Iron Supplements for Iron Deficiency

Overseen By Lauren Hundseth

Age: < 65

Sex: Female

Trial Phase: Academic

Sponsor: University of Calgary

Must not be taking: Antibiotics, Antacids, NSAIDs, others

Disqualifiers: Anemia, Smoking, Alcohol, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if different types and doses of iron supplements (ferrous sulfate) can boost iron levels, improve athletic performance, and support gut health in young female athletes with low iron. It will compare the effectiveness and stomach comfort of low-dose yeast-bound iron, low-dose traditional iron, and high-dose iron. Participants will take one of these supplements, undergo fitness tests, and provide samples to assess their body's response. Ideal candidates are biologically female athletes who train at high levels and have low iron stores but no major health issues. As an unphased trial, this study offers participants the chance to contribute to valuable research that could enhance athletic performance and overall health.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that affect iron absorption, like antacids and some antibiotics, at least 3 months before joining. If you're on medications affecting exercise responses, like beta-blockers, you may also need to stop. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In previous studies, people taking high doses of iron (over 45 mg a day) often reported stomach issues such as nausea, constipation, and changes in bowel movements. Some even experienced black stools and had to stop taking the iron due to these problems. High doses of iron can be harmful and require careful use.

Low-dose iron supplements, providing up to 40 mg a day, usually cause milder side effects. They are considered safe for most people, though mild stomach discomfort can still occur.

Yeast-bound iron is a newer form designed to reduce stomach problems. While research is limited, early findings suggest it might be gentler on the stomach compared to traditional iron pills.

Overall, those considering joining a trial should know that low-dose iron options and yeast-bound iron could be easier on the digestive system. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for iron deficiency because they offer potential improvements over standard iron supplements. The yeast-bound iron supplement, in particular, is noteworthy due to its unique delivery method. It combines iron with inactivated nutritional yeast, which could enhance absorption and reduce common gastrointestinal side effects associated with traditional iron supplements. Additionally, exploring both low and high doses of iron allows for a tailored approach to treatment, which could lead to more personalized and effective care for individuals with iron deficiency. These innovative approaches might enhance patient compliance and overall outcomes.

What evidence suggests that this trial's iron supplements could be effective for improving iron levels and athletic performance in young female athletes?

This trial will compare different iron supplements for treating iron deficiency. Research has shown that oral iron pills can effectively treat low iron levels. Participants may receive a low dose of iron, which studies have found can significantly increase important blood markers like hemoglobin and ferritin. Another group will receive a high dose of iron, typically between 150-200 mg, often recommended for treating iron deficiency anemia. Additionally, the trial will evaluate a low dose of yeast-bound iron, which ongoing research suggests might be gentler on the stomach and cause fewer side effects. Overall, these iron supplements have shown promise in boosting iron levels and alleviating symptoms of iron deficiency. ^{3 4 6 7 8}

Who Is on the Research Team?

Jane Shearer

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

This trial is for young female athletes aged 16-35 who have low iron stores, potentially affecting their performance. They must be willing to take iron supplements, undergo fitness tests, and provide blood, stool, and intestinal samples. Athletes should not participate if they have conditions that could interfere with the study or are unable to comply with its requirements.

Inclusion Criteria

Complete and pass the Get Active Questionnaire (GAQ)

Suboptimal ferritin levels (≤50 mcg/L)

Provide informed consent to participate in study

Exclusion Criteria

I am currently using laxatives.

My BMI is between 16 and 30.

I have been taking iron supplements in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Testing

Participants undergo baseline testing including blood draw, DXA scan, VO2 max test, and anaerobic performance testing

1 week

2 visits (in-person)

Treatment

Participants take assigned iron supplements every other day for 12 weeks and complete regular surveys

12 weeks

1 visit (in-person) every 4 weeks

Follow-Up

Participants are monitored for changes in iron status, gut microbiota, and athletic performance

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• High-dose iron (ferrous sulfate)
• Low-dose iron (ferrous sulfate)
• Yeast-bound iron (ferrous sulfate)

Trial Overview The trial is testing three types of oral iron supplements: a high-dose (150 mg), a low-dose (40 mg), and a low-dose yeast-bound version (40 mg). It aims to determine which improves iron levels and athletic performance while being gentle on the gut over a period of 12 weeks.

How Is the Trial Designed?

Group I: Low dose iron supplement bound to yeast Experimental Treatment 1 Intervention

Low dose iron (40 mg elemental iron) in the form of yeast-bound iron, specifically Lalmin® Fe10. This supplement consists of encapsulated ferrous sulphate complexed with inactivated Saccharomyces cerevisiae (nutritional yeast).

Group II: Low dose iron supplement Active Control 1 Intervention

This supplement consists of encapsulated ferrous sulphate (40 mg elemental iron).

