Transcription
Hello and welcome back to our final sport nutrition lecture in our online series on the topic of sport nutrition supplements. Now, many of us are probably familiar with the term "supplement," but the term supplement is some sort of substance that is added to a normal diet to try to maybe fill in some of the gaps, so to speak, dietarily, that an athlete or an exerciser may not be completely getting from their food sources and from their macro nutrient and micro nutrient intakes via their food sources.
A lot of times, the way we think about sport nutrition supplements are those that are meant to improve performance. But before we talk specifically about substances that are meant to improve performance, we should begin by considering exactly what kind of criteria it takes for supplements to be put on the market. And I think it's worth comparison here, given that a lot of supplements sometimes, or a lot of people perceive certain supplements to work like drugs, or to mitigate disease, or to produce a given outcome. In the context of exercise science, maybe we think about this in terms of performance. But I think that because of those utilities and views in the sport nutrition market on the role of supplements, it's important to understand the difference.
And as we all will know from our research methods classes, some of you may be involved in research or may have been involved or have looked at several clinical trials before. But long story short, for a drug to be to get the approval of the Food and Drug Administration, there's an extensive process that has to be undergone for that to happen: clinical trials in both animals and humans, and then of course, very robust methodological and controlled studies that will help us to determine whether or not the drug is safe and how best to use it.
But when it comes to supplements, the Food and Drug Administration used to not get involved in this particular market at all. So, well, I'll sometimes say that the supplement industry is the wild, wild west. It certainly is a little bit more controlled now than it used to be. And as of 1999, the Food and Drug Administration really started to crack down or administer some more rules for what must be on a sports nutrition label, or what types of information have to be provided about a sport nutrition supplement for it to go on the market.
And so, some of these things you are pretty simple. The first is the easiest, that that the statement that it is actually a dietary supplement, followed by exactly what is in it, or the statement of identity. And then of course, they have to tell you how much or how many servings are in it, and what size of a serving is. And then the biggest gray area is that they have to declare some reasonable expectation of safety. So, a reasonable expectation of safety meaning that there are not any adverse effects, and if there are any potential adverse effects, that those adverse effects are clearly stated and within reason to be able to safely keep this supplement on the market for most individuals.
Now, one thing supplement companies are able to do without much regulation is make claims. And perhaps the most important claim that sport nutrition supplements make, or most sport nutrition supplements make, is that they are a good ergogenic aid, being those that improve performance or exercise capacity in some way, shape, or form. And if this is the case, you would hope that the has a substantial body of quality scientific evidence that specifies the types of performance and the parameters for usage. But unfortunately, this is lacking for most of the ergogenic aids on the market today.
And when we want to then take a look at some ergogenic aids that do have at least some proven benefits, I think it's important that we kind of break these down. Here's the list of ergogenic aids that we're going to investigate today, and I'll go ahead and tell you that there is at least some proven ergogenic benefit of each one of these sport nutrition supplements. But when we're talking about the level of quality scientific evidence that is needed to really know whether something is an ergogenic gain, I hope that as we go through these, you keep in mind a few key things that really need to be established when you're evaluating the utility of a new supplement.
The first is, what is the physiological mechanism by which this supplement could possibly improve performance? The second would be, are there studies that don't just show that the physiological mechanisms are in place, but that they also improve some type of athletic performance or multiple types of athletic performance? And then third, if they do, are there any specific recommendations on dosing or usage that can both help avoid maybe uncomfortable side effects or unwanted outcomes from the supplement, but most importantly, ensure that the ergogenic benefits of the supplement are going to be reaped by of the user of the supplement?
So, let's start with the supplement sodium nitrate. Now, that term may not sound familiar to you, but what may be more familiar is the term beetroot juice. And beetroot juice made its way into the sport nutrition world mainly as a supplement that was marketed to improve endurance performance because of its rich content of sodium nitrate. So, why sodium nitrate and why endurance performance? Well, ultimately, it all comes down to when sodium nitrate is reduced into nitrite and then absorbed into its bioavailable form and muscle and tissue known as nitric oxide. That nitric oxide is known to be, first and foremost, a powerful vasodilator. So, it improves our ability to accommodate blood flow in skeletal muscle and deliver oxygen.
And then additionally, nitric oxide has also been found to reduce the oxygen cost of activity. And it does this via a couple of mechanisms. One proven mechanism is that it improves the phosphorylation efficiency. So, if you look at the amount or the ratio of phosphate to oxygen when performing with more nitric oxide, that ratio will be higher, indicating that there's improved phosphorylation efficiency occurring in the mitochondria, and that we're getting a little bit more ATP yield per unit of oxygen that's making it into the mitochondria.
The second way that it's been proposed to reduce the oxygen cost of activity is that it actually has antioxidant properties. And via its antioxidant properties, there are some calcium channels in the sarcoplasmic reticulum that are stimulated by some of the reactive oxygen species that are produced during exercise. And if we think about what that means, well, ultimately, while we know that stimulation of sarcoplasmic reticulum calcium channels is necessary for muscle contractions, we also know that that is an energy-costing process because of the sarcoplasmic reticulum ATPase pumps that must work in order to keep that flow of calcium going in the right direction. So, when these ROS simulations of the SR calcium channels at any given unit of oxygen cost are limited, we are using less energy to facilitate the movement of calcium in and out of the sarcoplasmic reticulum.
