Optimisation of vitamin D status in global populations.

Vitamin D is important for musculoskeletal health. Concentrations of 25-hydroxyvitamin D, the most commonly measured metabolite, vary markedly around the world and are influenced by many factors including sun exposure, skin pigmentation, covering, season and supplement use. Whilst overt vitamin D deficiency with biochemical consequences presents an increased risk of severe sequelae such as rickets, osteomalacia or cardiomyopathy and usually warrants prompt replacement treatment, the role of vitamin D supplementation in the population presents a different set of considerations. Here the issue is to keep, on average, the population at a level whereby the risk of adverse health outcomes in the population is minimised. This position paper, which complements recently published work from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, addresses key considerations regarding vitamin D assessment and intervention from the population perspective. This position paper, on behalf of the International Osteoporosis Foundation Vitamin D Working Group, summarises the burden and possible amelioration of vitamin D deficiency in global populations. It addresses key issues including screening, supplementation and food fortification.

The effect of vitamin D2 on lipid profile, anthropometric indices, blood pressure, and inflammatory and glycemic biomarkers in humans: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Even though the role of D2 (ergocalciferol) on cardiovascular disease risk components has been studied, conflicting results have been reported. Moreover, no single study has studied all these parameters and the role of vitamin D2 individually has not been assessed; hence, this systematic review and meta-analysis of randomized controlled trials was conducted to assess the effect of vitamin D2 supplementation on lipid profile, anthropometric indices, blood pressure, and inflammatory and glycemic biomarkers in humans. METHODS: Web of Science, Scopus, PubMed/Medline, and Embase were searched from database inception to July 2024, and the random effects model, according to the DerSimonian and Laird method, was used to generate combined estimates of the intervention's effect on the outcomes. RESULTS: After full-text analysis, 11 eligible articles were included in our meta-analyses. No statistically significant association was observed between vitamin D2 administration and BMI, WC, TC, HDL-C, LDL-C, TG, DBP or SBP; however, a statistically significant decrease in CRP (WMD: - 1.92 mg/dL, 95 % CI: - 3.30 to - 0.54, P = 0.006) and HbA1c levels (WMD: - 0.37 %, 95 % CI: - 0.66 to - 0.09, P = 0.009), and a non-statistically significant decrease in FBG (WMD: - 4.61 mg/dL, 95 % CI: - 14.71 to 5.47, P = 0.370, I2 = 90 %, P ˂ 0.001) and HOMA-IR (WMD: - 0.10, 95 % CI: - 0.17-0.03, P = 0.002) were detected. CONCLUSION: In summary, our systematic review and meta-analysis discovered that vitamin D2 administration was associated with a statistically significant decrease in CRP and HbA1c levels, without a significant correlation with other outcomes.

Efficacy of vitamin D2 in maintaining serum total vitamin D concentrations and bone mineralisation in adult dogs fed a plant-based (vegan) diet in a 3-month randomised trial.

Dogs are considered omnivores based on their evolution consuming diets including animal tissue. Few feeding trials evaluating the nutritional suitability of exclusively plant-based (vegan) diets in dogs have been published, and the efficacy of vitamin D2 in maintaining canine serum vitamin D levels has not been clearly determined. A blinded dietary trial included sixty-one healthy desexed adult dogs: thirty-one fed an experimental extruded vegan diet (PLANT) and thirty fed a commercial extruded meat-based diet (MEAT) for 3 months. Dogs were screened via veterinary examination and routine laboratory analyses prior to enrolment, at baseline and exit timepoints. Body composition was measured by dual-energy X-ray absorptiometry and blood was collected for vitamin D profiling. All dogs maintained health parameters, body weight and composition throughout the study. Dogs maintained on PLANT demonstrated a significant reduction in platelet count, creatinine, blood urea nitrogen and cholesterol, though values remained within normal reference ranges. Dogs fed PLANT also demonstrated a shift from vitamin D3 to vitamin D2 metabolites, though total vitamin D analogue levels were unchanged, with the exception of 24,25-dihydroxyvitamin D. Bone mineral content and density did not differ from baseline values. Health status was maintained in dogs fed PLANT and vitamin D2 appeared efficacious in maintaining serum total vitamin D concentrations and bone mineralisation. Findings support the hypothesis that PLANT was comparable to MEAT for maintenance of healthy adult dogs for at least 3 months and identified areas where further research is warranted to elucidate the potential risks and benefits of plant-based (vegan) diets.

