Creatine supplements how they work simple,lower body workout routine gym,testosterone cypionate injection usp watson - PDF 2016

06.04.2014, admin  
Category: Nutrition Plan

Creatine (methylguanidine-acetic acid) is one of the most extensively studied dietary supplements available today.  It is a naturally occurring nitrogenous compound synthesized from the amino acids Glycine, Arginine, and Methionine and is present in relatively large quantities in most animal fleshes such as fish and red meat. In humans, the majority (~95%) of creatine is stored as phosphocreatine within muscle tissue, while much lesser amounts are present in the brain, liver, kidneys, and testes [1].  In the laboratory, creatine is synthesized from the reaction of N-methylglycine (also known as Sarcosine) and cyanamide [2]. Studies continued throughout the early 1900’s with researchers discovering the existence of phosphocreatine, and creatine kinase as well as the fact that creatine supplementation in animals increased muscle creatine content [1].  In 1923, Chanutin provided the first review of the fate of ingested creatine in man, describing the actions of tissue retention and influences upon creatinine production [3].
It was not until 1992 that the first study directly assessing the potential ergogenic effects of creatine was performed.  This study completed by Harris et al. This increase in popularity was met with an increase in research on the topic and today there are over 1000 peer reviewed scientific studies in regards to creatine supplementation. After over a century of use and research, creatine as a sports supplement is one of if not the most scientifically validated, safe, and effective ingredient in the sports nutrition industry. With the continuous growth of the dietary supplement and chemical synthesis industry, an increased demand has continually been met with an array of creatine supplements available for purchase on the market.  It is important to note that all of the previously mentioned creatine studies were performed on creatine monohydrate, which consists of creatine bound to one molecule of water. As encompassing all of the available literature on creatine monohydrate itself could span a textbook itself, only the most pertinent and comprehensive studies have been included in this review (mainly studies pertaining to common myths about creatine, and meta analyses).
Since the first study performed investigating the relationship between creatine supplementation and exercise performance up to the trials of today, monohydrate powder dominates the literature.  In an excellent review of the trials that have been completed, a leading authority in creatine research, Dr.
A 2003 meta analysis done by Branch on the effects of creatine supplementation in regards to body composition and performance discovered that effect size was significantly greater for changes in lean body mass, as well as upper body and repetitive bout laboratory based exercise.  This analysis pooled 96 peer reviewed studies in which a total of 1,847 subjects were randomized, blinded, and placebo controlled [7].
Regardless of the lack of reported side effects since the advent of creatine use, the long term safety remains a debated topic.  Oftentimes those in opposition of creatine supplementation cite the potential negative effects upon the kidneys as well as an increased risk of dehydration and muscle cramps.
To date, these concerns have not been validated in the literature, and the few reports that have attempted to make these associations have led to premature and sensationalized media conclusions.  For example, a 1998 case study published in The Lancet reported that a 25 year old male using creatine who possessed focal segmental glomerulosclerosis (scar tissue in the “filters” of the kidneys) and relapsing steroid responsive nephritic syndrome (high protein excretion in urine that favorably responds to corticosteroid treatment) experienced impaired renal function that was alleviated upon cessation of creatine use [14].


