Curcumin for COVID-19: real-time analysis of all 39 studies

Curcumin for COVID-19: real-time meta analysis of 21 studies

Covid Analysis (Preprint) (meta analysis)

• 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).

• Meta analysis using the most serious outcome reported shows 39% [31‑46%] improvement. Results are similar for Randomized Controlled Trials, similar after exclusions, and similar for peer-reviewed studies.

• Results are robust — in exclusion sensitivity analysis 17 of 21 studies must be excluded to avoid finding statistically significant efficacy in pooled analysis.

• Studies typically use advanced formulations for greatly improved bioavailability.

• No treatment, vaccine, or intervention is 100% effective and available. All practical, effective, and safe means should be used based on risk/benefit analysis. Multiple treatments are typically used in combination, and other treatments may be more effective. Only 24% of curcumin studies show zero events with treatment. The quality of non-prescription supplements can vary widely [Crawford, Crighton].

• 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.

Covid Analysis et al., 30 Sep 2022, preprint, 1 author.

Immunomodulatory role of Nanocurcumin in COVID-19 patients with dropped natural killer cells frequency and function

Abbaspour-Aghdam et al., European Journal of Pharmacology, doi:10.1016/j.ejphar.2022.175267

RCT with 30 nanocurcumin and 30 control patients in Iran, showing lower mortality and improved recovery, without statistical significance, and improved NK cell function. 160mg nanocurcumin for 21 days.

risk of death, 71.4% lower, RR 0.29, p = 0.15, treatment 2 of 30 (6.7%), control 7 of 30 (23.3%), NNT 6.0.

risk of no recovery, 86.3% lower, RR 0.14, p = 0.04, treatment 1 of 28 (3.6%), control 6 of 23 (26.1%), NNT 4.4, dyspnea.

risk of no recovery, 89.9% lower, RR 0.10, p = 0.04, treatment 0 of 28 (0.0%), control 4 of 23 (17.4%), NNT 5.8, relative risk is not 0 because of continuity correction due to zero events, fever >39.0.

risk of no recovery, 38.4% lower, RR 0.62, p = 0.17, treatment 9 of 28 (32.1%), control 12 of 23 (52.2%), NNT 5.0, bilateral chest radiograph involvement.

risk of no recovery, 58.9% lower, RR 0.41, p = 0.27, treatment 3 of 28 (10.7%), control 6 of 23 (26.1%), NNT 6.5, cough.

risk of no recovery, 81.6% lower, RR 0.18, p = 0.20, treatment 0 of 28 (0.0%), control 2 of 23 (8.7%), NNT 12, relative risk is not 0 because of continuity correction due to zero events, headache.

Abbaspour-Aghdam et al., 17 Sep 2022, Randomized Controlled Trial, placebo-controlled, Iran, peer-reviewed, 16 authors, trial IRCT20200324046851N1.

Effect of natural products use prior to infection with COVID-19 on disease severity and hospitalization: A self-reported cross-sectional survey study

Nimer et al., F1000Research, doi:10.12688/f1000research.121933.1

Survey 2,148 COVID-19 recovered patients in Jordan, showing lower hospitalization with turmeric prophylaxis, not reaching statistical significance.

risk of hospitalization, 30.8% lower, RR 0.69, p = 0.08, treatment 29 of 329 (8.8%), control 179 of 1,819 (9.8%), adjusted, OR converted to RR, multivariable.

risk of severe case, 12.6% lower, RR 0.87, p = 0.47, treatment 40 of 329 (12.2%), control 211 of 1,819 (11.6%), adjusted, OR converted to RR, multivariable.

Nimer et al., 10 Jun 2022, retrospective, Jordan, peer-reviewed, survey, mean age 40.2, 4 authors, study period March 2021 - July 2021.

The efficacy of curcumin-piperine co-supplementation on clinical symptoms, duration, severity, and inflammatory factors in COVID-19 outpatients: a randomized double-blind, placebo-controlled trial

Askari et al., Trials, doi:10.1186/s13063-022-06375-w

Small RCT 46 outpatients in Iran, 23 treated with curcimin-piperine, showing no significant differences in recovery. 1000mg curcumin and 10mg piperine/day for 14 days.

risk of no recovery, 125.0% higher, RR 2.25, p = 0.58, treatment 3 of 8 (37.5%), control 1 of 6 (16.7%), dyspnea.

risk of no recovery, 433.3% higher, RR 5.33, p = 0.19, treatment 2 of 6 (33.3%), control 0 of 7 (0.0%), continuity correction due to zero event, ague.

risk of no recovery, 72.9% lower, RR 0.27, p = 0.04, treatment 2 of 12 (16.7%), control 8 of 13 (61.5%), NNT 2.2, weakness.

risk of no recovery, 40.0% lower, RR 0.60, p = 0.42, treatment 3 of 10 (30.0%), control 7 of 14 (50.0%), NNT 5.0, muscular pain.

risk of no recovery, 38.5% lower, RR 0.62, p = 0.65, treatment 4 of 13 (30.8%), control 4 of 8 (50.0%), NNT 5.2, headache.

risk of no recovery, 71.4% higher, RR 1.71, p = 1.00, treatment 2 of 7 (28.6%), control 1 of 6 (16.7%), sore throat.

risk of no recovery, 12.5% lower, RR 0.88, p = 1.00, treatment 1 of 8 (12.5%), control 1 of 7 (14.3%), NNT 56, sputum cough.

risk of no recovery, no change, RR 1.00, p = 1.00, treatment 3 of 13 (23.1%), control 3 of 13 (23.1%), dry cough.

