AOR guarantees that no ingredients not listed on the label have been added to the product. Contains no wheat, gluten, corn, nuts, dairy, soy, eggs, fish or shellfish.

Suggested Use
Take one capsule twice a day, or as directed by a qualified health care practitioner.

Main Applications
As reported by literature:
• Chronic fatigue.
• Flu and colds.
• Herpes.
• HIV.
• Rheumatoid arthritis.
• Fungus and yeast infections.
• Bacterial infections.
• Skin conditions.
• Tropical illness.
• Diabetes.

Source
Obtained from specific parts of the olive tree leaves (Olea europea).

Pregnancy / Nursing
No studies have been conducted. Best to avoid.

Cautions
Must be aware of "die-off" reaction, due to the sudden release of toxins.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Copyright © 2005, Advanced Orthomolecular Research

Chemistry
The pharmacologically active constituents in olive leaves are secoridoids, such as: oleuropein, oleuroside, ligstroside. Other ingredients include flavonoids, apigenin, caffeic acids and triterpenes. Oleuropein, a bitter glucoside found in highest concentrations in the leaves, has been well researched. It is responsible for many of the biological effects of olive leaf extract, and is readily absorbed and bioavailable.

Pharmacological properties / Clinical applications

Antihypertensive: Olive extracts have been found to lower blood pressure. Oleuropein possesses a vasodilator (blood vessel relaxing) effect. Moreover, a recent study has found that the aqueous extract of olive leaves inhibited Angiotensin converting enzyme (ACE), an enzyme that converts angiotensin I to angiotensin II. Angiotensin II is a potent vasoconstrictor.

Antithrombosis: The phenolic compound 3,4-di-hydrophenyl ethanol inhibited aggregation of platelet and production of thromboxane A2 (a stimulator of platelet aggregation with vasoconstrictor activity).

Prevention of development of atherosclerotic lesions: The secoridoid and phenolic compounds were found to protect vascular endothelium cells from damage. Olive extracts have been found to prevent the oxidation of lipids and of low density lipoprotein (LDL) cholesterol, which leads to plaque formation.

Antioxidant activity: Caffeic acid and oleuropein were found to inhibit iron toxicity in rat hepatocytes by their antioxidant activity through the scavenging of superoxide radical. The compounds of olive leaf extracts have been shown to be more potent antioxidants than BHT or vitamin E.

Hypoglycemic effect: Oleuropein has a hypoglycemic effect possibly due to the potentiation of glucose-induced insulin release and/or increased peripheral glucose uptake.

Immune regulation: Olive leaf extracts have anti-inflammatory effects, and are able to increase the functional activity of important immune cells known as macrophages.

Antimicrobial Activity

1. Antibacterial: The extracts of olive leaf have potent antimicrobial activities against bacteria, fungi and mycoplasma. Oleuropein has been shown to inhibit growth and the production of enterotoxin B by Staphylococcus. Oleuropein also inhibits the growth of Bacillus cereus, E. coli, pseudomar, Bacillus subtilis, etc.

2. Antiviral: Olive leaf extract (calcium elenolate) eliminates the viruses by interfering with certain amino acid production processes. The interference stops the virus from shedding, budding, or assembling at the cell membrane. Laboratory tests suggest that the compound has the ability to penetrate infected host cells and irreversibly inhibit viral replication. Oleuropein possesses antiviral activity against a number of viruses including parainfluenza 3, herpes, influenza A, polio, etc.
AIDS patients have begun to use olive leaf extract to help strengthen their immune system, relieve chronic fatigue, boost the effects of anti-HIV medications and help with HIV-associated infections. In vitro studies have found that the compounds of olive leaf extracts inhibit acute HIV-infection and cell-to-cell transmission, and block HIV replication, with no effect on uninfected target cells. The compounds have also been shown to reverse many of the changes in gene expression caused by HIV infection.

