Value of Vitamin D Metabolite Ratios in 3 Patients as Diagnostic Criteria to Assess Vitamin D Status.

Although clinical guidelines recommend measuring total plasma 25-hydroxyvitamin D (25[OH]D) to assess vitamin D (VitD) status, this index does not account for 3-fold inter-individual variation in VitD binding protein (VDBP) level. We present 3 individuals with total plasma 25(OH)D levels of 10.8 to 12.3 ng/mL (27-30.7 nmol/L). Because Endocrine Society guidelines define VitD deficiency as 25(OH)D ≤ 20 ng/mL (50 nmol/L), all 3 would be judged to be VitD deficient. VitD3 supplementation increased 25(OH)D to the range of 31.7 to 33.8 ng/mL (79.1-84.4 nmol/L). Patient #1 exhibited secondary hyperparathyroidism; VitD3 supplementation decreased parathyroid hormone (PTH) by 34% without a clinically significant change in PTH levels in the other 2 individuals. Thus, 25(OH)D level did not distinguish between the 1 patient who had secondary hyperparathyroidism and the 2 who did not. We therefore inquired whether VitD metabolite ratios (which are VDBP-independent) might distinguish among these 3 individuals. Of all the assessed ratios, the 1,25(OH)2D/24,25(OH)2D ratio was the most informative, which had a value of 102 pg/ng in the individual with secondary hyperparathyroidism but lower values (41 and 20 pg/ng) in the other 2 individuals. These cases illustrate the value of the 1,25(OH)2D/24,25(OH)2D ratio to provide clinically relevant information about VitD status.

Role of vitamin D supplement adjunct to topical benzoyl peroxide in acne: a randomized double-blinded controlled study.

Background: Acne is an inflammatory condition of the pilosebaceous unit. Previous studies have established a link between acne and vitamin D deficiency and the potential effectiveness of vitamin D supplementation in treatment. However, the efficacy of vitamin D as an adjuvant treatment for acne remains unknown. Objective: To evaluate the efficacy of weekly vitamin D2 oral administration as an adjunctive treatment to standard topical care for acne. Methods: This study was a randomized, double-blind, placebo-controlled trial including subjects with mild-to-moderate acne. Topical 2.5% benzoyl peroxide was applied twice daily for 12 weeks to all subjects. Subjects were randomly allocated to receive either oral vitamin D2 40,000 IU weekly or placebo weekly during the treatment period. No additional treatment was administered during the 4-week follow-up period. Results: A total of 44 subjects were included in this study. All of them had inadequate 25(OH)D levels. Both regimens showed significant improvement in acne during the treatment period. Weekly vitamin D2 supplementation significantly prevented the relapse of inflammatory acne lesions (P = .048) at the follow-up visit. No adverse effects or biochemical changes were observed. Limitations: There were no subjects of severe acne vulgaris. Conclusion: Adjunctive weekly vitamin D2 supplementation to standard topical benzoyl peroxide could reduce relapses of inflammatory lesions in mild-to-moderate acne.

Associations of vitamin D status with all-cause and cause-specific mortality in long-term prescription opioid users.

Objective: This study aimed to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) concentrations and mortality in long-term prescription opioid users. Methods: The study included 1856 long-term prescription opioid users from the National Health and Nutrition Examination Survey (NHANES, 2001-2018). Mortality status were determined by matching with the National Death Index (NDI) records until December 31, 2019. Multivariable Cox proportional hazard models were constructed to assess the association. Results: Over a median follow-up period of 7.75 years, there were 443 cases of all-cause mortality, including 135 cardiovascular disease (CVD) deaths and 94 cancer deaths. After multivariable adjustment, participants with serum 25(OH)D concentrations within 50.00 to <75.00 nmol/L and ≥ 75 nmol/L had a lower risk of all-cause mortality, with hazard ratios (HRs) of 0.50 (95% confidence interval [CI] 0.29, 0.86) and 0.54 (95% CI 0.32, 0.90), respectively. Nevertheless, no significant association was found between serum 25(OH)D concentrations and the risk of CVD or cancer mortality. The RCS analysis revealed a non-linear association of serum 25(OH)D concentration with all-cause mortality (p for non-linear = 0.01). Per 1-unit increment in those with serum 25(OH)D concentrations <62.17 nmol/L corresponded to a 2% reduction in the risk of all-cause mortality (95% CI 0.97, 1.00), but not changed significantly when 25(OH)D concentrations ≥62.17 nmol/L. Conclusion: In conclusion, a non-linear association existed between serum 25(OH)D concentrations and all-cause mortality in long-term prescription opioid users. Maintaining serum 25(OH)D concentrations ≥62.17 nmol/L may be beneficial in preventing all-cause mortality in this population.

