Effects of ingesting beverages containing glycerol and sodium with isomaltulose or sucrose on fluid retention in young adults: a single-blind, randomized crossover trial.

We evaluated changes in hyperhydration and beverage hydration index (BHI, a composite measure of fluid balance after consuming a test beverage relative to water) during resting, induced by the consumption of beverages containing glycerol and sodium supplemented with fast-absorbing sucrose or slow-absorbing isomaltulose. In a randomized crossover, single-blinded protocol (clinical trials registry: UMIN000042644), 14 young physically active adults (three women) consumed 1 L of beverage containing either 7% glycerol + 0.5% sodium (Gly + Na), Gly + Na plus 7% sucrose (Gly + Na + Suc), Gly + Na plus 7% isomaltulose (Gly + Na + Iso), or water (CON) over a 40 min period. We assessed the change in plasma volume (ΔPV), BHI (calculated from cumulative urine output following consumption of water relative to that of the beverage), and blood glucose and sodium for 180 min after initiating ingestion. Total urine volume was reduced in all beverages containing glycerol and sodium compared to CON (all P ≤ 0.002). The addition of isomaltulose increased BHI by ∼45% (3.43 ± 1.0 vs. 2.50 ± 0.7 for Gly + Na, P = 0.011) whereas sucrose did not (2.6 ± 0.6, P = 0.826). The PV expansion was earliest for Gly + Na (30 min), slower for Gly + Na + Suc (90 min), and slowest for Gly + Na + Iso (120 min) with a concomitant lag in the increase of blood glucose and sodium concentrations. Supplementation of beverages containing glycerol and sodium with isomaltulose but not sucrose enhances BHI from those of glycerol and sodium only under a resting state, likely due to the slow absorption of isomaltulose-derived monosaccharides (i.e., glucose and fructose).

Effects of ingestion of isomaltulose beverage on plasma volume and thermoregulatory responses during exercise in the heat.

PURPOSE: Isomaltulose is a low glycemic and insulinaemic carbohydrate increasingly used as an alternative sweetener in commercial beverages. While isomaltulose beverages can improve hydration status compared to sucrose-based beverages, it remains unclear if ingestion of an isomaltulose beverage prior to exercise in the heat may improve plasma volume (PV) and thermoregulatory responses. METHODS: Twelve endurance-trained men consumed a 1L carbohydrate beverage containing either 6.5%-sucrose (SUC) or 6.5%-isomaltulose (ISO) 60 min prior to 5 successive, 15-min bouts of moderate-intensity (60% of their pre-determined maximum oxygen uptake) in the heat (32 °C, 50% relative humidity), each separated by a 5 min rest. A 6th bout was performed, wherein the participant adjusted running speed to maximize distance covered within the 15-min period. The change (Δ) in PV, heart rate (HR), body core (rectal and gastrointestinal) and skin temperatures, and whole-body sweat loss were assessed during each exercise bout. RESULTS: Ingestion of ISO induced a higher ΔPV at 4th bout only (P < 0.001) and lower HR (P = 0.032, main effect of beverage) during exercise compared to those of SUC. Body core and skin temperatures and whole-body sweat loss did not differ between conditions (all P ≥ 0.192, interaction effect). Running distance covered in final exercise bout tended to increase (~ 5%) in ISO versus SUC (P = 0.057, d = 0.64). CONCLUSIONS: Relative to a sucrose-based beverage, ISO ingestion prior to exercise in the heat reduced cardiovascular strain by preserving PV and attenuating HR, albeit with no corresponding benefit on thermoregulatory function. The former response may facilitate improvements in exercise performance.

Comparison of hydration efficacy of carbohydrate-electrolytes beverages consisting of isomaltulose and sucrose in healthy young adults: A randomized crossover trial.

Isomaltulose is a low glycemic and insulinaemic carbohydrate now used as an alternative sweetener in beverages. However, it remains unclear if hydration status may be impacted differently with the consumption of beverages containing isomaltulose as compared to sucrose, a common beverage sweetener. Thirteen young adults (7 women) consumed 1 L of a carbohydrate beverage (with low electrolyte content) containing either 6.5%-sucrose, 6.5%-isomaltulose, or water within a 15 min period. For each beverage, beverage hydration index (BHI, a composite measure of fluid balance after consuming a test beverage relative to water) was calculated from urine volume produced over a 3 h period following ingestion of the carbohydrate beverages relative to water. The change in plasma volume (ΔPV), blood glucose, and lactate concentrations were assessed every 30 min post-beverage consumption. Isomaltulose ingestion attenuated urine production as compared to water and sucrose (P ≤ 0.005) over the 3 h post-ingestion period. However, no differences were observed between sucrose and water (P = 0.055). BHI was 1.53 ± 0.44 for isomaltulose (P ≤ 0.022 vs. sucrose and water) and 1.20±0.29 for sucrose (P = 0.210 vs. water). A transient reduction in ΔPV was observed following the ingestion of the isomaltulose beverage (at 30 min, P = 0.007 vs. sucrose). Thereafter, no differences in ΔPV between beverages were measured. Increases in blood glucose and lactate, indices of absorption and utility of glucose, were delayed in the isomaltulose as compared to sucrose beverage. In summary, we demonstrated a greater BHI with a carbohydrate-electrolyte beverage containing isomaltulose as compared to sucrose. This may in part be attributed to a delayed absorption of isomaltulose reducing diuresis.

