Overview
The goal of this clinical trial is to learn if different types and doses of oral iron supplements can improve iron levels, athletic performance, and gut health in young female athletes with low iron stores. The main questions it aims to answer are:
- Does a low dose of yeast-bound iron improve iron status better than traditional iron supplements?
- Do the different iron supplements cause fewer or more gastrointestinal (stomach) symptoms?
- How do iron supplements affect exercise performance and gut bacteria?
Researchers will compare three types of iron supplements:
- A low-dose iron supplement (40 mg)
- A low-dose yeast-bound iron supplement (40 mg)
- A high-dose iron supplement (150 mg)
This will help researchers find out which type of supplement is most effective and easiest on the stomach.
Participants will:
- Take one of the three assigned iron supplements every other day for 12 weeks
- Complete fitness tests before and after the study, including cycling and jumping tests
- Give blood samples to measure iron levels
- Provide stool and intestinal samples to study gut bacteria
- Swallow a SIMBA capsule before and after the study to collect a sample from the small intestine
- Complete regular online surveys about sleep, stress, menstrual cycles, and gut symptoms
Description
This clinical trial is designed to evaluate and compare the effects of three oral iron supplementation strategies on iron status, gut microbiota, and athletic performance in young female athletes with suboptimal iron levels. The study compares a low-dose iron supplement, a low-dose yeast-bound iron supplement (Lalmin® Fe10), and a high-dose iron supplement. The primary goal is to identify which iron supplement improves iron status most effectively while minimizing gastrointestinal symptoms and changes to the gut microbiota.
The rationale for the study is based on the high prevalence of iron deficiency among female athletes, especially those involved in endurance and high-intensity sports. Iron plays a key role in oxygen transport, energy production, and recovery, making it essential for optimal athletic performance. However, current supplementation practices often lead to poor compliance due to side effects and low absorption rates. The yeast-bound iron product being tested is hypothesized to improve absorption and tolerability by altering the site of absorption and reducing gastrointestinal distress.
Participants will be biologically female athletes aged 16-35 with suboptimal ferritin (≤50 µg/L), who are competitively trained and meet strict health and fitness criteria. After screening, eligible participants will be randomly assigned to one of three groups and consume their assigned supplement every other day for 12 weeks. Each supplement will be encapsulated to preserve blinding and consistency.
The study involves six in-person visits:
Visit 1 Screening and Consenting:
Study investigators will reach out electronically or by phone to individuals interested in participating in the study. At this time, participants will be informed about the study and eligibility will be confirmed. Iron status will be assessed using ferritin, achieved through a forearm venipuncture. Participants with suboptimal ferritin levels (≤50 µg/L) will be asked to complete a 3-day food record over the following week on non-consecutive days. This food intake data will be used to determine energy availability to ensure participants meet the minimum requirement of \>30 kcal/kg lean body mass. Those who do not meet this requirement will be excluded from further participation.
Visit 2 Baseline Testing (Week 0):
Once inclusionary criteria has been confirmed and met, participants will undergo baseline measures of iron status through a forearm blood draw, they will complete a body composition assessment to assess lean body mass, and participants will complete a cycling-based aerobic fitness test (VO2 max) to characterize their fitness level. Participants will also be sent home with a package with SIMBA capsules, fecal sample collection kit, and collection instructions.
Visit 3 Baseline Testing (Week 0):
Participants will return 48-72 hours later to complete a cycling-based anaerobic fitness test (Wingate) and a countermovement jump test to assess fitness level. After fecal sample has been retrieved and picked up by study personal, participants will begin the 12-week nutritional intervention.
Nutritional Intervention:
Participants will consume an oral iron supplement every other day for 12 weeks. Participants will take their supplement within 30 minutes of morning training. If there is no morning training, participants will be instructed to consume immediately upon waking. The total dose of elemental iron is 40mg for the low dose group, 40mg for the yeast bound iron group, and 150mg for the high dose group, contained within a gelatin capsule. The iron-complexed yeast is a pasteurized (not live) Saccharomyces cerevisiae, a common nutritional yeast. There are no limits on how much can be consumed. They will also be reminded to take with food, a few hours before or after taking other medications or natural health products and avoid coffees, teas, dairy and dairy alternatives for two hours after consumption every other day. If they miss a dose, they will be recommended to take the next dose the next day and begin dosing every other day from there. After 4 and 8 weeks of consuming the supplement, participants will return to the lab for follow-up testing, consisting of a venipuncture blood draw (visits 4 and 5) and three-day food log (visit 4 only). At these visits they will be provided with another four-week supply of capsules. Participants will then be instructed to return to the lab to retrieve another 4 weeks of capsules, 8 weeks into the intervention, before completing their 12-week post-intervention tests. The Get Active Questionnaire (GAQ) and Menstrual Disorder of Teenagers (MDOT) will be completed at baseline; the Epworth Sleepiness Scale and Menstrual Bleeding Questionnaire will be completed monthly; the Gastrointestinal Symptoms Questionnaire, Post Exercise Short Recovery Scale, and Acute Recovery and Stress Scale will be assessed weekly through Qualtrics, an online survey platform.
