It’s well established that the primary cause of skin ageing is exposure to radiation from the sun. This is perhaps best illustrated by a case report that was published in the New England Journal of Medicine in 2012. A 69-year old man in Chicago had gone to the doctor because the left side of his face was visibly ageing much faster than the right side.
It was eventually determined that the cause was his job. He spent several hours each day driving around in a truck. This resulted in the left side of his face getting much more sun exposure than the right side. Over the course of a few decades, the result was a visibly far more aged appearance on the left side.
Since it’s so well established that solar radiation causes skin ageing, it seems logical to think that sunscreen would be an effective antidote. After all, if the rays that cause skin to age get stopped before they reach their destination, then they shouldn’t be able to cause damage.
But logic isn’t enough. What we really want is evidence. Before we get in to that evidence though, let’s go through some basics. Solar radiation consists of multiple different wavelengths – visible light (the part of the radiation spectrum that we can see with our eyes), infra-red radiation (a.k.a. heat), short wave ultraviolet radiation (UVB), and long wave ultraviolet radiation (UVA). There’s also UVC (ultra short wave), but it’s completely blocked by the atmosphere, so none of it reaches us down here on the surface. Of these, UVB has been found to be primarily responsible for sunburn and skin cancer, while UVA has been found to be primarily responsible for skin ageing.
Back when sunscreens were first developed, their purpose was solely to prevent sunburn, and so they only blocked UVB. Modern sunscreens usually block both UVB and UVA.
The effectiveness of a sunscreen at blocking UVB is categorised with a rating system called SPF (which stands for sun protection factor). The SPF number is the number of times longer it takes for skin to burn (i.e. turn red) when the sunscreen is applied. So an SPF of 20 means it take 20 times longer for skin to burn than would be the case without the sunscreen.
The effectiveness of sunscreen at blocking UVA is usually categorised with either a PFA or a PA rating. PFA is short for “Protection Factor of UVA” and PA is short for “Protection grade for UVA”. PFA is similar to SPF. It’s the number of times longer it takes for skin to tan (i.e. turn brown) when sunscreen is applied. So a PFA of 6 would mean that it takes six times longer for the skin to tan.
The PA rating is basically the same as the PFA rating but is presented in a less immediately understandable format. There are four PA grades, with the lowest being PA+, and the highest being PA++++. PA+ means that it takes two to four times as long for skin to tan, PA++ means it take four to six times as long, PA+++ means it takes eight to 16 times as long, and PA++++ means it takes more than 16 times as long.
Surprisingly, there is only one reasonably large randomised trial of sunscreens as a means to prevent skin ageing in humans. There are however lots of experiments that have been carried out on hairless mice that have generally shown a benefit to sunscreen, and that have been used as a rationale for recommending sunscreen use for people who want to keep looking younger for longer. Mice aren’t humans, obviously, but their skin is similar to ours in terms of how it’s structured and how it functions.
We’ll get to the human trial in a moment, but first we’re going to discuss one of the mouse experiments, to get an idea of what they show. 40 six week old hairless female mice were divided in to four different groups. The first was a pure control group, to which nothing was done. The other three groups were all treated with different substances on their skin and then irradiated with a lamp that emits UVA five times a week for sixteen weeks (which would be equivalent to roughly 16 years if translated in to human terms). The first of these three UV-exposed groups was an active control group. It received a “placebo” sunscreen cream, without any UV filtering substances. The second received a pure UVB sunscreen. And the third received a combined UVB/UVA sunscreen (SPF 20 / PFA 6).
Ok, so what did they find?
Well, I think the picture below says it all. For each of the four groups, it first shows the researcher pinching the skin on a mouse’s back and pulling up as far as possible without lifting the mouse off the floor. It then shows the extent to which the skin has recovered one second later. This gives a measure of skin elasticity, which is a pretty good marker for overall skin age.
