The Efficacy of Complementary and Alternative Medicines Utilized In Cosmetic and Surgical Dermatology: A Comprehensive Review

J Clin Aesthet Dermatol. 2025;18(6):29–40.

by Promise Ufomadu, BSA; Bartley Joseph Gill, MD, PhD; Theodore Rosen, MD; Ikue Shmizu, MD; and Ida Orengo, MD

Mr. Ufomadu, Drs. Gill, Orengo, Rosen, and Shmizu are with the School of Medicine at Baylor College of Medicine in Houston, Texas. Drs. Orengo, Rosen, and Shmizu are also with the Department of Dermatology at Baylor College of Medicine in Houston, Texas. Dr. Gill is also with Memorial Hermann Health Systems in Houston, Texas.

FUNDING: No funding was provided for this article.

DISCLOSURES: The authors declare no conflicts of interest relevant to the content of this article.

Abstract: Background: Lately, there has been a growing demand for the utilization of complementary and alternative medicines (CAMs) with dermatological applications. This is true despite limited RCT-level studies on such agents. This presents a barrier for dermatologists and fellow clinicians in counseling patients who may be using or are tempted to use these CAM modalities. This review highlights CAM agents used by patients for applications in cosmetic and surgical dermatology, exploring their efficacy and toxicity profiles. Methods: A comprehensive review was conducted on the effectiveness of several CAMs utilized in cosmetic and surgical dermatology by patients. A literature search was performed using PubMed, Embase, Google Scholar, Web of Science, and Cochrane. Results: Most CAM agents studied had statistically insignificant results, and for CAM agents that had significant results in efficacy, the studies were questionable due to flawed randomization, lack of proper blinding, faulty data analysis, poor study design, suggestion of bias, small sample size, and limited clinical application. Conclusion: CAM agents have promising potential in dermatologic use; however, more RCT-level studies are needed. A study design that either emphasizes a comparison between the CAM agent and conventional therapy, or the CAM agent with or without conventional therapy should be incorporated in future studies. As of now, dermatologists should be cognizant of bias in published studies demonstrating the effectiveness of certain CAM agents, as well as the possible adverse effects. Keywords: Complementary and alternative medicine, mohs, photoaging, skin cancer, bcc, bowen, scars, Steven Johnson syndrome, melanoma, botanicals

Introduction

Complementary and alternative medicine (CAM) usage has grown substantially, peaking in 2019 at 80 percent in the United States (US) and 91 percent in Europe.¹ In surgical settings, 50 to 67 percent of outpatients report perioperative CAM use.^2,3 Specific to dermatologic surgery, 20 percent of CAM usage was reported among Mohs micrographic surgery patients.⁴ Given such a high prevalence of CAM utilization by dermatology patients, understanding CAM efficacy and potential side effects is relevant for dermatologic surgeons.

This review also explores CAM agents utilized for cosmetic dermatology applications like photoaging. “Cosmeceutical” and “nutraceutical” usage is widespread, contributing to a $4 billion cosmetic botanicals market in 2002, despite limited randomized controlled trial (RCT) data supporting manufacturer claims.^5,6 Dermatologists play an important counseling role for patients using these modalities. Additionally, this review highlights CAM agents with dermatologic side effect risks to aid diagnosis and treatment. When reasonable, the Jadad Scale will assess the quality of RCT evidence on dermatologic CAM therapies to guide practitioners on potential efficacy (Table 1).⁷ Heightened scrutiny of studies should help practitioners differentiate between scientifically proven CAM agents and those that merely claim efficacy.

