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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,[568] associated with reduced expression of the creatine transporter.[569] As creatine has once been noted to not accumulate in the skeletal muscle of people with DM1 given supplementation,[566] it is thought that the subjects did not respond to therapy.
Side-Effects: While the signs of a great body may make one think that there cannot be anything wrong with bodybuilding supplements, the facts speak otherwise. Bodybuilding supplements do have side-effects and you must listen to your trainer before giving in to the thoughts of buying one. Creatine can cause heart problems, kidney problems, dehydration, diarrhoea and muscle cramping. You must also discuss your medical history with the trainer. 
Gordon, P. H., Cheung, Y. K., Levin, B., Andrews, H., Doorish, C., Macarthur, R. B., Montes, J., Bednarz, K., Florence, J., Rowin, J., Boylan, K., Mozaffar, T., Tandan, R., Mitsumoto, H., Kelvin, E. A., Chapin, J., Bedlack, R., Rivner, M., McCluskey, L. F., Pestronk, A., Graves, M., Sorenson, E. J., Barohn, R. J., Belsh, J. M., Lou, J. S., Levine, T., Saperstein, D., Miller, R. G., and Scelsa, S. N. A novel, efficient, randomized selection trial comparing combinations of drug therapy for ALS. Amyotroph.Lateral.Scler. 2008;9(4):212-222. View abstract.

Do standard/oblique crunches. Lie down on a mat and position both arms behind your head without locking the hands. Bend your knees so that your feet are flat on the ground. Pushing the small of your back into the ground, slowly roll your shoulders off the ground only a couple of inches (not to a full sitting position). Don't use your momentum to help you up; use slow, regulated movements. Repeat 3 x 20.
Whey protein contains high levels of all the essential amino acids and branched-chain amino acids. It also has the highest content of the amino acid cysteine, which aids in the biosynthesis of glutathione. For bodybuilders, whey protein provides amino acids used to aid in muscle recovery.[27] Whey protein is derived from the process of making cheese from milk. There are three types of whey protein: whey concentrate, whey isolate, and whey hydrolysate. Whey concentrate is 29–89% protein by weight whereas whey isolate is 90%+ protein by weight. Whey hydrolysate is enzymatically predigested and therefore has the highest rate of digestion of all protein types.[27]
Despite a possible decreasing creatine content in the muscles when maintenance is deemed suboptimal, the overall retention of weight and lean mass is merely additive over time. This is thought to be due to increases in skeletal muscle production (increase in body weight) compensating for the progressive declines in water and glycogen content (decreases in body weight).
Creatine helps create essential adenosine triphosphate (ATP). This is the energy source of muscle contractions. By upping your levels, you can increase the amount of energy available to your muscles, boosting your performance. Because your muscle strength and size increases when you add weight and reps, improving your performance can be a game changer in terms of increasing your muscle mass. If you’re able to lift longer and harder, your muscles will grow. Creatine is certainly a winner among muscle building supplements.

That soreness you feel post-strength session may seem like a setback. Yet over time, you’ll come to acknowledge that it signifies you’re getting stronger. “You think, ‘I’ve done something worthwhile. My body is telling me I’ve had a workout.’ You look forward to the fatigue and interpret it in a positive way,” says John Spence, PhD, professor of physical education and recreation at the University of Alberta in Canada, who wrote a review on the effect of exercise on self-esteem. (Wondering how sore is too sore to work out? Here’s your answer.)
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]
In humans, studies that investigate links between serotonin and creatine supplementation find that 21 trained males, given creatine via 22.8g creatine monohydrate (20g creatine equivalent) with 35g glucose, relative to a placebo of 160g glucose, was found to reduce the perception of fatigue in hot endurance training, possibly secondary to serotonergic modulation, specifically attentuating the increase of serotonin seen with exercise (normally seen to hinder exercise capacity in the heat[233]) while possibly increasing dopaminergic activity (conversely seen to benefit activity in the heat[234]).[155]
Eat 1.5–3 grams of carbs per pound of your body weight. As with fat, this amount can vary greatly, depending on your personal needs and preferences, so consider these numbers only a starting point. If you’re very skinny and feel that you handle carbs well (i.e. you can eat a lot of them without getting fat), go ahead and eat according to the higher end of the spectrum. The same applies if you’re desperate to gain weight—you should increase your carb intake. If you’re prone to weight gain or feel lethargic on higher carbs, you should eat fewer of them. Again, see our keto guide for more details and options.

