Household exposure to passive cigarette smoking and serum micronutrient concentrations

¹ From the Department of Epidemiology, The Johns Hopkins School of Hygiene and Public Health, Baltimore.

² AJA is a recipient of a Preventive Oncology Academic Award from the National Cancer Institute (CA73790). GWC is a recipient of a Research Career Award from the National Heart, Lung, and Blood Institute (HL21670).

³ Address reprint requests to AJ Alberg, Department of Epidemiology, Room E6132B, The Johns Hopkins School of Hygiene and Public Health, 615 N Wolfe Street, Baltimore, MD 21205. E-mail: aalberg{at}jhsph.edu.

See corresponding editorial on page 1421.

ABSTRACT  
Background: The associations observed between passive smoking and adverse health outcomes have generated controversy. In part, this could be because the diets of passive smokers, like those of active smokers, differ from those of persons who are not exposed to cigarette smoke, especially with regard to antioxidants.

Objective: Our objective was to assess the relation between household exposure to passive smoking and serum concentrations of retinol, tocopherols, and carotenoids.

Design: A cross-sectional study was conducted in Washington County, MD, to compare exposure to passive smoking at home, recorded in a private census of county residents in 1975, with micronutrient concentrations assayed in serum collected in 1974. This comparison was possible for 1590 control subjects in nested case-control studies conducted between 1986 and 1998.

Results: Among persons who were not current smokers, those who lived with smokers tended to have lower serum total carotenoid, -carotene, ß-carotene, and cryptoxanthin concentrations than did those who lived in households with no smokers. There was little evidence that exposure to passive smoking was associated with reduced serum concentrations of lutein and zeaxanthin, lycopene, retinol, -tocopherol, or -tocopherol.

Conclusions: Among nonsmokers, exposure to passive smoking tended to be associated with lower serum concentrations of the carotenoids most strongly associated with active smoking (total carotenoids, -carotene, ß-carotene, and cryptoxanthin). The associations were weaker for passive smoking than for active smoking. The consistency of the associations observed for active and passive smoking indicates that exposure to passive smoking may result in decreased circulating concentrations of selected micronutrients.

Key Words: Passive smoking • environmental tobacco smoke • cigarette smoking • -carotene • ß-carotene • cryptoxanthin • lycopene • lutein • zeaxanthin • retinol • -tocopherol • -tocopherol

INTRODUCTION  
Persons who smoke cigarettes are known to differ from persons who never smoked with respect to several lifestyle behaviors, including eating less healthful diets and drinking more alcohol (1–5). The same may hold true, to a lesser degree, for comparisons of nonsmokers exposed to passive smoking with nonsmokers who are not exposed to passive smoking. A specific reason for obtaining more information on this topic is to assist in the interpretation of studies of the health effects of passive smoking. Since the initial observation of an association between passive smoking and lung cancer in 1981 (6, 7), passive smoking has been studied widely to assess its potential harmful health effects. Passive smoking has been judged to be causally associated with lung cancer (8) and may be linked with ischemic heart disease (9). Studies of the health effects of passive smoking often compared disease risk among nonsmokers who lived with a smoker (usually their spouse) with the risk among nonsmokers who did not live with any smokers. This design has been criticized on the grounds that households in which smoking takes place may differ from households with no smokers with respect to factors that are associated with disease risk other than passive smoking (10–12).

In the most extreme case, this set of circumstances could theoretically lead to the appearance of passive smoking being associated with adverse health outcomes when, in fact, the association was due to dietary differences rather than to passive smoking. A small proportion of the studies conducted to assess the health effects of passive smoking accounted for diet; for example, 8 of 39 studies reviewed by Hackshaw et al (13) for lung cancer risk controlled for diet.

