Scientists are discovering that a gene called MTHFR and a vitamin called folate work together to control how your immune system behaves. When this system doesn’t work properly, it may contribute to autoimmune diseases like rheumatoid arthritis, lupus, and celiac disease. Think of it like a dimmer switch on a light—when the MTHFR gene and folate aren’t working well together, they can’t properly adjust your immune system’s activity level, which may cause it to attack your own body. This review brings together research showing how fixing folate levels and understanding MTHFR might help treat these diseases.

The Quick Take

  • What they studied: How a gene called MTHFR and a B vitamin called folate work together to control the chemical switches that turn immune system activity up and down in autoimmune diseases
  • Who participated: This is a review article that looked at existing research about rheumatoid arthritis, lupus, and celiac disease—not a new study with participants
  • Key finding: People with autoimmune diseases often have problems with their MTHFR gene and folate levels, which disrupts the chemical switches that normally keep the immune system balanced and prevents it from attacking the body
  • What it means for you: If you have an autoimmune disease, your doctor might want to check your folate levels and consider whether your MTHFR gene function could be affecting your condition. However, this is still emerging science, and you should talk to your doctor before making any changes based on this research.

The Research Details

This is a review article, which means scientists read and summarized all the existing research they could find on how the MTHFR gene and folate affect autoimmune diseases. They didn’t do a new experiment themselves, but instead looked at what other researchers have discovered about rheumatoid arthritis, lupus, and celiac disease.

The researchers focused on understanding the ‘one-carbon metabolism pathway,’ which is basically a series of chemical reactions in your body that need folate to work properly. These reactions create special chemical tags that sit on top of your genes and control whether they’re turned ‘on’ or ‘off.’ When the MTHFR gene doesn’t work well, these chemical tags don’t get placed correctly, which can cause immune system problems.

By reviewing all this research together, the scientists were able to see a pattern: in all three autoimmune diseases they studied, the same basic problem kept showing up—the MTHFR-folate system wasn’t working right, and this was connected to immune system dysfunction.

This approach is important because it helps doctors and researchers see the ‘big picture’ of how one broken system (MTHFR and folate metabolism) might be causing problems in multiple different autoimmune diseases. Instead of treating each disease separately, understanding this common root cause could lead to better treatments that work for several conditions at once.

This is a review article, which means it summarizes existing research rather than presenting new experimental data. The strength of this type of article depends on how carefully the authors selected and evaluated the studies they reviewed. The findings are based on research from multiple studies, which makes the conclusions stronger than any single study alone. However, because this is a review and not a new experiment, the conclusions are suggestive rather than definitive. More research is needed to confirm these connections and test whether treatments targeting MTHFR and folate actually help patients.

What the Results Show

In rheumatoid arthritis, researchers found that patients who haven’t started treatment yet show unusual patterns in their immune cells—specifically, their T cells (which are important immune fighters) have fewer chemical tags controlling their genes than normal. This happens because the MTHFR gene isn’t producing enough of a special molecule called SAM that’s needed to add these chemical tags. When folate levels are low or the MTHFR gene has variations that make it work poorly, this problem gets even worse.

In lupus (systemic lupus erythematosus), a similar pattern appears: immune cells called CD4+ T cells show the same lack of chemical tags, and their genes are stuck in an ‘on’ position that makes them produce too many inflammatory chemicals. This is connected to problems with MTHFR function and folate availability.

In celiac disease, the intestines show different patterns of chemical tags on genes, particularly in a type of DNA called LINE-1. This happens because eating gluten damages the intestinal lining, which prevents the body from absorbing folate properly. Without enough folate, the MTHFR system can’t work correctly.

Across all three diseases, the same basic problem appears: when MTHFR doesn’t work well and folate levels are low, the chemical switches that normally keep the immune system balanced get stuck in the wrong position, allowing the immune system to attack the body’s own tissues.

The research also suggests that the severity of autoimmune disease symptoms may be connected to how badly the MTHFR-folate system is broken. In other words, people with more severe problems in this system might have more serious autoimmune disease symptoms. Additionally, certain genetic variations in the MTHFR gene appear to be more common in people with autoimmune diseases, suggesting that inherited differences in this gene might increase disease risk.

This review builds on decades of research showing that folate is important for immune system function. Previous studies have shown that folate deficiency can cause immune problems, but this review brings together evidence that the MTHFR gene—which controls how your body uses folate—is a key factor in autoimmune diseases. This represents a shift from thinking about folate alone to understanding the whole MTHFR-folate system as a unit. The findings also connect to growing research on ’epigenetics,’ which is the study of how chemical tags on genes control their activity without changing the genes themselves.

This is a review article, not a new study, so it can’t prove that MTHFR and folate problems actually cause autoimmune diseases—it can only show that they’re connected. Most of the research reviewed was done in laboratory settings or with small groups of patients, so we don’t know yet if these findings apply to all people with these diseases. The review doesn’t include information about how common MTHFR problems are in the general population or how often they cause autoimmune disease. Additionally, while the research suggests that fixing MTHFR and folate problems might help treat autoimmune diseases, there’s limited evidence so far showing that treatments targeting these factors actually work in patients. More large-scale studies are needed to confirm these connections and test potential treatments.

The Bottom Line

Based on this research, people with autoimmune diseases might benefit from having their folate levels checked by their doctor (moderate confidence level). If folate levels are low, supplementation might be helpful, though more research is needed to confirm this (low to moderate confidence). Some people may have genetic variations in MTHFR that affect how they process folate, and genetic testing might help identify these individuals, though this is still an emerging area (low confidence). Anyone considering folate supplementation or genetic testing should discuss this with their healthcare provider first.

People with rheumatoid arthritis, lupus, or celiac disease should be aware of this research and might want to discuss MTHFR and folate status with their doctors. People with a family history of autoimmune diseases might also find this information relevant. However, this research is still in early stages, so it shouldn’t replace standard medical treatment. People without autoimmune diseases don’t need to worry about MTHFR testing based on this research alone.

If folate deficiency is found and corrected, some people might notice improvements in symptoms within weeks to months, though this varies greatly. The chemical changes in immune cells that this research describes would likely take weeks to months to shift. However, it’s important to understand that autoimmune diseases are complex, and improving folate status alone probably won’t cure these conditions. Benefits would likely be seen as part of a complete treatment plan with your doctor.

Want to Apply This Research?

  • Track daily folate intake (in micrograms) from food and supplements, aiming for the recommended daily amount of 400 micrograms for adults. Also track any changes in autoimmune disease symptoms like joint pain, fatigue, or digestive issues on a scale of 1-10.
  • Users with autoimmune diseases could use the app to log folate-rich foods (leafy greens, legumes, asparagus, broccoli) and set reminders to discuss folate and MTHFR testing with their doctor at their next appointment.
  • Over 2-3 months, track whether increasing folate intake correlates with any changes in symptom severity. Share this data with your healthcare provider to help inform treatment decisions. Also note any genetic testing results or doctor recommendations about MTHFR status.

This review article summarizes existing research and does not present new clinical trial data. The findings are suggestive of connections between MTHFR function, folate status, and autoimmune diseases, but do not prove cause-and-effect relationships. This information is for educational purposes only and should not replace professional medical advice. If you have an autoimmune disease or are considering folate supplementation or genetic testing for MTHFR, please consult with your healthcare provider before making any changes to your treatment plan. Do not stop or change any prescribed medications based on this information. Individual responses to folate supplementation vary, and what works for one person may not work for another.