Español: aumentar la masa muscular, Deutsch: Muskeln aufbauen, Português: Aumentar a Musculatura, Nederlands: Spieren opbouwen, Français: se muscler le corps, Русский: нарастить мышечную массу, 中文: 增长肌肉, Čeština: Jak budovat svalovou hmotu, Bahasa Indonesia: Membangun Otot, Italiano: Sviluppare Massa Muscolare, 日本語: 筋肉をつける, हिन्दी: बॉडी बनायें (Kaise Body Banaye), العربية: بناء العضلات, 한국어: 근육을 키우는 법, Tiếng Việt: Tạo Cơ bắp, ไทย: สร้างกล้ามเนื้อ, Türkçe: Nasıl Kas Yapılır
Creatine has been incubated in various cell lines (HUVEC, C2C12, U937) and noted to reduce cellular death from various pro-oxidant stressors, such as H2O2 or peroxynitrate in an intracellular range between 0.1-10mM. This protective effect was only noted with preincubation and was comparable to 10-100µM of Trolox.[208] This protective effect did not require conversion into phosphocreatine nor a buffering of ATP, and only worked during a preloading to the stressor, rather than in a rehabilitative manner.[208]

The right amount of workout: It is highly possible that the protein powder you are taking doesn’t work on your body. Supplements should only be taken if you have a rigorous workout schedule or else, it will turn out to be of no value. Most people just purchase a box of supplements without really doing the math, which is very important. Unless you find out the dosage that suits you, the amount of time you should dedicate for the workout and so on, you must not expect daydream the results. 

I get lost every time I walk into my neighborhood GNC… the people who work there know their stuff, but nobody knows my body better than me and that’s where it all falls apart, but I’m working on that. I agree, I rather have grass-fed and more natural options as opposed to anything containing GMO in the products… The point is to become healthier, not go the other way…. But I also don’t want to get too much soy in my diet either… My wife is doesn’t want it for me and it’s given me headaches too, so I’m not really one for those. I guess small amounts of soy should be okay, right? Could someone be allergic to soy? There’s tons of other options though and I’m going to have to really look more into these here coz it has everything I’ve been looking for! Thanks for putting this together!


If you're a beginner, start with a basic total body strength workout to build a strong foundation in all your muscle groups. Taking this time will help you figure out any weaknesses you have, as well as any issues you may need to address with your doctor, and learn the basic exercises you need for a strong, fit body. Your first step is to figure out where you're going to exercise.
Athletic performance. Creatine seems to help improve rowing performance, jumping height, and soccer performance in athletes. But the effect of creatine on sprinting, cycling, or swimming performance varies. The mixed results may relate to the small sizes of the studies, the differences in creatine doses, and differences in test used to measure performance. Creatine does not seem to improve serving ability in tennis players.

A maintenance phase of 2g daily appears to technically preserve creatine content in skeletal muscle of responders either inherently or after a loading phase, but in sedentary people or those with light activity, creatine content still progressively declines (although it still higher than baseline levels after six weeks) and glycogen increases seem to normalize. This maintenance dose may be wholly insufficient for athletes, a 5g maintenance protocol may be more prudent.

