The creatine transporter is a sodium[139][140] and chloride[141][142] dependent membrane-associated transporter that belongs to the Na+/Cl-dependent family of neurotransmitter transporters.[143] In muscle cells and most other cell types,[131][141] the isomer of the creatine transporter is known as SLC6A8 (solute carrier family 6, member 8). SLC6A8 is encoded by the gene present on the Xq28 region of the human X-chromosome and is expressed in most tissues.[144] A related gene encoding a creatine transporter variant has also been identified at 16p11.1 that is expressed exclusively in the testes.[145] These two transporters share 98% homology.[144][145]

One limitation of many free weight exercises and exercise machines is that the muscle is working maximally against gravity during only a small portion of the lift. Some exercise-specific machines feature an oval cam (first introduced by Nautilus) which varies the resistance, so that the resistance, and the muscle force required, remains constant throughout the full range of motion of the exercise.
If you have been diagnosed with a certain testosterone deficiency, ask your doctor and/or pharmacist to see if TestoFuel could be beneficial for you. Aside from balancing your testosterone, you may experience increased muscle strength while using this supplement during your intense exercise routine. Here are certain instances where TestoFuel could help correct your testosterone problems:
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 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.
The important role of nutrition in building muscle and losing fat means bodybuilders may consume a wide variety of dietary supplements.[41] Various products are used in an attempt to augment muscle size, increase the rate of fat loss, improve joint health, increase natural testosterone production, enhance training performance and prevent potential nutrient deficiencies.
Carbohydrates play an important role for bodybuilders. They give the body energy to deal with the rigors of training and recovery. Carbohydrates also promote secretion of insulin, a hormone enabling cells to get the glucose they need. Insulin also carries amino acids into cells and promotes protein synthesis.[26] Insulin has steroid-like effects in terms of muscle gains.[27] It is impossible to promote protein synthesis without the existence of insulin, which means that without ingesting carbohydrates or protein—which also induces the release of insulin—it is impossible to add muscle mass.[28] Bodybuilders seek out low-glycemic polysaccharides and other slowly digesting carbohydrates, which release energy in a more stable fashion than high-glycemic sugars and starches. This is important as high-glycemic carbohydrates cause a sharp insulin response, which places the body in a state where it is likely to store additional food energy as fat. However, bodybuilders frequently do ingest some quickly digesting sugars (often in form of pure dextrose or maltodextrin) just before, during, and/or just after a workout. This may help to replenish glycogen stored within the muscle, and to stimulate muscle protein synthesis.[29]

