Key takeaways:
- The MTHFR enzyme converts folate (vitamin B9) to its active form, 5-MTHF.
- Folate is used to create methyl groups, which cells use to synthesize neurotransmitters, detoxify toxicants, methylate DNA, and maintain a healthy heart.
- The common MTHFR C677T and A1298C variants lower enzyme function (up to ~70–80% for C677T homozygous, ~20% for A1298C homozygous), especially when folate is limited.
- You don’t need expensive testing for MTHFR; you can check your C677T and A1298C SNPs in 23andMe, AncestryDNA, or similar raw data files.
- Optimizing your diet and nutrient intake to align with your genetic variants may help to improve overall wellness and healthy aging.
What is the MTHFR gene?
MTHFR is a central gene in the methylation cycle and is a limiting factor for producing methyl groups from folate (vitamin B9).
Specifically, the MTHFR gene codes for an enzyme called methylenetetrahydrofolate reductase that turns folate into the active form, 5-methyltetrahydrofolate. This enzyme, along with the active form of vitamin B12 (methylcobalamin), drives an essential portion of the methylation cycle.
Common genetic variants, called MTHFR C677T and A1298C, affect how the enzyme works and impact the availability of methyl groups.[ref] Genetic variants are variations in the DNA sequence that can influence the function of a gene or the protein it encodes.
Which DNA tests cover MTHFR?
You don’t need expensive or specialized testing to find out your MTHFR status. The MTHFR genetic variants are available in 23andMe and AncestryDNA raw data files, which are free to download if you’ve done a test with them.
Here’s a quick list of inexpensive testing options: 23andMe, AncestryDNA, Sequencing .com, TellMeGen, MyGene Food
In addition to understanding your MTHFR variants from your DNA raw data, consider testing your homocysteine levels to see what your current status is.
MTHFR: Key role in the methylation cycle
The MTHFR gene encodes an enzyme that is a key part of the methylation cycle.
Methylation is the addition and removal of a methyl group (-CH3) to amino acids, DNA, and other enzymes or proteins. Within the methylation cycle, folate can be used to donate a methyl group that is used by SAMe for methylation reactions. This is a cycle that also involves homocysteine (which we will come back to in a minute).
Related article: Methylation cycle report (MTHFR, COMT, B12, and more)
Methyl groups are used to:
- Form new molecules, including neurotransmitters
- Control DNA gene expression (turn on and off genes)
- Detoxify certain substances
Let’s look at each of these:
1. Forming new molecules:
Most of the molecules in our body are chains of hydrocarbons — carbons plus hydrogens. So adding a methyl group, a carbon plus three hydrogens, stacks on one more link to a hydrocarbon chain. The methyl group changes the original molecule into something different. A methyl group makes the molecule non-polar, which means that it isn’t able to mix with water and instead can pass through lipid membranes more easily.
Example: The synthesis of melatonin involves methylation
A methyl group is added to serotonin in the two-step process that forms melatonin.
2. DNA methylation:
DNA methylation is the addition of a methyl group to specific locations on a chromosome. By binding to these spots, methylation can turn genes on and off, and maintain and repair your DNA. This is an ongoing, essential, and continual use of methyl groups.
3. Detoxification and breaking down substances:
Methylation is essential in the nervous system, in the production and breakdown of neurotransmitters, and in detoxifying some specific environmental toxicants such as arsenic.
How does folate interact with the methylation cycle?
The folate and methylation cycle is a series of biochemical reactions that involve the transfer of methyl groups. For those who like a visual pathway, here’s what the complete folate and methylation cycle looks like. Notice that MTHFR is in a key spot, tying together 5-methyltetrahydrofolate and homocysteine in the cytosol of the cell.
When considering MTHFR within the folate cycle, it’s important to note that MTHFR is important in the conversion of folate in the cytosol of the cell, where it interacts with the remethylation of S-adenosylhomocysteine to homocysteine. Folate is also important in the mitochondria, but those folate-dependent reactions rely on SHMT and 1-formyl-THF instead of MTHFR and methylfolate.[ref]
The MTHFR C677T and A1298C variants:
Two common variants in the MTHFR gene, C677T and A1298C, cause the enzyme not to function normally. Let’s look at what this means and the implications for your health.
