Safety and Efficacy of Early Vitamin D Supplementation in Critically Ill Extremely Preterm Infants: An Ancillary Study of a Randomized Trial

BackgroundDespite substantial evidence that vitamin D deficiency is highly prevalent among infants born extremely preterm (≤28 weeks’ of gestation), several consensus statements do not recommend vitamin D doses >400 IU/day for these infants. Safety remains a concern.ObjectiveThe study aim was to determine safety and efficacy profiles of enteral vitamin D in Black and White infants randomized to three different vitamin D doses soon after birth.DesignAncillary study of a masked randomized clinical trial.Participants/settingSeventy-three infants born extremely preterm between 2012 and 2015 at a southern US academic neonatal unit (33’ latitude) who had >90% compliance with the assigned intervention were included.InterventionInfants were randomized to receive placebo (placebo group), 200 IU/day vitamin D (200 IU group), or 800 IU/day vitamin D (800 IU group) during the first 28 days after birth.Main outcome measuresSafety outcomes included serum 25-hydroxy vitamin D (25[OH]D) and calcium concentrations. Efficacy outcomes included the predictive risk of bronchopulmonary dysplasia.Statistical analysisPer-protocol analysis using unadjusted, repeated-measures mixed models.ResultsMean birth weight was 815 ± 199 g. Half were male and 56% were Black. Of 58 infants with 25(OH)D measurements at birth, 40 (69%) had vitamin D deficiency (<20 ng/mL). The mean difference in 25(OH)D in nanograms per milliliter between Postnatal Day 28 and Postnatal Day 1 was +9 in the placebo group, +23 in the 200 IU group, and +62 in the 800 IU group (P < 0.0001). The increase observed in 25(OH)D was more significant among Black infants. The predictive risk of severe bronchopulmonary dysplasia in the 200 IU and 800 IU groups was lower, but this difference did not reach statistical significance. No vitamin D or calcium toxicity was observed.ConclusionsA vitamin D dose of 800 IU/day safely corrected vitamin D deficiency by Postnatal Day 14.     

The Importance of Dose,Frequency and Duration of Vitamin D Supplementation for Plasma 25-Hydroxyvitamin D

The importance of dose, frequency and duration of vitamin D supplementation for plasma 25(OH)D levels is not well described and rarely reported for supplementation that exceeds 2000 IU per day. The objective is to examine dose, frequency and duration of supplementation in relation to plasma 25(OH)D in a large population-based sample. We accessed data on 2714 volunteers that contributed to 4224 visits and applied multilevel regression. Compared to not using supplements, a minimum regimen of 1000–2000 IU once or twice per week for one month was not effective in raising 25(OH)D. Compared to this minimum regimen, higher doses of 2000–3000, 3000–4000, and 5000 IU or more were associated with a 7.49, 13.19 and 30.22 nmol/L 25(OH)D increase, respectively; frequencies of three to four, five to six and seven times/week were associated with a 5.44, 16.52 and 30.69 nmol/L increase, respectively; and supplementation of five months or longer was associated with an increase of 6.68 nmol/L (p < 0.01 for all). Age, body weight, physical activity, smoking, and self-rated health were significantly associated with 25(OH)D. Whereas dose, frequency and duration of supplementation are important to healthy subjects committed to optimizing their nutritional status, to the design of clinical trials, individual characteristics and lifestyle contribute substantially to 25(OH)D.     

Pharmacokinetics of High-Dose Weekly Oral Vitamin D3 Supplementation during the Third Trimester of Pregnancy in Dhaka,Bangladesh

