How To Take Creatine

Creatine Practical Guide.

Creatine: A practical guide evolved from the thousands of questions asked by professional and amateur athletes from around the globe. Learn How To Most Effectively Combine Exercise, Nutrition And Smart Creatine Use For Explosive Muscle Growth And Improved Overall Health. Here is just a small sampling of the many questions addressed by this e-book How long can I keep creatine on the shelf? Will I lose muscle after I stop supplementing? Not all creatine brands recommend the same amount. What gives? Is mixing creatine with protein powder a bad idea? Why do so many creatine brands contain so much dextrose? Is loading really necessary? Im currently taking Accutane for nodular acne. Is it safe for me to supplement? Will creatine stunt my growth? Im training twice as much these days and Im still not making any gains! Why? If creatine isnt a steroid, then how come it gave me a positive doping result? Will creatine shrink my package?!

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Muscle Enzymes Creatine Kinase and Aldolase

Creatine kinase (CK) is an enzyme produced by skeletal muscles, the heart muscle, and the brain. Although it may be elevated in adults who have recently suffered a heart attack, the most frequent cause of elevations in childhood is muscle inflammation. This may occur in children with dermatomyositis, scleroderma, or mixed connective tissue disease. Sometimes the CK is elevated with extensive exercise, but in these children the level goes back to normal after two weeks' rest. The level of CK is also elevated after some viral infections. Some children have elevated CK levels that persist despite rest and for which no explanation can be found see Chapter 14, on dermatomyositis.


Historical note Creatine was first discovered in 1832 when it was identified in meat. The word creatine is derived from the Greek kreasior flesh, similar to the word 'creature'. About 1 5 years later, the meat from foxes killed in the wild were found to have 1 0-fold more creatine than meat from domesticated foxes, suggesting that physical exercise must influence the amount of creatine that accumulates in muscles. Early last century orally consumed creatine was shown to be partly retained in the body and able to increase creatine content in muscles, leading some to suspect this could influence the performance of muscles. Nowadays, creatine monohydrate enjoys enormous popularity as a sports supplements and is being recommended to elite athletes by respected sporting bodies such as the Australian Institute of Sport (AIS).

Creatine Monohydrate

One compound that has received critical acclaim in the past few years is Creatine Monohydrate. Creatine is a metabolite found naturally in red meats which regenerates ATP, the high powered chemical that supplies energy for the initial seconds of muscle contraction. The effects of creatine have been documented in dozens of scientific studies and include increased strength, power, weight gain, and recovery time. Creatine is unquestionably the hottest supplement in the sports nutrition world today and is being used widely by sprinters, bicyclists, football players, boxers, powerlifters, bodybuilders, and virtually every other athlete who requires strength and power. Supplemental creatine is available in a tasteless and odorless powder which is usually consumed mixed in water or juice. The recommended amount is 4-6 teaspoons per day for the first 5 days (loading phase), then 2-3 teaspoons per day thereafter for maintenance.

Hepatic Cirrhosis and Encephalopathy

MR spectroscopy has been characterized as an ideal modality for evaluating CHE because it is capable of monitoring neurochemical events related to the pathogenesis of the disorder (Seery and Taylor-Robinson, 1996). Kreis and coworkers (1992) reported increased parietal cortex glutamine (Glx) levels and decreased myo-inositol (ml) and choline levels (Cho) in CHE (Kreis et al., 1992). Subsequently, reduced parietal white matter Cho total creatine (Cr), parietal white and occipital gray matter

Fetal Alcohol Exposure

Mimic in the laboratory, a nonhuman primate study of controlled fetal alcohol exposure documented normal brain morphology (Astley et al., 1995). However, that study also reported elevated basal ganglia 1H MRS choline (Cho) over total creatine (Cr) ratios, as well as associations between Cho Cr ratios and both duration of alcohol exposure and degree of developmental impairment (Astley et al., 1995).

Background And Relevant Pharmacokinetics

Creatine is a naturally occurring nitrogenous compound produced in the human liver, pancreas and kidneys at a rate of 1-2 g daily. It is synthesised from the amino acids glycine, arginine and methionine and stored primarily in skeletal muscle, where it is in dynamic equilibrium with phosphocreatine and is a precursor to adenosine triphosphate (ATP), the main source of energy for muscle activity and many other biological functions. Orally ingested creatine is absorbed from the small intestine, then distributed via creatine transporters around the body to muscles and nerves (Persky et al 2003). These transporters also serve as a clearance mechanism because of creatine 'trapping' by skeletal muscle. It is ultimately converted to creatinine and excreted by the kidneys.

Deficiency Signs And Symptoms

Several rare inborn errors of metabolism that result in a lack of creatine and phosphorylcreatine in the brain and severe mental retardation have been identified. Other symptoms and signs, such as involuntary extrapyramidal movements, speech People involved in intense physical activity, vegetarians and those with muscle diseases may have lowered creatine levels.

