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.

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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.

Do you want to burn some extra fat during your workouts? Ilex can help. But will it also help you lose body fat?

After the nicotine article a week ago, its about time to take a look at less "toxic" fat burners. As the case may be, researchers from the Faculty of Health and Wellbeing at the Sheffield Hallam University have just published a paper about the ability of Yerba Maté (Illex Paraguariensis | YM) to augments fat oxidation and energy expenditure during exercise at various submaximal intensities (Alkhatib. 2014).

Now, as a SuppVersity Reader youre well aware that an "augmentation of fatty acid oxidation during exercise", alone, is not worth your heard earned money. The question to keep in mind, when were going through the results, is thus: Is Ilex Paraguariensis worth using, or is it just worth writing about in a science magazine?
Alright, now that weve set the scene its about time to take a look at the study design. The study followed a double-blind crossover repeated measures experimental design.

The participants were fourteen healthy adults, seven males and seven females [Mean ± SD: age = 20.8 ± 3.4 yr, height = 171.8 ± 10.0 cm, body mass = 70.4 ± 11.3 kg, body mass index (BMI; in kg/m²) = 23.8 + 0.11]. Participants were assigned randomly to each experimental condition within a period of two weeks.

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Female participants were studied in days 1 to 7 of their menstrual cycle to minimise the influence of cyclical changes in female hormones. All participants were screened prior to the start of the testing in order to determine that they are free from illness and any type of orthopaedic limitation or injury, or chronic disease.

Moreover, none of the subjects consumed ergogenic aids or tons of caffeine regularly (<200 mg/day) - that doesnt mean they never drank more coffee, but they had to abstain from more than 1.5 cups of coffee, tons of energy drinks caffeine containing soft drinks or medications.

A very reasonable request, if you want to measure significant effects from Ilex Paraguariensis which contains 1.5% (according to Alkhatib. 2014) caffeine and roughly 0.12% theobromine (according to Reginatto. 1999).

The tests & supplements

All participants reported to the Physiology Laboratory on two separate occasions following 10 hrs overnight fast, and each testing session (between 07:00am and 10:00am) was separated by at least three days within two weeks period.

During each visit participants ingested either 1000 mg (2× 500 mg capsule) YM or hydroxypropyl methylcellulose placebo empty capsules (PLC). Two capsules with similar coatings of either YM and PLC capsules were placed within an empty water cup and taken in the same way with a 100 ml of water. The YM capsules contained a standardized ground YM leaves (batch number 0422009/2012) with a natural content of approximately 1.5% caffeine (Rio Trading Company, Brighton, United Kingdom).
Immediately following the ingestion of supplement or placebo, participants rested for 60 minutes in a semi-recumbent position in quiet laboratory condition. For the estimation of FAO and CHO at rest and during exercise, breath by breath cardiorespiratory measurements included oxygen uptake ( ) 2 VO , carbon dioxide production, and respiratory exchange ratio (RER), using an online gas analyzer (Metalyzer Cortex 3B, Leipzig, Germany).

The exercise protocol & its consequences

All participants followed the same incremental exercise assessment using an electromagnetically braked cycling ergometer (Schoberer Rad Messtechnik, SRM, Ergo, Julich, Germany). The ergometer was calibrated before use and similar cycling positions were applied in both tests for each participant, which included adjusting the handlebar and saddle height and distance, crank length and toe clip positions during the first visit and re-apply the same position in the following visit.

The cycling protocol consisted of three-minute incremental stages that were initiated at and increased by 0.5 W/kg body mass. Participants cycled at 60–70 rpm throughout the whole test until volitional exhaustion defined as meeting the at least two of 2 peak VO2 termination criteria: RER value > 1.1, heart rate within 10 beats/min of age predicted maximum heart-rate, or achieving levelling-off of VO2 Peak power (P_peak). Similar verbal encouragement was provided to all participants throughout the exercise tests. All tests were followed by a sufficient cool down for at least 20 min, in which participants consumed at least 200 ml of water, and instructed to stay hydrated and consume at least 2 litres of water during the day of the test.
Interestingly, following the 60 min rest after YM ingestion, no significant difference was found for either resting blood lactate contentration (1.4 ± 0.32 vs. 1.5 ± 0.30 mmol/l) or resting respiratory exchange ratio (0.82 ± 0.08 vs. 0.81 ± 0.05) for PLC vs. YM respectively.

In other words: After the workout there were no measurable difference between the active and placebo treatment. The latter cannot be said of the RER during workouts, though.

Figure 1: Significant decreased RER and higher fatty oxidation rates - two sides of the same fat burning coin and evidence that the ingestion of the YM supplement lead to significant increases in fatty oxidation (Alkhatib. 2014)

As you can see in Figure 1 the effects of the Ilex supplements were significant - statistical significant, but also practically relevant? Probably not. The increase in fatty oxidation was after all paid for with an increase in glucose oxidation (see Figure 2).

Figure 2: The glucose usage during workouts decreases, obviously this leads to greater increases in lactate levels, whether its pro-weight loss is questionable, though. If anything it could increase the time to fatigue (Alkhatib. 2014)

The net energy expenditure, the one thing that really counts, was thus identical. For someone who has to get rid of tons of fat in his blood. The increase in RER may be relevant. For someone who is fit and well-trained, its not really important if he or she burns fat or glucose during the workout - why else would HIIT work so well for losing fat - specifically in lean athletic individuals? Well, the answer is easy: It burns glucose and will thus increase GLUT-4 expression insulin sensitivity and, in the end, also fatty oxidation - to replete the depleted energy stores.
References:

• Godfrey, R. J., et al. "A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance: Part 45." British journal of sports medicine 47.10 (2013): 659-660.
• Pang, Jisook, Youngshim Choi, and Taesun Park. "Ilex paraguariensis extract ameliorates obesity induced by high-fat diet: Potential role of AMPK in the visceral adipose tissue." Archives of biochemistry and biophysics 476.2 (2008): 178-185.
• Reginatto, Flavio Henrique, et al. "Methylxanthines accumulation in Ilex species-caffeine and theobromine in erva-mate (Ilex paraguariensis) and other Ilex species." Journal of the Brazilian Chemical Society 10.6 (1999): 443-446.