Is Creatine Good for Brain Health amd Physical Performance?

Yes, creatine is indeed good for brain health and physical performance. Even for non-athletes.

This week, I had the pleasure of attending a seminar with the eminent Professor Eric Rawson, a leading voice within the exercise and nutrition science field, particularly renowned for his expertise on creatine. Creatine, a compound predominantly found in our muscles and brain, is often discussed in relation to athletic performance. However, this episode is not just for those seeking to enhance their physical prowess but also for anyone with an interest in brain health and cognition.

It’s a real honor to delve into the topic of creatine, having followed Professor Rawson’s work for many years. The opportunity to explore his insights is truly exciting. We shared a light-hearted moment reflecting on the unique world of Twitter, a platform that, despite its mix of positive and negative aspects, can be a rich source of learning and connection when navigated thoughtfully. Twitter has indeed been instrumental in connecting with experts and fostering educational exchanges, provided one can steer clear of the less savory interactions for the sake of one’s sanity.

To provide some context, it’s fascinating to consider the history of creatine research, which dates back to the 1800s. This long-standing curiosity about creatine has led to numerous seminal studies that have established it as a household name and sparked further investigation into its properties and benefits.

The first paper on the discovery of creatine that I came across was published in 1832, marking nearly two centuries of scientific inquiry into this compound. Creatine was a hot topic in the 19th and early 20th centuries, with journals like the Journal of Biological Chemistry dedicating a significant portion of their publications to it. What’s remarkable is that there was a century’s worth of research on creatine before the discovery of ATP and the creatine kinase reaction, which are central to understanding creatine’s role in muscle metabolism. This historical perspective sets the stage for a deeper appreciation of how far we’ve come in our understanding of creatine and its impact on both physical and cognitive health.

The understanding of different muscles and the degradation of creatine was somewhat limited until the discovery of ATP, which was a significant milestone in biochemistry. What’s also fascinating is that the great chemist Justus von Liebig marketed an extract of meat supplements as early as 1847, which was essentially a high creatine supplement. Moving forward to the early 1920s, the first human supplementation study that I’m aware of took place. At that time, muscle biopsies weren’t an option, but researchers could measure creatine output in the urine. Typically, there’s no creatine in the urine, but the two authors of the study, who appeared to be the research volunteers themselves, loaded themselves with creatine and found that not all of it was recovered in the urine, indicating that the supplement was being retained in the body. This paper is now a hundred years old, and it’s remarkable how much work was done without modern technologies.

Then, in the 1960s, the muscle biopsy technique was perfected and gained popularity. This was the first time we could really understand what was happening to things like muscle glycogen and muscle creatine as a consequence of exercise and dietary manipulations. During the 60s and 70s, a lot of research focused on carbohydrate dietary manipulation, exercise tests, and muscle biopsies. However, no significant work in the creatine space was done until 1992, which marked the modern start of creatine supplementation. The seminal paper by Roger Harris, Karen Söderlund, and Eric Hultman was a descriptive study that fed people creatine and measured what happened to their blood creatine and muscle creatine. From this study, we learned that oral creatine supplementation can increase muscle creatine in humans. We also discovered that exercise augments the response to supplementation and that individuals with low baseline creatine levels have the largest response, while those with naturally high muscle creatine have a smaller response. This single paper opened the floodgates for further research.

I’m particularly interested in the idea of baseline creatine levels and how they might differ between individuals, such as vegetarians versus omnivores, who potentially have different baseline levels and may experience varying effects from supplementation. Creatine, as an ergogenic compound, is perhaps the most studied out there, likely due to the reasons I’ve described, including the ability for oral creatine to be effectively utilized by the body.

Understanding how compounds interact with the human body is a fascinating aspect of science, particularly when we consider their journey through the bloodstream and their ultimate destination within our muscles. This process may seem commonplace for various substances, but it’s actually quite unique. As educators, we emphasize the importance of a compound’s ability to reach its intended target. Theoretically, we can predict the effects of a compound if it successfully enters the mitochondria or skeletal muscle and withstands the digestive process. However, the reality is that most compounds don’t make it that far.

The discovery of an inexpensive, widely available supplement that could survive digestion and reach skeletal muscle was a groundbreaking moment. This wasn’t just any supplement; it was a nutrient commonly consumed in people’s diets, making it even more significant. The ability to enhance skeletal muscle with oral creatine supplementation, achieving an average increase of about 20%, was a major advancement.

Interestingly, before the scientific community had fully embraced this finding, athletes and coaches were already ahead of the curve. They had been experimenting with creatine supplementation since the 1980s, if not earlier. By the time of the 1992 Olympics, the efficacy of creatine was becoming more widely recognized, as evidenced by two gold medalists in track who openly admitted to using creatine supplements. This was a clear indication that athletes were exploring and benefiting from creatine long before it became a staple in sports science research.

The use of supplements, particularly among elite professional athletes, often sparks controversy, especially when they prove to be effective. Take caffeine, for example. It’s the most commonly consumed drug in the world, and it’s known to enhance endurance performance, as well as strength and power. The ergogenic benefits of caffeine are well-documented across various scenarios. Yet, the debate around performance-enhancing substances is complex. How can one ban a substance like caffeine that is so ubiquitous and, by all accounts, safe?

This dilemma extends to other nutrients that are part of an omnivorous diet. Banning a nutrient seems impractical, especially when considering that elements like calcium also offer benefits to athletes. The discussions around these topics are ongoing, as the sports world grapples with the ethical implications of supplement use and the quest for fair competition.

Creatine is an interesting compound for a variety of reasons. One aspect to consider is that some creatine comes through the diet, depending on what you eat, and your body also produces it. There’s quite a lot of research suggesting that what is adequate for creatine levels may be different from what is optimal. It’s worth exploring the nature of creatine, how it is synthesized in the body, and how the body utilizes it.

On average, for the general population, normal creatine turnover is about two grams per day. We expect one gram per day to come from exogenous sources, such as the diet, and one gram per day from endogenous production. Creatine is produced from a group of amino acids in the liver, pancreas, and kidneys. What makes creatine supplementation so beneficial is the complete separation between the sites of synthesis and utilization. About 95% of the body’s creatine is stored in skeletal muscles, where it’s used to produce ATP or energy during times of very high energy demand. However, creatine isn’t made in skeletal muscles; it’s manufactured in the liver, pancreas, and kidneys. Skeletal muscle readily takes up creatine, not only the creatine produced in other parts of the body but also the creatine that’s ingested with the diet. Most of the remaining 5% of creatine is stored in the brain.

Regarding whether the compound is considered essential or non-essential, which are terms often used to describe whether one needs it in the diet or not, the typical person endogenously produces about one gram a day, and another gram comes through the diet. The question of whether this is a non-essential nutrient and whether the body will produce enough for adequacy is a great one. It’s a topic that not many people are ready to discuss or have even probed, likely due to its complexity and the nuances involved in understanding the body’s needs and the role of diet and supplementation.

The way to frame it is by understanding that there is a wide range of what is considered normal muscle creatine values. When muscle creatine is low, it doesn’t necessarily indicate impairment. However, there are very rare genetic disorders related to creatine transport or synthesis, which occur in children and have devastating consequences. These children are very sick, and the only way to rescue them is with creatine supplements. This is an extreme example, but it illustrates that there’s a spectrum of what’s considered normal or adequate, and on the other end, severe disease.

Nutrition is evolving from being solely the study of deficiency diseases. We’re in a phase of questioning whether there’s a difference between preventing a deficiency and achieving optimal health. However, not many researchers are examining this thoroughly. The question arises: if you don’t have a genetic defect that drastically reduces your brain creatine levels and causes severe illness, will you benefit from purposefully adding creatine to your diet? Even this question is simplistic.

A recent study using the NHANES dataset, which is quite extensive, revealed that around 40% of Americans aren’t getting enough creatine based on the old perspective of one gram produced endogenously and one gram consumed exogenously. Most people aren’t getting enough creatine in their diet, but does this mean they’re deficient? Or does it mean their health is impacted? That’s a significant question.

