InteractionsGuide Index Page

 
Case Analysis Toolclose
Enter Each Substance:


Analysis Search Terms:

Methionine

Nutrient Name: Methionine.
Synonyms:DL-Methionine,L-methionine.
Related Substance: S-adenosylmethionine (SAM, SAMe; AdoMet).

Summary Table
nutrient description

Chemistry and Forms

DL-Methionine,L-methionine.

Physiology and Function

Methionine is an essential sulfur-containing amino acid that facilitates and helps initiate the translation of messenger RNA (mRNA) by being the first amino acid incorporated into the N-terminal position of all proteins. The terminal methyl group of the methionine side chain often participates in biochemical methyl transfer reactions, making methionine a member of the “methyl donor” class of biochemicals.

S-adenosylmethionine (SAMe) is intimately involved in the synthesis of brain chemicals and also in detoxification reactions. Methionine is converted into SAMe, which is considered to be the activated form of methionine. This occurs in the first step of the metabolism of methionine, which requires energy in the form of adenosine triphosphate (ATP). In this activation of methionine, an adenosyl moiety is transferred from the ATP molecule. SAMe is one of the most potent methyl donors and is involved in many methylation reactions. Its methyl group, which is attached in a sulfonium linkage with high-energy characteristics, may be donated to any of a large number of methyl-group acceptors in the presence of the appropriate enzyme. DNA methylation influences the expression of many genes and depends on the availability of methyl groups from SAMe. SAMe is intimately involved in the synthesis of neurotransmitters and also in detoxification reactions.

Along with inositol, choline (tetramethylglycine), and betaine (trimethylglycine), methionine is considered a member of the group of compounds called lipotropics that are closely involved in lipid metabolism. Transmethylation metabolic pathways closely interconnect choline, methionine, methyltetrahydrofolate (methyl-THF), and vitamins B6and B12. Methionine can be formed from homocysteine using methyl groups from methyl-THF, or using methyl groups from betaine that are derived from choline. Through interrelated pathways, methyl-THF can be formed from one-carbon units derived from serine or from the methyl groups of choline via dimethylglycine, and choline can be synthesized de novo using methyl groups derived from methionine (via SAMe).

Methionine regulates several sulfur-containing compounds in the body that play an important role in liver detoxification processes and the synthesis of structural proteins and enzymes. It acts as a sulfur donor and, as such, is the source of sulfur for biosynthesis of cysteine. Methionine is also the precursor for the synthesis of cystine and taurine and is one of three amino acids required for the synthesis of creatine. Methionine may serve as a precursor for the synthesis of glutathione, which is the substrate for glutathione peroxidase, a crucial antioxidant enzyme. Methionine assists in the metabolism of homocysteine and helps reduce histamine levels.

nutrient in clinical practice

Known or Potential Therapeutic Uses

Methionine is an essential amino acid which is primarily administered to enhance liver functions such as detoxification and lipid metabolism and to support the function of the central nervous system (CNS) and neurotransmitters. In nutritional therapeutics, methionine can be used to increase levels of SAMe, reduced glutathione (GSH), taurine, and N-acetylcysteine (NAC) and to promote detoxification of xenobiotics via the sulfation pathway.

Historical/Ethnomedicine Precedent

Not used historically as an isolated nutrient.

Possible Uses

Acrodermatitis enteropathica, AIDS-related dementia, AIDS-related nervous system degeneration, fat maldigestion, human immunodeficiency virus (HIV) support, liver detoxification, migraine headaches, pain control, pancreatitis, Parkinson’s disease, radiation effects, schizophrenia, urinary tract infections, weight loss, Wilson’s disease.

Deficiency Symptoms

Typical symptoms associated with methionine deficiency include hair loss, hepatic dysfunction, poor skin tone, and toxic elevation of metabolic waste products.

Methionine deficiency is usually related to overall protein malnutrition. Individuals with acquired immunodeficiency syndrome (AIDS) demonstrate low levels of methionine. Experimentally, a methionine deficiency causes premature atherosclerosis in monkeys, especially if they are also deficient in vitamin B6. Methionine deficiency can also cause a folate deficiency since a deficiency causes 5-methyl-THF to accumulate in the liver. Lower methionine intake during pregnancy has been associated with neural tube defects in newborns.

