Phytosterols are cholesterol-like molecules found in all plant foods, with the highest concentrations occurring in vegetable oils. They are absorbed only in trace amounts but inhibit the absorption of intestinal cholesterol including recirculating endogenous biliary cholesterol, a key step in cholesterol elimination. Natural dietary intake varies from about 167-437 mg/day. Attempts to measure biological effects in feeding studies have been impeded by limited solubility in both water and fat. Esterification of phytosterols with long-chain fatty acids increases fat solubility by 10-fold and allows delivery of several grams daily in fatty foods such as margarine. A dose of 2 g/day as the ester reduces low density lipoprotein cholesterol by 10%, and little difference is observed between Delta(5)-sterols and 5alpha-reduced sterols (stanols). Phytosterols can also be dispersed in water after emulsification with lecithin and reduce cholesterol absorption when added to nonfat foods. In contrast to these supplementation studies, much less is known about the effect of low phytosterol levels in the natural diet. However, reduction of cholesterol absorption can be measured at a dose of only 150 mg during otherwise sterol-free test meals, suggesting that natural food phytosterols may be clinically important. Current literature suggests that phytosterols are safe when added to the diet, and measured absorption and plasma levels are very small. Increasing the aggregate amount of phytosterols consumed in a variety of foods may be an important way of reducing population cholesterol levels and preventing coronary heart disease.

The Elecsys β-amyloid (1-42) assay has high analytical performance that may improve biomarker-based AD diagnosis.

D-chiro-Inositol is a rare inositol isomer present in inositol phosphoglycans which are proposed mediators of insulin action. To study D-chiro-inositol metabolism in diabetes mellitus, a sensitive and specific assay was developed using negative-ion chemical ionization gas chromatography/mass spectrometry. Median urinary D-chiro-inositol excretion, which was 2.1 ,umol/day in nondiabetics, was substantially increased to 12 ,umol/day in non-insulin-dependent diabetes (P < 0.0001) and to 74 j,mol/day in insulin-dependent diabetes (P < 0.0001). Urinary D-chiro-inositol was strongly correlated with fasting plasma glucose (r = 0.568, P < 0.0001), glycated hemoglobin (r = 0.529, P < 0.0001), and urinary glucose (r = 0.368, P = 0.01). The renal clearance of D-chiro-inositol was selectively elevated in both non-insulin-dependent and insulindependent diabetes when compared with the clearances of L-chiro-inositol or myo-inositol and exceeded the glomerular filtration rate in 71% of the diabetics but in none of the nondiabetics. In poorly controlled diabetic patients insulin treatment reduced urinary D-chiro-inositol losses by 63% and increased plasma levels by 8.8-fold. The metabolism of D-chiroinositol is abnormal in diabetes and appears to be influenced by short-and long-term metabolic control.One of the most important problems in endocrinology is the rigorous description of the mechanism of insulin action. Previous work suggests that some (but not all) of the actions of insulin may be mediated through inositol phosphoglycan molecules released from cell membranes (1-4). When such putative mediators were hydrolyzed and analyzed chemically it was found unexpectedly that in some preparations much or all of the inositol present was not myo-inositol (which is, by far, the most common mammalian inositol) but rather the rare epimer D-chiro-inositol (5, 6). Kennington et al. (7) reported abnormally low or unmeasurable levels of D-chiro-inositol in urine and muscle from patients with non-insulin-dependent diabetes mellitus (NIDDM) and suggested that D-chiroinositol deficiency might be related to the insulin resistance observed in NIDDM.However (9) and urinary albumin (Diagnostic Products, Los Angeles) were determined by radioimmunoassay, and glycated hemoglobin was determined by affinity chromatography (Pierce; normal range 4.4-6.3%).Inositol Analysis. Twenty-four-hour urine specimens were collected with cooling but without preservatives and aliquots were stored frozen at -20°C. D-chiro-Inositol levels changed <3% after incubation of nonsterile urine from two poorly controlled diabetics and two normal subjects for 24 hr at 25°C, indicating that urinary D-chiro-inositol levels are stable during collection. To 0.25 ml of urine were added 10 nmol of deuterated DL-chiro-inositol and 20 nmol of deuterated myoinositol as internal standards. The samples were then purified by a modification of a procedure (7) in which the sample was first passed over a 0.6-ml column of water-washed Amberlite IR-120(+) (Aldrich) and then over a 0....

Our objective was to measure the systemic absorption of lecithin-emulsified ⌬ 5 -phytosterols and phytostanols during test meals by use of dual stable isotopic tracers. Ten healthy subjects underwent two single-meal absorption tests in random order 2 wk apart, one with intravenous dideuterated ⌬ 5 -phytosterols and oral pentadeuterated ⌬ 5 -phytosterols and the other with the corresponding labeled stanols. The oral-to-intravenous tracer ratio in plasma, a reflection of absorption, was measured by a sensitive negative ion mass spectroscopic technique and became constant after 2 days. Absorption from 600 mg of ⌬ 5 -soy sterols given with a standard test breakfast was 0.512 Ϯ 0.038% for sitosterol and 1.89 Ϯ 0.27% for campesterol. The absorption from 600 mg of soy stanols was 0.0441 Ϯ 0.004% for sitostanol and 0.155 Ϯ 0.017% for campestanol. Reduction of the double bond at position 5 decreased absorption by 90%. Plasma t½ for stanols was significantly shorter than that for ⌬ 5 -sterols. We conclude that the efficiency of phytosterol absorption is lower than what was reported previously and is critically dependent on the structure of both sterol nucleus and side chain.

Sitostanol reduced cholesterol absorption at doses lower than reported previously, but only if presented in lecithin micelles. Properly formulated sitostanol as well as naturally occurring complexes of phytosterol and phospholipid might be therapeutically useful for cholesterol lowering.

We measured plasma leptin concentrations by RIA in 204 normal weight and obese subjects, aged 18-80 yr, using full-length recombinant human leptin as a standard. Fasting levels between 1.2-97.9 ng/mL were observed. The plasma leptin concentration was highly correlated with percent body fat (r = 0.710; P < 0.0001) and was 3 times as high in women as in men (17.1 vs. 5.8 ng/mL; P < 0.0001). Circulating leptin was inversely related to age and was reduced 53% in subjects over age 60 yr. A statistical model containing percent body fat, gender, and age accounted for 65% of the variance in plasma leptin levels. Leptin was not independently related to abdominal fat distribution, plasma lipids and lipoproteins, chronic energy intake, diet composition, plasma insulin, or maximum oxygen consumption. However, plasma leptin was reduced by 26% in 5 obese subjects who consumed a 1000-Cal diet for 10 days (P = 0.004). We conclude that circulating leptin rises continuously with increasing adiposity. Gender, age, and short term caloric restriction may be important secondary regulators of plasma leptin.

Phytosterols effectively reduce LDL-cholesterol when given as supplements, and the smaller amounts in natural foods also appear to be important. Future work will focus on the better delivery of phytosterols in natural foods and supplements and on further defining the mechanisms of action.

Phytosterols comprising < 1% of commercial corn oil substantially reduced cholesterol absorption and may account for part of the cholesterol-lowering activity of corn oil previously attributed solely to unsaturated fatty acids.