Co-ingestion of whey protein hydrolysate with milk minerals rich in calcium potently stimulates glucagon-like peptide-1 secretion: an RCT in healthy adults.

PURPOSE: To examine whether calcium type and co-ingestion with protein alter gut hormone availability. METHODS: Healthy adults aged 26 ± 7 years (mean ± SD) completed three randomized, double-blind, crossover studies. In all studies, arterialized blood was sampled postprandially over 120 min to determine GLP-1, GIP and PYY responses, alongside appetite ratings, energy expenditure and blood pressure. In study 1 (n = 20), three treatments matched for total calcium content (1058 mg) were compared: calcium citrate (CALCITR); milk minerals rich in calcium (MILK MINERALS); and milk minerals rich in calcium plus co-ingestion of 50 g whey protein hydrolysate (MILK MINERALS + PROTEIN). In study 2 (n = 6), 50 g whey protein hydrolysate (PROTEIN) was compared to MILK MINERALS + PROTEIN. In study 3 (n = 6), MILK MINERALS was compared to the vehicle of ingestion (water plus sucralose; CONTROL). RESULTS: MILK MINERALS + PROTEIN increased GLP-1 incremental area under the curve (iAUC) by ~ ninefold (43.7 ± 11.1 pmol L-1 120 min; p < 0.001) versus both CALCITR and MILK MINERALS, with no difference detected between CALCITR (6.6 ± 3.7 pmol L-1 120 min) and MILK MINERALS (5.3 ± 3.5 pmol L-1 120 min; p > 0.999). MILK MINERALS + PROTEIN produced a GLP-1 iAUC ~ 25% greater than PROTEIN (p = 0.024; mean difference: 9.1 ± 6.9 pmol L-1 120 min), whereas the difference between MILK MINERALS versus CONTROL was small and non-significant (p = 0.098; mean difference: 4.2 ± 5.1 pmol L-1 120 min). CONCLUSIONS: When ingested alone, milk minerals rich in calcium do not increase GLP-1 secretion compared to calcium citrate. Co-ingesting high-dose whey protein hydrolysate with milk minerals rich in calcium increases postprandial GLP-1 concentrations to some of the highest physiological levels ever reported. Registered at ClinicalTrials.gov: NCT03232034, NCT03370484, NCT03370497.

An investigation into the relationship between plain water intake and glycated Hb (HbA1c): a sex-stratified, cross-sectional analysis of the UK National Diet and Nutrition Survey (2008-2012).

The aim of this study was to analyse the association between plain water intake and glycated Hb (HbA1c) in the National Diet and Nutrition Survey (2008-2012) rolling survey. These data included diet (4-d diaries) and HbA1c (fasted blood sample) measures of 456 men and 579 women aged 44 (sd 18) years with full information on covariates of interest (age, ethnicity, BMI, smoking status, education, other beverage intake, energy intake and fibre). Data were analysed using sex-stratified linear and logistic regressions modelling the associations of cups per d (240 ml) of plain water with HbA1c, and odds of HbA1c≥5·5 %, respectively. Substitution analyses modelled the replacement of sugar-sweetened beverages, fruit juice and artificially sweetened beverages with plain water. After adjustment, 1 cup/d of plain water was associated with a -0·04 % lower HbA1c (95 % CI -0·07, -0·02) in men. In logistic regression, men had a 22 % (95 % CI 10, 32 %) reduced odds of HbA1c≥5·5 %/cup per d of plain water. There was no evidence of an association with either HbA1c or odds of HbA1c≥5·5 % in women. None of the substitution models was associated with a change in odds of HbA1c≥5·5 %. Plain water intake was associated with lower HbA1c in men but not in women. Substituting water for specific beverages was not associated with a reduced odds of HbA1c≥5·5 %, suggesting that the addition of water is the more pertinent factor. Future trials should test whether the relationships between water intake and HbA1c is causal as this could be a cost-effective and simple health intervention.

The association between water intake and future cardiometabolic disease outcomes in the Malmö Diet and Cancer cardiovascular cohort.