Association of a dietary pattern related to serum vitamin D levels with metabolic syndrome risk among Korean adults: based on the Korean national health and nutrition examination survey.

PURPOSE: Vitamin D has a crucial role in our metabolic health. We aimed to examine associations of vitamin D status and its related dietary pattern (DP) with prevalent risk of metabolic syndrome (MetS) in 9,237 Korean adults aged 19-64 years based on the National Health and Nutrition Examination Survey. METHODS: Vitamin D status was examined by serum 25-hydroxyvitamin D (25(OH)D). A vitamin D-related DP associated with 25(OH)D levels was derived using reduced rank regression (RRR). Associations of vitamin D status and its related DP with MetS prevalence were examined using multivariable logistic regression models adjusted for potential confounders. RESULTS: Men with sufficient vitamin D status had a 44% lower risk of MetS prevalence (OR: 0.56; 95%CI: 0.36-0.87) compared to those with deficiency. A vitamin D-related DP derived using RRR was characterized by high intakes of vegetables, fish, fruits, and nuts and low intakes of eggs, oils, and mushrooms in this study population. Among men, the DP was significantly associated with a lower risk of MetS prevalence, showing a 12% (95%CI: 4-20%) reduction in risk for a one-unit increase in the DP score. However, there was no significant association among women. CONCLUSION: The study's findings suggest that a sufficient vitamin D status and a related DP with high intakes of vegetables, fish, fruit, and nuts were associated with the risk of MetS, particularly in Korean male adults.

Assessment of Vitamin D Status in Primary Hyperparathyroidism Patients: A Retrospective Study.

BACKGROUND: Primary hyperparathyroidism (PHPT), a condition that manifests in various clinical forms, is a significant health concern. Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by normal calcemia despite elevated parathyroid hormone (PTH) levels. Vitamin D deficiency can contribute to the clinical spectrum and complexity of NPHPT. Low vitamin D levels can elevate PTH, making it difficult to distinguish between NPHPT and secondary hyperparathyroidism. Additionally, it might mask hypercalcemia, leading to an underestimation of the disease severity. Our study aims to shed light on these complexities by investigating normocalcemic and hypercalcemic PHPT patient's clinical, hormonal, and biochemical patterns, including their vitamin D status.    Materials: In this retrospective study, we enrolled 60 PHPT patients with autonomous parathyroid function confirmed using a combination of ultrasonography, radionuclide scan, and parathyroid function index calculation. We evaluated the albumin-corrected calcemia, calciuria, PTH, 25(OH)D level, serum phosphate, bone mineral density, and major clinical symptoms (fracture, nephrolithiasis). A comparative analysis and a correlation study were performed between normo- and hypercalcemic and vitamin D-deficient and vitamin D-non-deficient groups. RESULTS:  The median age was 62 years, 51.66% (31/60) being normocalcemic and 46.66% (29/60) presenting a deficient 25(OH)D level. In the group with 25(OH)D below 20 ng/mL, we observed a reduced level of albumin-corrected calcemia, without a significant increase of PTH compared to the adequate 25(OH)D level group. The frequency of the NPHPT and the risk of fracture were significantly higher in the deficient 25(OH)D group (20/60, 33.33% and 8/60, 13.33%) than in the adequate one (11/60, 18.33% and 1/60, 1.66%) with OR=4.7 (p<0.004) and OR=9.7 (p<0.027), respectively. We also found a positive correlation between PTH and adenoma size, the parathyroid function index and adenoma size, as well as PTH and phosphate levels. However, the correlation between 25(OH)D and phosphate levels was negative and moderate (rho=-0.504, p<0.001), adding a new layer of complexity to our understanding of these relationships. CONCLUSION: Our study provided significant insight into the link between vitamin D status and normocalcemic PHPT. We found that vitamin D-deficient patients with normocalcemic PHPT have an increased fracture risk, which requires meticulous monitoring and possible supplementation with vitamin D. This should be done carefully to avoid exacerbating hypercalcemia or hypercalciuria. Further research is needed to refine these management strategies and deepen our understanding of the complex relationships between the analyzed parameters.

