Plant-derived natural agents as dietary supplements for the regulation of glycosylated hemoglobin: A review of clinical trials.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder affecting a growing number of patients all over the world. T2DM complications are positively associated with HbA1c which is a long-term glycemic marker. Medicinal plants and their isolated phytochemicals have been extensively used as dietary supplements for the management of chronic disorders including T2DM. Current paper aims to review clinical trials evaluated the effect of phytochemicals for long-term management of T2DM considering the HbA1c level.Electronic databases including PubMed, Scopus and Cochrane were searched using the keywords "phytochemical", "extract", "herb", or "plant" and "HbA1c" or "glycosylated hemoglobin" in the title/abstract from the date of inception until May 2017. English and Persian language papers were included. References of the retrieved papers were also screened for relevant studies.Of 2435 studies, 39 relevant clinical trials were finally included in which phytochemicals including berberine, curcumin, catechin, silymarin, resveratrol, pycnogenol, isoflavones, lignans, isohumulone, saponins, corn bran hemicellulose and pinitol were examined. Berberine and silymarin had the strongest evidence regarding their effectiveness in long-term management of HbA1c; however, lack of enough toxicological studies suggests to stay on the safe side for the administration of these agents in diabetic patients.Current data regarding the efficacy of other phytochemicals are still controversial due to small follow-up period, methodological problems and small sample size. Future well-designed clinical trials are necessary to confirm the safety and efficacy of phytochemicals for long-term glycemic control of diabetic patients.