Strategies to build stronger bones in Indian children: Challenges for implementation

Indian children & vitamin D deficiency

In a study of apparently healthy 3127 school-going girls from New Delhi, the prevalence of vitamin D deficiency (25(OH)D<50 nmol/l) was 90.8 per cent⁴. Rana et al⁵ recorded a high prevalence of vitamin D deficiency among Indian children based on the analyses of data from the Comprehensive National Nutrition Survey for 2016-2018. They documented Vitamin D deficiency, defined as a serum 25(OH)D <12 ng/ml (<30 nmol/l), in 14, 18, and 24 per cent of children aged 1-4, 5-9, and 10-19 yr, respectively⁴. Greater household income, urban residence, greater Body Mass Index (BMI), school attendance, winter sampling, less than 3 h of physical activity per week, female sex, and a vegetarian diet⁵ were associated with vitamin D deficiency in children. In another study on 338 healthy children from India, vitamin D deficiency/insufficiency was documented in 65.8 per cent of children⁶. Studies from eastern India witnessed a similarly high prevalence of vitamin D deficiency/insufficiency (>70%)⁷. In Kangra and Kullu districts, Himachal Pradesh, the prevalence of vitamin D deficiency (<20 ng/ml; <50 nmol/l), through population-level screening in 1222 healthy children was noted to be 81 and 80 per cent, respectively⁸. Vitamin D deficiency, compounded by poor dietary calcium intake, is the major cause of rickets in children. The Comprehensive National Nutrition Survey recorded that 40 per cent of school-aged children did not consume curd or milk at least once weekly and only six per cent of the children aged 6-23 months were on a minimum acceptable diet⁹.

In a large multicentric study involving 2500 school children from six different States in India, the mean 25(OH)D was noted to be 45.8±23.9 nmol/l, with only 36.8 per cent of children having sufficient serum levels of 25(OH)D (>50 nmol/l)¹⁰. A study from Delhi identified atmospheric pollution as an independent risk factor for high vitamin D deficiency in infants, toddlers and children¹¹. With an exponential increase in urbanization across the country, this problem is expected to worsen. The zenith angle of the sun and the latitudes also have a major role in determining the efficacy of sunlight in forming vitamin D in the exposed skin¹². Although we are exposed to UVB rays at a favourable zenith angle owing to our proximity to the equator, not enough UVB rays reach the skin due to environmental pollution. Vitamin D deficiency is as prevalent in Swedish children as in their Indian counterparts, albeit for a different reason; the Swedish are at a latitudinal disadvantage, unlike us and get exposed to UVB rays at 30 degrees inclination, which is not ideal for cutaneous vitamin D synthesis¹³. Moreover, their exposure to sunlight is less compared to that of Indians. All these studies highlight the public health problem of vitamin D deficiency among children in India, contributing to poor bone health and stunting. A study even highlighted vitamin D deficiency in physicians in India, which was of an equally serious nature¹⁴.

Vitamin D deficiency & bone health

In a systematic review¹⁵, data analyses from 44,992 mother-offspring pairs revealed that vitamin D supplementation to mothers resulted in improved birth length and future growth in under-five children. Another systematic review¹⁶ (7655 children from 7 studies) suggested vitamin D deficiency could lead to dental caries in children. Reportedly, vitamin D deficiency among children also indicated a 22 per cent higher risk of acquiring dental caries as compared to those without¹⁷. A study from Romania evaluating 688 children, revealed that each unit increase in 25(OH)D level significantly reduced the chances of middle third and distal third forearm fractures (OR 1.07 and 1.06, respectively)¹⁸.

A recent systematic review¹⁹ analyzing participant-level data from 120 studies with 5412 children underlined that keeping serum 25(OH)D levels to more than 28 nmol/l (11.2 ng/ml) would offer a protective effect against nutritional rickets for children taking adequate calcium.

