Why is cadmium in cigarettes

Forest fires and volcanoes also release some cadmium to the air. People are exposed to cadmium through their diet, since cadmium is absorbed into plant and animal foods that people eat. People are exposed to higher amounts of cadmium by breathing cigarette smoke. In the workplace, people are exposed where cadmium is used or generated, such as in battery manufacturing, metal soldering, or welding.

When eaten, large amounts of cadmium can severely irritate the stomach and cause vomiting and diarrhea. Exposure to low levels of cadmium in air, food, water, and particularly in tobacco smoke over time may build up cadmium in the kidneys and cause kidney disease and fragile bones. Cadmium is considered a cancer-causing agent. This study confirms that tobacco is a notable source of many heavy metal pollutants particularly Cd and Pb. The amount of Cd inhaled from smoking one pack of 20 cigarettes of different cigarette brands is estimated to be 1.

This value is comparable with the values from UK cigarettes 1. The small variation could be possibly attributed to Cd soil content, type of tobacco, growth conditions, and tobacco treatment process. The amount of Pb inhaled from smoking one pack of 20 cigarettes of the brands studied is estimated to be 1. The author would like to thank Dr. The author firmly declares that he has no direct financial relation with any commercial identity mentioned in this paper that might lead to a conflict of interests.

This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors.

Read the winning articles. Journal overview. Special Issues. Academic Editor: T. Received 03 Oct Accepted 14 Nov Published 12 Mar Introduction The consumption of tobacco products and number of smokers have been increasing steadily all over the world.

Table 1. Results obtained for the standard reference materials together with certified value. Table 2. Table 3. Galazyn-Sidorczuk, M. Erzen and L. View at: Google Scholar A. Al-Bader, A. Omu, and H. Rey, F. Turcotte, C. Lapointe, and E. View at: Google Scholar J. Shaham, A. Meltzer, R. Ashkenazi, and J. Paakko, S. Anttila, and P. View at: Google Scholar T. Fowles and E. We also checked for potential interactive effects on blood cadmium concentration between smoking status and intake of fruit and vegetables or antioxidative nutrients, adjusted for covariates [age 4 , 39 — 41 , geographical region 42 , and BMI 42 ].

All statistical analyses were performed with the SPSS statistical package version Age, height, weight, and BMI did not differ with smoking status Table 1. Family income, alcohol consumption, and employment status also did not differ due to smoking status. However, the level education differed between the groups, and the percentage of men with less than a high school education was higher for the smokers than for the nonsmokers.

As expected, blood cadmium concentrations were also higher in the smokers. The men included in the study did not differ from those excluded in demographic variables or food intake data not shown.

General characteristics and blood cadmium concentrations of the participants by smoking status 1. From chi-square tests for categorical variables and Student's t test for continuous variables.

The smokers consumed more meat and eggs than the nonsmokers, but daily nutrient intakes did not differ due to smoking status Table 2. The overall mean daily intakes of fruits and vegetables were Dietary nutrient and food group intakes of the men by smoking status 1. This trend was not observed among nonsmokers.

In the generalized linear model adjusted for age and BMI, higher fruit intake was associated with higher vitamin C and fiber intakes data not shown. Blood cadmium concentrations of the men by tertile of food group intake and smoking status 1. We tested the relationships between fruit, vegetable, and antioxidative nutrient intakes with blood cadmium concentration adjusted for age and BMI. Multiple regression analysis of fruit, vegetable, and antioxidant intakes and blood cadmium concentration of the men by smoking status 1.

Blood cadmium concentrations and food group and nutrient intakes were log-transformed and adjusted for age and BMI. The objectives of this study were to evaluate the effects of smoking status on blood cadmium concentrations in adult male participants and to determine any relationship between these factors and their dietary habits. We found that blood cadmium concentrations were significantly higher in heavy smokers than in moderate smokers and nonsmokers, consistent with previous studies that showed cigarette smoking leads to increased blood cadmium concentrations 6 — 9.

We found that the blood cadmium concentrations of the adult men in this study, including those of the nonsmokers, were higher than those reported in Sweden 39 , Italy 40 , China 41 , and Taiwan 43 , but were similar to those of other Korean 44 , 45 and Japanese 46 , 47 populations.

Blood cadmium concentrations are known to be influenced by factors other than cigarette smoking, such as diet. Previous studies have estimated that the dietary intake of cadmium in adult men in Korea is In the typical Korean diet, fruit is not considered to be an important food group contributing to cadmium intake Several studies have found that lifestyle patterns, including dietary habits, are generally less healthy among smokers than among nonsmokers Cigarette smokers reportedly consume less fruit and vegetables than nonsmokers 10 , 11 , 13 — Woo et al.

