Plasma 25OHD Research Articles

Expression of vitamin D receptor and 1α‐hydroxylase in epicardial fat: association to plasma 25‐hydroxyvitamin D level in coronary artery disease patients (1139.8)

25‐hydroxyvitamin D (25OHD) is the main circulating vitamin D form and 1α‐hydroxylase (CYP27B1) is the key enzyme which activates 25OHD in tissues. In adipose tissue, reduced vitamin D and increased vitamin D receptor (VDR) levels have been associated to fat accumulation and inflammation.Alterations in epicardial fat (EAT) biology (i.e. increased fat thickness and inflammation) have been described in patients with coronary artery disease (CAD) but it is unknown whether low plasma level of 25OHD and/or inadequate levels of VDR and CYP27B1 at EAT level may contribute to these EAT functional alterations.Our aim was to evaluate in CAD patients the relationship between plasma 25OHD level and gene expression of VDR and CYP27B1 at EAT level.Plasma 25OHD was quantified by an immunoluminometric assay. Gene expression was performed by microarray.CAD patients had low 25OHD level. After patient stratification according to 25OHD level, we observed increased expression of VDR and reduced expression of CYP27B1 at EAT level only in patients with 25OHD deficiency (< 20 ng/mL) and insufficiency (20‐30 ng/mL).We may conclude that in CAD patients, EAT tries to compensate reduced plasma 25OHD level by increasing VDR expression. Anyway, due to the impairment in 25OHD activation, the local vitamin availability seems to be reduced. How this may contribute to EAT functional alterations observed in CAD needs further investigation.Grant Funding Source: Supported by DiaSorin S.P.A., Vercelli, Italy

Interpretation of Plasma PTH Concentrations According to 25OHD Status, Gender, Age, Weight Status, and Calcium Intake: Importance of the Reference Values

Reference values for plasma PTH assessment were generally established on small samples of apparently healthy subjects, without considering their 25-hydroxyvitamin D (25OHD) status or other potential modifiers of PTH concentration. Our objective was to assess ranges of plasma PTH concentration in a large sample of adults, stratifying by 25OHD status, age, gender, weight status, and calcium intake. This cross-sectional survey is based on 1824 middle-aged Caucasian adults from the Supplémentation en Vitamines et Minéraux Antioxydants study (1994). Plasma PTH and 25OHD concentrations were measured by an electrochemoluminescent immunoassay. Extreme percentiles of plasma PTH concentrations were assessed specifically in subjects who had plasmatic values of 25OHD of 20 ng/mL or greater and 30 ng/mL or greater. Among subjects with 25OHD status of 20 ng/mL or greater, the 97.5th percentile of plasma PTH concentration was 45.5 ng/L. By using this value as a reference, 5% of the subjects with plasma 25OHD less than 20 nmol/L had a high plasma PTH level, reflecting secondary hyperparathyroidism. Among vitamin D-replete subjects (25OHD status of 20 ng/mL or greater), the 97.5th percentile of plasma PTH was higher in overweight/obese subjects (51.9 vs 43.5 ng/L among normal weight subjects). The reference value for plasma PTH defined in this vitamin D-replete population was far below the value currently provided by the manufacturer (65 ng/L) and varied according to overweight status. These results may contribute to improve the diagnosis of primary and secondary hyperparathyroidism and subsequent therapeutic indication.

