Cosmeceuticals: A Review of the Scientific Evidence - Molly Wanner, MD/MBA
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Cosmeceuticals:
A Review of the Scientific Evidence
Molly Wanner, MD/MBA
Disclosures
I have the following relevant financial
relationship with a commercial interest to
disclose:
Scientific Advisory Board, Nu Skin
Grand funding, Solta
Investment, Clarity Cosmetics
What Is a Cosmeceutical?
Drugs: Mitigate, prevent, or treat disease. Affect body structure.
Cosmetic: A product intended to improve appearance
with NO effect on structure and function of skin
“Cosmeceuticals” = Cosmetic
6 out of 10 people believe that over the counter products are regulated Federal Food, Drug and Cosmetic Act (1938) • Ingredients in cosmetics and personal care products are NOT obliged to FDA standard regulatory practices (with exception of food color additives) • FDA prohibits adulterated or misbranded products
Cosmetics Are Not Regulated
What does this mean?
• FDA cannot require companies to submit
pre-marketing safety data
• FDA cannot require companies to report any side
effects of products reported by consumers
• Instead, monitoring is performed by the Personal
Care Products Counsel
-Sponsored by cosmetics industry
Savvy Consumers
Started Asking Questions
Are my products safe?
Do my products work?
Modmarcc.com
Are My Products Safe? The Clean Cosmetics movement The search for “non toxic” products
“Clean” Cosmetics:
The “Bad” List
Methylisothiazolinone (MI), methylchloroisothiazolinone (MCI), Vitamin A
derivatives, fragrance mix, phenoxyethanol, petroleum distillates,
formaldehydes, triclosan and triclocarban, toluene, resorcinol, petroleum
distillates, butylated hydroxyanisole (BHA), boric acid and sodium borate,
phthalates, placenta extract, parabens, phenoxyethanol, PEGs and ceteareth
(1,4-dioxane), formaldehydes, coal tar ingredients (including aminophenol,
diaminobenzene and phenylenediamine), petroleum distillates, placenta extractWhat Is Toxic?
• Toxicity depends on dosage (concentration
and absorption)
• There is too much of a good thing.
– Fat soluble vitamins A, D, E, K are stored
– Chronic excessive supplementation can lead to
coma or death
• “Natural” ≠ non toxic
– Poison Ivy is “natural”“Clean” Cosmetics:
Let’s See the Science
Commonly avoided chemicals grouped
into three categories:
irritants/allergens, potential endocrine
disruptors, potential carcinogens
PubMed Search performed for
chemicals in each above category, with
attention to:
• Type of study/study subjects
(human data available?)
• Dose (relevant to routine
exposure?)
• Route of administration (topical?)
Arrived at a “shortlist” of chemicals
that may be worth avoiding
Dr. Neera NathanClean Cosmetics
3 Categories of “Bad” Ingredients
Allergens
Irritants
Endocrine
Carcinogens DisruptorsAllergens and Irritants
Commonly avoided in “Clean” products
• Formaldehyde
• Fragrance
• Methylisothiazone (MI) Allergens
Irritants
• Methylchloroisothiazoli
none (MCI)
• Phenoxyethanol
• Petroleum distillates
• Vitamin AAllergens and Irritants
What does the science back up avoiding?
• Formaldehyde – hair straightener
• Fragrance
• Methylisothiazone (MI) - preservative
• Methylchloroisothiazolinone (MCI) - preservative
• Phenoxyethanol Allergens
Irritants
• Petroleum distillates
• Vitamin A
Allergens of the yearAllergens and Irritants
What can stay in the cosmetic bag?
• Formaldehyde
• Fragrance
• Methylisothiazone (MI) Allergens
Irritants
• Methylchloroisothiazoli
none (MCI)
• Phenoxyethanol
• Petroleum distillates
• Vitamin AEndocrine Disruptors
Imitate hormones & interfere with normal signaling of chemical messengers
Endocrine
DisruptorsDES (Diethylstilbestrol)
Endocrine disruptor in Medical History
• Synthetic estrogen given orally to women
in 1940s to 1970s to prevent miscarriage
• Linked to clear cell adenocarcinoma of the
vagina and cervix in daughters of women
who received this medicationEndocrine Disruptors
What does the science back up avoiding?
