Lemon

Lemon (Citrus × limon, Rutaceae)

1. Identity, Taxonomy, and Natural Source

Botanical name: Citrus × limon is a species of small evergreen tree in the Citrus genus of the flowering plant family Rutaceae. The species designation Citrus limon (L.) Burm. f. is used interchangeably in the scientific literature with the hybrid designation Citrus × limon. A true lemon is a hybrid of the citron and the bitter orange, and its origins are uncertain, but some evidence suggests lemons originated during the 1st millennium BC in what is now northeastern India.

The tree reaches 2.5–3 m in height and has evergreen lanceolate leaves. Bisexual flowers are white with a purple tinge at the edges of the petals, gathered in small clusters or occurring individually in leaf axils. The fruit is an elongated, oval, pointed green berry that turns yellow during ripening, with juicy pulp divided into segments. The pericarp is made of a thin, wax-covered exocarp, under which there is the outer part of the mesocarp (flavedo), containing oil vesicles and carotenoid dyes.

The Citrus limon (L.) Burm., popularly known as the lemon tree, is a species from the Rutaceae family native to Asia. C. limon dominates the global market, but its production is limited to regions with warm and temperate climates due to its sensitivity to low temperatures; Spain leads production within the Mediterranean region, accounting for 42% of the total, followed by Italy (38%), Greece (5%), and Portugal (1.6%). In 2024, world production was 23 million tonnes, led by India and Mexico with 31% of the total.

Common names and linguistic etymology: The name "lemon" was first used during the Middle Ages, around 1300–1450 AD, believed to be a mix of the French word "limon" and the Italian term "limone," themselves derived from the Arabic "laymun" and the Persian "limun," terms used to refer to the yellow fruit popular in those countries for centuries.

1.1 Common Forms and Preparations

The fruit is primarily used for its juice, while the flesh and peel are used in various culinary applications. Additional preparations documented in the literature include:

• Fresh juice: The juice of the fruit is commonly used as a food ingredient in both commercial and home recipes, valued for its tart, tangy, and fresh character.
• Essential oil (cold-pressed peel): The exceptionally fragrant rind is a major source of commercial essential oil and aroma compounds.
• Peel/zest: Used dried or fresh; citrus flavonoids are present chiefly in glycoside or aglycone forms, and flavonoids are more abundant in the zest than in the seeds.
• Peel capsules/powder: 0.25–5 g of the peel per day in capsule form or drunk as a tea has been described in herbal practice references.
• Lemon juice powder: A dehydrated form of fresh lemon juice retaining key bioactive compounds such as citric acid, vitamin C, flavonoids, and essential oils, produced through drying processes designed to preserve its nutritional and functional properties.
• Lemonade (diluted juice): Used in nephrolithiasis studies; daily consumption of 120 mL of concentrated lemon juice (containing 5.9 g of citric acid) diluted in 2 L of water was the regimen studied in a small trial evaluating urinary metabolic parameters and stone formation.
• Tincture (peel): Ethanolic tinctures of the dried peel are available as dietary supplements, though clinical dosing data for this form are absent from peer-reviewed literature.

2. Traditional and Historical Use

Lemon juice has traditionally been used as an astringent, diaphoretic, diuretic, gargle, lotion, and tonic. The lemon may have been depicted in Roman artwork as early as the first century AD.

Its popularity grew as explorers and traders spread the fruit across the globe, with lemon trees eventually finding their way to the Americas during the age of European colonization. In addition to its culinary uses, lemon gained a reputation as a remedy for various ailments, such as the common cold and inflammatory conditions like gingivitis and stomatitis.

Scurvy and naval medicine: In 1747, Scottish physician James Lind performed one of the first clinical trials to test the theory that citrus juice could prevent and treat scurvy — a disease caused by vitamin C deficiency — in sailors on long voyages. Though the link between the disease and vitamins was not yet known (vitamin C, later named ascorbic acid, would not be identified until 1912), citrus fruits had been observed to improve outcomes in sailors. In the 1600s, physicians became aware that daily intake of lemon juice prevented outbreaks of scurvy among sailors on long sea voyages. English ships were required by law to carry enough lemon or lime juice for each sailor to receive 1 oz daily, earning them the nickname "limeys."

