But muscle can’t turn into fat, just like mud can’t turn into gold. If you quit lifting, your muscles mass will decrease over time because there’s no training to stimulate your body to keep it. And your body-fat level will increase if you don’t start eating less (since you burn less). The obvious solution when you stop lifting is to also stop eating so much.
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.)
Most causes of brain injury (calcium influx, excitotoxicity, lipid peroxidation, reactive oxygen intermediates or ROIs) all tend to ultimately work secondary to damaging the mitochondrial membrane and reducing its potential, which ultimately causes cellular apoptosis.[258][259][260][261] Traumatic brain injuries are thought to work vicariously through ROIs by depleting ATP concentrations.[262][263] Creatine appears to preserve mitochondrial membrane permeability in response to traumatic brain injury (1% of the rat’s diet for four weeks),[264] which is a mechanism commonly attributed to its ATP-buffering ability.

One case study exists of a man with focal segmental glomerulosclerosis who experienced an accelerated rate of GFR decline during supplementation (5g thrice daily for loading, then a 2g maintenance for seven weeks) which was partially reversed upon supplement cessation. This was deemed strong circumstantial evidence, and the brand of supplement was not named.[616] Elsewhere, interstitial nephritis associated with creatine supplementation has been reported in a man, although symptoms arose four weeks after supplementation started with no evidence to support correlation.[617] Some studies involving athletes and various dietary supplements have attempted to draw a correlation with creatine and cases of rhabdomyolysis.[618][619][620][621] Finally, one study in a diabetic person ingesting both metformin and creatine resulting in metabolic acidosis has attempted to place causation on creatine, but it did not establish causation or circumstantial evidence.[622]
Creatine concentration is normally increased in the placenta and brain in the midgestation phase until term, with further increases in the brain for another two weeks after birth.[529] This effect appears to be due to the fetus itself expressing the creatine enzymes of synthesis (AGAT and GAMT) after 5% of the gestation time has passed (0.9 days in spiny mice).[529] Despite creatine normally suppressing AGAT when supplemented at high concentrations,[29][30] it appears that maternal supplementation of the diet with 5% creatine from the halfway point of pregnancy until term does not alter creatine synthesis in the newborn (no alterations in either AGAT or GAMT), nor does it affect the creatine transporter.[530] 

Other human studies have yielded mixed results concerning creatine’s influence on triglyceride levels. In healthy male football players, creatine supplementation (5g monohydrate daily) over eight weeks did not influence triglyceride levels[324] but in martial artists given approximately 3.5g daily, a statistically significant increase in triglycerides was found despite no changes in total cholesterol.[325] In people with cardiovascular complications, given an exercise program and creatine, no significant change in triglycerides was noted relative to a placebo control group, which was also exercising.[326]

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] 
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.
You don’t have to, but you can. The typical creatine dose is 5 grams once or twice per day, but it’s sometimes suggested that one should “load” creatine by taking 20 to 25 grams per day for the first week of usage. This is then followed with 3 to 4 weeks of 5 grams per day, then a break for a week or two, then repeat. This may bring about more acute increases in strength and muscle size — creatine will “work” more quickly, in other words — but it’s not necessary.
While many of the claims are based on scientifically based physiological or biochemical processes, their use in bodybuilding parlance is often heavily colored by bodybuilding lore and industry marketing and as such may deviate considerably from traditional scientific usages of the terms. In addition, ingredients listed have been found at times to be different from the contents. In 2015, Consumer Reports reported unsafe levels of arsenic, cadmium, lead and mercury in several of the protein powders that were tested.[7]
Creatine Ethyl Ester, or CEE for short, is a powdered form of creatine which has an ethyl group attached to the creatine. This is said to make the creatine more easily absorbed in the human body which would allow you to benefit the most. The studies have not been entirely conclusive as to whether CEE is better than creatine monohydrate. Since Creatine monohydrate is the single most researched form of creatine, it is
References to any non-Onnit entity, product, service, person or source of information in this or any other Communication should not be considered an endorsement, either direct or implied, by the host, presenter or distributor of the Communication. The host(s), presenter(s) and/or distributor(s) of this Communication are not responsible for the content of any non-Onnit internet pages referenced in the Communication. Onnit is not liable or responsible for any advice, course of treatment, diagnosis or any other information or services you chose to follow without consulting a qualified medical professional. Before starting any new diet and/or exercise program, always be sure to check with your qualified medical professional.
Rheumatoid arthritis. Early research shows that taking creatine by mouth daily increases lean muscle mass and may improve muscle strength, but does not improve physical functioning in adults with rheumatoid arthritis. In children, taking a specific supplement containing creatine and fatty acids twice daily for 30 days might reduce pain and swelling. But the effects of creatine alone are not clear.
Unfortunately, many people haven't gotten the message that strong is in. Indeed, statistics on strength training are grim: According to the Centers for Disease Control and Prevention (CDC), less than 30 percent of American adults engage in muscle-strengthening activities like lifting weights or doing push-ups at least twice a week—the recommendations set out by the government. 

