[quote][quote]
in contrast to soft "science" of wishfully interpreted statistical correlations from comparisons of self-selected smokers and nonsmokers (which is what the entire antismoking "theory" is built upon) [/quote]
They measured both short and long term AGEs. I don't see the soft science there. [/quote]
The "softness" is due to the fact that the subjects are
self-selected smokers and nonsmokers. With that type of samples you
cannot make causal inference and unfounded attributions of the causality such as: "What is evident is that AGEs are
increased by smoking..."
If all you have are the samples of
self-selected smokers, never-smokers and ex-smokers, then from the
observation of differences, be it of various biochemical variables, or their health or their wealth, you
cannot attribute such differences to some
handpicked parameter, such as smoking. (You can, of course, pick if you wish, but then it is a mere wishful pick, a reflection of your subjective beliefs and not a reflection of some objective causal relation.) Otherwise, with such "science" you could as well "prove" that use of
breathing ventilators shortens the life expectancy of the users (since the correlations here are even stronger), which is precisely the opposite from the actual effect of ventilators on life expectancy -- the ventilators don't shorten the life expectancy but prolong it.
On the other hand, if you start "reinterpreting" your semantics, as you seem to do in your alternating paragraphs, and start claiming that all you really meant with "AGEs are
increased by smoking" was that there is a
statistical correlation, and nothing more, between smoking status and AGEs, than
your position that smoking is harmful to smoker's health
has lost even the pretense of being a scientific fact, since positive correlations can exist between a disease and therapeutic or harmful factors, and you happen to prefer to believe that smokig belongs to the latter factors. It is then basically your personal religion about which there is no point arguing, or for that matter, forcing others to arrange their activities and lifestyles so that universe falls into harmony with your particular religion.
[quote] [quote]
My point is that their conjecture, which is that tobacco smoking results in sufficient AGE quantities to result in effects common with diabetic damage, implies that smoking would accelerate the onset and worsen the symptoms of diabetes [/quote]
I don't think that is implied at all. [/quote]
It certainly is the implication of their hypothesis. If your car went off the road and is sliding down a muddy slope (analogue to diabetes/mud damaging the organism/car's downhill slide) and someone starts rolling logs behind your car down this slope (analogous of smoke glycotoxins producing AGEs leading potentially to similar damage), and you now conjecture that there is an
observable damaging effect of the logs on the car's position, then the implication of your conjecture is that car
ought to slide down faster under the
dual effects of the logs and the mud. My counterpoint to this conjectured 'damaging effect of the logs on car position' was to cite experiments (that was a hard science which can discriminate causal relations), analogous to pointing out that logs can't be moving the way you imagined or doing the conjectured damage since the car is now sliding slower after the logs were deployed, hence moving of the logs must be helping here (e.g. by using them to block the slide), not damaging.
[quote] this is what they are implying:
"Once in the blood stream, glycotoxins
may induce the formation of AGE moieties on both serum and vascular wall proteins and thereby accelerate the development of atherosclerosis."[/quote]
That is much too
simple-minded reasoning about the reaction of complex biochemical networks to
low dose periodic exposure to glycotoxins from tobacco smoke. By that simplistic and mechanistic logic, periodic lifting of weights ought to damage your muscle lifting capacity since you can observe an instantaneous oxidative load and energy depletion in the muscle cells. It's not what happens. The entire biochemical network, in response to these mild periodic loads,
upregulates its energy production and antioxidant capacities. Vaccines works on the same principle applied to the immune network. The
second animal diabetes experiment I cited, indeed shows how this kind of
"exercise effect" arises in the interplay between smoking and diabetes -- a temporary and transient lowering of the insuline sensitivity yields over time to higher insuline sensitivity.
Live organism is not a mechanical device, such as car, and when the gas runs out it remains out of gas, unless someone from outside intervenes. If muscles run out of energy stores, they recharge and then go beyond and beef up the stores for the anticipated larger loads. In other words, the interactions with the external world don't just happen and it is all done with, left behind and forgotten, but rather
interactions are simultaneously learning sessions about the external world so that the
biochemical network can refine its internal model of the external world and
anticipate its behavior and phenomena better in the future interactions.
