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20 February 2024
YOU COULD NOT GET A NUTRIENT WITH MORE research validating its benefit than vitamin C. It’s probably one of the most extensively research nutrient with countless studies supporting its benefits for overall health and the skin. However, here I will predominantly focus on how it works on the skin, while just touching on it’s benefits for internal use, which are equally impressive, especially at this time when immune system boosting strategies are even more important.
I will try to cover some common misconceptions about which vitamin C works best on the skin as this is quite a contentious issue. The article is quite long as it covers quite a bit of information, but I know you will appreciate it and please feel free to use parts of it as you see fit for educating your clients. So, let’s dive into some interesting information on this amazing nutrient.
The benefits of vitamin C, whether taken internally or applied topically on the skin are undisputed. When taken internally vitamin C as (L-ascorbic acid) is an extremely powerful antioxidant that is required for healthy tissue growth and repair, adrenal gland function and healthy gums. It protects against the harmful effects of pollution, prevents cancer, protects against infection and enhances immunity, making it one of the most important nutrients to take at this present time. Recommended doses for adults are 1000mgs – 5000mgs depending on age and deficiency.
When it comes to the skin and our appearance vitamin C has several interesting benefits. These include:
Vitamin C as a topical serum first made its appearance in Australia when a famous Vitamin C serum made headlines for its phenomenal lifting effect on the skin. I believe it was on A Current Affair that a 70-year-old man was featured who had applied the famous serum to half of his face and in just eight months the lifting effect was so incredible and it resembled a facelift. The next day David Jones sold over 5000 of these serums instantly. And so, Vitamin C because of the “must-have” skincare product.
White the hero ingredient in the above product was L-Ascorbic acid there are also other forms of vitamin C that I will also discuss, as this is where the issue of what works best can be a little confusing. This is because when it comes to skincare there appear to be two camps of thought – those who advocate that the best form of vitamin C is L-Ascorbic acid (AA), and those who support the lipid-soluble form such as Ascorbyl palmitate (AP), Ascorbyl tetra-isopalmitoyl (ATI) or Sodium ascorbyl phosphate (SAP). So, which one is best? I will attempt to address that later, but first, let’s look at some of the research on the role of vitamin C in the health of the skin and body.
Did you know that vitamin C is a normal skin constituent that is found at high levels in both the dermis and epidermis? In actual fact, the vitamin C content of the epidermis is higher than the dermis, although the vitamin C concentrations in both layers are approximately equal to that of other water-soluble antioxidants, including uric acid and glutathione. Ageing, however, causes a decline in vitamin C content in both the epidermis and dermis as does excessive exposures to UV light or pollutants (e.g., cigarette smoke and ozone) that may also lower vitamin C content, primarily in the epidermis. For this reason, topical application of vitamin C should be part of your skin improvement strategy.
Vitamin C within the skin is normally transported from the bloodstream. Transport proteins specific for ascorbic acid are found on cells in all layers of the skin. Keratinocytes have a high capacity for vitamin C transport, possibly to compensate for limited vascularisation of the epidermis.
Studies now confirm that oral supplementation with vitamin C effectively increases vitamin C levels in the skin. However, when plasma vitamin C levels are saturated, skin vitamin C concentrations no longer increase. At this point, the optimum skin concentrations of the vitamin in the skin are not yet known.
Vitamin C can be provided to the skin through topical application. The stratum corneum is the primary obstacle to efficient vitamin C absorption from external sources; removal of the stratum corneum by laser, chemical, or mechanical methods have been proven to enhances absorption. Although similar studies are still required for humans, studies in laboratory animals show that percutaneous vitamin C absorption greatly depends on pH.
When it comes to ascorbic acid preparations with a pH below 4.0 aid transportation by promoting the uncharged form of vitamin C. Although concentrations of vitamin C up to 30% have been used for animal studies, maximal absorption was achieved with a 20% vitamin C solution, with higher concentrations showing lower absorption. Topical application of ascorbic acid will cross the epidermis into the underlying dermal layers. Therefore 10-20% is proven to provide optimal absorption.
