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 PARTICIPANTSThis 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 MEASURESHazard 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 RELEVANCEIn 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.

BackgroundAcrylamide, a probable carcinogen to humans, forms during high temperature cooking. Dietary exposure to acrylamide among the Japanese population is unknown. We aimed to establish and validate a method to assess acrylamide exposure among the Japanese population using a food frequency questionnaire (FFQ) from the Japan Public Health Center-based prospective study.MethodsValidation studies for the FFQ were conducted in 1994 (Cohort I, n = 215) and 1996 (Cohort II, n = 350). The 28-day dietary records (DRs) were collected over 1 year. The FFQ was distributed before and after DR collection. Data for acrylamide exposure were based on reported measurements in Japan, and calculations considered the cooking process for specific vegetables in a home setting. Spearman’s rank correlation and weighted kappa coefficients were calculated from energy-adjusted data.ResultsMean acrylamide intake levels estimated from DRs for Cohorts I and II were 6.78 (standard deviation [SD], 3.89) µg/day and 7.25 (SD, 3.33) µg/day, and corresponding levels estimated from the FFQ were 7.03 (SD, 4.30) µg/day and 7.14 (SD, 3.38) µg/day, respectively. Deattenuated correlation coefficients for men and women were 0.54 and 0.48 in Cohort I and 0.40 and 0.37 in Cohort II, respectively. Weighted kappa coefficients were over 0.80 in all cases. The main contributing food groups from DRs were beverages, confectioneries, vegetables, potatoes and starches, and cereals.ConclusionsHigh kappa values validate the use of FFQ in epidemiological studies. The marked contribution of cooked vegetables indicates the importance of considering household cooking methods in assessing acrylamide intake levels in the Japanese population.

Acrylamide forms during cooking and is classified as a probable carcinogen in humans, mandating the need for epidemiological studies of dietary acrylamide and cancers. However, the risk of dietary acrylamide exposure to breast cancer in Japanese women has not been assessed. We investigated the association between dietary acrylamide intake and risk of breast cancer in the Japan Public Health Center‐based Prospective Study. The present study included 48 910 women aged 45‐74 years who responded to a 5‐year follow‐up survey questionnaire. Dietary acrylamide intake was assessed using a validated food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. During an average of 15.4 years of follow up, 792 breast cancers were diagnosed. Energy‐adjusted dietary acrylamide intake was not associated with the risk of breast cancer (adjusted hazard ratio for highest versus lowest tertile = .95, 95% confidence intervals: 0.79‐1.14, P‐trend = .58). Further, no significant associations were observed when stratified analyses were conducted by smoking status, coffee consumption, alcohol consumption, body mass index, menopausal status, estrogen receptor status, and progesterone receptor status. In conclusion, dietary acrylamide intake was not associated with the risk of breast cancer in this population‐based prospective cohort study of Japanese women.

A meta‐analysis published in 2015 noted a marginally increased risk of endometrial and ovarian cancers in non‐smoking women with dietary acrylamide intake, but only a few studies were included, and they were limited to Western countries. The aim of this study was to investigate the association between dietary acrylamide intake and endometrial or ovarian cancer risk in the Japan Public Health Center‐based Prospective Study (JPHC Study). In this prospective cohort study, 47 185 participants aged 45‐74 years at the follow‐up starting point in the JPHC Study were enrolled. Dietary acrylamide intake was assessed using a validated food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). In participants with endometrial and ovarian cancer, the average follow‐up periods were 15.5 and 15.6 years, respectively, and 161 and 122 cases of endometrial and ovarian cancer were diagnosed, respectively. Energy‐adjusted dietary acrylamide intake was negatively associated with endometrial cancer, but the association disappeared after adjusting for coffee consumption with an adjusted HR for the highest vs lowest tertile of 0.85 (95%CI: 0.54‐1.33). No association was observed, however, for ovarian cancer (adjusted HR, 0.77; 95%CI: 0.49‐1.23). Furthermore, after stratifying by smoking status, coffee consumption, alcohol consumption, body mass index, and menopause status, no association was observed. Dietary acrylamide intake was not associated with the risk of endometrial or ovarian cancer in Japanese women with a relatively lower dietary intake of acrylamide compared with Western populations.

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