Professor Giovanni Li Volti pictured next to a vape device.

Groundbreaking Study Shows Vaping Far Less Toxic Than Smoking

A replication study has demonstrated that vaping is far less toxic than tobacco cigarettes. 

The study was carried out by Center of Excellence for the acceleration of Harm Reduction of the University of Catania. (CoEHAR). The study is part of the Replica Project, which aims to replicate high quality studies that compare cigarettes with electronic alternatives.

The studies chosen were originally conducted by the tobacco industry, and therefore carry a high risk of bias. To eliminate this risk, studies were replicated by 5 different universities across the world. To minimise the risk of error, each university used three different protocols to measure the toxicity of vapour on human cells.  

In an interview with the Ashtray Blog, CoEHAR Director Professor Giovanni Li Volti explained that the different methods gave the same results, albeit with some minor differences, adding:

…the final message is the same… e-cigarettes and heated tobacco are far less toxic than traditional cigarettes.”

The study also uses open science, making all the data available for other scientists and journalists to read and analyse, a practice still rare in the scientific world. 

Usually scientists do not share the raw data unless asked. But we publish all the results from the Replica Project online, so journalists and scientists all over the world can see the protocol we used, and there is no charge to investigate the statistical analysis.

Giovanni went on to explore the problems that bad science is causing, using the example of a recent study that claimed that vaping causes erectile dysfunction. He believes that many studies that claim vaping is bad for you are on the politically correct side of the debate, and therefore get a lot of media attention, no matter how bad they are. This causes a great deal of harm for public health because it means smokers are misinformed.

90% of current smokers would switch to a less harmful product if they believed it safe, if they were correctly informed. We are now talking about Covid deaths every day in the newspapers, but we have to remember that we have 5,000,000 people dying every year because of tobacco related products.

When it comes to these negative studies, it’s key to look beneath the surface. 

Look at the materials, the methods and the patients – and particularly look at whether the people enrolled in the study have a history of cigarette use. If the answer is yes, the chances are there is a big bias in the study.

Unfortunately we’re still in a situation where doctors and scientists, many of whom are afraid of being associated with the tobacco industry if they recommend vaping, advise smokers to simply quit smoking. But only around 15% of smokers are able to simply quit. That leads to many smokers “dying and getting sick because of an abundance of caution.”

One statement that frustrates Giovanni is the claim that we don’t know how vaping affects people in the long term. In the early days of vaping this was true, and we needed time to find vapers who hadn’t smoked before, and to track the impact of vaping on them over the years. 

Fortunately, thanks to efforts that involved recruiting people across different countries, there is now ten year data on people who vape but have never smoked. The research on this cohort shows that vaping is far less likely to cause respiratory disease than smoking. 

Full Study: Electronic nicotine delivery systems exhibit reduced bronchial epithelial cells toxicity compared to cigarette: the Replica Project

Press Release: No more doubts: e-cigs are less toxic than traditional cigarettes

Full Interview

Can you tell me about the Replica Project? 

As the name suggests, the Replica Project aims to replicate some of the most important studies regarding the comparison between traditional cigarettes and cigarette smoke and electronic devices. Most of the work replicated in this study was performed by the tobacco industry. 

People have been reading the manuscripts provided by scientists in the tobacco industry. They were, of course, afraid of a possible conflict of interest. We wanted to see if we could replicate the studies and see what results we could obtain when the conflict of interest was removed. 

Experiments were replicated in a ring study, meaning that we involved five different laboratories from all over the world. They were; Temple University in the USA, University of Patras in Greece, University of Kragujevac in Serbia, University of Sultan Qaboos in Oman and University of Kazan Rush in Indonesia.

So part of what you’re doing is keeping the tobacco industry honest?

Yes, and that’s also why we involved 5 different universities, to further remove any danger of bias and error by using the wrong protocol. 

The most difficult part of this project was to harmonise all the work in five different countries, with all the pandemic problems and different instruments, and, of course, coordinating the work across five different countries. 

If you were talking to a vaper, or to a smoker who was considering switching from smoking to vaping, what would you say were the most important findings of these studies?

The most important finding comes when you compare a traditional cigarette to heated tobacco or e-cigarettes. You need to compare it with the same amount of nicotine because this is something that is not always considered by a scientist or journalist. You need to make sure you are using the same device. 

You also need to make sure the system is clinically relevant. This means exposing epithelial cells to vapour, as these are the ones which are directly exposed to inhaled toxicants. (The epithelial cells are the ones in the inner layer of the trachea, the bronchial airways.) 

Also, some studies will expose the cells to 500 puffs, which is not clinically relevant. Of course I will get toxicity if I do this, but this is not the experience of vapers.

So I see that you are a vaper. How many puffs are you taking? How many puffs are you doing now – you are not taking 500 puffs – one every second?

