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Cardiovascular Disease: A Surprising Manifestation of RED-S

If you’ve made your way through the video series on relative energy deficiency in sport (RED-S), you might be confused: How can a syndrome caused by an athlete not eating enough lead to cardiovascular disease? Isn’t cardiovascular disease of the inactive with poor diets?

You might imagine the typical person who suffers from cardiovascular disease (e.g., a heart attack or other blockages of blood vessels) is a middle-aged, sedentary (i.e., non-exercising), overweight male who eats a diet high in saturated and trans fats. This person looks very different from the over-exercising and under-fueling athlete you might picture with RED-S. Furthermore, exercise is widely touted to reduce the chances of cardiovascular disease. However, the International Olympic Committee (IOC) consensus statement on relative energy deficiency in sport (RED-S) claims that cardiovascular disease, including atherosclerosis, which is buildup of plaque on the walls of blood vessels that can lead to heart attack, can be a manifestation of RED-S. What gives?

Well, we aren’t entirely sure how RED-S might cause cardiovascular disease (or to be honest if it causes cardiovascular disease), but we do have some strong evidence showing that early cardiovascular disease occurs more often in athletes with RED-S than in athletes without RED-S, particularly when RED-S manifests as menstrual dysfunction.

Let’s dive into the data:

  • This study collected data and results from studies performed over several decades and synthesized them. Overall, it found that low estrogen levels and functional hypothalamic amenorrhea, or absent menstrual periods due to low energy availability, are associated with early atherosclerosis (plaque build up in blood vessels)

  • This study looked at athletes with menstrual dysfunction (i.e., amenorrhea or oligomenorrhea) and compared them to athletes without menstrual dysfunction and non-athletes. It compared the ability of the athletes’ brachial arteries to dilate, which was an indication of the health of the vessel and a proxy for the health of all of their blood vessels. Healthier vessels dilate more when stimulated. The brachial arteries of the athletes with menstrual dysfunction did not dilate as well as the brachial arteries of athletes without menstrual dysfunction. Additionally, the athletes with menstrual dysfunction had blood tests that showed worse lipid profiles, meaning measurements like bad cholesterol (i.e., LDL) were higher, than in athletes without menstrual dysfunction

  • This study was performed among dancers and had similar findings as the one above. Reduced dilation of the brachial artery was correlated with reduced bone density, menstrual dysfunction, and low serum estrogen, which are the elements of the female athlete triad

If you want to get into the nitty-gritty, below are some hypotheses about how this correlation might actually be causation. Most of them relate to estrogen-deficient states, which can result from RED-S.

  • Nitric oxide (NO) is a molecule produced in the body that is responsible for many normal functions, including blood vessel health, blood vessel dilation, and prevention of platelet aggregation (an important step in the cascade that leads to heart attacks and other blood vessel blockages). Estrogen plays a role in the generation of NO, so NO can be reduced in estrogen-deficient states like RED-S and athletic menstrual dysfunction

    • Interestingly, exercise normally promotes NO synthesis, but this relationship is attenuated when estrogen is low. Estrogen appears to act as a gatekeeper of this relationship

  • Estrogen likely plays a role in preventing vascular inflammation, so vascular inflammation is enhanced in estrogen-deficient states and can lead to cardiovascular disease

  • Estrogen increases the liver’s uptake and removal of bad cholesterol (i.e., LDL), and bad cholesterol is a risk factor for cardiovascular disease

  • Estrogen deficiency and increased LDL can combine to wreak havoc on the lining of blood vessels over time. As above, estrogen leads to less NO synthesis, which when combined with increased free radical formation (which can occur after exercise due to increased oxygen usage by the body) can lead to increased oxidation (a chemical reaction adding an oxygen atom and removing electrons from a molecule, often making it more unstable) of the LDL (and remember this LDL is at high levels in estrogen-deficient states!). The oxidation of LDL is an important step in the progression of atherosclerosis

On the left, you see a constricted vessel. On the right, you see a dilated vessel. NO works to dilate vessels, which allows greater blood delivery.Source: Wikipedia Vasodilation.

If you take nothing else from this recap, please know that menstrual dysfunction that results from RED-S can cause cardiovascular disease. Further, it can prevent the beneficial effects of exercise that normally prevent cardiovascular disease. Finally, and most importantly, recovery of a normal menstrual cycle shows a return in vessel dilation, likely representing a return to cardiovascular health. Let’s get out of the RED-S!

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