CLR Berlin
Skincare and wellbeing
Well-formulated products can have a positive effect on wellbeing which goes beyond the general feel-good factor of applying skincare. The skin–brain connection is not a one-way street, however. In reality, there is a permanent feedback loop between the skin and the brain. As was mentioned above, skincare can influence the brain (wellbeing), but our emotional state of mind can influence our skin as well. Skincare products which aim to fully answer he need of the consumers with a holistic approach to their overall health and wellbeing should act on the entire feedback loop – not just the segment between the skin and the brain, but also the return of this loop back from the brain to the skin. This is what was aimed for with AnnonaSense CLR™ in a new study which was performed in 2023.
Going full circle with the skin–brain connection
A study was performed on a total of 117 volunteers (female, 41.1 +/– 8.1 years y/o). The Purpose of the study was to confirm earlier results and to prove that AnnonaSense CLR™ is indeed a true wellbeing-cosmetic active ingredient by determining its activity on the other half of the skin–brain feedback loop, where the effect of emotional wellbeing was correlated with systemic effects and corresponding skin parameters.
Volunteers were divided over six sub-cohorts. Sub-cohort 1 included people with self-perceived sensitive and/or atopic skin who applied an oil-in-water cream containing AnnonaSense CLR™ at 3% for four weeks. The same cream was applied by subcohort 2 which included a group of People who had a self-perceived stressful life. An important percentage of this sub-cohort were healthcare workers with irregular work hours and a stressful job. Sub-cohort 3 was analogous to sub-cohort 1 but applied the identical formulation as sub-cohort 1 without added AnnonaSense
CLR™ (“placebo”). Sub-cohort 4 was analogous to sub-cohort 2 but applied placebo. Sub-cohort 5 was analogous to sub-cohorts 1 and 3 but performed a facial massage in addition to the application of placebo (“placebo + massage”). Sub-cohort 6 was analogous to sub-cohorts 2 and 4 and performed facial massage in addition to the placebo.
AnnonaSense CLR™ vs. placebo vs. placebo and facial massage
Comparing verum with placebo is essential in determining the biological activity of a cosmetic active ingredient, its real added value. Sub-cohorts 5 and 6 additionally performed a facial massage where these volunteers had expressed their liking for facial massage before the start of the study. It is well known that facial massage can have positive outcomes for both skin and mental wellbeing, and “placebo + facial massage” could therefore be considered to be a “positive control”.
It is important to note that the application of verum and placebo took place in a standardized fashion. For sub-cohorts 5 and 6 the facial massage was performed in a standardized fashion after application of the placebo too. The above-described treatments took place twice daily for a period of 4 weeks.
Introduction of tested parameters: Skin–brain feedback loop = Skin–brain–endocrine feedback loop
An important participant in the skin–brain feedback loop is our body’s endocrine system. The endocrine system is a messenger system which comprises feedback loops of hormones that are
released by internal glands directly into the body. These strongly influence the functionality of organs, such as the skin (see figure 1).
Skin appearance and skin comfort
The appearance of skin can have an important impact on a person’s self-confidence and self-esteem. (Perceived) skin quality is an important determinant of consumer wellbeing. Skin discomfort can also have an important impact on wellbeing. Sensitive skin has been defined as the occurrence of unpleasant sensations in response to stimuli that normally should not provoke such sensations, usually without a visible manifestation. About 50% of the world’s population perceives their skin to be sensitive.
Study methods
Skin appearance and skin comfort were assessed before the start (t = 0) and at the end of the study (t = 4 weeks). Skin appearance was determined by an expert assessor. In addition, standardized photographs were taken.
At t = 0 and t = 4 weeks, the expert assessor graded the redness (erythema) of skin around the nostrils, on the cheeks and nasolabial folds on people with self-perceived sensitive and/or atopic
skin who used verum (containing 3% AnnonaSense CLR™), placebo (w/o AnnonaSense CLR™) and placebo + facial massage (sub-cohorts 1, 3 and 5, as described above) according to the following scores:
- No erythema: 0
- Slight, patchy erythema: 0.5
- Slight, uniform erythema: 1
- Moderate, uniform erythema: 2
- Strong erythema: 3
- Strong erythema, spreading outside graded area: 4
The activity of AnnonaSense CLR™ on increasing skin comfort was determined by a Capsaicin Facial Neurosensitivity Test. Reduction of capsaicin-induced skin irritation can be interpreted to be an important trait for a cosmetic active ingredient which additionally improves wellbeing.
Skin appearance – Results
At the end of the study (t = 4 weeks), the treatment with 3 % AnnonaSense CLR™ had led to a significant reduction of skin redness for all three assessed facial areas when compared to the start of the study (t = 0). Interestingly, the treatments with placebo and placebo + massage had led to an increase in skin redness (see table 1 and diagrams 1, 2 and 3).
Table 1: Relative difference in redness, t = 4 weeks vs. t = 0 (%), based on mean scores.
