Table 2.
Randomized controlled studies of effects of single nutrients or antioxidants on Disease Activity Score in Rheumatoid Arthritis.
| Author, Year, Country (Ref) | Participants | Population | Study Duration | Intervention | Control | DAS28 Main Results | Adjusted Analysis | Study Quality | Comments |
|---|---|---|---|---|---|---|---|---|---|
| Galarraga 2008UK (Scotland) [28] RCT DB |
N randomized: 97N intervention: 49 N control: 48 Total drop out: 40% |
71% women 77% DMARD use Disease activity: Intermediate |
12 weeks | 10 g cod liver oil in capsules containing: 1500 mg EPA, 700 mg DHA, 800 µg vit A, 5 µg vit D, 20 IE vit E | Placebo (air filled capsules) | DAS28 CRP: I: 4.5 → 4.3 C: 4.5 → 4.3 P = 0.976 |
Unadjusted | B | Study duration was 9 mo but after 12 w NSAID was reduced Amount of n3/d unclear No drop out analysis High drop out |
| Das Gupta 2009 Bangladesh [29] RCT UB |
N randomized: 100N intervention: 50 N control: 50 Total drop out: 19% |
% of women not specified % MTX use not specified Disease activity: High |
12 weeks | 75 mg/d indomethacin 3 g/d n3 FA in capsules |
75 mg/d indomethacin | DAS28: I: 7.2 → 4.2 C: 7.3 → 4.8 P < 0.05 |
Unadjusted | B | No clear aim or hypothesis No clear description of participant characteristics Calculation of DAS28 unclear |
| Dawczynski 2018 Germany [30] RCOT DB |
N randomized: 38N intervention: 38 N control: 38 Total drop out: 34% |
84% women % MTX use not specified Disease activity: Intermediate |
10 weeks | 8 g micro algae, enriched in 60 g sausage, 8 g tomato spread, 30 g milk powder Amount of n3/d: 2.36 g |
8 g sun flower oil, enriched in 60 g sausage, 8 g tomato spread, 30 g milk powder | DAS28: I: 4.5 → 3.88 C: 3.99 → 4.13 P = 0.085 |
Adjusted for sequence and baseline value | B | Excluded those with poor compliance Calculation of DAS28 unclear |
| Dawczynski 2009 Germany [31] RCOT UB |
N randomized: 45N intervention: 45 N control: 45 Total drop out: 13% |
96% women % MTX use not specified Disease activity: Intermediate |
12 weeks |
40 g fat in the form of 200 g yoghurt, 30 g cheese and butter. Milk fat was in part exchanged with oils high in EPA, DHA and alpha linoleic acid. Amount of n3/d: 2.4 g |
Commercial dairy products with similar fat content | DAS28: I: 4.45 → 4.32 C: 4.18 → 4.24 P = NS |
Adjusted for sequence and baseline value | B | Excluded those with poor compliance Adjusted for potential carry over effects in analysis Calculation of DAS28 unclear No relevant power calculation |
| Remans2004 Netherlands [32] RCT DB |
N randomized: 66N intervention: 33 N control: 33 Total drop out: 17% |
82% women 62% MTX use Disease activity: High |
4 months | Liquid nutritional supplement containing PUFA (1400 mg EPA 211 mg DHA, 40 mg DPA, 16 mg ALA) and micronutrients | Placebo drink with the same taste, odor and color but with artificial sweetener | DAS28: I: 5.36 → 5.58 C: 5.14 → 5.35 P = NS |
Unadjusted | B | Slight gain in body weight in intervention group Calculation of DAS28 unclear No drop out analysis |
| Buondonno 2017 Italy [33] RCT DB |
N randomized: 39 N intervention: 21 N control: 18 Total drop out: 8% |
100% women 100% MTX use Disease activity: High |
3 months | 300 000 IU (7500 µg) of vitamin D3 administered once | Placebo | DAS28 ESR: I: ? → 5.6 C: ? →5.8 P = NS |
Unadjusted | B | Unclear DAS28 at baseline No dropout analysis, but low drop out |
| Hansen 2014 USA [34] RCT DB |
N randomized: 22 N intervention: 11 N control: 11 Total drop out: 0% |
46% women % MTX use not specified Disease activity: Low |