Structural diversification of vitamin D using microbial biotransformations.

Vitamin D deficiencies are linked to multiple human diseases. Optimizing its synthesis, physicochemical properties, and delivery systems while minimizing side effects is of clinical relevance and is of great medical and industrial interest. Biotechnological techniques may render new modified forms of vitamin D that may exhibit improved absorption, stability, or targeted physiological effects. Novel modified vitamin D derivatives hold promise for developing future therapeutic approaches and addressing specific health concerns related to vitamin D deficiency or impaired metabolism, such as avoiding hypercalcemic effects. Identifying and engineering key enzymes and biosynthetic pathways involved, as well as developing efficient cultures, are therefore of outmost importance and subject of intense research. Moreover, we elaborate on the critical role that microbial bioconversions might play in the a la carte design, synthesis, and production of novel, more efficient, and safer forms of vitamin D and its analogs. In summary, the novelty of this work resides in the detailed description of the physiological, medical, biochemical, and epidemiological aspects of vitamin D supplementation and the steps towards the enhanced and simplified industrial production of this family of bioactives relying on microbial enzymes. KEY POINTS: • Liver or kidney pathologies may hamper vitamin D biosynthesis • Actinomycetes are able to carry out 1α- or 25-hydroxylation on vitamin D precursors.

The impact of vitamin D administration on mortality in COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Vitamin D, known for its role in bone health, is now being explored for its immunomodulatory effects. This study aimed to evaluate the impact of vitamin D supplementation on mortality in coronavirus disease 2019 (COVID-19) patients through a systematic review and meta-analysis of randomized controlled trials. METHODS: A comprehensive search was conducted across PubMed, Scopus, Web of Science, and preprint servers for eligible trials up to July 8, 2024. Two investigators independently screened the records and assessed the risk of bias using the Cochrane Risk of Bias Tool. Trials were eligible if they compared vitamin D with control interventions in adults with COVID-19. Data extraction and analysis were carried out independently, employing a random-effects model to estimate pooled odds ratios for mortality. RESULTS: Nineteen randomized controlled trials with 2495 participants were included. The meta-analysis showed a significant reduction in all-cause mortality with vitamin D supplementation (pooled OR 0.72, 95% CI 0.53-0.98; I2 = 20%). Subgroup analysis for severe COVID-19 cases also indicated significant mortality reduction (pooled OR 0.57, 95% CI 0.35-0.92; I2 = 18%). CONCLUSION: Vitamin D supplementation appears to reduce mortality in COVID-19 patients, especially in severe cases. These findings highlight the potential benefits of vitamin D as an adjunct treatment in COVID-19, though further large-scale trials are needed to confirm these effects and determine optimal dosing.

Low 25 (OH) vitamin D levels are associated with increased prevalence of nonalcoholic fatty liver disease and significant liver fibrosis.

