A Pilot Study to Evaluate the Ability of Lactoferrin to Modulate Iron Homeostasis and Exercise Performance in Exercising Females (EFF)

A Pilot Study to Evaluate the Ability of Lactoferrin to Modulate Iron Homeostasis and Exercise Performance in Exercising Females With Compromised Iron Status

This randomized, double-blind, active-controlled trial will evaluate the effects of human lactoferrin supplementation combined with low-dose iron on iron status, aerobic performance, and lactate metabolism in exercising women with low ferritin. Approximately 30 healthy, menstruating women aged 18-45 years with serum ferritin <35 µg/L will be enrolled in an 8-week intervention. Participants will be stratified by baseline ferritin status and randomized to receive 100 mg lactoferrin + 5 mg iron, 300 mg lactoferrin + 5 mg iron, or placebo + 5 mg iron daily.

Primary outcomes include changes in ferritin and hematological parameters. Secondary outcomes include VO₂peak, time to exhaustion, and blood lactate responses during standardized treadmill testing.

This study will determine whether lactoferrin enhances iron homeostasis and improves physiological and performance outcomes in exercising women with low iron stores.

Study Overview

• Status: Recruiting
• Conditions: Iron Deficiency; Exercise Performance of Fit Athletes; Iron Deficiencies; Low Ferritin
• Intervention / Treatment: Dietary supplement: Lactoferrin 100 mg; Dietary supplement: Lactoferrin 300 mg; Dietary supplement: Iron Supplementation (5 mg)

Detailed Description

Iron deficiency is one of the most common micronutrient deficiencies in women, particularly among those who are physically active. Suboptimal iron status can impair oxygen transport, mitochondrial function, and exercise performance. Although oral iron supplementation is commonly used, gastrointestinal side effects may reduce adherence and limit effectiveness. Lactoferrin, an iron-binding glycoprotein, has emerged as a potential adjunct strategy to improve iron regulation and tolerability.

This study will investigate whether supplementation with human recombinant lactoferrin in combination with low-dose iron improves iron status and exercise-related outcomes in exercising women with low ferritin.

Approximately 30 healthy, menstruating women aged 18-45 years with serum ferritin <35 µg/L will be recruited. Participants will be stratified by baseline ferritin status (<20 µg/L or 20-35 µg/L) and randomized in a double-blind, parallel-group design to receive one of the following for 8 weeks:

100 mg lactoferrin + 5 mg iron 300 mg lactoferrin + 5 mg iron Placebo + 5 mg iron Participants will complete six study visits including screening, baseline, and follow-up assessments at weeks 2, 4, 6, and 8. Assessments will include venous blood sampling for iron-related biomarkers and hematological parameters, as well as inflammatory and metabolic markers. Aerobic performance will be evaluated using VO₂peak testing and time-to-exhaustion treadmill protocols with serial blood lactate measurements.

Additional measures include gastrointestinal symptoms, menstrual symptoms, quality of life, and perceived recovery. Daily supplementation compliance and adverse events will be monitored throughout the intervention.

This trial will provide insight into the role of lactoferrin as an adjunct to iron supplementation for improving iron homeostasis and performance outcomes in active women.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anthony M Hagele, MS; Phone Number: 6369494785; Email: ahagele@lindenwood.edu
• Study Contact Backup: Name: Joesi M Morey, MS; Email: jmorey@lindenwood.edu

Study Locations

• United States
  • Missouri
    • Saint Charles, Missouri, United States, 63301
      • Recruiting
      • Exercise and Performance Nutrition Laboratory
      • Principal Investigator: Chad M Kerksick, PhD
      • Contact: Anthony M Hagele, MS; Phone Number: 6369494785; Email: ahagele@lindenwood.edu
      • Contact: Joesi M Morey, MS; Email: jmorey@lindenwood.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Women, 18 - 45 years of age
• No changes in hormonal contraception use in the past 6 months
• Has a regular menstrual cycle defined as five out of the past six months
• Engaging in ≥5 hours per week of structured endurance exercise (e.g., running, cycling, swimming, rowing) for the past ≥6 months, with ≥3 sessions per week at moderate-to-vigorous intensity (≥70% HRmax or RPE ≥13).
• Training must be consistent, with no interruptions >2 consecutive weeks in the past 6 months and performed with the purpose of improving performance or preparing for a competition or personal goal.
• Exhibit some degree of compromised iron status as depicted by serum ferritin levels below 30 ug/L
• Participation in at least one organized endurance event (e.g., races, competitions, or matches) at the recreational, sub-elite, or elite level, or be actively training for a planned competition within the next 6 months.
• Generally healthy and free of diseases or disorders that impact functioning of the gastrointestinal system.
• No recent or acute infection in the past 30 days and no chronic systemic illness
• No psychiatric condition that, in the investigator's judgment, would impair consent capacity, protocol adherence, or valid completion of questionnaires.
• If psychiatric medication is used: stable regimen for ≥3 months with no anticipated changes during the study
• Body mass index (BMI) 18.5 to 32.5 kg/m2 (Inclusive)
• Non-smoker
• Agrees to not use any new vitamin, mineral, or dietary supplement product until after study completion and to not take any vitamins, minerals or dietary supplements 24 hours prior to any of the study visits.
• Willing and able to maintain consistent diet and physical activity habits
• Participants who become pregnant during the course of the study will be removed from participation
• Willing and able to provide consent and comply with the protocol
• Able to read and understand English at the 6th-grade level and sign the informed consent to participate in the study

