The association of 25-hydroxyvitamin D3 and D2 with behavioural problems in childhood

Background

Higher serum concentrations of 25-hydroxyvitamin D (25(OH)D), an indicator of vitamin D synthesis and intake, have been associated with better mental health and cognitive function. Concentrations of 1,25-dihydroxyvitamin D₃ (the active vitamin D₃ metabolite) have been associated with openness and extrovert behaviour, but 25(OH)D concentrations have not been associated with behavioural problems in humans.

Methods

We investigated the prospective association between the different forms of 25(OH)D - 25(OH)D₃ and 25(OH)D₂– and childhood behavioural problems in Avon Longitudinal Study of Parents and Children (ALSPAC). Serum 25(OH)D₃ and 25(OH)D₂ concentrations were assessed at mean age 9.9 years. Incident behavioural problems were assessed with Strengths and Difficulties Questionnaire (SDQ; emotional symptoms, conduct problems, hyperactivity-inattention problems, peer relationship problems and pro-social behaviour subscales and total difficulties score) at mean age 11.7. Sample sizes varied between 2413-2666 depending on the outcome.

Results

Higher 25(OH)D₃ concentrations were weakly associated with lower risk of prosocial problems (fully adjusted odds ratio: OR (95% confidence interval: CI) 0.85 (0.74, 0.98)). Serum 25(OH)D₃ or 25(OH)D₂ concentrations were not associated with other subscales of SDQ or total difficulties score after adjusting for concfounders and other measured analytes related to vitamin D.

Conclusions

Our findings do not support the hypothesis that 25-hydroxyvitamin D status in childhood has important influences on behavioural traits in humans.     

Case-control study of vitamin D, dickkopf homolog 1 (DKK1) gene methylation, VDR gene polymorphism and the risk of colon adenoma in African Americans

Background

There are sparse data on genetic, epigenetic and vitamin D exposure in African Americans (AA) with colon polyp. Consequently, we evaluated serum 25(OH) D levels, vitamin D receptor (VDR) polymorphisms and the methylation status of the tumor suppressor gene dickkopf homolog 1 (DKK1) as risk factors for colon polyp in this population.

Methods

The case-control study consisted of 93 patients with colon polyp (cases) and 187 healthy individuals (controls) at Howard University Hospital. Serum levels of 25(OH)D (including D3, D2, and total) were measured by liquid chromatography-mass spectrometry. DNA analysis focused on 49 single nucleotide polymorphisms (SNPs) in the VDR gene. Promoter methylation analysis of DKK1 was also performed. The resulting data were processed in unadjusted and multivariable logistic regression analyses.

Results

Cases and controls differed in vitamin D status (D₃<50 nmol/L: Median of 35.5 in cases vs. 36.8 in controls nmol/L; P = 0.05). Low levels of 25(OH)D₃ (<50 nmol/L) were observed in 86% of cases and 68% of controls and it was associated with higher risks of colon polyp (odds ratio of 2.7, 95% confidence interval 1.3–3.4). The SNP analysis showed no association between 46 VDR polymorphisms and colon polyp. The promoter of the DKK1 gene was unmethylated in 96% of the samples.

Conclusion

We found an inverse association between serum 25(OH)D₃ and colon polyp in AAs. VDR SNPs and DKK1 methylation were not associated with colon polyp. Vitamin D levels may in part explain the higher incidence of polyp in AAs.     

A genetic validation study reveals a role of vitamin D metabolism in the response to interferon-alfa-based therapy of chronic hepatitis C

Background

To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C.

Methodology/Principal Findings

Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D₃ (25[OH]D₃) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D₃<20 ng/mL) during all seasons, but 25(OH)D₃ serum levels were not associated with treatment outcome.

Conclusions/Significance

Our study suggests a role of bioactive vitamin D (1,25[OH]₂D₃, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D₃ is not a suitable predictor of treatment outcome.     

