ascorbic-acid and Inflammatory-Bowel-Diseases

Recent research studies have shown that vitamin C (ascorbic acid) may affect bone mineral density and that a deficiency of ascorbic acid leads to the development of osteoporosis. Patients suffering from an inflammatory bowel disease are at a risk of low bone mineral density. It is vital to notice that patients with Crohn's disease and ulcerative colitis also are at risk of vitamin C deficiency which is due to factors such as reduced consumption of fresh vegetables and fruits, i.e., the main sources of ascorbic acid. Additionally, some patients follow diets which may provide an insufficient amount of vitamin C. Moreover, serum vitamin C level also is dependent on genetic factors, such as

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Bone Density; Colitis, Ulcerative; Crohn Disease; Diet; Female; Gastrointestinal Microbiome; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Inflammatory Bowel Diseases; Male; Osteoporosis; Risk Factors; Sodium-Coupled Vitamin C Transporters

We evaluated the efficacy, safety and tolerability of novel oral sulphate tablets [OSTs] vs 2 L of polyethylene glycol and ascorbate [PEG/Asc] in patients with inflammatory bowel disease [IBD].. A total of 110 patients with clinically inactive IBD were enrolled in this single-blind multicentre non-inferiority study. Patients were randomly assigned to the OST or 2 L PEG/Asc group and we applied a split-dose regimen. The primary efficacy endpoint was bowel cleansing success rate defined as Harefield Cleansing Scale Grade A or B. The secondary endpoints were perfect preparation rate, the presence of air bubbles, safety as assessed by laboratory abnormalities and self-reported adverse events, or IBD symptom flare-ups. Tolerability was assessed by a pre-procedural visual analog scale [VAS] interview.. Both groups showed high cleansing success rates [98.1%] and there was no significant difference in perfect preparation rate. The proportion of a bubble score 0 was significantly higher in the OST group [94.5% vs 50.0%, p < 0.001]. There was no significant intergroup difference in vomiting or bloating. Symptom flare-ups occurred in two OST group patients. No clinically significant blood test abnormalities were noted in either group. Ease of ingestion and taste scores were significantly higher in the OST group. More patients in the OST group [94.5%] wanted to take the same preparation agent for their next colonoscopy.. Both OST and 2 L PEG/Asc demonstrated high successful cleansing and safety in patients with inactive IBD. OST achieved higher satisfaction than 2 L PEG/Asc. Our results suggest that the OST split-dose regimen is effective and safe for patients with inactive IBD.

Topics: Ascorbic Acid; Cathartics; Colonoscopy; Humans; Inflammatory Bowel Diseases; Polyethylene Glycols; Single-Blind Method; Sulfates; Symptom Flare Up; Tablets

Reactive oxygen species (ROS), which are exceptionally high in IBD lesions, are known to cause abnormal immune responses to inflammatory reactions in inflammatory bowel diseases (IBD) through damage to the intestinal mucosal linings. Moreover, they are theorized to be an agent of IBD development. Vitamin C is widely known to be an effective antioxidant for its ability to regulate inflammatory responses through its ROS scavenging effect. Therefore, we examined vitamin C's influence on the development and progression of IBD in Gulo(-/-) mice, which cannot synthesize vitamin C like humans due to a defect in the expression of L-gulono-γ-lactone oxidase, an essential enzyme for vitamin C production. First, we found extensive oxidative stress and an inflammation increase in the colon of vitamin C-insufficient Gulo(-/-) mice. We also found decreased IL-22 production and NKp46(+) cell recruitment and the impaired activation of the p38MAPK pathway. Additionally, comparing vitamin C-insufficient Gulo(-/-) mice to vitamin C-sufficient Gulo(-/-) mice and wild-type mice, the insufficient group faced a decrease in mucin-1 expression, accompanied by an increase in IL-6 production, followed by the activation of the STAT3 and Akt pathways. The results suggest that vitamin C insufficiency induces severe colitis, meaning vitamin C could also take on a preventative role by regulating the production of cytokines and the induction of inflammation.

