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Methylation and You, some basic and applied science

Several times a day, I find myself discussing chemistry and currency with my patients. The chemistry part is to describe what comprises a methyl group: a carbon atom with three atoms of hydrogen attached to it. And though I know nothing really about economics, I do understand that methyl groups are the currency used for transactions in numerous parts of our physiology. Different substances (molecules, enzymes, proteins) receive a methyl group from another substance, a methyl “donor”, and become methylated. That methylated substance is able to travel elsewhere to a third substance in need of a methyl group, hand it off, and return “home” to await another methyl group from another donor. Think of a chain of folks ferrying a bucket of water to put out a fire, only in our bodies we have to have the chain – there is no option for the guy standing at the river to just take the bucket and run to the fire. There is also a separate route for the empty bucket to get back to the guy at the head of the chain.

Okay, that’s the basic process of methylation and its use as currency, but what makes it much more complicated and interesting in human physiology is that we have many interacting cycles of methylation. Methionine, for instance, which we absorb in abundance from protein sources in the diet, has extra methyl available which it hands off, degrading itself to homocysteine, which must receive a methyl group and transform back to methionine. Homocysteine receives the methyl group from methyl folate (from the diet or from supplements), which de-methylates to tetrahydrofolate, which then looks to pick up a methyl group so it can hand one off again to another homocysteine molecule.

There are four major methylation cycles, each one with side chains and/or internal short cuts, all of which work in harmony when supplied with a well-balanced diet and – this is the key part – healthy enzymes supporting the whole process along the way. Enzymes are proteins that our bodies make under the direction of our individual DNA. There are many, many enzymes related to these methylation cycles, and we have some understanding of about two dozen of them. What we now understand is that about a third of us have some significant defects in producing one or more of the enzymes we need to keep our interlocking methylation cycles functioning smoothly.

We depend on our methylation cycles for many aspects of our health. Methyl groups turn our various genes on and off, process the chemicals or toxins to which we are exposed, build and metabolize our messenger hormones in the brain (neurotransmitters), build immune cells, repair broken DNA (before it becomes cancer), produce energy, repair and maintain the myelin sheaths in our nervous system, and in fact the membranes of cells throughout the body.

With so many processes involved, you can see why it comes up several times a day when I am talking to patients. When I am working with someone complaining of fatigue, weakness, neurological, mood, or sleep problems, I wonder about their methylation. When someone’s lab tests show me abnormal levels of homocysteine, or the involved B vitamins, or evidence of inflammation or toxic exposures, I wonder about methylation. When someone is not responding properly to a medical intervention (conventional medicine or otherwise), I wonder as well.

Wondering, of course, doesn’t help very much, so we need to look for some real information to guide any possible recommendations I might give. Remember I said that methylated folate, for example, can come from food or from supplements. Supplying the proper supplements depends on knowing the genetics of each person’s individual methylation cycles, knowledge about the supplements’ potential interactions, following the proper sequence, and careful communication and follow-up, as there is a bit of trial and error for each person.

Learning about individual genetics is best accomplished with a kit from, which analyzes all your raw genetic data, but 23andMe is legally limited to offering you only the ancestry information they learn from your genes. The raw data, however, can be accessed by other websites that can turn it into medical information, appearing in plain English ( or methylation and detoxification specific analysis that still needs a bit of working to be readily understandable ( Insurance does not pay for, but will pay for individual blood tests on some of the methylation genetics. Ironically, they will pay, with proper coding, for very expensive genetic tests that essentially combine finding the raw data from your saliva and making the interpretation, when it pertains to which drugs might be best suited for your individual make-up. Doesn’t give the best information if what you want is to balance your genetics with food and supplements.

Methylation’s neighborhood

Methylation is the key currency handoff, but it’s quite dependent on its surroundings. Each process requires “co-factors” which must be supplied by diet or supplements, including proper levels of certain B vitamins, zinc, magnesium, and more. Certain medications can influence, not always predictably, the vigor of methylation reactions. Oxidative stress, or other forms of environmental toxicity, impede the proper working of methylation cycles. For someone not interested in pursuing the genetic testing, they can enhance the environment in which their body’s methylation processes operate. Eating a well-balanced diet and identifying basic supplement needs can cover the nutrient co-factors that are important. Avoiding obvious environmental toxins (most of which amount to some sort of estrogen) and managing our lifestyles so we have adequate sleep and manage our stress will all combine to give our methylation reactions less work to do, and enable them to maintain normal at less expense.

Complicated, isn’t it?  I find it so, and put a lot of time into studying the general field and each individual patient’s methylation picture. What we in general know now is a lot more than we knew 5 years ago. And from medical research and clinical experience, I expect our learning curve to rise sharply: we will know a lot more 6 months from now than we do now! So stay tuned….