The Difference Between Folate and Folic Acid
Many medical professionals, nutrition experts and health practitioners claim that folate and folic acid are essentially the same nutrient, but there is a distinction between these two different compounds that is VERY important to know.
Folate
Folate is a general term for various tetrahydrofolate derivatives and is known as Vitamin B9. Over 150 different forms of folate have been identified that are naturally found in food, but the major type is called 5-MTHF (short for 5-methyltetrahydrofolate). When we grow and harvest fresh plants, they contain this natural form of folate. This natural form of folate provides a methyl group, which is one of the most important compounds in humans, functioning as an on switch and allowing important processes to occur.
Industrialization caused us to stop consuming fresh food and start consuming mass produced food products. The issue with mass production is food gets processed to extend its shelf life. This increases profits, but strips the food of many nutrients.
Stripping foods of their nutrients caused an increase in health problems and birth defects, but instead of fixing the problem by going back to whole and fresh foods, the chosen solution was to fortify processed foods with synthetic nutrients.
One of those nutrients is called folic acid.
Folic Acid
Folic acid is a synthetic compound that is not present in whole foods because it’s manmade. It’s used in dietary supplements and is only present in foods that are fortified with folic acid. Folic acid itself is lacking a methyl group and is inactive in the human body. In order for our bodies to put folic acid to use, it must first be converted into the active form, 5-MTHF.
Before being added to our food supply, folic acid was tested on rats, not humans.
Since rats have a high ability to convert folic acid into the active form of folate, we assumed that humans have a high ability as well, but not all people do.
Converting folic acid into methylated folate (containing a methyl group) requires multiple functional genes producing functional enzymes, which requires adequate cofactors. The enzymes produced must also be in an environment free of compounds that interfere with their function, such as medications, heavy metals, cytokines, chemicals.
Some people also have variations in genes that affect their ability to process folate, particularly folic acid. Estimates are that 40-60% of the population has at least one of these gene variations, which means that roughly half the population has an impaired ability to use synthetic folic acid. Those with these variations need metabolically active versions of folate since their bodies have trouble processing synthetic folic acid.
This is a problem if we’re relying on fortified foods or supplements that have high levels of folic acid, especially if the rest of our diet is low in natural folate.
Even without gene variations, we benefit from consuming active forms of folate versus synthetic folic acid.
If you’re told “only synthetic folic acid is proven to prevent neural tube defects” or “we don’t have enough data to recommend the biologically active form of folate”
here is what folate researchers have to say:
“Although there are no clinical trials on the effectiveness of 5-methylTHF in preventing NTDs [neural tube defects], metabolic studies have shown that 5-methylTHF is a biologically active form of the vitamin and it seems to be at least as effective as folic acid in improving folate biomarkers. The literature clearly shows that a better food folate intake is associated with better folate markers and that food folate can prevent NTDs (by increasing folate status). Folic acid can prevent NTDs by increasing serum or blood folate level. 5-MethyTHF can effectively increase serum or blood folate markers. Therefore, supplementing with 5-methylTHF for NTD prevention seems to be rational… [T]esting the efficacy of 5-methylTHF against a placebo would be unethical. Comparing the preventive effect of folic acid with a proposed better alternative (5-methylTHF) will require following several thousands of pregnancies over a long time. The costs of testing 5-methylTHF against folic acid would be extremely high. We do not have any reason to assume that a randomized controlled trial is justified before recommending 5-methylTHF.”
and:
“Folic acid itself is inactive in the human body, but is a precursor to the bioactive molecule 5-methyltetrahydrofolate (5-MTHF), which is formed in the liver by hepatic reductases. Folic acid is more heat stable than the active vitamin and costs much less, and is therefore the generally preferred form for production, sales and therapeutic use. However, this molecule is oxidized. It is naturally present in food in only trace amounts (Table 1) and molecular forms similar to folic acid are not found in nature. For these reasons, there has been much debate about the risk of side effects of folic acid supplementation and about the possible advantages of using its active form, 5-MTHF, which represents about 98% of all folate in plasma.“
and a review on folic acid vs. methylfolate in pregnancy concluded:
“Supplementation with 5-MTHF in pregnancy could be advantageous over that with folic acid, because 5-MTHF is immediately active, does not require metabolic activation, and is directly bioavailable to the mother and fetus and is not influenced by the possible MTHFR gene mutations.”
Originally, researchers thought folic acid was superior to food folate because it’s stable and very efficiently absorbed. However, absorption efficiency doesn’t matter if it’s not well utilized in the body.
Newer research has shown that folic acid can build up in the body. Researchers call it “unmetabolized folic acid” or UMFA:
“Dietary supplementation coupled with pervasive fortification of grain-derived foods with synthetic folic acid beginning in the late 1990s may have created a demographic with high serum levels of unmetabolized folic acid and high erythrocyte folic acid concentration. This is not theoretical, but has been demonstrated in a dose-dependent manner when levels of intake are over 200 mcg per day. Folic acid is detectable in fasting serum of a majority of subjects tested, and the proportions with detectable levels have risen since fortification programs were initiated.”
Why high levels of unmetabolized folic acid can be harmful:
It has no physiological benefit until it’s converted into active folate
Folate transport proteins bind it preferentially over more reduced active folate
Folate receptors bind it preferentially over more reduced active folate
It contributes to enzymatic inhibition of MTHFR
It reduces DHFR enzymatic function which reduces biopterin recycling, contributing to a biopterin deficiency (biopterins are cofactors for the synthesis of a number of neurotransmitters including dopamine, norepinephrine, epinephrine, and serotonin)
These negative effects of folic acid can lead to what is called a functional folate deficiency.
