Creatine concentration is normally increased in the placenta and brain in the midgestation phase until term, with further increases in the brain for another two weeks after birth.[529] This effect appears to be due to the fetus itself expressing the creatine enzymes of synthesis (AGAT and GAMT) after 5% of the gestation time has passed (0.9 days in spiny mice).[529] Despite creatine normally suppressing AGAT when supplemented at high concentrations,[29][30] it appears that maternal supplementation of the diet with 5% creatine from the halfway point of pregnancy until term does not alter creatine synthesis in the newborn (no alterations in either AGAT or GAMT), nor does it affect the creatine transporter.[530] 
Health-food stores sell creatine supplements in capsule, chewable, and powdered form, the most popular being the powder. One teaspoon of powder contains 5 grams (g) of creatine monohydrate. The recommended daily dose is 1-2 teaspoons dissolved in 8 ounces of water or sweetened beverage. Manufacturers and distributors suggest a five- to seven-day loading phase with intake of 10-20 g (2-4 scoops) daily to fill up the muscle. The maintenance phase of 5-10 g/day is recommended before and/or immediately following a workout. This protocol is claimed to increase creatine muscle stores by 20-50%.
Rheumatoid arthritis. Early research shows that taking creatine by mouth daily increases lean muscle mass and may improve muscle strength, but does not improve physical functioning in adults with rheumatoid arthritis. In children, taking a specific supplement containing creatine and fatty acids twice daily for 30 days might reduce pain and swelling. But the effects of creatine alone are not clear.
Creatine supplementation appears to attenuate decreases in GLUT4 expression seen with immobility and may increase GLUT4 expression during exercise. While it seems capable of increasing GLUT4 during resting conditions, it has failed to reach significance, suggesting that creatine supplementation works best with some stimuli associated with exercise.
Creatine is an organic acid naturally occurring in the body that supplies energy to muscle cells for short bursts of energy (as required in lifting weights) via creatine phosphate replenishment of ATP. A number of scientific studies have shown that creatine can improve strength,[32] energy,[33] muscle mass, and recovery times. In addition, recent studies have also shown that creatine improves brain function.[34] and reduces mental fatigue.[35] Unlike steroids or other performance-enhancing drugs, creatine can be found naturally in many common foods such as herring, tuna, salmon, and beef.

This increased permeability is noted in glioma cells, where it exerts anti-cancer effects related to cell swelling,[99][100] and in other membranes, such as breast cancer cells[101] and skeletal (contractile) muscle cells.[102] The kinetics of cyclocreatine appear to be first-order,[101] with a relative Vmax of 90, Km of 25mM and a KD of 1.2mM.[103]
In fact, in one new study comparing the effects of aerobic exercise versus resistance training on the psychological health of obese adolescents, researchers found that people in the resistance group experienced significantly greater self-esteem and perceived strength over four weeks. But what’s most interesting is that the feeling of getting stronger — rather than any measurable gains — was all it took to give them a boost.
Mitochondrial myopathies are a subgroup of mitochondrial cytopathies in which the skeletal muscle is negatively influenced. They are characterized by weaknesses in muscular function and energy metabolism.[547] These particular myopathies are thought to benefit from creatine supplementation, since creatine can help with some of the dysregulated energy production.[548]
Bodybuilding became more popular in the 1950s and 1960s with the emergence of strength and gymnastics champions, and the simultaneous popularization of bodybuilding magazines, training principles, nutrition for bulking up and cutting down, the use of protein and other food supplements, and the opportunity to enter physique contests. The number of bodybuilding organizations grew, and most notably the International Federation of Bodybuilders (IFBB) was founded in 1946 by Canadian brothers Joe and Ben Weider. Other bodybuilding organizations included the Amateur Athletic Union (AAU), National Amateur Bodybuilding Association (NABBA), and the World Bodybuilding Guild (WBBG). Consequently, the male-dominated contests grew both in number and in size. Besides the many "Mr. XXX" (insert town, city, state, or region) championships, the most prestigious titles[according to whom?] were Mr. America, Mr. World, Mr. Universe, Mr. Galaxy, and ultimately Mr. Olympia, which was started in 1965 by the IFBB and is now considered the most important bodybuilding competition in the world.
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]

