Effect of Calcium and Vitamin D Supplementation (Dairy vs. Pharmacological) on Bone Health of Underprivileged Indian Children and Youth with Type-1 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Bone health is affected by chronic childhood disorders including type-1 diabetes mellitus (T1DM). We conducted this randomized controlled trial with the objective of investigating the effect of 1-year supplementation of vitamin-D with milk or with pharmacological calcium on bone mass accrual in underprivileged Indian children and youth with T1DM. METHODS: 5 to 23year old (n = 203) underprivileged children and youth with T1DM were allocated to one of three groups: Milk (group A-received 200 ml milk + 1000 international unit (IU) vitamin-D3/day), Calcium supplement (group B-received 500 mg of calcium carbonate + 1000 IU of vitamin-D3/day) or standard of care/control (group C). Anthropometry, clinical details, biochemistry, diet (3-day 24-h recall), physical activity (questionnaires adapted for Indian children) and bone health parameters (using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography- DXA and pQCT respectively) were evaluated at enrolment and end of 12 month intervention. RESULTS: Total body less head(TBLH) bone mineral content (BMC(g)) and bone mineral density (BMD(gm/cm2)) were significantly higher at end of study in girls in both supplemented groups (TBLHBMC-A-1011.8 ±â€¯307.8, B-983.2 ±â€¯352.9, C-792.8 ±â€¯346.8. TBLHBMD-A-± 0.2, B-0.8 ±â€¯0.2, C-0.6 ±â€¯0.2, p < 0.05). Z score of lumbar spine bone mineral apparent density of supplemented participants of both sexes was significantly higher than controls (Boys- A-0.7 ±â€¯1.1, B-0.6 ±â€¯1.4, C- -0.7 ±â€¯1.1; Girls- A-1.1 ±â€¯1.1, B-0.9 ±â€¯3.4, C- -1.7 ±â€¯1.3, p < 0.05). A significantly higher percentage increase was found in cortical thickness in girls in both supplemented groups (A-17.9 ±â€¯28.6, B-15.3 ±â€¯16.5, C-7.6 ±â€¯26.2); the differences remained after adjusting for confounders. CONCLUSION: Supplementation with milk or pharmacological calcium (+vitaminD3) improved bone outcomes-particularly geometry in children with T1DM with more pronounced effect in girls. Pharmacological calcium may be more cost effective in optimising bone health in T1DM in resource limited settings.

Effect of Yoga or Physical Exercise on Muscle Function in Rural Indian Children: A Randomized Controlled Trial.

BACKGROUND: Synergistic effects of yoga or physical exercise (PE) along with protein supplementation on children's muscle function in rural India have not been studied. Hence, we aimed to study the effect of yoga and PE along with protein supplementation on muscle function in healthy 6- to 11-year-old rural Indian children post 6 months of intervention. METHODS: A randomized controlled trial on 232 children, recruited into 3 groups, each receiving 1 protein-rich ladoo (148 kcal, 7 g protein/40 g ladoo-an Indian sweet snack) daily and performing (1) yoga (n = 78) for 30 minutes 5 times per week, (2) PE (n = 76) for 30 minutes 5 times per week, or (3) control group (n = 78) no additional exercise. Maximum power, maximum voluntary force (Fmax), and grip strength (GS) were measured. Data were analyzed using paired t tests and a 2-way mixed analysis of variance with post hoc Bonferroni adjustment. RESULTS: GS, maximum power, and Fmax within yoga group increased significantly (P < .05) from baseline to endline. GS and Fmax increased significantly within PE group postintervention (P < .001). In controls, GS increased (P < .05) at endline. No significant effect of the intervention was observed on the change in maximum power (P > .05) postintervention. The 2 exercise groups showed significant increase in Fmax compared with the control group (P < .05). Similarly, increase in GS was significantly higher in both the exercise groups compared with the control group (P < .05). No significant difference was observed in change in muscle function between the 2 exercise groups (P > .05). CONCLUSIONS: Structured physical activity along with protein supplementation resulted in improved muscle function in children. Yoga and PE showed a comparable impact on muscle force.

Vitamin D status and determinants in Indian children and adolescents: a multicentre study.

