How to Balance Melatonin and Cortisol Levels

The 'Stress in America' poll by the American Psychological Association for 2022 revealed some very worrying statistics. Over 80% of our nation reports experiencing high stress due to current world events and financial issues.

The interplay between stress and sleep is scientifically linked. When we are stressed and not well-rested, our bodies and brain suffer. With all this trepidation, it's no wonder about one-third of adults in America are getting less than the recommended seven hours of sleep.

This article will highlight the hormone responsible for keeping us on high alert (cortisol) and the one that assists us in slumber (melatonin). We will look at how the two interact, what occurs with imbalances in either or both, and how to support their optimal levels in functional medicine style.

Beyond the benefits of balancing our sleep-wake cycle, these two players have system-wide effects and their interplays that are quite extraordinary. You won't want to miss this. Let's dive in.

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What is Melatonin?

Melatonin (N-acetyl-5-methoxytryptamine) is both a hormone and an antioxidant. It is classified within the indolamine family of neurotransmitters, with serotonin, and synthesized from tryptophan. It is produced in humans, plants, and microbes and found in various dietary sources. (1-2)

Melatonin is mainly known for its ability to regulate the sleep-wake cycle (circadian rhythm or chronobiology) via its release from the pineal gland. Yet it is also produced in other cells. For example, the enterochromaffin cells in the gut produce 400 times more melatonin than the pineal gland. Other cells that produce melatonin include bone marrow cells, lymphocytes (white blood cells), mast cells (immune cells), and epithelial (skin) cells. (1-4)

Furthermore, melatonin receptors are found throughout the whole body, including the brain, cardiovascular system, eyes (retina), liver, kidney, breasts, reproductive organs, fat cells, adrenal glands, pancreas, spleen, and placenta. It is also present in nearly all bodily fluids. This indicates that melatonin's role in the body is much more vast than the potent influence our circadian rhythm has on our health. (1-2, 4)

Outside of chronobiology, melatonin also plays a role in protecting cells and tissues from oxidative stress that can damage them, acting as an antioxidant. It is also involved with multiple activities that include mitochondrial homeostasis, gene regulation, modulation of inflammatory pathways, immune signaling cascades, gut, and digestive health, and many additional regulatory pathways. (1-5)

Aging, illness, diet, environmental factors, bright light at night from cell phones, computers, fluorescent/LED light, medications, and lifestyle (shift work), all impact melatonin secretion.

How Does Melatonin Work?

Light exposure is received through the retina, and this information is transmitted to the pineal gland regulating its secretion of melatonin. Therefore, light exposure (sunlight and artificial) is the primary regulator of melatonin and is based on a daily pattern.

Melatonin is also produced with light exposure concurrently with vitamin D. It is believed to act as an antioxidant to protect the skin from sun damage.

Whereas vitamin D may be referred to as the "sunshine vitamin," melatonin is often referred to as the "hormone of darkness." This is because it is produced in the darkness and decreases with light exposure. Connections between the two represent almost a yin and yang, with vitamin D deficiency suggesting a "sunlight deficiency" and melatonin as a "darkness deficiency."

What is Cortisol?

Cortisol is a steroid hormone that is synthesized from cholesterol. It is the primary glucocorticoid produced in the adrenal glands in the zona fasciculata layer in response to a physical or psychological stressor. As a result, it is known as "the stress hormone."

Glucocorticoid receptors are present in most body tissues. This means cortisol can affect nearly every organ system, including the following:

• Nervous
• Immune (Cortisol leads to the breakdown of proinflammatory T cells, suppression of B cell antibody production, and reduction of neutrophil migration during inflammation.)  
• Cardiovascular
• Respiratory
• Endocrine (Reproduction and Hormonal Levels)
• Musculoskeletal
• Integumentary (Skin)
  

Cortisol has several physiologic effects, allowing the brain and body to respond and protect us from stress. This means shutting down "rest and digest" functions and upregulating "fight, flee, or freeze" responses, such as (6-8):

• Adjusting breathing rate and muscle tone
• Down-regulating gut and reproductive functions
• Raising blood glucose level
• Increasing fat breakdown (catabolic)
• Increasing heart rate
• Increasing blood pressure
• Lowering inflammation
• Increasing alertness

How Does Cortisol Work?

