Creatine is normally metabolized into creatinine (note the difference in spelling), which is eliminated by the kidneys under normal conditions. When the kidneys fail and cannot clear the blood as effectively, many metabolites get “backlogged” in the blood. Creatinine is easy to measure and as such it is a biomarker of kidney damage.[623][624] If serum creatinine levels are elevated, the doctor may suspect some kidney damage. Low-dose creatine (≤5 g/day) may not cause alterations in this biomarker in otherwise normal adults[524][625][525] but high doses of supplemental creatine may cause a false positive (an increase in creatinine, due to creatine turning into creatinine, which does not signify kidney damage) and is a diagnostic error.[520][518][626][523][517] Most studies, however, have noted only a small increase in creatinine levels even with doses ≈20 g/day.[524][626][627]
Creatine kinase enzymes (of which there are numerous isozymes) exist in both the mitochondria and the cytosol of the cell.[45][40] The four isozymes of creatine kinase include the Muscle Creatine Kinase (MCK), present in contractile muscle and cardiac muscle, and the Brain Creatine Kinase (BCK), expressed in neuron and glial cells and several other non-muscle cells. These two creatine kinases are met with Sarcolemmic Mitochondrial Creatine Kinase (sMitCK), expressed alongside MCK, and the ubiquitous Mitochondrial Creatine Kinase (uMitCK), which is expressed alongside BCK everywhere else.[25][39]
Carbohydrates play an important role for bodybuilders. They give the body energy to deal with the rigors of training and recovery. Carbohydrates also promote secretion of insulin, a hormone enabling cells to get the glucose they need. Insulin also carries amino acids into cells and promotes protein synthesis.[26] Insulin has steroid-like effects in terms of muscle gains.[27] It is impossible to promote protein synthesis without the existence of insulin, which means that without ingesting carbohydrates or protein—which also induces the release of insulin—it is impossible to add muscle mass.[28] Bodybuilders seek out low-glycemic polysaccharides and other slowly digesting carbohydrates, which release energy in a more stable fashion than high-glycemic sugars and starches. This is important as high-glycemic carbohydrates cause a sharp insulin response, which places the body in a state where it is likely to store additional food energy as fat. However, bodybuilders frequently do ingest some quickly digesting sugars (often in form of pure dextrose or maltodextrin) just before, during, and/or just after a workout. This may help to replenish glycogen stored within the muscle, and to stimulate muscle protein synthesis.[29]
After the ingestion of 5g creatine in otherwise healthy humans, serum levels of creatine were elevated from fasting levels (50-100µM) to 600-800µM within one hour after consumption.[135] The receptor follows Michaelis-Menten kinetics with a Vmax obtained at concentrations higher than 0.3-0.4mmol/L,[136] with prolonged serum concentrations above this amount exerting most of its saturation within two days.[137]
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.[245] 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[245]) 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.[245]

Another study demonstrated that females receiving 4 days of high-dose creatine intake (20 g/day) followed by low-dose creatine intake (5 g/day) during 10 weeks of resistance training (3hours/week) increased muscle PCr concentrations by 6%. Also, maximal strength of the muscle groups trained increased by 20-25%, maximal intermittent exercise capacity of the arm flexors increased by 10-25% and fat-free mass increased by 60% [11].


Carducci, C., Birarelli, M., Leuzzi, V., Carducci, C., Battini, R., Cioni, G., and Antonozzi, I. Guanidinoacetate and creatine plus creatinine assessment in physiologic fluids: an effective diagnostic tool for the biochemical diagnosis of arginine:glycine amidinotransferase and guanidinoacetate methyltransferase deficiencies. Clin Chem 2002;48:1772-1778. View abstract.

