Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.[26] Clinically, there are three distinct disorders of creatine metabolism. Deficiencies in the two synthesis enzymes can cause L-arginine:glycine amidinotransferase deficiency caused by variants in GATM and guanidinoacetate methyltransferase deficiency, caused by variants in GAMT. Both biosynthetic defects are inherited in an autosomal recessive manner. A third defect, creatine transporter defect, is caused by mutations in SLC6A8 and inherited in a X-linked manner. This condition is related to the transport of creatine into the brain.[27]
When it comes to building muscle, there are numerous theories, methods, and preferences. Whether the goal is improved health, aesthetics, performance, or a combination of all three, there is no shortage of advice to help you get there. So much so that it can sometimes become overly complicated and you forget about the basic facts. But, it’s simpler than it seems.
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.

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.
In a mouse model of allergin-induced asthma, where mice were sensitized by ovalbumin for three weeks and then given 500mg/kg creatine, supplementation induced an increase in asthmatic hyperresponsiveness to low but not high doses of methacholine.[440] This hyperresponsiveness was associated with increased eosinophil and neutrophil infiltration into the lungs, and an increase in Th2 cell cytokines (IL-4 and IL-5) alongside an increase in IGF-1,[440] which is known to influence this process.[441] Interestingly, there was a nonsignificant increase in responsiveness in mice not sensitized to ovalbumin.[440]
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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.

In regard to liver fat buildup (steatosis), which is normally associated with reduced availability of S-adenosyl methionine[495][496] and a suppression in expression of genes involved in fatty acid oxidation (PPARα and CPT1), creatine supplementation at 1% of the rat diet alongside a diet that induces fatty liver is able to fully prevent (and nonsignificantly reduce relative to the control given standard diets) the aforementioned changes and the state of steatosis, as well as changes in serum biomarkers (glucose and insulin) that accompany steatosis.[125]  

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.

In addition to adequate protein, you need more calories (your protein intake contributes to your total caloric intake, so these two go hand in hand). Use the following formula to calculate the number you need to take in daily to gain one pound a week, and break down your diet using the macro guidelines listed above. (Give yourself two weeks for results to show up on the scale. If you haven't gained by then, increase your calories by 500 a day.)


Beast Creature could be another good option for female athletes. It’s tasty, it contains five types of creatine, and it contains ingredients that could improve fat loss by increasing insulin sensitivity. One potential bonus is that it also has 70 percent of your daily biotin, a nutrient often included in women’s multivitamins due its purported benefits for hair and nails.
While training intensity can be accomplished trough a targeted training program and an ability to adequately stimulate our muscles is something the motivated and determined bodybuilder often has no problem doing, muscle recovery is another issue. It is especially important at a time of the year when social demands and incorrect eating combine to stifle our progress.
If you're 12 weeks out from a competition, you want to maintain as much muscle as possible while torching fat from every angle. This means low-intensity cardio – high intensity cardio speeds up your metabolism and burns fat very quickly, so you run the risk of burning muscle too, Terry says – either first thing in the morning on an empty stomach, or immediately after your weights session, once you’ve depleted those glycogen levels.
Creatine is known to increase skeletal muscle cellular volume alongside increases in water weight gain.[346] Since glycogen itself also increases the osmolytic balance of a cell (draws in water)[347][348] and preliminary evidence shows a strong trend of creatine augmenting glycogen loading,[153] creatine is thought to be related to an increase in cell volume, which is known to promote glycogen synthesis.[112]
Naturo Nitro Creatine Chrome could be an interesting choice for women. It’s actually magnesium creatine chelate, a type of creatine that may help to improve performance without increasing water weight. We don’t have a lot of studies on it just yet, but the research we do have suggests it could potentially be a good choice for women who want to improve performance without experiencing the “bloat” of regular creatine.
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.
Creatine supplementation often causes weight gain that can be mistaken for increase in muscle mass. Increasing intracellular creatine may cause an osmotic influx of water into the cell because creatine is an osmotically active substance [10]. It is possible that the weight gained is water retention and not increased muscle. The retention of water may be connected to reports of muscle cramps, dehydration, and heat intolerance when taking creatine supplements. It would be prudent to encourage proper hydration for creatine users. Further research is needed to investigate these and other possible side effects.
Contrast loading is the alternation of heavy and light loads. Considered as sets, the heavy load is performed at about 85-95% 1 repetition max; the light load should be considerably lighter at about 30-60% 1RM. Both sets should be performed fast with the lighter set being performed as fast as possible. The joints should not be locked as this inhibits muscle fibre recruitment and reduces the speed at which the exercise can be performed. The lighter set may be a loaded plyometric exercise such as loaded squat jumps or jumps with a trap bar.

