Jonathan E. Brown

In vivo bioavailability, absorption, excretion, and pharmacokinetics of [14C]procyanidin B2 in male rats.

Procyanidins are important biologically active compounds, but the pathway and extent of absorption and metabolism are controversial. We conducted a mass balance study to evaluate the total radioactivity excreted in urine and feces after oral administration of [14C]procyanidin B2 to male rats (n = 5). Urine and feces were collected daily from 0 to 96 h. Absolute bioavailability of 14C from [14C]procyanidin B2 was calculated as ∼82% using the values for total urinary 14C. A pharmacokinetic study measured total radioactivity in the blood (n = 9). Blood samples were collected at designated time intervals (0.5–24 h) after administration. Three treatments were used: 1) intravenous, 2) oral higher dose (21 mg/kg b.wt.), and 3) oral lower dose (10.5 mg/kg). Blood concentration of total 14C reached a maximum at ∼6 h after ingestion of [14C]procyanidin B2 (groups II and III), and area under the curve (AUC) was dependent on oral dose. After intravenous or oral administration the terminal half-lives were similar, whereas 8-fold larger values were obtained after oral dosing for total clearance and the apparent volumes of distribution. These pharmacokinetic differences explain the apparently lower 14C bioavailability (8–11%) for [14C]procyanidin calculated from blood [AUC(0–24)] values. After oral administration of [14C]procyanidin B2, 63% was excreted via urine within 4 days. The data suggest that much of the parent compound administered orally is degraded by the gut microflora before absorption and that these microbial metabolites have a different distribution from the compounds circulating after the intravenous dose.

Gliclazide: a general free radical scavenger

Free radical mechanisms have been implicated in diabetic microangiopathy. Agents that scavenge free radicals may be beneficial. We assessed the scavenging ability of two sulphonylureas, gliclazide and glibenclamide, in vitro. The assay which employs o-dianisidine sensitised by riboflavin can be used to distinguish between superoxide scavengers and general scavengers. The former species lead to an augmentation while the latter has an inhibitory effect. The drugs were added in final concentrations of 0.5, 1.0, 2.5 and 5.0 micrograms/ml. The percentage inhibition (mean +/- S.D.) for each concentration of gliclazide respectively was 11.0 +/- 2.5%, 20.8 +/- 2.9%, 31.4 +/- 2.2% and 47.2 +/- 0.8%. Glibenclamide had no scavenging effects. The results demonstrate that gliclazide is a powerful general free radical scavenger in vitro. We postulate that this scavenging quality of gliclazide may be important in diabetes.

Urinary isoflavone kinetics: the effect of age, gender, food matrix and chemical composition

Urinary isoflavone excretion is used to monitor compliance and examine biological effects. The present study determined if there were alterations in urinary isoflavone excretion following the ingestion of different soya foods and if age and gender potentially modified profiles. Twenty premenopausal women, seventeen post-menopausal women and twenty men received a defined single oral bolus dose (0.44 mg isoflavones/kg body weight) of soya milk, textured vegetable protein (TVP) or tempeh on three separate occasions. Baseline and four consecutive complete 24 h pooled urines were collected during each period. Urinary genistein recovery was influenced by gender and food matrix. For women the urinary genistein recovery was higher following soya-milk consumption compared with TVP (P<0.05). Tempeh consumption also resulted in an increased urinary genistein recovery relative to soya milk in premenopausal women (P<0.052). No differences in urinary genistein recoveries between soya foods were observed in the men. Although urinary daidzein excretion was similar across the foods studied and was not affected by age or gender, conversion to its intestinal metabolite, equol, resulted in potential matrix and chemical composition effects; urinary equol excretion was higher (P<0.01) following tempeh ingestion among equol producers. Together these data suggest that the fractional absorption of genistein is potentially different in men and women and is influenced by the food matrix and chemical composition. Furthermore, the data suggest that the metabolism of daidzein may be altered by the chemical composition of the isoflavones ingested. Further studies are required to examine the effect of higher intake and define the relative influence of these factors in elderly population groups.

Effect of fish-oil and vitamin E supplementation on lipid peroxidation and whole-blood aggregation in man

Free-living, healthy young men aged 21-35 years were divided into two groups, each group received dietary supplements of 15 g/day of fish-oil in the form of MaxEPA capsules, with or without an extra 400 I.U. of vitamin E, for two periods of four weeks. Blood samples were taken from an antecubital vein at two-week intervals. Plasma thiobarbituric acid reactive substances, conjugated dienes, vitamin E, creatine kinase, glucose and serum cholesterol were determined. Whole blood aggregation in response to collagen was determined by an electrical impedance method. Fish oil supplementation increased plasma thiobarbituric acid reactive substances after two weeks in vitamin E supplemented and non-supplemented groups but values returned to normal after four weeks in both groups regardless of the type of supplement given. No comparable increase in plasma conjugated dienes, creatine kinase or serum cholesterol was observed, the latter did not change significantly with diet. Plasma glucose increased when fish oil was supplemented, but only in the absence and not in the presence, of vitamin E supplementation. Whole blood aggregation decreased with the dietary fish oil in the presence, but increased in the absence, of vitamin E supplementation. These findings indicate an increased requirement for dietary antioxidant with high intakes of fish oil concentrates in man.

