Pumori Saokar Telang
Consultant Dermatologist, Joshi Hospital Maharashtra Medical Foundation, Jehangir Hospital, Apollo Group, Pune, Maharashtra, India
Consultant Dermatologist, Joshi Hospital Maharashtra Medical Foundation, Jehangir Hospital, Apollo Group, Pune, Maharashtra, India
Address for correspondence: Dr. Saokar Pumori Telang, Embellish, the Skin and Laser Clinic, 1st floor Sangam Project, Opp Air India office, at Sangam Ghat, Wellesley Road, Pune, Maharashtra, India. E-mail: moc.liamg
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Vitamin C is a potent antioxidant drug that can be used topically in dermatology to lớn treat and prevent changes associated with photoageing. It can also be used for the treatment of hyperpigmentation. Because it is unstable và difficult khổng lồ deliver into the dermis in the optimum dosage, research is being directed to lớn find stable compounds of vi-ta-min C và newer methods of delivery of vitamin C into the dermis.
Keywords: Collagen synthesis, depigmentation, drug formulations, L–ascorbic acid, photo-ageing, vitamin C
INTRODUCTION
Vitamin C (Vit. C) is one of the naturally occurring antioxidants in nature.<1,2> Most plants và animals are able lớn synthesise Vit. C in vivo from glucose. Humans & certain other vertebrates lack the enzyme L-glucono-gamma lactone oxidase required for in vivo synthesis of Vit. C;<3> hence, they must acquire it from natural sources such as citrus fruits, green leafy vegetables, strawberries, papaya and broccoli.<3,4> The word “Ascorbus” means no Scurvy. Traditionally, Vit. C-rich foods like lemons were carried by sailors on long journeys to lớn avoid Scurvy, a disease of bleeding gums. In 1937, Dr. Albert Szent Goyrgi was awarded the Nobel Prize for his work in isolating the Vit. C molecule from red peppers and identifying its role in Scurvy.<4>
L-ascorbic acid (LAA) is the chemically active khung of Vit. C. In nature, Vit. C is found in equal parts as LAA & D-ascorbic acid. These are essentially isomeric molecules & are mutually interchangeable.<4> However, only LAA is biologically active và thus useful in medical practice.<2> The absorption of Vit. C in the gut is limited by an active transport mechanism & hence a finite amount of the drug is absorbed despite high oral dosage.<3> Furthermore, bioavailability of Vit. C in the skin is inadequate when it is administered orally.<1,2> The use of topical ascorbic acid is therefore favored in the practice of dermatology.<5>
BIOCHEMISTRY OF vi-ta-min C
Vit. C has a 5-hydrocarbon ring similar lớn that of glucose. With an attached hydrogen ion, LAA becomes a weak sugar acid, similar lớn other alfa hydroxy acids used in dermatology. With a metal ion, it forms a mineral ascorbate. There is a marked interest in synthesis of physiologically active & chemically stable ascorbate molecules as LAA is unstable in nature, especially when exposed lớn light.
MECHANISM OF action OF vi-ta-min C WITH REFERENCE khổng lồ DERMATOLOGY
Vit. C as antioxidant
Vit. C, the most plentiful antioxidant in human skin, forms a part of the complex group of enzymatic & non-enzymatic antioxidants that co-exist lớn protect the skin from reactive oxygen species (ROS). As Vit. C is water soluble, it functions in the aqueous compartments of the cell.<4> When the skin is exposed lớn UV light, ROS such as the superoxide ion, peroxide and singlet oxygen are generated. Vit. C protects the skin from oxidative găng tay by sequentially donating electrons khổng lồ neutralize the free radicals. The oxidised forms of Vit. C are relatively non-reactive.<4> Furthermore, they can be converted back khổng lồ Vit. C by the enzyme dehydro ascorbic acid reductase in the presence of glutathione. Exposure to UV light reduces the availability of Vit. C in the skin.
UV light, reactive oxygen species (ROS) & skin damage - Vit. C và photoprotection
As mentioned above, the exposure of skin to UV light generates ROS.<3> These radicals have a potential lớn start chain or cascade reactions that damage the cells. The harmful effects of ROS occur as direct chemical alterations of the cellular DNA, the cell membrane & the cellular proteins, including collagen.