And then finally, there have been studies that suggest that nitric oxide may actually enhance the adaptation cellularly to endurance exercise. So, we know that mitochondrial protein synthesis and mitochondrial biogenesis are hallmark adaptations to endurance training, and nitric oxide is actually a simulator of some of the pathways of mitochondrial biogenesis.
Now, if we take a look at studies, given all of these physiological mechanisms by which ultimately be reduced or sodium nitrate supplementation should work to decrease the oxygen cost of activity, that has been shown across a pretty large range of intensities. So, there have been studies that have shown improvements. So, this would be an improvement in economy because we're using less oxygen and less energy to perform the same rate of work. And this has been shown at 50% all the way up to 80% of VO2 max by an average of about one to five percent reduction. So, that doesn't sound like a lot, but if we think about that in the context of endurance exercise performance that goes on for long periods of time, those little bits of savings can make big energetic gains in the long run, especially later on, which can potentially improve performance.
But this has also been shown at higher exercise intensity. So, if we look at studies that have looked at four kilometer and 16 kilometer cycling time trial performance, so much shorter bout of exercise, likely a high percentage performed at lactate threshold or slightly above lactate threshold, it does seem to also improve economy through reducing the oxygen cost to perform at any given some some maximal work rate. So, a pretty wide range of effects from low to high intensity endurance-related exercise.
So, how sure that we take this supplement? Well, first things first, there should be some caution when we look at the benefits because when we look at studies that have been done in highly trained individuals versus more recreationally active or even sedentary individuals, there are benefits, but the benefits seem to be less pronounced, likely because those highly trained athletes have such high-functioning mitochondria and probably really sufficient stores of endogenous nitric oxide without supplementation, that they're already getting a lot of these benefits. But there, they may still get a small benefit from this supplement.
And in order to get any benefit from this supplement, it's typically known. Now, this is not a functional level. So, I think what comes after it is better set: six to eight millimoles of nitrate. Again, what does that mean? Is the effective dose? So, if you're trying to get that much, you can usually get it in about 500 milliliters of a standard beetroot juice, or they do make very concentrated powders such as such as this beetroot sport powder that's shown here, where on average, you can get that amount of nitrate and in 70 milliliters or so, so considerably less. But standard beetroot juice is just fine.
And this is meant to be a pre-exercise supplement, and it does take a fair amount of time it to be digested and absorbed fully. And so, you want to make sure that you take it before about two to three hours. And it seems to work better the more you use it. So, studies that looked at timing have shown that multiple days of supplementation have been more effective than just, you know, here and there acutely giving a single dose, which makes sense if you if you supplement with it chronically, that should lead to greater endo formation than just the sporadically taking the the sodium nitrate every once in a while.
The next ergogenic aid I'd like to look at is beta-alanine. And this is definitely a really widely used supplement. You'll see this show up in a lot of multi-ingredient workout supplements. And beta-alanine is just a non-essential amino acid, which on its own may not do very much. But what it does do is when it's combined with the amino acid histamine, it forms a very important compound known as carnosine. And what this carnosine do? Well, if we think look and we take a look at what carnosine's role in skeletal muscle is, it actually serves as a hydrogen ion buffer.
So, if we think about what happens during exercise, specifically even more high-intensity exercises, more of these hydrogen ions are released from skeletal muscle, and the pH locally in the muscle decreases. Well, this carnosine compound is one of the buffering methods that we have to get rid of some of those hydrogen ions and stabilize pH back to normal levels, so that we can restore muscle function for for subsequent efforts. So, I think that you all can probably guess exactly which types of training beta-alanine supplementation has been suggested to enhance performance.
And if we look at where the majority of this research is focused, the majority of studies support the use of beta-alanine as a ergogenic aid for anything where glycolysis is running at high rates, and lactic acid production and associated it has associated hydrogen ion accumulation from the dissociation of lactic acid is a hallmark of that activity. And so, we really see the benefits of this particular supplement because its mechanism is to clear hydrogen ions out from previous bouts. So, in short periods of time, we start to see the pronounced effects of beta-alanine supplementation in repeated bouts of high-intensity exercise, types of exercise where acidosis is the primary cause of fatigue.
So, there a majority of studies have shown effects for things like repeated sets of resistance exercise, but also things like aerobic exercises that typically are held slightly above the lactate threshold, so like middle-distance running or an 800-meter runner would be a really good example of this. You could also think of soccer players who play positions where they are intermittently going between moderate intensity jogging and periods of high-intensity running into sprinting. So, these types of exercise have been shown to benefit from this particular hydrogen ion buffer known as beta-alanine.
But as you may have guessed, during more prolonged endurance exercises where acidosis and hydrogen ion accumulation are generally not to be considered to be the primary causes of fatigue, there really any studies to support the use of beta-alanine for improving those types of performance. So, if you're looking to get a benefit from beta-alanine supplementation for the types of performance discussed, the studies would suggest that the most effective dosages are between 3.2 and 6.4 grams per day ingested over smaller doses, so not in one bolus dose. It takes a little time for this to to potentially build up and to increase muscle carnosine levels, so it's not the type of supplement that you need to really time with regards to exercise all that much, as long as you're getting the recommended effective dose and ingesting it kind of equally over several smaller doses.
