EPO

If you are a fan of the Tour de France bicycle race, you know all about EPO, or erythropoietin.

EPO is naturally found in the body and its normal function is to induce the production of red blood cells, or erythrocytes. Since the red blood cells carry oxygen, more red blood cells mean more oxygen available to the muscle, which in turn means improved athletic performance.

As a drug, EPO is used to treat conditions like anemia, but it can also be used (illegally) to boost an athlete’s red blood cell count. The Tour de France is a grueling race, and many are tempted to make it a little easier. If you are caught using EPO, you are kicked out. EPO is part of a long history of doping in the Tour, and cycling in general.

The body can make more EPO naturally, under conditions of low oxygen, or hypoxia. That’s why people living at high altitudes, where there is less oxygen, have more red blood cells. It's also why Tour de France competitors often train at high altitude.

Proteins in the lungs called hypoxia-inducible transcription factors (HIFs) sense the low oxygen and induce the production of more EPO to make more red blood cells. HIFs are also present in the skin of frogs. Since amphibians can breathe through their skin, this makes sense. What is surprising is that these people found HIFs in mouse skin, too.

They wanted to see if skin HIFs had any functional significance in mice, so they rigged up chambers in which they could control the oxygen content of the air the mice breathe independently of the air that contacts their skin. They found that low oxygen levels at the skin increased EPO, but not in mice in which HIF expression in the skin was knocked out. That means that HIFs in the skin are involved in hypoxia-induced EPO production.

Part of the skin’s response to low oxygen includes increased blood flow. When they applied nitroglycerine patches (which increase blood flow) to the skin of mice, EPO levels also increased.

Another substance that increases blood flow in the skin is mustard oil (allyl isothiocyanate). This also increased EPO in mice. The authors note that it is common practice in Pakistan and Nepal to massage the skin of newborns with mustard oil and they speculate that this practice might increase the production of EPO and thus red blood cells in the babies. (Here’s the paper.)

So the next time you smell mustard oil at the Tour de France, you will know why.