Vitamin D Metabolite Ratio in Pregnant Women with Low Blood Vitamin D Concentrations Is Associated with Neonatal Anthropometric Data

Existing evidence on the correlation between maternal vitamin D concentrations and birth outcomes is conflicting. Investigation of these associations requires accurate assessment of vitamin D status, especially in individuals with low 25-hydroxyvitamin D (25(OH)D) concentrations. This study examined the correlations between birth outcomes and the maternal vitamin D metabolite ratio (VMR) 1 (defined as the ratio of 24,25(OH)₂D₃ to 25(OH)D) and VMR2 (defined as the ratio of 3-epi-25(OH)D₃ to 25(OH)D) using data from the Japan Environment and Children’s Study at Chiba Regional Center. A total of 297 mother–neonate pairs were analyzed. Using liquid chromatography–tandem mass spectrometry, we measured 25(OH)D₂, 25(OH)D₃, 24,25(OH)₂D₃, and 3-epi-25(OH)D₃ concentrations in maternal serum samples. These data were analyzed in relation to birth anthropometric data using multivariable linear regression. Of the study participants, 85.2% showed insufficient vitamin D concentrations. VMR1 was strongly correlated with 25(OH)D concentrations, whereas VMR2 showed a weak correlation. Only VMR2 was associated with all anthropometric data. VMR2 in pregnant women with low vitamin D blood concentrations is a useful marker for neonatal anthropometric data and is independent of 25(OH)D. Accurate measurement of vitamin D metabolites could help better understand the effects of vitamin D on birth outcomes.     

Fasting and Exercise Induce Changes in Serum Vitamin D Metabolites in Healthy Men

Background: Vitamin D plays pleiotropic roles in the body and hence, changes in its metabolism and distribution during starvation could play an important role in the adaptive response to famine. We aimed to identify the responses of some vitamin D metabolites to 8 d of fasting and exercise. Methods: A repeated-measures design was implemented, in which 14 male volunteers fasted for 8 d and performed an exercise test before and after fasting. Serum samples were collected on day 1 after night fasting and after 8 d of complete food restriction, before and 1 h and 3 h after exercise. Results: After 8 d of fasting, compared with baseline values, serum 24,25(OH)₂D₃ and 3-epi-25(OH)D₃ levels significantly increased; those of 25(OH)D₃ and 1,25(OH)₂D₃ were unaffected; and those of 25(OH)D₂ decreased. Exercise on the first day of fasting induced an increase in serum 3-epi-25(OH)D₃ levels, while exercise performed after 8 d of fasting induced an increase in 25(OH)D₃, 24,25(OH)₂D₃, 25(OH)D₂, and 3-epi-25(OH)D₃ levels. Conclusion: Increases in 24,25(OH)₂D₃ and 3-epi-25(OH)D₃ levels imply that fasting stimulates vitamin D metabolism. The effects of exercise on serum vitamin D metabolites, which are most pronounced after fasting and in subjects with serum 25(OH)D₃ above 25 ng/mL, support the notion that fasting and exercise augment vitamin D metabolism.     

Ultra-Marathon-Induced Increase in Serum Levels of Vitamin D Metabolites: A Double-Blind Randomized Controlled Trial

Purpose: While an increasing number of studies demonstrate the importance of vitamin D for athletic performance, the effects of any type of exercise on vitamin D metabolism are poorly characterized. We aimed to identify the responses of some vitamin D metabolites to ultra-marathon runs. Methods: A repeated-measures design was implemented, in which 27 amateur runners were assigned into two groups: those who received a single dose of vitamin D₃ (150,000 IU) 24 h before the start of the marathon (n = 13) and those (n = 14) who received a placebo. Blood samples were collected 24 h before, immediately after, and 24 h after the run. Results: In both groups of runners, serum 25(OH)D₃, 24,25(OH)₂D₃, and 3-epi-25(OH)D₃ levels significantly increased by 83%, 63%, and 182% after the ultra-marathon, respectively. The increase was most pronounced in the vitamin D group. Body mass and fat mass significantly decreased after the run in both groups. Conclusions: Ultra-marathon induces the mobilization of vitamin D into the blood. Furthermore, the 24,25(OH)₂D₃ and 3-epi-25(OH)D₃ increases imply that the exercise stimulates vitamin D metabolism.     