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] 
If you’re not lifting super-heavy weights, doing high-intensity workouts, or eating a mainly vegan or vegetarian diet, your body probably makes as much creatine as it needs. “Creatine is naturally found in animal-based products,” says Bates, “so your body can make plenty of creatine as long as you have a balanced diet that includes animal-based products.” Protein sources like beef, chicken, pork, and fish help your body produce the creatine it needs — it varies depending on the source, but, in general, a 3-ounce serving of meat will have about 0.4 grams (g) of creatine, Bates says. (6)
Skin degradation is caused by a loss of collagen and degradation of the extracellular matrix,[536] which is enhanced by UV radiation (produces reactive oxygen species which stimulate MMPs[537]) and contributes to skin integrity loss and wrinkling. Due to the stimulation of collagen being associated with a cellular surplus of energy[538] and intracellular stores of energy declining with age,[539][540] creatine has been investigated as a topical anti-aging agent. In vitro, creatine appears to be rapidly absorbed through the skin (52% within an hour, remaining similar at 3 hours) with most creatine found in the stratum corneum (79.6-86.5%) follwed by the epidermis (9-13.2%) and dermis (4.5-7.1%).[541] It is successful in stimulating collagen expression and procollagen secretion in fibroblasts, with the latter increasing to 449+/-204% of control.[541]
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]
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]

Change things up. After six or more weeks of consistent strength training, which is about the amount of time it takes to start seeing improvement in your body, you can change your routine to make it more difficult. Lifting the same weights for the same exercises every week will keep your body in the same place. You can modify weights or repetitions, choose different exercises, or change the order in which you do them. You only have to make one change at a time to make a difference, although more is often better. 
Creatine is found in many protein supplements at baseline in the form of creatine monohydrate. If you take a protein supplement, you may already be getting creatine. What makes this creatine so special? Like the protein supplement above, this creatine supplement contains no artificial sweeteners or dyes. It contains 5000mg of creatine per dose and includes certain compounds to increase the bioavailability of the creatine, allowing it to be better absorbed.
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.
One supplement, which a large body of research has proven effective in building muscle mass when combined with intensive strength training, is creatine (sold as creatine monohydrate). Creatine, a source of rapid energy, is stored in the muscles in small amounts. With creatine loading or supplementation, bodybuilders increase muscle stores of the energy-containing compound which then can be used to provide an extra boost for an intense-high-weight lifting session. Studies support that ingestion of a relatively high dose of creatine (20 to 30 grams per day for up to two weeks) increases muscle creatine stores by 10 to 30 percent and can boost muscle strength by about 10 percent when compared with resistance training alone (Rawson & Volek, 2003). Some athletes report (though research does not necessarily support) muscle cramping in response after using creatine supplements.
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]
Higher percieved effort during heat (or due to elevations in body heat) are thought to be mediated by either the serotonergic system (suppresses performance)[388] or the dopaminergic system (enhances performance),[389][234] and creatine is thought to be involved in percieved effort during heat training since it has been noted previously to interact with neurotransmission by enhancing both serotonergic[253] and dopaminergic[230] neurotransmission.
These supplements can vary considerably from product to product in ingredients, serving sizes, and more. But the goal of each of them is generally quite similar. Most bodybuilding supplements are designed to help stimulate new muscle growth, cut away excess fat, and improve the recovery process so that you can get the most out of each trip to the gym.
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.
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] 

