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Uncovering a cosmetic ingredient that improves well-being and sleep quality by preserving the natural cycle of melatonin

By Morgane De Tollenaere, Emilie Chapuis, Amandine Scandolera and Romain Reynaud, Givaudan Active Beauty

Written by Morgane De Tollenaere, Emilie Chapuis, Amandine Scandolera and Romain Reynaud
EURO COSMETICS Magazine • Uncovering a cosmetic ingredient that improves well-being and sleep quality by preserving the natural cycle of melatonin • Morgane De Tollenaere, Emilie Chapuis, Amandine Scandolera and Romain Reynaud • Morgane De Tollenaere, Emilie Chapuis, Amandine Scandolera and Romain Reynaud
November / December 2023
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Abstract
The skin is a powerful somatosensory system with numerous sensory nerve endings and shares a common embryogenic origin with the neuronal system. Melatonin, a molecule that regulates sleep and possesses anti-ageing and antioxidant properties, is expressed in both the brain and skin. Blue light exposure from digital devices disturbs the melatonin cycle, negatively affecting sleep quality and skin integrity. In a recently published paper (De Tollenaere et al., 2023), we demonstrated that the melatonin cycle was preserved in a coculture of sensory neurons and keratinocytes, and that our Synchronight™contains compounds that bind to the melatonin receptor, resulting in a significant reduction of wrinkles, evidenced in volunteers. On this basis and according to the literature, we hypothesised that Synchronight™ may have protected the sleep quality of volunteers by protecting the melatonin cycle at the skin level. Consequently,
we conducted a clinical study in which volunteers were exposed to blue light before bedtime, finding that the extract reduced the number of awakenings and improved sleep quality in volunteers, demonstrating a well-being effect.

Digital stress can disturb sleep quality, impacting well-being and health

The skin is the largest sensory organ of the human body, being innervated with a large number of intra-epidermal sensory nerve endings. It is a powerful somatosensory system that can detect
environmental stimuli. This is explained by the fact that skin and neuronal systems share a common embryogenic origin: the neuroectoderm1.
Numerous molecules are expressed by both the brain and skin, showing that well-being is linked to the skin and that cosmetic products have the potential to modulate it thanks to this par-ticular connection 1, 2.
The term “neurocosmetics” appeared in the 2000s after several studies demonstrated that stress, social interactions, pleasure, relaxation and sleeping mediated by cortisol, beta-endorphins, dopamine, serotonin, oxytocin, melatonin… could trigger various biological functions in the skin, such as soothing, anti-ageing and antioxidant activity 1, 2.

Inversely, skin disease may negatively impact mood and reduce self-confidence 3, 4. These studies illustrate the powerful link between skin and the brain, and the possible positive or negative interactions.
For our study, we were interested in melatonin in particular. Melatonin is a powerful hormone released by the pineal gland, well-known for its sleep-regulating properties 4 – 6. Production of
melatonin is rhyth-med; it increases during the night, controlling the falling asleep phase, and its level is at its lowest during the day. An undisturbed cycle equates to good sleep quality, which
correlates to good brain performance, health and well-being.
The other biological benefits of melatonin, especially to the skin, are less known outside the scientific community. For a start, melatonin is a powerful anti-ageing molecule thanks to its antioxidant property 7– 9. Indeed, melatonin receptors (MT1R) are expressed in various skin cells, such as keratinocytes and fibroblasts (among others), and allow biological modulation of gene expression 10 – 14. Melatonin is also able to cross the lipid bilayers thanks to its amphiphilic property and act directly in the cytoplasm, such as free radicals scavenging activity (reactive oxygen species (ROS) and nitric oxide (NO)) and calcium homeo-stasis 14, 15.

