Twice single doses of 100,000 IU of vitamin D in winter is adequate and safe for prevention of vitamin D deficiency in healthy children from Ushuaia, Tierra Del Fuego, Argentina

In order to improve vitamin D status of children from Ushuaia (55°S), at the South of Argentina, double supplementation with 100.000 IU of vitamin D was administered at the beginning of winter (March 2004), and 3 months later during winter (June 2004). In 2004, serum 25-hydroxyvitamin D (25OHD) was measured before the first supplementation, a month after, and 3 months after receiving the second supplementation (March, April and September). We studied 18 healthy children from Ushuaia, age (mean ± S.D.) 7.3 ± 4.4 years old (range 1.2–14.6), seven girls and 11 boys. Before treatment, serum 25OHD was 29.3 ± 5.9 ng/ml. It increased significantly 1 month after the first supplementation (April): 35.3 ± 4.4 ng/ml (p < 0.001), and decreased significantly 3 months after the second supplementation: 22.4 ± 4.6 ng/ml (September (p < 0.001). No child was neither deficient (<10 ng/ml) nor insufficient (10–15 ng/ml) of vitamin D. On April, a month after the first supplementation, no children had vitamin D intoxication levels (>50 ng/ml). These results disclosed that to prevent vitamin D deficiency for children at zones of risk at the south of our country, double supplementation of 100,000 IU of vitamin D during autumn and winter, would be adequate and safe.     

Vitamin D is a major determinant of bone mineral density at school age

Background

Vitamin D insufficiency in children may have long-term skeletal consequences as vitamin D affects calcium absorption, bone mineralization and bone mass attainment.

Methodology/Principal Findings

This school-based study investigated vitamin D status and its association with vitamin D intake and bone health in 195 Finnish children and adolescents (age range 7–19 years). Clinical characteristics, physical activity and dietary vitamin D intake were evaluated. Blood and urine samples were collected for serum 25-hydroxyvitamin D (25-OHD) and other parameters of calcium homeostasis. Bone mineral density (BMD) and body composition were measured with dual-energy X-ray absorptiometry (DXA). Altogether 71% of the subjects were vitamin D insufficient (25-OHD <50 nmol/L). The median 25-OHD was 41 nmol/L for girls and 45 nmol/L for boys, and the respective median vitamin D intakes 9.1 µg/day and 10 µg/day. In regression analysis, after adjusting for relevant factors, 25-OHD concentration explained 5.6% of the variance in lumbar BMD; 25-OHD and exercise together explained 7.6% of the variance in total hip BMD and 17% of the variance in whole body BMD. S-25-OHD was an independent determinant of lumbar spine and whole body BMD and in magnitude surpassed the effects of physical activity.

Conclusions/Significance

Vitamin D insufficiency was common even when vitamin D intake exceeded the recommended daily intake. Vitamin D status was a key determinant of BMD. The findings suggest urgent need to increase vitamin D intake to optimize bone health in children.     

ED-71, a new active vitamin D3, increases bone mineral density regardless of serum 25(OH)D levels in osteoporotic subjects

A previous randomized placebo-controlled double-blinded clinical trial revealed that treatment of osteoporotic subjects supplemented with 200 or 400 IU/day vitamin D3 with 0.75 μg/day ED-71 for 12 months increased lumbar and hip bone mineral density (BMD) by 3.4 and 1.5%, respectively, compared to placebo group (JCE&M 90:5031,2005). These effects on BMD were stronger than any previous results using 1(OH)D3 or 1,25(OH)2D3. However, there still was a concern that the effect of ED-71 could be observed because serum 25(OH)D in many of these subjects were below its optimal level. In order to address this issue, we performed post hoc analysis to compare the effect of ED-71 on lumbar and hip BMD between subjects with upper (>29 ng/mL) and lower tertiles (<25 ng/mL) of serum 25(OH)D. Lumbar BMD after 12-month treatment with 0.5, 0.75 and 1.0 μg/day ED-71 increased similarly in both lower and upper tertile groups of serum 25(OH)D. In addition, hip BMD also showed a tendency to increase when 0.75 and 1.0 μg/day ED-71 groups were combined together in both upper and lower serum 25(OH)D tertile groups, although the increase was not statistically significant. These results demonstrate that the effect of ED-71 on bone is independent of supplementary effect for nutritional vitamin D insufficiency, and suggest that ED-71 may exert its effect as a unique VDR ligand with stronger effect on bone compared to the natural ligand, 1,25(OH)2D3.     

