Lower dietary intake of magnesium is associated with more callous-unemotional traits in children.

BACKGROUND: Although researchers increasingly recognize the role of nutrition in mental health, little research has examined specific micronutrient intake in relation to antisocial behavior and callous-unemotional (CU) traits in children. Vitamin B6 and magnesium are involved in neurochemical processes implicated in modulating antisocial behavior and CU traits. The current study examined dietary intakes of magnesium and vitamin B6 in relation to antisocial behavior and CU traits. METHOD: : We enrolled 11-12 year old children (n = 446, mean age = 11.9 years) participating in the Healthy Brains and Behavior Study. Magnesium and vitamin B6 dietary intake were assessed with three 24-hour dietary recall interviews in children. CU traits and antisocial behavior were assessed by caregiver-reported questionnaires. We controlled for age, sex, race, total energy intake, body mass index, social adversity, ADHD or learning disability diagnosis, and internalizing behavior in all regression analyses. RESULTS: Children with lower magnesium intake had higher levels of CU traits, controlling for covariates (ß = -0.18, B = -0.0066, SE = 0.0027, p < 0.05). Vitamin B6 intake was not significantly associated with CU traits (ß = 0.061, B = 0.19, SE = 0.20, p > 0.05). Neither magnesium (ß = 0.014, B = 0.0020, SE = 0.0093, p > 0.05) nor vitamin B6 (ß = 0.025, B = 0.33, SE = 0.70, p > 0.05) were significantly associated with antisocial behavior. CONCLUSIONS: Findings suggest that low dietary intake of magnesium may play a role in the etiology of CU traits but not general antisocial behavior. More studies are needed to determine if magnesium supplementation or diets higher in magnesium could improve CU traits in children.

Stress gets into the belly: Early life stress and the gut microbiome.

Research has established that stress "gets under the skin," impacting neuroendocrine and neuroimmune pathways to influence risk for physical and mental health outcomes. These effects can be particularly significant for early life stress (ELS), or adverse childhood experiences (ACEs). In this review, we explore whether stress gets "into the belly," that is, whether psychosocial stress affects the gut microbiome. We review animal and human research utilizing a variety of stress paradigms (acute laboratory stressors, chronic stress, stressful life events, perceived stress, ELS, in utero stress) and their impacts on the gut microbiota, with a particular focus on ELS. We also review data on dietary interventions to moderate impact of stress on the gut microbiome. Our review suggests strong evidence that acute laboratory stress, chronic stress, and ELS affect the gut microbiota in rodents, and growing evidence that perceived stress and ELS may impact the gut microbiota in humans. Emerging data also suggests, particularly in rodents, that dietary interventions such as omega-3 fatty acids and pre- and pro-biotics may buffer against the effects of stress on the gut microbiome, but more research is needed. In sum, growing evidence suggests that stress impacts not only the neuroendocrine and neuroimmune axes, but also the microbiota-gut-brain-axis, providing a pathway by which stress may get "into the belly" to influence health risk.

Reproductive Hormone Concentrations and Associated Anatomical Responses: Does Soy Formula Affect Minipuberty in Boys?

CONTEXT: Soy formula feeding is common in infancy and is a source of high exposure to phytoestrogens, documented to influence vaginal cytology in female infants. Its influence on minipuberty in males has not been established. OBJECTIVE: To assess the association between infant feeding practice and longitudinally measured reproductive hormones and hormone-responsive tissues in infant boys. METHODS: The Infant Feeding and Early Development study was a prospective cohort of maternal-infant dyads requiring exclusive soy formula, cow milk formula, or breast milk feeding during study follow-up. In the 147 infant boy participants, serum testosterone, luteinizing hormone, stretched penile length, anogenital distance, and testis volume were longitudinally assessed from birth to 28 weeks. We examined feeding-group differences in age trajectories for these outcomes using mixed-effects regression splines. RESULTS: Median serum testosterone was at pubertal levels at 2 weeks (176 ng/dL [quartiles: 124, 232]) and remained in this range until 12 weeks in all feeding groups. We did not observe differences in trajectories of hormone concentrations or anatomical measures between boys fed soy formula (n = 55) and boys fed cow milk formula (n = 54). Compared with breastfed boys (n = 38), soy formula-fed boys had a more rapid increase in penile length (P = .004) and slower initial lengthening of anogenital distance (P = .03), but no differences in hormone trajectories. CONCLUSION: Reproductive hormone concentrations and anatomical responses followed similar trajectories in soy and cow milk formula-fed infant boys. Our findings suggest that these measures of early male reproductive development do not respond to phytoestrogen exposure during infancy.

