Efficacy of benfotiamine versus thiamine on function and glycation products of peripheral nerves in diabetic rats

Abstract

In rats with streptozotocin (STZ) induced diabetes the effect of (watersoluble) thiamine nitrate and of (lipidsoluble) benfotiamine on peripheral nerve function (motor nerve conduction velocity) as well as on the formation of advanced glycation end-products in peripheral nerve tissue was studied. In one group of animals drug administration was started immediately after diabetes induction (prevention study) and in another group two months after diabetes induction (treatment study). Motor nerve conduction velocity (NCV) dropped by 10.5% in diabetic animals, carboxymethyl-lysine (CML) rose to a 3.5fold concentration, deoxyglucosone (3DG)-type AGE formation was increased 5.1fold compared with controls. After three months preventive administration of both vitamin B(1) preparations NCV had increased substantially compared with results in diabetic controls. It was nearly normal after six months with benfotiamine, while the administration of thiamine nitrate resulted in no further amelioration. NCV was nearly normalized after six months of benfotiamine application but not with thiamine. Furthermore, benfotiamine induced a major inhibition of neural imidazole-type AGE formation and completely prevented diabetes induced glycoxidation products (CML). Treatment with thiamine did not significantly affect AGE or cmL levels. Unlike treatment with water-soluble thiamine nitrate timely administration of liposoluble prodrug benfotiamine was effective in the prevention of functional damage and of AGE and cmL formation in nerves of diabetic rats.

High-dose thiamine therapy counters dyslipidaemia in streptozotocin-induced diabetic rats

“…There was no improvement of glycaemic control in STZ diabetic rats by high-dose thiamine or benfotiamine therapy in this study, as found in independent investigations [16,17]. Thiamine therapy has been shown to decrease hyperglycaemia in cirrhosis [18], where hyperglycaemia is linked to insulin resistance of muscle and inadequate insulin secretion by beta cells [19], and in thiamine-responsive megaloblastic anaemia (due to mutated high-affinity thiamine transporter), where hyperglycaemia is linked to impaired insulin secretion [20].…”

“…Thiamine and benfotiamine also suppressed the development of diabetic neuropathy and benfotiamine suppressed the development of retinopathy (where thiamine was not evaluated) in experimental diabetes in vivo [16,17]. It is not known if high-dose therapy of thiamine or benfotiamine will be effective against microvascular complications, dyslipidaemia and cardiovascular disease in clinical diabetes.…”

Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes

“…Independent MS estimates of CML residues of renal glomeruli [22] and immunoassay of CML content of plasma protein of healthy control rats [23] were in agreement with estimates herein. Immunoassay of AGEs in tissue, however, has overestimated increases in experimental diabetes [4,5,24].…”

“…This counters multiple pathways of biochemical dysfunction linked to the development of vascular complications with doses of the vitamin markedly higher than the dietary reference intake [2]. High-dose therapy with thiamine and the thiamine monophosphate (TMP) derivative benfotiamine prevented the development of microvascular complications in experimental diabetes [3][4][5]. A pilot-scale trial of type 2 diabetic patients with incipient nephropathy (microalbuminuria) showed that high-dose thiamine therapy improved renal function and induced regression of microalbuminuria [6,7].…”

Efficient Transdermal Delivery of Benfotiamine in an Animal Model

“…Benfotiamine, (S-benzoylthiamine-Omonophosphate), a derivative of the vitamin B1 or thiamine, has a much higher bioavailability than thiamine and, as a result, accumulates in the target tissues much more than thiamine itself [15,19,20]. Thiamine absorption from oral benfotiamine is approximately five times greater than from conventional thiamine supplements [21][22][23].…”