IngredientsNeral is a naturally occurring acyclic monoterpene aldehyde and the Z-geometric isomer of the well-known compound citral. Citral consists of two geometrical isomers — geranial (citral A, the E-isomer) and neral (citral B, the Z-isomer) — in approximately a 3:2 ratio in natural plant sources. Neral is formally named cis-3,7-dimethyl-2,6-octadien-1-al, while its counterpart geranial is trans-3,7-dimethyl-2,6-octadien-1-al.
The molecular formula shared by both isomers is C10H16O; citral as a mixture is also referred to by the systematic IUPAC name 3,7-dimethylocta-2,6-dienal. Being a monoterpene, citral is built from two isoprene units. The E-isomer is named geranial (or α-citral), and the Z-isomer is named neral.
Neral (as part of the citral mixture) appears as a pale yellow, oily liquid at room temperature with a strong lemon aroma and a boiling point of 226–228°C. It is insoluble in water but readily soluble in organic solvents. Both isomers are insoluble in water and have a density equal to 0.891–0.897 at 15°C.
Geranial, the trans-isomer, is the more potent of the two with a strong, sharp lemon odor, while neral is softer and slightly sweeter. Due to their geometric differences, neral and geranial present different LogP values among several physicochemical characteristics.
Citral — and by extension neral — is an α,β-unsaturated aldehyde with highly reactive chemical properties. Neral and geranial both carry an aldehyde functional group, which is an electrophilic moiety capable of reacting with amino residues of proteins, making this functional group one that is ordinarily avoided in drug development due to potential for undesirable effects and toxicity.
Neral occurs naturally as a major volatile constituent in a wide range of aromatic plant species. This monoterpene is found in different plants, citrus fruits, herbs, and grasses; it is one of the most prevalent components of essential oils of Cymbopogon species, mainly East Indian (C. flexuosus) and West Indian species (C. citratus), commonly known as lemongrass, with a citral content of 70–85%.
Citral (and hence neral) is also present in other plant oils, including Lindera citriodora, Calypranthes parriculata, petitgrain, Aloysia citrodora, lemon ironbark, lemon balm, lime, lemon, orange, and lemon tea-tree; it can further be found in a wide diversity of plant leaves and fruits, including limes, oranges, lemons, tomatoes, myrtle trees, and African basil.
The essential oil of Backhousia citriodora, commonly known as lemon myrtle oil, is another particularly rich source; GC-MS analysis of this oil identified 21 compounds representing 98.50% of the total oil content, with the citral isomers geranial (52.13%) and neral (37.65%) as the main constituents.
The primary host plant, Cymbopogon citratus, is a native herb from southern India and Sri Lanka, but nowadays grows spontaneously all over the world, especially in other tropical, subtropical, and savannah regions. Steam distillation of lemongrass oil from India and Sri Lanka yields high concentrations of citral. Litsea cubeba from China is another major commercial source. Lemon myrtle plantations in Australia also yield citral-rich oils, and citral is also manufactured synthetically on a large scale from petrochemical feedstocks including isobutylene and formaldehyde.
For specific applications in the field of aroma or synthesis chemistry, it may be desirable to use the two double-bond isomers (neral and geranial) in pure or enriched form; however, these compounds differ only by the configuration of the ethylenic double bond conjugated to the aldehyde group and can be interconverted readily by thermal isomerization.
Citral (neral + geranial) is considered an important raw material in the fragrance, pharmaceutical, food, and cosmetic industries. It is generally obtained from lemongrass (Cymbopogon flexuosus) by fractional distillation, adduct formation, or chromatography columns. It can also be used as a starting material for the synthesis at industrial scale of various commercially important compounds, including menthol, ionones, and vitamin A.
Citral is used industrially for the synthesis of vitamin A and β-ionones and other specialty chemicals. Typically, commercial compositions between neral and geranial are complementary, with each isomer ranging from 48 to 52% of commercial citral mixtures.
