Mercimek-Mahmutoglu, S., Stoeckler-Ipsiroglu, S., Adami, A., Appleton, R., Araujo, H. C., Duran, M., Ensenauer, R., Fernandez-Alvarez, E., Garcia, P., Grolik, C., Item, C. B., Leuzzi, V., Marquardt, I., Muhl, A., Saelke-Kellermann, R. A., Salomons, G. S., Schulze, A., Surtees, R., van der Knaap, M. S., Vasconcelos, R., Verhoeven, N. M., Vilarinho, L., Wilichowski, E., and Jakobs, C. GAMT deficiency: features, treatment, and outcome in an inborn error of creatine synthesis. Neurology 8-8-2006;67(3):480-484. View abstract.
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.
Macrophages are known to express creatine kinase and take creatine up from a medium through a sodium dependent mechanism (likely the creatine transporter) in a saturable manner, with a second component that requires there to be no concentration gradient to work against (likely passive diffusion) but this effect tends to only account for up to 10% of total uptake in the physiological range (20-60µM). Supraphysiological range was not tested.
Creatine is mostly synthesized in the liver via AGAT and GAMT (the other locations are neurons, the pancreas, and kidneys) despite it not being stored in high levels in the liver like glycogen or adipose would be. Supplemental creatine is known to suppress AGAT by downregulating transcription, which probably occurs in humans (since the products of AGAT are reduced with creatine supplementation).
Sound complicated? Fortunately, there's an easy rule of thumb for increasing your training volume: For each exercise, perform three to six sets of six to 12 reps, resting for 30 to 90 seconds between each set, she says. The weight used should be enough that you can get out your last reps with proper form but wouldn't be able to perform any additional reps.
Weight training has also been shown to benefit dieters as it inhibits lean body mass loss (as opposed to fat loss) when under a caloric deficit. Weight training also strengthens bones, helping to prevent bone loss and osteoporosis. By increasing muscular strength and improving balance, weight training can also reduce falls by elderly persons. Weight training is also attracting attention for the benefits it can have on the brain, and in older adults, a 2017 meta analysis found that it was effective in improving cognitive performance.
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. Other prelimnary human studies suggest creatine might lessen unipolar depression and one study on Post-Traumatic Stress Disorder (PTSD) noted improved mood as assessed by the Hamilton Depression Rating Scale.
In standard dosages (5-10g creatine monohydrate) the bioavailability of creatine in humans is approximately 99%, although this value is subject to change with different conjugates (forms) of creatine and dosages. Coingestion of cyclocreatine (an analogue) can reduce uptake by about half and coincubation of taurine, choline, glycine, or beta-alanine had minimal attenuation of absorption, which is likely not practically relevant. The inhibition noted with cyclocreatine may be due to receptor saturation.
When lifting to complete fatigue, it takes an average of two to five minutes for your muscles to rest for the next set. When using lighter weight and more repetitions, it takes between 30 seconds and a minute for your muscles to rest. For beginners, working to fatigue isn't necessary, and starting out too strong can lead to too much post-exercise soreness.
Lung disease (Chronic obstructive pulmonary disease). Early research on the effects of creatine in people with chronic obstructive pulmonary disease (COPD) is inconsistent. Some research suggests that taking creating daily does not improve lung function. However, other research suggests that taking creatine may improve lung function or exercise capacity.
If you are underweight or have a naturally scrawny build, you may struggle to gain weight, let alone muscle mass, no matter what you do. Eating at all hours of the day and night can be exhausting and require frequent trips to the grocery store. Unless you are overweight, you likely need to create a caloric surplus in order to gain muscle. With a weight gainer powder, you can supplement a healthy diet with the additional calories you need to gain weight in muscle.
Do you know what happens when a person attempts to build muscle faster than they legitimately can? They fail, and then they wonder why it’s not working as quickly as they thought it would. From there, they’ll jump from workout to workout, diet to diet and useless supplement to useless supplement in the hopes of finally finding the missing link that will make it happen. But they’re never going to find it. They’ll just keep wasting their time, effort and money searching for something that doesn’t exist.