EURO COSMETICS Magazine • Uncovering a cosmetic ingredient that improves well-being and sleep quality by preserving the natural cycle of melatonin • Morgane De Tollenaere, Emilie Chapuis, Amandine Scandolera and Romain Reynaud • Morgane De Tollenaere, Emilie Chapuis, Amandine Scandolera and Romain Reynaud

Figure 1:
Mode of action of Synchronight™

Unfortunately, this precious hormone is affected by internal and external triggering factors. Firstly, the production and expression of the melatonin receptor declines with time, impacting quality of life13, 16, 17. Secondly, the main modulator of melatonin’s natural cycle, included here as an external triggering factor, is the presence of visible light (detected by retina photoreceptors), which modulates alertness and brain activity and delays falling asleep4,18,19. Recently, blue light (a short wavelength of the visible light spectrum) emitted from the screens of digital devices (tablets, smartphones, computers, televisions, etc.) has been put in the spotlight since various studies have reported its ability to enhance alertnessö18. Given the increasing exposure to digital devices during the day and before bed, various scientists have studied the direct effects of this new “pollution”. They reported that exposure to blue light disrupts the circadian rhythm and partially suppresses melatonin levels, and consequently also disturbs sleep physiology (deregulating sleep phases, increasing the number of awakenings during the night and time to fall asleep), next-morning alertness and cognitive reactivity, leading to the rise of sleep-related disorders among the global population20–23. In addition, the long-term effects of melatonin suppression have been correlated to a higher prevalence of cancer, diabetes and metabolic syndromes. From a holistic perspective, it equates to a decline in well-being, therefore5,24,25.
If we look closer at cosmetic concerns, poor sleep quality has been evidenced as a factor disrupting skin integrity26,27,28.

Synchronight™ protects skin from digital stress and contributes to well-being by preserving sleep quality

It is now commonly established and accepted that blue light, close to ultraviolet A (UVA) irradiation, negatively impacts the skin. Beyond the effects on circadian rhythm, various scientific papers have reported numerous effects, such as increased oxidative stress (ROS and RNS production), inflammation and DNA damage, perturbation of the mitochondria network, and degradation of collagen type I through the activation of matrix metalloproteinases20,29–36.
Givaudan Active Beauty developed Synchronight™ to protect the skin by harnessing the blue light filter properties and “melatonin-like” activity of a Gardenia jasminoides fruit extract enriched with crocin and de-rivatives. In trials, Synchronight™ demonstrated powerful protection of mitochondria integrity, antioxidant activity and, most importantly, preserved melatonin’s natural cycle (Figure 1, data not shown). Combined, these produced anti-ageing benefits, evidenced at the clinical level by a significant 21% reduction in the number of wrinkles compared to the placebo37 (data not shown).
In line with our purpose to pursue the development of natural and innovative active ingredients with well-being properties, we pushed back the boundaries of cosmetics to become the first to design a clinical trial for cosmetics covering blue light exposure from electronic devices and sleep quality assessment. This is important, given blue light is now well recognised as a major triggering influence on sleep physiology, leading to a decrease in health and well-being. Based on literature evidencing modulation of melatonin plasma level following the use of transdermal patches38,39, we hypothesised that by protecting the melatonin cycle at the skin level, we may have protected the sleep quality of volunteers.

EURO COSMETICS Magazine • Uncovering a cosmetic ingredient that improves well-being and sleep quality by preserving the natural cycle of melatonin • Morgane De Tollenaere, Emilie Chapuis, Amandine Scandolera and Romain Reynaud • Morgane De Tollenaere, Emilie Chapuis, Amandine Scandolera and Romain Reynaud
Figure 2: Histograms representing the average number of nights without awakenings (after application of a cream containing 2% Synchronight™ a or placebo for 28 (left) and 56 (right) days. Statistical analysis was de-termined using Dichotomic analysis Fisher test with **p<0.01.
EURO COSMETICS Magazine • Uncovering a cosmetic ingredient that improves well-being and sleep quality by preserving the natural cycle of melatonin • Morgane De Tollenaere, Emilie Chapuis, Amandine Scandolera and Romain Reynaud • Morgane De Tollenaere, Emilie Chapuis, Amandine Scandolera and Romain Reynaud
Figure 3: Histograms representing the average number of nights without awakenings (after application of cream containing Synchronight™ at 2% or placebo for 28 (left) and 56 days (right). Statistical analysis was determined using Dichotomic analysis Fisher test with **p<0.01, ***p<0.001.
EURO COSMETICS Magazine • Uncovering a cosmetic ingredient that improves well-being and sleep quality by preserving the natural cycle of melatonin • Morgane De Tollenaere, Emilie Chapuis, Amandine Scandolera and Romain Reynaud • Morgane De Tollenaere, Emilie Chapuis, Amandine Scandolera and Romain Reynaud
Figure 4: Histograms representing the median number of awakenings after application of cream containing 2% Synchronight™ or placebo for 28 (left) and 56 (right) days. Statistical analysis was determined using non-parametric analysis Mann-Whitney test with #p<0.1.

