Kerrie L Oakes,1 MSWAP, Paul R Saunders,2 Phd, ND, Iva Lloyd,3 ND, Tiffany Turner,4 ND, Janis Gruska,5 ND, Belinda Gibbs,6 MScANM, Sophie Gleitzman,6 B Hsc Naturopathy, Caio Fabio Portella,7 MScPH, Jamie Friend,8 B Hsc Naturopathy, Kim Graham,9 ARCCIM, and Meagan Leslie,10 Cert IV TA
ABSTRACT
Background: Most systems of traditional medicine have been using herbal medicines to prevent and treat acute respiratory conditions and various other conditions for centuries. The aim of this project is to identify and examine the systematic and narrative reviews reporting on the therapeutic use of herbal medicines as it relates to the prevention and treatment of COVID-19 and long COVID.
Methods: This paper is part of an umbrella review of studies related to natural health products and natural therapies for the prevention or treatment of COVID-19. It is a follow-up to a live review that was conducted by the World Naturopathic Federation between May 2022 and May 2023. PubMed and Google Scholar were searched for systematic and narrative reviews that met defined quality criteria.
Results: Over half of the initial systematic reviews were excluded as they did not meet the inclusion and AMSTAR criteria. The final paper included 25 narrative reviews and 41 systematic reviews (SR), with half of the SRs reporting on the safety of herbal interventions. Various therapeutic properties of over 60 herbal medicines were outlined, some individually and most of them as part of herbal formula (combinations).
Conclusion/Summary: Herbal interventions demonstrated statistically significant improved recovery in patients with COVID-19. The most common therapeutic properties identified were immunological properties, anti-inflammatory, anti-microbial, and antioxidant while the most frequently investigated herbs were Glycyrrhiza glabra/uralensis, Tinospora cordifolia, and Curcuma longa. More attention is needed on the regulation of herbal medicines, the quality of research, and the safety of herbal medicines.
Key Words Traditional medicine, effectiveness, complementary medicine, immune health, Chinese medicine, coronavirus
Herbal medicine is a core component of traditional and complementary medicine worldwide.1,2 Traditional systems of medicine, including Ayurveda, Caribbean, First Nations and Indigenous, Kampo, Traditional Chinese (TCM; see Appendix 1 for a glossary of terms and acronyms used in this manuscript), Tibetan, and Unani systems, among others, all employ herbal products or extracts in the treatment and prevention of disease. More than half of visits to naturopathic practitioners result in a form of herbal prescription.2 Herbal medicines include materials, preparations, and products that contain all or parts of plants, fungi, lichen, and/or algae to prevent and treat disease.2,3 Herbs can be prescribed internally as part of diet, as teas, tinctures, essential oils, or tablets/capsules, and can also be used topically in creams, oils, poultices, and compresses2.
Herbal medicine has historically been used for upper respiratory tract infections and immune health. Identification of treatments and preventive strategies for COVID-19 (severe acute respiratory syndrome coronavirus 2 – SARS-CoV-2) became a focus for international research following its emergence in early 20204 and traditional and complementary medicine (T&CM) researchers have contributed to the body of research that outlines the role of herbal medicine for the prevention and treatment of COVID-19 and the management of post-COVID syndrome.4
Research conducted prior to, and early in, the emergence of COVID-19 suggested that commonly used herbal medicines may contribute to the prevention and treatment of COVID-19 and management of post-COVID syndrome. For example, Aucoin et al.,5 noted that the role of Echinacea with respect to the treatment and prevention of respiratory diseases has been researched for over a century and that it is a major component of commercially available herbal medicine products. Its immuno-modulatory properties contribute to its popularity for immune support.5 Similarly, Hedera helix preparations have been commonly used for the treatment of early symptoms of acute inflammatory respiratory conditions, particularly coughing, in both adults and children.1 Clinical studies of preparations of sambucus nigra, conducted prior to the pandemic, indicated that it may reduce the duration and severity of influenza and the common cold, particularly when taken within 48 hours of symptom onset.6
Interest in the role of natural health products (NHPs) generally, and herbal medicine specifically, in the prevention and treatment of COVID-19 grew during the global pandemic as evidenced by the growth in research attention throughout the period of the live review.4 A range of herbal interventions have been studied, both individually and as patent formulae.4
Evidence collected early in the emergence of COVID-19 suggested that herbal medicine had a valuable role in the prevention, treatment, and management of COVID-19 and post-COVID syndrome. However, much of this evidence for the benefit of herbal medicine was extrapolated based on its use in broad respiratory/immunological conditions in the absence of COVID-19–specific knowledge. The objective of this paper is to review and synthesize the published peer-reviewed narrative and systematic reviews on the use of herbal medicine to prevent or treat COVID and identify key considerations for future research and clinical application of herbal medicine.
