salvia

Sage (Salvia officinalis L.): A Comprehensive Reference

1. Identity and Botanical Description

Taxonomy and Nomenclature

Salvia officinalis (sage) is a plant in the family Labiatae/Lamiaceae. It is a perennial, evergreen subshrub with woody stems, grayish leaves, and blue to purplish flowers. The genus name carries deep linguistic roots: the name Salvia is derived from the Latin salvere, meaning "to save," in reference to the medicinal properties of the plant. The epithet officinalis derives from the Latin word officina, which was the traditional storeroom of a monastery where herbs and medicines were stored. In common usage, the plant is known by numerous names: Salvia officinalis has numerous common names including sage, common sage, garden sage, golden sage, true sage, culinary sage, kitchen sage, Dalmatian sage, and broadleaf sage.

Among all Salvia species, S. officinalis L., known as common or Dalmatian sage, is one of the most prominent and widely cultivated for its varied applications. On a global scale, over 100 Salvia species have been documented for their ethnobotanical significance, making the genus one of the most frequently cited for traditional uses, including culinary, medicinal, and ritual contexts. Within the broader genus, closely related species used medicinally include S. rosmarinus (rosemary), S. officinalis subsp. lavandulifolia (Spanish sage), and S. fruticosa (Greek sage), largely known for their therapeutic effects owing to their bioactive constituents.

Geographic Origin and Cultivation

Salvia officinalis is native to the Middle East and Mediterranean areas, but today has been naturalized throughout the world. More precisely, its native distribution spans Albania, Bosnia and Herzegovina, Croatia, France, Germany, Greece, Italy, Montenegro, North Macedonia, Serbia, Slovenia, Spain, and Switzerland. S. officinalis is commercially cultivated for its essential oil and is grown throughout Europe and the United States, and in parts of Turkey, Yugoslavia, and Canada.

Morphology and Plant Part Used

Sage is a medium-sized perennial shrub that can reach up to 2 feet in height, with erect stems, hairy green branches, simple elongated light green/silver colored leaves, and long blue/purple flowers. The Old World type grows to approximately 60 cm tall and wide, with lavender flowers most common, though they can also be white, pink, or purple; the plant flowers in late spring or summer, and the leaves are oblong, ranging in size up to 65 mm long by 25 mm wide. The primary medicinal and culinary plant part is the leaf. Sage leaf, as defined by the European Pharmacopoeia, consists of the whole or cut dried leaves of Salvia officinalis L., containing not less than 12 ml/kg of essential oil for the whole drug and minimum 10 ml/kg for the cut drug, both calculated with reference to the anhydrous drug.

Common Preparations and Dosage Forms

Sage is available in multiple forms for medicinal and culinary use. According to a 2016 EMA herbal monograph of Salvia officinalis, the plant is consumed orally as a dry/liquid extract or tincture for the treatment of heartburn, bloating, excessive sweating, and relief of inflammation of the mouth or throat; an aqueous infusion of Salvia officinalis is also applied to the skin in traditional medicine for the relief of minor inflammation. The EMA monograph recognizes the following herbal preparations: comminuted herbal substance, liquid extract (1:1) in ethanol 70% V/V, dry extract (4–7:1) with extraction solvent water, liquid extract (1:3.5–5) in ethanol 31.5% V/V, and liquid extract (1:4–5) in ethanol 50% V/V. Sage tincture is produced from 1 part of comminuted sage leaf and 10 parts of ethanol (70% V/V) and is a separate monograph in the European Pharmacopoeia. Leaves are highly aromatic and are used for extraction of essential oil, which contains more than 49 aromatic components. Additional preparations encountered in clinical research include standardized ethanolic leaf extracts, capsules of dried leaf powder, aromatherapy with the essential oil, and topical gels.