Vitamin D Metabolite Profile in Cholecalciferol- or Calcitriol-Supplemented Healthy and Mammary Gland Tumor-Bearing Mice

To analyze if the prometastatic activity of calcitriol (active vitamin D₃ metabolite), which was previously observed in a 4T1 breast cancer model, is also found in other breast cancers, and to assess the impact of various schemes of vitamin D supply, we used 4T1 and E0771 mouse metastatic and 67NR nonmetastatic cells in this study. BALB/c and C57BL/6 healthy and tumor-bearing mice were exposed to a control (1000 IU), low- (100 IU), and high- (5000 IU) vitamin D₃ diets. Additionally, from day 7 of tumor transplantation, the 1000 and 100 IU groups were gavaged with calcitriol (+cal). After 8 weeks of feeding, plasma levels of 25(OH)D₃, 24,25(OH)₂D₃, and 3-epi-25(OH)D₃ were significantly lower in calcitriol-treated and vitamin D-deficient groups than in the control, whereas the levels of all metabolites were increased in the 5000 IU group. The ratio of 25(OH)D₃:24,25(OH)₂D₃ was increased in both calcitriol-treated groups, whereas the ratio of 25(OH)D₃:3-epi-25(OH)D₃ was increased only in the 100 IU group but decreased in the 5000 IU group. In contrast to E0771, 4T1 lung metastasis was accelerated in all vitamin D-supplemented mice, as well as in the deficient group with an increased inflammatory response. 67NR tumor growth was transiently inhibited in the 1000 IU+cal group, but single metastases were observed in the 5000 and 100 IU groups. Based on the results, we conclude that various schemes of vitamin D supply and vitamin D deficiency led to similar metabolite profiles irrespective of the mice strain and tumor burden. However, depending on the type of breast cancer, different effects on tumor growth and metastasis were noticed.     

Megalin and Vitamin D Metabolism—Implications in Non-Renal Tissues and Kidney Disease

Megalin is an endocytic receptor abundantly expressed in proximal tubular epithelial cells and other calciotropic extrarenal cells expressing vitamin D metabolizing enzymes, such as bone and parathyroid cells. The receptor functions in the uptake of the vitamin D-binding protein (DBP) complexed to 25 hydroxyvitamin D₃ (25(OH)D₃), facilitating the intracellular conversion of precursor 25(OH)D₃ to the active 1,25 dihydroxyvitamin D3 (1,25(OH)₂D₃). The significance of renal megalin-mediated reabsorption of 25(OH)D₃ and 1,25(OH)₂D₃ has been well established experimentally, and other studies have demonstrated relevant roles of extrarenal megalin in regulating vitamin D homeostasis in mammary cells, fat, muscle, bone, and mesenchymal stem cells. Parathyroid gland megalin may regulate calcium signaling, suggesting intriguing possibilities for megalin-mediated cross-talk between calcium and vitamin D regulation in the parathyroid; however, parathyroid megalin functionality has not been assessed in the context of vitamin D. Within various models of chronic kidney disease (CKD), megalin expression appears to be downregulated; however, contradictory results have been observed between human and rodent models. This review aims to provide an overview of the current knowledge of megalin function in the context of vitamin D metabolism, with an emphasis on extrarenal megalin, an area that clearly requires further investigation.     

Nordic Walking Rather Than High Intensity Interval Training Reduced Myostatin Concentration More Effectively in Elderly Subjects and the Range of This Drop Was Modified by Metabolites of Vitamin D