This report follows from the live review conducted by the World Naturopathic Federation (WNF) and the Canadian College of Naturopathic Medicine (CCNM) from May 2022 to May 2023. It is part of an umbrella review instigated by the WNF to examine and report on the NHPs and therapies that were being researched with respect to the prevention and/or treatment of COVID-19 and post-COVID.
Throughout the live review, monthly literature searches were undertaken following the Cochrane Guidelines for a Living Systematic Review. Both PubMed and Google Scholar databases were included, with search terms including “natur*,” “herb*,” “nutraceutical,” “botanical,” “medicinal plant,” “Ayurvedic,” “Chinese medicine,” “herbal patent formula,” combined with “prevention,” “prophylaxis,” “deficiency,” “treatment,” “management,” and “*COVID*,” “Coronavirus,” “SARS-CoV-2.” Individual plant names and compounds cited in the literature were also searched. Articles were grouped based on the type of review—systematic, narrative, meta-analysis, and others.
Both systematic reviews and narrative reviews were included in this study. Systematic reviews were reviewed by 2 blinded reviewers based on the A Measurement Tool to Assess Systematic Reviews (AMSTAR) guidelines.7 Reviews were included where a satisfactory Risk of Bias (RoB) technique for assessing risk in individual studies was used and if the study accounted for the RoB of individual studies in interpreting or discussing the review results.7 Narrative reviews were reviewed based on the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines.8 Reviews were included if a scientific reasoning score of 1 or 2 was noted AND an overall total sum was >5. A separate reviewer verified inclusion/exclusion where there was a discrepancy for the inclusion questions. A reference overlap analysis was also conducted to ensure that the results of any single study were not overstated. Included articles were published in English. Inclusion criteria are outlined in Table 1.
TABLE 1 PICO Inclusion Criteria
Data was extracted only for those studies that were statistically significant, and only for those outcomes relevant to NHPs/therapies. As with the living review, online spreadsheets were used to collate included studies and collate extracted data.
For narrative reviews, the recorded data included study number, study identification, author(s), date of publication, journal, country/WHO region, review objective, details of any search conducted, area of focus (prevention, treatment, or post-COVID management), dosages, therapeutic considerations, including herbal properties (anti-inflammatory, antiviral, etc., as per https://www.ndhealthfacts.org/wiki/Action_of_Herbs), associations (relationship to other NHPs), therapeutic considerations, and additional clinical notes.
For systematic reviews, the data recorded included study number, study identification, author(s), date of publication, journal, area of focus (prevention, treatment, post-COVID), review objective, review type (systematic or meta-analysis), search date, search databases, study designs, country of included studies, WHO region, publication date range of studies included within the systematic review, tools for assessment of risk of bias, and methods of synthesis/analysis. Study results recorded included interventions relevant to herbal medicine, measured outcomes (rate of recovery (ROR) for key symptoms such as fever, cough, dyspnea; rate of conversion (ROC), such as duration of hospital stay, mortality, etc., imaging, laboratory testing measures, and adverse reaction reporting (ARR)), the number of studies, participant characteristics such as the number, age average or range, and gender percentages, results, and heterogeneity (where meta-analysis was conducted).
A total of 123 papers (24 narrative reviews and 99 systematic reviews) were retrieved for inclusion/exclusion screening. One additional narrative review was retrieved and included following initial screening.
