Vitamin D Deficiency and Leisure Time Activities in the Elderly: Are All Pastimes the Same?

Background

Optimal vitamin D status is important for overall health and well-being, particularly in the elderly. Although vitamin D synthesis in the skin declines with age, exposure to sunlight still seems to help older-aged adults to achieve adequate serum 25-hydroxyvitamin D (25OHD) levels. Elderly people would therefore benefit from outdoor leisure activities, but the effects of different types of pastime on serum 25OHD levels have yet to be thoroughly investigated.

Aims

To assess the association of different pastimes with 25OHD deficiency in elderly subjects.

Methods

A sample of 2,349 community-dwelling elderly individuals (1,389 females and 960 males) enrolled in the Progetto Veneto Anziani was analyzed. Brisk walking, cycling, gardening and fishing were classed as outdoor activities, and dancing and gym workouts as indoor pastimes. Any activities undertaken for at least 1 hour/week during the previous month were considered as being practiced regularly. Logistic regression models were used to estimate the association between different pastimes and 25OHD deficiency.

Results

Serum 25OHD levels were significantly higher in individuals who engaged in outdoor pastimes (+25% in women, +27.7% in men) compared to those who did not. In particular, subjects regularly practicing gardening or cycling had higher serum 25OHD levels than those who did not, whereas 25OHD levels differed little between subjects who did or did not undertake indoor activities. Among the outdoor pastimes considered, logistic regression analysis confirmed a lower likelihood of vitamin D deficiency (25OHD<50 nmol/L) for cyclists (OR 0.51, 95% CI 0.37–0.69 in women; OR 0.50, 95% CI 0.29–0.87 in men) and gardeners (OR 0.62, 95% CI 0.47–0.83 in women; OR 0.46, 95% CI 0.26–0.80), but not for brisk walkers.

Conclusions

Regular cycling and gardening reduce the likelihood of inadequate vitamin D status in Caucasian elderly people, irrespective of their age, BMI and comorbidities, and of the season of the year.     

Interactions between Serum Vitamin D Levels and Vitamin D Receptor Gene FokI Polymorphisms for Renal Function in Patients with Type 2 Diabetes

Background

We aimed to examine associations among serum 25-hydroxyvitamin D (25OHD) levels, 1,25-dihyroxyvitamin D (1,25OHD) levels, vitamin D receptor (VDR) polymorphisms, and renal function based on estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.

Methods

In a cross-sectional study of 410 patients, chronic kidney disease (CKD) stage assessed by eGFR was compared with 25OHD, 1,25OHD, and VDR FokI (rs10735810) polymorphisms by an ordered logistic regression model adjusted for the following confounders: disease duration, calendar month, use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers or statins, and serum calcium, phosphate, and intact parathyroid hormone levels.

Results

1,25OHD levels, rather than 25OHD levels, showed seasonal oscillations; peak levels were seen from May to October and the lowest levels were seen from December to February. These findings were evident in patients with CKD stage 3∼5 but not stage 1∼2. eGFR was in direct proportion to both 25OHD and 1,25OHD levels (P<0.0001), but it had stronger linearity with 1,25OHD (r = 0.73) than 25OHD (r = 0.22) levels. Using multivariate analysis, 1,25OHD levels (P<0.001), but not 25OHD levels, were negatively associated with CKD stage. Although FokI polymorphisms by themselves showed no significant associations with CKD stage, a significant interaction between 1,25OHD and FokITT was observed (P = 0.008). The positive association between 1,25OHD and eGFR was steeper in FokICT and CC polymorphisms (r = 0.74) than FokITT polymorphisms (r = 0.65).

Conclusions

These results suggest that higher 1,25OHD levels may be associated with better CKD stages in patients with type 2 diabetes and that this association was modified by FokI polymorphisms.     

Pretreatment serum concentrations of 25-hydroxyvitamin D and breast cancer prognostic characteristics: a case-control and a case-series study

Background

Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity.

Methods and Findings

In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08–0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22–0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses.

Conclusion

In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women.     

Association of Serum 25-Hydroxyvitamin D with Lifestyle Factors and Metabolic and Cardiovascular Disease Markers: Population-Based Cross-Sectional Study (FIN-D2D)

Objectives

Low serum 25-hydroxyvitamin D (25OHD) level has been associated with an increased risk of several chronic diseases. Our aim was to determine lifestyle and clinical factors that are associated with 25OHD level and to investigate connection of 25OHD level with metabolic and cardiovascular disease markers.

