Broadening Definitions: What Constitutes a Natural or Organic Treatment?

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Patients often prefer or request natural therapies from physicians. This may be partly due to the perception that these will better agree with their body or a tendency to accept pseudo-profound information.^1-3 Natural treatments may be viewed by patients as safer than prescription medications, which are often considered chemical, unnatural, and foreign, traits that patients believe will increase the risk of adverse effects. Although patients might acknowledge conventional treatments as more efficacious, they may accept the lower efficacy of treatments considered natural due to a perception of greater safety.¹ 

In dermatology, corticosteroids are a cornerstone of treatment for a wide range of conditions. Patients often hesitate to use steroids due to fear of adverse effects, resulting in poor treatment outcomes. The fear may be due in part to conflating corticosteroids with anabolic steroids.¹ However, corticosteroids are produced by living organisms—humans, animals, and even plants— and could be considered “natural.” 

The fact that many patients are interested in receiving natural treatments for their skin disease has been recognized.^2,3 The use of plant extracts for the treatment of various skin conditions commonly seen by dermatologists has also been described.^4,5 Given some patients’ preference for natural treatments, we have compiled a nonexhaustive list of commonly used treatments in dermatology that, at least arguably, fit into the class of natural treatments. 

Methods 

Regarding medications, there is no standard definition of natural. Although there is a definition of organic produce according to the US Department of Agriculture, the label “organic” or “natural” does not extend to medicines as far as federal regulations are concerned. We are building on the definition of natural products as coming from or being made in living cells, as well as those derived from substances produced by human, plant, or animal cells.^6,7 We searched through medical journals, books, and nonmedical sources for treatments used in dermatology that fit these criteria. We classified the treatments as traditional natural products, minerals, vitamins and vitamin analogs, corticosteroids, and biologics. 

Results 
Traditional natural products 

These are what most people think of first when the term natural comes up. Often, these are classified as complementary and alternative medicine (CAM) therapies. Each product has its own benefits, although many lack the strong, quality scientific evidence of efficacy that comes from clinical trials. There is also a lack of regulation and oversight by the US Food and Drug Administration (FDA), and patients and providers alike must be wary of active ingredients, possible contamination, and interactions with other drugs.⁸ 

Petroleum comes from hydrocarbons formed by natural decomposition of plants and animals, and petroleum jelly is adherent and insoluble in water. Petroleum jelly is used as a moisturizer and for wound healing. Coconut oil, extracted from the meat of coconuts, has a high concentration of saturated fats and is also a commonly used moisturizer. Similar to coconut oil are avocado oil, olive oil, and shea butter. Aloe vera is among the more popular and well-known natural alternatives to conventional medicines. It can be used as a skin softener and moisturizer, analgesic, and for wound healing.^8,9 Its efficacy in treating psoriasis via anthraquinones in the plant’s leaves has been proposed but has not been established.¹⁰ Fumarates from the fumitory plant and cayenne pepper extracts have also been used to treat psoriasis.¹¹ Other CAM analgesics and anti-inflammatory agents include arnica flower, calendula flower, comfrey, chamomile, capsaicin, plantain leaves, oats, St. John’s wort, and tea tree oil. Witch hazel causes vasoconstriction in swollen tissue, which has a soothing effect and reduces swelling.¹¹ Chickweed has anti-inflammatory properties and can be used in eczema as a step-down treatment from cortisone cream.¹¹ 

Another area where CAM therapies are used in dermatology is in the treatment of hyperpigmentation.¹² Ellagic acid from strawberries, cherries, and pomegranates inhibits melanin synthesis, whereas lignin peroxidase and kojic acid found in fungi break down melanin. Soy and niacinamide inhibit melanosome transfer into the epidermis, thus preventing skin darkening.¹³ Soy inhibits the formation of skin cancers in mice through the inhibition of lipid peroxidation and chemical and ultraviolet light B (UVB)-induced carcinogenesis by its estrogen-like component genistein.¹⁴ Topical green tea is a photoprotective complement to sunscreen, and also has epigallocatechin gallate and caffeine, which decrease the number of nonmalignant and malignant skin tumors in SKH-1 hairless mice pretreated with UVB.¹⁵ 

Wound healing is yet another area in dermatology where CAM therapies are used.⁸ Aloe vera, mentioned previously, enhances cell proliferation, cell migration, and vascular epidermal growth factor secretion and helps prevent cell senescence. This is thought to be linked to activation of the MAPK/ERK signaling pathways.¹⁶ Cocoa butter improves re-epithelialization of second-degree burn wounds.¹¹ Honey has antimicrobial effects, retains moisture in wounds, and promotes angiogenesis to aid the wound healing process.¹¹ Beta-glucan, a component of the cell wall in bacteria, fungi, and plants, enhances the cellular response to injury by stimulating leukocytes.¹¹ Berberine from bearberry and goldenseal has antibiotic properties. So do tea tree oil and oregano oil, but they have a risk of causing allergic contact dermatitis and need to be diluted before use.¹¹ 

Minerals 

These are chemical elements that play a role in metabolism. Essential minerals are those which the body cannot produce and must be obtained via the diet. Use of minerals in the dermatology setting is not regulated by the FDA. 

Zinc is used for protection from solar radiation. It is an essential mineral, and deficiency often manifests in the skin. Copper and zinc are both used for anti-aging purposes.¹¹ Selenium inhibits tyrosinase at the cutaneous level.¹⁷ Silica supports the connective tissue matrix, but excess supplementation can have detrimental side effects.¹⁷ Topical strontium may be used to reduce pruritus.¹⁷ 

Prescription medications 

These include vitamin analogs, corticosteroids, and biologics. Despite requiring prescriptions, they are derived from natural sources. These prescription medications have been studied extensively and are regulated by the FDA. 

Vitamins are commonly used as treatments in dermatology. Vitamin A analogs (retinoids) are produced by our body and bind to and activate retinoic acid receptors through direct ligand-receptor binding, eliciting transcription of retinoic acid-responsive genes and resulting in normalization of abnormal skin desquamation.¹⁸ They are used in dermatology to treat acne, rosacea, and psoriasis, among other diseases. Vitamin C is involved in the synthesis of collagen and elastin—2 main components of the skin’s architecture—and has antioxidant and anti-inflammatory properties. It is also used to treat patients with photoaging and hyperpigmentation.¹⁹ Vitamin D is produced by the human body through a multi-step process. Various forms of vitamin D have been used in the treatment of psoriasis. 

Corticosteroids are critical products of the human adrenal glands, which serve to maintain homeostasis in the body and modify the functions of epidermal and dermal cells and leukocytes participating in proliferative and inflammatory skin diseases.²⁰ Several more potent corticosteroids have been developed synthetically, but they act on the same steroid receptors in our body, often to reduce the inflammatory component of diseases. While most steroids manufactured today are created via extensive chemical reactions, there are several ways of synthesizing and collecting various steroid compounds using fermentation methods in yeasts.²¹ Salvestrols, a popular natural treatment, are compounds made by plants as a response to physiologic stressors, such as infection, predators, and UV light. They are analogous to the human steroid hormones, even having the same “-sterol” moniker. 

Biologics are antibody or protein products used to treat diseases via immune modulation. Antibodies and proteins are produced by living cells in both humans and other living organisms and serve a multitude of purposes. Biologics are complex glycoproteins manufactured in living cells and could be considered natural by definition. Etanercept is a fusion protein combining the tumor necrosis factor-alpha (TNF-α) receptor to the constant end of the IgG-1 antibody.²² Adalimumab is a human monoclonal antibody that binds to TNF- α.²² Infliximab is a chimeric antibody that binds to TNF-α and is composed of mouse and human DNA.²² Secukinumab is a human monoclonal antibody that binds to IL-17.²² Ustekinumab is a human monoclonal antibody that binds to IL-12 and IL-23.²² Other relevant biologics include ixekizumab, brodalumab, guselkumab, risankizumab, tildrakizumab, and bimekizumab (Table). All these biologics work to decrease immune activation in various ways, leading to decreased reactivity in hypersensitivity and autoimmune conditions. 

Discussion 

The internet has provided a plethora of information and advice regarding CAM therapies, commonly labelled as “natural” or “holistic.” Although some information comes from reputable sources, other information may misrepresent the efficacy of these treatments and might even result in health problems.⁸ The repeated use of herbs, like with conventional medicines, can lead to development of allergies.¹¹ In addition, certain products and supplements interact with other drugs and may alter drug metabolism to the point where drug concentrations are either too low to be effective or too high and cause toxicity. 

Many other drugs not listed here are organic chemicals. These include psoriasis treatments, such as deucravacitinib and apremilast, and atopic dermatitis treatments, such as upadacitinib and abrocitinib. The list of nonorganic medications used in dermatology is much smaller than the organic list and includes super-saturated potassium iodide and aluminum chloride hexahydrate, inorganic chemicals that are clearly not organic. 

Conclusion 

Often, challenges can be turned into opportunities. The aim of this review is to describe the broad list of dermatologic products that can be, at least arguably, considered natural or organic treatment options. This is an extremely relevant topic, as patients are more educated about their health care than ever and continue to request “safer” alternatives to some of the commonly used medications in dermatology. Using the broadened definition, over 50 commonly used medications in dermatology have been specified, which may be helpful to patients who desire a holistic approach to care yet need potent medications to control their skin disease and increase quality of life. By sharing this broadened definition of “natural” and explaining it to patients, they may feel more at ease with treatment recommendations and better adhere to their treatment plan. Working together with the patient, dermatologists can use this list to help select an appropriate treatment for several common conditions. 

References
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Dr Melton is a resident at the University of Kentucky College of Medicine in Lexington, KY. Dr Feldman is a professor of dermatology, pathology, social sciences and health policy, and molecular medicine and translational science at Wake Forest University School of Medicine in Winston-Salem, NC, and the chief medical editor of The Dermatologist. Dr Taylor is an associate professor of dermatology at Wake Forest University School of Medicine. Dr Soker is a resident at Cambridge Health Alliance in Cambridge, MA. 

Disclosure: Dr Feldman has received research, speaking, and/or consulting support from Eli Lilly and Company, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen, Dermavant, Arcutis, Novartis, UCB, Helsinn, Sun Pharma, Almirall, Galderma, Leo Pharma, Mylan, Ortho Dermatology, Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, Ono, Micreos, Incyte Corporation, Perfect Corp, Target-Derm, Verrica Pharmaceuticals, and Voluntis. He is founder and part owner of Causa Research and holds stock in Sensal Health.