Effects of Vitamin D and K on Interleukin-6 in COVID-19

BackgroundPathology during COVID-19 infection arises partly from an excessive inflammatory response with a key role for interleukin (IL)-6. Both vitamin D and K have been proposed as potential modulators of this process.MethodsWe assessed vitamin D and K status by measuring circulating 25-hydroxyvitamin D (25(OH)D) and desphospho-uncarboxylated Matrix Gla-Protein (dp-ucMGP), respectively in 135 hospitalized COVID-19 patients in relation to inflammatory response, elastic fiber degradation and clinical outcomes.ResultsComparing good and poor disease outcomes of COVID-19 patients, vitamin 25(OH)D levels were not significantly different. IL-6 levels, however, were significantly higher in patients with poor outcome, compared to patients with good outcome (30.3 vs. 153.0 pg/mL; p < 0.0001). Dp-ucMGP levels as biomarker of extrahepatic vitamin K status was associated with IL-6 levels (r = 0.35; p < 0.0001). In contrast, 25(OH)D levels were only borderline statistically significant correlated with IL-6 (r = −0.14; p <0.050). A significant association was also found between IL-6 and elastic fiber degradation. Contrary to vitamin K status, 25(OH)D did not correlate with elastic fiber degradation.ConclusionsDp-ucMGP associates with IL-6 as a central component of the destructive inflammatory processes in COVID-19. An intervention trial may provide insight whether vitamin K administration, either or not in combination with vitamin D, improves clinical outcome of COVID-19.

Exogenous Vitamin D3 Modulates Response of Bovine Macrophages to Mycobacterium avium subsp. paratuberculosis Infection and Is Dependent Upon Stage of Johne’s Disease

Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of ruminant enteritis, targets intestinal macrophages. During infection, macrophages contribute to mucosal inflammation and development of granulomas in the small intestine which worsens as disease progression occurs. Vitamin D3 is an immunomodulatory steroid hormone with beneficial roles in host-pathogen interactions. Few studies have investigated immunologic roles of 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in cattle, particularly cattle infected with MAP. This study examined the effects of exogenous vitamin D3 on immune responses of monocyte derived macrophages (MDMs) isolated from dairy cattle naturally infected with MAP. MDMs were pre-treated with ± 100 ng/ml 25(OH)D3 or ± 4 ng/ml 1,25(OH)2D3, then incubated 24 hrs with live MAP in the presence of their respective pre-treatment concentrations. Following treatment with either vitamin D3 analog, phagocytosis of MAP by MDMs was significantly greater in clinically infected animals, with a greater amount of live and dead bacteria. Clinical cows had significantly less CD40 surface expression on MDMs compared to subclinical cows and noninfected controls. 1,25(OH)2D3 also significantly increased nitrite production in MAP infected cows. 1,25(OH)2D3 treatment played a key role in upregulating secretion of pro-inflammatory cytokines IL-1β and IL-12 while downregulating IL-10, IL-6, and IFN-γ. 1,25(OH)2D3 also negatively regulated transcripts of CYP24A1, CYP27B1, DEFB7, NOS2, and IL10. Results from this study demonstrate that vitamin D3 compounds, but mainly 1,25(OH)2D3, modulate both pro- and anti-inflammatory immune responses in dairy cattle infected with MAP, impacting the bacterial viability within the macrophage.

Association of serum 25-hydroxyvitamin D concentrations with risk of dementia among individuals with type 2 diabetes: A cohort study in the UK Biobank

