Synthetic Folic Acid In Utero Drives Food Allergies

The synthetic vitamin B9 is a common prenatal treatment to prevent birth defects, but may not be as safe as its natural form.

Corinne Keet, MD, MS, PhD

Exposure to the synthetic form of vitamin B9 in utero may be a cause of children developing food allergy.

Folic acid, a commonly recommended neural tube defect prophylaxis for pregnant women that prevents conditions in newborns such as spina bifida, is a synthetic vitamin that requires careful dose regimens. Higher quantities of the treatment could cause it to remain unmetabolized in patients and circulate the blood.

A nested case control study conducted in the Boston Birth Cohort — a large-scale molecular epidemiological study funded by the National Institute of Health in 1998 — found that greater rates of unmetabolized folic acid (UMFA) measured at birth are associated with food allergy development.

Researchers from University of Virginia School of Medicine and Johns Hopkins University Bloomberg School of Public Health measured total folate and 5-methyltetrahydrofolate (5-MTHF) and UMFA concentrations in 1394 children at birth. The pediatric participants’ diet, clinical history and specific-IgE to common food allergens were assessed at stages in their early life.

Based on specific-IgE and clinical history, children were classified as having a food allergy or not. Folate levels were divided into quartiles, and multiple logistic regression was used to estimate clinical accuracy.

Among the observed children, 507 (36%) had food sensitization, as defined by specific-IgE rates of at least 0.35 ku/L. Another 78 children (5.6%) had food allergies.

A subset of children’s 5-MTHF and UMFA were measured at birth (502) and early life (362). Though total folate levels at birth were lower among those who develop food allergies (30.2 versus 35.2 nmol/L; P = 0.02), mean UMFA levels were higher (1.7 versus 1.3 nmol/L; P = 0.001).

Higher quartiles of UMFA were associated more strongly with food allergies (95% CI; 1.9 — 4.7; P = 0.007), while there were no noted associated between early life total folate, 5-MTHF, UMFA levels, and the development of food allergies.

Author Corinne Keet, MD, MS, PhD, said in a statement that increased UMFA rates could be due to increased exposure to synthetic folic acid in utero, or an underlying genetic difference among the children subjects.

“More research is needed to conclude whether mothers should consider different sources of folate like leafy green vegetables, citrus fruits, beans, or lentils instead of synthetic forms of folate,” Keet said.

In an interview with MD Magazine at the 2018 American Academy of Allergy, Asthma & Immunology (AAAAI) and World Allergy Joint Congress in Orlando, FL, Supinda Bunyavanich, MD, an Allergist/Immunologist in the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, said it’s important to explain to expecting mothers that elements outside of their diet could influence pediatric food allergies.

Reasons why kids develop allergies is for a whole combination of factors,” Bunyavanich said. “One is genetic predisposition, which is something you can’t change. You’re either born with a diathesis towards allergy or away from allergy.”

Though it can’t be altered, it can be modulated through deliberate consideration to outside factors, such as environmental exposure, stress, and diet, Bunyavanich said.

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