Dietary Sources

Dairy products, fish, and meat (beef, chicken, pork, liver) are considered the richest dietary sources of methionine. Sunflower seeds, pumpkin seeds, sesame seeds, and lentils are also good sources of methionine. Egg yolks are particularly high in sulfur. Methionine and cysteine make up 91% of the sulfur in the yolk. Endogenous gut flora may be able to synthesize significant amounts. Homocysteine in the diet can eliminate the requirement for methionine.

Soybeans are a poor source, and soy-based infant formulas are generally low in methionine.

Dosage Forms Available

Capsule, powder, tablet; oral and intravenous (IV) administration.

Source Materials for Nutrient Preparations

MostL-methionine in supplements is produced by bacterial fermentation processes in a growth medium, from which the amino acid is then purified. Methionine used in supplements is frequently of theDLform, which implies chemical synthesis, thus resulting in a racemic mixture.

Dosage Range

Adult

  • Dietary:   No reference (recommended) daily intake (RDI) has been established. Average intake in the United States is 2.7 to 5 g per day.
  • Supplemental/Maintenance:   Dietary sources of methionine are usually adequate so supplemental methionine is usually not considered necessary. Optimal levels of intake have not been established but probably are 800 to 1000 mg daily, depending on weight, diet, and related factors.
  • Pharmacological/Therapeutic:   500 to 3000 mg per day.
  • Toxic:   No toxic dose level has been reported.

Pediatric (<18 Years)

  • Dietary:   No minimal dietary requirement established.
  • Supplemental/Maintenance:   Not currently recommended for children.
  • Pharmacological/Therapeutic:   Specific treatment recommendations have not established.
  • Toxic:   No toxic dosage level established specifically for infants and children.

Laboratory Values

Serum or Plasma Methionine

Range of normal levels for plasma methionine:

  • Children: 13 to 30 µmol/L
  • Adults: 16 to 30 µmol/L

safety profile

Overview

Methionine is usually tolerated well by most adults and generally considered to be free of adverse effects for most individuals at common dosage levels (e.g., 1-3 g/day). Toxicity is rare but possible with excessive dosage. Diets high in methionine may be associated with an increased occurrence of atherosclerosis, especially with concurrent deficiencies of vitamin B6, vitamin B12, and folic acid, resulting from elevations of blood homocysteine levels.

Nutrient Adverse Effects

General Adverse Effects

Nausea and gastrointestinal (GI) irritation are the primary signs of methionine toxicity, although occurrence is rare. Some sensitive individuals may experience gas, bloating, and digestive discomfort at levels as low as 500 mg per day. Other symptoms reportedly associated with methionine toxicity may include anorexia, ataxia, hyperactivity, reduced growth, hemosiderosis, and suppressed hematocrit. Extremely high doses may increase urinary calcium excretion and could potentially induce hallucinations. However, administration of up to 2 g daily for extended periods has not been associated with any serious adverse effects.

Rats fed methionine as 50% of dietary protein (equivalent human dose of 25 g/day) exhibited hyperactivity, anorexia, reduced growth, and iron accumulation in the spleen.

Pregnancy and Nursing

Evidence is lacking within the scientific literature to suggest or confirm any adverse effects related to fetal development during pregnancy or to infants who are breast-fed associated with methionine administration. Caution still advised.

Infants and Children

No adverse effects have been reported. However, sufficient research-based evidence is lacking to guarantee the safety of methionine in infants and children.

Contraindications

Avoid S-adenosylmethionine (SAMe) in Parkinson’s disease; administration may aggravate symptoms caused by serotonergic effect.

Precautions and Warnings

Large intakes of methionine require higher intakes of methyl donor–related nutrients, such as B12, folic acid, pyridoxine, choline (tetramethylglycine), betaine (trimethylglycine), and dimethylglycine. Large loads of dietary methionine without concomitant intake of these interdependent nutrients at adequate levels can increase the conversion of methionine to homocysteine (Hcy) and will result in higher levels of Hcy, a vasculotoxic product of intermediary metabolism. Need for methyl donor nutrients in relation to methionine intake varies according to pharmacogenomic determinants, such as methyl-THF reductase enzyme activity. In cases of strong family history of coronary heart disease, it would be judicious to check Hcy levels before and during methionine treatment, because of the potential homocysteinergic and atherogenic effects of methionine.