^ Jump up to: a b c d Brosnan ME, Brosnan JT (August 2016). "The role of dietary creatine". Amino Acids. 48 (8): 1785–91. doi:10.1007/s00726-016-2188-1. PMID 26874700. The daily requirement of a 70-kg male for creatine is about 2 g; up to half of this may be obtained from a typical omnivorous diet, with the remainder being synthesized in the body ... More than 90% of the body’s creatine and phosphocreatine is present in muscle (Brosnan and Brosnan 2007), with some of the remainder being found in the brain (Braissant et al. 2011). ... Creatine synthesized in liver must be secreted into the bloodstream by an unknown mechanism (Da Silva et al. 2014a)


You burn calories during strength training, and your body continues to burn calories after strength training (just like you do after aerobic exercise), a process called "excess post-exercise oxygen consumption" or EPOC, according to the American Council on Exercise. (13) When you do strength, weight, or resistance training, your body demands more energy based on how much energy you’re exerting (meaning the tougher you’re working, the more energy is demanded). That means more calories burned during the workout, and more calories burned after the workout, too, while your body is recovering to a resting state.
Negative regulators of the creatine transporter (CrT) are those that, when activated, reduce the activity of the CrT and overall creatine uptake into cells. As noted above, CrT activity is positively regulated by mTOR.[158] Consistent with the well-known role of AMPK as a suppressor mTOR signaling,[177] CrT activity has also been shown to be inhibited in response to AMPK activation in kidney epithelial cells.[178] Since AMPK suppresses mTOR via upstream TSC2 activation,[179] the negative regulation of AMPK on CrT activity in these cells appears to occur through an indirect mechanism. Although indirect, activation of AMPK has been noted to reduce the Vmax of the CrT without altering creatine binding, and is involved in internalizing the receptors.[178] This pathway seems to max out at around 30% suppression, with no combination of mTOR antagonists and AMPK inducers further suppressing creatine uptake.[178]
While creatine's influence on physical performance has been well documented since the early twentieth century, it came into public view following the 1992 Olympics in Barcelona. An August 7, 1992 article in The Times reported that Linford Christie, the gold medal winner at 100 meters, had used creatine before the Olympics. An article in Bodybuilding Monthly named Sally Gunnell, who was the gold medalist in the 400-meter hurdles, as another creatine user. In addition, The Times also noted that 100 meter hurdler Colin Jackson began taking creatine before the Olympics.[12][13]
Creatine citrate is creatine bound to citric acid, or citrate. Creatine citrate does not differ greatly from monohydrate in regard to absorption or kinetics.[83] Note that creatine citrate is more water-soluble than monohydrate,[84] but creatine absorption is generally not limited by solubility. The increased water solubility may play a factor in palatability.
Bodybuilders also train small muscles with a similar volume, frequency and intensity of their larger muscles. Strength athletes laugh at this. “Curls are a waste of time” is a common phrase you will hear hurled at a bodybuilder. This is SILLY. Although big compound movements should be most people’s resistance training priority, smaller muscle group focus work has some benefits for every athlete. Bicep tears are quite common among strength athletes, especially strong men and powerlifters. This happens because these competitors will lift tremendous weights with their backs, but their biceps are the weak link. Many of these injuries could be prevented with some good old-fashioned bodybuilder type isolation work. If you are only as strong as your weak link, doesn’t it make sense to make those weak links strong ones?

