If you have spent a significant amount of time in the wellness space over the past few years, you have likely heard of MTHFR. I get tons of questions on the MTHFR mutation with an abbreviation that sounds like a curse word. But what the heck is it? Are the MTHFR mutation and eczema related? Do I need to get checked? Find the answers in the blog below.
What is MTHFR?
MTHFR stands for methylenetetrahydrofolate reductase which is an enzyme produced by the MTHFR gene. We all have the MTHFR gene, so when someone says “I have MTHFR” they are simply saying they are human. What they probably mean to say is “I have an MTHFR gene mutation or variant”.
Interestingly, the alternative medicine world calls it a mutation while traditional western medicine calls it a variant. Just one more divisive issue between the two worlds.
To understand what the MTHFR enzyme does and why it may be important for some diseases, we need to discuss two other topics: Methylation and Folic Acid
The term methylation also gets thrown around quite a bit by the wellness community. Methylation is a process of adding a methyl group (1 carbon atom and 3 hydrogen atoms) to another compound in our body. Our bodies have evolved an elaborate system that uses these simple methyl groups to turn on and off enzymes, to turn on and off genes, to build and repair cells, detox, and for hundreds of other processes in the body.
Certain diseases have been associated with either undermethylation (not enough methyl groups being added) or overmethylation (too many methyl groups added). Methylation is a powerful tool for our bodies as it can completely turn certain genes off or on. So even though you are born with specific genes (DNA) from your parents, those genes may or may not be expressed depending on their methylation status.
Epigenetics focuses on how genes are expressed rather than simply if they are present or not. Diet and nutrition are crucially important in the methylation process as we will discuss later. This is one of the ways our diet directly influences how our genes are acting. For example you may have a cancer prone gene, however it is kept turned off via a methylation process aided by specific foods (hello green leafy vegetables).
How does MTHFR affect Methylation?
The MTHFR gene and resulting enzyme are important methylating tools in our body. Specifically, they are involved in methylating folic acid. Most pregnant women in the world are aware of folic acid as an important compound for preventing neural tube defects in babies (spina bifida). Folic acid however is not a naturally occurring nutrient. It is a synthetic compound created in a lab and added to food or vitamins.
More importantly, our bodies can’t use folic acid until it is changed into its methylated form – termed folate. There are many forms of folate and many names used interchangeably:
- L-Methylfolate Calcium
- Levomefolic Acid
Methylated folate occurs naturally in certain foods. Just remember the 3 L’s. Leafy greens, Legumes, and Liver. In fact, the term “folic” is from the Latin word folium (which means leaf) because it was found in dark-green leafy vegetables (think foliage).
Why are we so concerned with methylated folate? To understand we need to discuss more chemistry. Methylated folate is needed to convert homocysteine to methionine, and then methionine is used to create the mac daddy of all methylaters – SAMe. – B vitamins are also crucial to this process. This is a complex process as seen in the diagram below.SAMe is one of the primary methylation tools in the body. If there is not enough methylated folate available to drive these reactions, homocysteine will begin to build up. Elevated homocysteine levels are associated with a number of conditions including:
- osteoporosis, which occurs when bones become weaker
- Parkinson’s disease, which is a disorder of the central nervous system
- multiple sclerosis, which is an autoimmune disease that attacks the spinal cord and the brain
- eclampsia, which is the onset of seizures caused due to high blood pressure
- aortic aneurysm, which occurs when an abnormal bulge develops in the aorta
- cardiovascular disease
- heart attack
- atherosclerosis, which is an arterial disease
- end-stage renal disease
- hypothyroidism, which is when the body is unable to produce thyroid hormones
- blood clots
- cognitive impairment
- inflammatory bowel disease
- polycystic ovary syndrome
If the MTHFR enzyme is not functioning correctly, then less folic acid is converted to methyl folate, and homocysteine can’t be turned into SAMe. The result is our bodies may undermethylate.
The MTHFR Mutation (Variant)
Somewhere around 40% of the population has a variation in the MTHFR gene. Genetic variants are known as Single Nucleotide Polymorphisms, or SNPs (pronounced “snips”), and they are the result of one base pair of the DNA being changed. So even though the MTHFR gene is 77,000 base pairs long, we are talking about 1 substitution out of 77,000. But this subtle change in base pairs of DNA causes a very slight alteration in the shape of the MTHFR enzyme that is created. That change in shape can change the function of the enzyme.
These variations(or mutations) are typically passed down from the parents although they could also occur spontaneously. The two most problematic mutations that can occur are C677T and A1298C, which denote the placement of the mutation on the gene. The most common forms of MTHFR mutation involve various combinations of these genes being passed on from each parent:
- Homozygous: the same gene passed on from both parents- can occur if both pass on the 677 mutation, or the 1298 mutation.
- Heterozygous: one parent passed on the 677 mutation or the 1298 mutation but the other parent passed on a normal gene.
- Compound Heterozygous: one parent passed on the 677 mutation and the other passed on the 1298 mutation.
- Other more advanced and rare mutations.
Depending on which type of mutation is present, the function of the MTHFR enzyme can vary between 30-70% of its normal function. This is where things get much more murky, as the presence of the mutation doesn’t always directly correlate with how dysfunctional the enzyme is. If the enzyme is underperforming however, folic acid may begin to build up, and homocysteine levels will begin to rise with the effects described above.
