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.


Supplementation of a loading phase of creatine has been noted to augment the increase in RBC levels of superoxide dismutase (SOD) from exercise, when measured immediately after, by 8.1%, but control groups increased to match within an hour.[299] Glutathione (normally decreases with exercise) and catalase (increases) were both unaffected,[299] and elsewhere in vitro red blood cells incubated with 3mM of creatine (within the supplemental range) is able to improve filterability (a measure of cell rheology, or fluid structure of the cell[300]) when RBC creatine was increased by 12.3% to reach 554µM.[301] This was thought to be due to reduced oxidative stress (assessed via MDA) in the red blood cells, which in the presence of 1-5mM creatine was progressively reduced by 20-41%.[301]
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.
Because the distribution of muscle strength is unique to each there is no short answer to this question. A personal trainer simply cannot tell all his/her customers to perform a bench press using 100 pounds because it will be too difficult for some and too easy for others. Rather the idea here is to use the right amount of weight that will make you successful in accomplishing the objective set previously (muscle power, strength or endurance).
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Great Paleo beef protein, why? Because it doesn't have any preservatives, fillers, Dairy, soy, yeast, corn, or any other additives. No artificial colorings/flavorings. That makes this product not just paleo, but also autoimmune paleo friendly, hard to find. That basically means anti alergic, you dont get the same digestive issues many people get with whey. I think beef protein is underrated, I just finished a batch and went back to my whey. The whey gives me bloating/gas that this product doesnt. Also if you don't like how the amino acid profile stacks up agains Whey protein powder you can add some BCAA to powder, at least thats what I do. In a 30 gram saving you get 28 grams of protein (zero fat and zero carb), not bad!
Getting comfortable with a steady running routine is definitely something to be proud of, but when you're on that cardio grind day-in and day-out, you might be ready to change things up and take on a new challenge. Time to throw some strength training into the mix. It can be a little intimidating at first if you don't know where the hell to start, but understanding the basics can help you feel confident in your refreshed fitness routine.
Carducci, C., Birarelli, M., Leuzzi, V., Carducci, C., Battini, R., Cioni, G., and Antonozzi, I. Guanidinoacetate and creatine plus creatinine assessment in physiologic fluids: an effective diagnostic tool for the biochemical diagnosis of arginine:glycine amidinotransferase and guanidinoacetate methyltransferase deficiencies. Clin Chem 2002;48(10):1772-1778. View abstract.

A: Start with the calculations above but don’t be afraid to adjust up or down. Your metabolism and physiology will adapt to more food by trying to maintain homeostasis and regulate your bodyweight. Some may have to increase more than others but the number on the scale doesn’t lie. If it’s not going up, then you probably need to increase your calories.
Previous investigations have shown that a single dose of CM (8 grams) increased the number of repetitions performed during an upper-body resistance training protocol and reduced soreness at 24 and 48 hours post-exercise (compared to a placebo).7 Recently, researchers from Mississippi State University found that a single dose of CM (8 grams) significantly increased the number of lower-body repetitions compared to a placebo group.[8]
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]
Gains will differ from one individual to another depending on body size and level of experience in the gym. To make sure you'’re gaining muscle, not fat, don'’t just consider your scale weight. Instead, rely on what you see in the mirror and use a tape measure twice a month to keep track of your waist and hips (you don't want to gain there)— as well as your biceps, chest and quads. Also, don'’t think that you have to gain a set amount of weight each and every week. "Your mass gain doesn'’t have to be uniform,"” Aceto explains. That means you can gain 1/2 pound one week and 1 1/2 the next, perhaps none the third week and still remain on course. "“Expecting uniform gains ignores the intricate makeup of the body and the way it gains mass -— or loses fat - which is by no means in linear fashion," adds Aceto.

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]
We’re so confident that you’re going to love our supplements that we offer a 30-day guarantee. If you have any questions about any of our products, please don’t hesitate to call our friendly experts at (512) 394-7995, or feel free to email us at [email protected] The right supplements can make a tremendous difference in your workouts, so don’t wait to get started. Shop the best bodybuilding supplements at Bare Performance Nutrition now.

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]


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.
Creatine ethyl ester is more a pronutrient for creatinine rather than creatine,[74] and was originally created in an attempt to bypass the creatine transporter. It is currently being studied for its potential as a treatment for situations in which there is a lack of creatine transporters (alongside cyclocreatine as another possible example).[77] Its efficacy may rely on intravenous administration, however.