Neral does not have a historical record as an isolated compound — its history is embedded in the ethnopharmacological and culinary traditions of the citral-rich plants from which it derives, most notably lemongrass and lemon balm.
Lemongrass (Cymbopogon citratus) has a long history of use dating back thousands of years in traditional medicine, culinary practices, and cultural rituals across Asia, Africa, and South America. Originating in tropical and subtropical regions, particularly India, Sri Lanka, and Southeast Asia, lemongrass has been cultivated and valued for its aromatic, medicinal, and culinary properties for centuries. In ancient India and China, lemongrass was widely used in Ayurvedic and traditional Chinese medicine to treat digestive issues, fever, infections, and inflammation.
Lemongrass has a long history of use as a seasoning in food and medicine in China and elsewhere; it is frequently used in flavored food because of its distinctive scent, and in Southeast Asian countries and China, many foods are often seasoned with lemongrass, including soups, berries, chicken, and pork dishes.
In Ayurveda, India's traditional treatment system, lemongrass essential oil treats hypertension, fever, stomach disease, and inflammation related to rheumatism, colds, and flu. In traditional medicine of India, the leaves of the plant are used as stimulant, sudorific, antiperiodic, and anticatarrhal agents, while the essential oil is used as a carminative, depressant, analgesic, antipyretic, antibacterial, and antifungal agent.
The plant is sometimes prepared from fresh herbs in the form of infusions and decoctions; the dried leaves are given mostly in the form of tea in most continents for a broad range of indications. In the continents of Asia, South America, and Africa, the leaves have traditionally been utilized as tea or decoction; these leaves contain essential bioactive compounds that determine the plant's various ethno-medicinal properties.
In different cultures, lemongrass is referred to by various names: Tanglad in the Philippines, Sereh in Indonesia and Malaysia, Takrai in Thailand, and Xiāng máo in China.
Traditional uses of citral-rich plants in ethnopharmacology, particularly in Asia, Africa, and South America, have long underpinned their application in managing symptoms of inflammation.
Based on the literature reviewed, citral is the active natural agent in Cymbopogon citratus accountable for most of its pharmacological activities. The plant is sometimes prepared from fresh herbs in the form of infusions and decoctions, and the dried leaves are given mostly in the form of tea in most continents for a broad range of indications.
While neral is itself the active constituent under discussion, it is important to understand its chemical context. To date, 158 compounds have been reported in Cymbopogon citratus, including terpenoids, flavonoids, and phenolic acids. Among these, the citral fraction — composed of neral and geranial — is responsible for the characteristic lemon odor and is the principal bioactive contributor. Lemongrass oil contains 65–85% citral in addition to myrcene, citronellal, citronellol, linalool, and geraniol.
In Lippia alba plants, the major component is citral (a mixture of neral and geranial) ranging from 70.6% to 79.0%, while oxygenated monoterpenes found include linalool (1.7–2.2%), nerol (0.5–2.5%), geraniol (0.8–2.0%), and geranyl acetate (0.8–1.4%).
Citral and its isomers, including neral, are susceptible to oxidation and deterioration due to their conjugated double bonds and aldehyde groups. Currently, mainstream solutions to improve stability include acetalization and microencapsulation.
Citral (and its isomers neral and geranial) has been shown to modulate key inflammatory pathways, including the inhibition of COX-2 and NF-κB, reduction of pro-inflammatory cytokines, and activation of peroxisome proliferator-activated receptors (PPARs). These molecular actions support the ability to alleviate inflammation in various systems, including respiratory, gastrointestinal, neuroinflammatory, and orofacial conditions.
The anti-inflammatory mechanism of citral is attributed to the inhibition of NF-κB signaling. Citral activates peroxisome proliferator-activated receptor PPAR-γ and inhibits IκB phosphorylation, which independently blocks NF-κB activity with the consequent inhibition of gene expression of the inflammatory mediator.
