Vitamin D3 supplementation in women practicing orthodox religious and intermittent fasting: A controlled study with formulation-specific effects

Vitamin D and insulin sensitivity: can gene association and pharmacogenetic studies of the vitamin D receptor provide clarity?

Four experiments were conducted to investigate the effects of varying concentrations of supplemental vitamin D3 on pig growth, feed preference, serum 25-hydroxycholecalciferol [25(OH)D3] , and bone mineralization of nursing and weanling pigs. In Exp. 1, 270 pigs (1.71 ± 0.01 kg BW) were administered 1 of 3 oral vitamin D3 dosages (none, 40,000, or 80,000 IU vitamin D3) on d 1 or 2 of age. Increasing oral vitamin D3 increased serum 25(OH)D3 on d 10 and 20 (quadratic, P < 0.01) and d 30 (linear, P < 0.01). No differences were observed in ADG before weaning or for nursery ADG, ADFI, or G:F. Vitamin D3 concentration had no effect on bone ash concentration or bone histological traits evaluated on d 19 or 35. In Exp. 2, 398 barrows (initially 7 d of age) were used in a 2 × 2 split plot design to determine the influence of vitamin D3 before (none or 40,000 IU vitamin D3 in an oral dose) or after weaning (1,378 or 13,780 IU vitamin D3/kg in nursery diets from d 21 to 31 of age) in a 45-d trial. Before weaning (7 to 21 d of age), oral vitamin D3 dose did not influence growth but increased (P < 0.01) serum 25(OH)D3 at weaning (d 21) and tended (P = 0.08) to increase 25(OH)D3 on d 31. Increasing dietary vitamin D3 concentration from d 21 to 31 increased (P < 0.01) serum 25(OH)D3 on d 31. Neither the oral vitamin D3 dose nor nursery vitamin D3 supplements influenced nursery ADG, ADFI, or G:F. In Exp. 3, 864 pigs (initially 21 d of age) were allotted to 1 of 2 water solubilized vitamin D3 treatments (none or 16,516 IU/L vitamin D3 provided in the drinking water from d 0 to 10) in a 30-d study. Providing vitamin D3 increased serum 25(OH)D3 concentrations on d 10, 20, and 30; however, vitamin D3 supplementation did not affect overall (d 0 to 30) ADG, ADFI, or G:F. In Exp. 4, 72 pigs were used in a feed preference study consisting of 2 feed preference comparisons. Pigs did not differentiate diets containing either 1,378 or 13,780 IU vitamin D3/kg but consumed less (P < 0.01) of a diet containing 44,100 IU vitamin D3/kg compared with the diet containing 1,378 IU vitamin D3/kg. Overall, these studies demonstrate that supplementing vitamin D3 above basal concentrations used in these studies is effective at increasing circulating 25(OH)D3, but the supplement did not influence growth or bone mineralization. Also, concentrations of vitamin D3 of 44,100 IU/kg of the diet may negatively affect feed preference of nursery pigs.

We evaluated the effectiveness of supplementation with high dose of oral vitamin D3 to correct vitamin D insufficiency. We have shown that one or two oral bolus of 300,000 IU of vitamin D3 can correct vitamin D insufficiency in 50% of patients and that the patients who benefited more from supplementation were those with the lowest baseline levels. Adherence with daily oral supplements of vitamin D3 is suboptimal. We evaluated the effectiveness of a single high dose of oral vitamin D3 (300,000 IU) to correct vitamin D insufficiency in a rheumatologic population. Over 1 month, 292 patients had levels of 25-OH vitamin D determined. Results were classified as: deficiency <10 ng/ml, insufficiency ≥10 to 30 ng/ml, and normal ≥30 ng/ml. We added a category using the IOM recommended cut-off of 20 ng/ml. Patients with deficient or normal levels were excluded, as well as patients already supplemented with vitamin D3. Selected patients (141) with vitamin D insufficiency (18.5 ng/ml (10.2-29.1) received a prescription for 300,000 IU of oral vitamin D3 and were asked to return after 3 (M3) and 6 months (M6). Patients still insufficient at M3 received a second prescription for 300,000 IU of oral vitamin D3. Relation between changes in 25-OH vitamin D between M3 and M0 and baseline values were assessed. Patients (124) had a blood test at M3. Two (2%) had deficiency (8.1 ng/ml (7.5-8.7)) and 50 (40%) normal results (36.7 ng/ml (30.5-5.5)). Seventy-two (58%) were insufficient (23.6 ng/ml (13.8-29.8)) and received a second prescription for 300,000 IU of oral vitamin D3. Of the 50/124 patients who had normal results at M3 and did not receive a second prescription, 36 (72%) had a test at M6. Seventeen (47%) had normal results (34.8 ng/ml (30.3-42.8)) and 19 (53%) were insufficient (25.6 ng/ml (15.2-29.9)). Of the 72/124 patients who receive a second prescription, 54 (75%) had a test at M6. Twenty-eight (52%) had insufficiency (23.2 ng/ml (12.8-28.7)) and 26 (48%) had normal results (33.8 ng/ml (30.0-43.7)). At M3, 84% patients achieved a 25-OH vitamin D level >20 ng/ml. The lowest the baseline value, the highest the change after 3 months (negative relation with a correlation coefficient r = -0.3, p = 0.0007). We have shown that one or two oral bolus of 300,000 IU of vitamin D3 can correct vitamin D insufficiency in 50% of patients.

