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.

Associations between vitamin D levels and periodontal attachment loss.

OBJECTIVES: Periodontitis is accompanied by attachment loss and alveolar bone resorption. Vitamin D (VD) deficiency was closely associated with bone loss or osteoporosis. The study aims to investigate the potential relationship between different VD levels and severe periodontal attachment loss in American adults. METHODS: A cross-sectional analysis was conducted including 5749 participants in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2014. The association of periodontal attachment loss progression with total VD, vitamin D3 (VD3), and vitamin D2 (VD2) levels was assessed using multivariable linear regression models, hierarchical regression, fitted smoothing curves, and generalized additive models. RESULTS: Based on the indicators of 5749 subjects, we found that severe attachment loss tended to occur in the elderly or males and was accompanied by less total VD levels, or VD3 levels, as well as a lower poverty-income ratio (PIR). Total VD (below the inflection point: 111 nmol/L) or VD3 were negatively associated with the progression of attachment loss in each multivariable regression model. In threshold analysis, VD3 is linearly correlated with the progression of attachment loss (ß = - 0.0183, 95% CI: - 0.0230 to - 0.0136). The relationship between VD2 and attachment loss progression was an S-shaped curve (inflection point: 5.07 nmol/L). CONCLUSION: Increasing total VD (below 111 nmol/L) and VD3 levels may be beneficial to periodontal health. VD2 levels above 5.07 nmol/L were a risk factor for severe periodontitis. CLINICAL RELEVANCE: The present study reports that different vitamin D levels may serve as different associations with periodontal attachment loss progression.

Effect of supplementation of vitamin D3 or vitamin D2 on serum concentrations of free and total 25-hydroxyvitamin D and the expression of genes involved in immune function in peripheral blood mononuclear cells of weaned pigs.

The present study aimed to compare the effects of vitamin D2 and vitamin D3 supplementation on concentrations of total and free 25(OH)D in plasma and the expression of genes involved in the innate immune system in peripheral blood mononuclear cells (PBMC) in weaned pigs. Five groups of pigs (with an initial body weight of around 9 kg) received basal diets supplemented with either 500 (control group), 1000 or 2000 IU vitamin D3/kg diet or 1000 or 2000 IU vitamin D2/kg diet for a period of 4 weeks. Vitamin D supplementation did not influence feed intake, body weight gain, feed conversion ratio, apparent total tract digestibility of calcium and phosphorus, and serum concentrations of calcium, inorganic phosphate and parathyroid hormone. Supplementation of vitamin D3 led to a dose-dependent increase of the concentrations of total and free 25(OH)D in serum. In contrast, pigs supplemented with 1000 or 2000 IU vitamin D2/kg diet did not have higher concentrations of total and free 25(OH)D in serum than the control group. The ratio of free/total 25(OH)D in serum was not influenced by vitamin D3 supplementation, whereas the group supplemented with 2000 IU vitamin D2/kg diet had a higher free/total 25(OH)D ratio than the groups supplemented with 1000 or 2000 IU vitamin D3/kg diet. Genes involved in vitamin D signalling (CYP27B1, VDR), as well as pro-inflammatory and immune regulatory genes (TLR4, TNF, IL1B and TGFB1) and genes encoding porcine protegrins (NPG1, NPG4), proteins belonging to the group of antimicrobial peptides, in PBMC were not different among groups supplemented with vitamin D3 or vitamin D2 and the control group. Therefore, the study indicates that supplementation of vitamin D2 causes much lower levels of total 25(OH)D than supplementation of vitamin D3 and that supplementation of vitamins D2 or D3 at moderate levels does not have an impact on the innate immune function in healthy pigs.

Implementation strategies for improving vitamin D status and increasing vitamin D intake in the UK: current controversies and future perspectives: proceedings of the 2nd Rank Prize Funds Forum on vitamin D.

