Several studies found an inverse relationship between 25-hydroxyvitamin D [25(OH)D] and markers of inflammation. A controversy exists as to whether vitamin D lowers inflammation or whether inflammation lowers 25(OH)D concentrations. Certainly 25(OH)D concentrations fall after major surgery. However, is this due to inflammation lowering 25(OH)D or is 25(OH)D being metabolically cleared by the body to quell inflammation. We searched the literature and found 39 randomized controlled trials (RCT) of vitamin D and markers of inflammation. Seventeen found significantly reduced inflammatory markers, 19 did not, one was mixed and one showed adverse results. With few exceptions, studies in normal subjects, obesity, type 2 diabetics, and stable cardiovascular disease did not find significant beneficial effects. However, we found that 6 out of 7 RCTS of vitamin D3 in highly inflammatory conditions (acute infantile congestive heart failure, multiple sclerosis, inflammatory bowel disease, cystic fibrosis, SLE, active TB and evolving myocardial infarction) found significant reductions. We found baseline and final 25(OH)D predicted RCTs with significant reduction in inflammatory markers. Vitamin D tends to modestly lower markers of inflammation in highly inflammatory conditions, when baseline 25(OH)D levels were low and when achieved 25(OH)D levels were higher. Future inquiries should: recruit subjects with low baseline 25(OH)D levels, subjects with elevated markers of inflammation, subjects with inflammatory conditions, achieve adequate final 25(OH)D levels, and use physiological doses of vitamin D. We attempted to identify all extant randomized controlled trials (RCTs) of vitamin D that used inflammatory markers as primary or secondary endpoints.

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Vitamin D and inflammation

Vitamin D is a key hormone involved in the regulation of calcium/phosphorous balance and recently it has been implicated in the pathogenesis of sub-inflammation, insulin resistance and obesity. The two main forms of vitamin D are cholecalciferol (Vitamin D3) and ergocalciferol (Vitamin D2): the active form (1,25-dihydroxyvitamin D) is the result of two hydroxylations that take place in liver, kidney, pancreas and immune cells. Vitamin D increases the production of some anti-inflammatory cytokines and reduces the release of some pro-inflammatory cytokines. Low levels of Vitamin D are also associated with an up-regulation of TLRs expression and a pro-inflammatory state. Regardless of the effect on inflammation, Vitamin D seems to directly increase insulin sensitivity and secretion, through different mechanisms. Considering the importance of low grade chronic inflammation in metabolic syndrome, obesity and diabetes, many authors hypothesized the involvement of this nutrient/hormone in the pathogenesis of these diseases. Vitamin D status could alter the balance between pro and anti-inflammatory cytokines and thus affect insulin action, lipid metabolism and adipose tissue function and structure. Numerous studies have shown that Vitamin D concentrations are inversely associated with pro-inflammatory markers, insulin resistance, glucose intolerance and obesity. Interestingly, some longitudinal trials suggested also an inverse association between vitamin D status and incident type 2 diabetes mellitus. However, vitamin D supplementation in humans showed controversial effects: with some studies demonstrating improvements in insulin sensitivity, glucose and lipid metabolism while others showing no beneficial effect on glycemic control and on inflammation. In conclusion, although the evidences of a significant role of Vitamin D on inflammation, insulin resistance and insulin secretion in the pathogenesis of obesity, metabolic syndrome and type 2 diabetes, its potential function in treatment and prevention of type 2 diabetes mellitus is unclear. Encouraging results have emerged from Vitamin D supplementation trials on patients at risk of developing diabetes and further studies are needed to fully explore and understand its clinical applications.

Vitamin D, sub-inflammation and insulin resistance. A window on a potential role for the interaction between bone and glucose metabolism

The objective of this systematic review was to assess the effect of vitamin D supplementation on selected inflammatory biomarkers in obese and overweight subjects. The search process was based on the selection of publications (DB-RCT and RCT) listed in the following databases: PubMed, Web of Knowledge, Scopus, the Cochrane Library and Embase. To assess the study quality, a nine-point scoring system according to the Newcastle–Ottawa scale was used, and a high-quality study was defined by a threshold of ≥7 points. Thirteen randomized controlled trials were included. The analysed population consisted of 1955 overweight and obese subjects. The mean age ranged from 13.6 to 71.7 years. Changes in the concentration of 25-hydroxycholecalciferol (25(OH)D), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were assessed. To combine individual study results, a meta-analysis was performed. The baseline levels of 25(OH)D suggested vitamin D deficiency or insufficiency in the analysed population. The vitamin D supplementation did not influence on CRP (std. mean differences −0.11; 95 % CI −0.27–0.04; p = 0.15), TNF-α (std. mean differences −0.13; 95 % CI −0.38–0.12; p = 0.31) and IL-6 concentrations (std. mean differences 0.1; 95 % CI −0.43–0.63; p = 0.71). This meta-analysis suggests that supplementation with vitamin D does not have a significant influence on changes in the concentration of selected inflammatory biomarkers in the obese and overweight subjects.

