- The MTHFR gene 101
- Common MTHFR gene variants
- Reported MTHFR “Symptoms”
- MTHFR and cardiovascular disease
- Is the hype surrounding MTHFR variants justified?
- When do MTHFR variants affect our health?
- Homocysteine and B vitamins
- Should you get checked for a MTHFR gene variant?
Perhaps you’ve learned you carry an MTHFR gene “mutation” and are worried because you’ve heard about all the associated symptoms health conditions.
Well, you can rest easy because there is no such thing as MTHFR “symptoms.” The numerous articles published online that claim otherwise are doing the public a disservice by preying on people’s health concerns, often to sell supplements.
Now, this isn’t to say that MTHFR polymorphisms don’t play a role in health, because they can. However, MTHFR is only one gene in 30,000 in the human genome, and the role it plays is overstated in many functional health circles. There is a large contrast between “single gene” conditions, like cystic fibrosis, and genes that may affect health in concert with many others. MTHFR is the latter, we can’t pin a single health condition on MTHFR polymorphisms, standing alone, period.
This means having MTHFR symptoms is impossible.
The MTHFR gene 101
MTHFR gene codes for the methylenetetrahydrofolate reductase enzyme which has a key role in breaking down the amino acid homocysteine. Homocysteine levels can run high when methylenetetrahydrofolate reductase enzyme activity gets too low. In cases of elevated homocysteine, MTHFR variants plus poor diet are often to blame.
We all carry two copies of MTHFR genes, one from your father and one from your mother. The section of the DNA code that varies is called a “variant,” and MTHFR variants are very common.
Because every human alive has MTHFR genes, and because of the widespread prevalence of the much Googled variants, you needn’t worry about MTHFR “symptoms.”
Common MTHFR gene variants
Two main MTHFR gene variants are currently being studied:
These variants are surprisingly common. It has been estimated that in America, about 25% of Hispanics and 10-15% of Caucasians carry two copies of C677T variant. When someone carries to copies of an MTHFR variant, or any other genetic variant for that matter, they are said to have a homozygous “mutation.” By contrast, those who carry only one copy of a variant are said to have a heterozygous “mutation.”
For the general population, it is estimated that 30% of people carry at least one copy of either MTHFR C677T and A1298C. These genetic variants are very common, which is why it is impossible to have “MTHFR symptoms.”
The one exception here is the Black community. As we discussed in our piece on the health impact of MTHFR, because MTHFR variants are much more rare in the Black community, testing is all that much more important. However, even though MTHFR variants are seen with less frequency in the Black community, there is still no evidence that, standing alone, they cause symptoms.
Reported MTHFR “Symptoms”
A quick Google search reveals the following as symptoms supposedly linked to the MTHFR gene:
- cardiovascular and thromboembolic diseases (specifically blood clots, stroke, embolism, and heart attacks)
- bipolar disorder
- colon cancer
- acute leukemia
- chronic pain and fatigue
- nerve pain
- recurrent miscarriages in women of child-bearing age
- pregnancies with neural tube defects, like spina bifida and anencephaly
At Gene Food, we are surprised articles like this keep getting published and ranked in search engines. There is simply no way you can attribute long lists of health conditions, like the one above, to MTHFR variants that are present in 30% of the population.
The scientific evidence simply isn’t there to make these kinds of sweeping claims. For example, migraines, cardiovascular disease, and every other symptom on this list has a myriad of causes.
MTHFR and cardiovascular disease
There’s been a huge amount of interest in how variants in the MTHFR genes are linked to cardiovascular disease (CVD). A much cited meta-analysis looked at 19 studies, totaling 48,175 cases of coronary artery disease, to determine whether the presence of MTHFR variants increased the risk of heart disease2. Researchers did observe a moderate elevation in homocysteine, however, they found little to no effect on coronary artery disease risk.
MTHFR and heart disease in the Black community
The problem with this meta-analyses is that it contained only one study with African subjects. In that population, the risk for heart disease was increased by 63% in Black subjects who carried one copy of C677T.
