Home :: Retinol
OVERVIEW
History and Significance
Applications

CHEMISTRY
General Manufacturing Process
Available Formulations
Biologic Activity
Rejuvenation
Dermal Hydration
Comedolysis

APPROVED INDICATIONS AND THERAPEUTIC USE
Acne
Clogged Pores
Rejuvenation
Hyperpigmentation
Solar Keratosis

CLINICAL CONSIDERATIONS
Patient Instructions
Duration and Frequency of Treatment
Contraindications, Warnings, Precautions

PRODUCT SELECTION FOR RESULTS

REFERENCES

Retinol  

 OVERVIEW

Retinol is one of the most usable forms of Vitamin A, a fat-soluble vitamin and diterpenoid. Retinoids include the compounds retinoic acid, retinal (aldehyde) and retinyl ester. These compounds are available from plant and animal sources. Vitamin A is essential for proper epithelial function,1 and available retinoic acid is procured by hyaluronic acid in the keratogenous zone to increase dermal moisture.

 History and Significance

Vitamin A was identified as a fat-soluble nutrient in 1913, and synthesized in 1947. However, vitamin A deficiency has been reported throughout history, including night blindness and pale dry skin (xerosis). The FDA established dietary guidelines for Vitamin A and in 1971 approved prescription topical medications containing derivatives of Vitamin A for treatment of skin disorders such as acne. Studies have shown that retinol, like hyaluronic acid, is essential for cell proliferation but decreases with age, as measured in the stratum corneum, epidermis, and dermis.3 Topical formulations provide therapeutic benefits for keratolysis and moisturization with minimal systemic absorption.4

 Applications

Topical retinoids include tretinoin and adaptalene. Tretinoin is widely used for acne treatment for its strength, sebum reduction, and keratolytic effect. Retinoids increase sensitivity to sunlight5 and are used as monotherapy and in combination treatments for facial rejuvenation, hyperpigmentation, and solar keratoses.6

 CHEMISTRY

Retinol is the alcohol form of vitamin A that is a yellowish liquid of varying viscosities and insoluble in water.

Synonyms: 5-apo-B-caroten-15-ol (3,7-dimethyl-9-(2,6, 6-trimethylcyclohex-1-enyl) nona-2; anti-infective vitamin; anti-xerophthalmic vitamin; axerophtholum; biosterol; oleovitamin A; retinal (vitamin A aldehyde); vitamin A1

Molecular formula: C20H30O



 General Manufacturing Process

Retinol is produced from the hydrolysis or reduction of retinyl esters and retinal for metabolism. It is commercially produced, similarly, with retinal synthesis through an acid or base reduction of a pentadiene derivative followed by acidification/hydrolysis of the isomeric mixture to produce retinol. Retinol is an alcohol that is stabilized as retinyl acetate or palmirate (dietary supplement).

 Available Formulations

Retinol is combined with other agents for dermatologic use to optimize acne treatment and to support tissue repair and hydration. KAVI products contain enhanced retinol, which maintains its potency longer than most retinol products.

 Biologic Activity

Topical application of retinoids has been shown to modify the architecture of the epidermis, dermis, and sebaceous glands with minimal systemic absorption. Retinol and synthetic retinoids induce hyperproliferation through transcriptional regulators for a dose-dependent expansion in the numbers of cell layers of the stratum spinoseum and stratum granulosum with minimal changes in the number of layers in the stratum corneosum.8 Vitamin A is directly involved in controlling the biosynthesis of specific glycoproteins in all epithelial tissues. A proposed concept is that an increased concentration of the retinoid in the target tissue enhances the potential of the tissue to maintain the normal phenotype.9 A second pathway for retinol is currently being studied to identify retinol metabolites, which function as intracellular mediators of cell physiology (different from the retinoic acid pathway which does not support B cell growth).10 Topical retinol provides rejuvenation benefits through restoration of normal epithelial function, multilayer support to dermal proliferation, and dermal matrix maintenance. Retinol also provides comedolytic benefits through mediation of sebum activity and reinforced keratinization.

 Rejuvenation

The retinoic acid pathway interacts with transcriptional regulators to induce hyperproliferation in the stratum spinseum and stratum granulosum. Without supplemental forms of retinoic acid to help reduce metalloproteinase induction,12 elevated levels of metalloproteinases in damaged dermal layers (as evidenced in photodamaged skin) induce degradation of collagen and elastin.

 Dermal Hydration

While retinol is insoluble in water, its bioavailability in the dermal layers is hydrolyzed to retinoic acid, which is subsequently sequestered by hyaluronic acid in the extracellular matrix to increase water content in cells. These mechanisms effect normal, hydrated dermal development.

