NB: This article was modified March, 2024.
I’m offering a new course on this topic.
Justin (not his real name), came to see me with issues of panic attacks, obsessive thoughts, and the start of learning issues. He had started at a top university and found that he lacked focus. He had had this problem before, but found that he could not focus. A psychiatrist had given him Paxil to help calm him down, but that made the problem worse. Justin came to see me for neurofeedback. In doing the intake, I learned he lacked seasonal allergies and had severe sleep issues. He found that if he took an anti-histamine for any reason, he would become extremely agitated. Blood testing showed that Justin was overmethylated and methylated folate was key to treatment.
Overmethylation leads to a problem in the body called histapenia, meaning too little histamine. It is one subtype described by William Walsh in the Walsh Protocol. While similarities exist for the same diagnosis, overmethylation has peculiar traits. Patients with histapenia have a different presentation. They may be depressed, anxious, or unable to concentrate.
You might wonder, how is this different?
The quality to the depression, anxiety, or ADD is different in overmethylated people. Only 8% of the total population present overmethylated. But over 2/3s of Americans with a mental or behavior health problem have methylation problems. Depression, anxiety, schizophrenia, ADD, and behavior problems arise from overmethylation or undermethylation. In another article, I discussed undermethylation. In this one, I want to explore the traits, qualities, and treatment of overmethylation.
What Does Methylation Do?
Before jumping into overmethylation and its treatment, let’s review methylation. (My course goes into great detail about this topic.) Methylation is a process that allows for cells to turn DNA on and off. DNA is a complex molecule that needs to unwind to be used. There is a huge amount of DNA relative to the size of a cell nucleus. Stretched in one line, DNA reaches about 3 meters. That’s a lot of DNA to fit inside the nucleus, about 6 micrometers in diameter on average. That’s a decimal point followed by 6 zeros and then a 6 meters.
How does the cell get something that is 3 meters inside of something that is .0000006 meters in diameter?
The DNA wraps itself around proteins called histones. It becomes a small ball of thread that must be unwrapped for use. If the cell does the same thing repeatedly, it bookmarks the place that it frequently uses. Methylation is one method that cells bookmark DNA sections.
There’s a curious feature about this bookmarking. For many years, scientists believed our DNA dictated every trait and feature. The human genome project existed to map the entire sequence of human DNA. They expected over 100,000 genes in the human genome. The assumption was that there are specific sections of DNA that code for specific functions. But there were less than 24,000 found.
Why the discrepancy?
It turns out that cells transfer the bookmarks across generations. This is called Epigenetics, which is the science of understanding why genes turn on and off as they do. Cells use DNA adaptively. Genes turn on when the situation calls for it. Experiences shape what genes are more likely to be used. If the cell has a learned behavior, it is more likely to want to reuse that gene in the future. What you eat, breathe, think, and experience changes how your DNA turns on and off. Moreover, what your parents and grandparents ate, breathed, thought, and experienced is affecting your DNA today. Therefore, so many traits appear to be both learned and “genetic”. Through epigenetics, the DNA encodes the learned traits.
How Do I Know I’m Overmethylated?
Methylation is only one tag that is used by DNA. It is one that we can measure. And it is likely that through supplementation and diet, we change it. Through histamine, we can measure it indirectly. Histamine appears to move inversely to methylation. As methylation goes up, histamine comes down and vice versa. As we already discussed, many medications can affect histamine. This skews the test giving false positives or negatives depending on the result.
Sometimes going off of symptoms can be enough. This is tricky though, as even experienced practitioners have been mistaken. Below is a list of the symptoms that are frequently seen with overmethylation. Not all exist in the same person.
Another test we have is the plasma methylation test. This looks at the components of the methylation cycle, methionine, SAMe, SAH, and homocysteine. Based on the values of these, we can interpret what is happening in the methylation for a person. But it too can be affected by different things in the diet, medication, and so forth.
If I can’t test for it, then what?
Sometimes, doctors can predict a diagnosis based on a patient’s reaction to medications. Many overmethylated people will feel much worse taking an SSRI such as Paxil, Prozac, Welbutrin or other. These drugs lower histamine and raise serotonin, increasing the imbalance in the overmethylated. Overmethylated people often do better on benzodiazepines, such as Xanax and Ativan. I have had patients take both SSRIs and benzos and either do poorly or well on both. This is part of the reason I like to test.
The key feature I look for in overmethylation is someone who has blunted emotion. They may have a high pain threshold, and may need to feel pain to feel alive. Or they could be thrill seekers, needing to feel close to death to feel alive. But the basis of this is a hyper-stimulation inside. It’s as if they have emotional tetany. Everything is so intense that it all locks up. These people will need treatment their entire life. (As an aside, MTHFR changes are not predictive of Overmethylation.) Regardless, treatment is straightforward.
How do I Treat Histapenia?
Treatment is simple. Folate is the key. Overmethylation disorder is also called Low-Folate disorder. (It can be ADHD/ADD, OCD, depression, Conduct Disorder, anxiety, schizophrenia or something else too.) Folate is an important part of the methylation cycle. The key point to remember is that folate, even methyl-folate, is a net methyl reducer. In fact, in an otherwise healthy person, too much folate (methyl or otherwise) can shut off the methylation cycle and reduce methylation. Reducing methyl is key because that will cause histamine to increase. Histamine is an important messenger and neurotransmitter in the body. We usually think of it relative to allergies, but it is crucial for proper nervous system function. And folate changes the methylation equation. (Folinic acid and tetrahydrofolate are used in other processes in the body, including nucleotide synthesizes. I go through some of this and the rate-limiting steps in the liver in my course.)
Other vitamins are important to support the body. Niacinamide, Vitamin C, Vitamin B-6, and zinc are all important in helping balance methylation, and directing folate to be used appropriately in the body. Some patients find a small amount of manganese can be useful too.
When treating patients who are overmethylators, I see anxiety may increase for 1-2 weeks after starting the regimen, but then should improve. As with the other Walsh Protocol components, I highly recommend clinical supervision. A qualified professional will assist if anything unexpected arises. And there are many people who have assumed that they have one condition subtype, but may have multiple imbalances.
While different studies estimate around 37% of schizophrenics are low-folate, overmethylation in the general population is rare. The numbers are likely dropping because of folate enriched foods. (There are potentially other risks associated with this approach.) Treatment is simple if the diagnosis is correct. Most people find they improve with treatment. Some have other imbalances that need further treatment.
To learn more about methylation, check out my webinar. Or if you have any of the conditions listed above, please reach out to get tested. I can help you find if there is an imbalance that can be treated.
