# Caffeic Acid (3,4-dihydroxycinnamic acid)

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/caffeic-acid-34-dihydroxycinnamic-acid
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-04-02
**Evidence Score:** 1 / 10
**Category:** Compound
**Also Known As:** 3,4-dihydroxycinnamic acid, 3-(3,4-dihydroxyphenyl)-2-propenoic acid, trans-caffeic acid, CA (abbreviation)

## Overview

Caffeic acid is a hydroxycinnamic acid polyphenol that exerts antioxidant effects through [free radical scaveng](/ingredients/condition/antioxidant)ing (0.90 ± 0.01 mM Trolox equivalents) and [anti-inflammatory](/ingredients/condition/inflammation) effects by suppressing COX-2, NF-κB, and IL-8 expression at concentrations as low as 10 µM. In preclinical models, it demonstrates anticancer activity across multiple cell lines — including inhibition of HIF-1α stabilization and PI3K/Akt/VEGF signaling in hepatocellular carcinoma at 20 µM — though human clinical trial data confirming these effects remain limited.

## Health Benefits

- **[Antioxidant Protection](/ingredients/condition/antioxidant)**: Caffeic acid scavenges free radicals with a measured DPPH activity of 0.90 ± 0.01 mM Trolox equivalents and exhibits iron-chelating activity of 75.80 ± 1.07%, reducing oxidative burden at the cellular level.
- **[Anti-Inflammatory](/ingredients/condition/inflammation) Activity**: At 10 µM, caffeic acid downregulates COX-2, IL-8, MCP-1, CRP, and VCAM-1 expression in human endothelial cells and colon myofibroblasts, attenuating key mediators of the inflammatory cascade.
- **[Neuroprotective Effect](/ingredients/condition/cognitive)s**: In rotenone-induced neuroinflammation animal models, caffeic acid at 5–10 mg/kg significantly reduced striatal COX-2 (baseline 3.28-fold elevation reduced), iNOS (10.82-fold elevation reduced), and NF-κB (3.2-fold elevation reduced), suggesting protective value in neuroinflammatory contexts.
- **Anticancer Potential**: Caffeic acid inhibits tumor-promoting pathways including PI3K/Akt, NF-κB/IL-6/STAT3, and VEGF across multiple cancer cell lines (hepatocellular, breast, lung, cervical), suppressing proliferation and metastatic migration at concentrations of 20–100 µM in vitro.
- **Epithelial–Mesenchymal Transition (EMT) Reversal**: At 100 µM, caffeic acid increases E-cadherin expression while decreasing vimentin in TGF-β-exposed cervical cancer cells, indicating a capacity to reverse a key driver of cancer invasiveness.
- **[Cardiovascular](/ingredients/condition/heart-health) Endothelial Support**: By reducing VCAM-1 and MCP-1 in endothelial cells, caffeic acid may limit monocyte adhesion and vascular inflammation, processes central to early atherosclerosis development.
- **Gastrointestinal Antioxidant Activity**: Caffeic acid reaches relevant colonic concentrations of up to 126 µM following dietary intake, potentially providing localized antioxidant and anti-inflammatory protection to the colonic epithelium.

## Mechanism of Action

Caffeic acid's [antioxidant](/ingredients/condition/antioxidant) mechanism relies on hydrogen atom transfer and single electron transfer from its catechol (3,4-dihydroxy) moiety, enabling direct neutralization of reactive oxygen and nitrogen species, complemented by metal chelation that prevents Fenton-type radical generation. Its [anti-inflammatory](/ingredients/condition/inflammation) activity is mediated through suppression of the NF-κB transcription factor, reducing downstream expression of COX-2, iNOS, IL-8, MCP-1, and CRP, while simultaneously decreasing endothelial VCAM-1 to limit leukocyte adhesion. In cancer cell models, caffeic acid destabilizes HIF-1α and reduces mortalin expression, thereby suppressing PI3K/Akt and VEGF signaling to limit angiogenesis and survival, while also blocking the NF-κB/IL-6/STAT3 axis and inhibiting MMP-9, which collectively reduce tumor invasion and metastatic potential. Absorption occurs via passive gastric uptake and intestinal active transport through monocarboxylic acid transporters (MCT), with plasma peak reached within one hour of ingestion.

## Clinical Summary

No published human randomized controlled trials specifically isolating caffeic acid as an intervention with defined efficacy endpoints have been identified in the current literature. Most mechanistic insights are derived from in vitro studies in human cell lines (HepG2, MCF7, H1299, MDA-MB-231, endothelial cells) and rodent models using oral doses of 5–15 mg/kg. Bioavailability data from human absorption studies indicate approximately 95 ± 4% absorption, with maximum plasma concentrations reached within one hour, suggesting favorable pharmacokinetics that warrant further clinical investigation. Confidence in clinical benefit remains low due to the absence of human efficacy trials, and extrapolation from cell culture concentrations to dietary or supplemental intake requires significant caution.

