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Olive Leaf

Scientific Name(s): Olea europaea L.
Common Name(s): OLE, Olive leaf, Olive leaf extract

Medically reviewed by Drugs.com. Last updated on Oct 1, 2022.

Clinical Overview

Use

Clinical trials have been conducted to evaluate the anti-infective/antiviral, anti-inflammatory, antioxidant, and hematologic activities of olive leaf, as well as its possible roles in diabetes and cardiovascular conditions. However, clinical trial data are lacking to recommend use for any indication.

Dosing

Many commercial olive leaf and olive leaf extract preparations of varying strengths are available.

One clinical trial in patients with stage 1 hypertension used an olive leaf extract dosage of 500 mg twice daily for 8 weeks. Supplementation with olive leaf extract (equating to a daily dose of oleuropein 51.1 mg and hydroxytyrosol 9.7 mg) for 12 weeks was examined in a crossover study evaluating effects on insulin action and cardiovascular risk factors in men with a BMI of 28 (±2) kg/m2.

Contraindications

Contraindications have not been identified. Caution may be warranted in hepatic disease.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy during pregnancy and lactation is lacking.

Interactions

Olive leaf may enhance the hypotensive effect of blood pressure–lowering agents or other herbal products with blood pressure–lowering effects.

Adverse Reactions

None well documented. Patients with diabetes should be supervised carefully because of potential hypoglycemic effects.

Toxicology

Information is limited. Moodiness and aggressive behavioral changes likely related to olive leaf extract (at a dose of 85 mg/kg) have been reported in an elderly woman.

Scientific Family

Botany

The olive tree (O. europaea) is an evergreen that grows to approximately 10 m in height. Native to Mediterranean regions, olive trees are also cultivated in similar climate zones in the Americas. The small, leathery leaves are gray-green on top, and the undersides contain fine, white, scale-like hairs. The leaves are gathered throughout the year.(Chevallier 1996, USDA 2022, Weiss 1988)

History

The olive tree was cultivated in Crete, where the leaves were used to clean wounds as early as 3500 BC. The leaves were worn by athletes in ancient Olympic Games, and the olive branch has traditionally been a symbol of peace. In the 1800s, olive leaf was used to treat malaria.(Bruneton 1995, Chevallier 1996, Lee-Huang 2003, Weiss 1988)

Chemistry

Olive leaf contains the iridoid oleuropein (up to 240 mg per gram of dry leaves).(de Bock 2013) Other secoiridoids include demethyloleuropein, esters of oleoside, ligustroside, oleuroside, and unconjugated secoiridoid aldehydes. Triterpenes and flavonoids are also present, including luteolin and related glucopyranosides, tyrosol and hydroxytyrosol, apigenin, rutin, and diosmetin. Other compounds found in the leaves are oleasterol, leine, choline, cinconine, olivine, tannin, calcium, phosphorus, carbohydrates, fat, and fiber.(Benavente-Garcia 2000, Briante 2002, Duke 1992, Kontogianni 2012, Meirinhos 2005, Petkov 1972)

Uses and Pharmacology

Antidiarrheal effects

Animal data

A study in mice with castor oil–induced diarrhea suggested that olive leaf extract reduced the number of diarrheal episodes and could affect gastric transit time.(Amabeoku 2010)

Anti-infective effects

Animal and in vitro data

In vitro studies demonstrate activity against a range of human pathogens,(Bisignano 1999, Lee 2010, Markin 2003) as well as against Leishmania species.(Sifaoui 2014) In a systematic review (in vitro and in vivo experiments), olive leaves were noted to be one of 6 plants most effective against Acanthamoeba.(Chegeni 2020) Animal experiments and in vitro studies suggest that olive leaf extracts possess antiviral activity.(Lee-Huang 2003, Micol 2005) In an in vitro experiment, cell-to-cell transmission of HIV was inhibited in a dose-dependent manner, and HIV-1 replication was inhibited.(Lee-Huang 2003) In vitro activity against rotavirus and influenza virus has been demonstrated.(Knipping 2012, Salamanca 2021) A US patent claimed oleuropein had antiviral activity against herpes mononucleosis, hepatitis virus, rotavirus, bovine rhinovirus, canine parvovirus, and feline leukemia virus.(Fredrickson 2000, Omar 2010)

