How Does a Ketogenic Diet Affect YOU? Part 2: A Deep Look Into Cortisol

by Katie Mark

Recent high hopes for high-fat diets have us further evaluating the ketogenic diet for a wider population. In this three-part series, we’re examining how the ketogenic diet affects biomarkers. Part 1 of this series investigated what ketosis does for fasting glucose and insulin. In Part 2, we look at how a ketogenic diet may affect cortisol levels.

High-fat…high cortisol…high stress?

Cortisol is considered the “stress hormone,” and it influences blood sugar levels, blood pressure, immune response, and stress response. Chronically elevated levels of circulating cortisol can hinder cognitive performance, disrupt sleep, impede immune function, increase abdominal fat, and cause blood sugar imbalances.

Studies have found that cortisol levels increase on a ketogenic diet, but some say the relationship between ketosis and high cortisol needs to be made clearer. First, chronically elevated cortisol correlates with metabolic syndrome, a group of symptoms such as high blood sugar, excess abdominal fat, and abnormal cholesterol levels that increase the risk for diabetes, heart disease, and cancer.

It seems possible that ketogenic diets may cause metabolic syndrome because higher cortisol levels suggest the onset of metabolic syndrome. However, this isn’t the whole picture: It’s also possible that there are multiple forms of cortisol, and their measurements mean different things.

Cortisol is measured in bodily fluids, including urine, saliva, and blood. Multiple forms of cortisol are measured from these samples: cortisone (the inactive form), free cortisol (the active form), and metabolites of cortisone and cortisol resulting from enzyme activity. Equally important, these levels of cortisol biomarkers can vary depending on the time of day.

A holistic understanding of cortisol metabolism relies on looking at the enzymes 11β-hydroxysteroid dehydrogenase (11β-HSD) and 11β-HSD1 (a subtype of 11β-HSD). 11β-HSD1 is found in every cell, but the highest amounts are found deep within fat cells. In fact, it does not matter if a person’s blood cortisol level is low, medium, or high because a highly active 11β-HSD1 will generate a high amount of cortisol inside cells.

Here is a breakdown of cortisol metabolism:

  • Production: 11β-HSD converts cortisol (active) to cortisone (inactive)
  • Regeneration: 11β-HSD1 converts cortisone to cortisol
  • Clearance: Other enzymes help metabolize cortisone and cortisol into metabolites

The cortisol profile of metabolic syndrome, which the ketogenic diet reverses, consists of:

  • High cortisol production
  • High cortisol clearance rates
  • High 11β-HSD1 expression in adipocytes and low 11β-HSD1 expression in the liver (the location that determines where and when cortisol is regenerated)

Now, let’s see how a 24-hour urine proxy is used for detecting cortisol. This proxy results in a less-than-clear picture because cortisol levels are affected by production, regeneration, and clearance. For instance, if clearance decreased or if regeneration increased, cortisol levels could go up if production stayed the same or lowered. This is analogous to simply measuring someone’s total cholesterol without observing LDL and HDL.

Take home message: levels may appear similar when there is a big difference in cortisol metabolism.

One study, published in The Journal of Clinical Endocrinology and Metabolism, used 17 obese men and randomly assigned them to an ad libitum (eat as much as you want) high fat-low carbohydrate (HF-LC) diet (66% fat, 4% carbohydrate) or moderate fat-moderate carbohydrate (MF-MC) diet (35% fat, 35% carbohydrate) for four weeks.

The study found a reversal of the previously described metabolic syndrome cortisol profile for only the HF-LC group: blood cortisol increased, clearance decreased and regeneration increased (due to an increase in 11β-HSD1 activity in the liver). According to the researchers, the ketogenic diet improved the cortisol profile because it was different from the cortisol profile seen in metabolic syndrome.

Furthermore, even though the MF-MC group lost a similar amount of weight, there was no change in 11β-HSD1 activity. This increase in 11β-HSD1 activity in the HF-LC group was independent of the differences in energy intake and weight loss because the same effect was seen in the controls.

A final component to note is that obesity is associated with high cortisol. However, the connection between obesity and elevated serum levels of cortisol has not always been a consistent connection.

Some people with high stress and lots of abdominal fat had normal or low levels of cortisol in their blood. Usually, chronically elevated levels of cortisol leads to increased adiposity; yet, there have been cases of people with high stress and high cortisol, but no obesity. And as we saw in “The Basics of the Ketogenic Diet,” the ketogenic diet has demonstrated effectiveness as a weight loss tool.

What’s the verdict?

We see that diet, especially a carbohydrate-restricted one such as the ketogenic diet, may increase certain forms of cortisol. But blood cortisol levels are only half the story—cortisol levels inside cells illustrate the other half. Also, cortisol will vary depending on the time of day, with levels highest in the morning. Caffeine, stress, and exercise can also increase cortisol levels.

Ultimately, further research is needed to better understand the connections as to why cortisol increases on a ketogenic diet and if cortisol levels are more affected by other variables, such as the activity of the 11β-HSD1 enzyme.

Katie Mark is a first year Nutrition Communication student from Miami, Florida. Due to Boston’s Snowpocalypse, she does not foresee herself living in Boston in the future, so she will return to South Beach following graduation.

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