HDL cholesterol

Method

Serum or plasma high-density-lipoprotein cholesterol concentration by direct clinical assay, either a precipitation method or a homogeneous method. The method is recorded on the edge.

The method is part of the endpoint identity. Studies measuring the same quantity by a different method are held as separate endpoints.

Notes

SIGN INVERSION against LDL cholesterol and against total cholesterol. Same matrix, same draw, same unit, same lipid panel, opposite polarity: this endpoint improves by RISING and both of those improve by FALLING. This is the single most damaging merge available in the lipid panel. Note also that the unit is not recoverable from the construct name — PMID 36336325 reports mg/dL and the EPA meta-analyses report mmol/L — so every edge must carry its unit explicitly.

Findings

3 findings from 3 compounds, strongest first.

• resveratrol — no detected effect on

  AWell establishedGrade A, Well established. Replicated human trial evidence, consistent direction.FindingNull result

  “Compared with the placebo, resveratrol did not improve HDL-C levels (WMD: −1.05 mg/dL, 95% CI: −2.44, 0.33; P=0.14;.”

  Study

  meta-analysis

  Participants

  837

  Dose

  8.1-3000 mg/day resveratrol across the pooled trials

  Population

  Adults with type 2 diabetes; secondary endpoint, 14 pooled RCTs, resveratrol vs placebo

  Effect -1.05 mean difference, 95% CI -2.44 to 0.33

  Effects of Resveratrol on Metabolic Indicators in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.2022PMID:35685602

• curcumin — no detected effect on

  BLikelyGrade B, Likely. Human evidence, limited replication or design limits.FindingNull result

  “However, the pooled effects of curcumin supplementation on LDL, HDL, and TG were not statistically significant regardless of its forms, see Supplementary Appendix S–U.”

  Study

  meta-analysis

  Population

  adults with metabolic dysfunction-associated fatty liver disease (MAFLD/NASH); additional (non-liver-enzyme) outcome of the updated meta-analysis, pooled across 10 trials

  An updated meta-analysis of effects of curcumin on metabolic dysfunction-associated fatty liver disease based on available evidence from Iran and Thailand.2023PMID:37037891

• melatonin — increases

  BLikelyGrade B, Likely. Human evidence, limited replication or design limits.Finding

  “HDL-C levels were substantially increased (WMD: 2.04 mg/dL, 95% CI: 0.50, 3.57) following melatonin supplementation.”

  Study

  meta-analysis

  Dose

  0.3-100 mg/day oral

  Population

  adults in 63 RCTs of melatonin supplementation vs placebo across mixed clinical populations

  Effect 2.04 mean difference, 95% CI 0.5 to 3.57

  Comprehensive Effects of Melatonin Supplementation on Cardiometabolic Risk Factors: A Systematic Review and Dose-Response Meta-Analysis.2025PMID:41515249