INTRODUCTION
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.
DISCUSSION
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
