Sucrose as an added sweetener in diabetes mellitus

For many years the Diabetes Associations of several countries have recommended the dietary elimination of added sucrose. However, contrary to popular belief, there is no evidence that modest use of added sucrose is detrimental to diabetic control. In this study of 17 non-insulin dependent diabetics, the medium-term metabolic effects of the daily supplementation of a subject's usual diet with either 28 g of sucrose or with saccharin and starch of equivalent sweetener and energy value, were compared over six-week periods. Neither dietary period had any significant effect on fasting concentrations of blood glucose, plasma insulin, GIP or serum triglyceride. The metabolic responses to two different test meals, consisting of a standard breakfast supplemented with either sucrose or saccharin plus starch, did not differ significantly either between test meals or between dietary periods. Similarly neither dietary period had any significant effect on urinary excretion of glucose. Na+ or K+. There was no significant difference in mean blood pressure between dietary periods.

The results of this medium-term study indicate that there are no metabolic contraindications to including a moderate amount of sucrose (up to 28 g e 7 teaspoons) in the diets of patients with non-insulin dependent diabetes mellitus.

Sucrose and lollypops to reduce immunisation pain in toddlers and young children: two pilot randomised controlled trials

Aims To evaluate the feasibility, acceptability and preliminary efficacy of sweet taste in reducing pain in toddlers and pre-school children during immunisation and to use the results to inform a sample size estimation for future full-scale trials. Background Sweet solutions reduce procedural pain in newborn infants and in infants beyond the newborn period. It is unclear if sweet taste continues to reduce procedural pain in children older than one year of age. Design Two parallel design pilot randomised controlled trials (RCTs). Methods Children attending an Immunisation Drop-in Clinic at a children's hospital in Australia participated in one of two pilot RCTs: 1) a double-blinded RCT of 33% sucrose compared to water in toddlers receiving their 12- or 18-month immunisation or 2) a non-blinded RCT of lollypop compared to standard care (active distraction using bubble and pin wheel blowing) in pre-school children aged 3-5 years. Primary outcomes included cry incidence and duration and pain score using the FLACC. Results Interventions, standard care and all aspects of the study were acceptable to children, parents and immunisation nurses. More toddlers in the sucrose group received their 12-month immunisation and more injections (n=35) compared to toddlers randomised to water (n=26). There were no significant differences in crying time or pain scores between intervention and control groups in either pilot RCT. Conclusion The study interventions are acceptable to children and parents. Full-scale trials would be feasible to conduct. Implications for clinical practice Toddlers receiving their 12-month immunisation should be the focus of future full-scale RCTs.

Energy density of foods and beverages in the Australian food supply: influence of macronutrients and comparison to dietary intake

Objectives: The energy density (ED) of the diet is considered an important determinant of total energy intake and thus energy balance and weight change. We aimed to compare relationships between ED and macronutrient content in individual food and beverage items as well as population diet in a typical Western country. Design: Nutrient data for 3673 food items and 247 beverage items came from the Australian Food and Nutrient database (AusNut). Food and beverage intake data came from the 1995 Australian National Nutrition Survey (a 24-h dietary recall survey in 13 858 people over the age of 2). Relationships between ED and macronutrient and water content were analysed by linear regression with 95% prediction bands. Results: For both individual food items and population food intake, there was a positive relationship between ED and percent energy as fat and negative relationships between ED and percent energy as carbohydrate and percent water by weight. In all cases, there was close agreement between the slopes of the regression lines between food items and dietary intake. There were no clear relationships between ED and macronutrient content for beverage items. Carbohydrate (mostly sucrose) contributed 91, 47, and 25% of total energy for sugar-based, fat-based, and alcohol-based beverages respectively. Conclusions: The relationship between ED and fat content of foods holds true across both population diets and individual food items available in the food supply in a typical Western country such as Australia. As high-fat diets are associated with a high BMI, population measures with an overall aim of reducing the ED of diets may be effective in mediating the growing problem of overweight and obesity.

