1 Department of Medical Genetics, 2 Department of Clinical Chemistry, 3 Center of Preventive Medicine and 4 Research Center, Ullevål University Hospital, 0407 Oslo, Norway
* Author to whom correspondence should be addressed at: Department of Medical Genetics, Ullevål University Hospital, 0407 Oslo, Norway. Tel.: +47 22119860; Fax: +47 22119899; E-mail: l.j.retterstol{at}ioks.uio.no
(Received 13 September 2004; first review notified 1 October 2004; in revised form 2 November 2004; accepted 25 November 2004)
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ABSTRACT |
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INTRODUCTION |
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A recent meta-analysis pointed out that an alcohol intake of 20 g/day is associated with the lowest risk of developing coronary heart disease (Corrao et al., 2004). We wanted to investigate whether consumption of alcohol at this level reduced the levels of markers of inflammation. Since there are indications that wine (Grønbæk et al., 1995
; Renaud et al., 1999
), and perhaps red wine in particular (Goldberg et al., 2001
), confers special cardioprotective effects, we chose red wine as the source of alcohol in this study. We performed a crossover study to observe the effects of moderate intake of alcohol on CRP and fibrinogen levels.
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SUBJECTS AND METHODS |
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No restrictions were placed on how and when the participants should drink their wine. The study was approved by the regional ethics committee and all the participants gave their written, informed consent.
Measurements of CRP levels were analysed in the same run after the study was completed, using a high-sensitivity method (range 0.120 mg/l, intra-assay coefficient of variation <2% at 0.5 mg/l; Roche Diagnostics, Mannheim, Germany). Fibrinogen was consecutively measured using Clauss' method on fresh samples (Clauss, 1957). The procedure was executed blindly. The levels of lipids and liver enzymes were measured from freshly drawn blood using routine methods.
Since the distribution of CRP and fibrinogen levels is highly skewed, non-parametric methods were applied to test for differences and correlations (MannWhitney U-test, Spearman's correlation coefficient and KruskalWallis test). Multivariate linear regression analyses were performed to identify variables that were independently associated with CRP and fibrinogen levels, after ln-transformation of the variables with skewed distribution. We calculated that 90 individuals would be sufficient to obtain 80% test power to detect a difference of at least 10% of the levels of CRP and fibrinogen in this study.
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RESULTS |
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DISCUSSION |
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First, the amounts of alcohol were at least twice as high in the two previous studies. Observational studies suggest that intakes of 2040 g (Imhof et al., 2001) or one unit (Albert et al., 2003
) of alcohol every day were associated with the lowest levels of inflammatory markers. Furthermore, a meta-analysis has shown that an alcohol consumption of 20 g/day was associated with the lowest risk of developing coronary heart disease (Corrao et al., 2004
). The amount of alcohol consumed in the present study was lower (15 g), but still close to these levels. Therefore, one might expect that a glass of red wine a day would reduce both CRP and fibrinogen levels, but this was not the case in this study. Perhaps there is a threshold effect of alcohol on the levels of inflammatory markers above the amount consumed in this study. If the red wine intake had been two or three glasses, we might have observed a greater effect on the levels of inflammatory markers. In addition, the effects may differ when alcohol is consumed along with food, as in the two previous studies (Sierksma et al., 2002
; Estruch et al., 2004
). The participants in the latter study generally reported a higher daily intake of alcohol than in the present study and also included current smokers. Furthermore, different habits of alimentation between different countries such as Spain and Norway may influence the effects of wine.
Second, the baseline levels of CRP and fibrinogen were higher in both these trials compared with our study. The effect of alcohol may be less significant for lower than for higher levels of CRP and fibrinogen.
Third, small studies could differ by chance. Although this was not a large study, the sample size in this trial was two (Estruch et al., 2004) or three times (Sierksma et al., 2002
) larger than in the previous trials.
Finally, two-thirds of the participants in this trial were women, whereas the study by Estruch et al. (2004) included only men. However, we did not observe a significant reduction in CRP values after the wine period for men; on the contrary, the opposite trend was observed, although it was not statistically significant.
Fibrinogen levels were slightly reduced during the wine period in this study. One could speculate that red wine acts more on the fibrinolytic system and thereby decreases coagulation, which could reduce cardiovascular risk. However, we believe that a difference in the variance between the CRP and fibrinogen measurements is a more plausible explanation of why fibrinogen and not CRP levels showed a statistically significant result.
The observed reduction in total cholesterol levels, but not HDL, in the red wine period was surprising. One could speculate that red wine affects diet by lowering the intake of saturated fatty acids and thereby lowering total cholesterol. However, as indicated in Table 5, there was also a slight reduction in total cholesterol levels between inclusion and the abstention period, which may suggest that the subjects were on a slightly healthier diet while the study was being conducted, perhaps due to increased attention to their diet in general. We have no data to explore these speculations further.
The highly significant correlation between the two acute-phase reactants CRP and fibrinogen is not surprising, and is in line with our previous reports (Retterstol et al., 2002, 2003
). Similarly, CRP levels have been shown to correlate with BMI and HDL levels in previous studies (Retterstol et al., 2003
). The correlations to non-fasting triglycerides and glucose need to be confirmed in future studies, while a small effect on GGT was also observed in the study by Sierksma et al. (2002)
.
From samples obtained at inclusion, one might get the impression that wine-drinkers have lower CRP levels, while beer-drinkers have lower fibrinogen levels. These findings should be interpreted with caution, as these data were obtained from questionnaires and combinations of different alcoholic beverages were frequently reported. Randomized prospective studies comparing wine and beer (or other types of alcohol) should be used to address this question. In addition, data related to smoking and use of medication or other substances were also obtained from the same questionnaires. Theoretically, some participants may have given incorrect information. However, we tried to correct for any uncertainties when the physician interviewed the participants at inclusion.
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CONCLUSIONS |
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ACKNOWLEDGEMENTS |
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