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]

The specific mechanism of intestinal uptake for creatine is not clear, although transporters have been identified in rat jujenum, and confirmed at the mRNA level in humans.[129][130] The observation that creatine can be absorbed against a concentration gradient to a max ratio of 8:1 (8 times more creatine in the intestinal cell post absorption, relative to the lumen) supports transporter-mediated uptake, and the dependence on sodium and chloride implicate SLC6A8 (Creatine Transporter 1) as the operative transporter.[102]
Knowledge – When it comes to building the best physique possible, you have to be willing to experiment and learn from your body. No one will be able to tell you what’s the most effective nutrition or training split for your individual genotype. Not only that, they don’t know your personal preference, injury history, asymmetries, experience level, or current work capacity.
Homocyteine (normal serum range of 5-14µM) is known to adversely affect motor control in genetically susceptible people when their levels exceed 500µM, which is usually associated with genetically induced deficiencies of B12.[360][361] In these particular instances (assessed by rats fed homocysteine to increase serum levels to such a high level[362][363]) it appears that administration of 50mg/kg creatine (injections) to these rats can protect dysfunction in muscle metabolism (pyruvate kinase activity, Krebs cycle intermediates, and muscle cell viability) induced by homocysteine.[363]
According to the abstract, in the stratified analyses by forms of aerobic exercise, weekly resistance exercise of 1 time or 1-59 minutes was associated with lower risks of total cardiovascular events and cardiovascular disease, regardless of meeting the aerobic exercise guidelines. The analysis showed that resistance training reduced the risk of cardiovascular events in 2 ways: training had a direct association with cardiovascular risk, and resistance training indirectly lowered cardiovascular risk by decreasing body mass index.
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.
The lower the rep range (and therefore the higher the intensity and the heavier the weight), the more rest there should be between sets. So most of the time, exercises being done in the 5-8 rep range need longer rest periods than exercises being done in the 8-10 rep range, which need longer rest periods than exercises being done in the 10-15 rep range.
A muscle imbalance—when one muscle is stronger than its opposing muscle—can limit your ability to exercise effectively, and could lead to injury down the line. “It’s important to recognize whether you’re really working the muscles you think you are and recognize if you’ve developed an imbalance that alters your movement pattern,” says Eric Ingram, physical therapist at Louisiana Physical Therapy Centers of Pineville. One common imbalance in women is stronger quads and weaker, tighter hamstrings, thanks to prolonged sitting, high heels, and improper training. If you suspect you have a muscle imbalance, make an appointment with a physical therapist, who will prescribe exercises to even you out.
One study on 27 otherwise healthy men supplementing creatine (0.3g/kg loading for a week, 0.05g/kg thereafter for 8 weeks) with a thrice weekly exercise regiment noted that alongside greater increase in lean mass and power relative to placebo at 4 and 8 weeks, myostatin in serum decreased to a greater extent with creatine (around 17% at 8 weeks, derived from graph) than it did with placebo (approximately 7%).[356] Increases in GASP-1, a serum protein that inhibits the actions of myostatin by directly binding to it,[357] were not different between groups.[356]
To combat steroid use and in the hopes of becoming a member of the IOC, the IFBB introduced doping tests for both steroids and other banned substances. Although doping tests occurred, the majority of professional bodybuilders still used anabolic steroids for competition. During the 1970s, the use of anabolic steroids was openly discussed, partly due to the fact they were legal.[9] In the Anabolic Steroid Control Act of 1990, U.S. Congress placed anabolic steroids into Schedule III of the Controlled Substances Act (CSA). In Canada, steroids are listed under Schedule IV of the Controlled Drugs and Substances Act, enacted by the federal Parliament in 1996.[10]
Lung disease (Chronic obstructive pulmonary disease). Early research on the effects of creatine in people with chronic obstructive pulmonary disease (COPD) is inconsistent. Some research suggests that taking creating daily does not improve lung function. However, other research suggests that taking creatine may improve lung function or exercise capacity.
It’s perhaps best known for the aesthetic benefits. Creatine increases muscle size relatively quickly and while that’s in part due to an increase in muscle water content — a good thing, since it means we’re better hydrated — it does indeed appear to lead to actual hypertrophy over time. And bigger muscles aren’t just aesthetic: larger muscles can improve work capacity, explosiveness, fat oxidation, injury resilience, and recovery.

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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.
A 2011 survey of 33 supplements commercially available in Italy found that over 50% of them exceeded the European Food Safety Authority recommendations in at least one contaminant. The most prevalent of these contaminants was creatinine, a breakdown product of creatine also produced by the body.[47] Creatinine was present in higher concentrations than the European Food Safety Authority recommendations in 44% of the samples. About 15% of the samples had detectable levels of dihydro-1,3,5-triazine or a high dicyandiamide concentration. Heavy metals contamination was not found to be a concern, with only minor levels of mercury being detectable. Two studies reviewed in 2007 found no impurities.[41]
Second, strength training has a much greater level of excess post-exercise oxygen consumption than aerobic exercise.  What does this mean?  When you finish a workout, your body needs to do a lot of work to replenish itself in order to bring itself back to a normal state (the way it was before you worked out).  This takes a lot of energy, and some studies have shown that it can boost your metabolism for up to 38 hours after you finish your workout.