Understanding the terminology:
The MTHFR C677T variant is a single nucleotide polymorphism (SNP). A SNP is a variation in a single nucleotide base pair (the As, Cs, Gs, and Ts) that differs from the typical nucleotide at that spot in the gene for part of the population. Similarly, A1298C is another SNP in the MTHFR gene.
Both MTHFR C677T and MTHFR A1298C are common variants (SNPs). Both polymorphisms are found in approximately half the population. The substitution of a different nucleotide – the A instead of a G – makes the MTHFR enzyme function a little differently.
| Variant/SNP | Genotype | Enzyme function effect | Notes |
|---|---|---|---|
| C677T (rs1801133) | G/G | Typical | No major reduction in activity. |
| C677T (rs1801133) | A/G | ~35–40% decreased | Thermolabile enzyme; more sensitive to low folate. |
| C677T (rs1801133) | A/A | ~70–80% decreased | Strongest impact on folate-dependent methylation. |
| A1298C (rs1801131) | T/T | Typical | No major reduction. |
| A1298C (rs1801131) | G/T | Slightly decreased | Mild effect alone. |
| A1298C (rs1801131) | G/G | ~20% decreased | Moderate reduction. |
| Compound C677T + A1298C | A/G + G/T | ~50% decreased | One copy of each |
Let’s look at the details of what this means:
What is the impact of MTHFR C677T:
The MTHFR C677T variant changes the enzyme structure in a way that makes it break down faster at normal body temperature (more thermolabile). This faster enzyme breakdown then reduces the amount of enzyme available in each cell. This can be a problem when folate is limited.[ref][ref][ref]
- One copy of the C677T variant reduces enzyme function by about 35-40%.
- Two copies (homozygous) cause a ~70% reduction in enzyme function.
Why is it called C677T?
The variant involved in C677T is a change from Cytosine (C) to Thymine (T) at position 677. This variant was originally defined on the minus strand of the DNA, but most genetic raw data files report it on the plus strand. That is why in your genetic raw data, you will see G for the typical and A for the variant, but many research studies will still include C for the typical and T for the variant. Just remember that C=G and T=A.
What is the functional impact of A1298C?
The A1298C variant causes less of a change to the way the enzyme works, with two copies of the variant decreasing enzyme function by around 20%. [ref]
Compound heterozygous: MTHFR C677T + A1298C:
Having one copy of each variant, called compound heterozygous, reduces enzyme function by around 50%. You may be wondering about what happens if someone has two copies of each variant. That is a combination that is rarely, if ever, seen (likely incompatible with life).
Research studies on MTHFR C677T or A1298C variants:
Having an MTHFR variant increases the relative risk (not certainty!) of many chronic diseases, but this does not mean it will cause you to have that disease.
According to multiple meta-analyses, MTHFR C677T and A1298C increase the relative risk for high homocysteine, cardiovascular disease, stroke, neural tube defects, certain pregnancy issues, depression, migraines, and some neuropsychiatric conditions, especially with low folate/B vitamins.[ref] These same variants can lower the risk for certain conditions as well, illustrating tradeoffs of both positive and negative effects. Importantly, dietary changes or supplemental vitamins can eliminate many of the problems associated with the MTHFR variants.
The MTHFR gene is extremely well researched, with over 6,000 studies investigating the C677T variant. There is also a lot of misinformation and hype about MTHFR, so this article sticks just to the high-quality studies on the topic.
Studies show that the C667T and A1298C variants increase the relative risk:
- high homocysteine, stroke, and heart disease[ref][ref][ref][ref][ref]
- neural tube defects and cleft lip[ref]
- preeclampsia and hypertension in pregnancy[ref][ref]
- miscarriage[ref][ref]
- depression or anxiety[ref][ref][ref][ref][ref]
- Alzheimer’s and dementia (C677T only and small increase according to 2026 meta-analysis)[ref][ref]
- autism spectrum disorder (C677T only according to 2026 meta-analysis)[ref]
- rare problems with nitrous oxide[ref], but most have no problems[ref]
Let’s dig into the details of what research studies and clinical trials show.
