Salvia sclarea

Salvia sclarea (Clary Sage) is a herb commonly used as an aromatic. Belonging to the Mint family of plants, the 'relaxing' effects of the aromas may be related to preliminary evidence suggesting anti-depressant effects.

This page features 22 unique references to scientific papers.

Summary

All Essential Benefits/Effects/Facts & Information

Salvia Sclarea (Clary Sage) is a herb in the mint family traditionally used as a relaxing agent and aromatic, with a fair bit of literature suggesting it is used for for menopausal women.

There is a lack of large-scale studies to support the usage of Clary Sage as an aromatic, but the evidence that exists currently is supportive. One study in rodents (in which the rodents were essentially hot boxed with Clary Sage) noted anti-depressive effects after a single exposure and one study in female humans has noted a reduction in systolic blood pressure and respiratory rate 60 minutes after inhalation (study was placebo controlled and blinded, as to omit the possibility of the placebo effect).

Two studies exist using combination therapy of Clary Sage, Lavender, and another herb (one study used Rose Essential Oil, the other Marjoram) which have confirmed that this herbal aromatic therapy appears to be more effective than placebo in relieving menstrual pain in persons who self-report that they have more menstrual pain than average (on a scale of 1-10, participants had to rate a 5 or higher to be included in the study).

There are some immunological interactions with may be important to anti-cancer effects, but currently these studies are investigating the activity of the bioactive known as (-)-Sclareol which is unlikely to be located in the aroma. The anti-cancer effects, although interesting, are currently preliminary and not associated with aromatherapy.

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How to Take

Recommended dosage, active amounts, other details

If using Clary Sage for aromatherapy, enough should be lit (if using incense) to confer a pleasant aroma. The two studies using combination therapy noted that a cream containing 1 concentration drop of Clary Sage to 2 drops of Lavender in 5cc of volume was rubbed on the abdomen (the scent would remain on the body for a while).

Due to the exact bioactives not being known, quantifying the right dose for aromatherapy is difficult.

There is insufficient evidence to suggest an optimal oral dose of Clary Sage for any purpose.

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Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects salvia sclarea has on your body, and how strong these effects are.

Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
Blood Pressure Minor Very High See study
A decrease in systolic blood pressure resulted in response to clary sage aromatherapy, to a small degree and likely not able to exert long-term benefit (probably more indicative of short-term CNS depression)
Cortisol Minor Very High See study
A decrease in cortisol may result following inhalation of clary sage, but the magnitude of reduction (2.5%) is very small
Heart Rate Minor Very High See study
A decrease in heart rate has been noted acutely in response to the aroma of clary sage

Studies Excluded from Consideration

  • Omitted due to including Lavender and at least one other aromatic[1][2]


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1Sources and Summary

Salvia sclarea (of the family Lamiaceae; the Mint family), more commonly referred to as Clary Sage, is an aromatic herb. It is used highly in the perfume industry as the main bioactive, (-)-Sclareol, can be synthesized into Ambrox (an aromatic found from naturally in Ambergris, but is rare from its natural source).[3]

It is sometimes drunk as a tea in Turkey, where it is known as misk sage tea.[4]

Clary sage also has usage as an insect repellant.[5]

1.1. Composition

  • The labdane type diterpene (-)-Sclareol, at 0.002-0.026% essential oil but can be up to 1.5% with solid/liquid extraction.[6] The isomer 13-episclareol also exists, with both being biosynthesized from geranylgeranyl diphosphate.[3][7] Sclareol oxide has also been detected[8]

  • Manool and 13-epimanool (as well as the latter's oxide), structurally similar to Sclareol[8]

  • Salviatrienes A and B at 4.5% and 1% of the folded essential oil[8]

  • E,E-α-farnesene[8]

  • Salvipisone[9]

  • Aethiopinone[9]

  • α-eudesmol, δ-cadinene, and δ-amorphene (aromatics)[8]

The seeds of Clary sage have a 17.66+/-0.11% protein content and 27.24+/-1.32% essential oil content with 5.23+/-0.04% ash content.[4] The fatty acid composition is mostly α-linoleic acid (C18:3 n3) at 52.1+/-0.04% of fatty acids and oleic acid (C18:1 n9) at 22.05+/-0.01%.[4]


2Neurology

2.1. Neuroprotection

The antioxidant potential of Clary Sage in vitro is thought to exert neuroprotective effects, although it underperformed relative to other species of Salvia in protecting neuronal cells from DNA damage.[10]