Background Several epidemiological studies have suggested that vitamin D status is associated with risk of dementia in general populations. However, due to the synergistic effect between diabetic pathology and neuroinflammation, and the prothrombotic profile in patients with diabetes, whether vitamin D is associated with risk of dementia among patients with diabetes is unclear. This study aimed to investigate the associations of circulating vitamin D levels with risks of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VD) among adults with type 2 diabetes (T2D). Methods and findings This study included 13,486 individuals (≥60 years) with T2D and free of dementia at recruitment (2006–2010) from the UK Biobank study. Serum 25-hydroxyvitamin D (25[OH]D) concentrations were measured using the chemiluminescent immunoassay method at recruitment. Serum 25(OH)D ≥ 75 nmol/L was considered sufficient, according to the Endocrine Society Clinical Practice Guidelines. Incidence of all-cause dementia, AD, and VD cases was ascertained using electronic health records (EHRs). Each participant’s person-years at risk were calculated from the date of recruitment to the date that dementia was reported, date of death, date of loss to follow-up, or 28 February 2018, whichever occurred first. Among the 13,486 individuals with T2D (mean age, 64.6 years; men, 64.3%), 38.3% had vitamin D ≥ 50 nmol/L and only 9.1% had vitamin D ≥ 75 nmol/L. During a mean follow-up of 8.5 years, we observed 283 cases of all-cause dementia, including 101 AD and 97 VD cases. Restricted cubic spline analysis demonstrated a nonlinear relationship between serum 25(OH)D and risk of all-cause dementia (Pnonlinearity < 0.001) and VD (Pnonlinearity = 0.007), and the nonlinear association reached borderline significance for AD (Pnonlinearity = 0.06), with a threshold at around a serum 25(OH)D value of 50 nmol/L for all the outcomes. Higher serum levels of 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD. The multivariate hazard ratios and 95% confidence intervals for participants who had serum 25(OH)D ≥ 50 nmol/L, compared with those who were severely deficient (25[OH]D < 25 nmol/L), were 0.41 (0.29–0.60) for all-cause dementia (Ptrend < 0.001), 0.50 (0.27–0.92) for AD (Ptrend = 0.06), and 0.41 (0.22–0.77) for VD (Ptrend = 0.01). The main limitation of the current analysis was the potential underreporting of dementia cases, as the cases were identified via EHRs. Conclusions In this study, we observed that higher concentrations of serum 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD among individuals with T2D. Our findings, if confirmed by replication, may have relevance for dementia prevention strategies that target improving or maintaining serum vitamin D concentrations among patients with T2D.

Vitamin D Status and SARS-CoV-2 Infection in a Cohort of Kidney Transplanted Patients

Background: Recently the protective role of 25-hydroxyvitamin D (25(OH)D) against viral infections has been hypothesized. We evaluated the association between vitamin D status and SARS-CoV-2 infection susceptibility and severity in a cohort of kidney transplanted patients (KTxp). Methods: A total of 61 KTxp with SARS-CoV-2 infection (COV+) were matched with 122 healthy KTxp controls (COV−). Main biochemical parameters at 1, 6, and 12 months before SARS-CoV-2 infection were recorded. Vitamin D status was considered as the mean of two 25(OH)D measures obtained 6 ± 2 months apart during the last year. The severity of SARS-CoV-2 infection was based on the need for hospitalization (HOSP+) and death (D+). Results: 25(OH)D levels were lower in COV+ than in controls [19(12–26) vs. 23(17–31) ng/mL, p = 0.01]. No differences among the other biochemical parameters were found. The SARS-CoV-2 infection discriminative power of 25(OH)D was evaluated by ROC-curve (AUC 0.61, 95% CI 0.5–0.7, p = 0.01). 25(OH)D was not significantly different between HOSP+ and HOSP− [17(8–25) vs. 20(15–26) ng/mL, p = 0.19] and between D+ and D− [14(6–23) vs. 20(14–26) ng/mL, p = 0.22] and had no significant correlation with disease length. Conclusions: During the year preceding the infection, 25(OH)D levels were lower in COV+ KTxp in comparison with controls matched for demographic features and comorbidities. No significant association between vitamin D status and SARS-CoV-2 infection related outcomes was found.

Intra-trial mean 25(OH)D and PTH levels and risk of falling in older men and women in the Boston STOP IT trial

Context Supplementation with vitamin D has the potential to both reduce and increase risk of falling, and parathyroid hormone (PTH) may contribute to fall risk. Objective To assess the associations of intra-trial mean circulating levels of 25-hydroxyvitamin D [25(OH)D] and PTH on incident falls in healthy older adults. Design Observational within a clinical trial. Setting The Bone Metabolism Laboratory at the USDA Nutrition Center at Tufts University. Participants 410 men and women age 65 years and older who participated in the 3-year Boston STOP IT trial to determine the effect of supplementation with 700 IU of vitamin D3 plus calcium on incident falls (secondary endpoint). Intra-trial exposures of 25(OH)D and PTH were calculated as the mean of biannual measures up to and including the first fall. Main outcome measures: incidence of first fall Results Intra-trial mean 25(OH)D was significantly associated with risk of falling in a U-shaped pattern; the range associated with minimal risk of falling was approximately 20-40 ng/ml. PTH was not significantly associated with risk of falling. Conclusions The findings highlight the importance of maintaining the circulating 25(OH)D level between 20 and 40 ng/ml, the range that is also recommended for bone health. At PTH levels within the normal range, there was no detectible independent association of PTH with fall risk.

