The multifaceted therapeutic potential of benfotiamine

Abstract

Thiamine, known as vitamin B₁, plays an essential role in energy metabolism. Benfotiamine (S-benzoylthiamine O-monophoshate) is a synthetic S-acyl derivative of thiamine. Once absorbed, benfotiamine is dephosphorylated by ecto-alkaline phosphatase to lipid-soluble S-benzoylthiamine. Transketolase is an enzyme that directs the precursors of advanced glycation end products (AGEs) to pentose phosphate pathway. Benfotiamine administration increases the levels of intracellular thiamine diphosphate, a cofactor necessary for the activation transketolase, resulting in the reduction of tissue level of AGEs. The elevated level of AGEs has been implicated in the induction and progression of diabetes-associated complications. Chronic hyperglycemia accelerates the reaction between glucose and proteins leading to the formation of AGEs, which form irreversible cross-links with many macromolecules such as collagen. In diabetes, AGEs accumulate in tissues at an accelerated rate. Experimental studies have elucidated that binding of AGEs to their specific receptors (RAGE) activates mainly monocytes and endothelial cells and consequently induces various inflammatory events. Moreover, AGEs exaggerate the status of oxidative stress in diabetes that may additionally contribute to functional changes in vascular tone control observed in diabetes. The anti-AGE property of benfotiamine certainly makes it effective for the treatment of diabetic neuropathy, nephropathy and retinopathy. Interestingly, few recent studies demonstrated additional non-AGE-dependent pharmacological actions of benfotiamine. The present review critically analyzed the multifaceted therapeutic potential of benfotiamine.

Introduction

Nutritional deficiency is considered to be a major health burden affecting the routine life style of human beings in developing countries. Thiamine is a water-soluble vitamin found mainly in cereals, legumes, dried beans, soybeans, nuts, fortified breads, and lean meats and fish. Thiamine plays a key role in cellular energy metabolism as it helps in the process of conversion of carbohydrates into energy. Thiamine is required for normal functioning of the heart, muscles and nerves, and its intake is beneficial in the treatment of certain metabolic disorders [1], [2]. Benfotiamine is a lipid-soluble thiamine precursor having much higher bioavailability than genuine thiamine [3], [4]. Growing body of evidence revealed that benfotiamine alleviates the severity of diabetic complications such as neuropathy, nephropathy and retinopathy by inhibiting the formation of advanced glycation end products (AGEs) [3], [5], [6]. Benfotiamine prevents the progression of diabetic complications by increasing tissue levels of thiamine diphosphate, which enhances the transketolase activity that directs the precursors of AGEs to pentose phosphate pathway, resulting in the reduction of tissue levels of AGEs [7], [8], [9], [10]. Other beneficial effects of benfotiamine include improvement in cardiomyocyte contractile dysfunction in experimental diabetes mellitus [11], reduction in neuropathic pain [12], [13], [14] and improvement in experimental post-ischaemic healing [15]. Moreover, benfotiamine has been shown to reduce oxidative stress in a mechanism unrelated to its anti-AGE property [4]. In addition to its beneficial effects in preventing the progression of diabetic complications, benfotiamine has been demonstrated to prevent the induction of vascular endothelial dysfunction [9], [16], [17], [18], [19], which suggests the novel role of benfotiamine in improving the vascular functional regulation. Benfotiamine is absorbed in the body better than thiamine and in fact benfotiamine has better bioavailability than thiamine. Although benfotiamine has been shown to be similar to thiamine in correcting endothelial cell defects induced by high glucose [16], thiamine is needed to be administered at high dose as compared to benfotiamine to prevent the diabetic complications [8]. The present review critically discussed the wide array of recently revealed therapeutic potential of benfotiamine.