cinamaldehído

Otros Nombres

(2E)-3-Phenyl-2-propenal(2E)-3-Phenylacrylaldehyde(2E)-3-Phenylprop-2-enal(E)-3-Phenyl-propenal(E)-3-Phenylprop-2-enal(E)-3-Phenylpropenal(E)-Cinnamaldehyde2-Propenal, 3-phenyl-2-Propenal, 3-phenyl-, (2E)-2-Propenal, 3-phenyl-, (E)-3-Phenyl-2-propen-1-al3-Phenyl-2-propenal3-Phenylacrolein3-Phenylacrylaldehyde3-Phenylprop-2-enal3-PhenylpropenalAldehyd cynamonowyAldehyd skoricovyAldéhyde cinnamiqueAldeide cinnamicaCassia aldehydeCinamaldehídoCinamaldehidoCinamaldeídoCinnamalCinnamaldehyde, (E)-Cinnamaldehyde, trans-Cinnamic aldehydecinnamic aldehyde, (E)-isomerCinnamyl aldehydeFahéjaldehidKaneelaldehüüdKaneelaldehydeKanelaldehydKanelialdehydiKorichny aldegidPhenylacroleinSinamaldehidatrans-3-Phenylacroleintrans-Cinnamaldehydetrans-Cinnamic aldehydetrans-CinnamylaldehydeZimtaldehydeβ-Phenylacrolein

Sinopsis

Cinnamaldehyde

1. Identity: Chemical and Botanical Profile

1.1 Names and Chemical Identity

Cinnamaldehyde is an organic compound with the formula C₉H₈O (also written C₆H₅CH=CHCHO). Occurring naturally as predominantly the trans (E) isomer, it gives cinnamon its flavor and odor. It is a phenylpropanoid that is naturally synthesized by the shikimate pathway.

Synonyms for cinnamaldehyde include 3-phenyl-2-propenal, cinnamic aldehyde, trans-cinnamaldehyde, cinnamal, cinnamyl aldehyde, cassia aldehyde, 3-phenylacrolein, and β-phenylacrolein. It is a yellowish oily liquid with a sweet taste and a cinnamish odor responsible for the characteristic taste and odor of cinnamon spice.

Structurally, cinnamaldehyde contains a substituted aldehyde group with an unsaturated carbon–carbon double bond, providing two electrophilic sites for reaction with receptors and enzymes. It has a molecular surface area of 194.04 Å³, a polar surface area of 17.07 Å², a log P of 1.98, and one hydrogen bond acceptor but no hydrogen bond donors — properties that satisfy Lipinski's rule of thumb for an orally active drug with improved pharmacokinetics.

1.2 Botanical Sources

This pale yellow, viscous liquid occurs in the bark of cinnamon trees and other species of the genus Cinnamomum. It is found in high concentrations in cinnamon essential oil. It occurs naturally in the bark of the cinnamon tree, Cinnamomum zeylanicum, which is native to Sri Lanka and India, and has been cultivated in other parts of the world, such as Brazil, Jamaica, and Mauritius. Cinnamaldehyde is also found in other members of the Cinnamomum species, including cassia and camphor.

Cinnamaldehyde constitutes about 90% of cinnamon bark essential oil. The essential oil from the bark of C. cassia and C. verum contains varying concentrations of trans-cinnamaldehyde, typically ranging between 1% and 12% in most samples. Cinnamaldehyde is also present in smaller amounts in the essential oils of hyacinth, myrrh, Bulgarian rose, and patchouli.

1.3 Isolation, Synthesis, and History of Discovery

Cinnamaldehyde was isolated from cinnamon essential oil in 1834 by Jean-Baptiste Dumas and Eugène-Melchior Péligot, and was synthesized in the laboratory by the Italian chemist Luigi Chiozza in 1854. The molecular formula for cinnamaldehyde was determined in 1834 by those French chemists, although its structural formula was deciphered only in 1866 by the German chemist Emil Erlenmeyer (1825–1909).