Skin Cancer—Prevention and Primary Treatment

Polyphenols and green tea catechins in skin cancer prevention.The literature on CAM therapies for non-melanoma skin cancer (NMSC) and melanoma primarily focuses on polyphenols like green tea catechins’ effects on preventing precancerous events.⁸ Numerous in vitro and animal studies elucidate the proposed protective mechanisms, including anti-inflammatory (decreased COX-2, PGE, cytokines), antioxidant (decreased reactive oxygen species, increased antioxidant enzymes), and DNA repair activity (decreased pyrimidine dimers via NER), especially epigallocatechin-3-gallate (EGCG).^9–23 Human studies show similar photoprotective effects like reduced erythema and reduced markers of oxidative stress markers. However, these human studies suffer from small sample sizes, lack of vehicle controls, and potential investigator bias.^19,24–28

Other human studies have deployed proper controls to study the UV-protective effects of lotion containing green tea extract (GTE), but have also found more mixed results. Mnich et al²⁵ compared the topical application of lotion with and without 0.4% GTE in 18 subjects and found an inhibition of p53 expression and decreased keratinocyte apoptosis in GTE-treated skin. However, this study found no difference in erythema reduction or thymidine dimer formation when comparing lotions with and without GTE. It should also be noted that, while decreased p53 expression and apoptosis may be a sign of photoprotection, these same processes are also critical in halting neoplasm development, such that GTE may potentially have the opposite effect than intended. Li et al²⁸ deployed a series of lotions with a range of higher GTE concentrations (2–5%) compared to lotion-only controls and concluded that GTE-containing lotions decreased UV-induced erythema, epidermal thickness, and MMP expression. However, no statistics were offered for erythema or MMP measurements, and epidermal thickness was only modestly decreased in some GTE formulations and still substantially greater than in non-UV-treated skin. Perhaps most critically, there was no dose-response seen in any of the measurements, with efficacy found to be inexplicably higher at lower or moderate GTE concentrations and discordant between outcomes.

One critical aspect to note for both animal and human studies is that ECGC or GTE treatments were generally applied immediately before an acute UV exposure, and there has been little assessment of the extent of lingering protective effects if UV exposure occurs at a considerable length of time after application or if UV exposure is less intense, but prolonged. Examination of this more chronic photoprotective effect is essential as it would more realistically model how green tea or its constituent catechins would be used practically by patients as a CAM therapy. While promising, few rigorous RCTs examine clinical endpoints; only one RCT studied topical green tea extract (sinecatechins) for basal cell carcinoma.²⁹ More RCT-level evidence on clinical outcomes is needed before recommending catechins for skin cancer prevention.

Other polyphenols for cancer prevention. Resveratrol, a polyphenol found in high concentration in grape skin, berries, nuts, and other plant sources, has been studied at great length in vitro and in vivo as a potent antioxidant and anti-inflammatory agent with wide-ranging applications including cardiovascular disease, aging, and cancer.^30,31 Studies have shown inhibition of carcinogenesis at multiple stages in vitro and inhibition of skin cancer initiation and growth in rodent models with promising results. Nonetheless, no human studies or RCTs have been performed.³⁰ Similar effects have been shown with the polyphenol classes proanthocyanidins, silymarin, and the flavonoid genistein, respectively found primarily in grape seeds, milk thistle, and soybeans, with in vitro and animal studies reporting some effects decreasing UV-induced H2O2 and ROS production and inhibition of a variety of UV-induced pro-inflammatory mediators. However, these findings have yet to be shown in human studies in a clinically relevant way.⁸ Like green tea catechins, these other polyphenols have shown great promise in non-clinical studies and should prompt further investigation in RCT-level studies for effect on skin cancer prevention.

Escharotic agents. Escharotic or caustic agents are promoted as an alternative treatment for many skin lesions including NMSC with advocates claiming the products effectively destroy diseased skin leaving healthy skin in place.³² Bloodroot (Sanguinaria candensis) and zinc chloride have traditionally been the most commonly used substances, where topical application leads to tissue necrosis and eschar formation. Some in vitro data suggest that bloodroot may also possess additional anti-microbial, anti-inflammatory, and antioxidant activity.³³ These escharotics, in particular zinc chloride, were initially popularized by Frederic Mohs for use as an in situ fixative agent as part of Mohs surgery but were always deployed along with surgical excision, never alone. They have since been proven less useful than post-excision fixation of fresh tissue given that both methods show equivalent cure rates, but the in situ technique is more painful, destroys healthy tissue, and requires a 24-hour exposure period before excision.³²

