Citron

Other Names

Ağaç kavunubalangbeejora-nimbubijorabimiroBuddha's handcedratcédratCedrátcédratiercedratocedriolacedrocedro limóncidracidralcidraocidreracidrerocidroCitron à parfumcitron fruitCitronaCitronasCitronnier des JuifsCitrus acidaCitrus alataCitrus aureaCitrus balotinaCitrus bicolorCitrus bigenaCitrus cedraCitrus cedrataCitrus kwangsiensisCitrus medicaCitrus medica L.Citrus medica subsp. bajoumCitrus medica var. alataCitrus medica var. nanaCitrus medica var. odorataCitrus medica var. properCitrus medica var. sarcodactylisCitrus medica var. tarungCitrus medica var. tuberosaCitrus medica var. yunnanensisCitrus nanaCitrus pyriformisCitrus × aurantium var. medicaCytronesregesrogetrogfat shaufingered citronfingered lemonfo shoufoot sowfu shoufu shou huafuh chau hwafuh shaujeruk sukadejora tengakabbadkitrolimau susulimón cidramahalumahalungMalus Medicamanao riponmanao-khwaimaru-bushukanmatulungaponcidreponcilRimo AntuRimo Telur Buayashouk-ta-kwahsitrunsom-musomma-nguasuccadeSukaattisitruunaSukatcitronthanh yêntoranjturunjvëëxxiang yuanZitronatzitrone枸櫞

Synopsis

Citron (Citrus medica L.): A Comprehensive Reference

1. Identity, Taxonomy, and Botanical Description

Scientific name: Citrus medica L. (Linnaeus, 1753). Citrus medica Linn., also called "cedar," "citron," "etrog," "foshou," and "fingered citron," belongs to the Rutaceae family and is one of the three basic species of the genus Citrus, together with Citrus maxima Burm. (pomelo) and Citrus reticulata Blanco (mandarin).

Linnaeus's use of "medica" in the species epithet does not refer to the plant's medicinal use but rather its association with the classical empires of Persia and Media. Common names across languages include cédrat (French), etrog (Hebrew), and cedro (Italian).

It is a short, medium-sized evergreen tree that reaches 4–8 metres in height. Citrus medica L. is formed by a slow-growing shrub or small tree reaching 8–15 ft (2.5–4.4 m) high, with rigid branches, rigid shoots, and short or long needles in the leaf axils. Unlike modern citrus varieties such as lemons or oranges, the citron fruit is notable for its thick, aromatic rind and relatively dry pulp.

1.1 Cultivar Groups and Notable Varieties

Citron cultivars are broadly divided into two groups:

Acid cultivars, which have pinkish floral buds and shoots, acid pulp, and a dark inner seed coat and chalazal spot.
Non-acid cultivars, which are without pinkish floral buds and shoots, with non-acid pulp, a colourless inner seed coat, and a pale-yellow chalazal spot.

In China, Japan, Indo-China, and India, Citrus medica L. var. Sarcodactylis (Noot.) Swingle is widely cultivated. It is the fingered citron or Buddha's Hand Citron, whose fruit is split into a number of finger-like sections, without or with very scanty pulp.

1.2 Geographic Origin and Distribution

Native to the lower Himalayan foothills and widely cultivated in Asia and the Mediterranean since antiquity, citrons have played a crucial role in culinary traditions, religious rituals, herbal medicine, and perfumery. Citron, native to Southeast Asia, was imported to the Mediterranean around 300 B.C. It is also cultivated in Japan, China, Bangladesh, Arabia, and Australia, and is available seasonally from October to January.

1.3 Common Preparations and Commercial Forms

With a distinct lemony fragrance, citrons are used to make candied peels, citron tea, citron juice, and infused spirits such as citron vodka. Citrus medica is used in making alcoholic beverages, syrup, candied peels, jams, carbonated drinks, marmalade, and other value-added products; pectin obtained from the fruits can be used for food thickening, baking, jellies, low-calorie foods, and various pharmaceutical applications. Citrus essential oils (EOs) are obtained mainly from the fruit rind (flavedo), but also from leaves and flowers, using hydro-distillation (mainly in Clevenger-type apparatus) or cold-pressing extraction from the peel.

