The PONTI study: inositol and prevention of NTDs
Some cases of NTD can be prevented by supplementation with folic acid before and during early pregnancy, but it is increasingly apparent that a significant proportion of NTDs fail to respond to FA. Most programmes of voluntary supplementation and folic acid food-fortification have observed a reduction in NTD prevalence of less than 50%. As a result, NTDs continue to occur at an average frequency of 0.5-1.0 per 1000 established pregnancies, worldwide. We have explored the possibility that inositol, a vitamin-like molecule with a key role in cellular metabolism, has a NTD-preventive action that is independent of folic acid. If confirmed, this could lead to a combined approach to primary prevention of NTDs, involving both folic acid and inositol supplements.
In previous work, the Neural Tube Group has:
- Established that both myo- and D-chiro-inositol can significantly reduce the frequency of spinal NTDs in curly tail (Grhl3 gene) mice, both by dosing the pregnant female, and by direct treatment of embryos in culture (Greene & Copp, 1997; Cogram et al, 2002).
- Shown inositol therapy to be safe in mouse pregnancy, with no adverse effects noted in either mothers or fetuses (Cogram et al, 2002).
Demonstrated that inositol acts via activation of protein kinase C, with a specific requirement for PKC isoforms beta and gamma (Cogram et al, 2004).
- Developed a mass-spectrometry-based assay for inositol in biological samples (Leung et al, 2011).
- The PONTI pilot study (Prevention of Neural Tube Defects by Inositol): UK women with a history of NTD pregnancy were recruited into a double-blind, randomised controlled trial of myo-inositol supplementation before and during early pregnancy. The pilot study was designed to provide information on the following primary outcomes:
The PONTI study was published in February 2016 (Greene et al, Br J Nutr). Its results are:
For details of trial registration go to https://clinicaltrials.gov/ct2/show/NCT00452829?term=ponti&rank=1
For the original PONTI clinical trial protocol click here (PDF)