A pharmacokinetic study was conducted to assess the biochemical dose-response and tolerability of high-dose prenatal vitamin D3 supplementation in Dhaka, Bangladesh (23°N). Pregnant women at 27–30 weeks gestation (n = 28) were randomized to 70,000 IU once + 35,000 IU/week vitamin D3 (group PH: pregnant, higher dose) or 14,000 IU/week vitamin D3 (PL: pregnant, lower dose) until delivery. A group of non-pregnant women (n = 16) was similarly administered 70,000 IU once + 35,000 IU/week for 10 weeks (NH: non-pregnant, higher-dose). Rise (∆) in serum 25-hydroxyvitamin D concentration ([25(OH)D]) above baseline was the primary pharmacokinetic outcome. Baseline mean [25(OH)D] were similar in PH and PL (35 nmol/L vs. 31 nmol/L, p = 0.34). A dose-response effect was observed: ∆[25(OH)D] at modeled steady-state was 19 nmol/L (95% CI, 1 to 37) higher in PH vs. PL (p = 0.044). ∆[25(OH)D] at modeled steady-state was lower in PH versus NH but the difference was not significant (−15 nmol/L, 95% CI −34 to 5; p = 0.13). In PH, 100% attained [25(OH)D] ≥ 50 nmol/L and 90% attained [25(OH)D] ≥ 80 nmol/L; in PL, 89% attained [25(OH)D] ≥ 50 nmol/L but 56% attained [25(OH)D] ≥ 80 nmol/L. Cord [25(OH)D] (n = 23) was slightly higher in PH versus PL (117 nmol/L vs. 98 nmol/L; p = 0.07). Vitamin D3 was well tolerated; there were no supplement-related serious adverse clinical events or hypercalcemia. In summary, a regimen of an initial dose of 70,000 IU and 35,000 IU/week vitamin D3 in the third trimester of pregnancy was non-hypercalcemic and attained [25(OH)D] ≥ 80 nmol/L in virtually all mothers and newborns. Further research is required to establish the safety of high-dose vitamin D3 in pregnancy and to determine if supplement-induced [25(OH)D] elevations lead to maternal-infant health benefits.     

Effects of Vitamin D3 Supplementation and Resistance Training on 25-Hydroxyvitamin D Status and Functional Performance of Older Adults: A Randomized Placebo-Controlled Trial

Vitamin D status is associated with muscle strength and performance in older adults. To examine the additive effects of vitamin D3 supplementation during resistance training, 100 seniors (65–85 years) participated in a 16-week intervention. Besides a daily dose of 400 mg of calcium, participants received either 800 IU vitamin D3 per day (VDD), 50,000 IU vitamin D3 per month (VDM) or nothing (CON). After the initial loading phase of four weeks, all groups started a 10-week resistance training program. Assessments of 25-hydroxyvitamin D (25(OH)D) status, muscle strength endurance (30-s chair stand and arm curl tests), aerobic capacity (6-min walk test) and functional mobility (gait speed and timed up and go test) were undertaken at baseline, after four weeks and at the end of the study. 25(OH)D status significantly improved in VDD and VDM, but not in CON (time x group: p = 0.021), as 15.2% of CON, 40.0% of VDD and 61.1% of VDM reached vitamin D sufficiency (>30 ng/mL; p = 0.004). Chair stand test, arm curl test, 6-min walk test, gait speed and timed up and go test improved over the whole intervention period (p < 0.05), however only chair stand and arm curl test were selectively affected by resistance training (p < 0.001). Neither muscle strength endurance, nor functional mobility or aerobic capacity were modulated by vitamin D supplementation. Therefore, the mere amelioration of 25(OH)D status of older adults does not lead to an additive effect on muscular performance during RT.     

Vitamin D Status and Factors Associated with Vitamin D Deficiency during the First Year of Life in Preterm Infants

We aimed to investigate the changes in vitamin D levels and factors associated with vitamin D deficiency (VDD) during the first year of life in Korean preterm infants. We enrolled 333 preterm infants who were born at Kyungpook National University Children’s Hospital between March 2013 and December 2019. 25-hydroxyvitamin D (25-OHD) levels and medical records were collected at birth, 6 months, and 12 months of age. The mean gestational age was 33.4 ± 2.3 weeks and mean 25-OHD levels at birth were 18.2 ± 13.5 ng/mL. The incidence of VDD was 82.8%, 30.6%, and 27.0% at birth, 6 months, and 12 months, respectively. The incidence of severe VDD (25-OHD < 10 ng/mL) was 31.5%, 1.5%, and 0%, at birth, 6 months, and 12 months, respectively. Among infants with severe VDD, the deficiency persisted in 49.6% at 6 months, and 35.3% at 12 months. The strongest predictor of VDD during follow-up was 25-OHD concentration at birth. Vitamin D supplementation at 400 IU/day did not affect vitamin D levels during the first year of life. Therefore, it is important to prevent neonatal VDD through maternal vitamin D supplementation during pregnancy. Further research is needed to determine the optimal vitamin D supplementation dose for Korean preterm infants.     