Some researchers are advocating for creatine to be reclassified as conditionally essential, which seems fair. It’s not just about creatine itself; it’s about the building blocks. Dietary methionine and glycine, or their levels in the body, are essential for synthesizing creatine. Methionine, in particular, is an amino acid that’s known to be less abundant in certain plant foods, and food combining usually addresses this, but it complicates studying creatine on a population level. It’s not just about having enough creatine; it’s about having enough precursors for the synthesis of creatine. This makes the whole subject much more complex.

Listening to this, it’s super interesting to think about the role genetics play in our body’s production of creatine. It’s intriguing to consider that there might be various genetic polymorphisms affecting this, and that individuals likely fall on a spectrum of creatine production. Some might produce less than others, but it’s not a matter of producing none at all.

Now, one might wonder if there’s a routine laboratory test or a way to objectively quantify creatine levels. Unfortunately, the answer is a resounding no. The relationship between skeletal muscle creatine and plasma creatine isn’t straightforward enough to use plasma creatine as a proxy marker for muscle creatine. A simple blood test won’t suffice. If you were to ask for a blood creatine test at a medical center, you’d likely be met with confusion, as they’d assume you meant creatinine, which is the breakdown product of creatine. Most labs wouldn’t even have the capability to perform such a test; it’s not standard.

To accurately measure muscle creatine levels, you’d need specialized techniques like MRI spectroscopy, which measures concentrations rather than producing images, or a muscle biopsy. It’s quite fascinating, especially when you consider how responsive the carbohydrate system is to various factors, such as dietary changes or exercise, which can increase the muscles’ ability to synthesize glycogen. Creatine metabolism, however, operates differently.

Sharing a personal anecdote, I’ve never been one for long endurance activities. I’m more of a ’30 seconds or less’ type of person. My life has revolved around sprinting and weightlifting, focusing on strength and power. Despite consuming a fair amount of high-creatine foods, when my muscle creatine was measured, I had some of the lowest levels in the entire study. This resonated with my own experiences, as I had experimented with creatine supplements and noticed a significant response. My performance in the weight room improved, and I gained weight. Although my faculty in graduate school were skeptical, I was convinced that the supplements were particularly effective for me.

After undergoing an MRI, it was revealed that my muscle phosphocreatine levels were incredibly low, which was surprising given my lifetime consumption of high-creatine foods and my consistent sprinting exercises. This finding was particularly intriguing because, according to research, the creatine phosphocreatine energy system doesn’t seem to respond to stressful exercises like sprints, which are supposed to specifically stress this system. It appears that if you train like a marathon runner, you’ll see metabolic adaptations concerning fat and carbohydrate metabolism. However, if you train like a sprinter, it doesn’t seem to affect the phosphocreatine levels you’re born with. Fortunately, it’s possible to supplement these levels.

In the realm of nutrition and health, you often come across the term “hyper-responder.” Reflecting on my personal experience, I’ve realized that this concept is particularly relevant to creatine supplementation. We’re talking about skeletal muscle here, not brain metabolism. There’s a clear relationship in skeletal muscle where those with the lowest muscle creatine levels experience the largest increase in response to supplementation. However, everyone experiences an increase to some degree, whether it’s small, medium, or large. I like to use the gas tank analogy with my students: if your tank is full, you can only top it off so much, but if it’s half empty, you can add a lot more.

There are low responders, medium responders, and high responders, but everyone is a responder to some extent. You can augment this response by combining creatine supplementation with carbohydrate and protein, which seems to stimulate muscle creatine uptake more effectively, similar to how exercise does. There’s a very clear relationship in the muscles between the starting point and the response to supplementation.

When considering the potential for a greater magnitude of benefit through supplementation, it’s natural to wonder about the baseline differences in creatine stores between different diets, such as those of vegetarians versus typical omnivores. Unfortunately, there are no exact numbers to quantify these differences. Like many biological measurements of interest, such as cholesterol and calcium levels, creatine also falls within a range. It’s likely that the variation in muscle creatine levels is part of a spectrum, and while we can’t pinpoint exact figures, we can acknowledge that there is a range of natural creatine levels in individuals.

It’s often overlooked, but the creatine levels in vegetarians are significantly lower than those in meat-eaters. This is something that hasn’t been given the attention it deserves. There are a few studies that have either measured vegetarians or converted people to a vegetarian diet and observed a rapid decrease in muscle creatine. Blood creatine is about 60% lower in vegetarians, and muscle creatine is, on average, around 20% lower. Some studies suggest a 15% decrease, while others indicate a reduction closer to 25% or 27%. Taking an average, we could say that vegetarians have 20% lower baseline muscle creatine and perhaps 60% lower blood creatine. These figures provide a good estimate for the creatine levels in non-meat eaters.

Considering these averages, it’s reasonable to suggest that vegetarians might benefit more from creatine supplementation than omnivores due to their lower baseline levels. Although the research on this topic is not as extensive as other areas, the evidence indicates that vegetarians typically experience a greater increase in muscle creatine from supplementation. While omnivores might see a 20% increase, vegetarians often have much higher gains, sometimes 40%, 50%, or even more. Therefore, we can expect vegetarians to have a higher increase in tissue levels and, depending on their sport performance, a larger ergogenic effect due to starting from a lower baseline.

The question of whether it’s possible to consume enough creatine through diet alone is intriguing. In theory, if you’re not suffering from a creatine deficiency disease and you’re not symptomatic, you might be considered fine within the broad spectrum of what’s deemed normal and healthy. However, this raises a deeper question about nutrition: Is health merely the absence of a deficiency-related disease, or is it something more optimal? This is a significant consideration, especially for specific groups such as vegetarians, older adults, individuals with certain neuromuscular diseases, sarcopenia, and certain types of depression. The optimal amount of muscle creatine might be achievable through diet alone for some, but for others, especially those with lower starting levels, supplementation could be a key factor in reaching what is considered optimal for health and performance.

Creatine responsiveness varies among individuals, and there are cases where patients experience reductions in brain creatine. It’s a challenging question to address. From the data we have, it seems that the general population may not be receiving even the minimal amount of creatine they need, which is a concern that hasn’t been widely discussed. This raises the question of whether we should be focusing on creatine intake as we do with other nutrients like calcium. We know that people can obtain calcium through their diet, but the reality is that many do not. So, the issue becomes how to encourage increased consumption to meet these nutritional needs.

When it comes to creatine, the situation is complicated by the fact that it’s synthesized from amino acids, which are the building blocks of proteins. Some vegetarian diets may lack one or two of the essential amino acids involved in creatine synthesis, which is an important consideration.

Discussing the practical aspects of creatine supplementation and dietary intake is crucial. There’s a difference between what’s theoretically possible and what’s realistic and practical in everyday life. When we consider performance enhancement, it’s important to understand the role of creatine at the cellular level, particularly in muscle cells.

Creatine plays a pivotal role in energy production. All macronutrients—carbohydrates, fats, and proteins—must be converted into adenosine triphosphate (ATP) to contribute to this process. ATP is the only molecule that can initiate muscle contraction by fitting onto the myosin head within a muscle cell. Our bodies have a small reserve of ATP, and we have systems in place to replenish it during exercise. We can metabolize fats and carbohydrates to generate ATP, and we also have a store of phosphocreatine in our muscles.

When ATP is broken down during muscle contraction, it must be quickly replenished. The removal of a phosphate group from ATP requires a new phosphate to replace it, which is where phosphocreatine, also known as creatine phosphate, comes into play. This is how creatine contributes to enhanced power, strength, and resistance to fatigue in muscle cells.

In the realm of athletic performance, what’s being explored is the enhancement of the creatine phosphate, or phosphocreatine pool, within the muscles. Consider the scenario where one attempts to sprint a hundred meters at full speed. Relying solely on ATP stored in the muscles wouldn’t suffice; the muscles would be incapable of contracting for the entire distance due to a rapid depletion of fuel. This is where the backup system, phosphocreatine, plays a critical role by donating its phosphate to the chemical reaction, allowing muscle contractions to continue.