The Impact of Vitamin D Deficiency on Gestational Diabetes Mellitus Risk: A Retrospective Study.

Background Nowadays, there has been growing attention to vitamin D deficiency's impact on women of reproductive age, both during pregnancy and the preconception period. Because of its possible impact on female reproductive ability, vitamin D deficiency may have multiple implications for maternal and fetal health. Currently, the correlation between vitamin D deficiency and gestational diabetes mellitus (GDM) is gaining attention, mainly due to contradictory findings in the literature. Methods We conducted a single-center, retrospective study involving data from 106 pregnant women to establish a possible link between vitamin D deficiency and GDM risk. We analyzed variables such as vitamin D status, the occurrence of gestational diabetes, and body mass index to identify significant statistical correlations among them. Results Within our study group, the average vitamin D level was 19.5 ± 7.8 ng/mL. Regarding vitamin D status, 59 (55.7%) pregnant women had vitamin D deficiency, 36 (34%) had vitamin D insufficiency, and 11 (10.4%) had optimal vitamin D levels. GDM was diagnosed in 18 cases, representing 17%. After the statistical analysis, we found a positive correlation between gestational diabetes and vitamin D deficiency (chi-square = 4.472, p = 0.049). However, we did not find a significant correlation between gestational diabetes and optimal vitamin D status. Conclusions Pregnant women with vitamin D deficiency are at an increased risk of developing GDM and may benefit from vitamin D supplementation. We believe that further research is necessary to have a comprehensive understanding of vitamin D's effects on pregnancy.

Relationship between non-alcoholic fatty liver and progressive fibrosis and serum 25-hydroxy vitamin D in patients with type 2 diabetes mellitus.

OBJECTIVE: We aimed to analyze the relationship between non-alcoholic fatty liver and progressive fibrosis and serum 25-hydroxy vitamin D (25(OH)D) in patients with type 2 diabetes mellitus. METHODS: A total of 184 patients with T2DM who were hospitalized in the Department of Endocrinology of the ShiDong Clinical Hospital between January 2023 and June 2023 were selected. We compared review of anthropometric, biochemical, and inflammatory parameters and non-invasive scores between groups defined by ultrasound NAFLD severity grades.We determine the correlation between 25(OH)D and FLI and FIB-4 scores, respectively. RESULTS: Statistically significant differences were seen between BMI, WC, C-peptide levels, FPG, ALT, serum 25(OH)D, TC, HDL, lumbar spine bone density, FLI, and FIB-4 in different degrees of NAFLD. Multivariate logistic regression analysis showed that 25(OH)D (OR = 1.26, p = 0.001), age (OR = 0.93, P < 0.001) and BMI (OR = 1.04, p = 0.007) were independent predictors of NAFLD in patients with T2DM. CONCLUSIONS: This study revealed the correlation between serum 25(OH)D levels and NAFLD in patients with T2DM. We also demonstrated that serum 25(OH)D levels were negatively correlated with FLI/FIB-4 levels in patients with T2DM with NAFLD, suggesting that vitamin D deficiency may promote hepatic fibrosis progression in T2DM with NAFLD.

Blood 25-hydroxyvitamin D3 concentration of Japanese Black cattle at two farms with different rearing environments, Kagoshima prefecture, Japan.

Forty-two Japanese Black cattle on two farms in Kagoshima prefecture, Japan were used in this study. The rearing style of farm A was in a dark barn with a large roof to block sunlight (n=21). The rearing style of farm B was grazing, and exposed to direct sunlight (n=21). Blood sampling was performed twice on the same cattle in August 2022 (summer) and February 2023 (winter). As the results, the serum 25(OH)D3 concentrations were significantly lower in cattle of farm A than in cattle of farm B (P<0.01), and were significantly lower in winter season than in summer season (P<0.01). These results showed that there were differences in blood 25(OH)D3 concentrations between the farms or seasons.

