The genealogy of lifting can be traced back to the beginning of recorded history[1] where humanity's fascination with physical abilities can be found among numerous ancient writings. In many prehistoric tribes, they would have a big rock they would try to lift, and the first one to lift it would inscribe their name into the stone. Such rocks have been found in Greek and Scottish castles.[2] Progressive resistance training dates back at least to Ancient Greece, when legend has it that wrestler Milo of Croton trained by carrying a newborn calf on his back every day until it was fully grown. Another Greek, the physician Galen, described strength training exercises using the halteres (an early form of dumbbell) in the 2nd century.
^ The effect of HMB on skeletal muscle damage has been assessed in studies using four different biomarkers of muscle damage or protein breakdown: serum creatine kinase, serum lactate dehydrogenase, urinary urea nitrogen, and urinary 3-methylhistidine.[38][41][42] When exercise intensity and volume are sufficient to cause skeletal muscle damage, such as during long-distance running or progressive overload, HMB supplementation has been demonstrated to attenuate the rise in these biomarkers by 20–60%.[38][42]
Besides the high-quality protein content of casein/whey, the newer formulations have little or no lactose (i.e., milk sugar), which some people have negative reactions to. The native milk proteins also provide a host of smaller proteins called peptides, many of which, such as lactoferrin, have vital health benefits. The rich cysteine content of whey acts as a precursor of glutathione, a primary endogenous antioxidant and liver detoxifier in the body.
Legion’s Recharge is a good pick for muscle growth. Besides the creatine itself, it contains a hefty 2.1 grams of l-carnitine l-tartrate, which has solid links with improving muscle repair in addition to increasing focus during workouts. It’s also delicious, naturally sweetened, and it contains ingredients that may improve insulin sensitivity and help the body to better utilize carbs for recovery.
Creatine is classified as a "dietary supplement" under the 1994 Dietary Supplement Health and Education Act and is available without a prescription. Creatine is not subjected to FDA testing, and the purity and hygienic condition of commercial creatine products may be questionable [21]. A 1998 FDA report lists 32 adverse creatine-associated events that had been reported to FDA. These include seizure, vomiting, diarrhea, anxiety, myopathy, cardiac arrhythmia, deep vein thromboses and death. However, there is no certainty that a reported adverse event can be attributed to a particular product [22]. A recent survey of 28 male baseball players and 24 male football players, ages 18 to 23, found that 16 (31%) experienced diarrhea, 13 (25%) experienced muscle cramps, 7 (13%) reported unwanted weight gain, 7 (13%) reported dehydration, and 12 reported various other adverse effects [23].
Hartman, J. W., Tang, J. E., Wilkinson, S. B., Tarnopolsky, M. A., Lawrence, R. L., Fullerton, A. V., & Phillips, S. M. (2007). Consumption of fat-free fluid milk after resistance exercise promotes greater lean mass accretion than does consumption of soy or carbohydrate in young, novice, male weightlifters. The American Journal of Clinical Nutrition, 86(2), 373-381.
As mentioned, protein is essential for building muscle. If you are unable to consume the recommended amount of protein through diet alone, add protein powder for building muscle as a supplement. This applies to nearly anyone hoping to gain muscle mass since it’s not easy to pack in nearly 100 grams of protein a day through chicken, eggs and legumes alone.

However, a much more accurate determination of how much fluid is necessary can be made by performing appropriate weight measurements before and after a typical exercise session, to determine how much fluid is lost during the workout. The greatest source of fluid loss during exercise is through perspiration, but as long as your fluid intake is roughly equivalent to your rate of perspiration, hydration levels will be maintained.[14]
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]
This is why I never understand why girls who don’t want to “get bulky” are told by trainers to do 3 sets of 10-12 (or 5 sets of 1,000 reps of bicep curls with a 1 lb pink dumbbell). While it’s difficult for women to gain any sort of size lifting in ANY rep range, if we were trying to gain muscle size, that’s EXACTLY what we would want to do (as it would be causing sarcoplasmic hypertrophy).