Askari et al., 6 Jun 2022, Double Blind Randomized Controlled Trial, placebo-controlled, Iran, peer-reviewed, 11 authors, study period November 2020 - April 2021, trial IRCT20121216011763N46.

Effect of ArtemiC in patients with COVID-19: A Phase II prospective study

Hellou et al., Journal of Cellular and Molecular Medicine, doi:10.1111/jcmm.17337

RCT 50 hospitalized patients in Israel, 33 treated with curcumin, vitamin C, artemisinin, and frankincense oral spray, showing improved recovery with treatment.

relative NEWS2 score, 76.7% better, RR 0.23, p = 0.04, treatment mean 0.52 (±0.67) n=33, control mean 2.23 (±3.2) n=17, day 15.

risk of oxygen therapy, 92.2% lower, RR 0.08, p = 0.01, treatment 0 of 33 (0.0%), control 4 of 17 (23.5%), NNT 4.2, relative risk is not 0 because of continuity correction due to zero events, day 15.

oxygen time, 69.7% lower, relative time 0.30, p = 0.17, treatment mean 2.3 (±1.4) n=33, control mean 7.6 (±4.6) n=17.

hospitalization time, 13.3% lower, relative time 0.87, p = 0.92, treatment mean 7.8 (±7.3) n=33, control mean 9.0 (±8.0) n=17.

risk of no viral clearance, 9.8% lower, RR 0.90, p = 0.77, treatment 14 of 33 (42.4%), control 8 of 17 (47.1%), NNT 22, day 15.

Hellou et al., 19 May 2022, Double Blind Randomized Controlled Trial, placebo-controlled, Israel, peer-reviewed, 6 authors, this trial uses multiple treatments in the treatment arm (combined with vitamin C, artemisinin, and frankincense) - results of individual treatments may vary, trial NCT04382040 (history).

Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study

Nag et al., Computers in Biology and Medicine, doi:10.1016/j.compbiomed.2022.105552

In Silico study showing showing significant inhibitory potential of curcumin for omicron.

Nag et al., 1 May 2022, India, peer-reviewed, 4 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Oral Co-Supplementation of Curcumin, Quercetin, and Vitamin D3 as an Adjuvant Therapy for Mild to Moderate Symptoms of COVID-19—Results From a Pilot Open-Label, Randomized Controlled Trial

Khan et al., Frontiers in Pharmacology, doi:10.3389/fphar.2022.898062

RCT 50 COVID+ outpatients in Pakistan, 25 treated with curcumin, quercetin, and vitamin D, showing significantly faster viral clearance, significantly improved CRP, and faster resolution of acute symptoms (p=0.154). 168mg curcumin, 260mg quercetin and 360IU cholecalciferol.

risk of no recovery, 33.3% lower, RR 0.67, p = 0.15, treatment 10 of 25 (40.0%), control 15 of 25 (60.0%), NNT 5.0.

relative CRP reduction, 39.1% better, RR 0.61, p = 0.006, treatment 25, control 25.

risk of no viral clearance, 50.0% lower, RR 0.50, p = 0.009, treatment 10 of 25 (40.0%), control 20 of 25 (80.0%), NNT 2.5.

Khan et al., 1 May 2022, Randomized Controlled Trial, Pakistan, peer-reviewed, 7 authors, study period 2 September, 2021 - 28 November, 2021, this trial uses multiple treatments in the treatment arm (combined with quercetin and vitamin D) - results of individual treatments may vary, trial NCT05130671 (history).

The effect of curcumin on the risk of mortality in patients with COVID-19: A systematic review and meta-analysis of randomized trials

Kow et al., Phytotherapy Research, doi:10.1002/ptr.7468

Meta analysis of 3 curcumin RCTs showing lower mortality with treatment. Author notes the small sample sizes of the included trials.

risk of death, 77.0% lower, OR 0.23, p = 0.002, RR approximated with OR.

Kow et al., 28 Apr 2022, peer-reviewed, 3 authors.

In vitro antiviral activity against SARS-CoV-2 of common herbal medicinal extracts and their bioactive compounds

Leka et al., Phytotherapy Research, doi:10.1002/ptr.7463 (In Vitro)

In Vitro study showing antiviral activity of curcumin longa, with protection against SARS-CoV-2-induced cytopathic effects at a concentration of 3.125μg/ml.

