Nutritional supplements and inflammatory biomarkers in overweight/obese adults: systematic review and network meta-analysis of RCTs
This network meta-analysis of RCTs shows that multiple nutritional supplements reduce circulating inflammatory biomarkers in overweight or obese adults, with effect sizes varying by supplement and outcome, consistently favouring interventions over placebo.
| Population | Adults ≥18 years with overweight (BMI ≥25 kg/m²) or obesity (BMI ≥30 kg/m²), or equivalent Asian criteria |
|---|---|
| Intervention | 14 supplementation strategies: resveratrol, magnesium, vitamin D, zinc, probiotics, omega-3, alpha-lipoic acid (ALA), synbiotics, vitamin E, green tea extract, curcumin, vitamin D + magnesium, probiotics + ALA, probiotics + omega-3 |
| Comparator | Placebo, no supplementation, or usual care |
| Outcome | C-reactive protein (CRP); Interleukin-6 (IL-6); Tumor necrosis factor-alpha (TNF-α); Leptin; Adiponectin; Relative efficacy ranking among supplements (SUCRA/P-score); Network consistency (indirect vs direct evidence) |
Summary of findings
| Outcome | Effect | 95% CI | Certainty | Clinical relevance | Notes |
|---|---|---|---|---|---|
| C-reactive protein (CRP) | SMD negative (curcumin, probiotics, omega-3 vs placebo); 95% CI excluding zero per pairwise comparison; pooled estimates vary by node | — | High | — | |
| Interleukin-6 (IL-6) | SMD negative (resveratrol, curcumin, zinc vs placebo); 95% CI excluding zero for leading interventions | — | High | — | |
| Tumor necrosis factor-alpha (TNF-α) | SMD negative (curcumin, probiotics+ALA vs placebo); 95% CI variable across nodes; moderate heterogeneity | — | Moderate | — | |
| Leptin | SMD negative (probiotics, synbiotics vs placebo); 95% CI reported per comparison in source study | — | Moderate | — | |
| Adiponectin | SMD positive (vitamin D, magnesium vs placebo); 95% CI reported per comparison in source study | — | Moderate | — | |
| Relative efficacy ranking among supplements (SUCRA/P-score) | Curcumin ranked highest for CRP and TNF-alpha; omega-3 and probiotics ranked highest for CRP; indirect evidence-based ranking; CrI not consistently reported across all nodes | — | Moderate | — | |
| Network consistency (indirect vs direct evidence) | Inconsistency not fully excludable at all network nodes; sparse direct head-to-head evidence between active supplements | — | Low | — |
Context
Chronic low-grade inflammation is a central mechanism linking obesity to metabolic, cardiovascular, and type 2 diabetes risk. Prior meta-analyses assessed single supplements, preventing cross-intervention comparisons. An NMA integrating direct and indirect evidence from 14 interventions enables comparative ranking.
What the study showed
The NMA included studies published between 2000 and 2026 comparing 14 supplements vs. placebo for five inflammatory biomarkers. For CRP, curcumin, probiotics, and omega-3 showed the largest reductions vs. placebo (negative SMDs; specific values and 95% CIs per comparison reported in the source study). For IL-6, resveratrol, curcumin, and zinc showed a favourable direction. For TNF-α, curcumin and probiotics + ALA led in reduction. Leptin decreased with probiotics and synbiotics; adiponectin increased with vitamin D and magnesium. Most comparisons showed moderate to high heterogeneity.
How it was done
Systematic review and NMA of RCTs published in English (January 2000–January 2026), searched in PubMed, Embase, EBSCO, Web of Science, and Cochrane Library. Protocol registered at PROSPERO (CRD420261348823). Risk of bias assessed with RoB 2.0. Consistency analysis and meta-regression by intervention duration were performed.
Effect magnitude
Effect sizes (SMD) varied by supplement and outcome; the study does not report a single consolidated SMD. The most effective interventions for CRP and IL-6 showed negative SMDs with 95% CIs excluding zero, indicating statistically significant effects favouring supplementation.
Risk of bias
Risk of bias assessed with RoB 2.0; moderate to high heterogeneity across studies for multiple outcomes compromises precision of estimates. Inclusion of studies as short as 2 weeks and wide variation in doses, formulations, and populations (different ethnicities and BMI ranges) limit comparability. Indirect evidence in the NMA introduces additional uncertainty; network inconsistency cannot be ruled out at all nodes.
What this study does NOT prove
This NMA does not prove causality between inflammatory biomarker reduction and prevention of clinical metabolic diseases. Results are not generalisable to morbid obesity, children, adolescents, or individuals with established inflammatory conditions.
In clinical practice
Clinicians may consider curcumin, omega-3, and probiotics as supplements with the strongest evidence base for CRP and IL-6 reduction in overweight/obese adults, within an integrated care plan. Choice must account for dose, duration, and individual patient profile, as effects are modest and do not replace lifestyle intervention.
Limitations
Risk of bias assessed with RoB 2.0; moderate to high heterogeneity across studies for multiple outcomes compromises precision of estimates. Inclusion of studies as short as 2 weeks and wide variation in doses, formulations, and populations (different ethnicities and BMI ranges) limit comparability. Indirect evidence in the NMA introduces additional uncertainty; network inconsistency cannot be ruled out at all nodes.
What is still missing
Long-term RCTs (≥12 months) with hard clinical endpoints (cardiovascular events, incident diabetes) are needed to establish the clinical relevance of the observed biomarker reductions.
Technical appendix
Version history
- 1.0 · 2026-09-17 — Auto-generated under Evidence Standard v1.0