Frostbite is a cold-induced thermal injury that arises when tissues are subjected to temperatures lower than their freezing threshold [1]. The severity of frostbite can vary considerably, from minor tissue damage with mild long-term consequences to severe necrosis, requiring amputation [2]. Long-term complications from frostbite may include extensive tissue destruction, ischemia, and other potentially irreversible effects, which can lead to amputation or even death in severe cases [3]. The current approach for treating frostbite is rapid rewarming [4]. In addition, several pharmacological interventions are commonly employed, such as iloprost, nonsteroidal anti-inflammatory drugs, heparins, antibiotics, antiplatelet agents, and dextran [5].

In Zhang et al.’s [6] study on the pathological mechanism and treatment of frostbite, they mentioned Chinese medicine treatment for managing this condition. In addition, the Surgical Branch of the China Association of Chinese Medicine has issued guidelines for the application of Chinese medicine in the diagnosis and management of frostbite [7].

However, to date, no study has investigated Korean medicine treatments for frostbite. Therefore, the present study aimed to explore the efficacy of Korean medicine treatments for managing frostbite through a review of literature of related clinical and animal studies.

1. Databases and search methods

We conducted a comprehensive search for clinical and experimental studies pertaining to Korean medicine for frostbite in the following databases from January 1, 2000, to August 15, 2024: PubMed, Cochrane Library, EMBASE, Korean Studies Information Service System (KISS), Research Information Sharing Service (RISS), Oriental Medicine Advanced Searching Integrated System (OASIS), and China National Knowledge Infrastructure (CNKI). The literature search terms included “frostbite*,” “acupuncture,” “needl*,” “electroacupuncture,” “herbal medicine,” and “Korean medicine.”

2. Inclusion and exclusion criteria

The present study searched for both animal and human studies assessing the impact of Korean medicine on frostbite. The interventions covered a range of Korean medicine treatments, including acupuncture, electroacupuncture (EA), herbal medicine, moxibustion, and bloodletting. The exclusion criteria included duplicate studies, studies without a full text, studies published in non-academic medical journals, and studies that did not involving Korean medicine treatments. After screening the titles and abstracts to eliminate clearly irrelevant studies, the full texts were reviewed to confirm their eligibility.

1. Study search results

Altogether, 196 studies were retrieved from PubMed (n = 17), EMBASE (n = 22), Cochrane Library (n = 5), RISS (n = 19), KISS (n = 13), OASIS (n = 0), and CNKI (n = 120). The articles were screened, and the full texts were assessed according to the exclusion and inclusion criteria. As a result, four studies were selected for the final review (Fig. 1).

Figure 1. Flowchart of the study selection process. RISS, Research Information Sharing Service; KISS, Korean Studies Information Service System; OASIS, Oriental Medicine Advanced Searching Integrated System; CNKI, China National Knowledge Infrastructure.

2. Analysis of clinical studies

Among the four studies, two studies involved human subjects and both of them were case studies. The analyses of these case studies are presented in Table 1 and 2.

Table 1 . Characteristics of the included clinical studies.

Study, y	Study design	Patient information
		Sex/age (y)	Injured area	Frostbite grade	Treatment duration (d)
Ha et al. [8], 2024	Case report	M/45	Nose, left ear	Grade 3	53 (27 visits)
		M/27	Both the first, second, and third toes	Grade 3	78 (38 visits)
		M/46	Right first toe left first and third toes	Grade 3	91 (45 visits)
			The rest of the toes	Grade 2
Norheim and Alræk [9], 2018	Case report	F/19	Right first, third, and fourth fingers and left third and fourth fingers	Grade 2	84 (12 visits)
			The rest of the fingers	Grade 1

M, male; F, female..

Table 2 . Interventions, evaluation, and results of the included case reports.

