The effects of oral vitamin supplementation on cardiovascular risk factors
BY J. V. WOODSIDE, I. S. YOUNG, J. W. G. YARNELL, D. McMASTER, A. E. EVANS
[excerpted from the Proceeding of the Nutrition Society (1997), 56, 479-488, University of Ulster at Coleraine on 24-28 June, 1996]
CHD (Coronary Heart Disease) causes approximately half the deaths among middle-aged adults in the industrialized world. However, major accepted risk factors combined can explain only about 50% of heart disease (Editorial, 1984). The possible aetiological involvement of novel risk factors, therefore, is receiving much attention.
The present review focuses on two such risk factors: hyperhomocysteinaemia (elevated homocystein levels) and LDL oxidation. Both these factors can be linked with inadequate vitamin intake and, therefore, may be amenable to nutritional intervention (Selhub et al. 1993; Jha et al. 1995).
Homocysteine is a Sulfur-containing amino acid which is an intermediary product in methionine metabolism (Finkelstein, 1990). Recent investigations have focused on the possibility that moderate elevations may be associated with increased risk of vascular disease (McCully, 1983). To date, more than twenty clinical studies involving over 2000 patients with cardiovascular disease and a similar number of controls have shown that patients tend to have higher homocysteine levels, even though in most cases values are within the accepted normal range (Malinow, 1990; Kang et al. 1992; Ueland et al. 1992).
Several retrospective and cross-sectional studies have linked premature vascular disorders including CHD, cerebral and peripheral vascular disease with elevated homocysteine levels (Malinow, 1990; Clarke et al. 1991; Malinow et al. 1993; Boushey et al. 1995). In addition, the association between hyperhomocysteinaemia and cardiovascular disease has been confirmed in several large prospective studies (Taylor et al. 1991; Stampfer et al. 1992; Verhoef et al. 1994; Arnesen et al. 1995; Perry et al. 1995) with only one study showing no association (Alfthan et al. 1994). In the Physicians’ Health Study, a total of 14916 US male physicians aged 40 to 84 years were followed up for 6 years. Men with homocysteine levels above the 95th percentile (based on control, distribution) had a three-fold increased risk of myocardial infarction compared with those in the bottom 90 % (Stampfer et al. 1992). The findings were also statistically compatible with a graded risk increase across the distribution, a suggestion confirmed by Perry et al. (1995) in a prospective study of stroke in middle-aged British men. Similar findings have been reported for myocardial infarction (Arnesen et al. 1995), carotid-artery thickening (Malinow et al. 1993) and angiographically-defined coronary artery stenosis (Genest et al. 1990). In addition, Selhub et al. (1995) demonstrated a gradual increase in the prevalence of carotid artery stenosis with increasing levels of homocysteine. Meta-analysis by Boushey et al. (1995) showed an increase in risk of coronary artery disease of about 70 % for each 5 umol/l rise in fasting homocysteine.
Several mechanisms are likely to be involved in the induction of vascular disease by homocysteine, including endothelial cell desquamation (Harker et al. 1974; Starkebaum & Harlan, 1986), oxidation of LDL (Heinecke et al. 1987; Parthasarathy, 1987; Blom et al. 1995), and monocyte adhesion to the vessel wall (Kottke-Marchant et al. 1990). Additional roles for homocysteine in haemostasis and atherogenesis have been suggested but not confirmed. Early studies showed that in hyperhomocysteinaemic patients, platelet turnover was increased (Harker et al