The effect of high-dose vitamin D3 supplementation on bone mineral density in subjects with prediabetes.

The rationale of this study was to determine the effect of high-dose vitamin D3 supplementation on bone mineral density (BMD). Prediabetic males given vitamin D had significantly less reduction in BMD at the femoral neck compared to the controls. The clinical implications of our findings require further investigation. INTRODUCTION: Type 2 diabetes mellitus is associated with increased fracture risk, and recent studies show crosstalk between bone and glucose metabolism. Few studies have investigated the effect of vitamin D supplementation on the bone without additional calcium. In the present study, we aimed to determine whether a high dose of vitamin D3 could improve bone mass density (BMD) in prediabetic subjects. METHODS: The current study was conducted as a secondary research on a previously performed trial, in which 511 subjects with prediabetes were randomized to vitamin D3 (20,000 IU per week) versus placebo for 5 years. BMD was measured using dual-energy X-ray absorptiometry (DEXA). RESULTS: Two hundred and fifty-six subjects were randomized to vitamin D and 255 to placebo. Mean baseline serum 25-hydroxyvitamin D (25(OH)D) level was 60 nmol/L. Two hundred and two and 214 in the vitamin D and placebo groups, respectively, completed BMD measurements, whereas one in each group was excluded due to use of bisphosphonates. Males given vitamin D had significantly less reduction in BMD at the femoral neck measurement site compared to the controls (0.000 versus - 0.010 g/cm2, p = 0.008). No significant differences between intervention groups were seen at the total hip measurement site, regarding both males and females. CONCLUSIONS: Vitamin D3 supplementation alone may be beneficial in males with prediabetes, but confirmatory studies are needed.

Serum parathyroid hormone is associated with increased cortical porosity of the inner transitional zone at the proximal femur in postmenopausal women: the Tromsø Study.

Serum parathyroid hormone (PTH) was associated with increased bone turnover markers and cortical porosity of the inner transitional zone at the proximal femur. These results suggest that PTH through increased intracortical bone turnover leads to trabecularisation of inner cortical bone in postmenopausal women. INTRODUCTION: Vitamin D deficiency leads to secondary hyperparathyroidism and increased risk for fractures, whereas its association with cortical porosity is less clear. We tested (i) whether serum 25-hydroxyvitamin D (25(OH)D) and PTH were associated with cortical porosity and (ii) whether the associations of 25(OH)D) and PTH with fracture risk are dependent on cortical porosity. METHODS: This case-control study included 211 postmenopausal women, 54-94 years old, with prevalent fractures and 232 controls from the Tromsø Study. Serum 25(OH)D, PTH, and bone turnover markers (procollagen type I N-terminal propeptide [PINP] and C-terminal cross-linking telopeptide of type I collagen [CTX]) were measured. Femoral subtrochanteric cortical and trabecular parameters were quantified using computed tomography, and femoral neck areal bone mineral density (FN aBMD) was quantified using dual-energy X-ray absorptiometry. RESULTS: Compared with controls, fracture cases exhibited reduced serum 25(OH)D and increased PTH, PINP, and CTX, increased femoral subtrochanteric cortical porosity, and reduced cortical thickness and FN aBMD (all, p < 0.05). Serum 25(OH)D was not associated with cortical parameters (all, p > 0.10). PTH was associated with increased PINP, CTX, and cortical porosity of the inner transitional zone and reduced trabecular bone volume/tissue volume and FN aBMD (p ranging from 0.003 to 0.054). Decreasing 25(OH)D and increasing PTH were associated with increased odds for fractures, independent of age, height, weight, calcium supplementation, serum calcium, cortical porosity, and thickness. CONCLUSIONS: These data suggest that serum PTH, not 25(OH)D, is associated with increased intracortical bone turnover resulting in trabecularisation of the inner cortical bone; nevertheless, decreasing 25(OH)D) and increasing PTH are associated with fracture risk, independent of cortical porosity and thickness.

The association between childhood fractures and adolescence bone outcomes: a population-based study, the Tromsø Study, Fit Futures.

