Olive Leaf Extract

Background: Olive leaves, a by-product of olive oil production, are rich in oleuropein, a phenolic compound with antioxidant and anti-inflammatory properties. This systematic review and meta-analysis evaluated the effects of olive leaf extract (OLE) and oleuropein on glucose metabolism, lipid profile, and inflammatory markers in randomized clinical trials (RCTs). Methods: The review was registered in PROSPERO (CRD42022375615) and followed PRISMA guidelines. PubMed, Scopus, and Web of Science were searched up to January 2026 without restrictions. Eligible studies were RCTs in adults comparing OLE or oleuropein with placebo or control. Study selection, data extraction, and risk of bias (RoB 2) assessment were performed independently by two reviewers; certainty of evidence was assessed with GRADE. Meta-analyses were conducted when at least two trials reported suitable data. Results: Eleven RCTs were included (4 short-term and 7 continuous-intake trials). Short-term crossover studies showed heterogeneous effects on postprandial glycemia and insulin responses, precluding meta-analysis. In continuous-intake, parallel-design RCTs, pooled analyses demonstrated no statistically or clinically significant effects on glycemic or lipid outcomes. Evidence regarding inflammatory markers was scarce and of low certainty. Conclusion: The current evidence does not support clinical recommendations for OLE supplementation aimed at health benefits. Data from methodologically consistent and robust trials indicate no statistically significant metabolic or inflammatory effects under usual human consumption patterns, whereas evidence from other study designs remains inconclusive. Further high-quality RCTs are required to clarify potential metabolic benefits.

BACKGROUND: Treatments for Gastroesophageal Reflux Disease (GERD) symptoms include pharmaceutical, surgical, dietary, and lifestyle behaviors; however, dietary interventions lack evidence synthesis. RESEARCH QUESTION: What is the effect of dietary, probiotic, and nutraceutical interventions on GERD symptoms, with or without pharmaceutical therapy, in adults with a history of GERD or functional dyspepsia compared to no intervention, placebo, or usual care? METHOD: A systematic review and meta-analysis was performed according to PRISMA. The search strategy was implemented in MEDLINE, CINAHL, CENTRAL, and Embase on the 28th October 2020 and updated to 27th July 2021. Intervention studies were eligible if they evaluated the effect of a dietary, nutraceutical, or probiotic intervention on GERD symptoms in adults with a history of GERD or functional dyspepsia. The internal validity of studies was assessed using the Academy Quality Criteria Checklist; Review Manager software was used to perform meta-analysis; and certainty in the body of evidence was assessed using GRADE. RESULTS: 6,608 study records were retrieved from the search, with 21 studies (n = 24 highly heterogenous intervention groups) included (n = 10 restrictive dietary interventions; n = 3 non-restrictive dietary interventions; n = 8 nutraceutical interventions; and n = 3 probiotic interventions). GERD symptoms were clinically and statistically improved by a test-based elimination diet (n = 1 study), low nickel diet (n = 1 study), probiotic yoghurt (n = 1 study), psyllium husk (n = 1 study), prickly pear and olive leaf extract supplement (n = 1 study), and melatonin, amino acid and b-group vitamin supplement (n = 1 study) according to qualitative synthesis. Ginger-containing supplements could be meta-analyzed, and improved incidence of GERD symptom alleviation (n = 2 studies, OR: 7.50 [95%CI: 3.62-15.54], GRADE: high). No clinically and/or statistically significant effects were found for the remaining n = 16 highly heterogenous interventions. CONCLUSION: Evidence to guide the dietary management of GERD symptoms is limited in scope, quality, and feasibility. Based on the limited evidence available, dietary

BACKGROUND: Hypertension is a key modifiable driver of cardiovascular risk and often clusters with dyslipidemia and insulin resistance within the metabolic syndrome. Olive leaf extract (OLE) and potassium have traditionally been used to support blood pressure (BP) management and cardiometabolic health. PURPOSE: To investigate the effect of this OLE - potassium combination on BP and key cardiometabolic markers. STUDY DESIGN: In this randomized, double-blind, placebo-controlled study, 70 adults with untreated mildly to moderately elevated BP received an OLE - potassium supplement (1000 mg OLE, ≥160 mg oleuropein, 300 mg potassium/day) or placebo for 12 weeks. RESULTS: While office BP fell significantly over time in both groups, 7-day home-based BP monitoring showed a significant greater response, with morning systolic BP decreasing by 5.4 mmHg, in the verum group. Supplementation also reduced total cholesterol by 11.1 mg/dL, LDL-cholesterol by 6.9 mg/dL, and triglycerides by approximately 22 mg/dL at Week 6, while HDL-cholesterol remained stable. Fasting glucose and HbA1c were unchanged, but fasting insulin and HOMA-Index declined in the verum group, indicating a modest improvement in insulin sensitivity. Additionally, oxidized LDL decreased by ∼23 %, without changes in hs-CRP. Quality-of-life scores remained stable, although global self-ratings favoured the combination. The intervention was well tolerated, with no product-related serious adverse events. CONCLUSION: The combination of OLE and potassium is a safe adjunctive strategy for individuals with mildly to moderately elevated BP, with favourable effects on lipid profile, oxidative status, and insulin sensitivity that may help reduce cardiometabolic risk in the context of metabolic syndrome.