And one of the reasons that you don't want to do that is that there are side effects of bolus doses of this of this particular supplement, and the most commonly reported one is that it causes allergic reactions in the skin with flushing and tingling sensations.
In the next ergogenic aid I'd like to discuss is beta-hydroxy-beta-ethylbutyrate, or HMB for short. And this is actually a metabolite of the amino acid leucine. We've talked a lot about we've seen being a potent simulator of the mTOR pathway, and one of the reasons that we've seen is a potent simulator of the mTOR pathway is because the mTOR pathway is actually directly stimulated by leucine's metabolites, beta-hydroxy-beta-methylbutyrate. And about 5% of leucine is converted to beta-hydroxy-methylbutyrate via transamination and via the activity of the enzyme KIC oxygenase. And it's really potent the effects of beta-hydroxy-methylbutyrate on the mTOR pathway, so it stimulates protein synthesis and inhibits protein breakdown, and it does so via that transcription factor that we discussed with relation to leucine in the mTOR pathway.
So, as I suggested, only about 5% of leucine is actually converted into beta-hydroxy-methylbutyrate. And so, when we look at the studies that have shown performance benefits of beta-hydroxy-methylbutyrate, one of the things that we'll want to consider is that the doses of beta-hydroxy-methylbutyrate given shown to be effective are somewhere between one and a half and three grams. So, in order to get that from just leucine, you would have to ingest about 60 grams of leucine. So, that's one of the reasons why I think some when your first questions might be, well, if this is just a metabolite of the of the amino acid leucine, couldn't I just eat more leucine or supplement with more leucine and get more beta-hydroxy-methylbutyrate? The answer is yes, but you would have to eat quite a lot of leucine to get the effective dose.
So, let's think now about if this is potentially going to influence strength and lean body mass. It seems pretty obvious that the majority of studies would be looking at resistance training. And if we look at studies that have examined the effects of beta-hydroxy-methylate supplementation on body mass, lean body mass in particular, as well as muscular strength, this particular example, we see a group of resistance-trained athletes supplementing with two different doses of beta-hydroxy-methylate, some 1.5 grams and 3 grams, and this was over a three-week period. And they looked at both their lean body mass as well as their total lower body strength by adding together their one-repetition maximum from several large body lower body lifts.
And so, one of the things that has been shown the most consistently is that there are some increases in strength across studies that are noted from beta-hydroxy-methylate supplementation. And then studies are kind of a clinical from studies do show an increase in lean body mass. Some studies don't. This study didn't show an accrual of lean body mass. However, I think we have to look at the fact that this was from a study that will get three weeks of supplementation, and typically that can be a pretty short time to observe hypertrophy and measurable changes in mass.
So, when we look at studies and resistance athletes that has gone longer periods of time, say like eight weeks, 12 weeks, 16 weeks, you usually do see significant changes in lean body mass as well. And so, if we look at these studies, one of the things that has been shown is that there is a small benefit to supplementing at 3 grams versus 1.5 grams, but it's generally recommended that those 3 grams are taken over the course of three servings throughout the day. And this is really key because if we look at most of the data hydroxymethylbutyrate substances on the market, they actually contain significantly less than this amount of HMB.
So, I have referenced this before in the course, but one of the things in the supplement industry that is definitely a problem is that they're not required to put at least the proven effective dose in these supplements. So, while they might be giving you something that in theory works, they may be giving you significantly less than, or in some cases, significantly more than what you need to get that benefit.
The next ergogenic gain we'll discuss is the derivative amino acid carnitine. And carnitine is found in really high concentrations in skeletal muscle. It's made naturally, and it's derived from the amino acids lysine and methionine. And most of our carnitine content, about 97, 98 percent, exists inside of skeletal muscle. And it claims to improve endurance performance by increasing fat oxidation, sparing glycogen. So, how does it do that?
Well, one of the reasons that 98% of your carnitine content is found within skeletal muscle is because carnitine plays an extremely important role in getting fatty acids from the cytoplasm. So, once they've actually crossed the sarcolemma of the muscle cell, this is specific to long-chain fatty acids. Medium-chain fatty acids actually don't need this transport mechanism. But those fatty acids, once they're in the cytoplasm, still need to get across the mitochondrial membrane so they can undergo beta-oxidation and subsequent ATP generation and the electron transport chain or phosphorylation in the electron transport chain.
So, in order for that to occur, carnitine is a key compound in this in this transport. And so, carnitine is actually able to cross the mitochondrial membrane into the cytoplasm. So, this would be the outer mitochondrial membrane. And what carnitine is able to do is it picks up fatty acids and forms this fatty acyl carnitine complex via the enzyme carnitine palmitoyltransferase. You know that palmitic acid is one of the most common dietary long-chain fatty acids. And so, that's where part of this name of this enzyme, carnitine palmitoyltransferase, comes from, is that this is the enzyme that when carnitine binds with these long-chain fatty acids, allows it to form this fatty acyl carnitine complex. And that complex is what's able to then go through the mitochondrial membrane.