As already pointed out, what these scientific mercenaries are doing here is a typical
pinhole-view sleight of hand, where they highlight through that pinhole some self-serving tiny fragments of a complex dynamics and exclaim 'see how smoking is doing damage here'. At the same time, they chose to overlook that their 'damage' theory flies in the face of the easily reproducible
plain fact that smoking mice, even under highly unfavorable conditions (including order of magnitude more smoke and absent dosing and rhythms feedbacks) compared to natural, self-dosed and self-paced human smoking,
still lives significantly longer than nonsmoking mice. If smoking had damaging effects on the health of mice as these contractors are conjecturing, than the smoking mice ought to live shorter. Unless, of course, you now decide to redefine the term
"health damage" to include the kinds of "health damage" which makes those
"health damaged" live significantly longer than those who are not "health damaged."
[quote][quote]
Their pinhole presentation of their "theory" (i.e. not putting the quantities of AGE generated via smoking, in a proper perspective, such as comparing them to thousands times greater quantities from foods and beverages), further betrays that they are really playing a rigged game, presumably to please their employer (manufacturer of diabetes drugs). [/quote]
They contrasted it to non-smokers and people with a pathology that is known to cause a significant amount of damaging AGEs. These seem like very satisfactory comparisons to me.[/quote]
As a personal heuristic, that is perfectly fine, of course. But their personal hunch is not a proof or scientific demonstration of anything.
[quote]We do
need to eat food to live; we do not need to smoke to live.[/quote]
(It's amazing that you managed to cram somehow a triple non sequitur in that one little sentence.)
First, one benefit of having the proper perspective (instead of their self-serving pinhole view) on how much glycotoxins->AGEs you get from food per day and how much from 100-200mg of absorbed tobacco smoke matter (from 1-2 packs of cigarettes per day) is that one can then determine how much AGEs you absolutely have take to live and how much is the luxury. If, for example the 100mg of tobacco smoke yields the same AGE excess as one honey roasted peanut, than for your pleasure of that one peanut I might prefer a pleasure of pack of cigarettes. Hence, this is then not a matter life and death, but simply a matter of different preferences.
Their whole antismoking thesis becomes ridiculous in such context i.e. their thesis is merely an imposition of their particular personal preferences for one honey roasted peanut over a pack of cigarettes. The
fact that they chose not to provide the proper context for their "scientific discovery" becomes now more understandable, after the implications of the opposite choice are explored a bit.
The second non sequitur is at the level of basic logic -- the benefits of some activity, such as smoking or eating ice cream, need not be survival in order for the activity to be a
net gain for the person making the choice in the cost-benefit analysis. Smoking can be a net gain for a smoker (read over this thread if you need a reminder what such gains might be), even though it is not required for survival. After all, much of what we choose to do is not based on gains and losses of the order of life and death. Most punishments and rewards are relatively trivial. You can go to a dentist and have him drill your tooth without using novocain. A bit of pain won't kill you (it's actually good for you) and there are possibly downsides to novocain, in addition to a little extra cost. Yet, most people will choose to take the novocain because in their calculation it is a net gain. Ought we not forbid novocain here because it is not really necessary to live?
In short, whether you need something to live or not has absolutely no bearing on whether that 'something' is a net gain in your evaluation or not.
The third non sequitur reveals that the main point of the of the paper (and the debate) was missed entirely. Namely, the "study" seeks to prove hypothesis:
H1) that the observed excess AGEs in smokers are precisely those AGEs produced by the glycotoxins from tobacco smoke i.e. that smoking
causes elevated AGEs in smokers. That was their hypothesis.
