Reproducibility of Dietary Biomarkers in a Multiethnic Asian Population.

SCOPE: Dietary biomarkers allow for study of diet and disease risk relationships, but a key requirement is that these biomarkers are reproducible and reflect long-term diet. This study assesses reproducibility of selected dietary biomarkers in a multi-ethnic Asian population, and quantifies diet-disease relationship attenuation arising from use of a single biomarker measurement. METHODS AND RESULTS: Intra-class correlation coefficients (ICC) are used to evaluate the reproducibility of urinary isoflavone and enterolignan, total plasma fatty acid (FA), and serum carotenoid concentrations measured 4 months apart in adult Singapore residents (ethnic Chinese, n 59; Malay, n 46; Indian, n 56). Total carotenoid ICC is 0.75 (95% confidence interval (CI) 0.68, 0.81), ranging from 0.63 to 0.84 for individual carotenoids. FA ICC (median) is 0.74 (inter-quartile range 0.70-0.78). Total isoflavone ICC (95% CI) is 0.21 (0.06-0.35). Total enterolignan ICC is 0.42 (0.28, 0.54). Attenuation factors associated with a single time point measure ranged from 0.74 to 0.94 for carotenoids and FAs, and 0.42 to 0.70 for isoflavones and enterolignans. CONCLUSIONS: In a multi-ethnic Asian population, single measures of most serum carotenoids and plasma FAs likely represent habitual diet, whereas reproducibility of urinary isoflavones and enterolignans is moderate, possibly due to rapid excretion.

Reduced antioxidant defense and increased oxidative stress in spinal cord injured patients.

OBJECTIVE: To determine the plasma and urine levels of antioxidants and oxidative stress biomarkers in subjects with spinal cord injury (SCI) the first year after injury. DESIGN: Descriptive 1-year follow-up study. SETTING: Rehabilitation and research center. PARTICIPANTS: SCI subjects (n=37; age range, 18-70 y) consecutively enrolled within the first month after injury. A healthy, able-bodied control group (n=346) was also included. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Blood and urine levels of antioxidants and oxidative stress biomarkers were measured at inclusion and after 3 and 12 months postinjury. RESULTS: One month after injury, the plasma antioxidants (total and oxidized glutathione and 6 different carotenoids and α-tocopherol) were reduced by 19% to 71% among the SCI subjects compared with the controls. The redox potential was reduced by 7% among the SCI subjects. The oxidative stress biomarker urinary 8-epi prostagladin F2α (PGF2α) increased to 161% in the SCI subjects compared with the controls. After 3 and 12 months, most of the antioxidant biomarkers were still significantly reduced compared with the controls, while urinary 8-epi PGF2α had increased to 208% compared with the controls. CONCLUSIONS: The levels of antioxidants were significantly lower, while the marker of oxidative stress was higher in the SCI subjects compared with the controls. This observation demonstrates that SCI patients experience increased oxidative stress and reduced antioxidant defense the first year after injury. Our findings warrant intervention studies where SCI patients receive dietary antioxidant support as part of their rehabilitation.

The biodistribution of a single oral dose of [14C]-lycopene in rats prefed either a control or lycopene-enriched diet.

Lycopene (lyc) has emerged as a primary candidate for dietary interventions of prostate cancer; however, research regarding its absorption, tissue distribution, and metabolism is limited. Previously, we evaluated the biodistribution (3-168 h) of a single oral dose of 14C-lyc in rats prefed lyc for 30 d. The liver was the primary depot for lyc, and the 14C and 14C-polar products appeared in tissues as early as 3 h after dosing. In the current study, F344 rats (n = 48) were randomly assigned to 1 of 4 groups prefed either a control or lyc-enriched diet (0.25 g lyc/kg diet) for 30 d and killed at 5 or 24 h after receiving a single oral dose of 14C-lyc. The percentage of the 14C dose absorbed at 24 h was lower (5.5 +/- 0.5%) in lyc-prefed (LP) rats than in control-prefed (CP) rats (6.9 +/- 0.4%, P < 0.04). Hepatic total 14C and 14C-lyc in CP rats was greater than in LP rats at 24 h (P < 0.005). A portion of 14C was delivered to extrahepatic tissues as early as 5 h, irrespective of diet. Of the tissues analyzed, an increase in the percentage in 14C-polar products occurred between 5 and 24 h only in the prostate and seminal vesicles, suggesting increased accumulation of 14C-polar products in these tissues, irrespective of prior dietary treatment. These data suggest that lyc absorption, tissue uptake, and catabolism were affected by prefeeding and that lyc can be partially taken up by extrahepatic tissues from the postprandial triglyceride-rich fraction.