Potential causal association between serum vitamin D levels and intervertebral disc degeneration: A mendelian randomization study.

OBJECTIVES: Intervertebral disc degeneration (IDD) is a prevalent musculoskeletal disorder with substantial implications for disability and healthcare expenditures. The role of serum vitamin D (25-Hydroxyvitamin D, 25(OH)D) levels in the pathogenesis of various musculoskeletal conditions has been explored in prior observational studies, suggesting a potential association. While previous observational studies have suggested an association between the two conditions, it might confound the effect of 25(OH)D on IDD. This Mendelian randomization (MR) study seeks to elucidate the causal relationship between 25(OH)D and IDD. METHODS: We performed a MR analysis using summary-level data from genome-wide association studies (GWAS) of 25(OH)D (sample size = 441,291 European) and IDD (sample size = 336,439 (cases = 41,669, controls = 294,770) European). Single nucleotide polymorphisms (SNPs) significantly associated with 25(OH)D (p < 5 × 10-8) were selected as instrumental variables. The associations between genetically predicted 25(OH)D and IDD were estimated using the inverse-variance weighted (IVW) method, with sensitivity analyses employing the weighted median, MR-Egger, and MR-PRESSO approaches to assess the robustness of the findings. RESULTS: In the primary IVW analysis, genetically predicted 25(OH)D was unrelated associated with IDD (odds ratio (OR) = 0.9671, 95% confidence interval (CI): 0.8956-1.0444, p = 0.39). The results remained consistent across the sensitivity analyses, and no significant directional pleiotropy was detected (MR-Egger intercept: p = 0.64). CONCLUSIONS: This study found no obvious evidence that 25(OH)D is causally associated with IDD risks. We call for larger sample size studies to further unravel the potential causal relationship and the exact mechanism.

Vitamin D status in female dogs with mammary gland tumors.

BACKGROUND: Little information exists about vitamin D status in bitches with mammary tumors. OBJECTIVES: To determine whether low plasma vitamin D concentrations are found in bitches with mammary tumors. ANIMALS: Eighty-five client-owned bitches with mammary tumors (n = 21 benign, n = 64 malignant) and 39 age-matched healthy bitches. METHODS: Case-control study. Plasma ionized and total calcium, phosphorus, magnesium, urea, creatinine, albumin, total proteins, alanine aminotransferase, alkaline phosphatase, parathyroid hormone (PTH), calcitriol (1,25-dihydroxyvitamin D), and 25-hydroxyvitamin D concentrations were measured in all bitches at the time of clinical diagnosis and before any treatments. Statistical analysis was performed to compare variables among groups (control, benign, and malignant). RESULTS: No significant differences were found when plasma 25-hydroxyvitamin D concentrations in bitches with malignant (148.9 [59.9] ng/mL) and benign mammary tumors (150.1 [122.3] ng/mL) were compared with control group (129.9 [54.5] ng/mL). Parathyroid hormone was significantly higher in bitches with malignant (19.9 [20.5] pg/mL), and benign mammary tumors (14.6 [14.9] pg/mL) compared with control group (7.5 [7.5] pg/mL; P < .01). Only the presence of mammary tumors (P < .01) and age (P = .04; adjusted R2 = .22) was significant in predicting PTH. CONCLUSIONS: Bitches with mammary tumors do not have low 25-hydroxyvitamin D concentrations thus vitamin D supplementation is unlikely to be useful for prevention of mammary tumors in bitches.

Association of selected adipokines with vitamin D deficiency in children with inflammatory bowel disease.

BACKGROUND: Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency. METHODS: The study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants. RESULTS: Children with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines. CONCLUSIONS: Whether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency.

[Relationship between serum 25-hydroxyvitamin D and handgrip strength in middle-aged and elderly people in five cities of Western China].

