Diet and Longevity Research

I grew sick dealing with contradictory and unsubstantiated diet advice. This page is a compilation of scientific papers that study how diet changes affect mortality.

Actionable Advice

The two pieces of advice that I'm most confident in are

  1. Eat more polyunsaturated fats, especially omega-3.
  2. Take vitamin D supplements.

Unfortunately many of the studies I found involve changing people's polyunsaturated fat intakes, which makes it hard to determine what else matters. Based on the studies I've found, the only other statement I'm at all confident endorsing is that at of vegetables, fruits, and grains, at least one reduces mortality.

RCT Meta-Analyses

  • "Reducing saturated fat by reducing and/or modifying dietary fat reduced the risk of cardiovascular events by between 4% and 23% but had no effect on overall or cardiac mortality Sills.
  • Increasing polyunsaturated fat intake by 5% of your calories causes between a 3% and 17% reduction in cardiac mortality Micha.
  • Vitamin D supplements reduce mortality by 7% Autier.
  • Saturated fat intake has no effect on all-cause mortality, cardiovascular mortality, CHD mortality, CHD events, non-fatal heart attacks, or strokes. It did reduce cardiovascular disease risk by 17% Abdelhamid.
  • A-linolenic, long-chain w-3 polyunsaturated, and w-6 polyunsaturated fatty acid supplementations have no effect on mortality Chowdhury.
  • There are no RTCs examining the effect of eating butter on mortality Pimpin.
  • Increasing Omega 3 decreased mortality risk by 13%, but the p-value was ~10% Harrison and among the stronger studies, the effect was muted further.
  • Reductions in dietary fat intake do not change mortality Harcombe.
  • A literature review of the Mediterranean Diet and its components Widmer
  • To just quote Mente:

    The pooled analysis of RCTs showed that increased consumption of marine ω-3 fatty acids (RR, 0.77 [95% CI, 0.62-0.91]) and a Mediterranean dietary pattern (0.32 [0.15-0.48]) were each associated with a significantly lower risk of CHD. Higher intake of beta carotene supplements, fiber, fish, folate supplements, fruits and vegetables, and polyunsaturated fatty acids relative to saturated fatty acids, total fat, and ascorbic acid and vitamin E supplements were not significantly associated with CHD

  • A meta-analysis studied RCTs that swapped out the lipid emulsions used in hospitals, comparing standard high ω‐6 emulsions with emulsions enriched with extra ω‐3 fatty-acids. They found a 40% reduction in infection rates, a 16% reduction in the 30-day mortality rate (p~13%), and a reduction in hospital stays of ~2 days Pradelli.
From a literature review on sugar Rippe:

Multiple RCTs, as well as recent systematic reviews meta-analyses, have suggested that when sugars are substituted isocalorically for other carbohydrates and consumed in the normal range of human consumption there is nothing unique in regard to sugar consumption and health consequences.

...

It is important to point out that, however, abundant evidence exists suggesting that consumption of all energy dense nutrients, including added sugar, represents an important step along with decreased physical activity in increasing the risk of interrelated metabolic diseases such as obesity, CHD, T2D, and NAFLD.

Randomized Control Trials

Statistically significant results:
  • Eating more bread, root vegetables, green vegetables, fish, fruit, and replacing margarine with butter reduced overall and cardiac mortality Lorgeril.
  • Eating more vegetables, fruits, grains, and eating less fat reduced overall mortality Chlebowski.
  • Eating more n-3 polyunsaturated fats reduced overall and cardiac mortality Bomba.
  • A Mediterranean diet with either free olive oil or nuts reduced overall mortality Estruch.
Statistically insignificant results:
  • Reducing fat and replacing saturated fat with polyunsaturated fat reduced overall and cardiac mortality Burr.
  • Increased fatty fish consumption reduced overall mortality and reduced cardiac mortality Burr.
  • Eating more fiber increased overall and cardiac mortality Burr.
  • 1800mg of PA with Statin increased overall mortality and decreased overall cardiac mortality. Yokoyama.
  • Replacing polyunsaturated fats with saturated fats and reducing cholesterol reduced overall and cardiac mortality Leren.

And finally, Woodward performs an experiment where the treatment is advising people to eat a Mediterranean diet. However, the analysis in the paper was based on the correlation between Mediterranean-diet compliance with various outcomes. It's unclear to me how we can infer causation from that.

