Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment

Calcidiol, the major circulating metabolite of vitamin D, supports induction of pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates circulating calcidiol concentrations, and thus has a potential role in the prevention and treatment of infection. The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported. To characterize these effects, we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were randomized to receive adjunctive high-dose vitamin D or placebo in a clinical trial, and who fulfilled criteria for per-protocol analysis. Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia, monocytosis, hypercytokinaemia, and hyperchemokinaemia. Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses, but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4, CC chemokine ligand 5, and IFN-α. We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment. Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality.     

Vitamin D receptor genetic polymorphisms in severe and recurrent tuberculosis in children

AimTo analyze the genetic polymorphisms of vitamin D receptor FokI, TaqI, ApaI and BsmI gene polymorphisms in children with severe and recurrent tuberculosis (TB).MethodsA prospective, observational study was conducted in 35 children with severe and recurrent TB referred to our Pediatric TB clinic at a tertiary referral center for children. The blood samples were analysed for genetic polymorphisms of Vitamin D receptor with respect to FokI, TaqI, ApaI and BsmI genotypes and their individual alleles and association of various clinical and laboratory parameters were analysed.ResultTen (28.6%) children had recurrent TB and 26 (74.3%) had severe TB. The severity of TB was not associated with Ff and ff polymorphism of FokI (Odd's ratio 7.88) as compared to no FokI polymorphism. Absence of FokI polymorphism was associated with recurrent lymph node TB (Odds ratio 3.429). Presence of Tt polymorphism of TaqI (p = 0.04) and Fok1 Polymorphism [Odds ratio 7.88] were not associated with recurrent TB.ConclusionRecurrent TB was absent in presence of Tt polymorphism of TaqI. Severe TB was not associated polymorphism of Vitamin D receptor polymorphisms.     

Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from sub-Saharan Africa.

Among African immigrants in Melbourne, Victoria, Australia, we demonstrated lower geometric mean vitamin D levels in immigrants with latent tuberculosis infection than in those with no Mycobacterium tuberculosis infection (P=.007); such levels were also lower in immigrants with tuberculosis or past tuberculosis than in those with latent tuberculosis infection (P=.001). Higher vitamin D levels were associated with lower probability of any M. tuberculosis infection (P=.001) and lower probability of tuberculosis or past tuberculosis (compared with latent tuberculosis infection; P=.001).     

Vitamin D receptor gene polymorphisms and susceptibility M. tuberculosis in native Paraguayans

Tuberculosis (TB) is a significant health problem for most of the world's populations, and prevalence among indigenous groups is typically higher than among their nonindigenous neighbors. Native South Americans experience high rates of TB, but while research in several other world populations indicates that susceptibility is multifactorial, polygenic, and population-specific, little work has been undertaken to investigate factors involved in Native American susceptibility. We conducted a family-based association study to examine immunologically relevant polymorphisms of a candidate gene, the vitamin D receptor, in conjunction with three measures of TB status in two Native Paraguayan populations, the Aché and the Avá. This is the first large-scale genetic analysis of Native South Americans to examine susceptibility to both infection and disease following exposure to M. tuberculosis. These two types of susceptibility reflect differences in innate and acquired immunity that have proven difficult to elucidate in other populations. Our results indicate that among the Aché, the FokI F allele protects individuals from infection, while the TaqI t allele protects against active disease but not infection. In particular, FF homozygotes are 17 times more likely to test positive for exposure to TB, but no more likely to have ever been diagnosed with active TB. TT individuals are 42 times less likely to mount a delayed-type hypersensitivity response, and the T allele was significantly more likely to have been transmitted to offspring who have been diagnosed with active TB. This ongoing research is of vital importance to indigenous groups of the Americas, because if there is a population-specific component to TB susceptibility, it will likely prove most effective to incorporate this into future treatment and prevention strategies.     

