Associations of 25-Hydroxyvitamin D Status and Supplementation with Adverse Outcomes in Geriatric Rehabilitation Inpatients: RESORT.

OBJECTIVES: Geriatric rehabilitation inpatients are at a higher risk of 25-hydroxyvitamin D (25(OH)D) deficiency due to poor nutrition and low sunlight exposure. This study aimed to evaluate the prevalence of 25-hydroxyvitamin (25(OH)D) deficiency and supplementation and to investigate their association with adverse health outcomes in geriatric rehabilitation inpatients. DESIGN: Prospective, observational and longitudinal study. SETTING AND PARTICIPANTS: Geriatric rehabilitation inpatients admitted to geriatric rehabilitation wards at the Royal Melbourne Hospital (Melbourne, Australia) from 16th, October 2017 and discharged until 18th, March 2020 in the REStORing health of acutely unwell adulTs (RESORT) study were included. METHODS: 25(OH)D levels measured close to rehabilitation admission were classified as sufficiency (>54 nmol/L), insufficiency (26-54 nmol/L), or deficiency (<26 nmol/L). The usage of vitamin D supplementation was extracted from medication records. Outcomes included incidence of institutionalization at three-month post-discharge, in-hospital mortality and post-discharge mortality. RESULTS: The median age of 1328 geriatric rehabilitation inpatients was 83.9 years (IQR: 78.1-88.7, 58.6% female). 25(OH)D deficiency and insufficiency were present in 8.1% and 26.4% of inpatients, respectively; 74.2% used vitamin D supplementation. 25(OH)D deficiency was associated with higher odds of institutionalization (odds ratio (OR): 1.88, 95% confidence interval (CI): 1.14-3.11), in-hospital mortality (OR: 3.30, 95% CI: 1.54-7.07) and higher risks of one-year mortality (hazard ratio (HR): 1.77, 95% CI: 1.17-2.69) compared to 25(OH)D sufficiency but not with three-month mortality. 25(OH)D insufficiency was not associated with outcomes. Patients who did not use supplementation and had 25(OH)D insufficiency or deficiency had significantly higher in-hospital mortality compared to those who used supplementation. CONCLUSIONS: Among geriatric rehabilitation inpatients, 25(OH)D deficiency was associated with institutionalization, in-hospital mortality and one-year mortality. Attention to monitor the vitamin D status is of upmost importance during hospitalization.

Meta-Analysis of European Clinical Trials Characterizing the Healthy-Adult Serum 25-hydroxyvitamin D Response to Vitamin D Supplementation.

To obtain reliable data that allow health authorities to re-evaluate recommendations for oral vitamin D uptake, we conducted a meta-analysis to investigate the impact of supplementation on serum 25-hydroxyvitamin D (25(OH)D) levels in healthy adults in Europe. Of the publications identified (n = 4005) in our literature search (PUBMED, through 2 January 2022), 49 primary studies (7320 subjects, 73 study arms) were eligible for inclusion in our meta-analysis. The risk of bias was assessed using the Cochrane RoB tool based on seven categories, according to which each study is rated using three grades, and overall was rated as rather low. The median duration of intervention was 136.78 days (range, 1088 days); the mean weighted baseline 25(OH)D concentration and mean age were 33.01 vs. 33.84 nmol/L and 46.8 vs. 44.8 years in the vitamin D and placebo groups, respectively. Using random-effects models, 25(OH)D levels were increased by 36.28 nmol/L (95% CI 31.97-40.59) in the vitamin D group compared to the placebo, with a relative serum increment of 1.77 nmol/L per 2.5 µg of vitamin D daily. Notably, the relative serum 25(OH)D increment was affected by various factors, including the dosage and baseline serum 25(OH)D concentration, decreasing with increasing vitamin D doses and with increasing baseline serum levels. We estimate that supplementation in all healthy adults in Europe with appr. 25 µg of vitamin D (1000 IU) daily would raise serum 25(OH)D levels in 95% of the population to ≥50 nmol/L. Our work provides health authorities with reliable data that can help to re-evaluate recommendations for oral vitamin D supplementation.

Psoriasis and Vitamin D: A Systematic Review and Meta-Analysis.

