By Chukwuma Muanya
COVID-19 positive patients who took IHP Detox Tea ‘appeared to convert to negative status’ in relatively shorter time compared to those who did not
•WHO team visits clinical trials site, on ground for presentation of results, yet to make official statement on findings
Doctors have, in clinical trials, demonstrated that a blend of three local plants- King of bitters, bitter kola and guava- could be safely used to prevent, treat and ‘cure’ hospitalised COVID-19 patients.
King of bitters is locally called Jogbo because of its bitterness but popularly called Mejemeje (seven-seven) among Yoruba speaking natives in Nigeria.
Bioresources Development Group (BDG) developed the natural blend of King of bitters (Andrographis paniculata), bitter kola (Garcinia kola) and guava (Psidium guajava), called IHP Detox Tea.
The medical doctors are from the College of Medicine, University of Lagos (CMUL) and Lagos University Teaching Hospital (LUTH), Idi-Araba, Lagos State, and Nnamdi Azikiwe University Teaching Hospital (NAUTH) Awka, Anambra State.
Clinical trials are a type of research that studies new tests and treatments and evaluates their effects on human health outcomes.The presentation of the findings was made at CMUL/LUTH on Monday April 11, 2022 during the visit of the World Health Organisation (WHO) team to Nigeria to evaluate clinical trials conducted in the country for COVID-19 using traditional medicine or herbal medicinal products.
The key outcome was that the IHP Detox Tea studies at CMUL/LUTH and NAUTH were the only ones approved by the National Agency for Food and Drug Administration and Control (NAFDAC) undertaken in the country during the pandemic.
The IHP Detox Tea clinical trials showed clearly that the herbal product was effective in the treatment of COVID-19. With no single death recorded in the treatment group against three deaths in the control.
The work was a multidisciplinary project done as collaboration between University of Lagos (UNILAG), Nnamdi Azikiwe University (NAU), Awka, Anmabra State and Intercedd Health Products (IHP)- a subsidiary of BDG.
Summary of preliminary findings of CMUL/LUTH team, concluded: “COVID-19 positive patients who took the product appeared to convert to negative status in a relatively shorter time compared to those who did not. It appears that COVID-19 participants on IHP Detox Tea may be discharged earlier that those in control group.
“The IHP Detox Tea appears to be generally safe as one of the two participants with severe complaints could not be directly linked to the Tea with certainty.”
The clinical trial is titled “Special Blend of Andrographis paniculata; Garcinia kola and Psidium guajava L. [Myrtaceae]] for the Treatment of Coronavirus Disease [COVID-19]: A Study Pilot for a Randomised Clinical Trial and Primary Care.”
The Principal Investigator of the researchers from CMUL and LUTH, Prof. Edamisan Olusoji Temiye, is a Consultant Paediatric Oncologist/Haematologist.
Co- Investigators include: Professor/Consultant Haematologist, Suleiman Alani Akanmu; Professor/Consultant Cardiologist, David Adewale Oke; Professor/Consultant Medical Virologist, Sunday A. Omilabu; Senior Lecturer/Consultant Infectious Diseases, Prof. Iorhen Ephraim Akase; Associate Professor/Consultant Epidemiologist, Prof. Oluwakemi Odukoya; and Dr. Emmanuel Okafor as Study Manager.
A co-principal investigator of the study and a consultant Obstetrician and Gynaecologist at NAUTH, Dr. George Eleje, also presented results of clinical trials on “Efficacy and safety of IHP Detox Tea (a special blend of Andrographis paniculata, Garcinia kola and Psidium guajava) for treatment of COVID-19: a pilot randomised trial.”
The study concluded: “IHP Detox Tea has, thus, shown proven pharmacological efficacy in several of the conditions, which supports its potential beneficial use in COVID-19 patients.
“Apart from the proven antiviral effects of the components of IHP Detox Tea, the immune boosting and adaptogenic effects of the major phytochemical constituents will definitely contribute to better prognosis of COVID-19 patients placed on the proposed therapy.”
