If you’re looking to put on extra muscle mass and build strength, there are a few things that need to occur. The first of these, even though it may seem obvious, is that you will need to have an exercise routine. To stimulate maximum muscle growth, you’ll need to challenge yourself in the gym, forcing your muscles to adapt to heavier workloads by increasing in size and strength.
Studies of so-called "smart drugs" have also been taken out of context. Some "smart" nutrients, available over the counter, are marketed as a way to "increase mental focus and concentration during training." The problem is that the studies they're based upon involved either animals or people with brain pathology. In normal people the effects of smart drugs remain unproven, except anecdotally.
Include cardio training. Good cardiovascular health improves blood flow, a requirement for muscle growth. Doing cardio also improves your cardiovascular fitness, which allows you to use your muscle gains for various sports and activities. The standard recommendation is 150 minutes of moderate cardio each week, or 75 minutes of vigorous cardio, or an equivalent combination of the two. A good place to start would be doing 30-60 minutes of cardiovascular activity every other day or 3 times a week. Examples of cardio include running, biking, swimming, and any sport that involves constant movement.

Competitive and professional bodybuilders, however, can often build up to two to three pounds of muscle per month during dedicated bulking periods. "But they are living and breathing muscle growth. They aren't just in and out of the gym like most people," Simpson says, noting that under extreme conditions, hyperplasia, or the growth in the number of muscle cells in a given muscle tissue, may actually occur, further adding to muscle growth results.


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.
So it was popular then, but is it effective now? Just because something is popular doesn’t mean it works. In the case of creatine supplementation, however, you can be confident that increased muscle strength and less fatigue is possible. All thanks to a critical chemical reaction taking place in your muscle cells. Read on and learn how creatine works and why it lives up to that nostalgic ‘90s hype.
Liquid creatine has been shown to be less effective than creatine monohydrate.[69] This reduced effect is due to the passive breakdown of creatine over a period of days into creatinine, which occurs when it is suspended in solution.[70] This breakdown is not an issue for at-home use when creatine is added to shakes, but it is a concern from a manufacturing perspective in regard to shelf-life before use.

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A push–pull workout is a method of arranging a weight training routine so that exercises alternate between push motions and pull motions.[28] A push–pull superset is two complementary segments (one pull/one push) done back-to-back. An example is bench press (push) / bent-over row (pull). Another push–pull technique is to arrange workout routines so that one day involves only push (usually chest, shoulders and triceps) exercises, and an alternate day only pull (usually back and biceps) exercises so the body can get adequate rest.[29]

There's good news, though: These temporary muscle pumps are critical to improving muscle hypertrophy, or muscle growth, according to 2014 research in the Strength and Conditioning Journal. So you can think of your weight-room pump as a preview of the muscle results that are to come. Speaking of which, here's an expert-endorsed timeline to reach your muscle-building goals.


The basic principles of weight training are essentially identical to those of strength training, and involve a manipulation of the number of repetitions (reps), sets, tempo, exercise types, and weight moved to cause desired increases in strength, endurance, and size. The specific combinations of reps, sets, exercises, and weights depends on the aims of the individual performing the exercise.
“There is a lot of mixed research on creatine’s ability to improve muscle strength,” the government website says. “However, analyses of this research show that creatine seems to modestly improve upper body strength and lower body strength in both younger and older adults.” Creatine has also been shown to improve athletes’ performance in rowing, soccer, and jumping height.
Nephrectomized rats may have significantly reduced creatine synthesis rates[509] via impairment of methylation (the GAMT enzyme)[510] although creatine reuptake from the urine seems unimpaired.[511] Supplemental creatine in a rat model of 2/3rds nephrectomy (2% creatine in the diet) does not appear to negatively influence kidney function as assessed by the serum biomarkers of cystatin C and urinary protein or creatinine clearance rates.[512] Elsewhere, 2% creatine in the diet in rats for two weeks again failed to show negative effects on kidney function, but showed benefit in reducing homocysteine in late-stage uremic rats.[312] While there is not much human evidence for the rat nephrectomy model, a lone case study in a man with a single kidney failed to find an impairing effect of creatine (20g daily for five days and 5g for another month) in conjunction with a high protein diet.[513]
There’s no need to go overboard on creatine intake, though, in search of crazy muscle growth: “The maximum amount of creatine that you can hold depends on the amount of muscle mass you have,” explains Bates. “So if you have more muscle, then your body can store more creatine. In general, the muscle can hold about 2 to 3 g of creatine per kilogram of muscle mass. So the amount of creatine you use will depend on the amount of muscle mass you have.” (7)