Jason Ferruggia is a highly sought after, world renowned strength & conditioning specialist and muscle building expert. Over the last 17 years he has personally trained more than 700 athletes from over 90 different NCAA, NFL, NHL and MLB organizations. He has also worked extensively with firefighters, police officers, military personnel, Hollywood stars and entertainers. Most importantly, Jason has helped over 53,000 skinny guys and hard gainers in 126 different countries build muscle and gain weight faster than they every thought possible.
^ "Popular sports supplements contain meth-like compound". USA Today. October 25, 2013. Cohen said researchers informed the FDA in May about finding the new chemical compound in Craze. The team found the compound — N,alpha-diethylphenylethylamine — has a structure similar to methamphetamine, a powerful, highly addictive, illegal stimulant drug. They believe the new compound is likely less potent than methamphetamine but greater than ephedrine.

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.

Carbohydrates provide quick energy in an anaerobic environment (high-intensity exercise), while fats provide sustained energy during periods of high oxygen availability (low-intensity exercise or rest). The breakdown of carbohydrates, fats, and ketones produces ATP (adenosine triphosphate). When cells use ATP for energy, this molecule is converted into adenosine diphosphate (ADP) and adenosine monophosphate (AMP). Creatine exists in cells to donate a phosphate group (energy) to ADP, turning this molecule back into ATP.[20][21][22][23]


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]
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.
3) Relatively low cholesterol. This is one nutrition category that many people overlook with these supplements, but it's arguable one of the most important. Remember, if you're going to be downing 2 of these a day, you DON'T want to be maxing out your cholesterol intake. Luckily, this whey keeps it down to 30mg per scoop (which is about 10% of your daily intake). I've seen worse and ... full review
A: The literature supports roughly 0.8-1 gram per pound of bodyweight in young adults. Can you eat more? As long as you have healthy, functioning kidneys, yes. Will you receive any further physiological benefit from it? Most likely, no. Not only that, since our calories are set, if we choose to overconsume protein then we must reduce either carbohydrates and/or fat in order to keep caloric expenditure within our set range. Once protein needs are met (~0.8-1g/lb of bodyweight) you will likely see greater benefits from higher carbohydrate consumptions given the influence they have on anabolism and the anaerobic energy pathway. However, as I mentioned above, these recommendations will differ for older trainees given the blunted anabolic response from the ingestion of amino acids. 
Kornblum, C., Schroder, R., Muller, K., Vorgerd, M., Eggers, J., Bogdanow, M., Papassotiropoulos, A., Fabian, K., Klockgether, T., and Zange, J. Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover study. Eur J Neurol 2005;12(4):300-309. View abstract.

Although creatine can be bought commercially as a standalone product it is often found in combination with other nutrients. A prime example is the combination of creatine with carbohydrate or protein and carbohydrate for augmenting creatine muscle retention [5] mediated through an insulin response from the pancreas [69]. Steenge et al [70] found that body creatine retention of 5 g CM was increased by 25% with the addition of 50 g of protein and 47 g of carbohydrate or 96 g carbohydrate when compared to a placebo treatment of 5 g carbohydrate. The addition of 10g of creatine to 75 g of dextrose, 2 g of taurine, vitamins and minerals, induced a change in cellular osmolarity which in addition to the expected increase in body mass, seems to produce an up regulation of large scale gene expression (mRNA content of genes and protein content of kinases involved in osmosensing and signal transduction, cytoskeleton remodelling, protein and glycogen synthesis regulation, satellite cell proliferation and differentiation, DNA replication and repair, RNA transcription control, and cell survival) [25]. Similar findings have also been reported for creatine monohydrate supplementation alone when combined with resistance training [71].
Gains will differ from one individual to another depending on body size and level of experience in the gym. To make sure you'’re gaining muscle, not fat, don'’t just consider your scale weight. Instead, rely on what you see in the mirror and use a tape measure twice a month to keep track of your waist and hips (you don't want to gain there)— as well as your biceps, chest and quads. Also, don'’t think that you have to gain a set amount of weight each and every week. "Your mass gain doesn'’t have to be uniform,"” Aceto explains. That means you can gain 1/2 pound one week and 1 1/2 the next, perhaps none the third week and still remain on course. "“Expecting uniform gains ignores the intricate makeup of the body and the way it gains mass -— or loses fat - which is by no means in linear fashion," adds Aceto.

