NATURAL THERAPEUTICS: ANTI-PHOTOAGING
Stephen Holt MD, Distinguished Professor of Medicine (Emerite), Scientific Advisor, Natural Clinician LLC, Little Falls, NJ
Ultraviolet radiation (UVR) in sunlight is the most important cause of skin damage and aging 1-5. This form of radiation causes skin aging by several mechanisms including free radical generation, DNA damage, collagen breakdown, the induction of immune defects and cell death 1-5. In addition, repeated damage to the skin by sun burn is a primarily risk factor for the development of cutaneous neoplasia, including melanoma.
While photoaging may be considered to be the pivotal cause of skin aging or damage, other factors operate 1, 6. Cigarette smoking, various environmental pollutants and synthetic chemicals, (including those present in cosmetic products or sunscreens), can all contribute to dermal pathology and perhaps skin aging 1. These external factors may often combine with “intrinsic propensities” to aging. Intrinsic skin aging is characterized by thinning of dermal and epidermal layers of the skin coincidental with the evolution of “immune senescence” 1, 6. The recognition that photoaging is caused primarily by UVR has led to conventional wisdom that excessive exposure to sunshine should be avoided. The risks of cutaneous sun damage have led to the widespread application of techniques to protect the skin from sun light, most often using sunscreening techniques.
The objectives of this article are to examine factors that propagate skin phototoxicity (photoaging) and examine natural ways to combat this major public health concern.
Ultaviolet radiation (UVR) causes variegate cutaneous damage to the skin. This UVR is classified by wavelength into UVA (320-400nm) UVB (290-320 nm) and UVC (100-290 nm). It is the atmospheric UVB type of radiation that is the main cause of cutaneous damage (sunburn), but UVA may result in deeper penetration of the dermis and cause significant dermal tissue damage 1. There is relatively little exposure to UVC because this form of UVR is absorbed efficiently by the ozone layer surrounding the earth 1. That said, some geographic locations have a reduced ozone shield e.g. Australia. Exposure to UVC can occur from artificial radiation sources such as mercury arc lamps or light sources that are used for sterilization etc. Much less is known about the cutaneous effects of UVC compared to other types of UVR. The adverse consequences of tissue exposure to UVR are summarized in Table 1.1
CUTANEOUS DAMAGE COMMENTS
FROM UVB AND UVR
Free radical generation Damage to cell membranes, mutations in DNA and activation of metalloproteinase enzymes, resulting in collagen breakdown
DNA Damage DNA forms cyclobutane dimers and adducts. Alteration of cell repair mechanisms occur with compromise of endonuclease 5 (T4N5)
Collagen Breakdown Crosslinking of collagen, alteration of remodeling ability of metalloproteinase enzymes and abnormal elastin accumulation. These factors contribute to dermal breakdown and skin wrinkling
Immune Disorders Langerhans Cell (antigen-presenting cells) function is compromised, with inflammatory cytokine formation, neuropeptide release from skin sensory nerves, inhibition of histamine release from mast cells and induction of tolerance by immune suppressor cells.
Apoptosis Dysregulation Compromise of cell replication with stability of the genome and induction of apoptosis are caused by UVR, with cell proliferation and cancer formation
Table 1. Tissue changes that are induced by UVR exposure (UVB is the principal miscreant) (Reviewed in detail 1)
Treatment of Photoaging
There are several approaches to the management of sun-damaged skin, but the outcome of many applied treatments are often time-limited in their clinical outcome (Table 2) 7, 8. Dermatological treatment of photoaging often involves attempts to correct the many skin abnormalities that are seen after long-term exposure to sun light7, 8. These adverse cutaneous reactions to UVR include: dry coarse epidermal changes (leathery skin), wrinkles, loss of skin elasticity, vascular changes (senile purpura, telangiectasia, easy brusing etc), freckling or lentigenous changes, general tissue thinning and benign or malignant neoplasia (solar keratosis, basal cell carcinoma, squamous cancer and melanoma)7, 8. Popular approaches for the induction of aesthetic improvements in the presence of intrinsic or extrinsic causes of skin aging are summarized in Table 2 7, 8.
