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Infection control measures to prevent viral and bacterial infection spread are critical to maintaining a healthy environment. Pathogens such as viruses and pyogenic bacteria can cause infectious complications. Viruses such as SARS-CoV-2 are known to spread through the aerosol route and on fomite surfaces, lasting for a prolonged time in the environment. Developing technologies to mitigate the spread of pathogens through airborne routes and on surfaces is critical, especially for patients at high risk for infectious complications. Multifunctional coatings with a broad capacity to bind pathogens that result in inactivation can disrupt infectious spread through aerosol and inanimate surface spread. This study uses C-POLAR, a proprietary cationic, polyamine, organic polymer with a charged, dielectric property coated onto air filtration material and textiles. Using both SARS-CoV-2 live viral particles and bovine coronavirus models, C-POLAR-treated material shows a dramatic 2-log reduction in circulating viral inoculum. This reduction is consistent in a static room model, indicating simple airflow through a static C-POLAR hanging can capture significant airborne particles. Finally, Gram-positive and Gram-negative bacteria are applied to C-POLAR textiles using a viability indicator to demonstrate eradication on fomite surfaces. These data suggest that a cationic polymer surface can capture and eradicate human pathogens, potentially interrupting the infectious spread for a more resilient environment. IMPORTANCE: Infection control is critical for maintaining a healthy home, work, and hospital environment. We test a cationic polymer capable of capturing and eradicating viral and bacterial pathogens by applying the polymer to the air filtration material and textiles. The data suggest that the simple addition of cationic material can result in the improvement of an infectious resilient environment against viral and bacterial pathogens.
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BACKGROUND: Although the efficacy of interval training for improving body composition has been summarized in an increasing number of systematic reviews in recent years, discrepancies in review findings and conclusions have been observed. OBJECTIVE: This study aims to synthesize the available evidence on the efficacy of interval training compared with moderate-intensity continuous training (MICT) and nonexercise control (CON) in reducing body adiposity in apparently healthy adults. METHODS: An umbrella review with meta-analysis was performed. A systematic search was conducted in seven databases (MEDLINE, EMBASE, Cochrane Database, CINAHL, Scopus, SPORTDiscus, and Web of Science) up to October 2023. Systematic reviews with meta-analyses of randomized controlled trials (RCTs) comparing interval training and MICT/CON were included. Literature selection, data extraction, and methodological quality assessment (AMSTAR-2) were conducted independently by two reviewers. Meta-analyses were performed using a random-effects model. Subgroup analyses were conducted based on the type of interval training [high-intensity interval training (HIIT) and sprint interval training (SIT)], intervention duration, body mass index, exercise modality, and volume of HIIT protocols. RESULTS: Sixteen systematic reviews, including 79 RCTs and 2474 unique participants, met the inclusion criteria. Most systematic reviews had a critically low (n = 6) or low (n = 6) AMSTAR-2 score. Interval training demonstrated significantly greater reductions in total body fat percent (BF%) compared with MICT [weighted mean difference (WMD) of - 0.77%; 95% confidence interval (CI) - 1.12 to - 0.32%] and CON (WMD of - 1.50%; 95% CI - 2.40 to - 0.58%). Significant reductions in fat mass, visceral adipose tissue, subcutaneous abdominal fat, and android abdominal fat were also observed following interval training compared to CON. Subgroup analyses indicated that both HIIT and SIT resulted in superior BF% loss than MICT. These benefits appeared to be more prominent in individuals with overweight/obesity and longer duration interventions (≥ 12 weeks), as well as in protocols using cycling as a modality and low-volume HIIT (i.e., < 15 min of high-intensity exercise per session). CONCLUSIONS: This novel umbrella review with large-scale meta-analysis provides an updated synthesis of evidence with implications for physical activity guideline recommendations. The findings support interval training as a viable exercise strategy for reducing adiposity in the general population.
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The effects of exogenous ketones on appetite and food intake remain elusive, especially for people with type 2 diabetes (T2D). This study aimed to determine whether acute ingestion of an oral ketone monoester supplement (KME) affected appetite sensations, prospective food consumption and intake in T2D. Results showed that acute KME ingestion did not significantly alter appetite scores. However, there was a tendency for lower energy intake during an ad libitum meal 3 h following ketone ingestion compared to non-energetic placebo. Further research is warranted to understand the long-term effects of exogenous ketones for energy and macronutrient intake in T2D.
