Hyoxia Inducible Factor (HIF)

In 1968, the Summer Olympic Games were held in Mexico City at an altitude of about 2300 meters above sea level. At that time, many athletes and their coaches noticed that training in high altitude conditions was much more effective. And although the effect of such training has been known for a long time, after the games, athletes from many countries introduced regular training camps in the mountains into their routine. 

The rarefied air had a beneficial effect on their cardiovascular, respiratory and circulatory systems. While it was clear that low oxygen training was beneficial to the body, the exact mechanisms underlying this method were unknown. 

Over time, the answer was found: the basis of this phenomenon is the factor induced by hypoxia - Hypoxic inducible factor (HIF). It acts as an "oxygen sensor"; in the body, activating a wide range of processes that increase the body's performance. So it became known that HIF not only increases the number of red blood cells, and hence the performance, but also allows you to get other beneficial effects.

Discovery of the hypoxia-induced factor

Hyoxia inducible factor (HIF) was discovered by Professor Gregg Semenza of Johns Hopkins University in the early 1990s. Together with two other scientists, he received the 2019 Nobel Prize in Medicine for explaining the mechanism of action of HIF in the human body.

The significance of HIF for the human body

HIF can be thought of as an "oxygen sensor"; in the body, which works in case of a lack of oxygen in the cells. It controls one of the most important processes in the body – adaptation of cells, tissues and organs to a lack of oxygen.

The existence of HIF indicates that, contrary to popular belief, the human body is quite well prepared for a temporary lack of oxygen. 

This function is important because every cell in the body needs oxygen to generate energy. In the event of a lack of oxygen, for example, in the mountains, during physical exertion, or when the supply of oxygen to certain parts of the body is disrupted after an injury, HIF synthesis is activated. This helps to quickly restore the body's supply of sufficient oxygen for energy production and wound healing.

HIF not only ensures the adaptation of cells to a lack of oxygen, but also gives a signal for self-healing of the body.

HIF formation and its components

HIF is a small molecule protein that is constantly produced in every cell of the body. Its most abundant subunit is HIF-1α.

The HIF protein consists of two components: alpha-HIF and beta-HIF. The alpha-HIF component activates the protein: it gives a signal to start the adaptation process. With a sufficient supply of oxygen, the alpha-HIF component is degraded by the breakdown products generated during energy generation. The beta-HIF component is not destroyed, but is preserved for further use.  

When oxygen supply to cells is reduced, the accumulated alpha-HIF component can combine with the beta-HIF component. The combination of these components triggers a number of processes in the cell nucleus with the participation of genes. Professor Gregg Semenza reports direct or indirect effects of HIF on more than 1000 genes. It can be assumed that in the future the list of these genes will be replenished.

The effect of HIF on the human body

HIF has a great effect on the body. As already mentioned, it is able to activate several hundred genes. We do not aim to describe in detail every effect of HIF, but only focus on the most important ones.

The most widely known effect of HIF is the formation of erythropoietin in the kidneys and liver. Erythropoietin, often abbreviated as EPO, helps form red blood cells. 

A sheet of cells on the inner surface of veins, the endothelium, responds to HIF activation by increasing the production of vascular endothelial growth factor(VEGF). Thanks to it, the production of nitric oxide (NO) in the human body increases. Both reactions favorably affect the condition of the vessels. 

Another positive effect is increased production of the insulin-dependent glucose transport protein GLUT-4. In the long term, it reduces insulin resistance and allows you to use carbohydrates more efficiently.

Ultimately, every cell in the body responds to HIF. If the mitochondria, which are responsible for generating energy in the cell, do not receive enough oxygen to synthesize the energy source (adenosine triphosphoric acid), then their initial reaction is to change forms. In the second stage, they begin to divide in order to produce more energy more efficiently. At the same time, the process of degradation of old and damaged mitochondria begins.

HIF Negative Impact

Some types of tumors lead to localized hypoxic processes. In these cases, the effect of HIF is reversed: an increase in EPO production and an improvement in blood supply only accelerate the growth of cancer cells.

Will the effect of HIF-1α useful or harmful, depends on the dose of hypoxia. In uncontrolled hypoxia, such as localized hypoxic processes in cancer or sleep apnea, HIF becomes dangerous. It has a devastating effect on mitochondria.

However, in controlled hypoxia with adaptation to individual needs, for example, in the case of interval hypoxic training, HIF provides significant therapeutic benefits. Moreover, its action is not limited to individual organs, but extends to the entire body , which positively affects the quantity and quality of mitochondria.

Using HIF for health purposes

Changes in the functioning of the body caused by the action of HIF, as a rule, lead to an increase in working capacity. This not only helps to improve physical fitness, but also protects a healthy body from diseases and aging processes. 

If a person has health problems, the action of HIF can slow down the development of diseases or even get rid of them. For example, during hypoxic interval training, HIF can be activated without any effort, simply by inhaling air with either a reduced or a normal oxygen content. The action of HIF is comparable to the effect of sports training, but it causes much larger processes in the body.

Hypoxia inducible factor (HIF): discovery, significance, impact, and medical use.