Methylfolate vs. Folic Acid: Best and Worst Forms of B9

Methylfolate vs. folic acid—what’s the difference, and which one is better?

Both methylfolate and folic acid are forms of vitamin B9. However, folic acid is a synthetic form that’s significantly less effective than methylfolate, which is a naturally occurring form of folate.

Discover the difference between methylfolate and folic acid and learn why folic acid supplementation may not prevent vitamin B9 deficiency. 

Vitamin B9 basics

Vitamin B9, also known as folate, is a water-soluble vitamin that belongs to the B vitamin family.

Folate is an essential nutrient that must be obtained from foods or dietary supplements. Once absorbed, several enzymatic pathways convert folate to tetrahydrofolate, dihydrofolate, and methylfolate. 

Methylfolate is the most active form of vitamin B9 and plays a vital role in the methylation cycle. This biochemical process facilitates the donation of a methyl group to DNA, proteins, and lipids. 

Methylation is crucial for many physiological functions, including DNA synthesis and repair, gene expression, neurotransmitter production, and detoxification pathways. 

Folate also plays a critical role in regulating levels of homocysteine, an amino acid that can increase the risk of cardiovascular disease and neurological disorders.  

Deficiency causes 

Folate deficiency is common, and research published in The Journal of Nutrition found that almost 50 percent of women of childbearing age have low vitamin B9 levels or a deficiency.

Inadequate intake of folate-rich foods is the most common cause of low vitamin B9 status. Regular alcohol consumption and age-related gastrointestinal changes can also contribute to deficiency.

Because folate deficiency is widespread, public health officials introduced mandatory folic acid fortification of bread, rice, breakfast cereals, and certain processed foods. 

While these policies have lowered the prevalence of deficiency, many individuals have methylenetetrahydrofolate reductase (MTHFR) gene mutations. This blocks the production of the MTHFR enzyme needed to convert folic acid into active methylfolate. 

According to a study published in Brain Sciences, between 30 and 40 percent of the population have at least one MTHFR mutation. This leaves a large proportion of the population at risk of folate deficiency despite consuming fortified foods or taking folic acid-containing vitamin supplements.      

Deficiency symptoms

Because methylfolate plays a crucial role in regulating various cellular functions throughout the body, deficiency can manifest in a wide range of symptoms.

Here are common signs and symptoms of folate deficiency:

• Neurological issues

• Memory problems 

• Confusion

• Digestive problems

• Loss of appetite 

• Depression and anxiety 

• Behavioral changes

• Mouth ulcers 

• Hair loss

• Pale skin

• Lightheadedness 

• Arrhythmia 

Folate deficiency is particularly problematic for women of childbearing age due to its role in DNA synthesis and gene expression. 

Lack of adequate methylfolate at the time of conception and during pregnancy significantly increases the risk of fetal neural tube defects and can lead to congenital heart disease. 

Watch this video to learn more about the crucial differences between folate and folic acid. 

What is folic acid?

Folic acid is a synthetic form of folate produced in laboratories by chemically processing and combining p-aminobenzoic acid (PABA), pteridine, and glutamic acid.

It’s relatively inexpensive to produce folic acid, which explains why this synthetic vitamin is used to fortify foods and can often be found in low-quality over-the-counter and drugstore supplements. 

Folic acid is a common ingredient in prenatal vitamins to reduce the risk of birth defects. However, the effectiveness of this form of folate has been questioned, especially in individuals with MTHFR mutation. 

What is methylfolate? 

Methylfolate is the biologically active form of folate that is readily absorbed and doesn’t require enzymatic conversion to be activated. 

This naturally occurring form of vitamin B9 can be obtained from various food sources or taken as a methylfolate supplement. 

“In contrast to folic acid, the production of methylfolate is considerably more costly and time-intensive as it involves methylation,” explains Dr. Berg. “This process mimics the body’s conversion pathways of folate, creating a compound that can be directly used by cells and tissues.”

Which is better, methylfolate or folic acid?

Folic acid can maintain adequate folate levels in individuals without the MTHFR gene mutation. However, many individuals can’t convert folic acid into methylfolate, leading to deficiency despite taking folic acid supplements. 

