The Speed Gene

Hi and welcome to Genetics Decoded. I'm Sharon Palmer, your host. Please note that the information presented here today is not to be taken as medical advice. If you like the podcast, please go in and like and subscribe.

We are going to talk about exercise. So, whether you're a gym junkie or a couch potato, there is really important information here. We can start to use our genetics to make much better decisions around our exercise, get much better outcomes, and limit our negative outcomes, such as injury, and risk of injury. We are going to look at a particular gene. It's called Alpha-actinin-3. You all have that gene, but it won't be working the same way across the board for all of you. Find out how to take this information and make better decisions around your exercise.

Today, we're going to be looking at exercise, which might be really timely because, as I am recording this, the Paris Summer Olympics are just about getting ready to start. And when we look at exercise, we know that genetics is playing a really, really important role in performance and outcomes. When you're looking at these Olympic athletes, you are really looking at the real extremes of genetics: the people that are really strong and powerful, and the people that are the long-distance runners. When you go and watch some of this, look at the people who are the sprinters. So the 100m men, they have a certain look, right? They are strong, they've got very well-defined muscles, and boy, are they quick. Compare that to what a marathon runner looks like. This is what we call phenotype. Phenotype is not just a function of training. It really is a function of genetics impacting on our phenotype. And it wouldn't matter how much training you gave that marathon runner, you would never make them an Olympic sprinter, and vice versa. It's not a function of training. We've got, we've got muscles, we've got certain properties that they can do and not do, and your genetics is playing a role. And that's what we're going to look at today.

There's a particular gene called ACTN3, Alpha-actinin-3, and it's a protein that is made directly within the muscle fiber itself. Now, all of you out there are going to fall into a couple of categories. There's some of you who are the couch potatoes who just go, "I don't do it. I hate it." Or "I want to do it, and I just can't seem to get up off the couch and do it, and I'm feeling guilty about it." And then you've got the other extreme. You've got these people who are doing an enormous amount of exercise. They might be competitive. And then you've got most of the people in between.

If any of you fall into that first category, if you're somebody who's not regularly exercising, the first thing I'm going to do is really encourage you to do something, not to guilt you into it and make you feel bad. But sometimes, when we're not doing something, it seems very difficult to kind of get to the point where we start. And often, with exercise, we make it so complicated. It's like, "Oh, should I do this? And I do that?" And all these podcasters are talking about these strength training regimes, and someone else is talking about the marathons that they that they run. And you look and you go, "Oh God, that seems like so much effort. I can't do that." And you stay in this point of inertia. But the thing to know is that when we look at the benefits of exercise, the people who get the greatest benefit are the people who go from doing nothing to doing something. So if you fall into the category of not exercising, just do something. Even if it's just getting up and going for a walk. Don't complicate it. Don't make it too hard. Make a start, and you can figure out how you're going to continue with that down the track.

We also know that your muscle-to-fat ratio is one of your most important biomarkers of aging. And as we age, we want to hold on to muscle. We want to try and stay in this anabolic state, which is the state of building. And we see from the research that, you know, sometimes men in their 70s, at around about the age of 75, we see this massive loss of muscle. And at the same time, we see this increased incidence of disease. It is so important to hold on to your muscle mass. And if you're not exercising, you are really at risk of not having enough.

What is your current belief system around exercise? Do you fall into this category of going, "No pain, no gain"? And I still see that a lot at gyms. I see, I see a lot of that around personal trainers, like, "We just need to work really, really hard. And if it hurts, it's good. You're going to get good outcomes." And that, you know, if you train hard, you will get the results that you want. What we know is that's not true. Is that, you know, just because you're working really, really hard does not mean that you're going to get the outcomes that you're looking for. We know genetics is playing a role in 66% of athletic performance. And if you go into the gym, I could get a hundred people. I could kind of keep their diet pretty similar. We could put them into the gym, and we could get those 100 people to do exactly the same thing. And it wouldn't matter whether it was a weight resistance program or maybe it was a cardio-based program. If we tracked those people over the course of a few months and they did exactly the same thing, they would not end up with exactly the same results. And that's because our genetics is playing a role in how we're responding to that training. You would see, if you assess those people, some people would get great outcomes, other people would get quite negative outcomes, and they're the people in between that, you know, maybe not too much, um, you know, pro or con at all.

