Vitamin D Status and Seasonal Variation among Danish Children and Adults: A Descriptive Study.

The aim of the present study was to describe vitamin D status and seasonal variation in the general Danish population. In this study, 3092 persons aged 2 to 69 years (2565 adults, 527 children) had blood drawn twice (spring and autumn) between 2012 and 2014. A sub-sample of participants had blood samples taken monthly over a year. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured by liquid chromatography mass spectrometry, and information on supplement use was assessed from questionnaires. Seasonal variations in 25(OH)D concentrations were evaluated graphically and descriptively, and status according to age, sex, and supplement use was described. It was found that 86% of both adults and children were vitamin D-sufficient in either spring and or/autumn; however, many had a spring concentration below 50 nmol/L. A wide range of 25(OH)D concentrations were found in spring and autumn, with very low and very high values in both seasons. Among adults, women in general had higher median 25(OH)D concentrations than men. Furthermore, vitamin D supplement use was substantial and affected the median concentrations markedly, more so during spring than autumn. Seasonal variation was thus found to be substantial, and bi-seasonal measurements are vital in order to capture the sizable fluctuations in vitamin D status in this Nordic population.

Sun Exposure Guidelines and Serum Vitamin D Status in Denmark: The StatusD Study.

Little is known on how vitamin D status is affected by adherence to UVB-limiting sun exposure guidelines. Our aim was to investigate the relationship between adherence to the Danish sun exposure guidelines and vitamin D status. In total, 3194 Danes (2625 adults, 569 children) were recruited among the general population, and more than 92% had blood samples taken both autumn and spring. Using linear regression, we associated serum vitamin D concentrations to questionnaire responses on: seeking shade, wearing a sunhat, wearing protective clothing or using sunscreen. The odds ratio (OR) of either low (<25 or 50 nmol/L) or adequate/high (≥50 nmol/L) vitamin D status was examined using logistic regression. For adults, those who always sought shade or wore protective clothing compared to those who did not had lower levels of vitamin D (autumn concentrations for shade: 7.2 nmol/L lower (-11.0--3.6 nmol/L); for protective clothing: 9.9 nmol/L lower (-13.6--6.2 nmol/L). Adherence to all four guidelines was also associated with lower vitamin D concentrations (autumn: 9.7 nmol/L lower (-14.3--5.1 nmol/L). Use of sunscreen was associated with adequate vitamin D status, as those who always sought shade compared to those who did not had an OR (95% CI) of 1.68 (1.25-2.35) of having ≥50 nmol/L during both spring and autumn. No associations were found with wearing a sunhat, and there were no clear associations for children. In conclusion, adherence to the sun exposure guidelines on shade and protective clothing was associated with lower vitamin D status among Danish adults, but not children.

Increased fracture risk in normocalcemic postmenopausal women with high parathyroid hormone levels: a 16-year follow-up study.

High PTH levels increase bone turnover and decrease bone mineral density (BMD). Low plasma 25-hydroxyvitamin D (25OHD) levels cause secondary hyperparathyroidism, but the relative contribution of low 25OHD and high PTH levels on risk of fracture is largely unknown. Within the cohort of women (n = 2,016) included in the Danish Osteoporosis Prevention Study (DOPS), we studied risk of fracture according to parathyroid status. Analyses were performed on effects of high PTH levels (i.e., in the upper tertile, ≥4.5 pmol/L) on risk of incident fractures at different 25OHD levels during 16 years of follow-up. Incident fractures were assessed using a nationwide hospital discharge register. In addition, effects of high PTH levels on BMD and vertebral fractures were assessed by DXA scans and spinal X-ray examination after 10 years of follow-up. High PTH levels were associated with a decreased body mass index, adjusted BMD, and an increased risk of any fracture (HR = 1.41, 95% CI 1.11-1.79) as well as an increased risk of osteoporotic fractures (HR = 1.59, 95% CI 1.20-2.10). Plasma 25OHD levels per se did not affect fracture risk, but high PTH levels were associated with an increased fracture risk only at 25OHD levels <50 nmol/L and 50-80 nmol/L. High PTH levels did not increase risk of fracture at 25OHD levels >80 nmol/L. In conclusion, PTH levels in the upper part or above the upper level of the reference interval increase risk of fracture in the presence of low vitamin D levels.

