What is MTHFR?

At first glance your brain starts to fill in other letters and you probably arrived at a "dirty word" but that's not what I'm talking about. It's actually a genetic mutation that is gaining popularity.

MTHFR is an abbreviation for mthylenetetrahydrofolate reductase. Try saying that three times fast. MTHFR is an enzyme that is responsible for some important biochemical processes in your body. It converts B9 (folate) into methyl-folate which is essential for a process called methylation.

MTHFR is getting attention due to a genetic mutation that may lead to high levels of homocysteine in the blood and low levels of folate and other vitamins (primarily Vitamin B12).

Due to the increased levels of homocysteine and symptoms associated with having too much homocysteine in the blood stream, there's been some health concerns and testing has become mainstream for the MTHFR gene.

What is Methylation?

Methylation is the adding and removing of a methyl group (CH3) to amino acids, DNA, and other enzymes or proteins. Most of our biological molecules are chains of hydrocarbons — carbons plus hydrogens. So adding a methyl group stacks on one more link in a hydrocarbon chain.

Adding a methyl group – or an extra carbon plus three hydrogens – then changes the original molecule into something different. For example, a methyl group is added to serotonin in the conversion to melatonin.

Methylation can turn on and off genes, maintain and repair your DNA, and alter proteins. It is important in the nervous system in the production and breakdown of neurotransmitters and in the detoxification of some environmental toxicants.

The methylation cycle is also intimately involved in heart health. It controls the level of homocysteine, an important marker of heart disease risk. It is also involved in cholesterol levels, and genetic variants in the methylation pathway have been linked to heart disease in many studies. Additionally, the pathway is involved in regulating hormones, such as estrogen, as well as playing a role in histamine levels.

Genetic variants can change how well a piece of the methylation pathway works. Knowing where you have genetic variations can help you understand what you need to do to get around the slow-downs in the methylation pathway.

Why is Methylation So Important?

Every single cell and tissue in your body undergoes and experiences methylation. Methylation helps to repair cells that have been damaged and optimize DNA cell function. One of the primary functions of methylation is to turn homocysteine into methionine. Why is this so important you ask? Methionine produces glutathione, which is your body's most potent detoxifier. Methionine also helps to build proteins, repair cells, supports necessary inflammatory response, and helps the liver process fats.

Lower levels of glutathione have been linked to autoimmunity and cancer. This also supports that there may be a connection between the genetic mutation of MTHFR and these serious health conditions.

Let's take a closer look. MTHFR is involved in a series of chemical reactions necessary for your body to properly use folate (vitamin B9) and, as part of a multistep chemical sequence, transforms a by-product of this process, homocysteine, which has been associated with intravascular inflammation and most of the medical problems associated with MTHFR SNPs, into the amino acid methionine, an important building block in protein formation and required for the formation of S-adenosylmethionine (SAM-E), a universal methyl donor for almost 100 different substrates, including DNA, RNA, hormones, proteins, and lipids.

Think of the methylation pathway as a light switch. Sometimes we want to turn things on and sometimes we want to turn things off. Methylation is responsible for this genetic expression of turning on or off different biochemical processes.

The problem arises when a genetic expression turns on and leaves on something that should be turned off or vice versa when something that is off should be turned on. When this happens the consequences can be serious. For example, we have cells that are programmed to die every second of each day. This is called apoptosis (programmed cell death). We need this to happen. It's our bodies way cleaning and pruning old cells and not letting things get out of hand. So if the sequences in this process are altered, damaged cells may, instead of automatically self-destructing as they are supposed to, they continue to replicate. Another term for excessively replicating damaged cells? Cancer. Which is why MTHFR SNPs are associated with possible increased risk of cancer.

Further, properly functioning MTHFR is also necessary for the utilization of vitamin B12, and MTHFR SNPs have been associated with vitamin B12 deficiency. Vitamin B12 is required for proper red blood cell formation, neurological function, and DNA synthesis.

Variations of the MTHFR Mutation

The MTHFR gene is one of the 20,000 genes in the human body. It is the "instructions" for the creation of the MTHFR enzyme. While there are about 40 variations in the MTHFR gene, the two that carry the most significance towards human health and potential are the A1298C and C677T variations. These variations are referred to as SNPs (pronounced 'snips'), which is short for single nucleotide polymorphisms.

About 50% of the US population carries at least one SNP. People can have either one or two mutations (or neither) on the MTHFR gene. A SNP is a part of the DNA of a gene that is commonly different (or varies) from person to person.