Comparisons of isomaltulose, sucrose, and mixture of glucose and fructose ingestions on postexercise hydration state in young men.

PURPOSE: Isomaltulose is a low glycemic and insulinaemic carbohydrate available as a constituent in sports drink. However, it remains unclear whether postexercise rehydration achieved by isomaltulose drink ingestion alone differs as compared to other carbohydrates. METHODS: Thirteen young men performed intermittent exercise in the heat (35 °C and relative humidity 40%) to induce a state of hypohydration as defined by a 2% loss in body mass. Thereafter, participants were rehydrated by ingesting drinks equal to the volume of body mass loss with either a mixture of 3.25% glucose and 3.25% fructose, 6.5% sucrose (SUC), or 6.5% isomaltulose (ISO) within the first 30 min of a 3-h recovery. The change in plasma volume (ΔPV) from pre-exercise baseline, blood glucose, and plasma insulin concentration were assessed every 30-min. RESULTS: ΔPV was lower in ISO as compared to SUC until 90 min of the recovery (all P ≤ 0.038) with no difference thereafter (all P ≥ 0.391). The ΔPV were paralleled by concomitant changes in blood glucose levels that were greater in ISO as compared to other drinks after 90 min of the recovery (all P ≤ 0.035). Plasma insulin secretion, which potentially enhances renal sodium reabsorption and fluid retention, did not differ between the trials (interaction, P = 0.653). ISO induced a greater net fluid volume retention as compared to SUC (P = 0.010). CONCLUSION: We showed that rehydration with an isomaltulose drink following exercise-heat stress induces comparable recovery of PV and a greater net fluid retention as compared to other drinks, albeit this response is delayed. The delayed water transport along with glucose absorption may modulate this response. This trial was registered in 25th Sep 2019 at https://www.umin.ac.jp/ as UMIN000038099. (249/250).

Effects of Isomaltulose Ingestion on Thermoregulatory Responses during Exercise in a Hot Environment.

Isomaltulose is a low glycemic and insulinemic carbohydrate available as a constituent of sports drinks. However, it remains unclear whether thermoregulatory responses (sweating and cutaneous vasodilation) after isomaltulose drink ingestion differ from those of sucrose and water during exercise in a hot environment. Ten young healthy males consumed 10% sucrose, 10% isomaltulose, or water drinks. Thirty-five minutes after ingestion, they cycled for fifteen minutes at 75% peak oxygen uptake in a hot environment (30 °C, 40% relative humidity). Sucrose ingestion induced greater blood glucose concentration and insulin secretion at the pre-exercise state, compared with isomaltulose and/or water trials, with no differences during exercise in blood glucose. Change in plasma volume did not differ between the three trials throughout the experiment, but both sucrose and isomaltulose ingestions similarly increased plasma osmolality, as compared with water (main beverage effect, p = 0.040)-a key response that potentially delays the onset of heat loss responses. However, core temperature thresholds and slopes for heat loss responses were not different between the trials during exercise. These results suggest that ingestion of isomaltulose beverages induces low glycemic and insulinemic states before exercise but does not alter thermoregulatory responses during exercise in a hot environment, compared with sucrose or water.

Evaluation of Postprandial Glycemic Response and Physical Properties of High-Amylose Rice "Koshinokaori".

This study evaluated the postprandial glycemic response and physical properties of the high-amylose rice, Koshinokaori (KK), cooked under different conditions. Twelve healthy subjects (Japanese, 6 males, 6 females) were given cooked, white KK rice or tomato chicken rice (TCR) using KK rice. The Japanese standard rice, Koshihikari (KH), was used as reference. All meals contained the same amount (50 g) of available carbohydrate. Blood glucose levels were measured at 0 (fasting), 15, 30, 45, 60, 90, and 120 min after each meal. The results from the cooked, white KK rice showed a significant difference in blood glucose variation at 60, 90, and 120 min and the incremental area under the curve (IAUC) of blood glucose concentration for KK cooked at optimal water to rice ratio was observed. Blood glucose variation and IAUC after intake of TCR-KK rice was lower than that after TCR-KH rice intake. Addition of 5% trehalose to KK rice resulted in a smaller decrease in adhesiveness and stickiness of cooked rice after 180 min at 20ºC. The addition of 5% trehalose to KK rice also produced favorable results in the sensory evaluation. KK rice produces favourable postprandial glycemic responses and physical properties under varied cooking condition and thus, may be beneficial in the prevention of lifestyle-related diseases such as type 2 diabetes.

