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]

Key point: Past a certain number of sets, the marginal increases in protein synthesis NO LONGER outweigh the cost of doing more sets. If 8 sets of chest exercises produce 95% of possible muscle protein synthesis… then it makes very little sense to do ANOTHER 10 sets (like most chest workouts) to try and inch out the final 5% of stimulation. Those extra 10 sets are simply damaging your muscle unnecessarily and impairing your ability to recover.
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.
Creatine ingested through supplementation is transported into the cells exclusively by CreaT1. However, there is another creatine transporter Crea T2, which is primarily active and present in the testes [12]. Creatine uptake is regulated by various mechanisms, namely phosphorylation and glycosylation as well as extracellular and intracellular levels of creatine. Crea T1 has shown to be highly sensitive to the extracellular and intracellular levels being specifically activated when total creatine content inside the cell decreases [12]. It has also been observed that in addition to cytosolic creatine, the existence of a mitochondrial isoform of Crea T1 allows creatine to be transported into the mitochondria. Indicating another intra-mitochondrial pool of creatine, which seems to play an essential role in the phosphate-transport system from the mitochondria to the cytosol [13]. Myopathy patients have demonstrated reduced levels of total creatine and phosphocreatine as well as lower levels of CreaT1 protein, which is thought to be a major contributor to these decreased levels [14].

In regard to the blood brain barrier (BBB), which is a tightly woven mesh of non-fenestrated microcapillary endothelial cells (MCECs) that prevents passive diffusion of many water-soluble or large compounds into the brain, creatine can be taken into the brain via the SLC6A8 transporter.[192] In contrast, the creatine precursor (guanidinoacetate, or GAA) only appears to enter this transporter during creatine deficiency.[192] More creatine is taken up than effluxed, and more GAA is effluxed rather than taken up, suggesting that creatine utilization in the brain from blood-borne sources[192] is the major source of neural creatine.[193][192] However, “capable of passage” differs from “unregulated passage” and creatine appears to have tightly regulated entry into the brain in vivo[193]. After injecting rats with a large dose of creatine, creatine levels increased and plateaued at 70uM above baseline levels. These baseline levels are about 10mM, so this equates to an 0.7% increase when superloaded.[193] These kinetics may be a reason for the relative lack of neural effects of creatine supplementation in creatine sufficient populations.


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 14.3%, which was maintained after 12-24 weeks of supplement cessation (18.2% higher than baseline).[485] This study noted that more patients reported an increase in wellbeing (9 subjects, 50%) rather than a decrease (3, 17%) or nothing (6, 33%) and that there was no influence on chest or lung symptoms.[485]
Foundational supplements are often overlooked for building muscle, because they work behind the scenes. In actuality, foundational supplements are important to take for building muscle, because they assist with overall health and wellness and contribute to the effectiveness of other muscle building supplements.* Some of the top foundational supplements are:
In 1912, Harvard University researchers Otto Folin and Willey Glover Denis found evidence that ingesting creatine can dramatically boost the creatine content of the muscle.[5][non-primary source needed] In the late 1920s, after finding that the intramuscular stores of creatine can be increased by ingesting creatine in larger than normal amounts, scientists discovered creatine phosphate, and determined that creatine is a key player in the metabolism of skeletal muscle. The substance creatine is naturally formed in vertebrates.[6]

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,[597] it is thought that TMG can aid in creatine synthesis, which has been noted in the rat liver in the absence of creatine supplementation.[598]
I HATE that the resistance training community can be so tribal. I have been preaching to bodybuilders for years about the benefits of powerlifting, or Olympic lifting or kettlebells or even Crossfit style conditioning and many have been receptive. Learn from each other and achieve levels of fitness you simply could not have otherwise. Don’t brush off bodybuilding wisdom…it could be the missing factor in your program.
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Bodybuilders may supplement their diets with protein for reasons of convenience, lower cost (relative to meat and fish products), ease of preparation, and to avoid the concurrent consumption of carbohydrates and fats. Additionally, some argue that bodybuilders, by virtue of their unique training and goals, require higher-than-average quantities of protein to support maximal muscle growth.[19][20][21][22][23][24][25] However, there is no scientific consensus for bodybuilders to consume more protein than the recommended dietary allowance.[18][26] Protein supplements are sold in ready-to-drink shakes, bars, meal replacement products (see below), bites, oats, gels and powders. Protein powders are the most popular and may have flavoring added for palatability. The powder is usually mixed with water, milk or fruit juice and is generally consumed immediately before and after exercising or in place of a meal. The sources of protein are as follows and differ in protein quality depending on their amino acid profile and digestibility:


