Quinic Acid: A Comprehensive Encyclopedic Reference
1. Identity and Chemical Characterization
1.1 Names and Classification
Quinic acid is an organic compound with the formula (CHOH)3(CH2)2C(OH)CO2H. The compound is classified as a cyclitol, a cyclic polyol, and a cyclohexanecarboxylic acid. Its IUPAC systematic name is (1R,3R,4R,5R)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid, and it bears the CAS registry number 77-95-2. Chemically, quinic acid is a chiral organic acid with the molecular formula C7H12O6. It is characterized by a cyclohexane ring bearing a carboxylic acid group and multiple hydroxyl groups. Additional common synonyms include 1,3,4,5-tetrahydroxycyclohexanecarboxylic acid and cyclohexanecarboxylic acid (used colloquially). Quinic acid (QA) is a biogenic cyclitol, widely distributed in nature as a secondary metabolite produced via the shikimate pathway.
It is a colorless solid that can be extracted from plant sources. Its common appearance as a refined material is as a white to light yellow crystalline powder, with a typical purity exceeding 98%. Its structure imparts several key properties, including its ability to chelate metal ions and its role as a chiral pool starting material for complex syntheses.
1.2 Biosynthesis and Relationship to the Shikimate Pathway
Its biosynthesis begins with the transformation of glucose into erythrose-4-phosphate. This four-carbon substrate is condensed with phosphoenolpyruvate to give the seven-carbon 3-deoxy-D-arabinoheptulosonate 7-phosphate (DAHP) by the action of a synthase. Two subsequent steps involving dehydroquinic acid synthase and a dehydrogenase afford the compound. Within the shikimate pathway, 3-dehydroquinate is an early carbocyclic intermediate and functional branch point: it can either proceed along the main trunk (via dehydration to 3-dehydroshikimate) or be reduced to QA by quinate/shikimate dehydrogenase. While not a direct precursor of the shikimate main line, many microorganisms can reoxidize QA back to 3-dehydroquinate, providing alternative carbon sources and regulatory links to the biosynthesis of aromatic compounds.
Derived bicyclic lactones of quinic acid are called quinides, with 4-caffeoyl-1,5-quinide being one example. Dehydrogenation and oxidation of quinic acid affords gallic acid.
1.3 Relationship to Chlorogenic Acids
Quinic acid is present in many plants as a caffeoylquinic acid — esters of quinic acid with caffeic acids. Esterified with one unit of caffeic acid it forms chlorogenic acid; esterified with two units of caffeic acid, it forms cynarine. More broadly, chlorogenic acids (CGAs) are esters of quinic acid (QA) and one trans-cinnamic acid residue such as caffeic acid, p-coumaric acid, and ferulic acid, which are known as caffeoylquinic acids (CQAs), p-coumaroylquinic acids (p-CoQAs), and feruloylquinic acids (FQAs). The extended list of chlorogenic acids, which contains approximately 400 compounds, also encompasses several derivatives and isomers of quinic acid, including shikimic acid, its epimers, 4-deoxy-, muco-, methyl-, and butyl-quinic acids esterified with hydroxycinnamic and hydroxybenzoic acids or some of their derivatives.
2. Natural Sources and Distribution
2.1 Plant Sources
Quinic acid is found in Cinchona bark at high concentrations. It is also found in coffee beans and the bark of Eucalyptus globulus. It is a constituent of the tara tannins. Kiwifruit also have a high level of quinic acid (1–2% w/w) as a key component of their flavor. Quinic acid is also found in other plants including sweet potatoes, apples, and peaches. Quinic acid is a cyclohexanecarboxylic acid contained in the extracts of several parts of medicinal plants including Haematocarpus validus, Hypericum empetrifolium, Achillea pseudoaleppica, Rumex nepalensis, Phagnalon saxatile subsp. saxatile, Coffea arabica, Ziziphus lotus L, and Artemisia annua L.