12 months | Month 1: 3*50 000 IU vitamin D2/week Month 2-11: 2*50 000 IU vitamin D2/month 1500 mg calcium daily |
Placebo 1500 mg calcium daily |
DAS28: I: 3.0 → 3.03 C: 2.54 → 2.96 P = NS |
Unadjusted | C | Sparse methods and results No relevant power calculation Calculation of DAS28 not presented |
| Rastmanesh 2008 Iran [35] RCT DB |
N randomized: 38N intervention: 18 N control: 18 Total drop out: 16% |
100% women 100% DMARD use Disease activity: High |
28 days | 6000 mg of potassium in the form of enriched white grape juice | Placebo grape juice | DAS28: I: 5.86 → −0.69 C: 5.80 → −0.1 P < 0.01 |
Adjusted for baseline | B | Hypokalemic participants Short study duration Calculation of DAS28 unclear Compliance unclear Conflict of interest statement missing |
| Shishavan 2015 Iran [36] RCT DB |
N randomized: 64N intervention: 32 N control: 32 Total drop out: 9% |
100% women 91% MTX use Disease activity: Remission |
8 weeks | 10 µg/day of vitamin K1 as a chewable tablet | Placebo | DAS28 CRP: I: 1.74 → 1.59 C: 2.26 → 1.85 P = NS |
Adjusted (baseline, duration, folic acid intake, energy intake and weight) | A | No drop out analysis, but few drop outs Participants in remission at baseline |
| Van Ede 2001 Netherlands [37] RCT DB |
N randomized: 434N intervention 1: 143 N intervention 2: 147 N control: 144 Total drop out unclear |
71% women 100% MTX use Disease activity: Intermediate |
12 months | Intervention 1: 1 mg/day of folic acid (oral, intake in morning) Intervention 2: 2.5 mg/week of folinic acid (oral, within 24 h of MTX intake) |
Placebo | DAS28 ESR: I 1: 4.8 → −1.5 I 2: 4.6 → −1.4 C: 4.7 → −1.5 P1 = NS P2 = NS |
Unadjusted? | B | Drop out unclear Unclear if analysis is adjusted |
| Gargari 2015 Iran [38] RCT DB |
N randomized: 70N intervention: 35 N control: 35 Total drop out: 7% |
100% women 88% MTX use Disease activity: Remission |
8 weeks | Two capsules of 1200 mg alpha lipoic acid | Placebo (1200 mg maltodextrin) | DAS28: I: 2.11 → 1.86 C: 2.14 → 1.98 P = 0.442 |
Adjusted for baseline value | A | Excluded those with poor compliance, but few No dropout analysis, but few dropouts Participants in remission at baseline Calculation of DAS28 unclear |
| Javadi 2016 Iran [39] RCT DB |
N randomized: 50N intervention: 25 N control: 25 Total drop out: 20% |
100% women 92% MTX use Disease activity: Low–intermediate |
8 weeks | One capsule containing 500 mg quercetin | Placebo (lactose) | DAS28 ESR: I: 3.22 → 2.65 C: 3.13 → 3.11 P = 0.04 |
Adjusted for baseline value | B | Conflict of interest statement missing No drop out analysis Excluded those with poor compliance |
| Nachvak 2019 Iran [40] RCT DB |
N randomized: 54N intervention: 27 N control: 27 Total drop out: 17% |
89% women % MTX use not specified Disease activity: Intermediate |
2 months | 100 mg/day CoQ10 capsules | Placebo | DAS28 ESR: I: 5.01→2.34 C: 4.88→4.04 P < 0.001 |
Adjusted for baseline, age, sex, disease duration, medications, and total energy intake | B | Compliance unclear No drop out analysis Placebo unclear |
| Khojah 2018 Egypt [41] RCT UB |
N randomized: 100N intervention: 50 N control: 50 Total drop out: 0% |
68% women % MTX use not specified Disease activity: Intermediate |
3 months | One capsule containing 1 g resveratrol daily | Regular treatment | DAS28 ESR: I: 4.62 → 3.12 C: 4.91 → 4.78 P < 0.001 |
Unadjusted | B | No placebo No relevant power analysis Compliance unclear |
RCT; randomized controlled trial, RCOT; randomized crossover trial, UB; unblinded, SB; single blind, DB; double blind, N; number, MTX; metrotrexate, ITT; Intention to treat.