•High throughput LC–MS/MS method to measure multiple vitamin D metabolites in serum.•SLE is an effective sample preparation method for multiple vitamin D metabolites.•Chiral column separation ...improves resolution between identical mass to charges.•Routine serum analysis shows correlations between active and inactive metabolites.
Recent studies suggest that vitamin D-deficiency is linked to increased risk of common human health problems. To define vitamin D ‘status’ most routine analytical methods quantify one particular vitamin D metabolite, 25-hydroxyvitamin D3 (25OHD3). However, vitamin D is characterized by complex metabolic pathways, and simultaneous measurement of multiple vitamin D metabolites may provide a more accurate interpretation of vitamin D status.
To address this we developed a high-throughput liquid chromatography-tandem mass spectrometry (LC–MS/MS) method to analyse multiple vitamin D analytes, with particular emphasis on the separation of epimer metabolites. A supportive liquid-liquid extraction (SLE) and LC–MS/MS method was developed to quantify 10 vitamin D metabolites as well as separation of an interfering 7α-hydroxy-4-cholesten-3-one (7αC4) isobar (precursor of bile acid), and validated by analysis of human serum samples.
In a cohort of 116 healthy subjects, circulating concentrations of 25-hydroxyvitamin D3 (25OHD3), 3-epi-25-hydroxyvitamin D3 (3-epi-25OHD3), 24,25-dihydroxyvitamin D3 (24R,25(OH)2D3), 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3), and 25-hydroxyvitamin D2 (25OHD2) were quantifiable using 220μL of serum, with 25OHD3 and 24R,25(OH)2D3 showing significant seasonal variations.
This high-throughput LC–MS/MS method provides a novel strategy for assessing the impact of vitamin D on human health and disease.
Adequate intakes of fat-soluble vitamins are essential to support the growth and development of the foetus, the neonate, and the young child. By means of an online self-administered frequency ...questionnaire, this study aimed to evaluate the intake of vitamins A, D, E, and K in Belgian infants (
= 455), toddlers (
= 265), pregnant women (
= 161), and lactating women (
= 165). The contribution of foods, fortified foods, and supplements on the total intake was quantified. 5% of toddlers, 16% of pregnant women, and 35% of lactating women had an inadequate vitamin A intake. Conversely, excessive vitamin A intakes were associated with consumption of liver (products). Furthermore, 22% of infants were at risk for inadequate vitamin D intake due to the lack of prophylaxis, while consumption of highly dosed supplements posed a risk for excessive intakes in 6%-26% of infants. Vitamin D intake in pregnant women and lactating women was inadequate (median of 51%, respectively, 60% of the adequate intake). In all groups, the risk for inadequate intake of vitamin E and K was low. Contribution of fortified foods to vitamin A, D, E, and K intake was minor, except in toddlers. National fortification strategies should be investigated as an alternative or additional strategy to prevent vitamin D and A deficiency. There is a need to revise and set uniform supplement recommendations. Finally, non-users of vitamin D prophylaxis need to be identified for targeted treatment.
Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D 25(OH)D.
...The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans.
The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials.
A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation.
This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3) could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.
BACKGROUND: Cystic fibrosis (CF) with pancreatic insufficiency is associated with poor absorption of fat and fat-soluble vitamins, including vitamin D. Pancreatic enzyme supplementation does not ...completely correct fat malabsorption in CF patients. OBJECTIVE: The objective of the study was to compare the vitamin D status of children, adolescents, and young adults with CF who were treated with routine vitamin D and pancreatic enzyme supplements with the vitamin D status of a healthy reference group from a similar geographic area. DESIGN: Growth, dietary intake, and serum concentrations of 25-hydroxyvitamin D 25(OH)D, 1,25-dihydroxyvitamin D 1,25(OH)₂D, and parathyroid hormone (PTH) were measured in 101 white subjects with CF and a reference group of 177 white subjects. RESULTS: The median daily vitamin D supplementation in the CF group was 800 IU. The mean ± SD serum concentrations of 25(OH)D were 20.7 ± 6.5 ng/mL in the CF group and 26.2 ± 8.6 ng/mL in the reference group (P < 0.001). Vitamin D deficiency and insufficiency were defined as 25(OH)D concentrations < 11 ng/mL and < 30 ng/mL, respectively. Seven percent of the CF group and 2% of the healthy reference group were vitamin D deficient (P < 0.03). Ninety percent of the CF group and 74% of the healthy reference group were vitamin D insufficient (P < 0.01). Twenty-five percent of the CF group and 9% of the healthy reference group had elevated PTH (P < 0.006). The odds of vitamin D insufficiency in the CF group, compared with the healthy reference group, were 1.2 (95% CI: 1.1, 1.3) after adjustment for season and age. CONCLUSION: Despite daily vitamin D supplementation, serum 25(OH)D concentrations remain low in children, adolescents, and young adults with CF.
