4. Discussion
PDR, inherited hemoglobin disorders
In the present study, neither preventive zinc supplements nor MNP had an effect on IGF1 and IGFBP3 concentrations when provided for 9 months to 6–23 mo old children in rural Lao PDR. However, baseline levels of these biomarkers significantly mediated the linear and ponderal growth response to preventive zinc supplementation. Specifically, the highest response in linear growth to PZ was observed in children with the highest baseline IGF at 18 weeks; whereas the highest ponderal growth response to PZ was observed in children at 36 weeks among children with the lowest IGFBP3 at baseline.Although there is a strong body of scientific evidence linking zinc supplementation to physical growth in children [Another possible reason for the lack of response in IGF1 and IGFBP3 could be that perhaps our study population had underlying conditions that inhibited IGF1 production in quantities necessary to stimulate growth. At baseline median IGF1 and IGFBP3 concentrations were ~46 ng/mL and 2143 ng/mL. These values are ~2–3 times lower than reference values reported in apparently healthy Turkish children 0–6 years of age [It has been documented that inherited hemoglobin disorders, which are highly prevalent in this population [Our findings provide some support for the role of the GH-IGF axis in the nutritional modulation of physical growth. Zinc supplementation improved linear growth among children in the highest IGF tertile and also improved ponderal growth among children in the lowest IGFBP3 tertile. Both high IGF1 and lower IGFBP3 suggest a higher IGF1 bioavailability. Hence, collectively, our findings suggest that zinc supplementation improved physical growth in the children with the highest physiologic growth potential at baseline. This is consistent with evidence from mouse models linking IGF1 bioavailability to linear growth [Finally, it is interesting that the modifying effects of IGF1 and IGFBP3 were apparent at different time points; the mediating effect of IGF1 (on linear growth) and IGFBP3 (on ponderal growth) were apparent at ~18 weeks and 36 weeks, respectively. This pattern may be related to observed longitudinal shifts in the distribution of these markers (A weakness of this study is the lack of growth biomarker data at 18 weeks. In retrospect, it would have been more appropriate to collect this data to allow for a more accurate determination of the changes in IGF1 and IGFBP3 over time, and their association with growth and age. A strength of this study is the individualized randomization protocol and the sample size. To our knowledge, this is the largest randomized trial to date assessing the impact of different zinc formulations on these growth biomarkers, in a population with a high prevalence of stunting.In conclusion, our study suggests that although IGF1 and IGFBP3 did not directly respond to zinc and MNP, both biomarkers may play a critical role in mediating the physical growth response to zinc supplementation.