Circulating Levels Of Vitamin Research Articles

A-340 CFTR Modulator Therapy Increases Serum/Plasma Concentrations of Vitamin a in People with Cystic Fibrosis

Abstract Introduction Pancreatic insufficiency (PI) is common in people with Cystic Fibrosis (PwCF), contributing to malabsorption of fat and fat-soluble vitamins. Thus, PI PwCF are prescribed pancreatic enzyme replacement therapy (PERT) and supplementation with fat-soluble vitamins. The circulating vitamin levels are monitored to guide dietary therapy. Currently, there are multiple cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies available that have shown significant improvements in pulmonary function, anthropometric parameters, and life expectancy in PwCF, but the effects on serum/plasma fat-soluble vitamin levels remain unknown. The goal of this study was to determine how modulator therapy affects serum/plasma vitamin A and E levels in individuals with CF. Methods The analysis included 1139 serum/plasma samples from 157 children and adolescents with CF: 74 males, 83 females, between the ages of 2–17 years. Most individuals were homozygous or compound heterozygous for the F508del variant (n = 81 and n = 72, respectively). 141 individuals (90%) were diagnosed with PI (fecal elastase <200 μg/g stool). 76 individuals (48%) received different CFTR modulator therapies for at least 1 month. Vitamin A (retinol and retinyl palmitate) and Vitamin E (α-tocopherol and γ-tocopherol) were measured using a high-performance liquid chromatography assay. Data analyses were performed in Prism software (La Jolla, CA), and statistical significance was defined as P < 0.05. The study was approved by the IRB. Results Overall, vitamin deficiency was rarely observed in PwCF prescribed PERT and vitamin supplements; <3% of them had low concentrations of Vitamin A and/or E. The proportion of individuals with Vitamin A and/or E above the reference range was larger; 10.9% and 30.8% for Vitamin A and E, respectively, most likely reflecting supplementation. There was no correlation of plasma vitamin A or E results with sex, weight-for-age, height-for-age, or BMI-for-age. However, pancreatic status affected vitamin levels in individuals not taking modulators: samples from PI PwCF (n = 367) had significantly lower Vitamin A and E than those from PS PwCF (n = 71). In contrast, we have observed higher concentrations of Vitamin A retinol in individuals on modulators: 0.49 ± 0.13 mg/L on modulators vs 0.43 ± 0.12 mg/L without modulators. Pairwise analysis of samples from 76 individuals before and after modulator therapy confirmed this finding, showing an average 16% increase in serum/plasma retinol concentration (P < 0.0001). No changes in retinol were observed between different measurements in PwCF who were not taking modulators (n = 82). Vitamin E levels were not impacted by modulator therapy. Conclusions Advances in clinical care improved fat-soluble vitamin status in people with CF. However, even when supplemented and on PERT, PI PwCF not on modulators tend to have lower fat-soluble vitamin concentrations than PS PwCF. CFTR modulator therapy increases serum/plasma concentrations of vitamin A. Thus, individuals receiving modulators and vitamin supplementation should be monitored to avoid Vitamin A toxicity. This is especially true for PS PwCF who already have higher baseline vitamin levels.

Circulating vitamin levels mediate the causal relationship between gut microbiota and cholecystitis: a two-step bidirectional Mendelian randomization study.