If we're exercising, we're usually doing it for a reason, especially if you don't like it. You want to make sure that it's delivering you some outcome. But how do you guarantee those outcomes if it's not just a function of getting in and going hard? How are you going to modify your training, what you do, how frequently you do it, in order to give you the outcomes that you want, and to at the same time minimize the negative outcomes, like things like injuries or muscle soreness? I see people at a clinic level. You know, sometimes we think of muscle injury and we think, "Oh, we've just strained it a little bit, and in a week or two, it'll be fine." I see people who have got really severe injuries, and they can be sidelined for weeks or months. And that's, that's not good from a health point of view. If you're not able to exercise at all, you very rapidly begin to lose that muscle, which is is not a good thing.

Many of you may be playing team sports. Or if you're not playing it now, if you look back to your childhood, most of us were either playing football or netball. There was some kind of team sport. And even now, even if you look at professional teams, the training is usually very similar across the board. We show up at the same number of times for training, so maybe we're training two or three times a week. If you're a professional athlete, more frequently. We're there for the same amount of time. We have the same rest and recovery. What we're seeing from sport genetics is that no one on a team, that whole team, should not be trained in exactly the same way. As we start to integrate genetics into sports, and particularly into professional sports, you're going to see a real stratification of how people train. There will be people who will be training more frequently and more intensely. There will be other team members that will have much longer rest and recovery times. They may not do anywhere near the same types of weights or the heaviness of weights. Because what we know is, if you train within your phenotype, you will get much, much better outcomes. If you train outside of your exercise phenotype, not only do you not get the gains you're looking for, you will often end up with these negative outcomes. It's really good to start using your genetics to go, "If I'm going to go into the gym, if I'm going to do something, let me maximize my results."

If we look at sports genetics on a broad level, we've had a really good look at sports genetics over the last 20 or so years, and the research is really exponential. We're learning so much more as each year goes by. There have been about 120 genes that have been tied into exercise performance. And this is what you will see. The future of sports will be: you'll start doing your genetic genotyping, and your trainer is going to come in, and they're going to develop your training program, your recovery program, and your sports nutrition, and it will all be based on your genetics. And you don't have to be a professional athlete to engage in those things. Genetic screening is really widely available now. It is possible to go in and look at a whole range of genes that impact on that and modify what you're doing, even if it's going down to the local gym, is modifying what you're doing so that you can end up with some better outcomes as well.

The focus of the podcast today is to not look at all the genes, but to look at this one particular gene called Alpha-actinin-3. And it's going to play a major role around a lot of key areas around sports performance. The levels of this protein, this Alpha-actinin-3 protein, in your muscle is going to really impact on your muscle strength, so power and strength. It is going to impact on your speed. In fact, this ACTN3 gene is usually referred to as the speed gene. And we see again, if we go in and look at these Olympic sprinters, Olympic sprinters without fail fall into a particular genotype. If you do not have really good levels of this Alpha-actinin-3, you will not be competitive at an Olympic level. So this is how much it impacts. Because this protein is changing how quickly the muscle can contract. If you're a sprinter, that muscle fiber has to contract very, very rapidly. If you don't have that protein sitting in there, the muscle simply cannot contract quickly enough for you to be able to be competitive in that sprint event.