In addition, taking folic acid without being able to metabolize and process it into its active form can lead to excessive accumulation, which has been associated with various health issues.  

A study published in The American Journal of Clinical Nutrition found that elevated blood concentrations of unmetabolized folic acid (UMFA) are associated with an increased risk of cancer and neurodegenerative diseases.

Interestingly, this study also suggested that “Approximately 40 percent of older adults in the United States have UMFA that persists after a fast.” 

This prevalence aligns with the percentage of individuals believed to have genetic variations of the MTHFR enzyme. 

Many individuals are unaware they're affected because MTHFR mutations aren’t regularly assessed as part of routine health screening. This makes methylfolate a significantly better option to promote optimal folate status and prevent deficiency for most people. 

This has been confirmed by research published in The Journal of Clinical Nutrition. The evidence suggests that methylfolate supplements were more effective in raising folate levels than folic acid supplementation, regardless of MTHFR mutation status.     

It’s essential that pregnant women and those planning to conceive take a prenatal vitamin containing methylfolate to reduce the risk of neural tube defects. 

Pregnancy causes an increased need for folate to facilitate the growth and development of the unborn child. Taking methylfolate can meet these heightened requirements more efficiently, which helps reduce the risk of congenital problems.

Methylfolate-rich foods  

Methylfolate can be obtained from various food sources and is predominantly found in leafy green vegetables, nuts, and certain animal products. 

Here are some of the best dietary sources of methylfolate:

• Spinach

• Kale

• Swiss chard

• Collard greens

• Brussels sprouts 

• Broccoli 

• Asparagus 

• Okra 

• Avocado

• Citrus fruits 

• Beef Liver 

• Eggs 

• Sunflower seeds

• Walnuts 

Folate is a heat-sensitive nutrient, meaning that boiling and roasting can reduce the methylfolate content of foods. Therefore, it’s recommended to consume plenty of lightly steamed or raw vegetables rich in folate to promote healthy vitamin B9 levels. 

Key takeaways

Methylfolate vs. folic acid—which one is better? 

Methylfolate is a naturally occurring active form of folate that is readily absorbed and highly effective. In contrast, folic acid is a synthetic form that requires conversion into methylfolate. 

Unfortunately, around 40 percent of the population lacks the enzyme needed to convert folic acid into its active form. This explains why methylfolate is the significantly better choice for maintaining optimal folate status and preventing deficiency.

FAQ

1. Which is better, methylfolate or folic acid?

Methylfolate is considered the better form of vitamin B9, as it doesn’t require enzymatic conversion into a bioactive form. This is especially beneficial for individuals with a genetic mutation affecting the enzyme needed to activate folate. 

In contrast, folic acid is a synthetically manufactured compound that requires conversion and isn’t as effective in promoting optimal folate levels as methylfolate.  

2. What are the benefits of taking methylfolate?

Methylfolate is a bioactive form of folate that can be directly utilized by the body and has been found to be highly effective in maintaining folate levels and preventing deficiency. 

Taking methylfolate supports crucial physiological processes, including DNA synthesis, cellular regeneration, and neurotransmitter production. This form of vitamin B9 also reduces the risk of neural tube defects in pregnant women.

3. What are the symptoms of a methylfolate deficiency?

Methylfolate deficiency can manifest in a wide range of signs and symptoms, including gastrointestinal issues, ulcers, behavioral changes, depression, poor cognitive functions, and hair loss. 

4. Do you need to take vitamin B12 with methylfolate? 

Yes, it’s recommended to take methylfolate in combination with vitamin B12. Vitamin B12 and folate metabolism are closely linked and work synergistically to regulate DNA synthesis and gene expression. 

In addition, high doses of folate can mask a vitamin B12 deficiency. Combining these essential vitamins helps promote optimal nutrient levels and lowers the risk of unidentified deficiencies. 

Sources

1. https://pubmed.ncbi.nlm.nih.gov/28404832/ 

2. https://pubmed.ncbi.nlm.nih.gov/32722170/ 

3. https://www.sciencedirect.com/science/article/pii/S0002916523019196

4. https://pubmed.ncbi.nlm.nih.gov/16825690/