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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]
In vitro, creatine (0.125mM or higher) can reduce excitotoxicity from glutamate, which is thought to be secondary to preserving intracellular creatine phosphate levels.[209] Glutamate-induced excitotoxicity is caused by excessive intracellular calcium levels resulting from ATP depletion. Since high levels of calcium inside the cell are toxic, ATP preserves membrane integrity,[210] in part by promoting calcium homeostasis. When ATP is depleted, the sodium-potassium ATPase pump (Na+,K+-ATPase) stops working, leading to sodium accumulation in the cell. This reduces the activity of the sodium-calcium exchange pump, which, alongside a lack of ATP, reduces calcium efflux through the Na+,K+-ATPase. Thus, ATP depletion leads to intracellular calcium overload, loss of membrane potential, and excitotoxic cell death. Therefore, by helping preserve ATP levels, creatine is protective against excitotoxicity. This protective effect was noted after either creatine preloading or addition up to 2 hours after excitotoxicity.[209] Protection from glutamate-induced toxicity also extends to glial cells[211] and is additive with COX2 inhibition.[212]

If you’re a beginner, you should train with three full-body workouts per week. In each one, do a compound pushing movement (like a bench press), a compound pulling movement (like a chinup), and a compound lower-body exercise (squat, trap-bar deadlift, for example). If you want to add in 1–2 other exercises like loaded carries or kettlebell swings as a finisher, that’s fine, but three exercises is enough to work the whole body.
Syrotuik and Bell [57] investigated the physical characteristics of responder and non-responder subjects to creatine supplementation in recreationally resistance trained men with no history of CM usage. The supplement group was asked to ingest a loading dosage of 0.3 g/kg/d for 5 days. The physiological characteristics of responders were classified using Greenhaff et al [58] criterion of >20 mmol/kg dry weight increase in total intramuscular creatine and phosphocreatine and non responders as <10 mmol/kg dry weight increase, a third group labeled quasi responders were also used to classify participants who fell in between the previously mentioned groups (10-20 mmol/kg dry weight). Overall, the supplemented group showed a mean increase in total resting muscle creatine and phosphocreatine of 14.5% (from 111.12 ± 8.87 mmol/kg dry weight to 127.30 ± 9.69 mmol/kg dry weight) whilst the placebo group remained relatively unaffected (from 115.70 ± 14.99 mmol/kg dry weight to 111.74 ± 12.95 mmol/kg dry weight). However when looking at individual cases from the creatine group the results showed a variance in response. From the 11 males in the supplemented group, 3 participants were responders (mean increase of 29.5 mmol/kg dry weight or 27%), 5 quasi responders (mean increase of 14.9 mmol/kg dry weight or 13.6%) and 3 non-responders (mean increase of 5.1 mmol/kg dry weight or 4.8%). Using muscle biopsies of the vastus lateralis, a descending trend for groups and mean percentage fiber type was observed. Responders showed the greatest percentage of type II fibers followed by quasi responders and non-responders. The responder and quasi responder groups had an initial larger cross sectional area for type I, type IIa and type IIx fibers. The responder group also had the greatest mean increase in the cross sectional area of all the muscle fiber types measured (type I, type IIa and type IIx increased 320, 971 and 840 μm2 respectively) and non-responders the least (type I, type IIa and type IIx increased 60, 46 and 78 μm2 respectively). There was evidence of a descending trend for responders to have the highest percentage of type II fibers; furthermore, responders and quasi responders possessed the largest initial cross sectional area of type I, IIa and IIx fibers. Responders were seen to have the lowest initial levels of creatine and phosphocreatine. This has also been observed in a previous study [17] which found that subjects whose creatine levels were around 150 mmol/Kg dry mass did not have any increments in their creatine saturation due to creatine supplementation, neither did they experience any increases of creatine uptake, phosphocreatine resynthesis and performance. This would indicate a limit maximum size of the creatine pool.
Exercise is highly effective in increasing your lean body mass, which is essentially muscle. In a study published in 2012, progressive resistance training helped men ages 50 to 83 gain an average of 2.4 pounds of lean body mass over an average of 20.5 weeks. Progressive resistance training involves performing weight bearing exercises. In addition, you must slowly increase the challenge of the exercise over time by increasing the weight, reps and/or sets. Studies show that either increasing reps or weight amount will work. So, if you don’t want to lift more weight, you can just do more reps and still build muscle.
Duchenne’s Muscular Dystrophy (DMD) is associated with a reduction in intracellular creatine stores[554] known to only affects males. It is an X-linked progressive myopathy associated with abnormalities in the dystrophin gene.[555] The standard therapy at this moment involves corticosteroids such as prednisone.[556][557] Creatine is thought to be therapeutic since the known targetable abnormalities in DMD (impairment in protein synthesis associated with oxidative stress and increased protein breakdown) is a property of creatine and supplementation showed promise in the first case study[558] and benefit in a group of mixed dystrophinopathies.[559]
Without supplementation, creatine is formed primarily in the liver, with minor contributions from the pancreas and kidneys. The two amino acids, glycine and arginine, combine via the enzyme Arginine:Glycine amidinotransferase (AGAT) to form ornithine and guanidoacetate. This is the first of two steps in creatine synthesis, and although rare, any deficiency of this enzyme can result in mild mental retardation and muscular weakness.[28] AGAT is also the primary regulatory step, and an excess of dietary creatine can suppress activity of AGAT to reduce creatine synthesis[29] by reducing AGAT mRNA levels, rather than resulting in competitive inhibition.[30]
The type of exercise performed also depends on the individual's goals. Those who seek to increase their performance in sports would focus mostly on compound exercises, with isolation exercises being used to strengthen just those muscles that are holding the athlete back. Similarly, a powerlifter would focus on the specific compound exercises that are performed at powerlifting competitions. However, those who seek to improve the look of their body without necessarily maximizing their strength gains (including bodybuilders) would put more of an emphasis on isolation exercises. Both types of athletes, however, generally make use of both compound and isolation exercises.

Most of us have lives, or jobs, or school, or family, or whatever else that puts some kind of limit on when and how often we can work out. For example, are there certain days that you are able to work out on, and certain days you aren’t? Are you able to train 5 days per week, or would 3-4 be more ideal? Choosing a split that suits your personal schedule and is as convenient for you as possible will be crucial for adherence, and without adherence, nothing is going to work.
Liquid creatine has been shown to be less effective than creatine monohydrate.[69] This reduced effect is due to the passive breakdown of creatine over a period of days into creatinine, which occurs when it is suspended in solution.[70] This breakdown is not an issue for at-home use when creatine is added to shakes, but it is a concern from a manufacturing perspective in regard to shelf-life before use.
One pilot study using 150mg/kg creatine monohydrate for a five day loading phase followed by maintenance (60mg/kg) for the remainder of the five weeks noted that supplementation was associated with fewer muscle symptoms and complaints alongside improved muscular function,[572] yet a later trial trying to replicate the obsevations using 150mg/kg daily for five weeks noted the opposite, that creatine supplementation exacerbated symptoms.[573]