN - University Of Washington; MOZAFFARIAN, DARIUSH - Friedman School At Tufts

Submitted to: Nature Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/12/2021
Publication Date: 4/22/2021
Citation: Harris, W.S., Tintle, N.L., Imamura, F., Marklund, M., Djousse, L., Bassett, J.K., Carmichael, P.H., Chen, Y.Y., Hirakawa, Y., Kupers, L.K., Laguzzi, F., Lankinen, M., Murphy, R.A., Samieri, C., Senn, M.K., Shi, P., Virtanen, J.K., Brouwer, I.A., Chien, K.L., Eiriksdottir, G., Forouhi, N.G., Geleijnse, J.M., Giles, G.G., Gudnason, V., Helmer, C., Hodge, A., Jackson, R., Khaw, K.T., Laakso, M., Lai, H., Laurin, D., Leander, K., Lindsay, J., Micha, R., Murso, J., Ninomiya, T., Post, W., Psaty, B.M., Riserus, U., Robinson, J.G., Shadyab, A.H., Snetselaar, L., Sala-Vila, A., Sun, Y., Steffan, L.M., Tsai, M.Y., Wareham, N., Wood, A.C., Wu, J.H., Qian, F., Ardisson Korat, A.V., Siscovick, D.S., Lemaitre, R.N., Mozaffarian, D. 2021. Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies. Nature Communications. 12:2329. https://doi.org/10.1038/s41467-021-22370-2.
DOI: https://doi.org/10.1038/s41467-021-22370-2

Interpretive Summary: The health effects of omega-3 fatty acids (n-3 FAs) in the diet are highly controversial; although many observational studies show an association with adverse cardiovascular events these are not robustly supported by intervention studies which supplement the diet with n-3 FAs. In addition, studies have yet to see whether a high intake of n-3 FAs is associated with later mortality. To investigate this, we combined data from 17 studies which measured the level of n-3 FAs in the blood at the beginning of the study, and followed individuals recording death rates over time. When looking over approximately 15 years, risk for death from all causes was significantly lower in those who with the highest levels of n-3 FAs vs. those who with the lowest (highest vs. the lowest quintile). However, further investigation found that this finding was specific to the type of n-3 FA studied. These novel findings suggest that higher circulating levels of specific marine n-3 FAs may be associated with a lower risk of premature death, which may help inform future dietary guidelines at the population level.

Technical Abstract: The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15–18%, at least p<0.003) in the highest vs the lowest quintile for circulating long chain (20–22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.