2.2. Depression

The essential oil of Clary Sage, following either intraperitoneal injection (0.05-0.2mL essential oil per kg bodyweight) or inhalation (1mL essential oil in warm water to release the aroma) to rats, showed anti-depressant actions in a Forced Swim Test model with a potency greater than that of Anthemis nobilis (Chamomile), Rosmarinus officinalis (Rosemary), and Lavandula angustifolia (Lavender) and comparable to the active controls of Imipramine (30mg/kg) and fluoxetine (1.8mg/kg); this anti-depressant effect was blocked with dopamine antagonists and buspirone, a serotonin receptor (5-HT1A) antagonist.[11] When serum corticosteroids were measured (to assess the stress response), there was no significant effect of Clary Sage.[11]

Appears to have anti-depressant effects in rats, and this has been noted with the aroma of Clary Sage

2.3. Pain

In 61 college-aged females with higher than average menstrual pain (6-10 on a VAS rating scale), an abdominal massage with 2 drops of Lavandula officinalis (Lavender) to one drop Clary Sage and one drop Rosa centifolia (Rose Essential Oil) was compared to placebo aromatherapy (almond oil, same method of appplication and volume of 5cc) and control (no aromatherapy). It was noted that aromatherapy was associated with an average reduction in pain from 7 (0-10 rating scale) down to 5 and then 3 on days 1 and 2, respectively; control failed to reduce pain, and placebo aromatherapy appears to work in some persons to a lesser extent than combination therapy (herb intervention still significantly greater than the placebo group).[1] The authors noted that although heavier flows appears to be correlated with greater pain,[12] that there were no significant difference between groups.[1] A similar application method with a similar aromatherapy (Rose switched for Origanum majorana; Marjoram) noted that in persons with diagnosed primary dysmenorrhea given aromatherapy (placebo given synthestic scents; different molecules) that the herbal aromatherapy group experienced significantly greater pain relief associated with menstrual symptoms.[2]

The latter study noted that the majority or aromatics were five molecules; linalyl acetate (36.84%), linalool (22.53%), eucalyptol (17.21%), β-caryophyllene (2.69%), and α‐terpineol (3.29%). It is thought that these aromatics are likely to mediated the anaglesic effects noted.[2]

Combination therapy with at least Clary Sage and Lavender appears to be effective in reducing menstrual pain (no indiciation if this extends to pain in general or just menstrual pain), but currently no studies use Clary Sage in isolation and thus its efficacy in isolation cannot be determined


3Cardiovascular Health

3.1. Blood Pressure

One study using Salvia Sclarea essential oil vapors (aromatherapy) in females with urinary incontinence undergoing urodynamic assessment noted that inhalation of Salvia Sclarea for 60 minutes was associated with a drop in systolic blood pressure relative to plcebo (almond oil), a drop in diastolic relative to Lavender scent but not placebo, and a decrease in respiratory rate relative to placebo.[13] The drop in diastolic, which was not statistically significant relative to placebo, was because Lavender trended to increase blood pressure slightly.[13]

At least one study to support Clary Sage reducing blood pressure via aromatherapy


4Interactions with Cancer Metabolism

4.1. Immunological Interactions

CD4+CD25+ T-cells are produced in the thymus[14] or in the periphery via conversion from other T-cells[15] and express Foxp3+ to positively influence development and function.[16] CD4+CD25+ may accumulate at the site of tumors[17] where they suppress the activity of cytotoxic T-cells[18]

In mice bearing breast tumors who were then given an injection of isolated Sclareol (7.85mcg daily) directly into the tumor noted that the tumor did not grow in volume, while control experienced a standard growth rate; this was associated with an increase in IFN-γ with a concomitant decrease in IL-4 and reduced levels of the CD4+CD25+Foxp3+ Treg (T regulatory) immune cell.[19] The suppression of CD4+CD25+Foxp3+ Treg cell concentration is thought to preserve T-cell mediated cytotoxicity towards tumor cells, and was as effective as the active control of Cyclophosphamide.[19]

May have mechanisms to preserve T-cell cytotoxicity towards tumor cells via reducing the levels of a suppressive T-cell

