Higher Intake of Protein Connected to Lower Mortality

Could a primarily plant-based high protein diet be the secret to longevity? 

Diet plays a critical role in our overall health. Numerous health conditions such as cancer and cardiovascular diseases are linked to poor diet; however, the optimal dietary components that support longevity and reduce morbidity are still debatable. 

The high-protein diet has gained a lot of popularity in recent years, mainly due to its effect on weight loss; however, conflicting data have been reported regarding the association between animal and plant protein and all-cause mortality.  

A systematic review/meta-analysis of prospective cohort studies was recently published in The BMJ, investigating the dose-response relationship between protein intake and mortality rate. 

This review was done on prospective observational studies published up to December 31st, 2019, with protein intake (total, animal, plant) as the exposure of interest and mortality (all-cause, cardiovascular, cancer) as the outcome of interest. Only studies done on adults without chronic kidney disease, end-stage cancer, or critical illness were included. Letters, reviews, meta-analyses, comments, and ecological studies were excluded.  

Non-randomized studies of exposure (ROBINS-E) tool was used to assess the risk of bias. 

Statistical analyses were conducted using STATA version 14.0.  

A P value of less than 0.05 was considered significant for all tests, including Cochran‘s Q test. 

A comparison between the highest and lowest categories of protein intake was made using odds ratios, relative risks, and hazard ratios. 

In the initial literature search, 18,683 articles were identified. Only 32 papers of cohort studies met the inclusion criteria of the systematic review, and 31 papers met the criteria of the meta-analysis.  

A total of 715,128 participants aged 19 to 101 were included in the prospective cohort studies with a follow-up range of 3.5 to 32 years.  

The included studies examined the protein intake via dietary records or recalls and food frequency questionnaires. Overnight urine urea nitrogen was used to estimate the total protein intake. 

All cohorts except one adjusted the associations for age, and most of them controlled for risk factors such as BMI, smoking, alcohol use, and physical activity. 

Eleven of the publications (304,100 participants and 60,495 deaths) showed no significant association between animal protein intake and all-cause mortality (95% CI 0.94 -1.05, P=0.86). Thirteen publications (439,339 participants and 95,892 deaths) showed an inverse association between plant-based protein intake and all-cause mortality (95% CI 0.87- 0.97, P=0.002). Twenty-one publications (480,304 participants and 72,261 deaths) showed a significant inverse association between total protein intake and all-cause mortality (95% CI 0.89 – 0.99, P=0.02). 

Ten publications (427,005 participants and 15,518 deaths) showed no clear association between total protein intake and mortality due to cardiovascular disease (95% CI 0.94 -1.03, P=0.51). Eight publications (290,542 participants and 13,667 deaths) also showed no significant association between animal protein intake and mortality due to cardiovascular disease (95% CI 0.94 -1.11, P=0.56). On the other hand, ten articles (425,781 participants and 14,021 deaths) showed an inverse association between plant protein intake and cardiovascular disease mortality (95% CI 0.80 to 0.96, P=0.003). 

No clear association was found between cancer mortality and protein intake, whether total, animal, or plant. 

The dose-response analysis showed a significant non-linear association between plant protein consumption and all-cause mortality (P=0.05). An additional 3% of energy from plant protein daily was associated with a 5% lower risk of all-cause death (95% CI 0.93 – 0.98, P<0.001), which was based on the linear dose-response analysis. 

Furthermore, an inverse association was found between plant protein consumption and mortality due to cardiovascular disease based on a non-linear dose-response analysis (P<0.001). 

Overall, this systematic review and meta-analysis demonstrated that increased intake of total protein was associated with a reduced rate of all-cause mortality. Moreover, plant protein was associated with a reduced risk of both all-cause and cardiovascular disease mortality, indicating that replacing animal protein with plant protein in one’s diet could be associated with longevity. 

Practice Pearls:  

• Numerous health conditions, such as cardiovascular disease and cancer, have been linked to a high protein diet. 
• This review assesses multiple studies to find the association between total protein, animal protein, and plant protein intake with all-cause mortality and mortality from cardiovascular disease and cancer. 
• Evidence shows that consuming a diet high in plant-based protein instead of animal protein might increase longevity and reduce cardiovascular disease mortality. 

Sina Naghshi, Omid Sadeghi, Walter C Willett, Ahmad Esmaillzadeh. Dietary intake of total, animal, and plant proteins and risk of all–cause, cardiovascular, and cancer mortality: a systematic review and dose-response meta-analysis of prospective cohort studies. BMJ. 2020 Jul 22;370:m2412. 

Fairuz Afram, PharmD Candidate, University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences 

See more about plant-based diets.