Vitamin D3 supplementation in obese, African-American, vitamin D deficient adolescents.

OBJECTIVES: Obese, African-American (AA) adolescents are at increased risk for vitamin D deficiency. The primary objective of this pilot study was to examine the effect of vitamin D supplementation upon 25-hydroxy vitamin D (25OHD) levels in obese, AA adolescents. METHODS: A randomized, double-blinded, controlled pilot study included 26 obese (BMI ≥ 95%ile), vitamin D deficient (25OHD < 20 ng/mL), pubertal AA adolescents (ages 12-17). Subjects received cholecalciferol 1000 IU or 5000 IU daily for 3 months. Serum 25OHD, vitamin D binding protein, parathyroid hormone, and cardiometabolic risk markers were obtained at baseline and post-treatment. RESULTS: Of 39 subjects enrolled, 26 (67%) were vitamin D deficient (mean 25OHD 12.0 ±â€¯3.8 ng/mL) at baseline and were randomized, with 22 completing the study. Sex, age, season, pubertal stage, BMI, insulin resistance (HOMA-IR) and 25OHD were similar at baseline between the 1000 IU and 5000 IU groups. Post-treatment, 25OHD increased less in the 1000 IU group (5.6 ng/mL, p = 0.03) vs. the 5000 IU group (15.6 ng/mL, p = 0.002). 83% of the 5000 IU group and 30% of the 1000 IU group reached post-treatment 25OHD ≥ 20 ng/mL (p = 0.01); 50% of the 5000 IU group, but no subject from the 1000 IU group, achieved 25OHD ≥ 30 ng/mL (p = 0.009). We detected no group differences in mineral metabolites or cardiometabolic risk markers following supplementation. CONCLUSIONS: Cholecalciferol dosing in excess of the current Institute of Medicine dietary reference intakes was required to achieve 25OHD levels ≥20 ng/mL in obese, AA adolescents. Supplementation of 5000 IU may be required to achieve the desired goal.

A Longitudinal Study of Estrogen-Responsive Tissues and Hormone Concentrations in Infants Fed Soy Formula.

Purpose: Chemicals with hormonelike activity, such as estrogenic isoflavones, may perturb human development. Infants exclusively fed soy-based formula are highly exposed to isoflavones, but their physiologic responses remain uncharacterized. Estrogen-responsive postnatal development was compared in infants exclusively fed soy formula, cow-milk formula, and breast milk. Methods: We enrolled 410 infants born in Philadelphia-area hospitals between 2010 and 2014; 283 were exclusively fed soy formula (n = 102), cow-milk formula (n = 111), or breast milk (n = 70) throughout the study (birth to 28 or 36 weeks for boys and girls, respectively). We repeatedly measured maturation index (MI) in vaginal and urethral epithelial cells using standard cytological methods, uterine volume and breast-bud diameter using ultrasound, and serum estradiol and follicle-stimulating hormone levels. We estimated MI, organ-growth, and hormone trajectories by diet using mixed-effects regression splines. Results: Maternal demographics did not differ between cow-milk-fed and soy-fed infants but did differ between formula-fed and breastfed infants. Vaginal-cell MI trended higher (P = 0.01) and uterine volume decreased more slowly (P = 0.01) in soy-fed girls compared with cow-milk-fed girls; however, their trajectories of breast-bud diameter and hormone concentrations did not differ. We observed no significant differences between boys fed cow-milk vs soy formula; estradiol was not detectable. Breastfed infants differed from soy-formula-fed infants in vaginal-cell MI, uterine volume, and girls' estradiol and boys' breast-bud diameter trajectories. Conclusions: Relative to girls fed cow-milk formula, those fed soy formula demonstrated tissue- and organ-level developmental trajectories consistent with response to exogenous estrogen exposure. Studies are needed to further evaluate the effects of soy on child development.

Dose-response Effects of Aerobic Exercise Among Colon Cancer Survivors: A Randomized Phase II Trial.