The chlorogenic acid content of green coffee beans can represent up to 10% of the dry matter. The term "chlorogenic acid" in fact encompasses a relatively complex mixture of quinic acid derivatives, including caffeoyl, dicaffeoyl, p-coumaroyl, feruloyl, and caffeoylferuloyl quinic acids. After roasting, the coffee grains contain an even more complex mixture of compounds, of which some are formed by lactones of quinic acids known as quinides or even other isomers formed during the heat treatment.
Quinic acid is also found in the Uncaria tomentosa (Cat's Claw) vine. Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (Cat's Claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB). It is also one of the bioactive components in macrofungi (Coprinus comatus).
2.2 Occurrence in Common Foods
Chlorogenic acids — esters of quinic acid and trans-cinnamic acids — number at least 71 different chemical compounds identified from different plant sources such as fruits, vegetables, coffee beans, tea, apples, artichoke, eggplant, and grapes. Both caffeinated and decaffeinated coffee contain a large amount of chlorogenic acid (70–350 mg per cup of coffee), making it one of the most abundant (poly)phenols in a diet of coffee-consuming populations. Caffeoylquinic acids are also ubiquitous among fruits and vegetables; they are present in pomes (Rosaceae) and drupes (Prunus), berries (Rubus), tropical fruits, Apiaceae, and Brassicaceae vegetables, root vegetables, and seeds.
2.3 Forms and Preparations
QA is generally present in free form or as esters in various plants. It can be made synthetically by hydrolysis of chlorogenic acid. As a commercial ingredient, quinic acid is available as an isolated crystalline powder produced by extraction and purification from plant sources, or synthesized chemically or via microbial fermentation. This acid is a versatile chiral starting material for the synthesis of pharmaceuticals. It is a building block in the synthesis of oseltamivir, which is used to treat influenza A and B. In the dietary supplement context, quinic acid is found in standardized plant extracts — particularly Cat's Claw bark extracts and green coffee bean extracts — as well as isolated quinic acid in capsule and tablet form.
3. Historical Isolation and Traditional Use
3.1 Discovery and Early Chemical History
This substance was isolated for the first time in 1790 by German pharmacist Friedrich Christian Hofmann in Leer from Cinchona. Its transformation into hippuric acid by animal metabolism was studied by German chemist Eduard Lautemann in 1863. By 1863, Lautemann advanced the understanding through structural studies, confirming quinic acid's carboxylic acid nature via experiments on its metabolic conversion to hippuric acid in animals. Quinic acid was therefore among the first natural organic acids to be isolated and chemically characterized from botanical medicines.
3.2 Cinchona: The Primary Historical Source
The bark of Cinchona species (family Rubiaceae), native to the Andean regions of South America, is the plant from which quinic acid was first isolated and in which it occurs at high concentrations. Cinchona bark — known historically as "Peruvian bark" or "Jesuits' bark" — was used for centuries by Indigenous Andean peoples and was introduced to European medicine in the 17th century principally as a remedy for malaria and fevers, due to its alkaloid content (most notably quinine). Quinic acid has previously been isolated from natural sources, including cinchona bark, tobacco leaves, and carrot leaves. Because quinic acid co-occurs in cinchona bark alongside quinine and other cinchona alkaloids, early historical uses of cinchona preparations — including bark decoctions and tinctures — would have delivered quinic acid as part of the complex phytochemical mixture, though quinic acid itself was not distinguished as a separate active component during this period of traditional use.
3.3 Cat's Claw (Uncaria tomentosa): Amazonian Traditional Use
Uncaria tomentosa (Ut) is a Rubiaceae widely used in Peru's traditional medicine. It is mainly known by the vernacular name of Cat's Claw due to its morphological aspects and is found in tropical low mountain forests of Central and South America. A decoction of Ut bark, root, and leaves is used traditionally for different health problems, including arthritis, weakness, viral infections, skin disorders, abscesses, allergies, asthma, cancer, fevers, gastric ulcers, haemorrhages, inflammations, menstrual irregularity, rheumatism, urinary tract inflammation, and wounds. Among the Ashaninka people of Peru, as well as other Amazonian groups including the Aguaruna, Bora, and Cashibo, Cat's Claw has been used as a broad-spectrum botanical medicine for generations, typically prepared as a water decoction of the inner bark. Uncaria tomentosa, commonly known as Una de Gato or Cat's Claw, has been widely used historically as a natural remedy, and is currently present in a number of nutritional formulations to treat a large variety of health disorders.
