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In vivo gluten ingestion in coeliac disease. See also Bodybuilding Bodyweight exercise Calisthenics Weightlifting Plyometrics Weight training List of exercises Gym Legend c - compound exercise, i - isolated exercise. This section does not cite any sources. However, I would expect similar TEF from whey protein vs beef protein isolate, for example. The adipostat balloon, October 12, , http: Phosphocreatine releases energy to aid cellular function during stress. Older people who exercise against a resistance or force become stronger.


The Ultimate Guide to Muscle Protein Synthesis

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Am J Clin Nutr Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Brain Res Bull Neurotransmitter precursors for the treatment of depression. Neurotransmitter precursor amino acids in the treatment of multi-infarct dementia and Alzheimer's disease.

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Anti-cancer effects have been observed with the creatine analogue cyclocreatine [] [] [] and have been replicated with creatine itself. These effects tend to be a reduction in which the rate of implanted tumors progresses. These anti-cancer effects do not have a known reliability, as the expression of creatine kinase varies widely based on the type of tumor.

In regard to genetic damage, creatine has been shown in vitro to reduce mitochondrial DNA damage, secondary to buffering stores of ATP. Creatine supplementation appears to augment the anti-cancer effects of Vitamin C and methylglyoxal, [] a metabolic by-product of glycolysis. Creatine is known to be present in the retina due to the expression of creatine kinase CK [] [40] and the GAMT enzyme of creatine synthesis, which is also present in the mammalian retina.

Creatine is known to occur in highly concetrated levels in chicken photoreceptors, relative to other parts of the eye mM [] alongside high levels of creatine kinase. The glial cells in the retina Müller cells, known to supply photoreceptors with lactate for nutrition [] do not appear to possess any creatine transporters [] although they appear to express AGAT [] , GAMT, [] and can synthesize creatine for the retina. There is a genetic condition known as gyrate atrophy of the choroid and retina , which is associated with a high level of Ornithine in the blood and a relative decrease in Arginine , which causes a relative creatine deficiency due to L-arginine being required to make creatine [] [] and because high ornithine can suppress creatine synthesis AGAT in the glial cells of the retina.

Elsewhere, it has been noted that in chronic progressive external ophthalmoplegia CPEO, a progressive weakening of the muscles around the eye and a mitochondrial disorder , there was a failure of creatine supplementation to benefit symptoms when subjects were provided 20g daily for four weeks. Epithelial cells taken from the respiratory tract nasal, tracheal, and bronchial express very low levels of creatine kinase and phosphocreatine.

The addition of 15mM creatine to the medium does not appear to alter their growth or function. The pancreas is one of the extrahepatic beyond the liver organs that can synthesize creatine, alongside the kidneys. Creatine is mostly synthesized in the liver via AGAT and GAMT [29] [33] the other locations are neurons, [35] the pancreas, and kidneys [34] despite it not being stored in high levels in the liver like glycogen or adipose would be.

Supplemental creatine is known to suppress AGAT by downregulating transcription, [31] which probably occurs in humans since the products of AGAT are reduced with creatine supplementation. These protective effects are similar to those seen with trimethylglycine , since they both cause an increase in liver concentrations of phosphatidylcholine PC, causing an increase in vLDL production and efflux of triglycerides from the liver. Young adult athletes who reported creatine usage for over two years prior to the study retrospective design were not significantly different than controls.

The kidneys are known to express a secondary creatine transporter known as the monocarboxylate transporter 12 MCT12, also known as SLC16A12 similar to the retina. In otherwise normal animals, supplementation of creatine at 0.

Nephrectomized rats may have significantly reduced creatine synthesis rates [] via impairment of methylation the GAMT enzyme [] although creatine reuptake from the urine seems unimpaired. When looking specifically at human studies, there has been a failure of creatine supplementation to induce or exacerbate kidney damage in people with ALS.

Creatine concentration is normally increased in the placenta and brain in the midgestation phase until term, with further increases in the brain for another two weeks after birth. Injections of creatine are known to be neuroprotective against low oxygen levels hypoxia even to neonatal rats. Skin degradation is caused by a loss of collagen and degradation of the extracellular matrix, [] which is enhanced by UV radiation produces reactive oxygen species which stimulate MMPs [] and contributes to skin integrity loss and wrinkling.

Due to the stimulation of collagen being associated with a cellular surplus of energy [] and intracellular stores of energy declining with age, [] [] creatine has been investigated as a topical anti-aging agent. The increased cellular storage of creatine may also confer antioxidative effects secondary to enhancing mitochondrial function [] and may play a preventative role in addition to having a rehabilitative effect.