The breakdown of phosphocreatine is astoundingly swift. Although it’s a limited resource, its response is instantaneous. This energy system is what enables us to perform ten seconds of maximal sprinting, and it significantly contributes to longer sprints, up to 20 or 30 seconds. This has clear implications for sports like football or rugby, which involve intermittent bouts of sprinting, and it’s also relevant to high-intensity exercises found in events like the Tour de France, where cyclists sprint for the last 30 seconds to the finish line in every stage.

There’s a wealth of evidence, from hundreds of studies, indicating that muscle loading with creatine through supplementation, coupled with challenges of 30 seconds or less of maximal, intense exercise, can enhance performance. Furthermore, studies have shown that embedding sprints into a long endurance ride or at the end of an endurance challenge can also produce an ergogenic effect. This illustrates the potential benefits of creatine for a wide spectrum of athletes, not just the 100-meter sprinters.

When considering endurance exercise and creatine, the conversation often turns to supplementation protocols. The consensus from research suggests that increasing muscle creatine content before the athletic event is most beneficial. There are few studies on the effects of pre-exercise or during-exercise creatine ingestion. Once muscles are saturated with creatine, they maintain those levels for weeks. This is in stark contrast to muscle glycogen, which depletes during a bike ride, for example, and doesn’t replenish until carbohydrates are consumed to refill the tank.

Phosphocreatine, on the other hand, declines during intense exercise but then resynthesizes back to baseline within about three to four minutes. The question of why it would be beneficial during exercise remains, as the advantages of creatine seem to be maximized when muscles are preloaded with it, providing a reservoir of energy that can be rapidly mobilized during short, intense bouts of activity.

Reflecting on the cognitive effects of creatine, I’ve come to understand its significance beyond physical performance. Some athletes I know take creatine daily, prior to their athletic endeavors, and they’ve reported a noticeable improvement in mental clarity. However, the primary goal is often to ‘fill up the tank’ before engaging in strenuous activity, such as cycling.

The concept of replenishing creatine stores post-exercise has been a topic of interest, and indeed, there is scientific validity to this practice. Muscle creatine uptake is insulin-mediated, meaning that it can be enhanced in a couple of ways. While injecting insulin is an option, it’s a dangerous one and certainly not recommended. A much safer and effective method is to consume a well-balanced meal. Carbohydrate and protein combinations, which athletes typically consume after training, can induce a significant hyperinsulinemic response, thereby augmenting muscle creatine uptake.

Exercise itself has insulin-like effects, which can also facilitate creatine uptake. Therefore, if one is to take creatine once a day, the post-exercise period seems to be the most opportune time. There’s no urgency to consume it immediately after exercise, such as in the parking lot or locker room. It’s perfectly fine to wait until you can have a proper meal at home. Some athletes prefer to include creatine as part of their post-exercise snack, which might be a carbohydrate-protein beverage consumed before they shower or settle down for a meal.

The post-exercise window is ideal for creatine intake, but not necessarily immediate. Individuals living with diabetes who require insulin may also find this timing aligns well with their meal schedules. In reality, we may have overcomplicated the process. Muscle creatine uptake can be enhanced simply by eating a candy bar, which triggers a significant hyperinsulinemic response. The debate over the ideal carbohydrate is somewhat moot; the difference between fructose and glucose is less critical than once thought. Simply eating and taking creatine concurrently can be quite effective.

When considering the breadth of research, including hundreds of studies on various types of performance, one might wonder about the magnitude of benefit creatine supplementation can offer. This is a great question and one that underscores the importance of understanding how these effects translate into tangible improvements for athletes and individuals seeking cognitive clarity.

Quantifying the impact of performance enhancements is incredibly challenging due to the variety of performances we’re considering. For instance, we might be talking about repeated vertical jumps, bench press repetitions, a 30-second cycling sprint, or even a 10-second burst. The time domain varies significantly, and when you introduce activities like swimming, you encounter a completely different set of effects.

The impact of certain nutrients on performance is not large, and rightly so. We’re discussing a naturally occurring nutrient that our bodies already store in abundance. We shouldn’t expect it to have drug-like effects, and indeed, it doesn’t. However, the effects it does have, say on the order of four or five percent, can be likened to the response one might get from caffeine or a few other dietary supplements known to enhance performance. While not a large effect, it is practically very significant.

Consider a five percent improvement in a 100-meter sprint in track and field or a swimming event. Athletes win and lose by hundredths of a second, so for elite competitors, even a marginal gain is crucial. But let’s shift our perspective to an older adult dealing with physical frailty. If this nutrient helps them ascend stairs more safely and powerfully, or improves their activities of daily living, then it’s hardly a minor effect.

For the average person, creatine shines brightest in the weight room. There’s a distinction between a sports performance aid and a training aid. In high-intensity exercise routines, like those involving squats with rest intervals, creatine is ideal. It enhances performance in the weight room, which can translate into better athletic performance or an improved quality of life.

I’ve personally been taking five grams a day of creatine monohydrate for as long as I can remember. We can delve into the specifics of creatine types and whether this dosage is well supported by evidence shortly. But considering creatine’s role in replenishing ATP, crucial for energy production and performance, it’s clear why this supplement is valued. It’s a bit of a silly question, but one might wonder, why not just take an ATP supplement directly? Well, the body’s mechanisms are more complex, and it’s not just about the raw materials but how they’re utilized and stored.

The concept of taking an oral form of ATP to bypass creatine is intriguing, but the reality is that it’s supposed to get destroyed by digestion. I believe it will indeed get destroyed by digestion, and any remnants that don’t will unfortunately not increase the body’s ATP stores. While there may be a one-off study suggesting that ATP supplements produce a significant ergogenic effect, these findings are often not reproducible. They don’t build upon the robust body of evidence we see with creatine, where replication comes in the form of hundreds of studies. The idea of eating ATP and expecting it to survive digestion is something I’m skeptical about, despite some curious findings in the past.

Now, shifting focus to creatine supplementation in older adults, particularly in relation to sarcopenia and muscle loss, which can profoundly affect quality of life. There’s a substantial body of literature on this topic. In fact, we were involved with the original studies back in the mid-90s. It struck us that if we’re considering creatine and protein to enhance the performance of the biggest, fastest, and strongest individuals, why not apply the same logic to older adults? They’ve already experienced some muscle loss, strength reduction, and decreased muscle endurance and mass.

We began administering creatine to older adults in the mid-90s to observe its ergogenic effects. We noticed improvements in muscle endurance and reductions in muscle fatigue. Subsequently, other researchers incorporated creatine into long-term resistance training programs for older adults, and the results have been very positive. There are now systematic reviews and meta-analyses focused solely on the effects of creatine on exercise performance and muscle mass in the older population, and it’s proven to be very effective.

One question that arises is whether older adults have decreased muscle creatine levels as a result of aging. This is difficult to determine because all human aging research is confounded by decreased levels of physical activity. The endocrine environment is changing, with reductions in hormones like testosterone and growth hormone, coupled with type 2 fiber atrophy and decreased physical activity. It’s challenging to pinpoint what exactly is driving an age-related reduction in muscle creatine. Some studies do show a decrease, but it’s not consistent across the board. It’s possible that aging could bring older adults’ muscle creatine levels down to those of a vegetarian, but the evidence is not conclusive.

In considering the nuances of muscle creatine levels and the potential benefits of supplementation, it’s clear that there exists a subset of individuals with what could be described as a clinically deficient level of muscle creatine. These individuals don’t necessarily have a known impairment, but their reduced muscle creatine levels suggest they could significantly benefit from creatine supplementation.

The relationship between exercise, particularly resistance training, and the body’s endogenous production of creatine is intriguing. When you engage in more resistance training and build more muscle, one might assume the body would naturally produce more creatine. However, evidence suggests otherwise. Biopsy studies of sprint-trained athletes and multiple resistance training studies, where the placebo group did not show a spontaneous increase in muscle creatine, provide compelling insights. I always find it informative to examine the placebo group in these studies to understand the baseline effects.