Childhood fracture may predict persistent skeletal fragility, but it may also reflect high physical activity which is beneficial to bone development. We observe a difference in the relationship between previous fracture and bone outcome across physical activity level and sex. Further elaboration on this variation is needed. PURPOSE: Childhood fracture may be an early marker of skeletal fragility, or increased levels of physical activity (PA), which are beneficial for bone mineral accrual. This study investigated the association between a previous history of childhood fracture and adolescent bone mineral outcomes by various PA levels. METHODS: We recruited 469 girls and 492 boys aged 15-18 years to this study. We assessed PA levels by questionnaire and measured areal bone mineral density (aBMD) and bone mineral content (BMC) using dual-energy X-ray absorptiometry (DXA) at arm, femoral neck (FN), total hip (TH), and total body (TB) and calculated bone mineral apparent density (BMAD, g/cm3). Fractures from birth to time of DXA measurements were retrospectively recorded. We analyzed differences among participants with and without fractures using independent sample t test. Multiple linear regression was used to examine the association between fractures and aBMD and BMC measurements according to adolescent PA. RESULTS: Girls with and without a previous history of fracture had similar BMC, aBMD, and BMAD at all sites. In multiple regression analyses stratified by physical activity intensity (PAi), there was a significant negative association between fracture and aBMD-TH and BMC-FN yet only in girls reporting low PAi. There was a significant negative association between forearm fractures, BMAD-FN, and BMAD-arm among vigorously active boys. CONCLUSION: Our findings indicate a negative association between childhood fractures and aBMD/BMC in adolescent girls reporting low PAi. In boys, such an association appears only in vigorously active participants with a history of forearm fractures.

The effect of high-dose vitamin D supplementation on muscular function and quality of life in postmenopausal women-A randomized controlled trial.

OBJECTIVE: Observational studies have suggested positive associations between serum 25-hydroxyvitamin D (25(OH)D) levels and muscular strength, balance and quality of life. Our aim was to examine whether high-dose vitamin D supplementation would improve these measures as compared to standard-dose vitamin D, as well as the possible muscular effects of single nucleotide polymorphisms (SNPs) in genes encoding vitamin D-related enzymes. DESIGN: A 12-month randomized, double-blind, controlled trial where the participants received daily elemental calcium (1000 mg) plus vitamin D3 (800 IU). In addition, the participants were randomized to receive either capsules with vitamin D3 (20 000 IU) or matching placebos to be taken twice a week. PATIENTS: A total of 297 postmenopausal women with osteopenia or osteoporosis. MEASUREMENTS: Muscle strength (handgrip and knee extensor strength), balance (tandem test) and quality of life (EQ-5D) were measured at baseline and after 12 months. The subjects were genotyped for SNPs related to vitamin D metabolism. RESULTS: Of the 297 included women, 275 completed the study. Mean serum 25(OH)D levels dramatically increased in the high-dose group (from 64.7 to 164.1 nmol/L; P<.01), while a more moderate increased was observed in the standard-dose group (from 64.1 to 81.8 nmol/L; P<.01). There was no significant difference between the groups in change in muscular strength, balance or quality of life over the intervention period. Polymorphisms in rs3829251 (located in the 7-dehydrocholesterol reductase gene) were associated with muscle strength and treatment effects. CONCLUSION: One-year treatment with high-dose vitamin D had no effect on muscular strength, balance or quality of life in postmenopausal women with osteopenia or osteoporosis as compared to standard dose. The association between rs3829251 and muscle strength needs confirmation in other populations.

Continued decline in hip fracture incidence in Norway: a NOREPOS study.