Studies on MTHFR variants show:
1. Depression and the MTHFR Gene Variants: A1298C and C677T
- A meta-analysis of 26 studies found that the MTHFR C677T variant was associated with an increased risk of depression.[ref] Age and gender may also play a role here. Postmenopausal women who carried the C677T variant had a 2 to 3-fold increased risk of depression.[ref]
- Women with two copies of the A1298C variant were at twice the risk of major depressive disorder (MDD). The risk of MDD was even higher in people who also had COMT slow (MET) alleles. (read about COMT)[ref]
Not all studies agree, and some studies show that the MTHFR C677T variant has little to no impact on depression risk. The difference in study results could be due to diet. People who eat a diet that includes more folate (green vegetables, legumes, liver) may not be at an increased risk of mood disorders, while people who eat few folate-rich foods may be more susceptible to depression.[ref][ref]
Related article with more details: MTHFR: depression and anxiety
2. High Homocysteine with MTHFR variants:
The methylation cycle also controls the level of homocysteine, an important marker of heart disease risk. It is also involved in cholesterol levels.[ref] Genetic variants in the methylation pathway, including MTHFR, are strongly linked to high homocysteine levels and heart disease in many studies. For example, a study in acute coronary syndrome patients showed that MTHFR C677T increased severity as well as homocysteine levels. High homocysteine is also linked to increased blood clots.[ref][ref][ref][ref]
Related article: Homocysteine- Genetics and Solutions
3. Increased risk of heart disease
Studies show a link between MTHFR C677T and an increased risk of cardiovascular disease. For example, a meta-analysis found that two copies of the MTHFR C677T variant (A/A, homozygous) increase the relative risk of heart disease by 38%.[ref][ref] However, not all studies agree, and a large prospective study (n=6,000) found that older people with two copies of the C677T allele were at a 30% decreased risk of death from cardiovascular disease when other parameters were included.[ref]
The increased risk is not just due to high homocysteine. People with the C677T variant (AG or AA) have reduced endothelial function, even when homocysteine levels are normalized by increasing folate intake. The endothelium is the lining of blood vessels, and endothelial function controls how the blood vessels relax or contract to control blood pressure.[ref][ref]
Related article: MTHFR, riboflavin, and reducing high blood pressure
4. Pregnancy, infertility, and MTHFR:
One of the first researched links to MTHFR variants was neural tube defects in infants. Babies need folate for the spinal column to develop fully, and the MTHFR variants increase the risk of problems.[ref] This is why prenatal vitamins contain folate and why folic acid is added to white rice and white flour.
Related article: MTHFR, pregnancy, and infertility
5. Breakdown of estrogen, interaction with histamine:
Additionally, the methylation pathway involves the regulation of hormones, such as estrogen, and plays a role in histamine levels through breaking down high histamine.
Related article: Histamine metabolism and estrogen receptors
6. Migraines
Numerous studies show that MTHFR variants are linked to a significantly increased risk of migraines. Some studies indicate that the risk is also due to higher homocysteine levels[ref], while other studies show that it may be due to the methylation of certain genes.[ref]
Meta-analyses showed that the MTHFR C677T variant increased the risk of migraines with aura for all population ancestry groups. In non-Caucasians, the C677T variant increased migraine risk by 3-fold.[ref][ref] In North Indians, the A1298C variant was associated with the risk of migraines.[ref]
Related article: Getting to the root genetic cause of migraines
7. Detoxification and MTHFR
A methyl group is needed in the detoxification reaction for arsenic. The enzyme (arsenite methyltransferase) that metabolizes arsenic depends on the availability of methyl groups. The C677T variant is linked to decreased arsenic detoxification and increased skin lesions with exposure.[ref][ref]
Related article: Arsenic detoxification genes
Additionally, methylation is important in detoxifying mercury. In fact, MTHFR variants are tentatively linked to being more likely to have problems detoxifying mercury (small study).[ref][ref]
Related article: Mercury detoxification genes
8. Alzheimer’s and dementia risk for C677T
A 2026 meta-analysis pooled 26 studies across ethnicities to see how MTHFR variants affect Alzheimer’s and dementia risk. The results showed that the MTHFR C677T T allele increases the relative risk of both Alzheimer’s and dementia a little bit. There was no increased risk for carriers of the A1298C variant. This meta-analysis is useful because it is larger, across multiple studies, and across multiple ancestry groups.[ref]
Tradeoffs! Positive benefits of MTHFR SNPs
You may wonder why MTHFR variants – with such negative effects – are so common. It seems like a variant that should have been weeded out with natural selection. For common genetic variants, there is almost always a positive effect that balances the negatives. Plus, there are interactions between our modern world
The big positive for MTHFR C677T is that it protects against several common types of cancer. Folate is needed for cell growth, especially fast-dividing cancer cells, and the decrease in folate with MTHFR variants can protect against growth in fast-growing tumors.