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Circulating interleukin (IL)-6 and IL-10 concentrations are widely used to evaluate the anti-inflammatory effects of exercise but do not capture cytokine action at the cellular level. Whether and how acute exercise impacts anti-inflammatory cytokine action in humans is unknown. To determine how exercise intensity and pattern impact IL-6 and IL-10 action in blood leukocytes, 16 active adults (eight males/eight females; age: 30 ± 3 years; body mass index: 22.8 ± 2.3 kg/m2; V Ì O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ : 51 ± 6 mL/kg/min) completed a no-exercise control condition (CTL) or isocaloric bouts of cycling performed below (moderate continuous exercise; MCE) or above (heavy continuous or heavy intermittent exercise; HCE or HIE, respectively) lactate threshold. Venous blood (before, after, 30 min after and 90 min after exercise) was analysed for immune cell subpopulations, plasma cytokine concentrations, anti-inflammatory cytokine action and monocyte phenotype. Exercise induced rapid leukocytosis (P < 0.001) and increased plasma IL-6 (P < 0.001), IL-10 (P = 0.0145) and tumour necrosis factor-⺠(TNF-âº) (P = 0.0338) concentrations in an intensity-dependent manner (HCE and/or HIE vs. CTL). These systemic changes coincided with a diminished ability of IL-10/6 to phosphorylate STAT3 (P < 0.001) and inhibit TNF-⺠secretion (P = 0.0238) in blood leukocytes following HCE and HIE. Monocyte polarization experiments revealed lower CD80 [MCE (P = 0.0933) and HIE (P = 0.0187) vs. CTL] and a tendency for higher CD163 expression (HCE vs. CTL, P = 0.0985), suggesting that hyporesponsiveness to anti-inflammatory cytokine action does not impede the ability of exercise to promote an anti-inflammatory monocyte phenotype. These findings provide novel insights into the immunomodulatory effects of exercise in humans and highlight the importance of directly measuring cellular cytokine action when evaluating the anti-inflammatory effects of exercise. KEY POINTS: Circulating cytokine concentrations are frequently used to evaluate the anti-inflammatory effects of exercise but may not capture changes in cytokine action occurring at the cellular level. We directly assessed anti-inflammatory cytokine action - measured using a combination of intracellular signalling and cytokine secretion ex vivo - in distinct immune cell subpopulations after acute calorie-matched exercise bouts differing in intensity and pattern. Anti-inflammatory cytokine action was blunted following higher intensity exercise despite corresponding increases in circulating cytokine concentrations and immune cell counts. Changes in cytokine action were not explained by changes in cytokine receptor expression on circulating immune cells. Our findings provide new insights into the immunomodulatory effects of exercise in humans and highlight the importance of directly measuring cellular cytokine action when evaluating the anti-inflammatory effects of exercise.
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Exercício Físico , Interleucina-10 , Leucócitos , Humanos , Masculino , Adulto , Feminino , Exercício Físico/fisiologia , Leucócitos/metabolismo , Leucócitos/fisiologia , Interleucina-10/sangue , Interleucina-10/metabolismo , Citocinas/metabolismo , Citocinas/sangue , Interleucina-6/sangue , Interleucina-6/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Substantial weight loss in people living with type 2 diabetes (T2D) can reduce the need for glucose-lowering medications while concurrently lowering glycemia below the diagnostic threshold for the disease. Furthermore, weight-loss interventions have also been demonstrated to improve aspects of underlying T2D pathophysiology related to ectopic fat in the liver and pancreatic beta-cell function. As such, the purpose of this secondary analysis was to explore the extent to which a low-carbohydrate and energy-restricted (LCER) diet intervention improves markers of beta-cell stress/function, liver fat accumulation, and metabolic related liver function in people with type 2 diabetes. METHODS: We conducted secondary analyses of blood samples from a larger pragmatic community-based parallel-group randomized controlled trial involving a 12-week pharmacist implemented LCER diet (Pharm-TCR: <50 g carbohydrates; ~850-1100 kcal/day; n = 20) versus treatment-as-usual (TAU; n = 16). Participants were people with T2D, using ≥ 1 glucose-lowering medication, and a body mass index of ≥ 30 kg/m2. Main outcomes were C-peptide to proinsulin ratio, circulating microRNA 375 (miR375), homeostatic model assessment (HOMA) beta-cell function (B), fatty liver index (FLI), hepatic steatosis index (HSI), HOMA insulin resistance (IR), and circulating fetuin-A and fibroblast growth factor 21 (FGF21). Data were analysed using linear regression with baseline as a covariate. RESULTS: There was no observed change in miR375 (p = 0.42), C-peptide to proinsulin ratio (p = 0.17) or HOMA B (p = 0.15). FLI and HSI were reduced by -25.1 (p < 0.0001) and - 4.9 (p < 0.0001), respectively. HOMA IR was reduced by -46.5% (p = 0.011). FGF21 was reduced by -161.2pg/mL (p = 0.035) with a similar tendency found for fetuin-A (mean difference: -16.7ng/mL; p = 0.11). These improvements in markers of hepatic function were accompanied by reductions in circulating metabolites linked to hepatic insulin resistance (e.g., diacylglycerols, ceramides) in the Pharm TCR group. CONCLUSIONS: The Pharm-TCR intervention did not improve fasting indices of beta-cell stress; however, markers of liver fat accumulation and and liver function were improved, suggesting that a LCER diet can improve some aspects of the underlying pathophysiology of T2D. TRIAL REGISTRATION: Clinicaltrials.gov (NCT03181165).