And once that happens, those fatty acids are now able to be released from that fatty acyl carnitine complex and undergo beta-oxidation. So, when you have higher concentrations of carnitine within the muscle, well, then theoretically, more fatty acids will be transported into the mitochondria, which ultimately may help to spare some of your storage of carbon, your stores of carbohydrates, if you're able to do that at to a greater degree.
And if we look at where we can get carnitine in the diet, it's primarily found in meat products. And many people say that the redder the meat is, the more carnitine content that it has. And we can see that far and away, sheep and lamb and beef seem to be the biggest sources of dietary carnitine. So, these would all be examples of very red meats. We do get some from other sources. I don't think rabbit is a huge portion of most diets, maybe in some places in the United States. But and typically in red meat is where we see the majority of dietary carnitine. So, this is the amount of carnitine that you can get per 100 grams of a serving of each one of these sources of beef.
And so, one of the things that can be challenging in trying to either dietarily and even more challenging with a supplement is to increase muscle carnitine content. And this is due to the fact that, as I mentioned, carnitine exists primarily in two places: muscle, where about 97% of it is, and then the rest of it is in is in blood. And the problem with that is that if 97% of it is in the muscle, well, that means only 3% of it is in the blood. And so, in order to get any extra carnitine that comes from supplementation or carnitine in the diet into the muscle cell, it's working against this really, really unfavorable concentration gradient. So, this makes it difficult to increase muscle carnitine levels above what they are.
And so, this could be part of now, this unfavorable concentration gradient is probably why the early studies on carnitine supplementation and performance, and more importantly, whether or not these could actually increase muscle carnitine concentration, fail to show those effects. And these were pretty large doses of carnitine over a decent amount of time here. And so, this led researchers to start to investigate, well, are there other things that we could do other than just giving more and more carnitine, which doesn't seem to be feasible or possible as a way to increase carnitine concentration to help improve the uptake of this carnitine across the muscle cell in the face of this slowly unfavorable gradient?
And so, studies that have been successful in showing an ergogenic benefit of carnitine have found that it's most effective in increasing muscle carnitine concentrations when it's ingested with carbohydrates. So, in these particular studies, or the one that we're highlighting here, what they did was they had individuals supplement with carnitine for a period of 24 weeks against a control. And the control group was given 80 grams of carbohydrate as the placebo. And then in the experimental condition, that same 80 grams of carbohydrate was given with two grams of carnitine in the form of L-carnitine heart rate supplement.
And what the researchers did find were was that the addition of carbohydrate to the carnitine supplement at a rate that was lower than what they were giving on its own, at about two grams with a pretty substantial amount of carbohydrate, at 24 weeks showed about a 20% increase in muscle carnitine content. So, a pretty long period of supplementation is needed, and you definitely need to ingest carbohydrate along with it.
Now, why does the carbohydrate work? It's thought that the insulin spike from the carbohydrate gets the membrane a little bit more permeable and facilitates the uptake of carnitine. We know that insulin has some pretty potent effects on membrane permeability. So, in the presence of insulin, it seems like more carnitine, when it's ingested with carbohydrate, makes it across the sarcolemma and can then be stored in the muscle.
And when these studies looked at not only, or when this particular study was, so I'm not only an increase in muscle carnitine content, they also saw an improvement in fat oxidation that led to sparing of muscle glycogen during prolonged lower-intensity bouts of exercise, about 50% of VO2 max. And they also had perform higher-intensity exercise, so about 80% of VO2 max, and saw that because they were breaking down less glycogen and up-taking more fat, there were lower lactate accumulations at this percentage, at this relatively high percentage of VO2 max. And that when they gave them a performance test, there was an 11% improvement in their 30-minute workout put. So, some pretty substantial effects of carnitine increasing muscle carnitine content, albeit it is a rather difficult supplementation protocol in that it takes, it can take months because of the unfortunate concentration gradient that you're working against, it can take a long time to actually substantially increase that carnitine content and see these performance benefits.
And the other downside is that it involves relatively large ingestion of carbohydrate. So, if you are trying to watch energy balance and you don't necessarily want to take 80 grams of carbohydrate, which is a lot, with your carnitine supplement, maybe the benefits don't outweigh the negatives of having to ingest the extra energy. But if you can get it in with some of your normal carbohydrates that you're going to ingest in the diet anyway, and you're not as concerned about energy balance, and maybe that's not, that's maybe the benefits outweigh the risks.
So, if you're looking for an ideal dosing strategy, normally about 2 to 3 grams per day taken in one dose. Timing not really of the essence here relative to the exercise session because as you can see, it takes about, it takes several weeks, 24 weeks on average of supplementation to see this particular particular benefit. But taking it in with about 80 to 90 grams of carbohydrate to facilitate the uptake.
Now, caffeine is an ergogenic aid which certainly needs no introduction to most people. And it's most well-known obviously for its central nervous system stimulant or effects. Obviously, there is a wide variety of cognitive uses for caffeine due to its stimulant effects, but also as a result and as a result of a couple of other mechanisms, caffeine has been pretty well demonstrated as an ergogenic aid in the context of human performance.