Modern analytical work subsequently identified quinic acid and quinic acid lactone as among the biologically active constituents of hot water extracts of Cat's Claw. The in vivo bioactive component of such water extracts was identified as quinic acid and quinic acid salts, including quinic acid ammonium salts, and its pharmaceutical use was directed toward enhancing immune, anti-inflammatory, anti-aging, anti-tumor, and DNA repair processes.
3.4 Quinic Acid in Coffee and Tea Traditions
Though not ethnobotanically attributed to quinic acid specifically, the widespread global traditions of drinking coffee and tea ensured that populations across Africa, the Middle East, Asia, and Europe consumed significant quantities of quinic acid esters (chlorogenic acids) on a daily basis, with quinic acid as a principal hydrolysis product in the gut. Preeminent among hydroxycinnamic acids, as far as natural occurrence is concerned, is chlorogenic acid (5-O-caffeoylquinic acid), which is caffeic acid esterified with quinic acid. This dietary exposure has shaped significant modern scientific interest in the metabolic role of quinic acid as a constituent of habitual plant-food diets.
4. Key Constituents, Derivatives, and Active Compounds
4.1 Free Quinic Acid
While traditionally studied as a structural moiety of chlorogenic acids, quinic acid (QA) and synthetic derivatives thereof are becoming more relevant as independent scaffolds with broad therapeutic relevance. Free quinic acid in plant extracts is typically present at lower levels than its esterified forms (the chlorogenic acids), but can accumulate to significant concentrations in specific botanical sources such as Cinchona bark and kiwifruit.
4.2 Quinic Acid Esters (Chlorogenic Acids)
Hydroxycinnamoyl-quinic acids (HCQAs) are polyphenol esters formed of hydroxycinnamic acids and (−)-quinic acid. They are naturally synthesized by plants and some microorganisms. HCQAs are biologically active dietary compounds exhibiting several important therapeutic properties, including antioxidant, antimicrobial, anti-inflammatory, neuroprotective, and other activities. The most pharmacologically studied of these esters is chlorogenic acid (5-caffeoylquinic acid, 5-CQA), which is cleaved in the gut to release free caffeic acid and free quinic acid as metabolic products.
4.3 Quinides (Quinic Acid Lactones)
After roasting, coffee grains contain a complex mixture of compounds, some of which are formed by lactones of quinic acids known as quinides, as well as other isomers formed during heat treatment. Quinides are bicyclic internal lactones derived from quinic acid, which arise particularly during the roasting or thermal processing of coffee. Some of these derivatives show antimicrobial activity, opiate antagonistic activity, anti-inflammatory activity, fungistatic activity, cytostatic activity, and inhibiting activity in the biosynthesis of leukotrienes.
5. Established Mechanisms of Action
5.1 Inhibition of NF-κB Signaling
Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (Cat's Claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB). Quinic acid demonstrated anti-inflammatory and antioxidative properties by inhibiting macrophage activation and reducing ROS through the NF-κB and ERK/MAPK pathways. In the context of intestinal inflammation, quinic acid ameliorated ulcerative colitis through the inhibition of two TLR4-NF-κB and NF-κB-INOS-NO signaling pathways, which results in the reduction of colitis complications, including oxidative stress.
5.2 Nrf2/HO-1 Antioxidant Pathway Activation
Oxidative stress contributes to inflammation via excessive production of reactive oxygen species (ROS), which activate redox-sensitive transcription factors, including NF-κB and activating protein 1 (AP-1) and perpetuate chronic inflammation; this is counterbalanced by antioxidant defense mechanisms such as the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway. Quinic acid's engagement with this antioxidant pathway contributes to its capacity to attenuate oxidative damage in multiple tissue contexts.