Leka et al., 9 Apr 2022, peer-reviewed, 6 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

A Randomized, Controlled, Blinded, Parallel Group, Clinical Trial to study the role of Ayurcov (AyurCoro3), one day regimen as an adjuvant therapy for COVID-19 disease management, at dedicated Covid Hospital (DCH) in India

Sankhe et al., Complementary Therapies in Medicine, doi:10.1016/j.ctim.2022.102824

RCT with 60 hospitalized patients treated with Ayurcov and 60 control patients in India, showing improved viral clearance and faster symptom resolution in the mild/moderate group, but no significant differences in the severe group. Ayurcov contains curcuma longa, go ark, sphatika (alum), sita (rock candy), godugdham (bos indicus) milk, and goghritam (bos indicus ghee).

risk of death, 85.7% lower, RR 0.14, p = 0.24, treatment 0 of 60 (0.0%), control 3 of 60 (5.0%), NNT 20, relative risk is not 0 because of continuity correction due to zero events.

risk of mechanical ventilation, 85.7% lower, RR 0.14, p = 0.24, treatment 0 of 60 (0.0%), control 3 of 60 (5.0%), NNT 20, relative risk is not 0 because of continuity correction due to zero events.

risk of ICU admission, 66.7% lower, RR 0.33, p = 0.62, treatment 1 of 60 (1.7%), control 3 of 60 (5.0%), NNT 30.

hospitalization time, 10.0% lower, relative time 0.90, p = 0.40, treatment 45, control 45, moderate group.

hospitalization time, 16.7% lower, relative time 0.83, p = 0.20, treatment 15, control 15, severe group.

recovery time, 31.9% lower, relative time 0.68, p < 0.001, treatment 45, control 45, moderate group, fever.

recovery time, 36.1% lower, relative time 0.64, p < 0.001, treatment 45, control 45, moderate group, dyspnea.

recovery time, 4.3% lower, relative time 0.96, p = 0.74, treatment 15, control 15, severe group, fever.

recovery time, 4.8% higher, relative time 1.05, p = 0.10, treatment 15, control 15, severe group, dyspnea.

relative Ct increase, 44.4% better, RR 0.56, p = 0.003, treatment mean 9.98 (±6.39) n=44, control mean 5.55 (±6.91) n=43, moderate group.

Sankhe et al., 25 Mar 2022, Single Blind Randomized Controlled Trial, India, peer-reviewed, 10 authors, this trial uses multiple treatments in the treatment arm (combined with gomutra, potassium alum, khadisakhar, bos indicus milk, ghee) - results of individual treatments may vary.

A Randomised, Double-Blind, Placebo-Controlled Trial Evaluating Concentrated Phytochemical-Rich Nutritional Capsule in Addition to a Probiotic Capsule on Clinical Outcomes among Individuals with COVID-19—The UK Phyto-V Study

Thomas et al., COVID, doi:10.3390/covid2040031

RCT 147 long COVID patients in the UK, 56 treated with a phytochemical-rich concentrated food capsule, showing improved recovery with treatment. Treatment included curcumin, bioflavonoids, chamomile, ellagic acid, and resveratrol.

relative improvement, 44.3% better, RR 0.56, p = 0.02, treatment mean 6.1 (±7.5) n=74, control mean 3.4 (±6.1) n=73, CFS.

relative improvement, 81.8% better, RR 0.18, p < 0.001, treatment mean 6.6 (±10.5) n=74, control mean 1.2 (±7.4) n=73, SWS.

relative improvement, 63.6% better, RR 0.36, p = 0.02, treatment mean 1.1 (±2.0) n=74, control mean 0.4 (±1.5) n=73, CSS.

Thomas et al., 22 Mar 2022, Double Blind Randomized Controlled Trial, placebo-controlled, United Kingdom, peer-reviewed, 7 authors, study period May 2020 - May 2021, this trial uses multiple treatments in the treatment arm (combined with bioflavonoids, chamomile, ellagic acid, resveratrol) - results of individual treatments may vary, Phyto-V trial.

Immune-boosting effect of natural remedies and supplements on progress of, and recovery from COVID-19 infection

Shehab et al., Tropical Journal of Pharmaceutical Research, doi:10.4314/tjpr.v21i2.13

Retrospective survey-based analysis of 349 COVID-19 patients, showing a lower risk of severe cases with vitamin D, zinc, turmeric, and honey prophylaxis in unadjusted analysis, without statistical significance. REC/UG/2020/03.

risk of severe case, 42.4% lower, RR 0.58, p = 0.55, treatment 2 of 32 (6.2%), control 24 of 221 (10.9%), NNT 22, unadjusted, severe vs. mild cases.

Excluded in after exclusion results of meta analysis: unadjusted results with no group details.

Shehab et al., 28 Feb 2022, retrospective, multiple countries, peer-reviewed, survey, 7 authors, study period September 2020 - March 2021.