Effects of isomaltulose ingestion on postexercise hydration state and heat loss responses in young men.

NEW FINDINGS: What is the central question of this study? What are the effects of isomaltulose, an ingredient in carbohydrate-electrolyte beverages to maintain glycaemia and attenuate the risk of dehydration during exercise heat stress, on postexercise rehydration and physiological heat loss responses? What is the main finding and its importance? Consumption of a 6.5% isomaltulose-electrolyte beverage following exercise heat stress restored hydration following a 2 h recovery as compared to a 2% solution or water only. While the 6.5% isomaltulose-electrolytes increased plasma volume and plasma osmolality, which are known to modulate postexercise heat loss, sweating and cutaneous vascular responses did not differ between conditions. Consequently, ingestion beverages containing 6.5% isomaltulose-electrolytes enhanced postexercise rehydration without affecting heat loss responses. ABSTRACT: Isomaltulose is a disaccharide carbohydrate widely used during exercise to maintain glycaemia and hydration. We investigated the effects of ingesting a beverage containing isomaltulose and electrolytes on postexercise hydration state and physiological heat loss responses. In a randomized, single-blind cross-over design, 10 young healthy men were hypohydrated by performing up to three 30 min successive moderate-intensity (50% heart rate reserve) bouts of cycling, each separated by 10 min, while wearing a water-perfusion suit heated to 45°C. The protocol continued until a 2% reduction in body mass was achieved. Thereafter, participants performed a final 15 min moderate-intensity exercise bout followed by a 2 h recovery. Following cessation of exercise, participants ingested a beverage consisting of (i) water only (Water), (ii) 2% isomaltulose (CHO-2%), or (iii) 6.5% isomaltulose (CHO-6.5%) equal to the volume of 2% body mass loss within the first 30 min of the recovery. Changes in plasma volume (ΔPV) after fluid ingestion were greater for CHO-6.5% compared with CHO-2% (120 min postexercise) and Water (90 and 120 min) (all P ≤ 0.040). Plasma osmolality remained elevated with CHO-6.5% compared with consumption of the other beverages at 30 and 90 min postexercise (all P ≤ 0.050). Urine output tended to be reduced with CHO-6.5% compared to other fluid conditions (main effect, P = 0.069). Rectal and mean skin temperatures, chest sweat rate and cutaneous perfusion did not differ between conditions (all P > 0.05). In conclusion, compared with CHO-2% and Water, consuming a beverage consisting of CHO-6.5% and electrolytes during recovery under heat stress enhances PV recovery without modulating physiological heat loss responses.

Evolutionarily conserved domain of heat shock transcription factor negatively regulates oligomerization and DNA binding.

Heat shock transcription factor (HSF) regulates the expression of genes encoding molecular chaperones and stress-responsive proteins. Conversion of HSF from a monomer to a homotrimer or heterotrimer is essential for its binding to heat shock elements (HSEs) comprised of inverted repeats of the pentamer nGAAn. Here, we constructed various human HSF1 derivatives and analyzed their transcriptional activity through the continuously and discontinuously arranged nGAAn units. We identified a short stretch of amino acids that inhibits the activation ability of HSF1, especially through discontinuous HSEs. This stretch is conserved in HSFs of various organisms, interacts with the hydrophobic repeat regions that mediate HSF oligomerization, and impedes homotrimer formation and DNA binding. This conserved domain plays an important role in maintaining HSF in an inactive monomeric form.

Binding affinities and interactions among different heat shock element types and heat shock factors in rice (Oryza sativa L.).

