Suboptimal Vitamin Research Articles

High Prevalence of Suboptimal Vitamin D Status and Bone Loss in Adult Short Bowel Syndrome Even After Weaning Off Parenteral Nutrition.

Previous studies have noticed the high incidence of suboptimal vitamin D (VtD) status and bone loss in short bowel syndrome (SBS) with parenteral nutrition (PN) dependence. However, limited data have focused on adult SBS without PN dependence. Therefore, our objective was to investigate the incidence and risk factors of suboptimal VtD status and bone loss in adult SBS even after weaning off PN. We performed a prospective study of 60 adult patients with SBS. Serum 25-hydroxyvitamin D (25-OHD) was measured by radioimmunoassay. Bone mineral density (BMD) was measured using dual-energy x-ray absorptiometry (DEXA). Medical records and various laboratory parameters were collected in all participants. Suboptimal VtD status was identified in all individuals, including 3 (5.0%) with VtD insufficiency and 57 (95.0%) with VtD deficiency. Residual small bowel length (B, 0.072, P = .001) and duration of SBS (B, -0.066, P = .020) were both significantly correlated with suboptimal VtD levels. Overall, only 2 patients presented a normal BMD; osteopenia and osteoporosis were noted in 41 (68.3%) and 17 (28.3%) individuals, respectively. Low 25-OHD concentration was associated with a decreased BMD (B, 0.065, P = .029). There were no other demographic characteristics or clinical examinations associated with suboptimal VtD levels and bone loss. Suboptimal VtD status and bone loss were common in adult SBS even after weaning off PN. Despite routine oral VtD supplementation, most patients did not achieve satisfactory status. This emphasizes the critical importance of routine surveillance of 25-OHD and BMD, as well as consideration of alternative methods of supplementation after weaning off PN.

Reduced bone resorption by intake of dietary vitamin D and K from tailor-made Atlantic salmon: A randomized intervention trial.

Suboptimal vitamin D status is common among humans, and might increase bone resorption with subsequent negative effects on bone health. Fatty fish, including Atlantic salmon, is an important dietary vitamin D source. However, due to a considerable change in fish feed composition, the contribution of vitamin D from salmon fillet has been reduced. The main objective was to investigate if intake of vitamin D3 enriched salmon or vitamin D3 tablets decreased bone biomarkers (urinary N-telopeptides, deoxypyridinoline, serum bone-specific alkaline phosphatase, and osteocalcin) compared to a low vitamin D3 intake. The 122 healthy postmenopausal women included in this 12 weeks intervention trial were randomized into four groups: three salmon groups (150 grams/two times/week) and one tablet group (800 IU vitamin D and 1000 mg calcium/day). The salmon groups also received calcium supplements. The salmon had three different vitamin D3/vitamin K1 combinations: high D3+high K1, low D3+high K1, or high D3+low K1. Increased intake of salmon containing high levels of vitamin D3 (0.35-0.38 mg/kg/fillet) and supplements with the same weekly contribution had a positive influence on bone health as measured by bone biomarkers in postmenopausal women. Consequently, an increased level of vitamin D3 at least to original level in feed for salmonids will contribute to an improved vitamin D3 status and may improve human bone health.

Impact of Tenofovir Disoproxil Fumarate on Bone Metabolism and Bone Mass among Perinatally HIV-Infected Asian Adolescents

This study aimed to determine the effect of tenofovir disoproxil fumarate (TDF) on bone metabolism and bone mass in HIV-infected adolescents. This was a sub-study of a cross-sectional multicentre bone health trial that enrolled perinatally HIV-infected Thai and Indonesian adolescents (10-18 years) with viral suppression on antiretroviral therapy. Participants were classified into two groups as TDF users and non-users. Bone metabolism-related markers (25-hydroxyvitamin D [25-OHD], intact parathyroid hormone [iPTH], bone turnover biomarkers), and lumbar spine dual-energy X-ray absorptiometry were assessed. Bone mineral density (BMD)/bone mineral apparent density (BMAD) Z-scores were calculated. Of 394 adolescents, 136 (34.5%) and 258 (65.5%) were TDF users and non-users, respectively. Among TDF users, median age (IQR) was 16.1 (14.7-17.4) years and TDF treatment duration (IQR) was 2.3 (1.4-3.1) years. Among TDF non-users, median age (IQR) was 14.3 (12.6-16.4) years. BMD and BMAD Z-scores comparing TDF users with non-users were -0.8 and -0.6 (P=0.27), and -0.3 and -0.2 (P=0.58), respectively. The association between TDF use and iPTH elevation was intensified in adolescents with suboptimal vitamin D levels (25-OHD <30 ng/ml; P=0.001). TDF administration was positively associated with bone resorption marker (P=0.04) and negatively associated with bone formation marker (P=0.04). With data up to 4 years, neither association between TDF use and bone mass loss (BMD: P=0.09; BMAD: P=0.22), nor variation of bone mass Z-scores by TDF treatment duration (BMD: P=0.34; BMAD: P=0.58) was demonstrated. Recent TDF administration was correlated with PTH elevation and bone turnover dysregulation but not with bone mass reduction in our cohort. A study with extended follow-up to ascertain TDF-associated bone mass deterioration is warranted.