BACKGROUND: Observational studies suggest that higher volumes of physical activity are associated with a lower risk of disease recurrence among survivors of colon cancer. However, the feasibility and safety of prescribing higher volumes of physical activity to survivors of colon cancer are unknown. Furthermore, the pathways through which exercise may reduce disease recurrence are unknown. PATIENTS AND METHODS: Survivors of stage I to III colon cancer were randomized to usual-care control, 150 minutes per week of aerobic exercise (low-dose), or 300 minutes per week of aerobic exercise (high-dose). Changes in soluble intercellular adhesion molecule-1 and vascular adhesion molecule-1 prognostic biomarkers were examined. RESULTS: From January 2015 to February 2016, 39 patients were enrolled (n = 13 usual-care control; n = 14 low-dose; n = 12 high-dose), and 38 participants completed the study (97% follow-up). Over 6 months, the low-dose group completed 142 minutes per week (92.8% adherence), and the high-dose group completed 247 minutes per week (89.0% adherence) of exercise. Compared with the control group, changes in soluble intercellular adhesion molecule-1 were -134.9 ng/mL (95% confidence interval, -238.1 to -31.6 ng/mL) in the low-dose group and -114.8 ng/mL (95% confidence interval, -222.5 to -7.1 ng/mL) in the high-dose group (linear Ptrend = .023; nonlinear Ptrend = .044). No changes were observed for soluable vascular adhesion molecule-1 (linear Ptrend = .791; nonlinear Ptrend = .604). Non-serious adverse events occurred at similar rates among randomized groups. No serious adverse events occurred. CONCLUSION: Higher volumes of moderate-intensity aerobic exercise, up to 300 minutes per week, are feasible, safe, and elicit favorable changes in prognostic biomarkers among patients recently treated for stage I to III colon cancer. These data can be used to guide clinical recommendations for patients, and inform future trials.

Comprehensive Safety Monitoring of 12-Month Daily 7000-IU Vitamin D3 Supplementation in Human Immunodeficiency Virus-Infected Children and Young Adults.

BACKGROUND: There is uncertainty whether long-term daily dosing with vitamin D3 (cholecalciferol) supplementation (vitD3) above the 4000-IU/d dietary reference intake upper tolerable limit in children and adults is safe. As part of a randomized placebo-controlled trial, we determined if supplementation with 7000-IU/d vitD3 for 12 months in human immunodeficiency virus (HIV)-Infected subjects was safe and/or associated with metabolic outcomes. MATERIAL AND METHODS: A total of 58 HIV-infected subjects-aged 9-24.9 years and stratified by mode of HIV acquisition (perinatal or behavioral)-were recruited, randomized to 7000-IU/d vitD3 or placebo, and followed at 3, 6, and 12 months with physical examinations, blood and urine sampling for measures of 25(OH)D (serum 25-hydroxyvitamin D), metabolic status, safety measures, and HIV immune status. Safety was defined by a low incidence (<5%) of the study-defined serious adverse events-that is, elevated serum calcium plus 25(OH)D >160 ng/mL-and no changes in hematologic, liver, renal, metabolic, lipid, or inflammatory status. RESULTS: Randomization groups did not differ in demographic characteristics, vitamin D status, or HIV disease status at baseline. Over the 12 months, serum 25(OH)D increased with supplementation. No subject experienced a serious adverse safety event; none had 25(OH)D >80 ng/mL at any time. There were no clinically significant changes in hematologic, liver, renal, metabolic, lipid, or inflammatory status. CONCLUSIONS: Safety of daily 7000-IU vitD3 supplementation in children and young adults with HIV was comprehensively monitored over 12 months. High-dose daily vitD3 supplementation was efficacious in improving vitamin D status, and there were no safety events.

Behavioral and nutritional treatment for preschool-aged children with cystic fibrosis: a randomized clinical trial.

IMPORTANCE: Evidence-based treatments that achieve optimal energy intake and improve growth in preschool-aged children with cystic fibrosis (CF) are a critical need. OBJECTIVE: To test whether behavioral and nutritional treatment (intervention) was superior to an education and attention control treatment in increasing energy intake, weight z (WAZ) score, and height z (HAZ) score. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial included 78 children aged 2 to 6 years (mean age, 3.8 years) with CF and pancreatic insufficiency (intervention, n = 36 and control, n = 42). The study was conducted at 7 CF centers between January 2006 and November 2012; all 78 participants who met intent-to-treat criteria completed through follow-up. INTERVENTIONS: Behavioral intervention combined individualized nutritional counseling targeting increased energy intake and training in behavioral child management skills. The control arm provided education and served as a behavioral placebo controlling for attention and contact frequency. Both treatments were delivered in person or telehealth (via telephone). Sessions occurred weekly for 8 weeks then monthly for 4 months (6 months). Participants then returned to standard care for 1 year, with 12-month follow-up thereafter. MAIN OUTCOMES AND MEASURES: Changes in energy intake and WAZ score were examined from pretreatment to posttreatment (6 months) and change in HAZ score was assessed pretreatment to follow-up (18 months). Covariates included sex, Pseudomonas aeruginosa status at baseline, and treatment modality (in person vs telehealth). RESULTS: At baseline, mean (SD) energy intake was 1462 (329) kcals/d, WAZ score was -0.44 (0.81), and HAZ score was -0.55 (0.84). From pretreatment to posttreatment, the intervention increased daily energy intake by 485 calories vs 58 calories for the control group (adjusted difference, 431 calories; 95% CI, 282 to 581; P < .001) and increased the WAZ score by 0.12 units vs 0.06 for the control (adjusted difference, 0.09; 95% CI, -0.06 to 0.24; P = .25). From pretreatment to follow-up, the intervention increased the HAZ score by 0.09 units vs -0.02 for the control (adjusted difference, 0.14 units; 95% CI, 0.001 to 0.27; P = .049). Measured treatment integrity and credibility were high for both groups. CONCLUSIONS AND RELEVANCE: Behavioral and nutritional intervention improved energy intake and HAZ score outcomes but not WAZ score outcomes. Our results provide evidence that behavioral and nutritional treatment may be efficacious as a nutritional intervention for preschoolers aged 2 to 6 years with CF and pancreatic insufficiency. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00241969.