Longer rest periods are more ideal for making progressive tension overload happen, and shorter rest periods are more ideal for generating metabolic fatigue. So, if you’re doing an exercise that is better suited for progressive overload (i.e. primary compound exercises), you’re going to want to rest longer between sets to maximize strength output. And if you’re doing an exercise that is better suited for metabolic fatigue (i.e. isolation exercises), you’re going to want to rest less between sets to make that happen. And if you’re doing an exercise that is suited equally for a combination of the two (i.e. secondary compound exercises), you’re usually going to want a moderate rest period somewhere in between.
How to Take It: So, you want to give it a go? How much should you take and what should you look for in a supplement? Definitely opt for creatine monohydrate, as it performs better in studies than other varieties, as mentioned above. A standard dose is about 5 grams a day. You can try taking this muscle builder for about 4 weeks to boost your levels. Following this time, you can either cut out creatine or lower to a maintenance dose of 3-5 grams per day. However, you’ll notice if you read the fine print that subjects in studies often have a loading phase of five days where the dosage is upped to 20 g per day, prior to adopting a standard dose (7, 8).
Several studies have used either beet root juice or pomegranate extract in multi-ingredient performance supplements and have observed improvements in strength, hypertrophy, and performance in resistance-trained men. At this point, however, it's difficult to determine if these benefits are from beet root juice and pomegranate extract working alone or synergistically with other ingredients.[11,12]
Due to the growing concerns of the high cost, health consequences, and illegal nature of some steroids, many organizations have formed in response and have deemed themselves "natural" bodybuilding competitions. In addition to the concerns noted, many promoters of bodybuilding have sought to shed the "freakish" perception that the general public has of bodybuilding and have successfully introduced a more mainstream audience to the sport of bodybuilding by including competitors whose physiques appear much more attainable and realistic.
In complex training, weight training is typically combined with plyometric exercises in an alternating sequence. Ideally, the weight lifting exercise and the plyometric exercise should move through similar ranges of movement i.e. a back squat at 85-95% 1RM followed by a vertical jump. An advantage of this form of training is that it allows the intense activation of the nervous system and increased muscle fibre recruitment from the weight lifting exercise to be utilized in the subsequent plyometric exercise; thereby improving the power with which it can be performed. Over a period of training, this may enhance the athlete's ability to apply power.[39] The plyometric exercise may be replaced with a sports specific action. The intention being to utilize the neural and muscular activation from the heavy lift in the sports specific action, in order to be able to perform it more powerfully. Over a period of training this may enhance the athlete's ability to perform that sports specific action more powerfully, without a precursory heavy lift being required.
Weight training also provides functional benefits. Stronger muscles improve posture, provide better support for joints, and reduce the risk of injury from everyday activities. Older people who take up weight training can prevent some of the loss of muscle tissue that normally accompanies aging—and even regain some functional strength—and by doing so, become less frail.[33] They may be able to avoid some types of physical disability. Weight-bearing exercise also helps to prevent osteoporosis.[34] The benefits of weight training for older people have been confirmed by studies of people who began engaging in it even in their eighties and nineties.
Your basal metabolic rate (BMR)—the calories you burn just to live—is driven by a host of factors, including your sex, genetics, and age, Tim Church, M.D., professor of preventative medicine at Pennington Biomedical Research Center at Louisiana State University, tells SELF. Research published in the medical journal PLOS ONE also shows that the size of your internal organs plays a huge role in why some people burn more calories at rest than others—in fact, the study found that 43 percent of the differences between people’s metabolic rates can be explained by organ size.

