Cardiovascular Disease

Epidemiological studies support the idea that a diet rich in high carotenoid containing foods is associated with a reduced risk of heart disease (Kritchevsky 1999). A review of observational and intervention studies on beta-carotene and the risk of coronary heart disease found that seven cohort studies (Gaziano et al 1995b, Gey et al 1993, Knekt etal 1994, Manson etal 1991, Morris et al 1994, Rimm et al 1993, Street et al 1994) reported relative risks between 0.27 and 0.78 for high serum beta-carotene levels or high dietary intake and that this was supported by case-control studies (Bobak et al 1998, Bolton-Smith et al 1992, Kardinaal et al 1993, Torun et al 1994, Tavani et al 1997) that reported odds ratios between 0.37 and 0.71, with a possible stronger protection for current smokers (Tavani & La Vecchia 1999). These results contrast with those of four more recent cohort studies (Knekt et al 1994, Kushi et al 1996, Pandey et al 1995, Todd et al 1995) and five large RCTs (Buring et al 1996, Hennekens et al 1996a, Lee et al 1999, Redlich et al 1999, Vlot et al 1995) that have not reported any significant prevention of cardiovascular disease with beta-carotene supplementation.

The final results of the Physicians' Health Study (see Cancer Prevention above) indicated that beta-carotene supplementation had no significant benefit or harm on cancer or cardiovascular disease during more than 12 years of treatment (Hennekens et al 1996). Similarly, the results of the Women's Health Study, which involved 39,876 women aged 45 years or older, found that beta-carotene supplementation of 50 mg on alternate days did not influence cardiovascular disease after 2 years of supplementation and 2 years of further follow-up. Subgroup analysis revealed an apparent benefit of beta-carotene supplementation on subsequent vascular events among 333 men with prior angina or revascularisation (Christen et al 2000).

In contrast, analysis of the data from the ATBC cancer prevention study, which involved 23,144 male smokers, found that beta-carotene supplementation slightly increased the risk of angina (Rapola et al 1996) and intracerebral haemorrhage while having no overall effect on the risk of stroke (Leppala et al 2000a,b), abdominal aortic aneurysm (Tornwall et al 2001), or symptoms and progression of intermittent claudication (Tornwall et al 1999). Beta-carotene, however, was found to decrease the risk of cerebral infarction modestly among a subgroup with greater alcohol consumption (Leppala etal 2000a,b). In a 6-year post-intervention follow-up study, beta-carotene was found to increase the risk of first-ever myocardial infarction while continuing to have no overall effect on the incidence of stroke (Tornwall et al 2004). An analysis of 52 men from the CARET Study concluded that there was no significant effect on total, HDL- or LDL-cholesterol levels that could account for the observed increase risk of cardiovascular disease observed in this study (Redlich et al 1999).

A pooled analysis of four randomised trials of beta-carotene therapy ranging from 20 mg to 50 mg involving 90,054 patients found beta-carotene supplementation to be associated with a significant increase in all-cause mortality and cardiovascular death in patients at risk for coronary disease, with the increased risk being strongest in smokers. A further meta-analysis of eight randomised trials involving 138,113 patients found that supplementation with 15-50 mg of beta-carotene was associated with a small but significant increase in all-cause mortality and a slight increase in cardiovascular death (Vivekananthan et al 2003).

The apparent discrepancy between the findings of observational and intervention studies may be due to several factors, including the length and nature of the intervention (Tavani & La Vecchia 1999). For example the intervention trials involved supplementation with synthetic beta-carotene in isolation or with other single nutrients, whereas the observational studies involved the consumption of beta-carotene-rich foods containing a range of additional antioxidant vitamins, Beta-carotene 94

phytonutrients and micronutrients.

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