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Sources and physiological effects

Dietary sources
The proteinogenic amino acid L-methionine is the only sulfur-containing amino acid that is essential for the human organism. The body is therefore dependent on an exogenous supply. Brazil nuts contain particularly high amounts of L-methionine. Other good sources of the sulfur-containing amino acid include meat, chicken eggs, salmon, soybeans and walnuts.
Physiological effects
Protein synthesis	Starter amino acid in protein synthesis anabolic metabolism
Antioxidant	Precursor of L-cysteine and L-glutathione
Homocysteine metabolism	Homocysteine is converted to methionine via methylation.
Liver	Detoxification of paracetamol and lead Prevention of excessive fat storage Promotion of liver regeneration
Acid-base balance	Decrease of bacterial growth in the bladder by uric acidification. Prevents kidney stone formation.

Recommended intake

Recommended intake
Adults	13 mg/kg bw daily
Toddlers	39 mg/kg bw daily
Increased demand	Use of paracetamol, radiotherapy, cytostatics, competitive sports, stress, protein deficiency, in diseases such as urinary tract infections

Recommended intake according to food labelling regulatitons (=100 % TB-marking on label)
		N/A
Nutrient safety
UL	Long-term daily intake, at which no negative health effects are to be expected	N/A
NOAEL	Maximum intake, with no observed adverse effect	100 mg/kg/d (single dose)*
	No increase in homocysteine levels was found in 4 mg/kg/d in the long term.*	*

Detailed information

Physiological functions of L-methionine

The essential amino acid L-methionine serves in the human organism both as a source of sulfur and as a methyl group donor. The sulfate groups required for the biosynthesis of glycosaminoglycans and crosslinks in collagen structures originate from methionine and cysteine. Methionine is also the precursor of S-adenosylmethionine, which provides the methyl groups for the formation of purines and pyrimidines (1).
Methionine is one of the limiting amino acids in a number of foods from the legumes group. Limiting amino acids determine the biological value of dietary protein for the body's own protein synthesis. Through the targeted supplementation of the limiting methionine, a higher proportion of the amino acids offered can be used for the synthesis of endogenous proteins, which improves the biological value of the dietary protein (2).
S-adenosylmethionine seems to play an important role in the conversion of the genetic code, in repair processes in DNA and RNA and in epigenetic modifications. In addition, S-adenosylmethionine can bind to RNA components and thereby regulate gene expression. This makes this substance a special focus of research (3).

Complementary therapy for urinary tract diseases

Methionine is used as a uric acid substance for the prophylaxis and therapy of urinary tract infections and stone diseases caused by alkalizing bacterial strains (4). The urease of these bacteria splits urea into carbon dioxide and ammonia, which leads to a shift in the pH value of the urine into the alkaline range. Acidification of the urine with methionine slows down the growth of these bacteria. At the same time, the effectiveness of antibiotics with an acidic optima (e.g. ampicillin, carbenicillin, sulfonamides, nalidixic acid, nitrofurantoin) is increased (5).
Supplementation with methionine is also used to improve the solubility of phosphate stones (struvite, carbonatapatite, brushite) and to prevent stone recurrence. As a rule, 500 – 1000 mg L-methionine is recommended 3 times daily (5).

Detoxification and elimination functions

Methionine and the S-adenosylmethionine formed from it contribute significantly as methyl group donors to the detoxification functions in the liver cell. This plays an important role especially in paracetamol poisoning and in the prevention and therapy of fatty liver caused by alcohol. A targeted supply of sulfur-containing amino acids also increases the mobilization of heavy metals from their depots (6). Mercury has a high affinity to methionine, but also the detoxification of arsenic is mainly controlled by methionine metabolites (7).

Sulfur-containing amino acids as building blocks for hair and nails

The sufur-containing amino acids are important sources of sulfur, which makes a significant contribution to the development of collagen structures of nails and hair (6). An undersupply can impair hair production, which can lead to slower hair growth and diffuse hair loss.

Methionine and homocysteine levels

Methionine is directly related to homocysteine metabolism. L-methionine is first converted to S-adenosylmethionine and in further stages to homocysteine. If the vitamins required for homocysteine degradation, folic acid, vitamin B₆ and vitamin B₁₂, are missing, regular supplementation with L-methionine can lead to an increase in homocysteine levels. In clinical trials, 1500 mg/day of methionine led to a significant increase in plasma homocysteine levels of 2 µmol/l even with adequate vitamin status (8). An additional supply of L-methionine of about 1000 mg/day is also considered problematic by other authors (9). A simultaneous supply of vitamins B₆, B₁₂ and folic acid, improves the degradation processes and thus counteracts increased homocysteine values.

