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.

Bone mineral density is close to normal for age in long-term lymphoma survivors treated with high-dose therapy with autologous stem cell transplantation.

BACKGROUND: Few studies have assessed bone health in lymphoma survivors treated with high-dose therapy with autologous stem cell transplantation (HDT-ASCT). Therefore, we aimed to assess bone mineral density (BMD) at six different skeletal sites and to investigate associations between clinical factors and BMD in these survivors. MATERIAL AND METHODS: Eligible lymphoma survivors were aged ≥18 years at diagnosis and at HDT-ASCT given between 1987 and 2008. Participants responded to questionnaires, blood samples were drawn, and a dual energy X-ray absorptiometry (DXA) was performed. Mean Z-score was applied for assessment of BMD in relation to age. Prevalence of Z-scores ≥-1, between -1 and -2, and ≤-2 is reported for each measurement site and for the lumbar spine, femoral neck, and hip in combination. Likewise, T-scores were applied to assess the prevalence of normal BMD (≥-1), osteopenia (between -1 and -2.5), and osteoporosis (≤-2.5). RESULTS: We included 228 lymphoma survivors, of whom 62% were males. The median age at survey was 56 years, and median observation time from HDT-ASCT was eight years. Among males, Z-scores were lower at the left femoral neck and higher at the ultra-distal (UD) radius and whole body compared to the Lunar reference database. In females, Z-scores were lower at UD radius and one-third (33%) radius and higher at the whole body. Using a classification based on Z-scores at the lumbar spine, femoral neck, and hip in combination, 25% of males and 16% of females had Z-scores <-1 and >-2, while 8% and 6% had Z-scores ≤-2. According to T-scores, 35% of males and 41% of females had osteopenia, while 8% and 13% had osteoporosis, respectively. CONCLUSION: BMD was close to normal for age in this population of long-term lymphoma survivors treated with HDT-ASCT.

Prevention of urinary tract infections with vitamin D supplementation 20,000 IU per week for five years. Results from an RCT including 511 subjects.

BACKGROUND: In observational studies vitamin D deficiency is associated with increased risk of infections, whereas the effect of vitamin D supplementation in randomized controlled trials is non-conclusive. METHODS: Five hundred and eleven subjects with prediabetes were randomized to vitamin D3 (20,000 IU per week) versus placebo for five years. Every sixth month, a questionnaire on respiratory tract infections (RTI) (common cold, bronchitis, influenza) and urinary tract infection (UTI) was filled in. RESULTS: Mean baseline serum 25-hydroxyvitamin D (25(OH)D) level was 60 nmol/L. Two hundred and fifty-six subjects received vitamin D and 255 placebo. One hundred and sixteen subjects in the vitamin D and 111 in the placebo group completed the five-year study. Eighteen subjects in the vitamin D group and 34 subjects in the placebo group reported UTI during the study (p < 0.02), whereas no significant differences were seen for RTI. The effect on UTI was most pronounced in males. The effect of vitamin D on UTI was unrelated to baseline serum 25(OH)D level. CONCLUSION: Supplementation with vitamin D might prevent UTI, but confirmatory studies are needed.

Vitamin D 20,000 IU per Week for Five Years Does Not Prevent Progression From Prediabetes to Diabetes.

CONTEXT: Vitamin D deficiency is associated with insulin resistance and risk of future diabetes. OBJECTIVE: The objective of the study was to test whether supplementation with vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes mellitus (T2DM). DESIGN: This was a randomized controlled trial performed in 2008 through 2015. SETTING: The study was conducted at the clinical research unit at a teaching hospital. PATIENTS: Five hundred eleven subjects (mean age 62 y, 314 males) with prediabetes diagnosed with an oral glucose tolerance test as part of the Tromsø Study 2007­2008 were included. A total of 256 were randomized to vitamin D and 255 to placebo. Twenty-nine subjects in the vitamin D and 24 in the placebo group withdrew because of adverse events. INTERVENTIONS: Interventions included vitamin D (cholecalciferol) 20 000 IU/wk vs placebo for 5 years. Annual oral glucose tolerance tests were performed. MAIN OUTCOME MEASURE: Progression to T2DM was the main outcome measure. Secondary outcomes were change in glucose levels, insulin resistance, serum lipids, and blood pressure. RESULTS: The mean baseline serum 25-hydroxyvitamin D level was 60 nmol/L (24 ng/mL). One hundred three in the vitamin D and 112 in the placebo group developed T2DM (hazard risk 0.90; 95% confidence interval 0.69­1.18, Cox regression, P = .45, intention to treat analysis). No consistent significant effects on the other outcomes were seen. Subgroup analyses in subjects with low baseline 25-hydroxyvitamin D yielded similar results. No serious side effects related to the intervention were recorded. CONCLUSIONS: In subjects without vitamin D deficiency, vitamin D supplementation is unlikely to prevent progression from prediabetes to diabetes. Very large studies with inclusion of vitamin D-deficient subjects will probably be needed to show such a putative effect. This study tested if supplementation with vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes (T2DM).

No effect of high-dose vitamin D supplementation on glycemic status or cardiovascular risk factors in subjects with prediabetes.

