Efficacy of Recombinant Bovine Lactoferrin (rbLf) in Iron Regulation

Overall Objective: To determine the efficacy of rbLf supplementation in a healthy adult population, specifically with regard to iron regulation (primary), gut health (secondary), and immune function (secondary). Purpose: The purpose of this study is to determine the effects of rbLf on iron regulation, exercise performance, gut health, and immune function as compared to cow's milk derived bLf.

Participants: To account for an approximate ~10% dropout rate (and rounding up to ensure equal number of enrolled participants per group), n=25 per group for males (N=50) and n=30 per group for females (N=60) will be enrolled for a total sample size of N=110.

Procedures: Participation in this study will include 6 in-person visits over 14 weeks. Anemia will be checked and excluded at the first visit using a single finger prick, followed by a 10-20 min exercise test on a treadmill to evaluate exercise capacity. On visit 2 participants will perform three 3-15 minute exercise tests on a treadmill with rest in between each test in order to determine exercise performance. A finger prick will be performed before and after each run to determine lactate levels. After visits 2 participants will be randomized to their respective supplement group recombinant Bovine Lactoferrin supplement (rbLf) (Male and Fame), a bovine-milk derived Lactoferrin supplement (Female), or a placebo (Male) once daily for 4 weeks. Blood samples will be obtained prior to and after each supplement phase to determine change in iron levels and red blood cell capacity. After a 2-week washout participants will return to complete the same testing outcomes and will receive the subsequent supplement. At visit 6 a final blood sample will be collected.

Study Overview

• Status: Completed
• Conditions: Exercise Performance
• Intervention / Treatment: Dietary supplement: Recombinant Bovine Lactoferrin; Dietary supplement: Bovine Milk-Derived Lactoferrin; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Applied Physiology Laboratory

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18-42 years
• Body mass index less than 35 kg/m^2

• Finger prick hemoglobin levels fitting within "normal range"

  • Males: 14-18g/dL
  • Females: 12-16g/dL

• Active: meeting American College of Sports Medicine exercise guidelines or exercising more than 2 days per week of

  ● For females specifically:

• Pre-menopausal: experiencing a regular period with no signs of perimenopause or menopause.

Exclusion Criteria:

• Clinically diagnosed iron-deficiency anemia, pagophagia, hemochromatosis, or other blood or iron related medical conditions.
• Allergy or intolerance to milk, egg, soy, peanut, wheat, coconut, or almond dairy
• Smokers or vapers of nicotine or nicotine products
• Immunocompromised or diagnosed with Type I or II diabetes
• Irritable Bowel Disease, Crohn's disease, Celiacs
• Bowel movements less than three times per week, or clinically constipated
• Oral contraceptive users that have combined iron supplementation, or non-monophasic oral contraceptive users.
• Pregnant or nursing
• Chronic eczema or clinically diagnosed asthma.
• Current antibiotic use or antibiotic use within the past 6 weeks
• If flu, corona virus, or cold occurs, subject will remain in the study with their original scheduled visits, but immune values will be excluded.
• Vegan (due to supplement ingredients).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Females: Recombinant Bovine Lactoferrin (rbLf), then Bovine milk derived Lactoferrin; After a 2-week run-in period, this arm will begin treatment with recombinant bovine lactoferrin for 4 weeks and following a 2-week washout start bovine milk derived lactoferrin for 4 weeks.	Dietary supplement: Recombinant Bovine Lactoferrin; Participants will take a single dose equal to 3 capsules daily before a meal for 4 weeks. Meal timing is not controlled.; Dietary supplement: Bovine Milk-Derived Lactoferrin; Participants will take a single dose equal to 3 capsules daily before a meal for 4 weeks. Meal timing is not controlled.
Active Comparator: Females: Bovine milk derived lactoferrin (cmdLf), then Recombinant bovine lactoferrin; After a 2-week run-in period, this arm will begin treatment with bovine milk derived lactoferrin and then following a 2-week washout start recombinant bovine lactoferrin for 4 weeks.	Dietary supplement: Recombinant Bovine Lactoferrin; Participants will take a single dose equal to 3 capsules daily before a meal for 4 weeks. Meal timing is not controlled.; Dietary supplement: Bovine Milk-Derived Lactoferrin; Participants will take a single dose equal to 3 capsules daily before a meal for 4 weeks. Meal timing is not controlled.
Active Comparator: Males: Recombinant Bovine Lactoferrin (rbLf), then placebo; After a 2-week run-in period, this arm will begin treatment with recombinant bovine lactoferrin for 4 weeks and following a 2-week washout start placebo for 4 weeks.	Dietary supplement: Recombinant Bovine Lactoferrin; Participants will take a single dose equal to 3 capsules daily before a meal for 4 weeks. Meal timing is not controlled.; Dietary supplement: Placebo; Participants will take a single dose equal to 3 capsules daily before a meal for 4 weeks. Meal timing is not controlled.; Other Names: Sugar Pill
Placebo Comparator: Males: Placebo, then recombinant bovine lactoferrin (rbLf); After a 2-week run-in period, this arm will begin treatment with placebo for 4 weeks and following a 2-week washout start recombinant bovine lactoferrin for 4 weeks.	Dietary supplement: Recombinant Bovine Lactoferrin; Participants will take a single dose equal to 3 capsules daily before a meal for 4 weeks. Meal timing is not controlled.; Dietary supplement: Placebo; Participants will take a single dose equal to 3 capsules daily before a meal for 4 weeks. Meal timing is not controlled.; Other Names: Sugar Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum iron (mcg/dL)	change in serum blood values obtained before and after supplementation	baseline to 4 weeks
Change in ferritin iron (ng/mL)	change in blood values obtained before and after supplementation	baseline to 4 weeks
Change in red blood cell count (trillion cells/L)	change in blood values obtained before and after supplementation	baseline to 4 weeks
change in iron binding capacity (mcg/dL)	change in blood values obtained before and after supplementation	baseline to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in time to exhaustion running (seconds)	change in treadmill running to exhaustion before and after supplementation	baseline to 4 weeks
change on tumor necrosis factor-a (pg/mL)	change in blood values obtained before and after supplementation	baseline to 4 weeks
change in interleukin-6 (pg/ml)	change in blood values obtained before and after supplementation	baseline to 4 weeks

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: TurtleTree Labs Inc
• Investigators: Principal Investigator: Abbie Smith-Ryan, PhD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2024
• Primary Completion (Actual): July 7, 2025
• Study Completion (Actual): July 7, 2025

Study Registration Dates

• First Submitted: May 20, 2024
• First Submitted That Met QC Criteria: May 20, 2024
• First Posted (Actual): May 24, 2024

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 10, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Iron regulation
• Additional Relevant MeSH Terms: Substandard Drugs; Pharmaceutical Preparations; Carbohydrates; Counterfeit Drugs; Sugars
• Other Study ID Numbers: 23-3039

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 24 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with University of North Carolina. Additionally, clear aims and scope of the data request must be included.
• IPD Sharing Time Frame: 9-24 Months after publication
• IPD Sharing Access Criteria: Clear specific study aims and ethics approval must be present.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

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