And if we think about what the mechanisms by which caffeine exerts its ergogenic properties, several mechanisms have been proposed and studied. And the first is due to the feeling of alertness that caffeine gives individuals. And the way that this works is that caffeine is actually very similarly shaped to adenosine. And your brain has adenosine receptors, and when adenosine binds to receptors in the brain, it's associated with feelings of tiredness and initiations of the sleep cycle. And when caffeine, which is somewhere always shaped, binds to those receptors and blocks it, it kind of blunts those feelings of sleepiness and produces an acute feeling of alertness.
This also has metabolic outcomes because adenosine normally inhibits lipolysis. And by inhibiting adenosine, caffeine stimulates lipolysis. And that's just one of the ways in which it does that because the second mechanism by which caffeine may improve performance in certain contexts is through increasing lipolysis through enhancing the release of epinephrine and norepinephrine and its effects on hormone-sensitive lipase, which we've discussed previously. So, hormone-sensitive lipase is key in getting fatty acids from their triglyceride form, and it is stimulated by the release of epinephrine.
And so, some suggested that perhaps this increases fat oxidation and potentially exerts a muscle glycogen sparing effect. And then third, obviously, there are some psychological properties such as enhancements of moods that people also prefer or when taking caffeine. And this is thought to be due to enhancements of either the re-release or the release and/or reuptake of certain neurotransmitters. For one, caffeine has been shown to enhance serotonin reuptake. And well, this is partly in kind of explaining some of the enhancements of mood, but from an exercise perspective, individuals when supplementing with caffeine typically report lower ratings of perceived exertion.
And then finally, caffeine, because of its effect on neurotransmitters, can also cause an increase in the release and flux of calcium into the sarcolemma. And so, ultimately, while caffeine has a lot of psychological benefits and in terms of improving mood and alertness, and also may have some stimulatory effects on fat metabolism, it may also result in more excitable muscle fibers.
So, given all of these potential physiological mechanisms by which caffeine works, you may not be surprised to find that there have been a whole host of different observations across endurance, strength, and power performance, as well as cognitive function in sports or activities that have heavy mental processing components. And this has been shown acutely across a wide range. And if we think about how much caffeine is necessary to get the ergogenic effects, it's variable, but normally about 3 to 9 milligrams per kilogram of body weight in the our previous two exercise will give a performance benefit.
So, if we think about that for a normal-sized or like an average-sized individual, rather, that's a pretty large range. It's anywhere from two. Now, these are standard six-ounce cups of coffee. These are obviously not your large Starbucks cups of coffee, but this is it could be anywhere from two to six cups of coffee, or 210 to 7630 milligrams if you were taking like a caffeine tablet or some other sort of caffeine supplement, which would be equally expected as effective. Studies show that it doesn't seem to matter the caffeine comes from coffee or a caffeine supplement in terms of the ergogenic benefits for athletic performance.
And above this rate of intake, as you can see in the study here depicted to the right, where they looked at the effects of time to exhaustion at about 80% of VO2 max, there really isn't much of a benefit beyond 9 milligrams per kilogram of body weight. And we also see that individuals who are habituated to caffeine or intake caffeine regularly can still get the performance benefit. So, that doesn't seem to go away over time. But one adjustment that does seem to be that seems to be reported is a little bit of tolerance built and having to go up higher into that range of 3 to 9 milligrams per kilogram to get the benefits over time.
So, with a really best approach with this is to start low and test your sensitivity to it because it is really variable. Some individuals are completely insensitive to it, and some individuals are very sensitive to it. And so, what's best to do is to find the minimum amount needed to get performance benefits, but to avoid side effects such as anxiety, jitteriness. And then also, one thing that we definitely would want to make sure of is that we exude some caution with this supplement when exercising in extreme thermic conditions, hyperthermic conditions, because caffeine does have a diuretic property and will enhance some of the fluid volumes and sweating that occurs during exercise.
On to another ergogenic aid which for individuals in this class probably also needs no introduction, and this is creatine, which is obviously a component of phosphocreatine, one of our high-energy phosphates. So, supplementing with creatine has been proposed as a way to increase the amount of phosphocreatine in the muscle, which would have obvious effects on being able to have more of phosphocreatine molecules to donate their phosphates to ADP and reform ATP at relatively high rate.
So, let's take a look at how much creatine we have available in muscle and why supplementation may be an advantageous strategy for enhancing our muscle creatine stores. Creatine is synthesized in the liver as well as in the kidney from the amino acids glycine, arginine, and methionine, as you can see depicted here, before it's released into the blood via those organs. And if we look at the storage of creatine, so this would be creatine that exists as either creatine or that has found the phosphate in the form of phosphocreatine. If we look at the whole body, across both muscle, heart, and brain, so these are the three tissues where we find creatine the most, about 30% of it as a whole exists as phosphocreatine. So, far more is stored as creatine without that phosphate. But if we look specifically in skeletal muscle, about 60 to 70% of the creatine found in skeletal muscle exists as phosphocreatine. And that makes a lot of sense given the role of phosphocreatine in ATP production.