A study using creatine at 0. In advanced cases of ALS, the main cause of death is respiratory failure stemming from an inability to control the intercostal muscles. Some studies have failed to find improvements in MVIC in regard to attenuating the decline over time with 10g daily over 16 months, [] with 5g daily after a five day loading phase for six months, [] and 5g daily over nine months.

One study lasting 16 months using 10g creatine daily alongside the pharmaceutical riluzole noted that, after 34 of the patients died from ALS, creatine failed to exert protective effects against ALS-related mortality adjusted hazard ratio of 0.

A smaller study measuring only eight deaths noted that the six in placebo relative to two in creatine was too small of a sample size to detect a statistically significant difference. The first open label trial on ALS failed to significantly alter lung function as assessed by FEV when comparing the rate of decline pretreatment relative to treatment.

Mitochondrial myopathies are a subgroup of mitochondrial cytopathies in which the skeletal muscle is negatively influenced. They are characterized by weaknesses in muscular function and energy metabolism. A loading phase of 10g creatine monohydrate for two weeks and 4g for the final week in subjects with MELAS Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes has been noted to increase physical strength relative to baseline, although the poor VO 2 max seen in these subjects was not affected.

It is an X-linked progressive myopathy associated with abnormalities in the dystrophin gene. While the trend toward whole body strength reduction seen in placebo was ablated and there was no interaction with corticosteroids, [] this study failed to find an influence on activities of daily living or lung function. There is no cure for either because they are genetic disorders, so current therapies are aimed at reducing side-effects.

Therapies include modafinil for the somnolence [] and perhaps creatine for the reduction in strength and functionality.

Creatine is thought to be therapeutic due to a pilot study on an assortment of neuromuscular diseases 91 patients in total, 15 of which had congenital myotonias during which there was an overall increase in strength. In patients with DM1 given a short loading phase Elsewhere, a pilot study in people who met the diagnostic criteria for myotonic dystrophy type 2 DM2 or PROMM given 10g of creatine daily for three months failed to find an increase in strength, but there appeared to be a significant improvement in subjective wellbeing reported by the patients, relative to placebo.

The failure of creatine to improve physical performance in these conditions is thought to be related to the myopathies in general, which are known to result in less phosphocreatine in skeletal muscle, [] associated with reduced expression of the creatine transporter. Creatine supplementation is being explored as a treatment for sarcopenia, the passive loss of lean mass that occurs with aging.

In a pilot study on youth with cystic fibrosis, supplementation of creatine at 12g for a week and 6g for eleven weeks afterward was associated with a time-dependent increase in maximal isometric strength reaching In people with COPD given either glucose placebo Due to its antidepressive properties, creatine supplementation has been investigated in people with bipolar disorder, despite creatine levels in the brains of bipolar patients not being significantly different than controls, [] [] although the activity of creatine kinase seems to reflect the state of manic or depressive symptoms.

Insulin secretion seems to have interplay with creatine supplementation. However, this is only clinically significant during the first few days of loading, when myocyte stores of creatine are depleted.

During a creatine loading phase, it is possible for insulin secretion to enhance the rate of uptake into myocytes. When the myocytes are saturated with creatine seen after 3 days of loading , then this insulin effect seems to disappear. In vitro studies on endothelial cells have noted that the benefits of creatine against atherosclerosis via immune cell adhesion to the endothelial cell are blocked with the pharmaceutical ZM, a high affintiy adenosine A 2A receptor antagonist.

Thus, the study may have been underpowered or done in too short a time frame the test was done after only 5 days of loading to observe any possible effects. However, caffeine does not negate the benefits of creatine loading when not coingested, but just taken before exercise in the same dosage. It is not synergystic, although the metabolism of the two are linked. Trimethylglycine TMG, betaine is a dietary supplement and component of beet root , which is a methyl donor.

It contributes to metabolic processes in the body which require a methyl group either directly the methylation of homocysteine or indirectly via replenishing the active form of folate or via replenishing S-adenosyl methionine SAMe. As the synthesis of creatine via GAMT requires a donation from SAMe, [] it is thought that TMG can aid in creatine synthesis, which has been noted in the rat liver in the absence of creatine supplementation.

The one study to investigate this claim noted that the addition of 2g of supplemental TMG to 20g supplemental creatine failed to outperform creatine by itself in terms of increasing muscular creatine stores or power output. In a study on Alpha-Lipoic Acid , 1,mg of ALA paired with g sucrose and 20g creatine monohydrate was more effective in increasing muscular creatine levels relative to creatine alone and creatine combined with sucrose.

