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]
The motor proteins actin and myosin generate the forces exerted by contracting muscles. Current recommendations suggest that bodybuilders should consume 25–30% of protein per total calorie intake to further their goal of maintaining and improving their body composition.[30] This is a widely debated topic, with many arguing that 1 gram of protein per pound of body weight per day is ideal, some suggesting that less is sufficient, while others recommending 1.5, 2, or more.[31] It is believed that protein needs to be consumed frequently throughout the day, especially during/after a workout, and before sleep.[32] There is also some debate concerning the best type of protein to take. Chicken, turkey, beef, pork, fish, eggs and dairy foods are high in protein, as are some nuts, seeds, beans, and lentils. Casein or whey are often used to supplement the diet with additional protein. Whey protein is the type of protein contained in many popular brands of protein supplements and is preferred by many bodybuilders because of its high Biological Value (BV) and quick absorption rates. Whey protein also has a bigger effect than casein on insulin levels, triggering about double the amount of insulin release.[33] That effect is somewhat overcome by combining casein and whey. Bodybuilders are usually thought to require protein with a higher BV than that of soy, which is additionally avoided due to its claimed estrogenic properties. Still, some nutrition experts believe that soy, flax seeds and many other plants that contain the weak estrogen-like compounds or phytoestrogens, can be used beneficially, as phytoestrogens compete with estrogens for receptor sites in the male body and can block its actions. This can also include some inhibition of pituitary functions while stimulating the P450 system (the system that eliminates hormones, drugs and metabolic waste product from the body) in the liver to more actively process and excrete excess estrogen.[34][35] Cortisol decreases amino acid uptake by muscle, and inhibits protein synthesis.[36]
The creatine kinase (CK) enzyme in rat heart tissue appears to have a KM around 6mM of creatine as substrate.[280] and is known to positively influence mitochondrial function as higher cytoplasmic phosphocreatine concentrations (not so much creatine per se) increase the oxidative efficiency of mitochondria[280] This is thought to be due to the transfer of high energy phosphate groups.[280]
I was building up, bulking, going after the mass, which to me meant 230 pounds of sheer body weight. At that time, I didn’t care about my waist or anything else that would give me a symmetrical look. I just wanted to build a gigantic 250-pound body by handling a lot of weight and blasting my muscles. My mind was into looking huge, into being awesome and powerful. I saw it working. My muscles began bursting out all over. And I knew I was on my way.”
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.
Injections of creatine are known to be neuroprotective against low oxygen levels (hypoxia) even to neonatal rats.[532] This is thought to be associated with the increased collective pool of phosphocreatine and creatine.[236] Since oral ingestion of creatine by the mother increases brain concentrations of creatine by 3.6% in the fetus prior to birth,[531] it is thought to be protective in the fetuses subject to hypoxic (low oxygen) stressors, such as a caesarean section.
Creatine is normally metabolized into creatinine (note the difference in spelling), which is eliminated by the kidneys under normal conditions. When the kidneys fail and cannot clear the blood as effectively, many metabolites get “backlogged” in the blood. Creatinine is easy to measure and as such it is a biomarker of kidney damage.[623][624] If serum creatinine levels are elevated, the doctor may suspect some kidney damage. Low-dose creatine (≤5 g/day) may not cause alterations in this biomarker in otherwise normal adults[524][625][525] 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.[520][518][626][523][517] Most studies, however, have noted only a small increase in creatinine levels even with doses ≈20 g/day.[524][626][627]
Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.[26] Clinically, there are three distinct disorders of creatine metabolism. Deficiencies in the two synthesis enzymes can cause L-arginine:glycine amidinotransferase deficiency caused by variants in GATM and guanidinoacetate methyltransferase deficiency, caused by variants in GAMT. Both biosynthetic defects are inherited in an autosomal recessive manner. A third defect, creatine transporter defect, is caused by mutations in SLC6A8 and inherited in a X-linked manner. This condition is related to the transport of creatine into the brain.[27]

Another part of training isn't just doing the exercises, it's resting between the exercises. This comes with experience, but the general rule is, the higher the reps, the shorter the rest. So, if you're doing 15 reps, you might rest about 30 to 60 seconds between exercises. If you're lifting very heavy, say 4 to 6 reps, you may need up to two or more minutes.


