Silymarin Supplementation in Active Rheumatoid Arthritis: Outcomes of a Pilot Randomized Controlled Clinical Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Study Design
2.3. Outcomes
2.4. Patients’ Evaluation
2.5. Statistical Analysis
3. Results
3.1. Patients’ Characteristics
3.2. Indicators of Disease Activity
3.3. Inflammatory Markers
3.4. Disease Activity Indices
3.5. Disability Index
3.6. EULAR Responses
3.7. Fatigue, Depression, and Anxiety
3.8. Impact of Silymarin Supplementation on Patients’ General Condition
3.9. Correlations between Disease Severity, Functional Status and Levels of Fatigue, Depression and Anxiety
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variable | Control Group (n = 61) | Intervention Group (n = 61) | p Value |
---|---|---|---|
Age (years) (95% CI) | 9.92 (56.36–61.44) | 8.19 (55.11–59.31) | 0.308 a |
Gender (Female) | 51 (49.5%) | 52 (50.5%) | 0.803 b |
Gender (Male) | 10 (52.6%) | 9 (47.4%) | |
Residence (Rural) | 29 (47.5%) | 32 (52.5%) | 0.587 b |
Residence (Urban) | 32 (52.5%) | 29 (47.5%) | |
Height (cm) (95% CI) | 8.08 (163.60–167.74) | 7.43 (161.90–165.71) | 0.186 a |
Weight (kg) (95% CI) | 15.87 (72.82–80.95) | 13.19 (70.57–77.33) | 0.269 a |
BMI (kg/m2) (95% CI) | 5.51 (26.62–29.44) | 4.55 (26.36–28.69) | 0.587 a |
Smoker | 7 (50%) | 7 (50%) | 0.611 b |
Nonsmoker | 55 (50%) | 54 (50%) | |
No. of comorbidities (95% CI) | 1.45 (1.99–2.73) | 1.38 (2.06–2.76) | 0.848 a |
Disease duration (years) (95% CI) | 5.53 (5.53–8.37) | 5.08 (5.27–7.87) | 0.696 a |
Disease stage (I/II) | 28 (45.9%) | 27 (44.3%) | 0.856 b |
Disease stage (III/IV) | 33 (54.1%) | 34 (55.7%) | |
Functional Capacity (I/II) | 55 (90.2%) | 56 (91.8%) | 0.752 b |
Functional Capacity (III/IV) | 6 (9.8%) | 5 (8.2%) | |
Autoantibodies | |||
RF (IU/mL) (95% CI) | 168.46 (42.12–132.35) | 220.35 (54.84–169.69) | 0.497 a |
ANA (U/mL) (95% CI) | 1.23 (0.40–1.04) | 1.16 (0.33–0.94) | - |
DNAds (U/mL) (95% CI) | 14.18 ± 22.81 (8.23–20.12) | 13.50 ± 21.01 (8.03–18.98) | - |
ACPA (U/mL) (95% CI) | 252.49 ± 386.11 (151.87–353.11) | 238.06 ± 386.85 (137.28–338.85) | - |
Outcome | Control Group | Intervention Group | p Value |
---|---|---|---|
TJC28 | |||
Baseline (95% CI) | 5.89 (18.19–21.34) | 4.31 (18.94–21.19) | 0.755 a |
Week 8 (95% CI) | 5.05 (20.03–22.73) | 3.68 (8.62–10.54) | 0.000 a |
Change | 2.94 | 3.87 | - |
p value | 0.000 b | 0.000 b | - |
SJC28 | |||
Baseline (95% CI) | 4.63 (11.33–13.81) | 3.26 (11.84–13.54) | 0.868 a |
Week 8 (95% CI) | 5.13 (12.20–14.95) | 2.42 (3.34–4.60) | 0.000 a |
Change | 2.87 | 3.48 | - |
p value | 0.012 b | 0.000 b | - |
Morning stiffness (min.) | |||