Evaluating the Evidence in Clinical Studies of Vitamin D in COVID-19

Laboratory evidence provides a biological rationale for the benefits of vitamin D in COVID-19, and vitamin D supplementation is associated with reduced risk of respiratory infections. Most of the clinical studies of vitamin D in COVID-19 have been observational, and the most serious problem with observational study design is that of confounding. Observational studies typically assess the relationship of 25(OH)D values with COVID-19 outcomes. Many conditions associated with low vitamin D status are also associated with worse COVID-19 outcomes. Randomized controlled trials (RCTs) overcome the problem of confounding, typically comparing outcomes between groups receiving vitamin D supplementation or placebo. However, any benefit of vitamin D in COVID-19 may be related to the dose, duration, daily vs. bolus administration, interaction with other treatments, and timing of administration prior to or during the illness. Serum 25(OH)D values >50 nmol/L have been associated with reduced infection rates, severity of COVID-19, and mortality in observational studies. Few RCTs of vitamin D supplementation have been completed, and they have shown no benefit of vitamin D in hospitalized patients. Vitamin D may benefit those with mild or asymptomatic COVID-19, and those with greater 25(OH)D values may have lower risk of acquiring infection. Because those at greatest risk of COVID-19 are also at greatest risk of vitamin D deficiency, it is reasonable to recommend vitamin D supplementation 15–20 mcg (600–800 IU) daily for the general population during the COVID-19 pandemic. Vitamin D doses greater than 100 mcg (4000 IU) daily should not be used without monitoring serum 25(OH)D and calcium.     

Effects of Vitamin D Supplementation on 24-Hour Blood Pressure in Patients with Low 25-Hydroxyvitamin D Levels: A Randomized Controlled Trial

Accumulating evidence suggests that potential cardiovascular benefits of vitamin D supplementation may be restricted to individuals with very low 25-hydroxyvitamin D (25(OH)D) concentrations; the effect of vitamin D on blood pressure (BP) remains unclear. We addressed this issue in a post hoc analysis of the double-blind, randomized, placebo-controlled Styrian Vitamin D Hypertension Trial (2011–2014) with 200 hypertensive patients with 25(OH)D levels <30 ng/mL. We evaluated whether 2800 IU of vitamin D3/day or placebo (1:1) for 8 weeks affects 24-hour systolic ambulatory BP in patients with 25(OH)D concentrations <20 ng/mL, <16 ng/mL, and <12 ng/mL and whether achieved 25(OH)D concentrations were associated with BP measures. Taking into account correction for multiple testing, p values < 0.0026 were considered significant. No significant treatment effects on 24-hour BP were observed when different baseline 25(OH)D thresholds were used (all p-values > 0.30). However, there was a marginally significant trend towards an inverse association between the achieved 25(OH)D level with 24-hour systolic BP (−0.196 per ng/mL 25(OH)D, 95% CI (−0.325 to −0.067); p = 0.003). In conclusion, we could not document the antihypertensive effects of vitamin D in vitamin D-deficient individuals, but the association between achieved 25(OH)D concentrations and BP warrants further investigations on cardiovascular benefits of vitamin D in severe vitamin D deficiency.     

Prevalence and Correlates of Vitamin D Deficiency among Young South African Infants: A Birth Cohort Study

Early-life vitamin D deficiency is associated with adverse child health outcomes, but the prevalence of vitamin D deficiency and its correlates in infants remains underexplored, particularly in sub-Saharan Africa. We aimed to investigate the prevalence of vitamin D deficiency and its correlates among young infants in South Africa. This study included 744 infants, aged 6–10 weeks from the Drakenstein Child Health Study, a population-based birth cohort. Infants were categorized into distinct categories based on serum 25(OH)D concentration level including deficient (<50 nmol/L), insufficient (50–74 nmol/L), and sufficient (≥75 nmol/L). Using multivariable Tobit and logistic regression models, we examined the correlates of serum 25(OH)D₃ levels. The overall prevalence of vitamin D deficiency was 81% (95% confidence intervals (CI]) 78–83). Multivariable regression analysis showed that serum 25(OH)D₃ concentration was independently associated with study site, socioeconomic status, and sex. Birth in winter and breastfeeding were the strongest predictors of lower serum 25(OH)D₃ concentration levels. Compared to non-breastfed children, children breastfed were at higher risk of vitamin D deficiency (AOR, 1.96; 95% CI, 1.04–3.67) and breastfeeding for more than one month was associated with greater likelihood of vitamin D deficiency (AOR, 5.40; 95% CI, 2.37–12.32) and lower vitamin D concentrations (−16.22 nmol/L; 95% CI, −21.06, −11.39). Vitamin D deficiency in infants is ubiquitous, under-recognised, and strongly associated with season of birth and breastfeeding in this setting. Nutritional interventions with vitamin D supplementation in national health programs in low- and middle-income countries are urgently needed to improve early-life vitamin D status in infants.     

