Abstract
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.
Generated Summary
This prospective cohort study, conducted within the Japan Public Health Center-based Prospective Cohort, investigated the associations between animal and plant protein intake and all-cause and cause-specific mortality. The study included 70,696 participants aged 45 to 74 years who had no history of cancer, cerebrovascular disease, or ischemic heart disease at 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. The primary outcomes were hazard ratios (HRs) and 95% CIs for all-cause and cause-specific mortality, estimated using Cox proportional hazards regression models with adjustment for potential confounding factors. The analysis also evaluated the effects of substituting different protein sources for each other to assess the impact on mortality outcomes.
Key Findings & Statistics
- 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).
- Mean (SD) intakes, expressed as percentage of total energy, were 7.7% (2.7%) for animal protein and 6.7% (1.4%) for plant protein.
- Fish and seafood products (47.1%), red meats (19.4%), milk or dairy products (16.7%), and eggs (9.5%) were the major sources of animal protein intake compared with cereals (50.3%), pulses (24.1%), vegetables (7.8%), and fruits (3.8%) for plant protein intake.
- Participants with higher intake of protein from animal and plant sources were less likely to be men (34.1% and 30.5%, respectively), less likely to smoke (23.5% and 21.5%, respectively) and consume alcohol (33.3% and 21.9%, respectively), and more likely to regularly drink green tea (50.7% and 57.2%, respectively) than participants with lower protein intake.
- Compared with participants with lower intake, those with higher animal protein intake tended to consume more total energy (mean [SE], 2287 [4.9] kcal/d) and fat (mean [SE], 32.0% [0.04%]) but less carbohydrates (mean [SE], 47.1% [0.1%]), whereas those with higher plant protein intake tended to consume less total energy (mean [SE], 1914 [5.0] kcal/d) and fat (mean [SE], 22.9% [0.1%]) but more carbohydrates (mean [SE], 60.0% [0.1%]).
- As expected, compared with those in the lowest quintile of plant protein intake, participants in the highest quintile had higher intakes of soy foods (mean [SE], 144 [0.5] g/d), fruits (mean [SE], 237 [1.3] g/d), and vegetables (mean [SE], 253 [1.0] g/d) but lower intake of meat (mean [SE], 33.0 [0.3] g/d).
- Compared with those in the lowest quintile of animal protein intake, those in the highest quintiles had higher intake of meats (mean [SE], 60.6 [0.3] g/d) but lower intake of fruits (mean [SE], 180.8 [1.3] g/d), vegetables (mean [SE], 198.0 [1.0] g/d), and soy foods (mean [SE], 78.0 [0.6] g/d).
- Higher total and animal protein intake was not associated with overall mortality or cause-specific mortality.
- Plant protein intake 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.
Other Important Findings
- The study found no clear association between animal protein intake and total or cause-specific mortality.
- Isocaloric substitution of 3% energy from plant protein for red meat protein was associated with lower total, cancer-related, and CVD-related mortality.
- Substitution of plant protein for processed meat was also associated with lower total and cancer-related mortality.
- Substitution of fish protein for red meat was associated with lower total, cancer-related, and CVD-related mortality.
- Substitution of fish protein for processed meat was also associated with lower total and cancer-related mortality.
- No clear association was observed when vegetable and fruit protein were substituted for cereal or soy protein.
Limitations Noted in the Document
- The study’s strengths include its population-based design, prospective data collection, use of validated questionnaires, large sample size, and long follow-up.
- The correlation coefficient for validity for protein intake was moderate to low.
- Dietary information was based on a single assessment at baseline, and dietary habits might have changed over time.
- Any misclassification in exposure assessment is likely to have been nondifferential and would likely have attenuated risk estimates.
- Plant protein intake may represent a healthy eating behavior; although adjustment for lifestyle factors showed little difference in the overall results, the possibility of residual confounding in the association between plant protein and mortality remains.
Conclusion
In this large prospective study, higher plant protein intake was associated with lower total and CVD-related mortality. Furthermore, replacement of red or processed meat protein with plant protein was associated with a decreased risk of total, cancer-related, and CVD-related mortality. The study suggests that encouraging diets with higher plant-based protein intake may contribute to long-term health and longevity. These findings support previous research indicating that a higher intake of plant-based proteins can have beneficial health effects. The data indicates that shifting from animal protein, particularly red and processed meats, towards plant-based sources could improve long-term health outcomes, including reduced overall mortality. The study’s emphasis on isocaloric substitution provides a valuable perspective, suggesting that the benefits are not just from increasing protein intake, but also from the specific sources. For instance, the substitution of plant protein for red meat was linked to a significant reduction in overall mortality risk. The data shows that plant protein intake appears to be a beneficial dietary factor, especially when it replaces less healthy protein sources like red and processed meats, in terms of long-term health and longevity. This highlights the potential for dietary interventions to promote better health outcomes, particularly in areas related to cardiovascular disease and cancer. The results also bring attention to the importance of considering the source of protein in dietary recommendations and further research in this area.