Bone Mineral Density and Fat-Soluble Vitamin Status in Adults with Cystic Fibrosis Undergoing Lung Transplantation: A Pilot Study.

Patients with cystic fibrosis (CF) often experience low bone mineral density (BMD) pre- and post-lung transplantation (LTX). The study purpose was to describe BMD and micronutrient status in adults with CF pre- and post-LTX. Twelve patients with CF (29 ± 8 years) were recruited from the CF clinic at the University of Alberta Lung Transplant Program. BMD and vitamins A, D, E, K status, and parathyroid hormone were measured pre- and post-LTX. No significant differences pre- and post-LTX were observed at the different bone sites measured (lumber-spine, femoral-neck (FN), hip, and femoral-trochlea) (P > 0.05). BMD T-scores (<-2) was present in lumbar-spine, FN, hip, and femoral-trochlea in 33%, 17%, 17%, and 25% of individuals pre-LTX and 58%, 33%, 58%, and 33% of individuals post-LTX, respectively. More than 50% of patients had suboptimal vitamin K levels (PIVKA-II values >3 ng/mL) pre- and post-LTX. Adults with CF pre- and post-LTX had reduced BMD and suboptimal vitamin K status.

Serum vitamin C and spinal pain: a nationwide study.

Back pain brings about one of the heaviest burden of disease. Despite much research, this condition remains poorly understood, and effective treatments are frustratingly elusive. Thus, researchers in the field need to consider new hypotheses. Vitamin C (ascorbic acid) is an essential cofactor for collagen crosslinks, a key determinant of ligament, tendon, and bone quality. Recent studies have reported high frequency of hypovitaminosis C in the general population. We hypothesized that lack of vitamin C contributes to poor collagen properties and back pain. We conducted this study to examine the associations between serum concentration of vitamin C and the prevalence of spinal pain and related functional limitations in the adult general population. This study used nationwide cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES) 2003-2004. Data were available for 4742 individuals aged ≥20 years. Suboptimal serum vitamin C concentrations were associated with the prevalence of neck pain (adjusted odds ratio [aOR]: 1.5; 95% confidence interval [CI]: 1.2-2.0), low back pain (aOR: 1.3; 95% CI: 1.0-1.6), and low back pain with pain below knee (aOR: 1.3; 95% CI: 1.0-1.9) in the past 3 months, self-reported diagnosis of arthritis/rheumatism (aOR: 1.4; 95% CI: 1.2-1.7), and related functional limitations' score (adjusted difference of means [aB]: 0.03; 95% CI: 0.00-0.05). The prevalence of hypovitaminosis C in the general population is high. Our study shows associations between vitamin C and spinal pain that warrant further investigation to determine the possible importance of vitamin C in the treatment of back pain patients.

Suboptimal Vitamin D levels among adult survivors of childhood cancers

Purpose: Vitamin D plays an important role in many bodily systems, with increasing evidence suggesting its importance for the prevention of chronic diseases and cancer. The identification of vitamin D levels in childhood cancer survivors becomes, therefore, particularly relevant, given that optimizing levels may contribute to the prevention of secondary malignancies and chronic diseases. Methods: A cross - sectional analysis of serum 25 - hydroxyvitamin D levels among adult survivors of childhood cancers living in New York State and surrounding areas (n = 139) was performed. Independent variables included gender, race/ethnicity, cancer site, year of diagnosis, past medical and surgical history, prior radiation therapy; prior chemotherapy, age at diagnosis, age at last clinic visit, year of last clinic visit, height, weight, body mass index, and vitamin D supplementation. Results: Overall, 34% of survivors were vitamin D deficient ( 25 demonstrated lower levels of vitamin D (p < 0.05). Vitamin D levels did not vary by age group, race, ethnicity, diagnosis, or years since diagnosis. Conclusion: Given the growing awareness of the role of vitamin D and the documented late effects of treatment for childhood cancers, the high prevalence of vitamin D deficiency within the childhood cancer survivor population is of concern. Vitamin D represents an important target for surveillance and intervention to help improve long - term outcomes of childhood cancer survivors.