Congestive Heart Failure

Muscle fatigue due to loss of skeletal muscle mass and strength, decreased oxidative capacity and other abnormalities of muscle metabolism have been associated with congestive heart failure. As a result, creatine supplementation has been suggested as a possible therapeutic agent in this condition. A dose of 10 g creatine daily for 7 days significantly increased exercise capacity and muscle strength compared to placebo in a double-blind study involving 17 men with congestive heart failure (Gordon et al 1995). However, creatine supplementation did not alter ejection fraction at rest or at work. Muscle endurance during handgrip exercises was also seen to improve in another double-blind, crossover study of 20 men given 5 g creatine four times daily for 5 days (Andrews et al 1998).

Neurological Degenerative Diseases

Over the past few years, a considerable body of scientific evidence has given support to the idea that creatine supplementation may alleviate some of the clinical symptoms of neurological disease and delay disease progression (Wyss & Schulze 2002). Studies conducted in both animal models of neurodegenerative disease and humans have produced mixed results. Huntington's disease A number of studies conducted with experimental animal models of Huntington's disease have identified a possible role for creatine supplementation (Andreassen et al 2001, Dedeoglu et al 2003, Ferrante et al 2000). Creatine was shown to increase survival, delay onset of symptoms and exert neuroprotective effects in vivo. Motor neuron disease A preliminary study demonstrated that creatine supplementation of 20 g daily for 7 days followed by 3 g daily for 3 and 6 months produced temporary increases in maximal isometric power in patients with MND (Mazzini et al 2001). More recently, two randomised, double blind,...

Neuroprotective Effects

Poorly performing sports horses, which were found to be associated with long-lasting high serum activities of g-glutamyltransferase (GGT), glutamate-oxaloacete transaminase (GOT), and creatine phosphokinase (CPK) (62), were orally administered with 3 g day of the lignan-containing

Nonprotein Pathways of Amino Acid Nitrogen Utilization

Although in general the utilization of dietary amino acids is dominated by their incorporation into protein and their role in energy metabolism, amino acids are also involved in the synthesis of other nitrogenous compounds important to physiological viability as shown in Table 10-5. Some pathways have the potential for exerting a substantial impact on the utilization of certain amino acids, and may be of potential significance for the requirements for these amino acids. This is particularly true for glycine, which is a precursor for six nitrogenous compounds, as shown in Table 10-5. Its utilization in the synthesis of creatine (muscle function), heme (oxygen transport and oxidative phosphorylation), and glutathione (protective reactions which are limited by the amount of available cysteine) is not only of physiological importance, but can also involve substantial quantities of the amino acid. For example, in the absence of a dietary source of creatine, adults require at least 1.1 g d...

Infants Ages 0 Through 6 Months Method Used to Set the Adequate Intake

The protein content of human milk at various stages of lactation is shown in Table 10-7. In general, protein concentrations decline in the later stages of lactation. Nonprotein nitrogen contributes 20 to 27 percent of total milk nitrogen (Atkinson et al., 1980 Butte et al., 1984a, 1984b Dewey et al., 1996). These nonprotein nitrogenous components include free amino acids, pyrimidine nucleotides, creatine, and glutathione, but the large majority is urea. Using data from 13 lactating mothers of term infants, Butte and coworkers (1984a) reported that the protein content of human milk was 1.29 g dL at 2 weeks of lactation, 1.08 g dL at 4 weeks, 1.01 g dL at 6 weeks, 0.94 g dL at 8 weeks, and 0.91 g dL from 10 to 12 weeks. Similar results of 0.91 g dL were reported by Lammi-Keefe and coworkers (1990) at 8 weeks of lactation in 6 mothers of term infants. Both of these studies analyzed nitrogen by the Kjeldahl method. However, higher human milk protein content has been reported by Nommsen...

Loss of Lean Body Mass

Document the loss of muscle mass over an extended period of time. Dietary creatine and creatinine intake has only a minor influence (< 20 ) on urinary creatinine in the normal eating individual. Changes in dietary intake may influence the accuracy of the collection, but repeating the values over 3 days will help average variations in dietary intake. Impairment of renal function reduces the normal creatinine excretion and excludes the creatinine height index as a marker of muscle mass.

Fuel Used During Exercise

You may have heard about two of the chemicals involved in the production of ATP without oxygen creatine phosphate and lactic acid. Creatine phosphate is present in the muscles and is used to make ATP rapidly. Creatine phosphate can make enough ATP to last for 30 seconds worth of exercise. To try and increase the amount of ATP that can be made from creatine phosphate, some people take creatine supplements. However, the research is not conclusive as to the benefits of taking creatine and the long-term risks are not known (see Chapter 14). Furthermore, your body makes creatine and it is obtained in the diet from meats. The second chemical is lactic acid. When maximal or near maximal exercise continues beyond 30 seconds, the muscle must use glucose (a simple CHO) to produce ATP. During this anaerobic energy process, the by-product lactic acid is formed. Small amounts of lactic acid can be converted back into glucose and then broken down again to form more ATP. However, as exercise...

