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Berberine Supplementation Lowers Certain Lipid Markers and Appears to Modulate Testosterone Levels

Date 10-29-2021
HC# 092121-675
Cardiovascular Disease Risk

Zhao JV, Yeung WF, Chan YH, et al. Effect of berberine on cardiovascular disease risk factors: A mechanistic randomized controlled trial. Nutrients. July 26, 2021;13(8):2550. doi:10.3390/nu13082550.

Cardiovascular disease (CVD) greatly increases the global burden of morbidity and mortality. Sex hormones have long been thought relevant to CVD because of the difference in incidence by sex. Berberine is a plant alkaloid highly concentrated in several plants, including Chinese goldthread (huanglian; Coptis chinensis, Ranunculaceae) and Chinese cork tree (huangbai; Phellodendron chinense, Rutaceae) roots, rhizomes, and stem bark to make berberine tablets. Systematic reviews and meta-analyses have demonstrated beneficial effects of berberine on CVD risk factors such as blood lipids, adiposity, and blood pressure; however, these trials vary in quality and design. Moreover, while many pathways have been proposed, the mechanisms by which berberine exerts its cardioprotective effects are unclear, despite its long history of use. As such, this randomized, parallel, double-blind, placebo-controlled trial aimed to assess the effects of berberine on CVD risk factors in men and whether changes in these risk factors were mediated by testosterone.

Staff volunteers and their family members were recruited from the University of Hong Kong (Hong Kong, China) and from a nearby outpatient clinic using advertisements, email, and distribution of leaflets. The eligibility criteria were aged 20 to 65 years; of Chinese ethnicity; hyperlipidemic; willing to make return visits; no hormone replacement therapy during the previous 12 months; no current Berberine use; free from any congenital condition and infectious disease; and no history of chronic disease.

Eligible patients were randomized to receive purified berberine tablets (500 mg orally twice per day) or placebo tablets of similar appearance for 12 weeks. Manufacturing information for active and placebo tablets was not disclosed. The dose of berberine used has been shown effective for lowering lipids in previous trials. The primary outcomes were changes in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), thromboxane A2 (TXA2), systolic (SBP) and diastolic (DBP) blood pressure, and serum testosterone. Body mass index (BMI) and waist-hip ratio (WHR) were secondary outcomes. Changes in the primary and secondary outcomes were compared and calculated after eight and 12 weeks.

Of the 135 men assessed for eligibility, 84 were evenly randomized to receive berberine or placebo. Two participants from each group withdrew due to feeling unwell and other personal reasons, leaving 40 in each group for analysis. Baseline measurements and characteristics related to demographics, education level, and lifestyle habits were similar between the groups. After 12 weeks, patients taking berberine had a larger reduction in TC (P = 0.02) and HDL-C compared with those taking the placebo (P = 0.03), with a similar effect on TC at eight weeks (P = 0.03). Using generalized estimating equations (GEE) to model the longitudinal data at both eight and 12 weeks, a similar estimate was obtained for TC with no association for HDL-C. The decrease in LDL-C (P = 0.03) and increase in testosterone (P = 0.01) were statistically significant. There were no evident differences in TGs, TXA2, SBP, DBP, BMI, or WHR. Berberine was well-tolerated with no incidence of serious adverse events.

Based on their results, the authors conclude that berberine affects CVD risk factors by lowering TC and possibly lowering LDL-C and increasing testosterone. These findings are in line with other previous studies that have demonstrated a beneficial effect of berberine on TC and possibly LDL-C. There were no significant differences in TG, blood pressure or adiposity between the groups, which is less consistent with some systematic reviews and meta-analyses. It is possible that berberine may have an effect in men with established CVD. The reduction in HDL-C may have occurred by chance at 12 weeks because a reduction was not evident using GEE model as the authors suggest, or berberine may have a significant main effect of time. In either case, replication of this study is needed.

To the authors' knowledge, their study is the first to examine the effect of berberine on testosterone levels in men. Compared with previous evidence in women with polycystic ovary syndrome (PCOS), berberine may have sex-specific effects on sex hormones. Although there was a significant increase in serum testosterone, the increase is unlikely to be of clinical significance; however, owing to the U-shape curve of testosterone levels in men and risk for CVD, there is likely no harm in this increase as the patients' serum testosterone level was far from the upper limit. Future trials may also consider also measuring free testosterone. The authors cite limitations related to the small sample size and homogeneous study population.

The authors report no conflicts of interest.

Gavin Van De Walle, MS, RDN