Whey, the liquid remaining after milk has been curdled and strained, is rapidly digested and absorbed and has a remarkable ability to stimulate muscle protein synthesis (Hayes & Cribb, 2008). Whey is available in three varieties — whey protein powder, whey protein concentrate, whey protein isolate — and all provide high levels of the essential and branched chain amino acids, vitamins and minerals.
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.

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]


In today's extra-large society, we tend to focus on the admirable guys who train hard and switch up their diet to transform their bodies by losing weight. We highlight their quests to lead healthier lives every chance we get — but there's another side of the wellness scale that can be just as difficult, depending on your body's makeup: Gaining mass and muscle.

Of the three, protein will of course play the most important role in the muscle building process (like calories, it’s one our required “supplies”), although fat and carbs will still be important for other reasons which range from optimizing hormone production (e.g. testosterone, the muscle building hormone) to enhancing training performance and recovery.
Creatine supplementation (11.4g) with glycerol (1g/kg; per se effective[394][395]) and glucose (75g) in endurance runners in the heat appears to attenuate the increase in internal temperature associated with an increase in total body water of 0.71+/-0.42L, while performance (VO2 max and running economy) were unaffected over 30 minutes.[3] Creatine is effective without glycerol (20g daily with 140g of glucose polymer over a week),[346] again without an improvement in physical performance.
Listen, I know in the beginning of this post I was sympathetic to your problem, but I am also here to say, Suck It Up. I can tell you that to gain weight, you need to focus on making your meals a habit rather than an afterthought. Your body is pre-programmed with your genetic disposition. And in your case, you have a very fast metabolism that digests and burns calories quickly. Focus on having 5-6 calorie-dense meals a day spaced 2-3 hours apart so that your body is constantly being provided with something to metabolize and build muscle.
2-4 Minutes Rest: Ideal for “tension exercises,” which includes most primary compound exercises. I personally take 3 minutes for the big stuff, sometimes going into the 3-4 minute range depending on exactly what I’m doing and what I feel like I need at the time. Since making strength gains is the main focus of these exercises, longer rest periods like this will be optimal for making it happen.
I know this goes against the recommendations you often see in stereotypical bodybuilding routines (i.e. the ones that involve having a single “chest day” or “arm day” or “shoulder day” once a week), but that’s just one of the many reasons why those types of routines suck for us natural, genetically-average people, and work best for steroid users with great genetics.
Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) is a synthetic analogue of creatine in a cyclic form. It serves as a substrate for the creatine kinase enzyme system, acting as a creatine mimetic. Cyclocreatine may compete with creatine in the CK enzyme system to transfer phosphate groups to ADP, as coincubation of both can reduce cyclocreatine’s anti-motility effects on some cancer cells.[96]
Antioxidants in the diet protect against natural and synthetic chemical fragments called free radicals that are a part of daily living. Lifestyle challenges may increase your requirements for antioxidants. Vitamin C and E are the main antioxidants in the normal diet although many other plant nutrients contribute to this effect. Pollution, stress, smoking, strenuous exercise, and illness may increase your requirements for antioxidant protection.
This copyrighted, evidence-based medicine resource is provided by Natural Medicines Comprehensive Database Consumer Version. Natural Medicines Comprehensive Database disclaims any responsibility related to consequences of using any product. This monograph should not replace advice from a healthcare professional and should not be used for the diagnosis or treatment of any medical condition.
A 2011 survey of 33 supplements commercially available in Italy found that over 50% of them exceeded the European Food Safety Authority recommendations in at least one contaminant. The most prevalent of these contaminants was creatinine, a breakdown product of creatine also produced by the body.[47] Creatinine was present in higher concentrations than the European Food Safety Authority recommendations in 44% of the samples. About 15% of the samples had detectable levels of dihydro-1,3,5-triazine or a high dicyandiamide concentration. Heavy metals contamination was not found to be a concern, with only minor levels of mercury being detectable. Two studies reviewed in 2007 found no impurities.[41]
Of course, cardio is an important part of fitness too, but the benefits of strength training are major. Strength training helps build muscle, and lean muscle is better at burning calories when the body is at rest, which is important whether you're trying to lose weight or maintain it. It also helps strengthens joints and bones, avoid injury, improve your muscular endurance, and will help you give it your all during your other workouts, whether that means setting a new PR if you're a runner or pushing (and pulling) a little harder with your legs during your favorite indoor cycling class.
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]
In contrast to the above null effects, ingestion of creatine both before and after a workout (alongside protein and carbohydrate) over 10 weeks seems to promote muscle growth more than the same supplement taken in the morning, farther away from the time of the workout.[386] The benefits of creatine around the workout, relative to other times, have been hypothesized[387] to be related to an upregulation of creatine transport secondary to muscle contraction, a known phenomena.[153]

Lyoo, I. K., Yoon, S., Kim, T. S., Hwang, J., Kim, J. E., Won, W., Bae, S., & Renshaw, P. F. (2012, September). A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder. American Journal of Psychiatry. 169(9):937-45. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22864465
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.