2. Historical and Traditional Use

2.1 Ancient History

The Egyptologist and archaeologist Victor Loret identified citron depicted on the walls of the botanical garden at the Karnak Temple, dating back to the time of Thutmosis III, approximately 3,500 years ago. Citron was also cultivated in Sumer as early as the 3rd millennium BC.

2.2 Jewish Tradition

The citron (the word for which in Hebrew is etrog) is used by Jews for a religious ritual during the Jewish harvest holiday of Sukkot, the Feast of Tabernacles; therefore, it is considered to be a Jewish symbol, one found on various Hebrew antiques and archaeological findings. According to Jewish Rabbinical tradition, the "fruit of the tree hadar" refers to the citron. The Mishna Sukkah, dated to approximately the 2nd century AD, deals with halakhic aspects of the citron. The etrog fruit can command as much as US$100 per fruit, depending on quality.

2.3 Ayurvedic and Indian Traditional Medicine

Known as "Bijapura" in Ayurvedic literature, Citrus medica L. is a member of the Rutaceae family; several parts of citron are generally used in the Indian traditional system of medicine. Leaves carry anthelmintic and estrogenic activities; the fruit has analgesic, anticancer, and antiulcer activities; peel carries many characteristics including hypoglycemic, anti-cholinesterase, hypocholesterolemic, hypolipidemic, antimicrobial, and anthelmintic properties; seeds have antidiabetic, hypocholesterolemic, hypolipidemic, and estrogenic activities. The species is widely used in Ayurvedic medicine for antioxidant, carminative, antibacterial, anticancer, and antiviral purposes.

2.4 Traditional Chinese Medicine

Citron oil is widely used in Persian folk medicine for musculoskeletal, gastrointestinal, and nervous ailments. Ethno-medicinal uses of citron are well-exploited in traditional medicinal systems including Jewish medicine, Ayurveda, and Chinese traditional medicine, to treat nausea, excessive thirst, skin disease, acne, and difficulties in childbirth, among other health issues.

2.5 Mediterranean and European Traditional Use

In past times, citrons have also been employed in traditional medicine as an anti-infective, an anti-inflammatory, and to treat digestive disorders. Fruits and leaves are used in different countries in the treatment of allergic inflammation, for treating colds, as a decongestant, an expectorant, and a carminative, or, in the case of pathologies of the intestinal tract and rectum, as a stomachic, an antispasmodic, a diuretic, and a digestive. The fresh shoots, leaves, flowers, fruits, and seeds of citron have all entered into a number of traditional medicinal preparations for the treatment of asthma, arthritis, headache, stomach-ache, intestinal parasites, and certain psychological disturbances.

2.6 Perfumery

The citron essential oils are used for flavoring, for perfuming, in fruit beverages, in soft drinks, in cosmetics, and in household products. Citron essential oil (cedrate oil) has been used for centuries in fine perfumes for its sweet, citrusy scent.

3. Phytochemical Composition: Key Constituents

Citrus medica Linn., belonging to the Rutaceae family, has been used for centuries in medicine for its antioxidant, anti-inflammatory, antimicrobial, antiviral, and antihyperglycemic properties. These activities are ascribable not only to the presence of health-promoting macronutrients and micronutrients such as carbohydrates, minerals, amino acids, and vitamins, but also to specialized metabolites, such as flavonoids (apigenin, hesperetin, hesperidin, naringin, naringenin, rutin, quercetin, and diosmin), coumarins (citropten, scoparone, and bergapten), terpenes (limonene, γ-terpinene, limonin, and nomilin), and phenolic acids (p-coumaric acid, trans-ferulic acid, and chlorogenic acid).