Pharmacodynamics of Oral Cholecalciferol in Healthy Individuals with Vitamin D Deficiency: A Randomized Open-Label Study

Comparative pharmacodynamic (PD) analyses on different dosing schedules for cholecalciferol supplementation are limited. This was an open-label, randomized, parallel-group study involving 75 healthy individuals deficient in vitamin D (baseline 25OHD < 20 ng/mL) receiving oral cholecalciferol with three different dosing regimens: Group A: 10,000 IU/day for 8 weeks followed by 1000 IU/day for 4 weeks; Group B: 50,000 IU/week for 12 weeks and Group C: 100,000 IU every other week for 12 weeks. Regulators of calcium and phosphate homeostasis, bone turnover markers and Wnt inhibitors were measured at baseline, Day 28, 53, 84, and 112. The 1,25OH2D increased at each time point. The increase was greater (p < 0.05) for group A vs. B and C at Day 28, and vs. group B at Day 56. No significant difference among groups was observed for the other biomarkers. The 24,25OH2D remained stable over time. PTH decreased at Day 84 and FGF-23 increased at all time points. CTX-I and PINP increased slightly at Day 28. BALP decreased from Day 56 onward. Dkk-1 increased from Day 56 onward, while sclerostin did not show significant changes. In healthy individuals deficient in vitamin D, vitamin D supplementation exerted effects on multiple regulators of calcium, phosphate and bone metabolism, without marked differences using the three regimens.     

不同剂量维生素D补充在早产儿中的应用研究

目的 评估不同剂量维生素D补充对胎龄≤34周早产儿出院时维生素D水平的影响,为早产儿生后合理补充维生素D提供依据。方法 选择2019年1月—2020年6月在博罗县妇幼保健计划生育服务中心出生的胎龄≤34周早产儿67例,在完全肠内喂养后开始口服维生素D,并随机分为维生素D低剂量组(n=32)和高剂量组(n=35),比较两组患儿出院时25(OH)D水平、维生素D缺乏/不足的比例及相关不良反应发生率。结果 两组患儿出生时脐带血25(OH)D水平、维生素D缺乏/不足发生率比较,差异无统计学意义(P＞0.05);出院时高剂量组血清25(OH)D水平明显高于低剂量组、维生素D缺乏/不足发生率明显低于低剂量组(t=2.872、χ²=4.189,P＜0.05),但高剂量组出院时维生素D缺乏/不足发生率仍为28.6%。结论 对于胎龄≤34周的早产儿,给予补充维生素D 800 U/d可明显改善患儿出院时维生素D缺乏或不足的情况,但对于胎龄更小、出生体重更低的超低出生体重儿,可能需要更大剂量的维生素D补充。     

Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety

For adults, the 5-microg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension. Total-body sun exposure easily provides the equivalent of 250 microg (10000 IU) vitamin D/d, suggesting that this is a physiologic limit. Sailors in US submarines are deprived of environmentally acquired vitamin D equivalent to 20-50 microg (800-2000 IU)/d. The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 microg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 microg (4000 IU)/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 microg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of > or = 1000 microg (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 microg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 microg (2000 IU)/d is too low by at least 5-fold.     

无锡市足月新生儿维生素D水平及适宜补充剂量的研究

目的 分析无锡市新生儿维生素D(VD)的营养状况及其影响因素,为制定适合本地区的新生儿VD补充方案提供科学依据。方法 选取2015年3月-2018年3月入住无锡市人民医院新生儿科的足月、母乳喂养、日龄≤7 d的新生儿347例,检测其血清25-(OH)D基础水平,其中血清25-(OH)D≤50 nmol/L的新生儿随机分为两组,分别给予400 U/d或800 U/d VD口服,6周后复查。同时对其母亲一般信息及孕期补充VD情况等展开问卷调查。结果 VD缺乏、VD不足和VD充足的比例分别为91.07%、8.07%和0.86%。夏秋季出生的患儿血清25-(OH)D水平较冬春季出生的患儿高(t=-3.467,P<0.05)。6周后复查发现,总体患儿血清25-(OH)D平均值较前上升,VD缺乏者比例下降(χ²=118.235、163.196,P＜0.05)。 新生儿血清25-(OH)D水平与母亲孕期是否补充充足的钙剂、VD存在一定的相关性(r=0.116,P=0.043)。结论 无锡地区足月新生儿VD普遍缺乏,建议根据母亲孕期VD补充情况,可以将早期足月新生儿VD补充剂量调整为400~800 U/d,持续6周。     

