Written by Dr. Kim Ross, Doctor of Clinical Nutrition
Dr. Kim Ross is passionate about women's health, sleep, gut health, and mental well-being. She is the founder of Ross Nutrition Team, a virtual nutrition consulting clinic, a researcher with multiple peer-reviewed publications, adjunct faculty, and a mentor to students and aspiring Certified Nutrition Specialists (CNS).
Melatonin is commonly known for its role in regulating sleep. But did you know melatonin is more than a hormone or dietary supplement? It is also a powerful antioxidant, anti-inflammatory agent, and mitochondria regulator. As a result, melatonin has emerged as a potential therapeutic option in promoting healthy aging and managing various age-related diseases.
What does ‘healthy aging’ really mean?
The terms longevity, anti-aging, and biohacking (among others) are hot buzzwords in the health and wellness scene. Everyone’s definition and mission around this topic can vary. I believe that most people seek to age in a healthy manner or age gracefully, free from many of the common ailments and chronic diseases in the aging population.
The World Health Organization describes healthy aging like this,
“Healthy aging is a continuous process of optimizing opportunities to maintain and improve physical and mental health, independence, and quality of life throughout the life course.”
Aging is often thought of as a person’s biological age increasing over time. While this is one aspect, the aging process is also accompanied by cellular changes that occur over time. Some changes may occur quickly after a highly stressful event or severe illness, for example, or the changes may occur slowly over time, as nature intended.
The aging process is influenced by many factors, such as:
Genetics
Physical and social environments
Social interactions (personal and in the community)
Socioeconomic status
Gender
Ethnicity
Use of tobacco
Use of alcohol
Dietary intake
Physical activity
Personal attitude
Spirituality
Stress
Combined, these factors ultimately determine how healthy (or not) the aging process will be. According to the World Health Organization, by 2050, individuals aged 60 years and older will constitute 22% of the global population, emphasizing the need for strategies to support healthy aging.
What does melatonin have to do with aging?
As mentioned, melatonin is a hormone for sleep but also a powerful antioxidant, anti-inflammatory agent, and mitochondrial regulator. As people age, each of these functions can be negatively impacted. For example, people may sleep less, have more inflammation, or be diagnosed with one or more diseases connected to mitochondrial dysfunction. In fact, all chronic diseases share one or more of these features.
A gradual decline in melatonin production accompanies biological aging. The body’s production of melatonin peaks in childhood and gradually declines throughout adulthood. [1] Research indicates melatonin’s decline with age may influence the onset of diseases such as neurodegenerative disorders, cardiovascular diseases, and metabolic syndrome. [1]
Melatonin’s benefits for healthy aging
1. Sleep
You are likely most familiar with melatonin for sleep. The pineal gland (located in the brain) produces melatonin (the hormone) in response to darkness at levels between 0.1-0.9 mg per day. It is often called “the “hormone of darkness”. [1]
Melatonin production peaks at about 2 am and then slowly declines through the remaining morning hours, eventually leading to very low (no) production, causing you to wake up. [2] Cortisol, a hormone produced in the adrenal glands, begins to increase as melatonin decreases. Cortisol, in part, provides you with the alertness and energy to function throughout the day. (Chronic elevations of cortisol can occur from excessive stress, which is a topic for another time!) Cortisol peaks around 9 am and gradually declines throughout the day. There is a very delicate balance between melatonin production and cortisol production and, therefore a very intimate connection between sleep and stress.
Poor sleep and disruptions in the circadian rhythm have been referred to as a hallmark of aging. [3, 4] While sleep can be disrupted for several reasons, low melatonin production may be one of them; therefore, supplemental support may be required.
(I mentioned in another article that I am a “sleep snob,” so I will provide more on this topic in the future!)
2. Mitochondrial support
Mitochondria are referred to as the “powerhouse” of our cells. In part, they can produce melatonin based on the needs of the cells. Long-time researchers of melatonin hypothesize that the mitochondria are a primary site of melatonin production. [5] The mitochondria can also use melatonin made from the pineal gland or consumed in foods and supplements.
It has been reported that mitochondrial damage or dysfunction is one of the mechanisms related to diseases of aging. [4]
Many signs and symptoms have been connected to mitochondrial dysfunction, such as: [6]
Fatigue/low energy
Poor exercise tolerance
Muscle pain and weakness
Generalized pain
Generalized inflammation
Increased susceptibility to infection
Changes in cognition and mood
Headaches
Multiple diseases have also been connected to mitochondrial dysfunction, such as: [7]
Anxiety & Depression
Alzheimer’s disease & dementia
Parkinson’s disease
Cardiovascular disease (high cholesterol, hypertension)
Metabolic diseases (pre-diabetes, diabetes)
Autoimmune conditions
Arthritis
Melatonin levels in the mitochondria are higher than those found in the blood, likely due to the antioxidant requirements of the mitochondria, which leads me to melatonin’s next benefit.
