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Original Investigation
August 26, 2019

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

Author Affiliations
  • 1Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
  • 2Department of Food and Life Science, Azabu University, Kanagawa, Japan
  • 3Department of Food Science and Nutrition, Faculty of Human Life and Environment, Nara Women’s University, Nara, Japan
  • 4Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan
  • 5Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Suita, Japan
JAMA Intern Med. Published online August 26, 2019. doi:10.1001/jamainternmed.2019.2806
Key Points

Question  What is the long-term association between dietary protein intake and all-cause or cause-specific mortality in the Japanese population?

Findings  In this cohort study of 70 696 Japanese adults followed up for a mean of 18 years, higher intake of plant protein was associated with lower total mortality. Moreover, substitution of plant protein for animal protein, mainly for red or processed meat protein, was associated with lower risk of total, cancer-related, and cardiovascular disease–related mortality.

Meaning  A higher intake of plant-based proteins may contribute to long-term health and longevity.


Importance  Epidemiological evidence regarding the long-term effects of higher dietary protein intake on mortality outcomes in the general population is not clear.

Objective  To evaluate the associations between animal and plant protein intake and all-cause and cause-specific mortality.

Design, Setting, and Participants  This prospective cohort study included 70 696 participants in the Japan Public Health Center–based Prospective Cohort who were aged 45 to 74 years and had no history of cancer, cerebrovascular disease, or ischemic heart disease at study baseline. Data were collected from January 1, 1995, through December 31, 1999, with follow-up completed December 31, 2016, during which 12 381 total deaths were documented. Dietary intake information was collected through a validated food frequency questionnaire and used to estimate protein intake in all participants. Participants were grouped into quintile categories based on their protein intake, expressed as a percentage of total energy. Data were analyzed from July 18, 2017, through April 10, 2019.

Main Outcomes and Measures  Hazard ratios (HRs) and 95% CIs for all-cause and cause-specific mortality were estimated using Cox proportional hazards regression models with adjustment for potential confounding factors.

Results  Among the 70 696 participants, 32 201 (45.5%) were men (mean [SD] age, 55.6 [7.6] years) and 38 495 (54.5%) were women (mean [SD] age, 55.8 [7.7] years). Intake of animal protein showed no clear association with total or cause-specific mortality. In contrast, intake of plant protein was associated with lower total mortality, with multivariable-adjusted HRs of 0.89 (95% CI, 0.83-0.95) for quintile 2; 0.88 (95% CI, 0.82-0.95) for quintile 3; 0.84 (95% CI, 0.77-0.92) for quintile 4; and 0.87 (95% CI, 0.78-0.96) for quintile 5, with quintile 1 as the reference category (P = .01 for trend). For cause-specific mortality, this association with plant protein intake was evident for cardiovascular disease (CVD)–related mortality (HRs, 0.84 [95% CI, 0.73-0.96] to 0.70 [95% CI, 0.59-0.83]; P = .002 for trend). Isocaloric substitution of 3% energy from plant protein for red meat protein was associated with lower total (HR, 0.66; 95% CI, 0.55-0.80), cancer-related (HR, 0.61; 95% CI, 0.45-0.82), and CVD-related (HR, 0.58; 95% CI, 0.39-0.86) mortality; substitution for processed meat protein was associated with lower total (HR, 0.54; 95% CI, 0.38-0.75) and cancer-related (HR, 0.50; 95% CI, 0.30-0.85) mortality.

Conclusions and Relevance  In this large prospective study, higher plant protein intake was associated with lower total and CVD-related mortality. Although animal protein intake was not associated with mortality outcomes, replacement of red meat protein or processed meat protein with plant protein was associated with lower total, cancer-related, and CVD-related mortality.

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    2 Comments for this article
    Concerns about Misleading Interpretation and Incorrect Conclusion
    Angela Stanton, PhD | Stanton Migraine Protocol Inc.,
    The article by Budhathoki et al.,(1) is akin to the article  in 2016 by Song et al (2)l. A study of association is used to support causation without appropriate statistical proof.

    The article states in the abstract that “Intake of animal protein showed no clear association with total or cause-specific mortality” and then in the next sentence “In contrast, intake of plant protein was associated with lower total mortality.” If there is no clear association between meat protein and mortality, how can plant protein be associated with lower mortality? If there is no association, then there is no association.  />
    In my view, the authors main findings are incorrect, confusing, and misleading.

    This research is based on food frequency surveys for the previous year, completed once every five years. Food frequency questionnaires are questionable at best, particularly when a past year’s consumption has to be recalled.

    A frequent  error in a food frequency analysis is the substitution of plant protein for animal protein “on paper” with “isocaloric substitution interpretation,” without the subjects actually changing their diet. Such substitution cannot be used to conclude what would have happened had they actually changed their diet. So we cannot infer if their mortality changed.

    And finally, none of the hazard ratios shown meet the Bradford Criteria of 2 to suggest that the associations are significant enough to consider causation for even further analysis, let alone conclude any causal significance. This study shows no association of mortality with the type of protein consumed.

    1 Budhathoki, S. et al. Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality. JAMA Internal Medicine, doi:10.1001/jamainternmed.2019.2806 (2019).

    2 Song, M., Fung, T. T., Hu, F. B. & et al. Association of animal and plant protein intake with all-cause and cause-specific mortality. JAMA Internal Medicine 176, 1453-1463, doi:10.1001/jamainternmed.2016.4182 (2016).
    This study is very well described by the title but no clear advice could be provided
    Guy Pelouze, MD MSc | Institut de Recherche Clinique, France
    The findings of this prospective observational study could be summarized differently: Animal protein is associated with no increase or decrease of mortality neither total nor from cancer or CVD. The null hypothesis is not rejected. The authors argue that plant protein could be associated with less mortality. Apart from the validity of testing this partial hypothesis as a secondary outcome, one must recognize that the results are mitigated and surprising. As total and animal protein consumption is not associated with any change in mortality, a decrease in total and CVD mortalities associated with plant protein is improbable. Plant protein is significantly associated with a 13% decrease in all-cause mortality. No difference in mortality due to cancer. An association with a 24% decrease in cardiovascular mortality, 25% for coronary heart disease and 28% for stroke. But confounding factors are so numerous that in such a model this assertion is backed by very weak evidence. We have listed some evidences of uncertainty in the design and the follow-up:
    - A single questionnaire at the beginning of the study that lasted several years and another questionnaire five years later with modalities for taking into account information that violates the basic rules. I quote: "Since the five-year follow-up survey questionnaire contained more complete information on food consumption than the original survey, we used the five-year follow-up survey data collected from January 1, 1995, to December 31, 1999, as the basis for this analysis."
    - Weak correlation and reproducibility of questionnaires as evaluated in one small group of verification and only once at the beginning of the study.
    - No clinical evaluation about T2D during the study (minimal duration 16 years)
    - A multivariate model 1 which does not equate smokers across groups while  deaths from cancer and CVD are dealt with.
    So using a bayesian approach, what does reconcile the different findings of this study?
    My answer is ethnicity, Japanese diet and lifestyle. Japanese do have a low prevalence of CVD. They eat less meat and much more fish and seafood that Westerners. It is the case in the study. In Japan as in the West people who don't eat plants do have a less healthy lifestyle as eating plants is a marker of less proportion of processed foods. And last but not least the statistical substitution of protein leads tp the same results (and better results for cancer) when fish instead of plant protein is substituted.