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Environmental toxins are beyond the scope of this article and website; however, consumers, clinicians, and media outlets are becoming increasingly aware of the growing health concerns for people and the planet due to exposure to environmental toxins, such as herbicides.

Melatonin is well-established as a potent antioxidant and, as a result, can impact many areas of health, including neurological health and supporting the glymphatic system to aid in clearing toxins from the brain. Clinically, this study serves as a reminder to inquire about exposure to herbicides (and other environmental toxins), as this may impact melatonin production and suggest an increased need for this ubiquitous molecule. When considering supplementation, plant melatonin was found to be a more potent scavenger of free radicals compared to synthetic melatonin.

While melatonin may not be the first therapy considered for women experiencing menopausal symptoms, this study adds to the literature suggesting the use of 3 grams of melatonin in perimenopausal women for a wide array of climacteric symptoms and to reduce LH and FSH levels. Serum melatonin testing is not an ideal measurement since this only reflects the amount of melatonin circulating at the time of collection; however, the improvements in LH, FSH, and menopausal symptoms in 12 weeks were significant, suggesting melatonin could be used alone or in combination with other therapies for perimenopausal women.

Autism spectrum disorder (ASD) is a clinical condition for which the safety and efficacy of using melatonin have been established in the literature. This study highlighted these same findings with improved sleep parameters. In addition, it revealed that adherence to its use is good, and safety remains intact, with a mean of 88 months of use, which is much higher than some current safety studies report. This information could provide additional insight into the long-term use of melatonin in the ASD population.

Of note, using melatonin within the pediatric population for general sleep concerns, while safe, is not the first line of action that is recommended. Rather, employing sleep hygiene and behavior practices should first be considered.

We have previously reported that circadian patterns and melatonin levels are altered in women and adolescents with PCOS. This recent pilot study adds to the existing evidence that a misalignment in the circadian rhythm and, therefore, reduced sleep quality is present in women with PCOS. Clinically, it would be prudent to assess for sleep concerns in this population of women. Further, melatonin’s role in ovarian function was also suggested, supporting a previous review we reported on.

Melatonin has been cited in the literature for its use in various surgical procedures such as reducing pain following back surgery and reducing sepsis following surgery. The exploration of melatonin therapy for c-section pain is clinically relevant since over 32% of all women undergo cesarean section for childbirth. Due to melatonin’s safety profile, the use of melatonin pre-operatively to assist in pain management may be a plausible therapy for surgeons and clinicians to consider, with the greatest benefit resulting from a single dose of 10 mg of melatonin prior to surgery.

At present, there is mixed evidence for the use of melatonin as a potential therapy for IBD with 50 publications in Pubmed using the search terms “inflammatory bowel disease” and “melatonin” (as of May 11, 2023). Of these publications, there is limited clinical data to suggest that melatonin supplementation may be therapeutic for those with IBD. This is an animal (mouse) study that needs to be viewed within the larger context of existing research, concepts, and application of melatonin in IBD, which encompasses both ulcerative colitis and Crohn’s disease.

“In conclusion, we are grateful to Dr. Pluta for raising the question about the similarities between vitamin D and melatonin and whether the two may be seen as having identical functions, particularly for brain and neurological health. To reiterate, while we would not want to suggest that the two are interchangeable, we documented that they could target common mechanistic pathways underlying the pathologies of several chronic diseases and even foster healthy brain aging.”

This article supports the emerging literature on melatonin’s mechanism of action through the GI tract, along with its antioxidant activities. Enterochromaffin cells in the gut contain approximately 400 times more melatonin than what is produced in the pineal gland. This release of melatonin in the gut increases gastric mucosa and gut motility and has been shown to have a protective effect on the GI tract via its antioxidant activities. The data from the 4 RCTs provide a foundation to consider melatonin as a therapy for patients with IBS. A clinician should carefully assess the individual and make recommendations according to their personalized needs. Three of the four studies included the dose of 3 mg melatonin at bedtime, which aligns with other studies reported in a review article.

The use of melatonin in children for sleep concerns is a topic we have routinely examined, reported on, and reviewed as literature becomes available. We agree that other approaches, especially sleep hygiene, should be addressed first prior to melatonin therapy considering that endogenous production of melatonin is high in this age group. This short-term study does support existing literature that demonstrates the safety profile of melatonin in children, with a maximum dose of 3 mg for children and 5 mg for adolescents, in those who need it. The use of melatonin for children should always be discussed with the child’s physician before starting supplementation.