These agents are sometimes promoted as the folk remedy “black and yellow salve” or sold online as a mixture of multiple different escharotic and non-escharotic CAM agents and are typically marketed as effective alternative cures with misleading wording and lack of appropriate disclaimers.^33,34 There are no credible controlled studies supporting the use of escharotic agents as an alternative or complementary treatment for NMSC, melanoma, or other skin neoplasms. Despite this fact, several case reports in the literature not only illustrate their persistent use by patients but also highlight the risks of their use. These risks include non-selective destruction of healthy skin, resultant severe scarring, and the high potential for cure failure and recurrence in the scarred skin or in an adjacent site requiring a much more extensive subsequent excision.³⁵ While some animal study data suggests that there may still be a useful complementary role of escharotic agents before Mohs excision of melanoma to promote immune stimulation,³⁶ no clinical studies yet exist to establish this efficacy, and dermatologists should be aware of the risks of these agents and strongly advise patients against their use as NMSC therapy.

Phytotherapeutics as NMSC and melanoma treatment. Glycoalkaloids (solasodine glycosides) initially derived from the Sodom apple plant (Solanum sodomaeum) and also found in eggplant have been shown in vitro to cause cancer cell-specific apoptosis and have been under investigation as a topical treatment for NMSC.³⁷ Early open studies of its application on keratoses and NMS, in addition to a recent case report involving Bowen’s disease, have suggested efficacy in cancer treatment.^38,39 Punjabi et al⁴⁰ performed one RCT in an attempt to confirm these observations, comparing BCC treatment with a keratolytic salicylic acid/urea cream with and without solasodine glycosides. The authors concluded effectiveness based on higher reported treatment success at eight weeks. However, there was no description of criteria for the primary endpoint of treatment success, and the treatment group suffered heavily from unexplained withdrawals, with these withdrawn patients inappropriately scored as treatment successes. Furthermore, even setting aside that roughly half of patients did not make it to the recurrence assessment at the one-year follow-up, recurrence rates were still higher than 20 percent, indicating this treatment is far from effective.

A myriad of other phytotherapeutic agents have been purported as remedies for different types of cancer that are too numerous to describe in detail. Oleander (Nerium oleander) and its constituent cardiac glycosides oleandrin, oleandrigenin, and others have demonstrated several potential anti-cancer mechanisms in vitro including inhibition of fibroblast growth factor-2 release via Na+/K+-ATPase pump inhibition,⁴¹ inhibition of NF-κβ,⁴² tumor cell cytotoxicity through increases in ROS,⁴³ and enhancement of apoptotic activity to limit tumor growth and enhance sensitivity to radiotherapy.^44,45 A commercial preparation of oleander extract (Anvirzel) is under investigation for cancer prevention and therapy and has been proven safe in a Phase I trial⁴⁶ but has yet to demonstrate efficacy in a Phase II trial or other RCT-level human study.

Other phytotherapeutics of note that have demonstrated efficacy specifically for skin cancer in animal models include berberine (isoquinoline alkaloids) derived from Goldenseal (Hydrastis canadensis) amongst other plants, sesquiterpenes in ginger (Zingiber officinale), extracts from willow trees (Salix caprea), and isoflavones from red clover (Trifolium pretense). All of these phytotherapeutics have demonstrated an inhibition of photocarcinogenesis in vivo, largely through anti-oxidant and selective apoptosis mechanisms,³³ and some have been investigated in their roles in combatting obesity and metabolism,⁴⁷ but none have thus far been tested in RCT-level human studies involving NMSC or melanoma.

CAMs in Post-Surgical Wound Treatment

Several agents have been purported as helpful in the perioperative period as wound healing agents. Arnica montana promotes wound healing via anti-inflammatory effects (sesquiterpene inhibition of NFκB).⁴⁸ However, only homeopathic arnica preparations avoid toxicity concerns like hypertension and nephrotoxicity related to higher concentrations experienced when ingested.^3,49 Pilot studies in the 1970s suggested bruising improvements with homeopathic arnica but had small samples, a lack of acceptable statistical analysis, and unclear blinding protocols.⁵⁰ A recent manufacturer-funded study claims benefits for post-operative ecchymosis but lacks proper randomization, blinding, and consistent endpoints.⁵¹ More rigorous studies show no arnica effect on bruising, pain, or swelling across various surgeries,^52–55 yielding a Jadad score of 3.6.

