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The safety of long-term nicotine use

Discussion in 'The ECF Library' started by rolygate, Feb 5, 2012.

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  1. rolygate

    rolygate Forum Manager Verified Member ECF Veteran

    Supporting member
    Sep 24, 2009
    ECF Towers
    Long-term responsible consumption of nicotine is shown to have negligible effects on health by the Snus data [1]. The NRT data supports this although the volume of data is minuscule in comparison.

    There is plenty of useful info in these blogs, which contain useful references and statements by acknowledged experts and well-known commentators on this subject:

    Public health scientists collaboration:
    Phillips, Rodu:
    Bergen: Tobacco Harm Reduction: News & Opinions
    Laugesen: Health New Zealand
    Phillips: Anti-THR Lies and related topics | because cultivating the truth requires both seeding and weeding
    Nitzkin: Electronic Cigarette Interview with Dr Joel Nitzkin — TobaccoToday

    Nicotine 'addiction'
    Here are some explanations of nicotine's potential for dependence:

    This post about 'addiction' to nicotine clarifies some issues:

    To which it might be added that there is currently no research that reports long-term consumption of small quantities of nicotine is harmful (i.e. additions to the normal dietary consumption of nicotine). We also know that long-term consumption of comparatively large amounts of nicotine is harmless for most people, otherwise the unique national health statistics of Sweden and the 30 years of research data for Snus would not clearly show that the health outcomes for smokers who totally quit or switch to Snus are the same by statistical analysis.

    Individuals, though, may find different. Our experience shows that tolerance to nicotine varies and that some may be advised to limit consumption. In general, it seems that over-consumption of nicotine has indicators that allow the individual to reduce consumption accordingly.

    Also see:

    More explanation of nicotine consumption issues, for a Member who is worried about it:

    Here is an evaluation of the potential elevation of risk with long-term nicotine consumption, written for a Member who had seen clinical studies of nicotine that appeared to suggest there was a serious issue:

    Nicotine consumption in smoking and vaping compared
    Here is a post in which the relative amounts of nicotine consumed by a smoker who switched to vaping are compared. It is useful because it is a concrete example where the figures can be examined.
    Nicotine consumption compared and explained

    Most notably, it seems to show that nicotine consumption is considerably reduced, perhaps by as much as a factor of 2. Another point of interest is that many e-cigarette users - perhaps most, if they were motivated to try - can reduce the amount of nicotine consumed. It appears to be considerably easier to do this than reduce cigarette consumption.

    Nicotine's potential for dependence
    There is no broad agreement on the definition of terms such as addiction and dependence. One differential between the two might, logically, be that addiction could be seen as a strong need to keep consuming a substance that in one way or another may harm the person physically and/or socially (meaning that their life is significantly changed for the worse); dependence would in contrast mean that there is little or no risk of harm from a practical perspective [3], and possibly even some benefits, for some materials.

    Nicotine, in the context of smoking, might be placed in either of those two categories. Nicotine consumption outside of smoking could only be placed in the second category; just like tea drinking, for example.

    See also:

    The evidence for dependence
    There are no clinical trials of (a) nicotine dependence / addiction in human subjects. Not a single clinical study has ever been carried out, as far as we are aware. There are multiple trials of (b) smoking addiction, and (c) nicotine dependence in ex-smokers. It is clear that (b) and (c) are not the same thing as (a). Therefore it cannot actually be stated as fact that nicotine causes dependence. The reasoning is as follows:

    1. If someone is a scientist, or other class of person who intends their statements to be taken seriously as presumably they are based on some sort of evidence, then if that person makes a statement such as "fishheads are addictive", but fishheads are normally only consumed in bouillabesse, and we know beyond doubt that bouillabaisse *is* addictive, then we might reasonably expect that the scientist had access to clinical trials of fishheads that showed they cause addiction independent of bouillabaisse (although as a separate and unrelated issue, it is best not to describe something that is known to be virtually harmless as 'addictive', since that implies harm). Otherwise, we might justifiably assume that it could be any single ingredient or even a combination of the dozens of ingredients that make it 'addictive'.