AIMS: Evidence on the role of 25-Hydroxyvitamin D (25(OH)D) in the occurrence and progression of nonalcoholic fatty liver disease (NAFLD) is conflicting and population-based data are scarce. Here, we assess the association between 25(OH)D levels, NAFLD and liver fibrosis in the general population. MATERIALS AND METHODS: This is an analysis of data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey. We included adult participants with available data on vibration-controlled transient elastography (VCTE) and without viral hepatitis and significant alcohol consumption. Steatosis and fibrosis were diagnosed by the median values of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. 25(OH)D was measured by high performance liquid chromatography-tandem mass spectrometry. RESULTS: A total of 3970 participants (1928 men and 2042 women) were included in the study. The prevalence of NAFLD (CAP ≥ 274 dB/m) and significant liver fibrosis (LSM ≥ 8 kPa) were 41.7% (95% CI 39.4-44.0) and 8.4% (95% CI 7.0-9.9), respectively, while 21.1% (95% CI 17.3-25.4) of participants had low 25(OH)D levels (<50 nmol/L). A multivariable logistic regression model adjusted for age, sex, race-ethnicity, body mass index, waist circumference, calendar period, diabetes, chronic kidney disease, and vitamin D supplementation showed that compared with participants with low 25(OH)D, those with optimal levels (≥75 nmol/L) had lower odds of both NAFLD (OR 0.73, 95% CI 0.55-0.98 p = 0.038) and significant liver fibrosis (OR 0.65, 95% CI 0.44-0.96, p = 0.033). CONCLUSIONS: An inverse relationship was found between 25(OH)D and NAFLD and fibrosis, suggesting a possible role of vitamin D in NAFLD occurrence and progression.

Vitamin D: sources, physiological role, biokinetics, deficiency, therapeutic use, toxicity, and overview of analytical methods for detection of vitamin D and its metabolites.

Vitamin D has a well-known role in the calcium homeostasis associated with the maintenance of healthy bones. It increases the efficiency of the intestinal absorption of dietary calcium, reduces calcium losses in urine, and mobilizes calcium stored in the skeleton. However, vitamin D receptors are present ubiquitously in the human body and indeed, vitamin D has a plethora of non-calcemic functions. In contrast to most vitamins, sufficient vitamin D can be synthesized in human skin. However, its production can be markedly decreased due to factors such as clothing, sunscreens, intentional avoidance of the direct sunlight, or the high latitude of the residence. Indeed, more than one billion people worldwide are vitamin D deficient, and the deficiency is frequently undiagnosed. The chronic deficiency is not only associated with rickets/osteomalacia/osteoporosis but it is also linked to a higher risk of hypertension, type 1 diabetes, multiple sclerosis, or cancer. Supplementation of vitamin D may be hence beneficial, but the intake of vitamin D should be under the supervision of health professionals because overdosing leads to intoxication with severe health consequences. For monitoring vitamin D, several analytical methods are employed, and their advantages and disadvantages are discussed in detail in this review.

Effectiveness of vitamin D2 supplementation on high-sensitivity C-reactive protein and other metabolic indices in menopausal Thai women: a randomized-controlled trial.

OBJECTIVE: To investigate the effectiveness of vitamin D2 supplementation with ergocalciferol on high-sensitivity C-reactive protein (hsCRP) level and other cardio-metabolic indices in menopausal Thai women. MATERIALS AND METHODS: A double-blind, randomized, placebo-controlled trial was conducted at the menopause clinic of a university hospital in Thailand from May 2017 to 2018. Participants were 80 postmenopausal women randomly assigned to treatment (N = 40, receiving vitamin D2 40,000 IU/week) or control (N = 40, receiving placebo) for 12 weeks. The primary outcome was hsCRP level, and secondary outcomes were cardio-metabolic profiles and 10-year risk of developing cardiovascular disease using the Framingham risk score. The changes from baseline to week-12 (Δ) of all outcomes were analyzed using a modified intention-to-treat (ITT) population. RESULTS: The vitamin D2 (N = 39) and placebo (N = 37) groups were comparable in all baseline characteristics. The hsCRP level was significantly reduced in the vitamin D2 group (Δ of -0.39 ± 1.30 mg/L, p = .024) but not in the placebo group (Δ of -0.15 ± 1.15 mg/L, p = .521). However, the Δ of hsCRP had no statistical difference between groups; neither did the Δ of other cardio-metabolic parameters. CONCLUSION: In menopausal Thai women, vitamin D2 supplementation with ergocalciferol 40,000 IU/week for 12 weeks can reduce hsCRP level; and the treatment might be superior to placebo. However, the hsCRP levels after 12 weeks between both groups were not statistically different. Clinical Trial Registration: Thai Clinical Trials Registry (TCTR20161216001).