4.2. Colon

HCT116 tumor-bearing mice appear to have reduced tumor size in response to injections of Sclareol (following liposomal incorporation, 1100mg/kg over 5 days with 50% dosing decrements),[20] and suppression of HCT116 tumors has been noted elsewhere in immunodeficient mice.[21]

4.3. Leukemia

Sclareol has been noted to induce apoptosis in B and T lymphocytic tumor cells with an IC50 below 20µg/mL via apoptotic means.[22] This general cytotoxcity appears to extend to most cancer cell lines testes, and one study using CCRF-CEM leukemic cells as well as normal immune cells (resting and PMA activated PMBCs) noted that free sclareol did not show any therapeutic index (GI50 between 33.1-35µM) while liposomal sclaerol had a GI50 of less than 15µM on leukemic cells and over 100µM on normal cells.[20]

Scientific Support & Reference Citations

References

  1. Han SH, et al Effect of aromatherapy on symptoms of dysmenorrhea in college students: A randomized placebo-controlled clinical trial . J Altern Complement Med. (2006)
  2. Ou MC, et al Pain relief assessment by aromatic essential oil massage on outpatients with primary dysmenorrhea: a randomized, double-blind clinical trial . J Obstet Gynaecol Res. (2012)
  3. Günnewich N, et al A diterpene synthase from the clary sage Salvia sclarea catalyzes the cyclization of geranylgeranyl diphosphate to (8R)-hydroxy-copalyl diphosphate . Phytochemistry. (2012)
  4. Yalcin H, et al Effect of γ-irradiation on bioactivity, fatty acid compositions and volatile compounds of clary sage seed (Salvia sclarea L.) . J Food Sci. (2011)
  5. Conti B, et al Repellent effect of Salvia dorisiana, S. longifolia, and S. sclarea (Lamiaceae) essential oils against the mosquito Aedes albopictus Skuse (Diptera: Culicidae) . Parasitol Res. (2012)
  6. Caissard JC, et al Extracellular localization of the diterpene sclareol in clary sage (Salvia sclarea L., Lamiaceae) . PLoS One. (2012)
  7. Caniard A, et al Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L.) and their relevance for perfume manufacture . BMC Plant Biol. (2012)
  8. Laville R, et al Amphilectane diterpenes from Salvia sclarea: biosynthetic considerations . J Nat Prod. (2012)
  9. Walencka E, et al Salvipisone and aethiopinone from Salvia sclarea hairy roots modulate staphylococcal antibiotic resistance and express anti-biofilm activity . Planta Med. (2007)
  10. Asadi S, et al In vitro antioxidant activities and an investigation of neuroprotection by six Salvia species from Iran: a comparative study . Food Chem Toxicol. (2010)
  11. Seol GH, et al Antidepressant-like effect of Salvia sclarea is explained by modulation of dopamine activities in rats . J Ethnopharmacol. (2010)
  12. Sundell G, Milsom I, Andersch B Factors influencing the prevalence and severity of dysmenorrhoea in young women . Br J Obstet Gynaecol. (1990)
  13. Seol GH, et al Randomized Controlled Trial for Salvia sclarea or Lavandula angustifolia: Differential Effects on Blood Pressure in Female Patients with Urinary Incontinence Undergoing Urodynamic Examination . J Altern Complement Med. (2013)
  14. Mahvi DM, et al Intratumoral injection of IL-12 plasmid DNA--results of a phase I/IB clinical trial . Cancer Gene Ther. (2007)
  15. Sakaguchi S, et al Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases . J Immunol. (1995)
  16. Hori S, Nomura T, Sakaguchi S Control of regulatory T cell development by the transcription factor Foxp3 . Science. (2003)
  17. Fukaura H, et al Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients . J Clin Invest. (1996)
  18. Woo EY, et al Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer . Cancer Res. (2001)
  19. Noori S, et al Sclareol modulates the Treg intra-tumoral infiltrated cell and inhibits tumor growth in vivo . Cell Immunol. (2010)
  20. Hatziantoniou S, et al Cytotoxic and antitumor activity of liposome-incorporated sclareol against cancer cell lines and human colon cancer xenografts . Pharmacol Res. (2006)
  21. Dimas K, et al Sclareol induces apoptosis in human HCT116 colon cancer cells in vitro and suppression of HCT116 tumor growth in immunodeficient mice . Apoptosis. (2007)
  22. Dimas K, et al The effect of sclareol on growth and cell cycle progression of human leukemic cell lines . Leuk Res. (1999)