Another important consideration is that the stability of vitamin C in topical solutions is a concern, as exposures to air, heat, and/or light may slowly degrade vitamin C. Although the natural form of vitamin C, ascorbic acid, is the most effective for topical administration, it is the least stable in solution and this is where companies will argue about which formula is most effective.
Symptoms of vitamin C deficiency (known as scurvy) appear once plasma concentrations of the ascorbic acid drop below 10 micromolar (μM), a level that can be prevented by consuming as little as 10 mg of ascorbic acid daily. Cutaneous manifestations of scurvy result from declines in collagen synthesis, leading to disruption of connective tissue and fragility of blood vessels. Early symptoms in the skin include a thickening of the stratum corneum and spots of small subcutaneous bleeding. As scurvy progresses, wound healing is impaired due to the loss of mature collagen, which allows wounds to remain open. Skin lesions caused by vitamin C deficiency are remediated by an adequate intake of vitamin C.
When it comes to photoprotection studies confirm that vitamin C limits the damage induced by ultraviolet (UV) light exposure. Vitamin C is not a “sunscreen” because it does not absorb light in the UVA or UVB spectrum. Rather, the antioxidant activity of vitamin C protects against UV-induced damage caused by free radicals. Vitamin C transport proteins are increased in keratinocytes in response to UV light, suggesting an increased need for vitamin C uptake for adequate protection.
UV light decreases vitamin C content of the skin, an effect that is dependent on the intensity and duration of UV exposure. In cultured keratinocytes, the addition of vitamin C reduces UV-related DNA damage and lipid peroxidation, limits the release of pro-inflammatory cytokines, and protects against apoptosis. Vitamin C also modulates redox-sensitive cell signalling in cultured skin cells and consequently increases cell survival following UV exposure.
In two rodent studies, the addition of ascorbic acid to the diet reduced the size and number of dermal neoplasms and skin tumours induced by chronic UV exposure. To date, no other studies with UV exposure and oral ascorbic acid supplementation in animal models have been published.
In two human studies, oral vitamin C supplementation alone did not significantly increase Minimal Erythemal Dose (MED), a measure of photo-protection from UV light in the skin. Overall, limited data suggest that vitamin C consumption alone provides insufficient antioxidant protection against UV irradiation. However, multiple studies have found that oral supplementation with a combination of vitamin C and vitamin E effectively increases MED and decreases erythema-induced blood flow to damaged areas of skin. Thus, interactions between the two antioxidant vitamins may be necessary to achieve UV protection by dietary means.
Topical application of vitamin C, alone or in combination with other compounds, may result in greater photo-protection than oral supplementation because of the more direct route of administration. In one mouse study, topical application of ascorbic acid delayed the effects of chronic high-dose UVB exposure on the skin, including a reduction in skin wrinkling and the development of skin tumours.
Another study concluded that topical application of vitamin C reduced the number of sunburned cells, decreased erythema response, and reduced DNA damage induced by UVA exposure. Topically applied combinations of vitamin C and vitamin E are more effective in preventing photo-damage than either vitamin alone. In particular, this combination of antioxidant vitamins decreased the immunosuppressive effects of UV exposure, increased MED, and decreased cell damage. Limited human studies are available on photo-protection by topical application of vitamin C. Although topical ascorbic acid reduces radicals in UV exposed human skin, only one study examined its effect on UV-induced erythemal response; this study reported no significant benefit of topical vitamin C. Like animal research, human studies using combinations of vitamin C and vitamin E have documented UV protective effects.
The accumulation of oxidative damage to proteins is a distinguishing feature of both photo-damage (photo-ageing) and intrinsic ageing; such oxidative damage can lead to changes in skin structure. In addition to its antioxidant functions, vitamin C regulates the synthesis of the structural protein collagen. The role of vitamin C in the hydroxylation of collagen molecules is well characterised. Hydroxylation of collagen is necessary for its extracellular stability and support of the epidermis.
