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The team includes nutrition researchers, registered dietitians, physicians, and pharmacists. We have a strict editorial process. This page features references.
All factual claims are followed by specifically-applicable references. Click here to see the full set of references for this page. Creatine is a molecule produced in the body.
It stores high-energy phosphate groups in the form of phosphocreatine. Phosphocreatine releases energy to aid cellular function during stress. This effect causes strength increases after creatine supplementation, and can also benefit the brain, bones, muscles, and liver.
Most of the benefits of creatine are a result of this mechanism. Creatine can be found in some foods, mostly meat, eggs, and fish. Creatine supplementation confers a variety of health benefits and has neuroprotective and cardioprotective properties. It is often used by athletes to increase both power output and lean mass.
Stomach cramping can occur when creatine is supplemented without sufficient water. Diarrhea and nausea can occur when too much creatine is supplemented at once, in which case doses should be spread out throughout the day and taken with meals. There have been some anecdotal reports of a subtle but noticeable stimulatory effect on alertness, but this may be a placebo effect.
There have been some anecdotal reports of restlessness when creatine is supplemented less than an hour before falling asleep. The water retention usually seen with higher loading doses can exceed five pounds more than two kilograms.
Lower doses may cause less water retention. While water mass is not muscle mass though both count as lean mass , prolonged creatine supplementation results in an increased rate of muscle growth. Hyperhydration strategies creatine plus glycerol appear inefficacious as drug-masking strategies. Alpha-Lipoic Acid see here. Leucine , due to mTOR activation see here. HMB see here , a metabolite of leucine.
There are many different forms of creatine available on the market, but creatine monohydrate is the cheapest and most effective. Another option is micronized creatine monohydrate, which dissolves in water more easily and can be more practical.
Creatine monohydrate can be supplemented through a loading protocol. To start loading, take 0. Diarrhea and nausea can occur when too much creatine is supplemented at once, in which case doses should be spread out over the day and taken with meals. There do exist deficiency symptoms that result in mental retardation. Creatine is quite well-studied, and seems safe and effective in enhancing some aspects of performance. Do you need to cycle creatine? Read full answer to "Do you need to cycle creatine?
Is creatine a steroid? No; not at all. It bears no relation to a steroid structurally or in its actions. Read full answer to "Is creatine a steroid? What happens if I go off of creatine? Read full answer to "What happens if I go off of creatine?
Can creatine cause cancer? Read full answer to "Can creatine cause cancer? Read full answer to "Is creatine safe? Does caffeine counteract creatine? Read full answer to "Does caffeine counteract creatine? When should I take creatine? Read full answer to "When should I take creatine? Do I need to load creatine? It is not needed, it can be used as diagnosis to see if you 'respond' to creatine or to get slightly quicker benefits but in the long run loading is not a requirement of creatine supplementation.
No harm in it either, except perhaps digestive discomfort Read full answer to "Do I need to load creatine? Does creatine benefit elite athletes? Creatine benefits all exercise for all individuals when it is strength based.
However, this benefit does appear to be less noticeable to elite athletes than it does to novice athletes. Read full answer to "Does creatine benefit elite athletes? What is the best form of creatine? The best form of creatine is basic Creatine Monohydrate , which is the cheapest, yet on par with many other forms. No other form has enough evidence to claim it is better than Monohydrate. Read full answer to "What is the best form of creatine? What is creatine nitrate? Creatine nitrate is simply a more water-soluble version of creatine.
It is not more potent than regular creatine monohydrate. Read full answer to "What is creatine nitrate? Does creatine cause kidney problems? Studies looking at creatine and the kidneys have failed to demonstrate any harm from supplementation except for some plausible interactions with diuretic pharmaceuticals.
Read full answer to "Does creatine cause kidney problems? What beneficial compounds are primarily found in animal products? Read full answer to "What beneficial compounds are primarily found in animal products?
Does creatine cause hair loss? Read full answer to "Does creatine cause hair loss? Can creatine increase your testosterone levels? There is no convincing evidence that creatine can increase your testosterone levels. Read full answer to "Can creatine increase your testosterone levels? The Human Effect Matrix looks at human studies it excludes animal and in vitro studies to tell you what effects creatine has on your body, and how strong these effects are. Creatine phosphate phosphocreatine functions as a phosphate reservoir.
Beef, with minimal visible connective tissue: Creatine from food is digested slower than creatine taken as a supplement, but total bioavailability is identical. Creatine is a small peptide — a structure composed of amino acids. Specifically, creatine is composed of L-arginine , glycine , and methionine.
