Overview
L-methionine is an essential sulfur-containing amino acid that plays a central role in protein synthesis, methylation reactions, and antioxidant defense. It serves as the precursor to S-adenosylmethionine (SAMe), the primary methyl donor in numerous biochemical pathways, including DNA and histone methylation, which are critical for epigenetic regulation and neuronal development [10][1]. Methionine residues in proteins also act as endogenous antioxidants by scavenging reactive oxygen species through reversible oxidation to methionine sulfoxide, a process regulated by methionine sulfoxide reductases [9]. Adequate methionine intake is vital for liver health, lipid metabolism, and homocysteine regulation, although excessive levels may contribute to hyperhomocysteinemia if cofactors such as vitamins B6, B12, and folic acid are insufficient [10][4]. While direct supplementation of L-methionine is not commonly used in clinical practice, its metabolic derivatives like SAMe are studied for liver support and neurological function.
Dosage Guide
Recommended Daily Allowance
For generally healthy individuals
Therapeutic Doses
For treatment of specific conditions
Upper Intake Limit
Maximum safe daily intake
3000 mg— Tolerable upper intake level not firmly established; doses above 2–3 g/day may increase homocysteine without adequate B-vitamins
Special Forms
Alternative forms for specific needs
Liver disease, depression, osteoarthritis – active metabolite of methionine
Potential antioxidant and hepatoprotective agent, less studied
Clinical Notes
- High-dose methionine may elevate homocysteine, increasing cardiovascular risk, especially in individuals with B-vitamin deficiencies
- Avoid in patients with homocystinuria or severe liver disease unless under medical supervision
- Methionine supplementation is contraindicated in individuals with methylenetetrahydrofolate reductase (MTHFR) mutations without concurrent B-vitamin support
- Oral methionine can be used as an alternative to N-acetylcysteine in early acetaminophen overdose in specific settings
- Monitor homocysteine levels when using long-term, high-dose methionine
Research
S-adenosylmethionine (SAMe) shows efficacy and safety in liver diseases, with high-quality evidence supporting its use.
Methionine acts as an antioxidant via reversible oxidation to methionine sulfoxide, protecting proteins from oxidative damage.
Methionine metabolism influences lipid metabolism and produces bioactive compounds like homocysteine, glutathione, and H2S.
Folic acid is a key regulator of homocysteine, which is derived from methionine metabolism and linked to cardiovascular risk.
Homocysteine-lowering with B vitamins does not consistently reduce cardiovascular events despite lowering homocysteine levels.
DL-methionine and its hydroxy analog are effective dietary sources of methionine in pigs, supporting its bioavailability.
Lowering homocysteine with B vitamins did not significantly reduce cardiovascular events in large trials.
Hyperhomocysteinemia is associated with lower HDL and increased cardiovascular risk, modulated by vitamin status.
Methionine oxidation plays a regulatory role in cellular redox signaling and protection.
Methionine cycle integrity is crucial for nervous system development and maintenance, dependent on folate and B12.
