Subclinical protein malnutrition is a determinant of hyperhomocysteinemia

Hyperhomocysteinemia is regarded as a public health problem of increasing importance likely to contribute to vascular disorders and premature mortality. Folate, cobalamin, pyridoxine, and riboflavin dietary deficiencies are currently regarded as causative factors. However, several investigations have indicated that the theory of vitamin B deprivation provides only a partial explanation for the observed abnormalities of sulfur-containing amino acids. We investigated the potential contributory role played by protein malnutrition.

For that purpose, three cohorts of 20 adult patients presenting stage I, II, and III goiter underwent careful medical history, dietary inquiry, and clinical examination. Their overall health and nutrition states were assessed with classic anthropometry, measurement of vitamin B blood parameters, visceral protein markers, essential amino acids, total homocysteine, and cystathionine.

The concentrations of transthyretin, seven essential amino acids, and cystathionine progressively decreased as the thyroid gland increased. Methionine was the sole essential amino acid whose values did not change; total homocysteine was unique in that increased levels correlated negatively with transthyretin values. Taken together, the data point to a progressive deterioration of protein nutrition status impairing the transsulfuration pathway and is best explained by an acquired defect of cystathionine-beta-synthase activity.

Hyperhomocysteinemia may arise from the shrinking of endogenous nitrogen pools as a result of decreased protein intake or stress-induced increased losses. Raised total homocysteine may result from the attempt of the malnourished and/or stressed body to preserve methionine homeostasis.