Studies performed on Indian children to assess vitamin-D status have been on small sample sizes, limited to specific geographical locations and used non-standard methods to measure 25(OH)D3. This multicentre study assessed 25(OH)D3 concentrations from dried blood spots (DBS) in 5-18-year-old Indian children and adolescents using a standardized protocol and identified factors contributing towards vitamin D deficiency. Cross-sectional, observational school-based study was conducted by multi-stage stratified random sampling. A city and nearby village were selected from 6 Indian states covering wide geographical areas. Demography, anthropometry, body-composition, dietary-intakes and DBS samples were collected. 25(OH)D3 was assessed from DBS using Liquid chromatography with tandem-mass spectrometry. Vitamin-D status was assessed in 2500 children; with additional data collected on a subset (n = 669) to assess predictors. Mean vitamin-D concentration was 45.8 ± 23.9 nmol/L, 36.8% of subjects had sufficient vitamin-D (> 50 nmol/L); rural subjects and boys had higher concentrations (p < 0.05). On regression analysis, younger age, female-gender, overweight and urban residence significantly contributed to deficiency. More than half the Indian children/adolescents were vitamin-D deficient or insufficient. Our study reinforces vitamin-D deficiency as a major public health problem and the need for supplementation, food fortification and educating the population as initiatives required to improve sufficiency status.

Indian Academy of Pediatrics Revised (2021) Guidelines on Prevention and Treatment of Vitamin D Deficiency and Rickets.

JUSTIFICATION: The emerging literature on prevalence of vitamin D deficiency in India, prevention and treatment strategies of rickets, and extra-skeletal benefits of vitamin D suggest the need for revising the existing guidelines for prevention and treatment of vitamin D deficiency in India. OBJECTIVES: To review the emerging literature on vitamin D prevalence and need for universal vitamin D supplementation. To suggest optimum vitamin D therapy for treatment of asymptomatic and symptomatic vitamin D deficiency, and rickets. To evaluate the extra-skeletal health benefits of vitamin D in children. PROCESS: A National consultative committee was formed that comprised of clinicians, epidemiologists, endocrinologists, and nutritionists. The Committee conducted deliberations on different aspects of vitamin D deficiency and rickets through ten online meetings between March and September, 2021. A draft guideline was formulated, which was reviewed and approved by all Committee members. RECOMMENDATIONS: The group reiterates the serum 25-hydroxy vitamin D cutoffs proposed for vitamin D deficiency, insufficiency, and sufficiency as <12 ng/mL, 12-20 ng/mL and >20 ng/mL, respectively. Vitamin D toxicity is defined as serum 25OHD >100 ng/mL with hypercalcemia and/or hypercalciuria. Vitamin D supplementation in doses of 400 IU/day is recommended during infancy; however, the estimated average requirement in older children and adolescents (400-600 IU/day, respectively) should be met from diet and natural sources like sunlight. Rickets and vitamin D deficiency should be treated with oral cholecalciferol, preferably in a daily dosing schedule (2000 IU below 1 year of age and 3000 IU in older children) for 12 weeks. If compliance to daily dosing cannot be ensured, intermittent regimens may be prescribed for children above 6 months of age. Universal vitamin D supplementation is not recommended in childhood pneumonia, diarrhea, tuberculosis, HIV and non-infectious conditions like asthma, atopic dermatitis, and developmental disorders. Serum 25-hydroxy vitamin D level of >20 ng/mL should be maintained in children with conditions at high-risk for vitamin deficiency, like nephrotic syndrome, chronic liver disease, chronic renal failure, and intake of anticonvulsants or glucocorticoids.

Occurrence of infections in schoolchildren subsequent to supplementation with vitamin D-calcium or zinc: a randomized, double-blind, placebo-controlled trial.