Study, y	Intervention			Evaluation	Result
	Acupuncture	Herbal medicine	Other
Ha et al. [8], 2024	1. Local acupoints - Positioned around the affected area at 0.3-cm intervals - At each visit 2. Distal acupoints - LI4, LI5, LI10, LI11, TE4, LR3, SI3, SI5, TE5, PC6, PC7, SP6, SP10, KI3, GB40, ST36, and BL60 - At each visit	Danggwisayeokgaohsuyusaenggang-tang - Two doses of 120 cc/day	1. Bloodletting - Three sites along the periphery of the lesion - 10 mL of blood extracted at each site - At each visit 2. Direct moxibustion - Three layers of moxa positioned around the perimeter at 0.5-cm intervals - At each visit 3. Herbal ointments - Jaungo was used for the dressing - At each visit	Clinical symptoms	- Full resolution of the affected area, including restoration of the skin color, sensory perception, and functionality - No additional medical intervention required
Norheim and Alræk [9], 2018	- LR3, LI4, ST36, and KI7 - Once a week for 12 weeks	-	-	DIRT	Increase in the skin temperature

-, not available; DIRT, dynamic infrared thermography..

3. Patient information

In Ha et al.’s [8] study, three patients were diagnosed with third-degree frostbite according to the extent of tissue damage sustained following alpine climbing in the Himalayas. None of the patients had undergone time- sensitive treatments, including prostacyclin or thrombolysis. All patients were advised to undergo partial amputation in conventional medical facilities.

In Norheim and Alræk’s [9] study, one patient was diagnosed with second-degree frostbite on both fingertips. During outdoor military exercises, amidst the severe climate of Northern Norway, she noticed a gradual loss of sensation in her fingers, which later developed a dark discoloration accompanied by blisters. Although she had spontaneous healing, she continued to experience sensory-motor disturbances and an increased sensitivity to cold at the 1-year follow-up.

4. Treatment method and evaluation

In Ha et al.’s [8] study, after receiving emergency treatment, the patients opted for Korean medicine treatments, including acupuncture, herbal medicine, direct moxibustion, and bloodletting, instead of partial amputation. All patients exhibited remarkable recovery of the damaged tissue, eliminating the need for amputation. No side effects or complications were noted. Frostbite was considered clinically resolved when the affected area fully recovered, including the restoration of function, sensation, and skin color, with no additional medical treatment necessary. Safety evaluation of the treatment revealed no adverse reactions, such as discomfort, infection, or pain, or worsening of the condition in all three cases.

In Norheim and Alræk’s [9] study, specific acupuncture points (LR3, LI4, ST36, and KI7) were selected to improve peripheral blood circulation. The acupuncture sessions were conducted once a week for 12 weeks. Dynamic infrared thermography (DIRT) was employed to show the microvascular effects induced by acupuncture. Thermographic images were captured and skin temperature was measured at three stages: at the time of injury, prior to the start of acupuncture treatment, and after completing 12 weeks of acupuncture treatment. The average temperatures across all 10 fingers were increased progressively at each of the three time points.

5. Analysis of the included animal studies

Two studies were animal experiments, and the analysis of these studies is presented in Table 3.

Table 3 . Characteristics of the included animal studies.

Study, y	Model	Sample size	Intervention	Evaluation	Result
Kong et al. [10], 2023	C57/BL6 mice (8–10 weeks old, 20–25 g, SPF grade)	(A) n = 18 (B) n = 18 (C) n = 18	(A) Frostbite group (frostbite mice without EA) (B) Frostbite + EA group (frostbite mice with EA) (C) Sham group	(1, 2) Hematoxylin-eosin and Masson staining (3) ELISA (4) Western blot	(1) Mean wound area (mm2) ↓ (p < 0.05) (2) More complete and clearer skin tissue structure, levels of collagen ↑ (3) TXB2/6-keto-PGF1α ratio ↓ (p < 0.05) (4) IL-1β, NF-κB, TLR4, TNF-α protein levels in the skin tissue ↓ (p < 0.05)
Li et al. [11], 2010	Wistar mice (220–240 g, SPF grade)	(A) n = 10 (B) n = 10 (C) n = 10 (D) n = 10 (E) n = 10	(A) Untreated frostbite group (B) Oral HGWD (C) Soak HGWD (D) Oral-soak HGWD (E) Normal control group	ELISA	(1) IL-6: A > B (p < 0.05), A > C (p > 0.05)/ B, C > D (p > 0.05) (2) TNF-β: A > B (p < 0.01), A > C (p < 0.05), C > B (p < 0.01)/ B, C > D (p < 0.05) (3) TXB2: A > B (p > 0.05), A > C (p > 0.05)/ B, C > D (p > 0.05) (4) 6-keto-PGF1α: A < B (p < 0.01), A < C (p > 0.05)/ B, C < D (p < 0.05)

