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Extracellular creatine (creatine outside of a cell) appears to influence creatine uptake into a cell. It seems that prolonged and excessive levels of creatine actually suppress uptake (a form of negative regulation to prevent excessive influx).[180] In vitro studies in rat muscle cells have shown that including 1mM creatine into cell culture medium substantially reduces creatine uptake into cells. The inhibitory effect was partially negated by protein synthesis inhibitors, suggesting that high levels of creatine induce the expression of a protein that suppresses creatine transporter activity.[180] Similar findings were reported in a later study in cultured mouse myoblasts, which noted a 2.4-fold increase in intracellular creatine levels in the presence of the protein synthesis inhibitor cyclohexamide.[174]
The creatine transporter is a sodium[139][140] and chloride[141][142] dependent membrane-associated transporter that belongs to the Na+/Cl-dependent family of neurotransmitter transporters.[143] In muscle cells and most other cell types,[131][141] the isomer of the creatine transporter is known as SLC6A8 (solute carrier family 6, member 8). SLC6A8 is encoded by the gene present on the Xq28 region of the human X-chromosome and is expressed in most tissues.[144] A related gene encoding a creatine transporter variant has also been identified at 16p11.1 that is expressed exclusively in the testes.[145] These two transporters share 98% homology.[144][145]
In nonelite swimmers conducting an intermittent sprint protocol (Six 50m sprints every two minutes), supplementation of a creatine loading period was able to reduce the decrement in speed during the third sprint (2% decrement rather than a 5% decrement) but not the sixth sprint. There were no changes in plasma lactate or other biomarkers of fatigue.[396] When examining a single 50m sprint in amateur swimmers, a creatine loading period is able to reduce the time to complete the sprint by 4.6%, while it had no benefit for the 100m sprint.[397] When the loading phase was followed by three weeks maintenance in youth, there was no apparent benefit to sprint performance (50m sprint with five minutes rest followed by a 100m freestyle) despite benefits to a swim bench test (30s sprints with a five minute break in between).[398]
3) Relatively low cholesterol. This is one nutrition category that many people overlook with these supplements, but it's arguable one of the most important. Remember, if you're going to be downing 2 of these a day, you DON'T want to be maxing out your cholesterol intake. Luckily, this whey keeps it down to 30mg per scoop (which is about 10% of your daily intake). I've seen worse and ... full review

Whey, the liquid remaining after milk has been curdled and strained, is rapidly digested and absorbed and has a remarkable ability to stimulate muscle protein synthesis (Hayes & Cribb, 2008). Whey is available in three varieties — whey protein powder, whey protein concentrate, whey protein isolate — and all provide high levels of the essential and branched chain amino acids, vitamins and minerals.


Creatine supplementation (11.4g) with glycerol (1g/kg; per se effective[394][395]) and glucose (75g) in endurance runners in the heat appears to attenuate the increase in internal temperature associated with an increase in total body water of 0.71+/-0.42L, while performance (VO2 max and running economy) were unaffected over 30 minutes.[3] Creatine is effective without glycerol (20g daily with 140g of glucose polymer over a week),[346] again without an improvement in physical performance.
Brain injury. Early research shows that taking creatine by mouth daily for 7 days increases the ability to exercise by increasing lung function in people with a spinal cord injury. However, other research shows that creatine does not improve wrist muscle or hand function. Early research also shows that taking creatine by mouth daily for 6 months reduces amnesia following a traumatic brain injury in children.
This increased permeability is noted in glioma cells, where it exerts anti-cancer effects related to cell swelling,[99][100] and in other membranes, such as breast cancer cells[101] and skeletal (contractile) muscle cells.[102] The kinetics of cyclocreatine appear to be first-order,[101] with a relative Vmax of 90, Km of 25mM and a KD of 1.2mM.[103]
However, the basis of “take creatine after your workout” comes from a 2013 study published in the JISSN, which can be found here (open access too!). In this study, recreational male bodybuilders (19 men overall) were given five grams of creatine either before or after their workouts. They trained five days per week but were also directed to consume 5g on their rest days at any time they wanted. The workouts were fairly similar to most gym workouts, and the methodology (what they did and how they did it) suggests that the findings would apply to most weightlifters.
For several years, research studies have shown that adolescents concerned with both athletics and appearance are taking performance-enhancing supplements. A study by the American Academy of Pediatrics of middle-school and high-school students ages 10 to 18 years found creatine use in all grades 6 through 12. About 5.6% of the study participants and 44% of high-school senior athletes admitted taking creatine.

