Effects of Iron Supplementation on Skeletal Muscle Properties in Females With Suboptimal Iron Storage

NCT07084298 | Not Yet Recruiting Early Phase 1

• 1 other identifier: REB25-0927
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn whether oral iron supplementation will increase skeletal muscle iron storage and its effects on exercise capacity in females with suboptimal iron status. The study will include healthy females, ages 18-40, who either have suboptimal or optimal iron stores. The main questions it aims to answer are:

• Does iron supplementation increase skeletal muscle iron storage and alter the expression of iron-related and mitochondrial proteins?
• Does iron supplementation improve single-leg exercise performance?
• Is serum ferritin correlated with the abundance of iron-related proteins in skeletal muscle? Researchers will compare outcomes from females with suboptimal iron status who receive oral iron supplementation to those who receive a placebo to see if supplementation improves muscle iron storage, protein expression, and exercise performance. Additionally, a non-intervention control group with optimal iron status will be included to assess baseline differences. Participants will: \- Be randomly assigned to receive 150 mg elemental iron or placebo (maltodextrin) every other day for 12 weeks Complete pre- and post-supplementation testing, including:
• Blood draws to assess iron status
• Skeletal muscle biopsies to analyze protein content
• Whole-body and single-leg exercise tests to assess performance
• Controls will undergo baseline-only testing to compare physiological and biochemical markers

Conditions

Iron Deficiency

Keywords

iron; iron deficiency; athletic performance; female athlete; iron supplements; ferritin; hemoglobin; muscle; muscle ferritin; mitochondria; critical power; aerobic fitness; exercise; placebo

Outcome Measures

Primary Outcomes (1)

• Muscle Ferritin

  Muscle collection: The muscle biopsy involves the removal of a small piece of muscle tissue from the vastus lateralis using a sterile hollow needle. The area over the incision site will be carefully cleaned, and a small amount of local anesthetic will be injected into and under the skin. A small, 4 - 5 mm incision will be made in the skin to create an opening for the biopsy needle. The biopsy needle will then be inserted through the incision into the muscle, and a small piece of muscle (\~50 mg) will be removed, and the needle taken out. A medical doctor will perform this procedure. Protein analysis: Western blotting will be used to analyze the abundance of ferritin within small sections of the muscle sample.

  At baseline (week 0) and completion of supplementation (week 12)

Secondary Outcomes (7)

• Serum iron status

  Every four weeks beginning at baseline (week 0) until completion of supplementation (week 12)

• Iron-related proteins

  At baseline (week 0) and completion of supplementation (week 12)

• Mitochondrial proteins

  At baseline (week 0) and completion of supplementation (week 12)

• Whole body aerobic fitness (VO2max)

  At baseline (week 0) and completion of supplementation (week 12)

• Single-leg critical power

  At baseline (week 0) and completion of supplementaton (week 12)

Study Arms (2)

Iron supplement

EXPERIMENTAL

Dietary supplement: Oral iron supplement, encapsulated ferrous sulphate (150mg elemental iron)

Dietary Supplement: Oral iron supplement

Placebo

PLACEBO COMPARATOR

Placebo control: Sugar pill, encapsulated polysaccharide substance (malodextrin)

Other: Placebo

Interventions

Oral iron supplement DIETARY_SUPPLEMENT

Encapsulated ferrous sulphate (150mg elemental iron)

Iron supplement

Placebo OTHER

Encapsulated polysaccharide (maltodextrin)

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• biologically female
• between the ages of 18-40 years of age at the time of enrolment
• plasma ferritin ≤ 50 µg/ L (RCT) or \>50 µg/L (controls)
• complete Get Active Questionnaire (GAQ: Canadian Society for Exercise Physiology) without contraindication

You may not qualify if:

