Product reviews – Since the effectiveness of products varies based on a wide number of factors, one of the best things to do is read creatine product reviews. The best rated creatine products will have consistently good reviews, meaning a lot of people use that product and would recommend it. However – remember to take reviews with a grain of salt, as there’s a lot of ignorance and misinformation out there.
Creatine is involved indirectly in whole body methylation processes. This is due to creatine synthesis having a relatively large methyl cost, as the creatine precursor known as guanidinoacetate (GAA) requires a methyl donation from S-adenosyl methionine (SAMe) in order to produce creatine. This may require up to half of the methyl groups available in the human body.[35][122]
Because so many product labels list scientific references to back up the manufacturers' claims of performance and efficacy, or effectiveness, it's important to understand what constitutes a solid scientific study. A single study, even an optimally designed one, isn't considered scientific proof. The results have to be replicated several times before they're officially accepted as fact.
One case study exists of a man with focal segmental glomerulosclerosis who experienced an accelerated rate of GFR decline during supplementation (5g thrice daily for loading, then a 2g maintenance for seven weeks) which was partially reversed upon supplement cessation. This was deemed strong circumstantial evidence, and the brand of supplement was not named.[616] Elsewhere, interstitial nephritis associated with creatine supplementation has been reported in a man, although symptoms arose four weeks after supplementation started with no evidence to support correlation.[617] Some studies involving athletes and various dietary supplements have attempted to draw a correlation with creatine and cases of rhabdomyolysis.[618][619][620][621] Finally, one study in a diabetic person ingesting both metformin and creatine resulting in metabolic acidosis has attempted to place causation on creatine, but it did not establish causation or circumstantial evidence.[622]
Mercimek-Mahmutoglu, S., Stoeckler-Ipsiroglu, S., Adami, A., Appleton, R., Araujo, H. C., Duran, M., Ensenauer, R., Fernandez-Alvarez, E., Garcia, P., Grolik, C., Item, C. B., Leuzzi, V., Marquardt, I., Muhl, A., Saelke-Kellermann, R. A., Salomons, G. S., Schulze, A., Surtees, R., van der Knaap, M. S., Vasconcelos, R., Verhoeven, N. M., Vilarinho, L., Wilichowski, E., and Jakobs, C. GAMT deficiency: features, treatment, and outcome in an inborn error of creatine synthesis. Neurology 8-8-2006;67:480-484. View abstract.
Studies of so-called "smart drugs" have also been taken out of context. Some "smart" nutrients, available over the counter, are marketed as a way to "increase mental focus and concentration during training." The problem is that the studies they're based upon involved either animals or people with brain pathology. In normal people the effects of smart drugs remain unproven, except anecdotally.

de Salles Painelli V, Alves VT, Ugrinowitsch C, et al. Creatine supplementation prevents acute strength loss induced by concurrent exercise. Eur J Appl Physiol 2014;114:1749-55.del Favero S, Roschel H, Artioli G, et al. Creatine but not betaine supplementation increases muscle phosphorylcreatine content and strength performance. Amino Acids 2012;42:2299-305. View abstract.


Other areas of research include therapeutic uses of creatine to help patients with muscle wasting caused by disease states such as muscular dystrophy and amyotrophic lateral sclerosis (ALS). Small-scale preliminary studies show some gains in strength may be possible for these patients, which could improve their quality of life. One study of 81 patients with various neurologic diseases found that giving 10 g/day of creatine for five days, followed by 5 grams for another week, increases their muscle strength by about 10% [20]. Large-scale studies should be done before recommendations are made to such patients.
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.[358] A similarly structured and dosed study has also noted greater expression of skeletal muscle, GLUT4 expression, and a 12% increase in muscle phosphocreatine content.[330]
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]