Oxidative áp lực also triggers certain cellular events mediated by transcription factors such as ROS upgrade transcription factor activator protien-1 (AP-1) that increases matrix metalloprotienase (MMP) production, leading to collagen breakdown.<3> Oxidative bức xúc induces nuclear transcription factor kappa B (NFk
B). This produces a number of mediators that contribute to inflammation và skin ageing.<3> ROS also increase the elastin m
RNA cấp độ in dermal fibroblasts. This may explain the elastotic changes observed in photoaged skin.<2>
Antioxidants are necessary for neutralizing the ROS formed due lớn UV exposure.<2> It is important to chú ý that Vit. C is equally effective against both UVB (290-320 nm) and UVA (320-400 nm).<2,5> Repeated small doses of UVA penetrate 30-40-times deeper into the dermis as against UVB, which mostly affects the epidermis. UVA mutates và destroys collagen, elastin, proteoglycans và other dermal cellular structures.<2> Thus, UVA causes skin ageing and possibly melanoma formation. UVB causes sunburn, ROS, epidermal mutations và skin cancer. Sunscreens when properly applied prevent UV-induced erythema và thymine dimer mutations that contribute khổng lồ cutaneous carcinogenesis. However, sunscreens block only 55% of the miễn phí radicals produced by UV exposure. Photoageing can be prevented by prevention of UV-induced erythema, sunburn cell formation and inducing collagen repair.<2> lớn optimize UV protection, it is important khổng lồ use sunscreens combined with a topical antioxidant. Vit. C does not absorb UV light but exerts an UV-protective effect by neutralizing không tính phí radicals, while this effect is not seen with sunscreens. Under laboratory conditions, it has been shown that application of 10% topical Vit. C showed statistical reduction of UVB-induced erythema by 52% và sunburn cell formation by 40-60%.<3>
Although Vit. C alone can provide photoprotection, it works best in conjunction with vitamin E (Vit. E), which potentiates the kích hoạt of Vit. C four-fold. Hydrophilic Vit. C helps regenerate Vit. E, a liphophilic antioxidant.<1,3,5,6> Thus, Vit. C & Vit. E together protect the hydrophilic & lipophilic compartments of the cell, respectively. Vit. C & Vit. E synergistically limit chronic UV damage by significantly reducing both cell apoptosis and thymine dimer formation.<3,6>
A combination of 0.5% ferulic acid (a potent antioxidant of plant origin) with 15% Vit. C và 1% Vit. E can increase the efficacy of Vit. C eight-fold.<3> It was noted that this triple combination was very useful for the reduction of acute & chronic photodamage, và could be used for prevention of skin cancer in the future.<3>
Vit. C và collagen synthesis
Vit. C is essential for collagen biosynthesis. It has been proposed that Vit. C influences quantitative collagen synthesis in addition lớn stimulating qualitative changes in the collagen molecule.<2> Vit. C serves as a co-factor for the enzymes prolysyl & lysyl hydroxylase, the enzymes that are responsible for stabilizing and cross-linking the collagen molecules.<2> Another mechanism by which Vit. C influences the collagen synthesis is by stimulation of lipid peroxidation, and the sản phẩm of this process, malondialdehyde, in turn stimulates collagen gene expression.<2>
Vit. C also directly activates the transcription of collagen synthesis và stabilizes procollagen m
RNA, thereby regulating collagen synthesis.<2,3> Signs và symptoms of Scurvy, a deficiency disease of Vit. C, are due lớn impaired collagen synthesis. Clinical studies have shown that the topical use of Vit. C increases collagen production in young as well as aged human skin.<3,6>
Vit. C as a depigmenting agent
When choosing a depigmenting agent, it is important lớn differentiate between substances that are toxic lớn the melanocyte & substances that interrupt the key steps of melanogenesis. Vit. C falls into the latter category of depigmenting agents. Vit. C interacts with copper ions at the tyrosinase-active site & inhibits kích hoạt of the enzyme tyrosinase, thereby decreasing the melanin formation. Vit. C also acts on the perifollicular pigment.<5,7,8> However, Vit. C is an unstable compound. It is therefore often combined with other depigmenting agents such as soy and liquorice for better depigmenting effect.<7>
Anti-inflammatory kích hoạt of Vit. C
As stated earlier, Vit. C inhibits NFk