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Beta-alanine is a naturally occurring non-essential amino acid that comes into the body through foods that are rich in protein. The performance-enhancing aspect of beta-alanine (BA) is due to its ability to increase intra-muscular levels of carnosine. Increasing beta-alanine through supplementation may raise carnosine levels by over 60 percent in as quickly as four weeks.[6]
Weight gain might be the most common side effect. “Creatine can cause your body to hold on to water by pulling fluid into your cells via osmosis,” says Bates. “It doesn't necessarily cause you to gain weight as fat, but it can increase edema, or water weight.” Also, muscle is denser than fat, so in some cases building muscle can increase body weight overall (even if you’re simultaneously burning fat).
A quantitative, comprehensive scientific summary and view of knowledge up to 2007 on the effects of creatine supplementation in athletes and active people was published in a 100 citation review position paper by the International Society of Sports Nutrition[5]. More recent literature has provided greater insight into the anabolic/performance enhancing mechanisms of creatine supplementation [15,25] suggesting that these effects may be due to satellite cell proliferation, myogenic transcription factors and insulin-like growth factor-1 signalling [16]. Saremi et al [26] reported a change in myogenic transcription factors when creatine supplementation and resistance training are combined in young healthy males. It was found that serum levels of myostatin, a muscle growth inhibitor, were decreased in the creatine group.
Safety. Excess quantities of antioxidants may produce a ‘pro-oxidant’ effect, which is the opposite of what you would take these supplements for. The Australian Institute of Sport recommends that antioxidant vitamin supplements only be taken for a period of a few weeks while the body adjusts to stressful circumstances. Excess vitamin C may promote excess iron absorption, which may not be healthy for everyone. 