3.1 Flavonoids

Citrus fruits contain a substantial amount of flavanone-7-O-glycosides (e.g., naringin, eriocitrin, hesperidin, and narirutin), flavones (e.g., rhoifolin, vitexin, diosmin), polymethoxylated flavones (PMFs, e.g., nobiletin, tangeritin, and 5-demethyl nobiletin), flavonols (quercetin, rutin, and kaempferol), and anthocyanins (cyanidin and peonidin glucosides). Flavanones and flavanols were the primary flavonoids in the pulp, peel, and seeds of citron, with total flavonoid concentration ranging from approximately 9 µg/g fresh weight in seeds to 508 µg/g fresh weight in the pulp.

3.2 Essential Oil and Terpenes

Volatile and semi-volatile constituents represent about 85–99% of the citrus oil fraction, usually consisting of over 200 compounds. Major bioactive compounds present in citron are iso-limonene, citral, limonene, phenolics, flavonones, vitamin C, pectin, linalool, decanal, and nonanal, accounting for several health benefits. Among the many biological properties of C. medica, its antimicrobial properties are undoubtedly among the most heavily investigated, probably due to the strong presence of phytochemicals such as citral, linalool, and limonene, which are endowed with antimicrobial effects.

3.3 Limonoids

Citrus limonoids (limonexic acid, limonin, and nomilin) have been shown in in vitro studies to induce apoptosis and inhibit the proliferation (IC50 values <50 μM after 72 h) of pancreatic cancer cells (Panc-28) by enhanced cleavage of caspase-3, decreased mitochondrial membrane potential, and upregulation of Bax/Bcl-2 protein expression. Moreover, in these studies, limonoids upregulated the expression of cyclin-dependent kinase inhibitor (p21) and exhibited anti-inflammatory activity through downregulating proinflammatory proteins Cox-2, NF-κB, and IL-6.

3.4 Coumarins and Furanocoumarins

Botanicals such as citrus are composed of hundreds of constituents, some of which have the potential to cause toxic effects; for example, bergapten (also known as 5-methoxypsoralen or 5-MOP) is a naturally-occurring, phototoxic furanocoumarin in citrus peel oils. Furanocoumarin monomers and dimers such as paradisins are known to inhibit cytochrome P450 from different families. Notably, interactions between furanocoumarins and human CYP3A4, a cytochrome P450 found in intestinal enterocytes and liver hepatocytes, have generated concern because this enzyme represents half of all human P450 enzyme pools and plays a major role in the metabolism of drugs altered by oxidation.

3.5 Pectin and Dietary Fiber

Pectin and heteropolysaccharides play a major role in citron as dietary fibers. Citrus medica L. (citron) is a citrus fruit known for its uses in cooking and traditional medicine, including its application in vegetable soups and cookies, as well as its juice for treating nausea and hypertension.

3.6 Macronutrients and Micronutrients

Etrog (citron) fruit is rich in fats, sugars, fibres, macronutrients (vitamin C, calcium, potassium, magnesium, iron, phosphorus, and thiamine), and micronutrients (riboflavin, niacin, copper, manganese, zinc, chromium, and others). The fruits are also rich in essential oils (terpenes), carotenoids, alkaloids, flavonoids, pectin, mucilage, sterols, glycosides, and other phytoconstituents.

3.7 Distribution of Phenolic Compounds Across Fruit Parts

A 2024 study published in Molecules found that the albedo and seeds had significantly lower antioxidant activity coefficient (AAC) values, while the green and yellow flavedo showed noteworthy results. O-coumaric acid was the predominant phenolic acid in all citron fractions, found in the highest concentration in the albedo at 37.54 µg/g fresh weight. The pulp had a substantially higher antioxidant activity coefficient (AAC) of 168.2 compared to other parts; the albedo and seeds had significantly lower AAC values, while the flavedo showed noteworthy results.

4. Mechanisms of Action

4.1 Antioxidant Mechanisms

In vitro models such as the beta-carotene–linoleic acid, DPPH, superoxide, and hamster LDL oxidation methods have been used to measure the antioxidant activity of citrus bioactive compounds including limonoids, flavonoids, and coumarins. In general, flavonoids containing a chromanol ring system demonstrated stronger antioxidant activity compared to limonoids and bergapten, which lack hydroxy groups; several structural features were linked to the strong antioxidant activity of citrus flavonoids.