But we also get some creatine from the diet, and it's mostly in red meat and fish. But it takes a fair amount of those particular foods to get even close to the amount of creatine that we excrete on a daily basis. So, we urinate out about 2 grams of creatine each day, and in order to get that much from the diet, you would need to eat about 16 ounces of steak, which is a pretty couple servings of steak, and more steak than a lot of individuals would be comfortable eating. So, you can see why if we're trying to enhance muscle storage of phosphocreatine, supplementation strategies became the go-to rather than continuously trying to eat enough creatine in the diet for practicality purposes.
So, what happens obviously when we give creatine as element? It gives the body more of the raw material to make more phosphocreatine, which is functionally what's going to exert its ergogenic aids in the context of human performance. And we can see here depicted the dietary content of multiple sources of fish and meat. And we can see once again that there are pretty trace amounts of creatine per 100 grams. So, you would have to eat several servings of meat or fish. And then if we start to look at our our vegetarian sources like milk and cranberries, there's very, very small amounts of creatine found in those. So, you would have to eat quite a lot of those foods to get the amount of creatine that you would from a piece of meat or fish or one of the creatine supplements that are available on the market.
And so, this brings us to the idea of creatine loading. So, the idea of supplementing with creatine is to saturate muscle phosphocreatine stores. This has been suggested by the supplement companies as a way to enhance muscle creatine stores dramatically and quickly, and then reduce with a lower phase of lower dose supplementation known as a maintenance phase. So, most products recommend this six-day loading phase, and it varies a little bit depending upon the supplement. But the loading phase usually involves taking in about 20 grams of creatine a day. So, remember, a four-ounce steak only has about a half a gram, and 20 grams a day is a lot. So, most loading patterns would call for it to be ingested in four smaller servings per per day.
And this certainly does seem to be an effective strategy at enhancing phosphocreatine content in muscle to really, really rapidly. So, studies have shown that when loading, the overall whole body creatine content can increase by about 20%, but that about percent of that is stored as phosphocreatine. So, obviously, this is going to have really important effects for the muscle. But at this point, the muscles are usually completely saturated with creatine. So, continuing to ingest at this high dosage of 20 grams per day is it's not going to lead to more enhanced saturation beyond that point.
And so, the maintenance phase that would occur after that initial six, seven-day loading period would involve a half-gram serving of creatine per day. So, the idea being that muscles are saturated at that point, but we still want to provide creatine at around the level at which it's being excreted in the urine each day.
But when we look at a study or studies that have been done, this is one in particular that have looked at phosphocreatine concentrations after 28 days of supplementation. So, with one strategy being to load in the initial six days with this two grams a day maintenance phase, or a pattern of creatine supplementation that skips the loading phase, which would be about 3 grams per day, so a more modest level of intake. We see that although it's undeniable that in the early phases, the loading strategy, the loading strategy very quickly saturates muscles with phosphocreatine, if we look at things just four weeks later, muscle phosphocreatine levels are at about the same. So, really, the loading thing is effective, but it's not really necessary unless you need that increase in phosphocreatine storage to be quick.
So, does creatine work? And so, we could go over study after study after study that suggests that, as you might imagine, for short duration, high-intensity bursts of activity, that creatine improves performance. We certainly see that creatine improves performance for resistance training exercises, but also not just for resistance training exercises, but if we look at something like maximum sprint cycling, so this would be repeated bouts of six seconds of all-out sprints with 30 seconds of rest in between, we can see that in comparison to a placebo, six days of creatine supplementation and group of of already fit trained individuals was enough to maintain a pretty significant significantly less of a drop in work rate across the ten bouts of cycling when given creatine compared to a placebo. So, we could see that their pedaling rate and because the resistance on the bike was fixed, the power rate declined significantly with each bout in the placebo, whereas that decrease with creatine is much, much less. And the reason for that, of course, is because the muscle has a better capacity to build more phospho, rebuild more phosphocreatine during the rest periods. And the same would be true for repeated bouts of resistance training.
Now, the other popular claim is that creatine use will increase muscle mass. And this is partly true. If we look at studies of this is a study of college football players who were engaging in a resistance training program along with sprint and agility training program, and all other aspects of their diet were controlled for, we can see that the individuals who were given creatine significantly increased their body mass, and that the majority of that increase, which was significantly more than it was as a placebo group, was made of fat-free mass.
And if we then look at what accounts for this or how this works, is it because creatine is directly increasing muscle mass? And it's not because creatine is increasing muscle mass, it's because creatine is making individuals stronger. And as a result of getting stronger, they are tolerating heavier loads and increasing their lean mass, which is then also feeding into their increases in strength. So, is there some direct stimulation of like a hypertrophic growth factor that occurs that allows for creatine to to produce these changes in lean mass? No, it's usually because you can tolerate heavier loads when supplementing with creatine, and therefore the mechanical stimulation of growth occurs and then feeds into more of subsequent strength gains.