For these reasons, the relation between passive smoking and dietary factors is worth clarifying. Several studies, summarized in Table 1, addressed this question. A common finding was lower fruit, vegetable, and micronutrient intakes (15, 16, 18, 23) by persons exposed to passive smoking relative to those not exposed to passive smoking. The specific micronutrients associated with lower intake have included ß-carotene or carotene (14, 15, 19, 23), retinol (15, 16), vitamin C (15–17, 22), and -tocopherol (16). Only 2 studies in Table 1 looked at serum concentrations of micronutrients, a better indicator of actual cell exposures to nutrients than dietary intake histories. Tribble et al (22) found lower plasma ascorbic acid concentrations in passive smokers than in unexposed persons. However, in another study, persons exposed to passive smoking in the workplace had higher serum concentrations of ß-carotene and -tocopherol than did those not exposed to tobacco smoking in the workplace, but only 74 persons were observed (20). The present study was conducted to further address this question by assessing the relation between passive smoking and serum micronutrient concentrations in a larger study population (n = 1590) and for a broader range of micronutrients.

View this table:
TABLE 1. Summary of studies of the association between passive smoking and dietary factors¹  

SUBJECTS AND METHODS  
Two resources were used to conduct this cross-sectional study: 1) the Washington County, MD, serum bank (CLUE I) and 2) a private census conducted in Washington County. The serum bank study was the source of serum micronutrient information and smoking status (whether the individual smoked), and the census was the source of passive smoking data (whether the individual was exposed to environmental tobacco smoke in the household). The serum bank was established in the autumn of 1974 and the census was conducted shortly thereafter, in the summer of 1975. Because of the narrow time interval (7–10 mo) separating the blood draws from the census, these 2 data sources were considered to relate to a single time point for the purposes of this study.

Beginning in the 1980s, the serum bank has been used to conduct many nested case-control studies of micronutrients in relation to cancers. The pool of potential subjects for the present study comprised individuals who donated blood in 1974 and were subsequently selected as control subjects for these nested case-control studies (n = 2142); for the 53 persons whose serum had been assayed twice, data were limited to the initial assay. From this group, 1717 were linked to the private census, the source of passive smoking data, on the basis of name and birth date. Seven institutionalized individuals were excluded, as were 29 with a history of cancer. The study population was further limited to index subjects who were heads of households or spouses of heads of households because relatively few persons (n = 87) were other household members, and these do not share the same likelihood of exposure to passive smoking and shared meals as do spouses. The study population of index subjects was limited to heads of households or spouses of heads of households, but the source of the index subjects' exposure to passive smoking could be any household member. The predominant source of exposure to passive smoking at home was the spouse; 84% of persons exposed to passive smoking had a spouse who smoked. The micronutrient data were most complete for ß-carotene and lycopene; the 4 individuals with missing data for either of these were excluded, resulting in a final study population of 1590 individuals. The data collection protocols for the serum bank and the community-wide census are described briefly below.

The serum bank was established through a community-wide campaign to have as many adults as possible participate in a biomedical research program. Participation included donating a sample of blood and filling out a brief questionnaire. At the time of blood collection, a brief interview was administered to obtain information on demographic characteristics, smoking history, and use of selected medications during the 48 h before blood collection. The serum samples were stored at -70°C until assayed for micronutrient concentrations for the specific nested case-control studies done between 1986 and 1998.

For the private census conducted during the summer of 1975, a questionnaire was mailed to every residential address in Washington County. Interviewers went door to door to collect completed questionnaires or to help residents complete them. Tobacco use histories were collected for all household members aged 16.5 y. A total of 90225 persons, an estimated 90% of the population, were enumerated.

Laboratory assays
Serum micronutrients were not assayed at a single time point specifically for this study but were assayed for several nested case-control studies conducted over a 13-y period (1986–1998). During this period, assays were conducted in 4 different laboratories. Consequently, all results were adjusted for year of assay (to account for storage time) and laboratory (to account for differences between laboratories). Samples were protected from light and analyzed by HPLC for retinol, -tocopherol, -tocopherol, total carotene, -carotene, ß-carotene, cryptoxanthin, lutein and zeaxanthin, and lycopene (24, 25).