Heath suggests incorporating dropsets into your training routine by immediately decreasing the weight and repping out again to failure. “Dropsets overload the muscle with shorter rest periods and increasing volume which you need to grow,” says Heath. “That overload improves your body’s abilities to utilize more nutrients, natural growth hormone, and natural testosterone into those areas and makes the supplements you take more effective.” Heath’s favorite way to do dropsets is on a pin-loaded machine since it’s faster to switch weights.
In the modern bodybuilding industry, the term "professional" generally means a bodybuilder who has won qualifying competitions as an amateur and has earned a "pro card" from their respective organization. Professionals earn the right to compete in competitions that include monetary prizes. A pro card also prohibits the athlete from competing in federations other than the one from which they have received the pro card.[12] Depending on the level of success, these bodybuilders may receive monetary compensation from sponsors, much like athletes in other sports.
When it comes to finding the right meal plan, you have to start somewhere. Start with writing down what you eat in a food diary, calculate the calories you’re consuming daily (ex: 3,000 without protein shakes), and break those up into six meals (ex: 500 calories each), says Heath. Then, choose a macronutrient ratio. For example, the 40% protein, 40% carbs, 20% fat ratio is what Heath used to get bigger when he first started bodybuilding. “Buy a food scale, learn how to use it, and you may even have to learn to use the metric system, like grams instead of ounces,” Heath says. “You need to train your body to process food quickly, so eat every three hours.”
When it comes to building lean muscle, size bodybuilders are king. That’s their ultimate goal. Sure, Crossfit, powerlifting and all the other modalities will build muscle, but that’s not their focus. They want performance and any muscle they build is a side effect. Not so with bodybuilding where muscle size and shape are the priorities. Learning how to build muscle for the sake of building muscle has some benefits to the performance athlete. It allows for ais less injury prone. Its also a fact that bigger muscle contract harder regardless of technique or form, so it’s a good strategy to throw in some bodybuilder muscle building sessions here and there to give yourself stronger muscles to then train for performance. Build the muscle bigger, then train it to perform better.
The general sentiment among nutrition experts is that creatine monohydrate is, for most people, the best bet. It’s the cheapest form and more importantly, it’s the most well-researched. Hundreds of studies have been performed on creatine monohydrate and there’s no evidence of ill effects, whereas many of the more novel forms of creatine have one or sometimes no studies supporting them.
It has been argued that purposely overtraining for a brief period can be beneficial. One article published by Muscle & Fitness magazine stated that you can "Overtrain for Big Gains". It suggested that if one is planning a restful holiday and does not wish to inhibit their bodybuilding lifestyle too much, they should overtrain before taking the holiday, so the body can recuperate and grow during the prolonged rest period. Overtraining can be used advantageously, as when a bodybuilder is purposely overtrained for a brief period of time to super compensate during a regeneration phase. These are known as "shock micro-cycles" and were a key training technique used by Soviet athletes.[53]

Contrast loading is the alternation of heavy and light loads. Considered as sets, the heavy load is performed at about 85-95% 1 repetition max; the light load should be considerably lighter at about 30-60% 1RM. Both sets should be performed fast with the lighter set being performed as fast as possible. The joints should not be locked as this inhibits muscle fibre recruitment and reduces the speed at which the exercise can be performed. The lighter set may be a loaded plyometric exercise such as loaded squat jumps or jumps with a trap bar.
Some people do have allergies to soy, or they have an intolerance to soy. If you notice certain symptoms (like a headache) after soy consumption, you may have an intolerance. Discovering your food intolerances/allergies would also be handled by a Dietitian. For the general population who are not allergic/intolerant to soy, however, soy-based products can be a part of a healthy diet. New research has shown that soy is not harmful as people fear. If soy gives you issues, you could always opt for whey protein, pea protein or other forms of vegetable protein. Have you seen our article on protein powders? Click here.
For example, a 2015 review published in the peer-reviewed journal Applied Physiology, Nutrition, and Metabolism suggests that, for maximal muscle growth, people consume 25 to 35 grams of protein at breakfast, lunch and dinner. You'll find that amount of protein in a chicken breast, a cup of Greek yogurt with slivered almonds or about a three-quarter block of tofu.