Vitamin D receptor gene polymorphisms and sputum conversion time in pulmonary tuberculosis patients

A cohort of pulmonary tuberculosis (TB) patients in a South African admixed population was investigated to determine if the vitamin D receptor gene (VDR) polymorphisms FokI, ApaI, and TaqI are associated with TB susceptibility or time to sputum conversion, and to investigate other clinical and demographic factors affecting the rate of response to treatment. Firstly, a case-control association study of 249 TB cases and 352 healthy controls was carried out to investigate association of VDR polymorphisms with TB susceptibility. Secondly, a cohort of pulmonary tuberculosis patients with conversion times for both sputum smear (n=220) and culture (n=222) were analysed to determine factors contributing to mycobacterial resolution in sputum. Age and gender adjusted Cox regression models were constructed. Our results indicate that the extent of disease at diagnosis was predictive of both smear and culture conversion times in the final models. Smoking status and VDR genotype contributed independently to smear conversion time, with ApaI 'AA' genotype and TaqI 'T'-containing genotypes predictive of a faster response to TB chemotherapy. We did not find an association between VDR genotype and TB in the case-control study. We conclude that the time taken for an individual to convert to sputum negativity while on antituberculosis therapy can be independently predicted by the VDR genotype.     

Vitamin D

Vitamin D evolved for the development and maintenance of a healthy vertebrate skeleton. Vitamin D (1,25-dihydroxyvitamin D) maintains serum calcium and phosphorus levels in a physiologic range for skeleton mineralization. Vitamin D increases intestinal calcium absorption, stimulating osteoblast function and mobilizing osteoclast precursor cells to enhance bone calcium mobilization. Most vitamin D for the human requirement comes from exposure to sunlight. Sunscreen use, aging, and an increase in latitude or skin pigmentation dramatically reduce the cutaneous synthesis of vitamin D₃. Vitamin D deficiency has been linked to increased risk of many chronic diseases, including diabetes, cancer, hypertension, and heart disease. There is strong evidence that vitamin D plays a role in immunomodulation, cellular proliferative activity regulation, and renin production downregulation. Thus, vigilance to prevent vitamin D deficiency by the measurement of serum 25-hydroxyvitamin D is important for overall health and well-being. Although the recommended adequate intake for vitamin D is 200, 400, and 600 international units (IUs) for ages 0–50, 51–70, and 71+ yr, respectively, in the absence of exposure to adequate sunlight, the requirement is at least 1000 IUs of vitamin D. Responsible sun exposure will guarantee vitamin D sufficiency. Eating and drinking foods fortified with vitamin D, such as milk and orange juice, also provides some of the vitamin D requirement.     

Vitamin D deficiency and changes in serum vitamin D levels with treatment among tuberculosis patients in South Korea

Background and objective: Vitamin D deficiency has been reported to be associated with the development of active tuberculosis (TB), but many discrepancies exist among studies. The aims of this study were to compare the frequency of vitamin D deficiency in a Korean population of TB patients and control subjects, and to monitor the changes in vitamin D levels during TB treatment. Methods: Patients with newly diagnosed TB were prospectively enrolled. In addition, healthy volunteers or patients with diseases other than TB were enrolled as controls. Baseline serum 25‐hydroxyvitamin D (25‐OHD) levels were measured in both groups and compared. In the TB patients, measurements of serum 25‐OHD were repeated 1 month after the initiation of treatment and again after completion of treatment. Results: In total, 116 patients with TB and 86 control subjects were recruited. The median 25‐OHD concentration was not different in TB patients at diagnosis (13.9 ng/mL; interquartile range (IQR) 8.80–21.8) compared with control subjects (13.2 ng/mL; IQR 9.6–19.3) (P = 0.97). The frequency of vitamin D deficiency (≤10 ng/mL) was also not different in TB patients (36.2%) compared with controls (27.3%) (P = 0.21). In TB patients, the median 25‐OHD concentration decreased significantly during treatment, to 12.5 ng/mL at 1 month and 11.0 ng/mL on completion of treatment (P = 0.01). Conclusions: Vitamin D levels do not appear to be associated with the development of TB in the Korean population. The median 25‐OHD concentration decreased after treatment for TB.     