Statistical analyses
Assessment of tobacco exposure was limited to cigarette smoking data only for both active and passive smoking because of the small number of persons who smoked other forms of tobacco exclusively. Exposure to passive smoking refers to current exposure in 1975. The reports of active smoking in 1974 (serum bank study) and 1975 (census) agreed for 86.8% of the study population. Changes between former and current smoking status were noted for 8.1% of the study population; the remaining 5.1% had changes reported from former or current smoking to never smoking, which may be because of lack of reliability of responses or because different persons reported the information (self versus other household members). Most of these changes involved smokers who smoked a small number of cigarettes per day.

The PROC GLM procedure of SAS (version 6.12; Statistical Analysis Systems, Cary, NC) was used to estimate mean micronutrient concentrations according to active and passive smoking status, stratified by sex and adjusted for laboratory, year of assay, age, education, and marital status. The distributions of the micronutrients tended to be skewed toward high values so the data were log transformed. We thus present geometric means and results of tests of statistical significance that are based on the log-transformed data.

The principal variation in the measured micronutrient concentrations between laboratories was that the results for laboratory B were considerably lower than were those for the other laboratories. To address the concern that the values for this laboratory might have skewed the overall results, analyses excluding the assays performed in laboratory B were conducted; because the study results were not significantly altered by this, the results for the total study population are presented. We previously reported results on decreases in serum concentrations of certain micronutrients with storage time (26). The laboratory and duration of storage variables were highly correlated because of the use of certain laboratories during certain periods, so these variables were combined for adjustment purposes.

Passive smoking exposure was analyzed 3 ways: 1) as a dichotomous yes or no variable, 2) by dosage (summed number of packs of cigarettes per day of all smokers in the household other than the index subject), and 3) categorized according to the source of exposure (spouse or other).

RESULTS  
The characteristics of the study population (n = 1590) are summarized in Table 2. The average age was 54 y (range: 21–87 y). The study population had equal proportions of men and women and was almost exclusively white (99.1%).

View this table:
TABLE 2. Frequency distribution of selected characteristics of the study population by sex, Washington County, MD, 1974  
Serum concentrations of ß-carotene and lycopene were available for all 1590 individuals in the study population and for the percentage of subjects noted for the remaining micronutrients: retinol (80%), -tocopherol (72%), -tocopherol (52%), total carotenoids (72%), -carotene (72%), cryptoxanthin (66%), and lutein and zeaxanthin (62%). Serum concentrations of total carotenoids, ß-carotene, -carotene, and cryptoxanthin were significantly lower in current smokers than in never smokers for both men and women (Table 3). In men, significantly lower serum concentrations were also observed in former smokers than in never smokers for total carotenoids, ß-carotene, and cryptoxanthin.

View this table:
TABLE 3. Adjusted geometric mean serum micronutrient concentrations according to active smoking history, stratified by sex¹  
The adjusted mean serum micronutrient concentrations according to active and passive smoking status are summarized in Table 4. The most consistent pattern of associations to emerge from the many comparisons was the tendency of never and former smokers who were exposed to passive smoking to have lower serum concentrations of total carotenoids, ß-carotene, -carotene, and cryptoxanthin than did those not exposed to passive smoking at home. Among the never and former smokers, the differences that were significant for these carotenoid measures were limited to men for ß-carotene, to women for -carotene, to men who never smoked for total carotenoids, and to all never smokers plus men who formerly smoked for cryptoxanthin. Even when the differences were not significant, serum concentrations of total carotenoids, -carotene, ß-carotene, and cryptoxanthin were lower in persons exposed to passive smoking than in persons not exposed to passive smoking except for one stratum: serum -carotene concentrations in formerly smoking men.

View this table:
TABLE 4. Adjusted geometric mean serum micronutrient concentrations according to active and passive smoking status, stratified by sex¹  
For the remaining micronutrients, only 2 other significant differences were observed between persons exposed to passive smoking and those not exposed to passive smoking. Serum retinol concentrations were lower in men who currently smoked and who were exposed to passive smoking than they were in currently smoking men not exposed to passive smoking. Serum -tocopherol concentrations were higher in formerly smoking men exposed to passive smoking than in formerly smoking men not exposed to passive smoking (Table 4). There were no significant trends in serum micronutrient concentrations according to the number of cigarettes that household members smoked per day (data not shown).

