Andrés Mariano, Sivera Francisca, Falzon Louise, Buchbinder Rachelle, Carmona Loreto
Sección de Reumatología, Hospital General Universitario de Alicante, C/ Pintor Baeza, 12, Alicante, Spain, 03010.
Cochrane Database Syst Rev. 2014 Oct 7(10):CD010156. doi: 10.1002/14651858.CD010156.pub2.
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). The study did not report tophus regression and health-related quality of life impact.One trial including 40 participants, at moderate to high risk of bias, compared vitamin C alone with allopurinol and with allopurinol plus vitamin C in a three-arm trial. We only compared vitamin C with allopurinol in this review. Participants were predominantly middle-aged men, and their severity of gout was representative of gout in general. The effect of vitamin C on the rate of gout attacks was not assessed. Vitamin C did not lower sUA as much as allopurinol (-0.014 mmol/L in vitamin C group versus -0.118 mmol/L in allopurinol group; MD 0.10, 95% CI 0.06 to 0.15; low-quality evidence). The study did not assess tophus regression, pain reduction or disability or health-related quality of life impact. The study reported no adverse events and no participant withdrawal due to adverse events.
AUTHORS' CONCLUSIONS: While dietary supplements may be widely used for gout, this review has shown a paucity of high-quality evidence assessing dietary supplementation.
膳食补充剂常用于治疗多种疾病,包括医生开处方使用或自行服用。然而,这些补充剂的益处和安全性证据通常有限或缺乏。
评估膳食补充剂对慢性痛风患者的疗效和安全性。
2013年6月6日,我们在Cochrane对照试验中心注册库(CENTRAL)、MEDLINE、EMBASE和CINAHL中进行了检索。我们未设置日期或语言限制。此外,我们还手工检索了2010年至2013年美国风湿病学会(ACR)和欧洲抗风湿病联盟(EULAR)会议的摘要,检查了所有纳入研究的参考文献和试验注册库。
我们纳入了所有已发表的随机对照试验(RCT)或半随机对照试验,这些试验比较了膳食补充剂与无补充剂、安慰剂、另一种补充剂或药物对成年慢性痛风患者的效果。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、益生元制剂、益生菌制剂和维生素。主要结局是痛风发作频率的降低以及因不良事件导致的试验参与者退出。我们还考虑了疼痛减轻、健康相关生活质量、血清尿酸(sUA)正常化、功能(即活动受限)、痛风石消退以及严重不良事件的发生率。
我们采用了Cochrane协作网预期的标准方法程序。
我们确定了两项符合纳入标准的RCT(160名参与者)。由于这两项试验评估了不同的饮食补充剂(富含糖巨肽的脱脂奶粉(SMP)和维生素C),且结果不同(富含SMP可预防痛风发作,维生素C可降低sUA),因此我们分别报告了结果。一项试验纳入了120名参与者,偏倚风险为中度,比较了富含糖巨肽(GMP)的SMP与未富集的SMP以及乳糖,为期三个月。参与者主要是50多岁患有严重痛风的男性。在研究期间,所有三组中以每月发作次数衡量的急性痛风发作频率均有所下降。三个月时,富含SMP(SMP/GMP/G600)与联合对照组(SMP和乳糖粉)相比,每月痛风发作的平均次数的影响尚不确定(SMP/GMP/G60组每月平均发作次数±标准差(SD):0.49±1.52,对照组为0.70±1.28;平均差值(MD)-0.21,95%置信区间(CI)-0.76至0.34;低质量证据)。两组因不良反应导致的退出人数相似,尽管结果同样不精确(SMP/GMP/G600组40人中有7人退出,对照组80人中有11人退出;风险比(RR)1.27,95%CI 0.53至3.03;低质量证据)。不良事件的结果也不确定(SMP/GMP/G600组40人中有2人出现不良事件,对照组80人中有3人出现;RR 1.33,95%CI 0.23至7.66;低质量证据)。胃肠道事件是最常报告的不良反应。与对照组相比,SMP/GMP/G600组自我报告的痛风发作疼痛(采用10分制李克特量表测量)改善幅度略大(SMP/GMP/G600组平均±SD降低-1.97±2.28分,对照组为-0.94±2.25分;MD -1.03,95%CI -1.96至-0.10;低质量证据)。这是绝对降低了10%(95%CI降低20%至1%),可能不具有临床相关性。身体功能改善结果不精确(SMP/GMP/G60组平均±SD健康评估问卷(HAQ)-II(0至3分,0=无残疾):0.08±0.23,对照组为0.11±0.31;MD -0.03,95%CI -0.14至0.08;低质量证据)。同样,sUA降低的结果也不精确(SMP/GMP/G60组平均±SD降低:-0.025±0.067 mmol/L,对照组为-0.010±0.069 mmol/L;MD -0.01,95%CI -0.04至0.01;低质量证据)。该研究未报告痛风石消退情况以及对健康相关生活质量的影响。一项试验纳入了40名参与者,偏倚风险为中度至高,在一项三臂试验中比较了单独使用维生素C与使用别嘌醇以及别嘌醇加维生素C的效果。在本综述中,我们仅比较了维生素C与别嘌醇的效果。参与者主要是中年男性,其痛风严重程度具有痛风的代表性。未评估维生素C对痛风发作率的影响。维生素C降低sUA的效果不如别嘌醇(维生素C组降低-0.014 mmol/L,别嘌醇组降低-0.118 mmol/L;MD 0.10,95%CI 0.06至0.15;低质量证据)。该研究未评估痛风石消退、疼痛减轻、残疾情况或对健康相关生活质量的影响。该研究未报告不良事件,也没有参与者因不良事件退出。
虽然膳食补充剂可能被广泛用于痛风治疗,但本综述表明评估膳食补充剂的高质量证据很少。