The Effect of Curcumin and Virgin Coconut Oil Towards Cytokines Levels in COVID-19 Patients at Universitas Sebelas Maret Hospital, Surakarta, Indonesia

Hartono et al., Pharmacognosy Journal, doi:10.5530/pj.2022.14.27

RCT with 30 patients treated with curcumin and virgin coconut oil (VCO), and 30 SOC patients in Indonesia, showing faster viral clearance with treatment. Treatment also reduced IL-1β, IL-2, IL-6, IL-18, and IFN-β levels. VCO improves the bioavailability of curcumin. There were large unadjusted differences in baseline severity and age, for example 20% vs. 47% of patients >50. VCO 30ml and curcumin 1g tid for 21 days. 066/UN27.06.6.1/KEPK/EC/2020.

risk of no viral clearance, 53.3% lower, RR 0.47, p < 0.001, treatment 14 of 30 (46.7%), control 30 of 30 (100.0%), NNT 1.9, day 10.

risk of no viral clearance, 75.0% lower, RR 0.25, p = 0.002, treatment 4 of 30 (13.3%), control 16 of 30 (53.3%), NNT 2.5, day 14.

risk of no viral clearance, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 30 (0.0%), control 1 of 30 (3.3%), NNT 30, relative risk is not 0 because of continuity correction due to zero events, day 21.

Excluded in after exclusion results of meta analysis: randomization resulted in significant baseline differences that were not adjusted for.

Hartono et al., 22 Feb 2022, Randomized Controlled Trial, Indonesia, peer-reviewed, 13 authors, this trial uses multiple treatments in the treatment arm (combined with virgin coconut oil) - results of individual treatments may vary.

Molecular Docking and Molecular Dynamics Simulations Discover Curcumin Analogue as a Plausible Dual Inhibitor for SARS-CoV-2

Rampogu et al., International Journal of Molecular Sciences, doi:10.3390/ijms23031771

In Silico molecular dynamics simulation study finding a curcumin analogue (curA) as a promising dual inhibitor for SARS-CoV-2.

Rampogu et al., 4 Feb 2022, peer-reviewed, 5 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Curcumin as adjuvant Therapy in Mild - Moderate Covid 19

Kartika et al., ICE on IMERI, 2021 (Preprint)

Retrospective 246 hospitalized patients in Indonesia, 136 treated with curcumin, showing shorter hospitalization time with treatment. All patients received vitamin C, D, and zinc.

hospitalization time, 41.0% lower, relative time 0.59, p = 0.048, treatment 139, control 107.

Kartika et al., 28 Jan 2022, retrospective, Indonesia, preprint, 6 authors, study period January 2021 - June 2021.

Inhibitory effects of specific combination of natural compounds against SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants

Goc et al., European Journal of Microbiology and Immunology, doi:10.1556/1886.2021.00022 (In Vitro)

In Vitro study testing combinations of plant extracts and micronutrients with several variants of SARS-CoV-2. A combination of vitamin C, N-acetylcysteine, curcumin, quercetin, resveratrol, theaflavin, naringenin, baicalin, and broccoli extract showed the highest inhibition of RBD binding, and also decreased RdRp, furin, and cathepsin L activity.

Goc et al., 21 Jan 2022, peer-reviewed, 5 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Antiinflammatory potential of nano-curcumin as an alternative therapeutic agent for the treatment of mild-to-moderate hospitalized COVID-19 patients in a placebo-controlled clinical trial

Asadirad et al., Phytotherapy Research, doi:10.1002/ptr.7375

RCT 60 hospitalized patients in Iran, 30 treated with nano-curcumin, showing significant improvements in inflammatory cytokines, and improvements in clinical outcomes without statistical significance. 240 mg/day nano-curcumin for 7 days.

risk of death, 25.9% lower, RR 0.74, p = 0.74, treatment 5 of 27 (18.5%), control 6 of 24 (25.0%), NNT 15, excluding patients that stopped treatment due to progression - 3 for curcumin and 6 for control.

risk of progression, 50.0% lower, RR 0.50, p = 0.47, treatment 3 of 30 (10.0%), control 6 of 30 (20.0%), NNT 10.0.

risk of unresolved fever, 45.3% lower, RR 0.55, p = 0.09, treatment 8 of 27 (29.6%), control 13 of 24 (54.2%), NNT 4.1.

risk of unresolved dyspnea, 28.9% lower, RR 0.71, p = 0.72, treatment 4 of 27 (14.8%), control 5 of 24 (20.8%), NNT 17.

risk of unresolved cough, 40.7% lower, RR 0.59, p = 0.36, treatment 6 of 27 (22.2%), control 9 of 24 (37.5%), NNT 6.5.

risk of O2 <92%, 36.5% lower, RR 0.63, p = 0.51, treatment 5 of 27 (18.5%), control 7 of 24 (29.2%), NNT 9.4.

risk of O2 <97%, 20.0% lower, RR 0.80, p = 0.21, treatment 18 of 27 (66.7%), control 20 of 24 (83.3%), NNT 6.0.

Asadirad et al., 17 Jan 2022, Randomized Controlled Trial, placebo-controlled, Iran, peer-reviewed, 7 authors.

Effect of nanocurcumin supplementation on the severity of symptoms and length of hospital stay in patients with COVID-19: A randomized double-blind placebo-controlled trial

Honarkar Shafie et al., Phytotherapy Research, doi:10.1002/ptr.7374

RCT 48 hospitalized patients in Iran, 24 treated with nanocurcumin, showing lower hospitalization time with treatment. The number of patients shown in Table 3 (31 and 27 for each arm) is inconsistent with the number reported as randomized to each arm (24). 160 mg/day nanocurcumin for 6 days. IRCT20131125015536N13.

hospitalization time, 28.9% lower, relative time 0.71, p = 0.22, treatment mean 6.31 (±5.26) n=23, control mean 8.87 (±8.12) n=21.

relative pulmonary involvement score, 9.1% better, RR 0.91, treatment 23, control 21.