Studies finding protective effects against cancer:
- A meta-analysis found that two copies of the C677T variant (AA genotype) decrease the risk of colon cancer by about 20%![ref]
- Another meta-analysis found that two copies of the C677T variant (AA genotype) were protective against prostate cancer.[ref]
- The MTHFR C677T variant decreases the relative risk of retinoblastoma and oral squamous cell cancer.[ref][ref]
- Two copies of the C677T variant (AA genotype) are protective against gastric cancer.[ref]
However, for someone who has cancer, the MTHFR C677T variant is associated with poorer outcomes.[ref]
The MTHFR A1298C variant (GG or GT) is associated with a decreased risk of hypothyroidism according to multiple studies, meta-analyses, and trial sequential analyses.[ref][ref]
The flip side: Folate can also help protect against cancerous mutations in the first place. A lack of folate is linked to double-strand DNA mutation replication. If those mutations occur in a gene important to cancer prevention, then a tumor can occur.[ref] Thus, folate helps to prevent the mutations that cause cancer, yet in someone who has cancer, folate and methyl groups can fuel cancer cell growth.
Table: Risks and Benefits: Overview of MTHFR Tradeoffs
| Variant | Increased Risks | Potential Benefits |
|---|---|---|
| C677T | Heart disease, stroke, neural tube defects, | ↓ Colon, prostate, gastric cancer |
| depression, migraines, pregnancy complications | ||
| A1298C | Migraines, depression (with two copies) | ↓ Hypothyroidism |
Gene expression and MTHFR:
MicroRNAs are short strands of RNA that can bind to an mRNA strand and block it from being translated into its protein. In cell studies, folate deficiency upregulates miR-22 and miR-149. These two miRNAs bind to the MTHFR mRNA and keep it from being turned into the MTHFR enzyme when folate is lacking. Interestingly, the effects of folate deficiency regulate miRNA differently in cancer cells vs. non-cancerous cells. Those same miRNAs also affect tumor suppressor genes.[ref]
While a lot more research is needed here, the impact of miRNA on both tumor suppressors and MTHFR may be part of why folate is both beneficial for preventing cancer and then detrimental during some types of cancer.
Lifehacks: Diet and Supplements for MTHFR
Knowing that you carry an MTHFR genetic variant can help guide your choice of foods and supplements. By optimizing your diet, you can easily mitigate the risks from the MTHFR variants.[ref]
Let’s explore some diet and supplement options for individuals with MTHFR variants.
Dietary considerations with MTHFR variants:
Increase folate-rich foods:
The RDA for folate is 400 mcg/day. Increasing your intake of folate (vitamin B9) from foods will help mitigate some of the risks from the MTHFR variant.
| Food | Micrograms (mcg) DFE per serving |
Percent DV* |
|---|---|---|
| Beef liver, braised, 3 ounces | 215 | 54 |
| Spinach, boiled, ½ cup | 131 | 33 |
| Black-eyed peas (cowpeas), boiled, ½ cup | 105 | 26 |
| Asparagus, boiled, 4 spears | 89 | 22 |
| Brussels sprouts, frozen, boiled, ½ cup | 78 | 20 |
| Lettuce, romaine, shredded, 1 cup | 64 | 16 |
| Avocado, raw, sliced, ½ cup | 59 | 15 |
| Spinach, raw, 1 cup | 58 | 15 |
| Broccoli, chopped, frozen, cooked, ½ cup | 52 | 13 |
| Mustard greens, chopped, frozen, boiled, ½ cup | 52 | 13 |
| Green peas, frozen, boiled, ½ cup | 47 | 12 |
| Kidney beans, canned, ½ cup | 46 | 12 |
Related article: Folate-rich foods and recipes for MTHFR
Is increasing dietary folate enough with MTHFR C677T?