SYNOPSISVitamin D2 supplementation in menopausal Thai women can reduce hsCRP level and might be superior to placebo.

Vitamin D and tension-type headache: causal association or epiphenomenon?

Background-Purpose: Low serum vitamin D (VD) has been already associated with a series of highly prevalent pain-related conditions, including fibromyalgia, migraine and chronic widespread pain. Considering the potential interplay between VD and pain signalling pathways, the association of VD with tension-type headache (TTH) was reviewed.Methods: A multifaceted narrative approach assessing the relationship of serum VD with TTH and TTH parameters, as well as the efficacy of VD supplementation for the prevention of TTH, was fostered. MEDLINE, CENTRAL and EMBASE were comprehensively searched for this purpose, while Google Scholar was also explored according to a structured approach. ClinicalTrials.gov and European Union Clinical Trials Register were explored for ongoing prevention trials.Results: Although available evidence was suggestive of an association between VD and TTH, mainly of the chronic type, the causal nature of the association remains to be determined. Considering the lack of longitudinal evidence, this relationship could arguably reflect behavioural patterns of headache sufferers. On the other hand, evidence principally originated from tertiary clinical settings (severe comorbidity burden) and researchers tend to report a concomitant association of both entities with generalized musculoskeletal compromise. In this context, the association between TTH and VD may represent nothing more than a secondary by-product of the simultaneous relationship of other comorbid diseases-conditions with both TTH and low serum VD. Regarding its efficacious properties, only one ongoing trial specifically designed to explore the efficacy of VD in chronic TTH in adults was retrieved.Conclusions: There is no evidenced based indication for VD supplementation in TTH.

Improving vitamin D status in bariatric surgery subjects with monthly high-dose ergocalciferol.

Background: Vitamin D insufficiency is common before and after bariatric surgery. Optimal supplementation to treat vitamin D insufficiency is not clearly defined. Objective: Determine if serum 25 (OH) D levels improve by the consumption of an additional monthly ergocalciferol supplement by subjects after bariatric surgery. Study design: Thirty-two subjects were randomly divided to receive an additional 100,000 IUs of ergocalciferol monthly after bariatric surgery (n=10) or standard level vitamin D supplement after bariatric surgery (n=22). Serum 25 (OH) D, calcium, and hemoglobin A1c levels were measured preoperatively and one year after bariatric surgery. Results: Mean changes in BMI at 1-year post-operation was -18.12±6.46 kg/m2 in the control group versus -18.84±4.7 kg/m2; p=0.638 in the vitamin D group. One year after bariatric surgery, the mean changes from baseline in vitamin D levels were 2.69±9.4 and 12.4±17.0 ng/mL in control and intervention groups, respectively. The treated group showed a marginally higher mean increase in Vitamin D than the control group, p=0.059. Other mean changes at 1-year post-surgery that were not significantly different include calcium -0.264±0.45 and -0.21±0.509 mg/dl in control and intervention groups, respectively and HbA1c -1.0±1.21 and -0.95±0.071% in control and intervention groups, respectively. Conclusion: This study showed 100,000 IUs ergocalciferol once a month is a safe and effective treatment for vitamin D insufficiency in most patients having bariatric surgery.

Effectiveness of vitamin D2 compared with vitamin D3 replacement therapy in a primary healthcare setting: a retrospective cohort study.