Commonly avoided in “Clean” products
• Triclosan and triclocarbon
• Parabens
• Phthalates
• Toluene
• Resorcinol
• Petroleum
• Butylated hydroxyanisole
• Boric acid and sodium borate
? Endocrine
• Placenta extract Disruptors
• Phenoxyethanol
More research is needed.More Research Is Needed
Toxicity depends on concentration and absorption
• Most studies performed in vitro and in
animals
• In animal studies, ingredients studied at high
doses, orally or subcutaneously
• In human studies, source is unclear, not
specifically topical, conflicting studiesEndocrine Disruptors
• Parabens – • Universal
preservative, • Many sources
antimicrobial • Absorbed through skin
• Phthalates – softener in • Animal studies
shampoos and nail
polish • Difficult to link to
topicals
• Triclosan and
triclocarbon – • No definitive link to
antimicrobial in human disease
toothpaste and
deodorantParabens
Preservative in cosmetics, moisturizers, shampoos,
food additives, food packaging, pharmaceuticals
• Penetrate skin. 99%
rapidly metabolized in
skin to weaker
metabolite.
• Weak estrogen
– 4 most common
parabens 10,000 less
potent than estradiol
Fransway AF et al. Paraben Toxicology. Dermatitis 2019; 30: 32-45.
Fransway AF et al. Parabens: Contact (Non)allergen of the year. Dermatitis 2018.
Final amended report of safety assessment of methylparaben, ethylparaben, propylparaden, isopropylparaben, and benzylparaben as used in cosmetic products. Inter
J Toxicology 2008; 27: 1-82.
Darbre et al. J applied toxicology 2014; 34: 925-938.
Harley et al. Human reproduction 2019; 34: 109-117.In Vivo Studies of Parabens Conflict
Are parabens endocrine disruptors?
YES NO
• 338 children in farmworking • 1239 girls in NYC, Cincinnati,
community San Francisco: No impact on
• Increased urinary levels of puberty
methylparaben associated • Human studies: no impact
with shift (1.3-1.5 months) on semen quality or sperm
in pubarche (pubic hair DNA
appearance) andPhthalate “Tha-leit”
Enhance flexibility of plastic (“plasticizers”), food wrappers, flooring,
medical devices, toys, lacquers, varnish, personal care products
• Phthalates can be absorbed
through the skin DEP
– Baby lotion in infants 8
months
• Not all phthalates are alike DEHP
Weak hormone activity
– In personal care products,
diethyl phthalate (DEP)
most common in US
Long side chain
– DEP does not have
hormonal activity
– Long side chain
phthalates have weak
hormone activity at high
doses Witorsch RJ and Thomas JA. Personal care products and endocrine disruption. Crit Rev Toxic 2010; 40: 1-30.
Janjua NR. Urinary excretion of phthalates and paraben after repeated whole-body topical application in humans. Int J andrology 2008; 31: 118-130.
Sathyanarayana S et al. Baby Care Products. Pediatrics 2008; 121: 260-8.
Sathyanarayana S et al. Baby Care Products: Possible sources of infant phthalate exposure. Pediatrics 2008; 121: 260-268.Phthalate
Endocrine disruption potential?
YES NO
• Inverse association of • No association in pubertal
concentration with breast timing in girls or boys
development (Wolff) (Harley)
• Possible association of
DEHP on male genitalia
(Swan) Long side chain
Weak hormone activity
High doses impact rat fertility
Witorsch RJ and Thomas JA. Personal care products and endocrine disruption. Crit Rev Toxic 2010; 40: 1-30.
Wolff MS. Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates and phenols and pubertal stages in girls.
Environ Health Perspect 2010; 118: 1939-1046.
Harley et al. Association of phthalates, parabens, and phenols found in personal care products with pubertal timing in girls and boys.
Human Reproduction 2019; 34: 109-117.
Swan SH. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints. Environ Red 2008; 108: 177-184.Triclosan
Antibacterial and antifungal deodorants,
toothpaste, clothing, household items
YES Avoid? NO
• Animal studies show dose • RCT of 132 subjects and
dependent impact on 0.3% triclosan in toothpaste
thyroid – no impact on thyroid
– Rat study: Dose dependent
decrease of T4 with oral
triclosan • Human studies conflict
Zorrilla LM et al. The effects of triclosan on puberty and thyroid hormones in males wistar rats. Tox Sciences 2009: 107: 56-64.
Cullinan MP et al. Long term use of triclosan toothpaste and thyroid function Science of the Total Environment 2012; 416: 75-79.
Mihaich E et al. Hypothesis-driven weight of evidence analysis of endocrine disruption potential: a case study with triclosan. Critical reviews in toxicology 2017 47: 263-285
Deierlein AL et al Phenol concentrations during childhood and subsequent measures of adiposity among young girls. Am J Epid 2017; 186: 581-592.