 Comedolysis

The comedolytic effect of retinoids is multifaceted: retinol penetrates sebaceous glands; transcriptional receptors promote reduction of sebum secretion; anti-inflammatory effects of retinoids reduce Propionibacterium acne proliferation; and mild keratolysis is induced as the retinoids promote normal epithelial function and repair:

1. Penetration
Vitamin A is fat-soluble; retinol is insoluble in water and miscible in organic compounds. Retinol penetrates the sebaceous glands to the dermal layers.

2. Sebum Reduction
In murine models, retinoids have a dose-dependent hyperplastic response in reducing sebum secretion from the sebaceous glands.8

3. Anti-Inflammatory Effect
Hydrolysis of retinol to retinoic acid produces a mild anti-inflammatory effect which inhibits proliferation of P. acne in sebaceous glands.11 13-cis-retinoic acid functions as an immunopotentiator thereby stimulating antibody production against antigens in acne patients.

4. Keratolysis and Epidermal Repair
Retinol and synthetic retinoids have a dose-dependent effect in increasing the number of layers of the stratum spinoseum and stratum granulosum without significant changes in the number of layers in the stratum corneosum. This proliferation of cells and number of layers induce a mild keratolytic effect for normal tissue function.

 APPROVED INDICATIONS AND THERAPEUTIC USE

APPROVED INDICATIONS
Acne
Clogged Pores
Rejuvenation
Premature Aging,
Collagen Breakdown, and
Fine Lines

Dermal Hydration
Hyperpigmentation
Photoaging
Age Spots and Freckles
Melasma
Solar Keratosis

The effects of retinol and the benefit of vitamin A can be included in treatment strategies and regimens with minimal systemic absorption. Continued use in lower doses with UVA/UVB protection provides sustained effects.

 Acne

Propionibacterium acnes is a normal inhabitant of sebaceous follicles. Abnormal proliferation of P. acnes alters the skin's pH, producing acne and acne infection. Topical retinoids are hydrolyzed to retinoic acid, which supports normal tissue function and repair, and provides a mild anti-inflammatory effect to reduce P. acnes. Retinol is insoluble in water, which facilitates its penetration into sebaceous glands. Retinoids have been studied to have a dose-dependent effect to modulate sebum secretion.

 Clogged Pores

Retinoids have a comedolytic effect in maintaining the stratum granulosum to achieve normal tissue function: initially mild comedolysis and keratolysis opens clogged pores. Retinol penetrates sebaceous glands, modulating sebum secretion and producing mild anti-inflammatory and immunostimulatory effects to control infection and P. acne proliferation. Continued use promotes tissue repair and normalization.

 Rejuvenation

Retinoic acid plays an essential role in cell proliferation and collagen synthesis. Decreased levels of retinoic acid have been attributed to tissue degradation and vitamin deficiency. Vitamin A supplementation through topical application of retinoids has been shown to produce rejuvenation effects.

 Premature Aging, Collagen Breakdown, and Fine Lines

Elevated levels of metalloproteinases have been measured in damaged tissue. Over time, continued epithelial damage can result in dehydration and wrinkles. Retinoic acid reduces metalloproteinase induction, promoting collagen scaffold retention and tissue hydration.

 Dermal Hydration

Tissue damage and dehydration can produce lines and wrinkles. Biologic compounds such as hyaluronic acid engage retinoic acid to increase water in cells, thereby creating a hydrated scaffold for collagen synthesis. Retinoic acid plays a role in maintaining the integrity of cellular membranes, as evidenced by its function to establish normal tissue function through cell proliferation.

 Hyperpigmentation

Retinoids play an important role in dermal repair and support cell proliferation. With minimal absorption to the body, retinoids are considered a non-surgical option to treat some forms of hyperpigmentation.

 Photoaging (Sun Spots)

As with facial rejuvenation, retinoids have been shown to be effective in counteracting the effects of prolonged tissue damage by reducing metalloproteinase induction and promoting the structural formation of collagen and the dermal matrix.14

 Age Spots and Freckles

Retinoic acid blocks metalloproteinase induction that is stimulated by UVB exposure. The effects of mild keratolysis and tissue repair can reduce the abnormal stratum granulosum that has been associated with age spots and freckles.15,16 The retinoic acid pathway further serves to interrupt melanin synthesis.

 Melasma

Melasma is facial hyperpigmentation that is often manifested among pregnant women due to wide shifts in hormonal balance. The biologic pathway of retinoic acid serves to interrupt melanin synthesis and to reduce redness and irritation associated with cellular damage and degeneration. Retinoids are a treatment consideration to reduce melasma and support dermal regeneration.15,16 Topical retinoids have been shown to have minimal absorption though caution is advised for use in pregnant women and children.