PWE-023 Vitamin D Enhances The Ability of Anti-TNF Therapy to Suppress Dendritic Cell Activity in Crohn’s Disease

Introduction Dendritic cells (DC) can determine whether the mucosal immune system mounts an inflammatory or regulatory response to antigen and may contribute to the pathogenesis of Crohn’s disease. Vitamin D down-regulates DC inflammatory responses and could prove beneficial as a treatment adjunct in Crohn’s. This study assessed the effect of high dose parenteral vitamin D treatment on circulating DC phenotype and function in patients with active luminal Crohn’s receiving anti-TNFα therapy. Methods Peripheral blood mononuclear cells were isolated from 13 patients with active luminal Crohn’s and suboptimal vitamin D levels prior to and 6 weeks after starting anti-TNFα (infliximab) therapy. Patients with low vitamin D ( 2 vitamin D3). Flow cytometry was used to identify total DC, (HLA-DR + cells negative for markers of other cell lineages (CD3, CD14, CD16, CD19 & CD34)). DC were further subtyped as myeloid (mDC, CD11c + CD123 − ). Expression of phenotypic markers (including maturation and homing markers and pattern recognition receptors) and on-going DC cytokine production during 4 hours’ culture were assessed. Results Production of TNFα by myeloid DC was significantly reduced (p = 0.016 Fig C) in those patients who received vitamin D alongside anti-TNFα therapy; without vitamin D treatment, TNFα production by myeloid DC did not decrease significantly after anti-TNFα therapy (p = 0.96 Fig B). There was a significant negative correlation between change in vitamin D level and change in TNFα production by myeloid DC (p = 0.025, correlation coefficient =0.68 Fig D). An increase of serum 25(OH)vitamin D greater than 20 nmol/m was associated with a decrease in myeloid DC TNFα production. Anti-TNFα therapy alone induced a significant upregulation of the skin homing marker cutaneous lymphocyte antigen (CLA) on myeloid DC (p = 0.0055), an effect which was not seen in patients receiving adjunctive vitamin D. Conclusion High doses of parenteral vitamin D in patients with Crohn’s promotes anti-TNFα down-regulation of circulating myeloid DC production of TNFα which may influence the subsequent interaction of DC and T cells. TNFα promotes a TH-1/ TH-17 response characteristic of Crohn’s inflammation; thus the ability of vitamin D to further block TNFα production may promote a more regulatory T cell response and improve outcomes when used as an adjunct to anti-TNFα therapy. The down-regulation of skin homing marker CLA by vitamin D may be clinically useful in those patients suffering cutaneous sequelae of anti-TNFα therapy. Disclosure of Interest None Declared

Factors influencing the late phase of recovery after bone mineral density loss in allogeneic stem cell transplantation survivors.

Accelerated bone mineral density loss (BMDL) occurs early after allogeneic stem cell transplantation (SCT) and is related to factors such as steroids and chronic GvHD. In order to understand the natural history of BMDL of SCT in the longer term, we evaluated a longitudinal cohort of 148 survivors with a median follow-up of 12 years (range 3-22 years). All women received hormone replacement therapy, and routine calcium/vitamin D supplementation was recommended but ∼50% of patients still had suboptimal vitamin D levels and bisphosphonates were rarely utilized. BMD significantly improved from 5 to 20+ years but the femoral neck and forearm remained vulnerable sites. Younger age, higher pretransplant body mass index (BMI) and increment in BMI post transplant were significantly associated with increased BMD and protected against osteopenia/osteoporosis. These findings support consideration of BMD loss in SCT survivors in two phases, an early phase of BMD loss (3-5 years) followed by a later phase of BMD recovery, with different protective and aggravating factors. Treatment- and transplant-related factors (such as steroids, immunosuppressives, chronic GvHD, vitamin D) are known to impact the early phase of BMD loss but age and BMI are more influential in the late phase of BMD recovery.