Although umbrella reviews do not typically include narrative reviews, these potentially provide broader information useful for considering potential clinical implications, such as for diagnosis and treatment.9 Twenty-five narrative reviews10–34 were included in this project (Table 2). Most (n = 16)10,11,13–17,20,21,25–28,32,33,34 focussed on treatment of COVID-19 while a further six (6)12,18,19,22–24 papers examined both prevention and treatment and one (1)29 examined prevention, treatment, and post-COVID syndrome. Additionally, two (2)30,31 papers examined the use of herbal medicine as an adjunct for COVID vaccination. WHO world regions represented included the Americas (n = 9), South-East Asia (n = 5), Western Pacific (n = 5), Eastern Mediterranean (n = 3) and European region (n = 3). A broad range of herbs, used in Ayurvedic, Traditional Chinese, Thai, Tibetan, and Western naturopathic systems of medicine used in the prevention and treatment of COVID-19 and post-COVID syndrome were examined.
TABLE 2 Overview of Studies: Narrative Reviews
After the inclusion/exclusion screening phase, 51 systematic reviews were included for data extraction. During data extraction, a further 10 systematic reviews were excluded. In total, 41 systematic reviews35–75 examining the contribution of herbal medicine were included in this umbrella review (Tables 3 and 4). The focus of the systematic reviews was treatment of COVID-19 (n = 40). Most of the research originated from the Western Pacific (n = 30). As with the narrative reviews, a variety of herbal interventions were considered in the systematic reviews. Most (n = 32) examined patent herbal formulas either alone or in conjunction with other interventions. All systematic reviews identified specific tools for assessing risk of bias (RoB). Eleven studies35,45,46–48,55,61–63,67,75 reported that studies had moderate to high reported RoB. Factors reported as contributing to high RoB included lack of information regarding blinding or randomization, problems with measurement of outcomes and selective reporting, selection bias, and small sample size.
TABLE 3 Overview of Studies: Systematic Reviews
TABLE 4 Overview of Results: Systematic Reviews
The degree of citation overlap across the 41 systematic reviews included in this paper is 3.8% (268 individual references, in 687 unique instances across 41 total systematic reviews). Overall, this would be considered a slight overlap. Twenty-seven35,37–55,60,61,64,65,68–70 out of the 41 systematic reviews included in this paper (67.5%) contained 5 or more articles cited more than once across all included reviews (see Table S1 in the supplemental material). All these reviews studied TCM, including patent TCM herbal formulas. This represents 27 out of the 32 total reviews that studied TCM herbal formulas. One review38 also examined herbs used in the Ayurvedic system of medicine. We determined that the impact any occurrence of overlap would have on our review findings was high. This means that findings related to TCM should be interpreted cautiously to consider the possible duplication of findings reported across the reviews citing the same papers.
Twenty-five35,37–39,41–45,47,48,51–55,57,60,65,66,68,69,70,72,74 of the systematic reviews found significant improvement in ROR, based on one or more of the symptoms associated with COVID-19, primarily fever, cough, fatigue. Other ROR that improved included chest pain, sore throat, and expectoration. Reduction in ROC, especially as it related to duration of stay in the hospital, was reported as significant in 19 of the systematic reviews37,38,40,41,43–45,48–50,51,53,54,56,57,59,68,69,70 and indicated as insignificant in four reviews.38,43,61,67
Most systematic reviews indicated significant improvements in lung computed tomography (CT) scan readings. Fifteen reviews37,39,42,43,46,47,51,52,54,58,60,65,68,70,73 indicated significant improvements in other laboratory measures, such as viral nucleic acid levels, inflammatory markers, and reverse transcription polymerase chain reaction (RT-PCR) negativity. Some studies50,51,54,63,67,73 reported that there were no significant improvements in measures of viral clearance,63 nucleic acid test,50,51 or pro-inflammatory markers.54,63