Reference values

Nutrigenetics
Characteristic gene sites and their effects on vitamin requirements

Gene

rsNumber

risk SNP

Description

Recommended nutrients

MTR,
MTRR

rs1805087,
rs1801394

G

The transmethylation of this enzyme is reduced. A reduced synthesis of phosphatidylcholine and increased dependence on choline is associated with this SNP (10).

Folic acid, Methionine,
Choline

Deficiency symptoms

Impact on	Symptoms
Skin	Wound healing disorder
Immune system	Increased susceptibility to infections
Muscles	Muscle degradation
Metabolism	Disruption of amino acid balance, negative nitrogen balance

Indications

Effect	Indication	Dosage
Physiological effects at a low intake	To increase the biological value of vegetable protein from pulses in times of increased protein requirement	300 - 500 mg/d
	Complementary therapy for uric acidosis in recurrent infections of the urinary tract; to optimize the action of antibiotics in acid urine (pH 4-6); to prevent stone formation (phosphate stones)	1500 - 3000 mg/d
	For mercury and arsenic elimination	1500 - 3000 mg/d
	Complementary therapy for hair loss, brittle nails and to optimize sulfur supply	300 - 500 mg/d

Administration

General mode of administration
When	L-methionine should be taken between meals.
	Notes: In very high doses the pH value can be shifted (acidosis), leading to increased calcium excretion. For long-term use, due to the risk of hyperhomocysteinemia, an adequate intake of folic acid, vitamin B₆ and vitamin B₁₂ should be ensured.
Side effects
In rare cases nausea or diarrhea occurs.
Contraindications
Acidosis, hyperuricemia, uric acid, oxalate and cysteine stones, hyperhomocysteinuria, hepatic encephalopathy, severe hepatic insufficiency

Interactions

Drug interactions
Antibiotics (ampicillin, sulfonamides, nitrofurantoin)	Methionine leads to acidification of the urine and to increased reabsorption of antibiotics and inhibition of bacterial growth.
Antiparkinson medication (L-Dopa)	Simultaneous administration may worsen the efficacy of L-dopa.
Analgetics (paracetamol)	L-methionine reduces the liver toxicity of paracetamol.
Nutrient interactions
Vitamins	Folic acid, vitamin B₆ and vitamin B₁₂ are essential for methionine homocysteine metabolism.
Antioxidants	In combination with other antioxidants methionine shows synergistic effects.

Description and related substances

Description

Proteinogenic, essential, sulfur-containing amino acid

Related substances

L-methionine (natural form) DL-methionine (racemate in animal feed).

References

1) Hahn, A. et al. 2005. Ernährung. Physiologische Grundlagen, Prävention, Therapie.
2) King, F., Burgess, A. 1992. Nutrition for developing countries.
3) Loenen, W. A. 2006. S-adenosylmethionine. Jack of all trades and master of everything? Biochem Soc Trans. 34(2):330-3.
4) Pagonas, N. et al. 2012. Prophylaxis of Recurrent Urinary Tract Infection After Renal Transplantation by Cranberry Juice and L-Methionine. Transplantation Proceedings. 44(10):3017-3021.
5) Gröber, U. 2002. Orthomolekulare Medizin. Ein Leitfaden für Apotheker und Ärzte.
6) Burgerstein, L. 2002. Handbuch Nährstoffe.
7) Pal, S., Chatterjee, A. K. 2004. Protective effect of methionine supplementation on arsenic-induced alteration of glucose homeostasis. Food Chem Toxicol. 42(5):737-42.
8) Ditscheid, B. et al. 2005. Effect of L-methionin supplementation on plasma homocysteine and other free amino acids: a placebo-controlled, double-blind cross-over study. Eur J Clin Nutr. 59(6):768-75
9) Grimble, R. F. 2006. The effects of sulphur amino acid intake on immune function in humans. J Nutr. 136(6Suppl):1660S-1665S).
10) Ganz, A.B, et al. 2016. Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis. FASEB J. 30(10):3321-3333.

References Interactions
Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.
Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.
Gröber, U. Arzneimittel und Mikronährstoffe: Medikationsorientierte Supplementierung, 3. aktualisierte und erweiterte Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2014.