Negative regulators of the creatine transporter (CrT) are those that, when activated, reduce the activity of the CrT and overall creatine uptake into cells. As noted above, CrT activity is positively regulated by mTOR.[158] Consistent with the well-known role of AMPK as a suppressor mTOR signaling,[177] CrT activity has also been shown to be inhibited in response to AMPK activation in kidney epithelial cells.[178] Since AMPK suppresses mTOR via upstream TSC2 activation,[179] the negative regulation of AMPK on CrT activity in these cells appears to occur through an indirect mechanism. Although indirect, activation of AMPK has been noted to reduce the Vmax of the CrT without altering creatine binding, and is involved in internalizing the receptors.[178] This pathway seems to max out at around 30% suppression, with no combination of mTOR antagonists and AMPK inducers further suppressing creatine uptake.[178]
There is a nuclear receptor known as TIS1 (orphan receptor, since there are no known endogeouns targets at this time) which positively influences transcription of new creatine transporters[171] and, in C2C12 myotubes, seems to be responsive to cAMP or adenyl cyclase stimulation from forskolin (from Coleus Forskohlii) with peak activation at 20µM.[171][172] 

Sure, using a more effective workout routine or diet plan will work better/faster than a less effective one. However, even when you’re doing everything just right and you’ve optimized every single major and minor factor to work as quickly and effectively as possible (which I’m going to show you how to do), the simple fact is that you’re still not going to build muscle “fast.”


Don’t take sets to the point of failure—where you absolutely can’t perform another rep. You should never get to where you’re turning purple and screaming like you’re getting interviewed by “Mean” Gene Okerlund before WrestleMania. Most of the time, you want to end your sets two reps before total failure. Not sure when that is? The moment your form breaks down, or you’re pretty sure it’s going to break down, end the set.
Post workout, it’s important to restore your body’s energy by consuming protein and carbs. When you’re trying to build muscle, this is an especially important step. Protein powder is a great muscle builder for your post-workout routine, as long as you include a carbohydrate as well. You can get this by eating a banana or adding oats or banana to your protein shake. Or simply cook up a batch of healthy oatmeal muffins and include protein powder in your recipe. Then, enjoy your post-workout supplement as a delicious snack!
A: Let your symptoms be your guide. A slight sore throat or runny nose may require you to back off for a day or two but don’t confine yourself to your bed and assume the worst. However, you must also remember that prolonged, intense exercise can decrease immune function and make you more susceptible to bacterial and viral based sickness so it's equally as important to listen to your body and respond accordingly.
It’s true—your genes can play a role when it comes to building muscle. In general, there are two types of muscle fibers: Type I, which are slow twitch, and Type II, which are fast twitch. Depending on which you have more of, you may have an easier or harder time gaining muscle. “Fast twitch muscle fibers are two times as thick as slow twitch muscle fibers, lending to the overall thickness of the muscle without any activity,” explains Lovitt. “Those people with a genetic predisposition of a high percentage of these fibers can increase muscle size very easily while the people with a higher percentage of slow twitch muscle fibers have to work really hard to put on mass.” It’s the reason why a world-class sprinter genetically has more fast twitch muscle fibers than a world-class marathoner—it comes down to what we’re born with.
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].
When it comes to finding the right meal plan, you have to start somewhere. Start with writing down what you eat in a food diary, calculate the calories you’re consuming daily (ex: 3,000 without protein shakes), and break those up into six meals (ex: 500 calories each), says Heath. Then, choose a macronutrient ratio. For example, the 40% protein, 40% carbs, 20% fat ratio is what Heath used to get bigger when he first started bodybuilding. “Buy a food scale, learn how to use it, and you may even have to learn to use the metric system, like grams instead of ounces,” Heath says. “You need to train your body to process food quickly, so eat every three hours.”
The synthesis of creatine (from guanidinoacetate via GAMT) also requires SAMe as a cofactor and is implicated in homocysteine production. While supplementation of guanidinoacetate at 0.36% (prior to SAMe) can increase homocysteine by up to 50% in rats, supplementation of creatine (0.4%) is able to suppress homocysteine by up to 25%, secondary to reducing creatine synthesis,[309] and has been replicated elsewhere with 2% of the rat diet, while a loading phase did not alter the benefits.[124]

