top of page

Melatonin and Cortisol that controls body’s watch and managing them

Strange that cortisol is at peak in morning and declines over the day and Melatonin starts in evening and declines over the night.

The interplay between stress and sleep is scientifically linked.

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. 

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.

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 vaster than the potent influence our circadian rhythm has on our health. 

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 signalling cascades, gut, and digestive health, and many additional regulatory pathways.

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.

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.  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.

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."


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.

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.

How to Balance Cortisol Naturally

Similar to melatonin, a comprehensive approach to cortisol imbalances is important.

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.


Clary Sage OilBergamot Oil, vetiver and Lavender Oil all have evidence in 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.


86 views0 comments


bottom of page