Its molecular structure is depicted below. Depending on the cooking temperature and the presence of a reducing sugar, such as glycogen, carnosine and aspartic acid will degrade into acrylic acid and acrylamides. Creatine can also be converted to the biologically inactive creatinine through the removal of a water molecule. Finally, creatine can also participate in the formation of heterocyclic amines,  a process that can be partially inhibited by marination. Carbohydrates provide quick energy in an anaerobic environment high-intensity exercise , while fats provide sustained energy during periods of high oxygen availability low-intensity exercise or rest.
The breakdown of carbohydrates, fats, and ketones produces ATP adenosine triphosphate. By increasing the overall pool of cellular phosphocreatine, creatine supplementation can accelerate the reycling of ADP into ATP.
Since ATP stores are rapidly depleted during intense muscular effort, one of the major benefits of creatine supplementation is its ability to regenerate ATP stores faster, which can promote increased strength and power output. Creatine storage capacity is limited, though it increases as muscle mass increases.
Without supplementation, creatine is formed primarily in the liver, with minor contributions from the pancreas and kidneys. The two amino acids, glycine and arginine , combine via the enzyme Arginine: Glycine amidinotransferase AGAT to form ornithine and guanidoacetate. This is the first of two steps in creatine synthesis, and although rare, any deficiency of this enzyme can result in mild mental retardation and muscular weakness. Guanidoacetate made by AGAT then receives a methyl donation from S-adenosyl methionine via the enzyme guanidinoacetate methyltransferase GAMT , which produces S-adenosylhomocysteine as a byproduct and creatine.
For the most part, the above reactions occur in the liver,  where most systemic creatine is synthesized, but the AGAT and GAMT enzymes have been located in lesser amounts in kidney and pancreatic tissue the extra-hepatic synthesis locales .
Neurons also possess the capability to synthesize their own creatine. As mentioned above, S-adenylmethionine must be converted to S-adenylhomocysteine in order for guanidoacetate to convert into creatine, during a process known as methylation. Creatine supplementation alleviates the intrinsic burden of producing creatine. Supplementation reduces the expected increase in homocysteine  after intense exercise and may be a reason why creatine is seen as cardioprotective around the time of exercise.
Creatine is stored in the body in the form of creatine and as creatine phosphate, otherwise known as phosphocreatine, which is the creatine molecule bound to a phosphate group. Creatine kinase enzymes of which there are numerous isozymes exist in both the mitochondria and the cytosol of the cell.
Supplementation of creatine monohydrate increases stores of both of these compounds in myocytes, neurons, eyes, kidneys and testes. Increasing cellular survival preventing ATP depletion allows cells to survive longer against hypoxia, oxidative damage, and some toxins that damage neurons and skeletal muscle cells is a mechanism of creatine supplementation mediated via creatine-kinase.
Expressing the creatine-kinase enzyme in cells that do not normally express it and thus enabling these cells to use creatine exerts protective effects,  while inhibiting this enzyme reduces survival rates.
Creatine kinase appears to be subject to sexual dimorphism, meaning differences exist in males and females, with males exhibiting increased enzyme activity. Black people appear to have higher activity of the creatine kinase system compared to both white and hispanic people, with hispanic people having greater levels than whites.
When splitting a sample into exercisers and non-exercisers, it appears that exercise as a pre-requisite precedes a higher range of activity. Inactive people tend to be on the lower end of creatine kinase activity and relatively clustered in magnitude, while exercise generally increases activity, but also introduces a larger range of possible activity. Creatine is also a neurological nutrient.
People who cannot produce endogenous creatine suffer from a form of mental retardation with autistic-like symptoms due to deficiencies in the enzymes of creatine synthesis AGAT or GAMT. The main storage area of creatine in the human body is the skeletal contractile muscle, which holds true for other animals.
Therefore, consumption of skeletal muscle meat products is the main human dietary source of creatine. Since vegetarians and vegans lack the main source of dietary creatine intake, which has been estimated to supply half of the daily requirements of creatine in normal people, both vegetarians and vegans have been reported to have lower levels of creatine. Due to this relative deficiency-state in vegetarians and vegans, some aspects of creatine supplementation are seen as more akin to normalizing a deficiency, rather than providing the benefits of supplementation.
In young vegetarians, but not omnivores, creatine supplementation can enhance cognition. Creatine monohydrate is the most common form of creatine, and if not otherwise mentioned is the default form of creatine used in most studies on creatine. This allows more creatine to be present in a concentrated formula, like capsules. In regard to supplementation, it is equivalent to creatine monohydrate.
Creatine hydrochloride Creatine HCl is a form of creatine characterized by the molecule being bound to a hydrochloric acid moiety. It is claimed to require a lower dosage than creatine monohydrate, but this claim has not been tested. Creatine hydrochloride likely forms into free creatine and free hydrochloric acid in the aqueous environment of the stomach, which would mean it is approximately bioequivalent to creatine monohydrate.
