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Overmethylation – an MTHFR Basic State

Overmethylation, as we have discussed, is the least common state according to the research of Dr. Carl Pfeiffer in his book Nutrition and Mental Illness, An Orthomolecular Approach To Balancing Body Chemistry. Ovmethylation isn’t caused by just one thing – it’s a tendency based on your genes, lifestyle, stressors, diet, and environment. Interestingly – you can be an overmethylator without having an MTHFR mutation at all. Overmethylation also flows on a spectrum, from very mild symptoms to far more severe ones.

If you’re not sure if you’re an undermethylator, methylation neutral, or an overmethylator then visit this post for a comparative chart. As with everything else, even the most severely overmethylated person will have some traits and not others – this is all very individual. The biggest constants are artistic or creative tendencies, empathy and/or social activism, and anxiety.

Balanced overmethylators can change the world with their compassion, empathy and creativity

Overmethylators Are Blessed With Many Positive Traits.

  • Creative
  • Highly artistic or musical
  • Highly empathic and sensitive
  • March to the beat of their own drum
  • Passionate and self-sacrificing
  • High pain threshold

Some of These Traits Have a Darker Side:

  • Obsessive or manic focus on what is important to them (social cause, activism, artistic project)
  • Ruminating – hard to shut brain off
  • Sleep disorders
  • Anxiety
  • A tendency toward self-enhancement (extreme plastic surgery, implants of all types), tattoos, piercings

Overmethylation Can Lead to Physical and Medical Issues

  • Food and chemical sensitivities – this picture is dominated by low histamine which then translates to alternate immune pathway sensitivities.
  • Pain – head, neck, and general body pain.
  • Low Histamine
  • Anxiety or panic
  • Sleep disorders – especially with physical or mental restlessness.
  • Depression – depression – especially with an anxiety component
  • Hyperactivity, ADHD – in combo with restlessness and anxiety

At The Extreme End of Pathology Overmethylators Can Be Prone To:

  • Schizophrenia
  • Panic attacks
  • Self-mutilation or self-harm
  • Major Depression
  • Bipolar Disorder
  • Psychosis including post-partum psychosis

Nutritional Tendencies In Overmethylation

  • Great Reactions to B Vitamins – most overmethylators are low in B vitamins generally, but especially folate and B12 and typically do well with higher than average dosages.
  • Often high copper levels, which can be balanced by increasing zinc
  • Often low histamine
  • Often low B3 and B6
  • Often intolerant to estrogen therapies including birth control and HRT
  • Serotonin, dopamine and norepinephrine may be elevated

Medication and Supplement Reactions in Overmethylation

Overmethylation changes the way your body reacts to certain prescriptions and medications
There is a possibility that overmethylation can change how your body reacts to certain medications and prescriptions

This represents what is typical for the group, but drug and nutrient reactions can be very personal, so this is a general guideline and not a certainty. This information is both from Dr. Pfeiffer’s book (see above), this article, and my own experience with clients.

Typically Good ReactionTypically Bad Reaction
BenzodiazepinesSSRI Antidepressants
Lithium (Rx) or Lithium OrotateAntihistamines
High-folate foodsEstrogen – birth control pills, hormone replacement therapy
Folate, Folinic Acid, 5-LMTHFSAMe
B3, B6Copper
ZincTryptophan, phenylalanine
Antioxidants – C, E, A, NAC, etc…St John’s Wort
MagnesiumDMG, TMG (methyl donors)
Omega-3 fatty acids

You can read more about overmethylation here.

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MTHFR is a common genetic mutation that can contribute to anxiety, depression, fatigue, chronic pain, infertility, and more serious conditions like breast implant illness, heart attack, stroke, chronic fatigue syndrome, and some types of cancer. If you know or suspect you have an MTHFR variant, schedule a free 15-minute meet-and-greet appointment with MTHFR expert Dr. Amy today.

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Amy Neuzil
Amy Neuzil

Dr. Amy Neuzil, N.D. is a leading expert in MTHFR and epigenetics, and she is passionate about helping people achieve optimal health and wellness for their genetic picture. She has helped thousands of people overcome health challenges using a simple, step-by-step approach that starts with where they are today. Dr. Neuzil's unique approach to wellness has helped countless people improve their energy levels, lose weight, and feel better mentally and emotionally. If you're looking for a way to feel your best, Dr. Amy Neuzil can help. Contact her today to learn more about how she can help you achieve optimal health and wellness.

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  1. OMG, this is me, but not on the “Extreme” end. I’m more between the dark side and physical end. Of all the things you said overmethylators react to, I definitely react to them all after a couple of days, then have to stop them and need time to recover. My ND had me try the TMG when I first started seeing her, and she was surprised that I couldn’t tolerate it… same thing with the Inositol that she recommended. And now I think I’m reacting to a higher dosage on my 2x/weekly estradiol patch. When my folate level was 3, my primary’s nurse didn’t believe me when I told her that the methylfolate they wanted me to take made me feel weird and exhausted. What’s an overmethylator to do? I have a trayful of supplements that I have to take individually (learned by trial and error), as the multi vitamins are filled with methyls that make me feel horrible. My dailies are Ginger, Folinic acid, Zinc, Adenosyl Hydroxy B12, B1, B2, Co-enzymated B6, and Niacinamide.

    • Hi Donna,
      I have done a lot of research lately and find it interesting to see that what you take daily correspondents with my research. Especially the b12 is interesting, my son can’t handle methyl b 12. I am interested in the dosage that you take your vitamins. Are you tested. If so, how. Do you see a health practitioner? Do you have regular blood 🩸 test?

  2. This sounds a lot like me – and the extreme version was my daughter. What about ferritin? I have excessively high ferritin levels.

    • Hi Brenda,
      It’s me, too! I haven’t found a link between the over methylation picture and ferritin levels, but of course we are just touching the tip of the iceberg at this point. There is so much more to learn and know about these pictures. Thanks for being here!

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