Minor liver lesions (grade I, no grade II or III, pathology not indicative of toxicity) have been studied in SOD1 G93A transgenic mice (a research model for amyotrophic lateral sclerosis or ALS, but used in this study to assess a state of chronic pro-oxidative stress) for 159 days with 2% of feed intake and in CD-1 rats (seen as normal) over 56 days with 0.025-0.5mg/kg in CD-1 mice, although in Sprague-Dawley rats (normal controls) there were no significant differences noted even after 2% of feed intake for 365 days.[503] These observations appear to be due to the strain of the rodents used,[504][503] and human studies on amyotrophic lateral sclerosis (ALS; what the SOD1 G93A transgenic mice are thought to represent) lasting from nine to sixteen months with subjects supplementing with up to 10g of creatine daily have failed to find any abnormalities in serum biomarkers of liver or kidney health.[505][506][507]
Although creatine can be bought commercially as a standalone product it is often found in combination with other nutrients. A prime example is the combination of creatine with carbohydrate or protein and carbohydrate for augmenting creatine muscle retention [5] mediated through an insulin response from the pancreas [69]. Steenge et al [70] found that body creatine retention of 5 g CM was increased by 25% with the addition of 50 g of protein and 47 g of carbohydrate or 96 g carbohydrate when compared to a placebo treatment of 5 g carbohydrate. The addition of 10g of creatine to 75 g of dextrose, 2 g of taurine, vitamins and minerals, induced a change in cellular osmolarity which in addition to the expected increase in body mass, seems to produce an up regulation of large scale gene expression (mRNA content of genes and protein content of kinases involved in osmosensing and signal transduction, cytoskeleton remodelling, protein and glycogen synthesis regulation, satellite cell proliferation and differentiation, DNA replication and repair, RNA transcription control, and cell survival) [25]. Similar findings have also been reported for creatine monohydrate supplementation alone when combined with resistance training [71].

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]


The materials and information provided in this presentation, document and/or any other communication (“Communication”) from Onnit Labs, Inc. or any related entity or person (collectively “Onnit”) are strictly for informational purposes only and are not intended for use as diagnosis, prevention or treatment of a health problem or as a substitute for consulting a qualified medical professional. Some of the concepts presented herein may be theoretical.

One study demonstrated that daily supplementation with 5 g of creatine monohydrate increased the intracellular creatine and PCr content of quadriceps muscle in 17 human subjects. Those with the lowest initial total creatine content had the greatest increase. In addition, exercise enhanced creatine uptake in muscle. No adverse effects were reported [5].


A child’s ability to regenerate high energy phosphates during high intensity exercise is less than that of an adult. Due to this, creatine supplementation may benefit the rate and use of creatine phosphate and ATP rephosporylation. However, performance in short duration high-intensity exercise can be improved through training therefore supplementation may not be necessary [54].
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]

A loading phase of 10g creatine monohydrate for two weeks and 4g for the final week in subjects with MELAS (Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes) has been noted to increase physical strength relative to baseline, although the poor VO2 max seen in these subjects was not affected.[549] A case study exists in which a patient with a relatively novel mutation in their mitochondrial function (affecting cytochrome B) experienced benefits from creatine at 10g daily.[550] Researchers examining another case of MELAS found both cognitive and physical benefits with 5g creatine supplementation,[551] while four controlled case studies of 100-200mg/kg daily in children with myopathies found improved muscular endurance (30-57%) and muscular power (8-17%) after 100-200mg/kg daily for at least three months.[552]
A muscle imbalance—when one muscle is stronger than its opposing muscle—can limit your ability to exercise effectively, and could lead to injury down the line. “It’s important to recognize whether you’re really working the muscles you think you are and recognize if you’ve developed an imbalance that alters your movement pattern,” says Eric Ingram, physical therapist at Louisiana Physical Therapy Centers of Pineville. One common imbalance in women is stronger quads and weaker, tighter hamstrings, thanks to prolonged sitting, high heels, and improper training. If you suspect you have a muscle imbalance, make an appointment with a physical therapist, who will prescribe exercises to even you out.
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.
So, for example, with the moves above you'd do 15 squats followed by 15 push-ups. Take a little breather then repeat that two more times. Then you move on to your walking lunges and lat pull-downs (and repeat those three times total, too). You can really do anywhere from eight reps to 15 (and even just two sets, if you don't have time for three), but "it’s not a bad idea for beginners to start with a 15-rep range to get comfortable with the exercises," says Davis. And while there's some debate over whether three sets of an exercise is really best, "it’s a great beginner model," says Davis. Don't overcomplicate things when you're just getting started.

