Dietary protein and multiple health outcomes: An umbrella review of systematic reviews and meta-analyses of observational studies

Numerous studies have evaluated the effects of dietary protein on specific health outcomes. The aim of our umbrella review was to summarize the existing evidence between the intake of dietary proteins and multiple health outcomes, and assess their strength and validity. Our study was registered at PROSPERO (No. CRD42021255938). We systematically searched PubMed, Embase, and Web of Science databases from inception to May 18, 2021, to identify relevant systematic reviews and meta-analyses of observational studies. The validated “A Measurement Tool to Assess Systematic Reviews” for assessing the methodological quality of included systematic reviews was utilized. For each association, we estimated the summary effect size using fixed and random effects methods, and the 95% confidence and prediction intervals. We also evaluated heterogeneity, evidence of small-study effects, and excess significance bias. Overall, 16 articles with 58 meta-analyses were included. All studies were categorized as over moderate quality. On employing the random-effects model, fourteen (24.1%) meta-analyses were found to be significant at P < 0.05, whereas only one (1.7%) remained significant at P < 10⁻⁶. Twenty-two (37.9%) meta-analyses had large or very large heterogeneity. Evidence of small–study effects and excess significance bias was found for three (5.2%) meta-analyses, respectively. One meta-analysis was supported by highly suggestive evidence, indicating that a 5% increase in energy intake from animal protein was associated with 12% higher risk of type 2 diabetes (95% confidence interval [CI]: 1.08–1.17). Of note, the intake of animal and plant proteins had different health effects on type 2 diabetes, all-cause mortality, and risk of cardiovascular disease mortality. Although the intake of dietary protein was associated with certain health outcomes, the strength of evidence was limited for most outcomes. Moreover, the source of dietary protein is an important factor that requires better consideration in future studies.