The association between serum 25-hydroxyvitamin D levels and psoriasis in a large population-based cohort: a cross-sectional analysis of The Tromsø Study 2015-16.

BACKGROUND: Case-control studies indicate an association between lower serum 25-hydroxyvitamin D [25(OH)D] levels and psoriasis. Data from larger population-based cohorts including mild cases are sparse. OBJECTIVES: To investigate the association between 25(OH)D and psoriasis in a large population-based cohort, and assess possible effect modification by overweight. METHODS: Data from the Tromsø Study 2015-16 (Tromsø7), which included 19 520 participants from the general population aged 40-79 years, were subjected to a cross-sectional analysis. We assessed the shapes of the relationships between 25(OH)D and psoriasis using fractional polynomials. Odds ratios (ORs) for lifetime and active psoriasis were estimated using logistic regression. Adjusted models included month of blood sampling, body mass index (BMI), age and sex. Two-way and additive interaction between BMI and 25(OH)D were explored. RESULTS: From a total of 19 520 participants [10 203 women (52.3%); mean age 56.3 years (SD 10.4); mean 25[OH]D, 63.4 nmol L-1 (SD 21.9)], 2088 (10.7%) reported lifetime psoriasis and 1179 (6.0%) reported active psoriasis the past 12 months. There was no association between 25(OH)D and lifetime psoriasis [OR per 10 nmol L-1 increase in 25(OH)D 1.02, 95% confidence interval (CI) 0.99-1.04]. The relationship between 25(OH)D and active psoriasis was suggested to be nonlinear, but the model was not significant (P = 0.098). There was evidence for a superadditive effect (i.e. larger than the sum of the factors) of BMI > 27.5 kg m-2 and 25(OH)D < 25 nmol L-1 on the odds for active psoriasis (OR 1.92, 95% CI 1.18-3.12), but not for lifetime psoriasis (OR 1.41, 95% CI 0.93-2.15). There was no evidence for two-way interaction between BMI and 25(OH)D. CONCLUSIONS: This large population-based study found no significant relationship between 25(OH)D and psoriasis. The analysis may have been underpowered to detect a threshold effect in the lower 25(OH)D spectrum. Interaction analysis indicates that high BMI and vitamin D deficiency combined increase the odds of active psoriasis more than the sum of these factors, with an estimated 92% higher odds for active psoriasis in participants with BMI > 27.5 kg m-2 and 25(OH)D < 25 nmol L-1. Providing advice to prevent vitamin D deficiency may be considered in the follow-up of overweight patients with psoriasis.

Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials.

BACKGROUND: The role of vitamin D in people who are at risk for type 2 diabetes remains unclear. PURPOSE: To evaluate whether administration of vitamin D decreases risk for diabetes among people with prediabetes. DATA SOURCES: PubMed, Embase, and ClinicalTrials.gov from database inception through 9 December 2022. STUDY SELECTION: Eligible trials that were specifically designed and conducted to test the effects of oral vitamin D versus placebo on new-onset diabetes in adults with prediabetes. DATA EXTRACTION: The primary outcome was time to event for new-onset diabetes. Secondary outcomes were regression to normal glucose regulation and adverse events. Prespecified analyses (both unadjusted and adjusted for key baseline variables) were conducted according to the intention-to-treat principle. DATA SYNTHESIS: Three randomized trials were included, which tested cholecalciferol, 20 000 IU (500 mcg) weekly; cholecalciferol, 4000 IU (100 mcg) daily; or eldecalcitol, 0.75 mcg daily, versus matching placebos. Trials were at low risk of bias. Vitamin D reduced risk for diabetes by 15% (hazard ratio, 0.85 [95% CI, 0.75 to 0.96]) in adjusted analyses, with a 3-year absolute risk reduction of 3.3% (CI, 0.6% to 6.0%). The effect of vitamin D did not differ in prespecified subgroups. Among participants assigned to the vitamin D group who maintained an intratrial mean serum 25-hydroxyvitamin D level of at least 125 nmol/L (≥50 ng/mL) compared with 50 to 74 nmol/L (20 to 29 ng/mL) during follow-up, cholecalciferol reduced risk for diabetes by 76% (hazard ratio, 0.24 [CI, 0.16 to 0.36]), with a 3-year absolute risk reduction of 18.1% (CI, 11.7% to 24.6%). Vitamin D increased the likelihood of regression to normal glucose regulation by 30% (rate ratio, 1.30 [CI, 1.16 to 1.46]). There was no evidence of difference in the rate ratios for adverse events (kidney stones: 1.17 [CI, 0.69 to 1.99]; hypercalcemia: 2.34 [CI, 0.83 to 6.66]; hypercalciuria: 1.65 [CI, 0.83 to 3.28]; death: 0.85 [CI, 0.31 to 2.36]). LIMITATIONS: Studies of people with prediabetes do not apply to the general population. Trials may not have been powered for safety outcomes. CONCLUSION: In adults with prediabetes, vitamin D was effective in decreasing risk for diabetes. PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42020163522).

