Time to bring scientific rigour to the complex challenge of Ayurvedic medicine

A disclaimer first — herbal supplements and Ayurvedic medicines are not synonymous.

The ongoing COVID-19 pandemic shows that age, co-morbidities and the quality of available healthcare impact the rate of recovery. Given that no vaccine or targeted therapeutics for COVID-19 are in ready sight, India’s Ministry of AYUSH, which focuses on traditional Indian medicines including Ayurveda, has called attention to traditional medicines for alleviating symptoms of COVID-19¹. However, in the absence of scientific evidence of cure and safety, Ayurvedic medicines cannot become part of the standard of care for COVID-19 therapy or management. Can there be a way forward toward scientifically rigorous examination of potential benefits of Ayurveda in COVID-19 management or therapy?

The advertized benefits of herbs in many Ayurvedic products fall in the realm of nutritional supplements where wellness industries thrive. Such wellness products neither claim, nor are their regulatory approvals based on, any definitive therapeutic, medicinal or disease curative benefits. Ayurvedic medicines should not be confused with nutraceuticals, the latter only means food supplement with potential health benefits. Ayurvedic medicines or formulations on the other hand are prescribed by practitioners who claim a curative therapy against a given disease.

And therein lies the barrier to their acceptance as scientifically proven safe medicines for the disease in question: traditional medicinal mitigation of severe acute respiratory infections (SARI), like COVID-19, have not been scientifically proven^2,3.

Reductionism and the streetlight effect in validating Ayurveda

While traditional medicines from Ayurveda or traditional Chinese medicine (TCM) encompass the use of traditional medicinal concoctions, they are also are known sources of discovery for phytopharmaceuticals^4,5: that is, individual chemicals isolated from a given medicinal herb that can mitigate a disease or its associated symptoms. In the latter approach, chemists try to identify the key molecules from a herb for its ability to mitigate, say, disease symptoms that are demonstrable in an animal model or in cell lines — in the parlance of the conventional drug industry, they seek the active pharmaceutical ingredient. Recent approval for a clinical trial of phytopharmaceuticals for COVID-19 is one such example⁶. The molecule, AQCH, is derived from the broom creeper Cocculus hirsutus , a plant traditionally used for its medicinal benefits.

Pursuing such a ‘reductionist’ methodology is not surprising since mechanisms of actions of individual phytopharmaceuticals are relatively easier to resolve than those of Ayurvedic medicines, which are often combinations of multiple herbs that are believed to act in synergy and prepared by complex traditional methods. And the merit of a reductionist, phytochemical, approach is not unfounded. The anti-malarial drug, artemesinin, after all was discovered by this approach, starting with a medicinal herb Artemisia annua⁷.

Therefore, approaches to discover phytopharmaceuticals from traditional medicines, TCM or Ayurveda, are likely to bring tangible rewards when pursued with sufficient scientific rigour. These promises notwithstanding, this approach may hit a road block when seeking a treatment for COVID-19, in which clinical presentation of patients is complicated by co-morbidities that are unlikely to be addressed by a single phytopharmaceutical agent.

Moreover, this approach to phytopharmaceutical discovery calls to mind Noam Chomsky’s observation on the scientific method: “Science is a bit like a joke about the drunk who is looking under a lamppost for a key that he has lost on the other side of the street, because that is where the light is. It has no other choice”.

Thus, when pathogenesis is partly recapitulated in a cell line, its mitigation by a given phytopharmaceutical is considered therapeutically relevant — what is visible under the ‘streetlight’ of a screening procedure. Other potentially useful phytopharmaceuticals — epistemologically speaking — are then discarded by ignorance.This approach is also antithetical to Ayurvedic principles wherein the totality of the entire medicine/formulation cannot be reduced to its individual components. By the same Ayurvedic rationale, what a patient suffers is the sum total of a host of bodily manifestations, which cannot be reduced to only a single symptomatic manifestation.