Sodium bicarbonate is definitely one of the most tested intracellular buffers of hydrogen. And this is a classic undergraduate exercise physiology lab experience that is given in many, many courses and different programs where you'll have an individual ingest baking soda. So, this is a very readily available supplement. You don't necessarily need to have a specific baking soda capsule supplement like the one depicted. You could just use regular baking soda.
And the reason that sodium bicarbonate has been suggested to be an effective buffer of acidosis is because, as you already know, bicarbonate is an important reaction, or the bicarbonate buffering pathway is one of the ways in which hydrogen ions are removed. And so, we'll be familiar with the fact that bicarbonate, the bicarbonate buffering reaction works by making carbonic acid via the bicarbonate anhydrase equation, which can then be broken down into water and carbon dioxide, so that we can see that chemical action depicted here.
Now, as a result, supplementing with sodium bicarbonate has been shown to increase your plasma bicarbonate levels. And therefore, because you have more bicarbonate, you're able to remove more hydrogen ions from the muscle and decrease the acidity and raise the pH. So, this is another, this is another acidotic buffering supplement. And if we look at studies that have investigated the effects of sodium bicarbonate ingestion on exercise performance where acidosis is a limiter, we'll see that during high-intensity exercise in both recreationally active and well-trained people, there is a pretty substantial effect on performance of these types of exercise when ingesting sodium bicarbonate. You can see on the graph depicted to the right, there can be some pretty substantial increases in performance. This is looking at studies across multiple studies in which different doses of sodium bicarbonate were given.
But the issues with sodium bicarbonate for many athletes may outweigh the benefits. And as you might imagine from ingesting sodium bicarbonate, there are some uncomfortable gastrointestinal side effects, especially when the doses of sodium bicarbonate ingested are large. And the reason for this is because if we think back to the bicarbonate buffering system and that pathway, there, the end products are going to be water and carbon dioxide. And that, along with the large amounts of sodium that accompanies sodium bicarbonate and the effects of fluid retention, sodium on fluid retention, there seems to be a large buildup of carbon dioxide and some reactions with hydrochloric acid that tend to cause bloating. Results there also have been some reports of cramping and diarrhea when large amounts of sodium bicarbonate are ingested. So, this can have a benefit, but it also can have some really uncomfortable side effects.
When looking at the amount of sodium bicarbonate needed to improve performance, typically it's about 200 to 300 milligrams per kilogram of body weight. And this has been shown to improve high-intensity exercise performances of around one to ten minutes in duration. So, again, thinking about types of exercise where acidosis is a primary cause of fatigue.
Now, in order to potentially take advantage of this, you would want to take it a couple hours, maybe one to two hours before the exercise. About and absolutely, one of the things that's been shown to reduce the gastrointestinal distress is one, taking it before exercise, so that gives you a little bit of time to maybe eliminate some of that CO2, get rid of some gas and bloating. But also drinking a large amount of water may also help to alleviate some of the some of the gastrointestinal symptoms that are associated with sodium bicarbonate ingestion.
The last supplement I want to take a look at today is medium-chain triglycerides, or MCTs. And these are typically sold as a supplement in oil form, usually harvested from coconut oil. But these are just fatty acids. They're not anywhere near as abundant in the diet. They are present in small quantities in the human diet. And what distinguishes these from long-chain triglycerides like palmitic acid, which are found in large quantities in the human diet, is that these have shorter carbonyl lengths. So, these are usually eight to ten carbons and in terms of how many make up that chain. And as a result, we'll take a look at physiologically why, in terms of thinking about these as a use as an ergogenic aid, they have been suggested to be a more rapidly digesting and absorbed fatty acid that may provide a quickly usable energy source compared to long-chain triglycerides or breaking down stored fatty acids.
So, if we take a look at why this might be the case, we can see that unlike long-chain triglycerides, which ultimately, as we've discussed previously, need to be packaged into chylomicrons and enter circulation via the lymphatic system, well, medium-chain triglycerides, because they're smaller molecules and smaller carbon chains, are actually more able to diffuse through the lumen of the intestine and enter circulation directly through the hepatic portal vein, where they can then go to the liver. So, compared to long-chain triglycerides, this process is much more rapid and doesn't require repackaging and entry and circulation through the lymphatic system before those fatty acids are then taken to the liver.
Now, the other thing that is unique about medium-chain triglycerides is that the fatty acids from these medium-chain triglycerides, so these medium-chain fatty acids, once they enter circulation and then they are delivered to the muscle cells, they are able to enter the mitochondria without the need of carnitine. So, we talked about carnitine as a supplement that potentially can enhance the uptake of long-chain fatty acids because of its involvement with getting fatty acids out of the the cytoplasm or the sarcoplasm of a muscle cell and into the actual mitochondria for beta-oxidation. Well, medium-chain fatty acids actually don't require this carnitine compound. So, they're actually able to go and diffuse into the circle into the sarcoplasm and then into the mitochondria through the mitochondrial membrane without the need for carnitine.