Vitamin D plays a role in muscle function through genomic and non-genomic processes. The objective of this RCT was to determine the effect of monthly supplemental vitamin D3 onmuscle function in 70+ years old adults. Participants (n = 379) were randomized to receive, 12,000 IU, 24,000 IU or 48,000 IU of vitamin D3 monthly for 12 months. Standardized Hand Grip Strength (GS) and Timed-Up and Go (TUG) were measured before and after vitamin D3 supplementation. Fasting total plasma 25 hydroxyvitamin D (25OHD) and Parathyroid Hormone (PTH) concentrations were measured by Liquid Chromatography Tandem Mass Spectrometry (LC-MSMS) and immunoassay, respectively. Baseline plasma 25OHD concentrations were 41.3 (SD 19.9), 39.5 (SD 20.6), 38.9 (SD 19.7) nmol/L; GS values were 28.5 (SD 13.4), 28.8 (SD 13.0) and 28.1 (SD 12.1) kg and TUG test values were 10.8 (SD 2.5), 11.6 (SD 2.9) and 11.9 (SD 3.6) s for the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. Baseline plasma 25OHD concentration < 25 nmol/L was associated with lower GS (P = 0.003). Post-interventional plasma 25OHD concentrations increased to 55.9 (SD 15.6), 64.6 (SD15.3) and 79.0 (SD 15.1) nmol/L in the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively and there was a significant dose-related response in post-interventional plasma 25OHD concentration (p<0.0001). Post-interventional GS values were 24.1 (SD 10.1), 26.2 (SD10.6) and 25.7 (SD 9.4) kg and TUG test values were 11.5 (SD 2.6), 12.0 (SD 3.7) and 11.9 (SD 3.2) s for 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. The change (Δ) in GS and TUG from pre to post-intervention was not different between treatment groups before and after the adjustment for confounders, suggesting no effect of the intervention. Plasma 25OHD concentration was not associated with GS and TUG test after supplementation. In conclusion, plasma 25OHD concentration < 25 nmol/L was associated with lower GS at baseline. However, monthly vitamin D3 supplementation with 12,000 IU, 24,000 IU and 48,000 IU, for 12 months had no effect on muscle function in older adults aged 70+ years.Trial Registration : EudraCT 2011-004890-10 and ISRCTN35648481.