OBJECTIVES: The aim of this trial was to assess the effects of olive leaf extract (OLE) on blood pressure (BP) control in patients treated for hypertension. METHODS: This is multicenter randomized, double-blind, placebo-controlled trial including 621 participants who were randomly assigned to receive either oral OLE ( n = 307) or placebo ( n = 314). The primary outcome was the change in 24-h SBP and DBP from baseline to week-12. Secondary outcomes included the change in BP load (BPL), BP variability (BPV), metabolic parameters, C-reactive protein (CRP), and body weight. RESULTS: OLE significantly reduced 24-h SBP compared to baseline and placebo group [respectively -6.4 mmHg (95% confidence interval, 95% CI -10 to -2.1) and -1.5 mmHg (95% CI -3.9 to 0.51); P < 0.01]. In OLE group, systolic BPL decreased from 53.9% at baseline to 42.2% at 12-week ( P = 0.03); in placebo group, it did not change significantly ( P = 0.55). Diastolic BPL decreased from 30.7 to 21.2% ( P = 0.03) in OLE group and did not change significantly in placebo group ( P = 0.12). In OLE group, systolic BPV did not change significantly between baseline and week-12 [+2%; P = 0.23] while diastolic BPV significantly decreased [-13.3%; P = 0.04]. In placebo group, BPV did not change significantly at week-12 compared to baseline. OLE was associated with improvement in lipid profile and a significant reduction in blood glucose, triglycerides, CRP, and body weight. No significant adverse events were reported. CONCLUSION: OLE can decrease 24-h BP, BPL, and diastolic BPV with improvement of lipid profile, systemic inflammation, and body weight in hypertensive patients.

The aim of this study was to evaluate whether combined administration of olive leaf extract (OLE) with standard antifungal therapy-nystatin (NYS) or miconazole (MIC) could be a more efficient alternative in reducing the number of Candida colonies, the presence of oral signs and symptoms and changes in salivary IL-17A level compared to standard therapy alone. The study included 59 subjects with a positive microbiological Candida colony number greater than 600 CFU/mL and at least one oral sign or symptom present. Subjects were randomly divided into four groups depending on applied therapy: OLE + NYS group (n = 15), OLE + MIC group (n = 15), NYS group (n = 14), MIC group (n = 15). Therapy duration and clinical monitoring were standardized across all groups. There was no significant difference between the tested groups in Candida spp. colony number or salivary IL-17A levels. In the OLE + NYS group, a significant increase in salivation rate was observed, while a significant decrease in tongue burning was reported in the OLE + MIC group. A significant reduction in burning of the oral mucosa and tongue was observed in the MIC group. No significant differences were found in other clinical signs or symptoms among treatment groups. OLE, as an adjunct to standard antifungal therapy, did not significantly reduce Candida spp. colony number or salivary IL-17A levels. However, in combination with NYS it increased salivation rate, while in combination with miconazole, it significantly decreased tongue burning. Both symptoms are common clinical findings in oral Candida-related disease and suggest that OLE may have supportive potential in the clinical management of these conditions. Further research is needed to explore its potential therapeutic benefits on oral health.