Exclusion Criteria:

• History of any food allergies or intolerances that could impact digestive outcomes and history of irritable bowel syndrome, inflammatory bowel disease (Crohn's, ulcerative colitis, celiac), gastroparesis, chronic constipation or diarrhea requiring medication, or GI surgery
• Has any of the following medical conditions: bleeding disorders, active heart or cardiovascular disease, uncontrolled high blood pressure (≥ 140/90 mmHg), renal or hepatic impairment/disease, Type I or II diabetes, any neurologic disease or disorder that may impact cognition or mood, unstable thyroid disease, chronic inflammatory conditions, immune disorders (such as HIV/AIDS), or any medical condition deemed exclusionary by the Principal Investigator (PI)
• Acute illness or infection within the past 30 days
• History of cancer (except localized skin cancer without metastases) within 5 years prior to screening.
• Recently started taking (within the past 90 days or has had their dosage adjusted in the past 90 days) antihypertensives, hypoglycemic medications, GLP1 agonists of any class or type, stimulatory asthma medications, or any other prescription or over-the-counter medication that confound the outcomes measured in this study
• Habitual use of anti-inflammatory medications for 30 days prior to providing
• Current or past diagnosis of bipolar I/II disorder, schizophrenia spectrum or other psychotic disorder; psychiatric hospitalization, suicidal ideation, attempt, or self-harm behavior in the past 12 months
• Initiation, discontinuation, or dose change of any psychotropic medication within the past 3 months, including antidepressants, anxiolytics, antipsychotics, mood stabilizers, stimulants, or sedative-hypnotics
• Subject has an allergy to any ingredients in the study product
• Subject has a history of drug or alcohol abuse in the past 12 months
• Excessive alcohol intake defined as greater than 7 drinks/week or binge episodes
• Any condition or abnormality that in the expert opinion of the PI, participation in the study would compromise the safety of the subject or the quality of the study data.
• Participating in or has participated in another research study within 30 days prior to the screening visit that could confound outcomes
• Currently pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-Dose Lactoferrin + Iron; Participants will consume 100 mg human lactoferrin (effera®) combined with 5 mg iron daily for 8 weeks.	Dietary supplement: Lactoferrin 100 mg; Human recombinant lactoferrin administered at a dose of 100 mg daily for 8 weeks.; Dietary supplement: Iron Supplementation (5 mg); Oral iron supplementation provided at a dose of 5 mg daily for 8 weeks.
Experimental: High-Dose Lactoferrin + Iron; Participants will consume 300 mg human lactoferrin (effera®) combined with 5 mg iron daily for 8 weeks.	Dietary supplement: Lactoferrin 300 mg; Human recombinant lactoferrin administered at a dose of 300 mg daily for 8 weeks.; Dietary supplement: Iron Supplementation (5 mg); Oral iron supplementation provided at a dose of 5 mg daily for 8 weeks.
Placebo Comparator: Placebo + Iron; Participants will consume a placebo combined with 5 mg iron daily for 8 weeks.	Dietary supplement: Iron Supplementation (5 mg); Oral iron supplementation provided at a dose of 5 mg daily for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum Ferritin Concentration	Serum ferritin concentration will be assessed via venous blood samples to evaluate changes in iron storage over the intervention period.	Baseline, Weeks 2, 4, 6, and 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hemoglobin	Hemoglobin concentration measured from venous blood samples. Higher values indicate improved oxygen-carrying capacity.	Baseline, Weeks 2, 4, 6, and 8
Change in Hematocrit	Percentage of red blood cells in blood volume. Higher values indicate increased red cell mass.	Baseline, Weeks 2, 4, 6, and 8
Change in Red Blood Cell Count	Total number of red blood cells per unit volume of blood. Higher values indicate increased erythropoiesis.	Baseline, Weeks 2, 4, 6, and 8
Change in Serum Iron	Serum iron concentration measured from venous blood samples.	Baseline, Weeks 2, 4, 6, and 8
Change in Total Iron Binding Capacity	Measure of blood's capacity to bind iron with transferrin.	Baseline, Weeks 2, 4, 6, and 8
Change in Transferrin Saturation	Percentage of transferrin bound to iron. Higher values indicate improved iron availability.	Baseline, Weeks 2, 4, 6, and 8
Change in Hepcidin Concentration	Circulating hepcidin levels reflecting iron regulatory activity. Lower levels generally indicate increased iron availability.	Baseline, Weeks 2, 4, 6, and 8
Change in VO₂Peak	VO₂Peak will be assessed using a graded treadmill test with indirect calorimetry to evaluate maximal aerobic capacity. Higher values indicate improved aerobic performance.	Baseline, Week 4, and Week 8
Change in Time to Exhaustion During Treadmill Testing	Time to exhaustion will be measured during a standardized treadmill protocol. Longer time to exhaustion indicates improved endurance performance.	Baseline, Week 4, and Week 8
Change in Ventilatory Threshold (%VO₂Peak)	Ventilatory threshold will be expressed as a percentage of VO₂Peak during graded exercise testing. Higher values indicate improved submaximal aerobic efficiency.	Baseline, Week 4, and Week 8
Change in Blood Lactate Concentrations During Exercise	Capillary blood lactate will be measured at rest and during standardized treadmill stages (70%, 80%, 85%, and 90% VO₂Peak). Lower lactate at a given workload indicates improved metabolic efficiency.	Baseline, Week 4, and Week 8
Change in Gastrointestinal Symptoms Rating Scale (GSRS) Score	The GSRS is a 15-item questionnaire assessing gastrointestinal symptoms, scored on a 7-point Likert scale (1 = no discomfort, 7 = very severe discomfort). Lower scores indicate fewer symptoms.	Baseline, Week 4, and Week 8
Change in Menstrual Symptoms Questionnaire Score	The MSQ-24 assesses severity and frequency of menstrual-related symptoms. Higher scores indicate greater symptom burden.	Baseline, Week 4, and Week 8
Change in Health-Related Quality of Life (SF-36) Score	The SF-36 evaluates multiple domains of health-related quality of life. Higher scores indicate better perceived health status.	Baseline, Week 4, and Week 8
Change in Perceived Recovery Scale Score	Perceived recovery will be assessed using a 0-10 scale, where 0 indicates very poorly recovered and 10 indicates fully recovered. Higher scores indicate better recovery status.	Baseline, Weeks 2, 4, 6, and 8

