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. 2025 Jan 22:12:1523441.
doi: 10.3389/fmed.2025.1523441. eCollection 2025.

Differential effects of clary sage (Salvia sclarea L.) oil and linalyl acetate on depression levels in diabetic foot ulcer patients with T2DM: a randomized blinded controlled trial

Ji Won Son #  1 , Purum Kang #  2 , Sun Seek Min  3 , Geun Hee Seol  1   4
Affiliations

Differential effects of clary sage (Salvia sclarea L.) oil and linalyl acetate on depression levels in diabetic foot ulcer patients with T2DM: a randomized blinded controlled trial

Ji Won Son et al. Front Med (Lausanne). .

Abstract

Background: Diabetic foot ulcer (DFU) is a significant global health concern due to its substantial burden on individuals and healthcare systems. In addition to its physical impact, DFU has emotional effects on patients. This study analyzed the effects of inhaling clary sage (CS; Salvia sclarea L.) or linalyl acetate (LA) on depression and psychological factors in patients with DFU.

Methods: This study, performed at the Diabetic Wound Center, enrolled DFU patients, categorized as having mild or moderate to severe depression based on visual analog scale (VAS) for depression scores. Patients were randomized to inhalation of 5% CS oil, 5% LA or almond oil (control) by natural breathing. Blood pressure, heart rate, Depression-VAS, Anxiety-VAS, and Stress-VAS were measured before and after inhalation.

Results: This study enrolled 72 patients with DFU, including 43 with mild and 29 with moderate to severe depression. Of the 43 patients with mild depression, 14, 14, and 15 were randomized to inhalation of CS, LA, and almond oil, respectively. Of the 29 patients with moderate to severe depression, 9, 11, and 9 were randomized to inhalation of CS, LA, and almond oil, respectively. Compared with inhalation of almond oil, inhalation of CS oil significantly reduced stress (p < 0.05) and (p < 0.01) in patients with mild depression, whereas inhalation of LA significantly reduced anxiety-VAS (p < 0.05) and depression-VAS (p < 0.05) in patients with moderate to severe depression.

Conclusion: Inhalation of CS oil may have the potential to alleviate stress and anxiety in DFU patients with mild depression, whereas inhalation of LA may have the potential to alleviate anxiety and depression in DFU patients with moderate to severe depression. These findings suggest that adjunct therapy in DFU patients should be individualized according to the degree of depression.

Clinical trial registration: http://cris.nih.go.kr/, identifier KCT0009722.

Keywords: clary sage; complementary and alternative medicine; depression; diabetic foot ulcer; linalyl acetate.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Recruitment and randomization. CS, clary sage; LA, linalyl acetate.
Figure 2
Figure 2
Total ion chromatogram of clary sage oil derived from gas chromatography–mass spectrometry data.
Figure 3
Figure 3
Effects of inhalation of clary sage oil (CS) or linalyl acetate (LA) on (A) systolic blood pressure (SBP), (B) diastolic blood pressure (DBP), (C) mean arterial pressure (MAP), and (D) heart rate (HR) in DFU patients with mild depression. Results are presented as mean ± standard error of the mean. ##p < 0.05, ###p < 0.01 vs. pretreatment; **p < 0.05 vs. Control.
Figure 4
Figure 4
Effects of inhalation of clary sage oil (CS) or linalyl acetate (LA) on (A) systolic blood pressure (SBP), (B) diastolic blood pressure (DBP), (C) mean arterial pressure (MAP), and (D) heart rate (HR) in DFU patients with moderate to severe high depression. Results are presented as mean ± standard error of the mean. ##p < 0.05 vs. pretreatment.
See this image and copyright information in PMC

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