INTRODUCTION: Vitamin D deficiency is a worldwide public health concern, which can lead to severe diseases, such as rickets in children and osteomalacia in adults. Most studies have compared equimolar unit-to-unit doses of vitamin D2 and D3. OBJECTIVES: The current study aimed to answer the research question: "How effective is vitamin D2 (600,000 U/1.5 ml) compared to vitamin D3 (300,000 U/1 ml) parenteral supplementation for raising serum vitamin D levels in adult patients treated in a primary health care setting?" SETTING: Primary Health Care Corporation (PHCC) runs 28 health centers distributed throughout the State of Qatar and its capital city, Doha. Qatar is on the east coast of the Arabic peninsula, with very hot and sunny summers and a desert climate. STUDY DESIGN: This was a retrospective observational cohort study. METHOD: A total of 15,716 participants were recruited following ethical approval. They were identified by electronic medical records (EMR) describing the clinical encounters of individuals aged 18 to 60-years-old who attended a health center operated by the PHCC during the 3.5-year study period from January 1, 2017 to June 30, 2020. The PHCC EMR system uses SNOMED codes (a systematically organized computer-processable collection of medical terms providing codes, names, synonyms, and definitions implemented for clinical documentation and reporting). Four study groups were created depending on the type of vitamin D injection and the oral form of replacement therapy. The analysis scheme used the serum vitamin D level within the preceding 4 weeks (pretreatment), followed by administration of the treatment dose. The post-treatment serum testing value should have been available within a maximum of 12 weeks. The Statistical Package for Social Sciences (IBMSPSS; IBM Corp., Armonk, NY, USA) version 23 software was used for the statistical analysis. RESULTS: Four treatment options were compared, including a vitamin D2 injection, a vitamin D3 injection, combined use of a vitamin D2 injection + a D2 tablet, and combined use of a vitamin D3 injection + a D2 tablet. All four treatment groups were associated with a statistically significant increase in serum vitamin D within a maximum of 12 weeks of follow-up. The vitamin D2 injection alone was associated with the lowest increase in serum concentration by a mean of 3.2 ng/ml. In contrast, the vitamin D3 injection alone or with a D2 tablet increased serum vitamin D by 6.1 and 5.6 ng/ml, respectively. Using the combination of a vitamin D2 injection and a tablet only added a marginal increase of 2.3 ng/ml in serum vitamin D on top of the 3.2 ng/ml increase attained after administering the D2 injection alone. CONCLUSION: Utilizing vitamin D3 in an injectable form is the best choice to restore severe vitamin D deficiency. Furthermore, it was superior to the injectable form of vitamin D2, even though vitamin D2 has double the molar units.

High-dose versus low-dose ergocalciferol for correcting hypovitaminosis D after fragility hip fracture: a randomized controlled trial.

BACKGROUND: Hypovitaminosis D can be observed in most fragility hip fracture patients. However, measurement of 25-hydroxyvitamin D (25(OH)D) level is costly and may not be available in some centers. Without the baseline serum 25(OH)D level, the appropriate dose of vitamin D supplementation is not known. The aim of this study was to evaluate the effectiveness and safety of vitamin D supplementation in fragility hip fracture patients compared between high- and low-dose vitamin D supplementation. METHODS: A total of 140 patients diagnosed with fragility hip fracture were randomly allocated to either the high-dose (60,000 IU/week) or low-dose (20,000 IU/week) vitamin D2 supplementation group for 12 weeks. The number of patients who achieved optimal vitamin D level (serum 25(OH)D > 30 ng/mL), the proportion of patients who developed hypercalcemia, and the functional outcome were compared between groups. RESULTS: Of the 140 patients who were enrolled, 21 patients were lost to follow-up during the study period. The remaining 119 patients (58 and 61 in the high- and low-dose groups, respectively) were included in the final analysis. The high-dose group had a higher rate of serum 25(OH)D restoration to optimal level than the low-dose group (82.8% vs 52.5%, respectively; p < 0.001). Approximately 3.4 and 1.6% of patients in the high- and low-dose groups, respectively, had mild transient hypercalcemia, but none developed moderate, severe, or symptomatic hypercalcemia. There were no differences in functional outcome scores between groups. CONCLUSIONS: In treatment settings where baseline serum 25(OH)D level can't be evaluated in older adults with fragility hip fracture, we recommend high-dose vitamin D2 of approximately 60,000 IU/week for 12 weeks, with subsequent switch to a maintenance dose. This regimen effectively restored serum vitamin D to an optimal level in 82.8% of patients without causing symptomatic hypercalcemia. TRIAL REGISTRATION: The protocol of this study was retrospectively registered in the Thai Clinical Trials Registry database no. TCTR20180302007 on 20 February 2018.