Lost relation between blood pressure and serum 25-hydroxyvitamin D.

BACKGROUND: Low serum 25-hydroxyvitamin D (25(OH)D) levels have consistently been associated with hypertension. During the last decades there has been an unexplained reduction in blood pressure (BP) in Western countries. We therefore examined the relation between serum 25(OH)D and BP in the 7th survey of the Tromsø study 2015/2016. METHODS: Blood pressure and serum 25(OH)D were measured and life-style factors registered in 15,951 subjects not using BP medication. RESULTS: In unadjusted analyses there was a significant negative association between serum 25(OH)D and systolic and diastolic BP that disappeared after adjusting for relevant confounders. This finding is in contrast to our previous reports on 25(OH)D and BP. We therefore cross-sectionally re-analyzed non-smoking (due to interference by smoking in the 25(OH)D assay) subjects not using BP medication from the 4th survey in 1994/1995 (n = 4108), 6th survey in 2007/2008 (n = 7553) and 7th survey 2015/2016 (n = 13,413). Adjusting for age and BMI, there were significant inverse relations between BP and 25(OH)D in the 4th, to a lesser degree in the 6th, and none in the 7th survey. For males the age- and BMI-adjusted differences in systolic BP between those with serum 25(OH)D < 25 nmol/L versus serum 25(OH)D > 100 nmol/L were 6.2 mmHg, 4.1 mmHg and -0.1 mmHg, for the 4th, 6th and 7th surveys, respectively. CONCLUSIONS: Concomitant with a substantial reduction in BP from 1994 to 2015, there has been a loss of relation between 25(OH)D and BP which is hard to explain.

Creatine kinase in relation to body fat in a Caucasian overweight and obese population.

We investigated the association between serum creatine kinase (CK) and body fat mass in an overweight and obese population. In this cross-sectional study, 454 Caucasian overweight and obese individuals recruited from a medical outpatient clinic and via newspaper advertising underwent dual-energy X-ray absorptiometry (DEXA). Serum CK was obtained along with supplementary blood samples. This report is based on a secondary analysis from a previous randomized controlled trial treating obesity with vitamin D3. Serum CK correlated negatively with body fat mass in men (r = -.18, p = .025) but not in women (r = -.11, p = .069). An insignificant negative trend for logCK across quartiles of fat mass in men was found (p = .098). CK did not associate significantly with lean mass, but lean mass correlated positively with fat mass in both groups (p < .0001). In a multivariate model, serum CK was inversely and independently related to fat mass in men. Fat mass decreased with 7.83 kg per unit logCK increase when adjusted for age and lean mass (95% CI -12.3 to -3.3, p = .001). These data support the view that circulating CK interacts with obesity in a favourable way independent of its muscular connection in men. CK was not associated with fat mass in women.

Bone mineral density at the hip and its relation to fat mass and lean mass in adolescents: the Tromsø Study, Fit Futures.

