The excursions of glucose in the blood of a person living with diabetes wreak havoc on various tissues over the long term. Prolonged and sustained elevations in blood glucose can result in ?glucose toxicity,? believed to result in the accelerated formation of modified, long-lived proteins called Advanced Glycation End products (AGEs). These products exert their effects through their cognate receptor, appropriately named RAGE. AGEs contribute to the oxidative, inflammatory and vascular stress associated with complications of the disease. AGEs also are formed during the high heat exposure of foodstuffs containing sugars, proteins and fats.
Recent preliminary research indicates that energy (calorie) and total and saturated fat intakes are positively correlated with dietary intakes of AGEs.1 Various drug development efforts have been directed at mitigating the ravage of RAGE and AGEs. One molecule that has been pursued is thiamine, otherwise known as vitamin B1, which is water soluble.
Vitamin B1 has a prominent role in glucose metabolism, perhaps of pivotal importance in the diabetic state. Some evidence indicates that diabetics are ?biochemically? compromised in relation to B1 status, displaying reduced activity of a B1-dependent enzyme (transketolase) within red blood cells.2 Such a compromise may prevent this B1-dependent enzyme from relieving the metabolic stress of diabetes, the latter of which drives the hyperaccumulation of specific molecules that now undergo a pathogenic transition.
These side reactions yield various downstream metabolites that can effect adverse changes in blood vessels and cellular architecture. High-dose supplementation with vitamin B1 has very recently been shown to prevent the development of diabetic kidney disease (nephropathy) in an animal model of (toxin-induced) diabetes.3
In this study, normal rats and those rendered insulin-dependent diabetic were fed a controlled diet providing 25.7mg B1/kg, about six-fold greater than the recommended daily allowance for adult rats, or one enriched with 7mg or 70mg/kg B1, for 24 weeks. All diabetic animals were also given moderate-dose insulin therapy. No significant changes in blood glucose or hemoglobin A1c (an AGEs-modified form of hemoglobin) were seen in the diabetic groups receiving B1-enriched diets. This animal model inevitably leads to the development of kidney dysfunction, nephropathy, over 24 weeks. However, in both thiamine groups kidney dysfunction, as measured by the presence of the serum proteins in the urine, was arrested by 70 to 80 per cent. (The healthy kidney typically prevents the filtration of blood proteins into the urine, because of their large molecular size.) The production of AGEs was also substantially reduced by B1.
The authors concluded by advocating the consideration of B1 as therapy to prevent diabetic nephropathy in humans.
An additional series of groups in this study received a liposoluble derivative of B1, S-benzoylthiamine monophosphate (SBT), with similar results be-ing obtained. Additional studies with SBT have shown prevention of diabetic retinopathy, a disease affecting the retina and evolving from damage to the tiny blood vessels in the eye.4
Collectively, these studies lend compelling support to the premise of high-dose thiamine and its derivatives as both prophylactic and therapeutic strategies against the rage of diabetes and its inevitable complications. It also encourages the pursuit of modified-delivery vehicles for B1, which would approach the superior bioavailability of SBT.5
Anthony Almada, MSc, is the president and chief scientific officer of IMAGINutrition Inc and has been a co-investigator on more than 60 randomised controlled trials. www.imaginutrition.com
Respond: [email protected]
1. Goldberg T, et al. Evaluation of daily consumption of advanced glycoxidation end-products in healthy and diabetic type 2 subjects. Diabetes 2003;52 (Suppl. 1):A554.
2. Saito N, et al. Blood thiamine levels in outpatients with diabetes mellitus. J Nutr Sci Vitaminol 1987;33:421-30.
3. Roya BJ, et al. Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine. Diabetes 2003;52:2110?20.
4. Hammes HP, et al. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nature Med 2003;9:294-9.
5. Bitsch R, et al. Bioavailability assessment of the lipophile benfotiamine compared to a water-soluble thiamine derivative. Hum Nutr Metab 1991;35:292-6.