Neurological and cognitive function has also been shown to be improved by creatine supplementation [47,48]. Rawson and Venezia [49] review the effects of creatine supplementation on cognitive function highlighting that higher brain creatine has been associated with improved neuropsychological performance. Creatine supplementation protocols have been shown to increase brain creatine and phosphocreatine contents. Cognitive processing hindered due to sleep deprivation and natural impairment due to aging can be improved by creatine supplementation. This review also highlights other possible benefits of creatine ingestion to older adults, such as improvements in: fatigue resistance, strength, muscle mass, bone mineral density, and performance of activities of daily living. Some of these benefits occur without concurrent exercise. The authors inform that discrepancies between studies do exist and are hard to explain but may be possibly due to differences in diet, race and/or supplementation protocols. However, the ideal dose of creatine to maximize brain uptake is not known. Patients have been supplemented with 40 g while in healthy adults positive results have been reported with around 20 g per day [49].

Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5α-reductase. DHT binds to the same androgen receptor even more strongly than testosterone, so that its androgenic potency is about 5 times that of T.[118] The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects.
“This study establishes testosterone levels at which various physiological functions start to become impaired, which may help provide a rationale for determining which men should be treated with testosterone supplements,” Finkelstein says. “But the biggest surprise was that some of the symptoms routinely attributed to testosterone deficiency are actually partially or almost exclusively caused by the decline in estrogens that is an inseparable result of lower testosterone levels.”
The effect excess testosterone has on the body depends on both age and sex. It is unlikely that adult men will develop a disorder in which they produce too much testosterone and it is often difficult to spot that an adult male has too much testosterone. More obviously, young children with too much testosterone may enter a false growth spurt and show signs of early puberty and young girls may experience abnormal changes to their genitalia. In both males and females, too much testosterone can lead to precocious puberty and result in infertility. 

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]
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.
In addition to adequate protein, you need more calories (your protein intake contributes to your total caloric intake, so these two go hand in hand). Use the following formula to calculate the number you need to take in daily to gain one pound a week, and break down your diet using the macro guidelines listed above. (Give yourself two weeks for results to show up on the scale. If you haven't gained by then, increase your calories by 500 a day.)