Interactions between plasma levels of 25-hydroxyvitamin D, insulin-like growth factor (IGF)-1 and C-peptide with risk of colorectal cancer

Background

Vitamin D status and levels of insulin-like growth factor (IGF)-1 and C-peptide have been implicated in colorectal carcinogenesis. However, in contrast to vitamin D IGF-1 is not an easily modifiable risk factor.

Methods

Combining data from the Health Professionals Follow up Study (HPFS) and the Nurses'' Health Study cohort (NHS) additive and multiplicative interactions were examined between plasma 25-hydroxyvitamin D (25(OH)D) and IGF-1, IGFBP-3 as well as C-peptide levels in 499 cases and 992 matched controls. For the various analytes, being high or low was based on being either above (or equal) or below the medians, respectively.

Results

Compared to participants with high 25(OH)D and low IGF-1/IGFBP-3 ratio (reference group), participants with a high IGF-1/IGFBP-3 ratio were at elevated risk of colorectal cancer when 25(OH)D was low (odds ratio (OR): 2.05 (95% CI: 1.43 to 2.92), but not when 25(OH)D was high (OR:1.20 (95% CI: 0.84 to 1.71, p(interaction): additive  = 0.06, multiplicative  = 0.25). Similarly, compared to participants with high 25(OH)D and low molar IGF-1/IGFBP-3 ratio and low C-peptide levels (reference group), participants with a combination of either high IGF-1/IGFBP-3 ratio or high C-peptide were at elevated risk for colorectal cancer when 25(OH)D was low (OR = 1.90, 95% CI: 1.22 to 2.94) but not when 25(OH)D was high (OR = 1.15, 95% CI: 0.74 to 1.77, p(interaction): additive = 0.004; multiplicative  = 0.04).

Conclusion

The results from this study suggest that improving vitamin D status may help lower risk of colorectal cancer associated with higher IGF-1/IGFBP-3 ratio or C-peptide levels.     

Vitamin D status and bone and connective tissue turnover in brown bears (Ursus arctos) during hibernation and the active state

Background

Extended physical inactivity causes disuse osteoporosis in humans. In contrast, brown bears (Ursus arctos) are highly immobilised for half of the year during hibernation without signs of bone loss and therefore may serve as a model for prevention of osteoporosis.

Aim

To study 25-hydroxy-vitamin D (25OHD) levels and bone turnover markers in brown bears during the hibernating state in winter and during the active state in summer. We measured vitamin D subtypes (D₂ and D₃), calcitropic hormones (parathyroid hormone [PTH], 1,25-dihydroxy-vitamin D [1,25(OH)₂D]) and bone turnover parameters (osteocalcin, ICTP, CTX-I), PTH, serum calcium and PIIINP.

Material and Methods

We drew blood from seven immobilised wild brown bears during hibernation in February and in the same bears while active in June.

Results

Serum 25-hydroxy-cholecalciferol (25OHD₃) was significantly higher in the summer than in the winter (22.8±4.6 vs. 8.8±2.1 nmol/l, two tailed p - 2p = 0.02), whereas 25-hydroxy-ergocalciferol (25OHD₂) was higher in winter (54.2±8.3 vs. 18.7±1.7 nmol/l, 2p<0.01). Total serum calcium and PTH levels did not differ between winter and summer. Activated 1,25(OH)₂D demonstrated a statistically insignificant trend towards higher summer levels. Osteocalcin levels were higher in summer than winter, whereas other markers of bone turnover (ICTP and CTX-I) were unchanged. Serum PIIINP, which is a marker of connective tissue and to some degree muscle turnover, was significantly higher during summer than during winter.

Conclusions

Dramatic changes were documented in the vitamin D₃/D₂ ratio and in markers of bone and connective tissue turnover in brown bears between hibernation and the active state. Because hibernating brown bears do not develop disuse osteoporosis, despite extensive physical inactivity we suggest that they may serve as a model for the prevention of this disease.     

Prediagnostic plasma vitamin D metabolites and mortality among patients with prostate cancer

Background

Laboratory evidence suggests that vitamin D might influence prostate cancer prognosis.