Use of Fortified Bread for Addressing Vitamin D Deficiency.

Vitamin D deficiency due to inadequate sun exposure and/or inadequate intake from food is very common worldwide, consisting a major public health problem. As prolonged exposure to ultraviolet radiation involves risks, food fortification of staple foods emerges as a favorable solution for addressing vitamin D deficiency. Bread is a suitable candidate for fortification as it is consumed often and is the main carbohydrate source in European countries.The purpose of this study was the evaluation of the bioavailability of vitamin D from a fortified Greek-type bread that was developed as a means for addressing vitamin D deficiency, by comparing the absorption curve of vitamin D in fortified bread in relation to that of plain vitamin supplementation. Two groups of clinically healthy volunteers consumed 25,000 international units (IU) of vitamin D3 (cholecalciferol) either in fortified bread (Group A) or in a plain supplement form (Group B). The baseline plasma concentrations of cholecalciferol were 8.1 ± 6.0 ng/mL and 6.8 ± 3.4 ng/mL in Groups A and B, respectively. After 12, 24, and 48 h, the concentrations of cholecalciferol in Group A were 16.7 ± 4.8, 15.3 ± 8.3 and 11.9 ± 6.0 ng/mL, respectively, and in Group B, 15.2 ± 3.3, 11.6 ± 2.4, and 9.6 ± 3.6 ng/mL, respectively. In both groups, the concentrations of cholecalciferol at 12 and 24 h were significantly higher than the baseline concentrations (p < 0.01). There were no statistically significant differences between the concentrations of cholecalciferol between Groups A and B, at each time point.Cholecalciferol is bioavailable from Greek-type fortified bread and bread could be used for addressing vitamin D deficiency.

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.

Effectiveness of intramuscular ergocalciferol treatment in a patient with osteomalacia and insufficiency fractures due to severe vitamin D deficiency after bariatric surgery.

Vitamin D (vitD) deficiency and bone loss may occur after bariatric surgery and hence, supplementation with high oral doses of vitD may be required. Alternatively, intramuscular depot ergocalciferol, which slowly releases vitD and bypasses the gastrointestinal tract, could be administrated. We present a case of severe vitD deficiency-osteomalacia after gastric bypass operation for morbid obesity, treated with ergocalciferol intramuscularly. A 45-year-old woman was presented with hip pain and muscle weakness, which led ultimately to immobilization in a wheelchair. Fifteen years ago, she underwent roux-en-Y gastric by-pass for morbid obesity. Occasionally, she was treated with multivitamin supplements. On admission, iron deficiency anaemia, vitD deficiency (25OHD: 3.7 ng/ml) and secondary hyperparathyroidism were revealed. Bone turnover markers (BTM) were elevated. Radiological evaluation demonstrated insufficiency fractures on the pubic and left femur and reduced BMD. Osteomalacia due to vitD deficiency and calcium malabsorption were diagnosed. Calcium citrate 500 mg qid and intramuscular ergocalciferol 600,000 IU every 20 days were initiated. One month later, musculoskeletal pain and weakness were resolved and the patient was mobilized. Few months later, vitD, BTM and BMD showed substantial improvement. Intramuscular ergocalciferol administration can improve the clinical and biochemical status and thus, is suggested to prevent and/or treat osteomalacia in such patients.

A randomized double-blinded placebo controlled trial of ergocalciferol 40,000 versus 100,000 IU per week for vitamin D inadequacy in institutionalized postmenopausal women.