BACKGROUND: Positive association between body weight and bone mass is well established, and the concept of body mass index (BMI) is associated with higher areal bone mineral density (aBMD) and reduced fracture risk. BMI, that comprises both fat mass (FM) and lean mass (LM) may contribute to peak bone mass achievement in different ways. This study explored the influence of body composition in terms of total body LM and FM on hip aBMD-values in adolescence. METHODS: In 2010/2011, 93% of the region's first-year upper-secondary school students (15-17 years old) in Tromsø, Norway attended the Tromsø Study, Fit Futures. Areal BMD at femoral neck (aBMDFN) and total hip (aBMDTH) (g/cm2), total body LM and FM (g) were measured by dual energy X-ray absorptiometry (DXA). Height and weight were measured, and BMI calculated. Lifestyle variables were collected by self-administered questionnaires and interviews, including questions on time spent on leisure time physical activity. Stratified analyses of covariance and regression models included 395 girls and 363 boys. Crude results were adjusted for age, height, sexual maturation, physical activity levels, vitamin D levels, calcium intake, alcohol consumption and smoking habits. RESULTS: Unadjusted distribution indicated higher aBMD-levels at higher LM-levels in both genders (p < 0.001), but higher aBMD at higher FM-levels were found only in girls (p < 0.018). After multiple adjustments, aBMDFN-levels in girls were associated by 0.053 g/cm2 and 0.032 g/cm2 per standard deviation (SD) change in LM and FM (p < 0.001). Corresponding values in boys were 0.072 and 0.025 (p < 0.001). The high LM groups accounted for the highest aBMD-levels, while aBMD-levels at the LM/FM-combinations indicated different patterns in girls compared to boys. The adjusted odds ratio (95% CI) for low levels of aBMDFN was 6.6 (3.4,13.0) in boys, compared to 2.8 (1.6,4.9) in girls per SD lower LM. CONCLUSIONS: LM and FM should be regarded as strong predictors for bone mass and hence bone strength in adolescents. A gender specific difference indicated that high lean mass is of crucial importance prominently in boys. In adolescents with low lean mass, especially in girls, high fat mass may partially ameliorate the effect of deficient lean mass levels.

Lean body mass and creatine kinase are associated with reduced inflammation in obesity.

BACKGROUND: Obesity is associated with inflammation, but the role of lean mass and creatine kinase (CK) on the inflammatory process is less known. We investigated the associations between lean mass, CK and fat mass upon inflammatory parameters in an overweight and obese adult population. MATERIAL AND METHODS: Body composition examined by dual-energy X-ray absorptiometry, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), CK and supplementary clinical parameters were measured in 454 overweight and obese individuals. This is a secondary analysis from a cohort of obese individuals treated with Vitamin D. RESULTS: Mean age was 47·6 ± 11·4 years and mean body mass index 34·6 ± 3·9 kg/m2 . Lean mass correlated negatively with hs-CRP (r = -0·127, P = 0·042) and ESR (r = -0·381, P < 0·001). Median lean mass in the lower ESR quartile was significantly higher than in the upper quartile (P < 0·001) but not between lower and upper hs-CRP quartiles (P = 0·114). CK was negatively correlated with hs-CRP (r = -0·151, P < 0·001) and ESR (r = -0·240, P < 0·001). Median CK in the lower hs-CRP and ESR quartiles were significantly higher than in the upper quartiles (P < 0·001 for both). Conversely, fat mass was positively associated with hs-CRP and ESR. CONCLUSIONS: Inflammatory parameters were related to reduced lean mass and CK in an overweight and obese population. Hypothetically, lean mass has a favourable effect on obesity-related inflammation, and CK may play a role as an inhibitor of inflammation in obesity.

Small and large fiber neuropathy in those with type 1 and type 2 diabetes: a 5-year follow-up study.

The purpose of this study was to evaluate progression of diabetic polyneuropathy and differences in the spectrum and evolution of large- and small-fiber involvement in patients with diabetes type 1 and 2 over 5 years. Fifty-nine patients (35 type 1 and 24 type 2) were included. Nerve conduction studies (NCS), quantitative sensory testing, skin biopsy for quantification of intraepidermal nerve fiber density (IENFD), symptom scoring and clinical evaluations were performed. Z-scores were calculated to adjust for the physiologic effects of age and height/gender. Neuropathic symptoms were not significantly more frequent in type 2 than in type 1 diabetic patients at follow-up (54% vs. 37%). The overall mean NCS Z-score remained within the normal range, but there was a small significant decline after 5 years in both groups: type 1 (p = 0.004) and type 2 (p = 0.02). Mean IENFD Z-scores changed from normal to abnormal in both groups, but only significantly in those with type 2 diabetes (reduction from 7.9 ± 4.8 to 4.3 ± 2.8 fibers/mm, p = 0.006). Cold perception threshold became more abnormal only in those with type 2 diabetes (p = 0.049). There was a minimal progression of large fiber neuropathy in both groups. Reduction of small fibers predominated and progressed more rapidly in those with type 2 diabetes.

