The topic of methylation has become more and more popular over the past few years. Methylation is a crucial biochemical process that is essential for the normal function of almost all of our body's systems. It helps repair our DNA on a daily basis and regulates homocysteine metabolism. In addition methylation is needed for detoxification and keep inflammation under control.
Methylation requires certain cofactors such as B vitamins. When we are deficient in certain B vitamins methylation breaks down and the results can be disastrous.
Reduced ability to methylate has been associated with:
Testing for Methylation
Complete blood count One of the first things I look at is the mean corpuscular volume (MCV). Simply looking at MCV can reveal if someone has a methylation problem. Large red blood cells (folate or vitamin B12 deficiency) or anemia can be a sign of impaired methylation.
Plasma Homocysteine Homocysteine is an amino acid produced as part of the body's methylation process. The metabolism of homocysteine is highly dependent on vitamin B12 folate and vitamin B6. Therefore deficiencies in any of these may be associated with elevated homocysteine levels.
Organic acid testing Organic acids are products of metabolism that can identify nutrient deficiencies that typically precede any abnormal findings on a CBC or a comprehensive metabolic panel. Methylmalonate (MMA) is a more specific test for a vitamin B12 insufficiency; an individual's levels may be elevated even if you have a normal serum vitamin B12 or homocysteine level. In addition formiminoglutamate (FIGLU) is a functional marker of folate insufficiency.
MTHFR SNP There are many practitioners using genomic testing these days. MTHFR which stands for methyltetrahydrofolate reductase is a key enzyme in the methylation pathway. One small change in that code is called a single nucleotide polymorphism or SNP. A MTHFR SNP can decrease the function of this enzyme. The two main variants that are well understood and tested for are C677T and A1298C.
Supplements to consider
It is important to note that there are many patients with MTHFR SNPs that do not have an elevated homocysteine level. Most people with MTHFR may benefit from supplementing with separate folate (1mg or 5mg L-5-MTHF) if they do require higher dosing. The folate needs of individuals with MTHFR can vary quite of bit from patient to patient so there will not be one perfect product for all of them. How impaired the methylation is will be determined by examining if the patient has a heterozygous homozygous or compound presentation. One patient may have a heterozygous SNP and only need 1mg of L-5-MTHF while another may have a homozygous C677T and need 5-10 mg. Yet another patient may have one copy of A1298T and not need any additional folate. Keep in mind that some of these patients have developed compensatory ways to counter the SNP and may have sufficient folate.
When supporting methylation pathways it is important consider synergistic nutrients in addition to folate and vitamin B12. Some of the toughest patients will not get effective lowering of homocysteine until choline is supplemented. Choline converts to betaine with the help of riboflavin and aids methylation in this step of the pathway. In addition TMG (trimethylglycine) provides extra methyl groups. The most common block in the homocysteine pathway is the conversion of cystathionine to cysteine which requires B6 to activate the cystathionine beta-synthase enzyme. Serine is also needed along with vitamin B6 to help convert homocysteine into cystathionine.
Any roadblock in this pathway can cause homocysteine to elevate. When we intricately study the biochemistry of the homocysteine pathway we can see that it involves a series of conversions that require enzymes. Several nutrients especially B vitamins are needed for these conversions to occur. Keep in mind that stress as well as many medications can deplete B vitamins.
By Dr. Michael Jurgelewicz
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