Diagram 1: Nostrils, relative difference in redness, t = 4 weeks vs. t = 0 (%).
Diagram 2: Cheeks, relative difference in redness, t = 4 weeks vs. t = 0 (%).
Diagram 3: Nasolabial folds, relative difference in redness, t = 4 weeks vs. t = 0 (%).
Wellbeing
Wellbeing is recognized as an important factor in people’s overall quality of life, and over the years reliable methods of measurement have been developed. In general, the use of questionnaires to measure subjective parameters is well-established.
Study method and results Questionnaires were filled out by the study participants at thestart and end of the study (t = 0 and t = 4 weeks, respectively). For both groups of sub-cohorts, intuitively obvious statements related to psychological wellbeing and look and feel of skin were combined with an interest in quality of sleep.
For the volunteers with self-perceived sensitive and/or atopic skin, a significant improvement could be achieved with the fourweek, twice-daily application of 3% AnnonaSense CLR™ concerning the perception of psychological stress, overall positive outlook on life and quality of sleep. See diagram 5.
For the volunteers with a self-perceived stressful life (many of whom were healthcare workers) similar results were obtained.
The treatment with verum had led to a perceivable improvement of quality of sleep and reduction of psychological stress. At the end of the study, the volunteers additionally reported to be more
satisfied with how their skin looked and felt as compared to at the beginning of the study. See diagram 6.
The use of AnnonaSense CLR™ was shown to lead to remarkable results for people who have a stressful life and those who don’t. Even more pronouncedly positive results could be achieved
in people with self-perceived sensitive and/or atopic skin, making AnnonaSense CLR™ an important cosmetic active ingredient for half of the world’s population (at least 50% of all people perceive their skin to be sensitive).
Cortisol
Cortisol represents an important bridge in the skin–brain feedback loop, from the brain back to the skin. It is the primary stress hormone in humans, regulating a wide range of stress responses.
For common skin diseases it is well described that systemic cortisol levels correlate with the severity of the disease. On the one hand, elevated cortisol has a causative role in these diseases and, on the other, is a consequence of the diseases.
Study method and results
Systemic cortisol levels were determined for sub-cohorts 1,3 and 5 at t = 0 and t = 4 weeks by collecting saliva samples using a Salivette Cortisol swab kit (Sarstedt, Germany) which were then analyzed by ELISA for cortisol levels.
It could be shown that the four-week, twice-daily application of 3% AnnonaSense CLR™ had led to a significant reduction of systemic cortisol levels, by more than 33%. This was clearly not the
case for placebo and placebo + facial massage. See diagram 7.
The result obtained with AnnonaSense CLR™ on systemic cortisol is very important and, to the best of our knowledge, is a first for the cosmetic industry: a cosmetic active ingredient cannot just improve skin and wellbeing, it can also significantly reduce systemic cortisol.
Skin health
Health is an active process that enables an organism or organ to adapt to fluctuations in its intrinsic and extrinsic environments to maintain biological homeostasis or recover its biological homeostasis quickly. Health strongly and directly correlates with wellbeing.
Systemic cortisol, produced inside the body, reduces skin health.
Study method and results
It has been shown in the scientific literature that measuring the kinetic of skin barrier recovery after disrupting this barrier is a reliable method to determine skin health in the context of psychological stress–induced reduction of skin health.
In the studies described here, a comparison was made between the rate of barrier recovery on skin treated with 3% AnnonaSense CLR™ and placebo, after four weeks of twice-daily application of these test products on the inner forearm. At t = 4 weeks, barrier damage was induced at the test sites using an adhesive tape (Blenderm™) to remove the stratum corneum layers until TEWL
(transepidermal water loss) values were increased 20% or more compared to t = 0 baseline values. Then the kinetic of the barrier recovery process was determined by measuring TEWL.
It could be shown that the treatment with verum improves skin health, with the speed of barrier recovery being more than 17% faster compared to the skin which was treated with placebo with
the same frequency for the same amount of time. See diagram 8.
3% AnnonaSense CLR™ improves skin health, which correlates elegantly with its activity on reducing systemic cortisol, but also correlates with its potency in improving skin comfort and appearance.
This activity is essential as it shows that AnnonaSense CLR™ has positive effects on all stages within the skin–brain–endocrine feedback loop.
Conclusions
The results of the new studies which were performed with AnnonaSense CLR™ in 2023 on a total of 117 volunteers are summarized in figure 4. Skincare with 3% AnnonaSense CLR™ improves
skin appearance, skin comfort and wellbeing. These are important results but only represent one half of the popular skin–brain connection.
Within four weeks, 3% AnnonaSense CLR™ could additionally reduce systemic cortisol levels and, in correlation with this activity, also improved skin health. Altogether, AnnonaSense CLR™ is,
to our knowledge, the first and only cosmetic active ingredient with a real, complete and significant effect on the skin–brain connection–a real neurocosmetic/psycare/neuroglow ingredient, if you will.
3 % AnnonaSense CLR™.