An early synthesis involved the aldol condensation of benzaldehyde and acetaldehyde. Today, cinnamaldehyde is extracted from Cinnamomum cassia and other species, providing diverse sources for varying chemical properties and therapeutic effects. Besides natural extraction, synthetic production and biotechnological methods like microbial fermentation offer scalable and sustainable alternatives.

1.4 Commercial Forms and Preparations

Cinnamaldehyde is prepared commercially by treating the bark of the Cinnamomum zeylanicum tree with steam. The aldehyde dissolves in the steam and can then be extracted as the steam cools and condenses to form cold water, in which the compound is much less soluble.

In commerce and research settings, cinnamaldehyde is encountered in several forms:

Cinnamon bark essential oil: Obtained by distilling the bark or leaves, it is highly concentrated in volatile compounds such as cinnamaldehyde, and widely used in aromatherapy, natural perfumery, and functional cosmetics.
Isolated trans-cinnamaldehyde: The natural product is trans-cinnamaldehyde, available as a highly purified liquid for research or flavoring use.
Cinnamon bark powder/extract capsules: In clinical studies, young Cinnamomum zeylanicum bark (Alba grade) from native Sri Lanka — in which trans-cinnamaldehyde was found to be a major chemical constituent (>60%) — has been used in randomized placebo-controlled trials, with participants receiving cinnamon capsules (1.5 g/day).
Encapsulated/nanoparticle formulations: Cinnamaldehyde has been loaded onto chitosan nanoparticles for anti-biofilm and delivery purposes, reflecting ongoing research into delivery technologies that address its chemical instability.
Food and flavoring applications: In addition to its uses as a herbal remedy, the primary use of cinnamaldehyde is as a food additive to enhance the flavor and/or odor of food products, most commonly in cake mixes, chewing gums, chocolate products, synthetic cinnamon oils, cola drinks, ice creams, soft drinks, and vermouth.

Cinnamaldehyde decomposes, in high humidity and high temperatures, to styrene, and, by reaction with oxygen as it ages, it darkens in colour and forms resinous compounds. This chemical instability is a significant consideration in formulation and storage.

2. Traditional and Historical Use

2.1 Ancient Chinese Medicine

Cinnamaldehyde was mentioned in Chinese medical texts as early as 2700 BCE, and was described in a famous Chinese medical text, the Tang Materia Medica, written in 659 CE. In traditional Chinese medicine (TCM), cinnamon bark (guì pí, Cinnamomum cassia) was used to warm the interior, dispel cold, relieve pain, and tonify yang energy. Cinnamon, a dried bark originating from the Cinnamomum genus, primarily originates from Guangxi, Guangdong, and Hainan provinces in China, and has been utilized for centuries as both an herbal remedy and a culinary spice.

2.2 Ayurvedic and Indian Traditions

Cinnamaldehyde has also been used for centuries in Ayurvedic medicine, the ancient healing art of India. A naturally occurring compound isolated from the bark of trees of the genus Cinnamomum, the extract and cinnamaldehyde have been used as a natural antidiabetic compound in India. Cinnamon was historically employed in Ayurveda for digestive complaints, respiratory ailments, and inflammatory conditions.

2.3 Ancient Egyptian Use

Cinnamon turns up in historical records as a gift to monarchs and an offering to the gods, and was used in Ancient Egypt as part of the mummification process. Ancient Egyptians used cinnamon in embalming and as a treatment for ailments, while traditional Chinese and Ayurvedic medicine recognized its warming properties, utilizing it to invigorate circulation, alleviate digestive discomfort, and fight infections.

2.4 Preservation and Culinary History

Before widespread refrigeration, antimicrobial spices were used to preserve and store perishable foods, including meat. The distinctive flavor and aroma of cinnamon are largely attributed to cinnamaldehyde, which has also been valued for its natural preservative qualities. Historically, cinnamon has played multiple roles in different cultures: as a spice, a natural preservative, ceremonial incense, and as an ingredient in herbal formulas.

2.5 Conditions Treated in Traditional Practice

Cinnamon has been used for many centuries to treat a wide variety of disorders, ranging from the common cold and the flu to diarrhea. Historically, cinnamon extracts have been prized in ancient civilizations such as Egypt, China, and India for their potential to support digestion, improve appetite, and address respiratory and inflammatory conditions.