Skin Peels Chemicals are used to remove the surface layers of the skin with variable improvement in irregular pigmentation and superficial scars. Combined often with intense moisturizing strategies.
Botulinum Toxin (Type A) This toxin paralyses muscle groups with prevention or resolution of minor or moderate skin wrinkles.
Collagen Injections (Fillers) Injections of purified (bovine) collagen or other “fillers” to correct significant wrinkles, scars, facial lines and furrows.
Dermabrasion (microdermabrasion) Removing the superficial layers of the skin with an electrical abrasion instrument. Microdermabrasion utilizes particles passed through a vacuum tube to remove skin and stimulate its growth.
Fish Nibbling Live fish are exposed to skin of an individual in a large fish tank. The fish nibble away at surface layers of the skin (used mainly in Asia).
Laser Skin Resurfacing High energy thermal ablation (monochromatic light) to remove damaged skin or the use of non-ablative resurfacing. Resurfacing techniques often combine laser light and electrical energy.
Intense Pulsed Light Therapy A non-ablative therapy using light of multiple wavelengths.
Topicals Estrogen or progesterone creams, liposome complexes, various cosmeceuticals and antioxidants, etc. A variable evidence-base for efficacy
Table 2: Popular esthetic treatments for photoaging of the skin. Specific skin
disorders related to photoaging required specialized interventions.9
The concepts of beauty or skin health from “within the body” are dawning in the practice of skin care. Protomorphogens for skin, hair and nail care, antioxidants, and even “oral sunblockers” (Polypodium spp.) are being used increasingly 10.Oral nutraceuticals complement actions of topical cosmeceuticals and vice versa 10.
Sunlight (UVR) exposure results in many biophysiological changes that result in several types of photodermatosis (Table 3). The clinician should be vigilant in recognizing causes of photosensitivity that require special intervention. Diagnostic applications of “phototesting” utilize local light applications that assist in detecting photosensitizing agents.
Photosensitive State Causation
Metabolic Increased presence of porpyrins in the skin e.g. porphyria cutana tarda.
Genetic Bloom Syndrome,Rothmund Thomson syndrome and Xeroderma Pigmentosum etc.
Skin disease (Unpredictable effects) Acne, Rosacea, Lupus, Erythematosis (discoid or systemic), Atopic dermatitis, Psoriasis. Some dermatoses may improve with modest sunlight (a contrarian phenonomenon).
Chemical / Drug Solar interactions Topical or systemic photosensitizing agents include drugs (e.g. amiodarone, tetracycline), dietary supplements (e.g. St.Johns Wort) and contact with a variety of botanicals, synthetic chemicals, fragrances, dyes and germicidal compounds.
Unknown causes of Solar Hypersensitivity Solar rashes such as urticaria, actinic prurigo, polymorphic light eruptions, chronic dermatitis and “pseudprorphyria”
Table 3: A general classification of the causes of skin photosensivity, with examples.
The presence of damaging UVR in the environment is often underestimated. Even dull weather in a tropical climate can result in UVR exposures that precipitate significant sunburn. While sunprotection with sun shades or glass enclosures is useful for partial outdoor protection, a significant amount of UVA can penetrate glass or “shutters” that are installed to “protect homes”. Sun-proof clothing (with high UPF values) have been recommended, but this approach is often seen as impractical because it involves the wearing of relatively thick clothes of dark color, together with clumsy accessories (e.g. sombreros, socks, etc.)
The most widespread direct attempts to provide sunprotection involve the use of a variety of topical agents (sunscreens) 1-11. Topical sunscreen products often contain chemical products that absorb UVR and dissipate heat within the dermis. Some topical sunscreen agents involve the application of physical barriers that reflect sunlight. These latter types of sunscreen are effective when applied in a careful manner to cover the skin entirely; and they do not carry the same risks of toxicity that are associated with the use of many synthetic chemical sunscreen (e.g. oxybenzones, benzophenones, methoxy dibenzoylmethane, PABA, etc.) 11-14
While many people espouse the benefits of the use of sunscreens, the safety and efficacy of many types of these products have been questioned in many research studies. Topical sunscreen products may cause several medical disorders (Table 4).
