ascorbic-acid and Gout

Gout, known as "the disease of the kings", is the most frequent type of arthritis. It results from sustained hyperuricemia that leads to monosodium urate crystal deposition in joint structures and soft tissue. Environmental factors such as diet affect the incidence of gout; there is a known relationship between the occurrence of an acute attack of gout and the consumption of alcohol and meat; and a low purine diet is a widely recognized nonpharmacological method of supplementing the treatment and preventing recurrence of arthritis. This review aims to summarize the current knowledge about the role of vitamin C in prevention and treatment of gout. A PubMed/Medline database search on the role of vitamin C in purine metabolism was done. Reports from in vitro and animal studies seem to be promising and to allow explanation of the physiological relationship between vitamin C and uric acid. Most epidemiological studies indicate a significant correlation between high vitamin C intake and lower serum uric acid levels. Despite promising observations, there are few observational and interventional studies, and their results do not clearly define the benefits of a high daily intake of vitamin C in preventing the development and recurrence of gout.

Topics: Ascorbic Acid; Diet; Gout; Humans; Hyperuricemia

The consumption of fructose has gained increased attention as a potential cause of hyperuricaemia since fructose metabolism produces urate as a byproduct. In addition to sucrose and high fructose corn syrup, fresh fruits also contain fructose, suggesting that patients with hyperuricaemia or gout might also avoid fresh fruit. However, the effect of fruits is complex. Some studies reported that fruit intake was associated with gout flares while other studies showed that fruits rather lowered the risk for gout. Thus, fruits should not be simply viewed as a source of fructose. The complexity of fruits is accounted for by several nutrients existing in fruits. Vitamin C, epicatechin, flavonols, potassium and fibre are all nutrients in fruits, and these factors could modify fructose and urate effects. In this review, we discuss clinical studies evaluating the effect of fruit and fruit juice intake on hyperuricaemia and gout, and propose potential mechanisms for how fruit may influence urate levels.

Topics: Ascorbic Acid; Dietary Fiber; Fructose; Fruit; Fruit and Vegetable Juices; Gout; Humans; Hyperuricemia; Prunus avium; Uric Acid

Gout is an inflammatory arthritis caused by deposition of monosodium urate crystals within synovial joints. Although it is most well-known for its arthritis, gout has an intimate relationship with many other cardiovascular and metabolic conditions. Current recommendations support aggressive medical therapy to treat gout, whereas dietary counseling has become less emphasized. This article argues for the absolute importance of dietary counseling in gout and proves why this counseling may impact the long term well-being of a patient with gout.

Topics: Alcohol Drinking; Ascorbic Acid; Carbonated Beverages; Coffee; Dairy Products; Diet Therapy; Disease Progression; Gout; High Fructose Corn Syrup; Humans; Hyperuricemia; Metabolic Syndrome; Purines; Tea; Vitamins

About 2500 years ago, gout was observed by Hippocrates and many people suffered severe pain and deformity. Lifestyle and diet play a significant role in gout and serum uric acid levels. Epidemiological and research studies have supported this evidence. Many recommendations and guidelines from different parts of the world mention the impact of diet on gout. Recently, new research has shown associations between vitamin C, alcohol, coffee, tea, milk and yogurt with uric acid and the risk of gout. Our review summarizes recently published research regarding dietary impact on the risk of gout and serum uric acid levels.

