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Lack of Effect of Graded Doses of Vitamin D on Bone Metabolism of Breastfed Infants.

ABSTRACT: Objective:A range of doses of supplemental vitamin D has been shown to be effective in preventing rickets in breastfed infants, but the effect of different doses of vitamin D on bone metabolism and mineral content has not been delineated. Methods:In a randomized trial, breastfed infants received from 2 to 9 months daily supplements of vitamin D in doses of 200 IU/d, 400 IU/d, 600 IU/d or 800 IU/d. Measures of bone metabolism (plasma) were determined periodically and bone mineral content (DXA) was determined at study entry and at the end of winter when infants were 5.5 to 9 months old. The main findings have been reported; here we report findings related to bone metabolism. Results:There were no consistent meaningful effects of vitamin D dose on markers of bone metabolism. Some markers showed changes with age. Bone mineral content increased with age but showed no effect of vitamin D dose. Conclusion:Vitamin D in daily doses from 200 IU/d to 800 IU/d had no measurable effect on bone mineral content or bone metabolism of breastfed infants.

SUBMITTER: Ziegler EE

PROVIDER: S-EPMC5744599 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Lack of Effect of Graded Doses of Vitamin D on Bone Metabolism of Breastfed Infants.

Ziegler Ekhard E EE Koo Winston Wk WW Nelson Steven E SE Jeter Janice M JM

Journal of clinical nutrition and metabolism 20170927 1

<h4>Objective</h4>A range of doses of supplemental vitamin D has been shown to be effective in preventing rickets in breastfed infants, but the effect of different doses of vitamin D on bone metabolism and mineral content has not been delineated.<h4>Methods</h4>In a randomized trial, breastfed infants received from 2 to 9 months daily supplements of vitamin D in doses of 200 IU/d, 400 IU/d, 600 IU/d or 800 IU/d. Measures of bone metabolism (plasma) were determined periodically and bone mineral c ...[more]

PMID: 29293697

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Project description:Daily oral vitamin D supplementation (400 IU) is recommended for breastfeeding infants (≤1 y). Recent studies have examined alternative approaches to preventing vitamin D deficiency in this population. This systematic review and meta-analysis aimed to estimate the effects of maternal postpartum (M-PP) or infant intermittent (I-INT) vitamin D supplementation on infant 25-hydroxyvitamin D [25(OH)D] concentrations in comparison to routine direct infant daily (I-D) oral supplementation (400 IU). MEDLINE, MEDLINE In-Process, Embase, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched up to December 2018. Inclusion criteria consisted of published, peer-reviewed, vitamin D intervention trials involving lactating women and/or exclusively or partially breastfed term infants. Two reviewers independently extracted study characteristics (e.g., sample size, intervention dose, and duration and mode of administration) and related biochemical and clinical outcomes. Of 28 included trials, 5 randomized controlled trials were incorporated in meta-analyses examining infant 25(OH)D. Overall, M-PP supplementation resulted in modestly lower infant 25(OH)D compared with I-D supplementation (weighted mean difference = -8.1 nmol/L; 95% CI: -15.4, -0.9; I2 = 45%; P = 0.14; 3 trials), but the 2 most recent trials found M-PP to achieve similar infant 25(OH)D as I-D. Comparison of I-INT with I-D was confined to 2 trials with contradictory findings, and it was considered inappropriate for pooled analysis. Meta-analysis was therefore limited by a small number of eligible trials with variable quality of analytically derived 25(OH)D data and inconsistent reporting of safety outcomes, including effects on calcium homeostasis. Considering all 28 included trials, this systematic review highlights M-PP and I-INT regimens as plausible substitutes for routine daily infant vitamin D supplementation, but evidence remains too weak to support a policy update. Dose-ranging, adequately powered trials are required to establish the efficacy, safety, and feasibility of alternative strategies to prevent vitamin D deficiency in breastfeeding infants. This review was registered with PROSPERO as CRD42017069905.