Kornblum, C., Schroder, R., Muller, K., Vorgerd, M., Eggers, J., Bogdanow, M., Papassotiropoulos, A., Fabian, K., Klockgether, T., and Zange, J. Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover study. Eur J Neurol 2005;12:300-309. View abstract.
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).[545] Creatine has elsewhere failed to benefit lung function at 5g daily for months relative to control[546] and failed to significantly attenuate the rate of lung function deterioration over 16 months at 10g daily[505] and 5g daily over nine months.[507]
You are encouraged to confirm information obtained from or through this website with other sources. Our content is not a substitute for qualified medical advice. The supplement summaries on this website may not include all the information pertinent to your use. Before starting a diet, taking new supplements, or beginning an exercise program, check with your doctor to clear any lifestyle changes. Only your doctor can determine what is right for you based on your medical history and prescriptions.
Spillane M, Schoch R, Cooke M, Harvey T, Greenwood M, Kreider R, Willoughby DS. The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels. J Int Soc Sports Nutr. 2009;6:6. doi: 10.1186/1550-2783-6-6. [PMC free article] [PubMed] [CrossRef]

^ Jump up to: a b c d Luckose F, Pandey MC, Radhakrishna K (2015). "Effects of amino acid derivatives on physical, mental, and physiological activities". Crit. Rev. Food Sci. Nutr. 55 (13): 1793–1807. doi:10.1080/10408398.2012.708368. PMID 24279396. HMB, a derivative of leucine, prevents muscle damage and increases muscle strength by reducing exercise-induced proteolysis in muscles and also helps in increasing lean body mass. ... The meta analysis studies and the individual studies conducted support the use of HMB as an effective aid to increase body strength, body composition, and to prevent muscle damage during resistance training.
Rice Protein: An alternative protein powder for muscle gain, rice protein is ideal for people who are lactose intolerant or have a milk allergy. As far as muscle gain and body composition when taken post-workout, this study showed that there was zero difference in outcomes when comparing taking whey protein and rice protein. So, if you prefer using rice protein, you can take it with confidence knowing that you’ll be able to achieve the same results you’d achieve if you were taking whey protein.
It is suggested [16,37] that another mechanism for the effect of creatine could be enhanced muscle glycogen accumulation and GLUT4 expression, when creatine supplementation is combined with a glycogen depleting exercise. Whereas it has been observed [38] that creatine supplementation alone does not enhance muscle glycogen storage. Hickner et al [15] observed positive effects of creatine supplementation for enhancing initial and maintaining a higher level of muscle glycogen during 2 hours of cycling. In general, it is accepted that glycogen depleting exercises, such as high intensity or long duration exercise should combine high carbohydrate diets with creatine supplementation to achieve heightened muscle glycogen stores [39].

Some other cytokines and hormones may increase the receptor activity. These include growth hormone (GH) which acts upon the growth hormone receptor (GHR)[166][167] to stimulate c-Src[168][169] which directly increases the activity of the CrT via phosphorylation. This is known to occur with the 55kDa version of c-Src but not the 70kDa version and requires CD59 alongside c-Src.[170]

In regard to practical interventions, concurrent glycogen loading has been noted to increase creatine stores by 37-46% regardless of whether the tissue was exercised prior to loading phase.[176] It is important to note, however, that creatine levels in response to the creatine loading protocol were compared in one glycogen-depleted leg to the contralateral control leg, which was not exercised.[176] This does not rule out a possible systemic exercise-driven increase in creatine uptake, and the increase in creatine noted above[176] was larger than typically seen with a loading protocol (usually in the 20-25% range). Consistent with an exercise-effect, others have reported that exercise itself increases creatine uptake into muscle, reporting 68% greater creatine uptake in an exercised limb, relative to 14% without exercise.[153]


He pointed to data sets in Mayo Clinic Proceedings that found resistance training reduced the risk of developing metabolic syndrome or hypercholesterolemia. “If you build muscle, even if you’re not aerobically active, you burn more energy because you have more muscle. This also helps prevent obesity and provide long-term benefits on various health outcomes.”
A: The literature supports roughly 0.8-1 gram per pound of bodyweight in young adults. Can you eat more? As long as you have healthy, functioning kidneys, yes. Will you receive any further physiological benefit from it? Most likely, no. Not only that, since our calories are set, if we choose to overconsume protein then we must reduce either carbohydrates and/or fat in order to keep caloric expenditure within our set range. Once protein needs are met (~0.8-1g/lb of bodyweight) you will likely see greater benefits from higher carbohydrate consumptions given the influence they have on anabolism and the anaerobic energy pathway. However, as I mentioned above, these recommendations will differ for older trainees given the blunted anabolic response from the ingestion of amino acids. 
Beach muscles and Olympic lifts draw more attention. But the many little stabilizer muscles around your shoulders, hips, and midsection — collectively the core — provide a strong foundation. Challenging the stability and mobility of these key muscles with medicine balls, physioballs, mini-bands, and rotational movements (lifting, chopping) pays huge dividends.
Spero Karas, MD, assistant professor of orthopaedics in the division of sports medicine at Emory University, says that testosterone, the male hormone responsible for muscle growth, maxes out between the ages of 16 and 18. It reaches a plateau during the 20s and then begins to decline. As a result, muscle building after the adolescent years can be challenging, he says. 

