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.

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.

Thyroid homeostasis in mother-child pairs in relation to maternal iodine status: the MISA study.

BACKGROUND/OBJECTIVES: Iodine deficiency during pregnancy may influence maternal and foetal thyroid function with the risk of causing neurocognitive and psychomotor deficits in the offspring. The objective of this study was to assess iodine status in pregnant women from Northern Norway and to investigate the influence of iodine status on maternal and infant thyroid function. SUBJECTS/METHODS: Women from the Northern Norway Mother-and-Child contaminant Cohort Study (MISA) donated a blood and urine sample at three visits during their pregnancy and postpartum period (in second trimester, 3 days and 6 weeks after delivery. N=197). Women were assigned to iodine status groups according to urine iodine concentrations (UICs) in second trimester and mixed effects linear models were used to investigate potential associations between iodine status and repeated measurements of thyroid-stimulating hormone (TSH), thyroid hormones (THs), TH-binding proteins and thyroid peroxidase antibodies. Associations between maternal iodine status and TSH in heel prick samples from the infants were investigated with linear regression. RESULTS: Median UIC in second trimester was 84 µg/l (range 18-522) and 80% had UIC below recommended level (<150 µg/l). Iodine-deficient women had higher concentrations of T3, FT3 and FT4 (estimated differences (confidence intervals) of 0.10 nmol/l (0.01, 0.17), 0.16 pmol/l (0.05, 0.26) and 0.45 pmol/l (0.10, 0.78), respectively) compared with iodine-sufficient women. The concentrations varied within normal reference ranges, but the majority of women with subclinical hypothyroidism were iodine deficient. Maternal iodine status did not influence infant TSH concentrations. CONCLUSIONS: This study indicate iodine deficiency among pregnant women in Norway. Iodine status during pregnancy influences maternal thyroid homeostasis and is therefore a risk factor for foetal and infant development.

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.

Large Individual Differences in Serum 25-Hydroxyvitamin D Response to Vitamin D Supplementation: Effects of Genetic Factors, Body Mass Index, and Baseline Concentration. Results from a Randomized Controlled Trial.

The main aim of the study was to determine the influence of genetic factors on the serum 25-hydroxyvitamin D response to vitamin D supplementation. The main outcome measure was an increase in serum 25-hydroxyvitamin D after vitamin D supplementation. The patients are part of a randomized controlled trial in individuals with prediabetes assigned to 20 000 IU of vitamin D3 per week or placebo for 12 months. A total of 484 subjects were included in the analyses and genotyped for single nucleotide polymorphisms in the DBP, DHCR7, CYP2R1, and CYP24A1 genes. Single nucleotide polymorphisms from all 4 selected genes were significantly related to baseline serum 25-hydroxyvitamin D concentrations with differences between major and minor homozygote genotypes ranging from 4.4 to 19.2 nmol/l. In the subjects given vitamin D, those with genotypes with the highest baseline 25-hydroxyvitamin D concentration also had the highest 25-hydroxyvitamin D concentration after 12 months, and the increase (delta) in 25-hydroxyvitamin D was significantly related to 3 of the single nucleotide polymorphisms. The increase in serum 25-hydroxyvitamin D was also higher in lean vs. obese subjects, and higher in those with low baseline 25-hydroxyvitamin D concentrations. When combining these 3 factors in a linear regression model, the predicted (and observed) difference in 25-hydroxyvitamin D increase between high and low responders to the supplementation was approximately 60 nmol/l. In conclusion, due to genetic, body mass, and baseline 25-hydroxyvitamin D differences, there are huge individual variations in the serum 25-hydroxyvitamin D response to vitamin D supplementation that could be of clinical importance.

Hyperglycemia, assessed according to HbA1c , and future risk of venous thromboembolism: the Tromsø study.

