Friday, April 5, 2013

Four Weeks "On" Two Cans of Energy Drink = 6.6% Increase in Body Fat + Other "Adaptations" in Healthy Men & Women

Contrary to regular coffee, the majority of energy drinks ensures that you get your daily (over-)dose of diabesity promoting sugar - so, no need for additional white poison.
If you are following the SuppVersity news closely, I am sure you will remember the note on the carcinogenic, or rather "breast cancer risk increasing" effect a single cup of soda per week can have (read more). As a follower of the SuppVersity Facebook news, you will also remember that these effects could potentially be brought about by the hormonal chaos that's brought about by these sugar sweetened beverages (learn more; Schliep. 2013).

Now, these results, as well as the accumulating evidence that sugar sweetened beverages in general and high fructose corn-syrup laden sodas are among the, if not simply the #1 contributer to the rise of the obesity pandemic, certainly raise the question what exactly it is that happens to us, when we consume these delicious* yet deadly elixirs on a daily basis (*personally I lost my appetite for soda years ago... along with the fat covering my abs, by the way).

4 weeks of sugar sweetened beverages and our bodies helpless effort to adapt

You've already gotten a first peek at what happens, when we make these unsatiating calorie-bombs a staple of our diets in a previous Suppversity article from June 30, 2012, in which I exposed the truth behind the shockingly simple formula "2 Energy Drinks per day = +1kg of Body Fat in 4 Weeks" (read more).

Nutritional composition of the SSB
Aside from the effects on the body weight, the 2012 study by Sartor et al. did yet not allow much insights into the corresponding metabolic changes, the bodies of their volunteers underwent. It is exactly these changes, or "metabolic adaptation" as (sounds quite positive, doesn't it) as the researchers call them, Francesco Sartor and his colleagues were now trying to elucidate in a follow-up study.

Would you be willing to gain one kg of pure fat for $150?

To this ends, the researchers from the College of Health and Behavioural Sciences at the Bangor University in the United Kingdom and their colleagues from Italy and the US recruited another 11 subjects who had been cherry picked for their low sugar sweetened beverage (less than 500ml SSB per week) intake from a group of 213 candidates, all of whom wanted to qualify for the £100 upon completion of testing as compensation for their time.

Yeah, I know, obviously Sator et al. were not really honest with these 5 men and 6 women. After all, the scientists knew in advance that they would also be compensated for the ill health effect the consumption of ~760 mL/day of Lucozade Sport would have on their metabolic health.
"Before and after the intervention, body composition, respiratory exchange ratio (RER), insulin sensitivity, muscle metabolic gene and protein expression were assessed. Adaptive responses to hyperglycaemia (7 days, 15 mM) were tested in primary human myotubes." (Sartor. 2013)
I guess few of you will be surprised by what they are just about to see in the selected data I plotted for you in figure 1. And if you are honest, what we are seeing here is - at least in parts - actually an adaptive response.
Figure 1: Body composition, HOMA data, glucose / insulin levels, substrate oxidation, blood lipids and skeletal muscle mRNA expression relative to pre-"supplementation" levels (Sartor. 2013)
I mean take another look at the changes the scientists observed in vivo (11 subjects, 4 weeks on SSB) and in vitro (human muscle cells incubated with 15 mM glucose for 7 days; model of hyperglycemia). Despite all their desperate efforts, including
  • the increase in fat mass (+1kg) that's meant to stash away the glucose that would otherwise start to form a gluey lining on the cell walls and 
  • the concomitant increase in the respiratory exchange ratio (RER), which does allow for a greater oxidation of glucose (obviously at the expense of fat), 
the subjects, or rather their bodies, were not able to to ward off the statistically significant +0.3mmol/L increase in fasting blood glucose. Moreover, the changes in protein expression scientists observed in the muscle cells they had isolated from the quadriceps muscles of the participants, namely the increased activity of the glycolytic enzyme GAPDH and the corresponding decrease of PGC-1alpha in the musculature of the previously healthy subjects are yet less "logical" (=expedient).

The Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) induced increase in glycolysis (see schematic drawing over @Wikipedia) does not suffice to reduce the amount of glucose that's floating around while it contributes to the decrease in fatty acid oxidation that is further promoted by a decline in PGC-1a activity and thus the ability to handle the increased triglyceride load by burning the glycerol + free fatty acid ethers in the mitochondrial power plants of the subject's skeletal muscle.

