Creatine has been noted to increase the amplitude (0.5-5mM) and frequency (25mM only) of NMDA receptors, although concentrations of 0.5-25mM also reduced signaling intensity. This was credited to creatine causing an increase in ligand binding of glutamate with an EC50 of 67µM and maximal activity at 1mM creatine (158±16% of baseline). Creatine appears to modulate the polyamine binding site of the NMDA receptor, as it is abolished by arcaine and potentiated by spermidine. This binding site is known to modify NMDA receptor affinity.
The creatine kinase system appears to be detectable in endothelial cells. Under basal conditions, creatine itself is expressed at around 2.85+/-0.62μM (three-fold higher than HUVEC cells). When incubating the medium with 0.5mM creatine, endothelial cells can take up creatine via the creatine transporter (SLC6A8) and increase both creatine (almost doubling) and phosphocreatine (nearly 2.5-fold) concentrations.
Creatine monohydrate is the most common form of creatine, and if not otherwise mentioned is the default form of creatine used in most studies on creatine. It has fairly decent intestinal absorption (covered more in depth in the pharmacology section) and is the standard form or “reference” form of creatine, which all other variants are pitted against.
Who makes it: This product is manufactured by MuscleTech, a large sports nutrition company that has been in business since 1995. In their 20+ years in the industry, MuscleTech has developed many innovative and effective exercise supplements, and currently holds more than 50 U.S. patents. They have developed quite a following of loyal fans over the years, and for good reason.
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.
When looking specifically at human studies, there has been a failure of creatine supplementation to induce or exacerbate kidney damage in people with amyotrophic lateral sclerosis (ALS). Subjects do not experience kidney damage for up to or over a year’s worth of supplementation in the 5-10g range. Postmenopausal women, people with type II diabetes, people on hemodialysis, otherwise healthy elderly, young people, and athletes do not experience kidney damage either. Moreover, numerous scientific reviews on both the long- and short-term safety of supplemental creatine have consistently found no adverse effects on kidney function in a wide range of doses. However, while doses >10 g/day have been found not to impair kidney function, there are fewer long-term trials using such high chronic daily intakes.
Creatine supplementation may be able to enhance lifespan, secondary to increasing intracellular carnosine stores. Carnosine is the metabolic compound formed from beta-alanine supplementation, and in a mouse-model for premature aging (senescence-accelerated premature aging, SAMP8) creatine supplementation without any beta-alanine has been shown to increase cellular carnosine stores. That being said, the aforemented SAMP8 study noted an increase in carnosine levels at middle age, but not old age in the mice. A human study using 20g of creatine for one week in otherwise healthy people failed to find an increase in intracellular carnosine stores.
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.
Polyethylene glycol is a non-toxic, water-soluble polymer that is capable of enhancing the absorption of creatine and various other substances . Polyethylene glycol can be bound with CM to form polyethylene glycosylated creatine. One study  found that 5 g/d for 28 days of polyethylene glycosylated creatine was capable of increasing 1RM bench press in 22 untrained young men but not for lower body strength or muscular power. Body weight also did not significantly change in the creatine group which may be of particular interest to athletes in weight categories that require upper body strength. Herda et al  analyzed the effects of 5 g of CM and two smaller doses of polyethylene glycosylated creatine (containing 1.25 g and 2.5 g of creatine) administered over 30 days on muscular strength, endurance, and power output in fifty-eight healthy men. CM produced a significantly greater improvement in mean power and body weight meanwhile both CM and polyethylene glycosylated form showed a significantly (p < 0.05) greater improvement for strength when compared with control group. These strength increases were similar even though the dose of creatine in the polyethylene glycosylated creatine groups was up to 75% less than that of CM. These results seem to indicate that the addition of polyethylene glycol could increase the absorption efficiency of creatine but further research is needed before a definitive recommendation can be reached.
Green tea offers many health benefits, such as inhibition of cardiovascular disease and cancer. It also has some mild thermogenic effects, independent of its caffeine content, that may assist fat loss. Some studies even show that green tea offers protection against joint degeneration. If you don't have the time or inclination to drink several cups of green tea daily, you can get the same or better effects by using standardized capsules or tablets of green tea.
Because I don’t want you to have to waste all the years and money that I did (not to mention the surgeon’s bills), I came up with a method of training and eating specifically for skinny-fat, injury-prone hard-gainers: guys who historically can’t gain muscle doing the workouts they find in magazines or on blogs. It’s also perfect for all guys over age 35 who need to be smarter with their training as they age.
Creatine supplementation appears to augment the anti-cancer effects of Vitamin C and methylglyoxal, a metabolic by-product of glycolysis. Methylglycoxal appears to inhibit step 1 of the electron transport chain in isolated mitochondria and cancerous mitochondria, but has not been implicated in doing so in normal tissue, as protective measures in normal cells appear to exist.
Research shows that strength training is especially effective at raising EPOC. That’s because, generally speaking, strength-training sessions cause more physiological stress to the body compared to cardiovascular exercise, even higher-intensity cardio intervals. However, it’s worth noting that overall exercise intensity is what makes the biggest impact on EPOC. So squats, deadlifts, and bench presses with heavy weights are going to be much more effective at raising EPOC compared to bicep curls and triceps extensions with light weights.