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].

If you’re the kind of person who shops for popular dietary supplements like protein or collagen powder, you’ve probably seen another popular bottle on the shelves: creatine. This supplement, which can be taken as a powder or liquid (and usually in some kind of healthy shake), is a staple in the bodybuilding community thanks to its ability to help you pack on muscle and work out longer and harder. (1) While creatine is generally considered safe — and is one of the most researched supplements out there (according to a review published in July 2012 in the Journal of the International Society of Sports Nutrition) — it is still a supplement, which means it’s not regulated by the Food and Drug Administration (FDA) and product claims don’t necessarily need to be substantiated (though the FDA can pull products that are found to be unsafe). (2,3)


Retinol (Vitamin A) B vitamins: Thiamine (B1) Riboflavin (B2) Niacin (B3) Pantothenic acid (B5) Pyridoxine (B6) Biotin (B7) Folic acid (B9) Cyanocobalamin (B12) Ascorbic acid (Vitamin C) Ergocalciferol and Cholecalciferol (Vitamin D) Tocopherol (Vitamin E) Naphthoquinone (Vitamin K) Calcium Choline Chromium Cobalt Copper Fluorine Iodine Iron Magnesium Manganese Molybdenum Phosphorus Potassium Selenium Sodium Sulfur Zinc
Our bodies store creatine in our muscles so that we have quick access to it for fast, high-intensity movements, like sprinting or powerlifting, explains Autumn Bates, a certified clinical nutritionist and sports nutritionist in private practice in Manhattan Beach, California. “It's a nonessential amino acid, meaning your body creates it and you don't need to primarily get it from food.”
Who makes it: Creapure HMB is made by Transparent Labs, one of the best companies in the sports nutrition industry. Transparent labs is all about, well, transparency! They always clearly list everything that goes into their products. They use pure, simple, and clinically proven ingredients to create products that get real results. Instead of relying on marketing gimmicks to sell their products, Transparent Labs relies on proven science and word-of-mouth. Transparent Labs has grown their business by providing the one ingredient seldom found in sports nutrition products: honesty.
At the end of the day, you have to focus on how you feel. “Listen to your body,” says Davis. “It tells you when it needs a day off.” As a rule of thumb, take a rest day if your perceived pain is above a seven on a scale of 10, Davis advises. Or, focus on a different body part (say, if your legs are sore, focus on upper-body moves). Can't stop, won't stop—at least, till your next rest day.
You’d have to look hard to find a fitness expert who doesn’t recommend taking supplemental protein powder for building muscle. It’s one of the best supplements for building muscle on the market! In addition to serving as a muscle building supplement, protein powder can be the perfect complement to a successful weight loss plan. Studies show that the supplement can prevent loss of muscle mass, helping you lose fat exclusively instead.
Bottom Line: Con-Cret is one of the best creatine HCI products available. Its unique use of creatine HCI allow it to offer all the great benefits of creatine, without the bloating and water retention that creatine monohydrate sometimes causes – making Con-Cret a good creatine to take if you’re concerned about the potential for bloating with other products.

"It'’s especially important to eat a carb- and protein-rich meal immediately after a workout," Aceto says. "Right after training, it turns out that your body is really lousy at taking carbohydrates and sending them down fat-storing pathways,"” he says. "So post-training, carbs will be sent down growth-promoting pathways instead."” And when these carbs are combined with a protein source, you'’ve got a strong muscle-feeding combination because carbohydrates help deliver the amino acids into muscles by boosting insulin levels. This anabolic hormone drives nutrients into the muscle cells and kick-starts the muscle-growth process.


In a pilot study on youth with cystic fibrosis, supplementation of creatine at 12g for a week and 6g for eleven weeks afterward was associated with a time-dependent increase in maximal isometric strength reaching 14.3%, which was maintained after 12-24 weeks of supplement cessation (18.2% higher than baseline).[485] This study noted that more patients reported an increase in wellbeing (9 subjects, 50%) rather than a decrease (3, 17%) or nothing (6, 33%) and that there was no influence on chest or lung symptoms.[485]
The main storage area of creatine in the human body is the skeletal (contractile) muscle, which holds true for other animals. Therefore, consumption of skeletal muscle (meat products) is the main human dietary source of creatine. Since vegetarians and vegans lack the main source of dietary creatine intake, which has been estimated to supply half of the daily requirements of creatine in normal people, both vegetarians and vegans have been reported to have lower levels of creatine.[58][59] This also applies to other meat-exclusive nutrients, such as L-Carnitine.[58]
You have to fuel your body with high-quality, real, wholesome food. Eating pizza, burgers, ice cream, and fast food just because it’s high in calories is a really bad plan. You’ll feel terrible, and while the extra calories will help muscle gains to an extent, most of them will turn to fat. It’s not worth it. Your recovery will be slower and you will be riddled with inflammation.
“Compared to training for strength, intensity is going to drop during the hypertrophy phase of a program, with intensity sitting between 50 and 75 percent of the person’s 1RM, the maximum weight he or she can lift for one rep,” says Ava Fitzgerald, C.S.C.S., C.P.T., a sports performance coach with the Professional Athletic Performance Center in New York.