Dymatize Nutrition maximizes the benefits of protein in ISO-100 through its use of hydrolyzed 100% whey protein isolate. Designed to increase the absorption of protein, this fast-acting protein provides 25 grams of protein and 5.5 grams of BCAAs per serving, with no gluten or lactose. With a formula that aids in the instantaneous delivery of effective and advanced protein forms straight to the muscle, ISO-100 is able to repair and build muscle faster, resulting in the ability to reach fitness goals sooner rather than later. Keep Reading »
Three amino acids (glycine, arginine and methionine) and three enzymes (L-arginine:glycine amidinotransferase, guanidinoacetate methyltransferase and methionine adenosyltransferase) are required for creatine synthesis. The impact creatine synthesis has on glycine metabolism in adults is low, however the demand is more appreciable on the metabolism of arginine and methionine [11].
You've got your equipment ready, now it's time to choose about eight to 10 exercises, which comes out to about one exercise per muscle group. Use the list below to choose at least one exercise per muscle group to start. For the larger muscles, like the chest, back, and legs, you can usually do more than one exercise. These involve a variety of equipment, so you can choose based on what you have available.
After supplementation of creatine monohydrate (loading phase, followed by 19 weeks maintenance), creatine precursors are decreased by up to 50% (loading) or 30% (maintenance), which suggests a decrease in endogenous creatine synthesis during supplementation.[38] This appears to occur through creatine’s own positive feedback and suppression of the l-arginine:glycine amidinotransferase enzyme, the rate-limiting step in creatine synthesis, as levels of intermediates before this stage are typically elevated by up to 75%.[38]
You've got your equipment ready, now it's time to choose about eight to 10 exercises, which comes out to about one exercise per muscle group. Use the list below to choose at least one exercise per muscle group to start. For the larger muscles, like the chest, back, and legs, you can usually do more than one exercise. These involve a variety of equipment, so you can choose based on what you have available.
Creatine is thought to improve strength, increase lean muscle mass, and help the muscles recover more quickly during exercise. This muscular boost may help athletes achieve bursts of speed and energy, especially during short bouts of high-intensity activities such as weight lifting or sprinting. However, scientific research on creatine has been mixed. Although some studies have found that it does help improve performance during short periods of athletic activity, there is no evidence that creatine helps with endurance sports. Research also shows that not everyone's muscles respond to creatine; some people who use it see no benefit.

Using an ultra-pure and effective creatine formula, AI Sports' Micronized Creatine serves 5 grams of the purest creatine which can help the body to enhance the production of ATP and boost the growth as well as development of muscle. Along with promoting the increase of muscle mass, Micronized Creatine may also be able to build strength and improve performance while preventing the fatigue of muscle. Experience the enhancement that Micronized Creatine can provide to help level up your training sessions. Keep Reading »
Many trainees like to cycle between the two methods in order to prevent the body from adapting (maintaining a progressive overload), possibly emphasizing whichever method more suits their goals; typically, a bodybuilder will aim at sarcoplasmic hypertrophy most of the time but may change to a myofibrillar hypertrophy kind of training temporarily in order to move past a plateau. However, no real evidence has been provided to show that trainees ever reach this plateau, and rather was more of a hype created from "muscular confusion".[clarification needed][citation needed]
He pointed to data sets in Mayo Clinic Proceedings that found resistance training reduced the risk of developing metabolic syndrome or hypercholesterolemia. “If you build muscle, even if you’re not aerobically active, you burn more energy because you have more muscle. This also helps prevent obesity and provide long-term benefits on various health outcomes.”
There have also been concerns that creatine can cause kidney damage, and doctors warn that people with a history of kidney disease or conditions, such as diabetes, that increase the risk of kidney problems should steer clear of the supplement. Combining creatine with nephrotoxic drugs — drugs that might damage the kidneys — like nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (advil or motrin) and naproxen sodium (Aleve), should also be avoided, according to the U.S. Department of Health and Human Services. (1)
Peirano, R. I., Achterberg, V., Dusing, H. J., Akhiani, M., Koop, U., Jaspers, S., Kruger, A., Schwengler, H., Hamann, T., Wenck, H., Stab, F., Gallinat, S., and Blatt, T. Dermal penetration of creatine from a face-care formulation containing creatine, guarana and glycerol is linked to effective antiwrinkle and antisagging efficacy in male subjects. J.Cosmet.Dermatol. 2011;10:273-281. View abstract.

