card payments
Free Shipping Available On All Orders

What is 5-MTHF? The Ultimate Guide to Folate & Methylfolate

Written by Tom Von Deck
Reviewed by Kimberly Langdon
5mthf label intelligent labs supplement

What is 5-MTHF? This guide is intended to provide you with all of the most helpful and evidence-based information about vitamin B9, folate, folic acid, 5-MTHF, and the supplements and foods that keep your B9 at healthy levels.

You’ll learn about the problems that can lower B9 to unhealthy levels – even if you’re taking supplements or eating folate-rich foods – and how to solve or prevent them. Consider it an FAQ for current and prospective users of folate supplements or for those who are merely curious.

The nutrition of B vitamins is a very nuanced subject. There are many decades of scientific studies about their effects, how they positively and negatively interfere with foods and drugs, the best forms of B9 to take, and so much more. We went digging through these studies so that you don’t have to.

If you have any questions that are important to you that are not answered in this guide OR…

You need more clarity about one of our answers and/or you don’t understand it OR…

You disagree with anything in the guide…

Don’t be a stranger! Let us know! Contact us or leave a comment below.

What is Folate?

Eggs, beans, and bread are sources of folate

The word “folate” describes a family of nutrients found in foods, especially green leafy vegetables, beans, and eggs. These are naturally occurring and water-soluble forms of vitamin B9. (1)

Normally, people use the word “folate” as if it describes a single nutrient. “Folates” might just make you sound funny because this plural form is less common.

Foods high in folate include kale, broccoli, citrus fruits, asparagus, bananas, beans, and liver. (1)

Beans and liver provide far more natural folate than the other foods in the above list.

If a person has high folate needs or is deficient after consuming a lot of it, it is very likely that food is not the best way for them to get folate. There are diseases and genetic factors that can prevent people from metabolizing folate in foods. Keep reading for more details.

What is Folic Acid?

Folic acid is a synthetic and water-soluble form of vitamin B9. It’s normally created for supplementation. Many loaves of bread, pastries, and cereals contain folic acid.

spaghetti is fortified with folic acid in many countries

In 1998, the USA mandated that folic acid be added to particular grains to ensure adequate B9 intake on a mass scale.

As of 2017, 86 countries mandated through law that wheat flour must contain some minimum level of folic acid. (2)(3)

16 of the 86 did the same for maize flour. Six nations also added rice flour to the list.

What is 5-MTHF?

5-methyltetrahydrofolate, or 5-MTHF, is a natural form of vitamin B9 your body is ready to absorb and use for nutritional purposes. It is now a very popular form of folate for this reason, especially among people who have problems metabolizing other forms of B9 from foods and supplements.

5-MTHF Synonyms:

  • L-5-MTHF
  • L-methylfolate
  • L-methylfolate calcium (only if it’s bound to calcium salt)
  • Methylfolate
  • Levomefolic acid

Note the “L” in some of the above names. This letter indicates that the vast majority of human bodies can absorb it. “6(S)” instead of “L” indicates this as well.

If the “L” is replaced with “6(R),” then the formulation probably won’t help you much.

Which Form of Folate Does Your Body Best Absorb & Use?

A study published in the British Journal of Pharmacology compared the body’s absorption of 6(S)-5-MTHF to folic acid. Subjects were healthy women who had problems absorbing food-based folate and folic acid because the genes required to process these nutrients were faulty. 6(S)-5-MTHF was far better at getting usable vitamin B9 into the blood plasma where it can begin working its magic.

In this study, researchers used 6(S)-5-MTHF that was bound to calcium salt. Yes, it did run circles around folic acid in terms of absorption…


Another study compared the calcium-based stuff with another form of 6(S)-5-MTHF bound to glucosamine instead of calcium in rats. Researchers also compared both of them to folic acid. The study showed 1.8 times higher peak blood plasma levels than 5-MTHF bound to calcium salt and 3.1 times higher levels than folic acid. (5)

1mg 5mthf l-methylfolate as quatrefolic acid supplement

This is why Intelligent Labs uses the 6(S)-5-MTHF bound to shellfish-free glucosamine. In our supplements, we use a patented formula called Quatrefolic Acid® and we offer 1mg 5-MTHF and 5mg 5-MTHF.

5-MTHF Brand Names

Metafolin® – A 5-MTHF supplement using L-methylfolate calcium. It’s available only through sellers licensed by its creators.

