´ The vascular endothelium is the inner layer (monocellular) of the blood vessels, the one in contact with the blood.
´ Functions:
´ Keeps the blood inside the blood vessels
´ Regulation of the vascular permeability
´ Molecular filter (exchange of nutrients)
´ Regulation of the interaction between the vessel wall / leucocytes, platelets
´ Regulation of the vasomotion: can liberate nitric oxide(NO) which provokes vasodilatation
´ The major cardiovascular pathologies like atherosclerosis, hypertension, diabetes are characterized by the dysfunction of the endothelial cells (often oxidative stress) with a reduction of the dependant relaxations of the endothelium.
Endo- thelium
Smooth Muscle
cells
Control: • Only 3 out of 10 patients with antihypertensive treatments1 are monitored on the
target values (<140/90 mmHg)
• > 2, the number of antihypertensive drugs needed to reach the target BP, in most of the clinical studies
Low treatment compliance (bad adherence to treatment): § Side effects/ cost of treatment / dosage § 1 patient out of 2 stops the antihypertensive treatment after 3 years2
§ Only 1 patient out of 5 resorting to specialized medical care for a resistant hypertension has been found to take all prescribed medicines during a test held in the Netherlands (Sympathy Study).
Poorly-controlled Hypertension
1. Wolf-Maier et al. 2004 2. Van Wijk et al. 2005
Badly controlled hypertension increases the risk of stroke, myocardial infarctions, auricular fibrillation, heart failure or kidney disease
Consumption of olive oil polyphenols contributes to the
protection of LDL particles from oxidative damage ´ The Panel concludes that a cause and effect relationship has been
established between the consumption of olive oil polyphenols (standardized by their content of hydroxytyrosol and its derivatives) and protection of LDL particles from oxidative damage.
´ The Panel considers that in order to bear the claim, 5 mg of hydroxytyrosol and its derivatives (e.g. oleuropein complex and tyrosol) should be consumed daily.
Tensiofytol Mode of action Focus on an endothelial cell :
Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension. Moreno-luna et al. Am. J. Hypertension , dec. 2012 ,
Efficiency + Mode of action
SBP= Systolic Blood Pressure DBP=Diastolic Blood Pressure Moreno-luna et al. Am. J. Hypertension , dec. 2012 ,
Baseline after 4 months Mediterranean diet: Average Systolic Blood Pressure (SBP) 134,1 mmHg, average Diastolic Blood Pressure (DBP) 84.6 mmHg
Results
1. Decrease SBP: -7,9 mmHg and DBP -6,7 mmHg, p< 0.01 vs. Baseline
2. Ox- LDL = - 28 μg/L p < 0.01
3. CRP = - 1.9 mg/l p < 0.001
4. Improvement of endothelial function; flexibility of the blood vessel wall. p < 0.001
´ Increase in NO metabolites
Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension. Moreno-luna et al. Am. J. Hypertension , dec. 2012 ,
60ml VOO(30mg Polyphenols): 134.1mmHg à 126.2mmHg – 7.9mmHg p< 0.01
Efficiency + Mode of action
Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension:
´ Baseline average SBP: 149.3 ±5.58mmHg group olive leaf extract and 148.4 ±5.56mmHg group Captopril; Baseline average DBP: 93.9 ±4.51and 93.8 ±4.88mmHg respectively
´ Treatment:
500 mg leaf extract à 100 mg oleuropein (OE) 2x/d vs. 12.5 – 25mg Captopril 2x/d.
´ Captopril: the 1st inhibitor of angiotensin-converting enzyme (ACE)
´ Duration: 2 months
Efficiency
Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension:
´ As efficient as Captopril (50mg/day) on the decrease of SBP and DBP
´ Significant reduction of triglycerides: -23% (p<0.01)
´ No effect on the triglycerides in the group of Captopril
1000mg OLE (200 OE): 149mmHg à 137.8 mmHg – 11.5mmHg
Efficiency
Results – Blood pressure
-35 %
Ischemic heart disease
Lethal Cerebrovascular accident
-50 %
No statistical difference measured on the side effects between the treated group and placebo
1x/day N=50 patients with metabolic syndrome
Efficiency 10mg Hydroxytyrosol
Systolic Blood Pressure (mmHg)
Diastolic Blood Pressure (mmHg)
> Decrease of the cardiovascular risk LLewington S et al., Lancet. 2002;360:1903-1913
Meta-analysis on 61 observational studies (on 1 million adult patients)
7%
Decrease of 2 mmHg Coronary artery disease Systolic Blood pressure
10% Decrease of mortality due to a stroke
Randomized studies on elderly subjects with hypertension and treated since at least 5 years with beta blockers and diuretics N =62 : 31 Hypertensive + 31 Normotensive / 42 women 20 men Average age 84 years Treatment: 60g/day Virgin olive oil (VOO) vs. Sunflower oil Duration: 1 month treatment – 1 month wash out – Switch – 1 month treatment
Olive oil, in combination with antihypertensive drugs Perona 2004 Clinical Nutrition (2004)
Virgin olive oil reduces blood pressure in hypertensive elderly subjects
Efficiency
Results: Virgin olive oil (VOO), reduces the BP and normalizes the BP (136 mmHg) vs. Sunflower oil (150 ±8 mmHg). Virgin olive oil (VOO) reduced the total Cholesterol and the LDL-Cholesterol in the Normotensive patients (P<0:01) vs. Sunflower oil
Olive oil, in combination with antihypertensive drugs
Perona 2004 Clinical Nutrition (2004)
Virgin olive oil reduces blood pressure in hypertensive elderly subjects
VOO: 150 mmHg à 136 mmHg – 14mmHg P<0.01 vs Sunflower oil
VOO: Virgin Olive Oil SO: Sunflower oil
SIGNIFICANT ACTION ON THE BLOOD PRESSURE IN ADDITION TO AN ANTIHYPERTENSIVE TREATMENT!
