So, for example, with the moves above you'd do 15 squats followed by 15 push-ups. Take a little breather then repeat that two more times. Then you move on to your walking lunges and lat pull-downs (and repeat those three times total, too). You can really do anywhere from eight reps to 15 (and even just two sets, if you don't have time for three), but "it’s not a bad idea for beginners to start with a 15-rep range to get comfortable with the exercises," says Davis. And while there's some debate over whether three sets of an exercise is really best, "it’s a great beginner model," says Davis. Don't overcomplicate things when you're just getting started.
While the number of reps you do per set is important, of equal importance is the total number of reps you do per muscle group. The National Strength and Conditioning Association has determined that, to maximize growth, you need approximately 20–70 total reps per muscle group. Depending on which end of a rep range you’re working, this can be done in one session or over a few days (a training week, for instance), but that’s the spread you need to cover to see gains.

In the last week leading up to a contest, bodybuilders usually decrease their consumption of water, sodium, and carbohydrates, the former two to alter how water is retained by the body and the latter to reduce glycogen in the muscle. The day before the show, water is removed from the diet, and diuretics may be introduced, while carbohydrate loading is undertaken to increase the size of the muscles through replenishment of their glycogen. The goal is to maximize leanness and increase the visibility of veins, or "vascularity". The muscular definition and vascularity are further enhanced immediately before appearing on stage by darkening the skin through tanning products and applying oils to the skin to increase shine. Some competitors will eat sugar-rich foods to increase the visibility of their veins. A final step, called "pumping", consists in performing exercises with light weights or other kinds of low resistance (for instance two athletes can "pump" each other by holding a towel and pulling in turn), just before the contest, to fill the muscles with blood and further increase their size and density.
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.
If you decide to join a gym, know that you're not expected to know how all of the equipment works right off the bat—or what to do with it. Be sure to take advantage of the free orientation so you can learn how to properly use everything that's offered and set up a basic strength-training program. At the gym, machines are preferred for beginners, because they're quite safe: Most require little coordination and offer more stability than free weights while performing the movements. 
If you have been struggling in the gym, getting over a plateau can seem very daunting. You are training hard, eating healthy, yet the results still aren’t coming. Creatine is a supplement which will help you gain strength, build muscle, lose fat, and give the energy you need to attack your workouts with an intensity that are guaranteed to give you results!
Consuming sufficient high-quality protein is essential for building muscle. Current recommendations are to consume a minimum of 0.8g of protein for each kg of body weight, however, this is really only applicable to the average sedentary individual. Current evidence shows that to support muscle development, protein intake is the key, therefore the recommended 0.8g per kg should be increased to 1.5-2.0g of protein per kg of body weight. For an 80 kg individual, that would equate to 120-160 grams of protein per day.

Some of the most common minor side effects include stomach discomfort, nausea, and increased bowel movements. Other potential side effects may include headaches, bloating, and increased thirst. There is always the chance that a supplement could cause an allergic reaction. This can result in rashes, swelling, or difficulty breathing, depending on the severity of the reaction. This is another reason why starting out with lower doses of new products is advisable.
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.
“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.
I HATE that the resistance training community can be so tribal. I have been preaching to bodybuilders for years about the benefits of powerlifting, or Olympic lifting or kettlebells or even Crossfit style conditioning and many have been receptive. Learn from each other and achieve levels of fitness you simply could not have otherwise. Don’t brush off bodybuilding wisdom…it could be the missing factor in your program.
