Olive Leaf

Metadata

Approved Indications

Commission E (Germany)

• No Commission E monograph exists for Olea europaea leaf
• The Commission E era (1978-1994) did not evaluate olive leaf for hypertension

ESCOP Monograph

• No ESCOP monograph for olive leaf at time of research [NEEDS-RESEARCH]

EMA/HMPC

• Traditional use monograph on Olea europaea L., folium
• Registered indication: Traditional herbal medicinal product used to promote renal elimination of water, in mild cases of water retention, after serious conditions have been excluded by a physician
• NOT registered for hypertension — the HMPC monograph does not include blood pressure reduction as an approved indication
• Assessment report acknowledges the long-standing traditional use of olive leaf in Mediterranean countries
• Restricted to adults

Agreement/Disagreement Between Bodies

• Significant gap between clinical evidence (Susalit trial showing non-inferiority to captopril) and regulatory recognition (only traditional use for water retention)
• No European regulatory body has formally approved olive leaf for hypertension
• This is partly because the evidence base, while promising, does not yet meet the threshold for “well-established use” (typically requires multiple independent RCTs over many years)
• The herb occupies an interesting position: strong Mediterranean traditional use, one impressive clinical trial, but incomplete regulatory endorsement for its most promising indication

Conditions Treated

Primary (emerging clinical evidence)

• Stage-1 hypertension (systolic 140-159 and/or diastolic 90-99 mmHg)
• Pre-hypertension (supportive)
• Borderline hypertension

Secondary

• Mild water retention (EMA/HMPC-approved traditional use)
• Hyperlipidemia (secondary finding in Susalit trial — triglyceride reduction)
• Hyperglycemia (some evidence for glucose-lowering effects)

Traditional (Mediterranean)

• Diabetes (traditional use in North Africa, Middle East)
• Fever reduction
• Urinary tract health
• General cardiovascular tonic

Mechanism of Action

ACE Inhibition

• Oleuropein and oleacein are the primary active compounds with ACE-inhibitory activity
• This provides a direct mechanistic parallel to captopril and other pharmaceutical ACE inhibitors
• The ACE inhibition explains the clinical non-inferiority to captopril observed in the Susalit trial
• Potency is significantly lower than pharmaceutical ACE inhibitors on a per-molecule basis, but achieved at the doses used in clinical trials

Vasodilation

• Oleuropein and its metabolites relax vascular smooth muscle
• Calcium channel blocking activity reported in preclinical studies
• Enhancement of nitric oxide bioavailability

Antioxidant

• Oleuropein is a potent polyphenol antioxidant
• Reduces oxidative stress in vascular endothelium
• Protects LDL from oxidation (anti-atherogenic)
• Olive leaf has one of the highest ORAC values among Mediterranean plant materials

Anti-inflammatory

• Reduces vascular inflammation markers
• Inhibits NF-kB pathway (in preclinical models)
• May contribute to long-term vascular protection

Metabolic Effects

• Improves insulin sensitivity (some evidence)
• Lowers triglycerides (observed in Susalit trial)
• May reduce fasting blood glucose

Key Active Constituents

• Oleuropein: Major secoiridoid glycoside; 16-24% in dried leaf extract (EFLA 943); ACE inhibitor, antioxidant
• Oleacein: Potent ACE inhibitor and antioxidant
• Hydroxytyrosol: Metabolite of oleuropein; strong antioxidant
• Oleanolic acid and maslinic acid: Triterpenes with anti-inflammatory activity
• Luteolin and apigenin: Flavonoids with additional vascular protective effects

Clinical Evidence Summary

Landmark Trial: Susalit et al. 2011

[Source: pubmed.ncbi.nlm.nih.gov/21036583/]

Twin Study: Perrinjaquet-Moccetti et al. (2008)

• Randomized crossover study in borderline hypertensive monozygotic twins
• Olive leaf extract reduced blood pressure significantly
• Twin design provides powerful genetic control [Source: onlinelibrary.wiley.com/doi/abs/10.1002/ptr.2455]

Lockyer et al. (2017)

• Randomized, double-blind, placebo-controlled trial
• Phenolic-rich olive leaf extract
• Modest but significant reduction in blood pressure and inflammatory markers
• Also improved lipid profile [Source: link.springer.com/article/10.1007/s00394-016-1188-y]

