0:00 – Initial Rise of Cortisol in First 3 Weeks of a Low Carb Diet
3:30 – Cortisol Metabolism Alteration on Low Carb vs. Moderate Carb Diet
6:51 – Decreased Regeneration and Regeneration of Cortisol Due to Enzyme Activity
9:37 – Lack of Carbs Role in Glucocorticoid Metabolism Alteration
11:18 – Do You Need to Cut Carbohydrates to Lose Weight?
13:26 – Key Takeaways

Well, it’s well known that blood levels of cortisol, the stress hormone, increase during the first three weeks of keto. It’s not well known that cortisol metabolism at the tissue actually increases long term on the keto diet. In this video, I’m going to show you how cortisol metabolism at the tissue level changes on a keto diet and tell you what you can do to prevent this.

So to start, cortisol rises during the first three weeks on a ketogenic diet and is to aid in the production and sparing of glucose while ketone production ramps up. So I have a quote here from a paper titled Low Carbohydrate Diets and Men’s Cortisol and Testosterone, a Systematic Review and Meta Analysis.

And what they say is short term, less than three weeks, low versus high carbohydrate diets moderately increased resting cortisol, whereas long term, greater than or equal to three weeks, low carbohydrate diets had no consistent effect on resting cortisol. So basically, in the three week time frame when you first start a keto diet, you start to increase cortisol levels, which is a stress hormone.

We’re going to talk about why in just a second. But after that three week mark. The rise in cortisol is pretty inconsistent, so it’s not really clear that across all the studies that cortisol is elevated. So, why does cortisol elevate? Well, the researchers go on here to say, the increase in resting cortisol on short but not long term low carb diets is likely tied to the glucocorticoid’s role in glucose homeostasis.

They say cortisol, glucagon, and gluconeogenesis all increase on short but not long term low carb diets. As glucocorticoids increase gluconeogenesis, which is the production of glucose at the liver, the initial rise in cortisol may be partly responsible for a transient increase in gluconeogenesis on short term, low carb diets.

Additionally, cortisol may rise to spare glucose for brain function as the brain cannot significantly use fatty acids for fuel. Glucocorticoids inhibit glucose uptake and oxidation in adipose tissue and skeletal muscle, thereby conserving glucose for brain function. So essentially what happens is in the first three weeks of a ketogenic diet or a low carbohydrate diet, because you do not have the carbohydrates coming in, what winds up happening is you have to start up regulating these stress hormones, glucagon, cortisol, adrenaline, etc.

to liberate fatty acids and to also liberate glucose. from the stores from the tissues and also increase the production of glucose at the liver in a process called gluconeogenesis while inhibiting the use of glucose at tissues like the skeletal muscle and the fat tissue so that you can actually save that glucose for the central nervous system.

This happens essentially to until ketone production starts to ramp up effectively. So what they say here is is in contrast, endogenous ketone production increases sharply over the first three weeks of a very low carbohydrate diet and ketones can be used for the fuel by the brain. Thus, when ketones replace glucose for the majority of the brain’s fuel, cortisol’s glucose sparing effects are not needed and thus levels may return to baseline.

So basically, once the ketone production starts to ramp up within that three week time frame, Then the body doesn’t need as much gluconeogenesis because the central nervous system is, is partly running on ketones. Now, it can’t run entirely on ketones, so there’s still a decent amount of gluconeogenesis going on, but the, the ketones can take over a portion of the central nervous system’s need for carbohydrate or fuel needs in general.

The reason I’m bringing this up is because a lot, the rise in cortisol being limited to the first three weeks of a keto diet is Often referenced in the Keto sphere as a way to provide evidence that Keto isn’t actually stressful long term. Well, to counter that point, what we see here is we have a four week study comparing a high fat, low carb, and is essentially a ketogenic diet to a medium fat, medium carb diet in obese men.

And basically what the researchers found, and we’re going to get into the details, is that cortisol regeneration and cortisol degradation at the tissue level was actually higher on the high fat, low carbohydrate diet than on the medium fat, medium carbohydrate diet. So, even if serum cortisol levels aren’t higher on average, or the results are inconsistent, which is what we just saw in the meta analysis, the actual change of cortisol metabolism at the tissue level is shifted on the low carbohydrate diet, and what we’ll see And I’ll give you a hint here is it’s largely related to the lack of carbohydrates in the diet.

The paper here, just for anyone’s reference, is titled, Dietary Macronutrient Content Alters Cortisol Metabolism Independently of Bodyweight Changes in Obese Men. And so we have, we basically have a population of healthy men age 20 to 65 years old with a BMI of 30 to 40. So they were obese and then they were put on two different diets.

Um, there was two, actually two setups that were done, but the two different diets, one was a high fat, low carbohydrate diet, which had 5 percent carbs, which 22 grams of carbs per day. 66 percent fat, which is 128 grams of fat per day and 29 percent protein, which is 125 grams of protein per day. And then we also had a medium fat, medium carb diet, which was 34 percent carbs, which is 163 grams of carbs per day.

