Friday, January 6, 2012

A Tale of Macro- & Micronutrient Modifications: Eating "Unlimited Protein" Will Make You Fat. A Hypercaloric Low Protein Diet With a Large Amount of Arginine Won't!

Image 1: The main message of the Bray study (according to Bray himself is) that you won't get away with consuming way more energy than you need - no matter how much of this energy comes from protein.
Even if you have not read it on the SuppVersity Facebook page, or in the comment section of one of the previous posts, I am sure that most of you all will have heard, or rather read, the fuss people have been making about getting away with "eating unlimited amounts of protein". Now, although, I know that you, as an educated SuppVersity reader would not fall for b***s*** like this, I still feel inclined to at least refer you to the surprisingly good summary, Dr. George A. Bray, the author of the study which triggered the recent upheaval (Bray. 2011), provides in his JAMA Video interview on YouTube. The main take home message you should remember is: "Fat gain is primarily a function of calories" - the subjects in all three groups (5%, 15% and 25% protein) gained, within the statistical margin of error, the same amount of body fat.

The nitty gritty on overeating: Eat 140% of the energy you expend and get fat - no matter what!

The one difference a higher protein intake on a hyper-caloric diet makes - and I am certain that you will have been aware of that - is that overeating on protein will help stimulate muscle protein synthesis and thusly facilitate increases not only in fat, but also in lean mass. Now, while this obviously is a good thing (compared to gaining fat, only), you should be aware that "gains" like that won't be particularly aesthetic. After all, even the subjects in the high protein group gained more fat than muscle and though the difference was statistically insignificant, the mere fact that you have more muscle than fat tissue should tell you that your body fat percentage increases even if you gain identical amounts of fat and muscle weight. So, I guess that the average participant of the Bray study was probably not very pleased with the way he looked when the study was over.
Figure 1: Composition of the diet of the participants at baseline and during the 8 week intervention period (left); lean body mass and fat mass (in kg) of the participants before and after the intervention (right; data calculated based on Bray. 2011)
So, if a simple increase in the protein to fat + carbohydrate ratio won't suffice to make sure that the weight you are gaining on your hyper-caloric diet, is not fat weight, what else may help? Well, the results from another recently published study by Christoffer Clemmensen et al. may provide at least a hint to another adjustment that to our dietary regimens that could make a difference, a modifications at the micro- not the macronutrient level...

An arginine rich low protein diet builds muscle, and melts away body fat

Allegedly, this is only another rodent study, but hey, haven't we been able to predict the outcome of the Bray study based on previous data from rodent studies, as well? Yes, we have! So, bear with me, because the effects the 10% total protein, of which ~8% came from casein and 1.8% from supplemental l-arginine (cf. figure 2) had on the body composition of the 6 week-old mice in the Clemmenson study, were pretty astonishing (Clemmenson. 2011).
Figure 2: Macro- and micronutrient (protein component) composition of the diet the control and arginine groups of the Clemmenson study were fed in the course of the 10-week intervention period (Clemmenson. 2011)
Contrary to previous studies, where the effects of l-arginine have mostly been tested in rodent models of diabetes or other (human) metabolic diseases, the mice in the Clemmenson study were perfectly healthy. After a 2-week acclimatization period at the lab, they were simply put on one of the two low-protein (8% basal + different amino acid mixes, cf. figure 2) diets and judged by their weight development over the 10-week study period (cf. figure 3, right) the effects appear to be negligible.
Figure 3: Additional cumulative energy intake over 21day and 72h period, as well as reduction in feed efficiency in l-arginine fed mice over 21day period (left); total body weight over the course of the whole study (right; data based on Clemmenson. 2011)
Things are becoming increasingly interesting, though, when we also take into account that the mice on the arginine diet consumed more food, so that their "feed efficiency" that it the amount of weight they were gaining per gram of food they were consuming was profoundly reduced (-48%, cf. figure 3, left). What is yet more important than a reduced "food efficiency", which by the way is the fundamental working principle of stupid "weight loss pills", such as the "fat blocker", Alli, was that the low-protein, "high" arginine diet did in fact have the effect that was falsely ascribed to the "high protein" (who says 25% is high?) diet in the Bray study. It lead to a greater increase in muscle over fat mass compared to the "normal" diet, despite a ~15% increase in total calorie intake (cf. figure 4)
Figure 1: Body composition and fat weight of mice after 10 weeks on normal and high l-arginine diet low-protein diet (data based on Clemmenson. 2011)
Although this effect could partly be explained by an increase in energy expenditure in the absence of statistically significant changes in total activity levels, the absence of measurable increases in UCP1 and UCP2 (uncoupling proteins the activity of which will make a metabolism "waste" more energy in form of heat) suggests that another, more significant effect of the low-protein, "high" l-arginine diet may be the driving force behind these beneficial changes in body composition.

Micronutrient (l-arginine) mediated modulation of insulin sensitivity as a key to lean gains

Figure 5: As the correlation between fat mass and basal insulin levels shows, getting fat has little to do with the amount of insulin in your blood, but everything with the way your body reacts to a given amount of insulin. That the latter is not determined by total protein intake, but by refinements in the micronutrient composition, should make you reconsider if "how much protein should I eat?" really is the most important question to ask.
As it turns out, this driving force is in fact an old acquaintance: insulin! Or rather the arginine-mediated increase in insulin sensitivity about which the scientists write:
OGTT and ITT, performed at week 8 and 9, respectively, demonstrated that L -Arg supplemented mice were signifi-cantly more glucose tolerant (34% reduction in AUC, P < 0.03) and insulin sensitive than mice on the control diet. Fasting blood glucose levels were significantly lower in the L -Arg supplemented group (7.9 ± 0.4 mmol/L) compared with the control group (9.7 ± 0.2 mmol/L, P = 0.003), but basal plasma insulin concentrations after 10 weeks on the diet did not significantly differ between the two groups
Now, don't get me wrong (I know you will ;-), I am not saying that eating a low-protein diet with "huge" amounts of l-arginine in it (the human equivalent, by the way, would have been ~0-8g/kg body weight) is going to turn you into a ridiculously ripped mass monster. I am just trying to make a point that we are only scratching the surface, when we focus solely on the "good protein", the "bad carbohydrates" or the "good and bad fats"... and that the body fat of the mice in the Clemmenson correlated with total insulin only in the "control", yet not in the l-arginine group (cf. figure 5), goes to show that even the contemporary vilification of insulin will probably have to be re-evaluated in light of the effects the identical levels of insulin can have on the body composition and other important health factors in different dietary contexts, individuals and probably even time-points.
Note: As soon as I find the time I am going to write something more comprehensive on the whole "how much protein is enough and when can it even become detrimental"-issue... promise ;-)
So, before you jump aboard the boat of any "unlimited whatever" nutritional strategies, you better focus on the myriad of small adjusting screws, which will all have to be in place to optimize firstly your health and if that is in place, secondary your performance or body aesthetics.... and I guess, I don't have to remind you that the SuppVersity is the place to go for your daily dose of information that will help you not to "screw up" ;-)