Iron status and human metabolism
Research type
Research Study
Full title
Effects of endogenous iron status and intravenous iron on human skeletal muscle metabolism at rest and during exercise
IRAS ID
122938
Contact name
Matthew C Frise
Contact email
Sponsor organisation
University of Oxford
Research summary
Research Summary
Why are we doing this study and what is its purpose?
We know that iron is essential for human cells to sense and respond to oxygen levels. Our group has shown that artificially low iron levels cause exaggerated responses to low oxygen, and that giving iron to healthy volunteers reduces responses to the same levels of oxygen. We now want to find out how differences in iron levels affect muscle function, partly because it has recently been shown that people with disorders affecting oxygen sensing have abnormal metabolism.
This study will answer the question of the extent to which human muscle metabolism and exercise physiology are affected by iron levels. The purpose of this study is not to test the safety or effectiveness of intravenous iron since this is already known. We hope this work will help us to understand better the consequences of iron deficiency, which is extremely common, and also one day develop new treatments for conditions affecting muscle metabolism.
Who will be taking part?
We need 32 healthy volunteers, half with iron deficiency, to complete the study. Participants will be aged 18 or older, in generally good health and able to exercise on a fixed bicycle and go into an MRI scanner.
Where will the study happen?
The study will take place in University of Oxford research facilities.
What is involved?
Participants will have a special scan of a calf muscle at rest and during exercise and then have a bicycle exercise test. They will do this on two mornings up to a week apart. After the first morning they will have an infusion of iron or placebo. We will also be asking them to complete assessments of fatigue and concentration, which have been linked to iron levels.
The NIHR Oxford Biomedical Research Centre is funding the study.
Summary of Results
: Iron deficiency has long been known adversely to affect peoples’ ability to exercise. It also seems to be particularly bad for people with heart and lung diseases. This is not just because iron deficiency can cause anaemia – other processes seem to be at play.
Previous studies in animals suggested that iron deficiency directly affects the way the body uses carbohydrate as a fuel for exercise, and also impairs the way mitochondria (a part of the cell important for energy production) work in muscles. However, how important these effects are for humans was unclear from these studies.
In this study we used two main techniques. First, whole-body exercise testing on a static bicycle at increasing workloads to see how well the body worked as a whole. Second, we used MRS (magnetic resonance spectroscopy) scans of exercising leg muscles to determine how well the mitochondria were working. We did this in healthy people with and without spontaneously occurring iron deficiency, for example due to blood donation or heavy periods. We then gave half the participants an infusion of intravenous iron and repeated the tests about one week later, to see what was the effect of correcting the iron deficiency.
Combining the results of these two tests suggested no significant effect on the way in which the mitochondria worked, but that iron deficiency made the body as a whole behave as if there was a shortage of oxygen. The evidence for the latter effect was an abnormal level of lactic acid in the blood during exercise in people with iron deficiency, which went back to normal after intravenous iron was given.
The study helps us to understand how iron deficiency damages human health, particularly in people with heart and lung diseases, where there may already be problems delivering oxygen to the tissues. It also helps us better to understand how we might use intravenous iron as a treatment for some common medical conditions.
REC name
South Central - Oxford B Research Ethics Committee
REC reference
13/SC/0439
Date of REC Opinion
17 Oct 2013
REC opinion
Further Information Favourable Opinion