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Life Extension Magazine March 2012

Olive Leaf Extract

Blood pressure in early adulthood, hypertension in middle age, and future cardiovascular disease mortality: HAHS (Harvard Alumni Health Study).

OBJECTIVES: We sought to examine the association of early adulthood blood pressure with cardiovascular disease (CVD) mortality, while accounting for middle-age hypertension. BACKGROUND: Elevated blood pressure in middle age is an established CVD risk factor, but evidence for association with measurements earlier in life is sparse. METHODS: The HAHS (Harvard Alumni Health Study) is a cohort study of 18,881 male university students who had their blood pressure measured at university entry (1,914 to 1,952; mean age 18.3 years) and who responded to a questionnaire mailed in either 1962 or 1966 (mean age 45.8 years) in which physician-diagnosed hypertension status was reported. Study members were subsequently followed for mortality until the end of 1998. RESULTS: Following adjustment for age, body mass index, smoking, and physical activity at college entry, compared with men who were normotensive according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria (<120/<80 mm Hg), there was an elevated risk of coronary heart disease (CHD) mortality (1,917 deaths) in those who were pre-hypertensive (120 to 139/80 to 89 mm Hg) (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.07 to 1.36), stage 1 (140 to 159/90 to 99 mm Hg) (HR: 1.46; 95% CI: 1.25 to 1.70), and stage 2 hypertensive (≥160/≥100 mm Hg) (HR: 1.89; 95% CI: 1.46 to 2.45), incremental across categories (p(trend) < 0.001). After additionally accounting for middle-age hypertension, estimates were somewhat attenuated, but the pattern remained. Similar associations were apparent for total and CVD mortality, but not stroke mortality. CONCLUSIONS: Higher blood pressure in early adulthood was associated with elevated risk of all-cause mortality, CVD, and CHD, but not stroke, several decades later. Effects largely persisted after taking into account mediation by middle-age hypertension. Thus, the long-term benefits of blood pressure lowering in early adulthood are promising, but supporting trial data are required.

J Am Coll Cardiol. 2011 Nov 29;58(23):2396-403

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

“The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure” provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician’s judgment remains paramount.

JAMA. 2003 May 21;289(19):2560-72

Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: comparison with Captopril.

A double-blind, randomized, parallel and active-controlled clinical study was conducted to evaluate the anti-hypertensive effect as well as the tolerability of Olive leaf extract in comparison with Captopril in patients with stage-1 hypertension. Additionally, this study also investigated the hypolipidemic effects of Olive leaf extract in such patients. It consisted of a run-in period of 4 weeks continued subsequently by an 8-week treatment period. Olive (Olea europaea L.) leaf extract (EFLA® 943) was given orally at the dose of 500 mg twice daily in a flat-dose manner throughout the 8 weeks. Captopril was given at the dosage regimen of 12.5 mg twice daily at start. After 2 weeks, if necessary, the dose of Captopril would be titrated to 25 mg twice daily, based on subject’s response to treatment. The primary efficacy endpoint was reduction in systolic blood pressure (SBP) from baseline to week-8 of treatment. The secondary efficacy endpoints were SBP as well as diastolic blood pressure (DBP) changes at every time-point evaluation and lipid profile improvement. Evaluation of BP was performed every week for 8 weeks of treatment; while of lipid profile at a 4-week interval. Mean SBP at baseline was 149.3±5.58 mmHg in Olive group and 148.4±5.56 mmHg in Captopril group; and mean DBPs were 93.9±4.51 and 93.8±4.88 mmHg, respectively. After 8 weeks of treatment, both groups experienced a significant reduction of SBP as well as DBP from baseline; while such reductions were not significantly different between groups. Means of SBP reduction from baseline to the end of study were -11.5±8.5 and -13.7±7.6 mmHg in Olive and Captopril groups, respectively; and those of DBP were -4.8±5.5 and -6.4±5.2 mmHg, respectively. A significant reduction of triglyceride level was observed in Olive group, but not in Captopril group. In conclusion, Olive (Olea europaea) leaf extract, at the dosage regimen of 500 mg twice daily, was similarly effective in lowering systolic and diastolic blood pressures in subjects with stage-1 hypertension as Captopril, given at its effective dose of 12.5-25 mg twice daily.

Phytomedicine. 2011 Feb 15;18(4):251-8

Food supplementation with an olive (Olea europaea L.) leaf extract reduces blood pressure in borderline hypertensive monozygotic twins.

