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19 curcumin COVID-19 controlled studies, 15 RCTs
https://c19curcumin.com/meta.html
• Statistically significant improvements are seen for
mortality ,
hospitalization ,
recovery , and
viral clearance . 11 studies from 10 independent teams in 6 different countries show statistically significant
improvements in isolation (7 for the most serious outcome).
• Results are robust — in exclusion sensitivity analysis 15 of 19
studies must be excluded to avoid finding statistically significant efficacy
in pooled analysis.
• Studies typically use advanced formulations for greatly improved bioavailability.
• While
many treatments have some level
of efficacy, they do not replace vaccines and other measures to avoid
infection.
Only 26% of curcumin
studies show zero events in the treatment arm.
Multiple treatments are typically used
in combination, and
other treatments
may be more effective.
• No treatment, vaccine, or intervention is 100%
available and effective for all variants. All practical, effective, and safe
means should be used.
Denying the efficacy of treatments increases mortality, morbidity, collateral
damage, and endemic risk.
• All data to reproduce this paper and
sources are in the
appendix .
Other meta analyses for curcumin can be found in
[Kow , Vahedian-Azimi ] , showing significant improvements for mortality, hospitalization, and symptoms.
Highlights
We show traditional outcome specific analyses and combined
evidence from all studies, incorporating treatment delay, a primary
confounding factor in COVID-19 studies.
A
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Dound (RCT) 33%
0.67 [0.54-0.82]
6 pt. scale
100 (n)
100 (n)
CT1
Improvement, RR [CI] Treatment Control Saber-Moghaddam 94%
0.06 [0.00-0.93]
progression
0/21
8/20
Pawar (DB RCT) 82%
0.18 [0.04-0.79]
death
2/70
11/70
Ahmadi (DB RCT) 86%
0.14 [0.01-2.65]
hosp.
0/30
3/30
Sankhe (RCT) 89%
0.11 [0.01-2.03]
death
0/87
4/87
CT1
Majeed (DB RCT) 66%
0.34 [0.01-8.09]
ventilation
0/45
1/47
CT1
Khan (RCT) 33%
0.67 [0.37-1.19]
no recov.
10/25
15/25
CT1
Askari (DB RCT) -125%
2.25 [0.30-16.6]
no recov.
3/8
1/6
Tau2 = 0.10, I2 = 29.6%, p = 0.0092
Early treatment 46%
0.54 [0.34-0.86]
15/386
43/385
46% improvement Valizadeh (DB RCT) 50%
0.50 [0.18-1.40]
death
4/20
8/20
Improvement, RR [CI] Treatment Control Tahmasebi (DB RCT) 83%
0.17 [0.02-1.32]
death
1/40
6/40
Hassania.. (DB RCT) -46%
1.46 [0.01-329]
SpO2 imp.
20 (n)
20 (n)
Asadirad (RCT) 26%
0.74 [0.26-2.12]
death
5/27
6/24
Kartika 41%
0.59 [0.35-1.00]
hosp. time
139 (n)
107 (n)
Hartono (RCT) 53%
0.47 [0.32-0.68]
viral+
14/30
30/30
CT1
Thomas (DB RCT) 44%
0.56 [0.34-0.91]
improv.
74 (n)
73 (n)
LONG COVID CT1
Sankhe (SB RCT) 86%
0.14 [0.01-2.71]
death
0/60
3/60
CT1
Hellou (DB RCT) 77%
0.23 [0.06-0.95]
NEWS2
33 (n)
17 (n)
CT1
Tau2 = 0.00, I2 = 0.0%, p < 0.0001
Late treatment 49%
0.51 [0.40-0.64]
24/443
53/391
49% improvement Shehab 42%
0.58 [0.14-2.32]
severe case
2/32
24/221
Improvement, RR [CI] Treatment Control Nimer 31%
0.69 [0.45-1.04]
hosp.
