Yesterday, an email landed in my inbox from someone I have known for many years.
Nathan Jones is one of the owners of Xlear, an American company probably best known for making a rather simple nasal spray. Its original formulation contains just four ingredients: purified water, xylitol, sodium chloride and grapefruit seed extract.
My relationship with Xlear goes back a long way.
For more than two decades, xylitol has wandered in and out of my professional life. I first became interested in it through dentistry, subsequently used it in clinical practice, wrote and lectured about it, and eventually found myself working educationally with Xlear. Over the years they have supported some of my professional activities, and I have come to know several of the people behind the company.
That relationship is worth declaring at the beginning, because this is not going to be an advertisement for Xlear.
Nor, I suspect, is it really going to be a story about xylitol.
Nathan’s email concerned something quite different.
He was frustrated by regulation.
His argument was that changes in European regulation had made it increasingly difficult for products such as theirs to be sold while making meaningful claims about what they might do. He believed the evidential and financial hurdles involved increasingly favoured large pharmaceutical companies over smaller businesses.
I have heard versions of that argument before.
This time, though, I found myself wondering whether I actually understood it.
I didn’t.
And that seemed a much more interesting place to begin.
Evidence is not one thing
Perhaps I stopped because xylitol is not new to me.
I first encountered it seriously more than twenty years ago, at a dental meeting in New York. What began as an interest in dental caries gradually took me much further: into saliva, bacterial behaviour, diet, otitis media, nasal health and, eventually, some rather unexpected conversations about respiratory infection.
Along the way I read the research, incorporated xylitol into clinical protocols, watched patients use it, spoke about it internationally and met some of the researchers and companies involved.
So when Nathan wrote about the difficulties Xlear had encountered in Europe, I already knew there was a body of evidence sitting behind the conversation.
But evidence is not one thing.
A laboratory experiment demonstrating an effect is not the same as a clinical trial. Evidence concerning an ingredient is not necessarily evidence concerning a finished product. A plausible biological mechanism does not establish that something will improve a meaningful outcome in a patient.
Those distinctions matter.
They should matter.
If a company tells us that a product can prevent or treat disease, we should expect evidence appropriate to that claim. Regulation exists, at least in part, to protect us from products whose promises run ahead of their evidence.
And yet Nathan’s email raised a different question.
What happens when evidence does exist, but the system through which it must travel determines what can be said about it?
Crossing the border
The original Xlear nasal spray is remarkably simple.
Purified water. Xylitol. Sodium chloride. Grapefruit seed extract.
Put the bottle on a table in Utah and then put the same bottle on a table in London. Nothing inside it has changed.
The formulation is the same.
The published research has not suddenly become different because the bottle crossed the Atlantic.
And yet something has changed.
For the person using it, that change may be much less abstract.
Imagine someone who has routinely bought the spray in the United States moving to the UK. The product they used yesterday has not changed. Their reasons for using it have not changed. But their ability to find it, buy it, or understand what it is supposed to do may now be different.
From inside a regulatory system, that difference may represent protection. From inside the life of the person using the product, it may simply feel like a barrier.
I became interested in that distance too.
What the company can say about that bottle, how the product is classified, what evidence may be required to support particular claims, and ultimately how it can be presented to clinicians and the public are determined by the regulatory system in which it now sits.
At first glance, that seems entirely reasonable.
Different countries have different rules. Health claims require scrutiny. Consumers need protection. A manufacturer should not be able to turn an interesting laboratory finding into a promise of clinical benefit simply by changing the wording on a label.
But the simplicity of the bottle began to expose the complexity surrounding it.
Imagine that one of its ingredients has been shown to do something interesting in a laboratory.
What can the researcher who conducted the experiment say?
What can I, as a clinician or educator, say when discussing that research?
What can a journalist say about it?
And what can the company selling the product say?
Those questions sound similar.
Legally and scientifically, they may be very different.
Somewhere between an observation in a laboratory and a sentence printed on a bottle, evidence crosses a boundary.
I began to wonder what happens to it there.
A claim worth testing
Nathan has an explanation.
He believes the regulatory environment in Europe has become increasingly difficult for companies such as Xlear to navigate. More importantly, he argues that demonstrating what they would need to demonstrate to make certain health claims could require could require considerable investment in both time and money.
That is quite a claim.
It would be easy to repeat it.
It would also be easy to dismiss it as the frustration of a business owner encountering a regulatory system designed to protect the public.
Neither seemed particularly satisfactory.
What I wanted to know was whether it was true.
What would Xlear actually have to demonstrate to make a particular health claim in Britain?
Could existing research be used?
Would evidence concerning xylitol itself count, or would the finished nasal spray need to be investigated separately?
Would laboratory evidence contribute anything?
Would clinical trials be required?
And, eventually, the wonderfully simple question:
How much would it cost?
I realised that I didn’t know the answers to these questions.
So rather than arguing about the system, I decided to follow the evidence through it.
Evidence in Transit
That is where this investigation begins.
I am not starting from the assumption that Nathan is right. Nor am I starting from the assumption that the regulatory system is wrong.
I want to understand what happens in between.
Over the coming investigations, I will follow the published research and regulatory documents and, where possible, speak with people who understand different parts of the journey.
Xlear provides the first case, but I suspect the questions it raises extend well beyond one company, one product or even xylitol. Ultimately, regulatory decisions are not experienced only by companies. They shape what clinicians can recommend, what patients can access and what the public is told.
Because somewhere underneath this rather ordinary bottle of nasal spray sits a much larger question:
What happens to evidence as it travels through systems?
That is what Evidence in Transit will try to find out.
Next: What exactly would Xlear have to prove?
Before asking whether the regulatory burden is reasonable, we first need to establish what that burden actually is.
What evidence would be required for Xlear to make specific health claims about its nasal spray in the UK and the EU, and how much of the evidence that already exists would count?
Disclosure: I have worked with Xlear in an educational capacity over many years, and the company has supported some of my professional activities. Xlear has no editorial control over Evidence in Transit. Relevant relationships will be declared throughout this investigation.