SummaryPoor adherence is a barrier to successful weight control. Intermittent energy restriction (IER) provides an alternative approach to those for whom daily energy restriction is not ideal. This study assessed changes in weight, body composition, and macronutrient intake for an IER and a continuous energy restriction (CONT) approach within a multicomponent weight management intervention. We randomized 35 adults with overweight/obesity (BMI = 31.2 ± 2.4 kg/m2) to CONT or IER for 24 weeks (12-week weight loss intervention and 12 weeks of weight loss maintenance). Diets were delivered within a multimodal weight management program including weekly group meetings with a registered dietitian, increased physical activity, and a comprehensive lifestyle change program. Retention and adherence were similar for CONT and IER. Weight, BMI, fat mass, percentage body fat, waist circumference, hip circumference, blood pressure, and heart rate all decreased after 24 weeks (all, P < .01), but there were no main effects of group (all, P > .27). Weight loss was clinically relevant in both CONT (11.38 ± 7.9%) and IER (9.37 ± 9.7%), and the proportion of each group achieving 5% weight loss was 82 and 61% (P = .16), respectively. Participant satisfaction was high in both groups. The results from this study (a) support the feasibility of IER as an alternative for weight loss and weight loss maintenance, (b) indicate that IER is an effective alternative to CONT for weight control and improvements in body composition, and (c) emphasize the importance of intensive lifestyle interventions with ongoing support for effective behaviour modification.

BackgroundPolycystic ovary syndrome (PCOS) is characterized by reproductive and endocrine abnormalities.ObjectiveThe present study aimed to assess the effect of oral contraceptive pills (OCPs) and vitamin D3 on sexual dysfunction in women with PCOS and vitamin D3 deficiency.Materials and methodsThis randomized double-blind placebo-controlled clinical trial was conducted in Iran between January and April 2019. The Female Sexual Function Index (FSFI) and Beck Depression Inventory (BDI) questionnaires were filled out for all participants and their serum levels of vitamin D3 were measured. Women with PCOS and vitamin D3 deficiency were divided into 2 equal groups (A and B) with a table of random numbers (n = 35/ each). Both groups were given vitamin D3 (50,000 IU/w) for 12 week. The case group was given low-dose OCP for 3 months and a similar placebo was given to the control group. Vitamin D3 level and sexual function were assessed in both groups at 3 and 6 months after taking OCP.ResultsThere was no statistically significant difference between the two groups in demographic characteristic such as weight (69.54 ± 10.34 vs 70.17 ± 10.60, P = 0.803). Both groups treated with vitamin D3 exhibited increased sexual function scores at the beginning of the study (P = 0.03) and 3 months (P = 0.01) after taking OCP. Examination of sexual function variables showed that sexual desire in the control group was greater than in the OCP-treated group at 3 (P = 0.009) and 6 (P = 0.01) months after entering the study.ConclusionThe results of the study showed that the score of women’s sexual performance increased in all areas, especially in the area of sexual desire, with the use of vitamin D3. The simultaneous use of OCP with vitamin D3 to improve sexual performance in these women had no significant difference with the use of vitamin D3 alone. According to the research findings, it is recommended that vitamin D3 supplementation can be used to increase the quality of life and improve sexual function in PCOS women.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00404-025-08159-4.

PurposeOutcomes investigating the effect of vitamin D3 (VD3) and omega-3 fatty acids (Omega-3FA) on serum estradiol (E2) are scarce and conflicting. No previous study has investigated the effect of VD3 combination with Omega-3FA on E2 levels. This study was designed to investigate the effect of VD3, Omega-3FA and VD3 plus Omega-3FA on serum E2 levels in premenopausal females diagnosed with vitamin D deficiency (VDD).Subjects and methodsThis randomized, placebo-controlled clinical trial was designed to evaluate the effects of 50,000 IU VD3 taken weekly, 300 mg Omega-3FA taken daily and their combination by the study participants for 8 weeks. The mid-follicular serum levels of E2 and 25-hydroxy vitamin D (25OHD) were assessed at 8 weeks. The study was conducted during winter on a convenience sample of healthy premenopausal Jordanian females with diagnosed VDD. Fasting serum levels for 25OHD and E2 were assessed at baseline and the end of the trial (after 8 weeks). Data were entered into SPSS and analyzed.ResultsHealthy premenopausal Jordanian females (N=86) with diagnosed VDD, mean age 32.8±8.9 years, were recruited into the study. Supplementation of VD3 alone resulted in a significant increase in serum 25OHD (13.4±7.9–28.2±7.1 ng/mL, P<0.001) and a significant decrease in E2 levels (85.7±16.5–60.3±20.6 pg/mL, P=0.001). Omega-3FA intake led to a significant decrease in serum 25OHD levels (21.2±12.8–13.6±9.2 ng/mL, P=0.001) and a significant increase in E2 levels (56.3±19.2–78.4±23.7 pg/mL, P=0.006). Combination therapy (VD3 plus Omega-3FA) resulted in a significant increase in both 25OHD (12.0±4.7–35.1±9.5 ng/mL, P<0.001) and E2 (43.0±23.4–57.3±31.5 pg/mL, P=0.028) levels.ConclusionResults of this study provide vital insight into the effects of D3, Omega-3FA and a combination of their supplementation on premenopausal Jordanian females with diagnosed VDD. Eight weeks of therapy led to decreased E2 level by VD3 and increased level by Omega-3FA supplementation. With regard to 25OHD, its level was increased by VD3 and decreased by Omega-3FA supplementation. Combination of VD3 plus Omega-3FA increased the levels of both E2 and 25OHD.Trial registrationThis trial was registered at clinicaltrials.gov as NCT03333564.

