NATUROPATHIC AESTHETICS: ACNE VULGARIS · • Key cosmeceutical product categories • Role of the skin barrier and in -depth look at topical ceramides • Quick Look: Skin surface

NATUROPATHIC AESTHETICS: ACNE VULGARIS

BEYOND THE TEXTBOOK APPROACHES TO MANAGING ACNE VULGARIS

Copyright Rob Aroup Reproduction and distribution of this presentation without written permission from the author is prohibited.

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COURSE OUTLINE• Brief review of Acne Vulgaris

• Overview of conventional treatments • Recap of common Naturopathic treatments

• Acne assessment tools• Cosmeceuticals & acne…common myths• Key cosmeceutical product categories

• Role of the skin barrier and in-depth look at topical ceramides• Quick Look: Skin surface pH and acne…the role of the ‘acid mantle’ • Cleansers and specialty cleansing products• Quick Look: Cleansing assessment and frequency recommendations• Moisturizers and serums• Toners, masks, and oil-absorbers• Spot treatment of acne lesions

• Key cosmeceutical ingredients in acne management• Primary cosmeceutical considerations• Cosmeceutical actives for reducing oiliness• Cosmeceutical actives for reducing inflammation• Cosmeceutical actives for preventing/reducing post-inflammatory hyperpigmentation• Cosmeceutical actives for managing facial redness and skin sensitivity

• Novel oral supplements for acne management• Quick Look: Emerging role of the skin microbiome and acne

• Oral & Cosmeceutical probiotics in acne• Putting it all together…methods of integration into your aesthetic practice


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ACNE: A BRIEF REVIEW• Frequency and who’s affected?...

• Noted as the most common dermatologic disorder, acne vulgaris affects between 40 and 50 million individuals of all ages in the United States.

• 85% of those between 12 and 24 years of age will experience some acne (prime age where cosmetic and psycho-social impact may be heightened)

• Acne can persists into the 20s and 30s in approximately 64% and 43% of people, respectively.

• The heritability of acne is almost 80% in first-degree relatives

• Disease of the pilosebaceous unit: follicle (pore), sebaceous gland, and hair

• Primary lesion (drum roll)…the microcomedo, the result of sebum and keratin blockage due to increased proliferation and decreased desquamation of follicular keratinocytes

• Microcomedo can progress into open or closed comedones, as well as inflammatory lesions such as papules, pustules, nodules, and cysts

• Key pathogenic factors involved in acne formation:• Follicular hyperkeratinization (leading to microcomedo) • Sebaceous gland hyperactivity (androgen-induced)

with excess sebum production• Colonization of the (lipid-rich & anaerobic) follicle by

Propionibacterium acnes• Inflammatory response/mediators in skin (triggered

owing to the presence of P.acnes)

Zaenglein AL & Thiboutot DM. Acne Vulgaris. In Dermatology, 4th ed., edited by Bolognia, JL, Schaffer, JV., & Cerroni, L. 36, 588-603.e1 . Elsevier, 2018


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ACNE: A BRIEF REVIEW• Further details surrounding the key pathogenic factors…

• Triggering a cascade…• P.acnes stimulates the innate immune response via Toll-like receptors (TLRs). • This sets off an inflammatory cascade of keratinocyte cytokine formation, including interleukin-1alpha

and tumor necrosis factor-alpha, among others. These cytokines are also believed to contribute toward further aberrant follicular hyperkeratinisation

• Quality, not quantity…• Although increased sebum production is characteristic of acne, the seborrhea in-of-itself is not

sufficient to produce acne. • Evidence indicates that sebum composition (lipid quality) and not quantity plays a key role in acne

development…• Desaturation of the fatty acids in sebum may contribute toward acne lesions. • Reduction in linoleic acid levels in sebum affect sphingolipid and ceramide levels (more on this later)• Accumulation of lipid peroxides characterize the sebum of acne patients, and this, along with other qualitative

changes in the sebum lipids, trigger alteration of keratinocyte differentiation and induce interleukin-1 (IL-1) secretion, together leading to follicular hyperkeratinization

• Will the real pathogenic P.acnes please stand up?...• The anerobic, gram positive P.acnes is naturally part of the skin’s normal flora (more on the

microbiome later…)• Studies are now turning their attention to determining if different pathogenic forms of this bacteria

may be the true culprit in inflammation and acne formation • Breaking the barrier…

• Evidence is accumulating regarding the contributing role stratum corneum barrier dysfunction can play in the pathogenesis of acne. More on this coming up…


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ACNE: A BRIEF REVIEW

Botros, PA et al. Evaluation and management of acne. Prim Care Clin Office Pract 42 (2015) 465–471


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ACNE: A BRIEF REVIEW

Zaenglein AL & Thiboutot DM. Acne Vulgaris. In Dermatology, 4th ed., edited by Bolognia, JL, Schaffer, JV., & Cerroni, L. 36, 588-603.e1 . Elsevier, 2018


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QUICK LOOK: TEXTBOOK NATUROPATHIC APPROACHES TOWARD ACNE

• DIETARY• Dairy milk/products reduction or elimination: • Theorized to be implicated owing to the hormonal content found in dairy products…including

estrogens, progesterone, androgens, glucocorticoids, and insulin-like growth factor-1 (IGF-1)• A number of acne-IGF-1 connections exist:

• Elevated IGF-1 has been observed in adults with acne• IGF-1 levels in women with acne correlate with total acne lesions, inflammatory lesions, as well as

with serum levels of DHT and DHEA-S• A correlation between facial sebum excretion rate and serum IGF-1 levels has been shown in

those with post adolescent acne• IGF-1 can increase the synthesis and bioavailability of androgens through inhibition of sex

hormone-binding globulin synthesis in the liver

• Low-glycemic load diet: • Represents the rate of carbohydrate absorption (indicated by the glycemic index) and the

quantity of carbohydrate consumed; used as means to limit the food-related increase in blood glucose and insulin. Several connections to acne have been made…

• Can reduce/prevent IGF-1 and insulin elevations • Can reduce testosterone bioavailability and dehydroepiandrosterone sulfate concentrations,

possibly explained by the insulin lowering effect above• An effect on sebum quality?...One study showed not only a reduction in total acne lesion count,

but also an increase in the Saturated Fatty Acid-to-Monounsaturated Fatty Acid ratio in sebum. Here, such an increase in this ratio was predictive of clinical improvement in acne measures. Theories for this include the notion that MUFAs (such as oleic acid) can interfere with the skin barrier by replacing linoleic acid in ceramide structure, affecting barrier flexibility and function; additionally, MUFAs have been observed to induce hyperkeratotic effects similar to those seen in comedo formation


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• Anti-inflammatory Diet: • A whole-food, plant and fish-rich, animal product-reduced eating pattern

may contribute via a few general mechanisms:• Limiting consumption of dairy milk and high glycemic load foods as discussed• Increasing the influence of EPA/DHA anti-inflammatory effects in skin, helping

to minimize/manage inflammatory acne lesions and support optimal wound healing

• Further anti-inflammatory support via a high antioxidant intake • General health benefits from an increase in macro/micronutrient intake• Need to inject more vegetable variety for your patients?...Have them try this

great ‘Vegetable Advisor’ tool from whfoods.org: www.whfoods.com/vga.php

• ‘5 Days-A-Week’ Pescitarian…my clinical experience



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http://www.whfoods.com/vga.php

http://www.whfoods.com/vga.php

• NUTRITIONAL SUPPLEMENTATION • Essential Fatty Acids (Omega-3s)• Further to their central role in the anti-inflammatory diet discussed above, marine

sources of Omega-3s provide various lines of benefit… • As a means of reducing various inflammatory mediators, such as the inflammatory

signaling molecule leukotriene B4 (LTB4), speculated to play a key role in inflammatory acne lesions

• Have demonstrated the ability to reduce IGF-1 levels in male subjects• EPA and DHA are natural ligands for the peroxisome proliferator-activated receptor

(PPAR), expressed on adult keratinocytes, Langerhans cells, and melanocytes. Various isotypes of the PPAR are noted for their anti-inflammatory properties

• New lines of evidence show that EPA and DHA may help modulate the inflammatory response initiated by the P.acnes activation of various Toll-like receptors found on macrophages and sebocytes

• Typical dosage is 1-3g of combined EPA and DHA components, if supplementing; dietary intake is always recommended to complement supplemental intake



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• HERBAL MEDICINES • Some of the more common herbal categories considered in the management

of acne include (internal or topical use, where applicable):• Alteratives (especially Hepatic alteratives)

• Such as Echinacea sp., Burdock, Cleavers, Stinging Nettle• Capitalizing on their elimination, cleansing, and detoxifying roles, particularly in

the context of chronic skin inflammation• Anti-microbials

• Such as Oregon grape root (and other berberine containing herbals), Licorice root, Yarrow, Myrrh, topical Tea tree oil

• To help attenuate presence and influence of P.acnes• Anti-inflammatories

• Such as Turmeric root, Yarrow, Oregon grape root, Myrrh, Licorice root• To gently modulate degree and severity of inflammatory lesions

• Hormonals• Such as Chaste tree, Saw Palmetto, and Licorice root• To help modulate hormones in managing premenstrual acne, or any hormone-

related acne development through peri-menopause (Chaste tree); and to help mitigate the influence of excess androgens (Saw Palmetto & Licorice root)

• Lymphatic tonics• Such as Cleavers & Stinging Nettle• To support lymphatic drainage both from the skin as well as surrounding tissues



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• Homeopathy• According to details of case picture/presentation• Some practitioners may include constitutional homeopathy, others may use homeopathic

‘combination’ remedies designed for skin concerns• Homeopathic-based lymphatic products (oral and/or topical) have also been frequently

used• Traditional Chinese Medicine• Treatment based on TCM pattern, typically relating to the presence and effects of

Dampness & Heat• Can include the full range of TCM treatment

• Dietary adjustments based on TCM philosophy• TCM Herbal medicine (oral/topical)• Acupuncture point selection based on:

• Pattern treatment• ah shi points• Surround the Dragon points for spot treatment• Auricular point selection• Cupping, blood letting, etc.

• Specialty Acupuncture (Cosmetic): Example of a cosmetic technique…• Placement of multiple short needles (ex. up to 10-15 in total over face, 0.16-0.20 x 15mm)

across unaffected skin; needle tapped into skin enough to stand freely upright (at or near 90oinsertion), no need to obtain De qi sensation

• Benefits via localized circulatory support (perhaps other mechanism?)



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• Why Assess?...• Assessment of acne severity can, like most assessment measures, seek to

objectify and highlight changes noted over time• Can provide an effective and corroborative means of determining success of

treatment strategies• The challenge of achieving a consensus…

• At least 25 different acne severity grading systems have been used in acne research studies

• The two most common formats have been global assessments and lesion counting

• Global severity gradings…• Based on a comparison of descriptive text or photographic standard • Believed to be better suited to clinical practice since it is less time-consuming

and emphasises disease activity• Can still be subject to minor subjectivity

• Lesion counting…• The number of open and closed comedones, papules, pustules, and nodules

are counted• Generally seen to be more useful in research settings. • Subjectivity can still occur in relation to how lesions get classified.

ACNE ASSESSMENT TOOLS


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1. Global severity grading methods:• Global Acne Grading System (GAGS)• Divides the face, chest, and back into 6 distinct

areas (forehead, each cheek, nose, chin, and chest/upper back)

• A ‘Factor rate’ of 1-3 is given to each area based on its size

• A second ‘clinical assessment’ factor of 0-4 is then assigned to each region depending on the most severe lesion type found in the assessed region (no lesions = 0, comedones = 1, papules = 2, pustules = 3, and nodules = 4).

• The two factors are then multiplied giving the score for each area

• The overall score is consequently the sum of all area scores

• A score of: • 1-18 is considered mild • 19-30 = moderate• 31-38 = severe• >39 = very severe


Hajheydari, Z. et al. Effect of Aloe vera topical gel combined with tretinoin in treatmentof mild and moderate acne vulgaris: a randomized, double-blind prospective trial. Journal of Dermatological Treatment, 2014; 25: 123–129


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• Comprehensive Acne Severity Scale (CASS)• A validated 6 category-based scale used to

assess the face, back and chest• Used as an outcome measure for regulatory

drug approval in the United States• Has shown high correlation with the Leeds

Technique (see next slide)

• Method of Use: Inspect patient’s face, back and chest at a distance of 2.5 meters (approx. 8 feet); grade each according to chart description


Becker, M. et al. Objective assessment of acne. Clinics in Dermatology (2017) 35,147–155


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• Others to consider:• Leeds technique (1998 revised version): • For those who prefer a more visual-based photo-numeric system• Consists of a numeric severity scale of 0-10; Areas examined are the face,

chest, and back. • The severity is determined by comparison with a set of reference

photographs• For more info on the Leeds technique see: O’Brian SC, Lewis JB, Cunliffe WJ.

