Low levels of essential amino acids may indicate a poor-quality diet, or maldigestion due to deficient digestive peptidase activity or pancreatic dysfunction. 

A dietary methionine deficiency (low intake or malabsorption/maldigestion) can affect the methylation cycle, given its critical role.

Increasing methionine dietary sources, methionine supplementation, or methylated product supplementation can mitigate the adverse impact. Because vitamins B12 and folate are needed to remethylate homocysteine into methionine, functional need for these cofactors may contribute to low methionine levels. 

Lastly, vitamin B3 deficiency has been associated with low levels of several amino acids.

Methionine elevations are most commonly caused by increased dietary intake. However, increases can also be due to abnormalities within the methylation cycle itself producing a passive methionine elevation. Genetic SNPs for several methylation and transsulfuration enzymes, or the lack of necessary vitamin and mineral cofactors, can alter methionine’s metabolism. For example, a nutritional cofactor deficiency (magnesium/potassium), ATP depletion, or a SNP in the MAT enzyme, can downregulate the conversion to SAM and may lead to elevated methionine. 

Vitamin B6 deficiency, a cofactor for the downstream enzyme responsible for homocysteine transsulfuration, can result in excess homocysteine re-methylation back to methionine, thus increasing methionine. 

Additionally, molybdenum is a cofactor in methionine degradation and catabolism, therefore molybdenum insufficiency can contribute to high levels of methionine. 

Mild elevations in methionine do not cause serious adverse clinical effects. There is literature regarding CNS abnormalities seen with excessive elevations, but this is rare and more commonly seen with inborn errors of metabolism (MATI/III deficiency also known as Mudd’s disease).