Nitrogen Versus Amino Acids

Absorbed nitrogen is mainly in the form of amino acids, but a proportion is in other compounds such as nucleic acids, creatine, amino sugars, ammonia, and urea. The quantitative extent to which these contribute to nitrogen retention and homeostasis is not known. Creatine can probably be utilized (Metges et al., 1999b), but in general it is unknown to what extent these different compounds can have a sparing effect on the utilization of the amino acids for which they are precursors. However, the major requirement for total nitrogen or protein is for the specific indispensable amino acids (and or conditionally indispensable amino acids) and an additional source of a-amino nitrogen. At appropriate intakes these maintain protein homeostasis and adequate synthesis of those physiologically important compounds for which amino acids are the obligatory precursors (Table 10-5).

Nutritional summary

Function Folate mediates the transfer of one carbon in numerous reactions including the synthesis of purine nucleotides, amino acids, carnitine, creatine, lipids, hormones, and also serves as a cofactor for proteins involved in the control of cireadian rhythm. Requirements Adults should get at least 400 fig, d. Women who may become pregnant should use a supplement with this amount. Needs during pregnancy and breastfeeding are slightly higher.

Estrogenlike Activity Of Licorice Root Extract

The effect of licorice extract, glabridin, and estradiol feeding on the induction of creatine kinase activity in ovariectomized female rat tissues. Rats were fed with 0.5 Ag day rat of estradiol, 25 Ag day rat of licorice extract, or 25 Ag day rat of glabridin for 4 weeks. CK activity was tested in various selected tissues. The effect of licorice extract, glabridin, and estradiol feeding on the induction of creatine kinase activity in ovariectomized female rat tissues. Rats were fed with 0.5 Ag day rat of estradiol, 25 Ag day rat of licorice extract, or 25 Ag day rat of glabridin for 4 weeks. CK activity was tested in various selected tissues. with prostate cancer (37), which was attributed to licochalcone A present in the extract. The estrogen-like effects of licorice extract in vivo were tested in our laboratory (38). Ovariectomized female rats fed with licorice extract (25 Ag day rat) or estradiol (0.5 Ag day rat) for 4 weeks showed a significant increase in creatine kinase (CK)...

Antinephritic Activity

Aceteoside, given from the first day after i.v. injection of anti-GBM serum, inhibits protein excretion into urine on crescentic-type anti-GBM nephritis in rats. In the acteoside-treated rats, cholesterol and creatine contents and antibody production against rabbit g-globulin in the plasmas were lower than those of the nephritic control rats. Histological observation demonstrated that this agent suppresses hyper-cellularity and crescent formation, adhesion of capillary wall to Bowman's capsule, and fibrinoid necrosis in the glomeruli. Furthermore, rat IgG and C3 deposits on the GBM were significantly less in the acteoside-treated group than in the control nephritic group. When the treatment was started from the twentieth day after i.v. injection of anti-GBM serum, by which time the disease had been established, aceteoside resulted in a similar effect on the nephritic rats as stated above. These results suggest that aceteoside may be a useful...

Neuroleptic Malignant Syndrome

Chiatric illness, for example, rigidity dystonia can be confused with simple dystonia or with EPS. Mutism can be a sign of severe psychosis or catatonia alone, although this does occur with NMS. Behavioral features such as agitation can also overlap with other psychiatric syndromes however, the presence of delirium or seizures is a harbinger of more serious general medical illness (including drug withdrawal) or NMS. Laboratory findings may reveal an increased creatine kinase secondary to myonecrosis from sustained muscular rigidity. Liver enzymes may be elevated, but their relation to NMS is unclear. Leukocytosis is also often present. Treatment of this potentially fatal disorder is largely supportive. Specific interventions include discontinuation of antipsychotics (an option that may take a long period of time in individuals treated with depot antipsychotics) dantrolene (a muscle relaxant) is used to treat rigidity and decrease myonecrosis and bromocriptine (a dopamine agonist) is...

Xiicurcumin Protects Against Cataract Formation

Cardiotoxicity is one of the major problems associated with administration of most chemotherapeutic agents. Venkatesan examined the protective effect of curcumin on acute Adriamycin (ADR) myocardial toxicity in rats (116). ADR toxicity, induced by a single intraperitoneal injection (30 mg kg), was revealed by elevated serum creatine kinase (CK) and LDH. The level of the lipid peroxidation products, conjugated dienes and malondialdehyde, was markedly elevated by ADR. ADR caused a decrease in myocardial glutathi-one content and glutathione peroxidase activity and an increase in cardiac catalase activity. Curcumin treatment (200 mg kg) 7 days before and 2 days (after administration of) ADR significantly ameliorated the early manifestation of cardiotoxicity (ST-segment elevation and an increase in heart rate) and prevented the rise in serum CK and LDH exerted by ADR. ADR-treated rats that received curcumin displayed a significant inhibition of lipid peroxidation and augmentation of...