Vitamin D status assessed by a validated HPLC method: within and between variation in subjects supplemented with vitamin D3.

OBJECTIVE: The aim of this study was to develop and validate a high-pressure liquid chromatography (HPLC) method for assessing vitamin D status as 25-hydroxyvitamin D(2) (S-25OHD(2)) and 25-hydroxyvitamin D(3) (S-25OHD(3)) in serum. MATERIAL AND METHODS: We assessed the within- and between-subject variation of vitamin D status in serum samples from four different dietary intervention studies in which subjects (n = 92) were supplemented with different doses of vitamin D(3) (5-12 microg/day) and for different durations (4-20 months). RESULTS: The HPLC method was applicable for 4.0-200 nmol S-25OHD/L, while the within-day and between-days variations were 3.8 % and 5.7 %, respectively. There was a concentration-dependent difference between results obtained by a commercial radioimmunoassay and results from the HPLC method of -5 to 20 nmol 25OHD/L in the range 10-100 nmol 25OHD/L. The between-subject variation estimated in each of the four human intervention studies did not differ significantly (p = 0.55). Hence, the pooled standard deviation was 15.3 nmol 25OHD(3)/L. In the studies with 6-8 samplings during 7-20 months of supplementation, the within-subject variation was 3.9-7.2 nmol 25OHD(3)/L, while vitamin D status was in the range 47-120 nmol/L. CONCLUSIONS: The validated HPLC method was applied in samples from human intervention studies in which subjects were supplemented with vitamin D(3). The estimated standard deviation between and within subjects is useful in the forthcoming decision on setting limits for optimal vitamin D status.

Parathyroid response to vitamin D insufficiency: relations to bone, body composition and to lifestyle characteristics.

BACKGROUND: Vitamin D insufficiency is very common and is known to cause secondary hyperparathyroidism (SHPT). However, in some subjects the PTH response to low vitamin D levels is blunted, which has been termed functional hypoparathyroidism (FHPT). AIM: We compared indices of calcium homeostasis, bone metabolism and body composition in subjects with differential PTH responses to low vitamin D levels. DESIGN: Cross-sectional study. In 405 recent postmenopausal women with vitamin D insufficiency, we compared levels of bone turnover markers, bone mineral density (BMD), body composition, and body weight between subjects with SHPT and FHPT. RESULTS: Plasma 25-hydroxyvitamin D (P-25OHD) levels were slightly higher (P < 0.05) in SHPT compared with FHPT. SHPT was associated with higher levels of osteocalcin and bone-specific alkaline phosphatase, whereas whole body BMD and hip- and lumbar spine-BMD were significantly reduced. Subjects with SHPT had a 7% (P < 0.01) higher body weight and a 23% higher fat mass (P < 0.01) than subjects with FHPT, whereas lean tissue mass did not differ between groups. In SHPT, fat mass was increased by 14% (P < 0.001) at the upper and lower extremities and by 33% (P < 0.001) at the trunk. In a regression model, significant predictors of fat mass was P-PTH (r(p) = 0.248, P < 0.01) and P-osteocalcin (r(p) = -0.115, P = 0.02), with no effects of P-25OHD or P-creatinine levels. CONCLUSIONS: Effects of vitamin D insufficiency on bone is associated with the PTH responses. The increased body weight and fat mass in SHPT compared with FHPT may imply that PTH excess contributes to fat accumulation.

Effect of vitamin D supplementation on bone and vitamin D status among Pakistani immigrants in Denmark: a randomised double-blinded placebo-controlled intervention study.

