Clinical Review

The Ketogenic Diet and Dermatology: A Primer on Current Literature

Author and Disclosure Information

The ketogenic diet has been therapeutically employed from antiquity and is still utilized today in many disease states. With the boom of the complementary and alternative health movement over the last 2 decades, the lay population has grown more interested in disease prevention and treatment via dietary and lifestyle changes and enhancing health and human performance. The ketogenic diet, whether exclusive or intermittent, has been purported by health care professionals and laypersons alike to meet these demands. In this review article, we look to the current literature for proven and possible mechanisms by which ketones and a ketogenic diet may be utilized in the field of dermatology and direct our readers to pursue further research for this promising potential treatment option.

Practice Points

  • The ketogenic diet has been employed since antiquity for varying ailments and has a good safety and efficacy profile if administered by a knowledgeable provider.
  • New literature is showing promising potential roles for the ketogenic diet as an adjunctive therapy, particularly in the realm of inflammatory disorders, metabolic diseases, and malignancy.
  • The dermatologist should be aware of this diet because it is gaining popularity with physicians and patients alike. Dermatologists also should know how it can potentially benefit a number of patients with dermatologic diseases based on small clinical trials, population studies, and basic science research.


 

References

The ketogenic diet has been therapeutically employed by physicians since the times of Hippocrates, primarily for its effect on the nervous system.1 The neurologic literature is inundated with the uses of this medicinal diet for applications in the treatment of epilepsy, neurodegenerative disease, malignancy, and enzyme deficiencies, among others.2 In recent years, physicians and scientists have moved to study the application of a ketogenic diet in the realms of cardiovascular disease,3 autoimmune disease,4 management of diabetes mellitus (DM) and obesity,3,5 and enhancement of sports and combat performance,6 all with promising results. Increased interest in alternative therapies among the lay population and the efficacy purported by many adherents has spurred intrigue by health care professionals. Over the last decade, there has seen a boom in so-called holistic approaches to health; included are the Paleo Diet, Primal Blueprint Diet, Bulletproof Diet, and the ketogenic/low-carbohydrate, high-fat diet. The benefits of ketones in these diets—through intermittent fasting or cyclical ketosis—–for cognitive enhancement, overall well-being, amelioration of chronic disease states, and increased health span have been promulgated to the lay population. But to date, there is a large gap in the literature on the applications of ketones as well as the ketogenic diet in dermatology and skin health and disease.

The aim of this article is not to summarize the uses of ketones and the ketogenic diet in dermatologic applications (because, unfortunately, those studies have not been undertaken) but to provide evidence from all available literature to support the need for targeted research and to encourage dermatologists to investigate ketones and their role in treating skin disease, primarily in an adjunctive manner. In doing so, a clearly medicinal diet may gain a foothold in the disease-treatment repertoire and among health-promoting agents of the dermatologist. Given the amount of capital being spent on health care, there is an ever-increasing need for low-cost, safe, and tolerable treatments that can be used for multiple disease processes and to promote health. We believe the ketogenic diet is such an adjunctive therapeutic option, as it has clearly been proven to be tolerable, safe, and efficacious for many people over the last millennia.

We conducted a PubMed search of articles indexed for MEDLINE using varying combinations of the terms ketones, ketogenic, skin, inflammation, metabolic, oxidation, dermatology, and dermatologic and found 12 articles. Herein, we summarize the relevant articles and the works cited by those articles.

Adverse Effects of the Ketogenic Diet

As with all medical therapies, the ketogenic diet is not without risk of adverse effects, which should be communicated at the outset of this article and with patients in the clinic. The only known absolute contraindications to a ketogenic diet are porphyria and pyruvate carboxylase deficiency secondary to underlying metabolic derangements.7 Certain metabolic cytopathies and carnitine deficiency are relative contraindications, and patients with these conditions should be cautiously placed on this diet and closely monitored. Dehydration, acidosis, lethargy, hypoglycemia, dyslipidemia, electrolyte imbalances, prurigo pigmentosa, and gastrointestinal distress may be an acute issue, but these effects are transient and can be managed. Chronic adverse effects are nephrolithiasis (there are recommended screening procedures for those at risk and prophylactic therapies, which is beyond the scope of this article) and weight loss.7

NLRP3 Inflammasome Suppression

Youm et al8 reported their findings in Nature Medicine that β-hydroxybutyrate, a ketone body that naturally circulates in the human body, specifically suppresses activity of the NLRP3 inflammasome. The NLRP3 inflammasome serves as the activating platform for IL-1β.8 Aberrant and elevated IL-1β levels cause or are associated with a number of dermatologic diseases—namely, the autoinflammatory syndromes (familial cold autoinflammatory syndrome, Muckle-Wells syndrome, neonatal-onset multisystemic disease/chronic infantile neurological cutaneous articular syndrome), hyperimmunoglobulinemia D with periodic fever syndrome, tumor necrosis factor–receptor associated periodic syndrome, juvenile idiopathic arthritis, relapsing polychondritis, Schnitzler syndrome, Sweet syndrome, Behçet disease, gout, sunburn and contact hypersensitivity, hidradenitis suppurativa, and metastatic melanoma.7 Clearly, the ketogenic diet may be employed in a therapeutic manner (though to what degree, we need further study) for these dermatologic conditions based on the interaction with the NRLP3 inflammasome and IL-1β.

Acne

A link between acne and diet has long been suspected, but a lack of well-controlled studies has caused only speculation to remain. Recent literature suggests that the effects of insulin may be a notable driver of acne through effects on sex hormones and subsequent effects on sebum production and inflammation. Cordain et al9 discuss the mechanism by which insulin can worsen acne in a valuable article, which Paoli et al10 later corroborated. Essentially, insulin propagates acne by 2 known mechanisms. First, an increase in serum insulin causes a rise in insulinlike growth factor 1 levels and a decrease in insulinlike growth factor binding protein 3 levels, which directly influences keratinocyte proliferation and reduces retinoic acid receptor/retinoid X receptor activity in the skin, causing hyperkeratinization and concomitant abnormal desquamation of the follicular epithelium.9,10 Second, this increase in insulinlike growth factor 1 and insulin causes a decrease in sex hormone–binding globulin and leads to increased androgen production and circulation in the skin, which causes an increase in sebum production. These factors combined with skin that is colonized with Cutibacterium acnes lead to an inflammatory response and the disease known as acne vulgaris.9,10 A ketogenic diet could help ameliorate acne because it results in very little insulin secretion, unlike the typical Western diet, which causes frequent large spikes in insulin levels. Furthermore, the anti-inflammatory effects of ketones would benefit the inflammatory nature of this disease.

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