Placental Megalin and Cubilin Expression is Associated with Markers of Vitamin D Status but Not Fetal Bone Growth During Adolescent Pregnancy

Megalin and cubilin are highly expressed in the human placenta and may be involved in modulating maternal‐fetal 25(OH)D status. Few studies have focused on the expression of these transporters and associations with vitamin D‐related outcomes during pregnancy. The purpose of this study was to characterize placental transcript expression of megalin and cubilin in a cohort of pregnant adolescents with suboptimal vitamin D status and evaluate their relationships with markers of maternal and neonatal vitamin D status and fetal bone growth. Placental tissue was obtained at delivery from pregnant adolescents (n=86; age ≤18 y) enrolled in a longitudinal study designed to assess maternal and fetal bone health in Rochester, New York. During pregnancy, teens completed up to three study visits during which maternal anthropometrics and bone quality (heel ultrasound) and standard fetal biometry measures (sonography) were obtained. Maternal serum obtained at mid‐gestation (MG; 26.2 ± 3.5 gestational weeks (GW)) and delivery (39.9 ± 1.2 GW) and cord blood collected at delivery were analyzed for 25(OH)D (Diasorin assay), 1,25(OH)2D (thymus receptor binding assay), PTH (ELISA), NTX (ELISA), osteoprotegerin (ELISA) and osteocalcin (RIA) concentrations. RNA was extracted from placental tissue and real‐time PCR reactions were performed in triplicate using megalin and cubilin‐specific primers (sequence ID numbers NM_004525.2 and NM_001081.3, respectively). Beta‐actin was used as an endogenous control (sequence ID NM_001101.2). Non‐parametric comparisons were completed using Wilcoxon rank sums and Chi‐square statistics, while two‐sample t tests and ANOVA were used for parametric comparisons. Pearson and Spearman correlations were used to assess associations between placenta transcript expression and maternal and fetal characteristics. This was a diverse cohort with 53 (61.6%) and 33 (38.4%) teens self‐reporting as African American and Caucasian, respectively; a total of 24 (27.9%) reported being Hispanic. Cubilin and megalin transcript expression were positively correlated with one another (r=0.294, p=0.006). Megalin and cubilin expression were not significantly associated with in utero fetal growth, infant birth weight and length, or measures of maternal heel bone quality. Significant positive associations were observed between placental cubilin expression and 1‐alpha hydroxylase (r=0.251, p&lt;0.030) and 24‐hydroxylase (r=0.254, p=0.028) mRNA expression. Both megalin and cubilin mRNA levels were significantly negatively associated with maternal serum 1,25(OH)2D (r= −0.359, p=0.007 and r= −0.299, p=0.027, respectively) but not fetal 1,25(OH)2D or maternal and fetal 25(OH)D. Megalin transcript expression was also negatively associated with PTH concentrations in cord blood (r= −0.444, p=0.026) but not maternal PTH at MG or delivery. Pregnant teens with lower circulating 1,25(OH)2D had greater expression of megalin and cubilin mRNA suggestive of prenatal regulatory mechanisms to maintain maternal and fetal vitamin D status.Support or Funding InformationFunded by USDA/NIFA Grant No. 2012‐67012‐19815

Short-Term Vitamin B-6 Restriction Does Not Affect Plasma Concentrations of Hydrogen Sulfide Biomarkers Lanthionine and Homolanthionine in Healthy Men and Women

Background: Suboptimal vitamin B-6 status is associated with increased cardiovascular disease risk, although the mechanism is unknown. The synthesis of the vasodilator hydrogen sulfide occurs through side reactions of the transsulfuration enzymes cystathionine β-synthase and cystathionine γ-lyase, with pyridoxal 5′-phosphate as a coenzyme. Two proposed hydrogen sulfide biomarkers, lanthionine and homolanthionine, are produced concurrently.Objective: To determine whether hydrogen sulfide production is reduced by vitamin B-6 deficiency, we examined the relations between plasma concentrations of lanthionine and homolanthionine, along with other components of the transsulfuration pathway (homocysteine, cystathionine, and Cys), in a secondary analysis of samples from 2 vitamin B-6 restriction studies in healthy men and women.Methods: Metabolite concentrations were measured in plasma from 23 healthy adults (12 men and 11 women) before and after 28-d controlled dietary vitamin B-6 restriction (0.37 ± 0.04 mg/d). Vitamin B-6 restriction effects on lanthionine and homolanthionine concentrations were assessed. Associations between hydrogen sulfide biomarkers, transsulfuration metabolites, and functional indicators of vitamin B-6 deficiency were analyzed by linear regression.Results: Preprandial plasma lanthionine and homolanthionine concentrations ranged from 89.0 to 372 nmol/L and 5.75 to 32.3 nmol/L, respectively, in healthy adults. Mean lanthionine and homolanthionine concentrations were not affected by vitamin B-6 restriction (P < 0.66), with marked heterogeneity of individual responses. After restriction, homolanthionine was positively associated with functional indicators of vitamin B-6 deficiency, which differed from hypothesized negative associations. Plasma lanthionine was positively correlated with the concentration of its precursor, Cys, before (R2 = 0.36; P = 0.002) and after (R2 = 0.37; P = 0.002) restriction. Likewise, homolanthionine concentration was positively correlated with its precursor homocysteine, but only in vitamin B-6 adequacy (R2 = 0.41; P < 0.001).Conclusions: The resiliency of plasma lanthionine and homolanthionine concentrations after short-term vitamin B-6 restriction suggests a minimal effect of moderate vitamin B-6 deficiency on hydrogen sulfide production. Additional research is needed to better understand the metabolism and disposal of these biomarkers in humans. This study was registered at clinicaltrials.gov as NCT00877812.

