Study: Amla tea in hospitalized patients with COVID-19

reference

Varnasseri M, Siahpoosh A, Hoseinynejad K, et al. The effects of additional therapy ofPhyllanthus emblica(amla) on laboratory-confirmed COVID-19 cases: a randomized, double-blind, controlled trial.Supplement Ther Med. 2022;65:102808.

Study objective

To evaluate whether the addition ofPhyllanthus emblica(Amla) tea according to standard protocols affects lung function, symptomology and length of hospital stay in a population of hospitalized patients with Covid-19

Key to take away

While amla tea did not reduce the severity of lung involvement or significantly affect reverse transcription-polymerase chain reaction (RT-PCR) results, it did reduce symptom severity and C-reactive protein (CRP) levels. The length of hospital stay was significantly shorter for those who took Amla compared to placebo.

design

Randomized, double-blind, placebo-controlled trial

Participant

Investigators recruited a total of 61 hospitalized patients aged 18 years with symptoms of Covid-19 (RT-PCR positive) from May 1, 2020 to June 1, 2020 in Razi and Sina Hospitals, Ahvaz, Iran. At the end of the study, they analyzed 60 patients.

There was no significant difference between arms (n=30 on placebo, n=30 on intervention) in age, height, weight, body mass index (BMI), gender, marital status, education, occupation, living environment, pulmonary disease history, treatment history and comorbidities.

Inclusion criteria

18 years or older, positive RT-PCR for COVID-19, lung involvement on chest imaging, hospitalization with fever>38°C (oral or axillary) or respiratory rate >24 breaths/minute or cough within 8 days of illness onset.

Exclusion criteria

Disapproval from doctors, liver disease, advanced kidney disease, allergy to procedures, pregnancy, breastfeeding, transfer to a non-destination hospital within 72 hours, on trial for Covid-19 in the last 30 days, history of taking an angiotensin converting enzyme (ACE) inhibitor, WHO severity code >6 for Covid-19 and not signing the consent form.

intervention

First-line therapy for all patients consisted of hydroxychloroquine tablets (200 mg) and lopinavir/ritonavir (Kaletra) every 12 hours after meals for 7 to 14 days.Phyllanthus emblica(Linn), Euphorbiaceae, known as Indian gooseberry or Amla orEmblica officinalis, 2 grams of powder in a sachet for 10 days was the intervention, and the placebo was starch, 2 grams of powder daily for 10 days. Both treatments were taken as 100 ml tea every 12 hours. Hospital nurses delivered treatments every 12 hours for 10 days, and the study team monitored patients through daily phone calls.

The team purchased dried fruits from a pharmaceutical plant store in April 2020, identified them and placed a sample in the herbarium of the Department of Pharmacognosy, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran. The Pharmacognosy Department prepared intervention and placebo sachets that look and taste the same.Phyllanthus emblicaThe polyphenol content was 39.56 grams of gallic acid per 100 grams.

Evaluated study parameters

Objective parameters assessed included oxygen saturation (SpO ).₂), computed tomography (CT) findings, RT-PCR for SARS-CoV2, lymphocytes, hemoglobin, polymorphonucleocytes (PMNs), platelets, erythrocyte sedimentation rate (ESR), and CRP. Continuous variables included fever and respiratory rate. Symptoms included myalgia, sore throat, shortness of breath, and weakness. Length of hospital stay (LOS) was also recorded.

Primary outcome

The primary outcome was a change in RT-PCR results between the first and last day (Day 10) of the study intervention.

Key findings

There was no difference in oxygen consumption or lung involvement between the two arms; Both arms had a significant increase in oxygen levels (P<0.001) and a significant reduction in lung involvement as assessed by CT scans (P<0.001) at the end of the study.

Further findings include:

• Im Interventionsarm nahmen die Lymphozyten signifikant ab (P=0,031), stieg aber im Querlenker deutlich an (P=0,001).
• Es gab keinen signifikanten Unterschied in Bezug auf Hämoglobin, polymorphkernige (PMN) Anzahl, Blutplättchen oder Erythrozytensedimentationsrate (ESR) zwischen den Interventions- und Placeboarmen.
• CRP war in der Interventionsgruppe im Vergleich zur Kontrollgruppe signifikant niedriger (P=0,004).
• Das Fieber ging in beiden Armen zurück, wobei der Rückgang im Interventionsarm deutlich stärker ausfiel (P<0,001).
• Schüttelfrost, Halsschmerzen und Schwäche nahmen in beiden Armen deutlich ab.
• Die Schwere des Hustens war in beiden Fällen geringer, fiel jedoch deutlich geringer aus als im Kontrollarm (P<0,001).
• Myalgie nahm in beiden Gruppen signifikant ab (P<0,001), mit einer deutlicheren Reduzierung im Interventionsarm (P=0,005).
• Die Krankenhausaufenthaltsdauer war im Interventionsarm (4,44 Tage) im Vergleich zum Kontrollarm (7,18 Tage) signifikant kürzer; P<0,001).