Although creatine is a natural component of food, the amount of food required to supersaturate the muscle with PCr may not be feasible. For example, it could require 22 pounds of meat daily [8]. If creatine monohydrate is proven to be a safe and effective ergogenic aid, creatine supplementation may be the simplest way to increasing muscle stores. It may be beneficial to avoid caffeine if taking creatine supplements. One study showed that caffeine diminished strength gains seen with creatine use [9].


Rheumatoid arthritis. Early research shows that taking creatine by mouth daily increases lean muscle mass and may improve muscle strength, but does not improve physical functioning in adults with rheumatoid arthritis. In children, taking a specific supplement containing creatine and fatty acids twice daily for 30 days might reduce pain and swelling. But the effects of creatine alone are not clear.

Despite the fact that BCAAs may offer some benefits, you should keep in mind that these three amino acids are also present in any quality whey protein that you purchase. You can also get these essential amino acids from food sources. Basically, as long as you’re meeting your daily protein intake goals, you’re probably getting enough of these essential amino acids. Research supports this approach. So, why spend more on another supplement?
Finally, starvation (nutrient deprivation for four days) appears to increase activity of the creatine transporter secondary to decreasing serine phosphorylation (SGK target)[173] with no influence on tyrosine phosphorylation (c-Src target).[173] Starvation-induced increases in creatine influx do not necessarily mean more phosphocreatine, however, due to a depleted cellular energy state.[173]
After all, we want you to be CONFIDENT and not overwhelmed, as the sooner you start strength training, the sooner you learn the ropes and start to make progress! We cover all of this in our free guide, Strength 101: Everything You Need to Know, along with free workout plans – grab all the goodies fo’ free when you join our worldwide Rebellion with your email in the box below!
Earlier during your workout, you might have thought you were starting to see some muscle definition. "Called transient hypertrophy, or a muscle pump, this physiological phenomenon occurs when blood rushes to your muscles to supply them with workout-powering fuel and even jump-start the recovery process," explains certified strength and conditioning specialist Samuel Simpson, co-owner and vice president of B-Fit Training Studio in Miami. He notes that this muscle pump often starts mid-workout and subsides within a few hours after leaving the gym. And as the muscle pump deflates, it's easy to lose determination.

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.


Studies that use a dosage range typical of creatine supplementation (in the range of 5g a day following an acute loading period) note increases to total body water of 6.2% (3.74lbs) over 9 weeks and[608] 1.1kg over 42 days.[609] Interestingly, some studies comparing creatine paired with training against training itself fail to find a significant difference in percentage of water gained (which is inherently to activity) with standard oral doses of creatine[609][607][610] (although low dose creatine supplementation of 0.03g/kg or 2.3g daily doesn’t appear to increase water retention[611]) despite more overall water weight being gained, due to an equal gain of dry mass in muscles. One study has quantified the percentage increase in mass of muscle cells to be 55% water, suggesting the two groups are fairly equal.[609]
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 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]
Entry into neural tissues in general is mediated by the secondary creatine transporter (CrT-2) known as SLC6A10,[186] which is the same transporter that is active in a male’s testicles.[145] CrT-2 belongs to the family of SLC6 transporters that act to move solutes across the membrane by coupling transport with sodium and chloride.[187][188] Genetic deletions in the 16p11.2 region, which encodes both SLC6A8[189] and SLC6A10[186] can result in severe mental retardation in humans and is one of the causes of “Creatine Deficiency Syndrome.” Creatine Deficiency Syndrome is not only caused by lack creatine transporter expression, however, as creatine synthesis is also critical for neural function.[190].[189] Retardation caused by defective creatine synthesis[31] can be reversed with creatine supplementation and dietary changes.[191]
It may seem odd to put such a common supplement as minerals on this list, but few people are aware that minerals are enzyme activators. Many vitamins, on the other hand, are coenzymes, which means that without minerals they're useless. Many minerals, such as zinc and chromium, also interact with various anabolic hormones, such as testosterone, growth hormone and insulin.
At the end of the day, you have to focus on how you feel. “Listen to your body,” says Davis. “It tells you when it needs a day off.” As a rule of thumb, take a rest day if your perceived pain is above a seven on a scale of 10, Davis advises. Or, focus on a different body part (say, if your legs are sore, focus on upper-body moves). Can't stop, won't stop—at least, till your next rest day.
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. 

