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.

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.

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).

Vitamin D Supplementation for Prevention of Type 2 Diabetes Mellitus: To D or Not to D?

CONTEXT: Over the last decade, vitamin D has emerged as a risk determinant for type 2 diabetes and vitamin D supplementation has been hypothesized as a potential intervention to lower diabetes risk. Recently, several trials have reported on the effect of vitamin D supplementation on diabetes prevention in people with prediabetes. EVIDENCE ACQUISITION: A comprehensive literature review was performed using PubMed, Embase, and ClinicalTrials.gov to identify: (1) recent meta-analyses of longitudinal observational studies that report on the association between blood 25-hydroxyvitamin D (25[OH]D) level and incident diabetes, and (2) clinical trials of adults with prediabetes that have reported on the effect of vitamin D supplementation on incident diabetes. EVIDENCE SYNTHESIS: Longitudinal observational studies report highly consistent associations between higher blood 25(OH)D levels and a lower risk of incident diabetes in diverse populations, including populations with prediabetes. Trials in persons with prediabetes show risk reduction in incident diabetes with vitamin D supplementation. In the 3 large trials that were specifically designed and conducted for the prevention of diabetes, vitamin D supplementation, when compared with placebo, reduced the risk of developing diabetes by 10% to 13% in persons with prediabetes not selected for vitamin D deficiency. CONCLUSIONS: Results from recent trials are congruent with a large body of evidence from observational studies indicating that vitamin D has a role in modulating diabetes risk. Participant-level meta-analysis of the 3 largest trials should provide a more refined estimate of risk reduction and identify patient populations that are likely to benefit the most from vitamin D supplementation.

Serum PTH is not a good marker for defining a threshold for vitamin D deficiency.

OBJECTIVE: In addition to its skeletal effects, vitamin D may also be important for health in general. It is uncertain what level of serum 25-hydroxyvitamin D (25(OH)D), marker of vitamin D status, is sufficient for these effects. With decreasing serum 25(OH)D levels there is an increase in serum PTH. The point at which this occurs has been considered as a threshold for vitamin D sufficiency. The thresholds found have varied widely and have mainly been based on observational studies. However, to truly establish a threshold for vitamin D effects, this has to be based on randomized controlled trials (RCTs). METHODS: The study included 2803 subjects from a general health survey, the Tromsø study, and pooled individual person data from five vitamin D intervention studies (n = 1544). Serum parathyroid hormone (PTH) and change in PTH after vitamin D supplementation were related to serum 25(OH)D levels in steps of 25 nmol/L (<24, 25-49, 50-74, 75-99, and >99 nmol/L). RESULTS: In the Tromsø study, in the females there was a gradual decrease in serum PTH with increasing serum 25(OH)D with no apparent plateau, whereas in the males the decrease in PTH in subjects with serum 25(OH)D >74 nmol/l was marginal. In pooled RCTs, there was a significant reduction in serum PTH by vitamin D supplementation regardless of baseline serum 25(OH)D level. CONCLUSIONS: The use of the serum PTH-25(OH)D relation from observational studies to determine a threshold for vitamin D sufficiency is highly questionable.

Four months vitamin D supplementation to vitamin D insufficient individuals does not improve muscular strength: A randomized controlled trial.

MAIN OBJECTIVE: The inconsistent results on the effects of vitamin D on muscle strength reported by intervention trials may partly be explained by inclusion of vitamin D sufficient individuals. The main objective was to study whether vitamin D supplementation will improve muscle strength in men and women with low serum vitamin D status, as measured by 25-hydroxyvitamin D (25(OH)D) at baseline. METHODS: 417 men and women aged 40-80 years were included and randomized to receive a loading dose of 100 000 IU (2500 ug) vitamin D3 followed by 20 000 IU (500 ug)/week, or placebo. Muscle strength was tested by dynamometers at baseline and after four months. RESULTS: Serum 25(OH)D levels increased from 32.6±11.1 nmol/l to 88.8±19.4 nmol/l (p<0.01) in the vitamin D group, while remaining low in the placebo group (baseline and final levels at 35.1±13.6 nmol/l and 30.7 ±9.7 nmol/l respectively). Muscle strength (hip flexion, biceps flexion, pectorals and handgrip strength) did not change in any of the groups. The results were the same in analyses stratified on sex, 25(OH)D above/below 25 nmol/L (10 ng/ml); smoking status; and BMI above/below 27 kg/m2. CONCLUSION: These data does not support vitamin D supplementation for improving muscle strength.

