Shikimic acid

Shikimic Acid: A Comprehensive Reference

1. Identity and Chemical Characterization

Nomenclature and Structure

Shikimic acid (3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid) is a natural organic compound that serves as an important intermediate in the biosynthesis of lignin, aromatic amino acids (phenylalanine, tyrosine, and tryptophan), and most alkaloids of plants and microorganisms. More commonly encountered as its anionic form, shikimate, it is classified simultaneously as a cyclohexene, a cyclitol, and a cyclohexanecarboxylic acid. Composed solely of carbon, hydrogen, and oxygen, shikimic acid functions as an important starting ingredient in several multi-step biochemical manufacturing processes found in a wide range of lifeforms, from bacteria and fungi to parasites and plants.

The molecule possesses a chiral cyclohexene ring bearing three hydroxyl groups and one carboxylic acid group. It naturally occurs in its levorotatory (−) enantiomeric form, commonly designated (−)-shikimic acid or l-shikimic acid, with the full IUPAC stereodescriptor (3R,4S,5R)-3,4,5-trihydroxycyclohex-1-ene-1-carboxylic acid. It is classified as a hydroaromatic compound.

Discovery and Historical Identification

The name "shikimic acid" derives from the Japanese word shikimi (シキミ), referring to the Japanese star anise (Illicium anisatum), from which it was first isolated in 1885 by the Dutch chemist Johan Fredrik Eykman. The full elucidation of its molecular structure was achieved nearly 50 years later. Eykman first purified the compound from the Japanese star anise, a plant known as shikimi in Japan.

2. Natural Sources and Distribution

Primary Botanical Sources

Much of the current global supply of shikimic acid is sourced from the seeds of Chinese star anise (Illicium verum). Only two plant species are found to accumulate this polyhydroxy aromatic acid in commercially relevant amounts: the seeds of Chinese star anise (Illicium verum, family Illiciaceae) and the sweetgum tree (Liquidambar styraciflua). Although there are 42 species of the genus Illicium found in nature, only I. verum is useful for shikimic acid production, yielding up to 7% w/w. The Chinese star anise plant contains between 2 and 7% of shikimic acid in the seed.

Illicium verum (Chinese star anise) is the predominant source, with significant quantities also present in sweetgum fruit (Liquidambar styraciflua), pine needles (Pinus spp.), and various other plant species. I. verum is an aromatic evergreen tree of the family Illiciaceae. It is sometimes contaminated with highly toxic Japanese star anise (I. anisatum L.) and poisonous star anise (I. lanceolatum A. C. Smith), which contain several neurotoxic sesquiterpenes.

Ubiquity in Plants and Microorganisms

Shikimic acid is a natural compound that is a key intermediate in the biosynthesis of amino acids, and consequently this derivative is widely present in many plants and has interesting biological properties. The shikimate pathway is widely distributed in microorganisms and plants, where shikimic acid is a precursor for the biosynthesis of primary metabolites such as aromatic amino acids and folic acid, as well as a great many other aromatic compounds. Since the basic element of all aromatic compounds—the benzene ring—is formed in plants and microorganisms through the shikimate pathway, shikimic acid is an extremely essential compound in plants and microbes.

Commercial Production Methods

Shikimic acid can be produced via chemical synthesis, microbial fermentation, and extraction from certain plants. An alternative production route is via biotransformation of the more readily available quinic acid. Supply from star anise seeds has experienced difficulties and is susceptible to vagaries of weather. The star anise tree takes around six years from planting to bear fruit but remains productive for a long period. Extraction and purification from seeds are expensive. Production via fermentation is increasing.

Shikimic acid is used as a chiral precursor for organic synthesis of oseltamivir (Tamiflu®). The process of microbial production of SA has recently undergone vigorous development. Particularly, the sustainable construction of recombinant Corynebacterium glutamicum (yielding 141.2 g/L) and Escherichia coli (87 g/L) has laid a solid foundation for the microbial fermentation production of SA. Shikimic acid can only be retrieved from plants after 6 years of crop growth and is harvested in September and October. To recover SA from the seed, a 10-step process is required, taking approximately 30 kg of seed to produce 1 kg of SA.

3. Traditional and Historical Use

Traditional Chinese Medicine

Star anise has been used in China for more than a thousand years. The Chinese Pharmacopoeia (2005 edition) documented the main effects of star anise as warming Yang and dispersing cold, regulating Qi and relieving pain. In traditional Chinese medicine, I. verum not only has the functions of warming Yang, dispersing cold, regulating Qi, and relieving pain, but can also be used as a condiment to increase flavor as well as to reconcile and remove fish smells.