Clinical data

In high school athletes enrolled in a 2-month double-blind, randomized, controlled trial (N=32), olive leaf extract significantly reduced sick days (28% reduction; P=0.02 vs placebo) but demonstrated no significant effect on the average duration or frequency of upper respiratory infections. Subgroup analysis revealed the reduction in sick days was significant in females (P<0.01) while a significant increase was observed in males (P<0.05). In the context of training load, the extract was found to have a possibly harmful effect on soreness and a likely harmful effect on stress. Adverse events reported for olive leaf extract were stomach ache and headaches (n=3) and bad skin/acne (n=1).(Somerville 2019) Topical application of olive leaf extract twice daily for 6 days to the perineal and rectal regions of a 19-year-old female was successful in treating acyclovir-resistant herpes infection. Pain and wounds resolved on day 3, and lesions had completely disappeared on day 6 with no relapse observed 2 weeks after treatment.(Lorzadeh 2020) Comparison of an olive leaf 2% oil cream with acyclovir 5% cream for the treatment of oral herpes simplex in 33 patients showed olive leaf cream to be superior, with faster healing and fewer symptoms of bleeding, itching, and pain.(Toulabi 2022)

Anti-inflammatory effects

Animal and in vitro data

In rat, mice, and rabbit studies, olive leaf extract decreased production of proinflammatory cytokines. Studies have included models of allergic asthma, osteoarthritis, colitis, wound healing, and gout (xanthine oxidase inhibition).(Cvjetićanin 2010, Fakhraei 2014, Flemmig 2011, Gong 2012, Gong 2011, Koca 2011, Rouibah 2022, Sandoval-Ramirez 2021)

In colonic mucosa tissue obtained via biopsies from 14 patients with mild to moderate active ulcerative colitis, olive leaf extract significantly reduced inflammatory damage; decreased infiltration of leukocytes and preservation of mucin secretion and goblet cells were observed.(Larussa 2017) In osteoarthritis mice models, improvements in symptoms were attributed to increases in hyluronan.(Takuma 2018)

Clinical data

A small (N=25) clinical study evaluated the effect of olive leaf extract (equivalent to 10 mg/day of hydroxytyrosol) for 4 weeks versus placebo in osteoarthritis of the knee. Improved scores on pain rating scales were achieved.(Takeda 2013) Efficacy of daily olive leaf extract containing oleuropein 50 mg was tested in a 6-month study of 124 patients with knee osteoarthritis. Despite improvements with the extract, the difference from placebo was not significant for the study population as a whole. However, in subjects with a high level of pain with walking, reductions in pain and symptoms (as measured by the Knee injury Osteoarthritis Outcome Score) were clinically significant.(Horcajada 2022)

A crossover clinical study evaluated olive leaf extract (in the form of a mouth rinse) for efficacy in oral mucositis caused by chemotherapy in 25 patients. At 2 weeks, significantly lower rates and severity of mucositis, as well as downregulation of tumor necrosis factor (TNF) and interleukin (IL)-1 beta, were observed compared with placebo.(Ahmed 2013)

In a study in hypertensive patients (N=60), significant reductions in IL-6 (P=0.038), IL-8 (P=0.043), and TNF-alpha (P=0.015) were observed with a 2-month regimen of olive leaf extract compared with placebo.(Javadi 2019) In another study in which prehypertensive males (N=60)received olive leaf extract (standardized to contain 6.6 to 7.9 oleuropein/mL) 20 mL/day for 16 weeks, only IL-8 was significantly improved while IL-6, IL-10, IL-1beta, and TNF-alpha levels remained similar to controls.(Lockyer 2017)

In a study of 32 patients with rheumatoid arthritis, addition of a dry olive leaf extract to a methotrexate regimen provided increased benefits (eg, greater IL-6 suppression) with short-term treatment (ie, 3 weeks), but no difference was observed with long-term treatment (ie, 6 weeks).(Čabarkapa 2016)

Antioxidant activity

Animal and in vitro data

In vitro studies have demonstrated antioxidant activity of olive leaf extracts, including a reduction in cyclooxygenase-2 levels.(Benavente-Garcia 2000, Briante 2002, Caturla 2005, De Marino 2014, Koca 2011, Larussa 2017, Lee 2010, Türkez 2011, Visioli 2002)

Studies in rodents have shown antioxidant activity in allergic asthma, brain tissue injury, gentamicin-induced nephrotoxicity, fluoxetine-induced liver injury, reperfusion injury, major organ injury, induced gastric ulceration, and lead toxicity, as well as in other conditions.(Al-Attar 2013, Al-Azzawie 2006, Alirezaei 2012, Çoban 2014, Dekanski 2011, Elgebaly 2018, Rouibah 2022, Seddik 2011, Tavafi 2012, Turkez 2012, Wang 2013, Zaslaver 2005)