Regional Adviser, Traditional Medicine, WHO/African Region (AFRO), Ossy M.J. Kasilo, who was on a mission to Nigeria to Monitor Clinical Trials of Traditional Medicine-Based Therapeutics Proposed for the Treatment of COVID-19, between April 11 and 15, 2022, was at the public presentation of the research findings in CMUL/LUTH.
The discoverer and founder of IHP Detox Tea and Chief Executive Officer (CEO)/Founder of BDG, Prof. Maurice Iwu, was also at the public presentation.
Following approval by NAFDAC, with number A7-1951L, the IHP Detox Tea has been produced and marketed in Nigeria since 2016. Some components of IHP Detox tea like Andrographis paniculata have been shown to alleviate symptoms of acute respiratory tract infections in both adults and children, in addition to immune-stimulatory properties and anti-cancer activities components.
Earlier studies in 2017 had demonstrated that IHP Detox Tea has antiviral activities on earlier strains of coronavirus, Ebola virus, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV).
Severe Acute Respiratory Syndrome Coronavirus type two (SARS-CoV2) is the causative agent for COVID-19. Given its demonstrated ability to alleviate symptoms of acute respiratory tract infections in both children and adults, we hypothesise that IHP Detox Tea could have therapeutic or prophylactic properties against SARS-CoV-2 infection
Consequently, the researchers and the discoverer proposed to conduct a randomised clinical trial to assemble data supporting the beneficial or deleterious effect of IHP Detox Tea when co-administered with conventional therapy for treatment and prevention of COVID-19
The Guardian had last year reported that BDG, Abuja, Nigeria; International Centre for Ethnomedicine and Drug Development (InterCEDD) Nsukka, Nigeria, had submitted the previously NAFDAC listed IHP Detox tea for clinical trials.
Iwu, is a professor of pharmacognosy and President and Chief Executive Officer (CEO) of BDG, Abuja; International Centre for Ethnomedicine and Drug Development (InterCEDD) Nsukka, Enugu State and Bioresources Institute of Nigeria, Umuna, Onu-Imo, Okigwe, Imo State.
In his presentation, he said: “IHP Detox Tea has been in public use since 2016 and the reports from users of the products have been overwhelmingly positive.
“There are over 140 cases of people who used IHP Detox Tea and reported conversion from SARS CoV -2 positive to negative results. There are reports of many symptomatic cases that were resolved. Several health professionals use IHP – Detox Tea as possible pre- and post exposure prophylactic.
“But all these reports are treated as ‘anecdotal’ until the products are subjected to controlled clinical trials, which was conducted at LUTH with the approval of NAFDAC.”
The clinical trial was to be undertaken at the Nigeria Centre for disease Control (NCDC) COVID-19 isolation site in Lagos, Nigeria and has been registered with the Pan African Clinical Trials Registry: at www.pactr.org with registration number PACTR202004761408382.
The identified main bioactive phyto-constituents of the Andrographis paniculata are andrographolides while kolaviron; Garcinia biflavonoids has been reported in Garcinia kola.
The hypothesis is that combination regimen consisting of IHP Detox Tea and conventional care for COVID-19 are more efficacious than conventional care alone.
The study was conducted among patients being managed for COVID-19 at the LUTH COVID treatment centre. Study population are adult patients aged 18-60 years with clinical and laboratory diagnosis of the COVID-19 disease. Only patients admitted onto the COVID treatment wards were recruited.
Inclusion criteria were adult patients with confirmed clinical and laboratory diagnosis of COVID-19 disease and with the normal liver and renal function profiles; are between the ages of 18-60 years.
The Cycle Threshold (CT) for COVID-19 at recruitment must not be higher than 25. The patients must have signed off the written informed consent.
Criteria for exclusion were: pregnant, lactating and breastfeeding women; patients with serious ailments of heart, liver, kidney or brain; patients with chronic medical disorders including Human Immuno-deficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS), cancers etc.; subjects who have any allergy or were allergic to any of the medication to be used; and comatose patients or those unable to consume orally.
