This study investigated the effect of 3 weeks of high-sugar ("Sweet") versus low-sugar ("Plain") breakfast on energy balance, metabolic health, and appetite.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.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).Energy balance, health markers, and appetite did not respond differently to 3 weeks of high- or low-sugar breakfasts.
Currently, the conceptualisation of thirst is based nearly entirely on osmoregulation, with some acknowledgement of anticipatory-thirst, though with no testable mechanism. Such a model of thirst is unable to explain many thirst-related phenomena, such as why drinking can occur with hypotonicity, or how quantity of intake at a drinking occasion is regulated. Herein, I aim to unify various lines of thinking from different disciplines surrounding thirst and body water regulation by presenting a four-compartment model comprising of both primary and secondary thirsts: true-thirst (osmo-regulated); contextual-thirst (e.g. mouth-breathing); pharmacological-thirst (induced from drugs); and impulsive-thirst (everyday spontaneous drinking). Within this framework, a differentiation of thirst and dry mouth is presented, with further differentiation between dry mouth (‘true-xerostomia’, hyposalivation) and the sensation of dry mouth (‘sensational-xerostomia’, a typically non-overwhelming desire to drink). Based off pharmacological-thirst mechanisms, the cholinergic system is proposed to initiate impulsive-thirst by triggering a (sensation of) dry mouth in everyday life (i.e. without hypertonicity). Following this, psychological food-appetite constructs that are centrally regulated (sensory-specific satiety, palatability, and pleasantness) are applied to thirst to explain quantities of fluid consumed, termination of drinking, and drinking patterns in everyday life, as well as offer further insights into how drinking habits are formed. The historical context is also provided, demonstrating that most of these are not new ideas in isolation, but combining them to create a unified model of thirst has not previously been attempted. Finally, ageing-, exercise-, alcohol-hangover-, and 3,4-methylenedioxymethamphetamine-induced thirst are explained by the model presented, given as examples of dysregulated hydration physiology causing thirst or drinking behaviours currently unexplainable by true osmoregulatory or anticipatory-thirst. Whilst some anomalies still remain, all these examples have some form of dysregulated cholinergic activity as a commonality. It is likely this model is incomplete and ideas for further exploration are presented with the hope that the conceptual model can be investigated, validated, refined, and developed further as appropriate. Overall, this thesis outlines a four-compartment model of thirst regulation (at least partially) explaining several outstanding questions relating to drinking behaviours.
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/m 2 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.
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.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.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.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.
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.
PURPOSE: Prolonged sitting is a major health concern, targeted via government policy and the proliferation of height-adjustable workstations and wearable technologies to encourage standing. Such interventions have the potential to influence energy balance and thus facilitate effective management of body/fat mass. It is therefore remarkable that the energy cost of sitting versus standing naturally remains unknown. METHODS: Metabolic requirements were quantified via indirect calorimetry from expired gases in 46 healthy men and women (age 27±12 y, mass 79.3±14.7 kg, body mass index 24.7±3.1 kg·m-2, waist:hip 0.81±0.06) under basal conditions (i.e. resting metabolic rate; RMR) and then, in a randomized and counterbalanced sequence, during lying, sitting and standing. Critically, no restrictions were placed on natural/spontaneous bodily movements (i.e. fidgeting) to reveal the fundamental contrast between sitting and standing in situ whilst maintaining a comfortable posture. RESULTS: The mean [95% CI] increment in energy expenditure was 0.18 [0.06 to 0.31] kJ⋅min-1 from RMR to lying, 0.15 [0.03 to 0.27] kJ⋅min-1 from lying to sitting and 0.65 [0.53 to 0.77] kJ⋅min-1 from sitting to standing. The observed energy cost of each posture above basal metabolic requirements exhibited marked inter-individual variance, which was inversely correlated with resting heart rate for all postures (r=-0.5 [-0.7 to -0.1]) and positively correlated with self-reported physical activity levels for lying (r=0.4 [0.1 to 0.7]) and standing (r=0.6 [0.3 to 0.8]). CONCLUSION: Interventions designed to reduce sitting typically encourage 30-120 min⋅d-1 more standing in situ (rather than perambulation), so the 12 % difference from sitting to standing reported here does not represent an effective strategy for the treatment of obesity but may have a role in primary prevention by maintaining long-term energy balance.
Background: Long COVID and similarly presenting vaccine injuries currently have no recognised clinical treatment. As such, many patients have resorted to self-experiments with a variety of therapeutics. One such therapeutic is venesection. Aim: To test whether venesection could reliably improve symptom burden. Methods: This was a n-of-1 blinded randomised controlled self-experiment. Sham or real venesection was conducted (n = 4 trials in total), with symptom scores taken pre- and post-intervention. Results: Based on symptom relief post-venesection, it was predicted that trials 1 and 3 were real venesection, and trials 2 and 4 were sham venesection. Unblinding revealed trials 1, 2, and 4 were real venesection, and trial 3 was sham venesection, thereby rejecting the hypothesis that venesection would improve symptoms. Δ pre- to immediately post-intervention of the venesection trial for sum of symptom scores was -18 ± 7 for venesection and -26 for sham, and for the variable “overall roughness” was +1 ± 2 for venesection and +3 for sham. Δ pre- to 24-h post-intervention of the venesection trial for sum of symptom scores was -15 ± 26 for venesection and -21 for sham, and for the variable “overall roughness” was -0.5 ± 2 for venesection and -1 for sham.Conclusion: In this n-of-1 self-experiment, symptomatic improvement was not predicted by true venesection. The results seen could be due to natural circadian fluctuations of the self-experimenter’s symptoms (i.e. unrelated to venesection) and/or their own expectation effects. Whether this is an effective intervention in other patients requires testing, and this study provides proof-of-principle that sham venesection is feasible.