The Vitamin D requirement in health and disease

Advances in Vitamin D nutritional physiology since publication of the DRIs in 1997 are briefly summarized. Available data indicate that (1) Vitamin D's canonical function, optimizing intestinal calcium absorption, is fully expressed at serum 25-hydroxyvitamin D (25OHD) concentration of approximately 80nmol/L; (2) elevated parathyroid activity, typical of aging populations, is minimized at the same 25OHD value and (3) osteoporotic fractures are reduced when serum 25OHD is raised to near 80nmol/L. Depending upon starting value, achieving 25OHD concentrations of 80 or higher may require a daily oral intake of 2200IU (55microg) or more in addition to prevailing cutaneous inputs. The tolerable upper intake level (TUIL), currently set at 2000IU (50microg)/day, is too low to permit optimization of Vitamin D status in the general population. Actual toxicity is not seen below serum 25OHD values of 250nmol/L, a value that would be produced only at continuing oral intakes in excess of 10,000IU (250microg)/day.     

Circulating vitamin D3 and 25-hydroxyvitamin D in humans: An important tool to define adequate nutritional vitamin D status

Circulating 25-hydroxyvitamin D [25(OH)D] is generally considered the means by which we define nutritional vitamin D status. There is much debate, however, with respect to what a healthy minimum level of circulation 25(OH)D should be. Recent data using various biomarkers such as intact parathyroid hormone (PTH), intestinal calcium absorption, and skeletal density measurements suggest this minimum level to be 80 nmol (32 ng/mL). Surprisingly, the relationship between circulating vitamin D₃ and its metabolic product—25(OH)D₃ has not been studied. We investigated this relationship in two separate populations: the first, individuals from Hawaii who received significant sun exposure; the second, subjects from a lactation study who received up to 6400 IU vitamin D₃/day for 6 months.

Results (1) the relationship between circulating vitamin D₃ and 25(OH)D in both groups was not linear, but appeared saturable and controlled; (2) optimal nutritional vitamin D status appeared to occur when molar ratios of circulating vitamin D₃ and 25(OH)D exceeded 0.3; at this point, the V_max of the 25-hydroxylase appeared to be achieved. This was achieved when circulating 25(OH)D exceeded 100 nmol.

We hypothesize that as humans live today, the 25-hydroxylase operates well below its V_max because of chronic substrate deficiency, namely vitamin D₃. When humans are sun (or dietary) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate. Thus, the relationship between circulating vitamin D and 25(OH)D may represent what “normal” vitamin D status should be.     

Seasonality of UV-radiation and vitamin D status at 69 degrees north.

The main purpose with this study was to assess the seasonal variation in measured UV-radiation and its impact on vitamin D status throughout one year in subjects living at high latitude. Blood samples drawn from 60 volunteers (44 women, 16 men) living at Andenes (69 degrees N), Norway, were collected throughout one year, at two-month intervals. The blood samples were analysed for 25-hydroxy vitamin D [25(OH)D]. Data on dietary intakes of vitamin D, time spent in daylight, use of sun beds and sun seeking holidays were collected by using questionnaires. The ambient vitamin D effective UV-radiation was measured at a site near by Andenes, and the number of hours spent outdoors with sufficient radiation for cutaneous vitamin D production (UV-hours) was estimated for each day. The mean 25(OH)D values were significantly higher at the end of the summer and in December, 2004 and varied from 42.0 nmol L(-1) in October, 2004 and April, 2005 to around 47 nmol L(-1) in December, 2004 and September, 2005. For the whole group, a positive relationship between UV-hours and 25(OH)D was found at UV-hours>or=3.5. However, for subjects with lower 25(OH)D levels i.e. at least one blood measurement with 25(OH)D<37.5 nmol L(-1), the positive relationship were found at around 1.5 UV-hours and more, whereas for the group of subjects that had all their vitamin D values above 37.5 nmol L(-1), positive relationship was found at UV-hours>or=4.0, when adjusting for vitamin D intake, sun bed use and sun seeking holidays. The generally high dietary intakes of vitamin D, especially in winter, mask largely the effect of seasonal variation in UV-exposure, causing an atypical seasonal variation in vitamin D status. The UV-hour variable significantly predicted 25(OH)D levels in blood when adjusted for intakes and artificial UV-radiation exposure and sun holidays abroad.     