UNLABELLED: The previously reported decline in age-adjusted hip fracture rates in Norway during 1999-2008 continued after 2008. The annual number of hip fractures decreased in women and increased in men. INTRODUCTION: Norway has among the highest hip fracture incidence rates ever reported despite previously observed declining rates from 1999 through 2008. The aim of the present study was to investigate whether this downward trend continued through 2013, and to compare gender-specific trends in 5 year age-groups during three time periods: 1999-2003, 2004-2008, and 2009-2013. METHODS: All hip fractures (cervical, trochanteric, and sub-trochanteric) admitted to Norwegian hospitals were retrieved. Annual age-standardized incidence rates of hip fracture per 10,000 person-years by gender were calculated for the period 1999-2013. Time trends were tested by age-adjusted Poisson regression. RESULTS: From 1999 through 2013 there were 140,136 hip fractures in persons aged 50 years and above. Age-adjusted hip fracture incidence rates declined by 20.4 % (95 % CI: 18.6-20.1) in women and 10.8 % (95 % CI: 7.8-13.8) in men, corresponding to an average annual age-adjusted decline of 1.5 % in women and 0.8 % in men. Except for the oldest men, hip fracture rates declined in all age-groups 70 years and older. The average annual number of fractures decreased in women (-0.3 %) and increased in men (+1.1 %). CONCLUSIONS: During the past 15 years, hip fracture rates have declined in Norway. The forecasted growing number of older individuals might, however, cause an increase in the absolute number of fractures, with a substantial societal economic and public health burden.

A combination of low serum concentrations of vitamins K1 and D is associated with increased risk of hip fractures in elderly Norwegians: a NOREPOS study.

UNLABELLED: The present study investigated the risk of incident hip fractures according to serum concentrations of vitamin K1 and 25-hydroxyvitamin D in elderly Norwegians during long-term follow-up. The results showed that the combination of low concentrations of both vitamin D and K1 provides a significant risk factor for hip fractures. INTRODUCTION: This case-cohort study aims to investigate the associations between serum vitamin K1 and hip fracture and the possible effect of 25-hydroxyvitamin D (25(OH)D) on this association. METHODS: The source cohort was 21,774 men and women aged 65 to 79 years who attended Norwegian community-based health studies during 1994-2001. Hip fractures were identified through hospital registers during median follow-up of 8.2 years. Vitamins were determined in serum obtained at baseline in all hip fracture cases (n = 1090) and in a randomly selected subcohort (n = 1318). Cox proportional hazards regression with quartiles of serum vitamin K1 as explanatory variable was performed. Analyses were further performed with the following four groups as explanatory variable: I: vitamin K1 ≥ 0.76 and 25(OH)D ≥ 50 nmol/l, II: vitamin K1 ≥ 0.76 and 25(OH)D < 50 nmol/l, III: vitamin K1 < 0.76 and 25(OH)D ≥ 50 nmol/l, and IV: vitamin K1 < 0.76 and 25(OH)D < 50 nmol/l. RESULTS: Age- and sex-adjusted analyses revealed an inverse association between quartiles of vitamin K1 and the risk of hip fracture. Further, a 50 % higher risk of hip fracture was observed in subjects with both low vitamin K1 and 25(OH)D compared with subjects with high vitamin K1 and 25(OH)D (HR 1.50, 95 % CI 1.18-1.90). The association remained statistically significant after adjusting for body mass index, smoking, triglycerides, and serum α-tocopherol. No increased risk was observed in the groups low in one vitamin only. CONCLUSION: Combination of low concentrations of vitamin K1 and 25(OH)D is associated with increased risk of hip fractures.

Low serum concentrations of alpha-tocopherol are associated with increased risk of hip fracture. A NOREPOS study.