The relationship between gut microbiota and the occurrence of cholecystitis remains unclear. Existing research lacks a clear understanding of how circulating vitamin levels modulate this relationship. Therefore, our study aims to investigate whether circulating vitamin levels mediate the causal relationship between gut microbiota and cholecystitis using a two-step bidirectional Mendelian randomization approach. In this study, we initially employed Linkage Disequilibrium Score Regression (LDSC) analysis to assess the genetic correlation of five circulating vitamin level genome-wide association study (GWAS) summary datasets, thereby avoiding potential sample overlap. Subsequently, we conducted a two-step analysis to investigate the causal effects between gut microbiota and cholecystitis. In the second step, we explored the causal relationship between circulating vitamin levels and cholecystitis and identified the mediating role of vitamin D. The primary method used for causal analysis was the inverse variance-weighted approach. We performed additional sensitivity analyses to ensure result robustness, including the cML-MA method and reverse Mendelian randomization (MR) analysis. An increment of one standard deviation in RuminococcaceaeUCG003 was associated with a 25% increased risk of cholecystitis (OR = 1.25, 95%CI = 1.01-1.54, p = 0.04), along with a 3% decrease in 25-hydroxyvitamin D levels (OR = 0.97, 95%CI = 0.944-0.998, p = 0.04). However, following the rigorous Bonferroni correction, every one standard deviation decrease in circulating vitamin D levels was associated with a 33% increased risk of cholecystitis (OR = 0.67, 95%CI = 0.49-0.90, p = 0.008, Padjust = 0.04). Thus, the potential link between gut microbiota and cholecystitis risk might be mediated by circulating vitamin D levels (proportion mediated = 5.5%). Sensitivity analyses provided no evidence of pleiotropy. Our study results suggest that an elevated abundance of specific gut microbiota is associated with an increased susceptibility to cholecystitis, with the causal relationship being mediated by circulating vitamin D levels. Further large-scale randomized controlled trials are necessary to validate the causal effects of gut microbiota on cholecystitis risk. This study provides novel insights into cholecystitis prevention through the regulation of gut microbiota.

Causal effects of circulating vitamin levels on the risk of heart failure: a Mendelian randomization study.

Observational studies suggest inverse associations between serum vitamin levels and the risk of heart failure (HF). However, the causal effects of vitamins on HF have not been fully elucidated. Here, we conducted a Mendelian randomization (MR) study to investigate the causal associations between genetically determined vitamin levels and HF. Genetic instrumental variables for circulating vitamin levels, including vitamins A, B, C, D, and E, which were assessed as either absolute or metabolite levels were obtained from public genome-wide association studies. Summary statistics for single-nucleotide-polymorphisms and HF associations were retrieved from the HERMES Consortium (47,309 cases and 930,014 controls) and FinnGen Study (30,098 cases and 229,612 controls). Two-sample MR analyses were implemented to assess the causality between vitamin levels and HF per outcome database, and the results were subsequently combined by meta-analysis. Our MR study did not find significant associations between genetically determined circulating vitamin levels and HF risk. For absolute vitamin levels, the odds ratio for HF ranged from 0.97 (95% confidence interval [CI]: 0.85-1.09, P = 0.41) for vitamin C to 1.05 (95% CI: 0.61-1.82, P = 0.85) for vitamin A. For vitamin metabolites, the odds ratio ranged between 0.94 (95% CI: 0.75-1.19, P = 0.62) for α-tocopherol and 1.11 (95% CI: 0.98-1.26, P = 0.09) for γ-tocopherol. Evidence from our study does not support the causal effects of circulating vitamin levels on HF. Therefore, there may be no direct beneficial effects of vitamin intake on the prevention of primary HF.

Vitamin D in obesity and obesity-related diseases: an overview

Hypovitaminosis D and obesity represent two pandemic conditions sometimes associated with each other. Although it is known that there is a close relationship between these two health problems, the underlying pathophysiological mechanism has not yet been fully clarified. In fact, on the one hand, obesity per se seems to involve low circulating levels of vitamin D due to low sun exposure, physical activity, and intake of foods rich in vitamin D, volumetric dilution and sequestration in the adipose tissue. Conversely, since preadipocytes and adipocytes express the receptors and are involved in the metabolism of vitamin D it would seem that low levels of this vitamin may be involved in adipogenesis and therefore in the development of obesity. This connection is extremely important when considering obesity-related diseases. In fact, low vitamin D levels and severe obesity are significantly associated with some cardio-metabolic risk factors, including high Body Mass Index, waist circumference, blood pressure, impaired lipid and glycemic profile and insulin resistance, as they would seem associated with worse cardiovascular outcomes and higher cancer incidence and mortality. Therefore, the purpose of this review was to examine the recent evidence linking low vitamin D status, obesity and obesity-related diseases, highlighting the scientific achievements and the gaps to be filled with further investigations.