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Exercício Físico , Carga de Trabalho , Humanos , Esforço Físico , Consumo de Oxigênio , Teste de Esforço , Frequência CardíacaRESUMO
The aims of this study were (1) to determine how stair-climbing-based exercise snacks (ES) compared to moderate-intensity continuous training (MICT) for improving cardiorespiratory fitness (CRF), and (2) to explore whether ES could improve maximal fat oxidation rate (MFO) in inactive adults. Healthy, young, inactive adults (n: 42, age: 21.6 ± 2.3 years, BMI: 22.5 ± 3.6 kg·m-2, peak oxygen uptake (VO2peak): 33.6 ± 6.3 mL·kg-1·min-1) were randomly assigned to ES, MICT, or Control. ES (n = 14) and MICT (n = 13) groups performed three sessions per week over 6 weeks, while the control group (n = 15) maintained their habitual lifestyle. ES involved 3 × 30 s "all-out" stair-climbing (6 flight, 126 steps, and 18.9 m total height) bouts separated by >1 h rest, and MICT involved 40 min × 60%-70% HRmax stationary cycling. A significant group × time interaction was found for relative VO2peak (p < 0.05) with ES significantly increasing by 7% compared to baseline (MD = 2.5 mL·kg-1·min-1 (95% CI = 1.2, 3.7), Cohen's d = 0.44), while MICT had no significant effects (MD = 1.0 mL·kg-1·min-1 (-1.1, 3.2), Cohen's d = 0.17), and Control experienced a significant decrease (MD = -1.7 mL·kg-1·min-1 (-2.9, -0.4), Cohen's d = 0.26). MFO was unchanged among the three groups (group × time interaction, p > 0.05 for all). Stair climbing-based ES are a time-efficient alternative to MICT for improving CRF among inactive adults, but the tested ES intervention appears to have limited potential to increase MFO.
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Aptidão Cardiorrespiratória , Exercício Físico , Oxirredução , Consumo de Oxigênio , Lanches , Humanos , Masculino , Aptidão Cardiorrespiratória/fisiologia , Feminino , Adulto Jovem , Consumo de Oxigênio/fisiologia , Exercício Físico/fisiologia , Adulto , Subida de Escada/fisiologia , Comportamento SedentárioRESUMO
BACKGROUND: Neglect of vaccination needs among adults results in a needless burden of hospitalization, suffering, and death. America's community pharmacists deliver a substantial portion of adult vaccinations, yet many Americans still have unmet vaccination needs. OBJECTIVES: This study evaluated rates of vaccine contraindications, acceptance, and willingness to be vaccinated among ambulatory adults. PRACTICE DESCRIPTION: This was a prospective, multisite, multistate, observational study conducted in three waves between October 2021 and August 2023. PRACTICE INNOVATION: Pharmacists conducted comprehensive vaccination need assessments. EVALUATION METHODS: The primary outcomes were numbers of vaccination needs per participant and vaccinations administered, scheduled, or declined. RESULTS: Pharmacists identified a mean of 1.8-2.2 unmet vaccination needs per adult assessed, more than in pilot studies. Participants had already received 61%-74% of vaccinations recommended for them hence 26%-39% of needs were unmet at baseline. The leading vaccination needs were COVID-19, influenza, zoster, tetanus-containing, and pneumococcal vaccines. From a baseline mean of 59.1% for these five vaccinations, pharmacists increased the mean percentage vaccinated to 73.2%. When an option for scheduling future vaccination was added to the process, declinations dropped from 46%-18%. CONCLUSION: This study provides insight into adult vaccine acceptance, willingness, and declination behaviors not described elsewhere. Offering options for future vaccination reduced declination rates. Pharmacists resolved substantial proportions of adult vaccination needs. The signal that apportioning adult vaccines needed, but not received on day of assessment, across several months could help resolve unmet vaccination needs warrants additional research, especially with the rising number of vaccines recommended for adults.