A multi-disciplinary expert group met to discuss vitamin D deficiency in the UK and strategies for improving population intakes and status. Changes to UK Government advice since the 1st Rank Forum on Vitamin D (2009) were discussed, including rationale for setting a reference nutrient intake (10 µg/d; 400 IU/d) for adults and children (4+ years). Current UK data show inadequate intakes among all age groups and high prevalence of low vitamin D status among specific groups (e.g. pregnant women and adolescent males/females). Evidence of widespread deficiency within some minority ethnic groups, resulting in nutritional rickets (particularly among Black and South Asian infants), raised particular concern. Latest data indicate that UK population vitamin D intakes and status reamain relatively unchanged since Government recommendations changed in 2016. Vitamin D food fortification was discussed as a potential strategy to increase population intakes. Data from dose-response and dietary modelling studies indicate dairy products, bread, hens' eggs and some meats as potential fortification vehicles. Vitamin D3 appears more effective than vitamin D2 for raising serum 25-hydroxyvitamin D concentration, which has implications for choice of fortificant. Other considerations for successful fortification strategies include: (i) need for 'real-world' cost information for use in modelling work; (ii) supportive food legislation; (iii) improved consumer and health professional understanding of vitamin D's importance; (iv) clinical consequences of inadequate vitamin D status and (v) consistent communication of Government advice across health/social care professions, and via the food industry. These areas urgently require further research to enable universal improvement in vitamin D intakes and status in the UK population.

Development of a two-dimensional liquid chromatography-tandem mass-spectrometry method for the determination of vitamin D2 in mushrooms.

Different foods, especially mushrooms, are a valuable source of vitamin D2. However, published concentrations in mushrooms show large variabilities. One reason for this is certainly the high biological variability caused by growth conditions, and another could also be found in the analytical methodology. Therefore, this study aimed to develop a sensitive and highly selective two-dimensional liquid chromatography mass spectrometry (LC-MS/MS) method for vitamin D2 analysis in mushrooms. After validation, the method was applied to four different mushroom species. The developed method with a one-step extraction procedure showed a limit of detection of 0.01 µg vitamin D2/g dry mass (DM), a limit of quantification of 0.05 µg vitamin D2/g DM, and recovery rates between 87.6 and 94.8%. The total run time including the re-equilibration of the columns for the next injection was 7.5 min. After adding increased concentrations of pure substance to Pleurotus ostreatus, Lentinula edodes, and brown and white button mushrooms the standard addition plot showed excellent correlation coefficients (R2) of > 0.9994. Mean vitamin D2 concentrations were observed at 0.122 ± 0.007, 0.074 ± 0.005, 0.099 ± 0.007, and 0.073 ± 0.005 µg/g DM. The coefficient of variation (CV) was between 5.1 and 7.6%. This well-optimized, sensitive LC-MS/MS method, with a fast and simple sample preparation and a short run time, can be applied to future studies especially in different mushroom species with variable growing conditions. This will improve our knowledge about the vitamin D2 content in mushrooms.

UVB-exposed wheat germ oil increases serum 25-hydroxyvitamin D2 without improving overall vitamin D status: a randomized controlled trial.

PURPOSE: This study investigated whether UVB-exposed wheat germ oil (WGO) is capable to improving the vitamin D status in healthy volunteers. METHODS: A randomized controlled human-intervention trial in parallel design was conducted in Jena (Germany) between February and April. Ultimately, 46 healthy males and females with low mean 25-hydroxyvitamin D (25(OH)D) levels (34.9 ± 10.6 nmol/L) were randomized into three groups receiving either no WGO oil (control, n = 14), 10 g non-exposed WGO per day (- UVB WGO, n = 16) or 10 g WGO, which was exposed for 10 min to ultraviolet B-light (UVB, intensity 500-630 µW/cm2) and provided 23.7 µg vitamin D (22.9 µg vitamin D2 and 0.89 µg vitamin D3) (+ UVB WGO, n = 16) for 6 weeks. Blood was obtained at baseline, after 3 and 6 weeks and analyzed for serum vitamin D-metabolite concentrations via LC-MS/MS. RESULTS: Participants who received the UVB-exposed WGO were characterized by an increase of circulating 25(OH)D2 after 3 and 6 weeks of intervention. However, the 25(OH)D3 concentrations decreased in the + UVB WGO group, while they increased in the control groups. Finally, the total 25(OH)D concentration (25(OH)D2 + 25(OH)D3) in the + UVB WGO group was lower than that of the non-WGO receiving control group after 6 weeks of treatment. In contrast, circulating vitamin D (vitamin D2 + vitamin D3) was higher in the + UVB WGO group than in the control group receiving no WGO. CONCLUSION: UVB-exposed WGO containing 23.7 µg vitamin D can increase 25(OH)D2 levels but do no improve total serum levels of 25(OH)D of vitamin D-insufficient subjects. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03499327 (registered, April 13, 2018).