The study population was composed of index subjects who were heads of households or spouses of heads of households, but the index subject could be exposed to passive smoking by a spouse or by other household members. Most of the exposure to passive smoking at home in this study was from spouses, but 16% of the study population was exposed only by household residents other than a spouse. Ancillary analyses were performed to assess the possible influence on the study results of exposure to passive smoking by a spouse compared with another household member. These analyses were performed for the 2 micronutrients (ß-carotene and lycopene) with complete data. These analyses indicated no important differences in the association between exposure to passive smoking and serum micronutrient concentrations according to whether the source of exposure was the spouse or another household member (data not shown).

DISCUSSION  
This study was conducted to assess whether exposure to passive smoking was associated with serum micronutrient concentrations. An initial characterization of the associations between active smoking and micronutrients showed that, for both men and women, serum concentrations of total carotenoids, -carotene, ß-carotene, and cryptoxanthin were significantly lower in current smokers than in never smokers. These findings are consistent with associations observed previously between active smoking and circulating concentrations of total carotenoids (27–29), ß-carotene (30–38), -carotene (30–32, 36, 37), and cryptoxanthin (31, 32, 36, 37). Retinol (27, 28, 34, 36, 39), the tocopherols (28, 32, 33, 36–38), lutein and zeaxanthin (34, 37), and lycopene (29, 30, 32, 34, 37) were not consistently observed to be associated with active smoking status in previous research, which is also in keeping with the findings of the present study.

With respect to the association between exposure to passive smoking and serum micronutrients, the primary finding of this study was that, in persons who were not current smokers, those who lived with smokers tended to have lower serum total carotenoid, -carotene, ß-carotene, and cryptoxanthin concentrations than did those who lived in households with no smokers. Interestingly, these carotenoid measures are the same ones that were observed to be inversely associated with active smoking both in the present study and in previous research. Nonsmokers who were exposed to passive smoking at home had serum concentrations of these carotenoids that were almost uniformly lower than in persons not exposed to passive smoking at home, but these differences were significant for only about one-half of the comparisons made. Of the significant differences, there was no consistent pattern observed between men and women or between index subjects who were former or never smokers.

The nutrients that were not associated with active smoking—-tocopherol, -tocopherol, lutein and zeaxanthin, and lycopene—also showed little evidence of being associated with exposure to passive smoking. In current smokers, serum retinol concentrations were significantly lower in those exposed to household passive smoking than in those not exposed, but the lack of association observed in never and former smokers casts doubt on the relevance of this observation. This exception aside, in active smokers, exposure to passive smoking was not associated with serum concentrations of any of the micronutrients studied.

The important associations observed in the present study were thus confined to individuals who were not current smokers and to the micronutrients most strongly associated with active smoking. Any additional contribution, beyond that of active smoking, that passive smoking may have on serum micronutrient concentrations may be difficult to detect in smokers because of the overwhelming influence of active smoking.

The specific pattern of associations observed (ie, passive household smoke exposure was associated with lower serum concentrations of total carotenoids, -carotene, ß-carotene, and cryptoxanthin) may reflect genuine associations given that these micronutrients are also associated with active smoking. However, the lack of dose-response trends raises the index of suspicion about this being a chance finding.

The results suggest a few possible hypotheses for future testing. Passive smoke exposure, as a source of oxidative stress (40, 41), could result in lowered circulating micronutrient concentrations by directly depleting antioxidant micronutrients (42, 43). The fact that passive smoking was associated primarily with lower circulating concentrations of the carotenoids that are associated with active smoking in the present study is compatible with the mechanism of action being an oxidative stress pathway.

