The creatine kinase system appears to be detectable in endothelial cells.[314][315] Under basal conditions, creatine itself is expressed at around 2.85+/-0.62μM[316] (three-fold higher than HUVEC cells[314]). When incubating the medium with 0.5mM creatine, endothelial cells can take up creatine via the creatine transporter (SLC6A8) and increase both creatine (almost doubling) and phosphocreatine (nearly 2.5-fold) concentrations.[316]

Finally, starvation (nutrient deprivation for four days) appears to increase activity of the creatine transporter secondary to decreasing serine phosphorylation (SGK target)[173] with no influence on tyrosine phosphorylation (c-Src target).[173] Starvation-induced increases in creatine influx do not necessarily mean more phosphocreatine, however, due to a depleted cellular energy state.[173]
1. Are you tracking calories? Doesn't have to be religiously but one should have a general idea of where they're at if the goal is mass gain and things have stalled. I'm not talking about weighing every gram of food you put in your mouth and meticulously logging your life on MyFitnessPal. As long as you're aware (within 100-200 calories) of what's going in, you should have an idea of what to adjust.
Cooke et al [41] observed positive effects of a prior (0.3 g/d kg BW) loading and a post maintenance protocol (0.1 g/d kg BW) to attenuate the loss of strength and muscle damage after an acute supramaximal (3 set x 10 rep with 120% 1RM) eccentric resistance training session in young males. The authors speculate that creatine ingestion prior to exercise may enhance calcium buffering capacity of the muscle and reduce calcium-activated proteases which in turn minimize sarcolemma and further influxes of calcium into the muscle. In addition creatine ingestion post exercise would enhance regenerative responses, favoring a more anabolic environment to avoid severe muscle damage and improve the recovery process. In addition, in vitro studies have demonstrated the antioxidant effects of creatine to remove superoxide anion radicals and peroxinitrite radicals [42]. This antioxidant effect of creatine has been associated with the presence of Arginine in its molecule. Arginine is also a substrate for nitric oxide synthesis and can increase the production of nitric oxide which has higher vasodilatation properties, and acts as a free radical that modulates metabolism, contractibility and glucose uptake in skeletal muscle. Other amino acids contained in the creatine molecule such as glycine and methinine may be especially susceptible to free radical oxidation because of sulfhydryl groups [42]. A more recent in vitro study showed that creatine exerts direct antioxidant activity via a scavenging mechanism in oxidatively injured cultured mammalian cells [43]. In a recent in vivo study Rhaini et al [44] showed a positive effect of 7 days of creatine supplementation (4 x 5 g CM 20 g total) on 27 recreational resistance trained males to attenuate the oxidation of DNA and lipid peroxidation after a strenuous resistance training protocol.
Heath suggests incorporating dropsets into your training routine by immediately decreasing the weight and repping out again to failure. “Dropsets overload the muscle with shorter rest periods and increasing volume which you need to grow,” says Heath. “That overload improves your body’s abilities to utilize more nutrients, natural growth hormone, and natural testosterone into those areas and makes the supplements you take more effective.” Heath’s favorite way to do dropsets is on a pin-loaded machine since it’s faster to switch weights.
In regard to bioenergetics, phosphorylated cyclocreatine appears to have less affinity for the creatine kinase enzyme than phosphorylated creatine in terms of donating the high energy phosphate group (about 160-fold less affinity) despite the process of receiving phosphorylation being similar.[104][105] When fed to chickens, phosphorylated cyclocreatine can accumulate up to 60mM in skeletal muscle,[106] which suggests a sequestering of phosphate groups before equilibrium is reached.[105] Cyclocreatine still has the capacity to donate phosphate, however, as beta-adrenergic stimulated skeletal muscle (which depletes ATP and glycogen) exhibits an attenuation of glycogen depletion (indicative of preservation of ATP) with phosphocreatine.[102]
Bodybuilders spend years and years of their lives focused on perfecting the human body through proper training and nutrition. You, on the other hand, might not have an interest in the sport of bodybuilding, but do want to know the secrets to six-pack abs, a wide back, and rounded shoulders. And what better place to score the tricks of the trade than from 3-time Mr. Olympia Phil Heath. 

