Maternal Betaine Supplementation During Breastfeeding (BetMilk)

Developing more efficient and cost-effective prevention strategies to slow down the worldwide epidemic of obesity and chronic metabolic disease has become a public health imperative. Our previous results in humans demonstrate that lower breast milk betaine levels were associated with faster infant postnatal growth, a strong and potentially modifiable risk factor of future obesity. Betaine is a trimethylated derivative of glycine, which is present in multiple foods and occurs naturally in breast milk. In this study, we will perform a double-blind randomized placebo-controlled pilot clinical study, in which maternal diet will be supplemented with betaine for 3 months during breastfeeding; infant's growth and adiposity will be monitored until 12 months of age, and breast milk composition and gut microbiota analyzed. An additional follow-up visit will be conducted at 48 months of age to repeat microbiome analysis, determine adiposity, and perform cognitive development assessment.

Study Overview

• Status: Active, not recruiting
• Conditions: Overweight and Obesity
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Betaine

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Barcelona, Barcelona, Spain, 08950
      • Hospital Sant Joan de Déu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Maternal Pre-pregnancy BMI between 25 and 40.
• Willing to exclusively breastfeed for ≥ 3 months
• Infant gestational age at birth > 37 weeks
• Infant birth weight > -1 standard deviations
• Absence of infant disease or malformations at birth

Exclusion Criteria:

• Multiple pregnancy
• Lactose intolerance
• CBS deficiency (inherited disease)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 400 mg of lactose daily for 12 weeks	Dietary supplement: Placebo; The intervention with supplement will start during the first 48h after birth and will last for 12 weeks
Experimental: Supplement; 400 mg of betaine daily for 12 weeks	Dietary supplement: Betaine; The intervention with supplement will start during the first 48h after birth and will last for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from birth weight-for-length z score at 1 month	Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores.	Birth and 1 month
Change from birth weight-for-length z score at 3 months	Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores.	Birth and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from birth weight-for-length z score at 6 months	Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores.	Birth and 6 months
Change from birth weight-for-length z score at 12 months	Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores.	Birth and 12 months
Breast milk concentration of betaine and related metabolites	We will quantify betaine and related metabolites in maternal breast milk samples	1 and 3 months
Maternal circulating concentration of betaine and related metabolites	We will quantify betaine and related metabolites in maternal plasma samples	1 and 3 months
Infant urine concentration of betaine and related metabolites	We will quantify betaine and related metabolites in infant urine samples	1, 3, and 6, and 12 months
Maternal gut microbiome composition	DNA from maternal fecal samples will be sequenced to quantify abundance of the different bacterial groups.	1 and 3 months
Change from birth weight-for-length z score at 48 months	Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores.	Birth and 48 months
Infant Body composition	Total body and abdominal fat mass measured by DXA scan	3, 12 and 48 months
Infant gut microbiome composition	DNA from infant fecal samples will be sequenced to quantify abundance of the different bacterial groups.	1, 3, 6, 12 and 48 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breast milk microbiota composition	DNA from breast milk samples will be sequenced to quantify abundance of the different bacterial groups.	1 and 3 months
Breast milk metabolome	Liquid chromatography coupled to mass spectrometry will be used to obtain a comprehensive metabolic profile of breast milk samples	1 and 3 months
Child development (ASQ-3 questionnaire)	Developmental progress will be evaluated with the parental reported ASQ-3 questionnaires	1, 3, 6, and 12 months
Child development: Vineland Adaptive Behavior Scales-Third Edition (Vineland-3)- Parent/Caregiver	Respondents: Parents/caregivers This evaluation is used to assist in the diagnosis of intellectual and developmental disabilities and measure the adaptive behaviors of individuals. 9 subdomains 3 domains and a overall ABCa. Motor Skills (77). Maladaptive Behavior (44) items. Total 502 items. The main domains are: Communication, Daily Living Skills, Socialization, Motor Skills, and Maladaptive Behavior (optional). The domain scores yield an adaptive behavior composite. A scaled score typically tells us how well a child did on a specific sub-test, and a standard score typically tells us how well a child did on a broad domain (which is often made of sub-tests). Scaled Scores have a score range of 0 - 19 points, with an average score of 10 points.	48 months
Child development: Behavior Rating Inventory of Executive Function, Preschool Version (BRIEF-P)	Respondents: Parents/teachers. Information about a child's behaviour that is directly relevant to an understanding of that child's executive functioning. 63 items that measure various aspects of executive functioning: Inhibit, Shift, Emotional Control, Working Memory, and Plan/Organize. A Likert-type scale with "never," "sometimes," and "often" options for rating behavior. The raw scores for the clinical scales and composite indexes are converted into standardized T-scores. Higher scores on BRIEF-P clinical scales and composite indexes indicate greater difficulties with executive functions, while lower scores suggest fewer problems. Interpretation should consider clinical norms and the overall profile to assess the significance of the child's performance.	48 months
Child development: The Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition (WPPSI-IV)	Respondents: childs, in direct interaction with the examiner. Is an individually administered, standardized assessment designed to evaluate the intelligence of young children. The age range of the WPPSI-IV is divided into two age bands, ages 2:6-3:11 and ages 4:0-7:7. WPPSI-IV (ages 2:6-3:11) can be interpreted at three levels: FSIQ (Full Scale Quotient), Primary Indexes (VCI=Verbal Comprehension Index, VSI=Visual Spatial Index, WMI=Working Memory Index), and Ancillary Indexes (VAI=Verbal Acquisition Index, NVI=Nonverbal Index, GAI=General Ability Index). WPPSI-IV scores can be calculated manually or via software. Subtest raw scores convert to scaled scores (M=10, SD=3), which sum into composite scores (M=100, SD=15, e.g., FSIQ). Age-based percentiles are available. Practitioners can analyze discrepancies between composites and identify cognitive strengths and weaknesses. Higher scaled or composite scores indicate better performance on that subtest or domain.	48 months
Child development: Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI)	Respondents: Childs. Age range: 2:0-99:11. Copying geometric figures of increasing complexity to assess visual-motor integration. Helps assess the extent to which individuals can integrate their visual and motor abilities. Poor performance on the Beery VMI is associated with difficulties in spatial organization of written text and maths. Some studies propose a cut-off below the 25th percentile to identify below-average motor performance. This treshold is higher than the 15th and 16th percentile cut-offs used in research to indicate severe difficulties with motor coordination affecting daily life. Raw scores on the Beery VMI can range from 1 to 27, with a higher score reflecting a better performance. Raw scores can be converted into norm scores, which are adjusted for age.	48 months

Collaborators and Investigators

• Sponsor: Fundació Sant Joan de Déu

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2021
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (Actual): November 18, 2020

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Organic Chemicals; Amines; Quaternary Ammonium Compounds; Onium Compounds; Trimethyl Ammonium Compounds; Betaine
• Other Study ID Numbers: PIC-206-19

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