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Farmacêuticos , Vacinação , Humanos , Farmacêuticos/estatística & dados numéricos , Estudos Prospectivos , Feminino , Masculino , Vacinação/estatística & dados numéricos , Adulto , Pessoa de Meia-Idade , Serviços Comunitários de Farmácia/estatística & dados numéricos , Idoso , Papel Profissional , Estados Unidos , Avaliação das NecessidadesRESUMO
AIMS/HYPOTHESIS: The aim of the present study was to conduct a randomised, placebo-controlled, double-blind, crossover trial to determine whether pre-meal ketone monoester ingestion reduces postprandial glucose concentrations in individuals with type 2 diabetes. METHODS: In this double-blind, placebo-controlled, crossover design study, ten participants with type 2 diabetes (age 59±1.7 years, 50% female, BMI 32±1 kg/m2, HbA1c 54±2 mmol/mol [7.1±0.2%]) were randomised using computer-generated random numbers. The study took place at the Nutritional Physiology Research Unit, University of Exeter, Exeter, UK. Using a dual-glucose tracer approach, we assessed glucose kinetics after the ingestion of a 0.5 g/kg body mass ketone monoester (KME) or a taste-matched non-caloric placebo before a mixed-meal tolerance test. The primary outcome measure was endogenous glucose production. Secondary outcome measures were total glucose appearance rate and exogenous glucose appearance rate, glucose disappearance rate, blood glucose, serum insulin, ß-OHB and NEFA levels, and energy expenditure. RESULTS: Data for all ten participants were analysed. KME ingestion increased mean ± SEM plasma beta-hydroxybutyrate from 0.3±0.03 mmol/l to a peak of 4.3±1.2 mmol/l while reducing 2 h postprandial glucose concentrations by ~18% and 4 h postprandial glucose concentrations by ~12%, predominately as a result of a 28% decrease in the 2 h rate of glucose appearance following meal ingestion (all p<0.05). The reduction in blood glucose concentrations was associated with suppressed plasma NEFA concentrations after KME ingestion, with no difference in plasma insulin concentrations between the control and KME conditions. Postprandial endogenous glucose production was unaffected by KME ingestion (mean ± SEM 0.76±0.15 and 0.88±0.10 mg kg-1 min-1 for the control and KME, respectively). No adverse effects of KME ingestion were observed. CONCLUSIONS/INTERPRETATION: KME ingestion appears to delay glucose absorption in adults with type 2 diabetes, thereby reducing postprandial glucose concentrations. Future work to explore the therapeutic potential of KME supplementation in type 2 diabetes is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT05518448. FUNDING: This project was supported by a Canadian Institutes of Health Research (CIHR) Project Grant (PJT-169116) and a Natural Sciences and Engineering Research Council (NSERC) Discovery Grant (RGPIN-2019-05204) awarded to JPL and an Exeter-UBCO Sports Health Science Fund Project Grant awarded to FBS and JPL.
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Glicemia , Estudos Cross-Over , Diabetes Mellitus Tipo 2 , Cetonas , Período Pós-Prandial , Humanos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Pessoa de Meia-Idade , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Masculino , Método Duplo-Cego , Cetonas/sangue , Ácido 3-Hidroxibutírico/sangue , Insulina/sangue , BebidasRESUMO
Pre-clinical and cell culture evidence supports the role of the ketone beta-hydroxybutyrate (BHB) as an immunomodulatory molecule that may inhibit inflammatory signalling involved in several chronic diseases such as type 2 diabetes (T2D), but studies in humans are lacking. Therefore, we investigated the anti-inflammatory effect of BHB in humans across three clinical trials. To investigate if BHB suppressed pro-inflammatory cytokine secretion, we treated LPS-stimulated leukocytes from overnight-fasted adults at risk for T2D with BHB (Study 1). Next (Study 2), we investigated if exogenously raising BHB acutely in vivo by ketone monoester supplementation (KME) in adults with T2D would suppress pro-inflammatory plasma cytokines. In Study 3, we investigated the effect of BHB on inflammation via ex vivo treatment of LPS-stimulated leukocytes with BHB and in vivo thrice-daily pre-meal KME for 14 days in adults with T2D. Ex vivo treatment with BHB suppressed LPS-stimulated IL-1ß, TNF-α, and IL-6 secretion and increased IL-1RA and IL-10 (Study 1). Plasma IL-10 increased by 90 min following ingestion of a single dose of KME in T2D, which corresponded to peak blood BHB (Study 2). Finally, 14 days of thrice-daily KME ingestion did not significantly alter plasma cytokines or leukocyte subsets including monocyte and T-cell polarization (Study 3). However, direct treatment of leukocytes with BHB modulated TNF-α, IL-1ß, IFN-γ, and MCP-1 secretion in a time- and glucose-dependent manner (Study 3). Therefore, BHB appears to be anti-inflammatory in T2D, but this effect is transient and is modulated by the presence of disease, glycaemia, and exposure time.