Though weight training can stimulate the cardiovascular system, many exercise physiologists, based on their observation of maximal oxygen uptake, argue that aerobics training is a better cardiovascular stimulus. Central catheter monitoring during resistance training reveals increased cardiac output, suggesting that strength training shows potential for cardiovascular exercise. However, a 2007 meta-analysis found that, though aerobic training is an effective therapy for heart failure patients, combined aerobic and strength training is ineffective; "the favorable antiremodeling role of aerobic exercise was not confirmed when this mode of exercise was combined with strength training".
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. 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) 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.
You should be keeping whichever program you are doing to no more than 1 hour of duration. Be sure that you are focusing on keeping the intensity high rather than making the workout drag on. Plus, there's no research that says marathon training sessions are better for muscle growth. Focus on keeping your rest periods under a minute and limit the small talk with other gym members.
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. This study paired supplementation and placebo with a mild exercise regimen.
Antioxidants in the diet protect against natural and synthetic chemical fragments called free radicals that are a part of daily living. Lifestyle challenges may increase your requirements for antioxidants. Vitamin C and E are the main antioxidants in the normal diet although many other plant nutrients contribute to this effect. Pollution, stress, smoking, strenuous exercise, and illness may increase your requirements for antioxidant protection.
When looking specifically at human studies, there has been a failure of creatine supplementation to induce or exacerbate kidney damage in people with amyotrophic lateral sclerosis (ALS). Subjects do not experience kidney damage for up to or over a year’s worth of supplementation in the 5-10g range. Postmenopausal women, people with type II diabetes, people on hemodialysis, otherwise healthy elderly, young people, and athletes do not experience kidney damage either. Moreover, numerous scientific reviews on both the long- and short-term safety of supplemental creatine have consistently found no adverse effects on kidney function in a wide range of doses. However, while doses >10 g/day have been found not to impair kidney function, there are fewer long-term trials using such high chronic daily intakes.
Synthesis primarily takes place in the kidney and liver, with creatine then being transported to the muscles via the blood. The majority of the human body's total creatine and phosphocreatine stores is located in skeletal muscle, while the remainder is distributed in the blood, brain, and other tissues. Typically, creatine is produced endogenously at an estimated rate of about 8.3 mmol or 1 gram per day in young adults. Creatine is also obtained through the diet at a rate of about 1 gram per day from an omnivorous diet. Some small studies suggest that total muscle creatine is significantly lower in vegetarians than non-vegetarians, as expected since foods of animal origin are the primary source of creatine. However, subjects happened to show the same levels after using supplements.
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.
Tribulus Terrestris: A fruit from the Mediterranean, this supplement has been used in the Indian traditional medicine of Ayurveda. In addition to helping increase testosterone, many people take it to increase libido and as a cardioprotective aid. (10) Unfortunately, despite the fact that there are claims that tribulus terrestris can increase testosterone levels, studies don’t back up these claims. There is some evidence, however, that it may improve athletic performance. If you want to choose one of the supplements for men, this should be your pick.
I know this goes against the recommendations you often see in stereotypical bodybuilding routines (i.e. the ones that involve having a single “chest day” or “arm day” or “shoulder day” once a week), but that’s just one of the many reasons why those types of routines suck for us natural, genetically-average people, and work best for steroid users with great genetics.
How much weight? Start with a pair of light dumbbell hand weights (2 to 3 pounds for women and 5 to 8 pounds for men). If you can’t do 12 repetitions (or reps are the number of times you do the exercise) the weight is too heavy. If your muscles don’t feel tired after 12 reps, it’s too light. Adjustable weights that can be strapped to wrists or ankles may be convenient if you have arthritis in your hands. You can also use home or gym weight machines, or resistance bands.
Back in the 1970s, scientists discovered that taking creatine in supplement form might enhance physical performance. In the 1990s, athletes started to catch on, and creatine became a popular sports supplement. The supplement is particularly popular among high school, college, and professional athletes, especially football and hockey players, wrestlers, and gymnasts.
After supplementation of creatine monohydrate (loading phase, followed by 19 weeks maintenance), creatine precursors are decreased by up to 50% (loading) or 30% (maintenance), which suggests a decrease in endogenous creatine synthesis during supplementation. This appears to occur through creatine’s own positive feedback and suppression of the l-arginine:glycine amidinotransferase enzyme, the rate-limiting step in creatine synthesis, as levels of intermediates before this stage are typically elevated by up to 75%.
