Exercise Performance of Fit Athletes, Iron Deficiencies, Iron Deficiency, Low Ferritin
Conditions
Keywords
lactoferrin, effera, iron supplementation, iron metabolism, ferritin, aerobic performance, vo2peak, endurance exercise, time to exhaustion, lactate metabolism, female athletes, exercising females, menstruating women, iron bioavailability, nutritional supplementation
Brief summary
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.
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.
Interventions
DIETARY_SUPPLEMENTLactoferrin 100 mg
Human recombinant lactoferrin administered at a dose of 100 mg daily for 8 weeks.
DIETARY_SUPPLEMENTLactoferrin 300 mg
Human recombinant lactoferrin administered at a dose of 300 mg daily for 8 weeks.
DIETARY_SUPPLEMENTIron Supplementation (5 mg)
Oral iron supplementation provided at a dose of 5 mg daily for 8 weeks.
Sponsors
Lindenwood University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Participants and study investigators will be blinded to group assignment. Supplements will be provided in identical-appearing forms and labeled by a third party to ensure concealment of allocation throughout the study.
Intervention model description
Participants will be stratified by baseline ferritin status (\<20 µg/L or 20-35 µg/L) and randomized in a parallel-group design to receive one of three interventions for 8 weeks: (1) 100 mg human lactoferrin + 5 mg iron, (2) 300 mg human lactoferrin + 5 mg iron, or (3) placebo + 5 mg iron. All groups will consume their assigned supplement daily throughout the intervention period.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Ferritin Concentration | Baseline, Weeks 2, 4, 6, and 8 | Serum ferritin concentration will be assessed via venous blood samples to evaluate changes in iron storage over the intervention period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin | Baseline, Weeks 2, 4, 6, and 8 | Hemoglobin concentration measured from venous blood samples. Higher values indicate improved oxygen-carrying capacity. |
| Change in Hematocrit | Baseline, Weeks 2, 4, 6, and 8 | Percentage of red blood cells in blood volume. Higher values indicate increased red cell mass. |
| Change in Red Blood Cell Count | Baseline, Weeks 2, 4, 6, and 8 | Total number of red blood cells per unit volume of blood. Higher values indicate increased erythropoiesis. |
| Change in Serum Iron | Baseline, Weeks 2, 4, 6, and 8 | Serum iron concentration measured from venous blood samples. |
| Change in Total Iron Binding Capacity | Baseline, Weeks 2, 4, 6, and 8 | Measure of blood's capacity to bind iron with transferrin. |
| Change in Transferrin Saturation | Baseline, Weeks 2, 4, 6, and 8 | Percentage of transferrin bound to iron. Higher values indicate improved iron availability. |
| Change in Hepcidin Concentration | Baseline, Weeks 2, 4, 6, and 8 | Circulating hepcidin levels reflecting iron regulatory activity. Lower levels generally indicate increased iron availability. |
| Change in VO₂Peak | Baseline, Week 4, and Week 8 | VO₂Peak will be assessed using a graded treadmill test with indirect calorimetry to evaluate maximal aerobic capacity. Higher values indicate improved aerobic performance. |
| Change in Time to Exhaustion During Treadmill Testing | Baseline, Week 4, and Week 8 | Time to exhaustion will be measured during a standardized treadmill protocol. Longer time to exhaustion indicates improved endurance performance. |
| Change in Ventilatory Threshold (%VO₂Peak) | Baseline, Week 4, and Week 8 | Ventilatory threshold will be expressed as a percentage of VO₂Peak during graded exercise testing. Higher values indicate improved submaximal aerobic efficiency. |
| Change in Blood Lactate Concentrations During Exercise | Baseline, Week 4, and Week 8 | 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. |
| Change in Gastrointestinal Symptoms Rating Scale (GSRS) Score | Baseline, Week 4, and Week 8 | 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. |
| Change in Menstrual Symptoms Questionnaire Score | Baseline, Week 4, and Week 8 | The MSQ-24 assesses severity and frequency of menstrual-related symptoms. Higher scores indicate greater symptom burden. |
| Change in Health-Related Quality of Life (SF-36) Score | Baseline, Week 4, and Week 8 | The SF-36 evaluates multiple domains of health-related quality of life. Higher scores indicate better perceived health status. |
| Change in Perceived Recovery Scale Score | Baseline, Weeks 2, 4, 6, and 8 | 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. |
Countries
United States
Contacts
CONTACTAnthony M Hagele, MS
CONTACTJoesi M Morey, MS
PRINCIPAL_INVESTIGATORChad M Kerksick, PhD
Lindenwood University
Outcome results
None listed