Deplin® – Available by prescription, this 5-MTHF formulation was created to meet the nutritional needs of depressed patients and enhance the activity of antidepressant drugs.

Quatrefolic Acid® – Again, this is the stuff we use at Intelligent Labs. Patented internationally by Gnosis, it is the most scientifically advanced 5-MTHF formulation on the market. This 5-MTHF is better-absorbed by your body because it’s bound to shellfish-free glucosamine instead of calcium.

Intelligent Labs has two 5-MTHF supplements available with two different dosages.


What Health Benefits Do Folate & 5-MTHF Provide?

Required for Essential Body Functions

B9 is required for making: (6)(7)(8)

  • Energy from carbs
  • DNA & RNA
  • Red & white blood cells
  • Melatonin, a chemical that regulates sleep
  • Important neurotransmitters like norepinephrine, serotonin & dopamine
  • Your nervous system

bush beans are great sources of dietary folate

Prevent Birth Defects During Pregnancy

Healthcare providers often suggest that pregnant women supplement with folate while pregnant to prevent birth defects such as neural tube defects. This is because the effects of folate shortages on the baby’s development have been well-studied for a long time. (9)

Sufficient folate is required for the development of the nervous system during pregnancy. This is crucial from the beginning of the pregnancy. Women normally don’t realize they’re pregnant until a few weeks in. Even if you’re still trying to conceive, it’s a good idea to make sure your folate levels are up to par. (6)

ATTN Dads: This is for You, Too!

Men trying to conceive should also make sure they’re not folate deficient. A 2013 study found that men lacking healthy levels of this vitamin during conception may raise the probability of deformities considerably. (10)

Some women may be advised to start supplementing a few months before conception to increase the certainty of a healthy baby. (11)

Scientists have found 5-MTHF to be effective for depression symptoms

May Reduce Depression Risk and/or Enhance Antidepressant Drugs

Deplin®, a prescription form of 5-MTHF, was patented specifically for treating depression and enhancing the benefits of antidepressants in depressed patients. The way 5-MTHF helps with depression is unknown, but studies do show supplements can be helpful. Depression studies typically use very large doses compared to normal nutritional uses.

In a 2013 study of more than 500 patients receiving treatment for depression, automated phone surveys indicated a better average quality of life and increased satisfaction with their depression medications after three months. Satisfaction with relationships with relatives, friends, coworkers, lovers, and strangers also improved. The overall differences after 95 days were pretty dramatic. Subjects used a super-potent prescription form of 5-MTHF. Each dose was either 7.5mg or 15mg. A starting dose for normal 5-MTHF users without depression is typically 1mg or less. (12)

One reason for these benefits in depression patients could be that folate is an essential part of the production of major neurotransmitters like serotonin, dopamine, and norepinephrine and may help regulate them. (13)

5-MTHF may work well for some symptoms of bipolar disorder as well.

A six-week study of 10 people with major depression and bipolar disorder showed promising results: (14)

“The investigators found that patients with bipolar disorder taking L-methylfolate showed improvements in depression symptoms, functioning, cognition, and suicidal ideation.”

WARNING: If you suffer from depression, always talk to your doctor before using any form of folate supplement, even at low doses.

Reduce Homocysteine, an Inflammatory Chemical

Homocysteine is a compound in the human body that increases inflammation. Many diseases are rooted in inflammation.

High homocysteine levels may increase the risk of: (18)

  • Blood clots
  • Stroke
  • Alzheimer’s
  • Heart attacks
  • Coronary heart disease
  • Osteoporosis
  • Atherosclerosis

High levels of this compound are associated with low levels of vitamins B6, B9, and B12. This combination is a strong predictor of cognitive decline in men, and probably in women as well. (15)

Healthy levels of all three of these B vitamins are important for keeping homocysteine under control. 5-MTHF can prevent some cognitive decline on its own, but you’ll likely fare much better by keeping the other two at healthy levels as well. (15)(16)(17)

Other causes of high homocysteine levels include: hypothyroid problems, kidney diseases, and psoriasis. This means: don’t automatically blame vitamin B deficiencies. (18)

As you have already read above, laws in dozens of countries lowered homocysteine by mandating that flours be fortified with folic acid. A 24-week randomized placebo study demonstrated that 5-MTHF is a lot better than folic acid at lowering homocysteine levels in healthy humans. (19)