Acne Vulgaris: The Role of Oxidative Stress and the Potential Therapeutic Value of Local and Systemic Antioxidants

June 2012 | Volume 11 | Issue 6 | Original Article | 742 | Copyright © June 2012

Acne vulgaris is a common dermatological condition characterized by hormonally-mediated sebum overproduction, follicular hyperkeratinization, and chronic inflammation of the pilosebaceous unit. Microbes, genetic susceptibilities, and various environmental factors have been linked to the pathogenesis of the condition. Over the last several years it has become apparent that patients with acne are under increased cutaneous and systemic oxidative stress. Moreover, the burden of oxidative stress may not be a mere consequence of acne; rather, the oxidative stress, lipid peroxidation in particular, may be an early event that helps to drive the acne process. Here, we explore the role of oxidative stress and review the preliminary research involving the administration of local and systemic antioxidants.

J Drugs Dermatol. 2012;11(6):742-746


Acne vulgaris is a common disease that has increased in frequency in the last half century, particularly among adult women in developed nations.1 The disease is characterized by sebum overproduction, follicular hyper-keratinization, and an increased release of inflammatory-mediating chemicals. The experience of acne can include significant psychological disability such as clinical depression, anxiety, and suicide.2 Despite numerous advances in technology and experimental dermatology, the complete pathological process and sequence of events in acne remains unclear.
Historically, it was believed that follicular plugging (comedones) preceded Propionibacterium acnes colonization, with inflammation in the form of papules and pustules following suit. Recent discoveries indicate, however, that inflammation and oxidative stress might play an early role in initiating the pathogenesis of acne, countering conventional thoughts on the sequence of events in acne pathogenesis. For example, it has been shown that subclinical inflammatory events actually precede hyperproliferative and abnormal differentiation events in acne-prone skin.3,4 It is intriguing, but still unclear, why proinflammatory markers such as interleukin-1 (IL-1) are elevated around clinically normal pilosebaceous follicles in acne patients. The generation of reactive oxygen species (ROS) may be an important driver of early inflammatory events.
Free radicals, molecules with unpaired electrons in their outer orbit, are continuously formed endogenously during the normal metabolic processes. Since free radicals are highly reactive species, capable of damaging biomolecules and cellular structures (lipids, proteins, DNA) in the skin and elsewhere, humans have evolved with an efficient antioxidant defense system to minimize potential for damage. This defense system is directly supported by raw materials derived from dietary sources, including antioxidant nutrients (eg, vitamins C and E) and non-nutritive phytochemicals (eg, polyphenols). The intricate antioxidant enzyme system within the skin is operated with the assistance of co-factor nutrients such as selenium and zinc. As we will discuss in more detail, research has shown that in acne the normal antioxidant defense system operations appear to be overwhelmed. The 50-year-old lipid peroxidation theory of acne delineates a possible mechanism for the initial release of inflammatory mediators in the acne process. As sebum components such as squalene are oxidized, irritating free radicals are released into the tissues. Coupled with the enhanced comedogenicity of these oxidized products, free radicals and peroxides might initiate and maintain the damaging inflammatory pathway in acne.5-7 Based on this theory, the administration of oral and locally-delivered antioxidants might serve to protect against the initiating factor triggering the acne process, lipid peroxidation.


Systemic Indicators of Oxidative Stress Burden

Before examining the research related to local cutaneous oxidative stress in acne, a review of blood markers serves to highlight just how significant the burden of oxidative stress may be in those with acne. These studies provide indirect, yet very obvious indicators of a mismatch between an oxidative stress burden and a diminished antioxidant defense system capacity in acne. Blood antioxidant enzyme activities, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), are lower in patients with papulopustular acne as compared to controls.8 It appears as though these antioxidant enzymes might be depleted at a faster rate in those who suffer from the chronic inflammation that characterizes acne. Decreased antioxidant levels are coupled