BACKGROUND/OBJECTIVES: Vitamin D and zinc are recognized for their roles in immune-modulation, and their deficiencies are suggested to be important risk factors for childhood infections. This study, therefore, undertook to assess the occurrence of infections in rural Indian schoolchildren, subsequent to daily supplementation with vitamin D-calcium or zinc for 6 months. MATERIALS/METHODS: This was a randomized, double-blind, placebo-controlled trial in apparently healthy 6-12 year-old rural Indian children, recruited to 3 study arms: vitamin D arm (1,000 IU D3 - 500 mg calcium, n = 135), zinc arm (10 mg, n = 150) and placebo arm (n = 150). The infection status was assessed using a validated questionnaire, and the biochemical parameters of serum 25(OH)D and serum zinc were measured by ELISA and colorimetry, respectively. The primary outcome variable was occurrence of infections (upper respiratory and total infections). RESULTS: Serum 25(OH)D concentration in the vitamin D arm improved significantly by 34%, from 59.7 ± 10.9 nmol/L to 80 ± 23.3 nmol/L (P < 0.0001), but no improvement was observed for serum zinc concentration. While there was significant increase in the percentage of children reporting no or mild upper respiratory tract infections (URTI) and total infections (TI) in all three groups, improvements in the supplemented groups were similar to the placebo group. However, the vitamin D arm reported lower URTI and TI status in the vitamin D sufficient versus insufficient children. Also, URTI and TI status were found to be significantly (P < 0.0001) lower in children with improved 25(OH)D versus unchanged 25(OH)D. CONCLUSIONS: Vitamin D-calcium supplementation helped to improve the vitamin D status but exerts no effect on the occurrence of infections when compared to the placebo group. Improvement in the serum 25(OH)D concentrations and attainment of vitamin D sufficiency may exert a beneficial effect on the infection status and needs to be investigated further. To evaluate the efficacy of zinc supplementation, higher dosages need to be administered in future studies.

Paradoxical Response of Parathyroid Hormone to Vitamin D-Calcium Supplementation in Indian Children.

OBJECTIVES: To investigate the effect of oral vitamin D-calcium supplementation on serum intact parathyroid hormone (PTH), calcium, phosphorous, and alkaline phosphatase (ALK-P) concentrations in children with habitually low calcium intakes. STUDY DESIGN: In this follow-up study to a randomized controlled trial that aimed to assess the effect of vitamin D-calcium supplementation on immunity, data related to dietary intake, anthropometry, and biochemistry [serum 25(OH)D and bone profile] were collected from 178 children-79 in the vitamin D group and 99 in the non-vitamin D group. RESULTS: Dietary calcium to phosphorus intake ratio was 0.4:1. Baseline serum 25(OH)D concentration was 58.2 ± 10.9 nmol/L; 66% children were vitamin D sufficient and none deficient. After supplementation, vitamin D group, compared with the non-vitamin D group, had significantly (P < .05) greater 25(OH)D (83.9 ± 30.1 nmol/L vs 58.3 ± 15.7 nmol/L), significantly greater PTH (6.7 ± 3.6 pmol/L vs 5.5 ± 3.2 pmol/L), and positive correlation (rs = 0.24) between serum 25(OH)D and PTH (vs negative correlation [rs = -0.1] in non-vitamin D group). Mean concentrations of serum bone measures in the vitamin D group were calcium (2.2 ± 0.1 mmol/L), phosphorus (1.7 ± 0.2 mmol/L), and ALK-P (178.7 ± 40.7 IU/L). At follow-up, 1-year post-supplementation, in the vitamin D group, PTH concentrations continued to remain high (but not significantly different from levels at 6 months), with low normal serum calcium, high normal phosphate, and ALK-P in reference range. CONCLUSIONS: In children who are vitamin D sufficient but with habitually low dietary calcium intake, vitamin D-calcium supplementation paradoxically and significantly increased serum PTH concentrations with no apparent effect on other bone biochemistry. Chronic low dietary calcium to phosphorus ratio is likely to have caused this paradoxical response.

Effect of Antioxidant Supplementation on Total Antioxidant Status in Indian Children with Type 1 Diabetes.