Although cholesterol can be obtained in the diet, it is also made in the liver. It follows several pathways in the adrenal glands to be converted into cortisol.

The hypothalamus-pituitary-adrenal (HPA) axis regulates cortisol production and secretion. (6-8) First, stress activates the parvocellular nuclei (PVN) in the hypothalamus gland. Following this activation is a release of corticotrophin-releasing hormone (CRH), which is mediated by norepinephrine, serotonin, and acetylcholine levels.

CRH then stimulates the release of Adrenocorticotropic hormone (ACTH) from the anterior pituitary. ACTH acts to increase Low-Density Lipoprotein (LDL) cholesterol receptors to increase the activity of cholesterol desmolase. This enzyme is the rate-limiting step to cortisol synthesis and converts cholesterol to pregnenolone, a precursor to cortisol. Once ACTH is released, it reaches the adrenal cortex. There it binds to the melanocyte type-2 receptor (MC2R) on cells and stimulates cortisol release into the bloodstream.

The majority of glucocorticoids circulate throughout our body in an inactive form, either bound to corticosteroid-binding globulin (CBG) or albumin. The inactive form is activated in most tissues by 11-beta-hydroxysteroid dehydrogenase 1 (11-beta-HSD1). 11-beta-HSD2 inactivates cortisol back to cortisone in the kidney and pancreas to balance levels.

Once sufficient cortisol is released, a negative feedback loop ensues. Specifically, cortisol levels inhibit the release of both ACTH and CRH, lowering the production of cortisol. (6-8)

What is The Relationship Between Melatonin and Cortisol?

The HPA axis follows a circadian rhythm, with cortisol and melatonin on opposing ends of the day-wake cycle.

In general, cortisol levels in the blood are highest in the early morning (around 8 a.m.) and decrease slightly in the evening and during the early sleep phase. (6-8)

Melatonin secretion begins after sunset, peaks overnight between 2 a.m. and 4 a.m., and gradually decreases during the rest of the night. Blood levels of melatonin are generally low during the day.

This pattern helps to regulate an individual's daily sleep-wake cycle, known as the circadian rhythm. Interestingly, whereas melatonin tends to have more metabolic "boosting" activities, cortisol is more catabolic.

They can be thought of as "yin and yang" hormones, balancing each other.

Effects of an Unbalanced Relationship Between Melatonin and Cortisol

Cortisol and melatonin are usually in sync based on one's circadian rhythm. Cortisol peaks in the morning to wake us, and melatonin rises at night to help us enter slumberland.

Circadian imbalances from dysregulated cortisol and melatonin can lead to daytime sleepiness and brain processing issues such as decreased alertness and problems with memory and decision-making.

When there is a constant rise in cortisol, our natural rhythm is disturbed. Besides not getting all the physical and hormonal regulation benefits of sleep, we also lose out on the many benefits of melatonin, such as antioxidant support, immune modulation, and gut-healing properties. This is why you will hear, "high-stress levels cause inflammation and lower immunity."

Functional Medicine Labs to Test for Melatonin and Cortisol

Clinicians often assess sleep and stress levels with a full health history and symptom questionnaires. They may also wish to measure markers of melatonin and cortisol to determine imbalances and evaluate the next course of treatment.

• A melatonin profile that tests melatonin levels in the morning, afternoon, and evening can provide a snapshot of the influence of this hormone on the sleep/wake cycle.
  

• A Rhythm + CAR (Cortisol Awakening Response) Test includes an Adrenocortex Stress Profile, the Cortisol Awakening Response, and the Comprehensive Melatonin Profile for complete hormone analysis.
  