The alternative hypothesis is:
H2) that those excess AGEs in smokers are not result of glycotoxins from tobacco smoke but are result of thousands times larger quantities of glycotoxins from food and/or the body's own malfunctioning biochemistry (itself a result of genetic & lifelong environmental factors). The trace amounts of smoke glycotoxins, a mere fraction from the 100 mg of tobacco smoke particles absorbed per pack of cigarettes, are comparatively negligible and have at worst no quantitative relation with the elevated AGEs in smokers they observed, or at best have, via the
'exercise effect' (or vaccine effect),
protective role against the other much larger glycotoxin/AGE contributors. Further, since smoking is protective against diabetes, by virtue of increasing insuline sensitivity over time, this may provide additional protective mechanisms against AGE production or from the damages they produce. Hence smoking is then simply a marker for AGE elevation, protective against AGEs and/or their damage, rather than being a cause of the excess AGEs as the H1 assumes.
In order to assess which conjecture H1 or H2 fits the experimental data better, it is
essential to quantify
all glycotoxic contributions, so one can evaluate which source drives the excess AGEs in smokers, and thus establish whether tobacco smoking is causing these AGEs or whether it protects against them. Since
i) the authors are obviously aware of the need for quantification of all glycotoxic sources before they can compare their effects and decide how to attribute causal roles, and
ii) they chose not to reveal to readers what their figures are for all other glycotoxic sources, and
iii) since their employer's diabetes products compete with overlapping therapeutic properties of tobacco smoke, the more people they can scare away from smoking, the more sales their own diabetes products (and possibly the related anti-AGE products they make) will have.
The most plausible conclusion which follows from (i)-(iii) is that the key data they chose to hide from the readers falsifies their hypothesis H1, supporting thus the alternative H2. Since that is not what their employer wanted to hear or pay for, these poor contractors did what they had to do to earn their keeps -- malign smoking upfront, in general terms at great lengths, hide key data and handwave a tall stack of "maybe's" and "possible's" and "likely's" between the H1 and some rigged, irrelevant measurements shown only through a narrow, carefully delimited pinhole (their rat's tail tendon collagen experiment-like, measurement-like motions).
This entire "study" is thus nothing but a shamelessly transparent pseudo-scientific sham, cooked up by a handful of scientific mercenaries, short on time and creativity, desperately trying to please their heartless pharma employer.
[quote] I think you will also find that many here do watch their dietary sources of AGEs, and do what is needed to prevent unnecessary exposure to AGEs (such as smoking).[/quote]
It still matters how does a pack of cigarettes AGE-compare to things such as one honey roasted peanut.
I should also remind you of the context of this 'how much' glycotoxins argument -- all that discussion makes sense only
if one
grants you, for the sake of argument, those
simple-minded assumptions, which are actually not true at all, of monotonically increasing
harm function with the quantity of glycotoxins and the insensitivity of that curve to the rhythms of exposure, i.e. the
absence of any 'exercise effect'. In fact, for all you or anyone knows, low dose glycotoxic exposure from tobacco smoke, within its larger biochemical content, under the natural feedback controlled pacing and dosing, may well have the "negative harm" range i.e. such form and level of exposure may be a net health gain (as it is the case for so many other aspects of tobacco smoking, discussed throughout this thread e.g. increased glutathione due to low dose oxidative exposure or increased tissue oxygenation and resistance to hypoxic damage due to low dose carbon monoxide,...).
[quote][quote][quote]They didnt come up with the term AGE, it already existed. It is considered a fundamental piece of the puzzle of aging. The aging of the skin is caused mostly by this. This may be why smokers are notorious for having old looking skin for their age. [/quote]
Again confusion of correlations with causation. It is perfectly possible that smoking helps rejuvenate skin, while a "typical" sample of smokers may have older looking skin than a "typical" sample of nonsmokers. [/quote]
Note that my wording implies only correlation with smoking and skin looks. What is evident is that AGEs are increased by smoking, and that they are one of the most important factors of skin aging. [/quote]
You contradict your denial in your very next sentence by declaring causal relation, not just a correlation -- "AGEs are
increased by smoking" . Observing statistical correlations of AGEs on self-selected samples of smokers and nonsmokers cannot demonstrate your claim. Otherwise, one could equally "prove" that use of breathing ventilators decreases the life expectancy. In fact the use of ventilators increases the life expectancy of users, even though the users of ventilators do have lower life expectancy than non users.