Research investigating the anti-inflammatory activity of neral and geranial specifically has concluded that neral, in addition to having anti-inflammatory activity, is responsible for the antioxidant activity of the citral compound, while geranial is identified as the more potent molecule against fungi.
The lipophilic nature of citral enables it to permeabilize the cell membrane, disrupt cell integrity, cause the leakage of cellular components, and ultimately lead to cell death.
The transcriptomic profile has revealed that citral provokes cell integrity disturbance, specifically by disrupting fungal spores and inhibiting the biosynthesis of ergosterol, a major structural constituent of fungal cell membranes. Research has confirmed that citral can exert its antifungal effect through inhibition of ergosterol biosynthesis.
In studies on Penicillium digitatum, 41 over-expressed and 84 repressed proteins were identified after 1.0 μL/mL of citral exposure for 30 minutes using the iTRAQ technique. The proteins were closely related to oxidative phosphorylation, the TCA cycle, and RNA transport; the mitochondrial complexes I, II, III, IV, and V involved in oxidative phosphorylation were drastically affected.
Investigations have demonstrated that citral exhibits several biological activities, including antibacterial, antifungal, antibiofilm, antiparasitic, antiproliferative, anti-inflammatory, and antioxidant properties, based on both in vitro and in vivo assays. The antibacterial effect of citral is similarly attributed primarily to disruption of the bacterial cell membrane, altering its permeability and causing leakage of intracellular contents.
Studies show that citral effectively inhibits the proliferation of cancer cells in in vitro models. This effect has been associated with the capacity of this bioactive compound to induce apoptosis and cause cell cycle arrest via induction of reactive oxygen species (ROS) production and modification of related pathways.
The possibility of covalent bond formation generating an imine group (Schiff base) with many enzymes on the path to the target can explain why encapsulated citral shows a greater antiproliferative action than free citral.
The protective effects of citral include the ability to act as a direct antioxidant agent by scavenging reactive oxygen species (ROS); indirect antioxidant effects (induction of enzymatic and non-enzymatic cellular antioxidants — GSH and SOD) and inducing phase II detoxifying enzymes may also be involved.
Citral (3,7-dimethyl-2,6-octadienal), a major active compound in Litsea cubeba, a traditional Chinese herbal medicine, can inhibit oxidant activity, macrophage, and NF-κB activation.
Citral has exhibited a broad spectrum of biological activities, and has been described as an effective antimicrobial agent against different Gram-positive and Gram-negative bacteria, fungi, and parasites of clinical relevance.
Citral, extracted from Pectis plants, is a monoterpene naturally composed of geometric isomers neral (cis-citral) and geranial (trans-citral). It has promising antifungal activities and ergosterol biosynthesis inhibition effects against several pathogenic fungi. However, at the time of relevant publications, no study had specifically focused on neral and geranial individually against T. rubrum, which hindered clinical application of citral; one study aimed to compare antifungal activities of neral and geranial specifically and to elucidate their ergosterol biosynthesis inhibition mechanism against T. rubrum.
In an in vitro study of citral against Candida albicans, the MIC and MFC of citral were 64 μg/mL and 256 μg/mL respectively. Involvement with the cell wall and ergosterol binding were excluded as possible mechanisms. In the morphological interference assay, the compound inhibited pseudohyphae and chlamydoconidia formation. At both the MIC and MFC, only 4 hours of exposure were required to effectively kill 99.9% of the inoculum.
In a study of fluconazole-resistant Candida tropicalis, the MIC90 and MFC90 of citral were 512 and 1024 μg/mL respectively. The MIC did not increase when sorbitol or ergosterol was added to the medium, suggesting that citral does not act on the cell wall or by membrane ergosterol binding. However, citral inhibited ergosterol biosynthesis, and the citral–fluconazole combination showed synergistic effects for the ATCC strain.