2. Traditional and Historical Use

Ancient Greek and Roman Traditions

The fame of sage as a healing herb goes back to Greek antiquity, but it may be that the virtues of Salvia fruticosa were conflated with those of Salvia officinalis in the European Middle Ages. Sage was known to Theophrastus and other ancient authors such as Dioscorides as elelisphakon, although the latter gives a number of other names, including salvia. The genus name itself reflects Roman reverence for the plant: although the genus was recognized by both Egyptian and the Greek civilizations, the name Salvia is derived from the Latin word salvēre, meaning "to feel healthy, to heal," given by the Roman Empire.

Medieval European Use

Sage was used during the Middle Ages to treat many maladies including fevers, liver disease, and epilepsy. The herb was used in England to make a tea that was considered a pleasant and healthful beverage. The sixteenth-century English herbalist John Gerard was familiar with both S. officinalis and S. fruticosa, but considered the latter to be of greater medicinal value. The word "sage" itself passed into English via these classical traditions: the genus name Salvia comes from the Latin salvus — healthy, safe, saved — meaning "the healing," from which the English word "sage" derives; the epithet officinalis further identifies it as an ancient medicinal plant, since "officina" was the sales room of a pharmacy.

Mediterranean and Middle Eastern Folk Medicine

In folk medicine, S. officinalis has been used for the treatment of different kinds of disorders including seizure, ulcers, gout, rheumatism, inflammation, dizziness, tremor, paralysis, diarrhea, and hyperglycemia. Salvia officinalis can be considered a relevant example of a plant with evidence-based use in traditional medicine as well as modern phytotherapy; it is officially recognized as a medicinal plant, with the leaves being used not only to prepare extracts for the treatment of skin disorders, minor wounds, mouth and throat disorders, but also in the treatment of gastrointestinal disorders in the form of comminuted herb or aqueous and hydro-alcoholic extracts for oral use.

For a long time, sage species have been used in traditional medicine for the relief of pain, protecting the body against oxidative stress, free radical damage, angiogenesis, inflammation, bacterial and virus infection. In traditional medicine, it is used as a supportive agent for ailments and inflammations of the throat, mouth, and teeth, and as an expectorant for bronchial diseases. Traditionally, sage was used for digestive, respiratory, and skin problems and other health conditions.

Global Traditional Context

Among the most widely known and traditionally used species in the Old World are Salvia officinalis from the Mediterranean, and Salvia miltiorrhiza from China. Traditionally, garden sage has been used for the treatment of a multitude of ailments such as localized pain, rheumatism, convulsion, arthritis, vertigo, diarrhea, sclerosis, respiratory, metabolic, and mental disorders. In Valencia, Spain, some wild and cultivated sages are used for medicinal purposes, with Salvia officinalis subsp. lavandulifolia widely employed and known for the production of Spanish sage oil and herbal products.

3. Key Constituents and Active Compounds

Essential Oil Components

Principal components of the essential oil, in addition to thujone, are 1,8-cineole and camphor. The principal components in the sage oil are 1,8-cineole, camphor, α-thujone, β-thujone, α-humulene, rosmarinic acid, and quercetin. These constituents include compounds such as 1,8-cineole (eucalyptol), α-thujone, camphor, and camphene found in the essential oil, as well as phenolic compounds such as caffeic acid, rosmarinic acid, and salvianolic acid. Camphor content in commercial sage sources is notably variable: according to the EMA monograph, the principal components of Salvia officinalis oil are thujone, 1,8-cineole, and camphor; in 25 different commercial sources of sage leaves, camphor levels varied from 7–50%.

Phenolic Acids and Hydroxycinnamic Derivatives

Hydroxycinnamic acid derivatives constitute up to 3.5% of the plant, including the caffeic acid dimer rosmarinic acid, caffeic acid trimers (melitric acid A, methyl melitrate A, sagecoumarin, and salvianol acid K), and a tetramer (sagerinic acid). Salvianolic acid, which is a rosmarinic acid dimer isolated from the sage extract, showed high antioxidant activity and is a significant scavenger of free radicals. The antioxidant properties of sage have been studied intensively and are found to be related to the presence of rosmarinic acid and carnosic acid.

