Home Supplements That Start With D Dicaffeoylquinic Acid: Plant-Based Antioxidant, Health Effects, Dosage & Safety

Dicaffeoylquinic Acid: Plant-Based Antioxidant, Health Effects, Dosage & Safety

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Dicaffeoylquinic acid (diCQA) is a family of plant polyphenols best known as naturally occurring “isochlorogenic acids” in coffee leaves and beans, artichoke, sweet potato leaves, Centella asiatica, and several herbal teas. Each diCQA molecule carries two caffeic-acid groups attached to quinic acid, a structure linked to strong antioxidant and anti-inflammatory actions. Emerging laboratory and animal research suggests potential roles in metabolic health, neuroprotection, and lung inflammation, while human data mostly come from studies on the broader chlorogenic acids (CGAs) group that includes diCQAs. If you already drink coffee or use botanical extracts standardized to chlorogenic acids, you’re likely consuming small amounts of diCQA. This guide explains what diCQA is, how it might work, where to find it, how people typically use it in practice, sensible dosing approaches based on current evidence, and safety considerations to help you make informed decisions.

Essential Insights for Dicaffeoylquinic Acid Users

  • Antioxidant and anti-inflammatory actions may support vascular, metabolic, and brain health.
  • Early evidence links diCQA to glucose and lipid regulation in models; robust human trials are limited.
  • Common supplemental practice: 200–400 mg/day of total chlorogenic acids; actual diCQA content varies by product.
  • Safety caveat: concentrated high-dose diCQA lacks long-term human data; start low and monitor tolerance.
  • Avoid or use medical guidance if pregnant, breastfeeding, or taking diabetes drugs due to potential glucose-lowering effects.

Table of Contents

What is dicaffeoylquinic acid?

Dicaffeoylquinic acids (diCQAs) are members of the chlorogenic acids (CGAs), a broad class of plant phenolics formed when hydroxycinnamic acids such as caffeic acid esterify with quinic acid. In diCQAs, two caffeoyl groups attach at different positions on the quinic acid ring, yielding structural isomers with distinct names and subtle differences in activity. You will often see them labeled by their substitution pattern (for example, 3,5-diCQA, 3,4-diCQA, and 4,5-diCQA) or by historical synonyms: isochlorogenic acid A (3,5-diCQA), B (3,4-diCQA), and C (4,5-diCQA). These isomers co-occur with related mono- (e.g., 5-CQA, “chlorogenic acid”) and tricaffeoylquinic acids in many edible plants.

Where it’s found: Coffee plants are the best-studied source—leaves, unroasted beans, flowers, and by-products contain measurable diCQAs. But diCQAs are not exclusive to coffee. They appear in artichoke (Cynara cardunculus), Centella asiatica, sweet potato leaves (Ipomoea batatas), some thistles and wormwood species, and in certain traditional herbal teas. Because their concentrations vary with plant variety, growing conditions, and processing (roasting, blanching, brewing), the diCQA content of foods and supplements can differ widely even when the label lists the same plant.

How the body handles them: In humans, intact acyl-quinic acids—including diCQAs—are absorbed only to a limited extent in the small intestine. Most reach the colon, where gut microbes hydrolyze them to release caffeic acid and related compounds that are then absorbed, transformed (e.g., to ferulic, isoferulic, and dihydroferulic acids), conjugated (sulfates, glucuronides), and circulated or excreted in urine. This means many of the health effects ascribed to diCQA may arise from these downstream metabolites working systemically, plus local actions in the gut. Inter-individual variability in microbiome composition and transit time helps explain why responses to caffeoylquinates differ from person to person.

How diCQA compares with other CGAs: Adding a second caffeoyl group generally increases radical-scavenging potential and metal-chelating capacity in vitro. Some diCQA isomers show stronger effects on cellular defense pathways (for example, Nrf2 activation) or on enzymes involved in carbohydrate digestion than their mono-caffeoyl counterparts. However, structure–activity relationships are nuanced: the placement of caffeoyl groups (3,4 vs. 3,5 vs. 4,5) can change potency, stability, and how a molecule is metabolized.

Bottom line: diCQA is a naturally occurring subset of chlorogenic acids with promising biological properties, but its real-world effects depend on source, dose, isomer mix, and your microbiome.

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Evidence-backed benefits and how it works

Antioxidant defense and redox signaling
DiCQAs neutralize reactive oxygen species directly and, more importantly, engage the body’s own defense systems. In cell models, diCQA-rich fractions and purified isomers increase the expression of antioxidant enzymes (for example, heme oxygenase-1) via the Nrf2 pathway and reduce markers of oxidative damage. This dual action—scavenging plus signaling—helps protect membranes and mitochondria under stress conditions. Because diCQA and other CGAs are metabolized extensively, their metabolites also contribute to measured antioxidant capacity in blood and tissues.