UNLABELLED: We investigated the risk of hip fracture according to circulating alpha-tocopherol, a plant-derived substance with antioxidant properties, in community-dwelling older Norwegians. We found a linear increasing risk of hip fracture with lower serum alpha-tocopherol concentrations, with a 51% higher risk in the lowest compared to the highest quartile. INTRODUCTION: Oxidative stress is a suggested contributing cause of osteoporosis and fractures. Vitamin E (α-tocopherol) has potent antioxidant properties in humans. The relationship between circulating α-tocopherol and fracture risk is not established. The aim of this study was to investigate the association between serum α-tocopherol concentrations and risk of hip fracture during up to 11 years of follow-up. METHODS: We performed a case-cohort analysis among 21,774 men and women aged 65-79 years who participated in four community-based health studies in Norway 1994-2001. Serum α-tocopherol concentrations at baseline were determined in 1,168 men and women who subsequently suffered hip fractures (median follow-up 8.2 years) and in a random sample (n = 1,434) from the same cohort. Cox proportional hazard regression adapted for gender-stratified case-cohort data was performed. RESULTS: Median (25, 75 percentile) serum α-tocopherol was 30.0 (22.6, 38.3) µmol/L, and it showed a linear inverse association with hip fracture: hazard ratio (HR) 1.11 (95% confidence interval (CI) 1.04-1.20) per 10-µmol/L decrease in serum α-tocopherol, adjusted for gender and study center. The lowest compared to the highest quartile conferred an HR of 1.51 (95% CI 1.17-1.95), adjusted for gender and study center. Adjustment for smoking, month of blood sample, BMI, education, physical inactivity, self-rated health, and serum 25-hydroxyvitamin D (25(OH)D) yielded similar results. Taking serum total cholesterol concentration into account attenuated the association somewhat: HR of hip fracture was 1.37 (95% CI 1.05-1.77) in first versus fourth quartile of serum α-tocopherol/total cholesterol ratio. CONCLUSIONS: Low serum concentrations of α-tocopherol were associated with increased risk of hip fracture in older Norwegians.

Supplementation with vitamin D does not increase serum testosterone levels in healthy males.

Cross-sectional studies indicate a positive relation between serum 25-hydroxyvitamin D [25(OH)D] and testosterone. It is not known if this relation is causal, which in theory could be in both directions. A cross-sectional population based study was designed with pooled data from 3 vitamin D randomized clinical trials (RCTs) performed in Tromsø with weight reduction, insulin sensitivity, and depression scores as endpoints, and one testosterone RCT in subjects with low serum testosterone (<11.0 nmol/l) and with body composition as endpoint. Serum 25(OH)D and androgens were measured in 893 males in the cross-sectional part, at baseline and after 6-12 months of supplementation with vitamin D 20 000 IU-40 000 IU per week vs. placebo in the vitamin D RCTs (n=282), and at baseline and after one year treatment with testosterone undecanoate 1 000 mg or placebo injections (at baseline and after 6, 16, 28, and 40 weeks) in the testosterone RCT (n=37). In the cross-sectional study, serum 25(OH)D was found to be a significant and positive predictor of serum testosterone. In the vitamin D RCTs, no significant effect on serum total or free testosterone levels was seen, and in the testosterone RCT no significant effect on serum 25(OH)D was seen. This was unchanged in sub-analyses in subjects with low serum 25(OH)D (or testosterone) levels. In conclusion, in subjects without significant vitamin D deficiency, there is no increase in serum testosterone after high dose vitamin D supplementation. Similarly, in subjects with moderately low serum testosterone levels, substitution with testosterone does not increase serum 25(OH)D.

The effect of high-dose vitamin D on bone mineral density and bone turnover markers in postmenopausal women with low bone mass--a randomized controlled 1-year trial.

UNLABELLED: Vitamin D is widely used in osteoporosis treatment, although the optimal dose is not known. This 1-year clinical study among 297 women aged 50-80 years old showed that a vitamin D(3) dose of 6,500 IU/day was not better than the standard dose of 800 IU/day in improving bone mineral density (BMD) in the hip and spine. INTRODUCTION: The purpose of this study was to determine whether a high dose of vitamin D(3) was better than the standard dose in improving BMD and reducing bone turnover in postmenopausal women with reduced bone mass. METHODS: The study was a 1-year randomized double-blind controlled trial comparing high-dose vitamin D(3) with the standard dose. Postmenopausal women (n = 297) with a BMD T-score ≤ -2.0 in either lumbar spine (L2-4) or total hip were included and randomized to 6,500 IU vitamin D(3)/day (20,000 IU twice per week + 800 IU/day) or 800 IU vitamin D(3)/day (placebo twice per week + 800 IU/day). Both groups were given 1,000 mg elemental calcium/day. The primary endpoint was a change in BMD in total hip and lumbar spine (L2-4). RESULTS: After 1 year, serum 25-hydroxyvitamin D (25(OH)D) increased [mean (SD)] from 71 (23) to 185 (34) nmol/l and from 71 (22) to 89 (17) nmol/l in the high- and standard-dose vitamin D groups, respectively. BMD at all measurement sites was unchanged or slightly improved with no significant differences between the groups. Although bone turnover was reduced in both groups, the more pronounced reduction in serum levels of the bone formation marker P1NP in the standard-dose group may indicate that this treatment was more efficient. Adverse events did not differ between the groups. CONCLUSIONS: One year treatment with 6,500 IU vitamin D(3)/day was not better than 800 IU/day regarding BMD in vitamin D-replete postmenopausal women with reduced bone mass and was less efficient in reducing bone turnover.

