Thursday, December 27, 2012

The Protein Leverage Hypothesis

Back in 2006 I stumbled upon the research of Dr. Stephen Simpson and wrote Again It's the Protein, highlighting the findings from a small study that looked at protein requirements and how altering protein density in the diet may effect consumption of calories. 

The study was borne from the Protein Leverage Hypothesis, authored by Simpson and his colleague David Raubenheimer in 2005. I found it after reading the above study data and have remained intrigued by the concept ever since.

Briefly, the Protein Leverage Hypothesis (PLH) holds that our protein requirement influences our consumption of food, with excess carbohydrate and fat consumed to meet requirements when foods provide low protein density, and less consumed when foods are protein dense.  


Their mathematical model was formed from data in animal studies that found various insects and mammals regulate total consumption of food around protein requirements - in poor protein environments, excess is consumed to meet requirement, and in protein rich environments too little is consumed to meet energy requirements.  Their emphasis was that protein - what we tend to ignore in our diets because it remains fairly constant - is prioritized over fat and carbohydrate, and the changing dietary landscape of foods provides for less protein, leading to over consumption to meet requirements.

In their paper above, they laid out four scenarios that look at the implications if protein is indeed prioritized over fat and carbohydrate.

1. There is a shift to the diet containing a higher percentage of carbohydrate and fat

This could occur where fat- and/or carbohydrate-rich foods are more accessible, more affordable, in greater variety, or more palatable than alternatives, leading to people effectively being trapped on a suboptimal diet. Under such circumstances, maintaining the amount of P eaten requires over-consumption of C+F.

2. There is a shift to the diet containing a higher percentage of protein

If the diet contains a higher percentage of P, yet the absolute amount of protein eaten is regulated to the intake target, the result will be that C+F intake will fall, bringing the body into energy deficit and leading to weight loss.

The example noted, [a]n increase of 1.5% in dietary P from 14% to 15.5% results in an 11% decrease in C+F eaten.

3. There is an increase in the requirement for protein

If diet composition remains unchanged, yet protein requirements increase, then over-consumption of C+F will result. Shifting the intake target ratio from 14% to 15.5% P in the diet leads to a 13% increase in C+F eaten – with attendant risks of weight gain.

They provided the following example as to how such might occur - [o]ne source of protein loss is hepatic gluconeogenesis, whereby amino acids are used to produce glucose. This is inhibited by insulin, as is the breakdown of muscle proteins to release amino acids, and therefore occurs mainly during periods of fasting. However, inhibition of gluconeogenesis and protein catabolism is impaired when insulin release is abnormal, insulin resistance occurs, or when circulating levels of free fatty acids in the blood are high. These are interdependent conditions that are associated with overweight and obesity, and are especially pronounced in type 2 diabetes. It might be predicted that the result of higher rates of hepatic gluconeogenesis will be an increased requirement for protein in the diet. Unless either more high-P, low-C+F items are included in the diet (i.e. scenario 2), or rates of removing excess co-ingested C + F are increased, weight gain will occur. And the system becomes unstable – further increases in fat deposits [especially abdominal fat ] will increase protein needs further, which will drive even greater weight gain.

4. Diet remains unchanged but exercise levels decline


For this we find, 


It seems that while humans respond by increasing intake following very high levels of energetic expenditure, we are less responsive to lowered needs. One interpretation is that our intake target and the associated regulatory mechanisms controlling food intake have evolved to assume a certain level of non-protein energy expenditure. But if this energy is not actually expended, the excess is stored as fat. [...] Therefore, the result of lowered levels of exercise is, in effect, to lower the position of the intake target on the C+F axis, while causing P requirements to increase (scenario 3). Unless the diet changes towards a higher percentage of P, the result will be weight gain.

They noted,

"The scenarios introduced above are not independent. Either shifting the diet composition to a lower percentage of P (scenario 1), or effectively doing the same by having low levels of energy expenditure (scenario 4), will result in over consumption of carbohydrate and/or fat to maintain protein intake. This in turn will predispose towards weight gain and lead to disinhibition of gluconeogenesis, which will increase protein demand (scenario 3). Unless this increased demand is met by selecting high-P foods, protein appetite will drive increased intake of C + F, resulting in further weight gain, and so on in a vicious cycle leading to obesity and its associated diseases."

In their conclusions, they wrote,

"The key assumption upon which our hypothesis resides is that when humans are forced to trade-off protein intake against that of carbohydrate and fat on nutritionally unbalanced diets, physiological regulatory mechanisms prioritize protein. If this is true, then all else that we say must follow – it is a mathematical inevitability. [...] Given the implications that follow from our hypothesis, we would suggest that this is a vital subject for future research in human nutrition. In reference we suggest the design of such experiments. Finally, our ‘vicious cycle’ provides a candidate-positive feedback mechanism for the spiral into morbid obesity. It predicts a key role of hepatic gluconeogenesis in the development of obesity."

To say I was intrigued, is an understatement; while the paper had its flaws, the concept had merit and had been validated in various animal models.  Additional study would hopefully bear fruit and further refine the concept or have it dismissed as yet another dead end in nutrition research.

In the years since, there have been a number of trials designed to test the PLH, and I'm in the middle of reading through some, but wanted to post this to whet your appetite before I dig in and take a look at those studies and the findings.  The above is the prelude, to give you information about the posts I'll make in the coming week, so you have the background information to work with the data I'll go through!

28 comments:

  1. Looking forward to the next installment, which I predict is going to be better than the focus on Jimmy Moore lately. I lost interest in his brand of crazy a long time ago and would much rather read this type of thing than stuff about him doing his crazy schtick.

