Effects of 5-Methyltetrahydrofolic Acid Supplementation on Maternal Health and One-Carbon Metabolism During Lactation (OCMS)

March 27, 2026 updated by: Fundació Sant Joan de Déu

This double-blind, randomized, placebo-controlled parallel trial evaluates the effects of maternal 5-methyltetrahydrofolate (5-MTHF) supplementation during breastfeeding. Thirty-six lactating mother-infant dyads will be randomized (1:1) to receive 5-MTHF or placebo for 6 weeks, stratified by infant sex and mode of delivery. Tolerability and adverse events will be monitored.

Pre- and post-intervention assessments include breast milk one-carbon metabolites and oligosaccharides; maternal plasma one-carbon metabolites and metabolic health markers. Maternal mental health will be evaluated using the SCL-90-R questionnaire. A follow-up visit at 4 months will reassess infant anthropometry and microbiome outcomes.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

36

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Marta Ramon Krauel, MD PhD
  • Phone Number: Ext. 71263 (+34) 93 280 40 00
  • Email: marta.ramon@sjd.es

Study Locations

  • Spain
    • Barcelona
      • Barcelona, Barcelona, Spain, 08950

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Maternal age between 18 and 42 years
  • Gestational age at birth ≥ 37 weeks.
  • Exclusive breastfeeding at enrollment.
  • Infant age 0-1 months

Exclusion Criteria:

  • Multiple pregnancy
  • Presence of disease or malformations in the infant.
  • Weight-Standard Deviation Score < -1 at enrollment.
  • Use of folate-containing multivitamin supplements during breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Other: Placebo
Matching placebo administered daily for 6 weeks during lactation.
Experimental: 5-MTHF Supplementation
Dietary Supplement (5-MTHF)
Dietary supplement: 5-MTHF Supplementation
Oral supplementation with 5-MTHF (800 µg) administered daily for 6 weeks during lactation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Adverse Events
Time Frame: Baseline, 6 weeks, 4 months
Treatment safety and tolerability will be evaluated by assessing differences in the incidence of potential adverse events between groups, focusing on gastrointestinal symptoms.
Baseline, 6 weeks, 4 months
Change in breast milk 5-MTHF concentration
Time Frame: Baseline, 6 weeks
Change in breast milk 5-MTHF concentration measured with liquid chromatography coupled to mass spectrometry (LC-MS) from Baseline to 6 weeks.
Baseline, 6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in plasma 5-MTHF concentration
Time Frame: Baseline, 6 weeks
Change in maternal plasma 5-MTHF concentration measured with liquid chromatography coupled to mass spectrometry (LC-MS) from Baseline to 6 weeks.
Baseline, 6 weeks
Change in breast milk one-carbon metabolite concentration
Time Frame: Baseline, 6 weeks
Change in breast milk one-carbon-related metabolites (choline, methionine, SAM, SAH, homocysteine, cystathionine, folic acid, betaine) from Baseline to 6 weeks.
Baseline, 6 weeks
Change in plasma one-carbon metabolite concentration
Time Frame: Baseline, 6 weeks
Change in plasma one-carbon-related metabolites (choline, methionine, SAM, SAH, homocysteine, cystathionine, folic acid, betaine) from Baseline to 6 weeks.
Baseline, 6 weeks
Change in Human Milk Oligosaccharide (HMO) concentration
Time Frame: Baseline, 6 weeks
Change in HMO concentrations between Baseline and 6 weeks
Baseline, 6 weeks
Change in Maternal Plasma Glucose Concentration
Time Frame: Baseline, 6 weeks
Change in maternal blood glucose levels between baseline and 6 weeks.
Baseline, 6 weeks
Change in Maternal Plasma Glycated Hemoglobin (HbA1c) Concentration
Time Frame: Baseline, 6 weeks
Change in maternal blood glycated hemoglobin (HbA1c) between baseline and 6 weeks.
Baseline, 6 weeks
Change in Maternal Plasma Insulin Concentration
Time Frame: Baseline, 6 weeks
Change in maternal blood insulin levels between Baseline and 6 weeks.
Baseline, 6 weeks
Change in Maternal Plasma Triglyceride (TAG) Concentration
Time Frame: Baseline, 6 weeks
Change in maternal blood triglyceride (TAG) levels between baseline and 6 weeks.
Baseline, 6 weeks
Change in Maternal Blood Total Cholesterol Concentration
Time Frame: Baseline, 6 weeks
Change in maternal blood total Cholesterol levels between baseline and 6 weeks.
Baseline, 6 weeks
Change in Maternal Blood LDL Cholesterol Concentration
Time Frame: Baseline, 6 weeks
Change in maternal low-density lipoprotein (LDL) cholesterol levels between baseline and 6 weeks.
Baseline, 6 weeks
Change in Maternal Blood HDL Cholesterol Concentration
Time Frame: Baseline, 6 weeks
Change in maternal high-density lipoprotein (HDL) cholesterol levels between baseline and 6 weeks.
Baseline, 6 weeks
Change in Maternal Blood Alanine Aminotransferase (ALT) Levels
Time Frame: Baseline, 6 weeks
Change in maternal alanine aminotransferase (ALT) levels between baseline and 6 weeks.
Baseline, 6 weeks
Change in Maternal Blood Aspartate Aminotransferase (AST) Levels
Time Frame: Baseline, 6 weeks
Change in maternal aspartate aminotransferase (AST) levels between baseline and 6 weeks.
Baseline, 6 weeks
Change in Maternal Blood Gamma-Glutamyl Transferase (GGT) Levels
Time Frame: Baseline, 6 weeks
Change in maternal gamma-glutamyl transferase (GGT) levels between baseline and 6 weeks.
Baseline, 6 weeks
Change in Symptom Checklist-90-Revised (SCL-90-R) scale
Time Frame: Baseline, 3 weeks
The SCL-90-R is a 90-item self-report questionnaire assessing psychological symptoms over the past week, with a range of 0-90 across 9 dimenions: Somatization, Obsessive-compulsive, Interpersonal sensitivity, Depression, Anxiety, Hostility, Phobic anxiety, Paranoid ideation, Psychoticism. Higher scores indicate worse outcome.
Baseline, 3 weeks
Change in infant BMI z-score
Time Frame: Baseline, 6 weeks
We will measure infant body weight, length, and head circumference to calculate BMI z-scores according to WHO growth standards, and changes between baseline, 6 weeks and 4 months will be assessed.
Baseline, 6 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maternal and infant gut microbiome composition
Time Frame: Baseline, 6 weeks
Bacterial DNA will be isolated from infant and maternal fecal samples and sequenced to obtain microbiome composition.
Baseline, 6 weeks
Maternal plasma and breast milk metabolomic profile
Time Frame: Baselina, 6 weeks
The metabolomic profile will be obtained with the Biocrates Quant 1000 kit from plasma and breast milk samples.
Baselina, 6 weeks
Milk imprinted protein levels
Time Frame: Baseline, 6 weeks
Imprinted proteins in human milk samples will be analyzed by ELISA.
Baseline, 6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundació Sant Joan de Déu

Investigators

  • Principal Investigator: Carles Lerin, PhD, Fundació Sant Joan de Déu

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 15, 2026

Primary Completion (Estimated)

November 30, 2026

Study Completion (Estimated)

February 28, 2027

Study Registration Dates

First Submitted

March 19, 2026

First Submitted That Met QC Criteria

March 27, 2026

First Posted (Actual)

April 2, 2026

Study Record Updates

Last Update Posted (Actual)

April 2, 2026

Last Update Submitted That Met QC Criteria

March 27, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PIC-143-25

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breastfeeding

Clinical Trials on 5-MTHF Supplementation

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Jordan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe