Collagen and Skincare: Role of Vitamins C, E and B3

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Collagen comprises 75-80% of your skin. It stands to reason, then, that the degradation of collagen contributes handsomely to the visible signs of ageing, and that prevention of this and/or replenishment is a common cosmetic goal. As science has shown us, the jury is out about the power of collagen hydrolysate containing supplements to replenish collagen, while skincare products do not appear to do so. This leaves us with the question: is there any other way to replenish the collagen within your skin? Here we examine the potential of commons trend in the market- skincare products containing vitamins C (± E) and B3. 

Key Points

Keeping in mind the caveat that research into cosmetic skincare is often incomplete, from a rigorous scientific standpoint:

  1. Vitamin C has potential to protect collagen from oxidative damage and is a cofactor to enzymes which synthesise and stabilise collagen. 
  2. There are mixed results regarding the capacity of topical vitamin C to enhance collagen production in actual whole, living human beings. Numerous strategies to enhance its effect have been- and continue to be- explored
  3. It seems that combining vitamins C and E, plus delivery molecules may overcome some issues with bioavailability, and increase antioxidant protection against UV damage. However, in other circumstances, it may not have a desirable effect.
  4. Vitamin B3 in the form of niacinamide is well absorbed into the skin and tolerated, and seems to enhance collagen production and fight ageing, thanks to its conversion to the coenzymes NAD+/H and NADP+/H.

Topical vitamin C and collagen

Vitamin C is often reported as a collagen-protecting nutrient and therefore included in many skincare products. While vitamin C is readily available in the diet through fruit and vegetables, only a small percentage of what enters our gut makes it to the skin thanks to limits on absorption, metabolism and distribution. This may seem to validate the approach of directly slapping it on the skin. 

How would vitamin C cosmaceuticals protect collagen?

Oxidative damage- from UV exposure, pollutants and aging- is a key culprit in the degradation of collagen. In addition to this direct impact, oxidative stress also increases the secretion of certain enzymes (matrix metalloproteinases, MMP’s) which further breakdown collagen. 

Vitamin C has antioxidant properties. In fact, vitamin C and collagen would appear to be a good match: just as collagen is the most abundant protein within the skin, vitamin C is the most abundant antioxidant. It is especially concentrated in the epidermis. Some studies have suggested that topical application of vitamin C may reduce MMP’s. This would seemingly make increasing the vitamin C content of the skin a natural choice. However, we should note that there are limited clinical studies investigating topical Vitamin C. 

Like everything from our microbiome to our chances of getting muscle cramps, our bodies’ synthesis of collagen changes with advancing age. For the worst. That is, it slows down. 

Vitamin C is again thought to come to the rescue here. It is needed by certain enzymes to allow them to produce, as well as stabilise the structure of collagen. It also facilitates the expression of collagen genes, and genes for inhibitors of an MMP.

A brief detour: combinations of Vitamins C + E for collagen

Vitamin E is a fat-soluble antioxidant found within cell membranes (among other places), and acts to protect structures within the membrane from UV-induced oxidation. Vitamin E seems to enhance the antioxidant capacity of vitamin C, while vitamin C replenishes vitamin E stores. Hence the two are often combined in skincare. While small studies are encouraging, larger ones are required to confirm the two vitamins work synergistically.

While a regeneration of vitamin E by vitamin C would certainly be valuable for skin health, it does not necessarily mean vitamin E alone has a direct effect on collagen. Because vitamin E occurs within cell membranes, it is separate from collagen, which is found within the extracellular matrix of skin (i.e. space outside cells that provide structural support to the skin).

So… how well does vitamin C (± E) actually replenish collagen? 

In cell culture studies, vitamin C exposure has increased collagen production. However, we know that such results do not always correspond to real-world benefits. According to some teeny randomised controlled trials (with insufficient statistical power to be taken as proof), using vitamin C-containing products over 3-6 months reduces signs of skin ageing. Some studies suggest they help protect from UV damage. And yet other studies have reported no benefit. Most of the studies showing benefit have used concoctions containing vitamins C and E, together with molecules to assist delivery. (See more about this below). 

It is thought that for any benefit, a concentration of at least 8% Vitamin C is required, while above 20% may cause irritation. Meanwhile, it has been observed that topical application doesn’t increase the vitamin C content of skin if adequate supplies are in the blood i.e. if you’re eating a normal healthy diet with plenty of fruit and veg it’s unlikely to make a difference.  

Research suggests that if vitamin C is to protect against UV radiation, the skin needs to be adequately saturated with it. This is most likely achieved with regular 8-hourly applications. It is also suggested that you apply it after sun exposure as opposed to beforehand, as UV light lowers vitamin C levels of the skin.

The problem of absorption vs collagen replenishment 

If you are going to invest in creams, lotions and potions it may be worth considering that vitamin C comes in different forms. L-ascorbic acid is the one that’s effective in stimulating collagen production. However, in its normal ‘charged’ state, L-ascorbic acid is unstable (i.e. readily breaks down) and doesn’t penetrate the outer layer of skin. This is a problem as you want vitamin C to offer protection and stimulate collagen synthesis throughout the skin for the youthful look. 

A number of strategies have been used in an attempt to get around these issues of stability and absorption. For example, changing L-ascorbic acid to an uncharged form and ensuring its acidity is below pH 3.5 may help. One way of achieving this may be with the addition of ferulic acid (an antioxidant also common in plants)- at least a study on pigs has suggested so. 

I didn’t come across research examining the ultimate impact of ferulic acid and vitamin C alone on skin. However a small study from 2008 showed that application of a product combining 15% vitamin C plus 1% vitamin E with 0.5% ferulic acid did offer protection from UV damage- in a distinct way from sunscreen. In contrast, a small 2020 study showed that it may have a negative impact in the absence of UV radiation. This study used samples obtained from human skin and commercially available products with vitamins C and E, and ferulic acid. Reduced viability of the samples was seen, including a reduced production of collagen by the cells. 

Several other strategies to increase the effect of vitamin C have been or are being trialled. These include using forms of vitamin C which are more readily absorbed into the skin, such as ascorbyl-6-palmitate and magnesium ascorbyl phosphate (MAP). Remembering that any derivatives need to be converted into the active form, L-ascorbic acid, within the body to be effective- it seems these derivatives are unlikely to do so. Disodium isostearyl 2-0 L-ascorbyl phosphate, ascorbic acid sulfate and tetraisopalmitoyl ascorbic acid are among other derivatives used, however their efficacy is still to be proven. 

Use of microspheres, nanoparticles and multilayered microemulsions (such as the combination with vitamin E, or with tyrosine and zinc)  to enhance delivery are also being examined.

Taking anti-ageing efforts a bit further, a number of procedures have been proposed as methods of increasing the penetration of vitamin C. These include electroporation and iontophoresis (which act upon the electrical fields of cells to increase their permeability to molecules), lasers and microdermabrasion. However the research is still in its infancy. While some studies have shown much enhanced delivery of vitamin C, the impact of this on collagen is seldom explored. 

It’s likely that any eventual solution will require a multi-pronged approach.

Potential side effects of topical vitamin C

You should be aware that minor side effects have occasionally been reported with vitamin C application, including yellowing  of skin, patches of pigment loss in hair, staining of clothes, skin stinging, redness or dryness. In addition, there have occasionally also been more serious skin reactions known as urticaria and erythema multiforme. 

Topical vitamin B3 and collagen

Niacinamide is one of the forms of vitamin B3. 

The importance of niacinamide to skin generally has been long known, as deficiency results in pellagra, a disease which includes significant impacts on the condition of the skin. Topical application has since been seen to improve facial texture in humans. A study has compared the effect of using a moisturiser on one half of the face vs the same moisturiser with added niacinamide on the other among 50 caucasuian middle-aged women. During, as well as at the end of the 12 week study period, it was seen that niacinamide provided a variety of beneficial effects, including a reduction in fine lines/wrinkles. 

As collagen degradation is a key factor in the progression of wrinkles, it was hypothesised that increased collagen production accounts for the above changes.

Cell culture studies support this hypothesis: delivery of niacinamide to fibroblasts (the skin’s collagen-creating cells) has been seen to significantly increase collagen content. The collagen:total protein ratio was also increased, which suggests that collagen gets synthesised preferentially.

There are other apparent benefits of niacinamide: it penetrates skin well, is stable, easily formulated and compatible with other ingredients of products, while causing no irritation, redness, burning, stinging or itching. This is in contrast to another form of vitamin B3 (nicotinic acid or niacin), which commonly produces skin flushing (from vasodilation) when added to topical applications. 