This cross-sectional observation study investigated the vitamin D (VD) status in Taiwanese pregnant women and the effects of VD supplementation and macronutrient intake on serum 25-hydroxy-vitamin D (25[OH]D) level. Data on VD intake, daily sunlight exposure, and carbohydrate intake were obtained from 125 pregnant women at 30–37 weeks’ gestation. Serum 25[OH]D level was measured before delivery in all enrolled women; and the mean 25(OH)D level was 43 nmol/L or 17.2 ng/mL. The 25(OH)D level was significantly correlated with total VD intake of pregnant women (r = 0.239; p = 0.007). The severe VD deficiency group (n = 16; mean of 25(OH)D level = 8.5 ng/mL) had significantly lower total VD intake and supplementation than the groups with VD deficiency (n = 69), insufficiency (n = 32), and sufficiency (n = 8). Those with ≥400 IU/day total VD intake (including VD from food and supplementation) had significantly higher 25(OH)D concentration than those with <400 IU/day total VD intake. Those with 400 IU/day VD supplementation could significantly increase serum 25(OH)D concentrations for pregnant women. Among 85 pregnant women with carbohydrate intake of ≥300 g/day, serum 25(OH)D levels were negatively correlated with carbohydrate intake (p = 0.031). In conclusion, VD deficiency was highly prevalent in Taiwanese pregnant women. VD supplementation was the most effective method for increasing 25(OH)D concentration in pregnant women. Higher carbohydrate intake might reduce 25(OH)D levels.

Background: The immune system (innate and adaptive) is influenced by vitamin D3, which affects gene expression and inflammatory pathways. An umbrella review was conducted to evaluate the power and accuracy of data connecting vitamin D3 to the outcomes of COVID-19 infection and to appraise the proof provided by published meta-analyses. Methods: MEDLINE, Embase, and the Cochrane Library were searched from database inception to 31 May 2022. Meta-analyses of prospective or retrospective observational studies and randomized trials were included. Evidence of association was graded according to the established criteria: strong, highly suggestive, suggestive, weak, or not significant. Results: From 74 publications, 27 meta-analyses described five associations between vitamin D3 levels and supplementation and COVID-19 outcomes. Low levels of vitamin D3 were significantly associated with severity (highly suggestive evidence; OR = 1.97 [95% CI, 1.55–2.51], p < 0.01; I2 = 77%, p < 0.01) and mortality risk due to COVID-19 disease (OR = 1.83 [95% CI, 1.55–2.16], p < 0.01; I2 = 50%, p < 0.01). Vitamin D3 supplementation, after a diagnosis of COVID-19 infection, was associated with significantly reduced infection severity (e.g., ICU admission) and mortality. Conclusions: This umbrella review of the available evidence suggests that insufficient vitamin D3 may increase COVID-19 infection risk, severity, and mortality, in addition to showing a highly suggestive association between vitamin D3 supplementation and reduced severity and mortality among infected patients.

