When endothelial cells have a higher creatine concentration, they appear to be mildly less permeable when incubated with 0.5-5mM creatine, while the higher concentration (5mM) is able to fully ablate TNF-α-induced neutrophil adhesion and both E-selectin and ICAM-1 expression.[316] This effect was prevented with ZM241385, an A2A (adenosine) receptor antagonist,[316] and since adenosine released by this receptor is known to be protective of endothelial cells,[317][318] it is thought that creatine works vicariously through this receptor and adenosine release, thought to be due to releasing ATP (occurs in response to stress[319][320]) which protects the cell via the A2A signaling system.[316]

Creatine has been noted to increase the amplitude (0.5-5mM) and frequency (25mM only) of NMDA receptors, although concentrations of 0.5-25mM also reduced signaling intensity. This was credited to creatine causing an increase in ligand binding of glutamate with an EC50 of 67µM and maximal activity at 1mM creatine (158±16% of baseline).[214] Creatine appears to modulate the polyamine binding site of the NMDA receptor, as it is abolished by arcaine and potentiated by spermidine.[215] This binding site is known to modify NMDA receptor affinity.[216][217]
Similarly to complex training, contrast loading relies upon the enhanced activation of the nervous system and increased muscle fibre recruitment from the heavy set, to allow the lighter set to be performed more powerfully.[41] Such a physiological effect is commonly referred to as post-activation potentiation, or the PAP effect. Contrast loading can effectively demonstrate the PAP effect: if a light weight is lifted, and then a heavy weight is lifted, and then the same light weight is lifted again, then the light weight will feel lighter the second time it has been lifted. This is due to the enhanced PAP effect which occurs as a result of the heavy lift being utilised in the subsequent lighter lift; thus making the weight feel lighter and allowing the lift to be performed more powerfully.
This basic form of creatine comes in two forms, one of which involves the removal of the monohydrate (which results in creatine anhydrous) that converts to creatine monohydrate in an aqueous environment,[66][67] but due to the exclusion of the monohydrate it is 100% creatine by weight despite creatine monohydrate being 88% creatine by weight, as the monohydrate is 12%. This allows more creatine to be present in a concentrated formula, like capsules.[68]
One rat study that compared male and female rats and used a forced swim test (as a measure of serotonergic activity of anti-depressants[227]) found that a sexual dimorphism existed, and females exerted a serotonin-mediated anti-depressant response while male rats did not.[228] It appears that these anti-depressive effects are mediated via the 5-HT1A subset of serotonin receptors, as the antidepressant effects can be abolished by 5-HT1A inhibitors.[229]
The lower the rep range (and therefore the higher the intensity and the heavier the weight), the more rest there should be between sets. So most of the time, exercises being done in the 5-8 rep range need longer rest periods than exercises being done in the 8-10 rep range, which need longer rest periods than exercises being done in the 10-15 rep range.
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.
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.
It is suggested [16,37] that another mechanism for the effect of creatine could be enhanced muscle glycogen accumulation and GLUT4 expression, when creatine supplementation is combined with a glycogen depleting exercise. Whereas it has been observed [38] that creatine supplementation alone does not enhance muscle glycogen storage. Hickner et al [15] observed positive effects of creatine supplementation for enhancing initial and maintaining a higher level of muscle glycogen during 2 hours of cycling. In general, it is accepted that glycogen depleting exercises, such as high intensity or long duration exercise should combine high carbohydrate diets with creatine supplementation to achieve heightened muscle glycogen stores [39].
Cranking up the levels of testosterone within the body, XPI's Testosyn is formulated with 100% natural and powerful ingredients to build lean muscle, boost sex drive, and increase energy levels. Using a high-performance testosterone complex that contains D-Aspartic Acid, Fenusterols, and Tribulus Terrestris, this potent supplement will aid in the enhancement of each workout and promote free testosterone. Testosyn's ingredients have the ability to increase testosterone levels nearly twice as much as other products for more strength, mass, and sexual vigor. Keep Reading »
In regard to the loading period, two reviews suggest that the range of weight gain associated with creatine supplementation at 20g for 7 days is in the range of 0.9-1.8kg (1.98-3.96lbs).[612][613] The highest reported increase in water weight associated with creatine loading, although measured a month after loading started (after a maintenance phase) was 3.8kg (8.36lbs).[614]
All you need to know about low creatinine levels Creatinine is a waste material in the body, and low levels can suggest a shortfall in liver function or activity. This MNT Knowledge Center feature looks at low creatinine levels., as well as information on what creatinine is, how it affects the body, and how to increase low creatinine levels. Read now

