Elsevier

Nutrition

Volume 19, Issue 1, January 2003, Pages 11-15
Nutrition

Applied nutritional investigation
Lower serum levels of β-carotene in Lithuanian men are accompanied by higher urinary excretion of the oxidative DNA adduct, 8-hydroxydeoxyguanosine: The LiVicordia study

https://doi.org/10.1016/S0899-9007(02)00837-7Get rights and content

Abstract

Objective

In 1995, middle-aged Lithuanian men had a four-fold higher risk than Swedish men of dying from coronary heart disease. The cross-sectional LiVicordia study had reported significantly lower levels of the lipid-soluble antioxidants lycopene, β-carotene, and γ-tocopherol among Lithuanian men than among Swedish men. We examined whether there were differences in urinary 8-hydroxydeoxyguanosine (8OHdG), a marker of oxidative stress, between these groups of men.

Methods

Using automated coupled column high-performance liquid chromatography with electrochemical detection, we examined 50-y-old men randomly sampled from Linköping, Sweden (n = 99) and Vilnius, Lithuania (n = 109) with regard to urinary concentrations of 8-OHdG.

Results

Levels of 8-OHdG were higher in the Lithuanian men than in the Swedish men (20.9 ± 0.91 versus 14.9 ± 0.75 nM/L, P < 0.001), and this difference was evident in smokers (P < 0.01) and non-smokers (P < 0.001). Serum levels of α- and β-carotene were inversely correlated to urinary 8-OHdG levels (P < 0.05 in both cases). Habitual smoking and low levels of β-carotene contributed significantly to higher oxidative DNA damage expressed as urinary 8-OHdG.

Conclusions

These findings indicate that increased urinary 8-OHdG levels accompany lower serum levels of antioxidants in Lithuanian men. They supported previous suggestions that increased oxidative stress may be one factor behind the higher mortality in Lithuanian men.

Introduction

A dramatic health divide in all-cause and coronary heart disease (CHD) mortality has developed during the past 20 y between Eastern and Western Europe.1, 2 As a result, in 1995 mortality from CHD among middle-aged men was four times higher in Lithuania than in Sweden.3 The causes for this difference are poorly understood. Previous epidemiologic studies4 and our own data3 have indicated that the traditional risk factors for CHD, i.e., high blood pressure, smoking, and lipid profiles, cannot explain the mortality differences between Eastern and Western European countries. Several reports have found that Eastern European populations have a lower intake of fresh fruit and vegetables, and explanations relating to nutrition and vitamin status1 and oxidative stress2 have been suggested. Lower serum levels of antioxidants have been found among Eastern European populations. In one part of the 1992 Czech MONICA study, plasma levels of the lipid-soluble antioxidants β-carotene and α-tocopherol were substantially lower than in a subsample of British civil servants examined in the same laboratory.5 In the Linköping– Vilnius coronary disease risk assessment study (LiVicordia), we compared 50-y-old men in Linköping, Sweden and Vilnius, Lithuania to obtain information on new possible causes for the increased CHD mortality rate in Lithuania. As previously reported, we found that the Lithuanian men had significantly lower serum levels of β-carotene, lycopene, and γ-tocopherol.3

The hypothesis that antioxidants might protect against chronic disease, especially CHD, is based on a large body of research. A consistent finding is that people who consume more fruit and vegetables have lower rates of CHD, stroke, and cancer.6 In a prospective study of elderly people, serum levels of carotenoids related inversely to all causes of mortality.7 In case-control studies of Czech men, plasma concentrations of β-carotene and α-tocopherol related to a lower risk for myocardial infarction.5 In a recent report, plasma levels of α- and β-carotene related negatively to a 5-y incidence of ultrasound-assessed atherosclerotic lesions (plaque) in carotid arteries.8 Likewise, in our study, plasma levels of β-carotene related negatively to ultrasound-assessed plaque in arteriae carotis and femoralis.9 However, the protective role of antioxidants in CHD and atherosclerosis has been shown in only epidemiologic studies, and supplementary studies have failed to show effects. Also, experimental models of atherosclerosis have been only partly confirmed by studies in men. Observed effects of nutrient intake and vitamin levels may be merely markers of a healthier lifestyle in general and not specifically related to oxidative stress. Arguments for the latter require monitoring of effects with the help of validated markers of oxidation.10

Reactive oxygen species are considered an important factor in various diseases, not only in CHD but also in cancer, arthritis, and asthma.11, 12, 13 Attacks on DNA by reactive oxygen species frequently result in oxidative DNA damage, e.g., hydroxylation of DNA.11, 12 The hydroxylation of deoxyguanosine is one such example, leading to the formation of 8-hydroxydeoxy guanosine (8-OHdG), which is transported through the blood and excreted in the urine.12, 14 Therefore, 8-OHdG in urine may be used as a biomarker of oxidative DNA damage in vivo, although it also may be derived from hydroxyl radical attacks on deoxyguanosine in the nucleotide pool and thus be a marker of oxidative stress in the body overall. In the present investigation, we measured 8-OHdG in the urine of the 50-y-old men participating in the LiVicordia study.

Section snippets

Subjects

The LiVicordia study is a cross-sectional study comparing population-based samples of approximately 100 50-y-old men from Vilnius and Linköping. It was conducted concomitantly in Vilnius and Linköping from October 1993 to June 1994. A list of men born between 1st July 1943 and 30th June 1944, randomly selected and randomly ordered, was obtained from the census register in both cities. Exclusion criteria were serious acute or chronic diseases that could influence the results of the

Results

The urinary levels of 8-OHdG in 50-y-old men from Vilnius and Linköping are shown in Table II. The 8-OHdG levels were significantly higher in the Lithuanian men than in the Swedish men (P < 0.001), and the difference was evident in smokers and non-smokers (P < 0.01). The clear difference between men from Vilnius and Linköping is illustrated in Fig. 1. Partial correlations, controlled for country, showed negative correlations between 8-OHdG and both α- and β-carotene (r = −0.16, P = 0.03 and r

Discussion

The present study investigated two groups representing populations with a dramatic difference in all-cause mortality and mortality from CHD and cancer. A previous publication3 found significantly lower serum levels of the lipid-soluble antioxidants lycopene, β-carotene, and γ-tocopherol in Lithuanian men than in Swedish men. The present study describes the parallel finding of significantly higher urinary levels of 8-OHdG in these Lithuanian men.

The relevance of our findings is supported by

Acknowledgements

The authors thank Vanda Pettersson for analyses of 8-OHdG and Elisabeth Wilhelm, BPhil, for help with statistical analyses.

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    This study was supported by grant 06962 from the Swedish Medical Research Council.

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