Folic Acid Benefits: Community Awareness and Health Tips

Folic Acid Benefits: Community Awareness and Health Tips 

Nutrients are essential to human life. Folate, in particular, is a micronutrient required for optimal cell development and growth, as well as countless metabolic functions and processes. It’s involved in the synthesis of nervous system chemicals, blood vessel formation, hormones, and genetic materials. It works alongside proteins and other compounds to create active enzymes necessary for both mental and physical health. [1]

Folate is the natural form of vitamin B9. Folic acid is the synthetic form, which is most often used in supplements and fortified foods. 

We’ll be talking about why folic acid exists and how folate’s benefits compare to folic acid benefits, and why L-methylfolate is often superior to both. 

What is folic acid?

Folate is a water-soluble B vitamin that is naturally available in leafy green vegetables (such as spinach and lettuce), beans, peas, and liver. Numerous critical cellular pathways depend on folate as a one-carbon source, including DNA, RNA, and protein methylation, as well as DNA synthesis and maintenance. [2]

Folate was discovered in 1931 by Dr. Lucy Wills, a British medical researcher. She found that it was possible to reverse anemia during pregnancy by supplementing with brewer's yeast and spinach leaves. This turned out to be due to the folate content. Later on in the 1930s, folate was isolated from brewer's yeast. [3]

The synthetic form of folate, folic acid, was first created in 1946. Folic acid is not biologically active, so it has to be converted into dihydrofolate in the liver using an enzyme called dihydrofolate reductase (DHFR). DHF is then converted into tetrahydrofolate (THF), which is THEN converted into 5,10-methylenetetrahydrofolate and finally to 5-methylenetetrahydrofolate (or L-methylfolate for short - the active form of folate) by serine hydroxymethyltransferase. [4]

In the 1990s, international studies showed that taking folic acid for pregnancy reduced rates of neural tube defects (NTDs). This finding was believed to be among the many folic acid benefits for women, and led to many governments to recommend supplementation for all women of reproductive age. Flour was also fortified with folic acid in many countries to help restore folic acid deficiencies. It was later found that folic acid could ‘mask’ vitamin B12 deficiency - which could potentially cause neurological damage - so vitamin B12 was added to fortified flour as well. [5]

Benefits of folic acid

Unlike the natural folate present in foods, man-made folic acid is highly stable to oxidative degradation, which is why it is the preferred form used in foods. [6]This stability also means folic acid is more bioavailable than natural folate contained in food. [7] Natural folate lacks stability and is easily lost in cooking. 

Folic acid supplements are also relatively cheap to make, and are easier to source than the biologically active form, L-methylfolate. 

Methylfolate, on the other hand, is a newer form of folate that was approved by the FDA and released to market in 2001. It is already biologically active so there is no need for it to be converted any further in the body. It is immediately available for use upon ingestion. 

Folic acid deficiency symptoms

Deficiency of folate can lead to impaired cell division, accumulation of toxic metabolites, and impaired methylation (which is crucial for normal DNA/RNA function). 

Folate deficiency is most commonly associated with folate deficiency anemia. Signs include: 

• Ongoing fatigue and lethargy

• Muscle weakness

• Pallor (pale skin)

• Shortness of breath

• Mood issues, including depression and irritability

• Poor cognitive function

• Sore, red tongue (glossitis)

Things to be aware of when taking folic acid

Concerns have been raised that excess folic acid intake may have unknown consequences. [8]

While folic acid fortification is deemed safe and used in anything labeled as ‘enriched’ (including flour, grain, and cereal products), it’s important to understand whether it is right for you. 

As mentioned previously, folic acid is a synthetic and chemically stable form of folate and not the natural form of the vitamin found in whole foods.

One of the side effects of folic acid is that high dosages can build up in an unmetabolized form in the blood. This is because the conversion process is slow and depends on the availability of several enzymes. [9]

One study found a 19% increase in the risk of breast cancer in postmenopausal women taking ≥ 400 μg/day folic acid.  [10] The Swedish Mammography Cohort also found a statistically significant 19% increased risk of breast cancer in those taking multivitamins made with folic acid. [11]

High concentrations of UMFA (unmetabolized folic acid) in plasma have been found to decrease natural killer (NK) cell cytotoxicity, an immune response potentially promoting carcinogenesis. [12]

Studies in mice have also found that high folic acid consumption in those with an MTHFR mutation may cause degeneration of hepatocytes (liver cells) resulting in liver injury. [13]

In the elderly, a combination of high folate levels and low vitamin B-12 status may be associated with an increased risk of cognitive impairment and anemia and, in pregnant women, with an increased risk of insulin resistance and obesity in their children. [14]

Most importantly, some people have MTHFR genetic variations that decrease the body’s ability to convert folic acid. A mutated MTHFR enzyme may only have 55-70% of the efficiency of a normal MTHFR enzyme. The incidence of people presenting a form of polymorphism of MTHFR is about 40-50% worldwide. [15]

Levels of circulating UMFA in the population are persistent in countries where the folic acid fortification of grains and cereals has been implemented.

