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What are the Symptoms of a Methylfolate Deficiency?

L-Methylfolate Deficiency Symptoms, Causes, and Treatment | Methyl-Life

What are the Symptoms of a Methylfolate Deficiency?

People who suffer from a methylfolate deficiency often have: 

● Fatigue

● Muscle weakness

● Tingling, burning, or numbness in extremities

● Shortness of breath

● Depression

● Memory problems

● Gastrointestinal issues, including abdominal pain

● Headaches

When your body does not get enough folate—also known as vitamin B9—in a form that it can assimilate, a host of problems can arise. B9 is an important vitamin involved in cell metabolism which plays acritical role in the synthesis of DNA, RNA, and proteins. There are several reasons why you may not be getting the folate you need, including that you are not converting the folate you intake into methylfolate, an active form of the vitamin.


Some people can get the folate they need from foods such as spinach and other dark green leafy vegetables, citrus juices, eggs, beans, nuts, meats, and grains, but a surprising percentage of people lack the ability to turn this folate into a form the body can absorb and process.

What is a Folate Deficiency?

With a true folate deficiency, you fail to take in enough folate from your diet. It is suggested that an average adult needs to take in at least 400 micrograms of folate or folic acid(the synthetic form of folate) to prevent deficiency. Pregnant and lactating women are recommended to intake 600 micrograms.


Not eating enough fresh fruits and vegetables or fortified grains? You just might be lacking enough folate for your needs.


Other causes of folate deficiency include diseases like celiac disease or Crohn's where you are unable to absorb nutrients properly and genetic conditions that prevent your body from converting folate into the bioavailable form, methylfolate, as well as side effects of some medications and excessive drinking of alcohol.

Is there a Difference Between a Folate and Methylfolate Deficiency?

In theory, there should not be a difference between a folate and methylfolate deficiency, as the body converts folate or its synthetic version, folic acid[1] ,into the methylated form. The reality, however, is that not everyone can properly convert the folate taken into the body.


Folate uses an enzyme called MTHFR to convert to L-5-methylfolate. Folic acid—folate's synthetic form—takes up to four conversions to become L-5-methylfolate.


A surprising percentage of people have a genetic mutation that prevents the body from properly creating 5-MTHF (active methylfolate) via MTHFR. This leads to deficiencies and symptoms even when the dietary intake of folate or supplementation through folic acid is sufficient. Thus, it is possible to have a methylfolate deficiency even when your body is taking in enough folate to meet your daily requirements.


Folate deficiency can sometimes mask a vitaminB12 deficiency because it covers up the effects of megaloblastic anemia which alack of B12 can cause. Supplementation with methylfolate does not cover up this type of anemia in the same way, so it can be easier to differentiate between the lack of B9 or B12.

Also Read: MTHFR Mutations and Vitamin B12 Deficiencies

Methylfolate Deficiency Signs and Symptoms

Methylfolate Deficiency Signs and Symptoms

When your body is not converting folate or folic acid into methylfolate, you may see a variety of symptoms. These include:

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● Being tired or fatigued, even after you have slept.

● Having headaches or feeling dizzy.

● Experiencing neurological issues like tingling or burning ("pins and needles"), especially in your hands and feet, or numbness.

● Struggling with depression, unusual poor judgment, or other cognitive and memory problems.

● Losing weight due to abdominal pain and gastrointestinal symptoms like nausea, vomiting, and diarrhea.

Many of these symptoms actually reflect megaloblastic anemia, which results from a B9(folate) or B12 deficiency. Your doctor or medical professional will often test for these deficiencies if you are diagnosed with anemia.


Other, less common symptoms of a methylfolate deficiency are:

● Tachycardia (excessive heartbeat) or tachypnoea (fast breathing)

● Trouble swallowing

● Mouth ulcers, fissures in the corners of your mouth, or sores on your tongue

● Heart murmur

● A condition called exfoliative dermatitis which causes the skin to redden and peel

● Petechiae (small, purple-brown spots under the skin caused by bleeding)

Additional neurological signs can be present that indicate a nutritional deficiency, especially in children.

