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.
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It is suggested [16,37] that another mechanism for the effect of creatine could be enhanced muscle glycogen accumulation and GLUT4 expression, when creatine supplementation is combined with a glycogen depleting exercise. Whereas it has been observed [38] that creatine supplementation alone does not enhance muscle glycogen storage. Hickner et al [15] observed positive effects of creatine supplementation for enhancing initial and maintaining a higher level of muscle glycogen during 2 hours of cycling. In general, it is accepted that glycogen depleting exercises, such as high intensity or long duration exercise should combine high carbohydrate diets with creatine supplementation to achieve heightened muscle glycogen stores [39].
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."
There are positive correlations between positive orgasm experience in women and testosterone levels where relaxation was a key perception of the experience. There is no correlation between testosterone and men's perceptions of their orgasm experience, and also no correlation between higher testosterone levels and greater sexual assertiveness in either sex.[34]

If you’re not lifting super-heavy weights, doing high-intensity workouts, or eating a mainly vegan or vegetarian diet, your body probably makes as much creatine as it needs. “Creatine is naturally found in animal-based products,” says Bates, “so your body can make plenty of creatine as long as you have a balanced diet that includes animal-based products.” Protein sources like beef, chicken, pork, and fish help your body produce the creatine it needs — it varies depending on the source, but, in general, a 3-ounce serving of meat will have about 0.4 grams (g) of creatine, Bates says. (6)

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).
Supplementation of a loading phase of creatine has been noted to augment the increase in RBC levels of superoxide dismutase (SOD) from exercise, when measured immediately after, by 8.1%, but control groups increased to match within an hour.[299] Glutathione (normally decreases with exercise) and catalase (increases) were both unaffected,[299] and elsewhere in vitro red blood cells incubated with 3mM of creatine (within the supplemental range) is able to improve filterability (a measure of cell rheology, or fluid structure of the cell[300]) when RBC creatine was increased by 12.3% to reach 554µM.[301] This was thought to be due to reduced oxidative stress (assessed via MDA) in the red blood cells, which in the presence of 1-5mM creatine was progressively reduced by 20-41%.[301]
Myotonic Dystrophy type I (DM1) is an inhereted muscular disorder caused by an expanded CTG repeat in the DMPK gene on chromosome 19q13.3 (genetic cause of the disorder[561]) resulting in muscular degeneration and myotonia. The related myopathy, Myotonic Dystrophy type II (DM2) which is also known as proximal myotonic myopathy (PROMM) is due to a CCTG repeat on 3q,[562] and is less affected by myotonia and more by muscular pain and weakness. There is no cure for either because they are genetic disorders, so current therapies are aimed at reducing side-effects. Therapies include modafinil for the somnolence[563] and perhaps creatine for the reduction in strength and functionality.[548]
1. Are you tracking calories? Doesn't have to be religiously but one should have a general idea of where they're at if the goal is mass gain and things have stalled. I'm not talking about weighing every gram of food you put in your mouth and meticulously logging your life on MyFitnessPal. As long as you're aware (within 100-200 calories) of what's going in, you should have an idea of what to adjust.