3. Antioxidant support
Oxidative stress plays a crucial role in the development of age-related diseases. It has been implicated in obesity, dementia, vascular diseases, osteoporosis, and more. [8]
Antioxidants are substances that help to prevent oxidative stress and damage to cells. You have undoubtedly seen news about the importance of consuming antioxidant-rich nutrients, like Vitamin C and E, and foods like fruits, vegetables, beans, and dark chocolate.
Melatonin is a potent antioxidant that can: [9]
Prevent free radical formation, which creates damage to tissues and organs.
Scavenge free radicals that are formed- up to 10 times more efficiently than Vitamin C!
Repair damage caused by free radicals.
Lead to the production of more antioxidants like glutathione. [10]
Additionally, melatonin can be derived from the diet (foods and supplements) or produced within the body in the mitochondria, pineal gland, and other organs like the gut and skin. [1]
Unlike other antioxidants, melatonin is both water and fat-soluble. As a result, melatonin can travel to many parts of the body, including the blood (mostly water) and the brain (mostly fat), as well as cross cell membranes and protect all cellular compartments. [1] Some of the highest antioxidant activity in the body occurs at nighttime when you are asleep, and melatonin production peaks. [1] (Another win for good sleep.)
Melatonin’s unique role as an antioxidant is one of the reasons it could be considered a therapeutic agent for healthy aging. [11]
4. Anti-Inflammatory Agent
Inflammaging is a term describing how inflammation contributes to an accelerated aging process. [8] Chronic inflammation is connected to all chronic diseases and an unhealthy aging process. Melatonin has demonstrated significant anti-inflammatory properties, making it a sought-after therapy in research and clinical application. [12]
By default, you likely are familiar with one of the proinflammatory molecules called cyclooxygenase (COX-2). Many over-the-counter pain relievers, such as ibuprofen, work by blocking this inflammatory molecule. Melatonin is also known to block this molecule. [12] One study found that plant melatonin was far superior at inhibiting COX-2 compared to synthetic melatonin, with a 646% greater inhibition, ¹³ demonstrating that the source of melatonin matters.
Pulling it all together
Each of the four areas discussed is interconnected. Poor sleep can lead to inflammation. Inflammation can lead to mitochondrial dysfunction and increased oxidative stress. Mitochondrial dysfunction makes the body more inflamed and disrupts sleep and so on.
As a hormone, mitochondrial regulator, antioxidant, and anti-inflammatory agent, melatonin’s potential in health and healthy aging is vast. [1]
Should you eat melatonin-containing foods or take a supplement?
As a Doctor of Clinical Nutrition, I focus on food first. However, consuming enough melatonin-containing foods to meet the body’s demands can be challenging, making a supplement a feasible option.
There are many plant sources of melatonin-containing foods, such as tart cherries and pistachios. However, you would need to consume about 50 pounds of cherries or over 1,500 pistachios daily to get the physiological dose of 0.3 mg of melatonin. [1] Melatonin amounts are relatively lower in animal sources than in plants. Regardless, a whole-food, plant-forward dietary plan provides a plethora of health benefits and, therefore, is encouraged!
When melatonin supplementation is warranted, there are several things to consider:
Dose: The physiological dose of 0.3 – 1.0 mg is established in the literature to provide many benefits since this resembles the amount the body would make naturally. Higher doses of 3 mg or more may also be considered for certain conditions, but this should be discussed with your healthcare provider or nutritionist to determine if this is appropriate for you. [1, 14]
Source: Most melatonin supplements available commercially are synthetically made. Plant melatonin, as the name implies, comes from plants. Some benefits of choosing a plant melatonin include its ability to drastically reduce inflammation and scavenge free radicals compared to its synthetic counterpart. [13] Additionally, it contains other nutrients such as essential fatty acids, amino acids, several vitamins, minerals, and phytonutrients that occur naturally in plants. [1]
Quality: Ensuring quality control measures are in place is important with all supplements. Inquire about third-party testing for contaminants (commonly found in synthetic melatonin supplements) and how the manufacturer complies with good manufacturing practices, including how the supplement is packaged to ensure shelf life and stability. [1]
Safety: Oral melatonin is generally considered safe, with very few adverse effects reported. Most are reported at doses of 10 mg or higher. [15] With that said, melatonin can cause drowsiness (as intended) and can have some theoretical risks with certain medications.
Personal Note: My favorite melatonin option is Herbatonin by Symphony Natural Health*.
