Ergogenic Aids to Enhance Sports Performance. Podcast with Jeff Rothschild

Guest

In this episode of humanOS Radio, we welcome Jeff Rothschild back to the show. Jeff is a Registered Dietitian with a Master’s in Nutrition Science, the creator of the humanOS Fasting Program and our course on endurance training (i.e., polarized training), and a former guest on this podcast discussing the subject of breakfast skipping. Jeff is also currently conducting his PhD research under the guidance of Dr. Dan Plews (Ironman AG-World Champion) at the Sports Performance Research Institute, New Zealand (SPRINZ) in Auckland, New Zealand.

He has worked with an impressive array of athletes – his clients include multiple Olympians, State Champions, collegiate All-Americans, and professional tennis players, as well as recreational athletes and folks who are trying to complete their first triathlon. So he has plenty of expertise in sports performance and nutrition, both from accumulated experience as well as academic study.

…Especially with endurance training, but any sport, you want to think about accumulating years of training and adaptation. So, will this further the cause of the bigger picture, or will this give me a short-term benefit for maybe a long-term negative effect?

Jeff recently wrote a fascinating review exploring the impact of dietary supplements on adaptations to endurance training, which disentangles some of the complicated questions that I cited above. He came on the show to discuss his findings, and what they might mean for athletes and generally active people who want to maximize the time and effort that they dedicate to their training.

To learn more about how various nutritional supplements might affect your training – both short and long term – check out the interview below! Lastly, in the next few days, we’ll be releasing a How-Guide Guide on humanOS.me for Pro users that has specific regimens and dosing information for different ergogenic aids.

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Transcript

Jeff Rothschild - 00:00: ... Especially with endurance training, but any sport, you want to think about accumulating years of training and adaptation. So, will this further the cause of the bigger picture, or will this give me a short-term benefit for maybe a long-term negative affect?

Dan Pardi - 00:13: The market for dietary supplements to enhance sport performance has exploded in recent years. This is particularly true for elite athletes. But athletes at all different levels of sports are drawn to these products. You probably have tried some of these supplements yourself to improve your workouts. Many popular supplements, like caffeine, have been studied in the context of intermittent performance enhancement and are used with that goal in mind. But the effects of chronic supplementation, particularly in endurance training, is not as well understood. Furthermore, it is not as clear how performance enhancing supplements might influence the adaptive response to exercise training.

00:52: Training induced adaptations are the product of repeat stimuli from exercise sessions as well as accumulated changes in gene expression. Dietary intake of certain substances can, in theory, affect training adaptations. They can achieve this by increasing the exercise stimulus, allowing an athlete to train longer and harder, or reduce perceived exertion, or by altering cellular responses to exercise-induced stress.

01:18: In particular, supplements like dietary nitrate, buffering agents, and anti-oxidants, may modify the cellular signaling response to training by affecting acid-based balance, reactive oxygen species signaling, or redux status. But how significant is the impact of these supplements from a practical standpoint? How much is needed to achieve changes in performance? For that matter it is possible that these effects on cellular signaling may actually have a negative impact on the adaptive response to training.

01:50: These are not easy questions to answer, which is why I am happy to welcome Jeff Rothschild to the show. Jeff is a registered dietician, with a master's degree in Nutritional Sciences and a specialist in Sports Dietetics. He is also the creator of the humanOS Fasting program in our app. Jeff recently wrote a review examining the impact of dietary supplements on adaptations to endurance training and is here to discuss his findings of what they might mean for athletes and active people out there. So, Jeff, welcome to humanOS radio.

Jeff Rothschild - 02:23: Hey, Dan. It's always nice to chat with you.

Dan Pardi - 02:25: Actually, I have to say, "Welcome back," because you were a guest with Greg Potter on the subject of breakfast skipping, which was actually one of the most popular shows in our library.

Jeff Rothschild - 02:36: Cool.

Dan Pardi - 02:36: I'll reference that in show notes. What stimulated you to write this monster review?

Jeff Rothschild - 02:42: Like you said, I'm a registered dietician and I spent most of my time over the past five years or so working with people on an individual basis in a private practice setting. Athletes ranging from people just trying to complete their first 5K to Olympians, people competing at the World Championship level. So really a range of people. But there's a few common issues that come up. One of the things is what should I eat before exercise? But when I'm thinking of supplements, there's this handful of supplements... Well, let me take a step back. There's a ton of supplements that are out there, as anyone knows who's walked into a health foods store. Most of them probably don't work. But there is a handful that are pretty well supported by evidence to offer some kind of acute performance benefit.

03:22: The ones that typically come to mind, caffeine, sodium bicarbonate, beta alanine, creatine, these kind of things. Of course, when working with people that want to go faster... Again at any level, whether it's a recreational race or the Olympics, it's more fun when you go faster. There's certain things we would recommend.

03:38: But then someone asked me a question once, and it became kind of an obvious question, "If this helps me before a race, should I take it everyday?" It's a good question and I thought about it for a long time. And this the question in my head that at least went back a number of years. And there's really not nearly as much information on what happens if you take it every day, compared with just taking it for that day or for some things it might take a week or two weeks of loading, where we know, "Okay, if you take this for two weeks, or four weeks, or one week, you're going to be able to go faster." But does it interfere or enhance the long game? Especially with endurance training but any sport, you want to think about accumulating years of training and adaptations. So will this further the cause of the bigger picture or will this give me a short-term benefit for maybe a long-term negative effect?

Dan Pardi - 04:21: As I took a deeper dive into your review, that idea specifically struck me. Some supplement that could make the exercise in that moment feel easier or make you perform better could potentially lessen the training effect. We can dive into that more today. How did you decide what supplements to review for this purpose?

Jeff Rothschild - 04:41: It starts out with just a general inquiry and that was kind of my own curiosity and then I realized there was a lot of substance there that was worth writing a big paper about. Like I said, there's those handful that are always mentioned essentially in the same sentence, sodium bicarbonate, beta alanine as the buffering agents, dietary nitrate or beetroot juice, caffeine, creatine, anti-oxidants. Those are the ones that are I'd say more or less accepted that they, at least in some context, can offer some performance enhancement. Then from there, I [inaudible 00:05:08] study in a training capacity, so taking it for, let's say, at least three weeks, generally 3-12 weeks training studies, and measuring things that we care about, maybe antioxidant status, but especially performance.