Topics: Animals; Ascorbic Acid; Coffee; Culture; Diet; Ethanol; Feeding Behavior; Female; Global Health; Gout; Humans; Life Style; Male; Milk; Risk Factors; Sex Factors; Tea; Uric Acid; Yogurt

Dietary supplements are frequently used for the treatment of several medical conditions, both prescribed by physicians or self administered. However, evidence of benefit and safety of these supplements is usually limited or absent.. To assess the efficacy and safety of dietary supplementation for people with chronic gout.. We performed a search in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL on 6 June 2013. We applied no date or language restrictions. In addition, we performed a handsearch of the abstracts from the 2010 to 2013 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) conferences, checked the references of all included studies and trial registries.. We considered all published randomised controlled trials (RCTs) or quasi-RCTs that compared dietary supplements with no supplements, placebo, another supplement or pharmacological agents for adults with chronic gout for inclusion. Dietary supplements included, but were not limited to, amino acids, antioxidants, essential minerals, polyunsaturated fatty acids, prebiotic agents, probiotic agents and vitamins. The main outcomes were reduction in frequency of gouty attacks and trial participant withdrawal due to adverse events. We also considered pain reduction, health-related quality of life, serum uric acid (sUA) normalisation, function (i.e. activity limitation), tophus regression and the rate of serious adverse events.. We used standard methodological procedures expected by The Cochrane Collaboration.. We identified two RCTs (160 participants) that fulfilled our inclusion criteria. As these two trials evaluated different diet supplements (enriched skim milk powder (SMP) and vitamin C) with different outcomes (gout flare prevention for enriched SMP and sUA reduction for vitamin C), we reported the results separately.One trial including 120 participants, at moderate risk of bias, compared SMP enriched with glycomacropeptides (GMP) with unenriched SMP and with lactose over three months. Participants were predominantly men aged in their 50's who had severe gout. The frequency of acute gout attacks, measured as the number of flares per month, decreased in all three groups over the study period.The effects of enriched SMP (SMP/GMP/G600) compared with the combined control groups (SMP and lactose powder) at three months in terms of mean number of gout flares per month were uncertain (mean ± standard deviation (SD) flares per month: 0.49 ± 1.52 in SMP/GMP/G60 group versus 0.70 ± 1.28 in control groups; mean difference (MD) -0.21, 95% confidence interval (CI) -0.76 to 0.34; low-quality evidence). The number of withdrawals due to adverse effects was similar in both groups although again the results were imprecise (7/40 in SMP/GMP/G600 group versus 11/80 in control groups; risk ratio (RR) 1.27, 95% CI 0.53 to 3.03; low-quality evidence). The findings for adverse events were also uncertain (2/40 in SMP/GMP/G600 group versus 3/80 in control groups; RR 1.33, 95% CI 0.23 to 7.66; low-quality evidence). Gastrointestinal events were the most commonly reported adverse effects. Pain from self reported gout flares (measured on a 10-point Likert scale) improved slightly more in the SMP/GMP/G600 group compared with controls (mean ± SD reduction -1.97 ± 2.28 points in SMP/GMP/G600 group versus -0.94 ± 2.25 in control groups; MD -1.03, 95% CI -1.96 to -0.10; low-quality evidence). This was an absolute reduction of 10% (95% CI 20% to 1% reduction), which may not be of clinical relevance. Results were imprecise for the outcome improvement in physical function (mean ± SD Health Assessment Questionnaire (HAQ)-II (scale 0 to 3, 0 = no disability): 0.08 ± 0.23 in SMP/GMP/G60 group versus 0.11 ± 0.31 in control groups; MD -0.03, 95% CI -0.14 to 0.08; low-quality evidence). Similarly, results for sUA reduction were imprecise (mean ± SD reduction: -0.025 ± 0.067 mmol/L in SMP/GMP/G60 group versus -0.010 ± 0.069 in control groups; MD -0.01, 95% CI -0.04 to 0.01; low-quality evidence). Th. While dietary supplements may be widely used for gout, this review has shown a paucity of high-quality evidence assessing dietary supplementation.

Topics: Adult; Allopurinol; Animals; Ascorbic Acid; Chronic Disease; Dietary Supplements; Gout; Humans; Lactose; Milk; Peptides; Powders; Randomized Controlled Trials as Topic

Incidence and prevalence of gout have markedly increased over the last few decades in keeping with the rise in prevalence of obesity and metabolic syndrome. Until recently, management of gout in patients with associated metabolic syndrome and comorbid illnesses such as renal impairment was difficult because of limited treatment options. However, significant progress has been made in the last few years, with introduction of new treatments such as interleukin-1 antagonists for management of acute gout, and febuxostat and pegloticase for chronic gout. The association of gout with alcohol, dietary purines and fructose ingestion has been confirmed in large prospective studies, thus enabling the clinician to now provide evidence-based advice to patients. Recent efficacy and safety data favour lower over higher doses of colchicine, and oral corticosteroids over non-steroidal anti-inflammatory drugs for patients with acute gout. Local ice therapy might help to differentiate gout from other forms of inflammatory arthritis, and supplementation with vitamin C help to reduce risk of gout. Several other drugs with rational mechanisms of action are in the pipeline, and likely to be introduced over the next few years. A new era has thus begun in the field of gout.

Topics: Adrenal Cortex Hormones; Alcohol Drinking; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Ascorbic Acid; Colchicine; Comorbidity; Cryotherapy; Diet; Dose-Response Relationship, Drug; Febuxostat; Fructose; Gout; Gout Suppressants; Humans; Interleukin 1 Receptor Antagonist Protein; Polyethylene Glycols; Purines; Receptors, Interleukin-1; Recombinant Fusion Proteins; Thiazoles; Urate Oxidase; Uric Acid; Uricosuric Agents; Vitamins; Xanthine Oxidase

Uric acid has historically been viewed as a purine metabolic waste product excreted by the kidney and gut that is relatively unimportant other than its penchant to crystallize in joints to cause the disease gout. In recent years, however, there has been the realization that uric acid is not biologically inert but may have a wide range of actions, including being both a pro- and anti-oxidant, a neurostimulant, and an inducer of inflammation and activator of the innate immune response. In this paper, we present the hypothesis that uric acid has a key role in the foraging response associated with starvation and fasting. We further suggest that there is a complex interplay between fructose, uric acid and vitamin C, with fructose and uric acid stimulating the foraging response and vitamin C countering this response. Finally, we suggest that the mutations in ascorbate synthesis and uricase that characterized early primate evolution were likely in response to the need to stimulate the foraging "survival" response and might have inadvertently had a role in accelerating the development of bipedal locomotion and intellectual development. Unfortunately, due to marked changes in the diet, resulting in dramatic increases in fructose- and purine-rich foods, these identical genotypic changes may be largely responsible for the epidemic of obesity, diabetes and cardiovascular disease in today's society.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Evolution, Molecular; Fasting; Fructose; Gout; Humans; Inflammation Mediators; Insulin Resistance; Metabolic Syndrome; Models, Biological; Starvation; Urate Oxidase; Uric Acid; Weight Gain

Hmong men in Minnesota exhibit a high prevalence of gout and hyperuricemia. Although evidence of vitamin C's effectiveness as a treatment for gout is mixed, analysis of therapeutic benefit based on an individual's multiomic signature may identify predictive markers of treatment success.. The primary objective of the Hmong Microbiome ANd Gout, Obesity, Vitamin C (HMANGO-C) study was to assess the effectiveness of vitamin C on serum urate in Hmong adults with and without gout/hyperuricemia. The secondary objectives were to assess if 1) vitamin C impacts the taxonomic and functional patterns of microbiota; 2) taxonomic and functional patterns of microbiota impact vitamin C's urate-lowering effects; 3) genetic variations impact vitamin C's urate-lowering effects; 4) differential microbial biomarkers exist for patients with or without gout; and 5) there is an association between obesity, gut microbiota and gout/hyperuricemia.. This prospective open-labelled clinical trial was guided by community-based participatory research principles and conducted under research safety restrictions for SARS-CoV-2. We aimed to enroll a convenient sample of 180 Hmong adults (120 with gout/hyperuricemia and 60 without gout/hyperuricemia) who provided medical, demographic, dietary and anthropometric information. Participants took vitamin C 500mg twice daily for 8 weeks and provided pre-and post- samples of blood and urine for urate measurements as well as stool samples for gut microbiome. Salivary DNA was also collected for genetic markers relevant to uric acid disposition.. We expected to quantify the impact of vitamin C on serum urate in Hmong adults with and without gout/hyperuricemia. The outcome will enhance our understanding of how gut microbiome and genomic variants impact the urate-lowering of vitamin C and associations between obesity, gut microbiota and gout/hyperuricemia. Ultimately, findings may improve our understanding of the causes and potential interventions that could be used to address health disparities in the prevalence and management of gout in this underserved population.. ClinicalTrials.gov NCT04938024 (first posted: 06/24/2021).

Topics: Adult; Ascorbic Acid; Clinical Trials, Phase II as Topic; COVID-19; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Microbiota; Obesity; Prospective Studies; SARS-CoV-2; Uric Acid; Vitamins

Short-term randomized trials suggest that a 500 mg/d vitamin C supplement reduces serum urate, whereas observational studies show vitamin E is inversely associated with gout risk.. We evaluated the effect of supplemental vitamin C (prespecified primary exposure) and vitamin E (prespecified secondary exposure) on new diagnoses of gout.. We performed a post hoc analysis of data from the Physicians' Health Study II, a randomized, double-blind, placebo-controlled factorial trial of randomized vitamin C (500 mg/d) and vitamin E (400 IU every other day). The primary outcome was new gout diagnoses, self-reported at baseline and throughout the follow-up period of ≤10 y.. Of 14,641 randomly assigned male physicians in our analysis, the mean age was 64 ± 9 y; 1% were Black, and 6.5% had gout prior to randomization. The incidence rate of new gout diagnoses during follow-up was 8.0 per 1000 person-years among those assigned vitamin C compared with 9.1 per 1000 person-years among those assigned placebo. The vitamin C assignment reduced new gout diagnoses by 12% (HR: 0.88; 95% CI: 0.77, 0.99; P = 0.04). These effects were greatest among those with a BMI <25 kg/m 2 (P-interaction = 0.01). Vitamin E was not associated with new gout diagnoses (HR: 1.05; 95% CI: 0.92, 1.19; P = 0.48).. Vitamin C modestly reduced the risk of new gout diagnoses in middle-aged male physicians. Additional research is needed to determine the effects of higher doses of vitamin C supplementation on serum urate and gout flares in adults with established gout.The Physicians' Health Study II is registered at clinicaltrials.gov (identifier: NCT00270647).

Topics: Adult; Aged; Ascorbic Acid; Dietary Supplements; Double-Blind Method; Gout; Humans; Male; Middle Aged; Physicians; Uric Acid; Vitamin E; Vitamins

Studies in human volunteers have shown that vitamin C reduces serum urate (SU) levels. The aim of this study was to determine the effects of vitamin C on SU levels in patients with gout.. Patients with gout and an SU level >0.36 mmoles/liter (6 mg/dl) were recruited. Twenty patients already taking allopurinol were randomized to receive an increase in the dose of allopurinol or to commence taking vitamin C (500 mg/day). Twenty patients who had not been taking allopurinol were randomized to start receiving either allopurinol (up to 100 mg/day) or vitamin C (500 mg/day). Levels of plasma ascorbate, creatinine, and SU were measured on day 0 and week 8.. There was no significant difference in the baseline SU level or estimated glomerular filtration rate (eGFR) between those who received vitamin C and those who did not (for SU, mean ± SEM 0.50 ± 0.11 mmoles/liter [8.4 ± 1.8 mg/dl] versus 0.50 ± 0.09 mmoles/liter [8.4 ± 1.5 mg/dl]; for eGFR, mean ± SEM 65.5 ± 3.5 ml/minute/1.73 m(2) versus 67.9 ± 4.6 ml/minute/1.73 m(2) ). Among the randomized patients, 30% in the vitamin C group and 25% in the no vitamin C control group were receiving diuretics. In the patients receiving vitamin C, there was a significant increase between day 0 and week 8 in the plasma ascorbate level. The reduction in SU level over 8 weeks was significantly less in those patients receiving vitamin C compared to those who started or increased the dose of allopurinol (mean reduction 0.014 mmoles/liter [0.23 mg/dl] versus 0.118 mmoles/liter [1.9 mg/dl]; P < 0.001).. A modest dosage of vitamin C (500 mg/day) for 8 weeks had no clinically significant urate-lowering effects in patients with gout, despite the fact that plasma ascorbate levels increased. These results differ from previous findings in healthy control subjects with hyperuricemia. The uricosuric effect of modest-dose vitamin C appears to be small in patients with gout, when administered as monotherapy or in combination with allopurinol.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Ascorbic Acid; Creatinine; Dietary Supplements; Female; Gout; Humans; Male; Middle Aged; New Zealand; Pilot Projects; Treatment Outcome; Uric Acid

This study investigated the effect of rebamipide on activation of the NLRP3 inflammasome and generation of reactive oxygen species (ROS) in monosodium urate (MSU) crystal-induced interleukin-1β (IL-1β) production. Human monocyte cell line THP-1 and human umbilical venous endothelial cells (HUVECs) were used to assess the inflammatory response to MSU crystals. NADP/NADPH activity assays were used as a marker of ROS generation. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to evaluate levels of IL-1β, caspase-1, NLRP3, associated speck-like protein (ASC), nuclear factor-κB (NF-κB), p65, IκBα, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Experimental pharmaceuticals included rebamipide, colchicine, dexamethasone, and ascorbic acid. In THP-1 cells, treatment with MSU crystals increased NADP/NADPH ratios and IL-1β expression, and both of these responses were potently inhibited by addition of rebamipide. Rebamipide also attenuated enhanced expression of caspase-1 gene by MSU crystals (p < 0.05). Western blotting demonstrated that MSU crystals stimulated caspase-1 but not NLRP3 and ASC activation. Similarly, MSU crystals activated the NF-κB pathway, which in turn was blocked by rebamipide. Stimulation of HUVECs with MSU crystals increased expression of VCAM-1 and ICAM-1, which were markedly inhibited by both rebamipide and dexamethasone. This study demonstrated that rebamipide inhibits IL-1β activation through suppression of ROS-mediated NF-κB signaling pathways and caspase-1 activation in MSU crystal-induced inflammation.

Topics: Alanine; Ascorbic Acid; Caspase 1; Cell Line; Colchicine; Dexamethasone; Enzyme Activation; Gout; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-1beta; NAD; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Quinolones; Reactive Oxygen Species; Signal Transduction; Uric Acid; Vascular Cell Adhesion Molecule-1

Topics: Antioxidants; Ascorbic Acid; Gout; Humans; Uric Acid

Topics: Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Febuxostat; Gout; Gout Suppressants; Humans; Thiazoles

Several metabolic studies and a recent double-blind, placebo-controlled, randomized trial have shown that higher vitamin C intake significantly reduces serum uric acid levels. Yet the relation with risk of gout is unknown.. We prospectively examined, from 1986 through 2006, the relation between vitamin C intake and risk of incident gout in 46 994 male participants with no history of gout at baseline. We used a supplementary questionnaire to ascertain the American College of Rheumatology criteria for gout. Vitamin C intake was assessed every 4 years through validated questionnaires.. During the 20 years of follow-up, we documented 1317 confirmed incident cases of gout. Compared with men with vitamin C intake less than 250 mg/d, the multivariate relative risk (RR) of gout was 0.83 (95% confidence interval [CI], 0.71-0.97) for total vitamin C intake of 500 to 999 mg/d, 0.66 (0.52-0.86) for 1000 to 1499 mg/d, and 0.55 (0.38-0.80) for 1500 mg/d or greater (P < .001 for trend). The multivariate RR per 500-mg increase in total daily vitamin C intake was 0.83 (95% CI, 0.77-0.90). Compared with men who did not use supplemental vitamin C, the multivariate RR of gout was 0.66 (95% CI, 0.49-0.88) for supplemental vitamin C intake of 1000 to 1499 mg/d and 0.55 (0.36-0.86) for 1500 mg/d or greater (P < .001 for trend).. Higher vitamin C intake is independently associated with a lower risk of gout. Supplemental vitamin C intake may be beneficial in the prevention of gout.