Excluded in meta analysis: unresolved data inconsistency.

Honarkar Shafie et al., 12 Jan 2022, Double Blind Randomized Controlled Trial, placebo-controlled, Iran, peer-reviewed, 10 authors.

Effectiveness of Curcumin on Outcomes of Hospitalized COVID-19 Patients: A Systematic Review of Clinical Trials

Vahedian-Azimi et al., Nutrients, doi:10.3390/nu14020256

Review of 6 COVID-19 curcumin studies showing that treatment resulted in significant improvement in symptoms, duration of hospitalization, and mortality, and a significant decrease in proinflammatory cytokines and increase in anti-inflammatory cytokines.

Vahedian-Azimi et al., 7 Jan 2022, peer-reviewed, 9 authors.

An integrative approach to clinical recovery for COVID-19 patients using an Ayurvedic formulation: A multicentric double-blind randomized control trial.

Bhardwaja et al., Research Square, doi:10.21203/rs.3.rs-1165680/v1 (Preprint)

Small RCT with 39 patients treated with NOQ19 and 37 placebo patients, showing improved recovery, without statistical significance. NOQ19 has multiple ingredients including curcumin and antiandrogen glycyrrhiza glabra. CTRI/2021/05/033790.

risk of no hospital discharge, 36.8% lower, RR 0.63, p = 0.67, treatment 2 of 39 (5.1%), control 3 of 37 (8.1%), NNT 34, day 7.

risk of no recovery, 89.1% lower, RR 0.11, p = 0.05, treatment 0 of 39 (0.0%), control 4 of 37 (10.8%), NNT 9.2, relative risk is not 0 because of continuity correction due to zero events, oxygen supplementation, day 5.

risk of no recovery, 80.4% lower, RR 0.20, p = 0.23, treatment 0 of 39 (0.0%), control 2 of 37 (5.4%), NNT 18, relative risk is not 0 because of continuity correction due to zero events, day 7, dsypnea.

risk of no recovery, 2.8% higher, RR 1.03, p = 1.00, treatment 13 of 39 (33.3%), control 12 of 37 (32.4%), day 7, fever.

risk of no viral clearance, 24.1% lower, RR 0.76, p = 0.47, treatment 12 of 39 (30.8%), control 15 of 37 (40.5%), NNT 10, day 7.

risk of no viral clearance, 5.1% lower, RR 0.95, p = 1.00, treatment 19 of 39 (48.7%), control 19 of 37 (51.4%), NNT 38, day 5.

risk of no viral clearance, 12.4% lower, RR 0.88, p = 0.47, treatment 24 of 39 (61.5%), control 26 of 37 (70.3%), NNT 11, day 3.

Excluded in meta analysis: combined treatments may contribute more to the effect seen.

Bhardwaja et al., 27 Dec 2021, Double Blind Randomized Controlled Trial, India, preprint, 26 authors, this trial uses multiple treatments in the treatment arm (combined with 18 other ingredients) - results of individual treatments may vary.

Curcumin Inhibits In Vitro SARS-CoV-2 Infection In Vero E6 Cells through Multiple Antiviral Mechanisms

Marín-Palma et al., Molecules, doi:10.3390/molecules26226900 (In Vitro)

In Vitro study showing antiviral and anti-inflammatory effects of curcumin during SARS-CoV-2 infection. Inhibition was seen with Vero E6 cells pre-infection and post-infection, and with D614G and the delta variant. The anti-inflammatory effect was shown with peripheral blood mononuclear cells.

Marín-Palma et al., 16 Nov 2021, peer-reviewed, 9 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols

Bahun et al., Food Chemistry, doi:10.1016/j.foodchem.2021.131594 (In Vitro)

In Silico and In Vitro study of plant polyphenols identifying quercetin, curcumin, ellagic acid, epigallocatechin gallate and resveratrol as SARS-CoV-2 3CL^pro inhibitors with IC₅₀ between 11.8µM and 23.4µM. Real-time binding was analyzed with surface plasmon resonance spectroscopy.

Bahun et al., 14 Nov 2021, peer-reviewed, 10 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Potential of turmeric-derived compounds against RNA‐dependent RNA polymerase of SARS‐CoV‐2: An in-silico approach

Singh et al., Computers in Biology and Medicine, doi:https://www.sciencedirect.com/science/article/pii/S0010482521007599

In Silico study showing strong binding affinity of curcumin and diacetylcurcumin with SARS-CoV-2 RNA‐dependent RNA polymerase. Comparison with remdesivir and favipiravir suggested greater potential of these compounds as an RdRp inhibitor.