A study in swine noted increased water retention via a PY value in the group fed both creatine and alpha-lipoic acid [] at a dose of 24g and mg daily, respectively. COX-2, a pro-inflammatory enzyme, is sometimes a therapeutic target for both muscle soreness and some degenerative diseases that are exacerbated by inflammation.

There are no clinically significant side effects of acute creatine supplementation. Numerous trials have been conducted in humans with varying dosages, and the side effects have been limited to gastrointestinal distress from too much creatine consumption at once and cramping from insufficient hydration.

Studies that use a dosage range typical of creatine supplementation in the range of 5g a day following an acute loading period note increases to total body water of 6. In regard to the loading period, two reviews suggest that the range of weight gain associated with creatine supplementation at 20g for 7 days is in the range of 0.

Studies measuring extracellular water versus intracellular water note similar increases in both, associated with creatine. Creatine does not tend to disturb the ratios of water to dry mass in various tissues measured. One case study exists of a man with focal segmental glomerulosclerosis who experienced an accelerated rate of GFR decline during supplementation 5g thrice daily for loading, then a 2g maintenance for seven weeks which was partially reversed upon supplement cessation.

This was deemed strong circumstantial evidence, and the brand of supplement was not named. One case study exists in which a man with a single damaged kidney low GFR supplemented creatine at 20g for a period of five days and then a maintenance period for 30 days.

Supplementation failed to cause any kidney damage, despite the subject eating a diet very high in protein 2. Creat ine is normally metabolized into creat inine note the difference in spelling , which is eliminated by the kidneys under normal conditions.

Creatinine is easy to measure and as such it is a biomarker of kidney damage. Low dose creatine may not cause alterations in this biomarker in otherwise normal adults [] [] [] but high doses of supplemental creatine may cause a false positive an increase in creatinine, due to creatine turning into creatinine, which does not signify kidney damage and is a diagnostic error. Common misspellings for Creatine include creatin, craetine, creating, creetine, createen.

Please click here if you are not redirected within a few seconds. This page is regularly updated, to include the most recently available clinical trial evidence.

History Research analysis by Kamal Patel and verified by the Examine. Last updated on Jun 25, Also Known As creatine monohydrate, creatine 2-oxopropanoate, a-methylguanidinoacetic acid Do Not Confuse With creatinine metabolite , cyclocreatine analogue , creatinol O-phosphate analogue Things to Note There have been some anecdotal reports of a subtle but noticeable stimulatory effect on alertness, but this may be a placebo effect.

Grade Level of Evidence Robust research conducted with repeated double-blind clinical trials Multiple studies where at least two are double-blind and placebo controlled Single double-blind study or multiple cohort studies Uncontrolled or observational studies only.

The amount of high quality evidence. The more evidence, the more we can trust the results. The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect. Scientific research does not always agree. Creatine supplementation is the reference compound for increasing muscular creatine levels; there is variability in this increase, however, with some nonresponders.

Appears to have a large effect on increasing overall weight due to water retention in persons who respond to creatine supplementation. Degree of increase is variable. Creatine supplementation usually increases serum creatinine levels during the loading phase but usually not during maintenance , since creatinine is the breakdown product of creatine. This is not indicative of kidney damage. Appears to be quite notable due to the increase in water weight in skeletal muscle tissue following creatine supplementation.

Appears to increase anaerobic cardiovascular capacity, not to a remarkable degree however. Does appear to have inherent lean mass building properties, but a large amount of research is confounded with water weight gains difficult to assess potency. In otherwise healthy persons given creatine supplementation, there is no significant beneficial nor negative influence on kidney function.

No reliable improvement in swimming performance. Fatigue is also reduced, though to a lesser degree, in cases of sleep deprivation. The influence of creatine on well being and general happiness is usually dependent on it treating a disease state; there does not appear to be a per se benefit to well being.

Degree of testosterone spike is not overly notable, although it appears to be present. Preliminary evidence seems to support a minor to moderate benefit with regard to Myotonic Dystrophy type II DM2 and a mild benefit or none with regard to DM1. Improvements in VO 2 max are not wholly reliable, and appear to be low in magnitude. Does not appear to confer any apparent benefit to prolonged cardiovascular exercise. No inherent benefit to omnivore cognition appears apparent, but it may benefit cognition in the sleep deprived.

