At present there are a number of products that claim to combat dermal ageing. The proliferation of products often cause confusion among consumers, who often seek advice from dermatologists for choosing anti-ageing products. In order to provide appropriate suggestions to their patients, dermatologists themselves should be familiar with the products currently available in the market. Thiss article gives an overview on the of role of antioxidants in anti-ageing and how full-fledged monocentric / multicentric trials can help in evaluating the efficacy and safety of anti-ageing products and in making claim substantiation.
Elastosis produces leathery, weather-beaten appearance and are common in people who spend a large amount of time outdoors. As process of ageing occurs Sebaceous glands produce less oil. This can make it harder to keep the skin moist, resulting in dryness and itchiness.
Skin changes which come along with the age are "intrinsic factors". These are obviously natural and inevitable ones. The damage to the skin caused by the environment and our lifestyle are known as "extrinsic factors". These could happen from excessive exposure to UV rays, medication, smoking, stress and several others.
There are seven signs of ageing that become most obvious on the skin.
Appearance of fine lines and wrinkles
Fine lines, crow's feet, wrinkles are evident signs of ageing. As we age, the elastin and collagen fibres, which keeps the skin firm and tight, weaken and the skin appears loose and lax, resulting in fine lines and wrinkles.
Dullness of skin
The glowing skin is replaced by a dull and lifeless one. The top layer of the skin loses moisture due to the ageing process. While young skin renews itself every three to four weeks, older skin takes four to six weeks for renewal.
Uneven skin tone
With ageing, the skin tone becomes uneven at places. This could be because some parts of the skin may contain more melanin than others or with age there is a marked fluctuation in the hormonal levels in a female. Both the factors result in an uneven complexion making the skin look several years older than its actual age.
Dry skin
Healthy skin is radiant and fresh looking because of the natural moisture content in it. But as ageing occurs, it gradually loses the ability to retain moisture and becomes dry and looks lifeless. The older skin has a dry and dehydrated appearance.
Blotchiness and age spots
As the skin thins with age, tiny blood vessels appear and become visible. This makes the complexion uneven and gives a blotchy look. Age spots are usually brown or reddish in colour. They are caused mostly by over exposure to UV rays and become more evident in the ageing skin.
Rough texture of skin
As the skin matures with age, the changes in the texture of skin become noticeable. The skin that was smooth becomes uneven and rough on surface due to layers of dead cells over it.
Visible pores
Otherwise unnoticeable pores become visible with age. This is due to the loss of skin elasticity and sagging.
As skin is drawn down by gravity, pores become more obvious.
During the normal ageing process, skin elasticity and suppleness decrease, and when combined with external factors, cellular damage is enhanced. Many of the external causes of ageing skin are determined by the health and lifestyle decisions made every day. Making unhealthy choices can cause prematurely ageing skin, and this makes people look older, faster.
Following are a few factors which cause early skin ageing.
Stress: There is a direct link between psychological stress and premature ageing. Effects of ageing include skin wrinkles, weakened muscles, eyesight and hearing fade, organ failure, and diminished thinking abilities.
Lack of sleep: Lack of sleep is a major factor in memory loss and symptoms of depression that include low interest in daily activities and negative thinking One of the first places lack of sleep shows up is on the face, with dark circles and bags under the eyes, and sagging skin.
Sun exposure: Unprotected skin that is exposed to the sun becomes more speckled in appearance. Freckles can turn into brown sun spots, the skin takes on a dry, leathery appearance, and wrinkles and sagging increases.
Smoking of cigarettes: Exposure to cigarette smoke significantly increases skin wrinkles and dryness. This is partly due to the behaviour of smoking, and also because cigarette smoke depletes your body of Vitamin C, which is a key ingredient for keeping skin healthy and moist.
Lack of exercise: Living a desk bound life contributes to ageing skin, because exercise helps to tone your muscles and helps in blood circulation.
Exposure to cold weather: Cold winds and low temperatures contribute to ageing skin by making skin dry.
Use of alcohol: Alcohol contributes to ageing skin by dilating small blood vessels in the skin and increasing blood flow near the skin's surface. Over time, these blood vessels can become permanently damaged, creating a flushed appearance and broken vessels on the skin's surface.
Anti-ageing formulation
Anti-ageing formulations are predominantly moisturiser based cosmeceutical skin care products marketed with the promise of making the consumer look younger by reducing visible wrinkles, expression lines, blemishes, pigmentation changes, discolourations and other environmentally (especially from the sun) related conditions of the skin. A comprehensive grading scale for anti-ageing of the skin has been validated and categorizes ageing as: laxity (sagging), rhytids (wrinkles), and the various categories of photoaging, including erythema (redness), dyspigmentation (brown discolourationss), solar elastosis (yellowing), keratoses (abnormal growths), and poor texture.