Project description:BackgroundMice lacking vitamin D receptor (VDR) exhibit a glycogen storage disorder, disrupting carbohydrate utilization in muscle. Here, we asked if the defective carbohydrate metabolism alters the fat utilization by the skeletal muscles of vdr-/- mice.MethodsTo check the effect of high-fat-containing diets on muscle mass and metabolism of vdr-/- mice, we subjected them to two different milk fat-based diets (milk fat diet with 60% of energy from milk fat and milk-based diet [MBD] with 37% of energy from milk fat) and lard-based high-fat diet (HFD) containing 60% of energy from lard fat. Skeletal muscles and pancreas from these mice were analysed using RNA sequencing, quantitative reverse transcription polymerase chain reaction and western blot to understand the changes in signalling and metabolic pathways. Microscopic analyses of cryosections stained with haematoxylin and eosin, BODIPY, succinate dehydrogenase and periodic acid-Schiff reagent were performed to understand changes in morphology and metabolism of muscle fibres and pancreatic islets.ResultsTranscriptomic analyses showed that the skeletal muscles of vdr-/- mice exhibit upregulation of the fatty acid oxidation pathways, suggesting a shift towards increased lipid utilization even in a carbohydrate-enriched regular chow diet (chow). Two different milk fat-enriched diets restored body weight (12.01 ± 0.33 g in chow vs. 17.99 ± 0.62 g in MBD) and muscle weights (38.58 ± 3.84 mg in chow vs. 110.72 ± 1.96 mg in MBD for gastrocnemius [GAS]) of vdr-/- mice. Muscle ATP levels (0.56 ± 0.18 μmol in chow vs. 1.48 ± 0.08 μmol in MBD) and protein synthesis (0.25 ± 0.04 A.U. in chow vs. 2.02 ± 0.06 A.U. in MBD) were upregulated by MBD. However, despite increasing muscle energy levels, HFD failed to restore the muscle mass and cross-sectional area to that of wild-type (WT) mice (104.95 ± 2.6 mg for WT mice on chow vs. 77.26 ± 1.7 mg for vdr-/- mice on HFD for GAS). Moreover, HFD disrupted glucose homeostasis in vdr-/- mice, while MBD restored it. We further analysed insulin response and pancreatic insulin levels of these mice to show that HFD led to reduced insulin levels in pancreatic beta cells of vdr-/- mice (mean intensity of 1.5 × 10-8 for WT mice on chow vs. 4.3 × 10-9 for vdr-/- mice on HFD). At the same time, MBD restored glucose-stimulated pancreatic insulin response (mean intensity of 9.2 × 10-9 ).ConclusionsSkeletal muscles of vdr-/- mice are predisposed to utilize fatty acids as their primary energy source to circumvent their defective carbohydrate utilization. Thus, HFDs could restore energy levels in the skeletal muscles of vdr-/- mice. This study reveals that when mice are subjected to a lard-based HFD, VDR signalling is essential for maintaining insulin levels in pancreatic islets. Our data show a critical role of VDR in muscle metabolic flexibility and pancreatic insulin response.

Project description:BackgroundMost pregnant or lactating women in Canada will not meet iodine requirements without iodine supplementation.ObjectivesTo assess the iodine status of 132 mother-infant pairs based on secondary analyses of a vitamin D supplementation trial in breastfed infants from Montréal, Canada.MethodsMaternal iodine status was assessed using the breastmilk iodine concentration (BMIC). Singleton, term-born infants were studied from 1-36 months of age. Usual (adjusted for within-person variation) iodine intakes were estimated from urinary iodine and creatinine concentrations. Iodine status was assessed using median urinary iodine concentrations (UICs) and by estimating inadequate intakes by the cut-point method using a proposed Estimated Average Requirement for infants 0-6 months of age (72 μg/d).ResultsAt 1, 3, and 6 months of age, 70%, 63%, and 3% of infants, respectively, were exclusively breastfed. From 1-36 months of age (n = 82-129), the median UICs were ≥100 μg/L (range, 246-403 μg/L), which is the cutoff for adequate intakes set by the WHO for children <2 years. Almost all (98%-99%) infants at 1 and 2 months, 2 and 3 months, and 3 and 6 months of age had usual creatinine-adjusted iodine intakes ≥ 72 μg/d. The median BMIC was higher (P < 0.001) at 1 month compared to 6 months of lactation [1 month, 198 μg/kg (IQR, 124-274; n = 105) and 6 months, 109 μg/kg (IQR, 67-168; n = 78)]. At 1 and 6 months, 96% and 79% of mothers, respectively, had a BMIC ≥ 60 μg/kg, the lower limit of a normal reference range. The percentages of mothers that used a multivitamin-mineral (MVM) supplement containing iodine were 90% in pregnancy and 79% and 59% at 1 and 6 months of lactation, respectively.ConclusionsThe iodine status of infants was adequate throughout infancy. These results support a recommendation that all women who could become pregnant, who are pregnant, or who are breastfeeding take a daily MVM supplement containing iodine.

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Lack of Effect of Graded Doses of Vitamin D on Bone Metabolism of Breastfed Infants.

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Lack of Effect of Graded Doses of Vitamin D on Bone Metabolism of Breastfed Infants.

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