L-methylfolate is a type of folate that is biologically active and important for various biochemical processes in the human body. Unlike folic acid, L-methylfolate is easily used by the body and is a necessary nutrient for good health. 

In this article, we will discuss what L-methylfolate is, its benefits, and any possible risks associated with taking it. It is important to understand the importance of L-methylfolate and its potential advantages and disadvantages in order to make informed decisions about incorporating it into a health regimen.

What is L-methylfolate?

This medication is used to treat and prevent low levels of folate (vitamin B9) in individuals who have medical conditions, including depression. It is a type of folate that is vital for forming red blood cells and keeping the brain healthy. Folate is also crucial in promoting a healthy pregnancy and reducing the possibility of birth defects in the brain and spine. 

When someone consumes folate through their diet, their body is required to transform it into l-methylfolate before it can be utilized within cells. 

Nevertheless, if someone takes l-methylfolate in a supplement form, this conversion process becomes unnecessary. This means that l-methylfolate is more easily absorbed by the body than other forms of vitamin B9 like folic acid or folate.

L-methylfolate is essential for: 

  • DNA synthesis
  • Cellular function 
  • Methylation a process where a methyl group adds to DNA, proteins, or other molecules
  • Producing neurotransmitters such as dopamine, serotonin, and norepinephrine

It is important to keep in mind that the majority of individuals can acquire sufficient amounts of this essential compound through their daily meals. Leafy greens and legumes are natural sources of this nutrient, and they can also be found in some fortified foods like bread and cereals.

Benefits of L-methylfolate

There are a couple of benefits that l-methylfolate can contribute to our bodies. Here are some of its benefits: 

Helps with Depression 

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There is some evidence to suggest that L-methylfolate could potentially alleviate symptoms of depression for certain individuals. However, the research conducted on this topic has yielded mixed results.

A study conducted in 2012 involving 148 adults who were diagnosed with major depressive disorder examined the potential benefits of l-methylfolate in combination with selective serotonin reuptake inhibitor (SSRI) treatment. [1]

In the initial experiment, certain individuals were given 7,500 micrograms (mcg) of l-methylfolate per day for a duration of 30 days, then increased to 15,000 mcg per day for an additional 30 days. This was done in conjunction with taking SSRI medication. In contrast, a separate group only took SSRIs alongside a placebo.

According to the study, the participants who were receiving only SSRI treatment did not show any improvement when compared to the group taking l-methylfolate. However, during a second trial, when they increased the dosage of l-methylfolate to 15,000 mcg for the entire 60 days, the outcomes were different.

The researchers conducted a second trial with 75 adults, where they followed the same study design. These participants were given 15,000 mcg of l-methylfolate daily along with SSRI medications for 60 days. The results showed that l-methylfolate significantly improved depressive measures when compared to the SSRI plus placebo treatment.

Supports Brain Health 

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Studies indicate that individuals who have insufficient levels of folate are at a higher risk of cognitive impairment and dementia. Researchers hypothesize that this may be attributed to the correlation between low folate levels and chronic inflammation, which is a primary cause of various chronic illnesses, including Alzheimer’s disease. [2]

Studies have shown that increasing your folate intake can lower your chances of developing Alzheimer’s disease. One simple way to promote long-term brain health is by taking methylfolate. [3]

Promotes Heart Health

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Heart disease is the number one cause of death in the United States. However, studies indicate that consuming ample amounts of folate can decrease your likelihood of developing heart disease. But what exactly is the mechanism behind this effect?

Getting enough folate is important as it aids in the metabolism of the amino acid homocysteine. Elevated levels of homocysteine are linked to the development of blood clots and stroke. Studies indicate that getting adequate amounts of folate can decrease homocysteine levels, which can lower your risk of heart disease. [4]

Healthy Pregnancy

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When you’re pregnant, your body needs more folate than usual because it plays a crucial role in DNA replication and a variety of enzymatic reactions that are vital for the growth and development of your fetus.

Studies suggest that ensuring adequate folate intake can lower the likelihood of developing neural tube defects and other congenital abnormalities. It also reduces the risks of anemia, preterm birth, and pregnancy complications. That’s why many medical professionals recommend consuming a diet rich in folate and taking supplements such as methylfolate during pregnancy. [5]

Reduces Cancer Risk

Studies have indicated that folate can potentially help decrease the likelihood of certain types of cancer. The National Institutes of Health (NIH) has reported that individuals who consume sufficient amounts of folate may have a decreased risk of developing cancers such as bladder, breast, cervical, esophageal, lung, pancreatic, and stomach cancers. [6][7]

Side Effects of L-methylfolate

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The consumption of folic acid generally does not cause many adverse effects. However, if you experience any uncommon reactions after taking this supplement, it is important to inform your doctor or pharmacist without delay.