Vitamin D deficiency is common in psychogeriatric patients, independent of diagnosis.

BACKGROUND: Previous studies have found an association between psychiatric disorders and vitamin D deficiency, but most studies have focused on depression. This study aimed to establish the prevalence of vitamin D deficiency in elderly patients with a wider range of psychiatric diagnoses. METHOD: The study included elderly patients (>64 years) referred to a psychiatric hospital in Northern Norway and a control group from a population survey in the same area. An assessment of psychiatric and cognitive symptoms and diagnoses was conducted using the Montgomery and Aasberg Depression Rating Scale, the Cornell Scale for Depression in Dementia, the Mini Mental State Examination, the Clockdrawing Test, and the Mini International Neuropsychiatric Interview (MINI+), as well as clinical interviews and a review of medical records. The patients' mean level of 25-hydroxyvitamin D (25(OH)D) and the prevalence of vitamin D deficiency were compared with those of a control group, and a comparison of vitamin D deficiency across different diagnostic groups was also made. Vitamin D deficiency was defined as 25(OH)D <50 nmol/L (<20 ng/ml). RESULTS: The mean levels of 25(OH)D in the patient group (n = 95) and the control group (n = 104) were 40.5 nmol/L and 65.9 nmol/L (p < 0.001), respectively. A high prevalence of vitamin D deficiency was found in the patient group compared with the control group (71.6% and 20.0%, respectively; p < 0.001). After adjusting for age, gender, season, body mass index, and smoking, vitamin D deficiency was still associated with patient status (OR: 12.95, CI (95%): 6.03-27.83, p < 0.001). No significant differences in the prevalence of vitamin D deficiency were found between patients with different categories of psychiatric diagnoses, such as depression, bipolar disorders, psychosis, and dementia. CONCLUSION: Vitamin D deficiency is very common among psychogeriatric patients, independent of diagnostic category. Even though the role of vitamin D in psychiatric disorders is still not clear, we suggest screening for vitamin D deficiency in this patient group due to the importance of vitamin D for overall health.

Serum free and bio-available 25-hydroxyvitamin D correlate better with bone density than serum total 25-hydroxyvitamin D.

In the circulation 25-hydroxyvitamin D (25(OH)D) is bound to vitamin D-binding protein (DBP) and albumin. Only a small fraction is in the unbound, free form. According to the 'free-hormone-hypothesis' only the free form is biologically active. Genetic differences in DBP may affect the binding to 25(OH)D and thereby the amount of free 25(OH)D. In the present study sera were obtained from 265 postmenopausal women with low bone mass density (BMD). Serum 25(OH)D, DBP and albumin were measured and the free and bio-available (free + albumin-bound) 25(OH)D calculated. Based on genotyping of the polymorphisms rs7041 and rs4588, the six common DBP phenotypes were identified and the free and bio-available 25(OH)D calculated according to the corresponding binding coefficients. Relations between measures of 25(OH)D and PTH and BMD were evaluated with linear regression adjusted for age and BMI. The calculated amount of free and bio-available 25(OH)D was 0.03% and 13.1%, respectively, of the measured total serum 25(OH)D. Adjusting for DBP phenotype affected the calculated free and bio-available 25(OH)D levels up to 37.5%. All measures of 25(OH)D correlated significantly with PTH, whereas a significant association with BMD was only seen for the free and bio-available 25(OH)D measures. Adjusting for the DBP phenotypes improved the associations. These relations were almost exclusively seen in subjects not using vitamin D and/or calcium supplements. In conclusion, the free and bio-available forms of 25(OH)D may be a more informative measure of vitamin D status than total 25(OH)D. Adjustment for DBP phenotype may improve this further.

