Alzheimer’s disease is an age-related neurodegenerative disease with cognitive dysfunction such as learning and memory as the main clinical manifestation. Recently, Professor Zhong Chunjiu, deputy director of the Department of Neurology, Zhongshan Hospital Affiliated to Fudan University, led members of the scientific research team to discover for the first time that a vitamin B1 derivative, benfotiamine, has a therapeutic effect on Alzheimer’s disease during research on the onset and treatment of Alzheimer’s disease.
Alzheimer’s disease (AD) is a neurodegenerative disease that mostly affects the elderly, with cognitive dysfunction as the main clinical manifestation. To date, the exact pathogenesis of AD remains unclear, and treatments for AD are designed to improve cognitive symptoms but cannot prevent or reverse the disease process. Abnormally elevated blood glucose and diabetes may be independent risk factors for dementia and AD. The glucose and energy metabolism of brain cells in AD patients are significantly reduced, and this is significantly earlier than the formation of clinical symptoms and characteristic pathological damage [1].
After benfotiamine was synthesized in Japan in the 1960s, it began to be gradually used to treat neuropathy, sciatic nerve and other nerve pain caused by alcoholism, and it also has excellent effects in the treatment of diabetic complications. Benfotiamine can regulate glucose metabolism and reduce oxidative stress damage. In animal experiments, benfotiamine can prevent the occurrence of diabetic complications [3]. Schmid et al [4] found that benfotiamine has direct antioxidant effects. At present, benfotiamine has been widely used in the treatment of diabetes complicated with neuropathy, and has a certain therapeutic effect on AD.
The relationship between thiamine and AD
Thiamine is a nutrient necessary to maintain normal metabolism and physiological functions of the body. It exists in the body in the form of thiamine pyrophosphate (TPP) and is a component of various metabolic enzymes in the body such as transketolase (TK), pyruvate Coenzyme of dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KGDH), involved in the oxidative decarboxylation of glucose, pentose phosphate cycle, synthesis of fatty acids, and hydroxylation of steroids. Thiamine can prevent retinal capillary endothelial cell damage caused by hyperglycemia, inhibit glomerular ultrafiltration caused by diabetes, reduce proteinuria production in diabetic rats, reverse blood lipid disorders caused by hyperglycemia, and enhance the contractility of cardiomyocytes. Reduce the apoptosis of vascular endothelial cells and pericytes.
Pharmacological effects of benfotiamine
Anti-Alzheimer’s Effect
Although thiamine deficiency is closely related to AD, clinical studies have confirmed that thiamine cannot change the progression of AD patients. After oral administration of benfotiamine, a fat-soluble derivative of thiamine, the concentration of thiamine in plasma and tissue was higher than that after administration of equal doses of thiamine and its water-soluble derivatives. Benfotiamine has the effect of improving cognitive function and reducing Aβ deposition in AD mice. Its mechanism of action has nothing to do with thiamine. It is likely to act by increasing the phosphorylation levels of glycogen synthase kinase-3α and 3β. It is suggested that the development of benfotiamine for the treatment of AD has good prospects.
Protective effect on diabetic complications
More and more studies have shown that benfotiamine reduces the complications of diabetes (such as neuropathy, nephropathy, and retinopathy) by inhibiting the formation of advanced glycation end products (AGE). Benfotiamine can increase TPP in tissues, which can enhance the activity of transketolase to reduce AGE in tissues, ultimately inhibiting the development of diabetic complications. The effects of benfotiamine also include improving diabetic myocardial contractile function, reducing neuropathic pain, and improving post-ischemic ventricular dysfunction.
Pharmacokinetic characteristics of benfotiamine
Benfotiamine is a fat-soluble derivative of thiamine. Its unique open thiazole ring structure allows it to directly penetrate the cell membrane, thereby significantly improving bioavailability. Compared with water-soluble thiamine, oral fat-soluble benfotiamine has better absorption and bioavailability, and its plasma concentration is at least 5 times that of an equivalent dose of water-soluble thiamine. After oral administration of benfotiamine, it is first dephosphorylated to S-benzoylthiamine (SBT) by alkaline phosphatase in the gastrointestinal tract, and the fat-soluble SB poloxamer 188T enters the intestine under passive diffusion. membranes and endothelial cell membranes, and subsequently enter the systemic circulation. A large portion of SBT enters red blood cells and is converted into thiamine.