Psoriasis is a chronic immune-dysregulated inflammatory disease and hypovitaminosis D is considered a risk factor. We conducted an online database search to review and meta-analyze the relationship between vitamin D, other bone metabolism parameters, and psoriasis. The efficacy of oral vitamin D supplementation in improving Psoriasis Area and Severity Index (PASI) was also evaluated. Non-original articles, case reports, and animal studies were excluded. Bias risk was assessed according to the Cochrane Collaboration's tool and the Newcastle-Ottawa scale in randomized controlled trials (RCTs) and case-control studies, respectively. Unstandardized mean differences were used for data synthesis. Twenty-three studies reported serum 25 hydroxyvitamin D (25(OH)D) levels in 1876 psoriasis patients and 7532 controls. Psoriasis patients had significantly lower 25(OH)D levels than controls (21.0 ± 8.3 vs. 27.3 ± 9.8, p < 0.00001). Conversely, 450 psoriasis patients had lower levels of parathormone than 417 controls (38.7 ± 12.8 vs. 43.7 ± 16.5, p = 0.015). Four RCTs examined the effect of oral vitamin D supplementation on psoriasis for 173 patients and 160 patients were treated with placebo. No significant differences were found in PASI after 3, 6, and 12 months of supplementation. It is shown that 25(OH)D serum levels are significantly lower in psoriasis, but, although the granularity of RCT methodology may have influenced the pooled analysis, vitamin D supplementation did not seem to improve clinical manifestations.

[Lifestyle medication vitamin D. What evidence is available?] / Lifestyle-Medikament Vitamin D. Was gibt es an Evidenz?

An undersupply of 25-(OH) vitamin D3 (calcifediol) exists in many countries with moderate sunlight, long winters and only moderate fish consumption. Risk groups for vitamin D3 deficiency are older persons over 65 years, geriatric persons in nursing homes, infants and children/adolescents. Therefore, there are also many situations in Germany which justify vitamin D substitution; however, vitamin D3 is currently praised as a "magic bullet" against everything. But what do the data look like? Where can it help and where can it not help?

Calcifediol (25OHD) Deficiency and Its Treatment in Women's Health and Fertility.

Currently, there is abundant scientific evidence showing that the vitamin D endocrine system (VDES) is a highly complex endocrine system with multiple actions in different regions of the body. The unequivocal presence of vitamin D receptors in different tissues related to fertility, and to specific aspects of women's health such as pregnancy, undoubtedly implies functions of this steroid hormone in both male and female fertility and establishes relationships with different outcomes of human gestation. In order to review the role of the VDES in human fertility, we evaluated the relationships established between 25-hydroxyvitamin D (calcifediol) deficiency and in vitro fertilization, as well as aspects related to ovarian reserve and fertility, and commonly diagnosed endocrinopathies such as polycystic ovary disease. Likewise, we briefly reviewed the relationships between calcifediol deficiency and uterine fibroids, as well as the role that treatment may have in improving human fertility. Finally, the best scientific evidence available on the consequences of calcifediol deficiency during pregnancy is reviewed in relation to those aspects that have accumulated the most scientific literature to date, such as the relationship with the weight of the newborn at the time of delivery, the appearance of preeclampsia, and the risk of developing gestational diabetes and its final consequences for the pregnancy. To date, there is no definitive consensus on the necessary dose for treatment of calcifediol deficiency in the therapeutic management of infertility or during pregnancy. Large prospective clinical intervention studies are needed to clarify the benefits associated with this supplementation and the optimal dose to use in each situation. Although most intervention studies to date have been conducted with cholecalciferol, due to its much longer history of use in daily care, the use of calcifediol to alleviate 25-hydroxyvitamin D deficiency seems safe, even during pregnancy. The unequivocal presence of vitamin D receptors in very different tissues related to human fertility, both male and female, as well as in structures typical of pregnancy, allows us to investigate the crucial role that this steroid hormone has in specific aspects of women's health, such as pregnancy and the ability to conceive. Well-designed clinical studies are needed to elucidate the necessary dose and the best form of treatment to resolve the very common calcifediol deficiency in women of reproductive age.

Vitamin D and its Possible Relationship to Neuroprotection in COVID-19: Evidence in the Literature.

