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]

There appears to be some potential for creatine supplementation. However, many questions remain. Are there any long-term harmful effects from supplementation? Is there a point where enhanced performance levels off from long-term supplement usage? What effect does "stacking" or taking two ergogenic aids simultaneously have on the body? What happens if you immediately stop taking the creatine supplement? Is the enhanced performance great enough to warrant the expense of the supplement? Until further research answers these questions, creatine is not recommended for the average athlete.
An isolation exercise is one where the movement is restricted to one joint only. For example, the leg extension is an isolation exercise for the quadriceps. Specialized types of equipment are used to ensure that other muscle groups are only minimally involved—they just help the individual maintain a stable posture—and movement occurs only around the knee joint. Most isolation exercises involve machines rather than dumbbells and barbells (free weights), though free weights can be used when combined with special positions and joint bracing.
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.”
Why it made the list: Whey tops the list of mass-gain supplements because it's the most crucial for pushing protein synthesis. Whey is a milk protein that has a high level of branched-chain amino acids (BCAAs, No. 4 on our list). Bottom line: Whey takes the crown because it digests fast and gets to your muscles rapidly to start building muscle. Whey also contains peptides (small proteins) that increase blood flow to the muscles. This is why we always recommend consuming whey protein immediately after training.
Creatine has been shown to influence androgen levels. Three weeks of creatine supplementation has been shown to increase dihydrotestosterone (DHT) levels, as well as the DHT:testosterone ratio with no effects on testosterone levels.[430] In contrast, creatine supplementation has been shown to increase testosterone levels when taken alongside a 10-week resistance training program.[431] A study in male amateur swimmers also noted that a creatine loading phase (20g daily for six days) was able to increase testosterone levels by around 15% relative to baseline.[397] 
Volek, J. S., Ratamess, N. A., Rubin, M. R., Gomez, A. L., French, D. N., McGuigan, M. M., Scheett, T. P., Sharman, M. J., Hakkinen, K., and Kraemer, W. J. The effects of creatine supplementation on muscular performance and body composition responses to short-term resistance training overreaching. Eur.J.Appl.Physiol 2004;91(5-6):628-637. View abstract.
Eat 0.4–0.5 grams of fat per pound of your body weight. Fat is essential for hormone optimization, brain function, and joint health. Now, if you’re following a ketogenic diet (or modified keto diet), or you just feel better with more fat in your diet, you can certainly add more fat and lower your protein and carb intake to accommodate it. The 0.4–0.5 grams per pound recommendation just represents a starting point and a minimum so that you don’t eat too little fat, either out of fear that it will make you fat or damage your heart (both untrue). For more about ketogenic diets, see Onnit’s guide HERE.
“Reg Park’s theory was that first you have to build the mass and then chisel it down to get the quality; you work on your body the way a sculptor would work on a piece of clay or wood or steel. You rough it out””the more carefully, the more thoroughly, the better”” then you start to cut and define. You work it down gradually until it’s ready to be rubbed and polished. And that’s when you really know about the foundation. Then all the faults of poor early training stand out as hopeless, almost irreparable flaws. [..]
Another double-blind study supplemented with 18.75 g/day of creatine monohydrate for 5 days prior to high-intensity intermittent work to exhaustion, and then 2.25 g/day during testing. The workouts consisted of cycling to exhaustion using several protocols: (a) nonstop, (b) 60 seconds work/120 seconds rest, (c) 20 seconds work/40 seconds rest, and (d) 10 seconds work/20 seconds rest. Creatine supplementation significantly increased the total work time for all four protocols [13].
The first thing you need is a weight training program that signals the muscle building process to begin. Research has shown that a well designed program will generate this “signal” via a combination of progressive tension overload (as in, getting stronger over time), metabolic stress (as in, fatiguing the muscle and getting “the pump”), and muscular damage (as in, actual damage to the muscle tissue itself).
Don’t get us wrong—cardio is important for keeping your body fat down and keeping your heart health in check. (Bonus points if you run or bike, since outdoor exercise is linked to better energy and improved mental health.) But when it comes to building muscle, hitting the treadmill won't help you much. “Every component of exercise, minus cardio, can help with muscle hypertrophy,” which is the scientific term for muscle building, says Michelle Lovitt, an exercise physiologist and trainer in Los Angeles. “Cardio tends to burn calories and puts your body in a deficit, which is great for leaning out, but not building mass.”
Minor liver lesions (grade I, no grade II or III, pathology not indicative of toxicity) have been studied in SOD1 G93A transgenic mice (a research model for amyotrophic lateral sclerosis or ALS, but used in this study to assess a state of chronic pro-oxidative stress) for 159 days with 2% of feed intake and in CD-1 rats (seen as normal) over 56 days with 0.025-0.5mg/kg in CD-1 mice, although in Sprague-Dawley rats (normal controls) there were no significant differences noted even after 2% of feed intake for 365 days.[503] These observations appear to be due to the strain of the rodents used,[504][503] and human studies on amyotrophic lateral sclerosis (ALS; what the SOD1 G93A transgenic mice are thought to represent) lasting from nine to sixteen months with subjects supplementing with up to 10g of creatine daily have failed to find any abnormalities in serum biomarkers of liver or kidney health.[505][506][507]
Even if your focus is on a particular body part, say getting flat abs or losing fat around the hips, it's important to work all your muscle groups. Spot reduction doesn't work, so doing crunches for your abs or leg lifts for your thighs isn't going to help you achieve your goal. What does work is building more lean muscle tissue and burning more calories.
Branched-chain amino acids (leucine, isoleucine, valine) play important roles in muscle building. Some researchers have found that following exercise, the branched-chain amino acids, especially leucine, increase the rate of protein synthesis and decrease the rate of protein catabolism (Blomstrand, 2006). The billion dollar supplement industry has been quick to respond; leucine supplements are widely available in health food stores, with a cost upwards of $50 per container. However, because the research findings are inconsistent and little is known about the safety of these products, the American Dietetic Association (soon to be renamed the Academy of Nutrition and Dietetics) advises against individual amino acid supplementation and protein supplementation overall (Rodriquez, 2009). It may be that food sources of these proteins and amino acids provide the same effect for a small fraction of the cost.
A typical creatine supplementation protocol consists of a loading phase of 20 g CM/d or 0.3 g CM/kg/d split into 4 daily intakes of 5 g each, followed by a maintenance phase of 3-5 g CM/d or 0.03 g CM/kg/d for the duration of the supplementation period [5]. Other supplementation protocols are also used such as a daily single dose of around 3 – 6 g or between 0.03 to 0.1 g/kg/d [15,55] however this method takes longer (between 21 to 28 days) to produce ergogenic effects [5]. Sale et al [56] found that a moderate protocol consisting of 20 g CM taken in 1g doses (evenly ingested at 30-min intervals) for 5 days resulted in reduced urinary creatine and methylamine excretion, leading to an estimated increase in whole body retention of creatine (+13%) when compared with a typical loading supplementation protocol of 4 x 5 g/d during 5 days (evenly ingested at 3 hour intervals). This enhancement in creatine retention would lead to a significantly higher weight gain when people follow a moderate protocol ingestion of several doses of small amounts of CM evenly spread along the day.

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.