Correspondence
More on the Nicotine Content of Vegetables
N Engl J Med 1993; 329:1581-1582November 18, 1993
- Article
To the Editor:
Domino et al. (Aug. 5 issue)1 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 cotinine detectable by any of the techniques currently used to assess such exposure. The main problem with the inferences 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 μg of injected or inhaled nicotine is needed to produce the plasma cotinine level of 5 ng per milliliter typically observed in persons exposed to moderate levels of environmental tobacco smoke2,3. One μg of nicotine might produce a few picograms of cotinine per milliliter 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 al4.
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 100 kg 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 its first pass through the liver. Finally, it has been well confirmed that the exposure to tobacco smoke indicated by a plasma concentration of 5 to 10 ng of cotinine per milliliter 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.
4 ReferencesJack E. Henningfield, Ph.D.
National Institute on Drug Abuse, Baltimore, MD 212241
Domino EF ,Hornbach E ,Demana T . The nicotine content of common vegetables. N Engl J Med 1993;329:437-437
Full Text | Web of Science | Medline2
Jarvis MJ . Application of biochemical intake markers to passive smoking measurement and risk estimation. Mutat Res 1989;222:101-110
CrossRef | Web of Science | Medline3
The health consequences of involuntary smoking: a report of the Surgeon General. Rockville, Md.: Department of Health and Human Services, 1986.
4
Domino EF ,Hariharan M ,VanNoord T ,Demana T . Current experience with HPLC and GC-MS analyses of nicotine and cotinine. Med Sci Res 1992;20:859-860
Author/Editor Response
Dr. 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 to 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 the small amount of nicotine in certain vegetables and the large amount in one average tobacco cigarette offers a 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 hate vegetables have a legitimate reason for refusing to eat them.
Dr. Henningfield apparently agrees with us that nicotine can be found in certain vegetables. Certainly, 1 μg of nicotine inhaled from tobacco smoke or eaten in certain vegetables will not cause any detectable physiologic changes, and its level in blood cannot be measured with most chemical assays, including ours. Urinary cotinine levels are a far better measure of nicotine exposure than plasma levels. The statement that it takes 500 μg of injected or inhaled nicotine to produce a cotinine level of 5 ng 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 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 loud and clear -- let us do more research.
Edward F. Domino, M.D.
University of Michigan, Ann Arbor, MI 48109-0626- Citing Articles (7)
Citing Articles
1
James N. Hyde, Doug Brugge, James Repace, William Rand. (2004) Assessment of Sources of Second-Hand Smoke Exposure in a Putatively Unexposed Population. Archives of Environmental Health: An International Journal 59:11, 553-557
CrossRef2
Orazio Taglialatela-Scafati, Giovanni Appendino. 2003. Drug-like compounds from food plants and spices. , 43-74.
CrossRef3
Åse Marie Hansen, Anne Helene Garde, Jytte Molin Christensen, Nanna Eller, Lisbeth Ehlert Knudsen, Regine Heinrich-Ramm. (2001) Reference interval and subject variation in excretion of urinary metabolites of nicotine from non-smoking healthy subjects in Denmark. Clinica Chimica Acta 304:1-2, 125-132
CrossRef4
H. Thomas Karnes, John R. James, Clark March, Donald E. Leyden, Kent Koller. (2001) Assessment of nicotine uptake from cigarette smoke: comparison of a colorimetric test strip (NicCheck I™) and gas chromatography/mass selective detector. Biomarkers 6:6, 388-399
CrossRef5
B FURBEE, M WERMUTH. (1997) LIFE-THREATENING PLANT POISONING. Critical Care Clinics 13:4, 849-888
CrossRef6
Edward F. Domino. (1995) Nontobacco sources of cotinine in the urine of nonsmokers. Clinical Pharmacology & Therapeutics 57:4, 479-479
CrossRef7
James L. Repace, Alfred H. Lowrey. (1995) A Rebuttal to Tobacco Industry Criticism of "An Enforceable Indoor Air Quality Standard for Environmental Tobacco Smoke". Risk Analysis 15:1, 7-13
CrossRef