The secret to its effect may lie in the fact that the body converts niacinamide to the coenzymes nicotinamide adenine dinucleotide (NAD+/H) and nicotinamide adenine dinucleotide phosphate (NADP+/H). It has been established that there is a reduction in the level of these antioxidant enzymes as we age. Furthermore, the loss of these enzymes has been seen to be ameliorated with delivery of niacinamide- at least in cell cultures of aged human fibroblasts.

More research should be conducted into precisely how NADH and NADPH exert effects on the skin, but their well known capacity to inhibit oxidative stress seems likely. They also have signalling properties which may or may not play a role with collagen. 

The Verdict

A limitation of the body of research in this area of skincare studies are generally of low sample size and a number of questions remain unanswered. Combinations of vitamins C and E, with delivery molecules, may be among the best ways to protect collagen from UV-induced oxidative damage and boost collagen synthesis. Although there is as yet only minimal evidence for this, be aware that it may not be advisable that you use these combinations when away from UV exposure. Future research will hopefully shed more light on this, and how well other strategies of enhancing vitamin C bioavailability work. Products containing niacinamide (vitamin B3) seem to be a safe and effective way to boost collagen levels, likely via antioxidant effects, however additional research would not go astray.

If you've used cosmaceuticals containing vitamins C, E &/or B3, how did they affect your skin?

References

Al-Niaimi, F., & Chiang, N. (2017). Topical Vitamin C and the Skin: Mechanisms of Action and Clinical Applications. The Journal of clinical and aesthetic dermatology, 10(7), 14–17.

Bissett, D.L., Miyamoto, K., Sun, P., Li, J. and Berge, C.A. (2004), Topical niacinamide reduces yellowing, wrinkling, red blotchiness, and hyperpigmented spots in aging facial skin. International Journal of Cosmetic Science. 26: 231-238. doi:10.1111/j.1467-2494.2004.00228.x

Cho S. (2014). The Role of Functional Foods in Cutaneous Anti-aging. Journal of lifestyle medicine, 4(1), 8–16. https://doi.org/10.15280/jlm.2014.4.1.8

Hori, Y., Akimoto, R., Hori, A., et al. (2009) Skin collagen reproduction increased by ascorbic acid derivative iontophoresis by frequent-reversal bipolar electric stimulation. J. Cosmet. Sci.. 60:415–422.

Lee, W.R., Shen, S.C., Wang, K.H., Hu, C.H., and Fang, J.Y. (2003). Lasers and Microdermabrasion Enhance and Control Topical Delivery of Vitamin C. Journal of Investigative Dermatology, 121(5): 1118-1125. https://doi.org/10.1046/j.1523-1747.2003.12537.x.

Levin, J., & Momin, S. B. (2010). How much do we really know about our favorite cosmeceutical ingredients?. The Journal of clinical and aesthetic dermatology, 3(2), 22–41.

Lin, F.H., Lin, J.Y., Gupta, R.D. et al. (2005). Ferulic Acid Stabilizes a Solution of Vitamins C and E and Doubles its Photoprotection of Skin. Journal of Investigative Dermatology. 125(4):826-832, https://doi.org/10.1111/j.0022-202X.2005.23768.x.

Matts, P.J., Oblong, J.E., and Bissett, D.L. (2002) A Review of the Range of Effects of Niacinamide in Human Skin. IFSCC Magazine. 5(4): 285-289

Murray, J.C., Burch, J.A., Streilein, R.D., Iannacchione, M.A., Hall, R.P., and Pinnell, S.R. (2008). A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation. Journal of the American Academy of Dermatology. 59(3):418-425. https://doi.org/10.1016/j.jaad.2008.05.004.

Pullar, J. M., Carr, A. C., & Vissers, M. (2017). The Roles of Vitamin C in Skin Health. Nutrients, 9(8), 866. https://doi.org/10.3390/nu9080866

Romana‐Souza, B, Silva‐Xavier, W, Monte‐Alto‐Costa, A. (2020). Topical application of a commercially available formulation of vitamin C stabilized by vitamin E and ferulic acid reduces tissue viability and protein synthesis in ex vivo human normal skin. J Cosmet Dermatol. 00: 1– 9. https://doi-org.ezproxy.uow.edu.au/10.1111/jocd.13413
Telang P. S. (2013). Vitamin C in dermatology. Indian dermatology online journal. 4(2):143–146. https://doi.org/10.4103/2229-5178.110593

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