The Leeds revised acne grading system. J Dermatol Treat. 1998;9:215-220

• Curious about lesion count?...


Botros, PA et al. Evaluation and management of acne. Prim Care Clin Office Pract 42 (2015) 465–471


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2. Conventional flash photography• A simple, readily available method of documenting

changes over time• Best obtained in a standardized fashion/photographic

environment • For further details on cosmetic photography, see ‘Tips

for Taking Before & After Photographs’ section in Assessment in Naturopathic Aesthetics CE Course (NaturopathicCE.com); and/or refer to the following reference:

• Alibhai H. Introduction to Aesthetic Medicine. In Pfenninger JL & Fowler GC (Eds.) Pfenninger and Fowler's Procedures for Primary Care, 3rd Ed., Elsevier-Mosby (2011),46,291-295

• New cameras on the block…• In addition to conventional photography, newer

techniques such as fluorescence photography, polarized light photography, video microscopy, and multispectral imaging (MSI) have been developed and adapted to attain further objective measurements in acne vulgaris assessment


General Tips for Cosmetic Photography

• Ideally, all photographs should be taken in a designated room using a blue/navy background

• Lighting, distance, background, and views taken should be duplicated for both the before and the after photographs

• Additional background options include: dark solid wall color, poster board, felt, blue window shade/blind mounted on the back of a door

• Limited or no jewelry for both before and after photographs• Hair pulled away from the face• Views of affected areas should be consistent:

Full face/oblique/profile/close-up of treatment area(as example of lesion type/severity)/general area of upper back or upper chest


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3. ACNE-Q

• Part of a growing series of patient reported outcome measures (PROMs) used to evaluate outcomes, effects, quality of life, and patient satisfaction

• Collects and compares evidence-based outcomes data

• Field-tested in patients aged 12 years of age and older with facial, back and chest acne and/or acne scars

• Includes scales to measure personal appraisal/appearance, scarring, and psychosocial aspects of acne


Source: http://qportfolio.org/, users guides for ACNE-Q, v1.0, Sept., 2018

Scales in ACNE-Q


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http://qportfolio.org/


• Minimizing the language barrier…Scales are available in multiple languages

• A multitude of scales beyond acne…Scales have also been developed for various concerns: SCAR-Q, BREAST-Q (Augmentation/Breast Cancer/Reduction-Mastopexy), FACE-Q (Aesthetic concerns, Head & Neck Cancer/Skin Cancer), among others

• Easy to access, and free to use…• Currently, these assessments are free for non-

profit and clinical use…just click the ‘Request Module’ link from the website address below

• See http://qportfolio.org/ and/or http://qportfolio.org/acne-q/ for more information and to request your copies of the ‘Qs’ your aesthetics practice needs


ACNE-Q• Can be tailored according to need…Patients are not required to complete all scales within the category, as

each individual scale can be used independent of the others• Simplified scoring…there is no total/overall score for the ACNE-Q, simply the individual scores for the

independent scales; each scale’s raw score is added and converted into a score of 0-100. The users guide and/or scale will indicate and review the interpretation of both high and low scores for a given scale

• Validation…Each scale has been extensively field tested


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4. Skin Oiliness Scale• A validated subsegment from the Baumann

Skin Type Indicator Questionnaire • A 6-item scale correlating with sebumeter

measurements to help identify and quantify degree of skin oiliness

• Beyond self-assessment…• Authors of the scale highlight how studies show

that asking patients if they have dry, oily or normal skin, does not fully correspond with sebumeter ratings

• Methodically designed questions, such as those in this scale, do correlate with sebumeter measurements in reviews to date

• Method of use: • Completed by patient• Score range of 0-26 (Answer of ‘a’ = 1 point, ‘b’

= 2 points, etc.) • No threshold score, the higher the score =

greater degree of skin oiliness• Can also compare to reference mean score for

each question (see table on next slide)


Baumann, L.S., Penfield, R.D., Clarke, J.L. and Duque, D.K. (2014) A Validated Questionnaire forQuantifying Skin Oiliness. Journal of Cosmetics, Dermatological Sciences and Applications, 4, 78-84.


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Both images from: Baumann, L.S., Penfield, R.D., Clarke, J.L. and Duque, D.K. (2014) A Validated Questionnaire forQuantifying Skin Oiliness. Journal of Cosmetics, Dermatological Sciences and Applications, 4, 78-84.


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5. Perceived Stress Scale

• A scale used in acne research to showcase the correlation between stress and graded acne severity, as well as acne lesion exacerbations

• Most studies looked at mild-moderate acne in high school and university aged populations around the time of examination period

• Postulated connection… • Authors of one study suggest that the effect of stress on acne

severity relates not to the secretion or quantity of sebum per se, but rather to an enhanced production and release of neuropeptides (and related inflammatory mediators), as well as an influence on the lipid composition within sebum as well.

• Substance P and corticotropin releasing hormone are examples of these cutaneous-influencing neuropeptides (keep Substance P in mind for our discussion on probiotics)

• Highlights the need and role for stress management approaches as part of acne support…

• Ex. relaxation techniques, dietary adjustments, adaptogenic herbs and/or stress-supportive supplements such as L-Theanine



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• A good example for the strength of the ‘Naturopathic’ term in ‘Naturopathic Aesthetics’

Cohen, Sheldon. “Perceived Stress Scale.” Mind Garden, www.mindgarden.com/132-perceived-stress-scale#horizontalTab2.

Obtain your copy of the PSS from: https://www.mindgarden.com/132-perceived-stress-scale



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A QUICK REVIEW

• Key pathogenic factors involved in acne formation:• Follicular hyperkeratinization • Sebaceous gland hyperactivity & excess sebum production• Colonization of follicle by Propionibacterium acnes• Inflammatory response

• Textbook approaches to managing acne vulgaris• Acne assessment tools

• Global Acne Grading System (GAGS)• Comprehensive Acne Severity Scale (CASS)• Lesion Count• Clinical Photography• ACNE-Q• Skin Oiliness Scale• Stress Questionnaires (ex. Perceived Stress Scale)


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ACNE-BASED COSMECEUTICAL MYTHSMYTH

Those cosmeceuticals labeled non-comedogenic or non-acnegenic, will not produce acne if used

• Non-comedogenic and non-acnegenic are marketing claims carrying no implied regulation

• To make the claim of true non-comedogenicity, rabbit ear or human comedogenicity testing would typically be performed. Both the animal and the human model are based on the presence of new comedone formation after the exposure of skin to the finished cosmetic. Human testing is considered to be more accurate

• Based on the safety profiles of the individual ingredients in their formulations, numerous manufacturers often make noncomedogenic and non-acnegenic claims. This is not accurate

• These claims should be made and based on clinical testing of the finished formulation. Confirming this to be the case with the manufacturer is highly recommended

MYTHMineral oil is strongly comedogenic

• One of the most common ingredients in skin care products and colored cosmetics is that of mineral oil

• Although it is often listed as a comedogenic cosmeceutical ingredient, it was originally included in these list’s years ago, and likely based on the effect of industrial grade mineral oil, which can be comedogenic

• Cosmetic grade mineral oil is what should be sought, as it is the purest form with no contaminants. It is designed for skin application, and noncomedogenic

Adapted from Draelos Z.D. (2016) Acne cosmeceutical myths. In Draelos Z.D. et al (Eds.), Cosmeceuticals, 3rd ed Elsevier (p. 183-186).


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ACNE-BASED COSMECEUTICAL MYTHSMYTH

Sunscreens cause acne

• A true breakout?...Some patients may characterize the occurrence of ‘breakouts’ following the use of sunscreens. These patients typically present with perifollicular papules and pustules in a random distribution over the face. This eruption can appear within 1-2 days after wearing a facial sunscreen

• A quick review of physical and chemical sunscreen ingredients…All of the UVB sunscreens and avobenzone function by transforming UV radiation to heat energy. It’s this heat energy which may be noticed by those patients (who state that they do not like wearing sunscreens, since the gels or lotions make them feel hot)

• A sweating issue…This increased sweating induced by the sunscreens, and accompanied by the warm or sunny weather, may cause an increase in the eccrine gland activity. This, in turn, may lead to miliaria rubra (aka ‘prickly heat’ or ‘sweat rash’) which may be amplified by the occlusive nature of the water-resistant, rub-proof product

• What’s likely going on…This sunscreen-induced breakout is instead likely the formation of papules or pustules around the eccrine duct ostia, without the sebaceous gland involvement that characterizes true acne.

• Perhaps the use of sunscreens with zinc oxide (physical blocking sunscreen)added antioxidant and/or anti-inflammatory cosmeceutical ingredients may mitigate against this potential process

MYTH Cosmeceuticals can effectively

reduce pore size

• A marketing thing?...Although it’s a popular marketing claim, there is a lack of definitive evidence that certain cosmeceuticals can measurably reduce pore size in of itself.

• Two popular exfoliants are sometimes attributed this effect: glycolic acid and salicylic acid.

• Glycolic acid…an exfoliant which, owing to its water soluble nature, cannot enter into the oily milieu of the pore. As such, it is unable to offer exfoliating effects from within the pore. It can, however, increase skin smoothness, thus seemingly appearing as reduced pore size, without any actual size change.

• Salicylic acid…by contrast, is oil soluble. As such it can, and does, enter into, exfoliate, and remove debris from the pore. It too can create the appearance of smooth skin. In this case, debris removal can technically reduce the size of a dilated pore (dilated to accommodate the debris presence). However the physical size of the debris-less/resting pore cannot be changed.



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ACNE-BASED COSMECEUTICAL MYTHS

MYTH Acne breakouts after the age of 30 in women are rare and only require

skincare products for their management

• Acne after age 30 is reported to be more common in women• Hormone influence…It is theorized that, given its preponderance of

inflammatory lesions (papules, pustules) over non-inflammatory lesions (open/closed comedones), hormonal fluctuations surrounding pre/peri-menopause may be a contributing factor

• A deeper approach needed…The use of skincare products alone is likely not enough, given the deep-seated nature of inflammatory lesions.

• As such, conventional approaches (such as antibiotics or hormone therapy), and/or internal Naturopathic approaches (such as dietary adjustments, nutrient/herbal-based hormonal and inflammatory support, and TCM/Acupuncture therapies) may be needed for full management



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KEY COSMECEUTICALS IN ACNE: CERAMIDES

• Ceramide-based Cosmeceuticals

• Before all else…build and protect the skin barrier!

• ‘Brick & Mortar’ design of the Stratum Corneum…• The bricks represent the terminally differentiated keratinocytes, embedded

within a lipid matrix, representing the mortar, which are arranged into lamellar layers (multiple bilayers) comprised of ceramides (40-50%), free fatty acids (10-15%) and cholesterol (25%)

• It’s role…• The skin barrier plays an essential role in water retention and in the protection

against a wide array of external insults. For example, the phytosphingosine component of ceramide structure exhibits direct anti-microbial activity against P.acnes

• Handle with care…• Disruption or depletion of stratum corneum lipids can weaken the integrity of

the barrier function, and give rise to the progression of various skin concerns, such as dry skin, psoriasis, acne, and atopic dermatitis. All of these conditions have been associated with an alteration and/or depletion of these stratum corneum lipids, and ceramides in particular

• A key realm of cosmeceuticals…• Clinically, ceramides are being added to cosmetic products as a means of

replenishing skin ceramide content, and to improve skin barrier functioning. • Of the stratum corneum lipids, ceramides are the most effective at restoring

barrier function and increasing hydration of skinBoth images from: Dasgupta BR et al (2016). Cosmeceuticals: Function and the skin barrier.In Draelos Z.D. et al (Eds.), Cosmeceuticals, 3rd ed. Elsevier (p. 3-9).