5.3 Antibacterial Mechanisms
Beyond its interactions with the dehydroquinate (DHQ) enzyme, QA itself exhibits antibacterial activity through shikimate-independent mechanisms. Gao and coworkers demonstrated that QA inhibits S. aureus growth by disrupting membrane integrity, increasing permeability, inducing hyperpolarization, and decreasing membrane fluidity. QA possesses an important antibacterial effect which could be explained by the fact that this molecule modulates the functions of ribosomes and the synthesis of aminoacyl-tRNAs, modifies the levels of glycerophospholipids and fatty acids, and disrupts the oxidative phosphorylation pathway, thereby causing interference with membrane fluidity.
5.4 Antidiabetic Mechanisms
The antidiabetic activity of quinic acid is achieved by stimulation of insulin secretion via the mobilization of Ca2+ from intracellular reserves and the increase in the NAD(P)H/NAD(P)+ ratio.
5.5 Anticancer Mechanisms
The anticancer effect of quinic acid is through the promotion of apoptosis, inhibition of activator protein 1 (AP-1) and signaling pathways involving protein kinase C (PKC) and certain mitogen-activated protein kinases (MAPKs), resulting in the downregulation of matrix metallopeptidase 9 (MMP-9) expression.
5.6 Anti-biofilm Activity
Quinic acid at sub-minimum inhibitory concentrations (sub-MICs) significantly inhibited extracellular polysaccharide (EPS) secretion in biofilm formation and mature biofilm of Pseudomonas aeruginosa. P. aeruginosa produces three key extracellular polysaccharides as main components of EPS — alginate, Pel, and Psl — which determined the stability of the biofilm structure.
5.7 Gut Microbiota-Mediated Metabolism
Quinic acid is aromatized into benzoic acid by gut microbiota in vivo and then reacts with glycine in the liver and kidney to generate hippuric acid, which enters the blood. A comprehensive study of quinic acid aromatization was conducted in 22 animal species including man. In man and three species of Old World monkeys (rhesus monkey, baboon, and green monkey), (−)-quinic acid was extensively aromatized and excreted in urine as hippuric acid (20–60% of dose). Treating animals with neomycin in doses sufficient to inhibit bacterial growth in the gut microbiota prevented the conversion of administered quinic acid to urinary hippuric acid, and researchers concluded that the aromatization of quinic acid in both man and guinea pig is performed by intestinal bacteria. This gut microbiota-dependent metabolism is therefore a critical factor in the pharmacological activity of quinic acid in humans.
5.8 Gut Microbiota Modulation
Jin et al. found that gut microbiota play an important role in the inhibition of atherosclerosis in ApoE−/− mice by quinic acid. Further studies explored the potential regulatory effects of quinic acid on gut microbiota and investigated the contributions of gut microbiota to the regulation of intestinal inflammation by quinic acid, using in vitro fermentation with the feces of IBD patients, a DSS-induced colitis mice model, and antibiotics-treated pseudo-germ-free colitis mice.
6. Scientific Evidence by Area of Use
Important note on evidence levels: The scientific evidence base for quinic acid as an isolated compound is, at the time of writing, primarily composed of in vitro (cell culture) and in vivo (animal model) studies, with very limited human clinical trial data. The broader evidence base for chlorogenic acids (quinic acid esters) is more developed. The sections below distinguish these evidence levels clearly.
6.1 Anti-inflammatory Effects
Preclinical evidence (animal models): A rat study investigated the therapeutic effect of quinic acid (QA) on acetic acid-induced colitis in male Wistar rats; ulcerative colitis (UC) was induced intrarectally and the protective effects of QA were investigated across doses of 10, 30, 60, and 100 mg/kg. Rats were treated for 5 days and their colon tissues were dissected out at the end. Macroscopic and histopathological examinations were performed, and the expression of inflammatory and apoptotic genes including TLR4, IL-1β, INOS, IL-6, TNF-α, NF-κB, Caspase-3, Caspase-8, Bax, and Bcl-2 was measured.