So, the question really then becomes, if these medium-chain triglycerides are easily absorbed and are able to enter the mitochondria easily, can they contribute significantly as a fuel source during exercise? And so, as you might expect, the use of medium-chain triglycerides as an ergogenic aid is usually investigated in the context of types of performance where fatty acid oxidation can reach peak rates and contribute a significant amount to energy expenditure. And so, we take a look at a study done by you can drop in well-trained athletes that were exercising for three hours at about 57% of their VO2 max, so prolonged endurance exercise. They looked at the comparison in a randomized crossover design of having individuals consume either a carbohydrate-only solution, a carbohydrate and medium-chain triglyceride solution, so those two solutions would be isocaloric, they each had the same amount of energy in them with about 30 grams of MCT oil and the rest of carbohydrates, so carbohydrate was around 60 grams per hour, so around the peak rate of oxidation, and then a medium-chain triglyceride only solution containing the same amount of medium-chain triglycerides, about 30 grams, with no carbohydrate. So, this would be significantly less energy.
And if we look at the findings, we can see that if we look at the three conditions and the contributions of these fuel sources to overall energy expenditure, they were rather limited in terms.
Of they looked at tracer methods, so they were able to tell how many or how much carbohydrate was being oxidized, how much that was being oxidized total, and then how much of fatty acids that were being oxidized were coming from the medium chain triglycerides that were ingested. And so they found a small contribution of carbohydrate and medium chain triglycerides when ingested alone, as well as with carbohydrate, of between about three to seven percent of total energy expenditure.
And specifically, the researchers also looked at specific timeframes and looked at oxidation at different time points during a 180-minute bout of exercise. And they found that the oxidation of the medium chain triglycerides across the two conditions was highest during the last hour of exercise. And this seems to make some sense because if we think about what might have happened during that last hour of exercise, muscle glycogen levels were most likely at their lowest during this time point. And we know that depletion of glycogen will increase the oxidation of fatty acids. And we saw in this particular trial that the oxidation of medium chain fatty acids was highest during this last hour when glycogen stores were most likely the most depleted.
Now, this is a small contribution to total energy expenditure. And the limits to this are that the GI tract has trouble tolerating more than about 30 grams of medium chain triglycerides at a time. So in order to get these limited benefits, you need to have at least 30 grams of ingestion. And it seems to be a fuel source during times when carbohydrate availability might be challenged. So in comparison, when we look at studies that have both the effects of MCTs on performance, while they may make a small contribution to energy expenditure, if we're thinking about their supplementation, they actually don't seem to provide much of an extra benefit compared to carbohydrate. So when we look at studies of performance of endurance exercise like time to exhaustion and compare it to carbohydrate, there isn't a clear performance benefit. So they can provide limited amounts of energy expenditure, especially during times when carbohydrate availability is challenged, but they don't seem to outperform supplementing with exogenous carbohydrates.
So I want to leave you with this one last thought here on nutritional supplementation for ergogenic aids. And this is kind of a series of questions that I think are necessary for you, individually, to ask yourselves when making the determination to use or not use a supplement. And the first thing that I think that you want to think about, first, I want to point out that we've investigated ergogenic aids in which there is substantial evidence to make some sort of claim about whether or not they actually are ergogenic. And this is not an all-encompassing list of all of the supplement research that has been done. There are many, many other supplements on the market, many with emerging bodies of evidence that are being tested. And so I think it's important to be able to look at the evidence and make decisions about the utilization of supplements.
And the first question that I hope that you always ask yourself is, is there evidence that the supplement works specifically for your specific sport or event or the type of training that you're doing? And if the answer to that question is no, then there's no reason to use the supplement. If the answer to that question is yes, you may begin to ask yourself some other key questions, like, for example, are there any negative effects? Is it potentially harmful to health or is it harmful to performance?
Something else that I think is important to understand is whether you can get the whether you can get adequate intakes of this compound from food. The example of creatine is a good one. While creatine is available in food sources, you would have to eat a lot of meat in order to get, let's say that you were interested in loading creatine, in order to get the 20 grams over that six-day cycle, you would have to eat quite a lot of meat to get 20 grams, and more than most individuals should eat or be comfortable with. So we wouldn't necessarily want to recommend people eating 10 kilograms of meat per day in order to get this level of creatine. So those are the types of things that you want to ask yourself, can I get this from food, and is it a reasonable way to get it? And if not, then supplementation is likely a good option.
The other thing that is really important to consider is whether the substance is banned. And the list of banned substances for athletes, specifically in competitive arenas, is going to be is going to be dependent upon the governing organization. So being familiar with what the banned substances are and investigating and really critically analyzing a supplement's ingredient labels to make sure that it doesn't have any banned substances. With respect to like college athletics, many supplement companies will put a stamp on the certain supplements that state that there are no NCAA banned substances, but that's not the case for a lot of supplements. So it's very important to check and make sure that the supplements that you're using are not banned by any competitive organizations that you may be a part of.
And the other, the last thing that I think is always important to consider is, is it worth the cost? So many of these supplements are very, very expensive. And you really need to weigh the benefits of, is there a limited potential for ergogenic aid? Can I get this ergogenic aid through other mechanisms that aren't supplementation? And if there are possible benefits to the supplement, is there a more cost-effective way to to get that level of supplementation without buying a super expensive designer supplement? So all of these are considerations that you may want to make when making the decision of whether to use supplements or recommend supplements as ergogenic aids.