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• Structure & Production of Ceramides• Base structure of a ceramide: a fatty acid conjugated to

a sphingoid base via an amide bond • Heterogenicity is a good way to describe it…In human

skin there are 4 different sphingoid bases and 3 types of fatty acids identified thus far, leading to a current total of 12 different classes of ceramides

• Example of a dietary connection…Linoleic acid is a key free fatty acid needed in the formation of long-chain ceramides, which predominate in the stratum corneum

• Updated Nomenclature (and what you might now see on ingredients labels)…

• Ceramide ‘XY’, where…• X represents the type of free fatty acid moiety (this can be

non-hydroxy (N), α-hydroxy (A) or ester-linked ω-hydroxy (EO))

• Y represents the sphingoid moiety (which can be sphingosine (S), dihydrosphingosine (D), phytosphingosine (P) or 6-hydroxy-sphingosine (H))

• As such, ‘Ceramide EOP’ represents the esterfied ω-hydroxy-fatty acid (EO) conjugated to a phytosphingosine (P) moiety. Meckfessel MH & Brandt SB. The structure, function, and importance of

ceramides in skin and their use as therapeutic agents in skin-care products. J Am Acad Dermatol 2014; 71:177-84


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Ceramide production:• What starts in the stratum basale…

Meckfessel MH & Brandt SB. The structure, function, and importance ofceramides in skin and their use as therapeutic agents in skin-care products. J Am Acad Dermatol 2014; 71:177-84

Tessema EN et al. Potential Applications of Phyto-Derived Ceramides in Improving Epidermal Barrier Function. Skin Pharmacol Physiol 2017; 30:115–138


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Sahle FF et al. Skin Diseases Associated with the Depletion of Stratum Corneum Lipids and Stratum Corneum Lipid Substitution Therapy. Skin Pharmacol Physiol 2015;28:42–55

Ceramides…A clinical snapshot


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• Ceramides in Acne: Growing Role of the Skin Barrier

• Expanding the knowledge base for acne pathophysiology…

• In addition to the focus on the likes of hyperkeratinisation, Propionibacterium acnes, sebum production, and follicular plugging, our understanding of epidermal changes associated with acne vulgaris development is continually growing.

• Research support for epidermal barrier dysfunction is now adding a unique element to our understanding of the processes underlying acne development.

• In this context, the barrier functions for both the epidermis of exposed skin, as well as that of the follicular epithelial lining, are potentially involved in acne vulgaris pathophysiology and/or impairment in water flow and epidermal hydration.

Levin J. The Relationship of Proper Skin Cleansing to Pathophysiology, Clinical Benefits, and the Concomitant Use of Prescription Topical Therapies in Patients with Acne Vulgaris. Dermatol Clin (2016) 34; 133–145


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Ceramides in Acne: Lines of Evidence

• Reduced total ceramide content…Acne patients are found to have significantly reduced free sphingosine and total amounts of ceramides in their stratum corneum; this reduction correlates with acne severity

• Regarding that reduced sphingosine…The reduction in sphingosine, in particular phytosphingosine, is also believed to contribute toward skin inflammation and infection associated with acne vulgaris

• As discussed earlier, phytosphingosine shows evidence of both anti-microbial & anti-inflammatory effects, with some evidence from a 2-month pilot study demonstrating an 89% reduction in acne papules and pustules with use of topical 0.2% Phytosphingosine

• Increased TEWL…In addition to increased sebum production and sebaceous gland size, those with acne exhibit a marked increase in Trans Epidermal Water Loss (TEWL - a measure of barrier integrity) and reduced stratum corneum hydration. This finding exhibits a positive correlation with acne severity

• Contribution to comedo formation…as barrier dysfunction is accompanied by hyperkeratosis of the follicular epithelium

• Impact of inflammation…The presence and intensity of inflammation may further impact the epidermal & follicular epidermal barrier integrity

• What irony!...Standard treatments for acne may ironically further impact epidermal barrier functioning (further highlighting the benefit of combining these therapies with barrier supportive measures):

• Benzoyl peroxide: Can increase TEWL and reduce epidermal antioxidant (tocopherol) content• Topical Retinoids: Impact on barrier likely due to increased corneocyte desquamation and reduced stratum

corneum thickness; concurrent use of barrier-supportive moisturizer reduces barrier impairment and may also reduce sign & symptoms of retinoid dermatitis when initiating therapy, without any loss of treatment efficacy


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Key findings from a consensus paper summarized by a Dermatological research panel determined the following:

• A common reason for non-compliance with standard acne treatment is dry skin and irritation, including topical treatments and systemic retinoids

• Skin barrier dysfunction may contribute to the signs and symptoms of acne• Moisturizers can improve acne-treatment related dryness and irritation• Ceramide-containing moisturizer, in particular, may improve adherence and complement

prescribed acne treatments• Adjunctive therapy with moisturizers, including ceramide-containing, should be considered

in all acne patients

• Lynde et al. Moisturizers and Ceramide-containing Moisturizers May Offer Concomitant Therapy with Benefits. J Clin Aesthet Dermatol. 2014;7(3): 18-26



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All images: Lynde et al. Moisturizers and Ceramide-containing Moisturizers May Offer Concomitant Therapy with Benefits. J Clin Aesthet Dermatol. 2014;7(3): 18-26


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Beyond moisturizer, the use of ceramide cleanser and delivery technology…

• Research studies have also used a combination of a ceramide-based cleanser and moisturizer for acne and other skin concerns, for example…

• The study…A 12 week open-label trial of 20 patients with mild-moderate acne incorporated the combination of both a ceramide-based cleanser and ceramide-based moisturizer (twice daily use, applied ahead of treatment topical) in conjunction with conventional topical therapies, specifically, clindamycin phosphate (1.2%, AM use), benzoyl peroxide (2.5%, AM use), and micronized tretinoin (0.05%, PM use). Endpoints evaluated were for efficacy in treatment and tolerability measures.

• The Results…• Efficacy: The primary endpoint was to determine treatment success based on changes seen from

a 6-point Physical Global Assessment scale used: (Baseline) Clear Almost ClearMild (13 subjects) Moderate (7 subjects) Severe Very Severe

• At the 12 week mark, 60% of subjects were assessed as ‘Clear’ to ‘Almost Clear’ together these effects enhanced overall treatment efficacy

• Tolerability: A four point scale was used to determine presence/severity of adverse effects from the acne medications (0=none, 1=mild, 2=moderate, 3=severe), including erythema, dryness, scaling, burning/stinging

• Overall, score improvement from baseline was noted for each of these parameters by Week 12 (see side)

• And thus…Together, the addition of the ceramide cleanser and moisturizer suggest an improvement in topical medicine tolerability and efficacy (authors cited, and compared, efficacy rates from pooled data regarding the topical medications above as monotherapy)

• Unique delivery tech…• Another unique aspect of this study was the delivery technology of the ceramide products, such

that they were configured into a time-released multilamellar vesicular emulsion (MVE). • This allows the ceramides, and other moisturizing ingredients, to more gradually be released onto

the skin for a period of time after application• Zeichner JA & Del Rosso JQ. Multivesicular Emulsion Ceramide-containing Moisturizers: An

Evaluation of Their Role in the Management of Common Skin Disorders. J Clin Aesthet Dermatol. 2016; 9(12):26–32

Above images from: Zeichner, J.A. et al. Efficacy and safety of a ceramide containing moisturizer followed by fixed-dose clindamycin phosphate 1.2%/Benzoyl peroxide 2.5% gel in the morning in combination with a ceramide containing moisturizer followed by tretinoin 0.05% gel in the evening for the treatment of facial acne vulgaris. J Drugs Dermatol. 2012; 11(6): 748-752


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KEY COSMECEUTICALS IN ACNE:PRODUCT TYPES

Cleansers• General role/use: Remove sweat, sebum, bacteria, debris,

secretions, while supporting the exfoliation of the stratum corneum• Contain surfactants which lift and remove dirt and oil, however

they can also be harsh/irritating to the lipids in the SC since they cannot distinguish between matrix lipids and unwanted facial/body sebum. This can lead to barrier damage and dry skin

• Resist the temptation!...Many with oily skin may want to use a strong detergent (soap) cleanser, however this puts them at risk for the above mentioned barrier damage and skin dryness

• Goal in acne: to strike a balance between removing enough sebum to reduce oily facial shine, yet do so without inducing temporary skin dehydration

• Newer cleansers are designed to minimize the above barrier damage…


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Soaps (aka ‘true soaps’)• Earliest form of skin cleanser• Alkaline pH and more harsh to skin barrier lipids• Leaves skin less soft and more irritated vs syndets…especially for patients

managing eczema, acne, rosacea; or cosmetically, if using topical retinoids or after a chemical peel

Syndets• Combines a mild surfactant with a moisturizing lotion containing

humectant, occlusive, and/or emollient ingredients • More efficient at remoisturizing/protecting the SC barrier vs soaps…

Thus, a better choice for Px managing the above listed concerns• Neutral/Acidic pH‘Combars’ • Combine ingredients of both soap bars and syndet cleansers • Will remove more matrix lipids due to presence of soapOil-free cleansers • Among the gentlest on skin • Like syndets, they are neutral/acidic in pH, leave behind a thin layer of

moisturization, and typically are formulated with little to no fragrances, dyes or irritating preservatives Talakoub, L. et al. (2009). Cosmeceuticals. In Murad,

A. et al (Eds), Cosmetic Dermatology, Elsevier p.7-34


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TAKE HOME MESSAGE: Direct your patients toward the use of lipid-free and syndet cleansers• Concern over ‘harsh’ cleansers (soaps, combars, or any cleanser with alkaline pH): Although

very effective in surfactant action of removing excess sebum and debris, main concerns as a cleansing agent for acne vulgaris include:

• Stripping away and/or damage to the Stratum Corneum lipid matrix and protein structures, contributing to:

• Reduced barrier function and associated increase in TEWL• Increase in penetration of topical substances, potentially increasing the chance for skin irritation and sensitivity

• Increase in skin pH (more on this later)• Alteration of the skin’s bacterial flora (yup, more on this later too!)• Skin dehydration• Erythema and irritation• Ironically, an increase in follicular plugging(!)

• The role/benefit of syndets and lipid-free cleansers: Due to their extremely low (syndets) to no (lipid-free) content of soap constituents, and a lower pH, these products should be encouraged for use in this population. Other benefits include:

• Minimal stripping of skin barrier lipids and proteins, thus less irritating and drying• Leave behind a moisturizing film• Lipid-free cleansers are typically devoid of dyes, fragrances and irritating preservatives• Proven efficacy in the management of irritation and inflammation-prone conditions such as rosacea,

atopic dermatitis, and acne


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Goals of cleansing in acne patients…• Most/all of these are typically satisfied by syndet and oil-free cleansers• However…• Even within these skin-friendly cleanser categories, variations exist regarding:

• pH of the cleanser• Degree of hydration/dehydration caused by cleansing• Degree of the surfactant’s interaction with skin proteins and lipids • If the final product itself (vs only the data from individual formula ingredients)

underwent sensitivity and/or comedogenicity testing• As such…

• It is always recommended to ensure these products have been tested, and shown to be effective and tolerated, in populations managing these types of dermatological concerns.

• This can be achieved via exploring studies reviewing specific brand products and/or contacting product companies to confirm and, if desired, obtain such testing by the company itself

To Foam or not to foam?...Some sources recommend use of foaming cleansers to enhance the removal of excess sebum/lipids on oily skin; while drier skin types will benefit from non-foaming oil-free or syndet cleansers



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QUICK LOOK: ASSESSMENT & FREQUENCY OF CLEANSING IN ACNE

Assessment and review of your patients’ cleansing regimen is an integral part of aesthetic care Review should include: • Frequency of facial cleansing• Cleansing products used • Other topicals used in the management of acne (daily or on as

needed basis for pimple management)Research on cleansing frequency: • Although further study is still needed, early research has shown

that cleansing twice daily is more effective than once daily, and that four times daily is no more effective than twice daily.

