Abstract
OBJECTIVE To examine and quantify the potential dose-response relation between intake of total, animal, and plant protein and the risk of mortality from all causes, cardiovascular disease, and cancer. DESIGN Systematic review and meta-analysis of prospective cohort studies. DATA SOURCES PubMed, Scopus, and ISI Web of Science until December 2019, and references of retrieved relevant articles. STUDY SELECTION Prospective cohort studies that reported the risk estimates for all cause, cardiovascular, and cancer mortality in adults aged 18 or older. DATA SYNTHESIS Random effects models were used to calculate pooled effect sizes and 95% confidence intervals for the highest versus lowest categories of protein intake and to incorporate variation between studies. Linear and non-linear dose-response analyses were done to evaluate the dose-response relations between protein intake and mortality. RESULTS 32 prospective cohort studies were included in the systematic review and 31 in the meta-analysis. During the follow-up period of 3.5 to 32 years, 113 039 deaths (16 429 from cardiovascular disease and 22 303 from cancer) occurred among 715 128 participants. Intake of total protein was associated with a lower risk of all cause mortality (pooled effect size 0.94, 95% confidence interval 0.89 to 0.99, 12=58.4%, P<0.001). Intake of plant protein was significantly associated with a lower risk of all cause mortality (pooled effect size 0.92, 95% confidence interval 0.87 to 0.97, 12=57.5%, P=0.003) and cardiovascular disease mortality (pooled hazard ratio 0.88, 95% confidence interval 0.80 to 0.96, 12=63.7%, P=0.001), but not with cancer mortality. Intake of total and animal protein was not significantly associated with risk of cardiovascular disease and cancer mortality. A dose-response analysis showed a significant inverse dose-response association between intake of plant protein and all cause mortality (P=0.05 for non-linearity). An additional 3% energy from plant proteins a day was associated with a 5% lower risk of death from all causes. CONCLUSIONS Higher intake of total protein was associated with a lower risk of all cause mortality, and intake of plant protein was associated with a lower risk of all cause and cardiovascular disease mortality. Replacement of foods high in animal protein with plant protein sources could be associated with longevity.
Generated Summary
This meta-analysis and systematic review examined the relationship between the intake of total, animal, and plant proteins and the risk of all-cause, cardiovascular disease, and cancer mortality. The study included 32 prospective cohort studies and utilized random effects models to calculate pooled effect sizes and 95% confidence intervals. Dose-response analyses were performed to evaluate the relationship between protein intake and mortality. The main objective was to examine and quantify the potential dose-response relation between intake of total, animal, and plant protein and the risk of mortality from all causes, cardiovascular disease, and cancer. The research design involved a systematic review and meta-analysis of prospective cohort studies with data sources including PubMed, Scopus, and ISI Web of Science up to December 2019. The study selection focused on prospective cohort studies that reported risk estimates for mortality in adults aged 18 or older. This involved a linear and non-linear dose-response analysis to evaluate the relationship between protein intake and mortality, along with subgroup and sensitivity analyses to examine heterogeneity.
Key Findings & Statistics
- The systematic review included 32 prospective cohort studies and 31 in the meta-analysis.
- During a follow-up period of 3.5 to 32 years, there were 113,039 deaths (16,429 from cardiovascular disease and 22,303 from cancer) among 715,128 participants.
- Intake of total protein was associated with a lower risk of all-cause mortality (pooled effect size 0.94, 95% confidence interval 0.89 to 0.99, I²=58.4%, P<0.001).
- Intake of plant protein was significantly associated with a lower risk of all-cause mortality (pooled effect size 0.92, 95% confidence interval 0.87 to 0.97, I²=57.5%, P=0.003) and cardiovascular disease mortality (pooled hazard ratio 0.88, 95% confidence interval 0.80 to 0.96, I²=63.7%, P=0.001).
- Intake of total and animal protein was not significantly associated with risk of cardiovascular disease and cancer mortality.
- A dose-response analysis showed a significant inverse dose-response association between intake of plant protein and all-cause mortality (P=0.05 for non-linearity).
- An additional 3% energy from plant proteins a day was associated with a 5% lower risk of death from all causes.
- Of 29 articles on the association between intake of total protein and all cause mortality, six reported an inverse association, and the others reported no significant association.
- For the association between intake of animal protein and all cause mortality, two studies showed an inverse association.
- Moreover, seven publications showed an inverse association between intake of plant protein and all cause mortality.
- Of 29 papers on intake of total protein and all cause mortality, 21 presented sufficient data for comparison of the highest versus lowest categories of total protein intake.