Prolonged sitting is a major health concern, targeted via government policy and the proliferation of height-adjustable workstations and wearable technologies to encourage standing. Such interventions have the potential to influence energy balance and thus facilitate effective management of body/fat mass. It is therefore remarkable that the energy cost of sitting versus standing naturally remains unknown.Metabolic requirements were quantified via indirect calorimetry from expired gases in 46 healthy men and women (age, 27 ± 12 yr; mass, 79.3 ± 14.7 kg; body mass index, 24.7 ± 3.1 kg·m, waist/hip, 0.81 ± 0.06) under basal conditions (i.e., resting metabolic rate) and then, in a randomized and counterbalanced sequence, during lying, sitting and standing. Critically, no restrictions were placed on natural/spontaneous bodily movements (i.e., fidgeting) to reveal the fundamental contrast between sitting and standing in situ while maintaining a comfortable posture.The mean (95% confidence interval [CI]) increment in energy expenditure was 0.18 (95% CI, 0.06-0.31 kJ·min) from resting metabolic rate to lying was 0.15 (95% CI, 0.03-0.27 kJ·min) from lying to sitting and 0.65 (95% CI, 0.53-0.77 kJ·min) from sitting to standing. An ancillary observation was that the energy cost of each posture above basal metabolic requirements exhibited marked interindividual variance, which was inversely correlated with resting heart rate for all postures (r = -0.5; -0.7 to -0.1) and positively correlated with self-reported physical activity levels for lying (r = 0.4; 0.1 to 0.7) and standing (r = 0.6; 0.3-0.8).Interventions designed to reduce sitting typically encourage 30 to 120 min·d more standing in situ (rather than perambulation), so the 12% difference from sitting to standing reported here does not represent an effective strategy for the treatment of obesity (i.e., weight loss) but could potentially attenuate any continued escalation of the ongoing obesity epidemic at a population level.
Background: Variability in sweet preference between people is well established, with those who have a high preference colloquially identified as having a sweet tooth. Although characteristics have been described demonstrating key differences between those with and without a sweet tooth (such as differences in body mass index), it is less clear whether sweet preference moderates appetite and health responses to stimuli of different sweetness levels.Objective: To explore appetite and health responses to a sugar-sweetened (SWEET) and unsweetened (PLAIN) porridge-based breakfast, according to whether participants identified as having a sweet tooth or not. Methods: Secondary data analysis of a previously published randomised crossover trial in which n = 29 participants consumed an isocaloric PLAIN (~8 g sugar) and SWEET (~32 g sugar) porridge-based breakfast for three weeks each. Fasted pre- and post-intervention measures included blood biomarkers of health and appetite hormones, anthropometrics and metabolic rate, and a series of questionnaires assessing psychological appetite/approach to food. During each three week intervention, four days of lifestyle monitoring were conducted on days 1-4 and days 15-18, involving weighed food diaries, physical activity measurements (ActiHeart™), and visual analogue scales of appetite across the day. After study completion, participants were asked whether they believed they had a sweet tooth or not; n = 27 responded and were included in these analyses. Analyses were exploratory with no significance testing or a priori hypothesis. Results: 16 participants reported not having a sweet tooth. Average body mass index was higher in those without a sweet tooth (25.9 ± 6.0 kg/m2 versus 24.4 ± 4.3 kg/m2 for those with a sweet tooth), but waist-to-hip ratio was lower. Having a sweet tooth was associated with a higher desire for sweet across the day during both interventions compared to those without a sweet tooth, but also lower sugar intake. Sweet sensory-specific satiety was achieved in both groups post-breakfast during SWEET, whilst savoury sensory-specific satiety was achieved post-breakfast after both PLAIN and SWEET. Fasting plasma fibroblast growth factor 21 was higher in those with a sweet tooth, whilst fasting glucagon-like peptide-1 increased pre- to post-PLAIN (Δ 6.2, 95 % CI 1.1, 11.4 pmol∙L-1), but was otherwise similar across interventions and between groups. Those without a sweet tooth reduced their energy intake from week 1 to week 3 of PLAIN (Δ -152, 95 % CI -349, 45 kcal/d), whereas those with a sweet tooth (less reliably) increased their energy intake (Δ 131, 95 % CI -131, 395 kcal/d). No changes in energy intake were noted during SWEET. Physical activity energy expenditure largely remained consistent between groups and across interventions, though those without a sweet tooth increased their physical activity energy expenditure from week 1 to week 3 of SWEET (Δ 166, 95 % CI -8, 241 kcal/d).Conclusion: Having a sweet tooth was associated with distinct characteristics, such as lower body mass index and higher fasted plasma fibroblast growth factor 21 concentrations. Sweet preference may moderate biopsychological metabolic and appetitive responses to savoury or sweet primes. Due to the small sample size and other methodological features of these analyses, future work should establish the causality of these findings, and may need to consider sweet preference a priori when designing health and appetite research relating to sweetness.
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