Three amino acids (glycine, arginine and methionine) and three enzymes (L-arginine:glycine amidinotransferase, guanidinoacetate methyltransferase and methionine adenosyltransferase) are required for creatine synthesis. The impact creatine synthesis has on glycine metabolism in adults is low, however the demand is more appreciable on the metabolism of arginine and methionine [11].

More recent studies on the regulation of CrT creatine transport activity have identified the protein kinase (Janus-Activating Kinase 2) JAK2, which suppresses the rate of creatine uptake via CrT without affecting creatine binding.[181] JAK2 is a regulatory protein involved in stabilizing the cellular membrane and controlling water concentrations in response to osmotic stress.[182][183] Similar to c-Src (a positive creatine transport regulator), Jak2 can also be activated by growth hormone signaling.[169][184] The growth hormone receptor seems to activate these two factors independently, as gh-mediated activation of c-Src does not require JAK2.[168] Given that c-Src is a positive regulator of CrT, JAK2 is a negative regulator, and the fact that downstream signals from both are induced by growth hormone, it is tempting to speculate that JAK2 activation downstream of the gh receptor may function as a homeostatic response to limit c-src induced creatine uptake. This has not been studied, however, and the effects of gh-induced JAK2 signaling on CrT activity have not been examined.


Using too much weight, too soon; always start lower than your expected ability and work your way up that first workout. If your form suffers, you are swinging the weight, or using momentum, this indicates you may be using too much weight. Greater momentum increases the potential for injury and reduces the effectiveness to the muscle group being targeted.
Overtraining occurs when a bodybuilder has trained to the point where his workload exceeds his recovery capacity. There are many reasons why overtraining occurs, including lack of adequate nutrition, lack of recovery time between workouts, insufficient sleep, and training at a high intensity for too long (a lack of splitting apart workouts). Training at a high intensity too frequently also stimulates the central nervous system (CNS) and can result in a hyperadrenergic state that interferes with sleep patterns.[51] To avoid overtraining, intense frequent training must be met with at least an equal amount of purposeful recovery. Timely provision of carbohydrates, proteins, and various micronutrients such as vitamins, minerals, phytochemicals, even nutritional supplements are acutely critical. A mental disorder informally called “bigorexia” (by analogy with anorexia) may be held accountable of some people overtraining. Sufferers feel as if they are never big enough or muscular enough, which forces them to overtrain in order to try and reach their goal physique.[52]
Of the three, protein will of course play the most important role in the muscle building process (like calories, it’s one our required “supplies”), although fat and carbs will still be important for other reasons which range from optimizing hormone production (e.g. testosterone, the muscle building hormone) to enhancing training performance and recovery.
Creatine supplementation has once been noted to improve wellbeing and fatigue resistance in people with DM2, but has twice failed for people with DM1. In all three studies, it has failed to improve power output. This is thought to be due to a reduction in the expression of the creatine transporter preventing an increase in muscular phosphocreatine content.
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.[616] Elsewhere, interstitial nephritis associated with creatine supplementation has been reported in a man, although symptoms arose four weeks after supplementation started with no evidence to support correlation.[617] Some studies involving athletes and various dietary supplements have attempted to draw a correlation with creatine and cases of rhabdomyolysis.[618][619][620][621] Finally, one study in a diabetic person ingesting both metformin and creatine resulting in metabolic acidosis has attempted to place causation on creatine, but it did not establish causation or circumstantial evidence.[622]
A double-blind study provided 20 g/day of creatine monohydrate for 5 days to qualified sprinters and jumpers who performed 45 seconds of continuous jumping and 60 seconds of continuous treadmill running. Supplementation enhanced performance in the jumping test by 7% for the first 15 seconds and 12% for the next 15 seconds, but there was no difference for the final 15 seconds. There was a 13% improvement in the time of intensive running to exhaustion [12].

