Methylation – An Evolving Front

When I first got interested in nutritional medicine several years ago, there was a fair bit of talk about homocysteine and how studies such as this suggest that there may well be a linear association between accumulation of homocysteine in the system, and risk of heart disease, stroke and other chronic degenerative diseases. However subsequent studies didn’t show a consistent beneficial effect of homocysteine-lowering therapies on mortality outcomes.


More recent information on methylation may have shown some light upon this area, and why despite the positive association with disease, homocysteine-lowering hasn’t been particularly successful as a treatment. The nutrients that were used have mainly been synthetic folic acid and B12. Sometimes B6 was used as well.


Firstly, what is homocysteine? From all reports, it is an amino acid derivative, formed in the body from a methyl group being stripped off the amino acid methionine. It gets reformed into methionine by having a methyl group added onto it. Some people call this the methylation “cycle” as methionine is continously being stripped into homocysteine and then reformed back into methionine in the body.
Methyl groups are probably the most basic structural group in organic chemistry and basically consist of one group atom bonded to three hydrogen atoms. Chemically they are often written as CH3. Recent studies have shown that methyl groups may also have an important role in ageing, detoxification and mental health.


Why is this important? It appears that methylation reactions in the body are often impaired with many chronic degenerative diseases and those with poorer health in general. For instance this recent study suggested that those older men with poorer health generally had elevated homocysteine levels. So a reasonable assumption is that methylation is impaired in these patients, leading to accelerated ageing, poorer detoxification of metabolites in the body and less methyl groups available for keeping the nervous system healthy.


There are many ways you can measure methylation. The homocysteine test is probably a fairly crude measure, however a whole blood histamine has been studied by the Walsh Research Institute to predict the subtypes of those with mental illness who can benefit from methyl-donor therapy. Another way is to trial using a supplement such as TMG at a dosage of 1000mg to 2000mg daily for around 3-4 weeks and observe for signs of increased energy or mental alertness. It appears some people, a minority in countries such as Australia, may however have overactivity of certain parts of the methyl cycle and can be considered “overmethylators”. In these patients caution is needed with giving any methyl donor, but particularly TMG or the universyl methyl donor, S-adenosylmethionine (SAMe).


Assessing and addressing methylation so far has produced quite impressive results in my practice. In my next blog I’ll talk a little about how methylation seems to be vital for rebuilding the protein molecule glutathione and also for heavy metal detoxification.


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