Vitamin D3supplementation in Batswana children and adults with HIV: a pilot double blind randomized controlled trial.

OBJECTIVES: Since vitamin D insufficiency is common worldwide in people with HIV, we explored safety and efficacy of high dose cholecalciferol (D3) in Botswana, and evaluated potential modifiers of serum 25 hydroxy vitamin D change (Δ25D). DESIGN: Prospective randomized double-blind 12-week pilot trial of subjects ages 5.0-50.9 years. METHODS: Sixty subjects randomized within five age groups to either 4000 or 7000 IU per day of D3 and evaluated for vitamin D, parathyroid hormone, HIV, safety and growth status. Efficacy was defined as serum 25 hydroxy vitamin D (25D) ≥32 ng/mL, and safety as no simultaneous elevation of serum calcium and 25D. Also assessed were HIV plasma viral RNA viral load (VL), CD4%, anti-retroviral therapy (ART) regime, and height-adjusted (HAZ), weight-adjusted (WAZ) and Body Mass Index (BMIZ) Z scores. RESULTS: Subjects were 50% male, age (mean±SD) 19.5±11.8 years, CD4% 31.8±10.4, with baseline VL log10 range of <1.4 to 3.8 and VL detectable (>1.4) in 22%. From baseline to 12 weeks, 25D increased from 36±9 ng/ml to 56±18 ng/ml (p<0.0001) and 68% and 90% had 25D ≥32 ng/ml, respectively (p = 0.02). Δ25D was similar by dose. No subjects had simultaneously increased serum calcium and 25D. WAZ and BMIZ improved by 12 weeks (p<0.04). HAZ and CD4% increased and VL decreased in the 7000 IU/d group (p<0.04). Younger (5-13y) and older (30-50y) subjects had greater Δ25D than those 14-29y (26±17 and 28±12 vs. 11±11 ng/ml, respectively, p≤0.001). Δ25D was higher with efavirenz or nevirapine compared to protease inhibitor based treatment (22±12, 27±17, vs. 13±10, respectively, p≤0.03). CONCLUSIONS: In a pilot study in Botswana, 12-week high dose D3 supplementation was safe and improved vitamin D, growth and HIV status; age and ART regimen were significant effect modifiers. TRIAL REGISTRATION: ClinicalTrials.gov NCT02189902.

Vitamin D supplementation and antibacterial immune responses in adolescents and young adults with HIV/AIDS.