The Possible Essentiality of Choline

14.3 CREATINE Creatine functions as a phosphagen in muscle. Neither the small amount of ATP in muscle nor the speed with which metabolic activity can be increased, and hence ADP be rephosphorylated, matches the demand for ATP for rapid or sustained muscle contraction. Muscle contains a relatively large amount Figure 14.5. Synthesis of creatine. Glycine guanidotransferase (amidinotransferase),EC guanidinoacetate methyltransferase, EC and creatine kinase, EC Figure 14.5. Synthesis of creatine. Glycine guanidotransferase (amidinotransferase),EC guanidinoacetate methyltransferase, EC and creatine kinase, EC of creatine phosphate (aboutfour-foldhigherthan ATP). This acts as a reservoir or buffer to maintain a supply of ATP for muscle contraction until metabolic activity increases. Creatine is not a dietary essential as shown in Figure 14.5, it is synthesized from the amino acids glycine, arginine, and methionine. However, a single serving...

Static Biochemical Tests

Urinary creatinine, usually measured with a colo-rimetric method (also automated), is used as a biochemical marker of muscle mass. In fact, urinary creatinine is a nonenzymatic product of creatine and cannot be reutilized. Various assumptions are required for correct urinary creatinine determination, and various confounding effects are reported (age, diet, intensive exercise, pregnancy, injury, fever, and renal diseases with impaired creatinine clearance). In a clinical setting, the creatinine height index is preferred, but because of some limitations, it is not very useful.

Dermatomyositis and Polymyositis

The diagnosis of dermatomyositis is made on the basis of the history and the physical examination findings plus appropriate blood tests. Either the creatine kinase (CK) or the aldolase level will be abnormal in most children with der-matomyositis. These tests indicate muscle inflammation, but they can also be abnormal following viral infections or extensive physical activity (e.g., playing football, running track, lifting weights). Often these tests are not included in the routine chemistry panel and have to be specifically ordered by the physician. All of the routine tests, including the erythrocyte sedimentation rate, might be normal despite active dermatomyositis.

Arginine Citrulline Ornithine and Proline Figure

In addition to synthesis of NO, urea, and ornithine, arginine is used for synthesis of creatine, which is an important constituent of skeletal muscle and neurons and acts as an energy source for these tissues. Furthermore, arginine may be catabolyzed to agmatine, which acts as a cell-signaling molecule. Arginine not only acts as an intermediate in the

Curcumin Inhibits Myocardial Infarction

Nirmala and Puvanakrishnan investigated the effect of curcumin on lysosomal hydrolases (h-glucuronidase, h-N-acetylglucosaminidase, cathep-sin B, cathepsin D, and acid phosphatase) in serum and heart after isopro-terenol (ISO)-induced MI (95). Rats treated with ISO (30 mg 100 g body weight) showed a significant increase in serum lysosomal hydrolase activities, which were found to decrease after curcumin treatment. ISO administration to rats resulted in decreased stability of the membranes, which was reflected by the lowered activity of cathepsin D in mitochondrial, lysosomal, and microsomal fractions. Curcumin treatment returned the activity levels almost to normal, showing that curcumin restored the normal function of the membrane. Histopathological studies of the infarcted rat heart also showed a decreased degree of necrosis after curcumin treatment. Nirmala and Puvanakrishnan also examined the effect of curcumin on the biochemical changes induced by ISO administration in rats (96)....

Marginal Compounds and Phytonutrients

In addition to the established vitamins, a number of organic compounds have clear metabolic functions they can be synthesized in the body, but it is possible that under some circumstances (as in premature infants and patients maintained on long-term total parenteral nutrition) endogenous synthesis may not be adequate to meet requirements. These compounds include biopterin (Section 10.4), carnitine (Section 14.1), choline (Section 14.2), creatine (Section 14.3), inositol (Section 14.4), molybdopterin (Section 10.5), taurine (Section 14.5), and ubiquinone (Section 14.6).