Background There are limited randomized controlled trials of oral vitamin D supplementation in psoriasis, especially in Asia, and the results are inconclusive. Objective To investigate the clinical effect of oral vitamin D supplementation on psoriasis. Methods Patients with psoriasis were randomized to receive vitamin D2 60,000 IU or similar-looking placebo pills once every 2 weeks for 6 months. The primary outcome was improvement of the Psoriasis Area and Severity Index (PASI) score at 3 and 6 months after treatment. Serum levels of 25(OH)D, calcium, phosphate, parathyroid hormone, and C-reactive protein and adverse events were monitored. The chi-square test, Fisher's exact test, Student's t-test, and Spearman's correlation analysis were used in statistical analysis. Results Of 50 subjects screened, 45 were eligible and randomized to the oral vitamin D2 group (n=23) or placebo group (n=22). At enrollment, the mean PASI score was 4.45, and 26.7% of patients had vitamin D deficiency. At 3 months, the oral vitamin D2 group had significantly higher PASI improvement than the placebo group (mean PASI improvement: 1.43 versus [vs.] -0.33, p-value=0.034; mean %PASI improvement: 34.21% vs. -1.85%, p-value=0.039). The mean serum 25(OH)D level was significantly higher in the oral vitamin D group than in the placebo group (27.4 vs. 22.4 ng/mL, p-value=0.029). Serum 25(OH)D concentrations were significantly inversely correlated with PASI scores at the 6-month follow-up. No major adverse event was observed overall. Conclusion Oral vitamin D2 supplementation in patients with psoriasis increased the serum vitamin D level and significantly improved the treatment outcome without increasing adverse events. Trial Registration This trial is registered with Thai Clinical Trials Registry TCTR20180613001.

Vitamin D3 is known to be liposoluble and its release could be a factor limiting the rate of absorption. It was presumed that the presence of fat could favor absorption of vitamin D3. However, as bioavailability is related not only to the active molecules but also to the formulations and excipients used, the optimization of the pharmaceutical form of vitamin D3 is also important. The objective of this study was to evaluate if there is a food effect on absorption when a high dose of vitamin D3 is completely solubilized in an oily solution. In the present cross-over study, 88 subjects were randomized and received a single dose of 50,000 IU of vitamin D3 in fasting state or with a standardized high-fat breakfast. Assessment of serum concentrations of 25 hydroxyvitamin D3 (25(OH)D3) was performed three, five, seven, 14, 30 and 60 days after supplementation. In fed and fast conditions, the 25(OH)D3 serum concentrations were significantly higher than the baseline value three days after administration and remained significantly higher during the first month. No significant difference between fasting vs. fed conditions was observed. It is therefore concluded that the vitamin D3 absorption from an oily solution was not influenced by the presence or absence of a meal.

To study the adequate intake (AI) for vitamin D in the elderly, we have performed an intervention study with 800 IU/d of vitamin D(3) in the institutionalized elderly. Sixty-two institutionalized elderly were randomly assigned to two groups; receiving either supplements of 200 mg calcium plus 800 IU vitamin D(3)/d (Ca+VD group), or supplements of 200 mg calcium/d (Ca group) for 30 d in October. Serum concentrations of 25-hydroxyvitamin D (25OH-D), parathyroid hormone (PTH), and bone turnover markers were measured before and after intervention. Average dietary vitamin D intake during the intervention period was approximately 300 IU/d in both groups, exceeding the AI in Dietary Reference Intakes for Japanese 2005 of 200 IU/d. In both groups, mean serum 25OH-D level at baseline fell into the hypovitaminosis D range (9.7 ng/mL), despite apparently adequate vitamin D intake. Serum PTH level at baseline was within the reference range. Mean serum 25OH-D concentration significantly increased to 19.3 ng/mL in the Ca+VD group and to 11.1 ng/mL in the Ca group. Post intervention serum 25OH-D level was significantly higher in the Ca+VD group than in the Ca group (p<0.001). In 53 subjects (85.5%) who took more than 80% of their supplements for 30 d, serum PTH level in the Ca+VD group was significantly lower than in the Ca groups (p=0.05). Bone turnover markers were not significantly changed after intervention in either group. Daily supplementation of 800 IU vitamin D(3) was considered effective in the institutionalized elderly with minimal chance of sun exposure, but further studies with longer duration are necessary.