Human monocytes activated by toll-like receptor 2/1 ligand (TLR2/1L) show enhanced expression of the vitamin D receptor (VDR) and the vitamin D-activating enzyme 1α-hydroxylase (CYP27B1). The resulting intracrine conversion of precursor 25-hydroxyvitamin D3 (25OHD) to active 1,25-dihydroxyvitamin D (1,25(OH)2D) can stimulate expression of antibacterial cathelicidin (CAMP). To determine whether this response is functional in HIV-infected subjects (HIV+ ), serum from HIV+ subjects pre- and post-vitamin D supplementation was utilized in monocyte cultures with or without TLR2/1L. Expression of CYP27B1 and VDR was enhanced following treatment with TLR2/1L, although this effect was lower in HIV+ vs HIV- serum (p<0.05). CAMP was also lower in TLR2/1L-treated monocytes cultured in HIV+ serum (p<0.01). In a dose study, supplementation of HIV+ subjects with 4000IU or 7000IU vitamin D/day increased serum 25OHD from 17.3±8.0 and 20.6±6.2ng/ml (43nM and 51nM) at baseline to 41.1±12.0 and 51.9±23.1ng/ml (103nM and 130nM) after 12 weeks (both p<0.001). Greater percent change from baseline 25OHD was significantly associated with enhanced TLR2/1L-induced monocyte CAMP adjusted for baseline expression (p=0.009). In a randomized placebo-controlled trial, 7000IU vitamin D/day increased serum 25OHD from 18.0±8.6 to 32.7±13.8ng/ml (45nM and 82nM) after 12 weeks. Expression of CAMP increased significantly from baseline after 52 weeks of vitamin D-supplementation. At this time point, TLR2/1L-induced CAMP was positively associated with percent change from baseline in 25OHD (p=0.029 overall and 0.002 within vitamin D-supplemented only). These data indicate that vitamin D supplementation in HIV-infected subjects can promote improved antibacterial immunity, but also suggest that longer periods of supplementation are required to achieve this.

High-dose vitamin D3 supplementation in children and young adults with HIV: a randomized, placebo-controlled trial.

BACKGROUND: Suboptimal vitamin D status is prevalent in HIV-infected patients and associated with increased risk of disease severity and morbidity. We aimed to determine 12-month safety and efficacy of daily 7000 IU vitamin D3 (vitD3) versus placebo to sustain increased serum 25-hydroxyvitamin D (25(OH)D) and improve immune status in HIV-infected subjects. METHODS: This was a double-blind trial of perinatally acquired HIV (PHIV)-infected subjects or behaviorally acquired HIV (BHIV)-infected subjects (5.0-24.9 years). Safety, 25(OH)D-related parameters and immune status were assessed at baseline, 3, 6 and 12 months. RESULTS: Fifty-eight subjects enrolled (67% male, 85% African American and 64% BHIV) and 50 completed with no safety concerns. In unadjusted analyses, there were no differences between randomization groups at baseline; at 3, 6 and 12 months, 25(OH)D was higher with supplementation than baseline and higher than with placebo (P < 0.05). In adjusted mixed models, in the supplementation group, the fixed effect of 25(OH)D was higher (P < 0.001). Percentage of naive T-helper cells (Th naive%) were significantly (P < 0.01) and T-helper cells (CD4%) marginally (P < 0.10) increased with supplementation in those taking highly active antiretroviral therapy (HAART), and RNA viral load was reduced (P ≤ 0.05). In exploratory linear models, change in 25(OH)D predicted RNA viral load at 3 and 12 months and CD4% at 3 months (P < 0.05). CONCLUSIONS: Daily 7000 IU vitD3 for 12 months was safe in HIV-infected subjects and effective in increasing 25(OH)D. Supplementation improved some clinically important HIV immune markers in subjects on HAART. Adjunct therapy with high-dose, daily vitD3 for HIV-infected subjects and for those on/off HAART requires further investigation.

Safety and Efficacy of High-Dose Daily Vitamin D3 Supplementation in Children and Young Adults Infected With Human Immunodeficiency Virus.

BACKGROUND: Suboptimal vitamin D (vitD) status is common in children and young adults infected with human immunodeficiency virus (HIV). The vitD supplemental dose needed to normalize vitD status in this population is unknown. METHODS: In this double-blind trial, subjects infected with HIV ages 8.3 to 24.9 years were randomized to vitD3 supplementation of 4000 IU/day or 7000 IU/day and evaluated at 6 and 12 week for changes in vitD status and HIV indicators. A dose was considered unsafe if serum calcium was elevated (above age and sex-specific range) associated with elevated serum 25 hydroxyvitamin D (25(OH)D); >160 ng/mL). RESULTS: At baseline, 95% of subjects (n = 44; 43% with perinatally acquired HIV, 57% with behaviorally acquired HIV) had a suboptimal serum 25(OH)D concentration of <32 ng/mL (mean ± standard deviation, 19.3 ± 7.4; range, 4.4-33.6 ng/mL). After 12 weeks (main outcome) of D3 supplementation, both D3 doses were safe and well tolerated, with no evidence of elevation of serum calcium concentrations or deterioration in HIV immunologic or virologic status. Sufficient vitD status, defined as serum 25(OH)D ≥32 ng/mL, was achieved in 81% of all subjects, and only the 7000 IU/day group (86%) achieved this a priori efficacy criterion in >80% of subjects. Change in serum 25(OH)D did not differ between HIV acquisition groups. CONCLUSIONS: A 7000 IU/day D3 supplementation was safe and effective in children and young adults infected with HIV.

