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.
Huang J, Albanes D. Protein Intake and Cause-Specific Mortality—Reply. JAMA Intern Med. 2021;181(3):407–408. doi:10.1001/jamainternmed.2020.7260
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