You've heard the story before: when you eat carbohydrate-rich foods that digest quickly, it sends your blood sugar and insulin levels soaring, then your blood sugar level comes crashing back down and you feel hungry and cranky. You reach for more carbohydrate, perpetuating the cycle of crashes, overeating, and fat gain.
It sounds pretty reasonable-- in fact, so reasonable that it's commonly stated as fact in popular media and in casual conversation. This idea is so deeply ingrained in the popular psyche that people often say "I have low blood sugar" instead of "I'm hungry" or "I'm tired". But this hypothesis has a big problem: despite extensive research, it hasn't been clearly supported. I've written about this issue before (1).
A new study offers a straightforward test of the hypothesis, and once again finds it lacking.
The study
Bernd Schultes and colleagues used a clever design to isolate the effect of blood glucose on appetite (2). They recruited 15 healthy young men, and on two occasions fed them an identical light breakfast.
On one occasion, they waited one hour after the meal and infused saline containing 50 grams of glucose into the volunteers' bloodstream over a one-hour period. On the other occasion, they did the same thing except using saline without glucose. Throughout the infusion, and one hour afterward, the researchers monitored levels of blood glucose, blood insulin, and markers of appetite.
The results
As expected, the glucose infusion markedly increased blood glucose and insulin levels in the hour following the meal. After the researchers stopped the glucose infusion, the volunteers' blood glucose levels declined, eventually reaching a level significantly lower than the control condition (54 mg/dL vs 70 mg/dL). This is the post-meal "crash" that is supposed to trigger appetite.
Yet levels of hunger, appetite, satiety, and fullness didn't differ between groups at any time-- either during the infusion or afterward.
Discussion
We have extensive evidence that the brain pays attention to blood glucose levels, and triggers appetite when it goes too low as part of a suite of protective responses to maintain blood glucose level (this is called the "counterregulatory response"). However, the evidence overall suggests that you have to have pretty serious hypoglycemia for this to happen-- something that rarely occurs in people who aren't using insulin to treat diabetes. When researchers actually measure the blood glucose level of non-diabetic people who report feeling "hypoglycemic", a small percentage of them really are hypoglycemic, but the vast majority have perfectly normal blood glucose levels (3, 4, 5, 6). Hypoglycemia is not something that occurs frequently in the general non-diabetic population, and it doesn't offer a compelling explanation for why we feel hungry or tired between meals.
The brain listens to a variety of signals that indicate the body's energy status, and it integrates these signals to determine your sensation of hunger or satiety (7). Glucose is one of the signals the brain listens to, but there are many others, and the brain doesn't appear to pay very much attention to the glucose signal when it's within the range that occurs in the daily life of most people. In contrast, the brain pays attention to levels of leptin, CCK, GLP-1, glucagon, amylin, ghrelin, and signals ascending from the gut via the vagus nerve (7).
I like this study because it manipulated blood glucose levels in a way that's not likely to be confounded by variables that bedevil other study designs. They pulled this off by directly manipulating blood glucose, mimicking the glucose profile of a high-glycemic meal to see if post-meal fluctuations at the extreme end of the normal range affect appetite.
And, consistent with most previous research, it looks like they don't. How do we reconcile this with the fact that some single-meal studies have found that lower-glycemic meals are more sating than higher-glycemic meals (8)? Here's what I think. The sating effect of low-glycemic meals probably doesn't have much to do with blood glucose at all, but rather: 1) the fact that these studies are usually not properly controlled for other variables known to affect satiety, such as calorie density, fiber, protein, and palatability; and 2) the fact that lower-glycemic foods digest more slowly and therefore tend to leave carbohydrate hanging around in the gut interacting with intestinal satiety receptors for longer.
The authors conclude:
These findings clearly speak against the notion that fluctuations in glycemia and also insulinemia represent major signals in the short-term regulation of hunger and satiety.
Bariatric MD Arya Sharma also had some good thoughts on this study (9):
The lesson here, I guess is that, just because there is a seemingly compelling narrative to support an idea, it does not mean that that’s how biology in real life actually works.
I agree!