Methodology/Principal Findings

We examined the associations between prediagnostic plasma levels of 25(OH)vitamin D [25(OH)D] and 1,25(OH)₂vitamin D [1,25(OH)₂D] and mortality among 1822 participants of the Health Professionals Follow-up Study and Physicians'' Health Study who were diagnosed with prostate cancer. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of total mortality (n = 595) and lethal prostate cancer (death from prostate cancer or development of bone metastases; n = 202). In models adjusted for age at diagnosis, BMI, physical activity, and smoking, we observed a HR of 1.22 (95% CI: 0.97, 1.54) for total mortality, comparing men in the lowest to the highest quartile of 25(OH)D. There was no association between 1,25(OH)₂D and total mortality. Men with the lowest 25(OH)D quartile were more likely to die of their cancer (HR: 1.59; 95% CI: 1.06, 2.39) compared to those in the highest quartile (P_trend = 0.006). This association was largely explained by the association between low 25(OH)D levels and advanced cancer stage and higher Gleason score, suggesting that these variables may mediate the influence of 25(OH)D on prognosis. The association also tended to be stronger among patients with samples collected within five years of cancer diagnosis. 1,25(OH)₂D levels were not associated with lethal prostate cancer.

Conclusions/Significance

Although potential bias of less advanced disease due to more screening activity among men with high 25(OH)D levels cannot be ruled out, higher prediagnostic plasma 25(OH)D might be associated with improved prostate cancer prognosis.     

Serum 25-hydroxyvitamin D and risk of lung cancer in male smokers: a nested case-control study

Background

A role for vitamin D in cancer risk reduction has been hypothesized, but few data exist for lung cancer. We investigated the relationship between vitamin D status, using circulating 25-hydroxyvitamin D [25(OH)D], and lung cancer risk in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers.

Methods

Lung cancer cases (n = 500) were randomly selected based on month of blood collection, and 500 controls were matched to them based on age and blood collection date. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate-adjusted conditional logistic regression. To account for seasonal variation in 25(OH)D concentrations, season-specific and season-standardized quintiles of 25(OH)D were examined, and models were also stratified on season of blood collection (darker season = November–April and sunnier season = May–October). Pre-determined, clinically-defined cutpoints for 25(OH)D and 25(OH)D as a continuous measure were also examined.

Results

Overall, 25(OH)D was not associated with lung cancer. Risks were 1.08 (95% CI 0.67–1.75) and 0.83 (95% CI 0.53–1.31) in the highest vs. lowest season-specific and season-standardized quintiles of 25(OH)D, respectively, and 0.91 (95% CI 0.48–1.72) for the ≥75 vs. <25 nmol/L clinical categories. Inverse associations were, however, suggested for subjects with blood collections from November–April, with ORs of 0.77 (95% CI 0.41–1.45, p-trend = 0.05) and 0.65 (95% CI 0.37–1.14, p-trend = 0.07) in the highest vs. lowest season-specific and season-standardized quintiles of 25(OH)D, respectively, and 0.61 (95% CI 0.24–1.52, p-trend = 0.01) for ≥75 vs. <25 nmol/L. We also found 11% lower risk for a 10 nmol/L increase in 25(OH)D in the darker season based on the continuous measure (OR = 0.89, 95% CI 0.81–0.98, p = 0.02).

Conclusion

In this prospective study of male smokers, circulating 25(OH)D was not associated with lung cancer risk overall, although inverse associations were suggested among those whose blood was drawn during darker months.     

Vitamin D3 deficiency differentially affects functional and disease outcomes in the G93A mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by motor neuron death in the central nervous system. Vitamin D supplementation increases antioxidant activity, reduces inflammation and improves motor neuron survival. We have previously demonstrated that vitamin D₃ supplementation at 10× the adequate intake improves functional outcomes in a mouse model of ALS.

Objective

To determine whether vitamin D deficiency influences functional and disease outcomes in a mouse model of ALS.

Methods

At age 25 d, 102 G93A mice (56 M, 46 F) were divided into two vitamin D₃ groups: 1) adequate (AI; 1 IU D₃/g feed) and 2) deficient (DEF; 0.025 IU D₃/g feed). At age 113 d, tibialis anterior (TA), quadriceps (quads) and brain were harvested from 42 mice (22 M and 20 F), whereas the remaining 60 mice (34 M and 26 F) were followed to endpoint.