Is the hype surrounding MTHFR variants justified?
No, it isn’t. However, if you’re homozygous for MTHFR variants, or for the Black community, if you carry one copy of C677T. In these cases, the end-result of the variant may be elevated homocysteine, and amino acid metabolite that can cause health issues when blood levels get too high.
If you’re heterozygous (one copy of either of the variants) for MTHFR, research has found that having a single copy of these variants does not decrease the activity of the enzyme and does not significantly affects homocysteine levels 3.
A study done was done to determine whether the presence of MTHFR variants in individuals affected the breakdown of homocysteine. What they found was that homocysteine levels in the blood were within the normal range.
This was an important finding because it suggests that an individual can be healthy even with a lower-than-normal level of enzyme activity, as long as there is enough to do its metabolic job of breaking down homocysteine and keeping it within range. That’s the reason why most people with these common variants wouldn’t even be aware of it without genetic testing, as there aren’t any notable symptoms.
When do MTHFR variants affect our health?
The best, scientifically vetted, condition we can tie to MTHFR is homocysteine.
This brings me to the MTHFR homozygotes that carry two copies of the C677T variant. These genotypes may be more likely to see elevated levels of homocysteine. It is important to note that, even in the presence of homozygous “mutations,” this enzyme still functions at some level.
You may be wondering what the symptoms of high homocysteine are?
Well, there usually aren’t any symptoms, and when reported they’re subtle and appear to vary from one person to the next. It’s a difficult condition to ‘pin down’ unless you specifically get your homocysteine levels checked through genetic testing or blood enzyme level analysis. Boston Heart Diagnostics runs homocysteine panels for participating physicians.
Although rare, it’s important to note that this condition may also develop if you don’t possess any MTHFR variants. Dietary deficiencies of folate, vitamin B6, and vitamin B12 specifically may lead to the development of hyperhomocysteinemia.
The diagnosis of vitamin B12 deficiencies is important since high dose folic acid supplements may mask B12 deficiencies that could lead to irreversible neurological symptoms.
The symptoms of folate or vitamin B deficiencies are much easier to detect since the symptoms are more pronounced:
- Pale skin
- Mood changes
- Tingling sensations in your hands or feet
- Mouth sores
These symptoms are easily reversed following the appropriate Vitamin B or folate supplementation.
Homocysteine and B vitamins
Because hyperhomocysteinemia (whether its caused by the presence of the variant or not) may be a risk factor for some diseases, research has suggested that the calibrated assumption of the correct doses of folic acid, vitamin B6, vitamin B12, and betaine may be highly beneficial in managing hyperhomocysteinemia-related conditions 5.
Treatment is therefore simple and straightforward. By increasing your folate intake via a supplement, this helps your body to bypass the need for the methylenetetrahydrofolate reductase enzyme that is produced by the MTHFR gene, which then reduces homocysteine levels.
So, remember; possessing one of these variants does not predispose you to any single disease. They are not life-threatening and mostly symptomless. If you’re still concerned, discuss this with your GP to test your blood homocysteine levels and determine what treatment and supplementation is best for you, where necessary.
Should you get checked for a MTHFR gene variant?
For the vast majority of the population with one of these variants, the overall risk associated with having the variant is very small since having them does not change treatment.
This is why it has been recommended by the American College of Medical Genetics and Genomics (ACMG) 4 not to test for the variants unless a person has very high homocysteine levels.
This is because high levels rarely result from having the common MTHFR variants alone, and the individual should be carefully evaluated for other factors known to affect homocysteine, such as:
- Low thyroid hormones (hypothyroidism)
- Advanced age
- Chronic conditions (obesity, diabetes, high cholesterol, physical inactivity, high blood pressure)
- Certain medications
If high levels of homocysteine cannot be explained by factors such as those listed above, a consultation with a genetics councilor may help identify whether you are homozygous for the MTHFR variant.