Author, year [ref.] Study design Recruited sample size, n (analysed sample size, n ) Sample description (age; gender; comorbidities) Indication for C. papaya leaf Intervention details (formulation; dose; frequency; duration) Comparator/cointervention Safety data reported (yes/no) Adverse reactions (number, n , OR percentage patient in analysed population, %) Hettige, 2008 [32 ] Case series 12 (12) 5–44 y; 50% M, 50% F; NS Dengue Fresh C. papaya leaf juice; 2.5–5 mL; 2 doses 8 hours apart NA/ Routine dengue supportive treatment except steroids, blood products, and nonsteroidal anti-inflammatory drugs Yes Rash (n = 5) Ahmad, 2011 [33 ] Case report 1 (1) 45 y; M; NS Dengue (diagnosed based on signs and symptoms and risk factors, without a serology test) Fresh C. papaya leaf juice; 25 mL; Twice daily; 5 days NA/ Broad-spectrum antibiotics and antimalarial drugs No — Assir, 2012 [34 ] RCT 39 (NS) Adult (age NS); 72% M, 28% F; NS Dengue CPLE syrup; 5 mL; Twice daily; 5 days Placebo/ NS Yes No significant adverse event occurred in either group Kala, 2012 [35 ] Case series 5 (5) 19–52 y; NS; NS Dengue (diagnosed based on signs and symptoms and risk factors, without a serology test) Fresh C. papaya leaf juice; 30 mL; 3 times daily; NS (but the observation duration was 2 days) NA/ Not mentioned No — Yunita, 2012 [36 ] RCT 80 (80) 15–34 y; 56% M, 44% F; NS Dengue C. papaya leaf 70% ethanolic extract in capsule; 1100 mg; 3 times daily; 5 daysControl group without placebo/routine dengue supportive treatment No — Subenthiran, 2013 [6 ] RCT 290 (228) Mean 28.4 y ± SD 8.8; 85% M, 15% F; None Dengue Fresh C. papaya leaf juice; 50 g leaves; Once daily; 3 days Control group without placebo/routine dengue supportive treatment No — Gowda, 2014 [37 ] RCT 30 (30) 18–55 y; 73% M, 27% F; NS Dengue CPLE tablet (Caripill, Microlabs); 1100 mg; 3 times daily; 5 days Control group without placebo/routine dengue supportive treatment Yes Gastrointestinal disturbances, e.g., nausea and vomiting which were similar across groups Siddique, 2014 [38 ] Case report 1 (1) 23 y; M; None Dengue Fresh C. papaya leaf juice; 150 mL (1 and a half leaf); Once daily; 5 days NA/ Commercial fruit juices (NS) No — Abhishek, 2015 [39 ] RCT 60 (60) 18–55 y; 73% M, 27% F; NS Dengue CPLE tablet; 1100 mg; 3 times daily; 5 days Control group without placebo/Routine dengue supportive treatment Yes Gastrointestinal disturbances, e.g., nausea and vomiting which were similar across groups Gadhwal, 2016 [40 ] RCT 400 (400) >16 y; 69% M, 31% F; NS Dengue Dried C. papaya leaf crude aqueous extract in capsule; 500 mg; Once daily; 5 days Control group without placebo/routine dengue supportive treatment (antipyretic paracetamol, intravenous 0.9% normal saline, antiemetic) Yes None Kasture, 2016 [41 ] RCT 300 (292) 18–55 y; 55% M, 45% F; NS Dengue CPLE tablet (Caripill, Microlabs); 1100 mg; 3 times daily; 5 days Placebo/ Routine dengue supportive treatment except corticosteroids Yes Nausea (n = 26) and vomiting (n = 17) which were evenly distributed across groups Rash (n = 9) in the intervention group Singhai, 2016 [42 ] RCT 80 (NS) >18 y; NS; NS Febrile thrombocytopaenia CPLE capsule; 2 capsules (strength NS); 3 times daily; 9 days NS/none reported No — Adarsh, 2017 [43 ] RCT 100 (100) 