Hyperglycemia results in the overproduction of free oxygen radicals that impair the endogenous antioxidant defenses. A randomized controlled trial was conducted to compare the effect of 3 months of antioxidant supplementation in the form of foods rich in micronutrients with pharmacological supplement on total antioxidant status of Indian children with type 1 diabetes. Ninety children with diabetes (mean age 11.5 ± 3.6 yrs, 37 boys) were randomly allocated to three groups: Group 1 (n = 31) = DM controls; Group 2 (n = 30) = multimicronutrient syrup; and Group 3 (n = 29) = dietary supplements (nine snack recipes rich in micronutrients). They received intervention for 3 months. Healthy controls were enrolled from local schools. Fasting blood was tested for total antioxidant status (TAS) and glycosylated hemoglobin (HbA1C). Children with diabetes had lower TAS (0.70 ± 0.2 vs. 1 ± 0.24 mmol/l, p = .0001) compared to healthy controls. Anthropometric and biochemical parameters were similar at baseline for all groups of diabetic children. Group 1 showed significant deterioration in TAS at endline (0.72 ± 0.16 vs. 0.60 ± 0.17 mmol/l, p = .008). Increase in TAS recorded in Group 2 was from 0.66 ± 0.21 to 0.70 ± 0.16 mmol/l and in Group 3 was from 0.68 to 0.73 mmol/l. There was a significant difference between Group 1 and Group 3 for percentage change in TAS (-13% vs. 16%, p = .035). Postsupplementation there was an increase in TAS values in children with diabetes, but they were still lower than in healthy controls. Indian diabetic children have compromised antioxidant status, which may be improved by incorporation of multimicronutrient-rich recipes in their diets.

Response of serum 25(OH)D to Vitamin D and calcium supplementation in school-children from a semi-rural setting in India.

The objectives of this study were to: 1) Determine the impact of varying baseline serum 25OHD on increase in vitamin D concentrations after daily supplementation with vitamin D and calcium (1000 IU + 500 mg respectively) for six months in school-children from a semi-rural setting 2) Test the efficacy of daily vitamin D-calcium supplementation on improvement in serum vitamin D concentrations to ≥75 nmol/L. Data collected from 106 subjects (58 boys, 48 girls), aged 6-12 years, included anthropometric measures like height and weight, body composition analysis, three one-day dietary recalls and sunlight exposure (by questionnaire). Blood was collected at baseline and endline and estimated for serum vitamin D by ELISA technique using standard kits. Classification of Vitamin D status was performed according to the 2011 Endocrine Society Practice Guidelines: vitamin D deficiency - <50 nmol/L; insufficiency - 50.0-74.9 nmol/L; sufficiency - ≥75 nmol/L. Statistical analysis was performed using SPSS software. Mean baseline serum vitamin D concentration was 59.7 ±â€¯11.2 nmol/L; this rose to 79.8 ±â€¯23.3 nmol/L with no significant differences between genders at the two time-points. Inverse relationship was obtained between baseline serum 25(OH)D concentrations and change in serum concentrations after supplementation, implying that with increasing baseline serum concentrations of 25(OH)D, increase in vitamin D levels post supplementation were significantly lower (r = - 0.96, p < 0.0001). Greatest benefit of change in serum vitamin D concentrations after supplementation was experienced by children with basal concentrations of <45 nmol/L. Daily vitamin D supplementation was effective in improving serum 25(OH)D to ≥75 nmol/L in 44% of children. Significantly higher percentage of children who were deficient at baseline (64%) were able to attain serum concentrations of ≥75 nmol/L as compared to children who were vitamin D insufficient (43%) (p < 0.001). Thus, daily supplementation with 1000 IU of vitamin D along with 500 mg of calcium helped in improving serum vitamin D concentrations to ≥75 nmol/L. Children who were vitamin D deficient particularly experienced these benefits.

Randomized Control Trial Assessing Impact of Increased Sunlight Exposure versus Vitamin D Supplementation on Lipid Profile in Indian Vitamin D Deficient Men.