Vitamin D metabolites, D3 and D2, and their independent associations with depression symptoms among adults in the United States.

Background: The two metabolites of vitamin D; serum 25-hydroxyvitamin D3 (25(OH)D3) and D2 (25(OH)D2), and their independent roles in mood regulation are unexplored. This study aims to examine 25(OH)D3 and 25(OH)D2 and their interplay with depression symptoms.Materials and Methods: Utilizing data from the U.S. National Health and Nutrition Examination Survey (2007-2011, 2013-2014), a cross-sectional study was conducted. Depression was assessed using the 9-item Patient Health Questionnaire, and those with total score ≥5 were considered as having mild to severe depression symptoms. 25(OH)D3 and 25(OH)D2, the clinical markers of vitamins D3 and D2, were measured. Weighted logistic regressions were utilized to examine the adjusted association between 25(OH)D3 and depression, and the effect modification of 25(OH)D2.Results: The sample included 11,471 participants aged 20-80 years. Of those, 23.4% reported symptoms of depression, 28.9% had 25(OH)D3 deficiencies(<20 ng/mL), and 21.5% exhibited presence of 25(OH)D2(>0.6 ng/mL). After adjustment, among participants with presence of 25(OH)D2, those who had 25(OH)D3 deficiencies were more likely by 54% to report depression symptoms (OR = 1.54,95%CI:1.14-2.07). In fact, among participants with nearly no 25(OH)D2 presence, a significant effect estimate between 25(OH)D3 deficiency and depression symptom was not observed(OR = 1.11,95%CI:0.94-1.31).Conclusions: Both vitamin D metabolites retain an independent and significant role in mood regulation. The study provides valuable insights on vitamin D3 and its significant relationship with depression symptoms in the presence of vitamin D2. Further research is required to elucidate the distinct mechanisms of these two vitamin D metabolites on depression.

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.

Impacts of deficiency in vitamin D derivatives on disease severity in adult bronchial asthma patients.

Vitamin D affects innate and adaptive immunity processes that impact treatment, severity, and morbidity of acute asthma episodes. Several vitamin D forms may help modulate immunity, including vitamin D2 (D2), vitamin D3 (D3), 25-hydroxyvitamin D3 (25(OH)D3), and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). This study assessed serum levels of vitamin D derivatives in bronchial asthma patients and their correlation with disease markers. One hundred thirteen subjects, divided into two groups, were enrolled. The first group included 73 asthmatic patients (57 males and 16 females), and the second included 40 healthy adults (31 males and 9 females) as a control group. All subjects were evaluated with a careful history and clinical examination, a chest X-ray with a posteroanterior view, routine laboratory examination, spirometry, and asthma control tests (ACT). Vitamin D serum levels were assessed using ultra-performance liquid chromatography (UPLC) with tandem mass spectrometry. Disease markers were assessed and correlated with serum levels of vitamin D forms. Markers included forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC%, peak expiratory flow (PEF), forced expiratory flow25-75% (FEF25-75%), eosinophilic blood count, and total immunoglobulin E (IgE). Asthmatic patients had significantly lower serum levels of vitamin D than healthy controls (p ≤ 0.001). Further, serum vitamin D levels decreased significantly in uncontrolled asthmatic patients than partially controlled and controlled patients. Correlations for 25(OH)D3 and 1,25-(OH) 2D3 were stronger than for D2 and D3. There were negative correlations for eosinophilic blood count, total IgE, and ACT. Serum levels of all vitamin D forms were reduced in asthmatic patients with moderate to strong correlations with disease severity. Vitamin D deficiency or even insufficiency may thus play a role in disease severity.

Serum 25-hydroxyvitamin D response to vitamin D supplementation in infants: a systematic review and meta-analysis of clinical intervention trials.

