Diet and Longevity Research

[ Because nearly this entire page is based on meta-analyses, I'm ignoring my typical custom of coloring their findings in red. ]

I grew sick dealing with contradictory and unsubstantiated diet advice, so I wrote this page instead. It is a compilation of meta-analyses and literature reviews of RCTs that study how diet changes affect mortality and significant medical events like heart attacks and strokes. On occasion I also dug into meta-analyses on less dire outcomes, but I typically ignored such papers. I've collected around 90 meta-analyses in total.

I don't do any statistical analysis here like constructing confidence intervals or rejecting p-values. I don't compare methodologies. This isn't a meta-meta-analysis or a literature review. Think of it more like a survey try to extract some actionable advice.

For instance, a meta-analysis might conclude that the risk ratio is between 0.8 and 1.02 with 95% confidence. The authors will probably say something like "there was insufficient evidence to determine X's effect on overall mortality". My conclusion is that this is generally positive evidence.

Frequentist statistics is typically just Bayesian statistics with a uniform prior, so we can interpret these confidence intervals as Bayesian credible intervals. Under that interpretation, the example above suggests an expected reduction of mortality by 9% and a 95% chance the nutrient is net-beneficial, even if it technically doesn't reject the frequentist's null-hypothesis at the arbitrary 5% level.

Here's the tl;dr:

  • If you're obese (BMI > 30), losing weight reduces your risk of death by ~17%.
  • Increased ω-3 consumption reduces mortality by ~10%. The evidence is decidedly mixed for polyunsaturated fats in general.
  • Other than ω-3, most other macros have weak or mixed evidence, including saturated fat, total fat, and fiber. If you control of caloric intake, even sugar fits this description.
  • Vitamin D supplements reduce risk of death by ~7%. There is some evidence beta carotene supplements and excessive vitamin E supplements are bad. Vitamins A, B, and C have mixed evidence.
  • Salt intake increased mortality by ~25%. Zinc reduced mortality by ~8%. The evidence for selenium supplements is mixed, but it's likely net-good for men. Mortality evidence is mixed for calcium and iron, and it's minimal for magnesium and potassium, though the latter two do lower blood pressure.
  • The Mediterranean Diet is probably good. It doesn't look like fish, fruits, or vegetables matter much. No one has examined butter.
  • As far as I could tell, no meta-analysis has evaluated the effect of probiotics on mortality outside infants and the critically ill. However, benefits on other metrics have been found (e.g. blood pressure).
  • Likewise, I couldn't find any meta-analyses of coffee/caffeine on mortality but found some mixed results on various health indicators. Most researchers consider consuming less than 5 cups per day fine.

Ignoring weight loss and assuming independence, these interventions combined can cut mortality by ~42% which would increase average life expectancy by ~7 years.

Obesity

One uncontroversial fact is that weight-reducing diets among the obese reduce mortality. A 2017 meta-analysis examined RCTs of low fat, weight reducing diets. They found a risk ratio for all-cause mortality of between 0.71 and 0.95 in high-quality trials and a cardiovascular event risk ratio of between 0.83 and 1.04 Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis. Similar results were found by a 2015 meta-analysis that didn't focus on low-fat diets Kritchevsky. An earlier 2013 meta-analysis focused on low-carb weight-loss diets but, sadly, didn't find any RCTs in the literature Low-carbohydrate diets and all-cause mortality: a systematic review and meta-analysis of observational studies.

Unfortunately, almost all these RCTs were done on groups with average BMIs above 30 (the threshold of obesity), which means we can't really generalize to non-obese people. Moreover, I couldn't find any meta-analysis that examined an interaction between body fat or BMI and these mortality effects. For this reason, we can only really conclude that dieting makes obese people live longer. Its effects on people with lower BMIs is largely unknown.

That being said, I'd be remiss if I didn't mention that there is some evidence that even most non-obese people should eat less too.