Staphylococcus aureus nasal carriage is associated with serum 25-hydroxyvitamin D levels, gender and smoking status. The Tromsø Staph and Skin Study.

Vitamin D induces the expression of antimicrobial peptides with activity against Staphylococcus aureus. Thus, we studied the association between serum 25-hydroxyvitamin D (25(OH)D) and S. aureus nasal colonization and carriage. Nasal swabs, blood samples and clinical data from 2,115 women and 1,674 men, aged 30-87 years, were collected in the Tromsø Staph and Skin Study 2007-08, as part of the population-based sixth Tromsø Study. Multivariate logistic regression analyses were stratified by recognized risk factors for S. aureus carriage: sex, age and smoking. In non-smoking men, we observed a 6.6% and 6.7% decrease in the probability of S. aureus colonization and carriage, respectively, by each 5 nmol/l increase in serum 25(OH)D concentration (P < 0.001 and P = 0.001), and serum 25(OH)D > 59 nmol/l and ≥75 nmol/l as thresholds for ~30% and ~50% reduction in S. aureus colonization and carriage. In non-smoking men aged 44-60 years, the odds ratio for S. aureus colonization was 0.44 (95% confidence interval, 0.28-0.69) in the top tertile of serum 25(OH)D versus the bottom tertile. In women and smokers there were no such associations. Our study supports that serum vitamin D is a determinant of S. aureus colonization and carriage.

Associations of serum 25-hydroxyvitamin D and subjective sleep measures in an arctic population: Insights from the population-based Tromsø Study.

Objective: To investigate the relation between serum 25-hydroxyvitamin D (s-25(OH)D) and subjective sleep measures in an Arctic population (69°N). Methods: Cross-sectional data was collected from 21,083 individuals (aged ≥40 years) participating in the population based Tromsø Study: Tromsø7 (2015-2016). The present study included 20,438 participants, after having excluded respondents missing data on s-25(OH)D (n = 161) and/or subjective sleep measures (including sleep duration, insomnia, and daytime sleepiness)(n = 490). Based on s-25(OH)D (assessed using LC-MS/MS), participants were grouped as deficient (<30 nmol/L), insufficient (30-49.9 nmol/L), sufficient (50-75 nmol/L), or high (>75 nmol/L). Sleep duration was grouped as inadequate (ISD) if < 7 or ≥9 h. Linear and logistic regression were used to calculate unstandardized ß-values and odds ratios [95% confidence intervals]. The analyses were adjusted for season, age, BMI, lifestyle factors and relevant comorbidities. Results: In both men and women, s-25(OH)D was positively associated with sleep duration, and compared to the sufficient s-25(OH)D group, the insufficient s-25(OH)D group reported significantly shorter sleep duration in both sexes. There was an increased odds of ISD in both men and women but adjusted for confounding factors this was only significant in women (1.16 [1.03, 1.32], p = .017). In men, there were no significant associations between s-25(OH)D and the remaining sleep measures. Women in the high s-25(OH)D group had lower ESS-scores (-0.28 [-0.47, -0.08], p = .006), but higher odds of insomnia (1.16 [1.01, 1.33], p = .036) compared to women in the sufficient group. Conclusions: In this Arctic population, a tenuous association was found between s-25(OH)D and subjective sleep measures, predominantly in women.

