Which is Better? Methylfolate vs Folic Acid

Image of folate-rich foods including eggs, legumes, broccoli herbs, fish eggs, oranges, and leafy greens with the wording methylfolate vs folic acid by The Healthy RD
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There are some important differences when you compare methylfolate vs folic acid.

As it turns out, their differences in your health can be dramatically different too. 

In this post, learn about the best form of folate to take and why folic acid holds some health risks for many. When it comes to folate supplements, methylfolate supplements are the best choice and we will review this as well. 

What is Folate?

Folate, or vitamin B9, has many names. Vitamin B9 can be called folate, methylfolate, folic acid, and other names.  

However, this may shock you: folic acid is not a vitamin at all. 

A vitamin is a “vital amine” meaning you can’t live without it.  Folic acid may become a vitamin (folate), but its fate is dependent on your genes and metabolism.

In the case of folate, the true vitamin B9, terminology, and forms really do matter.

In recent years, quality research is highlighting how synthetic nutrients are never as good as the natural forms of nutrients. The research with synthetic vitamin E was fraught with these issues in the 90s.

Now we are seeing issues with folic acid, the synthetic form of folate. There is no such thing as natural folic acid: it is made in a factory.

Somehow the correct terminology for folate has gotten lost, even in the world of research. So for clarification, the correct term for vitamin B9 is folate, not folic acid.

Related Post: 7 Nutritional MTHFR Supplements That Changed My Life

Methylfolate vs Folic Acid Overview

First, methylfolate is a natural form of folate, while folic acid is synthetic folate.  

Folic acid also requires conversion in your gut to become active.  Compare this to methylfolate, which is already active.  

Sadly, folic acid also isn’t absorbed as well as methylfolate.

Additionally, up to half the population has a variant in a gene called MTHFR.  This gene controls a lot of things, including whether or not folic acid works in the body. 

Although very close to methylfolate, folic acid has a key difference in its structure that requires this gene in your body to convert folic acid into an active form. 

If you have this gene, which most people do, folic acid doesn’t convert into active folate in the body very well.

Methylfolate vs Folic Acid: History

Folate was discovered in 1931 by Dr. Lucy Wills when she discovered that pregnant women became anemic without it.

This vitamin was first discovered in brewer’s yeast.

In 1943, Bob Stockstad successfully made artificial folate, also known as folic acid. This led to many foods being fortified with synthetic folic acid by 1998. 

Since then, research has found some issues with using folic acid as you will soon find out. 

On the opposite end of the spectrum, methylfolate is naturally occurring in foods like spinach, lettuce, collard greens, kale, broccoli, cauliflower, beef liver, and many others. You can also find methylfolate in supplements. Methylfolate is active so the body is able to readily use it. 

Are Folate and Folic Acid the Same?

No. Although very close to folate, folic acid has a key difference that requires a gene in your body to convert it to the active form.

Folic acid also requires a conversion in your gut to become active.  

As it turns out, up to half the population has a variant in this gene so folic acid gets “jammed up” in the body if you will. This gene variant is called an MTHFR enzyme polymorphism. Around 60-70% of people have an MTHFR gene polymorphism.  

This means that folic acid may be problematic for the majority of the population. 

In contrast, folate is the umbrella term for all forms of vitamin B9, with methylfolate being the biologically active form.  

Methylfolate vs Folic Acid in the Blood

Current research suggests that folic acid may not be used in the body correctly, and may leave unwanted and possibly damaging substances in the body.

Folic acid must also be converted by the liver into active folate, and this process doesn’t always go smoothly.

Natural folate from foods, however, is very efficiently used and absorbed in the gut, but folic acid is not.

Folic acid’s fate is also dependent on the health of the liver, which is not a certain fate..

However, other nutrients may help with the use of synthetic folic acid, such as other B-vitamins.

Not surprisingly, natural food sources of folate improve blood folate status by 60% more than an equal amount of folic acid in supplemental form.

Folate Functions

The function of folate in the body is a topic that at a glance is confusing, but it can be simplified.

One of the most important roles of folate in the body is its ability to turn homocysteine into methionine. To do this, folate donates methyl.

Because of folate, methionine then becomes S-adenosyl-methionine (SAMe), an important mood-stabilizing and anti-inflammatory compound in the body.

To get rid of excess homocysteine in the body, we need folate or we end up with increased rates of heart disease and inflammation. Your body also needs plenty of betaine to help reduce homocysteine in the body as well. 

Folate also helps the body make red blood cells. Vitamin B12 and iron are also needed for this purpose.  

