Lime

Lime (Citrus × aurantiifolia): A Comprehensive Reference

1. Identity and Botanical Classification

Taxonomy and Nomenclature

Lime (Citrus aurantiifolia) is a plant belonging to the family Rutaceae and to the genus Citrus. The species is now recognized under the hybrid designation Citrus × aurantiifolia. It is a hybrid citrus fruit (Citrus micrantha × Citrus medica), also known as Mexican lime or West Indian lime. The accepted binomial is Citrus × aurantiifolia (Christm.) Swingle. It is commonly known as Lime, Key Lime, Mexican Lime, or Mexican Thornless Key Lime, and is a small evergreen tree found in tropical Asia. The specific epithet aurantiifolia is formed from the genitive of the Latin noun aurantium, meaning "of orange," and folia, which means "leaves."

Morphology

The tree grows up to 5 m tall and has dense and irregular branches, spiny twigs, small dark green leaves, and yellowish-white flowers. Showy flowers, purple-tinged when new and pale pink or white when mature, appear in springtime and late summer in axillary racemes composed of 1–7 flowers per raceme. The fruit is thin-skinned, juicy, very acid, and fragrant. The fruits are almost always picked when unripe (green), and are usually consumed before they reach the ripe state (yellow). The pulp is greenish-yellow and produces an acidic but very perfumed juice.

Geographic Origin and Distribution

C. aurantifolia is believed to have originated from Southeast Asia around 4000 BC and is native to the Indo-Malayan region. It was assumed to have been carried to North Africa and the Near East by the Arabs, and was taken by crusaders from Palestine to Mediterranean Europe. It was introduced to the Caribbean islands and Mexico by the Spaniards and readily became naturalized in the West Indies and Mexico. The fruit is widely used in the United States, Mexico, Southeast Asia, and Latin America, but is increasingly widespread all over the world.

Common Preparations and Forms

The fruit is eaten raw or cooked, used as flavouring, or made into jellies, juices, jams, or marmalades. In Persian cuisine it is dried and used in cooking. The peel is chopped and used to make a sweetmeat. The leaves are sometimes added to soups and used as a condiment in Javanese dishes. The essential oil obtained from the peel is widely used in the pharmaceutical and cosmetic industry for drugs, perfumes, soaps, and body lotions, as well as in the preparation of detergents and to flavor foods or drinks. The term "lime" is used for a variety of citrus fruits, including the Key lime (Citrus × aurantiifolia), Persian lime (Citrus × latifolia), Makrut lime (Citrus hystrix), finger lime (Citrus australasica), blood lime (hybrid), and desert lime, among others. Supplemental forms include freeze-dried lime powder, standardized extracts, essential oils, and fresh juice preparations.

2. Traditional and Historical Use

Southeast Asia, Ayurveda, and South Asian Traditions

In Pakistan, lime has long been used traditionally to treat hypertension, cough, headache, and sore throat, and also as an antiseptic, anthelmintic, antiarthritic tonic, astringent, diuretic, and appetite stimulant. The fruit and other parts of the plant are used in Ayurveda, Siddha, and many other folk systems for the cure of different ailments. Traditionally in Ayurveda, the zest, juice, and leaves have been used — zest for carminative preparations, juice for pranayama-enhancing drinks, and leaves in topical pastes for skin irritations.

Middle East and Persian Traditions

In Persian culture, dried limes are used for cooking and in remedies for headaches and colds. Arab traders are credited with disseminating lime from Southeast Asia to the Middle East and North Africa, where it was incorporated into regional cuisines and herbal pharmacopeias.

West Africa

Lime in its natural state is widely used in West Africa, particularly in Nigeria, where it is very much employed in herbal medicine. Different forms of the fruit are used locally — juice of the fruit, burnt rind of the fruit (commonly known as "epa-ijebu" in the Yoruba dialect), and oil obtained from steam distillation. The plant is used in traditional medicine as an antiseptic, antiviral, antifungal, anthelmintic, astringent, diuretic, and mosquito bite repellent, and for the treatment of stomach ailments, constipation, headache, arthritis, colds, coughs, and sore throats, and used as an appetite stimulant.