Vitamin D is a hormone involved in the regulation of important biological processes such as signal transduction, immune response, metabolic regulation and also in the nervous and vascular systems. To date, coronavirus disease 2019 (COVID-19) infection does not have a specific treatment. However, various drugs have been proposed, including those that attenuate the intense inflammatory response, and recently, the use of vitamin D, in clinical trials, as part of the treatment of COVID-19 has provided promising results. It has been observed in some clinical studies that the use of cholecalciferol (vitamin D3) and its two metabolites the circulating form, calcidiol or calcifediol (25-hydroxycalciferol, 25-(OH)-D), and the active form, calcitriol (1,25-(OH)2-D), in different doses, improve the clinical manifestations, prognosis, and survival of patients infected with COVID-19 probably because of its anti-inflammatory, antiviral and lung-protective action. In relation to the central nervous system (CNS) it has been shown, in clinical studies, that vitamin D is beneficial in some neurological and psychiatric conditions because of its anti-inflammatory and antioxidant properties, modulation of neurotransmitters actions, and regulation of calcium homeostasis between other mechanisms. It has been shown that COVID-19 infection induces CNS complications such as headache, anosmia, ageusia, neuropathy, encephalitis, stroke, thrombosis, cerebral hemorrhages, cytotoxic lesions, and psychiatric conditions and it has been proposed that the use of dietary supplements, as vitamin and minerals, can be adjuvants in this disease. In this review, the evidence of the possible role of vitamin D, and its metabolites, as a protector against the neurological manifestations of COVID-19 was summarized.

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.

Calcifediol (25OH Vitamin D3) Deficiency: A Risk Factor from Early to Old Age.

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.

"Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study".

OBJECTIVE: The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19. DESIGN: Parallel pilot randomized open label, double-masked clinical trial. SETTING: University hospital setting (Reina Sofia University Hospital, Córdoba Spain.) PARTICIPANTS: 76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1). PROCEDURES: All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths. RESULTS: Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002-0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged. CONCLUSION: Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.

Vitamin D ameliorates adipose browning in chronic kidney disease cachexia.

Patients with chronic kidney disease (CKD) are often 25(OH)D3 and 1,25(OH)2D3 insufficient. We studied whether vitamin D repletion could correct aberrant adipose tissue and muscle metabolism in a mouse model of CKD-associated cachexia. Intraperitoneal administration of 25(OH)D3 and 1,25(OH)2D3 (75 µg/kg/day and 60 ng/kg/day respectively for 6 weeks) normalized serum concentrations of 25(OH)D3 and 1,25(OH)2D3 in CKD mice. Vitamin D repletion stimulated appetite, normalized weight gain, and improved fat and lean mass content in CKD mice. Vitamin D supplementation attenuated expression of key molecules involved in adipose tissue browning and ameliorated expression of thermogenic genes in adipose tissue and skeletal muscle in CKD mice. Furthermore, repletion of vitamin D improved skeletal muscle fiber size and in vivo muscle function, normalized muscle collagen content and attenuated muscle fat infiltration as well as pathogenetic molecular pathways related to muscle mass regulation in CKD mice. RNAseq analysis was performed on the gastrocnemius muscle. Ingenuity Pathway Analysis revealed that the top 12 differentially expressed genes in CKD were correlated with impaired muscle and neuron regeneration, enhanced muscle thermogenesis and fibrosis. Importantly, vitamin D repletion normalized the expression of those 12 genes in CKD mice. Vitamin D repletion may be an effective therapeutic strategy for adipose tissue browning and muscle wasting in CKD patients.

Cholecalciferol or Calcifediol in the Management of Vitamin D Deficiency.

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.

Canadian recommendations for vitamin D intake for persons affected by multiple sclerosis.

