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Human protein status modulates brain reward responses to food cues


Background: Protein is indispensable in the human diet, and its intake appears tightly regulated. The role of sensory attributes of foods in protein intake regulation is far from clear.

Objective: We investigated the effect of human protein status on neural responses to different food cues with the use of functional magnetic resonance imaging (fMRI). The food cues varied by taste category (sweet compared with savory) and protein content (low compared with high). In addition, food preferences and intakes were measured.

Design: We used a randomized crossover design whereby 23 healthy women [mean ± SD age: 22 ± 2 y; mean ± SD body mass index (in kg/m2): 22.5 ± 1.8] followed two 16-d fully controlled dietary interventions involving consumption of either a low-protein diet (0.6 g protein kg body weight−1  d−1, 7% of energy derived from protein, approximately half the normal protein intake) or a high-protein diet (2.2 g protein kg body weight−1  d−1, 25% of energy, approximately twice the normal intake). On the last day of the interventions, blood oxygen level–dependent (BOLD) responses to odor and visual food cues were measured by using fMRI. The 2 interventions were followed by a 1-d ad libitum phase, during which a large array of food items was available and preference and intake were measured.

Results: When exposed to food cues (relative to the control condition), the BOLD response was higher in reward-related areas (orbitofrontal cortex, striatum) in a low-protein state than in a high-protein state. Specifically, BOLD was higher in the inferior orbitofrontal cortex in response to savory food cues. In contrast, the protein content of the food cues did not modulate the BOLD response. A low protein state also increased preferences for savory food cues and increased protein intake in the ad libitum phase as compared with a high-protein state.

Conclusions: Protein status modulates brain responses in reward regions to savory food cues. These novel findings suggest that dietary protein status affects taste category preferences, which could play an important role in the regulation of protein intake in humans.


Alex’s notes: I’m pretty sure that protein is everyone’s favorite macronutrient. It receives an outstanding amount of attention from all corners of the health, nutrition, and fitness fields, and not just because you can’t beat a juicy steak. Protein intake is tightly regulated in animals and humans, and some have even proposed inadequate consumption of protein leads to obesity and related health consequences. After a protein deficit, when the protein status is low, food intake and food preferences show adaptive changes that suggest compensatory mechanisms aimed at restoring adequate protein status, and high-protein meals have been shown to elicit changes in brain chemistry compared to normal-protein meals. The study at hand aimed to further our understanding of the relationship between protein and its neural effects on food reward.

23 healthy, young women of normal weight followed two 16 day fully controlled dietary interventions involving consumption of individualized isoenergetic menus providing either a low-protein (LP) diet (0.6g / kg bodyweight; ~7% total calorie intake) or a high-protein (HP) diet (2.2g / kg bodyweight; ~25% total calorie intake). Each intervention was ended with a one-day all you can eat phase that offered a large array of foods and allowed the researchers to measure protein and energy intakes. Notably, because the total energy intake was kept constant the protein was exchanged for carbohydrates while fat and fiber remained identical in both groups. Additionally, whey protein isolate was added to certain foods to boost the protein content.

So what happened after just two weeks of protein underfeeding? There was greater stimulation of the brain for savory food cues. Savory foods are tasted through amino acid receptors, so a greater want for these foods is indicative of a brain in need of meat. Surprisingly, the brain didn’t respond differently than the HP group when presented images of high-protein foods, only savory foods. It is possible that changes in food preferences rely on existing learned associations between primary taste categories and macronutrient availability, which results in changes in taste preferences and leads to adaptations in protein intake. In other words, our ancestors didn’t have nutrient labels for food and instead associated the savory taste of meats with protein – which shows that taste is important for the regulation of protein intake in humans.

As for the HP group, they responded more too sweet food cues. The finding that both protein deprivation and overconsumption had a modulating effect is not really surprising since both can be damaging to the organism in the long-term. Both groups exemplified their food preferences during the buffet phase as the end of each intervention; the LP group consumed about 8% more protein, while the HP group consumed more carbohydrates. Interestingly, energy intake didn’t differ, suggesting that we regulate our protein intake by selecting foods of different nutrient content (as deemed by taste) instead of by changing the total food intake. We cannot rule out satiety, however, as protein is much more filling than other nutrients and this could be a reason for the equivalent food intake between groups.

Bottom line: Not too much, not too little, evolution wants us to have a protein status that is just right. Something I may try and recommend you do as well is to watch what you or others eat at the buffet next time you go. If you find yourself packing on the meat, you may need to rethink your overall diet. Then again, you could also just be a carnivore at heart – I know I am.


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