In the 1950s Denham Harman - whom I met very briefly at a conference in 2003 when he was well into his 80s - proposed the free radical theory of aging. This states that damage to cells and tissue caused by free radicals is a primary cause of the changes that arise with aging.

Free radicals are unstable molecules that are produced by the body as a result of normal metabolic processes, but they can also be introduced into the body through environmental factors such as pollution, UV radiation, and tobacco smoke. These free radicals can cause damage to the cells, leading to aging and disease. To combat this damage the body has a system of antioxidants that work by neutralizing free radicals.

There are two main classes of antioxidants: Enzymes with names like catalase and superoxide dismutase are molecular machines produced by the cell that convert free radicals into harmless substances. The second class of antioxidants is small molecules such as vitamin C and vitamin E which absorb the free radicals preventing them from damaging more important structures.

So, do antioxidants slow skin aging? If this is correct we can make two predictions:

Loss of antioxidants should cause premature skin aging

Increased antioxidants should slow skin aging

For obvious reasons it is difficult to study these questions in humans, however they have been studied in genetically manipulated organisms. There are three forms of the superoxide dismutase enzyme each of which is located in different areas within the tissue. Loss of superoxide dismutase within the mitochondria - the powerhouse of the cell - is lethal early in development, however loss of the forms present between cells or inside the cell does not have a major impact upon lifespan. Interestingly, however these mice did have skin thinning and signs of accelerated skin aging and this was reversed by vitamin C supplementation.

We can’t study the effects of loss of antioxidant enzymes in humans, however we do know that vitamin C deficiency - scurvy - is associated with characteristic skin changes including tiny bruises around the hair follicles, hairs that grow in a spiral “corkscrew” and poor wound healing. Scurvy is rarely seen these days although we do occasionally come across it in elderly patients with very poor nutrition. In any case, scurvy does not lead to premature skin aging and the symptoms are rapidly reversed by vitamin C supplements. Vitamin E deficiency is extremely rare and is not associated with skin changes.

So there is some evidence that loss of antioxidant function can cause skin aging in mice, but does boosting levels in healthy skin prevent skin aging?

Increased levels of antioxidant enzymes in flies led to longer lifespan in naturally short-lived, but not long lived strains of flies. Increased levels of neither the cellular nor the mitochondrial forms of superoxide dismutase increased lifespan in mice.

Linus Pauling - one of a very small number of individuals to win the Nobel prize twice - was later in life an advocate for “megavitamin therapy” i.e. the consumption of very large doses of vitamin C. There is little evidence that this leads to any appreciable health benefits in human and there is also no consistent benefit in mice. However one study of skin aging in a form of mice genetically lacking hair did find a reduction in wrinkle formation with vitamin C supplementation. There was also a reduced rate of skin cancer formation in a genetically predisposed mouse model with topical vitamins C and E.

It is very difficult to study the long term effects of topical antioxidants in humans so we don’t know for sure whether there would be an appreciable impact on skin aging. One study showed that vitamin C and E combined with ferulic acid reduced UV-induced DNA damage in human skin. There is also evidence from a number of studies that vitamin C reduces UV-light induced pigmentation, although it is not so effective in removing pigmentation that is already present.

Ultimately to answer this question definitively what we would need is a long term (at least a decade) randomized study in adults. In the meantime, based on the incomplete evidence that is available my opinions are as follows:-

It is biologically plausible that topical vitamin C +/- E could have some effect in reducing skin aging.

My guess, based largely upon the mouse studies, is that the effects are likely to be at best small and at worst undetectable.

I would not recommend using a vitamin C/E serum unless already using daily sunscreen and a retinol/retinoid.

The form of vitamin C supplementation is important and I will discuss this in a later article.