Joyce Maalouf

Short- and Long-Term Safety of Weekly High-Dose Vitamin D3 Supplementation in School Children

BACKGROUND Hypovitaminosis D is prevalent in youth worldwide, but the safety of vitamin D at doses exceeding 200 IU/d is unknown in this age group. We assessed the safety of high doses of vitamin D(3) administered to apparently healthy schoolchildren. METHODS To assess short-term safety, 25 subjects randomly received placebo or vitamin D(3) at doses of 14,000 IU/wk for 8 wk. To assess long-term safety, 340 subjects randomly received placebo, vitamin D(3) as 1,400 IU/wk or 14,000 IU/wk for 1 yr. Biochemical variables were monitored at 0, 2, 4, 6, and 8 wk and 8 wk off therapy in the short-term study and at 0, 6, and 12 months in the long-term study. RESULTS In both the short- and long-term studies, mean serum calcium and 1,25-hydroxyvitamin levels did not change in any group. In the short-term study, mean 25-hydroxyvitamin concentrations increased from 44 (+/- 11) to 54 (+/- 19) ng/ml in the treated groups (P = 0.033). In the long-term study, mean 25-hydroxyvitamin D levels increased from 15 +/- 8 to 19 +/- 7 ng/ml (P < 0.0001) in subjects receiving 1,400 IU/wk and from 15 +/- 7 to 36 +/- 22 ng/ml (P < 0.0001) in the group receiving 14,000 IU/wk. No subject developed vitamin D intoxication. CONCLUSION Vitamin D(3) at doses equivalent to 2000 IU/d for 1 yr is safe in adolescents and results in desirable vitamin D levels.

Vitamin D receptor gene polymorphisms modulate the skeletal response to vitamin D supplementation in healthy girls

OBJECTIVES Vitamin D receptor (VDR) gene plays an important role in bone mass regulation. We have previously shown a beneficial effect of vitamin D supplementation on bone mass in girls. This study investigated whether the musculo-skeletal response to Vitamin D was modulated by polymorphisms in VDR gene. DESIGN Randomized placebo-controlled trial. METHODS 179 girls (10-17 years), were randomly assigned to placebo or Vitamin D3 for one year. VDR genotypes were determined in 167 girls using BsmI, TaqI and ApaI restriction enzymes. Bone mass at the spine, hip, forearm and total body, and lean mass were measured by DXA at baseline and at one year. RESULTS After one year, VDR gene polymorphisms using Bsm1 and TaqI restriction enzymes were associated with percent changes in bone area, BMC and BMD at multiple skeletal sites in the Vitamin D3 group but not in the placebo group. The least increments were observed in the BB and tt genotypes. No similar effect was observed with ApaI enzyme. This relationship between VDR genotypes and changes in BMD and BMC remained significant after adjustment for puberty, changes in lean mass, height and bone area. CONCLUSION VDR gene polymorphisms influence the skeletal response to vitamin D supplementation in healthy adolescent girls.

Impact of maternal veiling during pregnancy and socioeconomic status on offspring’s musculoskeletal health

SummaryThe impact of maternal veiling during pregnancy and of socioeconomic status on offspring’s bone mass was investigated in 326 healthy adolescents. Veiling during pregnancy was associated with decreased musculoskeletal parameters in the offspring boys, but not girls. SES was a significant predictor of bone mass in both genders.IntroductionThis study investigates the effects of maternal veiling during pregnancy, a surrogate for low vitamin D level, and socioeconomic status (SES), a surrogate of nutritional status, on their offspring’s bone mass at adolescence.MethodsThree hundred and twenty-six healthy adolescents aged 13.1(2.0) years and their mothers were studied. The impact of maternal veiling on offspring’s bone mass was evaluated through regression analyses. Outcome variables were bone mineral density (BMD) and content (BMC) at the spine, hip, and total body of the children. Predictors were maternal veiling during pregnancy and SES. Covariates were height, body composition, Tanner staging, calcium intake, vitamin D and exercise in children.ResultsIn boys, adjusted analyses revealed that both maternal veiling during pregnancy and SES were significant predictors of bone mass, at multiple skeletal sites. In girls, SES but not maternal veiling during pregnancy was a significant predictor of bone mass at multiple sites.ConclusionMaternal veiling during pregnancy was associated with decreased musculoskeletal parameters of boys, but not girls. SES was a significant predictor of bone mass in both genders. These findings may have profound implications on children’s bone health.