The side effects of L-methlyfolate include:

  • Difficulty concentrating
  • Overactivity
  • Confusion
  • Weight loss
  • Altered sleep patterns
  • Irritability
  • Excitement
  • Impaired judgment
  • Bitter or bad taste
  • Nausea
  • Abdominal distension 
  • Flatulence

It’s crucial to have a conversation with your physician regarding supplementation to ensure that your lab markers are within the normal range, as excessive consumption of L-methylfolate could potentially hide vitamin B12 deficiencies.

Is L-methlyfolate Better than Folic Acid? 

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L-methylfolate is a form of folate that is more easily absorbed by the body compared to folic acid, which is a synthetic version of folate commonly found in fortified foods and supplements. 

It’s worth noting that while L-methylfolate may be more bioavailable, it doesn’t necessarily mean that it’s better than folic acid. For most people, converting folic acid into L-methylfolate is not an issue.


L-methylfolate is an easily absorbed version of vitamin B9, also known as folate. It has been suggested that it could potentially aid in reducing depression symptoms for some individuals, but further research is required to confirm its efficacy. It’s important to note that taking l-methylfolate may lead to side effects like digestive issues and anxiety. Consulting with a medical professional is essential to weigh the potential advantages and risks before considering it.


These medications are utilized to cure or hinder low folate levels that can cause specific types of anemia. Inadequate diet, pregnancy, alcoholism, liver disease, specific stomach/intestinal issues, kidney dialysis, and other conditions may lead to low folate levels.
L-methylfolate is not usually prescribed for everyday use but rather as a supplement to other medications, as recommended by your doctor. It is also found naturally in certain foods, so it is best to get it from these sources whenever possible. 

It is important to make sure your vitamin B levels, especially vitamin B12 (cobalamin), are sufficient before adding L-methylfolate to your regimen.
L-methylfolate is a type of medical food that is specifically designed for individuals who suffer from folate deficiency-related conditions. In addition to this, it is also recommended for people who suffer from major depressive disorder and schizophrenia, especially those who have hyperhomocysteinemia due to folate deficiency.

Disclaimer: This article is only a guide. It does not substitute the advice given by your healthcare professional. Before making any health-related decision, consult your healthcare professional.

Editorial References And Fact-Checking

  1. Papakostas, G. I., et al. (2012). L-methylfolate as adjunctive therapy for SSRI-resistant major depression: Results of two randomized, double-blind, parallel-sequential trials.
  2. Corrada, M. M., Kawas, C. H., Hallfrisch, J., Muller, D., & Brookmeyer, R. (2005). Reduced risk of Alzheimer’s disease with high folate intake: The Baltimore Longitudinal Study of Aging. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association, 1(1), 11. https://doi.org/10.1016/j.jalz.2005.06.001
  3. Moretti, R., Torre, P., Antonello, R. M., Cattaruzza, T., Cazzato, G., & Bava, A. (2004). Vitamin B12 and folate depletion in cognition: a review. Neurology India, 52(3), 310–318.
  4. Zappacosta, B., Mastroiacovo, P., Persichilli, S., Pounis, G., Ruggeri, S., Minucci, A., Carnovale, E., Andria, G., Ricci, R., Scala, I., Genovese, O., Turrini, A., Mistura, L., Giardina, B., & Iacoviello, L. (2013). Homocysteine lowering by folate-rich diet or pharmacological supplementations in subjects with moderate hyperhomocysteinemia. Nutrients, 5(5), 1531–1543. https://doi.org/10.3390/nu5051531
  5. Greenberg, J. A., Bell, S. J., & Guan, Y. (2010). Folic Acid Supplementation and Pregnancy: More Than Just Neural Tube Defect Prevention. Reviews in Obstetrics and Gynecology, 4(2), 52-59. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218540/
  6. Kim Y. I. (1999). Folate and cancer prevention: a new medical application of folate beyond hyperhomocysteinemia and neural tube defects. Nutrition reviews, 57(10), 314–321. https://doi.org/10.1111/j.1753-4887.1999.tb06905.x
  7. https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/


  • Kim Monasterial, BSN

    Kim is a Registered Nurse and has been a medical freelance writer for more than six years. Starting off as a writer, Kim moved to proofreading and editing all the articles posted on HealthPlugged. She’s an enthusiast for health and wellness, being one to keep herself fit and adventurous for outdoor activities. LinkedIn


Kim is a Registered Nurse and has been a medical freelance writer for more than six years. Starting off as a writer, Kim moved to proofreading and editing all the articles posted on HealthPlugged. She’s an enthusiast for health and wellness, being one to keep herself fit and adventurous for outdoor activities. LinkedIn