Indian Randomized Controlled Trial Shows Positive Results for Natural Supplements Targeting COVID-19

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In another positive data point for natural supplements in the fight against COVID-19, yet again, researchers, this time in India, reveal that natural substances could be as if not more efficacious as what big pharmaceutical companies spend hundreds of millions of dollars in investments to test on the market. In this case, a component of Turmeric (Curcumin) and Piperine (black pepper) showed impressive results in a double-blind, randomized control trial.

TrialSite Community member, Paul Elkins, submitted this study summary, which was reviewed by the TrialSite team.

The Study

In this RCT they tracked many important clinical markers of disease progression in Covid-19, symptom resolution, and progression to serious outcomes. They also used subgroup analysis to separate the effects in Mild, Moderate and Severe disease. Many of the well-funded Big Pharma trials should take note of this design in order to elucidate a therapeutics efficacy in specific target subjects.  It’s well known that Covid-19 is a disease of two stages. The early viral infection stage and the later pulmonary phase driven by hyperinflammation, coagulation and immune dysregulation.  It’s critical to ascertain which of these phases a therapeutics’ Mechanism Of Action (MOA) targets and to measure the results in the target group. One limitation of this study is that the number of subjects is relatively small but that’s typical in a study not funded by Big Pharma looking to capitalize on a lucrative therapeutic. 

They call the treatment group C3 and the control group Non-C3.  Due to the multiple endpoints the results are a bit complex to sort through. In general, they showed statistically significant improvement in many clinical markers and symptoms. They also showed a reduction in deaths (1 in the C3 group and 5 in the control group). 

The Results

“in the mild, moderate, and severe subgroups, compared to the patients of the non-C3 group, patients of the C3 group showed early symptomatic recovery (of fever, cough, sore throat, breathlessness), less deterioration over the period of hospital stay, lower incidence of red flag signs, and better ability to maintain oxygen saturation above 94% on room air throughout the hospital stay. Further, patients of the C3 group could maintain SpO2 above 94% on room air for more days, and fewer patients of the C3 group required oxygen therapy with or without HFNO, failed to maintain SpO2 >88% despite oxygenation, or required intubation and mechanical ventilation to maintain SpO2 above 88%. Although deterioration in laboratory parameters was observed in patients from both groups, the rise in D-Dimer levels was less severe in the C3 Group than in the non-C3 group.

The Neutrophil/lymphocyte ratio was >3.5 in both groups, and differences between the moderate and severe subgroups were not significant. 3/30 patients from the mild C3 subgroup and 7/30 from the non-C3 subgroup showed the development of pneumonitis on chest X-rays during hospitalization. All patients in the moderate and severe subgroups of the C3 and non-C3 groups presented with bilateral pneumonitis, except one patient in the moderate C3 subgroup, who had unilateral pneumonitis.

Fewer patients in the study group required the administration of the COVID awakening protocol, remdesivir, low molecular weight heparin, or unfractionated heparin in addition to oral doxycycline, favipiravir, steroids, and nutritional supplements. None of the patients in the moderate C3 subgroup required tocilizumab injections, while 5/25 patients in the Moderate Non-C3 subgroup did. 2/15 patients from the severe C3 subgroup and 4/15 from the severe Non-C3 subgroup required and received tocilizumab per protocol. Unfortunately, none of these patients survived.

Secondary Outcomes

As shown in , the duration of hospitalization was almost the same in the C3 and non-C3 mild subgroups; however, it was significantly lower in the moderate and severe C3 subgroups than in the corresponding non-C3 subgroups. Fewer patients required mechanical ventilator support and suffered thromboembolic episodes in the C3 group than in the non-C3 group. Oral aspirin was not given to any of these patients.

There were no deaths in the mild and moderate C3 subgroups, while there was 1 death out of 30 in the mild non-C3 subgroup and 5 deaths out of 25 in the moderate non-C3 subgroup. There were fewer deaths (2/15) in the severe C3 subgroup than in the severe non-C3 subgroup (5/15).”

 Lead Research/Investigator

Kirti S. Pawar, Giriraj Hospital and Intensive Care unit, Baramati, India

Other authors can be reviewed here


  1. I didn’t notice the link to the paper, so here it is:
    “Oral Curcumin With Piperine as Adjuvant Therapy for the Treatment of COVID-19: A Randomized Clinical Trial”

    Control arm patients were given twice daily probiotics to enhance their gut biome. Study group got 525mg curcumin/2.5mg piperine twice a day. The typical curcumin/piperine supplement sold in the USA has this amount of the supplements, although many of them are about double this strength.

    A healthy gut biome supports the immune system. Both arms of this trial could have benefited from probiotics.

    Bioperine is a trade name for a slightly modified version of piperine. Both help boost the bioavailability of curcumin by orders of magnitude. Piperine also helps coenzyme CoQ10.

    Curcumin and piperine have been part of traditional Indian medicine for a very long time. Both are well known to reduce the swelling associated with arthritis. Frankincense, aka boswellia, is also on the list of arthritis supplements, along with Glucosamine/Chondroitin/MSM. I read somewhere some time ago that the latter may also have some benefit against this virus. None of this surprises me; anything you can do to reduce inflammation and/or thin mucus ought to be helpful here. I’d put N-AC on the menu as well, now that studies have shown it has several benefits against the virus. Coincidentally, I hear the FDA is trying to ban NAC.

    1. Thank you for this information. Prior to my first Covid symptoms on 3/6/2020, I was already taking Curcumine + piperine for other medical issues, along with most of the other supplements and vitamins (D3, C, B vitamins, quercetin, omega 3) on the recommended long Covid protocols. As sick as I was back then, I can’t help wondering if it would have been worse (e.g. might the breathing difficulty have indeed grown just a hair worse and forced me to go to the ER for help, a terrifying question I deliberated every night for about a month), had I not been on all these supplements? As-is, I am going into my 16th month with long Covid, finally with ivermectin added to the regimen. There are signs of improvement. Hopefully this is the start of recovery.

      1. Ask your doc for Fluvoxamine, 50mg twice a day for 2 weeks, to go along with the IVM. Combined, both have shown good results in several forms of the Long Haul symptoms. Info is online.