Background Increased protein intake has been suggested to improve gains in muscle mass and strength in adults. Furthermore, the timing of protein intake has been discussed as a margin of opportunity for improved prevention measures. Objective This systematic review investigated the effect of protein supplementation on body composition and muscle function (strength and synthesis) in healthy adults, with an emphasis on the timing of protein intake. Methods Randomized controlled trials were identified using PubMed, Web of Science, CINAHL, and Embase, up to March 2019. For meta-analyses, data on lean body mass (LBM), handgrip strength, and leg press strength were pooled by age group (mean age 18–55 or >55 y) and timing of protein intake. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. Results Data from 65 studies with 2907 participants (1514 men and 1380 women, 13 unknown sex) were included in the review. Twenty-six, 8, and 24 studies were used for meta-analysis on LBM, handgrip strength, and leg press strength, respectively. The protein supplementation was effective in improving (mean difference; 95% CI) LBM in adults (0.62 kg; 0.36, 0.88) and older adults (0.46 kg; 0.23, 0.70), but not handgrip strength (older adults: 0.26 kg; −0.51, 1.04) and leg press strength (adults: 5.80 kg; −0.33, 11.93; older adults: 1.97 kg; −2.78, 6.72). Sensitivity analyses removing studies without exercise training had no impact on the outcomes. Data regarding muscle synthesis were scarce and inconclusive. Subgroup analyses showed no beneficial effect of a specific timing of protein intake on LBM, handgrip strength, and leg press strength. Conclusion Overall, the results support the positive impact of protein supplementation on LBM of adults and older adults, independently of intake timing. Effects on muscle strength and synthesis are less clear and need further investigation. This systematic review was registered on PROSPERO as CRD42019126742.

GGMs are a powerful exploratory method that can be used to construct dietary networks representing dietary intake patterns that reveal how foods are consumed in relation to each other. GGMs indicated an apparent major role of red meat intake in a consumption pattern in the studied population. In the future, identified networks might be transformed into pattern scores for investigating their associations with health outcomes.

Our findings provide epidemiological evidence for a positive relationship between FGF23 and risk of HF. The role of PTH in the development of HF remains unclear, in particular in obese individuals, until further confirmation in other studies. 25(OH)D3 was not related to HF.

Our results indicate an increased cardiovascular risk for gallstone formers, which cannot be counteracted by gallbladder removal and opens up perspectives for individualized prevention strategies.

The tMED was not significantly associated with HF risk, but low meat, high fish and moderate alcohol intake were inversely associated with HF risk in our non-Mediterranean population. Minor dietary changes could be valuable primary prevention measures, particularly the increase of fish consumption while reducing the intake of meat.