BACKGROUND: HbA1c , a marker of average plasma glucose level during the previous 8-12 weeks, is associated with the future risk of cardiovascular disease and all-cause mortality. OBJECTIVES: To examine the association between hyperglycemia, assessed according to HbA1c , and the future risk of venous thromboembolism (VTE) in a population-based cohort. METHODS: HbA1c was measured in 16 156 unique subjects (25-87 years) who participated in one or more surveys of the Tromsø study (Tromsø 4, 1994-1995; Tromsø 5, 2001-2002; and Tromsø 6, 2007-2008). All subjects were followed, and incident VTE events were recorded up to 31 December 2010. RESULTS: There were 333 validated first VTE events, of which 137 were unprovoked, during a median follow-up of 7.1 years. HbA1c was not associated with the future risk of VTE in analyses treating HbA1c as a continuous variable, or in categorized analyses. The risk of VTE increased by 5% per one standard deviation (0.7%) increase in HbA1c (multivariable-adjusted hazard ratio [HR] 1.05; 95% confidence interval [CI] 0.97-1.14), and subjects with HbA1c  ≥ 6.5% had a 27% higher risk than those with HbA1c  < 5.7% (multivariable-adjusted HR 1.27; 95% CI 0.72-2.26). There was no significant linear trend for an increased risk of VTE across categories of HbA1c (P = 0.27). CONCLUSIONS: Serum levels of HbA1c were not associated with the future risk of VTE in multivariable analysis. Our findings suggest that hyperglycemia does not play an important role in the pathogenesis of VTE.

Single-nucleotide polymorphism, rs1799941 in the Sex Hormone-Binding Globulin (SHBG) gene, related to both serum testosterone and SHBG levels and the risk of myocardial infarction, type 2 diabetes, cancer and mortality in men: the Tromsø Study.

Low testosterone levels are associated with metabolic and cardiovascular disease risk factor, and have been shown to predict type 2 diabetes mellitus (T2DM), myocardial infarction (MI) and all-cause mortality. It is not known if these associations are causal or not. Recently, it has been shown that the serum testosterone levels are associated with single-nucleotide polymorphisms (SNPs), and we therefore studied the associations between one of these SNPs, rs1799941 on the Sex Hormone-Binding Globulin (SHBG) gene, and MI, T2DM, cancer and death. DNA was prepared from men who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints MI, T2DM, cancer or death and a randomly selected control group. For mortality, the observation time was set from 1994, and for the other endpoints from birth. The endpoint data were completed up to 2010-2013. Genetic analyses were successfully performed in 5309 men, of whom 1454 were registered with MI, 638 with T2DM, 1534 with cancer and in 2226 who had died. Men with the minor homozygote genotype had significantly higher levels of total testosterone (14.7%) and SHBG (24.7%) compared with men with the major homozygote genotype, whereas free testosterone levels did not differ significantly between the genotypes. The SNP rs1799941 was not significantly associated with MI, T2DM, cancer or mortality. Thus, our result does not support a causal relationship between total testosterone and SHBG and MI, T2DM, cancer or mortality, suggesting that low testosterone more likely is a marker of poor health.

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.

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.

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.

Glycated hemoglobin in diagnosis of diabetes mellitus and pre-diabetes; validation by oral glucose tolerance test. The Tromsø OGTT Study.

BACKGROUND: Glycated hemoglobin (HbA(1c)) 6.5% has recently been recommended by the World Health Organization (WHO) and the American Diabetes Association (ADA) as an alternative diagnostic criterion for diabetes mellitus (DM). AIM: To evaluate HbA(1c) as an alternative to oral glucose tolerance test (OGTT) for diagnosis of DM and pre-diabetes and to find the optimal HbA(1c) cut-off points for DM and pre-diabetes in our population. SUBJECTS AND METHODS: The subjects were recruited from the Tromsø Study, performed for the 6th time in 2007-2008 with 12,984 participants. All subjects with HbA(1c) in the range 5.8-6.9% and a random sample of subjects with levels 5.3-5.7% were invited to an OGTT. RESULTS: Among 3476 subjects who completed the OGTT, 199 were diagnosed with DM. The best sensitivity (69.8%) and specificity (81.8%) were found at HbA(1c) 6.2%. For HbA(1c) 6.5% we found a sensitivity of 34.7% and specificity 97.1%. The best cut-off points for impaired fasting glucose (no.=314) and impaired glucose tolerance (no.=404) were found at HbA(1c) 5.9% and 6.0%, respectively. Pre-diabetes detected only by OGTT was associated with worse metabolic characteristics than pre-diabetes detected only by HbA(1c). CONCLUSIONS: The optimum HbA(1c) cutoff point for DM in our population was lower than that proposed by WHO and ADA. To establish more precisely the HbA(1c) levels predictive of micro- and macro-vascular complications, long-term prospective studies are needed. Population- specific optimum cut-off points may be necessary.