The COVID-19 pandemic and subsequent self-isolation exacerbated the problem of insufficient amounts of physical activity and its consequences. At the same time, this revealed the advantage of vitamin D. Thus, there was a need to verify the effects of those forms of training that can be performed independently. In this study, we examined the effects of Nordic walking (NW) and high intensity interval training (HIIT) with regard to the impact of the metabolite vitamin D. We assigned 32 overweight adults (age = 61 ± 12 years) to one of two training groups: NW = 18 and HIIT = 14. Body composition assessment and blood sample collection were conducted before starting the training programs and a day after their completion. NW training induced a significant decrease in myostatin (p = 0.05) concentration; however, the range was dependent on the baseline concentrations of vitamin D metabolites. This drop was accompanied by a significant negative correlation with the decorin concentration. Unexpectedly, NW caused a decrement in both forms of osteocalcin: undercarboxylated (Glu-OC) and carboxylated-type (Gla-OC). The scope of Glu-OC changes was dependent on a baseline concentration of 25(OH)D₂ (r = −0.60, p = 0.01). In contrast, the HIIT protocol did not induce any changes. Overall results revealed that NW diminished the myostatin concentration and that this effect is more pronounced among adults with a sufficient concentration of vitamin D metabolites.     

Relative Efficacy of Vitamin D2 and Vitamin D3 in Improving Vitamin D Status: Systematic Review and Meta-Analysis

Background: Widespread prevalence of vitamin D deficiency has been documented globally. Commonly used interventions to address this deficiency include supplementation and/or fortification with either ergocalciferol (vitamin D₂) or cholecalciferol (vitamin D₃), but the relative efficacy of these two vitamers is unclear. The current study aimed to evaluate the relative efficacy of ergocalciferol (vitamin D₂) and cholecalciferol (vitamin D₃) for raising the serum levels of vitamin D metabolites and functional indicators including serum parathyroid (PTH) levels, isometric muscle strength, hand grip strength and bone mineral density. Methods: Randomized and non-randomized controlled studies evaluating relative efficacy of ergocalciferol and cholecalciferol were systematically reviewed to synthesize quantitative and qualitative evidence as per the recommendations of according to “Preferred Reporting Items for Systematic reviews and Meta-analysis” guidelines. Search terms were constructed on the basis of the “participants”, “intervention”, “control”, “outcome” and “study type” (PICOS) strategy to systematically search the popular electronic databases. Relevant data from studies meeting inclusion and exclusion criteria were extracted and analyzed. Meta-regression, subgroup and sensitivity analyses were performed to investigate the influence of study-level characteristics including intervention dosage, frequency of dosing, interval between the last dose and test for outcome assessment, participant characteristics and analytical methods. Results: Apparently healthy human participants (n = 1277) from 24 studies were included for meta-analysis. The quantitative analysis suggested higher efficacy of cholecalciferol than ergocalciferol in improving total 25(OH)D (mean difference: 15.69, 95%CI: 9.46 to 21.93 nmol/L) and reducing PTH levels, consistently across variable participant demographics, dosage and vehicle of supplementation. Meta-regression suggested smaller differences in the efficacy of cholecalciferol and ergocalciferol at lower doses. Average daily dose was the single significant predictor of effect size, as revealed by multivariate meta-regression analysis. Conclusions: Compared to ergocalciferol, cholecalciferol intervention was more efficacious in improving vitamin D status (serum levels of total 25(OH)D and 25(OH)D₃) and regulating PTH levels, irrespective of the participant demographics, dosage and vehicle of supplementation.     

Bariatric Surgery Induced Changes in Blood Cholesterol Are Modulated by Vitamin D Status

The effect of metabolically active bariatric surgery treatment on lipid metabolism is inconclusive. The authors of this study presume that initial vitamin D status may play a regulating role in influencing the beneficial post-effects of bariatric surgery, especially the lipid profile. The biochemical data obtained from 24 patients who had undergone laparoscopic one-anastomosis gastric bypass (OAGB) at baseline, 3 months before the surgery, at the time of surgery, and 6 months later, demonstrate that vitamin D status influenced the postoperative lipid profile. The baseline established the partition line which divided patients into two groups according to the stated calcidiol initial concentration level of 32 ng/mL. The data shows that OAGB induces a decrease in TG and hsCRP while increasing HDL. Conversely, in patients whose 25(OH)D₃ was below 32 ng/mL TC significantly increased while those above this concentration remained in the normal physiological range. The changes induced by OAGB in TG, glucose, and hsCRP were similar in both groups. Unexpectedly, the surgery did not affect vitamin D metabolites. In conclusion, the results of the study suggest that a higher concentration of serum 25(OH)D₃ may enhance the protective effects of OAGB.     