Role Of Acetaldehydeprotein Adducts And Free Radicals

The increase in malondialdehyde-acetaldehyde protein adducts supports previous suggestions that alcohol induces cardiac lipid peroxidation 83,84 concomitant with endogenous cardiac-derived acetaldehyde formation, possibly via alcohol dehydrogenase (ADH) or cytochrome P450 actions. However, although the activity of cardiac alcohol dehydrogenase is low, catalase may also generate acetaldehyde 85-88 , The importance of these studies relates to the observation that malondialdehyde-acetaldehyde adducts are cytotoxic, inducing the release ofTNF-alpha and up-regulating ICAM-1 in endothelial cells in vitro 89 , Reactive oxygen free radical species may play a prominent role in alcohol-induced heart muscle damage. Cardiac tissue from chronic alcohol misusers shows increased 'agepigments indicative of damage by reactive oxygen species 90 , Involvement of reactive oxygen species damage is also implicated by studies showing that in alcohol-fed rats, the resulting shift in fatty acid profile is...

Local Skin Reaction And Cutaneous Microcurrent Mechanism

Dry Skin Mechanism

Held under load in a relatively fixed position for prolonged periods, as with unbalanced exercise, then discomfort, soreness, or pain develops, with a peak of discomfort during the first day or two. Pain makes muscles sensitive to palpation it restricts their range of motion and sometimes causes slight swelling. In this type of injury, some disorganization of the striation of muscle fibers has been observed, and a lack of myofibrillar regeneration could persist as long as 10 days.13 Changes in blood chemistry profiles have been noticed, including increases in plasma levels of interleukin-1, acid-reactive substances, lactic dehydrogenase, serum creatine, phos-phokinase, aspartate aminotransferase, and serum glutamic oxaloacetic transaminase. Most of those enzymes are involved in muscle metabolism.

Heart Involvement in SLE

It is rare but possible for the heart muscle to become significantly inflamed in children with SLE. If myocarditis is present, there may be chest pain and there will be an increase in the blood level of creatine kinase (CK), an enzyme that is found in both heart muscle and other tissues the laboratory can determine whether the CK is coming from the heart, other muscles, the brain, or elsewhere. Myocarditis may cause abnormalities in the heart rhythm that will show up on an electrocardiogram (EKG). It may also interfere with the ability of the heart to pump blood, producing symptoms of poor heart output.

Effects Of Cordyceps On The Kidney

Blood creatine, urea, and urine N-acetyl-glucosaminidase were determined these clinical parameters demonstrated that the Cordyceps-treated group developed less prominent nephrotoxicity as compared with the placebo group. The longer the administration time, the more significant was the difference of tested clinical results between the two groups. Thus, these findings suggested that Cordyceps exerts a protective effect against cyclospo-rine-induced nephrotoxicity (52).

Glycine Serine and Threonine

Thought to possess anti-inflammatory properties, but to date these properties have only been demonstrated in the test tube. Furthermore, glycine can react with arginine and methionine to form creatine (see section on arginine). Finally, glycine, like taurine, is a conjugate for bile acids.

Cysteine Cystine Methionine and Taurine Figure

Methionine is converted to cysteine and its dipeptide cystine. In addition methionine is a precursor for creatine (see arginine). The potential for formation of disulfide bonds between its thiol (-SH) groups makes protein-bound cysteine important in the folding and structural assembly of proteins. Reduced cysteine thiol groups are found in protein (albumin), free cysteine, and in the principal intracellular anti-oxidant tripeptide glutathione (see glycine, glutamic acid) for which free cysteine is the synthesis rate-limiting constituent. Through the formation of disulfides (e.g., cystine, cysteinyl-glutathione, glu-tathione disulfide, mercaptalbumin) thiol-containing molecules can scavenge oxygen-derived free radicals. The ratio between oxidized and reduced thiol groups reflects the cellular redox state. Owing to its small pool size cysteine deficiencies rapidly occur during malnutrition. Arginine Creatine

Calcium Phosphate Interrelationships

Hormones, such as PTH and 1,25-dihydroxyvitamin D, on bone, the gut, and the kidneys. Adequate phosphorus and calcium intakes are needed not only for skeletal growth and maintenance but also for many cellular roles, such as energy production (i.e., adenosine triphosphate (ATP)). Phosphate ions are incorporated in many organic molecules, including phospholipids, creatine phosphate, nucleotides, nucleic acids, and ATP.

High Intensity Exercise and Strength Training

Metabolic In addition to the neuromuscular alterations that occur with high-intensity and strength training, several metabolic adaptations improve the ability of the muscle to resynthesize ATP from anaerobic sources. Intramuscular stores of the anaerobic energy intermediates, such as creatine phosphate (CP) and glycogen, increase after a period of supramaximal training. The activity of enzymes involved in anaerobic production of energy, such as creatine kinase and myokinase, is also increased.

Other Methods

There are many other methods used to measure body fat, including total body potassium, total body electrical conductivity, isotopic dilution, urinary creatine excretion, total body calcium, total body nitrogen, total plasma creatinine, computerized tomography, magnetic resonance imaging (MRI), ultrasound, neutron activation analysis, and dual photon absorpitometry. While some of these hi-tech methods may be incredibly accurate and useful in the laboratory, none of these methods are practical for your own personal use on a fat loss program.