In cell culture models, vitamin C supplementation has many beneficial effects in combating photo-damage. Specifically, vitamin C has been shown to stabilise collagen mRNA, thus increasing collagen protein synthesis for the repair of the damaged skin. This occurs concurrently with a decrease in elastin production; the elastin protein is often overproduced in response to photo-damage. Vitamin C also increases the proliferation rate of fibroblasts, a capacity that is decreased with age. Further, vitamin C stimulates DNA repair in cultured fibroblasts.
Human studies often assess skin health by changes in depth or number of wrinkles and by the individual’s perception of skin health. Two observational studies found that higher intakes of vitamin C from the diet were associated with better skin appearance, with notable decreases in skin wrinkling. The use of vitamin C (3-10%) in topical applications for at least 12 weeks has been shown to decrease wrinkling, reduce protein fibre damage, decrease apparent roughness of skin, and increase the production of collagen. Topical vitamin C has also been shown to reverse some of the age-related structural changes in the interface between the dermis and the epidermis. However, the effects of topical vitamin C are not apparent in all individuals, and interestingly, one study found that individuals with high dietary intakes of vitamin C showed no or little additional benefits with a topical administration.
One of the distinctive features of scurvy is poor wound healing, this is because vitamin C levels decrease rapidly at a wound site. Although inflammatory responses often increase free radicals at the site of injury and the presence of vitamin C may limit free radical damage, free radicals may play a complex role in the healing response that is not yet understood. However, the increased demand for dermal collagen synthesis may increase utilisation of vitamin C. Vitamin C may have additional roles in wound healing, for example, by promoting keratinocyte differentiation, stimulating the formation of the epidermal barrier, and re-establishing the stratum corneum.
Studies on the effect of vitamin C supplementation on wound healing have reported somewhat mixed results. Data from laboratory animals and humans show that vitamin C deficiency results in poor wound healing, and vitamin C supplementation in deficient individuals shows significant benefits. Although vitamin C levels appear to increase collagen synthesis and decrease inflammatory responses at the site of the wound, neither vitamin C supplementation or increased plasma vitamin C status increases wound closure time in otherwise healthy individuals. This suggests that vitamin C may only affect specific facets of the wound healing response. Topical ascorbic acid has not been properly evaluated prior to or during wound healing in humans.
Vitamin C is included in oral therapies for pressure ulcers (bed sores) and burns, along with vitamin E, zinc, and other nutritive factors.
Higher intakes of dietary vitamin C have been correlated with a decreased risk of dry skin, suggesting that ascorbic acid may have effects on transepidermal water loss (TEWL). In cell culture models, the addition of vitamin C promotes the synthesis of barrier lipids, which would establish a functioning stratum corneum with low water permeability. One study using topical vitamin C in human subjects correlated its use with decreased skin roughness.
Environmental pollutants, such as ozone, can decrease vitamin C levels in the skin and lead to free radical damage. Smoking also leads to increased wrinkling and decreased collagen synthesis, which corresponds to a decline in plasma vitamin C levels, however, it is unclear if this correlates to lower vitamin C levels in the skin.
Topical vitamin C may be useful against acne to reduce inflammatory lesions. However, studies have primarily focused on the use of sodium ascorbyl phosphate, a synthetic derivative. Topical vitamin C may also have mild skin lightening effects that are caused by reductions in melanin production and melanin oxidation.
As I stated early in this article, let’s take a look at the various forms of vitamin C for topical application and how they differ:
L-Ascorbic Acid (AA) is vitamin C in its purest form. This unstable, water-soluble antioxidant seems to be the key to benefiting from the nutrient’s skin-rejuvenating powers. It is usually found in concentrations of 5 – 25%, though it is arguable what concentration is best for absorption. While some say a 10% concentration boosts collagen synthesis, others say the optimal amount is 20%, and still, others claim that nothing over 18% can be absorbed.
