Sección de Reumatología, Hospital General Universitario de Alicante, Alicante, Spain.
Departamento de Medicina Clínica, Universidad Miguel Hernández, Elche, Spain.
Cochrane Database Syst Rev. 2021 Nov 12;11(11):CD010156. doi: 10.1002/14651858.CD010156.pub3.
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 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.
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.
We used standard methodological procedures expected by Cochrane.
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.
膳食补充剂常用于治疗多种医学病症,包括医生开具处方或患者自行使用的补充剂。然而,这些补充剂的益处和安全性的证据通常是有限的或不存在的。
评估慢性痛风患者使用膳食补充剂的疗效和安全性。
我们通过检索 CENTRAL、MEDLINE、Embase、CINAHL 和四个试验注册库(2020 年 8 月)对原始研究进行了更新。我们没有对日期或语言进行限制。我们还对 2010 年至 2019 年美国风湿病学会和欧洲抗风湿病联盟会议的摘要进行了手工检索,并检查了所有纳入研究的参考文献。
我们考虑了所有发表的随机对照试验(RCT)或准 RCT,这些试验将膳食补充剂与无补充剂、安慰剂、另一种补充剂或药物治疗慢性痛风的成年患者进行了比较。膳食补充剂包括但不限于氨基酸、抗氧化剂、必需矿物质、多不饱和脂肪酸、前体药物、益生菌和维生素。主要结局是急性痛风发作、因不良反应(AE)而退出研究、血清尿酸(sUA)降低、关节疼痛减轻、患者总体评估、总不良反应数和痛风石消退。
我们使用了符合 Cochrane 预期的标准方法学程序。
两项先前纳入的 RCT(160 名参与者)符合我们的纳入标准;我们没有发现任何新的试验用于本次更新。由于这两项试验评估了不同的饮食补充剂(富含糖巨肽的浓缩乳粉(SMP)和维生素 C),且结局不同(SMP 预防富含 GMP 的 SMP 痛风发作,维生素 C 降低 sUA),我们分别报告了结果。一项试验(120 名参与者),存在选择和检测偏倚的风险不明确,将富含糖巨肽的 SMP 与未富含 SMP 的 SMP 和乳糖进行了比较,为期三个月。参与者主要是男性,年龄在 50 多岁,患有严重的痛风。除了疼痛外,所有主要结局的结果都不精确,也没有临床意义。在三个月的研究期间,所有三组的痛风发作次数(每月发作次数)均减少。在三个月时,与联合对照组(SMP 和乳糖粉)相比,富含 SMP(SMP/GMP/G600)的 Mean(SD)每月痛风发作次数无临床意义差异(每月发作次数:SMP/GMP/G60 组 0.49(1.52),对照组 0.70(1.28);绝对风险差异:MD 每月发作次数减少 0.21,95%置信区间(CI)为 0.76 至 0.34;低质量证据)。因不良反应而退出研究的人数在两组之间相似(SMP/GMP/G600 组 7/40,对照组 11/80;RR 1.27,95%CI 0.53 至 3.03;低质量证据);SMP/乳糖组有 4%更多的退出人数(18%到 2%的减少;低质量证据)。血清尿酸降低在两组之间相似(SMP/GMP/G60 组 Mean(SD)-0.025(0.067)mmol/L,对照组-0.010(0.069)mmol/L;MD-0.01,95%CI-0.04 至 0.01;低质量证据)。自我报告的痛风发作疼痛(用 10 分制 Likert 量表测量)在富含 GMP 的 SMP 组中比对照组略有改善(SMP/GMP/G600 组 Mean(SD)-1.97(2.28),对照组-0.94(2.25);MD-1.03,95%CI-1.89 至-0.17)。这是一个绝对减少了 10%(95%CI 20%到 1%的减少;低质量证据),可能没有临床意义。不良反应的风险在两组之间相似(SMP/GMP/G600 组 19/40,对照组 39/80;RR 0.97,95%CI 0.66 至 1.45);绝对风险差异为不良反应减少 1%(1%到 2%的增加),低质量证据)。胃肠道事件,如恶心、腹胀和腹泻,是最常见的不良反应。关于患者总体评估的数据无法进行分析;该研究未报告痛风石消退情况。一项试验(40 名参与者),存在选择、执行和检测偏倚的高风险,将维生素 C 单独与别嘌呤醇进行了比较,并与别嘌呤醇加维生素 C 进行了三臂研究。我们只将维生素 C 与别嘌呤醇比较的数据纳入了本次综述。参与者主要是中年男性,他们的痛风严重程度代表了一般痛风的情况。与维生素 C 相比,别嘌呤醇降低 sUA 水平更多(MD 0.10mmol/L,95%CI 0.06 至 0.15),低质量证据。该研究报告无不良反应;没有参与者因不良反应而退出。该研究没有评估痛风发作频率、关节疼痛减轻、患者总体评估或痛风石消退情况。
虽然膳食补充剂可能被广泛用于痛风,但本综述未发现高质量的证据支持或反驳富含糖巨肽的浓缩乳粉或维生素 C 用于慢性痛风患者。