Folate vs Folic Acid: Best Form to Take?

Folate and folic acid: these two terms are thrown around interchangeably, and while you might know that both refer to a "good for you" nutrient, perhaps you're curious about whether these two words refer to the same thing.

The answer to that question is both yes and no: yes, folate and folic acid are both forms of vitamin B9. But no, they're not exactly the same thing either. Let's unravel the complexities of folate vs. folic acid, and explore whether you should seek folate, folic acid…or both!

Vitamin B9: Forms and benefits

Folate naturally occurs in foods like asparagus, broccoli, banana, avocado, wheat germ, kidney beans, and green leafy vegetables such as spinach. Many processed foods, such as enriched grains and breakfast cereals, are fortified with folic acid.

Folic acid, the synthetic form of vitamin B9 (folate) is the type that is commonly found in these fortified foods. Now, many manufacturers have started using the bioactive form, L-methylfolate.

Folate 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.

This is why it's so critical to be aware of how much vitamin B9 you're getting on a regular basis—and also whether your body is properly absorbing it, since not everyone metabolizes this nutrient with ease.

Best form of folate to take

The best form of vitamin B9 (folate) to take, especially for individuals with an MTHFR gene mutation, is the metabolically active form called L-methylfolate (also known as 5-methyltetrahydrofolate or 5-MTHF).

When increasing your intake, one thing to note is that the bioavailability of folic acid is different from that of folate from foods—in fact, L-methylfolate is 1.7 times more bioavailable than food folate. Because of this, a dietary folate equivalent (DFE) was established to reflect the higher bioavailability of non-food folic acid and folate compared to food folates. The idea behind this is was to create a "common" folate intake value, since bioavailability differs between the forms.

• 1 mcg DFE = 1 mcg food folate
• 1 mcg DFE = 0.6 mcg folic acid from fortified foods or non-food sources consumed with foods
• 1 mcg DFE = 0.5 mcg folic acid from non-food sources taken on an empty stomach

Are non-food folic acid sources enough?

Getting folic acid from non-food sources 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 acid must 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 add to that 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. Note that according to the NIH, only about 50% of folate naturally present in food is bioavailable—making additional sources all the more critical.

What is impaired folic acid metabolism?

People with a genetic polymorphism in the methylenetetrahydrofolate reductase (MTHFR for short) gene have an impaired ability to convert folate to its active form, 5-MTHF. (This is also known as a "SNP"– single nucleotide polymorphism.) Individuals with MTHFR genetic mutation(s) have impaired folic acid metabolism, which means they cannot efficiently convert folic acid to its active form (L-methylfolate) because of their reduced activity of the enzyme required to convert it.

It is estimated that between 5-10 percent of the global population has a mutation that reduces MTHFR activity by 70 percent. In North America, Europe, and Australia, about 8-20 percent of the population has this mutation.

Health problems associated with MTHFR gene mutations

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, such as depression or anxiety
• Repeated miscarriages or infertility in men and women
• Pregnancies with neural tube defects

...and more.

How to test for MTHFR gene mutations

To find out if you have an MTHFR gene mutation, 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 (and impaired folic acid metabolism). 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.

References

• Bezold, G, et al. "Homozygous methylenetetrahydrofolate reductase C677T mutation and male infertility," The New England journal of medicine, April 2001, https://pubmed.ncbi.nlm.nih.gov/11302150/
• Bottini, F, et al. "Metabolic and genetic risk factors for migraine in children," Cephalalgia: an international journal of headache, June 2006, https://pubmed.ncbi.nlm.nih.gov/16686913/
• Moll, S, Varga, EA. "Homocysteine and MTHFR mutations," Circulation, 2015, https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.114.013311
• Ohrvik, Veronica E. et al. "Human Folate Bioavailability." Nutrients, April 2011, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3257685/
• Prinz-Langenohl, R, et al. "[6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C-->T polymorphism of methylenetetrahydrofolate reductase: 5-MTHF and FA supplementation and plasma folate," British journal of pharmacology, December 2009, https://pubmed.ncbi.nlm.nih.gov/19917061/
• Weisberg I, et al. "A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity," Mol Genet Metab., July 1998, https://www.ncbi.nlm.nih.gov/pubmed/9719624
• "Folate." Linus Pauling Institute. https://lpi.oregonstate.edu/mic/vitamins/folate
• "Folate," Nih.gov. https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/
• "MTHFR gene." MedlinePlus, https://medlineplus.gov/genetics/gene/mthfr/