Teresa Giudice, who's best known as a personality on Bravo's Real Housewives of New Jersey, competed in her first bodybuilding contest Saturday. — Carly Mallenbaum, USA TODAY, "'Real Housewives' star Teresa Giudice shows off new muscles at bodybuilding competition," 10 June 2018 His first wife, Sitora Yusufiy, suggested in an interview with Time magazine, with little evidence other than his penchant for bodybuilding and mirror-gazing, that Omar Mateen could have been gay. — Tim Fitzsimons /, NBC News, "What really happened that night at Pulse," 12 June 2018 The physique competition will be held at McGlohon Theater and includes the following categories: bodybuilding, fitness, men’s physique, figure, bikini, classic physique and women’s physique. — Courtney Devores, charlotteobserver, "Your 5-minute guide to the best things to do in Charlotte | June 22-28," 21 June 2018 Fans who have been following Giudice closely on social media have watched the reality star workout in videos, but Giudice hasn't posted publicly about her first bodybuilding competition. — Carly Mallenbaum, USA TODAY, "'Real Housewives' star Teresa Giudice shows off new muscles at bodybuilding competition," 10 June 2018 Carolyn Marvin, who served as the graduate adviser for both Prosper and Nirenberg, pointed to his thesis, an autoethnography about the subculture of bodybuilding. — Josh Baugh, San Antonio Express-News, "Nirenberg knew immediately that he’d eventually marry Erika Prosper," 17 Mar. 2018 The bodybuilding competition is one of two hosted produced each year in Louisville by Kentucky Muscle promoter Brent L. Jones. — Matt Stone, The Courier-Journal, "Bodybuilders, fitness athletes go flex at 2018 KDF Derby Championships," 29 Apr. 2018 Father John Brown is basically a bodybuilding legend, having won two Mr. Universe titles and three Mr. World crowns. — Jr Radcliffe, Milwaukee Journal Sentinel, "Facts you may have missed about each Packers draft choice in 2018," 4 May 2018 The affable Louisville man helped bring back the bodybuilding show culture in 2011 with 90 competitors. — Matt Stone, The Courier-Journal, "Bodybuilders, fitness athletes go flex at 2018 KDF Derby Championships," 29 Apr. 2018
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.
^ Jump up to: a b c d Brosnan JT, da Silva RP, Brosnan ME (May 2011). "The metabolic burden of creatine synthesis". Amino Acids. 40 (5): 1325–31. doi:10.1007/s00726-011-0853-y. PMID 21387089. Creatinine loss averages approximately 2 g (14.6 mmol) for 70 kg males in the 20- to 39-year age group. ... Table 1 Comparison of rates of creatine synthesis in young adults with dietary intakes of the three precursor amino acids and with the whole body transmethylation flux
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.
After all, if you’re doing more reps in a set, the weight would obviously be lighter and the intensity level lower. If you’re doing fewer reps in a set, the weight is obviously heavier and the intensity is higher. In addition, how close you come to reaching failure – aka the point in a set when you are unable to complete a rep – also plays a role here.
Kilduff, L. P., Georgiades, E., James, N., Minnion, R. H., Mitchell, M., Kingsmore, D., Hadjicharlambous, M., and Pitsiladis, Y. P. The effects of creatine supplementation on cardiovascular, metabolic, and thermoregulatory responses during exercise in the heat in endurance-trained humans. Int J Sport Nutr Exerc Metab 2004;14(4):443-460. View abstract.