Medieval Arabic and Persian medicine: The medieval Arab physician Ibn Jumay devised a way of preserving lemons with salt and mentions the fruit's medicinal uses for a wide range of conditions. His writing was translated, and lemon's culinary and medicinal fame spread.

Ayurvedic and folk medicine: Lemon is one of the most widely consumed citrus fruits worldwide, valued for its distinctive flavor, high vitamin C content, and broad therapeutic applications; traditionally, it has been used in Ayurvedic and folk medicine for its depurative, antimicrobial, and digestive properties. Its use in traditional medicine is well known to treat scurvy, high blood pressure, common cold, and irregular menstruation.

South Asian traditional uses: In India and Nepal, ginger, lemon, and black salt mixture were used widely to treat nausea.

Antimicrobial applications in traditional practice: Lemon has a long history of use as a natural antimicrobial agent.

3. Key Constituents and Active Compounds

3.1 Overview of Phytochemical Classes

Lemon fruit is a rich source of nutrients and provides health benefits; lemons are an interesting source of flavonoids, vitamins, minerals, dietary fibers, essential oils, organic acids, and carotenoids.

The major phytochemicals include flavonoids (hesperidin, eriocitrin, and diosmin), limonoids (limonin and limonin glucoside), essential oils (limonene, citral, and citronellal), and phenolic acids (ferulic and p-coumaric acids).

3.2 Flavonoids

The valuable biological activity of C. limon is determined by its high content of phenolic compounds, mainly flavonoids (e.g., diosmin, hesperidin, limocitrin) and phenolic acids (e.g., ferulic, synapic, p-hydroxybenzoic acids). Lemon (Citrus limon) contains high levels of flavonoids, especially flavanones and flavone glycosides; flavonols, flavone aglycones, and polymethoxyflavones are also present but at lower concentrations.

The predominant flavanones identified in lemon juice extract are hesperidin and eriocitrin, above the flavones diosmetin-6,8-di-C-glucoside and diosmetin-8-C-glucoside. C. limon distinguishes itself by exhibiting the highest concentration of eriocitrin in comparison to other Citrus species.

Additional phenolic compounds identified by LC-MS/MS in lemon zest include: caffeoyl N-tryptophan, hydroxycinnamoyl-O-glucoside acid, vicenin 2, eriocitrin, kaempferol-3-O-rutinoside, and quercetin-3-rutinoside.

3.3 Essential Oil Constituents

The essential oil is rich in bioactive monoterpenoids such as D-limonene, β-pinene, γ-terpinene. GC-MS analysis has revealed that limonene (60.7%), β-pinene (12.6%), and γ-terpinene (10.3%) are common constituents of lemon essential oil. The essential oil extracted from the pericarp also showcases limonene, β-pinene, γ-terpinene, sabinene, myrcene, geranial (E-citral), neral (Z-citral), and linalool as key compounds. Volatile oils also include terpineol, pinene, camphene, cadinene, aldehydes such as phellandrene, geranyl and neryl acetate, citronellal, and methylheptone.

3.4 Organic Acids

The organic acid content is particularly high, ranging from 3.5 to 7.2 g per 100 g (average ~5 g per 100 g), consisting basically of citric acid with small amounts of malic, caffeic, and ferulic acid; these organic acids give lemon its very marked sour taste. The juice of the lemon is about 5–6% citric acid.

3.5 Vitamin C (Ascorbic Acid)

Vitamin C content of lemon peel is approximately 58.59 mg/100 g, while it is approximately 46.9 mg/g in the inner parts (pulp and seeds). Vitamin C levels in lemon juice range between 20 and 60 mg/100 mL of juice.

3.6 Limonoids

Limonoids found in lemon include limonin and limonin glucoside; these compounds collectively contribute to lemon's antioxidant, anti-inflammatory, and lipid-lowering effects.