Hypertension is a harmful disease factor that develops unnoticed over time. The treatment of hypertension is aimed at an early diagnosis followed by adequate lifestyle changes rather than pharmacological treatment. The olive leaf extract EFLA943, having antihypertensive actions in rats, was tested as a food supplement in an open study including 40 borderline hypertensive monozygotic twins. Twins of each pair were assigned to different groups receiving 500 or 1,000 mg/day EFLA943 for 8 weeks, or advice on a favourable lifestyle. Body weight, heart rate, blood pressure, glucose and lipids were measured fortnightly. Blood pressure changed significantly within pairs, depending on the dose, with mean systolic differences of < or =6 mmHg (500 mg vs control) and < or =13 mmHg (1,000 vs 500 mg), and diastolic differences of < or =5 mmHg. After 8 weeks, mean blood pressure remained unchanged from baseline in controls (systolic/diastolic: 133 +/- 5/77 +/- 6 vs 135 +/- 11/80 +/- 7 mmHg) and the low-dose group (136 +/- 7/77 +/- 7 vs 133 +/- 10/76 +/- 7), but had significantly decreased for the high dose group (137 +/- 10/80 +/- 10 vs 126 +/- 9/76 +/- 6). Cholesterol levels decreased for all treatments with significant dose-dependent within-pair differences for LDL-cholesterol. None of the other parameters showed significant changes or consistent trends. Concluding, the study confirmed the antihypertensive and cholesterol-lowering action of EFLA943 in humans.

Phytother Res. 2008 Sep;22(9):1239-42

Olea europaea leaf extract exerts L-type Ca(2+) channel antagonistic effects.

ETHNOPHARMACOLOGICAL RELEVANCE: In Southern Europe Olea europaea leafs are known as a folk remedy for hypertension. Cardiovascular diseases are still the leading causes of morbidity and mortality in industrialized countries with hypertension being one of the main risk factors. AIM OF THE STUDY: We investigated effects of a commercial Olea europaea leaf extract (OLE) on isolated hearts and cultured cardiomyocytes. MATERIALS AND METHODS: Isolated rabbit hearts were perfused according to the Langendorff technique and connected to a 256-channel epicardial mapping system. Voltage clamp experiments were performed in cultured neonatal rat cardiomyocytes using a perforated-patch technique. RESULTS: OLE caused a concentration-depended decrease in systolic left ventricular pressure and heart rate as well as an increase in relative coronary flow and a slight, but not significant prolongation of PQ-time. There were no significant changes between the groups in the activation-recovery interval and its dispersion, total activation time, peak-to-peak amplitude, percentage of identical breakthrough-points and similar vectors of local activation. Voltage clamp experiments in cultured neonatal rat cardiomyocytes showed a significant decrease in maximum I(Ca,L) by OLE which was reversible upon wash-out. CONCLUSIONS: OLE suppresses the L-type calcium channel directly and reversibly. Our findings might help to understand the traditional use of OLE in the treatment of cardiovascular disease.

J Ethnopharmacol. 2008 Nov 20;120(2):233-40

Blood pressure lowering effect of olive is mediated through calcium channel blockade.

Olive (Olea europea) is used in traditional medicine as a remedy for hypertension. The aqueous-methanolic crude extract of O. europea fruit (OeF.Cr) was studied in anaesthetized rats and its possible mechanism was elucidated using isolated cardiovascular preparations. Intravenous administration of OeF.Cr produced a dose-dependent (30-100 mg/kg) fall in arterial blood pressure in normotensive anaesthetized rats. This effect remained unaltered in atropinized animals. In the in vitro studies OeF.Cr (0.1-3.0 mg/ml) inhibited spontaneously beating guinea-pig atria. Moreover, it relaxed K+ and/or phenylephrine-induced contractions of rabbit aortic preparations over a dose range of 0.1-3.0 mg/ml, suggesting calcium channel blockade (CCB). The CCB effect was confirmed when pretreatment of the vascular preparations with OeF.Cr produced a dose-dependent rightward shift of the Ca2+ dose-response curves, similar to verapamil. These results suggest that the blood pressure lowering effect of olive is mediated through CCB, justifying its use in hypertension.

Int J Food Sci Nutr. 2005 Dec;56(8):613-20

Oleuropein, the bitter principle of olives, enhances nitric oxide production by mouse macrophages.

The Mediterranean diet, rich in fresh fruits and vegetables, has been associated with a lower incidence of cardiovascular disease and cancer, partly because of its high proportion of bioactive compounds such as vitamins, flavonoids and polyphenols. The major lipid component of such diet is the drupe-derived olive oil, that can be distinguished from other seed oils for the peculiar composition of its non-triglyceride fraction. In fact, several minor components, including polyphenols, grant the oil its particular taste and aroma. Oleuropein, the most abundant among these components, has been shown to be a potent antioxidant endowed with antiinflammatory properties. We investigated the effects of oleuropein on NO release in cell culture and its activity toward nitric oxide synthase (iNOS) expression. The results show that oleuropein dose-dependently enhance nitrite production in LPS-challenged mouse macrophages. This effect was blocked by the iNOS inhibitor L-NAME, indicating increased iNOS activity. Also, Western blot analysis of cell homogenates show that oleuropein increases iNOS expression in such cells. Taken together, our data suggest that, during endotoxin challenge, oleuropein potentiates the macrophage-mediated response, resulting in higher NO production, currently believed to be beneficial for cellular and organismal protection.

Life Sci. 1998;62(6):541-6