In a study on Alpha-Lipoic Acid, 1,000mg of ALA paired with 100g sucrose and 20g creatine monohydrate was more effective in increasing muscular creatine levels relative to creatine alone and creatine combined with sucrose.[600] This apparent augmentation of creatine uptake into muscle cells was used alongside a loading period. Another study investigating a nutrient mixture (150g glucose, 20g creatine, 2g/kg bodyweight glycerol) on heat tolerance in trained athletes found that replacing one third (50g) of the glucose with 1g ALA resulted in no significant differences between groups (in regard to heat tolerance and cardiovascular performance) despite the reduction of 50g carbohydrate.[601]
Creatine has been incubated in various cell lines (HUVEC, C2C12, U937) and noted to reduce cellular death from various pro-oxidant stressors, such as H2O2 or peroxynitrate in an intracellular range between 0.1-10mM. This protective effect was only noted with preincubation and was comparable to 10-100µM of Trolox.[208] This protective effect did not require conversion into phosphocreatine nor a buffering of ATP, and only worked during a preloading to the stressor, rather than in a rehabilitative manner.[208]
However, in the beginning weeks of starting a new workout routine, the majority of strength gains aren't actually a result of this muscle protein synthesis and hypertrophy. Rather, they are a result of the body's neurological system learning when and how to fire the needed muscle cells, explains Abbie E. Smith-Ryan, associate professor of exercise physiology at the department of exercise and sport science at the University of North Carolina–Chapel Hill. Think of it this way: The first time you perform a new exercise, say a bench press, you likely feel pretty shaky. Your arms aren't totally in sync and the weights may sway a bit from side to side. But by the time you perform your second or third set of that same exercise, the practice gets a little smoother. That's your neurological system at work.

While some supplements may in fact provide health benefits, generally speaking, consumers should purchase and use these products cautiously as they are not closely regulated by the Food and Drug Administration (FDA). Also, bodybuilders are advised to discuss supplementation plans with a registered dietitian or primary care physician prior to use to optimize effectiveness and minimize potential harmful consequences. 
Creatine, through its ability to act as an energy reserve, attenuates neuron death induced by the MPTP toxin that can produce Parkinson’s disease-like effects in research animals,[235] reduces glutamate-induced excitotoxicity,[236] attenuates rotenone-induced toxicity,[120] L-DOPA induced dyskinesia,[237] 3-nitropropinoic acid,[238] and preserves growth rate of neurons during exposure to corticosteroids (like cortisol), which can reduce neuron growth rates.[239] Interestingly, the energetic effect also applies to Alzheimer’s disease, during which creatine phosphate per se attenuates pathogenesis in vitro, yet creatine per se did not.[240]
What are the benefits of konjac? Konjac is a plant with a starchy root, or corm. This corm is used in dietary supplements and in the production of jellies and flour. Find out more about the potential health benefits of konjac, including managing diabetes, reducing cholesterol, and treating constipation. Get some tips, too, on how to use it safely. Read now
In addition to improving athletic performance and muscle strength, creatine is taken by mouth for creatine deficiency syndromes that affect the brain, aging, bone density, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), depression, diabetes, exercise tolerance, fibromyalgia, Huntington's disease, disease that cause inflammation in the muscles (idiopathic inflammatory myopathies), Parkinson's disease, diseases of the muscles and nerves, multiple sclerosis, muscle atrophy, muscle cramps, breathing problems in infants while sleeping, head trauma, Rett syndrome, an eye disease called gyrate atrophy, inherited disorders that affect the senses and movement, schizophrenia, muscle breakdown in the spine, and recovery from surgery. It is also taken by mouth to slow the worsening of amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), osteoarthritis, rheumatoid arthritis, McArdle's disease, and for various muscular dystrophies.
Although muscle stimulation occurs in the gym (or home gym) when lifting weights, muscle growth occurs afterward during rest periods. Without adequate rest and sleep (6 to 8 hours), muscles do not have an opportunity to recover and grow.[citation needed] Additionally, many athletes find that a daytime nap further increases their body's ability to recover from training and build muscles. Some bodybuilders add a massage at the end of each workout to their routine as a method of recovering.[50]
It’s important to remember that since everybody is different, these estimates are just that. How the numbers work out for each person will definitely vary. So many factors—like genetics, hormones, sleep, and diet—can change the rate at which our bodies burn calories. And some people may have a harder time than others when it comes losing fat or gaining muscle—again, there are so many factors at play and our body chemistries are all different. Strength training is important for many, many, many other reasons (more on that later), but if you’re looking to increase your metabolism, it’s important to have realistic expectations and know that strength training can make a difference, but probably won’t drastically affect how many calories you burn from one day to the next.
While the number of reps you do per set is important, of equal importance is the total number of reps you do per muscle group. The National Strength and Conditioning Association has determined that, to maximize growth, you need approximately 20–70 total reps per muscle group. Depending on which end of a rep range you’re working, this can be done in one session or over a few days (a training week, for instance), but that’s the spread you need to cover to see gains.
Pick a few key exercises that together train the whole body. Presses, chinups, rows, and squat and deadlift variations are the best choices (more on these in Rules #2 and #3). Write down how much weight you can currently do for 5–10 reps on each of them, and, over the next few months, work your way up to where you can either add 10–20 pounds to each of those lifts or do 3–5 more reps with the same weight. That’s how you force your body to grow.
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.