OBJECTIVE: In observational studies, low serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with insulin resistance and other risk factors for cardiovascular disease. RESEARCH DESIGN AND METHODS: We present 1-year data from an ongoing 5-year trial in 511 individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) randomly assigned to 20,000 IU/week vitamin D3 or placebo. An oral glucose tolerance test was performed at baseline and after 1 year. RESULTS: Mean baseline serum 25(OH)D was 59.9 nmol/L and 61.1 nmol/L in the vitamin D and placebo groups, respectively, and increased by 45.8 nmol/L and 3.4 nmol/L, respectively. With adjustment for baseline concentrations, no differences in measures of glucose metabolism, insulin secretion or sensitivity, blood pressure, or hs-CRP were found after 1 year. There was a slight, but significant decrease in total and LDL cholesterol in the vitamin D group compared with the placebo group, but as there was also a decrease in HDL cholesterol, the change in the total/HDL cholesterol ratio did not differ significantly. Only analyzing subjects with 25(OH)D <50 nmol/L did not change the results. CONCLUSIONS: This study shows that vitamin D supplementation does not improve glycemic indices, blood pressure, or lipid status in subjects with IFG and/or IGT.

The serum 25-hydroxyvitamin D response to vitamin D supplementation is related to genetic factors, BMI, and baseline levels.

OBJECTIVE: The serum 25-hydroxyvitamin D (25(OH)D) level is not only dependent on vitamin D intake and production in the skin but also dependent on genetic factors. Thus, in large genome-wide association studies, it has been shown that single nucleotide polymorphisms (SNPs) in the vitamin D binding protein (DBP), as well as in enzymes related to activation or degradation of vitamin D and its metabolites, are as important for the serum 25(OH)D level as the effect of season. How these SNPs affect the serum 25(OH)D response to vitamin D supplementation is uncertain. DESIGN AND METHODS: Data were pooled from three randomized controlled trials where 40, 000 IU vitamin D/week was given for 6 months. Serum 25(OH)D was measured before and at the end of the intervention, and the subjects were genotyped for SNPs related to the serum 25(OH)D level. RESULTS: Baseline 25(OH)D levels were significantly related to SNPs in the DBP and CYP2R1 genes. Those with SNPs associated with the lowest baseline 25(OH)D levels also had the smallest increase (delta) after supplementation. Those with the lowest baseline serum 25(OH)D (without regard to genotypes) had the highest increase (delta) after supplementation. Subjects with high BMI had lowest baseline 25(OH)D levels and also the smallest increase (delta) after supplementation. CONCLUSIONS: The serum 25(OH)D response to supplementation depends on genes, baseline level, and BMI. However, whether this is clinically important or not depends on the therapeutic window of vitamin D, an issue that is still not settled.

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.

Plasma profile of microRNA after supplementation with high doses of vitamin D3 for 12 months.

BACKGROUND: Recently a large number of short non-coding-RNAs (microRNAs, (miRNA)) have been identified. These miRNAs act as post-transcriptional regulators where they generally have an inhibitory function. miRNAs are present in all human cells, and they are also detected in serum or plasma. The miRNAs have a broad range of actions, and their biogenesis must therefore be under tight control. One putative regulator of miRNA biogenesis or miRNA level could be vitamin D, an ancient hormone with effects on cell growth and differentiation, apoptosis and the immune system. In our study miRNA were reversed transcribed in total RNA isolated from plasma and analyzed by quantitative real-time PCR (qPCR) using the miRCURY LNA Universal RT microRNA PCR system (Exiqon). In 10 pilot subjects 136 miRNAs were detected in one or more plasma samples drawn at baseline and after 12 months of vitamin D supplementation. The twelve miRNAs that showed the greatest change in expression in these pilots were further analyzed by RT-qPCR of RNA from baseline and 12 months plasma samples in 40 subjects given high dose vitamin D(3) (20.000-40.000 IU per week) and 37 subjects given placebo. RESULTS: At baseline there was a significant and positive correlation between serum 25-hydroxyvitamin D and miR-532-3p expression (r = 0.24, P = 0.04). The change in expression of miR-221 from baseline to 12 months (ddCp value) was also significantly different between the vitamin D and placebo group (P =0.04), mainly due to a change in the placebo group. CONCLUSIONS: We have not been able to demonstrate a consistent effect of vitamin D supplementation on the expression profile of miRNA in plasma. However, further studies are needed as this approach might potentially throw light on unknown aspects of vitamin D physiology.

The associations of age, lifestyle factors and chronic disease with testosterone in men: the Tromsø Study.

OBJECTIVE: To study whether lifestyle factors and/or chronic disease are associated with the age-related decline of total and free testosterone in men, or if these factors might be associated with the variation of total and free testosterone but not with their age-related decline. DESIGN: A population-based, cross-sectional study was used. METHODS: Total testosterone and sex hormone binding globulin (SHBG) levels were analyzed and free testosterone levels were calculated in 1563 men participating in the Tromsø study in 1994/1995. Anthropometric characteristics were also measured and two standardized questionnaires completed, including lifestyle factors and medical history. The data were analyzed with multiple linear regression analysis of covariance, and logistic regression. RESULTS: Total and free testosterone were inversely associated (P=0.001 and P<0.001), while SHBG was positively associated (P<0.001) with age. Body mass index (BMI) was inversely associated with total (P<0.001) and free (P=0.016) testosterone and SHBG (P<0.001). Both total and free testosterone were positively associated with tobacco consumption (P<0.001 and P=0.004) and total testosterone was positively associated with coffee consumption (P<0.001). SHBG was positively associated with smoking (P=0.004) and coffee consumption (P<0.001). Men who reported having had a stroke or having a cancer diagnosis had lower levels of total testosterone (P<0.001 and P<0.01) and free testosterone (P<0.01). CONCLUSIONS: BMI and smoking are independent contributors to the variation of total and free testosterone and SHBG levels, and coffee consumption to the variation of total testosterone and SHBG. Thus, lifestyle factors can have a direct effect on circulating levels of free endogenous sex hormones and to total levels due to the effect on SHBG levels.