Results

During disease progression, DEF mice had 25% (P = 0.022) lower paw grip endurance AUC and 19% (P = 0.017) lower motor performance AUC vs. AI mice. Prior to disease onset (CS 2), DEF mice had 36% (P = 0.016) lower clinical score (CS) vs. AI mice. DEF mice reached CS 2 six days later vs. AI mice (P = 0.004), confirmed by a logrank test which revealed that DEF mice reached CS 2 at a 43% slower rate vs. AI mice (HR = 0.57; 95% CI: 0.38, 1.74; P = 0.002). Body weight-adjusted TA (AI: r = 0.662, P = 0.001; DEF: r = 0.622, P = 0.006) and quads (AI: r = 0.661, P = 0.001; DEF: r = 0.768; P<0.001) weights were strongly correlated with age at CS 2.

Conclusion

Vitamin D₃ deficiency improves early disease severity and delays disease onset, but reduces performance in functional outcomes following disease onset, in the high-copy G93A mouse.     

Functional significance of vitamin D receptor FokI polymorphism in human breast cancer cells

Background

The FokI vitamin D receptor (VDR) polymorphism results in different translation initiation sites on VDR. In the VDRff variant, initiation of translation occurs at the first ATG site, giving rise to a full length VDR protein of 427 amino acids. Conversely, in the VDRFF variant, translation begins at the second ATG site, resulting in a truncated protein with three less amino acids. Epidemiological studies have paradoxically implicated this polymorphism with increased breast cancer risk. 1α,25 (OH)₂D₃, the active metabolite of vitamin D, is known to inhibit cell proliferation, induce apoptosis and potentiate differentiation in human breast cancer cells. It is well documented that 1α,25 (OH)₂D₃ downregulates estrogen receptor α expression and inhibits estrogen mediated signaling in these cells. The functional significance of the VDR FokI polymorphism in vitamin D action is undefined.

Methods/Findings

To elucidate the functional role of FokI polymorphism in breast cancer, MCF-7-Vector, MCF-7-VDRff and MCF-7-VDRFF stable cell lines were established from parental MCF-7 cells as single-cell clones. In response to 1α,25 (OH)₂D₃ treatments, cell growth was inhibited by 60% in VDRFF cells compared to 28% in VDRff cells. The induction of the vitamin D target gene CYP24A1 mRNA was 1.8 fold higher in VDRFF cells than in VDRff cells. Estrogen receptor-α protein expression was downregulated by 62% in VDRFF cells compared to 25% in VDRff cells. VDR protein stability was greater in MCF-7-VDRFF cells in the presence of cycloheximide. PCR array analyses of VDRff and VDRFF cells revealed increased basal expression levels of pro-inflammatory genes Cyclooxygenase-2, Interleukin-8 and Chemokine (C-C Motif) Ligand 2 in MCF-7-VDRff cells by 14, 52.7 and 5 fold, respectively.

Conclusions/Significance

These results suggest that a VDRff genotype may play a role in amplifying aggressive breast cancer, paving the way for understanding why some breast cancer cells respond inefficiently to vitamin D treatment.     

Associations of serum 25-hydroxyvitamin D, parathyroid hormone and calcium with cardiovascular risk factors: analysis of 3 NHANES cycles (2001-2006)

Background

Increasing evidence suggests a role for mineral metabolism in cardiovascular disease risk. 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), and calcium may be directly associated with cardiovascular risk factors or mediated by each other.