Bodybuilders do cardio training such as running and using a StairMaster StepMill to burn fat and make their muscles more visible. “Do cardio throughout the year at least three days a week for at least 30-40 minutes, whether it be first thing in the morning on an empty stomach or after a post-workout protein shake,” says Heath. “Cardio won’t kill your gains as much as you think, you’ll see how much muscle you really have.” Break a sweat to stay lean ’round the clock.
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] 

Perform the two workouts (Day 1 and 2) once each per week, resting at least a day between each. Perform the exercises marked with letters as a group. Do one set of A, rest, then one set of B, rest (note that some groups have an exercise “C”), and repeat until all sets are complete. Then go on to the next group. Perform three sets of 8–10 reps for each exercise. After a month, you’ll see how rewarding just a months in the gym can be.
The first published results (not blinded) noted that a loading phase of 20g of creatine for a week, followed by 3g daily for up to six months, was able to enhance maximal voluntary isometric muscular contraction (MVIC) on a dynamometer for both the knee and elbow joints, with enhanced fatigue resistance on the same joints in more than half of subjects (53-70% response rate).[545]
Pro Tip: Zane also suggests that directed concentration is exceptionally important to getting the most from your training and is much easier with lower weight. If you can concentrate on the muscle through its whole movement, you will notice that the intensity will be just as strong, without the risk. We teach you this in our “Mind Muscle Connection” Bonus Guide that we include in our Old School Muscle 8-Week Program.

If you’re exercising at your maximum intensity, your body literally can’t produce enough ATP to keep up. (10) That’s where creatine supplements come in: They can help increase your body’s stores of phosphocreatine (an organic compound of creatine and phosphoric acid that’s stored in your muscle tissue) to produce new ATP during high-intensity exercise.
Nephrotoxic drugs. Because taking high doses of creatine might harm your kidneys, there is concern about combining creatine with drugs that might damage the kidneys (nephrotoxic drugs). Potentially nephrotoxic drugs include nonsteroidal anti-inflammatory drug (NSAIDs) such as ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve, others), cyclosporine (Neoral, Sandimmune) and others.
Squats target both your inner and outer thighs. Use a barbell heavy enough to challenge your muscles but light enough that you can still control your form. Hold it behind your head with your feet shoulder-width apart. Tighten your core, then squat down as far as comfortable. There should be no knee or back pain. As you come back up, raise your hips and chest together.

Warm up sets are also important. For example, the same lifter working on his chest would also be advised to complete at least two warm up sets prior to hitting his "core tonnage." Core tonnage refers to the heavier lifts that actually strain your muscles. For example, if the lifter's main sets were at 205 lbs, 225 lbs and 235 lbs on the bench, then a warmup of 5 reps of 135 and 5 reps of 185 would be advisable. Some lifters will warm up with a 50/50 set for example 50% of the target weight for 50% of the target repetitions. When properly warmed up the lifter will then have more strength and stamina since the blood has begun to flow to the muscle groups.[7]
Bodybuilding developed in the late 19th century, promoted in England by German Eugen Sandow, now considered as the "Father of Bodybuilding". He allowed audiences to enjoy viewing his physique in "muscle display performances". Although audiences were thrilled to see a well-developed physique, the men simply displayed their bodies as part of strength demonstrations or wrestling matches. Sandow had a stage show built around these displays through his manager, Florenz Ziegfeld. The Oscar-winning 1936 musical film The Great Ziegfeld depicts the beginning of modern bodybuilding, when Sandow began to display his body for carnivals.
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.
Glutamine and beta-alanine are amino acids and HMB, beta-hydroxy-beta-methyl butyrate, is a byproduct of leucine, another amino acid. Promoting individual amino acids, the building blocks of protein, to enhance performance in the strength sports has been a particular focus of supplement manufacturers over the years. To date, the evidence for any advantage has been mixed and mostly unimpressive.

