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Effect of L-methionine supplementation on plasma homocysteine and other free amino acids: a placebo-controlled double-blind cross-over study



The essential amino acid L-methionine is a potential compound in the prophylaxis of recurrent or relapsing urinary tract infection due to acidification of urine. As an intermediate of L-methionine metabolism, homocysteine is formed. The objective was to study the metabolism of L-methionine and homocysteine, and to assess whether there are differences between patients with chronic urinary tract infection and healthy control subjects.


A randomized placebo-controlled double-blind intervention study with cross-over design.


Department of Nutritional Physiology, Institute of Nutrition in cooperation with the Department of Internal Medicine III, Friedrich Schiller University of Jena, Germany.


Eight female patients with chronic urinary tract infection and 12 healthy women (controls).


After a methionine-loading test, the volunteers received 500 mg L-methionine or a placebo three times daily for 4 weeks.

Main outcome measures:

Serum and urinary concentrations of methionine, homocysteine, cystathionine, cystine, serine, glycine and serum concentrations of vitamin B12, B6 and the state of folate.


Homocysteine plasma concentrations increased from 9.4±2.7 μmol/l (patients) and 8.9±1.8 μmol/l (controls) in the placebo period to 11.2±4.1 μmol/l (P=0.031) and 11.0±2.3 μmol/l (P=0.000), respectively, during L-methionine supplementation. There were significant increases in serum methionine (53.6±22.0 μmol/l; P=0.003; n=20) and cystathionine (0.62±0.30 μmol/l; P=0.000; n=20) concentrations compared with the placebo period (33.0±12.0 and 0.30±0.10 μmol/l; n=20). Simultaneously, renal excretion of methionine and homocysteine was significantly higher during L-methionine intake.


Despite an adequate vitamin status, the supplementation of 1500 mg of L-methionine daily significantly increases homocysteine plasma concentrations by an average of 2.0 μmol/l in patients and in control subjects. An optimal vitamin supplementation, especially with folate, might prevent such an increase.

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Correspondence to G Jahreis.

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Guarantor: G Jahreis.

Contributors: BD: conception, design, conduct of the study, analysis, statistics, data interpretation, writing the manuscript; RF: conception, design, medical attendance; MB: analysis, data interpretation; RS: analysis, data interpretation, statistics; JG: medical attendance; GJ: conception, design, data interpretation.

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Ditscheid, B., Fünfstück, R., Busch, M. et al. Effect of L-methionine supplementation on plasma homocysteine and other free amino acids: a placebo-controlled double-blind cross-over study. Eur J Clin Nutr 59, 768–775 (2005).

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  • L-methionine
  • homocysteine
  • serum amino acids
  • methionine-loading test

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