Alternatively, because cigarette smokers have poorer diets than do nonsmokers (44), households with a smoker present may have poorer diets than do households with no smokers, resulting in less consumption of fruit and vegetables and hence lowered circulating micronutrient concentrations. Without information concerning dietary intake, we were unable to directly explore this hypothesis. However, the results of previous studies provide some support for this line of reasoning. In one study, wives' smoking habits were significantly associated with their husbands' ß-carotene consumption (45). In another study it was observed that, in nonsmoking men, those whose partner smoked had intakes of fruit, boiled vegetables, raw vegetables, and juice that were 9%, 4%, 11%, and 17% lower, respectively, than the intakes of those whose partner was not a smoker (21). These results lend credence to the notion that exposure to passive smoking in the home is associated with lower intake of carotenoids. However, it is not obvious why the associations would be limited to the carotenoids associated with active smoking and not observed uniformly for all the micronutrients studied. One possibility in this regard is that ß-carotene is the best biomarker of fruit and vegetable consumption (46); however, this argument does not seem tenable because, although the circulating concentrations of total carotenoids, -carotene, and cryptoxanthin were all strongly correlated with serum ß-carotene concentrations, so were lutein and lycopene concentrations.

A few additional considerations should be borne in mind when the findings of the present study are interpreted. Although we treated this as a cross-sectional study, it was not a cross-sectional study in the traditional sense. The assays of the stored samples were performed over a range of years and in different laboratories. We adjusted statistically for these factors in assessing the associations between passive smoking and serum micronutrients, but even statistical adjustment does not achieve the uniformity in outcome assessment that would have been accomplished if all the assays were performed during the same period by the same laboratory. It is reassuring that the established associations observed between micronutrient concentrations and active smoking were in the expected directions. The measure of passive smoking was specific to the household, but household exposure is the exposure source of primary interest when exploring the dietary link because of the potential importance of shared diets, as discussed above. The measurement of household smoking, as opposed to smoking only by the spouse, is a strength. Our finding that the associations between passive smoking and serum micronutrient concentrations were consistent whether the exposure was from the spouse or from other household members may be helpful in attempts to interpret the results of studies that rely solely on spouse smoking.

In summary, our primary finding was that nonsmokers exposed to passive smoking at home tended to have lower concentrations of some, but not all, carotenoids than did those with no smokers at home. The micronutrient measures that were lower in those exposed to passive smoking were total carotenoids, -carotene, ß-carotene, and cryptoxanthin—the same micronutrients that were lower in active smokers than in nonsmokers. As expected, the differences between those exposed and those not exposed tended to be smaller for passive smoking than for active smoking. The consistency of the associations observed for active and passive smoking, taken together, indicates that passive smoking is associated with lower circulating concentrations of selected carotenoids. If this result is replicated, studies with both serologic and dietary intake data will be required to unravel whether the association is due to a pathway that involves shared diets, to direct depletion of antioxidant nutrients, or to a combination of the 2 pathways.