In 2016, the Multiple Sclerosis (MS) Society of Canada convened a panel of expert scientists, clinicians and patient advocate to review the evidence for an association between vitamin D status and MS prevention and/or disease modification. The goal was to develop clear and accurate recommendations on optimal vitamin D intake and status for people affected by MS for use in clinical practice and public health policy. The final consensus report was based on a review and grading of existing published papers combined with expert opinions of panel members. The report led to recommendations published in November of 2018 on the website of the MS Society of Canada, one in a format for use by health professionals and another in a question and answer format that was targeted to persons affected by MS and the general public. For people at risk of developing MS, the vitamin D recommendations are similar to those for the general public following the Dietary Reference Intakes (DRI) for Canada and the United States. Adults should achieve and maintain a normal vitamin D status with monitoring by physicians (serum 25-hydroxyvitamin D (25(OH)D) = 50-125 nmol/L, requiring 600-4000 IU vitamin D/d intake). For pregnant women, newborn infants, and all youth at risk of MS, vitamin D intakes should also follow DRI recommendations but additionally their serum 25-(OH)D should be monitored. For persons living with MS, existing evidence did not allow prediction of a vitamin D intake that might modify MS disease course. For this group the recommendations included: (1) serum 25-(OH)D should be maintained in the range of 50-125 nmol/L (600-4000 IU/d intake).; and (2) vitamin D should not be used as a standalone treatment for MS. For children and adolescents, serum 25OHD status was recommended to be measured upon diagnosis of a first clinical demyelinating event, and monitored every 6 months to achieve a target of 75 nmol/L Since people living with MS are at increased risk of osteoporosis, falls, and bone fractures, it was recommended to achieve a minimum serum 25OHD concentration that is protective for bone health in the general population. The revision of the MS Society recommendations on vitamin D awaits future clinical trial evidence.

Vitamin D, menopause, and aging: quo vadis?

Menopause and aging are associated with changes in circulating gonadal steroid hormones, insulin sensitivity, body composition, and also lifestyle and social coordinates. Vitamin D status influences different metabolic adjustments, aside from calcium-phosphorus and bone metabolism. The main blood marker used to measure endogenous vitamin D status is 25-hydroxyvitamin D. Aging is associated with increases in serum parathyroid hormone and alkaline phosphatase, and a decrease of serum calcium, phosphorus, and vitamin D metabolites. 25-Hydroxyvitamin D status is also influenced by the circannual rhythm of sun irradiation. Results of clinical association studies have not correlated with intervention trials, experimental studies, and/or meta-analyses regarding the role of vitamin D on different outcomes in women during their second half of life and the vitamin D supplementation dose needed to improve clinical endpoints. Discordant results have been related to the method used to measure vitamin D, the studied population (i.e., sociodemographics and ethnicity), study designs, and biases of analyses. Vitamin D supplementation with cholecalciferol or calcifediol may improve some metabolic variables and clinical outcomes in young postmenopausal and older women. Studies seem to suggest that calcifediol may have some advantages over other forms of vitamin D supplementation. Further studies are needed to define interventions with supplements and effective food fortification.

Evaluating extended-release calcifediol as a treatment option for chronic kidney disease-mineral and bone disorder (CKD-MBD).

Introduction: Extended-release calcifediol (ERC) is an orally administered prohormone of active vitamin D (1,25-dihydroxyvitamin D [1,25D]) designed to safely and sufficiently increase serum total 25-hydroxyvitamin D (25D) to reduce elevated parathyroid hormone (PTH) in patients with non-dialysis-chronic kidney disease (ND-CKD). ERC is currently approved in the United States and Canada.Areas covered: Herein, key clinical data relating to the pharmacokinetics, pharmacodynamics, efficacy and safety of ERC are reviewed.Expert opinion: Currently available treatment options for secondary hyperparathyroidism (SHPT) in ND-CKD have limitations: the effectiveness of nutritional vitamin D supplements for reduction of PTH levels is unproven and active (1α-hydroxylated) vitamin D analogues elevate serum calcium, which increases the risk of hypercalcemia and vascular calcification. Clinical studies show that ERC is an effective, well tolerated treatment for SHPT in ND-CKD. ERC gradually raises serum 25D levels, resulting in physiologically regulated increases in serum 1,25D and sustained reductions in PTH, while avoiding clinically meaningful increases in serum phosphorus, calcium and fibroblast growth factor 23. ERC offers a new, effective and well tolerated treatment option for the early management of SHPT in patients with ND-CKD.

Osteomalacia in subtropical Auckland.