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.

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.

No improvement in cardiovascular risk factors in overweight and obese subjects after supplementation with vitamin D3 for 1 year.

BACKGROUND AND AIM: Cross-sectional studies indicate vitamin D to be of importance for glucose tolerance, blood pressure and serum lipids, but whether supplementation with vitamin D would improve cardio-vascular risk factors is not known. DESIGN AND SETTING: The study was a 1 year, double blind placebo-controlled intervention trial performed at the University Hospital of North Norway from November 2005 to October 2007. Subjects. A total of 438 overweight or obese subjects, 21-70 years old, were included and 330 completed the study. INTERVENTIONS: The subjects were randomized to vitamin D (cholecalciferol, vitamin D(3)) 40 000 IU per week (DD group), vitamin D 20 000 IU per week (DP group), or placebo (PP group). All subjects were given 500 mg calcium daily. MAIN OUTCOME MEASURES: Fasting serum lipids and blood pressure were measured and an oral glucose tolerance test performed at start and end of the study. RESULTS: At baseline the mean serum 25(OH)D levels were 58 nmol L(-1) (all subjects) and increased to 140 and 101 nmol L(-1) in the DD and DP groups, respectively. No significant differences were found between the three groups regarding change in measures of glucose metabolism or serum lipids. In the DP group, there was a slight but significant increase in systolic blood pressure compared with the placebo group. CONCLUSIONS: Our results do not support a positive effect of vitamin D on glucose tolerance, blood pressure or serum lipids. Further studies in subjects with low serum 25(OH)D levels combined with impaired glucose tolerance, hypertension or dyslipidaemia are needed.

Prevalence and causes of undiagnosed hyperthyroidismin an adult healthy population. The Tromsø study.

BACKGROUND: The causes of subclinical hyperthyroidism have only been reported from clinical studies. AIM: To determine the prevalence and pathological causes of reduced serum TSH levels in subjects recruited from an epidemiological survey. MATERIAL/SUBJECTS AND METHODS: Serum TSH was measured in 7954 subjects in the 5th Tromsø study. Subjects with serum TSH<0.50 mIU/l, not using T4, without a previous diagnosis of thyroid disease, without serious concomitant disease, and younger than 80 yr, were invited for a re-examination. If low serum TSH was persistent, thyroid scintigraphy was performed. RESULTS: Among the 4962 subjects that met the inclusion criteria, serum TSH was <0.50 mIU/l in 105 subjects. Twelve subjects had a suppressed serum TSH level (<0.05 mIU/l). Two of these were lost to follow-up, 4 had Graves' disease, 4 had adenoma, and 2 had multinodular goiter. In the 93 subjects with serum TSH 0.05-0.5 mIU/l, 55 were re-examined, of whom 35 had normalized their serum TSH level. In the remaining 20 subjects, 1 had Graves' disease, 6 had adenoma (of which 2 were toxic adenomas), 7 had multinodular goiter, and 6 were considered normal. Among the 521 subjects using T4, 70 (13.4%) had a suppressed serum TSH level. CONCLUSIONS: Most of the subjects with a suppressed serum TSH level will be on T4 medication. Otherwise, if the suppressed serum TSH level is found by chance, this probably represents a clinically important thyroid pathology. Also, in subjects with a persistently low serum TSH level (0.05-0.5 mIU/l) most will have a pathological thyroid scan.

Supplementation with cholecalciferol does not result in weight reduction in overweight and obese subjects.

