Total cholesterol (TC)

Method

Serum or plasma total cholesterol (TC) concentration by clinical enzymatic cholesterol-oxidase assay.

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

Notes

Confusable with LDL cholesterol, and the confusion is not benign: this value is the SUM of the LDL, HDL and VLDL fractions, so it is independent of neither. An intervention that raises HDL-C while lowering LDL-C can leave this number flat, and one that raises HDL-C alone pushes it in the apparently harmful direction — PMID 39647241 shows exactly that pattern. PARTIAL SIGN CONFLICT with HDL cholesterol for that reason: HDL improving by RISING drags this endpoint the way its own direction of benefit calls harm. Never substitute for LDL-C in either direction.

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

  “The pooled effect estimate revealed no effect of resveratrol on cholesterol (MD = -5.91; 95% CI [-18.54, 6.72], P = 0.36).”

  Study

  meta-analysis

  Participants

  108

  Dose

  1000 or 1500 mg/day oral resveratrol

  Population

  Women with polycystic ovary syndrome; 2 pooled RCTs, resveratrol vs placebo

  Effect -5.91 mean difference, 95% CI -18.54 to 6.72

  Efficacy of resveratrol in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized clinical trials.2023PMID:37333786

• melatonin — decreases

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

  “The meta-analysis indicated that melatonin supplementation significantly reduced serum TC (WMD: −6.97 mg/dL, 95% CI: −12.20, −1.74) and LDL-C levels (WMD: −6.28 mg/dL, 95% CI: −10.53, −2.03) in the melatonin group compared with the control group.”

  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 -6.97 mean difference, 95% CI -12.2 to -1.74

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

• curcumin — decreases

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

  “Curcumin supplementation resulted in a significant reduction in total cholesterol and LDL-C levels when compared to the placebo group at the 6, 9, and 12-month time points.”

  Study

  RCT

  Duration

  12 months

  Dose

  Oral ethanolic Curcuma longa rhizome extract standardised to 75-85% total curcuminoids, 250 mg curcuminoids per capsule, three capsules twice daily (1500 mg curcuminoids/day) for 12 months

  Population

  Obese adults with type 2 diabetes mellitus managed on metformin (age >=35 y, BMI >=23 kg/m2, HbA1c <6.5%), Nakhon Nayok, Thailand; 227 randomised, per-protocol analysis and the analysed count is not reported in the paper; secondary endpoint (declared primary outcome: liver steatosis by controlled attenuation parameter on transient elastography)

  Curcumin Attenuates Liver Steatosis via Antioxidant and Anti-Inflammatory Pathways in Obese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial.2025PMID:41096556Industry funded