The two most common MTHFR SNPs studied are the C677T and the A1298C. The letters and numbers indicate the mutations appearance and location on the gene.

C677T. Some 30 to 40 percent of the American population may have a mutation at gene position C677T. Some 25 percent of people of Hispanic descent, and 10 to 15 percent of Caucasian descent are homozygous (have two mutations) for this variant.

A1298C. Around 20 percent of the American population may have a homozygous mutation at gene position A1298C. It’s also possible to acquire both C677T and A1298C mutations (one copy of each).

Gene mutations are inherited, which means you acquire them from your parents. At conception, you receive one copy of the MTHFR gene from each parent. If both have mutations, your risk is higher of having a homozygous mutation.

Symptoms Associated With The MTHFR Mutation

Having one variant (heterozygous) is unlikely to contribute to health issues. Some people believe having two mutations (homozygous) may lead to more serious problems. There are two variants (forms) of mutations that can occur on the MTHFR gene. The more mutations you have, the less the MTHFR enzyme is able to do its job. When you decrease your ability to methylate, there is a greater risk for health concerns. Below is a list of conditions that have been associated with the mutation of the MTHFR gene:

  • Depression

  • Digestive Issues (IBS, IBD)

  • Bipolar disorder

  • Anxiety

  • Schizophrenia

  • Acute leukemia

  • Colon cancer

  • Cardiovascular and thromboembolic disorders (stroke, heart attacks, heart disease)

  • Chronic pain and fatigue

  • Migraines

  • Recurrent miscarriages in people of child-bearing age

  • Pregnancies with neural tube defects

Testing for the MTHFR Mutation. Should you test?

Conventional testing is readily available for the MTHFR SNPs themselves, and also for plasma homocysteine, B12, and folate levels. Any licensed provider can order these for you – though they are not necessarily all covered by insurance. Independent labs such as Genova and Doctor’s Data also offer these labs; I recommend reviewing your results with a knowledgeable Functional Medicine Practitioner before jumping to scary conclusions or jumping onto the high dose supplement bandwagon.

However, it’s very important to remember that the presence of an MTHFR SNP does not mean you are automatically at risk for any of the symptoms or conditions I’ve mentioned, and does not automatically mean you need supplementation to offset the potential risks. That’s all they are: potential risks. The presence of the gene alone doesn’t mean that the enzyme won’t function well. It can’t tell whether you personally are methylating well or poorly, for example, and whether you personally need additional support. And in fact, excess supplementation has it’s own risks!

So you’ve gotten tested and discovered that you have an MTHFR SNP and now you wonder what you should do. First – don’t panic! For one, just having the SNP doesn’t portend gloom or doom, and if you do have the SNP there are things you can do to protect your health.

Essentially, if you have the MTHFR SNP, you can’t get your folate into its methylated form, because your methylation pathway isn’t working, and then you can’t recycle your homocysteine back into methionine. It’s a bit like you need to get from Train Station A to Train Station C, but Station B is out of order. You need to hop a cab to get around the obstacle. Methylfolate is an already methylated form that allows you to bridge the gap without the functioning enzyme. From there, the rest usually takes care of itself.

Final Thoughts

Although your genetic code cannot be rewritten, you do have a tremendous amount of control as to how your genes are expressed. Your diet and lifestyle play a HUGE role in how your genes affect your health.

Geneticists have an expression: nature loads the gun, environment pulls the trigger. While having the MTHFR SNP may in itself inherently pose some risks that require you to supplement with methylfolate and methylB12, it’s important to also remember that just having the gene doesn’t necessarily increase your risks over the next person who doesn’t, and that we’re all at risk due to the overwhelming number of environmental toxins we’re facing in the setting of overall nutrient depleted diets. Skipping meals, skimping on veggies, and not getting enough phytochemicals in our diets, while also not getting enough sleep and being under enormous stress and chronic overwhelm put us at just as much risk if not more, of health problems. And if you do have a genetic risk, you’ve got a double whammy.

So regardless of our MTHFR status, we all need to be mindful of supporting our elimination and detoxification pathways, avoiding the toxin exposures within our control in our diets, households, and body products, and leading healthful, mindful lives. Adding in a multivitamin with methylfolate, or supplementing a modest amount daily, is a safe and appropriate strategy even if you’re unable to get any testing and want to maximize your health protection.



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