Skin degradation is caused by a loss of collagen and degradation of the extracellular matrix,[536] which is enhanced by UV radiation (produces reactive oxygen species which stimulate MMPs[537]) and contributes to skin integrity loss and wrinkling. Due to the stimulation of collagen being associated with a cellular surplus of energy[538] and intracellular stores of energy declining with age,[539][540] creatine has been investigated as a topical anti-aging agent. In vitro, creatine appears to be rapidly absorbed through the skin (52% within an hour, remaining similar at 3 hours) with most creatine found in the stratum corneum (79.6-86.5%) follwed by the epidermis (9-13.2%) and dermis (4.5-7.1%).[541] It is successful in stimulating collagen expression and procollagen secretion in fibroblasts, with the latter increasing to 449+/-204% of control.[541]
The creatine transporter (CrT) is positively regulated by proteins known to be involved in sensing and responding to the cellular energy state, including the mammalian target of rapamycin (mTOR[158]). Upon activation, mTOR stimulates SGK1 and SGK3[159][160] to act upon PIKfyve[161] and subsequently PI(3,5)P2[162] to increase CrT activity.[161] Beyond mTOR, SGK1 also is stimulated by intracellular calcium[163] and a lack of oxygen (ischemia).[164] Because transient ischemia is associated with increased reactive oxygen species (ROS) production after blood flow is restored (reperfusion) it has been hypothesized that muscle contraction may increase creatine uptake through a similar ROS-mediated mechanism.[165]
If you have hit a plateau, a good supplement could be all you need to pull yourself out of a slump and make the progress you want to be making. Creatine is widely known as the most effective sports supplement. Scientific studies have proven that creatine maximizes ATP production which is responsible for energy in your body. Essentially, creatine will give you more energy to allow you to do the things that will make you stronger.
The majority of your workouts should be comprised of compound exercises. Common examples include squats, deadlifts, lunges, bench presses, rows, pull-ups, lat pull-downs, overhead presses, and so on. Isolation exercises should definitely also be a part of your program, just a smaller part in comparison. Common examples include bicep curls, tricep extensions, chest flies, lateral raises, leg curls, leg extensions, calf raises, and so on.
While muscle growth is critical for bodybuilding, getting rid of extra fat is a necessity to improve your total physique. These supplements can help to increase your metabolism, forcing your body to burn away more of its fat stores. They can also slow down the digestion process to prevent excess fat and carbohydrates from entering the body and being stored.
How to maximize its effects: Take 20 grams of whey protein powder in the 30 minutes before working out, and take 40 grams within 60 minutes after training. Also consider taking 20-40 grams of whey immediately upon waking every morning to kick-start muscle growth. Your best bet is to choose a whey powder that contains whey protein hydrolysates (whey protein broken down into smaller fragments for faster digestion) or whey protein isolate.
The first thing you need is a weight training program that signals the muscle building process to begin. Research has shown that a well designed program will generate this “signal” via a combination of progressive tension overload (as in, getting stronger over time), metabolic stress (as in, fatiguing the muscle and getting “the pump”), and muscular damage (as in, actual damage to the muscle tissue itself).
A study using creatine at 0.02% of a face cream (confounded with 8% glycerol and 0.4% Guarana) was able to exert a skin-tightening effect over 6 weeks, reducing wrinkles and jowl volume.[541] Combination therapy has also been used with creatine and folic acid (both in vitro[543] and in vivo), resulting in increased skin firmness and reduced coarse and fine wrinkles.[544]
You may be wondering what conditions and medications contraindicate the use of creatine supplements. Creatine is contraindicated in people with kidney insufficiency or kidney disease. If you take diabetes medication, diuretics or acetaminophen, do not take a creatine supplement. Use caution if you regularly consume caffeine while taking a creatine supplement. Overall, if you are healthy and have gotten clearance from your doctor, consider this non-GMO creatine supplement.
Research shows that strength training is especially effective at raising EPOC. That’s because, generally speaking, strength-training sessions cause more physiological stress to the body compared to cardiovascular exercise, even higher-intensity cardio intervals. However, it’s worth noting that overall exercise intensity is what makes the biggest impact on EPOC. So squats, deadlifts, and bench presses with heavy weights are going to be much more effective at raising EPOC compared to bicep curls and triceps extensions with light weights.

