Combined berberine and probiotic treatment as an effective regimen for improving postprandial hyperlipidemia in type 2 diabetes patients: a double blinded placebo controlled randomized study.

The short version

This randomized trial with 365 adults who had newly diagnosed type 2 diabetes explored whether combining berberine, a plant compound extracted from the Chinese herb Coptis chinensis (Huanglian), with a probiotic mix lowers postprandial lipidemia, the rise in blood fats and cholesterol after a meal. The authors note that cholesterol measured after eating is also an important heart-disease risk marker, that after-meal blood fats are common in diabetes, and that very few treatments target them. Berberine was already known to lower fasting cholesterol, but whether it helps after meals was unknown. Probiotics are live bacteria, and the nine-strain mix here included Bifidobacterium breve. This analysis came from a 12-week, double-blind, placebo-controlled trial at 20 centers in China, with 365 participants split into four groups: placebo (91), probiotics alone (92), berberine alone (84), and both (98). Participants were drug-naive adults aged 20 to 70, averaging about 52. They took berberine pills twice daily before meals, and probiotic powder once daily at bedtime. After a standard 100 g carbohydrate meal, blood drawn 120 minutes later measured cholesterol and triglycerides, and stool samples tracked gut bacteria. Only the combination significantly cut after-meal total cholesterol (24.29 mg/dL drop versus 8.66 with placebo, adjusted P = .001, a gap that chance is very unlikely to explain) and after-meal LDL cholesterol (16.54 versus 7.35 mg/dL, P = .043). Berberine alone and probiotics alone did not differ significantly from placebo for these two measures. After-meal triglycerides fell with berberine alone (P = .037) and the combination (P = .035) equally, so probiotics added nothing there, and HDL (good) cholesterol did not differ between groups. Thirty-one blood lipid molecules changed only with the combination, versus eight with berberine and two with probiotics. In stool, B. breve rose with the combination, and higher levels went with lower after-meal cholesterol. In lab dishes, berberine slowed B. breve growth but switched on its fatty-acid-uptake genes (called fadD). Adverse events were not reported in this paper. The authors conclude that berberine plus probiotics acts synergistically on after-meal blood fats, with the probiotic replacing Bifidobacteria that berberine suppresses and berberine activating the bacteria's fat-handling genes. They state the limits plainly: only 13 weeks and no heart-attack or stroke outcomes, testing only after a carbohydrate meal, and unknown applicability to people already on statins. The authors propose that probiotics containing Bifidobacterium may be needed when berberine is used as a lipid-lowering agent. They suggest studying fatty meals and other gut-related pathways in future work.

Key findings

• In a 12-week trial of 365 adults with newly diagnosed type 2 diabetes in China, only the combination of berberine (a plant alkaloid from Coptis chinensis) plus a nine-strain probiotic significantly lowered cholesterol measured 2 hours after a carbohydrate meal: total cholesterol fell 24.29 mg/dL versus 8.66 with placebo (adjusted P = .001), and LDL cholesterol fell 16.54 versus 7.35 mg/dL (P = .043).
• Berberine alone and probiotics alone did not differ significantly from placebo for after-meal total or LDL cholesterol (all P values .14 to .91), although after-meal triglycerides fell with berberine alone and with the combination (P = .037 and .035).
• The combination changed 31 blood lipid molecules, versus 8 with berberine alone and 2 with probiotics alone, and higher stool levels of the probiotic bacterium Bifidobacterium breve went with lower after-meal cholesterol.
• In laboratory dishes berberine slowed B. breve growth but increased activity of its four fadD genes (genes for taking up and handling fatty acids), which the authors propose explains why the combination works better than either alone.
• The study followed participants for only about 13 weeks, tested lipids only after a carbohydrate meal, measured no heart-attack or stroke outcomes, and did not report adverse events, so its applicability to people on statins or to fatty meals is unknown.

Common questions