Complementary effects of Mediterranean diet and moderate red wine intake on haemostatic cardiovascular risk factors

European Journal of Clinical Nutrition (2001) 55, 444±451 ß 2001 Nature Publishing Group All rights reserved 0954±3007/01 $15.00 www.nature.com/ejcn Original Communication Complementary effects of Mediterranean diet and moderate red wine intake on haemostatic cardiovascular risk factors D Mezzano1*, F Leighton2, C MartõÂnez1, G Marshall3, A Cuevas4, O Castillo4, O Panes1, B MunÄoz1, DD PeÂrez2, C MizoÂn4, J Rozowski4, A San MartõÂn2 and J Pereira1 1 Department of Hematology-Oncology, School of Medicine, Catholic University of Chile, Santiago, Chile; 2Biochemical Cytology and Lipids Laboratory, Faculty of Biological Sciences, School of Medicine, Catholic University of Chile, Santiago, Chile; 3Department of Public Health, School of Medicine, Catholic University of Chile, Santiago, Chile; and 4Department of Nutrition, Diabetes and Metabolism, School of Medicine, Catholic University of Chile, Santiago, Chile Objectives: To compare the effect of alcohol-free Mediterranean-type diet (MD) and high-fat diet (HFD) on plasma concentration of emergent haemostatic cardiovascular risk factors (HCVRF). Also, to test if red wine supplementation modi®es HCVRF, independent of diet. Design, subjects and intervention: Controlled prospective intervention study. Two groups, each of 21 healthy male university students (22  3.4 y), received either MD or HFD for 90 days. Between days 30 and 60, both diets were supplemented with 240 ml=day of red wine. Baseline and T30, T60 and T90-day samples were drawn. No drop out from the study was observed. Setting: University campus and outpatient nutrition clinic. Results: Volunteers on HFD at T30 had increases in pro-coagulants ®brinogen (22%), factor VIIc (9%), and factor VIIIc (4%), and decreases in natural anticoagulants antithrombin III (3%), protein C (11%) and protein S (6%) and of 20% in plasminogen activator inhibitor-1. At the same time, individuals on MD had increases in ®brinogen (4%), antithrombin III (5%), protein C (3%), protein S (2.7%), and decreases in factor VIIIc (9%), and plasminogen activator inhibitor-1 (21%). After adjusting by baseline values, MD was associated with lower plasma ®brinogen (P ˆ 0.03), factor VIIc (P ˆ 0.034) and factor VIIIc (P ˆ 0.0057) and with higher levels of protein S (P ˆ 0.013). Red wine supplementation, in both diets, resulted in decreased plasma ®brinogen (P ˆ 0.001) and factor VIIc (P ˆ 0.05), and increased tissue plasminogen activator antigen (P ˆ 0.01) and plasminogen activator inhibitor-1 antigen (P ˆ 0.0003). Wine consumption was also associated with signi®cantly (P ˆ 0.01) divergent effects on antithrombin III: it decreased by 10% in individuals on HFD but increased slightly in those on MD. No effects of diet or wine were detected in plasma protein C and C-reactive protein. Conclusion: MD and moderate consumption of red wine have complementary, mostly bene®cial effects on HCVRF. Sponsorship: P Catholic University of Chile. Descriptors: diet; wine; haemostasis; cardiovascular risk factors European Journal of Clinical Nutrition (2001) 55, 444 ± 451 Introduction *Correspondence: D Mezzano, Haemostasis Laboratory, Department of Hematology-Oncology, School of Medicine, Catholic University, PO Box 114-D, Santiago, Chile. E-mail: Guarantor: D Mezzano. Contributors: DM, FL, GM, AC, JR and JP participated in the conception and design of the study, in the analysis and interpretation of data and in writing the article. CM and OC participated in clinical control of participants, diet design and daily supervision of the diet. CM, OP, BM and DP provided administrative, technical and logistic support and completed the experimental work. GM and ASM were responsible for statistical analysis. Received 25 August 2000; revised 22 January 2000; accepted 24 January 2001 Intervention and epidemiological studies show that some dietary habits and light-to-moderate alcohol consumption provide cardiovascular (CV) protection. A recent publication summarized these effects, indicating that foods of animal origin are directly correlated whereas vegetablefood groups, ®sh and alcohol are inversely correlated with coronary heart disease mortality (Menotti et al, 1999). Populations consuming a diet rich in vegetables, olive oil, ®sh and wine (Mediterranean diet, MD) had the lowest mortality among the seven countries included in that study. The bene®ts of this diet apparently can be transferred to populations of other ethnic origins (Kouris-Blazos Effects of Mediterranean diet D Mezzano et al et al, 1999) and have also been reproduced in secondary prevention trials (de Lorgeril et al, 1999). Alcoholic beverages, mostly wine, are a constitutive component of MD. Whether wine itself adds an independent CV bene®t to this diet is a matter of debate (de Lorgeril & Salen, 1999). Despite reports indicating that light to moderate alcohol consumption reduces CV mortality (Thun et al, 1997) and stroke (Berger et al, 1999), wine drinking has also been related with the intake of healthier diets (Tjonneland et al, 1999), and with other advantageous lifestyle characteristics (Wannamethee & Shaper, 1999). Thus, the proposal of Renaud et al that alcohol, speci®cally wine, is a major determinant of the bene®ts of MD (Renaud & de Lorgeril, 1992) needs to be demonstrated. Lower rates of CV disease and mortality in Southern European countries could be only partially explained by differences in fat intake or in blood lipid pro®les (Kromhaut, 1999). Accordingly, additional mechanisms, like changes in plasma levels of haemostatic factors, should contribute to this protection. Some of these factors have emerged as predictors for coronary heart disease (Ridker, 1997), furthermore, several reports indicate that these are modi®able by diet and alcohol (including wine). In fact, MD on the whole (Bijnen et al, 1996) or distinctive components of this diet, such as lower saturated fat consumption, as well as higher intakes of monounsaturated fatty acids, fruit and vegetables, (Westrate et al, 1998; Roche et al, 1998; Temme et al 1999; Mezzano et al, 1999) appears related to a more favorable pro®le of haemostatic cardiovascular risk factors (HCVRF). The same holds for alcohol or wine, as summarized in a recent meta-analysis which revealed that CV bene®ts of alcohol intake are mostly mediated through changes in blood lipids and HCVRF, mainly ®brinogen (Rimm et al, 1999). Figure 1 The aims of the current study were two-fold: ®rst, to compare the effects of two alcohol-free diets, an MD and a high-fat, Western-type diet (HFD) on HCVRF; second, to assess the changes in these factors after supplementing each diet with a moderate amount of red wine. 445 Subjects and methods Subjects and study design The subjects of this intervention study were 42 healthy undergraduate or graduate university male students aged 22  3.4 y, who gave informed consent to participate. Incorporation criteria included absence of clinical disease and obesity, serum lipids and gluco (...truncated)