Ethiopia and East Africa

Lime has been used for the treatment of hypertension by the people in Enderta, Northern Ethiopia, and Edo State, Nigeria.

Traditional Medicinal Uses Across Plant Parts

Medicinally, various plant parts of lime are used. The leaves are infused and taken orally for headaches and colds. The juice is also used in the treatment of snakebites, wounds, and dandruff. The root is used for haemorrhages and venereal disease. Due to the biological activity of its secondary metabolites, lime and its components are used in traditional medicine for treating joint diseases, headaches, coughs, cardiovascular disorders, and hemorrhoids.

Scurvy Prevention in Maritime History

Lime has been valued for its medicinal properties for centuries. The fruit is rich in vitamin C, aiding in the prevention of scurvy — a discovery pivotal to sailors during the Age of Exploration. The provision of lime juice to British Royal Navy sailors became a celebrated preventive measure against scurvy, and gave rise to the enduring slang term "limey" for British sailors.

Traditional Use Against Cholera

Among the citrus-based therapeutic uses recorded in the literature is the use of lime juice with honey as a cough reliever, and the use of orange, lime, and lemon juices as remedies for the prevention of kidney stone formation. The protective activity of lime juice against cholera was suggested in a case-control study from Guinea-Bissau.

3. Key Constituents and Active Compounds

Overview of Phytochemical Classes

The secondary metabolites of C. aurantifolia include alkaloids, carotenoids, coumarins, essential oils, flavonoids, phenolic acids, and triterpenoids. The other important constituents are apigenin, hesperetin, kaempferol, limonoids, quercetin, naringenin, nobiletin, and rutin, all of which contribute to its remedial properties.

Essential Oil Constituents

GC/MS analysis identified 60 volatile compounds in lime essential oil (LEO), of which the predominant constituents were limonene, γ-terpinene, and β-pinene. In fruit peel oils, limonene was the major volatile component, followed by terpinene, pinene, and sabinene. For leaf oils, limonene, pinene, and sabinene were the major components, followed by citronellal, geranial, linalool, and neral. One Italian analysis reported the fruit essential oils of C. aurantifolia as limonene (59%), β-pinene (16%), γ-terpinene (9%), and citral (5%). D-limonene has been identified as the major constituent of lime peel oil, recorded at 49.11% in Thai and 42.32% in South African specimens by GC-MS analysis.

Flavonoids and Polyphenols

Citrus fruits are a rich source of many flavonoids, especially flavanone glycosides (rutin, hesperidin, hesperetin, and quercetin) and polymethoxyflavones (nobiletin and tangeretin), which contribute to protection against atherogenesis. C. aurantifolia contains active flavonoids including apigenin, hesperetin, kaempferol, nobiletin, quercetin, and rutin, as well as flavones, flavanones, naringenin, triterpenoids, and limonoids.

Limonoids

Key active components identified by HPLC in lime juice include rutin, neohesperidin, hesperidin, and hesperetin. The limonoids identified include limonexic acid, isolimonexic acid, and limonin. LC-qTOF/MS analysis of lime peel ethanolic extract demonstrated at least 62 components, including compounds in the glycoside, saccharide, amino acid, organic acid, alkaloid, flavonoid, flavonoid glycoside, furanocoumarin, and terpenoid (limonoids) groups. The major components identified included 7-methoxy-coumarin, 5,7-dimethoxycoumarin, bergaptol, bergamotin, limonin, hesperidin, and neohesperidin.

Organic Acids

Lime juice contains approximately 47 grams per litre of citric acid — roughly twice that of grapefruit juice and five times that of orange juice. Lime juice resembles lemon juice in its content of citric acid (approximately 8%), but contains much less ascorbic acid (vitamin C) than lemon.