Singh et al., 22 Oct 2021, peer-reviewed, 3 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of a Nutritional Supplement (ImmuActive) for COVID-19 Patients

Majeed et al., Evidence-Based Complementary and Alternative Medicine, doi:10.1155/2021/8447545

RCT 100 patients in India, 50 treated with ImmuActive (curcumin, andrographolides, resveratrol, zinc, selenium, and piperine), showing improved recovery with treatment.

risk of mechanical ventilation, 66.2% lower, RR 0.34, p = 1.00, treatment 0 of 45 (0.0%), control 1 of 47 (2.1%), NNT 47, relative risk is not 0 because of continuity correction due to zero events.

risk of hospitalization, 79.7% lower, RR 0.20, p = 0.49, treatment 0 of 45 (0.0%), control 2 of 47 (4.3%), NNT 24, relative risk is not 0 because of continuity correction due to zero events.

relative ordinal scale, 43.0% better, RR 0.57, p = 0.004, treatment 45, control 47, day 28.

relative time to improve one unit on ordinal scale, 30.1% lower, relative time 0.70, treatment 45, control 47.

risk of no recovery, 24.6% lower, RR 0.75, p = 0.08, treatment 26 of 45 (57.8%), control 36 of 47 (76.6%), NNT 5.3, day 28.

time to viral-, 5.8% lower, relative time 0.94, p = 0.47, treatment 45, control 47.

Majeed et al., 11 Oct 2021, Double Blind Randomized Controlled Trial, India, peer-reviewed, 4 authors, this trial uses multiple treatments in the treatment arm (combined with andrographolides, resveratrol, zinc, selenium, and piperine) - results of individual treatments may vary.

Turmeric Root and Its Bioactive Ingredient Curcumin Effectively Neutralize SARS-CoV-2 In Vitro

Bormann et al., Viruses, doi:10.3390/v13101914 (In Vitro)

In Vitro study showing curcumin neutralizes SARS-CoV2 in vitro with low subtoxic concentrations. Authors note that the clinical use of curcumin is hindered by poor bioavailability, and recommend using methods to increase bioavailability such as nanoparticles, liposomes, micelles, or adjuvants (e.g., piperine).

Bormann et al., 23 Sep 2021, peer-reviewed, 18 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

A triple-blind, placebo-controlled, randomized clinical trial to evaluate the effect of curcumin-containing nanomicelles on cellular immune responses subtypes and clinical outcome in COVID-19 patients

Hassaniazad et al., Phytotherapy Research, doi:10.1002/ptr.7294

Small RCT with 40 low risk patients in Iran, 20 treated with nano-curcumin, showing no significant difference in outcomes with treatment. Authors note that treatment can improve peripheral blood inflammatory indices and modulate immune response by decreasing Th1 and Th17 responses, increasing T regulatory responses, further reducing IL-17 and IFN-γ, and increasing suppressive cytokines TGF-β and IL-4.

relative improvement in SpO₂, 45.7% worse, RR 1.46, p = 0.90, treatment 20, control 20.

Hassaniazad et al., 19 Sep 2021, Double Blind Randomized Controlled Trial, placebo-controlled, Iran, peer-reviewed, 12 authors.

Turmeric as a Possible Treatment for COVID-19-Induced Anosmia and Ageusia

Chabot et al., Cureus, doi:10.7759/cureus.17829

Small case study of 2 patients, showing significant improvement in taste and smell shortly after one dose of a turmeric supplement. Authors note that the risk of one dose is low in healthy individuals not on medications metabolized by cytochromes P450, and the potential benefit is high.

Chabot et al., 8 Sep 2021, peer-reviewed, 2 authors.

A prospective, multi center, single blind, randomized controlled study evaluating “AyurCoro3” as an adjuvant in the treatment of mild to moderate COVID

Sankhe et al., Journal of Ayurveda and Integrated Medical Sciences, doi:10.21760/jaims.6.4.6

RCT 174 patients in India, 87 treated with AyurCoro-3 (turmeric, gomutra, potassium alum, khadisakhar, bos indicus milk, ghee), showing faster recovery with treatment. EC/NEW/INST/2019/245.

risk of death, 88.9% lower, RR 0.11, p = 0.12, treatment 0 of 87 (0.0%), control 4 of 87 (4.6%), NNT 22, relative risk is not 0 because of continuity correction due to zero events.

risk of mechanical ventilation, 75.0% lower, RR 0.25, p = 0.37, treatment 1 of 87 (1.1%), control 4 of 87 (4.6%), NNT 29.

risk of no 2-point improvement, 46.5% lower, RR 0.54, p = 0.002, treatment 29 of 87 (33.3%), control 60 of 87 (69.0%), NNT 2.8, inverted to make RR<1 favor treatment, OR converted to RR, day 7 mid-recovery.

hospitalization time, 10.0% lower, relative time 0.90, p = 0.40, treatment 87, control 87.

Sankhe et al., 10 Aug 2021, Randomized Controlled Trial, India, peer-reviewed, 8 authors, this trial uses multiple treatments in the treatment arm (combined with gomutra, potassium alum, khadisakhar, bos indicus milk, ghee) - results of individual treatments may vary.

The enhanced bioavailability of free curcumin and bioactive-metabolite tetrahydrocurcumin from a dispersible, oleoresin-based turmeric formulation

Panda et al., Medicine, doi:10.1097/MD.0000000000026601

Bioavailability RCT comparing CURCUGEN, a 50% curcuminoids-concentrated turmeric extract, with curcuminoids 95% standardized extract (C-95), showing significant improvements in bioavailability.