In traditional Chinese medicine, star anise has long been used as a digestive aid and warming herb, valued for its supposed ability to regulate chi, or life force. It is one of the first traditional Chinese medicines announced by the Ministry of Health of the People's Republic of China in 2002 for dual use in medicines and foodstuffs. As a well-known spice, star anise was first introduced to Europe in the seventeenth century, and it gets its distinctive licorice taste from the presence of star anise essential oil.

Other Traditional Systems

Traditional uses of I. verum are recorded throughout Asia and Northern America, where it has been used for more than 10 types of disorders. Shikimic acid, as one of the key active constituents, is understood to contribute to many of these traditional applications. Numerous compounds including volatiles, seco-prezizaane-type sesquiterpenes, phenylpropanoids, lignans, flavonoids, and other constituents have been identified from I. verum.

Currently, 201 chemical constituents have been identified from star anise; among these, star anise oil and shikimic acid are the two most widely used and studied chemical components in star anise, with the oil accounting for a large proportion of the total. The traditional preparation most relevant to shikimic acid extraction is the decoction: hot-water preparations efficiently extract the compound, as research has confirmed that a hot water extraction at or above 70°C can recover the majority of shikimic acid present in the plant material.

4. Key Constituents, Biochemistry, and the Shikimate Pathway

Role as a Pathway Intermediate

Three enzymatic reactions convert 3-deoxy-D-arabinoheptulosonate-7-phosphate (DAHP) into shikimate, after which the pathway is named. The next three enzymatic reactions then convert shikimate to chorismate, the last common precursor to all three aromatic amino acids and precursor to salicylic acid. This central metabolic role means shikimic acid acts as a junction point between central carbon metabolism and the synthesis of an enormous diversity of plant secondary metabolites, including flavonoids, tannins, lignins, and alkaloids.

Shikimic acid is generally utilized as a starting material for industrial synthesis of the antiviral oseltamivir, a drug against the H5N1 influenza virus administered to treat and prevent all known strains of influenza virus. Shikimic acid is the precursor for the chemical synthesis of oseltamivir phosphate (OSF), known as Tamiflu®, used as the antiviral inhibitor of the neuraminidase enzyme for the treatment of diverse seasonal influenza viruses, including influenza A and B, the avian influenza virus H5N1, and the human influenza virus H1N1.

Relationship to Oseltamivir (Tamiflu)

Besides the pharmacological relevance of shikimic acid itself, it is also an intermediate in the synthesis of many drugs, with the most relevant being the antiviral agent oseltamivir (Tamiflu™). Until 2012, when Roche Pharmaceuticals switched to using genetically modified E. coli, they used up to 90% of the world's annual star anise crop to produce oseltamivir (Tamiflu) via shikimic acid. It is critically important to note that shikimic acid itself is not oseltamivir. It is a precursor that undergoes extensive multi-step chemical modification to yield the pharmaceutical drug; the pharmacological properties of the finished drug cannot be attributed to shikimic acid directly.

Phytochemical Context of Illicium verum

Star anise contains numerous other bioactive constituents alongside shikimic acid. Along with anethole and shikimic acid, star anise is known to contain linalool, caryophyllene, limonene, gallic acid, and quercetin. These co-occurring compounds may contribute to many of the biological activities attributed to whole-plant preparations, making it difficult to isolate the contribution of shikimic acid alone from studies conducted with crude star anise extracts.

5. Mechanisms of Action

Anti-Inflammatory Mechanisms

Shikimic acid is present in a wide variety of plants and microorganisms used in traditional and folk medicine. Some pharmacological actions observed in SA-enriched products include antioxidant and anti-inflammatory activities. Investigations have been conducted into the anti-inflammatory and antinociceptive actions of isolated SA; RAW 264.7 macrophage cells were treated with bacterial LPS (1 μg/mL) and the effect of SA on the modulation of cell viability, nitric oxide (NO) production, TNF-α, IL-1β content, and MAPK (ERK1/2 and p38) activation was evaluated.

SA inhibits production of pro-inflammatory mediators and reactive oxygen species (ROS) in LPS-induced BV2 microglial cells. Mechanistic studies demonstrated that SA suppresses neuroinflammation by activating the AKT/Nrf2 pathway and inhibiting the NF-κB pathway. Further in vivo studies confirmed that SA ameliorated neurological damage and behavioral deficits caused by LPS injection in mice.

