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What is the long-term association between dietary protein intake and all-cause or cause-specific mortality in the Japanese population?
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.
A higher intake of plant-based proteins may contribute to long-term health and longevity.
Epidemiological evidence regarding the long-term effects of higher dietary protein intake on mortality outcomes in the general population is not clear.
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.
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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Accepted for Publication: May 27, 2019.
Published Online: August 26, 2019. doi:10.1001/jamainternmed.2019.2806
Correction: This article was corrected on October 7, 2019, to fix an incomplete title.
Corresponding Author: Norie Sawada, MD, PhD, Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan (firstname.lastname@example.org).
Author Contributions: Drs Budhathoki and Sawada had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Budhathoki, Iwasaki, Yamaji, Ishihara, Tsugane.
Acquisition, analysis, or interpretation of data: Budhathoki, Sawada, Iwasaki, Yamaji, Goto, Kotemori, Ishihara, Takachi, Charvat, Mizoue, Iso, Tsugane.
Drafting of the manuscript: Budhathoki.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Budhathoki, Goto, Kotemori, Charvat.
Obtained funding: Tsugane.
Administrative, technical, or material support: Sawada, Takachi, Iso, Tsugane.
Supervision: Sawada, Iwasaki, Takachi, Iso, Tsugane.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by grants 23-A-31[toku], 26-A-2, and 29-A-4 from the National Cancer Center Research and Development Fund (since 2011) and a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan (from 1989 to 2010).
Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Group Members: Members of the Japan Public Health Center-based Prospective Study Group include the following: S. Tsugane (principal investigator), N. Sawada, M. Iwasaki, M. Inoue, T. Yamaji, A. Goto, T. Shimazu, H. Charvat, S. Budhathoki and M. Muto, National Cancer Center, Tokyo; H. Suzuki, Iwate Prefectural Ninohe Public Health Center, Iwate; T. Minamizono, Akita Prefectural Yokote Public Health Center, Akita; Y. Kobayashi, Nagano Prefectural Saku Public Health Center, Nagano; M. Irei, Okinawa Prefectural Chubu Public Health Center, Okinawa; M. Doi, Ibaraki Prefectural Mito Public Health Center, Ibaraki; M. Katagiri, Niigata Prefectural Nagaoka Public Health Center, Niigata; T. Tagami, Kochi Prefectural Chuo-higashi Public Health Center, Kochi; Y. Sou, Nagasaki Prefectural Kamigoto Public Health Center, Nagasaki; M. Uehara, Okinawa Prefectural Miyako Public Health Center, Okinawa; Y. Kokubo, National Cerebral and Cardiovascular Center, Osaka; K. Yamagishi, University of Tsukuba, Ibaraki; M. Noda and T. Mizoue, National Center for Global Health and Medicine, Tokyo; Y. Kawaguchi, Tokyo Medical and Dental University, Tokyo; K. Nakamura, Niigata University, Niigata; R. Takachi, Nara Women’s University, Nara; J. Ishihara, Azabu University, Kanagawa; H. Iso and T. Sobue, Osaka University, Osaka; I. Saito, Ehime University, Ehime; N. Yasuda, Kochi University, Kochi; M. Mimura, Keio University, Tokyo; and K. Sakata, Iwate Medical University, Iwate.
Additional Contributions: We thank all members of the Japan Public Health Center–based Prospective Study Group for their valuable contributions.
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