The first open label trial on ALS failed to significantly alter lung function as assessed by FEV (when comparing the rate of decline pretreatment relative to treatment).[545] Creatine has elsewhere failed to benefit lung function at 5g daily for months relative to control[546] and failed to significantly attenuate the rate of lung function deterioration over 16 months at 10g daily[505] and 5g daily over nine months.[507]
In regard to the loading period, two reviews suggest that the range of weight gain associated with creatine supplementation at 20g for 7 days is in the range of 0.9-1.8kg (1.98-3.96lbs).[612][613] The highest reported increase in water weight associated with creatine loading, although measured a month after loading started (after a maintenance phase) was 3.8kg (8.36lbs).[614]
Mitochondrial myopathies are a subgroup of mitochondrial cytopathies in which the skeletal muscle is negatively influenced. They are characterized by weaknesses in muscular function and energy metabolism.[547] These particular myopathies are thought to benefit from creatine supplementation, since creatine can help with some of the dysregulated energy production.[548]
While the number of reps you do per set is important, of equal importance is the total number of reps you do per muscle group. The National Strength and Conditioning Association has determined that, to maximize growth, you need approximately 20–70 total reps per muscle group. Depending on which end of a rep range you’re working, this can be done in one session or over a few days (a training week, for instance), but that’s the spread you need to cover to see gains.
Creatine supplementation in the under 18 population has not received a great deal of attention, especially in regards to sports/exercise performance. Despite this, creatine is being supplemented in young, <18 years old, athletes [52,53]. In a 2001 report [52] conducted on pupils from middle and high school (aged 10 – 18) in Westchester County (USA) 62 of the 1103 pupils surveyed were using creatine. The authors found this concerning for 2 main reasons: firstly, the safety of creatine supplementation is not established for this age group and is therefore not recommended. Secondly, it was speculated that taking creatine would lead on to more dangerous performance enhancing products such as anabolic steroids. It is important to point out that this potential escalation is speculation. Furthermore, a questionnaire was used to determine creatine use amongst this age group and does not necessarily reflect the truth.
Injections of creatine are known to be neuroprotective against low oxygen levels (hypoxia) even to neonatal rats.[532] This is thought to be associated with the increased collective pool of phosphocreatine and creatine.[236] Since oral ingestion of creatine by the mother increases brain concentrations of creatine by 3.6% in the fetus prior to birth,[531] it is thought to be protective in the fetuses subject to hypoxic (low oxygen) stressors, such as a caesarean section.
A good way to determine how much fat in grams you should be taking in is to multiply your calorie intake by 0.001 for maximum trans-fats; by 0.008 for maximum saturated fats; and by 0.03 for the "good fats". For example, for a 2,500-calorie diet, you would limit trans-fats to 3g or less, saturated fats to 20g or less, and up to 75g of mono- and polyunsaturated fats.
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. 

A maintenance phase of 2g daily appears to technically preserve creatine content in skeletal muscle of responders either inherently or after a loading phase, but in sedentary people or those with light activity, creatine content still progressively declines (although it still higher than baseline levels after six weeks) and glycogen increases seem to normalize. This maintenance dose may be wholly insufficient for athletes, a 5g maintenance protocol may be more prudent.
Without supplementation, approximately 14.6mmol (2g) of creatinine, creatine’s urinary metabolite, is lost on a daily basis in a standard 70kg male ages 20-39. The value is slightly lower in females and the elderly due to a presence of less muscle mass.[35] This amount is considered necessary to obtain in either food or supplemental form to avoid creatine deficiency. Requirements may be increased in people with higher than normal lean mass.[35][198] Creatine excretion rates on a daily basis are correlated with muscle mass, and the value of 2g a day is derived from the aforementioned male population with about 120g creatine storage capacity.[35] Specifically, the rate of daily creatine losses is about 1.6%[199]-1.7%,[25] and mean losses for women are approximately 80% that of men due to less average lean mass.[35] For weight-matched elderly men (70kg, 70-79 years of age) the rate of loss of 7.8mmol/day,[49] or about half (53%) that of younger men.

A study showed that 100mg/kg creatine monohydrate daily over four months supplemented by boys with DMD is able to enhance handgrip strength in the dominant hand only (less than 10% increase) and increase whole-body lean mass. While the trend toward whole body strength reduction seen in placebo was ablated and there was no interaction with corticosteroids,[560] this study failed to find an influence on activities of daily living or lung function.[560] Elsewhere in children not on corticosteroids with DMD, supplementation of 5g creatine for eight weeks was confirmed to increase muscular phosphocreatine content[554] and according to a manual muscle test (MMT) there was a significant improvement in muscular function relative to placebo, with more parents reporting benefit with creatine (53.8%) relative to placebo (14%).[554]

Although some have voiced concerns about kidney damage with creatine supplementation, it’s generally regarded as a safe supplement when taken responsibly. The Mayo Clinic advises against taking it if you have an allergy. When used properly, the incidence of potential side effects such as low blood sugar and dehydration, are minor in healthy people taking a safe dosage.
Nephrectomized rats may have significantly reduced creatine synthesis rates[509] via impairment of methylation (the GAMT enzyme)[510] although creatine reuptake from the urine seems unimpaired.[511] Supplemental creatine in a rat model of 2/3rds nephrectomy (2% creatine in the diet) does not appear to negatively influence kidney function as assessed by the serum biomarkers of cystatin C and urinary protein or creatinine clearance rates.[512] Elsewhere, 2% creatine in the diet in rats for two weeks again failed to show negative effects on kidney function, but showed benefit in reducing homocysteine in late-stage uremic rats.[312] While there is not much human evidence for the rat nephrectomy model, a lone case study in a man with a single kidney failed to find an impairing effect of creatine (20g daily for five days and 5g for another month) in conjunction with a high protein diet.[513]