29/329
179/1,819
Tau2 = 0.00, I2 = 0.0%, p = 0.039
Prophylaxis 32%
0.68 [0.48-0.98]
31/361
203/2,040
32% improvement All studies 40%
0.60 [0.52-0.69]
70/1,190
299/2,816
40% improvement 19 curcumin COVID-19 studies c19curcumin.com Aug 2022
Tau2 = 0.00, I2 = 0.0%, p < 0.0001
Effect extraction pre-specified (most serious outcome, see appendix) 1 CT: study uses combined treatment Favors curcumin
Favors control
B
C
Figure 1. A. Random effects
meta-analysis. This plot shows pooled effects, discussion can be found in the heterogeneity section,
and results for specific outcomes can be found in the individual outcome analyses.
Effect extraction is pre-specified, using the most serious outcome reported.
For details of effect extraction see the
appendix .
B. Scatter plot showing the
distribution of effects reported in studies.
C. History of all reported
effects (chronological within treatment stages).
Introduction
We analyze all significant studies
concerning the use of
curcumin
for COVID-19.
Search methods, inclusion criteria, effect
extraction criteria (more serious outcomes have priority), all individual
study data, PRISMA answers, and statistical methods are detailed in
Appendix 1 . We present random effects meta-analysis results for all
studies, for studies within each treatment stage, for individual outcomes, for
peer-reviewed studies, for Randomized Controlled Trials (RCTs), and after
exclusions.
Figure 2 shows stages of possible treatment for
COVID-19.
Prophylaxis refers to regularly taking medication before
becoming sick, in order to prevent or minimize infection.
Early
Treatment refers to treatment immediately or soon after symptoms appear,
while
Late Treatment refers to more delayed treatment.
Mechanisms of Action
3CLpro inhibitor Curcumin inhibits SARS-CoV-2 3CLpro [Bahun , Guijarro-Real , Rehman ] .
RdRp inhibitor SARS-CoV-2 RNA‐dependent RNA polymerase (RdRp) inhibition [Singh ] .
ACE2 inhibitor Curcumin inhibits ACE2 activity. SARS-CoV-2 viral entry requires host cell surface proteins ACE2 and TMPRSS2 [Jena , Patel ] .
TMPRSS2 downregulation Curcumin downregulates transmembrane serine protease 2 (TMPRSS2). SARS-CoV-2 viral entry requires host cell surface proteins ACE2 and TMPRSS2 [Goc ] .
Cathepsin L inhibitor Curcumin inhibits cathepsin L activity. Cathepsin L plays a key role in viral entry [Goc ] .
Anti‑inflammatory Curcumin shows anti-inflammatory effects [Daily , Derosa , Gupta , Marín-Palma , Rattis , Sahebkar ] .
Inhibition in Vero E6 cells demonstrated In Vitro research shows curcumin inhibits SARS-CoV-2 in Vero E6 cells [Bormann , Marín-Palma ] .
Inhibition in Calu-3 cells demonstrated In Vitro research shows curcumin inhibits SARS-CoV-2 in Calu-3 cells [Bormann ] .
Preclinical and Phase I Research
[Panda ] present a phase I clinical study investigating a
novel formulation of curcumin that may be more effective for COVID-19.
Preclinical research is an important part of the development of
treatments, however results may be very different in clinical trials.
Preclinical results are not used in this paper.
Results
Figure 3 shows a visual overview of the results, with details in
Table 2 and
Table 3 .
Figure
4 ,
5 ,
6 ,
7 ,
8 ,
9 ,
10 ,
11 , and
12
show forest plots for a random effects meta-analysis of
all studies with pooled effects, mortality results, ventilation, ICU admission, hospitalization, progression, recovery, viral clearance, and peer reviewed studies.