Methodology/Principal Findings

We combined data for adult participants in three cycles of the National Health and Nutrition Examination Survey (2001–2, 2003–4, 2005–6), a representative sample of the civilian, non-institutionalized US population (N = 3,958). Using this data we examined joint associations of 25(OH)D, PTH and calcium with a range of cardiovascular risk factors. 25(OH)D was inversely associated with fasting insulin (mean difference in insulin per 1 standard deviation 25(OH)D: −0.053 (95%CI: −0.091, −0.015)), glucose (−0.046 95%CI: −0.081, −0.012) and systolic blood pressure (SBP) (−0.032 95%CI: −0.062, −0.001), and positively associated with high density lipoprotein cholesterol HDL-c (0.088 95%CI: 0.044, 0.148), after adjustment for ethnicity, smoking, socio-economic status and waist circumference. PTH was positively associated with diastolic blood pressure (0.110, 95%CI: 0.055, 0.164) in confounder adjusted models, but was not associated with other cardiovascular risk factors. Albumin adjusted calcium was associated with triglycerides (0.102 95%CI: 0.063, 0.141), postload glucose (0.078, 95%CI: 0.025, 0.130), fasting insulin (0.074, 95%CI: 0.044, 0.104), HbA1c (0.070, 95%CI: 0.036, 0.105), SBP (0.064, 95%CI: 0.028, 0.100), fasting glucose (0.055, 95%CI: 0.018, 0.092) and low density lipoprotein cholesterol (0.052, 95%CI: 0.014, 0.091). With mutual adjustment for each other, these associations remained essentially unchanged.

Conclusions/Significance

Lower levels of 25(OH)D and higher levels of calcium and PTH appear to be associated with different cardiovascular risk factors and may therefore affect cardiovascular disease risk through different mechanisms.     

Ethnic-specific differences in vitamin d status is associated with adiposity

Background

Low circulating 25 hydroxyvitamin D [25(OH)D] concentrations are common in obesity (BMI ≥30 kg/m²) and a negative relationship with body fat distribution has recently been reported. Ethnic-specific differences in body fat distribution have been described with South Asians are reported to have greater visceral adipose tissue (VAT), which could influence circulating 25(OH)D concentrations. The objective of this study is to investigate the relationship between plasma 25(OH)D, adiposity, and body fat distribution in Europeans and South Asians.

Methods/Principal Findings

187 Europeans and 192 South Asians were assessed for demographics, anthropometrics, and plasma 25(OH)D concentrations. Subcutaneous adipose tissue (SAT) and VAT were quantified by CT scan, and percent body fat by DEXA. Data were assessed by general linear models. South Asians had lower (P<0.001) plasma 25(OH)D concentrations and higher VAT (P = 0.04) than Europeans. Plasma 25(OH)D concentrations were negatively (P<0.05) associated with BMI, waist circumference, percent body fat, total adipose tissue, VAT, and SAT in unadjusted models and negatively (P<0.05) associated with VAT, SAT, and percent body fat after adjusting for BMI, ethnicity, age, and season of blood collection in males and females. When percent body fat, VAT, and SAT were included in the same model, only VAT remained negatively (P<0.05) associated with plasma 25(OH)D concentrations. Ethnicity remained significant in all models (P<0.001).

Conclusion

Compared to other adipose tissue compartments, VAT may have a distinct role in determining plasma 25(OH)D concentrations, which may account for the lower levels in South Asians.     

Pre-diagnostic circulating vitamin D and risk of melanoma in men

Purpose

Various studies have examined the association between serum vitamin D levels and different cancers; however, this is the first prospective study of this association with melanoma risk. The aim of this study is to investigate the association between serum vitamin D [25(OH)D] levels and melanoma in a cohort of older, middle-aged Finnish male smokers.

Methods

We conducted a nested case-control study within the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study. From the ATBC cohort, 368 subjects were chosen for our study; 92 participants that developed melanoma and 276 matched control subjects. At study baseline, lifestyle questionnaires and blood samples were collected. Serum 25(OH)D was modeled as three sets of categorical variables: clinically-defined categories, season-specific quartiles and season-adjusted residual quartiles. Conditional logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (95% CIs) to estimate the association between circulating vitamin D and melanoma risk.

Results

Overall no association of serum 25(OH)D and melanoma risk was observed. A decreased risk of developing melanoma was observed in the middle categories compared to the lowest category, albeit not significant.

