The synthesis of creatine (from guanidinoacetate via GAMT) also requires SAMe as a cofactor and is implicated in homocysteine production. While supplementation of guanidinoacetate at 0.36% (prior to SAMe) can increase homocysteine by up to 50% in rats, supplementation of creatine (0.4%) is able to suppress homocysteine by up to 25%, secondary to reducing creatine synthesis,[309] and has been replicated elsewhere with 2% of the rat diet, while a loading phase did not alter the benefits.[124]
Professor Marcos FrankToday, important stuff happened to you. Tonight, when you sleep, your brain will extend the process of turning that stimulation – the sites, sounds, thoughts, emotions, facts, etc. – into memories that you can access at a moments notice in the future. It’s amazing when you think about it: experiences, facts, skills, and even thought patterns become a part of who we are. How much do you know now that you didn’t know 1o to 15 years ago, or even last week, last month, or yesterday? The process of accumulating information, and accessing when needed, is so routine it’s easy to forget that something is going to make it possible. As it turns out, sleep plays a vital role in the formation of certain types of memories. In this interview, I speak with someone who has made, and continues to make, significant contributions to help the world better understand how all this magic works. My guest is Marcos Frank, Ph.D., who is the Interim Chair of the Department of Biomedical Sciences in the Elson S. Floyd College of Medicine at Washington State University. I hope you enjoy this discussion as much as I did.
A meta-analysis of 16 studies conducted on creatine and its influence on power and strength,[368][369] (with or without exercise in all age groups above 16, but placebo controlled and without crossover[368]) compiled studies utilizing a 5-7 day loading period with continued maintenance thereafter and studies assessing 1-3 rep bench press strength in trained young men. Seven studies (four of which are online[370][371][372][373]) totaling 70 people using creatine and 73 people in placebo showed a 6.85kg increase in strength relative to placebo, the benefits of which peaked at 8 weeks.[368] This meta-analysis also quantified a significant increase in squat strength (9.76kg) yet failed to find a significant influence on peak bicep contraction power, which may have been influenced by the two null studies[374][375] being in elderly people while the positive study[376] was statistically outweighed, but noted an 1.8-fold increase in power associated with creatine over placebo. The other meta-analysis conducted the following year[369] calculated effect sizes for creatine supplementation and noted no significant differences between genders or when comparing trained and untrained individuals. The mean effect size of exercises lasting below 30s (those that use the creatine-phosphate system) was 0.24+/-0.02 and performed significantly better than placebo, where exercise increased performance by 4.2+/-0.6% while the addition of creatine enhanced this effect to 7.5+/-0.7%.[369]
To succeed and thrive as a bodybuilder, it takes more than overwhelming muscular strength or athletic prowess. Judges select bodybuilding champions based on muscle mass, definition, proportion, symmetry, and an athlete’s stage presence. Given the criteria, it is no surprise that most serious bodybuilders consider supplementation to be an essential component of their training regimen.

A commercially available pre-workout formula comprised of 2.05 g of caffeine, taurine and glucuronolactone, 7.9 g of L-leucine, L-valine, L-arginine and L-glutamine, 5 g of di-creatine citrate and 2.5 g of β-alanine mixed with 500 ml of water taken 10 minutes prior to exercise has been shown to enhance time to exhaustion during moderate intensity endurance exercise and to increase feelings of focus, energy and reduce subjective feelings of fatigue before and during endurance exercise due to a synergistic effect of the before mentioned ingredients [72]. The role of creatine in this formulation is to provide a neuroprotective function by enhancing the energy metabolism in the brain tissue, promoting antioxidant activities, improving cerebral vasculation and protecting the brain from hyperosmotic shock by acting as a brain cell osmolyte. Creatine can provide other neuroprotective benefits through stabilisation of mitochondrial membranes, stimulation of glutamate uptake into synaptic vesicles and balance of intracellular calcium homeostasis [72].


Standing with your feet hips distance apart, hold a barbell or free weights at shoulder height (either the barbell resting above your shoulder blades on your back, or free weights resting on top of your shoulder muscles held in front of you). Keeping your spine in a neutral position move into the squat by retracting your hips and pulling them backward. Hinging at your hips, bend your knees until your thighs come almost parallel to the ground (knees should be directly over your feet). Then push back up until your back is straight and repeat 5–10 times depending on the weight you’re using.