0
0.5
1
1.5+
ALL STUDIES
MORTALITY
VENTILATION
ICU ADMISSION
HOSPITALIZATION
PROGRESSION
RECOVERY
VIRAL CLEARANCE
RANDOMIZED CONTROLLED TRIALS
RCT MORTALITY
PEER-REVIEWED
After Exclusions
ALL STUDIES
All
Prophylaxis
Early
Late
Curcumin for COVID-19
C19CURCUMIN.COM AUG 2022
Treatment time Number of studies reporting positive effects
Total number of studies Percentage of studies reporting positive effects
Random effects meta-analysis results
Early treatment
7
8
87.5%
46% improvement
Late treatment
8
9
88.9%
49% improvement
Prophylaxis
2
2
100%
32% improvement
All studies
17
19
89.5%
40% improvement
Table 2. Results by treatment stage.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Dound (RCT) 33%
0.67 [0.54-0.82]
6 pt. scale
100 (n)
100 (n)
CT1
Improvement, RR [CI] Treatment Control Saber-Moghaddam 94%
0.06 [0.00-0.93]
progression
0/21
8/20
Pawar (DB RCT) 82%
0.18 [0.04-0.79]
death
2/70
11/70
Ahmadi (DB RCT) 86%
0.14 [0.01-2.65]
hosp.
0/30
3/30
Sankhe (RCT) 89%
0.11 [0.01-2.03]
death
0/87
4/87
CT1
Majeed (DB RCT) 66%
0.34 [0.01-8.09]
ventilation
0/45
1/47
CT1
Khan (RCT) 33%
0.67 [0.37-1.19]
no recov.
10/25
15/25
CT1
Askari (DB RCT) -125%
2.25 [0.30-16.6]
no recov.
3/8
1/6
Tau2 = 0.10, I2 = 29.6%, p = 0.0092
Early treatment 46%
0.54 [0.34-0.86]
15/386
43/385
46% improvement Valizadeh (DB RCT) 50%
0.50 [0.18-1.40]
death
4/20
8/20
Improvement, RR [CI] Treatment Control Tahmasebi (DB RCT) 83%
0.17 [0.02-1.32]
death
1/40
6/40
Hassania.. (DB RCT) -46%
1.46 [0.01-329]
SpO2 imp.
20 (n)
20 (n)
Asadirad (RCT) 26%
0.74 [0.26-2.12]
death
5/27
6/24
Kartika 41%
0.59 [0.35-1.00]
hosp. time
139 (n)
107 (n)
Hartono (RCT) 53%
0.47 [0.32-0.68]
viral+
14/30
30/30
CT1
Thomas (DB RCT) 44%
0.56 [0.34-0.91]
improv.
74 (n)
73 (n)
LONG COVID CT1
Sankhe (SB RCT) 86%
0.14 [0.01-2.71]
death
0/60
3/60
CT1
Hellou (DB RCT) 77%
0.23 [0.06-0.95]
NEWS2
33 (n)
17 (n)
CT1
Tau2 = 0.00, I2 = 0.0%, p < 0.0001
Late treatment 49%
0.51 [0.40-0.64]
24/443
53/391
49% improvement Shehab 42%
0.58 [0.14-2.32]
severe case
2/32
24/221
Improvement, RR [CI] Treatment Control Nimer 31%
0.69 [0.45-1.04]
hosp.
29/329
179/1,819
Tau2 = 0.00, I2 = 0.0%, p = 0.039
Prophylaxis 32%
0.68 [0.48-0.98]
31/361
203/2,040
32% improvement All studies 40%
0.60 [0.52-0.69]
70/1,190
299/2,816
40% improvement 19 curcumin COVID-19 studies c19curcumin.com Aug 2022
Tau2 = 0.00, I2 = 0.0%, p < 0.0001
Effect extraction pre-specified (most serious outcome, see appendix) 1 CT: study uses combined treatment Favors curcumin
Favors control
Figure 4. Random effects meta-analysis for all studies with pooled effects.
This plot shows pooled effects, discussion can be found in the heterogeneity section,
and results for specific outcomes can be found in the individual outcome analyses.
Effect extraction is pre-specified, using the most serious outcome reported.
For details of effect extraction see the
appendix .