Safety. Iron overload may cause a disease called hemochromatosis in some susceptible people. Iron supplements should only be prescribed by a doctor, and for athletes or those who train heavily, a sports physician combined with a sports dietitian may be preferable. Be sure to take care with this because iron supplements should not be taken casually. Iron supplements may cause constipation and gastric upset in some people.
Firstly, let’s establish where your glutes are and what they actually refer to! Your ‘glutes’ — or your gluteal muscles, as they are more formally known — refer to the muscles in your butt. Specifically, there are three major muscles in this area: your gluteus maximus (the main, large muscle that shapes your backside), your gluteus medius and your gluteus minimus (two smaller muscles that assist the gluteus maximus in moving your body).
Creatine is only taken up by its transporter, and changes in the activity level of this transporter are wholly causative of changes in creatine uptake. The transporter is regulated by mostly cytosolic factors as well as some external factors that affect creatine transport activity, [143] including extracellular creatine.[140] Agents affecting creatine transport are further divided into positive regulators (those that increase activity of the transporter) and negative regulators (those that suppress activity).
When it comes to supplementation though, nitric oxide boosters still have a way to go. The body has a limit on how much L-arginine it absorbs. L-citrulline itself is converted to L-arginine in your body, and thus hits the rate limit again. Thus, neither supplement is reliable at increasing the concentration of nitric oxide in the blood. Agmatine is mostly untested on people, with no evidence for its muscle building effects. Manipulating nitric oxide levels may be a good way to build muscle, but the supplements currently on the market won’t help.
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] 
There have been a few reported renal health disorders associated with creatine supplementation [73,74]. These are isolated reports in which recommended dosages are not followed or there is a history of previous health complaints, such as renal disease or those taking nephrotoxic medication aggravated by creatine supplementation [73]. Specific studies into creatine supplementation, renal function and/or safety conclude that although creatine does slightly raise creatinine levels there is no progressive effect to cause negative consequences to renal function and health in already healthy individuals when proper dosage recommendations are followed [73-77]. Urinary methylamine and formaldehyde have been shown to increase due to creatine supplementation of 20 g/d; this however did not bring the production outside of normal healthy range and did not impact on kidney function [56,78]. It has been advised that further research be carried out into the effects of creatine supplementation and health in the elderly and adolescent [73,75]. More recently, a randomized, double blind, 6 month resistance exercise and supplementation intervention [79] was performed on elderly men and women (age >65 years) in which subjects were assigned to either a supplement or placebo group. The supplement group was given 5 g CM, 2 g dextrose and 6 g conjugated linoleic acid/d, whilst the placebo group consumed 7 g dextrose and 6 g safflower oil/d. CM administration showed significantly greater effects to improve muscular endurance, isokinetic knee extension strength, fat free mass and to reduce fat mass compared to placebo. Furthermore the supplement group had an increase in serum creatinine but not creatinine clearance suggesting no negative effect on renal function.

