Clinical Benefits of Circadian-based Antioxidant Protection and Repair

December 2020 | Volume 19 | Issue 12 | Original Article | 1209 | Copyright © December 2020


Published online November 30, 2020

Zoe Diana Draelos a, Elizabeth T Makino b, Kuniko Kadoya b, Audrey Nguyen b, Lily I Jiang c, Rahul C Mehta b

aDermatology Consulting Services, PLLC, High Point, NC
bAllergan Aesthetics, an AbbVie Company, Irvine, CA
cThomas J. Stephens & Associates, Inc., Richardson, TX

Abstract
Skin activities follow endogenous circadian rhythms resulting in differences between daytime and nighttime properties. To address the variations in skin needs, a novel circadian-based dual serum system (LVS) was developed. A 12-week, double-blind, randomized, regimen-controlled, multi-center study was conducted to assess the efficacy and tolerability of LVS on subjects presenting with moderate-severe photodamage. 61 Female subjects (36–65 years; Fitzpatrick skin types I–VI) completed the study. The active group received LVS (daytime serum and nighttime serum) and basic skin care regimen (moisturizer and SPF 35 sunscreen), while the control group received the basic skin care regimen only. In addition to clinical grading, subject self-assessment questionnaires, and standardized photography, punch biopsies were taken in a subset of subjects for immunohistochemistry. Additionally, swab samples were taken for skin surface oxidation analysis. Significant improvements over control were observed in the active group in Radiance (weeks 4, 8, and 12), Overall Photodamage, Tactile Toughness, and Global Fine Lines/Wrinkles (week 12). Biopsy results, skin swab analysis and standardized photographs support the clinical grading findings. At all follow-up visits, LVS was consistently highly rated over control by subjects, with a significant proportion of subjects agreeing at week 12 that LVS “improved the radiance of my skin,” and “improved the overall health and look of my skin”. Results from this study suggest that LVS may provide essential protective and reparative effects to skin exposed to the damaging effects of environmental factors, and also demonstrates the value of including skin circadian rhythm-based concepts in a topical skincare regimen.

J Drugs Dermatol. 2020;19(12):1209-1214. doi:10.36849/JDD.2020.5355

INTRODUCTION

The concept of human body rhythms has been popularized as important in overall body health. These rhythms are characterized as fluctuations in mental, physical, and emotional well-being based on the clock.1 These fluctuations are related to the day/night cycle, hormones, meals, sleep/wake cycle, adrenal gland production, thyroid gland, and clock genes. The study of the body circadian rhythm is known as chronobiology with studies of the body's inner clock dating back to the 18th century. There are three types of chronobiology rhythms: infradian rhythms, ultraradian rhythms, and circadian rhythms. Infradian rhythms last more than 24 hours and are repeated only every few days, weeks, or months representing such activities as female menses. Ultradian rhythms are shorter than 24 hours and often last several hours, such as ingestion of food. Finally, circadian rhythms last 24 hours with distinctive day/night cycles.2

Circadian rhythms are endogenous and adjusted to the local environment by cues call zeitgebers, meaning "time giver" in German. The 2017 Nobel prize in physiology or medicine was awarded for research in molecular mechanisms controlling circadian rhythms in fruit flies. In humans, the circadian clock is in the suprachiasmatic nucleus, located in the hypothalamus. Information is transmitted to the suprachiasmatic nucleus via the retina that contains specialized photosensitive ganglion cells. PER1 and PER2 genes are expressed in the suprachiasmatic nucleus representing the primary circadian pacemaker in the human brain. These circadian rhythms are also important in the skin with robust autonomic clocks in keratinocytes, fibroblasts, melanocytes, mast cells, and hair follicles.3 Important skin functions affected by circadian rhythms include free radical production and neutralization, DNA damage and repair, keratinocyte/fibroblast differentiation and proliferation, and barrier and immune functioning.4 Direct and indirect antioxidant protection play an important role in supporting these circadian rhythm skin functions.

There are key differences between skin activities that occur during the day and night.14 During the day, the skin has the highest pH, sebum production, and thickness with the lowest