Anti-inflammatory pathways
In experimental systems, diCQAs dampen pro-inflammatory signaling by curbing NF-κB activation and lowering cytokines such as TNF-α and IL-6. One area of particular interest is the respiratory tract: a recent pharmacological review highlights diCQAs as potential modulators of lung inflammation, citing inhibition of leukocyte infiltration and mitigation of oxidative stress in models of airway injury. Mechanistically, diCQAs appear to interfere with upstream kinases and to preserve epithelial barrier function under oxidative load.

Metabolic effects (glucose and lipids)
Across cells and animal models, diCQAs show several glucose-regulating actions: (1) inhibition of intestinal α-glucosidase and, to a lesser degree, α-amylase, which can slow carbohydrate breakdown; (2) modulation of hepatic glucose output; and (3) indirect effects through altered gut microbial metabolism of polyphenols. In adipocyte models, 3,5-diCQA has been reported to blunt early steps of adipogenesis while upregulating antioxidant defenses. In rodents, diCQA-rich plant extracts have improved insulin sensitivity and lipid profiles alongside reduced inflammatory markers. Translating these findings to humans requires caution, but they align with small human studies on total CGAs showing modest reductions in post-meal glucose excursions.

Cardiovascular and mitochondrial protection
DiCQAs protect cells under oxidative challenge by preserving mitochondrial membrane potential, reducing apoptosis, and improving bioenergetic markers. In cardiomyocyte models, 3,5-diCQA activated the PI3K/Akt survival pathway, lowered Bax/caspase-3 signaling, and rescued cells from tert-butyl hydroperoxide–induced injury. These mechanistic data are preliminary yet consistent with the broader literature on CGAs supporting endothelial function and vascular reactivity.

Neuroprotection and cognitive aging (early-stage)
Dicaffeoylquinates are among the bioactives associated with neuroprotective effects in Centella asiatica and related botanicals. In vitro, specific diCQA isomers protect neurons from amyloid-β toxicity and oxidative stress, potentially via Nrf2-dependent transcription and mitochondrial support. Human cognition trials to date typically use multi-compound extracts rich in various CQAs, so it’s hard to isolate diCQA’s unique contribution; still, the mechanistic rationale is strong enough to merit clinical testing.

Respiratory health focus
A recent review proposes diCQAs as candidate agents for inflammatory airway conditions, integrating evidence of antioxidant, anti-inflammatory, and anti-apoptotic actions in lung tissues and immune cells. While this is not clinical guidance, it’s a clear signal for future trials—especially for plant-based preparations (e.g., coffee-leaf infusions or standardized extracts) where diCQAs are abundant.

Takeaway on efficacy: The most convincing data for diCQA are mechanistic (cells, enzymes) and supportive animal studies, with human-level evidence coming mainly from research on total CGAs. Expect subtle, cumulative effects—especially on post-prandial metabolism and redox balance—rather than drug-like outcomes. Quality, isomer profile, dose, and your microbiome will shape real-world benefits.

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How to use it: sources and forms

Dietary sources
If you drink coffee or consume coffee-leaf or cherry infusions, you’re already ingesting CGAs that include small amounts of diCQA. Unroasted (green) coffee and coffee leaves generally contain a higher proportion of diCQAs than dark-roasted beans because roasting degrades and transforms CGAs. Outside coffee, artichoke leaves, Centella asiatica, and sweet potato leaves are meaningful contributors. Culinary approaches—steeping, blanching, stir-frying—change the extracted profile; water-based preparations tend to favor CGAs, while high heat shifts them toward breakdown products and lactones.

Supplement forms
Most products standardize to “chlorogenic acids” (often 45–70% CGAs in green coffee bean extract) without specifying the diCQA fraction. A few specialized extracts (e.g., artichoke leaf, Centella) may list 1,3-diCQA (cynarin) or “isochlorogenic acids” on spec sheets. Because labeling practices vary, the actual diCQA intake from a given capsule can differ widely—even between lots of the same brand.

Practical ways to incorporate diCQA:

  • Food-first: One to two cups of brewed coffee or tea made from diCQA-rich botanicals contributes small but consistent amounts alongside other polyphenols.
  • Standardized extracts: Choose reputable brands that disclose total CGAs and, when possible, specify diCQA or “isochlorogenic acids.” Third-party testing (certificates of analysis) is a plus.
  • Timing: If you’re using CGA-rich capsules for post-meal glucose support, take them 15–30 minutes before carbohydrate-heavy meals. For individuals sensitive to caffeine, select decaffeinated CGA extracts (caffeine-free does not mean polyphenol-free).
  • Stacking: Pairing CGA/diCQA with fiber (e.g., beta-glucans) or protein may temper glucose spikes through complementary mechanisms. Magnesium and vitamin D repletion can support glucose regulation and endothelial function, but these are adjuncts—not replacements—for diet and activity.

