Iron Metabolism Interactions With Energy and Carbohydrate Availability

Written by Ben Bunting: BA(Hons), PGCert. Sport & Exercise Nutrition. British Army Physical Training Instructor.  


Iron metabolism is essential to the production of energy and carbohydrate, which are required for the maintenance of an active body.

However, the ability of the body to metabolize these two nutrients depends on a variety of factors, including how quickly the cells use and release these compounds, and how much of each they have available.

There are several mechanisms by which the body can metabolize iron, and researchers have found that there are a number of interactions between these processes.

Non-heme iron absorbtion

Iron is one of the most essential elements in all living organisms. It is required for oxidative synthesis of ATP.

It is also important for many metabolic reactions. Although it is a vital nutrient, it can be harmful when taken in excess. Hence, it is important to control the amount of iron that is absorbed in the body.

This review paper reviews the factors that influence iron absorption. It highlights gaps in our knowledge and suggests nutritional recommendations for athletes.

Heme is a complex of proteins which is important in many biological processes. It is a component of hemoglobin.

Heme can be found in a variety of cell types, including erythroblasts and macrophages. During phagocytosis of erythrocytes, most of the iron is recycled by macrophages.

This process is controlled by hepcidin, which regulates transferrin.

Hepcidin is produced by the liver and its concentration is decreased in individuals who are anemic or have low iron stores.

Consequently, they have lower hepcidin concentrations and therefore, lower hepcidin-ferroportin interactions, which decrease iron absorption by enterocytes. Several transcription factors are involved in this process.

However, the precise role of hepcidin in regulating iron homeostasis remains unclear.

An important factor influencing non-heme iron absorption is the presence of phenolic compounds.

A recent study found that regular consumption of tea inhibited the accumulation of storage iron in genetic haemochromatosis patients.

The study showed that the tea drinking group reduced storage iron by a third, compared to the control group. The results revealed that phenolic compounds inhibited both heme and non-heme iron absorption.

In the present study, the heme-Bach2 axis was examined in vitro in normal Apc-deficient cell lines.

The Bach2 protein is important for regulatory T cell differentiation, and the heme-Bach2 axial complex may be involved in the signaling cascade.

These results demonstrate the importance of the heme-Bach2 interacting to regulate immune response.

In an exercise scenario where muscle glycogen is depleted by 50 percent, the availability of muscle glycogen is likely to upregulate cell signaling and gene expression.

This could lead to reduced energy availability and possibly exacerbation of inflammation. This has important implications for sports performance.

Another syndromic form involves an overactive IRP1 that prevents the formation of heme. An overactive IRP1 has been shown to prevent the translation of ALAS2, resulting in low heme.

Similarly, in X-linked ABCB7 deficiency, the export of Fe/S clusters from cells to the cytosol is reduced.

The heme-Bach2 axis is also important for the somatic hypermutation of immunoglobulin genes. It is also necessary for the regulatory T cell differentiation.

There are a number of dietary sources of non-heme iron in the western diet. Fortified grains are a major source of this iron.

These supplements are intended to be used as a preventative measure against iron deficiency anemia.

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Transferrin saturation

The interaction between iron metabolism and carbohydrate and energy availability is an important consideration for human health.

This is because excess iron can lead to cardiomyopathy, bacterial infection, and other adverse health effects. Therefore, it is recommended to avoid excess iron intake.

Iron is a mineral that is essential to the human body. It is necessary for growth, reproduction, and the repair of cells.

In addition, it supports the transport of oxygen. It also plays a critical role in cell growth and DNA synthesis. It is a component of hundreds of proteins in the body.

The balance between iron levels requires tight regulation at both the tissue and cellular level. This is achieved by a number of proteins that regulate mRNA stability, synthesis of iron-using proteins, and translation.

In particular, the hepcidin hormone is known to regulate the amount of iron stored in the body. Hepcidin expression is increased during inflammation and endoplasmic reticulum stress.

The liver is the primary site for synthesis of hepcidin. In addition, hepcidin inhibits the recycling of iron from the gut. This decreases the amount of available iron, which can lead to an increase in iron deficiency.

Hepcidin also has an antimicrobial role, by limiting the availability of iron to microorganisms. Hepcidin can be internalized by macrophages. It can be recycled back into the gut or exported to spleen to aid in the recovery of heme.

Regulatory proteins can bind to the iron-responsive elements (IREs) that code for key proteins involved in iron metabolism.