In another case, supplements touted as "myostatin blockers" were formulated from a type of sea algae. In a test tube, they effectively blocked the activity of the protein myostatin, which inhibits muscular growth in the body. The supplement ads implied that they'd enable you to develop unprecedented levels of muscular growth, but as it turned out, they didn't actually work in the human body.
Some of these medications that can harm the kidneys include cyclosporine (Neoral, Sandimmune); aminoglycosides including amikacin (Amikin), gentamicin (Garamycin, Gentak, others), and tobramycin (Nebcin, others); nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen (Advil, Motrin, Nuprin, others), indomethacin (Indocin), naproxen (Aleve, Anaprox, Naprelan, Naprosyn), piroxicam (Feldene); and numerous others.

Discomfort can arise from other factors. Individuals who perform large numbers of repetitions, sets, and exercises for each muscle group may experience a burning sensation in their muscles. These individuals may also experience a swelling sensation in their muscles from increased blood flow (the "pump"). True muscle fatigue is experienced as a marked and uncontrollable loss of strength in a muscle, arising from the nervous system (motor unit) rather than from the muscle fibers themselves. Extreme neural fatigue can be experienced as temporary muscle failure. Some weight training programs, such as Metabolic Resistance Training, actively seek temporary muscle failure; evidence to support this type of training is mixed at best.[24] Irrespective of their program, however, most athletes engaged in high-intensity weight training will experience muscle failure during their regimens.


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.
The amount of testosterone synthesized is regulated by the hypothalamic–pituitary–testicular axis (see figure to the right).[133] When testosterone levels are low, gonadotropin-releasing hormone (GnRH) is released by the hypothalamus, which in turn stimulates the pituitary gland to release FSH and LH. These latter two hormones stimulate the testis to synthesize testosterone. Finally, increasing levels of testosterone through a negative feedback loop act on the hypothalamus and pituitary to inhibit the release of GnRH and FSH/LH, respectively.
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]
Spillane M, Schoch R, Cooke M, Harvey T, Greenwood M, Kreider R, Willoughby DS. The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels. J Int Soc Sports Nutr. 2009;6:6. doi: 10.1186/1550-2783-6-6. [PMC free article] [PubMed] [CrossRef]
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]
As we all adjust to the time change, it’s worthwhile to consider how other aspects of our lives can sway our circadian rhythms. Circadian clocks govern the rhythms of sleep and activity in virtually all animals and are responsive to a variety of stimuli like light and stress. Research is starting to suggest that our eating patterns – specifically when we eat – can also have a pervasive impact.
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.

I can’t predict what sort of results you’ll see in that first year, but it can be pretty epic if you attack it right! Muscle growth might happen slower than you want, but I expect something different will happen along the way – you’ll fall in love with this idea of building STRENGTH! In fact, getting hooked on progress, and strength training is one of the best things you can do for yourself.


However, a much more accurate determination of how much fluid is necessary can be made by performing appropriate weight measurements before and after a typical exercise session, to determine how much fluid is lost during the workout. The greatest source of fluid loss during exercise is through perspiration, but as long as your fluid intake is roughly equivalent to your rate of perspiration, hydration levels will be maintained.[14]
Creatine supplementation at 300mg/kg for one week (loading with no maintenance) in youth subject to six repeated 35m sprints (10s rest, known as the Running-based Anaerobic Sprint Test or RAST) noted that the increased average and peak power output seen in creatine was not met with a reduction in fatigue, although there was an attenuation in inflammation from exercise (TNFα and CRP).[299]
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.
What happened was that, statistically speaking (less than 5% chance what was observed was due to chance means ‘significant’ for this study) there was no significant difference between pre- and post- workout, meaning that both were equally effective. This protocol did note that both groups found benefits with creatine supplementation, but they both found the same amount of benefit.
There appears to be some potential for creatine supplementation. However, many questions remain. Are there any long-term harmful effects from supplementation? Is there a point where enhanced performance levels off from long-term supplement usage? What effect does "stacking" or taking two ergogenic aids simultaneously have on the body? What happens if you immediately stop taking the creatine supplement? Is the enhanced performance great enough to warrant the expense of the supplement? Until further research answers these questions, creatine is not recommended for the average athlete.
This muscle-building, power-enhancing supplement has an extremely high safety profile and a plethora of evidence to support its efficacy. Creatine supplementation works by increasing the availability of creatine and phosphocreatine (PCr) within the muscle, helping to maintain energy during high-intensity exercise such as weightlifting. Furthermore, increasing the availability of PCr may help speed up recovery between sets.