^ Burd, Nicholas A.; Yang, Yifan; Moore, Daniel R.; Tang, Jason E.; Tarnopolsky, Mark A.; Phillips, Stuart M. (2012). "Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. Micellar casein at rest and after resistance exercise in elderly men". British Journal of Nutrition. 108 (6): 958–62. doi:10.1017/S0007114511006271. PMID 22289570.
There's good news, though: These temporary muscle pumps are critical to improving muscle hypertrophy, or muscle growth, according to 2014 research in the Strength and Conditioning Journal. So you can think of your weight-room pump as a preview of the muscle results that are to come. Speaking of which, here's an expert-endorsed timeline to reach your muscle-building goals.
Weight training also requires the use of 'good form', performing the movements with the appropriate muscle group, and not transferring the weight to different body parts in order to move greater weight (called 'cheating'). Failure to use good form during a training set can result in injury or a failure to meet training goals; since the desired muscle group is not challenged sufficiently, the threshold of overload is never reached and the muscle does not gain in strength. At a particularly advanced level; however, "cheating" can be used to break through strength plateaus and encourage neurological and muscular adaptation.
Though weight training can stimulate the cardiovascular system, many exercise physiologists, based on their observation of maximal oxygen uptake, argue that aerobics training is a better cardiovascular stimulus. Central catheter monitoring during resistance training reveals increased cardiac output, suggesting that strength training shows potential for cardiovascular exercise. However, a 2007 meta-analysis found that, though aerobic training is an effective therapy for heart failure patients, combined aerobic and strength training is ineffective; "the favorable antiremodeling role of aerobic exercise was not confirmed when this mode of exercise was combined with strength training".[36]
The high levels of muscle growth and repair achieved by bodybuilders require a specialized diet. Generally speaking, bodybuilders require more calories than the average person of the same weight to provide the protein and energy requirements needed to support their training and increase muscle mass. In preparation of a contest, a sub-maintenance level of food energy is combined with cardiovascular exercise to lose body fat. Proteins, carbohydrates and fats are the three major macronutrients that the human body needs in order to build muscle.[24] The ratios of calories from carbohydrates, proteins, and fats vary depending on the goals of the bodybuilder.[25]
Most people require around 20 calories per pound (or 44 kcal / kg) of bodyweight to gain muscle mass. Using a 180-pound (82kg) male as an example, the required daily calorie intake is 3600 calories (20 kcal x 180 lb = 3600 kcal). When it comes to gaining weight, it is likely that you may put on a few pounds of fat along the way, but if you do find your body fat increasing, either increase the amount of aerobic exercise (moderate intensity) you are doing or slightly reduce the total number of calories you are consuming. Remember you can’t force feed muscle gain!
Bodybuilders also understand how to diet. This is perhaps the most important aspect other athletes can learn from. I can’t think of any athlete that comes close to bodybuilders who know how to build massive amounts of muscle and then can diet with the type of precision that gets them absolutely shredded on a specific date. Most resistance training sports use weight classes to compete. It doesn’t take a rocket scientist to see that shedding body fat without losing muscle can be a major advantage. Competing at a lower weight class because you are leaner while maintaining strength and performance is a very valuable and effective strategy. Diet to build LEAN muscle to keep weight low for a competitive advantage.

Different exercises will require different weights, but there are some markers that can help guide you towards the right resistance, whether you're using dumbbells, kettlebells, or a barbell. Go for a weight that feel heavy enough to challenge you, but not so heavy that you sacrifice your form. For example, if you're doing 15 reps, you should feel pretty fatigued by the time you hit rep 15. If you can breeze through all your reps, though, that's a sign you should up the weight.

This is another thing I am very tired of hearing. 'No matter what I do or what I eat, I can't gain weight'. I have heard this countless times and I am here to tell you that you are dead wrong. That's OK, because I actually said the same thing until I realized the truth. Most people think they are eating a lot and you just may be. But no matter what you are eating, if you are not gaining, you are not eating enough. Most times, you should re-evaluate your diet as well and focus on more calorie dense foods. But you need to eat more if you are not gaining.
Naturally produced in the kidneys, pancreas and liver, creatine is transported to muscle tissue where it is transformed into creatine phosphate, from which the energy molecule ATP is produced to regenerate the muscles' ability to contract and generate power during short-burst (anaerobic) activity. This translates to more productive workouts and faster muscle growth.