Design

In total, 2868 Finnish men and women aged 45–74 years participated in FIN-D2D population-based health survey in 2007. Participants that had a serum sample available (98.4%; n = 2822) were included in this study. 25OHD was measured with chemiluminescent microparticle immunoassay method.

Results

The mean 25OHD level was 58.2 nmol/l in men (n = 1348) and 57.1 nmol/l in women (n = 1474). Mean 25OHD level was lower in the younger age groups than in the older ones (p<0.0001 both in men and women). This study confirmed that low physical activity (p<0.0001 both in men and women), smoking (p = 0.0002 in men and p = 0.03 in women) and high BMI (p<0.0001 in women) are factors that independently associate with low 25OHD level. Of the metabolic and cardiovascular disease markers high triglyceride concentration (p = 0.02 in men and p = 0.001 in women) and high apolipoprotein B/apolipoprotein A1 ratio (p = 0.04 in men and p = 0.03 in women) were independently associated with low 25OHD level.

Conclusions

Higher age did not predict lower 25OHD level in this study population of aged 45–74 years which may derive from a healthy life-style of “active pensioners”. Low physical activity and smoking came up as independent lifestyle factors associated with low 25OHD level. Defining the molecular mechanisms behind the associations of 25OHD with low physical activity and smoking are important objective in future studies. The association of 25OHD with BMI, high triglyceride concentration and apolipoprotein B/apolipoprotein A1 ratio may be related to the role of vitamin D in inflammation, but more detailed studies are needed.     

Agreement of blood spot card measurements of vitamin D levels with serum, whole blood specimen types and a dietary recall instrument

Background

The ability to measure 25-hydroxyvitamin D (25OHD) levels from blood spot cards can simplify sample collection versus samples obtained by venipuncture, particularly in populations in whom it is difficult to draw blood. We sought to validate the use of blood spot samples for the measurement of 25OHD compared to serum or whole blood samples and correlate the measured levels with intake estimated from dietary recall.

Methods

Utilizing 109 biological mothers of infants enrolled in the Tennessee Children''s Respiratory Initiative cohort, we measured 25OHD levels through highly selective liquid chromatography–tandem mass spectrometry on samples from blood spot cards, serum, and whole blood collected at enrollment. Dietary questionnaires (n = 65) were used to assess 25OHD intake by dietary recall. Sample collection measures were assessed for agreement and 25OHD levels for association with dietary 25OHD intake.

Results

The mean absolute differences (95%CI) in 25OHD levels measured between whole blood and blood spot (n = 50 pairs) or serum and blood spot (n = 20) were 3.2 (95%CI:1.6, 4.8) ng/ml and 1.5 (95%CI:−0.5,3.4) ng/mL. Intake by dietary recall was marginally associated with 25OHD levels after adjustment for current smoking and race in linear regression.

Discussion

25OHD levels determined by mass spectrometry from blood spot cards, serum and whole blood show relatively good agreement, although 25OHD levels are slightly lower when measured by blood spot cards. Blood spot samples are a less invasive means of obtaining 25OHD measurements, particularly in large population-based samples, or among children when venipuncture may decrease study participation.     

Vitamin D and physical performance in elderly subjects: the Pro.V.A study

Background

The role of Vitamin D in musculoskeletal functionality among elderly people is still controversial. We investigated the association between serum 25-hydroxyvitamin D (25OHD) levels and physical performance in older adults.

Methods

2694 community-dwelling elderly women and men from the Progetto Veneto Anziani (Pro.V.A.) were included. Physical performances were assessed by: tandem test, 5 timed chair stands (TCS), gait speed, 6-minute walking (6 mW) distance, handgrip strength, and quadriceps strength. For each test, separate general linear models and loess plots were obtained in both genders, in relation to serum 25OHD concentrations, controlling for several potential confounders.