Chwalbinska-Monteta [34] observed a significant decrease in blood lactate accumulation when exercising at lower intensities as well as an increase in lactate threshold in elite male endurance rowers after consuming a short loading (5 days 20 g/d) CM protocol. However, the effects of creatine supplementation on endurance performance have been questioned by some studies. Graef et al [35] examined the effects of four weeks of creatine citrate supplementation and high-intensity interval training on cardio respiratory fitness. A greater increase of the ventilatory threshold was observed in the creatine group respect to placebo; however, oxygen consumption showed no significant differences between the groups. The total work presented no interaction and no main effect for time for any of the groups. Thompson et al [36] reported no effects of a 6 week 2 g CM/d in aerobic and anaerobic endurance performance in female swimmers. In addition, of the concern related to the dosage used in these studies, it could be possible that the potential benefits of creatine supplementation on endurance performance were more related to effects of anaerobic threshold localization.
In weight training, as with most forms of exercise, there is a tendency for the breathing pattern to deepen. This helps to meet increased oxygen requirements. Holding the breath or breathing shallowly is avoided because it may lead to a lack of oxygen, passing out, or an excessive build up of blood pressure. Generally, the recommended breathing technique is to inhale when lowering the weight (the eccentric portion) and exhale when lifting the weight (the concentric portion). However, the reverse, inhaling when lifting and exhaling when lowering, may also be recommended. Some researchers state that there is little difference between the two techniques in terms of their influence on heart rate and blood pressure.[8] It may also be recommended that a weight lifter simply breathes in a manner which feels appropriate.
You've got your equipment ready, now it's time to choose about eight to 10 exercises, which comes out to about one exercise per muscle group. Use the list below to choose at least one exercise per muscle group to start. For the larger muscles, like the chest, back, and legs, you can usually do more than one exercise. These involve a variety of equipment, so you can choose based on what you have available. 

SAMe is the primary methyl donor in the human body, and supplements that preserve SAMe (such as trimethylglycine; TMG) promote a variety of benefits in the human body, like a reduction in homocysteine and reduced risk of fatty liver. Creatine has been implicated in both reducing homocysteine[124] and preventing fatty liver in rodents[125], thought to be secondary to preserving SAMe.
Naturo Nitro Creatine Chrome is an interesting choice for bulking. During the bulking process, many athletes lament losing muscle definition and feeling bloated. The magnesium creatine chelate in Naturo Nitro may help to counteract that effect as there’s some evidence that it could potentially improve performance without adding water weight. If you want to bulk but you want to keep definition, this may be worth considering.
Competitive and professional bodybuilders, however, can often build up to two to three pounds of muscle per month during dedicated bulking periods. "But they are living and breathing muscle growth. They aren't just in and out of the gym like most people," Simpson says, noting that under extreme conditions, hyperplasia, or the growth in the number of muscle cells in a given muscle tissue, may actually occur, further adding to muscle growth results.

There is a great amount of research published on creatine supplementation; protocols of administration, forms of creatine, as well as potential side effects. Despite this, the mechanisms by which creatine acts in the human body to improve physical and cognitive performance are still not clear. The main objectives of this review are to analyze the more recent findings on the effects and mechanisms of creatine supplementation in sports and health. As a secondary purpose, we will analyze the most recommended protocols of ingestion and its potential side effects.
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.[505][506][507] Postmenopausal women,[517] people with type II diabetes,[518] people on hemodialysis,[313] otherwise healthy elderly,[519] young people,[454][520][521] and athletes do not experience kidney damage either.[324] 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.[522][523][524][452][525][451][526][527] 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.[527] 

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.
Creatine has been investigated for its effects on depression, due to the significant changes occurring in brain morphology and neuronal structure associated with depression[246] and low brain bioenergetic turnover in depression[247], perhaps related to abnormal mitochondrial functioning, which reduces available energy for the brain.[248][249] The general association of low or otherwise impaired phosphate energy systems (of which creatine forms the energetic basis of) with depression, has been noted previously.[250][247][251] Due to associations with cellular death and impaired bioenergetics with depression, creatine was subsequently investigated.
In a mouse model of allergin-induced asthma, where mice were sensitized by ovalbumin for three weeks and then given 500mg/kg creatine, supplementation induced an increase in asthmatic hyperresponsiveness to low but not high doses of methacholine.[440] This hyperresponsiveness was associated with increased eosinophil and neutrophil infiltration into the lungs, and an increase in Th2 cell cytokines (IL-4 and IL-5) alongside an increase in IGF-1,[440] which is known to influence this process.[441] Interestingly, there was a nonsignificant increase in responsiveness in mice not sensitized to ovalbumin.[440]

