Folate, folic acid, folinic acid, methylfolate and l-methylfolate are all names used to categorize folate.
Folate is typically used as an umbrella term as a reference to the different forms of folate, similarly to how vitamin E encompasses the 8 different specific forms of vitamin E. However, folinic acid is not a form of folate and is actually a cancer drug, though it's commonly mistaken for folic acid.
Similar to some other vitamins, the different forms of folate exert different functions and have separate implications. Discover the most important facts about folate and never fret again!
Folate Versus Folic Acid
Labeled vitamin B9, folate is an essential water-soluble B vitamin that has numerous forms. It serves several important roles in the body and deficiency is associated with numerous health complications.
So, is folate the same as folic acid? No.
Folate is the naturally occurring form of folate found in food. Folic acid, however, is a synthetic form used in supplements and fortification of foods.
Before folate is fully absorbed, it is converted into another popular folate reference known generically as methyl folate and scientifically as levomefolic acid (5-MTHF). Indeed, folate is closely related to well-known MTHFR gene mutation.
On the other hand, not all folic acid, otherwise called pteroylmonoglutamic acid, is absorbed well.
Before intestinal absorption, folic acid needs to be converted into folate in the liver and/or other tissues and then into the active 5-MTHF form. This process is slow and inefficient, making whole food sources of folate and supplements that include the 5-MTHF form most supreme.
Food Sources of Folate
Perhaps of interest, folate is derived from the Latin word 'folium' which means leaf. Fitting, because leafy greens are among the highest sources of absorbable folate! High folate foods include:
• Dark leafy greens - turnip greens, spinach, romaine, kale, mustard greens
• Brussel sprouts
• Beans and legumes
• Sunflower seeds
• Whole grains, especially white rice
• Fortified breads and cereals
The recommended dietary allowances for folate are expressed as micrograms (mcg) of dietary folate equivalents (DFEs). They were developed this way to account for the different absorption rates of different forms of folate.
65 mcg DFE
65 mcg DFE
80 mcg DFE
80 mcg DFE
150 mcg DFE
150 mcg DFE
200 mcg DFE
200 mcg DFE
300 mcg DFE
300 mcg DFE
400 mcg DFE
400 mcg DFE
600 mcg DFE
500 mcg DFE
400 mcg DFE
400 mcg DFE
600 mcg DFE
500 mcg DFE
Folate Deficiency and Toxicity
Thanks to the fortification of breads, cereals and some other food products, folate deficiency is rare. In addition, overt toxicity is rare, except when ingested in the form of folic acid.
Overt folate deficiency is sometimes called megaloblastic anemia but is quite uncommon. If present, it is usually related to additional nutrient deficiencies.
However, certain groups of people are more at risk for folate deficiency including:
• Those with alcohol use disorder
• Women of childbearing age
• Pregnant women
• Those with malabsorption issues like celiac disease, short bowel syndrome, and gastric bypass surgery
• Anyone with an MTHFR gene mutation.
Symptoms of folate deficiency:
• Sore tongue
• Ulcerations on the tongue and throughout the oral cavity
• Changes in skin, hair or fingernail pigmentation
• GI Conditions
• Weakness and fatigue
• Shortness of breath and irregular heartbeats
• Elevated homocysteine levels
Folate deficiency is also associated with a higher risk of giving birth to infants with neural tube defects and low birth weights and preterm deliveries, which will be further discussed below.
High intakes of folate derived from whole food sources are not associated with toxicity concerns. However, the upper limit of 1000 mcg was established for folic acid because excessive intake of this form is linked to health risks.
It is first important to understand that a folate and/or B12 deficiency can lead to megaloblastic anemia. Depending on which nutrient is causing the deficiency, symptoms could look and feel differently.
Although it seems like a paradox, too little folate from food can lead to megaloblastic anemia but too much folic acid is associated with masking B12 deficiencies that can lead to irreversible neurological damage. So, this problem is less associated with excessive intake and more so covering up a different, potentially more dangerous, nutrient deficiency.
On the other hand, true excessive consumption of folic acid from supplementation and/or fortified foods is associated with an increased risk of some cancers and a weakened immune system.
It's hypothesized that high folic acid intake accelerates the progression of lesions and increases the activity of natural killer cells. This is because the body only has so much capacity to reduce folic acid to its THF form.
The synthetic form folate – folic acid – is most prevalent in supplements including multivitamins, isolated folate, and B complex vitamins.
Nearly 100% of the folic acid is absorbable when taken without food but reduces to 85% if taken with food. Yet, the body will not absorb the entirety of folic acid if it does not need it. Therefore, it then runs the risk of increasing circulating amounts of unmetabolized folic acid, which is associated with poor health outcomes.
