Protein Leverage & Obesity
You have probably heard before that protein is more satisfying than other macronutrients.
And at least in some trials, the impact can be pretty impressive.
For example, when participants were placed on a 30% protein diet for two weeks, their mean energy intake dropped spontaneously by 441 calories per day, which was accompanied by more than ten pounds of weight loss, compared to when they ate a 15% protein diet.
But why this is the case is the subject of ongoing debate. Back in 2005, Simpson and Raubenheimer hypothesized that we have evolved a specific appetite for protein, since amino acids are the building blocks of life, and protein tends to be a little harder to come by than the other macronutrients. Thus, when we eat a lot of protein, we are satisfied sooner, and if we do not consume enough protein, our hunger ramps up to make up the difference. The latter situation poses a serious problem in the context of a diet that is “diluted” by fat and carbohydrates (like the modern food environment), because we are more likely to overeat in order to meet the protein target. Another way to think about it is that if you’re presented with a menu that contains only 10% dietary protein, you’re going to need to eat more food (and likely more calories) to get a similar dose of protein, compared to one with 20% dietary protein.
The researchers backed this idea with population-level data: According to nutrient availability estimates from the FAO, dietary protein content in the US decreased from 14% of total energy in 1961 down to 12.5% in 2000. Doesn’t sound like much, right? But if we assume that some homeostatic mechanism is trying to keep absolute protein intake roughly the same, that would mean that people would need to increase their fat and carb intake by 14% to maintain the same number of grams of protein. Since fat and carbs contain 9 and 4 calories per gram respectively, that would mean inevitable weight gain, barring increased energy expenditure. And indeed, Kevin Hall at the NIH found that such a small decrease in the protein fraction of the food supply could result in relatively large increases in energy intake, and explain at least part of the obesity epidemic.
I’ve been curious about this idea for a while, but never really took a deeper dive, so let’s take a look together.
This Week’s Research Highlights
🍊 In a controlled setting, lowering the protein content of the diet results in higher total energy intake.
Researchers recruited 22 lean participants from the Sydney region and had them stay at the lab for three different 4-day long periods. During each experimental window, they were offered a menu with similar food items, but the recipes were carefully adjusted to contain either 10%, 15%, or 25% of energy as protein, and matched for energy density and palatability. At the end of the study, all subjects had undergone four continuous days on all of those levels of protein distribution, enabling the researchers to compare the effects of the different levels of protein.
They determined that when the subjects were given a 10% protein diet, they consumed 12% more calories over the four day window, compared to when they were given a 15% protein diet. Most of this energy intake came from snacking between meals. However, going from 15% protein to 25% protein did not alter food intake significantly.
Notably, participants showed a strong preference for savory snacks over sweet while eating the low protein diet. It has been suggested that fat- and sugar-rich ultra-processed snacks may sabotage homeostatic protein-seeking responses due to sharing some of the flavor attributes of protein-rich foods. Which brings us to the next study…
🍃 Cross-sectional data suggests that consumption of ultra-processed food may fuel overeating through protein dilution.
To gain insight into what dietary factors have driven the apparent decrease in dietary protein (and concomitant increase in total energy intake), researchers analyzed dietary data from 9042 participants in NHANES, a nationally representative survey of American residents. They classified all recorded food items according to NOVA, a food classification system based on the extent and purpose of industrial food processing (head here for a decent breakdown of the four levels of processing, since this topic seems to generate a ton of confusion).
Then, the team evaluated the distribution of total energy as well as protein intake according to NOVA processing. They found that more than half of daily energy intake (57.6 %) came from ultra-processed foods, but the average protein content in ultra-processed foods was less than half that of foods in lesser categories of processing.
They determined that higher relative intake of ultra-processed foods was strongly associated with lower relative energy intake from protein. Those in the lowest quintile of ultra-processed food intake had a dietary protein density of 18.2%, while for those in the highest quintile that number dropped down to 13.3%. Furthermore, the reduction in protein density due to ultra-processed food intake was linked to a rise in total energy intake, lending support to the protein leverage hypothesis.
This may simply be a matter of economics – foods with higher protein content tend to be more expensive, and it’s relatively easy to formulate cheap and tasty products that are high in fat and/or carbs.
Fibroblast growth factor-21 (FGF-21) may be a molecular driver of increased energy intake in response to low protein.
Research using rodent models has demonstrated that low-protein diets increase activation of FGF-21 in the brain, leading the animals to eat more overall and to prefer foods that are higher in protein.
To test whether humans respond similarly, researchers (again) recruited 22 lean, healthy participants in Australia and had them stay at the lab for three different 4-day long periods. Similar to the trial described above, they were offered menus during each experimental period that contained either 10%, 15%, or 25% of energy as protein.
When the researchers compared food intake on the protocols, they found that reducing dietary protein intake from 25% down to 10% was associated with a 14% increase in energy intake, mirroring the findings of previous studies. Blood work revealed that this reduction in protein was also associated with a 6-fold increase in plasma FGF-21 levels, as well as a 1.5-fold increase in serum triglycerides.
The researchers hypothesize that FGF-21 may function as an endocrine signal of protein hunger, by acting upon the hypothalamus to boost energy intake. However, this cannot be the whole story for how protein affects appetite. It has been observed that FGF-21 only really operates in the context of a low-protein intake, and its influence is lost in the context of a moderate-protein diet. That means that it could contribute to excessive hunger when protein intake is low, but it wouldn’t really explain why higher protein intake is so satiating. As is always the case, more research is needed.
Random Trivia & Weird News
🦀 Horseshoe crabs (as well as some other critters) have blue blood.
Most vertebrates, including us, rely upon the protein hemoglobin to transport oxygen through the circulatory system. Hemoglobin uses iron to bind with oxygen, and this interaction gives blood its characteristic red color.
Some invertebrates, such as horseshoe crabs, use hemocyanin instead of hemoglobin. Hemocyanin uses copper as its respiratory pigment, and when copper binds to oxygen it appears blue.
This blood also contains some interesting immune compounds that aggressively defend the organism against pathogens, which is why horseshoe crab blood is harvested for medical and pharmaceutical applications, as shown below (whole process looks kind of sci-fi to me).
Podcasts We Loved This Week
- Andrea Merchak, Christopher Damman, & Tae Seok Moon. The bacteria and microbes in your gut can affect your body and mental health – engineering them promises new forms of treatment. Via The Conversation Weekly.
- Vivek Murthy: The Surgeon General warns about an epidemic of loneliness. Via Science Friday.
Products We Like
Owala FreeSip Insulated Stainless Steel Water Bottle
This is officially our new favorite water bottle. It is leakproof, keeps drinks cold for ~24 hours, is free of BPA and phthalates, and is super easy to disassemble and clean. Plus they have a ton of color options, including some fun colorways (I’m a fan of the 90s color block pictured above), or you can stick to simple black if you prefer.
humanOS Catalog Feature of the Week
This week, we’d like to highlight one of the courses from our Ideal Weight Program, developed by our good friend Stephan Guyenet. Simple food is exactly what it sounds like - food that is prepared and consumed as close as possible to its natural state, with limited added fats and sugars. These types of food enable you to stay satisfied and stave off hunger, while lowering energy density.
Notably, protein plays a key role in this approach.
In this course, Stephan breaks down the scientific rationale for the Simple Food Diet, what to eat, vital food preparation tips, and other information crucial to lasting success on this plan.
For more information, please refer to our How-to Guide for the Simple Food Diet, and the other materials from the Ideal Weight Program.