37 percent fat, which is a 77 grams of fat per day, and 29 percent protein, which was 137 grams of protein per day. And so, the high carb, uh, the high fat, low carb diet had very low carbohydrate intake. It had 5%, 22 grams of carbs per day compared to the medium fat, medium carbohydrate diet. The protein intake was roughly the same, and then the fat intake was adjusted between the different diets.

So, we can see that. Now, they did two different, two different studies with, with these men. One group was ad libitum, so they could eat as much as they want, but they had to adhere to these specific, uh, ratios, or these specific targets. And then on the other study, we had a controlled isocaloric feeding, where the men were fed 2, 000 calories a day.

Um, one was high fat, low carb, and one was medium fat, uh, medium carb. What they found in this study is that the men on the high fat, low carbohydrate diets had an increase In the regeneration of cortisol at the tissues through an enzyme called 11 beta HSD 1, and we’ll talk about that in just a second, and then the, and this was irrespective of weight loss in the diet, because in both groups, men lost weight, so whether they were on a medium fat, medium carb diet or the high fat, Low carb diet, they both lost weight, but the high fat, low carb diet actually increased regeneration, uh, or activation of cortisol at the tissues.

So the researchers here say, the increased 11 beta HSD1 activity on the high fat, low carb versus medium fat, medium carb diet was independent of differences in energy consumption and weight loss. The same effect was observed under fixed feeding, approximately isocaloric conditions. And the medium fat, medium carb diet induced substantial weight loss without altering the 11 beta HSD1 activity.

Moreover, the effect of the high fat, low carb diet was already apparent after one week of the diet when weight loss was minimal. So, it wasn’t about weight loss. It was about the carbohydrate content of the diet, and the lower the carbohydrate intake in the diet, so the high fat, low carb diet, saw an increased regeneration of cortisol by upregulating this enzyme, 11 beta HSD1.

So, I have a graphic here to show us. And so, What we see is we have cortisone on this left side, which is inactive cortisol, and then you have cortisol on this side, which is the active form of glucocorticoid cortisol, and you have the enzymes here, 11 beta HSD1 and 11 beta HSD2. 11 beta HSD2 takes cortisol and turns it into the inactive cortisone, 11 beta HSD1 takes cortisone and turns it into the active form of cortisol.

And so, basically, what we’re seeing is on the high fat, low carbohydrate diet, at the tissue level, we’re seeing increased activation of cortisone into cortisol, which just wouldn’t be an ideal thing because you’re increasing the amount of glucocorticoid, and typically, this is an indicator of stress. We can see that besides just increasing The activation of inactive cortisol from cortisone into the active form cortisol.

We also see that the degradation of cortisol, uh, by the, by other enzymes gets decreased. And these enzymes are five alpha and five beta reductase. This leads to not only a regeneration of cortisol from cortisone, but also a decreased breakdown of cortisol through these other enzymes. Five alpha and five beta reductase.

And so, the study here says, in obese men, a high fat, low carbohydrate diet increased whole body regeneration of cortisol by 11 beta HSD1, which we just talked about, and reduced the rate of inactivation of cortisol by 5 alpha and 5 beta reductases. So I have another graphic here from the study. And basically what we can see is you see the two different dietary setups.

So you have the ad libitum setup and you have the isocaloric setup where the calories were kept the same. And then the men here were allowed to eat as much as they desired. And basically what you can see in the black bars, you have the high fat, low carb diet, and in the, the white bars here, you have the medium fat, medium carb diet, and what we’re looking at.

is the rate of appearance of cortisol in these men. And so in the men on the high fat, low carb diet, we can see across all groups, ad libitum and isochloric, their cortisol levels or the rate of appearance of cortisol levels are higher. And then they gave them tagged cortisol. So basically, uh, a quarter of cortisol with a, uh, with the addition of a radioactive tracer on it so that they can see the metabolism of cortisol in the body.

And what they find is that even this, the men who were on the high fat, low carbohydrate diet had higher cortisol levels than the men on the or the higher rate of appearance of cortisol than men on the medium fat, medium carbohydrate diet. So this is showing at the tissue level that even if serum cortisol levels aren’t consistently elevated after keto, the overall metabolism is shifted towards active cortisol.

We have a decreased breakdown of cortisol and then the cortisone, which is the inactive form, actually gets converted more easily to cortisol because it up regulates the enzyme 11 beta HSD1 while down regulating the enzymes 5 alpha and 5 beta reductase. Now, the authors directly talk about in this paper that the lack of carbohydrates are the major drivers for the alterations in cortisol metabolism of the tissue.

They say, low carbohydrate intake appears to be the key factor responsible for alterations in glucocorticoid metabolism. Protein intake was similar between diets. Compared with baseline, fat intake was only marginally higher on the high fat, low carbohydrate diet, whereas carbohydrate intake was substantially lower.

