Hydration biomarkers in free-living adults with different levels of habitual fluid consumption.

Little is known about the impact of habitual fluid intake on physiology. Specifically, biomarkers of hydration status and body water regulation have not been adequately explored in adults who consume different fluid volumes in everyday conditions, without prolonged exercise or environmental exposure. The purpose of the present study was to compare adults with habitually different fluid intakes with respect to biomarkers implicated in the assessment of hydration status, the regulation of total body water and the risk of kidney pathologies. In the present cross-sectional study, seventy-one adults (thirty-two men, thirty-nine women, age 25­40 years) were classified according to daily fluid intake: thirty-nine low drinkers (LD; ≤ 1·2 litres/d) and thirty-two high drinkers (HD; 2­4 litres/d). During four consecutive days, urinary parameters (first morning urine (FMU) on day 1 and subsequent 24 h urine (24hU) collections), blood parameters, and food and beverage intake were assessed. ANOVA and non-parametric comparisons revealed significant differences between the LD and HD groups in 24hU volume (1·0 (se 0·1) v. 2·4 (se 0·1) litres), specific gravity (median 1·023 v. 1·010), osmolality (767 (se 27) v. 371 (se 33) mOsm/kg) and colour (3·1 (se 0·2) v. 1·8 (se 0·2)). Similarly, in the FMU, the LD group produced a smaller amount of more concentrated urine. Plasma cortisol, creatinine and arginine vasopressin concentrations were significantly higher among the LD. Plasma osmolality was similar between the groups, suggesting physiological adaptations to preserve plasma osmolality despite low fluid intake. The long-term impact of adaptations to preserve plasma osmolality must be examined, particularly in the context of renal health.

Bioavailability of glycitein relatively to other soy isoflavones in healthy young Caucasian men.

Glycitein is a Selective Estradiol Receptor Modulator (SERM) from soy. The study reports plasma bioavailability and urine excretion of glycitein compared to other soy isoflavones after a unique intake of food supplement based on soy germ containing 55.24mg isoflavones. Eighteen plasma and urinary sampling profiles collected over 48h from healthy young Caucasian men were analysed using specific ELISAs. Eight profiles contained equol. Glycitein T(max), C(max), AUC(0→24h) and T(½) in plasma were calculated. Urine T(max), % of excretion at 24h and clearance were assessed. Glycitein is one of the best absorbed flavonoids. Plasma steady-state level can be achieved by several intakes a day. Glycitein bioavailability is similar to that of daidzein and its urinary excretion is significantly higher than that of genistein. Equol does not affect glycitein bioavailability. Knowing glycitein bioavailability in man is essential for the development of soy-germ-based food supplements for health applications.

Pharmacokinetic analysis of absorption, distribution and disappearance of ingested water labeled with D2O in humans.

The kinetic parameters of absorption and distribution of ingested water (300 ml labeled with D(2)O; osmolality <20 mOsm kg(-1)) in the body water pool (BWP) and of its disappearance from this pool were estimated in 36 subjects from changes in plasma or urine deuterium to protium ratio (D/H) over 10 days using one- and two-compartment and a non-compartmental pharmacokinetic models (1-CM, 2-CM and N-CM which applied well to 58, 42 and 100% of the subjects, respectively). Compared with the volume and turnover of the BWP computed with the slope-intercept method (60.7 ± 4.1% body mass or 72.7 ± 3.2% lean body mass; turnover 4.58 ± 0.80 l day(-1): i.e., complete renewal in ~50 days; n = 36), the values were accurately estimated with the N-CM and 1-CM and were slightly overestimated and underestimated, respectively, with the 2-CM (~7-8% difference, significant for water clearance only). Ingested water appeared in plasma and blood cells within 5 min and the half-life of absorption (~11-13 min) indicates a complete absorption within ~75-120 min. The 2-CM showed that in 42% of the subjects, ingested water quickly distributed within a central compartment before diffusing with a very short half-life (12.5 ± 4.3 min) to a peripheral compartment (18.5 ± 4.3 and 31.6 ± 6.4 L, respectively), which were in complete equilibrium within ~90 min. Pharmacokinetic analyses of water labeled with D(2)O can help describe water absorption and distribution, for which there is no well defined reference method and value; depending on the characteristics of the subjects and the drinks, and of environmental conditions.