BACKGROUND AND AIM: This trial aimed to investigate the effect of the addition of olive leaf extract (OLE) to a standard calorie-restricted diet on serum oxidative stress markers and liver enzymes. METHODS AND RESULTS: This single-center double-blind, parallel-group, randomized controlled trial was conducted for 8 weeks. Seventy women with obesity (BMI> 30, <40 kg/m2) aged 18 and 50 years were equally assigned to each trial group by randomization. The intervention group received OLE capsules (250 mg olive leaf extract/day), and the placebo group received placebo capsules (250 mg placebo/day) both of them received a calorie-restricted diet. Serum concentration of oxidative stress biomarkers and liver enzymes were assessed at baseline and study endpoint. No significant difference was shown in baseline participant characteristics among the OLE and placebo groups (p > 0.05). At the end of the trial, the OLE group showed a lower concentration of serum malondialdehyde compared to the placebo group (-0.61 ± 0.23 vs -0.48 ± 0.21, p = 0.02), result was also significant after adjustment for confounding factors (p = 0.00). There was, however, no significant difference in serum total antioxidant capacity, Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, and Lactate Dehydrogenase (p > 0.05). CONCLUSIONS: Adding OLE to a hypocaloric diet improves oxidative stress more effectively compared with a hypocaloric diet alone in obese women. TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials (IRCT registration number: IRCT20190129042552N2).

BACKGROUND: The polyphenol oleuropein activates mitochondrial calcium import, which increases pyruvate dehydrogenase (PDH) activity. Preclinically, this increase in PDH activity following oleuropein supplementation resulted in improved mitochondrial bioenergetics and fatigue resistance. OBJECTIVES: This study aimed to examine the effects of acute and chronic oleuropein supplementation on muscle energy metabolism, whole-body substrate metabolism, strength, and fatigue resistance in older males. METHODS: In a randomized, double-blind, placebo-controlled trial, 40 healthy older males (60 ± 5y) received either placebo (PLA) or 100 mg oleuropein from 250 mg olive leaf extract (OLE) supplementation daily for 36 d. On day 1 and day 36, muscle and blood samples were collected, and indirect calorimetry was performed before and ≤120 min following supplement intake. Leg strength and fatigue were measured before and after 29 d of supplementation. Results were analyzed using analysis of covariance or robust analysis of covariance. RESULTS: OLE ingestion on day 1 and day 36 increased plasma oleuropein metabolites (P < 0.001). On day 1, no differences were observed in muscle PDH activity, mitochondrial respiration, or whole-body substrate metabolism 120 min after acute OLE ingestion. Ribonucleic acid sequencing revealed upregulation of oxidative phosphorylation gene pathways (false discovery rate < 0.05), whereas PDH-Serine293-phosphorylation was higher after acute OLE compared with PLA ingestion (P = 0.015). Following chronic supplementation, fractional PDH activity was ∼25% greater in OLE compared with PLA (49 ± 14 compared with 38 ± 10%; P = 0.016) with no differences in absolute PDH activity and PDH-Serine293-phosphorylation between groups. Mitochondrial respiration and protein content, whole-body substrate metabolism, leg strength, and fatigue resistance were not different between OLE and PLA. Plasma low-density lipoprotein cholesterol was lower after chronic OLE compared with PLA (P = 0.043), with no differences in other blood metabolic markers. CONCLUSIONS: Chronic OLE supplementation resulted in higher skeletal muscle fractional PDH activity in healthy, older males, wh

INTRODUCTION: Osteoarthritis is a progressive joint disease that affects one or more joints, leading to restricted movement, pain, and eventual disability. Despite the availability of various treatments and supportive care, managing osteoarthritis symptoms remains challenging. This study aimed to evaluate the effect of Hydroalcoholic olive leaf extract on pain reduction and daily functioning in elderly patients with knee osteoarthritis. METHOD: A randomized, controlled, factorial clinical trial was conducted in 2022-2023 with 100 elderly participants suffering from knee osteoarthritis. Participants were selected through consecutive sampling and randomly assigned to four groups using block-stratified randomization. In addition to routine treatment, participants in group I received topical olive leaf extract ointment, Group II received oral olive leaf extract capsules, and Group III received a combination of both treatments. The intervention was administered three times daily for eight weeks. The control group did not receive any olive leaf extract-based interventions. Pain intensity was assessed using a visual analog scale, and daily functioning and joint stiffness were measured using the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire. Data were analyzed using SPSS software. RESULTS: The intervention groups showed significantly more significant reductions in mean pain scores than the control group (p < 0.05). The combination of oral capsules and topical ointment among the intervention groups demonstrated the most pronounced pain reduction. The mean score for daily functioning improved significantly over time in all groups (p = 0.007). A decrease of 1.19 units per time increment was observed in the group using the ointment, while the oral capsule group showed a decrease of 0.89 units, both statistically significant (p = 0.006). CONCLUSION: Hydroalcoholic olive leaf extract effectively reduces pain and improves physical functioning in elderly patients with knee osteoarthritis, offering a promising complementary treatment option for managing osteoarthritis symptoms.