I’m going to cover this in detail in a bit, but for right now, just know this: it’s VERY possible (and common) to gain weight fast in the hopes of gaining muscle fast. The problem, however, is that the majority of the “weight” a person in this scenario will end up gaining will be body fat rather than muscle mass. This is something that needs to be avoided at all costs, and I’ll show you how a little later.
Every gym has a guy shaped like a lightbulb. He's the one who neglects his lower body. If you don't want to be that guy, work your major leg muscles on the leg press machine. Place your feet on the plate with knees bent at 90 degrees. Grasp the handles and slowly push the plate out until your knees are straight but not locked. Pause and slowly return to the starting spot.
If you're using a resistance band, keep in mind that one band might not cut it for your entire body. Different muscles have different strengths, so you may want to buy two different resistance bands in different thickness, which determines how difficult they'll be to use. In general, if you're able to complete 8 reps of an exercise using a band, you'll want to select another that provides a greater amount of resistance. 
Previous investigations have shown that a single dose of CM (8 grams) increased the number of repetitions performed during an upper-body resistance training protocol and reduced soreness at 24 and 48 hours post-exercise (compared to a placebo).7 Recently, researchers from Mississippi State University found that a single dose of CM (8 grams) significantly increased the number of lower-body repetitions compared to a placebo group.[8]
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] 
The incidence of liver damage from herbal and dietary supplements is about 16–20% of all supplement products causing injury, with the occurrence growing globally over the early 21st century.[2] The most common liver injuries from weight loss and bodybuilding supplements involve hepatocellular damage with resulting jaundice, and the most common supplement ingredients attributed to these injuries are catechins from green tea, anabolic steroids, and the herbal extract, aegeline.[2]
Do you know what happens when a person attempts to build muscle faster than they legitimately can? They fail, and then they wonder why it’s not working as quickly as they thought it would. From there, they’ll jump from workout to workout, diet to diet and useless supplement to useless supplement in the hopes of finally finding the missing link that will make it happen. But they’re never going to find it. They’ll just keep wasting their time, effort and money searching for something that doesn’t exist.
A: Eat more frequently, drink less liquids while eating (they compete for stomach volume along with food), eat from larger plates and bowls, add lime or lemon juice to your water with meals (can help to increase production of hydrochloric acid that breaks down food), and consume more liquid calories (especially around the workout if appetite is suffering the rest of the day).
Athletic performance. Creatine seems to help improve rowing performance, jumping height, and soccer performance in athletes. But the effect of creatine on sprinting, cycling, or swimming performance varies. The mixed results may relate to the small sizes of the studies, the differences in creatine doses, and differences in test used to measure performance. Creatine does not seem to improve serving ability in tennis players.
In addition to ALL of the above, strength training is fun! Whether you are looking for the most effective 20-30 minute workout (to stay fit and look great naked), or are looking for a competitive sport that you can really get into, strength training can help you meet your goals. It’s easy and fun to see progress as you strength train, almost like leveling up. And if you’re looking to improve in other areas (a sport, traditional cardio, or an activity like rock climbing), strength training is an easy choice!

It is known that intracellular energy depletion (assessed by a depletion of ATP) stimulates AMPK activity in order to normalize the AMP:ATP ratio,[333][334] and when activated AMPK (active in states of low cellular energy[335] and colocalizes with creatine kinase in muscle tissue[336]) appears to inhibit creatine kinase via phosphorylation (preserving phosphocreatine stores but attenuating the rate that creatine buffers ATP). While phosphocreatine technically inhibits AMPK, this does not occur in the presence of creatine at a 2:1 ratio.[334] It seems that if the ratio of phosphocreatine:creatine increases (indicative of excess cellular energy status) that AMPK activity is then attenuated, since when a cell is in a high energy status, there is less AMP to directly activate AMPK.[334][336][337]

Of course, cardio is an important part of fitness too, but the benefits of strength training are major. Strength training helps build muscle, and lean muscle is better at burning calories when the body is at rest, which is important whether you're trying to lose weight or maintain it. It also helps strengthens joints and bones, avoid injury, improve your muscular endurance, and will help you give it your all during your other workouts, whether that means setting a new PR if you're a runner or pushing (and pulling) a little harder with your legs during your favorite indoor cycling class.


Carducci, C., Birarelli, M., Leuzzi, V., Carducci, C., Battini, R., Cioni, G., and Antonozzi, I. Guanidinoacetate and creatine plus creatinine assessment in physiologic fluids: an effective diagnostic tool for the biochemical diagnosis of arginine:glycine amidinotransferase and guanidinoacetate methyltransferase deficiencies. Clin Chem 2002;48(10):1772-1778. View abstract.
There you have it — our five favorite creatine products on the market. But when you’ve tried as many creatines as we have, there were a lot of others that we loved but didn’t make the very top of our list for the previous categories. That’s why we’ve also come up with a list of the best creatines for men, best creatines for women, best creatines for muscle growth, for bulking, for the brain, and the best micronized creatine. Keep reading for our favorite picks!