Furanocoumarins

Analytical measurement by gas chromatography and HPLC demonstrated that the rind of lime contains 6- to 182-fold concentrations of all furanocoumarins measured compared with the pulp. Bergapten was the most abundant substance in the rind. These compounds — which include psoralen, xanthotoxin, bergapten, isopimpinellin, and bergamottin — are toxicologically relevant and are discussed under Safety Considerations.

Mechanisms of Action

Citrus essential oils are particularly rich in monoterpenes such as d-limonene, β-pinene, and myrcene, which exhibit potent cytotoxic, antiproliferative, and pro-apoptotic effects against various human cancer cell lines. Emerging evidence suggests that these compounds can modulate multiple molecular targets involved in apoptosis, oxidative stress, and tumor progression.

The prolonged use of glucose produces free radicals and reactive oxygen species, which are primary drivers of high blood pressure. Antioxidants are known for reducing reactive oxygen species. The juice of Citrus aurantifolia has been reported to be rich in ascorbic acid and flavonoids and has displayed antioxidant activity. In experimental models, the fruit extract may reduce glucose-induced hypertension because of its antioxidant activity by reducing reactive oxygen species.

Citrus flavonoids and coumarins exhibit diverse biological functions, including antidiabetic, antimicrobial, antifungal, hypotensive, antioxidant, carminative, antibacterial, larvicidal, antiviral, uricosuric, antiyeast, antihepatotoxic, and antimutagenic activities. Additionally, they demonstrate significant anticancer, cardiovascular-protective, and neuroprotective properties.

Urinary citrate is a potent inhibitor of urinary crystallization that is freely filtered in the proximal tubule of the kidney — providing a direct mechanistic rationale for the use of lime juice in the management of urolithiasis through urine alkalinization and increased citraturia.

4. Scientific Evidence by Area of Use

4.1 Urolithiasis (Kidney Stones)

Small prospective clinical studies have found that orange, grapefruit, and lemon juices all increased urinary citrate levels. Only orange and grapefruit juices had an alkalinizing effect, while lemon juice showed a protective effect by raising urinary citrate levels. One study showed that urinary citrate increased after 4 hours of ingestion to 0.29 ± 0.21 vs. baseline of 0.15 ± 0.12 mg/mg creatinine in the lime group.

A prospective, cross-over, single-centre clinical study in 50 healthy medical student volunteers investigated the effect of citrate supplementation with fresh lime juice on urinary pH and calcium excretion compared with mist potassium citrate. One arm was prescribed potassium citrate while the other arm received citrate supplementation with a home preparation of fresh lime juice. Urinary pH and calcium-to-creatinine ratio (uCa/uCr) were measured at baseline and after 7 days of treatment.

Clinical trials have been conducted for the treatment of kidney stones through alkalinization of urine. A clinical trial for the treatment of kidney stones in 50 people using lime juice showed no efficacy.

A more recent and robust trial reported substantially different findings. A multicenter, double-blind, randomized controlled trial aimed to evaluate the efficacy and safety of a novel lime-based preparation called LPR (lime-based phytochemical-rich regimen) in preventing kidney stone recurrence over 24 months. In this double-blind, randomized, placebo-controlled, multicenter trial, 173 patients with calcium oxalate urolithiasis who had undergone successful stone removal were enrolled. LPR, a lime-based supplement rich in citrate and flavonoids, significantly reduced the 2-year recurrence rate of calcium oxalate stones by approximately 76%. This effect may be mediated by increased urinary citrate excretion, alkalinization, and attenuation of renal inflammation, as evidenced by reduced urinary IL-8 and proteinuria. LPR was well tolerated, with minimal adverse effects, and may serve as a safe, cost-effective adjunct for secondary prevention in patients intolerant to conventional alkali therapy. The standardized lime-based preparation used in this trial contained approximately 55 mEq of citrate content, combining freeze-dried lime powder and lime beverage.