Also important to ascorbic acid’s effectiveness is its pH level. The lower the pH level, the more stable, permeable and, therefore, effective it is. When its pH level is too high, it oxidises, degrades and becomes inactive – or sometimes even a harbour for dangerous free radical formation.
What can be frustrating when seeking for the perfect vitamin C serum is the fact that the ideal, potent formula (high concentration, low pH) tends to irritate the skin. Still, there is a solution: using a topical based cream with no water will be less irritating since most of the inflammation is caused by hydrogen ions generated by acid disassociating in water.
Ascorbic acid is certainly a tricky substance in terms of stabilisation and absorption. And sometimes, even if you do find a formula without water, it can still cause redness or other signs of irritation. Luckily, there are other options to explore for those seeking the advantages vitamin C has to offer.
Synthesised vitamin C derivatives, including ascorbyl palmitate, magnesium ascorbyl phosphate, ascorbyl tetra-isopalmitoyl, tetrahexyldecyl ascorbate, and sodium ascorbyl phosphate are more stable and less irritating than ascorbic acid. The question is, are they more effective? Let’s review what they are:
Ascorbyl palmitate (AP) is a vitamin C ester, which means that it has been esterified to a fatty acid. It is fat-soluble as opposed to the water-soluble ascorbic acid, which may hinder its ability to penetrate the skin. Also, ascorbyl palmitate produces different and long-term effects compared with ascorbic acid.
Magnesium ascorbyl phosphate (MAP) is similar to ascorbic acid in that it is water-soluble. However, it also has what AA lacks: a gentle effect on the skin, efficacy in lower concentrations, and stability at a neutral pH. In one study, researchers discovered that it was statistically more effective than ascorbyl tetra-isopalmitoyl in free radical reduction, although less so than AA. However, it does seem to better quench the deeper layers of skin than ascorbic acid.
Ascorbyl tetra-isopalmitoyl (ATIP) is a vitamin C derivative. It is also stable, due to being fat-soluble and less irritating than ascorbyl acid. Study conduction in 2006 concluded that it ATIP can suppress UV-induced skin pigmentation at a 3% dose. Tetrahexyldecyl ascorbate plays nice with vitamins A and E and UV filters. One study published in Dermatologic Surgery in 2002 showed that a topical formulation combining 10% vitamin C and 7% tetrahexyldecyl ascorbate improved hydration and collagen synthesis in the skin and resulted in “clinically visible and statistically significant improvement in wrinkling” after 12 weeks. Another study conducted in 2009 claimed that it can actually prevent UV damage occurring, and effective at a lower concentration. However, ATIP seems to be a poor performer when it comes to penetrating the skin.
Sodium ascorbyl phosphate (SAP) is known to promote collagen formation, and its ability to be stabilised for at least 24 months if it is stored in the original sealed containers at 25 degrees Celsius. It is also being lauded as an effective acne fighter. Still, it is a fairly new derivative, so there is not a great deal of research comparing it to ascorbic acid.
As you can see there is great value in applying vitamin C topically but here is the crunch. If the vitamin C is Ascorbic Acid or, Magnesium ascorbyl phosphate it will be water-soluble and in order to get it into the skin where we can deliver the benefits it must penetrate through the lipid membrane that acts as an extremely effective barrier. This is where the story becomes interesting as scientists need to overcome this obstacle through advanced delivery systems that will allow the product to penetrate the skin. Then there is the issue of stability and shelf life.
On the other hand, lipid friendly derivatives boast that they can overcome these problems, but are they as effective?