Higher percieved effort during heat (or due to elevations in body heat) are thought to be mediated by either the serotonergic system (suppresses performance)[388] or the dopaminergic system (enhances performance),[389][234] and creatine is thought to be involved in percieved effort during heat training since it has been noted previously to interact with neurotransmission by enhancing both serotonergic[253] and dopaminergic[230] neurotransmission.
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 most of these muscle building supplements can be taken at any time of the day, some are best to include in your pre-workout routine. Citrulline malate, in particular, is one that should be taken about an hour ahead of your workout. Because this supplement boosts performance, taking it ahead of your workout will maximize its effect, making sure you get the most out of the supplement.
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]
This suppression of creatine synthesis is thought to actually be beneficial, since creatine synthesis requires s-adenosyl methionine as a cofactor and may use up to 40-50% of SAMe for methylation[35][36][122] (initially thought to be above 70%, but this has since been re-evaluated[122]) though the expected preservation of SAMe may not occur with supplementation.[487] Reduced creatine synthesis, via preserving methyl groups and trimethylglycine (which would normally be used up to synthesize SAMe), is also thought to suppress homocysteine levels in serum,[37] but this may also not occur to a practical level following supplementation.[487]
One study in elite swimmers subject to sprints (varying in length from 25-100m) failed to find benefit with creatine supplementation, although there was also a failure on leg extension strength, suggesting nonresponse.[399] This has been noted twice elsewhere with a similar protocol,[400][401] while one study in elite swimmers subject to single 50m or 100m sprints found benefit with supplementation[402] and one found benefit with six repeated 50m sprints by 2%, yet not ten repeated 25m sprints with elite male swimmers (females failed to find benefit).[403] Another study also noted benefits in elite swimmers on a sprinting protocol.[156] Overall, the evidence is quite limited and suggests either a mild, or more likely, no increase for elite swimmers, although one study confirming an increase in body and water weight[401] failed to find a decrement in performance.
Chwalbinska-Monteta [34] observed a significant decrease in blood lactate accumulation when exercising at lower intensities as well as an increase in lactate threshold in elite male endurance rowers after consuming a short loading (5 days 20 g/d) CM protocol. However, the effects of creatine supplementation on endurance performance have been questioned by some studies. Graef et al [35] examined the effects of four weeks of creatine citrate supplementation and high-intensity interval training on cardio respiratory fitness. A greater increase of the ventilatory threshold was observed in the creatine group respect to placebo; however, oxygen consumption showed no significant differences between the groups. The total work presented no interaction and no main effect for time for any of the groups. Thompson et al [36] reported no effects of a 6 week 2 g CM/d in aerobic and anaerobic endurance performance in female swimmers. In addition, of the concern related to the dosage used in these studies, it could be possible that the potential benefits of creatine supplementation on endurance performance were more related to effects of anaerobic threshold localization.
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?
Extracellular creatine (creatine outside of a cell) appears to influence creatine uptake into a cell. It seems that prolonged and excessive levels of creatine actually suppress uptake (a form of negative regulation to prevent excessive influx).[180] In vitro studies in rat muscle cells have shown that including 1mM creatine into cell culture medium substantially reduces creatine uptake into cells. The inhibitory effect was partially negated by protein synthesis inhibitors, suggesting that high levels of creatine induce the expression of a protein that suppresses creatine transporter activity.[180] Similar findings were reported in a later study in cultured mouse myoblasts, which noted a 2.4-fold increase in intracellular creatine levels in the presence of the protein synthesis inhibitor cyclohexamide.[174]
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]
Three amino acids (glycine, arginine and methionine) and three enzymes (L-arginine:glycine amidinotransferase, guanidinoacetate methyltransferase and methionine adenosyltransferase) are required for creatine synthesis. The impact creatine synthesis has on glycine metabolism in adults is low, however the demand is more appreciable on the metabolism of arginine and methionine [11].
As I mentioned earlier, the exercises that come first in your workout (aka primary compound exercises) should usually be done in the 5-8 rep range. Exercises in the middle (aka your secondary compound exercises) should usually be done in the 8-10 rep range. Exercises done at the end of your workout (which is typically where isolation exercises belong) should usually be done in the 10-15 rep range.
In regard to the loading period, two reviews suggest that the range of weight gain associated with creatine supplementation at 20g for 7 days is in the range of 0.9-1.8kg (1.98-3.96lbs).[612][613] The highest reported increase in water weight associated with creatine loading, although measured a month after loading started (after a maintenance phase) was 3.8kg (8.36lbs).[614]
Beta-alanine is a naturally occurring non-essential amino acid that comes into the body through foods that are rich in protein. The performance-enhancing aspect of beta-alanine (BA) is due to its ability to increase intra-muscular levels of carnosine. Increasing beta-alanine through supplementation may raise carnosine levels by over 60 percent in as quickly as four weeks.[6]
Electrolytes derive mainly from minerals in the diet and they maintain fluid balance and assist the nervous system to perform muscle contractions. Electrolytes are sodium, potassium, magnesium, calcium and chloride, bicarbonate, phosphate, sulfate. Exercisers are particularly dependent on sodium and potassium balance. Carbohydrates are important for fueling exercise, including vigorous weight training, and in post-exercise energy replacement nutrition. Carbohydrates, mostly sugars, are formulated in sports drinks with electrolytes such as sodium chloride and potassium and sometimes magnesium.
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A: No. You should ensure that the squat and hinge motor pattern are both emphasized but other variations (front squat, sumo deadlift, safety bar squat, Romanian deadlift) should be included until you can master technique on the more advanced variations. For more information on exercise progressions and regressions see this article: Train Like An Athlete, Look Like a Bodybuilder.
Nitrate-rich foods like beets, radishes, and pomegranates are a great way to boost the production of nitric oxide (NO). Although there's very limited research examining the effects of beet root juice and pomegranate extract on resistance training, these ingredients have previously been shown to increase skeletal muscle blood flow and lead to reduced soreness, which may ultimately lead to improvements in strength and performance.[9,10]

One limitation of many free weight exercises and exercise machines is that the muscle is working maximally against gravity during only a small portion of the lift. Some exercise-specific machines feature an oval cam (first introduced by Nautilus) which varies the resistance, so that the resistance, and the muscle force required, remains constant throughout the full range of motion of the exercise.