[14C]-lycopene and [14C]-labeled polar products are differentially distributed in tissues of F344 rats prefed lycopene.

Epidemiologic evidence suggests a possible role for lycopene-rich foods in the prevention of prostate cancer and cardiovascular disease. Despite active research in disease reduction, there is a paucity of information on the absorption, biodistribution and metabolism of lycopene. The aim of this study was to evaluate the biodistribution of 14C-lycopene (specific activity, 1.83 microCi/mg) and 14C-labeled products after an oral dose of 22 microCi of 14C-lycopene in male rats that had been prefed a lycopene-containing diet (0.25 g lycopene/ kg diet) for 30 d. The percentage of 14C excreted in feces and urine over the 168 h was 68%. Quantitatively, serum 14C levels were maintained between 3 and 24 h then decreased at 72 h (P < 0.05). At all time points the majority of tissue 14C was in the liver (approximately 72%), although total hepatic 14C decreased after 24 h. In a comparison of the extrahepatic tissue at 168 h, the 14C was greatest in adipose tissue followed by spleen and then adrenal; approximately 80% of the 14C in the liver was in the cis and all-trans configuration at all time points. At 3 h, the 14C in seminal vesicles was primarily in the all-trans plus 5-cis forms (70%), but by 168 h, 55% of 14C was present as 14C-polar products. Despite the presence of unlabeled lycopene in the prostate, the primary 14C form was in 14C-polar products (67-92%), even at 3 h. The percentage and amount of 14C-polar products in the dorsolateral prostate lobe increased from 3 to 24 h and then reached a plateau. The data suggest that lycopene may be metabolized differently among tissues in rats prefed lycopene.

Chromatographic techniques for the determination of putative dietary anticancer compounds in biological fluids.

Although a great number of papers demonstrate an association between high intake of fruits and vegetables and reduced risk of certain types of cancer, the epidemiological evidence is not conclusive. The identification and quantification of specific dietary anticancer compounds in plasma, urine and tissues is an important aspect of this research. We surveyed the recent literature for original papers which involved the use of separation techniques for the detection and quantification in biological fluids and tissues of putative anticancer compounds which are present in the diet. The compounds included in this review are flavonoids, phytoestrogens, carotenoids, retinoids, vitamin E and ascorbic acid. The review covers papers published in the last 3 years. For each class of compounds we discuss the sample preparation, chromatographic conditions, and validation of the methods used, in order to identify current trends in the bioanalysis of each class of these substances.

Beta carotene uptake into atherosclerotic plaque: enhanced staining and preferential ablation with the pulsed dye laser.

The yellow color of atherosclerotic plaque is due to the presence of carotenoids, which absorb light between 430-530 nm and account for the preferential ablation of plaque by the pulsed dye laser operating at 480 nm. This study was designed to examine tissue uptake of beta-carotene and the effect of uptake on arterial plaque ablation. Forty-two atherosclerotic NZW rabbits were given intravenous beta-carotene at a dose of 40 mg/kg, twice weekly and killed between 1 hour and 28 days after the initial injection. beta-carotene was not detected in control specimens but was significantly greater in plaque than in normal wall at all time points following beta-carotene injection (P < 0.04 Mann Whitney U test). The ablation threshold was significantly lower in beta-carotene treated plaque than in untreated plaque or normal arterial wall (P < 0.01, Fisher's exact test). In this model beta-carotene is preferentially taken up into arterial plaque, resulting in increased absorption of laser radiation at 480 nm and enhanced tissue ablation.

Metabolic studies on retinoic acid in the rat.

The nature of metabolites in the urine arising from differentially labelled retinoic acid was investigated after injection of physiological doses into retinol-deficient rats. Distribution of radioactivity after partition of urine into ether-soluble, acidic and water-soluble fractions revealed that there were at least six metabolites in urine. Of these, the major metabolite(s) was one lacking both C-14 and C-15 of retinoic acid. Enzymic or alkaline hydrolysis of acidic and water-soluble fractions did not release any retinoic acid, thus indicating that retinoyl beta-glucuronide was not present in urine in significant amounts.