Comments on: Benfotiamine Pharmaceutical Therapy May be Alternative to Islets Transplants

By: JPMarat

JPMarat — Wed, 19 Aug 2009 19:50:34 +0000

If high blood sugar per se were so extremely toxic, I doubt that nature would have populated the world with so many animal species lacking a pancreas (such as frogs) or having enormously high blood sugar as a constant, normal state (such as hummingbirds): see J. Hargrove, “Adipose Energy Stores” Nutrition Journal, vol. 4, p. 36 (2005). The fact that patients who have survived 50 years or more with type 1 diabetes have, on average, huge HbA1c levels (greater than 10%), but still seem almost perfectly protected from complications suggests that something more than hyperglycemia is necessary to produce the vascular and neurological changes associated with diabetes: see G. Gill, et al, “Insulin-Dependent Diabetes of over 50 Years’ Duration” Practical Diabetes International, vol. 10, no. 2, p. 60 (2005). Perhaps the highly varied fates diabetic patients have with the same average blood sugar levels indicates that the complications arise from a ‘gunpowder and match’ mechanism, in which hyperglycemia is the gun powder which lies dormant unless the patient has the ‘match’ of the required enzymes in the necessary concentration to process it into harmful AGEs. If so, then since the ‘match’ can be immediately, safely, simply, and inexpensively extinguished by benfotiamine, while the ‘gunpowder’ can only be expensively, elaborately, imperfectly, and sometime in the future neutralized by islet cell encapsulation, some of the research resources now spent on islet cell encapsulation might profitably be devoted first to clinical studies of benfotiamine.

I doubt that this will ever happen, however, since while there is an enormous amount of money to be made in selling diabetics various drugs and devices to bridge the gap between the blood sugar control they can achieve and the control they are told they should achieve, there would be little or no profit in promoting benfotiamine as an unpatentable substitute for these expensive treatments.

By: Scott King

Scott King — Mon, 17 Aug 2009 14:45:28 +0000

If you believe that large doses of benfotiamine would chemically imitate the effect of perfect blood sugar, then your conclusions follow: dosing with a benign and inexpensive pill would be cheaper and more effective than any form of islet transplantation. But I don’t believe that one can chemically simulate the effect of perfect blood sugar in the presence of high blood sugar.

I think there is confusion between the end point and a surrogate end point. Blood sugar itself is not why we fight diabetes. The vascular problems of diabetes are why we try to cure it. Blood sugar is a surrogate end point, and a good one; it is near-universally believed that continuous euglycemia will result in elimination of diabetic vascular disease. Now Brownlee’s theory is that chemical reactions of proteins with sugar form ‘glycated proteins’ which are the cause of the vascular problems. (HbA1c is one such protein). It is the bridge from sugar to vasculature. In his Banting lecture he called it “A Unifying Mechanism.” I don’t think that is right; it is an oversimplification of a chemically and biologically complicated situation. To me it is like saying that HbA1c causes diabetes complications. No, it is just correlated.

Benfotiamine is not the first therapy that Brownlee thought would prevent diabetes complications. (I remember when he first proposed his hypothesis.) The proof would come with clinical results. I am not fully up on the literature, but what I have seen talks about ‘complication-causing pathways’ and ‘therapeutic rationales.’ I want to see actual reduction in, e.g., retinopathy, in human populations. I can’t find it. Does it exist?

I have always been pretty underwhelmed by the Brownlee theory. Certainly for myself I would prefer euglycemia from the Islet Sheet to reduction of complications because with euglycemia you don’t get complications to reduce.