• The avoidance of over-cleansing/washing the face is especially important now that we know the negative effects it may impart regarding stratum corneum barrier disruption, including:

• Excessive water exposure (hot water in particular), leading to dehydration, irritation, changes in skin pH, and skin flora alteration

• But it’s more than just the frequency only…the beneficial effects of cleansing are likely just as much related to the type of cleanser used (as we saw), and potentially cosmeceutical ingredients added to the cleanser (as we’ll see), than it is the actual frequency of washing


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Specialty Cleansing Products:

• Cleansing/Exfoliating scrubs (aka ‘scrubs’)• Combine surfactants with aluminum oxide, ground fruit pits, polyethylene beads,

or sodium tetraborate decahydrate granules to create a suspension formula• The particles are manually massaged into the skin, helping to dislodge

desquamating corneocytes and improve skin visual smoothness and tactile softness. Improved luminosity and skin radiance are also noted

• Typically, the scrub is used once weekly (unless designed for more frequent use); however, more frequent or aggressive use can cause skin barrier damage and skin sensitivity

• Aluminum oxide and ground fruit pits produce more aggressive exfoliation due to their rough surface contour; however, fine powders of both ground apricot pit powder and walnut shell have been introduced, producing less skin trauma

• Polyethylene beads are smooth and roll when rubbed over the skin surface, creating a milder exfoliation with little potential for skin damage. However, they may have an environmental side-effect…



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• Cleansing Cloths• Another cosmeceutical product where cleansing and

physical/chemical exfoliation are combined• The surfactant is impregnated in the cloth, which can be either

wet or dry• Premoistened cloths are simply rubbed over the face followed by

water rinsing, whereas the dry cloths are moistened with water prior to use

• The cloths are single use and manufactured from polyester, rayon, cotton, and cellulose fibers, and are formed into a thin sheet

• Further cleansing attributes are imparted via texturing the cloth with either an open or closed weave

• Open-weave cloths contain 2-mm to 3-mm windows in-between adjacent fiber bundles. This provides the effect of a more mild degree of exfoliation

• Closed-weave cloths, by contrast, have a tighter weave, provide a stronger exfoliant effect, and are designed to maximize the removal of sebum, cosmetics, and dirt.

• Taken together, the degree of exfoliation and cleansing will depend on cloth weave, cleansing pressure, and length of cloth cleansing time

• Cleansing cloths can be adapted for various skin types, including for normal to oily skin, normal to dry skin, or sensitive skin. This is accomplished by variations in surfactant strength, and altering the weave toward more/less exfoliation ability (ex. higher for the normal-oily skin cloths, etc.)


Draelos, Z. Cosmeceuticals: what’s real, what’s not. Dermatol Clin 37 (2019) 107–115


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• Medicated Cleansers• Typically include benzoyl peroxide (up to 10%) or salicylic acid (up to 2%)• In short…benzoyl peroxide possesses antibacterial and comedolytic benefits, while

also limiting the development of resistant acne organisms when it is used in a cleanser form

• What about our friend from the Willow tree?...• Salicylic acid is able to penetrate into the follicle to assist in dislodging the comedonal plug

from its follicular lining; however, more research is needed to confirm its effectiveness in a cleanser format…

• That’s because…The short length time frame of skin contact when used as a cleanser has called into question its ability to fully impart its known benefits

• Additionally, salicylic acid does not kill Propionibacterium acnes and does not prevent the development of antibiotic resistance

• Despite this, some research shows that a 2% salicylic acid scrub results in a reduction of open comedones

• The benefit of being OTC…One benefit of incorporating monographed acne ingredients into a cosmetically elegant OTC form (at least as compared to the standard prescription drugs format) might be an increase in compliance, consumer acceptance, and thus effectiveness



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A QUICK REVIEW• Common Myths around cosmeceuticals & acne• Ceramides in Acne: The Growing Role of the Skin Barrier

• Reduced total ceramide content• Reduced sphingosine• Contribution to comedo formation• May improve adherence and complement prescribed acne

treatments• Cleansing in Acne

• Goals• True soap----Combar----Syndets----Oil-free cleansers• Frequency of twice daily • Cleansing product variety (washes, scrubs, cloths, medicated)


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Moisturizers & Serums• Occlusive Moisturizers

• Reduce TEWL by forming a hydrophobic film over the skin, in-between corneocytes

• More ‘greasy’ texture

• Humectant Moisturizers• Draws water both from the dermis below (especially in dry weather), and

air above, the epidermal SC• Glycerol, considered among the most effective humectants, also

functions to support desquamation by aiding in the lysis of corneocyte desmosomes

• In dry weather, best combined with occlusive moisturizer to prevent excessive dermal water loss and, ironically, skin dryness

• Emollient Moisturizers• Fill-in the crevices between desquamating corneocytes, creating an

instant moisturization with the feel of softer and smoother skin texture • Provide a degree of occlusive effects as well

• Moisturizing products will combine various physiologic (ex. ceramides, cholesterol, FFAs) and/or non-physiologic lipids (ex. petrolatum, lanolin, squalene), together with ingredients providing occlusive, humectant, and/or emollient effects

Serums: • Contain cosmeceutical ingredients in high concentration • Result in better skin penetration, and tend to stay on skin longer

(especially compared to cleanser as delivery system, given its short duration of contact time on the skin)

• Thicker in texture, thus a little goes a long way (often need only a few drops to cover the entire facial area)


Talakoub, L. et al. (2009). Cosmeceuticals. In Murad, A. et al (Eds), Cosmetic Dermatology, Elsevier p.7-34


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• Moisturizer/Serum Role in Acne Management: • Barrier support…At minimum, as a vehicle to provide barrier

support (physiologic lipids/ceramides); can complement ceramide-containing cleansers as we saw in acne research above

• ‘Come on and take a free ride’…• As a vehicle to provide/deliver therapeutic and appearance-altering

cosmeceuticals (seen box on the right)• Many of these apply to acne (anti-inflammatories, retinol, physiologic

lipids, skin lighteners for preventing post-inflammatory hyperpigmentation, etc.):

• To reduce any areas of skin dryness if managing combination of oily and dry areas of skin

• Some sources feel that moisturizers are not always needed over very oily areas of skin (however barrier supportive ceramides should still be obtained via other products used, such as cleansers or, more recently, toners/micellar water and cleansing cloths)

• To tolerate the intolerable…To offset any flaking/irritation/tolerability concerns which can accompany standard treatment like topical Vitamin A therapy

• Don’t Forget the Match game…Any moisturizer used should be matched to skin type (ex. suitable for oily-normal/dry-normal/etc. if using standard skin typing, or matched to appropriate Baumann skin type if using that skin typing system)


Draelos, Z. Cosmeceuticals: what’s real, what’s not. Dermatol Clin 37 (2019) 107–115


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Quick Look: Basics of moisturizer construction: • Moisturizers tend to be formulated into:

• Lotions (an oil-in-water emulsion, containing a higher amount of water relative to oil), or

• Creams (water-in-oil emulsions, higher in oil relative to water)• From here, manufacturers can adjust the oil:water ratio, as well as the

‘heaviness’ of occlusive/emollient moisturizing ingredients used… • For managing oily skin…

• In an ‘oil-free’ facial moisturizer marketed toward those managing oily and acne-prone skin, dimethicone and cyclomethicone may be used owing to their properties of being non-greasy and non-acne forming

• Talc or kaolin may also be added to the formula given their oil/sebum-absorbing properties and to help reduce the appearance of facial ‘shine’

• Or dry skin…• By contrast, dry skin may benefit more from formulas with a higher oil-

to-water ratio (such as creams), and ‘heavier’ moisturizers like petrolatum or mineral oil



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Toners, Masks & Oil-AbsorbersToners• Typically used after cleansing as a means of further removing any sebum,

make-up, etc. which was incompletely removed by the cleanser• T-zone relief…In combination oily-dry skin, often applied over oily T-zone

(forehead, between eyebrows and over the nose and chin), sparing drier skin areas (esp. with an alcohol-based toner which can further damage the skin barrier in those areas)

• Are alcohol (higher alcohol content for oily skin-marketed toners; lower levels for normal skin) or non-alcohol based (for dry skin, typically contain propylene glycol and water)

• Adaptable…Formulation can be adapted according to cosmetic goal:• Acne use (to contain salicylic acid, tea tree oil, and high tannin content)• Dry skin (to contain honey, allantoin, and aloe vera)

• Widely used owing to the tactile and aesthetically-pleasing effects they provide • Generally seen as an optionally-used cosmeceutical…it may not be necessary

if an efficient cleanser is already being used• One product, many names…Inconsistent nomenclature leads to confusion, as

toners are also referred to as astringents, skin fresheners, toning lotions, clarifying lotions, or pore lotions


Never let a newbie buy your toner for you!!


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Masks

• Originally inspired, and derived from, the practice of mud baths; with some sources citing historical use in Ayurvedic, Ancient Egyptian and Roman traditions

• Made from… • Polyvinyl alcohol (allowing them to be peeled off)• Clay-based (which will dry onto the skin and be rinsed off)

• Used for… • Chemical or mechanical exfoliation • Skin hydration• Unclogging pores• As a vehicle to provide a cosmeceutical/therapeutic agent to the skin

• Multifaceted…Like toners, ingredients added can be tailored according to use:

• Acne-focused masks (to contain salicylic acid or sulfur)• Skin soothing use for inflammatory skin (ex. rosacea) (to contain honey or

green tea) • General use (to contain honey, algae, cucumber, essential oils, or soy)

• Typically are used weekly



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• Oil-control Products and Ingredients• Include Talc (talcum powder), kaolin clay, bamboo powder, polymer beads, among other

cosmeceutical actives (see oil-reducing chart later in course) embedded into ‘oil-absorbing’ cosmetics/makeup, moisturizers, sunscreens, and ‘blotting’ papers

• Targeted toward removing oil from skin surface, without a direct effect on oil/sebum production in of itself (although some cosmeceutical reviewed later show potential for also influencing sebum production)

• Aesthetically are used to reduce facial ‘shine’• Blotting papers…

• Thin sheets of paper that resemble tissue paper and are easily portable • They are pressed into any oily areas of the face, such as the T-zone, to absorb excess oil onto the

paper and decrease facial shine• Are recommended to be pressed, not rubbed, since rubbing will remove any facial cosmetics. • Very effective at removing facial shine

• In selecting makeup, have your Px consider use of: • Oil-free/powdered foundation, pressed facial powder, powdered eyeshadow, blush, which will all

help absorb oil and last longer. The newer, all-in-one BB Cream products can also be considered• Some of these may also contain SPF (if using powdered products, for optimal protection they are

best to use overtop previously applied sunscreen)



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Spot Treatment for Active Comedones

• As we’ve all likely heard, it is best to leave a pimple alone…despite the unbelievable urge that exists to pop it!!• Typical spot-treatments…tend to contain either salicylic acid or benzoyl peroxide• But to make things unique…Brand-name spot-treatment products will then distinguish themselves by also

including in their product any of the following: • Makeup concealer for a 2-in-1 cover-up effect• Witch Hazel for its astringency• Cosmeceuticals known to have an actual or theoretical benefit in long-term acne management (many of these

we will review next): sulfur, glycolic acid, oregano oil, allantoin, licorice extract, charcoal, aloe, prebiotic and probiotics

• Patented ingredients/ingredient combinations, or ‘technologies’, purported to have a complementary effect with salicylic acid/benzoyl peroxide

• They may also offer their products in various vehicles: Lotions, toners, gels, Treatment Pads/wipes, and, yet again, patented ‘technologies’ such as encapsulation methods to promote the sustained-release of the active ingredient at the site of application

• I say popular topical botanical for acne, you say…Tea Tree oil • Some companies market tea tree oil-focused ‘on-the-spot’ acne formulations, with a minimal concentration of at

least 5%• Theoretical basis for ‘on-the-spot’ use is tied into it’s researched anti-microbial (including against P.acnes) and

anti-inflammatory activity• Most research however has evaluated tea tree oil use over a longer duration, typically for at least 4 weeks• Some evidence shown less irritation and better tolerability as compared to benzoyl peroxide



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QUICK LOOK: SKIN pH & ACNE• pH = ‘potential hydrogen’…the acid-alkaline ratio of a substance ranging from 0 (most acidic) to

14 (most alkaline)• The body gradient…Skin pH is normally acidic (4-6), while internally the body maintains a

neutral/slight alkaline pH of around 7.4; thus a steep gradient of 2-3 units exists between the stratum corneum and internal milieu; Interestingly, pH has been found to increase even with each deeper layer of corneocytes!