We also know that this protein impacts on muscle size, like how big can the muscle get. And it's not a function of just training. In some people, the muscle responds very, very quickly to weight and resistance work. And in other people, it responds really, really poorly. These are the people that are in the gym that are lifting weights, they're doing all these things, they're going, "Why are my muscles not getting any bigger?" You know, "I must need to go heavier," or maybe, "I need to start taking steroids because nothing else is working." Looking at what might sit behind that, it's not just a function of poor training or not enough training.

We also know that this protein is changing the way the muscle produces energy. So much of what we're capable of doing at a sporting or an exercise level has to do with how the muscle makes energy. Can you produce that energy really, really quickly? And this is where you get that power and speed. Or are you on the opposite, where it takes your muscle, doesn't produce quick energy? In fact, it might take five to six minutes to really kick into energy production. But once it started to make energy, it is so incredibly efficient. And this is where we see stamina and endurance. And have a think about that. If you're a sprinter, you need to make energy within fractions of a second. It doesn't even take a second. This ATP energy is produced in fractions of a second. That 100-meter race is over in 9 to 10 seconds. Now, if you have the complete opposite phenotype, in which it's taking your muscle about six minutes to get into energy production, the race is well and truly over before your muscle is even ready to go. And this is why it is so difficult to take someone with that phenotype. No amount of training is going to make them into this great sprinter. It's just not going to happen. Their muscle just does not have the capacity.

If this Alpha-actinin-3 is so important around how our muscle works and how we exercise, the question is, well, how do we know how much of this protein we're making in the muscle? Do I fall into the category where I've got a lot of it, or do I make an intermediate amount, or do I make very little of it? And again, it comes back to your genetics. Your gene, and your genotype in that gene, is going to tell us exactly what category you are.

If we look at these three genotypes, there is what we call the RR genotype. These are the people that make very good quantities of this Alpha-actinin-3. The intermediate genotype is called RX. Now, these people still make this Alpha-actinin-3 protein, but they make it at reduced levels. And then finally, we have what's called the XX genotype. Not only do you, if you fall into this genotype, it's not that you produce reduced levels, you produce absolutely none. There's none. And it's not a rare genotype. There's probably about a billion people worldwide that fall into this XX category. And by knowing your category, you're going to know how much of this protein am I making? How is that going to change how my muscle works? And what am I going to ask it to do?

Whenever we look at genetics, there's usually a reason that a gene mutates. Why would it be that some people have really good levels of this protein, and other people have absolutely none? And it has nothing to do with making us great athletes or making some of us really good sprinters and others really suited to endurance. That is really just a consequence of what's happened here. If we look at this gene, we can trace it back that the change started to happen about 40,000 to 60,000 years ago. So if we look at human history, we know that we all kind of started in Africa. And if we look at the percentage of the population, the African population that has the normal presentation of this enzyme, these are the people that make really good levels of the protein. The majority of that African population have this, what we call RR genotype. They make really good levels, and they're fast, and they're powerful, and they're quick.

Now, when we started to migrate, so as the human species started to migrate, they went out of Africa and they started to head up into the northern hemisphere. But when they started to head north, their environment changed. So it started to get colder. The food supply was not as reliable. You can see in winter, very few things grow. So there was a real problem with getting enough food and enough energy in order to be able to migrate and to survive in this colder environment with a not reliable food supply. The muscle, the way the muscle produced and used energy, began to shift. It started to move into a form of energy metabolism that was just simply more efficient. So it produced more energy, and it could produce it over a much longer and sustained period of time. And it's really interesting. If you look at genetics and you kind of trace the evolution of this mutation, is that, you know, you see the people here in Africa who have got the really good levels of this protein. And then we start to see there were more people that started to have the single genetic mutation, starting to get a little bit better at producing energy. And then as we get right up into the northern hemispheres, you saw the people that started to get the double mutation. This is the XX genotype. They're in much more extreme conditions. Becoming more energy efficient helped with survival. So this is where we passed this genetic mutation on. The consequence around our sports performance is just a function of change. And it's one of those things where it comes back to: you just can't have everything. So you can't have speed and power, and you can't have endurance. You almost have one or the other. But it really was more around survival than it was to do anything with how our muscles performed.