In our study, smoking status was not associated with fruit and vegetable consumption. However, lower fruit intake was associated with greater blood cadmium concentrations; the association was not a result of decreased consumption associated with smoking. Cadmium is a toxic metal that produces oxidative stress by disturbing the prooxidant-antioxidant balance Smokers' low intakes of fruit, which are rich in antioxidants, make them more susceptible to oxidative damage caused by free radicals.

Antioxidants such as vitamin C derived from fruit also modulate smoking-dependent cadmium toxicity through their antioxidative mechanisms. Studies have also shown that supplemental dietary vitamin C exerts both curative and preventative effects on cadmium toxicity Investigators have found that vitamin C can ameliorate the toxicities of heavy metals, including cadmium 22 — 24 , by binding inorganic elements and restricting their movement across biological membranes Inhibiting cadmium absorption may be another mechanism by which vitamin C and fiber decrease cadmium concentrations in the blood.

Experimental animal studies have shown that fiber inhibits the gastrointestinal absorption of cadmium, possibly due to the formation of insoluble complexes with phytates in the intestine 27 , High fiber consumption can also decrease cadmium absorption in humans Further high absorption of cadmium may partly be low body iron stores, as both cadmium and iron compete for uptake by DMT1 29 — Thus, vitamin C, especially with iron supplements, may indirectly decrease cadmium concentrations by improving iron absorption in the gastrointestinal tract Our study results showed that vitamin C and fiber were negatively related to blood cadmium concentrations, indicating that high intakes of vitamin C and fiber, which are abundant in fruit, may be beneficial to smokers.

This study had 3 main limitations. First, we did not consider whether a high cadmium content in the soil leads to high cadmium concentrations in certain fruits and vegetables. It has been previously reported that blood cadmium concentrations among nonsmokers are significantly higher in vegetarians than in nonvegetarians who consume a traditional mixed diet However, we do not think this would have influenced the results of the present study, because none of our participants were vegetarians, as indicated by the lowest daily meat intake in the FFQ being 8.

Moreover, with the negative association between fruit intake and cadmium concentrations, fruit was either not a source of exposure or, despite being a source of exposure, still provided a benefit. Second, we were not able to include data on nutrient intakes from dietary supplements, because although approximately one-tenth of the participants stated they used dietary supplements of some sort, they were unable to recall the names or types of supplements.

Third, the sample for this study was relatively small. Further studies incorporating nutrient intakes from supplements and with larger samples need to be conducted to explore the potential beneficial effects of vitamin C intake on smokers.

However, we think this is the first report that blood cadmium concentrations in cigarette smokers are inversely associated with the consumption of fruit. One notable feature of our study is that we estimated intakes of fruits and vegetables using a semiquantitative FFQ, which reflects long-term food consumption. In conclusion, we found that fruit consumption and vitamin C and fiber intakes may protect against elevated cadmium concentrations induced by smoking.

Future studies are warranted to explore mechanisms related to the antioxidative effects or absorption regulation that are responsible for these effects. Our work suggests that public health interventions for smokers should not only focus on smoking cessation but also on improving the diet, including promoting increased fruit consumption, as part of a comprehensive effort to reduce the risk of disease.

All the authors read and approved the final manuscript. Increased serum cadmium and strontium levels in young smokers: effects on arterial endothelial cell gene transcription. Arterioscler Thromb Vasc Biol. Google Scholar. Cadmium, lead, and thallium in mainstream tobacco smoke particulate. Food Chem Toxicol. Cekic O. Effect of cigarette smoking on copper, lead, and cadmium accumulation in human lens.

Br J Ophthalmol. Unusually high blood cadmium associated with cigarette smoking among three subgroups of the general population, Quebec, Canada. Sci Total Environ. Hazards of heavy metal contamination. Br Med Bull. In humans, reduced zinc concentrations are associated with adverse health outcomes including impaired immune system function and a possible role in carcinogenesis [ 10 , 18 , 19 ].

An inverse relationship has been reported for serum cadmium and zinc levels amongst cigarette smokers [ 20 ]. Few biomarkers have been validated as predictors of disease development [ 9 ]. This review examines cadmium and zinc levels in smokers and assesses associations between cadmium concentrations in blood, urine, and tissues with tobacco-related diseases.

