Iron Supplementation for Hypoxia

Overseen By Lindsay Forbes, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Colorado, Denver

Must not be taking: Cardiac medications, Pulmonary medications, Anticoagulants, Aspirin

Disqualifiers: Cardiovascular disease, Pulmonary disease, Anemia, Pregnancy, others

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if iron supplements (specifically ferrous sulfate 325mg) can enhance exercise performance in low-oxygen environments. Participants will undergo tests initially without iron and then again after taking iron supplements for 30 days. The trial includes healthy individuals without heart or lung diseases who are not engaged in intense athletic training. Healthy adults not currently taking iron supplements or living at high altitudes might be suitable candidates. As an Early Phase 1 trial, this research seeks to understand how iron supplements function in people, providing an opportunity to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial requires that you do not use cardiac- or pulmonary-related medications, and you must be able to temporarily stop using systemic anticoagulation or aspirin.

Is there any evidence suggesting that ferrous sulfate is likely to be safe for humans?

Research has shown that ferrous sulfate, a common iron supplement, is usually well-tolerated. It often treats low iron levels in the blood, known as iron deficiency anemia. However, like many supplements, it can cause side effects. The most common are stomach upset and diarrhea, which are usually mild and temporary.

Safety data indicates that ferrous sulfate does not pose a cancer risk, which is reassuring. However, it can irritate the skin and eyes, so careful handling is important.

In clinical settings, ferrous sulfate has been used safely for various conditions. Since this study is in its early phase, researchers are still collecting detailed safety information. However, its history of use for anemia provides some confidence in its safety for most people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using ferrous sulfate for hypoxia because it could offer a straightforward and accessible solution to improve oxygen availability in the body. Unlike some current treatments that focus on oxygen delivery systems or medications to stimulate red blood cell production, ferrous sulfate works by directly increasing iron levels, which can enhance the body's natural ability to transport oxygen. This simple approach may help improve exercise capacity and heart function with minimal intervention, making it a promising option for those dealing with hypoxia.

What evidence suggests that this treatment might be an effective treatment for hypoxia?

Research has shown that taking 325mg of ferrous sulfate, an iron supplement, can increase hemoglobin levels in the body. Hemoglobin, a component of red blood cells, carries oxygen. By boosting hemoglobin, iron supplements may enhance oxygen delivery to muscles, potentially improving exercise performance in low-oxygen environments. In this trial, healthy participants will undergo echocardiography and exercise testing before and after 30 days of oral iron supplementation to assess these effects. Studies have found that iron supplements can lower hepcidin, a hormone that regulates iron, and raise transferrin, a protein that transports iron in the blood. This allows the body to use and circulate iron more effectively, which might aid physical performance when oxygen is scarce. Overall, these findings suggest that iron supplements could benefit exercise in low-oxygen conditions. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for premenopausal women aged 18-60 who are not heavily involved in athletic training, do not use heart or lung medications, have not taken iron supplements recently, and don't have anemia or other health conditions that affect exercise ability. They should also not be pregnant or living at high altitudes.

Inclusion Criteria

I am a woman and have not gone through menopause.

Exclusion Criteria

I am on blood thinners or aspirin that can't be stopped for the study.

I am taking medication for heart or lung issues.

You spend more than 9 hours per week doing intense physical activity.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take an oral iron supplement (ferrous sulfate 325 mg oral daily) for 30 days

4 weeks

1 visit (in-person) after treatment

Follow-up

Participants undergo submaximal and maximal exercise testing and echocardiographic measurements to assess the impact of iron supplementation on right ventricular function and exercise performance in hypoxia

1 day

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ferrous sulfate 325mg

Trial Overview The study tests if taking ferrous sulfate (iron) pills can improve how well participants perform physical activities when there's less oxygen available, like at high altitudes.

How Is the Trial Designed?

Group I: Healthy individuals - post-iron Active Control 1 Intervention

The same five healthy participants will complete echocardiography and exercise testing after taking 30 days of oral iron supplementation.

Group II: Healthy individuals - pre-iron Placebo Group 1 Intervention

Five healthy participants will be enrolled. Baseline echocardiography and exercise data prior to oral iron supplementation will be obtained as part of the "parent" study to this study (NCT05272514).

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

In a study involving 22 participants, intravenous iron (ferric carboxymaltose) significantly reduced the rise in pulmonary artery systolic pressure (PASP) during sustained hypoxia by about 50%, and this effect persisted for at least 43 days after administration.

