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NMU 268 – More Evidence That Melatonin Supplementation Turns On Longevity Genes (SIRT1), Aids Fat-Burning in Overweight Subjects and Helps Protect Against Obesity-Induced Heart Damage

Nutrition/Natural Medicine Update No 268 (December 14, 2022)

with Dr. James Meschino

Topic:  More Evidence That Melatonin Supplementation Turns On Longevity Genes (SIRT1), Aids Fat-Burning in Overweight Subjects and Helps Protect Against Obesity-Induced Heart Damage

Source:  J Frontiers of Physiology (2020)


Many people know that melatonin levels decline as we age, which often results in poor sleep quality. As such, a growing number of adults now use melatonin as a sleep aid. In fact, the use of melatonin supplements has grown by more than 500 percent in the past two decades, from .4 percent in 1999–2000 to 2.1 percent of the population by 2017–2018 ( But most people are not aware of the other health and longevity benefits associated with melatonin supplementation. Melatonin is also an important antioxidant that is shown to protect many tissues, including the heart muscle and the brain. It also helps to regulate blood pressure and it helps to switch our metabolism into fat-burning mode. It even increases that activity or our brown fat, which helps us burn-off excess calories we may have consumed through the day and releases that energy as heat to the environment (thermogenesis), helping to prevent and combat weight gain.,bodyweight%20reduction%20and%20glycemic%20improvement.

Melatonin also helps to favorably modulate insulin, leptin, and lipid secretions, all of which help to prevent weight gain and type 2 diabetes. Melatonin also indirectly suppresses the release of inflammatory cytokines, helping to prevent and better manage age-related arthritic conditions. Melatonin also indirectly stimulates the synthesis of two other important antioxidants (glutathione and heme-oxygenase-1) that protect our tissues from free radical damage linked to aging and cancer. As well, prostate, breast cells, and certain immune cells have melatonin receptors, and when they are stimulated by melatonin it blocks key steps in cancer development in the prostate and breast, and it enhances immune system function. (1)

Regarding fat-burning and weight loss, a 2014 study involving 56 postmenopausal women clearly showed that the addition of 5 mg melatonin supplementation to a standard weight loss diet significantly improved weight loss results in the group provided with the melatonin compared to the non-supplemented group. The marked reduction in weight and BMI occurred in just a 16-week period. The BMI reduction dropped from approximately 29 down to 27. This is a significant drop in just 16 weeks. The authors of this study also cited research indicating that lower levels of melatonin secretion in the autumn-winter period can increase appetite and lead to weight gain. This is another reason to consider melatonin during the fall and winter periods – to help prevent weight gain (2). In 2020, an animal model, published in the journal Frontiers of Physiology, showed another important effect of melatonin in preventing heart damage that typically occurs in cases of obesity. In essence, the obese mice given melatonin supplementation showed less obesity-induced heart damage than the obese mice not given melatonin (who showed higher heart weight, heart hypertrophy, and had higher blood pressure). Melatonin supplementation in obese mice also helped to prevent damage to the heart muscle’s mitochondria (where energy is synthesized to keep the heart pumping) and it reduced heart muscle inflammation. The researchers explained that melatonin turns on a key anti-aging, disease-prevention, and longevity gene known as Sirtuin1.

Once turned on by melatonin the sirtuin1 enzymes act as epigenetic switches that turn on:

  • Fat-burning and blood sugar-regulating genes
  • Blood pressure regulating genes – helping to prevent the development of high blood pressure
  • Synthesis of antioxidants (glutathione and heme oxygenase-1), which protect cells from free radical damage, including the heart muscle and brain cells.
  • Mitochondria biogenesis – producing new and healthy mitochondria in the heart muscle and other tissues like the brain.
  • And melatonin turns off inflammation-promoting genes.

The researchers stated, “We conclude that the SIRT1/PGC-1α/Nrf2/HO-1 pathway represents a vital target in the quest to prevent adverse obesogenic cardiac remodeling (1). This means that melatonin supplementation, through its activation of the SIRT1 Longevity Gene, helps to prevent heart damage that is typically caused by weight gain, high-fat diets, and obesity and that this effect probably occurs in humans. In 2017, a report in the journal Pineal Research revealed that melatonin stimulates the SIRT1 longevity gene and through this action imparts protective effects against aging, neurodegenerative conditions (Alzheimer’s disease, Parkinson’s disease, etc.), and cancer, and favorably impacts immune system function. (3)

I think the take-away message from all these studies is that it may be wise to use melatonin as a supplement for general anti-aging purposes by the age of 40 to help reduce risk of various age-related diseases and to support your immune system function (helping to guard against infections and cancer). As well, melatonin also helps improve fat-burning and can enhance the results of weight loss programs of all types. It also appears to help prevent some key aspects of heart damage that typically occurs in overweight individuals, which may help to reduce the risk of heart attack and congestive heart failure commonly seen in this high-risk group. Of course, melatonin helps to improve sleep quality, but its anti-aging, anti-neurodegenerative disease, anti-inflammatory, immune modulating, antioxidant-stimulating, fat-burning and anti-diabetic effects, make it a strong supplement consideration even for those of us who do not have have sleep issues. Certainly, the discovery that melatonin supplementation activates key longevity genes, Sirtuin-1 (as well as Sirtuin-3) is a very significant discovery in recent years.

I have included the references for this information in the text below.


1. Sirtuin1 role in the melatonin protective effects against obesity-related heart injury. Frontiers of Physiology. March 11, 2020.

2. Walecka-Kapica E et al. The effect of melatonin supplementation on the quality of sleep and weight status in postmenopausal women. Prz Menopauzlny. 2014; 13(6): 334-338

3. Mayo JJ.C. et al. Melatonin and sirtuins: A “not-so unexpected” relationship. J Pineal Research. January 21, 2017.


Eat Smart, Live Well, Look Great,

Dr. Meschino

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