Clinical Bottom Line: This meta-analysis suggests that the formulation of melatonin is critical for its effect on nocturnal blood pressure. While a pooled analysis of all included trials found no significant effect of melatonin on nocturnal blood pressure, a planned subgroup analysis revealed a clinically meaningful distinction:

• Controlled-Release (CR) Melatonin: Significantly reduced both nocturnal systolic blood pressure (by -6.1 mmHg) and diastolic blood pressure (by -3.5 mmHg) compared to placebo.

• Fast-Release (FR) Melatonin: Had no significant effect on either systolic or diastolic blood pressure.

The findings suggest that add-on CR melatonin may be an effective and safe strategy for patients with nocturnal hypertension, though this is based on a small number of short-term trials.

📈 Results

Summary of Results: The meta-analysis pooled data from seven trials with 221 participants.

• Overall Effect (All 7 Studies): When all melatonin formulations were combined, there was no statistically significant effect compared to placebo on:

  • Nocturnal Systolic BP: Mean Difference (MD) -2.25 mmHg (95% CI -6.94 to 2.45)

  • Nocturnal Diastolic BP: MD -1.36 mmHg (95% CI -4.01 to 1.29)

• Subgroup Analysis (By Formulation):

  • Controlled-Release (3 studies): Showed a statistically significant reduction in:

    • Nocturnal Systolic BP: MD -6.10 mmHg (95% CI -10.70 to -1.51; P =0.009)

    • Nocturnal Diastolic BP: MD -3.51 mmHg (95% CI -6.15 to -0.87; P =0.009)

  • Fast-Release (4 studies): Showed no significant effect on:

    • Nocturnal Systolic BP: MD -0.27 mmHg (95% CI -5.88 to 5.34; P =0.925)

    • Nocturnal Diastolic BP: MD -0.24 mmHg (95% CI -3.77 to 3.28; P =0.893)

In this analysis, the mean difference (MD) represents the change in blood pressure (in mmHg) for patients taking melatonin compared to those taking placebo; a negative value favors melatonin. The 95% confidence interval (CI) is the range in which the true effect likely lies. Because the CIs for the controlled-release group do not cross zero, the results are statistically significant.

🧐 Assertive Critical Appraisal

• Certainty of Evidence (GRADE Framework): The authors do not use the GRADE framework. However, the certainty of this evidence should be considered Low to Moderate. The positive finding for controlled-release melatonin is from a subgroup analysis (albeit pre-planned) based on only three small studies. The authors themselves appropriately conclude that “larger trials of longer duration be conducted” to confirm these benefits.

• Heterogeneity: The authors used a random-effects model, which is appropriate for combining studies with potentially different results. However, the paper does not report a formal statistic for heterogeneity (like I²). The forest plots visually suggest some differences between the studies’ results, reinforcing that a random-effects model was a suitable choice.

• Publication Bias: The authors do not describe any assessment for publication bias (e.g., using a funnel plot). This is a limitation, as missing unpublished studies with negative results could lead to an overestimation of the treatment effect.

• Risk of Bias in Included Studies: The methodological quality of the seven included studies was assessed as adequate. Two reviewers independently used the Jadad scale, and all included studies had a score of 3 or more (mean score of 3.8 out of 5), which was the authors’ threshold for inclusion.

• Reporting Quality Assessment (PRISMA): The review’s reporting is transparent. It includes a PRISMA-style flow diagram (Figure 1) detailing the study selection process. It also clearly describes the search strategy, including the database (PubMed), date range (1980-2010), and search terms (“melatonin, blood pressure, and clinical trials”).

🎯 Research Objective

The objective was to perform a meta-analysis to assess the effect of exogenous melatonin on nocturnal blood pressure and to test the hypothesis that the results might differ based on the melatonin formulation (fast-release vs. controlled-release).

This question can be broken down using the PICO framework:

• Population: Patients from randomized trials (including normotensive, hypertensive, diabetic, and coronary artery disease patients).

• Intervention: Exogenous melatonin (fast-release or controlled-release).

• Comparator: Placebo.

• Outcome: Nocturnal systolic and diastolic blood pressure, measured by 24-hour ambulatory blood pressure monitoring.

📖 Study Design

This is a meta-analysis of randomized controlled trials. The authors performed a search of the PubMed database for studies published between January 1980 and December 2010 and also screened reference lists of relevant articles.

They included studies that were:

• Randomized and placebo-controlled.

• Published in English.

• Used 24-hour ambulatory blood pressure monitoring (ABPM) to report nocturnal blood pressure.

They excluded open-label studies, studies that were not randomized or controlled, and studies using melatonin agonists.

👥 Setting and Participants

• Studies: Seven trials met the inclusion criteria and were included in the meta-analysis.

• Participants: The seven trials included a total of 221 unique participants. Due to crossover designs in some trials, the analysis included 344 total data points. The participant populations included 99 individuals with hypertension, 60 with coronary artery disease, 11 with type 1 diabetes, and 51 normotensive individuals.

📚 Bibliographic Data

• Title: Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials

• Authors: Ehud Grossman, Moshe Laudon, Nava Zisapel

• Journal: Vascular Health and Risk Management

• Year: 2011

• DOI: 10.2147/VHRM.S24603

Mandatory Disclaimer: This AI-generated analysis is for informational and research purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified health provider with any questions you may have regarding a medical condition.