ONLINE DRIVERS MEDIA

Creatine, obviously monohydrate and no expensive and often impotent spinoff (Jäger. 2011) is useful for any athlete.

The number of items on the list of health and performance benefits of creatine is about as high as the number of boring articles about "the benefits of creatine" you can find all over the Internet. And even here at the SuppVersity they have been piling up in a way that has me ignore the majority of "creatine supplementation increases strength gains in XY" studies that appear on a monthly, sometimes weekly basis. Against that background I will cut todays creatine post short and get straight to the facts, Giuseppe Potrick Stefani et al. report in their latest paper in (how else could it be) the peer-reviewed Journal of the International Society of Sports Nutrition (Stefani. 2014).
In what turns out to be another rodent study Stefani et al. investigated whether creatine supplementation exerts intra and/or extracellular antioxidant effects and if it plays a synergistic role in the adaptation of antioxidant enzymes associated with resistance training. The actual aim of the study was thus

"to evaluate the effects of monohydrate creatine supplementation associated, or not, with RT on oxidative stress and antioxidant enzymatic activity in the plasma, the heart, the liver and the gastrocnemius of rats." (Stefani. 2014)

And the results were unambiguous. As you can see in Figure 1, the anti-oxidant capacity of plasma, heart and liver of all 40 male Wistar rats which had been divided into four groups, i.e.

• sedentary (SED),
• sedentary + creatine  (SED-Cr), and
• resistance training (RT) and resistance training + creatine (RT-Cr),

increased significantly in response to the provision of creatine (0.3 g/kg/day of creatine for seven days, 0.05 g/kg for the rest of the 8-week study period).

Figure 1: Oxidative stress in heart, liver and muscle after 8 weeks of intervention.Concentrations of MDA and CAT activity. Values are mean ± SD; n = 10 for all groups (Stefani. 2014).

As you can see, both treatments, creatine-only and creatine + resistance training led to significant improvements in heart, liver and muscle antioxidant status - and that, this is important, in the absense of those direct free radical scavenging abilities that turn vitamin C, vitamin E & co into highly questionably agents with potential anti-adaptational effects (learn more).

Works w/ and w/out exercise, but with the latter creatine really excels

Compared to the sedentary animals the rats in the exercise group did yet significantly increased catalase levels (=good, because it catalyzes the decomposition of hydrogen peroxide - the bad stuff - to water and oxygen - the benign stuff) in the heart and - obviously - increased strength gains.

Figure 2: Absolute and relative 1RM strength before and after the intervention (Stefani. 2014).

What is (positively) surprising, at first, is the fact that the latter, i.e. the increases in 1-RM strength in response to creatine supplementation occurred even in the absence of resistance training.

If you look closely, you will yet realize that the relative increase in strength, a much better gauge for lasting real-world strength gains, in the sedentary rodents was ZERO. So that it is very likely that they would disappear with the increased water the rats were holding, as soon as the creatine supplementation is seized.
References:

• Jäger, Ralf, et al. "Analysis of the efficacy, safety, and regulatory status of novel forms of creatine." Amino Acids 40.5 (2011): 1369-1383.
• Stefani, Giuseppe Potrick, et al. "Effects of creatine supplementation associated with resistance training on oxidative stress in different tissues of rats." Journal of the International Society of Sports Nutrition 11.1 (2014): 11.

Creatine is a dangerous steroid? Well, the study at hand shows that it will prevent not promote hepatic lipid accumulation as you will see it with many oral steroids.

As a SuppVersity reader you either take creatine or do at least know that its the #1 proven ergogenic your money can buy! What I am pretty sure, though, is that you didnt know yet that creatine will not just make your muscles big, but also your liver clean... clean or rather free of fat.

Non-alcoholic fatty liver disease (NAFLD) has been associated with obesity and decreased insulin sensitivity. A fatty liver is considered the hepatic manifestation of the metabolic syndrome ("Liver Enzymes the #1 Marker of Insulin Resistance!?" | learn more), if creatine would effectively protect the increase in liver fat, which is the hallmark of NAFLD, it could thus eventually make the transition from the fitness community into the mainstream.
Current data suggests that 20–30% of North Americans have NAFLD, which could progress to more severe liver damage if left untreated. If taking creatine could make them stronger and healthier (remember creatine will also improve your glucose management), the amino acid of which many doctors still believe that it was a dangerous steroid could soon make it onto their prescription lists.

