Nutrient Spotlight: Folate

Any mom out there may recall that folate or folic acid (most common form of supplemental folate) was one of the first and foremost recommendations by their doctor right before or during pregnancy. The reason being – inadequate consumption of folate may lead to neural tube defects in infants, which are defects of the brain, spine, or spinal cord. They happen in the first month of pregnancy, most of the time even before a woman knows she is pregnant, therefore it is crucial to ensure adequate folate status if trying to conceive.

But you don’t have to be planning for pregnancy, and not even have to be a female to question your folate status as it is an important nutrient for health, immunity, and wellness.

What is Folate?

Folate is a water-soluble B-vitamin, also referred to as vitamin B9, and is naturally occurring in many foods as well as available in fortified foods and supplements. It acts as coenzyme in many important processes in the body, aids in healthy cell division, reduces inflammation, helps prevent vascular disease like atherosclerosis and aneurysm, promotes adequate functioning of the nervous, circulatory and cardiovascular systems, reduces the risk of birth defects.

The biological activity of folic acid and its derivatives affects the metabolism of important amino acids, such as methionine, homocysteine, serine, glycine, pyrimidine and purine synthesis and DNA methylation. The synthetic form of folic acid (most oxidized), which can be found in fortified foods and dietary supplements, does not show biological activity, meaning it is not readily absorbed. It is transformed in a series of reactions with the participation of many enzymes to form folates. The actively biological form is reduced folate (L-5-MTHF), which is transported together with the blood to cells where it undergoes biological processes important for our health. This information comes handy in picking the right folate supplement: to get the most readily absorbed version of folate, look for methylfolate  or L-methylfolate when considering supplementing.

Who is at Risk for Folate Deficiency

Some people, an estimated 53% to be exact, are at risk for not metabolizing folate adequately, putting them at risk for folate deficiency and as a result – increased homocysteine, a marker of inflammation predisposing for heart disease. The MTHFR gene, coding for the enzyme protein of the same name – methylene tetrahydrofolate reductase, is responsible for the catalysis of the enzymatic reaction, which is the reduction of the active form of folate. However, according to available literature, mutation of the MTHFR gene occurs in 53% of the population. People with MTHFR polymorphism need to be cognizant of their folate intake and homocysteine blood levels.

Although most people consume adequate amounts of folate, certain groups, including women of childbearing age and non-Hispanic black women, are at risk of insufficient folate intakes. Even when intakes of folic acid from dietary supplements are included, 19% of female adolescents aged 14 to 18 years and 17% of women aged 19 to 30 years do not meet the Estimated Average Requirement (EAR). Similarly, 23% of non-Hispanic black women have inadequate total intakes, compared with 13% of non-Hispanic white women.

Autism Spectrum Disorder

Emerging evidence suggests that periconceptional folic acid supplementation might reduce the risk of ASD or mitigate the potentially increased risk of ASD from prenatal exposure to certain drugs and toxic chemicals. The mechanism of these potential benefits is unknown, but it might be related to folic acid’s role in DNA methylation, which, in turn, can affect neurodevelopment.

Some, but not all, observational studies have shown associations between maternal use of folic acid and/or multivitamin supplements before and/or during pregnancy and lower risk of ASD in the women’s offspring.

Cancer

Several epidemiological studies have suggested an inverse association between low folate intakes and status and the risk of colorectal, lung, pancreatic, esophageal, stomach, cervical, ovarian, breast, bladder, and other cancers.

Cardiovascular disease and stroke

An elevated homocysteine level has been associated with an increased risk of cardiovascular disease. Folate and other B vitamins are involved in homocysteine metabolism, and researchers have hypothesized that these micronutrients reduce cardiovascular disease risk by lowering homocysteine levels.

Dementia, Cognitive Function, and Alzheimer’s Disease

Most observational studies conducted to date have shown positive associations between elevated homocysteine levels and the incidence of both Alzheimer’s disease and dementia. Elevated homocysteine levels might have a negative effect on the brain via numerous mechanisms, including cerebrovascular ischemia leading to neuronal cell death, activation of certain proteins leading to neurodegeneration. Some observational studies have also found correlations between low serum folate concentrations and both poor cognitive function and higher risk of dementia and Alzheimer’s disease.

Depression

Low folate status has been linked to depression and poor response to antidepressants in some studies. The possible mechanisms are unclear but might be related to folate’s role in methylation reactions in the brain, neurotransmitter synthesis, and homocysteine metabolism. However, secondary factors linked to depression, such as unhealthy eating patterns and alcohol use disorder, might also contribute to the observed association between low folate status and depression.

Recommended intake of Folate:

*Dietary Folate Equivalents (DFE)

Foods containing Folate:

*Daily Value (DV) based on 400mcg DV

With all the above health risks associated with unsatisfactory folate intake, it is important to ensure your diet is diverse and includes folate-containing foods. More so, if you are at risk for deficiency, planning a pregnancy or already pregnant, the importance of adequate intake is even higher.

Stay nourished my friends!

References:

1. National Institute of Health. Office of Dietary Supplements. https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/
2. Banyś K, Knopczyk M. The importance of folic acid for the health of the human body. DOAJ . 2020;76(2):79-87. doi:https://doi.org/10.32383/farmpol/118863