Before getting into the nitty-gritty details about supplements, it’s important to have a good understanding of how muscle growth works. When you take a muscle growth supplement, the role it plays in helping you reach your goals should be very clear. With the supplements available on the market, you can be sure that while some serve an important purpose, others are gimmicks. It’s easier to identify the money wasters if you know how muscle building works.
While they don’t play a big role, your body’s lean body mass and muscle strength is somewhat influenced by genetics. Actually, it’s good that they don’t have too much of an influence. Why? Because that means you have more of an influence on your muscle mass through your lifestyle. You can control it! If genetics were a determining factor, there wouldn’t be much you could do to change your situation.
2-4 Minutes Rest: Ideal for “tension exercises,” which includes most primary compound exercises. I personally take 3 minutes for the big stuff, sometimes going into the 3-4 minute range depending on exactly what I’m doing and what I feel like I need at the time. Since making strength gains is the main focus of these exercises, longer rest periods like this will be optimal for making it happen.
I get lost every time I walk into my neighborhood GNC… the people who work there know their stuff, but nobody knows my body better than me and that’s where it all falls apart, but I’m working on that. I agree, I rather have grass-fed and more natural options as opposed to anything containing GMO in the products… The point is to become healthier, not go the other way…. But I also don’t want to get too much soy in my diet either… My wife is doesn’t want it for me and it’s given me headaches too, so I’m not really one for those. I guess small amounts of soy should be okay, right? Could someone be allergic to soy? There’s tons of other options though and I’m going to have to really look more into these here coz it has everything I’ve been looking for! Thanks for putting this together!
A quantitative, comprehensive scientific summary and view of knowledge up to 2007 on the effects of creatine supplementation in athletes and active people was published in a 100 citation review position paper by the International Society of Sports Nutrition[5]. More recent literature has provided greater insight into the anabolic/performance enhancing mechanisms of creatine supplementation [15,25] suggesting that these effects may be due to satellite cell proliferation, myogenic transcription factors and insulin-like growth factor-1 signalling [16]. Saremi et al [26] reported a change in myogenic transcription factors when creatine supplementation and resistance training are combined in young healthy males. It was found that serum levels of myostatin, a muscle growth inhibitor, were decreased in the creatine group.
Parameters of lung function (main cause of death in ALS is declining respiratory function) have not benefited after creatine supplementation, and when quality of life is measured, there is no benefit either. Despite one study failing to find any significant differences in mortality risk, two other studies have suggested that creatine may reduce the risk. The results were nonsignificant, but due to all treatments being well tolerated it is thought that creatine may still play a role as an adjuvant.
Before getting into the nitty-gritty details about supplements, it’s important to have a good understanding of how muscle growth works. When you take a muscle growth supplement, the role it plays in helping you reach your goals should be very clear. With the supplements available on the market, you can be sure that while some serve an important purpose, others are gimmicks. It’s easier to identify the money wasters if you know how muscle building works.
Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) is a synthetic analogue of creatine in a cyclic form. It serves as a substrate for the creatine kinase enzyme system, acting as a creatine mimetic. Cyclocreatine may compete with creatine in the CK enzyme system to transfer phosphate groups to ADP, as coincubation of both can reduce cyclocreatine’s anti-motility effects on some cancer cells.[96]
I mean the first two ‘BS’ items focal point is lifting heavy, and then immediately the article goes into Step 1 – focus on 5-10 rep and 6-8 rep (heavier sets) — given we’re not powerlifting 1 rep or 3 rep max. Generally 6 rep sets we’re lifting heavy still… Does have a lot of good general info, but to me it almost feels like the bullet points of what supposedly not to do is actually a table of contents of what Jason is recommending we do do throughout the article…
One case study on a subject with a methylentetrahydrofolate reductase (MTHFR) 677TT homozygote, a relatively common genetic mutation known as “mild MTHFR deficiency,” which causes mild homocysteinemia,[310] has seen benefits due to creatine supplementation where homocysteine was approximately halved (49% reduction) while CT heterozygotes and CC homozygotes (n=9) were unaffected.[311] Additionally, one rat study suggested a possible role for creatine in reducing homocysteine levels in a model of high uric acid levels (model for end stage renal disease[312]) but this was not replicated when investigated in humans.[313]

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]


In humans, studies that investigate links between serotonin and creatine supplementation find that 21 trained males, given creatine via 22.8g creatine monohydrate (20g creatine equivalent) with 35g glucose, relative to a placebo of 160g glucose, was found to reduce the perception of fatigue in hot endurance training, possibly secondary to serotonergic modulation, specifically attentuating the increase of serotonin seen with exercise (normally seen to hinder exercise capacity in the heat[233]) while possibly increasing dopaminergic activity (conversely seen to benefit activity in the heat[234]).[155]
The creatine kinase (CK) enzyme in rat heart tissue appears to have a KM around 6mM of creatine as substrate.[280] and is known to positively influence mitochondrial function as higher cytoplasmic phosphocreatine concentrations (not so much creatine per se) increase the oxidative efficiency of mitochondria[280] This is thought to be due to the transfer of high energy phosphate groups.[280]
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.
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]

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]
^ Jump up to: a b c Brioche T, Pagano AF, Py G, Chopard A (April 2016). "Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention". Mol. Aspects Med. 50: 56–87. doi:10.1016/j.mam.2016.04.006. PMID 27106402. In conclusion, HMB treatment clearly appears to be a safe potent strategy against sarcopenia, and more generally against muscle wasting, because HMB improves muscle mass, muscle strength, and physical performance. It seems that HMB is able to act on three of the four major mechanisms involved in muscle deconditioning (protein turnover, apoptosis, and the regenerative process), whereas it is hypothesized to strongly affect the fourth (mitochondrial dynamics and functions). Moreover, HMB is cheap (~30– 50 US dollars per month at 3 g per day) and may prevent osteopenia (Bruckbauer and Zemel, 2013; Tatara, 2009; Tatara et al., 2007, 2008, 2012) and decrease cardiovascular risks (Nissen et al., 2000). For all these reasons, HMB should be routinely used in muscle-wasting conditions especially in aged people. ... 3 g of CaHMB taken three times a day (1 g each time) is the optimal posology, which allows for continual bioavailability of HMB in the body (Wilson et al., 2013).
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