The impact of physical activity on muscle creatine is especially pertinent when considering the elderly population. Consistently, we observe that extremely low levels of physical activity, such as immobilization, can lead to significant reductions in muscle creatine—up to a 25% reduction if an arm or leg is immobilized. This could be seen as a model for aging in some individuals, but not all older adults experience these effects. While extremely high physical activity doesn’t appear to increase muscle creatine, the opposite—extremely low physical activity—certainly seems to decrease it.

When it comes to the dosages for creatine supplementation, whether for an older athlete or older adults in general, the dosing protocol remains consistent across different populations. The process is akin to filling up a gas tank. There are two main approaches: if one is in a hurry, a loading phase of about 20 grams per day for five days can quickly supersaturate the muscles with creatine. This dosage applies to most individuals, as it’s rare to encounter someone with a body composition that would necessitate a higher intake. Alternatively, a more gradual approach involves taking somewhere between 3 to 5 grams per day for about a month to achieve the same level of muscle saturation. It’s important to note that there’s a ceiling to how much creatine the muscles can hold; they cannot indefinitely increase their creatine content.

Choosing between the rapid loading phase and the gradual approach depends on the individual’s circumstances. For instance, when working with a patient population like frail elders, it’s crucial to consider the potential for gastrointestinal upset. Although there’s no strong evidence that creatine causes such issues, there are occasional reports of discomfort, sometimes even in placebo groups. Therefore, the choice of supplementation protocol should be tailored to the individual’s needs and tolerance.

When considering the appropriate dosage of creatine for different individuals, I take into account their unique health concerns. For instance, with older adults where dehydration and gastrointestinal issues are prevalent, I would opt for a maintenance dose. I’d start with a low dose and gradually increase it. Although there isn’t substantial evidence on gastrointestinal upset from creatine, I prefer to err on the side of caution, especially when dealing with sensitive patient populations, such as those with muscular dystrophy. It’s unnecessary to disrupt their daily routine with a high intake of 20 grams of powder, divided into multiple shakes, when a single daily dose can achieve the same results with a bit more patience.

Now, regarding the maintenance of creatine levels in the body, it’s important to understand the difference between the creatine phosphocreatine energy system and the carbohydrate energy system. If we don’t consume carbohydrates for 24 hours, our liver glycogen depletes significantly, and our muscle glycogen also decreases. However, if we don’t consume creatine for the same duration, there’s no immediate effect. It can take a few weeks, perhaps three on a vegetarian diet, to see a noticeable decrease in muscle creatine levels.

Once muscle creatine levels are increased by about 20% above baseline, discontinuing creatine supplementation will result in a gradual return to baseline levels over approximately six weeks. To maintain these elevated levels, a daily intake of three to five grams is sufficient. If a dose is missed, there’s no need for panic or to restart the loading cycle, as the decrease in creatine levels will be minimal.

The concept of cycling creatine is also intriguing. Concerns about downregulation, such as the suppression of endogenous synthesis or the downregulation of transporters, are common. However, I often compare this to mineral metabolism. For example, if you’re on a low-calcium diet, your body adapts by increasing absorption from your diet. The same principle applies to iron. Therefore, the body’s ability to adjust is a natural and expected response, and the idea of cycling creatine should be considered within this broader context of how our bodies regulate and adapt to nutrient intake.

In considering the impact of diet on our bodies, it’s important to recognize that an increase in certain nutrients can lead to a corresponding increase in excretion. However, it’s crucial not to become overly concerned, treating nutrients as if they were powerful pharmacological drugs. Our bodies are incredibly adaptive. For instance, if my body decreases its endogenous synthesis of a nutrient because my muscles are retaining more due to supplementation, I see that as a natural adjustment. There’s no need for alarm.

Monitoring urinary creatinine levels has shown that, over time, when individuals stop supplementing, everything tends to return to baseline. It’s a testament to the body’s intelligence and capacity for self-regulation. This is not akin to the effects of anabolic androgenic steroids or testosterone, which can significantly disrupt or even permanently shut down the endocrine system. With a nutrient like creatine, the body’s response is much more benign, so I don’t see a compelling reason to cycle its use.

In fact, if there is some downregulation, I’m inclined to view it positively. It’s simply the body’s way of regulating the concentration within the skeletal muscles. I haven’t come across any data suggesting that cycling is necessary, especially when considering this in the context of other nutrients.

I always encourage a plant-rich diet for both personal health and environmental sustainability. In my experience, there are certain nutrients that those on plant-based diets need to pay extra attention to. These ‘nutrients of focus’ are essential for maintaining energy levels, cognitive function, and overall vitality. To address this, I’ve collaborated with a plant-based health and wellness company to create Essential 8, a comprehensive multi-nutrient supplement. It includes DHA EPA omega-3s from algae oil, vitamin B12, iodine, vitamin D3, iron, zinc, selenium, and calcium—all designed to complement a plant-rich diet.

I take Essential 8 every morning with breakfast, finding it much simpler than taking these eight nutrients separately. The convenience of a monthly subscription ensures I never miss a day, and it’s delivered right to my door. For anyone interested in supporting their plant-rich diet, I recommend checking out Essential 8 for that extra boost to your nutrient intake.

Creatine monohydrate is a topic I’m always eager to discuss, especially when it comes to the various creatine compounds that saturate the health and fitness market. As a researcher actively engaged in the science of these supplements, I find it essential to clarify the differences and the efficacy of these products.

When addressing this subject, I often emphasize a key point in my presentations, which I highlight in all capital letters on my slides, and I make sure to project it loudly to my audience: 99% of the research on safety and efficacy is on creatine monohydrate. There are indeed numerous products that claim to offer increased absorption or other benefits. However, creatine monohydrate is already about 99% absorbed. If there were a way to improve upon that, it would be groundbreaking, but to date, no other supplement has provided muscle uptake data or blood kinetics to support any such claims. Moreover, these alternatives are typically more expensive and contain less creatine than monohydrate.

There is simply no compelling reason to choose a creatine supplement other than creatine monohydrate. Some alternatives have been identified as procreatinine supplements, meaning they don’t increase muscle creatine levels but do increase the level of creatinine in the body. Others contain negligible amounts of creatine. The lack of research in this space is telling; 99% of the safety and efficacy data we have is on monohydrate.

People often ask about the production of creatine monohydrate supplements. It’s important to note that these supplements are synthetic, which means they pose no issues for vegetarians. I’ve visited the company AlzChem Trostberg GmbH, which is one of the last manufacturers of creatine outside of China. They market their product under the Creapure brand, which is the creatine I’ve used in my research, funded by the National Institutes of Health. This is not an endorsement of their product, but rather an acknowledgment of the high standards of purity and quality that I’ve required for my research on humans, which has been approved by the NIH.

AlzChem’s website offers detailed information about the purity and manufacturing standards of their product. For those interested in the provenance and quality of their creatine monohydrate supplement, AlzChem’s Creapure is a brand that provides transparency and assurance regarding the quality of their manufacturing process.

What many people don’t realize is that the supplement industry is not as vast as it seems when it comes to manufacturing. There are numerous supplement retailers, but only a handful of actual manufacturers. When you examine the label on a supplement bottle, you’ll often find phrases like “manufactured for” or “manufactured by,” indicating that the same product, such as Creapure creatine, can be sold under various brand names. Different retailers or manufacturers might offer the same core product with their own branding.

About a year ago, I was invited to join the scientific advisory board of Al’s Chem, a decision that has reinvigorated creatine research and sparked renewed discussions in the field. I’m very pleased with this development. However, I must express my concerns regarding the purity and quality control of creatine sources from other manufacturers. These concerns are not about Al’s Chem’s product but rather about other creatine products on the market. Given the large doses of up to 20 grams per day that are sometimes recommended, the purity of dietary supplements is a significant issue. This isn’t limited to creatine; it extends to herbs, vitamins, minerals, and many other products.

To clarify, Creapure is a proprietary name that indicates a specific source of creatine, which other brands can use to assure quality. Despite the potential appearance of a conflict of interest due to my advisory role, I have no reservations about recommending Creapure. This is because, when faced with the need to prove the safety and purity of a nutrient for human supplementation to an institutional review board or funding agency, I can confidently provide that evidence. This level of assurance is not always possible with some dietary supplement studies.