The creatine transporter (CrT) is positively regulated by proteins known to be involved in sensing and responding to the cellular energy state, including the mammalian target of rapamycin (mTOR[158]). Upon activation, mTOR stimulates SGK1 and SGK3[159][160] to act upon PIKfyve[161] and subsequently PI(3,5)P2[162] to increase CrT activity.[161] Beyond mTOR, SGK1 also is stimulated by intracellular calcium[163] and a lack of oxygen (ischemia).[164] Because transient ischemia is associated with increased reactive oxygen species (ROS) production after blood flow is restored (reperfusion) it has been hypothesized that muscle contraction may increase creatine uptake through a similar ROS-mediated mechanism.[165]
One of the studies noting a reduction in fatigue in healthy subjects given creatine (8g) for five days prior to a mathematical test noted a relative decrease in oxygenation hemoglobin in the brain and an increase in deoxygenated hemoglobin, which normally indicates a reduction in cerebral oxygenation.[245] The authors made note of how cytoplasmic phosphocreatine can increase oxygen uptake into cells (noted in vitro in a concentration dependent manner between 0-25mM[245]) and suggested that either cells were taking up more oxygen from hemoglobin, or that increased mitochondrial efficiency resulted in less of a need for oxygen.[245]
Who Makes It: This product is made by Cellucor, a sports and fitness supplement firm best-known for their C4 line of pre-workout supplements. While C4 is their best seller (and a top seller overall), Cellucor also manufactures a wide range of high-quality supplements for a variety of uses. They have been in business for over 15 years and are a trusted name in the fitness community.
Bryant, a lawyer and sports agent, opened a case of manila file folders and spread them on the desk like playing cards. Each was labeled: Phil Heath Enterprises, Sponsors, Taxes, Travel and so on. Bryant, Heath and Cremona discussed Heath’s clothing line and his sponsorships. They talked about his desire for a shoe deal and a larger hyperbaric chamber at his house.
Natalie Digate Muth, MD, MPH, RD, is the ACE senior consultant for healthcare solutions, a practicing pediatrician and registered dietitian. Recognized as a Certified Obesity Specialist, Natalie has written for more than 50 publications and, in 2012, published her first book, 'Eat Your Vegetables' and Other Mistakes Parents Make: Redefining How to Raise Healthy Eaters.
Cornelissen, V. A., Defoor, J. G., Stevens, A., Schepers, D., Hespel, P., Decramer, M., Mortelmans, L., Dobbels, F., Vanhaecke, J., Fagard, R. H., and Vanhees, L. Effect of creatine supplementation as a potential adjuvant therapy to exercise training in cardiac patients: a randomized controlled trial. Clin.Rehabil. 2010;24(11):988-999. View abstract.

When it comes to building lean muscle, size bodybuilders are king. That’s their ultimate goal. Sure, Crossfit, powerlifting and all the other modalities will build muscle, but that’s not their focus. They want performance and any muscle they build is a side effect. Not so with bodybuilding where muscle size and shape are the priorities. Learning how to build muscle for the sake of building muscle has some benefits to the performance athlete. It allows for ais less injury prone. Its also a fact that bigger muscle contract harder regardless of technique or form, so it’s a good strategy to throw in some bodybuilder muscle building sessions here and there to give yourself stronger muscles to then train for performance. Build the muscle bigger, then train it to perform better.