Conclusion

Results indicate no association between serum 25(OH)D levels and melanoma. Additional studies, including possibly consortium efforts, are needed to investigate the association between serum 25(OH)D levels and risk of melanoma in larger, more diverse study populations.     

BCG Vaccination: A Role for Vitamin D?

Background

BCG vaccination is administered in infancy in most countries with the aim of providing protection against tuberculosis. There is increasing interest in the role of vitamin D in immunity to tuberculosis. This study objective was to determine if there was an association between circulating 25(OH)D concentrations and BCG vaccination status and cytokine responses following BCG vaccination in infants.

Methods

Blood samples were collected from UK infants who were vaccinated with BCG at 3 (n = 47) and 12 (n = 37) months post BCG vaccination. These two time-points are denoted as time-point 1 and time-point 2. Two blood samples were also collected from age-matched unvaccinated infants (n = 32 and 28 respectively), as a control group. Plasma vitamin D concentrations (25(OH)D) were measured by radio-immunoassay. The cytokine IFNγ was measured in supernatants from diluted whole blood stimulated with M.tuberculosis (M.tb) PPD for 6 days.

Results

58% of infants had some level of hypovitaminosis (25(OH)D <30ng/ml) at time-point 1, and this increased to 97% 9 months later. BCG vaccinated infants were almost 6 times (CI: 1.8–18.6) more likely to have sufficient vitamin D concentrations than unvaccinated infants at time-point 1, and the association remained strong after controlling for season of blood collection, ethnic group and sex. Among vaccinees, there was also a strong inverse association between IFNγ response to M.tb PPD and vitamin D concentration, with infants with higher vitamin D concentrations having lower IFNγ responses.

Conclusions

Vitamin D may play an immuno-regulatory role following BCG vaccination. The increased vitamin D concentrations in BCG vaccinated infants could have important implications: vitamin D may play a role in immunity induced by BCG vaccination and may contribute to non-specific effects observed following BCG vaccination.     

Vitamin d, parathyroid hormone and their associations with hypertension in a chinese population

Background

Conflicting reports support or refute an association between vitamin D deficiency with high levels of parathyroid hormone (PTH) and raised blood pressure or hypertension.

Objective

To explore the associations of serum vitamin D and PTH levels with blood pressure and risk of hypertension in a Chinese population.

Methods

A population-based cross-sectional study was conducted among 1,420 Chinese participants, aged 20–83 years, in 2010. Anthropometric phenotypes and blood pressure were evaluated. Serum lipids, 25-hydroxyvitamin D [25(OH)D] and PTH were measured.

Results

One thousand four hundred and twenty participants, including 566 women (39.9%), were evaluated in 2010. Four hundred and eighty seven were hypertensive (34.3%), of whom 214 (43.9%) received antihypertensive treatment. The median concentrations of serum 25(OH)D and PTH were 22.0 ng/ml and 2.83 pmol/l, respectively. Serum 25(OH)D and natural log of PTH levels were not independently associated with blood pressure in a multivariable adjusted linear regression analysis of 1,206 participants not receiving antihypertensive treatment (P>0.05). In logistic regression analyses, serum 25(OH)D levels were not associated with risk of hypertension in single and multiple regression models. One unit increments of natural log of PTH levels were significantly associated with risk of hypertension in the crude model (OR = 1.78, 95% confidence interval 1.38–2.28, P<0.0001) and model adjusted for age and sex (OR = 1.41, 95% confidence interval 1.08–1.83, P = 0.01). However, these associations were attenuated and became nonsignificant (OR = 1.29, 95% confidence interval 0.98–1.70, P = 0.07) after further adjustment for body mass index, current alcohol intake, current smoking, glomerular filtration rate and family history of hypertension.

Conclusions

Serum vitamin D and PTH levels are not independently associated with blood pressure or risk of hypertension in a Chinese population.     

Oral Supplementation with Cholecalciferol 800 IU Ameliorates Albuminuria in Chinese Type 2 Diabetic Patients with Nephropathy

Background

Low vitamin D levels can be associated with albuminuria, and vitamin D analogs are effective anti-proteinuric agents. The aim of this study was to investigate differences in vitamin D levels between those with micro- and those with macroalbuminuria, and to determine whether low dose cholecalciferol increases vitamin D levels and ameliorates albuminuria.