Tobacco plants absorb metal ions and compounds from the soil through their roots, and by translocation from roots to leaves. Factors that influence the levels of metals absorbed by tobacco plants include native metal concentrations in soil, use of soil amendments such as phosphate fertilizers, animal waste, or sewage sludge, and soil pH [ 21 , 22 , 23 ]. Tobacco contains numerous bioavailable toxic metals, including arsenic, barium, beryllium, cadmium, chromium, cobalt, lead, manganese, nickel, and uranium [ 1 , 24 , 25 ].

Seventy three metals have been identified in tobacco smoke [ 2 , 26 ]. Metal transfer rates from tobacco to tobacco smoke are influenced by the volatility of the metal and cigarette design [ 2 , 27 , 28 ]. Though present at lower concentrations in tobacco than some other metals [ 24 ], cadmium readily transfers to mainstream smoke in concentrations higher than most other metals due to the volatility of the transported form [ 2 , 27 ]. Tobacco filler from over packs of cigarettes purchased in 20 areas around the world between and varied in cadmium concentration between 0.

More recently, cadmium concentrations in tobacco filler were analyzed and found to vary from 2. Cadmium concentrations in mainstream cigarette smoke generated under the International Organization for Standardization ISO smoking regimen [ 31 ] for 50 Philip Morris International varieties ranged from 1. Counterfeit U. Under an intense smoking machine regimen, mainstream smoke cadmium levels of legal U. Zinc levels in tobacco are not reported as frequently as cadmium, but one study reported a range spanning Though a significant portion of zinc is liberated from tobacco during combustion, zinc is less volatile than cadmium and does not pass beyond the filter into mainstream smoke as efficiently as cadmium [ 27 , 36 ].

Furthermore, the recommended daily intake for zinc is orders of magnitude higher than the levels of zinc in tobacco smoke [ 37 ]. The levels of zinc in tobacco smoke relative to physiological concentrations suggest that biological levels of zinc would be negligibly affected by the small amount transported in tobacco smoke. Smoking is a major non-occupational source of exposure to cadmium [ 11 ].

Smokers have higher concentrations of cadmium in urine, blood, hair, and tissues than nonsmokers whose principle source of exposure is the diet [ 38 , 39 , 40 , 41 , 42 ]. Multiple reports have shown correlations between urine cadmium concentration and smoking status, including correlations with number of pack years smoked and age-dependent accumulation [ 38 , 39 , 40 , 41 ].

The biological half-life of cadmium based on creatinine-adjusted urine cadmium concentrations is The 90th and 95th percentile urine cadmium concentrations for smokers age 50 and older in the CDC study were 1. It is important to note that the 95th percentile urine cadmium concentrations for U. Using — data from the same National Health and Nutrition Examination Survey NHANES , Richter and colleagues reported population level creatinine adjusted and unadjusted cadmium data for smokers and nonsmokers with or without exposure to secondhand smoke SHS [ 40 ].

Smokers, but not nonsmokers with SHS exposure, had higher adjusted and unadjusted geometric mean urine cadmium levels 0. Across several studies females have higher blood and urine cadmium levels than men [ 40 , 41 ]. Whereas urine cadmium concentrations correlate with chronic exposure; blood or serum cadmium concentrations provide information on recent cadmium exposures [ 11 , 39 , 41 ].

Reported blood cadmium concentrations and smoking status indicate correlations with recent smoking and number of cigarettes smoked per day [ 38 , 41 ]. Results from the German Environmental Survey II [ 38 ] showed that the blood cadmium grand mean concentration increased significantly with increasing cigarettes smoked per day, and blood cadmium concentrations were 3 to 6 times higher for current smokers at all percentiles than for never smokers at equivalent percentiles.

In the Adams and Newcomb study both blood and urine cadmium concentrations declined subsequent to smoking cessation with the decline in urine cadmium larger for men than for women [ 41 ]. Urine cadmium concentrations declined further in subsequent years, but did not reach levels comparable to never smokers.

Zinc, an essential nutrient, is physiologically important as an antagonist to oxidative challenge [ 18 , 46 ]. Sparse data exist on zinc concentrations in tobacco smoke [ 47 , 48 ].

During combustion, less zinc transfers from tobacco to smoke 0. Fresquez et al. Like cadmium [ 40 ], physiological levels of zinc may be influenced by sex and age [ 49 ]. Buxaderas et al. Galan et al. Other studies found that zinc concentrations in blood, serum, and tissues were lower in smokers than nonsmokers [ 19 , 51 , 52 ].

Other studies reported no association between zinc levels and smoking status [ 50 , 53 , 54 ]. Metals exposure is not tobacco use specific, but outside of uncontrolled occupational exposure [ 55 ], elevated cadmium concentrations in the lungs and other organs and bioaccumulation in the lungs are presented as biomarkers of exposure amongst smokers.