3.7 Minerals and Other Micronutrients

The lemon is a good source of potassium (145 mg per 100 g of fruit), bioflavonoids, and vitamin C (40 to 50 mg per 100 g). It also contains essential vitamins and minerals including niacin, riboflavin, thiamine, choline, pantothenic acid, folate, vitamin C, vitamin B6, calcium, copper, iron, manganese, magnesium, phosphorus, potassium, and zinc.

4. Established Mechanisms of Action

4.1 Antioxidant Activity

Hesperidin's antioxidant properties are expressed mainly by direct free radical scavenging or indirectly by inhibition of prooxidative enzymes that participate in the generation of radicals, as well as by chelation of transition metals which participate in reactive oxygen species-generating reactions. The antioxidant efficacy of hesperidin is not limited only to its radical scavenging activity, but it also enhances cellular antioxidant defenses via the ERK/Nrf2 signaling pathway.

Vitamin C is a potent antioxidant that enhances immune defense, supports collagen synthesis, and mitigates oxidative damage.

4.2 Anti-inflammatory Mechanisms

Hesperidin and hesperetin are citrus flavonoids from the flavanones subclass that have anti-inflammatory, antioxidant, antitumor, and antibacterial potential. Hesperidin suppresses lipid peroxidation, nitric oxide (NO), inducible nitric oxide synthase (iNOS), and nuclear factor-kappaB (NF-κB) and boosts enzymatic and nonenzymatic antioxidant defenses in the liver; upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) mediates, at least in part, the antioxidant and anti-inflammatory potential of hesperidin.

4.3 Citrate and Urolithiasis Prevention

Citrus juices are rich in citrate — a natural inhibitor of calcium stone formation. Citrus juices provide several benefits for kidney stone prevention, including high citrate content, alkalizing effect on urinary pH, and contribution to increased fluid intake, all of which help to reduce stone formation.

4.4 Iron Absorption Enhancement

Vitamin C facilitates non-heme iron absorption by reducing ferric iron to its more absorbable ferrous form in the gut. Lemons contain small amounts of iron, but are a great source of vitamin C and citric acid, which can increase the absorption of iron from other foods.

4.5 Antimicrobial Mechanisms

The primary antimicrobial mechanisms involve citric acid and other organic acids, which lower pH and chelate metal ions, thereby inhibiting microbial growth and reducing oxidative reactions; limonene and other volatile compounds exert antimicrobial and anti-inflammatory effects by modulating various cellular signaling pathways. Minimum inhibitory concentration (MIC) values show that lemon essential oil generally exhibits acceptable antibacterial properties.

4.6 Cardiovascular-Relevant Mechanisms

Other compounds that contribute to health include narirutin, phenolic acids, and flavonols; all these compounds have antioxidant and anti-inflammatory properties, which help protect the cardiovascular system. Hesperidin, as an antioxidant, may strengthen blood vessels and prevent atherosclerosis. Diosmin, an antioxidant used in some circulatory drugs, improves muscle tone and reduces chronic inflammation in blood vessels.

5. Scientific Evidence by Area of Use

5.1 Kidney Stone Prevention (Urolithiasis / Nephrolithiasis)

This is among the most clinically investigated areas for lemon.

Thirteen articles met the criteria for inclusion in one systematic review; ten small prospective clinical studies found that orange, grapefruit, and lemon juices all increased urinary citrate levels. Only orange and grapefruit juices had an alkalinizing effect on urine pH, while lemon juice had a protective effect by raising urinary citrate levels but lacked a significant alkalinizing effect.

Of 11 patients on lemonade, 10 demonstrated increased urinary citrate levels (mean increase +383 mg per day, p <0.05); all potassium citrate therapy subjects demonstrated an increase (+482 mg per day, p <0.0001). During lemonade therapy, the stone formation rate decreased from 1.00 to 0.13 stones per patient per year (p >0.05). The authors concluded lemonade therapy appears a reasonable alternative for patients with hypocitraturia who cannot tolerate first-line therapy, but noted the need for a prospective randomized trial to validate these findings.