05:20: You have to max all these markers of training and performance and/or performance itself. Once I dove in there it became clear that these ones are not even that well studied, but there's a handful of studies on most of those, and then there's a few other fringe ones that we mentioned in passing in the paper but aren't really very well studied.

Dan Pardi - 05:35: So many supplements exist. Fewer have research on them. So many that do exist that don't have the most research on them, they might not have an effect at all, or they could they just haven't undergone rigorous scientific review-

Jeff Rothschild - 05:48: Yeah.

Dan Pardi - 05:48: ... and how would you know that unless you actually could detect something immediate, and it's also hard to parse out the placebo effective. You purchase something that you think is going to affect your performance, because you read about it being able to do so. That in itself can cause perceived effects. Let's talk about buffering agents first. Tell us about what we're talking about here with buffering agents.

Jeff Rothschild - 06:11: There's a few more than these in the category, but generally the most commonly studied, and the most commonly used ones are beta alanine and sodium bicarbonate. Buffering, if you think back to chemistry it has to do with the age when we start exercising, especially at a higher intensity the pH drops, and that's part of the fatigue process. Let's say the fatigue is extremely complex, but let's just say when the pH drops, your muscles don't contract as well. If you start by raising the pH, so if you take baking soda, sodium bicarbonate is also baking soda, so that's a buffer, that can increase the pH which makes it more alkaline. So, if you start out with an increased pH and then it lowers by some amount through exercise you're not as low as if you started at a normal pH.

06:51: That's essentially what's happening, and so it allows increased training intensity typically, but also the increased pH, or the lack of a decrease in pH, can affect in some ways these mitochondrial adaptation, to explain that briefly.

07:03: The point largely of endurance training, maybe not the whole point but one of the key points, is to improve our mitochondrial function. So, we want our mitochondria, the things that make energy, we want them to get bigger, we want them to work better. There's some evidence that a decreased pH can interfere with some of those adaptations. So, by increasing the pH compared to, let's say, the same stimulus with a lower pH you might see better adaptation from that given workout.

Dan Pardi - 07:27: When you are training and exercising you are producing more hydrogen ions from the increased energy need. Increased hydrogen ions can then interfere with the contractile apparatus of the muscles, so that is one of the components that leads to fatigue. Secondarily, there are receptors can perceive hydrogen and have an effect on limiting the central ability in the brain to send a signal to muscles. So, you have two different fatigue mechanisms, central fatigue and peripheral fatigue, both of which are going to detect circulating acid. So, if you make your blood more alkaline ahead of, and during, the exercise, you can delay fatigue and train harder. But, the hydrogen stimulus is causing the adaptation, so if you're trying to get the maximal training effect, you might be able to train harder but are you limiting the stimulus that would help your body get more fit? If you train regularly with bicarbonate, what do we know about long term effects?

Jeff Rothschild - 08:17: There's one study that matched the training intensity. Of course, that would mean there would be a difference in pH, and in that case the bicarbonate helped the adaptations, but there's a few others that haven't shown effect. What it seems to really come down to, and this is the case with sodium bicarbonate and as well as some of the other supplements we'll talk about, is it will likely allow you to train harder. So, if you're doing, let's just say, an interval workout, maybe it's three minutes on and three minutes off at your maximal effort, you're going to create a lot of lactate, and related to that buffering capacity by taking bicarbonate, for example, it's going to allow you to create more lactate.

08:47: We should probably talk about lactic acid and lactate and that confusion, but lactate is a good thing. It's used as an energy source and it's used as a signaling molecule, and acidic part of it is what you just referred to as hydrogen ions. That's the part, the increased hydrogen ions, it's not from the lactic acid per se, but it's the increased hydrogen that is the "bad" stuff in our context.

09:08: The lactate is a good thing, so when you can create more lactate, by essentially pushing your glycolytic system harder, then that's going to likely lead to greater signaling.

Dan Pardi - 09:17: You would push your glycolytic system harder by training harder?

Jeff Rothschild - 09:20: Yeah. So, it would allow you to do ... Let's just say going back to that three-minute intervals, if we measured the wattage that you could do for three minutes on, three minutes off for, let's say, four to six intervals, it would very likely be higher if you've supplemented the sodium bicarbonate. So, the accumulation of that greater work output, probably combined with the increased lactate, circulating lactate levels, would probably lead to a greater training adaptation, probably through a number of mechanisms actually.

Dan Pardi - 09:45: Right? So when you're producing more lactic acid association of the lactate from the acid, the hydrogen, you are left with hydrogen ions, which lead to the acidity and fatigue, and a lactate which can be used as a fuel, but it also is serving as a signaling mechanism that can affect epigenetic regulation and gene transcription. So, that is also a signal promoting some of the enhancement in exercise function from stimulating lactate more regularly?

Jeff Rothschild - 10:08: Exactly. So, we're getting essentially less free hydrogen ions and more lactate relative to exercising in a normal condition.

Dan Pardi - 10:15: Interesting. So if you're taking sodium bicarbonate you could buffer the acid but still produce the lactate?

Jeff Rothschild - 10:20: Well, that's exactly right, and that's in the studies that don't tend to show an effect with, let's say, with bicarbonate or beta alanine. So beta alanine is kind of lumped into the same category, but it's a little bit different. That works more as an intracellular buffering agent, whereas bicarbonate is extracellular, so in-the-blood buffering agent. The biggest takeaway from this paper is that you need to drive more lactate in order to see the training adaptations, especially with regard to the buffering agents.

Dan Pardi - 10:44: Unless there's some sort of important signaling that is occurring from the acid itself you wouldn't necessarily be limiting the training effect by taking bicarbonate. In fact, you could be enhancing it?

Jeff Rothschild - 10:54: Right.

Dan Pardi - 10:55: You sort of have your cake and eat it too?

Jeff Rothschild - 10:57: That's what it seems like. The only, let's say, stipulation is that you got to work harder than you would have otherwise. So, if you just clamp the wattage, so if we said you're going to do three minutes on, three minutes off at, let's just say 300 Watts on a bike, then with or without sodium bicarbonate it probably won't make a difference. There's a chance that it might. To speculate, it would probably be more apparent in the lower intensity training, but that hasn't been well studied. If we just stick with interval training and the intensities are clamped, let's just say 300 Watts on and three minutes rest, with or without bicarbonate probably won't make a difference.

11:27: But, if it's three minutes at maximal effort, and you're going to essentially be able to create more watts, more work, during those three minutes that's probably how and why we're going to see a difference. Again, related to a few things, partly the lactate, probably the increased mechanical load and stress on the muscles. That's a good way to think of it. If you think about the ratio of research to actual usage in the real world, I would bet more research subjects have used it then just general population, because it tastes terrible and once you get past the taste, if you take too much you can go to the bathroom, or you might have to go to the bathroom very quickly.

11:56: It's around 200 to 400 mg/kg of body weight. So, usually it works out to about, for an average-sized person, about a tablespoon, but you can divide that across two or three servings to break it up a little bit. It's highly variable between people how much you need and how much you can tolerate, so be aware of that. Although it's uncomfortable, it's not like that being a downside so you have to go to the bathroom, but you want to just make sure you're in a good place to do that.

Dan Pardi - 12:18: It's hydrophilic so it's going to pull water towards it, and then you take too big of a dose it's just going to move right through you. When you're not in a good place when you can go to the bathroom you are in a bad situation.

Jeff Rothschild - 12:28: Yeah.

Dan Pardi - 12:29: Let me say one more thing about bicarbonate. There are now products that are potassium bicarbonate or some sort of mixture of different ions. So, it's not just sodium. You can lessen the sodium load. I actually do take a potassium bicarbonate. I prefer it. You can look for those on Amazon if you want to try this, but you don't have to necessarily have just sodium bicarbonate to get that effect. So, the bicarbonate is what's really probably driving a lot of benefit. Sodium could have an impact too. But anyway, tell us about beta alanine. What is it?

Jeff Rothschild - 12:55: It's also considered a buffering agent. Actually, there's a lot of different way that it can work. It's actually not even entirely clear. It can improve the calcium sensitivity in the muscles, it could reduce lipid peroxidation, it can affect pH, it can reduce perceived exertion, it's pretty interesting that there's a lot of ways that it can work. Now, one of the most important points, people might see it in pre-workout supplements a lot.

13:17: Really to be effective, if the dose is around three to six grams per day for around four weeks before you start seeing a noticeable improvement. If you take an acute dose, you might feel a tingling thing, which is harmless, which makes people think it's working. So, a lot of pre-workouts that combine that with caffeine, it's really the caffeine that's working and you get a tingling feeling. So, you think, "Oh, this must be doing a ton." But acutely, that tingling does nothing beneficial, probably nothing harmful, like you said, so that's I think an important point.

13:43: So, when people just have it in pre-workout to get the actual benefits it, it needs to be around four to six grams or even more per day for at least around four weeks.

Dan Pardi - 13:53: Do people level up with it? You start taking four to six grams right from day one?

Jeff Rothschild - 13:57: Because of the tingling, you might want to work into it slowly. But typically with that four to six grams, you would want to split it into three to four doses per day, so it's a bit of a hassle. I definitely have some clients that would use it. It can be helpful for the right person for sure. It can also then allow you to sustain exercise at a higher intensity, so you can trial at a greater training volume. From its practical standpoint, it can let you do more work during these high intensity interval training type of workouts.

14:22: And then again, that accumulated work is what will give you additional benefit beyond just the interval training or just taking it by itself. There's a figure in the paper that shows improvement from baseline with beta alanine. So, if you just take beta alanine, and let's say it's a four kilometer time trial, so it's a short time trial, you might feel like a one and a half or so percent improvement in performance just taking beta alanine. Then if you do just sprint training alone for four weeks or five weeks, you would see about a 3% improvement from baseline.

14:49: So, we can go from about a one and a half to 3% improvement, and then if you do a combination of sprint training with beta alanine, that might pump you up to about a 4% improvement from baseline. They really are separate, but additive effects. Now, the important point there is if you do the exact same training with or without it, it's probably not going to have any difference. Not everyone has access to wattage, but you can think of it as running speed or whatever that unit of work is.

15:11: If you do a set amount, a clamped amount in these intervals, you'll probably not going to see any improvement. You'll still see some improvement from the training itself, but not necessarily from the supplements. Really the key there in my opinion and based on what's on in this paper is to allow this open ended efforts that allow maximum work rates to elevate blood lactate compared to a placebo.

Dan Pardi - 15:31: Has there been any work looking at the combination of beta alanine and sodium bicarbonate?

Jeff Rothschild - 15:36: There is not a ton of training studies, but it's a bit unclear. In the studies that we included in this paper, they were supervised training. All but one study that have used this co-ingestion protocols that participant training sessions were not monitored. So, we don't know. Were they doing more work? Were they doing less work? Were they doing the same? That's a really important differentiator between the training to understand what's happening.

15:56: It's really hard to say. They tend to have similar improvements, so you can use one or the other and both weren't helpful. If you have a research study of a specific type of exercise test, so it's probably that one or the other will benefit in this type of exercise test. But in practicality, if you think of a cycling race or a triathlon, there is probably types of intervals and types of efforts you do where one might be a little bit more helpful than the others.

16:18: I do think, if I was working with an athlete that was really everything he needed to be, as good as it could be, there's probably a reason to do both. But since we're talking about context of training, probably one or the other is just fine.

Dan Pardi - 16:31: I found it interesting that beta alanine increases inner muscular stores of carnosine. Harkening back to my show with Pankaj Kapahi from the book on AGEs or advanced glycation end products, carnosine can help prevent the formation of AGEs.

Jeff Rothschild - 16:46: Yeah. That's part of what we talked about initially. There could be some potentially less beneficial effects because it can act as an antioxidant. And the same thing with beetroot juice. So, there's potential for getting less of a training effect. So, especially again if you're clamping these intervals you keep referring to, but again if the training is equated, you might see negative effects because you're not going to get that same stimulus. The work out you get better because inside your muscles during and after your workout, stuff happens to keep it simple.

17:14: There's a bunch of unbelievably complex and elegant amount of signaling that happens, and if you interfere with that and if you dampen that, that's one of the reasons again the way we want to look at this paper, are these signals dampened? Are they increased? So, from the antioxidant perspective, it's possible, but beta alanine could dampen some of that signally. And it's also possible that maybe the combination of allowing you think with a little harder, create more lactate, but then dampening the oxidant signaling, there's some counteracting effects there.

Dan Pardi - 17:40: It's such a difficult thing to assess because if you're training at a very high volume, then that perhaps could be a good thing. If you're not training at a high volume, you're lessening training effect. It's really difficult to know how to best intervene-

Jeff Rothschild - 17:53: Exactly.

Dan Pardi - 17:53: ... without direct clinical trials to show that it is beneficial in this group of people with this fitness level, and this training amount. I don't think we can assess that on our own very easily.

Jeff Rothschild - 18:03: No. As a take away so far of the bicarbonate and the beta alanine, if you're doing intervals that you're trying to push your efforts, than there probably is a benefit, and I don't think there's a downside. At the very least, it's probably not harmful, but maybe not beneficial. I don't see a downside to hang on beta alanine for example.

Dan Pardi - 18:20: What's the minimal length event that you think beta alanine ingestion over four weeks could augment?

Jeff Rothschild - 18:27: One minute to 10 minutes is probably where it has the most effect.

Dan Pardi - 18:30: Got it.

Jeff Rothschild - 18:30: Now, people that rule out let's say triathlon, but especially with Olympic triathlon or that's draft legal, there's a lot of surges or you might be running up a hill or in cycling, road racing, it's a lot of short efforts. It's not like let's say a five hour race in a Tour de France. It's not a five hour steady effort. It's a series of these sharp efforts, so I do think there's a benefit there. But as far as how much of an effort that it's a duration of interval that it's going to really help. It seems to be with both bicarbonate and beta alanine in that one to 10 minute range.

Dan Pardi - 18:57: Very interesting. Let's move onto dietary nitrate. This is a subject that I've covered in a different show with Jonathan Burdette, neuroradiologist from Wake Forest, he was looking at the addition of beet root juice supplementation in a group of older people. And interestingly, looking at their brains under functional magnetic resonance imaging that he noticed that the functional connectivity of brain regions was improved with the addition of beetroot juice prior to exercise training. So, he had a control group three times a week, 50 minutes exercise, then another group, three times a week, 50 minutes of exercise plus beetroot juice.

19:32: Those that had beetroot had better brain connectivity. We do know that beetroot juice is a vasodilator, so it probably can get more blood flow into the brain. With that context in mind, let's talk about dietary nitrate in the sports performance context. So, tell us about how you think it's working and what the mechanisms are perceived to be.

Jeff Rothschild - 19:53: Again, from a practical standpoint of someone using it for training, the increased training intensity that it allows is going to be the important thing. Again, if you clamp your training, probably not going to have as much of a difference, especially with high intensity training.

Dan Pardi - 20:06: Let's drill into that term a little bit, clamping training, just so people get it. Explain that in non-expert terms.

Jeff Rothschild - 20:12: Sure. Yeah, so let's think of it as with running. So, if you were going to go on the treadmill at the gym and do, let's say intervals, maybe you're running three minutes on and then resting a minute, you might set the treadmill at a certain speed, eight miles an hour, 10 miles an hour, whatever it is that's appropriate for you and you'll run at that speed. If you were outside on a track, and I said, "Run it three minutes as fast as you can and then rest," chances are, one, you probably won't hold the same speed but you might actually run faster than 10 miles an hour, especially if you were feeling good or if you maybe had some supplement that allowed you to give a little bit more. So, when we say clamping, it's essentially would be just imagine setting the treadmill at a certain speed and then whether you take a supplement or not, you're going to run exactly at that speed.

20:51: Whereas unclamping would be three minutes as fast as you can and it's easier to think of it on a track or do it on a track or some people, I'm sure, can do it on a treadmill where they just keep inching it up, but even then I think there's a tendency to probably just leave it when you would have otherwise adjusted your speed outside.

21:06: One of the most interesting things, also, I think about dietary nitrate is people tend to use it interchangeably with beet root juice. Beet root juice is the most well studied form. Dietary nitrates, though, are found in beet root and spinach, a number of vegetables and it's potentially related to a lot of the benefit of vegetables, potentially related to the dietary nitrate content, at least with some of the vegetables, but nitrate is just one element of beet root juice. Interestingly, the studies are not the same when you give a nitrate salt and beet root juice. So, while that's kind of a nuance point, because most people would probably take some kind of beet root supplement, the nitrate certainly has something to do with it, but it's not the only thing. So, there's other polyphenols in the beet root juice.

Dan Pardi - 21:43: Betalains, which just fairly interesting, beets, chard, Amaranthus, they are a different type of phytochemical, and is it just the dietary nitrate or is it the dietary nitrate plus some of the phytochemicals that come along with it?

Jeff Rothschild - 21:54: Yeah, I really think it is and there's, I think, a paragraph or two somewhere in there that shows the studies that used the nitrate salt, sort of testing nitrate or something equated for nitrogen load. It's just different effects. So, part of it from the practical standpoint is the training intensity, but also at submaximal exercise. So, lower intensity, it tends to be reduced oxygen cost and that's probably similar to what, they're getting more blood flow to the brain. You're getting blood flow and oxygen to your muscles as a vassal dilation effect. This might be some benefit from a performance standpoint in lower intensity long duration exercise but if we're talking about these training adaptations, it probably comes again from this increased training length, which it should allow you to do. If you're doing short efforts, anywhere between even 15 seconds to four-minute intervals, you'll probably be able to go harder and therefore create that bigger stimulus.

22:37: Now, there's a few studies that showed muscle fiber-type changes, so that's one of the things that also happens during advanced training. We have slow twitch and fast twitch and then we have these middle ones. Endurance training in general leans your muscles towards the slower twitch endurance type of muscle and this might actually help potentiate that change even a little bit more. So, it's less well examined, but it might be a potential benefit for someone doing a longer duration, lower intensity training. You might get these muscle fiber-type changes as well.

Dan Pardi - 23:04: Interesting. If you are a truly glycolytic athlete and you have short intensity, very high, you perhaps might not want to take in beetroot juice?