No improvement of sleep from vitamin D supplementation: insights from a randomized controlled trial.

BACKGROUND: Vitamin D has been linked to sleep health in observational studies. Data from randomized controlled trials (RCTs) with vitamin D is scarce. METHODS: This study presents the results of a secondary analysis of 189 vitamin D insufficient participants (47.1% women) in a previously performed RCT, of which 92 were randomized to vitamin D (100,000 IU (2500 µg) as a bolus dose followed by 20,000 IU (500 µg) per week), and 97 to placebo. At baseline and after 4 months at the end of the study serum 25-hydroxyvitamin D (s-25(OH)D) was measured, and the study questionnaire assessing sleep duration, daytime sleepiness, and symptoms of insomnia, was completed. RESULTS: At baseline, mean s-25(OH)D was 35.0 ± 11.8 and 35.5 ± 13.3 nmol/L in the vitamin D and placebo groups, respectively. After four months, we found no statistically significant differences between the intervention groups in any of the assessed sleep outcomes, neither when stratified by sex, nor when performed in subgroups based on baseline or end of study s-25(OH)D level or presence of sleep complaints at baseline. CONCLUSIONS: We were not able to demonstrate a significant effect of vitamin D supplementation on sleep in this vitamin D insufficient population.

Baseline serum 25-hydroxyvitamin D concentrations in the Tromsø Study 1994-95 and risk of developing type 2 diabetes mellitus during 11 years of follow-up.

AIMS: We wanted to test the hypothesis that low serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with increased risk of developing Type 2 diabetes mellitus (DM) in a population-based cohort during 11 years of follow-up. METHODS: The analyses included 4157 non-smokers and 1962 smokers from the Tromsø Study 1994-95 without diabetes at baseline. Subsequent Type 2 DM was defined using a hospital journal-based end-point registry, completed through the year 2005. Participants were allocated into quartiles of serum 25(OH)D within each month to account for seasonal variation, and serum 25(OH)D values both as a continuous variable and in quartiles were used in Cox regression models. The analyses were stratified by smoking. Adjustments were made for age, sex, body mass index (BMI), physical activity and, in non-smokers, former smoking. RESULTS: Type 2 DM was registered in 183 non-smoking and 64 smoking participants. Using the fourth (highest) quartile of serum 25(OH)D as the reference, non-smoking participants in the third, second and first quartiles had age- and sex-adjusted hazard ratios (95% confidence intervals) of incident Type 2 DM of 1.00 (0.62-1.61), 1.50 (0.97-2.31) and 1.89 (1.25-2.88), respectively, whereas the corresponding values for smokers were 1.79 (0.77-4.19), 2.33 (1.02-5.35) and 2.68 (1.18-6.08). Adjustment for BMI attenuated the hazard ratios, and they were no longer significant. CONCLUSIONS: Baseline serum 25(OH)D was inversely associated with subsequent Type 2 DM in a population-based 11 year follow-up study, but not after adjustment for BMI. Randomized trials are needed to define the possible role of serum 25(OH)D status, and thereby the role of supplementation, in the prevention of Type 2 DM.

Serum cholecalciferol may be a better marker of vitamin D status than 25-hydroxyvitamin D.