Topics: Animals; Antioxidants; Ascorbic Acid; Colitis; Cytokines; Dextran Sulfate; Humans; Inflammation; Inflammatory Bowel Diseases; Interleukin-22; Interleukin-6; Interleukins; L-Gulonolactone Oxidase; Mice; Mice, Inbred C57BL; Mucin-1; Mustelidae; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Vitamins

Patients with inflammatory bowel disease (IBD) are prone to several nutritional deficiencies. However, data are lacking on vitamin C deficiency in Crohn's disease (CD) and ulcerative colitis (UC) patients, as well as the impact of clinical, biomarker and endoscopic disease severity on the development of vitamin C deficiency.. To determine proportions and factors associated with vitamin C deficiency in CD and UC patients.. In this retrospective study, we obtained clinical, laboratory and endoscopic data from CD and UC patients presenting to the IBD clinic at a single tertiary care center from 2014 to 2019. All patients had an available plasma vitamin C level. Of 353 subjects who met initial search criteria using a cohort discovery tool, 301 ultimately met criteria for inclusion in the study. The primary aim described vitamin C deficiency (≤ 11.4 μmol/L) rates in IBD. Secondary analyses compared proportions with deficiency between active and inactive IBD. Multivariate logistic regression analysis evaluated factors associated with deficiency.. Of 301 IBD patients, 21.6% had deficiency, including 24.4% of CD patients and 16.0% of UC patients. Patients with elevated C-reactive protein (CRP) (39.1%. Vitamin C deficiency was common in IBD. Patients with elevated inflammatory markers and penetrating disease had higher rates of vitamin C deficiency.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Biological Products; Biomarkers; C-Reactive Protein; Chronic Disease; Colitis, Ulcerative; Crohn Disease; Humans; Inflammatory Bowel Diseases; Leukocyte L1 Antigen Complex; Prevalence; Retrospective Studies; Scurvy; Vitamin D Deficiency

Current efforts on inflammatory bowel diseases (IBD) treatment are focused on strategies for localised drug delivery at the intestinal mucosa. Despite the potential of curcumin (CC) for IBD treatment, its low solubility and stability limit its application. Thus, the design of nanocarriers that focus CC delivery at the intestinal epithelium is an area of interest. This work proposes α-tocopherol nanoemulsions (NE) stabilised by ascorbyl-2,6-dipalmitate (ADP) as intestinal CC-carriers. The antioxidant capacity of α-tocopherol and ADP could have a synergistic effect on IBD-affected tissues, characterised by an oxidative environment. We obtained nanoemulsions (NE-ADP) with size below 200 nm, negative surface charge, stable in gastrointestinal media and no toxic in the Caco-2 cell model. Intracellular retention of NE-ADP in Caco-2 cells was observed by confocal microscopy. The extremely low P

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; Biological Transport; Caco-2 Cells; Curcumin; Drug Carriers; Drug Delivery Systems; Emulsions; Humans; Inflammatory Bowel Diseases; Lecithins; Nanoparticles; Palmitates; Particle Size; Reactive Oxygen Species; Solubility

Sodium-dependent vitamin C transporter-1 (SVCT-1) is the major transporter mediating intestinal vitamin C uptake. Intestinal inflammation and prolonged infection are associated with increased serum and intestinal mucosa levels of tumor necrosis factor-α (TNF-α), which also exerts profound effects on the intestinal absorption process. Elevated levels of TNF-α have been linked to the pathogenesis of inflammatory bowel disease (IBD) and malabsorption of nutrients, and patients with this condition have low levels of vitamin C. To date, little is known about the effect of TNF-α on intestinal absorption of vitamin C. We studied the impact of TNF-α on ascorbic acid (AA) transport using a variety of intestinal preparations. The expression level of human SVCT-1 mRNA is significantly lower in patients with IBD. TNF-α treated Caco-2 cells and mice showed a significant inhibition of intestinal

Topics: Animals; Ascorbic Acid; Biological Transport; Caco-2 Cells; Humans; Inflammatory Bowel Diseases; Intestinal Absorption; Intestinal Mucosa; Mice; NF-kappa B; Sodium-Coupled Vitamin C Transporters; Tumor Necrosis Factor-alpha; Vitamins

Topics: Ascorbic Acid; Gastrointestinal Microbiome; Humans; Inflammatory Bowel Diseases; T-Lymphocytes; Vitamins

