Patient Presentation
A 10-year-old male came to clinic for his health supervision visit. His parents had no concerns other than wanting testing done to make sure he has “enough folate” because they were eating a vegetarian diet. The family did eat dairy and egg products but no “flesh” animal products nor fish. They did eat homemade and commercially made breads, pasta and corn tortillas. He would eat a relatively wide variety of leafy greens, nuts, seeds, beans, pulses and almost any fruit. “I won’t eat brussel sprouts or kale though. They’re bitter,” he complained. They did not use any multivitamin supplementation. The past medical history was negative. He had normal screening laboratory testing at age 1 and 2 for anemia and lead.

The pertinent physical exam showed a healthy male with normal vital signs. His weight was at the 15% and height at the 50%.
His examination was normal.

The diagnosis of a healthy male vegetarian was made. The pediatrician questioned the parents about folate. “It sounds like he has a pretty wide range of foods that have folate in them. Is it maybe ferritin you are worried about as that could be linked to iron deficiency which is more common in vegetarian diets?” “Yes, that’s what I meant. I got it mixed up. It’s one of those vitamins and minerals that starts with “F,” said the mother, “I just want to make sure that he’s getting what he needs to be healthy.” The pediatrician included a complete blood count, ferritin and Vitamin D level to the regular screening lipid panel planned for that day. “I expect these will be normal but it is good to check and also you should continue to eat a good range of foods. As you will eat dairy products that will be helpful for the calcium, Vitamin D and protein you need now and especially as you become a teenager,” he counseled. The laboratory testing was normal.

Discussion
Folate is a water soluble B vitamin that is used as cofactors for enzymes, particularly those for DNA and RNA synthesis. Tetrahydrofolates and dihydrofolates are the physiological forms of folates but are unstable and undergo degradation during food preparation. Folic acid is an oxidized form of folate that is synthesized, highly stable, and inexpensive and thus is used to fortify many flour and grain foods around the world. Folic acid is also more bioavailable (85%) than folate (50%). The term folic acid will be used in the rest of this discussion.

Folic acid deficiency can result in megaloblastic anemia (seen with both folic acid and B12(cobalamin) deficiency), and dermatological and skin ulcerations. In pregnant women it is associated with neural tube defects (NTD), fetal growth retardation, low birth weight and preterm delivery. Folic acid deficiency is associated with overall poor nutrition, such as people with alcohol use or malabsorption disorders, and not usually seen in isolation. Low folate has been linked to some problems such as cancer and cognitive issues such as dementia and possibly depression. Potential risks of excessive folic acid are less well documented but some “…studies suggesting that high folic acid intake may under certain conditions promote cancer, interact with medications and impair f[e]tal development.” Some animal studies also show potential hepatic damage or epilepsy.

Learning Point
Folic acid is found in green leafy and other vegetables, beans, nuts, peas, grains, fruits and fruit juices, and also meat, poultry, dairy products, eggs and seafood. Asparagus, brussel sprouts, spinach, and liver have some of the highest folic acid levels.

Neural tube defects (NTDs) are caused by failure of the neural tube to close properly. Caudal defects are more common than cephalic, as cephalic defects result in more severe problems such as anencephaly. The incidence is 1-3 per 1000 births worldwide and in the US is estimated at 1:3000.

Fortification of the food supply in many countries has decreased the prevalence of NTDs, but it is “…estimated that 75% of the folic acid preventable NTDs are not prevented due to inadequate or absent fortification….” Fortification programs can be mandatory or voluntary. Mandatory programs “…have more uniform exposure of a given micronutrient across individuals in a population compared with voluntary fortification programs both in coverage and exposure level.” In the US, foods that have the “enriched” label must be fortified with folic acid since 1998. Fortification of 140 microgram/100 gram of flour/grain product is 2x that lost in food processing and much below the 1000 microgram/day recommended limit. This amount of fortification brings the estimated amount in a general adult diet to ~400 micrograms/day which is the amount recommended for women of childbearing age to help prevent NTDs.

Also folic acid “…in foods for infants and young children for over 50 years [has been used] without any evidence of harm when intake levels are below the [recommended levels]. “

Folic acid and its food supplementation within the recommended levels has been shown to be safe, and the current literature supports fortification programs to prevent NTDs.

Questions for Further Discussion
1. What is the recommended dietary allowance of folic acid for different age groups? A listing can be found here
2. What types of foods do vegetarians need to eat to maintain proper nutrition? A review can be found here
3. What preventative health care should pregnant women receive to help prevent health problems for their babies?
4. How common is iron deficiency anemia in the pediatric population and how do you screen for it? Cases can be found here
5. Why are brassica vegetables bitter tasting for some individuals?

Related Cases

Disease: Folic Acid | Neural Tube Defects

Symptom/Presentation: Health Maintenance and Disease Prevention

Specialty: Nutrition / Dietetics

Age: School Ager

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Folic Acid and Pregnancy and Nutrition.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Ross ME, Mason CE, Finnell RH. Genomic approaches to the assessment of human spina bifida risk. Birth Defects Res. 2017;109(2):120-128. doi:10.1002/bdra.23592

Patel KR, Sobczynska-Malefora A. The adverse effects of an excessive folic acid intake. Eur J Clin Nutr. 2017;71(2):159-163. doi:10.1038/ejcn.2016.194

Field MS, Stover PJ. Safety of folic acid. Ann N Y Acad Sci. 2018;1414(1):59-71. doi:10.1111/nyas.13499

Office of Dietary Supplements – Folate. Accessed August 9, 2024. https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa<