PMID- 34767649 OWN - NLM STAT- MEDLINE DCOM- 20211206 LR - 20240426 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 11 IP - 11 DP - 2021 Nov 12 TI - Dietary supplements for chronic gout. PG - CD010156 LID - 10.1002/14651858.CD010156.pub3 [doi] LID - CD010156 AB - BACKGROUND: 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. OBJECTIVES: To assess the efficacy and safety of dietary supplementation for people with chronic gout. SEARCH METHODS: We updated the original search by searching CENTRAL, MEDLINE, Embase, CINAHL, and four trials registers (August 2020). We applied no date or language restrictions. We also handsearched the abstracts from the 2010 to 2019 American College of Rheumatology and European League against Rheumatism conferences, and checked the references of all included studies. SELECTION CRITERIA: 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 major outcomes were acute gout flares, study withdrawal due to adverse events (AEs), serum uric acid (sUA) reduction, joint pain reduction, participant global assessment, total number of AEs, and tophus regression. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: Two previously included RCTs (160 participants) met our inclusion criteria; we did not identify any new trials for this update. 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 (120 participants), at unclear risk of selection and detection bias, compared SMP enriched with glycomacropeptides (GMP) with un-enriched SMP, and with lactose, over three months. Participants were predominantly men, aged in their 50s, who had severe gout. The results for all major outcomes were imprecise, except for pain. None of the results were clinically significant. The frequency of acute gout attacks, measured as the number of flares per month, decreased in all three groups over the three-month 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 not clinically significant (mean (standard deviation (SD)) flares per month: 0.49 (1.52) in SMP/GMP/G60 group versus 0.70 (1.28) in the control groups; absolute risk difference: mean difference (MD) -0.21 flares per month, 95% confidence interval (CI) -0.76 to 0.34; low-quality evidence). The number of withdrawals due to adverse effects was similar between groups (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); there were 4% more withdrawals in the SMP/lactose groups (10% fewer to 18% more; low-quality evidence). Serum uric acid reduction was similar across groups (mean (SD) -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). Pain from self-reported gout flares (measured on a 10-point Likert scale) improved slightly more in the GMP/G600 SMP group compared with controls (mean (SD) -1.97 (2.28) in SMP/GMP/G600 group versus -0.94 (2.25) in control groups; MD -1.03, 95% CI -1.89 to -0.17). This was an absolute reduction of 10% (95% CI 20% to 1% reduction; low-quality evidence), which may not be of clinical relevance. The risk of adverse events was similar between groups (19/40 in SMP/GMP/G600 group versus 39/80 in control groups; RR 0.97, 95% CI 0.66 to 1.45); the absolute risk difference was 1% fewer adverse events (1% fewer to 2% more), low-quality evidence). Gastrointestinal events such as nausea, flatulence and diarrhoea were the most commonly reported adverse effects. Data for participant global assessment were not available for analysis; the study did not report tophus regression. One trial (40 participants), at high risk of selection, performance, and detection bias, compared vitamin C alone with allopurinol, and with allopurinol plus vitamin C, in a three-arm study. We only included data from the vitamin C versus allopurinol comparison in this review. Participants were predominantly middle-aged men, and their severity of gout was representative of gout in general. Allopurinol reduced sUA levels more than vitamin C (MD 0.10 mmol/L, 95% CI 0.06 to 0.15), low-quality evidence. The study reported no adverse events; none of the participants withdrew due to adverse events. The study did not assess the rate of gout attacks, joint pain reduction, participant global assessment, or tophus regression. AUTHORS' CONCLUSIONS: While dietary supplements may be widely used for gout, this review found no high-quality that supported or refuted the use of glycomacropeptide-enriched skim milk powder or vitamin C for adults with chronic gout. CI - Copyright (c) 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. FAU - Andres, Mariano AU - Andres M AD - Seccion de Reumatologia, Hospital General Universitario de Alicante, Alicante, Spain. AD - Departamento de Medicina Clinica, Universidad Miguel Hernandez, Elche, Spain. FAU - Sivera, Francisca AU - Sivera F AD - Departamento de Medicina Clinica, Universidad Miguel Hernandez, Elche, Spain. AD - Servicio de Reumatologia, Hospital de Elda, Elda (Alicante), Spain. FAU - Buchbinder, Rachelle AU - Buchbinder R AD - Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University; Monash-Cabrini Department of Musculoskeletal Health and Clinical Epidemiology, Cabrini Health, Melbourne, Australia. FAU - Pardo Pardo, Jordi AU - Pardo Pardo J AD - Ottawa Hospital Research Institute, The Ottawa Hospital - General Campus, Ottawa, Canada. FAU - Carmona, Loreto AU - Carmona L AD - Instituto de Salud Musculoesqueletica, Madrid, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PT - Systematic Review DEP - 20211112 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 0 (Powders) RN - 63CZ7GJN5I (Allopurinol) SB - IM UOF - Cochrane Database Syst Rev. 2014 Oct 07;(10):CD010156. PMID: 25287939 MH - Adult MH - Aged MH - Allopurinol MH - Animals MH - Dietary Supplements MH - *Gout/drug therapy MH - Humans MH - Male MH - Middle Aged MH - Milk MH - Powders PMC - PMC8589461 COIS- MA: from Grunenthal, honoraria for consultancy (January 2017), lectures (November 2018), and travel expenses to attend 2017 EULAR meeting; from Menarini, honoraria for lecture (2019); from Horizon, honoraria for consultancy (June 2017); and from Astra-Zeneca, honoraria for consultancy (2015), and travel expenses to attend 2015 ACR meeting. None of these laboratories manufacture diet supplements or allopurinol. FS: received honoraria for consultancy from Abbvie, Pfizer, Grunenthal, and MSD; payment for lectures from Grunenthal; and travel expenses from Novartis, Pfizer, and Abbvie. Her institution also received grants from Roche, Novartis, and Sandoz. LC: has no conflicts of interest with the producers or providers of products appearing in the review; however, her institution provided consultant services for studies and educational activities to all the producers of potential drugs to include in the review: Grunenthal (to analyse a database and draft a manuscript on gout mortality in 2018), SOBI (The Spanish Society of Paediatric Rheumatology, via a grant from SOBI, in 2016 to 2017 to run a national registry on JIA-Still's), and Novartis (in 2018 to 2020 to finance online courses to medical specialists on research methodology). LC has not personally benefited from these funds. RB: is the Co-ordinating Editor of Cochrane Musculoskeletal but is not involved in editorial decisions regarding this review. She is the recipient of a National Health and Medical Research Council (NHMRC) Cochrane Collaboration Round 7 Funding Program Grant, which supports the activities of Cochrane Musculoskeletal Australia and Cochrane Australia, but the funding source did not participate in the conduct of this review. JPP: none known EDAT- 2021/11/13 06:00 MHDA- 2021/12/15 06:00 PMCR- 2022/11/12 CRDT- 2021/11/12 17:18 PHST- 2021/11/12 17:18 [entrez] PHST- 2021/11/13 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2022/11/12 00:00 [pmc-release] AID - CD010156.pub3 [pii] AID - 10.1002/14651858.CD010156.pub3 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2021 Nov 12;11(11):CD010156. doi: 10.1002/14651858.CD010156.pub3.