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.
Arginine mainly benefits the body in two ways. The first of these is by producing nitric oxide. When arginine enters the body, some of it gets converted into nitric oxide. Nitric oxide is important for regulating blood pressure, as it can enlarge the blood vessels. Larger blood vessels allow the body to increase blood flow throughout the body, bringing extra nutrients and oxygen to the muscles during exercise.
Older women with knee osteoarthritis given supplemental creatine at 20g for five days followed by 5g for the rest of the twelve week trial experienced improvements in stiffness (52% reduction), pain (45%), and physical function (41%) as assessed by WOMAC, despite no improvements in physical power output relative to placebo.[425] This study paired supplementation and placebo with a mild exercise regimen.[425]
Multivitamin supplements may help you reach the recommended daily intakes for vitamins and minerals if you have a less than ideal diet, travel impairs your diet, or strenuous exercise increases requirements. I consider a multivitamin good insurance in these circumstances against possible deficiencies. Choose a reputable brand. You should choose a good all-around supplement with a balanced formula.
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.
More recent studies on the regulation of CrT creatine transport activity have identified the protein kinase (Janus-Activating Kinase 2) JAK2, which suppresses the rate of creatine uptake via CrT without affecting creatine binding.[181] JAK2 is a regulatory protein involved in stabilizing the cellular membrane and controlling water concentrations in response to osmotic stress.[182][183] Similar to c-Src (a positive creatine transport regulator), Jak2 can also be activated by growth hormone signaling.[169][184] The growth hormone receptor seems to activate these two factors independently, as gh-mediated activation of c-Src does not require JAK2.[168] Given that c-Src is a positive regulator of CrT, JAK2 is a negative regulator, and the fact that downstream signals from both are induced by growth hormone, it is tempting to speculate that JAK2 activation downstream of the gh receptor may function as a homeostatic response to limit c-src induced creatine uptake. This has not been studied, however, and the effects of gh-induced JAK2 signaling on CrT activity have not been examined.
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 4 to 6 reps for strength and hypertrophy, 8 to 12 reps for muscular strength and 10 to 15 reps for muscular endurance. They also recommend at least one set of each exercise to fatigue although you'll find that most people perform about 2 to 3 sets of each exercise. In general:
Healthy sources of fat include: cold water oily fish (such as salmon, mackerel, and sardines), extra-virgin olive oil, peanuts (unsalted), avocado, pecans, almonds, hazelnuts, walnuts or flaxseed. Nuts (any sort, just make sure they are unsalted) are a great food to snack on if you're having trouble gaining weight, as they are not only high in calories, but they contain monounsaturated fats, a good source of protein, fibre and contain a number of essential minerals that are needed for health. For those not consuming any oily fish, you may want to consider taking a fish oil supplement, such as cod liver oil or flaxseeds.
Creatine is a natural source of energy for muscle contraction. The body produces creatine in the liver, kidneys, and pancreas. People can also get creatine by eating meat or fish. (Vegetarians may have lower amounts of creatine in their bodies.) Most of the creatine in the body is stored in skeletal muscle and used during physical activity. The rest is used in the heart, brain, and other tissues.
Universal Creatine Powder is 100% pure creatine monohydrate. Universal Nutrition supplies us with a pure, quick to absorb blend in the creatine supplement world today. Use Universal Creatine and see how you can increase the size of your muscles and improve in strength as well as endurance during your workouts. Don't let fatigue stop you from becoming who you want to be. Keep Reading »

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.
In a study on Alpha-Lipoic Acid, 1,000mg of ALA paired with 100g sucrose and 20g creatine monohydrate was more effective in increasing muscular creatine levels relative to creatine alone and creatine combined with sucrose.[600] This apparent augmentation of creatine uptake into muscle cells was used alongside a loading period. Another study investigating a nutrient mixture (150g glucose, 20g creatine, 2g/kg bodyweight glycerol) on heat tolerance in trained athletes found that replacing one third (50g) of the glucose with 1g ALA resulted in no significant differences between groups (in regard to heat tolerance and cardiovascular performance) despite the reduction of 50g carbohydrate.[601]
Most weightlifters, athletes and bodybuilders know about creatine. They know it’s an important substance to take to give you an important edge in your workouts. Kaged Muscle made two different creatine products to give you the purest edge possible. They’re known as Kaged Muscle C-HCL Powder. There is a powder version and a capsule version. Keep Reading »