• Contact Allergy
• Free radical generation
• Unacceptable esthetics
• Local toxicities
• Vitamin deficiency (D)
• Systemic toxicities
Table 4: Clinical disorders associated with the use of topical sunscreens. The putative toxicity of many synthetic sunscreens is a public health concern that remains underexplored 11-14.
Characteristics and Actions of Topical Sunscreens
The objectives of using sunscreen involve not only the prevention of sunburn, but the avoidance of cumulative cutaneous damage by repeated UVR exposure. Cumulative damage to the skin caused by UVR is dependent on both the magnitude and duration of radiation exposure, but chronic skin damage can occur without obvious or premonitory signs or even a documented history of significant or recurrent sunburn. Broad spectrum sunscreens block both UVA and UVB, but there is no international standard for UVA blockage. Unfortunately, there are no sunscreen products that block all UVR effectively and studies of routine or casual users of these products show that sunscreens are often applied in a patchy manner, especially on the face. Many sunscreens are easily washed off by swimming, therefore, despite claims of efficacy of topical agents, many of these sunscreens are applied in a manner that cannot afford adequate or widespread sun protection1, 11, 12.
The concept or “strength” of sun-blocking is described by the SPF value of a topical agent. This SPF value is defined as the ratio of the energy (UVR) needed to induce a minimal skin reddening (erythema), in the presence of the production of the same skin reaction in the absence of a sunscreen 1, 13. Theoretically, the higher the SPF value the larger the amount that sun exposure can occur without sunburn or the percentage of UVB light absorption (dosing) to the skin (e.g. SPF 15 absorbs about 92% of UVB and SPF absorbs about 97.5% of UVB). The concept “theoretical” SPF or solar protection must be considered in relationship to SPF values, given the inevitable failure of sunscreens to provide complete and lasting coverage 1, 12. To be effective, the topical sunscreens must be used with careful and repeated interval application. This requires good compliance which is often absent or compromised during recreational activities. Education about behavioral changes during outdoor recreation is underutilized in society.
Despite the recognized disadvantages and limitation of topical sunscreen products, several animal and human studies have demonstrated their preventive benefits for reducing aging changes in the skin (decreased wrinkling, reduction of skin sagging and abnormal elastin deposition), decreasing direct or immune damage (reduction of pyrimidine dimer formation and protection of Langerhans cells with reduction of UV-induced cutaneous hypersensitivity. In addition, the correct use of sunscreens may cause a statistically significant reduction in the prevalence of precancerous skin lesions1, 14. While there is good reason to believe that the efficient use of sunscreen products may reduce the incidence of melanoma, this finding has not been demonstrated in a convincing or consistent manner in some controlled clinical observations. Aggregate information links the occurrence of melanoma to UVR exposure 1, 15.
Effectiveness of Topical Sunscreens
Recent toxicological studies have raised major concerns about the safety and effectiveness of many commercially available topical sunscreens 1. These studies have uncovered the current limitations of regulatory controls or approvals of chemical sunscreens, especially in the US. A landmark, recent study of the safety and effectiveness of 952 topical sunscreen products implies that about four out of five of the most popular sunscreens do not offer efficient sun protection; and many contain ingredients with putative or actual toxicity.
This recent study was performed by the Environmental Working Group (EWG) with startling outcomes (www.cosmetics-database.com). In this study, leading brands of topical sunscreens appeared to be among the least effective. For example, only one of more than one hundred products produced by Neutrogena® or Banana Boat® was recommended as safe and effective for use as a consequence of these studies; and none of the forty one products marketed by Coppertone® met standards of safety and efficacy that have been espoused by the EWG. This comprehensive study utilized ratings of products based on a compilation of information derived from technical literature and combined industry, government or academic data on sunscreens. The findings of the study are summarized in a descriptive manner in Table 5.
• Many sunscreen products carry questionable claims e.g. “all day protection”, “blocks all harmful rays” and “mild as water”
• Nanoscale components pose safety concerns, especially in powders or sprays, because of systemic access by accidental inhalation and greater systemic absorption.