So, essentially what we’re seeing is that on the high fat, low carbohydrate diet, the fat intake wasn’t that much higher than what the people were already doing. The major thing that they did was lower the carbohydrate intake overall. And they say, however, carbohydrate intake was also lower than baseline on the medium fat, medium carbohydrate diet, suggesting a threshold of reduced carbohydrate intake to mediate the effect.

So, even on the medium fat, medium carbohydrate diet, the researchers actually had to lower the carbohydrate intake to set these, uh, set these individuals up in this arm of the study. So, Even then they didn’t see the, the increases in cortisol they saw in the high fat, uh, low carb group. So they’re saying it’s, there seems to be a threshold effect where you start to raise cortisol with a lack of carbohydrates.

And then what they’re saying is this is supported by fasting insulin concentrations, which were decreased by the high fat, low carb, but not by the medium fat, medium carb diet in the ad libitum study, and might directly alter hepatic 11 beta HSD1 and 5 alpha and 5 beta reductase activities. So what they’re saying here is the lack of carbohydrates, are driving the change in these enzymes that increase the activation of cortisol while decreasing its breakdown and they’re, they’re hypothesizing that it may be related to insulin but they also talk in the paper there could be other mechanisms at play and I think there’s probably also other mechanisms at play.

The last piece here that’s really interesting to me from this paper. is that the men on the medium fat, medium carbohydrate diet actually lost similar amounts of fat mass without actually up regulating 11 beta HST1 activity and down regulating 5 alpha and 5 beta reductase. So, even though they lost body fat, even though they lost body weight, they didn’t actually drive the same stress response that the high fat, low carb diet actually did.

So, what they say here from the paper, they say in the ad libitum study, energy intakes were 154 kilocalories per day lower on the high fat, low carbohydrate diet than the medium fat, medium carbohydrate diet, and weight loss was correspondingly greater. In the isocaloric study, despite being served food of the same energy content, intake was slightly lower.

and weight loss greater on the high fat, low carbohydrate diet after corrections for unconsumed food. However, loss of fat mass was similar on the high fat, low carb, and the medium fat, medium carb diets in both studies. So, essentially, what they’re saying, and I guess one really important piece here, it’s a little nuanced detail, The men on the high fat, low carbohydrate diet, their appetites were lower, so they weren’t able to eat all the food.

So what you’re seeing is when they fed the men ad libitum, they automatically ate 154 calories less per day in the high fat, low carb group than the medium fat, medium carb group, which is, which basically led to the men losing a little bit more weight. So, and this is something we’ve talked about, Ethan and I talked about this directly on the podcast, that when you’re on the high fat, low carb diets, what happens is appetite gets knocked out, and then what winds up happening is you automatically tend to eat less on these diets, and you’re actually seeing that here in the study, and they were allowed to eat ad libinum as much as they wanted, and they were already 154 calories less than the group that had medium fat, medium carb.

The other thing is that, despite Being on a medium fat, medium carb diet, the, uh, calories were equated, both groups lost body fat and the body fat loss was similar between, between both groups. There wasn’t a significant difference. So, essentially, you can be on a medium fat, medium carb diet, not drive the cortisol metabolism such you’re increasing cortisol and still lose body fat, still, still lose body weight.

So, essentially, what are the key takeaways from these papers? First off, the high fat, low carb diets or keto diets are initially stressful during the first three weeks of the diet, as is seen with the rise in cortisol and other adaptive hormones. This is known, this is not, this is not contentious. So, in the first three weeks you go on a keto diet, there’s going to be stress, and it’s likely driven by the lack of carbohydrate, as the body has to shift over metabolism, because it doesn’t have carbohydrate coming in, and the brain still needs fuel in the form of carbohydrate until ketone production can start to really ramp up.

The other thing is, after the three week mark, Even though the rise in serum cortisol is inconsistent, it appears that the tissues still shift towards up regulating cortisol metabolism, which still would indicate that there’s a degree of stress being recognized by the body due to the lack of carbohydrate.

Now, the next thing is, you can lose weight on a medium fat, medium carbohydrate diet. It’s not necessary to go to a high fat, low carb diet to lose weight. In this study, they had took obese men and even on a medium fat, medium carb diet, they still lost weight altogether. And the weight loss was relatively comparable when the researchers accounted for the decreased appetite in the high fat, low carb group.

So, given this, if you are looking to lose body fat without driving stress, And if you also want to improve your metabolic function, you don’t have to go on a high fat, low carb diet to do this. You can go on a medium fat, medium carbohydrate diet and still lose appreciable amounts of body fat if the diet is set up appropriately.

And I do cover how to do this in more depth in the video and podcast that will link at the end of this video. And also, if you’re looking for personalized step by step guidance on how to lose weight without driving stress, you can check out my new coaching program linked in the description below.