Clinical data

The oral bioavailability of olive leaf extract and associated antioxidant biomarkers was evaluated in a study in pre- and postmenopausal women (N=16). The findings suggest that postmenopausal status increases the production of olive leaf extract metabolites. Findings suggest olive phenolic intake could be beneficial in postmenopausal women to prevent age-related and oxidative stress–related processes.(García-Villalba 2014) In young, healthy volunteers (N=45), supplementation with olive leaf extract did not alter oxidative status, and wide interperson variability was observed.(Kendall 2009)

Cancer

Animal and in vitro data

In vitro studies using olive leaf extract have demonstrated growth inhibition against human cancer cell lines, as well as cell cycle suppression, cell membrane disruption, increased ROS production, and apoptosis. Activity has been demonstrated in breast, colon, prostate, neuroblastoma cells, and others.(Albogami 2021, Anter 2011, Belščak-Cvitanović 2014, Benot-Dominguez 2021, Cabarkapa 2014, Elamin 2013, Morandi 2021, Samet 2014, Tezcan 2014, Tunca 2012) In one study in mice, activity against melanoma was demonstrated. When olive leaf extract was combined with different chemotherapeutics, antagonism and synergy were observed.(Mijatovic 2011)) Similarly, olive leaf extract demonstrated pro-apoptotic activity in a mouse mammary model in which tumor volume was significantly reduced and apoptosis increased in a dose-dependent manner.(Milanizadeh 2019)

Cardiovascular risk factors

Animal and in vitro data

In experiments in rabbit and rat tissue preparations, oleuropein had a hypotensive effect, possibly via direct action on smooth muscle. Oleuropein also may exert vasodilator activity. In another study in rats with metabolic syndrome, olive leaf extract had no effect on blood pressure, despite improving lipid profile and glucose tolerance.(Poudyal 2010) Olive leaf extracts may also possess antispasmodic, vasodilator, and antiarrhythmic properties.(Khayyal 2002, Zarzuelo 1991) In a rat model of stroke, pretreatment with olive leaf for 30 days attenuated the biochemical effects induced by brain ischemia.(Rabiei 2012) In rabbits pretreated with olive leaf extract for 8 weeks, prothrombin time was prolonged and the morphology of induced thrombi differed from that of untreated animals. Activated partial prothrombin time was unaffected.(Dub 2013)

Clinical data

A randomized clinical trial in patients with stage 1 hypertension compared the effectiveness of olive leaf extract with that of captopril in reducing systolic blood pressure (SBP). Olive leaf extract 500 mg twice daily over 8 weeks resulted in a mean SBP reduction of 11.5±8.5 mm Hg, compared with a reduction of 13.7±7.6 mm Hg with captopril (P=0.098). Triglycerides were also reduced, but no other biochemical indices were altered.(Susalit 2011)

Results regarding effects of olive leaf extract on metabolic and lipid parameters in patients who were prehypertensive, hypertensive, and/or overweight and obese have been inconsistent.(Javadi 2019, Lockyer 2017, Stevens 2021) A 12-week double-blind, randomized, placebo-controlled study in 60 hypertensive patients demonstrated no significant effects for olive leaf extract on metabolic (ie, fasting blood glucose, insulin, homeostatic model assessment of insulin resistance [HOMA-IR]) or liver and kidney function compared with controls. In contrast, biomarkers of inflammation (ie, IL-6, IL-8, TNF-alpha) were significantly reduced with the extract (P<0.05 vs placebo for each). No adverse events were reported.(Javadi 2019) In prehypertensive males enrolled in a double-blind, randomized, placebo-controlled crossover study (N=60), 10 mL of concentrated olive leaf extract liquid twice daily for 16 weeks significantly reduced several blood pressure measures compared with controls (P<0.05) by a mean of approximately 3 mm Hg. Arterial stiffness remained similar between groups. Biochemical analysis revealed reductions in IL-8 (P<0.05), total cholesterol (−32 mmol/L; P=0.002), LDL (−0.19 mmol/L, P=0.017), and triglycerides (−0.18 mmol/L, P=0.008) with the extract compared with controls and no significant differences in other inflammatory cytokines (ie, IL-6, IL-10, IL-1beta, TNF-alpha), metabolic parameters (ie, fasting glucose, insulin, fructosamine, HOMA-IR), or lipids (ie, HDL, LDL:HDL ratio, total:HDL ratio).(Lockyer 2017) However, in another double-blind, randomized, placebo-controlled study that enrolled 77 patients with a body mass index of 25 to 35 kg/m2 and elevated cholesterol (5 to 8 mmol/L), 500 mg/day of an aqueous olive leaf extract for 8 weeks did not significantly affect lipid, hemodynamic (SBP, mean arterial pressure, pulse pressure, heart rate), or metabolic (glucose, insulin) parameters.(Stevens 2021)

