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

Abstract

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. Design: A randomized placebo-controlled double-blind intervention study with cross-over design. Setting: Department of Nutritional Physiology, Institute of Nutrition in cooperation with the Department of Internal Medicine III, Friedrich Schiller University of Jena, Germany. Subjects: Eight female patients with chronic urinary tract infection and 12 healthy women (controls). Interventions: 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 B 12 , B 6 and the state of folate. Results: Homocysteine plasma concentrations increased from 9.472.7 mmol/l (patients) and 8.971.8 mmol/l (controls) in the placebo period to 11.274.1 mmol/l (P ¼ 0.031) and 11.072.3 mmol/l (P ¼ 0.000), respectively, during L-methionine supplementation. There were significant increases in serum methionine (53.6722.0 mmol/l; P ¼ 0.003; n ¼ 20) and cystathionine (0.6270.30 mmol/l; P ¼ 0.000; n ¼ 20) concentrations compared with the placebo period (33.0712.0 and 0.3070.10 mmol/l; n ¼ 20). Simultaneously, renal excretion of methionine and homocysteine was significantly higher during L-methionine intake. Conclusions: 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 mmol/l in patients and in control subjects. An optimal vitamin supplementation, especially with folate, might prevent such an increase.

Iron-dependent formation of homocysteine from methionine and other thioethers

“…We used only 25 mg of methionine/kg body weight, which is one-fourth the oral doses that are generally used for methionine (100 mg/kg of body weight) loading test (Ditschield et al, 2005). This dose was equivalent to the methionine content of 200-300 g of meat, and this amount of daily intake is not uncommon (Pennington, 1998).…”

Transmethylation and the redox homeostasis

“…A glutationrendszer (GSH-rendszer) működéséhez szükséges GSH-ban egy ciszteinmolekula található. A cisztein kénatomja a SAM keletkezéséhez szükséges metionintól származik [1,15,21]. A metionin szinté-ziséhez folsav szükséges, amelyet a dihidrofolát-reduktáz NADPH segítségével tetrahidrofoláttá (THF) redukál.…”

“…A metionin szinté-ziséhez folsav szükséges, amelyet a dihidrofolát-reduktáz NADPH segítségével tetrahidrofoláttá (THF) redukál. Kolin, betain és egyéb metildonor vegyületek jelenlé tében a THF képes metil-THF-fé alakulni és transz metilezési folyamatokat katalizálni [21].…”

“…Így a GSH ismét be tud kapcsolódni a ciklusba, és a Se-dependens GSH-peroxidáz segítségével a H 2 O 2 -t víz-zé redukálja. A GSH ciszteinjének kénatomja viszont a transzmetilezés során képződő homociszteintől szár-mazik [15,21].…”

Is iron over-rated? Sulphates may be the more important compound in development of colitis in rodent models, and perhaps humans

“…A high methionine diet leads to increased plasma homocysteine8 and increased cellular homocysteine has been associated with an increase in the in vitro adhesion of monocytes to endothelial cells 9. Surface expression of vascular cell adhesion molecule 1 (VCAM-1) is triggered and secretion of monocyte chemoattractant protein 1 (MCP-1) is stimulated.…”