Several citral antifungal mechanisms have been reported across studies, including cell wall damage, mitochondrial membrane potential disruption, and membrane damage.
Evidence characterization: Antifungal evidence for neral/citral is predominantly in vitro (cell-based and microbiological). No controlled clinical trials (human subjects) on neral as a standalone antifungal therapeutic have been published in the reviewed literature. Evidence is preliminary to moderate (preclinical).
In one study, the anti-inflammatory activity of citral was evaluated in male mice infected with S. aureus. Results indicated that citral inhibited the expression of NO synthase and some features of acute inflammation, such as monocyte numbers and the gene transcription of the pro-inflammatory cytokine TNF-α.
The anti-inflammatory activity of citral in RAW 264.7 cells (mouse macrophages) in the presence and absence of lipopolysaccharide (LPS) was evaluated in a separate study. Citral inhibited nitric oxide (NO) production by 84% and 99% at the lowest (5 μg/mL) and highest tested concentrations (20 μg/mL), respectively.
Melissa officinalis is a rich source of the monoterpene aldehydes linked to geraniol and nerol (specifically geranial and neral), and these compounds have demonstrated anti-inflammatory activity in research settings.
Evidence characterization: Anti-inflammatory evidence for neral/citral is predominantly derived from in vitro cell culture and animal (rodent) models. There is a limited body of human/clinical evidence. Most studies investigate citral as a mixture rather than isolated neral specifically. Evidence strength is preliminary to moderate (preclinical).
In one study examining volatilized citral isomers against breast cancer cells, the IC50 was reported as 1.67 μL/mL for geranial and 1.31 μL/mL for neral. Volatilized citral alone showed strong antiproliferation and infiltration-inhibiting effects. The transpiration components of lemongrass, lemon myrtle, litsea, and melissa are thought to inhibit breast cancer cell proliferation due to their high levels of citral.
Studies show that citral effectively inhibits the proliferation of cancer cells in in vitro models, and this effect has been associated with the capacity of citral to induce apoptosis and cause cell cycle arrest via induction of ROS production.
Evidence characterization: Anticancer evidence is exclusively in vitro (cell line based), with some animal model data. There are no human clinical trials on neral as an anticancer agent. This area is considered early-stage and experimental.
The monoterpene aldehydes geranial and neral, isolated from ethyl acetate extracts of Doronicum kotschyi and D. subcapitatum, were reported to have trypanocidal activity against epimastigotes of T. cruzi, with a minimum lethal concentration (MLC) of 3.1 μM.
The presence of geranial and neral, as a mixture (citral), is reported to be responsible for activity of the essential oil of Nepeta cataria against T. cruzi.
Evidence characterization: Antiparasitic evidence is in vitro and early-stage. No human clinical data exist for neral in this context.
Research on the anti-inflammatory activity of isolated neral and geranial concluded that neral — in addition to having anti-inflammatory activity — is specifically responsible for the antioxidant activity of the citral compound. This finding distinguishes neral from its geranial isomer, suggesting a potentially distinct role in radical scavenging activity.
Evidence characterization: Antioxidant evidence is in vitro and in vivo (animal). No isolated human clinical trials on neral as an antioxidant supplement have been identified in the reviewed literature.
Citral (3,7-dimethyl-2,6-octadienal), a major active compound in Litsea cubeba, can inhibit oxidant activity, macrophage, and NF-κB activation. In one study, researchers used a mouse model of focal segmental glomerulosclerosis (FSGS) featuring glomerular epithelial hyperplasia lesions (EPHLs), peri-glomerular inflammation, and progressive glomerular hyalinosis/sclerosis, to examine citral's renoprotective potential.
Evidence characterization: This is an animal model study; there are no confirmed human clinical data for neral/citral in kidney disease management.
The biofilm inhibitory concentration value for citral was determined to be 64 μg/mL in one study. As an antifungal agent, citral targets the cell membrane, in contrast to thymol, which targets the cell wall.