Vitamin D deficiency and lifestyle risk factors in a Norwegian adolescent population.

AIM: The aim was to study vitamin D status in a healthy adolescent Norwegian population at 69°N. METHODS: The data presented come from The Tromsø Study: Fit Futures, during the school year 2010/2011 (not including the summer months), where 1,038 (92% of those invited) participated. Physical examinations, questionnaires and blood samples were collected, and serum 25-hydroxyvitamin D (25(OH)D) were analyzed using LC-MS/MS. RESULTS: RESULTS are presented from 475 boys and 415 girls (15-18 years old) with available blood samples. A total of 60.2% had vitamin D deficiency or insufficiency (serum 25(OH)D <50 nmol/l), 16.5% were deficient (<25 nmol/l) and 1.6% had severe vitamin D deficiency (<12.5 nmol/l). Only 12.4% had levels >75 nmol/l. A significant gender difference with a mean (SD) serum 25(OH)D level of 40.5 (20.5) nmol/l in boys and 54.2 (23.2) nmol/l in girls (p <0.01) was present. Furthermore, 51.3% of girls had levels >50 nmol/l in comparison to 29.7% of boys (p <0.01). There was an inverse correlation between parathyroid hormone levels and 25(OH)D, rs= -0.30 (p<0.01). Explanatory factors that were significantly associated with serum 25(OH)D levels in multivariate models were use of snuff, consumption of vitamin D fortified milk, cod liver oil and vitamin/mineral supplements, physical activity, sunbathing holiday and use of solarium in boys, and vitamin/mineral supplements, physical activity, sunbathing holiday and use of solarium in girls . CONCLUSIONS: Vitamin D deficiency is prevalent during the school year among adolescents in northern Norway, particularly among boys.

A study of the psychometric properties of the Beck Depression Inventory-II, the Montgomery and Åsberg Depression Rating Scale, and the Hospital Anxiety and Depression Scale in a sample from a healthy population.

The objective of this study is to evaluate internal consistency and psychometric properties of the Hospital Anxiety and Depression Scale (HADS), the Beck Depression inventory-II (BDI-II) and the Montgomery and Åsberg Depression Rating Scale (MADRS) for screening for major depressive episode (MDE) in a selected sample from a healthy population. Participants answered the BDI-II and the HADS questionnaires and were interviewed with MADRS. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Axis I Disorders-Clinician Version (SCID-CV) was used to diagnose MDE. Current MDE was diagnosed in 20 (6%) of the 357 participants. All three scales including the depression sub-scale for HADS had high area under the receiver operating characteristics curve (ROC) (AUC) (0.84-0.87), and internal consistency was also high for all scales (0.75-0.89). Optimal cut-off for MDE was ≥ 12 for BDI-II, MADRS ≥ 8, HADS total ≥ 9, and HADS-D ≥ 4, which all resulted in sensitivities = 85% and specificities > 78%. Diagnostic accuracy was low on all depression scales (Cohen's kappa = 0.20-0.40). Reports of the properties of depression scales in a healthy population are limited. We found BDI-II, HADS and MADRS to be acceptable as screening instruments for MDE in a selected sample from healthy population with recommend cut-offs as mentioned above.

Vitamin D Status During Adolescence and the Impact of Lifestyle Changes: 2 Years' Follow-up From the Fit Futures Study.

