Abnormal metabolism of shellfish sterols in a patient with sitosterolemia and xanthomatosis.

Abstract

Sitosterolemia and xanthomatosis together are a disease characterized by premature cardiovascular disease, and by elevated plasma concentrations of total sterols and of plant sterols, especially sitosterol which is hyperabsorbed. In order to determine whether this abnormal metabolism also involved other sterols, a patient with sitosterolemia was fed a diet high in shellfish that contain significant quantities of noncholesterol sterols, some of which are less well absorbed than cholesterol in humans. Compared with control subjects (n = 8), the sitosterolemic subject had an increased absorption of 22-dehydrocholesterol (71.5% vs. 43.8±11A%, mean±SD), C-26 sterol (80.6% vs. 493±11.4%), brassicasterol (51.8% vs. 4.8±4.2%), and 24-methylene cholesterol (60.5% vs. 16.0±8.3%). This enhanced absorption was associated with an increased plasma total shellfish sterol level (13.1 mg/dl vs. 1.9±0.7 mg/dl in normals). In the sitosterolemic subject, as in normals, the shellfish sterols were not preferentially concentrated in any lipoprotein class, and 50-65% of these sterols were in the esterified form in plasma. Bile acids and neutral sterols were quantitated in bile obtained by duodenal aspiration. The bile acid composition did not differ significantly in the sitosterolemic subject compared with the normal controls. The sitosterolemic subject, though, was unable to concentrate normally the neutral shellfish sterols in bile. The normal controls concentrated the shellfish sterols in bile 63±1.7-fold relative to the plasma shellfish sterol concentration whereas the study subject was only able to concentrate them 2.1-fold. We propose that sitosterolemia and xanthomatosis occur from a generalized abnormality in the usual ability of the gut mucosa and other tissues of the body to discriminate among many different sterols. This has important implications for the understanding of the pathophysiology of this disease and for therapeutic recommendations.

Inactivation of liver X receptor β leads to adult-onset motor neuron degeneration in male mice

“…The response of ABCG5 and ABCG8 to cholesterol requires the LXRs and treatment with a synthetic LXR agonist increases the sterol excretion by the ABCG5͞G8 route in vivo (43). Mutation in either of these transporters causes sitosterolemia, a rare recessive disorder with patients accumulating plantand shellfish-derived sterols from the diet in the blood and tissues (44,45). Plant sterols have been reported to accumulate in the brain of ABCG5-and ABCG8-deficient mice, although the extent of the accumulation was much lower than in the liver and plasma (46).…”

Current Therapy for Patients with Sitosterolemia –Effect of Ezetimibe on Plant Sterol Metabolism

“…For such a diet, fruits, vegetables and cereal products without germ may be used, while vegetable fats and all plant foods with high fats, such as vegetable oils, margarine, nuts, avocados, and chocolate, should be avoided. Since the metabolism of shellfish sterols is also impaired in sitosterolemia, shellfish should also be avoided 31) . While dietary therapy has been shown to decrease serum levels of plant sterols in patients with sitosterolemia, in most cases, the levels do not reach the normal range.…”

Phenotypic heterogeneity of sitosterolemia

“…However, patients with sitosterolemia fail to resecrete absorbed plant sterols, so that Ͼ 60% of ingested sitosterol is absorbed (4,(11)(12)(13)(14)(15). Furthermore, patients with sitosterolemia have a generalized hyperabsorption of dietary sterols, including cholesterol and shellfish sterols, leading to increases in plasma concentrations of cholesterol and plant sterols, such as sitosterol (16). Homozygotes have not only increased intestinal absorption but also impaired biliary excretion of sterols.…”