Evidence characterization: Antibiofilm evidence is in vitro only. This area remains at the preclinical stage.
Citral, including its isomers, is cited in the pharmaceutical literature for several activities relevant to the nervous system, including anxiolytic, analgesic, and antiepileptic properties. Citral exhibits calming and anxiolytic properties and has been shown to modulate neurogenic, respiratory, gastrointestinal, and orofacial inflammation, as well as play a role in autoimmune disease management.
Evidence characterization: Neurological effects attributed to neral/citral are largely based on preclinical (animal and in vitro) data. Human clinical evidence for anxiolytic or analgesic activity of isolated neral is not established in the reviewed literature.
Neral is not clinically standardized as a standalone dietary supplement. It is encountered in:
The following dosages have been reported in specific studies, applied to citral as a mixture of neral and geranial:
No standardized human clinical dosing protocols for isolated neral as a dietary supplement have been identified in the reviewed literature.
Citral (the neral/geranial mixture) is present in different plant sources and is recognized as safe (GRAS) by the Food and Drug Administration (FDA). This designation applies to its use as a citrus base flavoring in food products at levels consistent with food use.
Data from formal toxicological assessments show that citral is not genotoxic. Available data provide a calculated margin of exposure (MOE) greater than 100 for the repeated dose toxicity and developmental and reproductive toxicity endpoints.
Based on various study results, scientists present citral as a substance without concern for genotoxic potential, and the total systematic exposure to citral (7.2 μg/kg/day) is below the Threshold of Toxicological Concern (TTC) of 30 μg/kg/day for the repeated dose toxicity endpoint of a Cramer Class I material at the current level of use.
Citral was formally evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, and skin sensitization by RIFM. Data show it is not genotoxic, the MOE exceeds 100 for repeated dose and reproductive toxicity endpoints, and citral was assigned a No Expected Sensitization Induction Level (NESIL) of 1400 μg/cm² for the skin sensitization endpoint. Citral is not expected to be phototoxic or photoallergenic.
Skin sensitization was induced in 22 of 174 tests conducted with 1–5% pure citral in ethanol, but not with 0.5% citral in 82 test subjects. This confirms that citral is a concentration-dependent contact sensitizer. The maximum acceptable use limits calculated for citral using the dermal sensitization Quantitative Risk Assessment (QRA) developed by the International Fragrance Association (IFRA) are: 0.05% in deodorants, 0.6% in hydroalcoholic products for unshaved skin, 7% in liquid soaps, 8.2% in shampoos, and 100% in baby diapers and hand dishwashing.
As an α,β-unsaturated aldehyde, citral is attractive as a synthesis unit but tends to side reactions — for example, isomerizations — owing to its high reactivity. Citral is susceptible to oxidation and deterioration due to its conjugated double bonds and aldehyde groups. This reactivity underlies both its biological activity and its instability as a commercial ingredient.
Neral and geranial have an aldehyde in their structure — an electrophilic functional group that can react with amino residues of proteins, which is a motif ordinarily avoided in drug development due to the potential for undesirable effects and toxicity. Despite this, citral has acceptable drug-likeness properties and does not present any violations of Lipinski's rules, suggesting potential for drug development.
Citral, geranial, and neral are facing new EU restrictions (as of 2025), requiring brands to review formulations containing these compounds. This reflects growing regulatory attention to fragrance allergens in cosmetic and personal care products.
Further investigations should be carried out to expand knowledge of efficacy and toxicological studies in validating traditional uses of citral-bearing plants. The currently available body of scientific evidence for neral as an isolated compound is predominantly preclinical (in vitro and animal model studies), and the vast majority of studies have examined citral as a mixture of its two isomers rather than evaluating neral and geranial separately. Human randomized controlled trials on neral as a dietary supplement are absent from the reviewed literature.
Health conditions that Neral may help support.
Body systems that Neral may help support.
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