Walsh Discusses Overmethylation Biotype


Serious conditions such as panic disorders, Biopolar disorder and schizophrenia are often suffering from overmethylation. Serotonin, dopamine and norepinephrine are elevated in these persons. It is possible to diagnose this condition through a whole blood histamine test or else through a SAM/SAH methylation ratio test. Higher levels of these neurotransmitters can cause anxieties, disorders and in some cases psychosis and maybe lead some to suicide. Fortunately supplementation can reverse the symptoms associated with overmethylation. The goal is to reduce the methylation effect of elevated neurotransmitters and lower oxidative stress.

Dr Mercola interviews Dr Walsh on role of epigenetics, methylation and folates in mental health.

The Importance of Methylation and Folates in Mental Health

In his interview with Dr Mercola, Dr Walsh, who pioneered the role of methylation in mental health and autism.  discusses methylation. According to Walsh, the No. 1 causes of undermethylation are single-nucleotide polymorphisms (SNPs) or mutations in the enzymes for the one-carbon cycle (the methylation cycle).

“The No. 1 factor is the methylenetetrahydrofolate reductase (MTHFR), which is one of the enzymes. That’s the rate-limiting step for that whole cycle, for most people,” Walsh explains. “Genetic testing services such as 23andMe can provide this kind of information.

However, most human beings have enormous numbers of SNPs. They’ve already found 10 million snips (or mutations) in the human genome. Every human being has thousands of these SNPs. A really high percentage of people have even the more serious MTHFR SNPs — the C677T, the A1298C that people are always talking about.

The thing that is often mistaken by nutritional scientists is that if a person has the homozygous, the double copies of the C677T, it doesn’t necessarily mean they’re undermethylated. It certainly doesn’t mean that they will benefit if you give them methylfolate. That’s one of the problems that we’re finding.

The reason is epigenetics. You have to consider the epigenetics and the methylation at the same time. There are three nutrient factors that affect epigenetics more than anything else: folates, methionine and S-adenosylmethionine (SAMe). These have a really powerful impact on epigenetics.”

How Folates Affect Epigenetics

Folates are serotonin reuptake promoters. However, even if an individual is undermethylated and has a problem related to low serotonin activity, such as depression or anxiety, folates should not be given, Walsh warns. The reason? If you give folate, their methylation will improve and the patient will actually get worse.

The reason for this worsening is because, epigenetically, folates act as deacetylase inhibitors and sharply lower serotonin activity. Most autistic individuals will not have a serotonin problem and will thrive on methyl folate. However, an estimated 10 percent of autistic children and adults do have a serotonin issue and will severely regress if given methyl folate.

“We’ve had thousands of patients who were undermethylated depressives. I’ve seen more than 3,000 cases of clinical depression. I’ve got this huge database. The largest phenotype … is undermethylation.

But if you gave them any form of folate, they would get worse. Their methylation would improve, they would get worse, because it has a dramatic impact on serotonin reuptake. In contrast, methionine and SAMe are natural serotonin reuptake inhibitors.

They do essentially the same thing that Prozac and Paxil do. Folates have the opposite effect. Folates are wonderful if you want to knock dopamine level down in schizophrenics or people who have high anxiety — overmethylated people. It’s counterintuitive because folates are excellent methylating agents..”

To reiterate, some undermethylated people are intolerant to folates, and some overmethylated people thrive on folates even though folates improve methylation. As you can see, there are epigenetic complexities involved here, making self-diagnosis and self-treatment highly inadvisable.

It could be quite risky to take these bits and pieces of information and try to apply them on your own. There are simply too many variables. So, the bottom line here is to make sure you’re being treated by a certified walsh practitioner.

Why SSRIs Induce Violence

One major problem with SSRI antidepressants is the risk of self-harm and aggression as a side effect. Overmethylated, low-folate depressors are intolerant so SSRIs, and evidence suggests this genetic intolerance may have been a factor in many school shootings. Walsh, who has studied this phenomenon, notes 42 of the 50 major school shootings in the U.S. since 1990 were done by teens or young adults taking an SSRI.

“I discussed this … before the APA … I tried to explain to them that they … can do a blood test; they can find out which children or which adults are more likely to become violent if they get an SSRI. I’ve written about this several times; published it in magazines …

If you buy Prozac or Paxil, the insert inside warns that some people … are prone to suicidal or homicidal behavior. We now know which ones they are!”

How apple cider vinegar may assist overmethylators

This publication suggests that acetate, derived from acetic acid, may assist the brain and other organs in reducing inflammation. That it does so specifically by acetylating DNA histones, explains the effectiveness of products such as organic apple cider vinegar in managing overmethylators.

Overmethylators, who may be identified by a histamine blood test, would benefit because acetyl-CoA competes with methyl compounds at the DNA histone. Whichever molecule binds to the histones determines if the cell turns to the slow mode or fast mode. In other words, histone and methylation control the activation of the cell and the product of their DNA transcription to produce proteins.

In summary, apple cider vinegar’s affect on histones could be very good for overmethylators. And consequently it may not be so good for undermethylators. Inadequately nourished or supplemented overmethylators have a tendency manifest symptoms of verbosity, paranoia, phobias and at the further end of the scale auditory and delusional schizophrenia. Dr William Walsh PhD believes that as many as 46% of persons with schizophrenia are overmethylators.


Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression.

Soliman ML1, Rosenberger TA.

Author information


Acetate supplementation increases brain, heart, and liver acetyl-CoA levels and reduces lipopolysaccharide-induced neuroinflammation. Because intracellular acetyl-CoA can be used to alter histone acetylation-state, using Western blot analysis, we measured the temporal effect that acetate supplementation had on brain and liver histone acetylation following a single oral dose of glyceryl triacetate (6 g/kg). In parallel experiments, we measured the effect that acetate supplementation had on histone deacetylase (HDAC) and histone acetyltransferase (HAT) enzymic activities and the expression levels of HDAC class I and II enzymes using Western blot analysis. We found that acetate supplementation increased the acetylation-state of brain histone H4 at lysine 8 at 2 and 4 h, histone H4 at lysine 16 at 4 and 24 h, and histone H3 at lysine 9 at 4 h following treatment. No changes in other forms of brain or liver H3 and H4 acetylation-state were found at any post-treatment times measured. Enzymic HAT and HDAC assays on brain extracts showed that acetate supplementation had no effect on HAT activity, but significantly inhibited by 2-fold HDAC activity at 2 and 4 h post-treatment. Western blot analysis demonstrated that HDAC 2 levels were decreased at 4 h following treatment. Based on these results, we conclude that acetyl-CoA derived from acetate supplementation increases brain histone acetylation-state by reducing HDAC activity and expression.