Alanine Aminotransferase and Body Composition in Obese Men and Women.

There is a known relationship between serum alanine aminotransferase (ALT) and obesity in humans, but the mechanism(s) are not clarified. This study investigated the associations between serum ALT and body composition in an overweight and obese population. The results are based on data from a previous randomized controlled trial treating obesity with vitamin D3. A sample of 448 overweight and obese individuals underwent dual-energy X-ray absorptiometry (DEXA) and measured serum ALT along with supplementary blood samples at study baseline. Body fat mass and lean mass indexes were calculated by dividing total body fat/lean weight (kg) by body height squared (kg/m2). ALT correlated with body mass index (BMI) in men but not women (r = 0.33, P < 0.0001 vs. r = 0.06, P = 0.29). In men, serum ALT correlated positively with fat mass index (r = 0.23, P = 0.004) and lean mass index (r = 0.32, P < 0.0001). In women, ALT correlated with lean mass index (r = 0.13, P = 0.031) but not fat mass index (r = 0.003, P = 0.96). In a multivariate model adjusted for age and fat mass index, a 1-unit increase in lean mass index associated with a 0.37 U/L higher ALT in the male subgroup (95% CI 0.024 to 0.040, P < 0.0001). In conclusion, serum ALT was associated with body fat mass index in men and with lean mass index in men and women in an overweight and obese population. The findings also demonstrate a gender difference in the role of fat.

Effects of vitamin D supplementation on bone turnover markers and other bone-related substances in subjects with vitamin D deficiency.

In observational studies, vitamin D deficiency is a risk factor for low bone density and future fractures, whereas a causal relation has been difficult to show in randomized controlled trials (RCTs). Similarly, vitamin D deficiency has been associated with increased bone turnover, but RCTs with vitamin D have not shown conclusive effects. This could be due to inclusion of vitamin D sufficient subjects and low vitamin D doses. In the present study 399 subjects with mean baseline serum 25-hydroxyvitamin D (25(OH)D) 34.0 nmol/L completed a four months intervention with vitamin D3 20,000 IU per week versus placebo. Mean serum 25(OH)D increased to 89.0 nmol/L in the vitamin D group and decreased slightly in the placebo group. A small, but significant, decrease in the bone formation marker procollagen of type 1 amino-terminal propeptide (P1NP) was seen in the vitamin D group as compared to the placebo group (mean delta P1NP -1.2 pg/mL and 1.5 ng/mL, respectively, P < 0.01). No significant effects were seen on serum carboxyl-terminal telopeptide of type 1 collagen (CTX-1), Dickkopf-1, sclerostin, tumor necrosis factor-alpha, osteoprotegerin, receptor activator of nuclear factor ĸB ligand, or leptin. Subgroup analyses on subjects with low baseline serum 25(OH)D did not yield additional, significant results. In subjects with high baseline serum parathyroid hormone (PTH) > 6.5 pmol/L and post-intervention decrease in PTH, the decrease in P1NP was more pronounced, they also exhibited significantly reduced serum CTX-1 and increased serum sclerostin. In conclusion, supplementation with vitamin D appears to suppress bone turnover, possibly mediated by PTH reduction. Our findings need to be confirmed in even larger cohorts with vitamin D insufficient subjects.

The Role of Vitamin D Binding Protein, Total and Free 25-Hydroxyvitamin D in Diabetes.

Vitamin D is important for bone health, but may also have extra-skeletal effects. Vitamin D and its binding protein DBP have immunological effects and may therefore be important in the development of type 1 diabetes (T1DM), and low serum levels of 25-hydroxyvitamin D (25(OH)D) are associated with later development of type 2 diabetes (T2DM). However, it has so far been difficult to convincingly show an effect of vitamin D supplementation on prevention or treatment of diabetes. The serum level of 25(OH)D has traditionally been used as a marker of a subject's vitamin D status. This measurement includes both 25(OH)D bound to DBP and albumin as well as the free from of 25(OH)D. However, according to the free hormone hypothesis, the free form is the biologically active. Previously the free form of 25(OH)D had to be calculated based on measurements of 25(OH)D, DBP, and albumin, but recently a method for direct measurement of free 25(OH)D has become commercially available. This is important in clinical conditions where the amount of DBP is affected, and has caused a renewed interest in which vitamin D metabolite to measure in clinical situations. In the present review the relations between DBP, total and free 25(OH)D in T1DM and T2DM are described.