Differences in the Concentration of Vitamin D Metabolites in Plasma Due to the Low-Carbohydrate-High-Fat Diet and the Eastern European Diet—A Pilot Study

Vitamin D deficiency is a global problem with many health consequences, and it is currently recommended to supplement vitamin D. Change of diet should also be considered to ensure adequate vitamin D in the human body. The aim of this study was to assess the concentration of vitamin D metabolites in two different groups: one group on the low-carbohydrate-high-fat (LCHF) diet and the other group on the Eastern European (EE) diet. In the first stage, 817 participants declaring traditional EE diet or LCHF diet were investigated. Nutrition (self-reported 3-day estimated food record) and basic anthropometric parameters were assessed. After extra screening, 67 participants on the EE diet and 41 on the LCHF diet were qualified for the second stage. Plasma 25-hydroxycholecalciferol (25(OH)D₃) and (25(OH)D₂) concentration was measured by the validated HPLC—MS/MS method. Plasma 25(OH)D₃ concentration was significantly higher in the group on the LCHF diet (34.9 ± 15.9 ng/mL) than in the group on the EE diet (22.6 ± 12.1 ng/mL). No statistical differences were observed in plasma 25(OH)D₂ concentration between the study groups (p > 0.05). Women had a higher plasma 25(OH)D₂ concentration than men regardless of diet type. The LCHF diet had a positive influence on plasma vitamin D concentration. However, long-term use of the LCHF diet remains contentious due to the high risk of cardiovascular disease. This study confirmed that the type of diet influences the concentration of vitamin D metabolites in the plasma.     

Inflammatory Markers in Non-Obese Women with Polycystic Ovary Syndrome Are Not Elevated and Show No Correlation with Vitamin D Metabolites

Introduction. Chronic low-grade inflammation is a characteristic of women with polycystic ovary syndrome (PCOS), although this may be obesity-driven rather than an intrinsic facet of PCOS; furthermore, vitamin D deficiency, another common feature of PCOS, is reported to have an association with increased inflammation. Therefore, circulating inflammatory protein levels and circulating levels of vitamin D may be linked in PCOS, though it is unclear which vitamin D metabolites may be important. Methods. We measured plasma levels of 24 inflammatory proteins and 12 matrix metalloproteinases (proteins modulated by the inflammatory process) by slow off-rate modified aptamer (SOMA)-scan plasma protein measurement in weight and aged-matched non-obese non-insulin resistant PCOS (n = 24) and control (n = 24) women. Inflammatory proteins and matrix metalloproteinases were correlated to 25-hydroxy vitamin D₃ (25(OH)D₃), its epimer 25-hydroxy-3epi-vitamin D (3epi25(OH)D) and the active 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) as measured by gold standard isotope-dilution liquid chromatography tandem mass spectrometry. Results. PCOS women had both an elevated free androgen index and circulating anti-mullerian hormone, though insulin resistance was comparable to controls. C-reactive protein, as a standard circulatory marker of inflammation, was comparable between cohorts. Levels of circulating inflammatory proteins and matrix metalloproteinases were not different between the PCOS and control women, with no correlation of 25(OH)D_3, 1,25(OH)₂D₃ or 3epi25(OH)D with any of the inflammatory proteins. Conclusion. In a non-obese PCOS population matched for age and insulin resistance, circulating inflammatory proteins and matrix metalloproteinases were not elevated and did not correlate with 25(OH)D_3, its epimer 3epi25(OH)D or 1,25(OH)₂D₃ in either control or PCOS women, indicating that the inflammatory response is absent and the vitamin D-metabolite independent in non-obese women with PCOS.     

Vitamin D and Cardiovascular Disease

Vitamin D participates in numerous physiologic and pathologic processes. Most tissues have vitamin D receptors (VDRs), and vitamin D is an important regulator of gene expression. Approximately 1 billion people worldwide have insufficient levels of vitamin D. Deficiency has been associated with many chronic diseases, including cardiovascular disease (CVD), which is the leading cause of death in both men and women. A relationship between vitamin D and CVD is implicated; however studies show conflicting data. Epidemiologic evidence and observational studies demonstrate an association between vitamin D deficiency and CVD; however, this is not substantiated by randomized controlled trials (RCTs). Many questions remain unanswered, but growing evidence supports a beneficial role of vitamin D on cardiovascular health.