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  2. Anonymous10:18 AM

    "Finally, our ‘vicious cycle’ provides a candidate-positive feedback mechanism for the spiral into morbid obesity. It predicts a key role of hepatic gluconeogenesis in the development of obesity."

    I would think that begins to define why a low-carb diet works as it does; it may not be the carbohydrate, but the higher level of quality protein expected in the diet? And since we're eating protein over carbohydrate, then the calorie deficit makes sense too, at least to me.

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  3. LowCarb Me10:57 AM

    That explains a lot about why a lowcarb diet might work as well as it does for so many.

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    1. If nothing else, it does lend support to the satiety experienced in a low-carb diet, which is also partly explained by the role of PPY and CCK; it also lends support to why, even if one keeps carbohydrate low, weight gain may be predicted if protein intake is not modified to requirements at a lower weight once one loses weight. To me it's very interesting stuff and expands things well beyond just calories, and takes a direct hit on nutrient-density, in this case, EAA requirements.

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    2. Mary C1:20 PM

      So would that mean that one could eat pretty much however they like as long as they eat their protein and maintain an energy balance?

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  4. Anonymous11:27 AM

    It certainly would explain why Jimmy Moore gained weight even with lowcarb. He overate fat in the equation.

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    1. Anonymous11:34 AM

      Are we really going to start in on Jimmy again? As much as I wish he'd fade away influence wise, I don't think he's the subject of this article, so bringing him into it just to bash him is getting stale.

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    2. I agree, let's keep on topic, the post is no about Jimmy - not even by implication.

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    3. Anonymous1:21 PM

      Oh, but it's fun to make fun of Jimmy and his extremes!

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    4. Anonymous9:20 PM

      *Never* a bad time to call out Jimmy's shenanigans.

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  5. Sounds like the obesity issue is still energy in/out but the way in which that results is the cause of excess intake.

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    1. One of the things we need is an explanation of "why" people consume excess energy when they seemingly know better; we know it's not simply a moral defect (gluttony, sloth), so what is it? What would cause an otherwise intelligent person to eat more than they need? That's why I find the PLH very intriguing - it does offer an explanation that we can look into further to understand the potential "why" role of protein.

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    2. Anonymous10:09 AM

      "If the diet contains a higher percentage of P, yet the absolute amount of protein eaten is regulated to the intake target, the result will be that C+F intake will fall, bringing the body into energy deficit and leading to weight loss". :)


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  6. Anonymous1:14 PM

    Would there be a difference if the protein is lean or fatty?

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    1. This comment has been removed by the author.

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  7. I just read the PDF of the paper. Very interesting!

    Here is the link if anyone wants to see more than the abstract linked above.

    http://insects.tamu.edu/REU/ARTICLES/SIMPSON-2005-OBESITY%20THE%20PROTEIN%20LEVERAGE%20HYPOTHESIS.PDF

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  8. Probably why so many also have success on a Paleo/Primal diet, lots of quality protein.

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  9. For weight loss etc your protein most important to work out then fat and carbs according to Alan Aragon:
    http://www.livestrong.com/article/553149-healthy-eating-101-improve-your-fat-loss-and-muscle-gain/

    "Hitting your goal for the day is the most important aspect of eating protein, whether it’s for fat loss, building muscle, or just maintaining your weight."

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    1. Alan has some good things to say but he often doesn't get it. He said:

      "Still, while carbohydrates technically are not essential, you do need them when living an active lifestyle. Not to mention, fruits and vegetables are two of the most important sources of carbohydrates, and both provide nutrient-rich calories that protect against disease...Generally speaking, if you’re active you need anywhere between one to three grams of carbohydrate per pound of lean body mass."

      This is nonsense. You do NOT need carbs in order to live an active lifestyle. I agree that veggies (not necessarily fruit) should be a part of most peoples diets since few people eat organ meats and varied sea foods.

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    2. even your 'experts' clearly agree at a certain level you must increase carbs..you even asked Rob about it..

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    3. I know Robb says this but he's talking extreme levels of exercise which few people do. Ask an Iditarod dog.

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    4. Ask an Iditarod dog.

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  10. EV Lynne10:56 PM

    Regina, comment on Jimmy Moore and the neo-Nazis?

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  11. Things present themselves to you, and it's how you choose to deal with them that reveals who you are. We all say a lot of things, don't we, about who we are and how we think. But in the end it's your actions, how you respond to circumstance that reveals your character.
    -Cate Blanchett

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  12. EV Lynne9:54 PM

    Brutal. But I can almost guarantee it will go right over Jimmy's head.

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  13. Wow. This makes so much sense to me. I've been trying to figure out lately why I tend to eat less on the days when my husband doesn't work, and more on the days when I'm home alone.

    We always eat a high protein breakfast by 8:00 a.m. when he's home. That breakfast is generally so filling that we often just have a very small lunch, and then a normal-sized dinner.

    When he's not at home, I'm more apt to be working, and putting off eating breakfast until later. But when I do eat, it's not as high in protein as it is when he's there. It's relatively small in protein. Lately, I've been returning to the kitchen again and again throughout the day and thinking there was something psychological going on.

    But maybe not. I think I'm going to start eating the way I do on the weekends and see what happens.

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  14. I've been posting on the Protein Leverage concept in a similar vein at http://www.unamericandiet.com/2012/11/the-protein-leverage-hypothesis.html

    I try to be responsible and science based, like your good work here, so thought you might enjoy,
    -Iggy

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