Article-Journal Review Commentary 1)
To the editor: Domino et al. (Aug 5 issue)2) suggest that nicotine obtained from the consumption of vegetables could complicate the interpretation of studies of exposure to environmental tobacco smoke based on the detection of nicotine or its metabolite cotinine. The crux of their argument was that typical levels of vegetable consumption could result in an exposure to nicotine equivalent to that from inhalation of air with a “low concentration of nicotine from tobacco smoke”. In fact, exposure to the 1 µg of nicotine that Domino et al. Predicted could be absorbed from such tobacco smoke is so low that it would not produce systemic levels of nicotine or coat and then detectable by any of the techniques currently used to assess such exposure.The main problem with the inference in these authors letter is a 500-fold error in the calculations used to determine the vegetable equivalent of toxicologically meaningful exposure to tobacco smoke.
Previous studies indicate that approximately 500 micrograms of injected or inhaled nicotine is needed to produce the plasma cotinine level of 5ng per ml typically observed in persons exposed to moderate levels of environmental tobacco smoke.2,3 One microgram of nicotine might produce a few picograms of cotinine per ml of plasma, which would not be detected by the assays commonly used to assess exposure to environmental tobacco smoke,3 or by the assay used by Domino et al.4
Determining the amount of vegetable consumption suggestive of exposure to cigarette smoke is also more complicated and physiologically difficult than implied by Domino et al. First it would take an approximately 500-fold increase in the amount of vegetables estimated by Domino et al. to produce exposure equivalent to half a cigarette a day- e.g., more than 100kg of tomatoes would have to be consumed in one day. Second, as acknowledged by Domino et al., nicotine exposure would be greatly reduced if vegetable skins, which contain most of the nicotine, were not eaten or if they were cooked in water, thereby extracting the nicotine. Third, ingesting nicotine is not equivalent to inhaling it, since absorption from the stomach is poor and 70 percent of the nicotine entering the circulation is metabolized during it's first pass through the liver. Finally, it has been well confirmed that the exposure to tobacco smoke indicated by a blood plasma concentration of 5 to 10 ng of cotinine per ml is of clear toxicologic importance,3 whereas there is no evidence that daily exposure to the equivalent of 1 percent of the smoke from one puff of a cigarette would be of toxicologic importance or could possibly confound assessment of environmental exposure.
Jack E. Henningfield, Ph.D.
National Institute on Drug Abuse
Doctor Domino replies:
To the Editor:
Eating vegetables does not make you an addict to nicotine. Since the publication of our letter, I have been overwhelmed by dozens of inquiries and commentaries from all over the world, ranging from the appropriate yo the curious and bizarre.
The purpose of our letter was to point out that small amounts of nicotine in some vegetables may be one possible explanation for the presence of nicotine and its metabolite cotinine in the body fluids, especially urine, of nonsmokers. The amount of nicotine in certain vegetables is obviously too small to produce any pharmacologic or toxicologic effects. The difference between a small amount of nicotine in certain vegetables and the large amount in one average tobacco cigarette offers of marvelous lesson, both pharmacologic and toxicologic on the importance of dose-effect relations. We never intended to suggest that vegetarians could become nicotine addicts, or that children who ate vegetables have a legitimate reason for refusing to eat them.
Doctor Henningfield apparently agrees with us that nicotine can be found in certain vegetables. Certainly 1 µg of nicotine is inhaled from tobacco smoke or eaten in certain vegetables will not cause any detectable physiologic changes, And it's a level in blood cannot be measured with most chemical assays including ours. Urinary cotinine levels are a far better measure of nicotine exposure then plasma levels. This statement that it takes 500 µg of injected or inhale nicotine To produce a coat ending level of 5ng per milliliter refers to plasma, not urine. Urinary cotinine levels would surely be measurable in persons eating less than 100 kg of tomatoes a day.
I agree that determining the amount of vegetable consumption that would be comparable to a reasonable level of passive exposure to cigarette smoke is very difficult. Someone should conduct the crucial experiment of recruiting a nonsmoking volunteers to eat reasonable amounts of vegetables containing nicotine and measuring their plasma and urinary levels of nicotine and cotinine. Only then will we know the contribution of eating such vegetables to the presence of cotinine, especially in the urine of nonsmokers not exposed to tobacco smoke. I stand behind our letter and say it loud and clear - let us do more research.
Edward F. Domino, M.D.
University of Michigan