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.
There is a nuclear receptor known as TIS1 (orphan receptor, since there are no known endogeouns targets at this time) which positively influences transcription of new creatine transporters[171] and, in C2C12 myotubes, seems to be responsive to cAMP or adenyl cyclase stimulation from forskolin (from Coleus Forskohlii) with peak activation at 20µM.[171][172] 
Creatine supplementation has been noted to improve general wellbeing and health status (assessed by St George’s Respiratory questionnaire[582]) of people with COPD over two weeks loading (17.1g daily with carbohydrates) and ten weeks of 5.7g maintenance.[579] The studies that failed to find improvements with creatine supplementation on muscular performance also failed to find improvements in this rating scale, relative to placebo.[580][581]
According to the two meta-analyses on the topic, creatine significantly increases power when supplemented in both sexes over a period of time up to 8 weeks, during which improvement over placebo is maintained, rather than being enhanced further. The rate at which power is derived from a resistance training regimen appears to be up to 78.5% greater with creatine relative to placebo, and in active trained men who are naive to creatine, this can be quantified at about 7kg for the bench press and 10kg for the squat over 8 weeks.
The first open label trial on ALS failed to significantly alter lung function as assessed by FEV (when comparing the rate of decline pretreatment relative to treatment).[545] Creatine has elsewhere failed to benefit lung function at 5g daily for months relative to control[546] and failed to significantly attenuate the rate of lung function deterioration over 16 months at 10g daily[505] and 5g daily over nine months.[507]
Progain contains an easily digested source of carbohydrate, providing much needed carbohydrate to fuel your workout before or after. By adding creatine to your diet, in a shake, in food or in capsules, is proven to increase strength, build muscle size and support training intensity. At Maximuscle we have a number of products with added creatine, such as: Creatine Monohydrate, Creatamax Capsules, Cyclone (powder & bars), Progain Flapjack.
Trimethylglycine (TMG, betaine) is a dietary supplement and component of beet root, which is a methyl donor. It contributes to metabolic processes in the body which require a methyl group either directly (the methylation of homocysteine) or indirectly via replenishing the active form of folate or via replenishing S-adenosyl methionine (SAMe). As the synthesis of creatine (via GAMT) requires a donation from SAMe,[597] it is thought that TMG can aid in creatine synthesis, which has been noted in the rat liver in the absence of creatine supplementation.[598]
Although creatine supplementation has been shown to be more effective on predominantly anaerobic intermittent exercise, there is some evidence of its positive effects on endurance activities. Branch [28] highlights that endurance activities lasting more than 150s rely on oxidative phosphorylation as primary energy system supplier. From this meta analysis [28], it would appear that the ergogenic potential for creatine supplementation on predominantly aerobic endurance exercise diminishes as the duration of the activity increases over 150s. However it is suggested that creatine supplementation may cause a change in substrate utilization during aerobic activity possibly leading to an increase in steady state endurance performance.
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.
The bulking and cutting strategy is effective because there is a well-established link between muscle hypertrophy and being in a state of positive energy balance.[19] A sustained period of caloric surplus will allow the athlete to gain more fat-free mass than they could otherwise gain under eucaloric conditions. Some gain in fat mass is expected, which athletes seek to oxidize in a cutting period while maintaining as much lean mass as possible.
You've figured out the exercises you should be doing, but what about the number of sets and repetitions? Your decision should be based on your goals. The American College of Sports Medicine recommends 4 to 6 reps for strength and hypertrophy, 8 to 12 reps for muscular strength and 10 to 15 reps for muscular endurance. They also recommend at least one set of each exercise to fatigue although you'll find that most people perform about 2 to 3 sets of each exercise. In general:
Another study demonstrated that females receiving 4 days of high-dose creatine intake (20 g/day) followed by low-dose creatine intake (5 g/day) during 10 weeks of resistance training (3hours/week) increased muscle PCr concentrations by 6%. Also, maximal strength of the muscle groups trained increased by 20-25%, maximal intermittent exercise capacity of the arm flexors increased by 10-25% and fat-free mass increased by 60% [11].
Having a spotter nearby is particularly important when using free weights. Even someone in great shape sometimes just can't make that last rep. It's no big deal if you're doing biceps curls; all you'll have to do is drop the weight onto the floor. But if you're in the middle of a bench press — a chest exercise where you're lying on a bench and pushing a loaded barbell away from your chest — it's easy to get hurt if you drop the weight. A spotter can keep you from dropping the barbell onto your chest.
If you’ve been training longer than 6–12 months, you can split your workouts into upper- and lower-body days. The most common setup is to train upper body one day and lower the next so that each area gets trained twice in one week. If you train four days per week, you can train upper body on Monday, lower Tuesday, rest Wednesday, and then do upper body again on Thursday, lower body on Friday, and then rest on the weekend.
Zinc is important to produce the male hormone testosterone and in building the immune system. Magnesium is an essential component of the nervous system and for maintaining heart health. Both have a range of important biochemical function. Zinc and magnesium are often marketed to bodybuilders in combination in a supplement called ZMA. Zinc is in whole grains, seeds, nuts and particularly meat and oysters. After years of research, no evidence exists to show that either mineral offers bodybuilding or athletic performance enhancement in excess of the recommended dietary requirements.

