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Nutrients May 2020Vitamin D deficiency is a global health problem due to its high prevalence and its negative consequences on musculoskeletal and extra-skeletal health. In our comparative... (Review)
Review
Vitamin D deficiency is a global health problem due to its high prevalence and its negative consequences on musculoskeletal and extra-skeletal health. In our comparative review of the two exogenous vitamin D supplementation options most used in our care setting, we found that cholecalciferol has more scientific evidence with positive results than calcifediol in musculoskeletal diseases and that it is the form of vitamin D of choice in the most accepted and internationally recognized clinical guidelines on the management of osteoporosis. Cholecalciferol, unlike calcifediol, guarantees an exact dosage in IU (International Units) of vitamin D and has pharmacokinetic properties that allow either daily or even weekly, fortnightly, or monthly administration in its equivalent doses, which can facilitate adherence to treatment. Regardless of the pattern of administration, cholecalciferol may be more likely to achieve serum levels of 25(OH)D (25-hydroxy-vitamin D) of 30-50 ng/mL, an interval considered optimal for maximum benefit at the lowest risk. In summary, the form of vitamin D of choice for exogenous supplementation should be cholecalciferol, with calcifediol reserved for patients with liver failure or severe intestinal malabsorption syndromes.
Topics: Animals; Calcifediol; Cholecalciferol; Dietary Supplements; Humans; Musculoskeletal System; Osteoporosis; Vitamin D; Vitamin D Deficiency
PubMed: 32486496
DOI: 10.3390/nu12061617 -
International Journal of Molecular... Feb 2023Vitamin D is a fat-soluble secosteroid that exists in two forms: vitamin D and vitamin D [...].
Vitamin D is a fat-soluble secosteroid that exists in two forms: vitamin D and vitamin D [...].
Topics: Cholecalciferol; Ergocalciferols; Vitamin D; Vitamin D-Binding Protein
PubMed: 36902073
DOI: 10.3390/ijms24054642 -
JAMA Aug 2020Low levels of 25-hydroxyvitamin D have been associated with higher risk for depression later in life, but there have been few long-term, high-dose large-scale trials. (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial.
IMPORTANCE
Low levels of 25-hydroxyvitamin D have been associated with higher risk for depression later in life, but there have been few long-term, high-dose large-scale trials.
OBJECTIVE
To test the effects of vitamin D3 supplementation on late-life depression risk and mood scores.
DESIGN, SETTING, AND PARTICIPANTS
There were 18 353 men and women aged 50 years or older in the VITAL-DEP (Vitamin D and Omega-3 Trial-Depression Endpoint Prevention) ancillary study to VITAL, a randomized clinical trial of cardiovascular disease and cancer prevention among 25 871 adults in the US. There were 16 657 at risk for incident depression (ie, no depression history) and 1696 at risk for recurrent depression (ie, depression history but no treatment for depression within the past 2 years). Randomization occurred from November 2011 through March 2014; randomized treatment ended on December 31, 2017, and this was the final date of follow-up.
INTERVENTION
Randomized assignment in a 2 × 2 factorial design to vitamin D3 (2000 IU/d of cholecalciferol) and fish oil or placebo; 9181 were randomized to vitamin D3 and 9172 were randomized to matching placebo.
MAIN OUTCOMES AND MEASURES
The primary outcomes were the risk of depression or clinically relevant depressive symptoms (total of incident and recurrent cases) and the mean difference in mood scores (8-item Patient Health Questionnaire depression scale [PHQ-8]; score range, 0 points [least symptoms] to 24 points [most symptoms]; the minimal clinically important difference for change in scores was 0.5 points).
RESULTS
Among the 18 353 randomized participants (mean age, 67.5 [SD, 7.1] years; 49.2% women), the median treatment duration was 5.3 years and 90.5% completed the trial (93.5% among those alive at the end of the trial). Risk of depression or clinically relevant depressive symptoms was not significantly different between the vitamin D3 group (609 depression or clinically relevant depressive symptom events; 12.9/1000 person-years) and the placebo group (625 depression or clinically relevant depressive symptom events; 13.3/1000 person-years) (hazard ratio, 0.97 [95% CI, 0.87 to 1.09]; P = .62); there were no significant differences between groups in depression incidence or recurrence. No significant differences were observed between treatment groups for change in mood scores over time; mean change in PHQ-8 score was not significantly different from zero (mean difference for change in mood scores, 0.01 points [95% CI, -0.04 to 0.05 points]).