Summary
Melatonin is a multifaceted hormone with significant potential to promote healthy aging and longevity. Its broad range of actions, from antioxidant and anti-inflammatory effects to mitochondrial regulation, makes it a valuable therapeutic agent. As the global population ages, melatonin’s role in managing age-related diseases and promoting overall health is likely to become increasingly important.
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Read more from Dr. Kim Ross
Dr. Kim Ross, Doctor of Clinical Nutrition
Dr. Kim Ross is a respected clinician, educator, and researcher in the field of nutrition science. She has been in clinical practice (Ross Nutrition Team) since 2010, specializing in hormonal, mental, and gastrointestinal health, though she and her team of nutritionists work with a broad range of health conditions. In recent years, she has passionately pursued the completion of multiple peer-reviewed publications demonstrating the use of amino acid therapy and psychobiotics for mental health disorders and case reports and narrative reviews about the use of maca for women’s hormone health. She is on a mission to help transform, educate, and mentor individuals on the power of nutrition.
References:
Minich DM, Henning M, Darley C, Fahoum M, Schuler CB, Frame J. Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements. Nutrients [Internet]. 2022;14(19). Available here.
Tordjman S, Chokron S, Delorme R, Charrier A, Bellissant E, Jaafari N, et al. Melatonin: Pharmacology, Functions and Therapeutic Benefits. Curr Neuropharmacol. 2017;15(3).
Verma AK, Singh S, Rizvi SI. Aging, circadian disruption and neurodegeneration: Interesting interplay. Vol. 172, Experimental Gerontology. 2023.
Srivastava S. The mitochondrial basis of aging and age-related disorders. Vol. 8, Genes. 2017.
Tan DX, Manchester LC, Esteban-Zubero E, Zhou Z, Reiter RJ. Melatonin as a potent and inducible endogenous antioxidant: Synthesis and metabolism. Molecules. 2015.
Keogh MJ, Chinnery PF. How to spot mitochondrial disease in adults. Clinical Medicine, Journal of the Royal College of Physicians of London. 2013;13(1).
Diaz-Vegas A, Sanchez-Aguilera P, Krycer JR, Morales PE, Monsalves-Alvarez M, Cifuentes M, et al. Is mitochondrial dysfunction a common root of noncommunicable chronic diseases? Vol. 41, Endocrine Reviews. 2021.
Tan BL, Norhaizan ME, Liew WPP, Rahman HS. Antioxidant and oxidative stress: A mutual interplay in age-related diseases. Vol. 9, Frontiers in Pharmacology. 2018.
Mehta SK, Gowder SJT. Members of Antioxidant Machinery and Their Functions. In: Basic Principles and Clinical Significance of Oxidative Stress. 2015.
Pandi-Perumal SR, Srinivasan V, Maestroni GJM, Cardinali DP, Poeggeler B, Hardeland R. Melatonin: Nature’s most versatile biological signal? Vol. 273, FEBS Journal. 2006.
Srinivasan V, Maestroni GJM, Cardinali DP, Esquifino AI, Pandi Perumal SR, Miller SC. Melatonin, immune function and aging. Vol. 2, Immunity and Ageing. 2005.
Ashrafizadeh M, Najafi M, Kavyiani N, Mohammadinejad R, Farkhondeh T, Samarghandian S. Anti-Inflammatory Activity of Melatonin: a Focus on the Role of NLRP3 Inflammasome. Vol. 44, Inflammation. 2021.
Kukula-Koch W, Szwajgier D, Gaweł-Bęben K, Strzępek-Gomółka M, Głowniak K, Meissner HO. Is phytomelatonin complex better than synthetic melatonin? The assessment of the antiradical and anti-inflammatory properties. Molecules. 2021;
Scheer FAJL, Van Montfrans GA, Van Someren EJW, Mairuhu G, Buijs RM. Daily Nighttime Melatonin Reduces Blood Pressure in Male Patients with Essential Hypertension. Hypertension. 2004;43(2 I).
Tuft C, Matar E, Menczel Schrire Z, Grunstein RR, Yee BJ, Hoyos CM. Current Insights into the Risks of Using Melatonin as a Treatment for Sleep Disorders in Older Adults. Clin Interv Aging. 2023 Jan; Volume 18:49–59.
Disclaimers: Information provided in this article is for informational purposes only and is not intended to serve as a replacement for the care provided by medical doctors, psychologists, psychiatrists, or other healthcare providers. Supplements: Before beginning new supplements, check with your healthcare and medical providers. The FDA has not evaluated any data regarding supplements. These products are not intended to diagnose, treat, cure, or prevent any disease.
*Dr. Kim Ross is an independent contractor of Symphony Natural Health, providing medical, evidence-led content for consumers and healthcare professionals.
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