A 56-year-old man was referred with left-sided hip pain. MRI scans demonstrated an undisplaced stress fracture in the femoral neck and subchondral oedema within the femoral head. Bone densitometry showed T-scores of -2.0 at the spine, -3.5 at the femoral neck and -2.4 for the total hip. Laboratory tests revealed 25-hydroxyvitamin D <10 nmol/L. He was prescribed a 10-day course of calciferol 1.25 mg (50 000 IU)/day and started on calcium carbonate 1.25 g twice daily. Following the correction of vitamin D deficiency, his symptoms resolved. A striking feature of this patient was the complete reversal of 'osteoporosis' within 14 months with vitamin D and calcium supplementation. Bone mineral densities (BMDs) increased by 19.5% and 33.4% at the spine and hip, respectively. Such changes are never seen with conventional pharmacological management of osteoporosis. Vitamin D deficiency should be considered as a cause for reduced BMD in people with risk factors.

Questioning the Safety of Calcidiol in Hemodialysis Patients.

BACKGROUND: Epidemiological studies have suggested a survival benefit for hemodialysis patients on paricalcitol or calcitriol, but nutritional vitamin D supplementation of patients already on vitamin D receptor (VDR) activators is controversial. METHODS: This observational retrospective cohort study was conducted with prospectively collected data from all consecutive patients with chronic kidney disease (CKD) who underwent hemodialysis under routine clinical practice conditions for two years. RESULTS: Of the 129 patients, 89 were treated with calcidiol, paricalcitol, and/or calcitriol. The patients with any vitamin D formulation had higher serum concentrations of 25-hydroxy vitamin D and fibroblast growth factor-23 and tended to have higher mortality rates (42% vs. 25%, p = 0.07). On subgroup analysis, any calcidiol treatment or calcidiol combined with paricalcitol associated with significantly higher mortality rates than no treatment (47% and 62.5%, p = 0.043 and 0.008, respectively). The association between calcidiol/paricalcitol treatment and elevated mortality remained significant after adjusting for age, sex, diabetes, C-reactive protein, and hemodialysis vintage. Any calcidiol and calcidiol/paricalcitol treatment exhibited a dose-response relationship with mortality (p for trend: 0.002 and 0.005, respectively). CONCLUSIONS: These data draw attention to the hitherto unexplored safety of calcidiol supplementation in patients on hemodialysis, especially in those already on vitamin D. Until clinical trials demonstrate the safety and efficacy of this approach, caution should be exercised when prescribing these patients ≥0.5 calcidiol mg/month.

Hypovitaminosis D: Is It Time to Consider the Use of Calcifediol?

Hypovitaminosis D is becoming a notable health problem worldwide. A consensus exists among several different medical societies as to the need for adequate levels of vitamin D for bone and general health. The correct method by which to restore normal vitamin D levels is still a matter of debate. Although cholecalciferol remains the most commonly distributed form of vitamin D supplementation worldwide, several drugs with vitamin D activity are available for clinical use, and making the correct selection for the individual patient may be challenging. In this narrative review, we aim to contribute to the current knowledge base on the possible and appropriate use of calcifediol-the 25-alpha-hydroxylated metabolite-in relation to its chemical characteristics, its biological properties, and its pathophysiological aspects. Furthermore, we examine the trials that have aimed to evaluate the effect of calcifediol on the restoration of normal vitamin D levels. Calcifediol is more soluble than cholecalciferol in organic solvents, due to its high polarity. Good intestinal absorption and high affinity for the vitamin-D-binding protein positively affect the bioavailability of calcifediol compared with cholecalciferol. In particular, orally administered calcifediol shows a much shorter half-life than oral cholecalciferol. Most findings suggest that oral calcifediol is about three- to five-fold more powerful than oral cholecalciferol, and that it has a higher rate of intestinal absorption. Accordingly, calcifediol can be particularly useful in treating diseases associated with decreased intestinal absorption, as well as obesity (given its lower trapping in the adipose tissue) and potentially neurological diseases treated with drugs that interfere with the hepatic cytochrome P-450 enzyme system, resulting in decreased synthesis of calcifediol. Up to now, there has not been enough clinical evidence for its use in the context of osteoporosis treatment.

Vitamin D C3-epimer levels are proportionally higher with oral vitamin D supplementation compared to ultraviolet irradiation of skin in mice but not humans.

