Reference
Varnasseri M, Siahpoosh A, Hoseinynejad K, et al. The effects of add-on therapy of Phyllanthus emblica (amla) on laboratory confirmed COVID-19 cases: a randomized, double-blind, controlled trial. Complement Ther Med. 2022;65:102808.
Study Objective
To evaluate whether the addition of Phyllanthus emblica (amla) tea to standard protocols affects lung function, symptomology, and length of hospital stay in a population of hospitalized patients with Covid-19
Key Takeaway
While amla tea did not reduce the severity of lung involvement nor significantly affect the reverse transcription–polymerase chain reaction (RT-PCR) results, it did lessen severity of symptomology and C-reactive protein (CRP) levels. Duration of hospital stay was significantly shorterin those taking amla versus placebo.
Design
Randomized, double-blind, placebo-controlled trial
Participants
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, at Razi and Sina Hospitals, Ahvaz, Iran. They analyzed 60 patients at the study end.
Between the arms (n=30 in placebo, n=30 in intervention), there was no significant difference in age, height, weight, body mass index (BMI), gender, marital status, education, occupation, living setting, pulmonary disease history, history of treatments, and comorbidities.
Inclusion Criteria
Aged 18 years or more, positive RT-PCR for COVID-19, pulmonary involvement on chest imaging, hospitalized with fever >38 C° (oral or axillary,) or respiratory rate >24 breaths/minute, or cough within 8 days of disease onset.
Exclusion Criteria
Disapproval by physicians, liver disease, advanced kidney disease, allergy to intervention, pregnancy, lactation, transfer to a nontarget hospital within 72 hours, in a trial for Covid-19 in the past 30 days, history of taking an angiotensin-converting-enzyme (ACE)-inhibitor, WHO severity code >6 for Covid-19, and not signing 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 or Emblica 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 administered the treatments every 12 hours for 10 days, and the study team tracked the patients with daily phone calls.
The team purchased dried fruit from a pharmaceutical plant store in April 2020, identified it, and placed a specimen in the herbarium at the Department of Pharmacognosy, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran. The Department of Pharmacognosy prepared intervention and placebo sachets to look and taste the same. Phyllanthus emblica polyphenol content was 39.56 grams gallic acid per 100 grams.
Study Parameters Assessed
The objective parameters assessed included oxygen saturation (SpO2), computerized 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 the final day (day 10) of the study intervention.
Key Findings
There was no difference in oxygen usage or lung involvement between the 2 arms; both arms had a significant increase in oxygen (P<0.001) and a significant decrease in lung involvement as determined by CT scans (P<0.001) at the end of the study.
Other findings include:
- Lymphocytes decreased significantly in the intervention arm (P=0.031) but increased significantly in the control arm (P=0.001).
- There was no significant difference in hemoglobin, polymorphonuclear (PMN) count, platelets, or erythrocyte sedimentation rate (ESR) between the intervention versus placebo arms.
- CRP was significantly less in the intervention group versus the control (P=0.004).
- Fever decreased in both arms, with a significantly greater reduction in the intervention arm (P<0.001).
- Chills, sore throat, and weakness decreased significantly in both arms.
- Cough severity was reduced in both but became significantly less than in the control arm (P<0.001).
- Myalgia decreased significantly in both groups (P<0.001), with a more significant reduction in the intervention arm (P=0.005).
- Hospital length of stay was significantly shorter in the intervention arm (4.44 days) compared to the control arm (7.18 days; P<0.001).
No adverse effects occurred in either arm.
Transparency
The authors declared no competing interests, and all contributed equally.
Practice Implications
Phyllanthus emblica, known as Indian gooseberry for its fruit, or amla, is famous in Buddhism as the small tree under which the 21st Buddha found enlightenment. The fruit is eaten raw or cooked; the inner bark is used in Sumatra, Indonesia, as an astringent or bitter in fish dishes; and the dried fruit is used in Ayurvedic medicine.1 The 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 immune modulation for degenerative processes, digestion, constipation, fever regulation, cough, asthma, heart conditions, vision, hair growth, and intellectual function.1 In mice with Dalton’s lymphoma ascites, P emblica enhanced natural killer cell activity, antibody-dependent cellular cytotoxicity, and life span by 35%.1 In mice, P emblica prevented bacterial colonization by Klebsiella pneumoniae when given for 30 days rather than 15 days, decreased malondialdehyde, increased phagocytic activity, and increased nitrate levels in bronchioalveolar lavage fluids.