Methods

Two studies were performed in which 25-OH vitamin D₃ (25(OH)D₃) concentrations were determined by electrochemiluminescence immunoassay: 1) a cross-sectional study of patients with type 2 diabetes mellitus (T2DM) (n = 481) and healthy controls (n = 78); and 2) a longitudinal study of T2DM patients with albuminuria treated with conventional doses, 800 IU, of cholecalciferol for 6 months (n = 22), and a control group (n = 24).

Results

1) Cross-sectional study: Compared to controls and T2DM patients with normoalbuminuria, serum 25(OH)D₃ concentrations were significantly lower in patients with macro-albuminuria, but not in those with micro-albuminuria. Serum 25(OH)D₃ levels were independently correlated with microalbuminuria. 2) Longitudinal study: Cholecalciferol significantly decreased microalbuminuria in the early stages of treatment, in conjunction with an increase in serum 25(OH)D₃ levels.

Conclusions

Low vitamin D levels are common in type 2 diabetic patients with albuminuria, particularly in patients with macroalbuminuria, but not in those with microalbuminuria. Conventional doses of cholecalciferol may have antiproteinuric effects on Chinese type 2 diabetic patients with nephropathy.     

Pre-diagnostic plasma 25-hydroxyvitamin D levels and risk of non-melanoma skin cancer in women

Background

Recent reports have shown that vitamin D status was inversely associated with the risk of various cancers. However, few studies examined the association between vitamin D levels and risk of skin cancer.

Methods

We prospectively evaluated the association between baseline plasma 25(OH)D levels and the risk of incident squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) among 4,641 women from the Nurses’ Health Study (NHS) and the NHS II with 510 incident BCC cases and 75 incident SCC cases. We used multivariate logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Plasma 25(OH)D levels were positively associated with risk of BCC after adjusting for age at blood draw, season of blood draw, lab batch, hair color, burning tendency, the number of sunburns, and ultra-violet B flux of residence at blood collection. Women in the highest quartile of 25(OH)D had more than 2-fold increased risk of BCC compared with women in the lowest quartile (OR = 2.07, 95% CI = 1.52–2.80, P for trend <0.0001). We also found a significantly positive association between plasma 25(OH)D levels and SCC risk after adjusting for the same covariates (OR, highest vs. lowest quartile  = 3.77, 95% CI = 1.70–8.36, P for trend  = 0.0002).

Conclusion

In this prospective study of women, plasma vitamin D levels were positively associated with non-melanoma skin cancer risk. Considering that most circulating vitamin D is due to sun exposure, the positive association between plasma vitamin D and non-melanoma skin cancer is confounded by sun exposure. Our data suggest that one-time measurement of plasma vitamin D levels may reasonably reflect long-term sun exposure and predict the risk of non-melanoma skin cancer.     

Low vitamin D in narcolepsy with cataplexy

Background

Narcolepsy with cataplexy (NC) is currently thought to be an autoimmune-mediated disorder in which environmental risk factors make a significant contribution to its development. It was proposed that vitamin D deficiency plays a role in autoimmune diseases. Here we investigated whether NC can be associated with 25-hydroxyvitamin D (25(OH)D) level deficiency in patients with NC compared with gender- and age-matched normal controls.

Methodology

Serum level of 25 (OH)D was determined in 51 European patients with typical NC compared to 55 age-, gender-, and ethnicity-matched healthy controls. Demographic and clinical data (age at onset, duration and severity of disease at baseline, and treatment intake at time of study) and season of blood sampling were collected to control for confounding variables.

