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.     

Dietary vitamin D intake is not associated with 25-hydroxyvitamin D3 or parathyroid hormone in elderly subjects,whereas the calcium-to-phosphate ratio affects parathyroid hormone

This cross-sectional study investigates whether serum 25-hydroxyvitamin D₃ [25(OH)D₃] and intact parathyroid hormone (iPTH) are affected by vitamin D, calcium, or phosphate intake in 140 independently living elderly subjects from Germany (99 women and 41 men; age, 66-96 years). We hypothesized that habitual dietary intakes of vitamin D, calcium, and phosphate are not associated with 25(OH)D₃ or iPTH and that body mass index confounds these associations. Serum 25(OH)D₃ and iPTH were measured by an electrochemiluminescence immunoassay. Dietary intake was determined using a 3-day estimated dietary record. The median dietary intake levels of vitamin D, calcium, and phosphate were 3 μg/d, 999 mg/d, and 1250 mg/d, respectively. Multiple regression analyses confirmed that dietary vitamin D and calcium did not affect 25(OH)D₃ or iPTH; however, supplemental intakes of vitamin D and calcium were associated with 25(OH)D₃ after adjustment for age, sex, body composition, sun exposure, physical activity, and smoking. In addition, phosphate intake and the calcium-to-phosphate ratio were associated with iPTH after multiple adjustments. In a subgroup analysis, calcium and vitamin D supplements, as well as phosphate intake, were associated with 25(OH)D₃ and/or iPTH in normal-weight subjects only. Our results indicate that habitual dietary vitamin D and calcium intakes have no independent effects on 25(OH)D₃ or iPTH in elderly subjects without vitamin D deficiency, whereas phosphate intake and the calcium-to-phosphate ratio affect iPTH. However, vitamin D and calcium supplements may increase 25(OH)D₃ and decrease iPTH, even during the summer, but the impact of supplements may depend on body mass index.     

Factors Associated with Serum Vitamin D Metabolites and Vitamin D Metabolite Ratios in Premenopausal Women

The most representative indicator of vitamin D status in clinical practice is 25(OH)D₃, but new biomarkers could improve the assessment of vitamin D status and metabolism. The objective of this study is to investigate the association of serum vitamin D metabolites and vitamin D metabolite ratios (VMRs) with potentially influential factors in premenopausal women. This is a cross-sectional study based on 1422 women, aged 39–50, recruited from a Madrid Medical Diagnostic Center. Participants answered an epidemiological and a food frequency questionnaire. Serum vitamin D metabolites were determined using an SPE–LC–MS/MS platform. The association between participant’s characteristics, vitamin D metabolites, and VMRs was quantified by multiple linear regression models. Mean 25(OH)D₃ concentration was 49.2 + 18.9 nmol/L, with greater deficits among obese, nulliparous, dark-skinned women, and with less sun exposure. A lower R2 ratio (1,25(OH)₂D₃/25(OH)D₃) and a higher R4 (24,25(OH)₂D₃/1,25(OH)₂D₃) were observed in nulliparous women, with high sun exposure, and those with low caloric intake or high consumption of calcium, vitamin D supplements, or alcohol. Nulliparous women had lower R1 (25(OH)D₃/Vit D₃) and R3 (24,25(OH)₂D₃/25(OH)D₃), and older women showed lower R3 and R4. Vitamin D status modified the association of the VMRs with seasons. VMRs can be complementary indicators of vitamin D status and its endogenous metabolism, and reveal the influence of certain individual characteristics on the expression of hydroxylase enzymes.     

Association between Circulating Levels of 25-Hydroxyvitamin D3 and Matrix Metalloproteinase-10 (MMP-10) in Patients with Type 2 Diabetes

