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The Great Nicotine Myth

Nicotine is one of the last great taboo subjects in the western world, and as a result has some powerful myths attached to it that are unrelated to its actual properties. As a good example of this, most people would be surprised – even amazed – to learn that there is not even a single published clinical trial of nicotine; an extraordinary fact considering the almost-vitriolic description of its ‘addictive’ powers seen occasionally, for which, rather obviously, there is not a shred of evidence. The lack of any published trial despite the intense interest in this subject raises many interesting questions. It also means we do not have the basic evidence to discuss some of the most hotly debated aspects of nicotine.

This does not mean that nicotine is not, for example, dependence-forming; just that a scientist who states categorically that it is ‘fiercely addictive’ or similar, without any evidence, can hardly be regarded as a reliable source – of anything, probably.

The four myths
There are four nicotine myths perpetuated in modern culture that have no basis in fact. These are:

1. The myth of nicotine’s dangerous and alien nature
2. The myth of nicotine’s toxicity
3. The myth of nicotine’s potential for addiction
4. The myth of nicotine’s potential for harm

1. Nicotine – a dangerous, alien chemical?
Hardly. It is a normal ingredient in the diet, everyone consumes it, and everyone tests positive for it.

No person has ever tested negative for nicotine, in any of the large-scale clinical trials that looked at nicotine presence in the population
No one can be shown to have ever been harmed by dietary nicotine
Indeed, it may be beneficial since it is so closely associated with the B vitamin group, has multiple well-recognised beneficial effects, and is commonly investigated as a component in medicines for such conditions as Alzheimers.

All vegetables of the Solanaceae family contain it, and this includes tomatoes, potatoes and aubergines / eggplants. Many foods contain it, including tea: when you drink tea, you are consuming five active alkaloids and nicotine is one of them. After all, that’s why tea works.

Nicotine is closely linked with nicotinic acid, a sister compound that in some organisms is a metabolyte, and both are generally co-located in the same vegetables. You may know it better as vitamin B3 or niacin [1].

There have been several large-scale clinical studies of nicotine presence in humans, the last of which was a test of 800 people by the CDC in the USA: every subject tested positive. Nicotine is a normal, safe ingredient in the diet. Just like any other dietary ingredient some people may require supplementation, and it looks as if about 25% of the population fall into this group.

Vitamin B3 is a necessary component in the diet and a deficiency results in physical and psychiatric symptoms, the most serious of which is pellagra (a serious skin condition resulting in extreme deformities of the skin). B3 assists with cognitive function, memory, work capacity, alertness and stress relief; and so does nicotine.

So nicotine is as normal to consume as vitamin B – unlike alcohol or coffee (caffeine), which are clearly more ‘alien’ as thay are not part of the normal diet and not associated with a vitamin group. Dietary ingredients are not normally considered harmful.

2. Nicotine – a highly toxic drug?
We used to think so – apparently with zero evidence for it, though. Those of us who handle it on a daily basis always knew that it is far less dangerous than supposed, since otherwise – quite simply – many of us would be dead.

In October 2013, Prof Mayer of Graz demolished the myth: he showed that there is no evidence at all for the assumption that nicotine is highly toxic; and in fact the LD50 should be between 10 to 20 times greater than the current figure [2].

His work shows that:

Evidence for the validity of the current LD50 simply does not exist
The method used to arrive at the LD50 is based on a guess made more than a hundred years ago
There is no evidence whatsoever that a dose equivalent to the current LD50 has ever killed anyone
There is overwhelming evidence that doses of multiple times the LD50 have been survived
There is strong evidence that the lethal dose is 4mg plasma nicotine, and this equates to a 500mg – 1,000mg dose.
Therefore it seems logical that a new LD50 for nicotine should be established at around 750mg, which is 12 times the current figure. The current LD50 was simply a convenient addition to the ideological and commercial propaganda surrounding the compound and there was never any evidence for it.

3. Nicotine – a fiercely addictive drug?
Not likely at all; but of course we’d need some sort of evidence either way, and there isn’t any. There is not one single published clinical trial of nicotine.

This is incredible considering the intense interest in this topic, and begs the question: why? In the past it was usually considered that this is because of ethics committee issues; but a more realistic answer is that such trials have taken place but the results could not be published. Such a trial must have taken place before the current era in which ethics committees decide on which trials can and cannot take place; and there are many places in the world where such an issue would not be problematic anyway. We must therefore assume that the results are known but not politically or commercially convenient.

If you are confused by the above (understandably, considering the volume of propaganda) then here are some further explanations:

The only relevant trial is one in which pure nicotine is administered to never-smokers. There is no such published trial.
Administration in a cocktail of 5,300 other compounds [3] is irrelevant (i.e. in tobacco smoke).
Smokers are frequently dependent on nicotine, as a result of smoking. It is assumed that smoking causes some sort of change in brain chemistry. After smoking, people become dependent on smoking, and many become dependent on nicotine.
There are many trials of dependence in smokers, but these are clearly irrelevant.
There is no evidence that nicotine alone can create dependence. Without consumption in tobacco smoke it has no evidence whatsoever for reinforcement (dependence creation).
There is some anecdotal evidence that nicotine administered to never-smokers has little or no dependence-forming capability.

There is a widespread confusion between dependence on smoking and on nicotine. There is no evidence that nicotine, by itself, is ‘addictive’. Because this would be easy to demonstrate, but has not been, we must question the grounds on which beliefs in this area are held. There is clearly a lack of basic science here.