In patients with DM1 given a short loading phase (10.6g for ten days) followed by a 5.3g maintenance for the remainder of an 8-week trial noted that supplementation resulted in a minor improvement in strength (statistical significance only occurred since placebo deteriorated) and no significant difference was noted in self-reported perceived benefits.[565] Maintaining a 5g dosage for four months also failed to significantly improve physical performance (handgrip strength and functional tests) in people with DM1, possible related to a failure to increase muscular phosphocreatine concentrations.[566]
Need the motivation to push past your comfort zone and squeeze out one more push-up or bicep curl? Sure, it helps to remember that you’ll get stronger, rock more toned muscles and rev your metabolism, thanks to all that added muscle mass. But if that wasn’t enough, now comes news that all that pump-itude (yes, that’s an SNL reference) has psychological benefits, too.
You may be wondering what conditions and medications contraindicate the use of creatine supplements. Creatine is contraindicated in people with kidney insufficiency or kidney disease. If you take diabetes medication, diuretics or acetaminophen, do not take a creatine supplement. Use caution if you regularly consume caffeine while taking a creatine supplement. Overall, if you are healthy and have gotten clearance from your doctor, consider this non-GMO creatine supplement.
Creatine is a molecule produced in the body. It stores high-energy phosphate groups in the form of phosphocreatine. Phosphocreatine releases energy to aid cellular function during stress. This effect causes strength increases after creatine supplementation, and can also benefit the brain, bones, muscles, and liver. Most of the benefits of creatine are a result of this mechanism.
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People sometimes walk up and touch him, as if unsure if he is a man or a machine. What they do not realize is that beneath the stony exterior and self-assuredness is a squishy sense of anxiety and vulnerability. Heath gets nervous every time he strips to his posing trunks. He is rarely satisfied with what he sees in the mirror. He is persistently worried about imperfections others might find, too.
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].
The concentration in healthy controls (57+/-8 years) without supplementation of creatine appears to be around 1.24+/-0.26µM per gram of hemoglobin[292] and appears to decrease in concentration during the aging process of the erythrocyte.[294][295][296] Otherwise healthy subjects who take a loading phase of creatine (5g four times daily for five days) can experience a 129.6% increase in erythrocytic creatine concentrations from an average value of 418µM (per liter) up to 961µM with a large range (increases in the range of 144.4-1004.8µM),[297] and this effect appears to correlate somewhat with muscular creatine stores.[297]
Other supplements could easily have been included here, but these are considered the most useful and effective for the majority of bodybuilders and athletes. Although food should always come first, supplements offer an effective alternative for getting nutrients that either aren't available in sufficient quantity in food or are in foods that you may not be eating.
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.
Beach muscles and Olympic lifts draw more attention. But the many little stabilizer muscles around your shoulders, hips, and midsection — collectively the core — provide a strong foundation. Challenging the stability and mobility of these key muscles with medicine balls, physioballs, mini-bands, and rotational movements (lifting, chopping) pays huge dividends.
Different exercises will require different weights, but there are some markers that can help guide you towards the right resistance, whether you're using dumbbells, kettlebells, or a barbell. Go for a weight that feel heavy enough to challenge you, but not so heavy that you sacrifice your form. For example, if you're doing 15 reps, you should feel pretty fatigued by the time you hit rep 15. If you can breeze through all your reps, though, that's a sign you should up the weight.
Another study found that one week of creatine supplementation at 25 g/day enhanced muscular performance during repeated sets of bench press and jump squat exercise. Creatine supplementation appeared to allow the subjects to complete their workouts at a higher intensity. The researchers concluded that, over time, working at higher intensities may provide a more intense training stimulus and improved muscular adaptations [10].
Muscle growth is more difficult to achieve in older adults than younger adults because of biological aging, which leads to many metabolic changes detrimental to muscle growth; for instance, by diminishing growth hormone and testosterone levels. Some recent clinical studies have shown that low-dose HGH treatment for adults with HGH deficiency changes the body composition by increasing muscle mass, decreasing fat mass, increasing bone density and muscle strength, improves cardiovascular parameters, and affects the quality of life without significant side effects.[45][46][unreliable medical source?][47]
Those 5-pound dumbbells were a great place to start as a beginner, but if you've been lifting weights for a while, it's time to bump up the weight. “You can use both exercise machines and free weights,” explains Michele Olson, PhD, exercise physiologist, professor of exercise science at Auburn University Montgomery, “but, if you are not lifting heavy enough weight, it doesn’t matter if you are primarily using free weights or machines.” In order to build muscle, you must break down muscle tissue using a weight that is challenging enough to cause micro-tears, which when repaired, form denser, stronger fibers.
Another favorite bodybuilding supplement, creatine is an amino acid found in the body. The highest levels of this molecule are in your muscles and brain. It is made by your liver, pancreas and kidneys, but is also found in foods including meat, eggs and fish. Research has shown that it may help athletes including weightlifters who need short bursts of energy (5). In this study, creatine monohydrate proved to be an effective muscle builder. It works to improve body composition, muscle mass, strength and power.  Note that it was also more effective than other forms of creatine. How does it do this?
At the end of the day, yes, strength training does impact your metabolism, but any boost you get will be minimal and completely secondary to all of the other health benefits of strength training. Any change in metabolism or increase in calorie burn will vary widely from person to person, and depends on so many factors: your genetics, eating habits, health conditions, what workout you do that day, how much sleep you’re getting, and even how stressed you are on any given day. But incorporating a couple of strength training sessions into your fitness routine is worth doing no matter what—you’ll feel yourself get stronger, and put yourself in a position to say healthier throughout life. Those are the best, most promising benefits to work for.