Why it made the list: Whey tops the list of mass-gain supplements because it's the most crucial for pushing protein synthesis. Whey is a milk protein that has a high level of branched-chain amino acids (BCAAs, No. 4 on our list). Bottom line: Whey takes the crown because it digests fast and gets to your muscles rapidly to start building muscle. Whey also contains peptides (small proteins) that increase blood flow to the muscles. This is why we always recommend consuming whey protein immediately after training.
Beast Creature could be another good option for female athletes. It’s tasty, it contains five types of creatine, and it contains ingredients that could improve fat loss by increasing insulin sensitivity. One potential bonus is that it also has 70 percent of your daily biotin, a nutrient often included in women’s multivitamins due its purported benefits for hair and nails.
In regard to bioenergetics, phosphorylated cyclocreatine appears to have less affinity for the creatine kinase enzyme than phosphorylated creatine in terms of donating the high energy phosphate group (about 160-fold less affinity) despite the process of receiving phosphorylation being similar.[104][105] When fed to chickens, phosphorylated cyclocreatine can accumulate up to 60mM in skeletal muscle,[106] which suggests a sequestering of phosphate groups before equilibrium is reached.[105] Cyclocreatine still has the capacity to donate phosphate, however, as beta-adrenergic stimulated skeletal muscle (which depletes ATP and glycogen) exhibits an attenuation of glycogen depletion (indicative of preservation of ATP) with phosphocreatine.[102]

In elite swimmers, the growth hormone response to sprints appears to be attenuated (39%) following creatine loading, although after a 3g maintenance phase (22-27 weeks), this attenuation was reduced to less than 5%.[404] Elsewhere in swimmers, resting growth hormone was unaffected by the loading phase,[397] suggesting that this is an exercise-exclusive effect.
Consult your physician and follow all safety instructions before beginning any exercise program or using any supplement or meal replacement product, especially if you have any unique medical conditions or needs. The contents on our website are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment.
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.

Yang, L., Calingasan, N. Y., Wille, E. J., Cormier, K., Smith, K., Ferrante, R. J., & Beal, M. F. (2009, June). Combination therapy with coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson's and Huntington's diseases [Abstract]. Journal of Neurochemistry. 109(5):1427-39. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/19476553
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]
Consult your physician and follow all safety instructions before beginning any exercise program or using any supplement or meal replacement product, especially if you have any unique medical conditions or needs. The contents on our website are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment.
In October 1994, the Dietary Supplement Health and Education Act (DSHEA) was signed into law in the USA. Under DSHEA, responsibility for determining the safety of the dietary supplements changed from government to the manufacturer and supplements no longer required approval from the U.S. Food and Drug Administration (FDA) before distributing product. Since that time manufacturers did not have to provide FDA with the evidence to substantiate safety or effectiveness unless a new dietary ingredient was added. It is widely believed that the 1994 DSHEA further consolidated the position of the supplement industry and lead to additional product sales.[6]

K. Aleisha Fetters, M.S., C.S.C.S., is a Chicago-based personal and online trainer. She has a graduate degree in health and science reporting from the Medill School of Journalism at Northwestern University and regularly contributes to Men's Health, Women's Health, USNews.com, TIME, and SHAPE. When she's not lifting something heavy, she's usually guzzling coffee and writing about the health benefits of doing so.
Naturo Nitro Creatine Chrome could be an interesting choice for women. It’s actually magnesium creatine chelate, a type of creatine that may help to improve performance without increasing water weight. We don’t have a lot of studies on it just yet, but the research we do have suggests it could potentially be a good choice for women who want to improve performance without experiencing the “bloat” of regular creatine.
I can’t predict what sort of results you’ll see in that first year, but it can be pretty epic if you attack it right! Muscle growth might happen slower than you want, but I expect something different will happen along the way – you’ll fall in love with this idea of building STRENGTH! In fact, getting hooked on progress, and strength training is one of the best things you can do for yourself.
If you’re not lifting super-heavy weights, doing high-intensity workouts, or eating a mainly vegan or vegetarian diet, your body probably makes as much creatine as it needs. “Creatine is naturally found in animal-based products,” says Bates, “so your body can make plenty of creatine as long as you have a balanced diet that includes animal-based products.” Protein sources like beef, chicken, pork, and fish help your body produce the creatine it needs — it varies depending on the source, but, in general, a 3-ounce serving of meat will have about 0.4 grams (g) of creatine, Bates says. (6)
Generally, you should consume about 20 grams of protein with some carbs shortly after a workout. During the post-workout anabolic window, you’ll also want to limit fats, which can slow the absorption of protein. While there is some recent research that suggests the window may actually extend up to several hours following exercise, there’s no harm in getting nutrients in early as long as you’re sticking to your overall caloric and macronutrient goals.