The mice who hadn’t been exposed to any UV radiation at all had the most elastic skin at the end of the study, as one would expect. The second best results were seen with the mice who had received the combined UVA and UVB sunscreen. And the worst results were seen with the placebo sunscreen.
The differences in elasticity were large, with the group that received the placebo sunscreen taking an average of 3 seconds for the skin to recover, as compared with less than 1.5 seconds for the group that used the UVB+UVA sunscreen.
So, we have evidence that sun exposure drives skin ageing in humans, and we have evidence from experiments on mice that skin ageing can be decreased to a significant extent by using a broad spectrum sunscreen. But what does the evidence from experiments on humans show?
Like I said before, only a single reasonably sized randomised controlled trial of sunscreen for the prevention of skin ageing in humans exists in the public domain. It was published in the Annals of Internal Medicine in 2013. Funding was provided by the Australian government along with two cosmetics companies (Ross cosmetics and Roche). It’s a shame the cosmetics companies had to be involved since it automatically makes the results more suspect. What is even more suspect is that the study was carried out in the early nineties, but the results weren’t published until almost twenty years later. Why the extremely long wait?
Since the study was carried out before the existence of clinicaltrials.gov (which came on-line in 2000) and other similar sites, and thus the expectation that trials be pre-registered, there is plenty of scope for shenanigans. If the researchers decided to change the supposed purpose of the study (a.k.a. the primary endpoint), or the types of statistical analysis used once the results were in, no-one would be any wiser.
The study was in fact registered at The Australian and New Zealand clinical trials registry, but that happened in 2010, and since the study started recruiting participants in 1992, that’s almost twenty years too late!
If we dig deeper, we find that the original results of the trial were in fact published back in 1999, in The Lancet. The purpose of the original trial wasn’t to see if sunscreens prevent ageing, it was to see if sunscreens prevent skin cancer. Skin ageing was just one of five endpoints studied.
So, although the trial report in Annals of Internal Medicine makes it seem like this was an original trial, this was in fact a secondary analysis of a secondary endpoint in an old trial published more than a decade earlier. This matters, because the evidence value of a secondary analysis of a secondary endpoint is low.
Apart from that, the number of participants in the original trial was 1,400, while the number of participants in the new “trial” was only 900. Where did the other 500 participants go?
Well, the only possible explanation is that the new “trial” is actually a subgroup analysis, i.e. they’re only looking at part of the dataset, not the whole dataset. Why this matters is because it adds further opportunities for manipulation. It’s quite easy to slice your various subgroups in many different ways until you get the result you want. In this particular case they’ve chosen to only include people aged 55 and under in the new trial. What happens when you hit 55? I have no idea, it’s a completely arbitrary age cut-off. So, everyone aged 56 and over has been removed from the analysis.
So what we have here is a secondary analysis of a secondary endpoint in a subgroup of participants from an old randomised trial. And yet, if you read the title and abstract published in Annals of Internal Medicine, you will get the impression that you are reading a primary analysis of a randomised trial. Only if you dig in to the weeds and read the whole study very carefully (which few people do) will you realise what’s actually going on. To me, that’s tantamount to scientific fraud.
The reason the evidence value of this type of secondary analysis is so low is that the researchers have been able to pick and choose what to present and what to hide, and how to analyse their data. There is thus massive scope for bias and manipulation.
Ok, with all that in mind, let’s take a look at the study as presented. So, 903 adults aged 18-55 years old and living in the town of Nambour in Australia were randomised in to two groups. Group one was instructed to put sunscreen on their head, neck, arms, and hands every morning, and again as needed if they were bathing, spending several hours outdoors, or sweating alot. Group two was just told to use sunscreen “as needed”.
Here we immediately run in to another big problem with the trial – it was completely unblinded. This will introduce various biases and confounders. For example, it’s quite easy to imagine that the people who were told to carefully cover themselves with sunscreen every morning became more concerned about sun exposure than the people who weren’t, and that this resulted in them spending less time out in the sun, which could in itself explain any differences in results between the groups.