Panda et al., 9 Jul 2021, peer-reviewed, 4 authors.

Potential In Vitro Inhibition of Selected Plant Extracts against SARS-CoV-2 Chymotripsin-Like Protease (3CLPro) Activity

Guijarro-Real et al., Foods, doi:10.3390/foods10071503 (In Vitro)

In Vitro study of several plant extracts, showing strong inhibition of SARS-CoV-2 3CL^pro activity by turmeric rhizomes. Commercial curcumin also inhibited 3CL^pro activity, but did not fully account for the inhibitory effect of turmeric rhizomes extracts, suggesting that other components of the turmeric extract also play a main role in inhibiting 3CL^pro activity.

Guijarro-Real et al., 29 Jun 2021, peer-reviewed, 5 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Oral nano-curcumin formulation efficacy in the management of mild to moderate outpatient COVID-19: A randomized triple-blind placebo-controlled clinical trial

Ahmadi et al., Food Science and Nutrition, doi:10.1002/fsn3.2226

RCT 60 outpatients in Iran, 30 treated with nano-curcumin showing lower hospitalization and faster recovery with treatment.

risk of hospitalization, 85.7% lower, RR 0.14, p = 0.24, treatment 0 of 30 (0.0%), control 3 of 30 (10.0%), NNT 10.0, relative risk is not 0 because of continuity correction due to zero events.

recovery time, 20.6% lower, relative time 0.79, p = 0.37, treatment 30, control 30.

Ahmadi et al., 19 Jun 2021, Double Blind Randomized Controlled Trial, Iran, peer-reviewed, 11 authors.

Phenolic compounds disrupt spike-mediated receptor-binding and entry of SARS-CoV-2 pseudo-virions

Goc et al., PLOS ONE, doi:10.1371/journal.pone.0253489 (In Vitro)

In Vitro study of 56 polyphenols showing that curcumin has high binding affinity to the RBD of the SARS-CoV-2 spike protein, inhibits ACE2 at non-toxic concentrations, and decreases activity of TMPRSS2. Promising results were also seen for brazilin and theaflavin-3,3’-digallate.

Goc et al., 17 Jun 2021, peer-reviewed, 4 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Bioactive Polyphenolic Compounds Showing Strong Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus 2

Kandeil et al., Pathogens, doi:10.3390/pathogens10060758 (In Vitro)

Vero E6 In Vitro study showing curcumin, hesperidin, and quercetin significantly inhibited SARS-CoV-2 replication, and In Silico analysis with promising M^pro and spike docking results.

Kandeil et al., 15 Jun 2021, peer-reviewed, 11 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Oral Curcumin With Piperine as Adjuvant Therapy for the Treatment of COVID-19: A Randomized Clinical Trial

Pawar et al., Frontiers in Pharmacology, doi:10.3389/fphar.2021.669362

RCT 140 patients, 70 treated with curcumin and piperine (for absorption), showing faster recovery, lower progression, and lower mortality with treatment. Control group partients also received probiotics. CTRI/2020/05/025482.

risk of death, 81.8% lower, RR 0.18, p = 0.02, treatment 2 of 70 (2.9%), control 11 of 70 (15.7%), NNT 7.8.

risk of death, 60.0% lower, RR 0.40, p = 0.39, treatment 2 of 15 (13.3%), control 5 of 15 (33.3%), NNT 5.0, severe group.

risk of death, 90.9% lower, RR 0.09, p = 0.05, treatment 0 of 25 (0.0%), control 5 of 25 (20.0%), NNT 5.0, relative risk is not 0 because of continuity correction due to zero events, moderate group.

risk of death, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 30 (0.0%), control 1 of 30 (3.3%), NNT 30, relative risk is not 0 because of continuity correction due to zero events, mild group.

Pawar et al., 28 May 2021, Double Blind Randomized Controlled Trial, India, peer-reviewed, 8 authors.

Patients’ Behavior Regarding Dietary or Herbal Supplements before and during COVID-19 in Saudi Arabia

Aldwihi et al., International Journal of Environmental Research and Public Health, doi:10.3390/ijerph18105086

Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.

risk of hospitalization, 31.2% lower, RR 0.69, p = 0.10, treatment 30 of 144 (20.8%), control 207 of 594 (34.8%), NNT 7.1, adjusted, OR converted to RR, multivariable.

Aldwihi et al., 11 May 2021, retrospective, Saudi Arabia, peer-reviewed, survey, mean age 36.5, 8 authors, study period August 2020 - October 2020.

Curcumin as a Potential Treatment for COVID-19

Rattis et al., Frontiers in Pharmacology, doi:10.3389/fphar.2021.675287 (Review)

Review of curcumin for COVID-19 including potential antiviral, anti-inflammatory, anticoagulant, antiplatelet, and cytoprotective effects.

Rattis et al., 7 May 2021, peer-reviewed, 3 authors.

