Entry #: 14
Date: 23 September 2017
Section: Phenolic Compounds
Topic: Hydroxytyrosol in human volunteers
Type: Human volunteer trial

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Expert review of literature related to olives and olive oil

D. Elizabeth McCord, Nancy B. Ray and Tom C. Karagiannis


Antioxidant effects of a hydroxytyrosol-based pharmaceutical formulation on body composition, metabolic state, and gene expression: A randomized double-blinded, placebo-controlled crossover trial


Colica C et al

Citation / Year

(1) / 2017


Mediterranean diet, hydroxytyrosol, antioxidant, superoxide dismutase 1 (SOD1), gastroresistant capsules


Extra-virgin olive is a main component accounting for the beneficial effects of the Mediterranean diet (2) as highlighted by the classical Seven Countries study (3) and more recently the Predimed study (4). The Food and Drug administration has previously allowed a qualified health claim for the ability of olive oil (23 g /day) to reduce the risk of coronary heart disease. While these large-scale studies have indicated the beneficial effects of extra-virgin olive oil in various disease, much research is required to elucidate the cellular and molecular mechanisms accounting for the beneficial effects of the various bioactive components. In this study human volunteers (n = 28; 12 M and 16 F) were treated with either 15 mg / day (2 capsules of 7.5 mg of hydroxytyrosol [HT] per capsule) of HT (an abundant phenolic antioxidant in extra-virgin olive oil) or placebo daily for a three week period. This is a well-designed randomised, double-blinded, crossover study with interesting anthropometric, biochemical and molecular parameters being investigated.

Key points and implications

An important aspect of this trial is the placebo controlled nature of the crossover study. The authors produced gastroresistant tablets composed of hard enteric coated (Eudraguard®) gelatin capsules (Fenolia™) with 7.5 mg HT from an elaVida™ olive extract in an organic extra-virgin olive oil vehicle. Placebo controls were formulated in the same way without the elaVida™ extract. To ensure gastric transit and intestinal absorption tablets were administered two hours before lunch, and indeed, plasma concentration of HT was measured to be 2.83 μg / mL. Pharmacokinetics and bioavailability is an important aspect when considering dietary phenolics; the issue has been addressed in an elegant study previously (5) and numerous others, however requires much further clarification.

Overall, this study highlighted the potential beneficial effects of HT administration with positive changes in general anthropometric parameters (weight and body fat percentage). Further, oxidation biomarkers were changed with increases in plasma thiols and total antioxidant status and decreases in nitrite, nitrate and malondialdehyde (lipid peroxidation marker). Gene expression changes were also measured for a panel of key proteins in inflammatory and oxidative stress pathways. These included APOE, MIF, SOD1, PPARγ, ACE, MTHFR, CAT, CCL2 and NFKB1. The findings indicated that at the time-point measured, HT induced a significant (approximately 4-fold) increase in the expression of the SOD1 gene. As identified by the authors, the main limitation is the relatively small size of the study (n = 28) and perhaps the short duration of the intervention (3 weeks) represents another shortcoming. Nevertheless, this study adds considerable new knowledge to the field and the data do provide the basis future larger-scale clinical trials.

Related publications

  1. C. Colica et al., Antioxidant Effects of a Hydroxytyrosol-Based Pharmaceutical Formulation on Body Composition, Metabolic State, and Gene Expression: A Randomized Double-Blinded, Placebo-Controlled Crossover Trial. Oxidative medicine and cellular longevity 2017, 2473495 (2017).
  2. W. C. Willett, The Mediterranean diet: science and practice. Public health nutrition 9, 105-110 (2006).
  3. F. Fidanza, A. Alberti, M. Lanti, A. Menotti, Mediterranean Adequacy Index: correlation with 25-year mortality from coronary heart disease in the Seven Countries Study. Nutrition, metabolism, and cardiovascular diseases : NMCD 14, 254-258 (2004).
  4. R. Estruch et al., Primary prevention of cardiovascular disease with a Mediterranean diet. The New England journal of medicine 368, 1279-1290 (2013).
  5. M. N. Vissers, P. L. Zock, A. J. Roodenburg, R. Leenen, M. B. Katan, Olive oil phenols are absorbed in humans. The Journal of nutrition 132, 409-417 (2002).