If there are any benefits for swimming performance from creatine supplementation, they appear to be limited to a 50 meter sprint or a handful of 50 meter sprints with short intermissions. Excessive sprinting (over six sprints with short breaks) or too long of a break (five minutes rather than two) seem to not be associated with the benefits of creatine supplementation.
Creatine is known to be present in the retina due to the expression of creatine kinase (CK)[466][39] and the GAMT enzyme of creatine synthesis, which is also present in the mammalian retina.[467] Creatine in the blood can be transported into the retina via the creatine transporter (confirmed in humans[468]), and inhibiting transporter activity (by depleting the medium of chloride and sodium) reduces uptake by 80%.[469] The fact that not all uptake was inhibited suggests that another transporter, such as the monocarboxylate transporter MCT12 (or SLC16A12),[470] plays a role, perhaps moreso in the lens, where its levels were comparable to that of the major creatine transporter SLC6A8.[470] 
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]

Contrary to certain rumors that animal-based protein is more suitable to trigger muscle growth than plant-based protein, a study by Mangano et al. (2017) could not provide any evidence for this. In contrast, if combined properly, plant-based protein can even have a higher biological quality. A combination of one part wheat protein (e.g. seitan) and two parts soy protein (e.g. tofu) has thus been favored by many bodybuilders. Some bodybuilders, such as Patrik Baboumian and Robert Cheeke, follow a strict vegan diet.[37]

There are several different available forms of creatine: creatine anhydrous which is creatine with the water molecule removed in order to increase the concentration of creatine to a greater amount than that found in CM. Creatine has been manufactured in salt form: creatine pyruvate, creatine citrate, creatine malate, creatine phosphate, magnesium creatine, creatine oroate, Kre Alkalyn (creatine with baking soda). Creatine can also be manufactured in an ester form. Creatine ethyl ester (hydrochloride) is an example of this, as is creatine gluconate which is creatine bound to glucose. Another form is creatine effervescent which is creatine citrate or CM with citric acid and bicarbonate. The citric acid and bicarbonate react to produce an effervescent effect. When mixed with water the creatine separates from its carrier leaving a neutrally charged creatine, allowing it to dissolve to a higher degree in water. Manufacturers claim that creatine effervescent has a longer and more stable life in solution. When di-creatine citrate effervescent was studied [59] for stability in solution it was found that the di-creatine citrate dissociates to citric acid and creatine in aqueous solutions which in turn forms CM and eventually crystallises out of the solution due to its low solubility. Some of the creatine may also convert to creatinine.

Most experts recommend starting with your larger muscle groups and then proceeding to the smaller ones. The most demanding exercises are those performed by your large muscle groups, and you will need your smaller muscles to get the most out of these exercises. But don't feel limited by that. You can do your exercises in any order you like, and changing the order is a great way to challenge yourself in different ways.
Researchers described the study as one of the first to examine how strength training can reduce the risk of cardiovascular disease, separate from the effects of aerobic activity like running or long walks. The point: for those who are not meeting recommended guidelines for aerobic activity—perhaps because they lack the time—bursts of weight training can be enough.
Studies with animal and cellular models demonstrated positive effect of creatine ingestion on neurodegenerative diseases. These effects have been attributed to improved overall cellular bioenergetics due to an expansion of the phosphocreatine pool [50]. Creatine deficiency syndromes, due to deficiency of glycine amidinotransferase and guanidinoacetate methyltransferase, can cause decreases or complete absence of creatine in the central nervous system. Syndromes of this nature have the possibility to be improved by supplementing orally with creatine. Brain creatine deficiency resulting from ineffective crea T1 has been shown not to be effectively treated with oral creatine supplementation [51]. Additionally, oral creatine administration in patients with myopathies has shown conflicting results depending on the type of myopathy and creatine transport systems disorders [4].

