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Objective: To test the dose-response effect on low-density lipoprotein cholesterol (LDL-c) of plant sterols (PS) from different sources in a low-fat spread. Methods: Dose responses of soybean oil (BO), tall oil (TO) and a mix of tall oil and rapeseed oil (TO/RP) as fatty acid esters were tested in a parallel design in free-living subjects recruited from the general community who had elevated cholesterol concentrations. Subjects received either control for 6 weeks or 1.6 g PS per day for 3 weeks, then 3.0 g/day for 3 weeks. Results: LDL-c was lowered significantly by consumption of 1.6 g/day of PS (À10.4%, range À7.3 to À11.4%). Increasing the dose to 3.0 g/day modestly reduced LDL-c concentrations further to À14.7%. TO, containing 78% sitosterol, produced an increase in serum sitosterol of 6.5 nmol/ml, while BO, containing only 27% campesterol, produced an increase in serum campesterol of 9.5 nmol/ml in 6 weeks. After PS withdrawal, serum sterols declined by 50% within 2 weeks. Conclusion: Different PS sources were equally effective in lowering serum LDL-c concentrations. The decrease in absolute concentrations of LDL-c was dependent on the baseline concentrations. IntroductionA large number of human intervention studies have been performed using plant sterols (PS) or stanols incorporated into different food matrices to study their cholesterollowering effects. These studies are based on unesterified (free) or esterified PS or stanols, where the esterification is mostly based on vegetable-oil-derived fatty acids. Since the first publications of Mattson et al. in 1977 and1982, in which the efficacy of the ester format was shown, the interest in enriching foods with PS or stanol esters as an effective means of lowering total cholesterol (TC) and lowdensity lipoprotein-cholesterol (LDL-c) has increased. Quite a number of different food formats are now available, such as spreads, yogurts or milks, which can be taken on a daily basis. These foods formats typically provide between 1.5 and 2.5 g/day of PS or stanols from one or more servings, which have been proven to result in a 10-15% LDL-c lowering.From these studies considered collectively, the effective dose range can be established. It was stated in a recent metaanalysis of 41 studies that increasing the dose of PS or stanols to above 2.5 g/day results in little additional effects on lowering cholesterol (Katan et al., 2003). A few studies using specific PS sources and formats have also shown a dose response in smaller groups (Weststrate and Meijer, 1998;Hendriks et al., 1999). However, these studies were based on parallel groups or random assignment to the order of PS dose. One study has examined using PS the effect of four Correspondence: Dr PM Clifton, CSIRO Human Nutrition, Gate 13 Kintore Ave, Adelaide, SA 5000, Australia. E-mail: peter.clifton@csiro.au Guarantor: PM Clifton. Contributors: PMC and GSMJED designed the study; the intervention part was organized and monitored by PMC. PMC and MM coordinated the serum analysis. HCMvdK performed the data analysis ...

Iodine deficiency is now recognized as a major international public health problem. It is estimated that 800 million people may be at risk of the effects of iodine deficiency. In humans, the effects occur at all stages of development: the fetus, the neonate, the child and adult. The effects are now denoted by the term iodine deficiency disorders (IDD). They include miscarriages, stillbirths, congenital anomalies, as well as the more familiar goiter, cretinism, impaired brain function, and hypothyroidism in children and adults. In domestic animals, reproductive failure has been reported with the production of aborted, stillborn and weak calves. Experimental studies in animal models have been reviewed to provide evidence of the mechanisms involved, particularly in relation to brain development. The findings in three different species (rat, sheep, monkey) indicate that the effects are mediated by a combination of maternal and fetal hypothyroidism, the effect of maternal hypothyroidism being earlier than the onset of fetal thyroid secretion. The findings suggest that iodine deficiency has an early effect on neuroblast multiplication and, if so, this could be important in the pathogenesis of the neurological form of endemic cretinism. The assessment of the full effects of iodine deficiency on the brain requires further studies in the postnatal period to determine the duration of these effects.

Sheep have been used to study the effect of dietary iodine deficiency on the development of the fetal brain. Severe iodine deficiency caused reduction in fetal brain and body weights and in brain DNA and protein from 70 days gestation to parturition. The lowered brain weight and brain DNA at 70 days gestation indicates a reduced number of cells, probably due to slower neuroblast multiplication which normally occurs from 40-80 days in the sheep, and the reduction in DNA and protein after 80 days implies that the development of neuroglia could be slowed also in iodine deficiency. Morphological changes were observed in both the cerebral hemispheres and the cerebellum. In the cerebral hemispheres of the iodine-deficient fetuses an increased density of neurons was apparent histologically in the motor cortex and visual cortex and in the CA1 and CA4 areas of the hippocampus in comparison with controls. In the cerebellum there was delayed migration of cells from the external granular layer to the internal granular layer and increased density of Purkinje cells in the iodine-deficient fetal brains. In addition, the molecular area was increased and the medullary area reduced in comparison with controls. These change are indicative of delayed brain maturation. Evidence of fetal hypothyroidism was provided by low fetal thyroid iodine and plasma T4 values, thyroid hyperplasia from 70 days gestation, significant reduction in body weight at the same time as the brain retardation, and absence of wool growth and delayed skeletal maturation near parturition. It is apparent from the biochemical and histological changes observed during iodine deficiency that iodine is an essential element for normal fetal brain and physical development in the sheep.