What to look for on labels:

  • Standardization (e.g., “45% chlorogenic acids”), decaffeination status, plant part, extraction solvent (water/ethanol preferred), and batch COA.
  • Sensible serving sizes that align with current practice (often 200–400 mg/day total CGAs split in one or two doses).
  • Transparent cautions for pregnancy, breastfeeding, and medication interactions (especially diabetes drugs).

Storage and stability
DiCQAs are sensitive to heat and prolonged storage in humid conditions. Keep extracts in airtight containers away from light and moisture. With coffee, shorter storage times and whole-bean formats better preserve the native CGA profile.

Bottom line: Most people get diCQA incidentally through diet; supplements can raise total CGA intake, but the exact diCQA dose is rarely specified. Prioritize quality and transparency, start low, and match timing to your goals (e.g., before high-carb meals).

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How much per day? Practical dosage guidance

There is no officially established human dose for purified dicaffeoylquinic acid. Nearly all human-level guidance comes from experience with total chlorogenic acids (CGAs), of which diCQAs are a subset.

What research and practice suggest:

  • Dietary exposure: Coffee is the dominant dietary source of CGAs globally. Depending on bean variety, roast, and brew method, a typical cup can provide a broad range of CGAs; diCQAs generally make up a smaller fraction than mono-caffeoylquinates. Day-to-day intake varies with habits and preparation.
  • Supplemental practice: Many green coffee bean extracts provide 200–400 mg/day of total CGAs, often split into one or two servings. Products sometimes highlight “isochlorogenic acids,” but the actual diCQA milligrams are rarely disclosed and can vary by harvest and lot.
  • Food-based extracts (artichoke, Centella): Labels usually specify extract mass rather than diCQA content. Follow the manufacturer’s instructions and evaluate how you feel over 2–4 weeks.

A stepwise, low-risk approach:

  1. Clarify your goal (e.g., support post-meal glucose).
  2. Pick a quality product with verified CGA content or rely on foods naturally rich in CQAs.
  3. Start at the low end (for supplements, a single daily serving that provides ~200 mg CGAs) and assess tolerance for 1–2 weeks.
  4. If desired and tolerated, increase toward ~300–400 mg CGAs/day. Because diCQA labeling is inconsistent, avoid stacking multiple CGA products unless the combined intake is clear.
  5. Time near meals if targeting post-prandial responses.

Special considerations:

  • Caffeine: Decaf CGA extracts exist; choose them if you’re sensitive.
  • Glycemia: If you take diabetes medications or monitor glucose, track your readings when you introduce or adjust CGA/diCQA intake.
  • Individual variability: Differences in gut microbiota profoundly affect how CGAs and diCQAs are metabolized. Two people taking the same product can have different responses.

What not to do:

  • Don’t assume “more is better.” High, sustained intakes of concentrated diCQA lack long-term human safety data.
  • Don’t replace prescribed therapy with polyphenol supplements.
  • Don’t ignore label caffeine content if taken late in the day (with coffee-derived products).

Bottom line: Sensible daily targets come from total CGA practice (~200–400 mg/day), recognizing that diCQA content is variable and often undisclosed. Keep doses modest, match timing to your purpose, and monitor how you respond.

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Side effects, interactions, and who should avoid it

Overall safety picture
Current toxicological and clinical evidence on chlorogenic acids, including diCQAs, suggests a good safety margin at typical dietary intakes and with moderate supplemental use. Risk assessments of coffee by-products—materials particularly rich in 5-CQA and 3,5-diCQA—have not identified acute toxicity concerns within normal exposure ranges. That said, purified high-dose diCQA has not been extensively tested in humans over the long term.

Possible side effects (usually mild and dose-related):

  • Gastrointestinal: Nausea, stomach upset, or loose stools may occur when starting or increasing CGA-rich extracts. Splitting the dose with food commonly helps.
  • Heartburn: Acid-sensitive individuals may notice reflux with coffee-derived products.
  • Sleep disruption: Only relevant to caffeinated products; choose decaf CGA extracts if needed.