The aim of this study was to explore the longitudinal association between reported baseline water intake and incidence of coronary artery disease (CAD) and type 2 diabetes in the Malmö Diet and Cancer Cohort (n = 25,369). Using cox proportional hazards models, we separately modelled the effect of plain and total (all water, including from food) water on CAD and type 2 diabetes risk, whilst adjusting for age, sex, diet collection method, season, smoking status, alcohol intake, physical activity, education level, energy intake, energy misreporting, body mass index, hypertension, lipid lowering medication, apolipoprotein A, apolipoprotein B, and dietary variables. Sensitivity analyses were run to assess validity. After adjustment, no association was found between tertiles of plain or total water intake and type 2 diabetes risk. For CAD, no association was found comparing moderate to low intake tertiles from plain or total water, however, risk of CAD increased by 12% (95% CI 1.03, 1.21) when comparing high to low intake tertiles of plain water, and by 17% (95% CI 1.07, 1.27) for high versus low tertiles of total water. Sensitivity analyses were largely in agreement. Overall, baseline water intake was not associated with future type 2 diabetes risk, whilst CAD risk was higher with higher water intakes. Our findings are discordant with prevailing literature suggesting higher water intakes should reduce cardiometabolic risk. These findings may be an artefact of limitations within the study, but future research is needed to understand if there is a causal underpinning.

Effects of neuromuscular electrical stimulation on energy expenditure and postprandial metabolism in healthy men.

It is unclear whether neuromuscular electrical stimulation (NMES) has meaningful metabolic effects when users have the opportunity to self-select the intensity to one that can be comfortably tolerated. Nine healthy men aged 28 ± 9 y (mean ± SD) with a body mass index 22.3 ± 2.3 kg/m2 completed 3 trials involving a 2-h oral glucose tolerance test whilst, in a randomised counterbalanced order, (1) sitting motionless (SIT), (2) standing motionless (STAND); and (3) sitting motionless with NMES of quadriceps and calves at a self-selected tolerable intensity. The mean (95% confidence interval [CI]) total energy expenditure was greater in the NMES trial (221 [180-262] kcal/2 h) and STAND trial (178 [164-191] kcal/2 h) than during SIT (159 [150-167] kcal/2 h) (both, p < 0.05). This was primarily driven by an increase in carbohydrate oxidation in the NMES and STAND trials compared with the SIT trial (p < 0.05). Postprandial insulin iAUC was lower in both NMES and STAND compared with SIT (16.4 [7.7-25.1], 17 [7-27] and 22.6 [10.8-34.4] nmol·120 min/L, respectively; both, p < 0.05). Compared with sitting, both NMES and STAND increased energy expenditure and whole-body carbohydrate oxidation and reduced postprandial insulin concentrations in healthy men, with more pronounced effects seen with NMES. Self-selected NMES is a potential strategy for improving metabolic health. This trial is registered at ClinicalTrials.gov (ID: NCT04389736). Novelty: NMES at a comfortable intensity enhances energy expenditure and carbohydrate oxidation, and reduces postprandial insulinemia. Thus, self-selected NMES represents a potential strategy to improve metabolic health.

The effect of hydration status on plasma FGF21 concentrations in humans: A subanalysis of a randomised crossover trial.