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.
The process of phagocytosis (a macrophage consuming a pathogen) in macrophages appears to be associated with an acute reduction in creatine phosphate stores (45%)[436] and an increase in creatine kinase activity,[290] although prolonged stimulation is met with an increase in creatine phosphate (20%).[290] The creatine kinase activity does not appear to be altered based on creatine availability,[290] but since ATP seems to be preserved in these instances,[436][290] the increase in phosphocreatine may be explained by an overall creatine pool paralleling that found in medium.[290]
There is some research that suggests that creatine can help people with type 2 diabetes by improving insulin sensitivity, glucose uptake into the cells, and glycemic control. This has led many people with T2 to start supplementing their diets with pure creatine to try and reap the benefits. At this time there has been no conclusive research done into the effectiveness of creatine for type 1 diabetics.
Zinc is important to produce the male hormone testosterone and in building the immune system. Magnesium is an essential component of the nervous system and for maintaining heart health. Both have a range of important biochemical function. Zinc and magnesium are often marketed to bodybuilders in combination in a supplement called ZMA. Zinc is in whole grains, seeds, nuts and particularly meat and oysters. After years of research, no evidence exists to show that either mineral offers bodybuilding or athletic performance enhancement in excess of the recommended dietary requirements.
Focus on form. Good form means you can reap all of the benefits of your workout and avoid injuries at the same time. To maintain proper form, pay attention to your posture (stand tall with chest lifted and abs held tight), move slowly (this ensures you're relying on muscles, not momentum, to do the lifting), and remember to breathe. Many people hold their breath while exerting, but exhaling during the hardest part of the exercise helps fuel the movement.
The first thing you need is a weight training program that signals the muscle building process to begin. Research has shown that a well designed program will generate this “signal” via a combination of progressive tension overload (as in, getting stronger over time), metabolic stress (as in, fatiguing the muscle and getting “the pump”), and muscular damage (as in, actual damage to the muscle tissue itself).
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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.
Creatine is not an essential nutrient[19] as it is naturally produced in the human body from the amino acids glycine and arginine, with an additional requirement for methionine to catalyze the transformation of guanidinoacetate to creatine. In the first step of the biosynthesis these two amino acids are combined by the enzyme arginine:glycine amidinotransferase (AGAT, EC:2.1.4.1) to form guanidinoacetate, which is then methylated by guanidinoacetate N-methyltransferase (GAMT, EC:2.1.1.2), using S-adenosyl methionine as the methyl donor. Creatine itself can be phosphorylated by creatine kinase to form phosphocreatine, which is used as an energy buffer in skeletal muscles and the brain.
Liquid creatine has been shown to be less effective than creatine monohydrate.[69] This reduced effect is due to the passive breakdown of creatine over a period of days into creatinine, which occurs when it is suspended in solution.[70] This breakdown is not an issue for at-home use when creatine is added to shakes, but it is a concern from a manufacturing perspective in regard to shelf-life before use.
This is why I never understand why girls who don’t want to “get bulky” are told by trainers to do 3 sets of 10-12 (or 5 sets of 1,000 reps of bicep curls with a 1 lb pink dumbbell). While it’s difficult for women to gain any sort of size lifting in ANY rep range, if we were trying to gain muscle size, that’s EXACTLY what we would want to do (as it would be causing sarcoplasmic hypertrophy).
Creatine has been shown to influence androgen levels. Three weeks of creatine supplementation has been shown to increase dihydrotestosterone (DHT) levels, as well as the DHT:testosterone ratio with no effects on testosterone levels.[430] In contrast, creatine supplementation has been shown to increase testosterone levels when taken alongside a 10-week resistance training program.[431] A study in male amateur swimmers also noted that a creatine loading phase (20g daily for six days) was able to increase testosterone levels by around 15% relative to baseline.[397] 
D-aspartic acid can also help to reduce cortisol levels. Cortisol is known as the “stress” hormone because its production increases during stressful situations. High cortisol levels can have many negative side effects, such as weight gain, muscle tissue breakdown, or increased blood sugar. Taking a supplement that includes cortisol can reduce stress and prevent excess fat storage or muscle loss.
Creatine is a powerful supplement for strength and muscle gain. It always recommended utilize creatine before the workout. It gives you the strength and power of more repetition. With creatine, you can also use SR-9009. SR-9009 has the capabilities of lowering obesity and reversing metabolic syndrome. SR-9009 allows to perform more cardio training, weight loss, improve cholesterol levels, and gain lean muscle mass. Hope this information will help someone.
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.