• The CAR Profile uses a six-point saliva collection to analyze cortisol patterns and assesses adrenal hormone/HPA axis dysfunction.
  

How to Balance Melatonin Naturally

Melatonin

If melatonin is found to be low, endogenous sources can be taken in through the diet via many plant and animal foods that are high in its content. Due to its biological conversion to melatonin, tryptophan-rich foods can also be eaten. However, for some individuals, the conversion from tryptophan to serotonin and, ultimately, to melatonin may not be efficient due to genetic variations in the enzymes involved in their conversion.

Studies have shown that plant sources of melatonin have increased overall systemic antioxidant status and elevations in melatonin. In one study with twelve healthy men, drinking one kilogram of orange or pineapple juice or ingesting two whole bananas resulted in a significant rise in serum melatonin and increased antioxidant status (as measured using the FRAP and ORAC analyses).

Various vegetables, fruits, nuts, seeds, grains, oils, and spices contain melatonin. Tart cherries are one of the most abundant sources. In one study, Montmorency cherries were reported to contain 13.46 ± 1.1 ng of melatonin per gram of cherries, equating to 50 lbs. of cherries to reach the physiological dose of 0.3 mg melatonin.

For this reason, many may choose to supplement melatonin. Physiological dosage of .3mg has had comparative results regarding sleep outcomes as higher doses.

Vitamin B12

A few human clinical trials suggested that vitamin B12 supplementation increased the phase advance effect of morning light and decreased nocturnal melatonin levels, specifically in the form of methylcobalamin. This may lead to better sleep.

Blue-Light-Blocking Glasses

Light, particularly blue light, suppresses the circadian release of melatonin. Various studies have reported that Blue-light-blocking glasses can protect from the melatonin-suppressing effects of light. In one study, when participants wore blue light-blocking glasses during a 60 min light pulse at 0100 h, there was a slight increase in melatonin versus a significant decrease in controls. The benefits of these glasses have also been found in those with insomnia, Delayed Sleep-Wake Phase, and in improving subjective reports in healthy adults without sleep or circadian disorders.

A Comprehensive Clinical Approach to Melatonin

Assessing genetics, triggers in alterations in melatonin (e.g., increased inflammation, toxic exposures, and stressful events), and evaluation of lifestyle factors such as sleep habits, physical activity, diet, and stress, are all important to address the root cause of melatonin imbalances. Modifying one's response with meditation, breathwork, creative arts, and support systems can be helpful.

How to Balance Cortisol Naturally

Similar to melatonin, a comprehensive approach to cortisol imbalances is important. One's practitioner will want to measure if cortisol is too high, which is often in more acute or subacute stress, or too low, which can occur in chronic stress. Both can be modulated by lifestyle and integrative medicine practices.

Lifestyle Factors

Lifestyle factors to modulate cortisol include:

• Sleep: Chronic sleep issues are associated with higher cortisol levels.
• Exercise: Several studies have shown that regular exercise helps improve sleep quality and reduces stress, which can help lower cortisol levels over time.
• Learning to limit stress and stressful thoughts.
• Deep breathing exercises: These practices can help to stimulate the parasympathetic nervous system, your "rest and digest" system, leading to lower cortisol levels.
• Fun and Laughing: Laughing stimulates the release of endorphins and lowers cortisol. Having fun can also act to boost mood and lower stress.
• Healthy relationships: Unhealthy relationships can cause frequent stress and raise cortisol levels.
  

Aromatherapy

Clary Sage Oil, Bergamot Oil, and Lavender Oil all have evidence in small clinical trials to lower cortisol levels.