CONTEXT: Longitudinal data regarding vitamin D status in adolescence is scarce. This study presents population-based data from an Arctic adolescent population (n = 589) at 16 and 18 years. OBJECTIVE: The aims of this study were to investigate changes in vitamin D status during 2 years in adolescence, and whether lifestyle changes were associated with serum 25-hydroxyvitamin D (s-25(OH)D) at follow-up. METHODS: Fit Futures is a longitudinal study at 69°N in Norway. Participants had their s-25(OH)D levels analyzed in their first and third year of upper secondary school (median age 16 and 18 years), in Fit Futures 1 (FF1) and Fit Futures 2 (FF2), respectively. Self-reported lifestyle habits were registered through questionnaires. The association between lifestyle changes and s-25(OH)D levels at follow-up were calculated by regression analyses, controlling for baseline s-25(OH)D levels. RESULTS: Longitudinal data were available for 309 girls and 280 boys. The proportion of adolescents with s-25(OH)D <50 nmol/L were 73.7% in FF1 and 77.1% in FF2, while the proportion <30 nmol/L constituted 35.7% in FF1 and 40.9% in FF2. Of those with s-25(OH)D <30 nmol/L (severe vitamin D deficiency) in FF1, 73.3% remained severely deficient in FF2. Among boys, an increase in UV exposure was significantly associated with higher s-25(OH)D levels in FF2 (beta; CI [nmol/L] 12.9; 9.1, 16.7). In girls, decreased vitamin/mineral supplement intake was significantly associated with lower s-25(OH)D at FF2 (-6.7; -10.2, -3.1), while increased UV (10.8; 7.0, 14.7) and combined hormonal contraceptive exposure (12.1; 6.0, 18.1) in FF2 was significantly associated with higher s-25(OH)D levels in FF2. CONCLUSION: Severe vitamin D deficiency was prevalent throughout adolescence. Lifestyle changes may alter s-25(OH)D levels in this age group.

Serum calcium and the calcium-sensing receptor polymorphism rs17251221 in relation to coronary heart disease, type 2 diabetes, cancer and mortality: the Tromsø Study.

Serum calcium measured in 27,158 subjects in 1994 and the calcium-sensing receptor polymorphism rs17251221 genotyped in 9,404 subjects were related to cardiovascular risk factors, incident myocardial infarction (MI), type 2 diabetes (T2DM), cancer and death during follow-up until 2008-2010. In a Cox regression model with adjustment for age, gender, smoking and body mass index, subjects with serum calcium 2.50-2.60 mmol/L had a significantly increased risk of incident MI [n = 1,802, hazards ratio (HR) 1.40, 95 % confidence interval (CI) 1.18, 1.66] and T2DM (n = 705, HR 1.49, 95 % CI 1.15, 1.94) and a significantly reduced risk of cancer (n = 2,222, HR 0.73, 95 % CI 0.62, 0.86) as compared to subjects with serum calcium 2.20-2.29 mmol/L. For rs17251221 there was a mean difference in serum calcium of 0.05 mmol/L between major and minor homozygote genotypes. No consistent, significant relation between rs17251221 and risk factors or the major hard endpoints were found. The minor homozygote genotype (high serum calcium) had a significant twofold increased risk (HR 2.32, 95 % CI 1.24, 4.36) for prostate cancer, as compared to the major homozygote. This may be clinically important if confirmed in other cohorts.

Effect of Vitamin D Supplementation on Psoriasis Severity in Patients With Lower-Range Serum 25-Hydroxyvitamin D Levels: A Randomized Clinical Trial.

Importance: Topical vitamin D analogues are routine treatment for psoriasis, but the effect of oral supplementation has not been established. Objective: To examine the effect of vitamin D supplementation on psoriasis severity throughout the winter. Design, Setting, and Participants: This randomized, double-blind placebo-controlled clinical trial with 2 parallel groups was performed through 2 winter seasons (2017 to 2018 and 2018 to 2019). Randomization was computer generated. All participants, health care clinicians, and outcome assessors were masked to group assignment. Each participant was followed for 4 months. The presented analyses were conducted in May 2022. The trial was conducted at the clinical research unit of the University Hospital of North Norway (Tromsø; Norway). Adults from the general population in Tromsø with active plaque psoriasis and 25-hydroxyvitamin D (25[OH]D) levels of less than 24 ng/mL (to convert to nmol/L, multiply by 2.496) were included. Intervention: Vitamin D (cholecalciferol, 100 000 IU, loading dose, followed by 20 000 IU/week) or placebo for 4 months. Main outcomes and Measures: Psoriasis Area Severity Index (PASI) (primary outcome), Physician Global Assessment, self-administered PASI, and Dermatology Life Quality Index scores (secondary outcomes). Results: A total of 122 participants (46 women [37.7%]; mean [SD] age, 53.6 [10.0] years; mean [SD] PASI score, 3.1 [2.0]; mean [SD] serum 25(OH)D, 14.9 [3.9] ng/mL) were included. Of these, 60 (49.2%) were randomized to the vitamin D group and 62 (50.8%) to the placebo group. A total of 120 participants (59 vitamin D [49.2%]/61 placebo [51.8%]) completed the study. By completion, mean (SD) 25(OH)D levels were 29.7 (5.2) ng/mL (vitamin D) and 12.0 (3.8) ng/mL (placebo). There was no significant difference in change in PASI score between the groups (adjusted difference, 0.11; 95% CI, -0.23 to 0.45). There was no significant difference in change in Physician Global Assessment score (adjusted odds ratio, 0.66; 95% CI, 0.27-1.63), self-administered PASI (adjusted difference, -0.60; 95% CI, -1.76 to 0.55) or Dermatology Life Quality Index (adjusted difference, -0.86; 95% CI, -1.9 to 0.19) between the groups. No adverse effects of the intervention were registered. Conclusion and Relevance: The results of this randomized clinical trial showed that vitamin D supplementation did not affect psoriasis severity. Low baseline severity scores may explain the lack of measurable effect. Levels of 25(OH)D in the intervention group increased to a less-than-expected degree based on previous experimental data from the same source population, and this may have affected the results. Trial Registration: ClinicalTrials.gov Identifier: NCT03334136.

