Comparison of Spanish Sage (Salvia lavandulifolia), Clary Sage (Salvia sclarea), and Dalmatian Sage (Salvia officinalis)

Spanish Sage (Salvia lavandulifolia), Clary Sage (Salvia sclarea) and Dalmatian Sage (Salvia officinalis) - botanical differences, chemical composition of essential oils, therapeutic use, safety and toxicity.

Botanical and morphological differences

1. Common Sage (Salvia officinalis) - A perennial subshrub reaching approximately 60 cm in height and a similar width. It has woody stems at the base and elliptical, thickened, gray-green leaves, up to ~6.5 cm long, covered with dense hairs on the underside. It blooms in late spring and summer, producing spike-shaped inflorescences with numerous purple (rarely white or pink) flowers.

2. Spanish Sage (Salvia lavandulifolia) - A small, compact subshrub closely related to common sage, reaching ~30 cm in height and width. It has ascending stems with narrow, lanceolate, gray-green leaves <5 cm long, arranged oppositely. When crushed, the leaves exude a rosemary-like aroma. It blooms in late spring, developing short inflorescences with sparse, pale lavender flowers.

3. Nutmeg Sage (Salvia sclarea) - A biennial (rarely a short-lived perennial) herbaceous plant of impressive size. In the first year, it forms a ground-level rosette of large, ovate leaves up to ~20 cm long, covered with soft hairs. In the second year, a branched inflorescence grows, 1-1.2 m tall, with small, white-lilac flowers arranged in whorls, surrounded by showy, colorful pink-purple bracts. The flower stalks are four-angled, thick, and hairy, and the entire plant exudes an intense aroma.

Summary: S. officinalis and S. lavandulifolia are evergreen subshrubs with a woody base and relatively smaller leaves, while S. sclarea is distinguished by its herbaceous habit, much larger leaves and taller inflorescences.

Chemical composition of essential oils

Sage (S. officinalis) essential oil is characterized by a high content of monoterpene ketones—primarily thujone and camphor—as well as 1,8-cineole (eucalyptol). In the Dalmatian chemotype, the main component is α-thujone (up to approximately 25-57% of the composition), followed by camphor and 1,8-cineole (often several to several dozen percent each). For example, in one study, the dominant compounds in S. officinalis oil were: camphor (~33.6%), 1,8-cineole (~22.2%), α-thujone (~21.4%), followed by camphene (~4.9%) and β-thujone (~4%). Spanish sage oil (S. lavandulifolia) has a different profile – it contains significantly less thujone, but is rich in 1,8-cineole (according to various analyses, 15-55% of the composition), as well as camphor and pinene. Both sages produce oils rich in monoterpenes, but S. lavandulifolia is of the cineole-camphor chemotype, while S. officinalis is of the thujone-camphor chemotype .

Clary sage oil (S. sclarea), on the other hand, differs fundamentally – it is dominated by the linalyl ester, linalyl acetate, and the terpene alcohol linalool. Depending on the oil's origin, linalyl acetate can constitute approximately 50-75% of the composition, with linalool another 15-30%. Other components include other esters (e.g., geranyl acetate), alcohols (α-terpineol), and sesquiterpenes (germacrene D). Clary sage oil contains virtually no thujone , thus devoid of the neurotoxic properties characteristic of S. officinalis. It is distinguished by the presence of the diterpene sclareol, which, although present in small amounts (~1-4%), is valued as a precursor to ambroxide in the perfume industry.

In obstetric practice, clary sage oil (Salvia Sclarea) is typically used only towards the end of pregnancy (from 38-40 weeks) or during labor. Earlier stages of pregnancy : No scientific data are available, but as a precaution, most sources recommend avoiding strong emmenagogue oils during this period. Despite the lack of evidence, aromatherapists often advise against using clary sage during the first and second trimesters (unless in very low concentrations), fearing the theoretical risk of uterine stimulation. It should be emphasized that this recommendation is based more on tradition and caution than on documented cases – there have been no published reports of miscarriages induced by clary sage aromatherapy . Tisserand and Young (2014) clearly state that there is no evidence of toxicity or teratogenicity of clary sage oil during pregnancy, and that the contraindications are precautionary in nature ( roberttisserand.com) .

In summary, the chemotype of S. sclarea is primarily ester-alcoholic (with an aroma similar to lavender oil), while both species of Sage (officinalis and lavandulifolia) contain mainly ketone and oxidic compounds (thujone, camphor, cineole) .