The two narrative reviews on curcumin27,29 (derived from Curcuma longa) highlight the antiviral, immunomodulatory, and anti-inflammatory properties of curcumin. Other aspects identified which may contribute to therapeutic benefit in the prevention and/or treatment of COVID-19 are curcumin’s antioxidant,29 anticoagulant,29 antiplatelet,29 and cytoprotective29 properties. The potential role of curcumin in the prevention and treatment of COVID-19 and the management of post-COVID syndrome were indicated as viral inhibition or inactivation by binding directly to receptors on the spike protein and ACE-2 receptors,27,29 regulation of the PI3K/Akt/mTOR signaling pathway,27 and alleviation of pulmonary fibrosis.27
Five systematic reviews evaluated the effects of curcumin supplementation on patients with COVID-19.35,58,59,72,73 Studies reviewed included randomized controlled trials (RCTs), intervention studies, clinical studies, and non-randomised clinical trials. Two papers performed meta-analyses and two were descriptive studies. Dosage and type of intervention varied between the studies. All studies included curcumin as an adjunct to standard care. Four studies examined supplementation with nano-curcumin at dosages ranging between 40 mg and 240 mg for periods ranging from 7 to 21 days. Administration of other forms of curcumin supplementation (oral spray, tablet, AyurCov preparation) included dosages ranging from 40 mg to 950 mg, either as standalone or in combination with other NHPs, over durations ranging from 14 to 21 days. The outcomes examined included all-cause mortality,58,75 effect on lymphocyte count,58 cytokine levels,58 gene expression of transcription factors,58 mechanical ventilation,72 hospitalisation,72 and positive RT-PCR.72 Statistically significant differences between curcumin intervention and comparator showing the benefit of curcumin included reduction in mortality,59,73 lower rate of positive viral PCR test,73 and faster rate of recovery.73 Improvements in lymphocyte count58 were reported; however, the statistical significance of this effect was not reported. Supplementation with nano-curcumin was found to potentially reduce the duration of hospitalisation and provide symptomatic relief of COVID-19.73
The narrative review on Withania somnifera23 highlighted its antiviral properties. The proposed role of Withania in the prevention and treatment of COVID-19 related to its major constituents of withaferin A (wifA) and withanone (win). The study reported that the cytotoxicity of the main proteases of SARS-CoV-2, (Mpro), which was vital for viral replication, was reduced by both wifA and win. Both components irreversibly inhibited 0.5 μM Mpro with IC50 values of 0.54 and 1.8 μM, respectively.
No systematic reviews reported solely on the use of Withania somnifera in the prevention or treatment of COVID-19. One systematic review reported on its use as a component of an Ayurvedic herbal treatment (see below).
The ten narrative reviews10,12–14,16,19,20,25,32,33 that examined herbs used in traditional Chinese,10,12,13,14,16,19,32 Tibetan,33 and Thai10 medicine, and Ayurveda12,20,25 highlighted the antiviral,10,13,14,16,20,25,32,33 anti-inflammatory,10,13,32,33 immunomodulatory,12,13,14,16,20,33 and hepatoprotective16 properties of a broad variety of herbs and formulations.
The potential role of these herbs in the treatment of COVID-19 included the multi-component nature of some traditional formulations, contributing to a multi-targeted action against viral infections, cytokine storms, endothelial injury, and micro-thrombotic impacts of variants of SARS-CoV-2.16
Four systematic reviews reported on the effects of Ayurvedic medicine in the treatment of COVID-19.38,63,67,71 The types of studies included were RCTs and quasi-RCTs. Herbal interventions included granules, decoctions, tablets, nasal drops, and injections. Studies included in the systematic reviews examined Ayurvedic herbal medicine as adjunct to standard care,38,63,67,71 as a standalone treatment,38,67 or compared with placebo or placebo plus Western medicine.38
Dosage and interventions varied across the studies. The polyherbal AYUSH-64 formulation was administered at a dosage of 1 g either twice or three times daily. Other formulations included Guduchi Ghanavati, two tablets (250 mg each), twice daily; Chyawanprash, 12 g twice per day for 30 days; and polyherbal approaches reported as AYUSH regimens, comprising different herbal combinations at varying strengths, administered twice daily (see Table S2 in the supplemental material). Duration of administration ranged from 7 days to 12 weeks.
