Evidence for Carcinogenicity of Berberine

I’ve found some interesting information/research on goldenseal and its predominant and most active alkaloid berberine. It looks to me like there is a significant danger of carcinoma/adenoma in the commonly used dosage range of berberine for hyperglycemia.

Let me summarize first. In the 2010/2011 timeframe a long term 2 year rat/mouse study was undertaken by the National Toxicology Program at NIH. They ran 2 week, 3 month and 2 year studies. Liver cell hypertrophy was found in both the 2 week and 3 month trials but the 2 year trials showed even more significant damage.

In the two year study male rats fed 25,000 ppm of goldenseal powder ad libitum showed a 20+% incidence of liver hepatocellular adenoma or carcinoma. This was the most significant effect. The concentration of berberine in the goldenseal powder was 3.9% by weight. When all the calculations of converting the amounts taken daily by the rats to a human equivalent dose are done it turns out that the rats with the 20% rate of carcinoma/adenoma were consuming the equivalent of a 100 kg human consuming @880mg/day of berberine. 

Interestingly there was no carcinoma in the female rats and only 2 with hepatocellular adenoma.

Jumping from goldenseal powder to berberine as the culprit is a big jump but reading the paper you will see that the researchers, even though avoiding saying it was definitively berberine that was the cause, did talk a lot about berberine in the discussion.
That first paper is here:http://tpx.sagepub.com/content/39/2/398.long

Subsequent to the paper and motivated by it a second in vitro study was done to try to ascertain how that cancer in the rats might have been caused. In that study the researchers examined 5 alkaloids from goldenseal and found two that were active. Both were topoisomerase I and II interruptors and the researchers felt that this may have been the cause of the cancer in the first experiment. One of those alkaloids palmatine was of much lower...