Formulators of lipid-soluble forms of Vitamin C state that extremely low pH of L-Ascorbic Acid can create inflammation, while the ester (lipid-soluble forms) such as Ascorbyl Palmitate, Ascorbyl tetra-is palmitoyl and Sodium ascorbyl phosphate can be applied to the skin without irritation, stinging or burning. Because of these advantages they can be used with glycolic acid and retinol and after laser resurfacing to assist in the recovery process. These are definite advantages. In fact, Ascorbyl Palmitate acts as an anti-inflammatory and can even be applied to conditions such as psoriasis. Studies also show that Ascorbyl Palmitate can dramatically decrease UVB induced erythema (sunburn) when applied topically.
Several years ago, I was fortunate to be working with Professor Michael Roberts from the University of Queensland. Professor Roberts is a Senior Principal Research Fellow, Professor of Therapeutics and Pharmaceutical Science at the University of South Australia and Professor of Clinical Pharmacology and Therapeutics at The University of Queensland. He is also Director of the Therapeutics Research Centre based in the Translational Research Institute at the Princess Alexandra Hospital in Brisbane and in the Basil Hetzel Institute at The Queen Elizabeth Hospital in Adelaide.
He is what you would call a heavyweight when it comes to Clinical Research and in particular in matter that pertain to formulation research. When discussing the issue of which vitamin C was best, he gave me some advice which I will never forget and that it not to get caught up in this debate because there are no simple answers.
He further explained to me that in today’s world there are many pathways that a product can be formulated and stabilised to deliver the desired outcome and vitamin C in a prime example. Overall, studies seem to agree that while ascorbic acid is the champion formulators have to overcome many challenges, namely its ability to penetrate the skin and its lack of stability means that it has a limited shelf life, while in the presence of light it can rapidly deteriorate. Also because of its low pH it often is not easily tolerated in serum form with certain skin types.
This is why we have various formulations that claim that one is superior to another. What you need to know is that applying topical vitamin C is highly beneficial, both in protecting the skin against pigmentation, which is a big issue for us in Australian and in supporting collagen synthesis.
In terms of choosing the best product you need to question the company on a number of issues and request that they provide you with the scientific evidence of the products stability, efficacy and shelf-life, the percentage of active, contra-indications and precautionary measure for their formulation, and what other treatments can it be safely combined with. You will need to look at the research as well as trial the product for yourself. Ultimately, you as the professional will need to make the decision as to which formula offers you the best results that you can trust.
Studies confirm that vitamin C when combined with Vitamin E work synergistically and have a greater affect than when they work on their own. Vitamin E scavenges for dangerous oxygen radicals in the cell membrane, while vitamin C breaks the free radical chain in biological fluid.
Because the body cannot manufacture vitamin C, it must be obtained through the diet or in the form of supplements or, topical application on the skin. However, as Vitamin C is water-soluble most of it is lost in the urine.
Vitamin C is an essential part of skin health both as a small molecular weight antioxidant and as a critical factor for collagen synthesis. Vitamin C contributes to photoprotection, decreases photodamage, and is needed for adequate wound healing. Oral supplementation with vitamin C may help prevent UV-induced damage, especially in combination with supplemental vitamin E.
Dietary vitamin C may also provide photo-protection, but the extent of the protective effects will require additional research. Topical application of vitamin C appears to be an effective route for delivering ascorbic acid to the skin because ascorbic acid appears to be taken up readily at an acidic pH. Despite inconsistencies in vitamin C preparations and study design that examined the effects of topical use of ascorbic acid, the data suggest that vitamin C is most effective in protecting against damage induced by UV light and also has utility in the treatment of photo-damage and/or skin wrinkling.
Lastly, the research confirmed that the greatest effects of Vitamin C supplementation are seen when it is combined with other micronutrients, such as vitamin E and zinc.
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Lopez-Torres M, Shindo Y, Packer L. Effect of age on antioxidants and molecular markers of oxidative damage in murine epidermis and dermis. J Invest Dermatol 1994; 102:476-480.
Shindo Y, Witt E, Packer L. Antioxidant defence mechanisms in murine epidermis and dermis and their responses to ultraviolet light. J Invest Dermatol 1993;100:260-265
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