• Components of sunscreens (organochemicals) may be absorbed into the body with toxic effects (much toxicity is predicted but unknown).
• Some components of sunscreens release free radicals when they interact with UVR, thereby compounding oxidative to damage the skin (an aging effect).
• Several ingredients are linked to allergic reactions, hormonal effects (xenoestrogens) and may accumulate in body tissues with secondary metabolic effects (perhaps toxic lipogenesis).
• Many sunscreens (about 48%) contain unstable ingredients that decompose in a variable time period (minutes to hours)
• Regulatory controls that govern sunscreen compositions are inadequate e.g. failure to approve safe sunscreen ingredients, lack of sanction against inflated claims, no requirements for detailed stability data and a lack of focus on approving agents that block both UVA and UVB forms of radiation. Overall, there is a lack of mandatory sunscreen standards
Table 5: Descriptive comments on the outcome of the EWG study on the safety and
efficacy of leading brands of topical sunscreen products. (www.cosmetics-database.com)
There are many published reviews of sunscreen products in books, magazines and on the internet (e.g. www.consumersearch.com) However, the basis for the ratings of certain products is often not clear in consumer reports and it is perhaps biased by economic influences, most notably advertising revenue obtained by the publications from certain purveyors of cosmetic components. This type of bias plagues the dietary supplement, pharmaceutical and cosmetics industries, in a chronic manner. Some claims, by editorial staff, that reports are “objective” have not been supported by disclosure of the basis of rating systems that are used to make conclusions about the efficacy and safety of cosmetic (or nutraceutical) products.
Toxic Consequences of Topical Sunscreens
Mineral-based sunscreens containing zinc oxide (and perhaps calcium compounds or titanium dioxide) are quite effective and safe because they are not absorbed to a significant degree by normal skin. Certainly, zinc oxide is to be preferred because it has intrinsic healing properties and other potential benefits. At present, there are many synthetic chemicals that are approved by the FDA for use as active ingredients in sunscreens. However, some brands of sunscreen sold in the US contain chemicals that have not yet been approved in the US, but may be used overseas. This “loophole” involves the addition of “unapproved” sunscreen chemicals without any claims for their activity on the label of the product. This practice makes it important for individuals to review the toxicity profiles of many chemical sunblockers that are used to absorb and disperse UVR. (Table 6.) (see cosmetics-database.com)
Octinoxate Photoallergic tendencies,
Methoxycinnamate Xenoestrogen with interference
of thyroid function and CNS signaling.
Oxybenzone Photoallergic tendencies and common, significant transcutaneous absorption.
Octisalate “Seems safe” but facilitates absorption of other compounds through the skin (carrier properties).
Avobenzene Unstable in sunlight with uncertain end-products. Octinoxate reduces stability of avobenzene in mixtures.
Octocrylene Produces oxygen free radicals when exposed to UVR.
Hemosalate Hormonal activity and may facilitate absorption of herbicides. Metabolized to toxic compounds?
Emsulizole Possible carcinogen that
generates free radicals in
presence of sunlight
PABA/PABA Esters Releases free radicals, xenoestrogens and allergens
Menthyl Anthranilate Releases free radicals,
Mexoryl Poorly absorbed, but unstable in sunlight (about 40% degradation in 2hr).
Sulisobenzone Benzophenone 2 and 4 Irritates skin, eyes and mucus
Membranes, with carrier
properties. May have endocrine
Table 6. Examples of chemical ingredients that are used to block UVR, with their putative toxicity (reference: Environmental Working Group, (EWG, www.cosmetics-database.com) Note these chemical agents are used often in variable combination with incomplete knowledge of their interactions and cumulative biological activity or toxicity.
The data presented in Table 6 may make healthcare givers and consumers think twice in their selection of a popular sunscreen product. Among the most perplexing observations in modern medical literature are the presence “benzones” or related chemicals in the body in more than 90% of the population. A study that analyzed the umbilical cord of ten newborn babies detected an average of two hundred chemicals in newborn blood (EWG, www.cosmeticsdatabase.com). Of considerable concern is the association between the presence of the sunscreen chemicals (oxybenzone) and low birth weight (www.cosmetics-database.com). “The jury remains out” on many synthetic sunscreen chemicals.
