Abstract

Plasma total homocysteine (tHcy) is a risk marker, and smoking is an established risk factor for cardiovascular disease. It is unclear if the effect of smoked tobacco on homocysteine is mediated by nicotine or other combustion products in smoked tobacco. Snus (moist smokeless tobacco) is high nicotine-containing tobacco, and little is known about the effect of snus on plasma homocysteine. Therefore, we studied, in a cross-section of subjects (n = 1375) from the Northern Sweden Health and Disease Study, with strictly defined current smokers (n = 194) and snus users (n = 47), the impact of tobacco exposure on tHcy, assessed by self-reported tobacco habits and plasma cotinine concentrations. The snus users had higher cotinine concentrations than the smokers. Cotinine, creatinine, methylmalonic acid, and the methylenetetrahydrofolate reductase genotype (MTHFR) T allele were positively associated with tHcy among the smokers, but not among the snus users. No association was observed between tHcy and the number of cigarettes/day. There was a positive association between cotinine and tHcy in the smokers, but not among the snus users. This indicates that substances other than nicotine in tobacco smoke could be responsible for the differential effects on homocysteine status. Self-reported smoking should be complemented by a cotinine assay whenever possible.

Highlights

  • Plasma total homocysteine is primarily considered to be a biomarker of functional vitamin B12 and folate status, and has been demonstrated to be useful as a general risk marker of cardiovascular disease (CVD) [1,2]. tHcy is associated with cardiovascular risk factors [3] and correlates with the Framingham cardiovascular risk score [4]

  • 74 nmol/L among the never tobacco users, and both the smokers and snus users had high concentrations, with the highest concentrations being observed in the latter group

  • We evaluated the effects of tobacco on tHcy by using both self-reported tobacco habits and plasma cotinine concentrations as a more objective measure of nicotine exposure

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Summary

Introduction

Plasma total homocysteine (tHcy) is primarily considered to be a biomarker of functional vitamin B12 and folate status, and has been demonstrated to be useful as a general risk marker of cardiovascular disease (CVD) [1,2]. tHcy is associated with cardiovascular risk factors [3] and correlates with the Framingham cardiovascular risk score [4]. Plasma total homocysteine (tHcy) is primarily considered to be a biomarker of functional vitamin B12 and folate status, and has been demonstrated to be useful as a general risk marker of cardiovascular disease (CVD) [1,2]. The nicotine content/g tobacco is lower in snus compared to cigarettes, but the bioavailability is higher, and the observed plasma cotinine concentrations are often reported to be similar or even higher in snus users than in smokers [8,9,10]. This study’s primary aim was to investigate if smoking is a stronger determinant for tHcy in plasma than the smokeless tobacco product snus after adjustment for potential confounders. We wanted to explore whether plasma cotinine concentrations were a better predictor of tHcy concentrations than self-reported smoking data

Study Population
Blood Sampling and Laboratory Procedures
Statistical Analysis
Results
Discussion
Strengths and Limitations
Conclusions
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