Evidence strength: A small crossover trial showed null results for urinary pH or calcium reduction from raw lime juice alone; however, a 173-patient multicenter RCT using a standardized freeze-dried lime preparation showed significant reduction in stone recurrence. Caution is warranted in generalizing raw juice data to standardized preparations. The flavonoid content of the lime preparation may contribute to protective effects, but its role remains hypothesis-generating and requires further validation in human studies.

4.2 Antimicrobial Activity

Researchers investigated the potency of Citrus aurantifolia (lime fruit) against pathogens, in the different forms in which this fruit is used locally — juice of the fruit, burnt rind of the fruit (commonly known as "epa-ijebu" in the Yoruba dialect), and the oil obtained from steam distillation. The antimicrobial activity of "epa-ijebu" in different solvents was also compared.

Juice concentrates of Citrus aurantifolia (lime) were evaluated for antimicrobial activity against five bacterial and three fungal strains. Results revealed the presence of alkaloids, flavonoids, steroids, terpenoids, saponins, cardiac glycosides, and reducing sugars.

A 2025 study investigated the chemical compositions and antimicrobial activities of C. aurantifolia peel oils from Thailand and South Africa against five oral pathogens: Lactobacillus acidophilus, Streptococcus mutans, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Candida albicans. Antimicrobial activity was evaluated by broth microdilution. Thai lime oil exhibited the strongest activity (MIC and MBC/MFC values between 0.20 and 25.0 mg/mL), followed by South African lime (0.39–50.0 mg/mL).

In a 2025 bioprospecting study, the Rodriguan lime extract had the lowest overall minimum inhibitory concentration (MIC) of 5–10 mg/mL against Staphylococcus aureus, Salmonella enterica, Listeria monocytogenes, Bacillus cereus, and Lactobacillus plantarum.

The protective activity of lime juice against cholera was suggested in a case-control study from Guinea-Bissau, prompting investigation of the vibriocidal properties of juice from Citrus aurantifolia fruits.

Evidence strength: The antimicrobial activity of lime extracts and essential oils is well-documented in in vitro studies across multiple pathogens. Human clinical evidence remains limited, with the cholera data resting on an observational case-control study rather than a controlled trial.

4.3 Antioxidant Activity

Lime essential oil was measured according to the DPPH assay and ABTS assay, with IC₅₀ values of 2.36 mg/mL and 0.26 mg/mL, respectively. The chloroform extract of freeze-dried lime juice showed the highest radical-scavenging activity of 85.4% and 90% by the DPPH and ABTS methods at 624 μg/mL. Antioxidant activity was found to be proportionate to the content of flavonoids.

In vitro analysis revealed good inhibition of elastase and collagenase enzymes by fresh key lime essential oil, with IC₅₀ values of 145.02 and 63.97 μg/mL, respectively. The fresh key lime oil demonstrated stronger antioxidant activity (37.76 ± 0.80 μM Trolox equivalent/g) compared to dry key lime oil (27.76 ± 1.11 μM TE/g), suggesting that it retains more bioactive compounds.

Evidence strength: Antioxidant effects are robustly demonstrated in vitro. Human clinical data directly attributing health outcomes to lime's antioxidant activity remain sparse.

4.4 Lipid Metabolism and Cardiovascular Effects

A study explored the protective effects of lime essential oil (LEO) against lipid-induced hyperlipidemia in a rat model. Two groups of rats received oral LEO in doses of 0.74 g/100 g and 2.23 g/100 g with their diets. Eight weeks later, administration of LEO improved serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels in hyperlipidemic rats. Simultaneously, the LEO improved the health of the rats in terms of obesity, atherogenic index, and fatty liver.

In animal hypotensive studies, extracts of Citrus aurantifolia fruit exhibited a concentration-dependent reduction in systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate.

Evidence strength: Lipid-lowering and blood pressure effects are demonstrated primarily in animal models. No dedicated human clinical trials have assessed these endpoints for lime specifically. The cardiovascular data are preclinical and should be characterized as preliminary.

