Table 1 Study characteristics
Author(s), year Study Design Country ROB2Â [62]Â Score | Participants | Intervention/Control Groups | Outcome Measures | Key Results |
|---|---|---|---|---|
Biswas et al. 2014 [50] Randomized, double-blind placebo-controlled pilot study Kolkata, India High Risk of Bias | Population: Adult smokers (n = 30 total) Sex: 30 Males Age: 20–60 years Characteristics: chronic cough, poor immune status, compromised cardiovascular status, and lipid profile | Intervention: n = 20, 250 mg aqueous EO fruit extract (standardized to contain ≥ 60% w/w low molecular weight hydrolysable tannins) capsule b.i.d. PO for 60 days Control: n = 10, 250 mg placebo (microcrystalline cellulose, lactose and magnesium stearate) capsule b.i.d. PO for 60 days | TC, LDL-C, HDL-C, TG, hsCRP | Significant decrease in TC, LDL-C, TC/HDL-C ratio, LDL-C/HDL-C ratio, hsCRP, and significant increase in HDL-C after EO compared with baseline |
Fatima et al. 2014 [51] Randomized, double-blind, placebo-controlled crossover study Hyderabad, India Some Concern of Bias | Population: Healthy adults (n = 12 total) Sex: 12 males Age: 20–30 years, mean of 25.62 ± 2.32 years Characteristics: mean BMI 22.42 ± 2.32 kg/m2) | Intervention: n = 12, 250 mg aqueous EO fruit extract (standardized to contain ≥ 60% w/w low molecular weight hydrolysable tannins) capsule b.i.d. PO for 14 days 14-day washout period Control: n = 12, placebo capsule contains microcrystalline cellulose (49.7% w/w), lactose (49.5% w/w) and magnesium stearate (0.69% w/w) b.i.d. PO for 14 days | Automated, radial and aortic SBP and DBP using non-invasive software (SphygmoCor; AtCor Medical, Australia) | Significant decrease in cold pressor stress test induced changes on aortic wave reflections after EO compared with baseline and placebo |
Ghaffari et al. 2020 [52] Randomized, triple-blind, placebo-controlled add-on clinical trial Tabriz, Iran Some Concern of Bias | Population: Adults with uncontrolled hypertension (n = 81 total) Sex: 45 males, 36 females Age: 35–74 years, mean of 53.64 ± 10.01 years Characteristics: BMI < 30, SBP ≥ 140 mm Hg, DBP ≥ 90 mm Hg or both, and SBP ≥ 150 mm Hg for patients older than 60 years), maximum of 2 antihypertensive drugs for at least 8 weeks, a minimum of one month must have elapsed from the start of medication | Intervention: n = 41, 500 mg EO fruit powder (fresh EO fruit dried then powdered) capsule t.i.d. PO after meal for 8 weeks Control: n = 40, placebo (wheat starch powder) capsule t.i.d. PO after meal for 8 weeks | Automated, brachial SBP and DBP TC, LDL-C, HDL-C, TG | Significant decrease in SBP and DBP after EO compared with baseline and control group |
Kapoor et al. 2020 [53] Randomized, double-blind, placebo-controlled crossover study Japan Some Concern of Bias | Population: Healthy adults (n = 13 total) Sex: 6 males, 7 females Age: 36–67 years, mean of 51.9 ± 2.8 years Characteristics: Mean BMI 25.1 ± 0.63 kg/m2, with elevated TG, lower HDL-C, and average blood fluidity | Intervention: n = 13, 125 mg aqueous EO fruit extract powder (EO fruit pulp hydrolysed with pectinase followed by centrifugation with the supernatant spray dried) capsule q.i.d. PO (2 capsules after breakfast + 2 after dinner) for 4 weeks (each capsule contained 125 mg EO + 125 mg dextrin) 3-week washout period Control: n = 13, 250 mg dextrin capsule q.i.d. PO (2 capsules after breakfast + 2 after dinner every day) for 4 weeks | Automated, brachial SBP and DBP TC, LDL-C, HDL-C, TG | Significant increase in HDL-C after 2 weeks (but not 4 weeks) of EO compared with baseline |
Shanmugarajan et al. 2021 [54] Randomized, double-blind, placebo-controlled clinical trial Puducherry, India Some Concern of Bias | Population: Adults with essential hypertension (n = 150 total) Sex: 119 males, 31 females Age: Intervention: mean of 58.8 ± 8.68 years, control: mean of 60.0 ± 9.42 years Characteristics: Essential hypertension on amlodipine 5 mg or enalapril 5 mg and had not yet attained target blood pressure goals (130 mmHg of systolic and 80 mmHg of diastolic blood pressure) | Intervention: n = 75, 500 mg aqueous EO dried fruit extract powder capsule b.i.d. PO for 12 weeks Control: n = 75, 500 mg maize starch IP grade capsule b.i.d. PO for 12 weeks | SBP, DBP TC, LDL-C, VLDL-C, HDL-C, TG, hsCRP | NS change in SBP, DBP, TC, LDL-C, VLDL-C, HDL-C, TG, or hsCRP after EO compared with placebo |