OBJECTIVE: To explore the association between serum 25-hydroxyvitamin D [25(OH)D] and handgrip strength in middle-aged and elderly people in 5 cities of Western China. METHODS: Based on the data of a cross-sectional survey conducted in the 5 cities of Western China from February to July 2023, the relevant demographic characteristics of people were collected by questionnaire, handgrip strength was collected by physical examination, and serum 25(OH)D was detected by HPLC-MS/MS. The association between the serum 25(OH)D and handgrip strength was analyzed using Logistic regression and Chi-square test for between-group comparisons models. RESULTS: The prevalence of 25(OH)D deficiency and insufficiency among the middle-aged and elderly people in the 5 cities of Western China was 52.9% and 34.5%, respectively. The people who were older, female, and sampled in winter had lower serum 25(OH)D levels (P < 0.05). The prevalence of loss of handgrip strength among the middle-aged and elderly people was 25.3%. The prevalence of handgrip strength loss was higher in the aged 65-80 participants with 25(OH)D deficiency (45. 0%) than in those with 25(OH)D insufficiency (32.6%) and 25(OH)D sufficiency (20.6%). The highest prevalence of loss of handgrip strength was found in the aged 75-80 participants with 25(OH)D deficiency (62. 1%), followed by the 25(OH)D insufficient group (11.1%, P < 0.05). The study found that middle-aged and elderly people with 25(OH)D deficiency had a 1.4-fold increased risk of handgrip strength loss compared with those with 25(OH)D sufficiency (OR=2.403, 95%CI: 1.202-4.804, P=0.013). No significant association was found between 25(OH)D insufficiency and handgrip strength status in the middle-aged and elderly people. For every 5 µg/L increase in total serum 25(OH)D, the risk of handgrip strength loss reduced by 13.1% (OR=0.869, 95%CI: 0.768-0.982, P=0.025). For every 5 µg/L increase in serum 25(OH)D2, the risk of handgrip strength loss reduced by 24.1% (OR=0.759, 95%CI: 0.582-0.990, P=0.042). No significant association was found between serum 25(OH)D3 levels and the risk of handgrip strength loss. The risk of handgrip strength loss in middle-aged and elderly people was reduced by 25.2% for each incremental increase in the total serum 25(OH)D levels (deficient, insufficient and sufficient) (OR=0.748, 95%CI: 0.598-0.936, P=0.011). The risk of handgrip loss was reduced by 40.0% for each incremental increase in serum 25(OH)D levels in the aged 65-80 and aged 65-69 participants, and by 80.0% for each incremental increase in 25(OH)D levels in the aged 75-80 parti-cipants. CONCLUSION: Serum total 25(OH)D and 25(OH)D2 levels are associated with handgrip strength status in middle-aged and elderly people in the 5 cities of Western China.

Serum 25-Hydroxyvitamin D Level Is Positively Associated with Vascular Reactivity Index in Patients with Type 2 Diabetes Mellitus.

Circulating 25-hydroxyvitamin D (25(OH)D) significantly influences endothelial function. This study assessed the correlation between serum 25(OH)D and endothelial function using the vascular reactivity index (VRI) in patients with type 2 diabetes mellitus (T2DM). Fasting blood samples from 102 T2DM participants and VRI were assessed. Patients were divided into three categories based on VRI: low (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), and good (VRI ≥ 2.0). Among these patients, 30 (29.4%) had poor, 39 (38.2%) had intermediate, and 33 (32.4%) exhibited good vascular reactivity. Higher serum fasting glucose (p = 0.019), glycated hemoglobin (p = 0.009), and urinary albumin-to-creatinine ratio (p = 0.006) were associated, while lower prevalence of hypertension (p = 0.029), lower systolic blood pressure (p = 0.027), lower diastolic blood pressure (p < 0.001), and lower circulation 25(OH)D levels (p < 0.001) were associated with poor vascular reactivity. Significant independent associations between diastolic blood pressure (p = 0.002) and serum 25(OH)D level (p < 0.001) and VRI were seen in T2DM patients according to multivariable forward stepwise linear regression analysis. Serum 25(OH)D positively correlated with VRI values, and lower levels of serum 25(OH)D were linked to endothelial dysfunction in T2DM patients.

