Flavonoids in human urine as biomarkers for intake of fruits and vegetables.

Flavonoids are polyphenolic compounds ubiquitously found in human diets. We have studied the association between urinary excretion of flavonoids and the intake of fruits and vegetables to evaluate the usefulness of flavonoids as a biomarker for fruit and vegetable intake. Levels of 12 dietary relevant flavonoids were determined by LC-MS in urine samples collected prior to an intervention study, when the subjects were on their habitual diet (n = 94), and after they had participated in an intervention study with diets either high or low in fruits, berries, and vegetables (n = 77). Both flavonoid glycosides and aglycones were included in the assay, but only the flavonoid aglycones were detectable. Thus, the flavonols quercetin, kaempferol, isorhamnetin, and tamarixetin, the dihydrochalcone phloretin, and the flavanones naringenin and hesperetin were quantified in the enzymatically hydrolyzed urine samples. The habitual intake of fruits and vegetables, determined by 3-day dietary records before the intervention study, correlated significantly with the total excretion of urinary flavonoids, with a coefficient of correlation of 0.35, P < 0.005 (n = 94). In addition, highly significant differences in the urinary excretion of all flavonoids were observed in the human intervention study between subjects on diets high or low in fruits, berries, and vegetables. Also, at the individual level a significant positive correlation between changes in fruit and vegetable intake and changes in urinary flavonoid excretion was observed. We conclude that urinary flavonoids may be useful as a new biomarker for fruit, berry, and vegetable intakes and may prove useful when the possible health protective effects of flavonoids are studied.     

Determination of DNA adducts of malonaldehyde in humans: effects of dietary fatty acid composition

The effects of dietary fatty acid composition on the endogenousformation of DNA adducts of malonal-dehyde (MA), the major productof lipid peroxidation, were investigated in humans. A groupof 59 healthy individuals of both sexes and different ages wasinitially fed a milk fat-based diet rich in saturated fattyacids for 14 days. Following this initial period, after whichthe group was considered homogeneous with respect to diet, 30randomly chosen subjects were given a sunflower oil-based (richin polyunsaturated fatty acids) (SO) diet and the remaining29 individuals a low erucic acid rapeseed oil-based (rich inmonounsaturated fatty acids) (RO) diet for 25 days. The fattyacid composition of plasma lipid fractions and the level ofDNA adducts of MA in total white blood cells were then determinedat the end of the SO and RO dietary periods. DNA adduct levelswere measured by ³²P-post-labelling using reversed-phase HPLCwith on-line detection of radioactivity. Higher concentrationsof polyunsaturated fatty acids in plasma triglycerides and higherlevels of DNA adducts of MA were found in the subjects on theSO diet when compared with those in the RO dietary group. Alarge inter-individual variation in adduct levels was observed.The average adduct level in the SO diet group was 7.4 ±8.7 adducts/10⁷ nucleotides (n = 23). This level was 3.6-foldhigher than that found in individuals in the RO diet group (P< 0.001). Our results, in conjunction with the mutagenicand carcinogenic properties of MA, thus suggest the interactionof lipid peroxidation products such as MA with DNA as one pausiblemechanism explaining the involvement of dietary fat in carcinogenesis.     

Parenteral Plant Sterols Accumulate in the Liver Reflecting Their Increased Serum Levels and Portal Inflammation in Children With Intestinal Failure

Background: Parenteral plant sterols (PSs) are considered hepatotoxic; however, liver PSs and their associations with liver injury in patients with intestinal failure (IF) have not been reported. Materials and Methods: We analyzed liver and serum PS (avenasterol, campesterol, sitosterol, and stigmasterol) concentrations and ratios to cholesterol and their associations with biochemical and histologic liver damage in children with IF during (n = 7) parenteral nutrition (PN) and after weaning off it (n = 9), including vegetable oil–based lipid emulsions. Results: Liver avenasterol, sitosterol, and total PS concentrations and cholesterol ratios were 2.4‐fold to 5.6‐fold higher in PN‐dependent patients (P < .05). Parenteral PS delivery reflected liver avenasterol and sitosterol ratios to cholesterol (r = 0.83–0.89, P = .02–.04), while serum and liver total PS levels were positively interrelated (r = 0.98, P < .01). Any liver histopathology was equally common while portal inflammation more frequent (57 vs 0%, P = .02) in PN‐dependent patients. All liver PS fractions correlated positively with histologic portal inflammation (r = 0.53–0.66, P < .05), and their total concentration was significantly (P = .01) higher among patients with versus without portal inflammation. In PN‐dependent patients, liver fibrosis and any histopathology correlated with liver campesterol and stigmasterol levels (r = 0.79–0.87, P ≤ .03). Conclusion: Among children with IF, parenteral PSs accumulate in the liver, reflect their increased serum levels, and relate with biochemical liver injury, portal inflammation, and liver fibrosis, thus supporting their role in promoting liver damage.     

