BEL-EVEN™

Future-proof your skin from the effects of daily stress

EPID

ERM

ISDE

RMIS

SKIN

THI

NNIN

G

STRESS BEL-EVEN™

Decreased keratinocyteproliferation

Keratinocyteproliferation restored

Increased collagen and tissue density

Increased numberof  broblasts

Improved elasticity

Reduced numberof  broblasts

Collagen damage

ECM disorganisation

SKIN BARRIER FUNCTION IMPAIRED IMPROVED BARRIER FUNCTION

cortisol BEL-EVEN™11β-HSD1 enzymecortisone

BEL-EVEN™ – a unique approach to manage your daily stressStress triggers cortisol release in the skin. Small amounts of cortisol helps handle stress, but excessive amounts of cortisol can damage the skin, causing unwanted visible signs of ageing like lines and wrinkles, less elasticity, and reduced barrier functionality. BEL-EVEN™ is a patented synthetic small molecule that helps counteract the damaging effects of stress on skin. BEL-EVEN™ selectively inhibits the enzyme 11β-HSD1, particularly in keratinocytes, but also in fibroblasts, leading to rebalanced cortisol levels. This well-defined mechanism helps your skin to manage the undesired effects of a stressful lifestyle and skin elasticity, density and barrier functionality will improve.

Inhibiting the enzyme 11β-HSD1 reduces cortisol levels, therefore reducing the negative effects cortisol has on the skin.

11β-dehydrogenase(11β-HSD1)

CortisolCortisone BEL-EVEN™

HO

OH

OH

O

OH

H

H

OH

OH

O

O

O

H H

H

K ERATINOCYTE

NUCLEUS

STRESS BEL-EVEN™

NUCLEUS

BEL-EVEN™ inhibits 11β-HSD1,less cortisol is produced

Let DSM ease your stressWhether stemming from job-related issues, relationship conflicts, or simply facing a 24/7 lifestyle, stress has become a constant part of our daily lives. The human skin naturally responds to periods of stress with the formation of more cortisol through a particular enzyme; 11β-HSD1. This release of cortisol, the so-called stress hormone, is a normal and healthy adaptation reflex. However, cortisol can turn into an enemy of the skin if it remains in excess over a long period of time. Beyond practicing stress-coping techniques, there is a high consumer interest for cosmetic treatments that work to both help the skin deal with stress and reverse any negative effects such as skin thinning, loss of elasticity and barrier weakening in general.

With BEL-EVEN™, DSM has designed and patented a new cosmetic ingredient that inhibits in vitro 11β-HSD1. BEL-EVEN™, was specifically developed for skin care applications by using a rational design approach. It locally rebalances the negative, long-term effects of stress on skin. BEL-EVEN™, visibly reduces signs of a stressful lifestyle, for fuller, more supple-looking skin with improved skin elasticity and greater barrier integrity.

Key facts

INCI name

Suggested concentration

Benefits

Cosmetic application

Unique product features

Biphenyl Azepanyl Methanone

1% BEL-EVEN™ for face and body care

• Fights against stress-induced collagen loss and skin thinning• Leads to more supple-looking skin with improved skin elasticity • Significantly improves skin density and greater barrier integrity

• Anti-stress care to rebalance the effects of urban lifestyle• General anti-pollution care• Anti-ageing care, focus on anti-wrinkle and skin elasticity• Spa and well-being concepts

• Offers an effective answer to the effects of daily stress on skin, one of the most burning consumer topics

• Patented new to the world molecule with well-defined innovative mode of action

• Rebalances cortisol level in skin by inhibiting the enzyme 11β-HSD1

• Sustainable production process

Efficacy

100

80

60

40

20

0

% co

llage

n III

sta

inin

g

Ex vivo11β-HSD1 expression in skin increases under stress of UV Irradiation

• Upon UV irradiation (3 J/cm2), expression of 11β-HSD1 increases significantly

BEL-EVEN™ protects the skin in stress test

• BEL-EVEN™ prevents UV-induced Collagen III damage by inhibiting the enzyme 11β-HSD1

• Using 10 µM of BEL-EVEN™ active

No UV

UV-irradiation (dose)

50

40

30

20

10

011β-

HSD1

exp

ress

ion

(sta

inin

g sc

ore)

3 J/cm2

Vehicle no UV

Vehicle 3 J/cm2

UV-stressed

BEL-EVEN™ 3 J/cm2

UV-stressed

Increased Collagen III levels using BEL-EVEN™

BEL-EVEN™ helps to increase the skin density significantly after 4 and 12 weeks. Higher skin density results from increased protein (mostly collagen) content in the dermis.