SPF, specific-pathogen-free; EA, electroacupuncture; ELISA, enzyme-linked immunosorbent assay; TXB2, thromboxane B2; 6-keto-PGF1α, 6-ketoprostaglandin F1α; IL, interleukin; NF-κB, nuclear factor kappa B; TLR4, toll-like receptor 4; TNF, tumor necrosis factor; HGWD, Huangqi Guizhi Wuwu Decoction..

6. Methods

In Kong et al.’s [10] study, mice were randomly assigned to the sham, frostbite, and frostbite + EA groups. A sham group was included to monitor for any variations that could arise from the use of anesthesia or placement of magnets. The mice with frostbite mice in the group received EA treatment (2-Hz frequency and 1-mA intensity) for 30 minutes daily over a period of 21 days. Acupuncture needles (0.167 mm in diameter) were inserted into a depth of 2 mm at the LI11, SP10, and ST36 acupoints.

In Li et al.’s [11] study, the mice were randomly allocated into the normal control, untreated frostbite, frostbite + oral Huangqi Guizhi Wuwu Decoction (HGWD), frostbite + soak HGWD, and frostbite + oral-soak HGWD groups. Ten mice in the normal control group were allowed to grow naturally without any intervention. In the experimental group, frostbite was induced by soaking the feet in a mixture of 800 mL of water and 400 mL of ethanol at a temperature of −2℃ for 1 minute and 30 seconds. Based on the appearance of localized erythema and edema, the frostbite was classified as first-degree. In some mice (approximately 8%), dermal damage and blister formation led to the classification of second-degree frostbite. The untreated frostbite group received no treatment. The oral administration group (oral HGWD) was administered 4.7 g of HGWD twice daily via gavage. The soak HGWD group immersed their feet in HGWD (17℃ ± 2℃ and 30 minutes daily) to a level above the ankles at the same concentration as in the oral HGWD group. The oral-soak HGWD group underwent both gavage administration and foot immersion. All treatments were administered continuously for 3 days across all groups. After the treatment period, the samples were collected from all groups, and the serum was separated to measure the 6-ketoprostaglandin F1α (6-keto-PGF1α), thromboxane B2 (TXB2), tumor necrosis factor-β (TNF-β), and interleukin-6 (IL-6) levels using an enzyme-linked immunosorbent assay (ELISA).

7. Evaluation

In Kong et al.’s [10] study, the mean wound area in frostbite rats treated with EA was significantly reduced (p < 0.05) as compared with that in untreated frostbite rats. At 3 weeks post-frostbite, the skin tissue structure was more intact and defined with higher collagen levels in the frostbite + EA group as compared to those of the frostbite group. Additionally, after EA treatment, there was a significant reduction in the protein levels of nuclear factor kappa B (NF-κB), IL-1β, toll-like receptor 4 (TLR4), and TNF-α in the skin tissue, as well as a decrease in the TXB2/6-K-PGF1α ratio in the serum of frostbite rats (p < 0.05).