Liquid creatine has been shown to be less effective than creatine monohydrate. Buffered creatine Kre-Alkylyn is the brand name is touted to enhance the effects of creatine monohydrate due to a higher pH level, which enables better translocation across the cytoplasmic membrane and more accumulation in muscle tissues. This claim has not been demonstrated at this time, and a recent comparative study of buffered creatine against basic creatine monohydrate found no significant differences between the two in 36 resistance trained individuals, in regard to the effects or the accumulation of creatine in muscle tissue.
Creatine ethyl ester increases muscle levels of creatine to a lesser degree than creatine monohydrate. Creatine ethyl ester is more a pronutrient for creatinine rather than creatine,  and was originally created in an attempt to bypass the creatine transporter.
It is currently being studied for its potential as a treatment for situations in which there is a lack of creatine transporters alongside cyclocreatine as another possible example. Direct studies on creatine ethyl ester show it to be less effective than creatine monohydrate, on par with a placebo. Creatine ethyl ester is Magnesium-chelated creatine typically exerts the same ergogenic effects as creatine monohydrate at low doses. Creatine nitrate is a form of creatine in which a nitrate NO3 moiety is bound to the creatine molecule, which has been demonstrated to enhance solubility in water by approximately fold, with the pH of 2.
Creatine citrate is creatine bound to citric acid, or citrate. Creatine citrate does not differ greatly from monohydrate in regard to absorption or kinetics. The increased water solubility may play a factor in palatability.
It can be found in varying ratios of creatine: Creatine malate is the creatine molecule bound to malic acid. There might be some ergogenic benefits from malic acid on its own,  but this has not been investigated in conjunction with creatine.
Creatine pyruvate also known as creatine 2-oxopropanoate in an isomolar dose relative to creatine monohydrate has been shown to produce higher plasma levels of creatine peak and AUC with no discernible differences in absorption or excretion values. Polyethylene glycosylated creatine seems to be as effective as creatine monohydrate at a lower dose 1.
Creatine gluconate is a form of creatine supplementation in which the creatine molecule is bound to a glucose molecule. It currently does not have any studies conducted on it. Cyclocreatine 1-carboxymethyliminoimidazolidine is a synthetic analogue of creatine in a cyclic form.
It serves as a substrate for the creatine kinase enzyme system, acting as a creatine mimetic. The structure of cyclocreatine is fairly flat planar , which aids in passive diffusion across membranes. It has been used with success in an animal study, where mice suffered from a SLC6A8 creatine transporter at the blood brain barrier deficiency, which is not responsive to standard creatine supplementation. This increased permeability is noted in glioma cells, where it exerts anti-cancer effects related to cell swelling,   and in other membranes, such as breast cancer cells  and skeletal contractile muscle cells.
In regard to bioenergetics, phosphorylated cyclocreatine appears to have less affinity for the creatine kinase enzyme than phosphorylated creatine in terms of donating the high energy phosphate group about fold less affinity despite the process of receiving phosphorylation being similar. When creatine is absorbed it pulls water in with it, causing cells to swell.
Glycogen synthesis is known to respond directly and positively to cellular swelling. Inducing hypertonicity a reduction in cellular swelling is known to actually increase the mRNA of the creatine transporter,  thought to be due to increasing cellular creatine uptake to normalize creatine levels. This has been noted in both muscle cells and endothelial cells, but is thought to apply to all cells. This regulation of creatine uptake is similar to other osmolytic agents such as myo - inositol or taurine , which have their uptake into cells enhanced during periods of hypertonia in order to increase cellular swelling.
Phosphocreatine, the higher energy form of creatine, can associate with and protect cell membranes. In a later study, it was found that biologically relevant concentrations mM of creatine bind synthetic membranes with lipid compositions mimicking the inner mitochondrial membrane or plasma membrane in a concentration-dependent manner.
This also conferred a degree of protection, increasing membrane stability in response to challenge from a number of destabilizing agents. Phosphocreatine was more effective than creatine in this context, although both were able to bind and stabilize membranes. Cyclocreatine an analogue of creatine has been shown to protect microtubules in a cell and protect its structure, but it is not known whether these benefits can be expanded to creatine.
Creatine is involved indirectly in whole body methylation processes. This is due to creatine synthesis having a relatively large methyl cost, as the creatine precursor known as guanidinoacetate GAA requires a methyl donation from S-adenosyl methionine SAMe in order to produce creatine. This may require up to half of the methyl groups available in the human body. SAMe is the primary methyl donor in the human body, and supplements that preserve SAMe such as trimethylglycine ; TMG promote a variety of benefits in the human body, like a reduction in homocysteine and reduced risk of fatty liver.