BACKGROUND: Maintaining optimum glycaemic control is essential to reducing comorbidity and mortality in diabetes. However, research indicates that <50 % of patients achieve their target HbA1c ranges. Laboratory studies suggest that olive leaf extract (OLE) may improve glycaemic control, however clinical studies in persons with diabetes are lacking. METHODS: ESOLED is a pilot, randomised, placebo-controlled trial. Adults with a diagnosis of type 2 diabetes of ≥12 months duration, and not receiving insulin therapy, were eligible to participate. Participants were randomised to receive OLE or placebo capsules for 24 weeks. The primary outcome was change in HbA1c. Secondary outcomes included changes in the homeostasis model assessment of insulin resistance, diabetes-related stress, health-related quality of life, and safety. RESULTS: Thirty-one participants were randomly assigned to the OLE (n = 16) and placebo (n = 15) groups. Analyses found no statistically significant time-group interactions for HbA1c, diabetes-related distress or health-related quality of life. Although participants receiving OLE demonstrated greater improvements in insulin sensitivity than those on placebo, there was no significant difference between groups over time. OLE and placebo were found to be well-tolerated, with no severe or serious adverse events reported in either group. CONCLUSION: The ESOLED trial has provided preliminary evidence on the tolerability of OLE in adults with type 2 diabetes, but was inconclusive in determining whether OLE is effective at improving glycaemic control, insulin sensitivity, diabetes-related distress and quality of life. Larger trials and further exploration of the bioavailability of OLE are needed to fully assess the therapeutic potential of OLE in diabetes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12622000616774).

Recurrent herpes labialis (RHL) is a lifelong oral health issue that affects about one-third of the world's population, causing frequent, painful, and discomfort lesions. This randomized, triple-blinded study aimed to evaluate the effectiveness of olive leaf extract (OLE) compared to acyclovir cream (Veramid 5%) in managing vesicular stage of RHL lesions. Forty patients were randomly divided into two equal groups and were instructed to apply the prescribed medication five times a day for five consecutive days. The evaluation was carried out by measuring the pain intensity on the first day before the treatment was applied (T0), 48 h (T1), and 7 days later (T2). Additionally, the day when the pain completely healed and the day when the lesion's crust fell off spontaneously were recorded. Statistical analysis was conducted using the Mann-Whitney test at a significance level of α = 0.05. The study results indicated that there were no significant differences in pain intensity between the two groups during the three evaluation times: T0 (P = 920), T1 (P = 0.596), and T2 (P = 1.00). Furthermore, there was no significant difference in the day when the pain was completely healed (P = 0.697). However, the OLE showed a statistically significant advantage regarding the day the lesions' crust fell off (P = 0.040). In conclusion, OLE may be a potential alternative treatment for RHL.Trial registration: isrctn.com ID: ISRCTN87606522, 04/09/2023. © 2024. The Author(s).

Menopause negatively impacts women's health. Objectives: The aim of this study was to investigate whether an olive leaf extract (OLE) improves postmenopausal symptoms, body composition, handgrip strength and blood lipid profile in postmenopausal women. In a randomized, double-blinded parallel study design, 60 healthy postmenopausal women aged 47-70 years received either OLE (250 mg/day) or placebo supplementation for 12 weeks. Postmenopausal symptoms were assessed with the Menopause-Specific Quality of Life Questionnaire (MENQoL), the Hot Flash Interference scale (HFI), and body composition and bone mineral density (BMD) with a DXA scan; the lipid profile was measured in the blood serum. After six and twelve weeks of OLE supplementation, the overall MENQoL score significantly improved (estimated mean difference [95% CI]: -0.2 [-0.4-0.2], p = 0.027) compared to the placebo. A significant improvement (+0.017 [0.003, 0.030], p = 0.019) was recorded in the BMD in the right arm in the OLE group compared to the placebo. The intervention did not affect other body composition outcomes. TG concentrations and the TG/HDL-C ratio were significantly decreased (-0.1 [-0.2, 0.0], p = 0.010; -0.1 [-0.2, -0.0], p = 0.029, respectively) in the OLE group compared to the placebo. Twelve weeks of daily OLE supplementation improved postmenopausal symptoms. Further studies are needed to elucidate the mechanisms underlying the observed effects.