Visit 4 Follow-Up (Week 4):
Participants will have a blood sample drawn for assessment of iron status and be instructed to complete a 3-day food log on three-non-consecutive days over the next week.
Visit 5 Follow-Up (Week 8):
Participants will have a blood sample drawn for assessment of iron to reduce the risk of iron overload.
Visit 6 Post Intervention (Week 12):
After the 12-week intervention has concluded, participants will return to the lab to repeat the aerobic exercise test (VO2).
Visit 7 Post Intervention (Week 12):
Participants will return to the lab to repeat measures done at baseline (blood status, body composition, anaerobic fitness test (Wingate and countermovement jump test), 3-day food log, fecal sample collection kit, and SIMBA capsule). At this time, participants will return any unused capsules to be counted for assessment of compliance.
Primary outcomes include changes in markers of iron status (ferritin, hemoglobin, RBC indices). Secondary outcomes include aerobic/anaerobic performance measures, body composition (DXA), substrate metabolism, gut microbiota composition (via fecal and intestinal sampling), and self-reported gastrointestinal symptoms. Safety and tolerability will be monitored at each study visit and through participant self-report.
Data will be analyzed using both traditional statistics (e.g., ANOVA) and machine learning methods for complex 'omics' data. Results will inform better supplementation strategies for female athletes and will be shared through academic publications.
The study will contribute to a greater understanding of iron supplementation strategies that are effective, tolerable, and beneficial to performance and health.
Eligibility
Inclusion Criteria:
- Biologically female athlete
- Age 16-35
- At least one year past the age of menarche
- Complete and pass the Get Active Questionnaire (GAQ)
- Suboptimal ferritin levels (≤50 mcg/L)
- Provide informed consent to participate in study
- Activity level based on Participant Classification Framework (McKay et al., 2022)
- Tier 3: Highly Trained / National Level
- Tier 4: Elite / International Level
- Energy availability \>30 kcal/kg LBM
- Have access to a smartphone, tablet, or computer
- Able to swallow a capsule sized 25mm length and 8mm width (i.e. large dose omega 3 pill)
Exclusion Criteria:
- Non-English speaking
- Anemic (hemoglobin \<120g/L)
- Regular prebiotic (fiber) or probiotic use within 4 weeks of study enrollment
- Current laxative use
- Are a smoker or use tobacco products
- Consume \>21 units of alcohol per week
- Have donated blood in the previous 3 months
- Have a BMI \<16 but \>30kg/m2
- Are dieting for weight loss or are following a low carbohydrate diet
- Have participated in another clinical trial within the 30 days preceding study enrollment.
- Known allergy of hypersensitivity to any ingredient, including non-medicinal ingredients, such as iron, yeast, cellulose, or maltodextrin
- Are taking medications known to affect cardiovascular or metabolic responses to exercise such as beta-blockers, anti-coagulants etc. as assessed by the Principal Investigator
- Known history of thalassemia or thalassemia trait
- Known inherited bleeding disorder
- Major surgery in the past 3 months
- Chronic use of Salicylates, aspirin, corticosteroids, or nonsteroidal anti-inflammatory drugs
- Have any of the following conditions: renal or gastrointestinal disorders, autoimmune disease, metabolic disease, heart disease, vascular disease, rheumatoid arthritis, diabetes, poor lung function, uncontrolled blood pressure, dizziness, thyroid problems, or any other health conditions that are being treated and deemed to be able to significantly interfere with study intervention and assessment in the opinion of the Principal Investigator and Qualified Investigator
- Have current musculoskeletal injuries that limit exercise capacity
- Self-identifying with any kidney or gastrointestinal issues, metabolic disorders, cardiac conditions, vascular illnesses, rheumatoid arthritis, diabetes, compromised lung function, unregulated blood pressure, episodes of dizziness, thyroid complications, or any other health conditions under treatment that might potentially interfere with the study results
- Orthopaedic issues that limit exercise ability
- 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.)