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.
A dose of 5g daily has strong evidence supporting it not causing any adverse side effects[605] and 10g has been used daily for 310 days in older adults (aged 57+/-11.1) with no significant differences from placebo.[519] Such a dose has also been demonstrated for long-term safety for people with Parkinson’s disease,[606] and at least one small retrospective study in athletes (surverying people taking creatine for up to or over a year) failed to find any significant differences in a battery of serum health parameters.[502] Other studies measuring serum parameters have also failed to find abnormalities outside the normal range.[607]

As you've probably heard from any muscle-bound behemoth you've ever encountered, protein is the key to building muscle. Just because the shake-pounding meathead has become a trope, however, doesn't mean they're wrong; protein really is the fuel your muscles need to grow. That's real capital-S Science, not just bro-science manufactured by supplements companies.
The US FDA reports 50,000 health problems a year due to dietary supplements [14] and these often involve bodybuilding supplements.[15] For example, the "natural" best-seller Craze, 2012's "New Supplement of the Year" by bodybuilding.com, widely sold in stores such as Walmart and Amazon, was found to contain N,alpha-Diethylphenylethylamine, a methamphetamine analog.[16] Other products by Matt Cahill have contained dangerous substances causing blindness or liver damage, and experts say that Cahill is emblematic for the whole industry.[17]
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

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. 

Creatine is vital for brain function, which has mechanisms to take up creatine, as well as regulate its intake. Although the diet appears to be the major source of creatine (and thus lack of dietary intake could cause a non-clinical deficiency) excess levels of creatine do not appear to “super-load” the brain similar to muscle tissue. Due to kinetics, creatine appears to be more “preventative” or acts to restore a deficiency in the brain. This is in contrast to creatine effects in muscle cells, where it can affect performance substantially on an acute timescale.
Increasing creatine levels in skeletal muscle to 687% of baseline (0.5mM creatine, thought to be equivalent to 5g creatine[135]) doesn’t seem to per se increase glucose uptake, but increases glucose oxidation (140% of baseline)[341] which is due to a two-fold increase in the activity of α1 and α2 subunits of AMPK, a potency comparable to 1mM of the reference drug AICAR.[341] Glucose uptake associated with AMPK has indeed been noted in diabetic people who are undergoing physical exercise[342] and in contracting skeletal muscle cells,[153][330] but according to rat[343][344][345] and in vitro studies of cells not being contracted,[341] this is not a per se effect of non-exercising tissue but an augmentation of exercise-induced glucose uptake.
That said, many people experience stomach cramps when they consume creatine monohydrate and it’s possible that taking a creatine with a different pH — usually creatine hydrochloride — can have a different effect on stomach acid and make for a creatine that digests more easily. As far as we know, the easier digestion doesn’t necessarily mean it’s more effective or that you need less of it to achieve the desired result.
^ Jump up to: a b Barcelos RP, Stefanello ST, Mauriz JL, Gonzalez-Gallego J, Soares FA (2016). "Creatine and the Liver: Metabolism and Possible Interactions". Mini Reviews in Medicinal Chemistry. 16 (1): 12–8. doi:10.2174/1389557515666150722102613. PMID 26202197. The process of creatine synthesis occurs in two steps, catalyzed by L-arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT), which take place mainly in kidney and liver, respectively. This molecule plays an important energy/pH buffer function in tissues, and to guarantee the maintenance of its total body pool, the lost creatine must be replaced from diet or de novo synthesis.
Whey, the liquid remaining after milk has been curdled and strained, is rapidly digested and absorbed and has a remarkable ability to stimulate muscle protein synthesis (Hayes & Cribb, 2008). Whey is available in three varieties — whey protein powder, whey protein concentrate, whey protein isolate — and all provide high levels of the essential and branched chain amino acids, vitamins and minerals.

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.
^ Kreider RB, Kalman DS, Antonio J, Ziegenfuss TN, Wildman R, Collins R, Candow DG, Kleiner SM, Almada AL, Lopez HL (2017-06-13). "International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine". Journal of the International Society of Sports Nutrition. 14: 18. doi:10.1186/s12970-017-0173-z. PMC 5469049. PMID 28615996.
Over time, we naturally lose muscle mass in a process called sarcopenia. On average, men lose about 30% of their muscle mass during their lives. Usually, this begins in your 30s and progresses slowly as you age. But, don’t despair. You can rebuild and maintain muscle mass even as you age. Often, diet and exercise are enough. But, sometimes, if the above hormones play a role, your doctor may recommend medications and additional treatments (4).

The specific mechanism of intestinal uptake for creatine is not clear, although transporters have been identified in rat jujenum, and confirmed at the mRNA level in humans.[129][130] The observation that creatine can be absorbed against a concentration gradient to a max ratio of 8:1 (8 times more creatine in the intestinal cell post absorption, relative to the lumen) supports transporter-mediated uptake, and the dependence on sodium and chloride implicate SLC6A8 (Creatine Transporter 1) as the operative transporter.[102]
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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