Several review studies assessing the safety of creatine supplementation tend to make note of increases in formaldehyde and possible carcinogenic results.[451][452] Specifically, creatine is metabolized into an intermediate called methylamine, which can be converted to formaldehyde by the SSAO enzyme.[453] An increase in urinary formaldehyde has been noted in youth given 21g of creatine for one week, during which both methylamine (820% increase) and formaldehyde (350%) were increased, relative to control.[454] However, a more prolonged study using 300mg/kg (loading dose of around 20g) in adults for ten weeks failed to replicate these effects.[455]
It is regularly reported that creatine supplementation, when combined with heavy resistance training leads to enhanced physical performance, fat free mass, and muscle morphology [18-22]. A 2003 meta analysis [8] showed individuals ingesting creatine, combined with resistance training, obtain on average +8% and +14% more performance on maximum (1RM) or endurance strength (maximal repetitions at a given percent of 1RM) respectively than the placebo groups. However, contradicting studies have reported no effects of creatine supplementation on strength performance. Jakobi et al [23] found no effects of a short term creatine loading protocol upon isometric elbow flexion force, muscle activation, and recovery process. However, this study did not clearly state if creatine supplementation was administered concurrent with resistance training. Bemben et al [24] have shown no additional benefits of creatine alone or combined with whey protein for improving strength and muscle mass after a progressive 14 weeks (3 days per week) resistance training program in older men. These conflicting results can be explained by the possibility that the supplemented groups were formed by a greater amount of non-responders or even because creatine supplementation was administered on the training days only (3 times a week). This strategy has not been adequately tested as effective in middle aged and older men for maintaining post loading elevated creatine stores [5].
Stronger muscles improve performance in a variety of sports. Sport-specific training routines are used by many competitors. These often specify that the speed of muscle contraction during weight training should be the same as that of the particular sport. Sport-specific training routines also often include variations to both free weight and machine movements that may not be common for traditional weightlifting.
Heath bent his legs — each thigh about 32 inches around, bigger than his waist — and lifted the black case. Inside was his latest Mr. Olympia trophy. In bodybuilding, it is called the Sandow, and Heath has won the last six, most recently in Las Vegas in September. Arnold Schwarzenegger, still the world’s most famous bodybuilder, won six in a row, too, and then a seventh a few years later. Two men, Lee Haney and Ronnie Coleman, have won eight.