Further, the fact that tobacco smoke may carry compounds which result in AGE metabolites, by itself does not mean that smoking
over time will results in
increased AGEs if you take up smoking. For example, tobacco smoke (like anything we metabolize, including food in vastly greater quantities compared to 100mg/pack absorbed) will
deplete some glutathione, yet smoking over time upregulates glutathione by 80% (while transient depletion from smoke is 10% or less). The net effect of smoking is the increased antioxidant and detox capacity of the organism. This is also perfectly analogous to the effect of vaccination -- you introduce a small quantity of an antigen and the net effect is a greater resistance to and quicker elimination of that antigen later, hence lowering of the levels of that antigen in the long run, even though there was transient phase right after the vaccination in which the level of that antigen was elevated temporarily.
The "experiments" in the paper you cited are a piece of antismoking art to behold. They did not measure effects of tobacco smoking at all, but rather the of the
injection of
"aqueous tobacco extracts" and
"cigarette smoke condensate" into the
"rat tail tendon collagen".
Do rats or humans normally smoke with their tail tendon collagens?
That's like trying to prove that daily exercising by lifting 50 pound weights is harmful to humans by tying some poor dog to a bench and dropping a 200 pound weight onto his
tail tendon collagen, then studying a damage to the tail depending on the height of the drop. Wrong quantity, wrong warm up, wrong position, wrong organ, wrong grip, wrong motion, wrong rhythm and repetitions,.... The only relation of such "experiment" with normal weight lifting is that they used some weights. Everything else is transparently rigged to "prove" (to idiots, I suppose) that weight lifting is terribly harmful and painful. And that is the climax of the antismoking hard "science" after 40+ years of "research"? What a shameless scam.
If some gigantic enterprise were to spend 40+ years trying to prove that weight lifting is harmful, spending untold billions of dollars and uncountable human and technological resources, and on the 45th anniversary they do this kind dog 'tail tendon collagen' weight drop experiment as their final "proof", what would you think of it -- is weight lifting really harmful? Wouldn't have they been able to find, with all that money and manpower and technological resources and all these years of hard work, something less ridiculous if there was anything at all, even a tiny, remote whiff of anything at all?
All it would really tell me is that weight lifting must in fact be terrific for your health, if that's how far they got, after all the time and resources they spent trying to prove the opposite. That is precisely what this "experiment", the climax of the antismoking hard "science" as of 1997 proves --
smoking is very, very good for you. Finally, there is your fundamental leap of faith at the root of this branch of argument --
"The aging of the skin is caused mostly by this. This may be why smokers are notorious for having old looking skin for their age." Without proper context (the "pinhole view" problem) this is a
pure religious statement of antismoking faith. What if one honey roasted peanut yields as much AGEs as the smoking of a pack of cigarettes. Than your daily food (the fact that you need some minimum to live is non sequitur) will yield thousands times more AGEs, hence your leap of faith leads to conclusion that basic eating ages us thousands times faster than smoking. And if you drop two honey roasted peanuts from your daily menu, you can smoke two packs per day without any difference in aging. Smoke just one pack, and you are ahead of the evil AGEs.
If you wish to salvage any shred of your argument, bring in a list showing glycotoxic content absorbed by lung cells from a pack of cigarettes, along with glycotoxic loads for some common foods and beverages spanning roughly upper and lower ranges. Without it, you are merely selling your particular religion.
