Doses Of Vitamin D3 Supplementation Research Articles

A Narrative Review on the Potential Role of Vitamin D3 in the Prevention, Protection, and Disease Mitigation of Acute and Long COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has challenged global health systems and economies from January 2020. COVID-19 caused by the infectious severe acute respiratory syndrome coronavirus (SARS-CoV-2) has acute respiratory and cardiometabolic symptoms that can be severe and lethal. Long-term physiological and psychological symptoms, known as long COVID-19, persist affecting multiple organ systems. While vaccinations support the fight against SARS-CoV-2, other effective mechanisms of population protection should exist given the presence of yet unvaccinated and at-risk vulnerable groups, global disease comorbidities, and short-lived vaccine responses. The review proposes vitamin D3 as a plausible molecule for prevention, protection, and disease mitigation of acute and long COVID-19. Epidemiological studies have shown that individuals who were deficient in vitamin D3 had worse COVID-19 health outcomes and mortality rates. Higher doses of vitamin D3 supplementation may improve health and survivorship in individuals of various age groups, comorbidities, and severity of disease symptoms. Vitamin D3's biological effects can provide protection and repair in multiple organ systems affected by SARS-CoV-2. Vitamin D3 supplementation can potentially support disease-mitigation in acute and long COVID-19.

Efficacy of ultraviolet B radiation versus vitamin D3 on postural control and cognitive functions in relapsing-remitting multiple sclerosis: A randomized controlled study

BackgroundThe relapsing-remitting multiple sclerosis (RRMS) is the most common type of MS with prevalence rate 20–60 patients/100.000 individuals in Egypt. Poor postural control and cognitive dysfunctions are well-established complications of RRMS without potent remedy yet. The latest evidence highlighted the potential and independent immune-modulating effects of vitamin D3 and ultraviolet radiation in the management of RRMS. ObjectiveTo investigate the efficacy of broadband ultraviolet B radiation (UVBR) versus moderate loading dose of vitamin D3 supplementation in improving postural control and cognitive functions. DesignPretest-posttest randomized controlled study. SettingMultiple sclerosis outpatient unit of Kasr Al-Ainy Hospital. ParticipantsForty-seven patients with RRMS were recruited from both genders, yet only 40 completed the study. InterventionsPatients were randomized into two groups: UVBR group involved 24 patients, received sessions for 4 weeks and vitamin D3 group involved 23 patients, took vitamin D3 supplementation (50 000 IU/week) for 12 weeks. Main outcome measuresOverall balance system index (OSI) and symbol digit modalities test (SDMT). ResultsHighly significant decrease (P < 0.001) of the OSI in both groups post-treatment, indicating improved postural control. Moreover, highly significant improvement in the SDMT scores was noted, indicating information processing speed enhancement. Nonetheless, no statistically significant (P ≥ 0.05) differences were evident between the two groups post-treatment in all tested measures. ConclusionBoth therapeutic programs were statistically equal in improving postural control and cognitive functions. However, clinically, UVBR therapy was more convenient owing to its shorter treatment time and higher percentage of change for all tested measures.

Abstract 49: The Effects of Vitamin D Supplementation on Subclinical Cardiovascular Disease: Results From the Sturdy Trial