Agreement of blood spot card measurements of vitamin D levels with serum, whole blood specimen types and a dietary recall instrument

Background

The ability to measure 25-hydroxyvitamin D (25OHD) levels from blood spot cards can simplify sample collection versus samples obtained by venipuncture, particularly in populations in whom it is difficult to draw blood. We sought to validate the use of blood spot samples for the measurement of 25OHD compared to serum or whole blood samples and correlate the measured levels with intake estimated from dietary recall.

Methods

Utilizing 109 biological mothers of infants enrolled in the Tennessee Children''s Respiratory Initiative cohort, we measured 25OHD levels through highly selective liquid chromatography–tandem mass spectrometry on samples from blood spot cards, serum, and whole blood collected at enrollment. Dietary questionnaires (n = 65) were used to assess 25OHD intake by dietary recall. Sample collection measures were assessed for agreement and 25OHD levels for association with dietary 25OHD intake.

Results

The mean absolute differences (95%CI) in 25OHD levels measured between whole blood and blood spot (n = 50 pairs) or serum and blood spot (n = 20) were 3.2 (95%CI:1.6, 4.8) ng/ml and 1.5 (95%CI:−0.5,3.4) ng/mL. Intake by dietary recall was marginally associated with 25OHD levels after adjustment for current smoking and race in linear regression.

Discussion

25OHD levels determined by mass spectrometry from blood spot cards, serum and whole blood show relatively good agreement, although 25OHD levels are slightly lower when measured by blood spot cards. Blood spot samples are a less invasive means of obtaining 25OHD measurements, particularly in large population-based samples, or among children when venipuncture may decrease study participation.     

Vitamin D Intakes of Ontario Children

A study to determine approximate intakes of vitamin D and sources contributing this nutrient was conducted among 1000 children, aged one week to 5½ years, in two Ontario Health Units in 1963 and 1964. Over 70% of the children obtained daily intakes above the recommended level, 400 I.U. Supplements provided about 60% of the total intake in children aged 7 months to 66 months who consumed 1000-1800 I.U. or more. In the intake range 1-399 I.U., fortified foods supplied 87% of the vitamin D to this age group. Influences of subsequent Food and Drug Directorate regulations, (a) withdrawing vitamin D from four foods used during the survey and (b) the effect of permissive vitamin D fortification of fluid milk products, were examined theoretically, by age and intake level. Programs directed to planning net intakes of 400 I.U. vitamin D, encouraging the use of fortified milk and discouraging the use of vitamin D supplements are described.     

Dietary recommendations to meet both endocrine and autocrine needs of Vitamin D

In the most recent revision of the dietary recommendations for Americans and Canadians in 1997, a recommended intake for Vitamin D was set in the absence of an estimation of mean requirements. There are now new data to estimate average requirements; however, there must be consideration of factors affecting need in populations and of total body tissue needs including the prevention and treatment of cancer. A recent study provides dietary dose-response data in the absence of sun exposure, and a mean requirement of 12.5microg (500IU) was found for Caucasian men. A seasonal build up (summer) and waning (winter) of Vitamin D stores implies that the requirement of Vitamin D in complete absence of yearly summertime sun exposure would approach levels of intake that mimic Vitamin D gained from sun exposure. High prevalence of Vitamin D insufficiency and the re-emergence of rickets have been observed worldwide. For many countries without mandatory staple food fortification, Vitamin D intake is often too low to sustain healthy circulating levels of 25 hydroxyvitamin D. Even in some countries that require (mandatory) or allow fortification (optional), Vitamin D intakes are low in some groups due to their unique dietary patterns, such as low milk consumption, vegetarian diet, limited or no use of dietary supplements, or changes away from traditional food consumption. Supplement use can significantly increase Vitamin D intakes across all age and gender groups but the benefit is primarily gained in persons whose intakes are close to adequate. African American men and women have greater prevalence of Vitamin D insufficiency, which may be a factor in their susceptibility to certain cancers. New recommendations for Vitamin D should be made for the otherwise healthy populations in greatest need of dietary Vitamin D due to lack of adequate sun exposure.     