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Pawar (DB RCT) 82%
0.18 [0.04-0.79]
2/70
11/70
Improvement, RR [CI] Treatment Control Sankhe (RCT) 89%
0.11 [0.01-2.03]
0/87
4/87
CT1
Tau2 = 0.00, I2 = 0.0%, p = 0.007
Early treatment 84%
0.16 [0.04-0.61]
2/157
15/157
84% improvement Valizadeh (DB RCT) 50%
0.50 [0.18-1.40]
4/20
8/20
Improvement, RR [CI] Treatment Control Tahmasebi (DB RCT) 83%
0.17 [0.02-1.32]
1/40
6/40
Asadirad (RCT) 26%
0.74 [0.26-2.12]
5/27
6/24
Sankhe (SB RCT) 86%
0.14 [0.01-2.71]
0/60
3/60
CT1
Tau2 = 0.00, I2 = 0.0%, p = 0.038
Late treatment 51%
0.49 [0.25-0.96]
10/147
23/144
51% improvement All studies 61%
0.39 [0.21-0.71]
12/304
38/301
61% improvement 6 curcumin COVID-19 mortality results c19curcumin.com Aug 2022
Tau2 = 0.00, I2 = 0.0%, p = 0.0021
1 CT: study uses combined treatment Favors curcumin
Favors control
Figure 5. Random effects meta-analysis for mortality results.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Sankhe (RCT) 75%
0.25 [0.03-2.19]
1/87
4/87
CT1
Improvement, RR [CI] Treatment Control Majeed (DB RCT) 66%
0.34 [0.01-8.09]
0/45
1/47
CT1
Tau2 = 0.00, I2 = 0.0%, p = 0.16
Early treatment 72%
0.28 [0.05-1.65]
1/132
5/134
72% improvement Sankhe (SB RCT) 86%
0.14 [0.01-2.71]
0/60
3/60
CT1
Improvement, RR [CI] Treatment Control Tau2 = 0.00, I2 = 0.0%, p = 0.2
Late treatment 86%
0.14 [0.01-2.71]
0/60
3/60
86% improvement All studies 77%
0.23 [0.05-1.06]
1/192
8/194
77% improvement 3 curcumin COVID-19 mechanical ventilation results c19curcumin.com Aug 2022
Tau2 = 0.00, I2 = 0.0%, p = 0.06
1 CT: study uses combined treatment Favors curcumin
Favors control
Figure 6. Random effects meta-analysis for ventilation.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Sankhe (SB RCT) 67%
0.33 [0.04-3.11]
1/60
3/60
CT1
Improvement, RR [CI] Treatment Control Tau2 = 0.00, I2 = 0.0%, p = 0.34
Late treatment 67%
0.33 [0.04-3.11]
1/60
3/60
67% improvement All studies 67%
0.33 [0.04-3.11]
1/60
3/60
67% improvement 1 curcumin COVID-19 ICU result c19curcumin.com Aug 2022
Tau2 = 0.00, I2 = 0.0%, p = 0.34
1 CT: study uses combined treatment Favors curcumin
Favors control
Figure 7. Random effects meta-analysis for ICU admission.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Saber-Moghaddam 45%
0.55 [0.39-0.79]
hosp. time
21 (n)
20 (n)
Improvement, RR [CI] Treatment Control Ahmadi (DB RCT) 86%
0.14 [0.01-2.65]
hosp.
0/30
3/30
Sankhe (RCT) 10%
0.90 [0.71-1.15]
hosp. time
87 (n)
87 (n)
CT1
Majeed (DB RCT) 80%
0.20 [0.01-4.13]
hosp.