A separate animal study examined quinic acid in an arthritis model: Quinic acid at various doses (25, 50, and 100 mg/kg) and methotrexate as reference drug were administered in a Freund's complete adjuvant-induced arthritis model, with one group receiving combination treatment. The study measured body weight changes, paw size, arthritic and joint stiffness score, hematological parameters, lipid profile, asymmetric dimethylarginine, homocysteine, oxidative stress, and inflammatory biomarkers. Quinic acid, a naturally occurring compound, exhibits anti-inflammatory and antioxidant potential.
It has also been found that quinic acid can inhibit vascular inflammation and atherosclerosis by inhibiting the MAP kinase and NF-κB signaling pathways and the adhesion ability of vascular cell adhesion molecules.
Human clinical evidence: In a clinical study, oral administration of quinic acid (1,000 mg/day for 60 days) significantly improved DNA repair and lifestyle-induced clinical responses, including skin quality. This represents one of very few published human studies with isolated quinic acid. The overall human clinical evidence base for quinic acid as an isolated compound in inflammation remains sparse; the broader evidence comes from studies of quinic acid-containing plant extracts and chlorogenic acid-rich preparations.
6.2 Antioxidant Activity
Preclinical and mechanistic evidence: Reports suggest that quinic acid, a metabolite of chlorogenic acid, demonstrated strong antibacterial effects on S. aureus and also acts as an antioxidant, anti-aging, anti-inflammatory agent, antidiabetic, radioprotective, anti-neuroinflammatory, antimutagenic, antiviral, and neuroprotective agent. Quinic acid's antioxidant capacity is linked to its polyhydroxyl structure and its capacity to chelate metal ions, imparted by its cyclohexane ring framework bearing multiple hydroxyl groups. The antioxidant potentials on elevating catalase (CAT) and glutathione (GSH), and reducing lipid peroxidation (LPO) levels propose the potential of quinic acid derivatives in ameliorating painful neuropathy.
Evidence strength: Antioxidant activity is well established in vitro and in several animal models, but robust human randomized controlled trial (RCT) data specific to isolated quinic acid are lacking. Most human antioxidant studies have investigated chlorogenic acids (quinic acid esters) rather than quinic acid itself.
6.3 Neuroprotective and Anti-neuroinflammatory Effects
Preclinical evidence: QA protects against glutamate-induced neurotoxicity by reducing oxidative stress and against Aβ-induced neuronal cell death through inflammatory response suppression. QA derivatives also repress ROS production by inhibiting monoamine oxidase activity in neurons and astrocytes.
Quinic acid (QA) and its derivatives possess anti-oxidant and anti-inflammatory properties. Although previous studies had evidenced QA's benefit on the brain, in vivo and in vitro analyses of its anti-oxidant and anti-inflammatory properties in glial cells had not been fully established. A subsequent study investigated QA's rescue effect in lipopolysaccharide (LPS)-induced behavior impairment; orally administering QA restored social impairment and LPS-induced spatial and fear memory.
Evidence strength: Evidence is confined to cell culture and animal studies. There are currently no published human clinical trials investigating quinic acid specifically for neurological conditions. Results are promising but preliminary.
6.4 Antidiabetic and Metabolic Effects
Preclinical evidence: The antidiabetic activity of quinic acid is achieved by stimulation of insulin secretion via the mobilization of Ca2+ from intracellular reserves and the increase in the NAD(P)H/NAD(P)+ ratio. Quinic acid also inhibits glucose glycoxidation, acts as a metal chelator, and reduces cholesterol in the serum of hyperlipidemia models. A study also demonstrated a synergistic effect of quercetin and quinic acid in alleviating structural degeneration in the liver, kidney, and pancreas tissues of streptozotocin (STZ)-induced diabetic rats.
Evidence strength: Antidiabetic effects of quinic acid have been observed in animal models and in vitro. No published human RCTs specifically examining quinic acid for glycemic control are available in the peer-reviewed literature. Some evidence for benefit comes from human studies of chlorogenic acids from coffee, in which quinic acid is a component, but such studies cannot be attributed to quinic acid alone.