Anti-ageing formulations usually contain anti-ageing ingredients such as:
Retinol (in the form of retinyl palmitate). In various formulations it has been shown to reduce fine lines and pores.
Epidermal Growth Factor made of five growth factors stimulate cell renewal and collagen production in the skin and strengthen elasticity and structure. In various studies Epidermal Growth Factor has been shown to reduce fine lines, wrinkles and sagging. It also has healing (wounds and burns) and anti-inflammatory properties when applied to skin.
Alpha hydroxy acids (AHAs) and beta hydroxy acids or other chemical peels. These help to dissolve the intracellular "glue" that holds the dead cells together on the skin. The use of this type of product on a daily basis gradually enhances the exfoliation of the epidermis. This exposes newer skin cells and can help improve appearance. AHAs may irritate some skin, causing redness and flaking.
Peptides, such as Argireline (acetyl hexapeptide-3), Matryxil, and copper peptides.
Coenzyme Q10
Anti-oxidants are substances that may protect cells from the damage caused by unstable molecules known as free radicals.
Sunscreens. A high level of UVA protection is recommended as UVA radiation is associated with ageing effects such as wrinkles.
There are various studies which have proven that anti ageing antioxidant products work. Anti-oxidants are what your body uses to slow down ageing and maintain health.
Antioxidants
There are many different types of antioxidants and so-called "free-radical scavengers", which include vitamins C and E, beta carotene, grape seed extract, lycopene, lutein and zeaxanthin, polyphenols and catechins. There are a number of other essential anti-ageing nutrients like Isoflavones, Vitamins B6, B12, Carnosine and Co-enzyme Q10 that can help to slow down, and reduce the effects of, the biological processes of ageing.
Many of these nutrients are also antioxidants but have other essential age-defying properties.
Role of antioxidants in anti-ageing
Antioxidants are found naturally in many fruits, vegetables, and other foods, antioxidants help knock out free radicals (chemical byproducts known to damage cells). When free radicals overwhelm cells, the cells are unable to recover from free-radical-induced damage. Known as oxidative stress, this process is thought to promote ageing. By combating free radicals, antioxidants are thought to fight oxidative stress (and, in turn, produce an anti-ageing effect).
Free radicals destroy collagen and elastin fibres, skin cell lipids, proteins and even DNA structures. In addition, an unhealthy lifestyle based on an unbalanced diet, alcohol consumption and smoking contributes to the assault on skin health and appearance by lowering its natural antioxidant defences, allowing oxidation processes to occur more rapidly. The consequences are the typical signs of ageing, such as dry skin, hyper pigmentation, loss of elasticity and the increasing appearance of wrinkles and furrows. Therefore, the main purpose of anti-ageing products is to increase the anti oxidative potential of the skin. Therefore a broad range of antioxidants, such as vitamins, carotenoids, polyphenols, minerals and fatty acids have gained considerable attention in research. Several studies indicate that the antioxidant potential of the skin might be increased by the use of miscellaneous antioxidants in topical, as well as ingestible, formulations.
Anti ageing antioxidant products are helpful for improving skin tone and reduce wrinkles. While many anti-ageing cosmetic products claim to be effective, many of them simply do not work. At the same time, due to insufficient clarity on claim substantiation, some companies make eccentric claims without scientific data to back them up. This is why it is so difficult to find effective anti ageing skin products in the market. An effective anti-ageing cosmetic product will remove lines, wrinkles and discolouration. It will help skin look years younger.
Anti-ageing antioxidant product development process parallels to drug development process in many ways. It starts from discovery of potential antioxidant molecules to be used in anti-ageing cosmetic product. Various safety and efficacy studies are carried out first in animals; simultaneously in-vitro studies are also conducted. Proof of concept studies evaluating safety and efficacy of anti-ageing cosmetics are carried out in healthy human volunteers, following which full fledged monocentric / multicentric trials are carried out. This is done to evaluate the efficacy and safety of the product and to capture any skin intolerance or irritability caused due to topical application before the product is launched in the market with its anti-ageing claim. These studies are ICH-GCP compliant and studies are conducted as per ICMR guidelines.
Selection of anti-ageing antioxidant molecules
The first step in anti-ageing formulation development should be choosing the most favourable ingredient formulation regarding its optimal bioavailability.