Yes, according to several studies. For example, a recent study showed that simply increasing folate-rich foods reduced homocysteine levels and inflammatory markers in women with the MTHFR C677T variant.[ref] Another study showed that a ‘green’ Mediterranean diet, which was a Mediterranean-style diet supplemented with a daily Mankai green shake, improved folate levels significantly in people with MTHFR C677T typical and heterozygous (AG) genotypes.[ref] However, it does take consistently consuming folate-rich foods, though. So if you have the MTHFR C677T variant, be conscientious about your diet – or consider intermittent supplementation with low-dose methylfolate (e.g. up to 400 mcg) on days when you know you aren’t eating well.
Folate is also needed for other cellular reactions:
It’s important to note that MTHFR and the methylation cycle are only part of the picture with folate in the cell. In the mitochondria, folate is also used for supporting mitochondrial DNA maintenance and mitochondrial protein synthesis. This part of the folate cycle doesn’t involve MTHFR or methylfolate directly, which makes incorporating folate-rich foods in your diet important beyond just methylfolate.[ref]
Folic acid is not the same as natural folate:
Not everyone processes folic acid, the synthetic form of vitamin B9, the same way. People with DHFR genetic variants, especially in conjunction with MTHFR variants, may want to avoid the overconsumption of folic acid because it can build up as unmetabolized folic acid.
Does this mean that you should avoid all foods enriched with folic acid if you have MTHFR variants (and no DHFR variants)? In the context of a relatively healthy diet, consuming some folic acid – e.g. eating bread or a bun with fortified wheat – is likely not a problem for most people with MTHFR variants. A small amount of folic acid is metabolized even with MTHFR variants with no problems. The higher levels of unmetabolized folic acid correlate to supplements containing folic acid or to a high intake of processed foods with folic acid.[ref]
Related article – check DHFR genes: Folic acid and your DHFR gene
Get sufficient dietary choline intake:
Choline can help your body bypass a lack of folate in the methylation cycle.[ref][ref] Good sources of choline include egg yolks, beef liver, and wheat germ.
A type of choline called betaine (TMG) is what works through the methylation cycle. Food sources of betaine include beets, quinoa, and spinach, and are also helpful for optimizing the methylation cycle.
Related article: Choline-rich foods and recipe ideas
Your gut microbiome produces folate:
In addition to the folate we get from food, the bacteria in our intestines also produce folate. Some of the folate is then utilized by other gut bacteria, but some is absorbed into the body. Folate from food or supplements is mainly absorbed in the small intestine, and then folate from the gut microbiome is primarily found in the colon. A couple of studies involving colonic folate supplementation (done on colonoscopy patients) show that folate is absorbed in the colon. While it isn’t absorbed as quickly as it is in the small intestine, the longer exposure time allows for absorption.[ref][ref]
The question is: How much folate comes from the gut microbiome?
It depends on the composition of your gut microbiome, how much fiber you eat, your exposure to antibiotics, the effect of pesticides on your gut microbiome, how much folate you eat, and supplemental probiotics. Microbial folate is not enough to meet your daily need for folate, but it may provide part of what we use each day. Researchers use piglets as a model that is most similar to the human gut microbiome. A study showed in piglets that about 18% of their daily folate came from the gut microbiome.[ref]
In mice, a 2026 study showed that the mouse gut microbiome likely consumes more folate than it produces when eating a diet with plenty of folate (lab mouse chow contains lots of folate). However, when fed a folate-depleted diet, the mouse gut microbiome increases folate production. Interestingly, the researchers also showed that folate levels vary a lot between tissues, with the liver having the highest concentration and the stomach and intestines the lowest (100-fold difference).[ref]
The varying microbiome production of folate being dependent on dietary folate explains an earlier human study involving two hundred adults eating varied diets. The research found that the folate-producing bacteria in the gut microbiome varied widely between dietary patterns, but that overall plasma folate levels didn’t correlate with gut microbiome folate production.[ref]
Some Lactobacillus and Bifidobacteria species are folate producers, so the composition of the gut microbiome will affect folate production. One more complicating factor is that the type of folate produced by bacteria seems to be absorbed through the reduced folate receptor (RFC, SLC19A1 gene). This makes your folate receptor variants another possible interaction with intestinal folate production.[ref]
A 2026 preprint showed that, in mice, a high-dose probiotic containing L. plantarum, W. coagulans, and B. animalis subsp. lactis could increase plasma folate levels and decrease homocysteine.[ref] Human clinical trials on this are lacking, though, so I don’t know how a high-dose mouse probiotic correlates to humans.