Vitamin D and diabetes

There is no doubt that vitamin D deficiency is the cause of several metabolic bone diseases, but vitamin D status is also linked to many major human diseases including immune disorders. Mounting data strengthen the link between vitamin D and diabetes, in particular T1D and T2D. Despite some inconsistencies between studies that associate serum 25(OH)D levels with the risk of developing T1D or T2D, there seems to be an overall trend for an inverse correlation between levels of 25(OH)D and both disorders. There is also compelling evidence that 1,25(OH)2D regulates b-cell function by different mechanisms, such as influencing insulin secretion by regulating intracellular levels of Ca2+, increasing β-cell resistance to apoptosis, and perhaps also increasing β-cell replication. The capacity of vitamin D, more specifically 1,25(OH)2D, to modulate immune responses is of particular interest for both the therapy and prevention of diabetes. In the case of T1D, vitamin D supplementation in prediabetic individuals could help prevent or reduce the initiation of autoimmune processes possibly by regulating thymic selection of the T-cell repertoire, decreasing the numbers of autoreactive T cells, and inducing Treg cells. Although immune modulation is generally discussed for the treatment of T1D, it is also relevant for T2D. Indeed, recent studies have shown that T2D patients have increased systemic inflammation and that this state can induce β-cell dysfunction and death. Supplementation trials with regular vitamin D for the protection against the development of T1D and T2D have generated some contradictory data, but many weaknesses can be identified in these trials as most were underpowered or open-labeled. However, the overwhelming strength of preclinical data and of the observational studies make vitamin D or its analogues strong candidates for the prevention or treatment of diabetes or its complications. However, proof of causality needs well-designed clinical trials and if positive, adequate dosing, regimen, and compound studies are needed to define the contribution of vitamin D status and therapy in the global diabetes problem. There are many confounding factors that need to be taken into consideration when translating successful vitamin D therapies in animal models into humans, for example, gender, age, lifestyle, and genetic background. To come to solid conclusions on the potential of vitamin D or its analogues in the prevention of or therapy for all forms of diabetes, it is clear that large prospective trials with carefully selected populations and end points will be needed, but should also receive high priority.     

Vitamin D and diabetes

Vitamin D deficiency predisposes individuals to type 1 and type 2 diabetes, and receptors for its activated form—1,25-dihydroxyvitamin D₃—have been identified in both beta cells and immune cells. Vitamin D deficiency has been shown to impair insulin synthesis and secretion in humans and in animal models of diabetes, suggesting a role in the development of type 2 diabetes. Furthermore, epidemiological studies suggest a link between vitamin D deficiency in early life and the later onset of type 1 diabetes. In some populations, type 1 diabetes is associated with certain polymorphisms within the vitamin D receptor gene. In studies in nonobese diabetic mice, pharmacological doses of 1,25-dihydroxyvitamin D₃, or its structural analogues, have been shown to delay the onset of diabetes, mainly through immune modulation. Vitamin D deficiency may, therefore, be involved in the pathogenesis of both forms of diabetes, and a better understanding of the mechanisms involved could lead to the development of preventive strategies.     

Vitamin D and ageing

Within the past three to four decades a revolution has occurred in our understanding of vitamin D and its effects. Sundry laboratory and epidemiologic studies have revealed that the active metabolite of vitamin D controls and/or ameliorates various pathologies. As presented here, there is substantive evidence that vitamin D may play a positive and important role in the ageing process. This evidence arises from detailed consideration of various biological mechanisms and processes by which vitamin D operates as well as specific examples of its exerting control/amelioration of various human maladies which contribute to ageing. Arguments are advanced that vitamin D appears to play a major positive role in biogerontology by reducing susceptibility in the elderly to chronic degenerative diseases. It is strongly recommended that the positive role of vitamin D in ageing be taken into account by gerontologists and biogerontology researchers.     

维生素D和肥胖

大量研究表明维生素D及维牛素D受体(VDR)与肥胖密切相关.血清25(OH)D及1,25(OH),D的浓度都与体重指数(BMI)呈负相关.潜在的原因可能是由于肥胖者活动少及着装习惯导致的日光照射少以及大量的维生素D储存于脂肪组织中所致.研究发现,补充维生素D有利于减轻体重.因此,肥胖者比非肥胖者更需要补充维生素D.只有增加安全、合适的日照时间,食用强化维生素D的食品或者补充高剂量的维牛素D才能保证体内充足的维生素D水平.