Animal research conducted by Toborek and Hennig 1 suggests that high dietary intake of methionine, in the presence of B-vitamin deficiencies, may increase the risk for atherosclerosis by increasing blood levels of cholesterol and Hcy. Troen et al. 2 observed that apolipoprotein E–deficient mice fed methionine-rich diets developed significant atheromatous pathology in the aortic arch, even with normal plasma Hcy levels. These findings suggest that moderate increases in methionine intake are atherogenic in susceptible mice.

Administration may be inappropriate in individuals with osteoporosis because high dosage levels increase urinary excretion of calcium.

interactions review

Strategic Considerations

The issue of methionine function and exogenous administration in individuals with Parkinson’s disease and related degenerative neurotransmitter conditions remains unclear, inconclusive, and contentious. Preliminary research by Smythies and Halsey suggests that methionine (5 g/day) may help ameliorate some symptoms of Parkinson’s disease. However, some authors have suggested that exogenous methionine, as with other amino acids, may interfere with the absorption or action of the levodopa, particularly in the treatment of individuals with Parkinson’s disease. Several studies have reported elevated plasma levels of total Hcy, along with decreased methionine and SAMe, in patients treated long term with levodopa and dopa decarboxylase inhibitors (DDIs) as a result of alterations in levels of substrates of the O-methylation cycle. 3

Several studies have investigated the use of methionine coadministration as a means of reducing toxicity caused by acetaminophen and suggested the probable benefits of such an integrative approach to prescribing.

Viewing methionine administration or supplementation within the larger context of wellness and therapeutics, it is important to note that increasing intake of methionine without providing for adequate intake of folic acid, vitamin B6, and vitamin B12can augment the conversion of methionine to Hcy and thereby increase cardiovascular risk.

nutrient-drug interactions
Acetaminophen
Levodopa
theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Vidarabine

  • Evidence:

    Vidarabine (Ara-A, arabinoside; Vira-A).

  • Similar properties but evidence lacking for extrapolation:

    Related nucleoside antivirals.

The most common use of vidarabine is as an ophthalmic preparation for the treatment of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in acute keratoconjunctivitis and recurrent superficial keratitis. The therapeutic action of vidarabine is achieved by interfering with viral DNA synthesis, specifically inhibition of S-adenosylhomocysteine hydrolase (SAH), methionine synthesis, and SAMe-dependent DNA methylation. 17-19 Vidarabine cannot be given orally because it is metabolized in the gut, so it is usually administered intravenously or topically.

The action of vidarabine indicates a potential risk for interfering with methionine function in humans and potentially inducing a depletion of methionine with extended use. Any such depleting effect on methionine status is likely to be gradual and cumulative, but evidence from human trials is lacking. Concomitant administration of methionine (or SAMe) could theoretically interfere with the therapeutic activity of vidarabine or related antiviral medications.

It has long been established that vidarabine is known to interfere with methionine synthesis, although recent and substantial research is lacking. 17,18 Human studies are lacking to determine whether vidarabine might induce clinically significant methionine depletion or whether methionine administration might interfere with the medication’s antiviral activity. Further research is warranted.

Physicians prescribing vidarabine for an extended period are advised to discuss options for countering the potential adverse effects of this medication. Some nutritionally oriented physicians have found value in monitoring serum methionine in their patients taking vidarabine. Close monitoring is warranted in cases where methionine administration is indicated so as to prevent potential reduction of drug efficacy.