Intragastric administration of SA in a DSS-induced mouse colitis model slowed weight loss, reduced disease activity index (DAI) score, enhanced the intestinal barrier, reduced the destruction of the colonic structure, inhibited the phosphorylation of key proteins in MAPK and NF-κB signaling pathways, and inhibited the expression of inflammatory factors TNF-α, IL-1β, and MPO.

Antioxidant Mechanisms

In vitro antioxidant activity of SA has been demonstrated without exerting cytotoxic effects on SH-SY5Y human neuronal-like cells at tested concentrations. In an animal model of doxorubicin-induced cardiotoxicity, the impact of SA treatment against cardiac deterioration was found to operate through targeting the Nrf2/Keap-1/HO-1/NQO-1 signaling pathway, which in turn induces antioxidant defenses.

Antithrombotic and Antiplatelet Mechanisms

Adenosine diphosphate (ADP) stimulates the P2Y1/P2Y12 pathway of platelet activation to mimic the in vivo thrombogenic pathway. Platelet aggregation studies utilized both ADP and collagen as exogenous platelet agonists to target both P2Y1/P2Y12 and GPVI pathways of thrombus formation. Flow cytometry studies found that SA produced a significant antiplatelet effect on PAC-1 (p = 0.03 at 2 mM) and CD62P (p = 0.017, p = 0.036 at 1 mM and 2 mM respectively) expression, in addition to lowering monocyte-platelet aggregate formation. SA at 1 mM concentration reduced PECAM-1 expression (p = 0.035), signifying a reduction in endothelial leucocyte migration during thrombus growth. SA did not demonstrate a platelet aggregation inhibitory effect by targeting the GPVI collagen pathway but reduced ADP-induced platelet aggregation at 2 mM concentration.

Hypolipidemic Mechanisms

Shikimic acid showed weak cytotoxicity in HepG2, Huh7, and 3T3-L1 cells, but suppressed lipid accumulation in those cell lines by Oil Red O staining. SA attenuated the mRNA expression of de novo lipogenesis-related genes such as FAS, SREBP-1c, and LXR-α in HepG2 cells, and suppressed the protein expression of SREBP-1c and LXR-α. Recent studies have shown that shikimic acid, as a precursor to phenylalanine and other aromatic metabolites, may influence the AMP-activated protein kinase (AMPK) signaling pathway. Activation of AMPK is known to suppress fatty acid synthesis and enhance hepatic fatty acid oxidation, ultimately resulting in lowered serum triglyceride levels. Shikimic acid has been reported to exert a hypolipogenic effect in HepG2 and 3T3-L1 cells by promoting the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), while downregulating MID1IP1.

6. Scientific Evidence by Area of Activity

Important general caveat: The overwhelming majority of evidence for shikimic acid as a direct bioactive agent comes from in vitro cell-culture studies and in vivo animal models. Controlled clinical trials in humans are largely absent across all areas described below. The evidence base should therefore be characterized as preliminary to moderate at best, and no established human therapeutic applications exist for isolated shikimic acid as a supplement.

6.1 Anti-Inflammatory and Analgesic Activity

Several in vitro and in vivo studies indicate that shikimic acid and its derivatives exhibit diverse bioactivities, including anti-inflammatory activity. The most mechanistically detailed work uses LPS-stimulated macrophage and microglial cell models. Investigations into the anti-inflammatory and antinociceptive actions of isolated SA used RAW 264.7 macrophage cells treated with bacterial LPS and evaluated effects on cell viability, nitric oxide (NO) production, TNF-α and IL-1β content, and MAPK (ERK1/2 and p38) activation. The anti-hyperalgesic actions of SA on in vivo models of mechanical hyperalgesia induced by carrageenan, dopamine, TNF-α, and prostaglandin (PGE2) were also assessed. Evidence is at the preclinical stage (in vitro and animal models); no controlled human clinical trials have specifically evaluated shikimic acid supplementation for inflammatory outcomes.