4.2 Anti-inflammatory Mechanisms

Studies have focused on structure-activity relationships and cellular targets in citrus including the PI3K/Akt/mTOR, Nrf2/Keap1, and NF-κB signaling axes. An in vitro study on d-limonene activity revealed an increase in the IL-10/IL-2 ratio, enhancing IL-10 levels — a cytokine synthesis inhibitory factor that inhibits proinflammatory Th1 cytokine production. Furthermore, d-limonene epoxide has been observed to prevent the release of inflammatory mediators, inhibit vascular permeability, reduce migration of neutrophils, and display systemic and peripheral analgesic effects via the brain's opioid system.

4.3 Neuroprotective Mechanisms

Limonene, one of the main components of the genus Citrus, has been studied for neuroprotective effects against the neurotoxicity elicited by Aβ1-42 oligomers, considered a triggering factor in Alzheimer's disease. Assessments using acetylcholinesterase activity (Ellman's colorimetric method), mitochondrial dehydrogenase (MTT assay), and reactive oxygen species generation found that the monoterpene limonene showed specific activity against acetylcholinesterase with an IC50 almost comparable to that of galantamine, used as a positive control.

Treatments with limonene significantly influenced ADCY1 expression; high concentrations increased ADCY1 expression while low concentrations reduced it. Limonene demonstrated several biological properties including anti-inflammatory, antioxidant, anti-cancer, and anti-nociceptive activities. Several studies also demonstrated a promising neuroprotective role of limonene in neurodegenerative diseases; the abundance of limonene in different plant species, its safety profile, and its mechanisms of action make this compound a potentially favourable agent for treating neurodegenerative diseases.

4.4 Antidiabetic Mechanisms

Citron contains chemical compounds such as umbelliferone, scopoletin, and limonin, and has been shown to increase insulin secretion in animal studies. Synthesizing data from preclinical and early-phase clinical research on d-limonene, investigators have explored its molecular mechanisms ranging from reactive oxygen species mitigation and apoptosis induction to metabolic remodeling and neurotransmitter modulation; special attention has been given to its capacity to ameliorate pathophysiological hallmarks of diabetes and neurodegeneration.

4.5 Antimicrobial Mechanisms

Limonene was found to reduce LPS-induced neuroinflammatory responses in mice, as evidenced by decreased GFAP and IBA-1 levels, along with suppressed expression of inflammatory cytokines. Limonene has shown therapeutic effects in gastric and airway inflammation, reducing the expression of IL-1, IL-6, TNF-α, and NF-κB.

5. Scientific Evidence by Area of Use

5.1 Antioxidant Activity

The antioxidant properties of C. medica are among the most extensively characterized in vitro. A 2024 study published in Molecules aimed to evaluate the antioxidant capacity and characterize the phenolic compounds present in the peels (including flavedo and albedo), pulp, and seeds of citron. Results showed that the pulp had a substantially higher Antioxidant Activity Coefficient (AAC) of 168.2 compared to other parts; the albedo and the seeds had significantly lower AAC values, while the green and yellow flavedo showed noteworthy results. O-coumaric acid was the predominant phenolic acid in all citron fractions, found in the highest concentration in the albedo; flavanones and flavanols were the primary flavonoids, with total flavonoid concentration ranging from approximately 9 µg/g fresh weight in seeds to 508 µg/g fresh weight in the pulp.

Evidence strength: The antioxidant evidence for C. medica is largely in vitro (cell-free and cell-based assays). No well-powered randomized controlled human clinical trials on antioxidant endpoints specific to C. medica have been identified in the peer-reviewed literature reviewed here.

5.2 Antimicrobial Activity

The antimicrobial activity of citron EOs has been assayed against bacterial strains including Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Low concentrations of C. medica cv. 'Rugosa' EO showed an inhibitory effect on P. aeruginosa, and higher concentrations inhibited more B. cereus and E. coli than S. aureus. The antimicrobial activity registered confirmed the traditional uses of citron as a food-preserving agent.

