Table 2.
Meta-analysis of RCT of curcumin, curcuminoids, or turmeric in patients with triggering components in the origin of the MS (27, 28, 69–83).
| Author |
Diseases/
Focuses |
Design Study | Parameter Outcome | Significance on measured parameter | Heterogeneity result from meta-analysis | Subgroup analysis results |
|---|---|---|---|---|---|---|
| Sahebkar (80) | Healthy subjects and patients with chronic inflammatory disease | Systematic review and meta-analysis involving 8 RCTs | Total cholesterol LDL-C Triglycerides HDL-C |
Not significant Not significant Not significant Not significant |
I2 = 98%; P < 0.00 I2 = 99%; P < 0.00 I2 = 0%; P = 0.96 I2 = 90%; P < 0.00 |
Subgroup analysis of subjects with cardiovascular risk indicating similar significance on lipid profile, all with high heterogeneity, except for HDL-C (I2 = 0%) |
| Qin et al. (81) | Chronic inflammatory disease, including metabolic syndrome | Systematic review and meta-analysis involving 7 RCTs | LDL-C ↓* Triglycerides ↓ Total Cholesterol ↓ HDL-C |
Significant Significant Significant Not significant |
I2 = 42,1%; P < 0.125 I2 = 24.5%; P < 0.242 I2 = 73.8%; P < 0.054 I2 = 0,0%; P < 0.705 |
• Triglycerides did not change significantly in the turmeric powder subgroup compared to the mixture subgroup • In the hyperglycemia subgroup, there was no significant triglycerides reduction compared to the MS subgroup • All subgroup analyses reported high heterogeneity |
| de Melo ISV et al. (77) | Dysglycemia | Systematic review and meta-analysis, with 11 RCTs included | Fasting plasma glucose ↓ HbA1c ↓* |
Significant Significant |
All of the findings observed with high heterogeneity (I2 >50%, P < 0.05) |
• Fasting plasma glucose did not change significantly in non-diabetic subjects compared to subjects with prediabetes, diabetes, or MS • Fasting plasma glucose did not change significantly when using turmeric supplementation compared to curcumin and curcuminoids • HbA1c did not change significantly when using curcuminoids supplementation compared to curcumin supplementation • All subgroup analyses had high heterogeneity, except for fasting plasma glucose in non-diabetic subjects • Baseline blood glucose affected treatment effectiveness, the higher blood glucose baseline, the more effective the curcumin treatment |
| Mousavi et al. (82) | Chronic inflammatory disease including MS | Meta-analysis, involving 11 RCTs | Body weight ↓ | Significant BMI ↓* Waist circumference |
All of the findings observed with high heterogeneity (I2 >50%, P < 0.05) Significant Not significant |
• Curcumin dose of 1,000 mg/day for ≥8 weeks duration significantly reduced body weight and BMI in overweight subjects • All subgroup analyses had high heterogeneity |
| Qin et al. (70) | Chronic inflammatory disease including MS | Meta-analysis, involving 8 RCTs | MDA ↓* SOD ↑* |
Significant Significant |
All of the findings observed with high heterogeneity (I2 >50%, P < 0.05) | • The combination of curcuminoids and piperine lowered MDA • There is no significant difference in the improvement of MDA and SOD regardless of the associated disease, dose, and duration of administration • All subgroup analyses had low heterogeneity, except for osteoarthritis with regards to MDA level |
| Tabrizi et al. (27) | MS and its components, NAFLD, and coronary vascular artery | Systematic review and meta-analysis, 15 RCTs were included | IL-6 ↓* hscrp ↓* MDA ↓* TNF-alpha SOD Fasting plasma glucose ↓ |
Significant Significant Significant Not Significant Note Significant Significant |
All of the findings observed with high heterogeneity (I2 >50%, P < 0.05) | • None |
| Tabrizi et al. (27) | MS and its components, NAFLD, and coronary vascular artery | Systematic review and meta-analysis involving 26 RCTs | Fasting plasma glucose ↓ HbA1c ↓* HOMA-IR ↓* Triglycerides ↓ Total cholesterol ↓ Insulin ↑ |
