Introduction

Methionine is an essential amino critical to many cell functions, including the synthesis of proteins. Supplementation of methionine in vivo is typically through L-methionine, DL-methionine, or a methionine hydroxy analog (MHA). L-methionine and D-methionine are two different forms of methionine that differ in spatial configuration. Despite this, usually, when we refer to 'methionine' without an additional term, we mean L-methionine. L-methionine is the biologically active form of methionine. It also occurs naturally in animal and plant proteins. This form of amino acid is used by the body for protein formation and many other metabolic functions. D-methionine, on the other hand, is a form of amino acid that has limited activity and is less present in nature. Therefore, it is not usually used for protein synthesis in living organismsand.

The biological activity

Methionine is an essential sulfur-containing amino acid that plays a vital role in the production of important molecules such as antioxidants (e.g., glutathione, cystathionine), other non-essential amino acids (e.g., carnitine, cysteine, taurine, and creatine), methyl donors (e.g., S-adenosyl methionine), phospholipids (e.g., phosphatidylcholine), and vasodilatory intermediate (e.g., hydrogen sulfide).

Sources

Major dietary methionine sources are eggs, sesame seeds, brazilian nuts, fish, meat, and cereal grains. Normal plasma concentration of methionine ranges from 13 to 45 μM, and its average daily requirement is 10.4 mg/kg body weight/day. Methionine is converted to S-adenosyl methionine (SAM), a universal methyl donor required for methylation via methionine adenosyltransferase 2A. Similarly, other micronutrients such as folate, choline, betaine, vitamin B12, and other B vitamins act as methyl donors. Altered DNA methylation status may lead to metabolic diseases, cancer, and ageing. Therefore, the availability of dietary precursors such as methionine is critical for maintaining methylation status. This suggests that dietary methionine level plays a crucial role in maintaining homeostasis, and either supplementation or restriction of methionine can significantly affect health.

Benefits

Various in vitro and animal studies suggest that both L-methionine supplementation and its restriction have protective effects in metabolic diseases and may extend life span. However, clinical studies present conflicting or inconclusive results. Interestingly, the major benefits of methionine restriction (MR) and supplementation are imparted via common mechanisms such as regulation of oxidative stress, improved insulin sensitivity and glucose tolerance, modulation of inflammatory signalling, and one-carbon metabolism. Restriction of dietary methionine intake was shown to enhance metabolic flexibility, improve lipid profiles, and reduce fat deposition.

However, long-term dietary restriction of L-methionine leads to adverse events such as bone-related disorders, stunted growth, and hyperhomocysteinemia. Conversely, dietary supplementation of methionine improves hepatic steatosis, insulin resistance, inflammation, fibrosis, and bone health. However, a high level of methionine intake shows adverse effects such as hyperhomocysteinemia, reduced body weight, and increased cholesterol levels. Therefore, dietary methionine in a safe dose could have medicinal value.