The effect of ascorbic acid supplementation on plasma leptin and adiponectin levels: Systematic review of in vivo and in vitro studies

Background Leptin plays a key role in regulating energy balance and lipid reserves. Leptin has a broad spectrum of regulatory actions. Adiponectin, an adipokine released by adipocytes, is recognized as an important factor in maintaining balance of blood glucose levels, lipid metabolism and insulin sensitivity. Recent studies have investigated the role of Ascorbic acid (AA) in the management of metabolic syndrome or the effect of high dose AA supplementation on serum AA, leptin and cortisol parameters. Purpose The purpose of the current systematic review was to identify associations between AA supplementation and plasma leptin and adiponectin level in vivo and in vitro setting. Methods Comprehensive systematic search was performed in the PubMed/Medline, SCOPUS, and Web of Science databases up to 14 May 2026. A total of 948 studies were initially searched, 187 from PubMed, 204 from the Web of Science, and 557 from Scopus databases. After excluding the duplicates, the remaining 435 articles were screened by reviewing the title and abstract, and 411 unrelated articles were excluded. Of the remaining 24 articles, 9 articles met our inclusion/exclusion. Results The results obtained from the in vivo studies show that AA supplementation positively influences the secretion of adiponectin hormone from adipose tissue cells. Moreover, in vivo studies reveal an inverse relationship between AA concentration and leptin secretion, suggesting that AA supplementation may reduce leptin levels. However, human studies present conflicting evidence regarding the effect of AA on leptin levels. Conclusion This systematic review demonstrates a positive relationship between AA and adiponectin and inverse relationship with leptin.