7447 subjects during 4,8 years a. Mediterranean diet + Virgin olive oil: 1 liter/week b. Mediterranean diet + Nuts: 30g/ day (walnuts, hazelnuts, almonds) c. Control: low fat diet
PREDIMED Study : 7447 subjects have followed one of these 3 diets during 4,8 years9
Number of myocardial infarctions, strokes and deaths due to cardiovascular causes :
Inc
ide
nce
of t
he c
ard
iova
scul
ar e
vent
s -30% cardiovascular events (p<0,003)
Control group Mediterranean diet + nuts Mediterranean diet + Extra Virgin olive oil
Years
The Mediterranean diet caused reductions in oxidized LDL cholesterol, along with improvements in several other heart disease risk factors
Effect of a Traditional Mediterranean Diet on Lipoprotein Oxidation. JAMA Internal Medicine, 2007.
372 individuals from the PREDIMED study who were at a high cardiovascular risk were assessed after 3 months
VOO: Virgin Olive Oil
1 year intervention with two Mediterranean diets (Med-diet) could decrease blood pressure (BP) due to a high polyphenol consumption N= 200 high CV risk (elderly) 1 year EVOO vs. Med-nuts / randomized controlled clinical trial Measure: BP, NO, Total Polyphenol Excretion (TPE) Systolic and diastolic BP decreased significantly after a one-year dietary intervention with Med-EVOO and Med-nuts. These changes were associated with a significant increase in TPE and plasma NO. Additionally, a significant positive correlation was observed between changes in urinary TPE, a biomarker of TP intake, and in plasma NO.
Olive oil Medina Remon 2015
Effects of total dietary polyphenols on plasma nitric oxide and blood pressure in a high cardiovascular risk cohort.
The PREDIMED randomized trial
This was a three-arm randomized trial in 418 non-diabetic subjects aged 55–80 years recruited in one center Participants were randomly assigned to education on a low-fat diet (control group) or to one of two MedDiets, supplemented with either free virgin olive oil (1 liter/week) or nuts (30 g/day), for 4 years
diabetes incidence reduced by 52%
Hydroxytyrosol Reduction in Incidence of T2DM with Mediterranean Diet Results of the PREDIMED-Reus nutrition intervention randomized trial
A = olive oil C = control
P<0.047
Action olive oil : Inflammation Marker and Endothelial Function
• 30 studies / 3106 patients § Dosage: 1 – 50 mg /day • ê significant CRP (C-Reactive Protein)(p<0.0001) n=15 studies • ê significant IL-6 (Interleukin-6) (p<0.04 • Improvement of the endothelial function (NO)/ (p<0.002) n=8
• é flow-mediated dilation(FMD )
Olive oil exerts beneficial effects on the endothelial functions and on the inflammation markers à contributes to the cardiovascular protection linked to the Mediterranean diet
Meta-analyse – Olive oil Schwingshackl 2015 nutrients Effects of Olive Oil on Markers of Inflammation and Endothelial
Function—A Systematic Review and Meta-Analysis
Mode of action
• Improvement of the endothelial function (NO)/ n=8 studies 335 patients • é flow-mediated dilation (FMD) p<0.002
Meta-analyse – Olive oil Schwingshackl 2015 nutrients Effects of Olive Oil on Markers of Inflammation and Endothelial
Regular BP > 130/80 mmHg In pre- or post-menopause
n Family history of hypertension n high cholesterol level n Overweight n Sedentary n Keen on salt - prepared dishes
n Metabolic syndrome
To whom advice early natural medical care? Measure the BP (mmHg)
Optimal BP Pre-hypertension Normal HT HT stage 1
Prevention advice
Control 1/year
Symptomatic Asymptomatic Symptomatic
Lifestyle
Control every 6 months Check regularly
Study of associated CVRF + evaluation of complications
Medical evaluation
Study of associated CVRF + evaluation of complications +
Etiology
Pharmacological
treatment
Dietary supplement targeted standardized at :
n 100 mg oleuropein
n 20 mg hydroxytyrosol
Dietary supplement targeted*
standardized at :
n 100 mg oleuropein
n 20 mg hydroxytyrosol
*If the targeted blood pressure remains difficult to reach with the pharmacologocal treatment and lifestyle
EndoPat 2000, Itamar
Reactive Ischemia Hyperemia (RIH)
Morten and Vidiendal Olsen Evaluation of endothelial function by peripheral arterial tonometry and relation with the nitric oxide pathway. Nitric Oxide 2014
Left arm
Right arm
6 minutes rest 5 minutes of ischemia
6 minutes post ischemia
EndoPat 2000 system
2 caps (100 mg oleuropéine
20 mg hydroxytyrosol)
T0 T 1 hour
On going study at ULG/Cardio service : vasodilating effect of Tensiofytol evaluated with the EndoPat
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