B, which is responsible for the activation of a number of pro-inflammatory cytokines such as TNF-alfa, IL1, IL6 và IL8.<2,3> Therefore, Vit. C has a potential anti-inflammatory activity & can be used in conditions lượt thích acne vulgaris and rosacea. It can promote wound healing và prevent post-inflammatory hyperpigmentation.<2,3>
TOPICAL FORMULATIONS OF vitamin C
Vit. C is available in the market as a variety of creams, serum & transdermal patches. Of these, only the serum contains active Vit. C in an almost colorless form. It is unstable and, on exposure lớn light, gets oxidized khổng lồ Dehydro Ascorbic Acid (DHAA), which imparts a yellow color. The stability of Vit. C is controlled by maintaining a p
H of less than 3.5. At this p
H, the ionic charge on the molecule is removed và it is transported well across the stratum corneum.<3,5,9>
From a clinical point of view, it is important to note that the efficacy of the Vit. C serum is proportional to the concentration, but only up to 20%.<3> The half-life in the skin after achieving maximum concentration is 4 days. A persistent reservoir of Vit. C is important for adequate photoprotection, & can be achieved by regular 8-hourly applications.<1,5> As UV light lowers tissue Vit. C levels, topical Vit. C is best used after exposure to lớn UV light and not prior.<1–3> A combination of tyrosine, zinc & Vit. C has been shown to increase the bioavailability of Vit. C 20-times vis-à-vis using just Vit. C.<2>
A variety of creams with Vit. C derivatives are available in the market. As a dermatologist, it is important lớn know that not all preparations are physiologically effective. Some are not delivered into the dermis in an adequate quantity, while others vì chưng not chemically convert to the biologically active size of Vit. C in the skin.<1,2,4>
Magnesium ascorbyl phosphate (MAP) is the most stable and preferred ascorbyl ester. This lipophilic molecule is easily absorbed into the skin, and the rate-limiting step for absorption is its release from the vehicle, & not the rate of diffusion across the stratum corneum as one might suppose. Map has a hydrating effect on the skin và decreases transepidermal water loss. It is also a không tính phí radical scavenger that is photoprotective và increases collagen production under laboratory test conditions.<1,3> Other useful stable esterified derivatives are:
Disodium isostearyl 2-0 L-ascorbyl phosphate (VCP-IS-Na), another reliable and popular derivative of Vit. C with a C8 alkyl chain attached to the stable ascorbyl moiety. This ensures increased permeability across the epidermis
Tetraisopalmitoyl ascorbic acid, a lipophilic provitamin & sodium ascorbate, are derivatives under research.
ADVERSE REACTIONS OF TOPICAL vi-ta-min C
Topical Vit. C is largely safe khổng lồ use on a daily basis for long durations. It can safely be used in conjunction with other common topical anti-ageing agents such as sunscreens, tretinoin, other antioxidants and alfa hydroxy acids such as glycolic acid. Minor adverse reactions include a yellowish discoloration of the skin, hypopigmented hair and staining of clothes, which occur due khổng lồ oxidative changes of Vit. C. Once applied, Vit. C cannot be fully washed or wiped off the skin. Rarely, stinging, erythema and dryness are observed after use of topical Vit. C. These can easily be treated using a moisturiser. Care must be taken while applying Vit. C around the eyes.<1,2>
Urticaria & erythema multiforme, following the use of topical Vit. C, have been documented.<1> The toxic doses of Vit. C that lead lớn cellular apoptosis under laboratory conditions are 100-200-times the daily recommended dose, giving Vit. C a very high safety profile.<1>
FUTURE DEVELOPMENTS
As Vit. C is hydrophilic, there is a marked interest khổng lồ find methods of efficient transepidermal delivery of the stable active compound. If antioxidants could be delivered in high concentration through the stratum corneum barrier, then a dermal reservoir of protective antioxidant could be increased and thus photoprotection would be enhanced.<5> As stated earlier, the use of stable lipophilic esterified derivatives of Vit. C is being explored for the purpose.<5,8,10–13> Extensive research is underway to lớn investigate microspheres, nanoparticles & multilayered microemulsions for graded topical delivery. Trials have been performed with Vit. C and Vit. E in the same multilayered emulsions together.