nutrient-nutrient interactions
Antioxidants
Folate, Vitamin B 6 , and Vitamin B 12
Citations and Reference Literature
  • 1.Toborek M, Hennig B. Is methionine an atherogenic amino acid? J Opt Nutr 1994;3:80-83.
  • 2.Troen AM, Lutgens E, Smith DE et al. The atherogenic effect of excess methionine intake. Proc Natl Acad Sci U S A 2003;100:15089-15094.View Abstract
  • 3.Muller T, Woitalla D, Hauptmann B et al. Decrease of methionine and S-adenosylmethionine and increase of homocysteine in treated patients with Parkinson’s disease. Neurosci Lett 2001;308:54-56.
  • 4.Skoglund LA, Skjelbred P. Comparison of a traditional paracetamol medication and a new paracetamol/paracetamol-methionine ester combination. Eur J Clin Pharmacol 1984;26:573-577.View Abstract
  • 5.Neuvonen PJ, Tokola O, Toivonen ML, Simell O. Methionine in paracetamol tablets, a tool to reduce paracetamol toxicity. Int J Clin Pharmacol Ther Toxicol 1985;23:497-500.View Abstract
  • 6.Neuvonen PJ, Simell O, Tokola O. Why not add methionine to paracetamol tablets? Br Med J Clin Res Ed 1986;293:958.
  • 7.McAuley DF, Hanratty CG, McGurk C et al. Effect of methionine supplementation on endothelial function, plasma homocysteine, and lipid peroxidation. J Toxicol Clin Toxicol 1999;37:435-440.View Abstract
  • 8.Robertson DR, Higginson I, Macklin BS et al. The influence of protein containing meals on the pharmacokinetics of levodopa in healthy volunteers. Br J Clin Pharmacol 1991;31:413-417.View Abstract
  • 9.Meininger V, Flamier A, Phan T et al. [l-Methionine treatment of Parkinson’s disease: preliminary results]. Rev Neurol (Paris) 1982;138:297-303.
  • 10.Smythies JR, Halsey JH. Treatment of Parkinson’s disease with l-methionine. South Med J 1984;77:1577.
  • 11.Pearce LA, Waterbury, L.D. l-Methionine: a possible levodopa antagonist. Neurology (Minneap) 1974;24:640.
  • 12.Surtees R, Hyland K. l-3,4-Dihydroxyphenylalanine (levodopa) lowers central nervous system S-adenosylmethionine concentrations in humans. J Neurol Neurosurg Psychiatry 1990;53:569-572.View Abstract
  • 13.Kuhn W, Roebroek R, Blom H et al. Elevated plasma levels of homocysteine in Parkinson’s disease. Eur Neurol 1998;40:225-227.
  • 14.Muller T, Werne B, Fowler B, Kuhn W. Nigral endothelial dysfunction, homocysteine, and Parkinson’s disease. Lancet 1999;354:126-127.
  • 15.Muller T, Woitalla D, Fowler B, Kuhn W. 3-OMD and homocysteine plasma levels in parkinsonian patients. J Neural Transm 2002;109:175-179.View Abstract
  • 16.Muller T, Renger K, Kuhn W. Levodopa-associated increase of homocysteine levels and sural axonal neurodegeneration. Arch Neurol 2004;61:657-660.View Abstract
  • 17.Vidarabine (Vira-A). Med Lett Drugs Ther 1977;19:42-43.
  • 18.Cantoni GL, Aksamit RR, Kim IK. Methionine biosynthesis and vidarabine therapy. N Engl J Med 1982;307:1079.View Abstract
  • 19.Fabianowska-Majewska K, Duley JA, Simmonds HA. Effects of novel anti-viral adenosine analogues on the activity of S-adenosylhomocysteine hydrolase from human liver. Biochem Pharmacol 1994;48:897-903.View Abstract
  • 20.Uden S, Bilton D, Nathan L et al. Antioxidant therapy for recurrent pancreatitis: placebo-controlled trial. Aliment Pharmacol Ther 1990;4:357-371.View Abstract
  • 21.Carmel R, Melnyk S, James SJ. Cobalamin deficiency with and without neurologic abnormalities: differences in homocysteine and methionine metabolism. Blood 2003;101:3302-3308.
  • .[No authors listed.] Vidarabine (Vira-A). Med Lett Drugs Ther 1977;19(10):42-43.
  • .Apeland T, Mansoor MA, Strandjord RE, et al. Folate, homocysteine and methionine loading in patients on carbamazepine. Acta Neurol Scand 2001;103(5):294-299.