MondaA, a "bad guy" to remember?

Against that background, it i not really surprising that the scientists did also observe an unwanted but in a way still "adaptive" (=reactive) increase in insulin resistance - an effect of which the researchers believe that it was brought about or at least facilitated by increased amounts of the glucose sensing protein MondoA:
This may be the right time to read up on the SuppVersity article about previous study by Sartor et al. "Fat Content Per Energy Drink 0g, Body Fat Gain Per Energy Drink 18g!" (go back)
"Glucose sensing in skeletal muscle cells, as part of a mechanism for the maintenance of cellular energy homoeostasis, has been demonstrated to be strongly dependent on the transcription factor MondoA.

MondoA seems to be a master regulator of glycolytic genes and indeed it activates the transcription of numerous genes encoding metabolic enzymes.. Glycolytic gene expression is highly upregulated in response to MondoA recruitment from cytoplasm to nuclei, building a complex with the transcription factor max-like protein x (Mlx), in high glucose conditions. A further target of the Mond-oA:Mlx complex is the thioredoxin-interacting protein (TXNIP). TXNIP impairs peripheral glucose uptake stimulating radical oxygen species production.
In short, the increase in MondoA protein content is directly and mechanistically involved in the etiology of a metabolic vicious circle, which is at the heart of the downward spiral that leads from "just being a somewhat chubby sedentary slob" over the "overweight pre-diabetic" right into the emergency room, where the doctors need one of those XXL operating tables, when they are trying to save the lives of people with SSB consumptions of 3-4L per day.


Bottom line: I suppose that many of you will now be thinking. So what, I knew all that already; after all, I just got to look around and see all those SSB victims driving around in their cars. Nevertheless the details you may have learned about the enzymatic roots of the metabolic dysregulation that occurs with the consumption of "only" 2 cans of a "soda-like" sports drink per day are not the main message of the study at hand.

As of now, there is no published in vivo evidence for the beneficial effects glutamine may have on the MondoA-induced dysregulation of glucose homeostasis, but there is an interesting 2009 paper by scientists from University of Utah suggesting that the reduction in glucose uptake due to MondoA (over-)activation in the presence of high glucose levels may be ameliorated / abolished by glutamine (Kaadige. 2009) and a study that confirms the beneficial effects of glutamine on insulin sensitivity (read more).
From a mere scientific perspective, the news is the shockingly short time span in the course of which perfectly healthy, lean and reasonably active individuals can develop all the characteristics scientists have hitherto thought of as a result chronic hyperglycemia. A particular focus of future studies should now be on the time-course of the change in MondoA expression, as well as means to prevent and reverse the deteriorations of this "metabolic glucose sniffer".

Theoretically glutamine could be a potential candidate, as it has the ability to block the MondoA induced, glucose dependent activation of the thioredoxin-interacting proteinin and the subsequent blockade of glucose uptake. And while respective research on this mechanism is not yet available, those of you who have been around ever since the early beginnings of the SuppVersit, may remember the 2010 post on the "Positive Effect of L-Glutamine on Insulin Sensitivity" (read more) - who knows, maybe it is mediated by the blockade of the transcriptional activity of MondoA at the TXNIP promoter (see figure on the right)!?

References:
  • Kaadige MR, Looper RE, Kamalanaadhan S, Ayer DE. Glutamine-dependent anapleurosis dictates glucose uptake and cell growth by regulating MondoA transcriptional activity. Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14878-83.
  • Schliep KC, Schisterman EF, Mumford SL, Pollack AZ, Perkins NJ, Ye A, Zhang CJ, Stanford JB, Porucznik CA, Hammoud AO, Wactawski-Wende J. Energy-containing beverages: reproductive hormones and ovarian function in the BioCycle Study. Am J Clin Nutr. 2013 Mar;97(3):621-30.
  • Sartor F, Jackson MJ, Squillace C, Shepherd A, Moore JP, Ayer DE, Kubis HP. Adaptive metabolic response to 4 weeks of sugar-sweetened beverage consumption in healthy, lightly active individuals and chronic high glucose availability in primary human myotubes. Eur J Nutr. 2012 Jun 26.