BACKGROUND: Despite abundance of sunshine in India, Vitamin D deficiency is common and therefore there is an increasing trend toward taking Vitamin D supplements either as prescription medicine or as a nutritional supplement. Studies have suggested that duration of sun exposure may influence serum lipid profile. OBJECTIVES: To study the effect of increased sunlight exposure versus Vitamin D supplementation on Vitamin D status and lipid profile in individuals with Vitamin D deficiency (25-hydroxyvitamin-D [25OHD] <50 nmol/L). DESIGN: A prospective, randomized open-label trial was carried out in apparently healthy Indian men (40-60 years). Based on 25OHD concentrations, individuals were divided into control (>50 nmol/L, n = 50) and intervention (<50 nmol/L, n = 100) groups. Individuals from intervention group were randomly allocated to two groups; either "increased sunlight exposure group" (n = 50, received at least 20 min sunlight exposure to forearms and face between 11 a.m. and 3 p.m. over and above their current exposure) or "cholecalciferol supplement group" (n = 50, received oral cholecalciferol 1000 IU/day). RESULTS: Significant increase in 25OHD concentrations was seen in both intervention groups (P < 0.01). Significant decrease in total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), and low-density-lipoprotein cholesterol (LDL-C) was seen in individuals with increased sunlight exposure (P < 0.05). Cholecalciferol supplement group showed a significant increase in TC and HDL-C (P < 0.05) and insignificant increase in LDL-C. CONCLUSIONS: Increase in Vitamin D concentrations through sunlight exposure significantly reduced TC, LDL-C, and HDL-C concentrations, and cholecalciferol supplementation increased TC and HDL-C concentrations.

A Cross-Sectional Study of Postpartum Changes in Bone Status in Indian Mothers.

BACKGROUND: Bone turnover is high during lactation. However, studies on bone status of Indian urban mothers are scarce. Hence, the objective was to conduct a cross-sectional study on the lactation-related changes in bone health status of Indian mothers postpartum using Dual X-ray Absorptiometry (DXA) at 3 time points: within a week of delivery, at 1- and 3-years postpartum. We also explored the association of dietary calcium intake, physical activity, serum vitamin D status, and dietary traditional food supplements (Dietary Food supplements) with bone health. METHODS: A cross-sectional study was conducted; 300 full-term, healthy primiparous women (28.6 ± 3.4 year) were randomly selected and categorized into 3 groups: 128 mothers within 7 days of delivery (Group A), 88 with 1-year-old children (B), and 84 with 3-year-old children (C). Anthropometry, lactation history, physical activity, diet, biochemical tests (vitamin D, parathyroid hormone), body composition, areal bone mineral density (a-BMD) at total body (TB), AP spine (APS), and dual neck femur (DF) were assessed by DXA (GE-Lunar DPX). RESULTS: Significantly higher APS-BMD (mean ± SD) was observed in Group C (1.107 ± 0.098 g/cm(2)) than that in A (1.045 ± 0.131 g/cm(2)) (p < 0.05). When adjusted for breastfeeding practices, mean (±standard error) APS-BMD was lowest in women in Group A (1.024 ± 0.013 g/cm(2)), but was higher at 1-year (1.079 ± 0.02 g/cm(2)) and at 3-years postpartum (1.111 ± 0.019 g/cm(2)), though differences were significant only between groups A and C (p < 0.05). Most mothers from all 3 groups consumed inadequate amount of nutrients except dietary fat and showed low physical activity. Multiple regression analysis indicated that dietary calcium, moderate physical activity, serum vitamin D, and consumption of dietary food supplements were not significant predictors of APS-BMD (p > 0.1). CONCLUSION: Prevalence of nutrient and vitamin D deficiencies, low physical activity, and poor sunlight exposure were major concerns in Indian lactating mothers; improvement in bone mass at APS was observed at 3-years which was most likely due to physiologic changes.

Changes in body composition of Indian lactating women: a longitudinal study.