A typical creatine supplementation protocol consists of a loading phase of 20 g CM/d or 0.3 g CM/kg/d split into 4 daily intakes of 5 g each, followed by a maintenance phase of 3-5 g CM/d or 0.03 g CM/kg/d for the duration of the supplementation period [5]. Other supplementation protocols are also used such as a daily single dose of around 3 – 6 g or between 0.03 to 0.1 g/kg/d [15,55] however this method takes longer (between 21 to 28 days) to produce ergogenic effects [5]. Sale et al [56] found that a moderate protocol consisting of 20 g CM taken in 1g doses (evenly ingested at 30-min intervals) for 5 days resulted in reduced urinary creatine and methylamine excretion, leading to an estimated increase in whole body retention of creatine (+13%) when compared with a typical loading supplementation protocol of 4 x 5 g/d during 5 days (evenly ingested at 3 hour intervals). This enhancement in creatine retention would lead to a significantly higher weight gain when people follow a moderate protocol ingestion of several doses of small amounts of CM evenly spread along the day.


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]
Weight training also provides functional benefits. Stronger muscles improve posture, provide better support for joints, and reduce the risk of injury from everyday activities. Older people who take up weight training can prevent some of the loss of muscle tissue that normally accompanies aging—and even regain some functional strength—and by doing so, become less frail.[33] They may be able to avoid some types of physical disability. Weight-bearing exercise also helps to prevent osteoporosis.[34] The benefits of weight training for older people have been confirmed by studies of people who began engaging in it even in their eighties and nineties.
Exercise is highly effective in increasing your lean body mass, which is essentially muscle. In a study published in 2012, progressive resistance training helped men ages 50 to 83 gain an average of 2.4 pounds of lean body mass over an average of 20.5 weeks. Progressive resistance training involves performing weight bearing exercises. In addition, you must slowly increase the challenge of the exercise over time by increasing the weight, reps and/or sets. Studies show that either increasing reps or weight amount will work. So, if you don’t want to lift more weight, you can just do more reps and still build muscle.
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.
In young rats given creatine in the diet at 2% of the diet for eight weeks, supplementation appears to increase bone mineral density (BMD) in the lumbar spine with a nonsignificant trend to increase BMD in the femur.[426] Despite the trend, the femur appeared to be 12.3% more resistant to snapping from mechanical stress associated with increased thickness.[426] Menopausal rats (ovarectomized) experience similar benefits, as supplementation of creatine (300mg/kg) for eight weeks during ovarectomy is able to increase phosphorus content of the bone and other biomarkers of bone health, although bone stress resistance was not tested.[427]
The right amount of workout: It is highly possible that the protein powder you are taking doesn’t work on your body. Supplements should only be taken if you have a rigorous workout schedule or else, it will turn out to be of no value. Most people just purchase a box of supplements without really doing the math, which is very important. Unless you find out the dosage that suits you, the amount of time you should dedicate for the workout and so on, you must not expect daydream the 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.
Although creatine can be bought commercially as a standalone product it is often found in combination with other nutrients. A prime example is the combination of creatine with carbohydrate or protein and carbohydrate for augmenting creatine muscle retention [5] mediated through an insulin response from the pancreas [69]. Steenge et al [70] found that body creatine retention of 5 g CM was increased by 25% with the addition of 50 g of protein and 47 g of carbohydrate or 96 g carbohydrate when compared to a placebo treatment of 5 g carbohydrate. The addition of 10g of creatine to 75 g of dextrose, 2 g of taurine, vitamins and minerals, induced a change in cellular osmolarity which in addition to the expected increase in body mass, seems to produce an up regulation of large scale gene expression (mRNA content of genes and protein content of kinases involved in osmosensing and signal transduction, cytoskeleton remodelling, protein and glycogen synthesis regulation, satellite cell proliferation and differentiation, DNA replication and repair, RNA transcription control, and cell survival) [25]. Similar findings have also been reported for creatine monohydrate supplementation alone when combined with resistance training [71].