Therapeutic use

Effects on the nervous system: Both common sage and Spanish sage are known for their beneficial effects on cognitive function. Their oils and extracts have been shown to inhibit acetylcholinesterase in the brain (which promotes increased cholinergic transmission). S. lavandulifolia oil selectively inhibited AChE in vitro with an IC₅₀ = 0.03 µg/ml , with 1,8-cineole and α-pinene identified as the main active ingredients. Clinical studies have confirmed the procognitive effect – in several trials involving young adults, administration of sage oil or dried sage (common or Spanish) improved memory (e.g., word recall), concentration, as well as subjective mood and arousal . A meta-analysis (Miroddi et al. 2014) showed that S. officinalis and S. lavandulifolia preparations improve cognitive performance in both healthy individuals and patients with dementia . Furthermore, in a 4-month, randomized, double-blind study in 42 patients with Alzheimer's disease, sage extract significantly improved ADAS-cog scores compared to placebo (p = 0.03), without significant adverse effects. While clary sage has not been extensively studied for its effects on memory, it is known for its anxiolytic and antidepressant effects. Its essential oil has a relaxing effect – inhalation in menopausal women reduced cortisol levels by 36% (in the group prone to depression) and increased serotonin (5-HT) levels in the blood. The feeling of relaxation after aromatherapy with clary sage was confirmed subjectively and in animal models (in tests on rats, the oil showed antidepressant effects by modulating the dopaminergic system).

Effects on the Endocrine System: In traditional medicine, sage was valued as a "feminine" plant. For example, infusions of sage leaves were used to alleviate excessive sweating and hot flashes in menopausal women (antihydrotic effect), as well as to inhibit lactation after childbirth. Sage's hormonally regulating, estrogen-like effects are widely believed, with reports of beneficial effects on premenstrual syndrome and menopausal symptoms. Contemporary research suggests that certain compounds (e.g., sclareol from S. sclarea) may bind to estrogen receptors, although their actual effect in the body is weak or indirect. Despite this, clary sage oil is widely used in aromatherapy to alleviate menstrual and menopausal symptoms – it relaxes smooth muscles (spasmolytic effect), improves mood and hormonal balance, and is sometimes used to stimulate uterine contractions in delayed labor (due to the possible stimulation of oxytocin secretion). Despite its high thujone content, sage has also been historically described as a plant with cycle-regulating properties – it alleviated painful periods and tension (hence the English name "clary sage" initially referred to S. sclarea, but certain "clarifying" properties were attributed to the entire Salvia genus). Currently, S. sclarea is more often recommended for women's ailments, while S. officinalis is recommended for menopausal symptoms (for example, in studies, sage extract reduced the frequency of hot flashes and excessive sweating in menopausal women).

Antibacterial and Other Effects: All three species discussed exhibit antimicrobial and anti-inflammatory properties typical of the Salvia genus. Sage is particularly versatile here – its leaves also contain phenolic compounds (e.g., rosmarinic acid, carnosol) with antioxidant and anti-inflammatory effects, and the entire raw material has astringent, disinfectant, and digestive (improves digestion) properties. Sage oil has bactericidal and fungicidal effects: it inhibits the growth of many pathogens (staphylococci, streptococci, E. coli , Candida , etc.), although Pseudomonas aeruginosa , for example, shows some resistance. In vitro, S. officinalis and S. lavandulifolia oils demonstrated bactericidal activity even at low concentrations against Proteus mirabilis and Bacillus subtilis , and also inhibited S. aureus and Candida albicans (albeit at slightly higher doses). Thujone, camphor, 1,8-cineole, and phenols (for example, thujone also has a virus-inhibiting effect) are responsible for its antimicrobial properties. Thanks to its high linalool content , nutmeg sage also has antiseptic properties (linalool is a well-known antibacterial and antifungal agent). Furthermore, it exhibits adstringent properties (astringent and healing properties)—hence, this oil is often added to cosmetics for oily and acne-prone skin. All sages also have antispasmodic effects (on the smooth muscles of the digestive tract and bronchi), diaphoretic effects, and expectorant effects (facilitating expectoration in respiratory infections). When taken internally (e.g., as a decoction), sage reduces diarrhea and flatulence (improves digestion through its eupeptic effect). However, when applied externally (rinses, compresses), it has a disinfecting effect - sage infusion is traditionally used to gargle in cases of tonsillitis and to wash wounds that are difficult to heal.