BACKGROUND AND OBJECTIVES: Lactation places enormous demands on maternal bone mineral homeostasis. Indian middle class women (MSC) consume energy dense food supplements to meet these demands post-partum (PP) along with restricted physical activity (PA). Effects of these changes on body composition (BC) of PP women have not been studied. To examine longitudinal changes in: a) bone mineral density (BMD) at total body (TB), AP-spine (APS) and dual femur neck regions (DF) b) BC by body weight, lean mass, fat mass using dual energy X-ray absorptiometry (DXA) at baseline, 6-months and 1-year in urban MSC women. METHODS AND STUDY DESIGN: 76-primi-parous (28±3.2 yrs) randomly selected PP women (<7-days) were studied; 70 reassessed at 6- months and 42 1-yr PP. Data on anthropometry, BC, BMD at TB, APS and DF by DXA collected (baseline, 6- months, 1-yr PP). RESULTS: Weight, waist and body mass index (BMI) decreased both at 6-month and 1-yr PP with respect to baseline (p<0.05). BC changes showed increase in android fat % at 1-yr by 10% over baseline (p<0.05). BMD with initial decline at 6-months (-2.8%, -2.3% and -2.3% respectively) recovered partially by 1-yr (+2.5% +1.2% and +4.8% respectively) at DF and TB with complete recovery at APS (p<0.05). CONCLUSION: These urban relatively sedentary MSC women consumed fat rich food PP with higher android fat retention and partial recovery of BMD at DF and TB at 1-year. Modifications in activity and dietary nutrient intakes may be necessary to prevent cardiovascular and bone health related risks.

Influence of Vitamin D Receptor Gene Fok1 Polymorphism on Bone Mass Accrual Post Calcium and Vitamin D Supplementation.

OBJECTIVE: To examine the association of vitamin D receptor (VDR) gene polymorphisms of the Fok1 locus on bone mass accrual in Indian girls used to a low calcium intake. METHODS: An intervention trial was undertaken in 102 girls aged 8-16 y, attending a state run school in Pune city, India. All girls received 500 mg calcium daily and 30,000 IU of vitamin D3 quarterly for one year. Dietary calcium intake was evaluated. Bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) were measured at total body using Dual Energy X-ray Absorptiometry (Lunar DPX-PRO). Polymorphisms of the Fok1 locus of the vitamin D Receptor (VDR) gene were detected using SYBR Green quantitative polymerase chain reaction. RESULTS: The prevalence of Fok1 polymorphism was 43.1% (Ff), 9.8% (ff) and 47.1% (FF). At baseline, FF genotype had significantly lower BMD as compared to ff and Ff genotype (p < 0.05). At baseline, majority of girls (82.4%) were hypocalcemic with low calcium intake. Post-supplementation, FF genotype had significantly lower bone mass as compared to ff and Ff genotype. Significant increase in BMC [Ff (17.9%); ff (18.1%); FF (17.4%)], and BMD [Ff (5.4 %); ff (6.3%); FF (4.8%)] was observed post supplementation (p value < 0.05), though percentage increase in BMC and BMD was similar for three Fok1 polymorphisms (p > 0.1). CONCLUSIONS: VDR gene polymorphism, as defined by Fok1 genotype had no positive influence on bone mass accrual in response to calcium supplementation.

Effect of micronutrient supplementation on height velocity of underprivileged girls in comparison with un-supplemented healthy controls.

The aim of this study was to investigate the effect of 1-year micronutrient supplementation on the height velocity of underprivileged premenarchal girls in comparison with the natural growth of apparently healthy girls from an affluent class. A 1-year cluster-randomisation intervention trial was conducted in 119 premenarchal girls (8-12 years) from two schools catering to the lower socioeconomic strata (LSES) in Pune, India. Three classes of age-matched girls were randomly allocated to any one of the three intervention groups: (i) Ca+MZn+D group (C1: zinc, 15 mg/day+multivitamins; calcium, 500 mg/day; vitamin D, 30,000 IU/3 months); (ii) Ca+D group (C2: calcium, 500 mg/day; vitamin D, 30,000 IU/3 months); and (iii) M+D group (C3: multivitamins; vitamin D, 30,000 IU/3 months). Height, weight, and Tanner stage were assessed at baseline and endline. A total of 119 age-matched, apparently healthy school girls from a higher socioeconomic group (HSES) were assessed for their growth after 1 year without any supplementation. At baseline, mean height-for-age Z-scores and weight-for-age Z-scores by Indian references were >-2 in 99% of HSES girls and 28% of LSES girls had height-for-age Z-scores <-2. Post-intervention, increase in height-for-age Z-scores adjusted for Tanner stage was significantly higher in the Ca+MZn+D group (0.32±0.06) than in the respective age-matched controls (C1 group) (-0.02±0.05) (p<0.05) as well as in both the Ca+D group (0.18±0.06) and the M+D group (0.14±0.04) (p<0.05). After adjusting for Tanner stage, height velocity was significantly higher for the Ca+MZn+D group (6.7±0.4 cm/year) than for the M+D group (6.1±0.2), Ca+D group (5.6±0.5) as well as age-matched controls (C1 group) (5.0±0.3) (p<0.05). Supplementation with calcium+vitamin D, zinc and multivitamins may be effective in improving stature in underprivileged Indian premenarchal girls.

