D-chiro-inositol is more effective than myo-inositol in preventing folate-resistant mouse neural tube defects

BACKGROUND: Among mouse genetic mutants that develop neural tube defects (NTDs), some respond to folic acid administration during early pregnancy, whereas NTDs in other mutants are not prevented. This parallels human NTDs, in which up to 30% of cases may be resistant to folic acid. Most spina bifida cases in the folic acid-resistant `curly tail' mouse can be prevented by treatment with inositol early in embryonic development. Here, the effectiveness and safety during pregnancy of two isomers, myo- and D-chiro-inositol, in preventing mouse NTDs was compared. METHODS AND RESULTS: Inositol was administered either directly to embryos in vitro, or to pregnant females by s.c. or oral routes. Although D-chiro- and myo-inositol both reduced the frequency of spina bifida in curly tail mice by all routes of administration, D-chiro-inositol consistently exhibited the more potent effect, reducing spina bifida by 73-86% in utero compared with a 53-56% reduction with myo-inositol. Pathological analysis revealed no association of either myo- or D-chiro-inositol with reduced litter size or fetal malformation. CONCLUSIONS: D-chiro-inositol offers a safe and effective method for preventing folic acid-resistant NTDs in the curly tail mouse. This raises the possibility of using inositol as an adjunct therapy to folic acid for prevention of NTDs in humans.