Overmethylated vs. undermethylated seems to be one of those things that everyone defines a different way, so let’s talk about it and see if we can bring some clarity. The terms overmethylation and undermethylation make the most sense to me as the Walsh Research Institute uses them. These are general physical tendencies based on the sum of your genetics, nutritional status and body burden. There isn’t one gene or genetic defect alone that can account for them – so just because you have an MTHFR C677T mutation doesn’t actually mean you’re over or under methylated (although it would be one factor that might push the balance to undermethylation). Dr. Walsh describes one’s methylation status as being like a tug of war between opposing factors. Many of those are genetic and some are nutritional or environmental.
Overmethylation MTHFR
This is less common than undermethylation. According to Dr. Walsh’s research, 70% of the population are normal methylators, 22% are undermethylators and 8% are overmethylators. Overmethylation in this context means that the methylation cycle as a whole is sped up, or downstream reactions that use SAMe (the ultimate product of the methylation cycle) are compromised in such a way that there is too much SAMe floating around wanting to methylate something.
- Clinically overmethylators are more likely to have agitated or anxious conditions. Frequently panic or anxiety attacks (64% of panic/anxiety clients at the Walsh Research Institute), paranoid schizophrenia (52% of paranoid schizophrenic clients at WRI were overmethylators), ADHD (28%), behaviour disorders (23%), depression (18%). Depression can occur in under, normal or over methylators but 18% of depressed clients of Dr. Walsh are overmethylators.
- Mutations most likely to contribute to overmethylation are AGAT, GAMT, CBS and MT. MTHFR mutation usually pushes towards undermethylation (but I myself am compound heterozygous MTHFR and an overmethylator) Remember that the presence of one or more of these mutations isn’t enough to say if you’re an over or under methylator. The combination of all of your genetic factors as well as your nutritional state must be taken into account. The best way to determine is through symptoms and traits.
- Other contributing factors are impaired creatine synthesis. This is because Approximately 70% of the SAMe from the methylation cycle is used by creatine synthesis, so if this is impaired the SAMe is used more slowly. This can be due to genetic factors (AGAT or GAMP) or due to deficiencies of arginine or glycine. Also impaired cystathione synthesis, or other polymorphisms in methyltransferase SNPs that account for the rest of the SAMe use.
- Overmethylation leads to excessively high activity of dopamine, norepinephrine and epinephrine in the brain.
If this reminds you of you, you could be overmethylated. A photograph of Robin Williams taken by Michael Dressler in 1979, later used as a cover photo for Time magazine to highlight Williams.
- Symptoms and traits of overmethylation include:
- High anxiety
- Sleep disorder
- High energy, restless, must move and fidget
- Verbose or talkative
- Often high artistic or musical ability
- Antihistamine intolerance (makes anxiety or restlessness worse)
- Overly empathetic with others
- Non-competitive in sports
- Tendency towards food and chemical sensitivities
- Less likely to have seasonal allergies
- Histamine Intolerance (or HIT – this is essentially a food sensitivity to high-histamine foods)
- Low libido
- Dry eyes and mouth
- Adverse reaction to SSRI drugs, SAMe or methionine (typically all make anxiety or depression much much worse.
- An easy way to picture this type is by using Robin Williams as an example.
Is Overmethylated the Same as Over-supplemented?
No, although it seems that in a lot of popular literature on the subject people use the term interchangeably. So often you’ll see someone say that you might be “overmethylated” if you are taking too much 5-MTHF or SAMe. I feel that these are different things entirely. If you have a tendency to be overmethylated then certainly you would probably feel worse taking something like SAMe, but even without that you are still an overmethylator (in my opinion). Likewise taking too much 5-MTHF, doesn’t make you suddenly “overmethylated” it just means you’re taking too much.
Okay! I’m Overmethylated. Now What?
Interestingly the best way to balance the consequence of overmethylation, is still 5-MTHF. This seems strange, because it is also the answer if you’re’ undermethylated, but the effects are actually coming from a different mechanism. Folate actually reduces activity at serotonin, dopamine and norepinephrine synapses. 5-MTHF is the active form of folic acid, and you can also get it from foods, especially if you have some trouble taking the supplement. Trouble taking the supplement is surprisingly common, although I think less common clinically in overmethylators (in my experience) than in undermethylators. Niacin or niacinamide can also be helpful for overmethylators as they quench some of the excessive methylation. Again, start slowly.
I Want to Start Taking 5-MTHF. How Do I Make This Easy?
Any time you start taking 5-MTHF, or increase your dose, there will be an adjustment period. Here’s a whole post on it. Just remember, start with a low dose and increase really slowly. This is changing the way your neurotransmitters work and doing some heavy detox work, so it’s vital not to overdo it because that is crazy-making. Start low and go slow.