Current clinical treatments for fatty liver are after all limited and so the search for safe and effective therapy is important. In vivo, phosphatidylcholine (PC) synthesis is a major consumer of hepatic methyl groups accounting for approximately 40% of all transmethylation reactions, and is an important determinant of hepatic TG metabolism. Hepatocytes have the highest activity of phosphatidyl-ethanolamineN-methyltransferase (PEMT) and they synthesize a significant portion of PC via the sequential methylation of phosphatidyl-ethanolamine (PE) - a process that relies on the methyl donor betaine which happens to have similar, albeit less pronounced ergogenic effects than cretine (learn more).
De novo creatine biosynthesis occurs in the liver via the S--adenosylmethionine-dependent methylation of  guanidinoacetate (GAA) and is a major consumer of hepatic methyl groups, estimated to account for 40% of total methylation reactions in the body.

Suggested Read: "Supercharging Creatine With Baking Soda: Study Shows Increased Peak Power and Endurance - Plus: How Bicarbonate Could Help You Lose Fat & Build Muscle" | read more

Dietary creatine supplementation can reduce plasma GAA levels by 90% and therefore reduces demand on hepatic methylation. Previously, Jacobs & da Silva (2013) hypothesized that dietary creatine supplementation may spare AdoMet for PC synthesis, thus protecting the liver from TG accumulation. Dietary creatine supplementation prevented TG accumulation and the lowering of AdoMet in the liver of rats fed a high-fat diet (HFD).

Interestingly, dietary creatine did not alter hepatic PC levels or PEMT activity; therefore, the mechanism(s) through which creatine reduces fatty liver does not appear to be related to AdoMet availability.

In the study at hand, Silva et al. utilized the McArdle RH-7777 (McA) immortalized hepatoma cell line, 0 an established model for the study of hepatic lipid metabolism that does not express PEMT, to assess whether creatine might have a direct action on TG synthesis in liver cells.
What they observed were significant increases in PPAR?-activity, as they have previously reported for agents like fish oil. The increase in PPAR?-activity in turn triggered an increase in hepatic fatty acid oxidation and TG secretion and would thus help clear the triglycerides from the liver before they can harm you.

Figure 1: The reduced hepatic lipid accumulation in the cell study at hand is a consequence of (A) reduced synthesis and (B) increased secretion of triglycerides (da Silva. 2014b)

The data in Figure 1 underline that this effect is mediated by decreases in hepatic lipid synthesis (A) and an increase in lipid efflux in response to being exposed to creatine. Overall, this leads to significantly reduced cellular triglyceride levels (TG; Figure 1, left).

Reduced synthesis, increased efflux, increased oxidation

Similar effects were observed for the hepatic phospholipid (PL) content, which was likewise reduced by (a) a reduced synthesis and (b) an increase efflux of PLs. But (a) and (b) are not the only factors contributing to the healthy lipid depletion.

Figure 2: Increased triglyceride oxidation, yes, increased AMPK & ACC, no (da Silva. 2014b)

As you can see in Figure 2, the provision of extra-creatine will also increase the oxidation of fatty acids (CO2 production is a measure of fatty acid oxidation), without however having similar beneficial effects on the expression of AMPK and its fatty acid oxidating cousin ACC (see Figure 2, right) - thats in contrast to alpha-lipoic acid (learn more) and suggests that the effects are not mediated via the existing anti-oxidant effects of creatine of which youve read in "The Overlooked Non-ROS-Scavenging Antioxidant Effects of Creatine Monohydrate" (learn more)

References:

• da Silva, Robin, Karen Kelly, and Rene Jacobs. "Hepatic carbohydrate and lipid metabolism are altered in rats fed creatine-supplemented diets (LB151)." The FASEB Journal 28.1 Supplement (2014a): LB151.
• da Silva, Robin P., et al. "Creatine reduces hepatic TG accumulation in hepatocytes by stimulating fatty acid oxidation." Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids (2014b). 
• Engelhardt, Martin, et al. "Creatine supplementation in endurance sports." Medicine and Science in Sports and Exercise 30.7 (1998): 1123-1129.
• Jacobs, Rene L., Robin da Silva, and Randy Nelson. "Creatine Supplementation may prevent NAFLD by stimulating fatty acid oxidation." The FASEB Journal 27 (2013): 222-2.
• Opt Eijnde, B., et al. "Effect of oral creatine supplementation on human muscle GLUT4 protein content after immobilization." Diabetes 50.1 (2001): 18-23.