Safety evaluation of certain food additives - ipcs inchem

PHYTOSTEROLS, PHYTOSTANOLS AND THEIR ESTERS 139
17-Estradiol was used as a positive control. Precipitation and slight cytotoxicity
were observed at the highest concentration with all mixtures. No cell proliferation
was observable in cells treated with phytostanols. Under the conditions of this study,
the phytostanol mixtures tested showed no estrogenic activity (Leeman, 1998).
The uterotrophic activity of WDPSE and VODPSE was investigated in vivo
in a short-term test with young female rats (aged 17 days) (Tiecco test). Groups of
10 female Wistar rats were fed diets containing 0% or 8.3% WDPSE or 8.3%
VODPSE for 4 days. Diethylstilbestrol at concentrations of 5, 10 or 20 μg/kg in the
diet was used as positive control. Uterus weight was used as an indicator of
estrogenic activity. No treatment-related effects on the animals’ general condition,
body weight or food consumption were observed. Neither WDPSE nor VODPSE
treatment influenced the uterus weights of the animals at the end of the treatment
period (Jonker, 1997).
2.5 Observations in humans
2.5.1 Lipid-lowering effect
The lipid-lowering effect of phytosterols and phytostanols was investigated
in numerous human studies. In 2001, 32 experts convened in Stresa, Italy, to
discuss the outcome of 42 human randomized, placebo-controlled trials available
up to then (Katan et al., 2003). Study duration was typically several weeks, and
doses of phytosterols or phytostanols (either esterified or in free form) were up to
3.4 g/day. In an analysis of the pooled data, the authors concluded that at mean
doses of 2.5 g stanols/day and 2.3 g sterols/day, LDL cholesterol decreased in
adults by 10.1% (95% confidence interval [CI] = 8.9–11.3%) and 9.7% (95% CI =
8.5–10.8%), respectively, with no statistical differences in the effect of phytosterols
compared with phytostanols. In agreement with older studies, the dose–effect
relationship reached a plateau at intake levels of about 2 g/day, with higher doses
showing no increased effect. The SCF concluded from studies reviewed that the
“blood [total cholesterol- and LDL cholesterol-]lowering effect of sterols and stanols
is quite similar, although the hydrogenated sterol esters may be somehow more
efficient in reducing the intestinal absorption of cholesterol” (Scientific Committee
on Food, 2002).
2.5.2 Effects on vitamins and carotenoids
Several human studies showed that ingestion of phytosterols and
phytostanols led to reduced serum levels of carotenoids, but not retinol (vitamin A).
It is assumed that, as with cholesterol, the concentration of other lipophilic
compounds such as provitamins and antioxidants in mixed micelles and
consequently their uptake are reduced by phytosterols and phytostanols (Plat &
Mensink, 2005). As carotenoids and tocopherols in blood are mainly bound to HDL,
LDL and very low density lipoprotein (VLDL), their serum concentrations are often
adjusted to lipid content (either as blood total cholesterol or as LDL cholesterol
levels) to account for changes in their carriers. Decreases in serum carotenoids and
-tocopherol observed in these studies generally disappeared after standardization
for lipid content, with the exception of -carotene.