Tanning Lamps and Parlors
The quest for a year round tan in industrialized nations has spawned
the “tanning industry”. This industry has tended to imply that “artificial tanning” is safer than natural sunlight tanning. However, it is recognized that the increase in melanin pigmentation in the skin as a consequence of UVR exposure (artificial or natural sciences) is a body defense mechanism against dermal damage1, 10. Tanning lamps often use high intensity UVA light which does not result in natural sunlight tanning in the same manner as sunlight. Furthermore, increases in skin melanin formation during artificial tanning are often preceded by evidence of DNA damage in skin cells1. These observations start to dispel the notion that there is a readily definable “safe level” of UVR exposure.
It is known that tanning achieved with the use of effective topical sunscreens has a greater margin of safety. In this circumstance, modest dosages of UVR reach the skin with the induction of “slower “melanin pigmentation (tanning). This pigmentation protects the skin in a secondary manner leading to the suggestion that modest tanning has an additive protective benefit to the sunscreen (a contrarian thought?). In simple terns, the act of sunbathing without sun- blocking sunscreens may result in more cutaneous damage than is experienced with their use.
If an individual is intent on using a tanning parlor then the routine use of sunscreens is advisable, together with the benefits that can be derived from natural ways to diminish skin damage eg, the use of antioxidants, orally effective sun blockers or protomorphogens for skin repair.
Natural and Optimal Ways to Protect Solar Skin Damage
A general consensus supports the use several techniques (used in a synergistic manner) to minimize exposure to UVR for skin health. However, exposure to the sun is an inevitable and enjoyable life experience for many people. Clearly, this dictates the need to use safe (non-toxic) and effective topical sunscreen products. The use of zinc as a primary sun protective ingredient appears to be an acceptable choice because of negligible toxicity, stability and secondary benefit of zinc on skin structure and function (eg healing tendencies and immune support).
Zinc may be formulated in natural topical creams, lotions or ointments that avoid the use of potentially toxic ingredients, such as oxybenzone. Other natural ingredients that have been recommended for use in sunblocking topical preparation include: minerals, tea polyphenols and coral calcium, but the evidence-base for their use is quite variable. Unfortunately natural agents that are used as sunblockers are not often as cosmetically appealing as synthetic chemicals, but the health conscious may feel that this minor drawback is worthwhile.
The increasingly accepted concept that “beauty or health lies within the body” has stimulated great interest in the use of nutrients, herbals or botanicals that can be given in oral formats (dietary supplements) for cutaneous health, with some significant advantages over topical cosmecuticals 10. The logical approach to creating a safe balance between obligatory sunlight exposure and general health is to use agents that can impact the pathophysiology of solar cutaneous damage. This can be achieved by combining oral and topical agents together. In brief, this combined approach utilizes the use of skin-supporting substances (protomorphogens or building blocks of health skin), antioxidants and DNA-protectors. The use of these nutritional approaches can be amplified by oral agents that have sun-blocking properties when given orally (e.g. Polypodium spp.) .
There are many influences on cutaneous repair. For example, estrogen deficiency in the post-menopause has been correlated with dermal (collagen) thinning that may be corrected in part by topical estrogen (estradiol)1. However, recent research implies that the stimulation of collagen production by estrogen is only observed in skin that has not been repeatedly exposed to sunlight1. The same circumstance may apply to the use of topical progesterone. These finding underscore the difficulty that exists in the reversal of structural skin damage caused by UVR and reinforce the absolute need for comprehensive preventive strategies against cutaneous sun damage 1.
There have been several attempts to examine the evidence-base that exists for the use of dietary supplements in sun protection. An important review of this issue implied that antioxidants, carotenoids and polyunsaturated fatty acids (Omega 3 fatty acids) can prevent sunburn damage). Several studies using nutrients or botanicals have looked at the occurrence of cells that form or accumulate in the skin as a consequence of a minimal erythema-inducing dose of UV radiation (MED) 16, 17.