Jeff Rothschild - 23:13: No, I actually wouldn't say that. I guess I kind of insinuated that but I think that's because a lot of your training would be in that high intensity that will actually help that type of training through the oxygen kinetics. So, I think you'd only see that if you were doing a lot of aerobic training. That's a little bit of speculation. I think there is still benefit from a glycolytic. A team sport athlete, there's probably some benefits still to take it.

Dan Pardi - 23:35: We have a couple of different mechanisms here, increase in blood flow, decreased oxygen, cost of muscle contraction. Can it also have an effect on the efficiency of mitochondria in producing energy?

Jeff Rothschild - 23:45: Yeah, it can. It seems to be in it. That's a really interesting thing and it can also even potentially increase mitochondrial biogenesis, so making more mitochondria. It's still maybe a little less clear, especially in the context of training adaptations, but there's, yeah, I would say a handful of different ways that it might be beneficial.

Dan Pardi - 24:00: This might be one of those supplements, where unlike sodium bicarbonate, which seems to not have a downside, so you do get both within exercise session enhancement of intensity, and because it's not necessarily limiting lactate production, you probably are not causing a consequence to using it in terms of long term adaptation, but with dietary nitrate there could be by reducing the oxidative cost of the exercise?

Jeff Rothschild - 24:25: Potentially, but I would say that there's still no evidence that it impairs adaptation. So, at worst, I should say, it's like a net neutral and there might still be some other benefits to getting the beet root juice in your diet, for example, especially because most people don't consume enough, probably, vegetables.

24:38: So, then there's a couple other points where it might work slightly differently in people that are habitually really high vegetable eaters versus people that don't eat any vegetables. Also, elite athletes probably need more of beet root juice to get the same effect from recreational athletes. So, there's a lot of nuance there but if I think back to the practicality, taking enough of it to get a response from it, different products also have different amounts of nitrogen in it.

25:00: So, there's some published graphs showing that there's huge variation in how much nitrate is actually in the 20 different beet root products that are on the market. If you take enough, it's still a net benefit, again, from probably other health-related reasons, your cardiovascular health. I don't think there's much of a downside. It can be a little expensive and if we're thinking in terms of training, it's either going to help but I don't really think it would hurt. In a small percentage of people, there can also be some GI distress.

Dan Pardi - 25:23: With sodium bicarbonate, you can take it in smaller doses starting 90 minutes out leading up to the event with beta alanine. You have to take it probably three or four weeks before you start to then increase the amount of beta alanine or a byproduct of it intercellularly but you do ultimately see buffering and an improvement in high intensity exercise capacity. When would a person take dietary nitrate and is it simply an acute effect or is there also a period where you, as you're taking it, you get an increased benefit over time?

Jeff Rothschild - 25:50: Great question. There's probably, it's both acute and chronic, so if you take one dose about two and a half hours before you want it to do its thing, then that can work. A more effective way would be to take it for three to seven days prior to your marathon or something. Then you'd be more likely to see an effect that way. So, that's for the acute effect of just enhancing performance for the training. There's no reason you just can't make it part of your diet.

26:10: I still feel a little reluctant to say that but it seems like an irresponsible thing to say but there's no clear reason why it would be a problem to continue taking. That said, I mean, you could still imagine some internal downregulation potentially. I might advise someone to say take it when you're doing hard training and then maybe back it off if you have a recovery week. So, if someone's training like a higher level athlete might be training three hard weeks on and an easy week, maybe taking it during the hard weeks and then backing it off on the easy week.

Dan Pardi - 26:33: In the face of not perfect information, that seems like a reasonable strategy.

Jeff Rothschild - 26:37: Yeah.

Dan Pardi - 26:37: Perfect meaning very detailed information on different populations over time. I mean, it's a food. You can obviously reduce it into extracts or parts of that food, like just the nitrate, but if you're taking beet, then it is food. Keep that in mind.

Jeff Rothschild - 26:49: Yeah.

Dan Pardi - 26:50: Let's talk about antioxidants. Why would people think that these could be beneficial in exercise?

Jeff Rothschild - 26:56: Up until now, those first three supplements, they seem to really help by increasing the work, by allowing increased training stimulus, and you can work harder. In this case, people think if exercise causes oxidation, oxidative stress, then we should take antioxidants to combat that. [inaudible 00:27:12] that seems to become a popular idea. A few minutes ago I mentioned stuff happens inside the muscle during exercise. That stuff largely is oxidant signaling, reactive oxygen species. They're the messengers within the muscle, among others, that tell your body, essentially, it's time to adapt and get stronger, and get fit, or build more mitochondria. So, if you take antioxidants, potentially dampening that signal, you're going to get less of a training effect. You're not going to respond to exercise in the same way.

Dan Pardi - 27:37: My show with professor Dr. Michael Ristau, who did some of the seminal work in that area.

Jeff Rothschild - 27:41: Yeah. Oh absolutely. Yeah.

Dan Pardi - 27:42: I'll just remind people of that if they didn't hear that, or can't remember, but some of the earlier studies had people train with and without antioxidants. The placebo group that trained over the course of five or six weeks didn't take antioxidants, had all the expected benefits of exercise, increasing insulin sensitivity, et cetera. Those that did take the antioxidants essentially had the training effect obliterated. That caught people's attention, because the idea that oxidations were simply a bad thing and to limit them as much as possible, we learned very clearly that they're providing important signals that then promote adaptation that we do want.

Jeff Rothschild - 28:18: I would say that's extremely clear in the literature, in the scientific literature, but that hasn't been communicated well to the public. There's certainly been articles about it, but if you see the amount of antioxidants people still take on a regular basis pretty shocking in some ways. Knowing just even with the simple things we just talked about, and then all the clients I've seen over the past, let's just say, several years, so many people come and take these huge doses of vitamin C, vitamin E. One of the interesting things I certainly was aware of that all things [inaudible 00:28:43] before I started looking at the paper. But there actually are no real training studies showing a performance detriment, so the VO2 max, those things, still improve similarly, but there is a lot of evidence showing the adaptations of the training don't improve the same way.