6.5 Antimicrobial Effects
In vitro evidence: QA exhibits antibacterial activity through shikimate-independent mechanisms; it inhibits S. aureus growth by disrupting membrane integrity, increasing permeability, inducing hyperpolarization, and decreasing membrane fluidity. Studies on Pseudomonas aeruginosa found that quinic acid at sub-MICs significantly inhibited EPS secretion in biofilm formation and mature biofilm.
QA and its synthetic derivatives exhibit a wide range of biological activities, including antimicrobial, antifungal, antioxidant, anti-inflammatory, and cytotoxic effects.
Evidence strength: Antimicrobial properties of quinic acid are established in vitro. Animal and human clinical studies are lacking for this indication; all evidence is currently preclinical.
6.6 Anticancer and Antiproliferative Effects
Preclinical evidence: Whitehead and coworkers conducted the synthesis of QA-derived analogues, including COTC (2-crotonyloxymethyl-(4R,5R,6R)−4,5,6-trihydroxycyclohex-2-enone), a product with notable anticancer activity, tested against the non-small-cell lung cancer cell line A549. This body of work on QA biological activities includes anti-inflammatory, antibacterial, and anticancer effects, as well as roles in metabolic and immune modulation.
An intriguing avenue for cancer treatment has emerged in the form of enantio-enriched quinic acid, offering a unique perspective on cancer treatment. Chirality plays a role in drug development and in the pharmacological properties of quinic acid (C7H12O6) derivatives. With enantioselective syntheses, quinic acid enantiomers with distinct stereochemistry can be developed, leading to different biological interactions. Particular enantiomers have been identified that exhibit increased bioactivity while minimizing off-target effects.
Evidence strength: All anticancer evidence for quinic acid and its derivatives is currently at the preclinical stage (in vitro cell culture and animal models). No human clinical trials of quinic acid for cancer treatment have been published. This area is regarded as drug discovery research rather than a clinically validated use.
6.7 Gut and Gastrointestinal Health
Preclinical evidence: Studies explored the potential regulatory effects of quinic acid on gut microbiota and investigated the contributions of gut microbiota to the regulation of intestinal inflammation by quinic acid, using in vitro fermentation with the feces of IBD patients, a DSS-induced colitis mice model, and antibiotics-treated pseudo-germ-free colitis mice.
The therapeutic effect of quinic acid (QA) on acetic acid-induced colitis in male Wistar rats was investigated. Ulcerative colitis (UC) was induced by acetic acid intrarectally, and the protective effects of QA were examined across doses of 10, 30, 60, and 100 mg/kg.
Evidence strength: Evidence is confined to in vitro and animal studies. Human studies are absent for this indication specifically with isolated quinic acid.
6.8 Cardiovascular and Atherosclerosis-Related Effects
Mechanistic and preclinical evidence: Hwang and coworkers reported the analysis of the metabolic profile of human atherosclerotic plaques, finding elevated levels of QA in plaques compared to normal aortic tissue. Consistent with prior studies, QA demonstrated anti-inflammatory and antioxidative properties by inhibiting macrophage activation and reducing ROS through the NF-κB and ERK/MAPK pathways. These findings suggest QA may play a protective role in mitigating inflammation and oxidative stress in atherosclerosis.
Evidence strength: The cardiovascular evidence for quinic acid specifically is very limited and preliminary, derived from metabolomics observations and preclinical experiments. No prospective human clinical trials have investigated quinic acid for cardiovascular disease prevention or treatment.
6.9 DNA Repair and Radioprotection
Quinic acid has the radioprotective, antidiabetic, anti-neuroinflammatory, and antioxidant activities. In a clinical study, oral administration of quinic acid (1,000 mg/day for 60 days) significantly improved DNA repair and lifestyle-induced clinical responses, including skin quality. This human study is among the most direct clinical evidence for isolated quinic acid and appears to have been conducted in the context of the Cat's Claw research program (the "Pero" extract). The evidence in this area, while including some human data, remains limited to a small number of studies.
7. Pharmacokinetics and Metabolism in Humans
7.1 Absorption and Distribution
No apparent degradation of quinic acid was found under either in vitro or in vivo conditions within 24 hours, reflecting that quinic acid is relatively stable under physiological pH and enzymatic conditions.