A systematic review of 5 trials investigating the effect of olive leaf extract on prehypertensive and hypertensive adults (N=325) determined that data were insufficient to perform a meta-analysis. Based on low-quality evidence, olive leaf extract does not appear to significantly affect blood pressure and demonstrated no significant effects on lipid or glucose parameters. Biomarkers of inflammation (ie, Il-6, IL-8, TNF-alpha) were more often reduced with the extract than with placebo. The extract seemed to be safe, with similar effects on kidney and liver function as placebo.(Ismail 2021)

CNS effects

Animal and in vitro data

One study evaluating olive leaf extract showed a dose-dependent analgesic effect in rats,(Esmaeili-Mahani 2010) and a study by the same group of researchers showed olive leaf extract also prevented morphine tolerance in rats.(Zare 2012) Another study in rats demonstrated decreased neuropathic pain.(Kaeidi 2011) In an in vitro model of Parkinson disease, olive leaf extract inhibited adrenal pheochromocytoma cell damage via antioxidant and antiapoptotic activity.(Pasban-Aliabadi 2013) Olive leaf administered as both an extract and as tea attenuated the clinical course and reduced mortality in a rat model of autoimmune encephalomyelitis. Effects were the result of antioxidant and immunomodulatory activity that improved myelin integrity.(Giacometti 2020) In a mouse model of Alzheimer disease, an oleuropein-rich extract of olive leaf given orally reduced the production and increased the clearance of amyloid-beta proteins and also reduced inflammation via inhibition of the nuclear factor kappa B pathway.(Abdallah 2022) Neuroprotective effects were also observed for both amyloid-beta and tau proteins via the insulin-like signaling pathway in a Caenorhabditis elegans model.(Romero-Márquez 2022) Inhibition of oxidative stress resulted in neuroprotection of cognitive activity in an induced diabetes rat model.(Asghari 2022)

Diabetes

Animal data

Studies in rodents consistently report decreased blood glucose levels.(Kontogianni 2013, Park 2013, Poudyal 2010) In addition, reduced triglycerides and cholesterol have been observed.(El-Amin 2013, Liu 2014) In rats fed a high-fat diet, olive leaf extract positively modulated adipogenesis and thermogenesis.(Shen 2014) Suggested mechanisms include potentiation of glucose-induced insulin release and increased peripheral uptake of glucose.(Al-Azzawie 2006, Cumaoğlu 2011, Gonzalez 1992)

Clinical data

In patients with type 2 diabetes (N=79), 500 mg of olive leaf extract daily significantly decreased hemoglobin A1c and fasting plasma insulin levels versus placebo; however, it had no effect on postprandial plasma insulin.(Wainstein 2012) A 12-week crossover study conducted in men with a BMI of 28 (±2) kg/m2 (N=46) showed a 15% increase (P=0.024) in insulin sensitivity with olive leaf extract (equating to a daily dose of oleuropein 51.1 mg and hydroxytyrosol 9.7 mg) versus placebo. In addition, increased pancreatic beta-cell responsiveness was observed. No effect on lipid profile, blood pressure, body composition, or liver function was reported.(de Bock 2013) Another study suggests acute hypoglycemic benefits with olive leaf extract in individuals with prediabetes and with less healthy metabolic profiles.(Lim 2021)

Hematological effects

Clinical data

In a randomized controlled trial (N=32), women with borderline to mildly elevated LDL cholesterol who consumed olive leaf tea for 12 weeks had significant increases in red blood cells, hemoglobin, and hematocrit (P<0.05 unpaired t-test) compared with women who consumed green tea.(Ferdousi 2019)

Hypopigmentation

In vitro data

Observed olive leaf activity may indicate a potential role in the treatment of hypopigmentation disorders. An in vitro study of a dry powder olive leaf extract demonstrated increased extracellular melanin and melanocyte dendricity.(Goenka 2021)

Liver disease

Animal data

Olive leaf powder was protective against development of nonalcoholic fatty liver in rats fed a high-fat and high-cholesterol diet.(Omagari 2021)