- The summary effect size for all cause mortality comparing the highest and lowest intakes of total protein was 0.94 (95% confidence interval 0.89 to 0.99, P=0.02).
- For cardiovascular disease mortality, comparing the highest and lowest protein intakes, was 0.98 (95% confidence interval 0.94 to 1.03, P=0.51), indicating no clear significant association.
- For plant protein consumption, an inverse association was found with cardiovascular disease (pooled effect size comparing the highest and lowest intakes was 0.88, 0.80 to 0.96, P=0.003).
- The summary effect size for cancer mortality comparing the highest and lowest protein intakes was 0.98 (95% confidence interval 0.92 to 1.05, P=0.63), indicating no clear association.
Other Important Findings
- A significant inverse association was seen between total protein intake and all cause mortality in women.
- For cardiovascular disease mortality, a significant inverse association with total protein intake was seen in studies that did not control for total energy intake and macronutrients intake.
- For animal protein intake, a significant inverse association was seen with all cause mortality in studies with a follow up duration of less than 15 years.
- Plant protein intake was inversely associated with all cause mortality in both men and women.
- Linear dose-response meta-analysis showed no significant association between total protein intake and all cause mortality.
- Linear dose-response analysis showed no significant association between animal protein intake and all cause mortality.
- Linear dose-response analysis showed no significant association between plant protein intake and cardiovascular disease mortality.
- Non-linear dose-response analysis showed no significant association between intake of total protein and cardiovascular disease mortality.
- Non-linear dose-response analysis showed a significant non-linear association between plant protein intake and all cause mortality.
Limitations Noted in the Document
- Some studies did not consider total energy intake and BMI as covariates.
- Lack of controlling for other nutrients, such as amount and type of dietary fat.
- Different methods for dietary assessment, including food frequency questionnaires, dietary recall, and records.
- Measurement errors in dietary assessment.
- Conclusions about animal protein intake could have less generalisability to low or middle income economics.
- The study did not account for consumption of other nutrients and biologically active factors in foods containing protein.
- The influence of recall and selection bias is negligible, since all the studies included were prospective.
- The associations with animal protein intake and mortality could be due to combining protein from different animal sources.
Conclusion
The research concluded that higher intake of total protein was associated with a lower risk of all-cause mortality, and plant protein intake was associated with a lower risk of all-cause and cardiovascular disease mortality. The study emphasized that the inverse associations between plant protein intake and mortality remained significant even after accounting for energy, BMI, and macronutrients. The authors suggest that increased consumption of plant proteins aligns with current dietary recommendations and could potentially increase longevity. The study highlights that the mechanisms through which plant proteins affect human health are not fully understood but may involve favorable changes in various health markers, suggesting a protective role against cardiovascular diseases. The study also noted that the findings must be interpreted within the context of broader dietary patterns and social class, encouraging future investigations to consider these factors. The study supports the notion that replacing foods high in animal protein with plant protein sources could be associated with improved health outcomes. The researchers emphasized the importance of considering that humans do not consume single macronutrients, so dietary intake of other nutrients and biologically active factors in foods containing protein could also account for the association between protein intake and mortality. The inverse association of plant protein intake with all cause mortality remained significant in studies that controlled for energy, BMI, and macronutrients intake, and in studies with follow-up of less than 15 years and those that applied a food frequency questionnaire for dietary assessment. The findings suggest that an additional 3% of energy from plant proteins a day was associated with a 5% lower risk of death from all causes, reinforcing the benefits of prioritizing plant protein intake in dietary guidelines.
IFFS Team Summary
- Review article quantifying dose-response relationship between animal and plant protein intake with mortality risk
- 32 prospective studies in the systematic review and 31 in the meta-analysis
- n = 715 128, 113 039 deaths (16 429 from CVD and 22 303 from cancer, follow-up period 3.5 to 32 years).
- Total protein consumption (i.e. plant + animal) associated with significantly lower risk of mortality from all causes (pooled effect size 0.94, 95% confidence interval (CI) 0.89-0.99, I2=58.4%, P<0.001).
- Plant protein consumption associated with significantly lower risk of mortality from all causes (pooled effect size 0.92, 95% CI 0.87 to 0.97, I2=57.5%, P=0.003) and cardiovascular disease mortality (pooled hazard ratio 0.88, 95% CI 0.80 to 0.96, I2=63.7%, P=0.001).
- Inverse dose-response relationship between intake of plant protein and all causes of mortality (P=0.05). Each 3%/day increase in energy from plant proteins was associated with 5% lower risk of death from all causes. Therefore, it is suggested that replacing animal protein with plant-based protein foods could increase longevity
- Cross referenced in General / All Cause Mortality section and Cardiovascular Disease sections