All participants underwent routine medical examination including: pulse rate; body weight; blood pressure; and general examination to ascertain the presence of and severity of the COVID-19 disease.
Eligible patients were sequentially allocated to receive either the IHP Detox Tea (one teabag to be soaked in 100mls of warm water 12 hourly) in combination with the conventional therapy (the intervention group) and conventional therapy alone plus 100 ml of plain warm water (the control group).
Drugs administration was given for 28 days. Trained nurses were responsible for the drugs administration, while trained research assistants were responsible for data collection, drug auditing and all other aspects of the study. Study investigators are responsible for ensuring adherence to the study protocol.
Procedure for administration was: put one tea bag in a 100ml cup of water. Soak for eight to10 minutes; allow to cool, and drink warm. Drink 12 hourly.
Control therapy was the conventional therapy for COVID-19 as per the Nigeria NCDC treatment protocol for four weeks, plus 100 ml of warm water given 12 hourly.
All the participants were followed up. During each follow-up weekly visit, participants were assessed for level of compliance and adverse events. In-patients were continually monitored until discharge or death. Follow up monitoring for Adverse Event (AE) eight weeks post discharge.
There was daily monitoring of vital signs: pulse, body weight, blood pressure, body temperature, and oxygen saturation in percentage. The trial also has a NAFDAC clinical trial authorisation certificate.
The product was received on October 8, 2020. 75 persons were screened; 52(26 to each arm) people were recruited and randomised.
Date of first recruitment was January 12, 2021. Date of last recruitment was October 2021.
Number of withdrawals/dropouts is 19. Primary reasons for drop out: traveled out of the State, no longer interested and death.
The presence of premorbid conditions such as hypertension and diabetes mellitus were not different in both the intervention and the control groups.
However, when other co-morbidities such as arthritis, hypercholesterolaemia were added, more participants in the control groups had significantly more pre-morbid conditions.
According to the researchers, only the two participants who had what appeared to be side effects: one patient complained of abdominal pain, which started on Day 11. Pain seemed to occur shortly after taking the tea, however pain persisted even when the tea was discontinued. (Tea was discontinued for three days). Patient took no treatment for abdominal pain, which spontaneously resolved after a few days (Male, 42 years).
Another patient reported frequent stooling with traces of blood of one-day duration on Day 33. Spontaneously resolved (Male, 57 years). Three deaths occurred, in total, among patients in the control arm on days three, seven and nine.
Meanwhile, Kasilo said the objectives of the mission to Nigeria were to: review the country progress in the development of traditional medicine-based therapeutics proposed for COVID-19 treatment; monitor the level of implementation of the WHO recommendations on good clinical practice for evaluating the safety and efficacy of traditional medicine-based therapeutics; identify bottlenecks on the implementation of the WHO/ African Vaccine Regulatory Forum (AVAREF) guidelines on the reviews and decisions on clinical trial approval processes of the products in emergencies; discuss regulatory challenges with the National Regulatory Authorities, National Ethics Committees and National Scientific Committees on COVID-19 and agree on the way forward; advocate for conducting multicenter clinical trials and facilitating collaboration between institutions; identify areas for strengthening of national capacity for development of a plan of action with WHO technical support; document best practices in the conduct of clinical trials of traditional medicine-based therapeutics, lessons learnt and possible solutions to address the challenges encountered and way forward; and develop a statement or press release on the findings of the mission including recommendations in collaboration with the WHO country offices and national authorities which will be released towards the end of the mission.
AVAREF, established by WHO in 2006, is an informal capacity-building platform aimed at improving the regulatory oversight of interventional clinical trials conducted in Africa.