P emblica provides hepatoprotective effects against ethanol, acetaminophen, carbon tetrachloride, heavy metals, ochratoxins, hexachlorocyclohexane, and antitubercular medications.2 It has also been found beneficial in hyperlipidemia, metabolic syndrome, hepatocarcinogenesis, and hepatotoxicity from iron overload.2 It is protective against microcystins, galactosamine, and lipopolysaccharides.2
Traditional uses include immune modulation for degenerative processes, digestion, constipation, fever regulation, cough, asthma, heart conditions, vision, hair growth, and intellectual function.
P emblica is effective against bacteria, especially gram-positive; viruses; and some fungi.3 It can inhibit herpes simplex virus 1 (HSV-1) and HSV-2 due to phenolic content, and coxsackie virus due to phyllaemblicin B from the roots.3 In patients with end-stage renal disease with uremia, it reduced markers of oxidative stress.3
Doses in a human trial over 28 days with hypercholesteremic men, with and without type 2 diabetes (T2D), 2 to 3 g/d of powdered fruit decreased total cholesterol, low-density lipoproteins (LDL), and triglycerides, and improved high-density lipoproteins (HDL) by 21 days.3 In adults with a BMI of 25 to 35 not on statin therapy, LDL was decreased significantly (P<0.023), and total cholesterol/HDL ratio decreased (P<0.006) at 12 weeks using a standardized extract of 500 mg twice daily.3
The virus 3-chymotrypsin-cysteine protease (3CL) enzyme controls coronavirus replication, is essential for its life cycle, and is involved in both SARS-CoV2 and MERS-CoV replication.4 In this study investigators screened a medicinal plant library of 32,297 plant compounds. Potential candidates include Psorothamnus arborescens, Myrica cerifera, Hyptis atrorubens poit, Phaseolus vulgaris, Phyllanthus emblica, Fraxinus sieboldiana, Camellia sinensis, Glycyrrhiza uralensis, and Amaranthus tricolor.4 The identified compound in P emblica was 25-eriodictyol 7-O(6’-O-galloyl) beta-D-glucopyranoside.4 In an in vitro study of HSV-1 and HSV-2, 1246TGG (1,2,4,6-tetra-O-galloyl-beta-D-glucose) inactivated HSV-1 particles, leading to infection failure, viral attachment failure, and viral penetration failure.4 This compound also suppressed intracellular growth 0 to 12 hours postinfection, with the best benefit at 3 hours postinfection and a reduction in viral protein synthesis in host cells.4
A trial of P emblica dried fruit given orally in conscious cats receiving mechanical stimulation of the laryngopharyngeal and tracheobronchial mucous airways showed distinct cough suppressive effects.5 At 50 mg/kg there was benefit, and at 200 mg/kg there was even greater effect on number of cough efforts, frequency of cough, and intensity of cough on inspiration and expiration.5 The effect of P emblica was dose-dependent and less effective than codeine, but more effective than dropropizine, suggesting antiphlogistic, antispasmolytic, and antioxidant effects from the dried fruit.5
Summary
In this randomized, double-blind, controlled trial of 61 hospitalized Iranian patients RT-PCR positive for Covid-19, Phyllanthus emblica as a 2-g tea twice daily significantly decreased lymphocytes, CRP, fever, cough, shortness of breath, myalgia, and length of hospital stay without adverse effects. Phyllanthus emblica joins the ranks of Andrographis paniculata, Glycyrrhiza glabra, Azadirachta indica, other plant species, mushrooms, and diverse plant constituents as well as honey with potential anti-Covid-19 activity.6-9