Prevalence and determinants of suboptimal vitamin B6 status in young adult women in Metro Vancouver

BackgroundVitamin B6 (B‐6) adequacy is crucial for life‐long health. The biologically active form of B‐6, pyridoxal 5′‐phosphate (PLP), plays an essential role in the metabolism of amino acids, synthesis of neurotransmitters, regulation of energy homeostasis, and metabolism of heme. Suboptimal B‐6 status – defined as having plasma PLP concentration between 20–30 nmol/L – has been associated with an increased risk of cardiovascular disease and breast, prostate, and colorectal cancer. Maternal B‐6 status has been positively associated with infant birth health determined by the Apgar Score. Low preconceptional B‐6 status has been associated with an increased risk of preterm birth, early pregnancy loss, and reduced probability of conception. Given an estimated 50% of pregnancies are unplanned, it is important for women to maintain an adequate B‐6 status throughout reproductive years. In the US National Health and Nutrition Examination Survey (NHANES 2003–2004), over 40% of B‐6 deficiency – defined as having plasma PLP concentration &lt;20 nmol/L – was reported in childbearing‐aged women (21–44 y). Despite the crucial role of B‐6 in health, there are few data on B‐6 status among Canadian women.ObjectiveTo assess the prevalence of B‐6 deficiency and determinants of B‐6 status in childbearing‐aged women in Metro Vancouver, British Columbia.MethodsData were derived from a descriptive cross‐sectional study using convenience sampling of self‐reported healthy, non‐pregnant women (19–35 y; n= 202) residing in Metro Vancouver. The enrolment was conducted between 2012 and 2013 (Quay et al. 2015 APNM). Vitamin B‐6 status was assessed by determining fasting plasma PLP concentrations. Information on demographic, lifestyle and dietary intake was collected through validated questionnaires.ResultsThe prevalence of B‐6 deficiency (plasma PLP &lt; 20 nmol/L) was 1.5% and that of suboptimal B‐6 status (plasma PLP between 20–30 nmol/L) was 10.9% in these healthy women of European (73%) and South Asian (27%) descent. Mean (± SD) plasma PLP concentration was 61 ± 2.1 nmol/L. Overall, the subjects were highly educated (28% &gt; bachelor's degree; 72% ≤ bachelor's degree) and 23% reported the use of B6 containing vitamin supplements. Body mass index (p value &lt; 0.05), ethnicity (p value &lt; 0.05), dietary B‐6 intake (p value &lt; 0.05) and the use of supplemental B‐6 (p value &lt; 0.001) were significant determinants of plasma PLP concentrations. Mean dietary B‐6 intake was 1.5 ± 0.45 mg/d; and 21% had a dietary B‐6 intake below the estimated average requirement (EAR; 1.1mg/day).ConclusionThe overall 12.4% of low B‐6 status (plasma PLP &lt; 30 nmol/L) indicates a need for investigating B‐6 status in a representative sample of Canadians. Ethnicity, dietary B‐6 intake and the use of supplemental B‐6 should be considered as covariates in future studies.Support or Funding InformationSupported by the ‘Food Nutrition and Health Vitamin Research Fund’, Faculty of Land and Food Systems, The University of British Columbia

Clinical correlates of vitamin D deficiency in established psychosis.