REFERENCES  

1. Castro FG, Newcomb MD, McCreary C, Baezconde-Garbanati L. Cigarette smokers do more than just smoke cigarettes. Health Psychol 1989;8:107–29.
2. Hays R, Stacy AW, DiMatteo MR. Covariation among health-related behaviors. Addict Behav 1984;9:315–8.
3. Schoenborn CA, Boyd GM. Smoking and other tobacco use: United States, 1987. Vital and Health Statistics Series 10: data from the National Health Survey no. 169. Hyattsville, MD: US Department of Health and Human Services, 1989. (Publication no. PHS 89-1597.)
4. Osler M. Social class and health behavior in Danish adults: a longitudinal study. Public Health (Lond) 1993;107:251–60.
5. Kato I, Tominaga S, Suzuki T. Characteristics of past smokers. Int J Epidemiol 1989;18:345–54.
6. Hirayama T. Nonsmoking wives of heavy smokers have a higher risk of lung cancer: a study from Japan. Br Med J 1981;282:183–5.
7. Trichopoulos D, Kalandidi A, Sparros L, MacMahon B. Lung cancer and passive smoking. Int J Cancer 1981:27:1–4.
8. Respiratory and health effects of passive smoking: lung cancer and other disorders. Smoking and Tobacco Control Monograph Number 4. Bethesda, MD: National Cancer Institute, 1993. (NIH publication No. 93–3605.)
9. Law MR, Morris JK, Wald NJ. Environmental tobacco smoke exposure and ischaemic heart disease: an evaluation of the evidence. Br Med J 1997;315:973–80.
10. Roe FJC. Diet is important in assessing lung cancer risk factors in nonsmokers. Nutr Cancer 1994;22:203–6.
11. Nilsson R. Environmental tobacco smoke and lung cancer: a reappraisal. Ecotoxicol Environ Safety 1996;34:2–17.
12. Thornton A, Lee P, Fry J. Differences between smokers, ex-smokers, passive smokers, and non-smokers. J Clin Epidemiol 1994;47: 1143–62.
13. Hackshaw AK, Law MR, Wald NJ. The accumulated evidence on lung cancer and environmental tobacco smoke. Br Med J 1997;315:980–8.
14. Sidney S, Caan BJ, Friedman GD. Dietary intake of carotene in nonsmokers with and without passive smoking at home. Am J Epidemiol 1989;129:1305–9.
15. LeMarchand L, Wilkens LR, Hankin JH, Haley NJ. Dietary patterns of female nonsmokers with and without exposure to environmental tobacco smoke. Cancer Causes Control 1994;2:11–6.
16. Emmons KM, Thompson B, Feng Z, Hebert JR, Heimendinger J, Linnan L. Dietary intake and exposure to environmental tobacco smoke in a worksite population. Eur J Clin Nutr 1995;49:336–45.
17. Matanoski G, Kanchanaraksa S, Lantry D, Chang Y. Characteristics of nonsmoking women in NHANES I and NHANES I Epidemiologic Follow-up Study with exposure to spouses who smoke. Am J Epidemiol 1995;142:149–57.
18. Koo LC, Kabat GC, Rylander R, Tominaga S, Kato I, Ho J H-C. Dietary and lifestyle correlates of passive smoking in Hong Kong, Japan, Sweden, and the U.S.A. Soc Sci Med 1997;45:159–69.
19. Steenland K, Sieber K, Etzel RA, Pechacek T, Maurer K. Exposure to environmental tobacco smoke and risk factors for heart disease among never smokers in the Third National Health and Nutrition Examination Survey. Am J Epidemiol 1998;147:932–9.
20. Howard DJ, Ota RB, Briggs LA, Hampton M, Pritsos CA. Environmental tobacco smoke in the workplace induces oxidative stress in employees, including increased production of 8-hydroxy-2'-deoxyguanosine. Cancer Epidemiol Biomarkers Prev 1998;7:141–6.
21. Osler M. The food intake of smokers and nonsmokers: the role of partner's smoking behavior. Prev Med 1998;27:438–43.
22. Tribble DL, Giuliano LJ, Fortmann SP. Reduced plasma ascorbic acid concentrations in nonsmokers regularly exposed to environmental tobacco smoke. Am J Clin Nutr 1993;58:860–90.
23. Curtin F, Morabia A, Bernstein MS. Relation of environmental tobacco smoke to diet and health habits: variations according to the site of exposure. J Clin Epidemiol 1999;52:1055–62.