I believe this information is valuable, and many people will want to use the same creatine that has been used in research studies. It meets a high standard of quality that is not always achievable in the dietary supplement industry.

Now, regarding the synthetic nature of supplements like creatine, this topic often arises in discussions, particularly on social media platforms like Twitter. Some argue that taking a supplement at doses not naturally obtainable from diet alone is “unnatural” and that we should be able to get all our nutrients from food. In response to this, I’ve encountered such arguments numerous times throughout my career. Ultimately, it’s a matter of personal philosophy and how one chooses to interpret nutrition research. If one is comfortable with the idea that all necessary nutrients should come directly from food, that’s a valid perspective. However, supplementation can play a role in achieving specific health or performance goals that might not be attainable through diet alone. It’s a decision that each individual must make based on their own beliefs and the goals they wish to achieve.

The elimination of deficiency diseases, such as rickets, scurvy, and anemia, is certainly a significant achievement in the realm of public health. However, my focus has shifted toward the pursuit of optimal health through nutrition. It’s important to recognize that recommended dietary intakes are not static; they evolve, sometimes quite contentiously. In my teachings, I highlight the dramatic changes in nutritional guidelines by comparing past and current textbook editions. For instance, the recommended dietary intake of vitamin D has tripled, which underscores the fact that nutrition is a very young science.

We’ve made strides in identifying essential compounds and eradicating deficiency diseases, but now we’re at a juncture where we’re considering what constitutes optimal health. This involves questioning the role of various nutrients and supplements, such as vitamin C, calcium, iron, ubiquinol, and antioxidants. The debate often centers on the difference between avoiding deficiency diseases and achieving optimal health.

For example, I’ve been taking creatine long-term, and it raises the question of whether such practices are in conflict with nature’s laws. This isn’t just about individual supplements; it extends to dietary patterns as a whole. Meat consumption, for instance, brings up a host of considerations, including cost, health effects of saturated fat, digestibility issues, and broader ethical and environmental concerns.

In my view, dismissing something solely because it’s “unnatural” overlooks the potential benefits it may offer. It’s crucial to examine the evidence and explore what constitutes adequate nutrition versus what may enhance health span and quality of life. These discussions are part of a larger conversation about combating obesity, physical inactivity, poor fitness, and cardiometabolic disease. Any dietary recommendation that can assist people in improving their quality of life is worth considering, especially given the broader context of food-related health issues.

Business seems to be working against the individual striving to maintain a physically active lifestyle, normal weight, and a nutrient-rich diet. It’s a significant challenge in today’s global environment. This struggle raises big questions, particularly when considering the influx of supplements on the market, many of which lack solid evidence to support their claims. Performance supplements, in particular, tend to attract a great deal of skepticism, more so than something like calcium or vitamin C. This skepticism seems to be part of the territory.

I sense this skepticism personally. It’s present among journal reviewers, grant reviewers, parents, physicians, clinicians, and it’s palpable at conferences. I would argue that there’s an even stronger bias when it comes to products associated with muscle building. The public appears to be more accepting of anti-obesity weight loss drugs, but a nutrient that might build muscle is met with apprehension. Creatine, for example, is a substance that often gets a mixed reception. Some people use creatine to enhance their performance in sports like track cycling or swimming, while others take it to train harder and recover better in the weight room. It improves quality of life by enhancing strength and conditioning.

One could argue that adding creatine to one’s regimen is not very different from increasing dietary protein intake. Creatine may aid in the weight room, while protein is an adaptive nutrient post-training. If you increase the protein content of your diet, is that also going against nature and enhancing performance? Is it unnatural to increase your adaptation to training?

I believe that we must consider the broader implications of these discussions. The same considerations we have for athletes also apply to muscular dystrophy patients, frail older adults, and other vulnerable populations. There’s much more at stake than simply whether or not something is ‘unnatural.’

Furthermore, we haven’t even delved into the potential cognitive benefits that could be available to different populations, which is an area ripe for exploration. To return to the skepticism surrounding performance supplements, some of it may stem from concerns about adverse effects. It’s important to have a balanced view and recognize that while skepticism can be healthy, it should be based on evidence and a comprehensive understanding of the potential benefits and risks involved.

As I delve into the safety profile of creatine, particularly at the levels of a three to five gram daily maintenance dose and the potential 20 to 25 gram daily loading phase for four to five days, it’s important to understand the breadth of research that has been conducted. The majority of studies have focused on young men and women, as well as older adults, primarily those who are healthy. This is a common trend in exercise research due to the exclusion criteria often employed.

In the vast body of literature, there are dozens of safety trials, including randomized controlled trials, that assess the safety of creatine in average individuals, athletes, and even elite athletes. The main areas of concern that have been scrutinized are hydration and thermoregulatory issues, muscle dysfunction, and kidney health.

Addressing these concerns individually, starting with thermoregulatory issues, there is no evidence suggesting any problems related to dehydration or heat regulation. In fact, several studies have shown physiological benefits to exercising in heat when one is creatine-loaded. The military has shown particular interest in this effect. For instance, when individuals are creatine-loaded and placed in a heat chamber, some measurements, such as heart rate, actually show improvement compared to a placebo group. Importantly, there have been no cases where thermoregulatory issues have worsened due to creatine supplementation.

Moving on to muscle concerns, extensive research has been conducted on cramps, strains, muscle tears, and injuries, including lost game time and missed practices. Coaches and athletic trainers often keep meticulous records, allowing for a clear comparison between creatine-supplemented athletes and those who do not supplement. Surprisingly, not only is there no increase in muscle dysfunction, but there is also often improved muscle function, with fewer cramps and strains reported in the creatine group. This has been particularly well-documented in studies where individuals are creatine-loaded and then subjected to intense exercise tests in the lab. Some studies have indicated a protective effect, with less muscle damage, reduced soreness, and faster recovery.

However, it’s important to note that while the research is comprehensive, it is primarily centered on healthy individuals. There is a need for more studies on specific populations, such as women of childbearing age, during pregnancy, nursing, and children, to fully understand the safety profile of creatine for these groups. Nonetheless, the existing evidence strongly supports the safety of creatine supplementation at the recommended doses for the general population.

In examining the safety of creatine supplementation, a thorough review of the literature reveals a consistent absence of evidence for increased damage or dysfunction. There are no findings to suggest that creatine intake disrupts thermal regulation, muscle function, or kidney health. This topic has been rigorously investigated, with some studies spanning several years, yet the results remain reassuringly negative for adverse effects.

Occasionally, a small increase in creatinine levels is observed, which I personally consider to be inconsequential. This is particularly true for large athletes who consume creatine; their bodies naturally produce more creatine, leading to a higher urinary creatinine output. Even when blood creatine levels show a slight rise, as long as they remain within the normal range, there is no cause for concern. Such an increase might simply indicate the limitations of the test rather than a health issue. In fact, serial measurements of blood creatine could be useful for monitoring renal function over time. For someone my age, a consistent upward trend in creatinine levels would warrant further investigation. However, for a muscular athlete with increased creatine turnover, these minor fluctuations are likely insignificant.

Renowned labs, including a team in Brazil, have employed sophisticated methods to assess renal function in the context of creatine supplementation. Their findings are clear: no detrimental effects have been identified. This holds true across various aspects of health, including thermoregulation, muscle function, and kidney health. Furthermore, safety trials conducted on vulnerable populations, such as ALS patients, have also concluded that creatine is a very safe and well-studied supplement. It should come as no surprise, given that creatine is a nutrient, not a drug.

The South American lab in question is led by Hamilton Rochelle, a respected figure in the field of kidney research. He has appeared on our show and is a friend of the podcast. His team’s work is exemplary, and I have had the pleasure of collaborating with them on several occasions. Rochelle is not only a great scientist but also a wonderful person. I cherish the idea of visiting them again and perhaps conducting some engaging creatine studies in São Paulo.