Collaborators and Investigators

• Sponsor: Lindenwood University
• Investigators: Principal Investigator: Chad M Kerksick, PhD, Lindenwood University

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: April 15, 2026
• First Submitted That Met QC Criteria: April 15, 2026
• First Posted (Actual): April 23, 2026

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: lactoferrin; time to exhaustion; nutritional supplementation; iron supplementation; menstruating women; ferritin; iron bioavailability; iron metabolism; female athletes; endurance exercise; aerobic performance; effera; vo2peak; lactate metabolism; exercising females
• Additional Relevant MeSH Terms: Metabolic Diseases; Iron Metabolism Disorders; Nutritional and Metabolic Diseases; Iron Deficiencies; Amino Acids, Peptides, and Proteins; Proteins; Carbohydrates; Hydrolases; Enzymes; Enzymes and Coenzymes; Globulins; Glycoproteins; Glycoconjugates; Endopeptidases; Peptide Hydrolases; Serine Endopeptidases; Serine Proteases; Dietary Proteins; Milk Proteins; Animal Proteins, Dietary; Carrier Proteins; Transferrins; Iron-Binding Proteins; Lactoglobulins; Whey Proteins; Metalloproteins; Lactoferrin
• Other Study ID Numbers: IRB-26-88

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared due to privacy and confidentiality considerations. Study results will be reported in aggregate form, and no identifiable data will be disclosed.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No