How can we take this information around Alpha-actinin-3 and use it to change how we're going to train in the gym, particularly as we look at strength and resistance training? I have seen a real shift in the messaging that's coming out around exercise. For the longest time, I think there was this real focus on cardio fitness. We saw the 70s and people were just runners, run, run, run, run. There has been a real shift in that messaging to looking at being strong, making sure we've got muscle. We're saying to women, "Forget about looking at your weight. Forget about being skinny and get strong." And people hear this messaging and they think, "Okay, I've got to start to do some weight and resistance work." So whether you're going off into the gym, or whether you've got something at home, maybe you've got some resistance bands, you begin to go in and you start to train. But I want you to think about the way that you train. The way that you engage with this resistance work should be different based on this exercise phenotype.

If we look at the people, these are the people, these RR genotypes, that make really good levels of this protein. When they go in the gym, these are the people that look at a weight and grow muscles. That's how responsive they are. The minute they start to do some weight or resistance work, it's almost like their muscles just grow overnight. They get a very quick and a very good response, and they're usually happy about that. "I go in, I put this effort in, and I get this really good outcome." The people who are in between, which are the RX genotype, they're making slightly less of this Alpha-actinin-3. The slightly less production of this protein doesn't impact too much around strength. Their strength is not to the same degree, but they're not compromised. So again, if they go into the gym and they do some weight and resistance work, they have a really good response. The people who fit into those two categories, when we're looking at what they should be doing from a weight and resistance point of view, they can be lifting heavy. They don't want to be doing a lot of repetitions. You'd want to be sitting at a maximum of around eight reps. And when you can comfortably do those eight reps, you would start to take your weight up. The people who are making really good levels of that protein, the RR genotype, these are the people that can do what we call maximal weight reps. People go, "Just do one rep, but go as heavy as you possibly can." The RR genotype is really good at doing that. The people who are making less, so sitting in the middle, you'd want to be cautious about doing those maximal weight reps. Probably better to stay away from them, especially if you're fatigued or you're not very fit. So just be careful. You, as the middle genotype, don't want to take your weights and your weight training to the absolute extreme.

Then we've got the XX genotype. So these are the people who are making none of this protein. And that will profoundly change what they do in the gym and how they do it. They go about it. Probably at a clinic level, the people who I have the most resistance with in handing off this information is if I have to tell a man that he has this XX genotype and he makes none of this protein, and getting into the gym is not going to deliver them, deliver the results that he wants. And in fact, he should stop trying to lift these very heavy weights and focus more on lowering his weights and doing higher reps. These are the people that want to do repetitions around about 15. Women go, "Fine, I can do that." But I see a lot of resistance in men. But if you start to ask your muscle to do something that it's not equipped for, remember, there's just none of this protein. It's the muscle just doesn't have that ability to contract and handle that type of weight. And if you force it to do so, this is where you will end up with a lot of injuries as well.

If you fall into that XX category, where you do not make this protein, you are at risk of something called sarcopenia. So sarcopenia is an increased rate of muscle loss as we begin to age. So these people, these XX genotypes, are really at risk of losing muscle. It is really important for them to get into the gym or do some kind of weight or resistance training, but to do it around high repetitions and low, and low weights. So the way that we train should really vary depending on our genotype here.

One of the things that happens when we exercise is we break down that muscle. We break it down into its component amino acids. That happens for all of us. We don't want to lose, we don't want to lose these amino acids through that process. Your body has a number of enzymes that will help to reconstitute those amino acids and take them back and turn them back into muscle. And this is kind of the way in which the muscle grows. We exercise it, it breaks down, we reconstitute it. But our ability, how much of that muscle we break down in the first place, is again dependent on whether we have this Alpha-actinin-3 protein in the muscle.