Based on the data presented in this article, combined with other articles our team has reviewed, we contend that the research on melatonin for PMS and PMDD is an emerging area to monitor. At present, clear clinical guidelines for the dose and timing of melatonin for this specific health concern have not yet been established, however, based on preliminary data, it appears promising and aligns with other research...

This narrative review has provided a comprehensive summary of the multitude of ways melatonin is beneficial for fertility, whether conceiving naturally or using assisted reproductive techniques, with key points that can be shared with patients in a clinical setting. Additionally, for women with endometriosis or PCOS, a dose of 3 mg melatonin per day has been demonstrated to improve multiple aspects of hormonal health that may improve fertility outcomes. In clinical practice, our team has used 5 mg of melatonin for PCOS.

This narrative review summarized current evidence and reported that melatonin is a safe therapy for sleep disorders in older adults, with non-statistical significance in reported adverse effects, of which the most common are headaches, daytime fatigue, and dizziness. It is best used at the lowest therapeutic dose (<1 mg), administered 30-60 minutes before bed. Since older adults are more likely to have other health conditions and take one or more prescription medications, it is prudent for clinicians to check for possible drug interactions and monitor patients after starting melatonin therapy. Aspects of monitoring include but are not limited to, blood pressure, daytime fatigue, labs (i.e., prothrombin time for those on warfarin), and sleep quality.

This article provides a comprehensive summary of the possible mechanisms for action, each of which could be explored in greater detail in future human studies. While specific dosing of melatonin is not described in this review article, the clinical usefulness of understanding the possible mechanisms of action allow clinicians to implement this knowledge to consider melatonin as an option for the management of anxiety disorders.

This review provides an overview of the use of melatonin for sleep disorders in psychiatric illnesses and it may provide guidance to clinicians on possible doses of melatonin for select conditions.

While this article provides a deeper explanation of the role of oxidative stress in the pathophysiology of stroke, we are focused on details reported on the potential use of melatonin for stroke. Our main takeaway from this article is that melatonin continues to be highlighted in the literature for its antioxidant properties. The findings in the animal studies and limited human clinical trials are promising, though, we agree with the authors, that more studies are needed to determine the proper clinical application of melatonin in stroke patients

High-dose IV melatonin administration improved clinical outcomes of ICU patients with sepsis that required surgery. While further studies are needed for the delivery and dose of melatonin for this purpose, the antioxidant and anti-inflammatory properties of melatonin appear to show promise as a possible adjuvant therapy for those with sepsis. Though melatonin is not being suggested as a standalone therapy for sepsis, we would stress the importance of utilizing all needed medical therapies to manage sepsis and all other infections. Our key takeaway from this article is that this study provides additional insight into the variation of dosing and delivery forms of melatonin that can be utilized clinically. 

Using oral melatonin was shown to be significant in reducing post-operative pain following a lumbar laminectomy/discectomy compared to placebo. Interestingly, while each of the three melatonin-treated groups reported less pain than the placebo group, there was not a significant difference in the pain reported between the melatonin-treated groups. Thus, the biggest takeaway from this article is that the model of using the lowest, most effective dose of melatonin for this clinical purpose may be best. 

We understand that essential hypertension has a complex pathology with many factors that impact development including but not limited to genetics, diet, and stress, and are aware that one therapy option is not a likely solution to this disease that impacts billions of people worldwide.  With arterial stiffness being an indicator of cardiovascular morbidity and mortality, any improvement can be of clinical value

This is an area of melatonin research we will be monitoring with excitement. As the incidences of chronic diseases continue to rise, the need to effectively manage the diseases and improve the quality of life for those living with the diseases is of great interest. While it is too soon to provide clinical application, melatonin may be a plausible adjuvant to MSC therapy due to its mitochondria-regulating properties

Clostridioides difficile (C. difficile) pathogenesis has a strong association with inflammation. One function of melatonin is that it is a powerful anti-inflammatory and antioxidant, with existing research demonstrating the benefits for GI health, making it a reasonable choice as a potential therapy to aid in lowering inflammation.​