Why has there apparently been so little research studies on synthetic folic acid?

The short version: the evidence here does not answer whether children should take synthetic folic acid, because no study in this retrieval tested it in children.

The retrieved studies are all in adults or pregnant women. The 2026 trial showing unmetabolized folic acid in 31% of women on standard prenatal doses was in pregnant adults [4]. The 2009 enzyme study showing slow human liver conversion was in adult liver tissue [2]. The 2019 case report of a pseudo-MTHFR syndrome from 5 mg/day was in a 41-year-old woman [1]. None of these tell you what happens in a child's developing system.

What the mechanism suggests is worth weighing. Children have smaller body mass and immature enzyme systems. If adult livers convert synthetic folic acid slowly [2], a child's liver may be even less efficient. The same unmetabolized folic acid that built up in a third of pregnant women on 1 mg/day [4] could accumulate at lower doses in a child. But this is reasoning from adult data, not evidence in children.

The retrieval also found no study defining a safe maximum dose for children. The systematic review showing that women of childbearing age who take folic acid supplements nearly always exceed the 1000 mcg upper tolerable limit [3] is about adults, not children. No pediatric dosing trial, no pediatric safety study, and no pediatric long-term outcome study appears in these records.

My call: the evidence does not support giving synthetic folic acid to children at any dose, because no pediatric safety or dosing study was retrieved. The adult data raises concerns about unmetabolized folic acid accumulation, and those concerns apply more strongly to smaller bodies. Confidence: low — the retrieval simply did not capture pediatric studies, which may exist elsewhere.