Terminology: addiction vs dependence
Another aspect worth consideration is the terminology related to its potential for reinforcement. The modern preference is to use the term ‘addiction’ for a compulsion to consume or act in a way that will result in harm at some point; ‘dependence’ is used for compulsion to consume or act in a way considered harmless by modern urban living standards.

Thus, smoking, some types of drug use, and gambling compulsion, are considered addictions since there is significant risk of harm of some kind: either physical and/or social. In contrast, the need to drink coffee, although very common today and in some cases quite powerful, is regarded as a dependence since no observable harm results. Such things cannot be harmless since there will always be a cost; but that cost is regarded as insignificant in modern terms.

The consumption of nicotine, by itself, should be classed as a dependence if reinforcement has occurred as a result of smoking, since it is not possible to identify harm – see next section.

Prof Killeen says (to paraphrase him slightly): “Nicotine is not addictive. Administering it together with MAOIs makes it addictive”; and: “People may disagree with me but, since there is no evidence, they have nothing on which to base an argument” [4]. In other words, since there are no clinical trials of nicotine, there is no evidence to argue about; discussion is moot, without evidence.

As he says, people can disagree on (a) whether nicotine is dependence-forming or not, and/or (b) exactly what in tobacco smoke causes the dependence on nicotine to be established. There is plenty of argument about both issues, but until there is some evidence, argument is pointless.

The only thing to go on currently is that anecdotal reports tell us that nicotine administered by itself to never-smokers does not create dependence; and that e-cigarette users, on average, seem able to reduce or even eliminate their consumption of it. This appears to demonstrate an additional factor: nicotine (by itself) does not create tolerance.

This means that it does not require ever-increasing doses for the same effect; indeed, the opposite appears to be demonstrated – e-cigarette users routinely reduce the amount of nicotine they consume, and may transit into a zero-nicotine usergroup, and may cease all ecig use. At any given time 7% of vapers are zero-nic users; this group is continually being refreshed by persons joining by reducing their nicotine intake to zero and persons leaving by quitting totally. We know that this group is generally reported as around 7% in surveys of ecig users; but we don’t know what the figure is for those who join this group per year or who leave (although presumably they are equal).

4. Nicotine – a harmful and damaging drug?
Apart from the facts that:

Nicotine is a normal component of the diet;
And, that everyone tests positive for it;
And, we now know it is between ten and twenty times less toxic than previously argued;
And, that not only is there no evidence for it being dependence-forming, but there is reason to believe it isn’t;
…apart from all that, there could be a valid question that excessive consumption may cause harm. Naturally, this should be examined.

What if we could find a very large number of subjects who have consumed large amounts of supra-dietary nicotine over a lifetime, without smoke, and the data for whom is easily available: multiple very large cohorts with identifiable health data? What if we had national health statistics, a great deal of epidemiology, hundreds of clinical studies, numerous large scale meta-analyses of the studies, and in general a vast volume of data on such persons over many decades?

Well, we do, and it’s called the Snus data [7]. There are hundreds of clinical studies over three decades, together with unique national health statistics (Sweden has the lowest tobacco-related mortality of any developed country by a wide margin).

This huge volume of facts and evidence from Sweden shows that the average reduction of lifespan attributable to lifetime high-volume tobacco and nicotine consumption (without smoke) is only about 4 weeks.

Although there is no isolated data for pure nicotine consumption, indications are it has little risk (for example, from NRT data); and the closest large dataset without inclusion of smoke, the Snus data, shows that harm resulting from consumption of this tobacco is on such a small scale it is hard to identify with any reliability. As examples of this, Sweden has the lowest male lung cancer and oral cancer rates in the EU; the last item contrasts directly with the expectations people might have for an oral tobacco, since Snus has such a low elevation of risk for oral cancer that it cannot even be identified reliably.

Because of the very great size of the data resource, we know there is an average lifespan reduction of around 4 weeks associated with long-term Snus consumption; there are now indications that this may be less than the equivalent in coffee consumption. In addition it can probably be assumed that tobacco consumption involves more risk than nicotine consumption alone, and thus some subtraction from the lifespan reduction figure could probably be made to arrive at a suitable figure for nicotine consumption alone (until we have a 30-year data resource for e-cigarette users, who appear to be the only long-term pure nicotine users on a sufficiently large scale to potentially equal the Snus resource).

You can also see the latest expert medical position on nicotine’s potential for harm from materials supplied by the UK’s NICE, in their direction to doctors on this topic [5]; and from other experts in this area such as CV Phillips and B Rodu: nicotine does not cause cancer, is not associated with cancer, does not promote cancer, and is not associated with heart disease .

There is probably no other subject surrounded by so much myth and propaganda as nicotine. The reasons are multiple and complex, and comprise ideology together with commercial, economic, political and social pressures.

Nicotine is a relatively harmless normal dietary component that many people appear to need to supplement. Because the required dietary supplementation was normally supplied in a lethal cocktail of smoke, it became tainted by association, and only because of that. No one considers the consumption of ketchup to be an addictive behaviour, and ketchup contains significant amounts of nicotine; no one considers it a bad idea to feed their baby mashed-up vegetables, which of course contain nicotine. You feed your baby nicotine and no one has ever suggested this is a bad idea – because it isn’t.

If people wish to consider supplementary nicotine consumption undesirable, then they must apply the same logic to coffee, tea, sherry, wine, beer, and perhaps chocolate – or risk being classed as a gold-plated hypocrite. Then, consumption of vegetables such as potatoes and tomatoes would need to be carefully limited or avoided, and this would probably lead to multiple nutritional deficiencies.

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