PURPOSE: For the prevention of nutritional rickets, 400 IU vitamin D daily and circulating 25-hydroxyvitamin D (25OHD) concentrations > 50 nmol/L are recommended, whereas the toxicity threshold is set at 250 nmol/L. We synthesized the evidence for the effect of vitamin D supplementation on incremental 25OHD in infants up to 1 year of age. METHODS: We performed a systematic review and meta-analysis of intervention trials in several databases. A total of 87 records were identified for full-text review and 27 articles with 61 studies were included in the final analysis. RESULTS: The selected 61 studies included 1828 participants. Nineteen cohorts had already mean baseline 25OHD levels ≥ 50 nmol/L. The weighted mean difference in 25OHD following vitamin D supplementation was + 49.4 nmol/L (95% CI 43.6-55.3 nmol/L; P < 0.001). The increment was dose-dependent (P = 0.002), was higher in full-term than in pre-term infants (P < 0.001), was higher in infants with baseline 25OHD < 50 nmol/L as compared to ≥ 50 nmol/L (P = 0.001), and was marginally influenced by the 25OHD test procedure (P = 0.080). Vitamin D3 doses of 400 IU/day were sufficient to achieve 25OHD concentrations ≥ 50 nmol/L in most full-term infants. A 25OHD level of 250 nmol/L was not exceeded in ≥ 97.5% of infants at doses between 200 and 1200 IU/day, but potentially in ≥ 2.5% of infants at a dose of 1600 IU/day. CONCLUSIONS: Vitamin D supplementation of 400 IU/day is sufficient for achieving 25OHD concentrations able to prevent nutritional rickets. A more personalized vitamin D dosing strategy would require 25OHD testing, but also assay standardization.

Association of vitamin D2 and D3 with type 2 diabetes complications.

AIMS: Vitamin D measurement is a composite of vitamin D2 (25(OH)D2) and D3 (25(OH)D3) levels, and its deficiency is associated with the development of type 2 diabetes (T2DM) and diabetic complications; vitamin D deficiency may be treated with vitamin D2 supplements. This study was undertaken to determine if vitamin D2 and D3 levels differed between those with and without T2DM in this Middle Eastern population, and the relationship between diabetic microvascular complications and vitamin D2 and vitamin D3 levels in subjects with T2DM. METHODS: Four hundred ninety-six Qatari subjects, 274 with and 222 without T2DM participated in the study. Plasma levels of total vitamin D2 and D3 were measured by LC-MS/MS analysis. RESULTS: All subjects were taking vitamin D2 and none were taking D3 supplements. Vitamin D2 levels were higher in diabetics, particularly in females, and higher levels were associated with hypertension and dyslipidemia in the diabetic subjects (p < 0.001), but were not related to diabetic retinopathy or nephropathy. Vitamin D3 levels measured in the same subjects were lower in diabetics, particularly in females (p < 0.001), were unrelated to dyslipidemia or hypertension, but were associated with retinopathy (p < 0.014). Neither vitamin D2 nor vitamin D3 were associated with neuropathy. For those subjects with hypertension, dyslipidemia, retinopathy or neuropathy, comparison of highest with lowest tertiles for vitamin D2 and vitamin D3 showed no difference. CONCLUSIONS: In this Qatari cohort, vitamin D2 was associated with hypertension and dyslipidemia, whilst vitamin D3 levels were associated with diabetic retinopathy. Vitamin D2 levels were higher, whilst vitamin D3 were lower in diabetics and females, likely due to ingestion of vitamin D2 supplements.

UV induced conversion during drying of ergosterol to vitamin D in various mushrooms: Effect of different drying conditions.

BACKGROUND: Mushrooms are increasingly popular around the world as a nutritional food which is an excellent source of vitamin D2. Although natural mushrooms often contain very little vitamin D2 as many are grown in the dark, they are rich in ergosterol, a precursor to vitamin D2. Ergosterol can be converted to vitamin D2 under ultraviolet radiation. Due to the high water content of fresh mushroom, its quality deteriorates rapidly after harvest, and drying is the most commonly used technology to extend the shelf life. The vitamin D2 content of dried mushrooms depends on the drying conditions used. SCOPE AND APPROACH: In this review, the chemistry of the photo-conversion process of ergosterol to vitamin D2 under ultraviolet radiation is introduced. The ergosterol and vitamin D contents in different mushroom varieties are discussed. The effects of several drying methods and the influence of different drying conditions are reviewed.Key findings and conclusions: Thermal drying in the presence of UV has been proven to convert ergosterol into vitamin D and enhance the nutritional content of all types of edible mushrooms. Solar drying, hot air drying, freeze drying, microwave drying and infrared drying can be used for mushrooms drying under selected operating conditions. A critical evaluation of published literature demonstrates the importance of applying appropriate drying methodology to maximize the nutritional value of various types of edible mushrooms.