Longitudinal changes in vitamin D concentrations and the association with type 2 diabetes mellitus: the Tromsø Study.

AIM: We aimed to investigate the relationship between pre- and post-diagnostic 25-hydroxyvitamin D (25(OH)D) concentrations and type 2 diabetes (T2DM) over a period of 30 years in individuals who developed T2DM compared to healthy controls. METHODS: This case-control study included 254 participants with blood samples collected at five different time-points (T1-T5) between 1986 and 2016. Of the 254 participants, 116 were diagnosed with T2DM between T3 and T4, and were considered cases; the remaining 138 were controls. Linear mixed regression models were used to examine pre- and post-diagnostic changes in 25(OH)D concentrations, and logistic regression was used to examine associations between these concentrations and T2DM at each time-point. RESULTS: 25(OH)D concentrations at different time-points and the longitudinal change in concentrations differed between cases and controls, and by sex. For women, each 5-nmol/l increase in 25(OH)D concentrations was inversely associated with T2DM at T3 (odds-ratio, OR, 0.79), whereas for men, this same increase was positively associated with T2DM at T1 (OR 1.12). Cases experienced a significant decrease in pre-diagnostic 25(OH)D concentrations (p value < 0.01 for women, p value = 0.02 for men) and a significant increase in post-diagnostic 25(OH)D concentrations (p value < 0.01 for women, p value = 0.01 for men). As such, each 1-unit increase in month-specific z-score change between T1 and T3 was significantly inversely associated with T2DM (OR 0.51 for women, OR 0.52 for men), and each such increase between T3 and T5 was significantly positively associated with T2DM in women (OR 2.48). CONCLUSIONS: 25(OH)D concentrations seem to be affected by disease progression and type 2 diabetes diagnosis.

Associations between polymorphisms related to calcium metabolism and human height: the Tromsø Study.

A number of single nucleotide polymorphisms (SNPs) related to height have been detected. Calcium metabolism is important for the skeleton and accordingly also for adult height. Therefore, in the present study, nine SNPs related to the vitamin D receptor (VDR) gene and serum levels of 25-hydroxyvitamin D (25(OH)D), calcium, phosphate and parathyroid hormone (PTH) were related to height in 9471 subjects. Relation with height was evaluated with linear regression for trend across SNP genotypes with age and gender as covariates. After correcting for multiple testing, significant associations with height were found for two SNPs related to the VDR gene (rs1544410 (Bsml) and rs7975232 (Apal)), one SNP related to serum 25(OH)D (rs3829251 at the DHCR7/NADSYN1 gene), one SNP related to serum calcium (rs1459015 at the PTH gene) and one SNP related to serum phosphate (rs1697421 at the ALPL gene). For rs3829251, the mean differences in height between major and minor homozygotes were 1.5-2.0 cm (P < 0.01) and were seen in both genders and all age groups tested, whereas for the other SNPs, the differences were less than 1 cm. In conclusion, several SNPs related to calcium metabolism are associated with height, in particular rs3829251 at the DHCR7/NADSYN1 gene.