Remember that you may be taking in an ordinarily sufficient amount of folate in your diet or through supplements, but your body is not converting that to the usable “methyl” form.

Who is at Risk for a Folate or Methylfolate Deficiency?

Who is at Risk for a Folate or Methylfolate Deficiency?

A wide variety of people can suffer from a folate or methylfolate deficiency. You may have increased risk if you fall into one or more of the categories listed below.

  • People Struggling with Alcoholism or Alcohol Use Disorders

Alcohol can speed up the breakdown and excretion of folate in your body, which means you aren't able to absorb what you need. This can happen even though you may seem to be getting enough folate in your diet or through supplementation.


Healthy men who drank even a moderate amount of alcohol consistently for a two-week period had lower serum concentrations of folate and B12 according to a2008 study.

  • Women of Childbearing Age

More than men, women in their early 20s tomid-40s are more likely to have deficiencies of these key B vitamins. Women with these vitamin deficiencies are at a higher risk of giving birth to a child with neural tube defects, or malformations in the brain and spine.


That's why it is crucial for women in this age group to make sure they are getting at least 400 micrograms of folate daily and, if possible, up to 1,000 micrograms.


If you are planning to become pregnant, and are experiencing any symptoms of folate or methylfolate deficiency, it's important to have your doctor test for problems (i.e. 5-MTHF blood serum levels, homocysteine levels, and more).

  • Pregnant Women

Because of the risk of birth defects, as well as the increased requirements for nutrition to support maternal health, women who are pregnant should be sure to supplement with folate. The American College of Obstetricians and Gynecologists recommends taking a daily prenatal supplement with at least 600 micrograms of folate.

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  • People with Malabsorptive Disorders

Celiac disease and other conditions that impact absorption of nutrients are more commonly diagnosed today, but even knowing that you have a malabsorptive disorder may not help you get the nutrients you need.


If you suffer from celiac, Crohn's, inflammatory bowel disease, or even something rare like tropical sprue, you could be lacking in folate. In fact, as many as 20%to 60% of patients with inflammatory bowel disease are deficient in folate.

  • People with the MTHFR Polymorphism

If your MTHFR gene has a specific mutation, you may not be producing the enzyme you need to convert dietary folate into methylfolate. This is most common in Hispanics, but many Asians and Caucasians also lack this enzyme.


In fact, as many as half of the world's population may have a MTHFR mutation. In order to get the amount of vitamin B9 required for good health, supplementation with 5-methyl-THF, the active form of folic acid, may be necessary.

Causes of Folate or Methylfolate Deficiency

If you have symptoms of folate deficiency or you have low serum levels of B9, there are some common causes to look into.


Your diet may be lacking. While many bread products and cereals in the U.S. are supplemented with folic acid, you may not be eating them -- or the fresh fruits, leafy green vegetables, nuts and seeds, and meats that contain folate.


You have a MTHFR genetic mutation. You can be tested to see if you have this genetic condition, which results in lower amounts of a crucial enzyme needed to convert dietary folate into a bioavailable form.


You suffer from a disease that impacts absorption. You maybe getting enough folate, but your body isn't taking it all in.


You are taking a medication that limits folate absorption. Drugs like phenytoin (Dilantin), trimethoprim-sulfamethoxazole, methotrexate, metformin, warfarin, sulfasalazine, and others can alter your body's ability to take in B vitamins, including folate.


You drink at least a moderate amount of alcohol on a regular basis. The occasional drink shouldn’t have much of an impact, but if you're drinking 8 ounces of wine or the equivalent each day, that could make it harder for your body to process folate.

Treating a Methylfolate Deficiency

Treating a Methylfolate Deficiency

Fortunately, in most cases, the treatment of a methylfolate deficiency is managed with regular supplementation.


For most, including those with a MTHFR mutation and those who have other issues with absorption, a methylfolate supplement is recommended. 


This is the bioavailable form of folate and will be more quickly and completely absorbed for direct use at the body’s cellular level. It may also be advantageous to look at your diet and include more fruits and vegetables, as well as limit alcohol consumption.

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