The current study was conducted to assess the effects of simultaneous usage with vitamin D3 and chromium picolinate (CrPic) supplementations on homeostasis model assessment of insulin resistance (HOMA-IR), fasting blood glucose (FBS), hemoglobin A1c (HbA1c), tumor necrosis factor-α (TNF-α), and lipid profile in type 2 diabetes mellitus (T2DM). Ninety-two patients with T2DM were randomly allocated to the following 4 groups for 4 months: (I) placebo of vitamin D3 (n = 23); (II) vitamin D3 supplement at a dose of 50 000 IU/week (n = 23); (III) CrPic supplement at a dose of 500 μg/day (n = 23); and (IV) both vitamin D3 at a dose of 50 000 IU/week and CrPic at a dose of 500 μg/day (n = 23). HOMA-IR levels increased significantly in groups I and II after the intervention. However, this increase in group I was significantly higher than that in group II after the treatment. HOMA-IR levels were controlled in groups III and IV during the intervention. TNF-α decreased significantly in groups II, III, and IV after the intervention. FBS, HbA1c, and lipid profile did not change significantly in total groups after the intervention. It seems that chromium and vitamin D3 co-supplementation are probably effective in controlling HOMA-IR by decreasing TNF-α in T2DM. Novelty Chromium alone and/or in simultaneous pretreatment with vitamin D3 is more effective than vitamin D3 in controlling HOMA-IR in T2DM. Chromium and vitamin D3 alone and/or in simultaneous pretreatment decrease TNF-α in T2DM.

The immunomodulatory role of vitamin D3 in autoimmune diseases is widely hypothesized, but its therapeutic efficacy remains contested. This meta-analysis quantifies the effect of vitamin D3 supplementation on biochemical, endocrine, and inflammatory parameters across various autoimmune conditions. We systematically searched five databases for randomized controlled trials (RCTs) comparing vitamin D3 to placebo/control in autoimmune disease patients. Data from 27 RCTs (n = 1864) were pooled using a random-effects model. Subgroup analyses were conducted based on disease type, dosage, and duration. Vitamin D3 supplementation significantly increased serum 25(OH)D levels (WMD: 53.01 nmol/L, 95% CI: 36.29-69.73, p < 0.001). It induced modest but significant increases in serum calcium (WMD: 0.18 mmol/L) and reductions in parathyroid hormone (WMD: - 8.37 pg/mL) and the inflammatory markers CRP (WMD: - 2.33 mg/L) and IL-6 (WMD: - 0.76 pg/mL). Benefits were more pronounced with longer duration (≥ 6 months) and in patients with multiple sclerosis. However, vitamin D3 showed no significant effect on key disease-specific outcomes, including neurofilament light chain in MS, hemoglobin A1c in type 1 diabetes, or pain scores in rheumatoid arthritis. Vitamin D3 effectively corrects deficiency and exerts modest, systemic anti-inflammatory effects in autoimmune patients. Its impact is context-dependent, influenced by treatment duration and specific disease, supporting its role as a safe adjunctive therapy, though its effect on core disease activity markers is limited. There was significant heterogeneity (I2 > 90% for the majority of outcomes), which reflects actual clinical and methodological variation between trials. Although there is still some unexplained heterogeneity, subgroup analysis by disease type, duration, and dosage identified significant effect modifiers. Therefore, rather than being exact predictions for specific individuals, pooled estimates should be understood as average effects across various populations.

There has been increasing interest in recent years in the prevalence of low 25-hydroxy (OH) vitamin D concentrations in different human populations There are 2 forms of vitamin D: cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2). Vitamin D3 is manufactured through the photoisomerization of 7-dehydrocholesterol to pre-vitamin D3, which then undergoes a temperature-dependent rearrangement to form vitamin D3. Vitamin D2 is a plant sterol found in foods, such as fatty fish, codliver oil, and eggs. Vitamin D is converted to 25-OH vitamin D, the major circulating form of vitamin D, and then to 1, 25-diOH vitamin D, the active form of vitamin D, by enzymes in the liver and kidney. 25-OH vitamin D assays should be able to measure both the D2 and D3 forms of 25-OH vitamin D as both forms are biologically active after 1--hydroxylation. For the majority of patients, total 25-OH vitamin D measurement is suitable for the diagnosis and monitoring of vitamin D deficiency. Quantification of 25-OH vitamin D2 and 25-OH vitamin D3 fractions may be useful in monitoring patients without clinical improvement despite treatment where inadequate dosing, non-adherence, or malabsorption are suspected