In vivoBEL-EVEN™ human study visualizes anti-stress effect

The effects of 1% BEL-EVEN™ on aging parameters and barrier stability was tested during a 3 month, placebo-controlled, study on 30 female subjects (50–65 years).

BEL-EVEN™ improves skin elasticity and density

15

10

5

0Incr

ease

d sk

in d

ensi

tiy ve

rsus

t=0

**

4 weeksPlacebo | 1% BEL-EVEN™

12 weeks4 weeks1% BEL-EVEN™ vs placebo

20

15

10

5

0

% ch

ange

of v

erum

vs p

lace

bo

12 weeks

6.4%

**15.7%

* p<0.01 versus t=0 * p<0.01 versus t=0

After 12 weeks of 1% BEL-EVEN™ application, the facial skin elasticity significantly improves by 15.7%. with respect to placebo.

Conclusion

• BEL-EVEN™ treated subjects were statistically significantly (p<0.001) better rated compared to placebo in terms of visual wrinkle development

• BEL-EVEN™ revealed visual effects on the reduction of wrinkles

100

80

60

40

20

0

% d

erm

al co

llage

n st

aini

ng *

**

BEL-EVEN™ protects the dermal collagen network significantly

• Adding BEL-EVEN™ to cells inhibits the conversion of cortisone to cortisol

• Using 10 µM of BEL-EVEN™ active

Vehicle Vehicle 0.1 µM

cortisone

BEL-EVEN™ 0.1 µM

cortisone

More collagen & improved skin density

with BEL-EVEN™

State-of-the-art visual assessment of crow’s feet wrinkles

During the 12 week study, a visible improvement of skin wrinkles was observed

In vivoBEL-EVEN™ protects the skin from stress

Stress, in the study, is defined as change of weather conditions to cool and dry from October to December in Switzerland.

Chan

ge in

TEW

L uni

ts vs

t=0 2

1.5

1

0.5

0

*

4 weeksPlacebo | 1% BEL-EVEN™

12 weeks

* p<0.05 vs t=0

0 weeks

12 weeks

• TEWL of facial skin increased due to seasonal stress in the placebo group. An increase in TEWL means the skin barrier becomes weaker

• In the BEL-EVEN™ group the TEWL stayed low and the skin barrier was stable. The skin was better protected against external stress factors.

© 2018 DSM Nutritional Products, 4002 Basel, Switzerland. www.dsm.com/personal-careAll rights reserved. No part of this brochure may be reproduced, distributed or translated in any form or by any means, or stored in a database or retrieval system, without the prior written permission of DSM Nutritional Products AG (“DSM”). While making reasonable efforts to ensure that all information in this brochure is accurate and up to date, DSM makes no representation or warranty of the accuracy, reliability, or completeness of the information. Use of this information shall be at your discretion and risk. Nothing herein relieves you from carrying out your own suitability determinations and tests and from your obligation to comply with all applicable laws and regulations and to observe all third party rights. The uses and claims for DSM’s products recommended in the brochure should be adapted to the current local regulatory environment. We disclaim any and all liability in connection with your product or its use.

P0088

EuropeDSM Nutritional Products Europe Ltd.P.O. Box 2676, 4002 BaselSwitzerlandPhone: +41 61 815 7777Fax: +41 61 815 7860Email: info.pc-emea@dsm.com

Asia PacificDSM Singapore Industrial Pte Ltd.trading as DSM Nutritional Products Asia Pacific30 Pasir Panjang RoadMapletree Business City #13-31Singapore 117440Phone: +65 6632 6617Fax: +65 6632 6600 Email: info.pc-apac@dsm.com

North AmericaDSM Nutritional Products, LLC45 Waterview Boulevard, Parsippany, NJ 07054United States of AmericaPhone: +1 800 526 0189Fax: +1 973 257 8580Email: info.pc-na@dsm.com

Latin AmericaDSM Produtos Nutricionais Brasil S.A. Avenida Engenheiro Billings, 1729 – Prédio 31Sala A - CEP:05321-010, São Paulo – SP BrasilPhone: + 55 11 3760 6409Fax: + 55 11 3760 6492Email: info.pc-latam@dsm.com