Boosting your workouts with an intra-workout catalyst, Scivation's XTEND holds a revolutionary formula that is both free of sugar and carbohydrates in a powerful BCAA drink mix. Using the 2:1:1 BCAA ratio with 7 grams in each serving, the advanced design of this supplement aids in the building of muscle, incinerating of fat, and shortening of recovery, while supporting hydration with a proprietary blend of electrolytes. XTEND encourages the optimal synthesizing of protein and fuels the body with energy for a power-filled workout. Keep Reading »
AAOS does not endorse any treatments, procedures, products, or physicians referenced herein. This information is provided as an educational service and is not intended to serve as medical advice. Anyone seeking specific orthopaedic advice or assistance should consult his or her orthopaedic surgeon, or locate one in your area through the AAOS Find an Orthopaedist program on this website.
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]
Creatine is stored in the body in the form of creatine and as creatine phosphate, otherwise known as phosphocreatine, which is the creatine molecule bound to a phosphate group.[39] Creatine phosphate is thought to maintain the ATP/ADP ratio by acting as a high-energy phosphate reservoir.[40] The more ATP a muscle has relative to ADP, the higher its contractility is, and thus its potential strength output in vivo.[41][42] This pro-energetic mechanism also affects nearly all body systems, not just skeletal muscle. [39] During periods of rest and anabolism, creatine can gain a phosphate group through the creatine-kinase enzyme pathway, up to a cellular concentration of 30uM[24] to be later used for quick ATP resupply, when needed.[43][44] 

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.
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 8-12 reps for muscular strength and 10-15 reps for muscular endurance. They also recommend at least 1 set of each exercise to fatigue although you'll find that most people perform about 2-3 sets of each exercise. In general:
While many of the claims are based on scientifically based physiological or biochemical processes, their use in bodybuilding parlance is often heavily colored by bodybuilding lore and industry marketing and as such may deviate considerably from traditional scientific usages of the terms. In addition, ingredients listed have been found at times to be different from the contents. In 2015, Consumer Reports reported unsafe levels of arsenic, cadmium, lead and mercury in several of the protein powders that were tested.[7]

