Dietary Acid Load and Human Health: A Systematic Review and Meta-analysis of Observational Studies.

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Dietary acid load (DAL) plays an important role in different aspects of human health. The aim of this meta-analysis was to systematically synthesize the observational evidence reporting on the associations between the DAL (represented by a potential renal acid load [PRAL] and net endogenous acid production [NEAP]) and a range of health outcomes. A systematic search of Medline (via PubMed), EMBASE, Scopus, and Web of Science was performed to identify eligible studies. Study screening and risk-of-bias assessment were conducted by 2 independent reviewers. The credibility of each outcome was graded based on predefined criteria: pooled effect size with corresponding 95% CI, 95% prediction interval, heterogeneity, small-study effect, and excess significance bias. In total, 118 observational studies (case-control [n = 22], cross-sectional [n = 65], and cohort [n = 31]) on 38 outcomes were included, incorporating a total population of 1 014 081 participants. Overall, 21/37 and 20/38 of the outcomes reported statistically significant effect sizes for PRAL and NEAP, respectively. The credibility of the evidence for PRAL was rated convincing (class I) for type 2 diabetes (T2D), and as highly suggestive evidence (class II) for overall cancer and systolic blood pressure. By assessing the credibility of the evidence for NEAP, T2D and overall cancer presented convincing evidence (class I) and breast cancer presented highly suggestive evidence (class II). The remaining outcomes presented class III (suggestive) or lower evidence (weak or no association). The higher acid-forming potential of diet was associated with a higher risk of T2D and overall cancer. Since this meta-analysis included observational studies and some of the associations were graded as weak, caution should be exercised in interpreting these associations. Further cohort studies are required with consideration of other factors that can cause biases. PROSPERO registration no. CRD42022336050.