Abstract
High dietary protein diets are widely used to manage overweight and obesity. However, there is a lack of consensus about their long-term efficacy and safety. Therefore, the aim of this study was to assess the effect of long-term high-protein consumption on body weight changes and death outcomes in subjects at high cardiovascular risk. A secondary analysis of the PREDIMED trial was conducted. Dietary protein was assessed using a food-frequency questionnaire during the follow-up. Cox proportional hazard models were used to estimate the multivariate-adjusted hazard ratio (HR) and 95% confidence intervals (95%CI) for protein intake in relation to the risk of body weight and waist circumference changes, cardiovascular disease, cardiovascular death, cancer death and total death. Higher total protein intake, expressed as percentage of energy, was significantly associated with a greater risk of weight gain when protein replaced carbohydrates (HR: 1.90; 95%CI: 1.05, 3.46) but not when replaced fat (HR: 1.69; 95%CI: 0.94, 3.03). However, no association was found between protein intake and waist circumference. Contrary, higher total protein intake was associated with a greater risk of all-cause death in both carbohydrate and fat substitution models (HR: 1.59; 95%CI: 1.08, 2.35; and HR: 1.66; 95%CI: 1.13, 2.43, respectively). A higher consumption of animal protein was associated with an increased risk of fatal and non-fatal outcomes when protein substituted carbohydrates or fat.
Generated Summary
This study analyzed the relationship between long-term high protein intake and body weight changes and mortality in older adults at high cardiovascular risk. The research utilized data from the PREDIMED trial, a multicenter, controlled, randomized clinical trial conducted on 7447 older adults. The study’s objective was to assess the effects of long-term high-protein consumption on body weight changes and death outcomes in subjects at high cardiovascular risk. Dietary protein intake was assessed using a food-frequency questionnaire during the follow-up period, and Cox proportional hazard models were used to estimate the multivariate-adjusted hazard ratio (HR) and 95% confidence intervals (95%CI) for protein intake in relation to the risk of body weight and waist circumference changes, cardiovascular disease, cardiovascular death, cancer death, and total death. The study employed a secondary analysis of the PREDIMED trial to investigate how different sources of protein intake (total, animal, and vegetable) correlate with weight gain, waist circumference changes, and various mortality outcomes, in a population with high cardiovascular risk. The primary aim was to determine the long-term safety and efficacy of high-protein diets, which are often recommended for weight management, and to assess their effects on body weight changes and mortality.
Key Findings & Statistics
- Weight Gain and Protein Intake: Higher total protein intake, expressed as a percentage of energy, was significantly associated with a greater risk of weight gain when protein replaced carbohydrates (HR: 1.90; 95%CI: 1.05, 3.46) but not when it replaced fat (HR: 1.69; 95%CI: 0.94, 3.03).
- All-Cause Death and Protein Intake: Higher total protein intake was associated with a greater risk of all-cause death in both carbohydrate and fat substitution models (HR: 1.59; 95%CI: 1.08, 2.35; and HR: 1.66; 95%CI: 1.13, 2.43, respectively).
- Animal Protein and Outcomes: A higher consumption of animal protein was associated with an increased risk of fatal and non-fatal outcomes when protein substituted carbohydrates or fat.
- Protein and Cardiovascular Events: Total dietary protein intake showed no significant association with cardiovascular events.
- Protein Intake Categories: Those in the highest quintile of total dietary protein intake showed a significant 90% greater risk of increasing body weight (higher or equal to 10%) than those in the reference quintile (third quintile). Risk of body weight gain was significantly higher in the high-protein intake group than in the normal group, when protein replaced carbohydrates (HR: 2.03; 95% CI: 1.07, 3.86: P q-trend = 0.03; HR: 1.87; 95% CI: 0.99, 3.53; P q-trend = 0.03, respectively), even after adjusting for potential confounders.
- Mortality Risk and Protein Intake: Participants in the highest quintile of dietary protein intake had a 59% and 66% greater risk of all-cause death than those in the middle quintile in the carbohydrate and fat substitution models respectively.
- Cardiovascular Events and Protein Intake: No significant association was found between the source of protein and BW changes, although subjects in the lowest quintile of vegetable protein showed an unexpected lower risk of weight loss and both WCBMI incidence and reversion in carbohydrate and fat substitution models.
- Hazard Ratios for Cardiovascular Events: In the highest quintile of total protein intake, the hazard ratio for all-cause death was 1.66 (95% CI: 1.13, 2.43) and 1.59 (1.08, 2.35) in fat and carbohydrate substitution models respectively. Higher intake of g protein/kg BW/d category (1.5 g or more) showed HR of 2.77 (1.35, 5.68) for cardiovascular and 1.66 (1.13, 2.43) for all-cause death. Animal protein intake was positively associated with cardiovascular and cancer mortality, also a positive association with cancer mortality and all-cause death for animal-to-vegetable protein ratio.
- Animal Protein and Mortality: Subjects in the highest quintile of animal protein showed a significant risk for cardiovascular events, cancer death and all-cause death.
Other Important Findings
- The study found no significant association between total dietary protein intake and changes in waist circumference.
- No significant associations were observed between total dietary protein intake and changes in either body weight or WCBMI when total protein intake was evaluated as g/kg BW/d.
- Risk of body weight gain was significantly higher in the high-protein intake group than in the normal group.
- The study also found that the association between protein intake and all-cause mortality was stronger when the protein intake was greater than 20% of total energy.
- The intake of >1.5 g protein/kg BW/d was associated with increased risk of cardiovascular and all-cause death.
- Higher animal protein consumption was associated with increased risk of cardiovascular event and cardiovascular, cancer and total death.
- A higher animal-to-vegetable protein ratio was associated with an increased risk of cancer death and all-cause death.
- A higher intake of vegetable protein was associated with a lower risk of weight loss.
Limitations Noted in the Document
- The study was conducted in a population with high cardiovascular risk, so the findings may not be generalizable to the broader population.
- The study is an observational cohort analysis of a clinical trial, and residual confounding from unmeasured factors cannot be completely ruled out.
- The lack of specific measurements of body composition could limit findings.
- The range of protein intake evaluated was relatively narrow, potentially limiting the assessment of the effects of very high-protein diets.
- The potential for residual confounding from dietary intervention cannot be discounted.
Conclusion
The findings indicate that long-term high protein intake is associated with an increased risk of weight gain and overall mortality in the study population. The data suggests that long-term use of high protein diets should be approached with caution, particularly in individuals at high cardiovascular risk. The results highlight the need for further research, including molecular and clinical studies, to better understand the mechanisms by which protein quantity and source affect body composition and health outcomes. The research stresses the importance of dietary protein sources, with animal protein consumption showing associations with adverse cardiovascular outcomes. The study’s findings support the view that dietary protein from animal sources can have negative health consequences, while the impact of vegetable protein appears less detrimental. The study results emphasize that the benefits of high protein diets might not extend to long-term health, especially among populations at risk for cardiovascular disease, underscoring the need for personalized dietary advice that takes into account both the quantity and source of protein intake. The research results highlight that the long-term effects of high protein diets, particularly those emphasizing animal protein, should be carefully considered. Overall, the study indicates that dietary recommendations need to be individualized, accounting for protein source to provide more effective and safer nutritional advice.