Results

Linear associations with 25OHD levels were observed for TCS, gait speed, 6 mW test and handgrip strength, but not for tandem test and quadriceps strength. After adjusting for potential confounders, linear associations with 25OHD levels were still evident for the 6 mW distance in both genders (p = .0002 in women; <.0001 in men), for TCS in women (p = .004) and for gait speed (p = .0006) and handgrip strength (p = .03) in men. In loess analyses, performance in TCS in women, in gait speed and handgrip strength in men and in 6 mW in both genders, improved with increasing levels of 25OHD, with most of the improvements occurring for 25OHD levels from 20 to 100 nmol/L.

Conclusion

lower 25OHD levels are associated with a worse coordination and weaker strength (TCS) in women, a slower walking time and a lower upper limb strength in men, and a weaker aerobic capacity (6 mW) in both genders. For optimal physical performances, 25OHD concentrations of 100 nmol/L appear to be more advantageous in elderly men and women, and Vitamin D supplementation should be encouraged to maintain their 25OHD levels as high as this threshold.     

Seasonal Genetic Influence on Serum 25-Hydroxyvitamin D Levels: A Twin Study

Background

Although environmental factors, mainly nutrition and UV-B radiation, have been considered major determinants of vitamin D status, they have only explained a modest proportion of the variation in serum 25-hydroxyvitamin D. We aimed to study the seasonal impact of genetic factors on serum 25-hydroxyvitamin D concentrations.

Methodology/Principal findings

204 same-sex twins, aged 39–85 years and living at northern latitude 60°, were recruited from the Swedish Twin Registry. Serum 25-hydroxyvitamin D was analysed by high-pressure liquid chromatography and mass spectrometry. Genetic modelling techniques estimated the relative contributions of genetic, shared and individual-specific environmental factors to the variation in serum vitamin D. The average serum 25-hydroxyvitamin D concentration was 84.8 nmol/l (95% CI 81.0–88.6) but the seasonal variation was substantial, with 24.2 nmol/l (95% CI 16.3–32.2) lower values during the winter as compared to the summer season. Half of the variability in 25-hydroxyvitamin D during the summer season was attributed to genetic factors. In contrast, the winter season variation was largely attributable to shared environmental influences (72%; 95% CI 48–86%), i.e., solar altitude. Individual-specific environmental influences were found to explain one fourth of the variation in serum 25-hydroxyvitamin D independent of season.

Conclusions/Significance

There exists a moderate genetic impact on serum vitamin D status during the summer season, probably through the skin synthesis of vitamin D. Further studies are warranted to identify the genes impacting on vitamin D status.     

Independent Association of Circulating Vitamin D Metabolites with Anemia Risk in Patients Scheduled for Cardiac Surgery

Background

Preoperative anemia is considered an independent risk factor of poor clinical outcome in cardiac surgical patients. Low vitamin D status may increase anemia risk.

Methods

We investigated 3,615 consecutive patients scheduled for cardiac surgery to determine the association between preoperative anemia (hemoglobin [Hb] <12.5 g/dL) and circulating levels of the vitamin D metabolites 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25[OH]₂D).

Results

Of the study cohort, 27.8 % met the criteria for anemia. In patients with deficient 25OHD levels (<30 nmol/l) mean Hb concentrations were 0.5 g/dL lower than in patients with adequate 25OHD levels (50.0–125 nmol/l; P<0.001). Regarding 1,25(OH)₂D, mean Hb concentrations were 1.2 g/dL lower in the lowest 1,25(OH)₂D category (<40 pmol/l) than in the highest 1,25(OH)₂D category (>70 pmol/l; P<0.001). In multivariable–adjusted logistic regression analyses, the odds ratios for anemia of the lowest categories of 25OHD and 1,25(OH)₂D were 1.48 (95%CI:1.19-1.83) and 2.35 (95%CI:1.86-2.97), compared with patients who had adequate 25OHD levels and 1,25(OH)₂D values in the highest category, respectively. Anemia risk was greatest in patients with dual deficiency of 25OHD and 1,25(OH)₂D (multivariable-adjusted OR = 3.60 (95%CI:2.40-5.40). Prevalence of deficient 25OHD levels was highest in anemia of nutrient deficiency, whereas low 1,25(OH)₂D levels were most frequent in anemia of chronic kidney disease.

Conclusion

This cross-sectional study demonstrates an independent inverse association between vitamin D status and anemia risk. If confirmed in clinical trials, preoperative administration of vitamin D or activated vitamin D (in case of chronic kidney disease) would be a promising strategy to prevent anemia in patients scheduled for cardiac surgery.     