Here’s something interesting: Supplemental folic acid and supplemental methylfolate affect the gut microbiome differently. A study using in vitro gut microbiomes (fecal slurry) showed that added folic acid promoted the growth of different bacteria than added methylfolate. While both types of folate increased Lactobacillus, Bifidobacterium, and Pediococcus, only the methylfolate increased the relative abundance of Firmicutes (by 4.49%).[ref] A 2025 study on gut microbiome composition in children with neurodiversity showed altered Firmicutes levels.[ref] The connection between methylfolate and folic acid feeding different bacteria may explain differing results in people with neurodiversity if part of the effect is in the gut microbiome.
My theory: The differences in microbial folate production may explain why some people are more likely to have negative effects related to MTHFR variants while others are resilient — a combination of lack of dietary folate as well as lack of gut microbial folate. The flip side is that someone with more microbial folate and a moderate dietary intake of folate may have no issues from MTHFR variants.
Supplements for MTHFR:
If your diet doesn’t provide enough of the nutrients needed in the methylation cycle, the following supplements have research backing their possible benefits for the folate cycle and methylation cycle.
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Digging deeper: MTHFR is more than just C677T and A1298C
While the C677T and A1298C are the most well-studied variants, there are several other genetic variants in the MTHFR gene that either increase or decrease the enzyme’s function.
Genotype report: Additional MTHFR variants
Additional variants to check that decrease MTHFR enzyme function:
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Related B Vitamins and Methylation
Frequently Asked Questions (FAQ) About MTHFR:
What is the MTHFR gene, and what does it do?
The MTHFR gene codes for an enzyme (methylenetetrahydrofolate reductase) that converts folate (vitamin B9) into its active form.
Why it matters: This process produces methyl groups used for:
- DNA methylation (gene regulation)
- Neurotransmitter synthesis (brain health)
- Detoxification (removing toxins)
- Heart health (managing homocysteine)
What are the most common MTHFR variants?
The two most common variants are C677T and A1298C. These are single nucleotide polymorphisms (SNPs), not rare mutations, and are found in about half the population.
How can I check if I have an MTHFR variant?
You don’t need expensive genetic testing. You can check your raw data from 23andMe or AncestryDNA for the C677T (rs1801133) and A1298C (rs1801131) SNPs.
What do the C677T and A1298C results mean for enzyme function?
C677T:
- G/G: typical function
- A/G: enzyme function decreased by ~40%
- A/A: enzyme function decreased by 70–80%
A1298C:
- T/T: typical function
- G/T: slightly decreased function
- G/G: enzyme function decreased by ~20%
Are there other MTHFR variants that matter?
Yes, variants like G1793A (rs2274976) can also significantly decrease enzyme function, while others, such as rs9651118 and rs13306560, are associated with positive health outcomes like lower blood pressure or reduced risk of certain diseases.
How do MTHFR variants affect my health?
Variants like C677T and A1298C can reduce enzyme efficiency, potentially leading to higher homocysteine levels and impacting processes like detoxification, neurotransmitter production, and cardiovascular health.
What can I do if I have an MTHFR variant?
Optimizing your diet is key. Increase intake of natural folate (leafy greens, lentils, liver, asparagus, broccoli), choline (egg yolks, beef liver, wheat germ), and betaine (beets, quinoa, spinach). These nutrients can help mitigate the risks associated with reduced enzyme function.
Is folate the same as folic acid?
No. Folate is the natural form found in foods, while folic acid is a synthetic form used in supplements and fortified foods. Not everyone with MTHFR variants processes folic acid efficiently, so focus on natural food sources of folate.
Can increasing dietary folate help with MTHFR?
Yes. Studies show that increasing folate-rich foods can lower homocysteine and inflammatory markers, especially in people with the C677T variant.