Rapid determination of carbohydrates in heroin drug seizures using capillary electrophoresis with short-end injection

A simple and rapid method for the analysis of carbohydrates in heroin samples by capillary electrophoresis utilizing a borate complexation method is described. Separations were performed using an uncoated fused silica capillary, 50 cm × 50 mm I.D. × 360 mm O.D. with an effective separation length of 9 cm. The system was run at 60°C with an applied voltage of -8 kilovolts. Injection of each sample was for 1 sec at -50 mbar. UV detection was employed with the wavelength set at 195 nm. The background electrolyte consisted of 65 mM borate, pH 12.0. Samples and standards were prepared in the run buffer containing 2 mg/mL of mannose as an internal standard. Under these conditions a test mixture containing glucose, sucrose, lactose, mannitol and mannose as an internal standard was resolved within 5 min. The method was used to determine the concentration of carbohydrates in heroin seizure samples and synthetic heroin samples. The results were in good agreement with the reported values.

Caffeine as a flavor additive in soft-drinks

Over 60% of soft-drinks sold in the United States contain caffeine, a mildly addictive psycho-active chemical, as a flavor additive. Using sweeteners as controls, we assessed whether caffeine has flavor activity in a cola soft-drink. A forced-choice triangle discrimination methodology was used to determine detection thresholds of caffeine in sweeteners and a cola beverage. The subjects (n=30, 28 female, 23±4 years old) were trained tasters and completed over 1600 discrimination tests during the study. The mean detection thresholds for caffeine in the sweet solutions were: 0.333±0.1 mM sucrose; 0.467±0.29 mM aspartame; 0.462±0.3 mM sucralose, well below the concentration in common cola beverages (0.55–0.67 mM). A fixed concentration of caffeine, corresponding to the concentration of caffeine in a common cola beverage (0.67 mM) was added to the sweeteners and a non-caffeinated cola beverage. Subjects could distinguish between caffeinated and non-caffeinated sweeteners (p<0.001), but all subjects failed to distinguish between caffeinated and non-caffeinated cola beverage (p=1.0). Caffeine has no flavor activity in soft-drinks yet will induce a physiologic and psychologic desire to consume the drink.

A psychophysical investigation of binary bitter-compound interactions

The aim of this study was to determine if taste interactions occur when bitter stimuli are mixed. Eight bitter stimuli were employed: denatonium benzoate (DB), quinine-HCl (QHCl), sucrose octaacetate (SOA), urea, L-tryptophan (L-trp), L-phenylalanine (L-phe), ranitidine-HCl, and Tetralone. The first experiment constructed individual psychophysical curves for each subject (n = 19) for each compound to account for individual differences in sensitivities when presenting bitter compounds in experiment 2. Correlation analysis revealed two groupings of bitter compounds at low intensity (1, L-trp, L-phe, and ranitidine; 2, SOA and QHCl), but the correlations within each group decreased as the perceived intensity increased. In experiment 2, intensity ratings and two-alternative forced-choice discrimination tasks showed that bitter compounds generally combine additively in mixture and do not show interactions with a few specific exceptions. The methods employed detected synergy among sweeteners, but could not detect synergy among these eight bitter compounds. In general, the perceived bitterness of these binary bitter-compound mixtures was an additive function of the total bitter-inducing stimuli in the mouth.

Bitterness suppression with zinc sulfate and na-cyclamate: a model of combined peripheral and central neural approaches to flavor modification

Purpose Zinc sulfate is known to inhibit the bitterness of the antimalarial agent quinine [R. S. J. Keast. The effect of zinc on human taste perception. J. Food Sci. 68:1871–1877 (2003)]. In the present work, we investigated whether zinc sulfate would inhibit other bitter-tasting compounds and pharmaceuticals. The utility of zinc as a general bitterness inhibitor is compromised, however, by the fact that it is also a good sweetness inhibitor [R. S. J. Keast, T. Canty, and P. A. S. Breslin. Oral zinc sulfate solutions inhibit sweet taste perception. Chem. Senses 29:513–521 (2004)] and would interfere with the taste of complex formulations. Yet, zinc sulfate does not inhibit the sweetener Na-cyclamate. Thus, we determined whether a mixture of zinc sulfate and Na-cyclamate would be a particularly effective combination for bitterness inhibition (Zn) and masking (cyclamate).

Method We used human taste psychophysical procedures with chemical solutions to assess bitterness blocking.

Results Zinc sulfate significantly inhibited the bitterness of quinine–HCl, Tetralone, and denatonium benzoate (DB) (p < 0.05), but had no significant effect on the bitterness of sucrose octa-acetate, pseudoephedrine (PSE), and dextromethorphan. A second experiment examined the influence of zinc sulfate on bittersweet mixtures. The bitter compounds were DB and PSE, and the sweeteners were sucrose (inhibited by 25 mM zinc sulfate) and Na-cyclamate (not inhibited by zinc sulfate). The combination of zinc sulfate and Na-cyclamate most effectively inhibited DB bitterness (86%) (p < 0.0016), whereas the mixture's inhibition of PSE bitterness was not different from that of Na-cyclamate alone.