Vitamin D and Caudal Primary Motor Cortex: A Magnetic Resonance Spectroscopy Study

Background

Vitamin D is involved in brain physiology and lower-extremity function. We investigated spectroscopy in a cohort of older adults to explore the hypothesis that lower vitamin D status was associated with impaired neuronal function in caudal primary motor cortex (cPMC) measured by proton magnetic resonance spectroscopic imaging.

Methods

Twenty Caucasian community-dwellers (mean±standard deviation, 74.6±6.2 years; 35.0% female) from the ‘Gait and Brain Study’ were included in this analysis. Ratio of N-acetyl-aspartate to creatine (NAA/Cr), a marker of neuronal function, was calculated in cPMC. Participants were categorized according to mean NAA/Cr. Lower vitamin D status was defined as serum 25-hydroxyvitamin D (25OHD) concentration <75 nmol/L. Age, gender, number of comorbidities, vascular risk, cognition, gait performance, vitamin D supplements, undernourishment, cPMC thickness, white matter hyperintensities grade, serum parathyroid hormone concentration, and season of evaluation were used as potential confounders.

Results

Compared to participants with high NAA/Cr (n = 11), those with low NAA/Cr (i.e., reduced neuronal function) had lower serum 25OHD concentration (P = 0.044) and more frequently lower vitamin D status (P = 0.038). Lower vitamin D status was cross-sectionally associated with a decrease in NAA/Cr after adjustment for clinical characteristics (β = −0.41, P = 0.047), neuroimaging measures (β = −0.47, P = 0.032) and serum measures (β = −0.45, P = 0.046).

Conclusions

Lower vitamin D status was associated with reduced neuronal function in cPMC. These novel findings need to be replicated in larger and preferably longitudinal cohorts. They contribute to explain the pathophysiology of gait disorders in older adults with lower vitamin D status, and provide a scientific base for vitamin D replacement trials.     

Bone Mineral Density Measurements,Bone Markers and Serum Vitamin D Concentrations in Men with Chronic Non-Cirrhotic Untreated Hepatitis C

Introduction

The high prevalence of chronic hepatitis C (CHC) and its consequent cirrhosis has been associated with bone fragility. Whether CHC may cause bone and mineral abnormalities in the absence of hepatocellular dysfunction is still unknown. In this study we aimed to determine the prevalence of osteoporotic vertebral fractures and low BMD measurements in men with non-cirrhotic CHC. Risk factors for low BMD and fractures were also investigated.

Methods

Morphometric vertebral fractures and BMD measurements were performed in 60 non-cirrhotic untreated men with CHC and 59 healthy controls, matched for age and gender, weight and current smoking. Serum CTx, calcium, phosphate, intact PTH, alkaline phosphatase and vitamin D (25OHD) concentrations were measured in all participants. Clinical risk factors for low BMD and fractures were evaluated by a structured questionnaire as well as details regarding HCV infection.

Results

Trochanter and total femur BMD were significantly lower in CHC patients as compared to healthy men (p = 0.04). In men 50 years and older, the prevalence of osteoporosis was significantly higher among CHC patients (p = 0.01). Lower levels of physical activities and more often report of prolonged immobilization were observed among CHC patients (p<0.05). Liver inflammation and fibrosis, viral load and genotype did not correlate with BMD measurements. Bone markers and 25OHD concentrations were similar in both groups. Only a few vertebral fractures were observed.

Conclusions

Our results demonstrate that non-cirrhotic untreated CHC patients have lower BMD at the femur as compared to healthy men in spite of the absence of significant bone and mineral abnormalities.     

Determinants of Vitamin D Status in Fair-Skinned Women of Childbearing Age at Northern Latitudes

Background and Objective

Poor vitamin D status during pregnancy has been associated with unfavorable outcomes for mother and child. Thus, adequate vitamin D status in women of childbearing age may be important. The aim of this study is to investigate the determinants of 25-hydroxyvitamin D (25(OH)D) serum concentrations in women of childbearing age living in Sweden, at latitude 57–58° north.