    2. If the said scientist or other responsible person describes fishheads as 'fiercely addictive', we would no doubt be convinced that they have access to multiple clinical trials that strongly demonstrate that fishheads create powerful dependence in persons who have never eaten bouillabesse; otherwise, we might justifiably conclude the scientist to be nothing more than a fantasist or even a blatant liar.

    3. If we then learnt that not only are there *no* clinical trials that demonstrate reinforcement (potential for dependence), but even multiple clinical trails that showed exactly the opposite (no dependence issues despite large doses for prolonged periods), then we could be justified in believing that the scientist who states such things as fact is not to be believed on anything they say whatsoever, since they have just clearly demonstrated they are either a liar, corrupt, or perhaps just very stupid.

    4. There are no published clinical trials of nicotine dependency issues in never-smokers. There are multiple clinical trials of nicotine administration to never-smokers, for other purposes such as new treatments for disorders, that report specifically that no dependence issues resulted. Therefore the current evidence suggests that nicotine does not cause dependence. It also cannot cause addiction (harmful dependence) since we know from the Snus data that long-term nicotine consumption has negligible effects on health (a Snus consumer is effectively a non-smoker in terms of any measurable effect on health).

    5. Nicotine may cause dependence in animals, but we know that animal nicotine models do not transfer to humans [4].

    6. It is believed that nicotine is not dependence-forming, or has little dependence potential, unless/until (a) it is supplied in cigarette smoke; or (b) - it has been suggested - if repeatedly supplied in large quantities by inhalation (as there are no trials that examined this specific attribute) [6]. The theories are that there is some form of change in brain chemistry for (a), or that (b) repetitive supply of large quantities of many things might cause dependence. Neither of these hypotheses has been tested as nicotine dependence trials in nicotine-naive subjects may have taken place but have not been published. (We now know that such trials do pass ethics committees and therefore can be approved - see [7] ).

    7. Since smoking involves the consumption of a material with 9,600 known compounds (at 2014-03), many of which could be dependence-forming or synergistic with nicotine, it cannot be stated as fact that any single compound in the mix causes dependence. A clinical trial of that compound alone, in naive subjects (those who have never smoked nor taken nicotine supplements) would be required in order to begin to demonstrate this. There are no such clinical studies (that specifically tested for resulting dependence).

    8. As nicotine is a normal and natural part of the diet, many vegetables contain it, and everyone tests positive for nicotine in the bloodstream (in all clinical trials of large numbers of people, all subjects have tested positive), it is reasonable to assume that it is not harmful in dietary quantities; that there may be some sort of effects on the human organism as the material is biologically active and not simply bulk; and that it would be wrong to class it as an 'alien, toxic and dangerous chemical' as is sometimes seen in propaganda. In fact it is clearly more natural to consume it than caffeine (coffee) or alcohol (wine), as neither of these are part of the normal diet.

    So: nicotine has suffered a great deal of propaganda-based attack, due to its conflation with smoking. It is a normal ingredient in the diet, and consuming extra amounts (absent smoking) can be assumed to have similar effects to the same consumption of other dietary ingredients (and this may include increasing levels of harm, as is the case with other dietary ingredients [5] ).
    - It has no dependence potential according to current medical evidence.
    - When combined with the 9,600 currently-identified other compounds in tobacco smoke, dependence on nicotine is known to result.
    - Multiple clinical trials of pure nicotine administered to never-smokers failed to find any evidence for dependence potential, although these trials were for other purposes. This may be how they got past the ethics panels, though it is also necessary to take into account that neither NICE nor the FDA still consider nicotine to be addictive or harmful. NICE PH45 instructs all UK medical practitioners so, and the FDA is removing such cautions on nicotine-containing medicines. They are going gently in this area because there is a great deal of commercial and political pressure to maintain this taboo, but eventually it will be impossible for them to promote nicotine as harmful or addictive as all the evidence tells us it isn't - only the external pressures maintain the illusion.

    In a situation where there isn't a single clinical trial of nicotine that reports dependence (i.e. a trial of pure nicotine administered to never-smokers, of course), and where 30 years of data tells us very clearly that long-term ad lib consumption has no measurable impact on health, and where a veritable mountain of data shows that nicotine is not associated with cancer or heart disease, it will be increasingly difficult to maintain the illusion of significant harm that benefits powerful pressure groups without any evidence for it whatsoever.