While discussing the safety of creatine, I’d like to address a specific concern that has been raised: the potential for creatine to increase hair loss in men who are genetically predisposed. This concern seems to stem from the belief that creatine elevates DHT levels, which could theoretically affect hair follicles. However, upon reviewing the available evidence, it appears that there is little to support this claim. The origin of this concern may be traceable to an older study, but as of now, the connection between creatine and hair loss remains tenuous at best.

There was one study that showed a small increase in dihydrotestosterone, or DHT levels, which are associated with male pattern baldness. Medications designed to slow down baldness typically act as DHT blockers or inhibitors. On paper, it makes sense, but I’m not quite sure that one study, which indicated an increase in DHT levels over 20 years ago and has never been reproduced, is enough to set off the alarm. After all, we’re talking about a nutrient here. If I were to eat two large steaks a day, would you expect me to have accelerated hair loss? When you put it in the context of food, the idea starts to sound strange.

I’m aware there’s a clinical trial currently underway to really address this issue, but it’s ongoing, so we don’t have the results yet. It’s fascinating how one study, one odd finding, could gain so much attention. I wouldn’t expect creatine to have a major impact on the endocrine system because it’s involved in energy metabolism; it doesn’t typically cross over into endocrine functions. It’s a fundamental scientific principle to look for reproducibility in findings, so it will be interesting to see what the new study reveals.

Regarding weight gain, I know that some athletes, like boxers or bodybuilders, who are conscious of their weight, especially leading up to events, often avoid creatine for fear of water retention. Creatine does increase total body water, just as carbohydrate loading does. There’s this fear of water retention with creatine, yet it’s accepted when it’s due to glycogen, which retains three times its weight in water. Marathon runners and cyclists manage this, but the thing about creatine is that once your muscles are loaded with it and it attracts water, you can’t simply remove it from the muscle cells by not consuming creatine for a day.

Anyone who has experimented with low-carbohydrate diets and weight loss knows that reducing carbohydrate intake can lead to rapid weight loss in a few days, with most of that being glycogen and water. However, if you’ve elevated your creatine stores, you’re going to have an elevated body weight for the next four to six weeks, even if you stop taking creatine. So, if you’re struggling to make weight, please stay away from creatine. I don’t want it to drive you to even more unhealthy weight restriction or weight loss practices.

In the realm of competitive sports, particularly those with weight class restrictions, the use of creatine as a supplement requires careful consideration. A case study we published highlighted an individual who, even after a month off creatine, had muscle creatine levels that remained over 20% elevated, and his body weight was significantly increased after 30 days without the supplement. This is particularly relevant for athletes who are high responders to creatine and need to maintain a certain weight class. It’s crucial to understand that correcting the increased body weight and creatine levels in the muscles may take a full four to six weeks.

This brings us to an important message for athletes: the decision to use creatine must be informed by the potential impact on weight and the time it may take to reverse these effects. While weight class considerations seem to be more of a common-sense issue, the scientific community has yet to fully explore the nuances of creatine-induced weight gain. Not all of the weight gain is metabolically active tissue; some of it is simply water retention. In endurance sports, a slight decrease in body weight can lead to increased efficiency and speed over long distances. Conversely, a gain of one or two percent in body weight could potentially slow an athlete down.

However, in sports that involve short bursts of energy, such as sprints, the metabolic benefits of creatine, which include enhanced ATP production, seem to outweigh any potential disadvantages of weight gain. This is also true for sports where the athlete is seated, like rowing, where the metabolic advantage of higher starting muscle phosphorus levels can lead to sustained power and endurance without the weight gain being a significant factor.

But what about swimming? Does the increased body mass from creatine supplementation lead to greater resistance in the water? While there is evidence of creatine’s ergogenic effects in swimming, the weight gain issue is more pertinent in weight-bearing sports like running, especially over long distances. Most long-distance runners likely do not use creatine, as the potential benefits may not be as pronounced.

In team sports such as soccer, the metabolic benefits of creatine can provide a competitive edge, potentially offering an athlete an extra half step or more over an opponent. Here, the metabolic benefits can indeed outweigh the weight gain. In summary, the decision to use creatine should be based on a thorough understanding of its effects on body weight and performance, particularly in relation to the specific demands of the sport in question.

In most situations, it’s conceivable that there could be a sport where weight gain might present a biomechanical disadvantage. This wouldn’t necessarily mean avoiding creatine altogether, but it might require careful timing of supplementation, ensuring there’s enough time to reduce body weight before an event. Creatine could be used in the off-season as part of a strength and conditioning program, depending on the athlete’s needs.

While I haven’t come across any evidence suggesting an ergolytic effect, or a performance decrement due to creatine, the theoretical biomechanical disadvantage of being heavier cannot be ignored. Research has shown that strapping weights to individuals and having them run long distances does slow them down. However, we’re talking about a small amount of evenly distributed water weight, which comes with a metabolic improvement.

The prevalence of creatine use among athletes, whether amateur or elite, varies significantly. My interactions with the International Olympic Committee and renowned international scientists have highlighted that supplement use differs greatly from country to country. What’s emphasized in the United States may not be the same as in Finland, for example.

Furthermore, the level of creatine supplementation is highly sport-specific. In American gridiron football, for instance, you might find very high levels of creatine use, even at the high school level. In gymnastics, it’s less common among women but possibly more prevalent among men. Track and field athletes also make use of creatine. The rates of creatine use I’ve seen range widely, with bodybuilders, powerlifters, and dedicated gym-goers at the highest end, with usage between 85 to 100 percent. For other athletes, studies have reported usage as low as 10 percent and as high as 55 percent, but it’s so dependent on the sport and sometimes even the position within the sport.

The issue of gender representation in scientific studies is also pertinent. Women are often underrepresented for a variety of reasons, including the complexities of including them during pregnancy and different life stages. When it comes to creatine research, the extent to which women have been included is an important consideration. The same benefits and effects observed in men may not necessarily apply to women, and this needs to be addressed with more inclusive research.

When considering the benefits available for women, as one might expect for men, it’s important to delve into the safety profile for specific populations, such as pregnant and nursing women. From a general population perspective, the majority of data are in males, which is unfortunate. However, there have been studies focusing on women, and the ergogenic effect of creatine appears to be similar, meaning that creatine is effective, particularly in the weight room. The weight room activities are well-suited for the phosphocreatine energy system.

Although there are fewer efficacy and safety studies for women, the evidence suggests that if there is any difference between men and women in response to creatine supplementation, it is incredibly small or possibly obscured by individual differences. For instance, women may not be vegetarians but might consume low amounts of meat, or a small study might include individuals with naturally high creatine levels. Whenever literature suggests a potential difference, I remain skeptical. I believe the response to creatine supplementation is the same for men and women.

Emerging research, which is still quite limited, is examining creatine use across pregnancy, employing various laboratory and animal models. So far, everything looks very safe and promising. Experts like Abby Smith-Ryan, who has significant expertise in this area, would likely concur. It’s curious why we start with the presumption of an adverse event when discussing a nutrient. If this were a study on carbohydrate or vitamin C supplementation, would we be questioning a difference in metabolism in women?

Of course, caution is always warranted in pregnancy studies. But consider this: if a pregnant woman consumes a hamburger with a high amount of creatine, are we concerned? Generally, the answer is no. This raises an interesting point about how our hypotheses may be shaped by bias. For example, when we look at omega-3 DHA intake, it is lower than what many suggest is optimal during pregnancy. The hypothesis is that adding DHA during pregnancy will be beneficial. This illustrates how our starting point in research can differ, and it’s essential to examine these biases critically.

Certainly, there is a point to be made about the ergogenic bias and the muscle-building bias that has historically influenced research. I’m pleased to report that the number of studies involving women has increased, and there are many dedicated researchers working in this field now.

When it comes to young children and the appropriate age for creatine supplementation, the answer is nuanced and context-specific. I approach any supplementation use in children and adolescents from a behavioral perspective before considering the physiological aspects. The starting point should always be to address training, diet, and sleep. If these foundations are not in place and one is attempting to compensate for poor habits with dietary supplements, that’s an inappropriate approach.

