[Skip to Navigation]
Comment & Response
December 21, 2020

Protein Intake and Cause-Specific Mortality—Reply

Author Affiliations
  • 1Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
JAMA Intern Med. 2021;181(3):407-408. doi:10.1001/jamainternmed.2020.7260

In Reply We thank Ren and colleagues for their comments regarding our recent Original Investigation.1 The issues of complex nutritional components (including protein) in foods do have biological implications and can in part be addressed through statistical analyses, comparison of risk patterns, and interpretation.

We agree with the authors that protein in plant-based foods is consumed along with the other bioactive nutrients such as fiber, polyphenols, and antioxidants, and that these nutritive parts may also be associated with the outcomes of chronic diseases. In our multivariable models, we adjusted for several potential confounding factors, including dietary fiber, fruits and vegetables, and the inverse associations between plant protein, and when these were controlled for overall and cardiovascular disease (CVD) mortality remained unchanged.1 On the other hand, the pattern of the inverse associations we observed for plant protein intake and specific causes of mortality differ somewhat from those for other bioactive dietary components.2,3 For example, in the study2 mentioned by the authors, higher dietary fiber intake was significantly associated with reduced risk of overall and cause-specific mortality, including CVD, respiratory disease, and injury mortality for both sexes, and cancer mortality in men only. Additionally, our recent prospective serological analysis of the antioxidant beta-carotene based on outcomes for 29 000 men in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study found that elevated beta-carotene concentration was associated with reduced overall mortality, as well as reduced mortality from CVD, heart disease, stroke, cancer, diabetes, respiratory disease, and other causes.3 If these dietary components were responsible for the plant protein intake–mortality inverse association, we might expect broader and more similar risk patterns across the specific causes of death, yet such associations for mortality from cancer, respiratory disease, or injuries/accidents were not observed in either sex.1 Instead, we found significant inverse plant protein association only for CVD mortality, which diminishes the possibility that other bioactive nutrients, which have been associated with many if not all causes of mortality, substantially influenced our findings.

Add or change institution
1 Comment for this article
The association between plant-protein and accidental death in men is significant
George Henderson | Auckland University of technology
Note that although this response states that plant protein was not associated with causes of death other than CVD, in the study plant protein was associated (table 2) with non-CVD causes of death in men, including accidental death, HR in fully adjusted models 0.76 (0.61-0.93) p=0.009. The association was greater than that for CVD, HR 0.88 (0.81 to 0.95).[1]
There was no association between plant protein and accidental death in women, but it should be noted that women have lower risk of CVD than men, and are likely to die in accidents or violent acts caused by men rather than
This association in men is similar to that for the other bioactive dietary components in plants mentioned in this response, including fiber.
An effect of a nutrient so broad-spectrum that it includes accidental death among other causes is implausible, and it is more likely that eating less meat, and eating more fiber and plant protein, are appearing as traits of conscientious personalities who avoid risk though multiple strategies including diet, avoidance of intoxicants, infections and environmental toxins, regular health checks etc.[2]

[1] Huang J, Liao LM, Weinstein SJ, Sinha R, Graubard BI, Albanes D. Association Between Plant and Animal Protein Intake and Overall and Cause-Specific Mortality. JAMA Intern Med. Published online July 13, 2020. doi:10.1001/jamainternmed.2020.2790

[4] Hill PL, Turiano NA, Hurd MD, Mroczek DK, Roberts BW. Conscientiousness and longevity: an examination of possible mediators. Health Psychol. 2011;30(5):536-541. doi:10.1037/a0023859