Important note on evidence: Cinnamon has a long history of use in traditional medicine, including as a digestive aid; however, a survey was unable to find clear contemporary evidence of any significant medicinal or therapeutic effect. Traditional use accounts must be clearly distinguished from the experimental and clinical evidence reviewed below.

3. Phytochemistry: Key Constituents and the Position of Cinnamaldehyde

Cinnamon constituents include some 80 aromatic compounds, including eugenol, found in the oil from leaves or bark of cinnamon trees. Among these, cinnamaldehyde constitutes around 90% of the essential oil present in the bark. Other notable constituents identified by analytical methods include nonanal, acetic acid, α-copaene, benzaldehyde, ethyl cinnamate, trans-cinnamaldehyde, and coumarin.

The two commercially significant species differ in their chemical profiles: Cinnamon verum (originally from Ceylon/Sri Lanka) has a lighter, sweeter, more refined taste/flavour than Cinnamon cassia (originally from China), which has a stronger, harsher taste/flavour. Cassia bark also contains higher levels of coumarin, a hepatotoxic compound, than Ceylon cinnamon — a distinction with important safety implications not addressed by the cinnamaldehyde content alone.

4. Established Mechanisms of Action

4.1 TRPA1 Ion Channel Activation

Cinnamaldehyde is a bioactive electrophile that activates the transient receptor potential ankyrin 1 (TRPA1) ion channel, a chemosensory receptor expressed in sensory neurons and in the gastrointestinal tract. TRPA1 detects pungent or irritant compounds such as those found in cinnamon, mustard oil, and clove, producing the characteristic warming or burning sensation associated with these spices. In the gastrointestinal tract, TRPA1 activation by cinnamaldehyde influences the release of serotonin from enterochromaffin cells, linking chemical irritation with gut motility and sensory signaling.

The TRP channels family are cationic channels involved in various physiological processes including pain, inflammation, metabolism, swallowing function, gut motility, thermoregulation, and adipogenesis. In the oral cavity, TRP channels are involved in chemesthesis, the sensory chemical transduction of spicy ingredients. Among them, TRPA1 is activated by natural molecules producing pungent, tingling, or irritating sensations during their consumption.

4.2 Anti-inflammatory Pathways: NF-κB and Related Mediators

Cinnamaldehyde primarily operates by inhibiting the NF-κB pathway and modulating pro-inflammatory mediators. The 2′-hydroxycinnamaldehyde is known to inhibit the formation of nitric oxide by retarding the initiation of NF-κB, signifying the anti-inflammatory potential of this compound. Several bioactive components present in C. ramulus revealed potent anti-inflammatory characteristics due to inhibitory action on expression of nitric oxide, iNOS, and COX-2 production in the central nervous system.

4.3 Antidiabetic Mechanisms

Accumulating evidence supports the notion that cinnamaldehyde exhibits glucolipid-lowering effects in diabetic animals by increasing glucose uptake and improving insulin sensitivity in adipose and skeletal muscle tissues, improving glycogen synthesis in liver, restoring pancreatic islets dysfunction, slowing gastric emptying rates, and improving diabetic renal and brain disorders.

Cinnamaldehyde exerts these effects through its action on multiple signaling pathways, including PPARs, AMPK, PI3K/IRS-1, RBP4-GLUT4, ERK/JNK/p38MAPK, TRPA1-ghrelin, and Nrf2 pathways. In addition, cinnamaldehyde seems to regulate the activities of PTP1B and α-amylase.

Cinnamaldehyde lowers blood glucose levels in diabetic rats by enhancing glucose absorption, improving insulin sensitivity in adipose tissue, increasing glycogen synthesis in the liver, and exerting antioxidant properties. Nikzamir found that cinnamaldehyde down-regulates blood glucose by upregulating the expression of GLUT4 gene levels in mouse skeletal muscle. Saifudin reported that cinnamaldehyde inhibited protein tyrosine phosphatase-1B (PTP-1B), which helps prevent type 2 diabetes and obesity.