Method

Eighty four non-pregnant, non-lactating, healthy, fair-skinned women aged between 25–40 years were included. All subjects provided blood samples, four day food records and answered questionnaires about sun exposure and lifestyle. Total serum 25(OH)D was analyzed using Roche Cobas® electrochemoluminiescent immunoassay.

Results

Mean 25(OH)D was 65.8±19.9 nmol/l and 23% of the subjects had concentrations <50 nmol/l. Only 1% had concentrations <25 nmol/l. Determinants of 25(OH)D concentrations were recent sunbed use, recent travel to southern latitude, season, estrogen contraceptive use and use of supplementary vitamin D (R² = 0.27).

Conclusion

Every fifth woman had 25(OH)D concentrations <50 nmol/l. About 30% of the variation in vitamin D status was explained by sun exposure, use of vitamin D supplements and use of estrogen contraceptives. Cutaneous vitamin D synthesis seems to be a major contributor to vitamin D status, even at northern latitudes. Thus, recommendations on safe UV-B exposure could be beneficial for vitamin D status.     

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.     

Effect of Vitamin D Supplementation on Cardiometabolic Risks and Health-Related Quality of Life among Urban Premenopausal Women in a Tropical Country – A Randomized Controlled Trial

Background

Many observational studies linked vitamin D to cardiometabolic risks besides its pivotal role in musculoskeletal diseases, but evidence from trials is lacking and inconsistent.

Aim

To determine whether Vitamin D supplementation in urban premenopausal women with vitamin D deficiency can improve cardiometabolic risks and health-related quality of life (HRQOL).

Design

A double-blind randomized controlled trial was conducted in Kuala Lumpur, Malaysia. A total of 192 vitamin D deficient (<50 nmol/l) premenopausal women were randomized to receive either vitamin D 50,000 IU or placebo once a week for 2 months and then monthly for 10 months. Primary outcomes were serum 25(OH)D, serum lipid profiles, blood pressure and HOMA-IR measured at baseline, 6 months and 12 months. HRQOL was assessed with SF-36 at baseline and 12 months.

Results

Ninety three and ninety-nine women were randomised into intervention and placebo groups respectively. After 12 months, there were significant differences in the serum 25(OH)D concentration (mean difference: 49.54; 95% CI: 43.94 to 55.14) nmol/l) and PTH levels (mean difference: −1.02; 95% CI: −1.67 to −0.38 pmol/l) in the intervention group compared to placebo group. There was significant difference between treatment group in both serum 25(OH)D and PTH. There was no effect of supplementation on HOMA-IR, serum lipid profiles and blood pressure (all p>0.05) between two groups. There was a small but significant improvement in HRQOL in the components of vitality (mean difference: 5.041; 95% CI: 0.709 to 9.374) and mental component score (mean difference: 2.951; 95% CI: 0.573 to 5.329) in the intervention group compared to placebo group.

Conclusion

Large and less frequent dosage vitamin D supplementation was safe and effective in the achievement of vitamin D sufficiency. However, there was no improvement in measured cardiometabolic risk factors in premenopausal women. Conversely vitamin D supplementation improves some components of HRQOL.

Trial Registration

Australian New Zealand Clinical Trial Registry ACTRN12612000452897     

Standardization of Misleading Immunoassay Based 25-Hydroxyvitamin D Levels with Liquid Chromatography Tandem-Mass Spectrometry in a Large Cohort Study

Background

The interest in vitamin D measurement has strongly increased in recent years. The best indicator for circulating vitamin D levels is 25-hydroxy-vitamin D (25(OH)D) which is often measured by different immunoassays. We demonstrate problems in comparability of measures by different immunoassays and the need for standardization in the context of a large population-based cohort study.

Methods

25(OH)D was measured with the immunoassays Diasorin Liaison in 2006 in 5,386 women and in the context of another project with IDS-iSYS in 4,199 men in 2009–2010 (when the Diasorin Liaison was no longer available in the version utilized in 2006). Standardization was performed by re-measuring of 25(OH)D levels in 97 men and 97 women with liquid chromatography tandem-mass spectrometry (LC-MS/MS) to obtain linear regression conversion equations.