Use of vitamin D in various disorders.

Approximately 1 billion people worldwide have been identified as vitamin D deficient in the 21st century, and the number is on the rise; non-classical actions of vitamin D were initially recognized around 30 y ago when receptors for vitamin D were detected in neoplastic cells lines. The aim of this review is to provide a brief overview of the non-classical actions of vitamin D. Reports describing the associations of non skeletal actions of vitamin D, especially pertaining to the immune system, inflammatory disorders, cancers and cardiovascular disease have been summarized in this paper. Reports support a role for the active form of vitamin D in mediating normal function of both the innate and adaptive immune systems. Studies also suggest a link between vitamin D deficiency and autoimmune diseases, such as rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus and type 1 diabetes. There is believed to be an inverse association between serum 25-hydroxyvitamin D concentrations and the incidence of colorectal cancer, sporadic colorectal adenoma and breast cancer. Vitamin D deficiency has been linked with various cardiovascular diseases such as hypertension, myocardial infarction, and stroke. Several epidemiological and genetic studies suggest a strong association between vitamin D and non skeletal acute and chronic disorders. However, currently, robust clinical data are still lacking to support raising intake requirements and target vitamin D plasma levels. Nonetheless, the high prevalence of vitamin D deficiency is alarming and requires implementation of clear supplementation guidelines.

Enhanced effect of zinc and calcium supplementation on bone status in growth hormone-deficient children treated with growth hormone: a pilot randomized controlled trial.

Reduced bone mineral content in growth hormone-deficient children (GHD) has been reported. Calcium, zinc, and vitamin D play an important role in bone formation. Hence, the aim of this pilot randomized controlled study was to evaluate the effect of calcium, vitamin D, and zinc supplementation in prepubertal GHD children treated with GH on bone health parameters. After 1 year of treatment with GH (20 mg/m(2)/week), 31 GHD (mean age 8.7 ± 2.8 years, 18 boys) prepubertal children were randomised to receive calcium (500 mg/day) and vitamin D (60,000 IU/3 months) [Group A] or a similar supplement of calcium, vitamin D, and zinc (as per Indian Recommended Allowance) [Group B] along with GH therapy for the next 12 months. The two groups were similar in anthropometric and body composition parameters at baseline (p > 0.1). After 1 year of GH therapy, height-adjusted % gain was similar in both groups, 48 % in bone mineral content (BMC) and 45 % in bone area (BA). Height-adjusted % increase in BMC was significantly (p < 0.05) higher in the second year than in the first in both the groups. This % increase in BMC and BA was greater in Group B (51 and 36 % respectively) than in Group A (49 and 34 %), although marginally (p < 0.05). Supplementation of calcium and vitamin D along with GH therapy in GHD Indian children has the potential for enhancing bone mass accrual; this effect was further enhanced through the addition of zinc supplement.

Vitamin D receptor gene polymorphisms and bone mass indices in post-menarchal Indian adolescent girls.

To study the association between vitamin D receptor (VDR) gene polymorphisms and bone mass indices in adolescent girls, a cross-sectional study was conducted in 120 post-menarchal girls aged 15-18 years in Pune city, India. Serum levels of ionised calcium, inorganic phosphorous, parathyroid hormone and 25-hydroxy vitamin-D were measured. Bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) were measured at total body (TB), lumbar spine (LS) and left femoral neck (FN) using dual energy X-ray absorptiometry. Polymorphisms of the VDR gene at the Fok1 and Bsm1 loci were detected using SYBR Green quantitative polymerase chain reaction. The overall distribution of genotypes at the Bsm1 locus in this study was 33.3 % Bb, 29.2 % bb and 37.5 % BB while that for the Fok1 locus was 44.2 % Ff, 7.5 % ff and 48.3 % FF. There were no significant differences in the blood parameters when classified according to Bsm1 or Fok1 genotypes. Subjects with BB genotype have significantly higher mean TBBMC, TBBA, TBBMD and LSBMD than Bb and bb (p < 0.05) and showed a tendency for association with LSBMC and LSBA (p < 0.1). Subjects with Ff genotype showed a tendency for association with left FNBMC and FNBA (p < 0.1). Bsm1 genotype did not show an association with FN bone indices whereas Fok1 genotype did not show association with TB or LS bone indices. In conclusion, the present study demonstrates VDR gene polymorphism, defined by Bsm1 genotype, has an influence on total body and lumbar spine bone mass indices in post-menarchal Indian girls.