In your body, you can only store enough ATP for about 10 seconds of maximum exercise, this means that after those storages are depleted, it is up to your body to produce ATP to reach the demand your body is placing. [5] Creatine helps in the body by increasing stores of phosphocreatine which is the main ingredient used to create new ATP during intense exercise. By just supplementing creatine for 6 days, you can double your levels of creatine in your muscle storages, resulting in a higher capacity to create energy. [5]
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]
Kilduff, L. P., Georgiades, E., James, N., Minnion, R. H., Mitchell, M., Kingsmore, D., Hadjicharlambous, M., and Pitsiladis, Y. P. The effects of creatine supplementation on cardiovascular, metabolic, and thermoregulatory responses during exercise in the heat in endurance-trained humans. Int J Sport Nutr Exerc Metab 2004;14:443-460. View abstract.
Higher percieved effort during heat (or due to elevations in body heat) are thought to be mediated by either the serotonergic system (suppresses performance)[388] or the dopaminergic system (enhances performance),[389][234] and creatine is thought to be involved in percieved effort during heat training since it has been noted previously to interact with neurotransmission by enhancing both serotonergic[253] and dopaminergic[230] neurotransmission.
Parashos, S. A., Swearingen, C. J., Biglan, K. M., Bodis-Wollner, I., Liang, G. S., Ross, G. W., Tilley, B. C., and Shulman, L. M. Determinants of the timing of symptomatic treatment in early Parkinson disease: The National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) Experience. Arch Neurol. 2009;66:1099-1104. View abstract.

Many trainees like to cycle between the two methods in order to prevent the body from adapting (maintaining a progressive overload), possibly emphasizing whichever method more suits their goals; typically, a bodybuilder will aim at sarcoplasmic hypertrophy most of the time but may change to a myofibrillar hypertrophy kind of training temporarily in order to move past a plateau. However, no real evidence has been provided to show that trainees ever reach this plateau, and rather was more of a hype created from "muscular confusion".[clarification needed][citation needed]


Consuming sufficient high-quality protein is essential for building muscle. Current recommendations are to consume a minimum of 0.8g of protein for each kg of body weight, however, this is really only applicable to the average sedentary individual. Current evidence shows that to support muscle development, protein intake is the key, therefore the recommended 0.8g per kg should be increased to 1.5-2.0g of protein per kg of body weight. For an 80 kg individual, that would equate to 120-160 grams of protein per day.
Gualano, B., de, Salles Painelli, V, Roschel, H., Lugaresi, R., Dorea, E., Artioli, G. G., Lima, F. R., da Silva, M. E., Cunha, M. R., Seguro, A. C., Shimizu, M. H., Otaduy, M. C., Sapienza, M. T., da Costa, Leite C., Bonfa, E., and Lancha Junior, A. H. Creatine supplementation does not impair kidney function in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial. Eur.J.Appl.Physiol 2011;111:749-756. View abstract.
So it was popular then, but is it effective now? Just because something is popular doesn’t mean it works. In the case of creatine supplementation, however, you can be confident that increased muscle strength and less fatigue is possible. All thanks to a critical chemical reaction taking place in your muscle cells. Read on and learn how creatine works and why it lives up to that nostalgic ‘90s hype.