Lowering my standards for just this part away from RCT meta-analyses, the correlational literature suggests some conflicting information here. A meta-analyses of longitudinal studies found optimal BMI for all-cause mortality was in the high 20s Winter, which places it in the "overweight" category. In fact, they found statistically significant increased mortality for people with BMIs below 23.0 even though the healthy range is generally considered 18.5 - 24.9.

Now, longitudinal studies of this kind suffer from a serious problem besides being merely correlational: as people approach death they often dramatically lose weight, so it shouldn't be surprising that these correlations seem biased upward from a causal-inference perspective. However, I thought this was interesting tidbit since longitudinal studies typically "predict" significantly larger effect sizes than RCTs rather than smaller ones (see e.g. the effect of exercise on mortality)

Polyunsaturated Fats

95% confidence intervals of the effect of polyunsaturated fat consumption on all-cause mortality. The sources are (in chronological order): Yzebe, Harrison, Mente, Micha, Casula, Effect of omega-3 fatty acid supplementation on cancer incidence, non-vascular death, and total mortality: a meta-analysis of randomized controlled trials, Wen, Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a systematic review and meta-analysis of primary prevention trials, Aung, and Pradelli. The studies are colored based on whether they examined ω-3 or polyunsaturated fat more generally.

As you can see from the above graph, there is decent evidence that ω-3 consumption reduces mortality, but the evidence is mixed for polyunsaturated fat in general. Here are short synopses in chronological order (again):

  • From Yzebe:

    Daily intake of omega‐3 fatty acids for a mean duration of 37 months decreased all causes of mortality by 16% (relative risk 0.84, 95% confidence interval [0.76; 0.94]) and the incidence of death due to MI by 24% (0.76, [0.66; 0.88]). No significant effect was found for the other outcomes.

  • Harrison examined the effect of ω-3 on mortality in trials of adults who were not critically ill.
  • Mente looked at a bunch of different diet studies that lasted for at least a year. Their examination of marine ω-3 fatty acids was on of many dietary attributes they considered.
  • Micha looked at polyunsaturated fat consumption on CHD endpoints. They found significant (0.70-0.95) reductions in CHD events and some decent evidence that this effect was stronger in longer trials (p=0.016). They also found reductions in CHD mortality (0.65 - 0.98).
  • From Casula:

    No statistically significant association was observed for all-cause mortality (RR, 0.89; 95% CI, 0.78 to 1.02) and stroke (RR, 1.31; 95% CI, 0.90 to 1.90). Conversely, statistically significant protective effects were observed for cardiac death (RR, 0.68; 95% CI, 0.56 to 0.83), sudden death (RR, 0.67; 95% CI, 0.52 to 0.87), and myocardial infarction (RR, 0.75; 95% CI, 0.63 to 0.88).

  • From Effect of omega-3 fatty acid supplementation on cancer incidence, non-vascular death, and total mortality: a meta-analysis of randomized controlled trials:

    Omega-3 fatty acid supplementation had no effect on cancer incidence (RR, 1.10; 95% CI: 0.97–1.24; P = 0.12), nonvascular death (RR, 1.00; 95% CI: 0.93–1.08; P = 1.00), or total mortality (RR, 0.95; 95% CI: 0.88–1.03; P = 0.24)

  • From Wen:

    Patients assigned to Omega-3 PUFAs did not demonstrate satisfactory improvements on major cardiovascular events (OR, 0.93; 95% CI, 0.86 to 1.01; P = 0.08; I2 = 46%). By contrast, the reduced risks of death from cardiac causes, sudden cardiac death and death from all causes (OR, 0.88; 95% CI, 0.80 to 0.96; P = 0.003; I2 = 0%; OR, 0.86; 95% CI, 0.76 to 0.98; P = 0.03; I2 = 29%; and OR, 0.92; 95% CI, 0.85 to 0.99; P = 0.02; I2 = 6%; respectively) were shown.

  • Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a systematic review and meta-analysis of primary prevention trials looked at RCTs over a year in length that studied dietary supplements in non-pregnant non-elderly adults. If drugs were used concurrently both the control and intervention groups needed the same drug. Like, Mente they considered many different supplements, but one was EPA. They didn't find reductions in all-cause, cardiovascular mortality (0.56 - 1.55), or risk of cancer (0.93 - 1.33). They found larger effects for older people (p=0.02) and people who hadn't had a stroke before (p=0.06), but no difference by sex, prior CHD, diabetes, cholesterol, lipoprotein cholesterol, triglycerides, or prior statin use. Unfortunately, they found blinded trials saw smaller CHD mortality effects than non-blind trials (p=0.03) such that the effect pretty much disappeared (0.91 - 1.07).
  • Aung looked only at 10 large RCTs of ω-3's supplements effect on mortality. They found an almost significant reduction in CHD events (0.90 - 1.01) and CHD death (0.85 - 1.01). There was no reduction in stroke (0.93 - 1.13) or revascularization events (0.95 - 1.03) Marine ω-3 did not reduce heart attacks or any major vascular events.
  • Pradelli looked at RCTs where ω‐3 was substituted for some of the ω‐6 in hospital lipid emulsions. They found several significant reductions in days-in-ICU (0.42 - 3.49), days in hospital (1.36 - 2.93) and reductions in risk of infection (0.49 - 0.72) or sepsis (0.28 - 0.70).

Finally Chowdhury did not estimate the effect on all-cause mortality, but did find reduced risk for coronary heart disease from ω-3 (0.86 - 1.03) but not for ω-6 (0.71 - 1.12) or alpha-linolenic (0.69 - 1.36).

Other Macronutrients

  • From a meta-analysis on saturated fat Sills:

    Reducing saturated fat by reducing and/or modifying dietary fat reduced the risk of cardiovascular events by 14% (RR 0.86, 95% CI 0.77 to 0.96, 65,508 participants...)

    ...

    there were no clear effects of dietary fat on total mortality (RR 0.98, 95% CI 0.93 to 1.04, 71,790 participants) or cardiovascular mortality (RR 0.94, 95% CI 0.85 to 1.04, 65,978 participants).

  • 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.
  • High fat intake neared significance in increasing mortality Mente.
  • Fiber probably had no effect, but has p=0.14 for increasing mortality (0.96 - 1.29) Mente. Another meta-analysis found insufficient studies to evaluate the effect of fiber on mortality or cardiovascular events.
  • Reductions in dietary fat intake do not change mortality Evidence from randomised controlled trials did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review and meta-analysis Evidence from randomised controlled trials does not support current dietary fat guidelines: a systematic review and meta-analysis
  • 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.

Vitamin Supplements

There are frankly too many meta-analyses of vitamins' effects on mortality. Even after ignoring analyses examining specifically the ill, infants, pregnant women, or people from low-income countries, I've found 30 so far and wrote very brief summaries of most of them. I've decided to briefly summarize these summaries here and not cite specific meta-analyses for these claims. If you're interested, just click on the link.

  • Multivitamins: Multivitamin supplements had no statistically significant effect on all-cause mortality or mortality with either vascular or cancerous causes. There was a trend towards significance in primary prevention trials.
  • Antioxidants: The antioxidant vitamins are vitamin E, vitamin C, and beta-carotene. When examined together, there have been no found statistically significant effects and some of the signs suggested they were net-harmful.
    • Vitamin E: Of the 11 meta-analyses, all found an overall effect that wasn't statistically significant. The most recent 4 had point estimates suggesting Vitamin E increases mortality. However, most studies used doses far in excess of USDA recommendations and (in my experience) far in excess of what typical consumer vitamin supplements provide. Several studies explored mortality relating to dosage and one found a statistically significant reduction in mortality at lower dosages. So, most likely, typical vitamin E supplementation is neutral or slightly positive.
    • Vitamin C: Of the 3 meta-analyses, none found a statistically significant effect of vitamin C on mortality.
    • Beta carotene: Of the 3 meta-analyses, two found statistically significant increases in mortality. One found this effect disappeared for nonsmokers, and one found it disappeared for doses below 9.6 mg.
  • Vitamin A: One meta-analysis found a risk ratio of between 0.97 and 1.18, weakly suggesting vitamin A supplements are bad. Another found significant mortality improvements relating to infectious diseases. Maybe the solution is to only take vitamin A if you have an infectious illness? A literature review concluded that mass vitamin A supplement isn't obviously good or bad in countries at risk for vitamin A deficiency. The case for vitamin A supplements probably varies greatly by a number of context-related factors Benn.
  • B Vitamins: 2 meta-analyses found no statistically significant effects on cardiovascular or overall mortality. One did find a statistically significant reduction in strokes.
  • Vitamin D: A majority of the 8 meta-analyses analyses rejected the null hypothesis with the median point-estimate suggesting 14% reductions in all-cause mortality.