Background: In observational studies, older adults with insufficient or deficient serum vitamin D levels are at higher risk of cardiovascular disease (CVD), but randomized trials have failed to demonstrate reduction in CVD risk from vitamin D supplementation. This is possibly because the doses of vitamin D supplements tested were too low. Objective: To determine if higher doses of vitamin D supplementation lower high sensitivity cardiac troponin level (hs-cTnI) and N-terminal pro b-type natriuretic peptide (NT-proBNP), markers of subclinical CVD. Methods: The Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a double-blind, randomized, response-adaptive trial that tested the effects of 4 doses of vitamin D3 supplementation (200, 1000, 2000, and 4000 IU/day) on fall risk in adults aged ≥70 years old with low serum 25-hydroxyvitamin D levels (10-29 ng/ml). Hs-cTnI and NT-proBNP levels were measured at baseline and at 3-, 12- and 24-month follow-up visits. For analysis, participants were divided into low (200 IU/day) and high dose (1000+ IU/day) vitamin D treatment groups. The effects of vitamin D dose on hs-cTnI and NT-proBNP were assessed via mixed effects tobit models. Results: Among 688 participants (mean age of 77 ± 5 years, 44% were women, and 18% were Black), 50.7% were in the high-dose treatment group (1000+ IU/day). Hs-cTnI increased in both the low and high dose groups by 5.1% and 5.8%, respectively; likewise, NT-proBNP increased in both groups by 11.3% and 9.3%, respectively ( Figure). Compared to the low-dose group, high-dose vitamin D treatment did not affect hs-cTnI (1.7 % difference; 95% CI: -5.3, 9.3) or NT-proBNP (-1.8 % difference; 95% CI: -9.3, 6.3). Conclusions: Compared to low dose vitamin D supplementation, a higher dose did not affect markers of subclinical CVD in older adults with low serum vitamin D levels. These findings do not support higher doses of vitamin D as an intervention to reduce the risk of CVD in this population.

Effect of a high vs. standard dose of vitamin D3 supplementation on bone metabolism and kidney function in children with chronic kidney disease.

We investigated the effects of high- vs. standard-dose vitamin D supplementation on kidney function and bone metabolism in children with chronic kidney disease (CKD). Children were randomized to receive one of two formulations: 75 participants received 2,000 IU/D of oral supplementation of vitamin D, while 75 participants received 400 IU/d for a minimum of 4 months. We investigated the effects of vitamin D supplementation on kidney-related indicators and bone metabolism-related indicators at different doses. A total of 158 participants were screened, among whom 150 met the inclusion criteria. The indicators of chronic kidney disease such as eGFR and serum uric acid were negatively correlated with the 25(OH)D level and BMD. Serum 25(OH)D and osteocalcin levels were positively correlated with spine BMD. The standard dose of vitamin D can improve the serum uric acid level, but high doses of vitamin D supplementation had no significant effect on the serum uric acid level. High doses of vitamin D supplementation can also improve the alkaline phosphatase level. When comparing the results of different doses of vitamin D supplementation, it was found that high-dose vitamin D supplementation did not improve bone density in the spine and femur neck relative to the standard dose of vitamin D but improved hypocalcemia and N-terminal propeptide of the human procollagen type I (PINP) level. Among the children with clinical kidney disease, high-dose vitamin D treatment for 4 months resulted in statistically significant improvement in kidney function but no significant difference in bone metabolism compared with the standard-dose vitamin D treatment.

Effects of Vitamin D on Physical Function: Results From the STURDY Trial.

Studies of the relationship between vitamin D and physical functioning have had inconsistent results. Physical functioning measures were collected for up to 2 years during a 2-stage, Bayesian, response-adaptive, randomized trial of 4 doses of vitamin D3 supplementation (200 [control], 1 000, 2 000, and 4 000 IU/day) to prevent falls. Two community-based research units enrolled adults aged ≥70 years, with elevated fall risk and serum 25-hydroxyvitamin D level of 10-29 ng/mL. The Pooled Higher Doses (PHD) group (≥1 000 IU/day, n = 349) was compared to the control group (n = 339) on changes in Short Physical Performance Battery (SPPB) score and its component tests, Timed Up-and-Go (TUG) test, 6-minute walk distance, and grip strength. The trial enrolled 688 participants. Mean age was 77.2 years, 56.4% were male, 79.7% White, and 18.2% Black. While the PHD and control groups both lost function over time on most outcomes, the 2 groups did not show differential change overall on any outcome. Incidence of transitioning to poor functioning on gait speed, SPPB score, or TUG test did not differ by dose group. In older persons with low serum 25-hydroxyvitamin D level and elevated fall risk, high-dose vitamin D supplementation, ≥1 000 IU/day, did not improve measures of physical function compared to 200 IU/day. NCT02166333.

Effects of Vitamin D Supplementation on Orthostatic Hypotension: Results From the STURDY Trial.

