The brain senses macronutrient RATIOs, not just amounts


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The classic syllogism of “nutritionism” goes something like this:

  1. Eating food A makes people healthy.
  2. Food A contains nutrient X.
  3. Therefore we should isolate nutrient X, manufacture it in powder form, and ingest it large quantities to become healthy.

This seems pretty logical, and I certainly wouldn’t have questioned this basic mode of thinking a decade ago. And of course the approach has had many successes — taking vitamin C really does ward off scurvy if, for whatever reason, you’re subsisting on a diet devoid of vitamin C. But when we shift from “correcting deficiencies” to “enhancing health,” the approach seems to sputter, as people like Michael Pollan have argued.

The question, from my perspective, is: Why? Why do so many studies find that taking an isolated nutrient fails to reproduce the benefits observed from ingesting that nutrient in the context of a whole food (or, perhaps even more importantly, a whole meal or whole dietary pattern)? There are obviously many factors, such as the rate at which the nutrients are absorbed, and synergies between different nutrients in the food (a possible explanation for why nitrites are “good” when they from spinach and beets but “evil” in the context of fatty hot dogs).

A new study published last week in Neuron (press release here, abstract here) offers another clue. The study looked at the activation of “orexin/hypocretin” neurons in the hypothalamus, which “regulate energy balance, wakefulness, and reward.” It has long been known that glucose levels in the brain reduce the activation of these neurons. Researchers at the University of Cambridge tested how they responded to protein and fat, and found that certain amino acids increase the activation of the neurons, while fatty acids have no effect.

Okay, so the brain responds to macronutrient levels in the body. Cool. Carbs turn this particular neural signal up, and protein turns it down. And if you eat both protein and carbs at the same time, you’d expect that the net result will be the sum of the two signals. But that’s not what the researchers found. The combined protein-and-carb signal was a nonlinear combination of the two individual signals — meaning that these neurons were, in effect, responding to the protein-to-carb ratio rather than amounts. As the researchers put it:

In summary, our data show that the activity in the orx/hcrt system is regulated by macronutrient balance, rather than simply by the caloric content of the diet.

The bottom line: if you try to understand how this particular aspect of human physiology works by breaking food down into its constituent nutrients and testing them one by one, you’re doomed to failure because its response to individual nutrients is different from its response to combinations of nutrients. Which leads to a corollary: if you try to create a healthy diet by assembling a collection of pills and powders, you’re almost certainly sacrificing some of the synergies present in real foods.

5 Replies to “The brain senses macronutrient RATIOs, not just amounts”

  1. Very interesting, and by this logic it may seem that the foods we have learned to eat may be good combinations, one could also assume with pills and powders it would be possible, albeit possibly difficult, to find a combination more beneficial than what we get from a normal diet.

  2. My immediate thought: this appears to be evidence linking physiological response to a ratio of foods, in particular, the ratio of proteins abd carbs. Where else have we considered questions about the ratios between proteins and carbs? In the whole debate about high fat/high protein diets, such as the Atkins diet, vs. more traditional diets high in carbs. Could this evidence shed some light on the validity (or lack thereof) of high protein and fat diets?

  3. @Bruno: “Could this evidence shed some light on the validity (or lack thereof) of high protein and fat diets?”

    In principle, yes. In practice (at this point), I suspect not. For one thing, I should emphasize that this study doesn’t address the OVERALL response of the brain and body to macronutrient ratios — it just deals with one small input channel. The ratio that’s “optimal” for the “orexin/hypocretin” neurons may be totally different from the ratio that’s optimal for other mechanisms that the brain/body use to sense nutrient status. (In fact, that’s what we’d expect, since different input channels serve different purposes.)

    To me, the bigger point here isn’t that this research will tell us the optimal macronutrient ratio. It’s that any attempt to talk about the role of individual nutrients outside their broader dietary context is necessarily incomplete, because (as this study suggests) that’s not how the body works.

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