Independent Association of Circulating Vitamin D Metabolites with Anemia Risk in Patients Scheduled for Cardiac Surgery

Background

Preoperative anemia is considered an independent risk factor of poor clinical outcome in cardiac surgical patients. Low vitamin D status may increase anemia risk.

Methods

We investigated 3,615 consecutive patients scheduled for cardiac surgery to determine the association between preoperative anemia (hemoglobin [Hb] <12.5 g/dL) and circulating levels of the vitamin D metabolites 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25[OH]₂D).

Results

Of the study cohort, 27.8 % met the criteria for anemia. In patients with deficient 25OHD levels (<30 nmol/l) mean Hb concentrations were 0.5 g/dL lower than in patients with adequate 25OHD levels (50.0–125 nmol/l; P<0.001). Regarding 1,25(OH)₂D, mean Hb concentrations were 1.2 g/dL lower in the lowest 1,25(OH)₂D category (<40 pmol/l) than in the highest 1,25(OH)₂D category (>70 pmol/l; P<0.001). In multivariable–adjusted logistic regression analyses, the odds ratios for anemia of the lowest categories of 25OHD and 1,25(OH)₂D were 1.48 (95%CI:1.19-1.83) and 2.35 (95%CI:1.86-2.97), compared with patients who had adequate 25OHD levels and 1,25(OH)₂D values in the highest category, respectively. Anemia risk was greatest in patients with dual deficiency of 25OHD and 1,25(OH)₂D (multivariable-adjusted OR = 3.60 (95%CI:2.40-5.40). Prevalence of deficient 25OHD levels was highest in anemia of nutrient deficiency, whereas low 1,25(OH)₂D levels were most frequent in anemia of chronic kidney disease.

Conclusion

This cross-sectional study demonstrates an independent inverse association between vitamin D status and anemia risk. If confirmed in clinical trials, preoperative administration of vitamin D or activated vitamin D (in case of chronic kidney disease) would be a promising strategy to prevent anemia in patients scheduled for cardiac surgery.     

Serum 25‐Hydroxyvitamin D Concentration,Life Factors and Obesity in Mexican Children

Although current evidence emphasizes a high prevalence of vitamin D deficiency and an inverse association between serum 25‐hydroxyvitamin D (25‐OHD) concentration and obesity, no studies have been conducted in Mexican children. The objective was to determine the prevalence of vitamin D deficiency and its association with obesity and lifestyle factors in a sample of school‐aged Mexican children. A cross‐sectional study of 99 obese and 99 nonobese 6–12 year‐old children, skin phototypes III–V, from six public schools was conducted during summer at latitude 25°40′, in northeastern Mexico. Anthropometric measurements were determined. Serum 25‐OHD was measured by immunoluminometric direct assay. Consumption of foods rich in vitamin D, sunscreen use and vitamin consumption were assessed through applied questionnaires. 62.1% of the subjects had insufficiency of 25‐OHD (21–29 ng/ml) and 20.2% had deficiency (<20 ng/ml). Obese subjects (BMI ≥95th percentile for age and gender) had significantly lower concentration of 25‐OHD than nonobese. Predictors of 25‐OHD concentration were, in order of significance: percentage of body fat, BMI, triceps skin fold, and waist circumference (WC). A significantly higher rate of 25‐OHD deficiency was observed in children with inadequate milk/yoghurt consumption, but no difference was found for other foods, physical activity (PA) or screen‐time. In a multivariate model, being obese was significantly associated with the risk of 25‐OHD deficiency, after adjustment for PA, screen‐time, skin phototype, ingestion of milk/yoghurt, fish, cheese, and carbonated beverages. A high prevalence of vitamin D deficiency and an inverse association between serum 25‐OHD concentration and obesity was found.     