This cellular influx may also decrease protein oxidation rates, which leads to increases in nitrogen balance and indirectly increases muscle mass.[379] This lowering of protein oxidation is from signaling changes caused vicariously through cell swelling[380][381] and appears to upregulate 216 genes[378] in a range of 1.3 to 5-fold increases, with the largest increase seen in the protein involved in satellite cell recruitment, sphingosine kinase-1. Most importantly for muscle hypertrophy, the protein content of PKBa/Akt1, p38 MAPK, and ERK6 increased 2.8+/-1.2 fold.[378] Sixty-nine genes are also downregulated after creatine supplementation, to less notable degrees.
Kilduff, L. P., Georgiades, E., James, N., Minnion, R. H., Mitchell, M., Kingsmore, D., Hadjicharlambous, M., and Pitsiladis, Y. P. The effects of creatine supplementation on cardiovascular, metabolic, and thermoregulatory responses during exercise in the heat in endurance-trained humans. Int J Sport Nutr Exerc Metab 2004;14:443-460. View abstract.
Homocyteine (normal serum range of 5-14µM) is known to adversely affect motor control in genetically susceptible people when their levels exceed 500µM, which is usually associated with genetically induced deficiencies of B12.[360][361] In these particular instances (assessed by rats fed homocysteine to increase serum levels to such a high level[362][363]) it appears that administration of 50mg/kg creatine (injections) to these rats can protect dysfunction in muscle metabolism (pyruvate kinase activity, Krebs cycle intermediates, and muscle cell viability) induced by homocysteine.[363]
Overtraining occurs when a bodybuilder has trained to the point where his workload exceeds his recovery capacity. There are many reasons why overtraining occurs, including lack of adequate nutrition, lack of recovery time between workouts, insufficient sleep, and training at a high intensity for too long (a lack of splitting apart workouts). Training at a high intensity too frequently also stimulates the central nervous system (CNS) and can result in a hyperadrenergic state that interferes with sleep patterns.[51] To avoid overtraining, intense frequent training must be met with at least an equal amount of purposeful recovery. Timely provision of carbohydrates, proteins, and various micronutrients such as vitamins, minerals, phytochemicals, even nutritional supplements are acutely critical. A mental disorder informally called “bigorexia” (by analogy with anorexia) may be held accountable of some people overtraining. Sufferers feel as if they are never big enough or muscular enough, which forces them to overtrain in order to try and reach their goal physique.[52]
This suppression of creatine synthesis is thought to actually be beneficial, since creatine synthesis requires s-adenosyl methionine as a cofactor and may use up to 40-50% of SAMe for methylation[35][36][122] (initially thought to be above 70%, but this has since been re-evaluated[122]) though the expected preservation of SAMe may not occur with supplementation.[487] Reduced creatine synthesis, via preserving methyl groups and trimethylglycine (which would normally be used up to synthesize SAMe), is also thought to suppress homocysteine levels in serum,[37] but this may also not occur to a practical level following supplementation.[487]
^ Mangano, Kelsey M.; Sahni, Shivani; Kiel, Douglas P.; Tucker, Katherine L.; Dufour, Alyssa B.; Hannan, Marian T. (February 8, 2017). "Dietary protein is associated with musculoskeletal health independently of dietary pattern: the Framingham Third Generation Study". The American Journal of Clinical Nutrition. 105 (3): 714–722. doi:10.3945/ajcn.116.136762. PMC 5320406. PMID 28179224 – via ajcn.nutrition.org.
Naturally produced in the kidneys, pancreas and liver, creatine is transported to muscle tissue where it is transformed into creatine phosphate, from which the energy molecule ATP is produced to regenerate the muscles' ability to contract and generate power during short-burst (anaerobic) activity. This translates to more productive workouts and faster muscle growth.

Having a spotter nearby is particularly important when using free weights. Even someone in great shape sometimes just can't make that last rep. It's no big deal if you're doing biceps curls; all you'll have to do is drop the weight onto the floor. But if you're in the middle of a bench press — a chest exercise where you're lying on a bench and pushing a loaded barbell away from your chest — it's easy to get hurt if you drop the weight. A spotter can keep you from dropping the barbell onto your chest.

