Folate: What the Test Shows and Why It Matters for an Athlete

Folate rarely comes into the focus of athletes, although normal blood formation is impossible without it. The editorial team explains what the folate test measures, how the serum indicator differs from the red-cell one, and in which situations an athlete should take it.

Folate and its role in the body

Folate is a group of compounds of vitamin B9. In nature they are found in leafy vegetables, legumes, liver and citrus fruits, while the synthetic form — folic acid — is used in supplements and to fortify flour in many countries. In the body all forms are converted into the active derivatives of tetrahydrofolate.

The main function of folate is the transfer of one-carbon groups. They are needed for the synthesis of nucleotides, that is, for building DNA, and for methylation, in particular the conversion of homocysteine into methionine together with vitamin B12. That is why rapidly dividing cells are most sensitive to a lack of folate.

For an athlete the most important consequence is blood formation. Every day the body forms a huge number of new red blood cells, and with folate deficiency megaloblastic anemia develops, just as with a lack of B12. A reduced ability of the blood to carry oxygen directly hits endurance.

In addition, folate participates in the renewal of intestinal mucosa cells, immune cells and tissues recovering after training-induced damage. For women of reproductive age, adequate folate status is critically important for preventing neural tube defects in the fetus.

What the test shows: serum or red blood cells

Laboratories offer two main tests: serum (or plasma) folate and red blood cell folate. They answer different questions, and understanding this difference is the key to correct interpretation.

Serum folate reflects the recent intake of the vitamin — over the past days or weeks. It can decrease after several weeks of poor nutrition and quickly rise after a single supplement dose or a meal rich in folate. That is why for this test it is important to give blood fasting.

Red blood cell folate reflects the reserve in the tissues. A red blood cell receives folate during its formation and stores it throughout its life — about 120 days. Thus this indicator characterizes the status over the preceding 3–4 months and depends less on recent meals.

The World Health Organization, in a 2015 document, gives deficiency thresholds: serum folate below 10 nmol/L (4 ng/mL) and red blood cell folate below 340 nmol/L (151 ng/mL). For women of reproductive age the WHO additionally indicates a red blood cell folate level above 906 nmol/L (400 ng/mL) as optimal for preventing neural tube defects at the population level.

Why the test is important specifically for an athlete

The need for folate in athletes, according to the position of the ACSM, the Academy of Nutrition and Dietetics and Dietitians of Canada (2016), is usually covered by a balanced diet. However, in real practice there are several scenarios in which the status comes under threat.

• restricted diets with a minimum of vegetables and legumes, typical of "cutting" or mass gain on a monotonous diet;
• low energy availability, when the total amount of food is insufficient;
• regular alcohol consumption, which impairs the absorption and metabolism of folate;
• intestinal diseases with impaired absorption;
• intake of folate-antagonist drugs (methotrexate, some anticonvulsants, trimethoprim).

Athletes with anemia are often examined only for iron. However, if the complete blood count shows an increased volume of red blood cells, it is logical to check folate and B12 specifically. A mixed deficiency is also not uncommon.

For female athletes planning pregnancy, the red blood cell folate test helps assess whether the reserve is sufficient at the moment of conception. However, the recommendation to take folic acid before conception applies regardless of the test, as prescribed by a doctor.

Finally, folate together with B12 determines the level of homocysteine. If homocysteine is elevated, the folate test helps to understand the cause.

How to prepare and what to keep in mind

For serum folate the standard requirements are fasting for 8–12 hours without food and without taking vitamin supplements on the day of the test. Otherwise the result will reflect breakfast rather than status.

Hemolysis of the sample falsely raises serum folate, because its concentration in red blood cells is much higher than in plasma. If the laboratory reports hemolysis, it is better to retake the test.

Folate should be interpreted only together with B12. In B12 deficiency, folate "gets stuck" in a form the cell cannot use — this is the so-called "folate trap", because of which serum folate may be normal or even elevated.

Folate immunoassays, like other similar tests, can be sensitive to high doses of biotin; the FDA advises informing the doctor and the laboratory about its intake.

Editorial conclusions

Folate is needed for DNA synthesis, blood formation and homocysteine metabolism. For an athlete its shortage means a risk of anemia and reduced endurance.

Serum folate reflects recent nutrition, while red-cell folate reflects reserves over several months. Both indicators should be assessed together with B12 and the complete blood count.

The test is most useful in cases of restricted diets, alcohol, intestinal diseases, intake of folate antagonists and macrocytic anemia.

We also recommend reading our materials on folate deviations from the norm, on the vitamin B12 test and on preparing for the homocysteine test.

References

1. World Health Organization. Serum and red blood cell folate concentrations for assessing folate status in populations. Vitamin and Mineral Nutrition Information System. Geneva: WHO; 2015.
2. Bailey LB, Stover PJ, McNulty H, et al. Biomarkers of Nutrition for Development — Folate Review. J Nutr. 2015;145(7):1636S–1680S.
3. Devalia V, Hamilton MS, Molloy AM; British Committee for Standards in Haematology. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496–513.
4. Thomas DT, Erdman KA, Burke LM. American College of Sports Medicine Joint Position Statement. Nutrition and athletic performance. Med Sci Sports Exerc. 2016;48(3):543–568.
5. Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999;19:217–246.
6. U.S. Food and Drug Administration. The FDA warns that biotin may interfere with lab tests: FDA Safety Communication. 2017 (updated 2019).