    Nicotine tolerance
    As something of a side-note, at ECF we have experienced a factor-10 difference in the individual's tolerance to nicotine. That is to say, what one person finds acceptable may be 10 times too strong or too weak for another.
    Example: an e-cigarette user finds that 6mg (0.6%) strength is the highest that can be tolerated - above this, symptoms of nicotine OD such as dizziness / headache / difficulty in sleeping are experienced.
    Example: an e-cigarette user happily puffs away on 60mg strength (6%) e-liquid, a weaker strength means that cravings are experienced and there is a risk of relapse to smoking; no symptoms of nic OD are seen.

    'Normal' usage profile: the average user employs 18mg (1.8%) or 24mg (2.4%) strength.

    The individual's experience is the only thing that matters: people are so different that one solution does not fit all.


    [1] Snus: there are more than 150 clinical trials and surveys, over 30 years, that in total show Snus is near to harmless at population level, and therefore by implication that extended nicotine use, over decades, is harmless [2]. For a good overview of Snus studies by Foulds et al, from 2003, see:
    For the best large-scale meta-analysis, by Lee, Hamlin 2009, see:
    A review of this study by Rodu 2009:
    A summary of evidence by Lee, Hamling:,f1000m,isrctn

    There are a very small number of individual trials that show other effects (one or two that show a higher instance of cancer of the pancreas, and indeed a couple that show a reduced likelihood of cancer risk elevation, i.e. a protective effect); but since 150 trials say otherwise, such studies are classed as outliers, and it is demonstrated that Snus consumption has no reliably identifiable health impact. The difference between the risk of Snus consumption or total tobacco cessation is statistically insignificant. A Snus user has the same risk as a non-smoker (someone who has totally quit). This is why Sweden has the lowest smoking-related mortality rate of any developed country by a wide margin, and why the smoking deathrate is continually falling toward the percentage reduction in smoking prevalence (a 64% reduction in male smoking prevalence compared to the UK at Q1 2013). But at the individual level, people are so different that an individual must take the best course of action to suit themselves.

    Because this is the only dataset for long-term nicotine use, it was used recently for licensing the extension of NRT use to the long term in the UK. The Snus data was cited (by Benowitz) as the reason why long-term nicotine use is safe. You may find some irony in this - a tobacco product's provable safety being used as the rationale for the safety of a tobacco-cessation product. The NRT safety data exactly replicates the Snus data but is minuscule in size, by comparison (for example NICE say they only have 5 years' data for NRTs). Snus studies have sample sizes in some cases of around 100,000 subjects over multiple decades.

    So we know that long-term nicotine use is safe at population level, because Sweden has many less people dying from smoking than any comparable country, and because the greater part of the evidence shows that health impact from Snus is minimal. As an example, there are numerous citations for the expected lifespan reduction due to long-term Snus consumption of between 2 weeks and 10 weeks; we use a figure of 6 weeks for the expected lifespan reduction from multiple-decade Snus consumption, since it is a median-plus figure and therefore would not be considered an under-estimate. At an individual level, the answer may well be different, because individuals vary.

    [2] Because Snus is a whole tobacco product, with a full spectrum of tobacco ingredients such as all the active alkaloids and not just nicotine, it is incorrect to apply Snus consumption effects to just one of its ingredients. In other words, Snus is known to be acceptably safe, but we don't know what long-term consumption of one item only from the spectrum of ingredients will do. In theory, consumption of one ingredient should have less impact than consuming a material with thousands of ingredients; but logic dictates we cannot say one equals the other.

    [3] Consumption of anything in quantities significantly higher than dietary amounts has a risk. Looking specifically at mild consumer stimulants such as coffee/caffeine, nicotine and alcohol, the long-term effects can be measured. We all know the implications of excess alcohol consumption and it should come as no surprise to learn that excess consumption (whatever that may mean) will, on average, lead to a lifespan reduction. The interesting thing about alcohol is that your cardiologist will tell you to drink a little more wine (as statistically it can be shown to reduce heart issues, when consumed in moderation); while your oncologist will tell you to drink very little or nothing (as statistically it can be shown to promote cancer, above a certain consumption level). It seems that you have to choose which specialist to placate. Significant consumption will, on average, take weeks / months / years off the expected lifespan, as may be expected.

