Lysine Requirements During Lactation

Determining Dietary Lysine Requirements in Healthy Lactating Women Using the Indicator Amino Acid Oxidation Technique

The study aims to establish lysine requirements using the indicator amino acid oxidation (IAAO) method in women exclusively breastfeeding a single infant aged 3-4 months, and how maternal lysine needs change once infant transition to complimentary feeding at a later age of 9-10 months. Each 8-hour study day will have an assigned test lysine intake ranging from deficient to excess. The diets will be provided in a complete protein shake format, meeting all nutrient requirements except for the test lysine intake. Breath samples evaluate the indicator's oxidation to determine protein synthesis in response to lysine intake. Urine and one blood sample will be collected to assess metabolite concentrations.

Study Overview

• Status: Completed
• Conditions: Lactation; Breastfeeding; Breastfeeding, Exclusive
• Intervention / Treatment: Other: Dietary Lysine Intakes

Detailed Description

This study is a single-day intervention study where participants will be studied in a repeated measures design, with an individual having the option of participating in up 4 test lysine intakes for each lactation stage. A minimum of 10 women will be recruited, and the investigators hope to retain the same women for 8 study days to minimize data variability.

Potential participants will meet the researchers for a 1-hour preliminary assessment, where the investigators will evaluate their eligibility to participate in the study. During each study day, the participants will randomly receive a lysine test intake ranging from deficient to excess. The study day diets will consist of 8 hourly isocaloric and isonitrogenous meals in a protein shake, each presenting 1/12 of the daily energy requirement. The diets are composed of crystalline amino acid mixtures based on the composition of egg protein.

A Carbon-13 (13C) stable isotope tracer ( L-[1-13C]phenylalanine) will be added to the 5th-8th meal. The investigators will measure the rate of oxidation of this tracer expired in breath and the flux of this tracer by its enrichment in urine. The investigators will also collect a single blood sample to measure lysine metabolites. Lysine requirements will be determined by a two-phase linear regression crossover model on L-[1-13C]phenylalanine tracer oxidation using mixed-models regression to take repeated measures into account. The oxidation rate of the indicator amino acid exhibits a linear increase as the lysine intake rises until it reaches a plateau. The point at which this steady state is reached signifies that the test amino acid is predominantly utilized for protein synthesis. The primary endpoint is the lysine intake level at which the transition occurs from indicator oxidation (linear increase) to protein synthesis (plateau).

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4H4
      • BC Children's Hospital Research Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy
• Female
• 20-40 years
• Had a singleton pregnancy and is breastfeeding a single child.
• Exclusively breastfeeding an infant 3 - 4 months of age OR complimentary. feeding an infant 9-10 months of age.

Exclusion Criteria:

• Participants not in good health or have a history of metabolic, cardiovascular, neurological, genetic, endocrine, immune, or physical mobility disorders.
• Participants that had major pregnancy or delivery complications (e.g., preeclampsia/ eclampsia, placenta previa, postpartum haemorrhage, neonatal intensive care, gestational diabetes).
• Participants with substance dependence issues (e.g., nicotine, alcohol, marijuana, illicit drugs).
• Participants that have had breast surgery that may impact lactation, lactogenesis or breastfeeding.
• Participants that use medications that affect lactation (e.g. estrogenic birth control, anti-dopaminergic drugs, Methyldopa) or other continuous prescription medication.
• Participants with a pre-pregnancy BMI below 18 kg/m² or above 28 kg/m².
• Participants who are below 20 years of age or greater than 40 years of age.
• Infants' weight and length are under 3rd or above the 97th percentile, using the World Health Organization (WHO) percentile growth chart.
• Infants born before 38 weeks or after 42 weeks of gestation.
• Infants who use infant formula milk.
• Infants with known metabolic, cardiovascular, neurological, genetic, endocrine, immune, or physical mobility disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Test Lysine Intake; Randomly assigned one of 7 test lysine intakes that range from deficient to excess (12mg/kg/d to 84mg/kg/d). Participants may complete up to 4 study days, at different randomly assigned intakes.

Other: Dietary Lysine Intakes; Participants consume 8 hourly meals that contain the assigned test lysine intake. Each meal will provide one-twelfth of the participants' daily energy requirements as estimated by 1.7 x Resting Energy Expenditure (REE) and adequate protein at 1.5 g.kg.d, to maintain a metabolic steady state. The meals are in the form of a crystalline amino acid protein shake, and nitrogenous free cookies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Carbon 13 Oxidation	Urine and breath samples will be collected to measure the rate of L-[1-13C]phenylalanine oxidation.	8 hours

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Rajavel Elango, University of British Columbia

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Actual): July 17, 2025
• Study Completion (Actual): July 17, 2025

Study Registration Dates

• First Submitted: April 10, 2024
• First Submitted That Met QC Criteria: April 10, 2024
• First Posted (Actual): April 15, 2024

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 28, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Lactation; Stable Isotopes; Indicator Amino Acid Oxidation; Lysine; Dietary Reference Intake; Lysine Requirements
• Other Study ID Numbers: H23-03119

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
• product manufactured in and exported from the U.S.: No