Background/objectivesVitamin K and D co-treatment may have additive effects on bone and cardiovascular health and is frequently used as an over-the-counter supplement. The primary aim of this study was to assess whether the effect of vitamin D supplementation on bone turnover markers and cardiovascular parameters is modified according to vitamin K status at baseline (i.e., serum levels of vitamin K1, MK4 and MK7).MethodsThis is a post-hoc analysis of a randomized controlled vitamin D supplementation (2,800 international units daily for 8 weeks) trial in 200 participants. We measured vitamin K1, MK4 and MK7 by means of the currently available gold standard liquid chromatography tandem mass spectrometric and analysed cardiovascular and bone markers (including 24-h systolic and diastolic blood pressure, glucose and lipid parameters as well as osteocalcin, beta-crosslaps, and procollagen type 1 N-terminal propeptide). The main aim was to analyze whether pre-intervention vitamin K status (moderator) influenced the effects of vitamin D supplementation on outcome measures of bone and cardiovascular health after the intervention (moderation analyses). We also investigated whether vitamin D supplementation effects vitamin K status and whether vitamin K measures correlated with the outcome parameters.ResultsModeration analyses showed no significant interaction between vitamin K status and the intervention (vitamin D supplementation/placebo) on cardiovascular or bone parameters. We observed no treatment effect of vitamin D on vitamin K status. In exploratory analyses, parameters of vitamin K status correlated only weakly and inconsistently with some bone and cardiovascular parameters.ConclusionThe data from this post-hoc analysis do not provide evidence for the assumption that vitamin K status modifies or enhances effects of vitamin D supplementation on cardiovascular or bone parameters. These findings are in line with current guidelines, which do not routinely recommend vitamin K and D co-treatment in patients with osteoporosis. However, further trials are needed to evaluate the potential benefits of vitamin K supplementation and its combination with vitamin D.

It has been assumed that magnesium (Mg) status may interact with vitamin D status. We therefore aimed at investigating the association between Mg and vitamin D status in a large cohort of adult individuals with a high prevalence of deficient/insufficient vitamin D and Mg status. We used data from the Ludwigshafen Risk and Cardiovascular Health Study (n = 2,286) to analyze differences according to serum Mg status in circulating 25-hydroxyvitamin D [25(OH)D] (primary endpoint), 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], vitamin D metabolite ratio and calcitriol, and odds ratios for deficient or insufficient 25(OH)D (secondary endpoints). We performed unadjusted and risk score (RS) adjusted and matched analyses. Of the study cohort (average age > 60 years), one third was 25(OH)D deficient (< 12 ng/mL), one third 25(OH)D insufficient (12 to < 20 ng/mL), about 10

Circulating calcitriol may contribute to the risk of cardiovascular disease (CVD), but its regulation in patients with CVD is poorly characterized. We therefore aimed to assess determinants of circulating calcitriol in these patients. We analyzed 2183 independent samples from a large cohort of patients scheduled for coronary angiography and 1727 independent samples from different other cohorts from patients with a wide range of CVDs, including heart transplant candidates, to quantify the association of different parameters with circulating calcitriol. We performed univariable and multivariable linear regression analyses using the mathematical function that fitted best with circulating calcitriol. In the multivariable analysis of the large single cohort, nine parameters remained significant, explaining 30.0% (32.4% after exclusion of 22 potential outliers) of the variation in circulating calcitriol (r=0.548). Log-transformed 25-hydroxyvitamin D [25(OH)D] and log-transformed glomerular filtration rate were the strongest predictors, explaining 17.6% and 6.6%, respectively, of the variation in calcitriol. In the analysis of the combined other cohorts, including heart transplant candidates, the multivariable model explained a total of 42.6% (46.1% after exclusion of 21 potential outliers) of the variation in calcitriol (r=0.653) with log-transformed fibroblast growth factor-23 and log-transformed 25(OH)D explaining 29.0% and 6.2%, respectively. Circulating 25(OH)D was positively and FGF-23 inversely associated with circulating calcitriol. Although significant, PTH was only a weak predictor of calcitriol in both analyses (<2.5%). In patients with CVD, FGF-23 and 25(OH)D are important independent determinants of circulating calcitriol. The relative importance of these two parameters may vary according to CVD severity. Future studies should focus on the clinical importance of regulating circulating calcitriol by different parameters.

Objectives: The role of vitamin D deficiency in cardiovascular disease (CVD) is controversial. Inherent biological and analytical limitations compromise the specificity of widely used 25-hydroxyvitamin D [25(OH)D] cut-offs. Simultaneous determination of 25(OH)D and 24,25-dihydroxyvitamin D [24,25(OH)(2)D] permits a functional assessment of vitamin D metabolism. The present study compared the associations of functional vitamin D deficiency and low vitamin D reservoirs with CVD mortality and CVD burden. Methods: 25(OH)D, 24,25(OH)(2)D, the degree of coronary obstruction on angiography, high-sensitive cardiac troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP), and 10-year CVD mortality were obtained from 2,456 participants of the LURIC (Ludwigshafen Risk and Cardiovascular Health) study. Results: Neither low 25(OH)D concentrations nor functional vitamin D deficiency were associated with the number of atherosclerotic coronary arteries or the degree of coronary obstruction. Over a median follow-up of 9.9 years, 454 participants died (23.6 %) due to CVD. CVD mortality was doubled in individuals with 25(OH)D concentrations below the widely used cut-off for deficiency of <50 nmol/L [20 ng/mL] (21.6 vs. 11.5 %). In individuals with and without functional vitamin D deficiency, CVD mortality was 25.0 and 16.7 %, respectively. NT-proBNP and heart failure prevalence were also higher in vitamin D deficient individuals. Conclusions: Vitamin D deficient individuals have markedly higher CVD mortality, but only marginally higher hs-cTnT concentrations. A higher prevalence of heart failure and higher NT-proBNP concentrations suggest a link between vitamin D deficiency and cardiac function. The traditional and metabolic assessment of vitamin D status showed comparable associations for the different parameters of cardiac health.

OBJECTIVES:Vitamin D and K are believed to promote bone health, but existing evidence is controversial. This study aimed to measure several metabolites of both vitamins by liquid chromatography tandem mass spectrometry (LC-MS/MS) in a cohort of postmenopausal women with low and normal bone mineral density (BMD). METHODS:Vitamin metabolites (25-hydroxyvitamin D (25[OH]D), 24,25-dihydroxyvitamin D (24,25(OH)2D), phylloquinone (K1), menaquinone-4 (MK-4) and MK-7) were measured in 131 serum samples by LC-MS/MS. The vitamin D metabolite ratio (VMR) was calculated. Parathyroid hormone (PTH), type I procollagen-N-terminal-peptide (PINP) and C-terminal telopeptides of type I collagen (CTX-I) were measured by immunoassay. Dual X-ray absorptiometry was performed to identify participants with normal (T-score>-1) and low (T-score<-1) BMD. RESULTS:Mean age was 58.2±8.5 years. BMD was normal in 68 and low in 63 women. Median (interquartile range) for 25(OH)D and total vitamin K concentrations were 53.5 (39.6-65.9) nmol/L and 1.33 (0.99-2.39) nmol/L. All vitamin metabolites were comparable in individuals with normal and low BMD. Furthermore, BMD and trabecular bone score were comparable in participants with adequate and inadequate vitamin status (at least one criterion was met: 25(OH)D <50 nmol/L, 24,25(OH)2D <3 nmol/L, VMR <4 %, total vitamin K <0.91 nmol/L). PTH, but not PINP or CTX-I, was inversely correlated with 25(OH)D, 24,25(OH)2D and VMR. Synergistic effects between vitamin D and K were not observed. CONCLUSIONS:Vitamin D and K status is not related to BMD and trabecular bone quality in postmenopausal women. Inverse associations were only seen between vitamin D metabolites and PTH.

Circulating 25-hydroxyvitamin D (25(OH)D) is the generally accepted indicator of vitamin D status. Since hydroxylation of 25(OH)D to 24-25-dihydroxyvitamin D (24,25(OH)2D) is the first step of its catabolism, it has been suggested that a low 24,25(OH)D level and a low vitamin D metabolite ratio (VMR), i.e., 24,25(OH)2D divided by 25(OH)D, may indicate high vitamin D requirements and provide additional diagnostic information beyond serum 25(OH)D. We, therefore, evaluated whether the classification of “functional vitamin D deficiency”, i.e., 25(OH)D below 50 nmol/L, 24,25(OH)2D below 3 nmol/L and a VMR of less than 4%, identifies individuals who benefit from vitamin D supplementation. In participants of the Styrian Vitamin D Hypertension trial, a randomized controlled trial (RCT) in 200 hypertensive patients with serum 25(OH)D below 75 nmol/L, who received either 2.800 international units of vitamin D per day or placebo over 8 weeks, 51 participants had functional vitamin D deficiency. In these individuals, there was no treatment effect of vitamin D supplementation on various parameters of bone metabolism and cardiovascular risk except for a significant effect on parathyroid hormone (PTH) and expected changes in vitamin D metabolites. In conclusion, a low vitamin D metabolite profile did not identify individuals who significantly benefit from vitamin D supplementation with regard to bone markers and cardiovascular risk factors. The clinical significance of functional vitamin D deficiency requires further evaluation in large vitamin D RCTs.