Strong glutes also allow for movements such as bending over, squatting down, standing up straight, pushing off the ground (such as to run) and for maintaining other aspects related to proper posture. A 2005 report published in the Journal of Experimental Biology states that “The human gluteus maximus is a distinctive muscle in terms of size, anatomy and function compared to apes and other non-human primates …. Enlargement of the gluteus maximus was likely important in the evolution of hominid running capabilities.” (1)
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. 
Achy knees are often written off as an inevitable side effect of getting older. And while it’s true knee pain has many age-related causes (namely, arthritis), chances are weak glutes are a big part of the problem, Kline says. If you’ve been diagnosed with arthritis, strengthening your glutes can at least help offset some of the pain you might experience, she says.
In general, muscle content of creatine tends to be elevated to 15-20% above baseline (more than 20mM increase) in response to oral supplementation. People who get a sufficiently high influx of creatine are known as responders.[150][151][152][153] A phenomena known as “creatine nonresponse” occurs when people have less than a 10mM influx of creatine into muscle after prolonged supplementation.[154] Quasi-responders (10-20mM increase) also exist.[154] Nonresponse is thought to explain instances where people do not benefit from creatine supplementation in trials, since some trials that find no significant effect do find one when only investigating people with high creatine responsiveness.[155] There are clear differences between those who respond and those who do not, in regard to physical performance.[156] People who are creatine responsive tend to be younger, have higher muscle mass and type II muscle fiber content, but this has no correlation with dietary protein intake.[154][157]
Ancient Greek sculptures also depict lifting feats. The weights were generally stones, but later gave way to dumbbells. The dumbbell was joined by the barbell in the later half of the 19th century. Early barbells had hollow globes that could be filled with sand or lead shot, but by the end of the century these were replaced by the plate-loading barbell commonly used today.[3]