Vitamin D3 supplementation is considered a potential intervention to prevent orthostatic hypotension (OH) based on observational evidence that vitamin D levels are inversely associated with OH. With data from The Study to Understand Fall Reduction and Vitamin D in You (STURDY), a double-blind, randomized, response-adaptive trial, we determined if higher doses of vitamin D3 reduced risk of OH. STURDY tested the effects of higher (1,000+ IU/day, i.e., 1,000, 2,000, and 4,000 IU/day combined) vs. lower-dose vitamin D3 (200 IU/day, comparison) on fall risk in adults ages 70 years and older with low serum 25-hydroxyvitamin D (25(OH)D, 10-29 ng/ml). OH was determined at baseline, 3, 12, and 24 months by taking the difference between seated and standing blood pressure (BP). OH was defined as a drop in systolic or diastolic BP of at least 20 or 10 mm Hg after 1 minute of standing. Participants were also asked about OH symptoms during the assessment and the preceding month. Among 688 participants (mean age 77 [SD, 5] years; 44% women; 18% Black), the mean baseline systolic/diastolic BP was 130 (19)/67 (11) mm Hg, serum 25(OH)D was 22.1 (5.1) ng/ml, and 2.8% had OH. There were 2,136 OH assessments over the maximum 2-year follow-up period. Compared with 200 IU/day, 1,000+ IU/day was not associated with seated, standing, or orthostatic BP, and it did not lower risk of OH or orthostatic symptoms. These findings do not support use of higher doses of vitamin D3 supplementation as an intervention to prevent OH. Trial Number NCT02166333.

High-Dose Vitamin D Supplementation in Pregnancy and Neurodevelopment in Childhood

Observational studies have reported an association between high maternal vitamin D levels and improved neurodevelopment in offspring, but no randomized clinical trial (RCT) has investigated these observations. To determine whether high-dose vitamin D supplementation during pregnancy improves offspring neurodevelopment from birth to age 6 years. This prespecified secondary analysis of a double-blinded, placebo-controlled RCT of high-dose vitamin D3 supplementation vs standard dose during the third trimester of pregnancy was conducted in the unselected prospective mother-child birth cohort at a single-center research unit in Denmark as part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC-2010). Participants included pregnant women; women with vitamin D intake greater than 600 IU/d or an endocrine, heart, or kidney disorder, and those who did not speak Danish fluently were excluded. Neurodevelopmental assessments for offspring of these women were performed at ages 0 to 6 years. Children born prematurely (gestational week <37), with low birth weight (<2500 g), or with a neurological disease affecting neurodevelopment were excluded. Data were analyzed from August 2019 to February 2020. High-dose (ie, 2800 IU/d) vs standard dose (ie, 400 IU/d) vitamin D3 supplementation from pregnancy week 24 until 1 week after birth. The primary outcome of interest was cognitive development assessed at 2.5 years using the Bayley Scales of Infant and Toddler Development. Other neurodevelopmental outcomes included age of motor milestone achievement (Denver Developmental Index and World Health Organization milestone registration), language development (MacArthur-Bates Communicative Development Inventories), general neurodevelopment at age 3 years (Ages and Stages Questionnaire), and emotional and behavioral problems at age 6 years (Strengths and Difficulties Questionnaire). Among 623 women randomized, 315 were randomized to high-dose vitamin D3 and 308 were randomized to standard dose placebo. A total of 551 children were evaluated from birth to age 6 years, (282 [51.2%] boys; 528 [95.8%] White), with 277 children in the high-dose vitamin D3 group and 274 children in the standard dose group. There was no effect of the high-dose compared with standard dose of vitamin D3 supplementation during pregnancy on offspring achievement of motor milestones (β = 0.08 [95% CI, -0.26 to 0.43]; P = .64), cognitive development (score difference: 0.34 [95% CI, -1.32 to 1.99]; P = .70), general neurodevelopment (median [IQR] communication score: 50 [50-55] vs 50 [50-55]; P = .62), or emotional and behavioral problems (odds ratio, 0.76 [95% CI, 0.53 to 1.09]; P = .14). There was no effect on language development expressed by the word production at 1 year (median [IQR], 2 [0-6] words vs 3 [1-6] words; P = .16), although a decreased word production was apparent at 2 years in children in the high-dose vitamin D3 group (median [IQR], 232 [113-346] words vs 253 [149-382.5] words; P = .02). In this prespecified secondary analysis of an RCT, maternal high-dose vitamin D3 supplementation during the third trimester of pregnancy did not improve neurodevelopmental outcomes in the offspring during the first 6 years of life. These findings contribute essential information clarifying the effects of prenatal exposure to vitamin D on neurodevelopment in childhood. ClinicalTrials.gov Identifier: NCT00856947.