Creatine, which is synthesized in the liver and kidneys, is transported through the blood and taken up by tissues with high energy demands, such as the brain and skeletal muscle, through an active transport system. The concentration of ATP in skeletal muscle is usually 2–5 mM, which would result in a muscle contraction of only a few seconds.[22] During times of increased energy demands, the phosphagen (or ATP/PCr) system rapidly resynthesizes ATP from ADP with the use of phosphocreatine (PCr) through a reversible reaction with the enzyme creatine kinase (CK). In skeletal muscle, PCr concentrations may reach 20–35 mM or more. Additionally, in most muscles, the ATP regeneration capacity of CK is very high and is therefore not a limiting factor. Although the cellular concentrations of ATP are small, changes are difficult to detect because ATP is continuously and efficiently replenished from the large pools of PCr and CK.[22] Creatine has the ability to increase muscle stores of PCr, potentially increasing the muscle’s ability to resynthesize ATP from ADP to meet increased energy demands.[23][24][25]
Consult your physician and follow all safety instructions before beginning any exercise program or using any supplement or meal replacement product, especially if you have any unique medical conditions or needs. The contents on our website are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment.
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]
No. It’s not easy for everyone to get the recommended amount of protein in their diets through good eating habits alone. Others may not have clinically low testosterone, but still benefit from boosting their levels to improve their muscle building capacity. You can fix these common problems through muscle building supplements. These easy to take pills and powders can also help you boost your performance at the gym which will, in turn, spur your body’s muscle building and recovery response.
Build an effective exercise routine. A good diet is required for your body to be able to maximize your potential, but there's no potential at all until you start the process of tearing down your old muscles and rebuilding them bigger, bulkier, and stronger. The best way to do that is to start at the beginning. If you're not sure where to begin, find a solid workout program online and try it out for a while. Don't immediately jump from one program to the next - you'll end up keeping yourself from making steady progress.
Syndromes caused by problems metabolizing creatine. Some people have a disorder that prevents their body from making creatine. This can lead to low levels of creatine in the brain. Low levels of creatine in the brain can lead to decreased mental function, seizures, autism, and movement problems. Taking creating by mouth daily for up to 3 years can increase creatine levels in the brain in children and young adults with a disorder of creatine production called guanidinoacetate methyltransferase (GAMT) deficiency. This can help improve movement and reduce seizures. But it doesn't improve mental ability. Arginine-glycine amidinotransferase (AGAT) deficiency is another disorder that prevents the body from making creatine. In children with this condition, taking creatine for up to 8 years seems to improve attention, language, and mental performance. But taking creatine does not seem to improve brain creatine levels, movement, or mental function in children who have a disorder in which creatine isn't transported properly.
It is possible that females could benefit more than males due to a combined lower creatine kinase activity as well as having altered purine metabolism during depression,[257] but no human comparative studies have been conducted yet. One rat study noted that creatine monohydrate at 2-4% of feed had 4% creatine able to exert anti-depressive and anxiolytic effects in female rats only.[228]
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: 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. 
If you decide to join a gym, know that you're not expected to know how all of the equipment works right off the bat—or what to do with it. Be sure to take advantage of the free orientation so you can learn how to properly use everything that's offered and set up a basic strength-training program. At the gym, machines are preferred for beginners, because they're quite safe: Most require little coordination and offer more stability than free weights while performing the movements. 
Glycogen synthesis is known to respond directly and positively to cellular swelling. This was demonstrated in an earlier study, during which rat muscle cells were exposed to a hypotonic solution in vitro to induce cell swelling, which increased glycogen synthesis by 75%. In contrast, exposing these same cells to a hypertonic solution hindered glycogen synthesis by 31%. These changes were not due to alterations in glucose uptake, but are blocked by hindering the PI3K/mTOR signaling pathway.[112] It was later noted that stress proteins of the MAPK class (p38 and JNK) as well as heat shock protein 27 (Hsp27) are activated in response to increasing osmolarity.[113][114] Furthermore, activation of MAPK signaling in skeletal muscle cells is known to induce myocyte differentiation[115] via GSK3β and MEF2 signaling, which can induce muscle cell growth.[116][117]
Contrary to the sound of the name, glucosamine is not a glucose replacement drink but a naturally occurring compound that has received publicity and wide support as a supplement for the relief of arthritis pain and possible prevention of further joint damage. Glucosamine has been popular with sports people of all types, including weight trainers, particularly for knee arthritis and pain. Glucosamine seems to be safe to use.
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]

