‍Folate is an important vitamin involved in critical processes in the body. Folate is so important that in 1998 the United States Food and Drug Administration (FDA) began requiring food manufacturers to fortify our food with a synthetic form of folate. This article will discuss what folate is, including its role in the body, deficiency causes, and symptoms. We’ll then discuss folate testing and sources of folate, including dietary sources and supplements.

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What is Folate (Vitamin B9)?

Folate, also known as vitamin B9, is a water-soluble vitamin. Folate is processed in the gastrointestinal tract, where enzymes will break it down and convert it into metabolically active forms; the majority of folate in the blood is in the 5-methyltetrahydrofolate (5-MTHF) form.

What is Folate’s (Vitamin B9’s) Role in The Body?

Folate plays a role in DNA and amino acid metabolism.

DNA Metabolism

Folate plays a role in DNA metabolism in a couple of different ways. First, folate is required for the creation of DNA from its precursors, purines, and thymidine. Second, folate is necessary for the formation of S-adenosylmethionine (SAM). SAM is required for many reactions in the process of methylation. Methylation affects many systems in the body, including hormone production, DNA creation, and detoxification. In addition to DNA creation, methylation also affects the function of DNA by influencing cell differentiation and genetic expression.

One of the most well-known enzymes in the methylation process is 5,10-methylenetetrahydrofolate reductase (MTHFR). This enzyme is composed of folate, as its name implies, and it also converts folate into its active form in the body.

Amino Acid Metabolism

Metabolism of the amino acids methionine, cysteine, serine, glycine, and histidine is dependent upon folate. Methionine is made from homocysteine, and lack of folate will inhibit this conversion, leading to higher levels of homocysteine. Elevated homocysteine has been associated with blood clots leading to strokes and heart attacks, and dementia. Cysteine is a precursor to the body’s most potent antioxidant, glutathione. Serine and glycine function as neurotransmitters in the brain. Histadine protects nerve cells and plays a role in blood cell creation and growth and repair of damaged tissues; it's also a precursor to the neurotransmitter histamine.

What Causes Folate (Vitamin B9) Deficiency?

Certain conditions can increase the risk of folate deficiencies. People with alcohol use disorder can have folate deficiencies, as they tend to have poor diets, and alcohol intake can inhibit absorption and cause increased excretion of dietary folate. Pregnant women are also at an increased risk of folate deficiency, as folate is in high demand for the creation of DNA. Those with malabsorptive disorders, including celiac disease and inflammatory bowel disease (IBD), can be at an increased risk of folate deficiency. Conditions that cause lower acid secretion in the stomach, such as atrophic gastritis and gastric surgery, can lead to lower folate absorption. Lastly, those who have a specific type of polymorphism in the methyltetrahydrofolate reductase (MTHFR) gene can lead to lower folate levels. Polymorphisms mean the gene is altered, which will affect its functioning. The MTHFR polymorphism C667T inhibits the conversion of folate into its active form in the body.

Folate (Vitamin B9) Deficiency Symptoms

Folate deficiency can lead to angular cheilitis (inflammation and cracking skin on the corners of the mouth), hair, skin, and nail changes, diarrhea, and cognitive changes, including memory loss, confusion, and trouble concentrating. High levels of homocysteine are also common in a folate-deficient state. Additionally, folate deficiency can lead to folate deficiency anemia.

‍Anemias are characterized as not having enough red blood cells to transport oxygen throughout the body. Folate deficiency causes megaloblastic anemias, which means that the red blood cells enlarge. Symptoms specific to folate deficiency anemia are:

• Fatigue
• Dizziness
• Cold hands and feet
• Headaches
• Shortness of breath
• Pale skin
• Weakness
• Irregular heart rate

In pregnant women, lack of folate can lead to neural tube defects, fetal growth problems, preterm delivery, and low birth weight. Neural tube formation begins during the third and fourth weeks of pregnancy. Failure of the neural tube to form properly, as can be caused by lack of folate, can lead to morbidity and mortality.

How to Test Folate (Vitamin B9) Levels

Blood folate levels can be checked, as offered in the Folate test by Access Medical Laboratories. Serum folate levels below three micrograms per liter (mcg/L) indicate a folate deficiency. Additionally, folate levels can be checked through a red blood cell (RBC) folate test, which represents long-term folate status. Vibrant America offers an RBC folate test, and levels less than 150 mcg/L indicate a folate deficiency.