So if we look at a muscle, and we've got to come down to the level of the muscle fiber, this Alpha-actinin-3 protein sits right within the muscle fiber itself. And it's playing a very big role in how the muscle begins to contract. Now, when the muscle contracts, it's very important for the muscle to have stability. And this is what this Alpha-actinin-3 protein does. It gives the muscle a lot of stability upon contraction, which means that you're going to break down less muscle. In the people where they don't have any of this protein, as the muscle contracts, it leads to a lot more muscle breakdown. And they're really at risk of losing a lot of muscle through the process of exercising.

And I don't know if any of you have heard, there's something called exercise-induced rhabdomyolysis. If you've ever been watching, you know, those long-distance events, those marathon runners, you see the people who get to the end and literally almost collapse. Some people die through these, through these doing marathons or doing ultramarathons. A lot of that is because of this exercise-induced rhabdomyolysis. It is life-threatening. If you're breaking down a lot of that muscle, it is just, just, and you can't reconstitute it, it is just dumped into the bloodstream. It goes off to the kidneys and it can shut down your kidney function. This is where we see why it can be fatal. And people who are the XX genotypes, the people not making any of this Alpha-actinin-3, they are very, very prone to exercise-induced rhabdomyolysis. In fact, when these classes like F45 and Cardio Fit were released in the US, the rates of people hospitalized because of exercise-induced rhabdomyolysis were increased. Again, you think, "Oh, that's just some weird thing that's hardly ever going to happen." But I've had a lot of patients who have had that genotype. And I remember recently talking to a man who had it, and I told him he was really vulnerable to this exercise-induced rhabdomyolysis. And he goes, "Wow, that's really interesting." He said, "I've been hospitalized twice for that." Not through exercising, but his job was very physical, and it was outside. And there were a couple of times, just through doing his job, that he ended up breaking down too much muscle. And especially if you're training in heat, then this process can really increase.

For those people with the XX genotype, they want to be very careful about making sure they're very well hydrated before they exercise, during, and afterwards. And if you're ever doing these like intense exercise sessions, or you're doing these long exercise sessions, if your urine becomes really dark and really brown, that's often a sign, the beginning signs of rhabdomyolysis. But I have, I've seen people hospitalized. Remember, one woman said it was touch and go for her. Don't just think that it's nothing that will ever happen. But there are some people who are very unlikely to get exercise-induced rhabdomyolysis, and other people who are really at risk as well. And that means too, how intensely you train is really important. The more intense your training is, the longer you train for, the greater the breakdown.

It is possible to track some of these breakdown products in blood testing. So a lot of athletes will look at things like lactate dehydrogenase. They will track things like creatinine kinase. They will look at things like A.L.T., which is one of your liver enzymes. And when those things, when those levels go really high, it can be a real sign that you've broken down a lot of muscle, or also that you're overtraining. And to try and keep it in perspective, the people who have the XX genotype, who make none of this protein, when they are doing these longer distance events, their production of some of these can increase by more than 5,000%. So you can just see how much muscle can be broken down. But if you're training to try and gain muscle, you don't want to be breaking it down and losing that muscle mass. So you've got to train smart through this process as well.

Now, we're going to look at this endurance versus power. And again, your Alpha-actinin-3 is going to play a very important role. In fact, if we look at the thing that makes the biggest difference, it really is around this muscle metabolism. We just talked about that evolutionary pattern. It was really the muscle changing how it made energy that was the most fundamental shift. And how much energy we can make, and how quickly we can make it, is going to have a very big bearing on what kind of sports and activities we will be good at.