Antioxidants such as beta-carotene or vitamins C and E have been shown to directly neutralize free radicals. Therefore, it is necessary to recognize that, aside from analyzing the particular ingredients used, the final formulation and mixture at least must be tested for true product efficacy and safety. But claims are often based solely on the individual ingredient data and/or traditional use. Furthermore, in vitro data can provide the first indication of ingredient actions, but only placebo-controlled, clinical trials are able to substantiate a proposed health benefit. In an attempt to evaluate the efficacy and safety of useful ingredients and products, it is essential to design double-blind, placebo-controlled, statistically significant, clinical trials to substantiate the efficacy and safety claims.
Designing a clinical trial for anti-ageing antioxidant formulation
The first step is to formulate a hypothesis or a research question. Whether the antioxidant formulation gives anti-ageing effect? A protocol is designed in which primary and secondary objectives are decided on the basis of the research question. The number of volunteers to be included in the study is calculated statistically by a biostatistician.
The study design includes deciding whether two or more anti-ageing formulations are to be compared or a placebo comparative study is to be done or if a new formulation is to be compared with a gold standard. The study can be randomized, double blinded placebo controlled. A case report form, informed consent form and self evaluation questionnaire are prepared to capture data from volunteers. The overall study including protocol and essential documents are approved by the independent human ethics committee prior to start of the study.
The primary objective of the protocol could be to evaluate efficacy of the antioxidant and secondary objective could be to evaluate tolerability of the product. Inclusion and exclusion criteria are decided. Since it is anti-ageing trial , volunteers between age group 35- 55 yrs having wrinkles at crows feet area are preferred. Volunteers with any history of skin ailments, hypersensitive, allergic to chemicals are excluded. Pregnant females and lactating mothers are also excluded.
During screening of the volunteers with inclusion and exclusion criteria the phototype (I, II, III, IV, V) of individual volunteer is also recorded by the expert (dermatologist) on source document. Clinical quotation (Skin Age Score) is recorded by the expert in the CRF. Skin Age Score comprises evaluation of various parameters. Dynamic wrinkles and static wrinkles are scored on basis of the scoring system. Pore severity, pigmentation grading, muscle sag grading and lesion counts are also scored.
Anti-ageing formulation is given to the volunteers as per the randomization sheet where both the investigator and /or clinical researcher and volunteers are blinded to avoid bias. Before dispensing the formulation various other skin measurements are taken using non-invasive instruments.
Instrumental measurement parameters include:
?Pretreatment and post-treatment photography: Photographs of the wrinkles in crows's feet area are taken pre and post treatment to see visible changes or effect of the anti-ageing formulation.
?Skin hydration: Hydration of stratum corneum is measured by instruments like MoistureMeter SC or Corneometer.
?Elasticity and firmness measurement: The Cutometer is a measuring device that helps to estimate the degree of elasticity of the skin. Cutometric measurements are carried out on the cheeks.
?Measurement of depth of wrinkles around crow's feet using 3D in vivo optical measurement of skin : A 3D image analysis system, which allows for fast and highly precise measuring data acquisition. Treated parts of the skin are evaluated for all parameters, e.g. roughness, volumes and dimensions of nasolabial lines, wrinkles or crow's feet scars.
These instruments are generally used to assess efficacy claims. Volunteers are called after a fixed interval for follow-ups till the study duration ends. Readings with the mentioned instruments are taken at baseline, during each follow-up visit and at the end of the study. Accountability of the product, compliance and tolerability is captured during each visit of the volunteer. Adverse events if any are recorded at every visit. Finally data collected is analysed statistically by a biostatistician to see if the results are statistically significant. Thus on the basis of statistical analysis and report the efficacy and safety of anti-ageing formulation is proven. The completed report with data as a backup is sent to the sponsor for claim of their product. Thus not only antioxidants but various other cosmetics, cosmeceutical, dermaceuticals etc can be tested for their efficacy and safety by implementing a well designed clinical trial.
Comprehensive evaluation of anti-ageing formulation requires clear understanding of actives being used, formulation, measurement parameters and interpretation of results which can be done only by experts having comprehensive knowledge of all aspects related to the product, clinical and instrumental evaluation. We at C.L.A.I.M.S Pvt Ltd (Clinical Research Organization) offer safety and efficacy testing services for cosmeceutical, dermaceutical, pharmaceutical and OTC products specifically in the area of skincare, haircare, bodycare and nutraceuticals. C.L.A.I.M.S helps in achieving manufacturing company's needs for product Claim Substantiation by innovative investigation with most modern and unique non- invasive instruments.
Acknowledgement:R.B. Mohile, Promoter and Managing Director,Meena, Head- Clinical Operations & Business Development & Benedict Mascarenhas, Head - Technology & Quality, C.L.A.I.M.S Pvt Ltd.
-The author is Project Manager, C.L.A.I.M.S Pvt Ltd.