Introduction
Creatine is one of these not the most highly studied molecules on the face of the Earth. The reason creatine has been studied so vehemently is because researchers know that creatine is safe, effective, and its positive attributes are multifactorial. If you're looking for a safe and inexpensive way to increase energy, cognition, physical performance, fertility, the function of every major organ system and body composition… creatine is for you.
What is creatine
Creatine is classified as an amino acid that is created inside the body. The creation of creatine begins with two amino acids, arginine, and glycine, mainly within the kidney. The kidneys release a compound called guanidinoacetate (GAA), which is then converted into creatine in the liver using a third amino acid called methionine, predominantly in the liver. However, creatine synthesis also occurs in the kidney, pancreas, and importantly inside of the brain. In fact, it's thought that the majority of creatine present inside of the brain was created inside the brain, and was not derived from the available creatine within the blood (3). It's estimated we naturally produce approximately 1-2 grams of creatine every day, which could potentially be mildly increased by a higher protein diet, which would provide more of the substrate required for creatine synthesis (7).
Creatine storage
Creatine is stored within many different tissues within the body including the kidney, brain, liver, and even inside the eyes and ears. Approximately 95% of the creatine in the body is found inside skeletal muscle (4). It is estimated an individual can store as much as 160 g of creatine inside the body, and this is highly dependent on body size and muscle mass (5).
Natural degradation
It is estimated that we lose approximately 1-2% of our creatine stores every day. Thus, the more creatine stores you have, the more creatine you will lose daily. Creatine loss occurs due to the Degradation of creatine into an unusable compound called creatinine in what is referred to as a dehydration reaction. Dehydration is the term given to a chemical change that removes water from a molecule to form a new compound. In this case, dehydrated creatine is called creatinine. The dehydration of creatine is thought to occur randomly and occurs at the rate of approximately 2 to 3% of our whole body creatine stores per day. However, the dehydration of creatine increases during exercise. Moreover, the more intense the exercise is, the more creatinine will be formed. This effect occurs due to a decrease in cellular pH levels that occurs during exercise, which increases the rate of creatine degradation. The degradation of creatine into creatinine is increased in an acidic environment. As muscular pH decreases, you will begin to feel a greater degree of pain and sensations of “burning” in the muscle. Thus, pain perception during a workout is a proxy for a decrease in cellular pH, thus an increase in creatine degradation (6).
Dietary creatine
Creatinine can be derived from foods in fairly high quantities. Creatine is only found in animal products because plants do not naturally produce creatine, but animals synthesize and store creatine just like humans. With that being said, you would have to eat a fairly large amount of certain animal foods every single day to obtain the same amount of creatine you would get through a supplement. Relying on food to get all of your creatine could be a feasible way to maintain adequate creatine stores once creatine stores are fully saturated. It might be difficult to reach full saturation by relying only on food, and it would take more time to build up creatine stores through the amount of creatine you will derive from food, but it certainly could be achieved.
Creatine supplementation
Creatine loading
As mentioned, it's estimated humans can store up to about 160 g of creatine. Given that creatine loss is about 2 to 3 grams per day, and we synthesize approximately 1-2 grams per day, the ingestion of approximately 2 g per day is likely sufficient to maintain our current creatine stores of a 150-pound individual. Your dose should scale dependent on body weight, physical activity, and muscle mass. To increase creatine stores to maximum levels, a 150-pound person would aim to exceed the daily dose required to maintain creatine stores (2 grams per day) by approximately 160 grams, taken over at least 14 days. Once this has been achieved, for a 150-pound individual oral dosing of approximately 2 grams per day can maintain muscle creatine levels at maximum concentration. However, going beyond this intake may positively impact other organ systems, namely the brain, as I will discuss in a moment.
Effects of creatine
ATP production
Now that you know all about creatine storage, let's talk about why you'd want to have creatine stores in the first place! Inside the cells, creatine interacts with an enzyme called creatine kinase, which adds a phosphate group to creatine, creating creatine phosphate (PCr). PCr is extremely important, as you will find out in a moment.