References

Furneri PM, Marino A, Saija A, Uccella N, Bisignano G. "In vitro antimycoplasmal activity of oleuropein." Int J Antimicrob Agents. 2002 Oct; 20(4): 293-6.

Ma SC, He ZD, Deng XL, But PP, Ooi VE, Xu HX, Lee SH, Lee SF. "In vitro evaluation of secoiridoid glucosides from the fruits of Ligustrum lucidum as antiviral agents." Chem Pharm Bull (Tokyo). 2001 Nov; 49(11): 1471-3.

Bisignano G, Tomaino A, Lo Cascio R, Crisafi G, Uccella N, Saija A. "On the in-vitro antimicrobial activity of oleuropein and hydroxytyrosol." J Pharm Pharmacol. 1999 Aug; 51(8): 971-4.

Aziz NH, Farag SE, Mousa LA, Abo-Zaid MA. "Comparative antibacterial and antifungal effects of some phenolic compounds." Microbios. 1998; 93(374): 43-54.

Tassou CC, Nychas GJ. "Inhibition of Salmonella enteritidis by oleuropein in broth and in a model food system." Lett Appl Microbiol. 1995 Feb; 20(2): 120-4.

Tranter HS, Tassou SC, Nychas GJ. "The effect of the olive phenolic compound, oleuropein, on growth and enterotoxin B production by Staphylococcus aureus." J Appl Bacteriol. 1993 Mar; 74(3): 253-9.

Tassou CC, Nychas GJ, Board RG. "Effect of phenolic compounds and oleuropein on the germination of Bacillus cereus T spores." Biotechnol Appl Biochem. 1991 Apr; 13(2): 231-7.

Fleming HP, Walter WM Jr, Etchells JL. "Antimicrobial properties of oleuropein and products of its hydrolysis from green olives." Appl Microbiol. 1973 Nov; 26(5): 777-82.

Gonzalez M, Zarzuelo A, Gamez MJ, Utrilla MP, Jimenez J, Osuna I. "Hypoglycemic activity of olive leaf." Planta Med 1992 Dec; 58(6): 513-5.

Cherif S, Rahal N, Haouala M, Hizaoui B, Dargouth F, Gueddiche M, Kallel Z, Balansard G, Boukef K. "A clinical trial of a titrated Olea extract in the treatment of essential arterial hypertension." J Pharm Belg 1996 Mar-Apr; 51(2): 69-71.

Zarzuelo A, Duarte J, Jimenez J, Gonzalez M, Utrilla MP. "Vasodilator effect of olive leaf." Planta Med 1991 Oct; 57(5): 417-9.

Fehri B, Aiache JM, Memmi A, Korbi S, Yacoubi MT, Mrad S, Lamaison JL. "Hypotension, hypoglycemia and hypouricemia recorded after repeated administration of aqueous leaf extract of Olea europaea L." J Pharm Belg 1994 Mar-Apr; 49(2): 101-8.

The activity of oleuropein, a phenolic glycoside contained in olive oil, was investigated in vitro against Mycoplasma hominis, Mycoplasma fermentans, Mycoplasma pneumoniae and Mycoplasma pirum. Oleuropein inhibited mycoplasmas at concentrations from 20 to 320 mg/l. The MICs of oleuropein to M. pneumoniae, M. pirum, M. hominis and M. fermentans were 160, 320, 20 and 20 mg/l, respectively.


In vitro evaluation of secoiridoid glucosides from the fruits of Ligustrum lucidum as antiviral agents.
Chem Pharm Bull (Tokyo). 2001 Nov; 49(11): 1471-3.
Ma SC, He ZD, Deng XL, But PP, Ooi VE, Xu HX, Lee SH, Lee SF.