0/45
2/47
CT1
Tau2 = 0.09, I2 = 57.4%, p = 0.09
Early treatment 33%
0.67 [0.42-1.06]
0/183
5/184
33% improvement Kartika 41%
0.59 [0.35-1.00]
hosp. time
139 (n)
107 (n)
Improvement, RR [CI] Treatment Control Sankhe (SB RCT) 10%
0.90 [0.71-1.15]
hosp. time
45 (n)
45 (n)
CT1
Hellou (DB RCT) 13%
0.87 [0.07-10.6]
hosp. time
33 (n)
17 (n)
CT1
Tau2 = 0.00, I2 = 2.8%, p = 0.12
Late treatment 17%
0.83 [0.66-1.05]
0/217
0/169
17% improvement Nimer 31%
0.69 [0.45-1.04]
hosp.
29/329
179/1,819
Improvement, RR [CI] Treatment Control Tau2 = 0.00, I2 = 0.0%, p = 0.054
Prophylaxis 31%
0.69 [0.45-1.04]
29/329
179/1,819
31% improvement All studies 25%
0.75 [0.62-0.90]
29/729
184/2,172
25% improvement 8 curcumin COVID-19 hospitalization results c19curcumin.com Aug 2022
Tau2 = 0.02, I2 = 29.6%, p = 0.0023
1 CT: study uses combined treatment Favors curcumin
Favors control
Figure 8. Random effects meta-analysis for hospitalization.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Saber-Moghaddam 94%
0.06 [0.00-0.93]
0/21
8/20
Improvement, RR [CI] Treatment Control Tau2 = 0.00, I2 = 0.0%, p = 0.044
Early treatment 94%
0.06 [0.00-0.93]
0/21
8/20
94% improvement Asadirad (RCT) 50%
0.50 [0.14-1.82]
3/30
6/30
Improvement, RR [CI] Treatment Control Tau2 = 0.00, I2 = 0.0%, p = 0.3
Late treatment 50%
0.50 [0.14-1.82]
3/30
6/30
50% improvement All studies 76%
0.24 [0.03-1.80]
3/51
14/50
76% improvement 2 curcumin COVID-19 progression results c19curcumin.com Aug 2022
Tau2 = 1.11, I2 = 47.5%, p = 0.17
Favors curcumin
Favors control
Figure 9. Random effects meta-analysis for progression.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Saber-Moghaddam 38%
0.62 [0.39-0.96]
no recov.
11/21
17/20
Improvement, RR [CI] Treatment Control Ahmadi (DB RCT) 21%
0.79 [0.48-1.31]
recov. time
30 (n)
30 (n)
Sankhe (RCT) 46%
0.54 [0.35-0.76]
no recov.
29/87
60/87
CT1
Majeed (DB RCT) 43%
0.57 [0.39-0.84]
no recov.
45 (n)
47 (n)
CT1
Khan (RCT) 33%
0.67 [0.37-1.19]
no recov.
10/25
15/25
CT1
Askari (DB RCT) -125%
2.25 [0.30-16.6]
no recov.
3/8
1/6
Tau2 = 0.00, I2 = 0.0%, p < 0.0001
Early treatment 39%
0.61 [0.51-0.74]
53/216
93/215
39% improvement Hassania.. (DB RCT) -46%
1.46 [0.01-329]
SpO2 imp.
20 (n)
20 (n)
Improvement, RR [CI] Treatment Control Asadirad (RCT) 45%
0.55 [0.27-1.09]
no recov.