As expected, serum creatinine increased and creatinine clearance decreased, but all further measures of kidney function were not adversely affected or impaired such as proteinuria, albuminuria, serum urea, or electrolyte levels [18]. In regards to creatine and muscle dehydration, an excellent review of the available literature has been performed by Dalbo et al.  This publication examined all of the studies pertaining to the effects of creatine on fluid volume, fluid distribution, thermoregulatory responses, and supplementation in controlled hot or humid conditions as well as during exercise in dehydrated individuals. Of the 12 studies reviewed, not one suggested that ctreatine increases the risk of dehydration or muscle cramps.  Many of them actually suggested that it may decrease the risk as the creatine groups in many studies increased total body water, lowered core body temperature during exercise, and improved plasma volume (encouraged hyperhydration) [19]. Insulin and GLUT4 also appear to have additive effects upon creatine absorption into muscle, with studies that have provided carbohydrate and Alpha Lipoic Acid in addition to creatine resulting in greater intramuscular creatine stores [6].  Furthermore, response to creatine supplementation varies among individuals.
It has been concluded that those with lower initial intramuscular creatine stores, greater percentage of type 2 muscle fibers, greater muscle cross sectional area, and greater fat free mass generally respond better to supplementation [21]. Essentially, novel forms of creatine aim to capitalize on one or all of these four mechanisms mentioned:  Absorption, transport, tissue saturation, or contribution to ATP production. The premise behind the combination of creatine and organic acids is to provide additive ergogenic effects and improvement of biochemical properties such as aqueous solubility.  One potential drawback to this practice though, is that the incorporation of additional compounds will ultimately yield less pure creatine on a gram per gram basis. In the chemical synthesis industry, orotate is commonly used as a bioavailability enhancer and bound to minerals such as calcium, magnesium, potassium, zinc, etc…[28]  MAN Sports, the manufacturer who holds a patent on creatine orotate, claims that the addition of orotic acid further improves upon the ergogenic effects of creatine through maintaining intracellular ATP stores, elevating glycogen stores, and acting as a pH buffer and cell volumizer [29].  To date, none of these claims have been validated by peer reviewed scientific literature in humans. Creatine nitrate is relatively new to the market as are numerous new nitrate bound amino acid formulas.  The purported benefit behind the supplementation of nitrates is that they will lead to a subsequent increase in Nitric Oxide (NO) production, thus creating vasodilation and improving exercise performance through improved blood flow to active muscles. Though nitrate supplementation has recently been shown to reduce submaximal exercise oxygen demands as well as enhance exercise tolerance [30-31], no studies have directly analyzed the effects of creatine nitrate supplementation.
Compared to the placebo, both creatine groups significantly increased total work performed but there were no differences between groups on any other variables measured [34].
As the effects of creatine chelate supplements are not yet definitive, more work needs to be done to determine if a greater ergogenic benefit exists with their use.


Esterification is another process typically used in the pharmaceutical industry to increase the bioavailability of drugs with notoriously poor absorption.  Spillane et al. Creatinol-O-Phosphate is not actually creatine in a technical sense but is purported to act as its precursor, being metabolized within the body to form creatine [38].  A single study done in the seventies provided female patients with intramuscular and intravenous doses of creatinol and measured changes in handgrip strength. Creatinol administration did lead to significantly improved handgrip strength [39] but there exist numerous issues with attempting to apply these findings to athletic populations.  Most notably, that there was not a control or monohydrate group in the study and they did not orally ingest the supplement, rather, had injections. Polyethylene glycosylation is believed to positively alter permeability coefficients within the GI tract and muscle membrane, leading to enhanced absorption and tissue deposition [40]. PEGylation has been shown to positively alter many of the chemical properties of numerous pharmaceuticals, increasing their solubility, half-lifes, and resistance to alteration due to pH or temperature change [41].  It is interesting to note that it is also the major compenent in over-the-counter laxatives due to its water absorbent capacities [42].
PEGylated creatine is marketed as being superior to monohydrate in that smaller doses can be used to create the same ergogenic effects.
Although the aqueous solubility of creatine can be improved, and plasma creatine may be slightly increased with novel forms of creatine, these have not proven to lead to any measureable differences in exercise performance when compared to monohydrate.  Creatine bound to metabolic intermediatesmay confer some additional endurance exercise benefits but it must be stressed that this process leads to less pure creatine on a gram per gram basis. Alternative forms that possess some slight supporting evidence include creatine chelate, PEG creatine and certain creatine salts. Richard Kreider, has concluded, “of the approximately 300 studies that have evaluated the potential ergogenic value of creatine supplementation, about 70% of these studies report statistically significant results while remaining studies generally report non-significant gains in performance” [6].



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