For beginners, your own body weight might be enough to get you started. However, it can be hard to challenge your body without any additional resistance, so to progress, you'll need some equipment. If you decide to strength train at home, you'll want to invest in some basics, such as resistance bands, weights, and an exercise ball. Try to have a range of weights: a light set (3 to 5 pounds for women, 5 to 8 pounds for men), a medium set (5 to 10 pounds for women, 10 to 15 pounds for men), and a heavy set (10 to 20 pounds for women, 15 to 30 pounds for men).
Brain injury. Early research shows that taking creatine by mouth daily for 7 days increases the ability to exercise by increasing lung function in people with a spinal cord injury. However, other research shows that creatine does not improve wrist muscle or hand function. Early research also shows that taking creatine by mouth daily for 6 months reduces amnesia following a traumatic brain injury in children.
Some protein powders are loaded with junk. We recommend this grass-fed protein isolate because it is a non-GMO product and contains no artificial sweeteners. It is a US-based product, and the whey protein is cultivated from American cows. With 28 grams of protein in one scoop, one spoonful of this powder may provide the equivalent protein profile of a whole meal. What’s even better is that one scoop is only 120 calories. This powder gives you quite a bit of protein for minimal calories, keeping you lean.
Cyclocreatine appears to be passively diffused through membranes and not subject to the creatine transporter, which can be beneficial for cases where creatine transporter function is compromised (creatine non-response and SLG6A8 deficiency). Similar to other forms of creatine, it buffers ATP concentrations, although its efficacy as a supplement in otherwise healthy people is currently unknown. 

Muscle imbalances are quite common among strength athletes and are arguably the most common cause of their injuries. Many times this is due to a “weak link” in the kinetic chain of muscles that activate during their activity. Identifying the “weak” muscle and being able to feel, isolate and contract that “weak” muscle makes correctional exercise and rehab much easier. Bodybuilding training, with its focus on “feel” rather than movement, helps to train and develop the mind to muscle connection. This comes in handy when you need to train a muscle imbalance with correctional exercise and, in the case of injury, for rehab.
In your body, you can only store enough ATP for about 10 seconds of maximum exercise, this means that after those storages are depleted, it is up to your body to produce ATP to reach the demand your body is placing. [5] Creatine helps in the body by increasing stores of phosphocreatine which is the main ingredient used to create new ATP during intense exercise. By just supplementing creatine for 6 days, you can double your levels of creatine in your muscle storages, resulting in a higher capacity to create energy. [5]
Three additional studies suggest that creatine supplementation may not be beneficial for running velocity, sprint swimming performance, or a maximal cycling effort [7]. Short bouts of repeated anaerobic activity have shown some potential benefits with creatine supplementation use in a laboratory setting. However, creatine supplementation has not been shown to enhance single-event performance such as stationary cycling [16-19]. Taken together, these studies do not support creatine supplementation to enhance aerobic activities such as distance running.
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A: If your goal is the largest accrual of muscle mass possible then there may be some benefit to ingesting nutrients with a period of 30-60 minutes after your workout. Does this have to be a protein shake? No, but ideally it should be a meal lower in fat to enhance the digest rate of nutrients within the gastrointestinal tract. However, if you have just eaten a mixed macronutrient meal pre-workout then you should keep in mind that that meal is still likely digesting so there’s no need to throw down the weights after your last set and rush to your locker to slam a protein shake.

