August 14, 2013

Berberine Works But May Very Well Be Harmful

I have been getting a lot of email of late about the supplement Berberine, which appears to be the latest miracle cure being sold to those people with diabetes who believe that completely unregulated herbs imported from countries with long histories of food and drug adulteration are somehow safer and "more natural" than the tightly regulated pharamceuticals.

Berberine does appear to work to lower blood sugar. The problem is that we really know very little about how it does it or what its long term effects are on the body.  I see many mentions on sites promoting berberine supplements of the fact that berberine has a long history of use in Chinese medicine. However, quite a few of the traditional Chinese herbs have turned out to be highly toxic, and it's worth noting that the incidence of kidney and other urinary tract cancer among Chinese herbalists is far greater than that of the population at large. (Details HERE)

You can lower blood sugar by damaging your liver as happens with severe alcoholism.  You can lower blood sugar with drugs that raise the likelihood of heart attack, as is the case with most sulfonylurea drugs. (Details HERE) You can lower blood sugar with drugs that over time damage the pancreas as is the case with the incretin drugs.(Details HERE)  And you can lower blood sugar by taking drugs that turn bone precursor cells into fat cell, as happens with Avandia and Actos, which, over a decade of use of these drugs can lead to your developing bones so brittle that they are prone to breaking. (Details HERE)

Many of these severe, life-ruining side effects did not show up until people had taken these drugs for five to ten years. So the fact that a drug lowers blood sugar for three months in a small population without major harm tells you nothing about its actual safety.

To get a feel for the quality of the research supporting the claims about berberine, scroll down to the Reference section of this page: .

Ignore the enthusiastic editorializing by the editors of the site who don't know very much about diabetes or the drugs that berberine is being compared to and pay attention to the quality of the journals publishing these studies. Most are very obscure. Some sound like they are one of the many  "pay to play" journals beloved by supplement sellers--journals that will publish anything as long as they are paid a hefty fee.

Those studies on berberine published in respected endocrinology journals involve small groups of people taking the drug for very short periods. The only one I could find with a large number of subjects is a meta analysis where data from 14 different very small studies was pooled. Meta analyses are only as good as the quality of the underlying studies, which in this case is not very good.

Some studies published in quality journals suggest that berberine's positive effects may stem from the fact that it activates AMP-Kinase, which is what metformin does. If this is the case, you have to ask yourself, why not just take metformin, a safe, very well understood drug that has been in use since the 1950s and which must meet rigorous manufacturing standards before it is sold.

Several mainstream studies claims to have found that berberine inhibits DPP-4 and raises the concentration of the incretin hormone GLP-1 which is the mechanism used by the incretin drugs Januvia,  Onglyza, and Trajenta. As discussed elsewhere, inhibiting DPP-4 can turn off a mechanism the immune system uses to kill cells that have become cancerous, which may make these a poor choice of drug. In addition, accumulating evidence is pointing to the possibility that artificially raising GLP-1 levels over a long period of time leads to the growth of abnormal cells in the pancreas which may grow into the ducts and cause pancreatitis or turn into precancerous tumors.  (Details HERE)

Mainstream research also finds that berberine has a significant impact on your liver. Repeated use downregulates several important enzymes (P450 cytochromes ) that the body uses to eliminate drugs. You can read about that here:

This means that if you are taking berberine, other drugs you take may not be eliminated properly if they use those enzymes and may build up to toxic levels, while others, which require those enzymes to be working so that the drug can be broken down into the active form of the chemical they contain may not work as expected.

In particular you should not combine repaglinide (Prandin) with berberine as that combination may produce hypos since repaglinide is eliminated from the body by an enzyme that berberine inhibits. Since metformin also inhibits one of these enzymes to some extent, combining berberine and metformin is probably a bad idea, too. (Note I have blogged about the combined effect of metformin and prandin HERE).

Other drugs affected by berberine include cyclosporin (Neoral, Sandimmune), lovastatin (Mevacor), clarithromycin (Biaxin), indinavir (Crixivan), sildenafil (Viagra), triazolam (Halcion), and many others.

As always, when you buy an unregulated supplement, you have no way of knowing what is actually in the pill. Herbs grown in third world countries often contain toxic herbicides which are prohibited in the U.S.. And supplements manufactured abroad may also contain lead and other toxic heavy metals, as well as other contaminants. As supplements are completely unregulated in the U.S. and receive no scrutiny unless they kill someone, the assurances of the supplement companies that their supplements are "pure" are worthless. When supplements are taken to the lab by consumer groups, they often turn out to contain different dosages thatn what the label claims and to be contaminated.

With all this in mind, it seems prudent if you are going to use a drug to lower your blood sugar, to stick to drugs that are regulated, provided in pills of known dosage, and which have long track records for safety. Currently, the only drugs that fit that description are: metformin, insulin, prandin, gliclazide (not available in the U.S.)  and acarbose.