There were no side effects in either arm.

transparency

The authors stated that they had no competing interests and all contributed equally.

Effects on practice

Phyllanthus emblicaAlso known as Indian gooseberry or amla because of its fruit, it is known in Buddhism as the small tree under which the 21st century lives^stBuddha found enlightenment. The fruits are eaten raw or cooked; the inner bark is used in Sumatra, Indonesia, as an astringent or bittering agent in fish dishes; and the dried fruits are used in Ayurvedic medicine.¹The fruit contains ascorbic acid, ellagitannins (emblicanin A and B, punigluconin, pedunculagin), punicafolin, phyllanemblinin A, phyllemblin, polyphenols, flavonoids, kaempferol, ellagic acid and gallic acid.¹

Traditional uses include immunomodulation in degenerative processes, digestion, constipation, fever regulation, cough, asthma, heart problems, vision, hair growth and intellectual functions.¹In mice with Dalton lymphoma ascitesP Emblicaincreased natural killer cell activity, antibody-dependent cellular cytotoxicity, and lifespan by 35%.¹In mice,P Emblicaprevented bacterial colonizationKlebsiella pneumoniaeWhen administered for 30 instead of 15 days, there was reduced malondialdehyde, increased phagocytic activity and increased nitrate content in the bronchioalveolar lavage fluids.

P EmblicaProvides hepatoprotective effects against ethanol, paracetamol, carbon tetrachloride, heavy metals, ochratoxins, hexachlorocyclohexane and antitubercular drugs.²It has also been shown to be beneficial in hyperlipidemia, metabolic syndrome, hepatocarcinogenesis and hepatotoxicity caused by iron overload.²It protects against microcystins, galactosamine and lipopolysaccharides.²

Traditional uses include immunomodulation in degenerative processes, digestion, constipation, fever regulation, cough, asthma, heart problems, vision, hair growth and intellectual functions.

P Emblicais effective against bacteria, especially gram-positive ones; viruses; and some mushrooms.³It can inhibit herpes simplex virus 1 (HSV-1) and HSV-2 due to the phenolic content and Coxsackie virus due to the phyllaemblicin B from the roots.³It reduced markers of oxidative stress in patients with end-stage renal disease and uremia.³

In a 28-day human study in hypercholesterolemic men with and without type 2 diabetes (T2D), doses of 2 to 3 g/day of powdered fruit reduced total cholesterol, low-density lipoproteins (LDL), and triglycerides and improved high-density lipoproteins (HDL) by 21 days.³In adults with a BMI of 25 to 35 who were not receiving statin therapy, LDL was significantly reduced (P<0.023) and the total cholesterol/HDL ratio decreased (P<0.006) after 12 weeks using a standardized extract of 500 mg twice daily.³

The viral enzyme 3-chymotrypsin-cysteine ​​protease (3CL) controls the replication of the coronavirus, is essential for its life cycle and is involved in the replication of both SARS-CoV2 and MERS-CoV.⁴In this study, researchers examined a medicinal plant library containing 32,297 botanicals. Potential candidates include:Psorothamnus arborescens, Myrica cerifera, Hyptis atrorubens poit, Phaseolus vulgaris, Phyllanthus emblica, Fraxinus sieboldiana, Camellia sinensis, Glycyrrhiza uralensis,AndAmaranthus tricolor.⁴The identified compound inP Emblicawas 25-eriodictyol 7-O(6'-O-galloyl) beta-D-glucopyranoside.⁴In one (nin vitroStudy of HSV-1 and HSV-2, 1246TGG (1,2,4,6-Tetra-O-galloyl-beta-D-glucose) inactivated HSV-1 particles, resulting in infection failure, virus attachment failure and virus penetration failure.⁴This compound also suppressed intracellular growth from 0 to 12 hours postinfection, with best benefit at 3 hours postinfection and a reduction in viral protein synthesis in host cells.⁴

An attempt byP EmblicaDried fruits administered orally in awake cats and receiving mechanical stimulation of the laryngopharyngeal and tracheobronchial mucosa of the respiratory tract showed significant cough suppressant effects.⁵At 50 mg/kg there was a benefit, and at 200 mg/kg there was an even greater effect on the number of coughing efforts, the frequency of coughing, and the intensity of the cough when inhaling and exhaling.⁵The effect ofP Emblicawas dose-dependent and less effective than codeine but more effective than dropropizine, suggesting anti-inflammatory, antispasmodic and antioxidant effects of the dried fruits.⁵

Summary

In this randomized, double-blind, controlled trial of 61 hospitalized Iranian patients with RT-PCR positive for Covid-19,Phyllanthus emblicaAs a 2 g tea twice daily, lymphocytes, CRP, fever, cough, shortness of breath, myalgia, and length of hospital stay significantly decreased without any adverse effects.Phyllanthus Emblicajoins the ranksAndrographis paniculata, Glycyrrhiza glabra, Azadirachta indica,other plant species, fungi and various plant components, as well as honey with potential anti-Covid-19 activity.^6-9