A literature search (PubMed, 1990–2021) failed to detect any controlled study evaluating the role of lemon juice supplementation on long-term prevention of recurrent nephrolithiasis prior to one PROBE trial; a few prior studies suggested lemon juice may reduce stone recurrence risk, but findings were limited by retrospective, observational designs and small sample sizes.

Lemon juice has consistently been found to increase urinary citrate levels without causing significant effects on urinary calcium or oxalate excretion. Lemon juice appears to have a smaller protective role than orange juice in overall urolithiasis prevention; larger and more accurate data are needed before recommendations can be made.

A randomized crossover clinical trial found that the addition of lemon-tomato juice as a source of citrate in the diet significantly decreases established risk factors for calcium oxalate stone formation in patients.

Evidence strength: Moderate for raising urinary citrate; limited and mixed for long-term stone prevention. The evidence base consists primarily of small prospective studies; large, well-controlled randomized trials remain scarce.

5.2 Cardiovascular Health

Preclinical studies and clinical trials have demonstrated therapeutic effects of hesperidin and its aglycone hesperetin in various diseases, including cardiovascular diseases. Hesperidin and hesperetin safeguard cardiovascular health by exhibiting anti-inflammatory and antioxidant properties, as well as other pharmacological effects.

Hesperidin is a bioactive plant compound mainly found in citrus fruits, including lemons, clementines, grapefruit, and mandarins. Supplementation with hesperidin has various benefits, including anti-inflammatory, anticancer, and antioxidant characteristics; many animal and human studies have explored hesperidin's cardiovascular preventive benefits, and RCTs have investigated the effectiveness of hesperidin consumption on various cardiovascular disease risk factors.

Intake of fruits high in vitamin C is linked to reduced heart disease risk; low levels of vitamin C in the blood are also associated with increased risk of stroke, especially among those who are overweight or have high blood pressure. Intake of isolated fibers from citrus fruits has been shown to decrease blood cholesterol levels, and the essential oils in lemons can protect LDL cholesterol particles from becoming oxidized.

A study in rodents reported prolonged bleeding and thrombin time with C. limon, suggesting a cardioprotective role in preventing thrombosis. This finding is preclinical only.

Evidence strength: Preliminary to moderate. Epidemiological data associating citrus consumption with reduced cardiovascular risk are available, but human trials with lemon specifically (rather than isolated hesperidin or citrus in general) are limited. Most mechanistic evidence derives from in vitro and animal models.

5.3 Scurvy and Vitamin C Deficiency

British naval physician Lind documented that there was some substance in citrus fruits that could cure scurvy; he developed a method to concentrate and preserve citrus juice for use by sailors, and the British Navy was given a daily ration of lime or lemon juice to overcome ascorbic acid deficiency. The antiscorbutic effect of lemon is historically one of the best-documented medicinal uses and is now firmly established as being attributable to ascorbic acid (vitamin C).

Evidence strength: Well established historically and biochemically. The causal mechanism (vitamin C deficiency) and the remedy (citrus juice providing ascorbic acid) are not in question.

5.4 Antimicrobial Activity

Recently scientifically proven therapeutic activities of C. limon include anti-inflammatory, antimicrobial, anticancer, and antiparasitic activities. These recently scientifically proven therapeutic activities include anti-inflammatory, antimicrobial, anticancer, and antiparasitic activities.

In vitro and in situ studies with lemon essential oil have demonstrated bactericidal and bacteriostatic activity against a range of pathogens. GC-MS analysis revealed limonene (60.7%), β-pinene (12.6%), and γ-terpinene (10.3%) as common constituents of lemon essential oil, and MIC values showed that the oil generally exhibits acceptable antibacterial properties.

Evidence strength: Preliminary. Most antimicrobial evidence is in vitro or in food-preservation contexts. Clinical human trial evidence specifically for infection treatment with lemon is lacking.