Other proposed CAM agents include honey (promoting a moist and decolonized environment) but Cochrane reviews found no efficacy for acute non-burn wounds.^56,57 Curcumin shows promise in vitro/animal models but has only limited human RCTs.⁵⁸ Though with limited accessible human RCT data, Broeolain shows insignificant findings while propolis shows a significant reduction of the wound’s surface area.^3,59–62 However, Vitamin C was found to improve scar strength post-surgery.⁶³ Aloe vera showed potential benefits (decreased postoperative pain and faster wound healing compared to control) post-hemorrhoidectomy but with randomization concerns.⁶⁴ Formulations of chamomile and gotu kola demonstrate re-epithelialization effects in animals but lack rigorous human studies.³ Calendula had one study that presented a faster healing time than the control, though there was no statistical significance.⁶⁵

Scar Treatment

Onion gel. Hypertrophic scars and keloids following surgery or trauma have prompted interest in CAM-based scar treatments due to limited conventional options.⁶⁶ Onion extract (Allium cepa, Mederma) has been studied for potential anti-inflammatory and collagen regulation benefits.⁶⁷ However, RCTs show mixed results with dubious methodological limitations.

Current human studies found no significant effects of onion gel on scar erythema and pruritus,⁶⁸ overall improvement and scar characteristics,⁶⁹ and scar appearance.⁷⁰ Jackson et al⁶⁸ lacked randomization/blinding, Clarke et al⁶⁹ had placebo uncertainty/baseline differences, and Chung et al⁷⁰ studied non-hypertrophic scars.

Published studies with positive findings suffer from methodological flaws: Koc et al⁷¹ found additive onion gel benefits with triamcinolone injections but lacked topical control/blinding/statistics. Ho et al⁷² reported reduced scarring post-laser tattoo removal without a proper description of blinding and methods. Draelos et al⁷³ showed intra-group scar improvement in a manufacturer-funded split-scar study lacking a critical placebo control. In a well-designed study, Chanprapaph et al⁷⁴ found modest benefits in height/symptoms in a split-scar cesarean study but lacked confirmation of adequate patient blinding. The lack of vehicle-placebo controls in many studies is a major limitation, as scar hydration affects healing. With inconsistent results and significant methodological issues like lack of blinding/randomization/controls (Jadad score 3.4), evidence for onion extract improving scar cosmesis remains inconclusive at best.

Silicone gel or sheeting. Silicone gel sheets/ointments (over 60 polydimethylsiloxane products) are widely used for scar prevention/treatment, though the mechanism is unclear, potentially modifying evaporative water loss and fibroblast collagen deposition rather than a chemical effect.^67,75–78 A 2008 Cochrane review of 15 RCTs found silicone sheets did not prevent overall scar development compared to no treatment, but reduced hypertrophic scarring in high-risk patients (95% CI 0.21-0.98).⁷⁸ For scar treatment, silicone sheets reduced thickness but not size, appearance, pain, or itch compared to controls. Results were mixed for color/elasticity, with no benefit over non-silicone dressings or lasers, and inferiority to triamcinolone injections for keloids.⁷⁸ Subsequent studies had issues too: inadequate masking/controls,⁷⁹ unclear randomization/outcome assessment,⁸⁰ and manufacturer affiliation.⁸¹ The lack of benefit over non-silicone dressings suggests the occlusive effect, not silicone itself, may drive positive outcomes.^78,81–83 Despite inconclusive overall efficacy and design limitations (average Jadad 3), silicone remains recommended for hypertrophic scar management, with stronger evidence in high-risk patients for reducing scar thickness.^75,84