A case report of anabolic steroid abuse (classified as hallucinogen abuse by the National Institute on Drug Abuse) utilized MR imaging to document a right basal ganglia ischemic infarction, in a young man with a 6 wk history of steroid abuse who presented with left hemiparesis (Akhter et al., 1994). A study in anesthetized rodents using long echo time gradient echo fMRI imaging found increased cerebral blood flow (rCBF) in the hippocampus, cortex, and olfactory bulb following ketamine administration, which implied a selective receptor-mediated effect of the drug on rCBF (Burdett et al., 1995). A case report of acute inflammatory CNS disease in association with methylenedioxymethamphetamine (MDMA) abuse was described (Bitsch et al., 1996). Low baseline 1H MRS choline (Cho) levels were found in a case report of a chronic MDMA abuser, and total creatine (Cr) levels were elevated in that subject 2 wk after an acute MDMA (0.5 mg kg) challenge (Grob et al., 1996).

Energy Production

Although the exact mechanism is unknown, much is known about the biochemistry of endogenous creatine. In skeletal muscle tissue, it is used for the production of phosphocreatine, an important form of high-energy phosphate. Phosphocreatine is broken down into phosphate and creatine during high intensity exercise lasting 1 5-30 seconds. During the process, energy is released and is used to regenerate ATP, the primary source of energy. Supplemental creatine Oral supplementation with creatine has been shown to increase phosphocreatine levels in muscles, and as such, has been described as 'fuelling up' natural energy stores. Increased creatine stores leads to faster regeneration of ATP, thereby making more energy immediately available to muscles. Theoretically, increased free creatine allows depleted stores to replenish more quickly, thus shortening recovery times during repeated bouts of intense exercise. Increased muscle creatine may also buffer the lactic acid produced during exercise,...


Creatine supplementation has displayed neuroprotective effects in several animal models of neurological disease, such as Huntington's disease, Parkinson's disease, or motor neurone disease (MND) (also known as amyotrophic lateral sclerosis) (Andreassen et al 2001, Dedeoglu et al 2003, Ferrante et al 2000, Wyss & Schulze 2002) and is currently being evaluated in early stage trials in Parkinson's disease and MND (Beal 2003). A number of theories of a possible mechanism for neuroprotection have been put forward. One theory proposes that creatine exerts antioxidant activity and mitochondrial stabilising effects, two mechanisms of benefit in neurodegenerative diseases, which are characterised by mitochondrial dysfunction and Creatine 331 oxidative damage (Shefner et al 2004).

Muscular Dystrophy

A number of muscle diseases are associated with a decrease in intracellular creatine concentration, which could theoretically contribute to muscle weakness and degeneration of muscle tissue (Wyss et al 1998). As a result, testing with creatine supplementation in a variety of muscle diseases has started. One double-blind, crossover study of 36 patients with various muscle diseases found that creatine supplementation over 8 weeks produced a mild but significant improvement in muscle strength and daily-life activities on Medical Research Council scales and the Neuromuscular Symptom Score (Walter et al 2000). A single-blind placebo-controlled trial of 21 volunteers with different neuromuscular disorders found that creatine supplementation (10 g daily for 5 days followed by 5 g daily for 5-7 days) produced significant improvements in body weight, handgrip, dorsiflexion, and knee extensor strength (Tarnopolsky et al 1997).


Patients diagnosed with CFS have been the focus of some studies of muscle fatigue, which do not consistently show that the problem resides in the periphery, that is, the muscle or its innervation (Wessely et al. 1998). In one study, increased 2'-5'A synthetase, and RNAase L activity, led to depleted cellular ATP which was thought to be 'a pivotal lesion responsible for severe fatigue, cognitive difficulties, or other disturbances' (Forsyth et al. 1999). However, other investigators have found impaired synthesis of ATP and defective muscle energy metabolism, along with impaired voluntary activation of skeletal muscle during sustained intense exercise, in a proportion of patients with CFS (Lane et al. 1998). The latter finding is suggestive of the presence of a central component of fatigue (Kent-Braun et al. 1993). In non-dialysed patients with chronic renal failure who often complain of muscle weakness and fatigue after minor physical activity and may suffer from myopathy related to...


(brain) of fatigue and those operating at the level of the neuromuscular system. Research tools such as assessment of physical activity using actigraphy and concomitant measurement of metabolic activity (for example, ATP, creatine phosphate, and lactate levels) in muscle tissue biopsy samples, or preferably in situ, using nuclear magnetic resonance (NMR) and related techniques, could be used to further evaluate this hypothesis. Further indirect support would come from therapeutic trials of agents enhancing the formation of ATP, such at NAD (Forsyth et al. 1999).