 Solar Keratosis

Solar keratoses are common premalignant skin legions that may advance to squamous cell carcinoma. It is hypothesized that tissue damage due to sun exposure initiates the abnormal formation of lesions; decreased production of biofactors associated with age is also a factor in susceptibility of progression. Clinical studies have shown the effectiveness of oral and topical retinoids in reducing the severity and proliferation of dry, itchy lesions.8,16

 CLINICAL CONSIDERATIONS

Enhanced Retinol is included in the KAVI Anti-Aging Systems to reduce fine lines, variable pigmentation (such as age spots), and uneven texture. Enhanced Retinol is included in the KAVI Anti-Acne Systems to reduce the probability of new comedone formation and future acne infection while treating existing clogged pores and acne.

 Patient Instructions; Duration and Frequency of Treatment

Apply a thin layer of Enhanced Retinol 0.30% directly on the skin once or twice daily after cleansing to stimulate collagen production and open pores.
If skin becomes dry or inflamed, discontinue use for one week and recommence application at a reduced frequency (e.g., if former regimen involved twice-daily application, recommence with once-daily application).

 Contraindications, Warnings, Precautions

For external use only. Use as directed by your healthcare professional. Use with caution under the supervision of a healthcare professional in children and pregnant women. Avoid application to irritated or open wounds. Use sunblock on areas exposed to the sun. Discontinue use for one week if excessive drying or peeling is observed.

 PRODUCT SELECTION FOR RESULTS

Retinol is a safe and effective option to enhance to any dermatologic treatment plan. Enhanced Retinol 0.30% includes the benefits of retinol with the stability of a longer shelf life to promote continued results during treatment and maintenance cycles. KAVI Enhanced Retinol 0.30% is formulated to complement all KAVI treatment systems.

Additional information on Enhanced Retinol 0.30%
Additional information on the KAVI Anti-Aging System II for Normal or Dry Skin
Additional information on the KAVI Anti-Aging System II for Oily or Combination Skin
Additional information on the KAVI Anti-Acne System II for Normal or Dry Skin
Additional information on the KAVI Anti-Acne System II for Oily or Combination Skin

 REFERENCES

1. "Vitamin A (Retinol)", National Institutes of Health. Medline Plus. March 1, 2008. Available online. Accessed June 5, 2009.
2. "Retinol", National Cancer Institute. NCI. Available online. Accessed June 5, 2009.
3. Yan J, Xia Q, Webb P, et al. "Levels of Retinyl Palmitate and Retinol in Stratum Corneum, Epidermis and Dermis of SKH-1 Mice", Toxicol Ind Health. Apr, 2006; 22(3):103-12.
4. Kasilo OJ, Nhachi CFB. Retinol. "Inter-Organization Programme for the Sound Management of Chemicals", INCHEM. December 1989. Available online. Accessed June 5, 2009.
5. "Wrinkle creams: Your Guide to Younger Looking Skin", Mayo Clinic. October 11, 2008. Available online.
6. OTC Ingredient List. FDA. 2008. Available online. Accessed June 2, 2009.
7. Radspeiler, A, Ruettimann A. Manufacture of Retinoids. World Intellectual Property Organization. August 4, 2003. Available online. Accessed June 5, 2009.
8. Lowe NJ, Marks R. "Retinoids: A Clinician's Guide", London: Informa Health Care; 1998; pp.1-7.
9. De Luca LM, Sasak W, Adamo S, et al. "Retinoid Metabolism and Mode of Action", Environ Health Perspect. 1980; 35:147-152.
10. Buck J, Myc A, Garbe A, et al. "Differences in the Action and Metabolism Between Retinol and Retinoic Acid in B Lymphocytes", J Cell Biol. 1991; 115(3):851-859.
11. Bikowski JB. "Mechanisms of the Comedolytic and Anti-Inflammatory Properties of Topical Retinoids", J Drugs Dermatol. Jan-Feb, 2005.
12. Fisher GJ, Datta SC, Talwar HHS, et al. "Molecular Basis of Sun-Induced Premature Skin Aging and Retinoid Antagonism", Nature. 1996; 379:335-339.
13. Jurzak M, Latocha M, Gojniczek K, et al. "Influence of Retinoids on Skin Fibroblasts Metabolism in Vitro", Acta Pol Pharm. Jan-Feb, 2008; 65(1):85-91.
14. Samuel M, Brooke RC, Hollis S, et al. "Interventions for Photodamaged Skin", Cochrane Database Syst Rev. 2005; (1):CD001782. Review.
15. Bertin C, Zunino H, Lanctin M, et al. "Combined Retinol-Lactose-Glycolic Acid Effects on Photoaged Skin: a Double-Blind Placebo-Controlled Study", N. Int J Cosmet Sci. 2008; 30(3):175-82.

 
 
 
 
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