Creatine citrate is creatine bound to citric acid, or citrate. Creatine citrate does not differ greatly from monohydrate in regard to absorption or kinetics.[83] Note that creatine citrate is more water-soluble than monohydrate,[84] but creatine absorption is generally not limited by solubility. The increased water solubility may play a factor in palatability.
Lyoo, I. K., Yoon, S., Kim, T. S., Hwang, J., Kim, J. E., Won, W., Bae, S., & Renshaw, P. F. (2012, September). A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder. American Journal of Psychiatry. 169(9):937-45. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22864465
It is possible that females could benefit more than males due to a combined lower creatine kinase activity as well as having altered purine metabolism during depression,[257] but no human comparative studies have been conducted yet. One rat study noted that creatine monohydrate at 2-4% of feed had 4% creatine able to exert anti-depressive and anxiolytic effects in female rats only.[228]
K. Aleisha Fetters, M.S., C.S.C.S., is a Chicago-based personal and online trainer. She has a graduate degree in health and science reporting from the Medill School of Journalism at Northwestern University and regularly contributes to Men's Health, Women's Health, USNews.com, TIME, and SHAPE. When she's not lifting something heavy, she's usually guzzling coffee and writing about the health benefits of doing so.
Yes, genetically some of us put on muscle faster than others, but even then it’s fractions of a degree, not DRASTIC sweeping differences. We tend to get this question from men or women who are so thin and have such fast metabolisms, they probably need to put on 40-50+ pounds of both fat and muscle, before they would ever even think to use the word “too bulky.”
Rheumatoid arthritis. Early research shows that taking creatine by mouth daily increases lean muscle mass and may improve muscle strength, but does not improve physical functioning in adults with rheumatoid arthritis. In children, taking a specific supplement containing creatine and fatty acids twice daily for 30 days might reduce pain and swelling. But the effects of creatine alone are not clear.

Anti-depressive effects have been noted in woman with major depressive disorder when 5g of creatine monohydrate was supplemented daily for 8 weeks in combination with an SSRI. Benefits were seen at week two and were maintained until the end of the 8-week trial.[253] The improvement in depressive symptoms was associated with significantly increased prefrontal cortex levels of N-acetylaspartate, a marker of neuronal integrity,[254] and rich club connections, which refers to the ability of nerons to make connections to one another.[255]

Escolar, D. M., Buyse, G., Henricson, E., Leshner, R., Florence, J., Mayhew, J., Tesi-Rocha, C., Gorni, K., Pasquali, L., Patel, K. M., McCarter, R., Huang, J., Mayhew, T., Bertorini, T., Carlo, J., Connolly, A. M., Clemens, P. R., Goemans, N., Iannaccone, S. T., Igarashi, M., Nevo, Y., Pestronk, A., Subramony, S. H., Vedanarayanan, V. V., and Wessel, H. CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular dystrophy. Ann Neurol 2005;58:151-155. View abstract.
Although creatine is a natural component of food, the amount of food required to supersaturate the muscle with PCr may not be feasible. For example, it could require 22 pounds of meat daily [8]. If creatine monohydrate is proven to be a safe and effective ergogenic aid, creatine supplementation may be the simplest way to increasing muscle stores. It may be beneficial to avoid caffeine if taking creatine supplements. One study showed that caffeine diminished strength gains seen with creatine use [9].
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