Obesity

Animal data

In a modern obesity mouse model characterized by high caloric intake and physical inactivity, olive leaf extract prevented significant body weight gain and increased lipolysis. Additionally, some of the cognitive decline and depressive behavior observed in the untreated obese/inactive model were mitigated with the extract.(Mikami 2021)

Performance

Clinical data

Results reported in the abstract of a conference presentation noted a non-significant decrease in the performance of 15 active young adults aged 18 to 35 years during the olive leaf extract phase compared to the control phase in a randomized crossover trial.(Somerville 2021) In another small crossover study (N=9) conducted in young, healthy male athletes, olive leaf extract enriched with oleuropein upregulated tryptophan (the precursor to serotonin) and increased circulating acylcarnitines in both serum and urine, which has been shown previously to positively affect endurance and sensation of effort. Overall, 29 different metabolites were identified during the extract phase compared to the placebo phase.(Lemonakis 2022)

Thyroid activity

Animal data

An aqueous extract of olive leaf administered to rats for 14 days increased triiodothyronine levels and reduced circulating thyroid-stimulating hormone levels, possibly via a feedback mechanism.(Al-Qarawi 2002) A systematic review identified 4 animal studies and no human studies that confirmed a thyroid-stimulating effect of olive leaf extract in euthyroid animal models, as well as thyroid protective effects in animals under heat-stress or with chemically induced hypothyroid.(Pang 2021)

Dosing

Many commercial olive leaf and olive leaf extract preparations of varying strengths are available. Based on studies with healthy volunteers, olive leaf extracts appear to be more bioavailable in liquid than in capsule or tablet form, with wide individual variation.(de Bock 2013)

One clinical trial in patients with stage 1 hypertension used an olive leaf extract dosage of 500 mg twice daily for 8 weeks.(Susalit 2011) Supplementation with olive leaf extract (equating to a daily dose of oleuropein 51.1 mg and hydroxytyrosol 9.7 mg) for 12 weeks was examined in a crossover study evaluating effects on insulin action and cardiovascular risk factors in men with a BMI of 28 (±2) kg/m2.(de Bock 2013)

Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy during pregnancy and lactation is lacking.

Interactions

A study in mice showed both antagonism and synergy with olive leaf extract applied in combination with various chemotherapeutics; use caution with concomitant chemotherapy.(Mijatovic 2011)

An in vitro study suggests that blood levels of diltiazem and propranolol may increase when taken with olive leaf.(Mmopele 2018)

Blood pressure–lowering agents: Herbal products with blood pressure–lowering effects may enhance the hypotensive effect of blood pressure–lowering agents. Monitor therapy.(Askarpour 2019, Ismail 2021, Lan 2015, Najafpour Boushehri 2020, Zhang 2020)

Herbal products with blood pressure–lowering effects: Herbal products with blood pressure–lowering effects may enhance the hypotensive effect of other herbal products with blood pressure–lowering effects. Monitor therapy.(Askarpour 2019, Ismail 2021, Lan 2015, Najafpour Boushehri 2020, Zhang 2020)

Adverse Reactions

None well documented. Individuals with diabetes should be supervised carefully because of potential hypoglycemic effects with olive leaf extract use. Hepatotoxicity has been demonstrated in 1 animal study (see Toxicology).(Arantes-Rodrigues 2011) In a study in rabbits, pretreatment with an ethanolic olive leaf extract increased prothrombin times.(Dub 2013)

Toxicology

The potential toxicity of olive leaf is not well documented. In mice fed 0.5% to 0.75% olive leaf extract ad libitum for 14 weeks, increased liver enzymes, hyperplasmia of the bile ducts, cholestasis, and hepatic fibrosis and necrosis were observed.(Arantes-Rodrigues 2011)

Oleuropein at dosages up to 1 g/kg of body weight was not lethal in albino mice.(Petkov 1972) At 1 mg/mL, an extract of olive leaf was not toxic to human cells.(Lee-Huang 2003) Olive leaf extract has an estimated oral median lethal dose of more than 3,000 mg/kg in mice.(Arantes-Rodrigues 2011, Duke 2002) However, a case of a 67-year-old female experiencing unusual moodiness and aggressive behavior after taking olive leaf extract (5.5 g dry olive leaf per day) for hay fever suggests that an olive leaf extract dose of 85 mg/kg body weight is toxic. The authors hypothesized that hydroxytyrosol, a constituent of olive leaf extract that is structurally similar to dopamine, could have caused changes in synaptosomal dopamine levels.(Shaw 2016)

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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