Phenolic Diterpenes

Carnosic acid is a labdane-type diterpene present in plant species of the Lamiaceae family, such as rosemary (Rosmarinus officinalis) and common salvia (Salvia officinalis). This lipid-soluble compound is recognized for its high antioxidative capacities, which have led to many industrial applications in the fields of foods and beverages, personal care, nutrition, and health. Carnosic acid (salvin) possesses antioxidative and antimicrobial properties and is increasingly exploited within the food, nutritional health, and cosmetics industries.

Triterpenes

Triterpenes constitute up to 3.5% of the plant, predominantly as pentacyclic triterpene acids — mainly ursolic acid (up to 3.5%) and oleanolic acid (up to 0.4%) — and triterpene alcohols α- and β-amyrin; flavonoids represent approximately 1.1%, principally as flavones and their glycosides including luteolin, 6-hydroxyluteolin, 6-methoxyluteolin, and apigenin. Phytochemical analysis has confirmed that the quantitatively dominant compounds in sage extract, as quantified by HPLC and NMR methods, are ursolic acid followed by oleanolic acid. In addition to the essential oil components, the leaves contain tannins, diterpene bitter principles, triterpenes, steroids, flavones, and flavonoid glycosides.

Other Constituents

Salvia officinalis is an important medicinal and aromatic plant because of its bioactive components, which include phenolics, terpenoids, polyphenols, and flavonoids. Phenolic compounds such as carnosol, carnosic and rosmarinic acids, rosmadial, rosmanol, epirosmanol, methyl carnosate, and luteolin-7-O-β-glucopyranoside have high antioxidative activity and are usually extracted from sage with ethanol. In terms of flavonoids, 6-hydroxyflavones are characteristic of Salvia species and can be used as chemosystematic markers.

4. Mechanisms of Action

Antioxidant Activity

Phenolic compounds can either stimulate endogenous antioxidant defense systems or scavenge reactive species. The antioxidant properties of S. officinalis are attributed to its flavonoids and phenolic acids. Due to its content of carnosic acid, carnosol, and rosmarinic acid, sage has antioxidant, anti-inflammatory, anticancer, antidiabetic, neuroprotective, antiaging, antimicrobial, and antiviral properties.

Anti-Inflammatory Pathways

Numerous biochemical pathways contribute to sage's anti-inflammatory actions, but cytokine modulation and NF-κB suppression are key players. By inhibiting IκBα's phosphorylation and degradation, carnosic acid and rosmarinic acid stop the NF-κB transcription factor from moving into the nucleus, which inhibits the production of chemokines (like MCP-1) and TNF-α, IL-6, and IL-1β. Carnosol, carnosic acid, ursolic acid, oleanolic acid, and rosmarinic acid have been identified as key compounds in sage extracts with anti-inflammatory and anticarcinogenic properties; because PGE2 formation through the inducible PGE2 synthase mPGES-1 plays a critical role in the progression of both inflammation and cancer, sage extracts have been investigated for mPGES-1 inhibition.

Cholinesterase Inhibition (Cognitive Mechanism)

The anticholinesterase activity of several Salvia species and their constituents has been investigated in the search for new drugs for the treatment of Alzheimer's disease; the inhibition of acetylcholinesterase in vitro by an ethanolic extract of S. officinalis (at 2.5 mg/ml) was 68%, and by oils of S. officinalis and S. lavandulaefolia (at 0.1 µg/ml) was 52% and 63%, respectively. The monoterpenes 1,8-cineole and α-pinene from the oil have been identified as the inhibitors. In one study, the essential oil was found to be a potent inhibitor of human acetylcholinesterase (AChE) and consisted almost exclusively of monoterpenoids.

Hypoglycemic and Metabolic Pathways

S. officinalis's hypolipidemic and hypoglycemic effects are linked to peroxisome proliferator-activated receptor-gamma (PPARγ) activation, a nuclear receptor protein that regulates glucose and lipid metabolism and may be used to treat metabolic disorders. S. officinalis also increases GLUT4, which regulates glucose homeostasis. Rosmarinic acid, caffeic acid, and salvianolic acid B showed the most promising interactions with PTGS2, DPP4, AMY1A, PTB1B, PPARG, GSK3B, and RELA in network pharmacology analyses of antidiabetic mechanisms.