Hydration-sensitive gene expression in brain.

Dehydration has a profound influence on neuroexcitability. The mechanisms remained, however, incompletely understood. The present study addressed the effect of water deprivation on gene expression in the brain. To this end, animals were exposed to a 24 hours deprivation of drinking water and neuronal gene expression was determined by microarray technology with subsequent confirmation by RT-PCR. As a result, water deprivation was followed by significant upregulation of clathrin (light polypeptide Lcb), serum/glucocorticoid-regulated kinase (SGK) 1, and protein kinase A (PRKA) anchor protein 8-like. Water deprivation led to downregulation of janus kinase and microtubule interacting protein 1, neuronal PAS domain protein 4, thrombomodulin, purinergic receptor P2Y - G-protein coupled 13 gene, gap junction protein beta 1, neurotrophin 3, hyaluronan and proteoglycan link protein 1, G protein-coupled receptor 19, CD93 antigen, forkhead box P1, suppressor of cytokine signaling 3, apelin, immunity-related GTPase family M, serine (or cysteine) peptidase inhibitor clade B member 1a, serine (or cysteine) peptidase inhibitor clade H member 1, glutathion peroxidase 8 (putative), discs large (Drosophila) homolog-associated protein 1, zinc finger and BTB domain containing 3, and H2A histone family member V. Western blotting revealed the downregulation of forkhead box P1, serine (or cysteine) peptidase inhibitor clade H member 1, and gap junction protein beta 1 protein abundance paralleling the respective alterations of transcript levels. In conclusion, water deprivation influences the transcription of a wide variety of genes in the brain, which may participate in the orchestration of brain responses to water deprivation.

Influence of ethnic origin (Asian v. Caucasian) and background diet on the bioavailability of dietary isoflavones.

Soya isoflavones: genistein and daidzein are increasingly consumed in Western countries. Their beneficial effects are discussed considering nutrition and health in Asia. The present study aimed to check whether chronic ingestions, ethnic origin and dietary context can influence soya phyto-oestrogen bioavailability. Two prospective trials were carried out to blindly assess the pharmacokinetics after acute and chronic intake of soya-based cheese (45.97 (sd1.57) mg isoflavones) taken once a day for 10 d. Twelve healthy young Asians immersed for 2 months in France were randomised in a cross-over design to compare the influence of a Western v. Asian dietary context. The second trial partly nested in the first one, compared Asians under the Western diet to twelve healthy young male Caucasians under the same diet. All volunteers were non-equol producers. After an acute intake of soya in Western diet, Asians exhibited higher maximum concentration measured in plasma (Cmax) and area under the plasma concentration-time curve (AUC) for genistein and daidzein than Caucasians (P = 0.005, 0.006, 0.032 and 0.008, respectively). In Caucasians under Western diet, AUC and Cmax values significantly increased after chronic intake. This was not the case for daidzein in Asians whatever the dietary context. For the first time, it is evidenced that on acute intake of soya cheese, Asians absorb soya phyto-oestrogens better than Caucasians, regardless of whether the background diet is Western or Asian. On chronic ingestions, AUC and Cmax values were increased for daidzein and genistein in Caucasians but not in Asians. There are ethnic differences in isoflavone pharmacokinetic and bioavailability. This may influence health outcomes.

Synthesis of haptens and conjugates for ELISA of glycitein: development and validation of an immunological test.