4.5 Anticancer Activity

Lime is one of the major citrus fruits widely consumed, but evidence about its health-promoting properties is limited. An investigation was conducted to understand the chemopreventive effects of lime juice on pancreatic cancer cells and the possible mechanism for induction of apoptosis using Panc-28 cells. All extracts of lime juice inhibited Panc-28 cancer cell growth. The MeOH extract exhibited maximum activity, with an IC₅₀ value of 81.20 μg/mL after 72 h. Inhibition of Panc-28 cells was in the range of 73–89% at 100 μg/mL at 96 h. The involvement of apoptosis in induction of cytotoxicity was confirmed by expression of Bax, Bcl-2, caspase-3, and p53.

Lime peel extract has the potential to inhibit cell proliferation and induce apoptosis of p53-mutated liver cancer cells (PLC/PRF/5). The non-toxic dose of hesperidin, limonin, and lime peel extract can inhibit the invasion abilities of PLC/PRF/5 cells.

Lime (C. aurantiifolia) has been studied for its effect against carcinogenesis through mechanisms such as arresting the mobility of cancer cells in the circulatory system, inhibiting metastasis, blocking angiogenesis, and inducing the tumour suppressor gene and apoptosis.

Evidence strength: Anticancer activity is supported exclusively by in vitro cell-line experiments and preclinical models. No human clinical trials have been conducted. No clinical trials have shown significant functional properties for lime as an anticancer agent.

4.6 Hypolipidemic and Body Composition Effects

A clinical trial conducted on 60 children aged 10–18 with a BMI above the 85th percentile using citrus fruit peels showed no efficacy in decreasing BMI, LDL-C, or blood pressure. Evidence from broader citrus meta-analyses indicates possible modest effects on body weight parameters, but these data pool multiple citrus species and cannot be attributed specifically to lime.

4.7 Anti-inflammatory Activity

Citrus species, including C. aurantiifolia, are rich in flavonoids, polymethoxylated flavones (PMFs), limonoids, carotenoids, and essential oils, each contributing to therapeutic effects such as antioxidant, anti-inflammatory, anticarcinogenic, and neuroprotective activities. Anti-inflammatory mechanisms documented preclinically include modulation of reactive oxygen species, inhibition of inflammatory cytokines, and inhibition of elastase and collagenase. All evidence is preclinical (in vitro or animal); no human RCTs have specifically targeted the anti-inflammatory properties of lime.

5. Body Systems and Health Areas of Association

• Renal / Urinary System: Lime is used for the treatment of urolithiasis. The citrate content of lime juice may inhibit calcium oxalate crystallization.
• Cardiovascular System: Traditional and phytochemical literature describes antihypertensive and anti-lipidemia activities.
• Gastrointestinal System: Lime is used traditionally for stomach ailments and constipation, and as an appetite stimulant.
• Immune / Antimicrobial: It is widely used because of its antibacterial, antifungal, and antiviral properties.
• Hepatic System: Lime has been investigated for hepatic protection.
• Skeletal System: Lime has been investigated for its potential role in osteoporosis.
• Oncology: In vitro and preclinical investigations in pancreatic, colon, and liver cancer cell lines have been published; human evidence is absent.
• Skin: Topical use and phototoxic risk are both associated with lime, as discussed under Safety Considerations.

6. Dosage Forms and Dosages Reported in Studies

No universally accepted therapeutic dosage has been established for lime as a dietary supplement. There is not enough scientific information to determine an appropriate range of doses for lime. The following dosages have been reported in specific studies:

• In a rat model of hyperlipidemia, oral lime essential oil was administered at doses of 0.74 g/100 g and 2.23 g/100 g body weight with diet over eight weeks.
• In a crossover human clinical trial comparing lime juice to potassium citrate in 50 healthy volunteers, one arm received a home preparation of fresh lime juice as a citrate supplementation source for 7 days.
• In the multicenter RCT on kidney stone recurrence, the standardized lime-based phytochemical-rich regimen (LPR) contained approximately 55 mEq of citrate content, combining freeze-dried lime powder and lime beverage.
• In in vitro pancreatic cancer cell studies, the methanol extract of lime juice showed an IC₅₀ value of 81.20 μg/mL after 72 h, with inhibition of Panc-28 cells in the range of 73–89% at 100 μg/mL at 96 h.
• For antimicrobial activity against oral pathogens in vitro, Thai lime peel oil exhibited MIC and MBC/MFC values between 0.20 and 25.0 mg/mL.