28:57: There's a few ways to take that. It might be that you just need longer time to show that the one group is going to improve more than the other, because it's hard to do long training studies, or it might be that there's some of the signaling is impaired but your body has these fail-safes. There's different ways that your body adapts, so even if one pathway is blunted there's another pathway that's still doing all the signaling that's in the mechanical stress of contraction. That's going to be signaling as well. It's complex. There's no reason to take antioxidants in this context of training adaptation, or really for any reason really, but it's interesting that it's also not as clear as they will blunt a lot of patients, because there's all the studies that I've looked at the VO2 max, there's none that have shown any differences that I've found.

Dan Pardi - 29:39: At a lecture at the Society for Neuroscience in 2004, on obesity, Dr. Berto gave a keynote lecture talking about how the mechanisms regulating obesity are complex, redundant, and distributed. Then that redundancy comment stuck with me. For these fundamental systems in the body and our physiology it's not just one signal is responsible for that entire effect but can be oftentimes multiple signals that are at play. Some other limitations about Dr. Ristau's work is that it was in a population that wasn't trained. So, what about population who is? What about different higher intensity levels? You could have imagined those that are doing ultra-marathon, multi-day challenges where antioxidants could actually have a beneficial effect.

Jeff Rothschild - 30:22: Absolutely.

Dan Pardi - 30:22: But again, I'd like to see more specific work on that to feel confident in making any sort of recommendation there.

Jeff Rothschild - 30:27: I don't know if it was from Dr. Ristau, but someone is a great figure in one of the papers discussing all this, and said probably some amount of oxidant stimulus that is a good amount and then pass that, like say an ultra-marathon where it's too much and antioxidants really would be beneficial. Knowing where that line is really tricky. There are so many different categories in these pathways. So, there's been some really interesting research from Greece, and they do a lot of tailored antioxidant treatments. So, measuring people and seeing which things are high or low and showing improved health outcomes, and training outcomes, when you adjust really specifically for them, more than the other supplement categories here I think are super hard to give some blanket statements here.

Dan Pardi - 31:06: My recommendation for those who are listening, until we do have more knowledge there I would let that research play out a little bit before mucking around with it.

Jeff Rothschild - 31:14: Yeah. An important takeaway is exercise is an antioxidant itself, and one of the most interesting findings related to this I've come across is that there was a pretty big study, and I don't have it in front of me, but looking at athletes. Number of years training was the greatest predictor of antioxidant status, so endogenous antioxidant status, so what our body's capable of just on its own naturally, or internally, the number of years training is the best predictor of that, more so than any type of diet, or any type of supplement someone was taking. Basically training itself is what increases that internal defense system. Really, exercise is the way to increase your own antioxidant status.

Dan Pardi - 31:47: If you think about what the oxidant signals are doing from exercise, they are stimulating pro-survival pathways that then increase the body's endogenous antioxidant capacity.

Jeff Rothschild - 31:56: Yep, exactly.

Dan Pardi - 31:58: So, this is a nice segue from primary antioxidants, which are agents that directly quench free radicals and the cytosol into polyphenols, which are considered secondary antioxidants. They might have some primary antioxidant activity themselves, but they're primarily basically like exercise in that they cause free radicals to be induced and then that induces our body's ability to then enhance its own antioxidant capacity. Let's talk about what we know about polyphenols in the context of sports performance.

Jeff Rothschild - 32:27: Not a lot. Even among the polyphenols there's different ones, so we can think about green tea extract, and resveratrol. Green tea may be an easier one to wrap our head around first. That probably does favor fat oxidation. That doesn't mean it's going to help you lose weight, or lose fat, per se, but if you're doing a submaximal exercise, let's say a marathon-pace type of jogging and you've taken an appropriate amount of green tea extract, then you probably will be burning more fat compared with carbohydrate relative to what you would be if you hadn't taken that. So there's potential for some benefit there.

Dan Pardi - 32:56: The idea you want to be in the fat burning zone, because if you're burning fat then you're going to reduce fat. Tell me about your thoughts if that is the correct way to think about this.

Jeff Rothschild - 33:06: That's a good question. I think a yes and no. Actually, if we then think of the podcast with Javier Gonzalez, if you do... What is really interesting that he talked about his recent findings, if you do fasted exercise, if you burn more of your liver carbohydrate stores you're going to eat more at lunch than if you did fasted exercise and didn't burn as much of your liver exercise. You're doing the same exercise but burning more fat relative to carbohydrate, you're not going to have the same compensatory eating. So, there's some potential there for not burning through your liver glycogen during a morning fasted endurance workout. There may be some benefit in the big picture ... No, I've never suggested green tea extract to any weight-loss client, so I guess I should have just started with that. Whether or not burning more fat during exercise is a requisite for losing fat, I don't think that's the case, and I think, again, it relates probably to that liver glycogen story. That's a relatively new thing to be understood. Those are my brief thoughts on that.

Dan Pardi - 33:56: I know it's a little bit of a departure of the idea that do these have an enhancement in exercise performance or adaptation to exercise? We can circle back there now, but it sounds like we just have less work on it.

Jeff Rothschild - 34:07: Then, if we side step to resveratrol, which is also a polyphenol, it does activate SIRT1 and can shift muscle fibers towards that oxidative phenotype, so things that are similar to exercise in a sense. But then, only two studies of taking it during exercise, it blunts these improvements, so I can't give people much practical recommendations other than that I would not take it, or would not recommend it for people generally.

Dan Pardi - 34:27: Anything else interesting about green tea extract? It can affect the ability of the body to burn more fat during exercise. Whether or not that's a good thing, not entirely sure. Does it do anything else that might actually enhance exercise?

Jeff Rothschild - 34:40: It can favor beta fat oxidation, and so if there was maybe like a time to exhaustion at a low intensity if you're maybe going for a hike. I don't know that it's that practically useful, to be honest.

Dan Pardi - 34:50: Yeah. Okay, cool. Now let's move to creatine. What is creatine, and what does it mostly used for?

Jeff Rothschild - 34:59: It's mostly thought of as for bodybuilders, but it's amazing. All the different things it does, can even affect sperm motility, I believe. So ranging from sleep to sperm quality. It's functions as part of the energy pathway. If there is a miracle supplement in this of what we've been talking about, I suppose it would be that. Although that said, in the context of endurance training, it's not very well studied.