Key teaching points:

? Vitamin D influences many cellular functions.

? A global pandemic of vitamin D deficiency exists.

? Epidemiologic data and observational studies suggest that vitamin D deficiency may increase cardiovascular risk.

? RCTs show no significant relationship (however, studies have significant limitations).

? The association between vitamin D status and CVD is uncertain, but low vitamin D levels may be an independent and modifiable CV risk factor.

     

Assessment of Vitamin D Status in Slovenian Premenopausal and Postmenopausal Women,Using Total,Free, and Bioavailable 25-Hydroxyvitamin D (25(OH)D)

The objective of our study was to evaluate vitamin D status and its predictors in Slovenian premenopausal and postmenopausal women. A cross-sectional study was carried out between 1 March 2021 and 31 May 2021. A total of 319 healthy women from the Central Slovenian region aged between 44 and 65 were recruited; 176 were included in the final analysis. The vitamin D status was determined by measuring the total 25-Hydroxycholecalciferol (25(OH)D) concentration, vitamin D binding protein (DBP), and albumin and calculating the bioavailable 25(OH)D and free 25(OH)D. For the calculation of bioavailable and free 25(OH)D, we developed a new online calculator. The Endocrine Society’s thresholds for vitamin D deficiency and insufficiency were used; 29.0% of premenopausal and 24.4% of postmenopausal subjects were found to be vitamin D deficient (total 25(OH)D < 50 nmol/L); 76.8% of the premenopausal and 61.7% of postmenopausal subjects were found to have insufficient levels (total 25(OH)D < 75 nmol/L). Premenopausal women had 11.8% lower total 25(OH)D, 32.2% lower bioavailable 25(OH)D, and 25.2% higher DBP than postmenopausal women. The most important predictors of vitamin D status were vitamin D supplementation and time spent in the sun. Contrary to similar studies, the vitamin D status in Slovenian postmenopausal women was significantly better than in premenopausal women. In postmenopausal women, the measurement of free or bioavailable 25(OH)D instead of the total 25(OH)D could be advantageous.     

Vitamin D Deficiency in Pregnant Ukrainian Women: Effects of Alcohol Consumption on Vitamin D Status

Objective: Heavy alcohol consumption can alter vitamin D status; however, the relationships between alcohol consumption and vitamin D concentrations in pregnant women have not been well studied. The aim of this study was to investigate the vitamin D status in a population of alcohol-exposed (N = 180) and low/unexposed control (N = 179) Ukrainian pregnant women.

Methods: Women who attended prenatal care facilities in 2 regions of Ukraine (Rivne and Khmelnytsky) for a routine prenatal visit were screened for the study. At the time of enrollment (20.4 ± 7.0 weeks of gestation), blood samples and alcohol consumption data (during a typical week around conception and the most recent 2 weeks) were collected. Vitamin D status was assessed by 25-hydroxyvitamin D [25(OH)D] concentrations.

Results: A high prevalence of suboptimal vitamin D status in pregnant Ukrainian women was observed. Overall, 50.1% and 33.4% of the women were classified as vitamin D deficient [25(OH)D < 20 ng/mL] or insufficient [25(OH)D ≥ 20 ng/mL and ≤30 ng/mL], respectively, based on 2011 Endocrine Society guidelines. Alcohol-exposed women had significantly lower 25(OH)D concentrations than low/unexposed women in Spring (p = 0.006) and Winter (p = 0.022). When vitamin D concentrations were grouped into sunny season (Summer + Fall) compared to not sunny season (Winter + Spring), there was a significant ethanol by season interaction (p = 0.0028), with alcohol-drinking women having lower circulating vitamin D compared to low/unexposed women in seasons of low sun availability.

Conclusions: These data suggest that when vitamin D concentrations are generally low (e.g., during seasons of low sun availability), alcohol consumption during pregnancy has a negative impact on vitamin D status.     