Outcomes examined included effect on RT-PCR negativity, clinical symptoms (fever, cough, chest pain, throat, fatigue, chest computed tomography [CT]), duration of hospitalization, laboratory parameters (white blood cell [WBC] count, lymphocyte counts and percentages, C-reactive protein, IL-6, erythrocyte sedimentation rate [ESR]), disease progression (including resultant admission to high-dependency or emergency units), recovery time, and mortality. Adverse effects of herbal treatment were considered in two studies.63,67
Study results suggested that administration of Ayurvedic herbal formulations, including AYUSH-64, Guduchi, and Kabasura Kudineer, performed better as an adjunct to Western medicine when compared with Western care alone, particularly in mild, moderate, or asymptomatic cases.38,67,71 Ayurvedic herbal medicine treatment when used as an adjunct showed improved symptom recovery rate, and improved laboratory parameters.71
In total, 32 systematic reviews considered the role of patent herbal formulas in the treatment of COVID-19.35,36,38–57,60–62,64–66,68–70,74 Herbal formulations studied included decoctions, granules, pills, patent formulas, or injections (see Table S3 in the supplemental material). All papers focused on treatment, with none reporting on prevention or management of post-COVID syndrome.
Reporting of patient data was inconsistent. Nine papers did not include patient age data, while 11 did not include gender information. Age reporting included various measures, such as mean age, age range, or average age. The average age ranged between 45 and 65, with an overall age range between 17 and 86 years. Where gender was reported, patients were predominantly male, although one paper reported higher female inclusion. Gaps in data availability were attributed to the number of studies only available in the Chinese language. All patients included were identified as having COVID-19 ranging from mild to critical.
All papers reported on the use of CHM as an adjunct to standard treatment. Three papers also reported on CHM as a stand-alone treatment compared with standard treatment.57,60,62 Administration of interventions variously occurred over a duration ranging from 3 to 30 days, with dosages varying depending on the nature and type of CHM formulation.
Outcomes examined included clinical effects of herbal medicines as measured by changes in clinical symptoms, recovery time and rate, duration of hospitalization, changes in disease severity, and the progression of disease. Outcomes related to changes in laboratory measures and inflammatory markers, including WBC count, lymphocytes, C-reactive protein, IL-6, ESR, nucleic acids, and viral assays, were examined. Some studies also examined lung injury as evaluated by x-ray or chest CT. The safety of TCM interventions was examined, including adverse reactions, increased severity of disease, and mortality rates.
Results indicated that the use of TCM herbal interventions as an adjunct to Western treatment yielded better recovery rates for COVID-19 clinical symptoms and reductions in recovery time from COVID-19. Statistically relevant results included resolution of COVID-19 symptoms,38–40,42–45,47–49,51,53–55,57,65 improvement in lung function, inflammatory markers, and other laboratory results,40,42–44,46,47,51,52,54,60,66,68 reduction in duration of hospitalization,40,44,53,68 and improved clinical cure rate.44,48–51,68
The narrative reviews examining other medicinal herbs14,15,26,28,34 also highlighted anti-inflammatory, antioxidant, antiviral, immune enhancing, immunosuppressive, central nervous system modulating, and immune modulating actions of medicinal herbs. The proposed mechanism of action of medicinal herbs in the treatment of COVID-19 was suggested as being due to the secondary metabolites present in these plants, including sterols, diterpenes, alkaloids, glycosides, and aliphatics.14,34
One systematic review75 considered the role of glycyrrhizic acid preparation (GAP) in the treatment of COVID-19 alone and COVID-19 with comorbid liver injury, particularly in relation to its efficacy and safety.75 The study reported that GAP contributed to a reduction in liver enzymes and CRP while improving liver function, inhibiting inflammation, and strengthening immunity. Some mild adverse reactions were reported although the impact of co-administration with antiviral drugs was not investigated.
One narrative review17 focussed on potential toxicity of herbs sometimes used in traditional medicine. This review highlighted the importance of use by appropriately qualified practitioners. No systematic reviews specifically examined the potential toxicity of herbal medicine in relation to treatment or prevention of COVID-19 or in the management of post-COVID recovery.
