Association of Animal and Plant Protein Intake With Mortality

Study Questions:

What are the associations between animal and plant protein intake and all-cause and cause-specific mortality?


This prospective study included 70,696 participants in the Japan Public Health Center–based Prospective Cohort, aged 45-74 years, with no history of cancer, cerebrovascular disease, or ischemic heart disease at study baseline. Data were collected from 1995 through 1999, with follow-up completed in 2016. Dietary intake information was collected through a validated food frequency questionnaire. Participants were grouped into quintiles based on protein intake, expressed as a percentage of total energy. Hazard ratios (HRs) and 95% confidence intervals 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, 45.5% were men and 54.5% were women (mean age for each, ~56 years). During a mean follow-up of 18 years, there were 12,381 deaths due to all causes, including 5,055 from cancer, 3,025 from cardiovascular disease (CVD), 1,528 from heart disease, and 1,198 due to cerebrovascular disease. Mean intakes, expressed as percentage of total energy, were 7.7% for animal protein and 6.7% 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% (edible seeds in a pod including beans, lentils, peas, and chickpeas), vegetables (7.8%), and fruits (3.8%) for plant protein intake. 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 for quintile 2; 0.87 for quintile 5, with quintile 1 as the reference category (p = 0.01 for trend). For cause-specific mortality, this association with plant protein intake was evident for CVD-related mortality (HRs, 0.84 for quintile 2 to 0.73 for quintile 5; p = 0.002 for trend). Isocaloric substitution of 3% energy from plant protein for red meat protein was associated with lower total (HR, 0.66), cancer-related (HR, 0.61), and CVD-related (HR, 0.58) mortality; substitution for processed meat protein was associated with lower total (HR, 0.54) and cancer-related (HR, 0.50) mortality. HR for all-cause, cancer, and CVD mortality was significantly lower with isocaloric substitution of 3% energy from fish protein for red meat and processed meats but not for chicken, egg, and dairy animal protein sources.


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.


Similar findings of increased CV and total mortality associated with animal versus plant sources of protein have been reported in US studies. The strengths of this report from Asia include a large sample size with nearly two decades of follow-up for total and cause-specific mortality in a broad Japanese prospective cohort, and use of a model adjusting for age, sex, and types of fat, body mass index, smoking, alcohol, physical activity, green tea, and total calorie intake. However, the well validated dietary survey was limited to the 5-year follow-up from 1995 through 1999, after which there has been a continuous Westernization of the Japanese diet with decreasing plant food and fish and increasing bread and dairy and animal food and oil patterns. How that influenced the results is not clear. The use of 3% isocaloric energy substitution analysis is an accepted method for estimating benefit of changing dietary patterns, a statistical technique to mimic feeding studies. This approach was used to recommend that replacing saturated fats and trans fats with monounsaturated and polyunsaturated fats is more effective in preventing coronary heart disease than reducing overall fat intake by replacing it with the commonly consumed carbohydrate sources.

Clinical Topics: Cardio-Oncology, Diabetes and Cardiometabolic Disease, Prevention, Vascular Medicine, Diet, Exercise, Smoking

Keywords: Body Mass Index, Bread, Carbohydrates, Cardiotoxicity, Cerebrovascular Disorders, Chickens, Coronary Disease, Diet, Exercise, Fish Proteins, Fruit, Milk, Myocardial Ischemia, Neoplasms, Peas, Plant Proteins, Primary Prevention, Proteins, Seafood, Smoking, Tea, Vegetables

< Back to Listings