Polyphenol Intake, Mediterranean Diet Adherence, and Oxidative Stress in Pregnancy (PREGPOLY)

Effect of Polyphenol Intake and Adherence to the Mediterranean Diet on Oxidative Stress During Pregnancy

This study is a randomized controlled clinical trial designed to evaluate the effect of a polyphenol-rich dietary intervention during pregnancy on endothelial function, oxidative stress biomarkers, and maternal and neonatal outcomes.

Pregnancy is associated with metabolic and vascular adaptations, and complications such as gestational diabetes and hypertensive disorders are linked to endothelial dysfunction and increased oxidative stress. Dietary factors, particularly adherence to the Mediterranean diet and intake of polyphenol-rich foods, may play a protective role.

Pregnant women will be randomly assigned to either an intervention group or a control group. The intervention consists of daily consumption of 10 g of natural non-alkalized cocoa and structured dietary counseling aimed at achieving at least five daily servings of fruits and vegetables, alongside general Mediterranean diet recommendations.

The intervention will last 12 weeks, from early to mid-pregnancy. Biomarkers of endothelial function and oxidative stress will be measured at different time points, along with clinical maternal outcomes (including gestational diabetes and hypertensive disorders) and neonatal outcomes.

The aim is to determine whether this dietary intervention improves endothelial function, reduces oxidative stress, and contributes to better pregnancy outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Pregnancy; Hypertension, Pregnancy-Induced; Endothelial Dysfunction; Oxidative Stress; Preeclampsia; Gestational Diabetes Mellitus (GDM)
• Intervention / Treatment: Dietary supplement: Natural Non-Alkalized Cocoa; Behavioral: Polyphenol-Rich Dietary Counseling

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ana García Albarrán, RN, Midwife; Phone Number: 923291100; Email: annagarcialbarran@usal.es
• Study Contact Backup: Name: María Begoña Ayuda Durán, PharmD; Phone Number: +34 923 294 537; Email: bego_ayuda@usal.es

Study Locations

• Spain
  • SALAMANCA
    • Salamanca, SALAMANCA, Spain, 37007
      • Hospital de Salamanca
      • Contact: Ana García Albarrán, RN, Midwife; Phone Number: 923291100; Email: annagarcialbarran@usal.es

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pregnant women aged 18 years or older.
• Singleton pregnancy.
• Gestational age between 8 and 11 weeks at enrollment.
• Receiving prenatal care within the Salamanca Health Area.
• Able to understand the study information and provide written informed consent.
• No clinical restrictions that would contraindicate dietary modifications.

Exclusion Criteria:

• Medical or obstetric conditions that contraindicate dietary modifications.
• Active metabolic, renal, or hepatic disease.
• Severe hyperemesis gravidarum or gastrointestinal disorders limiting food intake.
• Allergy or intolerance to cocoa.
• Habitual high cocoa or chocolate consumption (>30 g/day).
• Multiple pregnancy.
• Severe obstetric complications diagnosed before enrollment.
• Inability to comply with study procedures, attend follow-up visits, or communication barriers that could interfere with participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; Participants will receive a daily dietary intervention consisting of 10 g of natural non-alkalized cocoa and structured nutritional counseling aimed at achieving at least five daily servings of fruits and vegetables, in addition to general Mediterranean diet recommendations. The intervention will last 12 weeks during pregnancy.	Dietary supplement: Natural Non-Alkalized Cocoa; Structured nutritional counseling aimed at achieving at least five daily servings of fruits and vegetables and improving adherence to the Mediterranean diet.; Behavioral: Polyphenol-Rich Dietary Counseling; Structured nutritional counseling aimed at achieving at least five daily servings of fruits and vegetables and improving adherence to the Mediterranean diet.
Active Comparator: Control Group; Participants will receive standard dietary advice based on general healthy eating and Mediterranean diet recommendations during pregnancy, without specific supplementation or structured dietary intervention.	Behavioral: Polyphenol-Rich Dietary Counseling; Structured nutritional counseling aimed at achieving at least five daily servings of fruits and vegetables and improving adherence to the Mediterranean diet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum sVCAM-1 concentration	Change in serum soluble vascular cell adhesion molecule-1 (sVCAM-1) levels from baseline to 24-28 weeks of gestation, measured in [ng/mL].	Baseline, 24-28 weeks, and 32-36 weeks of gestation
Change in serum sFlt-1/PlGF ratio	Change in the soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) ratio from baseline to 24-28 weeks and 32-36 weeks of gestation.	Baseline, 24-28 weeks of gestation, and 32-36 weeks of gestation.
Change in serum nitric oxide concentration	Change in serum nitric oxide (NO) concentration from baseline to 24-28 weeks and 32-36 weeks of gestation, measured in [pg/mL].	Baseline, 24-28 weeks, and 32-36 weeks of gestation.
Change in serum IL-6 concentration	Change in circulating interleukin-6 levels between baseline and follow-up assessments, measured in [pg/mL].	Baseline, 24-28 weeks, and 32-36 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mediterranean Diet Adherence Screener (MEDAS) score	Change in adherence to the Mediterranean diet measured using the Mediterranean Diet Adherence Screener (MEDAS). Scores range from 0 to 14, with higher scores indicating greater adherence to the Mediterranean diet.	Baseline, 24-28 weeks of gestation, and 32-36 weeks of gestation.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of gestational diabetes mellitus	Occurrence of gestational diabetes mellitus diagnosed according to standard clinical criteria and routine screening procedures during pregnancy.	24-28 weeks of gestation.
Incidence of gestational hypertension	Occurrence of gestational hypertension diagnosed according to standard clinical criteria during pregnancy.	From enrollment until delivery.
Incidence of preeclampsia	Occurrence of preeclampsia diagnosed according to standard clinical criteria during pregnancy.	From enrollment until delivery.
Gestational age at delivery	Gestational age at the time of delivery measured in completed weeks of gestation.	At delivery.
Neonatal birth weight	Neonatal birth weight measured in grams.	At delivery.
Apgar score at 1 minute	Neonatal condition assessed using the Apgar score at 1 minute after birth. Scores range from 0 to 10, with higher scores indicating better neonatal condition.	At delivery.
Apgar score at 5 minutes	Neonatal condition assessed using the Apgar score at 5 minutes after birth. Scores range from 0 to 10, with higher scores indicating better neonatal condition.	At delivery.
Apgar score at 10 minutes	Neonatal condition assessed using the Apgar score at 10 minutes after birth. Scores range from 0 to 10, with higher scores indicating better neonatal condition.	At delivery.
Neonatal intensive care unit admission	Proportion of newborns requiring admission to the neonatal intensive care unit (NICU).	At delivery

Collaborators and Investigators

• Sponsor: University of Salamanca
• Investigators: Principal Investigator: Ana García Albarrán, RN, Midwife, University of Salamanca; Study Director: Susana González Manzano, PharmD, University of Salamanca; Study Director: María Begoña Ayuda Durán, PharmD, University of Salamanca

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: June 9, 2026
• First Submitted That Met QC Criteria: June 14, 2026
• First Posted (Actual): June 18, 2026

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 14, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Oxidative stress; Randomized controlled trial; Endothelial function; Polyphenols; Mediterranean diet; Cocoa supplementation
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Pregnancy Complications; Glucose Metabolism Disorders; Diabetes Mellitus; Hypertension; Nutritional and Metabolic Diseases; Diabetes, Gestational; Pre-Eclampsia; Hypertension, Pregnancy-Induced
• Other Study ID Numbers: USAL-CT-2026-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

At present, there is no finalized plan for sharing individual participant data (IPD). Due to the sensitive nature of maternal and neonatal health data and the presence of biological and clinical information, data sharing will be considered in accordance with institutional ethics requirements, participant consent, and applicable data protection regulations.

Any potential future sharing of de-identified data will be determined after study completion and in line with publication and regulatory requirements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No