Vitamin E. Topical vitamin E (tocopherol) has been suggested to treat scarring, with proposed anti-oxidant mechanisms, acting to reduce the formation of ROS and spread of peroxidation of cellular membrane lipids that impede healing and potentially altering the production of collagen and glycosaminoglycans.⁷⁵ A few RCTs have been performed investigating these effects. Jenkins et al⁸⁵ followed patients who underwent reconstructive graft surgery for burns for one year receiving treatment with topical triamcinolone diacetate (Aristocort), topical Vitamin E or carrier cream finding no difference in range of motion, scar thickness, graft size change, and overall cosmetic appearance between groups with outcomes helpfully grouped by burn location (hands, axillary, neck). With the caveat that outcome assessment methods were not thoroughly described, this study was large and well-designed with outcomes measured out to one year. Adverse reactions consisting of mild itching and maculopapular eruptions occurred slightly more frequently in the two treatment groups compared to control. Palmieri et al⁸⁶ tested the complementary application of topical E to silicone plates to treat established scars for two months and concluded enhanced efficacy over the silicone alone based on data showing a higher percentage of patients with a greater than 50 percent improvement on a subjective scar scale. Little weight should be placed on this study, however, as no randomization was described, no placebo control gel was used, no blinding was described, and no numerical data with standard deviations of the scoring was reported. In a different small RCT, Baumann et al⁸⁷ examined post-Mohs scarring in a split-scar treatment design, comparing an ointment with and without added Vitamin E. The authors found no improvement in blinded subjective assessment of cosmesis but did note a substantial percentage of contact dermatitis reactions on the Vitamin E sites. The methodology of this study is seriously flawed, however, as scar sides were inappropriately randomized (patient-chosen), no information was provided on outcome measurements of improvement, and no statistics were provided. Furthermore, the formulation and concentration of Vitamin E applied, taken from caplets intended for oral use, is known to cause contact reactions, with other formulations that are more typically topically applied and do not readily cause contact dermatitis not tested. In a larger study, Zampieri et al⁸⁸ compared topical application of a commercial Vitamin E gel or petrolatum control for 15 days before and 30 days after inguinal incision surgery in children with authors concluding improved efficacy of the Vitamin E treatment based on minor, but significant differences in keloid formation and subjective cosmesis. There was no mention of the method of randomization in this study or description of baseline characteristics for comparison between groups, and investigators were not blinded. Furthermore, the control topical may have not been well-matched (was not a treatment gel vehicle), and the primary outcome relied on parental (subjective) evaluation and classification of the degree of scar cosmesis and keloid formation, clinical descriptors that would have been more appropriately evaluated by an investigating physician. Khoo et al⁸⁹ recently performed a large (n=122), well-designed study comparing the treatment of new (<2 weeks) surgical scars with 5% Vitamin E cream or a well-matched placebo and found no inter-group differences throughout the 16-week study in blinded patient and investigator scoring, visual analog scale scoring of photographs by independent investigators or live Doppler imaging of blood flow. While no intention-to-treat analysis was performed, drop-out rates were almost identical between groups. Further of note, the authors did not record any adverse events related to contact dermatitis. Overall, the average Jadad score for the quality of evidence that Vitamin E promotes scar treatment or prevention is 3 for reasons already mentioned.

Photoaging. Patient demand for photoaging CAM products generated over $2 billion in sales in 2000, driving research on potential therapies.⁹⁰ Polyphenols like green tea catechins have been widely studied due to proposed anti-inflammatory and antioxidant mechanisms (anti-aging effects). However, few rigorous RCTs show clinical efficacy. In one well-designed study, Chiu et al⁹¹ compared patients using a combined 10% topical and 300mg oral GTE supplements to placebo. Investigators found no improvement after eight weeks in several patient and physician-assessed subjective photoaging-related skin characteristics (wrinkling, pigmentation) and no difference in several histologic parameters (epidermal thickness, collagen content), but did find an interesting significant difference in skin elastin content. Hsu et al⁹² conducted a left-right trial with a commercial green tea cream that also contained, amongst several other botanical agents, extracts from mangosteen (Garcinia mangostana, constituent anti-oxidant xanthones) and pomegranate (constituent polyphenols). Study authors concluded positive efficacy compared to placebo based on subjective patient preference evaluations and trending differences in computer image-analyzed periorbital skin topography characteristics. However, the results were not net positive, which contradicts this conclusion, as topography improvement was not significant, and blinded physician-assessed wrinkle grades showed no difference. Furthermore, this study featured significant methodological issues as, in addition to potential bias related to funding from the treatment cream manufacturer, the cream contained some potential botanical effectors and no information was provided to show placebo equivalence in appearance, feel, or smell to ensure proper patient blinding. Finally, Janjua et al⁹³ conducted a well-designed, prolonged two-year study comparing oral green tea supplements to placebo with evaluations including blinded physicians’ assessment of solar damage, erythema, and telangiectasias at multiple time points and study-endpoint histological characteristics. While the green tea group showed significant improvements at a few study time points, the authors ultimately concluded it was ineffective as these improvements were not sustained throughout the study or at the two-year endpoint. Given that most studies find no improvement in clinically evident measures of photoaging with green tea supplements and the major methodological problems of the few studies that do show improvement (risk of bias, publication bias, improper blinding details), the assigned averaged Jadad score for green tea supplements protection against photoaging is three.