In Li et al.’s [11] study, the serum IL-6, TXB2, and TNF-β levels were significantly elevated (p < 0.01), whereas the 6-keto-PGF1α levels were significantly reduced (p < 0.01) in the untreated group as compared to those of the normal control group. Oral HGWD treatment significantly decreased the serum IL-6 levels (p < 0.05); however, no significant change was observed in the soak HGWD group (p > 0.05), and no interaction was found between the two administration methods in terms of IL-6 regulation (p > 0.05). Both oral and soak HGWD treatments led to a significant reduction in TNF-β levels (p < 0.01 and p < 0.05, respectively), with an interaction observed between the two methods. The oral HGWD group showed a significantly lower TNF-β level than the soak HGWD group (p < 0.01). No significant reduction in the TXB2 levels was observed in either the oral or soak HGWD groups as compared with the untreated group (p > 0.05), and no interaction between the administration methods was detected (p > 0.05). The oral HGWD treatment resulted in a significant increase in the 6-keto-PGF1α levels (p < 0.01), whereas no significant change was noted in the soak HGWD group (p > 0.05). An interaction between the two administration methods was observed in the regulation of 6-keto-PGF1α (p < 0.05).

Frostbite is a severe ischemic injury that develops as a result of tissue vascular damage due to exposure to subzero temperatures. It mainly occurs in the exposed peripheral parts of the body [12]. A commonly employed four-tier classification system offers immediate guidance during clinical assessment and can be simplified by merging levels 1 and 2 to denote superficial frostbite and merging levels 3 and 4 to denote deep frostbite [5].

First-degree frostbite involves partial freezing of the skin characterized by hyperemia, erythema, and edema without the presence of necrosis or blisters. Intermittent skin may present 5–10 days after the initial injury. Second-degree frostbite is characterized by full-thickness skin freezing, accompanied by erythema, pronounced edema, and clear fluid-filled vesicle and blister formation, which may subsequently lead to desquamation and black eschar development. Third-degree frostbite involves the complete freezing of the subcutaneous tissue and skin, with clinical manifestations such as hemorrhagic blisters or violaceous, blue-gray discoloration, and skin necrosis. Fourth-degree frostbite is characterized by the complete freezing of the skin, subcutaneous tissue, tendon, muscle, and bone, initially presenting with minimal edema and a mottled, cyanotic or deep red appearance that later progresses to a dry, black, and mummified state [2]. In traditional medicine, frostbite is understood to occur when cold energy invades from the outside or when an individual with a constitutionally deficient yang energy is exposed to external cold, leading to the condensation of cold in the skin, failure to maintain warmth, obstruction of blood vessels, stagnation of qi and blood, and blockage of the meridians [7].

Adjunctive treatments in prehospital and hospital settings include hyperbaric oxygen, iloprost, nonsteroidal anti-inflammatory drugs, heparin, antibiotics, dextran, tetanus toxoid, immune globulin, antiplatelet agents, empirical fasciotomy, sympathetic blockade, and more [5]. However, due to the considerable risk of adverse reactions, including allergies and drug resistance associated with these treatments, there is a growing interest in exploring non-pharmacological therapies that may enhance wound healing [13]. Sympathectomy (nerve block) and hyperbaric oxygen therapy are among the proposed non-drug treatments [14].

Korean medicine treatments, such as acupuncture, EA, moxibustion, and herbal medicine, may also be considered an alternative therapy for frostbite. Acupuncture has been reported to promote healing and alleviate pain and inflammation by stimulating the release of neurotransmitters and hormones, as well as enhancing the production of growth factors involved in neovascularization and tissue growth [15,16]. Therefore, it is considered that the treatment may enhance circulation to the affected region, facilitating the delivery of oxygen and essential nutrients, which support tissue healing and regeneration. Moreover, it is deemed that these acupuncture mechanisms have shown considerable efficacy in the treatment of frostbite. EA has demonstrated substantial effectiveness in alleviating visceral pain, cancer-related pain, nerve damage, and persistent tissue damage [17]. In addition, direct moxibustion may enhance blood circulation, thereby facilitating wound healing and promoting tissue regeneration [18]. Danggwisayeokgaohsuyusaenggang-tang used in Ha et al.’s [8] case study has demonstrated efficacy in improving peripheral circulation [19], and frostbite can be classified into four syndromic patterns based on its clinical manifestations, with specific prescriptions applied to each pattern [7]. This suggests that herbal medicine could be effective in the treatment of frostbite.