MR Spectroscopy

Changes to osmotic stress and neuronal swelling (Christensen et al., 1997). Similar cocaine-induced increases in basal ganglia and thalamic NAA total creatine ratios (NAA Cr) have been reported in chronic cocaine users, although baseline NAA Cr ratios in the basal ganglia, frontal lobe, and thalamus in those subjects were lower than control levels (Li et al., 1996, 1998).

Chronic Effects

To abnormal synthesis or breakdown of myelin phospholipids (MacKay et al., 1993). A proton spectroscopy (1H MRS) study of chronic cocaine users evaluated after a median 12 mo of abstinence revealed elevated white matter total creatine (Cr) and myoinositol (Ino) levels (Chang et al., 1997a). Several correlations between 1H MRS metabolites and drug use demographics were found, including negative correlations between N-acetylaspartate Cr (NAA Cr) ratios and both frequency and duration of cocaine use (Chang et al., 1997a). Another MRS study of chronic cocaine users revealed abnormally low NAA Cr ratios in basal ganglia and frontal cortex (Li et al., 1996).


Synthesis of S-adenosyl-L-methionine (SAMe) A THF derivative is critical for the regeneration of methionine from homocysteine. The methyl group donated in this process is taken up by SAMe, which provides it with the ability to become a carbon donor in multiple transmethylation reactions throughout the body including the synthesis of adrenaline, melatonin and creatine (Hendler & Rorvik 2001). Amino acid metabolism Folate is involved in the synthesis of some of the nonessential amino acids such as serine and glycine. It is also required for the conversion of histidine into glutamate (Gropper et al 2005).

Specific Analytes

Folin was the first to use the Duboscq colorimeter in a clinical chemistry procedure. He published methods for urine creatinine and creatine in 1904 based on the colorimetric alkaline picric acid reaction (5,6). Prior to the Duboscq, colorimetric clinical chemistry assays were read by holding the test tubes with the unknowns up against a white background and color matching them against tubes containing standards or up against colored glass filters previously matched against liquid standards for that assay. The Duboscq colorimeter replaced this with a quantitative measure of the difference in color intensity between samples. In addition, because of its optical design, it improved the ability to distinguish between weak differences in intensity. (7) Folin, O. (1914) On the determination of creatinine and creatine in blood, milk and tissues. Journal of Biological Chemistry. 17(4) 475-481.


Both a crude and a standardised extract (G11 5) of ginseng varying in saponin concentrations have been found to protect against muscle fibre injury and inflammation after eccentric muscle contractions in rats on a treadmill. The oral ginseng extracts significantly reduced plasma creatine kinase levels by about 25 and lipid peroxidation by 1 5 . Certain markers of inflammation were also significantly reduced (Cabral de Oliveira et al 2001). In a later study, pretreatment with ginseng extract (3, 10, 100 or 500 mg kg) administered orally for 3 months to male Wistar rats resulted in a 74 decrease in lipid peroxidation caused by eccentric exercise (Voces et al

Designer Foods

Sports nutrition is another established arena for designer foods. Specific nutritional measures and dietary interventions have been devised to support athletic performance and recuperation. Oral rehy-dration products for athletes were one of the first categories of functional foods for which scientific evidence of benefit was obtained. Oral rehydration solutions must permit rapid gastric emptying and enteral absorption, improved fluid retention, and thermal regulation, to enhance physical performance and delay fatigue. Carbohydrates with relatively high glycemic index combined with whey protein concentrates or other sources of branched chain amino acids have been shown to enhance recovery of athletes. Caffeine, creatine, ribose, citrulline, L-carnitine, and branched chain amino acids have each been shown to improve exercise performance or diminish postexercise fatigue. Whether combinations of these ingredients, blended into foods or beverages, will perform better than the individual...


We found that acute moderate alcohol exposure directly protected cardiac myocytes from ischemia-induced damage 32 , Under normoxic conditions over 3 hours of incubation, 10 of cells demonstrated osmotic fragility, indicating that isolated myocytes remained healthy. Under simulated ischemic conditions over 3 hours of incubation, 75 of myocytes demonstrated osmotic fragility. Ten minute exposure of myocytes to 50 mM ethanol before, but not during, simulated ischemia reduced cell damage by 35 . Exposure of cardiac myocytes tojust 10 mM ethanol throughout simulated ischemia reduced cell damage by 56 . Furthermore, 20 minute Langendorff perfusion of isolated rat heart with 10 mM ethanol reduced creatine kinase release after 45 minutes of ischemia and 30 minutes of reperfusion by 70 . Therefore, brief exposure to physiological levels of ethanol induced powerful


L-Arginine is incorporated into tissue proteins, and is required for the synthesis of other amino acids, polyamines, and creatine, as well as for the detoxification of ammonia via the urea cycle (Rodwell, 1990). It is a dispensable glycogenic amino acid, synthesized in adequate amounts from the urea cycle intermediate ornithine. Ornithine, in turn, can be synthesized from proline and possibly from glutamate (Brunton et al., 1999). However, in children with congenital defects of argininosuccinic acid synthetase or argininosuccinase, both urea cycle enzymes, arginine is an indispensable amino acid with daily supplementation required (Brusilow and Horwich, 1989). Based on intake distribution data from the 19881994 NHANES III, mean daily intakes for all life stage and gender groups of arginine from food and supplements is approximately 4.2 g d (Appendix Table D-3). Men 51 through 70 years of age had the highest reported intake at the 99th percentile of 10.1 g d.

