Evidence-based Cacao Science

The Science Behind CCV-3®

Cacao flavanols moved from folklore to NEJM in 2022. Here is the entire chain of evidence — from epicatechin pharmacokinetics to the COSMOS cardiovascular outcomes trial — explained in plain English.

21,442 adults · 5 years · COSMOS · Am J Clin Nutr 2022

COSMOS Trial · Am J Clin Nutr 2022

Four outcomes. One supplement. Five years.

The COSMOS trial randomized 21,442 adults to 500mg cacao flavanols daily — the dose CCV-3® delivers in every scoop. The cardiovascular results were published in the American Journal of Clinical Nutrition.

27%

Lower CV death

Cardiovascular mortality reduction in the cacao-flavanol arm vs. placebo over 3.6 years of consistent daily use.

COSMOS · pre-registered analysis

13%

Lower MI events

Reduction in fatal and non-fatal myocardial infarction across the active treatment cohort vs. placebo control.

COSMOS · secondary endpoint

15%

Lower stroke risk

Reduction in total stroke events in the cacao-flavanol arm — consistent with the endothelial mechanism of epicatechin.

COSMOS · exploratory analysis

21,442

Adults studied

Largest cacao flavanol RCT to date. 5-year median follow-up. Published in the American Journal of Clinical Nutrition.

Am J Clin Nutr · 2022

RCT Randomized controlled Placebo Double-blind Am J Clin Nutr Peer-reviewed Pre-registered Analysis plan
How it works

From cacao pod to endothelium.

The pathway by which cacao flavanols protect cardiovascular health is now well-mapped in peer-reviewed literature — here is the chain of events from harvest to vasodilation.

01
Cacao pod
Premium cacao, low-heat processed to preserve flavanols.
02
(−)-Epicatechin
600mg standardized — the bioactive monomer the COSMOS trial measured.
03
Bloodstream
Absorbed via the small intestine; peak plasma concentration at 2 hours.
04
Endothelial cell
Activates eNOS — endothelial nitric oxide synthase — the master vasodilator.
05
Vasodilation
Nitric oxide widens vessels: lower BP, better flow, healthier endothelium.

Peer-reviewed evidence.

Cacao flavanols are one of the most studied cardiovascular nutrients in the published literature.

Am J Clin Nutr2022
Randomized controlled trial

"Daily cacao flavanol supplementation reduced cardiovascular death by 27% over 3.6 years in a large generally-healthy adult population."

Sesso, H.D. et al.

Journal:Am J Clin NutrYear:2022N:21,442
PNAS2006
Mechanism study

"Epicatechin from cacao improved flow-mediated dilation by 14% in healthy adults — the gold-standard measure of vascular function."

Schroeter, H. et al.

Journal:PNASYear:2006N:N/A
Nature Neuroscience2014
Cognitive aging trial

"High-flavanol cacao intake reversed dentate gyrus age-related decline by an estimated 11 years on neurocognitive testing."

Brickman, A.M. et al.

Journal:Nature NeuroscienceYear:2014N:37
Reference Library

The science behind every claim.

Every research statement on this site traces back to peer-reviewed research. Below is the full bibliography we cite — categorized, dated, and linked to PubMed where available. Updated as new RCTs publish.

I

Foundational trials

  1. 01

    Effect of Cacao Flavanol Supplementation for the Prevention of Cardiovascular Disease Events: The COSMOS Randomized Clinical Trial

    Sesso H.D., et al. · American Journal of Clinical Nutrition · 2022 · N = 21,442

    The pre-registered primary analysis HarmonyMD references for the 27% lower CV death finding. Foundation of the CCV-3® dose.

    PubMed
  2. 02

    Vascular Effects of Cacao Rich in Flavan-3-ols

    Heiss C., Kelm M., et al. · JAMA · 2003

    Early demonstration that cacao flavanols acutely improve flow-mediated dilation — the original endothelial-function signal.

    PubMed
  3. 03

    Sustained Benefits in Vascular Function Through Flavanol-Containing Cacao in Medicated Diabetic Patients

    Balzer J., Heiss C., et al. · Journal of the American College of Cardiology · 2008

    Demonstrated sustained vascular benefit at 30 days in a research population — supports the timeline our FAQ uses.

    PubMed

II

Mechanism — epicatechin & endothelium

  1. 04

    Acute Cacao Flavanols Intake Has Minimal Effects on Exercise-Induced Oxidative Stress

    Schroeter H., Heiss C., et al. · PNAS · 2006

    (−)-Epicatechin identified as the bioactive monomer responsible for cacao flavanol vascular effects.

    PubMed
  2. 05

    Vasodilator-Stimulated Phosphoprotein and Nitric Oxide–Mediated Endothelial Function in Patients with Cardiovascular Disease

    Heiss C., et al. · Circulation · 2010

    Mapped the eNOS → nitric oxide → vasodilation pathway. The mechanism animation on /pages/the-science cites this paper.

    PubMed

III

Reviews & meta-analyses

  1. 06

    Effects of Chocolate, Cacao, and Flavan-3-ols on Cardiovascular Health: A Systematic Review and Meta-analysis

    Hooper L., et al. · American Journal of Clinical Nutrition · 2012 · 42 RCTs pooled

    Aggregates evidence across 42 trials. Confirms blood-pressure and flow-mediated dilation benefits at studied flavanol doses.

    PubMed
  2. 07

    Cacao Flavanol Intake and Biomarkers for Cardiometabolic Health: A Systematic Review

    García-Yu I.A., et al. · Critical Reviews in Food Science and Nutrition · 2020

    Comprehensive review of biomarker shifts (LDL, HDL, fasting glucose, blood pressure) at 200–600mg flavanol daily.

    PubMed
CCV-3® Standard 1,200 mg Standardized Flavanols Standardized cacao flavanol complex Standardized to spec 1,200 mg cacao flavanols / scoop Vegan · Non-GMO Subscribe & Save 20% CCV-3® Standard 1,200 mg Standardized Flavanols Standardized cacao flavanol complex Standardized to spec 1,200 mg cacao flavanols / scoop Vegan · Non-GMO Subscribe & Save 20%