Safety of use and toxicity

Sage (S. officinalis) contains significant amounts of thujone, a potentially neurotoxic compound. Thujone acts as an antagonist of GABA_A receptors in the central nervous system, negating the inhibitory effects of GABA, which in excess can cause neuronal excitation and seizures. Cases of epileptic seizures following an overdose of sage oil have been reported. For example, an infant and a small child experienced generalized tonic-clonic seizures after accidental ingestion of S. officinalis oil . Therefore, pure sage oil should not be taken orally, and in aromatherapy and cosmetics, it must be used in high dilution. Preparations containing this sage are contraindicated in people with epilepsy. Pregnant and breastfeeding women should also avoid sage , as thujone crosses the placental barrier and is found in breast milk. Furthermore, there are traditional reports of the possible abortifacient effects of very high doses of this plant. It's worth noting that Spanish sage (S. lavandulifolia) , despite its close relationship, contains negligible amounts of thujone, making its oil considered safer from a neurotoxic perspective. In practice, this oil is sometimes recommended as a milder substitute for sage oil —while retaining its pro-cognitive and antibacterial properties, it lacks the convulsant risk typical of thujone. Clary sage (S. sclarea) also does not contain thujone , and the main components of its oil (linalyl acetate, linalool) have relatively low toxicity . This oil is well tolerated; only sporadic allergic reactions (e.g., in individuals sensitive to terpene esters and alcohols) or mild narcotic effects at very high concentrations (excessive drowsiness, headaches) have been reported. Overall, however, S. sclarea is considered one of the safest sages in aromatherapy. Regardless of the species, all sage essential oils should be used in moderation – high doses can irritate mucous membranes and skin (oils rich in thujone and camphor are highly irritating). In the case of children, it is recommended to avoid direct administration of sage oils (especially S. officinalis ), and in breastfeeding women, drinking sage infusions can be used to stop lactation, but such treatment should be short-term and under the supervision of a specialist.

Data from scientific research

• Enzymatic activity (in vitro): Sage oils have been shown to inhibit enzymes associated with neurodegenerative processes. For example, Salvia lavandulifolia oil inhibits acetylcholinesterase with an IC₅₀ of 0.03 µg/ml , confirming its potential to enhance memory (by increasing acetylcholine in the brain). Sage extracts also inhibit AChE and exhibit antioxidant properties in vitro , thanks to the presence of polyphenols and terpenes.
• Clinical studies (memory and cognition): A systematic review of 6 human studies found that administration of S. officinalis or S. lavandulifolia preparations improved short-term memory, attention, and mood in both young healthy individuals and patients with mild dementia. In one of these studies, healthy adults, after a single dose of Spanish sage oil, improved their word recall scores by more than 10 percent compared to placebo. In a study of Alzheimer's disease patients, 4 months of supplementation with S. officinalis extract reduced the ADAS-cog score by 1.6 points compared to a 0.7-point decline in the placebo group (statistically significant difference; p=0.03). Simultaneously, a lower incidence of agitation and neuropsychiatric symptoms was observed in patients taking sage.
• Clinical studies (stress and hormones): A randomized trial of 22 menopausal women showed that inhalation of nutmeg sage oil significantly reduced blood cortisol levels (by an average of 16-36%, depending on baseline stress levels) and increased serotonin (5-HT) levels , which correlated with an anxiolytic effect and improved mood. In another study in rats, this oil demonstrated antidepressant effects , increasing exploration in a forced swimming test—a mechanism linked to modulation of dopamine receptors in the brain. Furthermore, two weeks of supplementation with sage leaf extract in women with hyperprolactinemia resulted in a ~15% decrease in prolactin levels and resolution of galactorrhea symptoms (although this was a pilot study without a control group). These observations support the folk use of sage as a hormone-normalizing agent.
• Antioxidant and antimicrobial properties: Sage oils exhibit strong antioxidant activity in vitro . In the DPPH test, S. lavandulifolia oil neutralized approximately 93% of free radicals , while S. officinalis oil neutralized ~75% (for comparison, the standard BHT antioxidant achieved ~95%). In the FRAP test, however, sage oil demonstrated higher potential (72% versus 65% for Spanish sage). Both oils also demonstrated strong antimicrobial activity – inhibiting the growth of the Gram(negative) bacteria Proteus mirabilis and Gram(positive) Bacillus subtilis at a concentration of 0.5 mg/ml, and exerting a biocidal effect on Staphylococcus aureus and the yeast Candida albicans at a concentration of 2 mg/ml. These effects support sage's traditional uses as a disinfectant and food preservative. Moreover, thanks to the presence of rosmarinic acid and carnosol, sage leaf extracts have demonstrated cytoprotective effects in cell models—protecting nerve cells from oxidative stress and inhibiting the formation of amyloid deposits (important in the pathogenesis of Alzheimer's disease). These multifaceted properties make sage a promising phytotherapeutic resource, as reflected in the growing number of scientific studies devoted to these plants.

Sources: en.wikipedia.org, https://pubmed.ncbi.nlm.nih.gov/24836739/,https://pubmed.ncbi.nlm.nih.gov/12605619/,https://pubmed.ncbi.nlm.nih.gov/24802524/, nature.com/articles/s41598-023-41178-2, https://naha.org/assets/uploads/PregnancyGuidelines-Oct11.pdf,