• The ‘Acid Mantle’…• Describes the acidic nature of the skin surface as a whole• Created and maintained by various mechanisms:

• Lactic acid from eccrine sweat gland secretion• Proton-donating free fatty acids generated via the bulk hydrolysis of epidermal phospholipids in the late

stages of epidermal differentiation• Lipase activity of resident bacteria and sebaceous glands leads to free fatty acid production and

accumulation on the skin surface• Histidine metabolism-based generation of urocanic acid


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pH & Acne Connections…• An acidic stratum corneum pH is essential for the functioning of the skin barrier system; shifts

in the skin pH have been found to predispose to various inflammatory and infectious skin concerns, including acne

• Lipid matrix formation is acid-dependent: • Ceramide synthesis enzymes, glucocerebrosidase and sphingomyelinase are both (low) pH-

dependent• Lamellar body formation and processing in the epidermis requires an acidic environment• A transient increase in pH can activate serine proteases involved in natural epidermal

desquamation; if sustained, this can inhibit lamellar body secretion (limiting lipid matrix formation) while stimulating epidermal hyperproliferation

• pH and bacterial flora: increased skin pH leads to increases in the population and activity of P.acnes, and other microbes, possibly owing to the reduced action of antimicrobial peptides

• pH and sebum: Acne-associated sebum secretion carries a lower free fatty acid content, potentially lowering its contribution to the acid mantle formation

• pH and hormones: Androgens can inhibit lamellar body formation and secretion into the extracellular space, and have been found to negatively impact barrier repair/recovery; such an effect on lamellar bodies can also interfere with its contribution to acid mantle formation

• Role in Sensitive Skin?...Skin that is regularly at a higher pH can more easily be irritated by skincare ingredients with a known irritative profile, such as sodium lauryl sulfate

QUICK LOOK: SKIN pH & ACNE


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• Goal in Acne: Acidify the Stratum Corneum!...• Evidence suggests that lowering skin pH reduces the TH2 inflammatory response and speeds barrier function recovery, thus

preventing epidermal hyperproliferation• Regular cleansing via the use of a syndet bar (acidifying) prior to acne lesion development led to a reduction in skin irritation and

inflammatory acne lesions as compared to those using a soap (alkaline) cleanser • Regular use of syndets help maintain lower skin surface pH and Propionibacterial counts compared to neutral cleansers• One method topical antibiotics are believed to improve acne is via a reduction in skin surface pH

• Influencing the Acid Mantle…• Non-modifiable factors: Skin pigmentation (pigmented skin maintains a lower pH); Age (newborns skin is neutral pH, with acidification

transitioning gradually through the first year of life; adults are acidic; elderly move back toward a neutral pH)• Modifiable factors to consider for your patients:

• Cleansers…• Syndets and Lipid-free cleansers are key to maintaining an acidic skin surface• Impact on skin pH is both short-term (lasting for 2 hours immediately post-washing), and long-term (with use of 2 washings per day for at least 1

minute each)• The change in skin pH is directly proportional to the pH of the cleanser

• Moisturizers…• Recent research is now pointing to the role that moisturizers, and in particular those containing acidic-formulated emollient-based moisturizing

ingredients, can play in further acidifying the Stratum Corneum after skin cleansing

• Tap water only? Don’t go there!...• Using plain tap water without any cleansers can be problematic. It typically has a pH around 8, and can temporarily increase skin pH for up to 6

hours • Nutritional associations…Small preliminary reports indicate that reduced skin pH has been associated with dietary intake of:

• Vitamin A; Calcium; Monounsaturated fatty acids; Regular fluid intake; and diets rich in Histidine (owing to urocanic acid production described earlier; histidine rich foods include all animal and seafood products, including whey protein; and from plant sources, legumes, nuts, seeds, vegetables such as cauliflower, corn; fruit such as banana citrus fruit, and cantaloupe; and whole grain wheat, oat, barley, rice, and buckwheat)

QUICK LOOK: SKIN pH & ACNE

TAKE HOME MESSAGE: Moisturizers and cleansers should be formulated with a pH of no greater than 6; and ideally under 5


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Traditional & Established Cosmeceuticals & Medications1.Vitamin A Derivatives:• Why it’s so effective and popular…

• Primary benefit against comedo formation owing to its ability to interfere with the development of its precursor, the microcomedo

• Mechanisms include: • Reversal of abnormal keratinocyte desquamation• Anti-inflammatory effects (including the downregulation of Toll-

like receptors and inhibiting downstream inflammatory transcription factors)

• Alteration in cellular cohesiveness • Anti-seborrheic effects• Modulation of proliferation and differentiation.

• Taken together, the normalization of differentiation and proliferation of the follicular epithelium leads to the loosening and unseating of microcomedones, thereby preventing obstruction of the pilosebaceous unit

• Although prescription topical Retinoids such as Tretinoin, Tazarotene, and Adapalene are well-established mainstays in the treatment of acne vulgaris, there is a growing interest in the role that OTC/Cosmeceutical forms (and strengths) of Vitamin A can play.

KEY COSMECEUTICALS IN ACNE:PRODUCT INGREDIENTS

Saurat J. & Sorg, O. Retinoids. In Dermatology, 4th ed., edited by Bolognia, JL, Schaffer, JV., & Cerroni, L. 126, 2200-2214. Elsevier, 2018


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• Any room for an OTC/Cosmeceutical market?...• The reduced efficacy of OTCs in relation to their

prescription counterparts is well-established, especially for severe forms of acne

• However, for mild-moderate forms, OTC/Cosmeceutical formulations have gained in popularity

• The ability of the cutaneous enzymatic processes needed to convert retinol into the all trans-retinoic acid (tretinoin) is the rate-limiting factor. Small amounts of OTC retinoids (ex. retinol, retinaldehyde) are converted to all-trans retinoic acid in the dermis

• Further exploration is warranted to help delineate the role and benefit of OTCs in acne management and prevention

• A new OTC option (for my American colleagues)….• Interestingly, Adapalene (0.1%) has recently moved

into the OTC market in the United States• Its lipophilic properties are believed to contribute

toward improved pilosebaceous uptake and anti-acne activity

• While adapalene affects the cellular differentiation, keratinization, and inflammatory processes that are abnormal in acne, it has no sebostatic effect

• Its irritancy profile is decreased as compared to tretinoin.


Draelos Z.D. (2016). Acne. In Draelos Z.D. et al (Eds.), Cosmeceuticals, 3rd ed Elsevier (p. 179-180)


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• Tolerance concerns…• Skin irritancy and questions surrounding teratogenicity are

factors patients may ask about• Although the concern over teratogenicity lies primarily for

oral use of supplemental/prescription retinoids, some medical sources even extend this avoidance of OTC/Rx topical retinoid treatment to any patient who is/may become pregnant (and nursing)

• Regarding skin irritancy for OTC cosmeceutical retinoids, the retinol form (up to 1%) generally carries the highest irritancy profile as compared to other cosmeceutical retinoid forms, such as retinaldehyde (0.05%), and retinyl esters (ex. retinyl palmitate, 2%)


Saurat J. & Sorg, O. Retinoids. In Dermatology, 4th ed., edited by Bolognia, JL, Schaffer, JV., & Cerroni, L. 126, 2200-2214. Elsevier, 2018

From: Baumann L & Weisberg E. (2018). Skincare and Nonsurgical Skin Rejuvenation. In Rubin J.P. & Neligan P.C. (Eds.),Plastic Surgery: Volume 2: Aesthetics Surgery, 4th ed. Elsevier. (p. 23-37)


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2. Salicylic acid:• An oil-soluble beta-hydroxy acid, derived originally from (as we

all know), botanical sources of salicin, such as willow bark• ‘Oil-solubility’ is the key…this allows it to penetrate into the

sebum-rich milieu of the pore, within which it is able to loosen and dislodge the comedonal plug from the follicular lining

• Since it’s there…may exert some low level anti-inflammatory effects (double benefit!).

• Versatile…it can easily be incorporated into cleansers, moisturizers, facial foundations, and other cosmeceutical formulations. Concentration strengths of up to 2% are typically used

• Its ability to induce exfoliation has also allowed salicylic acid to function as an antiaging/acne ingredient for men and women with both needs.

• Any Achilles-heel?... • Salicylic acid does not kill Propionibacterium acnes and does

not prevent the development of antibiotic resistance. • As such, salicylic acid may be less effective than benzoyl

peroxide in acne treatment, but it is also less irritating and less allergenic.



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3. Benzoyl peroxide (BPO)• A potent bactericidal agent that reduces P. acnes within the follicle• Mild comedolytic properties, particularly effective when combined with other

therapies• In contrast to topical antibiotics, microbial resistance to benzoyl peroxide has not

been reported.• Many forms available…

• Preparations for all skin types are available in both OTC and prescription formulations • Examples include bar soaps, washes, gels, lotions, creams, foams, and cosmetic pads • Also available combined with clindamycin, erythromycin, or adapalene

• Concentrations range from 2.5% to 10% • Can produce contact dermatitis…more often of irritant form (vs allergic)• As we saw…Traditionally a first line Tx for moderate-severe acne, and in those with

mild acne exhibiting papular/pustular lesions



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4. Tea tree oil:• The most common herbal essential oil used in the treatment of acne • Derived from the Australian tree Melaleuca alternifolia• Variety of anti-microbial properties: antiseptic, antifungal, and antibacterial• Popular in the marketplace…Added to a wide range of cosmetic products, some for therapeutic value and

some for marketing appeal, including: soap bars, cleansers, body wash, toners, spot treatment gels or sticks, and masks. Can also be in combination with other acne treatment agent such as benzoyl peroxide, salicylic acid, glycolic acid or azelaic acid

• Takeaways from a recent review article exploring evidence-based treatment effects of tea tree oil:• Use of products containing at least 5% tea tree oil, with twice daily application, led to a significant reduction in

acne lesion numbers lesion numbers when used for 4–8 weeks. • Comparative trials showed that tea tree oil products were better than placebo and equivalent to comparison

products, these included 5% benzoyl peroxide and 2% topical erythromycin• Most studies explored the use of tea tree oil in those with mild-to-moderate acne severity, however preliminary

evidence from another study in those with nodular and cystic acne lesions showed minor improvement after 4 weeks of use

• The authors did highlight a potential limitation of the studies they reviewed. Although most were randomized design, they may have been hindered by inadequate blinding

• When used in low concentration topically for the treatment of acne, tea tree oil has not produced any toxicity concerns. However, tea tree oil is a known cause of allergic contact dermatitis

• Hammer, K.A. Treatment of acne with tea tree oil (melaleuca) products: A review of efficacy, tolerability and potential modes of action. International Journal of Antimicrobial Agents 45 (2015) 106–110



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A clearer picture of its therapeutic effects:• Anti-bacterial activity:

• Tea tree oil is well-established in its anti-bacterial activity, including against P.acnes

• An interesting wrinkle (and why it may ‘take it’s time’ to treat)…Getting through the biofilm

• Anti-inflammatory activity• Inflammatory changes are noted in

acne-prone skin even prior to hyperproliferation and the formation of microcomedones

• These inflammatory changes are characterised by the CD4+ presence of T-helper cells and macrophages at levels above those found in skin not prone to acne.

• Acne lesions are also able to form in the absence of P. acnes, further supporting the critical role of inflammation in comedogenesis


Hammer, K.A. Treatment of acne with tea tree oil (melaleuca) products: A review of efficacy, tolerability and potential modes of action. International Journal of Antimicrobial Agents 45 (2015) 106–110


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5. Azelaic acid • A naturally occurring dicarboxylic acid found in cereal grains, and sourced from

Pityrosporum ovale • Available as a topical cream (up to 20%), shown to be effective in inflammatory and

comedonal acne• Reduces inflammatory acne by inhibiting the growth of P. acnes. • Comedolytic properties are attributed to the reversal of altered keratinization within follicles

affected by acne • Balance of effect?... activity of azelaic acid against inflammatory lesions is believed to be

greater than its activity against (non-inflammatory) comedones. • Azelaic acid is applied twice daily, and is reported to have fewer local side effects than

topical retinoids. • An added benefit for PIH…it may help to lighten post-inflammatory hyperpigmentation • Rx-only in some jurisdictions…check access if your have Rx rights in your state/province



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A QUICK REVIEW• Moisturizers and Serums

• Occlusive, Humectant, Emollient• Toners, masks and oil-absorbers• Spot-treatments for acne• Skin pH & acne• Popular cosmeceuticals

• Retinoids• Salicylic acid• Benzoyl peroxide• Tea tree oil• Azelaic acid


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Lesser-known & Emerging Cosmeceutical Ingredients1. Sulfur: • The oldest treatment of acne predating benzoyl peroxide and salicylic acid is sulfur• Has been used for centuries to treat various dermatologic conditions. Early medical texts

dating to the Roman era are said to describe the use of a sulfur mineral bath for the treatment of acne

• MOA…Sulfur’s mechanism of action is not fully elucidated, but is thought that sulphur interacts with cysteine in the stratum corneum, causing reduction of sulfur to hydrogen sulfide. In turn, hydrogen sulfide degrades keratin producing the keratolytic effect of sulfur

• Anti-microbial…• Elemental sulfur and its various forms (e.g., sulfides, sulfites, and mercaptans) possess antimicrobial

and antifungal properties in addition to acting as anti-inflammatory agents. • Sulfur is often combined with sodium sulfacetamide, a sulfonamide agent that exhibits

antibacterial properties. Sodium sulfacetamide has also been shown to be active against P. acnes. • The keratolytic and anti-inflammatory effects of sulfur (up to 10%) and the antibacterial

effect of sulfacetamide (up to 10%) in combination yield an effective topical formulation for the treatment of acne vulgaris, rosacea, and seborrheic dermatitis.

