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Background Data from previous studies are inconsistent, and it is therefore uncertain whether, to what extent, and at what level leisure physical activity influences the risk of osteoporotic fractures in [...]

Alkylresorcinols (ARs) are phenolic lipids present in whole grain and bran of wheat and we. Chemically, they comprise 1,3dihydroxy-5-alkylbenzene homologs with odd-numbered, mainly saturated hydrocarbon side chains in the range of 17-25 carbon atoms. ARs are evaluated both for physiological effects and for their potential use as biomarkers of whole-grain wheat and we intake. In this study, plasma kinetics and relative bioavailability of ARs in humans were investigated after a single intake of we bran 120 g (190 mg ARs). The shapes of plasma concentration time curves were similar in the subjects (n = 6) with 2 peaks at ~2.8 and 6.5 h and maximum concentrations (mean [+ or -] SEM) of 1253 [+ or -] 125 and 3365 [+ or -] 309 nmol/L, respectively. The relative bioavailability of different homologs increased with increasing length of the AR side chain (r = 0.97, P < 0.001), indicating differences in metabolism. The apparent half-lives were rather short, ~5 h for all homologs, which suggests that the AR concentration in plasma could be used as a short- to medium-term biomarker of regular intake of whole-grain wheat and rye.

(n-3) Fatty acids are unsaturated and are therefore easily subject to oxidization; however, they have several beneficial health effects, which include protection against cardiovascular diseases. The aim of this study was to investigate whether (n-3) fatty acids, with a controlled fat quality in the background diet, affect nonenzymatic and enzymatic lipid peroxidation and antioxidant status in humans. A total of 162 men and women in a multicenter study (The KANWU study) were randomly assigned to a diet containing a high proportion of saturated fatty acids or monounsaturated fatty acids (MUFA) for 3 mo. Within each diet group, there was a second random assignment to supplementation with fish-oil capsules [3.6 g (n-3) fatty acids/d] or placebo. Biomarkers of nonenzymatic and enzymatic lipid peroxidation in vivo were determined by measuring 8-iso-prostaglandin [F.sub.2[alpha]] (8-iso- [PGF.sub.2[alpha]]) and prostaglandin [F.sub.2[alpha]] ([PGF.sub.2[alpha]]) concentrations in plasma at baseline and after 3 mo. Antioxidant status was determined by measuring plasma antioxidant capacity with an enhanced chemiluminescence assay. The plasma 8-iso-[PGF.sub.2[alpha]] concentration was significantly decreased after 3 mo of supplementation with (n-3) fatty acids (P = 0.015), whereas the [PGF.sub.2[alpha]] concentration was not affected. The antioxidant status was not affected by supplementation of (n-3) fatty acids, but was improved by the background diet with a high proportion of MUFA. We conclude that supplementation with (n-3) fatty acids decreases nonenzymatic free radical--catalyzed isoprostane formation, but does not affect cyclooxygenase-mediated prostaglandin formation. KEY WORDS: * isoprostanes * prostaglandins * fatty acids * oxidative stress * antioxidant status

A predominance of small dense LDL (sdLDL) particles is a well-established component of the atherogenic lipoprotein phenotype associated with insulin resistance and increased risk for coronary heart disease. However, the influence of diet on LDL particle size distribution is not clear. We investigated (cross-sectionally) the relations between LDL profile and dietary fatty acids (FAs) in 291 healthy men (62-64 y old) with a range of insulin sensitivities. Individuals completed a 7-d dietary record, and fasting plasma insulin, lipid, and lipoprotein concentrations as well as serum and adipose tissue FA composition were determined. The LDL profile was examined by polyacrylamide gradient gel electrophoresis, protein-staining, and quantitative scanning, giving LDL peak particle size and the percentage distribution of LDL in 4 subfractions. The men were divided into tertiles of percentage distribution of sdLDL. Small dense LDL was positively related to plasma triacylglycerol and fasting insulin concentrations (both P < 0.0001) and inversely related to HDL cholesterol (P < 0.0001). No strong relations were found between sdLDL and the reported intake of SFA, monounsaturated fatty acids, or PUFA. However, individual FAs typically found in milk products were associated with a more favorable LDL profile (i.e., fewer sdLDL particles). This was shown for 4:0-10:0 and 14:0 in the diet (both P < 0.05), 15:0 and 17:0 in serum phospholipids (both P < 0.05), and 15:0 in serum nonesterified FAs (P < 0.01). Furthermore, 20:3(n-6) in adipose tissue and serum phospholipids was positively related to sdLDL. Therefore, LDL particle size distribution appears to be modified by dietary factors with an apparently beneficial effect of milk products. KEY WORDS: * small dense LDL * diet * milk fatty acids * fatty acid composition * healthy men