This cellular influx may also decrease protein oxidation rates, which leads to increases in nitrogen balance and indirectly increases muscle mass.[379] This lowering of protein oxidation is from signaling changes caused vicariously through cell swelling[380][381] and appears to upregulate 216 genes[378] in a range of 1.3 to 5-fold increases, with the largest increase seen in the protein involved in satellite cell recruitment, sphingosine kinase-1. Most importantly for muscle hypertrophy, the protein content of PKBa/Akt1, p38 MAPK, and ERK6 increased 2.8+/-1.2 fold.[378] Sixty-nine genes are also downregulated after creatine supplementation, to less notable degrees.
The creatine transporter is a sodium[139][140] and chloride[141][142] dependent membrane-associated transporter that belongs to the Na+/Cl-dependent family of neurotransmitter transporters.[143] In muscle cells and most other cell types,[131][141] the isomer of the creatine transporter is known as SLC6A8 (solute carrier family 6, member 8). SLC6A8 is encoded by the gene present on the Xq28 region of the human X-chromosome and is expressed in most tissues.[144] A related gene encoding a creatine transporter variant has also been identified at 16p11.1 that is expressed exclusively in the testes.[145] These two transporters share 98% homology.[144][145]
The NitroSurge pre-workout supplement by Jacked Factory aims to get you pumped and focused before a gym session. Besides L-Citrulline, this supplement also contains performance-enhancing betaine anhydrous and beta alanine. It also contains L-theanine which has shown to inhibit nerve cell damage in one study.  For energy-boosting benefits, the NitroSurge is also equipped with caffeine and AstraGin for energy metabolism. Before you buy, consider if you fall under the following circumstances in which this pre-workout would be beneficial to you:
Heath has 1.8 million Instagram followers, 300,000 Twitter followers, a global fan base and a growing portfolio of muscle magazine covers. He competes in just one competition a year, Mr. Olympia, for which he won the $400,000 first prize this year. He spends the rest of the year staying in shape and flying hundreds of thousands of miles for appearances, conferences and meetings. He has five sponsors, led by Ultimate Nutrition, a supplement company. All told, he earns more than $1 million a year, his agent said.
I’m glad you found some good information from this article. For any of these supplements, I would suggest talking to your doctor and pharmacist. I would suggest thinking about why you are interested in taking testosterone. Are you looking to increase muscle size? Bulk up? Knowing your fitness goals will help you determine which products are appropriate for you.
^ Jump up to: a b Barcelos RP, Stefanello ST, Mauriz JL, Gonzalez-Gallego J, Soares FA (2016). "Creatine and the Liver: Metabolism and Possible Interactions". Mini Reviews in Medicinal Chemistry. 16 (1): 12–8. doi:10.2174/1389557515666150722102613. PMID 26202197. The process of creatine synthesis occurs in two steps, catalyzed by L-arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT), which take place mainly in kidney and liver, respectively. This molecule plays an important energy/pH buffer function in tissues, and to guarantee the maintenance of its total body pool, the lost creatine must be replaced from diet or de novo synthesis.
Anti-cancer effects have been observed with the creatine analogue cyclocreatine[456][104][457] and have been replicated with creatine itself. These effects tend to be a reduction in which the rate of implanted tumors progresses.[458][459] It is suspected that these observed effects (inhibition of growth or attenuation of the rate of growth) are not due to the bioenergetic effect of creatine, secondary to creatine kinase. These anti-cancer effects do not have a known reliability, as the expression of creatine kinase varies widely based on the type of tumor.[460] However, some studies suggest an inverse relationship between tumor progression in mice and concentrations of creatine in cells, with creatine depletion coinciding with tumor development.[460]
Anti-depressive effects have been noted in woman with major depressive disorder when 5g of creatine monohydrate was supplemented daily for 8 weeks in combination with an SSRI. Benefits were seen at week two and were maintained until the end of the 8-week trial.[253] The improvement in depressive symptoms was associated with significantly increased prefrontal cortex levels of N-acetylaspartate, a marker of neuronal integrity,[254] and rich club connections, which refers to the ability of nerons to make connections to one another.[255] 

Creatine ethyl ester increases muscle levels of creatine to a lesser degree than creatine monohydrate.[72] It may also result in higher serum creatinine levels[73] due to creatine ethyl ester being converted into creatinine via non-enzymatic means in an environment similar to the digestive tract.[74][75] At equal doses to creatine monohydrate, ethyl ester has failed to increase water weight after 28 days of administration (indicative of muscle deposition rates of creatine, which are seemingly absent with ethyl ester).[76] 


