Some sources suggest that those with the homozygous MTHFR 677TT variant is related to an elevated copper:zinc ratio, flavin sufficiency, and a risk of over-methylation. Copper supplements or high intake of copper-rich foods (liver, oysters, spirulina) may make symptoms worse. However, zinc supplementation reduces excess free copper and moderates copper effects in relationship to neurotoxicity, oxidative stress, and thyroid damage.

Zinc supplementation also benefits antioxidant capacity and impairs copper bioavailability. 

Higher levels of inflammatory cytokines in the body can be treated with natural anti-inflammatory agents such as Omega-3 fish oil, turmeric, ginger, and green tea extract.

Undermethylation can occur when methyl molecules are insufficient. Characteristics of undermethylation include high levels of oxidative stress, low vitamin B6, D, and folate levels, and low levels of unbound copper. There is also a tendency for higher histamine. 

Those who undermethylate also tend to have low levels of neurotransmitters, which may increase their risk of depression, anxiety, and low energy. 

Undermethylating is associated with MTHFR 677CT  gene variants due to insufficient folate and other B vitamin cofactors required for the methylation cycle. 

Symptoms of undermethylation may include:

Lower levels of methylation have also been associated with more ADHD symptoms in childhood due to increased neurotransmitter release during brain methylation before birth.

Proper methylation is critical for numerous biochemical pathways in the body. 

Overmethylation and undermethylation can lead to complications with daily function, increasing the risk of physical and mental health issues. 

Undermethylation is most commonly treated with supplements that assist with methylation, including methylfolate and vitamin B12. Choosing a high-quality methylfolate supplement such as Methyl-life’s® Methylfolate range and eating a diet high in methylation-supporting nutrients is also recommended.

Treating overmethylation may involve managing your body’s histamine levels to avoid the elevated levels of serotonin, dopamine, and norepinephrine. NAC, glutathione and nicotinic acid all have methylfolate metabolizing effects. Because they are considered to be methylation cofactors, these nutrients can help the body better absorb & utilize methylfolate and may reduce overmethylation side effects more quickly, therefore bringing the body back into better balance.

High levels of copper may be reduced by supplementing with zinc, manganese, Vitamin C, niacinamide, Vitamin B12, and methylfolate.