Serum 25-Hydroxyvitamin D and the risk of breast cancer in women from Southern Morocco: A case-control study

OBJECTIVES: Assessing Vitamin-D status and checking if low serum 25(OH)D is a factor in breast cancer (BC) for Southern Moroccan women. MATERIALS/METHODS: Study conducted in Morocco about women with BC (n = 90) and controls (n = 90). 25-hydroxy-vitamin-D Biological analyzes executed during the first consultation. Social data and anthropometric parameters were collected for all participants. RESULTS: These women constituted 67.78 % for the cases and 85.6% for the controls. The average age was 48.72±9.71 (cases) and 46.40±12.52 (controls). We found that 53.33% of cases and 40% of controls were postmenopausal and that hypovitaminosis-D affected 80 and 64.4% of cases and controls, respectively. Statistical analysis showed that hypovitaminosis-D was a significative risk factor for BC in Southern Moroccan women. The Odds Ratio was of 5 (p < 0.0001). The BC subtypes had Odds Ratios greater than 1. The highest value was obtained with Luminal B subtype (Odds ratio = 6.25; p = 0.0007). CONCLUSION: This study reinforces the evidence implicating hypovitaminosis-D among modifiable risk factors for BC. Further studies are needed to assess the extent of hypovitaminosis-D in Moroccan women with BC.

Relationship between serum 25-hydroxyvitamin D and target organ damage in children with essential hypertension

Researchers have shown that 25-hydroxyvitamin D (25[OH] D), a kind of active vitamin D in the human body, plays a role in cardiovascular disease (CVD). Low serum 25(OH) D levels have been found to be associated with elevated blood pressure (BP) in adults. However, measurement of 25(OH) D in hypertensive children has not been documented. The aim of this study was to investigate the relationship between 25(OH) D and target organ damage (TOD) in children with essential hypertension. We recruited a total of 346 children with essential hypertension and analyzed the correlation between serum 25(OH) D and TOD. Serum 25(OH) D concentration was significantly lower in the TOD than in the no-TOD group (t = 2.416, P = 0.016), as well as significantly lower in the two-organ damage than in the single-organ damage group (t = 3.140, P = 0.002). Pearson’s correlation coefficient (PCC) indicated that serum 25(OH) D levels were negatively correlated with left ventricular mass index (LVMI; r = −0.110, P = 0.041) and albuminuria (r = −0.120, P = 0.026). Linear- regression analysis showed that 25(OH) D was a risk factor for left ventricular hypertrophy (LVH; β ± s.e. =−0.074 ± 0.036; 95% confidence interval [CI], − 0.145 to –0.003; P < 0.001) and renal damage (β ± s.e.= −0.018 ± 0.008; 95% CI, − 0.035 to –0.002; P = 0.004). In total, our data revealed that serum 25(OH) D was independently associated with hypertensive cardiac and renal damage, meaning that it was a risk factor for LVH and albuminuria in childhood hypertension.

Serum Vitamin D as a Biomarker in Autoimmune, Psychiatric and Neurodegenerative Diseases

Vitamin D is a steroid hormone regulating calcium-phosphorus homeostasis, immune response and brain function. In the past thirty years, an increasing number of cohort studies, meta-analyses and randomized controlled trials (RTCs) evaluated the serum levels of 25-hydroxyvitamin D [25(OH)D], which is considered the Vitamin D status biomarker, in patients affected by neurological, psychiatric and autoimmune diseases. Although an association between low 25(OH)D serum levels and the prevalence of these diseases has been found, it is still unclear whether the serum 25(OH)D measurement can be clinically useful as a biomarker for diagnosis, prognosis and predicting treatment response in neurodegeneration, mental illness and immune-mediated disorders. The lack of standardized data, as well as discrepancies among the studies (in the analytical methods, cut-offs, endpoints and study sets), weakened the findings achieved, hindered pooling data, and, consequently, hampered drawing conclusions. This narrative review summarizes the main findings from the studies performed on serum 25(OH)D in neurological, psychiatric and autoimmune diseases, and clarifies whether or not serum 25(OH)D can be used as a reliable biomarker in these diseases.

