Methylation 101

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Methylation 101

What is methylation?
Biochemically speaking, methylation is the process of adding or removing a methyl group – which is a single carbon attached to three hydrogens – to a molecule.  It is a simple chemical reaction that can totally alter the biology of a person – for better or worse – depending on where the methylation occurs.

Methyl groups are chemically inert, but adding them to a protein (the process of methylation) changes how that protein behaves in major ways.   Enzymes, hormones and genes are proteins and the process of methylation profoundly affects them all.   

Simply stated, the ability to transfer methyl groups in our cells (by adding or removing methyl groups as needed) equates to cellular adaptability.  In other words, a person who can methylate (or de-methylate) appropriately will be healthier because their cells are able to adapt to its constantly changing environment.  Methylation reactions are fundamental to human metabolism.  Examples include cellular detoxification, neurotransmitter synthesis, cell growth, tissue repair and gene expression.

Is methylation good?
Technically, methylation is neither inherently good nor bad – it is simply a process. Since enzymes act like switches for chemical reactions, methylation can ramp up enzyme function which is good in many (but not all) cases.  For example, methylation converts the toxic amino acid (homocysteine) into a beneficial amino acid (methionine). If your body cannot methylate properly, toxins build up in your bloodstream and will eventually cause disease.

But there is another side to the methylation story that is often overlooked, which is that you can over-methylate.  In susceptible people, hypermethylation has been linked to increased risk of cancer.  In a similar way that adding methyl groups to a protein can ramp up enzyme activity, this same process (methylation) affects our DNA and its resulting genetic expression.  In fact, methylation can turn genes on or off, which can be good or bad for our health, depending on the gene.

How do I improve my ability to methylate?
Fortunately, you can compensate for your body’s inability to methylate efficiently. This biological process is dependent on several B vitamins and mineral cofactors.  Some nutrients affect the process of methylation quite dramatically – methyl donors (nutrients like serine and choline) donate methyl groups to proteins and methylating factors (vitamin B12 and zinc) helps this process along by monitoring these reactions.  But if cells are already abundant in methyl-donor nutrients, you can “over-methylate.”

I’ve heard “over-methylating” may be linked to cancer?
Everyone has several genes that make what is called tumor suppressors, which do exactly what they sound like – they suppress tumor formation.  You want these genes to be switched “on”. Tumor suppressor genes make proteins that detect rogue cells, then reprogram these rogue cells to die via a process called apoptosis (programmed cell death).  We want tumor cells to die (so they don’t progress into cancerous tumors) so these genes are very important to our survival. 

Research suggests that hypermethylation of these tumor suppressor genes will turn them off.  This means an important cellular mechanism for protecting against cancer could potentially be inactivated by over-methylating.  So, prior to taking methylated supplements, it is very important to determine if you need them.

Hypermethylation versus Hypomethylation

Just like most systems in the body, both too much (hyper) or too little (hypo) of something is not good.  Both hypermethylation and hypomethylation have been associated with cancer. It is important to avoid excess and deficiency. This applies to food, hormones, nutrients, exercise, stress and…methylation.  Balance is key.   Just as too much of a one nutrient can potentially induce a deficiency in another – since biochemistry always works in balance – the process of methylation also works in balance. It is just as possible to over-supplement with methylated vitamins as to under-supplement.   The key is to supplement with exactly what your personal biochemistry needs.

If you are a hypo-methylator, you may benefit by taking nutrients that bolster methylation, including specific “methyl-donors” such as methylated folate.  However, if you are a hyper-methylator taking the same “methyl-donor” supplements when you are not deficient, it may potentially increase the risk of tumors.  This is a very new area of research that implies targeted supplementation is the key.

How do I optimize methylation without over-methylating?
Targeted repletion is the answer. Nutrient deficiencies are a major clue to how the body’s methylation systems are working.  For example, if you have cellular deficiencies in several B vitamins, have high homocysteine or deficiencies in minerals that serve as cofactors for methylation reactions (zinc, magnesium, selenium), repletion of deficient micronutrients can potentially improve systemic health quite dramatically.  Conversely, if you take these micronutrients when cellular reserves are sufficient, the potential for harm should be considered. Supplementing blindly (guessing what you need) can cause imbalance.  Balance is key. 

The solution…evaluate cell function, determine which micronutrients are deficient, then replete those specific deficiencies.  Measure – then correct – your functional cellular deficiencies.  

1. Measure (don’t guess) which nutrients in which you actually functionally deficient.

2. Correct (replete) your cellular deficiencies.

In doing so, your cell’s methylation process will automatically become more efficient and balanced.

References

1.Kulis M et al. DNA methylation and cancer. Adv Genet. 2010;70:27-56.
2.Esteller M et al. Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J Pathol. 2002 Jan;196(1):1-7.
3.Esteller M et al. A gene hypermethylation profile of human cancer. Cancer Res. 2001 Apr 15;61(8):3225-9.
4.Dulaimi E et al. Promoter hypermethylation profile of kidney cancer. Clin Cancer Res. 2004 Jun 15;10(12 Pt 1):3972-9.
5.Makarla PB et al. Promoter hypermethylation profile of ovarian epithelial neoplasms. Clin Cancer Res. 2005 Aug 1;11(15):5365-9.
6.Kwong J et al. Promoter hypermethylation of multiple genes in nasopharyngeal carcinoma. Clin Cancer Res. 2002 Jan;8(1):131-7.
7.Kushwaha G et al. Hypomethylation coordinates antagonistically with hypermethylation in cancer development: a case study of leukemia. Hum Genomics 2016;10 Suppl 2:18.
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