Vitamin D supplementation has no effect on cognitive performance after four months in mid-aged and older subjects.

BACKGROUND: Low serum 25-hydroxyvitamin D (25(OH)D) levels are associated with impaired cognitive function, but the effect of vitamin D supplementation on cognitive function is uncertain. METHODS: 422 subjects were included in a randomized controlled trial with vitamin D (cholecalciferol) 100,000 IU given as a bolus dose followed by 20,000 IU per week versus placebo for four months. Cognitive function was evaluated with verbal recall test, coding test and tapping test. RESULTS: 374 subjects (mean age 52 years, 198 males) had complete cognitive tests both at baseline and at end of study. Mean baseline serum 25(OH)D level was 34 nmol/L. At baseline there were no significant associations between serum 25(OH)D and the three separate cognitive tests. At the end of the study mean serum 25(OH)D levels were 89 nmol/L and 31 nmol/L in the vitamin D and placebo groups, respectively. At the end of the study, there were no statistically significant differences between the two groups regarding change in the cognitive test scores. Nor did sub-group analyses based on gender, age, baseline serum 25(OH)D and cognitive test scores reveal significant differences between the two groups at the end of the study. CONCLUSIONS: Vitamin D supplementation did not improve cognitive function during a four months intervention in mid-aged and older subjects. TRIAL REGISTRATION: ClinicalTrials.govNCT02750293.

No improvement in depressive symptoms by vitamin D supplementation: results from a randomised controlled trial.

In observational studies, vitamin D deficiency is associated with depressive symptoms. However, randomised controlled trials (RCT) with vitamin D supplementation have not been conclusive. In the present study 206 subjects were randomised to vitamin D (100 000 IU (2500 µg) as a bolus dose followed by 20 000 IU (500 µg) per week) and 202 to placebo. The Beck Depression Inventory-II (BDI-II) was filled in at baseline and after 4 months at the end of the study. At baseline the mean age was 51·4 and 52·5 years and mean serum 25-hydroxyvitamin D (25(OH)D) 32·5 and 35·1 nmol/l in the vitamin D and placebo groups, respectively. Among the 408 subjects, 193 had a BDI-II score >4, and forty-five had a score >13. Twenty-three subjects were using anti-depressant or mood-stabilising drugs. At the end of the study, there were no significant differences in Δ BDI-II score (score at the end of the study minus score at baseline), regardless of analysing all subjects, subjects with or without psycopharmaca, or if performing subgroup analyses based on baseline and final serum 25(OH)D levels combined with categories of baseline BDI-II scores >4 or >13. In conclusion, we have not been able to demonstrate any significant effect of vitamin D supplementation on depressive symptoms. However, few of our subjects were clinically depressed. Future RCT should include subjects with more severe vitamin D deficiency as well as more depressed subjects than in our study. In such a setting vitamin D may probably be more relevant as an augmenter of standard antidepressant medication/treatment.

Rationale and Plan for Vitamin D Food Fortification: A Review and Guidance Paper.

Vitamin D deficiency can lead to musculoskeletal diseases such as rickets and osteomalacia, but vitamin D supplementation may also prevent extraskeletal diseases such as respiratory tract infections, asthma exacerbations, pregnancy complications and premature deaths. Vitamin D has a unique metabolism as it is mainly obtained through synthesis in the skin under the influence of sunlight (i.e., ultraviolet-B radiation) whereas intake by nutrition traditionally plays a relatively minor role. Dietary guidelines for vitamin D are based on a consensus that serum 25-hydroxyvitamin D (25[OH]D) concentrations are used to assess vitamin D status, with the recommended target concentrations ranging from ≥25 to ≥50 nmol/L (≥10-≥20 ng/mL), corresponding to a daily vitamin D intake of 10 to 20 µg (400-800 international units). Most populations fail to meet these recommended dietary vitamin D requirements. In Europe, 25(OH)D concentrations <30 nmol/L (12 ng/mL) and <50 nmol/L (20 ng/mL) are present in 13.0 and 40.4% of the general population, respectively. This substantial gap between officially recommended dietary reference intakes for vitamin D and the high prevalence of vitamin D deficiency in the general population requires action from health authorities. Promotion of a healthier lifestyle with more outdoor activities and optimal nutrition are definitely warranted but will not erase vitamin D deficiency and must, in the case of sunlight exposure, be well balanced with regard to potential adverse effects such as skin cancer. Intake of vitamin D supplements is limited by relatively poor adherence (in particular in individuals with low-socioeconomic status) and potential for overdosing. Systematic vitamin D food fortification is, however, an effective approach to improve vitamin D status in the general population, and this has already been introduced by countries such as the US, Canada, India, and Finland. Recent advances in our knowledge on the safety of vitamin D treatment, the dose-response relationship of vitamin D intake and 25(OH)D levels, as well as data on the effectiveness of vitamin D fortification in countries such as Finland provide a solid basis to introduce and modify vitamin D food fortification in order to improve public health with this likewise cost-effective approach.