4.4 Antimicrobial Mechanisms

Trans-cinnamaldehyde has broad-spectrum antimicrobial activity, targeting both Gram-positive and Gram-negative bacteria as well as various fungi, positioning it as a potent natural antimicrobial agent. Trans-cinnamaldehyde changes the cell membrane's permeability and attacks the mitochondria, leading to the production of reactive oxygen species (ROS) and leakage of intracellular substances such as Na⁺, K⁺, and proteins.

Cinnamaldehyde's antimicrobial activity has been linked to a variety of mechanisms, some of which overlap. The mechanism of cinnamaldehyde's bactericidal action against L. monocytogenes and E. coli has been studied, and it appears that interaction with the cell membrane causes a rapid inhibition of energy metabolism.

With respect to antifungal mechanisms: The molecular mechanisms through which cinnamaldehyde inhibits the growth of fungi are highly intricate, principally encompassing the inhibition of ATPase activity, the suppression of cell wall or biofilm formation, as well as the alteration of the structure and integrity of the cell membrane.

4.5 Anti-biofilm and Quorum-Sensing Inhibition

Recent studies have highlighted cinnamaldehyde's role in disrupting microbial membranes, inhibiting biofilm formation, and modulating key metabolic pathways in pathogens. Low concentrations of cinnamaldehyde negatively affect two types of quorum sensing (QS) related to acyl homoserine lactone (AHL) and autoinducer-2. Combining cinnamaldehyde with colistin produces synergistic activity in the inhibition and dispersion of preformed P. aeruginosa biofilm.

4.6 Anticancer Mechanisms (Preclinical)

Extensive research has demonstrated that cinnamaldehyde exhibits promising anticancer properties by modulating various cellular processes involved in tumor growth and progression. However, challenges and unanswered questions remain regarding the precise mechanisms for its effective use as an anticancer agent.

Cinnamaldehyde has diverse anti-cancer mechanisms, including inducing apoptosis by activating caspases and damaging mitochondrial function, inhibiting tumor angiogenesis, and exerting anti-proliferative and anti-inflammatory effects. It demonstrates how cinnamaldehyde hinders the formation of new blood vessels by suppressing vascular endothelial growth factor and inhibiting the proliferation of endothelial cells. This antiangiogenic effect is instrumental in reducing the nutrient supply to tumors, thereby impeding their growth and metastasis.

4.7 Thermogenesis and Adipogenesis

Cinnamaldehyde has been proposed to exert its anti-obesity effect via (i) inhibiting the differentiation of pre-adipocytes to mature adipocytes, (ii) modulating lipolysis and lipid biosynthesis of adipocytes, as well as (iii) activating thermogenesis and metabolic reprogramming. Chronic ingestion of cinnamaldehyde reduces visceral adipose tissue in rodents and increases UCP1 expression in brown adipose tissue (BAT). It has been proposed that TRPA1 could increase metabolism through cold sensing and thermogenesis stimulation in BAT.

5. Scientific Evidence by Area of Use

5.1 Glycemic Control and Diabetes

Preclinical evidence: In a study using streptozotocin-induced male diabetic Wistar rats, cinnamaldehyde administered at different doses (5, 10, and 20 mg/kg body weight) for 45 days produced a significant, dose-dependent decrease in plasma glucose concentration (63.29% compared to controls). The LD₅₀ value of cinnamaldehyde in this model was determined as 1850 ± 37 mg/kg body weight.

Results in diabetic rats indicated that cinnamaldehyde normalized fasting blood glucose and decreased HOMA-IR (a measure of insulin resistance). A proposed mechanism of fasting blood glucose lowering by cinnamaldehyde involves its ability to activate phosphoenol pyruvate carboxykinase (PEPCK) and pyruvate kinase (PK), which promote the synthesis of glycogen and the inhibition of gluconeogenesis.

Clinical evidence: A randomized, double-blinded, placebo-controlled trial was carried out from January 2020 to March 2022 at the Diabetic Clinic at AIIMS Rishikesh, India. A total of 154 diabetic patients were enrolled and took either cinnamon or placebo capsules (1.5 g/day) for 120 days on an empty stomach with warm water, along with their conventional treatment. Reduction in fasting blood glucose levels in the cinnamon group was –35.50% (95% CI, –173 to 58.4), whereas in the placebo group the change was +5.00% (95% CI, –165 to 224).

