How it is Tops for Increasing Muscle Mass
Creatine continues to make news again, with several studies shedding new light on exciting new mechanisms that show how creatine enhances muscle mass and increases muscle recuperation.
Is Creatine an Antioxidant?
Researchers from Italy published new research on the mechanisms whereby creatine can enhance muscle recuperation and muscle mass, especially in the aging population. Creatine (Cr) was previously shown to enhance muscle growth by directly increasing muscle IGF-1 levels and enhancing satellite cell activation. Among the known growth factors, IGF-1 is known to stimulate satellite cell activity as well as protein synthesis, as well as increase muscle hypertrophy. In fact, IGF-1 is such a potent stimulator of muscle hypertrophy that infusion of local IGF-1 directly to skeletal muscles has been demonstrated to increase muscle mass.1
It was previously reported that when muscle cells were cultured in test tubes, the addition of Cr resulted in increased expression of muscle IGF-1 mRNA.2 This means that creatine enhances muscle growth even when you are just lying around, but exercise is going to enhance the effect. You may be saying, “I ain't no damn test tube— so give me the human studies!”
Human studies have shown that Cr supplementation also increases mRNA IGF-1 activity. In a double-blind crossover design, muscle biopsies were taken from the legs of resistance-trained men at rest and 3 and 24 hours post-exercise, who took Cr or protein/carbohydrate drinks for five days. After Cr supplementation, resting muscle expressed more mRNA for IGF-1 (+30 percent). IGF-1 was raised (+24%) three hours after exercise, and even more (+29%) 24 hours post-exercise— but this effect was not increased by Cr supplementation.
It’s interesting that in the study, Cr increased mRNA IGF-1 activity without exercise. Researchers concluded that the increase in lean body mass often reported after Cr supplementation could be mediated by signaling pathway(s) involving muscle mRNA IGF-1.3 So now that you understand that creatine increases IGF-1 levels, let’s examine a new role of creatine: protection from cellular damage.
Getting back to the new Italian study, researchers found that creatine has potent antioxidant activity on the cellular level. They demonstrated that creatine prevents what’s called ‘oxidative stress’ in skeletal muscle. Oxidative stress is the result of free radical damage, which causes massive cell damage that can result in cellular mutations, tissue breakdown and immune compromise.
What are free radicals, you ask? They are highly-unstable molecules that interact quickly and aggressively with other molecules in our bodies to create abnormal cells. They are capable of penetrating the DNA of a cell and damaging its ‘blueprint’ so that the cell will produce mutated cells that can replicate without normal controls.
Free radicals are unstable because they have unpaired electrons in their molecular structure. This causes them to react almost instantly with any substance in their vicinity. Oxidative stress is detrimental to muscle growth because it impairs the ability of newly-formed muscle fibers to grow into mature muscle fibers. An increase in oxidative stress, coupled with a cell’s inability to produce essential energy molecules such as ATP, is a hallmark of the aging cell and is found in many disease states.
Though an incredibly complex topic, the aging and ultimate fate of a cell— which is directly related to our fate as humans— depends on the ability of the cell to prevent mitochondrial damage to DNA caused by reactive oxygen species, and to prevent concomitant decline in ATP synthesis, which reduces whole-body ATP levels. It would appear that maintaining antioxidant status (i.e., glutathione) and ATP levels is an essential combination in delaying the aging process.
This newest study published in the Journal of Molecular Nutrition and Food Research found that creatine shields muscle cells from oxidative stress.4 Thus, creatine protects muscles under stressful conditions and prevents oxidative stress from damaging the mitochondria of the cell. Based on this research, creatine could be considered an anti-aging supplement.
Creatine Increases DHT-to-Testosterone Ratio
Testosterone can stimulate muscle growth by increasing protein synthesis and preventing muscle tissue breakdown. Creatine has been shown to increase muscle mass, but its effect on testosterone has been controversial. In two studies, increased growth hormone and T responses were seen immediately after exercise in subjects who supplemented with creatine, combined with branched-chain amino acids, taurine, caffeine, and glucouronolactone.5,6 The question is: which ingredient was responsible? Was it creatine or some other ingredient?
Another study found increased levels of testosterone in resting blood samples after 10 weeks of resistance training with creatine supplementation, compared to placebo, and with creatine and beta-alanine supplementation.7 Contrary to these findings, one study reported that creatine had no effect on resting testosterone levels in trained subjects, despite the loading phase of seven days.6 Another study found that creatine combined with HMB did not enhance testosterone levels.8 So does creatine raise testosterone— yes or no?
Twenty young males (aged 18 through 19) from a Rugby Institute situated near Stellenbosch University in South Africa took part in a study. Subjects were randomized into two groups for a double-blind, placebo-controlled crossover design. Subjects underwent a seven-day loading period with creatine supplementation or placebo, followed by a 14-day maintenance dose (creatine or placebo). Creatine monohydrate was given with glucose (25 grams per day of creatine and 25 grams per day of glucose) for a loading dose. Five grams per day of creatine and 25 grams per day glucose were given for a maintenance dose. The placebo group received glucose only (50 grams per day) for a loading dose and 30 grams per day for a maintenance dose.
This was the first study to report an increase in the dihydrotestosterone (DHT)-to-T ratio in response to creatine loading— a response that was also maintained during the maintenance phase for at least another two weeks in young, trained athletes. Testosterone can be converted into a more bioactive metabolite, DHT, by 5-alpha reductase. In addition, biochemical studies of androgen receptor affinity indicate that DHT is four times more biologically potent than T.9
Creatine supplementation can be beneficial for older individuals as well as people just starting a resistance exercise program. Supplementation has been shown to improve protein synthesis, enhance cell hydration, increase growth hormone levels, and lower excess cholesterol.
In 1997, Italian researchers discovered that retaining muscle mass is the most important factor determining our ability to experience a longer, healthier life. Studies indicate that a loss of muscle mass correlates to loss of brain and nervous system function.
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