Vitamin D3 dose requirement to raise 25-hydroxyvitamin D to desirable levels in adolescents: results from a randomized controlled trial.

Several organizations issued recommendations on desirable serum 25‐hydroxy vitamin D [25(OH)D] levels and doses of vitamin D needed to achieve them. Trials allowing the formulation of evidence‐based recommendations in adolescents are scarce. We investigated the ability of two doses of vitamin D3 in achieving recommended vitamin D levels in this age group. Post hoc analyses on data from a 1‐year double‐blind trial that randomized 336 Lebanese adolescents, aged 13 ± 2 years, to placebo, vitamin D3 at 200 IU/day (low dose), or 2000 IU/day (high dose). Serum 25(OH)D level and proportions of children achieving levels ≥20 ng/mL and 30 ng/mL were determined. At baseline, mean 25(OH)D was 15 ± 7 ng/mL, 16.4 ± 7 ng/mL in boys, and 14 ± 8 ng/mL in girls, p = 0.003, with a level ≥20 ng/mL in 18% and ≥30 ng/mL in 5% of subjects. At 1 year, mean levels were 18.6 ± 6.6 ng/mL in the low‐dose group, 17.1 ± 6 ng/mL in girls, and 20.2 ± 7 ng/mL in boys, p = 0.01, and 36.3 ± 22.3 ng/mL in the high‐dose group, with no sex differences. 25(OH)D increased to ≥20 ng/mL in 34% of children in the low‐dose and 96% in the high‐dose group, being higher in boys in the low‐dose arm only; it remained ≥30 ng/mL in 4% of children in the low‐dose arm but increased to 64% in the high‐dose arm. Baseline 25(OH)D level, body mass index (BMI), and vitamin D dose assigned were the most significant predictors for reaching a 25(OH)D level ≥20 ng/mL and 30 ng/mL. A daily dose of 2000 IU raised 25(OH)D level ≥20 ng/mL in 96% of adolescents (98% boys versus 93% girls). Dose‐response studies are needed to determine in a definitive manner the daily allowance of vitamin D for Middle Eastern adolescents with a similar profile.

Effect of vitamin D replacement on hip structural geometry in adolescents: A randomized controlled trial

BACKGROUND We have shown in a randomized controlled trial that vitamin D increases bone mass, lean mass and bone area in adolescent girls, but not boys. These increments may translate into improvements in bone geometry and therefore bone strength. This study investigated the impact of vitamin D on hip geometric dimensions from DXA-derived hip structural analyses in adolescents who participated in the trial. METHODS 167 girls (mean age 13.1 years) and 171 boys (mean age 12.7 years) were randomly assigned to receive weekly placebo oil or vitamin D3, at doses of 1400 IU or 14,000 IU, in a double blind placebo-controlled 1-year trial. DXA images were obtained at baseline and one year, and hip images were analyzed using the hip structural analysis (HSA) software to derive parameters of bone geometry. These include outer diameter (OD), cross sectional area (CSA), section modulus (Z), and buckling ratio (BR) at the narrow neck (NN), intertrochanteric (IT), and shaft (S) regions. Analysis of Covariance (ANCOVA) was used to examine group differences for changes of bone structural parameters. RESULTS In the overall group of girls, vitamin D supplementation increased aBMD (7.9% and 6.8% in low and high doses, versus 4.2% in placebo) and reduced the BR of NN (6.1% and 2.4% in low and high doses, versus 1.9% in placebo). It also improved aBMD (7.9% and 5.2% versus 3.6%) and CSA (7.5% and 5.1% versus 4.1%) of the IT and OD of the S (2.4% and 2.5% versus 0.8% respectively). Significant changes in the OD and BR of the NN, in the overall group of girls remained, after adjusting for lean mass, and were unaffected with further adjustments for lifestyle, pubertal status, and height measures. Conversely, boys did not exhibit any significant changes in any parameters of interest. A dose effect was not detected and subgroup analyses revealed no beneficial effect of vitamin D by pubertal stage. CONCLUSIONS Vitamin D supplementation improved bone mass and several DXA-derived structural bone parameters, in adolescent girls, but not boys. This occurred at a critical site, the femoral neck, and if maintained through adulthood could improve bone strength and lower the risk of hip fractures.