How to Take It: Take your gainer at any time of day as your objective is to reach overall calorie intake goals. Ideally, instead of using them as a meal substitute, you’ll use your gainer as a snack between high-calorie, healthy, balanced meals. If you plan on taking protein powder for muscle growth in addition to gainers, make sure you add up all of your dietary protein intakes to make sure it’s worth the investment of taking both. You might be able to skip the plain protein powders.


Try this little exercise some time: follow the supplement plan provided above for at least three months. Then quit all supplement use for a further three months and watch what happens. Sure, most supplement marketing involves hype and some companies make laughably outrageous claims, but there is no secret as to why the supplement industry is booming. Supplements work.
Creatine has been investigated for its effects on depression, due to the significant changes occurring in brain morphology and neuronal structure associated with depression[246] and low brain bioenergetic turnover in depression[247], perhaps related to abnormal mitochondrial functioning, which reduces available energy for the brain.[248][249] The general association of low or otherwise impaired phosphate energy systems (of which creatine forms the energetic basis of) with depression, has been noted previously.[250][247][251] Due to associations with cellular death and impaired bioenergetics with depression, creatine was subsequently investigated.
Squats target both your inner and outer thighs. Use a barbell heavy enough to challenge your muscles but light enough that you can still control your form. Hold it behind your head with your feet shoulder-width apart. Tighten your core, then squat down as far as comfortable. There should be no knee or back pain. As you come back up, raise your hips and chest together.

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.

Carducci, C., Birarelli, M., Leuzzi, V., Carducci, C., Battini, R., Cioni, G., and Antonozzi, I. Guanidinoacetate and creatine plus creatinine assessment in physiologic fluids: an effective diagnostic tool for the biochemical diagnosis of arginine:glycine amidinotransferase and guanidinoacetate methyltransferase deficiencies. Clin Chem 2002;48(10):1772-1778. View abstract. 

AAOS does not endorse any treatments, procedures, products, or physicians referenced herein. This information is provided as an educational service and is not intended to serve as medical advice. Anyone seeking specific orthopaedic advice or assistance should consult his or her orthopaedic surgeon, or locate one in your area through the AAOS Find an Orthopaedist program on this website.
"Start with two days for two to three weeks, then add a third day," says Davis*.*"Ideally, you should strength train three to five days per week, but work your way up—starting off at five days a week might shock your body." Here's a comprehensive three-day-per-week plan to get you started. Aim to complete 20-minute sessions, then gradually add on time in ten-minute increments until you're working for 45 to 60 minutes, suggests Davis. 

THIS TOOL DOES NOT PROVIDE MEDICAL ADVICE. It is intended for general informational purposes only and does not address individual circumstances. It is not a substitute for professional medical advice, diagnosis or treatment and should not be relied on to make decisions about your health. Never ignore professional medical advice in seeking treatment because of something you have read on the WebMD Site. If you think you may have a medical emergency, immediately call your doctor or dial 911.