Binding of heat shock factors (Hsfs) to heat shock elements (HSEs) leads to transcriptional regulation of heat shock genes. Genome-wide, 953 rice genes contain perfect-type, 695 genes gap-type and 1584 genes step-type HSE sequences in their 1-kb promoter region. The rice genome contains 13 class A, eight class B and four class C Hsfs (OsHsfs) and has OsHsf26 (which is of variant type) genes. Chemical cross-linking analysis of in vitro synthesized OsHsf polypeptides showed formation of homotrimers of OsHsfA2c, OsHsfA9 and OsHsfB4b proteins. Binding analysis of polypeptides with oligonucleotide probes containing perfect-, gap-, and step-type HSE sequences showed that OsHsfA2c, OsHsfA9 and OsHsfB4b differentially recognize various model HSEs as a function of varying reaction temperatures. The homomeric form of OsHsfA2c and OsHsfB4b proteins was further noted by the bimolecular fluorescence complementation approach in onion epidermal cells. In yeast two-hybrid assays, OsHsfB4b showed homomeric interaction as well as distinct heteromeric interactions with OsHsfA2a, OsHsfA7, OsHsfB4c and OsHsf26. Transactivation activity was noted in OsHsfA2c, OsHsfA2d, OsHsfA9, OsHsfC1a and OsHsfC1b in yeast cells. These differential patterns pertaining to binding with HSEs and protein-protein interactions may have a bearing on the cellular functioning of OsHsfs under a range of different physiological and environmental conditions.

Diversity in DNA recognition by heat shock transcription factors (HSFs) from model organisms.

Heat shock transcription factor (HSF), an evolutionarily conserved heat-responsive regulator, binds to heat shock elements (HSEs) comprising continuous inverted repeats of the pentamer nGAAn. Here, we analyzed DNA-binding ability, particularly for the discontinuously arranged nGAAn units, of HSFs from various organisms, including Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, and Danio rerio. Among these, only C. elegans HSF failed to bind the discontinuous nGAAn units, which suggests that the target genes of HSFs in many, but not all, organisms contain discontinuous HSEs, as well as continuous HSEs. Further analysis of alternatively spliced HSF isoforms showed the importance of the C-terminal region in HSF-HSE interaction.

Novel aspects of heat shock factors: DNA recognition, chromatin modulation and gene expression.

Heat shock factor (HSF) is an evolutionarily conserved stress-response regulator that activates the transcription of heat shock protein genes, whose products maintain protein homeostasis under normal physiological conditions, as well as under conditions of stress. The promoter regions of the target genes contain a heat shock element consisting of multiple inverted repeats of the pentanucleotide sequence nGAAn. A single HSF of yeast can bind to heat shock elements that differ in the configuration of the nGAAn units and can regulate the transcription of various genes that function not only in stress resistance, but also in a broad range of biological processes. Mammalian cells have four HSF family members involved in different, but in some cases similar, biological functions, including stress resistance, cell differentiation and development. Mammalian HSF family members exhibit differential specificity for different types of heat shock elements, which, together with cell type-specific expression of HSFs is important in determining the target genes of each HSF. This minireview focuses on the molecular mechanisms of DNA recognition, chromatin modulation and gene expression by yeast and mammalian HSFs.

DNA-binding and transcriptional activities of human HSF4 containing mutations that associate with congenital and age-related cataracts.

Heat shock transcription factor HSF4 is necessary for ocular lens development and fiber cell differentiation. Mutations of the human HSF4 gene have been implicated in congenital and age-related cataracts. Here, we show that HSF4 activates transcription of genes encoding crystallins and beaded filament structural proteins in lens epithelial cells. Five missense mutations that have been associated with congenital cataract inhibited DNA-binding of HSF4, which demonstrates the relationship between HSF4 mutations, loss of lens protein gene expression, and cataractogenesis. However, two missense mutations that have been associated with age-related cataract did not or only slightly alter HSF4 activity, implying that other genetic and environmental factors affect the functions of these mutant proteins.

Mutational analysis of human heat-shock transcription factor 1 reveals a regulatory role for oligomerization in DNA-binding specificity.

HSF (heat-shock transcription factor) trimers bind to the HSE (heat-shock element) regulatory sequence of target genes and regulate gene expression. A typical HSE consists of at least three contiguous inverted repeats of the 5-bp sequence nGAAn. Yeast HSF is able to recognize discontinuous HSEs that contain gaps in the array of the nGAAn sequence; however, hHSF1 (human HSF1) fails to recognize such sites in vitro, in yeast and in HeLa cells. In the present study, we isolated suppressors of the temperature-sensitive growth defect of hHSF1-expressing yeast cells. Intragenic suppressors contained amino acid substitutions in the DNA-binding domain of hHSF1 that enabled hHSF1 to regulate the transcription of genes containing discontinuous HSEs. The substitutions facilitated hHSF1 oligomerization, suggesting that the DNA-binding domain is important for this conformational change. Furthermore, other oligomerization-prone derivatives of hHSF1 were capable of recognizing discontinuous HSEs. These results suggest that modulation of oligomerization is important for the HSE specificity of hHSF1 and imply that hHSF1 possesses the ability to bind to and regulate gene expression via various types of HSEs in diverse cellular processes.