Tuesday, 21 March 2017

Re: Acute Dose of Olive Leaf Extract Improves Vascular Function and Reduces Production of the Inflammatory Cytokine Interleukin-8 (IL-8)

  • Olive (Olea europaea, Oleaceae) Leaf
  • Vascular Function
  • Inflammatory Cytokines
Date: 03-15-2017HC# 081635-564

Lockyer S, Corona G, Yaqoob P, Spencer JP, Rowland I. Secoiridoids delivered as olive leaf extract induce acute improvements in human vascular function and reduction of an inflammatory cytokine: a randomised, double-blind, placebo-controlled, cross-over trial. Br J Nutr. 2015;114(1):75-83.

Partly because of its olive (Olea europaea, Oleaceae) fruit oil component, the Mediterranean diet is associated with a decreased risk for cardiovascular disease. The cardioprotective effects of olive oil are attributed to its phenolic constituents. Olive leaves contain significantly higher concentrations of phenolics than the olive fruit and its oil, and experimental studies have found that these phenols have antihypertensive, anti-inflammatory, antioxidant, and vasoactive effects. These authors conducted a randomized, double-blind, placebo-controlled, crossover trial to investigate the postprandial effects of olive leaf extract (OLE) on 2 measures of cardiovascular risk, vascular function and inflammatory status.
In May 2011, the authors recruited healthy males and females from the University of Reading and the surrounding area in Berkshire, United Kingdom, through email and poster advertisements. Included subjects had not taken antibiotics during the previous 3 months and were not taking any lipid-modifying or blood-clotting medications or vitamin, mineral, and/or fish oil supplements. The exclusion criteria were as follows: smokers; alcohol consumption >21 units/week; any dietary restrictions; significant illness in the previous 12 months; gastrointestinal, blood-clotting, or metabolic disorders; pregnancy or breastfeeding; blood pressure ˃150/90 mmHg; hemoglobin <125 g/l for men and <110 g/l for women; gamma-glutamyl transferase ˃1.3 µkat/l; and cholesterol ˃6.5 mmol/l.
Twenty eligible subjects were included in the crossover trial, which was comprised of 2 study visits ~4 weeks apart. Two subjects were lost to follow-up after the first study visit. The 18 remaining subjects (9 males and 9 females; aged 19-40 years) attended 2 study visits at the Hugh Sinclair Nutrition Unit at the University of Reading between June 2011 and September 2011. The subjects were asked to follow a low-polyphenol diet for 24 hours before each study day and compliance was confirmed by analysis of baseline urine samples using high-performance liquid chromatography (HPLC).
On each study day, a baseline fasting blood sample and urine sample were collected. The subjects then ingested either 4 capsules containing OLE or 4 placebo control capsules. Each OLE capsule contained 400 mg OLE in 672.5 mg safflower (Carthamus tinctorius, Asteraceae) seed oil; the 4 capsules delivered a total of 51.12 mg oleuropein and 9.67 mg hydroxytyrosol (HT). Each placebo capsule contained 900 mg of safflower oil. All capsules were provided by Comvita New Zealand Limited (Te Puke, New Zealand).
Blood samples were collected at 1, 3, and 6 hours after capsule ingestion, and urine was collected at 0-4, 4-8, and 8-24 hours. The total volume of urine produced during each time period was recorded. Arterial stiffness using the digital volume pulse stiffness index (DVP-SI) was used as a measure of vascular function. DVP-SI was assessed at 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after capsule ingestion.
After the 4-hour sample collections, the subjects ate a standard low-fat lunch of low-phenolic content, and after the 8-hour collections, they ate a low-phenolic meal. The bioavailability of OLE phenolic constituents was assessed using HPLC analysis of the urine samples to determine the concentration of oleuropein, HT, tyrosol, homovanillic alcohol (HValc), 3,4-dihydroxyphenylethanol-elenolic acid (EA, oleuropein aglycone), and 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde (EDA, oleuropein aglycone di-aldehyde) in the urine. For each blood sample, the supernatant derived from whole blood culture was analyzed to determine the concentration of the inflammatory cytokines interleukin (IL)-6, IL-1β, IL-10, IL-8, and tumor necrosis factor-α.
DVP-SI decreased significantly after consumption of the OLE capsules compared with the placebo capsules (P=0.0085). Ex vivo IL-8 production was significantly lower after OLE consumption than after the control capsules (P=0.0326). There was no significant treatment effect on the production of the other cytokines. "[T]he reduction in ex vivo production of IL-8 by an acute dose of OLE may at least partly explain the post-ingestion reduction in DVP-SI," write the authors. HT, tyrosol, HValc, EDA, oleuropein, and EA were found in the urine samples after the intake of OLE. The level of HT and its conjugates in the urine peaked at 4-8 hours. The concentration of HValc and its conjugates peaked at 8-24 hours. Compounds derived from oleuropein and eluting between 30 and 60 min (including EA and EDA) were grouped together and quantified as oleuropein equivalents; oleuropein equivalents peaked at 8-24 hours after OLE consumption.
"[W]e provide evidence that acute consumption of OLE, an alternative source of olive phenolics, improves vascular function and reduces the production of an inflammatory cytokine," conclude the authors. They acknowledge that the product used has not been completely characterized and that other bioactives previously identified in OLE, such as minerals, triterpenoids, and squalene,1 could be responsible for the observed response. It should be noted that OLE consumption increased DVP-SI, although there was a trend in the data (P=0.074) suggesting that OLE may attenuate postprandial arterial stiffness. An advantage of the OLE intervention is that it provides significant levels of olive phenolics without the high fat content of olive oil. A longer-duration trial involving a larger sample size is warranted to further explore potential benefits of OLE.
This study was funded by Comvita Limited and Callaghan Innovation (Lower Hutt, New Zealand), who supported 50% of the funding as a Technology for Business Growth grant. "Comvita had no part in the design or running of the study or analysis; therefore, the authors declare no conflict of interest."
Shari Henson
1Preedy VR, Watson RR, eds. Olives and Olive Oil in Health and Disease Prevention. London, UK: Elsevier Inc.; 2010.