Estimates of daily net endogenous acid production in the elderly UK population : analysis of the National Diet and Nutrition Survey (NDNS) of British adults aged 65 years and over

Dietary intake has been shown to influence acid-base balance in human subjects under tightly controlled conditions. However, the net effect of food groups on alkali/acid loading in population groups is unclear. The aims of the present study were to: (1) quantify estimates of daily net endogenous acid production (NEAP) (mEq/d) in a representative group of British elderly aged 65 years and older; (2) compare and characterise NEAP by specific nutrients and food groups likely to influence dietary acid loading; (3) determine whether geographical location influenced NEAP. The National Diet and Nutrition Survey dataset, consisting of a 4 d weighed record and anthropometric data, was used to estimate dietary acidity. Dietary under-reporters were excluded by analysing only subjects with energy intakes >/= 1.2 x BMR. NEAP was estimated as the dietary potential renal acid load+organic acid excretion, the latter as a multiple of estimated body surface area. NEAP was lower in women compared with men (P < 0.001), and lower than values reported in a Swedish elderly cohort. Lower dietary acidity was significantly associated with higher consumption of fruit and potatoes and lower consumption of meat, bread and eggs (P < 0.02 to P < 0.001). Lower intakes of fish and cheese were associated with lower NEAP in men only (P < 0.01 to P < 0.001). There were regional differences for NEAP, with higher intakes in Scotland/Northern regions compared with Central/South-Western and London/South-Eastern regions (P = 0.01). These data provide an insight into the acid-generating potential of the diet in the British elderly population, which may have important consequences in this vulnerable group.

A study of Hassawi rice ( Oryza sativa L.) in terms of its carbohydrate hydrolysis ( in vitro ) and glycaemic and insulinaemic indices ( in vivo )

Background/Objectives:A high prevalence of Type 2 diabetes exists in Saudi Arabia. Epidemiological evidence suggests that low glycaemic index (GI) diets reduce diabetes risk. Yet, little is known about the GI of traditional Saudi Arabian staples such as Hassawi rice (HR). HR was evaluated in terms of its GI and insulinaemic index (II). Comparisons were made in vitro assessing glucose released enzymatically. A long-grain rice variety available in both United Kingdom and Saudi Arabia was studied as a comparison.Subjects/Methods:For GI and II measurements, HR, Uncle Bens rice (UBR) and a standard glucose solution were consumed by healthy subjects (n=13) on seven randomised occasions. Capillary bloods were collected at specific times over 2 h after food intake. Food and Agriculture Organization/World Health Organization protocols were used to determine GI and II. For the in vitro studies, cooked rice was incubated with hydrolytic enzymes under standardised conditions. Samples were taken at t=20 and t=120 min and rapidly available glucose (RAG) and slowly available glucose (SAG) were computed.Results:Values of RAG and SAG were lower for HR compared with their respective values for UBR (P<0.001 and P=0.011, respectively). However, no significant difference was observed for GI (P>0.05) despite a lower insulin response noted for HR (P=0.007).Conclusions:HR had a similar GI to UBR, although a lower insulin response was evident. RAG and SAG values were different for the two rice varieties despite similar GI values. These differences may be important in terms of their metabolic impact and outcome on diabetes.

Effects of processing on the polyphenol and phenolic acid content and antioxidant capacity of semi-dried cherry tomatoes (Lycopersicon esculentum M.).

BACKGROUND This study was performed to test the effects of pre-treating cherry tomatoes with a solution containing citric acid-NaCl-CaCl2 (10:10:24 g L(-1)), followed by one of three different drying regimes (40, 60, 80 °C) on the antioxidant capacity of their aqueous extracts and the extent of phenolic compound degradation. RESULTS Chlorogenic acids, caffeic acid, ferulic acid, rutin and naringenin were all detected in the aqueous extracts. In fresh cherry tomatoes the predominant phenolic compound was rutin, followed by naringenin, which corresponded to 79% and 8% of the total phenolic compounds present, respectively. Pre-treatment was protective towards naringenin and had a modest protective effect on rutin and ferulic acid (0.1 > P > 0.05). Total phenolic content was similar in all samples, but there was a trend for the level of free polyphenols to be lower in treated tomatoes. The destruction of naringenin was confirmed by liquid chromatographic-mass spectrometric data. CONCLUSION A significant effect of temperature on the antioxidant capacity was observed. After this treatment the industry might introduce some advances in the processing of tomatoes, preserving the main nutritive characteristics and saving the products as semi-dried.