Blood lead concentration is not altered by high-dose vitamin D supplementation in children and young adults with HIV.

OBJECTIVES: Optimal vitamin D status is known to have beneficial health effects and vitamin D supplements are commonly used. It has been suggested that vitamin D supplementation may increase blood lead in children and adults with previous lead exposure. The objective was to determine the safety regarding lead toxicity during 12 weeks of high-dose vitamin D3 supplementation in children and young adults with human immunodeficiency virus (HIV). METHODS: Subjects with HIV (8-24 years) were randomized to vitamin D3 supplementation of 4000 or 7000 IU/day and followed at 6 and 12 weeks for changes in serum 25-hydroxy vitamin D (25D) and whole-blood lead concentration. This was a secondary analysis of a larger study of vitamin D3 supplementation in children and adolescents with HIV. RESULTS: In 44 subjects (75% African American), the baseline mean ± standard deviation serum 25D was 48.3±18.6 nmol/L. Fifty percent of subjects had baseline serum 25D <50.0 nmol/L. Serum 25D increased significantly with D3 supplementation during the 12 weeks. No subject had a whole-blood lead >5.0 µg/dL at baseline or during subsequent visits. Whole-blood lead and 25D were not correlated at baseline, and were negatively correlated after 12 weeks of supplementation (P=0.014). Whole-blood lead did not differ between those receiving 4000 and 7000 IU of vitamin D3. CONCLUSIONS: High-dose vitamin D3 supplementation and the concomitant increased serum 25D did not result in increased whole-blood lead concentration in this sample of children and young adults living in a northeastern urban city.

No improvement in suboptimal vitamin A status with a randomized, double-blind, placebo-controlled trial of vitamin A supplementation in children with sickle cell disease.

BACKGROUND: Suboptimal vitamin A status is prevalent in children with type SS sickle cell disease (SCD-SS) and is associated with hospitalizations and poor growth and hematologic status. The supplemental vitamin A dose that optimizes suboptimal vitamin A status in this population is unknown. OBJECTIVE: The efficacy of Recommended Dietary Allowance (RDA) doses (based on age and sex) of vitamin A (300, 400, or 600 µg retinyl palmitate/d) or vitamin A + zinc (10 or 20 mg zinc sulfate/d) compared with placebo to optimize vitamin A status was assessed in children aged 2.0-12.9 y with SCD-SS and a suboptimal baseline serum retinol concentration (<30 µg/dL). DESIGN: In this randomized, double-blind, placebo-controlled trial, vitamin A status (serum retinol, prealbumin, retinol-binding protein, and relative-dose-response test) and disease-related illness events were assessed. RESULTS: Twelve months of vitamin A supplementation at the doses recommended for healthy US children (based on age and sex) failed to improve serum retinol values in either group (vitamin A: n = 23; vitamin A + zinc: n = 18) compared with placebo (n = 21). By 12 mo, the increase (±SD) in serum retinol (3.6 ± 2.8 µg/dL) in those taking 600 µg vitamin A/d was significantly different from the decrease (±SD; -2.8 ± 2.4 µg/dL) in those taking 300 µg/d, which possibly suggests a dose-response relation (P < 0.05) with RDA doses. CONCLUSIONS: Compared with placebo, 12 mo of vitamin A supplementation at the RDA for healthy children did not improve serum retinol values in children with SCD-SS, which possibly suggests that higher doses are needed. However, the existence of alternative conclusions emphasizes the need for future research.

Vitamin D deficiency and parathyroid hormone levels following renal transplantation in children.

The objectives were to determine the prevalence of vitamin D deficiency [25(OH)D < 10 ng/ml] in pediatric renal transplant (RTx) recipients, compared with controls and identify correlates of changes in 25(OH)D and intact parathyroid hormone (iPTH) levels following transplantation. Serum 25(OH)D, 1,25(OH)(2)D, and iPTH were measured once in 275 healthy controls and at transplantation, and 3 and 12 months posttransplantation in 58 RTx recipients. Multivariate logistic regression models determined the odds ratio (OR) of vitamin D deficiency in RTx recipients vs. controls adjusted for age, sex, race, and season. Generalized estimating equations were used to assess changes following transplantation. At transplantation, 22% of nonblack and 27% of black RTx recipients were vitamin D deficient. The adjusted OR of vitamin D deficiency was greater in RTx recipients (p < 0.001) compared with controls; however, the transplant association was greater in nonblack vs. black individuals (interaction p = 0.02). Overall, 25(OH)D levels did not change significantly following transplantation. Younger age (p < 0.01), nonblack race (p < 0.001), visits in nonwinter months (p < 0.001), and supplementation with ≥400 IU/day ergo/cholecalciferol (p < 0.001) were associated with increases (or lesser declines) in 25(OH)D following transplantation. Increases in 25(OH)D levels (p < 0.001) and vitamin D supplementation (p < 0.01) were associated with greater reductions in iPTH levels following transplantation, independent of 1,25(OH)(2)D levels.