The provided sunscreen was SPF 15. No UVA protection rating is given (although they do say the sunscreen was “broad spectrum”, so it must have provided at least some protection against UVA as well).
At the start of the study a silicone based replica was created from the skin on the back of the left hand. A second replica was created four and a half years later, at the end of the study, and after that the two replicas were compared under a microscope to see the extent to which skin ageing had occurred. The people doing the work of comparing the two replicas were blinded to group allocation, which is good, since it removes at least one source of bias. A six step scale was used to assess skin age, with a one representing youthful skin that shows no sign of ageing and a six representing maximally aged skin.
At the end of the study, 77% of participants in the sunscreen group reported using sunscreen at least 3 to 4 days a week, as compared with 33% of participants in the control group. So there was a meaningful difference in sunscreen use between the groups.
Ok, what were the results?
Well, that’s not very easy to figure out. The most logical information to provide here would be the proportion of people in each group who progressed from one step on the scale to a later step in each of the two groups. But the researchers don’t give us that. What we get is this ludicrously complicated table from which it’s impossible to draw any conclusions:
When I see something like this, I think that they’re either trying to hide something or they’re just completely incompetent at visualising information in a useful manner. So I’ve helped them to reorganise the information. What we get then is this:
So, there are a few interesting things here. First we see that there is a clear difference in progression between the groups. Overall, 20% of those in the sunscreen group progressed to a later stage over four and a half years, compared with 30% in the control group.
Nerd alert: The p-value of the difference is a little less than 0.01, and it’s possible to debate whether that should be considered statistically significant or not. Usually a p-value below 0,05 is considered “statistically significant”, which would put this well within the bounds of statistical significance. But since this wasn’t the primary endpoint of the original trial, and since this is a subgroup analysis, we need to see a significantly better p-value to believe that there is a real difference.
We can also see in the table that there were some people, a little over 10% in each group, that regressed to an earlier step on the scale. This shouldn’t be possible. Skin ages in one direction, it can’t grow younger. What this shows is the imperfection of the method used to rate the skin, and it should really be viewed as “noise”. If we assume the noise is the same in the upward direction as in the downward direction, then it would mean that it was actually around 20% of participants who progressed in the control group, and 10% who progressed in the sunscreen group. Which would, to my mind, be a pretty good result if it was real.
Let’s take the results at face value and pretend that they actually are real for a second: If the sunscreen decreases the probability of progression over four and a half years from 30% to 20% (or 20% to 10% if we subtract the noise), then that means there is a noticeable difference after this time period in 10% of people. Assuming that the difference between the groups continues to widen over time with continued sunscreen use, which seems reasonable, then that really isn’t bad. After a few decades it would probably be possible to see a meaningful difference in most people using the sunscreen.
Can we take these results at face value though? No, of course not. There’s so much fishy about this study that it’s impossible to conclude that the results say anything about certain what effect sunscreen has on skin ageing. All we can conclude is that they hint at a benefit.
Apart from all that, we don’t really know the extent to which analysis of skin replicas in a microscope correlates with the actual visible ageing that you perceive when you look in the mirror. A better study would have been one where a random sample of people otherwise unconnected with the study would have been asked to guess each participant’s age based on a high resolution photo of the face at the beginning and end of the study. People care more about the visible appearance of their face than what the back of their hand looks like in a microscope.
Ok, let’s wrap up. It’s well established that sun exposure is a major driver of skin ageing. Studies on hairless mice have shown that the ageing effect can be mitigated with sunscreen. However, there is no good quality human data to confirm that the same is true in humans. The only reasonably sized trial in existence is deeply flawed.
With that being said, I think broad spectrum sunscreen use probably does slow skin ageing, based on the fact that we know UV radiation drives ageing, and on the fact that sunscreen has been shown to slow skin ageing in mice.
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