BackgroundSuboptimal vitamin D levels have been identified in populations with psychotic disorders.We sought to explore the relationship between vitamin D deficiency, clinical characteristics and cardiovascular disease risk factors among people with established psychosis.MethodsVitamin D levels were measured in 324 community dwelling individuals in England with established psychotic disorders, along with measures of mental health, cardiovascular risk and lifestyle choices. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25-OHD) levels below 10 ng/ml (equivalent to <25 nmol/L) and “sufficient” Vitamin D as above 30 ng/ml (>50 nmol/L).ResultsThe mean 25-OHD serum level was 12.4 (SD 7.3) ng/ml, (range 4.0-51.7 ng/ml). Forty nine percent (n = 158) were vitamin D deficient, with only 14 % (n = 45) meeting criteria for sufficiency. Accounting for age, gender, ethnicity and season of sampling, serum 25-OHD levels were negatively correlated with waist circumference (r = −0.220, p < 0.002), triglycerides (r = −0.160, p = 0.024), total cholesterol (r = −0.144, p = 0.043), fasting glucose (r = −0.191, p = 0.007), HbA1c (r = −0.183, p = 0.01), and serum CRP levels (r = −0.211, p = 0.003) and were linked to the presence of metabolic syndrome.ConclusionsThis is the largest cross sectional study of serum 25-OHD levels in community dwelling individuals with established psychosis, indicating a high level of vitamin D deficiency. Lower vitamin D levels are associated with increased cardiovascular disease risk factors and in particular metabolic syndrome. Further research is needed to define appropriate protocols for vitamin D testing and supplementation in practice to see if this can improve cardiovascular disease risk.Trial registrationISRCTN number is ISRCTN58667926 Date of registration: 23/04/2010

Traditional foods and 25(OH)D concentrations in a subarctic First Nations community

BackgroundSub-optimal vitamin D status is common worldwide and the condition may be associated with increased risk for various chronic diseases. In particular, low vitamin D status is highly prevalent in indigenous communities in Canada, although limited data are available on the determinants of serum 25-hydroxyvitamin D (25(OH)D) concentrations in this population. The relationship between traditional food consumption and vitamin D status has not been well documented.ObjectiveTo investigate the determinants of serum 25(OH)D status in a First Nations community in Ontario, Canada, with a focus on the role of traditional food consumption and activities.MethodsA cross-sectional analysis was conducted within the Sandy Lake Health and Diabetes Project (2003–2005). A total of 445 participants (>12 years of age) were assessed for serum 25(OH)D status, anthropometric and lifestyle variables, including traditional and non-traditional dietary practices and activities. Diet patterns were identified using factor analysis, and multivariate linear regression analysis was used to analyse the determinants of 25(OH)D concentrations.ResultsMean serum 25(OH)D concentrations were 22.1 nmol/L (16.9, 29.9 nmol/L) in men and 20.5 nmol/L (16.0, 27.3 nmol/L) in women. Multivariate determinants of higher serum 25(OH)D included higher consumption of traditional and healthier market foods, higher wild fish consumption, male gender, spring/summer season of blood collection and more frequent physical activity. Significant negative determinants included hours of TV/day, higher BMI and higher consumption of unhealthy market foods.ConclusionsTraditional food consumption contributed independently to higher 25(OH)D concentrations in a First Nations community with a high prevalence of sub-optimal vitamin D status.

Effect of Antiepileptic Therapy on Serum 25(OH)D3 and 24,25(OH)2D3 Levels in Epileptic Children

Background: Vitamin D deficiency is not only associated with the adverse effects of chronic treatment with antiepileptic drugs (AEDs), but also with epilepsy. Although emerging evidence suggests that AEDs can accelerate the vitamin D catabolism, resulting in suboptimal vitamin D status, there are a limited number of studies examining the vitamin D status in epileptic patients, especially in first-episode or AEDs-naïve children. Methods: Determined with high-performance liquid chromatography-tandem mass spectrometry, circulating 25(OH)D₃ and 24,25(OH)₂D₃ levels, and 24,25(OH)₂D₃:25(OH)D₃ ratio were compared between AEDs-treated epileptic (n = 363) and control (n = 159) children. To further figure out whether the patients were in a vitamin D deficient prone state even before treatment, epileptic children before their initiation of treatment (n = 51) were enrolled into a follow-up study. Results: A significant decrease of 25(OH)D₃ and 24,25(OH)₂D₃ levels, but a significant increase of 24,25(OH)₂D₃:25(OH)D₃ ratio was observed in epileptic children, compared with controls. Baseline 25(OH)D₃, 24,25(OH)₂D₃ and 24,25(OH)₂D₃:25(OH)D₃ ratio in the follow-up group were similar to those in controls, but significantly changed with 2 months of AED therapy. Conclusions: Disturbed vitamin D levels were possibly the consequence of AED therapy, rather than the contributing factor of epilepsy. Collectively, circulating vitamin D levels should be monitored and corrected in AEDs-treated epileptic children.