The maximum amount of creatine the body can store is about 0.3 gram per kilogram of body weight [6]. The creatine content of skeletal (voluntary) muscles averages 125 millimoles per kilogram of dry matter (mmol/kg/dm) and ranges from about 60 to 160 mmol/kg/dm. Approximately 60% of muscle creatine is in the form of PCr. Human muscle seems to have an upper limit of creatine storage of 150 to 160 mmol/kg/dm. Athletes with high creatine stores don't appear to benefit from supplementation, whereas individuals with the lowest levels, such as vegetarians, have the most pronounced increases following supplementation. Without supplementation, the body can replenish muscle creatine at the rate of about 2 g/day [7].


Whether you’re taking a supplement or not, creatine is already functioning inside you, doing its very important job. It’s an amino acid found naturally in the meat and fish you consume and, according to the Mayo Clinic, your liver and kidneys crank it out as well. The creatine is mainly stored as creatine phosphate in your muscles, ready for use in energy production.
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].
Studies conducted in vegetarians tend to show cognitive enhancement in youth, possibly due to a creatine deficiency, as compared to omnivores.[272][60][61] Vegetarian diets have lower levels of circulating creatine prior to supplementation, but attain similar circulating levels as omnivores when both groups supplement.[272][273] Building on the latter, supplementation of creatine monohydrate in a loading protocol (20g daily in orange juice) in omnivores does not alter levels of creatine in white matter tissue in the brain (test subjects: competitive athletes).[274] In most of the parameters that vegetarians experience benefits, omnivores fail to experience statistically significant benefits[275], except possibly when sleep deprived, where the cognitive improvements rival that seen in vegetarians.[276] Elderly people who are omnivorous may also experience increases in cognition to a similar level, in regard to long-term memory as well as forward number and spatial recall, although the study in question failed to find any significant benefit on backward recall or random number generation,[38] the latter of which is a test for executive working memory.[277]

Tough workouts drive muscle growth, but they generally cause a lot of damage to your muscles to do so. This damage often results in soreness for several days, which can make it tough to get to the gym or sometimes even move. Many bodybuilding supplements contain ingredients that work to reduce the breakdown of muscle during workouts, making the recovery process easier on the body.
Bird, L. M., Tan, W. H., Bacino, C. A., Peters, S. U., Skinner, S. A., Anselm, I., Barbieri-Welge, R., Bauer-Carlin, A., Gentile, J. K., Glaze, D. G., Horowitz, L. T., Mohan, K. N., Nespeca, M. P., Sahoo, T., Sarco, D., Waisbren, S. E., and Beaudet, A. L. A therapeutic trial of pro-methylation dietary supplements in Angelman syndrome. Am J Med Genet.A 2011;155A:2956-2963. View abstract.
Creatine is known to occur in highly concetrated levels in chicken photoreceptors, relative to other parts of the eye (10-15mM[466]) alongside high levels of creatine kinase.[466] The creatine transporter in human eyes also seems to be concentrated in the photoreceptors,[468] which are known to be susceptible to hypoxic cellular death[471][472] which, for humans, usually means retinal detachment.[473]
Other areas of research include therapeutic uses of creatine to help patients with muscle wasting caused by disease states such as muscular dystrophy and amyotrophic lateral sclerosis (ALS). Small-scale preliminary studies show some gains in strength may be possible for these patients, which could improve their quality of life. One study of 81 patients with various neurologic diseases found that giving 10 g/day of creatine for five days, followed by 5 grams for another week, increases their muscle strength by about 10% [20]. Large-scale studies should be done before recommendations are made to such patients.
de Salles Painelli V, Alves VT, Ugrinowitsch C, et al. Creatine supplementation prevents acute strength loss induced by concurrent exercise. Eur J Appl Physiol 2014;114(8):1749-55.del Favero S, Roschel H, Artioli G, et al. Creatine but not betaine supplementation increases muscle phosphorylcreatine content and strength performance. Amino Acids 2012;42(6):2299-305. View abstract.
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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