The major controversies regarding creatine are its side effects and the best form to use. Nearly all side effects attributed to creatine, such as muscle cramps, kidney disease and gastrointestinal disturbances, haven't proved significant under controlled scientific scrutiny. Although various claims are made for a variety of creatine supplements, creatine monohydrate, which is 99 percent absorbed, is the best form to use.
Change things up. After six or more weeks of consistent strength training, which is about the amount of time it takes to start seeing improvement in your body, you can change your routine to make it more difficult. Lifting the same weights for the same exercises every week will keep your body in the same place. You can modify weights or repetitions, choose different exercises, or change the order in which you do them. You only have to make one change at a time to make a difference, although more is often better.
Creatine non-response is when muscular loading of creatine is under a certain threshold (10mmol/L), while “response” to creatine means having more muscular creatine loading (20mol/L or more). There also exists a “grey area” inbetween, where some benefits are achieved but not as many as pure responders will experience. Response appears to be positively correlated with muscle mass and type II muscle fibers.
In otherwise healthy adults subject to leg immobilization for two weeks while taking 20g creatine daily during immobilization and then 5g daily during eight weeks of rehabilitation, it was noted that the creatine group failed to reduce atrophy during the immobilization (10% reduction in cross sectional area and 22-25% reduction in force output) despite preventing a decrease in phosphocreatine, yet experienced a significantly enhanced rate of regrowth and power recovery. A similarly structured and dosed study has also noted greater expression of skeletal muscle, GLUT4 expression, and a 12% increase in muscle phosphocreatine content.
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.
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.
This claim has not been demonstrated at this time, and a recent comparative study of buffered creatine against basic creatine monohydrate found no significant differences between the two in 36 resistance trained individuals, in regard to the effects or the accumulation of creatine in muscle tissue. There also were no significant differences in the amount of adverse side-effects reported.
One study lasting 16 months using 10g creatine daily alongside the pharmaceutical riluzole noted that, after 34 of the patients died from ALS, creatine failed to exert protective effects against ALS-related mortality (adjusted hazard ratio of 0.78 with a 95% CI of 0.47–1.48). A smaller study measuring only eight deaths noted that the six in placebo (relative to two in creatine) was too small of a sample size to detect a statistically significant difference. A nonsignificant trend to increase survival has been noted elsewhere with 5g of creatine daily with a similar ratio: 3 deaths in placebo to 1 death in creatine.
Escolar, D. M., Buyse, G., Henricson, E., Leshner, R., Florence, J., Mayhew, J., Tesi-Rocha, C., Gorni, K., Pasquali, L., Patel, K. M., McCarter, R., Huang, J., Mayhew, T., Bertorini, T., Carlo, J., Connolly, A. M., Clemens, P. R., Goemans, N., Iannaccone, S. T., Igarashi, M., Nevo, Y., Pestronk, A., Subramony, S. H., Vedanarayanan, V. V., and Wessel, H. CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular dystrophy. Ann Neurol 2005;58:151-155. View abstract.
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. 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) 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.
I’m going to cover this in detail in a bit, but for right now, just know this: it’s VERY possible (and common) to gain weight fast in the hopes of gaining muscle fast. The problem, however, is that the majority of the “weight” a person in this scenario will end up gaining will be body fat rather than muscle mass. This is something that needs to be avoided at all costs, and I’ll show you how a little later.
These supplements can vary considerably from product to product in ingredients, serving sizes, and more. But the goal of each of them is generally quite similar. Most bodybuilding supplements are designed to help stimulate new muscle growth, cut away excess fat, and improve the recovery process so that you can get the most out of each trip to the gym.
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In your body, you can only store enough ATP for about 10 seconds of maximum exercise, this means that after those storages are depleted, it is up to your body to produce ATP to reach the demand your body is placing.  Creatine helps in the body by increasing stores of phosphocreatine which is the main ingredient used to create new ATP during intense exercise. By just supplementing creatine for 6 days, you can double your levels of creatine in your muscle storages, resulting in a higher capacity to create energy. 
In regard to bioenergetics, phosphorylated cyclocreatine appears to have less affinity for the creatine kinase enzyme than phosphorylated creatine in terms of donating the high energy phosphate group (about 160-fold less affinity) despite the process of receiving phosphorylation being similar. When fed to chickens, phosphorylated cyclocreatine can accumulate up to 60mM in skeletal muscle, which suggests a sequestering of phosphate groups before equilibrium is reached. Cyclocreatine still has the capacity to donate phosphate, however, as beta-adrenergic stimulated skeletal muscle (which depletes ATP and glycogen) exhibits an attenuation of glycogen depletion (indicative of preservation of ATP) with phosphocreatine.
I HATE that the resistance training community can be so tribal. I have been preaching to bodybuilders for years about the benefits of powerlifting, or Olympic lifting or kettlebells or even Crossfit style conditioning and many have been receptive. Learn from each other and achieve levels of fitness you simply could not have otherwise. Don’t brush off bodybuilding wisdom…it could be the missing factor in your program.
McArdle’s disease is a myopathy associated with impaired glucose release from glycogen and impairments in muscle function at times when glucose would be the primary energy substrate. Creatine is thought to be therapeutic, but has shown differing effects in the two trials so far (both benefit and worsening of symptoms) for currently unknown reasons.
One of the biggest goals of bodybuilders is to increase their muscle size and strength. Bodybuilding supplements often contain many ingredients that help to encourage this. Branched-chain amino acids are a common ingredient that can significantly increase muscle growth. Other ingredients help to increase the levels of hormones, such as growth hormone and testosterone, that can also stimulate muscle growth.