Creatine supplementation has been noted to improve general wellbeing and health status (assessed by St George’s Respiratory questionnaire) of people with COPD over two weeks loading (17.1g daily with carbohydrates) and ten weeks of 5.7g maintenance. The studies that failed to find improvements with creatine supplementation on muscular performance also failed to find improvements in this rating scale, relative to placebo.
Without supplementation, approximately 14.6mmol (2g) of creatinine, creatine’s urinary metabolite, is lost on a daily basis in a standard 70kg male ages 20-39. The value is slightly lower in females and the elderly due to a presence of less muscle mass. This amount is considered necessary to obtain in either food or supplemental form to avoid creatine deficiency. Requirements may be increased in people with higher than normal lean mass. Creatine excretion rates on a daily basis are correlated with muscle mass, and the value of 2g a day is derived from the aforementioned male population with about 120g creatine storage capacity. Specifically, the rate of daily creatine losses is about 1.6%-1.7%, and mean losses for women are approximately 80% that of men due to less average lean mass. For weight-matched elderly men (70kg, 70-79 years of age) the rate of loss of 7.8mmol/day, or about half (53%) that of younger men.
In otherwise healthy adults subject to leg immobilization for two weeks while taking 20g creatine daily during immobilization and then 5g daily during eight weeks of rehabilitation, it was noted that the creatine group failed to reduce atrophy during the immobilization (10% reduction in cross sectional area and 22-25% reduction in force output) despite preventing a decrease in phosphocreatine, yet experienced a significantly enhanced rate of regrowth and power recovery. A similarly structured and dosed study has also noted greater expression of skeletal muscle, GLUT4 expression, and a 12% increase in muscle phosphocreatine content.
The incidence of liver damage from herbal and dietary supplements is about 16–20% of all supplement products causing injury, with the occurrence growing globally over the early 21st century. The most common liver injuries from weight loss and bodybuilding supplements involve hepatocellular damage with resulting jaundice, and the most common supplement ingredients attributed to these injuries are catechins from green tea, anabolic steroids, and the herbal extract, aegeline.
It was later noted that creatine was able to nonsignificantly augment various proinflammatory cytokines (CCL2, iNOS, ICAM-1, TGF-β, TIMP-1) and the presence of eosinophils in lung tissue, as well as to per se cause lung infiltration of these immune cells without requiring the presence of the allergen. Neutrophils and macrophages were unaffected, reflecting the past study of no influence on macrophages, but the only instance where creatine appeared to either significantly add to ovalbumin or to per se induce statistically significant increases were in IL-5 secretion and goblet cell infiltration, although VCAM-1 expression was close. While creatine per se increased nF-κB activity, it suppressed the ovalbumin-induced increase.
Eat 1.5–3 grams of carbs per pound of your body weight. As with fat, this amount can vary greatly, depending on your personal needs and preferences, so consider these numbers only a starting point. If you’re very skinny and feel that you handle carbs well (i.e. you can eat a lot of them without getting fat), go ahead and eat according to the higher end of the spectrum. The same applies if you’re desperate to gain weight—you should increase your carb intake. If you’re prone to weight gain or feel lethargic on higher carbs, you should eat fewer of them. Again, see our keto guide for more details and options.
Key point: Past a certain number of sets, the marginal increases in protein synthesis NO LONGER outweigh the cost of doing more sets. If 8 sets of chest exercises produce 95% of possible muscle protein synthesis… then it makes very little sense to do ANOTHER 10 sets (like most chest workouts) to try and inch out the final 5% of stimulation. Those extra 10 sets are simply damaging your muscle unnecessarily and impairing your ability to recover.
Safety. Excess quantities of antioxidants may produce a ‘pro-oxidant’ effect, which is the opposite of what you would take these supplements for. The Australian Institute of Sport recommends that antioxidant vitamin supplements only be taken for a period of a few weeks while the body adjusts to stressful circumstances. Excess vitamin C may promote excess iron absorption, which may not be healthy for everyone.
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.
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