Methodology for the joint mission of Regional Expert Advisory Committee on Traditional Medicine for COVID-19 Response (REACT)/WHO/Africa Centre for Disease Control (CDC) to Nigeria was to hold in-depth discussions with: the researchers and scientific Committees on evaluation of clinical trial preliminary results on the safety, efficacy and quality of traditional medicine-based therapeutics proposed for the treatment of COVID-19; Director-General, National Institute for Pharmaceutical Research and Development (NIPRD) and his collaborators and National Ethics Committee to better understand the challenges related to ethical and regulatory issues in clinical trials initiation and continuation and identify additional bottlenecks which researchers are facing and agree on the way forward.
Others are: to meet with Associations of Traditional Health Practitioners on their contribution to COVID-19 and what role did they play to-date in Nigeria; review the national protocols used for the clinical trials and ensure that they were conducted, recorded, and reported in accordance with the WHO Standard protocols, Standard Operating Procedures (SOPs), Good clinical practice (GCP), and the applicable ethical and regulatory requirements; identify the strengths, weaknesses and areas for improvement of the institutions with a view to strengthening the country capacity in research and development and clinical trial in particular; visit the clinical trial study sites of BDG in Lagos and local manufacturing facilities of traditional medicine-based therapeutics to monitor the implementation of the trials and determine the quality assurance of the herbal medicine product respectively and make recommendations as appropriate; discuss key findings with all stakeholders to ensure alignment and adherence to the national protocol, WHO standard protocol and other international standards; implementation of AVAREF and WHO guidelines on reviews and decisions on clinical trials approval processes for products in emergencies and identify bottlenecks in this regard; identify areas for improvement for the development of a plan of work/Roadmap for strengthening national capacity with WHO technical support; and debrief the WHO Representative, Ministry of Health and other interested parties on the mission and next steps.
Members of the visiting team include: Dr. Yvonne Adu-Boahen, REACT & Director at the Food and Drug Administration (FDA), Ghana and Health of Clinical Trials Department; Dr. Anke Weisheit, REACT and Co-founder PHARM-BRATIC; Prof. Olobayo Kunle, Rapporteur, REACT; Prof. Morenike Upong, REACT and Awolowo University; Prof. Oyewale Tomori; REACT and former WHO staff; Dr. Sangyoung Ahn, Technical Officer, Traditional and Complementary and Integrative Medicine, Traditions Center for Innovation (TCI)/Headquarters (HQ); Dr. Diadie Maiga, Technical Officer, Vaccines Regulation (and other Medical Products); Prof. Ossy M. J. Kasilo, Regional Adviser, Traditional and Complementary and Integrative Medicine, WHO-AFRO; and Prof. Joseph Okeibunor, Team Lead Research, Development and Innovation and Head of the mission, WHO-AFRO.
Indeed, Andrographis paniculata, Garcinia kola seed extract and Psidium guajava leaf extracts as well as some of their major phytochemical constituents have shown validated antiviral, immune-modulatory and adaptogenic activities.
These herbs have long standing ethnomedicinal use and the safety profiles of their major phytoconstituents are well validated and documented.
Andrographolide, the major component of Andrographis, showed in vitro inhibition of the growth of Ebola virus (Zaire) with EC50 activity of 10 μM which is twenty-five-fold the activity of the control Favipiravir (EC50 = 250 μM) in the Crystal violet (Plaque reduction/ Neutral red (Toxicity) assay.
It also showed significant activity against Dengue fever virus with EC50 value of 0.56 μg/ml in the Visual (Cytopathic effect/ Toxicity) Assay and EC50 of 0.58 μg/ml in the Neutral Red (Cytopathic effect/ Toxicity) Assay (comparable to the values obtained with 6-Azauridine as the positive control EC50 = 0.32 μg/ml and 0.38 μg/ml in the respective bioassays.
In a study against SARS Coronavirus, Andrographolide had an EC50 of 1.2 μg/ml in the Visual (cytopathic effect/toxicity) assay and 1.1 μg/ml in the Neutral Red (cytopathic effect/toxicity) assay.
