Creatine is mostly synthesized in the liver via AGAT and GAMT[28][32] (the other locations are neurons,[34] the pancreas, and kidneys[33]) 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,[30] which probably occurs in humans (since the products of AGAT are reduced with creatine supplementation).[38]
It is possible that females could benefit more than males due to a combined lower creatine kinase activity as well as having altered purine metabolism during depression,[257] but no human comparative studies have been conducted yet. One rat study noted that creatine monohydrate at 2-4% of feed had 4% creatine able to exert anti-depressive and anxiolytic effects in female rats only.[228]
A typical creatine supplementation protocol consists of a loading phase of 20 g CM/d or 0.3 g CM/kg/d split into 4 daily intakes of 5 g each, followed by a maintenance phase of 3-5 g CM/d or 0.03 g CM/kg/d for the duration of the supplementation period [5]. Other supplementation protocols are also used such as a daily single dose of around 3 – 6 g or between 0.03 to 0.1 g/kg/d [15,55] however this method takes longer (between 21 to 28 days) to produce ergogenic effects [5]. Sale et al [56] found that a moderate protocol consisting of 20 g CM taken in 1g doses (evenly ingested at 30-min intervals) for 5 days resulted in reduced urinary creatine and methylamine excretion, leading to an estimated increase in whole body retention of creatine (+13%) when compared with a typical loading supplementation protocol of 4 x 5 g/d during 5 days (evenly ingested at 3 hour intervals). This enhancement in creatine retention would lead to a significantly higher weight gain when people follow a moderate protocol ingestion of several doses of small amounts of CM evenly spread along the day.
Magnesium-chelated creatine typically exerts the same ergogenic effects as creatine monohydrate at low doses.[78] It was created because carbohydrates tend to beneficially influence creatine metabolism and magnesium is also implicated in carbohydrate metabolism and creatine metabolism.[79][80] Magnesium chelated creatine may be useful for increasing muscle strength output with a similar potency to creatine monohydrate, but without the water weight gain, as there are noted differences, but they are statistically insignificant.[80][81]
Furthermore, because creatine can help restore ATP levels, increasing energy, it can lead to reduced amounts of heart muscle stress. More energy in your life will result in less pain, stress, and boost morale in everyday life which has a significant role in improving heart health. The increased capacity to exercise is also crucial in maintaining and improving heart health.
If you stop getting the results you want after several weeks of working out, it's time to mix things up. You need to challenge or "confuse" your muscles often to keep them growing. You can do this by putting a twist on your basic moves. Do a biceps curl with a reverse grip, for example. Or find a bench for the step-up move shown here. Change up your workout at least every 4 to 6 weeks for the best results.
In humans, studies that investigate links between serotonin and creatine supplementation find that 21 trained males, given creatine via 22.8g creatine monohydrate (20g creatine equivalent) with 35g glucose, relative to a placebo of 160g glucose, was found to reduce the perception of fatigue in hot endurance training, possibly secondary to serotonergic modulation, specifically attentuating the increase of serotonin seen with exercise (normally seen to hinder exercise capacity in the heat[233]) while possibly increasing dopaminergic activity (conversely seen to benefit activity in the heat[234]).[155] 

Generally, you should consume about 20 grams of protein with some carbs shortly after a workout. During the post-workout anabolic window, you’ll also want to limit fats, which can slow the absorption of protein. While there is some recent research that suggests the window may actually extend up to several hours following exercise, there’s no harm in getting nutrients in early as long as you’re sticking to your overall caloric and macronutrient goals.

Now that you've got the training part down, it's time to stretch it out. (Can you say ahhh?) Stretching while your muscles are warm can help improve your flexibility, says Davis, not to mention it just feels phenomenal after you've pushed yourself hard. A light cool-down is also great for calming the nervous system. While dynamic stretches should be your go-to during a warm-up, the cool-down is where static stretching comes in—this means holding a stretch for 20-30 seconds. These four passive stretches will do nicely.


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Some other cytokines and hormones may increase the receptor activity. These include growth hormone (GH) which acts upon the growth hormone receptor (GHR)[166][167] to stimulate c-Src[168][169] which directly increases the activity of the CrT via phosphorylation. This is known to occur with the 55kDa version of c-Src but not the 70kDa version and requires CD59 alongside c-Src.[170]
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]

The general sentiment among nutrition experts is that creatine monohydrate is, for most people, the best bet. It’s the cheapest form and more importantly, it’s the most well-researched. Hundreds of studies have been performed on creatine monohydrate and there’s no evidence of ill effects, whereas many of the more novel forms of creatine have one or sometimes no studies supporting them.


There is a genetic condition known as gyrate atrophy of the choroid and retina, which is associated with a high level of Ornithine in the blood and a relative decrease in Arginine, which causes a relative creatine deficiency due to L-arginine being required to make creatine[478][479] and because high ornithine can suppress creatine synthesis (AGAT) in the glial cells of the retina.[475] This condition can be attenuated by either reducting ornithine in the diet[480] or by supplementing creatine, which is, in this instance, therapeutic.[481][482]
Retinol (Vitamin A) B vitamins: Thiamine (B1) Riboflavin (B2) Niacin (B3) Pantothenic acid (B5) Pyridoxine (B6) Biotin (B7) Folic acid (B9) Cyanocobalamin (B12) Ascorbic acid (Vitamin C) Ergocalciferol and Cholecalciferol (Vitamin D) Tocopherol (Vitamin E) Naphthoquinone (Vitamin K) Calcium Choline Chromium Cobalt Copper Fluorine Iodine Iron Magnesium Manganese Molybdenum Phosphorus Potassium Selenium Sodium Sulfur Zinc
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]
Entry into neural tissues in general is mediated by the secondary creatine transporter (CrT-2) known as SLC6A10,[186] which is the same transporter that is active in a male’s testicles.[145] CrT-2 belongs to the family of SLC6 transporters that act to move solutes across the membrane by coupling transport with sodium and chloride.[187][188] Genetic deletions in the 16p11.2 region, which encodes both SLC6A8[189] and SLC6A10[186] can result in severe mental retardation in humans and is one of the causes of “Creatine Deficiency Syndrome.” Creatine Deficiency Syndrome is not only caused by lack creatine transporter expression, however, as creatine synthesis is also critical for neural function.[190].[189] Retardation caused by defective creatine synthesis[31] can be reversed with creatine supplementation and dietary changes.[191]
Anti-cancer effects have been observed with the creatine analogue cyclocreatine[456][104][457] and have been replicated with creatine itself. These effects tend to be a reduction in which the rate of implanted tumors progresses.[458][459] It is suspected that these observed effects (inhibition of growth or attenuation of the rate of growth) are not due to the bioenergetic effect of creatine, secondary to creatine kinase. These anti-cancer effects do not have a known reliability, as the expression of creatine kinase varies widely based on the type of tumor.[460] However, some studies suggest an inverse relationship between tumor progression in mice and concentrations of creatine in cells, with creatine depletion coinciding with tumor development.[460]
Another study demonstrated that females receiving 4 days of high-dose creatine intake (20 g/day) followed by low-dose creatine intake (5 g/day) during 10 weeks of resistance training (3hours/week) increased muscle PCr concentrations by 6%. Also, maximal strength of the muscle groups trained increased by 20-25%, maximal intermittent exercise capacity of the arm flexors increased by 10-25% and fat-free mass increased by 60% [11].
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