Increased intestinal viscosity appears to be the major mode of action by which dietary oat [beta]-glucan increases the fecal excretion of bile acids and thereby lowers blood cholesterol concentrations. The objective of this experiment was to investigate whether there is a difference in effects on blood lipids between two yeast-leavened oat bran breads containing [beta]-glucan (6 g/d) of low or high average molecular weight (HMW) (217 or 797 kDa, respectively). The breads were fed to 22 volunteers (women, n = 11; men, n = 11) in a randomized, double-blind, crossover design. The participants are one bread for 3 wk as part of their normal diet and switched breads after a 2-wk washout period. Blood samples were drawn from fasting subjects and analyzed for lipids, insulin, glucose, and [alpha]- and [gamma]-tocopherol. The two experimental oat breads did not differ in their effects on any of the variables measured. Compared to baseline, however, consumption of HMW bread increased serum insulin by 22.6% (P < 0.03) and decreased blood glucose concentrations by 3.4% (P < 0.05). These results suggest that the molecular weight, when [beta]-glucan is consumed in oat bran breads as part of the habitual diet, does not play an important physiological role in moderately hypercholesterolemic humans. J. Nutr. 134: 1384-1388, 2004. KEY WORDS: * [beta]-glucan * oat bran bread * soluble fiber * blood lipids * humans

Alkylresorcinols (AR) are a class of amphiphilic phenolic lipids present in high amounts in wheat and rye bran. They have been reported to be both growth retarding and innocuous when fed to rats, and to have a broad range of bioactivities in vitro, suggested to be related to their ability to bind to proteins and modify membranes. This study was designed to test the effects of AR (purified from rye bran) on growth, tocopherol levels, and cholesterol levels in rats. Rats were fed 1 of 4 different levels of AR for 4 wk: 0 (control), 1, 2, and 4 g/kg diet. AR did not affect final body, liver, or lung weights. The AR diets increased the levels of [gamma]-tocopherol in liver and lungs (P < 0.05). To investigate whether AR could have increased [gamma]-tocopherol levels via inhibition of tocopherol-[omega]-hydroxylase, HepG2 cells were incubated with AR and the metabolism of [gamma]-tocopherol measured. AR significantly inhibited the conversion of [gamma]-tocopherol to its water-soluble hydroxychroman metabolite in vitro, indicating that AR may increase [gamma]-tocopherol levels via inhibition of tocopherol metabolism in vivo. The 4 g AR/kg diet decreased liver cholesterol (P < 0.001), but did not affect plasma lipids. AR were detected in the perirenal adipose tissue samples of rats fed AR, indicating that they can accumulate in the fatty tissues of rats. High levels of dietary AR moderately affect [gamma]-tocopherol, possibly via inhibition of tocopherol metabolism, and decrease liver cholesterol in rats. KEY WORDS: * alkylresorcinols * cholesterol * cytochrome P450 * [gamma]-tocopherol * tocopherol-[omega]-hydroxylase

The effects of dietary (+)-catechin (CAT) and BHT on plasma and tissue concentrations of [alpha]-to-copherol ([alpha]-T), [gamma]-tocopherol ([gamma]-T) and cholesterol (C) were studied in male Sprague-Dawley rats. The rats were fed the compounds during a 4-wk period at concentrations of 2 g/kg in standardized diets, low but adequate in vitamin E, with 2 g/kg cholesterol. The CAT-regimen did not affect weight gain, feed intake or organ weights. BHT did not affect feed intake but lowered the body weight and the amount of liver lipids and increased the weights of livers and lungs relative to the body weight. Rats consuming CAT had 2.5-3.5-fold increased plasma, liver and lung [alpha]-T concentrations, but C concentrations remained unchanged. BHT-feeding resulted in 2.4- and 1.7-fold elevation in [alpha]-T but ~50% decrease in [gamma]-T concentrations in blood plasma and liver, respectively. BHT also lowered total C in the liver without affecting the concentration of C in the liver lipids. To investigate whether the [alpha]-T-sparing action of the studied compounds was due to the inhibition of tocopherol-[omega]-hydroxylase, HepG2 cells were incubated with CAT or BHT in the presence of [delta]-tocopherol ([delta]-T) and the 3' - and 5'-[delta]-carboxychromanol metabolites in the media were analyzed by GC/MS. Neither CAT nor BHT inhibited tocopherol-[omega]-hydroxylase activity in hepatocyte cultures; CAT was also inactive in a rat microsomal assay. In conclusion, both dietary CAT and BHT markedly increased [alpha]-T concentrations in plasma and organs of Sprague-Dawley rats by a mechanism that apparently does not involve inhibition of tocopherol-[omega]-hydroxylase, a key enzyme in tocopherol catabolism. J. Nutr. 133: 3195-3199, 2003. KEY WORDS: * BHT * catechin * cytochrome [P.sub.450] * tocopherols * tocopherol-[omega]-hydroxylase.