When splitting a sample into exercisers and non-exercisers, it appears that exercise as a pre-requisite precedes a higher range of activity. Inactive people tend to be on the lower end of creatine kinase activity and relatively clustered in magnitude, while exercise generally increases activity, but also introduces a larger range of possible activity.
In people whose kidneys don’t function optimally, supplemental creatine seems to be safe, too. However, studies in people with suboptimal kidney function are fewer than in healthy people, and they are short-term. People with kidney dysfunction, or at risk for developing kidney dysfunction (e.g., people with diabetes, high blood pressure, or family history of kidney disease; people over sixty; and non-Hispanic blacks), might wish to forgo creatine, or otherwise take only the lowest effective dose (3 g/day) after talking to their doctor.
When assessing the antioxidant effects of creatine, it does not appear to sequester superoxide and may not be a direct antioxidant. Additionally, creatine failed to protect neurons from H2O2 incubation to induce cell death via pro-oxidative means. These results are in contrast to previously recorded results suggesting creatine acts as a direct anti-oxidant.
AAKG β-hydroxy β-methylbutyrate Carnitine Chondroitin sulfate Cod liver oil Copper gluconate Creatine/Creatine supplements Dietary fiber Echinacea Elemental calcium Ephedra Fish oil Folic acid Ginseng Glucosamine Glutamine Grape seed extract Guarana Iron supplements Japanese Honeysuckle Krill oil Lingzhi Linseed oil Lipoic acid Milk thistle Melatonin Red yeast rice Royal jelly Saw palmetto Spirulina St John's wort Taurine Wheatgrass Wolfberry Yohimbine Zinc gluconate
Researchers found that 5g of creatine four times daily for a week (loading) before sleep deprivation for 12-36 hours was able to preserve cognition during complex tasks of executive function at 36 hours only, without significant influence on immediate recall or mood. A similar protocol replicated the failure to improve memory and attention, but noted less reports of fatigue (24 hours) and less decline of vigor (24 hours) although other mood parameters were not measured.
In regard to carbohydrate oxidation during exercise, it appears that rats subject to intermittent physical exercise (which utilizes glycogen) have decreased lactate production during said exercise, suggesting a preservation of glycogen usage. This occurred alongside an increase in glycogen stores. This is thought to be due to phosphocreatine donating phosphate to replenish ATP. Without any changes in whole body metabolic rate, it indirectly causes less glucose to be required to replenish ATP, due to a quota needing to be met during exercise and creatine phosphate taking up a relatively larger percentage of said quota.
That pump is tangible, real-time biofeedback to let you know that blood is flowing to your muscle cells, beginning a chain of events that stimulates protein synthesis. Maybe that's why it's easy to overlook how important good nutrition is in the mass-building equation. When you choose to eat, say, chicken instead of ice cream, there's no immediate muscle gratification -- no pump to keep you motivated.
Creatine is not an essential nutrient as it is naturally produced in the human body from the amino acids glycine and arginine, with an additional requirement for methionine to catalyze the transformation of guanidinoacetate to creatine. In the first step of the biosynthesis these two amino acids are combined by the enzyme arginine:glycine amidinotransferase (AGAT, EC:18.104.22.168) to form guanidinoacetate, which is then methylated by guanidinoacetate N-methyltransferase (GAMT, EC:22.214.171.124), using S-adenosyl methionine as the methyl donor. Creatine itself can be phosphorylated by creatine kinase to form phosphocreatine, which is used as an energy buffer in skeletal muscles and the brain.
How to maximize its effects: Take 20 grams of whey protein powder in the 30 minutes before working out, and take 40 grams within 60 minutes after training. Also consider taking 20-40 grams of whey immediately upon waking every morning to kick-start muscle growth. Your best bet is to choose a whey powder that contains whey protein hydrolysates (whey protein broken down into smaller fragments for faster digestion) or whey protein isolate.
The first published results (not blinded) noted that a loading phase of 20g of creatine for a week, followed by 3g daily for up to six months, was able to enhance maximal voluntary isometric muscular contraction (MVIC) on a dynamometer for both the knee and elbow joints, with enhanced fatigue resistance on the same joints in more than half of subjects (53-70% response rate).
Although weight training is similar to bodybuilding, they have different objectives. Bodybuilders use weight training to develop their muscles for size, shape, and symmetry regardless of any increase in strength for competition in bodybuilding contests; they train to maximize their muscular size and develop extremely low levels of body fat. In contrast, many weight trainers train to improve their strength and anaerobic endurance while not giving special attention to reducing body fat far below normal.
After all, you’ve probably seen the countless workouts, diets, supplements, programs, products and people claiming that super fast muscle growth is possible. You’ve probably also seen the click-bait headlines (“How To Build 20lbs Of Muscle In Just 6 Weeks!”) and the unbelievable transformations of supposedly “natural” people (bodybuilders, celebrities, athletes, fitness gurus on social media, etc.) that clearly prove it can happen faster than this.
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 . 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 . Sale et al  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.
In muscle cells, the creatine transporter is predominantly localized to the sarcolemmal membrane. Western blot analysis of creatine transporter expression revealed the presence of two distinc protein bands, migrating at 55kDa and 70kDa on reducing SDS-PAGE gels. The 73kDa band has been reported to be the predominant band in humans, with no differences based on gender. A more recent report demonstrated that the 55kDa creatine transporter variant is glycosylated, forming the 73 kDa protein. Therefore, the 55 and 75kDa protein bands are actually immature and mature/processed forms of the creatine transporter protein, respectively.