Minor liver lesions (grade I, no grade II or III, pathology not indicative of toxicity) have been studied in SOD1 G93A transgenic mice (a research model for amyotrophic lateral sclerosis or ALS, but used in this study to assess a state of chronic pro-oxidative stress) for 159 days with 2% of feed intake and in CD-1 rats (seen as normal) over 56 days with 0.025-0.5mg/kg in CD-1 mice, although in Sprague-Dawley rats (normal controls) there were no significant differences noted even after 2% of feed intake for 365 days.[503] These observations appear to be due to the strain of the rodents used,[504][503] and human studies on amyotrophic lateral sclerosis (ALS; what the SOD1 G93A transgenic mice are thought to represent) lasting from nine to sixteen months with subjects supplementing with up to 10g of creatine daily have failed to find any abnormalities in serum biomarkers of liver or kidney health.[505][506][507]
In addition to being potentially harmful, some have argued that there is little evidence to indicate any benefit to using bodybuilding protein or amino acid supplements. "In view of the lack of compelling evidence to the contrary, no additional dietary protein is suggested for healthy adults undertaking resistance or endurance exercise".[18] In dispute of this, one more recent meta-analysis concluded that for athletes participating in resistance exercise training and consuming protein supplements for an average of 13 weeks, total protein intake up to 1.6 g per kg body weight per day would result in an increase in strength and fat-free mass, i.e. muscle, but that higher intakes would not further contribute. The muscle mass increase was statistically significant but modest - averaging 0.3 for all trials and 1.0 to 2.0 kg, for protein intake ≥ 1.6 g/kg/day.[3]
de Salles Painelli V, Alves VT, Ugrinowitsch C, et al. Creatine supplementation prevents acute strength loss induced by concurrent exercise. Eur J Appl Physiol 2014;114(8):1749-55.del Favero S, Roschel H, Artioli G, et al. Creatine but not betaine supplementation increases muscle phosphorylcreatine content and strength performance. Amino Acids 2012;42(6):2299-305. View abstract.
You may have heard hardcore lifters talk about things like "leg day," but when it comes to a beginner strength workout that's only a few days a week, a full-body workout is often the way to go (rather than splitting your days up by body part). "Full-body workouts maximize your caloric burn and the muscles worked each session," says Davis. The best way to do this is to pair one upper body exercise with one lower body exercise. "This way, the lower body has time to recover while the upper body works and vice-versa," says Davis. You should also aim for a balance between movements that feel like pulling and ones that feel like pushing. For example, Davis suggests pairing these exercises together:
At the end of the day, yes, strength training does impact your metabolism, but any boost you get will be minimal and completely secondary to all of the other health benefits of strength training. Any change in metabolism or increase in calorie burn will vary widely from person to person, and depends on so many factors: your genetics, eating habits, health conditions, what workout you do that day, how much sleep you’re getting, and even how stressed you are on any given day. But incorporating a couple of strength training sessions into your fitness routine is worth doing no matter what—you’ll feel yourself get stronger, and put yourself in a position to say healthier throughout life. Those are the best, most promising benefits to work for.
Recommended Dose: 3-6 grams before or during exercise. A ratio of two parts leucine to one part each of isoleucine and valine appears to be most beneficial. As Krissy Kendall, PhD, explains in "The Top 7 Supplements to Boost Endurance Performance," BCAAs can be just as effective for endurance athletes like runners, rowers, and cyclists as they can be for lifters and bodybuilders.
In muscle cells, the creatine transporter is predominantly localized to the sarcolemmal membrane. Western blot analysis of creatine transporter expression revealed the presence of two distinc protein bands, migrating at 55kDa and 70kDa on reducing SDS-PAGE gels.[147][148] The 73kDa band has been reported to be the predominant band in humans, with no differences based on gender.[148] A more recent report demonstrated that the 55kDa creatine transporter variant is glycosylated, forming the 73 kDa protein. Therefore, the 55 and 75kDa protein bands are actually immature and mature/processed forms of the creatine transporter protein, respectively.[149]

Another favorite bodybuilding supplement, creatine is an amino acid found in the body. The highest levels of this molecule are in your muscles and brain. It is made by your liver, pancreas and kidneys, but is also found in foods including meat, eggs and fish. Research has shown that it may help athletes including weightlifters who need short bursts of energy (5). In this study, creatine monohydrate proved to be an effective muscle builder. It works to improve body composition, muscle mass, strength and power.  Note that it was also more effective than other forms of creatine. How does it do this?