<6> Both electroporation và iontophoresis have been used to lớn enhance penetration of Vit. C into the dermis.<11,14,15> Application of Vit. C to the treated skin surface after microdermabrasion and CO2 or Er-Yag resurfacing increases the transepidermal penetration of Vit. C 20-times.<2,16> It has also been observed that Vit. C is a good priming agent và a post-operative agent for the prevention of erythema following tia laze resurfacing. Smokers have been found khổng lồ have low Vit. C levels in the dermis, akin to UV-damaged skin. Smoking-related skin ageing is another area where efficacy of Vit. C is being explored. Another very useful application of Vit. C may be striae, where a study has shown that daily application of Vit. C combined with 20% glycolic acid over 3 months can significantly improve striae.<9>
CONCLUSION
To summarize, Vit. C is a naturally occurring drug with multiple desirable effects. With an excellent safety profile, it finds increasing use in photoageing, hyperpigmentation, tissue inflammation & promotion of tissue healing. Ongoing research has been directed toward improving its delivery into the dermis for stimulating collagen production và scavenging không tính tiền radicals. Vit. C thus holds promise as a mainstream drug in future dermatology practice.
The experts have spoken, và this danh mục of vi-ta-min C-spiked serums is sure lớn leave your skin looking healthier và more radiant with each passing day.
The best vitamin C serums are among the most potent skin-care products you can have in your collection for tackling some of the most common skin-care concerns — from dullness and discoloration to lớn fine lines và uneven skin texture. Serums contain the highest concentrations of the brightening ingredient (also known as ascorbic acid or L-ascorbic acid) but there are plenty of other ways to lớn find it, too: in fruits lượt thích oranges & papaya, of course, but also in a slew of other skin-care products like moisturizers, eye creams, và face masks.
"Vitamin C is a potent antioxidant that's a key component khổng lồ many skin-brightening regimens, as it interferes with pigment production & keeps inflammation at bay," explains board-certified dermatologist Joshua Zeichner, MD, the director of cosmetic và clinical research at Mount Sinai’s Department of Dermatology in thủ đô new york City.
Because of its antioxidant properties, vitamin C-enhanced options are also ideal as day serums, since they're well-equipped to lớn protect your skin against any environmental aggressors that you'll experience when you step out of the house. Dr. Zeichner says that vitamin C neutralizes không lấy phí radicals, which are molecules found in external factors lượt thích air pollution và sunlight. This may help protect the skin from pre-cancerous changes due to UV light exposure, he explains. (However, you always still need to lớn wear sunscreen, no matter what you have layered underneath in terms of skin care.) and since không tính phí radicals can speed up signs of aging, vitamin C helps with fending off fine lines they cause, too.
Their help for youthful-looking skin doesn't just stop there though. Because vitamin C is highly acidic, when it's used topically, "the skin is triggered to heal itself by accelerating elastin and collagen production," thành phố new york City-based dermatologist Howard Sobel, MD, previously explained lớn us, which helps lớn plump và firm skin, while preventing premature aging of the skin. Think of it as the ideal daytime counterpart to lớn the retinol or acids you might be using at night to smooth over your skin, tốc độ up cellular turnover, và treat acne scars left over from pesky breakouts.
Another reason why it's always used in brightening products is that vi-ta-min C contains a property that inhibits your skin's melanin production, which is what causes skin discoloration like dark spots và hyperpigmentation, new york City-based board-certified dermatologist Patricia Wexler, MD, previously told trunghocthuysan.edu.vn. Over time, she says that vi-ta-min C can help prevent dark spots from forming in the first place. It's also a
Now that you know what it does, we've rounded up some of the best topical skin-care products containing vi-ta-min C lớn help you achieve glowy skin — và all the rest of those feel-good benefits. Read on for the best vitamin C serums for all skin types that are sure khổng lồ leave you glowing.
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