Baseline (95% CI) Week 8 (95% CI) Change p value | 21.20 (30.30–41.66) 16.34 (34.55–43.30) 11.94 0.070 b | 20.97 (30.64–41.57) 15.23 (23.99–31.93) 19.67 0.002 b | 0.976 a 0.000 a - - |
Pain intensity (cm) | |||
Baseline (95% CI) | 1.48 (7.21–8.00) | 1.29 (6.63–7.30) | 0.015 a |
Week 8 (95% CI) | 1.25 (7.54–8.21) | 1.29 (3.22–3.89) | 0.000 a |
Change | 0.94 | 1.12 | - |
p value | 0.038 b | 0.000 b | - |
PtGA | |||
Baseline (95% CI) | 1.48 (7.21–8.00) | 1.29 (6.63–7.30) | 0.015 a |
Week 8 (95% CI) | 1.25 (7.54–8.21) | 1.29 (3.22–3.89) | 0.000 a |
Change | 0.94 | 1.12 | - |
p value | 0.038 b | 0.000 b | - |
PhGA | |||
Baseline (95% CI) | 1.48 (7.21–8.00) | 1.29 (6.63–7.30) | 0.015 a |
Week 8 (95% CI) | 1.29 (7.51–8.20) | 1.29 (3.22–3.89) | 0.000 a |
Change | 0.94 | 1.12 | - |
p value | 0.051 b | 0.001 b | - |
Outcome | Control Group | Intervention Group | p Value |
---|---|---|---|
ESR (mm/h) | |||
Baseline (95% CI) | 27.05 (24.24–38.73) | 15.74 (20.00–28.20) | 0.075 a |
Week 8 (95% CI) | 23.41 (22.18–34.72) | 15.07 (19.95–27.81) | 0.220 a |
Change | 18.90 | 9.32 | - |
p value | 0.235 b | 0.857 b | - |
CRP (mg/dL) | |||
Baseline (95% CI) Week 8 (95% CI) Change p value | 4.45 (0.97–3.35) 2.27 (0.84–2.05) 4.06 0.191 b | (0.63–1.32) (0.80–1.33) 0.632 b | 0.060 a 0.253 a - - |
Outcome | Control Group | Intervention Group | p Value |
---|---|---|---|
DAS28 (ESR) | |||
Baseline (95% CI) | 1.03 (6.41–6.96) | 0.67 (6.36–6.71) | 0.378 a |
Week 12 (95% CI) | 0.97 (6.56–7.08) | 0.84 (4.60–5.04) | 0.000 a |
Change | −0.14 ± 0.61 | 0.61 | - |
p value | 0.094 b | 0.000 b | - |
DAS28 (CRP) | |||
Baseline (95% CI) | 0.89 (6.01–6.49) | 0.63 (5.94–6.72) | 0.311 a |
Week 12 (95% CI) | 0.83 (6.18–6.63) | 0.83 (4.21–4.64) | 0.000 a |
Change | −0.15 ± 0.58 | 0.70 | - |
p value | 0.094 b | 0.000 b | - |
SDAI | |||
Baseline (95% CI) | 14.58 (46.52–54.33) | 8.51 (45.45–49.89) | 0.222 a |
Week 12 (95% CI) | 12.68 (48.77–55.57) | 8.58 (19.20–23.67) | 0.000 a |
Change | 9.35 | 8.20 | - |
p value | 0.169 b | 0.000 b | - |
CDAI | |||
Baseline (95% CI) | 13.05 (44.77–51.76) | 8.30 (44.53–48.86) | 0.445 a |
Week 12 (95% CI) | 11.93 (47.58–53.97) | 8.07 (18.27–22.47) | 0.000 a |
Change | 7.40 | 7.88 | - |
p value | 0.014 b | 0.000 b | - |
HAQ-DI | |||
Baseline (95% CI) | 0.45 (1.88–2.12) | 0.45 (1.78–2.02) | 0.212 a |
Week 12 (95% CI) | 0.39 (2.06–2.27) | 0.36 (1.08–1.27) | 0.000 a |
Change | 0.25 | 0.31 | - |
p value | 0.000 b | 0.000 b | - |
Outcome | Control Group | Intervention Group | p Value |
---|---|---|---|
VAS-F | |||
Baseline (95% CI) | 12.90 (68.15–75.06) | 11.88 (67.67–73.86) | 0.716 a |
Week 8 (95% CI) | 10.61 (72.52–78.20) | 10.39 (35.09–40.50) | 0.000 a |
Change | 11.25 | 13.55 | - |
p value | 0.016 b | 0.000 b | - |
BDI-II | |||