Severe vitamin D deficiency is common among Muslim immigrants. The dose necessary to correct the deficiency and its consequence for bone health are not known for immigrants. The aim was to assess the effect of relatively low dosages of supplemental vitamin D on vitamin D and bone status in Pakistani immigrants. This 1-year-long randomised double-blinded placebo-controlled intervention with vitamin D3 (10 and 20 microg/d) included girls (10.1-14.7 years), women (18.1-52.7 years) and men (17.9-63.5 years) of Pakistani origin living in Denmark. The main endpoints were serum 25-hydroxyvitamin D (S-25OHD), parathyroid hormone, bone turnover markers and bone mass. The study showed that supplementation with 10 and 20 microg vitamin D3 per d increased S-25OHD concentrations similarly in vitamin D-deficient Pakistani women (4-fold), and that 10 microg increased S-25OHD concentrations 2-fold and 20 microg 3-fold in Pakistani men. S-25OHD concentrations increased at 6 months and were stable thereafter. Baseline S-25OHD concentrations tended to be lower in girls and women than in men; females achieved about 46 nmol/l and men 55 nmol/l after supplementation. Serum intact parathyroid hormone concentrations decreased at 6 months, but there was no significant effect of the intervention on bone turnover markers and dual-energy X-ray absorptiometry measurements of the whole body and lumbar spine.

The effect of a high-protein, high-sodium diet on calcium and bone metabolism in postmenopausal women and its interaction with vitamin D receptor genotype.

The influence of a high-Na, high-protein (calciuric) diet on Ca and bone metabolism was investigated in postmenopausal women (aged 50-67 years) who were stratified by vitamin D receptor (VDR) genotype. In a crossover trial, twenty-four women were randomly assigned to a diet high in protein (90 g/d) and Na (180 mmol/d) or a diet adequate in protein (70 g/d) and low in Na (65 mmol/d) for 4 weeks, followed by crossover to the alternative dietary regimen for a further 4 weeks. Dietary Ca intake was maintained at usual intakes (about 20 mmol (800 mg)/d). Urinary Na, K, Ca, N and type I collagen cross-linked N-telopeptide (NTx; a marker of bone resorption), plasma parathyroid hormone (PTH), serum 25-hydroxycholecalciferol (25(OH)D3), 1,25-dihydroxycholecalciferol (1,25(OH)2D3), osteocalcin and bone-specific alkaline phosphatase (B-Alkphase) were measured in 24 h urine samples and fasting blood samples collected at the end of each dietary period. The calciuric diet significantly (P<0.05) increased mean urinary Na, N, K, Ca and NTx (by 19 %) compared with the basal diet, but had no effect on circulating 25(OH)D3, 1,25(OH)2D3, PTH, osteocalcin or B-Alkphase in the total group (n 24). There were no differences in serum markers or urinary minerals between the basal and calciuric diet in either VDR genotype groups. While the calciuric diet significantly increased urinary NTx (by 25.6 %, P<0.01) in the f+ VDR group (n 10; carrying one or more (f) Fok I alleles), it had no effect in the f- VDR group (n 14; not carrying any Fok I alleles). It is concluded that the Na- and protein-induced urinary Ca loss is compensated for by increased bone resorption and that this response may be influenced by VDR genotype.

Food contents and biological activity of 25-hydroxyvitamin D: a vitamin D metabolite to be reckoned with?

Only a limited number of foods naturally contain vitamin D such as fish, meat and offal, and eggs, and milk and dairy products. However, all these foods in addition contain the metabolite 25-hydroxyvitamin D (25OHD). From the few systematic studies which have been performed the food contents of 25OHD in animal foods are usually low but vary. Contents are typically very low in milk and fish (<0.1 microg/100 g), somewhat higher in meat and offal (0.2-0.4 microg/100 g) and up to 1 microg/100 g in egg yolk. It has been demonstrated that 25OHD is absorbed better and faster from the diet than native vitamin D and has metabolic effects of its own in regulating cell growth and calcium metabolism. Thus, the biological activity of 25OHD is greater than that of native vitamin D. However, there is as yet no consensus on the conversion factor that should be used for 25OHD to calculate vitamin D activity. Depending on the testing system used the factor varies from 1.5 to 5. If food contents and the higher potency of 25OHD are not included in dietary intake surveys, true vitamin D intake will be underestimated.