Effects of vitamin D supplementation on markers for cardiovascular disease and type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials.

Background: Evidence from randomized controlled trials (RCTs) for the causal role of vitamin D on noncommunicable disease outcomes is inconclusive. Objective: The aim of this study was to investigate whether there are beneficial or harmful effects of cholecalciferol (vitamin D3) supplementation according to subgroups of remeasured serum 25-hydroxyvitamin D [25(OH)D] on cardiovascular and glucometabolic surrogate markers with the use of individual participant data (IPD) meta-analysis of RCTs. Design: Twelve RCTs (16 wk to 1 y of follow-up) were included. For standardization, 25(OH)D concentrations for all participants (n = 2994) at baseline and postintervention were re-measured in bio-banked serum samples with the use of a certified liquid chromatography-tandem mass spectrometry method traceable to a reference measurement procedure. IPD meta-analyses were performed according to subgroups of remeasured 25(OH)D. Main outcomes were blood pressure and glycated hemoglobin (HbA1c). Secondary outcomes were LDL, HDL, and total cholesterol and triglycerides; parathyroid hormone (PTH); fasting glucose, insulin, and C-peptide; and 2-h glucose. In secondary analyses, other potential effect modifiers were studied. Results: Remeasurement of 25(OH)D resulted in a lower mean 25(OH)D concentration in 10 of 12 RCTs. Vitamin D supplementation had no effect on the main outcomes of blood pressure and HbA1c. Supplementation resulted in 10-20% lower PTH concentrations, irrespective of the 25(OH)D subgroups. The subgroup analyses according to achieved 25(OH)D concentrations showed a significant decrease in LDL-cholesterol concentrations after vitamin D supplementation in 25(OH)D subgroups with <75, <100, and <125 nmol of -0.10 mmol/L (95% CI: -0.20, -0.00 mmol/L), -0.10 mmol/L (95% CI: -0.18, -0.02 mmol/L), and -0.07 mmol/L (95% CI: -0.14, -0.00 mmol/L), respectively. Patient features that modified the treatment effect could not be identified. Conclusions: For the main outcomes of blood pressure and HbA1c, the data support no benefit for vitamin D supplementation. For the secondary outcomes, in addition to its effect on PTH, we observed indications for a beneficial effect of vitamin D supplementation only on LDL cholesterol, which warrants further investigation. This trial was registered at www.clinicaltrials.gov as NCT02551835.

Vitamin D supplementation does not improve CVD risk factors in vitamin D-insufficient subjects.

OBJECTIVE: Low serum 25(OH)D levels are associated with cardiovascular disease (CVD) and some of its risk factors. However, in interventional studies, the effects of vitamin D supplementation have been uncertain, possibly due to inclusion of vitamin D-sufficient subjects. Our aim was therefore to examine effects of vitamin D supplementation on CVD risk factors in vitamin D-insufficient subjects. DESIGN: Double-blinded randomized controlled trial. METHODS: A 4-month interventional study with high-dose vitamin D (100,000 IU loading dose, followed by 20,000 IU/week) or placebo with measurements of blood pressure, lipids (total-, LDL- and HDL-cholesterol, triglycerides, apolipoproteins A1 and B), and glucose metabolism parameters (blood glucose, HbA1c, serum human receptors for advanced glycation end products (sRAGE), insulin, C-peptide and HOMA-IR). RESULTS: A total of 422 subjects with mean serum 25(OH)D level 34 nmol/L were included, with 411 subjects completing the study. Serum 25(OH)D levels increased with 56 nmol/L and decreased with 4 nmol/L in the vitamin D and placebo group, respectively. We found no statistically significant differences between the two groups in any of the measured CVD risk factors, except for a minor increase in sRAGE in the vitamin D group. Stratified analyses of subjects with low baseline serum 25(OH)D levels alone, or combined with blood pressure, lipid and HOMA-IR values above the median for the cohort, did not skew the results in favour of vitamin D supplementation. CONCLUSION: Supplementation with vitamin D in subjects with baseline vitamin D insufficiency does not improve CVD risk factor profile.