To frame this discussion, it's important that you understand the role of ATP in human biology. Almost every single physiological process uses adenosine triphosphate (ATP) as a source of energy. The body breaks down macromolecules (glucose, fatty acids, amino acids, lactate, etc...) to power the phosphorylation (meaning to add a phosphate) of ADP, creating ATP.
In essence, all of the food that we eat is used to add a single phosphate group onto ADP in order to create ATP. There is energy stored inside of the bond between the second and third phosphate. This energy is used to power just about every single function in the body, including breathing, movement, thinking, the heartbeat, etc….When ATP is utilized outside of the mitochondria in a location referred to as the cytoplasm. When ATP is used for energy it is converted back into ADP.
PCr is present in the cytoplasm, in extremely close proximity to the site of ATP usage. When ATP is converted into ADP, PCr can quickly dominate its phosphate to ADP, regenerating ATP.
The reason we are unable to continue exercising forever is that we do not have enough run ATP within the cell because we are unable to make it quickly enough. PCr can quickly regenerate ATP during exercise, and even during everyday life, in order to maintain a supply of ATP for a longer period of time. The energetic benefits of creatine are not extreme in magnitude, however, it has been shown in multiple publications that the performance increases derived from creatine are not negligible (8).
Creatine's role on ATP resynthesis is the main reason why creatine positively impacts virtually every organ system, workout performance, cognitive performance, and most other facets of health. Due to creatine's role in ATP resynthesis, via this mechanism creatine will make you feel and perform better than you did before.
Water distribution
When talking about creating, I think it's important to address the issue of "water weight". Creatine will increase the amount of water stored inside of your body. The reason for this is that the body will always fight to maintain what is referred to as osmolality. This is the ratio of solutes to liquid within three main tissue compartments: inside the cell, inside the blood, and surrounding the cell.
Creatine is a solute, therefore wherever creatine is stored, we will also store a certain amount of water to maintain the proper ratio of solute to liquid. With that being said, creatine is stored inside the muscles. Thus, creatine will increase the amount of water stored inside of the muscles, not the amount of water stored inside of the bloodstream or the interstitial space. The potentially dangerous and unsightly accumulation of water occurs when water is retained within the bloodstream, raising our blood pressure, and within the interstitial space, referred to as edema. However, creatine will increase water content within the muscle, which has the effect of increasing muscular size, which consequently makes the muscles larger and more defined. Moreover, this intracellular water can aid in preventing a certain degree of muscular damage and has other beneficial attributes (9).
Recovery and muscle damage
Creating supplementation improves subjective and objective recovery, and decreases muscle breakdown during and after exercise. This is likely due to its ability to enhance protein synthesis and decrease protein breakdown. Additionally, due to creatine's capacity to reduce the accumulation of metabolic waste products, creatine aids in returning the muscle cells back to homeostasis by removing waste products more efficiently. Moreover, creatine increases ATP availability for the energy-intensive recovery process, and increases cellular hydration (11).
Creatine in the brain
The brain is one organ that also uses a very high amount of creatine. With that being said, the brain is fairly resistant to the uptake of creatine from the bloodstream, as the brain produces the majority of its creatine. Due to the low uptake of creatine from the bloodstream, higher doses of creatine may be warranted to increase brain levels of creatine. However, creatine supplementation does appear to be able to improve the concentration of creatine inside of the brain. Importantly, it does appear that brain creatine is diminished during sleep loss and head trauma. Thus, creatine supplementation has been efficaciously used in these situations to improve cognitive function, memory, and cognitive outcomes. Moreover, supplementation of creatine appears to improve memory, specifically in vegans and vegetarians who do not consume enough creatine daily (19).
In essence, it does appear that high-dose creatine is wanted to improve cognitive outcomes. Within the brain, creatine has numerous roles related to energy production and maintenance, which aids in memory, cognition, and recovery from cognitive insults such as sleep loss or head trauma. Creatine also appears to be an application supplement to fight off cognitive decline and improve cognition in patients with neurodegenerative pathologies (12).