Vitamin D is produced in the skin upon sun-exposure or obtained through the diet. Vitamin D is hydroxylated to 25-hydroxyvitamin D (25(OH)D) in the liver and to the active form 1,25-dihydroxyvitamin D (1,25(OH)2D) in the kidneys. To exert its effect 1,25(OH)2D has to bind to the nuclear vitamin D receptor VDR. Lack of vitamin D leads to rickets in children and to osteomalacia in adults. 25(OH)D is used as a marker of a subject's vitamin D status. Low serum 25(OH)D levels are associated with a number of diseases, risk factors for disease and increased mortality. However, intervention studies with vitamin D have generally been disappointing. Many, if not most cells have the hydroxylases necessary for intra-cellular activation of vitamin D. It is likely that more vitamin D diffuses or are transported into the cells than 25(OH)D and 1,25(OH)2D, and accordingly, most of the 1,25(OH)2D that bind to the VDR are derived from intra-cellular hydroxylation of vitamin D. Therefore, our hypothesis is that serum vitamin D is a better marker of a subject's vitamin D status than 25(OH)D. Since the half-life in serum for vitamin D is approximately one day, giving vitamin D weekly or monthly will result in short-lived serum vitamin D peaks with periods of vitamin D deficiency in between. On the other hand, serum 25(OH)D, which has a half-life of weeks, will show high and stable serum levels throughout. Important vitamin D effects may have been missed in studies with intermittent dosing, and vitamin D in intervention trials should be given daily. Likewise, in epidemiological studies and clinical practice 25(OH)D has uniformly been used as marker. This may lead to gross misclassification of individuals that do not have a stable influx of vitamin D from sun-exposure or diet. In epidemiological studies serum vitamin D should be measured as well as 25(OH)D, and in clinical practice a 25(OH)D measurement should be interpreted in view of recent sun-exposure and diet history.

Distribution and determinants of retinol in Norwegian adolescents, and its relation to bone mineral density: the Tromsø Study: Fit Futures.

BACKGROUND/OBJECTIVES: Sufficient vitamin A levels are important for many functions-and both too little and too much may have detrimental health effects. The aim of the study was to describe the distribution of retinol levels in Norwegian adolescents, the relation between lifestyle factors and retinol levels, and the relation between retinol levels and bone mineral density (BMD). SUBJECTS/METHODS: Serum retinol was measured in 414 girls and 474 boys aged 15-19 years, participating in the Tromsø Study: Fit Futures. Questionnaires regarding health and lifestyle factors were filled in, and physical examinations, body composition, and bone mineral density measurements (DEXA) performed. Multiple regression analyses were used to discover associations between retinol and exposure variables. RESULTS: Retinol levels ranged from 0.26 to 6.46 µmol/L with a median (2.5-97.5 percentile) of 2.35 (1.01-4.67) µmol/L. There was no gender difference. In the multivariate models, fat mass, albumin level, physical activity, and lunch habits were positively associated with retinol levels in boys. In girls, fat mass and height were negatively associated with retinol levels, and lean mass, vitamin D, calcium, total cholesterol, and the use of contraceptives were positively associated with retinol levels (p < 0.05). The models explained 18.3% and 14.6% of the variation (R2) in girls and boys, respectively. Retinol levels were not independently associated with BMD. CONCLUSION: Retinol levels in Norwegian adolescents are higher than reported elsewhere, and are to a low degree explained by lifestyle and physical measurements. No independent association with BMD was found.

C-reactive protein, obesity, and the risk of arterial and venous thrombosis.

UNLABELLED: Essentials We performed repeated measurements of C-reactive protein (CRP) and obesity in a cohort study. CRP was associated with risk of myocardial infarction and venous thromboembolism. CRP was a mediator for risk of myocardial infarction in obese men and women. CRP was a partial mediator for risk of venous thromboembolism in obese women, but not in men. SUMMARY: Background Low-grade inflammation in obesity may be a shared pathway for the risk of venous thromboembolism (VTE) and myocardial infarction (MI). Objectives To investigate the associations between repeated measurements of C-reactive protein (CRP) and the risks of MI and VTE, and to explore whether CRP mediated these risks in obese subjects. Methods CRP and obesity measures were collected from 15 134 subjects who participated in one or more surveys of the Tromsø study in 1994-1995, 2001-2002, or 2007-2008. Incident VTEs and MIs were registered until 1 January 2011. Time-varying Cox regression models were used to calculate hazard ratios of MI and VTE according to categories of CRP and obesity measures. Results There were 291 VTEs and 920 MIs during follow-up. High levels of CRP (≥ 3 mg L(-1) versus < 1 mg L(-1) ) were associated with increased risks of MI (hazard ratio [HR] 1.73; 95% confidence interval [CI] 1.32-2.26) and VTE (HR 1.84; 95% CI 1.22-2.78) in women, but only with MI in men (HR 1.93; 95% CI 1.53-2.44). All obesity measures showed stronger associations with CRP in women than in men. In obese women (body mass index [BMI] of ≥ 30 kg m(-2) versus < 25 kg m(-2) ), adjustment for CRP attenuated the risk estimate for VTE by 22%, whereas the incidence rates of VTE increased with combined categories of higher BMI and CRP. No association was found in men. Conclusions Our findings suggest that low-grade inflammation, assessed by measurement of CRP, is associated with the risks of MI and VTE, and may be a shared pathway for MI and VTE in obesity.

