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

Referenced research

The research that started it.

COSMOS studied 500mg cocoa flavanols daily in 21,442 adults over a multi-year window, published in the American Journal of Clinical Nutrition. HarmonyMD is our own high-potency ritual — 1,200mg cacao flavanols with 600mg epicatechin per scoop. HarmonyMD is not the COSMOS product.

21,442

Adults studied

The largest cacao flavanol trial to date, with a multi-year median follow-up, published in the American Journal of Clinical Nutrition.

COSMOS · Am J Clin Nutr 2022

1,200mg

Cacao flavanols per scoop

HarmonyMD's high-potency daily dose, well above the 500mg studied in COSMOS.

HarmonyMD · per serving

600mg

Standardized epicatechin

The standardized flavanol HarmonyMD is built around, in every single scoop.

HarmonyMD · per serving

3.6yr

Median follow-up

A daily ritual is a long game. COSMOS followed participants across years of consistent daily use.

COSMOS · 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.
Reviewing cardiology study

Peer-reviewed evidence.

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

Am J Clin Nutr2022
Randomized controlled trial

"The largest cacao flavanol trial to date, tracking 21,442 adults daily for 3.6 years across multiple health outcomes. Published in the American Journal of Clinical Nutrition."

Sesso, H.D. et al.

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

"Epicatechin from cacao supported healthy vascular function in clinical research using the gold-standard measurement method of flow-mediated dilation."

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%