C. medica var. Sarcodactylis EO was screened for antiviral activity against Avian influenza A virus (H5N1) using the Madin Darby canine kidney (MDCK) cell line. At a concentration of 0.5 µg/µL, the EO from leaves showed 95% inhibition, while the inhibition by the fruit EO was lower at 50%. According to studies on antiviral activity against H5N1, limonene, which is present in high quantities in citron EO, appears to be one of the main factors responsible for this activity.

Evidence strength: Antimicrobial evidence is predominantly in vitro. No controlled human clinical trials were identified for antimicrobial endpoints.

5.3 Anticancer / Cytotoxic Activity

Different studies have reported evidence that Citrus consumption is associated with a reduced cancer incidence. At the preclinical level, a study by Menichini and colleagues reported the chemical profile and photo-induced cytotoxic activity of Citrus bergamia and Citrus medica cv. 'Diamante'; both oils exhibited a selective inhibition of the A375 tumoral cell line.

The anticancer potential of citron has been documented, with studies confirming its ability to significantly inhibit cancer cell proliferation. However, all such studies identified in this review are in vitro or in animal models. No human clinical trials investigating anticancer effects of citron specifically have been identified.

Evidence strength: Preliminary; limited to in vitro and animal studies. Human evidence is absent.

5.4 Antidiabetic / Antihyperglycemic Activity

In recent years, particular attention has been focused on the antidiabetic activity of C. medica. Animal models have shown antidiabetic activity; citron contains chemical compounds such as umbelliferone, scopoletin, and limonin, and has been shown to increase insulin secretion in animal studies. Reviews of d-limonene, a principal constituent of citron EO, note that its biological versatility spans antidiabetic, neuroprotective, and gastroprotective domains, with molecular mechanisms ranging from reactive oxygen species mitigation to metabolic remodeling.

Evidence strength: Predominantly animal and in vitro. No dedicated randomized controlled trials in humans for citron's antidiabetic effects have been identified in the sources reviewed.

5.5 Neuroprotective Activity

Several studies demonstrated the promising neuroprotective role of limonene in neurodegenerative diseases; the abundance of limonene in different plant species, its safety profile, and its mechanisms of action make this compound a potentially favourable agent for treating neurodegenerative diseases. An in vitro study demonstrated that limonene showed specific anti-acetylcholinesterase activity with an IC50 comparable to galantamine in a model of Alzheimer's-related neurotoxicity (see Section 4.3). Alterations in ADCY1 expression following treatment with citron EO suggested a role for limonene in effects on the central nervous system.

A juice-extract syrup of C. medica also showed activity against migraines in one reported study. However, details on study design, sample size, and controls are limited in available secondary sources.

Evidence strength: Primarily in vitro and animal-based. Neuroprotective claims in humans remain to be established through well-designed clinical trials.

5.6 Anti-inflammatory and Analgesic Activity

Various types of biological activity documented for C. medica in the 2023 systematic review include anti-inflammatory and analgesic actions, among others. Preclinical evidence implicates NF-κB pathway inhibition and suppression of pro-inflammatory cytokines (IL-1, IL-6, TNF-α) as key mechanisms of limonene and other citron constituents.

Evidence strength: Mechanisms are characterized in cell and animal models. No confirmed large-scale human clinical trials specific to citron anti-inflammatory effects were identified.

5.7 Gastrointestinal Applications

The juice of C. medica has been used for treating nausea and hypertension in traditional contexts. Fruits and leaves are used in different countries as a stomachic, antispasmodic, diuretic, and digestive, and in the treatment of pathologies of the intestinal tract and rectum.

Evidence strength: Traditional use is well-documented. Scientific evidence is predominantly ethnobotanical and in vitro; controlled clinical studies are lacking.

6. Body Systems and Health Areas Associated with Citron

Digestive system: Carminative, stomachic, antispasmodic, and digestive actions are reported across traditions.
Cardiovascular system: The fruit has been associated with cardioprotective and antihypertensive properties in pharmacological studies.
Immune/Infection: The species is used in Ayurvedic medicine for antibacterial and antiviral purposes.
Endocrine/Metabolic: The peel carries hypoglycemic and hypolipidemic characteristics, and seeds have antidiabetic and hypocholesterolemic activities.
Central nervous system: Alterations in ADCY1 expression following citron EO treatment suggest a role for limonene in effects on the central nervous system.
Skin/Dermatology: Citron has been used in traditional medicine for skin diseases and acne.
Respiratory: Citron is used in different countries for treating colds, as a decongestant and expectorant.