Principal Findings

Serum 25(OH)D concentration was lower in NC compared to controls (median, 59.45 nmol/l [extreme values 24.05–124.03] vs. 74.73 nmol/l [26.88–167.48] p = 0.0039). Patients with NC had significantly greater vitamin D deficiency (<75 nmol/l) than controls (72.5% vs 50.9%, p = 0.0238). Division into quartiles of the whole sample revealed that the risk of being affected with NC increased with lower 25(OH)D level, with a 5.34 OR [1.65–17.27] for the lowest quartile (p = 0.0051). Further adjustment for BMI did not modify the strength of the association (OR: 3.63, 95% CI = 1.06–12.46, p = 0.0191). No between BMI and 25(OH)D interaction, and no correlation between 25(OH)D level and disease duration or severity or treatment intake were found in NC.

Conclusion

We found a higher frequency of vitamin D deficiency in NC. Further studies are needed to assess the contribution of hypovitaminosis D to the risk of developing narcolepsy, and to focus on the utility of assessing vitamin D status to correct potential deficiency.     

1,25-Dihydroxyvitamin D3 inhibits the differentiation and migration of T(H)17 cells to protect against experimental autoimmune encephalomyelitis

Background

Vitamin D₃, the most physiologically relevant form of vitamin D, is an essential organic compound that has been shown to have a crucial effect on the immune responses. Vitamin D₃ ameliorates the onset of the experimental autoimmune encephalomyelitis (EAE); however, the direct effect of vitamin D₃ on T cells is largely unknown.

Methodology/Principal Findings

In an in vitro system using cells from mice, the active form of vitamin D₃ (1,25-dihydroxyvitamin D₃) suppresses both interleukin (IL)-17-producing T cells (T_H17) and regulatory T cells (Treg) differentiation via a vitamin D receptor signal. The ability of 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) to reduce the amount of IL-2 regulates the generation of Treg cells, but not T_H17 cells. Under T_H17-polarizing conditions, 1,25(OH)₂D₃ helps to increase the numbers of IL-10-producing T cells, but 1,25(OH)₂D₃''s negative regulation of T_H17 development is still defined in the IL-10^−/− T cells. Although the STAT1 signal reciprocally affects the secretion of IL-10 and IL-17, 1,25(OH)₂D₃ inhibits IL-17 production in STAT1^−/− T cells. Most interestingly, 1,25(OH)₂D₃ negatively regulates CCR6 expression which might be essential for T_H17 cells to enter the central nervous system and initiate EAE.

Conclusions/Significance

Our present results in an experimental murine model suggest that 1,25(OH)₂D₃ can directly regulate T cell differentiation and could be applied in preventive and therapeutic strategies for T_H17-mediated autoimmune diseases.     

Antiviral therapy and outcomes of patients with pneumonia caused by influenza A pandemic (H1N1) virus

Background

There is limited data on the clinical outcome of patients with pandemic H1N1 (pH1N1) pneumonia who received oseltamivir treatment, especially when the treatment was administered more than 48 hours after symptom onset.

Methods

During the pandemic in 2009, a cohort of pH1N1 influenza pneumonia was built in China, and their clinical information was collected systematically, and analyzed with Cox models.

Results

920 adults and 541 children with pneumonia who didn''t receive corticosteroids were analyzed. In-hospital mortality was higher in adults who did not receive antiviral therapy (18.2%) than those with who received oseltamivir ≤ 2days (2.9%), between 2–5 days (4.6%) and >5 days after illness onset (4.9%), p<0.01. A similar trend was observed in pediatric patients. Cox regression showed that at 60 days after symptoms onset, 11 patients (10.8%) who did not receive antivirals died versus 4 (1.8%), 18 (3.3%), and 23 (3.7%) patients whose oseltamivir treatment was started ≤ 2days, between 2–5days, and >5 days, respectively. For males patients, aged ≥ 14 years and baseline PaO₂/FiO₂<200, oseltamivir administration reduced the mortality risk by 92.1%, 88% and 83.5%, respectively. Higher doses of oseltamivir (>3.8 mg/kg/d) did not improve clinical outcome (mortality, higher dose 2.5% vs standard dose 2.8%, p>0.05).

Conclusions

Antiviral therapy might reduce mortality of patients with pH1N1 pneumonia, even when initiated more than 48 hours after onset of illness. Greater protective effects might be in males, patients aged 14–60 years, and patients with PaO₂/FiO₂<200.