Six secoiridoid glucosides, lucidumoside C (1), oleoside dimethylester (2), neonuezhenide (3), oleuropein (4), ligustroside (5) and lucidumoside A (6), isolated from the fruits of Ligustrum lucidum (Oleaceae), were examined in vitro for their activities against four strains of pathogenic viruses, namely herpes simplex type I virus (HSV-1), influenza type A virus (Flu A), respiratory syncytial virus (RSV) and parainfluenza type 3 virus (Para 3). Antiviral activities were evaluated by the cytopathic effect (CPE) inhibitory assay. The purpose was to check if the antioxidative potency of these glucosides correlated with their antiviral potency. Results showed that none of the glucosides had any significant activity against HSV-1 and Flu A. Oleuropein, however, showed significant antiviral activities against RSV and Para 3 with IC50 value of 23.4 and 11.7 microg/ml, respectively. Lucidumoside C, oleoside dimethylester and ligustroside showed potent or moderate antiviral activities against Para 3 with IC50 values of 15.6-20.8 microg/ml. These results also documented that the anti-oxidative potency of these secoiriodoid glucosides was not directly related to their antiviral effects.


On the in-vitro antimicrobial activity of oleuropein and hydroxytyrosol.
J Pharm Pharmacol. 1999 Aug; 51(8): 971-4.
Bisignano G, Tomaino A, Lo Cascio R, Crisafi G, Uccella N, Saija A.

Secoiridoides (oleuropein and derivatives), one of the major classes of polyphenol contained in olives and olive oil, have recently been shown to inhibit or delay the rate of growth of a range of bacteria and microfungi but there are no data in the literature concerning the possible employment of these secoiridoides as antimicrobial agents against pathogenic bacteria in man. In this study five ATCC standard bacterial strains (Haemophilus influenzae ATCC 9006, Moraxella catarrhalis ATCC 8176, Salmonella typhi ATCC 6539, Vibrio parahaemolyticus ATCC 17802 and Staphylococcus aureus ATCC 25923) and 44 fresh clinical isolates (Haemophilus influenzae, eight strains, Moraxella catarrhalis, six strains, Salmonella species, 15 strains, Vibrio cholerae, one strain, Vibrio alginolyticus, two strains, Vibrio parahaemolyticus, one strain, Staphylococcus aureus, five penicillin-susceptible strains and six penicillin-resistant strains), causal agents of intestinal or respiratory tract infections in man, were tested for in-vitro susceptibility to two olive (Olea europaea) secoiridoides, oleuropein (the bitter principle of olives) and hydroxytyrosol (derived from oleuropein by enzymatic hydrolysis and responsible for the high stability of olive oil). The minimum inhibitory concentrations (MICs) calculated in our study are evidence of the broad antimicrobial activity of hydroxytyrosol against these bacterial strains (MIC values between 0.24 and 7.85 microg mL(-1) for ATCC strains and between 0.97 and 31.25 microg mL(-1) for clinically isolated strains). Furthermore oleuropein also inhibited (although to a much lesser extent) the growth of several bacterial strains (MIC values between 62.5 and 500 microg mL(-1) for ATCC strains and between 31.25 and 250 microg mL(-1) for clinical isolates); oleuropein was ineffective against Haemophilus influenzae and Moraxella catarrhalis. These data indicate that in addition to the potential employment of its active principles as food additives or in integrated pest-management programs, Olea europaea can be considered a potential source of promising antimicrobial agents for treatment of intestinal or respiratory tract infections in man.

Comparative antibacterial and antifungal effects of some phenolic compounds.
Microbios. 1998; 93(374): 43-54.
Aziz NH, Farag SE, Mousa LA, Abo-Zaid MA.