In general, muscle content of creatine tends to be elevated to 15-20% above baseline (more than 20mM increase) in response to oral supplementation. People who get a sufficiently high influx of creatine are known as responders.[150][151][152][153] A phenomena known as “creatine nonresponse” occurs when people have less than a 10mM influx of creatine into muscle after prolonged supplementation.[154] Quasi-responders (10-20mM increase) also exist.[154] Nonresponse is thought to explain instances where people do not benefit from creatine supplementation in trials, since some trials that find no significant effect do find one when only investigating people with high creatine responsiveness.[155] There are clear differences between those who respond and those who do not, in regard to physical performance.[156] People who are creatine responsive tend to be younger, have higher muscle mass and type II muscle fiber content, but this has no correlation with dietary protein intake.[154][157]


Cribb et al (2007) [29] observed greater improvements on 1RM, lean body mass, fiber cross sectional area and contractile protein in trained young males when resistance training was combined with a multi-nutrient supplement containing 0.1 g/kg/d of creatine, 1.5 g/kg/d of protein and carbohydrate compared with protein alone or a protein carbohydrate supplement without the creatine. These findings were novel because at the time no other research had noted such improvements in body composition at the cellular and sub cellular level in resistance trained participants supplementing with creatine. The amount of creatine consumed in the study by Cribb et al was greater than the amount typically reported in previous studies (a loading dose of around 20 g/d followed by a maintenance dose of 3-5 g/d is generally equivalent to approximately 0.3 g/kg/d and 0.03 g/kg/d respectively) and the length of the supplementation period or absence of resistance exercise may explain the observed transcriptional level changes that were absent in previous studies [30,31].
Remember, this is for the extreme skinny guy...But I want you to start hitting a buffet once a week. Try and position this eating frenzy after a hard workout so that the majority of calories get shuttled into the muscles which will really help you pack on those pounds and gain weight in the right places. Don't go too overboard, but this will train your body to 'accept' more food and it will increase your appetite in the days to come. Take advantage of this strategy.
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.[547] These particular myopathies are thought to benefit from creatine supplementation, since creatine can help with some of the dysregulated energy production.[548]
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 160-fold less affinity) despite the process of receiving phosphorylation being similar.[104][105] When fed to chickens, phosphorylated cyclocreatine can accumulate up to 60mM in skeletal muscle,[106] which suggests a sequestering of phosphate groups before equilibrium is reached.[105] Cyclocreatine still has the capacity to donate phosphate, however, as beta-adrenergic stimulated skeletal muscle (which depletes ATP and glycogen) exhibits an attenuation of glycogen depletion (indicative of preservation of ATP) with phosphocreatine.[102]
The US FDA reports 50,000 health problems a year due to dietary supplements [14] and these often involve bodybuilding supplements.[15] For example, the "natural" best-seller Craze, 2012's "New Supplement of the Year" by bodybuilding.com, widely sold in stores such as Walmart and Amazon, was found to contain N,alpha-Diethylphenylethylamine, a methamphetamine analog.[16] Other products by Matt Cahill have contained dangerous substances causing blindness or liver damage, and experts say that Cahill is emblematic for the whole industry.[17]
Some of these medications that can harm the kidneys include cyclosporine (Neoral, Sandimmune); aminoglycosides including amikacin (Amikin), gentamicin (Garamycin, Gentak, others), and tobramycin (Nebcin, others); nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen (Advil, Motrin, Nuprin, others), indomethacin (Indocin), naproxen (Aleve, Anaprox, Naprelan, Naprosyn), piroxicam (Feldene); and numerous others.
Based on the limited data on performance and safety, some authors have not identified any conclusions and do not recommend its consumption in regards to creatine supplementation in children and adolescents [52,54]. Conversely, according to the view of the ISSN [5], younger athletes should consider a creatine supplement under certain conditions: puberty is past and he/she is involved in serious competitive training; the athlete is eating a well-balanced caloric adequate diet; he/she as well as the parents approve and understand the truth concerning the effects of creatine supplementation; supplement protocols are supervised by qualified professionals; recommended doses must not be exceeded; quality supplements are administered.
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Few supplements have the solid scientific foundation that creatine has. Studies show that it's effective for 80 percent of those who use it. Since creatine is found naturally in meat, the more meat you eat, the less likely you'll need creatine supplementation. Vegetarians or those who rarely eat meat, however, can get huge boosts from most creatine supplements.