Вітамін D у генетичному аспекті та його роль за цукрового діабету 1-го типу

Вітамін D бере участь у різноманітних біологічних процесах, включаючи кістковий метаболізм, модуляцію імунної відповіді та регуляцію проліферації й диференціювання клітин. Дефіцит вітаміну D пов’язують із впливом на виникненням таких нескелетних захворювань, як цукровий діабет 1-го та 2-го типів, рак, серцево-судинні захворювання, що підтверджує плейотропний характер біологічної дії вітаміну D. Генетичні дослідження дають можливість вивчити генетично-молекулярні механізми впливу на циркулюючі рівні вітаміну D. Варіативні ділянки ДНК, які часто трапляються в популяції — однонуклеотидні поліморфізми (OHП, SNP) — можуть справляти вплив на метаболізм вітаміну D, а також модулювати дію вітаміну D у ході розвитку цукрового діабету 1-го типу. В огляді описано дані літератури щодо молекулярних механізмів дії вітаміну D, а також генів, які кодують ензими, відповідальні за його метаболізм, розглянуто генетичні дослідження різного типу в людських популяціях, метою яких було вивчення успадкування циркулюючих рівнів вітаміну D, вплив цих генетичних детермінант на розвиток цукрового діабету 1-го типу.

Explore new approaches to prevent and treat type 2 diabetes with vitamin D and its active analogues——From somewhat disappointing clinical trials results to promising basic researches

The prevalence of diabetes is increasing rapidly which becomes a serious economic burden to society. The effects of vitamin D beyond bone are increasingly recognized. Circulating level of vitamin D is associated with the development of obesity and type 2 diabetes in cross-sectional human studies. However, as to the therapeutic efficacy of vitamin D supplementation on the prevention of diabetes, the results derived from randomized controlled clinical trials were disappointing, probably due to variations in the vitamin D receptor genotypes, the dosages and courses of vitamin D treatments. However, two recent basic studies found that central administration of active vitamin D can improve glucose metabolism in diet induced obesity rats; and the combining use of active vitamin D analogue and BRD9 inhibitor rendered the chromatin of vitamin D response elements more accessible, thus more efficiently exerted its anti-inflammatory efficacy and protected islet β cell function in obese and diabetic mice models. Thus it is paramount important to explore some new approaches to prevent and treat diabetes with vitamin D and its active analogues. (Chin J Endocrinol Metab, 2018, 34: 992-996) Key words: Vitamin D; Vitamin D receptor; Diabetes mellitus, type 2

Vitamin D: It's not just for bones anymore

It has become apparent that large segments of the population have vitamin D deficiency or insufficiency. This is of concern because vitamin D has biologic actions that influe nce immunity, inflammation, and oncogenesis in more than 30 tissues types with vitamin D receptors. Vitamin D deficiency has been associated with numerous disorders, including diabetes, rheumatoid arthritis, multiple sclerosis, and several typ es of cancer. Sufficient circulating levels of vitamin D are c ritical not only for healthy bones, but for many aspects of human health. The maintenance of adequate body stores of vitamin D depends on exposure to sunlight and dietary intake. Cutaneous synthesis of vitamin D and safe levels of dietary supplementation are discussed.

Long-term vitamin C treatment increases vascular tetrahydrobiopterin levels and nitric oxide synthase activity.

In cultured endothelial cells, the antioxidant, L-ascorbic acid (vitamin C), increases nitric oxide synthase (NOS) enzyme activity via chemical stabilization of tetrahydrobiopterin. Our objective was to determine the effect of vitamin C on NOS function and tetrahydrobiopterin metabolism in vivo. Twenty-six to twenty-eight weeks of diet supplementation with vitamin C (1%/kg chow) significantly increased circulating levels of vitamin C in wild-type (C57BL/6J) and apolipoprotein E (apoE)--deficient mice. Measurements of NOS enzymatic activity in aortas of apoE-deficient mice indicated a significant increase in total NOS activity. However, this increase was mainly due to high activity of inducible NOS, whereas eNOS activity was reduced. Significantly higher tetrahydrobiopterin levels were detected in aortas of apoE-deficient mice. Long-term treatment with vitamin C restored endothelial NOS activity in aortas of apoE-deficient mice, but did not affect activity of inducible NOS. In addition, 7,8-dihydrobiopterin levels, an oxidized form of tetrahydrobiopterin, were decreased and vascular endothelial function of aortas was significantly improved in apoE-deficient mice. Interestingly, vitamin C also increased tetrahydrobiopterin and NOS activity in aortas of C57BL/6J mice. In contrast, long-term treatment with vitamin E (2000 U/kg chow) did not affect vascular NOS activity or metabolism of tetrahydrobiopterin. In vivo, beneficial effect of vitamin C on vascular endothelial function appears to be mediated in part by protection of tetrahydrobiopterin and restoration of eNOS enzymatic activity.