Conclusion A combination of Na-cyclamate and zinc sulfate was most effective at inhibiting bitterness. Thus, the combined use of peripheral oral and central cognitive bitterness reduction strategies should be particularly effective for improving the flavor profile of bitter-tasting foods and pharmaceutical formulations.

Oral zinc sulfate solutions inhibit sweet taste perception

We investigated the ability of zinc sulfate (5, 25, 50 mM) to inhibit the sweetness of 12 chemically diverse sweeteners, which were all intensity matched to 300 mM sucrose [800 mM glucose, 475 mM fructose, 3.25 mM aspartame, 3.5 mM saccharin, 12 mM sodium cyclamate, 14 mM acesulfame-K, 1.04 M sorbitol, 0.629 mM sucralose, 0.375 mM neohesperidin dihydrochalcone (NHDC), 1.5 mM stevioside and 0.0163 mM thaumatin]. Zinc sulfate inhibited the sweetness of most compounds in a concentration dependent manner, peaking with 80% inhibition by 50 mM. Curiously, zinc sulfate never inhibited the sweetness of Na-cyclamate. This suggests that Na-cyclamate may access a sweet taste mechanism that is different from the other sweeteners, which were inhibited uniformly (except thaumatin) at every concentration of zinc sulfate. We hypothesize that this set of compounds either accesses a single receptor or multiple receptors that are inhibited equally by zinc sulfate at each concentration.

The influence of sodium salts on binary mixtures of bitter-tasting compounds

In order to study potential mixture interactions among bitter compounds, selected sodium salts were added to five compounds presented either alone or as binary bitter- ompound mixtures. Each compound was tested at a concentration that elicited ‘weak’ perceived bitterness. The bitter compounds were mixed at these concentrations to form a subset of possible binary mixtures. For comparison, the concentration of each solitary compound was doubled to measure bitterness inhibition at the higher intensity level elicited by the mixtures. The following sodium salts were tested for bitterness inhibition: 100 mM sodium chloride (salty), 100 mM sodium gluconate (salty), 100 and 20 mM monosodium glutamate (umami), and 50 mM adenosine monophosphate disodium salt (umami). Sucrose (sweet) was also employed as a bitterness suppressor. The sodium salts differentially suppressed the bitterness of compounds and their binary combinations. Although most bitter compounds were suppressed, the bitterness of tetralone was not suppressed, nor was the bitterness of the binary mixtures that contained it. In general, the percent suppression of binary mixtures of compounds was predicted by the average percent suppression of its two components. Within the constraints of the present study, the bitterness of mixtures was suppressed by sodium salts and sucrose independently, with few bitter interactions. This is consistent with observations that the bitter taste system integrates the bitterness of multi-compound solutions linearly.

Relationship between stress, eating behavior and obesity

Stress is thought to influence human eating behavior and has been examined in animal and human studies. Our understanding of the stress-eating relation is confounded by limitations inherent in the study designs; however, we can make some tentative conclusions that support the notion that stress can influence eating patterns in humans. Stress appears to alter overall food intake in two ways, resulting in under- or overeating, which may be influenced by stressor severity. Chronic life stress seems to be associated with a greater preference for energy- and nutrient-dense foods, namely those that are high in sugar and fat. Evidence from longitudinal studies suggests that chronic life stress may be causally linked to weight gain, with a greater effect seen in men. Stress-induced eating may be one factor contributing to the development of obesity. Future studies that measure biological markers of stress will assist our understanding of the physiologic mechanism underlying the stress-eating relation and how stress might be linked to neurotransmitters and hormones that control appetite.

Role of P-glycoprotein in limiting the brain penetration of glabridin, an active isoflavan from the root of Glycyrrhiza glabra.