Sports where strength training is central are bodybuilding, weightlifting, powerlifting, and strongman, highland games, hammer throw, shot put, discus throw, and javelin throw. Many other sports use strength training as part of their training regimen, notably: American football, baseball, basketball, football, hockey, lacrosse, mixed martial arts, rowing, rugby league, rugby union, track and field, boxing and wrestling.
Heath suggests incorporating dropsets into your training routine by immediately decreasing the weight and repping out again to failure. “Dropsets overload the muscle with shorter rest periods and increasing volume which you need to grow,” says Heath. “That overload improves your body’s abilities to utilize more nutrients, natural growth hormone, and natural testosterone into those areas and makes the supplements you take more effective.” Heath’s favorite way to do dropsets is on a pin-loaded machine since it’s faster to switch weights.
In muscle cells, the creatine transporter is predominantly localized to the sarcolemmal membrane. Western blot analysis of creatine transporter expression revealed the presence of two distinc protein bands, migrating at 55kDa and 70kDa on reducing SDS-PAGE gels.[147][148] The 73kDa band has been reported to be the predominant band in humans, with no differences based on gender.[148] A more recent report demonstrated that the 55kDa creatine transporter variant is glycosylated, forming the 73 kDa protein. Therefore, the 55 and 75kDa protein bands are actually immature and mature/processed forms of the creatine transporter protein, respectively.[149]
One of the studies noting a reduction in fatigue in healthy subjects given creatine (8g) for five days prior to a mathematical test noted a relative decrease in oxygenation hemoglobin in the brain and an increase in deoxygenated hemoglobin, which normally indicates a reduction in cerebral oxygenation.[245] The authors made note of how cytoplasmic phosphocreatine can increase oxygen uptake into cells (noted in vitro in a concentration dependent manner between 0-25mM[245]) and suggested that either cells were taking up more oxygen from hemoglobin, or that increased mitochondrial efficiency resulted in less of a need for oxygen.[245]
You’d have to look hard to find a fitness expert who doesn’t recommend taking supplemental protein powder for building muscle. It’s one of the best supplements for building muscle on the market! In addition to serving as a muscle building supplement, protein powder can be the perfect complement to a successful weight loss plan. Studies show that the supplement can prevent loss of muscle mass, helping you lose fat exclusively instead.
While creatine's influence on physical performance has been well documented since the early twentieth century, it came into public view following the 1992 Olympics in Barcelona. An August 7, 1992 article in The Times reported that Linford Christie, the gold medal winner at 100 meters, had used creatine before the Olympics. An article in Bodybuilding Monthly named Sally Gunnell, who was the gold medalist in the 400-meter hurdles, as another creatine user. In addition, The Times also noted that 100 meter hurdler Colin Jackson began taking creatine before the Olympics.[12][13]
A: At the end of the day, the most important variable regarding weight gain or loss is calorie consumption. However, meal frequency and timing around activity can both influence workout intensity and duration thus potentially allowing for further improvements in body composition. Remember, muscle growth isn’t a pulsatile process, it doesn’t just acutely spike and then return to baseline so if there aren’t circulating amino acids within the blood stream then they’ll have to be broken down from muscle as this is the highest form of concentrated amino acids within the body. That being said, it would probably be a good idea to consume anywhere from 3-6 meals spread throughout the day depending upon your schedule and preference. Ideally, we want to stimulate anabolism through food every 3-5 hours.

Objective: Are you getting stronger? Increasing either weight or reps? If you're measuring individual markers on a daily basis like vertical jump, grip strength, or resting heart rate then what sort of trends are you noticing in these variables? If they're staying the same while your strength is increasing, then you're recovering well. If they're decreasing and you find yourself weaker over time then you're not recovering well.
Homocysteine is an endogenous metabolite involved in methylation processes in the body. Mildly elevated homocysteine appears to be an independent risk factor for both cardiovascular[302] and atherosclerotic disease,[303] where if the 8-10μM normal range is elevated by around 5μM, it is thought to confer 60-80% greater risk of atherosclerotic disease[303]. Although it may not independently cause problems,[304] it may play a causative role in the context of the whole body system, since it is atherogenic by augmenting LDL oxidation[305] and promoting conversion of macrophages into foam cells.[306]