Purpose
The aim of the study was to evaluate markers of oxidative stress and vitamin D receptor in paraspinal muscles in low back pain patients with vitamin D deficiency, with normal level of vitamin ...D, and after 5 weeks of vitamin D supplementation.
Methods
Patients were divided into three groups: supplemented (SUP) with vitamin D, placebo with normal concentration of vitamin D (SUF), and the placebo group with vitamin D deficiency (DEF). The concentration of serum vitamin D was measured before and after the supplementation with vitamin D (3200 IU/ day for 5 weeks). Markers of lipid and protein peroxidation, the activity of antioxidant enzymes, and protein content of vitamin D receptor was determined in multifidus muscle of patients.
Results
Vitamin D supplementation increased serum level of 25(OH)D
3
(
p
< 0.001). In paraspinal muscle level of 8-isoprostanes and protein carbonyls was higher in DEF group as compared to the SUP group (
p
< 0.05). Antioxidant enzyme activity and vitamin D receptor in paraspinal muscle altered between the groups with different serum vitamin D concentration. The cytosolic superoxide dismutase and glutathione peroxidase activities were significantly higher in DEF group as compared to the SUP group (
p
< 0.05).
Conclusions
An attenuation of markers of free radical damage of lipids and proteins was observed in participants supplemented with Vitamin D. Antioxidant enzyme activities in skeletal muscle differ among patients with different serum vitamin D concentration. Monitoring oxidative stress and VDR protein content might be useful for future studies on the mechanism(s) of vitamin D action in muscle.
Vitamin D plays a crucial role in many infectious diseases, such as tuberculosis (TB), that remains one of the world's top infectious killers with 1.5 million deaths from TB in 2021. Vitamin D ...suppresses the replication of
in vitro and showed a promising role in TB management as a result of its connection with oxidative balance. Our review encourages the possible in vivo benefit of a joint administration with other vitamins, such as vitamin A, which share a known antimycobacterial action with vitamin D. However, considering the low incidence of side effects even at high dosages and its low cost, it would be advisable to assess vitamin D level both in patients with active TB and high-risk groups and administer it, at least to reach sufficiency levels.
All vitamins play essential roles in various aspects of body function and systems. Patients with chronic kidney disease (CKD), including those receiving dialysis, may be at increased risk of ...developing vitamin deficiencies due to anorexia, poor dietary intake, protein energy wasting, restricted diet, dialysis loss, or inadequate sun exposure for vitamin D. However, clinical manifestations of most vitamin deficiencies are usually subtle or undetected in this population. Testing for circulating levels is not undertaken for most vitamins except folate, B12, and 25-hydroxyvitamin D because assays may not be available or may be costly to perform and do not always correlate with body stores. The last systematic review through 2016 was performed for the Kidney Disease Outcome Quality Initiative (KDOQI) 2020 Nutrition Guideline update, so this article summarizes the more recent evidence. We review the use of vitamins supplementation in the CKD population. To date there have been no randomized trials to support the benefits of any vitamin supplementation for kidney, cardiovascular, or patient-centered outcomes. The decision to supplement water-soluble vitamins should be individualized, taking account the patient’s dietary intake, nutritional status, risk of vitamins deficiency/insufficiency, CKD stage, comorbid status, and dialysis loss. Nutritional vitamin D deficiency should be corrected, but the supplementation dose and formulation need to be personalized, taking into consideration the degree of 25-hydroxyvitamin D deficiency, parathyroid hormone levels, CKD stage, and local formulation. Routine supplementation of vitamins A and E is not supported due to potential toxicity. Although more trial data are required to elucidate the roles of vitamin supplementation, all patients with CKD should undergo periodic assessment of dietary intake and aim to receive various vitamins through natural food sources and a healthy eating pattern that includes vitamin-dense foods.