Children: Creatine is POSSIBLY SAFE in children when taken by mouth appropriately. Creatine 3-5 grams daily for 2-6 months has been taken safely in children 5-18 years of age. Creatine 2 grams daily for 6 months has been taken safely in children 2-5 years of age. Additionally, creatine 0.1-0.4 grams/kg daily for up to 6 months has been taken safely in both infants and children.
Reducing creatine synthesis by supplementing it has preliminary evidence supporting its ability to reduce homocysteine concentrations in the body, since the synthesis of creatine would normally produce some homocysteine as a byproduct. This may apply to a certain subset of people (MTHFR TT homozygotes, about 10% of North Americans) but at the moment there is not enough evidence to suggest that this occurs in all people supplementing creatine.
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.

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.

In vitro, creatine (0.125mM or higher) can reduce excitotoxicity from glutamate, which is thought to be secondary to preserving intracellular creatine phosphate levels.[209] Glutamate-induced excitotoxicity is caused by excessive intracellular calcium levels resulting from ATP depletion. Since high levels of calcium inside the cell are toxic, ATP preserves membrane integrity,[210] in part by promoting calcium homeostasis. When ATP is depleted, the sodium-potassium ATPase pump (Na+,K+-ATPase) stops working, leading to sodium accumulation in the cell. This reduces the activity of the sodium-calcium exchange pump, which, alongside a lack of ATP, reduces calcium efflux through the Na+,K+-ATPase. Thus, ATP depletion leads to intracellular calcium overload, loss of membrane potential, and excitotoxic cell death. Therefore, by helping preserve ATP levels, creatine is protective against excitotoxicity. This protective effect was noted after either creatine preloading or addition up to 2 hours after excitotoxicity.[209] Protection from glutamate-induced toxicity also extends to glial cells[211] and is additive with COX2 inhibition.[212]

Without supplementation, approximately 14.6mmol (2g) of creatinine, creatine’s urinary metabolite, is lost on a daily basis in a standard 70kg male ages 20-39. The value is slightly lower in females and the elderly due to a presence of less muscle mass.[35] This amount is considered necessary to obtain in either food or supplemental form to avoid creatine deficiency. Requirements may be increased in people with higher than normal lean mass.[35][198] Creatine excretion rates on a daily basis are correlated with muscle mass, and the value of 2g a day is derived from the aforementioned male population with about 120g creatine storage capacity.[35] Specifically, the rate of daily creatine losses is about 1.6%[199]-1.7%,[25] and mean losses for women are approximately 80% that of men due to less average lean mass.[35] For weight-matched elderly men (70kg, 70-79 years of age) the rate of loss of 7.8mmol/day,[49] or about half (53%) that of younger men.