Li S et al. Urinary triclosan concentrations are inversely associated with body mass index and waist circumference in US general population: experience in NHANES 2003-2010. Int J Hyg Environ Health 2015; 218: 401-406.Potential Carcinogens
Commonly avoided in “Clean” products
• Formaldehyde
• Coal tar ingredients
• Petroleum
• 1-4 dioxane
• Placenta extract
CarcinogensPotential Carcinogens
What does the science back up avoiding?
Formaldehyde
• Linked to cancer in
animals and humans in Formaldehyde Placenta
high doses including extract
topical occupational
Coal Tar Petroleum
exposure distillates
• Labeled a known 1,4 dioxane
carcinogen by NIH
National Toxicology
Program
25,619 workers in the formaldehyde industry: link between formaldehyde and nasopharyngeal cancer
Beane Freeman LE. Mortality from solid tumors amount workers in formaldehyde industries.: An update of the NCI cohort.
Am J Indus Med 2013; 56: 1015-1026.Potential Carcinogens
What can we leave in the bag?
Formaldehyde Placenta
extract
Coal Tar Petroleum
distillates
1,4 dioxanePotential Carcinogens
What can we leave in the bag?
– Industrial use linked to
cancer~“chimney sweeps”
– Cohort study of 13,200
patients did not increase
risk of malignancies
Coal TarPotential Carcinogens
What can we leave in the bag?
Formaldehyde Placenta
extract
Coal Tar Petroleum
Distillates?
1,4 dioxanePotential Carcinogens
What can we leave in the bag?
• CRUDE petroleum on the
skin of 50 mice increased
skin cancer
• Cosmetics have highly
refined petroleum Petroleum
distillates Distillates
– Poly aromatic Mineral oil Petrolatum liquid
hydrocarbons are not Light mineral oil
Heavy mineral oil
Petroleum oil
Paraffinum liquidum
present (known Liquid Paraffin
carcinogen) Mineral oil mist
Paraffin oil
• 4 Human studies:
petrolatum stays in
superficial skin due to size
Clark CR, Walter MK, Ferguson PW, Katchen M. Comparative dermal carcinogenesis of shale and petroleum-derived distillates.
Toxicol Ind Health 1988; 4: 11-22.
Rawlings AV and Lombard KJ. A review on the extensive skin benefits of mineral oil. In J Cos Sci 2012; 34: 511-518.
Petry T et al. Review of data on the dermal penetration of mineral oils and waxes used in cosmetic applications. Tox Letters 2017;
280: 70-78.Potential Carcinogens
What can we leave in the bag?
More data
Formaldehyde Placenta
extract
Coal Tar Refined
Petroleum
1,4 dioxane
More dataDo My Products Work?
Are my products safe?
Do my products work?
Modmarcc.comCommon Cosmeceuticals • Vitamins A, B, C • Growth Factors • Peptides • Sugars
Koo E, Kimball A, and Wanner M. Cosmeceuticals. In: Griffiths C, Barker J, Bleiker T, Chalmers R, and Creamer D Eds. Rook’s Textbook of Dermatology, 9th Edition. Wiley-Blackwell, 2016.
Do My Products Work?
Biologic Clinical
Absorbed? Yes
effect? effect?Biologic Clinical
Absorbed? Recommend
effect? effect?Absorbed?
Concentration and Molecular
Weight Influences Absorption
Absorption (J) = Permeability coefficient * Concentration
(Partition coefficient*Diffusion coefficient/Length of path of diffusion)Can Vitamin A be absorbed through the skin? DOES MY PRODUCT WORK?
Vitamin A: Tretinoin Is Our Gold
Standard for Photoaging
• 6 double blind, controlled studies
• 2 largest trials
– 619 subjects
– Followed for 6 months
– 86% had global improvement
vs 44% control
Weinstein GD et al. Arch Derm 1991
Olsen EA. JAAD 1992. Wanner et al. JDD 2015; 14: 13-18.OTC Vitamin A: Retinaldehyde Induces Retinoic Acid Activity in Humans More Than Retinol Retinol Retinaldehyde (Retinal) All transretinoic acid (Tretinoin) Duell EA et al. Extraction of human epidermis treated with retinol yields retro-retinoids in addition to free retinol and retinyl esters. JID 1996; 107: 178-182. Saurat JH et al. Topical retinaldehyde on human skin: biologic effects and tolerance. JID 1994; 103: 770-774.