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Diabetes Mellitus Tipo 2 , Interleucina-10 , Adulto , Humanos , Ácido 3-Hidroxibutírico/farmacologia , Ácido 3-Hidroxibutírico/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cetonas/uso terapêutico , Fator de Necrose Tumoral alfa , Lipopolissacarídeos , Inflamação/tratamento farmacológico , Citocinas , Anti-Inflamatórios/uso terapêutico , Interleucina-1beta , ImunidadeRESUMO
In the workplace, people are often sedentary for prolonged time and do not regularly engage in physical activity-two factors independently linked to premature morbidity and mortality. This study aimed to determine the receptivity of incorporating practical stair-climbing "exercise snacks" (Snacks; three isolated bouts of ascending 53-60 stairs performed sporadically throughout the day) into workplace settings compared to more traditional high-intensity interval training (HIIT; performed as three bouts of 53-60 stairs within a structured HIIT workout) and to explore if these exercise strategies could influence sedentary and physical activity behaviour. Fourteen participants (12 women; Mage = 38.9 ± 10.2 years) completed two supervised exercise trials (Snacks and HIIT) followed by 1 week participating in either form of exercise in their workplace. Ratings of perceived exertion (RPE), affective valence, enjoyment, and self-efficacy were measured at the supervised exercise sessions. During the follow-up period, sedentary behaviour and physical activity were measured with an accelerometer. Affective valence was more positive (p = 0.03; η2 p = 0.21) and there was a lower rise in RPE (p = 0.01; η2 p = 0.29) during Snacks than HIIT. Post-exercise enjoyment of, and self-efficacy towards, Snacks and HIIT were high and similar (ps > 0.05). After the supervised trials, 10/14 of the participants preferred Snacks and 4/14 preferred HIIT (p = 0.18). On days when participants chose to perform either exercise modality, the average number of sit-to-stands in a 24 h period was increased (48.3 ± 8.7 to 52.8 ± 7.8; p = 0.03; Hedge's g = 0.73) and moderate-to-vigorous physical activity tended to increase (21.9 ± 18.2 to 38.1 ± 22.1 min; p = 0.06; Hedge's g = 0.60) compared to days when they chose not to exercise. Stair-climbing exercise snacks may be an attractive approach to implement in the workplace setting and has potential to positively impact sedentary behaviour and physical activity metrics.
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Treinamento Intervalado de Alta Intensidade , Lanches , Humanos , Feminino , Exercício Físico/psicologia , Treinamento Intervalado de Alta Intensidade/psicologia , Prazer , Local de TrabalhoRESUMO
The present meta-analysis aimed to assess the effects of low-volume high-intensity interval training (LV-HIIT; i.e., ≤5 min high-intensity exercise within a ≤15 min session) on cardiometabolic health and body composition. A systematic search was performed in accordance with PRISMA guidelines to assess the effect of LV-HIIT on cardiometabolic health and body composition. Twenty-one studies (moderate to high quality) with a total of 849 participants were included in this meta-analysis. LV-HIIT increased cardiorespiratory fitness (CRF, SMD = 1.19 [0.87, 1.50]) while lowering systolic blood pressure (SMD = -1.44 [-1.68, -1.20]), diastolic blood pressure (SMD = -1.51 [-1.75, -1.27]), mean arterial pressure (SMD = -1.55 [-1.80, -1.30]), MetS z-score (SMD = -0.76 [-1.02, -0.49]), fat mass (kg) (SMD = -0.22 [-0.44, 0.00]), fat mass (%) (SMD = -0.22 [-0.41, -0.02]), and waist circumference (SMD = -0.53 [-0.75, -0.31]) compared to untrained control (CONTROL). Despite a total time-commitment of LV-HIIT of only 14%-47% and 45%-94% compared to moderate-intensity continuous training and HV-HIIT, respectively, there were no statistically significant differences observed for any outcomes in comparisons between LV-HIIT and moderate-intensity continuous training (MICT) or high-volume HIIT. Significant inverse dose-responses were observed between the change in CRF with LV-HIIT and sprint repetitions (ß = -0.52 [-0.76, -0.28]), high-intensity duration (ß = -0.21 [-0.39, -0.02]), and total duration (ß = -0.19 [-0.36, -0.02]), while higher intensity significantly improved CRF gains. LV-HIIT can improve cardiometabolic health and body composition and represent a time-efficient alternative to MICT and HV-HIIT. Performing LV-HIIT at a higher intensity drives higher CRF gains. More repetitions, longer time at high intensity, and total session duration did not augment gains in CRF.
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Aptidão Cardiorrespiratória , Doenças Cardiovasculares , Treinamento Intervalado de Alta Intensidade , Humanos , Composição Corporal , Exercício FísicoRESUMO
Overactivation of the NLRP3 inflammasome is implicated in chronic low-grade inflammation associated with various disease states, including obesity, type 2 diabetes, atherosclerosis, Alzheimer's disease, and Parkinson's disease. Emerging evidence, mostly from cell and animal models of disease, supports a role for ketosis in general, and the main circulating ketone body beta-hydroxybutyrate (BHB) in particular, in reducing NLRP3 inflammasome activation to improve chronic inflammation. As a result, interventions that can induce ketosis (e.g., fasting, intermittent fasting, time-restricted feeding/eating, very low-carbohydrate high-fat ketogenic diets) and/or increase circulating BHB (e.g., exogenous ketone supplementation) have garnered increasing interest for their therapeutic potential. The purpose of the present review is to summarize our current understanding of the literature on how ketogenic interventions impact the NLRP3 inflammasome across human, rodent and cell models. Overall, there is convincing evidence that ketogenic interventions, likely acting through multiple interacting mechanisms in a cell-, disease- and context-specific manner, can reduce NLRP3 inflammasome activation. The evidence supports a direct effect of BHB, although it is important to consider the myriad of other metabolic responses to fasting or ketogenic diet interventions (e.g., elevated lipolysis, low insulin, stable glucose, negative energy balance) that may also impact innate immune responses. Future research is needed to translate promising findings from discovery science to clinical application.