In muscle cells, the creatine transporter is predominantly localized to the sarcolemmal membrane. Western blot analysis of creatine transporter expression revealed the presence of two distinc protein bands, migrating at 55kDa and 70kDa on reducing SDS-PAGE gels.[147][148] The 73kDa band has been reported to be the predominant band in humans, with no differences based on gender.[148] A more recent report demonstrated that the 55kDa creatine transporter variant is glycosylated, forming the 73 kDa protein. Therefore, the 55 and 75kDa protein bands are actually immature and mature/processed forms of the creatine transporter protein, respectively.[149]
It’s important to remember that since everybody is different, these estimates are just that. How the numbers work out for each person will definitely vary. So many factors—like genetics, hormones, sleep, and diet—can change the rate at which our bodies burn calories. And some people may have a harder time than others when it comes losing fat or gaining muscle—again, there are so many factors at play and our body chemistries are all different. Strength training is important for many, many, many other reasons (more on that later), but if you’re looking to increase your metabolism, it’s important to have realistic expectations and know that strength training can make a difference, but probably won’t drastically affect how many calories you burn from one day to the next.
Lyoo, I. K., Yoon, S., Kim, T. S., Hwang, J., Kim, J. E., Won, W., Bae, S., & Renshaw, P. F. (2012, September). A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder. American Journal of Psychiatry. 169(9):937-45. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22864465
In 1912, Harvard University researchers Otto Folin and Willey Glover Denis found evidence that ingesting creatine can dramatically boost the creatine content of the muscle.[5][non-primary source needed] In the late 1920s, after finding that the intramuscular stores of creatine can be increased by ingesting creatine in larger than normal amounts, scientists discovered creatine phosphate, and determined that creatine is a key player in the metabolism of skeletal muscle. The substance creatine is naturally formed in vertebrates.[6]
In addition to the BBB, SLC6A8 is also expressed on neurons and oligodendrocytes,[192] but is relatively absent from astrocytes, including the astrocytic feet[193][194] which line 98% of the BBB.[195] Creatine can still be transported into astrocytes (as well as cerebellar granule cells) via SLC6A8, as incubation with an SLC6A8 inhibitor prevents accumulation in vitro. It seems to be less active in a whole brain model, relative to other brain cells.[196]

Do standard/oblique crunches. Lie down on a mat and position both arms behind your head without locking the hands. Bend your knees so that your feet are flat on the ground. Pushing the small of your back into the ground, slowly roll your shoulders off the ground only a couple of inches (not to a full sitting position). Don't use your momentum to help you up; use slow, regulated movements. Repeat 3 x 20.

Crave instant gratification? Strength training is a good motivator because you see progress quickly. “If you put someone on a walking program, it will take time before they perceive their body is changing,” explains Katula. “But with strength training, you can feel a difference in your muscles even after one session.” And it only takes a couple workouts before you’ll notice some muscle definition in the mirror. (Go ahead and flex. We dare you.)
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.
Creatine is found in many protein supplements at baseline in the form of creatine monohydrate. If you take a protein supplement, you may already be getting creatine. What makes this creatine so special? Like the protein supplement above, this creatine supplement contains no artificial sweeteners or dyes. It contains 5000mg of creatine per dose and includes certain compounds to increase the bioavailability of the creatine, allowing it to be better absorbed.
After a tough sweat, it's important to rehydrate your body: "Drink lots of water and thank your body for what it was just able to accomplish," says Davis. A balanced post-workout snack is also a good idea. Go for one with carbs refuel your glycogen stores (one of your body's main energy sources) and about 10 to 20 grams of protein to help build and repair your muscles. "Don’t overcomplicate it," says Davis. If you're lifting and weight loss is one of your goals, though, it's still important to keep calories in mind—a post-workout snack shouldn't be more than 150 to 200 calories. Here's a guide to how many calories you should be eating for weight loss.