Vitamin D status and nutrition in Europe and Asia

Vitamin D status is highly different in various countries of Europe, the Middle East and Asia. For this review, vitamin D deficiency is defined as serum 25-hydroxyvitamin D (25(OH)D) <25 nmol/l. Within European countries, serum 25(OH)D is <25 nmol/l in 2–30% of adults, increasing in the elderly and institutionalized to more than 80% in some studies. A north-south gradient was observed for serum 25(OH)D in the Euronut and MORE studies with higher levels in Scandinavia and lower levels in Italy and Spain and some Eastern European countries. This points to other determinants than sunshine, e.g. nutrition, food fortification and supplement use. Mean vitamin D intake in Scandinavia is 200–400 IU/d, twice that in other European countries. Very low serum 25(OH)D levels have been reported in the Middle East, e.g. Turkey, Lebanon, Jordan and Iran. In these countries serum 25(OH)D was lower in women than in men and associated with clothing habits. In a Lebanese survey, vitamin D deficiency was observed in the majority and occurred mainly in veiled women. In India, vitamin D deficiency was observed in more than 30%, vitamin D status being poor in school children, pregnant women and large cities. Vitamin D status was much better in Malaysia and Singapore, but lower serum 25(OH)D was observed in Japan and China. Rickets and osteomalacia appear quite common in India, but precise data are lacking. Immigrants in Europe from the Middle East and Asia carry a high risk for vitamin D deficiency, pregnant women being especially at risk. Comparison of vitamin D status between countries is hampered by interlaboratory variation of serum 25(OH)D measurement. In addition, there is a need of population-based data. In conclusion, vitamin D deficiency is common in Southern Europe, the Middle East, India, China and Japan. It is less common in Northern Europe and Southeast Asia. Risk groups are young children, the elderly, pregnant women and non-western immigrants in Europe. Important determinants are skin type, sex, clothing, nutrition, food fortification, supplement use, BMI and degree of urbanization.     

Pretreatment serum concentrations of 25-hydroxyvitamin D and breast cancer prognostic characteristics: a case-control and a case-series study

Background

Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity.

Methods and Findings

In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08–0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22–0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses.

Conclusion

In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women.     

Vitamin D binding protein and monocyte response to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D: analysis by mathematical modeling

Vitamin D binding protein (DBP) plays a key role in the bioavailability of active 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and its precursor 25-hydroxyvitamin D (25OHD), but accurate analysis of DBP-bound and free 25OHD and 1,25(OH)(2)D is difficult. To address this, two new mathematical models were developed to estimate: 1) serum levels of free 25OHD/1,25(OH)(2)D based on DBP concentration and genotype; 2) the impact of DBP on the biological activity of 25OHD/1,25(OH)(2)D in vivo. The initial extracellular steady state (eSS) model predicted that 50 nM 25OHD and 100 pM 1,25(OH)(2)D), <0.1% 25OHD and <1.5% 1,25(OH)(2)D are 'free' in vivo. However, for any given concentration of total 25OHD, levels of free 25OHD are higher for low affinity versus high affinity forms of DBP. The eSS model was then combined with an intracellular (iSS) model that incorporated conversion of 25OHD to 1,25(OH)(2)D via the enzyme CYP27B1, as well as binding of 1,25(OH)(2)D to the vitamin D receptor (VDR). The iSS model was optimized to 25OHD/1,25(OH)(2)D-mediated in vitro dose-responsive induction of the vitamin D target gene cathelicidin (CAMP) in human monocytes. The iSS model was then used to predict vitamin D activity in vivo (100% serum). The predicted induction of CAMP in vivo was minimal at basal settings but increased with enhanced expression of VDR (5-fold) and CYP27B1 (10-fold). Consistent with the eSS model, the iSS model predicted stronger responses to 25OHD for low affinity forms of DBP. Finally, the iSS model was used to compare the efficiency of endogenously synthesized versus exogenously added 1,25(OH)(2)D. Data strongly support the endogenous model as the most viable mode for CAMP induction by vitamin D in vivo. These novel mathematical models underline the importance of DBP as a determinant of vitamin D 'status' in vivo, with future implications for clinical studies of vitamin D status and supplementation.     