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Diabetes Mellitus Tipo 2 , Dieta Cetogênica , Cetose , Animais , Humanos , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Corpos Cetônicos , Cetonas , Jejum , Ácido 3-Hidroxibutírico/metabolismo , Ácido 3-Hidroxibutírico/farmacologia , InflamaçãoRESUMO
Acute ingestion of the exogenous ketone monoester supplement [(R)-3-hydroxybutyl-(R)-3-hydroxybutyrate] lowers blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, it is unknown how acute or repeated ingestion of exogenous ketones affects blood glucose control in individuals with type 2 diabetes (T2D). We conducted two randomized, counterbalanced, double-blind, placebo-controlled crossover trials to determine if 1) acute exogenous ketone monoester (0.3 g/kg body mass; N = 18) or 2) 14-day thrice daily premeal exogenous ketone monoester (15 g; N = 15) supplementation could lower blood glucose in individuals living with T2D. A single dose of the ketone monoester supplement elevated blood ß-OHB to â¼2 mM. There were no differences in the primary outcomes of plasma glucose concentration (acutely) or serum fructosamine (glycemic control across 14 days) between conditions. Ketone monoester ingestion acutely increased insulin and lowered nonesterified fatty acid concentrations; plasma metabolomics confirmed a reduction in multiple free fatty acids species and select gluconeogenic amino acids. In contrast, no changes were observed in fasting metabolic outcomes following 14 days of supplementation. In the context of these randomized controlled trials, acute or repeated ketone monoester ingestion in adults with T2D did not lower blood glucose when consumed acutely in a fasted state and did not improve glycemic control following thrice daily premeal ingestion across 14 days. Future studies exploring the mechanistic basis for the (lack of) glucose-lowering effect of exogenous ketone supplementation in T2D and other populations are warranted.NEW & NOTEWORTHY Exogenous ketone supplements can acutely lower blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, the effect of exogenous ketones on glucose metabolism in adults with type 2 diabetes has not been investigated in a controlled setting. In adults with type 2 diabetes, ketone monoester ingestion did not lower blood glucose acutely in a fasted state and did not improve glycemic control across thrice daily premeal ingestion across 14 days.
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Diabetes Mellitus Tipo 2 , Cetonas , Humanos , Adulto , Cetonas/farmacologia , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Controle Glicêmico , Ácido 3-Hidroxibutírico , Ensaios Clínicos Controlados Aleatórios como Assunto , Suplementos NutricionaisRESUMO
Exogenous ketone monoesters can raise blood ß-OHB and lower glucose without other nutritional modifications or invasive procedures. However, unpleasant taste and potential gastrointestinal discomfort may make adherence to supplementation challenging. Two novel ketone supplements promise an improved consumer experience but differ in their chemical properties; it is currently unknown how these affect blood ß-OHB and blood glucose compared to the ketone monoester. In a double-blind randomized cross-over pilot study, N=12 healthy individuals (29 ± 5 years, BMI = 25 ± 4 kg/m2, 42% female) participated in three experimental trials with a different ketone supplement providing 10 grams of active ingredient in each; (i) the monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, (ii) D-ß-hydroxybutyric acid with R-1,3-butanediol, and (iii) R-1,3-butanediol. Blood ß-OHB and glucose were measured via finger prick capillary blood samples at baseline and across 240 minutes post-supplementation. Supplement acceptability, hunger, and gastrointestinal distress were assessed via questionnaires. ß-OHB was elevated compared to baseline in all conditions. Total and incremental area under the curve (p < 0.05) and peak ß-OHB (p < 0.001) differed between conditions with highest values seen in the ketone monoester condition. Blood glucose was reduced after consumption of each supplement, with no differences in total and incremental area under the curve across supplements. Supplement acceptability was greatest for D-ß-hydroxybutyric acid with R-1,3-butanediol, with no effect on hunger or evidence of gastrointestinal distress across all supplements. All ketone supplements tested raised ß-OHB with highest values seen after ketone monoester ingestion. Blood glucose was lowered similarly across the assessed time frame with all three supplements.
