Screening for vitamin D deficiency: defining vitamin D deficiency, target thresholds of treatment and estimating the benefits of treatment

Vitamin D sufficiency has been associated with improved health outcomes but cost benefit analyses of published data adopt a number of assumptions. Firstly, definitions of vitamin D deficiency vary. Secondly, available methods used for the analysis of 25-hydroxyvitamin D (25OHD) have significant limitations which could affect the adoption of specific target thresholds for treatment. Thirdly, although a variety of diseases are associated with vitamin D deficiency, randomised clinical trial data demonstrating the benefit of vitamin D supplementation only exist for the prevention of falls or fractures. This review will summarise the current evidence regarding an appropriate target threshold of 25OHD and review proposed therapeutic target thresholds of treatment. The limitations of current methods will be reviewed and objective data relating to the costs of diagnosis, the costs of treatment, and the level of evidence that screening could lessen disease burden in the community, will be provided. Finally, information needed by governments and health organisations to help justify population screening and what strategies could be adopted to make screening more cost-effective will be explored.     

Proteoglycan synthesis in vitamin D-deficient cartilage: recovery from vitamin D deficiency

Vitamin D appears to be required for mineralization of skeletal elements. There is also evidence that cartilage proteoglycans may be involved in the regulation of mineralization. Previous studies have shown an alteration in the structure of the proteoglycans of the epiphyseal growth cartilage as a result of the decrease in serum calcium related to deficiency of dietary vitamin D. Vitamin D deficiency also induces a thickening of the epiphyseal growth plate presumably because of the inhibition of maturation of the growth plate chondrocytes. In order to compare the effect on proteoglycan structure with that on growth plate morphology, the proteoglycans of healing epiphyseal cartilage were characterized. The results indicate that, consistent with previous data, in vitamin D-deficient hatching chicks, the proteoglycans of the growth cartilage, but not of the articular cartilage, are smaller in monomer size with slightly smaller chondroitin sulfate chains whose sulfation pattern is unaltered. Sternal cartilage proteoglycans are unaffected. During recovery from vitamin D deficiency, the proteoglycans isolated from the growth cartilage are still not completely normal one day after supplementation with vitamin D, but are indistinguishable from normal by four days. In addition, the results conflict with those of a previous study in which only growth cartilage of hatchling chicks, not sternal or articular cartilage, was reported to synthesize large proteoglycans. Instead, all of these cartilages in the normal chicken have been found in this study to produce large proteoglycans of a size typical for mammalian cartilage and embryonic chick cartilage.     

Behavioral correlates of social anxiety

High school students' scores on a paper-and-pencil test of social anxiety were correlated with talking, eye contact and gesturing behaviors during a 10-min vidotaped interview. Results showed that high anxious subjects talked less while listening to instruction. They also held the gaze for less total time and in bouts of shorter duration while they were talking;while they were listening, they were significantly more variable in their average bout duration. Within-group variability suggested that non-verbal behaviour should be analysed according to individual rather than group differences.     

The association of vitamin D deficiency with non-alcoholic fatty liver disease

OBJECTIVE:

Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease.

METHODS:

We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease.

RESULTS:

The non-alcoholic fatty liver disease group had significantly higher fasting blood glucose (p = 0.005), uric acid (p = 0.001), aspartate aminotransferase (p<0.001), alanine aminotransferase (p<0.001), γ-glutamyltransferase (p<0.0001), alkaline phosphatase (p = 0.028), HbA1c (p<0.001), ferritin (p<0.001), insulin (p = 0.016), C-peptide (p = 0.001), HOMA-IR (p = 0.003), total cholesterol (p = 0.001), triglyceride (p = 0.001) and white blood cell (p = 0.04) levels. In contrast, the non-alcoholic fatty liver disease group had significantly lower 25(OH)D levels (12.3±8.9 ng/dl, p<0.001) compared with those of the control group (20±13.6 ng/dl).

CONCLUSIONS:

In this study, we found lower serum 25(OH)D levels in patients with non-alcoholic fatty liver disease than in subjects without non-alcoholic fatty liver disease. To establish causality between vitamin D and non-alcoholic fatty liver disease, further interventional studies with a long-term follow-up are needed.     