    Coffee must logically be the same, although we don't know by how much it may reduce expected lifespans. It is most unlikely that it does not have such an effect. The Mayo Clinic have recently reported that substantial coffee consumption reduces the lifespan measurably; but then again the Mayo Clinic is measurably inaccurate in its public pronouncements: their ecig-related info is little more than disinformation and propaganda and they have been denounced as liars by experts in the THR area.

    Nicotine is, again, the same, and here we have a little more data: we know that significant Snus consumption, on average, reduces the lifespan by about 6 weeks. We know this because the volume of data on Snus consumers is so vast; and because it is easier to remove confounders from the data than it might be in many other situations (a single Nordic country; a specific consumer product that is not universal; predominantly male consumers; excellent statistics as regards national health / epidemiology; hundreds of clinical studies over three decades). This lifespan reduction may conceivably be the same as or less than for coffee. In other words, we know that significant consumption of nicotine, without smoke, over several decades, has very little negative implication for health (so little that it is statistically very difficult to identify any effect, even with hundreds of thousands of subjects and large cohorts).

    [4] Nicotine trials in animals may show a propensity for nicotine to promote cancer (it cannot cause it since it is not carcinogenic; but in some animals it may assist tumor growth or have similar effects). However we know for certain that this does not apply in humans because there is a vast amount of data from Snus consumption in Sweden that eliminates this possibility. For example, smokers who switch to Snus or who totally quit, on average, have the same health outcomes (a Snus user is essentially a non-smoker in terms of health issues). No cancer-promoting action is demonstrated, and in fact Sweden has the lowest male oral cancer rate in the EU (and of course the lowest male lung cancer rate); no other cancers are seen more often in Snus consumers than non-smokers.

    At one time it was thought that there might be an increased propensity for pancreatic cancer but this turned out to be the result of one clinical study, later shown by Prof PN Lee to be full of errors (much like the 'measles vaccine = autism' faulty clinical study that caused so many problems in the UK and is still doing so now, as the thousands of unvaccinated children due to the scare are now subject to localised measles epidemics numbering hundreds of cases, many hospitalisations of victims, and even deaths). In any event, it is reported that the total incidence of the disease noted was 9 cases, certainly not a clinically relevant number considering the many thousands of subjects, nor a number normally considered statistically relevant; nor a number that might create panic due to its scale. There had been a suggestion that a very small elevation of risk for stroke was also visible by meta-analysis of the Snus studies, but a recent study just on this aspect could not find any association.

    [5] It may be safe to moderately increase the intake of, for example, some vitamins, especially for those who demonstrate a requirement. We know that some individuals may need more of any given dietary ingredient than others. Equally, going past a certain point, taking into account genetic makeup, may be harmful - think vitamin A, vit D, iron, trace elements, fats, etc. Many normal and natural (and vital) dietary ingredients are harmful in excess and can certainly kill. Genetics also come into it, as a diet that suits one may harm another; for example the northern polar peoples traditionally had a diet so high in fat that it would significantly harm others, though it apparently has little effect on them.

    [6] Update Nov 2013: We now have an extensive list of clinical trials where large quantities of nicotine were administered to never-smokers for periods of several months, during clinical trials of nicotine for other purposes (e.g. treatment for certain medical conditions or disorders). No subject subsequently demonstrated any withdrawal symptoms or continued to use nicotine thereafter, despite for example administration of an equivalent amount to 18 cigarettes, daily, for six months, to these never-smokers. None of these trials, though, include large quantities of *inhaled* nicotine. Therefore we can probably say at this point that, "Nicotine does not show any potential for dependence outside of supply within tobacco smoke, although abuse of large quantities of inhaled nicotine has not been tested for so far".

    [7] Update Nov 2013: We now know that ethics committees do permit high-dosage administration of nicotine to never-smokers; not only is this not rare, there are many examples of such trials. Therefore, we need to ask why trial results for nicotine dependence in never-smokers (i.e., a trial of nicotine's potential for dependence rather than a trial of smoking dependence) has never been published. The answer is probably already known, and is not politically or commercially welcome.
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