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Blood Glucose Levels Modulate Neural Control of Appetite

Anyone, who has ever experienced even a mild drop in blood glucose levels, understands the notion of hunger – a drive so powerful, that almost any food will taste good (energy-dense foods will taste even better!).

But whether or not elevated glucose levels can also suppress appetite is less well studied.

As study by Kathleen Page and colleagues from Yale University, just published in the Journal of Clinical Investigation, examines whether obese and nonobese individuals regulate their desire to consume high-calorie foods differently in response to changes in blood glucose levels.

Using functional MRI (fMRI) combined with a stepped hyperinsulinemic euglycemic-hypoglycemic clamp, that allows changing the blood glucose levels in a controlled fashion, the authors show that even modest reductions in blood glucose levels preferentially activate limbic-striatal brain regions in response to food cues to produce a greater desire for high-calorie foods.

In contrast, high-normal blood glucose levels preferentially activated the medial prefrontal cortex, an area of the brain involved in regulating impulse control and reducing motivation for rewarding stimuli such as food and drugs.

Interestingly, however, higher circulating glucose levels predicted greater medial prefrontal cortex activation only in lean but not in obese subjects.

As the authors discuss:

“These results are consistent with reports showing that high BMI is associated with decreased prefrontal activity at rest and after meal consumption and that obese subjects have an attenuated postprandial deactivation of the hypothalamus. These altered obesity-associated neural responses to food cues may contribute to overeating behavior, especially several hours after consumption of high-carbohydrate meals, a time when glucose often declines significantly below baseline levels.”

Thus, as the authors conclude:

“These findings demonstrate that circulating glucose modulates neural stimulatory and inhibitory control over food motivation and suggest that this glucose-linked restraining influence is lost in obesity.”

They also speculate that:

“Strategies that temper postprandial reductions in glucose levels might reduce the risk of overeating, particularly in environments inundated with visual cues of high-calorie foods.”

One strategy to avoid drops in blood glucose levels is not to allow yourself to go hungry by consuming smaller but more frequent meals. The other is perhaps to chose low-glycemic index foods in order to prevent the ‘crash-and-crave’ drive that follows rapid changes in blood glucose levels.

The study, certainly provides further evidence for important ‘biological’ differences between non-obese and obese people – while the former experience ‘natural’ appetite suppression with high-normal glucose levels, the
latter do not experience such a suppression of appetite and will need to resort to conscious restraint – a far more difficult undertaking.

Edmonton, Alberta

p.s. Hat tip to Bill Graber for pointing me to this study

Page KA, Seo D, Belfort-Deaguiar R, Lacadie C, Dzuira J, Naik S, Amarnath S, Constable RT, Sherwin RS, & Sinha R (2011). Circulating glucose levels modulate neural control of desire for high-calorie foods in humans. The Journal of clinical investigation, 121 (10), 4161-9 PMID: 21926468


  1. The other method of controlling blood glucose is low carb, and let our liver control the glucose from the low end of the range.

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  2. This is very interesting.

    However, I think it is important to note that in large studies, the impact of low GI foods on weight management has been minimal.

    Free full text here:

    Even though there was a statistically significant effect for low GI versus high GI on weight maintenance I’m not sure it as really clinically significant. Of course, there were more dropouts in the low protein-high GI group, but we can’t assume necessarily that these people were gaining weight (although it is possible) without any evidence of this.

    And despite the fact the we appear to be fixated on the idea of eating breakfast and frequent meals, the amount of research on various forms of fasting has been growning and it isn’t necessarily supporting the idea of greater meal frequency (or even breakfast consumption) for weight loss.


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  3. ” obese people … need to resort to conscious restraint …”
    That’s exactly true.

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  4. “using a stepped hyperinsulinemic euglycemic-hypoglycemic clamp” to control for sugar? — I’d be very interested to observe what was recorded about changes in insulin levels as well.

    It sounds like the study considers obesity to be a cause rather than a symptom. I’d be interested to see how a longitudinal study, say starting with several playschool children most of whom have yet to develop an outward appearance of obesity, fared over the years. I wonder if the same mechanism could be observed pre-obesity signs. And then I’d be interested to see if something happens in some children and not in others that turns on this mechanism via internal or external change (such as puberty, stop walking to school, start walking to school, diagnosis of various other allergies, etc. )

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  5. Isn’t that a post hoc, propter hoc conclusion – that a person has altered neural responses as a result of obesity? The participants with a higher BMI might also be obese *because* they have altered neural responses. No?

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