Serum and plasma leptin levels in patients with Multiple Sclerosis: A systematic review and meta-analysis

Increasing evidence indicates that leptin, an adipocyte-derived cytokine with strong immunomodulatory and pro-inflammatory properties, may play a role in multiple sclerosis (MS) pathogenesis through regulation of T helper cell balance and inflammatory cytokine signaling. However, findings from individual studies assessing circulating leptin levels in MS patients remain inconsistent and sometimes contradictory. This systematic review and meta-analysis aims to synthesize the available evidence and generate a more precise estimate of serum and plasma leptin levels in individuals with MS.

A comprehensive literature search of PubMed and Web of Science was conducted from database inception to March 26, 2026, following PRISMA guidelines. Studies were included if they reported quantitative serum or plasma leptin levels in MS patients and healthy controls. Two reviewers independently screened eligible records, while two reviewers extracted data and assessed study quality using a modified QUADAS tool. Pooled effect sizes were calculated as standardized mean differences (SMDs) using a random-effects model. Heterogeneity was evaluated using the I² statistic, and publication bias was assessed through funnel plot inspection along with Begg's and Egger's tests. Sensitivity analyses were performed using a leave-one-out approach.

Twenty-one studies including 2978 participants (1656 MS patients and 1322 controls) were analyzed. Overall, MS patients showed significantly higher circulating leptin levels than controls (SMD = 0.54, 95% CI [0.14, 0.95], p = 0.01) with a moderate effect size and substantial heterogeneity (I² = 95.82%). No publication bias was detected (Begg p = 0.19; Egger p = 0.23). Sensitivity analyses confirmed robustness of the pooled estimate. Subgroup analyses revealed no significant differences in leptin levels between female MS patients and female controls (SMD = 0.14, 95% CI [-0.08, 0.36]) or between male MS patients and male controls (SMD = -0.09, 95% CI [-0.86, 0.68]). In contrast, female MS patients had significantly higher leptin levels than male MS patients (SMD = 1.24, 95% CI [0.76, 1.73], p < 0.05). In relapsing-remitting MS, leptin levels did not differ significantly from controls (SMD = 0.39, 95% CI [-0.04, 0.83], p = 0.08), and sensitivity analyses indicated instability depending on study removal in this subgroup.

Circulating leptin levels are elevated in MS patients, suggesting a potential role in disease-related immune dysregulation. However, high heterogeneity and inconsistent subgroup findings limit firm conclusions, which highlights the need for further large, well-designed studies.