Effect of Vitamin D3 Supplementation on Glycated Albumin in Adults with Type 2 Diabetes

Abstract Objectives Albumin is the most abundant protein in serum with half-life of 2–3 weeks. Several studies suggested glycated albumin (GA) may provide a more accurate measure of extracellular glycation status, compared to hemoglobin A1C. Low serum vitamin D level [25(OH)D3] has been linked to diabetes. The aim of this study was to investigate the effect of different doses of vitamin D3 supplementation for 3 and 6 months on serum glycated albumin (GA) in individuals with type 2 diabetes (T2D) and hypovitaminosis D. Methods In this clinical trial, we assessed the effect of daily supplementation with 4000 and 6000 IU of vitamin D3 over 6 months on GA among 68 adults with T2D and hypovitaminosis D. Measurements of variables were conducted at baseline, 3 months and 6 months. Mixed model was used to compare treatment groups. Covariates in the adjusted model included age, gender, body mass index (BMI), sun exposure, fasting plasma glucose, insulin and C-reactive protein (CRP). Results After testing for normal distribution of variables, 65 participants, females (n = 40) and males (n = 25), were included in the analysis. Mean age was 54.52 ± 7.86 years. Mean serum 25(OH)D3 at baseline, 3 months and 6 months were 22.4 ± 6.77, 40.4 ± 13.68, and 40.57 ± 14.55, respectively. Mean GA at baseline, 3 months and 6 months were 4.69 ± 1.7, 4.13 ± 1.09, and 4.42 ± 1.23, respectively. Mixed model analysis controlling for interactions between 4000 IU and 6000 IU/day doses and outcome variables showed no differences between 2 treatment groups. Unadjusted pairwise comparisons between GA were a statistically significant from baseline to 3 months (P = 0.015), and from 3 months to 6 months (P = 0.039), but not from baseline to 6 months (P = 0.488). After adjusting for covariates, the model remained statistically significant for baseline and 3 months (P = 0.018) but not for 3 months to 6 month (P = 0.069), nor for baseline and 6 months (P = 0.471). Conclusions GA may be a more sensitive biomarker for oxidative/glycemic changes in individuals with T2D and hypovitaminosis D and daily supplementation with higher doses of vitamin D3 may have beneficial effects on their health status. Larger studies with longer durations among different racial and ethnic groups may help to confirm these findings. Funding Sources Funding for this research was provided through an NIH/NIDDK sponsored grant.

Obesity and efficacy of vitamin D3 supplementation in healthy black adults.

Results from recent clinical trials suggest that vitamin D efficacy against cancermay be influenced by body mass index. As suppression of parathyroid hormone (PTH) is one indicator of vitamin D efficacy, we examined to what extent doses of vitamin D3 supplementation suppress PTH levels in individuals with and without obesity. A total of 328 healthy African Americans were randomized into the following four groups and treated for 3months: placebo, 1,000, 2,000, or 4,000IU/day of vitamin D3 supplementation. Among the participants, 250 individuals with PTH measurements were included in the analysis. Obese individuals (n = 141) experienced a steep reduction of 3-month PTH from placebo to 1,000IU/day of vitamin D3 supplementation, but no further reduction at 2,000 or 4,000IU/day. For non-obese individuals (n = 109), the reduction of 3-month PTH was approximately linear for increasing vitamin D3 doses. At supplementation of 2,000 to 4,000IU/day, 3-month 25(OH)vitamin D levels were high in both non-obese and obese individuals, but the 3-month PTH levels remained about 10pg/mL higher in individuals with obesity. Our findings suggest that excess adiposity confers resistance to vitamin D efficacy in suppressing PTH levels, even when given at high doses.