Applying Machine Learning to Determine 25(OH)D Threshold Levels Using Data from the AMATERASU Vitamin D Supplementation Trial in Patients with Digestive Tract Cancer

Some controversy remains on thresholds for deficiency or sufficiency of serum 25-hydroxyvitamin D (25(OH)D) levels. Moreover, 25(OH)D levels sufficient for bone health might differ from those required for cancer survival. This study aimed to explore these 25(OH)D threshold levels by applying the machine learning method of multivariable adaptive regression splines (MARS) in post hoc analyses using data from the AMATERASU trial, which randomly assigned Japanese patients with digestive tract cancer to receive vitamin D or placebo supplementation. Using MARS, threshold 25(OH)D levels were estimated as 17 ng/mL for calcium and 29 ng/mL for parathyroid hormone (PTH). Vitamin D supplementation increased calcium levels in patients with baseline 25(OH)D levels ≤17 ng/mL, suggesting deficiency for bone health, but not in those >17 ng/mL. Vitamin D supplementation improved 5-year relapse-free survival (RFS) compared with placebo in patients with intermediate 25(OH)D levels (18–28 ng/mL): vitamin D, 84% vs. placebo, 71%; hazard ratio, 0.49; 95% confidence interval, 0.25–0.96; p = 0.04. In contrast, vitamin D supplementation did not improve 5-year RFS among patients with low (≤17 ng/mL) or with high (≥29 ng/mL) 25(OH)D levels. MARS might be a reliable method with the potential to eliminate guesswork in the estimation of threshold values of biomarkers.     

A Randomized,Double-Blind,Parallel Study to Evaluate the Dose-Response of Three Different Vitamin D Treatment Schemes on the 25-Hydroxyvitamin D Serum Concentration in Patients with Vitamin D Deficiency

Many people worldwide are vitamin D (VTD) deficient or insufficient, and there is still no consensus on the dose of VTD that should be administered to achieve a 25(OH)D concentration of 20 or 30 ng/mL. In this study, we aimed to determine an adapted supplementation of VTD able to quickly and safely increase the vitamin D status of healthy adults with low 25(OH)D. One hundred and fifty (150) subjects were randomized into three groups, each to receive, orally, a loading dose of 50,000, 100,000 or 200,000 IU of VTD3 at Week 0, followed by 25,000, 50,000 or 100,000 IU at Week 4 and Week 8. Whereas 25(OH)D baseline values were not different between groups (p = 0.42), a significant increase was observed at Week 12 (p < 0.0001) with a mean change from baseline of 7.72 ± 5.08, 13.3 ± 5.88 and 20.12 ± 7.79 ng/mL. A plateau was reached after eight weeks. No related adverse event was recorded. This study demonstrated a linear dose-response relationship with an increase in 25(OH)D levels proportional to the dose administered. In conclusion, a loading dose of 200,000 IU VTD3 followed by a monthly dose of 100,000 IU is the best dosing schedule to quickly and safely correct the VTD status.     

Vitamin D Intake and Status in 6-Year-Old Icelandic Children Followed up from Infancy

High serum 25-hydroxyvitamin D (25(OH)D) levels have been observed in infants in Nordic countries, likely due to vitamin D supplement use. Internationally, little is known about tracking vitamin D status from infancy to childhood. Following up 1-year-old infants in our national longitudinal cohort, our aims were to study vitamin D intake and status in healthy 6-year-old Icelandic children (n = 139) and to track vitamin D status from one year of age. At six years, the mean 25(OH)D level was 56.5 nmol/L (SD 17.9) and 64% of children were vitamin D sufficient (25(OH)D ≥ 50 nmol/L). A logistic regression model adjusted for gender and breastfeeding showed that higher total vitamin D intake (Odds ratio (OR) = 1.27, 95% confidence interval (CI) = 1.08–1.49), blood samples collected in summer (OR = 8.88, 95% CI = 1.83–43.23) or autumn (OR = 5.64, 95% CI = 1.16–27.32) compared to winter/spring, and 25(OH)D at age one (OR = 1.02, 95% CI = 1.002–1.04) were independently associated with vitamin D sufficiency at age six. The correlation between 25(OH)D at age one and six was 0.34 (p = 0.003). Our findings suggest that vitamin D status in infancy, current vitamin D intake and season are predictors of vitamin D status in early school age children. Our finding of vitamin D status tracking from infancy to childhood provides motivation for further studies on tracking and its clinical significance.     