Vitamin D status was not associated with ‘one-year’ progression of coronary artery disease, assessed by coronary angiography in statin-treated patients

Low vitamin D status is associated with increased risk of cardiovascular disease and may be involved in atherosclerosis. Our aim was to assess the association between vitamin D status and the progression of coronary artery disease (CAD). We measured 25-hydroxyvitamin D3 (25OHD3) by liquid chromatography tandem mass spectrometry (LC-MS/MS) in plasma from 348 participants with established CAD (84% males, mean ± standard deviation (SD) age 60 ± 10 years) of the Western Norway B-vitamin Intervention Trial (WENBIT, 1999-2006). The patients underwent invasive coronary angiography (CA) and percutaneous coronary intervention at baseline and a second CA after 302 ± 79 days of follow-up. From the angiograms, minimal lumen diameter (MLD) and diameter stenosis (DS) of atherosclerotic lesions were obtained. Significant CAD in non-intervened vessels was found in 309 coronary arteries from 183 participants either at baseline and/or at follow-up. To assess the association between levels of 25OHD3 and CAD progression in non-intervened vessels, we applied a linear quantile fitted mixed effects model with MLD or DS measured at follow-up as a function of continuous 25OHD3 concentrations. There were no statistically significant associations between plasma 25OHD3 concentrations (median: 63.9, 95% confidence interval (CI): 48.1-78.5 nmol/l) measured at baseline and the follow-up measures of either MLD (estimated effect per 10 nmol/l increase of 25OHD3 and 95% CI: -0.015 (-0.032-0.002) mm, p = 0.088) or DS (0.225 (-0.354-0.804) percentage points, p = 0.444). Multivariate adjustment did not alter these results. Plasma 25OHD3 levels were not associated with 'one-year' progression of CAD, assessed by CA in statin-treated patients.

Plasma 25-hydroxyvitamin D and risk of metabolic syndrome: an ancillary analysis in the Diabetes Prevention Program.

Low blood levels of 25-hydroxyvitamin D (25OHD) have been associated with cardiometabolic disease but results are inconsistent. The objective of the study was to investigate the association of 25OHD with metabolic syndrome in a population at increased risk for diabetes. Using baseline data from the placebo and lifestyle intervention arms of the Diabetes Prevention Program (N=2000), multivariable logistic regression models were used to estimate the odds of prevalent metabolic syndrome and each of its individual components across 25OHD tertiles. Multivariable linear regression was used to estimate the adjusted mean difference of insulin secretion and sensitivity across the same 25OHD tertiles. In participants free of metabolic syndrome at baseline (N=546), incident metabolic syndrome in the first 2 years of follow-up was assessed using discrete-time proportional hazards regression to test its association with 25OHD concentration. After multivariate adjustment, participants in the highest tertile of 25OHD had lower odds of prevalent metabolic syndrome (odds ratio=0.62; 95% confidence interval (CI)=0.45-0.84), smaller waist circumference, higher high-density lipoprotein and lower fasting plasma glucose compared with participants in the lowest tertile of 25OHD. Higher plasma 25OHD concentration was associated with greater insulin sensitivity and lower insulin secretion. After multivariate adjustment, there was a nonsignificant lower risk of metabolic syndrome in the highest tertile of 25OHD (hazard ratio=0.79; 95% CI=0.48-1.32) compared with the lowest tertile. In a population at increased risk for diabetes, higher plasma 25OHD concentration was inversely associated with prevalent metabolic syndrome and nonsignificantly with incident metabolic syndrome.

Adiposity and the relationship between vitamin D and blood pressure

ObjectiveCirculating vitamin D (25OHD) concentrations are negatively associated with blood pressure (BP) but little is known about the mechanisms for this relationship. Adiposity is positively associated with BP and inversely with circulating 25OHD concentrations but no studies have assessed the relationship between plasma 25OHD and adiposity on BP. The goal of this study is to investigate if the association between plasma 25OHD and BP is mediated by adiposity. Materials/MethodsThe relationship between plasma 25OHD, systolic and diastolic BP, and adiposity [BMI, waist circumference, visceral adipose tissue (VAT)] was assessed in a multi-ethnic cross-sectional study of Aboriginal (n=151), Chinese (n=190), European (n=170), and South Asian (n=176) participants by linear regression models. ResultsPlasma 25OHD concentrations were negatively associated with systolic (standardized B=−0.191, P<0.001) and diastolic BP (standardized B=−0.196, P<0.001) in models adjusted for age, sex, ethnicity, family history of CVD, smoking status, alcohol consumption, and physical activity. The negative relationship between plasma 25OHD concentrations and systolic and diastolic BP was attenuated after the addition of BMI, waist circumference, and VAT to the models, but the relationship remained significant. Plasma 25OHD concentrations accounted for 0.7% and 0.8% of the variance in systolic and diastolic BP, respectively. ConclusionThese findings suggest that the relationship between vitamin D and BP is independent of adiposity. Further studies are required to determine the mechanisms by which vitamin D affects BP.

