Reactive Oxygen Specimen (ROS) Trigger Muscle Hypertrophy via IGF-1 Signaling

I have touched on the "usefulness" of oxidation, only yesterday. Now, a very recent study appears to confirm the notion that a controlled amount of inflammation is necessary in order to achieve metabolic and muscular adaptations.

Figure 1: Eesult of the quantitative analysis of myotube diameter after IGF-I and NAC treatment (Handayaningsih. 2011)

Scientists from Division of Diabetes and Endocrinology and Division of Cellular and Molecular Medicine at the Kobe University Graduate School of Medicine published a paper (Handayaningsih. 2011) describing an investigation into the role of Reactive Oxygen Specimen (ROS) in the IGF1-signaling pathway. In this study N-Acetyl-Cystein (NAC), commonly used by recreational athletes as an "ergogenic" aid, blunted myocyte response to IGF1 and thus inhibited muscle hypertophy (cf. Figure 1):

While treatment with H2O2 significantly enhanced IGF-I-induced phosphorylation of the IGF-I receptor (IGF-IR), IGF-IR phosphorylation was markedly attenuated when cells were treated with antioxidants. The downstream signaling pathway, Akt-mTOR-p70S6K was subsequently down-regulated. Furthermore, thephosphorylationof FoxO1by IGF-I decreased concomitantly with the restoration of the expression of its target genes, Atrogin-1 and muscle RING finger 1, which are related to muscle atrophy.

Before you now go and flush all your vitamins and antioxidants down the toilette, you should consider that this is an in-vitro study with a narrow and limited ROS stimulation and not a large scale exercise supplementation study showing that the 500-1.000 mg of NAC you take on a daily basis will completely forestall muscle growth. If anything, it should remind you that excessive "inflammation" could be the "root of all evil" (cf. Super Human Radio), but excessive antioxidant supplementation certainly ain't a solution.

Lower Protein to Carb Ratio Impairs Akt/TOR Signaling Pathway after Fasting in Rainbow Trout

"Boy, you need your carbs post workout!" This cornerstone of conventional bodybuilding wisdom is crumbling and a new study, if it had been done in humans, not in rainbow trout, would potentially refute this myth once and for all - at least, if one follows the popular (but false) assumption that it is because you are in a carb depleted or overall fasted state after a strenuous workouts.

A group of European scientists (Seiliez. 2011) investigated the effect of diets with different protein to carbohydrate ratios on the Akt/TOR Signaling Pathway after fasting for 48h. What they found contradicts conventional wisdom:

Activation of the Akt/TOR signaling pathway by refeeding was severely impaired by decreasing the proteins/carbohydrates ratio. Similarly, post-prandial regulation of several genes related to glucose (Glut4, glucose-6-phosphatase isoform 1), lipid (fatty acid synthase, ATP-citrate lyase, sterol responsive element binding protein, carnitine palmitoyltransferase 1 and 3-hydroxyacyl-CoA dehydrogenase) and amino acid metabolism (serine dehydratase and branched chain α-keto acid dehydrogenase E2 subunit) only occurred when fish were fed the high protein diet. On the other hand, diet composition had a low impact on the expression of genes related to muscle protein degradation.

So, not only did an increase in carbohydrates negatively impact muscle protein synthesis stimulated by the Akt/TOR signaling pathway, interestingly it also failed to reduce muscle protein degradation, which is the second reason people use in favor of a high carb meal after workouts (/fasting). 

For people following the research and writings of low carb proponents such as Mauro di Pasquale these results may not be surprising. However, before flushing your weight gainer down the toilette, you should really reevaluate your personal and training goals. For an athlete whose exercise bouts are long and frequent, carbohydrate repletion may well turn out to be beneficial. If not for muscle growth, then for performance maintenance. A general demonization of carbs would thus be similarly inappropriate as the "fat scare" of the late 20th century. It all depends on who you are and what your athletic and aesthetic goals are.

AKG as in Arginine Alpha-Ketoglutarate for GI Health

For many of us, our gut is like our feet. We ignore it as long as it appears to be working properly. I think, I do not have to tell you that this is a mistake. Just like you cannot run without healthy feed, you cannot digest and use all the good food and supplements you consume without a healthy gut. This is why you should be interested in the findings of a recent review by scientists from the Hubei key Laboratory of Animal Nutrition and Feed Science in Wuhan 430023, China (Hou. 2011).


The scientists evaluation of related studies lead them to conclude that the conversion of Alpha-ketoglutarate (AKG), which is an intermediate of the Krebs cycle and bridges amino acid metabolism with glucose oxidation, into glutamate in the gastrointestinal tract of humans and animals is of particular interest in view of overall gastric functioning, "including regulation of cell function, neurotransmission, and gastric emptying".

Translating the basic research into practice, results of recent studies indicate that dietary supplementation with AKG alleviates oxidative stress and injury in intestinal mucosal cells, while improving intestinal mucosal integrity and absorption of nutrients in endotoxin-challenged pigs.

If you do not find that exciting, you might be interested in AKG's effect on mTOR-signaling (largely regarded as one of the fundamental triggers of protein synthesis and "muscle growth"):

The beneficial effects of AKG are associated with increased activation of the mTOR signaling pathway and net protein synthesis.

So, in view of the disappointing news on the inability of Arginine-AKG to raise nitric oxide levels, it may come as a surprise that it may have a distinct value far apart from muscle pumps and popping veins.

1.86 g EPA + 1.5g DHA Augment the Hyperaminoacidemia-Hyperinsulinemia–induced Increase in the Rate of Muscle Protein Synthesis

MPS, the acronym for "muscle protein synthesis", certainly is an eye-catchers for everyone interested in building sleeve bursting arms. Obviously, the at which (dietary) proteins are incorporated into muscle tissue is an important factor in how much and how fast your muscles will grow.

Scientists from the Washington University, School of Medicine (Smith. 2010) have now conducted a randomized placebo controlled trial on the effect of omega-3 (4g/day Lavazza(TM) = 1.86 g EPA + 1.5g DHA) supplementation on muscle protein synthesis in older adults. And despite the fact that omega-3s on their own had no effect on  MPS, the consumption of supplemental omega-3s significantly augmented the MPS-response to Hyperaminoacidemia and Hyperinsulinemia.

Figure 1: Mean (6SEM) concentrations (arbitrary units) of mTORSer2448 and p70s6kThr389 during basal, postabsorptive conditions and during the hyperaminoacidemic-hyperinsulinemic clamp before and after 8 wk of supplementation with either corn oil (n = 7) or omega-3 fatty acids (n = 8). (Smith. 2010)

The results of this study may also shed some light on a 2003 study by Fearon, et.al. (Fearon. 2009), who found that adding fish oil to a protein supplement increased lean mass gains in patients with cancer cachexia.

While, in view of these results, adding some fish oil caps to your post-workout protein + carb drink  seems to be a beneficial, yes, almost obligatory idea, I personally feel that the verdict on the effects of fish oil (especially in particularly high doses) in healthy, or even athletic parts of the population is still out there. Anyway, I will keep you posted.

On a side note: Notice that this study uses a much more "favorable" (my point of view), low EPA:DHA ratio compared to the study I reported on a few days ago, which found no influence of fish oil supplementation on weight and fat loss in obese individuals.