A 2023 meta-analysis of six meta-analyses found that cinnamon supplementation can lead to modest but significant decreases in fasting plasma glucose and haemoglobin A1c (HbA1c).

Evidence characterization: Preclinical (animal) evidence is substantial and mechanistically detailed. Human clinical evidence — specifically for isolated cinnamaldehyde — remains limited; most clinical trials have used whole cinnamon bark preparations rather than purified cinnamaldehyde. The meta-analytic signal for cinnamon on fasting glucose and HbA1c is modest, and the translation of animal-derived cinnamaldehyde data to humans requires further investigation.

5.2 Anti-inflammatory Effects

Multiple reviews drawing on PubMed, Web of Science, and ScienceDirect outline cinnamaldehyde's efficacy in treating inflammatory conditions, among other diseases. It primarily operates by inhibiting the NF-κB pathway and modulating pro-inflammatory mediators.

A water extract of cinnamon was reported to have anti-allergic, anti-inflammatory, antipyretic, analgesic, and antithrombotic effects in experimental settings. However, the majority of anti-inflammatory evidence derives from in vitro and animal studies. Direct human clinical evidence for cinnamaldehyde as an isolated anti-inflammatory agent is not currently established in registered randomized controlled trials.

5.3 Antimicrobial Activity

The essential oil from Cinnamomum tree bark is rich in trans-cinnamaldehyde, which has antimicrobial effects against animal and plant pathogens, food poisoning, and spoilage bacteria and fungi. Numerous studies have shown that cinnamaldehyde possesses extensive antibacterial, yeast, and filamentous mold activities.

Being structurally similar to the AHL molecules 3-oxo-C12-HSL and C4-HSL, cinnamaldehyde can strongly interact with quorum-sensing receptors, attenuating the QS circuits, inhibiting biofilm formation, and lowering bacterial virulence and motility.

Antifungal evidence: In a pharmaceutical orabase antifungal susceptibility test, cinnamaldehyde exhibited antifungal activity at concentrations greater than 200 μg/mL. The orabase ointment formulation proved to be safe for use on keratinized mucosa up to the maximum concentration tested (700 μg/mL).

Evidence characterization: Antimicrobial evidence for cinnamaldehyde is predominantly in vitro. While these findings are consistent across many studies and bacterial/fungal species, clinical trials demonstrating efficacy in treating human infections with cinnamaldehyde are lacking. In vitro minimum inhibitory concentrations (MICs) do not necessarily translate to safe and achievable in vivo concentrations.

5.4 Anticancer Activity

Cinnamaldehyde has garnered attention in pharmacological research due to its diverse therapeutic applications. It has potential in treating a wide array of conditions including cardiovascular diseases, diabetes, inflammatory disorders, and various forms of cancer.

Cinnamaldehyde, an active compound derived from the natural plant cinnamon, has attracted attention in pharmacological research due to its diverse therapeutic applications. It has potential in treating conditions including cardiovascular diseases, diabetes, inflammatory disorders, and various forms of cancer. Reviews comprehensively summarize the physicochemical and pharmacokinetic profiles of cinnamaldehyde, and delve into the latest advancements in elucidating its potential mechanisms and targets across various cancer types.

Evidence characterization: All existing anticancer evidence for cinnamaldehyde is preclinical — derived from cell lines and animal models. Extensive research has demonstrated that cinnamaldehyde exhibits promising anticancer properties by modulating various cellular processes involved in tumor growth and progression. However, challenges and unanswered questions remain regarding the precise mechanisms for its effective use as an anticancer agent. No completed human clinical trials evaluating cinnamaldehyde as a cancer treatment have been identified in the peer-reviewed literature at this time.

5.5 Cardiovascular and Metabolic Effects

Cinnamaldehyde enhances metabolic health by improving glucose uptake and insulin sensitivity and offers cardiovascular protection through its anti-inflammatory and lipid-lowering effects. Experiments showed that cinnamaldehyde could effectively improve vascular endothelium-dependent diastolic function with an antihypertensive trend, providing experimental evidence for further cinnamaldehyde clinical use.

