Leafy green spinach and other foods rich in folate and fortified folic acids

Best Form of Folate to Take? Folic Acid Awareness Week

Published: October 2021 | Updated: October 2021

The best form of folate to take is the metabolically active form called L-methylfolate (also known as 5-methyltetrahydrofolate or 5-MTHF).

However, folic acid, the synthetic form of vitamin B9 (folate) is commonly found in fortified foods and (historically) in vitamin supplements.

Spinach bowl

Folate naturally occurs in foods like green leafy vegetables such as spinach but many processed foods, such as enriched grains and breakfast cereals, are fortified with folic acid.

Folate has many benefits and is essential to many processes in the body including brain development and function, nucleic acid and amino acid metabolism, DNA synthesis and more. Its role in many methylation reactions also suggests folate is important for helping prevent certain cancers, cardiovascular disease and Alzheimer’s disease.

Is Taking Folic Acid Supplements Enough?

Cereals for breakfast

No, taking folic acid supplements and eating foods fortified with folic acid may not be enough to support optimal folate levels in populations with impaired folic acid metabolism. In the body, folic acidmust undergo several metabolic reactions in order to be converted to the active folate form. Although not currently a standard of care in mainstream medicine, the suggested alternative is to eat foods that naturally* contain folate and supplement with the metabolically active form of folate; L-methylfolate. L-methylfolate can increase plasma folate levels more effectively than folic acid, as it does not require any metabolic conversion or activation.

*Not all foods with naturally occurring folate are 100% bioavailable.

What is Impaired Folic Acid Metabolism?

People with MTHFR gene mutations (also known as SNP’s - single nucleotide polymorphisms) have often have impaired folic acid metabolism. Individuals with MTHFR genetic mutation(s) cannot efficiently convert folic acid to its active form (L-methylfolate) because of their reduced activity of the enzyme required to convert it. This enzyme is called methylenetetrahydrofolate reductase, or MTHFR for short.

It is estimated that between 5 -10 percent of the global population has a mutation (gene sequencing variant) that reduces MTHFR activity by 70 percent

How to Test for MTHFR Gene Mutations

Newborn baby with mother on the bed

To find out if you have an MTHFR gene mutation and impaired folic acid metabolism, you can take a simple blood or saliva (cheek swab) test.

Your genes (and gene mutations) are inherited from your parents. At conception, you receive one copy of the MTHFR gene from each parent for a total of two MTHFR genes. Mutations in either one or both can result in lowered enzyme activity. Non-mutated (normal) MTHFR genes are defined as C677C and A1298A. The lab test will tell you how many mutations, if any, you have. Depending on the mutation type(s), there are correlated varying degrees of enzyme activity ranging from 100% (complete activity) to less than 10 percent. In other words, those with a genetic mutation in MTHFR will have varying levels of difficulty creating the active form of folic acid, which is the important folate form the body needs to function properly.

Health Problems Associated with MTHFR Gene Mutations

Outcomes vary, depending on the person and their gene variant. Some conditions, signs, and symptoms associated with having an MTHFR gene mutation include:

  • Having high homocysteine levels (a risk factor for heart disease)
  • Abnormal vitamin B12 or B9 levels
  • Migraines
  • Nerve sensitivities
  • Mental health problems
  • Repeated miscarriages or pregnancies with neural tube defects and more.

Because folate is so essential during pregnancy, creating awareness for it is the primary objective of National Folic Acid Awareness Week. Due to the significant impact of MTHFR gene mutations on human health, including pregnancy, perhaps creating awareness for MTHFR should be part of this initiative.


  • https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/
  • https://lpi.oregonstate.edu/mic/vitamins/folate
  • https://www.lifeextension.com/magazine/2015/5/why-so-many-people-require-the-metabolically-active-form-of-folic-acid
  • https://www.ncbi.nlm.nih.gov/pubmed/19917061
  • https://www.ncbi.nlm.nih.gov/pubmed/9719624
  • https://www.lifeextension.com/magazine/2018/9/folate-improves-brain-function
  • https://www.ncbi.nlm.nih.gov/pubmed/11302150
  • https://www.ncbi.nlm.nih.gov/pubmed/16686913

By: Holli Ryan, RD, LD/N

Holli Ryan is a food & nutrition expert, registered & licensed dietitian-nutritionist, health & wellness writer, blogger, and social media specialist. She graduated from Florida International University and is a member of the Academy of Nutrition and Dietetics. In her free time she enjoys photography, travel, cooking, art, music, and nature.