Do standard squats with a weighted bar. Place enough weight on a bar and rack so that it's a little lower than shoulder height. It should be heavy enough that doing a squat is difficult, but not impossible. If you're a beginner, this may mean using a bar without any weight to start with. Duck under the bar and stand up so that the bar rests comfortably on your trapezius muscles, just below the neck. Keep your knees slightly bent and your legs slightly wider than shoulder width. Lift the bar up off the rack and move backwards one step.
HMB supplementation is claimed to build muscle size and strength and promote fat loss in conjunction with a strength program. Studies of HMB have shown some benefit to strength athletes in building muscle bulk but the benefits are relatively small and the cost of HMB is high. The effective dose seems to be 3 grams/day divided into 1 gram three times a day. Probably not worth taking. Beta-alanine is the new guy on the block and has not been evaluated sufficiently in my view. It may provide some advantage in high-intensity sports like weight training but it’s much too early to know that it does. Some early studies are flawed. Save your money or try creatine instead.
Activation of NMDA receptors is known to stimulate Na+,K+-ATPase activity[218] secondary to calcineurin,[219] which which has been confirmed with creatine in hippocampal cells (0.1-1mM trended, but 10mM was significant). This is blocked by NMDA antagonists.[220] This increase in Na+,K+-ATPase activity is also attenauted with activation of either PKC or PKA,[220] which are antagonistic with calcineurin.[219][221]
2-4 Minutes Rest: Ideal for “tension exercises,” which includes most primary compound exercises. I personally take 3 minutes for the big stuff, sometimes going into the 3-4 minute range depending on exactly what I’m doing and what I feel like I need at the time. Since making strength gains is the main focus of these exercises, longer rest periods like this will be optimal for making it happen.
In vitro, creatine (0.125mM or higher) can reduce excitotoxicity from glutamate, which is thought to be secondary to preserving intracellular creatine phosphate levels.[209] Glutamate-induced excitotoxicity is caused by excessive intracellular calcium levels resulting from ATP depletion. Since high levels of calcium inside the cell are toxic, ATP preserves membrane integrity,[210] in part by promoting calcium homeostasis. When ATP is depleted, the sodium-potassium ATPase pump (Na+,K+-ATPase) stops working, leading to sodium accumulation in the cell. This reduces the activity of the sodium-calcium exchange pump, which, alongside a lack of ATP, reduces calcium efflux through the Na+,K+-ATPase. Thus, ATP depletion leads to intracellular calcium overload, loss of membrane potential, and excitotoxic cell death. Therefore, by helping preserve ATP levels, creatine is protective against excitotoxicity. This protective effect was noted after either creatine preloading or addition up to 2 hours after excitotoxicity.[209] Protection from glutamate-induced toxicity also extends to glial cells[211] and is additive with COX2 inhibition.[212]
Increasing creatine levels in skeletal muscle to 687% of baseline (0.5mM creatine, thought to be equivalent to 5g creatine[135]) doesn’t seem to per se increase glucose uptake, but increases glucose oxidation (140% of baseline)[341] which is due to a two-fold increase in the activity of α1 and α2 subunits of AMPK, a potency comparable to 1mM of the reference drug AICAR.[341] Glucose uptake associated with AMPK has indeed been noted in diabetic people who are undergoing physical exercise[342] and in contracting skeletal muscle cells,[153][330] but according to rat[343][344][345] and in vitro studies of cells not being contracted,[341] this is not a per se effect of non-exercising tissue but an augmentation of exercise-induced glucose uptake.
Homocysteine is an endogenous metabolite involved in methylation processes in the body. Mildly elevated homocysteine appears to be an independent risk factor for both cardiovascular[302] and atherosclerotic disease,[303] where if the 8-10μM normal range is elevated by around 5μM, it is thought to confer 60-80% greater risk of atherosclerotic disease[303]. Although it may not independently cause problems,[304] it may play a causative role in the context of the whole body system, since it is atherogenic by augmenting LDL oxidation[305] and promoting conversion of macrophages into foam cells.[306]
The first open label trial on ALS failed to significantly alter lung function as assessed by FEV (when comparing the rate of decline pretreatment relative to treatment).[545] Creatine has elsewhere failed to benefit lung function at 5g daily for months relative to control[546] and failed to significantly attenuate the rate of lung function deterioration over 16 months at 10g daily[505] and 5g daily over nine months.[507]
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