Upadya et al. 2019 [55] Randomized, double-blind, placebo-controlled, multicenter clinical trial Southern India Some Concern of Bias | Population: Adults with dyslipidemia (n = 98 total) Sex: 45 males, 53 females Age: 30–65 years, intervention: mean of 40.7 ± 10.13 years, control: mean of 42.2 ± 9.20 years Characteristics: TG > 200 mg/dL, LDL-C > 130 mg/dL, TC > 200 mg/dL and HDL-C < 40 mg/dL for men and < 50 mg/dL for women Patients were not taking any medication (including herbal product) for management of dyslipidemia in past 4 weeks | Intervention: n = 49, 500 mg aqueous EO fruit extract powder (fresh, whole EO fruit extracted with ethyl acetate, standardized to contain ≥ 35% polyphenols, 8% triterpenoids, and 10% EO oil) capsule b.i.d. PO (1 capsule after breakfast + 1 after dinner) for 12 weeks Control: n = 49, 500 mg roasted rice powder capsule b.i.d. PO (1 capsule after breakfast + 1 after dinner) for 12 weeks | TC, LDL-C, VLDL-C, HDL-C, TG, hsCRP | Significant decrease in TC, LDL-C, VLDL-C, and TG after EO compared with placebo |
Usharani et al. 2013 [56] Randomized, double-blind, placebo-controlled study Hyderabad, India Some Concern of Bias | Population: Adults with T2DM (n = 80 total) Sex: 53 males, 27 females Age: 30–68 years, intervention 1: mean of 57.60 ± 9.67 years, intervention 2: mean of 57.75 ± 9.86 years, intervention 3: mean of 56.95 ± 8.04 years, control: mean of 56.90 ± 9.17 years Characteristics: Fasting blood glucose of 110–126 mg/dL, glycosylated hemoglobin of 7%–9%, on stable antidiabetic medication (metformin 1,500–3,000 mg) for the 8 weeks prior to the screening visit, and endothelial dysfunction | Intervention 1: n = 20, 250 mg aqueous EO extract (standardized to contain ≥ 60% w/w low molecular weight hydrolysable tannins) capsule b.i.d. PO for 12 weeks Intervention 2: n = 20, 500 mg aqueous EO extract capsule b.i.d. PO for 12 weeks Intervention 3: n = 20, 10 mg atorvastatin capsule o.d. PO at bedtime + matching placebo capsule o.d. PO in the morning for 12 weeks Control: n = 20, placebo capsule b.i.d. PO for 12 weeks. Matching placebo capsules contained microcrystalline cellulose (49.7% w/w), lactose (49.5% w/w), and magnesium stearate (0.69% w/w) as excipients | TC, LDL-C, VLDL-C, HDL-C, TG, hsCRP | Significant decrease in TC, LDL-C, TG, hsCRP and significant increase in HDL-C after both EO dosages and atorvastatin compared with baseline and placebo Significant decrease in VLDL-C after both EO dosages compared with baseline but not placebo Significant decrease in VLDL-C after atorvastatin compared with baseline and placebo |
Usharani et al. 2019 [57] Prospective, randomised, double-blind and placebo-controlled clinical study Hyderabad, India Some Concern of Bias | Population: Adults with metabolic syndrome (n = 59 total) Sex: 43 males, 16 females Age: 30–68 years, intervention 1: mean of 57.45 ± 7.44 years, intervention 2: mean of 57.24 ± 8.94 years, control: mean of 56.89 ± 7.39 years Characteristics: Endothelial dysfunction | Intervention 1: n = 20, 250 mg aqueous EO fruit extract (standardized to contain ≥ 60% w/w low molecular weight hydrolysable tannins) capsule b.i.d. PO for 12 weeks Intervention 2: n = 21, 500 mg aqueous EO fruit extract capsule b.i.d. PO for 12 weeks Control: n = 18, placebo (microcrystalline cellulose, lactose and magnesium stearate) capsule b.i.d. PO for 12 weeks | TC, LDL-C, HDL-C, TG, hsCRP | Significant decrease in TC, LDL-C, HDL-C, TG, and hsCRP after both EO dosages compared with baseline and placebo |
Usharani et al. 2017 [58] Randomized, double-blind, placebo-controlled, crossover study Hyderabad, India Some Concern of Bias | Population: Healthy adults (n = 12 total) Sex: 12 males Age: 20–30 years, mean of 24.75 ± 2.01 years Characteristics: BMI between 18–24.9 kg/m2 and non-smokers | Intervention: n = 12, 250 mg aqueous EO fruit extract (standardized to contain ≥ 60% w/w low molecular weight hydrolysable tannins) capsule q.i.d. PO (2 capsules b.i.d. PO) for 14 days 14-day washout period Control: n = 12, 250 mg placebo (microcrystalline cellulose, croscarmellose sodium, silicon dioxide, talc and magnesium stearate) capsule q.i.d. PO (2 capsules b.i.d. PO) for 14 days | Automated, radial and aortic SBP and DBP using non-invasive software (SphygmoCor; AtCor Medical, Australia) | Significant decrease in mental stress test induced changes on aortic wave reflections after EO compared with baseline and placebo |