Hydroxytyrosol, a Promising Supplement in the Management of Human Stroke: An Exploratory Study

Abstract

Hydroxytyrosol (HT) is a bioactive olive oil phenol with beneficial effects in a number of pathological situations. We have previously demonstrated that an HT-enriched diet could serve as a beneficial therapeutic approach to attenuate ischemic-stroke-associated damage in mice. Our exploratory pilot study examined this effect in humans. Particularly, a nutritional supplement containing 15 mg of HT/day was administered to patients 24 h after the onset of stroke, for 45 days. Biochemical and oxidative-stress-related parameters, blood pressure levels, serum proteome, and neurological and functional outcomes were evaluated at 45 and 90 days and compared to a control group. The main findings were that the daily administration of HT after stroke could: (i) favor the decrease in the percentage of glycated hemoglobin and diastolic blood pressure, (ii) control the increase in nitric oxide and exert a plausible protective effect in oxidative stress, (iii) modulate the evolution of the serum proteome and, particularly, the expression of apolipoproteins, and (iv) be beneficial for certain neurological and functional outcomes. Although a larger trial is necessary, this study suggests that HT could be a beneficial nutritional complement in the management of human stroke.

Keywords: HbA₁c; blood pressure; hydroxytyrosol; ischemic stroke; lipid profile; neurological and functional outcomes; oxidative-stress-related markers; proteomics.

Figure 1

(a,b) Boxplots presenting median and quartiles of TC and LDL-C values, respectively, and (c) profile plot of HbA₁c in control and HT-treated stroke patients at 0, 45, and 90 days. * p-value = 0.034.

Figure 2

Oxidative-stress-related parameters at 0, 45, and 90 days after stroke in control and HT-treated patients. (a,c) Boxplots showing median and quartiles and (b,d) profile plots of the distribution of NO and TBARS levels. * p-value = 0.034.

Figure 3

Blood pressure profile plots of patients 0, 45, and 90 days after stroke in control and HT-treated patients. (a) SBP and (b) DBP.

Figure 4

Canonical pathways modified in (a) HT and (b) control groups at 45 versus 0 days. Bars in orange (upregulated) and blue (downregulated) indicate z-score values greater or lower than 2. Pathways with a −log (p-value) over 1.3 are shown.

Figure 5

Canonical pathways modified in (a) HT and (b) control groups at 90 versus 0 days. Bars in orange (upregulated) and blue (downregulated) indicate z-score values greater or lower than 2. Top 15 pathways with a −log (p-value) over 1.3 are shown.

Figure 6

Boxplots showing median and quartiles of the HGS of (a) paretic limbs and (b) non-paretic limbs in patients 0, 45, and 90 days after stroke. * p-value = 0.034.