Creatine citrate is creatine bound to citric acid, or citrate. Creatine citrate does not differ greatly from monohydrate in regard to absorption or kinetics.[83] Note that creatine citrate is more water-soluble than monohydrate,[84] but creatine absorption is generally not limited by solubility. The increased water solubility may play a factor in palatability.

It can be hard to know where to start when beginning strength training. There are countless exercises you can do, some of which work some muscles, but not others. There are safety concerns to beware of, a wide variety of sometimes confusing equipment to help you in your efforts, and so on. With some familiarity of the basics of getting started with strength training, actually doing so can become far less daunting, and you can begin to craft a routine that is targeted toward helping you achieve your personal goals.

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.
^ "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.
Walking, running, and swimming are examples of activity. Aerobic activity strengthens your heart and lungs. Stretching improves your flexibility. Strength training uses resistance, like free weights, weight machines, resistance bands, or a person's own weight, to build muscles and strength. Teens may want to strength train to improve sports performance, treat or prevent injuries, or improve appearance.

Eat 1.5–3 grams of carbs per pound of your body weight. As with fat, this amount can vary greatly, depending on your personal needs and preferences, so consider these numbers only a starting point. If you’re very skinny and feel that you handle carbs well (i.e. you can eat a lot of them without getting fat), go ahead and eat according to the higher end of the spectrum. The same applies if you’re desperate to gain weight—you should increase your carb intake. If you’re prone to weight gain or feel lethargic on higher carbs, you should eat fewer of them. Again, see our keto guide for more details and options.
Lung disease (Chronic obstructive pulmonary disease). Early research on the effects of creatine in people with chronic obstructive pulmonary disease (COPD) is inconsistent. Some research suggests that taking creating daily does not improve lung function. However, other research suggests that taking creatine may improve lung function or exercise capacity.
The neuroprotective effects of creatine appear to exist in regard to dopamine biosynthesis, and the suppression of dopamine synthesis seen with some neurological toxins appears to be partially attenuated with dietary intake of creatine. The protective effect is weak to moderate in animal research, but appears to be additive with anti-inflammatories.