Interactions between Serum Vitamin D Levels and Vitamin D Receptor Gene FokI Polymorphisms for Renal Function in Patients with Type 2 Diabetes

Background

We aimed to examine associations among serum 25-hydroxyvitamin D (25OHD) levels, 1,25-dihyroxyvitamin D (1,25OHD) levels, vitamin D receptor (VDR) polymorphisms, and renal function based on estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.

Methods

In a cross-sectional study of 410 patients, chronic kidney disease (CKD) stage assessed by eGFR was compared with 25OHD, 1,25OHD, and VDR FokI (rs10735810) polymorphisms by an ordered logistic regression model adjusted for the following confounders: disease duration, calendar month, use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers or statins, and serum calcium, phosphate, and intact parathyroid hormone levels.

Results

1,25OHD levels, rather than 25OHD levels, showed seasonal oscillations; peak levels were seen from May to October and the lowest levels were seen from December to February. These findings were evident in patients with CKD stage 3∼5 but not stage 1∼2. eGFR was in direct proportion to both 25OHD and 1,25OHD levels (P<0.0001), but it had stronger linearity with 1,25OHD (r = 0.73) than 25OHD (r = 0.22) levels. Using multivariate analysis, 1,25OHD levels (P<0.001), but not 25OHD levels, were negatively associated with CKD stage. Although FokI polymorphisms by themselves showed no significant associations with CKD stage, a significant interaction between 1,25OHD and FokITT was observed (P = 0.008). The positive association between 1,25OHD and eGFR was steeper in FokICT and CC polymorphisms (r = 0.74) than FokITT polymorphisms (r = 0.65).

Conclusions

These results suggest that higher 1,25OHD levels may be associated with better CKD stages in patients with type 2 diabetes and that this association was modified by FokI polymorphisms.     

Effects of diet and exercise on plasma vitamin D (25(OH)D) levels in Vietnamese immigrant elderly in Sydney, Australia

Vitamin D deficiency may be associated with osteoporosis and fractures in the elderly. In Australia where there is a sizeable Vietnamese population, research has not yet clarified the roles of diet, exercise and sun exposure in determining vitamin D status. Plasma samples for 25-hydroxy-vitamin D (25(OH)D); dietary intake of vitamin D and calcium; muscle strength and sun exposure were measured and weekly dairy intake, exercise levels and smoking habits were surveyed in free-living elderly of Vietnamese and Australian/British origin. There was marginal vitamin D deficiency (<37 nmol/L 25(OH)D) in 63% of Vietnamese but only in 37% of Australian/British born. Low dairy intake and no vigorous exercise were best predictors of vitamin D deficiency in Vietnamese, taking into account age, gender, dietary intake and sun exposure. Since these migrant elderly may not get adequate sun exposure due to either clothing customs or cultural norms that encourage fair (untanned) skin, it is important to encourage increased exercise and dairy intake.     

A simple method for the isolation of vitamin D metabolites from plasma extracts

A simple method has been developed using 'SEP-PAK' disposable silica cartridges to separate the major endogenous vitamin D metabolites, namely vitamin D3, 25-hydroxy vitamin D3 (25OHD3), 1,25 dihydroxy vitamin D3 (1.25 (OH)2D3) and 24,25 dihydroxyvitamin D3 (24,25 (OH) 2D3). After extraction of plasma in isopropanol-toluene (25:75) the dried extract is reconstituted in hexane; this is applied to a SEP-PAK column, and stepwise elution carried out under gravity with 0.1 divided by isopropanol in hexane (neutral lipids), 1% isopropanol in hexane (D3), 3 divided by isopropanol in hexane (25OHD3), 3.125 divided by ethanol in dichloromethane (24,25 (OH) 2D3) and 50 divided ethanol in toluene (1, 25(OH) 2D3). Complete separation of these D3 metabolites is achieved by this process and up to 40 samples can be handled at one time.If combined with a suitable ligand binding assay, the system appears to be suitable for preparation of samples prior to the routine assay of vitamin D metabolites.     

