High or Low Protein? Milk, Whey, Casein or Soy? In the End It Could Make Less of a Difference Than You Thought!

Image 1: All macronutrient ratios aside, my gut tells me that I cannot go wrong with something as delicious as a piece of steak (img. picturesdepot.com) - I don't know if that is what scientists call the "gut brain axis", though *lol*

At least those of you who make sure, they get their daily dose of SuppVersity news should actually remember the "Bray study" (cf. "A Tale of Macro- and Micronutrient Modifications"), i.e. the methodologically exemplary, yet with respect to the underlying research question "What happens if you add 40% of additional calories in form of protein, fat or carbs to a high carb diet?" somewhat questionable overfeeding study the results of which caused quite a stir within the blogosphere and even mainstream media.

And contrary to what you may have read elsewhere, the fundamental message of the study, and I am not growing tired of repeating that, was a) "Consume more energy (not calories) than you need (not expend ;-) and you will get fat" and b) "Consume it from protein and you will get just as fat, but still gain some muscle."

Now, if we take these results and try to predict the results of a complementary experiment, in which people would be fed -40% less than their regular diet with either high or normal protein content, we would expect that a) the fat loss would be identical (remember! we use the results of the Bray study, not common wisdom as the basis of our predictions) and b) the high protein group should be able to maintain more muscle mass - right?

Caloric deficit determines weight loss in obese rodents, irrespective of protein intake

Although a pertinent (similarly well-controlled!) human study is still not available, a study that has just been published in the International Journal of Obesity does suggest that - at least in obese rodents - the above prediction does not apply (Chevalier. 2012). Although the 56 male Wistar rats in Chevalier et al.'s trial did lose identical amounts of body weight on a 3-week dietary intervention with a -40% reduced energy intake, they did not retain more muscle mass, when the diet contained 33% instead of only 12% of protein (cf. figure 1)!

Figure 1: Muscle and body fat mass of the rodents after 5 weeks on a obesogenic diet  and another three weeks on the same diet (obesity induction, ad libitum), or a diet with a -40% reduced energy content and identical macronutrient composition (OI-R) or a +20% greater protein content from either milk protein, whey protein, casein, casein + whey (50/50) or soy; the data is expressed relative to animals who were maintained on the ad libitum obesity induction = energy dense diet (blue bars = 100%; data calculated based on Chevalier. 2012)

And, as you can infer from the legend in figure 1, the major source (milk, whey, whey + casein, casein or soy) of the dietary protein in the diets did not exert any statistically significant influence on the total or relative (subcutaneous vs. visceral) body fat loss and the mass of the gastrocnemius or soleus muscles of the rodents, either.

When protein supply is low "protein recycling" kicks in

If you take a closer look at the data in figure 1 you  may notice another unexpected result (figure 1, red arrow). Not only were the rodents on the calorie reduced 12% protein diet able to maintain just as much muscle mass as their peers on the obesogenic ad-libitum diet (dark blue, left reference bar in figure 1), it does even appear that they experienced the same statistically yet non-significant "muscle growth" in the soleus as the rodents in the high protein groups.

Figure 2: Relative macronutrient (left) and absolute (in g/100g) main ingredient (right) composition of the experimental diets (data calculated based on Chevalier. 2012)

While there are probably a whole host of explanations for this, from a statistical point of view, non-existent phenomenon, I personally would assume that it is a combined result of an increase in food-seeking behavior (and a subsequent "training" effect which would obviously be more pronounced in the soleus, an "endurance" muscle, than the gastrocnemius) and an increase in "protein recycling".