Association of Dietary Vitamin D Intake,Serum 25(OH)D3, 25(OH)D2 with Cognitive Performance in the Elderly

Background: As life expectancy increases, cognitive performance decline in the elderly has become one of the major global challenges. We aimed to evaluate the association of dietary vitamin D (VD), serum 25-hydroxyvitamin D3 (25(OH)D₃), 25-hydroxyvitamin D2 (25(OH)D₂), and total 25-hydroxyvitamin (25(OH)D) concentration with cognitive performance in older Americans. Methods: The data from the National Health and Nutrition Examination Survey (NHANES), 2011–2014 was used. The cognitive performance was assessed by the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word Learning sub-test, Animal Fluency test, and Digit Symbol Substitution Test (DSST). A binary logistic regression model was applied to evaluate the association between VD and cognitive performance, and restricted cubic spline model was adopted to evaluate the dose–response relationship. Results: While comparing to the lowest dietary VD intake group, the multivariate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of the highest dietary VD intake group were 0.51 (0.36–0.72) for the Animal Fluency test score and 0.45 (0.31–0.66) for DSST score, respectively; and those of serum total 25(OH)D and 25(OH)D₃ concentration were 0.68 (0.47–0.97) and 0.62 (0.44–0.86) for DSST score. L-shaped relationships were identified for dietary VD intake, serum total 25(OH)D and 25(OH)D₃ concentration with cognition performance. The associations between dietary VD intake, serum total 25(OH)D and cognitive performance were non-significant when stratified by gender. Conclusions: The study indicates that dietary VD intake, serum total 25(OH)D and 25(OH)D₃ concentration were positively associated with cognitive performance. Further studies are needed to clarify the possible effects of dietary VD intake and serum 25(OH)D₂, 25(OH)D₃ on cognitive performance.     

Vitamin D Status Is Associated with Modifiable Lifestyle Factors in Pre-Adolescent Children Living in Urban Kuala Lumpur,Malaysia

Studies on vitamin D status and its determinants in growing children in countries with ample sunshine such as Malaysia have been limited. The aim of our study was to determine factors associated with serum 25(OH)D concentrations such as lifestyle, dietary intake, anthropometry, and body composition in 243 pre-adolescent Malaysian children from low-income families living in Kuala Lumpur. This cross-sectional study measured bone density and body composition using dual-energy X-ray absorptiometry (DXA), while serum 25(OH)D was measured using LC–MS/MS. Time spent outdoors, body surface area exposed to sunlight, dietary intake, and physical activity level were assessed using questionnaires. Multiple linear regression and stepwise analysis were performed to identify significant predictors for serum 25(OH)D. About 69.4% had 25(OH)D < 50 nmol/L, and 18.9% were vitamin-D-deficient with 25(OH)D < 30 nmol/L. Girls had a nine-fold higher prevalence of vitamin D deficiency than boys. Body surface area exposed to sunlight, Sun Index, and fat mass were significant predictors of 25(OH)D concentrations in this population. Modifiable lifestyle factors such as sun exposure and reducing obesity are important public health guidance to ensure optimal vitamin D status in these children.     

Factors Affecting 25-Hydroxyvitamin D Concentration in Response to Vitamin D Supplementation

Sun exposure is the main source of vitamin D. Due to many lifestyle risk factors vitamin D deficiency/insufficiency is becoming a worldwide health problem. Low 25(OH)D concentration is associated with adverse musculoskeletal and non-musculoskeletal health outcomes. Vitamin D supplementation is currently the best approach to treat deficiency and to maintain adequacy. In response to a given dose of vitamin D, the effect on 25(OH)D concentration differs between individuals, and it is imperative that factors affecting this response be identified. For this review, a comprehensive literature search was conducted to identify those factors and to explore their significance in relation to circulating 25(OH)D response to vitamin D supplementation. The effect of several demographic/biological factors such as baseline 25(OH)D, aging, body mass index(BMI)/body fat percentage, ethnicity, calcium intake, genetics, oestrogen use, dietary fat content and composition, and some diseases and medications has been addressed. Furthermore, strategies employed by researchers or health care providers (type, dose and duration of vitamin D supplementation) and environment (season) are other contributing factors. With the exception of baseline 25(OH)D, BMI/body fat percentage, dose and type of vitamin D, the relative importance of other factors and the mechanisms by which these factors may affect the response remains to be determined.     