Rice Protein: An alternative protein powder for muscle gain, rice protein is ideal for people who are lactose intolerant or have a milk allergy. As far as muscle gain and body composition when taken post-workout, this study showed that there was zero difference in outcomes when comparing taking whey protein and rice protein. So, if you prefer using rice protein, you can take it with confidence knowing that you’ll be able to achieve the same results you’d achieve if you were taking whey protein.
Include cardio training. Good cardiovascular health improves blood flow, a requirement for muscle growth. Doing cardio also improves your cardiovascular fitness, which allows you to use your muscle gains for various sports and activities. The standard recommendation is 150 minutes of moderate cardio each week, or 75 minutes of vigorous cardio, or an equivalent combination of the two. A good place to start would be doing 30-60 minutes of cardiovascular activity every other day or 3 times a week. Examples of cardio include running, biking, swimming, and any sport that involves constant movement.
Some people do have allergies to soy, or they have an intolerance to soy. If you notice certain symptoms (like a headache) after soy consumption, you may have an intolerance. Discovering your food intolerances/allergies would also be handled by a Dietitian. For the general population who are not allergic/intolerant to soy, however, soy-based products can be a part of a healthy diet. New research has shown that soy is not harmful as people fear. If soy gives you issues, you could always opt for whey protein, pea protein or other forms of vegetable protein. Have you seen our article on protein powders? Click here.
In addition to the BBB, SLC6A8 is also expressed on neurons and oligodendrocytes,[192] but is relatively absent from astrocytes, including the astrocytic feet[193][194] which line 98% of the BBB.[195] Creatine can still be transported into astrocytes (as well as cerebellar granule cells) via SLC6A8, as incubation with an SLC6A8 inhibitor prevents accumulation in vitro. It seems to be less active in a whole brain model, relative to other brain cells.[196]
One case study on a subject with a methylentetrahydrofolate reductase (MTHFR) 677TT homozygote, a relatively common genetic mutation known as “mild MTHFR deficiency,” which causes mild homocysteinemia,[310] has seen benefits due to creatine supplementation where homocysteine was approximately halved (49% reduction) while CT heterozygotes and CC homozygotes (n=9) were unaffected.[311] Additionally, one rat study suggested a possible role for creatine in reducing homocysteine levels in a model of high uric acid levels (model for end stage renal disease[312]) but this was not replicated when investigated in humans.[313]
The biggest mistake among young would-be bodybuilders is overdoing it, followed by not learning the proper techniques. Take those breaks and follow the correct form, or you'll give your body stress and injuries instead of muscle. Also make sure you're getting a large but balanced diet. Teens going through growth spurts need lots of food, especially when they're working out.
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.
Creatine was first identified in 1832 when Michel Eugène Chevreul isolated it from the basified water-extract of skeletal muscle. He later named the crystallized precipitate after the Greek word for meat, κρέας (kreas). In 1928, creatine was shown to exist in equilibrium with creatinine.[3] Studies in the 1920s showed that consumption of large amounts of creatine did not result in its excretion. This result pointed to the ability of the body to store creatine, which in turn suggested its use as a dietary supplement.[4]
That said, many people experience stomach cramps when they consume creatine monohydrate and it’s possible that taking a creatine with a different pH — usually creatine hydrochloride — can have a different effect on stomach acid and make for a creatine that digests more easily. As far as we know, the easier digestion doesn’t necessarily mean it’s more effective or that you need less of it to achieve the desired result.
Still, it's important to realize that for everyone, at a certain point, building muscle becomes more difficult. "We all have an endpoint to our genetic potential," Matheny says. "Someone who is starting strength training for the first time can build muscle with a lower percentage of their 1RM [the maximum amount of weight they can lift one time] than a more tenured athlete. The longer you train and the closer you to get to your natural potential, the more specific you need to get with your training and nutrition to keep making progress. And that week-by-week progress will likely be much smaller than it once was."
Many trainees like to cycle between the two methods in order to prevent the body from adapting (maintaining a progressive overload), possibly emphasizing whichever method more suits their goals; typically, a bodybuilder will aim at sarcoplasmic hypertrophy most of the time but may change to a myofibrillar hypertrophy kind of training temporarily in order to move past a plateau. However, no real evidence has been provided to show that trainees ever reach this plateau, and rather was more of a hype created from "muscular confusion".[clarification needed][citation needed]
Antioxidants in the diet protect against natural and synthetic chemical fragments called free radicals that are a part of daily living. Lifestyle challenges may increase your requirements for antioxidants. Vitamin C and E are the main antioxidants in the normal diet although many other plant nutrients contribute to this effect. Pollution, stress, smoking, strenuous exercise, and illness may increase your requirements for antioxidant protection.
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 8-12 reps for muscular strength and 10-15 reps for muscular endurance. They also recommend at least 1 set of each exercise to fatigue although you'll find that most people perform about 2-3 sets of each exercise. In general:
A study showed that 100mg/kg creatine monohydrate daily over four months supplemented by boys with DMD is able to enhance handgrip strength in the dominant hand only (less than 10% increase) and increase whole-body lean mass. While the trend toward whole body strength reduction seen in placebo was ablated and there was no interaction with corticosteroids,[560] this study failed to find an influence on activities of daily living or lung function.[560] Elsewhere in children not on corticosteroids with DMD, supplementation of 5g creatine for eight weeks was confirmed to increase muscular phosphocreatine content[554] and according to a manual muscle test (MMT) there was a significant improvement in muscular function relative to placebo, with more parents reporting benefit with creatine (53.8%) relative to placebo (14%).[554]
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]
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] 

It’s true—your genes can play a role when it comes to building muscle. In general, there are two types of muscle fibers: Type I, which are slow twitch, and Type II, which are fast twitch. Depending on which you have more of, you may have an easier or harder time gaining muscle. “Fast twitch muscle fibers are two times as thick as slow twitch muscle fibers, lending to the overall thickness of the muscle without any activity,” explains Lovitt. “Those people with a genetic predisposition of a high percentage of these fibers can increase muscle size very easily while the people with a higher percentage of slow twitch muscle fibers have to work really hard to put on mass.” It’s the reason why a world-class sprinter genetically has more fast twitch muscle fibers than a world-class marathoner—it comes down to what we’re born with.
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.
Product reviews – Since the effectiveness of products varies based on a wide number of factors, one of the best things to do is read creatine product reviews. The best rated creatine products will have consistently good reviews, meaning a lot of people use that product and would recommend it. However – remember to take reviews with a grain of salt, as there’s a lot of ignorance and misinformation out there. 