The compound exerts several immune-modulatory properties. In experimental models, it effectively reduces the levels of pro-inflammatory cytokines such as IL-1𝛽, IL-6, GMCSF, and TNF-𝛼.
Extracts of Garcinia kola seed as well as the major phyto-constituent, Kolaviron, and Akiluvir have shown in vitro inhibitory effect against SARS Coronavirus and Ebola virus.
Kolaviron has also shown validated potent immune-modulatory and adaptogenic activities.
Similarly, guava flavonoid glycosides (GFGs) have shown promising activity against influenza A virus and dengue virus. GFGs have also shown potent immune-modulatory activities.
The potent antiviral activities of two of the major active ingredients of the tea namely, Andrographolide and Kolaviron on SARS Coronavirus were recently validated by In vitro studies carried out by the United States National Institute for Health (NIH). This further lends credence to the potential application of IHP Detox Tea in management of SARS Coronavirus pandemic.
Researchers at the Nigerian Institute for Pharmaceutical Research and Development (NIPRD) had discovered NIPRIMUNE, an immune-modulatory phytomedicine, from the plant Andrographis paniculata.
Although the Federal Ministry of Health has refused to invest in clinical trials of the plant since it proved effective against COVID-19, it is on record that Thailand in January 2021 approved Andrographis paniculata for the management of COVID-19 infection. Also, Andrographis paniculata is one of the basic ingredients in Prof. Maurice Iwu’s COVID-19 formulation that is presently going through clinical trials.
Previous studies had shown that A. paniculata is one of the plants used for treating febrile illnesses possibly due to malarial and bacterial infections in local communities in Nigeria. It is locally called Jogbo because of its bitterness but popularly called Mejemeje (seven-seven) among Yoruba speaking natives in Nigeria because an average dosage comprises seven leaves eaten raw once or twice daily for about five days in the treatment of febrile illness or chronic debility and some herbalist also recommend it for treatment of hypertension.
Antibacterial activities of both aqueous and ethanolic leaf extract have been reported. It is a common belief that any bitter leaf is medicinal and must be useful in treating fevers.
Andrographis paniculata is an erect annual herb extremely bitter in taste in all parts of the plant body. The plant is known in northeastern India as “king of bitters”, and belongs to the family Acanthaceae.
The phyto-constituents of Andrographis paniculata plants which has been well elucidated include: diterpenes, flavonoids, iterpenoid, lactones, alkanes, ketones, aldehydes, andrographolides (which is the major constituent), paniculides, farnesols, polyphenols, arabinogalactan, and several other sub-units of andrographolide.
Meanwhile, in late December 2020, the government of Thailand approved a pilot study of the use of the southern Asian herb andrographis (Andrographis paniculata) to treat early symptoms and reduce the severity of COVID-19.
Researchers have established the anti- SARS-CoV-2 activity of Andrographis paniculata extract and its major component Andrographolide in human lung epithelial cells and cytotoxicity evaluation in major organ cell representatives.
In conclusion, the study provided experimental evidence in favour of A. paniculata and andrographolide for further development as a monotherapy or in combination with other effective drugs against SARS-CoV–2 infection.
Iwu told The Guardian: “In one of the published reports, Andrographis has been clinically evaluated about 33 times in full blown clinical trials. A meta-analysis indicated that the trials (when combined) involved 7175 patients in cohorts on the use of A. paniculata for symptomatic relief of acute respiratory tract infections in both children and adults. I will give you the paper to read for yourself.
“You will find that A. paniculata therapy consistently shortened the duration of dry persistent cough, sore throat and sick leave/time to resolution when compared with usual care. The combination of Andrographis paniculata, Garcinia kola and Psidium guajava leaves in the already NAFDAC listed IHP -Detox Tea is an exciting product for the management of this pandemic. Especially as possible pre- and post-exposure prophylaxis as literature on them suggest. Furthermore, the specially ‘cured’ tea has been in human use since 2016 without any reported case of adverse effects. I hope you understand what I mean when I say that the tea is cured.”
Source: The Guardian