Hip fracture risk factors and the discriminability of hip fracture risk vary by age: A case–control study

To determine the important risk factors for hip fracture and the discriminability of hip fracture risk in different age cohorts (≤80 years, >80 years). Consecutive admissions of hip fracture over 24 months in those aged >60 years, and an age- and sex-matched control derived from admissions under a medical unit were prospectively assessed. The risk factors and the discriminabilty of hip fracture risk by age were investigated for each sex in univariate and multivariate models. The area under the curve (AUC) statistics from the receiver operating characteristic curve analysis was used to estimate the ability of the independent risk factors to discriminate hip fracture risk. The important risk factors in women aged ≤80 years were lower bodyweight, previous osteoporotic fracture, hip fracture in first-degree relatives and lower plasma 25OHD, and their discriminative effect was (AUC) 0.69. Previous osteoporotic fracture and lower plasma 25OHD were the important risk factors in men aged ≤80 years, with a discriminative effect of 0.83. In the >80-year age cohorts, only falls was independently associated with hip fracture in both sexes, with discriminative effects of 0.60 and 0.62 in females and males, respectively. The overall discrimination of hip fracture risk appears less adequate in those aged >80 years when compared with those aged ≤80 years. Although skeletal factors have a greater risk association with hip fracture in patients aged ≤80 years, it is falls that is important in those aged >80 years. The relative importance of risk factors also appears to vary between the sexes in those aged ≤80 years.

SAT0355 Vitamin D3 status and dress style of women in the sunny UAE

BackgroundVitamin D deficiency is attributed to several causes including the lack of adequate exposure to sunlight due to the clothing styles that hinder the effect of UVB on skin synthesis...

The Effect of High-Dose Vitamin D Supplementation on Calciotropic Hormones and Bone Mineral Density in Obese Subjects with Low Levels of Circulating 25-Hydroxyvitamin D: Results from a Randomized Controlled Study

Low levels of 25-hydroxyvitamin D (25OHD) are associated with increased bone turnover and risk of fractures. Plasma 25OHD is inversely related to body mass index, and vitamin D deficiency is common in obesity. We aimed to determine whether vitamin D supplementation affects bone turnover and bone mineral density (BMD) in obese subjects. Fifty-two healthy obese men and women aged 18-50 years with plasma 25OHD levels below 50 nmol/L were randomized to 7,000 IU of cholecalciferol daily or placebo for 26 weeks. We measured plasma levels of 25OHD, parathyroid hormone (PTH), and markers of bone turnover, as well as BMD at the hip, spine, forearm, and whole body. Compared with placebo, treatment with cholecalciferol increased mean plasma 25OHD from 35 to 110 nmol/L (p < 0.00001) and significantly decreased PTH (p < 0.05). BMD increased significantly at the forearm by 1.6 ± 0.7 % (p = 0.03). The bone resorption marker C-terminal telopetide of type 1 collagen (CTX) decreased borderline significantly in the cholecalciferol group compared with the placebo group (p = 0.07). Changes in plasma 25OHD correlated inversely with changes in plasma levels of bone-specific alkaline phosphatase (r = -0.38, p = 0.01) and CTX (r = -0.33, p = 0.03). Changes in CTX correlated inversely with changes in spine BMD (r = -0.45, p = 0.04). Increasing circulating 25OHD levels by cholecalciferol treatment is of importance to bone health in young obese subjects as increased levels of 25OHD are associated with a decrease in both PTH and bone turnover and with an increase in BMD at the forearm.

