Effect of Berberine on Cardiovascular Disease Risk Factors: A Mechanistic Randomized Controlled Trial

Abstract

Cardiovascular disease (CVD) is a major contributor to the global burden of disease. Berberine, a long-standing, widely used, traditional Chinese medicine, is thought to have beneficial effects on CVD risk factors and in women with polycystic ovary syndrome. The mechanisms and effects, specifically in men, possibly via testosterone, have not been examined previously. To assess the effect of berberine on CVD risk factors and any potential pathway via testosterone in men, we conducted a randomized, double-blind, placebo-controlled, parallel trial in Hong Kong. In total, 84 eligible Chinese men with hyperlipidemia were randomized to berberine (500 mg orally, twice a day) or placebo for 12 weeks. CVD risk factors (lipids, thromboxane A2, blood pressure, body mass index and waist–hip ratio) and testosterone were assessed at baseline, and 8 and 12 weeks after intervention. We compared changes in CVD risk factors and testosterone after 12 weeks of intervention using analysis of variance, and after 8 and 12 weeks using generalized estimating equations (GEE). Of the 84 men randomized, 80 men completed the trial. Men randomized to berberine had larger reductions in total cholesterol (−0.39 mmol/L, 95% confidence interval (CI) −0.70 to −0.08) and high-density lipoprotein cholesterol (−0.07 mmol/L, 95% CI −0.13 to −0.01) after 12 weeks. Considering changes after 8 and 12 weeks together, berberine lowered total cholesterol and possibly low-density lipoprotein-cholesterol (LDL-c), and possibly increased testosterone. Changes in triglycerides, thromboxane A2, blood pressure, body mass index and waist–hip ratio after the intervention did not differ between the berberine and placebo groups. No serious adverse event was reported. Berberine is a promising treatment for lowering cholesterol. Berberine did not lower testosterone but instead may increase testosterone in men, suggesting sex-specific effects of berberine. Exploring other pathways and assessing sex differences would be worthwhile, with relevance to drug repositioning and healthcare.

Berberine, a Herbal Metabolite in the Metabolic Syndrome: The Risk Factors, Course, and Consequences of the Disease

“…Recent clinical reports state that, in addition to the beneficial effect on the lipid profile, berberine increases the level of testosterone in men, which may reduce the risk of developing cardiovascular diseases. Importantly, previous studies have shown that berberine (1500 mg/day for 3 months) reduced testosterone in women with PCOS [8].…”

Pre-Administration of Berberine Exerts Chemopreventive Effects in AOM/DSS-Induced Colitis-Associated Carcinogenesis Mice via Modulating Inflammation and Intestinal Microbiota

“…In the last two decades, BBR has been investigated vigorously due to its manifold biological activities for anti-tumorigenic, anti-inflammatory, anti-oxidative, anti-microbial, anti-diabetic, and anti-hyperlipidemia properties [23][24][25][26]. Accordingly, the evidence from in vivo studies has confirmed that BBR exerts enormous therapeutic potential on various diseases, including cardiovascular diseases [27], metabolic diseases [28], inflammatory diseases [29] and cancers [30]. In terms of modern biomedical studies, the anti-cancer activities of BBR have been demonstrated, which were correlated to inhibit the proliferation, growth, and metastasis of tumors, including gastric cancer, pancreatic cancer, breast cancer, lung cancer, liver cancer and colorectal cancer [31].…”

Overall and sex-specific effect of berberine for dyslipidemia: systematic review and meta-analysis of placebo-controlled trials

“…A total of 16 studies met the eligibility criteria with 1,529 participants (n= 761 berberine; 768 = placebo; Table 1; Supplementary file 3 p. 2 shows records for each study). (16-18, 23, 24, 29, 31-40) All studies were conducted in young or middle-aged adults and none of the studies enrolled participants with a history of coronary artery disease or stroke. Thirteen studies (81%) were conducted in mainland China and Hong Kong.…”

“…In our randomized controlled trial in Chinese men, berberine increased serum testosterone, whereas trials in women with polycystic ovary syndrome (PCOS) showed berberine decreased testosterone concentrations. (16-18) To our knowledge, the sex-specific effect has not been considered in previous systematic reviews of berberine.…”