A: At the end of the day, the most important variable regarding weight gain or loss is calorie consumption. However, meal frequency and timing around activity can both influence workout intensity and duration thus potentially allowing for further improvements in body composition. Remember, muscle growth isn’t a pulsatile process, it doesn’t just acutely spike and then return to baseline so if there aren’t circulating amino acids within the blood stream then they’ll have to be broken down from muscle as this is the highest form of concentrated amino acids within the body. That being said, it would probably be a good idea to consume anywhere from 3-6 meals spread throughout the day depending upon your schedule and preference. Ideally, we want to stimulate anabolism through food every 3-5 hours.
It is suggested [16,37] that another mechanism for the effect of creatine could be enhanced muscle glycogen accumulation and GLUT4 expression, when creatine supplementation is combined with a glycogen depleting exercise. Whereas it has been observed [38] that creatine supplementation alone does not enhance muscle glycogen storage. Hickner et al [15] observed positive effects of creatine supplementation for enhancing initial and maintaining a higher level of muscle glycogen during 2 hours of cycling. In general, it is accepted that glycogen depleting exercises, such as high intensity or long duration exercise should combine high carbohydrate diets with creatine supplementation to achieve heightened muscle glycogen stores [39].
This increased permeability is noted in glioma cells, where it exerts anti-cancer effects related to cell swelling,[99][100] and in other membranes, such as breast cancer cells[101] and skeletal (contractile) muscle cells.[102] The kinetics of cyclocreatine appear to be first-order,[101] with a relative Vmax of 90, Km of 25mM and a KD of 1.2mM.[103]
As mentioned, protein is essential for building muscle. If you are unable to consume the recommended amount of protein through diet alone, add protein powder for building muscle as a supplement. This applies to nearly anyone hoping to gain muscle mass since it’s not easy to pack in nearly 100 grams of protein a day through chicken, eggs and legumes alone. 

In regard to practical interventions, concurrent glycogen loading has been noted to increase creatine stores by 37-46% regardless of whether the tissue was exercised prior to loading phase.[176] It is important to note, however, that creatine levels in response to the creatine loading protocol were compared in one glycogen-depleted leg to the contralateral control leg, which was not exercised.[176] This does not rule out a possible systemic exercise-driven increase in creatine uptake, and the increase in creatine noted above[176] was larger than typically seen with a loading protocol (usually in the 20-25% range). Consistent with an exercise-effect, others have reported that exercise itself increases creatine uptake into muscle, reporting 68% greater creatine uptake in an exercised limb, relative to 14% without exercise.[153]
Creatine monohydrate is highly regarded as one of the most powerful and all-around best bodybuilding supplements for athletes hoping to make big gains fast. Creatine is one of the go-to supplements for building mass because it maximizes power output, strength, endurance, and overall performance, helping you to crush your fitness goals time and time again.

Glycogen synthesis is known to respond directly and positively to cellular swelling. This was demonstrated in an earlier study, during which rat muscle cells were exposed to a hypotonic solution in vitro to induce cell swelling, which increased glycogen synthesis by 75%. In contrast, exposing these same cells to a hypertonic solution hindered glycogen synthesis by 31%. These changes were not due to alterations in glucose uptake, but are blocked by hindering the PI3K/mTOR signaling pathway.[112] It was later noted that stress proteins of the MAPK class (p38 and JNK) as well as heat shock protein 27 (Hsp27) are activated in response to increasing osmolarity.[113][114] Furthermore, activation of MAPK signaling in skeletal muscle cells is known to induce myocyte differentiation[115] via GSK3β and MEF2 signaling, which can induce muscle cell growth.[116][117]
Recommended Dose: In Shannon Clark's article, "6 Ways To Get More Energized For Your Workouts", Dr. Chris Lockwood recommends between 1.36 and 2.5 milligrams of caffeine per pound of bodyweight. That would be 200-375 milligrams for a 150-pound person. If that leaves you jittery, try less. Determine your tolerance and find the dose that works best for you.
Taking high doses of creatine might harm the kidneys. Some medications can also harm the kidneys. Taking creatine with medications that can harm the kidneys might increase the chance of kidney damage.

Some of these medications that can harm the kidneys include cyclosporine (Neoral, Sandimmune); aminoglycosides including amikacin (Amikin), gentamicin (Garamycin, Gentak, others), and tobramycin (Nebcin, others); nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen (Advil, Motrin, Nuprin, others), indomethacin (Indocin), naproxen (Aleve, Anaprox, Naprelan, Naprosyn), piroxicam (Feldene); and numerous others.
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