A characteristic feature of malignant cells, such as colorectal cancer cells, is a profound decrease in the level of 5-hydroxymethylcytosine, a product of 5-methylcytosine oxidation by TET enzymes. Recent studies showed that ascorbate may upregulate the activity of TET enzymes in cultured cells and enhance formation of their products in genomic DNA.. The study included four groups of subjects: healthy controls (n = 79), patients with inflammatory bowel disease (IBD, n = 51), adenomatous polyps (n = 67) and colorectal cancer (n = 136). The list of analyzed parameters included (i) leukocyte levels of epigenetic DNA modifications and 8-oxo-7,8-dihydro-2'-deoxyguanosine, a marker of oxidatively modified DNA, determined by means of isotope-dilution automated online two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry, (ii) expression of TET mRNA measured with RT-qPCR, and (iii) chromatographically-determined plasma concentrations of retinol, alpha-tocopherol and ascorbate.. Patients from all groups presented with significantly lower levels of 5-methylcytosine and 5-hydroxymethylcytosine in DNA than the controls. A similar tendency was also observed for 5-hydroxymethyluracil level. Patients with IBD showed the highest levels of 5-formylcytosine and 8-oxo-7,8-dihydro-2'-deoxyguanosine of all study subjects, and individuals with colorectal cancer presented with the lowest concentrations of ascorbate and retinol. A positive correlation was observed between plasma concentration of ascorbate and levels of two epigenetic modifications, 5-hydroxymethylcytosine and 5-hydroxymethyluracil in leukocyte DNA. Moreover, a significant difference was found in the levels of these modifications in patients whose plasma concentrations of ascorbate were below the lower and above the upper quartile for the control group.. These findings suggest that deficiency of ascorbate in the blood may be a marker of its shortage in other tissues, which in turn may correspond to deterioration of DNA methylation-demethylation. These observations may provide a rationale for further research on blood biomarkers of colorectal cancer development.

Topics: Adenoma; Aged; alpha-Tocopherol; Ascorbic Acid; Case-Control Studies; Colorectal Neoplasms; DNA; Epigenesis, Genetic; Female; Humans; Inflammatory Bowel Diseases; Leukocytes; Male; Proto-Oncogene Proteins; RNA, Messenger; Vitamin A

Topics: Alcoholic Intoxication; Ascorbic Acid; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Purpura; Scurvy; Vasculitis

Data regarding the nutritional status, antioxidant compounds and plasma fatty acid (FA) composition in inactive IBD are conflicting. We compared plasma levels of antioxidants and FA of patients with inactive IBD with active IBD and controls.. Plasma levels of vitamin C, vitamin E, carotenoids, saturated, monounsaturated and polyunsaturated FA, inflammatory markers and nutritional status were determined after an overnight fast in 132 patients with quiescent IBD (40.6+/-13.2 years, 87F/45M), 35 patients with active disease (37.9+/-12.1 years, 25F/10M) and 45 age- and BMI-matched healthy controls (38.1+/-10.5 years, 39F/6M). Results are expressed as mean+/-SD or median [25th percentile;75th percentile].. Body mass index (BMI) was normal in inactive (23.9+/-4.7 kg/m(2)), active IBD (22.7+/-4.2 kg/m(2)) and controls (22.3+/-1.9 kg/m(2)). Compared with controls patients with quiescent IBD showed significantly decreased plasma levels of carotenoids (1.85 [1.37;2.56] vs 1.39 [0.88;1.87] micromol/L) and vitamin C (62.3 [48.7;75.0] vs 51.0 [36.4;77.6] micromol/L), increased levels of saturated FA (3879 [3380;4420] vs 3410 [3142;3989] micromol/L) and monounsaturated FA (2578 [2258;3089] vs 2044 [1836;2434] micromol/L) and similar levels of vitamin E and polyunsaturated FA. Results in active disease were similar to inactive disease.. This study shows that antioxidant status and FA profile in a larger population of IBD patients are disturbed independently from disease activity and despite normal overall nutritional status.

Topics: Adult; Antioxidants; Ascorbic Acid; Body Mass Index; C-Reactive Protein; Carotenoids; Case-Control Studies; Fatty Acids; Fatty Acids, Unsaturated; Female; Humans; Inflammation; Inflammatory Bowel Diseases; Male; Nutritional Status; Oxidation-Reduction; Surveys and Questionnaires; Vitamin E; Vitamins

Topics: Ascorbic Acid; Child; Humans; Inflammatory Bowel Diseases

The mechanisms by which inflammatory bowel disease causes chronic injury to the gastrointestinal tract are poorly understood. To determine whether antioxidant defenses might be altered, we evaluated plasma antioxidant concentrations in 24 children with inflammatory bowel disease (12 with Crohn disease and 12 with ulcerative colitis) and in 23 healthy control subjects. Anthropometric measurements and disease activity scores were obtained. The groups were of similar age and sex distribution; most children had quiescent or mild disease. The children with Crohn disease were malnourished compared with the ulcerative colitis and control groups. Children with inflammatory bowel disease had decreased plasma ascorbic acid and increased glutathione peroxidase, glutathione, and alpha-tocopherol (vitamin E) concentrations compared with control subjects. These differences were found primarily in the children with Crohn disease. This study provides evidence that children with Crohn disease have alterations in circulating antioxidant defenses, possibly related to an ongoing oxidant stress.