8/27
13/24
Sankhe (SB RCT) 32%
0.68 [0.54-0.86]
recov. time
45 (n)
45 (n)
CT1
Hellou (DB RCT) 77%
0.23 [0.06-0.95]
NEWS2
33 (n)
17 (n)
CT1
Tau2 = 0.00, I2 = 0.0%, p < 0.0001
Late treatment 35%
0.65 [0.53-0.81]
8/125
13/106
35% improvement All studies 37%
0.63 [0.55-0.72]
61/341
106/321
37% improvement 10 curcumin COVID-19 recovery results c19curcumin.com Aug 2022
Tau2 = 0.00, I2 = 0.0%, p < 0.0001
1 CT: study uses combined treatment Favors curcumin
Favors control
Figure 10. Random effects meta-analysis for recovery.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Majeed (DB RCT) 6%
0.94 [0.80-1.10]
viral time
45 (n)
47 (n)
CT1
Improvement, RR [CI] Treatment Control Khan (RCT) 50%
0.50 [0.30-0.84]
viral+
10/25
20/25
CT1
Tau2 = 0.16, I2 = 80.9%, p = 0.3
Early treatment 28%
0.72 [0.39-1.33]
10/70
20/72
28% improvement Hartono (RCT) 53%
0.47 [0.32-0.68]
viral+
14/30
30/30
CT1
Improvement, RR [CI] Treatment Control Sankhe (SB RCT) 44%
0.56 [0.38-0.81]
viral load
44 (n)
43 (n)
CT1
Hellou (DB RCT) 10%
0.90 [0.47-1.71]
viral+
14/33
8/17
CT1
Tau2 = 0.03, I2 = 33.3%, p = 0.00045
Late treatment 43%
0.57 [0.42-0.78]
28/107
38/90
43% improvement All studies 35%
0.65 [0.45-0.93]
38/177
58/162
35% improvement 5 curcumin COVID-19 viral clearance results c19curcumin.com Aug 2022
Tau2 = 0.12, I2 = 78.4%, p = 0.017
1 CT: study uses combined treatment Favors curcumin
Favors control
Figure 11. Random effects meta-analysis for viral clearance.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Dound (RCT) 33%
0.67 [0.54-0.82]
6 pt. scale
100 (n)
100 (n)
CT1
Improvement, RR [CI] Treatment Control Saber-Moghaddam 94%
0.06 [0.00-0.93]
progression
0/21
8/20
Pawar (DB RCT) 82%
0.18 [0.04-0.79]
death
2/70
11/70
Ahmadi (DB RCT) 86%
0.14 [0.01-2.65]
hosp.
0/30
3/30
Sankhe (RCT) 89%
0.11 [0.01-2.03]
death
0/87
4/87
CT1
Majeed (DB RCT) 66%
0.34 [0.01-8.09]
ventilation
0/45
1/47
CT1
Khan (RCT) 33%
0.67 [0.37-1.19]
no recov.
10/25
15/25
CT1
Askari (DB RCT) -125%
2.25 [0.30-16.6]
no recov.
3/8
1/6
Tau2 = 0.10, I2 = 29.6%, p = 0.0092
Early treatment 46%
0.54 [0.34-0.86]
15/386
43/385
46% improvement Valizadeh (DB RCT) 50%
0.50 [0.18-1.40]
death
4/20
8/20
Improvement, RR [CI] Treatment Control Tahmasebi (DB RCT) 83%
0.17 [0.02-1.32]
death
1/40
6/40
Hassania.. (DB RCT) -46%
1.46 [0.01-329]
SpO2 imp.
20 (n)
20 (n)
Asadirad (RCT) 26%
0.74 [0.26-2.12]
death
5/27
6/24
Hartono (RCT) 53%
0.47 [0.32-0.68]
viral+
14/30
30/30
CT1
Thomas (DB RCT) 44%
0.56 [0.34-0.91]
improv.
74 (n)
73 (n)
LONG COVID CT1
Sankhe (SB RCT) 86%
0.14 [0.01-2.71]
death
0/60
3/60
CT1
Hellou (DB RCT) 77%
0.23 [0.06-0.95]
NEWS2
33 (n)
17 (n)
CT1
Tau2 = 0.00, I2 = 0.0%, p < 0.0001
Late treatment 51%
0.49 [0.37-0.63]
24/304
53/284
51% improvement Shehab 42%
0.58 [0.14-2.32]
severe case
2/32
24/221
Improvement, RR [CI] Treatment Control Nimer 31%
0.69 [0.45-1.04]
hosp.
29/329
179/1,819
Tau2 = 0.00, I2 = 0.0%, p = 0.039
Prophylaxis 32%
0.68 [0.48-0.98]
31/361
203/2,040
32% improvement All studies 