Potential interactions and cautions:

  • Glucose-lowering medications (metformin, sulfonylureas, insulin): Because CGAs can modestly reduce post-meal glucose in some individuals, monitor for additive effects and discuss changes with a clinician.
  • Antihypertensives: CGA-rich diets are generally compatible; still, if you titrate blood-pressure therapy, log readings when adding new supplements.
  • Iron absorption: Polyphenols may reduce non-heme iron uptake when taken with iron-rich plant meals. If you manage iron deficiency, separate CGA supplements from iron by several hours.
  • Allergies: Rare; those with known sensitivity to source plants (e.g., Asteraceae family) should proceed cautiously.

Who should avoid or seek medical guidance first:

  • Pregnant or breastfeeding individuals: Human safety data for concentrated diCQA are lacking.
  • People with diabetes on medication: Introduce slowly with glucose monitoring.
  • Individuals with significant liver or kidney disease: Polyphenol handling and metabolite excretion can be altered—obtain clinical advice.
  • Children: No dosing standards; food sources in normal amounts are generally fine, but supplements are not recommended without pediatric guidance.

Quality and contamination concerns
Choose reputable brands with third-party testing. Coffee-derived ingredients should be screened for contaminants (e.g., mycotoxins, pesticides), and decaffeinated products should state the decaffeination method.

Practical safety tips

  • Start low, go slow, and take with meals if your stomach is sensitive.
  • Keep a brief log of dose, timing, and any symptoms during the first two weeks.
  • Reassess need and benefit periodically rather than using continuously without a goal.

Bottom line: diCQA appears safe within the context of typical CGA intakes, but evidence for high-dose purified diCQA is limited. When in doubt—especially with pregnancy, chronic illness, or medication use—consult a healthcare professional before starting.

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What the research says: strengths and limitations

What’s strong:

  • Chemistry and occurrence are well described. We know the main diCQA isomers, where they occur in plants, and how processing alters them.
  • Mechanistic evidence is robust. DiCQAs exhibit antioxidant, anti-inflammatory, and mitochondria-protective actions across multiple cell types. Examples include activation of Nrf2-dependent genes, inhibition of NF-κB signaling, and cardiomyocyte protection via PI3K/Akt.
  • Safety at dietary levels appears favorable. A recent risk assessment covering chlorogenic and isochlorogenic acids in coffee by-products concluded that both acute and chronic intakes within normal ranges are unlikely to pose health risks.

Where evidence is developing:

  • Pharmacokinetics in humans: The best-available data address total CGAs. They indicate that intact acyl-quinic acids are poorly absorbed in the small intestine; most benefits likely stem from microbial breakdown products and their conjugates. Specific human pharmacokinetics for individual diCQA isomers are sparse.
  • Clinical efficacy: There are few, if any, randomized controlled trials of isolated diCQA in humans. Clinical trials typically use multi-bioactive extracts (e.g., green coffee, artichoke) or whole beverages (coffee), making it hard to attribute outcomes solely to diCQA.
  • Dose–response: Without standardized diCQA supplements and consistent labeling, it’s difficult to establish precise human dose–effect relationships.

Research directions to watch:

  • Respiratory health: Integrative pharmacology points to diCQA as a candidate for lung inflammation and epithelial resilience. Human trials are needed.
  • Microbiome-mediated actions: Since diCQA metabolism depends heavily on gut microbes, stratifying participants by microbiome profiles may reveal responders and non-responders.
  • Comparative isomer biology: Direct comparisons of 3,4-, 3,5-, and 4,5-diCQA in vivo could clarify which isomers drive specific benefits.
  • Standardization: Better product analytics (e.g., specifying “isochlorogenic acids” in mg and isomer ratios) would improve both consumer guidance and research reproducibility.

How to interpret the current state:

  • Treat diCQA as part of a dietary polyphenol pattern rather than a stand-alone cure. Expect incremental, supportive effects that work best alongside a balanced diet, activity, and sleep.
  • Prioritize food-first strategies (coffee, artichoke, leafy greens, herbal teas) and moderate, transparent supplementation when appropriate goals are defined (e.g., post-meal glucose support).
  • Watch for upcoming human trials focusing on standardized diCQA profiles—especially in metabolic and respiratory domains.

Bottom line: The science around diCQA is promising but not yet definitive at the clinical level. Leverage the strengths (dietary sources, CGA-based evidence, good safety at customary intakes) while respecting the limits (few diCQA-specific human trials, unclear ideal dose).

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References

Disclaimer

This article is for educational purposes and does not provide medical advice. Dicaffeoylquinic acid and chlorogenic acid supplements are not intended to diagnose, treat, cure, or prevent disease. Always consult a qualified healthcare professional before starting, stopping, or changing any supplement—especially if you are pregnant or breastfeeding, have a medical condition, or take prescription medications.

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