This is a followup thread to the thread here: http://www.longecity...icity-concerns/
I did follow up some of the research on that thread and found that the dosages that resulted in cancer in 2 years fed rats are right in the therapeutic range being consumed by berberine users for a metformin replacement.
I'm not a researcher and don't have any real sense of how meaningful the work was. However, it was not followed up and I think it should be and using berberine instead of goldenseal. What follows is a letter I've sent to various researchers and other interested parties. I've had no response at all which could mean that no one wants to get their hands dirty, that there is something seriously wrong with the research or any other number of reasons.
I think what I've written below is pretty clear and indicative of a real possibility that berberine may be a lot more dangerous that assumed by most who are taking it. Positive press abounds but these articles and a few others raise significant doubts. I know I won't be taking it any more.
I'd like to hear comments especially from those familiar with the types of in vivo studies done by the National Toxicology Project and how meaningful the 20%+ liver carcinoma/adenoma rate is as an indicator that at the very least more research should be done.
I'd also like to hear suggestions about how to make it happen.
Here then is the latest version of the letter I've been sending out with links to the research and the salient points.
Dear ______
I would like to call your attention to some in vivo studies done with rats and mice to determine if Goldenseal is a carcinogen. The work was done by The National Toxicology Program. They did find goldenseal to be a possible carcinogen. More importantly their research and subsequent research strongly suggest that the alkaloid berberine is the most likely cause of cancer found in 2 year old rats.
Of even more significance is the fact that the rat dose where the cancer occurred when converted to a human equivalent dose (8.8mg/kg) is right in the range of what many diabetics are taking in lieu of Metformin. If the research is truly indicative of the carcinogenicity of berberine we may be facing a significant rate of liver cancer in T2D sufferers.
I have called the attention of several doctors and alternative health practitioners to these findings by posting on their blogs and writing to their contact addresses but have received no response positive or negative. I wrote to the corresponding author, Dr. June Dunnick at the NTP and she suggested requesting a trial at the NTP/NIH website which I intend to do.
What I would really like is to find a lab willing to undertake a 2 year study of berberine preferably with short term to full term sacrifices of the experimental animals to assess progress of tissue changes, if indeed there are any, and hopefully using rats with human tissue to eliminate as much doubt as possible. Any help or suggestions from you as to how to go about making this happen or resources would be highly appreciated.
Here is a summary of what I have found:
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 concentration and somewhat weaker than that of berberine.
That paper is here:http://www.sciencedirect.com/science/article/pii/S0378427413008412
As I said the NTP of the NIH actually ran 3 different trials. A paper containing all the work is here:
http://ntp.niehs.nih..._rpts/tr562.pdf (190 pp)
There is a summary of the long report immediately above here:
http://ntp.niehs.nih...r562/index.html
Here are my dosage calculations taken from a forum post:
The weight to weight mg/kg ratio is designed to eliminate the need to take into account the individual weight of the differing subjects. When the number of 54.6 mg/kg (from the research) is cited it means that the animal is consuming his own weight * that amount in berberine as a constituent of the total Goldenseal added to the diet which is 3.9% of the total Goldenseal. If the rat weighed 1kg it would have consumed 54.6mg if it weighed 0.1 kg it would have consumed 0.1 * 54.6mg or 05.46mg.
Now let’s move to humans. If we had a 1 kg human being they would consume exactly the same as a 1 kg rat or 54.6mg. If we had a 100kg human they would consume 100*54.6mg or 5460mg.
However, because animals have different consumption rates depending on volume:weight ratios experimenters adjust dosages according to those ratios. For rat:human that ratio is 6.2:1 meaning a rat has to consume 6.2 times as much as a human per kg of weight to get the same effect from a drug. Therefore to get the human EQUIVALENT dose the rat dose is divided by 6.2. 5460mg/6.2 = 880mg or slightly less than 2 500mg caps for a 100kg human. 100kg=220pounds.
Clearly this dose of 880mg is well within what is considered “therapeutic” by the manufacturers and consumers of berberine.