Effects of vitamin D supplementation on body fat accumulation, inflammation, and metabolic risk factors in obese adults with low vitamin D levels — Results from a randomized trial

BackgroundLow plasma 25-hydroxy-vitamin D (25OHD) is associated with obesity. Vitamin D (VD) may be implicated in obesity and its complications such as insulin resistance, hypertension, and low-grade inflammation. We investigated the effects of VD supplementation on fat distribution and on obesity complications in obese adults with low plasma levels of 25OHD. MethodsIn a double-blind design 52 subjects aged 18 to 50years with BMI>30kg/m2 and plasma 25OHD <50nmol/l were randomized to 26weeks of treatment with 7000IU of VD daily or placebo. Body composition was assessed by DXA and subcutaneous (SAT) and visceral adipose tissue (VAT), intrahepatic (IHL) and intramyocellular lipids (IMCL) were evaluated by magnetic resonance imaging and magnetic resonance spectroscopy. Insulin resistance (HOMA-IR), blood pressure, plasma lipids, and circulating inflammatory markers were also investigated. ResultsVD treatment increased mean plasma levels of 25OHD from 33nmol/l to 110nmol/l (P<0.0001) and decreased median parathyroid hormone levels from 5.3 to 4.5pmol/l (P<0.01) in the intervention group. Treatment did not change body fat, SAT, VAT, IHL, or IMCL compared with placebo. Neither did treatment affect HOMA, blood pressure, plasma lipids or any of several inflammatory markers investigated including hsCRP. ConclusionIncreasing 25OHD levels by VD treatment for 26weeks have no effects on obesity complications in obese adults with low baseline plasma 25OHD.

Vitamin D Insufficiency is Associated with Greater Obesity‐Related Insulin Resistance

Insulin resistance (IR) and vitamin D insufficiency [circulating 25‐hydroxyvitamin D (25OHD) ≤50nmol/L] are associated with obesity (BMI≥30kg/m2). We reported that visceral adipose tissue (VAT) is a negative determinant of plasma 25OHD. Given that vitamin D may play a role in insulin sensitivity the goal of this study is to explore the association between a vitamin D insufficiency/obesity phenotype with IR in healthy adults (N=364). Subjects were assessed for socio‐demographics; anthropometrics; body fat distribution; fasting plasma glucose, insulin, and 25OHD; and the homeostasis model assessment (HOMA) of IR. Subjects were grouped as: vitamin D adequate/no obesity; vitamin D adequate/obesity; vitamin D insufficiency/no obesity; and vitamin D insufficiency/obesity. Data were analyzed by linear regression adjusted for age, sex, ethnicity, smoking, physical activity, season, and VAT. Vitamin D insufficiency/obesity was observed in 20% of subjects and HOMA‐IR was 21% higher [B=0.207; p=0.033] in these subjects than those in the vitamin D adequate/no obesity group. No associations were observed between HOMA‐IR and adequate vitamin D/obesity or vitamin D insufficiency/no obesity groups. These findings suggest that vitamin D insufficiency in subjects with obesity places them at greater risk for IR, even after adjusting for body fat distribution. Vitamin D may play a role in obesity‐related IR.

Effects of vitamin C and vitamin D on mood and distress in acutely hospitalized patients