## Nutritional Profile

Caffeic acid is a non-nutrient secondary plant metabolite with no caloric, macronutrient, or conventional micronutrient value. Its bioactive profile is defined by its phenolic structure: a C6-C3 hydroxycinnamic acid backbone with a 3,4-dihydroxy (catechol) substitution pattern that confers [antioxidant](/ingredients/condition/antioxidant) capacity of 0.90 ± 0.01 mM Trolox equivalents (DPPH assay) and iron-chelating activity of 75.80 ± 1.07%. Dietary exposure is primarily indirect through its ester forms — chlorogenic acid (quinic acid ester) in coffee and rosmarinic acid (caffeic acid dimer ester) in herbs — with free caffeic acid released during gastrointestinal hydrolysis. Bioavailability is high (~95 ± 4%), with intestinal MCT-mediated active transport augmenting passive absorption, and colonic fermentation generating additional bioactive metabolites at concentrations up to 126 µM.

## Dosage & Preparation

- **Dietary intake (free and esterified form)**: Consumed naturally via coffee (9–87 mg/100 g), chokeberries (~645 mg/100 g dry weight), fruits, vegetables, and olive oil; no standardized recommended daily intake established.
- **Supplemental extract (standardized)**: Caffeic acid is available in polyphenol-rich plant extracts (e.g., green coffee extract, propolis extract); typical standardization ranges from 5–45% chlorogenic/caffeic acid content, with no clinically validated human dosage established for isolated caffeic acid.
- **Caffeic Acid Phenethyl Ester (CAPE)**: A bioactive ester derivative found in propolis, studied separately at experimental doses; not equivalent in pharmacokinetics to free caffeic acid.
- **Timing**: Given the rapid plasma peak (~1 hour) and fast clearance, repeated smaller doses every 2 hours would theoretically sustain plasma exposure, though no clinical protocol has validated this approach.
- **Animal study reference dose**: Anti-neuro[inflammatory](/ingredients/condition/inflammation) effects observed at 5–10 mg/kg in rodent models; direct human dose equivalence has not been established or validated.

## Safety & Drug Interactions

Caffeic acid at dietary concentrations found in food is considered safe for general consumption, but specific adverse effect profiles, toxicity thresholds, and maximum tolerated doses for isolated supplemental caffeic acid in humans have not been formally established in peer-reviewed clinical safety studies. Theoretical drug interactions exist based on its inhibition of cytochrome P450 enzymes and potential interference with iron absorption due to its chelating activity, suggesting caution in individuals using iron supplementation or medications with narrow therapeutic windows metabolized via CYP pathways. Its structural similarity to coumarins raises a theoretical, unconfirmed concern about additive effects with anticoagulant medications such as warfarin at high supplemental doses, though evidence from human studies is absent. Pregnancy and lactation safety data are unavailable, and supplemental use beyond dietary food-based intake is not recommended for these populations until safety data emerge.

## Scientific Research

The current body of evidence for caffeic acid consists predominantly of in vitro cell culture studies and animal model experiments, with no large-scale, placebo-controlled human clinical trials identified in the peer-reviewed literature to date. Preclinical in vitro data demonstrate mechanistically coherent [anti-inflammatory](/ingredients/condition/inflammation) and anticancer effects at defined micromolar concentrations (10–100 µM), though translating these concentrations to physiologically achievable human plasma levels remains an unresolved challenge. Animal studies at 5–15 mg/kg have shown statistically significant reductions in neuroinflammatory and skin cancer biomarkers, providing proof-of-concept but not clinical validation. The overall evidence base is classified as preliminary, warranting well-designed human pharmacokinetic and efficacy trials before therapeutic claims can be substantiated.

## Historical & Cultural Context

Caffeic acid, as a constituent of plants used medicinally for centuries, has an implicit traditional history embedded within herbs such as rosemary, thyme, sage, and echinacea — all rich in caffeic acid derivatives like rosmarinic acid — which were employed in European, Ayurvedic, and Traditional Chinese Medicine for their [anti-inflammatory](/ingredients/condition/inflammation), [antimicrobial](/ingredients/condition/immune-support), and wound-healing properties. Propolis, the resinous bee product rich in caffeic acid phenethyl ester (CAPE), has been used since antiquity in Egyptian, Greek, and Roman traditions for wound care and infection control, with records dating to at least the first century CE in Pliny the Elder's writings. Coffee, now one of the world's most consumed beverages and the primary dietary source of chlorogenic acid (caffeic acid ester), was cultivated and consumed in the Arabian Peninsula from the 15th century onward, though its phenolic constituents were not chemically characterized until the 19th and 20th centuries. The systematic isolation and study of caffeic acid as an individual bioactive compound is a product of 20th-century analytical chemistry rather than traditional knowledge.