6.2 Antithrombotic and Cardiovascular Activity

An ex vivo study was performed to evaluate the anti-platelet and anti-thrombogenic potential of shikimic acid as a plant phenolic metabolite. Fasting blood samples were collected from 22 sedentary participants to analyse the effect of varying concentrations of SA. The concentrations tested were 0.1 mM, 0.2 mM, 0.5 mM, 1 mM, and 2 mM, examining their effects on platelet surface-marker expression, platelet aggregation, and biomarkers of thrombogenesis. The key finding was a concentration-dependent antiplatelet effect mediated primarily through the P2Y1/P2Y12-ADP pathway. This is the most direct human-tissue evidence available for any activity of isolated shikimic acid, though an ex vivo study with a small sample (n = 22) and pharmacological concentrations applied to blood outside the body should not be equated with a human clinical intervention.

In animal models, triacetylshikimic acid (TSA), an acetylate derivative of shikimic acid, was evaluated for anti-platelet activity and anti-thrombotic efficacy. After oral pretreatment with TSA, ADP-, collagen-, and arachidonic acid-induced rat platelet aggregation was inhibited ex vivo in a dose-dependent manner. In a rat model of doxorubicin-induced cardiotoxicity, SA treatment led to significant amelioration of cardiotoxicity by restoring hematological, biochemical, inflammatory biomarkers, antioxidant gene expression, and cardiac histopathological alterations; the mechanism targets the Nrf2/Keap-1/HO-1/NQO-1 signaling pathway. These findings suggest SA treatment could potentially mitigate cardiac toxicity during doxorubicin-based chemotherapy.

6.3 Antiviral Activity

Shikimic acid has been thrust under the spotlight in recent years because it is generally used as a starting material for the industrial synthesis of the antiviral oseltamivir, a drug against the H5N1 influenza virus. However, the antiviral activity of oseltamivir is a property of the fully synthesized pharmaceutical drug, not of shikimic acid itself. The contribution of shikimic acid per se to antiviral activity against influenza or other viruses, taken orally as a supplement, has not been established in rigorous clinical studies.

Regarding other viruses, a study aimed to evaluate the antiviral effects of shikimic acid against Chikungunya virus (CHIKV) through network pharmacology, molecular docking, and in vitro assays. Network pharmacology analysis identified 26 potential targets through which SA could inhibit CHIKV, including key pathogenic targets such as TNF, IL-6, and MAPK3. This hypothesis was further supported by molecular docking. The molecular docking analysis revealed that SA could interact with multiple CHIKV-related targets, with vina scores generally lower than −6, indicating a high propensity for stable complex formation. Although the precise anti-CHIKV activity of SA has yet to be definitively established, its broad range of biological activities makes it a candidate of interest. This work is computational and in vitro; no human antiviral trials for shikimic acid exist.

6.4 Neuroprotective Activity

Researchers evaluated the thermoanalytical profile, redox properties, and in vitro effects of SA on human neuronal-like cells (SH-SY5Y). Results showed in vitro antioxidant activity of SA without exerting cytotoxic effects on SH-SY5Y cells at tested concentrations of 10 nM, 10 μM, and 10 mM. The neuroprotective effect of SA has been investigated against hydrogen peroxide-induced oxidative stress on human neuronal-like cells (SH-SY5Y).

In an in vivo model relevant to Parkinson's disease, numerous studies have shown that neuroinflammation is involved in the process of neuronal damage in neurodegenerative diseases such as Parkinson's disease (PD). Shikimic acid has anti-inflammatory, analgesic, and antioxidant activities in numerous diseases. SA inhibits production of pro-inflammatory mediators and ROS in LPS-induced BV2 cells. Mechanistic studies demonstrated that SA suppresses neuroinflammation by activating the AKT/Nrf2 pathway and inhibiting the NF-κB pathway. In vivo studies confirmed that SA ameliorated neurological damage and behavioral deficits caused by LPS injection in mice. These studies highlighted the beneficial role of SA as a potential novel therapy for PD targeting neuroinflammation. All evidence remains at the preclinical stage.

6.5 Hypolipidemic Activity

Evidence for lipid-lowering effects derives from cell culture and animal work. Shikimic acid suppressed lipid accumulation in HepG2, Huh7, and 3T3-L1 cells and attenuated the mRNA expression of de novo lipogenesis-related genes such as FAS, SREBP-1c, and LXR-α in HepG2 cells, and suppressed the protein expression of SREBP-1c and LXR-α.

In a 28-day murine toxicity/dietary study, a significant reduction in triglyceride levels was observed in the high-dose group (50 g/kg diet), suggesting potential hypolipidemic effects for shikimic acid. A significant reduction in serum triglyceride (TG) levels was observed in the high-dose group (P < 0.001), and these findings indicate that shikimic acid may exert lipid-lowering effects, warranting further investigation into its hypolipidemic potential. No human clinical trials assessing lipid outcomes have been published.