During our innovative double-blind inter-individual and placebo-controlled clinical study, 40 female volunteers (between 18 and 50 years of age) were exposed to blue light through the use of computer tablets, at least two hours before bedtime (for a total of four hours per day). We asked them to record their sleep qual-ity and the number of times they woke in the night in a daily log.
After each night, the volunteers answered three questions:

  1. Was it easy to fall asleep? Yes, it was easy to fall asleep / No, it was hard to fall asleep
  2. Did you wake up in the night? Yes / No
  3. How many times did you wake up?

In a global overview of the daily log’s first assessment (Figure 2), the number of responses “Yes, it was easy to fall asleep” was higher than “No, it was hard to fall asleep”, between 84% and 91%. Nevertheless, the number of “Yes” answers was significantly higher for the group having applied the cream containing 2% Synchronight™ in comparison with the placebo group after 28 days. The difference was still significant after 56 days.
The second assessment of the daily log was the evaluation of the number of nights without awakenings. In Figure 3, we can see that the group that applied the cream containing Synchronight™ had a significantly lower number of nights without waking up than the placebo group (31.06% v 49.48%). After 56 days, the number of nights without awakenings was even lower and stayed significantly different from the placebo group (28.97% v 49.59%).The final evaluation was to measure the number of times volunteers woke in the night. After 28 days, 23 awakenings were counted in the placebo group whereas, in the “active group”, only three were registered, showing a significant variation of 87% in favour of the group that had applied the cream containing Synchronight™. After 56 days, the numbers rose to 41.1 for the placebo group against 7.5 for the active group. The variation between the two groups was 82% and significantly in favour of the active group.

To summarise, the results of our clinical trial evidence a clear and positive impact of Synchronight™ on sleep physiology. The volunteers perceived improvements in the ability to fall asleep and reported a lower number of awakenings and nights without awakenings compared to the group that applied the placebo cream. In our study, this amelioration in sleep quality was also correlated to a well-being improvement, assessed by a questionnaire (data not shown).
Moreover, the results are further supported by two clinical trials (non-exhaustive list) demonstrating the effectiveness of using transdermal patches and skin patches to modulate the melatonin plasma level38,39, thereby evidencing the possibility of impacting the global melatonin level through the skin.
In conclusion, it is well-established that blue light emitted from digital devices has a major triggering factor on sleep quality. The light perceived by the eyes and the skin suppresses melatonin production, delaying the time of falling asleep20,30,31. The physiology of sleep (phases) is disturbed and quality is decreased, leading to alertness and difficulties in waking up with drowsiness during the day4,22,23. Lack of sleep is also well-known to be a prevalent factor in cancer, diabetes and metabolic syndromes, mak-ing it important for human health and well-being24,25.
Since it has been demonstrated that poor sleep quality affects skin integrity, with skin connected to the brain, it seems clear that preservation of melatonin’s natural cycle would have a positive impact on the whole body1,26,27,37.
As unveiled in this paper, the results of our innovative clinical trial have shown how Synchronight™ can re-duce the number of awakenings and increase the sleep quality of the volunteers, evidencing a well-being effect.

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