7.2 Gut Microbial Aromatization and Hippuric Acid Production
The primary metabolic fate of orally ingested quinic acid in humans is its conversion to hippuric acid via a microbially mediated aromatization process in the gut. A comprehensive study of quinic acid aromatization conducted in 22 animal species including man found that in man and three species of Old World monkeys, (−)-quinic acid was extensively aromatized and excreted in urine as hippuric acid (20–60% of the administered dose). In other species, including New World monkeys, lemurs, dog, cat, ferret, rabbit, rat, mouse, guinea pig, hamster, lemming, fruit bat, hedgehog, and pigeon, oral (−)-quinic acid was not extensively aromatized (0–5%). Neomycin pretreatment suppressed hippuric acid (HA) excretion in rhesus monkeys fed (−)-quinic acid.
This species-specific pattern means that the extensive aromatization of quinic acid to hippuric acid is unique to humans and Old World primates and is dependent on intact intestinal microbiota. Quinic acid is aromatized into benzoic acid by gut microbiota in vivo and then reacts with glycine in the liver and kidney to generate hippuric acid, which enters the blood.
7.3 Gastrointestinal Tolerability
In testing of the toxicity of quinic acid (0 to 1,000 µg/mL) against GES-1 (human gastric mucosal cell line) and Caco-2 (human intestinal cell line), no significant influence was observed, reflecting that the doses of quinic acid were almost nontoxic to the epithelial cells of the gastrointestinal tract, making oral administration feasible. Similarly, the nontoxicity of quinic acid against HFF (human foreskin fibroblast) and THP-1 (human monocyte) cells indicated the possibility of dermal topical administration.
8. Dosage Forms and Doses Reported in Studies
Quinic acid as an isolated compound has been tested in a range of forms and doses across preclinical and the limited clinical literature:
- In vitro studies: Concentrations of 0 to 1,000 µg/mL have been used in cell culture experiments assessing cytotoxicity.
- Animal (rat) arthritis model: Quinic acid at various doses (25, 50, and 100 mg/kg body weight) and methotrexate as reference drug were administered, with one group receiving combination treatment.
- Animal (rat) ulcerative colitis model: The protective effects of QA in 10, 30, 60, and 100 mg/kg doses were investigated in rats treated for 5 days.
- Human clinical study (DNA repair and skin quality): Oral administration of quinic acid at 1,000 mg/day for 60 days was reported to significantly improve DNA repair and lifestyle-induced clinical responses, including skin quality.
It is important to note that no standardized or regulatory-approved dosage for quinic acid as a dietary supplement has been established by bodies such as the NIH Office of Dietary Supplements or the European Food Safety Authority (EFSA). Doses reported in the literature are derived from individual research studies and cannot be generalized as established clinical recommendations.
9. Body Systems and Health Areas Associated with Quinic Acid
Currently, in vitro and in vivo pharmacological studies show that quinic acid exhibits various biological activities, such as antioxidant, antidiabetic, anticancer activity, antimicrobial, antiviral, aging protective, anti-nociceptive, and analgesic effects. The body systems and health domains with which quinic acid research has been associated include:
- Immune and inflammatory system: Inhibition of NF-κB, reduction of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), effects in arthritis and colitis models.
- Nervous system: Neuroprotective effects have been elucidated in previous in vitro studies, including protection against glutamate-induced neurotoxicity by reducing oxidative stress and Aβ-induced neuronal cell death through inflammatory response suppression.
- Metabolic and endocrine system: Stimulation of insulin secretion, inhibition of glucose glycoxidation.
- Gastrointestinal system: Anti-colitis activity via TLR4-NF-κB pathway inhibition; gut microbiota modulation.
- Cardiovascular system: Reduction of atherosclerosis-related inflammation through MAPK and NF-κB pathway inhibition.
- Skin and connective tissue: Reported improvement in skin quality and DNA repair in the single human clinical study at 1,000 mg/day.
- Antimicrobial defense: Direct antibacterial activity against organisms including S. aureus and P. aeruginosa; anti-biofilm properties.