Figure 3: Total protein content, fraction (FSR) and absolute (ASR) protein synthesis in liver, muscle and kidney tissue of the animals in the diet groups (data expressed relative to ad-libitum group, left) and ubqituitin mRNA expression in skeletal muscle of the rodents in all groups (right; data calculated / adapted from Chevalier. 2012)

Both the (within statistical margins) identical total protein contents, fraction and absolute protein synthesis rates in liver, muscle and kidney of the rodents (cf. figure 3, left), as well as the profound upregulation of the ubiquitin protein mRNA expression which showed a similar pattern in liver, kidney and muscle tissue (figure 3, right shows the data from the muscle samples) are indicative of the existence of protein sparing mechanisms which are triggered in response to a low(ish) protein intake. Despite its overall proteolytic activity, the physiological function of ubiquitin is after all to degrade and recycle unnecessary protein in the cell and has consequently received some attention as a potential target for cancer therapy (and prevention) in the last couple of years (Hoeller. 2009).

Bulking or dieting, lean or obese - different rules apply and generalizations are not advisable

Aside from the fact that this obviously is another rodent study and whenever the results of these studies do not conform with someones current dietary paradigm, the main argument will be that "rodents are no little human beings" (I don't know if you did notice that the same people usually rely on rodent studies to support their own argumentation ;-), there are a few other things to consider, before you flush your protein shakes down the toilette.

1. The rodents were obese: It does make a huge difference if you have more than enough body fat to get you through a 3-week phase of relative profound (-40%) caloric restriction, or if you are already lean and want to shed the last pounds of body fat that cover your perfectly sculpted six-pack. If the former is the case - and I have pointed that out in previous blogposts, e.g. "Goal Setting and Stock Taking on a Diet" - your energy intake will be the main determinant of your weight loss. Modulated, if anything by your carbohydrate intake, which can hinder weight loss as long as you are pathologically insulin resistant (when you have achieved a decent degree of leanness, on the other hand, the exact opposite will be the case!)
    
2. Rodents are in fact no small human beings: While it is simply stupid to discard all rodent data (that is not to your liking) with the argument that "rodents are no small human beings", there still is the issue of compliance, which - as we have seen in "High Carb vs. High Fat for Obese Type II Diabetics and What Really Happens, When Science Meets Real Life" - still is one, if not the major obstacle to successful weight loss and maintenance, where the satiating effects of a high protein intake and milk proteins, in particular (Lorenzen. 2012), will certainly come handy - assuming that the dieters actually adhere to their high-protein diet and don't simply return to their regular dietary habits, as it was the case in the Krebs study. Whether soy is or is not an option to achieve this "high" protein intake, is yet probably a question of faith and the potential risks you want to take (no soy for me, though).
    
3. The caloric reduction (-40%) was very pronounced: I have likewise pointed out in various previous posts related to successful long-term weight loss that both scientific evidence, as well as practical experience suggest that energy restrictions >30% are of no use, if the goal is sustainable long-term weight loss (they may yet very well be indicated in morbidly obese persons). And while sustainability is of little importance in the context of the study at hand, the -40% reduction in energy intake also masked the small, yet still beneficial effects a high(er = not >50%!) protein intake exerts on the resting energy expenditure of dieters (Keller. 2011)
    
4. Update - Not enough protein in one sitting: A few lines further down I wrote that I would suspect that you, my dear (and smart) readers would probably be able to come up with at least three additional confounding factors - and what shall I say? Proud Daddy just came up with #4! In view of the fact that the protein synthetic effect of protein depends largely on the size of an individual meal (in humans >20g of quality protein, or 10g+ of EAAs; cf. "Never Sip Your Whey!"), confounding factor #4 is that rodents usually don't eat just  2-3 large meals and thusly probably consumed relatively low amounts of protein per meal, even in the high protein group.

I guess, if you spent some more time thinking about possible confounding factors, you would come up with at least another three points that speak in favor of a reasonably high protein intake. One I personally would not measure in percentages, but rather in grams: Starting with a baseline protein intake of ~1.5g/kg body weight and building the rest of your diet around that, a 1,600kcal high protein diet for a 200lbs person could consist of ~150g protein, 50-100g fat and 50-150g carbs (the leaner, the more active and the less insulin resistant you are the more carbs). And please remember: This is just a sample calculation, so please deny yourself comments like "but is that not way too little protein?" - specifically, because this kind of "if high is good, higher must be even better" and "protein is the only save nutrient" logic could well be the reason why your weight loss is stalling.