Many athletes follow a "loading" protocol of around 25 grams a day for five days, but this isn't essential. But as Ciaran Fairman notes in the article "Do I Need to Load With Creatine," you can also get the same benefits with around 5 grams a day, potentially with none of the mild side effects of the loading protocol, which include stomach pain and water weight gain. The catch is that you have to take it consistently. Don't skip it!
Lie on your back on the floor and bend one knee so that your foot is flat on the floor. Keeping your opposite leg straight, push your foot into the floor, raising your hips until both thighs are in line with each other. Reverse the motion to return to the starting position. That’s one rep. Complete all your reps on one leg, and then switch legs and repeat.
A retrospective study [81], that examined the effects of long lasting (0.8 to 4 years) CM supplementation on health markers and prescribed training benefits, suggested that there is no negative health effects (including muscle cramp or injuries) caused by long term CM consumption. In addition, despite many anecdotal claims, it appears that creatine supplementation would have positive influences on muscle cramps and dehydration [82]. Creatine was found to increase total body water possibly by decreasing the risk of dehydration, reducing sweat rate, lowering core body temperature and exercising heart rate. Furthermore, creatine supplementation does not increase symptoms nor negatively affect hydration or thermoregulation status of athletes exercising in the heat [83,84]. Additionally, CM ingestion has been shown to reduce the rate of perceived exertion when training in the heat [85].
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]
What are the benefits of konjac? Konjac is a plant with a starchy root, or corm. This corm is used in dietary supplements and in the production of jellies and flour. Find out more about the potential health benefits of konjac, including managing diabetes, reducing cholesterol, and treating constipation. Get some tips, too, on how to use it safely. Read now
Bottom Line: Con-Cret is one of the best creatine HCI products available. Its unique use of creatine HCI allow it to offer all the great benefits of creatine, without the bloating and water retention that creatine monohydrate sometimes causes – making Con-Cret a good creatine to take if you’re concerned about the potential for bloating with other products.
Anti-depressive effects have been noted in woman with major depressive disorder when 5g of creatine monohydrate was supplemented daily for 8 weeks in combination with an SSRI. Benefits were seen at week two and were maintained until the end of the 8-week trial.[253] The improvement in depressive symptoms was associated with significantly increased prefrontal cortex levels of N-acetylaspartate, a marker of neuronal integrity,[254] and rich club connections, which refers to the ability of nerons to make connections to one another.[255]

Several review studies assessing the safety of creatine supplementation tend to make note of increases in formaldehyde and possible carcinogenic results.[451][452] Specifically, creatine is metabolized into an intermediate called methylamine, which can be converted to formaldehyde by the SSAO enzyme.[453] An increase in urinary formaldehyde has been noted in youth given 21g of creatine for one week, during which both methylamine (820% increase) and formaldehyde (350%) were increased, relative to control.[454] However, a more prolonged study using 300mg/kg (loading dose of around 20g) in adults for ten weeks failed to replicate these effects.[455]
^ Kreider RB, Kalman DS, Antonio J, Ziegenfuss TN, Wildman R, Collins R, Candow DG, Kleiner SM, Almada AL, Lopez HL (2017-06-13). "International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine". Journal of the International Society of Sports Nutrition. 14: 18. doi:10.1186/s12970-017-0173-z. PMC 5469049. PMID 28615996.

A: Start with the calculations above but don’t be afraid to adjust up or down. Your metabolism and physiology will adapt to more food by trying to maintain homeostasis and regulate your bodyweight. Some may have to increase more than others but the number on the scale doesn’t lie. If it’s not going up, then you probably need to increase your calories.


Beginners are advised to build up slowly to a weight training program. Untrained individuals may have some muscles that are comparatively stronger than others; nevertheless, an injury can result if (in a particular exercise) the primary muscle is stronger than its stabilizing muscles. Building up slowly allows muscles time to develop appropriate strengths relative to each other. This can also help to minimize delayed onset muscle soreness. A sudden start to an intense program can cause significant muscular soreness. Unexercised muscles contain cross-linkages that are torn during intense exercise. A regimen of flexibility exercises should be implemented before weight training begins, to help avoid soft tissue pain and injuries.
Without a doubt, you can add muscle simply by eating right and lifting weights. But to truly maximize your growth potential, supplements are a requirement. Hence, we've compiled a rundown of the 11 best mass-gain supplements on which to spend your hard-earned cash. They're listed in order of priority, from the absolute most critical, can't-do-without supplements to the less crucial yet still highly effective ingredients for packing on size. The point is to help those on a tight budget decide which supplements to buy. If money is no object, then by all means knock yourself out and use them all as directed. Because after all, as far as we're concerned, you can never have too much muscle.

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:
COX-2, a pro-inflammatory enzyme, is sometimes a therapeutic target for both muscle soreness and some degenerative diseases that are exacerbated by inflammation. COX-2 inhibitors (in this study, rofecoxib) and creatine monohydrate both appear to protect dopaminergic neurons from being destroyed by toxins, and can protect in an additive manner, suggesting possible usage of both to reduce the risk of Parkinson’s disease.[230]
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] 

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.
Competitive and professional bodybuilders, however, can often build up to two to three pounds of muscle per month during dedicated bulking periods. "But they are living and breathing muscle growth. They aren't just in and out of the gym like most people," Simpson says, noting that under extreme conditions, hyperplasia, or the growth in the number of muscle cells in a given muscle tissue, may actually occur, further adding to muscle growth results.