10. Role as a Pharmaceutical Precursor
Beyond its role as a dietary supplement and natural product, quinic acid has substantial industrial significance as a chiral building block for pharmaceutical synthesis. This acid is a versatile chiral starting material for the synthesis of pharmaceuticals, and it is a building block in the synthesis of oseltamivir, which is used to treat influenza A and B. Quinic acid is an important molecule utilized as an enantiomerically pure starting material for the synthesis of various biologically important molecules; for example, it is a useful starting material for the synthesis of FK-506, an immunosuppressive agent useful in preventing organ transplant rejection. Additionally, quinic acid has been utilized in the synthesis of the neuraminidase inhibitor GS-4104 (oseltamivir phosphate), an important pharmaceutical for the treatment of influenza. Quinic acid is also utilized as a food additive, a resolving agent, and is being used experimentally in optical materials.
11. Safety Considerations
11.1 Cellular and Animal Toxicity
In toxicity testing of quinic acid at concentrations of 0 to 1,000 µg/mL against human gastric mucosal (GES-1) and intestinal (Caco-2) cell lines, no significant cytotoxic influence was observed, indicating that these doses are almost nontoxic to the epithelial cells of the gastrointestinal tract. Cell line studies against human foreskin fibroblasts and monocytes similarly showed no toxicity, suggesting a favorable preliminary cytotoxic profile.
11.2 Metabolic Considerations: Hippuric Acid Production
A comprehensive study of quinic acid aromatization in 22 animal species, including man, found that in humans, (−)-quinic acid was extensively aromatized and excreted as hippuric acid, representing 20–60% of the administered dose. This metabolic pathway is entirely dependent on intestinal microbiota: pretreatment with neomycin in doses sufficient to inhibit bacterial growth in the gut microbiota prevented the conversion of administered quinic acid to urinary hippuric acid, confirming that the aromatization of quinic acid in humans is performed by intestinal bacteria. The implications for individuals with substantially altered gut microbiota (e.g., from antibiotic therapy or intestinal diseases) are not fully characterized in published studies.
11.3 Relationship to Shikimic Acid and Pharmaceutical Chemistry
Quinic acid is closely related structurally to shikimic acid, which shares similar metabolic pathways. Both compounds are intermediates in the shikimate pathway and both are aromatized to hippuric acid via benzoate by the gut microbiota in humans and Old World primates. The shikimate pathway, of which quinic acid is a side product, is absent in mammals and therefore targeted by certain herbicides and antimicrobials, which do not affect quinic acid metabolism in humans.
11.4 Absence of Formal Regulatory Safety Assessment
Quinic acid as an isolated dietary supplement ingredient has not been the subject of a formal safety monograph from major regulatory bodies such as the NIH Office of Dietary Supplements, EFSA, the European Medicines Agency (EMA), or the WHO at the time of this writing. No established tolerable upper intake level (UL) has been published. The single reported human dose in a published clinical study was 1,000 mg/day for 60 days, with no reported adverse effects in that study, but this constitutes limited evidence from a single trial. Comprehensive dose-escalation safety trials in humans have not been published in the peer-reviewed literature.
11.5 Antibiotic and Gut Microbiota Interactions
The extensive gut-microbial aromatization of quinic acid to benzoic acid and then hippuric acid in humans implies a pharmacokinetically relevant interaction with antibiotic therapy: broad-spectrum antibiotics that disrupt intestinal microbiota are likely to substantially alter the metabolic fate of orally ingested quinic acid. Neomycin pretreatment suppressed hippuric acid excretion in rhesus monkeys fed (−)-quinic acid. The consequences of this interaction for the pharmacological activity of quinic acid are not yet fully understood from published human data.
11.6 Metal Chelation
The structure of quinic acid imparts its ability to chelate metal ions. Quinic acid acts as a metal chelator. The chelation of metal ions may be relevant in the context of concurrent use with mineral supplements or medications requiring metallic cofactors, though the clinical significance of this in the context of typical dietary or supplemental quinic acid exposure has not been formally evaluated in published human studies.
References
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