Eating Licorice May Alter Results of Salivary Cortisol Tests: Study

Researchers say cortisone may be more robust biomarker as levels less variable

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Eating licorice can increase the amount of cortisol detected in saliva, but licorice consumption does not alter salivary levels of a cortisol metabolite called cortisone, a recent study has found.

Cortisone also is less variable in response to other confounding variables, and researchers proposed salivary cortisone may be a more robust biomarker for Cushing’s syndrome than salivary cortisol.

The study, “Confounding effects of liquorice, hydrocortisone, and blood contamination on salivary cortisol but not cortisone,” was published in the journal Endocrine Connections.

Measuring levels of cortisol in saliva is a common tool used in the diagnosis of Cushing’s syndrome, which is characterized by elevated levels of the stress hormone.

In this study, researchers examined several potential confounding variables,  external factors that may reduce the reliability of these tests.

In the first part of the study, 30 healthy adults  were given a daily supplement of licorice at one of three doses for six weeks. Four of the original 30 participants were excluded from the study. Licorice contains a compound called glycyrrhizic acid that when ingested may reduce the conversion of cortisol into cortisone.

Researchers noted the middle dose used in the study would correspond to a 65–70 kilogram (around 150 pounds) person eating about 100 grams (3.5 ounces) of confectionary licorice per day.

Results showed salivary cortisol levels increased significantly for participants on the two higher doses of licorice — at the highest dose, the average level was nearly doubled. Cortisol levels remained high until about four days after licorice supplementation was stopped, and similar results were seen in both male and female participants.

In contrast, levels of salivary cortisone were not significantly altered by any of the licorice doses.

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Studies with hydrocortisone cream, blood as sample contaminants

In a separate set of experiments, participants were asked to apply a hydrocortisone cream to their hand using their fingers and collect saliva before and after. Over-the-counter hydrocortisone creams are commonly used to ease itching; their active ingredient works by mimicking the activity of cortisol.

Results showed after applying the cream, salivary cortisol levels increased by more than 1,000 times. No changes in cortisone or cortisol levels were seen if participants wore a nitrile glove on their cream-contaminated hand.

In a final set of experiments, researchers collected saliva and blood samples from participants, and these were mixed together to simulate small amounts of blood contaminating a saliva sample (for example, from a small cut in the mouth).

Results showed cortisol levels were significantly elevated when blood contamination was at least 0.5%. Samples with this extent of blood contamination could almost always be identified visually, the researchers noted.

“Salivary cortisol may be falsely elevated by liquorice, blood in saliva, and topical hydrocortisone. These confounders may be minimized by refraining from liquorice consumption for 1 week before sample collection, avoid handling sampling equipment with bare hands, and rejecting samples with a visible pink tint,” the researchers wrote.

In contrast to the results with cortisol, neither licorice supplementation nor blood contamination led to a significant change in saliva cortisone levels. Hydrocortisone cream contamination led to a statistically significant increase in saliva cortisone levels, but the magnitude was much smaller than that of cortisol (32%, as opposed to an increase of more than 1,000 times).

“An important finding is that concentrations of salivary cortisone were not affected by either liquorice intake or blood contamination and only marginally affected by topical hydrocortisone contamination,” the researchers wrote.

While they noted that further work is needed to validate the results of this small study and confirm if the same findings hold true in people with Cushing’s, the team proposed measuring salivary cortisone could be more useful than salivary cortisol to screen for Cushing’s.

“Salivary cortisone … has a high diagnostic accuracy for [Cushing’s syndrome] and is essentially unaffected by the aforementioned preanalytical confounders and may thus be considered a more robust screening instrument for [Cushing’s syndrome] than salivary cortisol,” they wrote.