The value of fish oils (eicosapentanoic and doaasahexanoic acid, EPA and DHA, respectively) in photoprotection has been reported in several studies17, 18. The use of these essential fatty acids is based upon their role in cell membrane formation and their intrinsic anti-inflammatory effects. In brief, the administration of omega 3 fatty acids in relatively high dosages (range 1.8-2.8 grams of EPA an 1.2 plus grams of DHA, requiring up to 10 grams of “regular” fish oil intake) has significant effects on increasing MED of UV radiation17.
Two issues arise in this area of “fish oil therapeutics”. First, compliance is an issue because of dosage requirements, but this may be overcome by using enteric-coated fish oil (targeted-delivery with enhanced bioavailability). Second, liquid peroxidation-end products may occur in UV exposed skin. This oxidation may be countered by the stabilizing influence of antioxidants on fatty acids (e.g. vitamin E). It is prudent to consider the omega 6 to omega 3 fatty acid ratio in the diet of an individual18. An optimal, but perhaps unattainable ratio is 1:1 (omega 6 to 3), but many Western diets provide a ratio of up to 15:1 (omega 6 to 3).
Supplement combinations (synergistic approaches) in sun protection have been studied in a manner ranging from observational to double-blind, parallel, placebo-controlled trials. Such studies highlight the specific value of Vitamin E (d-alpha-tocopherol), Vitamin C retinol, trace minerals, selenium, copper and mixed caretenoids. In some circumstances protective effects, measured by MED, were found to be dose dependent16, 17.
The Natural Anti-Photoaging Protocol
It is possible to create an evidence-based approach to address anti-photoaging. In brief, this would involve factors that are shown in Table 7.
NATURAL ANTIPHOTOAGING APPROACHES COMMENTS
Positive Lifestyle Change Support from many studies and reviewed recently (Null G, Feldman M, Townsend Letter, Oct 2008)19
Sun screening Recreational behavior change, with selection of safe topical sunscreens. Use orally effective sunscreens e.g. Polypodium)
Nutraceuticals An evidence-base for many nutrients (vitamins, minerals, carotenoids and omega 3 fatty acids). Use of vitamin/mineral, fruit, vegetable, berry powder blends, with enteric coated fish oil for, compliance. (www.naturalclinician.com)
Cosmeceuticals Topical antioxidants, protomorphogens etc.
Table 7. A basis for a natural approach to anti-photoaging with emphasis on prevention of sun damage.
It is important to note that a multipronged approach is required in management strategies for photoaging (Table 7.). Change of negative to positive lifestyle is a key initiative combined with avoidance to excessive sunlight exposure.
Nutraceutical and cosmeceutical protection from sun damage or its treatment are a vast area of modern research. At this stage, evidence would support the use of mixed vitamins, minerals and phytonutrient antioxidants (powder blends as a baseline clinical daily prevention strategy (or nutritional insurance). Enteric-coated fish oil can be added (at least 2gm per day, (containing 600mg EPA and 400mg DHA, approximately). The coated and targeted delivery of fish oil to its site of maximal absorption in the small intestine improves bioavailability and compliance (digestive upset, halitosis and “fishy burps”).
Topical cosmeceutical products have variable contents and advantages. Popular ingredients include: Co-enzyme Q 10, polyphenols, physiological lipids for barrier repair, antioxidant vitamins or derivatives (e.g. vitamins or derivatives (e.g. Vitamins A, E and E with Selenium and Zinc), peptides, resveratrol, melatonin and a variety of botanicals.
Matching topical cosmeceutical products to specific clinical circumstance involves complex therapeutic decisions. Perhaps the biggest issue in topical treatments is whether or not the therapeutic agents are absorbed to a degree that can result in benefits. The natural clinician must consider these factors which may be addressed with novel delivery systems including: nanotechnology, liposomes, carrier oils (emu oil) or perhaps safe synthetic transfer agents (if we knew what is readily safe).
Strategies to combat photoaging are key public health initiatives for our “graying” population.
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