Calcium supplementation, exercise & bone health

Apart from ensuring vitamin D sufficiency in children, ensuring adequate daily calcium intake is equally important for children to attain their optimal peak bone mass. In an Randomized Controlled Trial (RCT) from Switzerland, Bonjour et al²⁰ demonstrated that pre-pubertal girls on two food products containing 850 mg of calcium supplements daily for one yr had significantly higher bone mineral density at the radial and femoral bone ends and lumbar spine as compared to the girls receiving placebo. A study from a Canadian University in 1999 demonstrated 9 and 17 per cent greater total body bone mineral content (TB-BMC) for actively exercising boys and girls, respectively, compared to their inactive peers post one year age of peak bone mineral content velocity (PBMCV)²¹.

Vitamin D deficiency & extra-skeletal impact

Gan et al²² in their review, noted a significantly increased likelihood of children having a urinary infection when their serum 25(OH)D was <20 ng/ml²². Moreover, vitamin D deficiency in children has been associated with autoimmune disorders like inflammatory bowel disease (IBD)²³, immune dysfunction and increased risk of infection of the lower respiratory tract²⁴. In a systematic review²⁴ analyzing data from 11 cross-sectional studies (22,196 children), Rouhani et al²⁵ underscored a 50 per cent significant reduction in odds of Metabolic Syndrome (MetS) in children to be associated with the highest vitamin D concentration compared to their counterparts having the lowest concentration of the vitamin. However, it was unclear from the study whether this was a true association or reverse causation.

Vitamin D supplementation & skeletal/extra-skeletal outcomes

In a cohort of 203 underprivileged children and youths with type-1 diabetes (T1DM) from Maharashtra, a western State of India, 200 ml of daily milk supplementation fortified with 1000 IU of vitamin D3 or a daily intake of 500 mg of calcium carbonate tablet along with 1000 IU of vitamin D3 for a year was associated with significantly higher whole body bone mineral content (BMC). The cortical thickness of bones, especially in girls, also increased compared to standard care of no supplementation²⁶. In a systematic review²⁷ (1439 children from 11 studies; 86 per cent female; baseline 25(OH)D 36.3 nmol/l), vitamin D supplementation for a year was associated with an overall improvement in total hip areal bone mineral density (BMD).

Typically the estimated average requirement (EAR) is used to calculate the most likely requirement of a given population, however, the recommended daily allowance (RDA) is used to determine the estimated requirement for individuals at the highest end of the distribution. Hence EAR is always slightly lower than RDA²⁸. Vitamin D supplementation (400 IU/day) is recommended during infancy as the RDA²⁹. The RDA in older children and adolescents is 400- 600 IU/day²⁹. A RCT showed that the children with vitamin D deficiency benefited maximum from the daily supplementation of 2000 IU of vitamin D3³⁰, which was four to five times higher than the dose recommended by the Indian Council of Medical Research (ICMR), Indian Academy of Paediatrics (IAP) or Institute of Medicine (IOM, USA) and thus raised a question about such recommendations. The current guidelines suggest that serum 25(OH)D >20 ng/ml should be maintained in children, especially in high-risk conditions for vitamin deficiency, i.e., chronic kidney or liver disease, and intake of anti-epileptic medications or steroids²⁹. The role of vitamin D as a stand-alone supplement, without adequate calcium and protein intake, remains controversial.

Oral vitamin D supplementation has a high therapeutic window of safety in children. This is of vital importance if we are considering vitamin D fortification. A systematic review³¹ based on analysis of 32 RCTs (8400 children; 0-6 yr) suggested that supplementing vitamin D daily in the range of 1200 to 10,000 IU was well tolerated without any side effects.

Hypervitaminosis D

Hypervitaminosis D and vitamin D intoxication is defined as serum 25(OH)D levels >100 ng/ml and >150 ng/ml, respectively³². Hypervitaminosis D has been seen primarily with parenteral supplementation of supraphysiologic doses of vitamin D³². In contrast with the recommended oral dose, unmonitored and prolonged supplementation with vitamin D with a non-standardized regimen mostly leads to hypervitaminosis D³¹.