Two narrative reviews examined the role of herbs as vaccination adjuncts against COVID-19.30,31 These reviews considered preclinical studies of the use of plant proteins as immunoadjuvants in antiparasitic, antifungal, and antiviral vaccines. Immune-modulating and immune-enhancing properties were identified. The potential role of plant proteins in binding to carrier proteins may attenuate potential toxicity of some adjuvant immunization formulations for pediatric and immunocompromised patients30. It is proposed that the mechanism of action is related to immunostimulatory activity, such as enhancement of T lymphocyte proliferation,30,31 and amplification of production of IL-12 and IFN-gamma.30 No systematic reviews examined the use of herbal medicine for vaccination purposes.
Over 50% of the original systematic reviews focusing on the use of herbal medicines for the prevention and/or treatment of COVID-19 were not included in the final papers as 49.5% did not meet the AMSTAR criteria set for this umbrella review and another 10.5% were removed during the data extraction phase as they did not meet inclusion criteria (not COVID [n = 4], duplicate [n = 2], not herbs [n = 2], not English [n = 1], wrong study type [n = 1]). Uncertainty about the quality of research on herbal medicines is a recognized concern76 and impacts the understanding and acceptance of herbal medicines from all traditional medicine systems. For example, concerns exist regarding the variability of plant chemical compositions depending on the part used, botanical species, and growing and harvesting conditions, among others in herbal research.76,77 Likewise, concerns about the level of methodological reporting, such as the absence of information about blinding, random allocation, and low sample sizes, have previously been identified.77
Various studies included in this paper examined herbal medicines used in traditional medicine systems—particularly those of TCM and Ayurveda. Herbal medicines are used alone and in conjunction with conventional Western medicine for most health concerns, especially those related to acute infections and non-communicable diseases (NCDs).77,78,79 Understanding the effectiveness and safety of herbal medicines is critical as they are used as an integral part of most traditional systems of medicine, including Indian systems of medicine 80 and Traditional Chinese medicine (TCM), and over 93% of the naturopathic medical workforce globally uses herbal medicines 2,81 and indicated that the study of herbal medicines was part of their naturopathic medical education. With the use of herbal medicines so integral to traditional medicine practices, it is concerning that, according to the WHO Global Report on Traditional and Complementary Medicine 2019, 110 member states indicated the use of herbal medicines, but only 24 indicated that there was any regulation.3 The lack of regulation impacts the safety, quality, and efficacy of herbal medicines both for practitioners who use them in practice and the public that is self-prescribing.
The studies in this paper explored the pharmacological aspects of various herbal medicines in the prevention and treatment of COVID-19 and long COVID, including immunological, anti-inflammatory, anti-microbial, and antioxidant properties. The wide range of herbs investigated, and the diversity of the properties explored highlight the significant role that herbal medicines can play, especially in the treatment of acute conditions, such as COVID-19. Many papers highlighted the role of herbal medicine as an adjunct to Western care (n = 40). Herbal interventions, when used as an adjunct, demonstrated statistically significant improved recovery, including symptomatic resolution, improved inflammatory markers, reduced hospitalization, and improved clinical cure.
Various studies noted herbal medicine’s inhibitory impacts on viral activity. This includes blocking of invasion pathways, suppression of cytokine storm potential and degradation of lymphocytes. Herbal constituents such as curcumin, essential oils, naringin, pectins and flavonoids can bind directly to receptors. The cytotoxicity of Mpro (required for viral replication) was inhibited by constituents of Withania. The anti-inflammatory properties of herbal constituents, including sterols, diterpenes, alkaloids, glycosides, and cannabinoids, contribute to modulation of inflammatory processes, including ACE2 gene expression, and reduction of serum CRP, MDA, and TNF-alpha.
Enhancement of vaccination through adjunctive use of herbal medicines with immunomodulatory and immuno-enhancement properties was suggested by two studies in this review. This is an aspect of the potential of herbal medicine that warrants further study, given the immuno-stimulant activity of various herbs.
A significant finding, particularly among the reviews of CHM interventions, was the added benefit of herbal treatment to patient outcomes when botanicals are combined with standard care or Western medicine. Objective laboratory measures showed statistical improvements within complete blood counts (CBC) (white blood cells [WBS], lymphocytes), CRP, and other measures of inflammation. Relief and reduction of COVID-19 symptoms and the rate of conversion, especially in relation to the duration of stay in hospital and viral clearance, was also evidenced. Combining herbal medicine with standard treatment thus may reduce overall cost of treatment through better patient response to treatment and improvements in recovery from illness.
