Objective: This review examines the association between dietary protein intake and the risk of bone disease, kidney disease, and sarcopenia, aiming to inform future Dietary Reference Intakes (DRIs) updates, including the development of a Chronic Disease Risk Reduction (CDRR) reference value for protein.
Data sources: We searched MEDLINE®, Embase®, AGRICOLA, and Scopus from January 2000 to May 2024, and supplemented by citation searching of relevant reviews and original research.
Review methods: Following the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews and registering the protocol on PROSPERO (CRD42023446621), we included randomized and nonrandomized controlled trials, prospective cohort studies, and nested case-control studies that enrolled healthy participants and examined dietary protein intake without exercise. We assessed the risk of bias, performed a qualitative synthesis of studies rated as low to moderate risk of bias, and evaluated the strength of evidence.
Results: Of 11,015 studies, 82 articles detailing 81 unique studies met our inclusion criteria. Thirteen of these, rated as low to moderate risk of bias, were included in our synthesis. This included set comprised studies on bone disease (4 randomized controlled trials [RCTs] and 1 prospective cohort study), kidney disease (1 RCT), and sarcopenia (9 RCTs). The overall evidence was deemed insufficient to address the Key Questions, primarily due to a limited number of studies rated as low to moderate risk, the diversity of dietary protein interventions, and the wide range of outcomes, which made synthesizing results and comparing studies challenging. Additionally, studies used intermediate markers or sarcopenia diagnostic components rather than direct outcomes to assess disease risk. Notably, we found very scant literature addressing children and adolescents. Our analysis was informed by only one study each of the impact of dietary protein intake on bone disease risk (mixed findings) in children and adolescents, and the impact of dietary protein on kidney disease risk (no significant effects) in adults. The findings related to adult bone disease were inconsistent, with some studies indicating no effect and others suggesting benefits on bone health metrics. Studies on sarcopenia risk also reported inconsistent results concerning muscle mass, physical performance, and muscle strength.
Conclusions: The evidence gathered since 2000 on associations between dietary protein intake and the risks of bone disease, kidney disease, and sarcopenia is unclear, indicating a need for more rigorous research in these areas.