Background and aims: Quinolinic acid (QA) is a metabolite of the kynurenine pathway, which is activated by inflammatory stimuli during viral infection. We investigated the role of QA in patients infected with SARS-CoV-2, particularly its prognostic value for survival.Methods: Overall, 104 unvaccinated inpatients were included, divided into a survival (N = 80) and a deceased group (N = 24). Plasma levels of tryptophan, kynurenine, QA, C-reactive protein (CRP) and procalcitonin (PCT) were measured on admission and after seven days. The QA/TRP ratio and the relative differences between the measurements for QA (QA-Diff) and QA/TRP (Diff-QA/TRP) were calculated.Results: Among the kynurenine pathway markers, QA-Diff showed the highest discriminatory power for the survival prognosis (Youden index 0.467, cut-off-1.3 %, AUC 0.733, p < 0.001, sensitivity 0.79, specificity 0.675). Among the inflammatory markers, CRP showed the highest discriminatory power (Youden index 0.533, cut-off 25.0 mg/L, AUC 0.794, p < 0.001, sensitivity 0.958, specificity 0.575). A significant correlation between QA and PCT was found on admission and after one week (Spearman's rho 0.455 and 0.539, all p-values < 0.001).Conclusions: QA may serve as prognostic marker for survival in patients with SARS-CoV-2. The repeated measurements during the first week of the disease may enhance the prognostic power.

Recent evidence on the association between vitamin D and cognition in mentally healthy individuals is inconsistent. Furthermore, the link between vitamin D and cognitive ability in individuals with bipolar disorder has not been studied yet. Thus, we aimed to investigate the association between 25-hydroxyvitamin D (25(OH)D), 24,25 dihydroxyvitamin D (24,25(OH)2D, the vitamin D metabolite ratio (VMR) and cognition in a cohort of euthymic patients with bipolar disorder. Vitamin D metabolites were measured simultaneously by liquid-chromatography tandem mass-spectrometry in serum samples from 86 outpatients with bipolar disorder and 93 healthy controls. Neither the inactive precursor 25(OH)D, nor the primary vitamin D catabolite 24,25(OH)2D, or the vitamin D metabolite ratio were significantly associated with the domains “attention”, “memory”, or “executive function” in individuals with bipolar disorder and healthy controls. Further, no vitamin D deficiency effect or interaction group × vitamin D deficiency was found in the cognitive domain scores. In summary, the present study does not support vitamin D metabolism as a modulating factor of cognitive function in euthymic BD patients. Considering the current study’s cross-sectional design, future research should expand these results in a longitudinal setting and include additional aspects of mental health, such as manic or depressive symptoms, long-term illness course and psychopharmacological treatment.

Bone is a metabolically active endocrine organ that plays a central role in calcium and phosphate homeostasis.Parathyroid hormone, sex hormones and vitamin D are key regulators of bone metabolism.Bone turnover markers, such as bone alkaline phosphatase (BALP), procollagen type-1 N-terminal propeptide (P1NP), and carboxy-terminal collagen type-1 crosslinks (CTX-1) are widely used bone turnover markers that are useful to identify abnormalities in bone metabolism, but are unspecific for the underlying diseases.Through selected clinical cases, the utility and appropriate use of these markers will be illustrated.Furthermore, recent advances in the measurement of vitamin D metabolites by LC-MS/MS allow a functional assessment of vitamin D metabolism.A series of vitamin D-related cases will illustrate how the parallel measurement of 25-hydroxyvitamin D (25[OH]D) and 24,24-dihydroxyvitamin D (24,25[OH]2D) by modern LC-MS/MS methods enhances diagnostic possibilities and mitigates common analytical limitations.

Different foods, especially mushrooms, are a valuable source of vitamin D2. However, published concentrations in mushrooms show large variabilities. One reason for this is certainly the high biological variability caused by growth conditions, and another could also be found in the analytical methodology. Therefore, this study aimed to develop a sensitive and highly selective two-dimensional liquid chromatography mass spectrometry (LC–MS/MS) method for vitamin D2 analysis in mushrooms. After validation, the method was applied to four different mushroom species. The developed method with a one-step extraction procedure showed a limit of detection of 0.01 µg vitamin D2/g dry mass (DM), a limit of quantification of 0.05 µg vitamin D2/g DM, and recovery rates between 87.6 and 94.8