Evidence of the impact of vitamin D fortification

A recently published systematic review³³ suggests that adherence to vitamin D supplementation guidelines is challenging in children under five. This highlights the implementation challenges around vitamin D fortification to address the epidemic of vitamin D deficiency in children.

Vitamin D fortified fruit juice has been found to be effective in improving vitamin D deficiency in children with cerebral palsy when administered over four wk³⁴. Serum 25(OH)D in these children improved from 54.1 to 110.3 nmol/l over four wk and was well tolerated without hypercalcemia³⁴. In a systematic review evaluating the impact of food fortification with vitamin D on outcomes in children, the authors analyzed data from 20 different RCTs³⁵. The fortification of grains, cereals, juices, milk, bread, cheese, and curd with vitamin D was compared with no fortification³⁶; food fortification was associated with improvement in 25(OH)D levels by 15.51 nmol/l, with a mean increase of 3 nmol/l for every 100 IU of vitamin D³⁵. In an RCT from the USA involving young children, 12 wk of daily consumption of orange juice providing 200 IU vitamin D and 12 IU vitamin E was effective in increasing 25(OH)D and α-tocopherol concentrations³⁶. Consumption of fortified milk in Morocco was associated with improvement in circulating 25(OH)D levels in children during winters³⁷. Iron and vitamin D status of healthy young European children³⁸ improved in an RCT through micronutrient-fortified young-child formula, and a systematic review³⁹ (5 RCTs, 792 children; 2-11 yr) showed improvement in circulating 25(OH)D levels with dairy products fortified with vitamin D; none experienced hypervitaminosis D or vitamin D intoxication.

Vitamin D fortification

Against the background of the high population prevalence of vitamin D deficiency, particularly in children, there is a strong case for food fortification with the vitamin in India. Fortification of commonly consumed staple foods with vitamin D could be most effective, as evidenced by data from the Western world^40,41. Of note is a recent RCT conducted in New Delhi, where 200 ml milk was fortified with around 240 IU vitamin D2 (ergocalciferol) and supplemented for three months, along with adequate sunlight exposure during winter. However, this did not achieve the sufficient serum 25(OH)D levels particularly in children with vitamin D deficiency⁴². Ergocalciferol was used in this study instead of cholecalciferol as it has a plant-based origin, in contrast to the animal origin of cholecalciferol, which may be an issue with certain sections of the Indian population who are vegans/vegetarians, although cholecalciferol is known to produce better results in terms of serum 25(OH)D levels achieved. This study underpins the importance of using a higher dose of vitamin D (using cholecalciferol rather than ergocalciferol) to mitigate vitamin D deficiency in at-risk children. In a cohort of 290 healthy school girls from Delhi (93.7% having 25(OH)D<50 nmol/l), only 47 per cent were vitamin D sufficient at the end of one year of cholecalciferol supplementation at 60,000 IU monthly or two-monthly, which translated into 1000-2000 IU/day⁴³. These studies highlight that if sufficient doses of vitamin D are not used, the supplementation/ fortification may not be effective.

Vitamin D fortified food for children - way forward

Energy and micronutrient-dense food is needed for children to meet their daily nutritional requirements⁴⁴. Government programmes, especially midday meal programmes in schools, could serve as an indigenous means to provide them with food fortified with vitamin D and other micronutrients. Longer shelf life, ease of preparation and economic considerations will remain central while adopting such an approach. Sattu, a protein-rich Indian food, which is made from roasted flour of cereals and legumes would serve as an ideal candidate for vitamin D fortification from such perspectives⁴⁴. Multicentric pilot studies targeting school-going children supplementing them with vitamin D fortified milk, milk products, or Bengal gram-based laddus, therefore, need to be undertaken urgently to decide upon India specific regimens under such initiatives.