Creatine may preserve dopamine synthesis in the striatum of mice (while protecting against dopaminergic depletion) when fed to mice at 2% of the diet for one week prior to MPTP toxicity[230]. This is possibly secondary to increasing tyrosine hydroxylase activity, the rate-limiting step of dopamine biosynthesis.[210][235] Two percent creatine was as protective as 0.005% rofecoxib (a COX2 inhibitor), but the two were additive in their protective effects (highly synergistic in regard to DOPAC by normalizing it, but not synergistic in preserving HVA).[230]

You can't scroll through Instagram without clocking a mammoth cheat day feast, but are real-life bodybuilders consuming such a crazy amount of calories every couple of weeks? Not quite. When he’s dieting for a competition, Terry incorporates ‘re-feed days’ into his schedule. This means he eats the exact same food, but essentially doubles the portion sizes.
The important role of nutrition in building muscle and losing fat means bodybuilders may consume a wide variety of dietary supplements.[41] Various products are used in an attempt to augment muscle size, increase the rate of fat loss, improve joint health, increase natural testosterone production, enhance training performance and prevent potential nutrient deficiencies.

Macrophages are known to express creatine kinase[290] and take creatine up from a medium through a sodium dependent mechanism (likely the creatine transporter) in a saturable manner,[435] with a second component that requires there to be no concentration gradient to work against (likely passive diffusion) but this effect tends to only account for up to 10% of total uptake in the physiological range (20-60µM).[435] Supraphysiological range was not tested.


Beach muscles and Olympic lifts draw more attention. But the many little stabilizer muscles around your shoulders, hips, and midsection — collectively the core — provide a strong foundation. Challenging the stability and mobility of these key muscles with medicine balls, physioballs, mini-bands, and rotational movements (lifting, chopping) pays huge dividends. 