OBJECTIVE: Investigate whether cholecalciferol supplementation leads to weight loss in overweight and obese adults. DESIGN: Randomized double blind clinical trial with 20,000 IU cholecalciferol twice a week, or 20,000 IU once a week plus placebo, or placebo twice a week, for 12 months. All subjects were given 500 mg calcium supplementation. METHODS: Four hundred and forty five healthy, overweight, and obese men and women (age 21-70 years, body mass index (BMI) 28.0-47.0 kg/m(2)). Body weight, fatness, and fat distribution parameters were measured by dual-energy X-ray absorptiometry and anthropometry, blood samples and 24-h urinary samples were collected. RESULTS: At baseline, there were no significant differences between the groups, but there was a significant inverse relation between serum 25-hydroxyvitamin D (25(OH)D) levels and BMI, and a significant positive association between calorie intake and BMI. Three hundred and thirty four subjects completed the study. During the study, there was no significant change in weight, waist-to-hip ratio (WHR) or percentage body fat in any of the groups, nor between them. Parathyroid hormone decreased and 25(OH)D increased significantly in both groups receiving cholecalciferol, and serum levels of 25(OH)D stabilized after 3 months. Serum calcium was unchanged in all groups. Urinary calcium excretion increased in all groups, but there was no significant difference between the groups. Weekly dosage of 20,000-40,000 IU cholecalciferol for 12 months was associated with a low risk of adverse effects, at least in overweight and obese adults living at latitude 70 degrees N. CONCLUSION: Significant weight reduction in overweight and obese subjects is unlikely to occur with cholecalciferol supplementation.

Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial.

OBJECTIVES: The objective of the present study was to examine the cross-sectional relation between serum 25-hydroxyvitamin D [25-(OH) D] levels and depression in overweight and obese subjects and to assess the effect of vitamin D supplementation on depressive symptoms. DESIGN: Cross-sectional study and randomized double blind controlled trial of 20,000 or 40,000 IU vitamin D per week versus placebo for 1 year. SETTING: A total of 441 subjects (body mass index 28-47 kg m(-2), 159 men and 282 women, aged 21-70 years) recruited by advertisements or from the out-patient clinic at the University Hospital of North Norway. MAIN OUTCOME MEASURES: Beck Depression Inventory (BDI) score with subscales 1-13 and 14-21. RESULTS: Subjects with serum 25(OH)D levels < 40 nmol L(-1) scored significantly higher (more depressive traits) than those with serum 25(OH)D levels > or = 40 nmol L(-1) on the BDI total [6.0 (0-23) versus 4.5 (0-28) (median and range)] and the BDI subscale 1-13 [2.0 (0-15) versus 1.0 (0-29.5)] (P < 0.05). In the two groups given vitamin D, but not in the placebo group, there was a significant improvement in BDI scores after 1 year. There was a significant decrease in serum parathyroid hormone in the two vitamin D groups without a concomitant increase in serum calcium. CONCLUSIONS: It appears to be a relation between serum levels of 25(OH)D and symptoms of depression. Supplementation with high doses of vitamin D seems to ameliorate these symptoms indicating a possible causal relationship.

Cross-sectional study on the relationship between body mass index and smoking, and longitudinal changes in body mass index in relation to change in smoking status: the Tromso Study.

AIMS: To evaluate the effects of smoking and other lifestyle factors on body mass index (BMI), and changes in BMI in relation to changes in smoking status. METHODS: A cross-sectional study was performed on 10,920 males (3937 smokers) and 12,090 females (4343 smokers) who participated in the fourth Tromsø Study (performed in 1994-95). A longitudinal study was performed on 2364 males (732 smokers in 1994-95) and 2738 females (942 smokers in 1994-95) who participated in both the fourth and the fifth Tromsø studies (performed in 2001). RESULTS: In the cross-sectional study, current smokers of both genders had a lower BMI (25.0+/-3.4 vs. 25.5+/-3.2 kg/m(2) in males, and 23.9+/-3.9 vs. 25.3+/-4.6 kg/m( 2) in females, p<0.01), a lower degree of physical activity, and a higher consumption of coffee and alcohol than never-smokers. We found a U-shaped relationship between number of cigarettes smoked per day and BMI, with the lowest BMI in those smoking 6- 10 cigarettes per day. Heavy smokers and never-smokers had similar BMI. In the longitudinal study, continuing smokers had a smaller increase in BMI than those who gave up smoking. In those who gave up smoking, there was a significant, positive relationship between number of cigarettes smoked in 1994-95 and increase in BMI. CONCLUSIONS: There is a U-shaped relationship between number of cigarettes smoked per day and BMI. Smoking cessation is associated with an increase in weight as compared to those who continue smoking.