Vitamin D3 dose requirement to raise 25-hydroxyvitamin D to desirable levels in adolescents: Results from a randomized controlled trial

Several organizations issued recommendations on desirable serum 25‐hydroxy vitamin D [25(OH)D] levels and doses of vitamin D needed to achieve them. Trials allowing the formulation of evidence‐based recommendations in adolescents are scarce. We investigated the ability of two doses of vitamin D3 in achieving recommended vitamin D levels in this age group. Post hoc analyses on data from a 1‐year double‐blind trial that randomized 336 Lebanese adolescents, aged 13 ± 2 years, to placebo, vitamin D3 at 200 IU/day (low dose), or 2000 IU/day (high dose). Serum 25(OH)D level and proportions of children achieving levels ≥20 ng/mL and 30 ng/mL were determined. At baseline, mean 25(OH)D was 15 ± 7 ng/mL, 16.4 ± 7 ng/mL in boys, and 14 ± 8 ng/mL in girls, p = 0.003, with a level ≥20 ng/mL in 18% and ≥30 ng/mL in 5% of subjects. At 1 year, mean levels were 18.6 ± 6.6 ng/mL in the low‐dose group, 17.1 ± 6 ng/mL in girls, and 20.2 ± 7 ng/mL in boys, p = 0.01, and 36.3 ± 22.3 ng/mL in the high‐dose group, with no sex differences. 25(OH)D increased to ≥20 ng/mL in 34% of children in the low‐dose and 96% in the high‐dose group, being higher in boys in the low‐dose arm only; it remained ≥30 ng/mL in 4% of children in the low‐dose arm but increased to 64% in the high‐dose arm. Baseline 25(OH)D level, body mass index (BMI), and vitamin D dose assigned were the most significant predictors for reaching a 25(OH)D level ≥20 ng/mL and 30 ng/mL. A daily dose of 2000 IU raised 25(OH)D level ≥20 ng/mL in 96% of adolescents (98% boys versus 93% girls). Dose‐response studies are needed to determine in a definitive manner the daily allowance of vitamin D for Middle Eastern adolescents with a similar profile.

Top sources of dietary sodium from birth to age 24 mo, United States, 2003–2010

BACKGROUND Sodium intake is high in US children. Data are limited on the dietary sources of sodium, especially from birth to age 24 mo. OBJECTIVE We identified top sources of dietary sodium in US children from birth to age 24 mo. DESIGN Data from the NHANES 2003-2010 were used to examine food sources of sodium (population proportions and mean intakes) in 778 participants aged 0-5.9 mo, 914 participants aged 6-11.9 mo, and 1219 participants aged 12-23.9 mo by sociodemographic characteristics. RESULTS Overall, mean dietary sodium intake was low in 0-5.9-mo-old children, and the top contributors were formula (71.7%), human milk (22.9%), and commercial baby foods (2.2%). In infants aged 6-11.9 mo, the top 5 contributors were formula (26.7%), commercial baby foods (8.8%), soups (6.1%), pasta mixed dishes (4.0%), and human milk (3.9%). In children aged 12-23.9 mo, the top contributors were milk (12.2%), soups (5.4%), cheese (5.2%), pasta mixed dishes (5.1%), and frankfurters and sausages (4.6%). Despite significant variation in top food categories across racial/ethnic groups, commercial baby foods were a top food contributor in children aged 6-11.9 mo, and frankfurters and sausages were a top food contributor in children aged 12-23.9 mo. The top 5 food categories that contributed to sodium intake also differed by sex. Most of the sodium consumed (83-90%) came from store foods (e.g., from the supermarket). In children aged 12-23.9 mo, 9% of sodium consumed came from restaurant foods, and 4% of sodium came from childcare center foods. CONCLUSIONS The vast majority of sodium consumed comes from foods other than infant formula or human milk after the age of 6 mo. Although the majority of sodium intake was from store foods, after age 12 mo, restaurant foods contribute significantly to intake. Reducing the sodium content in these settings would reduce sodium intake in the youngest consumers.