Tough workouts drive muscle growth, but they generally cause a lot of damage to your muscles to do so. This damage often results in soreness for several days, which can make it tough to get to the gym or sometimes even move. Many bodybuilding supplements contain ingredients that work to reduce the breakdown of muscle during workouts, making the recovery process easier on the body.
If you're a serious strength or physique athlete, you've surely heard that supplements can help you get the most from your intense training sessions and on-point diet. But which supplements? The market is overstuffed like a bodybuilder in a child's blazer! You might be tempted to wander through a digital forest of get-big blogs and personal guru websites, but unfortunately those places can often be rife with misinformation.
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.
Creatine supplementation has once been noted to improve wellbeing and fatigue resistance in people with DM2, but has twice failed for people with DM1. In all three studies, it has failed to improve power output. This is thought to be due to a reduction in the expression of the creatine transporter preventing an increase in muscular phosphocreatine content.
If there are any benefits for swimming performance from creatine supplementation, they appear to be limited to a 50 meter sprint or a handful of 50 meter sprints with short intermissions. Excessive sprinting (over six sprints with short breaks) or too long of a break (five minutes rather than two) seem to not be associated with the benefits of creatine supplementation.
The failure of creatine to improve physical performance in these conditions is thought to be related to the myopathies in general, which are known to result in less phosphocreatine in skeletal muscle,[568] associated with reduced expression of the creatine transporter.[569] As creatine has once been noted to not accumulate in the skeletal muscle of people with DM1 given supplementation,[566] it is thought that the subjects did not respond to therapy.

There are several different available forms of creatine: creatine anhydrous which is creatine with the water molecule removed in order to increase the concentration of creatine to a greater amount than that found in CM. Creatine has been manufactured in salt form: creatine pyruvate, creatine citrate, creatine malate, creatine phosphate, magnesium creatine, creatine oroate, Kre Alkalyn (creatine with baking soda). Creatine can also be manufactured in an ester form. Creatine ethyl ester (hydrochloride) is an example of this, as is creatine gluconate which is creatine bound to glucose. Another form is creatine effervescent which is creatine citrate or CM with citric acid and bicarbonate. The citric acid and bicarbonate react to produce an effervescent effect. When mixed with water the creatine separates from its carrier leaving a neutrally charged creatine, allowing it to dissolve to a higher degree in water. Manufacturers claim that creatine effervescent has a longer and more stable life in solution. When di-creatine citrate effervescent was studied [59] for stability in solution it was found that the di-creatine citrate dissociates to citric acid and creatine in aqueous solutions which in turn forms CM and eventually crystallises out of the solution due to its low solubility. Some of the creatine may also convert to creatinine.
This concept of timing has been applied to everything from fat burners, protein supplements, carbohydrates, and various other supplements. In some cases, you can see a difference based on when you take a product. But more often, the timing is based more on anecdotal evidence than any hard science. Recently, this nutrient timing aspect has even been extended to creatine, a product that is so effective that it’s worth the investigation of determining if there’s an element that can give you even greater benefits.
The general sentiment among nutrition experts is that creatine monohydrate is, for most people, the best bet. It’s the cheapest form and more importantly, it’s the most well-researched. Hundreds of studies have been performed on creatine monohydrate and there’s no evidence of ill effects, whereas many of the more novel forms of creatine have one or sometimes no studies supporting them.
After your standard whey protein powder, creatine may be the most popular sports supplement on Earth, and with good reason. A lot of supplements out there have a few promising studies suggesting they may improve some aspect of performance. Creatine has hundreds of them, and study after study has shown that among most people (a small percentage of are non-responders) it can have a significant effect on several areas of performance. 

GLUTs are vesicle transporters that are the rate-limiting steps for bringing glucose into a cell, and GLUT4 is the most active variant.[327] Agents that reduce blood glucose (insulin or AMPK) are known to act via mobilizing GLUT4, and increased GLUT4 expression and activity is indicative of a greater ability to bring glucose into a cell, while reducing it impairs glucose uptake.[328] Rat studies have confirmed that creatine feeding increases muscular GLUT4 expression associated with increased insulin-stimulated glucose uptake.[329]
Using too much weight, too soon; always start lower than your expected ability and work your way up that first workout. If your form suffers, you are swinging the weight, or using momentum, this indicates you may be using too much weight. Greater momentum increases the potential for injury and reduces the effectiveness to the muscle group being targeted.
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