MTHFR and Overmethylation

Complications in the methylation process are relatively common, particularly undermethylation.

Undermethylation may occur when a mutation in the MTHFR gene impairs the MTHFR enzyme, preventing proper folate conversion. This can lead to a deficiency of methyl groups in the body, which may contribute to various health issues.

Overmethylation, on the other hand, is thought to be much less common. It is believed to occur when the body is unable to effectively use methyl groups, potentially leaving nutrients unutilized. Methyl donors such as folate, choline, and betaine, along with their cofactors (vitamins B12 and B6), play a vital role in maintaining balanced methylation. While excessive intake of these nutrients could theoretically disrupt normal methylation processes, no studies have definitively linked this disruption to a specific health condition.

There is some evidence suggesting that excess intake of folate and other B vitamins can influence DNA methylation. For example, one study found that male offspring of mice fed a high-folate diet experienced decreased sperm counts, altered methylation in key genes, increased postnatal mortality in offspring, and reduced litter sizes.¹

Although disturbances to the methylation process can occur, such as hypermethylation in specific genes, the concept of “overmethylation” lacks robust scientific evidence. 

If you suspect your health issues are linked to methylation imbalances, it’s important to look at all the other factors involved in the issue, such as your diet, lifestyle, environment, and genetic influences. 

Excessive amounts of certain nutrients could affect their role in methylation pathways and neurotransmitter synthesis, possibly leading to temporary side effects in sensitive individuals.This could mean your body has more methyl donors than it can deal with at once.

Remember, methylfolate and B12 are vitamins, so any side effects are typically going to be much less severe than they would be with a pharmaceutical drug.

But if you’re very sensitive to drugs, vitamins and supplements, it’s advisable to start low and increase slowly.

If you are starting methylfolate or have changed your dosage and are experiencing the following symptoms, you may be over-methylating:

• You feel “amped-up” or jittery
• Your heart is racing/pounding/palpitating
• You feel like you've had too much caffeine
• You are agitated/aggravated/irritable
• You feel overwhelmed
• Your anxiety levels have increased 

If you suspect that your body is over-methylating, the first step is to seek help from a qualified health practitioner. Everyone is different, and the right treatment for you must cater to your unique needs. This will require a comprehensive assessment of your symptoms and health history.

Managing overmethylation may involve changes to your diet and lifestyle, and adjusting your dosages. However, most overmethylation reactions will be temporary, as B vitamins are water-soluble and are not stored in the body. 

Tip: Anecdotal evidence suggests that overmethylation symptoms may be managed by supplementing with N-Acetyl Cysteine (NAC) or glutathione. NAC is an important amino acid and the precursor to glutathione, the body’s major antioxidant. Both nutrients may help the body to metabolize excess methyl nutrients more efficiently, potentially alleviating negative symptoms.