Polyphenol Intake, Mediterranean Diet Adherence, and Oxidative Stress in Pregnancy

NCT07656532 | Not Yet Recruiting

• 1 other identifier: USAL-CT-2026-001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pregnancy; Gestational Diabetes Mellitus (GDM); Preeclampsia; Hypertension, Pregnancy-Induced; Oxidative Stress; Endothelial Dysfunction

Keywords

Mediterranean diet; Polyphenols; Cocoa supplementation; Oxidative stress; Endothelial function; Randomized controlled trial

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (1)

• Change in Mediterranean Diet Adherence Screener (MEDAS) score

  Baseline, 24-28 weeks of gestation, and 32-36 weeks of gestation.

Other Outcomes (9)

• Incidence of gestational diabetes mellitus

  24-28 weeks of gestation.

• Incidence of gestational hypertension

  From enrollment until delivery.

• Incidence of preeclampsia

  From enrollment until delivery.

Study Arms (2)

Intervention Group

EXPERIMENTAL

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; Behavioral: Polyphenol-Rich Dietary Counseling

Control Group

ACTIVE COMPARATOR

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

Interventions

Natural Non-Alkalized Cocoa DIETARY_SUPPLEMENT

Structured nutritional counseling aimed at achieving at least five daily servings of fruits and vegetables and improving adherence to the Mediterranean diet.

Intervention Group

Polyphenol-Rich Dietary Counseling BEHAVIORAL

Structured nutritional counseling aimed at achieving at least five daily servings of fruits and vegetables and improving adherence to the Mediterranean diet.

Control Group; Intervention Group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Salamanca: lead

Study Sites (1)

Hospital de Salamanca

Salamanca, SALAMANCA, 37007, Spain

Location

MeSH Terms

Conditions

Diabetes, Gestational; Pre-Eclampsia; Hypertension, Pregnancy-Induced

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Ana García Albarrán, RN, Midwife

  University of Salamanca

  PRINCIPAL INVESTIGATOR

• Susana González Manzano, PharmD

  University of Salamanca

  STUDY DIRECTOR

• María Begoña Ayuda Durán, PharmD

  University of Salamanca

  STUDY DIRECTOR

Central Study Contacts

Ana García Albarrán, RN, Midwife

CONTACT

923291100; annagarcialbarran@usal.es

María Begoña Ayuda Durán, PharmD

CONTACT

+34 923 294 537; bego_ayuda@usal.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Biological samples will be analyzed by laboratory staff blinded to group allocation. Samples will be coded prior to analysis to ensure that outcome assessors are unaware of whether participants belong to the intervention or control group. This procedure is intended to minimize measurement bias in biochemical and oxidative stress biomarkers.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI-PhD-Nurse and Midwife

Model Details: Participants will be randomly assigned in a 1:1 ratio to either an intervention group receiving a polyphenol-rich dietary intervention or a control group receiving standard dietary advice. Both groups will be followed in parallel throughout pregnancy.

Study Record Dates

• First Submitted: June 9, 2026
• First Posted: June 18, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: June 18, 2026

Record last verified: 2026-06

Locations

ES (1)