Inorganic nitrate, a natural anti-obesity agent: A systematic review and meta-analysis of animal studies

Evidence for potential effects of inorganic nitrate (NO₃) on body weight is limited to inconsistent findings of animal experiments. In this systematic review and meta-analysis, we aimed to quantify the overall effect of inorganic NO₃, administered via drinking water, on body weight gain in rats. We searched PubMed, Scopus, and Embase databases, and the reference lists of published papers. Experiments on male rats, reported data on body weight in NO₃-treated animals and controls, were included for quality assessment, meta-analyses, subgroup anal-yses, and meta-regressions. Of 173 initially obtained studies, 11 were eligible to be included in the analyses, which covered the years 2004 to 2019 and included a total of 43 intervention (n=395) and 43 control (n=395) arms. Overall, the final body weights were significantly lower in the NO₃-supplemented groups compared to controls (WMD= –16.8 g, 95 % CI= –27.38, –6.24; P=0.002). Doses of NO₃ higher than the median (> 72.94 mg L^-1 d^-1) and longer NO₃ exposure (> 8 weeks) resulted in greater mean differences (WMD= –31.92 g, 95 % CI= –52.90, –10.94 and WMD= –23.16 g, 95 % CI= –35.64, –10.68 g). After exclusion of experiments using high doses of NO₃ (> 400 mg L^-1 d^-1), the overall mean differences in body weights between the groups decreased by approxi-mately 37 % but remained statistically significant (WMD= –10.11 g, 95 % CI= –19.04, –1.19, P=0.026). Mean changes in body weight were affected by age, baseline values in body weight, and the duration of the studies. These preliminary experimental findings strongly support the hypothesis that NO₃ can be considered as a natural anti-obesity agent.