AIM: Fibroblast growth factor 21 (FGF21) has recently been implicated in thirst in rodent models. The mechanisms for this are currently uncertain, and it is unclear whether hydration status can alter FGF21 concentrations, potentially providing an additional mechanism by which hypohydration induces thirst. The aim of this study is therefore to understand whether hydration status can alter circulating FGF21 in humans. METHODS: Using a heat tent and fluid restriction, we induced hypohydration (1.9% body mass loss) in 16 healthy participants (n = 8 men), and compared their glycaemic regulation to a rehydration protocol (heat tent and fluid replacement) in a randomised crossover design. RESULTS: After the hypohydration procedure, urine specific gravity, urine and serum osmolality, and plasma copeptin (as a marker for arginine vasopressin) increased as expected, with no change after the rehydration protocol. In the fasted state, the median paired difference in plasma FGF21 concentrations from the rehydrated to hypohydrated trial arm was -37 (interquartile range -125, 10) pg∙mL-1(P = 0.278), with average concentrations being 458 ± 462 pg∙mL-1 after hypohydration and 467 ± 438 pg∙mL-1 after rehydration; mean difference -9 ± 173 pg∙mL-1. CONCLUSION: To our knowledge, these are the first causal data in humans investigating hydration and FGF21, demonstrating that an acute bout of hypohydration does not impact fasted plasma FGF21 concentrations. These data may suggest that whilst previous research has found FGF21 administration can induce thirst and drinking behaviours, a physiological state implicated in increased thirst (hypohydration) does not appear to impact plasma FGF21 concentrations in humans.

Effect of Plain Versus Sugar-Sweetened Breakfast on Energy Balance and Metabolic Health: A Randomized Crossover Trial.

OBJECTIVE: This study investigated the effect of 3 weeks of high-sugar ("Sweet") versus low-sugar ("Plain") breakfast on energy balance, metabolic health, and appetite. METHODS: A total of 29 healthy adults (22 women) completed this randomized crossover study. Participants had pre- and postintervention appetite, health, and body mass outcomes measured, and they recorded diet, appetite (visual analogue scales), and physical activity for 8 days during each intervention. Interventions were 3 weeks of isoenergetic Sweet (30% by weight added sugar; average 32 g of sugar) versus Plain (no added sugar; average 8 g of sugar) porridge-based breakfasts. RESULTS: Pre- to postintervention changes in body mass were similar between Plain (Δ 0.1 kg; 95% CI: -0.3 to 0.5 kg) and Sweet (Δ 0.2 kg; 95% CI: -0.2 to 0.5 kg), as were pre- to postintervention changes for biomarkers of health (all P ≥ 0.101) and psychological appetite (all P ≥ 0.152). Energy, fat, and protein intake was not statistically different between conditions. Total carbohydrate intake was higher during Sweet (287 ± 82 g/d vs. 256 ± 73 g/d; P = 0.009), driven more by higher sugar intake at breakfast (116 ± 46 g/d vs. 88 ± 38 g/d; P < 0.001) than post-breakfast sugar intake (Sweet 84 ± 42 g/d vs. Plain 80 ± 37 g/d; P = 0.552). Participants reported reduced sweet desire immediately after Sweet but not Plain breakfasts (trial × time P < 0.001). CONCLUSIONS: Energy balance, health markers, and appetite did not respond differently to 3 weeks of high- or low-sugar breakfasts.

Hydration, Arginine Vasopressin, and Glucoregulatory Health in Humans: A Critical Perspective.

Glucoregulatory diseases, such as type 2 diabetes are currently a key public health priority. Public health messages have started to include the addition of water in their dietary guidelines. Such guidelines however are not based on causal evidence pertaining to the health effects of increased water intake, but rather more heavily based upon non-causal or mechanistic data. One line of thinking linking fluid intake and health is that hypohydration induces elevated blood concentrations of arginine vasopressin (AVP). Research in the 1970s and 1980s implicated AVP in glucoregulation, supported by observational evidence. This important area of research subsequently appeared to stop until the 21st century during which interest in hypertonic saline infusion studies, animal AVP receptor knockout models, dietary and genetic associations, and human interventions manipulating hydration status have resurged. This narrative review briefly describes and critically evaluates the usefulness of the current AVP-glucoregulatory research. We offer suggestions on how to test the independent glucoregulatory effects of body water changes compared to elevated circulating AVP concentrations, such as investigating hydration manipulations using 3,4-Methylenedioxymethamphetamine. Whilst much research is still needed before making firm conclusions, the current evidence suggests that although AVP may be partially implicated in glucoregulation, more ecologically valid models using human participants suggests this effect might be independent of the hydration status. The key implication of this hypothesis if confirmed in future research is that manipulating the hydration status to reduce circulating AVP concentrations may not be an effective method to improve glucoregulatory health.

