Hydroxytyrosol Dietary Supplement and Prevention of Age-Related Diseases (HT15)

Health Effects of Chronic Supplementation with a Natural Extract High in Hydroxytyrosol in Individuals At High Risk of Developing Age-related Diseases

The primary objective of this study is to ascertain the effects of chronic consumption of a hydroxytyrosol-rich extract from olive in a population at high risk of developing age-related pathologies such as type 2 diabetes and cardiovascular diseases. The markers measured will be associated with oxidative stress, inflammation, and homeostasis glucose and lipid profiles. Improvements in these parameters could potentially prevent the onset of pathologies associated with aging.

Study Overview

• Status: Completed
• Conditions: Overweight; PreDiabetes
• Intervention / Treatment: Dietary supplement: Group 2, capsule of placebo; Dietary supplement: Group 1, hydroxytyrosol-rich extract capsule

Detailed Description

Fifty subjects 40-75 years old overweight (BMI between 24-29,9 kg/m2) and prediabetes (fasting blood sugar between 100-126 mg/dl and/or glycated hemoglobin between 5,7-6,4%) will be recruited. Detailed inclusion and exclusion criteria are provided below.

Participants will be randomly divided into two groups, one to consume the Hytolive® capsule and the other a placebo. The intervention study has been designed for daily consumption before breakfast of one capsule for 16 weeks. The study includes a two-week washout period during which subjects will not be allowed to consume olives or virgin olive oil.

At the beginning and end of the study, upon arrival at the ICTAN-CSIC Human Nutrition Unit, volunteers will provide a urine sample corresponding to the first morning void, and a nurse will draw a fasting blood sample (20 mL distributed in tubes with various anticoagulants for measurements). Additionally, their blood pressure will be measured, and a complete anthropometric and body composition study will be conducted. Furthermore, volunteers will provide a stool sample from the preceding days (these samples will not be used in this study but will be stored at -80°C for potential future determination of the intestinal microbiota metagenomic profile). Subsequently, dietary controls will be conducted, physical activity and emotional well-being tests will be administered, and fatigue will be evaluated. Additionally, there will be an interim visit aimed at verifying adherence to supplementation. For this purpose, volunteers will provide a urine sample corresponding to the first morning void on an empty stomach, in which levels of hydroxytyrosol and its derivatives will be determined. Likewise, dietary and physical activity controls will be conducted to confirm that volunteers are not altering their habits.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Comunidad Autónoma de Madrid
    • Madrid, Comunidad Autónoma de Madrid, Spain, 28040
      • Institute of Food Science, Technology and Nutrition, National Research Council (ICTAN-CSIC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Prediabetes (defined as fasting glucose levels according to the American Diabetes Association guideline, with fasting blood glucose ≥100 and <126 mg/dL, or hemoglobin A1c levels ranging from 5.7% to 6.4%)
• Overweight (body mass index BMI 24-29.9 kg/m2)

Exclusion Criteria:

• Any prior diagnosis of diabetes, hypertension, hyperlipidemia, other cardiovascular diseases, thyroid gland disorders, asthma, arthritis, or inflammatory conditions, cirrhosis, or other liver diseases
• Weight loss > 2.5 kg in the last 6 months
• Being on pharmacological treatment of any kind
• Taking dietary supplements containing antioxidants other than vitamins
• Being a smoker or habitual alcohol consumer; being HIV positive
• Being pregnant or breastfeeding
• Blood pressure ≥ 140 mmHg (systolic) and ≥ 90 mmHg (diastolic)
• Total cholesterol ≥ 240 mg/dL, LDL cholesterol ≥ 160 mg/dL, or TG ≥ 200 mg/dl

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Capsule of placebo. Group 2; Intake of one capsule placebo/day without hydroxytyrosol before breakfast for 16 weeks.	Dietary supplement: Group 2, capsule of placebo; Following a two-week washout period, the subjects will receive a bottle containing capsules (Placebo) (Group 2). Blood, urine, and fecal samples will be collected from each participant during their stay at the Human Nutrition Unit at the beginning and end of the study. Subjects will be instructed to refrain from consuming products rich in hydroxytyrosol (such as virgin olive oil and olives) and to maintain their usual dietary habits throughout the study. Additionally, olive oil (1L/week) will be provided to each volunteer that will consume during intervention study as the sole source of dietary fat, used for cooking, salad dressing, toasts, etc. in order to control the extra consumption of hydroxytyrosol.
Experimental: Capsule of an olive extract with a high content of hydroxytytorosol. Group 1; Intake of one capsule/day containing 15 mg of hydroxytyrosol before breakfast for 16 weeks.	Dietary supplement: Group 1, hydroxytyrosol-rich extract capsule; Following a two-week washout period, the subjects will receive a bottle containing capsules (Group 1). Blood, urine, and fecal samples will be collected from each participant during their stay at the Human Nutrition Unit at the beginning and end of the study. Subjects will be instructed to refrain from consuming products rich in hydroxytyrosol (such as virgin olive oil and olives) and to maintain their usual dietary habits throughout the study. Additionally, olive oil (1L/week) will be provided to each volunteer that will consume during intervention study as the sole source of dietary fat, used for cooking, salad dressing, toasts, etc. in order to control the extra consumption of hydroxytyrosol apart from that provided by the capsule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDL-ox as marker of oxidative status	Differences between subjects supplemented with hydroxytyrosol and non-supplemented subjects	Up to six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mental well-being determined by Warwick-Edinburgh Mental Well-being Scale	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to two months
Sleep quality determined by Pittsburgh Sleep Quality Index	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to two months
Fatigue test determined by Borg Rating Of Perceived Exertion	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to two months
Fasting glucose	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
Fasting insulin	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
Glycated hemoglobin (HbA1c)	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
Glucagon-like peptide-1 (GLP-1)	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
Total cholesterol	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
High density lipoproteins (HDL)	Differences between subjects supplemented with hydrpxytyrosol and no-supplemented subjects	Up to six months
Low density lipoproteins (LDL)	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
Triglycerides	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
Apoliporpotein A1	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
Apoliporpotein B	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
Total antioxidant status (TAS)	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
Total oxidative status (TOS)	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
Oxides of nitrogen (NOx)	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
Thiobarbituric acid reactive substances (TBARS)	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
C reactive protein	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
Interleukine 6 (IL-6)	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
Tumor necrosis factor alpha (TNF-α)	Differences between subjects supplemented with hydroxytyrosoland no-supplemented subjects	Up to six months
Alanine aminotransfesare (transaminases ALT)	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months
Aspartate aminotransferase (transaminase AST)	Differences between subjects supplemented with hydroxytyrosol and no-supplemented subjects	Up to six months

Collaborators and Investigators

• Sponsor: National Research Council, Spain
• Collaborators: Genosa I+D
• Investigators: Principal Investigator: Raquel Mateos, PhD, Institute of Food Science, Technology and Nutrition (ICTAN-CSIC)

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Actual): September 30, 2024
• Study Completion (Actual): December 20, 2024

Study Registration Dates

• First Submitted: February 20, 2024
• First Submitted That Met QC Criteria: February 28, 2024
• First Posted (Actual): March 6, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 10, 2025
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Prediabetes; Hydroxytyrosol; Antioxidant; Age-related diseases
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperglycemia; Overweight; Prediabetic State; Glucose Intolerance; Anti-Infective Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Antioxidants; Protective Agents; 3,4-dihydroxyphenylethanol
• Other Study ID Numbers: HT15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No