MTHFR Genetic Testing
Many labs around the country now test for mutations in the MTHFR gene. 23andme is one of the most popular ways to test for MTHFR mutation, however you will need to enter your raw data into another site to understand your MTHFR status. Many labs use saliva, other use blood tests and costs can vary wildly.
However, before you rush off to get tested, be aware of what you plan to do with the results. Once again, just because you have the mutation (especially if you are heterozygous) doesn’t mean it will lead to disease. In fact, most of the connection of disease to MTHFR mutations are only associations without evidence of a direct cause and effect.
Also, it’s probably much easier to just measure homocysteine levels as this is a pretty good marker of MTHFR enzyme function. Also, as I will explain below, even if you have a MTHFR mutation it can be managed with diet. Once again, many of our inherited genetic diseases can be managed by diet – how many times can I say this!
MTHFR Mutation and Eczema – Is There a Connection?
I am routinely asked in my Eczema Transformation Program whether an MTHFR mutation and eczema could be related. Let me start by saying there is currently no clear evidence that MTHFR gene mutation leads to eczema. In fact, there have been just as many studies showing autoimmune diseases like eczema are caused by overmethylation rather than undermethylation (remember MTHFR mutation causes undermethylation).
Interestingly, high folate levels in moms during pregnancy have been associated with higher levels of allergic autoimmune diseases in kids. Those studies also showed no connection with MTHFR mutation. One study from 2013 showed an association with the C677T mutation and the development of eczema in kids, but only if their folate level was high – which just raises questions. These same kids had no elevation of homocysteine that would be expected if MTHFR was under performing. Lots of questions, few answers.
There is some evidence pointing to a connection between MTHFR mutation and general increase in inflammation. This would make sense from an eczema perspective, as childhood autoimmune diseases tend to be the result of excessive inflammation from a number of factors. Thus, the MTHFR mutation may just be one more factor contributing to the inflammatory bucket which begins to overflow and lead to conditions such as eczema. But it is definitely not the big smoking gun we are looking for to solve the eczema riddle.
Managing MTHFR Mutation
Interestingly, whether you have an MTHFR mutation or not, my recommendations below are the same. And ironically, they are the same things I have been preaching for years.
1. Consume more folate and B vitamins
Simply increasing the amount of methyl folate and b vitamins in your diet is one of the simplest ways to manage this problem. As we discussed above methyl folate if found in leafy green vegetables and others (spinach, asparagus, romaine lettuce, turnip greens, mustard greens, collard greens, cauliflower, broccoli, parsley, kale).
Legumes (beans) and lentils are also a great source of methylfolate. Finally, though not very popular in the US, are beef liver products (livermush, liverwurst, patte).
If you are unable to get your leafy greens, I love this supplement from Pure Encapsulations. It’s loaded with methylated folate and B vitamins to power methylation in our body. (For adults and kids 12 and older)
2. Focus on Gut Health
If the body is unable to absorb the nutrients stated above, no amount of spinach will solve the problem. Processed food chemicals, excess sugar, and environmental toxins all lead to gut damage and the result is a leaky gut and problems with absorption of nutrients. I have written several other blogs on this topic so check those out for more info.
- Promote a healthy microbiome by eating fermented foods like kimchi, kefir, miso, and kombucha, which help to maintain high levels of healthy bacteria in our gut and aid in digestion.
- Reduce intake of inflammatory foods such as sugar, gluten, refined grains, trans fats, and conventional dairy.
- Eat more healthy fats. N-butyrate, an anti-inflammatory short-chain fatty acid, helps feed the cells that line the gut and help them heal. You can get n-butyrate in the form of ghee or coconut oil.
- Consume other gut-friendly foods, including bone broth, organic vegetables and fruit rich in prebiotic fiber, and flaxseeds and chia seeds. Bottom line – Eat more plant points!
3. Avoid food and supplements with added Folic Acid
If possible, we want to focus on folate sources that have already been methylated so we don’t need to rely on the MTHFR enzyme. Also, many experts believe that synthetic folic acid can build up in our bodies and become toxic. I would recommend pregnant women use methylfolate supplementation rather than folic acid.
Also, check any supplements you or your child may be already taking to avoid synthetic folic acid. You can check out My Online Store for cleaner supplements.
4. Manage Stress
The folate pathway and methylation are also crucial for neurotransmitter production like serotonin, dopamine, and GABA. Persistent stress can actually cripple the bodies ability to methylate as well. Moving outside, yoga, meditation, journaling, reducing screen time, and exercise can provide dramatic reductions in stress.
5. Reduce Environmental Toxins and Improve Detoxification
The methylation system plays an important role in removing toxins from our body. If the toxic load in our bodies is reduced, less stress is put on our system. Removing toxins like plastics, chemicals in household cleaners, and scented candles which all release harmful substances. My family uses the AirDoctor and lots of indoor plants to improve air quality. Come shop with me at local stores like Costco, Walmart, and Target where I select non toxic products for your home.
Honing our bodies’ elimination techniques will also aid in detoxing from these harmful chemicals. Pooping everyday, sweating, some fasting, and epsom salt baths are all ways to detox from everyday toxins.
If you would like more information on MTHFR mutation and the biology behind it, check out Dr Ben Lynch, a naturopath who has studied this problem at length.
In Good Health,
Drs. Ana-Maria and John Temple, MD