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.
Stand on one foot with the arch and heel hanging off of the edge of a step or platform. Hold onto something if you need help balancing. Drop your heel all the way down below the step, and then rise all the way up on your toes. Hold dumbbells to make it harder. If you can balance without holding on to something, you’ll work your core muscles, too. You'll also build more stable joints in the other leg.
Vegetarians and other people who have lower total creatine levels when they start taking creatine supplements seem to get more benefit than people who start with a higher level of creatine. Skeletal muscle will only hold a certain amount of creatine; adding more won't raise levels any more. This "saturation point" is usually reached within the first few days of taking a "loading dose."
^ 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.
A great analogy that I like is that the balance between training and recovery is like digging a hole. Each time you lift, you dig yourself deeper and make it harder to climb out of the hole. To get back out again, you have to fill in the hole to return to ground level, and the only way to fill it is with food and rest. If you overdo it in the gym by pushing too hard, you won’t be able to train as often or at a high capacity. Eventually, you’ll get injured.
Most of us have lives, or jobs, or school, or family, or whatever else that puts some kind of limit on when and how often we can work out. For example, are there certain days that you are able to work out on, and certain days you aren’t? Are you able to train 5 days per week, or would 3-4 be more ideal? Choosing a split that suits your personal schedule and is as convenient for you as possible will be crucial for adherence, and without adherence, nothing is going to work.
Based on the limited data on performance and safety, some authors have not identified any conclusions and do not recommend its consumption in regards to creatine supplementation in children and adolescents [52,54]. Conversely, according to the view of the ISSN [5], younger athletes should consider a creatine supplement under certain conditions: puberty is past and he/she is involved in serious competitive training; the athlete is eating a well-balanced caloric adequate diet; he/she as well as the parents approve and understand the truth concerning the effects of creatine supplementation; supplement protocols are supervised by qualified professionals; recommended doses must not be exceeded; quality supplements are administered.
In nonelite swimmers conducting an intermittent sprint protocol (Six 50m sprints every two minutes), supplementation of a creatine loading period was able to reduce the decrement in speed during the third sprint (2% decrement rather than a 5% decrement) but not the sixth sprint. There were no changes in plasma lactate or other biomarkers of fatigue.[396] When examining a single 50m sprint in amateur swimmers, a creatine loading period is able to reduce the time to complete the sprint by 4.6%, while it had no benefit for the 100m sprint.[397] When the loading phase was followed by three weeks maintenance in youth, there was no apparent benefit to sprint performance (50m sprint with five minutes rest followed by a 100m freestyle) despite benefits to a swim bench test (30s sprints with a five minute break in between).[398]