So you will want to use a standardised way of exposing cells to your vaping experience. This is the first thing that you should see in a study and this is what we did in the study we replicated.

After we are sure that we are talking about something clinically relevant, we can compare two or three different devices. I can assess that e-cigs and heated tobacco products are 90% less toxic than traditional cigarettes. I don’t smoke anything, but if I was a smoker I would have no hesitation in switching to electronic devices or heated tobacco.

How does that compare to Public Health England estimates of safety (95% safer than smoking)? 

OK, so this is another interesting question. It’s like when you want to measure the length of your kitchen table because your wife decided that it’s time to change it.

We have all experienced this problem, I think, in other areas of life. So there are different ways that you want to measure the space available in order.

To find the right table for your kitchen, you can use a normal metre. You may use a laser, you may use your hands, you know this is 20 centimetres so you can adjust.

It’s the same thing when you want to measure toxicity. There is not a standardised or best method, so the best way is to use different techniques that have different underlying principles in order to make sure that you can replicate the possible toxicity. So this was an advance compared to the previous studies. We decided to replicate the study using a method that is called neutral red uptake.

Neutral red uptake is the standardised method used by the industry and is advised by the FDA and the European Commission in order to provide a toxicity profile update.

This protocol may have biases, like all other protocols, so we added three other methods, each with a different way of measuring toxicity. One is label free, so we’re just measuring electric impedance of the source. If the cells are detaching it’s because they are dying. So if the electricity going through the cells is decreasing we can measure that. So we have a time curve of the toxicity after the exposure to the device or to the electronic cigarette.

Then we use cytofluorimetric analysis that measures cell by cell. So we have a name for each of the cells and I can tell you if each of the cells is alive – if it’s going to die in a few moments, or if it’s completely dead. All these techniques gave the same results.

Of course, I don’t want to be technical in this interview, but I think that the most important message is that different techniques give the same results but with some scientific differences. But the final message is the same, as we were able to confirm – e-cigarettes and heated tobacco are far less toxic than traditional cigarettes. 

So you don’t think the ‘95% safer than smoking’ estimate by Public Health England is an exaggeration?

No. The 5% doesn’t make a big difference. It depends on the technique you are using to measure.

For example, the cytofluorimetric analysis is a very sensitive method. You may arrive at 95% if you use a neutral red, which is still a very good method to assess toxicity but is a little bit less sensitive. 

I give you an average of all the different techniques, so when you see this number you need to always refer to the methods used to measure it. But I think the message is clear. These devices are less toxic than cigarettes.

In the press release you mentioned that only about 80% of the toxicity in cigarette smoke came from non-nicotine elements, so that suggested to me that 20% of the toxicity came from nicotine elements. Is that correct?

The difference is the temperature. The temperature is much higher in the traditional cigarette, and the higher temperatures produce many more toxic compounds in the cigarettes – including nicotine elements. 

Of course, nicotine is not risk free. There is some suggestion it may induce some toxicity. That’s why we can’t consider vaping or heated tobacco risk free. But for sure, it’s much, much less toxic than tobacco smoke.

Of course, the best thing that you can do is not to inhale anything. But if you cannot, of course, the best choice is to switch to vaping or other electronic devices. Also, I’d like to remind my colleagues that people are not dying because of nicotine – but some people are dying and are getting sick because of an abundance of caution.

You don’t stop smoking because of the nicotine, because you like it, because the nicotine gives you satisfaction. So that is not giving you much harm. The problem is the combustible products. But when it comes to vaping, you have 400 fewer toxic compounds. If you want to be more scientific I’m talking about free radicals, nitrates and carbonyls. If we are measuring for these 400 different compounds, they are strongly reduced and these are the compounds that are believed to produce the toxicity from smoking

90% of current smokers would switch to a less harmful product if they believed it safe, if they were correctly informed. We are now talking about Covid deaths every day in the newspapers, but we have to remember that we have 5,000,000 people dying every year because of tobacco-related products.

The problem is almost every day we see a negative story in the media. Yesterday it was vaping damages eyesight, last month it was vaping causes erectile dysfunction. 

That’s the problem. Most smokers would switch to vaping if they were correctly informed. The problem is that some journalists don’t want to investigate properly. And it’s not just journalists but scientists too. Meanwhile, most medical doctors don’t recommend vaping.

If you are obese, your doctor will tell you to go on a diet. If you have high glycemia because you are diabetic, your doctor will give you insulin. If you are addicted to heroin, they might give you methadone – they switch you to a less harmful product.  But if you smoke, they just tell you to quit smoking, like it’s very easy – but it’s not. 

