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Medications to Avoid if You Have an MTHFR Mutation

Medications to Avoid if You Have an MTHFR Mutation

Discovering that you have an MTHFR mutation may answer some questions about your health and raise many more. You may be wondering how to manage your mutation and live a normal, healthy life.

With the right diet and supplements, it's entirely possible to optimize methylation in your body and reduce the risk of MTHFR-related health issues.

At the same time, you should be aware that certain medications may negatively impact an MTHFR mutation. Avoiding these medications or speaking with a healthcare practitioner about their results can help to minimize any harmful effects on your health.

This article will discuss the types of medications, drugs, and non-drugs that interact negatively with MTHFR mutations and why they should be avoided. We'll also explain what supplements are recommended for those with MTHFR in order to reduce the risk of nutritional deficiencies related to MTHFR mutations.

Types of Medicines That Negatively Impact an MTHFR Mutation

Types of Medicines That Negatively Impact an MTHFR Mutation

Anyone with an MTHFR mutation should, first and foremost, avoid taking any drug that could potentially deplete or block the utilization of folate in the body. The MTHFR polymorphism impairs the body's ability to convert folic acid into its bioavailable form, which can then result in low folate levels. This, in turn, affects a number of downstream methylation processes and can increase the risk of many health issues.

Common medications that affect folate stores in the body include:

  • Estrogen (birth control or menopausal medication)
  • Sulfa-containing drugs (Sulfamethoxazole, Sulfasalazine, Trimethoprim, Triamterene)
  • Methotrexate (amethopterin)
  • Metformin
  • Anticonvulsant drugs

Estrogen (Birth Control or Menopausal Medication)

The birth control pill is used to reduce the risk of unwanted pregnancies, whilst hormone replacement therapy (HRT) can help to minimize unpleasant symptoms associated with perimenopause. However, both birth control and hormone replacement therapy can deplete levels of B vitamins, including folate.[1]

Estrogen lowers the levels of vitamins required for remethylation (folate and vitamin B12) and transsulfuration (vitamin B6) of homocysteine. 

Research from a nutrition group suggests that blood folic acid levels can decline by up to 40% [2] in patients taking birth control, while a US study reported that taking birth control for five years can result in a 40% reduction of vitamin B12. The folate-dependent remethylation process is catalyzed by methionine synthase (MTR) and requires both 5-methylTHF and vitamin B12. [3]

Folate is also found to be significantly decreased in patients taking hormone replacement therapy. [4] This effect can increase homocysteine concentrations.

Sulfa-Containing Drugs (Sulfamethoxazole, Sulfasalazine, Trimethoprim, Triamterene)

These inhibit the enzyme Dihydrofolate reductase (DHFR), which catalyzes the reduction of dihydrofolate to tetrahydrofolate (THF). [5] This is the first of four different conversions the body must make in order to turn folate into methylfolate (the folate form your body can directly use). THF is required for the proper function of folate-dependent enzymes, which makes it essential for DNA synthesis and methylation.


Methotrexate is commonly prescribed for rheumatoid arthritis and many other immune diseases. It inhibits dihydrofolate reductase[6], an enzyme involved in regenerating tetrahydrofolate. Methotrexate also affects several other steps in folate metabolism, which can deplete folate levels and possibly further inhibit the MTHFR enzyme.

Other negative side effects of taking methotrexate alongside methylfolate include possible aggravation of psoriasis.[7]


Metformin is the main treatment for diabetes. It is known to cause vitamin B12 deficiency by its absorption in the gastrointestinal tract. B12 levels decrease significantly the longer metformin is taken, with one study finding that 16 weeks of metformin reduced levels of both folate and vitamin B12[8], causing an increase in homocysteine.

In such cases, methylfolate is the fastest and most effective[9] means of restoring depleted folate levels. No interactions have been found between L-Methylfolate Calcium and metformin.

Anticonvulsant Drugs

Anticonvulsants and antiepileptic drugs are shown to significantly reduce both serum folate and vitamin B12 [10] levels due to their induction of liver enzymes. This effect can lead to secondary cerebrovascular events in various epileptic patients.

Other Things to Avoid if You Have an MTHFR Mutation
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Other Things to Avoid if You Have an MTHFR Mutation

Several substances are known to deplete methyl groups, further impeding methylation. These should be avoided by people who have an MTHFR mutation.  

These include:

Excess Vitamin B3

Excess nicotinamide may deplete methyl groups and increase homocysteine levels. Hypertensives (such as thiazide diuretics, angiotensin converting enzyme inhibitors (angiotensin-converting enzyme), calcium channel blockers and beta blockers may also affect methylation by increasing fasting plasma levels of unmethylated substrates, nicotinamide, homocysteine, and norepinephrine.

Heavy Metals

MTHFR is involved in metabolizing heavy metals such as copper, mercury, and arsenic from the body. Exposure to these metals is shown to increase homocysteine levels in the presence of low vitamin B12 and folate concentrations.


Alcohol and acetaldehyde have an adverse effect on folate metabolism. High alcohol intake and low folate status due to the MTHFR 677TT genotype suggest that alcohol inhibits one-carbon metabolism, causing markedly elevated serum levels of homocysteine and DNA hypomethylation.


Folate plays a major role in the production of neurotransmitters. Chronic stress can exacerbate symptoms of depression and anxiety in those with an MTHFR mutation. Although stress is not always avoidable, it’s important to focus on minimizing stress as much as possible through things like meditation, yoga, diet, and other mindfulness exercises.

What is the Best Supplement to Take if You Have MTHFR

What is the Best Supplement to Take if You Have MTHFR?

Those with an MTHFR mutation are typically low in folate, as well as B12 and B6. Correcting these deficiencies is best achieved via supplementation with methylated nutrients. 

Folate is absolutely essential for almost every aspect of daily function. It's particularly important for long-term cardiovascular and emotional health. Without it, the methylation process is impaired, which has serious consequences for other bodily processes.  

Common mutations in the MTHFR gene can reduce the production of folate by up to 70%. Supplementing with methylfolate is the most effective way to bypass this mutation as it does not require conversion mediated by MTHFR and is more easily absorbed and utilized than folic acid. 

This can help to improve folate levels, which can, in turn, minimize the risk of developing health conditions related to low folate. Things such as elevated homocysteine, depression, and dementia. 

Choosing the right methylfolate supplement is crucial. Some of the most highly recommended methylfolate supplements are in the Methyl-Life® product range:  Methylfolate 7.5+, Methylfolate 10, and Methylfolate 15.

Each product in the Methyl-Life® range contains the internationally-patented Magnafolate® PRO  [(6S)-5-methyltetrahydrofolic acid, Calcium salt, Type C Crystalline molecule (L-Methylfolate)]. 

These products are formulated especially for people with a heightened need for bioavailable folate due to an MTHFR mutation.

This unique and internationally-patented L-5-Methylfolate is three times more pure and stable than other L-Methylfolates available on the health supplement market today. 



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