Vitamin A – Retinaldehyde
Reduces Fine Lines
• 125 subjects,
retinaldehyde 0.05 vs Tretinoin RA Placebo
tretinoin 0.05 vs
placebo
• Silicone replicas of
crows feet
• Improvement of
photoaging
Creidi P et al. Profilometric evaluation of photodamage after topical retinaldehyde and retinoic acid treatment. JAAD 1998; 39: 960-5.Retinol Reduces Fine Lines • Retinol 0.4% (36 subjects): -1.64 point improvement wrinkles vs control on 9 pt scale (statistically significant) • Concentration in cosmeceuticals can be as low as 0.08% Lee et al. A newly synthesized photostable retinol derivative (retinyl N-formyl aspartamate) for photodamaged skin: profilometric evaluation of 24-week study. J. Am. Acad. Dermatol. 2006;55:220–4. Manela-Azulay M, Bagatin E. Cosmeceutical vitamins. Clin Dermatol 2009; 27: 469-74. Kafi et al. Improvement of naturally aged skin with Vitamin A (retinol). Arch Derm 2007; 143: 606-612.
My Approach to Vitamin A • Retinaldehyde when can not tolerate tretinoin • Concentration matters
Does My Product Work?
Vitamin B3
Nicotinic acid
Vitamin B3
Niacin
Nicotinamide
/ Inositol
Niacinamide hexanicotinateVitamin B3 • Precursors of NAD(H) and NADP(H) enzymes – oxidative metabolism • +ceramides and keratinocyte differentiation
Can Vitamin B3 Be Absorbed
Through the Skin?Vitamin B3 Improves
Skin Barrier Function
Placebo
5% myristyl nicotinate
(nicotinic acid derivative)
Increases skin thickness
Promotes epidermal differentiation
Decreases TEWL
Jacobson EL et al. A topical lipophilic niacin derivative increases NAD, epidermal differentiation and barrier function
In photodamaged skin. Exp Dermatol 2007; 16: 490-499.
Bermudez Y et al. Nicotinic acid receptor abnormalities in human skin cancer. Plos One 2011; 6: 1-10.Vitamin B3: 4-5% Niacinamide Improves Acne,
Photoaging and Melasma
Acne Photoaging
50 subjects
80 subjects 5% reduction in wrinkles vs control
Improved, not as much as 1% clindamycin
Melasma
27 subjects
44% improved on niacinamide vs 55% hydroquinoneBefore After
Reduced brown spotsMy Approach to Vitamin B3
Moisturizer or spray for Acne Sensitive skin and photoaging
4% concentration, pH 4-7Antioxidant Vitamin C Collagen
Can Vitamin C be absorbed through the skin? DOES MY PRODUCT WORK?
Vitamin C Absorption Maximized at
Concentration of 20% and pH Less Than 3.5
Pinnell et al. Topical L-ascorbic acid: Percutaneous absorption studies. Dermatol Surg 2001;
27:137-42.Ferulic Acid Stabilizes Vitamin C – After 2 months, 0% of L-ascorbic acid remained – >90% L-ascorbic acid present at 2 months when formulated with Ferulic acid Pinnell et al. Dermatol Surg 2001; 27:137-42 Lin et al. JID 2005; 125:xi-xiii. Austria R et al. J Pharm Biomed Anal 1997: 795-801.
Concentration Matters for
Collagen Stimulation
Increase collagen
15% Vit C increased collagen I and III in skin biopsies
by 20%-25% (pVitamin C Is Photoprotective
Increases sun protection
15% Vit C 10% Vit C
Valacchi et al. Protective effects of topical vitamin C compound mixtures
Against ozone-induced damage in human skin. JID 2017; 137: 1373-1375.
Lin et al. JID 2005; 125:xi-xiii.Clinical Studies:
Vitamin C and Photoaging
• 3 studies, 10-20 subjects, 1 RCT
• Improvement statistically significant, but
variable
Fitzpatrick et al. Dermatol Surg 2002; 28: 231-236.
Traikovich SS. Arch Otolaryngol Head Neck Surg 1999; 125; 1091-8.
Humbert 2003. Exp Dermatol 2003; 12: 237-244.My Approach to Vitamin C • Photoprotective effects>morning • Dark bottle, small opening • Ideal pH 3.5 (sting) > not for sensitive skin • Concentration in 10-15% range • Formulation with ferulic acid may be helpful
Should I Use This Product?
What does the science support?
NO YES
• Formaldehyde • Retinol or
• Fragrance Retinaldehyde
• Methylisothiazone (MI) • Niacinamide or nicotinic
• Methylchloroisothiazoli acid
none (MCI) • Ascorbic acidYou can also read