Efficacy of two different doses of oral vitamin D supplementation on inflammatory biomarkers and maternal and neonatal outcomes.

Hypovitaminosis D during pregnancy is suggested to have a link with complications in both mother and infant. We aimed to evaluate the efficacy of two doses of vitamin D3 supplementation during pregnancy on maternal and cord blood vitamin D status, inflammatory biomarkers, and maternal and neonatal outcomes. A total of 84 pregnant women (gestational age of <12weeks) were randomly allocated to one of two groups: (a) 1,000-IU/d vitamin D and (b) 2,000IU/d. Biochemical assessments (25-hydroxycalciferol (25(OH)D), hs-CRP, and cell-culture supernatant concentrations of IL-1β, IL-6, and TNF-α) of mothers were performed at the beginning and 34weeks of gestation. Assessments of infants at delivery comprised cord blood serum concentrations of 25(OH)D, hs-CRP, IL-1β, IL-6, TNF-α, birth sizes, and Apgar score. Circulating concentrations of 25(OH)D increased in both intervention groups with more increment in 2,000IU/d than in 1,000IU/d (46.7±30.7 vs. 24.0±21.07nmolL-1 , P=.001). Concentrations of TNF-α decreased significantly in group 2,000 (-913.1±1261.3ngL-1 , P=.01). The cord blood concentration of IL-6 in group 2,000IU/d, compared with 1,000IU/d, was significantly lower (25.9±32.0 vs. 4.6±1.4ngL-1 , P=.03). The birth sizes including weight, length, and head circumference of the infants of group 2,000IU/d were significantly higher than the infants' of group 1,000IU/d. Supplementation with 2,000-IU/d vitamin D3 is more effective than 1,000IU/d in pregnant women in terms of increasing circulating 25(OH)D, ameliorating pro-inflammatory markers notably TNF-α in mother and IL-6 in cord blood, and improving neonatal outcomes including the birth sizes.

Impact of three different daily doses of vitamin D3 supplementation in healthy schoolchildren and adolescents from North India: a single-blind prospective randomised clinical trial.

In India, there is a lack of information about the adequate daily dose of vitamin D3 supplementation in school children. Hence, we undertook this study to evaluate the adequacy and efficacy of different doses of vitamin D3 in schoolchildren. A total of 1008 vitamin D-deficient (VDD) children, aged 6-16 years with serum 25-hydroxyvitamin D (25(OH)D) levels &lt;50nmol/l, were cluster randomised into three groups (A-344, B-341 and C-232) for supplementation (600, 1000 and 2000 IU daily) of vitamin D3 under supervision for 6 months. Of the 1008 subjects who completed the study, 938 (93 %) were compliant. Baseline and post-supplementation fasting blood and urine samples were evaluated for Ca, phosphates, alkaline phosphatase, 25(OH)D and parathormone and urine Ca:creatinine ratio. The mean age of the subjects was 11·7 (sd 2·4) years, and the overall mean baseline serum 25(OH)D level was 24·3 (SD 9·5)nmol/l. Post-supplementation rise in serum 25(OH)D in compliant group was maximum with 2000 IU (70·0 (SD 30·0)nmol/l), followed by 1000 IU (46·8 (SD 22·5)nmol/l) and 600 IU (36·5 (SD 18·5)nmol/l), and serum 25(OH)D levels of ≥50nmol/l were achieved in 71·5, 81·8 and 92·9 % by groups A, B and C, respectively. Secondary hyperparathyroidism decreased from 31·7 to 8·4 % post-supplementation. Two participants developed hypercalciuria, but none developed hypercalcaemia. Children with VDD benefit maximum with the daily supplementation of 2000 IU of vitamin D3. Whether recommendations of 400 IU/d by Indian Council of Medical Research or 600 IU by Indian Academy of Pediatrics or Institute of Medicine would suffice to achieve vitamin D sufficiency in children with VDD remains debatable.

