UMFA stands for unmetabolized folic acid. If left unchecked, UMFA can cause a variety of health problems, but we will go over those later! The majority of folate found within the blood is 5-methyltetrahydrofolate (MTHF), which is not going to harm you; unlike UMFA! There is no need to worry about UMFA if you are getting all your folate from natural sources. However, if you are supplementing or eating a lot of foods fortified with folic acid, you may have a considerable amount of UMFA circulating through your blood!
What Are The Health Consequences Of Too Much Folic Acid And The Build Up Of UMFA?
Your body produces UMFA when it is unable to metabolize folic acid. The rate of folate metabolism is different for everyone, but generally, the body breaks down folic acid slower than folate from natural sources (4). Only people who are supplementing with or consuming folic acid fortified foods are at risk for having UMFA present in their blood. UMFA can cause a variety of problems within the body including (9,11):
Impairment of the immune system
Cancer grows more easily
Lowers iron
Slows cognition
Impairs memory
Why UMFA Builds Up In The Body
Now that you are aware of the health consequences of UMFA, it’s important to know how and why UMFA begins to build up. The body metabolizes and moves folate around the body through several pathways (1,10):
Tissue uptake and storage
Secretion into bile
Reabsorption
Hepatic metabolism
Renal excretion
If any of the listed folate pathways become saturated, the body will begin to build up UMFA within blood serum. Remember that the body has a harder time metabolizing synthetic folic acid compared to naturally occurring folates. See our article on "How Does Folic Acid Supplementing or Fortifying Affect Your Body?" for more information!
The majority of the burden to metabolize folic acid falls onto the liver; where the bulk of the DHFR enzyme (the enzyme responsible for metabolizing folates) is made. The liver has limited capacity to reduce folic acid into folate due to natural biological limitations. If you are supplementing >200ug of folic acid, it will lead to a temporary jump in unmetabolized folic acid in your blood serum (3,6).
3 Steps You Can Take To Reduce UMFA
There are three main ways to reduce folic acid and prevent the build-up of UMFA within your blood:
UMFA is only a problem if you are consuming folic acid on a regular basis. Eating some fortified foods every now and then is not going to kill you, but if you are having trouble becoming pregnant you need every advantage you can get. Reducing consumption of synthetic, and metabolically demanding, folic acid decreases the amount of UMFA found in blood serum — giving you a fertility advantage!
References
Aiso, K., Nagasue, M., Nozaki, T., Shimoda, M., & Kokue, E. (2001). Comparison of dihydrofolate reductase activities for folic acid in pigs and rats using in vivo and in vitro evaluation techniques. Journal of nutritional science and vitaminology, 47(2), 96-101. (4)
Bailey, R. L., Mills, J. L., Yetley, E. A., Gahche, J. J., Pfeiffer, C. M., Dwyer, J. T., ... & Picciano, M. F. (2010). Unmetabolized serum folic acid and its relation to folic acid intake from diet and supplements in a nationally representative sample of adults aged≥ 60 y in the United States. The American journal of clinical nutrition, 92(2), 383-389.
Kelly, P., McPartlin, J., Goggins, M., Weir, D. G., & Scott, J. M. (1997). Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements. The American journal of clinical nutrition, 65(6), 1790-1795.
Mudryj, A. N., de Groh, M., Aukema, H. M., & Yu, N. (2016). Folate intakes from diet and supplements may place certain Canadians at risk for folic acid toxicity. British Journal of Nutrition, 116(7), 1236-1245.
Obeid, R., Kirsch, S. H., Dilmann, S., Klein, C., Eckert, R., Geisel, J., & Herrmann, W. (2016). Folic acid causes higher prevalence of detectable unmetabolized folic acid in serum than B-complex: a randomized trial. European journal of nutrition, 55(3), 1021-1028.
Patanwala, I., King, M. J., Barrett, D. A., Rose, J., Jackson, R., Hudson, M., ... & Jones, D. E. (2014). Folic acid handling by the human gut: implications for food fortification and supplementation. The American journal of clinical nutrition, 100(2), 593-599.
Pfeiffer, C. M., Sternberg, M. R., Fazili, Z., Lacher, D. A., Zhang, M., Johnson, C. L., ... & Berry, R. J. (2015). Folate status and concentrations of serum folate forms in the US population: National Health and Nutrition Examination Survey 2011–2. British Journal of Nutrition, 113(12), 1965-1977.
Pfeiffer, C. M., Sternberg, M. R., Fazili, Z., Yetley, E. A., Lacher, D. A., Bailey, R. L., & Johnson, C. L. (2015). Unmetabolized folic acid is detected in nearly all serum samples from US children, adolescents, and adults. The Journal of nutrition, jn-114.
Plumptre, L., Masih, S. P., Ly, A., Aufreiter, S., Sohn, K. J., Croxford, R., ... & Kim, Y. I. (2015). High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood. The American journal of clinical nutrition, 102(4), 848-857.
Russell, R. M., Rosenberg, I. H., Wilson, P. D., Iber, F. L., Oaks, E. B., Giovetti, A. C., ... & Press, A. W. (1983). Increased urinary excretion and prolonged turnover time of folic acid during ethanol ingestion. The American journal of clinical nutrition, 38(1), 64-70. (5)
Sawaengsri, H., Wang, J., Reginaldo, C., Steluti, J., Wu, D., Meydani, S. N., ... & Paul, L. (2016). High folic acid intake reduces natural killer cell cytotoxicity in aged mice. The Journal of nutritional biochemistry, 30, 102-107.