## Synergistic Combinations

Caffeic acid demonstrates complementary [antioxidant](/ingredients/condition/antioxidant) synergy with other polyphenols such as quercetin and resveratrol, as these compounds target overlapping but mechanistically distinct nodes of the NF-κB and Nrf2 pathways, potentially producing additive [anti-inflammatory](/ingredients/condition/inflammation) effects. Its combination with vitamin C may regenerate the caffeic acid radical back to its active reduced form, extending its antioxidant half-life in biological compartments — a mechanism established for phenolic-ascorbate interactions in the polyphenol literature. In propolis-derived formulations, CAPE (caffeic acid phenethyl ester) co-occurs with flavonoids such as chrysin and pinocembrin, creating a naturally synergistic matrix that may enhance overall anti-inflammatory and [antimicrobial](/ingredients/condition/immune-support) bioactivity beyond isolated caffeic acid.

## Frequently Asked Questions

### What foods are highest in caffeic acid?

Black chokeberries contain approximately 645 mg of caffeic acid per 100 g dry weight, making them among the richest known dietary sources. Coffee is also a major contributor, providing 9–87 mg per 100 g depending on preparation method, and other sources include olives, artichokes, rosemary, and thyme, where caffeic acid occurs primarily as chlorogenic acid or rosmarinic acid ester conjugates.

### How well is caffeic acid absorbed by the body?

Human absorption studies indicate caffeic acid is absorbed with approximately 95 ± 4% efficiency, which is exceptionally high for a dietary polyphenol. Absorption begins passively in the stomach and continues via monocarboxylic acid transporter (MCT)-mediated active transport in the intestines, with plasma concentrations peaking within one hour of ingestion and declining rapidly thereafter.

### Does caffeic acid have anticancer properties?

Preclinical in vitro studies demonstrate that caffeic acid inhibits multiple cancer-related pathways at concentrations of 20–100 µM, including PI3K/Akt, NF-κB/IL-6/STAT3, and VEGF signaling in hepatocellular carcinoma, breast cancer MCF7, and lung cancer H1299 cells. However, these are cell culture findings and no human clinical trials have confirmed anticancer efficacy, so these results cannot currently be translated into therapeutic recommendations.

### Is caffeic acid the same as caffeine?

No — caffeic acid and caffeine are chemically unrelated compounds despite sharing a name prefix derived from coffee (Coffea arabica). Caffeic acid is a hydroxycinnamic acid polyphenol with antioxidant and anti-inflammatory properties, while caffeine is a methylxanthine alkaloid with stimulant effects on the central nervous system through adenosine receptor antagonism.

### Are there any safety concerns or drug interactions with caffeic acid supplements?

Caffeic acid from dietary food sources is considered safe, but isolated high-dose supplementation lacks formal human safety and toxicology data. Theoretical concerns include inhibition of cytochrome P450 enzymes — potentially altering metabolism of certain medications — and iron chelation that could interfere with iron absorption; additive effects with anticoagulants like warfarin are also theoretically possible but unconfirmed in human trials.

### What is the difference between caffeic acid and caffeic acid phenethyl ester (CAPE)?

Caffeic acid phenethyl ester (CAPE) is a derivative where caffeic acid is bonded to phenethyl alcohol, creating a different compound with potentially enhanced bioavailability and biological activity. While caffeic acid is the parent polyphenol found naturally in plants, CAPE is a modified form often used in supplement formulations to improve cellular penetration and anti-inflammatory effects. Both share the same core caffeic acid structure but differ in their absorption profiles and potency in specific tissues.

### How does caffeic acid reduce inflammation in the body?

Caffeic acid reduces inflammation by downregulating pro-inflammatory markers including COX-2, IL-8, MCP-1, and VCAM-1 in endothelial and immune cells, effectively suppressing the inflammatory cascade at the molecular level. This mechanism involves both direct free radical scavenging (with measured DPPH activity of 0.90 ± 0.01 mM Trolox equivalents) and iron-chelating activity (75.80 ± 1.07%), which prevents iron-catalyzed oxidative stress that perpetuates inflammation. The dual antioxidant and anti-inflammatory action makes caffeic acid particularly relevant for conditions driven by chronic oxidative and inflammatory stress.

### Who would benefit most from caffeic acid supplementation?

Individuals with chronic inflammatory conditions (such as cardiovascular disease, arthritis, or inflammatory bowel conditions), elevated oxidative stress markers, or those seeking antioxidant support would likely benefit most from caffeic acid supplementation. People with limited dietary intake of polyphenol-rich foods like coffee, tea, and vegetables may also experience benefits from targeted supplementation. However, those already taking anticoagulant medications or with iron metabolism disorders should consult a healthcare provider before supplementing due to caffeic acid's iron-chelating properties.

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