The temporal presence of metals in blood and urine makes these matrices easily accessible and informative for exposure biomonitoring [ 11 ]. Some metals that transfer from the tobacco filler to mainstream tobacco smoke, such as arsenic, cadmium, mercury, and lead, are naturally very toxic.

Other metals present in mainstream smoke are known to accumulate in tissues and reach potentially toxic concentrations following long term tobacco use [ 17 , 56 ]. Many of the metals found in tobacco smoke have been shown in various data to cause diseases of various organs and or cancers. These metals include aluminum, arsenic, cadmium, chromium, copper, lead, mercury, nickel and others [ 10 , 57 ]. However, smoking is not always shown to be a major source of exposure to these metals and it is not possible to attribute an adverse health outcome from tobacco use to any one metal.

Ultrafine tobacco smoke particles containing metals may pass through the pulmonary interstitial tissue intact or gradually dissolve, enter the circulation, and distribute to other organs before elimination from the body [ 7 , 8 , 39 , 41 , 54 , 58 , 59 , 60 ]. Cadmium accumulates in the kidneys [ 11 , 61 , 62 , 63 ] where levels can exceed cadmium levels in the lungs by 30 to 60 fold [ 62 , 63 ]. Although the lungs are the first organ impacted by inhalation exposure, the kidney is the principal organ targeted by chronic exposure to cadmium, whether ingested or inhaled [ 11 ].

Evidence for cadmium as a driver of increased risk of kidney disease is strong. A population level study of tobacco smoke exposure and urinary metals reported that older smokers in the United States have cadmium levels high enough to suggest elevated risk for cadmium-related toxicities such as renal tubular toxicity [ 40 ].

Recent evidence suggests that chronically elevated renal cadmium concentrations may interfere with iron homeostasis as well [ 64 ]. Increased cadmium concentrations induce expression of metallothionein. Zinc homeostasis also involves metallothionein binding and induced expression.

A proposed mechanism by which cigarette smoking disrupts zinc bioavailability is by nonselective metallothionein binding facilitated by adaptive cadmium induced metallothionein synthesis [ 10 , 65 , 66 ].

Conversely, because zinc and cadmium compete for the same binding targets, zinc administration can purportedly reduce the adverse effects of cadmium, possibly by zinc induction of metallothionein synthesis [ 67 , 68 ]. Navas-Acien et al.

Elevated plasma homocysteine levels are associated with peripheral artery disease. After adjusting for increased blood cadmium and lead associated with smoking, the odds ratio for homocysteine as a causative factor in peripheral artery disease decreased to less than 1. The authors suggested elevated blood cadmium and lead as possible causative agents for peripheral artery disease and possible causative or associative agents in the elevation of plasma homocysteine levels [ 71 ].

Current smokers in the study had urine cadmium concentrations greater than 0. Of note, the association between increased urine cadmium and myocardial infarction persisted in never smokers with an odds ratio of 1.

The odds ratio for myocardial infarction among never smokers with cadmium concentrations of 0. This strengthens the evidence that cadmium is a key contributor to elevated risk of myocardial infarction and further suggests that elevated cadmium levels are a possible etiologic contributor, regardless of the source.

A prospective cohort study of American Indian adults aged 45—74 years who had participated in the Strong Heart Study in — provided additional evidence that the known cardiovascular toxicity of cadmium might include contributions to cardiovascular disease. The group found that elevated urine cadmium concentration, considered as a biomarker of long-term cadmium exposure, was associated with increased incidence and mortality from cardiovascular disease [ 74 ].

The geometric mean cadmium level in the study population was 0. They concluded that cadmium exposure is a risk factor for cardiovascular disease with cardiovascular events, including deaths among study subjects [ 74 ]. In an early study of 47 male and female myocardial infarction patients Ponteva et al. Patients with myocardial infarction and control subjects had similar smoking habits percentages of nonsmokers, moderate smokers, and heavy smokers.

Ponteva et al. Re-evaluation using blood cadmium to blood zinc ratios may also provide stronger and more consistent data since some metals in blood are predominantly cell-associated [ 14 ]. In a study of smoking and nonsmoking hypertensive patients, higher cadmium concentrations in hair, blood, and urine samples were observed among the smoking hypertensive patients than among nonsmoking hypertensive patients [ 52 ].

Lower zinc concentrations were observed in hair and blood from the smoking hypertensive patients than from nonsmoking controls. While the data are not prospective in nature, the findings are relevant because the hypertensive patients who had higher hair, urine, and blood cadmium concentrations were smokers and because others have used cross-sectional data to report a concentration-dependent relationship between blood cadmium concentrations and the prevalence of hypertension [ 76 ].