Body Size and Serum 25 Hydroxy Vitamin D Response to Oral Supplements in Healthy Older Adults

Background: Vitamin D insufficiency is prevalent in the northeast United States. Since vitamin D insufficiency is readily amenable to supplementation, it is important to understand what factors are associated with serum 25 hydroxy vitamin D (25(OH)D) response to vitamin D supplementation.

Objective: In this study we examined the association of serum 25(OH)D response to vitamin D supplementation with body size in a population of elderly subjects.

Methods: 257 healthy, ambulatory men and women 65 years of age or older were randomly assigned to treatment with either 700 IU/day (17.5 μg/d) of supplemental vitamin D₃ and 500 mg/day (12.5 mmol/d) of supplemental calcium, or to placebo.

Results: In multivariate regression analyses, after adjusting for baseline 25(OH)D, season, and sex, we found change in 25(OH)D to be inversely associated with baseline BMI (p = 0.01) in subjects treated with supplements for one year. Change in 25(OH)D was also negatively associated with other baseline anthropometric measurements in these subjects.

Conclusion: Our study implies that body size should be taken into account when estimating the amount of vitamin D intake needed to raise 25(OH)D to the desired level.     

Smoking Exposure Is Associated with Serum Vitamin D Deficiency in Children: Evidence from the Japan Environment and Children’s Study

Tobacco smoke exposure is known to lower serum 25-hydroxyvitamin D (25(OH)D) concentrations. This study evaluated the association between passive smoking and vitamin D deficiency (VDD) in young children using data from the Japan Environment and Children’s Study (JECS), the largest birth cohort study in Japan. Information on parental smoking status was extracted from a survey of JECS for children aged 1.5 years and data for serum 25(OH)D concentrations were obtained from blood tests in the Sub-Cohort Study of JECS performed at age 2 years. Logistic regression and linear models were fitted to evaluate the association between these variables. Data were analyzed for 4593 children. After adjusting for covariates, smoke exposure was significantly associated with increased incidence of VDD (OR 1.35; 95% CI, 1.14–1.59) according to the logistic model. The linear model indicated that passive smoking negatively predicted de-seasonalized serum 25(OH)D concentrations (β −0.5; 95% CI −0.95 to −0.08) in children aged 2 years. The results suggest that smoke exposure is a risk factor for VDD in children. Given that VD plays a crucial role in bone metabolism and the immune system, our findings are significant for clinical and public health.     

Vitamin D and Cancer: An Historical Overview of the Epidemiology and Mechanisms

This is a narrative review of the evidence supporting vitamin D’s anticancer actions. The first section reviews the findings from ecological studies of cancer with respect to indices of solar radiation, which found a reduced risk of incidence and mortality for approximately 23 types of cancer. Meta-analyses of observational studies reported the inverse correlations of serum 25-hydroxyvitamin D [25(OH)D] with the incidence of 12 types of cancer. Case-control studies with a 25(OH)D concentration measured near the time of cancer diagnosis are stronger than nested case-control and cohort studies as long follow-up times reduce the correlations due to changes in 25(OH)D with time. There is no evidence that undiagnosed cancer reduces 25(OH)D concentrations unless the cancer is at a very advanced stage. Meta-analyses of cancer incidence with respect to dietary intake have had limited success due to the low amount of vitamin D in most diets. An analysis of 25(OH)D-cancer incidence rates suggests that achieving 80 ng/mL vs. 10 ng/mL would reduce cancer incidence rates by 70 ± 10%. Clinical trials have provided limited support for the UVB-vitamin D-cancer hypothesis due to poor design and execution. In recent decades, many experimental studies in cultured cells and animal models have described a wide range of anticancer effects of vitamin D compounds. This paper will review studies showing the inhibition of tumor cell proliferation, dedifferentiation, and invasion together with the sensitization to proapoptotic agents. Moreover, 1,25-(OH)₂D₃ and other vitamin D receptor agonists modulate the biology of several types of stromal cells such as fibroblasts, endothelial and immune cells in a way that interferes the apparition of metastases. In sum, the available mechanistic data support the global protective action of vitamin D against several important types of cancer.