Cinnamaldehyde decreases blood glucose levels in a dose-dependent manner and has also been shown to reduce triglycerides and cholesterol.

Evidence characterization: Cardiovascular evidence is predominantly from animal studies. The vascular effects (endothelium-dependent relaxation, lipid lowering) are promising at the preclinical level, but human cardiovascular trial data for isolated cinnamaldehyde are currently absent.

5.6 Obesity and Thermogenesis

Cinnamaldehyde, a well-known potent TRPA1 agonist from cinnamon, is reported to impact metabolism and exert anti-obesity and anti-hyperglycemic effects. In humans, after a single dose of cinnamaldehyde ingestion, post-prandial energy expenditure and fat oxidation were maintained higher than in placebo conditions. It might be speculated that long-term antidiabetic effects of TRPA1 agonists such as cinnamaldehyde and cuminaldehyde are due to increased energy expenditure and fat oxidation.

Evidence characterization: A single human study demonstrated an acute thermogenic effect, but evidence for sustained, clinically meaningful anti-obesity effects in humans is not yet established. Animal data (visceral fat reduction, increased UCP1 in BAT) is intriguing but not directly translatable.

5.7 Kidney Disease

Cinnamaldehyde additionally promotes autophagy in kidney disease management. Chronic cinnamaldehyde post-treatment in a diabetic nephropathy rat model significantly improved fasting blood glucose (from 20.2 ± 1.2 to 10.0 ± 0.7 mmol/L, P < 0.01) and serum insulin levels.

Evidence characterization: Renal evidence is exclusively preclinical (rodent diabetic nephropathy models). No human kidney disease trials have been conducted.

5.8 Neuroprotection

Cinnamaldehyde has a broad range of pharmacological effects, including neuroprotective effects, which largely contribute to the prevention and treatment of various diseases such as neurodegenerative diseases. Cinnamaldehyde also has multiple pharmacological activities such as neuroprotective and cardioprotective effects.

Evidence characterization: Neuroprotective effects are documented in cellular and animal models. No clinical trials in human neurodegenerative conditions have been identified.

6. Pharmacokinetics

Cinnamaldehyde satisfies Lipinski's rule of thumb for orally active drugs, with a log P of 1.98, one hydrogen bond acceptor, and no hydrogen bond donors, suggesting favorable pharmacokinetics for oral delivery.

Cinnamaldehyde has the potential of metabolizing into cinnamyl alcohol, methyl cinnamate, and cinnamic acid in the body. These metabolites may themselves contribute to biological activity.

Cinnamaldehyde is a yellow oily liquid with low solubility in water, and is soluble in ethanol and chloroform. Its poor aqueous solubility and chemical reactivity (the α,β-unsaturated aldehyde group is prone to nucleophilic addition) present formulation challenges that have driven interest in encapsulated delivery systems.

7. Dosage Forms and Reported Dosages

No universally established therapeutic dose for cinnamaldehyde as a standalone supplement exists. The following represent dosages reported in specific studies:

Animal studies (oral, antidiabetic): Cinnamaldehyde was administered at different doses (5, 10, and 20 mg/kg body weight) for 45 days to streptozotocin-induced male diabetic Wistar rats.
Animal studies (antidiabetic, STZ model): Cinnamaldehyde was given to rats orally by gastric tube at a dose of 40 mg/kg/day for one month.
Animal studies (general therapeutic range): Many researchers have used cinnamaldehyde at a dose range of 5–80 mg/kg for different periods and have suggested beneficial effects in improving pathological conditions such as diabetes, memory impairment, and organ injury.
Human clinical trial (cinnamon bark capsules): A total of 154 diabetic patients received either cinnamon or placebo capsules at 1.5 g/day for 120 days. The trans-cinnamaldehyde content of these capsules was confirmed to be greater than 60% of the bark preparation.
Food-grade exposures: Food-grade cinnamaldehyde is used in non-alcoholic beverages, ice cream, candy, baked goods, chewing gum, condiments, and meats at levels ranging from 9 ppm to 4,900 ppm.