Nanocurcumin improves Treg cell responses in patients with mild and severe SARS-CoV2

Tahmasebi et al., Life Sciences, doi:10.1016/j.lfs.2021.119437

RCT 40 hospitalized, 40 ICU, and 40 control patients in Iran, showing lower mortality and improved regulatory T cell responses with nanocurcumin treatment (SinaCurcumin).

risk of death, 83.3% lower, RR 0.17, p = 0.11, treatment 1 of 40 (2.5%), control 6 of 40 (15.0%), NNT 8.0.

risk of death, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 20 (0.0%), control 1 of 20 (5.0%), NNT 20, relative risk is not 0 because of continuity correction due to zero events, non-ICU patients.

risk of death, 80.0% lower, RR 0.20, p = 0.18, treatment 1 of 20 (5.0%), control 5 of 20 (25.0%), NNT 5.0, ICU patients.

Tahmasebi et al., 28 Mar 2021, Double Blind Randomized Controlled Trial, Iran, peer-reviewed, 14 authors.

Oral nano-curcumin formulation efficacy in management of mild to moderate hospitalized coronavirus disease-19 patients: An open label nonrandomized clinical trial

Saber-Moghaddam et al., Phytotherapy Research, doi:10.1002/ptr.7004

Small prospective nonrandomized trial with 41 patients, 21 treated with curcumin, showing lower disease progression and faster recovery with treatment. IRCT20200408046990N1.

risk of progression, 94.3% lower, RR 0.06, p = 0.001, treatment 0 of 21 (0.0%), control 8 of 20 (40.0%), NNT 2.5, relative risk is not 0 because of continuity correction due to zero events.

risk of no recovery, 38.4% lower, RR 0.62, p = 0.04, treatment 11 of 21 (52.4%), control 17 of 20 (85.0%), NNT 3.1.

hospitalization time, 44.8% lower, relative time 0.55, p < 0.001, treatment 21, control 20.

Saber-Moghaddam et al., 3 Jan 2021, prospective, Iran, peer-reviewed, 9 authors.

A Randomized, Comparative Clinical Study to Evaluate the Activity of CurvicTM Formulation for Management of SARS-COV-2 Infection (COVID-19)

Dound et al., Journal of Clinical Trials, S3:004

RCT 200 COVID-19 positive patients in India, 100 treated with Curcumin, Vitamin C, Vitamin K2-7, and L-Selenomethionine, showing faster recovery with treatment.

relative improvement on 6-point scale, 33.3% better, RR 0.67, p < 0.001, treatment 100, control 100.

Excluded in after exclusion results of meta analysis: potential randomization failure.

Dound et al., 16 Nov 2020, Randomized Controlled Trial, India, peer-reviewed, 5 authors, this trial uses multiple treatments in the treatment arm (combined with vitamin C, vitamin K2-7, and l-selenomethionine) - results of individual treatments may vary.

The combination of bromelain and curcumin as an immune-boosting nutraceutical in the prevention of severe COVID-19

Kritis et al., Metabolism Open, doi:10.1016/j.metop.2020.100066 (Review)

Review of the potential benefits of bromelain and curcumin for COVID-19, and potential synergistic effects of the combination.

Kritis et al., 13 Nov 2020, peer-reviewed, 4 authors.

Nano-curcumin therapy, a promising method in modulating inflammatory cytokines in COVID-19 patients

Valizadeh et al., Int. Immunopharmacol., doi:10.1016/j.intimp.2020.107088

Small RCT with 40 nano-curcumin patients and 40 control patients showing lower mortality with treatment. Authors conclude that nano-curcumin may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may improve clinical outcomes.

risk of death, 50.0% lower, RR 0.50, p = 0.30, treatment 4 of 20 (20.0%), control 8 of 20 (40.0%), NNT 5.0.

Valizadeh et al., 20 Oct 2020, Double Blind Randomized Controlled Trial, Iran, peer-reviewed, 12 authors.

COVID-19 and heme oxygenase: novel insight into the disease and potential therapies

Hooper, P., Cell Stress and Chaperones, doi:10.1007/s12192-020-01126-9 (Theory)

Proposal that COVID-19 risk is related to low intracellular heme oxygenase (HO-1), and that therapies that raise HO-1 may be beneficial, which includes fluvoxamine, certain anesthetics (sevoflurane or isoflurane), hemin, estrogen, statins, curcumin, resveratrol, and melatonin. Authors note that cigarette smoke is associated with increased HO-1 in lung fibroblasts and vascular endothelial cells, which may help explain the lower risk for smokers seen in several studies.

Hooper et al., 4 Jun 2020, peer-reviewed, 1 author.

In-Silico Identification of Potent Inhibitors of COVID-19 Main Protease (Mpro) and Angiotensin Converting Enzyme 2 (ACE2) from Natural Products: Quercetin, Hispidulin, and Cirsimaritin Exhibited Better Potential Inhibition than Hydroxy-Chloroquine Against COVID-19 Main Protease Active Site and ACE2

Sekiou et al., ChemRxiv, doi:10.26434/chemrxiv.12181404.v1 (Preprint)

In Silico study of natural compounds identifying quercetin, curcumin, hispidulin, cirsimaritin, sulfasalazine, and artemisin as potential compounds that inhibit SARS-CoV-2.

Sekiou et al., 24 Apr 2020, preprint, 4 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.