Exploring the association between serum 25-hydroxyvitamin D and serum lipids-more than confounding?

BACKGROUND/OBJECTIVES: In observational, but not interventional, studies there are strong associations between serum 25-hydroxyvitamin D (25(OH)D) and serum lipids. The purpose of the present study was to examine potential causes of this association. SUBJECTS/METHODS: A total of 17,411 subjects participating in the seventh survey of the Tromsø Study were included in the cross-sectional study; 5384 subjects who participated in both the sixth and seventh survey were included in the longitudinal study; 2365 subjects who participated in both the fourth and seventh survey were included in the genetic study; and 479 subjects with impaired glucose tolerance were included in the vitamin D binding protein (DBP) analyses. RESULTS: For serum 25(OH)D, there were strong and positive associations with LDL-, HDL-, and total-cholesterol, and a negative association with triglycerides that remained after adjustment for gender, age, BMI, diet, supplements, and lifestyle factors. These associations were seen in winter as well as summer. Except for serum cholesterol, change of season for blood sampling did not affect lipid levels. However, when analyzing separately, subjects with low or no intake of vitamin D supplements, fish oil and fat fish, only the association between 25(OH)D and HDL-cholesterol remained significant. Serum DBP or single-nucleotide polymorphisms related to 25(OH)D had no relation to lipid levels. CONCLUSIONS: The associations between 25(OH)D and lipids (except for HDL-cholesterol) can be explained by known confounding factors. However, for HDL-cholesterol, the cause of the association with 25(OH)D still remains unknown.

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.

RCTS are the only appropriate way to demonstrate the role of vitamin D in health.

Despite thousands of vitamin D studies published, including hundreds of reviews and meta-analyses, it is still uncertain if supplementation with vitamin D will have positive health effects, except for the skeleton. This cannot be answered by doing more observational studies as it is impossible to control for confounding factors and reverse causality. The only way to firmly prove positive vitamin D effects is by doing the properly designed randomized controlled trials (RCTs). However, it has been difficult to show the expected positive effects by vitamin D supplementation in RCTs, which may indicate that the effects, if present must be small. On the other hand, results from Mendelian randomization studies have shown promising results at least for mortality and multiple sclerosis. In the near future, results from several large RCTs with hard endpoints will be available. If these show positive results, the main question on vitamin D and health is answered. If they turn out negative, they will be criticized for having included subjects without vitamin D deficiency, and some studies might not have used an optimal dosing regimen. New and better-designed RCTs will then be needed, but will be very hard to perform.

Vitamin D Stored in Fat Tissue During a 5-Year Intervention Affects Serum 25-Hydroxyvitamin D Levels the Following Year.

Context: Vitamin D and 25-hydroxyvitamin D [25(OH)D] are stored in adipose tissue, but the clinical relevance is uncertain. Objective: To evaluate changes in serum 25(OH)D and adipose tissue vitamin D levels after stopping vitamin D supplementation. Design: A prospective, double-blind cohort follow-up study. Setting: Clinical Research Unit at University Hospital of North Norway. Patients: Seventy-six subjects were included after participation in a 3- to 5-year prevention of type 2 diabetes study and were administered 20,000 IU of vitamin D or placebo per week. Intervention: During the 12-month follow-up period, blood samples were drawn at the beginning and after 1, 3, 6, 9, and 12 months. Fat biopsies were taken at the start and end. Main Outcome Measures: Changes in 25(OH)D level in serum and 25(OH)D and vitamin D levels in adipose tissue. Results: Forty-one of 42 subjects who were given vitamin D and 33 of 34 subjects who were given placebo completed the study. At the inclusion, mean serum 25(OH)D levels were 122 and 71 nmol/L in the vitamin D and placebo groups, respectively. Serum 25(OH)D levels were significantly higher in the vitamin D group than in the placebo group throughout and were 84.5 and 73.1 nmol/L, respectively, after 12 months. In the vitamin D group, adipose tissue vitamin D levels decreased by 52% over 12 months. Conclusion: Vitamin D and 25(OH)D stored in adipose tissue after 3 to 5 years of vitamin D supplementation may have a clinically relevant effect on serum 25(OH)D level the following year.