Abstract
Background: Previous studies investigating protein intake in relation to mortality have provided conflicting results. Objective: We investigated the associations of dietary protein and protein sources with risk of disease death in the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study. Methods: The study population consisted of 2641 Finnish men, aged 42-60 y at baseline in 1984-1989. We estimated protein intakes with 4-d dietary records at baseline and collected data on disease deaths from the national Causes of Death Register. Cox proportional hazards regression models were used to estimate HRs and 95% CIs. Results: During the average follow-up of 22.3 y, we observed 1225 deaths due to disease. Higher intakes of total protein and animal protein had borderline statistically significant associations with increased mortality risk: multivariable-adjusted HR (95% CI) in the highest compared with the lowest quartile for total protein intake = 1.17 (0.99, 1.39; P-trend across quartiles = 0.07) and for animal protein intake = 1.13 (0.95, 1.35; P-trend = 0.04). Higher animal-to-plant protein ratio (extreme-quartile HR = 1.23; 95% CI: 1.02, 1.49; P-trend = 0.01) and higher meat intake (extreme-quartile HR = 1.23; 95% CI: 1.04, 1.47; P-trend = 0.01) were associated with increased mortality. When evaluated based on disease history at baseline, the association of total protein with mortality appeared more evident among those with a history of type 2 diabetes, cardiovascular disease, or cancer (n = 1094) compared with those without disease history (n = 1547) (P-interaction = 0.05 or 0.07, depending on the model). Intakes of fish, eggs, dairy, or plant protein sources were not associated with mortality. Conclusions: Higher ratio of animal to plant protein in diet and higher meat intake were associated with increased mortality risk. Higher total protein intake appeared to be associated with mortality mainly among those with a predisposing disease. This trial was registered at clinicaltrials.gov as NCT03221127. Am J Clin Nutr 2019;0:1–10.
Generated Summary
This prospective study, part of the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD), investigated the associations between dietary protein, protein sources, and the risk of death in a population of 2641 Finnish men aged 42-60 years at baseline (1984-1989). The study estimated protein intakes using 4-day dietary records and collected data on disease-related deaths from the national Causes of Death Register. Cox proportional hazards regression models were used to assess the associations, with adjustments for age, examination year, energy intake, and other relevant covariates. The main objective was to determine the relationship between protein consumption (total, animal, plant), protein sources (meat, dairy, fish, eggs), and disease-related mortality. The study sought to clarify conflicting results from previous research on protein intake and mortality, particularly in relation to animal-based vs. plant-based protein sources. The study also assessed whether the baseline disease status (type 2 diabetes, cardiovascular disease, or cancer) affected the associations between protein intake and mortality. The study focused on middle-aged men from eastern Finland, aiming to provide a comprehensive understanding of dietary protein’s role in mortality risk.
Key Findings & Statistics
- During an average follow-up of 22.3 years, 1225 deaths due to disease were observed.
- Higher intakes of total protein and animal protein had borderline statistically significant associations with increased mortality risk: the multivariable-adjusted HR (95% CI) in the highest compared with the lowest quartile for total protein intake = 1.17 (0.99, 1.39; P-trend across quartiles = 0.07) and for animal protein intake = 1.13 (0.95, 1.35; P-trend = 0.04).
- Higher animal-to-plant protein ratio (extreme-quartile HR = 1.23; 95% CI: 1.02, 1.49; P-trend = 0.01) and higher meat intake (extreme-quartile HR = 1.23; 95% CI: 1.04, 1.47; P-trend = 0.01) were associated with increased mortality.
- When evaluated based on disease history at baseline, the association of total protein with mortality appeared more evident among those with a history of type 2 diabetes, cardiovascular disease, or cancer (n = 1094) compared with those without disease history (n = 1547) (P-interaction = 0.05 or 0.07, depending on the model).
- Intakes of fish, eggs, dairy, or plant protein sources were not associated with mortality.
- The mean protein intake was 93.2 g/d, comprising 15.8% of energy intake (E%) and corresponding to 1.2 g protein/kg/d [1.4 g/kg of ideal body weight, with ideal body weight defined as BMI 22 (25)].
- 70.0% of total protein intake was from animal sources and 27.7% from plant sources.