• For sulfacetamide products, caution in those with sulfa allergy…sulfacetamide-based products have been shown to induce life-threatening hypersensitivity reactions and thus should be avoided in patients with a sulfa allergy



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2. Niacinamide: • Topical niacinamide offers a wide diversity of cutaneous effects. This may be due to acting as a key substance in the

NADPH pathway responsible for the energy-producing machinery of every cell….• More specifically, niacinamide is a precursor for nicotinamide adenine dinucleotide (NAD) and the phosphorylated derivative

NADP • NAD provides a substrate for the nuclear enzyme poly-ADP-ribose polymerase (PARP-1), which plays a role in repairing

damage from genotoxic stresses, such as UV radiation• Ensuring adequate cellular energy, in addition to a properly functioning PARP-1, is essential for a number of skin conditions

• Overall, niacinamide is useful in acne management owing to a range of established and theoretical benefits. It has been studied for, and used in, cosmeceuticals designed to minimize acne inflammation

• Potential benefits specific for acne management include:• Barrier support and hydration…Promotes glucosylceramide, sphingomyelin, fatty acid, and cholesterol synthesis from in

vitro keratinocytes; also found to up-regulate keratinocyte expression of filaggrin• Sensitive skin support…topical application improved stinging score in patients with sensitive skin• Sebum control…Both the excretion rate of sebum, as well as the sebum levels found/collected on the skin surface

(sometimes referred to as ‘casual’ sebum level), were shown to be reduced with topical niacinamide.• Protective role…helps protect the natural barrier of the skin against infection and may have a bacteriostatic effect on P.

acnes• Exfoliation effect• Anti-inflammatory activity (multiple lines of evidence)…

• Decreases the in vitro secretion of interleukin-8, a cytokine secreted by keratinocytes in response to pathogens (including P. acnes), this leads to an inhibition of leukocyte chemotaxis, thus limiting the inflammatory response

• Niacinamide acts as a ligand for the peroxisome proliferator-activated receptor (PPAR), expressed on adult keratinocytes, Langerhans cells, and melanocytes. Various isotypes of the PPAR are noted for anti-inflammatory properties

• Inhibition of lysosomal enzyme release and mast cell degranulation



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• Takeaways from a recent research review exploring use of topical niacinamide on acne treatment: • What it reviewed…10 studies met inclusion criteria, 8 using topical niacinamide (4 as niacinamide-only topical,

4 as a combination product), and 2 using oral niacinamide (we will review these in the oral supplements section later in this course)

• What it showed…The series of studies show topical nicotinamide treatments to have a significant effect on reducing acne vulgaris, while being very well tolerated. The 8 studies exploring topical niacinamide demonstrated a significant reduction in acne lesions in comparison with the patient’s baseline acne or similar efficacy to topical Clindamycin therapy

• That topical nicotinamide reduced acne lesions similarly to topical clindamycin opens the door to further exploring whether niacinamide could potentially be used as a treatment alternative to clindamycin. Regarding a niacinamide/clindamycin combo, 2 of the topical studies showed that niacinamide did not demonstrate any further reduction in acne lesions when added to clindamycin treatment.

• Topical niacinamide used in the research was 4-5% concentration• Limitations…Authors highlighted certain collective limitations of the studies reviewed, including:

• Use of an adequate control group (especially for niacinamide combination topicals, as no niacinamide-only topical was used for comparison in those studies)

• Expanding comparisons of niacinamide with other standard-of-care acne treatments• Lengthening treatment end points (most studies ranged 6-8 weeks, authors recommended up to 12 for a

better comparison with clindamycin)• Objectifying outcome measures (although quantitative outcome measures were used, there was little

consistency in which specific measures used (number of lesions, scarring, etc.)



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Bissett, D.L. Common Cosmeceuticals. Clinics in Dermatology. 2009; 27: 435-445

Walocko, F.M. et al. The role of nicotinamide in acne treatment. Dermatologic Therapy. 2017;30(5)


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3. Vitamin C• A popular cosmetic ingredient, especially for photoaging

products; explored here owing to its anti-inflammatory and skin lightening effects

• Unsightly at first…Early formulations of L-ascorbic acid often turned an unsightly yellow as a result of the oxidation by-product dehydroascorbic acid produced upon exposure to air

• Then they got it right…• Cosmetic chemists needed to develop more stable, and

easier to formulate, derivatives• From this effort such versions were developed, including

ascorbyl-6-palmitate (A-6-P), ascorbyl tetraisopalmitate (ATIP), magnesium ascorbyl phosphate (MAP), and sodium ascorbyl phosphate (SAP)



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3. Vitamin C (con’t)• As an anti-inflammatory…

• In vitro studies with vitamin C demonstrate a significant decrease in the activation of the transcription factor NF-KB, responsible for the production of a number of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin IL-1, IL-6, and IL-8

• Multiple randomized, double-blind, vehicle-controlled studies using sodium ascorbyl phosphate (SAP, 5%) demonstrate benefits on acne management under a variety of conditions/formulations:

• For inflammatory lesions…A 12 week study on 50 subjects with inflammatory acne showed a significant reduction in total lesion count, and noted improvement in subject and clinician global assessment score, in the SAP group as compared to placebo

• As a combo therapy…A combination comparison study explored the effects of 5% SAP combined with 0.2% retinol, along with each individually, in managing inflammatory acne. Although both stand-alone treatments produced benefit at the 4 and 8-week marks, the combination of the SAP with retinol provided the greatest degree of improvement. This was attributed to multiple lines of treatment effect offered by the combination therapy

• Alongside peels for acne scarring…Acne scarring can be managed by the use of chemical peels, with glycolic acid being one of the most commonly used alpha-hydroxy acid agents. One study found that SAP 5% used daily in-between glycolic acid peels (50%, a concentration typically administered by a dermatologist), which were applied 1-3 times per month, led to a reported moderate-to-excellent improvement of acne scarring in 79% of subjects (vs. 44% in control group)

• As a skin lightening agent… • May help reduce occurrence of post-inflammatory hyperpigmentation at the spot of

previous acne lesions • It decreases tyrosinase synthesis and acts as a reducing agent for melanin and melanin

intermediates such as dopaquinone



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4. Green tea: • From the unfermented leaves of Camellia sinensis, rich source of polyphenol

antioxidants• The main polyphenol studied in acne treatment is epigallocatechin-3-

gallate (EGCG)

• Keynotes from a recent research review article:• 8 articles met criteria; 2 reviewing effects of green tea polyphenols on

sebum production, and 6 examining their effects on acne vulgaris management

• Example of sebum assessment study: • 10 healthy men age 24–40 years-old applied 3% topical green tea to

their cheeks for eight week • A sebumeter device was used to measure the sebum secretion amounts

at 1, 2, 3, 4, and 8 weeks • The 3% topical green tea led to a significant reduction in sebum

production during the 8 week study period; More specifically, sebum production was reduced by nearly 10% in week 1, and as much as 60% by week 8

• Mahmood, T. et al. Outcomes of 3% green tea emulsion on skin sebum production in male volunteers. Bosn. J. Basic Med. Sci. (2010)10(3), 260–264



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4. Green tea: (con’t)• Example of acne treatment study:

• Randomized split face trial design examining the effectiveness of 1% EGCG and 5% EGCG topicals compared to placebo vehicle (containing 3% ethanol) in reducing acne lesion count

• Results indicate that the reduction in Leeds score was significant for both the 1% EGCG and 5% EGCG groups. Specifically, after 8 weeks, both non-inflammatory lesions and inflammatory lesions were reduced significantly after use of 1% EGCG and 5% EGCG, as compared to baseline

• No major differenced were noted between the 1% and 5% topicals with respect to lesion reduction. Overall, both 1% and 5% EGCG were both effective in improving acne vulgaris without major side effects

• Overall…studies reviewed suggest that green tea polyphenols exert their effect on sebum production and acne through a variety of mechanisms, including anti-microbial (including against P.acnes), anti-lipogenic, and anti-inflammatory

• Saric, S. et al. Green Tea and Other Tea Polyphenols: Effects on Sebum Production and Acne Vulgaris. Antioxidants 2017, 6(2)


Yoon, J.Y. et al. Epigallocatechin-3-gallate improves acne in humans by modulating intracellular molecular targets and inhibiting P.acnes. J. Investig. Dermatol. (2013),133, 429–440


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Green Tea: (con’t)• Proposed Mechanisms of Action of green tea

polyphenols based on reviewed studies (Saric et al.):• Modulation of the M locus protein kinase-Sterol

regulatory element-binding protein 1 (MLPK-SREBP-1) signaling pathway, which leads to reduction in lipogenesis

• Increased apoptosis of the SEB-1 cell line of sebocytes

• A reduction in the mean colony forming units of P. acnes

• Reduced inflammation via reduced transcription of the nuclear factor-kB (NF-kB) pathway

• What to look for…Most studies used green tea lotion (2-3% concentration); with some studies alternatively using a specified EGCG concentration of 1-5%

Yoon, J.Y. et al. Epigallocatechin-3-gallate improves acne in humans by modulating intracellular molecular targets and inhibiting P.acnes. J. Investig. Dermatol. (2013),133, 429–440


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5. Aloe: • A small study from Iran looked to compare the effect of adding topical aloe vera (50%)

gel to standard tretinoin cream (0.05%) in treating mild-moderate acne. This was compared to the use of the tretinoin cream alone with a placebo cream.

• Both total lesion count (TLC) and acne severity index (ASI) were used to determine the efficacy of treatment:

• TLC was defined as comedones + papules + pustules• ASI was according to the formula: papules + (2 x pustules) + (comedones/4)• Global acne grading system (GAGS scale) was also used

• Overall results showed a statistically significant improvement in TLC, ASI, and reduction in lesion score (based on GAGS scale) for the aloe/tretinoin combination group over the tretinoin/placebo group. This included both inflammatory (papule/pustule) and non-inflammatory (comedones) lesions. Thus representing evidence of a potential synergistic effect between aloe and tretinoin

• Interestingly, the aloe/tretinoin group experienced less cutaneous side effects (owing to the tretinoin component) than the control group. In particular, reduced erythema and burning sensation were noted

• Who to thank…Inner gel components, such as inner gel, such as salicylates, magnesium lactate, bradykinin, thromboxane inhibitors, sterols and a beta-linked acetyl mannan (acemannan) are believed to contribute to the anti-inflammatory and wound-healing properties of aloe

• Hajheydari et al. Effect of Aloe vera topical gel combined with tretinoin in treatment of mild and moderate acne vulgaris: a randomized, double-blind, prospective trial. Journal of Dermatological Treatment (2014); 25: 123–129



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How to use the upcoming charts…• Within the realm of topicals for managing

acne vulgaris, there are groupings of cosmeceutical ingredients which you may recommend, or request your patients look for, to be included in skin care products they use

• These can be ingredients found in any one of their: cleanser, moisturizer, treatment product (in base of moisturizer/serum/gel/etc), cleansing cloths, toner, etc.