Although >60 individual herbs were included in the papers surveyed in this report (see Appendix S1 in the supplemental material), a few herbs stood out due to the frequency with which they were investigated (including as key components of herbal formulations in TCM and Ayurvedic preparations), the findings associated, and their widespread use in herbal medicine. Three key herbs highlighted are Glycyrrhiza glabra/uralensis, Tinospora cordifolia, and Curcuma longa.
Glycyrrhiza glabra/uralensis (licorice) is a key herb in seven of the TCM herbal formulations studied in this review. Its medicinal use has been documented in texts from ancient Assyria, Egypt, China, and India.83 Glycyrrhizic acid (GA) is one of the main active ingredients in licorice. Studies have demonstrated the role of glycyrrhizic acid preparations (GAP) in inhibiting growth of coronaviruses,82,83 influenza A,82,83 and HIV.82,83 GA has demonstrated activity in chronic liver disease, inhibiting collagen type 1 alpha 2 (COL1A2), and slowing the progression of liver fibrosis.82 Anti-viral actions include interference with the S-protein, inhibiting viral entry to host cells, adsorption and membrane penetration during viral replication, and stimulation of IFN-gamma development by T-cells.82 As an anti-inflammatory, GA inhibits translocation of nuclear factor-κB (NF-κB) and suppresses TNF-alpha.83
Tinospora cordifolia (guduchi) is widely used in Ayurvedic medicine.84 Classical Ayurvedic texts indicate its usefulness in various disease conditions, including those characterised by fever, nausea, and cough.84,85 It contains a variety of compounds, including alkaloids, glycosides, sterols, and polysaccharides.85 Preparations of the dried stem have demonstrated an anti-inflammatory mode of action that resembles that of nonsteroidal anti-inflammatories.84 Studies have indicated it can normalize liver function84 and that it activates the immune system via actions of (1,4)-alpha-D-glucan on macrophages, activating them via TLR6, NF-κB and cytokine production.84,85
Curcuma longa (turmeric) is a key source of curcumin and has been used medicinally in many parts of the world.86,87 While bioavailability has been identified as reducing the effectiveness of curcumin, most preparations contain such enhancers as piperine (also found in black pepper, Piper nigrum).86,87 Evidence demonstrates that curcumin can address oxidative stress, which is a factor in chronic disease and inflammation.86 Curcumin’s anti-inflammatory actions have been shown to result from its capacity to block activation of NF-κB.86 Potentially, it also increases the activity of antioxidants.86 Curcumin has demonstrated activity targeting multiple signalling molecules.86 It directly targets protein kinases, inflammatory molecules, carrier proteins and metal ions.87 Indirectly, it targets enzymes, transcription factors, receptors, inflammation mediators, adhesion molecules, and growth factors.87 This broad range of activities contributes to the role of curcumin in treating and preventing various conditions.
Twenty systematic reviews in this paper considered the potential of adverse reactions in their study design.41,42,45,46,49,50,52–56,60,63–67,73–75 Most (n = 17) reported adverse reactions that were either mild or “not serious.” Reactions reported included diarrhea, vomiting, rash, and nausea. Two studies56,75 reported abnormal liver function results; however, both reported that methodological limitations reduced the certainty of the impact on safety of herbal treatment when used in conjunction with standard treatment. Three studies54,60,63 reported that inclusion of herbal medicine with standard treatment tended to reduce side effects. One study75 specifically noted that the impact of combining herbal and chemical anti-viral drugs was not known.