Unmetabolized folic acid has also been shown to accumulate in fetal blood supply in mothers who are supplemented with folic acid.
Researchers say:
“In light of our understanding of folate metabolism, there is growing concern about the risk to the fetus of high levels of inactive metabolites of folic acid, for both their oxidizing effects and a possible association with vitamin B12 deficiency. Instead, the administration of equimolar doses of 5-MTHF enables reaching the same target of maternal serum folate without generating inactive metabolites.”
Folic Acid Supplements
Many practitioners are not familiar with the biochemistry of folate and prescribe folic acid supplements to clients, often in high doses.
A common recommendation in reproductive endocrinology is to take 5,000 mcg of folic acid prior to an assisted reproductive treatment. I consistently saw women prescribed this when I spoke at fertility workshops. I warned them that folic acid can increase homocysteine, a marker of inflammation, and urged them to speak with their health care providers about methylated folate instead.
Synthetic folic acid is not only inefficiently metabolized, but it can actually have the opposite effect of what’s intended:
“It is now clear that the practice of prescribing high doses of synthetic folic acid should be at least a matter for debate. 5-MTHF, the “active” folate that is immediately available for conversion of homocysteine to methionine, should be proposed instead of folic acid for periconceptional support and even for nutritional supplementation in general.”
As one study explains:
“Folates often show strong substrate inhibition of the enzymes that make use of them, and modeling studies suggest that high folate levels could, under certain circumstances, have the same functional effect as low folate status.”
That means you could be causing a functional folate deficiency by taking high dose folic acid.
It’s also concerning that elevated homocysteine is an independent risk factor for miscarriage. High homocysteine is linked to injury in the vascular structures of the placenta that form early in pregnancy, potentially resulting in various obstetric complications such as recurrent pregnancy loss, fetal growth restriction, preeclampsia, placental abruption, and stillbirth.
Research has shown that prescribing high doses of folic acid to pregnant women results in maternal and cord blood levels of unmetabolized folic acid 5x greater than normal. Many studies have also documented high levels of unmetabolized folic acid in newborn infants, even in areas without mandatory food fortification programs.
The high dosage of folic acid supplementation often given in pregnancy is concerning because it doesn’t take very much to negatively affect folate metabolism in the body:
“Folic acid intake as little as 280 mcg saturates the capacity of dihydrofolate reductase, which is a critical step in folic acid metabolism and results in its appearance unaltered in the circulation.”
The phrase “unaltered in the circulation” is another way of saying that some of this folic acid does not get utilized by the body, meaning you have unmetabolized folic acid present in your blood.
In a 2015 research paper in the American Journal of Clinical Nutrition looking at unmetabolized folic acid in cord blood:
“…[B]ecause of concerns over potential adverse health outcomes, the functional ramifications of the observed high concentrations of folate and UMFA in maternal and fetal circulation in the current study warrant additional investigation. Specifically, the dose of folic acid in prenatal supplements should be reconsidered in light of our findings to provide the optimal health benefits to the growing fetus while avoiding undue risk.”
Without the presence of unmetabolized folic acid, natural folates may:
Bind to folate transport proteins freely
Bind to folate receptors freely
Help synthesize biopterin
Enhance cellular folate levels
Why is folate so important?
Besides preventing neural tube defects during pregnancy, it:
Helps prevent anemia
Helps conserve the amino acid glycine, which helps calm us down, get restful sleep, stabilize blood sugar, and maintain healthy skin and bones
Is important for methylation:
Methylation of the neurotransmitter dopamine makes your mind more flexible and less "sticky” or fixated.
Methylation of histamine reduces the severity of allergies and allergy-like symptoms.
Methylation is needed to make creatine, which supports bigger and stronger muscles, and reduces depression. It supports digestion, eyesight, skin health, and fertility as well.
Methylation clears homocysteine (methylfolate can reduce homocysteine instead of increase it)
Methylation boosts choline levels, which protects against fatty liver, supports the digestion of fats, helps muscle contraction, and supports sustained, focused attention.
Fortification
Folic acid is mandated to be included in processed foods by many countries around the world. Common places folic acid is found is in fortified food (called “fortified” or “enriched” foods and primarily comprise products made with white flour or other refined grains such as bread, rice, cereal, oatmeal, pasta and crackers), fortified nutritional yeast, energy drinks, nutritional drinks/shakes/bars with added folic acid, multivitamins, prenatal vitamins, B complex vitamins, and folic acid supplements.
Optimizing folate levels
Steps to optimize folate levels include:
Avoiding processed packaged foods containing synthetic folic acid (such as fortified grain products/refined carbohydrates)
Consuming whole foods containing natural folates (*Note: Folate is not stable in frozen vegetables, canned vegetables, or canned legumes, so fresh veggies (especially leafy greens) and sprouted legumes (sprouted have 4-6x more folate than raw) are the best plant sources of natural folate. Egg yolks and liver from pasture-raised animals are the best animal sources of natural folate)
Avoiding supplements containing folic acid
Utilizing vitamins or supplements containing L-Methylfolate (aka L-5-MTHF, 6S-5-MTHF)
Because most health practitioners and most employees at health food stores and supplement stores aren’t aware of the difference between folic acid and folate, I encourage you to do your own research, have conversations about it to spread the awareness, and read your food and supplement labels.
Now I’d love to hear from you. Have you tried incorporating more natural folate in your diet and reducing your exposure to synthetic folic acid? Were you shocked by how many fortified foods and supplements synthetic folic acid is in? Share and let me know!
P.s. If you know someone who might be struggling with functional folate deficiency, share this article with them!
P.s.s. If you’re interested in learning more about vitamins and minerals, you can check out my free workshop here.