Background: Matrix metalloproteinase-10 (MMP-10) levels increase progressively starting from early diabetic kidney disease (DKD) stages. Vitamin D₃ (vitD₃) deficit is associated with a higher risk of diabetic microangiopathy. Reduced MMP-10 expression has been observed after exposure to vitD₃. Aim: to assess how vitD₃ status is related to MMP-10 levels in patients with Type 2 diabetes (T2D). Methods: 256 patients with T2D were included in this cross-sectional study. Demographic, clinical and serum MMP-10 and 25-hydroxyvitamin D₃ (25(OH)D₃) levels were collected from each patient. The association between MMP-10 and (25(OH)D₃) levels was assessed using a correlation analysis and fitting a multivariate linear regression model. Results: Serum MMP-10 levels were inversely correlated with circulating 25(OH)D₃ (rho = −0.25; p < 0.001). In the subgroup analysis this correlation was significant in patients with DKD (rho = −0.28; p = 0.001) and in subjects with vitD₃ deficit (rho = −0.24; p = 0.005). In the regression model adjusted for kidney function, body adiposity, smoking and vitD supplementation MMP-10 levels were 68.7 pg/mL lower in patients with 25(OH)D₃ > 20 ng/mL, with respect to ≤20 ng/mL (p = 0.006). Conclusions: vitD₃ repletion status is an independent predictor of MMP-10 levels in T2D patients. Perhaps, high 25(OH)D₃ values should be targeted in these patients in order to prevent vascular complications.     

Effects of sun exposure and dietary vitamin D intake on serum 25-hydroxyvitamin D status in hemodialysis patients

BACKGROUND/OBJECTIVES

Vitamin D deficiency is common in hemodialysis patients. The aim of this study was to identify whether or not sun exposure and dietary vitamin D intake have effects on serum 25-hydroxyvitamin D (25(OH)D) status in hemodialysis (HD) patients. The objective was to identify the main determinants of serum vitamin D status in the study subjects.

SUBJECTS/METHODS

A cross-sectional study of 47 HD patients (19 males and 28 females) was performed. We assessed serum 25(OH)D and 1,25(OH)₂D levels between August and September 2012 and analyzed the prevalence of vitamin D deficiency in HD patients. To evaluate the determinants of serum 25(OH)D levels, we surveyed dietary vitamin D intake, degree of sun exposure, and outdoor activities. To compare biological variables, serum 25(OH)D was stratified as below 15 ng/ml or above 15 ng/ml.

RESULTS

Mean 25(OH)D and 1,25(OH)₂D levels were 13.5 ± 5.8 ng/ml and 20.6 ± 11.8 pg/ml, respectively. The proportions of serum 25(OH)D deficiency (< 15 ng/ml), insufficiency (15-< 30 ng/ml), and sufficiency (≥ 30 ng/ml) in subjects were 72.4%, 23.4%, and 4.3%, respectively. Prevalence of vitamin D deficiency in female patients was 78.6%, whereas that in males was 63.2% (P = 0.046). Vitamin D intake and sun exposure time were not significantly different between the two stratified serum 25(OH)D levels. Dietary intake of vitamin D did not contribute to increased serum 25(OH)D levels in HD patients. The main effective factors affecting serum 25(OH)D status were found to be the sun exposure and active outdoor exercise.

CONCLUSIONS

Hypovitaminosis D is common in HD patients and is higher in females than in males. Sun exposure is the most important determinant of serum 25(OH)D status in HD patients.     

A new method for the determination of vitamin D3 and 25-hydroxyvitamin D3 in meat

The total vitamin D content in meat, i.e., vitamin D₃ and 25-hydroxyvitamin D₃, was determined by HPLC after alkaline hydrolysation, solid-phase extraction and semi-preparative HPLC. For detection, a DAD detector between 220 and 320 nm was used and quantification was performed at 265 nm. Vitamin D₂ was used as internal standard for vitamin D₃ as well as for 25-hydroxyvitamin D₃. Precision for vitamin D₃ was determined in lean meat and lard to 9.1% and 7.1%, respectively. The corresponding values for 25-hydroxyvitamin D₃ were 8.9% and 9.9%. Accuracy was determined in spiked samples, which showed a recovery of 94.7% and 99.0% for vitamin D₃ and 25-hydroxyvitamin D₃, respectively. The method is applicable for establishing data for food composition tables.     