5.5 Cancer-Related Evidence

A meta-analysis of epidemiological studies associates the consumption of citrus fruit with a larger protective effect against oral cancer (odds ratio, 0.38; 95% CI, 0.26 to 0.56) than overall fruit consumption.

Previous studies have confirmed the anticancer potential of citrus peels with potent activity reported for lemon peel; daily consumption of citrus fruits is connected with a diminished risk for gastric cancer. Ethyl acetate and petroleum ether extracts of citrus lemon have anticancer activity against various human cancer cell lines. These findings remain primarily in vitro.

Research shows that limonin has broad and effective anticancer activity; limonin has certain cytotoxicity to human colon cancer (Caco-2) cells and can reduce the transcription rate of BCL2/Bax and induce the release of cytochrome C by activating the endogenous apoptotic pathway. Again, these findings are from cell-based studies.

A number of clinical and epidemiological studies on anti-carcinogenic effects of ascorbic acid in humans did not show any conclusive beneficial effects on various types of cancer except gastric cancer; more mechanistic and human in vivo studies are needed.

Evidence strength: Preliminary. Epidemiological associations exist for certain cancer types, particularly oral and gastric cancers in the context of overall citrus consumption. Direct interventional human trials with lemon as a cancer treatment are lacking. In vitro data are substantial but not translatable without further clinical investigation.

5.6 Glycemic Metabolism and Diabetes

Beneficial effects of lemon leaf and peel extracts on glucose metabolism in diabetic rat models have been reported. In vitro assays pointed to strong alpha-amylase inhibition. In a tumor necrosis factor alpha–induced insulin resistance model in vitro, lemon extract restored adipocyte insulin sensitivity and function via increased proliferator-activated receptor gamma gene expression.

Emerging studies suggest that regular consumption of lemon juice or peel extract can aid in weight management, improve lipid profiles, and protect against oxidative stress–related diseases.

Evidence strength: Very preliminary. Available data are predominantly in vitro and animal-based; well-powered human clinical trials are lacking.

5.7 Iron Absorption and Anemia Prevention

Because lemons can enhance the absorption of iron from foods via vitamin C and citric acid, they may help prevent anemia. Vitamin C's role in non-heme iron absorption is a well-characterized mechanism at the biochemical level, established across many citrus and non-citrus studies.

Evidence strength: Moderate for the mechanism of vitamin C–enhanced iron absorption, which is well established in nutritional science. Specific human trials with lemon on anemia endpoints are limited.

5.8 Neuroprotection (Preclinical)

Hesperetin, a flavanone class of citrus flavonoid, is a derivative of hesperidin found in citrus fruits including lemons; it has been extensively reported that hesperetin exerts neuroprotective effects in experimental models of neurodegenerative diseases. More and more studies have begun to pay attention to the therapeutic prospect of hesperidin in central nervous system (CNS) diseases, particularly stroke.

Evidence strength: Preclinical only. Human clinical trials specifically using lemon-derived hesperidin for neurological conditions are not yet established.

6. Body Systems and Health Areas of Association

• Urological/renal system: Prevention of hypocitraturic calcium oxalate kidney stones via citrate provision
• Cardiovascular system: Antioxidant and anti-inflammatory effects of hesperidin, diosmin, and vitamin C; potential modulation of lipid profiles
• Immune system: Vitamin C enhances immune defense, supports collagen synthesis, and mitigates oxidative damage.
• Gastrointestinal system: Used in traditional medicine to treat conditions including irregular digestion. Citrus juice is often implicated in the worsening of gastroesophageal reflux disease symptoms.
• Hematological system: Enhancement of non-heme iron absorption; potential anticoagulant effects (preclinical)
• Dermatological system: Phototoxic furanocoumarins relevant to topical exposure (see Safety); in vitro use for skin conditions in traditional Xhosa medicine
• Endocrine/metabolic system: Preliminary evidence for alpha-amylase inhibition, insulin sensitization (in vitro and animal models)
• Musculoskeletal/connective tissue: Collagen synthesis support via vitamin C
• Oncological (investigational): Epidemiological associations with reduced oral and gastric cancer risk; in vitro anticancer activity of limonoids and flavonoids

7. Dosage Forms and Dosages Reported in Studies

The following dosages appear in the peer-reviewed or authoritative literature cited and are reported descriptively, as they appear in those sources.

