Elsevier

Toxicology

Volume 180, Issue 2, 15 November 2002, Pages 121-137
Toxicology

The influence of cigarette smoking on circulating concentrations of antioxidant micronutrients

https://doi.org/10.1016/S0300-483X(02)00386-4Get rights and content

Abstract

Cigarette smoke is a significant source of oxidative stress, one potential mechanism for its untoward health effects. The antioxidant defense system is partly comprised of antioxidant micronutrients, making it important to understand the relationship between cigarette smoking and circulating concentrations of antioxidant micronutrients. A synthesis of the literature shows that compared with nonsmokers, on average, active smokers have greater than 25% lower circulating concentrations of ascorbic acid, α-carotene, β-carotene, and cryptoxanthin. The differences in blood concentrations of these micronutrients in former smokers is intermediate between never and current smokers, but average circulating concentrations of α-carotene, β-carotene, and cryptoxanthin were 16–22% lower in former smokers compared with never smokers. Differences in dietary habits between smokers and nonsmokers could potentially account for these associations. Dietary micronutrient intake is associated with blood micronutrient concentrations. Furthermore, patterns of micronutrient consumption by smoking status mimic the pattern of associations observed for blood concentrations. For example, when pooled across studies intake of vitamin C was 16% lower in current smokers and 2% lower in former smokers than in never smokers; the corresponding figures for β-carotene were 17 and 4%, respectively. Despite the strong potential for confounding, the differences observed between current smokers and nonsmokers seem to be due to an acute effect of smoking based on results of studies of smoking and antioxidant micronutrient concentrations that have either adjusted for dietary antioxidant micronutrient intake and other potential confounding factors or documented short term changes in circulating antioxidant micronutrient concentrations in smokers before and after smoking cigarettes. The associations observed with active smoking also appear to hold true for passive smoking, implying that even low-dose exposures to tobacco smoke can result in lowered circulating antioxidant micronutrient concentrations. Smoking was more weakly associated with circulating concentrations of vitamin E and the nonprovitamin A carotenoids lutein/zeaxanthin and lycopene. The combined evidence supports the conclusion that cigarette smoking is independently associated with lowered circulating concentrations of ascorbic acid and provitamin A carotenoids. These associations have implications for the design and interpretation of epidemiologic studies of antioxidant micronutrients in relation to health and disease. To the extent that these micronutrients are associated with health and longevity, this evidence documents yet another deleterious consequence of cigarette smoking on human health.

Introduction

The net result of regular inhalation of the smorgasbord of over 4700 chemicals found in cigarette smoke (Repine et al., 1997) is to cause increased risk of numerous illnesses, including the major killers of the developed world: coronary heart disease, cancer, and chronic obstructive pulmonary disease (US Surgeon General, 2001). One pathway that may contribute to the untoward health effects of cigarette smoking is smokers’ significant exposure to oxidative stress (Cross and Traber, 1997). Cigarette smoke contains free radicals and other oxidants in abundance. In one puff of a cigarette, the gas phase of smoke exposes the smoker to greater than 1015 free radicals and layered onto this exposure are the additional radicals and oxidants in the tar phase (Pryor and Stone, 1993). These direct exposures from cigarette smoke represent only a portion of the total oxidative stress eventually experienced by the smoker, as cigarette smoke also contributes to additional endogenous oxidant formation through effects on the inflammatory-immune response (Cross et al., 1998, MacNee, 2000).

Antioxidant micronutrients represent one line of host defense against oxidative stress (Evans and Halliwell, 2001), such as that stemming from cigarette smoke. Antioxidant micronutrients consumed in the diet may thus act to mitigate against some of the adverse effects of cigarette smoking. To understand if this is true, it is essential to achieve a clear understanding of the complex relationships between smoking and circulating concentrations of antioxidant micronutrients.

In this report, selected elements of the relevant epidemiologic evidence are systematically reviewed to assess the influence of cigarette smoking on circulating concentrations of individual antioxidant micronutrients. The focus is placed on antioxidant micronutrients that have received the greatest attention in this regard, namely vitamin C, E, and carotenoids. Summarized data showing overall study findings are used to emphasize major patterns. Percentage differences were estimated to circumvent the problem of study results being reported in different units. Summary percentage differences were calculated by pooling the weighted average percentage differences using the sample size as the weight for each study. Studies were included in the summary tables if they had 100 or more participants. If results of a study were not presented by smoking status for the total study population, the subgroups presented (usually gender) were collapsed using weighted averages to estimate the association in the total study population. Heterogeneity in the associations that may be present between subgroups is of interest, but is not addressed in the present report.

Section snippets

Active cigarette smoking and circulating micronutrient concentrations

The evidence consistently shows that compared with nonsmokers, current smokers have lower circulating concentrations of vitamin C (Table 1). On average, vitamin C concentrations were 27% lower in current smokers compared with nonsmokers and 6% lower in former smokers compared with never smokers (Table 1). Strong trends showed lower circulating vitamin C concentrations as the number of cigarettes smoked per day increased (Table 1), and significant negative correlations were observed when the

Passive smoking and circulating antioxidant micronutrient concentrations

The same pattern of associations observed between active smoking and circulating micronutrient concentrations also seems to extend to passive smoking. Compared with nonsmokers not exposed to environmental tobacco smoke (ETS), on average nonsmokers exposed to ETS have been observed to have circulating concentrations 15% or more lower of vitamin C (Farchi et al., 2001, Jendryczko et al., 1993, Tribble et al., 1993, Strauss, 2001), α-carotene (Alberg et al., 2000, Farchi et al., 2001), β-carotene (

Potential for confounding by diet

Based on the evidence reviewed thus far, strong inferences concerning the influence of smoking on circulating antioxidant micronutrient concentrations could be made if the only relevant characteristic that distinguished smokers from nonsmokers was smoking status. Such an idyllic situation is far from the truth, as persons who smoke cigarettes are known to differ from persons who never smoked with respect to several lifestyle behaviors, including eating less healthful diets. Furthermore, how the

Time since quitting in former smokers

The time period since quitting smoking may be a key factor to account for when evaluating both circulating concentrations and dietary intake of antioxidant micronutrients. In order to interpret data estimating the association between smoking and circulating antioxidant micronutrient concentrations by time since quitting smoking, it is important to consider the possibility that smokers who quit alter their dietary patterns upon quitting smoking and continue to do so with time since quitting.

Does confounding explain the association between smoking and circulating micronutrient concentrations?

The close interrelationship between smoking and dietary micronutrient intake make additional lines of evidence particularly critical to understanding the question of whether cigarette smoking directly results in reduced circulating concentrations of antioxidant micronutrients. Evidence concerning the acute effect of smoking on antioxidant micronutrient concentrations is provided by a study with measurements of circulating micronutrient concentrations taken shortly before and after a smoker

Summary and conclusions

When viewed in total, the data on the relationship between cigarette smoking and the selected antioxidant micronutrients considered here provide strong evidence that cigarette smoking is directly responsible for lower circulating concentrations of selected antioxidant micronutrients. The micronutrients most strongly influenced by smoking status are vitamin C and provitamin A carotenoids. The association with smoking for these micronutrients is substantial and the data support the presence of a

Acknowledgements

Dr Alberg is a recipient of a Preventive Oncology Academic Award from the National Cancer Institute (CA73790). Preparation of this manuscript was supported in part by grants from the National Institute of Aging (AG618033) and National Institute of Environmental Health Sciences (ES03819). The author thanks Ritu Sharma for valuable assistance in preparing this manuscript.

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