Abstract: 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. While dietary supplements may be widely used for gout, this review has shown a paucity of high-quality evidence assessing dietary supplementation.

Plain-language summary: After searching the medical literature up to 6 June 2013 we found two studies The first study (120 participants) compared enriched skim milk powder (with peptides with probable anti-inflammatory effect) to standard skim milk and to lactose powder, and the second study (40 participants) compared vitamin C with allopurinol - a drug commonly used in gout. In the first study, the enriched milk aimed to reduce the frequency of gout attacks, while in the second study the vitamin C aimed to reduce the uric acid levels in blood. People with gout enrolled in both studies were predominantly middle-aged men; in the skim milk study, participants with gout appeared severe as they had very frequent attacks and 20% to 43% presented with tophi, while in the vitamin C study, participants appeared similar to ordinary participants with gout. Gout attacks People who consumed enriched skim milk powder had 0.21 fewer gout attacks per month at three months (from 0.76 fewer to 0.34 more), or 2.5 fewer gout attacks per year: - People who consumed enriched skim milk powder had 0.49 gout attacks per month (or six gout attacks per year). - People who consumed standard skim milk powder or lactose had 0.70 gout attacks per month (or eight gout attacks per year). Withdrawals due to adverse events 4 more people out of 100 who consumed enriched skim milk powder discontinued the supplement at three months (4% more withdrawals). - 18 out of 100 stopped consuming enriched skim milk powder. - 14 out of 100 stopped consuming standard skim milk powder or lactose. Pain reduction, serum uric acid (sUA) levels and physical function were uncertain. Effect on tophus regression was not measured. Serum uric acid levels - People who consumed vitamin C showed an sUA level reduction of 0.014 mmol/L after eight weeks (or 2.8% sUA reduction) - People who were administered allopurinol showed an sUA level reduction of 0.118 mmol/L after eight weeks (or 23.6% sUA reduction). There were no reports of side effects or withdrawals due to side effects in the vitamin C or allopurinol treatment groups. Effects of vitamin C on gout attacks, pain reduction, physical function and tophus regression were not measured. Low-quality evidence from one study indicated enriched skim milk, compared with standard skim milk or lactose powder, may not reduce the frequency of gout attacks or improve physical function or uric acid levels, but may reduce pain. Further research is likely to change these estimates. We do not have precise information about side effects and complications, but possible side effects may include nausea or diarrhoea. Compared with the commonly used medicine allopurinol, low-quality evidence from one study indicated the effect of vitamin C in reducing sUA levels is smaller and probably clinically unimportant. Other possible benefits of vitamin C are uncertain, as they were not evaluated in the study. No side effects were reported. Further research is likely to change these estimates.