1alpha,25-Dihydroxyvitamin D hydroxylase in adipocytes

High vitamin D intake is associated with reduced insulin resistance. Expression of extra-renal 1alpha,25-dihydroxyvitamin D hydroxylase (1alpha-hydroxylase) has been reported in several tissues and contributes to local synthesis of 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D) from the substrate 25-hydroxyvitamin D (25OHD). Expression and dietary regulation of 1alpha-hydroxylase in tissues associated with energy metabolism, including adipose tissue, has not been assessed. Male Wistar rats were fed a high calcium (1.5%) and high vitamin D (10,000IU/kg) or a low calcium (0.25%), low vitamin D (400IU/kg) with either a high fat (40% energy) or high sucrose (66% energy) dietary background for 14 weeks. Expression of 1alpha-hydroxylase, assessed by real time PCR, was detected in adipose tissue and did not differ with dietary level of calcium and vitamin D. 1alpha-Hydroxylase mRNA was also detected in 3T3-L1 preadipocytes and 25OHD treatment at 10nM levels induced 1,25(OH)(2)D responsive gene, CYP24, and this response was reduced in the presence of the p450 inhibitor, ketoconazole. In addition, (3)H 25OHD was converted to (3)H 1,25(OH)(2)D in intact 3T3-L1 preadipocytes. Cumulatively, these results demonstrate that 1alpha-hydroxylase is expressed in adipose tissue and is functional in cultured adipocytes. Thus, the capacity for local production may play a role in regulating adipocyte growth and metabolism.     

Pre-diagnostic plasma 25-hydroxyvitamin D levels and risk of non-melanoma skin cancer in women

Background

Recent reports have shown that vitamin D status was inversely associated with the risk of various cancers. However, few studies examined the association between vitamin D levels and risk of skin cancer.

Methods

We prospectively evaluated the association between baseline plasma 25(OH)D levels and the risk of incident squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) among 4,641 women from the Nurses’ Health Study (NHS) and the NHS II with 510 incident BCC cases and 75 incident SCC cases. We used multivariate logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Plasma 25(OH)D levels were positively associated with risk of BCC after adjusting for age at blood draw, season of blood draw, lab batch, hair color, burning tendency, the number of sunburns, and ultra-violet B flux of residence at blood collection. Women in the highest quartile of 25(OH)D had more than 2-fold increased risk of BCC compared with women in the lowest quartile (OR = 2.07, 95% CI = 1.52–2.80, P for trend <0.0001). We also found a significantly positive association between plasma 25(OH)D levels and SCC risk after adjusting for the same covariates (OR, highest vs. lowest quartile  = 3.77, 95% CI = 1.70–8.36, P for trend  = 0.0002).

Conclusion

In this prospective study of women, plasma vitamin D levels were positively associated with non-melanoma skin cancer risk. Considering that most circulating vitamin D is due to sun exposure, the positive association between plasma vitamin D and non-melanoma skin cancer is confounded by sun exposure. Our data suggest that one-time measurement of plasma vitamin D levels may reasonably reflect long-term sun exposure and predict the risk of non-melanoma skin cancer.     

Intake of vitamin D and risk of breast cancer--a meta-analysis

Vitamin D insufficiency has been shown to be associated with a number of conditions including diabetes, multiple sclerosis and the overall risk of cancer. We aimed at studying the association between vitamin D intake and risk of breast cancer in a meta-analysis. We searched Pubmed, Embase, and Web of Science using the MESH terms "vitamin D" and "breast cancer". A total of 1731 studies were identified, but only 6 studies contained original data on the association between intake of vitamin D and risk of breast cancer. Overall there was no association between amount of vitamin D and risk of breast cancer (RR=0.98, 95% CI: 0.93-1.03, test for heterogeneity p<0.01). However, most studies reported on very low intakes of vitamin D (typically in the range 100-400IU/day). Restricting the analyses to intakes >/=400IU/day yielded a more homogenous result with a trend towards less breast cancer with >/=400IU/day vs. the lowest intake (typically <50-150IU/day), RR=0.92, 95% CI: 0.87-0.97, p for heterogeneity 0.14. In conclusion there may be a trend towards fewer cases of breast cancer with higher intakes of vitamin D (>/=400IU/day). However, more research is needed, preferably in the form of randomized-controlled trials.