CONCLUSIONS AND RELEVANCE
Among adults aged 50 years or older without clinically relevant depressive symptoms at baseline, treatment with vitamin D3 compared with placebo did not result in a statistically significant difference in the incidence and recurrence of depression or clinically relevant depressive symptoms or for change in mood scores over a median follow-up of 5.3 years. These findings do not support the use of vitamin D3 in adults to prevent depression.
TRIAL REGISTRATION
ClinicalTrials.gov Identifiers: NCT01169259 and NCT01696435.
Topics: Affect; Aged; Cholecalciferol; Depression; Depressive Disorder; Dietary Supplements; Double-Blind Method; Female; Humans; Incidence; Male; Middle Aged; Recurrence; Surveys and Questionnaires; Vitamins
PubMed: 32749491
DOI: 10.1001/jama.2020.10224 -
Nutrients Mar 2022Vitamin D deficiency is the main cause of nutritional rickets in children and osteomalacia in adults. There is consensus that nutritional access to vitamin D can be... (Review)
Review
Vitamin D deficiency is the main cause of nutritional rickets in children and osteomalacia in adults. There is consensus that nutritional access to vitamin D can be estimated by measuring serum concentrations of 25OHD and vitamin D deficiency can thus be considered as calcifediol deficiency. However, the threshold for vitamin D/calcifediol sufficiency remains a matter of debate. Vitamin D/calcifediol deficiency has been associated with musculoskeletal effects but also multiple adverse extra-skeletal consequences. If these consequences improve or if they can be treated with vitamin D supplementation is still unclear. Observational studies suggest a higher infection risk in people with low calcifediol levels. There is also a consistent association between serum calcifediol and cardiovascular events and deaths, but large-scale, long-term intervention studies did not show any benefit on cardiovascular outcomes from supplementation, at least not in subjects without clear vitamin D deficiency. Cancer risk also did not change with vitamin D treatment, although there are some data that higher serum calcifediol is associated with longer survival in cancer patients. In pregnant women, vitamin D supplementation decreases the risk of pre-eclampsia, gestational diabetes mellitus, and low birth weight. Although preclinical studies showed that the vitamin D endocrine system plays a role in certain neural cells as well as brain structure and function, there is no evidence to support a beneficial effect of vitamin D in neurodegenerative diseases. Vitamin D supplementation may marginally affect overall mortality risk especially in elderly subjects with low serum calcifediol concentrations.
Topics: Aged; Calcifediol; Child; Cholecalciferol; Female; Humans; Pregnancy; Risk Factors; Vitamin D; Vitamin D Deficiency
PubMed: 35334824
DOI: 10.3390/nu14061168 -
JCI Insight Oct 2017Our goal was to identify changes in the metabolome in multiple sclerosis (MS) and how vitamin D supplementation alters metabolic profiles in MS patients and healthy... (Clinical Trial)
Clinical Trial
BACKGROUND
Our goal was to identify changes in the metabolome in multiple sclerosis (MS) and how vitamin D supplementation alters metabolic profiles in MS patients and healthy controls.
METHODS
We applied global untargeted metabolomics to plasma from a cross-sectional cohort of age- and sex-matched MS patients and controls and a second longitudinal cohort of MS patients and healthy controls who received 5,000 IU cholecalciferol daily for 90 days. We applied partial least squares discriminant analysis, weighted correlation network analysis (WGCNA), and pathway analysis to the metabolomics data. Generalized estimating equations models were used to assess change in WGCNA-identified module scores or metabolite pathways with vitamin D supplementation.
RESULTS
Utilizing multiple analytical techniques, we identified metabolic alterations in oxidative stress (γ-glutamyl amino acid, glutathione) and xenobiotic metabolism (benzoate, caffeine) in MS patients compared with healthy controls in the first cohort. In the vitamin D supplementation cohort, we identified two sets of metabolites altered differentially between MS patients and healthy controls with vitamin D supplementation. The first included markers of oxidative stress and protein oxidation (P = 0.006), while the second contained lysolipids and fatty acids (P = 0.03).