To study the masking effect of folic acid on Vitamin B12deficiency anemia

Background and Aim: A deficiency of either Vitamin B 12 or folate can lead to megaloblastic anemia. Folate and Vitamin B 12 metabolism is linked in transfer of a methyl group from N5-methyltetrahydrofolate to cobalamin. Methods: This was an observational study carried out among healthy adults (students and staff) of a medical college in rural Northwest India. Results: Despite the occurrence of suboptimal serum Vitamin B 12 in more than half of our healthy study population on one hand, we observed normal hematological variables such as hemoglobin or lack red blood cell macrocytosis (mean corpuscular volume > 100 fL) among participants as a rule. Folic acid deficiency usually coexists with that of Vitamin B 12 , and this has been reported by many studies in past. Strikingly, our study population had 16.98 ± 5.44 ng/ml as mean serum folic acid which was toward higher side of normal range. This sufficiency of folic acid in the group having suboptimal Vitamin B 12 might have masked the manifestations of Vitamin B 12 deficiency. Conclusion: The sufficiency of folic acid in the study group might have masked the overt manifestations of Vitamin B 12 deficiency.

Low 25-Hydroxyvitamin D Levels in Children with Spina Bifida.

To determine vitamin D status in children with spina bifida (SB). Charts of all patients with SB at the Shriners Hospital for Children in Houston, Texas, seen between July 2011 and June 2013 were retrospectively reviewed. Daily intake of milk, vitamins, amount of screen time, and time spent outdoors were recorded along with height, weight, body mass index, and serum vitamin D levels. A total of 38 patients were identified. The mean level of vitamin D was 58.8 nmol/L (23.5 ng/dL); 30 (81%) had insufficient levels, 50 to 75 nmol/L (20 to 30 ng/mL), or deficient levels, <50 nmol/L (<20 ng/mL). African American and Hispanic descent correlated with decreased levels (P = 0.017). Daily vitamin D supplementation correlated with increased levels (P = 0.046). Most children with SB have suboptimal vitamin D levels. Despite living in a sunny climate and spending at least 15 minutes per day outdoors, children with SB have suboptimal vitamin D levels. Healthcare providers should consider the routine measurement of vitamin D levels and advise supplementation accordingly in this patient population.

Effect of cholecalciferol supplementation on urine podocyte-associated messenger RNAs in patients with chronic kidney disease.

Vitamin D reduces albuminuria in patients with chronic kidney disease (CKD) but its effects on glomerular podocytes are not entirely understood. To evaluate if cholecalciferol supplementation reduces the levels of podocyte-associated urine mRNAs in patients with CKD. A total of 27 patients with stages 2 to 4 CKD and suboptimal serum vitamin D [25(OH)D] levels were treated with cholecalciferol for 6 months. Serum 25(OH)D level, estimated glomerular filtration rate (eGFR), proteinuria, and urine mRNA of nephrin, podocin, podocalyxin, transient receptor potential cation channel 6, vascular endothelial growth factor A, and transforming growth factor beta were assessed before and after intervention. eGFR declined at an average rate of -4.71 mL/min/1.73 m2 (p = 0.010 vs. baseline), being 28 ± 16 mL/min/1.73 m2 at six months. No changes in proteinuria or mineral and bone metabolism parameters were observed after cholecalciferol supplementation. Urinary podocyte-associated mRNAs did not change significantly after treatment. However, patients who achieved 25(OH)D level > 20 ng/mL at six months showed a trend of reduction of urinary nephrin and podocin mRNA levels; in patients with 25(OH)D that remained < 20 ng/mL there was a significant increase in urinary podocalyxin, and a trend of higher expression of urinary nephrin and podocin mRNA. Six months of cholecalciferol supplementation had no effect on urine podocyte-associated mRNA profile of patients with advanced CKD. The protective effect of vitamin D or its analogues on the glomerular podocyte should be investigated in early stages of CKD with a longer treatment period.

Nutritional Status and Nutrient Intake Challenges in Children With Spinal Muscular Atrophy