Background
Metabolomic assessment of the transsulfuration and folic acid biochemical pathways could lead to the identification of promising biomarkers of nitric oxide dysregulation and oxidative ...stress in rheumatoid arthritis (RA).
Methods
We conducted a systematic review and meta‐analysis of transsulfuration (methionine, homocysteine, and cysteine) and folic acid (folic acid, vitamin B6, and vitamin B12) metabolites in RA patients in remission and healthy controls. Electronic databases were searched from inception to 15 July 2023 for relevant articles. We assessed the risk of bias using the JBI checklist and the certainty of evidence using GRADE.
Results
In 28 eligible studies, compared to controls, RA patients had significantly higher concentrations of homocysteine (standardized mean difference, SMD = 0.74, 95% CI 0.54–0.93, p < 0.001; low certainty of evidence) and methionine (SMD = 1.00, 95% CI 0.57–1.44, p < 0.001; low certainty) and lower concentrations of vitamin B6 (SMD = −6.62, 95% CI −9.65 to −3.60, p < 0.001; low certainty). By contrast, there were non‐significant between‐group differences in vitamin B12 and folic acid. In meta‐regression and subgroup analysis, there were no associations between the effect size and several study and patient characteristics except for homocysteine (year of publication, C‐reactive protein, triglycerides, and analytical method) and folic acid (biological matrix).
Conclusions
The results of our study suggest that homocysteine, methionine, and vitamin B6 are promising biomarkers to assess nitric oxide dysregulation and oxidative stress in RA. (PROSPERO registration number: CRD42023461081).
Our systematic review and meta‐analysis reported specific alterations in homocysteine, methionine, and vitamin B6, metabolites within the transsulfuration and folic acid pathways, in patients with RA in remission when compared to healthy controls. By contrast, there were no significant between‐group differences in folic acid or vitamin B12. Meta‐regression and subgroup analyses showed significant associations between the effect size of the between‐group differences in homocysteine (year of publication, CRP, triglycerides, and analytical method) and folic acid (biological matrix).
Vitamin D is a key component for optimal growth and for calcium–phosphate homeostasis. Skin photosynthesis is the main source of vitamin D. Limited sun exposure and insufficient dietary vitamin D ...supply justify vitamin D supplementation in certain age groups. In older adults, recommended doses for vitamin D supplementation vary between 200 and 2000 IU/day, to achieve a goal of circulating 25-hydroxyvitamin D (calcifediol) of at least 50 nmol/L. The target level depends on the population being supplemented, the assessed system, and the outcome. Several recent large randomized trials with oral vitamin D regimens varying between 2000 and 100,000 IU/month and mostly conducted in vitamin D-replete and healthy individuals have failed to detect any efficacy of these approaches for the prevention of fracture and falls. Considering the well-recognized major musculoskeletal disorders associated with severe vitamin D deficiency and taking into account a possible biphasic effects of vitamin D on fracture and fall risks, an European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group convened, carefully reviewed, and analyzed the meta-analyses of randomized controlled trials on the effects of vitamin D on fracture risk, falls or osteoarthritis, and came to the conclusion that 1000 IU daily should be recommended in patients at increased risk of vitamin D deficiency. The group also addressed the identification of patients possibly benefitting from a vitamin D loading dose to achieve early 25-hydroxyvitamin D therapeutic level or from calcifediol administration.
Depression is the most common debilitating psychiatric disease, the pathological mechanisms of which are associated with multiple aspects of neural function. While recent evidence has consistently ...suggested that a suboptimal vitamin D status is frequently observed in patients with depression, the results concerning whether vitamin D insufficiency is a causal factor of depression or is secondary to depressive behavior are conflicting; additionally, the lack of consistency of the method of vitamin D determination between labs has further worsened this confusion. Herein, we reviewed the neuroactivities of vitamin D that may be associated with depression and the current studies and clinical investigations to provide a full overview on the use of vitamin D in the treatment and prevention of depression.
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