  • .Ben-Shlomo Y, Marmot MG. Survival and cause of death in a cohort of patients with parkinsonism: possible clues to etiology. J Neurol Neurosurg Psychiatry 1995;58:293-299.
  • .Benson R, Crowell B, Hill B, et al. The effects of L-dopa on the activity of methionine adenosyltransferase: relevance to L-dopa therapy and tolerance. Neurochem Res 1993;18(3):325-330.
  • .Bidard JN. et al. Effect de la SAM sur le catabolisme de la dopamine. J Pharmacol (Paris) 1977; 8(I):83-93.
  • .Bidard JN, Fonlupt P, Cronenberger L, et al. [Effect of S-adenosyl-L-methionine on the cerebral and peripheral metabolism of L-dopa.] Arch Int Physiol Biochim 1978;86(4):715-724. [French]
  • .Bidard JN, Sokoloff P, Cronenberger L, et al. [Effect of S-adenosyl-L-homocysteine of dopamine catabolism.] Arch Int Physiol Biochim 1979;87(2):253-264. [French]
  • .Bidard JN, Fonlupt P, Cronenberger L, et al. [Effect of S-adenosyl-L-methionine on the cerebral and peripheral metabolism of L-dopa.] Arch Int Physiol Biochim 1978;86(4):715-724. [French]
  • .Burger R, Nowak H. A new medical approach to the treatment of osteoarthritis: report of an open phase IV study with ademetionin (Gumbaral) SAM. Am J Med 1987;83(Suppl 5A):84-88.
  • .Carretero MV, Latasa MU, Garcia-Trevijano ER, et al. Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine. Biochem Pharmacol 2001;61(9):1119-1128.
  • .Caruso I, Pietrogrande V. Double blind, multicenter study comparing SAM, naproxen, and placebo in the treatment of degenerative joint disease. Am J Med 1987;83(Suppl 5A):66-71. [Italian]
  • .Chambers JC, McGregor A, Jean-Marie J, et al. Acute hyperhomocysteinaemia and endothelial dysfunction. Lancet 1998;351:36-37.
  • .Charlton CG, Crowell B Jr. Parkinson’s disease-like effects of S-adenosyl-L-methionine: effects of L-dopa. Pharmacol Biochem Behav 1992;43:423-431.
  • .Charlton CG, Mack J. Substantia nigra degeneration and tyrosine hydroxylase depletion caused by excess S-adenosylmethionine in the rat brain: support for an excess methylation hypothesis for parkinsonism. Mol Neurobiol 1994;9(1-3):149-161.
  • .Cheng H, Gomes-Trolin C, Aquilonius SM, et al. Levels of L-methionine S-adenosyltransferase activity in erythrocytes and concentrations of S-adenosylmethionine and S-adenosylhomocysteine in whole blood of patients with Parkinson’s disease. Exp Neurol 1997;145(2 Pt 1):580-585.
  • .Chiang EP, Bagley PJ, Selhub J, et al. Abnormal vitamin B(6) status is associated with severity of symptoms in patients with rheumatoid arthritis. Am J Med 2003;114(4):283-287.
  • .Coppen A, Metcalfe M, Carroll JD, et al. Levodopa and L-tryptophan therapy in Parkinsonism. Lancet 1972;1:654-658.
  • .Crowell BG Jr, Benson R, Shockley D, et al. S-adenosyl-L-methionine decreases motor activity in the rat: similarity to Parkinson’s disease-like symptoms. Behav Neural Biol 1993;59:186-193.
  • .Di Rocco A, Rogers JD, Brown R, et al. S-Adenosyl-Methionine improves depression in patients with Parkinson’s disease in an open-label clinical trial. Mov Disord 2000;15(6):1225-1229.
  • .Donaldson WE, Leming TK. Effect of dietary methionine and lysine on the toxicity of ingested lead acetate in the chick. J Nutr 1984;114:2155-2159.
  • .Dorfman D, DiRocco A, Simpson D, et al. Oral methionine may improve neuropsychological function in patients with AIDS myelopathy: results of an open-label trial. AIDS 1997;11(8):1066-1067.
  • .Funfstuck R, Straube E, Schildbach O, et al. [Prevention of reinfection by L-methionine in patients with recurrent urinary tract infection.] Med Klin (Munich) 1997;92(10):574-581. [German]
  • .Garlick PJ. Toxicity of methionine in humans. J Nutr 2006;136(6 Suppl):1722S-1725S. (Review)