The antimicrobial potential of eight phenolic compounds isolated from olive cake was tested against the growth of Escherichia coli, Klebsiella pneumoniae, Bacillus cereus, Aspergillus flavus and Aspergillus parasiticus. The phenolic compounds included p-hydroxy benzoic, vanillic, caffeic, protocatechuic, syringic, and p-coumaric acids, oleuropein and quercetin. Caffeic and protocatechuic acids (0.3 mg/ml) inhibited the growth of E. coli and K. pneumoniae. The same compounds apart from syringic acid (0.5 mg/ml) completely inhibited the growth of B. cereus. Oleuropein, and p-hydroxy benzoic, vanillic and p-coumaric acids (0.4 mg/ml) completely inhibited the growth of E. coli, K. pneumoniae and B. cereus. Vanillic and caffeic acids (0.2 mg/ml) completely inhibited the growth and aflatoxin production by both A. flavus and A. parasiticus, whereas the complete inhibition of the moulds was attained with 0.3 mg/ml p-hydroxy benzoic, protocatechuic, syringic, and p-coumaric acids and quercetin.


Inhibition of Salmonella enteritidis by oleuropein in broth and in a model food system.
Lett Appl Microbiol. 1995 Feb; 20(2): 120-4.
Tassou CC, Nychas GJ.

The inhibitory effect of commercial 'pure' oleuropein was tested against Salmonella enteritidis in a coliform broth and in reconstituted milk (model food system). It was found that the inhibition of this organism in the broth was influenced by the initial inoculum size, the pH of the medium and the concentration of additive. The inhibition was more pronounced in samples with low pH and low inoculum size. No such inhibition was evident in the model food system.


The effect of the olive phenolic compound, oleuropein, on growth and enterotoxin B production by Staphylococcus aureus.
J Appl Bacteriol. 1993 Mar; 74(3): 253-9.
Tranter HS, Tassou SC, Nychas GJ.

The presence of low concentrations (0.1% w/v) of oleuropein, a phenolic compound extracted from olives, delayed the growth of Staphylococcus aureus in NZ amine A and brain heart infusion media modified by the addition of growth factors and glucose (NZA+ and BHI+), as indicated by changes in conductance, whilst higher concentrations (0.4-0.6% w/v) inhibited growth completely. Intermediate concentrations of oleuropein (0.2%) prevented growth in BHI+ but allowed growth to occur in NZA+ despite an extended lag phase (30 h). Concentrations of oleuropein > 0.2% inhibited growth and production of enterotoxin B in both types of media. Lower levels (0.1%) did not affect the final viable count and production of toxin in BHI+ but decreased the number of viable organisms and reduced the toxin production in NZA+ by eightfold. An increase in the concentration of oleuropein resulted in a decrease in the amount of glucose assimilated and consequently the amount of lactate produced. In addition, oleuropein prevented the secretion of a number of exoproteins. Addition of oleuropein during the exponential phase appeared to have no effect on the growth of Staph. aureus in NZA+.


Effect of phenolic compounds and oleuropein on the germination of Bacillus cereus T spores.
Biotechnol Appl Biochem. 1991 Apr; 13(2): 231-7.
Tassou CC, Nychas GJ, Board RG.

The phenolic compounds extracted from olives with ethyl acetate inhibited germination and outgrowth of Bacillus cereus T spores. Purified oleuropein, a well-characterized component of olive extract, inhibited these processes also. The addition of oleuropein and olive extracts 3 or 5 min after germination began, immediately decreased the rate of change of phase bright to phase dark spores and delayed significantly outgrowth.


Antimicrobial properties of oleuropein and products of its hydrolysis from green olives.
Appl Microbiol. 1973 Nov; 26(5): 777-82.
Fleming HP, Walter WM Jr, Etchells JL.