If you’re exercising at your maximum intensity, your body literally can’t produce enough ATP to keep up. (10) That’s where creatine supplements come in: They can help increase your body’s stores of phosphocreatine (an organic compound of creatine and phosphoric acid that’s stored in your muscle tissue) to produce new ATP during high-intensity exercise.
In fact, in one new study comparing the effects of aerobic exercise versus resistance training on the psychological health of obese adolescents, researchers found that people in the resistance group experienced significantly greater self-esteem and perceived strength over four weeks. But what’s most interesting is that the feeling of getting stronger — rather than any measurable gains — was all it took to give them a boost.
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.
Weight training also provides functional benefits. Stronger muscles improve posture, provide better support for joints, and reduce the risk of injury from everyday activities. Older people who take up weight training can prevent some of the loss of muscle tissue that normally accompanies aging—and even regain some functional strength—and by doing so, become less frail.[33] They may be able to avoid some types of physical disability. Weight-bearing exercise also helps to prevent osteoporosis.[34] The benefits of weight training for older people have been confirmed by studies of people who began engaging in it even in their eighties and nineties.
Tribulus Terrestris: A fruit from the Mediterranean, this supplement has been used in the Indian traditional medicine of Ayurveda. In addition to helping increase testosterone, many people take it to increase libido and as a cardioprotective aid. (10) Unfortunately, despite the fact that there are claims that tribulus terrestris can increase testosterone levels, studies don’t back up these claims.  There is some evidence, however, that it may improve athletic performance. If you want to choose one of the supplements for men, this should be your pick.
In summary, creatine salts have been show to be less stable than CM. However the addition of carbohydrates could increase their stability [62]. The potential advantages of creatine salts over CM include enhanced aqueous solubility and bioavailability which would reduce their possible gastrointestinal adverse effects [63]. The possibility for new additional formulation such as tablets or capsules is interesting for its therapeutic application due to its attributed better dissolution kinetics and oral absorption compared to CM [63]. However more complete in vivo pharmaceutical analysis of creatine salts are required to fully elucidate their potential advantages/disadvantages over the currently available supplement formulations.
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]
JAK2 (Janus-Activating Kinase 2) is a novel protein that has been shown to suppress the activity of the creatine transporter CrT in vitro. The effects of JAK2 on CrT are not well-understood in vivo, however. Given that growth hormone activates both c-src (increases CrT activity) and JAK2- which has been found to decrease CrT activity, it is plausible that JAK2 may function as a negative-feedback regulator of creatine uptake. Future research is needed to better understand the role of JAK2 on CrT activity in vivo.
In regard to practical interventions, concurrent glycogen loading has been noted to increase creatine stores by 37-46% regardless of whether the tissue was exercised prior to loading phase.[176] It is important to note, however, that creatine levels in response to the creatine loading protocol were compared in one glycogen-depleted leg to the contralateral control leg, which was not exercised.[176] This does not rule out a possible systemic exercise-driven increase in creatine uptake, and the increase in creatine noted above[176] was larger than typically seen with a loading protocol (usually in the 20-25% range). Consistent with an exercise-effect, others have reported that exercise itself increases creatine uptake into muscle, reporting 68% greater creatine uptake in an exercised limb, relative to 14% without exercise.[153]
The maximum amount of creatine the body can store is about 0.3 gram per kilogram of body weight [6]. The creatine content of skeletal (voluntary) muscles averages 125 millimoles per kilogram of dry matter (mmol/kg/dm) and ranges from about 60 to 160 mmol/kg/dm. Approximately 60% of muscle creatine is in the form of PCr. Human muscle seems to have an upper limit of creatine storage of 150 to 160 mmol/kg/dm. Athletes with high creatine stores don't appear to benefit from supplementation, whereas individuals with the lowest levels, such as vegetarians, have the most pronounced increases following supplementation. Without supplementation, the body can replenish muscle creatine at the rate of about 2 g/day [7].
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]
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