Topics: Adult; Aged; Ascorbic Acid; Gout; Humans; Incidence; Male; Middle Aged; Prospective Studies; Risk Factors; Surveys and Questionnaires; Uric Acid; Vitamins

Topics: Antioxidants; Ascorbic Acid; Citrus; Gout; Humans; Phytotherapy; Randomized Controlled Trials as Topic; Uric Acid; Vitamins

We examined associations between vitamin C intake and serum uric acid in men in a population-based study.. We included 1387 men without hypertension and with body mass index (BMI) < 30 kg/m(2) in the Health Professional Follow-up Study. Dietary intake was assessed with a semiquantitative food frequency questionnaire validated for use in this population. Serum uric acid concentrations were measured.. Greater intakes of total vitamin C were significantly associated with lower serum uric acid concentrations, after adjustment for smoking, BMI, ethnicity, blood pressure, presence of gout, use of aspirin, and intake of energy, alcohol, dairy protein, fructose, meat, seafood and coffee. An inverse dose-response association was observed through vitamin C intake of 400-500 mg/day, and then reached a plateau. Adjusted mean uric acid concentrations across total vitamin C intake categories (< 90, 90-249, 250-499, 500-999, or > or = 1000 mg/day) were 6.4, 6.1, 6.0, 5.7, and 5.7 mg/dl, respectively (p for trend < 0.001). Greater vitamin C intake was associated with lower prevalence of hyperuricemia (serum uric acid > 6 mg/dl). Multivariate odds ratios for hyperuricemia across total vitamin C intake categories were 1 (reference), 0.58, 0.57, 0.38, and 0.34 (95% CI 0.20-0.58; P for trend < 0.001). When we used dietary data, which were assessed 4-8 years before blood collection, as predictors, we observed similar inverse associations between vitamin C intake and uric acid.. These population-based data indicate that vitamin C intake in men is inversely associated with serum uric acid concentrations. These findings support a potential role of vitamin C in the prevention of hyperuricemia and gout.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Diet Surveys; Feeding Behavior; Gout; Humans; Hyperuricemia; Male; Middle Aged; Prospective Studies; Risk Factors; Surveys and Questionnaires; United States; Uric Acid

Topics: Allopurinol; Ascorbic Acid; Female; Fenofibrate; Gout; Gout Suppressants; Humans; Losartan; Male; Sensitivity and Specificity; Urate Oxidase; Uric Acid

Topics: Anemia, Hemolytic; Anemia, Hypochromic; Ascorbic Acid; Bilirubin; Blood Transfusion; Catalase; Chronic Disease; Glomerulonephritis; Gout; Hemoglobinometry; Humans; Iron; Kidney Diseases; Liver Diseases; Nephritis; Nitrogen; Rheumatic Fever; Surgical Procedures, Operative

Topics: Anticoagulants; Arthritis; Arthritis, Rheumatoid; Ascorbic Acid; Aspirin; Gout; Hip Joint; Humans; Joint Diseases; Rheumatology; Spondylitis; Spondylitis, Ankylosing

Topics: Antimalarials; Arthritis; Arthritis, Rheumatoid; Ascorbic Acid; Gout; Humans; Psoriasis; Spondylitis; Spondylitis, Ankylosing; Sunlight; Triamcinolone; Ultraviolet Rays; Vitamin A