Other agents studied with inconclusive findings include soy isoflavones,⁹⁴ black soybean anthocyanins,^95,96 resveratrol, grape seed proanthocyanidins, and genistein.⁹⁷ Though Witch hazel has promising in vitro findings,^98,99 human studies have thus far been restricted to non-RCT level studies examining reduction in UV-induced erythema following immediate application of Hamamelis-containing lotion with investigators finding slight efficacy in chromometric erythema reduction, significantly improved over matched controls only in a few of the tested vehicles and UV exposure conditions.^100,101

Ginseng (Panax ginseng) and its constituent ginsenosides or saponins have wide-ranging anti-inflammatory, antioxidant, and immunomodulatory effects in vitro.¹⁰² Cho et al¹⁰³ tested the effects of an oral preparation of red ginseng extract combined with extract from two other herbs, Torilus fructus and Corni fructus in a six-month trial. The authors concluded efficacy over placebo based on greater improvements from baseline in the treatment group in a few viscometer-measured wrinkle parameters and an improvement over baseline in content of procollagen I and fibrillin-1 fiber length derived from biopsies. However, inter-group comparisons were not made and the other endpoints tested (most wrinkle parameters and elasticity, for example) showed no change from the intra-group baseline, leaving conclusions suspect.

Other RCTs on peony root,¹⁰⁴ cork extract,¹⁰⁵ and milk thistle, gotu kola,¹⁰⁶ and almonds¹⁰⁷ had significant methodological limitations, jeopardizing study findings. While many other CAM agents exhibit significant anti-inflammatory and antioxidant mechanisms for anti-aging effects in vitro and animal studies,^108–122 rigorous human RCT evidence remains limited.

Cutaneous side effects of dermatologic CAM

Though most side effects assessed from mentioned RCTs and other studies in this review are already noted, here we present side effect profiles on specific CAM agents, more generally for dermatologic surgery. These agents could provide some reason for concern during use in the perioperative period, especially those that influence clotting and coagulation through effects on platelets or interactions with warfarin. These CAMs, their possible effect on perioperative interest, and a general mechanism are summarized in Table 4.^3,123,124 In general, information on the effect of these CAM agents on clotting or coagulation comes from in vitro or animal studies and isolated case reports, not RCTs. Thus, it is difficult for the physician to make recommendations regarding these CAMs as there is limited supporting information regarding direct mechanistic causality, dosage, concomitant confounding lifestyle or disease factors, or any other identified characteristics of patients that may be at risk for coagulation-related events if they use these agents.

Conclusion

The prevalence of CAMs in dermatology reflects consumer demand for integrative medicine approaches. While some studies suggest a promising efficacy of CAMs, significant design flaws, and methodological issues, such as improper blinding, small sample sizes, and subjective measures, undermine the credibility of these findings. Authors have tended to present results in a way that overstates CAM efficacy. Nonetheless, these studies provide a foundation for further rigorous investigation through well-designed RCTs comparing CAMs to conventional therapies. Until such trials are conducted, dermatologists should critically evaluate published CAM studies for bias and potential adverse effects. By doing so, clinicians can responsibly guide patients interested in exploring CAM products while optimizing overall outcomes.

Supplemental Figures

References

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