BackgroundNutrition is recognized as a core component of multidisciplinary care for patients with spinal muscular atrophy, but specific nutritional challenges in this population are not well described. We aimed to describe the nutritional status and nutrient intake in children with spinal muscular atrophy. MethodsWe performed a retrospective medical record review of prospectively collected data from children with spinal muscular atrophy followed at a multidisciplinary clinic at a tertiary referral center. We collected data including clinical parameters; anthropometrics, including weight, height, and body mass index (BMI); and 24-hour dietary intake records in all children followed in the clinic. Available data were found in records from the dietitian as part of a standard evaluation process, and additional clinical data were acquired from patient medical records. Subjects were classified based on spinal muscular atrophy type, and nutritional intake data were compared with dietary reference intakes for gender and age. Z-scores were calculated for weight for age (WAZ), height for age, and BMI (BMIZ) using the World Health Organization AnthroPlus software with appropriate World Health Organization reference growth standards. Subjects were classified as malnourished if their WAZ was <−2 or >+2. Anthropometric measurements were obtained at first visit and at a follow-up visit at an average of a 3-year interval between the clinic visits. A decline of more than 0.5 WAZ over this period was defined a priori as significant nutritional deterioration. ResultsWe analyzed data from 60 subjects, 26 (43%) female, with median age 5.5 years (interquartile range 2 years to 12 years). The cohort consisted of children with spinal muscular atrophy type 1 (28 %), type 2 (45 %), and type 3 (27 %). At the first clinic visit, nine (15%) patients were malnourished. Thirteen (23%) subjects had a significant decline in WAZ from −0.35 (−1.31 to 0.58) to −1.04 (−2.15 to 0.02) at follow-up after approximately 3 years. A third of these subjects were already malnourished at first visit. A significant decline in BMIZ was noted in 47% of the cohort, and the prevalence of severe malnutrition (BMIZ < −3) increased from 2% to 17% after 3 years. In children receiving specialized enteral nutrition via a feeding tube, overfeeding was recorded in 29% and underfeeding was recorded in 35%. Suboptimal vitamin D intake was recorded in 35% of patients with enteral feeding device. ConclusionsMalnutrition was prevalent in children with spinal muscular atrophy, and nearly half the cohort demonstrated nutritional deterioration over time. Energy, protein, and vitamin D intakes were inadequate in a majority of the cohort. Underfeeding was highly prevalent, but overfeeding was also present in a third of the enterally fed cohort. Future studies describing optimal nutrient requirements and body composition variables in this group are required.

Body composition of patients with Duchenne muscular dystrophy: the Greek experience

Cross-sectional study of steroid-dependent DMD subjects, who underwent dual-energy X-ray absorptiometry and laboratory metabolic bone profile evaluation. Forty-two patients and thirty-one controls were studied. Overall, DMD subjects were shorter (height Z-score=-1.4, p=0.01). Their bone mineral density (BMD) was low (lumbar spine BMD Z-score=-1.2, p<0.01, subcranial total body BMD Z-score=-1.8, p<0.01). Lean tissue mass (LTM) was also decreased (LTM Z-score=-2.2, p<0.01). The above findings were more pronounced in adolescence. Regarding adiposity, increased fat mass (FM) was found only in pubertal DMD patients (FM Z-score=1.4, p<0.01), whereas prepubertal, able-bodied patients did not differ from controls, thus confirming the initial hypothesis. Finally, 65% of DMD subjects had increased bone resorption markers and 57% had suboptimal vitamin D levels. The importance of using native population as controls for body composition analysis is highlighted. In Greece, abnormal body composition in DMD patients is more striking when loss of ambulation occurs and not during the prepubertal period, due to the concurrent presence of obesity in the pediatric population. Thus, adolescents with this neuromuscular disorder should be targeted toward prompt lifestyle interventions.

Vitamin D status is inversely associated with anemia and serum erythropoietin during pregnancy

Vitamin D and iron deficiencies frequently co-exist. It is now appreciated that mechanistic interactions between iron and vitamin D metabolism may underlie these associations. We examined interrelations between iron and vitamin D status and their regulatory hormones in pregnant adolescents, who are a group at risk of both suboptimal vitamin D and suboptimal iron status. The trial was a prospective longitudinal study of 158 pregnant adolescents (aged ≤18 y). Maternal circulating biomarkers of vitamin D and iron were determined at midgestation (∼25 wk) and delivery (∼40 wk). Linear regression was used to assess associations between vitamin D and iron status indicators. Bivariate and multivariate logistic regressions were used to generate the OR of anemia as a function of vitamin D status. A mediation analysis was performed to examine direct and indirect relations between vitamin D status, hemoglobin, and erythropoietin in maternal serum. Maternal 25-hydroxyvitamin D [25(OH)D] was positively associated with maternal hemoglobin at both midgestation and at delivery (P < 0.01 for both). After adjustment for age at enrollment and race, the odds of anemia at delivery was 8 times greater in adolescents with delivery 25(OH)D concentrations <50 nmol/L than in those with 25(OH)D concentrations ≥50 nmol/L (P <0.001). Maternal 25(OH)D was inversely associated with erythropoietin at both midgestation (P <0.05) and delivery (P <0.001). The significant relation observed between 25(OH)D and hemoglobin could be explained by a direct relation between 25(OH)D and hemoglobin and an indirect relation that was mediated by erythropoietin. In this group of pregnant adolescents, suboptimal vitamin D status was associated with increased risk of iron insufficiency and vice versa. These findings emphasize the need for screening for multiple nutrient deficiencies during pregnancy and greater attention to overlapping metabolic pathways when selecting prenatal supplementation regimens.