[quote][quote]
Was smoking
the only parameter that varied in those comparisons, such as comparison among identical twins, living in the same environment, working the same job, with one smoking the other not smoking? Alternatively, was smoking parameter
randomized or were these
self-selected smokers, former smokers and non-smokers? Since there weren't human randomized intervention trials in this area (there were only a
handful of such, looking at
lung cancer and
heart disease, all of them
backfired) how is the causal conjecture here any more valid than, say, a hypothetical "study" claiming to "prove" that the
use of breathing ventilators shortens life expectancy -- indeed, the
self-selected sample of current, former and non users of ventilators will certainly be consistent with the conjecture that ventilators shorten the life expectancy, the most of the current users, less for the former users compared to non-users. Yet, the use of ventilators extends the life expectancy. [/quote]
The subjects used in the study were screened for histories of diabetes, hyperlipidemia, and renal and vascular disease, and were required to smoke more than a pack a day during the trial. They also did an in vitro measurement of AGEs on rat tail tendon collagen due to tobacco leaf extract and to smoke. They also measured AGE values via fluorescence measurements. All came up with significant amounts of AGE formation.[/quote]
There is absolutely nothing in this study that connects:
(A) epidemiological correlations of AGEs with smoking in
self-selected samples of human smokers and nonsmokers, with
(B) AGEs induced by "glycotoxins" from tobacco smoke (which is a trace quantity in comparison to the thousands times larger quantities of "glycotoxins" from foods and beverages) or
© AGEs from rat tail induced by injections of their glycotoxic tobacco/smoke extracts.
For example, regarding the © element, they could have taken 100mg of just about any food (equivalent to absorbed tobacco smoke particles from 1 pack of cigarettes), made an extract as they did with tobacco and injected these food glycotoxins into rats tail and they would have obtained similar results as with their tobacco extract injections. The real quantities of food are thousands times larger than the 100mg of smoke particles absorbed from a pack of cigarettes, hence any glycotoxic content of foods (which for some reason they chose not to measure or quantify) will scale proportionately. Since they wished to establish their conjecture that AGEs induced in (B) above cause AGEs observed in (A) above, then
they can't simply ignore the thousands times larger glycotoxic intake from food (that you 'need to eat to live' is irrelevant for the question whether it needs to be measured). The
fact that they did ignore it, and chose not to measure and quantify that much larger contribution as the alternative to their conjectured mechanism (B), indicates that the data went the "wrong" way very dramatically, showing that tobacco smoke glycotoxins contribute negligibly to the body's AGE load in comparison to the food glycotoxins, so they chose to 'take the fifth' on that contribution.
Hence the smoke glycotoxins cannot account for the observed AGE-smoking correlation observed in (A). The other possible explanations is that any particular AGE levels are result of glycotoxic content in foods and the body's antioxidant and detox capacities. This capacity is result of genetic-environmental interaction throughout organism's life, but tobacco smoking upregulates it in any case (e.g. raises glutathione by 80%). People with genetically weaker antioxidant capacity or people exposed to higher glycotoxin levels from foods would thus find the upregulating effect of smoking helpful in reducing the mismatch between their antioxidant capacity and glycotoxic load (this is also supported by animal experiments directly demonstrating protective role of smoking against diabetes, which itself would result in higher glycotoxins and resulting AGEs). With all other parameters evenly and randomly distributed, those with antioxidant capacity adequate to their exposure, would need to smoke less than those with inadequate capacity, hence one would expect to observe correlation (A) if the precise and complete genetic and environmental factors are not controlled (many of which may be unknown presently) so that only smoking is the changed variable between the two groups.
Therefore their statistical correlation (A) is of the same kind as the correlation between the use of aspirin and headaches -- the aspirin users will have more headaches than non-users. In the aspirin-headache analogy, their claim that mouse tail injection experiment proves that higher AGEs correlating with smoking are
caused by tobacco smoke, would be like claiming that aspirin causes headaches by demonstrating that dropping a 10 pound cube of aspirin on a mouse tail shows signatures of pain patterns in their brain MRIs.
If they want to prove causality in animal experiment, why not just have smoking and non-smoking mice and measure the glycotoxic and AGE effects of smoking and nonsmoking directly? We know why -- the smoking mice will live longer and be healthier and happier mice (just look over those
MAOI B figures and graphs, smokers and nonsmokers at different ages, and check against the
mice experiments with long term selegiline use, cited there and you will know the answer). If they want human study that demonstrates causal relation, self-selected samples won't do -- they need to do a
randomized intervention trial, where smokers are randomly selected into a quit group or control group (left alone to smoke). That was done, handful of times only, and the smoking humans, too, live longer and are healthier and happier humans.
Edited by nightlight, 19 April 2007 - 11:10 AM.
