BY Samuel Mathis, MD, MBA, CPE, Family Medicine, UTMB-Health and the John Sealy School of Medicine
One of the most challenging integrative visits we face is patients with insomnia. It is often difficult to implement sleep hygiene recommendations in today’s busy society, and many prescription medications carry significant risks, especially in older patients. Two supplements we regularly recommend are melatonin and magnesium. Patients will often ask which of the two is a better choice for sleep. A growing amount of evidence has shown benefits with both supplements, though for different reasons.
Magnesium works through the modulation of GABA receptor activity. It potentially dampens cortical hyperarousal in patients with stress-related or “tired but wired” insomnia. Magnesium works differently from sedatives, which increase sedation to bring on sleep. Magnesium helps to improve the physiological conditions needed for sleep. A 2025 randomized, double-blind, placebo-controlled trial found that patients who took magnesium bisglycinate for 4 weeks had significantly improved Insomnia Severity Index scores compared to placebo (-3.9 vs -2.3) (1). Participants took 250mg of elemental magnesium nightly. Participants were also seen to have improved objective sleep parameters such as improved deep sleep, sleep efficiency, and REM duration. The study also noted that patients with lower baseline dietary magnesium intake seemed to have greater improvement. This indicates that magnesium-deficient patients may be better responders to this treatment and raises the question of whether magnesium labs should be considered in patients with insomnia.
The type of magnesium used also seems to play a role. A comparative study of multiple magnesium forms found that magnesium bisglycinate had the best absorption and the fewest side effects. Magnesium oxide and magnesium citrate are known to increase the risk of GI upset and diarrhea, which can impact compliance.
Alternatively, Melatonin has been widely studied for its impact on sleep. A recent 2022 systematic review found that in adults without comorbid conditions, melatonin was not significantly effective in sleep onset, total sleep time, or sleep efficiency (2). They did find that it was effective in children and adolescents and helped adults with comorbid insomnia for sleep onset latency associated with shift-work. This lends credence to the idea that melatonin helps with jet lag and shift work disorder, and when sleep is specifically affected by external activities or circumstances (2). The evidence is limited for melatonin’s regular use for insomnia.
It is important to pause here to discuss the safety concerns associated with any supplement used for sleep. Any medication that potentially causes drowsiness should be used with caution in older adults. Neither melatonin nor magnesium is listed on the Beers criteria list, but they should be used with caution.
A 2022 systematic review in the Journal of Clinical Medicine compared melatonin and ramelteon in older adults. The study found mild improvement in sleep, but did increase the risk of cognitive impairment, delirium, falls, and fractures with the use of ramelteon and other associated hypnotics (3). They also found a possible link between melatonin use and falls in older adults. When we consider the limited efficacy and increased risk of falls, melatonin use should be considered in only certain specific cases and potentially not used at all in adults over the age of 55.
In practice, magnesium bisglycinate should be used with 250 mg- 400 mg dosing at night. It is a reasonable first-line agent, especially in individuals with concern for low magnesium intake or low magnesium levels. I do not recommend testing magnesium levels in patients without symptoms of hypomagnesemia. Magnesium is preferred over melatonin in adults over the age of 55. For melatonin, the adage “less is best” holds true.
Melatonin should be dosed at 0.3mg to 3mg total before bed. Some studies have found that higher doses do not improve efficacy and can worsen side effects of the supplement, with increased daytime fatigue and altered dreams. Melatonin should be considered under specific circumstances instead of nightly use.
It is important to note that these supplements do not substitute for proper behavioral sleep interventions such as sleep hygiene and Cognitive Behavioral Therapy for Insomnia (CBT-I). There is significant evidence that proper sleep hygiene and CBT-I can have profound impacts on the quality and quantity of sleep when appropriately implemented. Some basic sleep hygiene recommendations include a consistent sleep and wake schedule, a cool bedroom environment (69 degrees F), and removing electronics (TV, phone, tablet, etc.) from the bedroom. CBT-I can help patients who are prone to overthinking when they go to sleep and help them relax into sleep instead of attempting to force it. t
References:
1. Schuster J, Cycelskij I, Lopresti A, Hahn A. Magnesium Bisglycinate Supplementation in Healthy Adults Reporting Poor Sleep: A Randomized, Placebo-Controlled Trial. Nat Sci Sleep. 2025;17:2027-2040.
2. Choi K, Lee YJ, Park S, Je NK, Suh HS. Efficacy of melatonin for chronic insomnia: Systematic reviews and meta-analyses. Sleep Med Rev. 2022;66:101692.
3. Marupuru S, Arku D, Campbell AM, Slack MK, Lee JK. Use of Melatonin and/or Ramelteon for the Treatment of Insomnia in Older Adults: A Systematic Review and Meta-Analysis. J Clin Med. 2022;11(17):5138.
Adapted from a review by Kade A Thompson, UTMB MS4.