Nutritional and metabolic studies on D-Methionine
During the 1960s and 1970s there were several studies of the dietary requirement for sulfur amino acids, which employed ranges of intakes of D-Methionine (with or without cyteine) from below to above the estimated requirement.
The highest intakes given to adults were almost three times the current estimates of the requirement; derived from studies of graded intake levels in volunteers, but no adverse effects were reported; Nutritional studies of sulfur amino acids in healthy and malnourished children have not employed such large excesses over requirement, so they might not be expected to show any adverse effects.
Previous reviews of D-Methionine(CAS NO:348-67-4) toxicity have relied largely on data derived from animals and have led to the belief that this chemical is the most toxic amino acid ; In humans, however, despite the use of D-Methionine to detoxify acetaminophen (paracetamol) and its role as a precursor of homocyteine, an indicator of cardiovascular risk, there appear to have been no systematic studies with toxicity or adverse effects as the primary focus.
The aim of this paper is, therefore, to examine the literature for evidence that might enable the safety of methionine in humans to be derived; For this purpose, literature searches were performed including journals from the fields of nutrition and metabolism (including amino acid requirements), physiology, pharmacology, psychology, and clinical medicine.
D-Methionine(CAS NO:348-67-4) has also been given to induce acidosis. In a study to investigate whether the acidosis induced by the metabolism of an oral dose of 11.3 g of D-Methionine would modify ketosis during starvation or ketogenic dieting, the fall in blood pH was similar to that produced by an equivalent dose of ammonium chloride;This could be detrimental to the subjects if continued for extended periods, as metabolic acidosis has been shown to result in an inhibition of muscle protein synthesis in animals .
Moreover, in human volunteers, acidosis resulted in negative nitrogen balance and decreased synthesis of muscle protein and serum albumin which could be detrimental to body protein homeostasis if continued. The acidosis induced by D-Methionine could be the rationale for the prevention of recurrent urinary tract infections by L-Methionine; In another clinical study, D-Methionine (5 or 10 g/d) was given to patients as a treatment for rheumatoid polyarthritis; No serious adverse effects were reported, although nausea, vomiting, constipation, and halitosis were frequent.
D-Methionine is an indispensable amino acid for humans, but there is evidence that if given in excess. It can interfere with the utilization of nitrogen from dispensable amino acids. In studies of nitrogen balance in subjects receiving low-protein diets, nitrogen balance was improved in subjects receiving low protein plus urea or low protein plus glycine, but not with diets containing low protein plus D-Methionine or low protein plus both D-Methionine and urea; Also, the urinary excretion of 5-L-oxoproline, a marker of glycine availability, was significantly lower when the diets contained low protein plus urea or low protein plus urea and D-Methionine.
There was a significant correlation between the excretion of 5-L-oxoproline and excretion of sulfate. The interpretation was that glycine was consumed to detoxify the excess D-Methionine, with the result that the availability of glycine for other metabolic processes became limiting.