Food and Diet

Certain foods can help with the effects of stress and cortisol. Eating an anti-inflammatory diet that contains foods high in the following nutrients can help fuel the body to cope with catabolic changes from stress:

• B vitamins (e.g., beef, chicken, eggs, and grains)
• Omega-3 fatty acids (e.g., salmon, avocados, and nuts and seeds)
• Magnesium (avocados, bananas, broccoli, dark chocolate, and pumpkin seeds)
• Protein-rich foods (nuts and seeds, meats, fish, and poultry)
• Gut-healthy foods (kefir, Greek yogurt, kimchi, sauerkraut, and kombuchu. Note: these foods are histamine releasing)
  

Herbs and Supplements

• Herbs that are calming and help the body adapt to stress (adaptogens) can help modulate cortisol.
• If one is particularly stressed and anxious, herbals that help regulate the calming neurotransmitter GABA, such as Valeriana officinalis (valerian), Matricaria recutita (German chamomile), Humulus lupulus (hops), can be helpful.‍
• Ashwagandha has stress-relieving properties due to its potential to regulate the hypothalamus-pituitary-adrenal axis (HPA axis), which impacts the stress response. 300 mg of ashwagandha root extract taken for 60 days was found to reduce cortisol in participants with chronic stress levels in one placebo-controlled study. It also enhanced the subjects' overall stress resistance and energy levels. Another clinical trial with ashwagandha root extract at 250mg and 600mg dosages was also found to reduce perceived levels and cortisol levels in healthy adults.
• Rhodiola Rosea is another herb that has support for assisting stress-related fatigue. One review article on Rhodiola reported its benefits in managing many different aspects of stress, including burnout.
• In a randomized, placebo-controlled trial, holy basil significantly reduced stress after six weeks.‍
• L-theanine, an amino acid extracted from green tea, has been found in a systematic review to reduce stress in those with acute anxiety.‍
• Phosphatidylserine (PS), another amino acid derivative found in high amounts in the brain, also has some evidence for lowering cortisol and enhancing cognitive function.
  

FAQ About Melatonin and Cortisol

Below are some common questions about Melatonin and Cortisol:

How Much Melatonin Should I Take?

Melatonin dosage has yet to be standardized. Physiologic doses of 0.3 mg have been suggested for addressing sleep disorders, whereas 300 mg have been used for certain neurodegenerative conditions. In research, ranges from approximately 0.3 to 5 mg per day have been used. The smaller dose possible for effects is recommended. (1, 26-27)

What Does Melatonin Do?

Melatonin regulates various functions and processes in the body, including (1-5, 26-27)

• Body Mass
• Body temperature
• Digestive Health
• Inflammation and antioxidant status
• Bone health
• Circadian rhythm (e.g., sleep-wake rhythm)
• Neurodevelopment
• Reproduction and endocrine health
• Some human studies support its beneficial effects for high blood pressure, polycystic ovarian syndrome (PCOS), certain cancers, jet lag, and sleep disorders.
  

How Long Does Melatonin Supplementation Last?

After an oral dose of 1 to 5 mg, baseline serum melatonin levels return to normal in four to eight hours.

What Are Normal Cortisol Levels?

For most tests, the average blood ranges are:

• 6 a.m. to 8 a.m.: 10 to 20 micrograms per deciliter (mcg/dL).
• Around 4 p.m.: 3 to 10 mcg/dL.
  

Salivary lab cortisol markers can range depending on when the sample was taken. In one study with 129 healthy subjects, the reference interval for morning and late-night salivary cortisol was 2.09 - 22.63 nmol/L and <12.00 nmol/L, respectively.

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Summary

Melatonin has been touted as the "sleep hormone" and cortisol as the "stress hormone," yet they are so much more. Melatonin and cortisol are key regulator hormones in the body with a wide range of far-reaching effects. Both have receptors throughout the body, and their impact can have system-wide effects. Beyond their effect on sleep and stress-related processes, their balance is essential for many physiological processes.

Balancing melatonin and cortisol by regulating lifestyle processes, decreasing stress, and supplementing when appropriate can optimize health and benefit many body systems.