Development of a food compositional database for the estimation of dietary intake of phyto-oestrogens in a group of postmenopausal women previously treated for breast cancer and validation with urinary excretion

The scientific literature contains evidence suggesting that women who have been treated for breast cancer may, as a result of their diagnosis, increase their phyto-oestrogen (PE) intake. In the present paper, we describe the creation of a dietary analysis database (based on Dietplan6) for the determination of dietary intakes of specific PE (daidzein, genistein, glycitein, formononetin, biochanin A, coumestrol, matairesinol and secoisolariciresinol), in a group of women previously diagnosed and treated for postmenopausal breast cancer. The design of the database, data evaluation criteria, literature data entry for 551 foods and primary analysis by LC–MS/MS of an additional thirty-four foods for which there were no published data are described. The dietary intake of 316 women previously treated for postmenopausal breast cancer informed the identification of potential food and beverage sources of PE and the bespoke dietary analysis database was created to, ultimately, quantify their PE intake. In order that PE exposure could be comprehensively described, fifty-four of the 316 subjects completed a 24 h urine collection, and their urinary excretion results allowed for the description of exposure to include those identified as ‘equol producers’.

Effect of reserpine treatment on low-density lipoproteins in arterial wall and internal organs of rats.

The effects were determined in rats of single injections of reserpine at increasing doses (0.5, 1.58, and 5.0 mg/kg) on low-density lipoprotein (LDL) and cholesterol in aortic wall, heart, liver, kidney, and adrenal gland. Catecholamine levels in plasma, heart, and liver, arterial blood pressure, and heart rate were also monitored. Reserpine was injected intraperitoneally, followed immediately by the administration of [3H]cholesterol by gavage. Twelve hours later, homologous 125I-tyramine cellobiose-labeled LDL (125I-TC-LDL) was injected intravenously. Twenty-four hours later, the rats were killed, and the radioactivities of aortic walls, heart, liver, kidney, and adrenal glands were determined. The results showed that after reserpine treatment the accumulation of both the 125I-TC label derived from LDL and total [3H]cholesterol was significantly reduced in aortic wall and heart, increased in liver, and unchanged in the kidney and adrenal gland. At higher doses (1.58 and 5.0 mg/kg), reserpine significantly accelerated the plasma clearance of radiolabelled LDL. Plasma noradrenaline in reserpine-treated animals decreased maximally (86%) by 12 h and by 61-71% at 36 h compared with the control. Plasma adrenaline increased transiently after injection of reserpine and then returned to the basal levels. Reserpine greatly decreased noradrenaline and adrenaline levels in heart and liver. Arterial blood pressure was decreased significantly (0.001 < p < 0.05) at 12 h by the two lower doses of reserpine and then returned to normal values over the next 24 h. The results indicate that reserpine decreases LDL cholesterol in artery wall and heart and increases it in liver. These findings suggest that reserpine could find a new use as a cholesterol-lowering drug for the prevention of atherosclerosis.

Food choice and phytoestrogen consumption in women previously treated for postmenopausal breast cancer

Background Phytoestrogens are plant-derived, bioactive substances with a chemical structure similar to that of 17-oestradiol. Women previously treated for breast cancer may increase their phytoestrogen intake to avoid conventional hormone replacement therapy or because of a belief that they may help avoid recurrence [1,2]. There is no recommended daily intake and there are some concerns about phytoestrogen safety in this group, although the evidence is conflicting and more research is needed [3,4]. Methods Three hundred and sixteen women each completed a 4- day food and drink diary (14 of whom also completed a 7-day weighed intake diary 6 weeks previously). The 55 most recently recruited women collected their urine for 24 hours whilst completing their diaries and were interviewed by telephone regarding their food choices since diagnosis. Results A new dietary analysis database was created using peerreviewed published data and analysing 34 additional foods and beverages for which there were no published results. The urinanalysis results contributed validation data. A summary of the dietary intake data is shown in Table 1. There was a lack of primary analytical data on the phytoestrogen profile of many foods and beverages routinely consumed by this study population. However, food frequency data from the highest quartile show the important contribution of nonsoya foods to high intakes (Table 2). Telephone interviews were completed by 39 subjects. For most women, having breast cancer had not changed their diet. Health concerns unrelated to cancer, the needs of other family members, cooking on a budget and physical appearance all seemed more important than the impact of the cancer diagnosis. Discussion Variation in phytoestrogen intakes and metabolite excretion reflect food preferences, dietary analysis database limitations and likely variations in existing knowledge combined with a lack of routine access to dietary information. In the absence of definitive advice, more immediate health and social concerns influence food choice rather than past breast cancer diagnosis. Conclusion No data previously existed on intake in this potentially vulnerable group and these data will help evaluate the health implications related to such phytoestrogen consumption patterns. Acknowledgement Funded by the Food Standards Agency, UK. References 1. Adlercreutz H: Phytoestrogens and breast cancer. J Steroid Biochem Mol Biol 2002, 83:113-118. 2. Mills E, Ernst E, et al.: Health food store recommendations:implications for breast cancer patients. Breast Cancer Res 2003, 5:170-174. 3. De Lemos M: Safety issues of soy phytoestrogens in breast cancer patients. J Clin Oncol 2002, 20:3040-3041. 4. Committee on Toxicology of Chemicals in Food, Consumer Products and the Environment. Phytoestrogens and Health. London: Food Standards Agency; 2003.