Safety evaluation of certain food additives - ipcs inchem

PHYTOSTEROLS, PHYTOSTANOLS AND THEIR ESTERS 145
In a single-blind study, 35 mildly hypercholesterolaemic subjects consumed
high levels of phytosterol esters in fat spread and muesli for 6 weeks. Total
consumption at full compliance summed up to 6.6 g phytosterols/day. Baseline
measurements of serum lipids, phytosterols, carotenoids and fat-soluble vitamins
in plasma were undertaken during a 2-week baseline period preceding the
treatment. Cholesterol-adjusted plasma concentrations of -carotene, -carotene,
lutein and lycopene decreased by 20%, 26%, 14% and 11%, respectively,
compared with baseline. Lutein and -carotene concentrations, but not -carotene
concentrations, increased significantly upon diet supplementation with fruits and
vegetables. Carotenoid-lowering effects were partly reversible during a 2-week
wash-out period. Vitamin A and D levels were not affected by phytosterol ester
treatment. After the consumption of the high phytosterol ester diet, -sitosterol and
campesterol plasma concentrations were increased by 45% and 105%, respectively
(Clifton et al., 2004).
A study investigated whether increased -carotene intake is able to impede
the decrease of -carotene plasma levels induced by phytosterol uptake. In a
double-blinded cross-over study with 46 individuals, whose diet was supplemented
with fruits and vegetables, -carotene plasma levels of individuals receiving 2.3 g
phytosterol esters per day or 2.5 g phytostanol esters per day were similar to those
of controls when -carotene levels were normalized to blood lipids, but not with
absolute plasma levels (Noakes et al., 2002).
No differences in plasma levels of -carotene, -tocopherol or other
antioxidants were detected between a control group and a group ingesting 3.2 g
phytosterols/day as phytosterol esters in bakery products enriched with tocopherol
(5.3 mg/day) and -carotene (0.9 mg/day) for 8 weeks. In this study,
consumption of phytosterol esters increased -sitosterol plasma levels by 89%
(Quílez et al., 2003).
2.5.3 Association with atherosclerosis
The observation that increased uptake and plasma levels of phytosterols
lead to premature atherosclerosis in patients with phytosterolaemia raised concerns
about a possible atherosclerotic activity of phytosterols in the general population
(Patel & Thompson, 2006; John et al., 2007).
In a review of 45 studies (population-based studies and clinical trials),
baseline plasma concentrations of phytosterols were derived. Plasma concentrations
ranged between 2.8 and 16.0 μmol/l (mean 7.9 ± 2.7 μmol/l) for -sitosterol
and between 6.9 and 27.9 μmol/l (mean 14.2 ± 5 μmol/l) for campesterol. From a
subset of these studies, the authors concluded that supplementing the diet with
1.8–2 g phytosterols/day for 4–8 weeks results in a 52–99% increase in campesterol
levels and in a 23–93% increase in -sitosterol levels. Supplementation of the diet
with phytostanols at dose levels of 1.5–3 g/day decreased phytosterol plasma
concentrations (Chan et al., 2006).
An analysis of 11 clinical trials with consumption of phytosterols in fat
spread in a range of 1.6–3.3 g/day revealed increases of campesterol in plasma of
30–120% (with one exception, where a phytosterol mixture containing only low