CONCLUSIONS
Using metabolomics, we identified alterations in oxidative stress and xenobiotic metabolism in MS patients and subsequently demonstrated a reduction of oxidative stress markers with vitamin D supplementation in healthy controls but not in MS patients. We demonstrate the utility of metabolomics in identifying aberrant metabolic processes and in monitoring the ability of therapeutic interventions to correct these abnormalities.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01667796.
FUNDING
This study was supported by NIH grant K23 NS067055, grants from the Race to Erase MS, the National Multiple Sclerosis Society, the American Academy of Neurology, and North American Research Committee on Multiple Sclerosis.
Topics: Adult; Case-Control Studies; Cholecalciferol; Cross-Sectional Studies; Dietary Supplements; Female; Humans; Metabolome; Metabolomics; Middle Aged; Multiple Sclerosis; Oxidative Stress; Xenobiotics
PubMed: 28978801
DOI: 10.1172/jci.insight.95302 -
Diabetes Research and Clinical Practice Apr 2021To assess the efficacy of vitamin D3 or B12 supplementation during pregnancy. (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
To assess the efficacy of vitamin D3 or B12 supplementation during pregnancy.
METHODS
Pregnant women at 6-14 weeks in the intervention arm received oral high dose intermittent vitamin D3 and/or low dose B12 supplementation if they had vitamin D or vitamin B12 deficiency. The control arm received prescribed dietary instruction only. An additional observational arm for those mothers at booking with normal vitamin D and vitamin B12 level was also recruited. All groups received standard care during pregnancy.
RESULTS
The primary endpoint of either vitamin D or B12 at term was not met. At baseline 25% participants in both the interventional and control arms had severe D deficiency (<30 nmol/l), reducing to under 3.4% in both groups. No maternal differences in vitamin D or B12 levels were found at delivery between the intervention, control, or observational groups. No significant difference in any of the pregnancy or birth outcomes was observed between three groups.
CONCLUSIONS
In this study, oral supplementation of high dose intermittent vitamin D or low dose vitamin B12 regime failed to correct the relevant nutritional deficiencies in Bangladeshi pregnant women as per protocol. Both dietary supplementation and high dose vitamin D corrected severe vitamin deficiency.
Topics: Adolescent; Adult; Cholecalciferol; Dietary Supplements; Female; Humans; Pilot Projects; Pregnancy; Pregnancy Complications; Vitamin B 12; Young Adult
PubMed: 33662489
DOI: 10.1016/j.diabres.2021.108728 -
European Journal of Nutrition Jun 2023In addition to the role of vitamin D in bone mineralization, calcium and phosphate homeostasis, and skeletal health, evidence suggests an association between vitamin D... (Review)
Review
BACKGROUND
In addition to the role of vitamin D in bone mineralization, calcium and phosphate homeostasis, and skeletal health, evidence suggests an association between vitamin D deficiency and a wide range of chronic conditions. This is of clinical concern given the substantial global prevalence of vitamin D deficiency. Vitamin D deficiency has traditionally been treated with vitamin D (cholecalciferol) or vitamin D (ergocalciferol). Calcifediol (25-hydroxyvitamin D) has recently become available more widely.
METHODS
By means of targeted literature searches of PubMed, this narrative review overviews the physiological functions and metabolic pathways of vitamin D, examines the differences between calcifediol and vitamin D, and highlights clinical trials conducted with calcifediol in patients with bone disease or other conditions.
RESULTS
For supplemental use in the healthy population, calcifediol can be used at doses of up to 10 µg per day for children ≥ 11 years and adults and up to 5 µg/day in children 3-10 years. For therapeutic use of calcifediol under medical supervision, the dose, frequency and duration of treatment is determined according to serum 25(OH)D concentrations, condition, type of patient and comorbidities. Calcifediol differs pharmacokinetically from vitamin D in several ways. It is independent of hepatic 25-hydroxylation and thus is one step closer in the metabolic pathway to active vitamin D. At comparable doses to vitamin D, calcifediol achieves target serum 25(OH)D concentrations more rapidly and in contrast to vitamin D, it has a predictable and linear dose-response curve irrespective of baseline serum 25(OH)D concentrations. The intestinal absorption of calcifediol is relatively preserved in patients with fat malabsorption and it is more hydrophilic than vitamin D and thus is less prone to sequestration in adipose tissue.