Group III: High dose iron supplement Active Control 1 Intervention

This supplement consists of encapsulated ferrous sulphate (150 mg elemental iron).

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Mitacs

Industry Sponsor

Trials

46

Recruited

5,200+

Natural Sciences and Engineering Research Council, Canada

Collaborator

Trials

63

Recruited

3,000+

Published Research Related to This Trial

In a 12-week study involving 72 participants with uncomplicated iron deficiency anemia, a ferrous iron supplement (Ferall) was found to be significantly more effective than a ferric iron polysaccharide complex (Niferex) in improving hemoglobin and serum ferritin levels.

While the ferrous product was associated with a slightly higher frequency of gastrointestinal side effects, both supplements were well tolerated, and no participants withdrew due to side effects, indicating that the ferrous product is safe and effective for treating iron deficiency anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of a combination ferrous fumarate product and a polysaccharide iron complex as oral treatments of iron deficiency anemia: a Taiwanese study. Liu, TC., Lin, SF., Chang, CS., et al.[2019]

Ferrous salts, specifically ferrous fumarate, gluconate, and sulfate, are commonly used and well-tolerated oral treatments for iron deficiency anemia, which is a frequent health issue.

Mössbauer spectroscopy and X-ray powder diffraction techniques were used to analyze these ferrous salts, revealing that ferrous fumarate and gluconate contain about 10% ferric iron, and providing the first reported Mössbauer spectrum for ferrous fumarate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Mössbauer and X-ray powder diffraction study of some ferrous hematinics. Coe, EM., Bowen, LH., Bereman, RD.[2019]

The 'Safe Iron Study' is the first clinical trial to evaluate the safety and efficacy of novel iron supplements, comparing them to traditional ferrous sulfate in healthy adults, aiming to address the adverse effects associated with current iron treatments.

The study will assess whether these new iron forms can improve iron status without increasing risks of malaria, bacterial infections, or gut inflammation, potentially leading to safer options for treating iron deficiency and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe and effective delivery of supplemental iron to healthy older adults: The double-blind, randomized, placebo-controlled trial protocol of the Safe Iron Study. Lewis, ED., Wu, D., Mason, JB., et al.[2023]

Oral iron supplementation with ferrous sulfate (FeSO₄) leads to significantly higher levels of non-transferrin-bound iron (NTBI) in the bloodstream compared to other iron compounds, which raises safety concerns for young children with malaria.

In contrast, iron compounds like sodium iron ethylenediaminetetraacetic acid (NaFeEDTA) and iron polymaltose show negligible NTBI responses, suggesting they may be safer alternatives for iron supplementation in areas where malaria is prevalent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral administration of ferrous sulfate, but not of iron polymaltose or sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), results in a substantial increase of non-transferrin-bound iron in healthy iron-adequate men. Schümann, K., Solomons, NW., Romero-Abal, ME., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4294008/

Effects of iron supplementation twice a week on attention ... Oral iron supplements (50 mg twice a week for 16 weeks) were able to improve the attention span and haematologic indices of female high school students.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0098299720300364

Oral iron supplementation in iron-deficient women Oral iron supplementation can be an effective strategy to treat and prevent IDA, but guidelines vary. Some experts recommend doses of 150–200 mg elemental iron ...

3. amjmed.com amjmed.com/article/S0002-9343(05)00210-X/fulltext

Are we giving too much iron? Low-dose iron therapy is ... After ingestion of 15 mg of iron, serum iron concentration rose significantly in all iron-deficiency anemia patients, beginning 15 minutes after iron intake (P ...

4. gastrojournal.org gastrojournal.org/article/S0016-5085(06)00480-X/fulltext

Treatment of iron deficiency The authors found that iron absorption rose significantly in the anemic patients beginning minutes after the first dose (there was no increase in iron ...

5. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00463-7/fulltext

Alternate day versus consecutive day oral iron ... Co-primary outcomes, at equal total iron doses, were serum ferritin and gastrointestinal side effects; secondary outcomes were iron deficiency ...

6. drugs.com drugs.com/ferrous_sulfate.html

Ferrous Sulfate: Uses, Dosage & Side Effects An overdose of iron can be fatal, especially in a young child. Overdose symptoms may include nausea, severe stomach pain, bloody diarrhea, ...

7. ods.od.nih.gov ods.od.nih.gov/factsheets/Iron%20-HealthProfessional/

Iron - Health Professional Fact Sheet High doses of supplemental iron (45 mg/day or more) may cause gastrointestinal side effects, such as nausea and constipation [5]. Other ...

8. webmd.com webmd.com/diet/supplement-guide-iron

Iron Supplements for Anemia At high doses, iron can be toxic. For healthy adults and children ages 14 and up, the upper limit experts recommend is 45 milligrams a day. ( ...