24. Katrangi N, Kaplan LA, Stein EA. Separation and quantitation of serum ß-carotene and other carotenoids by high performance liquid chromatography. J Lipid Res 1984;25:400–6.
25. Sowell AL, Huff DL, Yeager PR, Caudill SP, Gunter EW. Retinol, -tocopherol, lutien/zeaxanthin, ß-cryptoxanthin, lycopene, -carotene, trans-ß-carotene, and four retinyl esters in serum determined simultaneously by reversed-phase HPLC with multiwavelength detection. Clin Chem 1994;40:411–6.
26. Comstock GW, Alberg AJ, Helzlsouer KJ. Reported effects of long-term freezer storage on concentrations of retinol, beta-carotene, and alpha-tocopherol in serum or plasma summarized. Clin Chem 1993; 39:1075–8.
27. Bolton-Smith C, Casey CE, Gey KF, Smith WCS, Tunstall-Pedoe H. Antioxidant vitamin intakes assessed using a food-frequency questionnaire: correlation with biochemical status in smokers and non-smokers. Br J Nutr 1991;65:337–46.
28. Chow CK, Thacker RR, Changchit C, et al. Lower levels of vitamin C and carotenes in plasma of cigarette smokers. J Am Coll Nutr 1986;5:305–12.
29. Russell-Briefel R, Bates MW, Kuller LH. The relationship of plasma carotenoids to health and biochemical factors in middle-aged men. Am J Epidemiol 1985;122:741–9.
30. Aoki K, Ito Y, Sasaki R, Ohtani M, Hamajima N, Asano A. Smoking, alcohol drinking and serum carotenoid levels. Japan J Cancer Res 1987;78:1049–56.
31. Brady WE, Mares-Perlman JA, Bowen P, Stacewicz-Sapuntzakis M. Human serum carotenoid concentrations are related to physiologic and lifestyle factors. J Nutr 1996;126:129–37.
32. Buiatti E, Munoz N, Kato I, et al. Determinants of plasma antioxidant vitamin levels in a population at high risk for stomach cancer. Int J Cancer 1996;65:317–22.
33. Comstock GW, Menkes MS, Schober SE, Vuilleumier J-P, Helsing KJ. Serum levels of retinol, ß-carotene, and -tocopherol in older adults. Am J Epidemiol 1988;127:114–23.
34. Marangon K, Herbeth B, Lecomte E, et al. Diet, antioxidant status, and smoking habits in French men. Am J Clin Nutr 1998;67:231–9.
35. Margetts BM, Jackson AA. The determinants of plasma ß-carotene: interaction between smoking and other lifestyle factors. Eur J Clin Nutr 1996;50:236–8.
36. Pamuk ER, Byers T, Coates RJ, et al. Effect of smoking on serum nutrient concentrations in African-American women. Am J Clin Nutr 1994;59:891–5.
37. Ross MA, Crosley LK, Brown KM, et al. Plasma concentrations of carotenoids and antioxidant vitamins in Scottish males: influences of smoking. Eur J Clin Nutr 1995;49:861–5.
38. Stryker WS, Kaplan LA, Stein EA, Stampfer MJ, Sober A, Willett WC. The relation of diet, cigarette smoking, and alcohol consumption to plasma ß-carotene and -tocopherol levels. Am J Epidemiol 1988;127:283–96.
39. Jarvinen R, Knekt P, Seppanen R, Heinonen M, Aaran R-K. Dietary determinants of serum ß-carotene and retinol. Eur J Clin Nutr 1993; 47:31–41.
40. Duthie GG. Antioxidant status in smokers. In: Packer L, Fuchs J, eds. Vitamin E in health and disease. Marcell Dekker: New York, 1993.
41. Papas AM. Determinants of antioxidant status in humans. Lipids 1996: 31:S77–82.
42. Eiserich JP, van der Vliet A, Handelman GJ, Halliwell B, Cross CE. Dietary antioxidants and cigarette smoke-induced biomolecular damage: a complex interaction. Am J Clin Nutr 1995;62(suppl): 1490S–500S.
43. Handelman GJ, Packer L, Cross CE. Destruction of tocopherols, carotenoids, and retinol in human plasma by cigarette smoke. Am J Clin Nutr 1996;63:559–65.
44. Dallongeville J, Marceaux N, Fruchart JC, Amouyel P. Cigarette smoking is associated with unhealthy patterns of nutrient intake: a meta-analysis. J Nutr 1998;128:1450–7.
45. Shibata A, Paganini-Hill A, Ross RK, Yu MC, Henderson BE. Dietary beta-carotene, cigarette smoking, and lung cancer in men. Cancer Causes Control 1992;3:207–14.
46. Ziegler RG, Mayne ST, Swanson CA. Nutrition and lung cancer. Cancer Causes Control 1996;7:157–77.