Minerals

  • Salt: A meta-analysis of salt intake RCTs estimated an all-cause mortality risk ratio between 0.40 and 1.12 for normotensive people. They found a reduction in cardiovascular mortality (0.45 - 1.01) and cardiovascular events (0.57 - 1.01). The risk ratio of cardiovascular events for normotensives was between 0.64 and 1.10 Reduced dietary salt for the prevention of cardiovascular disease. A second meta-analysis dropped one of the trials and found a statistically significant 20% reduction in cardiovascular events Salt reduction lowers cardiovascular risk: meta-analysis of outcome trials.
  • Selenium: One meta-analysis found a risk ratio of between 0.64 and 0.92 for men getting cancer but not for women. They also found a risk ratio of between 0.65 and 0.94 for cancer mortality Bardia. Another found a nearly significant reduction in CHD mortality (0.67 - 1.02) The effect of selenium supplementation on coronary heart disease: a systematic review and meta-analysis of randomized controlled trials. A third looked only at patients with sepsis syndrome and found significant improvements Alhazzani. A fourth computed risk ratios for all-cause mortality (0.85 - 1.01), cardiovascular mortality (0.74 - 1.06), cardiovascular disease (0.94 - 1.07), cancer mortality (0.53 - 1.40), and cancer incidence (0.68 - 1.07) Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a systematic review and meta-analysis of primary prevention trials.
  • Zinc: One meta-analysis found a risk ratio of between 0.82 and 1.03 Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a systematic review and meta-analysis of primary prevention trials.
  • Magnesium: One meta-analysis found laughably wide confidence intervals Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a systematic review and meta-analysis of primary prevention trials.
  • Iron: A meta-analysis examined patients with heart failure and iron deficiency and found minimal effect on mortality (0.42 - 1.57) but found significant reductions in hospitalization (0.16 - 0.49) Qian. Another analysis examining patients undergoing hip or knee surgery found no effect on mortality (0.72 - 3.69) or adverse events (0.60 - 16.28) Efficacy and safety of iron supplementation for the elderly patients undergoing hip or knee surgery: a meta-analysis of randomized controlled trials. A fourth meta-analysis examined critically ill adults they found a risk ratio between 0.43 and 2.52 Shah.
  • Calcium: One meta-analysis found a risk ratio of between 0.48 and 1.53 Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a systematic review and meta-analysis of primary prevention trials. Another found an increase in heart attacks (1.02 - 1.67) and strokes (0.96 - 1.50), but the evidence was weaker on all cause death (0.96 - 1.23) Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. A third found no statistically significant results Calcium intake and cardiovascular disease risk: an updated systematic review and meta-analysis. A fourth meta-analysis found no significant reduction in cancer mortality (0.74 - 1.24) or 3 types of cancer, but did find a reduction in prostate cancer (0.30 - 0.96) Bristow. A meta-analysis of calcium blockers in patients with hypertension found the blockers reduced strokes (0.76 - 0.99) and heart attacks (0.76 - 0.98) but increased the risk of heart failure (0.99 - 1.98). They found no effect on overall death (0.91 - 1.07) Calcium Channel Blocker Compared With Angiotensin Receptor Blocker for Patients With Hypertension: A Meta‐Analysis of Randomized Controlled Trials.
  • Potassium: I was unable to find any meta-analyses on the effect of potassium on mortality. I found a couple showing it lowers blood pressure Whelton Potassium supplementation for the management of primary hypertension in adults and one that found potassium lowered blood pressure when paired with magnesium Combined calcium, magnesium and potassium supplementation for the management of primary hypertension in adults, though it didn't examine whether the magnesium actually helped.
  • Magnesium: Speaking of, I was also unable to find any meta-analyses on the effect of magnesium on mortality. I found two showing it lowers blood pressure Effects of magnesium supplementation on blood pressure: a meta-analysis of randomized double-blind placebo-controlled trials Magnesium supplementation for the management of essential hypertension in adults.
  • Iron: I found one meta-analysis that found no effect on all-cause mortality but found some other positive health effects Clevenger.
  • Foods/Diets