Serum levels of vitamin D are not associated with future risk of venous thromboembolism. The Tromsø Study.

Previous studies have provided indirect evidence for a possible association between vitamin D status and risk of venous thromboembolism (VTE). However, no study has so far investigated the association between serum levels of 25-hydroxyvitamin D (25(OH)D), the biomarker of vitamin D status, and risk of VTE. The aim of our study was to investigate whether high levels of 25(OH)D were associated with decreased risk of VTE in a prospective population-based study. Serum levels of 25(OH)D were measured in 6,021 men and women, aged 25-84 years, who participated in the Tromsø Study in 1994-1995. Incident VTE-events were registered from date of inclusion through the end of follow-up, September 1, 2007. Cox-regression models were used to calculate hazard ratios (HR) with 95% confidence interval (CI) for VTE. There were 201 incident VTE-events during a median of 10.7 years of follow-up. The risk of VTE did not decrease per one standard deviation (SD) (19.8 nmol/l) increase in serum 25(OH)D (multivariable HR 1.02; 95% CI 0.91-1.22). Moreover, subjects with serum 25(OH)D ≥ 70 nmol/l (upper quartile) did not have decreased risk of VTE compared to those ≤ 44 nmol/l (lower quartile) in age- and sex-adjusted analysis (HR 0.91, 95% CI: 0.60-1.37, p for trend across quartiles 0.9) or multivariable analysis adjusted for age, sex, body mass index, smoking, and physical activity (HR 0.76, 95% CI: 0.45-1.28, p for trend across quartiles 0.9). Subgroup analyses showed no associations between serum levels of 25(OH)D and unprovoked or provoked VTE. In conclusion, in our study, normal serum levels of 25(OH)D were not associated with future risk of VTE, suggesting that vitamin D status does not play an important role in the pathogenesis of VTE. However, our findings did not apply to subjects with vitamin D deficiency (< 30 nmol/l) due to lack of statistical power among these subjects.

High serum 25-hydroxyvitamin D concentrations are associated with a favorable serum lipid profile.

BACKGROUND/OBJECTIVES: Low serum 25-hydroxyvitamin D (25(OH)D) concentrations are related to increased mortality. One possible explanation could be an association between serum 25(OH)D and serum lipids. SUBJECTS/METHODS: The study was performed at the University of Tromsø, Northern Norway. In total, 8018 nonsmoking and 2087 smoking subjects were included in a cross-sectional study performed in 2008, and 1762 nonsmoking and 397 smoking subjects in a longitudinal study from 1994/1995 to 2008. Nonfasting serum 25(OH)D, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio and triacylglycerol (TAG) were measured. RESULTS: After adjustment for gender, age, sample month and body mass index in the cross-sectional study, there was a significant increase in serum TC, HDL-C and LDL-C, and a significant decrease in serum LDL-C/HDL-C ratio and TAG across increasing serum 25(OH)D quartiles. For serum HDL-C and TAG in nonsmokers the differences between the means for the highest and lowest serum 25(OH)D quartiles were 6.0 and 18.5%, respectively. In the longitudinal study, an increase in serum 25(OH)D was associated with a significant decrease in serum TAG. CONCLUSIONS: There is a cross-sectional association between serum 25(OH)D and serum lipids, and a longitudinal association over 14 years between serum 25(OH)D and TAG, which may contribute to explain the relation between low serum 25(OH)D concentrations and mortality.