Significant Significant Significant Significant Significant Significant Not Significant |
All of the findings observed with high heterogeneity (I2 >50%, P < 0.05) | • Curcumin in a dose of >500 mg/day supplemental dose for ≤ 8 weeks significantly improved total cholesterol and LDL-C in patients with a BMI ≥27, intervention subgroup • All subgroup analyses had high heterogeneity |
| LDL-C HDL-C |
Not Significant | |||||
| Akbari et al. (84) | MS and its components | Systematic review and meta-analysis involving 18 RCTs | BMI ↓* Waist circumference ↓ Weight ↓ Leptin ↓ Adiponectin ↑ Hip ratio |
Significant Significant Significants Significant Significant Not Significant |
I2 = 69,7%; P = 0.000 I2 = 45,7%; P = 0.027 I2 = 42,1%; P = 0,087 I2 = 0,0%; P = 0,613 I2 = 94,5%; P = 0,000 I2 = 0,00%; P = 0,792 |
• BMI, body weight, waist circumference, leptin, and adiponectin are consistently significant with >500 mg/day dose but some results (toward BMI and adiponectin) had high heterogeneity • BMI, body weight, waist circumference, leptin, and adiponectin showed various results regarding intervention duration, all with high heterogeneity, except for leptin • The hip ratio is not significantly affected by curcumin in all subgroups (regarding dose and duration) with low heterogeneity • Leptin is significantly affected in all subgroups (regarding dose and duration) with low heterogeneity |
| Azhdari et al. (28) | MS | Systematic review and meta-analysis involving 7 RCTs | Fasting plasma glucose ↓ Triglycerides ↓ HDL-C ↑* SBP DBP ↓* Waist circumference |
Significant Significant Significant Not Significant Significant Not Significant |
I2 = 90.1%; P = 0.00 I2 = 94.4%; P = 0.00 I2 = 98.6%; P = 0.00 I2 = 48.2%; P = 0.145 I2 = 48.7%; P = 0.142 I2 = 0.00%; P = 0.595 |
• No available subgroup analysis due to lack of trials |
| Clark et al. (26) | Prediabetes and type 2 diabetes mellitus | Systematic review and meta-analysis involving 6 RCTs | Adiponectin ↑ | Significant | I2 = 87.2%; P = 0.00 | • Curcumin significantly improved adiponectin in <10-week intervention duration subgroup (I2 = 49,5%) |
| Hadi et al. (78) | Improvement of blood pressure parameters | Systematic review and meta-analysis, 11 RCTs were included | SBP DBP |
Not significant, with only−1.24 mmHg reduction Not significant |
I2 = 0% I2 = 1% |
• Significant SBP lowering effect with ≥12-week intervention, without clinically significant effect (overall only 1,24 mmHg reduction of SBP) |
| Huang et al. (76) | Chronic inflammatory disease, including MS | Meta-analysis, involving 14 RCTs | Fasting plasma glucose ↓ HbA1c ↓* HOMA-IR ↓* |
Significant Significant Significant |
All findings had high heterogeneity (I2 >50%, P < 0.05) | • Significant results of improved fasting plasma glucose and HbA1c were found in patients with diabetes treated with ≥300 mg/day for ≥12 weeks • All subgroup analyses had low heterogeneity, except for HbA1c correlation in the ≥12 weeks subgroup |
| Simental-Mendía LE et al. (79) | Healthy subjects and patients with chronic inflammatory disease | Systematic review and meta-analysis involving 20 RCTs | Triglycerides ↓ HDL-C ↑* Total cholesterol LDL-C |
Significant Significant Not Significant Not Significant |
I2 = 65.55% I2 = 37.24% I2 = 84.25% I2 = 85.64% |
• No significant difference was observed regarding the duration of curcuminoid supplementation on all lipid parameters • There was no significant effect of curcumin on HDL-C in both of <12-week and ≥12-week intervention subgroups |
| White et al. (72) | Chronic inflammatory disease, including MS, and cardiovascular diseases | Systematic review and meta-analysis, involving 19 RCTs | CRP, hscrp, IL-1β, IL-6, and TNF-α* | Not significant | All findings had high heterogeneity (I2 >50%, P < 0.05), except for hsCRP (I2 = 21%)() | • No conclusive heterogeneity source, the details were not mentioned |