COX-2, a pro-inflammatory enzyme, is sometimes a therapeutic target for both muscle soreness and some degenerative diseases that are exacerbated by inflammation. COX-2 inhibitors (in this study, rofecoxib) and creatine monohydrate both appear to protect dopaminergic neurons from being destroyed by toxins, and can protect in an additive manner, suggesting possible usage of both to reduce the risk of Parkinson’s disease.[230]


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.

When lifting any weight, you’ve got a concentric (hard) and eccentric (easy) phase. For instance, as you lower into a squat, you’re performing an eccentric action. When you return to standing, that’s concentric. And, according to research published in the European Journal of Applied Physiology, eccentric work is far better at triggering hypertrophy.
In the 1970s, bodybuilding had major publicity thanks to the appearance of Arnold Schwarzenegger, Franco Columbu, Lou Ferrigno, and others in the 1977 docudrama Pumping Iron. By this time, the IFBB dominated the competitive bodybuilding landscape and the Amateur Athletic Union (AAU) took a back seat. The National Physique Committee (NPC) was formed in 1981 by Jim Manion,[7] who had just stepped down as chairman of the AAU Physique Committee. The NPC has gone on to become the most successful bodybuilding organization in America and is the amateur division of the IFBB. The late 1980s and early 1990s saw the decline of AAU-sponsored bodybuilding contests. In 1999, the AAU voted to discontinue its bodybuilding events.
When it comes to finding the right meal plan, you have to start somewhere. Start with writing down what you eat in a food diary, calculate the calories you’re consuming daily (ex: 3,000 without protein shakes), and break those up into six meals (ex: 500 calories each), says Heath. Then, choose a macronutrient ratio. For example, the 40% protein, 40% carbs, 20% fat ratio is what Heath used to get bigger when he first started bodybuilding. “Buy a food scale, learn how to use it, and you may even have to learn to use the metric system, like grams instead of ounces,” Heath says. “You need to train your body to process food quickly, so eat every three hours.”

Our bodies store creatine in our muscles so that we have quick access to it for fast, high-intensity movements, like sprinting or powerlifting, explains Autumn Bates, a certified clinical nutritionist and sports nutritionist in private practice in Manhattan Beach, California. “It's a nonessential amino acid, meaning your body creates it and you don't need to primarily get it from food.”
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.
Forbes, S. C., Sletten, N., Durrer, C., Myette-Côté, E , Candow, D., & Little, J. P. (2017, June). Creatine monohydrate supplementation does not augment fitness, performance, or body composition adaptations in response to four weeks of high-intensity interval training in young females. Human Kinetics Journals, 27(3), 285-292. Retrieved from http://journals.humankinetics.com/doi/abs/10.1123/ijsnem.2016-0129

Even if you have a schedule that allows for a 5-day workout split, many people (I’d even call it the majority) simply don’t have the recovery capacity needed to make that work. This could be due to genetics, age, injury history, various lifestyle factors (sleep, stress, etc.) and more. In these cases, better results would be seen with 3-4 workouts per week instead.

However, caffeine does not negate the benefits of creatine loading when not coingested, but just taken before exercise in the same dosage.[593] This result indicates that loading creatine without caffeine on a daily basis, but saving caffeine for select workouts, may be an effective strategy, as creatine does not adversely affect caffeine’s ergogenic effects[593][594] and may enhance creatine’s effectiveness in anaerobic exertion if the two compounds are alternated.[595]
Creatine kinase is expressed in eyes. The eyes can take creatine up from the blood via two different transporters, the classic SCL6A8 (creatine transporter) and MCT12. It seems that expression of the receptors and accumulation of creatine occur in a relatively higher level in photoreceptors, which perceive color. Similarly to many other tissues, they appear to protect the cells during periods of low oxygen availability.

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.

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