The connections between thiamine deficiency and the development of fatal conditions such as beriberi, a syndrome compromising the PNS by polyneuritis and/or cardiovascular symptoms, and the neuropsychiatric Wernicke‐Korsakoff syndrome, characterized by encephalopathy and psychosis, were already recognized in the early to mid‐20th century. Vitamin B1, also known as thiamine, has long been known to be associated with functions in the nervous system. We also provide an overview of possible biochemical synergies between these neurotropic vitamins and discuss major roles by which they may contribute to this synergy. 16, 17, 18, 19 The present review aims to compile the most important biochemical pathways of the B vitamins, focusing on thiamine, pyridoxine, and cobalamin, and link them with neurological functions and symptoms related to deficiencies. 2, 14, 15 Indeed, several reports indicate that the specific supplementation with the combination of vitamins B1, B6, and B12 interacts synergistically to improve neuropathy, motor control, nociceptive, and neuropathic pain. 2, 6, 8, 9, 12, 13 However, the significance of these vitamins is also emphasized by the fact that they can improve certain neurological conditions even if no (definite) deficiency can be proven. The importance of B vitamins in the context of nerve function is highlighted by the numerous neurological diseases, such as Wernicke's encephalopathy, depression, beriberi, seizures, subacute combined degeneration of the spinal cord, or peripheral neuropathy (PN), that are related to a deficiency in one or more of these neurotropic B vitamins. 9, 10, 11 Evidence suggests that a significant proportion of the population suffers from deficiencies and insufficiencies of one or more of these neurotropic B vitamins. 2, 9 Indeed, a significant association between cognitive impairment and methionine‐homocysteine cycle dysfunction indicated by low levels of vitamins B6 and B12 has been found. 2, 8 Interaction between pyridoxine and cobalamin in the methionine cycle, as well as their participation in the citric acid cycle with other B vitamins, including thiamine, suggests that these three vitamins are linked from a biochemical point of view. 7 In particular, vitamin B1, B6, and B12 are essential for maintaining the health of the nervous system. It is well known that the diet and thus the supply of nutrients strongly affect normal functioning of CNS and PNS. 1 These commonly called “neurotropic” B vitamins play special and essential roles both in the central nervous system (CNS) and the peripheral nervous system (PNS). 2, 3 Some of the B vitamins do not only contribute to important physiological functions in the whole human body but also possess neurospecific functions. 2, 6 In order to fulfill the coenzymatic function, the biologically active form of the respective vitamin (coenzyme) needs to bind to a corresponding protein (enzyme), thereby activating its enzyme function, so that the cellular processes can take place with the help of the newly formed holoenzyme complex. 1, 5 Although those roles differ, they are closely inter‐related and complement each other. 2, 3, 4 All B vitamins play crucial roles as coenzymes for enzymatic reactions in different biological systems. However, the vitamin B12 produced by bacteria in the colon of humans is not available for uptake because adsorption only takes place further up in the ileal mucosa through an intrinsic factor‐mediated mechanism. Only vitamin B12 is not produced by plants but by bacteria that colonize the foregut of ruminants or the colon of humans and thus can only be found in animal products like liver, fish, eggs, or dairy products. Even though most of them are produced by plants, they can be ingested indirectly via animal‐derived food like meat, dairy, and eggs. Mammals are not able to synthesize B vitamins on their own therefore, they must take them up in sufficient quantities with the diet. 1, 2, 3 Even though they are biochemically not related, referring to them as a group makes sense because they often naturally occur in the same foods 1 and share the feature of being water‐soluble. The eight B vitamins B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B7 (biotin), B9 (folate), and B12 (cobalamin) form a group of chemically very heterogeneous essential substances, which have a wide variety of functions in the human body.
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