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In otherwise sedentary and healthy men given a loading phase of creatine followed by 11 weeks of maintenance, the glucose response to an oral glucose tolerance test is reduced by 11-22% (measurements at 4-12 weeks with no time dependence noted) which was not associated with changes in insulin levels or sensitivity.[350] Elsewhere, a study in vegetarians (5g daily for 42 days) failed to find a reduction in postprandial blood glucose.[351]
Chwalbinska-Monteta [34] observed a significant decrease in blood lactate accumulation when exercising at lower intensities as well as an increase in lactate threshold in elite male endurance rowers after consuming a short loading (5 days 20 g/d) CM protocol. However, the effects of creatine supplementation on endurance performance have been questioned by some studies. Graef et al [35] examined the effects of four weeks of creatine citrate supplementation and high-intensity interval training on cardio respiratory fitness. A greater increase of the ventilatory threshold was observed in the creatine group respect to placebo; however, oxygen consumption showed no significant differences between the groups. The total work presented no interaction and no main effect for time for any of the groups. Thompson et al [36] reported no effects of a 6 week 2 g CM/d in aerobic and anaerobic endurance performance in female swimmers. In addition, of the concern related to the dosage used in these studies, it could be possible that the potential benefits of creatine supplementation on endurance performance were more related to effects of anaerobic threshold localization.
Still, any supplement should be used carefully and after discussion with a dietitian or doctor. There are some potential health risks and side effects that you should be aware of before taking creatine. Muscle cramping, nausea, diarrhea, dizziness, gastrointestinal pain, dehydration, weight gain, water retention, heat intolerance, and fever have all been linked to the supplement. (13)
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.
Eat healthy fats. That's right—not only does it make food taste good, fat is good for you, as long as you are eating the right kinds and amounts of fat! Saturated fats—the fat you'll find in a stick of butter, a bag of chips, or bacon—should be limited to about 20g or less. That's the bad news. The good news is that unsaturated fats are actually beneficial, even necessary. Fat is necessary for the proper distribution of vitamins A, D, E, and K, helps promote better eyesight, and healthy skin. Fats are also important for the synthesis of hormones, so maintaining an adequate intake of them will speed up muscle-building and recovery.
In October 1994, the Dietary Supplement Health and Education Act (DSHEA) was signed into law in the USA. Under DSHEA, responsibility for determining the safety of the dietary supplements changed from government to the manufacturer and supplements no longer required approval from the U.S. Food and Drug Administration (FDA) before distributing product. Since that time manufacturers did not have to provide FDA with the evidence to substantiate safety or effectiveness unless a new dietary ingredient was added. It is widely believed that the 1994 DSHEA further consolidated the position of the supplement industry and lead to additional product sales.[6]
Although research is underway, doctors do not know the long-term health effects of taking creatine supplements, especially in children who are still growing. Because of these unknown risks, children and adolescents younger than 18 years and pregnant or nursing women should never take creatine supplements. People with kidney problems also should never take creatine supplements.
Need the motivation to push past your comfort zone and squeeze out one more push-up or bicep curl? Sure, it helps to remember that you’ll get stronger, rock more toned muscles and rev your metabolism, thanks to all that added muscle mass. But if that wasn’t enough, now comes news that all that pump-itude (yes, that’s an SNL reference) has psychological benefits, too.
Once training is resumed under these conditions, there may be little in the way of caloric support to ensure that protein synthesis and muscle growth occurs. Muscle may even begin to cannibalize itself as the body enters into a catabolic state. Even with the best of diets this can sometimes happen if training demands override the nutritional balance or imbalance.

This is another thing I am very tired of hearing. 'No matter what I do or what I eat, I can't gain weight'. I have heard this countless times and I am here to tell you that you are dead wrong. That's OK, because I actually said the same thing until I realized the truth. Most people think they are eating a lot and you just may be. But no matter what you are eating, if you are not gaining, you are not eating enough. Most times, you should re-evaluate your diet as well and focus on more calorie dense foods. But you need to eat more if you are not gaining.

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. 

Kornblum, C., Schroder, R., Muller, K., Vorgerd, M., Eggers, J., Bogdanow, M., Papassotiropoulos, A., Fabian, K., Klockgether, T., and Zange, J. Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover study. Eur J Neurol 2005;12(4):300-309. View abstract.
One study lasting 16 months using 10g creatine daily alongside the pharmaceutical riluzole noted that, after 34 of the patients died from ALS, creatine failed to exert protective effects against ALS-related mortality (adjusted hazard ratio of 0.78 with a 95% CI of 0.47–1.48[505]). A smaller study measuring only eight deaths noted that the six in placebo (relative to two in creatine) was too small of a sample size to detect a statistically significant difference.[506] A nonsignificant trend to increase survival has been noted elsewhere with 5g of creatine daily with a similar ratio: 3 deaths in placebo to 1 death in creatine.[507]
Recently, studies are coming out that show a general decline in testosterone levels of men in the United States and around the world. The trend is across the board and doesn’t appear to be caused simply by a decline in health, aging or an increase in obesity rates. It could be caused because of chemicals or environmental factors. In any case, low levels of testosterone can affect many areas of your health, including your ability to build muscle. If you suspect that you have low testosterone levels, you can ask your doctor to test you for it. In addition to traditional hormone therapies, there are also many natural ways to boost your levels including through supplements, some of which will be discussed later in this article.
Need the motivation to push past your comfort zone and squeeze out one more push-up or bicep curl? Sure, it helps to remember that you’ll get stronger, rock more toned muscles and rev your metabolism, thanks to all that added muscle mass. But if that wasn’t enough, now comes news that all that pump-itude (yes, that’s an SNL reference) has psychological benefits, too.
It can be hard to know where to start when beginning strength training. There are countless exercises you can do, some of which work some muscles, but not others. There are safety concerns to beware of, a wide variety of sometimes confusing equipment to help you in your efforts, and so on. With some familiarity of the basics of getting started with strength training, actually doing so can become far less daunting, and you can begin to craft a routine that is targeted toward helping you achieve your personal goals.
Caffeine is the naturally occurring alkaloid and stimulant in coffee, tea, cocoa, guarana, cola and other plant product beverages. A strong cup of brewed coffee will give you about 100 milligrams of caffeine, instant coffee around 80 milligrams, often less, and tea down around the 40 milligrams. It varies from product to product and how you prepare the drink.
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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