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 team led by Dr. Joel Finkelstein at Massachusetts General Hospital investigated testosterone and estradiol levels in 400 healthy men, 20 to 50 years of age. To control hormone levels, the researchers first gave the participants injections of a drug that suppressed their normal testosterone and estradiol production. The men were randomly assigned to 5 groups that received different amounts (from 0 to 10 grams) of a topical 1% testosterone gel daily for 16 weeks. Half of the participants were also given a drug to block testosterone from being converted to estradiol.
When creatine supplementation is combined with heavy resistance training, muscle insulin like growth factor (IGF-1) concentration has been shown to increase. Burke et al [2] examined the effects of an 8 week heavy resistance training protocol combined with a 7 day creatine loading protocol (0.25 g/d/kg lean body mass) followed by a 49 day maintenance phase (0.06 g/kg lean mass) in a group of vegetarian and non-vegetarian, novice, resistance trained men and women. Compared to placebo, creatine groups produced greater increments in IGF-1 (78% Vs 55%) and body mass (2.2 Vs 0.6 kg). Additionally, vegetarians within the supplemented group had the largest increase of lean mass compared to non vegetarian (2.4 and 1.9 kg respectively). Changes in lean mass were positively correlated to the modifications in intramuscular total creatine stores which were also correlated with the modified levels of intramuscular IGF-1. The authors suggested that the rise in muscle IGF-1 content in the creatine group could be due to the higher metabolic demand created by a more intensely performed training session. These amplifying effects could be caused by the increased total creatine store in working muscles. Even though vegetarians had a greater increase in high energy phosphate content, the IGF-1 levels were similar to the amount observed in the non vegetarian groups. These findings do not support the observed correlation pattern by which a low essential amino acid content of a typical vegetarian diet should reduce IGF-1 production [33]. According to authors opinions it is possible that the addition of creatine and subsequent increase in total creatine and phosphocreatine storage might have directly or indirectly stimulated production of muscle IGF-I and muscle protein synthesis, leading to an increased muscle hypertrophy [2].
After all, you’ve probably seen the countless workouts, diets, supplements, programs, products and people claiming that super fast muscle growth is possible. You’ve probably also seen the click-bait headlines (“How To Build 20lbs Of Muscle In Just 6 Weeks!”) and the unbelievable transformations of supposedly “natural” people (bodybuilders, celebrities, athletes, fitness gurus on social media, etc.) that clearly prove it can happen faster than this.
Researchers have long been interested in how exercise improves cognitive thinking — and whether it can ward off dementia later in life. Now, a whole slew of new studies is comparing whether strength training affects the brain differently than cardio. One Italian study of 80 older people found that those who completed a 12-week strength regimen showed improved capacity for practical skills, whereas cardio training helped bolster them on analytic tasks. Researchers are still trying to understand the “why” behind this study — but so far, we’re impressed.
With a resistance band looped around your lower thighs, plant both feet on the floor hip-width apart ensuring that your knees remain in line with your toes. Looking straight ahead, bend at both the hips and knees, ensuring that your knees remain in line with your toes. Continue bending your knees until your upper legs are parallel with the floor. Ensure that your back remains between a 45- to 90-degree angle to your hips. This is your starting position.
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] 
Many people eat two or three meals a day and the occasional protein shake (when they remember), and then wonder why they're not putting on weight. To increase muscle mass, you have to have excess energy (calories and protein) in your system - supplied by regular small meals throughout the day. Most people have no idea how many calories they need. Do you? You may find that eating until you're full is not enough, especially if you're eating the wrong sort of calories (i.e. all carbs and no protein!). Protein is the priority followed by carbs then fat, but all are important and play a part in building mass and size.
For the bench press, start with a weight that you can lift comfortably. If you are a beginner, try lifting the bar along with 5lbs or 10lbs on each side. With arms at shoulder-width apart, grab onto the bar and slowly lower the bar until it's at nipple level; push up until your arms are fully extended upwards. Do 8–10 repetitions (reps) like this for three sets (3 x 8), adding additional weight each set. Once you have a few months of practice, slowly increase weight and go down to 6–8 reps per set, aiming to reach muscle failure at the end of the third set.

Low levels of testosterone in the body cause a number of symptoms including low sex drive, hair loss, fatigue, weakness, poor erection, loss of muscle mass, decreased bone mass, and infertility. However, low T can also cause emotional symptoms including depression, irritability, anxiety, mood changes, and sleep difficulty. Studies have shown, however, that depression does not affect only men. One study found that low T in women can also lead to depression. However, this is more common in post-menopausal women or women who are approaching the age of menopause.
In the last few years, a lot of men and women have switched over to a pellet that goes under your skin. This is probably the best way to take testosterone now. The pellet is life-changing for both men and women (the dose for women is much lower than it is for men). Women, you won’t get bulky and grow a beard when you take testosterone to achieve normal levels, but you will probably lean out a little without losing your curves, and your energy and sex drive will be amazing. Female bodybuilders who experience weird scary side effects are taking anabolic steroids.
Weak, underdeveloped glutes can be a problem if you have a history of back pain and can compromise your hip mobility and set the stage for hip impingement (if you’ve ever gotten off your bike and couldn't stand up straight without some effort, you know how that feels). “Strong glutes can prevent those issues,” says McGill. But here’s the good news: You can build yours on and off the bike with a few simple moves.
No need to worry! This myth that caffeine counteracts creatine came from the simple, but wrong logic that because caffeine accelerates the nervous system and uses more water, it would counteract creatine because creatine helps your body retain water. While both of these statements are true, it does not mean they “cancel” eachother out, all that it means is that your body will be able to stay hydrated longer if you are taking creatine and caffeine opposed to just taking caffeine.
^ Jump up to: a b c d Brosnan ME, Brosnan JT (August 2016). "The role of dietary creatine". Amino Acids. 48 (8): 1785–91. doi:10.1007/s00726-016-2188-1. PMID 26874700. The daily requirement of a 70-kg male for creatine is about 2 g; up to half of this may be obtained from a typical omnivorous diet, with the remainder being synthesized in the body ... More than 90% of the body’s creatine and phosphocreatine is present in muscle (Brosnan and Brosnan 2007), with some of the remainder being found in the brain (Braissant et al. 2011). ... Creatine synthesized in liver must be secreted into the bloodstream by an unknown mechanism (Da Silva et al. 2014a)
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]
Don’t get us wrong—cardio is important for keeping your body fat down and keeping your heart health in check. (Bonus points if you run or bike, since outdoor exercise is linked to better energy and improved mental health.) But when it comes to building muscle, hitting the treadmill won't help you much. “Every component of exercise, minus cardio, can help with muscle hypertrophy,” which is the scientific term for muscle building, says Michelle Lovitt, an exercise physiologist and trainer in Los Angeles. “Cardio tends to burn calories and puts your body in a deficit, which is great for leaning out, but not building mass.”
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]

