American Journal of Clinical Nutrition, Vol 20, 528-542, Copyright © 1967 by The American Society for Clinical Nutrition, Inc.

Biochemical Alterations in Thiamine Deficiency—Their Interpretation

¹ From U.S. Army Medical Research and Nutrition Laboratory, Fitzsimons General Hospital, Denver, Colorado

In evaluating thiamine nutritional states, it would appear justified to determine, whenever feasible, not only thiamine excretion in the urine, but also erythrocyte transketolase activity. Determination of an appropriate thiamine-dependent enzyme system reflects the metabolism of the vitamin at the cellular and molecular level. Urinary thiamine levels can provide information as to the adequacy of the dietary intakes, but do not necessarily evaluate accurately a marginal deficiency. Determinatons for pyruvic acid and other metabolites in blood or urine can provide evidence of a thiamine insufficiency, particularly when clinical signs are evident. Determinations of free thiamine in plasma do not necessarily reflect a direct relationship to the level in the blood and tissues. Erythrocyte or leukocyte thiamine values apparently show a more direct relationship to tissue content. It is for this reason that erythrocyte transketolase activity appears to provide information as to tissue reserves of thiamine and reflects a direct functional evaluation at the cellular level. Consequently, the transketolase activity assay makes it possible to differentiate with reasonable accuracy between hypovitaminosis and a sufficient thiamine intake, as well as between hypovitaminosis and avitaminosis thiamine.

Biochemical changes may precede clinical manifestations of a disease situation. Such changes may have prognostic value. Other biochemical changes, such as lowered urine or plasma levels of thiamine may indicate only low nutrient intakes and not reflect any metabolic abnormalities. However, plasma or urine thiamine levels of a certain critical level, if continued without increased dietary intakes and concomitant plasma or urinary increases, would lead to metabolic abnormalities detected by other biochemical means. Clinical manifestations may still not occur at this state of the deficiency. In other instances, biochemical changes occur simultaneously with clinical manifestations. Such tests perhaps could be improved in sensitivity in order to detect earlier existence of deficiency alterations. However, even so, such tests can corroborate a tentative clinical diagnosis.

Not all biochemical tests that may be developed for the clinical laboratory can be used for nutritional survey work, for numerous reasons, including technical, physical, and economical. Nevertheless, an attempt should be made to devise methods that may receive as broad an application and use as possible. Undoubtedly, the transketolase activity assay procedure could be developed into a more routine test with further study. In certain instances, particularly where endemic vitamin B₁ deficiency occurs, physical performance and mental performance evaluations need to be incorporated into the biochemical tests in an attempt to enhance the sensitivity and specificity of the methods. Early detection by biochemical means appears essential in infantile beriberi in order to employ corrective measures before death ensues.