Hypovitaminosis C and D are highly prevalent in acute‐care hospitals, but their clinical implications have not been investigated. Because deficiencies of these vitamins can adversely affect mood, we conducted a double‐blind randomized clinical trial to determine the effect of vitamin C (500 mg twice daily) or D (5000 IU daily) supplementation on psychological status, as assessed using two different validated instruments. At baseline, 73% of patients had a subnormal plasma vitamin C concentration (&lt; 28.4 μM) and 79% had a subnormal plasma 25OHD concentration (&lt; 75 nM). Vitamin C provision for a mean of 8.2 days (n = 26) normalized plasma vitamin C concentrations (P &lt; 0.0001) and resulted in a 71% reduction in Profile of Mood StatesR total mood disturbance score (from 24.0 ± 18.2 to 6.9 ± 14.4, mean ± SD; P = 0.0002) and a 51% reduction in psychological distress as measured using the Distress Thermometer (from 4.5 ± 2.9 to 2.2 ± 2.2; P = 0.0002). By contrast, high‐dose vitamin D provision for a mean of 8.1 days (n = 26) increased plasma 25OHD concentrations (P &lt; 0.0001), but not into the normal range, and had statistically insignificant effects on mood (21.7 ± 17.3 to 14.6 ± 17.7; P = 0.067) and distress (3.7 ± 2.6 to 3.4 ± 2.8; P = 0.45).ConclusionHypovitaminosis C and D are highly prevalent in acutely hospitalized patients. Vitamin C supplementation improves mood and reduces distress in these patients. Supported by the Lotte and John Hecht Foundation and a Faculty of Medicine student research bursary.Grant Funding Source: Lotte and John Hecht Foundation

Vitamin D status in Greenland – dermal and dietary donations

BackgroundVitamin D status influences skeletal health, the risk of falls and fractures, and muscle health, and it has been associated with inflammatory, infectious, cardiovascular and metabolic disorders in addition to some cancers. Prevailing intracellular infections such as tuberculosis are speculated to relate to vitamin D status. The vitamin D sources are dietary and dermal, the latter depending on UVB radiation exposure from the sun. Life in the Arctic influences vitamin D status because of dietary peculiarities, the polar night, waning of the ozone layer and maybe ethnic differences between Inuit and non-Inuit.Objective and designData on vitamin D status as estimated by plasma 25OHD in Inuit and non-Inuit in Greenland are reviewed.ResultsDecreasing intake of vitamin D-rich local food items associated with decreasing plasma 25OHD levels and insufficient vitamin D status is seen with low intake of traditional Inuit foods. Plasma 25OHD levels increase markedly during spring and summer in parallel with the high influx of sunlight while plasma 25OHD is not influenced by obesity in Greenland Inuit and no clear-cut association is seen between plasma 25OHD and the risk of tuberculosis.ConclusionThe frequency of vitamin D deficiency in populations in Greenland rises with the dietary transition and diseases related to low vitamin D status should be monitored.

Vitamin D supplementation in older people (VDOP): Study protocol for a randomised controlled intervention trial with monthly oral dosing with 12,000 IU, 24,000 IU or 48,000 IU of vitamin D3

The randomised, double blind intervention trial ‘Optimising Vitamin D Status in Older People’ (VDOP) will test the effect of three oral dosages of vitamin D given for one year on bone mineral density (BMD) and biochemical markers of vitamin D metabolism, bone turnover and safety in older people. VDOP is funded by Arthritis Research UK, supported through Newcastle University and MRC Human Nutrition Research and sponsored by the Newcastle upon Tyne Hospitals NHS Foundation Trust.aBackgroundVitamin D insufficiency is common in older people and may lead to secondary hyperparathyroidism, bone loss, impairment of muscle function and increased risk of falls and fractures. Vitamin D supplementation trials have yielded conflicting results with regard to decreasing rates of bone loss, falls and fractures and the optimal plasma concentration of 25 hydroxy vitamin D (25OHD) for skeletal health remains unclear.Method/designOlder (≥70 years) community dwelling men and women are recruited through General Practices in Northern England and 375 participants are randomised to take 12,000 international units (IU), 24,000 IU or 48,000 IU of vitamin D3 orally each month for one year starting in the winter or early spring. Hip BMD and anthropometry are measured at baseline and 12 months. Fasting blood samples are collected at baseline and three-month intervals for the measurement of plasma 25OHD, parathyroid hormone (PTH), biochemical markers of bone turnover and biochemistry to assess the dose–response and safety of supplementation. Questionnaire data include falls, fractures, quality of life, adverse events and outcomes, compliance, dietary calcium intake and sunshine exposure.DiscussionThis is the first integrated vitamin D supplementation trial in older men and women using a range of doses given at monthly intervals to assess BMD, plasma 25OHD, PTH and biochemical markers of bone turnover and safety, quality of life and physical performance. We aim to investigate the vitamin D supplementation and plasma 25OHD concentration required to maintain bone health and to develop a set of biochemical markers that reflects the effect of vitamin D on bone. This will aid future studies investigating the effect of vitamin D supplementation on fracture risk.#ISRCTN 35648481 (assigned 16 August 2012), EudraCT 2011-004890-10.