Vitamin D3 Supplementation on Immune Functions and Upper Respiratory Track Infection in Male Taekwondo Athletes

Vitamin D plays an important role for immune functions. Insufficient serum 25(OH)D concentration during winter season may be associated with increased risk of upper respiratory tract infection (URTI) in athletes. PURPOSE: This study was aimed to determine the effects of vitamin D3 supplementation on immune functions and URTI in male taekwondo athletes. METHODS: Twenty-five male taekwondo (TKD) athletes, aged 19-22 years with vitamin D deficiency (25(OH)D; 12.3±2.78 ng/ml), participated in this study. They were randomly assigned to receive 5,000 IU/day of vitamin D3 capsule (N=13) or placebo (N=12) during 4 weeks of winter training. Blood samples were collected two times (pre- and post-tests) to analyze serum 25(OH)D concentration. Saliva samples were collected three times (1st, 2nd, and 4th week) to analyze the salivary immunoglobulin A (SIgA) and lactoferrin concentrations. URTI symptoms were reported daily during 4 weeks of training. Repeated measures ANOVAs were performed and significant level was set at p<.05. RESULTS: The serum 25(OH)D concentration increased by 255.6% in supplementation group, but this level did not change in placebo group (F=247.50, p<.001). SIgA (F=23.00, p<.001) significantly increased in both groups during the study period, but salivary lactoferrin level (F=5.79, p=.011) increased only in placebo group at the 2nd week of training. URTI symptoms significantly decreased only in supplementation group (F=5.456, p=.005) throughout the study. CONCLUSIONS: The present study found that high dose of vitamin D3 supplementation (5,000 IU/day) increased the serum 25(OH)D concentration to sufficient level (40.1±6.79 ng/ml), and decreased URTI symptoms during winter training. Our findings suggest that vitamin D3 supplementation during winter training may provide potential benefits for preventing URTI in male taekwondo athletes with vitamin D deficient.

Randomized trial of two doses of vitamin D3 in preterm infants

BackgroundRecommendations for vitamin D supplementation for preterm infants span a wide range of doses. Response to vitamin D supplementation and impact on outcomes in preterm infants is not well understood.ObjectiveEvaluate serum 25(OH)D3 concentration changes after 4 weeks in response to two different doses of vitamin D3 supplementation in a population of premature infants and quantify the impact on NICU outcomes.Design32 infants born at 24–32 weeks gestation were prospectively randomized to receive 400 or 800 IU/day vitamin D3 supplementation. Serum 25(OH)D3 levels were measured every 4 weeks. The Wilcoxon signed rank test was used to compare serum levels of 25(OH)D3 at 4 weeks and each subsequent time point. A p-value of <0.05 was considered statistically significant.ResultsSerum 25(OH)D3 levels at birth were 41.9 and 42.9 nmol/l for infants in the 400 IU group and 800 IU group, respectively (p = 0.86). Cord 25(OH)D3 concentrations significantly correlated with gestational age (r = 0.40, p = 0.04). After 4 weeks of D3 supplementation, median 25(OH)D3 levels increased in both groups (84.6vs. 105.3 nmol/l for 400 vs. 800 IU/day respectively, with significantly more improvement in the higher dose (p = 0.048). Infants in the 400 IU group were significantly more likely to have dual energy x-ray absorptiometry (DEXA) bone density measurements <10 percentile (56% vs 16%, p = 0.04).ConclusionsImprovement in 25(OH)D3 levels at 4 weeks, bone density, and trends towards improvement in linear growth support consideration of a daily dose of 800 IU of vitamin D for infants <32 weeks cared for in the NICU.