Results

Applying a 30 nmol/L cut-off value for vitamin D deficiency would have resulted in 48.3% of women and 12.1% of men with vitamin D deficiency ahead of standardization. The large gender difference was strongly attenuated after standardization of the assays with only 15.7% of women and 14.3% of men with vitamin D deficiency. Standardization on average increased the 25(OH)D levels by 10.3 nmol/L in women and decreased 25(OH)D levels by 2.9 nmol/L in men.

Conclusion

The standardization with LC-MS/MS revealed that much of the observed gender difference was only assay-driven and the extremely high proportion of 48.3% vitamin D deficient women proved to be an exaggeration of the old version of the Diasorin-Liaison immunoassay. Standardization of 25(OH)D immunoassay results by LC-MS/MS is recommended to improve their accuracy and comparability, provided the LC-MS/MS method itself is adequately validated and standardized.     

Non-Linear Relationship between Serum 25-Hydroxyvitamin D and Hemoglobin in Korean Females: The Korean National Health and Nutrition Examination Survey 2010–2011

Background

Anemia and vitamin D deficiency are both important health issues; however, the nature of the association between vitamin D and either hemoglobin or anemia remains unresolved in the general population.

Methods

Data on 11,206 adults were obtained from the fifth Korean National Health and Nutritional Examination Survey. A generalized additive model was used to examine the threshold level for relationship between serum 25-hydroxyvitamin D [25(OH)D] and hemoglobin levels. A multivariate logistic regression for anemia was conducted according to 25(OH)D quintiles. All analyses were stratified according to sex and menstrual status.

Results

The generalized additive model confirmed a threshold 25(OH)D level of 26.4 ng/mL (male, 27.4 ng/mL; premenopausal females, 11.8 ng/mL; postmenopausal females, 13.4 ng/mL). The threshold level affected the pattern of association between 25(OH)D and anemia risk: the odds ratio of the 1^st quintile but not the 2^nd, 3^rd, and 4^th quintiles were significantly different from the 5^th quintile in both premenopausal and postmenopausal females, however there was no obvious trend in males.

Conclusions

This population-based study demonstrated a non-linear relationship with a threshold effect between serum 25(OH)D and hemoglobin levels in females. Further interventional studies are warranted to determine whether the appropriate level of hemoglobin can be achieved by the correction of vitamin D deficiency.     

Asthma prevalence associated with geographical latitude and regional insolation in the United States of America and Australia

Background

It has been proposed that vitamin D deficiency may be responsible for an increase in the prevalence of allergic diseases and asthma worldwide. Human ability to generate physiologically required quantities of vitamin D through sun exposure is decreasing with increasing geographical latitude.

Objectives

Considering that vitamin D deficiency is usually due to lack of outdoor sun exposure, this study is designed to test the hypothesis that a higher prevalence of asthma should be expected at high relative to low geographical latitudes.

Methods

Linear regression analyses are performed on asthma prevalence in the U.S. adult population vs. geographical latitude, insolation, air temperature, and air pollution (PM_2.5) for 97 major metropolitan/micropolitan statistical areas of the continental United States of America and on general population asthma prevalence vs. geographical latitude in eight metropolitan areas of Australia.

Results

A 10° change in geographical latitude from southern to northern regions of the Eastern Seaboard is associated with a 2% increase in adult asthma prevalence (p<0.001). Total insolation in winter months is almost as strong as latitude in its ability to explain the observed spatial variation in the prevalence of asthma (r² = 0.43; p<0.001). Similar results are obtained using the Australian data (r² = 0.73; p<0.01), suggesting a consistent association between the latitude/insolation and asthma prevalence worldwide.

Conclusions

The results of this study suggest that, as a known modulator of the immune response closely linked with the geographical latitude and erythemal UV irradiation, vitamin D may play an important role in the development/exacerbation of asthma.     

A Novel Approach for Prediction of Vitamin D Status Using Support Vector Regression

Background

Epidemiological evidence suggests that vitamin D deficiency is linked to various chronic diseases. However direct measurement of serum 25-hydroxyvitamin D (25(OH)D) concentration, the accepted biomarker of vitamin D status, may not be feasible in large epidemiological studies. An alternative approach is to estimate vitamin D status using a predictive model based on parameters derived from questionnaire data. In previous studies, models developed using Multiple Linear Regression (MLR) have explained a limited proportion of the variance and predicted values have correlated only modestly with measured values. Here, a new modelling approach, nonlinear radial basis function support vector regression (RBF SVR), was used in prediction of serum 25(OH)D concentration. Predicted scores were compared with those from a MLR model.