Effect of acute hypohydration on glycemic regulation in healthy adults: a randomized crossover trial.

The aim of this study was to investigate the acute effect of hydration status on glycemic regulation in healthy adults and explore underlying mechanisms. In this randomized crossover trial, 16 healthy adults (8 men, 8 women) underwent an oral glucose tolerance test (OGTT) when hypohydrated and rehydrated after 4 days of pretrial standardization. One day before OGTT, participants were dehydrated for 1 h in a heat tent with subsequent fluid restriction (HYPO) or replacement (RE). The following day, an OGTT was performed with metabolic rate measurements and pre- and post-OGTT muscle biopsies. Peripheral quantitative computer tomography thigh scans were taken before and after intervention to infer changes in cell volume. HYPO (but not RE) induced 1.9% (SD 1.2) body mass loss, 2.9% (SD 2.7) cell volume reduction, and increased urinary hydration markers, serum osmolality, and plasma copeptin concentration (all P ≤ 0.007). Fasted serum glucose [HYPO 5.10 mmol/l (SD 0.42), RE 5.02 mmol/l (SD 0.40); P = 0.327] and insulin [HYPO 27.1 pmol/l (SD 9.7), RE 27.6 pmol/l (SD 9.2); P = 0.809] concentrations were similar between HYPO and RE. Hydration status did not alter the serum glucose ( P = 0.627) or insulin ( P = 0.200) responses during the OGTT. Muscle water content was lower before OGTT after HYPO compared with RE [761 g/kg wet wt (SD 13) vs. 772 g/kg wet wt (SD 18) RE] but similar after OGTT [HYPO 779 g/kg wet wt (SD 15) vs. RE 780 g/kg wet wt (SD 20); time P = 0.011; trial × time P = 0.055]. Resting energy expenditure was similar between hydration states (stable between -1.21 and 5.94 kJ·kg-1·day-1; trial P = 0.904). Overall, despite acute mild hypohydration increasing plasma copeptin concentrations and decreasing fasted cell volume and muscle water, we found no effect on glycemic regulation. NEW & NOTEWORTHY We demonstrated for the first time that an acute bout of hypohydration does not impact blood sugar control in healthy adults. Physiological responses to mild hypohydration (<2% body mass loss) caused an elevation in copeptin concentrations similar to that seen in those with diabetes as well as reducing cell volume by ~3%; both of these changes had been hypothesized to cause a higher blood sugar response.

Hydration status affects thirst and salt preference but not energy intake or postprandial ghrelin in healthy adults: A randomised crossover trial.

BACKGROUND: Few studies have investigated the effect of hydration status on appetite for food in healthy adults. Prior work suggests hydration status does not alter appetite or energy intake, with mixed findings regarding appetite hormone secretion. However, an extensive investigation into both the psychological and physiological appetitive responses to hydration status has never been conducted. OBJECTIVE: To investigate the effect of hydration status on multiple facets of appetite. DESIGN: After 3 days pre-trial standardization, a range of appetite tasks were conducted when hypohydrated (HYPO) and euhydrated (EUHY) in 16 healthy participants (8 men). Hydration status was manipulated via dehydration in a heat tent for 60 min and subsequent fluid restriction (HYPO) or replacement (EUHY). The next day, a food reward computer task was completed followed by an ad libitum pasta meal. Pre- and post-prandial visual analogue scales assessing hunger, fullness, and flavour desires (sweet, salty, savoury and fatty) were additionally completed. Blood samples were taken the previous day before the hydration interventions in a euhydrated state, and in the fasted and post-prandial state during HYPO and EUHY. RESULTS: HYPO induced -1.9 ±â€¯1.2% body mass change, compared to -0.2 ±â€¯0.6% , with accompanying changes in markers of hypohydration which were not seen during EUHY. A higher desire for foods was associated with a higher water content but the association was weaker in EUHY compared to HYPO, (ß= -0.33 mm/g of food water content, p < 0.001) in the food reward task. Visual analogue scales showed similar hunger and fullness between interventions, but during HYPO there was consistently higher thirst (average range in difference 27-32 mm across all time points) and lower fasted desire for salt (-23, 95% CI -10, -35 mm). Ad libitum energy intake (HYPO 1953 ±â€¯742 kJ, EUHY 2027 ±â€¯926 kJ; p = 0.542) and post-prandial ghrelin concentrations (HYPO 180 ±â€¯65 pg mL-1, EUHY 188 ±â€¯71 pg mL-1; p = 0.736) were similar by hydration status. CONCLUSIONS: An acute manipulation to hydration status altered desire for salt and foods of differing water contents, but did not influence energy intake at an ad libitum pasta meal. Further research should investigate whether these appetites would alter food choice.