Intake of 25-Hydroxyvitamin D3 May Reduce the Severity of Upper Respiratory Tract Infection: Post hoc Analysis of a Randomized,Double-Blind,Placebo-Controlled,Parallel Group Comparison Study

To evaluate the effects of 25-hydroxyvitamin D₃ (25OHD) on symptoms at the onset of the upper respiratory tract infection (URTI) in subjects with insufficient or deficient serum 25-hydroxyvitamin D levels, we conducted a post hoc analysis of data from a randomized, placebo-controlled study; the subjects received 10 μg of 25OHD per day or a placebo for 16 weeks. The Wisconsin Upper Respiratory Symptom Survey-21 was used to determine URTI. The study endpoints included WURSS-21 scores, number of URTI events, and proportion of medication (antibiotics, antipyretic analgesics) usage. We found that the physical symptom scores for “Runny nose,” “Sneezing,” and “Head congestion” were significantly lower in the 25OHD group than in the placebo group; for all items except “Breathe easily, “the quality of life” scores were significantly improved in the 25OHD group. There was no significant difference in the number of URTI events or the proportion of medication use between the groups. Collectively, the findings of this study indicate that a sufficient 25OHD intake can reduce physical symptoms at the onset of upper respiratory tract infection, particularly nasal symptoms, and may improve the quality of life at the time of onset.     

Adequate Dietary Intake and Vitamin D Supplementation: A Study of Their Relative Importance in Determining Serum Vitamin D and Ferritin Concentrations during Pregnancy

Vitamin D is essential for human health. However, it is not clear if vitamin D supplementation is necessary for all pregnant women. This study examines the relative importance of dietary patterns and vitamin D supplementation frequency in determining serum 25-hydroxyvitamin D (25(OH)D) and ferritin concentrations among pregnant women in Hong Kong, China. A total of 572 healthy women were recruited from antenatal clinics at 25–35 weeks pregnant. Participants completed an electronic version of the food frequency questionnaire and a web questionnaire on supplement use. Their blood samples were tested for serum 25(OH)D and ferritin. The associations of dietary patterns and vitamin D supplementation frequency with serum 25(OH)D and ferritin concentrations were analyzed using moderated hierarchical regression. Two dietary patterns were identified. The adequate dietary intake was characterized by the high probability of meeting recommended daily food group servings, whereas the inadequate dietary intake was characterized by inadequate consumption of vegetables, fruits, meat, fish, and eggs, or alternatives. The association between adequate dietary intake and serum ferritin concentrations was independent of vitamin D supplementation frequency (β = 0.05, p = 0.035), but dietary patterns interacted with vitamin D supplementation frequency to determine serum 25(OH)D concentrations (β = −13.22, p = 0.014). The current study presents evidence on the relative importance of dietary patterns and vitamin D supplementation in maintaining sufficient vitamin D and iron in pregnancy. Antenatal nutrition counselling services should be provided to pregnant women who show signs of inadequate dietary intake.     

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.     

The Impact of Sample Type on Vitamin D Quantification and Clinical Classification during Pregnancy

Measurement of vitamin D status has significant use in clinical and research settings, including during pregnancy. We aimed to assess the agreement of total 25-hydroxyvitamin D (25(OH)D) concentration, and its three analytes (25-hydroxyvitamin D₃ (25(OH)D₃), 25-hydroxyvitamin D₂ (25(OH)D₂) and Epi-25-hydroxyvitamin D₃ (Epi-25(OH)D₃)), in plasma and serum samples collected during pregnancy, and to examine the proportion of women who change vitamin D status category based on sample type. Matching samples were collected from n = 114 non-fasting women between 12–25 weeks gestation in a clinical trial in Newcastle, Australia. Samples were analysed by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) to quantify total 25(OH)D and its analytes and examined using Bland-Altman plots, Pearson correlation (r), intraclass correlation coefficient and Cohen’s Kappa test. Serum total 25(OH)D ranged from 33.8–169.8 nmol/L and plasma ranged from 28.6–211.2 nmol/L. There was a significant difference for total 25(OH)D based on sample type (measurement bias 7.63 nmol/L for serum vs plasma (95% Confidence Interval (CI) 5.36, 9.90, p ≤ 0.001). The mean difference between serum and plasma concentrations was statistically significant for 25(OH)D₃ (7.38 nmol/L; 95% CI 5.28, 9.48, p ≤ 0.001) and Epi-25(OH)D₃ (0.39 nmol/L; 95% CI 0.14, 0.64, p = 0.014). Of 114 participants, 28% were classified as vitamin D deficient (<50 nmol/L) or insufficient (<75 nmol/L) based on plasma sample and 36% based on serum sample. Nineteen (16.7%) participants changed vitamin D status category based on sample type. 25-hydroxyvitamin D quantification using LC-MS/MS methodology differed significantly between serum and plasma, yielding a higher value in plasma; this influenced vitamin D status based on accepted cut-points, which may have implications in clinical and research settings.     