You are encouraged to confirm information obtained from or through this website with other sources. Our content is not a substitute for qualified medical advice. The supplement summaries on this website may not include all the information pertinent to your use. Before starting a diet, taking new supplements, or beginning an exercise program, check with your doctor to clear any lifestyle changes. Only your doctor can determine what is right for you based on your medical history and prescriptions.
^ Jump up to: a b c d e Cooper R, Naclerio F, Allgrove J, Jimenez A (July 2012). "Creatine supplementation with specific view to exercise/sports performance: an update". Journal of the International Society of Sports Nutrition. 9 (1): 33. doi:10.1186/1550-2783-9-33. PMC 3407788. PMID 22817979. Creatine is produced endogenously at an amount of about 1 g/d. Synthesis predominately occurs in the liver, kidneys, and to a lesser extent in the pancreas. The remainder of the creatine available to the body is obtained through the diet at about 1 g/d for an omnivorous diet. 95% of the bodies creatine stores are found in the skeletal muscle and the remaining 5% is distributed in the brain, liver, kidney, and testes [1].
You don’t have to, but you can. The typical creatine dose is 5 grams once or twice per day, but it’s sometimes suggested that one should “load” creatine by taking 20 to 25 grams per day for the first week of usage. This is then followed with 3 to 4 weeks of 5 grams per day, then a break for a week or two, then repeat. This may bring about more acute increases in strength and muscle size — creatine will “work” more quickly, in other words — but it’s not necessary.

Kerksick, C. M., Wilborn, C. D., Campbell, W. I., Harvey, T. M., Marcello, B. M., Roberts, M. D., Parker, A. G., Byars, A. G., Greenwood, L. D., Almada, A. L., Kreider, R. B., and Greenwood, M. The effects of creatine monohydrate supplementation with and without D-pinitol on resistance training adaptations. J.Strength.Cond.Res. 2009;23(9):2673-2682. View abstract.
As mentioned earlier, supplementation of creatine in youth has been noted to improve the swim bench test (a thirty second sprint followed by another after a five minute break).[398] One study noted improvement when examining a 400 meter test after 10g of creatine was taken over seven days with some orange juice. The improvement was mostly attributable to increased performance on the last 50m stretch.[405]

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.


Creatine is only taken up by its transporter, and changes in the activity level of this transporter are wholly causative of changes in creatine uptake. The transporter is regulated by mostly cytosolic factors as well as some external factors that affect creatine transport activity, [143] including extracellular creatine.[140] Agents affecting creatine transport are further divided into positive regulators (those that increase activity of the transporter) and negative regulators (those that suppress activity).
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.

McArdle’s disease is a myopathic disorder associated with fatigue and contractile dysfunction as a result of alterations in the release of glucose from glycogen (via defects in myophosphorylase enzyme function) resulting in an inability to conduct high intensity work as easily.[548] Creatine is thought to be therapeutic because beyond the general strength enhancing properties of creatine, people with McArdle’s disease have an upregulation of phosphofructokinase (PFK) enzyme activity [570] and increasing phosphocreatine storages suppresses the activity of this enzyme.[571]
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]

This concept of timing has been applied to everything from fat burners, protein supplements, carbohydrates, and various other supplements. In some cases, you can see a difference based on when you take a product. But more often, the timing is based more on anecdotal evidence than any hard science. Recently, this nutrient timing aspect has even been extended to creatine, a product that is so effective that it’s worth the investigation of determining if there’s an element that can give you even greater benefits.
In regard to the blood brain barrier (BBB), which is a tightly woven mesh of non-fenestrated microcapillary endothelial cells (MCECs) that prevents passive diffusion of many water-soluble or large compounds into the brain, creatine can be taken into the brain via the SLC6A8 transporter.[192] In contrast, the creatine precursor (guanidinoacetate, or GAA) only appears to enter this transporter during creatine deficiency.[192] More creatine is taken up than effluxed, and more GAA is effluxed rather than taken up, suggesting that creatine utilization in the brain from blood-borne sources[192] is the major source of neural creatine.[193][192] However, “capable of passage” differs from “unregulated passage” and creatine appears to have tightly regulated entry into the brain in vivo[193]. After injecting rats with a large dose of creatine, creatine levels increased and plateaued at 70uM above baseline levels. These baseline levels are about 10mM, so this equates to an 0.7% increase when superloaded.[193] These kinetics may be a reason for the relative lack of neural effects of creatine supplementation in creatine sufficient populations.
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