In females, the combination of SSRIs (to increase serotonin levels in the synapse between neurons) and creatine shows promise in augmenting the anti-depressive effects of SSRI therapy[230]. Another pilot study conducted on depression and females showed efficacy of creatine supplementation.[231] The one study measuring male subjects noted an increase in mood and minimal anti-depressive effects, but it is not know whether this is due to gender differences or the model studies (post-traumatic stress disorder).[232]
According to, adenosine triphosphate (ATP) is made up of a nucleotide bonded to three phosphate groups. When one of those phosphate groups is cleaved from the ATP molecule, a lot of energy is made available. That energy is used to fuel chemical reactions in cells, and ATP becomes adenosine diphosphate (ADP). Creatine enables the release of energy from stored ATP and is converted to creatinine.
In fact, in one new study comparing the effects of aerobic exercise versus resistance training on the psychological health of obese adolescents, researchers found that people in the resistance group experienced significantly greater self-esteem and perceived strength over four weeks. But what’s most interesting is that the feeling of getting stronger — rather than any measurable gains — was all it took to give them a boost.
When looking specifically at human studies, there has been a failure of creatine supplementation to induce or exacerbate kidney damage in people with amyotrophic lateral sclerosis (ALS). Subjects do not experience kidney damage for up to or over a year’s worth of supplementation in the 5-10g range.[505][506][507] Postmenopausal women,[517] people with type II diabetes,[518] people on hemodialysis,[313] otherwise healthy elderly,[519] young people,[454][520][521] and athletes do not experience kidney damage either.[324] Moreover, numerous scientific reviews on both the long- and short-term safety of supplemental creatine have consistently found no adverse effects on kidney function in a wide range of doses.[522][523][524][452][525][451][526][527] However, while doses >10 g/day have been found not to impair kidney function, there are fewer long-term trials using such high chronic daily intakes.[527]
Spero Karas, MD, assistant professor of orthopaedics in the division of sports medicine at Emory University, says that testosterone, the male hormone responsible for muscle growth, maxes out between the ages of 16 and 18. It reaches a plateau during the 20s and then begins to decline. As a result, muscle building after the adolescent years can be challenging, he says.
Creatine supplementation has once been noted to improve wellbeing and fatigue resistance in people with DM2, but has twice failed for people with DM1. In all three studies, it has failed to improve power output. This is thought to be due to a reduction in the expression of the creatine transporter preventing an increase in muscular phosphocreatine content.
Knowledge – When it comes to building the best physique possible, you have to be willing to experiment and learn from your body. No one will be able to tell you what’s the most effective nutrition or training split for your individual genotype. Not only that, they don’t know your personal preference, injury history, asymmetries, experience level, or current work capacity.
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] 
A quantitative, comprehensive scientific summary and view of knowledge up to 2007 on the effects of creatine supplementation in athletes and active people was published in a 100 citation review position paper by the International Society of Sports Nutrition[5]. More recent literature has provided greater insight into the anabolic/performance enhancing mechanisms of creatine supplementation [15,25] suggesting that these effects may be due to satellite cell proliferation, myogenic transcription factors and insulin-like growth factor-1 signalling [16]. Saremi et al [26] reported a change in myogenic transcription factors when creatine supplementation and resistance training are combined in young healthy males. It was found that serum levels of myostatin, a muscle growth inhibitor, were decreased in the creatine group.
Osteoblast cells are known to express creatine kinase.[39][417] Bone growth factors such as IGF-1,[418] PTH,[419] and even Vitamin D[420][421] seem to induce bone growth alongside increases in creatine kinase activity. Vitamin D has been noted to work indirectly by increasing the cellular energy state (these hormones increase creatine kinase in order to do so) in order to make bone cells more responsive to estrogen.[420] This evidence, paired with enhanced growth rates of osteoblasts in the presence of higher than normal (10-20mM) concentrations of creatine[422] suggest a role of creatine in promoting osteoblastic and bone growth, secondary to increasing energy availability.

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.

If you’re a beginner, you should train with three full-body workouts per week. In each one, do a compound pushing movement (like a bench press), a compound pulling movement (like a chinup), and a compound lower-body exercise (squat, trap-bar deadlift, for example). If you want to add in 1–2 other exercises like loaded carries or kettlebell swings as a finisher, that’s fine, but three exercises is enough to work the whole body.

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]