Berries as chemopreventive dietary constituents--a mechanistic approach with the ApcMin/+ mouse

Berries contain a number of compounds that are proposed to have anticarcinogenic properties. We wanted to see if pure ellagic acid, natural ellagitannins and three wild berries have any effect on the adenoma formation in Apc- mutated Min/+ mice. Min/+ mice were fed high-fat AIN93-G diets containing 10% (w/w) freeze-dried bilberry (Vaccinium myrtillus), lingonberry (Vaccinium vitis-idaea), cloudberry (Rubus chamaemorus), cloudberry seeds or cloudberry pulp or pure ellagic acid at 1564 mg/kg for 10 weeks. beta-Catenin and cyclin D1 protein levels in the adenomas and in the normal-appearing mucosa were determined by Western blotting and immunohistochemistry. Early changes in gene expression in the normal-appearing mucosa were analyzed by Affymetrix microarrays. Three wild berries significantly reduced tumour number (15-30%, p < 0.05), and cloudberry and lingonberry also reduced tumour size by over 60% (p < 0.01). Cloudberry resulted in decreased levels of nuclear beta-catenin and cyclin D1 and lingonberry in the level of cyclin D1 in the large adenomas (p < 0.05). Affymetrix microarrays revealed changes in genes implicated in colon carcinogenesis, including the decreased expression of the adenosine deaminase, ecto-5f-nucleotidase and PGE2 receptor subtype EP4. Ellagic acid had no effect on the number or size of adenomas in the distal or total small intestine but it increased adenoma size in the duodenum when compared with the control diet (p < 0.05). Neither cloudberry seed nor pulp had any effect on the adenoma formation. Berries seem to have great potential as a source of chemopreventive components.     

Three Nordic berries inhibit intestinal tumorigenesis in multiple intestinal neoplasia/+ mice by modulating beta-catenin signaling in the tumor and transcription in the mucosa

Berries contain a number of compounds that are proposed to have anticarcinogenic properties. We studied the effects and molecular mechanisms of wild berries with different phenolic profiles on intestinal tumorigenesis in multiple intestinal neoplasia/+ mice. The mice were fed a high-fat AIN93-G diet (Con) or AIN93-G diets containing 10% (w:w) freeze-dried bilberry, lingonberry (LB), or cloudberry (CB) for 10 wk. All 3 berries significantly inhibited the formation of intestinal adenomas as indicated by a 15-30% reduction in tumor number (P < 0.05). CB and LB also reduced tumor burden by over 60% (P < 0.05). Compared to Con, CB and LB resulted in a larger (P < 0.05) proportion of small adenomas (43, 69, and 64%, respectively) and a smaller proportion of large adenomas (56, 29, and 33%, respectively). Beta-catenin and cyclin D1 in the small and large adenomas and in the normal-appearing mucosa were measured by Western blotting and immunohistochemistry. CB resulted in decreased levels of nuclear beta-catenin and cyclin D1 and LB in the level of cyclin D1 in the large adenomas (P < 0.05). Early changes in gene expression in the normal-appearing mucosa were analyzed by Affymetrix microarrays, which revealed changes in genes implicated in colon carcinogenesis, including the decreased expression of the adenosine deaminase, ecto-5'-nucleotidase, and prostaglandin E2 receptor subtype EP4. Our results indicate that berries are potentially a rich source of chemopreventive components.     

Effects of cumulative sleep restriction on self‐perceptions while multitasking

This study addressed a rarely studied question of self‐perceptions of performance and overall functional state during cumulative sleep restriction and the ensuing recovery period. Twenty healthy male volunteers, aged 19–29 years, were divided into a sleep restriction group (n = 13) and a control group (n = 7). On the first 2 nights, the sleep restriction group had an 8‐h sleep opportunity that was restricted to 4 h for the next 5 nights, and then restored to 8 h for the last 2 nights. The control group had an 8‐h sleep opportunity each night. Each day participants accomplished 50‐min multitask sessions and gave self‐ratings in their connection. Similar to our previous findings on multitasking performance, self‐perceived task performance, sleepiness and mental fatigue impaired during the sleep restriction and returned to baseline during the recovery phase. Self‐perceived mental effort, tension, task difficulty and task pace showed no sensitivity to the sleep restriction. We concluded that sleep‐restricted individuals can probably make use of some self‐perceptions when assessing their ‘fitness for duty’. However, at the individual level these measures seem to be inaccurate in revealing actual performance impairments.     

Work and personal resources as long‐term predictors of well‐being

The aim of this longitudinal study was to recognize the work and personal factors that predict well‐being in the long run. The empirical analyses are based on sample data from a larger survey in 1986 and from the 10‐year follow‐up. Well‐being was determined in terms of psychological and physiological symptoms of strain. Discriminant analysis was used to identify the predictor variables which best characterize the differences between the extreme strain groups. Differences were observed in the strength of work and personal resources between workers with low and high strain, and in the role of these resources in the process of staying well at work. Strong personal resources, especially strong sense of coherence, seem to protect workers from strain and thus maintain well‐being. At work, factors related to social processes, i.e. social support and appreciation from colleagues and superiors, act as primary work‐related resources. In general, the personal resources were better discriminating factors than the work characteristics. Well‐being was found to be relatively stable. Copyright © 2002 John Wiley & Sons, Ltd.