Monitoring micronutrients in cigarette smokers

Abstract

Smoking is associated with oxidative stress and increased risks of many chronic diseases that both shorten life and impair its quality. Low concentrations of several micronutrients, especially the antioxidants vitamin C and β-carotene, are also associated with smoking, and there has been much interest in determining whether deficiencies in micronutrients are involved etiologically in smoking-related diseases. The objective of this review was to bring together reports on dietary intakes, biochemical indicators of micronutrient status, and results of some intervention studies on micronutrients where authors had compared outcomes in smokers and non-smokers. The micronutrients discussed are vitamins A, E, and C; the carotenoids; some of the B-vitamin group; and the minerals selenium, zinc, copper, and iron. The data were then examined to determine whether effects on the biochemical markers of micronutrient status were due to differences in dietary intakes between smokers and non-smokers or to the consequences of inflammatory changes caused by the oxidative stress of smoking. It was concluded that although smoking is associated with reduced dietary intake of vitamin C and carotenoid-containing foods, inflammatory changes increase turnover of these micronutrients so that blood concentrations are still lower in smokers than non-smokers even when there is control for dietary differences. In the case of vitamin E, there is some evidence for increased turnover of this nutrient in smokers, but this has little to no influence on blood concentrations, and there are no differences in dietary intake of vitamin E between smokers and non-smokers. Serum concentrations of vitamin A, folate, and vitamin B₁₂ and B₆ markers do not appear to be influenced by smoking, although there is some influence of dietary intake on concentrations of these nutrients in the body. In the case of the minerals examined, the main effects on biochemical markers of mineral status were attributed to inflammation and were therefore greater in heavy or long-term smokers. Serum concentrations of selenium and erythrocyte GPx activity were lower in smokers. Erythrocyte CuZn–SOD activity and serum ceruloplasmin concentrations were elevated, while serum zinc concentrations were depressed only in heavy smokers. Lastly, smoking appears to affect iron homeostasis mainly by changing hemoglobin concentrations, which were in general increased. Serum iron, TfR, and ferritin were mostly unaffected by smoking, except in pregnancy where there is evidence of increased erythropoiesis causing lower saturation of plasma transferrin and some evidence of lowering of iron stores.

Introduction

The World Health Organization (WHO) ranks tobacco smoking among the 10 greatest risks to health [1] and estimates that 1 billion men and 250 million women currently smoke cigarettes. At present, approximately 5 million people die each year from tobacco-related illnesses, and if current trends continue, this figure will rise to about 10 million by 2025, most of the increase being in the Third World, where the annual number of deaths from smoking is predicted to rise to 7 million [2].

Smoking is a major risk factor for cancer, heart and lung disease [3], [4], and for every one person who dies of a smoking-attributable disease, 20 more are suffering with a least one serious smoking-related illness [3]. Smokers aged 45–64 years have a mortality rate three times that of non-smokers, while among smokers 65–84 years, there is a doubling of the mortality rate [5].

Cigarette smoke is a mixture of over 4000 chemicals containing many bioactive substances that undergo complex interactions with human biological systems [6]. One pathway that may contribute to the unwanted health effects of cigarette smoking is exposure to oxidative stress [7]. One “puff” of a cigarette exposes the smoker to more than 10¹⁵ free radicals and other oxidants, and additional free radicals and oxidants are found in the tar of a cigarette [8]. Further damage may be caused by the endogenous formation of oxidants, which affect the inflammatory-immune system [9]. The abundance of free radicals in cigarette smoke may induce oxidative stress in the respiratory and circulatory systems, and the lower concentrations of antioxidants found in smokers may be due to a sustained smoke-related oxidant load that depletes the antioxidants [10]. On the other hand, because antioxidants are potentially pro-oxidants, lower concentrations of antioxidants in smokers than non-smokers may be a defensive adaptation to the pro-inflammatory environment in smokers' tissues which may be associated with elevated acute phase proteins [11].

Several dietary micronutrients are important antioxidants; they play an important part in protecting against endogenous oxidant stress and may also protect against the oxidative stress caused by smoking. Many studies of cigarette smokers, however, have found they have lower intakes and lower blood concentrations of certain antioxidants and other micronutrients, e.g., vitamin C, β-carotene, and folate [12], [13], [14], [15]. There is a complex relationship between smoking and the circulating concentrations of micronutrients, and studies have shown conflicting evidence for the antioxidant capacity of important micronutrients, e.g., β-carotene [16]. In addition, the major antioxidants of interest may have different ways of protecting the body against oxidant-induced damage caused by smoking:

• Vitamin C is a water-soluble antioxidant that scavenges free radicals in the aqueous part of the cell, e.g., the cytoplasm.

• Vitamin E is the major scavenger of free radicals in the lipid phase, e.g., cell membranes.

• The antioxidant function of β-carotene depends on the oxygen tension in the microenvironment of the cell.

• Carotenoids are efficient quenchers of singlet oxygen and can directly scavenge free radicals and inhibit lipid peroxidation.

• Selenium is a cofactor for glutathione peroxidase (GSHPx), an important antioxidant enzyme for removing lipid hydroperoxides and hydrogen peroxide.

• Zinc, copper, and iron also have important roles in the body's enzymatic antioxidant defence systems.

• Folate, vitamins B₆ and B₁₂ are involved in the regulation of homocysteine and elevation of homocysteine is identified as an independent risk factor for cardiovascular disease (CVD).

This review will look at the concentrations of the following micronutrients: β-carotene and other carotenoids; vitamins A, B₆, B₁₂, C, E, and folate; and the minerals iron, zinc, copper, and selenium in the blood and diet of smokers and non-smokers and will discuss the influence of the acute phase response in interpreting the changes in plasma micronutrients (Fig. 1). In addition, the review will examine the various biomarkers linked to the functions of the nutrients listed.