Synthesis, CYP24A1-Dependent Metabolism and Antiproliferative Potential against Colorectal Cancer Cells of 1,25-Dihydroxyvitamin D2 Derivatives Modified at the Side Chain and the A-Ring.

Experimental data indicate that low-calcemic vitamin D derivatives (VDDs) exhibit anticancer properties, both in vitro and in vivo. In our search for a vitamin D analog as potential anticancer agent, we investigated the influence of chirality in the side chain of the derivatives of 1,25-dihydroxyergocalciferol (1,25D2) on their activities. In this study, we synthesized modified analogs at the side chain and the A-ring, which differed from one another in their absolute configuration at C-24, namely (24S)- and (24R)-1,25-dihydroxy-19-nor-20a-homo-ergocalciferols (PRI-5105 and PRI-5106, respectively), and evaluated their activity. Unexpectedly, despite introducing double-point modifications, both analogs served as very good substrates for the vitamin D-hydroxylating enzyme. Irrespective of their absolute C-24 configuration, PRI-5105 and PRI-5106 showed relatively low resistance to CYP24A1-dependent metabolic deactivation. Additionally, both VDDs revealed a similar antiproliferative activity against HT-29 colorectal cancer cells which was higher than that of 1,25D3, the major biologically active metabolite of vitamin D. Furthermore, PRI-5105 and PRI-5106 significantly enhanced the cell growth-inhibitory activity of 5-fluorouracil on HT-29 cell line. In conclusion, although the two derivatives showed a relatively high anticancer potential, they exhibited undesired high metabolic conversion.

[Determination of 25-hydroxyl vitamin D in serum by isotope dilution ultra-fast liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To establish a rapid and accurate method for determination of 25-hydroxyl vitamin D2, 25-hydroxyl vitamin D3 and 3-epi-25-hydroxyl vitamin D3 in serum by isotope dilution ultra-fast liquid chromatography-tandem mass spectrometry(UFLC-MS/MS). METHODS: The serum sample was extracted by nhexane after methanol/acetonitrile precipitation protein, and then the extract was concentrated by nitrogen and volumed with the primary mobile phase. The chromatographic separation was carried out on a Phenomenex Kinetex F5 column(2. 1 mm × 150 mm, 1. 7 µm) by using 0. 1%(V/V) formic acid and 0. 1%(V/V) formic acid/methanol solution as the mobile phase with the gradient elution. Detection was performed in positive multi-reaction monitoring(MRM) mode with the isotope internal labeling method for quantification. RESULTS: The baseline separation was obtained within 6 min for the epimer 25-hydroxyl vitamin D3 and 3-epi-25-hydroxyl vitamin D3, and the accurate qualification was obtained for the simultaneous determination of 25-hydroxyl vitamin D2, 25-hydroxyl vitamin D3 and 3-epi-25-hydroxyl vitamin D3. The three analytes showed good linear relationship within the range of 0. 5-50. 0 µg/L with a correlation coefficient r >0. 9995. The limits of detection(LODs) and the limits of quantitation(LOQs) of the method were 0. 15 µg/L and 0. 5 µg/L, respectively. The recoveries of the method were84. 3%-109. 0%(n = 11) at the three spiked levels of 1. 0, 10. 0 and 30. 0 µg/L, and the relative standard deviations(RSDs) were between 0. 8%-6. 8%. At the same time, the certified standard reference materials(SRM) of the America National Institute of Standards and Technology(NIST) Level 1, Level 2, Level 3 and Level 4(SRM 972 a)were used as the quality control samples for verification, the relative deviations of the measurement result were less than 5% compared with the reference values. CONCLUSION: The developed method has the characteristics of simplicity, rapidity, sensitivity and accuracy, and is suitable for the simultaneous rapid determination of 25-hydroxyl vitamin D2, 25-hydroxyl vitamin D3 and 3-epi-25-hydroxyl vitamin D3 in serum.

Is calcifediol better than cholecalciferol for vitamin D supplementation?

