Wednesday, June 2, 2010

Cortisol response to stress is much more elevated with ingestion of glucose than with protein or fat

Cortisol is a hormone that does a number of different things; a jack of all trades among hormones, so to speak. It tells the liver to produce glucose, preventing hypoglycemia. It also tells the liver to synthesize glycogen, which is in some ways the opposite of producing glucose. It tells the stomach to secret gastric acid. It is an anti-diuretic hormone. It suppresses the immune system, which is why it is frequently used to reduce inflammation, and treat allergies and various autoimmune diseases. It jump-starts an increase in free fatty acids in circulation, thus helping provide an important source of energy for endurance exercise.

Cortisol, together with epinephrine (a.k.a. adrenaline), even contributes to the creation of surprise-induced memories. It is because of this action of cortisol that Americans reading this post, especially those who lived in the East Coast in 2001, remember vividly where they were, what they were doing, and who they were with, when they first heard about the September 11, 2001 Attacks. I was living in Philadelphia at the time, and I remember those details very vividly, even though the Attacks happened almost 10 years ago. That is one of the fascinating things that cortisol does; it instantaneously turns short-term contextual memories temporally associated with a surprise event (i.e., a few minutes before and after the event) into long-term memories.

Similarly to insulin, you don’t want cortisol levels to be more elevated than they should naturally be. Natural levels being those experienced by our hominid ancestors on a regular basis. You need cortisol, but you don’t need too much of it. Many tissues in the body become resistant to hormones that are more elevated than they should be, like insulin and leptin, and this is also true for cortisol. It is a bit like people constantly shouting in your ears; after a while you cover your ears, or they get damaged, so people have to shout louder. If you frequently have acute elevations of cortisol levels, they may become chronically elevated due to cortisol resistance.

Chronically elevated cortisol levels are associated with the metabolic syndrome, the hallmark of the degenerative diseases of civilization.

Stress causes elevated cortisol levels. And those levels are significantly elevated if you consume foods that lead to a high blood glucose response after a meal. That is what an interesting experimental study by Gonzalez-Bono and colleagues (2002) suggests. The full reference and link to the study are at the end of this post. They used glucose, but we can reasonably conclude based on glucose metabolism research that foods rich in refined carbohydrates and sugars would have a very similar effect. If we think about the typical American breakfast, possibly even a stronger effect.

In order to do their study they needed to put the participants under stress. To cause stress the researchers did what many college professors have their students do at the end of the semester, which is also something that trial lawyers and preachers are good at, and something that most people hate doing. You guessed it. The researchers had their subjects do, essentially, some public speaking. The experimental task they used was a variation of the “Trier Social Stress Test” (TSST). The researchers asked the participants to conduct a 5-minute speech task and a 5-minute mental arithmetic task in front of an audience.

The participants were 37 healthy men who fasted for at least 8 h prior to the study. They were randomly assigned to one of four groups. The glucose group consumed 75 g of glucose dissolved in water. The fat group consumed 200 g of avocado. The protein group drank 83 g of proteins dissolved in water. The fourth group, the water group, drank plain water.

From a real world perspective, the fat and protein groups, unlike the glucose group, were arguably overloaded with their respective nutrients. Many people would not normally consume that much fat or protein in one single meal. This makes the results even more interesting, because it seems that fat and protein lead to virtually the same response as water, regardless of the amount ingested. The table below shows the cortisol responses for all groups.

As you can see, the cortisol response for the glucose group is a lot more elevated. How much more elevated? In the inner square at the top-left part of the figure you have the areas under the curve (AUC), which are essentially the estimates of the integrals of the cortisol curves for each of the groups. Usually AUC is a key measure when one looks at the potential negative impact of the elevated levels of a substance in the blood. Note that the cortisol AUC for the glucose group is much larger, about two times larger, than the cortisol AUCs for the other groups.

When one has a morning car commute, what is going to happen? Typically cortisol levels will be elevated, unless the commute is uneventful and done completely on “automatic pilot”; which is not very common, as people cut off in front of each other, make irritating mistakes etc.

