This post originally appeared over at AIP Lifestyle.  I’m re-posting it below because it is such an important topic and one that I’m starting to address more in my practice.

What’s up with methylation and MTHFR?

By Ryah Nabielski, MS, RDN

You may have heard of methylation and MTHFR recently as the branch of medicine called nutrigenomics becomes more researched and understood.  Nutrigenomics is the study of how food and nutrients influences gene expression, or epigenetics.  This article will cover some basic information related to methylation.  Thank you to the ladies at AIP Lifestyle for inviting me to write this post.  This is the perfect venue to discuss methylation because there is growing evidence to link poor methylation with autoimmune conditions.  One reason may be that you need good methylation for a healthy immune system and white blood cell function.

In fact, poor methylation has been linked to a host of conditions including:

  • Elevated homocysteine, which is associated with heart disease and stroke
  • ADD, autism, bipolar and other mental disorders
  • Dementia and Alzheimer’s
  • Chronic fatigue and fibromyalgia
  • Infertility and miscarriage
  • Birth defects including spina bifida and cleft palate
  • Cancer
  • Autoimmune conditions
  • Low glutathione levels
  • Decreased ability for detoxification

For some, optimizing methylation may prove the missing link in recovery.

What is methylation?

A methyl group is a molecule composed of one carbon and three hydrogen atoms (CH3.)  Methylation is the process of adding a methyl group to a molecule. It is one of the most important chemical reactions in the body, occurring billions of times per second.

Methylation is crucial for making and maintaining DNA and influencing gene expression by “turning on” or “turning off” certain genes.  At the core of the methylation cycle is the conversion of methionine, a dietary amino acid, into homocycteine and back again.  Here are a few visuals of the entire cycle for the biochemistry buffs out there.

Methylation is highly dependent upon good B vitamin status.  The important B vitamins involved in methylation are:

  • Folate/vitamin B9 (not to be confused with folic acid, a synthetic vitamin that acts differently in the body)
  • Vitamin B12
  • Vitamin B6
  • Vitamin B2

A deficiency in any one of these B vitamins can impact the body’s ability to methylate properly.

Besides nutrient deficiencies, methylation may also decrease because of a variation in the MTHFR gene.  MTHFR stands for methylenetetrahydrofolate reductase, which is a key enzyme in the methylation pathway (converting 5, 10 methylenetetrahydrofolate to 5 methyltetrahydrofolate.)  This enzyme, like all others, is coded for in the DNA.  One small change in that code is called a SNP, or single nucleotide polymorphism.  A MTHFR SNP can decrease the function of this enzyme, and therefore the body’s ability to methylate.  There are 23 known variants to the MTHFR gene.  Two of the variants are well understood and tested for (C677T and A1298C.)

MTHFR is just the tip of the iceberg when it comes to methylation. There are a lot of enzymes in the methylation pathway, and therefore many possible SNPs that could potentially cause issues.

We now have the ability to sequence DNA and this information allows us to use nutrition in a whole new way, to find the best support for each individual.

People with SNPs in the methylation pathway may require a higher (and sometimes lower) level of certain nutrients to achieve optimal health.

What you can do:

Here is the good news: you are in control of your genes!  They don’t control you.  We are learning more and more about how to influence gene expression.  Remember that gene expression is, at least partially, controlled by methylation.

Why do some people with the genetic marker for Celiac disease or breast cancer get the disease and others with the same markers don’t?  Epigenetics might help to explain. This brings us back to the age-old debate of nature vs. nurture.  Nature is the genetics and nurture is our environment and lifestyle, which influence gene expression.  We can’t change our genetics, but we can influence our epigenetics through our lifestyle choices and nutrition.

The field of nutrigenomics is so new and we are just learning about all of the genetic variations and what that means for individual nutrition support.  It is important to remember that no supplement or treatment is going to substitute for a healthy diet and good lifestyle behaviors.

So, even if you have a SNP (or two) for MTHFR (as it is estimated almost half of the population does), you may not develop the diseases listed above.  Here are some things you can do to optimize methylation and favorably influence your epigenetics:

  • Eat a whole food/real food diet.
  • Choose organic plant and animal foods in order to minimize exposure to pesticides, GMOs, hormones and antibiotics.
  • Identify food sensitivities and remove those foods from your diet.
  • Avoid folic acid in fortified foods and supplements (Folate is the form of this vitamin naturally found in nature.)
  • Optimize micronutrient (vitamin and mineral) status.
  • Heal the gut and optimize stomach acid so you can digest and absorb the necessary nutrients for methylation.
  • Exercise.  Some preliminary evidence suggests that high intensity intervals may be the best for improving methylation.
  • Reduce and manage stress.
  • Avoid toxins in cleaning products, body care products, cookware and household materials.
  • Support detoxification with Epson salt baths and saunas.
  • Drink purified water.
  • Think positively about your health.

Supplementation of the key B vitamins in the active forms (5 methyltetrahydrofolate, methyl-cobalamin, pyridoxal 5-phosphate, riboflavin 5-phosphate) along with other methylation pathway intermediates may prove very beneficial, especially for those with MTHFR variants.

My advice for using supplements to support methylation is to start at a low dose and increase slowly.  Work with a practitioner who understands the complexity of the methylation pathway and can customize a protocol for you.


References and resources for further information:

Dr. Ben Lynch

Dr. Amy Yasko

Spectrocell Laboratories

Ballestar E. et al.  Epigenetic alterations in autoimmune disease.  Journal of Translational Medicine. 2011; 9(Suppl 2):I3.  Accessed October 13, 2013

Ronn, T et al.  A six month exercise intervention influence the genome-wide methylation pattern in human adipose tissue.  PLoS Genetics.  2013; 9(6): e1003572.  Accessed October 13, 2013.

Sang-Woon C and S Friso.  Epigenetics: A new bridge between nutrition and health.  Advances in Nutrition.  2012; 1: 8-16.  Accessed October 13, 2013.

Yasko, Amy.  Autism: Pathways to Recovery.  Bethel, Maine: Neurological Research Institute, 2009.  Electronic.