Serum 25-hydroxyvitamin D level and erectile dysfunction: a causal relationship? Findings from a two-sample Mendelian randomization study.

Background: Serum 25-hydroxyvitamin D level is associated with erectile dysfunction (ED) in observational studies. However, whether there is a causal association between them remains uncertain. Objective: Conduct a two-sample Mendelian randomization (MR) analysis to investigate the causal effect between serum 25-hydroxyvitamin D level and ED risk. Method: Genome-wide association study (GWAS) data of serum 25-hydroxyvitamin D levels comprising 6,896,093 single nucleotide polymorphisms (SNP) from 496,949 people of European ancestry were regarded as exposure for the MR analysis. Additional GWAS data involving 9,310,196 SNPs of 6,175 European ED cases and 217,630 controls were used as outcome data. The MR-Egger, inverse variance weighted (IVW) method, weighted median, simple mode, and weighted mode were employed to evaluate causal effects, among which IVW was the primary MR analysis method. The stability of the MR analysis results was confirmed by a heterogeneity test, a horizontal pleiotropy test, and the leave-one-out method. Result: There were 103 SNPs utilized as instrumental variables (p < 5 × 10-8). The results of MR analysis showed no causal effects of serum 25(OH) D concentration on ED risks (IVW; OR = 0.9516, 95% CI = 0.7994 to 1.1328, p = 0.5772). There was no heterogeneity and pleiotropy in the statistical models. Conclusion: The present MR study did not support a causal association for genetically predicted serum 25-hydroxyvitamin D concentration in the risk of ED in individuals of European descent.

A Cross-Sectional Exploratory Study of Cardiovascular Risk Biomarkers in Non-Obese Women with and without Polycystic Ovary Syndrome: Association with Vitamin D.

Vitamin D is proposed to have a protective effect against cardiovascular disease, though the mechanism is unclear. Vitamin D deficiency is common in polycystic ovary syndrome (PCOS), where it is strongly related to obesity, insulin resistance (IR) and risk of cardiovascular disease. To determine if the inherent pathophysiology of PCOS or vitamin D levels are linked to dysregulation of cardiovascular risk proteins (CVRPs), a study in non-obese women with PCOS and without IR was undertaken. Our hypothesis was that the levels of vitamin D3 and its active metabolite would be associated with CVRPs comparably in women with and without PCOS. In women with PCOS (n = 29) and controls (n = 29), 54 CVRPs were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement and correlated to 25-hydroxyvitamin D3 (25(OH)D3) and the active 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) measured by gold standard isotope-dilution liquid chromatography tandem mass spectrometry. Women with PCOS had comparable IR and systemic inflammation (normal C-reactive protein) to control women, though had higher free androgen index and anti-Mullerian hormone levels. 25(OH)D3 and 1,25(OH)2D3 levels did not differ between groups. Nine CVRPs were higher in PCOS (p < 0.05) (Galectin-9, Brother of CDO, C-motif chemokine 3, Interleukin-18 receptor-1, Thrombopoietin, Interleukin-1 receptor antagonist protein, Programmed cell death 1 ligand-2, Low-affinity immunoglobulin gamma Fc-region receptor II-b and human growth hormone), whilst 45 CVRPs did not differ. 25(OH)D3 correlated with five CVRPs in PCOS and one in controls (p < 0.05). Despite the women with PCOS not exhibiting overt systemic inflammation, 9 of 54 CVRPs were elevated, all relating to inflammation, and 5 of these correlated with 25(OH)D3, suggesting an ongoing underlying inflammatory process in PCOS even in the absence of obesity/IR.

Causal association between 25-hydroxyvitamin D status and cataract development: A two-sample Mendelian randomization study.