One thing to keep in mind with this set is that it contains animal products from gelatin and milk. If you are vegan, do not consume these capsules. In terms of weight gain, it is important to note that these capsules do not contain calories. You need extra calories to gain weight. Above all, since this bulking stack requires you to take several pills daily, make sure to talk to your doctor before starting this supplement regimen.
Creatine is a hydrophilic polar molecule that consists of a negatively charged carboxyl group and a positively charged functional group [64]. The hydrophilic nature of creatine limits its bioavailability [65]. In an attempt to increase creatines bioavailability creatine has been esterified to reduce the hydrophilicity; this product is known as creatine ethyl ester. Manufacturers of creatine ethyl ester promote their product as being able to by-pass the creatine transporter due to improved sarcolemmal permeability toward creatine [65]. Spillane et al [65] analyzed the effects of a 5 days loading protocol (0.30 g/kg lean mass) followed by a 42 days maintenance phase (0.075 g/kg lean mass) of CM or ethyl ester both combined with a resistance training program in 30 novice males with no previous resistance training experience. The results of this study [65] showed that ethyl ester was not as effective as CM to enhance serum and muscle creatine stores. Furthermore creatine ethyl ester offered no additional benefit for improving body composition, muscle mass, strength, and power. This research did not support the claims of the creatine ethyl ester manufacturers.
Eat 0.4–0.5 grams of fat per pound of your body weight. Fat is essential for hormone optimization, brain function, and joint health. Now, if you’re following a ketogenic diet (or modified keto diet), or you just feel better with more fat in your diet, you can certainly add more fat and lower your protein and carb intake to accommodate it. The 0.4–0.5 grams per pound recommendation just represents a starting point and a minimum so that you don’t eat too little fat, either out of fear that it will make you fat or damage your heart (both untrue). For more about ketogenic diets, see Onnit’s guide HERE.
These complete proteins include all of the essential amino acids that the body cannot produce itself. Different proteins, such as whey and casein, egg and soy have different absorption rates. Whether you should favor one over another for muscle building is still a subject of popular and scientific debate, although whey protein isolate, a more rapidly absorbed protein, has some support from various scientific studies. For protein powders, assess the value by checking out the protein listed on the label. Combined with resistance training, sufficient protein consumption along with an appropriate diet can lead to increased muscle and reduced body fat. You should read more about The Bodybuilding Diet for supplement timing issues before and after training. 
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]
The reasons for differences in the effect of creatine on testosterone vs. DHT across studies are not clear, but also not mutually exclusive. A measured increase in DHT could indicate that testosterone levels were increased by creatine, but rapidly converted to DHT through a homeostatic mechanism. Differences in study subject populations, methodology, or the presence and type of concurrent exercise could also be contributing factors. At any rate, the literature collectively suggests that creatine has the general ability to cause a modest increase in androgen levels in men.

If you stop getting the results you want after several weeks of working out, it's time to mix things up. You need to challenge or "confuse" your muscles often to keep them growing. You can do this by putting a twist on your basic moves. Do a biceps curl with a reverse grip, for example. Or find a bench for the step-up move shown here. Change up your workout at least every 4 to 6 weeks for the best results.


Stash away your scale for several weeks — and set a strength training goal instead. That’s the advice of Lisette Cifaldi, director of behavioral health at Hilton Head Health weight loss resort who counsels patients. “I think strength training shifts your perspective,” she says. “The happiness doesn’t come from achieving a certain number [on the scale]. It comes from the process of getting stronger and feeling empowered that you’re navigating your own success.”
de Salles Painelli V, Alves VT, Ugrinowitsch C, et al. Creatine supplementation prevents acute strength loss induced by concurrent exercise. Eur J Appl Physiol 2014;114(8):1749-55.del Favero S, Roschel H, Artioli G, et al. Creatine but not betaine supplementation increases muscle phosphorylcreatine content and strength performance. Amino Acids 2012;42(6):2299-305. View abstract.
xEndurance’s Creatine-JB is a fantastic, all-natural creatine for athletes. It’s a little expensive at a dollar per serving, but it has a really pleasant citrus flavor and it contains a gram of lactate, which has been shown in some studies to improve time to exhaustion in short duration, high intensity workouts. It’s also third party tested by Labdoor and Informed Choice.

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.
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.
Men appear to have higher active creatine-kinase systems, and racial differences favor black people over hispanic people over white people in terms of the activity of the creatine-kinase system. This system is more variable in men, independent of supplementation. Exercise may increase the activity of the creatine-kinase system independent of supplementation. 
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