Song · JAMA internal medicine 2016 · prospective cohort study · n=131342

Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality.

Cited 734 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective observational cohort study with long-term follow-up.

PubMed 27479196 · doi:10.1001/jamainternmed.2016.4182 · record verified 2026-08-29

What was done

This prospective cohort study evaluated 131,342 US healthcare professionals (85,013 women from the Nurses' Health Study followed from 1980 to 2012, and 46,329 men from the Health Professionals Follow-up Study followed from 1986 to 2012; mean age 49 years). Diet was assessed using regularly updated, validated food frequency questionnaires. Multivariable-adjusted hazard ratios (HRs) were calculated to assess the relationship between animal and plant protein intake (as percentage of energy) and all-cause and cause-specific mortality, including substitution models.

What was found

Median energy intake was 14% from animal protein and 4% from plant protein. Animal protein intake was not associated with all-cause mortality (HR 1.02 per 10% energy increment; 95% CI, 0.98-1.05; P for trend = .33), but was associated with higher cardiovascular mortality (HR 1.08 per 10% energy increment; 95% CI, 1.01-1.16; P for trend = .04). Plant protein was associated with lower all-cause mortality (HR 0.90 per 3% energy increment; 95% CI, 0.86-0.95; P for trend < .001) and lower cardiovascular mortality (HR 0.88 per 3% energy increment; 95% CI, 0.80-0.97; P for trend = .007). These associations were confined to participants with at least one unhealthy lifestyle factor (smoking, heavy alcohol use, overweight/obesity, physical inactivity) and were not evident in those without these factors. Substituting 3% of energy from plant protein for protein from processed red meat (HR 0.66; 95% CI, 0.59-0.75), unprocessed red meat (HR 0.88; 95% CI, 0.84-0.92), or egg (HR 0.81; 95% CI, 0.75-0.88) was associated with lower all-cause mortality.

Why it matters

The findings indicate that dietary protein source matters substantially for long-term health, suggesting that replacing animal protein—especially processed red meat—with plant protein may reduce mortality risk.

Limits

The study is observational, precluding causal inference, and relies on self-reported dietary questionnaires subject to measurement error. The cohort consisted entirely of US healthcare professionals, potentially limiting generalizability to broader populations. Furthermore, associations were absent in individuals without lifestyle risk factors, raising the possibility of residual confounding by overall health behaviors.

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