BACKGROUND: Vitamin deficiencies are linked to various eye diseases, and the influence of vitamin D on cataract formation has been noted in prior research. However, detailed investigations into the causal relationship between 25-(OH)D status and cataract development remain scarce. AIM: To explore a possible causal link between cataracts and vitamin D. METHODS: In this study, we explored the causal link between 25-(OH)D levels and cataract development using Mendelian randomization. Our analytical approach included inverse-variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. The primary analyses utilized IVW with random effects, supplemented by sensitivity and heterogeneity tests using both IVW and MR-Egger. MR-Egger was also applied for pleiotropy testing. Additionally, a leave-one-out analysis helped identify potentially impactful single-nucleotide polymorphisms. RESULTS: The analysis revealed a positive association between 25-(OH)D levels and the risk of developing cataracts (OR = 1.11, 95%CI: 1.00-1.22; P = 0.032). The heterogeneity test revealed that our IVW analysis exhibited minimal heterogeneity (P > 0.05), and the pleiotropy test findings confirmed the absence of pleiotropy within our IVW analysis (P > 0.05). Furthermore, a search of the human genotype-phenotype association database failed to identify any potentially relevant risk-factor single nucleotide polymorphisms. CONCLUSION: There is a potential causal link between 25-(OH)D levels and the development of cataracts, suggesting that greater 25-(OH)D levels may be a contributing risk factor for cataract formation. Further experimental research is required to confirm these findings.

Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline.

BACKGROUND: Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain. OBJECTIVE: To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing. METHODS: A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined "empiric supplementation" as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D. RESULTS: The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D-containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity. CONCLUSION: The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.

Vitamin D Insufficiency and Epistemic Humility: An Endocrine Society Guideline Communication.

A long-held precept is that vitamin D supplementation primarily, if not exclusively, benefits individuals with low circulating 25-hydroxyvitamin D (25[OH]D) concentrations at baseline. However, the most appropriate 25(OH)D threshold to distinguish unacceptably low vs reliably adequate concentrations remains controversial. Such threshold proposals have largely been based on observational studies, which provide less robust evidence compared to randomized clinical trials (RCTs). Since the Endocrine Society's first vitamin D-related guideline was published in 2011, several large vitamin D-related RCTs have been published, and a newly commissioned guideline development panel (GDP) prioritized 4 clinical questions related to the benefits and harms of vitamin D supplementation in generally healthy individuals with 25(OH)D levels below a threshold. The GDP determined that available clinical trial evidence does not permit the establishment of 25(OH)D thresholds that specifically predict meaningful benefit with vitamin D supplementation. The panel noted important limitations in the available evidence, and the panel's overall certainty in the available evidence was very low. Nonetheless, based on the GDP's analyses and judgments, the Endocrine Society no longer endorses its previously proposed definition of vitamin D "sufficiency" (ie, at least 30 ng/mL [75 nmol/L]) or its previously proposed definition of vitamin D "insufficiency" (ie, greater than 20 ng/mL [50 nmol/L] but lower than 30 ng/mL [75 nmol/L]). The Endocrine Society's rationale for such is the subject of this Guideline Communication.

Concurrent nutrient deficiencies are associated with dementia incidence.

INTRODUCTION: While observational research suggests a protective role for nutrition in brain aging, intervention studies remain inconclusive. This failing translation from observational to interventional research may result from overlooking nutrient interactions. METHODS: We developed a nutrient status index capturing the number of suboptimal statuses of omega-3 fatty acids, homocysteine, and vitamin D (range 0 to 3). We associated this index with dementia incidence in a subsample (age ≥ 50 years) of the Framingham Heart Study Offspring cohort. RESULTS: Among 968 participants, 79 developed dementia over 15.5 years (median follow-up). Each point increase in nutrient status index was associated with a 50% higher risk of dementia (hazard ratio [HR] = 1.50; 95% confidence interval [CI] = 1.16, 1.96). Participants with three high-risk statuses had a four-fold increased risk of dementia compared to participants without high-risk status (HR = 4.68; 95% CI = 1.69, 12.94). DISCUSSION: Concurrent nutrient deficiencies are associated with the risk of dementia. The potential of optimizing nutritional status to lower dementia risk warrants further study. HIGHLIGHTS: Nutrition and dementia research calls for multiple-nutrient approaches. We studied combined suboptimal statuses of omega-3 polyunsaturated fatty acids, homocysteine, and vitamin D. Suboptimal status of the three nutrients was associated with dementia risk. The risk estimate was larger than for other factors (ie, diabetes, apolipoprotein E Îµ4 carrier). Future studies should assess the effect of improving nutrient status on dementia risk.