Effects of different doses of vitamin D3 supplementation in young premenopausal women on depression and hormonal status

Effects of different doses of vitamin D3 supplementation in young premenopausal women on depression and hormonal status

Acute Effects of Vitamin D3 Supplementation on Muscle Strength in Judoka Athletes

Indoor athletes have been shown to be prone to vitamin D3 deficiency. The aim of the study was to examine the acute effects of vitamin D supplementation on muscle function using isokinetic dynamometry. Randomized placebo-controlled, double-blind study. Institutional. Adult male white national level judoka athletes (n = 22) who were involved in full-time training. Exclusion criteria were vitamin supplementation, overseas travel to sunny climes, and/or an injury incurred during the last 3 months before testing. Subjects were randomly allocated to the treatment (150 000IU vitamin D3) or placebo and given blinded supplements by an independent researcher. Participants were tested twice, 8 days apart, on a Monday morning before the start of judo training and after 2 days of rest. A 5 to 7 mL of blood sample was collected followed by isokinetic concentric quadriceps and hamstring muscle function assessments on the right leg at 30 and 200°·s. Repeated-measures analysis of variance was used to analyze isokinetic muscle force and serum 25(OH)D3. Regression to the mean was used to examine changes in 25(OH)D3 levels over the study period. The treatment group demonstrated a significant increase in serum 25(OH)D levels (34%, P ≤ 0.001) and muscle strength (13%, P = 0.01) between days 1 and 8. No significant differences were found for the placebo group for the same period. A single bolus of 150 000IU vitamin D3 had a significant positive effect on serum 25(OH)D levels and muscle function in vitamin D insufficient elite indoor athletes. Serum 25(OH)D3 levels of indoor athletes should be monitored throughout the year and especially during winter months. Beneficial responses, in muscle strength and serum 25(OH)D3, to 1 dose of vitamin D3 supplementation can be observed within 1 week of ingestion. Muscle strength is linked to serum 25(OH)D levels.

Vitamin D supplementation during pregnancy

Vitamin D requirements have become one of the most highly debated and controversial topics in nutrition. Recommendations for vitamin D intake during pregnancy are a central part of this discussion. The publication of a controlled trial of vitamin D supplementation in pregnant women by Hollis and coworkers in this issue of JBMR provides important data about the effects of different doses of vitamin D3 supplementation on serum 25-hydroxyvitamin D [25(OH)D] levels. (1) Hollis and coworkers report that providing daily supplements of 2000 or 4000 IU of vitamin D3 during the second and third trimesters of pregnancy led to higher serum 25(OH)D concentrations in women during pregnancy and in their newborn infants than supplements of 400 IU/d. (1) As suggested by a footnote, further results from this controlled trial may be provided in the future in the peer-reviewed literature. For now, an evaluation of these results and how they might guide vitamin D recommendations during pregnancy is appropriate. In this report, (1) increases in both vitamin D supplementation and serum 25(OH)D level were associated with higher serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels. This outcome was the primary one for which this study was designed and sample size determined. However, there was no evidence of any clinical outcome differences based on supplement dose, and such outcomes were not part of the original study design. Specifically, there were no significant differences based on supplement dose in the 350 subjects who completed the study in C-section rate, gestational age, birth weight, or neonatal intensive-care unit (NICU) admission rate. Rates of preeclampsia and preterm birth based on supplement dose were not provided. Although NICU admission is not a complete assessment measure for neonatal outcome, these findings provide evidence that different levels of vitamin D supplementation had no significant positive or negative effect on the need for advanced neonatal care. Of note is that although an intention-to-treat analysis was indicated in the methods, outcome data are not available for the over 100 subjects who discontinued the study or were withdrawn from it without a known pregnancy loss. Outcomes such as neonatal or maternal bone mineral content, postneonatal infant health outcomes, and long-term bone outcomes for mother and infant are not provided in this report. (1) There is conflicting scientific evidence regarding the long-term effects of maternal vitamin D supplementation on childhood health outcomes (2,3) and no evidence about long- or short-term outcomes for maternal bone health from supplementation at doses of 4000 IU/d during pregnancy.

