L-Methionine: Food Sources, Supplementation, Side Effects

What Are Amino Acids?

When linked together in chains, amino acids form proteins in the body. So, amino acids are like letters of an alphabet being used to form words. The specific number and sequence of amino acids determines the shape and function of the protein. 

Proteins are utilized in all sorts of roles in the body, including those involved in tissue structure and cellular regulation. 

There are twenty different amino acids used by the human body to function correctly. Nine of these amino acids are called essential amino acids and must be consumed in the diet. 

What Is L-Methionine?

 L-methionine is one of the essential amino acids that contains sulfur.

L-Methionine Food Sources

The best dietary sources of methionine: 

• Meat
• Poultry
• Fish
• Eggs
• Dairy Products 

The best plant-based sources:

• Soy Foods
• Brazil Nuts 
• Sunflower Seeds
• Black Beans
• Cashews

L-Methionine Functions

In addition to being used in protein, L-methionine is also converted to a very important molecule in the body known as S-Adenosylmethionine, or SAMe. SAMe is formed from the combination of L-methionine and adenosine triphosphate (ATP), the main “energy molecule” of the body. SAMe plays an integral role in the creation of various hormones, neurotransmitters, and other critical molecules found in the body. SAMe has emerged as an important dietary supplemental form of L-methionine.^[1]

L-methionine is also converted into another sulfur-containing amino acid, L-cysteine, which can also be converted to L-taurine, as well as become a key component of glutathione, a key cellular antioxidant and detoxifying compound.^[1] 

L-Methionine Supplementation

L-methionine supplementation is much different than supplementing with SAMe, which can be viewed as a more active form of L-methionine. L-methionine is available as a single ingredient but is most often included in liver health formulas designed to promote the flow of bile and fat to and from the liver (lipotropic formulas). Other compounds typically found in these formulas are cysteine, choline, inositol, and betaine. The effectiveness of methionine as a lipotropic agent has not been confirmed. 

Deficiency

Amino acids are important for good health, and the body has a very complex system to regulate their levels, balance, and metabolism. Vitamins B6, folate and B12 are also intricately involved in this system. A deficiency of these nutrients impairs L-methionine metabolism, leading to higher levels of a detrimental metabolite known as homocysteine. Elevated homocysteine levels can lead to an increased risk for over 100 different health issues, including heart disease, osteoporosis, cognitive decline, and Alzheimer’s disease.^[2]

Side Effects and Considerations

Supplementation of up to 2 grams of L-methionine daily for long periods of time has not produced any serious side effects in humans. While animal models have shown that a high-methionine diet is associated with increased brain inflammation, cognitive impairment, and lesions characteristic of Alzheimer’s disease, these effects are likely due to the buildup of homocysteine, a known neurotoxin due to inadequate intake of vitamin B6, B12, and folate.^[3]

In humans, it was shown that the ratio of L-methionine to homocysteine is the critical marker. A high ratio of high L-methionine and low homocysteine was associated with a decreased risk of dementia and reduced loss of brain volume. The methionine-to-homocysteine ratio was significantly higher in individuals who consumed vitamin supplements. 

This research indicates that L-methionine supplementation should always include adequate dietary intake or supplementation of vitamin B6, B12, and folate to ensure proper L-methionine metabolism. In contrast to L-methionine, there is no concern with SAMe as this form does not raise homocysteine levels.^[5]

References:

1. Elango R. Methionine Nutrition and Metabolism: Insights from Animal Studies to Inform Human Nutrition. J Nutr. 2020 Oct 1;150(Suppl 1):2518S-2523S. 
2. Smith AD, Refsum H. Homocysteine - from disease biomarker to disease prevention. J Intern Med. 2021 Oct;290(4):826-854.
3. Alachkar A, Agrawal S, Baboldashtian M, Nuseir K, Salazar J, Agrawal A. L-methionine enhances neuroinflammation and impairs neurogenesis: Implication for Alzheimer's disease. J Neuroimmunol. 2022 May 15;366:577843. 
4. Hooshmand B, Refsum H, Smith AD, et al. Association of Methionine to Homocysteine Status With Brain Magnetic Resonance Imaging Measures and Risk of Dementia. JAMA Psychiatry. 2019 Nov 1;76(11):1198-1205. 
5. Thompson MA, Bauer BA, Loehrer LL, et al. Dietary supplement S-adenosyl-L-methionine (AdoMet) effects on plasma homocysteine levels in healthy human subjects: a double-blind, placebo-controlled, randomized clinical trial. J Altern Complement Med. 2009 May;15(5):523-9.