Another important role of folate is that it helps prevent neural tube defects. This is why it is so important for women to get folate when they are pregnant. 

Symptoms of Folate Deficiency

The symptoms of deficiency of folate include:

  • Anemia
  • Fatigue
  • Mood changes
  • Depression
  • Digestive distress
  • Pale skin
  • Impaired immunity
  • Pregnancy complications
  • Difficulty with fertility

If you are low in folate, symptoms can be vague, so they often get missed. To prevent folate deficiency, you should make sure you eat plenty of folate-rich foods regularly. 

Folate-Rich Foods and Absorbability

Folate comes from the word “foliage” so as you might guess, green leafy vegetables are a good source of dietary folate. But there is more to the story because not all folate from foods absorbs well.

Whole foods that are rich in folate include:

  • Leafy green vegetables
  • Organic eggs: 143 micrograms 36% DV
  • Asparagus
  • Citrus fruits
  • Papaya
  • Broccoli
  • Beets
  • Brussels sprouts
  • Legumes
  • Potatoes cooked with the skin
  • Organ meats

Interesting research shows that folate from eggs has better absorption than plant sources of folate. Beef liver is also more stable and available for the body than plant sources of folate. 

Strikingly, green lettuce folate bioavailability is only 2.9% compared to over 70% bioavailable from eggs. And beans are only 4% absorbable. This means you may be best off eating folate from animal sources in addition to eating leafy greens. One way to make the folate you eat from spinach more absorbable is to chop it or blend it

How to Know if You Are Deficient In Folate

Many people don’t eat the healthy foods required to get adequate folate in their bodies. In addition, many drugs deplete folate, including:

  • Alcohol
  • Methotrexate
  • Diuretic pills
  • Laxatives
  • Mood stabilizers
  • Antidepressants
  • Anticonvulsants

If you are on these medications or your diet isn’t optimal, this means you could be low in folate. You should ask your healthcare provider about taking methylfolate supplements or a prenatal vitamin that contains methylfolate in these cases. 

How to Supplement Natural Folate

Names for natural folate in supplements are:

  • Methylfolate
  • L-Methylfolate calcium (refers to the calcium salt molecule it is attached to)
  • Metafolin and Deplin
  • 5-MTHF and L-5-MTHF (in this article 5-MTHF refers to L-5-MTHF)
  • Levomefolic acid
  • 5-methyltetrahydrofolate
  • (6S)-5-methyltetrahydrofolate and Quatrefolic

The active form of folate in the body is called levomefolic acid or 5-methyltetrahydrofolate (5-MTHF).

Natural folate works to lower homocysteine and correct nutrient deficiency equally or better than folic acid. This is because the body doesn’t need the MTHFR enzyme to make it active. 

Folic Acid Risks

New research is linking higher folic acid levels in the blood to overall increased cancer risk, including colorectal cancer. Folic acid also increases the risk of prostate cancer while dietary sources of folate are associated with a reduced risk of prostate cancer.

Additionally, folic acid may also increase the risk of all-cause cancer.

High folic acid intake can also mask a B12 deficiency while natural folate as methylfolate does not.

Watch out for your body’s signs. If you get nausea, irritability, or other symptoms, it could be a sign you aren’t metabolizing folic acid correctly.

Methylfolate vs Folic Acid: Pregnancy

Pregnant woman in a striped shirt with a bottle of vitamins for the methylfolate vs folic acid post by The Healthy RD

We are all familiar with the big emphasis on getting folic acid during pregnancy.  While good advice generally, there are issues. Let’s review how methylfolate vs folic acid works during pregnancy.

Folic acid does indeed reduce the risk of neural tube defects.

However, it is important to know that a large percentage of the population, even pregnant women, do not use folic acid correctly due to a mutation in a gene called the MTHFR gene. 

This does not mean that folic acid causes damage in all pregnancies with this gene, but it may affect some.

Notably, women with the MTHFR gene variant have higher rates of pregnancy losses.

For example, when women had multiple pregnancy losses and the MTHFR gene variant, methylfolate helped reduce miscarriages according to a small study.  This form of folate had positive effects on pregnancy outcomes in women who had this gene defect or gene variant.

Not long ago, folic acid supplementation was strongly recommended for all women, especially during their first trimester of pregnancy.

While this advice still seems to reduce the chances of neural tube defects, there are several reasons to consider adding natural folate or methylfolate instead.

Further, women who had the MTHFR gene variant and took folic acid during pregnancy were related to a reduction in lung function in their babies.