Circulating 25OHD, Dietary Vitamin D, PTH, and Calcium Associations with Incident Cardiovascular Disease and Mortality: The MIDSPAN Family Study

Observational studies relating circulating 25-hydroxyvitamin D (25OHD) and dietary vitamin D intake to cardiovascular disease (CVD) have reported conflicting results. Our objective was to investigate the association of 25OHD, dietary vitamin D, PTH, and adjusted calcium with CVD and mortality in a Scottish cohort. The MIDSPAN Family Study is a prospective study of 1040 men and 1298 women from the West of Scotland recruited in 1996 and followed up for a median 14.4 yr. Locally resident adult offspring of a general population cohort were recruited from 1972-1976. CVD events (n = 416) and all-cause mortality (n = 100) were evaluated. 25OHD was measured using liquid chromatography-tandem mass spectrometry in available plasma (n = 2081). Median plasma 25OHD was 18.6 ng/ml, and median vitamin D intake was 3.2 μg/d (128 IU/d). Vitamin D deficiency (25OHD <15 ng/ml) was present in 689 participants (33.1%). There was no evidence that dietary vitamin D intake, PTH, or adjusted calcium were associated with CVD events or with mortality. Vitamin D deficiency was not associated with CVD (fully adjusted hazard ratio = 1.00; 95% confidence interval = 0.77-1.31). Results were similar after excluding patients who reported an activity-limiting longstanding illness at baseline (18.8%) and those taking any vitamin supplements (21.7%). However, there was some evidence vitamin D deficiency was associated with all-cause mortality (fully adjusted hazard ratio = 2.02; 95% confidence interval = 1.17-3.51). Vitamin D deficiency was not associated with risk of CVD in this cohort with very low 25OHD. Future trials of vitamin D supplementation in middle-aged cohorts should be powered to detect differences in mortality outcomes as well as CVD.

Should We Be Recommending Vitamin D Supplementation for Hypertension and Cardiovascular Disease Prevention?

Should We Be Recommending Vitamin D Supplementation for Hypertension and Cardiovascular Disease Prevention?

The association between plasma 25-hydroxyvitamin D3 concentrations, C-reactive protein levels, and coronary artery atherosclerosis in postmenopausal monkeys

The aim of this study was to identify the potential relationships between plasma 25-hydroxyvitamin D(3) (25OHD(3)), C-reactive protein (CRP), coronary artery atherosclerosis (CAA), and coronary artery remodeling in monkeys consuming atherogenic diets. Female cynomolgus monkeys (n = 74) were fed a casein-lactalbumin (C/L)-based, moderately atherogenic diet for 12 months. They then consumed either a soy-based (n = 35) or C/L-based (n = 39) diet for 32 months. CRP concentrations were then determined, and monkeys underwent surgical menopause. Each diet group was then rerandomized to receive soy (n = 36) or C/L (n = 38). After 32 postmenopausal months, 25OHD(3), CRP, CAA, and coronary artery remodeling were determined. All monkeys received a woman's equivalent of 1,000 IU/day of vitamin D(3) and 1,200 mg/day of calcium throughout the study. The premenopausal and postmenopausal dietary protein sources had no effect on postmenopausal 25OHD(3) concentrations (P = 0.6). Across treatment groups, there was a statistically significant inverse relationship between 25OHD(3) concentrations and CRP at necropsy (r = -0.35, P = 0.003). A significant inverse correlation between 25OHD(3) concentration and the change in CRP from premenopause to postmenopause was observed (r = -0.32, P = 0.007). The significant associations identified between plasma 25OHD(3) and CRP remained after controlling for postmenopausal diet. Those monkeys with a greater increase in CRP also had significantly more CAA and less ability to maintain normal lumens by remodeling. Higher plasma concentrations of 25OHD(3) were associated with lower CRP. Lower CRP was associated with less coronary atherosclerosis and improved coronary artery remodeling. These findings suggest that 25OHD(3) concentrations are associated with an anti-inflammatory state and may support an association between oral vitamin D3 and cardioprotection.