This muscle-building, power-enhancing supplement has an extremely high safety profile and a plethora of evidence to support its efficacy. Creatine supplementation works by increasing the availability of creatine and phosphocreatine (PCr) within the muscle, helping to maintain energy during high-intensity exercise such as weightlifting. Furthermore, increasing the availability of PCr may help speed up recovery between sets.
Extracellular creatine (creatine outside of a cell) appears to influence creatine uptake into a cell. It seems that prolonged and excessive levels of creatine actually suppress uptake (a form of negative regulation to prevent excessive influx).[180] In vitro studies in rat muscle cells have shown that including 1mM creatine into cell culture medium substantially reduces creatine uptake into cells. The inhibitory effect was partially negated by protein synthesis inhibitors, suggesting that high levels of creatine induce the expression of a protein that suppresses creatine transporter activity.[180] Similar findings were reported in a later study in cultured mouse myoblasts, which noted a 2.4-fold increase in intracellular creatine levels in the presence of the protein synthesis inhibitor cyclohexamide.[174]
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]
Creatine transport has been shown to increase when muscle creatine stores are depleted. This was only noted to occur in muscle with particular fiber types (soleus and red gastrocnemius), while other fiber types, such as white grastrocnemius, did not show any clear trend.[146] This indicates that transport in relation to total creatine levels varies across different muscle fiber types.
A thermogenic is a broad term for any supplement that the manufacturer claims will cause thermogenesis, resulting in increased body temperature, increased metabolic rate, and consequently an increased rate in the burning of body fat and weight loss. Until 2004 almost every product found in this supplement category comprised the "ECA stack": ephedrine, caffeine and aspirin. However, on February 6, 2004 the Food and Drug Administration (FDA) banned the sale of ephedra and its alkaloid, ephedrine, for use in weight loss formulas. Several manufacturers replaced the ephedra component of the "ECA" stack with bitter orange or citrus aurantium (containing synephrine) instead of the ephedrine.
Incubation of a β-cell with additional creatine (5-10mM), even at saturated concentrations of glucose, is able to further increase insulin secretion in response to glucose, specifically as the leucine metabolite 2-ketoisocaproic acid, potassium, and a potassium channel blocker were all ineffective.[494] This has been found to occur in rats given 2% of the diet as creatine[345] but has since failed in humans given 5g of creatine.[351]
Healthy sources of fat include: cold water oily fish (such as salmon, mackerel, and sardines), extra-virgin olive oil, peanuts (unsalted), avocado, pecans, almonds, hazelnuts, walnuts or flaxseed. Nuts (any sort, just make sure they are unsalted) are a great food to snack on if you're having trouble gaining weight, as they are not only high in calories, but they contain monounsaturated fats, a good source of protein, fibre and contain a number of essential minerals that are needed for health. For those not consuming any oily fish, you may want to consider taking a fish oil supplement, such as cod liver oil or flaxseeds.
Compound exercises work several muscle groups at once, and include movement around two or more joints. For example, in the leg press, movement occurs around the hip, knee and ankle joints. This exercise is primarily used to develop the quadriceps, but it also involves the hamstrings, glutes and calves. Compound exercises are generally similar to the ways that people naturally push, pull and lift objects, whereas isolation exercises often feel a little unnatural.
You see, there is only so much muscle that the human body is capable of building in a given period of time. So, if you supply your body with MORE calories than it’s actually capable of putting towards the process of building new muscle… it’s not going to magically lead to additional muscle being built. It’s just going to lead to additional fat being gained.
BulkSupplements.com Creatine is a solid bet for the best micronized creatine. It’s certified Good Manufacturing Practices and it’s produced in an allergen-free facility, something many brands can’t offer. The downside is that if you order smaller quantities, it’s a little more expensive, but once you order one kilogram or higher, it becomes just about cheapest creatine you’re likely to find.

Extracellular creatine (creatine outside of a cell) appears to influence creatine uptake into a cell. It seems that prolonged and excessive levels of creatine actually suppress uptake (a form of negative regulation to prevent excessive influx).[180] In vitro studies in rat muscle cells have shown that including 1mM creatine into cell culture medium substantially reduces creatine uptake into cells. The inhibitory effect was partially negated by protein synthesis inhibitors, suggesting that high levels of creatine induce the expression of a protein that suppresses creatine transporter activity.[180] Similar findings were reported in a later study in cultured mouse myoblasts, which noted a 2.4-fold increase in intracellular creatine levels in the presence of the protein synthesis inhibitor cyclohexamide.[174]
In isolated striatal cells (expressing creatine kinase), seven day incubation of 5mM creatine (maximal effective dose) appears to increase the density of GABAergic neurons and DARPP-32 (biomarker for spiny neurons[225]) with only a minor overall trend for all cells[226] and showed increased GABA uptake into these cells, as well as providing protection against oxygen and glucose deprivation.[226]
Key point: Past a certain number of sets, the marginal increases in protein synthesis NO LONGER outweigh the cost of doing more sets. If 8 sets of chest exercises produce 95% of possible muscle protein synthesis… then it makes very little sense to do ANOTHER 10 sets (like most chest workouts) to try and inch out the final 5% of stimulation. Those extra 10 sets are simply damaging your muscle unnecessarily and impairing your ability to recover.
The failure of creatine to improve physical performance in these conditions is thought to be related to the myopathies in general, which are known to result in less phosphocreatine in skeletal muscle,[568] associated with reduced expression of the creatine transporter.[569] As creatine has once been noted to not accumulate in the skeletal muscle of people with DM1 given supplementation,[566] it is thought that the subjects did not respond to therapy.

Taking high doses of creatine might harm the kidneys. Some medications can also harm the kidneys. Taking creatine with medications that can harm the kidneys might increase the chance of kidney damage.

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.

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