Methyfolate vs Folic Acid for Pregnancy: Verdict

Although it is too soon to generalize these findings to the public, what we do know is that the use of natural folate or methylfolate is safe and as effective as folic acid during pregnancy.

It may be prudent for women to check with their doctors about gene testing for MTHFR variants if there is a concern for miscarriage or other known risk factors for this gene.

One more thing: over half of babies born have folic acid in their cord blood that is not metabolized. This means that folic acid is not likely to help and may have potential harm to certain people.

Folate for Mood Disorders

Study 1
: In 2018, a study was conducted in people who had schizophrenia who were “stable” on antipsychotic medications.

Compared to a placebo, methylfolate at a dose of 15 mg per day increased plasma methylfolate levels and improved all symptoms of schizophrenia.

Just so you know, 15 mg of methylfolate is a LOT of folate but you can find supplements in that dose range.

Study 2: In yet another study, people with acute psychiatric disorders (DSM III diagnosis of major depression or schizophrenia) 1/3 of them had folate deficiency and they took part in a double-blind, placebo-controlled trial of methylfolate at 15 mg daily, for 6 months in addition to standard psychotropic treatment.

Among both depressed and schizophrenic patients methylfolate significantly improved clinical and social recovery.

The differences in outcome scores between methylfolate and placebo groups became greater with time. These findings add to the evidence implicating disturbances of methylation in the nervous system in the biology of some forms of mental illness.

Study 3: Yet another study of 100 patients with schizophrenia found that methylfolate combined with vitamin B12 had similar results with improvements to the previous 2 studies in schizophrenia symptoms.

It took 16 weeks to see improvement in symptoms of schizophrenia.

What were the side effects of methylfolate in all of these studies? None.

And folate does so much more.

Best Folate for Older Adults

In older adults, high folic acid blood levels are associated with worsening mental function, while natural folate as methylfolate is associated with improved mental function.

However about 1/3rd of older Americans have non-metabolized folic acid in their blood.

Methylfolate vs Folic Acid: Cost

Natural folate supplements cost more money than folic acid.  But you do get what you pay for.

However, folic acid isn’t likely bad for all people and is a better alternative than nothing when cost is a factor. Unless of course, you have had multiple pregnancy losses, or arguably, if you have cancer.

If you take any of the drugs mentioned above or don’t eat folate-rich foods, you need to carefully consider taking some form of folate at a minimum.

Foods Enriched with Folic Acid: Issues

Mandatory fortification of folic acid started in 1998; the government requires that cereal products be enriched with 140 micrograms of folic acid per 100 grams of cereal.

Neural tube defects have gone down but have not gone away, this is likely because of MTHFR genes, and of concern, may have contributed to increased miscarriage risk.

Vitamin B12 deficiency also increases risk of neural tube defects in babies, but this issue is rarely discussed. And folic acid masks vitamin B12 deficiency. 

To learn more about why folic acid can be harmful, visit Jeanette Kimszal, RD.

Can you get too much methylfolate?

In supplemental forms, yes. But you can’t get too much methylfolate from foods.

Some people react poorly to supplements, including methylfolate, in excess of their body’s needs. The results can be side effects like any other substances taken in excess.  For example, nervousness, anxiety, nausea, headaches, or skin rash can occur.

Side effects are much less likely to occur if taken with a balance of other vitamins and minerals.

Methylfolate is available both over-the-counter and with a prescription from your doctor.

Most importantly, folate is found in organic eggs, green, leafy vegetables, beef liver, etc, and eating a lot of these can help get more folate.

Blood Tests for Folate or Vitamin B9

In a nutshell, blood folic acid levels can falsely show adequacy of folate or even excessive blood levels of folate, despite not being able to function as folate in the body.

These folate lab tests aren’t accurate in the presence of MTHFR enzyme gene mutations, which means in at least 30-50% of the population.

However, it is always a good bet to take natural dietary supplements that contain moderate amounts of methylfolate to ensure that you get enough folate in your diet. 

Methylfolate vs Folic Acid Summary

It is best to avoid intake of synthetic folic acid and use natural methylfolate at this time.  This is based on the mounting research data suggesting that methylfolate is safer, more effective, and works for all people instead of folic acid which only helps some people. 

Always make sure to balance out natural folate with other B vitamins for its best metabolism. These days, you can find natural prenatal vitamins with methylfolate that are very reasonable in price. 

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body and is shared for educational purposes only. Consult your doctor or healthcare provider before making changes to your supplement regimen or lifestyle.


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