• The charts that follow will provide examples of such cosmeceutical active ingredients to consider when exploring acne-supportive topical products for your patients; comments/ideas will be discussed as well



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Cosmeceutical Effects/Comment

Niacinamide Reduces amount of skin-surface sebum

Salicylic acid Oil-soluble exfoliant able to enter sebum-rich pore

Witch hazel Tannin-containing astringent used to remove excess sebum from face; popular ingredient in toners

Papaya Papain proteolytic enzyme removes oil and desquamating corneocytes from skin surface

Soy Source of genistein; used for anti-androgen effect in reducing oil production

Retinol Anti-seborrheic effects; cosmeceutical form produce drying effect similar to Rx retinoids, but to a lesser degree

Green Tea Preliminary evidence of 3% topical green tea/1-5% EGCG in reducing sebum production

Oil-reducing makeup Facial powders and foundations which are oil-free, with some designed to help absorb oil owing to the addition of talc and/or kaolin; may also contain salicylic acid, minerals, and SPF Sun protection

KEY COSMECEUTICALS IN ACNE: PRODUCT INGREDIENTS

Adapted from: Draelos Z.D. (2016). Oily Skin. In Draelos Z.D. et al (Eds.), Cosmeceuticals, 3rd ed Elsevier (p. 173-174)

1. Cosmeceutical active ingredients in limiting excess oiliness/surface sebum


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Zinc Metalloproteases needed for healing of all skin lesions, including acne, require zinc for metalloenzyme synthesis; multiple studies of topical zinc acetate (1.2%) show a beneficial effect, especially when combined with topical erythromycin

Sandalwood essential oil Anti-inflammatory effects; Wound healing and anti-P.acnes properties; 0.5% sandalwood oil in formulation with 0.5% salicylic acid showed positive benefits in reducing total lesion (both inflammatory and non-inflammatory), in an 8-week open label study

Rosemary extract Animal research shows inhibition of P.acnes-induced inflammation via suppression of cytokine production; invitro evidence of ability to reduce Nuclear Factor kB activation

Korean citrus (essential oil) Citrus oils from Citrus obovoides and Citrus natsudaidai have shown antibacterial activity against P. acnes, and in particular, a lower P. acnes secretion of IL-8 and tumor necrosis factor αlpha

Echinacea species Anti-microbial activity against P.acnes; In cell culture models, demonstrates the ability to reverse the P. acnes-induced secretion of several pro-inflammatory cytokines, such as IL-6 and IL-8

Turmeric Strong historical use for cosmetic benefit; Research limited for use in acne; theoretical benefit owing to its anti-inflammatory, antioxidant, skin lightening, and wound healing benefits

Ginkgo biloba Theoretical based on anti-inflammatory effects of ginkgolide & bilobalide components

Any antioxidant sources (botanical, nutrient, etc.)

Theoretical/Plausible based on role in mitigating inflammation

Green tea, aloe, Vitamin C, Niacinamide, Azelaic acid, Tea tree oil, Vitamin A derivatives

As previously described earlier in course

KEY COSMECEUTICALS IN ACNE: PRODUCT INGREDIENTS2. Cosmeceutical active ingredients providing an anti-inflammatory action


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• 3. Cosmeceutical active ingredients for the prevention of post-inflammatory hyperpigmentation (at location of acne lesion)

• Who’s often affected?...Darker skin tones (Fitzpatrick phototype 4, 5, or 6) are at higher risk of PIH development• What to use…Can look for these ingredients in either daily cleansers/moisturizers and/or as needed in the form of

a distinct skin lightener product. • When to use…Skin lightener products are recommended to be used after cleansing and toning, but prior to

other recommended products. Begin use at the onset of skin darkening and use temporarily for a few weeks, or until post-lesion pigmentation has resolved.

• They can also be applied to long-standing post-acne lesion dark spots; generally, use over entire face is recommended to avoid ‘bull’s eye’ areas of discoloration, however do refer to product usage recommendations to verify if spot-treatment is possible


Cosmetic Formulation Side-Note:A wide variety of pigment lightening preparations have recently been brought to market, and represent unique combinations of multiple ingredients An example of this is a commercial formulation is based on:

Hydroxyphenoxy propionic acid: a non-toxic derivative of hydroquinone, which inhibits melanin production without affecting melanocyte viabilityEllagic acid: a natural phenolic antioxidant found in fruits and berries, added here for its anti-inflammatory effect Salicylic acid: added to act as a penetration enhancer, given its lipid solubility, while also exfoliating the skin to aid in the desquamation of pigment containing keratinocytes

More companies seem to be employing this approach of combining cosmeceutical ingredients, each contributing different mechanismsof action, to ultimately provide enhanced cosmeceutical efficacy


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Hydroquinone The ‘gold standard’ skin lightening agent, however riddled with debate; tyrosinase inhibitor; typically used at 2% (OTC) or 4% (Rx) concentrations; highly unstable, can rapidly oxidize and turn brown; can produce skin irritation/dermatitis and post-inflammatory hypopigmentation, and is known to be cytotoxic to melanocytes; often combined with retinoids and corticosteroids to improve efficacy and reduce side effects; reduced industry use has spurred search for nutrient and herbal-based skin lightening agents

Unfermented soy (may be labeled as derived from ‘fresh soy milk’)

Unfermented extract containing STI (Soybean Trypsin Inhibitor) & BBI (Bowmann-Birk Inhibitor) proteins inhibits activation of PAR-2 (Protease Activated Receptor-2), thus inhibiting the movement of melanin-containing melanosome from the melanocyte to the keratinocyte

Retinol/Retinoids Multiple modes of action (tyrosinase synthesis inhibition, reduce melanosome transfer to keratinocytes, increased desquamation of keratinocytes); irritation concern requires slow titration to higher strengths; weak skin lightening agent

Vitamin C As reviewed earlier; Interacts with copper ions at tyrosinase active site, decreases melanogenesis by reducing conversion of L-DOPA to L-DOPA-Quinone; Magnesium-L-ascorbic acid-2-phosphate is more stable form; weak skin lightening agent; 3-17% concentration typically used

Niacinamide As reviewed earlier; PAR-2 inhibitor, thus inhibits melanosome transfer from melanocyte to keratinocyte; well tolerated; weak lightening agent; 2-5% typically used

3. Cosmeceutical active ingredients for the prevention of post-inflammatory hyperpigmentation (at location of acne lesion) –con’t



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Azelaic Acid As reviewed earlier; derived from the fungus Pityrosporum ovale, providing tyrosinase inhibition; can slightly sting on application; stronger/effective skin lightener; up to 20% strength used in clinical studies on hyperpigmentation reduction

Kojic Acid Produced from a variety of fungi species; inhibits tyrosinase by chelating copper at the active site of the enzyme; typically found in 1-4% concentrations; may be mildly irritating and allergenic in some

Glycolic acid Sugar-sourced alpha-hydroxy acid which, like vitamin A, increases exfoliation of pigmented corneocytes as a means to lighten skin. Also acts as a penetration enhancer for other skin lightening ingredients in the cosmeceutical formula; OTC lightening formulations are typically mild (up to 10% OTC concentration), higher concentrations used professionally as part of chemical peels; higher concentrations can cause irritation and photosensitivity

Licorice extract Flavonoids sourced from licorice root, such as glabridin, liquiritin and isoliquiritin, inhibit tyrosinase and disperse melanin; well tolerated with no known cytotoxicity, has become a popular herbal lightening ingredient

Arbutin Sourced from leaves of bearberry shrub, pear, blueberry and cranberry plants; a glycosylated hydroquinone, it inhibits tyrosinase activity and melanosome maturation without melanotoxic effects. Higher concentrations are correlated with greater action, although paradoxical hyperpigmentation has been seen. Deoxyarbutin, a synthetic form, causes greater inhibition of tyrosinase; arbutin is typically used in combination with other skin lightening agents at a concentration of 1-3%)

3. Cosmeceutical active ingredients for the prevention of post-inflammatory hyperpigmentation (at location of acne lesion) – con’t



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Aloe Dual benefit: mucilage acts to create a protective coating over the skin (thus minimizing the effects of barrier damage), while it also provides anti-inflammatory (in effect, anti-redness) benefits as it is rich in choline salicylate

Chamomile (including it being a source of Bisabolol)

Anti-inflammatory component often used in anti-redness moisturizers

Allantoin (Sourced from Comfrey root, or synthetically derived from uric acid)

Can enhance the water-holding capacity of the extracellular matrix, improving barrier function; has anti-inflammatory properties; and used in sensitive skin/anti-redness products

Ginkgo biloba Reduce inflammation through anti-free radical and anti-lipoperoxidation effects

Green tea Reduces ultraviolet B-induced inflammation through its antioxidant function

Panthenol (Provitamin B5) Supports skin hydration, skin soothing effect, and prevents skin barrier damage

Argan oil Rich source of linoleic acid, key for barrier support via its role in the production of long chain ceramides; antioxidant content (including tocopherols) also exert an anti-inflammatory/anti-redness effects

• Ceramide-containing topicals• Niacinamide• Alpha-lipoic acid• N-Acetyl Cysteine• Vitamin C

In general: any cosmeceuticals which strengthen the skin barrier, may also help reduce facial redness: ceramide-based cosmeceuticals (best researched); niacinamide (supports ceramide production; anti-inflammatory); Alpha-lipoic acid & N-acetyl-cysteine (antioxidants with in vitro evidence of stimulating ceramide production); Vitamin C (evidence of increasing the synthesis of ceramide subspecies)


4. Cosmeceutical active ingredients managing acne-associated facial redness and skin sensitivity


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A QUICK REVIEW

• Lesser-known/Emerging Cosmeceuticals • Sulfur • Niacinamide• Vitamin C• Green tea• Aloe

• Cosmeceutical charts• Sebum management• Anti-inflammatory• Post-inflammatory hyperpigmentation• Erythema & skin sensitivity


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NOVEL ORAL SUPPLEMENTATION FOR ACNE• 1. Vitamin B3

• 2 studies included in Niacinamide review article discussed earlier explored oral B3 treatment• General findings showed improvements in acne lesions (see table)…• One study used a combination product containing nicotinamide, zinc, copper, and folic acid;

with the other study using a product containing niacinamide, azelaic acid, zinc, pyridoxine, copper and folic acid

• Both studies demonstrated a significant improvement in acne vulgaris compared to baseline• However…Specific contribution of Niacinamide component may have been muddied by the

presence of the other nutrients in the formulas

Walocko, F.M. et al. The role of nicotinamide in acne treatment. Dermatologic Therapy. 2017;30(5)


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• Niacin vs Niacinamide Study…• Another recent pilot study from China explored the effects of oral B3 in a head-to-head

comparison between two of its most popular forms: Niacin vs Niacinamide • Theorized benefit based on actions described earlier (including anti-inflammatory,

bacteriostatic (vs P.acnes), and anti-sebum activity)• 108 subjects completed the 3 month study (56 in niacin group; 52 in niacinamide group);

mild-to-severe cases included; use of oral isotretinoin, antibiotics, topical agents, or phototherapy were among the key exclusions

• Niacin dose: 2000mg per day in divided doses (gradual build-up over 9 days’ time; began with 100mg qid, by day 9 were using 500mg qid); all subjects counselled regarding the expected niacin flush, and related symptoms

• Niacinamide dose: 200mg tid • Both groups were also treated with folic acid (10mg, tid), vitamin B6 (20mg, tid), vitamin

B12 (50mcg, bid). A high-protein, low-fat, low-glycemic-load diet and drinking more water was recommended. Specific food types to avoid included milk, beef, fried foods, and alcohol

• Assessment included acne lesion counts (performed twice a month to evaluate changes in the number of inflammatory lesions (papules or pustules) on the face, back, chest, and back of neck), and the Investigator’s Global Assessment scale

NOVEL ORAL SUPPLEMENTATION FOR ACNE


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• Key findings: • Both groups showed a beneficial response, with the niacin group in particular demonstrating both a more

significant, and more rapid onset of, lesion-abating effects over niacinamide:• Regarding calculated % improvement in lesion counts: Over 80% improvement noted in niacin group after 12

weeks (vs 63% in niacinamide group)• Niacin group had a larger number of cases reported/qualified as being ‘Clear’ by the study’s end• Despite trend toward overall improvement, new inflammatory acne lesions were found to occur more often

in the niacinamide group during the trial• No changes were noted in either hematological or liver function assessments during the trail; the symptoms

of flushing became very mild/non-significant in most subjects in the niacin group after 4 weeks’ of use


Both images from: Jiang Hao, Li Chang-yi. High dose niacin in the treatment of acne vulgaris: a pilot study. Chinese Journal of Aesthetic Medicine. 2016,25(12):54-59


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2. Vitex• Has been shown to be effective in the treatment of

premenstrual acne• Whole fruit extract increases progesterone levels and

reduce estrogen levels via its acting upon follicle-stimulating hormone and luteinizing hormone levels in the pituitary gland

• In addition, it works to decrease high premenstrual prolactin levels via dopaminergic mechanisms

• The German Commission E has recommended an intake of 40 mg/day for the treatment of acne.



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3. Green Tea • Preliminary study from Taiwan with 80 women, 25-45 yoa, in the

management of moderate-to-severe acne• One group (n = 40) received 1500 mg decaffeinated green tea daily

(1 capsule of 500 mg, 30 min after meal, tid) for four weeks. The second group received cellulose capsules (placebo)

• A dermatologist (blinded) recorded both inflammatory and non-inflammatory lesion counts over the areas of the forehead, cheeks, nose, perioral area, chin, and entire face, both at baseline and at four weeks post-treatment.