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Glicemia , Cetonas , Feminino , Humanos , Masculino , Ácido 3-Hidroxibutírico , Suplementos Nutricionais , Glucose , Projetos Piloto , Método Duplo-CegoRESUMO
Exogenous ketone supplements have been suggested to have potential cardiovascular benefits, but their overall effect on blood pressure is unclear. Our objective was to perform a systematic review and meta-analysis on the effects of exogenous ketone supplements on blood pressure (BP) and concomitant changes in resting heart rate (HR). Five databases were searched on January 27th, 2023, for randomized and non-randomized studies. A random-effects model meta-analysis was performed including all studies jointly and separately for acute and chronic ingestion of ketone supplements. Out of 4012 studies identified in the search, 4 acute and 6 chronic studies with n = 187 participants were included. Pooled results (n = 10) showed no change in systolic (SMD [95% CI]= -0.14 [-0.40; 0.11]; I2= 30%; p = 0.17) or diastolic BP (-0.12 [-0.30; 0.05]; I2= 0%; p = 0.69), with a potential tendency observed toward increased resting heart rate (0.17 [-0.14; 0.47]; I2= 40%; p = 0.10). Similar results for systolic and diastolic BP were observed when assessing separately the effect of acute and chronic ingestion of ketone supplements (p ≥ 0.33). Supplement dosage was found to modulate the increase in resting heart rate (0.019 ± 0.006; p = 0.013; R2=100%), suggesting that higher supplement doses lead to a higher resting heart rate. Based on currently available data, acute or prolonged ingestion of ketone supplements does not seem to modulate BP. However, a tendency for HR to increase after acute ingestion was observed, particularly with higher doses. Higher quality studies with appropriate standardized measurements are needed to confirm these results.
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Pressão Sanguínea , Suplementos Nutricionais , Frequência Cardíaca , Cetonas , Humanos , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Cetonas/administração & dosagem , Adulto , Feminino , Masculino , Pessoa de Meia-IdadeRESUMO
Background: Atrial Fibrillation (Afib) can lead to stroke and heart failure, and early detection of Afib is an effective method of preventing these life-threatening conditions. An estimated 2.7 million Americans are living with Afib1, a number that is expected to rise dramatically in the coming years. Methods: The aim of this demonstration project was to create an additional access point in the community at local pharmacies for Afib screening, detection, and referral to physicians for follow-up and initiation of evidence-based therapy when appropriate. This prospective research study was conducted with 14 community pharmacies across the US, in which a total of 650 patients were screened for Afib. Pharmacists conducted SAFEty Risk Assessments that consisted of completion of a Stroke Risk Scorecard and EKG determination utilizing AliveCor's KardiaMobile® 6L device. Results: In 552 (82.5%) of 669 total EKG readings, a "normal" rhythm was detected, and in 117 (17.5%) EKG readings an abnormal detection occurred. A total of 12 out of 650 patients (1.8%) received EKG readings of Afib, which is greater than double the expected prevalence of Afib in the US (0.81%), a statistically significant finding (p < 0.0001). Other notable findings included 42 (6.3%) EKG readings of Wide QRS, and 26 (3.9%) EKG readings of tachycardia. A total of 44 patients were referred to physicians for follow-up on their risk for Afib. Conclusions: Community pharmacies offer a unique, valuable access point for patients to receive Afib screenings. Pharmacists are well positioned to make a significant contribution in the cardiovascular health of their patients and increase the value of team-based health care.
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BACKGROUND: In-task affective responses to moderate-intensity continuous exercise training (MICT) have been shown to predict future physical activity behavior. However, limited research has investigated whether this affect-behavior relationship is similar for high-intensity interval training (HIIT) and whether it holds true over the longer term. This study aims to determine (1) if in-task affect during 2 weeks of supervised MICT and HIIT predicted changes to unsupervised moderate-to-vigorous physical activity (MVPA) behavior 12 months post-intervention and (2) if this predictive relationship was moderated by exercise type (MICT vs. HIIT). METHOD: Ninety-nine adults (69.7% female; 50.9 ± 9.4 years) who were low active and overweight were randomized to 2 weeks of exercise training of MICT (n = 52) or HIIT (n = 47), followed by 12 months of accelerometry-assessed free-living MVPA. RESULTS: The pooled moderation model was not significant, F(3, 94) = 2.54, p = .07 (R2 = 0.085), with a non-significant group by affect interaction (p = .06). The conditional effect for MICT was significant (B = 17.27, t = 2.17, p = .03), suggesting that 12-month change in MVPA increased by 17.27 min/week for every one-point increase in in-task affect. The conditional effect for HIIT was not significant (p = .85), suggesting that in-task affect was not predictive of 12-month change in MVPA. CONCLUSION: The current findings raise important questions about whether the affect-behavior relationship may vary depending on exercise type. For HIIT-based exercise in particular, additional psychological constructs beyond in-task affect should be considered when attempting to predict future physical activity behavior.