Efficacy of vitamin D3 supplementation in preventing fractures in elderly women: A meta-analysis

Background:The efficacy of vitamin D3 in preventing fractures and falls has been explored in a number of clinical trials. However, recent evidence revealed new questions about the adequate doses of vitamin D3 supplementation and its efficacy in fracture prevention independent of calcium supplements for various types of fractures.Objective:To conduct a meta-analysis to estimate the effectiveness of 800 IU daily vitamin D3 supplementation for increasing bone mineral density (BMD) and preventing fractures in postmenopausal women.Methods:Medline and EMBASE were searched for controlled trials comparing the effectiveness of cholecalciferol (vitamin D3) against placebo with or without background calcium supplementation in the treatment of postmenopausal women.Results:Eight controlled trials evaluating the effect of vitamin D3 supplementation with or without calcium were assessed. Of 12 658 women included in a Bayesian meta-analysis, 6089 received vitamin D3 (with or without calcium) and 6569 received placebo (with or without calcium). Compared to placebo, vitamin D3 with calcium supplementation showed beneficial effects on the incidence of non-vertebral (odds ratio [OR] 0.77, 95% credibility limit [CL] 0.6–0.93) and hip (OR 0.70, 95% CL 0.53–0.90) fractures, while the effects on non-vertebral-non-hip fractures (OR 0.84, 95% CL 0.67–1.04) % point increase) were associated with more uncertainty. Vitamin D3 supplementation showed a 70% probability of being a better treatment than placebo for the prevention of non-vertebral fractures, hip fractures, and non-vertebral, non-hip fractures. Compared to calcium supplementation, vitamin D3 plus calcium reduced non-vertebral fractures (OR 0.68, 95% CL 0.43–1.01) and non-vertebral, non-hip fractures (OR 0.64, 95% CL 0.38–0.99), but did not reduce hip fractures (OR 1.03, 95% CL 0.39–2.25). Key limitations to this analysis include a small number of studies and heterogeneity in the study populations.Conclusions:This meta-analysis supports the use of vitamin D3 of 800 IU daily to reduce the incidence of osteoporotic non-vertebral, hip, and non-vertebral-non-hip fractures in elderly women. Vitamin D3 with calcium appears to achieve benefits above those attained with calcium supplementation alone for non-vertebral and non-vertebral-non-hip fractures.

How Much Vitamin D3 Do the Elderly Need?

Background: Vitamin D insufficiency poses a problem in many parts of the world, the elderly being an especially vulnerable group. This insufficiency results from an inadequate amount of sunshine and a low dietary intake of vitamin D. Typically, insufficiency is accompanied with high intact parathyroid hormone, (S-iPTH) concentrations.Aims of the Study: We studied how serum 25-hydroxy vitamin D (S-25-OHD) concentrations respond to different doses of vitamin D3 supplementation. Secondly to determine the smallest efficient dose to maintain serum 25-OHD concentration above the insufficiency level. We also studied which dose would be efficient in decreasing S-iPTH concentration in these subjects.Subjects and Methods: Forty-nine 65- to 85-year-old women participated. The women were randomly assigned into one of four groups receiving 0 (placebo), 5, 10 or 20 μg of vitamin D3 daily for 12 weeks. Fasting morning blood was drawn at the beginning of the study, and thereafter every second week. Calciotropic variables were assessed from serum and urine samples.Results: The S-25-OHD concentration increased significantly (p < 0.001) in all supplemented groups [5 μg: by 10.9 (8.5) nmol/L, 10 μg: by 14.4 (6.9) nmol/L, 20 μg: by 23.7 (11.9) nmol/L], whereas it decreased in the placebo group by 8.3 (13.2) nmol/L. Equilibrium in S-25-OHD concentration was reached in all groups after 6 weeks of supplementation at 57.7 (8.9) nmol/L, 59.9 (8.9) nmol/L and 70.9 (8.9) nmol/L in the groups with increasing vitamin D supplementation. The dose-response to supplementation decreased with increasing vitamin D status at baseline, r = −0.513, p = 0.002. S-iPTH tended to decrease in those with highest dose response to supplementation.Conclusions: A clear dose response was noted in S-25-OHD to different doses of vitamin D3. The recommended dietary intake of 15 μg is adequate to maintain the S-25-OHD concentration around 40–55 nmol/L during winter, but if the optimal S-25-OHD is higher than that even higher vitamin D intakes are needed. Interestingly, subjects with lower vitamin D status at baseline responded more efficiently to supplementation than those with more adequate status.