- Those in the highest meat intake quartile had 23% (95% CI: 4, 47%; P-trend = 0.01) higher risk of mortality.
- Each 5 g/d higher intake of either total protein or animal protein was associated with a 3% (95% CI: 1, 5%; P = 0.01) higher mortality risk.
- Those in the highest quartile of animal-to-plant protein ratio had 23% (95% CI: 2, 49%; P-trend = 0.01) increased risk of mortality.
- Total protein intake: HR (95% CI) in the highest compared with the lowest quartile = 1.17 (0.99, 1.39; P-trend = 0.07).
- Animal protein intake: HR (95% CI) in the highest compared with the lowest quartile = 1.13 (0.95, 1.35; P-trend = 0.04).
- Animal-to-plant protein ratio: Extreme-quartile HR = 1.23; 95% CI: 1.02, 1.49; P-trend = 0.01.
- Meat intake: Extreme-quartile HR = 1.23; 95% CI: 1.04, 1.47; P-trend = 0.01.
- Among those with a disease history, each 5 g/d higher intake of total protein was associated with a 4% (95% CI: 1.01, 1.07) increased risk.
- Fish intake was not associated with mortality with the complete follow-up, it was related to increased mortality among those with a disease history with a shorter follow-up.
- Higher cheese intake was associated with lower mortality among those who were free of diseases.
Other Important Findings
- Higher ratio of animal to plant protein in the diet was associated with increased mortality risk.
- Higher meat intake was associated with increased mortality risk.
- Higher total protein intake appeared to be associated with mortality mainly among those with a predisposing disease.
- Intakes of fish, eggs, dairy, or plant protein sources were not associated with mortality.
- The association of total protein with mortality was more evident among individuals with a history of type 2 diabetes, CVD, or cancer.
- Compared to men with the lowest protein intake, men with higher total protein intake were more likely to be married and to have higher education and income levels, but they also had higher BMI and were more likely to have type 2 diabetes.
- Higher total protein intake was also associated with higher intake of fiber, polyunsaturated fatty acids, and all animal protein sources.
- Plant protein intake was not associated with mortality risk in the multivariable models.
- The association for total protein appeared to be stronger among those with disease history (HR: 1.04; 95% CI: 1.01, 1.07; per 5 g/d increase in intake in model 3) than among those without (HR: 1.01; 95% CI: 0.98, 1.04; P-interaction = 0.05 in model 2 and P-interaction = 0.07 in model 3).
- Adjustments for nutrient intakes further strengthened the association between meat and mortality (model 3).
- Associations were observed with total red meat and unprocessed red meat intake.
- Nonfermented dairy and milk intakes indicated associations with higher mortality risk in the minimally adjusted model 1, but these associations were attenuated after multivariable adjustments.
Limitations Noted in the Document
- The observational nature of the study prevents the exclusion of residual confounding.
- The study included several analyses, increasing the risk of random error.
- Dietary intakes were assessed with a single 4-day food recording, which might not capture the typical intakes of occasionally consumed foods.
- The study population consisted of middle-aged men, so the results may not be generalizable to older adults, women, or other populations.
- Reverse causality cannot be fully ruled out, especially in those with more severe forms of diseases.
Conclusion
The study’s results underscore the need for a balanced approach to dietary protein intake, emphasizing the importance of both quantity and source. The findings suggest that a high ratio of animal to plant protein intake and increased meat consumption are associated with elevated mortality risks. These outcomes appear to be more pronounced among individuals with pre-existing conditions such as diabetes, cardiovascular disease, or cancer, highlighting the vulnerability of this population. The study supports the emerging evidence that a diet rich in animal protein sources may not be optimal for long-term health. The study results also support the view that focusing on the source of protein is a relevant strategy, and it might be important to favor plant-based protein sources in diets. The findings contribute to a deeper understanding of how dietary choices impact health outcomes, particularly in relation to protein. The authors suggest that further research should examine the long-term effects of different protein sources to refine dietary recommendations for different population groups. A diet focused on more plant-based protein sources may provide health benefits. The research also points to the complex interplay between dietary choices, pre-existing conditions, and mortality risk, underscoring the importance of personalized nutrition strategies.