BACKGROUND: Vitamin D inadequacy is common in institutionalized post-menopausal women who are at the highest risk for osteoporotic fracture. AIM: To evaluate efficacy and safety of ergocalciferol 40,000 versus 100,000 IU per week for 12 weeks for vitamin D inadequacy in institutionalized postmenopausal women. METHOD: A randomized double-blinded placebo-controlled trial was conducted in 94 institutionalized subjects with baseline 25(OH)D levels < 30 ng/mL. Subjects were randomized to receive ergocalciferol 40,000 (standard dose) or ergocalciferol 100,000 IU (high dose) per week. Serum 25(OH)D levels, calcium, phosphate, handgrip strength, time up and go (TUG) test and quality of life by EQ-5D-5L were measured at baseline and 12 weeks after randomization. RESULTS: Of the 94 subjects enrolled, 85 subjects completed the study. Subjects in the high dose group had higher mean 25(OH)D levels than subjects in the standard group (51.73 ± 19.35 and 34.5 ± 9.12, p < 0.001). More subjects in the high dose group (90.9%) achieved optimal 25(OH)D levels (> 30 ng/mL) than those in the standard group (65.9%), p = 0.007. In a subgroup analysis of subjects with vitamin D deficiency (< 20 ng/mL, n = 44) and severe vitamin D deficiency (< 10 ng/mL, n = 9), more subjects in the high dose group achieved optimal 25(OH)D levels than those in the standard group (88% and 100% versus 47.4% and 16.7% with p of 0.007 and 0.018, respectively). There were no differences in handgrip strength, TUG, EQ-5D-5L and adverse events between groups. DISCUSSION/CONCLUSIONS: Subjects who received high dose ergocalciferol achieved more optimal 25(OH)D levels than those who received standard dose. High dose ergocalciferol is preferred to optimize 25(OH)D levels in subjects with severe vitamin D deficiency.

[Method Verification for Vitamin D Analysis in Processed Foods Based on the Analytical Manual for the Standard Tables of Food Composition in Japan 2015 (Seventh Revised Edition)].

Considerable amounts of processed foods contain vitamin D (ergocalciferol (D2) and cholecalciferol (D3)) as food additives. For field surveys on food additives, the analytical method for vitamin D should be well-validated. However, the current official method in Japan cannot separately determine the concentrations of D2 and D3, whereas the method for the Standard Tables of Food Composition in Japan 2015 (STFC method) can. Therefore, in this study, we verified the applicability of the STFC method to processed foods. During the course of this research, we added some improvements to the original method. Spike and recovery experiments using vegetable juice, soymilk, and corn flakes as food matrices showed that the recovery rates (relative standard deviation) of D2 and D3 were 103-112% (4.7-12.6%) and 102-109% (2.4-21.8%), respectively, at the estimated method limit of quantification (EMLOQ) level; and 100-110% (4.0-7.4%) and 102-105% (3.8-4.8%), respectively, at 10 times the EMLOQ level. These results indicated that accuracy and precision of the modified STFC method were enough to determine dietary D2 and D3 as endogenous nutrients and/or food additives, and suggested that this method is appropriate for analyzing vitamin D concentrations in processed foods.

Vitamin-D2 treatment-associated decrease in 25(OH)D3 level is a reciprocal phenomenon: a randomized controlled trial.