21–65 y: 45% M, 55% F; NS Dengue CPLE capsule; 500 mg; 3 times daily; 5 days Placebo/ Routine dengue supportive treatment (intravenous fluids, paracetamol, antacids, platelet transfusion, and inotropic agents) Yes No severe adverse events; Gastrointestinal disturbances, e.g., nausea and vomiting reported in both treatment and control groups Hussain, 2017 [44 ] Quasiexperimental trial 60 (58) 28–80 y; 66% M, 34% F; Malignancy, ischaemic heart disease, chronic obstructive pulmonary disease, diabetes, and others (NS) CIT Fresh papaya leaf granules in capsule; 290 mg; Twice daily; 5 days Control group without placebo/ Chemotherapy, single or in combination of 5-fluorouracil, bleomycin, etoposide, ifosfamide, cyclophosphamide, paclitaxel, docetaxel, carboplatin, oxaliplatin, gemcitabine, capecitabine, and cisplatin with radiation Yes None; No significant changes in haematological and biochemical (NS) values; No treatment-related deaths Sundarmurthy, 2017 [5 ] RCT 40 (40) Mean 42.5 y ± SD 10.2; 62.5% M, 37.5% F; Solid tumour malignancy and others (NS) CIT CPLE tablet (marketed product, brand (NS)); 1100 mg; 3 times daily; 7 days Control group without placebo/NS Yes Diarrhea (15%), dizziness (10%), vomiting (15%), headache (10%), and dysgeusia (20%) the in intervention group; Comparable to the control group Rahmat, 2018 [45 ] Case report 1 (1) 76 y; M; Prostate cancer, hypertension, IgG2/IgG4 subclass deficiency Prostate cancer CPLE tea and elixir; 4 g tea, 5 mL elixir; Twice daily (morning tea, night elixir); NS NA/ None reported, though having a strong history of using natural products Yes None Hampilos, 2019 [46 ] Case series 4 (4) 21–67 y; 50% M, 50% F; Chronic immune thrombocytopaenic purpura, hyperlipidaemia, hypothyroidism, and ulcerative colitis Chronic immune thrombocytopaenic purpura C. papaya leaf 10:1 glycerin extract (in liquid and capsule); 600 mg–1200 mg; 3 times daily; Up to ten monthsNA/ Steroids (prednisolone), gemfibrozil, and levothyroxine Yes Increased glucose levels (n = 1); lymphopaenia (n = 1) ; Increased appetite (n = 1) Pandita, 2019 [47 ] Case report 1 (1) Neonate (30 weeks preterm 23 days of life); M; None Sepsis thrombocytopaenia CPLE syrup (Caripill, Microlabs); 20 mg/kg; 3 times daily; 19 days (tapered off) NA/ Hospital resuscitative support Yes None; Baby healthy up to 18 months of age at follow-up Srikanth, 2019 [48 ] RCT 294 (285) Mean 7.75 y ± SD 3.27; 50% M, 50% F; NS Dengue CPLE syrup (Caripill, Microlabs); 275–550 mg; 3 times daily; 5 days Control group without placebo/ Routine dengue supportive treatment Yes Nausea (n = 2) in the intervention group Sathyapalan, 2020 [49 ] RCT 50 (50) Mean 52.5 y ± SD 15; 61% M, 39% F; NS Dengue CPLE tablet (Caripill, Microlabs); 1100 mg; 3 times daily; 5 days Placebo/ Routine dengue supportive treatment Yes No serious adverse events reported up to 2 weeks after intervention cessation Sreelatha, 2020 [50 ] Single-arm retrospective audit 50 (50) 19–75 y; 50% M, 50% F; Solid tumour malignancy and others (NS) CIT CPLE tablet; 1100 mg; 3 times daily; Up to 2 weeks NA/temozolomide, paclitaxel, docetaxel, gemcitabine, doxorubicin, cyclophosphamide, rituximab, vincristine, 5-fluorouracil, cisplatin, carboplatin, oxaliplatin, and capecitabine Yes Dysgeusia and nausea