Summary

Cortisol is a steroid hormone produced by the adrenal glands that plays a key role in the body's response to stress. It helps regulate various bodily functions including metabolism, immune response, and the body's response to stress. 

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Introduction

The production of cortisol follows a diurnal rhythm - it's usually highest in the morning and decreases throughout the day. The production as well as secretion of cortisol is controlled by the body and can be influenced by our lifestyle, sleep, and other habits.

Cortisol helps the body respond to stress or danger, increasing heart rate, blood pressure, and glucose levels, ensuring the body has enough energy to handle the threat. However, prolonged exposure to high levels of cortisol due to chronic stress can lead to various health problems like weight gain, high blood pressure, disrupted sleep, reduced energy levels, and difficulty concentrating. 

Many factors, including physical and emotional stress, lack of sleep, poor diet, and lack of physical activity influence cortisol levels. Managing these factors through lifestyle changes can help maintain healthy cortisol levels and overall health.^[1,2,4]

There are also medical terms for describing diseases that are characterized by unusual cortisol levels, different from abnormalities caused by non-optimal stress and lifestyle habits. If there is excess cortisol in the body, it can cause Cushing disease. In contrast, if there is a state of insufficiency it can cause Addison disease. 

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Salivary Cortisol Testing

Salivary cortisol testing has emerged as a reliable and non-invasive method for assessing adrenal function. It allows the measurement of the biologically active fraction of cortisol in our bodies. Since cortisol levels follow a diurnal rhythm, multiple samples are taken throughout the day to capture this variation. The samples remain stable for multiple days when stored in room temperature, so remote testing is a viable option that is adopted in the Macromo Sleep and Stress test.^[1,7]

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Macromo Cortisol Reference Ranges 

In Macromo, the evaluation of cortisol levels is done in reference to the CIRCORT study^[11], which is specifically focused on ranges and changes in salivary cortisol throughout the day. By analyzing a diverse study population across 15 field studies, this research meta-dataset describes the distribution of cortisol levels in relation to age and sex, which you provide when registering the test kit.

The study chose percentiles as a statistical tool. The 5th percentile is utilized to determine the lower boundary of the reference range, below which only 5% of individuals fall. On the other hand, the 95th percentile indicates a threshold above which only 5% of participants are included.

If your results are not within the reference range or if you feel any symptoms, please, consult your health-care provider for more thorough examination.

There is also another approach to interpreting cortisol tests. You can find reference ranges used by laboratories, usually given in nmol/l units. However, reference ranges may vary between laboratories based on the procedures and equipment used. These are usually more forgiving when it comes to interpreting your cortisol levels for the purpose of determining how stressed you are, given that the lab reference ranges are mostly used as a diagnostic tool of various rare disorders.

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The Science Behind

Below you can dive into more in-depth information about the biochemistry of cortisol, its rhythm in our bodies, and the molecular mechanisms behind.

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The Biochemistry of Cortisol

Cortisol is synthesized from cholesterol in the zona fasciculata layer of the adrenal cortex. When the body experiences stress or low levels of blood glucocorticoids, the hypothalamus secretes CRH (corticotropin-releasing hormone). CRH then travels to the pituitary gland, where it stimulates the release of ACTH (adrenocorticotropic hormone) into the bloodstream. Once in the bloodstream, it reaches the adrenal glands and binds to receptors on the outer layer of the adrenal cortex, which triggers a series of biochemical reactions which culminate in the production of cortisol.

In the first step, an enzyme known as cholesterol desmolase converts cholesterol into pregnenolone. This takes place in the mitochondria of the adrenal cortex cells, and is often referred to as cholesterol side-chain cleavage. After that the conversion of pregnenolone to progesterone takes place. The following steps are a set of conversions catalyzed by several enzymes, transforming progesterone into cortisol.

Cortisol can exist in both active and inactive forms, which can be easily switched between. The inactive form is referred to as cortisone. The activation / inactivation path is mediated by enzymes:  11β-HSD1 and 11β-HSD2.

In the liver, cortisol undergoes metabolism. The enzyme 5α-reductase metabolizes cortisol, creating compounds like tetrahydrocortisol and tetrahydrocortisone. They are then coupled with other molecules in a process of conjugation. Conjugation makes metabolites more water-soluble, and therefore easier to remove from the body.^[2,3]

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The Diurnal Rhythm of Cortisol

Cortisol fluctuates on a daily cycle known as the circadian rhythm. Levels typically peak in the early morning providing a cortisol awakening response.^[4,8] Throughout the day, cortisol levels gradually decrease, reaching their lowest point around midnight. This decrease aids the body in preparing for sleep. This rhythm is guided by the light-dark cycles of our environment.

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Underlying Molecular Mechanisms

At the molecular level, the cortisol signal undergoes a series of interactions. It passes through the cell membrane and binds to glucocorticoid receptors present in the cytoplasm of the cell. This binding activates the receptor, leading to a change in its shape that enables it to transport cortisol into the cell's nucleus. Here, it interacts with the cell’s DNA and machinery, influencing the expression of specific genes, which in turn impacts a variety of cellular functions, such as immune response, metabolism, and inflammation control.^[5,6]

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Genetics 

Genetics plays a significant role in determining our cortisol responses. Specific genetic variations can affect how our bodies produce, utilize, and break down cortisol. For example, polymorphisms in the gene encoding the glucocorticoid receptor can alter the receptor’s sensitivity to cortisol. These genetic variations can influence individual responses to stress and susceptibility to conditions related to cortisol imbalance.^[5,6]

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Recommendations

Maintaining balanced cortisol levels is an important aspect of good health. The following options are supported by evidence and are also generally quite familiar to many people due to their simplicity and effectiveness.:

• Healthy lifestyle

Regular physical activity, a balanced diet, adequate sleep, and hydration are fundamental.

• Stress management

Techniques like meditation, deep-breathing exercises, and guided imagery can help manage stress levels.

• Limit caffeine

Excessive caffeine can disrupt your sleep cycle and increase cortisol levels.

• Maintain a regular sleep schedule

A regular sleep schedule aligns with your body's circadian rhythm, helping regulate cortisol production.

• An interesting effect of aromatherapy have been shown

Using lavender and rosemary scent has been shown in some studies to reduce serum cortisol levels and ease anxiety.^[9,10] 

• Laugh as a medicine

Laughter has been shown to reduce stress and the release of cortisol. It can be watching a funny movie or having a good time with your family and friends.^[12,13]

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The information and tests provided on our website are for educational purposes only and are not a substitute for professional medical advice. Always consult with your healthcare provider before making health decisions. Our tests do not diagnose or treat diseases. Individual results may vary and should be discussed with a healthcare provider.

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