Methods

Determinants of serum 25(OH)D in Caucasian adults (n = 494) that had been previously identified were modelled using MLR and RBF SVR to develop a 25(OH)D prediction score and then validated in an independent dataset. The correlation between actual and predicted serum 25(OH)D concentrations was analysed with a Pearson correlation coefficient.

Results

Better correlation was observed between predicted scores and measured 25(OH)D concentrations using the RBF SVR model in comparison with MLR (Pearson correlation coefficient: 0.74 for RBF SVR; 0.51 for MLR). The RBF SVR model was more accurately able to identify individuals with lower 25(OH)D levels (<75 nmol/L).

Conclusion

Using identical determinants, the RBF SVR model provided improved prediction of serum 25(OH)D concentrations and vitamin D deficiency compared with a MLR model, in this dataset.     

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.     

Change in Vitamin D Levels Occurs Early after Antiretroviral Therapy Initiation and Depends on Treatment Regimen in Resource-Limited Settings

Study Background

Vitamin D has wide-ranging effects on the immune system, and studies suggest that low serum vitamin D levels are associated with worse clinical outcomes in HIV. Recent studies have identified an interaction between antiretrovirals used to treat HIV and reduced serum vitamin D levels, but these studies have been done in North American and European populations.

Methods

Using a prospective cohort study design nested in a multinational clinical trial, we examined the effect of three combination antiretroviral (cART) regimens on serum vitamin D levels in 270 cART-naïve, HIV-infected adults in nine diverse countries, (Brazil, Haiti, Peru, Thailand, India, Malawi, South Africa, Zimbabwe and the United States). We evaluated the change between baseline serum vitamin D levels and vitamin D levels 24 and 48 weeks after cART initiation.

Results

Serum vitamin D levels decreased significantly from baseline to 24 weeks among those randomized to efavirenz/lamivudine/zidovudine (mean change: −7.94 [95% Confidence Interval (CI) −10.42, −5.54] ng/ml) and efavirenz/emtricitabine/tenofovir-DF (mean change: −6.66 [95% CI −9.40, −3.92] ng/ml) when compared to those randomized to atazanavir/emtricitabine/didanosine-EC (mean change: −2.29 [95% CI –4.83, 0.25] ng/ml). Vitamin D levels did not change significantly between week 24 and 48. Other factors that significantly affected serum vitamin D change included country (p<0.001), season (p<0.001) and baseline vitamin D level (p<0.001).

Conclusion

Efavirenz-containing cART regimens adversely affected vitamin D levels in patients from economically, geographically and racially diverse resource-limited settings. This effect was most pronounced early after cART initiation. Research is needed to define the role of Vitamin D supplementation in HIV care.     

Risk Factors for Vitamin D Deficiency among Veterans with and without HIV Infection

Objectives

We aimed to describe and compare the prevalence of vitamin D deficiency between HIV-negative and HIV-infected veterans in the southern United States, and to determine risk factors for vitamin D deficiency for HIV infected patients.

Methods

Cross-sectional, retrospective study including all patients followed at the Atlanta VA Medical Center with the first 25-hydroxyvitamin D [25(OH)D] level determined between January 2007 and August 2010. Multivariate logistic regression analysis was used to determine risk factors associated with vitamin D deficiency (< 20 ng/ml).

Results

There was higher prevalence of 25(OH)D deficiency among HIV-positive compared to HIV-negative patients (53.2 vs. 38.5%, p <0.001). Independent risk factors for vitamin D deficiency in HIV + patients included black race (OR 3.24, 95% CI 2.28–4.60), winter season (OR 1.39, 95% CI 1.05–1.84) and higher GFR (OR 1.01, CI 1.00–1.01); increasing age (OR 0.98, 95% CI 0.95–0.98), and tenofovir use (OR 0.72, 95% CI 0.54–0.96) were associated with less vitamin D deficiency.

Conclusions

Vitamin D deficiency is a prevalent problem that varies inversely with age and affects HIV-infected patients more than other veterans in care. In addition to age, tenofovir and kidney disease seem to confer a protective effect from vitamin D deficiency in HIV-positive patients.