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Interval training is a simple concept that refers to repeated bouts of relatively hard work interspersed with recovery periods of easier work or rest. The method has been used by high-level athletes for over a century to improve performance in endurance-type sports and events such as middle- and long-distance running. The concept of interval training to improve health, including in a rehabilitative context or when practiced by individuals who are relatively inactive or deconditioned, has also been advanced for decades. An important issue that affects the interpretation and application of interval training is the lack of standardized terminology. This particularly relates to the classification of intensity. There is no common definition of the term "high-intensity interval training" (HIIT) despite its widespread use. We contend that in a performance context, HIIT can be characterized as intermittent exercise bouts performed above the heavy-intensity domain. This categorization of HIIT is primarily encompassed by the severe-intensity domain. It is demarcated by indicators that principally include the critical power or critical speed, or other indices, including the second lactate threshold, maximal lactate steady state, or lactate turnpoint. In a health context, we contend that HIIT can be characterized as intermittent exercise bouts performed above moderate intensity. This categorization of HIIT is primarily encompassed by the classification of vigorous intensity. It is demarcated by various indicators related to perceived exertion, oxygen uptake, or heart rate as defined in authoritative public health and exercise prescription guidelines. A particularly intense variant of HIIT commonly termed "sprint interval training" can be distinguished as repeated bouts performed with near-maximal to "all out" effort. This characterization coincides with the highest intensity classification identified in training zone models or exercise prescription guidelines, including the extreme-intensity domain, anaerobic speed reserve, or near-maximal to maximal intensity classification. HIIT is considered an essential training component for the enhancement of athletic performance, but the optimal intensity distribution and specific HIIT prescription for endurance athletes is unclear. HIIT is also a viable method to improve cardiorespiratory fitness and other health-related indices in people who are insufficiently active, including those with cardiometabolic diseases. Research is needed to clarify responses to different HIIT strategies using robust study designs that employ best practices. We offer a perspective on the topic of HIIT for performance and health, including a conceptual framework that builds on the work of others and outlines how the method can be defined and operationalized within each context.
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Desempenho Atlético , Treinamento Intervalado de Alta Intensidade , Humanos , Treinamento Intervalado de Alta Intensidade/métodos , Consumo de Oxigênio/fisiologia , Exercício Físico/fisiologia , Desempenho Atlético/fisiologia , Ácido LácticoRESUMO
Aim: This study aimed to evaluate if physical activity is associated with systemic and cellular immunometabolic responses, in young adults after mild-to-moderate COVID-19 infection. Methods: Mild- to- moderate post-COVID-19 patients (70.50 ± 43.10 days of diagnosis; age: 29.4 (21.9- 34.9) years; BMI: 25.5 ± 4.3 kg m2 n = 20) and healthy age-matched controls (age: 29.3 (21.2 - 32.6) years; BMI: 25.4 ± 4.7 kg m2; n = 20) were evaluated. Physical activity levels (PAL), body composition, dietary habits, muscular and pulmonary function, mental health, sleep quality, metabolic parameters, immune phenotypic characterization, stimulated whole blood and PBMC culture (cytokine production), mRNA, and mitochondrial respiration in PBMCs were evaluated. Results: The post-COVID-19 group exhibited lower levels of moderate to vigorous physical activity (MVPA) (p = 0.038); therefore, all study comparisons were performed with adjustment for MVPA. Post-COVID-19 impacted the pulmonary function (FEV1, FEV1%pred, FVC, and FVC %pred) compared with the control (p adjusted by MVPA (p adj) <0.05). Post-COVID-19 exhibited lower levels of serum IL-6 (p adj <0.01), whereas it showed higher serum IL-10, triglyceride, leptin, IgG, ACE activity, TNFRSF1A, and PGE2 (p adj <0.05) levels compared with controls. Post-COVID-19 presented a lower percentage of Treg cells (p adj = 0.03) and altered markers of lymphocyte activation and exhaustion (lower CD28 expression in CD8+ T cells (p adj = 0.014), whereas CD4+T cells showed higher PD1 expression (p adj = 0.037)) compared with the control group. Finally, post- COVID-19 presented an increased LPS-stimulated whole- blood IL-10 concentration (p adj <0.01). When exploring mitochondrial respiration and gene expression in PBMCs, we observed a higher LEAK state value (p adj <0.01), lower OXPHOS activity (complex I) (p adj = 0.04), and expression of the Rev-Erb-α clock mRNA after LPS stimulation in the post-COVID-19 patients than in the control (p adj <0.01). Mainly, PAL was associated with changes in IL-10, triglyceride, and leptin levels in the plasma of post-COVID-19 patients. PAL was also associated with modulation of the peripheral frequency of Treg cells and the expression of PD-1 in CD8+ T cells, although it abrogated the statistical effect in the analysis of TNF-α and IL-6 production by LPS- and PMA-stimulated PBMC of post-COVID-19 patients. Conclusion: Young adults after mild-to-moderate SARS-CoV-2 infection appeared to have lower physical activity levels, which can be associated with clinical and immunometabolic responses in a complex manner.