Hooper, L., Summerbell, C. D., Thompson, R., Sills, D., Roberts, F. G., Moore, H., & Smith, G. D. (2011). Reduced or modified dietary fat for preventing cardiovascular disease. Cochrane database of systematic reviews, (7). https://doi.org/10.1002/14651858.CD002137.pub2. Mozaffarian, D., Micha, R., & Wallace, S. (2010). Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS medicine, 7(3), e1000252. https://doi.org/10.1371/journal.pmed.1000252. Autier, P., & Gandini, S. (2007). Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Archives of internal medicine, 167(16), 1730-1737. https://doi.org/10.1001/archinte.167.16.1730. Hooper, L., Martin, N., & Abdelhamid, A. (2015). Cochrane corner: what are the effects of reducing saturated fat intake on cardiovascular disease and mortality?. https://dx.doi.org/10.1136/heartjnl-2015-308521. Chowdhury, R., Warnakula, S., Kunutsor, S., Crowe, F., Ward, H. A., Johnson, L., ... & Khaw, K. T. (2014). Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. https://doi.org/10.7326/M13-1788. Pimpin, L., Wu, J. H., Haskelberg, H., Del Gobbo, L., & Mozaffarian, D. (2016). Is butter back? A systematic review and meta-analysis of butter consumption and risk of cardiovascular disease, diabetes, and total mortality. PloS one, 11(6), e0158118. https://doi.org/10.1371/journal.pone.0158118. De Lorgeril, M., Salen, P., Martin, J. L., Monjaud, I., Delaye, J., & Mamelle, N. (1999). Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation, 99(6), 779-785. https://doi.org/10.1161/01.CIR.99.6.779. Chlebowski, R. T., Aragaki, A. K., Anderson, G. L., Thomson, C. A., Manson, J. E., Simon, M. S., ... & Barrington, W. (2017). Low-fat dietary pattern and breast cancer mortality in the Women’s Health Initiative randomized controlled trial. Journal of Clinical Oncology, 35(25), 2919. https://doi.org/10.1200/JCO.2016.72.0326. Burr, M. L., Gilbert, J. F., Holliday, R. A., Elwood, P. C., Fehily, A. M., Rogers, S., ... & Deadman, N. M. (1989). Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). The Lancet, 334(8666), 757-761. https://doi.org/10.1016/S0140-6736(89)90828-3. Yokoyama, M., Origasa, H., Matsuzaki, M., Matsuzawa, Y., Saito, Y., Ishikawa, Y., ... & Kita, T. (2007). Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. The Lancet, 369(9567), 1090-1098. https://doi.org/10.1016/S0140-6736(07)60527-3. Marchioli, R., Barzi, F., Bomba, E., Chieffo, C., Di Gregorio, D., Di Mascio, R., ... & Mantini, L. (2002). Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione. Circulation, 105(16), 1897-1903. https://doi.org/10.1161/01.CIR.0000014682.14181.F2. Estruch, R., Ros, E., Salas-Salvadó, J., Covas, M. I., Corella, D., Arós, F., ... & Lamuela-Raventos, R. M. (2013). Primary prevention of cardiovascular disease with a Mediterranean diet. New England Journal of Medicine, 368(14), 1279-1290. https://doi.org/10.1056/NEJMoa1200303. Leren, P. (1970). The Oslo diet-heart study: eleven-year report. Circulation, 42(5), 935-942. https://doi.org/10.1161/01.CIR.42.5.935. Barzi, F., Woodward, M., Marfisi, R. M., Tavazzi, L., Valagussa, F., & Marchioli, R. (2003). Mediterranean diet and all-causes mortality after myocardial infarction: results from the GISSI-Prevenzione trial. European journal of clinical nutrition, 57(4), 604. https://doi.org/10.1038/sj.ejcn.1601575. Hooper, L., Thompson, R. L., Harrison, R. A., Summerbell, C. D., Ness, A. R., Moore, H. J., ... & Riemersma, R. A. (2006). Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. Bmj, 332(7544), 752-760. https://doi.org/10.1136/bmj.38755.366331.2F. Harcombe, Z., Baker, J. S., Cooper, S. M., Davies, B., Sculthorpe, N., DiNicolantonio, J. J., & Grace, F. (2015). Evidence from randomised controlled trials did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review and meta-analysis. Open heart, 2(1). https://dx.doi.org/10.1136/openhrt-2014-000196. Widmer, R. J., Flammer, A. J., Lerman, L. O., & Lerman, A. (2015). The Mediterranean diet, its components, and cardiovascular disease. The American journal of medicine, 128(3), 229-238. https://doi.org/10.1016/j.amjmed.2014.10.014. Rippe, J. M., & Angelopoulos, T. J. (2016). Sugars, obesity, and cardiovascular disease: results from recent randomized control trials. European journal of nutrition, 55(2), 45-53. https://doi.org/10.1007/s00394-016-1257-2. Mente, A., de Koning, L., Shannon, H. S., & Anand, S. S. (2009). A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease. Archives of internal medicine, 169(7), 659-669. https://doi.org/10.1001/archinternmed.2009.38. Pradelli, L., Mayer, K., Klek, S., Omar Alsaleh, A. J., Clark, R. A., Rosenthal, M. D., ... & Muscaritoli, M. (2020). ω‐3 fatty‐acid enriched parenteral nutrition in hospitalized patients: systematic review with meta‐analysis and trial sequential analysis. Journal of Parenteral and Enteral Nutrition, 44(1), 44-57. https://doi.org/10.1002/jpen.1672.