  • .Glorioso S, Todesco S, Mazzi A, et al. Double-blind multicentre study of the activity of S-adenosylmethionine in hip and knee osteoarthritis. Int J Clin Pharmacol Res 1985;5(1):39-49.
  • .Gomes Trolin C, Regland B, Oreland L. Decreased methionine adenosyltransferase activity in erythrocytes of patients with dementia disorders. Eur Neuropsychopharmacol 1995;5(2):107-114.
  • .Growdon JH, Melamed E, Logue M, et al. Effects of oral L-tyrosine administration on CSF tyrosine and homovanillic acid levels in patients with Parkinson’s disease. Life Sci 1982;30:827-832.
  • .Heller B, Fischer E, Martin R. Therapeutic action of D-phenylalanine in Parkinson’s disease. Arzneim Forsch 1976;26:577-579.
  • .Holven KB, Aukrust P, Holm T, et al. Folic acid treatment reduces chemokine release from peripheral blood mononuclear cells in hyperhomocysteinemic subjects. Arterioscler Thromb Vasc Biol 2002;22(4):699-703.
  • .Jacques PF, Bostom AG, Selhub J, et al. Effects of polymorphisms of methionine synthase and methionine synthase reductase on total plasma homocysteine in the NHLBI Family Heart Study. Atherosclerosis 2003;166(1):49-55.
  • .Kagan BL, Sultzer DL, Rosenlicht N, et al. Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry 1990;147(5):591-595.
  • .Keating JN, Trimble KC, Mulcahy F, et al. Evidence of brain methyltransferase inhibition and early brain involvement in HIV-positive patients. Lancet 1991;337(8747):935-939.
  • .Kramer BC, Yabut JA, Cheong J, et al. Toxicity of glutathione depletion in mesencephalic cultures: a role for arachidonic acid and its lipoxygenase metabolites. Eur J Neurosci 2004;19(2):280-286.
  • .Lamango NS, Ayuk-Takem LT, Nesby R, et al. Inhibition mechanism of S-adenosylmethionine-induced movement deficits by prenylcysteine analogs. Pharmacol Biochem Behav 2003;76(3-4):433-442.
  • .Leach FN, Braganza JM. Methionine is important in treatment of chronic pancreatitis. Br Med J 1998;316:474. (Letter)
  • .Lehmann J. Tryptophan malabsorption in levodopa-treated parkinsonian patients. Acta Med Scand 1973;194:181-189.
  • .Lehmann J. Levodopa and depression in Parkinsonism. Lancet 1971;1:140.
  • .Lieber CS, Packer L. S-Adenosylmethionine: molecular, biological, and clinical aspects: an introduction. Am J Clin Nutr 2002;76(5):1148S-1150S. (Review)
  • .Ma J, Stampfer MJ, Giovannucci E, et al. Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res 1997;57(6):1098-1102.
  • .Maree KA, van der Westhuyzen J, Metz J. Interrelationship between serum concentrations of methionine, vitamin B12 and folate. Int J Vitam Nutr Res 1990;60(2):136-141.
  • .Marz R. Medical nutrition from Marz. 2nd ed. Portland, OR: Omni Press; 1997.
  • .Matthias D, Becker CH, Riezler R, et al. Homocysteine induced arteriosclerosis-like alterations of the aorta in normotensive and hypertensive rats following application of high doses of methionine. Atherosclerosis 1996;122(2):201-216.
  • .McAuley DF, Hanratty CG, McGurk C, et al. Effect of methionine supplementation on endothelial function, plasma homocysteine, and lipid peroxidation. J Toxicol Clin Toxicol 1999;37(4):435-440.
  • .Meininger V, Flamier A, Phan T, et al. [L-Methionine treatment of Parkinson’s disease: preliminary results.] Rev Neurol (Paris) 1982;138(4):297-303. [French]
  • .Mirza B, Hadberg H, Thomsen P, et al. The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinson’s disease. Neuroscience 2000;95:425-432.
  • .Moundras C, Remesy C, Levrat MA, et al. Methionine deficiency in rats fed soy protein induces hypercholesterolemia and potentiates lipoprotein susceptibility to peroxidation. Metabolism 1995;44(9):1146-1152.
  • .Muller-Fassbender H. Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. Am J Med 1987;83(5A):81-83.
