Entry #: 6
Date: 4 July 2017
Section: Phenolic compounds
Topic: Hydroxytyrosol in human volunteers
Type: Human volunteer trial

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

Hydroxytyrosol supplementation increases vitamin C levels in vivo. A human volunteer trial.


Lopez-Huertas E and Fonolla J

Citation / Year

(1) / 2017


Hydroxytyrosol, olive phenolics, olive mill waste, vitamin C, human volunteer trial


This a small repeated measures trial (no randomization or placebo control) study measuring the effects of administration of purified hydroxytyrosol (99.5%, 45 mg for eight weeks) in 14 volunteers with borderline high total cholesterol (200-239 mg/dL), and no other cardiovascular risk factors. Following dietary instructions, which included refraining from consuming olives, olive oil, or olive-derived products for 14 days, and baseline measurement (at T0), volunteers were given the hydroxytyrosol supplement (single oral dose, 45 mg in 40 mL sterile saline) daily between 10 am – 12 pm for eight weeks. Hydroxytyrosol was purified from olive mill waste water using chromatography using previously published methodologies (2). Calculations from the authors indicate that the dose of hydroxytyrosol administered in this study is equivalent to approximately 30 g olive fruit (10-15 olives from a phenol rich variety) (3). Essentially, this was an extension of a previous in vivo – rabbit model of diet-induced atherosclerosis – in which the authors supplemented the animals with 4 mg/Kg pure hydroxytyrosol (4). They had shown that hydroxytyrosol improves blood lipid profiles, antioxidant status and reductions in the size of atherosceloritic lesions (4). The aim of this study was to examine the effect of chronic administration (8 weeks) of hydroxytyrosol on various parameters including cardiovascular risk, blood lipids, antioxidant parameters, enzyme functions and vitamins and minerals in volunteers (14) with mild hyperlipidemia.

Key points and implications

Being a repeated measures study, the authors measured the various parameters of interest at four (T4, half-way through the trial) and eight weeks (T8, completion of trial) following supplementation with hydroxytyrosol. Values for each volunteer at T4 and T8 were compared to analogous baseline values. The findings indicated that daily supplementation with 45 mg hydroxytyrosol was tolerated over the week period, and (self-reported) compliance was adequate, with all 14 volunteers completing the eight week study. The results for most of cardiovascular risk factor, blood lipid and biochemical parameters were unremarkable with negligible changes over the eight week period. However, a decrease in serum ferritin and trend towards increasing level of transferrin were observed. Similarly, a significant decrease in mean corpuscular hemoglobin concentration was observed at T4. These findings indicate that hydroxytyrosol may regulate iron stores, are in line with the iron-chelation (transient) properties of hydroxytyrosol (5), and require further investigation in the context of iron deficiency and anemia. Hydroxytyrosol was shown to reduce serum folate levels and the mechanism responsible (e.g. inhibition of intestinal folate uptake, or modulation of dihydrofolate reductase) requires further clarification. Apart from being well-tolerated, the major positive finding from this trial was the increase in serum vitamin C (two-fold at T4 and sustained at T8) levels following supplementation with hydroxytyrosol. Overall, increasing endogenous levels of vitamin C, highlights an additional (indirect) mechanism for the antioxidant effects of hydroxytyrosol.

Related publications

  1. E. Lopez-Huertas, J. Fonolla, Hydroxytyrosol supplementation increases vitamin C levels in vivo. A human volunteer trial. Redox Biol 11, 384-389 (2017).
  2. M. Gonzalez-Santiago, J. Fonolla, E. Lopez-Huertas, Human absorption of a supplement containing purified hydroxytyrosol, a natural antioxidant from olive oil, and evidence for its transient association with low-density lipoproteins. Pharmacol Res 61, 364-370 (2010).
  3. C. Romero et al., Effect of cultivar and processing method on the contents of polyphenols in table olives. J Agric Food Chem 52, 479-484 (2004).
  4. M. Gonzalez-Santiago et al., One-month administration of hydroxytyrosol, a phenolic antioxidant present in olive oil, to hyperlipemic rabbits improves blood lipid profile, antioxidant status and reduces atherosclerosis development. Atherosclerosis 188, 35-42 (2006).
  5. N. Kitsati, M. D. Mantzaris, D. Galaris, Hydroxytyrosol inhibits hydrogen peroxide-induced apoptotic signaling via labile iron chelation. Redox Biol 10, 233-242 (2016).

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