Creatine has been implicated in both reducing homocysteine  and preventing fatty liver in rodents  , thought to be secondary to preserving SAMe. Creatine supplementation may be able to enhance lifespan, secondary to increasing intracellular carnosine stores. Carnosine is the metabolic compound formed from beta-alanine supplementation, and in a mouse-model for premature aging senescence-accelerated premature aging, SAMP8 creatine supplementation without any beta-alanine has been shown to increase cellular carnosine stores.
However, creatinine was noted to increase in the presence of pancreatin, a mixture of pancreatic enzymes. The specific mechanism of intestinal uptake for creatine is not clear, although transporters have been identified in rat jujenum, and confirmed at the mRNA level in humans.
There is also evidence to suggest that increased ingestion of creatine leads to an increased fecal creatine value, suggesting that the intestinal uptake can be saturated. Researchers observed that it took 2. SLC6A8 is encoded by the gene present on the Xq28 region of the human X-chromosome and is expressed in most tissues.
Creatine transport has been shown to increase when muscle creatine stores are depleted. This was only noted to occur in muscle with particular fiber types soleus and red gastrocnemius , while other fiber types, such as white grastrocnemius, did not show any clear trend.
In muscle cells, the creatine transporter is predominantly localized to the sarcolemmal membrane. People who get a sufficiently high influx of creatine are known as responders. Creatine is only taken up by its transporter, and changes in the activity level of this transporter are wholly causative of changes in creatine uptake. The transporter is regulated by mostly cytosolic factors as well as some external factors that affect creatine transport activity,  including extracellular creatine.
The creatine transporter CrT is positively regulated by proteins known to be involved in sensing and responding to the cellular energy state, including the mammalian target of rapamycin mTOR . Some other cytokines and hormones may increase the receptor activity. These include growth hormone GH which acts upon the growth hormone receptor GHR   to stimulate c-Src   which directly increases the activity of the CrT via phosphorylation.
Finally, starvation nutrient deprivation for four days appears to increase activity of the creatine transporter secondary to decreasing serine phosphorylation SGK target  with no influence on tyrosine phosphorylation c-Src target. In vitro , insulin promotes creatine uptake in mouse  and human muscle cells. Negative regulators of the creatine transporter CrT are those that, when activated, reduce the activity of the CrT and overall creatine uptake into cells.
Although indirect, activation of AMPK has been noted to reduce the V max of the CrT without altering creatine binding, and is involved in internalizing the receptors. In contrast to kidney epithelial cells, others have reported that creatine transport is increased by AMPK in the heart,  indicating that CrT is likely regulated in a cell-and tissue specific manner in response to local energy demands. Composition of lipids in human serum and adipose tissue during prolonged feeding of a diet high in unsaturated fat.
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Applied and Environmental Microbiology Nov;71 Increased consumption of refined carbohydrates and the epidemic of type 2 diabetes in the United States: Low-fat dietary pattern and risk of colorectal cancer: Hat tip Melissa McEwen, The human colon in evolution: Archives of Internal Medicine Jun 27; Late-life alcohol consumption and year mortality.
Clinical and Experimental Research Nov;34 Hat tip to Robin Hanson: Alcohol is healthy, September 2, , www. Alcohol dosing and total mortality in men and women: Archives of Internal Medicine Dec 11—25; Camargo CA et al.
Prospective study of moderate alcohol consumption and mortality in US male physicians. Archives of Internal Medicine Jan 13; 1: Yuan JM et al.
Follow up study of moderate alcohol intake and mortality among middle aged men in Shanghai, China. BMJ Jan 4; Doll R et al.
Mortality in relation to consumption of alcohol: BMJ Oct 8; Hat tip to David J. Alcohol problems and solutions, www2. Alcohol consumption and mortality. Characteristics of drinking groups. Wann sollte man fettig essen? Athleten-Interview - Maud Maria Descheemaeker. Christian Kellenberger - Der Weg ist das Ziel. Athleten Interview - Eve Lewis. Athleten-Interview mit Jürgen Reis - Part 1. Die Wahrheit über Kohlenhydrate. Auch ein schöner Rücken kann entzücken.
Die Bedeutung der Muskelreife. Cardio Training das notwendige Übel. Lebensmittel für vor und nach dem Training. Casein - ein Milchprotein aus frischer Kuhmilch. Alles über Molke Inhaltsstoffe im Fokus. Neues aus Hajos Fitnessküche. Der Natural Shake für Hardgainer.
Out-of-Season-Test beim Deutschen Meister. Short News - Sommer