Curcumin for COVID-19: real-time analysis of all 18 studies

Curcumin for COVID-19: real-time meta analysis of 9 studies

Covid Analysis (Preprint) (meta analysis)

• Statistically significant improvements are seen for mortality, progression, and recovery. 5 studies from 5 independent teams in 2 different countries show statistically significant improvements in isolation (3 for the most serious outcome).

• Meta analysis using the most serious outcome reported shows 59% [30‑76%] improvement. Results are slightly worse for Randomized Controlled Trials.

• Currently there is limited data, with a total of only 41 control events for the most serious outcome in trials to date.

• 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 44% of curcumin studies show zero events in the treatment arm.

• Multiple treatments are typically used in combination, and other treatments may be more effective.

• Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all variants. All practical, effective, and safe means should be used, including treatments, as supported by Pfizer [Pfizer]. Denying the efficacy of treatments increases the risk of COVID-19 becoming endemic; and increases mortality, morbidity, and collateral damage.

• All data to reproduce this paper and sources are in the appendix.

	Studies	Early treatment	Late treatment	Patients	Authors
All studies	9	71% [26‑89%]	58% [-3‑83%]	867	83
RCTs	8	60% [12‑82%]	58% [-3‑83%]	826	74
Percentage improvement with curcumin treatment

Covid Analysis et al., 1/5/2022, preprint, 1 author.

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 (Peer Reviewed) (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., 11/16/2021, 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 (Peer Reviewed) (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., 11/14/2021, 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 (Peer Reviewed)

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., 10/22/2021, 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 (Peer Reviewed)

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., 10/11/2021, Double Blind Randomized Controlled Trial, India, South Asia, 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 (Peer Reviewed) (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., 9/23/2021, 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 (Peer Reviewed)

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., 9/19/2021, Double Blind Randomized Controlled Trial, Iran, Middle East, 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 (Peer Reviewed)

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., 9/8/2021, 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 (Peer Reviewed)

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, 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., 8/10/2021, Randomized Controlled Trial, India, South Asia, 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 (Peer Reviewed)

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., 7/9/2021, 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 (Peer Reviewed) (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., 6/29/2021, 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 (Peer Reviewed)

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., 6/19/2021, Double Blind Randomized Controlled Trial, Iran, Middle East, 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 (Peer Reviewed) (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., 6/17/2021, peer-reviewed, 4 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 (Peer Reviewed)

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., 5/28/2021, Double Blind Randomized Controlled Trial, India, South Asia, peer-reviewed, 8 authors.

Curcumin as a Potential Treatment for COVID-19

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

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

Rattis et al., 5/7/2021, 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 (Peer Reviewed)

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., 3/28/2021, Double Blind Randomized Controlled Trial, Iran, Middle East, 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 (Peer Reviewed)

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., 1/3/2021, prospective, Iran, Middle East, 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 (Peer Reviewed)

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.

Dound et al., 11/16/2020, Randomized Controlled Trial, India, South Asia, 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) (Peer Reviewed)

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

Kritis et al., 11/13/2020, 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 (Peer Reviewed)

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., 10/20/2020, Double Blind Randomized Controlled Trial, Iran, Middle East, 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 (Peer Reviewed) (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., 6/4/2020, 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., 4/24/2020, preprint, 4 authors.

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

Antiandrogens	(meta)	Metformin	(meta)
Aspirin	(meta)	Molnupiravir	(meta)
Bamlanivimab	(meta)	Nigella Sativa	(meta)
Bromhexine	(meta)	Nitazoxanide	(meta)
Budesonide	(meta)	Paxlovid	(meta)
Casirivimab/i..	(meta)	Povidone-Iod..	(meta)
Colchicine	(meta)	Probiotics	(meta)
Conv. Plasma	(meta)	Proxalutamide	(meta)
Curcumin	(meta)	Quercetin	(meta)
Favipiravir	(meta)	Remdesivir	(meta)
Fluvoxamine	(meta)	Sotrovimab	(meta)
Hydroxychlor..	(meta)	Vitamin A	(meta)
Iota-carragee..	(meta)	Vitamin C	(meta)
Ivermectin	(meta)	Vitamin D	(meta)
Melatonin	(meta)	Zinc	(meta)

Other Treatments		Global Adoption