[No BS edition] Does e-Cigarette smoke cause cancer? News outlets misleading people again

This is a little different to my usual posts (development, politics), however after reading various news stories that seemed to be making false claims, or otherwise cherry picking parts of the study, I wanted to try to clarify the results from the actual paper.

British news outlets are exaggerating the health risks again

A few friends have sent me various articles showing how e-cigarette smoke causes cancer[1] [2], and many of the articles used rather badly extrapolated claims such as

e-cigarettes might be just as bad as cigarettes

I'm personally questioning whether this kind-of news is funded by tobacco companies to reduce the amount of people switching to e-cigarettes...

I decided to cut the BS and go straight to the study:

E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells - from the Proceeedings of the National Academy of Sciences of the USA (PNAS)

What is in e-juice?

One of the first questions that came to mind, was: what chemical is actually causing the cancer?

E-Juice is a cocktail of several chemicals

• Vegetable Glycerin (VG)
• Propylene Glycol (PG)
• Artificial and/or natural flavourings
• Nicotine, which can range from 0mg (none at all), to 24mg+ per ml (very high). An ex-smoker may use 12mg/ml in "cig-a-like" or starter devices, while those that move onto "mods" can drop down to 3mg or 1.5mg per ml.

All e-juices contain a different ratio and combination of these chemicals. However, most news outlets in the UK were unclear to blame it on a specific chemical. This led me to believe that they never actually understood the study and were just jumping on the hysteria bandwagon.

So what actually is causing cancer?

At first I thought it may be related to Propylene Glycol, which has a rather iffy reputation, despite being classified by the FDA as a safe food additive.

The answer is: Nicotine. So it's not just vaping alone, it's vaping with nicotine which causes cancer.

Nicotine and its nitrosation product
 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone can cause the same 
effects as ECS and enhance mutations and tumorigenic cell transformation 
in cultured human lung and bladder cells. 

Problems with the study

One of the first issues with this study is that it was done on live mice, but only human tissue cells (in-vitro).

Check out this news report on why using animals for these studies is inaccurate. tl;dr; they tested a drug on research animals (most likely mice) which seemed to work great, but in humans... "all six patients who had taken the drug were hospitalized; one is brain-dead". Understanding that mice and humans are not exactly the same, shows how this study could be inaccurate due to the lack of in-vivo testing on humans.

As some may know, claims based off of an in-vitro study are sometimes proven to be false. Taking the carcinogenic metabolites of nicotine and placing them directly into the cells is very clearly going to cause tumour growth. In the human body, there may be a much lower level of those metabolites across the body, and there is of course the immune system to factor in.

Results obtained from in vitro experiments cannot usually be 
transposed, as is, to predict the reaction of an entire organism in vivo

To top it off, the study was performed with a pretty high level of nicotine (for mice).

Mice were exposed to ECS (10 mg/mL, 3 h/d, 5 d/wk) for 12 wk; 
the dose and duration equivalent in human terms 
to light E-cig smoking for 10 y.

10mg/ml isn't exactly "light" for a human. While many ex-smokers may start with 18mg, many lower to 6mg or even 3mg within a few weeks/months. With mice having much smaller bodies and possibly faster metabolisms, 10mg/ml could be equivalent to a human dose of 24mg/ml or higher (which is the kind-of nicotine dose for someone who smokes several packs a day...). I find this dosage concerning. It may have been used to attempt to "simulate" the 10 years of vaping, but at the same time, using a higher dosage could introduce errors into their results.

What causes cancer?

Cancer is generally caused by mutations in a cell which causes it to replicate uncontrollably into a tumour. In some cases these can be caused by genetic defects at birth.

In many cases, the human immune system is capable of fighting many of these tumours naturally, otherwise we'd be getting cancer pretty quickly, given that cells in your body replicate millions of times a day.

This of course brings us back to how they were attempting to artificially re-create 10 years of vaping by increasing the nicotine dosage to something pretty high. As I've just explained, the human body (and other animals) can fight tumours naturally. However, in this study, they were using a high dosage of nicotine to "simulate" 10 years in the span of just 12 weeks.

By using such a high dosage, this would cause a higher rate of genetic defects in a shorter period of time. This means that the mouse's immune system has less time to attempt to fight the tumour growth. Without taking the immune system into account, claims such as "this would cause cancer within 10 years" may be overblown.

Assuming that a human usually vapes less than 10mg/ml, and probably doesn't vape for 3 hours per day (the mice were exposed to 10ml/mg for 3hrs a day, 5 days a week), this could mean a much lower rate of genetic defects, as well as plenty of time for the immune system to attempt to kill the defective cells.

Is it as bad as smoking cigarettes?

Despite what most media outlets seem to be pulling from this paper, the resounding answer is NO.

While the NNAL level in E-cig smokers is 97% lower than 
in tobacco smokers, nonetheless, it is significant 
higher than in nonsmokers

The carcinogenicity of e-cigarette smoke is 97% lower than tobacco. This is with all of the potential flaws that I've explained above. With a higher quality study, possibly with humans, it could be found to be 99% lower than tobacco.

Yes, it may cause cancer (the study was only performed on live mice, and in-vitro human cells, so there is no clear evidence on human subjects), but in no way does this show it being "as bad as cigarettes" as some news articles are claiming.

To clarify these results: using e-cigarettes does NOT cause cancer in itself (as you can get 0mg nicotine juice). BUT, if your e-juice contains nicotine, then you may be increasing your risk (but nowhere near as bad as smoking tobacco).

If you use a vaping device, you can reduce your risk by lowering your nicotine dose, or removing it all together.

GIF Avatar by @stellabelle

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