There are indeed a few well-conducted studies on creatine supplementation in adolescents. The ergogenic effects observed are similar to those in adults, depending on the individual’s starting level of muscle creatine and the magnitude of the increase achieved. However, I emphasize the importance of emotional or maturational age, rather than chronological age, when considering supplementation. I strongly advocate for proper training, adequate sleep, and sound nutrition before introducing supplements. Observing young people in the gym, it’s clear that supplements cannot correct inadequate training regimens.

It’s a good reminder for everyone not to overlook the fundamental aspects of health and fitness, which are the true building blocks for progress. As for the question of dosage, science has validated certain maintenance and loading doses. Exceeding these dosages is not typically recommended, and there is indeed an upper limit established for safety reasons. For the general population and even healthy older adults, adhering to these guidelines is the best practice to ensure safety and efficacy.

I believe that 20 grams per day of creatine is adequate for most individuals. When examining urine data during a five-day loading phase, by day three, there’s evidence of 10 grams of creatine being excreted, indicating that about 50% is not retained by the body. It’s clear that we don’t need excessive amounts like 30 or 40 grams per day. A regimen of 20 grams per day for five days suffices for 99% of the population. However, there are exceptions, such as patients with Huntington’s disease, who may require higher doses, like 40 grams per day.

When considering different tissues, such as the brain, the required dose could vary. The brain is a highly metabolic organ that needs to produce adenosine triphosphate (ATP). It relies on creatine and phosphocreatine to replenish ATP during periods of high activity. Unlike skeletal muscle, which does not synthesize creatine and must obtain it from external sources, the brain manufactures its own creatine and regulates its content. The brain is also very protective, with a blood-brain barrier that is resistant to most substances, including supplemental creatine.

Under normal circumstances, the brain manages its creatine levels effectively. However, in extreme cases, such as children with genetic defects affecting creatine synthesis or transport, supplementation can significantly increase brain creatine levels and restore health. The more challenging question is whether someone without such conditions can enhance their brain creatine levels through supplementation and, if so, what cognitive benefits might result. There is a small but intriguing body of literature exploring whether brain creatine levels can be increased with supplementation and the potential cognitive enhancements that might follow.

The answer appears to be yes. There are, I believe, a dozen creatine supplementation studies that have been conducted with pre and post brain measurements. Nine out of the twelve have shown a significant increase in brain creatine. However, this increase is more on the order of five percent.

Now, when it comes to measuring creatine in the brain, it’s undoubtedly more challenging than in skeletal muscle. With muscle, we operate under the assumption that a biopsy of the vastus lateralis reflects what’s going on in the entire muscle. We can compare creatine content across labs from different countries and it makes sense, thanks to the muscle biopsy technique.

However, when using magnetic resonance spectroscopy, we can’t compare actual concentrations across labs in the same way. We can compare percent change, but not the actual concentration. With a muscle biopsy, I can look at a study from Australia and confidently interpret the creatine levels. But with brain measurements, I have more confidence in stating a percent change post-supplementation than in comparing the actual concentrations.

We obviously cannot perform biopsies on the brain, so we have to use spectroscopy. You lie in an MRI machine, and it’s through this process that we measure the creatine content. There are indeed differences in creatine content across different regions of the brain, which adds another layer of complexity. We have yet to standardize which part of the brain we should all be examining.

The very first study on this topic, conducted by Descent and colleagues in 1998, demonstrated that oral supplementation could increase brain creatine by about 10 percent, which is less than the increase in muscle. They also showed that pre to post measurements in different regions of the brain could yield vastly different results. This highlights the importance of either measuring several regions or ensuring consistency across studies in the regions being measured.

In conclusion, to investigate creatine supplementation effects on the brain, one must have access to an MRI capable of spectroscopy and a vested interest in the topic of creatine supplementation.

Research on the brain is significantly less extensive than that on muscle. It’s been observed that young individuals with traumatic brain injury might benefit from supplemental creatine, which could potentially cross the blood-brain barrier. This seems to be a natural response of the body, allowing creatine from the peripheral system to enter the brain when endogenous production is insufficient. The brain may reduce its own creatine production, or the need for creatine may increase, especially during a traumatic brain injury, which triggers an energy crisis. Studies have shown that brain creatine levels drop following a concussion, suggesting that supplementation could be advantageous in such situations.

During this energy crisis, the brain experiences depolarization of membranes and requires additional energy, which is when acute supplementation of creatine could be particularly beneficial. This is not only true for acute conditions like brain injuries but also for chronic energy deficiencies seen in conditions such as schizophrenia, certain types of depression, and even physical frailty in old age. These scenarios indicate a long-term, chronic reduction in brain creatine that could also be improved with supplementation.

Regarding clinical trials, the research on depression is quite robust. Teams specializing in clinical psychology and spectroscopy have explored the effects of creatine supplementation on depression, particularly drug-resistant depression in women. They’ve observed increases in brain creatine and some alleviation of depressive symptoms, which points to a well-defined and strong body of literature. However, the literature on concussions is primarily based on theoretical models, animal studies, and some observational research.

I refuse to delve into the topic of animal research, but when it comes to creatine, there’s an abundance of research confirming its efficacy and safety. It’s also relatively inexpensive and widely available. For individuals at high risk of brain injury, perhaps due to participation in high-risk sports, it seems prudent to recommend the addition of creatine supplements to their diet. While I’m not a proponent of relying on animal data, the evidence is compelling. Studies have shown that hypoxic or traumatic brain injury in animals can result in a significant reduction in tissue damage—up to 50%—when the animals are preloaded with creatine.

Furthermore, there’s intriguing research from a lab in New Zealand where a hypoxic challenge was simulated by having people breathe low oxygen air, which induced concussion-like cognitive deficits. These deficits were mitigated when individuals were supplemented with creatine. The damage was attenuated.

Some of the most persuasive data come from open-source trials in hospitals involving children with brain injuries. Several studies have demonstrated remarkable improvements in recovery from brain injury in these young patients. The benefits seem to be comprehensive, improving mood, reducing fatigue and headaches, and enhancing mental clarity. These findings have been particularly evident in hospitalized children.

There’s ongoing research with collegiate athletes, although this is challenging due to the unpredictability of concussions and their severity. However, it’s worth noting that there has been a study focusing on retired NFL players who have suffered repeated head injuries and continue to exhibit related symptoms. These individuals have shown depressed levels of brain creatine, suggesting a long-term energy deficit in the brain.

Given the well-documented safety and effectiveness of this inexpensive supplement, it’s perplexing why there’s any hesitation in its use, especially in instances of brain injury. It would be fascinating to see if creatine supplementation could bring cognitive improvements in retired athletes if studied in a randomized controlled trial.

The cognitive studies are interesting in their own right. It appears that those who can measure cognitive improvements pre and post-supplementation aren’t the same researchers who can measure brain creatine levels. This disconnect points to the need for more integrated research approaches to fully understand the potential benefits of creatine supplementation on brain health.

In the realm of brain health and cognitive enhancement, the studies measuring brain creatine levels are quite limited, with Hamilton’s group being one of the few to explore this area. They’ve investigated the effects of creatine supplementation on both brain creatine levels and cognitive performance. To date, there are 16 cognition studies, and an impressive 13 of these have demonstrated improved cognitive performance following supplementation. The research has covered a diverse group, including vegetarians, older adults, and individuals both well-rested and those under stress from sleep deprivation or strenuous exercise. The findings are compelling, showing that creatine can help mitigate the cognitive disruptions caused by such stressors.

The consistency of these findings across different studies is what fuels my optimism. We’re seeing improvements in various aspects of cognition, which is quite remarkable for a single nutrient. This leads to the question of whether creatine’s cognitive benefits are solely due to its role in brain energy metabolism or if there might be other pathways at play. For instance, could creatine influence glucose metabolism or other bodily functions? While it’s always a possibility, the current body of research doesn’t strongly support these alternative mechanisms. The most plausible explanation seems to be that creatine supplementation is particularly beneficial in situations where the brain is facing an energy crisis, whether it’s due to chronic conditions, acute injuries, or the natural effects of aging.