BACKGROUND: Vitamin-D2 (D2) treatment has been associated with a decrease in 25-hydroxy (25(OH)) vitamin-D3 (D3) level, suggesting that D3 treatment would be preferred to raise total 25(OH) vitamin-D (D) level. We postulated that D2 treatment-associated decrease in 25(OH)D3 level is related to the increase in 25(OH)D level rather than being D2-specific, and thus there would be a similar D3 treatment-associated decrease in 25(OH)D2 level. METHODS: Fifty volunteers were block-randomized to 50,000 IU D2 or placebo orally once (study-1) and fifty volunteers received 50,000 IU D2 orally once and 4 days later block-randomized to 50,000 IU D3 or placebo orally once (study-2). Interventions were concealed from volunteers and research coordinators and blindly-administered. Serum 25(OH)D2 and 25(OH)D3 levels were blindly-determined at baseline and days 14, 28, 42, and 56, post-randomization by high performance liquid chromatography assay. Results of 97 participants were analyzed. Primary outcome measure was day-28 D2-associated change in 25(OH)D3 level in study-1 and D3-associated change in 25(OH)D2 level in study-2, adjusted for baseline levels. RESULTS: Mean (95% confidence interval) difference between the active and placebo arms in the decrease in day-28 25(OH)D3 (study-1) and 25(OH)D2 (study-2) levels was 13.2 (9.7 to 16.6) and 9.8 (5.2 to 14.4) nmol/L, respectively. Corresponding differences at day-56 were 10.8 (6.8 to 14.8) and 1.7 (- 7.6 to 11.1) nmol/L, respectively. The difference between the placebo and active arms in area-under-the-curve at day-28 (AUC28) and day-56 (AUC56) were 262.3 (197.8 to 326.7) and 605.1 (446.3 to 784.0) for 25(OH)D3 (study-1) and 282.2 (111.2 to 453.3) and 431.2 (179.3 to 683.2) nmol.d/L for 25(OH)D2 (study-2), respectively. There were significant correlations between day-28 changes in 25(OH)D2 and 25(OH)D3 levels in study-1 (rho = - 0.79, p < 0.001) and study-2 (rho = - 0.36, p = 0.01), and between day-28 changes in 25(OH)D2 level and baseline 25(OH)D level in study-2 (rho = - 0.42, p = 0.003). CONCLUSIONS: Compared to placebo, D3 treatment is associated with a decrease in 25(OH)D2 level similar in magnitude to D2-treatment associated decrease in 25(OH)D3 level; however, the D3-placebo difference in 25(OH)D2 level is shorter-lasting. Changes in 25(OH)D2 and 25(OH)D3 levels are correlated with each other and with baseline 25 (OH) D levels, suggesting a common regulatory mechanism. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT03035084 (registered January 27, 2017).

Vitamin D and cardiovascular disease in chronic kidney disease.

Chronic kidney disease (CKD) is considered an independent risk factor for cardiovascular disease, with increased cardiovascular morbidity and mortality seen even in the early stages of CKD. Several studies have shown a high prevalence of vitamin D deficiency in individuals with CKD. Low vitamin D levels upregulate the renin-angiotensin-aldosterone system (RAAS), cause endothelial dysfunction, and increase inflammation. Epidemiological studies show an association between vitamin D deficiency and risk factors for cardiovascular disease, but a causal relationship has not been established. The high cardiovascular morbidity and mortality associated with CKD in adults requires therapies to decrease this elevated risk. However, results from several meta-analyses and randomized clinical trials in adults have not shown convincing evidence for the use of vitamin D therapy in improving cardiovascular outcomes. Lack of high-quality evidence from randomized clinical trials in children regarding the effectiveness and long-term safety of vitamin D treatment precludes any recommendations on its use to mitigate the cardiovascular burden of CKD.

Electrochemical Oxidation as a Tool for Generating Vitamin D Metabolites.

The electrochemical behavior of the vitamers cholecalciferol and ergocalciferol was investigated in order to determine whether it is possible to evaluate phase-I and phase-II metabolism of these steroids and yield metabolites that can serve as reference material. The vitamers were electrochemically-oxidized using an electrochemical system (ROXY™ EC system). The influence of pH value, solvent, and potential was evaluated. When using methanol or ethanol, the formation of artificial methoxy or ethoxy groups, respectively, was observed, while the use of acetonitrile did not show any formation of further functional groups. A neutral pH value and use of a constant potential led to the highest number of oxidation products with intensive signals. Additionally, a binding study between vitamin D and glucuronic acid as an example for phase-II conjugation was carried out. It was possible to detect adduct formation. Coupling mass spectrometry directly to electrochemistry (EC-MS) is a promising approach for generating vitamin D metabolites and/or yielding a number of metabolites without in vivo or in vitro test systems. It can support or even replace animal studies in the long-term and might be promising for yielding reference compounds.