    • There are no RTCs examining the effect of eating butter on mortality Pimpin.
    • One meta-analysis found adhering to a Mediterranean diet reductions in cardiovascular disease, but not in cardiovascular deaths or all-cause deaths. Al-Ghamdi. Another found reductions in vascular events, coronary events, strokes, and heart failures, but not all-cause mortality Liyanage. A third found reductions in CVD and heart attacks Becerra-Tomás. I also found two meta-analyses and a literature review examining the effect of components of the Mediterranean Diet, however these each relied heavily on correlational data A comprehensive meta-analysis on evidence of Mediterranean diet and cardiovascular disease: are individual components equal? Adherence to Mediterranean diet and risk of cancer: an updated systematic review and meta-analysis Widmer. Long-story short, the Mediterranean diet definitely reduces cardiovascular deaths, but evidence for an overall effect is weak. My private musing is that this suggests most of the Mediterranean diet is probably not longevity-promoting since one of the hallmarks of the Mediterranean diet is high ω-3 intake, which (as discussed earlier) we have good reason to believe reduces all-cause mortality by ~10%. This combined with the more muted results for the Mediterranean diet suggest to me that, more likely than not, the other aspects of the Mediterranean diet aren't very valuable.
    • Fish, fruits, and vegetables had no statistically significant effect on mortality Mente.

    Other

    • Point estimates for the effect of probiotics on mortality look good, but the results aren't statistically significant. Still, probiotics probably help critically ill adults Barraud Manzanares Pitsouni Siempos Effects of probiotic therapy on hepatic encephalopathy in patients with liver cirrhosis: an updated meta-analysis of six randomized controlled trials. The vast majority of meta-analyses I found concerned infants or the critically ill. I found several more in both categories that I didn't both looking into. The found no mortality-related meta-analysis that didn't specifically focus on those two groups. I found a couple that focused on non-mortality effects. For instance, Effects of probiotics consumption on lowering lipids and CVD risk factors: a systematic review and meta-analysis of randomized controlled trials found that probiotics reduced cholesterol and low-density lipoproteins, that yogurt was better than pills, and that multiple strains was better than a single strain. Effect of probiotics on blood pressure: a systematic review and meta-analysis of randomized, controlled trials found probiotics reduced blood pressure and reduced it more when blood pressure was high and when multiple species were consumed. McFarland found reductions in traveler's diarrhea.
    • I haven't been able to find any studies estimating the effect of caffeine on mortality of any kind. I found a literature review O'Keefe and three meta-analysis Effects of probiotic therapy on hepatic encephalopathy in patients with liver cirrhosis: an updated meta-analysis of six randomized controlled trials Wikoff Coffee, caffeine, and health outcomes: an umbrella review that I'm having a hard time summarizing except to say that consuming less than 4 cups of coffee per day is probably not very harmful and may actually be beneficial to long-term health - though that is an oversimplification.
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