6.6 Gastrointestinal and Gut Microbiota Effects

A DSS-induced mouse colitis model was used to investigate the effects of SA on intestinal inflammation. Intragastric administration of SA slowed DSS-induced weight loss, reduced disease activity index (DAI) score, enhanced the intestinal barrier, reduced the destruction of the colonic structure, inhibited the phosphorylation of key proteins in MAPK and NF-κB signaling pathways, and inhibited the expression of inflammatory factors TNF-α, IL-1β, and MPO. The authors also found modulatory effects on gut microbiota composition in the murine model. This is entirely preclinical evidence.

6.7 Hepatoprotective Activity

Shikimic acid is predominantly found in star anise (Illicium verum). Its pharmacological derivatives possess a wide range of bioactivities, including antioxidant, antiviral, anti-inflammatory, and antibacterial properties, combined with low toxicity, making them promising candidates for therapeutic applications across various organ systems. In a 2025 preclinical study, shikimic acid was investigated in a thioacetamide (TAA)-induced hepatic fibrosis model in rats, with findings suggesting protective effects mediated via Nrf2/NF-κB signaling pathways. All hepatoprotective evidence remains animal-based.

6.8 Renoprotective Activity

One study aimed to assess the renoprotective effect of Artemisia absinthium extract and its bioactive compound, shikimic acid, against cisplatin-induced renal injury. An in vitro assay was performed in kidney tubular epithelial cells (LLC-PK1) with 25 and 50 µM shikimic acid, and BALB/c mice were orally administered 25 and 50 mg/kg shikimic acid daily for 4 days following cisplatin injection. Shikimic acid reversed the effect on cell viability and decreased oxidative stress and apoptosis in renal cells compared with levels in the cisplatin-treated group. This is preclinical evidence only.

6.9 Bone-Protective and Osteoarthritic Effects

Several in vitro and in vivo studies indicate that shikimic acid and its derivatives exhibit bone-protective activity. Published work has investigated shikimic acid's effects in osteoarthritis models, with reported mechanisms involving restoration of impaired autophagy and suppression of the MAPK/NF-κB signaling pathway in chondrocytes. All such evidence is from preclinical models.

6.10 Antibacterial Activity

Shikimic acid is a hydroaromatic compound possessing critical biological properties including antibacterial activity. The antibacterial properties have been demonstrated primarily in vitro, against various bacterial strains. Because the shikimate pathway itself is absent in humans and other animals but present in many bacteria and fungi, shikimic acid and its derivatives have attracted interest as potential antimicrobial scaffolds. However, clinical antimicrobial applications of shikimic acid itself remain undeveloped.

7. Body Systems and Health Areas of Association

Various in vitro and in vivo investigations have shown that shikimic acid and its derivatives have various bioactivities including antioxidant, antiviral, and anticancer properties; anti-inflammatory effects (decreases in cell viability, TNF-α, nitrite production, and IL-1β); antibacterial, hypolipidemic, bone-protective, skin-protective, neuroprotective (e.g., blocking mechanical hyperalgesia), and antidiabetic activities.

• Cardiovascular system: Antithrombotic and antiplatelet effects; potential cardioprotection against oxidative/toxic injury
• Nervous system: Neuroprotection through antioxidant and anti-neuroinflammatory mechanisms (preclinical)
• Gastrointestinal tract: Anti-colitis effects; modulation of gut microbiota composition (preclinical)
• Liver: Hepatoprotection against fibrotic and toxic injury via Nrf2/NF-κB pathways (preclinical)
• Kidney: Renoprotection against cisplatin-induced injury (preclinical)
• Immune system: Modulation of macrophage-mediated inflammation; inhibition of pro-inflammatory cytokine production
• Musculoskeletal system: Bone-protective and chondroprotective effects (preclinical)
• Metabolic system: Potential antidiabetic and hypolipidemic effects (preclinical)
• Skin: Potential skin-protective and exfoliating effects (largely from in vitro or topical-application-based evidence)

8. Dosage Forms and Reported Dosages

There is no established human therapeutic dose for shikimic acid as a dietary supplement. The following dosages appear only in the cited preclinical and ex vivo studies and are presented solely as reported by those sources.