8. Safety Considerations

8.1 Regulatory Status

Cinnamaldehyde is generally regarded as safe (GRAS) by the United States Food and Drug Administration (USFDA) and the Flavor/Extract Manufacturers' Association (FEMA) as a flavor ingredient, while the Council of Europe has grouped cinnamaldehyde into the list of substances with 'A' status, meaning 'may be used in foodstuffs.'

The FDA, under section number 121.101, classifies cinnamaldehyde as GRAS (generally recognized as safe), limited to use as a synthetic flavor/adjuvant. Under 21 CFR 182.60, it is listed as a Synthetic Flavoring Substance and Adjuvant, GRAS for its intended use when used in accordance with good manufacturing or feeding practice.

The Joint FAO/WHO Expert Committee on Food Additives (JECFA) established a temporary acceptable daily intake (ADI) of up to 700 μg per kg body weight.

8.2 Acute Toxicity

Cinnamaldehyde produced nearly 100% mortality in rats when used at a dose of 940 mg/kg/day for 2 weeks. In addition, oral administration of cinnamaldehyde at a dose of 500 mg/kg for 14 days induced genetic alterations at the chromosomal level in the liver of rats. These findings indicate that doses above 500 mg/kg of cinnamaldehyde may be lethal and toxic.

The LD₅₀ value of cinnamaldehyde in rats was determined as 1,850 ± 37 mg/kg body weight.

In non-mammalian toxicity models: In Galleria mellonella larvae, cinnamaldehyde was not toxic up to the highest dose tested (20 mg/kg) and presented no genotoxicity up to the dose of 4 mg/kg in a mouse model. However, it was found to be toxic in zebrafish embryos up to a concentration of 0.035 μg/mL.

8.3 Skin and Mucosal Sensitization (Contact Dermatitis)

This is the most clinically important and well-documented safety concern for cinnamaldehyde. A toxicologic and dermatologic review of cinnamaldehyde when used as a fragrance ingredient documents that trans-cinnamaldehyde and trans-cinnamic alcohol cause allergic contact dermatitis (ACD) in humans, and cinnamaldehyde is a more potent sensitizer than cinnamic alcohol.

These two chemicals are principal constituents of the European Standard 'Fragrance Mix,' used in patch-testing diagnostics of sensitization to fragrances by clinical dermatologists. For several decades, Fragrance Mix I — a mixture of seven synthetic substances including cinnamal (cinnamaldehyde) at 1% each — has been used in patch test standard series for clinical diagnosis of fragrance sensitization.

The European Parliament and the Council of the European Union have placed cinnamaldehyde on the list of fragrance materials that must be labeled on consumer products (7th Amendment to Council Directive 76/768/EEC) because of their potential for allergenicity.

Cinnamaldehyde can induce intraoral allergic contact dermatitis; it is widely used as a flavoring agent in foods and dentifrices and this represents an important exposure route.

Contact allergy to fragrance ingredients occurs when an individual has been exposed, on the skin, to a sufficient degree of fragrance contact allergens. Contact allergy is a life-long, specifically altered reactivity in the immune system — meaning that once contact allergy is developed, cells in the immune system will be present which can recognize and react toward the allergen. As a consequence, allergic contact dermatitis may occur upon re-exposure. Allergic contact dermatitis is an inflammatory skin disease characterized by erythema, swelling, and vesicles in the acute phase. If exposure continues, it may develop into a chronic condition with scaling and painful fissures of the skin.

8.4 Primary Skin and Eye Irritation

Cinnamaldehyde is a primary eye irritant as determined by exposure of human subjects to solutions of 8% active ingredient. It is also a moderate skin irritant.

8.5 Dual-Character: Pro- vs. Anti-inflammatory

It has been shown that low concentrations (up to 1 μg/mL) of cinnamaldehyde induce a slight increase in nuclear factor-κB (NF-κB) activation, suggesting a degree of intrinsic pro-inflammatory activity at low concentrations — a finding that adds nuance to the predominantly anti-inflammatory profile reported at higher studied concentrations. This bidirectional pharmacology at different concentrations warrants attention in dosing research.