Oleuropein, the bitter glucoside in green olives, and products of its hydrolysis were tested for antibacterial action against certain species of lactic acid bacteria involved in the brine fermentation of olives. Oleuropein was not inhibitory, but two of its hydrolysis products, the aglycone and elenolic acid, inhibited growth of the four species of lactic acid bacteria tested. Another hydrolysis product, ß-3, 4-dihydroxyphenylethyl alcohol, was not inhibitory. The aglycone of oleuropein, and elenolic acid were much more inhibitory when the broth medium contained 5% NaCl; 150 µg of either compound per ml prevented growth of Lactobacillus plantarum. A crude extract of oleuropein, tested by paper disk bioassay, was inhibitory to 3 to 17 species of bacteria screened, none of which were lactic acid bacteria. The acid hydrolysate of the extract was inhibitory to 11 of the bacteria, which included four species of lactic acid bacteria and other gram-positive and gram-negative species. Neither crude preparation was inhibitory to growth of the seven species of yeast tested. A possible explanation is given for the previously reported observation that heating (3 min, 74 C) olives prior to brining renders them more fermentable by lactic acid bacteria. Results of a brining experiment indicated that oleuropein is degraded to antibacterial compounds when unheated olives are brined.


Hypoglycemic activity of olive leaf.
Planta Med 1992 Dec; 58(6): 513-5.
Gonzalez M, Zarzuelo A, Gamez MJ, Utrilla MP, Jimenez J, Osuna I.

The hypoglycemic activity of olive leaf was studied. Maximum hypoglycemic activity was obtained from samples collected in the winter months, especially in February. One of the compounds responsible for this activity was oleuropeoside, which showed activity at a dose of 16 mg/kg. This compound also demonstrated antidiabetic activity in animals with alloxan-induced diabetes. The hypoglycemic activity of this compound may result from two mechanisms: (a) potentiation of glucose-induced insulin release, and (b) increased peripheral uptake of glucose.


A clinical trial of a titrated Olea extract in the treatment of essential arterial hypertension
J Pharm Belg 1996 Mar-Apr; 51(2): 69-71.
Cherif S, Rahal N, Haouala M, Hizaoui B, Dargouth F, Gueddiche M, Kallel Z, Balansard G, Boukef K.

A clinical assay of Olea europaea L. aqueous extract was carried on two groups of patients suffering with essential hypertension. 12 patients consulting for the first time, 18 patients with antihypertensive treatment. Treatment based on Olea europeae L. leaf aqueous extract was given (400 ng x 4/24 h) during 3 months, after 15 days treatment based on placebo. We note for all patients a statistically significant decrease of blood pressure (p < 0.001), we didn't find any modification of biological parameters excepted a significant little decrease of glycemia and calcemia p < 0.01 and p < 0.01 respectively. We didn't find any side effect in the two groups.


Vasodilator effect of olive leaf.
Planta Med 1991 Oct; 57(5): 417-9.
Zarzuelo A, Duarte J, Jimenez J, Gonzalez M, Utrilla MP.

We studied the importance of the smooth vascular muscle endothelium in the vasodilator action of the decoction of olive (Olea europaea) leaf. The decoction caused relaxation of isolated rat aorta preparations both in the presence (IC50 1.12 +/- 0.33 mg/ml) and in the absence (IC50 1.67 +/- 0.16 mg/ml) of endothelium. The results indicate that the relaxant activity of the lyophilized decoction is independent of the integrity of the vascular endothelium. We also showed that oleuropeoside is a component responsible for vasodilator activity but, from the results, it seems likely that at least one other principle is to be found in the olive leaf which is either a vasodilator itself or else potentiates the relaxant effect of oleuropeoside.


Hypotension, hypoglycemia and hypouricemia recorded after repeated administration of aqueous leaf extract of Olea europaea L.
J Pharm Belg 1994 Mar-Apr; 49(2): 101-8.
Fehri B, Aiache JM, Memmi A, Korbi S, Yacoubi MT, Mrad S, Lamaison JL.

This study is concerned by the determination of the toxicity of an Olea europaea L.aqueous leaf extract after repeated administrations. Female and male rats were given 37.5, 75, 150, 300, 600 and 1200 mg/Kg/24h of the extract for 60 days. The results show that the drug studied induces an increase of weight growth, an hypotension, an hypoglycaemia and an hypouricaemia in treated animals.