Certain nutraceuticals, mainly containing red yeast rice, might be considered as an alternative therapy to statins in patients with dyslipidemia, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing a low dose of monacolin K combined with coenzyme Q10, grape seed and olive tree leaf extracts in patients with mild hypercholesterolemia. In total, 105 subjects with mild hypercholesterolemia (low-density lipoprotein cholesterol LDL-C levels 140-180 mg/dL) and low CV risk were randomly assigned into three treatment groups: lifestyle modification (LM), LM plus a low dosage of monacolin K (3 mg), and LM plus a high dosage of monacolin K (10 mg) and treated for 8 weeks. The primary endpoint was the reduction of LDL-C and total cholesterol (TC). LDL-C decreased by 26.46% on average (p < 0.001) during treatment with 10 mg of monacolin and by 16.77% on average during treatment with 3 mg of monacolin (p < 0.001). We observed a slight but significant reduction of the triglyceride levels only in the high-dose-treated group (mean -4.25%; 95% CI of mean -11.11 to 2.61). No severe adverse events occurred during the study. Our results confirm the LDL-C-lowering properties of monacolin are clinically meaningful even in lower doses of 3 mg/day.

Despite recent medical progress, cervical cancer remains a major global health concern for women. Current standard treatments have limitations such as non-specific toxicity that necessitate development of safer and more effective therapeutic strategies. This research evaluated the combinatorial effects of olive leaf extract (OLE), rich in anti-cancer polyphenols, and the oncolytic Newcastle disease virus (NDV) against human cervical cancer cells. OLE was efficiently encapsulated (>94% loading) within MF59 lipid nanoparticles and nanostructured lipid carriers (NLCs; contains Precirol as NLC-P, contains Lecithin as NLC-L) to enhance stability, bioavailability, and targeted delivery. Physicochemical analysis confirmed successful encapsulation of OLE within nanoparticles smaller than 150 nm. In vitro cytotoxicity assays demonstrated significantly higher toxicity of the OLE-loaded nanoparticle formulations on HeLa cancer cells versus HDF normal cells (P<0.05). MF59 achieved the highest encapsulation efficiency, while NLC-P had the best drug release profile. NDV selectively infected and killed HeLa cells versus HDF cells. Notably, combining NDV with OLE-loaded nanoparticles led to significantly enhanced synergistic cytotoxicity against cancer cells (P<0.05), with NLC-P (OLE) and NDV producing the strongest effects. Apoptosis and cell cycle analyses confirmed the increased anti-cancer activity of the combinatorial treatment, which induced cell cycle arrest. This study provides evidence that co-delivery of OLE-loaded lipid nanoparticles and NDV potentiates anti-cancer activity against cervical cancer cells in vitro through a synergistic mechanism, warranting further development as a promising alternative cervical cancer therapy. Copyright: © 2024 Golalipour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

The African wild olive (Olea europaea subsp. africana) is traditionally used as a hypotensive agent. Herb-drug interactions may result from the concurrent use of herbal medicines and conventional prescription drugs. This aspect was investigated by determining the effect of the extract on the in vitro intestinal epithelial permeation of selected hypotensive drugs using the Caco-2 cell culture model. The phytochemical profiles of leaf extracts of African wild olive from different localities in South Africa were compared, since efficacy is determined by the chemical composition. Extracts were analysed using ultra-performance liquid chromatography. The oleuropein concentration varied considerably from below the detection limit (4.94 µg/mL) to 59.4 mg/g dry weight. Chemometric models constructed from the aligned chromatographic data indicated only quantitative differences between the profiles. The leaf extract was found to increase the permeability of propranolol in the absorptive direction (Papp = 8.93 × 10-6 cm/s) across Caco-2 cell monolayers, but considerably decreased transport in the secretory direction (Papp = 3.68 × 10-6 cm/s). The permeation of diltiazem was enhanced by the extract in both the absorptive (Papp = 7.33 × 10-6 cm/s) as well as in the secretory direction (Papp = 7.16 × 10-6 cm/s), but a decrease in the efflux ratio was observed. The extract therefore caused a net increase in the transport of both drugs in the absorptive direction due to an inhibition effect on their efflux. This suggests a potential increase in the blood levels of these drugs when taken simultaneously with African wild olive leaf extract, indicating potential adverse effects that must be verified in vivo. Georg Thieme Verlag KG Stuttgart · New York.

Patients with glioblastoma multiforme (GBM) that are cancer stem-cell-positive (GSC [+]) essentially cannot benefit from anti-angiogenic or anti-invasive therapy. In the present study, the potential anti-angiogenic and anti-invasive effects of Olea europaea (olive) leaf extract (OLE) were tested using GSC (+) tumours. OLE (2mg/mL) caused a significant reduction in tumour weight, vascularisation, invasiveness and migration (p=0.0001, p<0.001, p=0.004; respectively) that was associated with reducing the expression of VEGFA, MMP-2 and MMP-9. This effect was synergistically increased in combination with bevacizumab. Therefore, our current findings may contribute to research on drugs that inhibit the invasiveness of GBM.