The materials and information provided in this presentation, document and/or any other communication (“Communication”) from Onnit Labs, Inc. or any related entity or person (collectively “Onnit”) are strictly for informational purposes only and are not intended for use as diagnosis, prevention or treatment of a health problem or as a substitute for consulting a qualified medical professional. Some of the concepts presented herein may be theoretical.
Does magnesium relieve migraines? Many people use magnesium, which is a naturally occurring mineral, to treat and prevent migraine headaches, especially those with aura. In this article, learn about the effectiveness of magnesium and discover whether there are any side effects or risks. We also list some of the foods that contain magnesium. Read now
More recent studies on the regulation of CrT creatine transport activity have identified the protein kinase (Janus-Activating Kinase 2) JAK2, which suppresses the rate of creatine uptake via CrT without affecting creatine binding.[181] JAK2 is a regulatory protein involved in stabilizing the cellular membrane and controlling water concentrations in response to osmotic stress.[182][183] Similar to c-Src (a positive creatine transport regulator), Jak2 can also be activated by growth hormone signaling.[169][184] The growth hormone receptor seems to activate these two factors independently, as gh-mediated activation of c-Src does not require JAK2.[168] Given that c-Src is a positive regulator of CrT, JAK2 is a negative regulator, and the fact that downstream signals from both are induced by growth hormone, it is tempting to speculate that JAK2 activation downstream of the gh receptor may function as a homeostatic response to limit c-src induced creatine uptake. This has not been studied, however, and the effects of gh-induced JAK2 signaling on CrT activity have not been examined.
Despite the fact that BCAAs may offer some benefits, you should keep in mind that these three amino acids are also present in any quality whey protein that you purchase. You can also get these essential amino acids from food sources. Basically, as long as you’re meeting your daily protein intake goals, you’re probably getting enough of these essential amino acids. Research supports this approach. So, why spend more on another supplement?
Kerksick, C. M., Wilborn, C. D., Campbell, W. I., Harvey, T. M., Marcello, B. M., Roberts, M. D., Parker, A. G., Byars, A. G., Greenwood, L. D., Almada, A. L., Kreider, R. B., and Greenwood, M. The effects of creatine monohydrate supplementation with and without D-pinitol on resistance training adaptations. J.Strength.Cond.Res. 2009;23(9):2673-2682. View abstract.
Weight training has also been shown to benefit dieters as it inhibits lean body mass loss (as opposed to fat loss) when under a caloric deficit. Weight training also strengthens bones, helping to prevent bone loss and osteoporosis. By increasing muscular strength and improving balance, weight training can also reduce falls by elderly persons. Weight training is also attracting attention for the benefits it can have on the brain, and in older adults, a 2017 meta analysis found that it was effective in improving cognitive performance.[38]
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]
Endurance exercise is also known to produce heat from skeletal muscle tissue, and an increase in internal temperature occurs when the production of heat (from metabolism) exceeds release. This increase in heat is accelerated when training in hot environments[390] and it is thought to be beneficial to retain water (hydration) during exercise, since more water allows a preservation of plasma volume (PV) and the sweat response reduces internal temperature.[391][392] This particular phenomena may only apply to endurance exercise, since creatine is able to increase sprint performance in heat, independent of altering the decline in PV and sweat rates.[393]

In otherwise healthy adults subject to leg immobilization for two weeks while taking 20g creatine daily during immobilization and then 5g daily during eight weeks of rehabilitation, it was noted that the creatine group failed to reduce atrophy during the immobilization (10% reduction in cross sectional area and 22-25% reduction in force output) despite preventing a decrease in phosphocreatine, yet experienced a significantly enhanced rate of regrowth and power recovery.[358] A similarly structured and dosed study has also noted greater expression of skeletal muscle, GLUT4 expression, and a 12% increase in muscle phosphocreatine content.[330]


Entry into neural tissues in general is mediated by the secondary creatine transporter (CrT-2) known as SLC6A10,[186] which is the same transporter that is active in a male’s testicles.[145] CrT-2 belongs to the family of SLC6 transporters that act to move solutes across the membrane by coupling transport with sodium and chloride.[187][188] Genetic deletions in the 16p11.2 region, which encodes both SLC6A8[189] and SLC6A10[186] can result in severe mental retardation in humans and is one of the causes of “Creatine Deficiency Syndrome.” Creatine Deficiency Syndrome is not only caused by lack creatine transporter expression, however, as creatine synthesis is also critical for neural function.[190].[189] Retardation caused by defective creatine synthesis[31] can be reversed with creatine supplementation and dietary changes.[191]
Cyclocreatine appears to be passively diffused through membranes and not subject to the creatine transporter, which can be beneficial for cases where creatine transporter function is compromised (creatine non-response and SLG6A8 deficiency). Similar to other forms of creatine, it buffers ATP concentrations, although its efficacy as a supplement in otherwise healthy people is currently unknown.
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