Clinical features

Mild muscular abnormalities have been described in several patients and consist mainly of muscular pain and cramps one patient was described with myopathy 6 . Creatine kinase (CK) levels are often found to be elevated (1,5-2,5 times normal) 23, 27 . Jones et al (2003) have shown that high levels of SAR1B mRNA expression occurs in tissues other than intestine 2 and, therefore, extra-intestinal clinical manifestations might occurr in AD CMRD. Silvain et al have described a cardiomyopathy in an adult and documented the accumulation of lipids in some muscle fibers 23 . Consequently, clinical evaluation and follow-up of these patients should include CK levels and cardiac examination.

Dietary Supplements

Athletes have not been well researched, and both safety and efficacy remain open to question for many of these products. Anyone seeking to improve health or performance would be better advised to ensure that they consume a sound diet that meets energy needs and contains a variety of foods. A recent development of concern to athletes is the finding of various prohibited doping agents in what should be legitimate sports nutrition products. Supplements for which there is good evidence of beneficial effects on performance include caffeine, creatine, and bicarbonate, but the risk of an inadvertent positive doping result must always be considered.

Heart Disease

The ability of PA to chelate iron and possibly reduce its free radical generating potential and subsequent lipid peroxidative damage Figure 14.3(C) may also protect the heart from ischemic and reperfusion injury 113 . Rao et al. 113 intravenously injected rats with saline or PA at levels up to 15 mg per 100 g of BW. Shortly after, the hearts were excised, and reperfusion injury was induced in vitro. The higher levels of injected PA resulted in lessened reperfusion injury by significantly reducing creatine kinase release, decreasing lipid peroxidation

Skeletal Muscle

Deficiencies of either alpha-tocopherol or selenium also occur naturally leading to, for example, white muscle disease which is seen in farm animals or horses where a combination of inadequate soil selenium is combined with poor dietary ATC 217-226 , Concomitant changes in this disorder include reduced plasma glutathione peroxidase activities and increased serum creatine kinase activities 221,227 ,


Function The essential amino acid L-methioninc (Met I is needed for the synthesis of proteins and is a precursor for L-cysteine (Cys). It has a special role as the precursor of S-adenosylmethionine (SAM). SAM provides methyl groups for the synthesis of adrenaline (epinephrine), creatine, melatonin, phosphatidylcholine, carnitine, and numerous other essential compounds and is the precursor of essential polyamincs. Met is also an energy fuel its complete oxidation requires thiamin, riboflavin, niacin, vitamin B6. vitamin B12. pantothenate, notin, lipoate, ubiquinone, iron, and magnesium disposal of the sulfur in Met requires molybdenum.


In their urine after a lot of physical activity, especially running. This is not significant either. However, people with nephrotic syndrome, a type of kidney damage, may constantly lose a lot of protein. This is determined by measuring the excretion of protein over a twenty-four-hour period or by comparing the ratio of protein to creatine in a urine specimen. Children with lupus may develop nephrotic syndrome. Children with amyloidosis, a rare complication of juvenile arthritis, often have protein in their urine and also may develop nephrotic syndrome.

Anabolic Agents

The most frequently and widely used category of ergogenic aids is those with supposed anabolic effects that is, they mimic the benefits of steroids (in a legal manner). Creatine is the most widely used supplement taken by both recreational and professional athletes. Creatine is synthesized in the kidneys, pancreas, and liver from amino acid precursors (methionine, arginine, and glycine), and is also found in meat, fish, and poultry. The ergogenic effect of supplemental creatine is attributed to its ability to increase tissue creatine levels beyond what the body can synthesize on its own, resulting in increased work capacity during intense activity requiring maximal or near maximal effort. It can also expedite the recovery rate following exercise. These benefits are most likely seen with a regimen of 20 to 25 grams of creatine over five to seven days, divided into four- or five-gram doses (this is called the loading phase). Creatine levels will fall to presupplementation levels six...


Using citrulline as an arginine-delivering substrate has been suggested, but has not been applied clinically. Ornithine is supplied as part of the ornithine-a-ketoglutarate molecule (see glutamine). Creatine is widely used by professional and recreational athletes as a nutritional supplement, although the ascribed performance-enhancing effects have not been proven.