Re: Consumption of Olive Leaf Extract Improves Cardiovascular Disease Risk Factors in Males with Prehypertension

Olive (Olea europaea, Oleaceae) Leaf Extract Cardiovascular Health Date: 08-15-2017 HC# 071731-574 Lockyer S, Rowland I, Spencer JPE, Yaqoob P, Stonehouse W. 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. The Mediterranean diet is associated with a decreased risk for cardiovascular diseases (CVDs), which is attributed to the olive (Olea europaea, Oleaceae) oil in the diet. Olive plant leaves contain higher concentrations of phenolic compounds (1450 mg total phenolics per 100 g fresh leaf) than do the fruit (110 mg per 100 g fruit) and oil (23 mg per 100 mL extra virgin olive oil). Studies suggest that olive leaf extract (OLE) decreases CVD risk through its antiatherosclerotic, hypotensive, antioxidant, anti-inflammatory, and hypocholesterolemic properties. These authors conducted a randomized, controlled, double-blind, crossover, intervention trial to examine the effect of OLE on 24-hour ambulatory blood pressure (ABP) and other vascular, lipid, and inflammatory markers in males with prehypertension. The study was conducted at Massey University's School of Food and Nutrition in Auckland, New Zealand, from May 2013 to September 2013. Subjects were recruited through newspaper advertisements and postings in shops and community buildings in the Auckland area, and flyers and posters on the university campus. Eligible subjects were prehypertensive, nonsmoking, free from chronic disease, and not taking antihypertensives, statins, or other medications or dietary supplements that would affect BP, lipids, or blood clotting. Prehypertension was described as an average systolic BP (SBP) of 121-140 mm Hg and/or average diastolic BP (DBP) of 81-90 mm Hg. The study's primary outcome was BP; secondary outcomes were vascular function, arterial stiffness, and levels of plasma lipids, glucose, insulin, fructosamine, oxidized low-density lipoprotein (oxLDL), C-reactive protein, adiponectin, cell adhesion molecules, and cytokines. The crossover study included 61 subjects aged 45.3 ± 12.7 years who were randomly assigned to consume either a liquid OLE supplement or a control twice daily for 6 weeks, followed by a 4-week washout period and then a second 6-week phase, during which the subjects consumed the alternate study product. Plant sterol- and stanol-enriched spreads and all olive-containing products were prohibited during the study. The subjects visited the clinic at baseline, after the first phase (week 6), after the washout period (week 10), and after the second phase (week 16). They were instructed to refrain from alcohol consumption and strenuous exercise the day before each visit and to eat a standard low-fat, low-phenolic meal provided to them the evening before each visit. Olive Leaf Extract Extra Strength (Comvita Limited; Paengaroa, Te Puke, New Zealand), used in the study, contains vegetable glycerin and water in a 50:50 ratio plus OLE. The dosage used in the study (10 mL twice daily with food) provided 136.2 mg oleuropein and 6.4 mg hydroxytyrosol daily. The control intervention contained vegetable glycerin and water plus food colorings and flavorings to match the OLE. At each clinic visit, the subjects underwent tests to measure pulse wave velocity (PWV), a predictor of cardiovascular mortality and morbidity, as the velocity at which pulse waves travel along the arteries is determined by the elasticity of the arterial walls. Pulse wave analysis, which measures augmentation index, an indicator of arterial stiffness, was also conducted. Body composition was assessed, BP was measured, and fasting blood samples were drawn. ABP was assessed at baseline and at weeks 6, 10, and 16 by using automated monitors, which the subjects wore for 25 hours. At baseline, all subjects had a mean daytime BP of 139/83 mm Hg, an average body mass index of 26.7 kg/m2, and above-normal total cholesterol (TC), LDL cholesterol (LDL-C), and TC/high-density lipoprotein cholesterol (HDL-C) levels. Triglyceride and HDL-C levels were within normal limits. Of the 61 enrolled subjects, 1 moved and dropped out of the study. The remaining 60 subjects completed the study; compliance rates were 70.19% for the OLE intervention and 74.54% for the control intervention. Mild adverse effects, such as acne and stomach upset, were reported by subjects in both groups. The authors report that 24-hour SBP (P = 0.045) and DBP (P = 0.039) and daytime SBP (P = 0.027) and DBP (P = 0.025) were significantly lower after OLE intake compared with the control. No significant between-group differences were observed in nighttime BP. Compared with the control intervention, OLE intake significantly reduced plasma TC (P = 0.002), LDL-C (P = 0.017), and triglyceride (P = 0.008) levels. Compared with baseline, the values of HDL-C significantly decreased following consumption of OLE (P < 0.05); however, no between-group differences in changes were seen for HDL-C or the LDL-C/HDL-C ratio. OLE significantly reduced the cytokine interleukin (IL)-8 compared with the control (P < 0.05). IL-8 is associated with an increased risk for future CVDs.1 No significant effects were seen after consumption of OLE or the control for other markers of glycemic control or inflammation or on body composition. Oleuropein is thought to be the OLE component responsible for its hypotensive effects. The mechanisms behind the lipid-lowering effects of OLE are unknown, but animal studies suggest that the consumption of OLE's phenolic compounds decreases the activities of cholesterol regulatory enzymes. Other studies suggest L-type Ca2+ channel antagonistic effects. Although no effects of OLE on glycemic control were observed, the authors cite a study in which olive leaf polyphenols improved insulin sensitivity in overweight, middle-aged men.2 The authors conclude, "Daily consumption of OLE can result in favourable improvements in several CVD risk factors which could result in a moderate but nonetheless significant reduction in risk, making it a useful addition to a healthy diet and lifestyle." Comvita Limited and Callaghan Innovation (Wellington, New Zealand) provided 50% of the funding for the study as a Technology for Business Growth grant. Comvita Limited, manufacturer of the OLE, did not participate in the design, execution, or analysis of the study. ―Shari Henson References 1Boekholdt SM, Peters RJG, Hack CE, et al. IL-8 plasma concentrations and the risk of future coronary artery disease in apparently healthy men and women: the EPIC-Norfolk prospective population study. Arterioscler Thromb Vasc Biol. 2004;24(8):1503-1508. 2de Bock M, Derraik JGB, Brennan CM, et al. Olive (Olea europaea L.) leaf polyphenols improve insulin sensitivity in middle-aged overweight men: a randomized, placebo-controlled, crossover trial. PLoS One. 2013;8(3):e57622. doi: 10.1371/journal.pone.0057622.