Vitamin D Intake and Status in 12-Month-Old Infants at 63–66° N

The objective was to assess the vitamin D status in healthy 12-month-old infants in relation to quantity and sources of dietary vitamin D, breastfeeding and seasons. Subjects were 76 12-month-old infants. Serum levels of 25-hydroxyvitamin D (25(OH)D) ≥ 50 nmol/L were considered indicative of vitamin D sufficiency and 25(OH)D < 27.5 nmol/L as being indicative of increased risk for rickets. Additionally, 25(OH)D > 125 nmol/L was considered possibly adversely high. Total vitamin D at 9–12 months (eight data collection days) included intake from diet and supplements. The mean ± SD of vitamin D intake was 8.8 ± 5.2 μg/day and serum 25(OH)D 98.1 ± 32.2 nmol/L (range 39.3–165.5). Ninety-two percent of infants were vitamin D sufficient and none at increased risk for rickets. The 26% infants using fortified products and supplements never/irregularly or in small amounts had lower 25(OH)D (76.8 ± 27.1 nmol/L) than the 22% using fortified products (100.0 ± 31.4 nmol/L), 18% using supplements (104.6 ± 37.0 nmol/L) and 33% using both (110.3 ± 26.6 nmol/L). Five of six infants with 25(OH)D < 50 nmol/L had no intake of supplements or fortified products from 0 to 12 months. Supplement use increased the odds of 25(OH)D > 125 nmol/L. Breastfeeding and season did not affect vitamin D status. The majority of infants were vitamin D sufficient. Our findings highlight the need for vitamin D supplements or fortified products all year round, regardless of breastfeeding.     

25-Hydroxyvitamin D and vitamin D in human milk: effects of supplementation and season

Breast-milk 25-hydroxyvitamin D (25-[OH]D) and vitamin D were measured in mothers supplemented with 2000 or 1000 IU (50 or 25 micrograms) of vitamin D/d or with no supplementation. Fore- and hindmilk samples were collected at two stages of lactation (8 and 15 or 20 wk after delivery) and at different seasons. Season affected the levels of 25-(OH)D and vitamin D. The 25-(OH)D levels were higher in hind- than in foremilk. Supplementation had no effect on vitamin D levels. Milk 25-(OH)D levels of mothers receiving either 1000 or 2000 IU (25 or 50 micrograms) vitamin D/d were significantly higher than those of unsupplemented mothers in February and April. In theory, supplementation with 2000 IU (50 micrograms) vitamin D should have increased the calculated antirachitic activity of the milk in winter to the levels of unsupplemented mothers in September; however, responses varied widely among individuals.     

A Randomized Clinical Trial of Vitamin D Supplementation in Healthy Adolescents

PurposeThe most safe and effective dose of vitamin D supplementation for healthy adolescents is currently unknown. The aim of this study was to compare the efficacy of 200 IU versus 1,000 IU of daily vitamin D₃ for supplementation in healthy adolescents with baseline vitamin D sufficiency.MethodsWe conducted a double-blind, randomized clinical trial. Fifty-six subjects, ages 11–19 years, with baseline vitamin D sufficiency received 1,000 IU or 200 IU of daily vitamin D₃ for 11 weeks. Compliance was assessed using MEMS6 Trackcaps and pill counts.ResultsFifty-three subjects completed the clinical trial. Subjects in the two treatment arms were similar in terms of age, race, gender, body mass index, and dietary calcium and vitamin D intake. Serum 25(OH)D level in the 200 IU treatment arm was 28.1 ± 6.2 ng/mL at baseline (mean ± SD) and 28.9 ± 7.0 ng/mL at follow-up. In the 1,000 IU treatment arm, 25(OH)D levels were 29.0 ± 7.3 and 30.1 ± 6.6 at baseline and follow-up, respectively. Mean change in 25(OH)D level did not differ significantly between treatment arms (p = .87), nor did mean change in parathyroid hormone, calcium, phosphate, bone turnover markers, fasting glucose, or fasting insulin.ConclusionsIn healthy adolescents with baseline vitamin D sufficiency, supplementation with vitamin D₃ doses of 200 and 1,000 IU for 11 weeks did not increase serum 25(OH)D levels, with no significant difference observed between treatment arms.