| Yuan et al. (83) | Chronic inflammatory disease, including | Systematic review and meta-analysis involving 16 RCTs | Triglycerides ↓ Total Cholesterol ↓ LDL-C ↓* HDL-C ↑* |
Significant Significant Significant Significant |
I2 = 75%; P < 0.00 I2 = 48%; P < 0.00 I2 = 71%; P < 0.00 I2 = 70%; P < 0.00 |
• More significant reduction in triglycerides observed in ≥1,000 mg/day dose than the low dose (I2 = 77% in high dose vs. 43% in low dose group) |
| metabolic syndrome | • Higher reduction of LDL-C was found in ≥300 mg/day supplemental dose compared to low dose (I2 = 55% vs. 80%) • The effectiveness of triglyceride reduction was observed at 24-week, 12-week, and 8-week intervention, therefore, triglyceride might be lowered with a minimum of 8-week intervention (I2 <50%) • There was no significant improvement in triglyceride, LDL-C, HDL-C, and total cholesterol at 4-weeks. LDL-C and total cholesterol-lowering effect required 12-week intervention (I2 = 0 for all measurements) • There was no significant improvement of HDL-C with 8-week intervention duration, low dose (≥300 mg/day), and in non-diabetic subjects (I2 = 53% vs. 0% vs. 53% respectively) • There was heterogeneity among the subgroup analyses. All blood lipid results had low heterogeneity with a minimum 12-week intervention duration. High dose intervention and subjects with diabetes type 2 had lower total cholesterol with low heterogeneity. |
|||||
| Altobelli et al. (75) | Uncomplicated type 2 diabetes | Meta-analysis involving 7 RCTs | HbA1c ↓* HOMA-IR ↓* LDL-C ↓* BMI HDL-C Triglycerides ↓ Total Cholesterol ↓ |
Significant Significant Significant Not Significant Not Significant Significant Significant |
I2 = 42.42%; P = 0.107 I2 = 0.00%; P = 0.916 I2 = 0.00%; P = 0.083 I2 = 0.00%; P = 0.514 I2 = 0.00%; P = 0.116 I2 = 41.56%; P = 0.144 I2 = 0.00%; P = 0.573 |
• Low heterogeneity, no need to subgroup |
| Ferguson et al. (69) | Healthy subjects and patients with chronic inflammatory disease | Systematic review and meta-analysis involving 32 RCTs | CRP ↓* | Significant | I2 >50%, P < 0.05 | • Bio-enhanced curcuminoids led to the greatest reduction of CRP, followed by non-bio-enhanced curcuminoids, bio-enhanced curcumin, curcumin (without regards to bio-enhancement), and turmeric consecutively. Regarding CRP measurement, the only low heterogeneity result was observed for the curcuminoid non-bio-enhanced group. |
| IL-6 | Significant | I2 >50%, P < 0.05 | • Bio-enhanced curcuminoids led to the greatest reduction of IL-6, followed by non-bio-enhanced curcuminoids, bio-enhanced curcumin, and curcumin consecutively. Turmeric had no effect and curcumin (regardless of bio-enhancement) and bio-enhanced curcumin significantly lowered IL-6 with low heterogeneity, meanwhile, other results had high heterogeneity. | |||
| TNF-α* | Significant | I2 >50%, P < 0.05 | • Bio-enhanced curcuminoids led to the greatest reduction of TNF-α compared to bio-enhanced curcumin | |||
| Gorabi et al. (73) | Inflammatory diseases, including MS and its components | Meta-analysis involving 32 RCTs | IL-1 ↓* TNF-α ↓* IL-6 IL-8 |
Significant Significant Not Significant Not Significant |
All findings had high heterogeneity (I2 >50%, P < 0.05) | • TNF-α was significantly decreased with a curcumin dose of <1,000 mg/day • TNF-α was significantly decreased with ≥10 weeks of curcumin supplementation • All subgroup analyses had high heterogeneity |
CRP, C-Reactive Protein; hs-CRP, high-sensitivity C-reactive protein; IL-1, Interleukin 1; TNF-α, Tumor Necrosis Factor – α; IL-6, Interleukin 6; IL-8, Interleukin 8; MDA, malondialdehyde; SBP, Systolic Blood Pressure; DBP, Diastolic Blood Pressure; HbA1c, glycosylated hemoglobin; SOD, superoxide dismutase; LDL-C, Low Density Lipoprotein 264 Cholesterol; HDL-C, High Density Lipoprotein Cholesterol; BMI, Body Mass Index; HOMA-IR, Homeostatic Model Assessment of Insulin Resistance.