I can’t predict what sort of results you’ll see in that first year, but it can be pretty epic if you attack it right! Muscle growth might happen slower than you want, but I expect something different will happen along the way – you’ll fall in love with this idea of building STRENGTH! In fact, getting hooked on progress, and strength training is one of the best things you can do for yourself.

In addition to conjugation and the 17-ketosteroid pathway, testosterone can also be hydroxylated and oxidized in the liver by cytochrome P450 enzymes, including CYP3A4, CYP3A5, CYP2C9, CYP2C19, and CYP2D6.[159] 6β-Hydroxylation and to a lesser extent 16β-hydroxylation are the major transformations.[159] The 6β-hydroxylation of testosterone is catalyzed mainly by CYP3A4 and to a lesser extent CYP3A5 and is responsible for 75 to 80% of cytochrome P450-mediated testosterone metabolism.[159] In addition to 6β- and 16β-hydroxytestosterone, 1β-, 2α/β-, 11β-, and 15β-hydroxytestosterone are also formed as minor metabolites.[159][160] Certain cytochrome P450 enzymes such as CYP2C9 and CYP2C19 can also oxidize testosterone at the C17 position to form androstenedione.[159]
While the aforementioned study insinuated that after was better, at this time the “just take it at any time” or maybe more appropriately, “take it when it works for you” is the best way to go. Many people take supplements that include creatine, so if that’s in your pre- or post- workout drink, you should receive all the benefits. Optimal dosing still appears to be between 2 to 5 grams per day. You can “load” for the first 5 to 7 days to help saturate your cells, but beyond that there’s no benefit to taking large amounts. So save your money and take the smaller dose; it’ll still offer maximum results.
In general, muscle content of creatine tends to be elevated to 15-20% above baseline (more than 20mM increase) in response to oral supplementation. People who get a sufficiently high influx of creatine are known as responders.[150][151][152][153] A phenomena known as “creatine nonresponse” occurs when people have less than a 10mM influx of creatine into muscle after prolonged supplementation.[154] Quasi-responders (10-20mM increase) also exist.[154] Nonresponse is thought to explain instances where people do not benefit from creatine supplementation in trials, since some trials that find no significant effect do find one when only investigating people with high creatine responsiveness.[155] There are clear differences between those who respond and those who do not, in regard to physical performance.[156] People who are creatine responsive tend to be younger, have higher muscle mass and type II muscle fiber content, but this has no correlation with dietary protein intake.[154][157]
Our bodies store creatine in our muscles so that we have quick access to it for fast, high-intensity movements, like sprinting or powerlifting, explains Autumn Bates, a certified clinical nutritionist and sports nutritionist in private practice in Manhattan Beach, California. “It's a nonessential amino acid, meaning your body creates it and you don't need to primarily get it from food.”
^ 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.
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