Vitamin A and E Supplementation in Breast‐Fed Newborns

ABSTRACTBackgroundVitamins A and E are two potent antioxidant nutrients that play a significant role in immune function. In contrast to the numerous studies of vitamin A and E status in children, adolescents, and adults, information on term infants, particularly breast‐fed infants, is scarce. The goals of the present investigation were to examine the vitamins A and E nutritional status of term breast‐fed infants at birth and to assess retinol and tocopherol plasma levels during a 3‐month supplementation trial.MethodsThe study was a prospective, blinded comparison of a supplementation protocol with a placebo in a group of consecutively recruited term newborns. The supplemented group received 3000 IU vitamin A and 5 IU vitamin E orally. The placebo group received a solution of similar viscosity and organoleptic characteristics. Vitamin A and E were separated by reverse‐phase high‐performance liquid chromatography on a C18 Spectrasyl column and quantified by ultraviolet spectrophotometry.ResultsVitamin A and E levels steadily increased with age in both groups of infants. However, levels at 3 months were higher in the supplemented than in the control group.ConclusionThe data show that supplementation with 3000 IU vitamin A and 5 IU vitamin E for 3 months increases circulating vitamin levels in newborn term babies compared with those in nonsupplemented infants.

Dietary intake and circulating vitamin levels of rheumatoid arthritis patients treated with methotrexate

The nutrient intakes and circulating vitamin levels of 32 patients with rheumatoid arthritis who were treated with methotrexate were evaluated over a 6-month period. Dietary data were obtained and blood was drawn prior to the initiation of and following 12 and 24 weeks of methotrexate therapy. More than 50% of the patients had food intakes providing less than 67% of the recommended dietary allowance for zinc, vitamin E, folic acid, pyridoxine, and magnesium. Patients 51 years or older had better nutrient intakes than patients less than 51 years. Of the patients, 22% consumed vitamin supplements at the time they were recruited for the study. Mean circulating vitamin levels measured over the 6-month period were within normal limits. Our findings agree with previously published reports that patients with rheumatoid arthritis, particularly the subpopulation taking methotrexate, consume diets that are marginal in some nutrients. Additional research needs to be done to identify more sensitive nutrient assays and to establish more definitively the nutrient needs of patients with rheumatoid arthritis taking several therapeutic agents.

Vitamin profile of 174 mothers and newborns at parturition

Thiamin, biotin, B12, folate, pantothenate, riboflavin, nicotinate, B6, vitamins A, E, C, and beta-cartene was estimated in the blood of 174 mothers and in the cord blood of their neonates at parturition. A vitamin profile of normal preganancy was established for mother and neonate. This was based on values obtained from 95 percent confidence limits in 74 mothers not taking oral vitamins and 133 mothers ingesting various vitamin supllements. Circulating vitamin levels in 38 neonates born to mothers with no laboratory evidence of hypovitaminemia was persented. The higher incidence of hypobitaminemia in gravidas not taking vitamins was folate, thiamin, vitamins A, C, B12, BL and nicotinate in descending order. Ingestion of vitamins supplements reduced the incidence of hypovitaminemia. A similar relationship held for neonates from these mothers. However, despite vitamin ingestion thiamin, folate, vitamins C, A, B6, B12 and nicotinate hypovitaminemia was evident. There was an approximate 1:2-5 ratio between mother and neonate blood vitamins; vitamins A, B6, E, and beta-carotene were exceptions. Vitamin B6 ran parallel, while vitamins A, B6, E, and beta-carotene ratios reversed in favor of the mother at an approximate ratio of 2:1, 4:1 and 7:1, respectively. It is concluded that vitamin profile for mother and neonate, taking into account values established from a lorge gravid population, should now permit an evaluation of the effects of hypoviteminemia on the outcome of pregnancy and infant health.