Meta-Analyses

Hassanein et al. (2025)

• Systematic review and meta-analysis of olive leaf extract for blood pressure in pre-hypertensive and hypertensive individuals
• Supported efficacy for blood pressure reduction [Source: pubmed.ncbi.nlm.nih.gov/40325976/]

Ismail et al. (2021)

• Systematic review and meta-analysis of olive leaf extract on cardiometabolic profile
• Found significant reductions in SBP and DBP
• Pooled data from 3 eligible studies (n=248)
• Also noted improvements in lipid parameters [Source: pubmed.ncbi.nlm.nih.gov/33868820/]

Lockyer et al. (2022)

• Meta-analysis of olive leaf extract effects on cardiovascular risk factors
• Confirmed modest but consistent blood pressure reductions [Source: pmc.ncbi.nlm.nih.gov/articles/PMC9585795/]

Evidence Limitations

• Total RCT evidence base is still relatively small (hundreds, not thousands of participants)
• Most studies are short-term (8-12 weeks)
• Long-term cardiovascular outcome data are completely absent
• Head-to-head comparison is against captopril (not the most commonly used first-line antihypertensive today)
• Standardization varies between studies (EFLA 943 vs other extracts)

European vs US/Anglophone Consensus

Safety Profile

Contraindications

• Known hypersensitivity to Olea europaea or Oleaceae family
• Caution in patients with existing hypotension
• Caution in patients with diabetes (potential additive hypoglycemic effect)

Drug Interactions

• Antihypertensives: Additive blood pressure-lowering effect; risk of excessive hypotension when combined with ACE inhibitors, ARBs, calcium channel blockers, beta-blockers, or diuretics
• Anticoagulants/Antiplatelets: May increase bleeding risk (limited evidence)
• Hypoglycemic agents: May potentiate blood glucose lowering effects of insulin and oral hypoglycemic drugs; risk of hypoglycemia
• Diuretics: Additive diuretic effect (olive leaf has mild diuretic properties)

Side Effects

• Generally well tolerated in clinical trials
• Mild and infrequent adverse effects reported:
  • GI discomfort (nausea, stomach upset) — especially on empty stomach
  • Coughing (reported in some studies)
  • Vertigo/dizziness
  • Headache
• No serious adverse events reported in clinical trials

Pregnancy and Lactation

• Not recommended — insufficient safety data
• No human studies in pregnancy or lactation
• EMA/HMPC: should only be used in adults; safety in pregnancy/lactation not established
• Traditional Mediterranean use does not provide adequate safety documentation

Clinical Dosage

Key points:

• Oleuropein content varies enormously between products (5-25% of extract weight)
• The EFLA 943 extract used in the Susalit trial is the best-characterized preparation
• Olive leaf extract is NOT the same as olive oil or olive fruit extract — the leaf has much higher oleuropein concentrations
• Blood pressure should be monitored when initiating olive leaf extract, especially in patients on antihypertensive medications

Sources

• EMA/HMPC Assessment Report on Olea europaea L., folium (Final and Draft versions)
• EMA European Union Herbal Monograph on Olea europaea L., folium
• Susalit E et al. Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: Comparison with Captopril. Phytomedicine. 2011;18(4):251-258. [PubMed: 21036583]
• Perrinjaquet-Moccetti T et al. Food supplementation with an olive (Olea europaea L.) leaf extract reduces blood pressure in borderline hypertensive monozygotic twins. Phytother Res. 2008;22(9):1239-1242.
• Lockyer S et al. Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: a randomised controlled trial. Eur J Nutr. 2017;56(4):1421-1432.
• Ismail MA et al. Olive leaf extract effect on cardiometabolic profile among adults with prehypertension and hypertension: a systematic review and meta-analysis. PeerJ. 2021;9:e11173. [PubMed: 33868820]
• Hashmi MA et al. Traditional Uses, Phytochemistry, and Pharmacology of Olea europaea (Olive). Evid Based Complement Alternat Med. 2015;2015:541591.
• Alternative Medicine Review. Olive Leaf Monograph. 2009;14(1):62-66.

Connections

• Compare with Garlic for another herb with modest antihypertensive effects
• Compare with Hawthorn for a more established cardiovascular phytomedicine in the European tradition