Effects of a 1-year supplementation with cholecalciferol on interleukin-6, tumor necrosis factor-alpha and insulin resistance in overweight and obese subjects.

Insufficient vitamin D status has been linked to autoimmune diseases, cancer and metabolic disorders, like obesity and insulin resistance. In vitro and animal studies suggest that vitamin D may play a crucial role in immune activation and inflammation. The relation between vitamin D and pro-inflammatory cytokines is not completely established. Furthermore, it is not known if the effect of vitamin D on entities of metabolic syndrome is mediated through its effect on cytokines or other biomarkers. The objectives of this study were to investigate if there is a relationship between vitamin D status and such pro-inflammatory cytokines as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and high sensitive C-reactive protein (hs-CRP) in patients with overweigh and obesity. We also proposed that the intervention with high dose of cholecalciferol may have effect on the cytokine levels and result in corresponding changes in the measures of insulin resistance (HOMA-IR and QUICKI). Serum levels of IL-6, TNF-α and hs-CRP were measured in 332 overweight and obese subjects who completed a 1-year randomised intervention with either 40,000 IU vitamin D (cholecalciferol) per week or 20,000 IU vitamin D per week, or placebo. We found significant associations between IL-6, TNF-α, vitamin D and insulin resistance indices at baseline. One year intervention with vitamin D decreased serum IL-6 levels; however hs-CRP levels were significantly increased. Neither measures of insulin resistance, nor TNF-α were influenced by a 1-year vitamin D supplementation.

Effect of vitamin D supplement on depression scores in people with low levels of serum 25-hydroxyvitamin D: nested case-control study and randomised clinical trial.

AIMS: To compare depressive symptoms in participants with low and high serum 25-hydroxyvitamin D (25(OH)D) levels and to examine whether supplementation with vitamin D(3) would improve symptoms in those with low serum 25(OH)D levels. METHOD: Participants with low 25(OH)D levels were randomised to either placebo or 40 000 IU vitamin D(3) per week for 6 months. Individuals with high serum 25(OH)D levels were used as nested controls. Depressive symptoms were evaluated with the Beck Depression Inventory, Hospital Anxiety and Depression Scale, Seasonal Pattern Assessment Scale and Montgomery-Åsberg Depression Rating Scale. The study was registered at ClinicalTrials.gov (NCT00960232). RESULTS: Participants with low 25(OH)D levels (n = 230) at baseline were more depressed (P<0.05) than participants with high 25(OH)D levels (n = 114). In the intervention study no significant effect of high-dose vitamin D was found on depressive symptom scores when compared with placebo. CONCLUSIONS: Low levels of serum 25(OH)D are associated with depressive symptoms, but no effect was found with vitamin D supplementation.

Association between headache and serum 25-hydroxyvitamin D: the Tromsø Study: Tromsø 6.

BACKGROUND: High prevalence of headache has been associated with high latitude, thus suggesting a relation with vitamin D. However, there are so far no reports on the association between serum 25-hydroxyvitamin D (25[OH]D) and headache. OBJECTIVE: To investigate the association between headache and serum 25(OH)D in a general population. METHODS: Cross-sectional study based on questionnaires from 11,614 persons who participated in the sixth survey of the Tromsø Study (Tromsø 6) carried out in 2007-2008. The data were stratified according to smoking status and analyzed with regard to migraine and non-migraine headache. Adjustments were done for age, body mass index (BMI), gender, season, chronic diseases, education, physical exercise, and alcohol consumption. RESULTS: Headache of non-migraine type was associated with low levels of serum 25(OH)D with an odds ratio (OR) of 1.20 (1.04-1.39) in the lowest quartile as compared to the highest serum 25(OH)D quartile. No significant association was found between migraine and serum 25(OH)D. CONCLUSION: Non-migraine headache was associated with low levels of serum 25(OH)D. Although adjustment were done for possible confounders, this finding may still reflect lifestyle rather than causality, and further studies are needed to investigate this. No association was found between serum 25(OH)D and migraine.