Antimicrobial Activity

The essential oil of sage has shown inhibitory activity against Gram-positive bacteria (Bacillus subtilis) and Gram-negative bacteria (Escherichia coli, Shigella sonnei, Salmonella species, Klebsiella ozanae), as well as against fungi including Candida albicans, C. krusei, C. pseudotropicalis, Torulopsis glabrata, and Cryptococcus neoformans. Sage oil's antimicrobial properties have been attributed principally to the presence of α- and β-thujone. Both in vitro and in vivo studies demonstrate its effectiveness against bacterial infections.

5. Scientific Evidence by Area of Health Use

5.1 Cognitive Function, Memory, and Alzheimer's Disease

This is among the most rigorously investigated areas for sage, with multiple human clinical trials published.

Healthy adults — acute cognition and mood: One double-blind, placebo-controlled, balanced crossover study assessed the effects of a single dose of a S. lavandulaefolia essential oil on cognitive performance and mood; 36 healthy participants received capsules containing either 50 µL of the essential oil or placebo on separate occasions, 7 days apart, and cognitive function was assessed using computerized memory and attention tasks and the Cognitive Demand Battery before treatment and 1 and 4 hours post-dose. The results confirmed previous observations of the inhibitory properties of S. officinalis on cholinesterase and improved mood and cognitive performance after a single dose in healthy young participants.

Dose-response effects in healthy volunteers: Authors reported that a 333 mg dose of sage was associated with significant enhancement of secondary memory performance at all testing times; placebo exhibited the characteristic performance decline over the day, and although to a lesser extent, similar effects were observed with other doses. Both doses of S. officinalis leaves preparation led to post-dose improved ratings of mood in the absence of stress; the lower dose reduced anxiety while the higher dose increased alertness, calmness, and contentedness on the Bond–Lader scales. The clinical studies involving sage and cognition typically found doses between 300 and 600 mg to be most effective for memory enhancement.

Healthy older volunteers: Clinical research conducted on healthy older adults showed that taking a single 333 mg dose of common sage extract improved attention accuracy compared with placebo. Secondary memory scores in the extract group were positively influenced in terms of single task, normal and delayed word recognition, immediate word recall, accuracy of attention, and working memory tasks; there was no significant improvement in the speed of memory and attention, but the authors stated that the standardized S. officinalis extract exerted a significant acute enhancement in memory, especially influencing secondary memory factors. However, the limited number of human subjects in the study and the lack of clarity on the basis of standardization are acknowledged weaknesses of this clinical trial.

Mild-to-moderate Alzheimer's disease: In a double-blind, randomized controlled trial, 39 patients with mild-to-moderate Alzheimer's disease were given 60 drops of sage extract essential oil or placebo each day over the course of 4 months. At 4 months, Salvia extract produced a significantly better outcome on cognitive function and CDR total score than placebo (ADAS-cog: d.f.: 1, F = 4.77, P = 0.037; CDR: d.f.: 1, F = 10.84, P < 0.05). The study can be criticized for its small number of human subjects and its use of a non-standardized extract.

Overall evidence strength: There are many preclinical studies and excellent reviews referring to the favorable effect of different species of sage against cognitive dysfunction related to Alzheimer's disease; current reviews discuss clinical studies that provide evidence for the effect of Salvia species on cognitive dysfunction. As of 2017, S. officinalis was under preliminary research for its possible effects on cognitive performance in both healthy individuals and those with cognitive decline, although its long-term effects remain undetermined. Only small amounts of research have been done on the use of sage for health conditions, so definitive conclusions about its effects cannot be reached. The body of evidence is promising but limited by small sample sizes, lack of standardization, and the predominance of acute rather than long-term interventions.

5.2 Menopausal Symptoms (Vasomotor and Other)

Today, sage is promoted as a dietary supplement for managing menopause symptoms, enhancing memory, and reducing cholesterol levels.