The study suggests that increasing iron stores can have a long-lasting impact on reducing hypoxia-induced pulmonary hypertension, indicating potential therapeutic benefits of intravenous iron in managing certain types of pulmonary hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia. Bart, NK., Curtis, MK., Cheng, HY., et al.[2019]

In a study of 514 pregnant Israeli women, those who took a daily supplement of ferrous sulfate (100 mg elemental iron) experienced significantly less reduction in hemoglobin levels compared to those who did not take the supplement, indicating its efficacy in preventing anemia during pregnancy.

Despite the benefits, 40 out of the 200 women on the iron supplement developed anemia after the fifth month, suggesting that while the supplement is helpful, monitoring is necessary as pregnancy progresses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anemia of pregnancy: evaluation of the effectiveness of routine dietary supplementation program in an Israeli community. Palgi, A., Levi, S., Reshef, A.[2019]

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]

Iron supplementation (100 mg/day) significantly improved hemoglobin levels and antioxidant enzyme activity in 117 anemic women over 100 days, indicating its efficacy in treating iron deficiency anemia.

However, the treatment also increased oxidative stress markers and caused more side effects in women with mild anemia compared to those with moderate or severe anemia, suggesting that iron supplementation should be tailored to individual needs rather than given universally.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral iron supplementation leads to oxidative imbalance in anemic women: a prospective study. Tiwari, AK., Mahdi, AA., Chandyan, S., et al.[2013]

In a study of 187 pregnant women with iron deficiency anemia, those treated with ferrous bis-glycinate experienced a significantly greater increase in hemoglobin levels (2.48 g/dL) compared to those receiving ferrous glycine sulfate (1.32 g/dL) after 8 weeks.

Ferrous bis-glycinate not only proved to be more effective, with 89.2% of women reaching hemoglobin levels above 11 g/dL, but also had a better safety profile, as the rate of adverse effects was significantly higher in the ferrous glycine sulfate group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of ferrous bis-glycinate versus ferrous glycine sulfate in the treatment of iron deficiency anemia with pregnancy: a randomized double-blind clinical trial. Abbas, AM., Abdelbadee, SA., Alanwar, A., et al.[2020]

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]

Citations

1. withpower.com withpower.com/trial/early-phase-1-hypoxia-4-2022-8eeae

Iron Supplementation for Hypoxia · Info for Participants Ferrous sulfate 325mg is unique because it provides a high dose of elemental iron, which can help increase hemoglobin levels, potentially improving oxygen ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10719729/

Iron Supplements Concomitant within Hypoxia-Inducible ... Most HIF-PHI trials revealed a significant decline of hepcidin, increase in transferrin level and total iron binding capacity in patients. From a clinical point ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7193469/

Iron absorption from supplements is greater with alternate day ... In this study, for both iron doses, SHep was significantly higher with consecutive day doses (on day 3 compared to day 2, P<0.01) and significantly lower with ...

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

Oral iron supplementation in iron-deficient women Traditionally, the recommended daily dose is 100–200 mg iron per day given as three or four divided doses of ferrous salts: e.g., a 325 mg ferrous sulfate ...

5. emedicine.medscape.com emedicine.medscape.com/article/202333-treatment

Iron Deficiency Anemia Treatment & Management Oral ferrous iron salts are the most economical and effective medication for the treatment of iron deficiency anemia. Of the various iron salts ...

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

Ferrous Sulfate: Uses, Dosage & Side Effects Ferrous sulfate is used to treat iron deficiency anemia. Includes ferrous sulfate side effects, interactions and indications.

7. fishersci.com fishersci.com/store/msds?partNumber=S25325A&productDescription=FERROUS+SULFATE+GR+500G+5HYD&vendorId=VN00115888&countryCode=US&language=en

Safety Data Sheet 7782-63-0 Ferrous sulfate heptahydrate 1000 lb. Proposition 65 (California): Chemicals known to cause cancer: None of the ingredients are listed ...

8. sigmaaldrich.com sigmaaldrich.com/US/en/sds/SIGMA/F8263?srsltid=AfmBOorDJv727aKBw7Y39wIRZHzFXLk1BX8HH4CLzkAIBwkTNtpCrBoB

SAFETY DATA SHEET Hazard Statements. H302. Harmful if swallowed. H315. Causes skin irritation. H319. Causes serious eye irritation. Precautionary Statements. P264.

9. nj.gov nj.gov/health/eoh/rtkweb/documents/fs/0931.pdf

Hazardous Substance Fact Sheet FERROUS SULFATE. Page 2 of 6. Determining Your Exposure. ▻ Read the product manufacturer's Material Safety Data. Sheet (MSDS) and the label to determine product.