Breastfeeding
Conditions
Keywords
5-Methyltetrahydrofolate (5-MTHF), One-carbon metabolism, Human milk oligosaccharides, Breast milk composition, Betaine, Early-life nutrition, Maternal supplementation, Maternal mental health, 5-MTHF, Gut Microbiome, Metabolomics, Infant Microbiota
Brief summary
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.
Interventions
DIETARY_SUPPLEMENT5-MTHF Supplementation
Oral supplementation with 5-MTHF (800 µg) administered daily for 6 weeks during lactation.
OTHERPlacebo
Matching placebo administered daily for 6 weeks during lactation.
Sponsors
Fundació Sant Joan de Déu
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 42 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | 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. |
| Change in breast milk 5-MTHF concentration | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in plasma 5-MTHF concentration | 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. |
| Change in breast milk one-carbon metabolite concentration | 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. |
| Change in plasma one-carbon metabolite concentration | Baseline, 6 weeks | Change in plasma one-carbon-related metabolites (choline, methionine, SAM, SAH, homocysteine, cystathionine, folic acid, betaine) from Baseline to 6 weeks. |
| Change in Human Milk Oligosaccharide (HMO) concentration | Baseline, 6 weeks | Change in HMO concentrations between Baseline and 6 weeks |
| Change in Maternal Plasma Glucose Concentration | Baseline, 6 weeks | Change in maternal blood glucose levels between baseline and 6 weeks. |
| Change in Maternal Plasma Glycated Hemoglobin (HbA1c) Concentration | Baseline, 6 weeks | Change in maternal blood glycated hemoglobin (HbA1c) between baseline and 6 weeks. |
| Change in Maternal Plasma Insulin Concentration | Baseline, 6 weeks | Change in maternal blood insulin levels between Baseline and 6 weeks. |
| Change in Maternal Plasma Triglyceride (TAG) Concentration | Baseline, 6 weeks | Change in maternal blood triglyceride (TAG) levels between baseline and 6 weeks. |
| Change in Maternal Blood Total Cholesterol Concentration | Baseline, 6 weeks | Change in maternal blood total Cholesterol levels between baseline and 6 weeks. |
| Change in Maternal Blood LDL Cholesterol Concentration | Baseline, 6 weeks | Change in maternal low-density lipoprotein (LDL) cholesterol levels between baseline and 6 weeks. |
| Change in Maternal Blood HDL Cholesterol Concentration | Baseline, 6 weeks | Change in maternal high-density lipoprotein (HDL) cholesterol levels between baseline and 6 weeks. |
| Change in Maternal Blood Alanine Aminotransferase (ALT) Levels | Baseline, 6 weeks | Change in maternal alanine aminotransferase (ALT) levels between baseline and 6 weeks. |
| Change in Maternal Blood Aspartate Aminotransferase (AST) Levels | Baseline, 6 weeks | Change in maternal aspartate aminotransferase (AST) levels between baseline and 6 weeks. |
| Change in Maternal Blood Gamma-Glutamyl Transferase (GGT) Levels | Baseline, 6 weeks | Change in maternal gamma-glutamyl transferase (GGT) levels between baseline and 6 weeks. |
| Change in Symptom Checklist-90-Revised (SCL-90-R) scale | 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. |
| Change in infant BMI z-score | 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. |
Countries
Spain
Contacts
CONTACTCarles Lerin, PhD
CONTACTMarta Ramon Krauel, MD PhD
PRINCIPAL_INVESTIGATORCarles Lerin, PhD
Fundació Sant Joan de Déu
Outcome results
None listed