Accordingly, the present study sought to improve the practical applicability of Korean medicine by reviewing research that has demonstrated its efficacy in the treatment of frostbite. In this study, a thorough search of both domestic and international databases identified a total of 196 articles. After excluding 45 duplicate studies, 143 articles published before the year 2000 or using inappropriate treatment methods were further excluded, leaving eight studies deemed suitable for inclusion. However, due to the inability to obtain the full text in four articles, a total of four articles were ultimately included.

In Ha et al.’s [8] case studies, all of their three patients experienced severe frostbite that required partial amputation; however, the affected region exhibited complete recovery, including the restoration of skin color, sensory function, and overall functionality through Korean medicine treatments, including acupuncture, herbal medicine, and moxibustion, without necessitating additional medical treatments. This case series is significant as it is the first study to apply traditional Korean medicine to the treatment of third-degree frostbite.

Ha et al. [8] primarily focused on direct acupuncture treatment applied to the frostbite areas, whereas Norheim and Alræk [9] selected the acupuncture points (LR3, LI4, ST36, and KI7) aimed at improving peripheral blood circulation. DIRT was also utilized to record the microvascular changes induced by acupuncture stimulation. As a result, acupuncture stimulation, as applied in this study, demonstrated beneficial effects on the dermal blood flow in a patient with residual frostbite complications. This study also highlighted the significance of thermography as a valuable and objective method for evaluating the effects of acupuncture therapy on peripheral blood circulation.

Both animal studies employed ELISA for measurement, and each study suggested the efficacy of herbal medicine and EA in the treatment of frostbite. In Kong et al.’s [10] study, EA enhanced wound healing, reduced histopathological damage to the skin tissues, and prevented the development of thrombosis in mice with a frostbite-induced injury. These effects may be mediated through the suppression of the TLR4/NF-κB signaling pathway, indicating that EA could represent a viable therapeutic approach for alleviating frostbite-induced damage.

According to Li et al. [11], frostbite-affected rats showed a compromised immune function and a propensity for thrombus formation. They indicated that HGWD may alleviate immune system dysfunction and imbalance between TXB2 and PGF1α.

A limitation of the present study is the insufficient number of selected studies, with only four articles included in the final analysis. Although Korean medicine has shown efficacy in the treatment of frostbite, there is a lack of case reports on this topic, and randomized controlled trials (RCTs) are absent. In Norheim and Alræk's [9] study, the uncertainty regarding self-resolution during the intervention period may be a limitation. It remains unclear whether the recorded changes in DIRT are attributed to the effects of acupuncture or simply a result of natural recovery.

Despite the abovementioned limitations, based on the fact that the cases and experimental studies analyzed in this paper demonstrate that Korean medicine treatment has a definite effect on frostbite management without side effects, this review is expected to encourage further clinical research and motivate many Korean medicine practitioners to apply Korean medicine for frostbite treatment in clinical practice. Although not formally presented as case reports, numerous cases of severe frostbite have been treated using Korean medicine. Patients who received this treatment for frostbite have reported high levels of satisfaction due to the excellent therapeutic outcomes. In addition, Korean medicine treatments have minimal side effects, making them a safe approach for frostbite management. In particular, because acupuncture is considered to be cost-effective, placing minimal financial burden on patients, it is anticipated that acupuncture will have high applicability for frostbite treatment in clinical practice.

To enhance the level of evidence for Korean medicine treatments for frostbite, further case reports and extensive RCTs are necessary in future studies. Finally, we suggest that Korean medicine treatments be broadly implemented and further developed to reduce the sequelae in patients with frostbite and to enhance the therapeutic outcomes.

Based on the review of four studies published from January 1, 2000, to August 15, 2024, Korean medicine treatment, including acupuncture, herbal medicine, EA, and moxibustion, could be potential treatments for frostbite. Nevertheless, additional studies with larger sample sizes are necessary to establish the effectiveness and safety of Korean medicine treatments for managing frostbite.

Conceptualization: HRK. Data curation: HRK. Formal analysis: HRK. Investigation: HRK. Methodology: HRK. Writing – original draft: HRK. Writing – review & editing: All authors.

The authors have no conflicts of interest to declare.

None.

This research did not involve any human or animal experiment.