JAK2 (Janus-Activating Kinase 2) is a novel protein that has been shown to suppress the activity of the creatine transporter CrT in vitro. The effects of JAK2 on CrT are not well-understood in vivo, however. Given that growth hormone activates both c-src (increases CrT activity) and JAK2- which has been found to decrease CrT activity, it is plausible that JAK2 may function as a negative-feedback regulator of creatine uptake. Future research is needed to better understand the role of JAK2 on CrT activity in vivo.
More specifically, you can expect to end up in the upper half of these ranges ONLY if you are a beginner, younger, and/or have amazing genetics. You can expect to end up in the lower half of these ranges if you are an intermediate or advanced trainee, older, and/or have poor genetics. The average person can expect to end up somewhere in the middle. Additional details here: How Much Muscle Can You Gain?
A typical creatine supplementation protocol of either a loading phase of 20 to 25 g CM/d or 0.3 g CM/kg/d split into 4 to 5 daily intakes of 5 g each have been recommended to quickly saturate creatine stores in the skeletal muscle. However a more moderate protocol where several smaller doses of creatine are ingested along the day (20 intakes of 1 g every 30 min) could be a better approach to get a maximal saturation of the intramuscular creatine store. In order to keep the maximal saturation of body creatine, the loading phase must be followed by a maintenance period of 3-5 g CM/d or 0.03 g CM/kg/d. These strategies appear to be the most efficient way of saturating the muscles and benefitting from CM supplementation. However more recent research has shown CM supplementation at doses of 0.1 g/kg body weight combined with resistance training improves training adaptations at a cellular and sub-cellular level. Creatine retention by the body from supplementation appears to be promoted by about 25% from the simultaneous ingestion of carbohydrate and/or protein mediated through an increase in insulin secretion. This combination would produce a faster saturation rate but has not been shown to have a greater effect on 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.
A major benefit of the creatine pills is that they are much more convenient than the powder, so you can just throw a few in your bag without worrying about the mess of a powder spill or having to carry the entire tub around. Reviewers confirm that they’ve seen serious strength and muscle size gains since starting to take this supplement, even after just two weeks of use. One bottle of this creatine includes 90 capsules so you will be set for months of lifting sessions.
A: No. You should ensure that the squat and hinge motor pattern are both emphasized but other variations (front squat, sumo deadlift, safety bar squat, Romanian deadlift) should be included until you can master technique on the more advanced variations. For more information on exercise progressions and regressions see this article: Train Like An Athlete, Look Like a Bodybuilder.

The major controversies regarding creatine are its side effects and the best form to use. Nearly all side effects attributed to creatine, such as muscle cramps, kidney disease and gastrointestinal disturbances, haven't proved significant under controlled scientific scrutiny. Although various claims are made for a variety of creatine supplements, creatine monohydrate, which is 99 percent absorbed, is the best form to use.