Two carboxylic acid haptens of glycitein were synthesized, with a spacer arm at the C2 position. They differed in the length of the spacer arm, with the length of the spacer arms being three or four carbon atoms, and were named Delta3-glycitein and Delta4-glycitein haptens, respectively. The different haptens were coupled to bovine serum albumin (BSA), and the coupling efficiency was assessed by MALDI mass spectrometry. Polyclonal antibodies were generated against the BSA conjugates. An additional conjugate of Delta4-glycitein hapten was generated with swine thyroglobulin (Thyr). Enzyme-linked immunosorbent assays (ELISAs) based on the competition between free glycitein and Delta4-glycitein-Thyr conjugates for specific antibodies were developed. The IC50 of the standard curves was 15.6 ng mL(-1) with anti-Delta3-glycitein and 62.5 ng mL(-1) with anti-Delta4-glycitein, that is, 10.9 and 44 pmol/well, respectively. With the Delta3-glycitein antibody, interassay and intra-assay variations were 12.2 and 11.5%, respectively. Specificity tests did not show any significant cross-reaction with any other soy isoflavone. This specificity is not influenced by the length of the spacer arm. The assay was validated by measurements performed on plasma samples as well as on soy-based foodstuffs and on soy-based food supplements.

Higher bioavailability of isoflavones after a single ingestion of a soya-based supplement than a soya-based food in young healthy males.

Soya isoflavones, genistein and daidzein, are the focus of numerous studies investigating their potential effects on health and results remain controversial. Bioavailability is clearly a crucial factor influencing their bioefficacy and could explain these discrepancies. This study aimed at assessing: (1) the isoflavone content of sixty-nine European soya-derivative products sold on the French market; (2) the bioavailability of isoflavones comparing supplement with food. Twelve healthy volunteers were recruited in a randomized two-way crossover trial and received 35 mg isoflavones equivalent aglycone either through supplements or through cheese, both containing different patterns of isoflavone conjugates and different daidzein:genistein ratios. A specific ELISA method was used to assess the plasma and urinary concentrations of isoflavones and thus the pharmacokinetic parameters, which were then normalized to mg of each isoflavone ingested. Results showed that the normalized Cmax of daidzein (P = 0.002) and similarly the normalized AUC0 --> infinity and Cmax of genistein (P = 0.002) from soya-based capsules were higher than that from soya-based cheese. In conclusion, this work completes studies on isoflavone bioavailability and presents new data regarding isoflavone concentrations in soya-derivative products. Assuming that isoflavone conjugation patterns do not influence isoflavone bioavailability, this study shows that isoflavones contained in capsules are more bioavailable than those contained in soya-based cheese. Although the supplement is more bioavailable, the relative importance of this is difficult to interpret as there is little evidence that supplements are biologically active in human subjects to date and further studies will be necessary for this specific supplement to prove its efficacy.

Bioavailability and urinary excretion of isoflavones in humans: effects of soy-based supplements formulation and equol production.

Soy isoflavones (IF) are of particular interest for their possible estrogenic effects on the symptoms of menopause. The bioavailability of IF is clearly a factor influencing their biological activity. The first aim of this study was to elucidate the impact of the matrix process and especially the formulation of soy-based capsules on IF bioavailability. Twelve healthy volunteers were recruited for a randomized, double-blind, two-way crossover trial and received a single dose of the two soy-based formulations, one containing a pure soy standardized extract of IF, and the other containing soy flour in addition to the standardized extract of IF. Using a new and validated ELISA method, we measured the plasma and urinary concentrations of genistein, daidzein and its metabolite equol. Based on European Medicine Evaluation Agency recommendations, the main pharmacokinetic parameters allowed us to demonstrate the bioequivalence of the two formulations, indicating that the presence or absence of soy flour did not alter either the absorption or the elimination of daidzein and genistein. As bioequivalence was demonstrated, we pooled data collected during the two study-periods to address another original issue: Did the ability to produce equol affect the bioavailability of daidzein? We demonstrated that daidzein excretion was significantly lower in equol producers compared with equol non producers over the entire elimination period of the soy IF. This difference disappeared when equol excretion was added to daidzein excretion in equol producers. Our results indicated that the production of equol could partly explain the difference in daidzein bioavailability after IF ingestion.