However, in the study of smoking and hypertension, Afridi et al. This could be due to greater intra-individual variability in urine excretion rates than plasma concentrations or competition with cadmium for cellular metallothionein resulting in increased excretion of free zinc in the urine. Taken together, these two studies suggest elevated blood or urine cadmium concentrations as possible markers of risk for hypertension.

It would also be important to include lead exposure as a possible covariate in studies of cardiovascular disease risk including risk of hypertension [ 11 , 71 ]. In a large study of cardiovascular disease risk factors among postmenopausal women in the United States, Lee et al. Though they did not focus on association between smoking and cardiovascular health, they found no significant difference in relative cardiovascular disease risk between study participants whose diets were lower in zinc versus those whose diets had higher zinc levels when alcohol consumption was 9 g alcohol or less per day.

However, cardiovascular disease mortality risk was decreased for those in the higher dietary zinc levels when alcohol consumption was higher than 10 g per day.

Data from this study suggest a possible inverse correlation between dietary zinc status and risk of cardiovascular disease but alcohol consumption is an important covariate. In a study of adults in India, Singh et al. The lungs are one of the two principle target organs for toxicity effects resulting from inhalation exposure to cadmium [ 11 ].

Elemental cadmium is efficiently transferred to mainstream smoke from tobacco [ 2 , 28 , 33 ]. Consequently, it is expected that cadmium concentrations in cell-free bronchoalveolar lavage BAL fluid would be substantially higher for active smokers than nonsmokers without inhalation exposure to cadmium. Indeed, Sundblad et al. Mannino et al. No association of lung function and urine cadmium concentration in never smokers was found, suggesting that the correlation between urine cadmium concentration and FEV for smokers was a function of pulmonary exposure [ 81 ].

Lampe et al. Lin et al. They reported that obstructive lung disease was associated with low self-reported zinc intake regardless of smoking status. Although urine cadmium concentration was significantly correlated with pack years smoking, there was a stronger correlation between urine cadmium concentration and obstructive lung disorder than smoking status, which was apparently the principal source of the elevated cadmium concentrations.

Based on the ratio of zinc intake to cadmium excretion, they observed that higher zinc intake to urine cadmium concentration ratios were protective against obstructive lung disorder. The authors concluded that zinc has a moderating and protective effect in cadmium-related lung disease from tobacco use [ 83 ].

Hassan et al. There were significantly higher manganese and cadmium concentrations in lung tissue from smokers with more advanced stages of disease GOLD 4 than for smokers who were subclinically symptomatic or asymptomatic GOLD 0. Zinc concentrations decrease or do not significantly change due to smoking status while evidence exists that elevated pulmonary cadmium concentrations attributed to smoking are reflected in elevated blood cadmium concentrationsb [ 41 , 54 ].

For example, Morgan reported significantly elevated mean serum cadmium concentrations and suppressed mean serum zinc concentrations as distinct characteristics of patients with bronchogenic carcinoma, a leading cause of death in the U. Though bronchogenic carcinoma is considered to be predominantly a smoking-related disease, there was no information on smoking status in this early study [ 84 ].

Similarly, Davies et al. Voyatzoglou et al. They further reported that patients with bronchogenic carcinoma had elevated urinary zinc excretion compared to control subjects [ 87 ], as was reported by Afridi et al.

Andrews noted that mean levels of plasma zinc decreased with longer tumor duration from The findings of Strain et al [ 89 ] contrasted with those of Morgan, Davies, and Voyatzoglou [ 84 , 85 , 86 , 87 ]. Though the Strain et al. Strain and colleagues, however, did discuss the association between high cadmium concentrations and many types of cancer.

They proposed closer study of elemental ratios e. It has been suggested that zinc deficiency and increased tobacco-related cadmium exposures could result in increased incidences of COPD in developing countries [ 91 , 92 ]. Data from Lin et al. At the biochemical level, data supports an antagonistic role for pulmonary cadmium exposure and zinc homeostasis.

Xu et al. Both changes facilitate angiogenesis and cell migratory properties and are likely indicative of cell transformation to an early stage of cancer. Anetor et al. It has been proposed that zinc deficiency together with increased cadmium exposures from increased tobacco use in developing countries could result in increased incidences of prostate cancer [ 20 , 92 ].

In a summary of data from other published studies [ 93 , 94 , 95 , 96 , 97 , 98 , 99 , , ], Costello et al. Habib et al.