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An analysis of the long-term effects of performance-enhancing drugs

  • By Trevor Connor
  • Published Feb. 20, 2014
The debate over the long-term effects of doping is a fierce one full of emotion. Photo: Tim De Waele | TDWsport.com

Doping vs. Muscle memory

In order for doping to get around homeostasis and have any lasting benefit, it would have to find a way to create a “memory” in our bodies. Look to our immune system for an example; we can only fall ill once from any specific virus before we generate antibodies.

And here, again, the science is mixed.

When a relatively new athlete detrains, he loses everything. But many studies have shown that when experienced, long-term athletes detrain, they lose a lot, but not all. Capillary density and VO2 max both remain above baseline. There appears to be a permanent shift in homeostatic balance.

Among strength athletes, there is something called “muscle memory.” These athletes find that if they build muscle mass and then let it atrophy, they can build it back much more rapidly, even years later.

Dr. Jo Bruusgaard and his team at the Department of Molecular Biosciences at the University of Oslo were studying muscle memory when they discovered a potentially permanent effect of testosterone doping.

Bruusgaard was studying myonuclei content, a fancy term for the number of nuclei in muscle cells. Nuclei are the protein factories of our bodies. Most cells have one nuclei, but muscle cells are huge, needing a lot of protein, so one cell can contain thousands of nuclei, according to Bruusgaard.

For a muscle cell to grow bigger and stronger, it has to first increase its myonuclei number to handle the larger protein demand — in essence, this constitutes a process called hypertrophy.

Bruusgaard studied this effect by administering a single dose of testosterone to mice. He found that the testosterone dramatically increased the effects of training on myonuclei numbers. In fact, testosterone alone had a bigger impact than training. After three months of detraining, the muscles shrunk, but the nuclei stuck around.

Bruusgaard pointed out that three months in the life of a mouse is equal to about 10 years in a human. “There is a good chance the increase in the nuclei is forever. There have been a lot of studies on the age of nuclei in humans and they seem to be as old as the humans carrying them,” he said.

The benefits of this testosterone-enhanced “muscle memory” is obvious for strength athletes, but what about for endurance athletes, for whom large muscles can be a disadvantage?

The slow-twitch fibers that we rely on actually have a naturally higher nuclei content. We need more of these little protein factories to handle all of our muscle recovery demands. According to Bruusgaard, a higher number provides a big advantage when we’re training hard and dealing with small damages in the muscles.

In his studies, testosterone had a greater impact on the myonuclei of slow-twitch muscles.

But before you go grabbing your pitchforks, remember that the most important question here is dosage. Cyclists who have doped with testosterone have done so with far lower doses than power lifters.

Testosterone was most typically used to address the fatigue at the end of three-week stage races, from Vaughters’ experience. “You’d be at a 200 to 300 range [of testosterone]. Using the patch for a short period of time would potentially increase that from 200 to 275, which is still a very low end of normal,” he said. Anything higher would immediately test positive. But he added, “This isn’t for a second, a justification to use testosterone.”

Bruusgaard reinforced this point, “In terms of cycling, I don’t know how much hypertrophy you’d want and I don’t know if these doses increase myonuclei. That is the question we are actually addressing here.” With research just beginning to ramp up, it could be years before the findings are published.

Doping vs. Genetics

Even more powerful than homeostasis, however, is our genetics. And our genetic makeup doesn’t change. Or does it?

Both Bruusgaard and Belda-Iniesta are looking at a branch of genetics called epigenetics in the fight against doping.

We’ve all seen pictures of our chromosomes as nicely organized Xs and Ys. The reality is they don’t normally fit in a cell like that. Instead, they are wound together. A better image of our genes would be a giant ball of twine (called the chromatin structure.) You might have a great gene for endurance sports, but if it’s at the middle of that ball, it doesn’t matter.

Epigenetics is the study of how our bodies rearrange that ball, turning genes on and off, to improve how we maintain homeostasis. As Belda-Iniesta describes it, our genes are like computer programs. We still get to choose which programs we install on our computer to make it work better.

“Your epigenetic changes should be maintained all the time,” Belda-Iniesta said. “The epigenetic effects should be in the program of your cells.” These epigenetic changes are sometimes long lasting; studies have shown they can be passed on to your children. More importantly, scientists are demonstrating that both training and doping can potentially alter epigenetics.

In a recent study by Dr. Jonny St-Amand and his colleagues in Canada and Japan, endurance training increased the activity of several key genes and, after 12 weeks of detraining, these genes remained highly active. This led the researchers to conclude that changes in gene expression created “memories of previous training.”

But before we get too excited and petition to ban the children of dopers for life, remember that there are few studies of the effects of doping on epigenetics, let alone the long-term effects. Just like all things in the body, epigenetic changes can be reversed. This is very new science.

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