Purpose. Glabridin is a major active constituent of Glycyrrhiza glabra which is commonly used in the treatment of cardiovascular and central nervous system (CNS) diseases. Recently, we have found that glabridin is a substrate of P-glycoprotein (PgP/MDR1). This study aimed to investigate the role of PgP in glabridin penetration across the blood–brain barrier (BBB) using several in vitro and in vivo models.
Materials and Methods. Cultured primary rat brain microvascular endothelial cells (RBMVECs) were used in the uptake, efflux and transcellular transport studies. A rat bilateral in situ brain perfusion model was used to investigate the brain distribution of glabridin. The brain and tissue distribution of glabridin in rats with or without coadministered verapamil or quinidine were examined with correction for the tissue residual blood. In addition, the brain distribution of glabridin in mdr1a(-/-) mice was compared with the wild-type mice. Glabridin in various biological matrices was determined by a validated liquid chromatography mass spectrometric method.
Results. The uptake and efflux of glabridin in cultured RBMVECs were ATP-dependent and significantly altered in the presence of a PgP or multi-drug resistance protein (Mrp1/2) inhibitor (e.g. verapamil or MK-571). A polarized transport of glabridin was found in RBMVEC monolayers with
facilitated efflux from the abluminal (BL) to luminal (AP) side. Addition of a PgP or Mrp1/2 inhibitor in both luminal and abluminal sides attenuated the polarized transport across RBMVECs. In a bilateral in situ brain perfusion model, the uptake of glabridin into the cerebrum increased from 0.42 T 0.09% at 1 min to 9.27 T 1.69% (ml/100 g tissue) at 30 min and was significantly greater than that for sucrose. Coperfusion of a PgP or Mrp1/2 inhibitor significantly increased the brain distribution of glabridin by 33.6j142.9%. The rat brain levels of glabridin were only about 27% of plasma levels when corrected by tissue residual blood and it was increased to up to 44% when verapamil or quinidine was coadministered. The area under the brain concentration-time curve (AUC) of glabridin in mdr1a(-/-) mice was 6.0-fold higher than the wild-type mice.
Conclusions. These findings indicate that PgP limits the brain penetration of glabridin through the BBB and PgP may cause drug resistance to glabridin (licorice) therapy for CNS diseases and potential drugglabridin interactions. However, further studies are needed to explore the role of other drug transporters (e.g. Mrp1-4) in restricting the brain penetration of glabridin.

Transport of cryptotanshinone, a major active triterpenoid in Salvia miltiorrhiza Bunge widely used in the treatment of stroke and Alzheimers disease, across the blood-brain

Cryptotanshinone (CTS), a major constituent from the roots of Salvia miltiorrhiza (Danshen), is widely used in the treatment of coronary heart disease, stroke and less commonly Alzheimer's disease. Our recent study indicates that CTS is a substrate for Pglycoprotein (PgP/MDR1/ABCB1). This study has investigated the nature of the brain distribution of CTS across the brain-blood barrier (BBB) using several in vitro and in vivo rodent models. A polarized transport of CTS was found in rat primary microvascular endothelial cell (RBMVEC) monolayers, with facilitated efflux from the abluminal side to luminal side. Addition of a PgP (e.g. verapamil and quinidine) or multi-drug resistance protein 1/2 (MRP1/2) inhibitor (e.g. probenecid and MK-571) in both luminal and abluminal sides attenuated the polarized transport. In a bilateral in situ brain perfusion model, the uptake of CTS into the cerebrum increased from 0.52 ± 0.1% at 1 min to 11.13 ± 2.36 ml/100 g tissue at 30 min and was significantly greater than that of sucrose. Co-perfusion of a PgP/MDR1 (e.g. verapamil) or MRP1/2 inhibitor (e.g. probenecid) significantly increased the brain distribution of CTS by 35.1-163.6%. The brain levels of CTS were only about 21% of those in plasma, and were significantly increased when coadministered with verapamil or probenecid in rats. The brain levels of CTS in rats subjected to middle cerebral artery occlusion and rats treated with quinolinic acid (a neurotoxin) were about 2- to 2.5-fold higher than the control rats. Moreover, the brain levels in mdr1a(-/-) and mrp1(-/-) mice were 10.9- and 1.5-fold higher than those in the wild-type mice, respectively. Taken collectively, these findings indicate that PgP and Mrp1 limit the brain penetration of CTS in rodents, suggesting a possible role of PgP and MRP1 in limiting the brain penetration of CTS in patients and causing drug resistance to Danshen therapy and interactions with conventional drugs that are substrates of PgP and MRP1. Further studies are needed to explore the role of other drug transporters in restricting the brain penetration of CTS and the clinical relevance.