- Currently taking levodopa or levothyroxine
- Currently/last 3 months taking iron containing supplements
- Are pregnant or lactating or planning to become pregnant for the duration of the study. All participants must agree to use a medically approved method of birth control for the duration of the study. All hormonal birth control must have been in use for a minimum of three months. Acceptable methods of birth control include:
- Abstinence or agrees to use contraception if planning to become sexually active
- Hormonal contraceptives including oral contraceptives, hormone birth control patch
- Vaginal contraceptive ring, injectable contraceptives, or hormone implant
- Barrier methods (e.g. condoms with spermicide, diaphragms with spermicide)
- Intrauterine devices
- Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s)
- Vasectomy of partner at least 6 months prior to screening
Additional exclusion criteria based on use of SIMBA capsules. Following is a summary of SIMBA capsules specific exclusion criteria:
- Currently pregnant, planning to become pregnant, or breastfeeding
- Prior gastrointestinal disease, surgery, or radiation treatment which, in the Investigator's opinion, would lead to intestinal structuring, narrowing, or obstruction with a risk of capsule non-excretion, including, e.g. achalasia, eosinophilic esophagitis, any IBD, or previous esophageal, gastric, small intestinal, or colonic surgery. Appendectomy or cholecystectomy more than 3 months before the screening visit is acceptable.
- History of known structural gastrointestinal abnormalities such as structures or fistulas leading to mechanical obstruction
- Have any gastrointestinal inflammatory diseases, including ulcerative colitis, Crohn's disease, microscopic colitis.
- Use of any medication in the week prior to the screening study visit, unless part of regular treatment, that could substantially alter gastrointestinal motor function (e.g. opioids, prokinetics, anticholinergics, GLP-1 analogues); laxative use is allowed if it is kept unchanged in the week prior to the study visit. Proton pump inhibitors (PPIs) are allowed provided a wash-out period of 48 hours is respected before swallowing the SIMBA capsules and PPI treatment is resumed only 4 hours thereafter.
- Prokinetic (stimulate muscle contractions, Metoclopramide, Domperidone, Prucalopride, etc.) use. If you are not using prokinetics to treat SIBO, then you may be eligible after a 2-week washout period, and willing to not use prokinetics for the study duration.
- Unable to stop using laxatives or prokinetic medications for 4 days before the study procedure (breath test). Laxatives can be resumed after the test is conducted.
- Have used antibiotics (except for topical use) in the previous 12 weeks. You may be eligible to participate once a 12-week washout is completed
- Regular use of probiotics, prebiotics, or synbiotics (including food and drinks containing added probiotics and/or probiotic yogurts with live, active cultures)
- Have digestive problems that slow or stop food from moving properly, like a slow stomach, blocked intestines, or stiffened tissues
- Suffer from celiac disease (treated or untreated)
- Organic motility disorder, including gastroparesis, intestinal pseudo-obstruction, systemic sclerosis, Ogilvie's syndrome
- History of oropharyngeal dysphagia, or other swallowing disorder with a risk of capsule aspiration
- Have had a cancer diagnosis or treatment within the past year (non-melanoma skin cancers are acceptable)
- Have trouble swallowing, which could cause a risk of choking on a capsule
- Participants scheduled for an MRI at any time during the study. You may be eligible to participate once your MRI procedure is completed.
- Have constant constipation (IBS-C) defined as a history of less than 3 bowel movements per week
- Any prior fecal microbiota transplantation
- Drug use
- Suffer from alcohol or drug abuse
- Females of childbearing potential will be asked about their likelihood of being pregnant, based on factors such as recent sexual activity or use of contraception. Their self-reported confirmation of non-pregnancy will be accepted unless they express uncertainty. In cases of doubt, a urine beta-HCG pregnancy test will be required for confirmation. If you become pregnant during the course of the study, you should stop taking the supplement immediately and inform the investigators. If you are using a supplement that the investigators have deemed to not interfere with the study's intervention or assessment (e.g. vitamins, omega-3, creatine monohydrate etc.), you will be permitted to continue taking these supplements. In all cases, participants will be instructed to not change the dose of the taken supplement or introduce a new supplement unless it is medically recommended.
