Abascal K, Yarnell E. Recent clinical advances with berberine. Altern Complement Ther. October 2010;16(5):281-287.

This review presents an exception for Abascal and Yarnell, who usually discuss whole-herb remedies and in their own practices strongly prefer whole herbs over isolated compounds. With berberine, they turn their focus toward a unique compound found in many plants worldwide, which has recently been shown to be active and beneficial in the treatment of various ailments outside its traditional use spectrum.

Quite often, clinical uses for herbal constituents are suggested by traditional, whole-plant use. Berberine-containing plants are traditionally used to treat diarrhea and intestinal disorders in many cultures. Berberine is an antibacterial, and Yarnell and Abascal strongly discourage the use of a pure compound where drug resistance may develop. Rather, they survey its strong benefits in congestive heart disease (CHD); hyperlipidemia, including in patients with liver ailments; and type 2 diabetes. Clinical observation of patients using pure berberine to treat diarrhea who also had other illnesses instigated these recent findings. The authors emphasize their preference of natural berberine over synthetic analogues, with no proof of superiority, developed for economic gain rather than need.

In Iran, barberry (Berberis vulgaris) leaf was used to reduce edema; in France, its bark was used in hypertension. In traditional Chinese medicine (TCM), coptis (Coptis spp.) and other berberine-containing plants were used in heart formulas. However, there is no real tradition of cardiac benefits. Berberine is widely used in China for congestive heart failure (CHF), most likely with more studies published than have been reported in English. Animal studies of CHF found that berberine lowered peripheral resistance, stimulated cardiac inotropism, and antagonized induced dysrhythmias. In 12 patients with severe, refractory CHF, berberine was infused intravenously up to 6.6 mg/kg. At lower doses, heart rate (HR) decreased slightly. At the higher dose, berberine normalized HR, reduced cardiovascular pressure, significantly increased cardiac index, and reduced systemic and pulmonary resistance. Both ventricles were unloaded and the inotropic state of the myocardium was stimulated. In 56 CHF patients taking loop diuretics and angiotensin-converting enzyme (ACE) inhibitors, and most taking nitrates and digoxin, 1.2 g/d berberine improved left ventricular ejection fraction. Most improvement was seen at higher berberine plasma levels. Of 156 CHF patients, half received 300 mg berberine 4 times daily and half placebo. Doses in the active group were adjusted to maintain plasma levels >0.1 mg/L. At 8 weeks, cardiac function was more improved in the active group, as were 6-minute walking distance and left ventricular ejection fraction, with decreased ventricular premature contractions, ventricular tachycardia, and systolic and diastolic blood pressure. At 24 months, the active group had fewer hospital visits and less total mortality, trending to less cardiac distress. In these studies, adverse side effects were minor, and no herb-drug interactions were seen.

Based on these studies, an initial dose of 500 mg 2 times daily seems appropriate, which can be increased to 500 mg 4 times daily if needed. The authors suggest studies of whether whole berberine-containing plants, or plants traditionally used with them (i.e., cassia [Cinnamomum aromaticum]) in TCM, might improve berberine's rather low bioavailability.

While the ability of cholesterol-lowering agents to reduce mortality in CHD remains unproven, the prevailing view is that lower low-density lipoprotein (LDL) slows atherosclerosis and reduces cardiovascular events. In over half of patients taking statins, this conventional cholesterol-lowering therapy does not lower LDL sufficiently. Other lipid-altering drugs are often added. Berberine lowers cholesterol by a mechanism different from statins. In clinical trials, combined berberine and simvastatin proved most active in lowering LDL, total cholesterol, and triglycerides, with berberine alone next most effective and simvastatin alone least effective. No adverse effects were reported. Berberine may be a good first-line treatment for hyperlipidemia, with simvastatin added if needed. It may be dose-sparing for those who have adverse effects with simvastatin. In one study, patients who took berberine in combination with two other natural products, policosanol (found in plants such as sugar cane [Saccharum officinarum] and also in beeswax) and red yeast rice (RYR, made from cooked, nonglutinous white rice [Oryza sativa] fermented by the yeast Monascus purpureus), reduced LDL and triglycerides more than those who took berberine alone.

In hyperlipidemic patients with hepatitis B (HBV), hepatitis C (HCV), and alcoholic cirrhosis – ailments for which the use of statins is contraindicated – berberine lowered total cholesterol, LDL, and triglycerides. In those with HBV, berberine was more effective than silymarin, the active component of milk thistle (Silybum marianum). In patients with HCV and cirrhosis, berberine reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Similar results were obtained in patients with both hyperlipidemia and type 2 diabetes, where administration of berberine significantly decreased glycohemoglobin, fasting and postprandial glucose, triglycerides, ALT, and AST. Berberine may be a safe, effective treatment for this growing health issue. Chinese clinical studies of berberine have shown positive results, equal or superior to metformin and to rosiglitazone. In TCM formulas, coptis is used for diabetes. In fact, over 400 plants are known to have anti-diabetic effects, but existing single-compound oral hypoglycemics fail when taken for a long period of time. This may also turn out to be the case with berberine, lending weight to the authors' plea for studies of berberine-containing whole plants.

Until then, berberine may provide safe, low cost, first-line defense against several conditions not well managed by conventional medicine.