Although there may be a small reduction of power output typical of creatine , the main parameter of interest cardiorespiratory output is mostly unaffected by creatine supplementation. The main parameter of interest with exercise in COPD cardiovascular capacity and aerobic exercise is wholly unaffected with supplementation, although power output still can be increased. Creatine reliably increases lean mass water at first, then muscle with more prolonged supplementation but does not appear to significantly alter fat mass.

No apparent reduction or increase in lactate in swimmers after sprinting exercises. No known influence on circulating liver enzymes, suggesting no liver toxicity in humans. No effect on healthy people or on disease states characterized by impaired lung function. Short term usage may increase power output like usual, but prolonged supplementation of creatine has failed to alter the deterioration of muscle and lung function.

While no reduction in mortality has been noted statistically, two studies have noted a trend towards reductions in mortality suggesting an unknown protective effect. No effect on cardiovascular exercise performance and lung and heart functions, the main parameters of concern when treating COPD. Depression symptoms seem to improve noticeably. This improvement is probably related to serotonin creatine supplementation appears to enhance SSRI therapy.

Possible gender differences a greater efficacy in females require further study. Degree of improvement is somewhat more potent than other supplemental options, and may be related to the improvements in glycemic control seen with creatine. During exercise, creatine supplementation can suppress growth hormone secretion: This bidirectional effect is similar to that of arginine supplementation.

Appears to be reliable in increasing cognition in vegetarians, but is based on limited evidence and not yet compared to a reference drug. An increase in DHT independent of an increase in testosterone has been noted, but the study requires replication due to some potential issues its location, the lack of biological plausibility, etc.

Creatine supplementation appears to reduce exercise-induced DNA damage. This is potentially promising with regard to cancer prevention. The effect of creatine supplementation on DNA methylation cannot be properly assessed due to a lack of comparisons with other agents.

Possibly an effect, but the less reliable effects of creatine in the older population which seem to respond less seems to manifest here. Appears to be somewhat effective in diabetics for improving glycemic control. Decrease in homocysteine biomarker of inflammatory cardiovascular disease was present, but not to a remarkable magnitude.

Creatine supplementation appears to induce myonuclei proliferation, to a degree unknown relative to other agents. There appears to be a mild therapeutic effect of creatine supplementation g to boys with DMD, mostly related to an improvement in handgrip strength and body composition with some parent-rated improvements.

The cognitive dysfunction associated with prolonged sleep deprivation can be attenuated, to a small degree, with prior creatine loading. No significant alterations in plasma adrenaline are seen with creatine supplementation during sleep deprivation. No significant alterations in plasma dopamine are seen with creatine supplementation during sleep deprivation.

No significant alterations in plasma noradrenaline are seen with creatine supplementation during sleep deprivation. There is no significant influence on protein losses in the urine proteinuria. The study that noted a prevention of lean mass loss did not distinguish between water and muscle, while the study that measured muscle mass specifically failed to find a protective effect during limb immobilization.

There is insufficient evidence to support a rehabilitative role of creatine supplementation. Increases in alertness tend to be during sleep deprivation or stress, rather than outright increases in alertness.

One study has found that creatine can increase blood flow to the calf and leg when combined with resistance training in healthy men. Creatine alone was found to have no effect. One study, that needs to be replicated, noted a reduction in range of motion. An increase in well-being and muscular strength has been noted in youth, but the main parameters under investigation lung and chest symptoms seemed unaffected. Cite this page "Creatine," Examine. Link to This Close. Multiple studies where at least two are double-blind and placebo controlled.

Single double-blind study or multiple cohort studies. Uncontrolled or observational studies only. Very High See all 18 studies. Very High See all 66 studies. Very High See all 28 studies. Moderate See all 12 studies. Hydration Total Body Water. Very High See all 9 studies. High See all 19 studies. Very High See all 20 studies. Very High See all 13 studies. Moderate See all 17 studies. High See all 7 studies. Low See all 4 studies.

Low See all 3 studies. There is limited evidence in favor of improvements in bone mineral density. Moderate See all 8 studies. Small degree of fatigue reduction during exercise, but appears unreliable. Moderate See all 6 studies. Not overly protective, but there appears to be a degree of protection. High See all 3 studies. Moderate See all 11 studies. High See all 6 studies.

Treatment of Myotonic Dystrophy. Low See all 6 studies. Very High See all 7 studies. Very High See all 4 studies. Exercise Capacity with Heart Conditions. Very High See all 3 studies. Very High See all 5 studies. Insufficient evidence to support a role of creatine in increasing IGF High See all 4 studies. No effect on overall cholesterol levels in otherwise healthy males. Very High See all 6 studies.

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Hat tip to geoff

Ghee Composition and its Role in the Ketogenic Diet