As noted above, the global lack of regulation impacts the safety of herbal medicines.3 A range of safety considerations have been identified, including lack of methodologically sound research regarding interactions between medications (herb–drug, and herb–herb),77 adulteration of herbal material,77 variable product quality,76,77 and cultural contexts, such as communication gaps between patient and practitioner.76,77
Various factors contribute to herbal medicine safety. For example, chemical composition can vary depending on the growing conditions, parts used, how and when plants are harvested, preparation/extraction, and formulation of medicinal products.76 Clinically based research demonstrates that naturopathic practitioners have a high level of knowledge regarding herbal safety issues, making them well-placed to provide support for patients in making appropriate choices.2
There are some limitations to this review. The methodology for this umbrella review focused on papers with a strong methodology. Several of the papers reviewed reported poor methodological quality, including risk of bias in the studies that they reviewed. Building a body of knowledge demonstrating the effectiveness and safety of herbal medicine requires increased attention to conducting high quality research. Another limitation was the wide variety of herbal medicines included in the review. While this provided a useful overview of the range of herbs that could be used for the prevention, treatment, and management of COVID-19, the range of interventions used made the identification of key herbs and treatment approaches challenging. The lack of systematic reviews considering the role of herbs in the prevention of COVID-19 highlighted a gap in research relating to the benefit of herbal medicine in enhancing the human immune system to prevent disease.
Herbal medicines are the most prevalent therapy used in most traditional medicine systems, yet there remain concerns about the safety of herbal medicines, the lack of regulation in many countries, and the quality of research conducted on herbal medicines. That being said, half of the studies in this paper reported on adverse research, 85% of which reported only “mild” or “not serious” reactions.
The papers included investigated over 60 herbs and highlighted a broad range of therapeutic properties, including immunological, anti-inflammatory, anti-microbial, and antioxidant properties as they highlighted the significant role of herbal medicines in the prevention and treatment of COVID-19 and long COVID and in vaccination enhancement. Three key herbs were highlighted: Glycyrrhiza glabra/uralensis, for its potential to inhibit the growth of coronavirus, the anti-inflammatory and immune-enhancing properties of Tinospora cordifolia, and the oxidative stress and anti-inflammatory properties of Curcuma longa. What appeared to be evident in this review is that herbal interventions, when used as an adjunct to standard care, demonstrated statistically significant improved recovery including symptomatic resolution, improved inflammatory markers, reduced hospitalization, and improved clinical cure.
1National Centre for Naturopathic Medicine, Southern Cross University, Lismore, Australia;
2Canadian College of Naturopathic Medicine, Toronto, ON, Canada and National University of Health Sciences, Lombard, IL, United States;
3World Naturopathic Federation, Toronto, ON, Canada;
4Canadian College of Naturopathic Medicine, New Westminster, BC, Canada;
5Bastyr University, San Diego, CA, United States;
6Independent scholar, Sydney, Australia;
7CABSIN: Brazilian Academic Consortium of Integrative Health, Sao Paulo, Brazil;
8The Friendly Naturopath clinic, Australia;
9Australian Research Centre in Complementary and Integrative Medicine (ARCCIM), University of Technology, Sydney, Australia;
10Endeavour College, Sydney, Australia.
The authors are grateful to Maria Karillis, Katrina Reeve, Hannah Richmond, Tracelee Shaw, Kristan Gilbert, Beth MacGregor, Tobey-Ann Pinder, Cathrina Geldard, Rebecca Boothe, and Gabrielle Covino for their assistance with the critical appraisal of articles included in this review. We also appreciate the editorial oversight and support provided by Dr Iva Lloyd, Dr Kieran Cooley and Associate Professor Amie Steel.
We have read and understood the CAND Journal’s policy on conflicts of interest and declare that we have none.
This research did not receive any funding.
Supplemental material linked to the online version of the paper at https://doi.org/10.54434/candj.161:
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Supplemental material for this article is available online at https://doi.org/10.54434/candj.161
Correspondence to: Kerrie L Oakes, 357 Glenhowden Road, Harlin, Queensland, Australia 4314. E-mail: kerrieoakes@gmail.com
To cite: Oakes KL, Saunders PR, Lloyd I, Turner T, Gruska J, Gibbs B, Portella CF, Friend J, Graham K, Leslie M, Gleitzman S. Herbal medicine and COVID-19: An umbrella review. CAND Journal. 2023;30(4):43-65. https://doi.org/10.54434/candj.161
Received: 10 September 2023; Accepted: 13 October 2023; Published: 28 December 2023
© 2023 Canadian Association of Naturopathic Doctors. For permissions, please contact candj@cand.ca.
CAND Journal | Volume 30, No. 4, December 2023