Today I want to share with you some quality advice on how to gain weight. Now I caution you that this is for the really skinny guy looking to really gain weight because they barely have any meat on their bones. I know what it is like when you feel like you eat all the time and have nothing to show for it. I have been there. I also understand the feelings that you feel when people start to resent you because you can eat whatever you want and not ever gain a pound. They don't realize that to skinny guys, this is a curse more than it is a blessing at times.
2-[carbamimidoyl(methyl)amino]acetic acid, Cr, Creatin, Creatina, Créatine, Créatine Anhydre, Creatine Anhydrous, Creatine Citrate, Créatine Citrate, Creatine Ethyl Ester, Créatine Ethyl Ester, Creatine Ethyl Ester HCl, Créatine Ethyl Ester HCl, Creatine Gluconate, Creatine Hydrochloride, Créatine Kré Alkaline, Creatine Malate, Créatine Malate, Creatine Monohydrate, Créatine Monohydrate, Créatine Monohydratée, Creatine Pyroglutamate, Créatine Pyroglutamate, Creatine Pyruvate, Créatine Pyruvate, Dicreatine Malate, Dicréatine Malate, Di-Creatine Malate, Éthyle Ester de Créatine, Glycine, Kreatin, Kre-Alkalyn Pyruvate, Malate de Tricréatine, N-(aminoiminométhyl)-N-Méthyl, N-(aminoiminomethyl)-N methyl glycine, N-amidinosarcosine, Phosphocreatine, Phosphocréatine, Tricreatine HCA, Tricréatine HCA, Tricreatine Malate, Tricréatine Malate.

Polyethylene glycol is a non-toxic, water-soluble polymer that is capable of enhancing the absorption of creatine and various other substances [66]. Polyethylene glycol can be bound with CM to form polyethylene glycosylated creatine. One study [67] found that 5 g/d for 28 days of polyethylene glycosylated creatine was capable of increasing 1RM bench press in 22 untrained young men but not for lower body strength or muscular power. Body weight also did not significantly change in the creatine group which may be of particular interest to athletes in weight categories that require upper body strength. Herda et al [68] analyzed the effects of 5 g of CM and two smaller doses of polyethylene glycosylated creatine (containing 1.25 g and 2.5 g of creatine) administered over 30 days on muscular strength, endurance, and power output in fifty-eight healthy men. CM produced a significantly greater improvement in mean power and body weight meanwhile both CM and polyethylene glycosylated form showed a significantly (p < 0.05) greater improvement for strength when compared with control group. These strength increases were similar even though the dose of creatine in the polyethylene glycosylated creatine groups was up to 75% less than that of CM. These results seem to indicate that the addition of polyethylene glycol could increase the absorption efficiency of creatine but further research is needed before a definitive recommendation can be reached.
There are several different available forms of creatine: creatine anhydrous which is creatine with the water molecule removed in order to increase the concentration of creatine to a greater amount than that found in CM. Creatine has been manufactured in salt form: creatine pyruvate, creatine citrate, creatine malate, creatine phosphate, magnesium creatine, creatine oroate, Kre Alkalyn (creatine with baking soda). Creatine can also be manufactured in an ester form. Creatine ethyl ester (hydrochloride) is an example of this, as is creatine gluconate which is creatine bound to glucose. Another form is creatine effervescent which is creatine citrate or CM with citric acid and bicarbonate. The citric acid and bicarbonate react to produce an effervescent effect. When mixed with water the creatine separates from its carrier leaving a neutrally charged creatine, allowing it to dissolve to a higher degree in water. Manufacturers claim that creatine effervescent has a longer and more stable life in solution. When di-creatine citrate effervescent was studied [59] for stability in solution it was found that the di-creatine citrate dissociates to citric acid and creatine in aqueous solutions which in turn forms CM and eventually crystallises out of the solution due to its low solubility. Some of the creatine may also convert to creatinine.
Creatine is an organic acid naturally occurring in the body that supplies energy to muscle cells for short bursts of energy (as required in lifting weights) via creatine phosphate replenishment of ATP. A number of scientific studies have shown that creatine can improve strength,[32] energy,[33] muscle mass, and recovery times. In addition, recent studies have also shown that creatine improves brain function.[34] and reduces mental fatigue.[35] Unlike steroids or other performance-enhancing drugs, creatine can be found naturally in many common foods such as herring, tuna, salmon, and beef.
Collectively the above investigations indicate that creatine supplementation can be an effective strategy to maintain total creatine pool during a rehabilitation period after injury as well as to attenuate muscle damage induced by a prolonged endurance training session. In addition, it seems that creatine can act as an effective antioxidant agent after more intense resistance training sessions.
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