  • .Muller F, Svardal AM, Aukrust P, et al. Elevated plasma concentration of reduced homocysteine in patients with human immunodeficiency virus infection. Am J Clin Nutr 1996;63(2):242-248.
  • .Niculescu MD, Zeisel SH. Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline. J Nutr 2002;132(8 Suppl):2333S-2335S.
  • .Nutt JG, Woodward WR, Hammerstad JP, et al. The "on-off" phenomenon in Parkinson’s disease: relation to levodopa absorption and transport. N Engl J Med 1984;310(8):483-488.
  • .O’Suilleabhain P, Diaz-Arrastia R. Levodopa elevates homocysteine: is this a problem? Arch Neurol 2004;61(5):633-634. (Editorial, Comment)
  • .Revillard JP, Vincent CM, Favier AE, et al. Lipid peroxidation in human immunodeficiency virus infection. J Acquir Immune Defic Syndr 1992;5(6):637-638.
  • .Rosenbaum JF, Fava M, Falk WE, et al. An open-label pilot study of oral S-adenosyl-L-methionine in major depression: interim results. Psychopharmacol Bull 1988;24(1):189-194.
  • .Rudiger H. [Regulatory aspects in methionine biosynthesis.] Hoppe Seylers Z Physiol Chem 1972;353(5):750. [German]
  • .Salmaggi P, Bressa GM, Nicchia G, et al. Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women. Psychother Psychosom 1993;59(1):34-40.
  • .Shapiro SK, Ehninger DJ. Enzyme regulation in the pathway of methionine biosynthesis: molecular conversion of adenosylhomocysteine to adenosylmethionine: ANL-7409. ANL Rep 1967:61-63.
  • .Shaw GM, Velie EM, Schaffer DM. Is dietary intake of methionine associated with a reduction in risk for neural tube defect-associated pregnancies? Teratology 1997;56:295-299.
  • .Singer P, Katz DP, Dillon L, et al. Nutritional aspects of the acquired immunodeficiency syndrome. Am J Gastroenterol 1992;87(3):265-273. (Review)
  • .Smythies JR, Halsey JH. Treatment of Parkinson’s disease with L-methionine. South Med J 1984;77(12):1577.
  • .Song YS, Rosenfeld ME. Methionine-induced hyperhomocysteinemia promotes superoxide anion generation and NFkappaB activation in peritoneal macrophages of C57BL/6 mice. J Med Food 2004;7(2):229-234.
  • .Tan SV, Guiloff RJ. Hypothesis on the pathogenesis of vacuolar myelopathy, dementia, and peripheral neuropathy in AIDS. J Neurol Neurosurg Psychiatry 1998 65:23-28.
  • .Toborek M, Barger SW, Mattson MP, et al. Role of glutathione redox cycle in TNF-alpha-mediated endothelial cell dysfunction. Atherosclerosis 1995;117(2):179-188.
  • .Toborek M, Kopieczna-Grzebieniak E, Drozdz M, et al. Increased lipid peroxidation and antioxidant activity in methionine-induced hepatitis in rabbits. Nutrition 1996;12(7-8):534-537.
  • .Troen AM, Lutgens E, Smith DE, et al. The atherogenic effect of excess methionine intake. Proc Natl Acad Sci U S A 2003;100(25):15089-15094.
  • .Trolin CG, Lofberg C, Trolin G, et al. Brain ATP: L-methionine S-adenosyltransferase (MAT), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH): regional distribution and age-related changes. Eur Neuropsychopharmacol 1994;4(4):469-477.
  • .USDA: Composition of foods: USDA handbook #8. Washington, DC: ARS, USDA; 1976-1986.
  • .Wang ST, Chen HW, Sheen LY, et al. Methionine and cysteine affect glutathione level, glutathione-related enzyme activities and the expression of glutathione S-transferase isozymes in rat hepatocytes. J Nutr 1997;127(11):2135-2141.
  • .Yamaguchi T, Nagatsu T. Effects of tyrosine administration on serum biopterin in normal controls and patients with Parkinson’s disease. Science 1983;219:75-77.
  • .Zhao WQ, Latinwo L, Liu XX, et al. L-dopa upregulates the expression and activities of methionine adenosyl transferase and catechol-O-methyltransferase. Exp Neurol 2001;171(1):127-138.