CONCLUSION
Calcifediol is suitable for use in all patients with vitamin D deficiency and may be preferable to vitamin D for patients with obesity, liver disease, malabsorption and those who require a rapid increase in 25(OH)D concentrations.
Topics: Adult; Child; Humans; Calcifediol; Dietary Supplements; Vitamin D; Vitamins; Cholecalciferol; Vitamin D Deficiency
PubMed: 36862209
DOI: 10.1007/s00394-023-03103-1 -
The American Journal of Clinical... Aug 2022Vitamin D deficiency is frequently found in patients with chronic obstructive pulmonary disease (COPD). Vitamin D has antimicrobial, anti-inflammatory, and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Vitamin D deficiency is frequently found in patients with chronic obstructive pulmonary disease (COPD). Vitamin D has antimicrobial, anti-inflammatory, and immunomodulatory effects. Therefore, supplementation may prevent COPD exacerbations, particularly in deficient patients.
OBJECTIVES
We aimed to assess the effect of vitamin D supplementation on exacerbation rate in vitamin D-deficient patients with COPD.
METHODS
We performed a multicenter, double-blind, randomized controlled trial. COPD patients with ≥1 exacerbations in the preceding year and a vitamin D deficiency (15-50 nmol/L) were randomly allocated in a 1:1 ratio to receive either 16,800 International Units (IU) vitamin D3 or placebo once a week during 1 y. Primary outcome of the study was exacerbation rate. Secondary outcomes included time to first and second exacerbations, time to first and second hospitalizations, use of antibiotics and corticosteroids, pulmonary function, maximal respiratory mouth pressure, physical performance, skeletal muscle strength, systemic inflammatory markers, nasal microbiota composition, and quality of life.
RESULTS
The intention-to-treat population consisted of 155 participants. Mean ± SD serum 25-hydroxyvitamin D [25(OH)D] concentration after 1 y was 112 ± 34 nmol/L in the vitamin D group, compared with 42 ± 17 nmol/L in the placebo group. Vitamin D supplementation did not affect exacerbation rate [incidence rate ratio (IRR): 0.90; 95% CI: 0.67, 1.21]. In a prespecified subgroup analysis in participants with 25(OH)D concentrations of 15-25 nmol/L (n = 31), no effect of vitamin D supplementation was found (IRR: 0.91; 95% CI: 0.43, 1.93). No relevant differences were found between the intervention and placebo groups in terms of secondary outcomes.
CONCLUSIONS
Vitamin D supplementation did not reduce exacerbation rate in COPD patients with a vitamin D deficiency.This trial was registered at clinicaltrials.gov as NCT02122627.