Hypovitaminosis D is associated with greater body mass index and disease activity in pediatric systemic lupus erythematosus.

OBJECTIVES: To determine whether pediatric systemic lupus erythematosus (SLE) is associated with alterations in the vitamin D-parathyroid hormone (PTH) axis and to assess the relation between vitamin D deficiency and SLE activity. STUDY DESIGN: 25-hydroxy vitamin D [25(OH)D], 1,25-dihydroxy vitamin D [1,25(OH)2D], and intact PTH were measured in subjects with SLE (n = 38) and healthy controls (n = 207), ages 5 to 21 years. Vitamin D status and its relation with disease activity were assessed using multivariable logistic and linear regression. RESULTS: Severe vitamin D deficiency (25(OH)D <10 ng/ml) was observed in a significantly higher proportion of subjects with SLE (36.8% vs 9.2%, P < .001). In SLE, the odds ratio (OR) for severe deficiency was 2.37 (P = .09), adjusting for age, sex, race, and season. However, for each 1 SD greater body mass index (BMI) z-score, 25(OH)D levels were 4.2 ng/mL lower (P = .01) in SLE, compared with controls. Adjusting for 25(OH)D levels, SLE was associated with significantly lower 1,25(OH)2D (P < .001) and intact PTH levels (P = .03). Greater SLE disease activity index scores were observed in those with 25(OH)D <20 ng/mL (P = .01). CONCLUSIONS: SLE was associated with vitamin D deficiency, particularly among those subjects with SLE who were overweight. Future studies should assess the effect of vitamin D supplementation on skeletal and nonskeletal outcomes in SLE.

Vitamin A intake and elevated serum retinol levels in children and young adults with cystic fibrosis.

BACKGROUND: Individuals with cystic fibrosis (CF) and pancreatic insufficiency (PI) are at risk for fat-soluble vitamin deficiency, including vitamin A. Recent evidence suggests current practices of vitamin A intake results in elevated serum retinol. METHODS: Serum retinol was assessed in 78 subjects (8 to 25 years old) with CF and PI by high performance liquid chromatography, and compared to the U.S. National Health and Nutrition Examination Survey (NHANES) data of subjects of similar age and gender. Vitamin A intake, anthropometry and FEV(1) were measured, and their relationship to serum retinol status was assessed. RESULTS: Median (range) serum retinol was 80 microg/dL (33 to 208) in subjects with CF; 58% were above the NHANES reference range (30 to 72 microg/dL). Total vitamin A intake from diet and supplements was high (608+431% Recommended Dietary Allowance). Serum retinol was not correlated with vitamin A intake, age or gender, and was inversely correlated with weight and height z scores (r=-0.28, p<0.05) in the subjects with CF. CONCLUSIONS: Both vitamin A intake and serum retinol were elevated in subjects with CF and PI, corroborating recent evidence of elevated serum retinol in preadolescent children with CF. These findings indicate the need for further study of dosing and monitoring care practices of vitamin A, to ensure adequacy and to avoid toxicity.

Vitamin D insufficiency in children, adolescents, and young adults with cystic fibrosis despite routine oral supplementation.

BACKGROUND: Cystic fibrosis (CF) with pancreatic insufficiency is associated with poor absorption of fat and fat-soluble vitamins, including vitamin D. Pancreatic enzyme supplementation does not completely correct fat malabsorption in CF patients. OBJECTIVE: The objective of the study was to compare the vitamin D status of children, adolescents, and young adults with CF who were treated with routine vitamin D and pancreatic enzyme supplements with the vitamin D status of a healthy reference group from a similar geographic area. DESIGN: Growth, dietary intake, and serum concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and parathyroid hormone (PTH) were measured in 101 white subjects with CF and a reference group of 177 white subjects. RESULTS: The median daily vitamin D supplementation in the CF group was 800 IU. The mean +/- SD serum concentrations of 25(OH)D were 20.7 +/- 6.5 ng/mL in the CF group and 26.2 +/- 8.6 ng/mL in the reference group (P < 0.001). Vitamin D deficiency and insufficiency were defined as 25(OH)D concentrations < 11 ng/mL and < 30 ng/mL, respectively. Seven percent of the CF group and 2% of the healthy reference group were vitamin D deficient (P < 0.03). Ninety percent of the CF group and 74% of the healthy reference group were vitamin D insufficient (P < 0.01). Twenty-five percent of the CF group and 9% of the healthy reference group had elevated PTH (P < 0.006). The odds of vitamin D insufficiency in the CF group, compared with the healthy reference group, were 1.2 (95% CI: 1.1, 1.3) after adjustment for season and age. CONCLUSION: Despite daily vitamin D supplementation, serum 25(OH)D concentrations remain low in children, adolescents, and young adults with CF.