The concentration in healthy controls (57+/-8 years) without supplementation of creatine appears to be around 1.24+/-0.26µM per gram of hemoglobin[292] and appears to decrease in concentration during the aging process of the erythrocyte.[294][295][296] Otherwise healthy subjects who take a loading phase of creatine (5g four times daily for five days) can experience a 129.6% increase in erythrocytic creatine concentrations from an average value of 418µM (per liter) up to 961µM with a large range (increases in the range of 144.4-1004.8µM),[297] and this effect appears to correlate somewhat with muscular creatine stores.[297]
Activation of NMDA receptors is known to stimulate Na+,K+-ATPase activity[218] secondary to calcineurin,[219] which which has been confirmed with creatine in hippocampal cells (0.1-1mM trended, but 10mM was significant). This is blocked by NMDA antagonists.[220] This increase in Na+,K+-ATPase activity is also attenauted with activation of either PKC or PKA,[220] which are antagonistic with calcineurin.[219][221]

Macrophages are known to express creatine kinase[290] and take creatine up from a medium through a sodium dependent mechanism (likely the creatine transporter) in a saturable manner,[435] with a second component that requires there to be no concentration gradient to work against (likely passive diffusion) but this effect tends to only account for up to 10% of total uptake in the physiological range (20-60µM).[435] Supraphysiological range was not tested.
Creatine ethyl ester is more a pronutrient for creatinine rather than creatine,[74] and was originally created in an attempt to bypass the creatine transporter. It is currently being studied for its potential as a treatment for situations in which there is a lack of creatine transporters (alongside cyclocreatine as another possible example).[77] Its efficacy may rely on intravenous administration, however.
Heath suggests incorporating dropsets into your training routine by immediately decreasing the weight and repping out again to failure. “Dropsets overload the muscle with shorter rest periods and increasing volume which you need to grow,” says Heath. “That overload improves your body’s abilities to utilize more nutrients, natural growth hormone, and natural testosterone into those areas and makes the supplements you take more effective.” Heath’s favorite way to do dropsets is on a pin-loaded machine since it’s faster to switch weights.
You don’t have to, but you can. The typical creatine dose is 5 grams once or twice per day, but it’s sometimes suggested that one should “load” creatine by taking 20 to 25 grams per day for the first week of usage. This is then followed with 3 to 4 weeks of 5 grams per day, then a break for a week or two, then repeat. This may bring about more acute increases in strength and muscle size — creatine will “work” more quickly, in other words — but it’s not necessary.
When assessing the antioxidant effects of creatine, it does not appear to sequester superoxide and may not be a direct antioxidant.[241] Additionally, creatine failed to protect neurons from H2O2 incubation to induce cell death via pro-oxidative means.[241] These results are in contrast to previously recorded results suggesting creatine acts as a direct anti-oxidant.[242]

Small but significant is good. It’s especially helpful during short periods of extremely powerful physical activity, particularly if those short bursts of activity are repeated, as in weightlifting, sprinting or football, for example. The study also says that creatine supplementation is associated with enhanced strength gains in strength training programs, which could be related to the greater volume and intensity of training that you can achieve when you’re taking creatine supplements. Plus, according to the study, there’s no evidence of gastrointestinal, renal or muscle cramping complications – more good news.
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.[147][148] The 73kDa band has been reported to be the predominant band in humans, with no differences based on gender.[148] 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.[149]
Perform the two workouts (Day 1 and 2) once each per week, resting at least a day between each. Perform the exercises marked with letters as a group. Do one set of A, rest, then one set of B, rest (note that some groups have an exercise “C”), and repeat until all sets are complete. Then go on to the next group. Perform three sets of 8–10 reps for each exercise. After a month, you’ll see how rewarding just a months in the gym can be.
No need to worry! This myth that caffeine counteracts creatine came from the simple, but wrong logic that because caffeine accelerates the nervous system and uses more water, it would counteract creatine because creatine helps your body retain water. While both of these statements are true, it does not mean they “cancel” eachother out, all that it means is that your body will be able to stay hydrated longer if you are taking creatine and caffeine opposed to just taking caffeine.
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.
^ Jump up to: a b c d e f g h Momaya A, Fawal M, Estes R (April 2015). "Performance-enhancing substances in sports: a review of the literature". Sports Med. 45 (4): 517–531. doi:10.1007/s40279-015-0308-9. PMID 25663250. Wilson et al. [91] demonstrated that when non-resistance trained males received HMB pre-exercise, the rise of lactate dehydrogenase (LDH) levels reduced, and HMB tended to decrease soreness. Knitter et al. [92] showed a decrease in LDH and creatine phosphokinase (CPK), a byproduct of muscle breakdown, by HMB after a prolonged run. ... The utility of HMB does seem to be affected by timing of intake prior to workouts and dosage [97].
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