What if, before that commute, one eats a “solid” breakfast with plenty of “healthy” sugary cereal covered with honey, a glass of “healthy” low-fat milk (of course, because fat “raises bad cholesterol”), and maybe three pancakes covered with syrup?

Cortisol levels will be much more elevated.

Doing this often, maybe after several years a person will become eligible for death by sudden cardiac arrest while doing some light activity.


Gonzalez-Bono, E., Rohleder, N., Hellhammer, D.H., Salvador, A., & Kirschbaum, C. (2002). Glucose but Not Protein or Fat Load Amplifies the Cortisol Response to Psychosocial Stress. Hormones and Behavior, 41(3), 328–333.


LeonRover said...
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LeonRover said...

I see from the abstract that stimulation of the sympathetic side of the HPA axis is the focus of the study. This is an unsurprising result for glucose, since it is well known that that a GTT Glucose load (75 gm)will have invoked an insulin response 45 minutes after administration of Glucose drink.

Insulin is the hormone which modulates the parasympathetic response of the HPA axis. Thus one should expect more cortisol would be pumped in to overcome the raised insulin. In fact I am a little surprised that the scientists chose not to measure insulin levels.

John said...

This is pretty cool. Where does the idea that [longterm] low carb/ketogenic diets lead to chronically higher cortisol fit in?

What if the "meals" were given directly after the public speaking? I wonder if each nutrient's effect on cortisol would parallel the above study...

Ned Kock said...

Hi Leon.

Yes, sometimes researchers go looking for something, find something else, and write about that something else.

I agree about the insulin; it would have been good to have it on a graph.

Note that water leads to a zero insulin response. Protein, on the other hand, leads to a non- trivial insulin response (see link below), which is admittedly complex and involves other hormones.

Yet the cortisol response in the water, protein and fat groups was essentially the same. And it was much lower than the cortisol response in the glucose group. So, insulin, in this context, might not have played much of a role.

Ned Kock said...

Hi John.

Cortisol levels seem to be higher in ketogenic diets, because cortisol also plays a role in fat burning. In ketogenic diets circulating FFAs are higher, as muscles use them for energy. However, stress-related elevations are not as high as they are with high glucose levels, and the hormonal mix is overall more favorable. This seems to be, among other things, what these folks found:

In ketogenic diets, insulin levels are reduced, and growth hormone levels are increased. Related to Leon’s comment above, often the whole hormonal mix matters more than what is happening with each individual hormone.

I would be interested in seeing the response to a highly glycemic meal after the stress task. I think blood glucose would go up higher in the glucose group (in this study it peaked at around 160 mg/dl, versus virtually nothing for the other groups), because the stress response leads to elevated FFAs and mild temporary insulin resistance. This would be a bad outcome, but from a different angle.

LeonRover said...

Hi Ned

I don't read the graphs like that. I see protein and water having the same cortisol response (about 22), fat gives a a response 20% above that (27), while the glucose response at 50 being over 250% of water and protein.

I checked out Holt's Insulin Index Study. It was interesting that 1000 kJ represents the calorific intake of a snack. Except for fish, the Protein Rich Foods are mixtures of Fat and Protein and Carbohydrate, but the only item to have a comparable Insulin AUC to Bread was baked beans.

It would have been nice if the study had used the protocol which is usual in pharmaco-kinetic studies and reported the Glucose max, Insulin max and the Times to reach these maximum values.

It seems to me however, that the Holt Study is in agreement the Cortisol Study that Fat induces more of an insulin response than protein and hence that extra cortisol (above the base response of water and protein) is needed to damp down the insulin mediated parasympathetic response.

Ned Kock said...

Indeed, the cortisol response for the fat group is a bit higher, but then again these folks ate a ton of avocado (200 g!), which is not exactly pure fat.

I would expect the insulin response to pure fat (or something like cream) to be zero. The insulin response to something like butter, however, would not be zero because butter has some protein in it.

Ned Kock said...

200 g of avocado will have about 4 g of net carbs (20 g total; 16 g fiber), and 5 g of protein.

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