35:19: Realistically, it can potentially help by allowing that increase in intensity. It might help you improve energy production, so these 15-seconds performing intervals. Again, you think it's not [inaudible 00:35:28] probably you're going to see benefit. But it also can act as an antioxidant. It can reduce [inaudible 00:35:33] oxidation. There's only a few training studies and just not that much for differences, but I think they're not... let's say looking at the right things or the long enough time.

35:40: But if we think of it as a... We have these different energy systems and it's a key part of our short-term energy system. So that if you were to stand up right now or jump onto a desk, that would be the creatine phosphate system that provided most of that energy. So, if we're doing any short sprints, we can feel depleted after eight or 12 seconds and recover that creatine phosphate system is what's being replenished them. And then allows that the [inaudible 00:36:01] to be repeated sprints.

36:02: By taking creatine, it essentially increases the pool in our muscles above ... Depending on your diet, it might be walking around, let's say half-full or something. And by taking creatine over time it increases so you have a greater pool to pull from. It's effects are so wide ranging. I think even there's some benefit in [inaudible 00:36:17] and aerobic metabolism, so people wouldn't think that it benefits cycling, but it probably could.

Dan Pardi - 36:22: We think of it relative to something called the Lowman reaction. It's pre-glycolytic, but it's the energy that you're going to use for a burst of activity less than 10 or 15 seconds. If you take exogenous creatine in supplemental form, then you can store more of it in your muscles. That pulls water in with it. That in itself might actually be part of the training benefit. If you're increasing mass within the muscles, you might actually be able to have greater contractile force, simply because the muscles are more turgid are filled with water. And then that might allow for a greater training intensity, which might allow for a greater stimulus of protein synthesis. It is really an interesting one.

Jeff Rothschild - 36:58: One of the concerns is that water weight. There's a great study in well-trained cyclists with carb-loading and creatine-loading. Both carb-loading and creatine-loading will cause some increased water retention, but it's useful water. It's in your muscles. Despite two and a half percent increase in body mass, there was a greater power output during these sprints within a 120 kilometer time trials.

37:16: What that means is along 120 kilometer time trial, so think of it as a long race, but there's some sprints in between. You're going to be able to sprint better in the midst of a cycling race or running race. And also that didn't affect their uphill cycling [crosstalk 00:37:30]. The weight is usually what's important for uphill cycling, but didn't impair that cycling, that small amount of extra weight, but it allowed them to sprint better, even in the context of a road cyclist doing long events, there is some benefit there.

Dan Pardi - 37:42: I have taken it before from a long time ago. I'm a responder so I'll gain 10 or 15 pounds when I take it.

Jeff Rothschild - 37:49: Oh whoa.

Dan Pardi - 37:49: Every time all gain about that much weight.

Jeff Rothschild - 37:51: Wow, yeah.

Dan Pardi - 37:53: [crosstalk 00:37:52] and go up a jacket size.

Jeff Rothschild - 37:54: That's interesting. Yeah, it doesn't affect me. I pretty much just stay on it. And separate from our conversation with regard to supplemental training, but Chris Masterjohn has talked about people with MTHFR deficiencies and creatine is it the role in the methylation pathway and it affects your need for choline. Anyone with low energy, creatine could help, or it effects the choline and methyl donor needs.

Dan Pardi - 38:12: That's great. Let's talk about caffeine. 80% of the United States takes some form of caffeine daily. The most widely used supplement, but it's also definitely discussed in the context of sports performance. What do we know about it?

Jeff Rothschild - 38:26: It's pretty clearly, now that this ... some will argue based on the genetics, but pretty clearly enhances endurance performance for around 2-3%. Anywhere from like in six-minute time trial performance to two and a half hour time trial performance. So, it's pretty clear. Again, you can find studies that don't do it, in fact, where you can show in effect that some genetic types do better. But generally speaking, it's pretty clear that it works, anywhere between three to six milligrams per kilogram, which to me, just seems crazy high, because I'm sensitive to caffeine. So for me, one milligram per kilogram will have a nice effect on me.

38:57: It's suggested that habitual caffeine use will decrease its efficacy. And I've heard of athletes, some who say they don't take any caffeine for a week or two weeks before a race. It doesn't seem to be necessary. You might have to take a little bit more than if you were off it. But it will help performance, whether you're habitually low, moderate, or high consumers of caffeine, even though it's a recent study that gave caffeine every day for 20 days and it continued to produce the ergogenic effects. Now there has not been any training studies, which is so interesting. There was one with serious design flaws, the groups weren't controlled for caffeine, so there wasn't any difference in the caffeine intake.

Dan Pardi - 39:29: I see.

Jeff Rothschild - 39:30: Really effectively, there's been no training studies in caffeine within the [inaudible 00:39:34] pathways that we've talked about here with endurance training. There's no reason to think that it wouldn't be beneficial. It generally works. There's a number of ways that it's suggested to work, but generally it seems to be that eventually you can lower the perceived effort of our guts. You're going to be able to do more work during an interval workout, create more lactate, all these things, if you're taking caffeine, that's probably how it works. There's no reason to think that you should not take it before training, although it's really hasn't been studied, similar to the antioxidant training study or the beta alanine.

Dan Pardi - 40:02: Similar to the beet root juice, right. Beet root, we were talking about, it's has a high level of nitrate that can birth nitric oxide. But then with beets you also have betalains and other phytonutrients that then could also be secondarily affecting performance. If you think of caffeine, you tend to think of coffee, but it also is in teas. Teas and coffee both have other substances in there that could be affecting... And there has been some interesting research, not necessarily in the sports performance context, looking at the differences between just taking caffeine and taking things like coffee and teas. I like to get my caffeine in the form of coffee and not a caffeine pill.

Jeff Rothschild - 40:38: I tend to go with the caffeine pill. With caffeine, the theanine actually can have its own effects. As far as sports performance, I would say acutely caffeine pills or coffee or however it comes, they all seem to have the same effect, so the short term performance impact is roughly the same, but I think there's a real good case to be made that the longterm effects of the polyphenols in it, tea or coffee, would probably have some additional, probably beneficial effects with regard to [crosstalk 00:41:03], certainly beneficial effects, pretty clear in terms of other health related things, but as far as our training adaptations here, most likely.