Do MTHFR variants affect both men and women?
Yes. For example, MTHFR variants in fathers can also affect fertility and miscarriage risk Dads and MTHFR.
Should I get MTHFR testing done?
Understanding your MTHFR variants can help you dial in your diet and prevent many age-related chronic conditions. However, a specific test just for MTHFR is likely not necessary. Fortunately, the MTHFR SNPs are readily available in your raw data if you’ve already done genetic testing, such as through 23andMe or AncestryDNA.
What should I eat if I have MTHFR C677T?
Optimizing your diet to include plenty of natural sources of folate helps to mitigate the negative effects of the MTHFR variants. Folate-rich foods include leafy greens, lentils, many green vegetables, and liver. Vitamin B12 is also important, along with other B vitamins. Vitamin B12 is only found in animal-based foods, so people eating a primarily vegan diet may need to consider supplementing with a B-complex. Talk with your healthcare provider if you have questions about this.
What does compound heterozygous mean?
When an article on MTHFR talks about ‘compound heterozygous’, it is referring to having one copy of the MTHFR C677T variant and one copy of the A1298C variant. This combination reduces the efficiency of the folate-related enzyme by about 50%, making it important to consume plenty of folate-rich foods in the diet.
Is MTHFR dangerous or a disease?
While the variants in MTHFR increase the relative risk of several chronic conditions, they do not cause a specific disease on their own. Instead, it’s a combination of diet and environment that interacts to increase susceptibility due to the MTHFR variants.
Recap of your genes:
| Gene | RS ID | Your Genotype | Notes for Your Genotype | Effect allele | Effect allele frequency |
|---|---|---|---|---|---|
| MTHFR | rs1801133 | — | typicalone copy of MTHFR C677T allele, enzyme function decreased by 40%two copies of MTHFR C677T, enzyme function decreased by 70 – 80% | A | 0.33 |
| MTHFR | rs1801131 | — | typicalone copy of MTHFR A1298C (heterozygous), slightly decreased enzyme function by ~10-20%two copies of MTHFR A1298C (homozygous), decreased enzyme by about 20-30% | G | 0.3 |
| MTHFR | rs2274976 | — | typicalsomewhat increased risk of schizophrenia, cognitive issues possible for seniors with this genotype in conjunction with low vitamin B12associated with cleft lip, neural tube defect, higher homocysteine, and folate deficiency, increased risk of schizophrenia in children, cognitive issues possible for seniors with this genotype in conjunction with low vitamin B12, risk of lower bone mineral density if B12 is also low | T | 0.04 |
| MTHFR | rs4846048 | — | typicalincreased relative risk of cervical cancer through miR-522 interactionincreased relative risk of cervical cancer through miR-522 interaction | G | 0.3 |
| MTHFR | rs9651118 | — | most common genotypedecreased risk of liver cancer, slower cognitive decline in the elderly, lower homocysteine, type 2 diabetes (compared to T/T)decreased risk of lung cancer, lower homocysteine, type 2 diabetes (compared to T/T) | C | 0.2 |
| MTHFR | rs13306560 | — | typicalavg 2.6 mmHg lower diastolic blood pressureavg 5.2 mmHg lower diastolic blood pressure, protective against Parkinson’s | T | 0.05 |
| MTHFR | rs17367504 | — | typicalprotective against hypertension, preeclampsiaprotective against hypertension, preeclampsia | G | 0.14 |
| MTHFR | rs4846049 | — | typicaltypicaldecreased risk of migraines, lower relative risk of cervical cancer | G | 0.61 |
Related Articles and Topics:
References:
Abhinand, P. A., Manikandan, M., Mahalakshmi, R., & Ragunath, P. K. (2017). Meta-analysis study to evaluate the association of MTHFR C677T polymorphism with risk of ischemic stroke. Bioinformation, 13(6), 214–219. https://doi.org/10.6026/97320630013214
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Debbie Moon is a biologist, engineer, author, and the founder of Genetic Lifehacks where she has helped thousands of members understand how to apply genetics to their diet, lifestyle, and health decisions. With more than 10 years of experience translating complex genetic research into practical health strategies, Debbie holds a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. She combines an engineering mindset with a biological systems approach to explain how genetic differences impact your optimal health.