7. Dosage Forms and Dosages Reported in Studies

No universal standardized dose for C. medica as a dietary supplement has been established by major regulatory or pharmacopeial bodies. The following dosages appear in scientific studies:

In an in vitro antiviral study, EO from citron leaves at a concentration of 0.5 µg/µL showed 95% inhibition of H5N1, while the fruit EO showed 50% inhibition at the same concentration.
In a study on the SH-SY5Y neuroblastoma cell line, C. medica cv. 'Liscia' and cv. 'Rugosa' EOs were evaluated at concentrations of 400, 200, 100, and 50 μg/mL for their influence on ADCY1 expression.
Citrus limonoids (limonexic acid, limonin, and nomilin) demonstrated induction of apoptosis and inhibition of proliferation of pancreatic cancer cells (Panc-28), with IC50 values <50 μM after 72 hours of treatment.
A low yield of oil obtained by steam distillation of citrus peel was reported at 0.64 ± 0.07 g of oil per gram of peel.
Essential oil extraction: Citrus EOs are obtained mainly from the fruit rind (flavedo), but also from leaves and flowers, using hydro-distillation in Clevenger-type apparatus or cold-pressing from the peel.

All above dosages are from experimental (non-clinical) in vitro or early in vivo studies. No human clinical dose-ranging studies for C. medica as an isolated supplement were identified in the reviewed peer-reviewed literature.

8. Safety Considerations and Interactions

8.1 Furanocoumarins and Phototoxicity

Bergapten (also known as 5-methoxypsoralen or 5-MOP) is a naturally occurring phototoxic furanocoumarin in citrus peel oils. These compounds are potential photosensitizers that can cause severe phytophotodermatitis after either skin contact or ingestion followed by UV sun exposure. This photosensitization property is a notable problem with citrus essential oils because they are extensively used in perfumes and cosmetics.

The International Fragrance Association (IFRA) guideline for citrus oils containing furanocoumarins states that, due to the phototoxicity of bergapten, citrus oils should not be used in "leave-on" products such that the concentration of bergapten exceeds 15 ppm. Because distilled citrus oils contain virtually no furanocoumarins, they are not phototoxic.

8.2 Drug Interactions via CYP450 Inhibition

Certain furanocoumarins, particularly bergamottin, can inhibit the cytochrome P450 enzyme system (specifically CYP3A4) in the intestines and liver. This can interfere with the metabolism of various medications, leading to elevated drug concentrations in the bloodstream and potentially serious side effects. Bergaptol, a furanocoumarin present in citrus, can inhibit the activities of cytochrome P450s, especially CYP2C9 and CYP3A4, thereby affecting the metabolism and concentrations of some drugs and toxins; compared with other coumarins, bergaptol has the least potency to inhibit CYP3A4 in cancer cells.

8.3 Skin Sensitization and Allergic Reactions

The essential oils of citron, especially when concentrated, can cause mild skin irritation or sensitivity in some individuals. Excessive consumption of the rind or essential oil is not recommended for those with citrus allergies or digestive sensitivity.

8.4 Evidence Limitations and Research Gaps

Although many studies have reported C. medica's chemical and biological properties, the literature had not previously been analyzed via a systematic approach until a 2023 review using PubMed and Scopus was performed to analyze chemical composition and biological properties. Existing research on specific constituents such as bergaptol has mostly been conducted in vitro; further in vivo and clinical studies are warranted to identify safe and effective doses for multimodal application. The overall body of scientific evidence for C. medica as a dietary supplement in humans remains at an early, primarily preclinical stage, and most biological activities identified to date derive from in vitro or animal models.

References

Health Conditions

Health conditions that Citron may help support.

No conditions available.

Body Systems

Body systems that Citron may help support.

No body systems available.