If you are the RR genotype, so these are the people who are making a lot of this Alpha-actinin-3, their muscle metabolism is very unique. It's what we call this ATP energy production. It's anaerobic. This energy production happens in fractions of a second. It is not reliant on you delivering any oxygen to the muscle to have it work. In fact, what you're going to do is you're going to use your glycogen stores in the muscle to rapidly produce energy. And if you want to be fast and quick and powerful, so if you're a powerlifter, your muscle has to work really quickly. If you're a sprinter, you must have that kind of energy production. But you can't sustain that for a very long time. Look at those people who do the 100-meter race. They're flat out, and then they often collapse at the end. They're breathing really heavy. If you ask them to do that over and over again, they can't. Their muscle becomes fatigued very, very quickly. Those people can work really hard, really fast, but they fatigue quickly, and then they need time to rest and recover. So these are the people that are very good sprinters and powerlifters, anything where you need speed and power.

Then you've got the people in the middle. These are called your RX genotype, and they are really unique. They have a combination of both. And this is where they get quite a lot of flexibility as to what they are good at and what they can do. They still have this fast, instantaneous production of energy. And this is where they are still really good at sprinting. Personally, I had this really interesting event that happened for me when I was in school. Is I was a very good athlete, and I was a very good sprinter. And I was invited to train with these elite athletes. And so I showed up on my first training session, and we had to do these sprints. So it was like, "Okay, you're going to run at 25% capacity. And now you're going to take it up to 50% capacity." When we got to 50%, I was already at 100%. Like, when I look at my genotype, I sit in the middle. I've got this real capacity for speed. But when I trained with people who were the other genotype, where they're just so much faster, what I realized is there was no way I could be competitive. And I didn't go back after that. I just thought, "I know where my level is, and it's not going to be that." But this is where too, you know, looking at, you know, if you're trying to get into a certain level of professionalism from a sports point of view, you know, understanding where your limitations may be may be really, really important as well. Because it's hard to kind of push to the extremes. But the people who are sitting in the middle still have a lot of power, strength, and speed, just not to the same degree. And then they also have the ability to make energy through what we call aerobic metabolism. It starts to use oxygen. It is very, very efficient. And once it starts, it can go for a long period of time. So this is where you get the stamina and the endurance. So these people have a lot of flexibility. When I see them in clinic, I think those are the people that are really great around things like triathlons, where you know, you need to be able to produce energy over a period of time.

Then we have the XX genotypes, the people that are making none of this protein. As I'd mentioned earlier, it takes a while for their muscle to even kick into energy production, like somewhere between five to six, even ten minutes. These are the people I say, "You've got to make sure you do a really good warm-up before you go out and ask the muscle to perform. It's got to be ready to go. It's going to take time for you to get it there." But they have, again, this ability to have this aerobic metabolism. And they've also got a very good capacity to go in and mobilize fatty acids for energy production. And again, this is where you get this real endurance from as well.

Now, if you're working with someone who's an XX genotype, they can have long training sessions. You know, they could go into the gym, they could do 60-plus minutes. If they're going for bike rides or runs or swims, they are capable of doing longer training sessions. If you're the RR genotype, where you make energy really quickly and then get fatigued, these are the people I go, "Get into the gym, work hard, work fast, and then be done with it. Go home and rest." And 30 minutes is plenty for those people. And you certainly wouldn't want to be doing more than 45 minutes. And then the people in between have got a little bit more flexibility around shorter training sessions and longer training sessions. But again, there's often that belief is, "I've got to go into the gym and I've got to be there for like an hour and an hour and a half in order to get any outcome." Maybe, but it may be counterproductive to what you're trying to do as well.

Now that we've got genetic screening, it really is time to become a lot more informed about how we exercise and how to get much better outcomes. It is easy to go in and do genetic screening now. Take that information and turn it into very defined choices around what I do, how I do it, and how long I do it for. And if you get it right, you will end up with much, much better outcomes.

Thank you so much for listening to Genetics Decoded. If you enjoyed the episode, please remember to subscribe, like, and share. Tell your friends all about what we're doing because we truly are individuals. Your genetic data can be used for you to make much better decisions around your diet, supplements, and lifestyle. Join me each week to find out how.