The genealogy of lifting can be traced back to the beginning of recorded history[1] where humanity's fascination with physical abilities can be found among numerous ancient writings. In many prehistoric tribes, they would have a big rock they would try to lift, and the first one to lift it would inscribe their name into the stone. Such rocks have been found in Greek and Scottish castles.[2] Progressive resistance training dates back at least to Ancient Greece, when legend has it that wrestler Milo of Croton trained by carrying a newborn calf on his back every day until it was fully grown. Another Greek, the physician Galen, described strength training exercises using the halteres (an early form of dumbbell) in the 2nd century.
Beta-alanine is a naturally occurring non-essential amino acid that comes into the body through foods that are rich in protein. The performance-enhancing aspect of beta-alanine (BA) is due to its ability to increase intra-muscular levels of carnosine. Increasing beta-alanine through supplementation may raise carnosine levels by over 60 percent in as quickly as four weeks.[6]
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.
Researchers found that 5g of creatine four times daily for a week (loading) before sleep deprivation for 12-36 hours was able to preserve cognition during complex tasks of executive function at 36 hours only, without significant influence on immediate recall or mood.[279] A similar protocol replicated the failure to improve memory and attention, but noted less reports of fatigue (24 hours) and less decline of vigor (24 hours) although other mood parameters were not measured.[276]
These supplements can vary considerably from product to product in ingredients, serving sizes, and more. But the goal of each of them is generally quite similar. Most bodybuilding supplements are designed to help stimulate new muscle growth, cut away excess fat, and improve the recovery process so that you can get the most out of each trip to the gym.
Carducci, C., Birarelli, M., Leuzzi, V., Carducci, C., Battini, R., Cioni, G., and Antonozzi, I. Guanidinoacetate and creatine plus creatinine assessment in physiologic fluids: an effective diagnostic tool for the biochemical diagnosis of arginine:glycine amidinotransferase and guanidinoacetate methyltransferase deficiencies. Clin Chem 2002;48(10):1772-1778. View abstract.
I learned from this to focus on the body weight exercises. I never understood why I could lift a lot of weight, but felt weak when it came to dips, pull ups, push ups etc. Normally I spend 2 hours in a gym: 20 min jogging, 80 min lifting, 20 min jogging, 5 days a week. After reading this I’m excited to incorporate HIIT training in addition to mobility training on my off days, because I think I was wasting a lot of time and effort. I can push way harder on lifting days without the jog beforehand, so I’ll also be able to make the most of 60 minutes…
Many non-competitive bodybuilders choose not to adopt this conventional strategy, as it often results in significant unwanted fat gain during the "bulking" phase. The attempt to increase muscle mass in one's body without any gain in fat is called clean bulking. Competitive bodybuilders focus their efforts to achieve a peak appearance during a brief "competition season".[citation needed] Clean bulking takes longer and is a more refined approach to achieving the body fat and muscle mass percentage a person is looking for. A common tactic for keeping fat low and muscle mass high would be to have higher calorie and lower calorie days to maintain a balance between gain and loss. Many clean bulk diets start off with a moderate amount of carbs, moderate amount of protein, and a decently low amount of fats. "Gaining lean muscle means going for leaner cuts of meat, like flank steaks and fillets, chicken, and, of course, fish," says White[who?]. "Enjoy your meat with some starch: rice, beans, quinoa, whole-grain couscous, or sweet potato, for example".[20] To maintain a clean bulk it is important to reach calorie goals every day. Macronutrient goals will be different for each person, but, it is ideal to get as close as possible.
Yes, genetically some of us put on muscle faster than others, but even then it’s fractions of a degree, not DRASTIC sweeping differences. We tend to get this question from men or women who are so thin and have such fast metabolisms, they probably need to put on 40-50+ pounds of both fat and muscle, before they would ever even think to use the word “too bulky.”
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].
Peirano, R. I., Achterberg, V., Dusing, H. J., Akhiani, M., Koop, U., Jaspers, S., Kruger, A., Schwengler, H., Hamann, T., Wenck, H., Stab, F., Gallinat, S., and Blatt, T. Dermal penetration of creatine from a face-care formulation containing creatine, guarana and glycerol is linked to effective antiwrinkle and antisagging efficacy in male subjects. J.Cosmet.Dermatol. 2011;10(4):273-281. View abstract.
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] 
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