Safety. Iron overload may cause a disease called hemochromatosis in some susceptible people. Iron supplements should only be prescribed by a doctor, and for athletes or those who train heavily, a sports physician combined with a sports dietitian may be preferable. Be sure to take care with this because iron supplements should not be taken casually. Iron supplements may cause constipation and gastric upset in some people.
“Compared to training for strength, intensity is going to drop during the hypertrophy phase of a program, with intensity sitting between 50 and 75 percent of the person’s 1RM, the maximum weight he or she can lift for one rep,” says Ava Fitzgerald, C.S.C.S., C.P.T., a sports performance coach with the Professional Athletic Performance Center in New York.
A quantitative, comprehensive scientific summary and view of knowledge up to 2007 on the effects of creatine supplementation in athletes and active people was published in a 100 citation review position paper by the International Society of Sports Nutrition[5]. More recent literature has provided greater insight into the anabolic/performance enhancing mechanisms of creatine supplementation [15,25] suggesting that these effects may be due to satellite cell proliferation, myogenic transcription factors and insulin-like growth factor-1 signalling [16]. Saremi et al [26] reported a change in myogenic transcription factors when creatine supplementation and resistance training are combined in young healthy males. It was found that serum levels of myostatin, a muscle growth inhibitor, were decreased in the creatine group.
Creatine is a hydrophilic polar molecule that consists of a negatively charged carboxyl group and a positively charged functional group [64]. The hydrophilic nature of creatine limits its bioavailability [65]. In an attempt to increase creatines bioavailability creatine has been esterified to reduce the hydrophilicity; this product is known as creatine ethyl ester. Manufacturers of creatine ethyl ester promote their product as being able to by-pass the creatine transporter due to improved sarcolemmal permeability toward creatine [65]. Spillane et al [65] analyzed the effects of a 5 days loading protocol (0.30 g/kg lean mass) followed by a 42 days maintenance phase (0.075 g/kg lean mass) of CM or ethyl ester both combined with a resistance training program in 30 novice males with no previous resistance training experience. The results of this study [65] showed that ethyl ester was not as effective as CM to enhance serum and muscle creatine stores. Furthermore creatine ethyl ester offered no additional benefit for improving body composition, muscle mass, strength, and power. This research did not support the claims of the creatine ethyl ester manufacturers.
When you’re doing higher reps, focus on the muscle you are trying to build and squeeze every ounce of effort out of it. Yes, cheesie as it may sound, visualizing the muscles working and growing while you train them can be helpful. A 2016 study in the European Journal of Applied Physiology found that, when lifters thought about their pecs and triceps during a workout, they activated them better.
If you’re not lifting super-heavy weights, doing high-intensity workouts, or eating a mainly vegan or vegetarian diet, your body probably makes as much creatine as it needs. “Creatine is naturally found in animal-based products,” says Bates, “so your body can make plenty of creatine as long as you have a balanced diet that includes animal-based products.” Protein sources like beef, chicken, pork, and fish help your body produce the creatine it needs — it varies depending on the source, but, in general, a 3-ounce serving of meat will have about 0.4 grams (g) of creatine, Bates says. (6)

Creatine monohydrate is highly regarded as one of the most powerful and all-around best bodybuilding supplements for athletes hoping to make big gains fast. Creatine is one of the go-to supplements for building mass because it maximizes power output, strength, endurance, and overall performance, helping you to crush your fitness goals time and time again.

Studies with animal and cellular models demonstrated positive effect of creatine ingestion on neurodegenerative diseases. These effects have been attributed to improved overall cellular bioenergetics due to an expansion of the phosphocreatine pool [50]. Creatine deficiency syndromes, due to deficiency of glycine amidinotransferase and guanidinoacetate methyltransferase, can cause decreases or complete absence of creatine in the central nervous system. Syndromes of this nature have the possibility to be improved by supplementing orally with creatine. Brain creatine deficiency resulting from ineffective crea T1 has been shown not to be effectively treated with oral creatine supplementation [51]. Additionally, oral creatine administration in patients with myopathies has shown conflicting results depending on the type of myopathy and creatine transport systems disorders [4].
Who makes it: Creapure HMB is made by Transparent Labs, one of the best companies in the sports nutrition industry. Transparent labs is all about, well, transparency! They always clearly list everything that goes into their products. They use pure, simple, and clinically proven ingredients to create products that get real results. Instead of relying on marketing gimmicks to sell their products, Transparent Labs relies on proven science and word-of-mouth. Transparent Labs has grown their business by providing the one ingredient seldom found in sports nutrition products: honesty.
It is known that intracellular energy depletion (assessed by a depletion of ATP) stimulates AMPK activity in order to normalize the AMP:ATP ratio,[333][334] and when activated AMPK (active in states of low cellular energy[335] and colocalizes with creatine kinase in muscle tissue[336]) appears to inhibit creatine kinase via phosphorylation (preserving phosphocreatine stores but attenuating the rate that creatine buffers ATP). While phosphocreatine technically inhibits AMPK, this does not occur in the presence of creatine at a 2:1 ratio.[334] It seems that if the ratio of phosphocreatine:creatine increases (indicative of excess cellular energy status) that AMPK activity is then attenuated, since when a cell is in a high energy status, there is less AMP to directly activate AMPK.[334][336][337]
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