The antimicrobial properties of olive leaf extract (OLE) have been well recognized in the Mediterranean traditional medicine. Few studies have investigated the antimicrobial properties of OLE. In this preliminary study, commercial OLE and its major phenolic secondary metabolites were evaluated in vitro for their antimicrobial activities against Escherichia coli and Staphylococcus aureus, both individually and in combination with ampicillin. Besides luteolin 7-O-glucoside, OLE and its major phenolic secondary metabolites were effective against both bacteria, with more activity on S. aureus. In combination with ampicillin, OLE, caffeic acid, verbascoside and oleuropein showed additive effects. Synergistic interaction was observed between ampicillin and hydroxytyrosol. The phenolic composition of OLE and the stability of olive phenols in assay medium were also investigated. While OLE and its phenolic secondary metabolites may not be potent enough as stand-alone antimicrobials, their abilities to boost the activity of co-administered antibiotics constitute an imperative future research area.

Introduction: Herpes labialis, commonly caused by herpes simplex virus type 1, affects millions globally and is traditionally managed with nucleoside antiviral drugs. However, increasing interest in complementary and integrative therapies has led to the exploration of topical herbal treatments as potential alternatives or adjuncts in managing this condition. Methods: A systematic review was conducted in accordance with Cochrane guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations, with prior registration. A comprehensive search of Medline/PubMed, Scopus, and the Cochrane Central Register of Controlled Trials was performed from inception to June 17, 2024. After screening 7,386 nonduplicate records and assessing 346 full-text articles, 7 randomized controlled trials (RCTs) encompassing 1,250 patients were included. Data were extracted regarding intervention types, outcomes, and adverse events, and the risk of bias was evaluated using the Cochrane Risk of Bias Tool. Results: The included studies evaluated topical formulations of lemon balm (Melissa officinalis L.), olive leaf extract (Olea europaea L.), propolis, and a combined sage-rhubarb cream (Salvia officinalis L., Rheum palmatum L., and Rheum officinale Baill.). Lemon balm preparations consistently reduced pain intensity and swelling, with some studies also reporting a significant decrease in lesion size compared with placebo or acyclovir. Olive leaf extract demonstrated a statistically significant faster improvement in symptoms and a shorter healing time compared with acyclovir. Compared with acyclovir, propolis formulations significantly shortened the median time to lesion encrustation and complete healing compared with acyclovir, and the combined sage-rhubarb cream showed a comparable efficacy to acyclovir in mean healing time. Overall, the risk of bias was judged to be low in two trials, while five trials raised some concerns. The total sample size across studies was small, potentially limiting the generalizability of the results. Across all studies, adverse events were minimal or absent. Discussion: The findings indicate that topical herbal therapies may provi

CONTEXT: Olive leaf extract (OLE) is rich in phenolic compounds, which are known for their health benefits. Cardiovascular diseases, primarily coronary heart disease and stroke, are leading causes of mortality globally. OBJECTIVE: This systematic review aimed to assess the impact of OLE on cardiometabolic risk factors in adults. The selection of studies was based on intervention and outcomes, using relevant search descriptors. DATA SOURCES: The databases PubMed, EMBASE, and Web of Science were systematically searched for pertinent studies published up to August 2021. DATA EXTRACTION: Only randomized clinical trials, either cross-over or parallel, involving adult individuals aged ≥18 years, were considered. Additionally, trials that had a comparative or placebo group and used pure OLEs for oral treatment were included. DATA ANALYSIS: Twelve randomized clinical trials (RCTs) met the inclusion criteria. These trials had follow-up periods ranging from 2 days to 12 weeks and involved 703 patients aged 18 years-79 years. The outcomes demonstrated a positive correlation between the intervention group and glucose metabolism (4 RCTs), blood pressure (2 RCTs), lipid profile (2 RCTs), and inflammatory markers (2 RCTs). The RoB2 tool and the GRADE system were used to evaluate the risk of bias and the quality of evidence in the studies. CONCLUSIONS: In the meta-analysis, fasting glycemia, as evaluated in studies using a low dose of OLE, showed a significant result favoring the control group. To obtain more consistent results, further clinical studies in humans, using similar methodologies, are required. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020200877. © The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: [email protected].