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MTHFR and Overmethylation

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    What is overmethylation and undermethylation?

    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. 

    Symptoms of Methylation Imbalances

    • Anxiety
    • Adrenal fatigue
    • Depression
    • Inability to concentrate
    • Hyperactivity
    • Panic attacks
    • Poor motivation
    • Easily frustrated
    • Sleep disorders, insomnia
    • Paranoia
    • Sensitivities to foods/chemicals
    • High pain threshold
    • High energy levels
    • Low histamine
    • Infertility or pregnancy issues (trouble conceiving, miscarriages)
    • Hormonal imbalances (polycystic ovarian syndrome, PMS, fibroids, endometriosis etc.)
    • Cardiovascular disorders (high homocysteine)
    • Histamine intolerance (allergies such as hay fever) 
    • Headaches
    • Heart palpitations
    • Flu-like symptoms

    Can too much methylfolate affect methylation?

    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 

    What to do if you think you’re over-methylating

    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.

    Tips for methylation support

    As with any new supplement, we recommend starting with a low dose and increasing slowly to find the dosage range that works best for you.  It may help to check out our page about methylfolate dosage to learn more about how much methylfolate to take as well as our Methylation Protocols to better understand how to supplement according to your specific needs.

    MTHFR and Overmethylation

    Key Takeaways


    Overmethylation is thought to occur when the body has more methyl groups than it needs or can use. Too many methyl groups may upset the proper function of the body’s normal biochemical processes, which may lead to symptoms like anxiety, fatigue, poor concentration, panic attacks, sleep disorders, and sensitivities to environmental toxins. Other reported effects may include headaches, heart palpitations, and flu-like symptoms.


    However, it’s important to note there is little scientific evidence that "over-methylation" is a clinical condition, possibly because it has not been well-studied in Western medicine. Overmethylation is not the same as epigenetic hypermethylation, which occurs in specific genes or regions of DNA.
     

    This article will explain overmethylation, its symptoms, how methylation issues develop and how they can be managed through diet and supplementation.

    • Icon Overmethylation may occur when the body isn’t able to use methyl groups as it should, which can mean certain nutrients are unable to be fully utilized.
    • Icon While imbalances in the methylation process are common, there is little evidence that overmethylation is a real condition.
    • Icon It’s important to examine your symptoms and consider all aspects of your diet, lifestyle, genetics, and other influences.

    Product Recommendations

    L Methylfolate Supplement 2.5 mg

    Rating: 5.0 out of 5 (15)

    $29.00

    • Supports Healthy DNA Synthesis10
    • Promotes Balanced Homocysteine Levels9
    • 3rd-Party Tested for Purity, Potency & Safety
    • 90 Vegan, Non-GMO, Chewable Mint Tablets

    References

    1. Lundi Ly, Donovan Chan, Mahmoud Aarabi, Mylène Landry, Nathalie A Behan, Amanda J MacFarlane, Jacquetta Trasler; "Intergenerational impact of paternal lifetime exposures to both folic acid deficiency and supplementation on reproductive outcomes and imprinted gene methylation"; Molecular human reproduction; 2017 Jul

      https://pubmed.ncbi.nlm.nih.gov/28535307/

    2. Banner Image Designed by Freepik

      https://www.freepik.com/

    Katie Stone - Naturopath

    About the Author

    Katie is a qualified Naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!