• Nephrolithiasis (lemonade therapy): 120 mL of concentrated lemon juice (containing 5.9 g of citric acid) diluted in 2 L of water daily (mean treatment duration 44.4 months) was used in a small study evaluating urinary metabolic parameters and stone formation in patients with hypocitraturic calcium nephrolithiasis.
• Nephrolithiasis (lemon juice RCT): In the PROBE trial, patients completing 24 months of follow-up were assigned to a standard diet with lemon juice supplementation group or a control group.
• Purified D-limonene (cancer research): D-limonene, the primary bioactive monoterpene in lemon essential oil, has been studied at doses ranging from 0.5–12 grams daily in clinical trials; however, these studies evaluated purified d-limonene supplements, not whole lemon preparations.
• Lemon peel (herbal reference): 0.25–5 g of the peel per day taken in capsule form or drunk as a tea is cited in herbal practice references.
• Clinical dosing note: Small clinical trials have suggested potential roles in hypocitraturic calcium nephrolithiasis, aromatherapy, and reducing glycemic response, but clinical data are lacking to provide dosing recommendations.

8. Safety Considerations and Interactions

8.1 General Safety Status

Contraindications have not been identified. Lemon has generally recognized as safe (GRAS) status when used as food. Lemon rind and fruit are safe to use during pregnancy and breastfeeding taken in normal amounts as used in culinary recipes.

8.2 Dental Erosion

Severe erosion of the enamel, dentinal hypersensitivity, and excessive pigmentation of eroded areas have been documented in a clinical case report, with lesions on the enamel caused by the patient having taken lemon juice for approximately one year during main meals and as a snack. In vitro analysis clearly demonstrated the harmful effect of canned lemon juice on deciduous enamel; stereomicroscopy showed loss of gloss and alteration in normal color, with irregular loss of dental tissue that became more serious as the time of incubation increased.

8.3 Phototoxicity and Phytophotodermatitis

Bergapten (aka 5-methoxypsoralen or 5-MOP) is a naturally occurring, phototoxic furanocoumarin in Citrus fruits. Phytophotodermatitis is a phototoxic cutaneous eruption due to skin exposure to furocoumarins, which are organic chemical compounds produced by a variety of plants, and ultraviolet radiation from sunlight. Phytophotodermatitis was observed in rats following exposure to undiluted lemon fruit juice, and was noted in numerous patients exposed to the juices of lemons and limes.

An additional risk of skin cancer arising from the intake of typical quantities of furocoumarin-containing foods, which leads to an exposure well below the phototoxic dose range, was regarded as negligible by the German DFG/SKLM. For phototoxic effects, the SKLM did not see a significant risk associated with the consumption of typical quantities of correctly stored, processed foods that may contain furocoumarins. The phototoxic risk applies primarily to direct topical exposure of skin to lemon juice followed by UV exposure.

8.4 Gastrointestinal Effects

Citrus juice is often implicated in the worsening of gastroesophageal reflux disease symptoms. The high citric acid content of lemon juice is the most probable mechanism.

8.5 Potential Drug Interactions

A study in rodents reported prolonged bleeding and thrombin time with C. limon, suggesting potential interaction with anticoagulant medications. Citrus limon juice has demonstrated anticoagulant effects in animal studies, significantly prolonging bleeding time and thrombin time, which could interact with anticoagulant medications. These findings are currently preclinical; clinical evidence confirming this interaction in humans with lemon specifically is not yet established.

Attention should be paid to the safety of use and potential phototoxicity of lemon raw materials.

8.6 Allergic Contact Dermatitis

Case reports describe allergic contact dermatitis reactions to citrus-derived ingredients. Lemon is included among citrus fruits that may cause protein contact dermatitis, particularly in occupational settings involving repeated skin exposure.

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