Persistent Effect of Vitamin D Supplementation on Musculoskeletal Parameters in Adolescents One Year After Trial Completion.

We showed a beneficial effect of vitamin D supplementation on musculoskeletal parameters in adolescent girls in a 1‐year, randomized, double‐blinded placebo‐controlled trial (RCT). Our objective for this study was to investigate the residual effect of vitamin D supplementation on bone mineral content (BMC), bone mineral density (BMD), at the lumbar spine and hip, lean mass, and height, 1 year after trial completion. We performed post hoc analyses in 167 adolescents, 86 girls and 81 boys, age 13.9 ± 2 years, who received vitamin D or placebo during the trial, and continued into the follow‐up trial. Musculoskeletal parameters were measured at baseline, 12 months (intervention), and 24 months (follow‐up). ANOVA and t tests were used to compare results between the placebo group and the merged vitamin D arms (200 or 2000 IU/day), by gender. Baseline characteristics were comparable between treatment groups at entry into the extension. Girls who had received vitamin D during the trial, had significantly larger hip BMC increments compared to those assigned to placebo, at 24 months compared to study entry, but not 24 compared to 12 months, which persisted in adjusted analyses. There were no significant differences in bone mass changes between treatment groups in boys, at 24 months compared to 12 months or to baseline. The beneficial effect of vitamin D supplementation on hip bone mass, achieved in girls during the trial, persisted 1 year after trial completion. These net cumulative increments, 1 year after discontinuation of supplementation, may have important implications on optimizing peak bone mass accretion in adolescent girls.

Do Lower Calorie or Lower Fat Foods Have More Sodium Than Their Regular Counterparts

The objective of this study was to compare the sodium content of a regular food and its lower calorie/fat counterpart. Four food categories, among the top 20 contributing the most sodium to the US diet, met the criteria of having the most matches between regular foods and their lower calorie/fat counterparts. A protocol was used to search websites to create a list of “matches”, a regular and comparable lower calorie/fat food(s) under each brand. Nutrient information was recorded and analyzed for matches. In total, 283 matches were identified across four food categories: savory snacks (N = 44), cheese (N = 105), salad dressings (N = 90), and soups (N = 44). As expected, foods modified from their regular versions had significantly reduced average fat (total fat and saturated fat) and caloric profiles. Mean sodium content among modified salad dressings and cheeses was on average 8%–12% higher, while sodium content did not change with modification of savory snacks. Modified soups had significantly lower mean sodium content than their regular versions (28%–38%). Consumers trying to maintain a healthy diet should consider that sodium content may vary in foods modified to be lower in calories/fat.

Sodium content in packaged foods by census division in the United States, 2009.

Excess sodium intake correlates positively with high blood pressure. Blood pressure varies by region, but whether sodium content of foods sold varies across regions is unknown. We combined nutrition and sales data from 2009 to assess the regional variation of sodium in packaged food products sold in 3 of the 9 US census divisions. Although sodium density and concentration differed little by region, fewer than half of selected food products met Food and Drug Administration sodium-per-serving conditions for labeling as “healthy.” Regional differences in hypertension were not reflected in differences in the sodium content of packaged foods from grocery stores.