Key clinical trial evidence: The first placebo-controlled, confirmatory clinical trial demonstrated efficacy for a Salvia officinalis preparation shown not only in reduction of hot flashes but of other climacteric symptoms as well; the preparation improved not only vasomotor symptoms (measured by MRS and HFS scores) but simultaneously exerted a positive impact on accompanying somato-vegetative and psychological symptoms, thus addressing a broad range of menopausal complaints. This double-blind randomized clinical trial was performed on 100 postmenopausal women with hot flashes. The study women were divided into two groups daily treated with 3 salvia or placebo tablets (100 mg) for 8 weeks.

Sleep improvements: Study findings showed that the average post-intervention sleep score in common sage groups decreased by 3.8 units when compared with pre-intervention, and this decline was statistically significant; in the control group, after treatment, the sleep score average remained the same.

Evidence strength: The clinical evidence for sage in menopausal hot flashes is more developed than in some other areas, supported by at least one double-blind, placebo-controlled confirmatory trial. However, total study numbers remain limited and sample sizes small. Salvia officinalis has been described as a valid option for women reluctant or contraindicated to hormone replacement therapy (HRT) who seek a natural alternative treatment of their vasomotor and other typical menopausal symptoms. These results remain preliminary and cannot yet be considered definitive.

5.3 Blood Glucose and Diabetes

Human clinical trial: A double-blind clinical trial was carried out on 80 type II diabetic patients who had not reached ideal control of the disease; patients were randomly divided into two equal groups, with the case group receiving Salvia officinalis and the control group receiving placebo tablets three times a day for three months. The 2-hour postprandial (2hpp) blood sugar and cholesterol levels were significantly decreased in Salvia officinalis-treated patients compared to the control group (p < 0.05); there were no significant changes in glycosylated hemoglobin (HbA1c) and fasting blood sugar (FBS) between the two groups. Salvia officinalis might be beneficial in diabetic patients to reduce 2hpp glucose and cholesterol; however, higher doses might be needed to decrease fasting blood glucose and glycosylated hemoglobin.

Animal and mechanistic data: The antidiabetic effect of sage ethanolic extract was examined in normal and streptozotocin-induced diabetic rats; oral administration of sage extract at 0.1, 0.2, and 0.4 g/kg body weight and glibenclamide (600 µg/kg) for 14 days was evaluated. Oral administration of 0.2 and 0.4 g/kg body weight of the sage extract for 14 days exhibited a significant reduction in serum glucose, triglycerides, total cholesterol, urea, uric acid, creatinine, AST, and ALT, and increased plasma insulin in streptozotocin-induced diabetic rats.

Evidence strength: Evidence in humans is limited to a small number of trials with modest sample sizes. Animal and mechanistic data are more extensive but cannot be directly extrapolated to humans. The effect on postprandial glucose in one human trial was statistically significant; effects on HbA1c and fasting glucose were not demonstrated at the doses studied.

5.4 Oral Health and Throat Inflammation

Drinking or gargling sage leaf infusions have been thought to soothe a sore throat or gums, and these effects have been ascribed to volatile compounds such as 1,8-cineole, borneol, camphor, and thujones. The leaves are used to prepare extracts for the treatment of skin disorders, minor wounds, and mouth and throat disorders.

Periodontitis clinical trial: Given the adverse effects of standard adjunctive therapies, Salvia officinalis presents a promising herbal alternative due to its anti-inflammatory and antimicrobial properties; one study assessed the local application of Salvia officinalis gel as an adjunct to scaling and root surface debridement (RSD) to manage periodontitis, conducted as a randomized, controlled split-mouth clinical trial involving 14 systemically healthy periodontitis patients. The EMA monograph recognizes the traditional use of sage leaf preparations for mouth and throat inflammation. The mechanisms by which clinical effects of sage leaf are achieved are not yet fully understood, and sage oil's antimicrobial properties have been attributed principally to the presence of α- and β-thujone.