The potential for the average person to increase their brain creatine stores by five to ten percent is intriguing. When considering the appropriate dosage to achieve this, we’re somewhat in the dark, as the specific dose-response relationship for brain creatine has not been thoroughly investigated. Consequently, the recommendation is to follow the dosing protocols established for muscle studies, which are well-documented in terms of safety and efficacy. Although we have some evidence suggesting that these doses can effectively increase brain creatine, we’re still in need of more targeted research. Unfortunately, practical limitations often hinder such studies, as access to the necessary equipment, like MRI machines, is limited and frequently prioritized for diagnostic radiology over research purposes.

In my work, I’ve come to realize that my little creation studies simply don’t hold up against real clinical diagnoses. When you have access to a research-dedicated magnet, you can pursue this kind of research, but such resources are scarce. We can’t perform brain biopsies, so the literature on this topic is growing slowly. I’m hopeful that I’ll be able to conduct some escalating dose studies, even on a case study basis. This would allow us to give the same individual multiple MRIs to track brain creatine levels, similar to what we’ve done with muscle and urine at different doses to observe the skeletal muscle response. These types of investigations are on the horizon, but progress will be slow due to the impossibility of brain biopsies, at least at my institution.

When considering individuals who play contact sports, such as NFL players, the question arises whether it’s a good idea to supplement with creatine, not just for performance benefits but also for potential protective benefits in the brain. I believe that this discussion is happening within the NFL and the NCAA, likely at the team level, among sport nutritionists and sports scientists, though it may not be a widely publicized conversation.

In our latest review on creatine and brain health, we conclude with the question of whether it’s more prudent to ingest a nutrient that not only improves muscle function and has ergogenic benefits but also boasts an excellent safety profile. Given that many diets might be deficient in creatine, it’s inexpensive, widely available, and could potentially reduce the severity of or enhance recovery from traumatic brain injury in contact sports, it seems wise to recommend supplementation. Especially for high-risk players or those who have already suffered concussions, it may be more prudent to proceed with supplementation rather than wait for additional research.

Regarding vegetarians and cognition, a study by Benton and colleagues, conducted around 2010 or 2011, comes to mind. They looked at the effects of creatine supplementation over a short period, around four or five days, and its impact on cognitive function. This research is particularly intriguing and adds another layer to our understanding of creatine’s potential benefits beyond muscle and athletic performance.

In examining the impact of creatine supplementation on cognitive function, there was a particular study that caught my attention due to its intriguing findings. The research in question involved a daily intake of approximately 20 to 25 grams of creatine, and it revealed a significant difference in memory performance between vegetarians and omnivores. This study has been interpreted in various ways, depending on one’s dietary perspective, which is always interesting to observe. Different lenses offer different interpretations, and it’s fascinating to see how people arrive at their conclusions.

Upon closer inspection of the study, the baseline data indicated that both groups performed similarly at the outset. However, after the period of supplementation, the vegetarians exhibited a greater improvement in cognitive function. This raises questions about whether this is a negative finding for vegetarians or if it actually highlights a positive aspect of creatine supplementation for cognitive benefits in those who follow a plant-based diet.

As a muscle physiologist, my focus has traditionally been on everything below the neck. It wasn’t until my research on creatine led me into the realm of brain health that I began to consider cognitive functions. This prompted me to reach out to experts in psychology, including military psychologists adept at measuring brain performance. What I quickly discovered was a disconcerting lack of consensus among labs regarding cognitive assessments. While strength and muscle power can be measured consistently across the globe, cognitive functions such as memory and mathematical processing are evaluated using a variety of methods, leading to disagreement and skepticism among researchers.

This discrepancy was particularly frustrating as a young investigator. I would present papers from reputable labs and journals to psychologists, only to be met with disbelief and rejection of the methodologies used. This made it challenging to compare studies and draw definitive conclusions.

Nevertheless, one of the most significant contributions to this field of research came from a team in Brazil, led by Solis as the first author. Their work provided valuable insights into the differences in cognitive performance between vegetarians and omnivores, further emphasizing the complexity and importance of this area of study.

Omnivores typically have higher muscle creatine levels to begin with, and when vegetarians are supplemented with creatine, they tend to show a larger increase due to starting from a lower baseline. If we examine the diets, vegetarians consume almost no creatine, while omnivores consume a significant amount. However, when we look at brain creatine levels, they appear to be identical between the two groups. It seems as though the brain has its own mechanism for managing creatine levels, particularly in response to a vegetarian diet.

Upon supplementation, the response in the brain may not mirror that of muscle tissue. In some instances, we might not see any increase in brain creatine levels in either vegetarians or omnivores. This suggests that the brain should be considered differently from skeletal muscle. It’s fascinating that out of 16 studies on creatine and cognition, 13 have shown a positive effect on cognitive function. Yet, there’s no consistency in the methodologies used across these studies; they all employed different tests and examined diverse populations.

In particular, when considering the elderly, it’s unclear whether their dietary creatine intake is more aligned with that of vegetarians or omnivores. The literature in this field is complex and somewhat disorganized, but the consistent finding of improved cognition is incredibly motivating. It inspires me to continue my research in this area. While I expect vegetarians to have a more pronounced response in muscle creatine levels, I’m less certain about the brain. I believe the brain maintains its creatine levels quite robustly. Becoming a vegetarian might not deplete brain creatine as significantly as it does creatine in the blood and muscles.

As for the future of research in this space, there’s a pressing need for a group that can accurately measure both cognition and changes in brain creatine levels. This will likely require a collaborative, multi-site effort. Currently, we have separate sets of data on brain creatine and cognitive function with almost no overlap. The first step might be to conduct studies that can bridge this gap, even if it means repeating some of the previous work to ensure more reliable and comprehensive results.

In exploring the potential benefits of creatine on cognitive processing, it’s essential to begin with brain measurements in young, healthy individuals, including both vegetarians and omnivores. Understanding the correlation between brain creatine levels and cognitive outcomes is the first step. Once established, we can extend the research to different populations, such as older adults or comparing vegetarians with non-vegetarians.

Conducting small dose escalation studies or case studies would be extremely valuable. With individual participants, we can perform multiple MRI scans and measure creatine levels in various parts of the brain, something that’s challenging to do in large randomized controlled trials. The key is to determine if there’s a link between brain creatine and cognition, addressing the question of whether the benefits extend beyond simply improving brain energetics.

Another intriguing aspect is the delivery method of creatine, considering the blood-brain barrier. It’s possible that a different creatine compound could be more effective in penetrating brain tissue. While there are more efforts in the industry to create marketable products, there’s a need for academic research to answer these questions. Serge Osick has conducted research on guanidinoacetate, a precursor to creatine, which is promising. Historically, feeding people precursors rarely results in the formation of the desired product, but in this case, it appears to increase brain creatine and improve cognition.

Despite the industry’s tendency to rush products to market based on preliminary studies, such as those involving rats, a cautious approach is warranted. Precursor compounds do seem to have potential, but we must consider the brain’s protective mechanisms. For instance, the brain is resistant to insulin, which facilitates glucose and creatine uptake in muscles. Therefore, simply adding carbohydrates and proteins may not be effective.

However, creatine monohydrate, given in the right dose at the right time to the right population, holds promise. It’s an area that continues to be fascinating and warrants close attention. The potential for creatine to enhance cognitive function is certainly an exciting prospect in the field of dietary supplements and brain health.

Informative indeed, I’ve learned a lot and I’m grateful for the opportunity to share this knowledge with everyone. There’s always more to discuss, especially when it comes to creatine. I could talk about it for weeks on end. However, to spare everyone from a lengthy discourse, I’ll share something valuable. Recently, there was a creatine conference that brought together some of the world’s leading creatine researchers. They published a collection of articles and made them all open access.

The journal Nutrients has an entire issue dedicated to creatine, which is a fantastic resource for anyone looking to delve deeper into the subject. It’s a treasure trove for those who want to explore their specific interests in detail.


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