Repurposing Ayurvedic medicines

Ayurveda is founded on traditionally inherited knowledge and is based on empirical evidence. Given the recent origin of COVID-19, an Ayurvedic treatment is therefore not available. New Ayurvedic medicines also cannot be discovered — unlike in a drug discovery programme of conventional medicine. Thus, cure or management for COVID19 — if these were to be found in Ayurvedic pharmacopeia of India — would fall under the category of drug repurposing or therapeutic switching, again, in the parlance of the pharmaceutical industry.

The concept of repurposing of medicine is not alien to Ayurveda. The list of medicines, or the combination thereof, that an Ayurvedic practitioner may use to treat symptoms of COVID-19 is not inexhaustible and most practitioners would make overlapping, if not identical, recommendations from the available list of Ayurvedic medicines. Their choice of medicines would be guided by the framework of mapping pathogenesis set out in Ayurvedic classifications of a patient’s constitution and the co-morbidities presented, along with those of COVID-19. Even within this finite choice of medicines, the prescriptions will be customized for individual patients: indeed, there is no universal fit in Ayurvedic therapy.

However, one needs to ask whether such rationale and personalized procedure for Ayurvedic therapeutics could be timely and effective during a pandemic. While one can draw a rosy picture of traditional medicinal panacea for COVID-19, the realities could be challenging. COVID-19 symptoms can escalate precipitously in many patients, requiring emergency care, foreclosing the option of slow-acting Ayurvedic interventions. Also, here is cautionary advice against the use of herbal or traditional medicines for COVID-19^2,3 even though their potential is documented^4,5.

A clinical trial on Ayurvedic COVID-19 management?

Thus, while Ayurvedic treatment for COVID-19 cannot be suggested, the opportunity presented by the pandemic could be used to rigorously design clinical trials to test the claims of Ayurvedic medicine. Many COVID-19 positive patients display mild symptoms and recover under quarantine with no further treatment, since none may be available yet. These patients, not requiring hospitalization, could form ideal cohorts for randomized control trials to validate Ayurvedic alleviation of COVID-19. A clear and realistic definition of anticipated outcomes from such clinical trials and their rigorous design might answer questions including whether Ayurvedic therapy can help early and improved recovery of COVID-19 patients, or whether such an intervention can reduce the number of patient requiring critical care.

Animal models

Safety and toxicity assessments of Ayurvedic medicines are possible using the standards of evaluation practiced in mainstream pharmaceutical sciences: for instance, by using animal models to assess toxicity and also recapitulation of severe acute respiratory infections in mouse models for testing actual mitigation.

Ayurvedic medicinal claims can also be tested in carefully constructed animal models of human diseases to assess the cross-talk between Ayurvedic medicines and immune system and gut microbiome, an over-looked field, to reveal as yet mysterious ways of working of Ayurvedic medicines. Quality assurances to overcome the varying medicinal properties of plants under different geographical conditions can also be resolved.

These steps can address the major concerns about efficacy and safety of Ayurveda, while technological breakthroughs in the coming years may turn on the many streetlights to illuminate the space of complex Ayurvedic formulations.

(*Jitendra Kumar is from the Bangalore Bioinnovation Center, Bengaluru and **Pradip Sinha is from the Indian Institute of Technology Kanpur.)

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References

1. Ministry of AYUSH. Government of India Gazette notification F. No. L1101/8/2020/AS (21 April 2020)

2. Cyranoski, D. China is promoting coronavirus treatments based on unproven traditional medicines. Nature (2020) doi: 10.1038/d41586-020-01284-x

3. Yang, Y. Use of herbal drugs to treat COVID-19 should be with caution. Lancet 395, 1689–1690 (2020)

4. Redeploying plant defences. Nature Plant. 6, 177 (2020) doi: 10.1038/s41477-020-0628-0

5. Cui, H.-T. et al. Traditional Chinese medicine for treatment of coronavirus disease 2019: a review. Traditional Medicine Res. 20, 65–73 (2020) doi: 10.12032/TMR20200222165

6. ICGEB with Sun Pharma: Phase-II clinical trial on AQCH for treatment of COVID-19 patients. Press Release

7. Tu, Y. From Artemisia annua L. to Artemisinins, Elsevier (2017)