Evidence strength: The use of sage for oral/throat applications has long traditional backing and limited but supportive clinical data, particularly as an adjunct in periodontal care. The European Medicines Agency includes this traditional use in its monograph, but formal large randomized trials are lacking.

5.5 Antioxidant Effects

DPPH, FRAP, and ABTS tests demonstrated that the best antioxidant activity of S. officinalis essential oils was observed in the full flowering stage, with IC50 values of 0.011 ± 3.29, 0.012 ± 2.17, and 0.014 ± 1.81 mg/mL for the DPPH, FRAP, and ABTS assays, respectively. The antioxidant properties of S. officinalis are primarily due to its flavonoids and phenolic acids. Recent research also suggests that S. officinalis has the potential to extend the shelf life of various foods by reducing lipid oxidation, making it an important ingredient in the food industry as a natural food additive.

Evidence strength: Antioxidant activity is well-characterized in vitro and has been demonstrated in preclinical and in vivo models. Translation of antioxidant activity into specific clinical health outcomes in humans has not been systematically established.

5.6 Antimicrobial Properties

Pharmacological findings reported for S. officinalis include anticancer, anti-inflammatory, antinociceptive, antioxidant, antimicrobial, antimutagenic, antidementia, hypoglycemic, and hypolipidemic effects. The essential oil has shown inhibitory activity against both Gram-positive and Gram-negative bacteria, as well as multiple fungal species including Candida albicans, Cryptococcus neoformans, and others. The vast majority of antimicrobial data comes from in vitro studies; the clinical relevance of these findings in humans has not been established through rigorous trials.

5.7 Lipid Profile and Cardiovascular Markers

Bioactive substances such as ursolic acid, carnosic acid, flavonoids, and rosmarinic acid work in concert to provide sage its anti-inflammatory and cardioprotective properties; these chemicals target molecular pathways linked to oxidative stress, inflammation, and vascular dysfunction. In the human clinical trial on diabetic patients described in section 5.3, cholesterol levels were significantly decreased in Salvia officinalis-treated patients compared to the control group (p < 0.05). Evidence for lipid-lowering effects in humans is limited to studies of modest design and size.

6. Body Systems and Health Areas Associated with Sage

• Nervous system / Cognition: Cholinesterase inhibition, modulation of mood, secondary memory improvement, and potential relevance to Alzheimer's disease have been studied in human trials.
• Endocrine / Reproductive: Vasomotor symptom reduction (hot flashes, night sweats) in menopausal women investigated in double-blind trials; traditional use as an emmenagogue.
• Metabolic / Endocrine (glucose regulation): Reduction in postprandial blood glucose and cholesterol in a human trial in type 2 diabetic patients; PPARγ activation proposed as mechanism.
• Oral / Oropharyngeal: Anti-inflammatory and antimicrobial effects applied to sore throat, gum disease, and periodontal care; recognized in the EMA monograph.
• Gastrointestinal: Traditional use for heartburn, bloating, and digestive dysfunction; included in EMA monograph indications.
• Integumentary / Dermatological: Topical application for minor wounds, skin inflammation; traditional use recognized by EMA.
• Cardiovascular: Preclinical and mechanistic data on cardioprotective effects via antioxidant and anti-inflammatory pathways; limited human evidence.
• Immune / Anti-infective: Broad-spectrum in vitro antimicrobial and antifungal activity; clinical application not yet established.

7. Dosage Forms and Doses Reported in Studies

Dosages vary widely depending on the preparation, indication, and study. The following are derived from official monographs and published clinical research:

• Dried leaf (infusion/tea): Sage leaves: 4 to 6 g daily dose; sage tincture: 2.5 to 7.5 g daily dose; fluid extract: 1.5 to 3 g daily dose; sage oil (external): 0.1 to 0.3 g daily dose.
• Dry extract and tincture (EMA/ESCOP/monograph range): Non-standardized ethanolic extracts (dry extract, tincture): 0.3–2.25 grams dry leaf equivalent per day, per EMA 2016, Mills and Bone 2005, and ESCOP 2003.
• Marketed products (Europe): The EMA 2016 herbal monograph describes Salvia officinalis being consumed orally as a dry/liquid extract or tincture; most medicinal uses in Europe are marketed at a daily dose of 1.5–2.5 g/d; in Spain, a dry extract is marketed for excessive sweating at a dose of 360 mg/d, equivalent to 500–800 mg of dried Salvia officinalis leaves.
• Clinical trials — cognition (acute, healthy adults): A 333 mg dose of sage was associated with significant enhancement of secondary memory performance in human trials. A dose of 50 µL of essential oil in capsule form was administered to 36 healthy participants in a crossover study.
• Clinical trial — Alzheimer's disease: Patients received 60 drops of sage extract essential oil daily over 4 months.
• Clinical trial — diabetes: The case group received Salvia officinalis and the control group received placebo tablets three times a day for three months.
• Clinical trial — menopause: Women were daily treated with 3 salvia or placebo tablets (100 mg each) for 8 weeks.
• Oral gargle for throat inflammation: For gargles and rinses: 2.5 g of the drug several times daily.

8. Safety Considerations and Drug Interactions

General Safety Status

S. officinalis is classified as Generally Recognized as Safe (GRAS) for use in food by the U.S. Food and Drug Administration (FDA); however, this classification does not apply to high-dose or medical applications. Sage is likely safe in the amounts commonly found in foods, and larger amounts have been used safely for up to 8 weeks in research studies. However, some species of sage, including common sage (S. officinalis), contain a component called thujone that can be toxic if consumed in large amounts; therefore, sage may be unsafe in high doses or if consumed for long periods of time.

Thujone Toxicity

The essential oil of Salvia officinalis contains constituents like thujone and camphor, which have toxic effects in high doses; toxicological dose limits have been set based on available data, and the toxic effect appears to be of central nervous origin with convulsions as the main symptom; based on existing data, it can be concluded that because of the toxic properties of the essential oil, one should not exceed recommendations concerning the posology of sage leaf. Some species of sage, including common sage (S. officinalis), contain a constituent called thujone that has caused seizures in animal models, and cases of seizures associated with consumption of sage essential oil (which is high in thujone) have been reported in people. Rats given higher dosages of thujone (25 or 50 mg/kg for 13 weeks) experienced seizures. Too much thujone can cause seizures and damage the liver and nervous system; the amount of thujone varies with the species of sage, the time of harvest, growing conditions, and other factors.

Pregnancy and Lactation

It may be unsafe to use sage during pregnancy because its component thujone may have harmful effects. Pure Salvia officinalis oil and extract consumption is contraindicated during pregnancy, due to its abortifacient and emmenagogic properties. Little is known about whether it's safe to use sage while breastfeeding.

Hormone-Sensitive Conditions

Spanish sage (Salvia lavandulaefolia) might have the same effects as estrogen; if an individual has any condition that might be made worse by estrogen (such as breast cancer, uterine cancer, ovarian cancer, endometriosis, or uterine fibroids), use of Spanish sage should be avoided.

Duration of Use

The EMA monograph specifies that sage preparations for certain uses should not be used for more than 2 weeks for specific topical or throat applications. High-dose or long-term use of sage may not be safe.

Drug Interactions

Potential interactions reported include: sage may decrease effects of acetazolamide by pharmacodynamic antagonism; this is a minor interaction of unknown significance based on the theoretical possibility that some species of sage may cause convulsions. Due to sage's cholinesterase-inhibiting properties, interactions with cholinergic or anticholinergic medications are theoretically plausible and warrant attention. Because of potential estrogenic activity (particularly with S. lavandulaefolia), concurrent use with estrogen-modulating drugs or hormonal therapies should be considered carefully.

Known Contradictions

The EMA herbal monograph for Salvia officinalis folium lists hypersensitivity to the active substance(s) as a contraindication. For further information on thujone-related safety, the EMA's public statement on the use of herbal medicinal products containing thujone (EMA/HMPC/732886/2010) should be consulted; a European Union list entry is not supported due to lack of adequate genotoxicity data.

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