Syrotuik and Bell [57] investigated the physical characteristics of responder and non-responder subjects to creatine supplementation in recreationally resistance trained men with no history of CM usage. The supplement group was asked to ingest a loading dosage of 0.3 g/kg/d for 5 days. The physiological characteristics of responders were classified using Greenhaff et al [58] criterion of >20 mmol/kg dry weight increase in total intramuscular creatine and phosphocreatine and non responders as <10 mmol/kg dry weight increase, a third group labeled quasi responders were also used to classify participants who fell in between the previously mentioned groups (10-20 mmol/kg dry weight). Overall, the supplemented group showed a mean increase in total resting muscle creatine and phosphocreatine of 14.5% (from 111.12 ± 8.87 mmol/kg dry weight to 127.30 ± 9.69 mmol/kg dry weight) whilst the placebo group remained relatively unaffected (from 115.70 ± 14.99 mmol/kg dry weight to 111.74 ± 12.95 mmol/kg dry weight). However when looking at individual cases from the creatine group the results showed a variance in response. From the 11 males in the supplemented group, 3 participants were responders (mean increase of 29.5 mmol/kg dry weight or 27%), 5 quasi responders (mean increase of 14.9 mmol/kg dry weight or 13.6%) and 3 non-responders (mean increase of 5.1 mmol/kg dry weight or 4.8%). Using muscle biopsies of the vastus lateralis, a descending trend for groups and mean percentage fiber type was observed. Responders showed the greatest percentage of type II fibers followed by quasi responders and non-responders. The responder and quasi responder groups had an initial larger cross sectional area for type I, type IIa and type IIx fibers. The responder group also had the greatest mean increase in the cross sectional area of all the muscle fiber types measured (type I, type IIa and type IIx increased 320, 971 and 840 μm2 respectively) and non-responders the least (type I, type IIa and type IIx increased 60, 46 and 78 μm2 respectively). There was evidence of a descending trend for responders to have the highest percentage of type II fibers; furthermore, responders and quasi responders possessed the largest initial cross sectional area of type I, IIa and IIx fibers. Responders were seen to have the lowest initial levels of creatine and phosphocreatine. This has also been observed in a previous study [17] which found that subjects whose creatine levels were around 150 mmol/Kg dry mass did not have any increments in their creatine saturation due to creatine supplementation, neither did they experience any increases of creatine uptake, phosphocreatine resynthesis and performance. This would indicate a limit maximum size of the creatine pool.
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].
Synthesis primarily takes place in the kidney and liver, with creatine then being transported to the muscles via the blood. The majority of the human body's total creatine and phosphocreatine stores is located in skeletal muscle, while the remainder is distributed in the blood, brain, and other tissues.[17][18][20] Typically, creatine 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.[17][18] Some small studies suggest that total muscle creatine is significantly lower in vegetarians than non-vegetarians, as expected since foods of animal origin are the primary source of creatine. However, subjects happened to show the same levels after using supplements.[21]
In humans, studies that investigate links between serotonin and creatine supplementation find that 21 trained males, given creatine via 22.8g creatine monohydrate (20g creatine equivalent) with 35g glucose, relative to a placebo of 160g glucose, was found to reduce the perception of fatigue in hot endurance training, possibly secondary to serotonergic modulation, specifically attentuating the increase of serotonin seen with exercise (normally seen to hinder exercise capacity in the heat[233]) while possibly increasing dopaminergic activity (conversely seen to benefit activity in the heat[234]).[155]
Creatine non-response is when muscular loading of creatine is under a certain threshold (10mmol/L), while “response” to creatine means having more muscular creatine loading (20mol/L or more). There also exists a “grey area” inbetween, where some benefits are achieved but not as many as pure responders will experience. Response appears to be positively correlated with muscle mass and type II muscle fibers.
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]
When assessing the antioxidant effects of creatine, it does not appear to sequester superoxide and may not be a direct antioxidant.[241] Additionally, creatine failed to protect neurons from H2O2 incubation to induce cell death via pro-oxidative means.[241] These results are in contrast to previously recorded results suggesting creatine acts as a direct anti-oxidant.[242]
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