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. Deficiencies in GAMT are more severe (although equally rare) relative to AGAT, resulting in severe mental retardation and autism-like symptoms.[31]


Studies have deemed staying in the range of 3 to 5 g per day range for maintenance to be safe, and while higher levels have been tested under acute conditions without adverse effects, there isn’t sufficient evidence to determine long-term safety. (8) If you’re interested in upping your creatine consumption, you should work with your doctor or dietitian to make sure it's right for your goals and health history.
If you're a serious strength or physique athlete, you've surely heard that supplements can help you get the most from your intense training sessions and on-point diet. But which supplements? The market is overstuffed like a bodybuilder in a child's blazer! You might be tempted to wander through a digital forest of get-big blogs and personal guru websites, but unfortunately those places can often be rife with misinformation.
This cellular influx may also decrease protein oxidation rates, which leads to increases in nitrogen balance and indirectly increases muscle mass.[379] This lowering of protein oxidation is from signaling changes caused vicariously through cell swelling[380][381] and appears to upregulate 216 genes[378] in a range of 1.3 to 5-fold increases, with the largest increase seen in the protein involved in satellite cell recruitment, sphingosine kinase-1. Most importantly for muscle hypertrophy, the protein content of PKBa/Akt1, p38 MAPK, and ERK6 increased 2.8+/-1.2 fold.[378] Sixty-nine genes are also downregulated after creatine supplementation, to less notable degrees.
This basic form of creatine comes in two forms, one of which involves the removal of the monohydrate (which results in creatine anhydrous) that converts to creatine monohydrate in an aqueous environment,[66][67] but due to the exclusion of the monohydrate it is 100% creatine by weight despite creatine monohydrate being 88% creatine by weight, as the monohydrate is 12%. This allows more creatine to be present in a concentrated formula, like capsules.[68]
Cranking up the levels of testosterone within the body, XPI's Testosyn is formulated with 100% natural and powerful ingredients to build lean muscle, boost sex drive, and increase energy levels. Using a high-performance testosterone complex that contains D-Aspartic Acid, Fenusterols, and Tribulus Terrestris, this potent supplement will aid in the enhancement of each workout and promote free testosterone. Testosyn's ingredients have the ability to increase testosterone levels nearly twice as much as other products for more strength, mass, and sexual vigor. Keep Reading »
Creatine synthesis primarily occurs in the liver and kidneys.[2][16] On average, it is produced endogenously at an estimated rate of about 8.3 mmol or 1 gram per day in young adults.[16][17] Creatine is also obtained through the diet at a rate of about 1 gram per day from an omnivorous diet.[16][18] Most of the human body's total creatine and phosphocreatine stores are found in skeletal muscle, while the remainder is distributed in the blood, brain, and other tissues.[17][18]

Mercimek-Mahmutoglu, S., Stoeckler-Ipsiroglu, S., Adami, A., Appleton, R., Araujo, H. C., Duran, M., Ensenauer, R., Fernandez-Alvarez, E., Garcia, P., Grolik, C., Item, C. B., Leuzzi, V., Marquardt, I., Muhl, A., Saelke-Kellermann, R. A., Salomons, G. S., Schulze, A., Surtees, R., van der Knaap, M. S., Vasconcelos, R., Verhoeven, N. M., Vilarinho, L., Wilichowski, E., and Jakobs, C. GAMT deficiency: features, treatment, and outcome in an inborn error of creatine synthesis. Neurology 8-8-2006;67:480-484. View abstract.

Nephrotoxic drugs. Because taking high doses of creatine might harm your kidneys, there is concern about combining creatine with drugs that might damage the kidneys (nephrotoxic drugs). Potentially nephrotoxic drugs include nonsteroidal anti-inflammatory drug (NSAIDs) such as ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve, others), cyclosporine (Neoral, Sandimmune) and others.
A big clue is digestion. He does occasional cleanses. (“There’s no planes that week,” he said. “And no judgment at home.”) The slightest change in a muscle, just a stripe in a striation, is noticed. And while Heath does most workouts alone, he has a trainer, Hany Rambod, who is based in California. They see each other about once a month. In between, Heath sends photos and receives workout and dietary advice in return.
In regard to liver fat buildup (steatosis), which is normally associated with reduced availability of S-adenosyl methionine[495][496] and a suppression in expression of genes involved in fatty acid oxidation (PPARα and CPT1), creatine supplementation at 1% of the rat diet alongside a diet that induces fatty liver is able to fully prevent (and nonsignificantly reduce relative to the control given standard diets) the aforementioned changes and the state of steatosis, as well as changes in serum biomarkers (glucose and insulin) that accompany steatosis.[125] 
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