Plasma 25-Hydroxyvitamin D Responses of Younger and Older Men to Three Weeks of Supplementation with 1800 IU/day of Vitamin D

Objective: The objective of this study was to compare changes in plasma 25-hydroxyvitamin D (25(OH)D) levels of younger and older men after three weeks of oral vitamin D supplementation.

Methods: Nine younger men (22 to 28 years) and nine older men (65 to 73 years) with self-reported vitamin D intakes below 200 IU/d were enrolled in February and randomized to 1800 IU/d of ergocalciferol (vitamin D₂, n=11) or to a control group (n=7) and followed for three weeks. Blood was collected at baseline, and after one, two and three weeks for measurement of plasma concentrations of total 25(OH)D, 25(OH)D₂ and 25(OH)D₃.

Results: In both the younger and older supplemented men, 25(OH)D₂ and total 25(OH)D concentrations increased significantly during the study, whereas values of these metabolites did not change in younger or older control subjects. No group showed significant changes in 25-hydroxyvitamin D₃. There was a significant interaction between age group and supplement group, suggesting that the effect of vitamin D₂ supplementation on changes in 25(OH)D₂ changes with age. The mean increase in 25(OH)D₂ was greater in the younger supplemented men than in the older supplemented men (37±9 nmol/L vs. 19.5 nmol/L, p=0.027), and this accounted for their significantly greater increase in total 25(OH)D.

Conclusion: These data are consistent with an age-related decline in the absorption, transport or liver hydroxylation of orally-consumed vitamin D.     

极低出生体重早产儿血清磷、骨碱性磷酸酶、25-羟基维生素D水平动态变化分析

目的 调查分析极低出生体重早产儿血清磷(P)、骨碱性磷酸酶(BALP)、25-羟基维生素D[25-(OH)D₃]水平动态变化,为临床早产儿代谢性骨病的早期预防提供指导。方法 选择入住烟台山医院新生儿科病房且符合入选标准的110例新生儿为研究对象,其中极低出生体重早产儿60例(病例组),足月产儿50例(对照组),分别于出生后1、4、12周空腹采取静脉血2 ml,测定血清P、BALP、25-(OH)D₃水平,分析骨代谢指标的变化情况。结果 病例组25-(OH)D₃水平增长速度低于对照组;两组血清P水平无明显变化。与对照组比较,病例组出生后1、4、12周血清BALP水平均显著性偏高;出生后第12周25-(OH)D₃水平的差异有统计学意义,其中病例组异常率达26.7%,对照组异常率为0。结论 极低出生体重早产儿(病例组)出生后追赶性生长过程中血清BALP、25-(OH)D₃水平与足月儿(对照组)有明显差异,提示该两项指标检测有助于极低出生体重儿代谢性骨病的早期发现及干预,其中以血清BALP指标敏感性较好。     

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.     

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.     

Serum Levels of Vitamin D and Dental Caries in 7-Year-Old Children in Porto Metropolitan Area

Vitamin D deficiency has been associated with significant changes in dental structures. In children, it can induce enamel and dentin defects, which have been identified as risk factors for caries. This study aimed to assess the association between low serum 25-hydroxyvitamin D (25(OH) D) levels (<30 ng/mL) and the prevalence of caries in the permanent teeth and mixed dentition of 7-year-old children. A sample of 335 children from the population-based birth cohort Generation XXI (Porto, Portugal) was included. Data on children’s demographic and social conditions, health status, dental health behaviours, dental examination including erupted permanent first molars, and blood samples available for vitamin D analysis were collected. Dental outcomes included the presence of caries, including non-cavitated lesions (d_1–6mft/D_1–6MFT > 0), and advanced caries (d_3–6mft/D_3–6MF > 0). Serum 25(OH) D was measured using a competitive electrochemiluminescence immunoassay protein-binding assay. Bivariate analysis and multivariate logistic regression were used. Advanced caries in permanent teeth was significantly associated with children’s vitamin D levels <30 ng/mL, gastrointestinal disorders, higher daily intake of cariogenic food, and having had a dental appointment at ≤7 years old. Optimal childhood levels of vitamin D may be considered an additional preventive measure for dental caries in the permanent dentition.     

