One case study exists of a man with focal segmental glomerulosclerosis who experienced an accelerated rate of GFR decline during supplementation (5g thrice daily for loading, then a 2g maintenance for seven weeks) which was partially reversed upon supplement cessation. This was deemed strong circumstantial evidence, and the brand of supplement was not named.[616] Elsewhere, interstitial nephritis associated with creatine supplementation has been reported in a man, although symptoms arose four weeks after supplementation started with no evidence to support correlation.[617] Some studies involving athletes and various dietary supplements have attempted to draw a correlation with creatine and cases of rhabdomyolysis.[618][619][620][621] Finally, one study in a diabetic person ingesting both metformin and creatine resulting in metabolic acidosis has attempted to place causation on creatine, but it did not establish causation or circumstantial evidence.[622]
It's OK to be a little sore. Your muscles might feel achy or tired the day after a tough training session thanks to DOMS, or delayed onset muscle soreness. When you strength train you're causing microscopic damage to the tissue that will be repaired, that's how you build stronger lean muscle. Speaking of repair and recovery, though, rest days are important. "If you constantly break down muscle without a recovery period, you won’t give the muscle fibers a chance to repair and build back stronger,” explains Davis.
Bodybuilding became more popular in the 1950s and 1960s with the emergence of strength and gymnastics champions, and the simultaneous popularization of bodybuilding magazines, training principles, nutrition for bulking up and cutting down, the use of protein and other food supplements, and the opportunity to enter physique contests. The number of bodybuilding organizations grew, and most notably the International Federation of Bodybuilders (IFBB) was founded in 1946 by Canadian brothers Joe and Ben Weider. Other bodybuilding organizations included the Amateur Athletic Union (AAU), National Amateur Bodybuilding Association (NABBA), and the World Bodybuilding Guild (WBBG). Consequently, the male-dominated contests grew both in number and in size. Besides the many "Mr. XXX" (insert town, city, state, or region) championships, the most prestigious titles[according to whom?] were Mr. America, Mr. World, Mr. Universe, Mr. Galaxy, and ultimately Mr. Olympia, which was started in 1965 by the IFBB and is now considered the most important bodybuilding competition in the world.

There is a great amount of research published on creatine supplementation; protocols of administration, forms of creatine, as well as potential side effects. Despite this, the mechanisms by which creatine acts in the human body to improve physical and cognitive performance are still not clear. The main objectives of this review are to analyze the more recent findings on the effects and mechanisms of creatine supplementation in sports and health. As a secondary purpose, we will analyze the most recommended protocols of ingestion and its potential side effects.
Some of these medications that can harm the kidneys include cyclosporine (Neoral, Sandimmune); aminoglycosides including amikacin (Amikin), gentamicin (Garamycin, Gentak, others), and tobramycin (Nebcin, others); nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen (Advil, Motrin, Nuprin, others), indomethacin (Indocin), naproxen (Aleve, Anaprox, Naprelan, Naprosyn), piroxicam (Feldene); and numerous others.

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]

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]


But one question has repeatedly popped up: When is the best time to take creatine? Recent research has suggested that there might be an ideal time. That’s when I decided to speak with the supplement experts at Examine.com. For those of you who don’t know, they have created the world’s largest database of facts about supplements. No marketing BS. Just a bunch of Ph.D’s, PharmD’s, and biomedical researchers who are obsessed with sharing the truth. Their Supplement Guide is the best thing written about supplements since…well…ever. If you’ve ever had a question it’s pack with research and fact-based information to help you make healthier supplement choices.
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]  
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