Challenges in vitamin D analysis / Izazovi u analizi vitamina D

Summary Vitamin D is an important determinant for the regulation of calcium and phosphorus levels and mineralization of the bone. The most reliable indicator of vitamin D status is the measurement of plasma or serum 25OH-D concentration. Several studies reported discrepancies between the results of assays. These high variabilities in 25OH-D measurements are due to used assay technologies and lack of standardization against the reference materials. Different assays have been employed for the measurement of 25OHD levels: Competitive Protein Binding Assays, immunoassays, direct detection methods. Choosing an assay platform is important both for clinical laboratory professionals and researchers, and several factors affect this process. Recently, liquid chromatography and tandem mass spectrometry is an alternative method to traditional assays and provides higher specificity and sensitivity than many assays; therefore, it has been suggested as a candidate reference method for circulating 25OH-D3. Standardization of methods for the quantification of 25OH-D by using the human-based samples would reduce the inter-method variability. The best way for laboratories to demonstrate the accuracy of their results is by participating in the external quality assessment scheme. Standardization of the assays is also required to provide clinicians with the accurate tools to diagnose hypovitaminosis. In addition, assay-specific decision limits are needed to define appropriate thresholds of treatment.

Coronary artery vitamin D receptor expression and plasma concentrations of 25-hydroxyvitamin D: their association with atherosclerosis.

The aim of this study was to analyze coronary artery vitamin D receptor (VDR) expression, the plasma concentrations of 25-hydroxyvitamin D3 (25OHD3), and their relationship with coronary artery atherosclerosis. Premenopausal cynomolgus monkeys were fed atherogenic diets containing the equivalent of 1,000 IU/day of vitamin D3. Protein was derived from casein-lactalbumin (C/L, n = 10), soy protein isolate (soy, n = 10), or a combination (n = 19). After 32 months of consuming the diets, each monkey underwent surgical menopause. After 32 postmenopausal months, coronary atherosclerosis was measured in the left circumflex (LCX) artery and left anterior descending (LAD) artery. VDR expression was determined for the LAD, and 25OHD3 concentrations were assessed. Both the cross-sectional area of atherosclerotic plaques (in square millimeters) and plaque thickness (in millimeters) in the LCX as well as the LAD arteries were analyzed in these monkeys. Those with higher plasma vitamin D3 concentrations and higher VDR were compared with those with higher plasma 25OHD3 concentrations and lower VDR. Significantly smaller plaque sizes were noted with higher plasma 25OHD3 concentrations and higher VDR. For the LCX artery, there was also a significantly lower plaque size (both plaque thickness and cross-sectional area) in those with higher quantities of VDR and lower 25OHD3 concentrations versus those with lower quantities of VDR and higher plasma concentrations of 25OHD3 (P = 0.009 and P = 0.040, respectively). Cynomolgus monkeys with higher quantities of VDR have significantly less atherosclerosis than do those with lower quantities of VDR and higher plasma 25OHD3 concentrations. If these findings translate to human beings, it might explain why some individuals with higher plasma concentrations of 25OHD3 have more coronary artery atherosclerosis.