For the bench press, start with a weight that you can lift comfortably. If you are a beginner, try lifting the bar along with 5lbs or 10lbs on each side. With arms at shoulder-width apart, grab onto the bar and slowly lower the bar until it's at nipple level; push up until your arms are fully extended upwards. Do 8–10 repetitions (reps) like this for three sets (3 x 8), adding additional weight each set. Once you have a few months of practice, slowly increase weight and go down to 6–8 reps per set, aiming to reach muscle failure at the end of the third set.
^ Butenandt A, Hanisch G (1935). "Umwandlung des Dehydroandrosterons in Androstendiol und Testosterone; ein Weg zur Darstellung des Testosterons aus Cholestrin" [About Testosterone. Conversion of Dehydro-androsterons into androstendiol and testosterone; a way for the structure assignment of testosterone from cholesterol]. Hoppe-Seyler's Z Physiol Chem (in German). 237 (2): 89–97. doi:10.1515/bchm2.1935.237.1-3.89.
Achy knees are often written off as an inevitable side effect of getting older. And while it’s true knee pain has many age-related causes (namely, arthritis), chances are weak glutes are a big part of the problem, Kline says. If you’ve been diagnosed with arthritis, strengthening your glutes can at least help offset some of the pain you might experience, she says.
Kilduff, L. P., Georgiades, E., James, N., Minnion, R. H., Mitchell, M., Kingsmore, D., Hadjicharlambous, M., and Pitsiladis, Y. P. The effects of creatine supplementation on cardiovascular, metabolic, and thermoregulatory responses during exercise in the heat in endurance-trained humans. Int J Sport Nutr Exerc Metab 2004;14:443-460. View abstract.
Heath says to consume 1.25-2 grams of protein per pound of body weight for growth and he never exceeds a 1:1 meals to protein shake ratio, meaning if he has 3 shakes, he’ll have 3 meals. He suggests if you’re going to drink protein shakes, drink two and have four meals. Also, increase your protein consumption and decrease carbs to look lean. “Once I got to a certain size, I wanted to get leaner so I got to 50% protein, 30% carbs and 20% protein.”
In the hepatic 17-ketosteroid pathway of testosterone metabolism, testosterone is converted in the liver by 5α-reductase and 5β-reductase into 5α-DHT and the inactive 5β-DHT, respectively.[1][155] Then, 5α-DHT and 5β-DHT are converted by 3α-HSD into 3α-androstanediol and 3α-etiocholanediol, respectively.[1][155] Subsequently, 3α-androstanediol and 3α-etiocholanediol are converted by 17β-HSD into androsterone and etiocholanolone, which is followed by their conjugation and excretion.[1][155] 3β-Androstanediol and 3β-etiocholanediol can also be formed in this pathway when 5α-DHT and 5β-DHT are acted upon by 3β-HSD instead of 3α-HSD, respectively, and they can then be transformed into epiandrosterone and epietiocholanolone, respectively.[157][158] A small portion of approximately 3% of testosterone is reversibly converted in the liver into androstenedione by 17β-HSD.[156]
From here, push your hips back, and bend your knees to lower your body into a squat, not letting your knees cave in as you do so. Pause at the bottom for two seconds, then squeeze your glutes to return to standing. That’s one rep. Perform two sets of 10 reps, or as many as you can until you feel it in your legs. Aim to do this exercise three to four times per week.
Cross-legged gluteal stretch — Stand upright with one leg bent and your ankle placed over the opposite knee. Move your hips back as you squat and bring your arms forward to help you balance. Your standing leg should try to come parallel to the floor, and your crossed knee should be bent with your knee moving out to the side to help stretch the hips.
Fast twitch (or Type II fibers) fire very quickly, but also fatigue quickly, so they don’t last long.  It gets a bit more complicated, because there are actually two types of fast twitch fibers. Type IIA fibers have some endurance qualities (used for things such as longer sprints). While Type IIX fibers are our “super fast” fibers, used only when a super short burst is needed (like a 100 m sprint or a really heavy lift).
Elsewhere, it has been noted that in chronic progressive external ophthalmoplegia (CPEO, a progressive weakening of the muscles around the eye and a mitochondrial disorder), there was a failure of creatine supplementation to benefit symptoms when subjects were provided 20g daily for four weeks.[483] Creatine supplementation failed again at 150mg/kg for six weeks in people with either CPEO or another disorder associated with single gene deletions affecting the eyes (Kearns–Sayre syndrome, KSS) in improving muscular function.[484]
Lifters who follow high-volume or high-intensity resistance-training programs, as many bodybuilders do, may also benefit from carbohydrate intake immediately post-workout. Compared with a placebo, carbohydrates combined with protein immediately post-workout and one hour after a bout of resistance exercise have been shown to increase insulin levels and rates of glycogen resynthesis.[19]
A muscle imbalance—when one muscle is stronger than its opposing muscle—can limit your ability to exercise effectively, and could lead to injury down the line. “It’s important to recognize whether you’re really working the muscles you think you are and recognize if you’ve developed an imbalance that alters your movement pattern,” says Eric Ingram, physical therapist at Louisiana Physical Therapy Centers of Pineville. One common imbalance in women is stronger quads and weaker, tighter hamstrings, thanks to prolonged sitting, high heels, and improper training. If you suspect you have a muscle imbalance, make an appointment with a physical therapist, who will prescribe exercises to even you out.
There are many potential reasons, but I am going to keep it simple and give you just two. The first and most common reason people suffer from underactive glutes or “glute amnesia” is due to lifestyle. Even when people train hard every day, if they spend the majority of the remainder of the day sitting down, then they are simply not using their glutes. And remember the old saying - if you don’t use it, you lose it. Unfortunately, this is just what happens with your glutes.