Many of my colleagues are probably not doing this because they are afraid that they will be accused of taking money from tobacco companies. Or they might not do this because they don’t believe or are not informed that these are safer. They are not 100% safe, but they are much, much safer than cigarettes. 

They should be comparing harm reduction to driving. Why do you put your seatbelt on when you are in a car? There’s still risk, but when you have an accident there is a lower probability of you getting harmed. 

Here we are talking about the same principle. You use vaping, or a heated tobacco product, because you reduce the risk. Just like when you put your helmet on when riding a bike, put your seat belt on in the car or use a condom when you have a sexual partner who you don’t know.

You’re developing research standards that can be used by future toxicological studies, and I presume this is because of the variability in results that you’ve seen over the years?

One of the goals of the Replica project, besides of course replicating the study, was to make all this information available. So we are talking about open science.

We went further than this because we are transparent in the interpretation of our results, which is a practice that is not very common. Usually scientists do not share the raw data unless asked. But we publish all the results from the Replica Project online, so journalists and scientists all over the world can see the protocol we used, and there is no charge to investigate the statistical analysis. 

However, given the bias that we’ve seen, which may be implicit or explicit, and which was explored in the E CIG Summit recently, how widely do you think these standards will be adopted, and how significant do you think they will be for future research?

Absolutely, absolutely. Bad science is causing a lot of damage to vaping. A great example is a recent published paper regarding vaping and impotence. This was not a cross-sectional study. I won’t go into the detail, but this is not the way to correctly investigate the impact of disease in our specific group of patients. 

Of course, when they published that paper it got a lot of attention because it’s on the politically correct side of science. When you write that e-cigarettes are toxic, you get a lot of attention. But if you find something that says vaping is less toxic, nobody cares – because it is not on the politically correct side of science. When you are not on the politically correct side of science it’s not pleasant. 

When you have two sides, you have to give voices to both sides, and those voices have to be supported by the evidence. It’s like Novax. There’s a lot of people who don’t want to get vaccinated but there is no scientific basis to the argument you shouldn’t get vaccinated. 

There is no scientific debate based on scientific evidence between people that say these devices are less toxic compared to cigarettes versus people that say these devices have the same risk as cigarettes and so you should not use them. Instead, the second group tells smokers they should quit – as if it was that simple. Maybe only 15% of smokers will be able to just quit. What about the other 85%? They can’t stop smoking, so they will end their lives with lung cancer or cardiovascular disease.

Since your centre started studying vaping, the data on vaping has been growing year on year. How has the growing evidence affected your overall view of the relative safety of vaping, and your confidence in that view?

One of the big issues that people worry about is the impact of vaping over the long term. They always ask, how do you know that vaping in 10, 15 or 20 years will not cause harm. Of course they are not very old devices, so we needed time to check their toxicity. Now, though, we are able to assess a specific population. 

Most of the people who have been involved in previous studies are a population that have smoked for 20 years or more before they switched to electronic cigarettes. Some of these people developed disease, but how do you know if this was the result of 20 or more years of cigarette smoke or of 4 or 5 years of vaping? 

But now we finally have the first studies looking at people who have never used traditional cigarettes but have only ever used vaping devices. That’s the right population to assess. We can measure the toxicity clinically in the long term and these studies can demonstrate they are less toxic in clinics than traditional cigarettes. That’s the correct way to compare vaping/HNB and smoking. 

But isn’t it correct that in terms of long term data, we only have studies looking at people who have used vape devices for four or five years?

In fact, we now have data on these exclusive vapers going back 10 years. One of these studies was directed by Professor Polosa and one is a study called the Deletus Project that is managed inside the Centre of Excellence which I direct here at the University of Catania. 

We’ve been looking at vapers who have never smoked, and of course it’s not easy to collect that kind of population. So we had to involve people from all over Europe in order to put together very strong statistical analysis.

Of course, another issue is that when people start vaping without ever smoking, it causes more opposition. But how do you know these people would have not started smoking anyway? Is that based on scientific evidence? No, it’s just ideology, and I can’t accept that. I mean I have two kids. I hope that they will never use nicotine, but if they have to use nicotine I would be happier if they used an electronic device rather than combustible cigarettes. 

And what about the people who have been vaping for 10 years? What is the evidence telling us?

What we see is a big decrease in associated disease, cardiovascular disease and other lung diseases such as asthma.

Is there anything else you want to add? 

Yes, remember that when it comes to these [negative] studies, you always need to read between the lines. Look at the materials, the methods and the patients – and particularly look at whether the people enrolled in the study have a history of cigarette use. If the answer is yes, the chances are there is a big bias in the study. 

Also, don’t forget there’s a huge percentage of people who are still smoking who would switch if they were correctly informed – so we have to reach those people. If we can, we have a 90% chance of reducing their chances of getting chronic diseases. 

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