Due to this relative deficiency-state in vegetarians and vegans, some aspects of creatine supplementation are seen as more akin to normalizing a deficiency, rather than providing the benefits of supplementation. In young vegetarians, but not omnivores, creatine supplementation can enhance cognition.[60][61] The increased gain in lean mass may be more significant in vegetarians, relative to omnivores.[59] Supplementation of creatine in vegetarians appears to normalize the gap in storage between vegetarians and omnivores.[62] This is possibly related to a correlation seen in survey research, where vegetarianism and veganism appear to be more commonly affected by some mental disorders like anxiety and depression.[63]


The bulking and cutting strategy is effective because there is a well-established link between muscle hypertrophy and being in a state of positive energy balance.[19] A sustained period of caloric surplus will allow the athlete to gain more fat-free mass than they could otherwise gain under eucaloric conditions. Some gain in fat mass is expected, which athletes seek to oxidize in a cutting period while maintaining as much lean mass as possible.
The best way to know the real progress you’re making is by recording it on video or taking photos. “Photos mean everything because if you can take them in the same areas and in the same poses, you’ll see your strengths and weaknesses clearly,” says Heath. “Revise your training and diet programs to eliminate weaknesses.” Keep a file of your progress to see just how far you can take your fitness.
There are many camps within the weight training fitness community. We have bodybuilders, Crossfit athletes, powerlifters, Olympic lifters, and strongman athletes just to name the most popular ones off the top of my head. One thing they all have in common is that they all use resistance to achieve a particular goal. They all also “share” particular exercises. Most resistance-training athletes do barbell squats, overhead presses and deadlifts. I can write pages of differences between each of the disciplines I listed above and I can also write quite a bit about their similarities but one form of resistance training is MORE different than the others. Bodybuilding is the only sport that judges the appearance of the athlete rather than their performance. This may be why bodybuilders tend to get poked at the most.
Legion’s Recharge is a good pick for muscle growth. Besides the creatine itself, it contains a hefty 2.1 grams of l-carnitine l-tartrate, which has solid links with improving muscle repair in addition to increasing focus during workouts. It’s also delicious, naturally sweetened, and it contains ingredients that may improve insulin sensitivity and help the body to better utilize carbs for recovery.
There is a genetic condition known as gyrate atrophy of the choroid and retina, which is associated with a high level of Ornithine in the blood and a relative decrease in Arginine, which causes a relative creatine deficiency due to L-arginine being required to make creatine[478][479] and because high ornithine can suppress creatine synthesis (AGAT) in the glial cells of the retina.[475] This condition can be attenuated by either reducting ornithine in the diet[480] or by supplementing creatine, which is, in this instance, therapeutic.[481][482]
Taking creatine supplements may increase the amount of creatine in the muscles. Muscles may be able to generate more energy or generate energy at a faster rate. Some people think that taking creatine supplements along with training will improve performance by providing quick bursts of intense energy for activities such as sprinting and weightlifting.
When you’re planning your high-protein meals, 20 grams of protein is the optimal amount generally accepted for muscle growth. Research has found that the body doesn’t use much more than 20 grams for muscle-building at any one sitting. Around 80 grams of protein per day (or, four meals containing 20-grams of protein each) is about right for most people.

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.

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!
Beast Creature could be another good option for female athletes. It’s tasty, it contains five types of creatine, and it contains ingredients that could improve fat loss by increasing insulin sensitivity. One potential bonus is that it also has 70 percent of your daily biotin, a nutrient often included in women’s multivitamins due its purported benefits for hair and nails.
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.
Creatine ethyl ester increases muscle levels of creatine to a lesser degree than creatine monohydrate.[72] It may also result in higher serum creatinine levels[73] due to creatine ethyl ester being converted into creatinine via non-enzymatic means in an environment similar to the digestive tract.[74][75] At equal doses to creatine monohydrate, ethyl ester has failed to increase water weight after 28 days of administration (indicative of muscle deposition rates of creatine, which are seemingly absent with ethyl ester).[76] 

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]
It may seem odd to put such a common supplement as minerals on this list, but few people are aware that minerals are enzyme activators. Many vitamins, on the other hand, are coenzymes, which means that without minerals they're useless. Many minerals, such as zinc and chromium, also interact with various anabolic hormones, such as testosterone, growth hormone and insulin.