School-based calcium-vitamin D with micronutrient supplementation enhances bone mass in underprivileged Indian premenarchal girls.

Low adult bone mass is linked to osteoporosis and fractures and is dependent on the extent of childhood and adolescent bone mineralization. The aim of the study was to investigate the effect of 1-year supplementation of calcium, multivitamin with zinc along with vitamin-D on bone mass accrual of school-going premenarchal girls from low income groups in Pune, India. Double-blind, matched-pair, cluster, randomization study was carried out in 214 premenarchal girls (8-12 years) from 2 schools in Pune, India. The two schools together formed 3 classes with 3 clusters each of age-matched girls of which one cluster was allocated to either one of the intervention groups (Ca-group:500 mg/d calcium, Ca+MZ-group:500 mg/d calcium+multivitamin tablet containing 15 mg/d zinc) or control group (C-group: multivitamin tablet without any minerals); all subjects received vitamin-D supplementation. Anthropometry, biochemical parameters, total body bone mineral content (TBBMC) and bone mineral density (TBBMD) (Dual energy X-ray absorptiometry) were assessed at baseline and endline. Post supplementation, mean percent increase in TBBMC was significantly higher in Ca-group (22.3%) and Ca+MZ-group (20.8%) compared to C-group (17.6%) (p<0.05) with no significant differences observed between Ca+MZ and Ca groups (p>0.1). Improvement in TBBMC-for-age Z-scores was higher in the two calcium supplemented groups (13.6%-22%) compared to the C-group (no improvement). Calcium supplementation, with or without multivitamins and zinc, showed a promising improvement in bone health especially with regards to improvement in bone related Z-scores in our population of underprivileged premenarchal girls.

Invited commentary to the paper 'Zinc status and its association with the health of adolescents: a review of studies in India'.

We are pleased to view the article based on Dr. Rama Kawade's thesis illustrating the importance of micronutrient adequacy, especially zinc, and associated health implications in Indian adolescent girls. This brief commentary addresses three major aspects in which Kawade's work has made a significant contribution; nutrition and health issues of adolescents, rising importance of zinc in terms of deficiency problems being addressed, and development of dietary interventions to alleviate micronutrient deficiencies.

Diet and exercise intervention, with special reference to micronutrients, reduces cardiometabolic risk in overweight children.

OBJECTIVE: To study the effect of lifestyle intervention in the presence of multivitamin-zinc supplementation in improving the cardiometabolic status of overweight children. MATERIALS AND METHODS: Data were evaluated in 74 overweight children (11.3 ± 2.9 years) randomly assigned to three groups of intervention for 4 months as follows: group A: diet-exercise counseling with multivitamin-zinc supplementation; group B: diet-exercise counseling; and group C: placebo. Anthropometric, biochemical, carotid arterial and lifestyle parameters were assessed. RESULTS: Lifestyle counseling resulted in significant reduction in inactivity, energy and fat intakes and increase in micronutrient density of diets and physical activity in groups A and B in comparison to group C. Percent decline in body fat was more in group A than in groups B and C. Percent change in triglycerides (-13.7%) was significantly higher in group A than in groups B (-5.9%) and C (5.7%). Pulse wave velocity and elasticity modulus reduced and arterial compliance improved significantly in group A than in group B. CONCLUSION: Multivitamin-zinc supplementation with lifestyle intervention has a positive effect of on the cardiometabolic status of overweight children.