Modest and even severe vitamin D deficiency is widely prevalent around the world. There is consensus that a good vitamin D status is necessary for bone and general health. Similarly, a better vitamin D status is essential for optimal efficacy of antiresorptive treatments. Supplementation of food with vitamin D or using vitamin D supplements is the most widely used strategy to improve the vitamin status. Cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) are the most widely used compounds and the relative use of both products depends on historical or practical reasons. Oral intake of calcifediol (25OHD3) rather than vitamin D itself should also be considered for oral supplementation. We reviewed all publications dealing with a comparison of oral cholecalciferol with oral calcifediol as to define the relative efficacy of both compounds for improving the vitamin D status. First, oral calcifediol results in a more rapid increase in serum 25OHD compared to oral cholecalciferol. Second, oral calcifediol is more potent than cholecalciferol, so that lower dosages are needed. Based on the results of nine RCTs comparing physiologic doses of oral cholecalciferol with oral calcifediol, calcifediol was 3.2-fold more potent than oral cholecalciferol. Indeed, when using dosages ≤ 25 µg/day, serum 25OHD increased by 1.5 ± 0.9 nmol/l for each 1 µg cholecalciferol, whereas this was 4.8 ± 1.2 nmol/l for oral calcifediol. Third, oral calcifediol has a higher rate of intestinal absorption and this may have important advantages in case of decreased intestinal absorption capacity due to a variety of diseases. A potential additional advantage of oral calcifediol is a linear dose-response curve, irrespective of baseline serum 25OHD, whereas the rise in serum 25OHD is lower after oral cholecalciferol, when baseline serum 25OHD is higher. Finally, intermittent intake of calcifediol results in fairly stable serum 25OHD compared with greater fluctuations after intermittent oral cholecalciferol.

The effect of vitamin D2 supplementation on muscle strength in early postmenopausal women: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Low serum 25-hydroxyvitamin D [25(OH)D] has been shown to be associated with low muscle mass and loss of muscle strength, resulting in increased disability and frailty in older men and women. Vitamin D deficiency is common in postmenopausal women. The primary objective of the present study was to evaluate the effects of vitamin D supplementation on muscle strength in early postmenopausal women. The effects of vitamin D2 supplementation on muscle mass and muscle cross-sectional area (CSA) were secondarily investigated. METHODS: A 12-week, prospective, randomized, double-blind, placebo-controlled trial was conducted in early postmenopausal women (45-60 years old) with vitamin D deficiency (serum 25(OH)D < 20 ng/ml). A total of 88 subjects were randomized into group I: vitamin D2 supplement 40 000 IU/week (n = 44), or group II: placebo (n = 44). Serum 25(OH)D level, muscle strength, muscle mass and muscle CSA were assessed at baseline and 12 weeks after the supplementation. RESULTS: After 12 weeks of supplementation, 70% of women in group I achieved a sufficient level of serum 25(OH)D (>30 ng/ml). There were significant differences in changes of serum 25(OH)D levels between the two groups (p < 0.05). Muscle strength and muscle CSA in group I increased significantly after 12 weeks (p = 0.015, 0.045, respectively). However, there were no significant differences in the mean changes of muscle strength, muscle mass and muscle CSA between the two groups (p = 0.16, 0.89, 0.84, respectively). CONCLUSION: In this study, we found no obvious effect of vitamin D supplementation on the changes in muscle strength, muscle mass and muscle CSA when compared to placebo. However, there were significant changes in muscle strength and muscle CSA from baseline in the vitamin D supplementation group.

Enrichment of vitamin D2 in mycelium from submerged cultures of the agaric mushroom Pleurotus sapidus.

Ergosterol, a precursor of vitamin D2, is present in the cell membrane of all fungi. It can be transformed into vitamin D2 by UV-B exposure. In this study, a basidiomycete, Pleurotus sapidus, cultivated in liquid malt extract medium was exposed to UV-B light. In addition, autoclaved, abiotic mycelium was put through UV-B exposure for the first time. The effects of different UV-B exposure times, surface areas and temperatures on vitamin D2 formation were analyzed. The conversion of ergosterol to vitamin D2 at ambient temperature almost reached completion within 10 min resulting in vitamin D2 concentrations of 365 µg (g dry matter)-1. Prolonged exposure of the biotic mycelium for up to 60 min resulted in a reduced vitamin D2 concentration with stagnation at about 280 µg (g dry matter)-1. Exposure of the abiotic mycelium showed a slower increase but also leveled off at the same concentration. Furthermore, it could be shown that vitamin D2 formation depends on the temperature and the exposed surface area. The vitamin D2 concentration augmented after increasing the exposed surface from 65.0 to 298.6 cm2. The ergosterol content of P. sapidus was analyzed in a way similar to vitamin D2 and resulted in 3.75 ± 0.06 mg (g dry matter)-1 ergosterol.