Creatine synthesis primarily occurs in the liver and kidneys.[2][16] On average, it is produced endogenously at an estimated rate of about 8.3 mmol or 1 gram per day in young adults.[16][17] Creatine is also obtained through the diet at a rate of about 1 gram per day from an omnivorous diet.[16][18] Most of the human body's total creatine and phosphocreatine stores are found in skeletal muscle, while the remainder is distributed in the blood, brain, and other tissues.[17][18]
Medicines used for treating depression are called antidepressants and may be categorized into several classes. Some of these drugs include tricyclic antidepressants such as Nortriptyline and Imipramine, Selective serotonin reuptake inhibitors (SSRIs) including Fluoxetine, Citalopram, and Sertraline, and Selective Norepinephrine Reuptake Inhibitors (SNRIs) including Venlafaxine and Duloxetine. These drugs, generally, act by increasing the amounts of chemical substances that stimulate the brain. Each class of antidepressants has a different safety profile and side effects, so, ensure you consult your doctor for a prescription and dosage recommendations.
However, protein isn’t everything. Contrary to popular belief, carbohydrates and calories from fats are also important. To gain muscle, people who are slender or scrawny need to create a calorie surplus in order to bulk up. That means you need proteins and plenty of healthy carbs, vegetables and even some fats (think healthy fats like nuts, avocado, olive oil, etc.). Carbohydrates play a key role in building muscle. This macronutrient has gotten a bad rap for making people fat. However, if you work out properly, eating plenty of carbs is in your best interest. After training, it’s ideal to ingest some carbs in combination with protein to help replenish your muscles’ glycogen stores.
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]
Men appear to have higher active creatine-kinase systems, and racial differences favor black people over hispanic people over white people in terms of the activity of the creatine-kinase system. This system is more variable in men, independent of supplementation. Exercise may increase the activity of the creatine-kinase system independent of supplementation.
Casein, the source of the white color of milk, accounts for 70-80% of milk protein. Casein exists in what’s known as a micelle, a compound similar to a soap sud which has a water-averse inside and water-loving outside. This property allows the protein to provide a sustained, slow release of amino acids into the blood stream, sometimes lasting for hours. This makes casein a good protein source immediately before a workout to provide a continual amino acid supply to the muscles. Some studies suggest that combined supplementation with casein and whey offers the greatest muscular strength improvement (Kerksick, 2006).
However, caffeine does not negate the benefits of creatine loading when not coingested, but just taken before exercise in the same dosage.[593] This result indicates that loading creatine without caffeine on a daily basis, but saving caffeine for select workouts, may be an effective strategy, as creatine does not adversely affect caffeine’s ergogenic effects[593][594] and may enhance creatine’s effectiveness in anaerobic exertion if the two compounds are alternated.[595]
Green tea offers many health benefits, such as inhibition of cardiovascular disease and cancer. It also has some mild thermogenic effects, independent of its caffeine content, that may assist fat loss. Some studies even show that green tea offers protection against joint degeneration. If you don't have the time or inclination to drink several cups of green tea daily, you can get the same or better effects by using standardized capsules or tablets of green tea.
The creatine kinase system appears to be detectable in endothelial cells.[314][315] Under basal conditions, creatine itself is expressed at around 2.85+/-0.62μM[316] (three-fold higher than HUVEC cells[314]). When incubating the medium with 0.5mM creatine, endothelial cells can take up creatine via the creatine transporter (SLC6A8) and increase both creatine (almost doubling) and phosphocreatine (nearly 2.5-fold) concentrations.[316]
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Lie on your left side and position yourself so that your bottom forearm is directly under your armpit and your legs are straight with feet stacked. Brace your core and lift your hips in the air, forming a straight line from ankles to shoulders. Next, raise your top leg, without bending your knee, a few inches into the air. Hold for 3-5 seconds, lower the leg, and repeat. Complete required reps then switch sides.
Compound exercises work several muscle groups at once, and include movement around two or more joints. For example, in the leg press, movement occurs around the hip, knee and ankle joints. This exercise is primarily used to develop the quadriceps, but it also involves the hamstrings, glutes and calves. Compound exercises are generally similar to the ways that people naturally push, pull and lift objects, whereas isolation exercises often feel a little unnatural.
This ingredient also plays a major role in cell growth, recovery, and communication. Increasing the amount of creatine stored in your muscles can speed up the growth of new muscle and help prevent current muscles from being degraded during exercise. By reducing muscle breakdown, creatine can speed up the healing and recovery processes, as there will be less damage to repair.

This is one of the most controversial recommendations I make, but it shouldn’t be. It’s no different than using thyroid medication. If your levels are low, and the other techniques here don’t work, use TRT. You will like your life again. If your levels are low, bioidentical testosterone will make you live longer and better, provided you use it right.

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]
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.
Even if you have a schedule that allows for a 5-day workout split, many people (I’d even call it the majority) simply don’t have the recovery capacity needed to make that work. This could be due to genetics, age, injury history, various lifestyle factors (sleep, stress, etc.) and more. In these cases, better results would be seen with 3-4 workouts per week instead.
The effect excess testosterone has on the body depends on both age and sex. It is unlikely that adult men will develop a disorder in which they produce too much testosterone and it is often difficult to spot that an adult male has too much testosterone. More obviously, young children with too much testosterone may enter a false growth spurt and show signs of early puberty and young girls may experience abnormal changes to their genitalia. In both males and females, too much testosterone can lead to precocious puberty and result in infertility. 

Trouble walking, running or doing other activities — Any physical movement that involves stability, flexibility and strength in the legs and hips can be compromised. For example, yoga, dancing, horseback riding, cycling, hiking, burst training, sprinting, plyometrics or tabata workouts, and other activities will be more difficult with underdeveloped glutes.