Creatine and the heart
Creating plays a vital role in maintaining energy availability in the heart, and reducing the likelihood of heart dysfunction (13 ). Creatine acts to increase the ATP supply to the heart, which is pivotal for maintaining the balance of electrolytes within the heart. Electrolytes, such as sodium and potassium, are vital for maintaining proper heart rhythm, contractility, and efficiency. Energy is required to set up a concentration gradient of sodium and potassium is in the heart, of which creatine is able to supply.
Creatine and the immune system
Creatine has shown a substantial degree of efficacy in improving the immune system, which is one mechanism by which creatine enhances recovery from exercise. Because the immune system is such an energy-intensive system, the increased production and availability of ATP supported by creatine can enhance the immune response and immune defense, such as defense against pathogens, bacteria, and viruses (14).
Creatine and fertility
Interestingly, it does appear that similar to the way that creatine provides energy to the brain and muscular system, creatine is used as an energy source for sperm, allowing them to swim up the vaginal canal in order to fertilize an egg. Thus, creatine supplementation in both men and women trying to reproduce may be an efficacious fertility protocol to increase the likelihood of impregnation (18).
Creatines role in longevity
Hopefully, it is evident that creatine can improve lifespan and quality of life concomitantly. As aforementioned, creatine plays a role in both muscle strength and muscle size, both of which are extremely important factors when it comes to the risk of physical injury and deterioration later in life. Furthermore, diabetes and other metabolic disorders can reduce both one’s health span and lifespan as well. The growth and maintenance of muscle mass is a key factor in regulating our risk of diabetes and metabolic diseases, with low muscle mass being a positive predictor of the onset of diabetes and metabolic disorders (17). Creatine's critical role in muscle health, function, and growth makes creatine an important molecule for preventing the onset of these metabolic disorders, helping to increase both health span and lifespan.
Moreover, creatine has demonstrated in a multitude of ways that it can help prevent, and remediate cognitive decline as we age, including playing a role in preventing the onset and symptoms of age-related diseases such as Parkinson's and Alzheimer's disease (15). Thus, creatine can improve lifespan by preventing possibly fatal mental and physical deterioration, and also improve the quality of life by improving mental and physical capabilities.
In addition, as mentioned, creatine plays a vital role in the immune system. The immune system is extremely important for ensuring we do not fall victim to widespread infections that could possibly be life-threatening. Lastly, I mentioned that creatine can also help support the heart and many other organ systems, all of which decline in function as we age. It is evident by way of creatine’s numerous mechanisms that it could potentially be a healthspan and lifespan-promoting molecule, and the research does appear to back up this hypothesis (16).
Conclusion
There are many myths and misconceptions about creatine, which have been reviewed multiple times in different publications. That being said, creatine, is one of the most, if not the most, rigorously studied and tested compounds for exercise performance and overall health. Any case reports of detrimental effects of creatine are scarce, and typically only occur in individuals with underlying pathologies, such as kidney abnormalities. Moreover, creatine is a naturally occurring compound found in our food, but the addition of creatine supplementation can further increase the beneficial effects of creatine by saturating creatine stores. Importantly, many studies indicate that individuals with diets low in creatine, such as vegan or vegetarian diets, respond even more favorably to creatine than an individual on an omnivorous, meat-heavy diet. The roles of creatine in the human body are akin to the roles of glucose, fats, and proteins, and numerous more roles of creatine are continuing to be discovered. Creatine is inexpensive and efficacious and should be considered as one of the fundamental supplements for almost anyone's lifespan-extending protocol.
ABOUT THE AUTHOR
Calvin, an industrious individual with a profound interest in human physiology and nutrition, has been ardently pursuing his passion since the age of 13. Earning the distinction of valedictorian at his high school, Calvin is currently enrolled in college, where he is diligently working towards obtaining a degree in biology with a specialization in bio-process technology. Remarkably self-taught, Calvin’s pursuit of knowledge has surpassed conventional
expectations. His dedication to studying is exemplary, outclassing the efforts of many in his field. Calvin possesses a wealth of expertise in biohacking, a subject he has delved into for several years. Through his endeavors, he has acquired a comprehensive set of tools aimed at optimizing health, energy levels, and longevity.
@calvin_scheller
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