Benefits of Thiamin (Vitamin B1) Administration in Neurodegenerative Diseases May Be Due to Both the Coenzyme and Non-coenzyme Roles of Thiamin

Although no systematic studies on therapeutic value of thiamin administration in neurodegenerative diseases are available to draw statistically significant conclusion, beneficial effects of thiamin in the diseases have been observed in independent case reports. The data are usually interpreted as improvement of central metabolism due to the coenzyme role of thiamin diphosphate (ThDP) in the transketolase, pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase reactions. However, several lines of evidence support a view that the thiamin action is not limited to this mechanism. First, no firm correlation between the benefits of thiamin administration and levels of ThDP and/or ThDP-dependent enzymes in brain has been shown. Second, synthesis of non-coenzyme derivatives of thiamin, such as thiamin triphosphate and its adenylated form, occurs in nature from bacteria to mammals. Third, emerging data suggest significance of the non-coenzyme derivatives of thiamin for cellular responses to metabolic stress and DNA damage. The review draws attention to importance of these new data for interpreting molecular mechanisms of the consequences of thiamine deficiency or supplementation.