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.
"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!