• Key findings…• Significant decrease in the inflammatory lesion counts on the

nose, perioral area, and chin in the green tea group compared to placebo group

• No significant difference in lesion counts on forehead, cheek, or in the total lesion count between green tea and placebo groups

• Despite the finding that decaffeinated green tea supplement treatment led to a reduction in lesion counts over the nose, perioral area, and chin as compared to placebo, the placebo group itself had significant within group difference in lesion counts by study’s end


Lu, P.H.; Hsu, C.H. Does supplementation with green tea extract improve acne in post-adolescent women? A randomized, double-blind, and placebo-controlled clinical trial. Complement. Ther. Med. (2016)25, 159–163


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4. Zinc and Zinc-combination supplements• An essential micronutrient for the proper functioning of various bodily processes. Among

these, zinc appears to play a key role in a number of skin disorders• Role and potential benefit of zinc in acne vulgaris was first recognized in the 1970s when it

was noted how acne improved after its administration to zinc deficient patients with acrodermatitis enteropathica

• Despite the exact mechanism by which zinc exerts its effects to improve acne vulgaris is still being explored, current knowledge had suggested a variety of possible mechanisms at work, these include:

• Regulation of protein, lipid, and nucleic acid metabolism owing to its role as an essential cofactor in over 300 metalloenzymes and 2,000 transcription factors.

• Regulation of DNA and RNA polymerases, thymidine kinases, and ribonucleases, thus assisting in the maintenance of proper cell replication, immune activity, and wound repair

• Inflammatory regulation via the inhibition of IL-6 and TNF-alpha production• Anti-inflammatory activity via the inhibition of integrin and toll-like receptor expression by

keratinocytes; this relates to the P. acnes induction of cytokine production through a toll-like receptor-dependent pathway

• Direct inhibition of P. acnes proliferation• Inhibition of 5 alpha-reductase, blocking the conversion of testosterone to

dihydrotestosterone (DHT) and suppressing sebaceous gland activity; this relates to DHT playing a key role in the development of acne as it stimulates sebaceous gland activity



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Key findings from a recent research review article exploring oral Zinc therapy in acne vulgaris management:• 11 studies using oral zinc met criteria• What Zn they used…Zinc gluconate and Zinc sulphate were the primary forms used in the single-agent studies; also studied

were zinc combination supplements, such as the commercial formula we saw earlier when reviewing niacinamide; it contains niacinamide, zinc, azelaic acid, pyridoxine, copper, folic acid. (interestingly, the ‘Forte’ version of that product also contains quercetin and curcumin)

• Quantitative outcomes were measured in all studies, such as inflammatory and non-inflammatory lesion counts; most studies also included qualitative outcomes, such as the subjective opinions of both subjects and reviewer

• For the zinc-only research… 8 studies determined zinc therapy to be efficacious as a treatment for acne vulgaris. Of these, 5 found a statistically significant improvement when compared to control subjects.

• Authors highlighted how the use of single-agent (Zinc only) therapy was less well tolerated compared to combination supplements containing zinc. This isn’t surprizing given the high doses these single-agent studies used. GI side effects, primarily nausea, were often reported. By contrast, the zinc combination studies (total of 2 met criteria) showed a significant improvement in acne, while being much better tolerated.

• Doses used in studies…• Most acne studies have explored dosage ranges of 30-150mg daily of elemental zinc (as zinc gluconate or zinc sulfate) used for

up to three months duration• A trial of the combination products may be warranted ahead of high dose zinc for a few reasons. First, as mentioned, this dose

level can lead to adverse effects, including GI symptoms of nausea, vomiting, bloating, and diarrhea; metallic taste in mouth; and if used long term, may cause sideroblastic anemia as well as copper deficiency. As such, pairing zinc use with copper (for example, 2mg qd) may avert this concern. High doses are also not recommended during pregnancy or lactation.

• A trial of lower dose zinc may be a good place to start as some references have recommended the use of 20 mg per day of zinc in those 9-13 years of age; and 30mg per day in those over 13, for the management of acne.

• See table and reference for further details regarding the studies reviewed



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Both images from: Cervantes, J. et al. The role of zinc in the treatment of acne: A review of the literature. Dermatologic Therapy. 2018;31(1)


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QUICK LOOK: EMERGING ROLE OF THE SKIN MICROBIOME

• I’m familiar with the gut flora, but what is this skin microbiome stuff?...

• An estimated 1 million bacteria, with hundreds of distinct species, inhabit every square centimeter of skin

• Recent evidence is establishing a new paradigm for how microbes cause disease, where not only pathogens, but also imbalances in the commensal ecosystem, can cause skin pathology

• Recent advances in DNA amplification and sequencing technologies can now circumvent the culture steps and provide a more complete, unbiased views of skin microbiota and their genetic content, collectively this can be called the ‘microbiome’

Sanford, JA & Gallo, RL. Functions of the skin microbiota in health and disease. Seminars in Immunology 25 (2013) 370– 377


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• A role in our defense…• Evidence now indicates that, like the gut microbiota, the skin’s commensal microbes play

a key role in both educating and assisting the immune system • A healthy skin barrier consists of both immune surveillance and epidermal keratinocytes,

which produce antimicrobial peptides (AMPs) that contribute to innate immunity • Expression of these AMPs are up-regulated by the presence of Propionibacterium species

and other Gram positive bacteria • In addition to AMPs, sebocytes can produce antimicrobial free fatty acids by hydrolyzing

sebum triglycerides• The gut-brain-skin axis…Emerging evidence is linking GI health, including the influence

of oral probiotics, as well as mood/stress, to the health and well-being of our skin • The role of stress…

• Stress is known to alter the intestinal lining by, for example, promoting bacterial overgrowth and slowing transit time

• Some research indicates over half of acne vulgaris patients have marked alterations to their intestinal microflora. Constipation is reportedly more frequent in adolescents with acne, along with the finding of significant reductions in Lactobacillus & Bifidobacterium species in this population


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Probiotics in Acne…Possible MOAs:• Direct inhibition of P.acnes

• Certain naturally-residing probiotics, such as Streptococcus salivarius (oropharynx) and Lactococcus sp. HY 449, have shown P.acnes inhibitory activity through the production of anti-bacterial proteins

• Ceramide and phytosphingosine production• Streptococcus thermophiles, applied as a cream for 7 days, has been

shown to increase ceramide production both in vitro and in vivo • In addition to barrier support, the increase in the phytosphingosine

component of ceramides offers an alternate benefit, as we reviewed its exhibition of direct anti-microbial activity against P.acnes

• Hence, another benefit to having phytosphingosine as an ingredient in your recommended ceramide-containing cosmeceuticals


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Probiotics in Acne…Possible MOAs (con’t):• Multiple lines of immunomodulatory, anti-inflammatory, and sebum-

reducing effects:

• Strain K12 of S. salivarius inhibited production of the pro-inflammatory cytokine IL-8 in epithelial cells and keratinocytes

• Human skin cultures treated with L. paracasei NCC2461 showed inhibition of substance-P–induced skin inflammation (Substance P may amplify both inflammation and sebum production)

• Enterococcus fecalis lotion applied to the face for 8 weeks; a 50% reduction of inflammatory lesions was noted compared to placebo

• Topical use of Lactobacillus plantarum (5%), twice daily for 2 months, was shown to significantly reduce the size and associated erythema of acne lesions, as well as improve skin barrier integrity; study authors theorized these effects were owing to down-regulating the expression of molecules involved in skin inflammation, similar to those induced by P. acnes (see side image)

• Oral administration of L. reuteri in stressed animals demonstrated significantly lower rates of perifollicular inflammation than controls, theoretically limiting one of the early steps in acne lesion formation

• Lactobacillus-fermented skim milk demonstrated a four-fold lower level of Insulin-like growth factor 1 (IGF-1) formation compared to nonfermented skim milk.

• Further research speculates that, as a group, probiotics may reduce inflammation in acne through the decrease of both inflammatory cytokine release and recruitment of CD8 cells, as well as by activating regulatory T cells

Muizzuddin, N. et al. Physiological effect of a probiotic on skin J. Cosmet. Sci., 2012, 63, 385–395


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Probiotics in Acne…Possible MOAs (con’t):• As an adjunctive treatment to standard care

• In one small 12 week study, the combination of oral antibiotics (minocycline) with oral probiotics (See ‘Commercial product’ in box in the upcoming slide; 2 capsules taken at least 2 hours after antibiotic) led to a greater improvement in acne than either treatment alone

• This included a significant reduction in total, inflamed, and non-inflamed lesion counts

• Interestingly, the probiotic-only group also showed noted improvement across these parameters, although not as dramatic as the combination group

• Quality of life measurements showed benefit across all 3 groups, with particular benefits noted in the probiotic-minocycline combo group…

Both images from: Jung, GW. et al. Prospective, Randomized, Open-Label Trial Comparing the Safety, Efficacy, and Tolerability of an Acne Treatment Regimen with and without a Probiotic Supplement and Minocycline in Subjects with Mild to Moderate Acne. Journal of Cutaneous Medicine and Surgery, 2013,17(2),114-122


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Many more questions to be researched and answered…• Which will ultimately benefit the skin to a greater degree: oral ingestion or

topical application? Or... • Will a combination of both oral and topical prove to be the most effective?... • Might live probiotic strains offer an advantage to using probiotic derivatives,

metabolites, or supernatants?... • What about dosing? What minimal oral dose, or topical concentration, will be

necessary to see a benefit?...• Can we achieve a synergistic effect by mixing probiotics?...Or is it best to use of

one particular strain? (And for the seasoned ND’s in the crowd, do these series of rapid-fire questions harken you back to watching the end-sequence of episodes of SOAP?)


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Oral Use Topical/Cosmeceutical UseLactobacillus bulgaricus Lactobacillus plantarum (5%)

L. acidophilus Lactobacillus casei

L. reuteri Lactobacillus acidophilus

L. paracasei NCC2461 (to improve skin barrier and reduce TEWL) Streptococcus thermophilus

Streptococcus thermophilus Enterococcus fecalis

Bifidobacterium bifidum Vitreoscilla filiformis/’APF’ Aqua Posae Filiformis (patented version, marketed for seborrheic dermatitis and atopic eczema)

Commercial product containing the trio of: • Lactobacillus acidophilus (NAS super-strain, 5 Billion CFU/capsule) • Lactobacillus delbrueckii subspecies bulgaricus (LB-51 super-strain, 5 Billion

CFU/capsule) • Bifidobacterium bifidum (Malyoth superstrain, 20 Billion CFU/capsule)

Prebiotic oat extract (to promote viability of skin microbiome)

Nitrosomonas eutropha (marketed as soil-derived probiotic, to improve skin complexion and reduce sebum levels)

Bifidobacterium species (marketed for reducing skin sensitivity)

Lactococcus ferment lysate • A non-live culture containing molecules released by bacteria, in addition

to cytoplasmic and cell wall fragments • Marketed for skin renewal/exfoliation, wrinkle reduction and barrier

support

Probiotics cited in acne research (or other dermatological concern, as listed)


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PUTTING IT ALL TOGETHER

Approaches you can take…• Build upon your current and favorite

approaches…I’m looking at you, ceramide products!

• Flowchart for oily skin…can be adapted according to degree of sebum production (ex. via Skin Oiliness Scale assessments discussed)

• Create your cosmeceutical products list • Create a cosmeceutical ‘cheat sheet’ of

products containing ingredients we reviewed• Consider implementing Baumann Skin Type

Questionnaire and subsequent skin type-based product recommendations to speed product familiarity

Draelos Z.D. (2016). Oily Skin. In Draelos Z.D. et al (Eds.), Cosmeceuticals, 3rd ed. Elsevier (p. 173-174)

Baumann, L. (2010) The Skin Type Solution. New York: Bantam


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A QUICK REVIEW• Novel/Emerging oral supplements• B3: Niacin & Niacinamide• Vitex• Green tea• Zinc• Probiotics (see below)

• Skin microbiome• Support via: anti-microbial, barrier support, immunomodulatory, anti-

inflammatory, sebum reducing effects• Adjunctive effects with conventional Tx• Benefits of probiotics, both orally and topically

• Integrating it all…remember the cheat sheet!


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THANK YOU!!!

Like the nature pictures?...check out www.Pixabay.comCopyright Rob Aroup

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Documents

NATUROPATHIC AESTHETICS: ACNE VULGARIS · • Key cosmeceutical product categories • Role of the skin barrier and in -depth look at topical ceramides • Quick Look: Skin surface