The effect of vitamin D supplementation on selected inflammatory biomarkers in obese and overweight subjects: a systematic review with meta-analysis

The prevalence of Vitamin D deficiency is increasing worldwide, which has be shown to be associated with increased risk of cardiovascular disease (CVD), autoimmune disease, and metabolic syndrome. These conditions are also associated with a heightened state of inflammation. The aim of the current study was to evaluate the effect of vitamin D supplementation on serum C-Reactive Protein (CRP) level and Neutrophil-to-lymphocyte ratio (NLR) distribution in a large cohort of adolescent girls. A total of 580 adolescent girls were recruited follow by evaluation of CRP and hematological parameters before and after supplementation with vitamin D supplements as 9 of 50000 IU cholecalciferol capsules for 9 weeks taken at weekly intervals. At baseline, serum hs-CRP level was 0.9 (95%CI: 0.5-1.8), while this value after intervention was reduced to 0.8 (95%CI: 0.3-1.6; P = 0.007). Similar results were also detected for NLR (e.g., NLR level was 1.66 ± 0.72 and 1.53 ± 0.67, P = 0.002, before and after therapy with compliance rate of >95.2%). Moreover, we found an association between hs-CRP and BMI, triglyceride, white blood cell count, and lymphocytes. Interestingly we observed a significant reduction in neutrophil count and CRP level after high dose vitamin D supplementation. Our findings showed that the high dose supplementation of vitamin D affects measures of systemic inflammation: reductions in High Sensitivity C-Reactive Protein level and Neutrophil-to-lymphocyte ratio (NLR) distribution. J. Cell. Biochem. 118: 4317-4322, 2017. © 2017 Wiley Periodicals, Inc.

High Dose Supplementation of Vitamin D Affects Measures of Systemic Inflammation: Reductions in High Sensitivity C-Reactive Protein Level and Neutrophil to Lymphocyte Ratio (NLR) Distribution.

Background: Vitamin D has recently attracted attention because reduced levels are associated with the prevalence and aggressiveness of several cancers. This study aimed to evaluate the relationship between preoperative serum 25 hydroxyvitamin D (25(OH) vitamin D) levels and clinicopathologic characteristics in female patients with papillary thyroid cancer (PTC). Methods: A total of 548 female patients who underwent total thyroidectomy for PTC between June 2012 and May 2013 were included. Blood samples were obtained within two weeks prior to surgery. Patients were categorized into four quartiles by preoperative serum 25(OH) vitamin D levels. The clinicopathologic features of PTC were analyzed retrospectively. Results: Preoperative 25(OH) vitamin D was significantly lower in patients with a tumor size of >1 cm (p=0.041) or lymph node metastasis (LNM; p=0.043). No significant trends in several clinicopathologic features were observed in relation to increasing serum vitamin D concentrations except decreasing ...

Low Serum 25 Hydroxyvitamin D Is Associated with Poor Clinicopathologic Characteristics in Female Patients with Papillary Thyroid Cancer

In vitro studies and some clinical studies suggest that vitamin D plays an important role in reducing inflammation. The objective of this review was to examine recent evidence that vitamin D status influences the level of inflammation in adults without acute illness or injury. Five large cross-sectional studies and two randomized controlled trials are the focus of this review. Associations between 25-hydroxyvitamin D (25OHD) and inflammation markers are significant and inverse in study populations with low 25OHD levels (<21 ng/mL). They are also inverse in adults with relatively high inflammation levels. These associations in the few available randomized controlled vitamin D intervention trials have been null; this may be because they were not examined in populations with sufficiently low levels of 25OHD or high levels of inflammation.

Ability of vitamin D to reduce inflammation in adults without acute illness.

endoscopic findings suggesting CD were observed in 66.6% of the participants, as other authors have described (Table 1). There are few case reports linking CD to peptic disease. In the present study, peptic ulcers were detected in 21.4% of the patients, all were positive for Helicobacter pylori. Two patients died from myocardial infarction after CD treatment; the effect of a GFD on cardiovascular risk factors needs to be better understood. In conclusion, CD is present in older Brazilians, in whom diagnosis is often delayed, leading to repercussions in their nutritional state. Tumors are generally presumed to cause weight loss and weakness in older adults, leading to some being investigated using invasive methods, without physicians considering the possibility of CD. Because a GFD improves well-being, physicians must be alert to the diagnosis of CD in patients aged 60 and older.

https://agsjournals.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1532-5415.2011.03516.x

Perception of health students about older adults in Brazil.

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Ability of vitamin D to reduce inflammation in adults without acute illness.

Perception of health students about older adults in Brazil.