Baseline (95% CI) | 6.78 (17.67–21.30) | 5.64 (16.56–19.50) | 0.215 a |
Week 8 (95% CI) | 5.15 (19.83–22.59) | 3.48 (7.99–9.81) | 0.000 a |
Change | 3.62 | 3.73 | - |
p value | 0.001 b | 0.000 b | - |
GAD-7 | |||
Baseline (95% CI) | 3.59 (10.09–12.02) | 4.17 (9.61–11.78) | 0.623 a |
Week 8 (95% CI) | 2.79 (11.36–12.86) | 2.01 (3.02–4.07) | 0.000 a |
Change | 2.22 | 3.41 | - |
p value | 0.001 b | 0.000 b | - |
Group | DAS28- ESR | DAS28- CRP | SDAI | CDAI | HAQ-DI | VAS-F | BDI-II | GAD-7 | |
---|---|---|---|---|---|---|---|---|---|
DAS28-ESR | I | 0.836 | 0.858 | 0.838 | 0.426 | 0.466 | 0.180 | 0.159 | |
(0.000) | (0.000) | (0.000) | (0.001) | (0.000) | (0.172) | (0.229) | |||
C | 0.824 | 0.757 | 0.667 | 0.305 | 0.316 | 0.250 | 0.243 | ||
(0.000) | (0.000) | (0.000) | (0.022) | (0.018) | (0.063) | (0.071) | |||
DAS28-CRP | I | 0.866 | 0.824 | 0.401 | 0.506 | 0.251 | 0.126 | ||
(0.000) | (0.000) | (0.002) | (0.000) | (0.055) | (0.342) | ||||
C | 0.790 | 0.685 | 0.210 | 0.306 | 0.328 | 0.211 | |||
(0.000) | (0.000) | (0.121) | (0.022) | (0.014) | (0.118) | ||||
SDAI | I | 0.987 | 0.353 | 0.494 | 0.200 | 0.159 | |||
(0.000) | (0.006) | (0.000) | (0.128) | (0.229) | |||||
C | 0.908 | 0.279 | 0.225 | 0.165 | 0.162 | ||||
(0.000) | (0.038) | (0.096) | (0.225) | (0.234) | |||||
CDAI | I | 0.357 | 0.505 | 0.185 | 0.164 | ||||
(0.005) | (0.000) | (0.161) | (0.213) | ||||||
C | 0.294 | 0.191 | 0.097 | 0.193 | |||||
(0.028) | (0.159) | (0.476) | (0.154) | ||||||
HAQ-DI | I | 0.387 | 0.442 | 0.437 | |||||
(0.002) | (0.000) | (0.001) | |||||||
C | 0.271 | 0.288 | 0.211 | ||||||
(0.044) | (0.032) | (0.118) | |||||||
VAS-F | I | 0.423 | 0.419 | ||||||
(0.001) | (0.001) | ||||||||
C | 0.394 | 0.389 | |||||||
(0.003) | (0.003) | ||||||||
BDI-II | I | 0.651 | |||||||
(0.000) | |||||||||
C | 0.618 | ||||||||
(0.000) |
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Zugravu, G.S.; Pintilescu, C.; Cumpat, C.-M.; Miron, S.D.; Miron, A. Silymarin Supplementation in Active Rheumatoid Arthritis: Outcomes of a Pilot Randomized Controlled Clinical Study. Medicina 2024, 60, 999. https://doi.org/10.3390/medicina60060999
Zugravu GS, Pintilescu C, Cumpat C-M, Miron SD, Miron A. Silymarin Supplementation in Active Rheumatoid Arthritis: Outcomes of a Pilot Randomized Controlled Clinical Study. Medicina. 2024; 60(6):999. https://doi.org/10.3390/medicina60060999
Chicago/Turabian StyleZugravu, Georgeta Stefanovici, Carmen Pintilescu, Carmen-Marinela Cumpat, Sorin Dan Miron, and Anca Miron. 2024. "Silymarin Supplementation in Active Rheumatoid Arthritis: Outcomes of a Pilot Randomized Controlled Clinical Study" Medicina 60, no. 6: 999. https://doi.org/10.3390/medicina60060999