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]
The exercises that allow you to use the greatest amount of weight are the ones that help you build muscle the fastest. These also happen to be the lifts that allow for the greatest percentage of increases in loading. We’re talking compound (multi-joint) exercises here, done with free weights. You’re not going to grow at nearly the same rate with a workout comprising machine exercises and isolation movements.
Creatine may preserve dopamine synthesis in the striatum of mice (while protecting against dopaminergic depletion) when fed to mice at 2% of the diet for one week prior to MPTP toxicity[230]. This is possibly secondary to increasing tyrosine hydroxylase activity, the rate-limiting step of dopamine biosynthesis.[210][235] Two percent creatine was as protective as 0.005% rofecoxib (a COX2 inhibitor), but the two were additive in their protective effects (highly synergistic in regard to DOPAC by normalizing it, but not synergistic in preserving HVA).[230]
It turns out yoga isn’t the only form of exercise that could strengthen your inner self. In fact, one study comparing the effects of hatha yoga and resistance exercise found that both activities improved mental health and wellbeing. Each group was less depressed, and the folks pumping iron enjoyed improved body image, too. “We know that all exercise improves mood,” explains Jeffrey A. Katula, PhD, associate professor of health and exercise science at Wake Forest University in Winston-Salem, North Carolina. “But I think resistance training provides something different emotionally to people.”
Parashos, S. A., Swearingen, C. J., Biglan, K. M., Bodis-Wollner, I., Liang, G. S., Ross, G. W., Tilley, B. C., and Shulman, L. M. Determinants of the timing of symptomatic treatment in early Parkinson disease: The National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) Experience. Arch Neurol. 2009;66(9):1099-1104. View abstract.
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]
There have also been concerns that creatine can cause kidney damage, and doctors warn that people with a history of kidney disease or conditions, such as diabetes, that increase the risk of kidney problems should steer clear of the supplement. Combining creatine with nephrotoxic drugs — drugs that might damage the kidneys — like nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (advil or motrin) and naproxen sodium (Aleve), should also be avoided, according to the U.S. Department of Health and Human Services. (1)
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.
A: At the end of the day, the most important variable regarding weight gain or loss is calorie consumption. However, meal frequency and timing around activity can both influence workout intensity and duration thus potentially allowing for further improvements in body composition. Remember, muscle growth isn’t a pulsatile process, it doesn’t just acutely spike and then return to baseline so if there aren’t circulating amino acids within the blood stream then they’ll have to be broken down from muscle as this is the highest form of concentrated amino acids within the body. That being said, it would probably be a good idea to consume anywhere from 3-6 meals spread throughout the day depending upon your schedule and preference. Ideally, we want to stimulate anabolism through food every 3-5 hours.
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]

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]
In particular situations, a coach may advise performing the valsalva maneuver during exercises which place a load on the spine. The vasalva maneuver consists of closing the windpipe and clenching the abdominal muscles as if exhaling, and is performed naturally and unconsciously by most people when applying great force. It serves to stiffen the abdomen and torso and assist the back muscles and spine in supporting the heavy weight. Although it briefly increases blood pressure, its is still recommended by weightlifting experts such as Rippetoe since the risk of a stroke by aneurysm is far lower than the risk of an orthopedic injury caused by inadequate rigidity of the torso.[10] Some medical experts warn that the mechanism of building "high levels of intra-abdominal pressure (IAP)...produced by breath holding using the Valsava maneuver", to "ensure spine stiffness and stability during these extraordinary demands", "should be considered only for extreme weight-lifting challenges — not for rehabilitation exercise".[11]
While this nonessential amino acid may not deliver earth-shattering PRs or extreme muscle growth, it does play an important role in repair and recovery. Glutamine works by removing excess ammonia, which can accumulate during intense exercise, helping to regulate your body's acid-base balance. Individuals who are engaged in heavy resistance training, two-a-day training splits, or are in a calorie deficit may benefit from the extra support of glutamine supplementation.
Now, while all three are definitely beneficial to the process, I’d consider metabolic stress and muscular damage to be of secondary and tertiary importance, respectively. In addition, they are also things that will pretty much take care of themselves when implementing the workout guidelines and recommendations we’ve already covered (namely for volume, rep ranges, rest periods and exercise selection).
Creatine levels in the blood tend to return to baseline (after a loading with or without the maintenance phase) after 28 days without creatine supplementation.[152][200][201] This number may vary slightly from one individual to another, and for some may exceed 30 days.[202] Assuming an elimination rate of creatinine (creatine’s metabolite) at 14.6mmol per day,[35][201] six weeks of cessation is approaching the upper limit for serum creatine to completely return to baseline.
Of the three, protein will of course play the most important role in the muscle building process (like calories, it’s one our required “supplies”), although fat and carbs will still be important for other reasons which range from optimizing hormone production (e.g. testosterone, the muscle building hormone) to enhancing training performance and recovery.

According to the abstract, in the stratified analyses by forms of aerobic exercise, weekly resistance exercise of 1 time or 1-59 minutes was associated with lower risks of total cardiovascular events and cardiovascular disease, regardless of meeting the aerobic exercise guidelines. The analysis showed that resistance training reduced the risk of cardiovascular events in 2 ways: training had a direct association with cardiovascular risk, and resistance training indirectly lowered cardiovascular risk by decreasing body mass index. 
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