Sound complicated? Fortunately, there's an easy rule of thumb for increasing your training volume: For each exercise, perform three to six sets of six to 12 reps, resting for 30 to 90 seconds between each set, she says. The weight used should be enough that you can get out your last reps with proper form but wouldn't be able to perform any additional reps.


Amanda is a Registered Dietitian Nutritionist in Chicago who graduated with a bachelor's in Nutrition from Northern Illinois University. She completed her dietetic internship at Edward Hines Jr. VA Hospital in Hines, IL. Amanda has a strong background in clinical nutrition, nutrition education, and experience working with specialized populations like children, acute care, intensive care, outpatients, and eating disorders. Amanda works with athletes and weight loss clients in the Los Angeles and southwestern Arizona area as a virtual Dietitian. Amanda prides herself in connecting with her audience while providing evidenced-based information and practical nutrition therapy for a complex population.
The harder an exercise is – both in terms of technicality and physical/mental demand – the more rest there should usually be. So exercises like squats and deadlifts should have more rest between sets than exercises like leg extensions and leg curls. And exercises like various bench presses, shoulder presses, rows and pull-ups should have more rest between sets than bicep curls, tricep extensions, chest flies and lateral raises.
If you’re new to training, then check out some of the options found on the site and run them exactly as the author intended them to be executed. Too many young guns want to alter every training variable rather than running the program as written and focusing on getting stronger. No, you don’t need an entire day dedicated to arms when you can’t even complete a single chin-up.
Wilkinson, S. B., Tarnopolsky, M. A., MacDonald, M. J., MacDonald, J. R., Armstrong, D., & Phillips, S. M. (2007). Consumption of fluid skim milk promotes greater muscle protein accretion after resistance exercise than does consumption of an isonitrogenous and isoenergetic soy-protein beverage. The American Journal of Clinical Nutrition, 85(4), 1031-1040.
As you've probably heard from any muscle-bound behemoth you've ever encountered, protein is the key to building muscle. Just because the shake-pounding meathead has become a trope, however, doesn't mean they're wrong; protein really is the fuel your muscles need to grow. That's real capital-S Science, not just bro-science manufactured by supplements companies.
A typical creatine supplementation protocol consists of a loading phase of 20 g CM/d or 0.3 g CM/kg/d split into 4 daily intakes of 5 g each, followed by a maintenance phase of 3-5 g CM/d or 0.03 g CM/kg/d for the duration of the supplementation period [5]. Other supplementation protocols are also used such as a daily single dose of around 3 – 6 g or between 0.03 to 0.1 g/kg/d [15,55] however this method takes longer (between 21 to 28 days) to produce ergogenic effects [5]. Sale et al [56] found that a moderate protocol consisting of 20 g CM taken in 1g doses (evenly ingested at 30-min intervals) for 5 days resulted in reduced urinary creatine and methylamine excretion, leading to an estimated increase in whole body retention of creatine (+13%) when compared with a typical loading supplementation protocol of 4 x 5 g/d during 5 days (evenly ingested at 3 hour intervals). This enhancement in creatine retention would lead to a significantly higher weight gain when people follow a moderate protocol ingestion of several doses of small amounts of CM evenly spread along the day.
No. It’s not easy for everyone to get the recommended amount of protein in their diets through good eating habits alone. Others may not have clinically low testosterone, but still benefit from boosting their levels to improve their muscle building capacity. You can fix these common problems through muscle building supplements. These easy to take pills and powders can also help you boost your performance at the gym which will, in turn, spur your body’s muscle building and recovery response.
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