ONLINE DRIVERS MEDIA

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.

Protein before workouts "accelerates protein catabolism"? That sounds worse than it actually is (photo BSN).

Most of you will probably consume a protein shake after their workout. Probably whey, if youve read all SuppVersity articles, maybe 25g whey + 10g casein (learn why), or something like that. But what do you do before your workouts? Do you consume a protein shake 60-90 minutes before your workout? If so, you will be shocked about the conclusion of a recent study from the Tokyo University of Agriculture which says: "[...]  pre-exercise protein supplementation taken in excess may accelerate protein catabolism" (Hasegawa. 2014).

But is it actually possible that consuming more protein (albeit at the wrong time) will have a negative impact on your gains?
Before we can answer this important question it is necessary to take a look at the actual design of the randomized cross-over study.

Figure 1: Graphical overview of the experimental protocol (Hasegawa. 2014)

The participants, six healthy male university students [21.2 (±0.3) years, 173.6 (±2.8) cm, and 62.7 (±2.8)kg] with no allergies to egg white or soy, the two protein sources the effects of which the researchers initially wanted to compare, underwent three 8-day testing periods with an exercise at the end (the 8-day intervals were separated by at least seven days).

"Each  testing period began on Day-1 and ended the meat-free diet  consisting of grains, beans, and milk, and 24- hour urine sample collection on Day-8 (Figure 1). Participants were allocated into  one of three groups; egg white protein (E), soy protein (S), and mineral water control (C) group with no additive, and all were carried out this study protocol three times, and asked not to change their lifestyle behaviors." (Hasegawa. 2014). 

The result of this study should remind you of the "Protein-Wheysting" Article | more is not always better!

On Day-5, the day of the workout, the  participants arrived at the  laboratory at 8:00 AM, and had a breakfast consisting of a rice ball (energy, 355 kcal; protein, 6.7 g; carbohydrate, 78.1 g). At 9:30 AM, after the baseline blood sample collection and perceived muscle soreness (MS) measurements, the subjects received one of the three test beverages which contained

• 20 g of egg protein,
• 20g of soy protein, or
• an isoenergetic placebo without protein

that had been dissolved in 200ml of mineral water. 90 minutes later, at 11:00 AM, the previously untrained participants started a resistance training protocol that involved seated rows, flys, leg extensions, and leg presses.

The exercises were performed for three sets of 10 repetitions at ~80% of a predetermined 1-RM with one min rest between sets and two minutes between each exercise.

Figure 2: no significant difference in perceived fatique, but a significant reduction in peak muscle soreness in the soy (grey blocks) vs. the control (white triangles) group (Hasegawa. 2014).

As you can see in Figure 2, the initially mentioned negative effects of the protein supplement were not the only significant inter-trial differences the scientists observed; and whats more, the significantly decreased muscle soreness in response to both protein powders (the peak levels differed statistically significantly only for control vs. soy) stands in stark contrast the mainstream interpretation of protein breakdown (which is "protein breakdown = muscle loss").

How is that possible? Increased protein breakdown and reduced muscle soreness?

So, here we are with an obvious contradiction between the reduced muscle soreness (Figure 2) and the scientists claim that "pre-exercise protein supplementation taken in excess may accelerate protein catabolism" (Hasegawa. 2014)... you already guessed it: The contradiction depends on the false assumption that "protein catabolism" means "catabolism of muscle protein", which is not generally the case and in this specific case certainly wrong.

Figure 3: Urinary nitrogen excretion measured for 72h after the workout (Hasegawa. 2014)

The process we are talking about here is thus most likely not an increase in "mucle catabolism" but rather about the absence of a reduction in protein wasting, i.e a "protein sparing" mechanism that wont be triggered if there is plenty of protein around during the workout.
References:

• Baty, Jacob J., et al. "The effect of a carbohydrate and protein supplement on resistance exercise performance, hormonal response, and muscle damage." The Journal of Strength & Conditioning Research 21.2 (2007): 321-329.
• Hasegawa, Yuko, et al. "Effect of Egg White Protein Supplementation Prior to Acute Resistance Training on Muscle Damage Indices in Untrained Japanese Men." Monten. J. Sports Sci. Med. 3 (2014) 2: 5–12.
• Rasmussen, Blake B., et al. "An oral essential amino acid-carbohydrate supplement enhances muscle protein anabolism after resistance exercise." Journal of Applied Physiology 88.2 (2000): 386-392.
• Wycherley, Thomas Philip, et al. "Timing of protein ingestion relative to resistance exercise training does not influence body composition, energy expenditure, glycaemic control or cardiometabolic risk factors in a hypocaloric, high protein diet in patients with type 2 diabetes." Diabetes, Obesity and Metabolism 12.12 (2010): 1097-1105.