The binding of IRPs to IREs results in the inhibition of mRNA translation and protein synthesis. It also reduces the ability of heme synthesis in immature red blood cells. These enzymes are required for the production of hemoglobin and the repair of damaged cells.

They are also important in the immune system. In some cases, mutations in hepcidin cause abnormal accumulation of iron in the tissues.

Although the precise mechanisms by which hepcidin regulates iron absorption are not fully understood, hepcidin may play a significant role in the innate immune response.

Hepcidin is upregulated during inflammation and hypoxia, and hepcidin mutations can cause abnormal accumulation of iron in the tissues. In adolescent girls, the RDA of iron is 15 mg per day.

Hepcidin increases for about three to six hours following exercise. This increase is likely due to a response to exercise-induced inflammatory responses, including a boost in interleukin-6.

However, most studies fail to adjust for the confounding effect of inflammation. Nevertheless, exercise-induced hepcidin increases have been found to result in decreased iron uptake.

A recent study in the European Prospective Investigation into Cancer and Nutrition (EPIC) has suggested that red meat may be associated with an increased risk of esophageal adenocarcinoma.

Similarly, a systematic review of 17 prospective cohort studies with 156,427 participants suggests that serum iron is inversely associated with the risk of coronary heart disease.

Limitations of field-based research with elite athletes

One of the key systems of interest for athletes is iron metabolism. Athletes who suffer from anemia, for instance, can benefit from nutritional advice, especially if they're looking to compete at the highest levels.

Until now, we've had little to no direct evidence of the effects of exercise on iron-regulatory responses. However, a recent study conducted in the UK suggests that the heat might be a detriment to the absorption of ferritin, especially in men.

So what does a high-performance athlete do to keep their iron levels on point?

The answer is a multi-pronged approach that includes a flurry of dietary interventions.

In the end, this study was able to determine that a well-formulated omnivorous diet was the best choice for improving CHO availability, and may well be a worthy candidate for an athletic training program.

This isn't to say that other approaches are not viable, of course. In fact, we found that the best choice for most of our athletes entailed a multi-pronged, multi-component approach, in which the most important component was a CHO-rich diet, supplemented by a flurry of supplemental dietary components.

Among other things, we sought to determine whether a high-performance omnivorous dietary approach is the best choice for improving CHO availability, while at the same time identifying which components may be most important in ensuring the best possible outcome.

In one study, 20 international level male race walkers were recruited and randomly assigned them to either a high-performance omnivorous diet or a flurry of supplemental CHO-rich dietary components.

Of the 18 participants, one completed both camps. The other 17 were excluded, including two athletes with an unusually high level of iron stores. The rest of the samples were screened for other factors, but all were deemed to be fit, healthy and well-motivated individuals.

Despite their varied training backgrounds, all were able to provide informed consent. The study was approved by the ethics committee at the Australian Institute of Sport.

Despite the obvious challenge of recruiting and retaining the best of the best, the results were well worth the effort.

The key to success is to make sure that the right components are available at the right times.

For example, a flurry of supplemental choline enriched CHO-rich dietary components was a better choice for a high-performance omnivorous athlete than a high-protein, high-carbohydrate approach.


Iron metabolism is influenced by the availability of energy and carbohydrate. In addition, the presence of inflammatory conditions, such as rheumatoid arthritis, autoimmune diseases, and cancer, can reduce the amount of circulating iron.

The presence of iron in the cytosol induces the binding of iron regulatory proteins (IRPs) to iron-responsive elements (IREs) in messenger RNAs.

IRPs are involved in regulating the synthesis of key regulatory enzymes that control cellular iron concentrations. IRPs also affect the synthesis of proteins involved in iron use and storage.

Moreover, binding of IRPs to IREs inhibits the translation of these key regulatory enzymes. This inhibits protein synthesis and cellular iron uptake. It is believed that this physiologic reaction is responsible for the development of anemia.

Athletes and pregnant women are at a greater risk for anemia. In addition, anemia is associated with an increased risk for cardiovascular disease, cancer, and infection.

During endurance training, the availability of carbohydrates may influence iron metabolism. Studies have shown that CHO intake during intensive training increases muscle glycogen content.

However, the exact impact of CHO intake on iron metabolism is still unclear. A future study is necessary to determine the effects of CHO intake on iron metabolism.

It is believed that hepcidin levels in the blood increase during inflammation. In addition, hepcidin serves as a protective mechanism against the growth of pathogenic microorganisms.

Hepcidin also regulates the iron homeostasis through action of gluconeogenic signals. It also supports gluconeogenesis in the liver during energy restriction.

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