Too much vitamin A can increase a person's risk of bone fracture, according to a study of 2,322 men. Men with the highest blood levels of vitamin A had 7 times the risk of fracturing a bone compared to men with the lowest blood levels. On the other hand, beta carotene was not associated with an increased risk of bone fracture.

Local desaturation-elongation of linoleic acid, uptake of 2-arachidonyl-lysophosphatidylcholine, and uptake plasma unesterified arachidonic acid (AA) are assumed to be the most important sources of AA for extrahepatic tissues. In this study, we investigated the clearance rate as well as the retention rate of plasma unesterified [sup.14]C-AA in different tissues in fed rats. The initial half-life of [sup.14]C-AA in rat plasma was 3.8 s, and the average pool size of rat plasma unesterified AA was 76 nmol. We calculated that 604 nmol of unesterified AA was cleared from the rat plasma per minute. The retention rate of AA per gram of tissue in the heart (13 nmol/min per g), lungs (12 nmol/min per g), kidney (8 nmol/min per g) and bone marrow (6 nmol/min per g) was higher than that in other tissues but was lower than that in liver (23 nmol/min per g). The total uptake was highest in skeletal muscle (249 [+ or -] 27 nmol/min), in liver (226 [+ or -] 15 nmol/min) and in bone marrow (39 [+ or -] 3 nmol/min). More than 80% of retained [14.sup]C-AA was found in phospholipids in most tissues. The conclusion is that despite the low concentration plasma unesterified, AA is a major source of phospholipid AA in several extrahepatic tissues in rats, due to its rapid turnover and selective acylation into phospholipids. KEY WORDS: * arachidonic acid * clearance * free fatty acids * retention rate * tissue uptake

Lipid peroxidation is thought to be an important factor in the pathophysiology of a number of diseases and in the process of aging. We investigated the effects of supplementation with vitamin E on lipid peroxidation in rats. Both free radical-induced nonenzymatic- and cyclooxygenase-catalyzed enzymatic lipid peroxidation were investigated by measuring the levels of F(sub 2)-isoprostanes (8-iso-PGF(sub 2 alpha)) and PGF(sub 2 alpha)-metabolite (15-K-DH-PGF(sub 2 alpha), respectively, in blood, urine and liver. Samples were collected from control rats (n = 6) and from rats supplemented with vitamin E in the diet for 3 wk (n = 8, 20 g/kg diet of DL-(alpha)-tocopherol hydrogen succinate). Plasma (alpha)-tocopherol concentration and antioxidative capacity were greater in the vitamin E-supplemented rats than in the control rats (17.9 +/- 1.7 vs. 50.4 +/- 10.4 (mu)mol/L, P < 0.001 and 181 +/- 6 vs. 275 +/- 27 (mu)mol/L trolox equivalents, P < 0.001). Urine 8-iso-PGF(sub 2 alpha) tended to be lower in the vitamin E-supplemented rats (0.72 +/- 0.40 vs. 0.34 +/- 0.19 nmol/mmol creatinine, P = 0.056). Urine 15-K-DH-PGF(sub 2 alpha) was lower due to vitamin E supplementation (0.97 +/- 0.38 vs. 0.56 +/- 0.21 nmol/mmol creatinine, P < 0.05), as was liver-free 8-iso-PGF(sub 2 alpha) concentration (0.47 +/- 0.11 vs. 0.18 +/- 0.04 nmol/g, P < 0.001). Supplementation with vitamin E did not affect plasma 8-iso-PGF(sub 2 alpha) or 15-K-DH-PGF(sub 2 alpha) concentrations, liver total 8-iso-PGF(sub 2 alpha) or plasma malondialdehyde levels. Thus, vitamin E supplementation reduced urine basal levels of biomarkers of both nonenzymatic and enzymatic lipid peroxidation, in liver, vitamin E reduced the basal level of free 8-iso-PGF(sub 2 alpha) but not total 8-iso-PGF(sub 2 alpha).