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

5 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if taking iron supplement pills improves exercise performance in low-oxygen conditions.

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.

What data supports the effectiveness of the drug Ferrous sulfate 325mg for hypoxia?

Research shows that iron supplementation can influence oxygen sensing pathways and may help reduce symptoms related to hypoxia, such as those experienced in high-altitude environments. However, in a study with rats, ferrous sulfate was found to aggravate certain hypoxia-induced conditions, suggesting that its effectiveness may vary depending on the context. ^{1 2 3 4 5}

Is ferrous sulfate 325mg generally safe for humans?

Ferrous sulfate, a common iron supplement, can cause side effects like stomach upset and diarrhea, and may pose risks for young children with malaria. Excessive iron intake in infants and young children can lead to growth issues and organ damage. ^{1 6 7 8 9}

How does the drug ferrous sulfate 325mg differ from other treatments for hypoxia?

Ferrous sulfate 325mg is unique because it provides a high dose of elemental iron, which can help increase hemoglobin levels, potentially improving oxygen transport in the body. Unlike other forms of iron supplements, ferrous sulfate is known to result in a substantial increase of non-transferrin-bound iron, which may pose safety concerns but also indicates its potency in iron delivery. ^{6 9 10 11 12}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effects of modest iron loading on iron indices in healthy individuals. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Effect of iron supplementation on the expression of hypoxia-inducible factor and antioxidant status in rats exposed to high-altitude hypoxia environment. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Intravenous iron supplementation may protect against acute mountain sickness: a randomized, double-blinded, placebo-controlled trial. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Ferric carboxymaltose improves exercise capacity and quality of life in patients with pulmonary arterial hypertension and iron deficiency: a pilot study. [2020]

6. United States 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. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of two doses of elemental iron in the treatment of latent iron deficiency: efficacy, side effects and blinding capabilities. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Trace Element Interactions, Inflammatory Signaling, and Male Sex Implicated in Reduced Growth Following Excess Oral Iron Supplementation in Pre-Weanling Rats. [2022]

9. United States 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. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Anemia of pregnancy: evaluation of the effectiveness of routine dietary supplementation program in an Israeli community. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Oral iron supplementation leads to oxidative imbalance in anemic women: a prospective study. [2013]

12. England 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. [2020]