Risk factors for low serum 25-hydroxyvitamin D concentrations in otherwise healthy children and adolescents.

BACKGROUND: Serum 25-hydroxyvitamin D [25(OH)D] concentrations serve as a biomarker for vitamin D stores. Prior studies have not examined the risk factors for low vitamin D concentrations in a multiethnic sample of US youth across a broad age range. OBJECTIVE: The objective was to determine the prevalence of and factors associated with low concentrations of 25(OH)D in children and adolescents. DESIGN: Serum 25(OH)D concentrations were measured in 382 healthy children aged 6-21 y living in the northeastern United States. Dietary and supplemental vitamin D intake was assessed by interview. Fat and lean mass were assessed by dual-energy X-ray absorptiometry. Multivariable ordinal logistic regression was used to determine factors associated with decreased concentrations of 25(OH)D. RESULTS: The median concentration of 25(OH)D was 28 ng/mL (interquartile range: 19-35 ng/mL), and 55% of subjects had 25(OH)D concentrations <30 ng/mL. 25(OH)D concentrations were inversely correlated with parathyroid hormone concentrations (Spearman's r=-0.31, P<0.001) but were not significantly correlated with 1,25-dihydroxyvitamin D concentrations. In the multivariable model, older age (P<0.001), black race [odds ratio (OR): 14.2; 95% CI: 8.53, 23.5], wintertime study visit (OR: 3.55; 95% CI: 2.29, 5.50), and total daily vitamin D intake <200 IU (OR: 1.58; 95% CI: 1.02, 2.46) were associated with low vitamin D concentrations. Fat and lean mass were not independently associated with vitamin D status in this healthy-weight sample. CONCLUSION: Low serum 25(OH)D concentrations are prevalent in otherwise healthy children and adolescents in the northeastern United States and are related to low vitamin D intake, race, and season.

Plasma zinc and growth status in preadolescent children with cystic fibrosis.

OBJECTIVE: To investigate plasma zinc status in relation to dietary and supplemental zinc intake, growth and pulmonary status in preadolescent children with cystic fibrosis (CF) and pancreatic insufficiency (PI). METHODS: Fasting plasma zinc was assessed in children (age, 8-11 years) with CF and PI. Food (7-day weighed records) and supplemental zinc intake, serum alkaline phosphatase and albumin, pulmonary function (spirometry), coefficient of fat absorption (%COA, 72-hour fecal fat) and growth status [height adjusted for genetic potential (AHAZ), weight (WAZ) and BMI Z scores (BMIZ)] were assessed. RESULTS: For the 62 children (32 males), mean plasma zinc (+/-SD) was 16.8 +/- 3.1 micromol/L (110 +/- 20 ug/dL). Sixty-five percent of the subjects had levels above the study reference range of 9.2 to 15.3 micromol/L (60-100 ug/dL); no subjects had low zinc levels. Median (range) total daily zinc intake was 279% (83-988%) recommended dietary allowance, growth status was suboptimal (mean +/- SD: AHAZ, -0.8 +/- 1.0; WAZ, -0.5 +/- 1.2; BMIZ, -0.2 +/- 1.1), and forced expiratory volume at 1 second (FEV1) was 92 +/- 13% predicted. Plasma zinc was not correlated with growth, pulmonary or alkaline phosphatase status. Plasma zinc was correlated with serum albumin (r = 0.25, P < 0.05) and was inversely correlated with coefficient of fat absorption (as %; r = -0.30, P = 0.02). CONCLUSIONS: Under current patterns of care in CF Centers, total zinc intake and plasma zinc status were adequate. These findings suggest that zinc was not a limiting micronutrient for preadolescent children with CF and PI and mild-to-moderate lung disease, and not likely contributing to their suboptimal growth status.