Possibilities of colecalciferol therapy for tension type headache combined with hypovitaminosis D

Introduction. Modern studies indicate the therapeutic effect of vitamin D (VD) in chronic pain conditions, but there is no data on the use of VD in chronic tension type headache (CTTH) treatment.Objective: comparative evaluation of the effectiveness of various options for preventive treatment of CTTH: the use of colecalciferol, standard therapy of the disease and a combination of these methods.Materials and methods. 125 women with CTTH and hypovitaminosis D were treated in the study. The frequency, duration and intensity of headache (HF, HD and HI, respectively), HIT index, frequency of analgesics taking, pericranial muscle dysfunction were evaluated. The VD level was measured by the concentration of 25-hydroxyvitamin D [25(OH)D]. The patients received differentiated therapy for 16 weeks: group 1 – colecalciferol, group 2 – amitriptyline, group 3 – a combination of these medicines. Results. In group 1, HF, HD, HIT-index and the frequency of analgesics taking decreased, all p ≤ 0.001. In groups 2 and 3, the values of all CTTH-parameters decreased, all p < 0.05. HF, HIT-index and the frequency of analgesics taking in group 3 decreased more than in group 2, all p >< 0.017. In women who had VD deficiency before treatment, the decrease in HF from the initial one was 36% in group 1, 55% in group 2, and 74% in group 3. In patients who had VD deficiency before treatment, the effectiveness of therapy in group 3 was higher than in group 2: 74% vs. 55%, respectively, p >< 0.001.Conclusions. Treatment of hypovitaminosis D in women with CTTH is accompanied by a decrease in HF, the effect of headache on the quality of life of patients and the frequency of taking analgesics. In CTTH and VD deficiency normalization of 25(OH)D level contributes to higher efficiency of standard therapy.

Persistent hypercobalaminemia three months after successful gradual attenuation of extrahepatic shunts in dogs: a prospective cohort study

Background Deficiencies in vitamin A and D and disorders in the vitamin B complex are often present in people with chronic liver diseases. So far, the serum concentrations of these vitamins have not yet been studied in dogs with congenital extrahepatic portosystemic shunts (EHPSS), who also have some degree of liver dysfunction. The objective was to assess serum vitamin concentrations in dogs with EHPSS from diagnosis to complete closure. A prospective cohort study was performed using ten client-owned dogs with EHPSS, closed after gradual surgical attenuation. Serum concentrations of vitamin A, 25-hydroxyvitamin D, folic acid, cobalamin and methylmalonic acid (MMA) were measured at diagnosis prior to institution of medical therapy, prior to surgery, and three months after gradual attenuation and complete closure of the EHPSS. Results At diagnosis, median serum concentrations of vitamin A, 25-hydroxyvitamin D and folic acid were 18.2 μg/dL (8.8 - 79.5 μg/dL), 51.8 ng/mL (19.4 - 109.0 ng/mL), and 8.1 μg/L (5.2 - 14.5 μg/L), respectively, which increased significantly postoperatively (88.3 μg/dL (51.6 - 182.2 μg/dL, P=0.005), 89.6 ng/mL (49.3 - >150.0 ng/mL, P =0.005), and 14.8 μg/L (11.5 - 17.7 μg/L, P <0.001), respectively). Median serum cobalamin concentrations were 735.5 ng/L (470 - 1388 ng/L) at diagnosis and did not significantly decrease postoperatively (P =0.122). Both at diagnosis and three months postoperatively 7/10 dogs had hypercobalaminemia. Conclusions Serum concentrations of vitamin A, 25-hydroxyvitamin D and folic acid significantly increase after surgical attenuation. Nevertheless, persistent hypercobalaminemia is suggestive of ongoing liver dysfunction, despite successful surgery.