The 100% Grass-Fed Whey Protein Isolate comes in the form of powder and can be mixed with any liquid. While the protein powder can be mixed well with water, try mixing it with milk for added calories and protein. You can even add this to smoothies and baked goods to increase the protein profile. Recommended protein intake for adults is 0.8 grams per kilogram. Some athletes may need as much as 1.2-2 grams protein per kilogram. For your specific needs, always consult a registered dietitian.
While training intensity can be accomplished trough a targeted training program and an ability to adequately stimulate our muscles is something the motivated and determined bodybuilder often has no problem doing, muscle recovery is another issue. It is especially important at a time of the year when social demands and incorrect eating combine to stifle our progress.
Despite all the awesomeness of hypertrophy, athletes may be more interested in effects on power. Power is the ability to generate high amounts of force in relatively short periods of time — more power means you can pull more weight in low-rep sets — and independent of the hypertrophy, just five to ten grams of creatine per day appears to improve power output by 12 to 26 percent.
^ Mangano, Kelsey M.; Sahni, Shivani; Kiel, Douglas P.; Tucker, Katherine L.; Dufour, Alyssa B.; Hannan, Marian T. (February 8, 2017). "Dietary protein is associated with musculoskeletal health independently of dietary pattern: the Framingham Third Generation Study". The American Journal of Clinical Nutrition. 105 (3): 714–722. doi:10.3945/ajcn.116.136762. PMC 5320406. PMID 28179224 – via ajcn.nutrition.org.
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.
I was building up, bulking, going after the mass, which to me meant 230 pounds of sheer body weight. At that time, I didn’t care about my waist or anything else that would give me a symmetrical look. I just wanted to build a gigantic 250-pound body by handling a lot of weight and blasting my muscles. My mind was into looking huge, into being awesome and powerful. I saw it working. My muscles began bursting out all over. And I knew I was on my way.”
In regard to practical interventions, concurrent glycogen loading has been noted to increase creatine stores by 37-46% regardless of whether the tissue was exercised prior to loading phase.[176] It is important to note, however, that creatine levels in response to the creatine loading protocol were compared in one glycogen-depleted leg to the contralateral control leg, which was not exercised.[176] This does not rule out a possible systemic exercise-driven increase in creatine uptake, and the increase in creatine noted above[176] was larger than typically seen with a loading protocol (usually in the 20-25% range). Consistent with an exercise-effect, others have reported that exercise itself increases creatine uptake into muscle, reporting 68% greater creatine uptake in an exercised limb, relative to 14% without exercise.[153]
Healthy sources of fat include: cold water oily fish (such as salmon, mackerel, and sardines), extra-virgin olive oil, peanuts (unsalted), avocado, pecans, almonds, hazelnuts, walnuts or flaxseed. Nuts (any sort, just make sure they are unsalted) are a great food to snack on if you're having trouble gaining weight, as they are not only high in calories, but they contain monounsaturated fats, a good source of protein, fibre and contain a number of essential minerals that are needed for health. For those not consuming any oily fish, you may want to consider taking a fish oil supplement, such as cod liver oil or flaxseeds.
One case study exists of a man with focal segmental glomerulosclerosis who experienced an accelerated rate of GFR decline during supplementation (5g thrice daily for loading, then a 2g maintenance for seven weeks) which was partially reversed upon supplement cessation. This was deemed strong circumstantial evidence, and the brand of supplement was not named.[616] Elsewhere, interstitial nephritis associated with creatine supplementation has been reported in a man, although symptoms arose four weeks after supplementation started with no evidence to support correlation.[617] Some studies involving athletes and various dietary supplements have attempted to draw a correlation with creatine and cases of rhabdomyolysis.[618][619][620][621] Finally, one study in a diabetic person ingesting both metformin and creatine resulting in metabolic acidosis has attempted to place causation on creatine, but it did not establish causation or circumstantial evidence.[622]
JAK2 (Janus-Activating Kinase 2) is a novel protein that has been shown to suppress the activity of the creatine transporter CrT in vitro. The effects of JAK2 on CrT are not well-understood in vivo, however. Given that growth hormone activates both c-src (increases CrT activity) and JAK2- which has been found to decrease CrT activity, it is plausible that JAK2 may function as a negative-feedback regulator of creatine uptake. Future research is needed to better understand the role of JAK2 on CrT activity in vivo.
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]

These effects were noted before in a preliminary study of depressed adolescents (with no placebo group) showing a 55% reduction in depressive symptoms at 4g daily when brain phosphocreatine levels increased.[231] Other prelimnary human studies suggest creatine might lessen unipolar depression[256] and one study on Post-Traumatic Stress Disorder (PTSD) noted improved mood as assessed by the Hamilton Depression Rating Scale.[232]
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