If looking for a folate deficiency anemia, or if levels of folate are checked and low, a complete blood count (CBC), such as the CBC test offered by Access Medical Laboratories and methylmalonic acid (MMA) test, as offered in the MMA test by Vibrant America, should also be considered. These tests can help to diagnose anemia. Additionally, megaloblastic anemia, the type of anemia seen in folate deficiencies, can also be caused by B12 deficiencies. MMA is a marker of B12 status and thus can help to differentiate if folate or B12 is causing the anemia in the event that folate levels have not been checked yet.

Lastly, homocysteine levels can be measured, as offered in the Homocysteine test by Access Medical Laboratories, to give insight into folate levels. Higher homocysteine levels can be an indicator of folate deficiency, although kidney dysfunction and other nutrient deficiencies can also cause elevated homocysteine, and thus it should not be used as an isolated marker to diagnose folate deficiencies.

Folate levels can also be found on micronutrient tests such as the Spectracell Micronutrient panel.

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How to Get Enough Folate (Vitamin B9) from Your Diet

The Food and Nutrition Board (FNB) at the National Academies of Science, Engineering, and Medicine has created Dietary Reference Intakes (DRIs) for vitamins and minerals. Recommended Dietary Allowances, or RDAs, are one such DRI. RDA is defined as the average daily intake required to meet nutritional adequacy in 97-98% of the healthy population. When there is insufficient evidence to form RDAs, Adequate Intake (AI) levels are formed. AIs are defined as levels assumed to reach nutritional adequacy.

There is a significant discrepancy between the bioavailability of folate in foods versus folic acid, the synthetic form used in food fortification and often found in supplements. Folate in foods has an absorption rate of about 50%, whereas folic acid’s absorption rate is 85% when taken with or in foods.

The FNB established DRIs of folate as micrograms of dietary folate equivalents (DFEs), defined as:

1 mcg DFE = 1 mcg food folate

1 mcg DFE = 0.6 mcg folic acid from fortified foods or dietary supplements taken with foods

1 mcg DFE= 0.5 mcg folic acid from dietary supplements taken away from foods on an empty stomach

RDA of Folate

AIs were established for birth through 1 year. The AI for males and females from birth to six months is 65 mcg DFE. The AI for males and females from seven months to 1 year is 80 mcg DFE.

Pregnant and lactating women often have different DRI values due to their different nutritional needs. For pregnant women aged 14 and above, the RDA of folate is 600 mcg; lactating women 14+ years have an RDA of 500 mcg.

It’s important to note that women of childbearing age are often not getting enough folate. Because of this, it is recommended that all women of childbearing age receive an extra 400 mcg/day of folic acid in the form of supplements or folic acid-fortified foods in addition to their normal dietary intake.

Sources of folate include food and supplements.

Due to the importance of folate on neural tube formation, the FDA decided to require manufacturers of food products to have 140 micrograms (mcg) of folic acid, the synthetic form of folate, per 100g of food. Examples of food products enriched with folic acid are enriched breads, cereals, flour, cornmeal, pastas, rice, and other grain products.

Food Sources of Folate

Folate (Vitamin B9) Supplements

Folate is found in multivitamins, b-complexes, and stand-alone supplements. There are different forms of folate found in supplements. The most common form of folate is the synthetic form of folic acid. Adult supplements typically contain 400 to 800 mcg of folic acid (680 to 1,360 DFE), and children's supplements contain 200 to 400 mcg of folic acid (340 to 680 DFE). Folic acid has an absorption rate of around 85% when taken with food; folic acid taken without food increases this rate to 100%.

Folate, in its active form of 5-MTHF, can also be found in supplements. The Food and Drug Administration requires supplement companies to have a conversion factor of 1.7 or lower for folic acid to 5-MTHF in supplements.

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Summary

Folate, or vitamin B9, is an essential vitamin vital for the formation and function of DNA and many biochemical pathways. Adequate folate intake should be monitored in all patients to ensure a deficiency is not present. Testing folate levels can definitively determine adequate status. In the presence of deficiency or low-normal levels, food sources may help to replenish folate status in the body. However, supplementation may also be necessary depending on the level to avoid further depletion and deficiencies.