Table 7.

Vitamin D research opportunities

Health outcomes
Pregnancy outcomes
Numerous studies have suggested that vitamin D affects pregnancy and birth outcomes,10 but evidence is conflicting and there is no consensus on the optimal dose of vitamin D supplementation to maximize the prenatal and/or postpartum maternal and infant benefits.
Research need: Establish the dose-dependent effects of vitamin D supplementation on maternal and infant outcomes, such as pre-eclampsia, gestational diabetes, preterm birth, SGA, postnatal infant growth, and infant rickets.
It is expected that the effect of vitamin D on skeletal outcomes (including linear growth and the risk of rickets in infants) depends on calcium nutriture, and may interact with other micronutrients.
Research need: Investigate the relationship between vitamin D and other nutrients, including calcium, vitamin A, folate, and iron as they relate to pregnancy outcomes and risk ofrickets.
There is concern that recommending infant supplementation may conflict with breastfeeding support and promotion efforts, and some mothers are concerned about supplementing infants. Maternal supplementation is one alternative, but the optimal dose to supplement mothers for the health of their infants is not known.
Research need: Determine the optimal dose, regimen, safety, and efficacy for maternal supplementation to optimize 25(OH)D and prevent rickets in breastfed infants.
Respiratory outcomes
It has been hypothesized that free (nonprotein bound) 25(OH)D plays a role in the immune response in respiratory infections, but this hypothesis has not been sufficiently studied.
Research need: Investigate whether concentrations of free and/or bioavailable 25(OH)D correlate more tightly with respiratory outcomes than total 25(OH)D.
Vitamin D supplementation has shown some efficacy in prevention of URIs, but the effects of supplementation on prevention of LRIs and active TB are not yet known.
Research need: Determine ifdaily or weekly vitamin D supplementation can prevent LRIs or active TB.
The immune-modulating effects ofvitamin D suggest that it could be used as an adjunctive therapy for treating some respiratory diseases, but this has not been thoroughly tested.
Research need: Establish the efficacy of vitamin D as an adjunctive therapy for treating LRIs or for patients with multidrug-resistant TB.
Much of the testing on vitamin D in asthma to date has involved patients with mild-to-moderate asthma, in which vitamin D can reduce asthma exacerbations.119,121 Whether this also applies to those with more severe asthma is not known.
Research need: Determine whether vitamin D can reduce asthma exacerbations in patients with severe asthma.
In studies of vitamin D supplementation in asthma, the greatest benefit has been associated with those patients who had the lowest 25(OH)D status at baseline (<25 nmol/L).119 However, more studies are needed to determine if vitamin D supplementation can benefit those with lesser degrees of deficiency at baseline.
Research need: Investigate the benefits ofvitamin D in asthma treatment to assess whether it is restricted to those with lower vitamin D status.
Prevalence and surveillance of vitamin D deficiency
Prevalence
There is a general lack of 25(OH)D data in LMICs,57 but the limited existing data suggest that vitamin D deficiency may be a significant problem in many countries. More data are needed to establish the extent of vitamin D deficiency.
Research need: Increase assessment of25(OH)D as a biomarker of vitamin D deficiency in nationally representative surveys in LMICs.
There are limited data regarding vitamin D intake and exposure in LMICs, and improving these estimates will aid in identifying countries where a 25(OH)D assessment survey is necessary.
Research need: Improve estimates ofvitamin D and calcium intake and exposure in LMICs to identify settings where further assessment ofvitamin D status is warranted.
Surveillance
As nutritional rickets is an indicator of a larger vitamin D deficiency prevalence, expanding rickets surveillance, especially in LMICs, would improve vitamin D deficiency data and highlight areas in greatest need of a status survey or an intervention.
Research need: Identify regions with the greatest prevalence of vitamin D deficiency by expanding rickets surveillance to include case reports and validated clinical signs, especially in LMICs. Consider the potential use of serum ALP as a screening biomarker for rickets.
The increasing recognition of the role of vitamin D in immune and cardiovascular health suggests that there maybe an underappreciated effect of vitamin D deficiency on child mortality.
Research need: Better understand the effects oflow vitamin D status and vitamin D supplementation on child mortality, especially in low-income settings, given that vitamin D is a known immune modulator and that low vitamin D increases the risk ofrespiratory infections, and that there may be unknown consequences of vitamin D deficiency.
Vitamin D interventions
Fortification
Cofortification of foods with both vitamin A and vitamin D presents a cost-effective method for fortification in countries with an existing vitamin A fortification program.176 However, it is unclear whether there are interactions between the two micronutrients that may affect their efficacy, bioavailability, and/or stability.
Research need: Establish the efficacy of cofortification with vitamins D and A.
Calcium and vitamin D are highly dependent on each other for optimal bone health. However, in many LMICs, it is often not practical to fortify dairy products, which naturally contain calcium (either because of low consumption or small-scale production). As calcium can dramatically affect the organoleptic properties of the vehicle, acceptable alternatives to ensure adequate calcium and vitamin D intake are needed.
Research need: Assess alternative methods ofcalcium and vitamin D codelivery, especially in countries where dairy consumption is low.
Bio-addition is a potentially low-cost alternative for increasing the vitamin D content in foods.173 However, these techniques need further development and have not been assessed for their suitability in LMICs.
Research need: Develop methods to increase the vitamin D content offoods through bio-addition.
Dosage and safety of supplementation
Vitamin D supplementation during routine vaccination provides a good opportunity to ensure that children receive adequate vitamin D, but the efficacy of delivering relatively large doses with vaccines has not been tested.
Research need: Determine the safety and effectiveness of delivering vitamin D with childhood vaccinations.
Awareness and education
Educating the public about the current recommendations remains an important and ongoing task to ensure the success and public acceptance of interventions, including supplementation and fortification.
Research need: Design and test approaches to enhancing awareness among the general public of vitamin D recommendations and the impact of vitamin D on health outcomes.
Ensuring that parents and caregivers of infants and children are well informed about the health consequences of vitamin D deficiency and current supplementation recommendations (maternal, infant, and child) as important strategies to improve adherence and ultimately prevent rickets.
Research need: Develop and evaluate social and behavior change strategies to improve adherence to infant and childhood vitamin D supplementation.