Dan Pardi - 41:09: Yeah, that's good to know. Coffee beans have phenylindanes in them, which have been shown to reduce beta amyloid and Tau aggregation, so that could prevent Alzheimer's disease. We see a decreased risk of mortality for longterm coffee consumers, and then it also has chlorogenic acid, which has interesting effects on diabetes and weight. So you could be getting additional benefits in addition to the caffeine with your coffee. I have a cup of coffee usually before I work out, but only one in the morning and then I cut it off so doesn't affect my sleep at night.

41:36: Jeff, is there anything outside of what we've talked about that has caught your interest?

Jeff Rothschild - 41:40: There's a product called LactiGo, which is a topical carnosine. Just take a step back to our beta LNA conversation, we take beta alanine, but it actually, what it's doing is raising carnosine in our muscles. It works better to take the beta alanine, which is the limiting factor compared to taking carnosine, which would be metabolized and not make it to the muscle the same way.

41:58: So anyway, it's pain, to a point where I would say beta alanine four times a day for four weeks with a little bit of tingling before you potentially see these changes. So there's a topical gel that purports to get it right into your muscle. They're doing clinical trials to show the efficacy, but that's pretty interesting because it really saves a whole lot of trouble.

Dan Pardi - 42:16: So looking at it now theoretically, you could take it less frequently and it might have a faster effect?

Jeff Rothschild - 42:23: It would be... in theory an acute effect, and personally I do think it has those effects, but I want to see some studies. Beyond that, my interest now more specifically is, we mentioned I'm doing my PhD research in training adaption, both the effects of nutrition and [inaudible 00:42:35] on the studies that Javier Gonzales has been doing at the lab, but a little bit different angles on them; looking at faster training and eating carbohydrate beforehand or just protein beforehand.

42:44: Again, it's the same concept we talked about; there's signaling that happens inside your muscle and it can be related to the energy intensity, the volume, the substrate metabolism, so your energy [inaudible 00:42:54] pathways, but both supplements can affect also food and then how much your muscle is contracting. All these things that are affected by supplements can also be affected by food; do you eat beforehand? Do you not eat beforehand, but if you eat, are you having toast and a banana? Are you eating eggs? So that's really where my focus has shifted towards.

Dan Pardi - 43:10: Well, with my conversation with Keith Barr, professor at UC Davis, he was talking about the ingestion of collagen 15 minutes prior to doing some sort of exercise and the benefit that that has on tendons, so where things like whey protein and other forms of protein, you want to have them within a window after exercise to support muscle printing synthesis because the tendons are relatively avascular, meaning they don't have good blood flow supply. The way that they get collagen into those fibers to strengthen them is almost like a sponge.

43:43: Imagine you're doing some jump rope and you have collagen peptides 15 minutes beforehand, you're going to get more collagen into your achilles tendon. Once it's in the bloodstream, it's going to pull that into the ligaments and that's going to cause them to be stronger over time.

Jeff Rothschild - 43:58: That is an excellent show. I think I listened to it twice, but it's 15 grams of collagen about 60 minutes beforehand. It'll be ... work a little bit better.

Dan Pardi - 44:05: Oh, wonderful. Thank you. So you listen to it twice?

Jeff Rothschild - 44:08: Yeah.

Dan Pardi - 44:09: Good. Yeah. So 15 grams of collagen 60 minutes before. Good clarification there.

Jeff Rothschild - 44:14: I think 45 to 60 minutes if I recall, but yeah [crosstalk 00:44:19] it needs a little more time, but anyway, it's exactly right; what we're taking in our body, whether it's supplement or whether it's a food supplement, like an [inaudible 00:44:25] collagen or even carbohydrate or protein, it's affecting the stuff that happens inside our muscle [inaudible 00:44:30] exercise. It has been underappreciated until I'd say fairly recently.

Dan Pardi - 44:34: After the Javier Gonzalez show, I've been playing around with the after intense exercise ingestion of some fructose to restore muscle liver glycogen. Fructose does restore liver glycogen well if you can replete your liver glycogen stores that have a positive effect on leptin signaling, you can maintain your leptin signaling and that might actually lead to faster body fat loss in response to your high exercise training. I have to say, and [inaudible 00:45:02] not a lot of experience with it, I do notice that if I have a coconut water right after an intense exercise training, usually I won't be hungry for half an hour after exercising and then I'll be really, really hungry and with the addition of the coconut water then I feel it's totally normal and fun, like I did an exercise that day.

Jeff Rothschild - 45:17: It's Interesting. Yeah.

Dan Pardi - 45:19: Well Jeff, this is really interesting stuff, and to circle back to a key takeaway here, we talked about the acute effects to that question that you got which stimulated this deep dive, what are the supplements that you have people use regularly versus conditionally?

Jeff Rothschild - 45:36: We've got to take a hypothetical context of maybe someone who trains a lot, maybe not a professional athlete, but someone who's doing a lot of endurance training, let's just say seven to 15 hours a week or more, I think beta alanine is something that could definitely stay on. Caffeine before workouts, creatine, something that could stay on and maybe reduce, I would say those three, and then some... and then maybe the bicarb the night before our workouts.

45:58: I'd be fine with someone essentially just taking bicarbonate before every workout, but really that tastes... that stuff, I wouldn't want to ask someone to take that all the time. Generally, at least before hard workouts, they can add that in. Creatine and beta alanine just as the daily thing, of course goes without saying, assuming there's no other health issues, right? [inaudible 00:46:15] someone who's otherwise healthy [inaudible 00:46:16], but they... the creatine just daily, beta alanine daily, caffeine as desired, and then if you want to bump up and add the bicarb before a hard workout, that would be really nice.

Dan Pardi - 46:27: I know this was an absolute bear of a review paper too. How long did it take you?

Jeff Rothschild - 46:31: Oh gosh. I've thought about trying to add up the hours because the Microsoft Word document will accumulate the minutes, but I'd be afraid to... I mean a year off and on, but just it. Part of me is curious, a part of me doesn't want to know how many hours.

Dan Pardi - 46:43: I really appreciate you coming on Jeff and your work to collaborate with us at humanOS, it's greatly appreciated.

Jeff Rothschild - 46:49: My pleasure.