A proportion of circulating 25-hydroxy vitamin D3 (25(OH)D3)) undergoes epimerization to form C3-epi 25(OH)D3 and C3-epi 1,25(OH)2D3. These epimers have less calcaemic activity than non-epimerized metabolites and are not differentiated by many immunoassays when reporting total 25(OH)D3 levels. This study aimed to compare the effect of exposure to ultraviolet radiation (UVR) and oral vitamin D3 supplementation on vitamin D C3-epimer levels. C57Bl/6 female mice were fed either vitamin D-sufficient (vitamin D3 2000 IU/kg) or -deficient diets (no vitamin D3) for 4 weeks. Among the vitamin D-deficient group, the shaved backs of half were irradiated daily for 4 days with 1 kJ/m2 UVR, followed by twice weekly irradiation for 4 weeks. Despite similar 25(OH)D3 levels, the UV-irradiated group had a lower proportion of C3-epi 25(OH)D3 at week 7 (p < 0.05) and week 9 (p < 0.01). C3-epimer concentrations and %C3-epi 25(OH)D3 were also analysed in serum samples from two human clinical trials. These trials investigated the effect of high dose oral vitamin D3 supplementation and narrowband UVB phototherapy, respectively. Serum 25(OH)D3 and the %C3-epi 25(OH)D3 levels measured at 12 months after oral vitamin D3 supplementation were not significantly different to those measured at the time of maximal effect of phototherapy (2 months). Thus, the proportion of 25(OH)D3 that undergoes epimerization is greater with oral vitamin D3 supplementation than exposure to UVR in mice, but not in humans. This important difference between human and murine vitamin D metabolism warrants consideration when interpreting animal studies.

Native vitamin D in pre-dialysis chronic kidney disease.

Chronic kidney disease patients have a high prevalence of vitamin D insufficiency/deficiency. Vitamin D deficiency has been associated with a variety of bone, metabolic and cardiovascular disorders. However, the role of native vitamin D supplementation (ergocalciferol, cholecalciferol or calcifediol) remains unclear in chronic kidney disease (CKD), particularly in the pre-dialytic phase. Several international guidelines have been developed on CKD-Mineral and Bone Disorder, but the optimal strategy for native vitamin D supplementation and its clinical benefit remains a subject of debate in the scientific community. This paper aims to review the available literature, including randomized clinical trials that evaluated the effects of native vitamin D supplementation on pre-dialysis CKD on biochemical and clinically relevant outcomes.

Effects of alendronate and calcifediol compared to alendronate and cholecalciferol in osteoporotic patients.

BACKGROUND: Several formulations of vitamin D and alendronate are available for the treatment of osteoporosis. The objective of this study was to examine efficacy and safety of calcifediol (25(OH)D) compared to cholecalciferol (vitamin D3) and also the relationship between different formulations of alendronate and adverse reactions. METHODS: We observed a population of women diagnosed with postmenopausal osteoporosis or osteopenia treated with alendronate 70 mg weekly associated to vitamin D3 or 25(OH)D at monthly total dose of 625 µg. Data collected both at baseline (T0) and at follow-up after at least 12 months of therapy (T1) were: demographic characteristics, BMI, full medical history, lumbar T-score, femur T-score, calcium, osteocalcin, alkaline phosphatase, PTH and vitamin D blood level. RESULTS: A total of 362 patients were enrolled in the study. Alendronate 70 mg + calcifediol (A+25(OH)D) group consisted of 202 patients while 160 patients were treated with alendronate 70 mg + cholecalciferol (A+D3). In the A+25(OH)D group, we observed a significant increase in lumbar T-score value (0.26±0.35 vs. 0.13±0.3) and serum vitamin D (20.64±20.71 vs. 6.07±7.61 ng/mL) levels compared to the A+D3 group (P<0.05). The lowest incidence of gastrointestinal adverse reactions was observed among patients taking alendronate 70 mg in drinkable solution form (P<0.05). CONCLUSIONS: Alendronate 70 mg with calcifediol gives a better outcome in the treatment of osteoporosis according to lumbar T-score and vitamin D serum level observed at one-year follow-up compared to alendronate 70 mg with cholecalciferol. Both vitamin D formulations did not show to cause hypercalcemia in this study. Alendronate 70 mg in drinkable solution form is also associated with lowest incidence of gastrointestinal adverse reactions.