Who needs folate?

Folate plays an essential role in numerous bodily processes. It is vital for everyone, but certain individuals or life stages require it even more than others. 

Folate is required for:

• Pregnant women

Demands for folate increase during pregnancy because it plays a crucial role in DNA replication, amino acid synthesis and vitamin metabolism; all of which are required for growth and development of a healthy baby. Folic acid deficiency (which is actually folate deficiency) can lead to health issues in both the mother (anemia, peripheral neuropathy) and congenital abnormalities in the fetus. [17]

Studies show that unmetabolized folic acid (UMFA) has been found in the umbilical cord of the fetus, and even in infants' blood. [18]

• Those with cardiovascular concerns

Folate is required for converting homocysteine to methionine, which is critical for reducing homocysteine levels in the blood. Homocysteine is an amino acid linked to atherosclerosis, stroke, and blood vessel damage.

• Those with mood disorders and/or treatment-resistant depression

Folate is required for producing serotonin and dopamine, which are vital neurotransmitters involved in healthy mood and nervous system maintenance. Those with depression and other mood-related disorders are often found to be low in folate. [19]

Overall health and vitality

Folate is vital for detoxification, energy production, immune function, maintenance and regulation of genes, mood balancing, and control of inflammation. [20]

Why take folic acid? 

For most people, the main reason for taking folic acid is that their doctor has recommended it, and it is relatively cheap. Vitamin B9 benefits everyone, but methylfolate may be more beneficial for those who cannot absorb folic acid. 

Sources of folic acid

As folic acid is man-made, it is not present in any natural sources. Folic acid is added to certain products during the manufacturing process. Foods high in folic acid include breads, flours, pastas, rice, and cornmeal, corn masa flour (used to make corn tortillas and tamales); and some breakfast cereals. Folic acid is also found in certain dietary supplements. [21]

Benefits of methylfolate supplements

Those with a MTHFR mutation(s) are unable to properly break down folic acid, which will not only mean they are not getting the benefits, but may also be at increased risk of developing unmetabolized folic acid syndrome. [22]

For these people, it is much safer and more effective to take methylfolate, the active form of folate. Methyl-Life® has a carefully curated range of methylfolate supplements to suit every medical condition and stage of life. Methylfolate 2.5 mg is ideal for those who are pregnant and/or new to methylated supplements, while Methylfolate 5 mg is great for supporting cardiovascular health, healthy immune function, cognitive function, and many other methylation processes. 

Methylfolate 15 mg is ideal for those seeking optimal mood support. Clinical studies show that 15 mg methylfolate is effective for those with treatment-resistant depression when taken in combination with antidepressants. [23]

The takeaway

Folate is one of the most important nutrients for human growth, development, maintenance, and overall function. But it’s not to be confused with folic acid. Folic acid is the synthetic form of folate that has been used in fortified foods and supplements for the last 60 years. Folate itself is the form naturally present in foods, while L-methylfolate is the bioactive form available as a supplement that your body can immediately absorb and use.

Folic acid is safe but may not be suitable for everyone, particularly those who cannot metabolize it properly due to MTHFR genetic mutations. Talk to your health professional about what form of folate is right for you, and learn more about methylfolate at Methyl-Life®. 

References

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418216/

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257747/

3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235569/

4. https://www.ncbi.nlm.nih.gov/books/NBK554487/

5. https://www.sciencedirect.com/topics/earth-and-planetary-sciences/folic-acid

6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849489/

7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849489/

8. https://pubmed.ncbi.nlm.nih.gov/18326588/

9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849489/

10. https://pubmed.ncbi.nlm.nih.gov/16600944/

11. https://pubmed.ncbi.nlm.nih.gov/20335555/

12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508257/

13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340065/

14. https://pubmed.ncbi.nlm.nih.gov/18326588/

15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9380836/

16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218540

17. https://pubmed.ncbi.nlm.nih.gov/35204698/

18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026708/

19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1810582

20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9380836/

21. https://www.fda.gov/food/new-nutrition-facts-label/folate-and-folic-acid-nutrition-and-supplement-facts-labels

22. https://www.mdpi.com/2218-273X/12/2/197

23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402301/