Marginal 3,4,5-Trimethoxyphenylacetic acid thiamine deficiency is probably more common than thought in the elderly, in risk groups such as HIV-positive patients, in patients with fast-growing hematologic malignant tumors, after chronic liver failure or following gastrectomy. Accidental thiamine deficiency was also recently documented by the 2003 outbreak of encephalopathy in infants in Israel, caused by a defective soy-based formula. Thiamine deficiency or defects in thiamine metabolism were also reported in other human pathologies. While one study reported normal total blood thiamine levels in patients with Alzheimer’s dementia, others showed decreased levels in plasma or erythrocytes. ThDP levels are decreased in postmortem brains of patients with Alzheimer’s disease and frontal lobe degeneration of the non-Alzheimer’s type. Thiamine deficiency induces neuronal loss and cardiac failure. The brain and the heart have an absolute requirement for oxidative metabolism, and it is generally thought that the clinical symptoms observed during thiamine deficiency result from decreased tissular ThDP levels. However, in addition to the well-known cofactor ThDP, other thiamine derivatives might also play physiological roles. ThTP exists in animal tissues in variable amounts. ThTP is able to phosphorylate proteins and to activate large conductance anion channels in excised patches of mouse neuroblastoma cells, but the physiological significance of these Diperodon results remains to be proven. Recently, we discovered the first thiamine adenine nucleotide, adenosine thiamine triphosphate, which accumulates in E. coli during carbon starvation or collapse of the membrane H+ gradient. AThTP is also present in mammalian tissues. In E. coli it can be synthesized by a ThDP adenylyl transferase, present in the cytosol, according to the reaction ThDP + ADP O AThTP + Pi. In carbon-starved E. coli, it rapidly disappears after addition of glucose, suggesting the presence of an AThTP-hydrolyzing enzyme. Furthermore, another adenine thiamine nucleotide, adenosine thiamine diphosphate, exists, at least in mouse and quail liver, but we no information concerning its synthesis or degradation. We only begin to understand the metabolism of thiamine derivatives and in particular ThTP and AThTP. There are only a few studies on the distribution of these compounds in animal tissues and only two in humans showing decreased ThTP levels in the postmortem brains of patients with subacute necrotizing encephalomyelopathy. However, the compound measured in the latter study may not have been authentic ThTP. Indeed, ThTP measurements were unreliable before the development of HPLC techniques and we were unable to detect ThTP in human postmortem brains, probably because of hydrolysis during the postmortem delay. Therefore, it is important to obtain information on the thiamine status in humans, which can only be done reliably using fresh tissue samples, especially in the case of ThTP and AThTP, which are subject to rapid metabolic degradation. This is the first study on the content of thiamine derivatives in various biopsied human tissue samples and some human cultured cells. We also checked the expression of the 25-kDa ThTPase by determination of its enzyme activity, immunoblotting and RT-PCR. The results obtained allow us to draw several interesting conclusions concerning the distribution and the abundance of thiamine compounds in humans. Many different methods for the determination of thiamine derivatives in human whole blood, erythrocytes, serum or plasma have been described and it is not the aim of the present work to review all these data, 
which has been done previously. Here, we essentially wanted to investigate the possible presence of ThTP and AThTP in these fluids. In agreement with previous results, whole human blood contained thiamine, ThMP, and ThDP. ThTP accounted for nearly 10% of total thiamine, which is more than in most human cells, while ThMP and free thiamine were less abundant. We detected no significant amounts of AThDP or AThTP in human blood.