7. Safety Considerations and Known Interactions

Phytophotodermatitis

Phytophotodermatitis is a phototoxic inflammatory reaction of the skin resulting from contact with a light-sensitizing botanical agent (such as lime juice) followed by exposure to ultraviolet A (UV-A) light. Symptoms include erythema, edema, blisters (vesicles and/or bullae), and delayed hyperpigmentation. Heat and moisture tend to exacerbate the reaction. Phytophotodermatitis is not an immunologic response; no prior exposure to the photosensitizing agent is required.

Phytophotodermatitis is a nonimmunologic phototoxic cutaneous eruption resulting from contact with photosensitizing substances found in plants; furocoumarins present in limes are typically implicated and become activated following exposure to sunlight, especially ultraviolet A rays (320–400 nm). Two types of toxic reactions occur: one is oxygen-independent, in which the ultraviolet-activated furocoumarins bind to RNA and nuclear DNA; another is oxygen-dependent, where induced furocoumarins cause cell membrane damage and edema. These reactions ultimately lead to cell death.

The rind of lime contains 6- to 182-fold concentrations of all furanocoumarins measured compared with the pulp. Bergapten was the most abundant substance in the rind. Hydration of the skin during the preparation of limeade, combined with increased levels of bergapten in local limes, can produce a dramatic bullous reaction.

Plants like Citrus × aurantiifolia (lime) have garnered attention for their ability to induce severe skin phototoxic reactions in individuals. Children are particularly susceptible to phytophotodermatitis due to recreational exposure in nature, with psoralen-containing plants being a common cause of phototoxic dermatitis in this age group.

CYP3A4 Enzyme Inhibition and Drug Interactions

Bergamottin and 6′,7′-dihydroxybergamottin (furanocoumarins also found in lime) are responsible for the "grapefruit juice effect," in which these furanocoumarins affect certain P450 liver and gut enzymes, including inhibition of CYP3A4, which either activates or deactivates many drugs, leading to higher or lower levels in the bloodstream.

The furanocoumarin derivatives in lime juice can reversibly and irreversibly inhibit CYP3A in the gut mucosa. When lime juice and certain drugs are taken together orally, this leads to effects on their presystemic extraction (first-pass metabolism). Consequently, presystemic extraction of the drug is reduced, and more of the drug reaches the circulation over time. With this increased systemic exposure to the drug, there is an increased drug effect. Published research has specifically examined lime juice alongside digoxin in in vitro Caco-2 cell transport studies.

Furanocoumarin ingestion and subsequent exposure to ultraviolet light have been reported to cause photosensitive dermatitis. In addition, furanocoumarins inhibit the drug-metabolizing enzyme CYP3A in the liver, which can prolong the half-life of drugs metabolized by this pathway.

Dental Enamel Erosion

Limes contain a high amount of citric acid, meaning that overconsumption can erode the enamel on teeth and cause increased sensitivity.

Gastrointestinal Effects

Consumption of large amounts of lime juice may lead to digestive issues like heartburn or stomach discomfort due to its high acidity.

Advanced Kidney Disease Caution

In accordance with clinical guideline recommendations, caution should be exercised in patients with advanced chronic kidney disease, particularly due to the potassium content of lime-based supplements.

Photosensitivity from Oral Ingestion

Oral administration of furanocoumarins may also be phototoxic. Furanocoumarin ingestion and subsequent exposure to ultraviolet light have been reported to cause photosensitive dermatitis.

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