Relative concentrations of 25-hydroxyvitamin D2/D3 and 1,25-dihydroxyvitamin D2/D3 in maternal plasma at delivery

Quantitation of circulating 25-OH-D₂, 25-OH-D₃, 1,25-(OH)₂-D₂ and 1,25-(OH)₂-D₃ was performed on the plasma from 10 women collected at delivery following full term pregnancies. These data indicate that approximately 50% of the circulating 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in these women are in the vitamin D₂ form. Further, they demonstrate that vitamin D₂ contributes significantly to the total vitamin D status of these individuals and cannot be considered of trivial importance. It is apparent from this study that assay techniques which specifically quantitate vitamin D₂, as well as D₃ must be employed when measuring the total vitamin D status of individuals who are consuming significant quantities of dietary vitamin D₂.     

Association between Intake of Sugar-Sweetened Beverages and Circulating 25-Hydroxyvitamin D Concentration among Premenopausal Women

Intake of sugar-sweetened beverages has increased in North America and seems to have several adverse health effects possibly through decreased circulating 25-hydroxyvitamin D (25(OH)D) concentrations. The aim of this cross-sectional study was to evaluate the association between sugar-sweetened beverages intake and 25(OH)D concentrations among premenopausal women. Intake of sugar-sweetened beverages including colas, other carbonated beverages and sweet fruit drinks was assessed using a validated food frequency questionnaire among 741 premenopausal women. Plasma concentrations of 25(OH)D were quantified by radioimmunoassay. The association between sugar-sweetened beverages intake and 25(OH)D concentrations was evaluated using multivariate generalized linear models and Spearman correlations. A higher intake of colas was associated with lower mean 25(OH)D levels (67.0, 63.7, 64.7 and 58.5 nmol/L for never, <1, 1–3 and >3 servings/week, respectively; r = −0.11 (p = 0.004)). A correlation was observed between intake of other carbonated beverages and 25(OH)D concentrations but was not statistically significant (r = −0.06 (p = 0.10)). No association was observed between intake of sweet fruit drinks and 25(OH)D concentrations. This study suggests that high intake of colas may decrease 25(OH)D levels in premenopausal women. Considering the high consumption of these drinks in the general population and the possible consequences of vitamin D deficiency on health, this finding needs further investigation.     

Association between Subcutaneous White Adipose Tissue and Serum 25-Hydroxyvitamin D in Overweight and Obese Adults

Cholecalciferol is known to be deposited in human adipose tissue, but it is not known whether 25-hydroxyvitamin D (25(OH)D) is found in detectable concentrations. Therefore, our objective was to determine whether 25(OH)D is detectable in subcutaneous white adipose tissue (SWAT) in overweight and obese persons enrolled in a twelve week energy restricted diet. Baseline and post-intervention gluteal SWAT biopsies were collected from 20 subjects participating in a larger clinical weight loss intervention. LC-MS/MS was utilized to determine SWAT 25(OH)D concentrations. Serum 25(OH)D and 1,25(OH)₂D were measured by RIA. Body composition was assessed by dual energy x-ray absorptiometry. SWAT 25(OH)D concentrations were 5.8 ± 2.6 nmol/kg tissue and 6.2 ± 2.7 nmol/kg tissue pre- and post-intervention SWAT, respectively. There was a significant positive association between SWAT 25(OH)D concentration and serum 25(OH)D concentration (r = 0.52, P < 0.01). Both SWAT and serum 25(OH)D concentrations did not significantly change after a twelve-week period of energy restriction with approximately 5 kg of fat loss. In conclusion, we have demonstrated our LC-MS/MS method can detect 25(OH)D₃ in human subcutaneous fat tissue from overweight and obese individuals and is consistent with previously reported concentrations in swine. Additionally, our findings of no significant changes in SWAT 25(OH)D₃ or serum 25(OH)D after a 6% loss of total body weight and 13% reduction in total fat provides the first human evidence that adipose 25(OH)D does not likely contribute to serum 25(OH)D with moderate weight loss; whether this is also the case with larger amounts of weight loss is unknown. Weight loss alone is not sufficient to increase serum 25(OH)D and increases in dietary or dermal biosynthesis of vitamin D appear to be the most critical contributors to in vitamin D status.     

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.