Developmental vitamin D deficiency alters dopamine turnover in neonatal rat forebrain

There is growing evidence that low vitamin D impacts adversely on brain development. The current study investigated the impact of developmental vitamin D (DVD) deficiency on dopamine and serotonin metabolism in the neonatal rat brain. DVD-deficiency resulted in an altered dopaminergic metabolic profile in the forebrain, with a decrease in the conversion of dihydroxyphenylacetic acid (DOPAC) to homovanillic acid (HVA). Correspondingly, expression of the enzyme required for this conversion, catechol-O-methyl transferase (COMT), was decreased. These results suggest that DVD-deficiency influences dopamine turnover during development.     

The world epidemic of sleep disorders is linked to vitamin D deficiency

An observation of sleep improvement with vitamin D supplementation led to a 2 year uncontrolled trial of vitamin D supplementation in 1500 patients with neurologic complaints who also had evidence of abnormal sleep. Most patients had improvement in neurologic symptoms and sleep but only through maintaining a narrow range of 25(OH) vitamin D3 blood levels of 60-80 ng/ml. Comparisons of brain regions associated with sleep-wake regulation and vitamin D target neurons in the diencephalon and several brainstem nuclei suggest direct central effects of vitamin D on sleep. We propose the hypothesis that sleep disorders have become epidemic because of widespread vitamin D deficiency. The therapeutic effects together with the anatomic-functional correspondence warrant further investigation and consideration of vitamin D in the etiology and therapy of sleep disorders.     

Is vitamin D deficiency involved in the immune reconstitution inflammatory syndrome?

Background  

About 20–30% of persons with HIV infection, especially those living in countries with limited resources, experience an immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral treatment. The active form of vitamin D, 1,25-dihydroxyvitamin D, is a key player in the clearance of pathogens and influences the level of inflammation and macrophage activation.     

Behavioral correlates of adherence to antiretroviral therapy

The objective of this study was to analyze the relationships between adherence to treatment and sexual and drug-taking behaviors among persons with HIV, who started combination antiretroviral therapy as their first regimen. The authors analyzed data from 366 patients enrolled in a multicenter observational cohort study conducted in infectious disease hospital units in Italy. Adherence measurement was based on responses to a self-administered questionnaire regarding following HIV physician advice on taking medications and missed appointments. Questions on sexual and drug-taking behaviors were also included in the questionnaire. The median time since starting antiretroviral therapy was 11.8 months; 37.4% of patients were on a two-drug regimen and 62.6% were on a three-drug regimen. Overall, 68 patients (18.6%) could be classified as nonadherent. The proportion of patients with viral load < or = 500 copies/mL was significantly higher among adherent patients (68%) compared with nonadherent patients (40.4%; p = .001). In multivariable analysis, age (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.42-0.98, per 10-year increment) and current use of injection (OR, 3.47; 95% CI, 1.40-8.5) or noninjection drugs (OR, 4.23; 95% Cl, 1.85-9.67) were significantly associated with nonadherence. No significant association was found between adherence and sexual behaviors. The data do not support the hypothesis that among HIV-infected person on antiretroviral therapy, poor adherence is associated with high-risk sexual behaviors that may further spread the infection.     

Association of vitamin D deficiency and frailty: A systematic review and meta-analysis

There is a biologically plausible association between low vitamin D, specifically serum 25-hydroxyvitamin D [25(OH)D] level, and frailty. We conducted a systematic review and meta-analysis to describe the association between low 25(OH)D level and frailty. We searched literature in OVID (Medline), EMBASE, Web of Knowledge and Cochrane CENTRAL Library Issue in May 2016, for cohort studies evaluating association of low 25(OH)D level with the risk of frailty. Studies were reviewed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) guidelines. A total of seven studies(17,815 participants)were eligible in our study. The prevalence of frailty ranged from 3.9% to 31.9%. The pooled OR of frailty for the lowest versus the highest level of vitamin D was 1.27 (95% CI = 1.17–1.38, I² = 59%), suggesting that low level of vitamin D was significantly associated with the risk of frailty. In addition, results of subgroups analysis indicated that low level of vitamin D was significantly associated with the risk of frailty in female (pooled OR = 1.27, 95% CI = 1.15–1.40). Similar result was also found when frailty was defined by the Fried criteria or the modified Fried criteria (pooled OR = 1.25, 95% CI = 1.14–1.37), and FRAIL scale (pooled OR = 1.55, 95% CI = 1.07–2.25). Compared to the highest level of 25(OH)D, the association between frailty and the lowest level of 25(OH)D was significant in our study.