• have a body mass index (BMI) \> 30 kg/m2
• taking medications that have been shown to affect cardiovascular, respiratory, or metabolic responses to exercise (e.g., β-blockers, anti-inflammatories, anti-coagulants, insulin, etc.)
• hemoglobin ≤ 120 g/L (anemia cut-off for women)
• have known health problems or contraindications that prohibit exercise, including renal or gastrointestinal disorders, metabolic disease, heart disease, vascular disease, arthritis, diabetes, respiratory disease, uncontrolled blood pressure, dizziness, thyroid problems, or any other health conditions that are being treated and deemed likely to confound the results
• dieting for weight loss or following a low-carbohydrate diet (known to affect iron homeostasis)
• history of smoking or using tobacco products
• consuming excessive amounts of alcohol (\>21 units/week)
• supplementing with iron (\>5mg/day) in the last 3 months
• any blood donation or surgeries in the past 3 months
• antibiotic use within the previous four weeks before study enrolment
• current laxative use
• known history of thalassemia
• known bleeding disorder
• chronic use of nonsteroidal anti-inflammatory drugs
• Currently/last 3 months taking prescription medications that are known to affect iron absorption (i.e. Antacids/PPIs (e.g., omeprazole), H2 Blockers (e.g., ranitidine), Tetracycline Antibiotics (e.g., doxycycline), Quinolone Antibiotics (e.g., ciprofloxacin), Cholestyramine, Colchicine, Methyldopa).

Sponsors & Collaborators

• University of Calgary: lead
• Natural Sciences and Engineering Research Council, Canada: collaborator

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

Location

Related Publications (20)

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• Moretti D, Goede JS, Zeder C, Jiskra M, Chatzinakou V, Tjalsma H, Melse-Boonstra A, Brittenham G, Swinkels DW, Zimmermann MB. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood. 2015 Oct 22;126(17):1981-9. doi: 10.1182/blood-2015-05-642223. Epub 2015 Aug 19.

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• MacInnis MJ, Zacharewicz E, Martin BJ, Haikalis ME, Skelly LE, Tarnopolsky MA, Murphy RM, Gibala MJ. Superior mitochondrial adaptations in human skeletal muscle after interval compared to continuous single-leg cycling matched for total work. J Physiol. 2017 May 1;595(9):2955-2968. doi: 10.1113/JP272570. Epub 2016 Aug 3.

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• Stugiewicz M, Tkaczyszyn M, Kasztura M, Banasiak W, Ponikowski P, Jankowska EA. The influence of iron deficiency on the functioning of skeletal muscles: experimental evidence and clinical implications. Eur J Heart Fail. 2016 Jul;18(7):762-73. doi: 10.1002/ejhf.467. Epub 2016 Jan 21.

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• Melenovsky V, Hlavata K, Sedivy P, Dezortova M, Borlaug BA, Petrak J, Kautzner J, Hajek M. Skeletal Muscle Abnormalities and Iron Deficiency in Chronic Heart FailureAn Exercise 31P Magnetic Resonance Spectroscopy Study of Calf Muscle. Circ Heart Fail. 2018 Sep;11(9):e004800. doi: 10.1161/CIRCHEARTFAILURE.117.004800.

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• McDougall RM, Tripp TR, Frankish BP, Doyle-Baker PK, Lun V, Wiley JP, Aboodarda SJ, MacInnis MJ. The influence of skeletal muscle mitochondria and sex on critical torque and performance fatiguability in humans. J Physiol. 2023 Dec;601(23):5295-5316. doi: 10.1113/JP284958. Epub 2023 Oct 30.

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• Dietz JV, Fox JL, Khalimonchuk O. Down the Iron Path: Mitochondrial Iron Homeostasis and Beyond. Cells. 2021 Aug 25;10(9):2198. doi: 10.3390/cells10092198.

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• Brownlie T 4th, Utermohlen V, Hinton PS, Giordano C, Haas JD. Marginal iron deficiency without anemia impairs aerobic adaptation among previously untrained women. Am J Clin Nutr. 2002 Apr;75(4):734-42. doi: 10.1093/ajcn/75.4.734.

  PMID: 11916761 BACKGROUND

• Brutsaert TD, Hernandez-Cordero S, Rivera J, Viola T, Hughes G, Haas JD. Iron supplementation improves progressive fatigue resistance during dynamic knee extensor exercise in iron-depleted, nonanemic women. Am J Clin Nutr. 2003 Feb;77(2):441-8. doi: 10.1093/ajcn/77.2.441.

  PMID: 12540406 BACKGROUND

MeSH Terms

Conditions

Iron Deficiencies; Motor Activity

Interventions

Iron-Dextran Complex

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Behavior

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Dextrans; Glucans; Polysaccharides; Carbohydrates

Study Officials

• Martin J MacInnis

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexander L Isidori

CONTACT

6475173560; alex.isidori1@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 16, 2025
• First Posted: July 24, 2025
• Study Start: August 1, 2025
• Primary Completion: May 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: August 6, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)