The perceived feasibility of methods to reduce publication bias.

Publication bias is prevalent within the scientific literature. Whilst there are multiple ideas on how to reduce publication bias, only a minority of journals have made substantive changes to address the problem. We aimed to explore the perceived feasibility of strategies to reduce publication bias by gauging opinions of journal editors (n = 73) and other academics/researchers (n = 160) regarding nine methods of publishing and peer-reviewing research: mandatory publication, negative results journals/articles, open reviewing, peer-review training and accreditation, post-publication review, pre-study publication of methodology, published rejection lists, research registration, and two-stage review. Participants completed a questionnaire asking both quantitative (multiple choice or Likert scales) and qualitative (open-ended) questions regarding the barriers to implementing each suggestion, and their strengths and limitations. Participants were asked to rate the nine suggestions, then choose the method they felt was most effective. Mandatory publication was most popularly selected as the 'most effective' method of reducing publication bias for editors (25%), and was the third most popular choice for academics/researchers (14%). The most common selection for academics/researchers was two-stage review (26%), but fewer editors prioritised this (11%). Negative results journals/articles were the second and third most common choices for academics/researchers (21%) and editors (16%), respectively. Editors more commonly chose research registration as 'most effective' (21%), which was favoured by only 6% of academics/researchers. Whilst mandatory publication was generally favoured by respondents, it is infeasible to trial at a journal level. Where suggestions have already been implemented (e.g. negative results journals/articles, trial registration), efforts should be made to objectively assess their efficacy. Two-stage review should be further trialled as its popularity amongst academics/researchers suggests it may be well received, though editors may be less receptive. Several underlying barriers to change also emerged, including scientific culture, impact factors, and researcher training; these should be further explored to reduce publication bias.

Higher plain water intake is associated with lower type 2 diabetes risk: a cross-sectional study in humans.

The aim of this study was to investigate the relationship between plain water intake and type 2 diabetes (T2D) risk. It was hypothesized that higher plain water intake would be associated with a lower T2D risk score. One hundred thirty-eight adults from Southwest and Southeast England answered a cross-sectional online survey assessing T2D risk (using the Diabetes UK risk assessment); physical activity (using the short International Physical Activity Questionnaire); and consumption of fruits, vegetables, and beverages (using an adapted version of the Cambridge European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire). There was a trend for differences in mean plain water intake between those stratified as having low, increased, moderate, or high risk of T2D; but these did not achieve significance (P = .084). However, plain water intake was significantly negatively correlated with T2D risk score (τ = -0°180, P = .005); and for every 240-mL cup of water consumed per day, T2D risk score was reduced by 0.72 point (range, 0-47) (B = -0.03, 95% confidence interval = -0.06 to -0.01, P = .014). The current study has provided preliminary results that are supported by theory; mechanisms need to be explored further to determine the true effect of plain water intake on disease risk. As increasing plain water intake is a simple and cost-effective dietary modification, its impact on T2D risk is important to investigate further in a randomized controlled trial. Overall, this study found that plain water intake had a significant negative correlation with T2D risk score; and regression analysis suggested that water may have a role in reducing T2D risk.