For this reason and because a large percentage of people have the MTHFR gene mutation, it is likely wiser to supplement with the 5-MTHF form of folate. This is the reduced and methylated form, which would benefit those with this gene mutation, as the polymorphism causes too little DNA methylation. The 5-MTHF form is commonly sold under the names Metafolin, Deplin, and Enlyte.
Note that, once again, folinic acid is not a direct folate supplement. Instead, it is used in the treatment of some cancers.
What Does Folate do?
Folate plays many important roles within the body and is so vital because of its interplay with DNA, which then regulates nearly every other metabolic function. Most notably, folate:
• Helps form DNA and RNA
• Assists in protein metabolism
• Breaks down homocysteine
• Produces healthy red blood cells
• Grows the neural tube in vitro
Thus, it is specifically been linked to the following health claims.
Cardiovascular Disease and Stroke
Sufficient intake of folate is necessary to balance homocysteine levels, as it helps metabolize this amino acid into methionine and cysteine. Inadequate folate or b vitamin status can cause homocysteine to accumulate in the blood.
This poses health risks because elevated homocysteine is linked to damaging arteries, leading to blood clots and blood vessel blockages. These can then lead to heart attacks, strokes, and heart disease as well as osteoporosis.
The natural aging process, excessive alcohol intake, and smoking can also elevate homocysteine levels.
Similar to above, elevated levels of homocysteine are also linked to Alzheimer's and dementia. Scientists believe that accumulated homocysteine can cause brain tissue death, the activation of enzymes that harm brain cells and lower methylation activity, which is necessary for healthy DNA.
Interestingly, studies show that folate supplementation in the form of folic acid helps lower homocysteine levels but does not necessarily improve overall cognitive function. This may imply that folic acid is partially sufficient for the treatment of elevated homocysteine but will not improve neurological conditions that are already present.
However, it may still improve cognitive symptoms directly associated with increased homocysteine.
Neural Tube Defects and Other Congenital Anomalies
Of all the health claims regarding folate, this is typically the one people recognize first.
Neural tube defects refer to malformations of the spine such as spina bifida and brain encephalopathy and result from a failure of the neural tube to close between days 21 and 28 of conception. Other congenital anomalies and conditions are also associated with insufficient folate status.
Folate is especially important for DNA and cell division, especially during rapid cell growth like that of a growing fetus. Thus, adequate folate consumption and status significantly reduce the instance of neural tube defects in infants.
Depression and Mood Disorders
Some research shows a correlation between low folate status and increased rates of depression and/or poor responses to antidepressant medication. The exact mechanisms are unclear, but it is likely related to the role of folate in methylation reactions in the brain, neurotransmitter synthesis, and homocysteine metabolism.
In some studies, higher doses of 5-MTHF supplementation in conjunction with specific antidepressants called SSRIs improved depressive symptoms more than SSRIs plus a placebo. However, much more research is needed to determine the safety and viability of supplementation dosing.
Research has not completely established the precise effects of folate on carcinogens. However, scientists hypothesize that this B vitamin influences cancer development related to one-carbon metabolism and DNA replication and cell division.
In fact, numerous studies suggest an inverse association between low folate status and increased risk of bladder, breast, cervical, esophageal, lung, ovarian, pancreatic, stomach, and colorectal cancers.
Studies also show that adequate intakes of folate may suppress cancer progression in the early stages. High doses of folic acid supplementation after cancer has already developed might promote further progression of the cancerous cells.
Autism Spectrum Disorder (ASD)
Some emerging evidence suggests that adequate folate status before and during pregnancy can help reduce the risk of a child having autism spectrum disorder. ASD is characterized by communication and interaction difficulties, limited interests, repetitive behaviors, learning struggles, and other developmental delays.
The exact mechanism is still unknown but likely has to do with DNA methylation which affects neurodevelopment.
Folate is the water-soluble vitamin B9, also called folic acid and methylfolate, although all three are technically different forms. Folate naturally occurs in whole foods, especially green vegetables and organ meats, and is converted into the active form of 5-MTHF. On the other hand, folic acid is synthetic and used in supplements and fortification of food.
Folate plays major roles in DNA methylation and cell division. Adequate folate is associated with reduced risk of fetal neural tube defects, depression, dementia, other cognitive abnormalities, and heart disease.
Conversely, excessive folic acid intake is associated with various health complications like increased risk of cardiovascular disease and Alzheimers. Thus, it is wise to obtain most folate from real foods and to take a 5-MTHF form of folate if supplementing.
Arnarson A. Folic Acid vs. Folate - What's the Difference? Healthline. Written August 19, 2019. https://www.healthline.com/nutrition/folic-acid-vs-folate#bottom-line.
Folate (Folic Acid) – Vitamin B9. Harvard TH Chan. https://www.hsph.harvard.edu/nutritionsource/folic-acid/.
Folate. NIH Office of Dietary Supplements. Updated March 29, 2021. https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/.