Topics: Cholecalciferol; Dietary Supplements; Double-Blind Method; Humans; Pulmonary Disease, Chronic Obstructive; Quality of Life; Vitamin D; Vitamin D Deficiency
PubMed: 35383823
DOI: 10.1093/ajcn/nqac083 -
Ageing Research Reviews Jun 2023To evaluate the effect of vitamin D supplementation on cancer mortality in the general population and on prognosis in cancer patients, a systematic review and... (Meta-Analysis)
Meta-Analysis
To evaluate the effect of vitamin D supplementation on cancer mortality in the general population and on prognosis in cancer patients, a systematic review and meta-analysis of randomised, placebo-controlled trials (RCTs) and individual patient data (IPD) was conducted. Overall, 14 RCTs with a total of 104,727 participants (2015 cancer deaths) were identified and 7 RCTs, including 90 % of all study participants (n = 94,068), could be included in the IPD meta-analyses. The main meta-analysis of the 14 RCTs yielded a statistically non-significant reduction in cancer mortality by 6 % (risk ratio (RR) [95%-confidence interval (95%CI)]: 0.94 [0.86-1.02]). Subgroup analyses revealed a 12 % lower cancer mortality in the vitamin D group compared with the placebo group in 10 trials with a daily dosing regimen (RR [95%CI]: 0.88 [0.78-0.98]), whereas no mortality reduction was seen in 4 trials using a bolus regimen (RR [95%CI]: 1.07 [0.91-1.24]; p-value for interaction: 0.042). The IPD meta-analysis (RR [95%CI]: 0.93 [0.84; 1.02]) confirmed the finding of all trials. The IPD were used to test effect modification by age, sex, body mass index, ethnicity, baseline serum 25-hydroxyvitamin D concentration, adherence and cancer-related factors but no statistically significant findings were obtained in meta-analyses of all trials. When restricted to trials with daily dosing in a post-hoc analysis, adults aged ≥ 70 years (RR [95%CI]: 0.83 [0.77; 0.98]) and subjects with vitamin D therapy initiation before cancer diagnosis (RR [95%CI]: 0.87 [0.69; 0.99]) appeared to benefit most from daily vitamin D supplementation. Measurements of baseline 25-hydroxyvitamin D levels and inclusion of other than non-Hispanic White adults were too sparse in the trials to draw conclusions. Results for all-cause and cancer-specific survival of participants with cancer were comparable to those obtained in the general population for cancer mortality. In conclusion, vitamin D did not reduce cancer mortality in the main meta-analysis of all RCTs because the observed risk reduction by 6 % was not statistically significant. However, a subgroup analysis revealed that vitamin D administered daily, in contrast to bolus supplementation, reduced cancer mortality by 12 %.
Topics: Humans; Cholecalciferol; Dietary Supplements; Neoplasms; Prognosis; Vitamin D
PubMed: 37004841
DOI: 10.1016/j.arr.2023.101923 -
The Journal of Clinical Endocrinology... Apr 2017Vitamin D deficiency disproportionately affects nonwhite individuals. Controversy persists over how to best restore low 25D levels, and how to best define vitamin D... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Vitamin D deficiency disproportionately affects nonwhite individuals. Controversy persists over how to best restore low 25D levels, and how to best define vitamin D status [total (protein bound plus free) vs free 25D].
OBJECTIVE
To assess the effects of vitamin D3 (cholecalciferol, or D3) vs 25-hydroxyvitamin D3 (calcifediol, or 25D3) on total and free 25D in a multiethnic cohort of adults, and whether change in parathyroid hormone (PTH) is more strongly associated with total vs free 25D.
DESIGN
Sixteen-week randomized controlled trial. Biochemistries at 0, 4, 8, and 16 weeks.
SETTING
Academic medical center.
PARTICIPANTS
Thirty-five adults ≥18 years of age with 25D levels <20 ng/mL.
INTERVENTION
Sixty micrograms (2400 IU)/d of D3 or 20 μg/d of 25D3.
MAIN OUTCOME MEASURES
Total and free 25D, and PTH.
RESULTS
Baseline total (16.2 ± 3.7 vs 17.0 ± 2.5 ng/mL; P = 0.4) and free (4.2 ± 0.8 vs 4.7 ± 1.0 pg/mL; P = 0.2) 25D were similar between D3 and 25D3 groups, respectively; 25D3 increased total (+25.5 vs +13.8 ng/mL; P = 0.001) and free (+6.6 vs +3.5 pg/mL; P = 0.03) 25D more than D3. By 4 weeks, 87.5% of 25D3 participants had total 25D levels ≥30 ng/mL, compared with 23.1% of D3 participants (P = 0.001). Change in PTH was associated with both total (P = 0.01) and free 25D (P = 0.04).
CONCLUSIONS
25D3 increased total and free 25D levels more rapidly than D3, regardless of race/ethnicity. Free and total 25D were similarly associated with change in PTH.
Topics: Adult; Calcifediol; Calcium; Cholecalciferol; Female; Humans; Male; Middle Aged; Parathyroid Hormone; Vitamin D; Vitamin D Deficiency; Young Adult
PubMed: 28187226
DOI: 10.1210/jc.2016-3919