8.6 Genotoxicity Concerns at High Doses

Oral administration of cinnamaldehyde at a dose of 500 mg/kg for 14 days induced genetic alterations at the chromosomal level in the liver of rats, indicating that doses above 500 mg/kg may be lethal and toxic. These toxicological thresholds are orders of magnitude above the food-flavoring exposures typical for humans but are pertinent for high-dose supplementation contexts.

8.7 Biofilm Interactions and Drug Synergy

Combining cinnamaldehyde with colistin produces synergistic activity in the inhibition and dispersion of preformed P. aeruginosa biofilm. Such synergistic interactions with antibiotics are an emerging area of research; however, potential interactions with co-administered pharmaceutical agents in humans have not been systematically evaluated in clinical trials.

9. Body Systems and Health Domains

Cinnamaldehyde's range of documented pharmacological effects includes anti-inflammatory, antioxidant, antiviral, antibacterial, antithrombic, hypoglycemic, hepatoprotective, antidiabetic, neuroprotective, and anticancer effects, which largely contribute to research into the prevention and treatment of various diseases including inflammatory diseases, neurodegenerative diseases, cardiovascular disease, diabetes mellitus, and cancer.

In summary, the body systems in which cinnamaldehyde has been studied include:

Endocrine/metabolic: Glycemic regulation, insulin sensitivity, lipid metabolism, obesity (TRPA1-mediated thermogenesis)
Cardiovascular: Vascular endothelial function, blood pressure (antihypertensive trend), atherosclerosis (lipid modulation)
Immune/inflammatory: NF-κB inhibition, cytokine modulation, anti-allergic potential
Gastrointestinal: Gut motility (via TRPA1/serotonin), antimicrobial against food-borne pathogens
Renal: Diabetic nephropathy models, autophagy promotion
Neurological: Neuroprotection in preclinical models
Oncology: Apoptosis induction, anti-angiogenesis, anti-proliferation in cancer cell lines and animal models
Dermatological: Allergen/sensitizer at topical exposures; antimicrobial in wound/mucosal contexts

Preclinical and clinical research supports cinnamaldehyde's therapeutic potential, underscoring the need for further investigation into its mechanisms and safety to develop new drugs based on cinnamaldehyde.

10. Overall Evidence Assessment

Cinnamaldehyde sits at an advanced preclinical stage across most investigated health applications. Mechanistic work — particularly regarding NF-κB, TRPA1, AMPK, GLUT4, and apoptotic pathways — is detailed and growing. In vitro antimicrobial, antifungal, and anti-biofilm evidence is extensive. Animal model data for antidiabetic, anti-inflammatory, and anti-obesity effects is robust but carries the inherent limitations of inter-species translation. Human clinical evidence remains sparse and primarily derived from whole-cinnamon preparations rather than purified cinnamaldehyde, making it difficult to attribute clinical outcomes specifically to this compound. The allergenic and irritant potential is the best-characterized safety concern and is backed by decades of patch-test data and formal regulatory action in the EU. Large, well-controlled human trials using standardized cinnamaldehyde preparations are needed before firm clinical recommendations can be made in any therapeutic area.

References

Condiciones de Salud

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Energía (falta de)Científico
Cinnamaldehyde, the principal bioactive compound (approximately 90%) of cinnamon essential oil, has documented antifungal activity against Candida albicans in vitro by disrupting biofilm formation and inhibiting the yeast-to-hyphal transition. Combined with eugenol it shows synergistic anti-Candida activity in PMC-published research. It is the pharmacologically active basis for cinnamon's anti-Candida use.
SorderaTradicional
Cinnamaldehyde is the primary bioactive of cinnamon bark oil, with antimicrobial activity against oral pathogens including Streptococcus mutans and Candida albicans. It contributes to cinnamon's traditional use as a dental analgesic and antibacterial. Multiple in vitro studies confirm its action against cariogenic bacteria, and it is referenced in dental literature as an active component of cinnamon's oral health benefits.

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