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.
Studies of so-called "smart drugs" have also been taken out of context. Some "smart" nutrients, available over the counter, are marketed as a way to "increase mental focus and concentration during training." The problem is that the studies they're based upon involved either animals or people with brain pathology. In normal people the effects of smart drugs remain unproven, except anecdotally.
Bird, L. M., Tan, W. H., Bacino, C. A., Peters, S. U., Skinner, S. A., Anselm, I., Barbieri-Welge, R., Bauer-Carlin, A., Gentile, J. K., Glaze, D. G., Horowitz, L. T., Mohan, K. N., Nespeca, M. P., Sahoo, T., Sarco, D., Waisbren, S. E., and Beaudet, A. L. A therapeutic trial of pro-methylation dietary supplements in Angelman syndrome. Am J Med Genet.A 2011;155A(12):2956-2963. View abstract.
The hormone also plays a role in sex drive, sperm production, fat distribution, red cell production, and maintenance of muscle strength and mass, according to the Mayo Clinic. For these reasons, testosterone is associated with overall health and well-being in men. One 2008 study published in the journal Frontiers of Hormone Research even linked testosterone to the prevention of osteoporosis in men.
It was later noted that creatine was able to nonsignificantly augment various proinflammatory cytokines (CCL2, iNOS, ICAM-1, TGF-β, TIMP-1) and the presence of eosinophils in lung tissue, as well as to per se cause lung infiltration of these immune cells without requiring the presence of the allergen.[442] Neutrophils and macrophages were unaffected,[442] reflecting the past study of no influence on macrophages,[440] but the only instance where creatine appeared to either significantly add to ovalbumin or to per se induce statistically significant increases were in IL-5 secretion and goblet cell infiltration, although VCAM-1 expression was close. While creatine per se increased nF-κB activity, it suppressed the ovalbumin-induced increase.[442]
Replacement therapy may produce desired results, such as greater muscle mass and a stronger sex drive. However, the treatment does carry some side effects. Oily skin and fluid retention are common. The testicles may also shrink, and sperm production could decrease significantly. Some studies have found no greater risk of prostate cancer with testosterone replacement therapy, but it continues to be a topic of ongoing research.
In general, muscle content of creatine tends to be elevated to 15-20% above baseline (more than 20mM increase) in response to oral supplementation. People who get a sufficiently high influx of creatine are known as responders.[150][151][152][153] A phenomena known as “creatine nonresponse” occurs when people have less than a 10mM influx of creatine into muscle after prolonged supplementation.[154] Quasi-responders (10-20mM increase) also exist.[154] Nonresponse is thought to explain instances where people do not benefit from creatine supplementation in trials, since some trials that find no significant effect do find one when only investigating people with high creatine responsiveness.[155] There are clear differences between those who respond and those who do not, in regard to physical performance.[156] People who are creatine responsive tend to be younger, have higher muscle mass and type II muscle fiber content, but this has no correlation with dietary protein intake.[154][157]
These effects are secondary to creatine being a source of phosphate groups and acting as an energy reserve. The longer a cell has energy, the longer it can preserve the integrity of the cell membrane by preserving integrity of the Na+/K+-ATPase and Ca2+-ATPase enzymes.[241][235][236] Preserving ATP allows creatine to act via a nongenomic response (not requiring the nuclear DNA to transcribe anything), and appears to work secondary to MAPK and PI3K pathways.[226]
In October 1994, the Dietary Supplement Health and Education Act (DSHEA) was signed into law in the USA. Under DSHEA, responsibility for determining the safety of the dietary supplements changed from government to the manufacturer and supplements no longer required approval from the U.S. Food and Drug Administration (FDA) before distributing product. Since that time manufacturers did not have to provide FDA with the evidence to substantiate safety or effectiveness unless a new dietary ingredient was added. It is widely believed that the 1994 DSHEA further consolidated the position of the supplement industry and lead to additional product sales.[6]
Aim to eat roughly 250 to 500 extra calories per day. To make sure that any weight gained is from muscle, Fitzgerald recommends that the bulk of those calories come from protein. In a 2014 Pennington Biomedical Research Center study, people who ate a high-calorie diet rich in protein stored about 45 percent of those calories as muscle, while those following a low-protein diet with the same number of calories stored 95 percent of those calories as fat.
Another supplement that’s ideal to take pre-workout is protein. Depending on your goals and your workout time, taking protein before your workout can help you keep your energy levels elevated while working out. Make sure you give yourself at least an hour between the time you take your protein and your workout time so that your body has time to digest.
Some of the most common minor side effects include stomach discomfort, nausea, and increased bowel movements. Other potential side effects may include headaches, bloating, and increased thirst. There is always the chance that a supplement could cause an allergic reaction. This can result in rashes, swelling, or difficulty breathing, depending on the severity of the reaction. This is another reason why starting out with lower doses of new products is advisable.
×