Expression of vitamin D-metabolizing enzymes in human adipose tissue—the effect of obesity and diet-induced weight loss

Low vitamin D (VD) levels are common in obesity. We hypothesized that this may be due to metabolism of VD in adipose tissue (AT). Thus, we studied (1) whether the VD-metabolizing enzymes were expressed differently in AT of lean and obese individuals and in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and (2) whether their expression was influenced by weight loss. Samples of SAT and VAT were analyzed for expression of the vitamin-D-25-hydroxylases CYP2R1, CYP2J2, CYP27A1 and CYP3A4, the 25-vitamin-D-1α-hydroxylase CYP27B1, the catabolic vitamin-D-24-hydroxylase CYP24A1, and the vitamin D receptor, using reverse transcriptase-PCR. Moreover, plasma 25-hydroxy-vitamin D (25OHD) level was measured and related to the expression of these enzymes. Samples of SAT and VAT from 20 lean women and 20 obese women, and samples of SAT from 17 obese subjects before and after a 10% weight loss were analyzed. A plasma 25OHD level <50 nmol l(-1) was highly prevalent in both lean (45%) and obese (90%) women (P<0.01). Plasma 25OHD increased by 27% after weight loss in the obese individuals (P<0.05). Expression levels of the 25-hydroxylase CYP2J2 and the 1α-hydroxylase CYP27B1 were decreased by 71% (P<0.0001) and 49% (P<0.05), respectively, in SAT of the obese. CYP24A1 did not differ between lean and obese women, but the expression was increased by 79% (P<0.05) after weight loss. Obesity is characterized by a decreased expression of the 25-hydroxylase CYP2J2 and the 1α-hydroxylase CYP27B1 in SAT, whereas the catabolic CYP24A1 does not differ between lean and obese women. However, the expression of CYP24A1 is increased after weight loss. Accordingly, AT has the capacity to metabolize VD locally, and this can be dynamically altered during obesity and weight loss.

Response to an Adequate Dietary Intake of Vitamin D3 Modulates the Effect of Estrogen Therapy on Bone Density

This study analyzed associations between plasma vitamin D(3) (25OHD(3)) and bone mineral density (BMD) and whether the effects of conjugated equine estrogens (CEE) on BMD are modulated by 25OHD(3). Fifty cynomolgus monkeys were fed a diet containing 25OHD(3) (providing a woman's equivalent of 1000 IU/day of 25OHD3). The monkeys underwent bilateral oophorectomy and were randomized to either CEE (equivalent of 0.45 mg/day) (n=25) or placebo (n=25) and continued receiving the same diet. 25OHD(3) and BMD were measured at randomization and after 6 months. BMD also was measured after 20 months (equivalent to 6 human years). Associations between 25OHD(3) and BMD were subsequently analyzed. Baseline 25OHD(3) plasma concentrations varied from 26 to 95 ng/mL (mean±standard deviation [SD] 54 ± 15 ng/mL). Higher plasma concentrations of 25OHD(3) were associated with a significantly increased BMD. Monkeys on both CEE and placebo had increased BMD over 20 months; however, the increase was not significantly different (0.034 g/cm(2) vs. 0.020 g/cm(2), respectively; p=0.064). The 20-month BMD increased significantly with CEE treatment in those with higher vs. lower 25OHD(3) concentrations (p=0.027). The percent change in BMD over 20 months also increased significantly with CEE treatment in those with higher vs. lower 25OHD(3) concentrations (p=0.018). A higher 25OHD(3) concentration had no significant effect on BMD in those receiving placebo. Monkeys fed a diet containing 1000 IU/day equivalent of 25OHD(3) have a wide range of plasma 25OHD(3) concentrations. Those receiving CEE with higher 25OHD(3) concentrations had higher BMDs, suggesting 25OHD(3) and CEE have synergistic effects on BMD.