Production of an active form of vitamin D2 by genetically engineered CYP105A1.

Our previous studies revealed that CYP105A1 can convert vitamin D3 (VD3) to its active form, 1α,25-dihydroxyvitamin D3 (1,25D3). Site-directed mutagenesis of CYP105A1 based on its crystal structure dramatically enhanced its activity; the activity of double variants R73A/R84A and R73A/R84V was more than 100-fold higher than that of the wild type of CYP105A1. In contrast, these variants had a low ability to convert vitamin D2 (VD2) to 1α,25-dihydroxyvitamin D2 (1,25D2), whereas they catalyzed the sequential hydroxylation at positions C25 and C26 to produce 25,26D2. A comparison of the docking models of 25D2 and 25D3 into the substrate-binding pocket of R73A/R84A suggests that the side chain of the Met239 inhibits the binding of 25D2 for 1α-hydroxylation. Therefore, the Met239 residue of R73A/R84A was substituted for Ala. As expected, the triple variant R73A/R84A/M239A showed a 22-fold higher 1α-hydroxylation activity towards 25D2. To the best of our knowledge, this is the first report on the generation of microbial cytochrome P450 that converts VD2 to 1,25D2 via 25D2.

The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention.

Vitamin D deficiency and insufficiency is a global health issue that afflicts more than one billion children and adults worldwide. The consequences of vitamin D deficiency cannot be under estimated. There has been an association of vitamin D deficiency with a myriad of acute and chronic illnesses including preeclampsia, childhood dental caries, periodontitis, autoimmune disorders, infectious diseases, cardiovascular disease, deadly cancers, type 2 diabetes and neurological disorders. This review is to put into perspective the controversy surrounding the definition for vitamin D deficiency and insufficiency as well as providing guidance for how to treat and prevent vitamin D deficiency.

Model-based meta-analysis for comparing Vitamin D2 and D3 parent-metabolite pharmacokinetics.

Association of Vitamin D (D3 & D2) and its 25OHD metabolite (25OHD3 & 25OHD2) exposures with various diseases is an active research area. D3 and D2 dose-equivalency and each form's ability to raise 25OHD concentrations are not well-defined. The current work describes a population pharmacokinetic (PK) model for D2 and 25OHD2 and the use of a previously developed D3-25OHD3 PK model [1] for comparing D3 and D2-related exposures. Public-source D2 and 25OHD2 PK data in healthy or osteoporotic populations, including 17 studies representing 278 individuals (15 individual-level and 18 arm-level units), were selected using search criteria in PUBMED. Data included oral, single and multiple D2 doses (400-100,000 IU/d). Nonlinear mixed effects models were developed simultaneously for D2 and 25OHD2 PK (NONMEM v7.2) by considering 1- and 2-compartment models with linear or nonlinear clearance. Unit-level random effects and residual errors were weighted by arm sample size. Model simulations compared 25OHD exposures, following repeated D2 and D3 oral administration across typical dosing and baseline ranges. D2 parent and metabolite were each described by 2-compartment models with numerous parameter estimates shared with the D3-25OHD3 model [1]. Notably, parent D2 was eliminated (converted to 25OHD) through a first-order clearance whereas the previously published D3 model [1] included a saturable non-linear clearance. Similar to 25OHD3 PK model results [1], 25OHD2 was eliminated by a first-order clearance, which was almost twice as fast as the former. Simulations at lower baselines, following lower equivalent doses, indicated that D3 was more effective than D2 at raising 25OHD concentrations. Due to saturation of D3 clearance, however, at higher doses or baselines, the probability of D2 surpassing D3's ability to raise 25OHD concentrations increased substantially. Since 25OHD concentrations generally surpassed 75 nmol/L at these higher baselines by 3 months, there would be no expected clinical difference in the two forms.