• Ex vivo human platelet study: Fasting blood samples from 22 sedentary participants were analyzed for the effect of varying concentrations of SA: 0.1 mM, 0.2 mM, 0.5 mM, 1 mM, and 2 mM. These are pharmacological concentrations applied directly to blood ex vivo, not oral doses.
• Mouse renoprotection study: BALB/c mice were orally administered 25 and 50 mg/kg shikimic acid daily for 4 days.
• Murine subchronic toxicity study: In a 28-day subchronic oral toxicity study, mice fed diets containing high (50 g/kg diet), medium (16.67 g/kg diet), or low (5.56 g/kg diet) doses of shikimic acid exhibited no mortality. The pharmacokinetic properties and long-term safety profile of shikimic acid in humans remain inadequately characterized.
• Rat cardioprotection study: Animals were gavaged with 1/10 of the SA LD₅₀ (i.e., 280 mg/kg) daily for a month.
• Cell-culture concentrations: Cytotoxicity of shikimic acid was evaluated in HepG2 and Huh7 cells and 3T3-L1 cells after treatment with various concentrations: 0, 10, 20, 40, 80, and 160 µM.

Shikimic acid is commercially available as a purified powder and in star anise extracts. It is found in varying quantities as a naturally occurring constituent of Chinese star anise, sweetgum seed preparations, and pine needle teas or extracts used in folk traditions.

9. Pharmacokinetics

Pharmacokinetic analysis for shikimic acid demonstrated linear and dose-proportional behavior within the intravenous dose range of 4–16 mg/kg in mice. Shikimic acid was rapidly eliminated from plasma, with a short terminal half-life (T½) of 0.76–0.85 hours. Despite rapid absorption (T_max, 0.95–1.25 hours) following oral administration, a low bioavailability ranging from 11.09 to 20.44% was observed in mice. The pharmacokinetic properties and long-term safety profile of shikimic acid in humans remain inadequately characterized. The low oral bioavailability observed in mice raises important questions about whether systemically relevant concentrations can be achieved in humans following supplemental oral doses, which remain uninvestigated in formal human pharmacokinetic studies.

10. Safety Considerations

Acute and Subchronic Toxicity (Animal Data)

Acute toxicity testing in mice showed no mortality at oral doses of up to 10,000 mg/kg. In a 28-day subchronic oral toxicity study, mice fed diets containing high (50 g/kg), medium (16.67 g/kg), or low (5.56 g/kg) doses of shikimic acid exhibited no mortality. Hematological assessments revealed slight elevations in neutrophil counts, eosinophil counts, and hematocrit levels in the high-dose group compared to controls. Notably, a significant reduction in triglyceride levels was observed in the high-dose group, suggesting potential hypolipidemic effects.

SA is generally considered pharmacologically safe. Its pharmacological derivatives possess a wide range of bioactivities, combined with low toxicity.

Contamination Risk: Japanese Star Anise

A material safety concern relates to the risk of adulteration or confusion between Chinese star anise (Illicium verum), the commercially edible species, and Japanese star anise (Illicium anisatum). I. verum is sometimes contaminated with highly toxic Japanese star anise (I. anisatum L.) and poisonous star anise (I. lanceolatum A. C. Smith), which contain several neurotoxic sesquiterpenes. Japanese star anise is a highly toxic species and not meant for human consumption. Because shikimic acid supplements or star anise preparations derived from botanical sources may carry this contamination risk, sourcing and botanical authentication are important quality considerations.

Antiplatelet Interaction Potential

Shikimic acid has interesting biological properties, displaying activity as an anticoagulant and antithrombotic agent. Given the ex vivo evidence for antiplatelet effects targeting the P2Y1/P2Y12-ADP pathway, there is a theoretical potential for additive antiplatelet effects in individuals taking pharmaceutical antiplatelet or anticoagulant agents. This has not been studied in a clinical setting.

General Characterization of Evidence Gaps

The pharmacokinetic properties and long-term safety profile of shikimic acid in humans remain inadequately characterized. The wide range of bioactivities of shikimic acid and its derivatives indicate that a more detailed exploration of their potential for the prevention and treatment of certain diseases is warranted. As of the most recent literature reviewed, no published randomized controlled human trials have examined shikimic acid supplementation for any clinical endpoint. Evidence from in vitro and animal studies, while scientifically interesting, cannot be directly extrapolated to human supplementation contexts.

References

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• Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats — PubMed
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