Topics: Adolescent; Antioxidants; Ascorbic Acid; Child; Colitis, Ulcerative; Crohn Disease; Glutathione; Glutathione Peroxidase; Humans; Inflammatory Bowel Diseases; Vitamin E

Attempts to establish the presence of oxidant stress and tissue damage in inflammatory bowel disease (IBD) have relied on determining the capacity of peripheral blood inflammatory cells to produce reactive oxygen species (ROS) and other indirect indices. These approaches have failed to address whether or not there are adequate chemical antioxidant defences to prevent oxidative injury in the inflamed mucosa. In this investigation we have determined the mucosal concentrations of reduced and total ascorbic acid and the redox status in paired non-inflamed and inflamed mucosa using colonic biopsies from IBD patients. In inflamed mucosa from Crohn's disease (CD) patients, reduced and total ascorbic acid content decreased by 35% (p = 0.014 and p = 0.009, respectively). In ulcerative colitis (UC) patients, mucosal total ascorbic acid content decreased by 73% (p = 0.069) and reduced ascorbic acid by 41% (p = 0.014). The proportion of total ascorbic acid present in its reduced form in histologically normal mucosa from CD patients was unusually low at approximately 30%. In the paired-inflamed mucosa from CD patients, the redox ratio was also approximately 30% despite the loss of 35% of total ascorbate. In UC patients, the ascorbate redox ratio in the non-inflamed mucosa was 23% which increased to 51% in paired inflamed mucosa. This increase reflected the loss (73%) of total ascorbate. Reduction of dehydroascorbic acid by GSH/NADPH dependent dehydroascorbic acid reductase decreased significantly (p = 0.046) in inflamed mucosa from UC patients, suggesting that the capacity of the inflamed mucosa to maintain the concentration of reduced ascorbic acid is also diminished. HPLC analysis of mucosal preparations for diketogulonic acid, the decomposition product of dehydroascorbic acid, did not account for the loss of total ascorbate in the inflamed mucosa suggesting that ascorbate equivalents underwent further decomposition reactions or were excreted to the colonic lumen. We conclude that the normal luminal environment is strongly oxidising in character and that oxidant stress derived from inflammatory cells contributes to the loss of 35-73% total and reduced ascorbate. In absolute terms, the overall loss of this antioxidant buffering capacity would decrease the capacity of the inflamed mucosa to prevent oxidative tissue damage and hinder recovery of the inflamed mucosa.

Topics: 2,3-Diketogulonic Acid; Ascorbic Acid; Chromatography, High Pressure Liquid; Colitis, Ulcerative; Crohn Disease; Female; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Male; Oxidation-Reduction; Oxidoreductases

Be it ever so complex the natural antioxidant scavenger system of the organism, the protection provided by it seems to be inappropriate in certain diseases of the gastrointestinal mucus membrane, such as chronic inflammation, immune- and malignant diseases of the bowel. Despite the wide range of therapeutic attempts, the treatment of these diseases has not yet been solved, and the anti-inflammatory-, immunomodulatory-, cytostatic drugs currently used, have several side effects. Therefore, the so called natural- and synthetic antioxidants have been more widely employed for additional and adjuvant treatment. It also has become clear that the direct free radical scavenging effect and/or the membrane protection play an important role in the action mechanism of several old-established drugs. The recent report lists those natural and synthetic antioxidants which have been successfully employed in the clinical treatment of bowel diseases. Among the natural antioxidants, a protective effect of vitamins A, C and E have been demonstrated in the treatment of gastroduodenal ulcer and gastric cancer. Among the synthetic antioxidants, 5-amino-salicylic acid was the most effective drug in the treatment of chronic inflammations of the bowel. With getting the more precise knowledge about details of free radical reactions and with clearing up their role in pathological processes, it is possible to develop new and effective synthetic antioxidants, and widely employ them therapeutically.

Topics: Aminosalicylic Acids; Antioxidants; Ascorbic Acid; Free Radical Scavengers; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Humans; Inflammatory Bowel Diseases; Mesalamine; Mucous Membrane; Vitamin A; Vitamin E