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Habitual daily intake of a sweet and fatty snack modulates reward processing in humans.
Edwin Thanarajah, S, DiFeliceantonio, AG, Albus, K, Kuzmanovic, B, Rigoux, L, Iglesias, S, Hanßen, R, Schlamann, M, Cornely, OA, Brüning, JC, et al
Cell metabolism. 2023;35(4):571-584.e6
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The prolific amount of sugar and fat in modern Western diets is regarded as a significant contributor to overeating and consequential weight gain. Dopamine, a neurotransmitter involved in learning and reward signalling, is also important in regulating food intake. Energy-dense foods, often high in both sugar and fat, stimulate pleasure-signalling dopamine to encourage eating, even if no more energy is needed. It is acknowledged that in many cases of obesity, the function of dopamine appears to be altered. Yet it is uncertain whether this was pre-existing to obesity, a result of obesity or whether it was re-shaped though exposure to high sugar and high-fat diets. To gain more insights, this study evaluated whether adding a high-fat/high-sugar (HF/HS) snack or a low-fat/low-sugar (LF/LS) snack to a regular diet could change the candidates liking for fat, their brain responses to likeable foods like fat and sugar and if it impacted on sensory associative learning. The randomised controlled study was conducted for 8-weeks and included 49 people of normal-weight. The candidates were also monitored for any changes in weight and body fat, insulin resistance, leptin levels, and blood fats, and all completed self-reported dietary intake forms. The findings demonstrated that repeated exposure to HF/HS food reduced the preference for low-fat foods and up-regulated the brain responses when anticipating and consuming such highly palatable, energy-dense foods. Beyond increased brain response to HF/HS food, HF/HS exposure also induced a general rewiring of the brain by enhancing new sensory associations and behavioural adaptations that were unrelated to food. Notably, these changes all occurred independent of weight gain or alterations in metabolic function, thus suggesting that repeated exposure to HF/HS foods can change the physiology in healthy weight individuals to reduce their liking of healthier foods whilst at the same time increasing the reward responses to more palatable HF/ HS foods. The authors highlighted this as a risk for overeating and weight gain, arguing that reducing the exposure to energy-dense HF/HS food items therefore is critical in the prevention and management of obesity.
Abstract
Western diets rich in fat and sugar promote excess calorie intake and weight gain; however, the underlying mechanisms are unclear. Despite a well-documented association between obesity and altered brain dopamine function, it remains elusive whether these alterations are (1) pre-existing, increasing the individual susceptibility to weight gain, (2) secondary to obesity, or (3) directly attributable to repeated exposure to western diet. To close this gap, we performed a randomized, controlled study (NCT05574660) with normal-weight participants exposed to a high-fat/high-sugar snack or a low-fat/low-sugar snack for 8 weeks in addition to their regular diet. The high-fat/high-sugar intervention decreased the preference for low-fat food while increasing brain response to food and associative learning independent of food cues or reward. These alterations were independent of changes in body weight and metabolic parameters, indicating a direct effect of high-fat, high-sugar foods on neurobehavioral adaptations that may increase the risk for overeating and weight gain.
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Late, but Not Early, Night Sleep Loss Compromises Neuroendocrine Appetite Regulation and the Desire for Food.
Meyhöfer, S, Chamorro, R, Hallschmid, M, Spyra, D, Klinsmann, N, Schultes, B, Lehnert, H, Meyhöfer, SM, Wilms, B
Nutrients. 2023;15(9)
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Sleep loss has become common in modern societies. In parallel, the prevalence of obesity and metabolic comorbidities, such as type 2 diabetes, are rising worldwide. The aim of this study was to investigate the impact of the specific timing of sleep loss compared to regular sleep on appetite regulation and desire for foods. This study was a randomised, balanced, crossover design on three conditions spaced at least three and at maximum five weeks apart. Fifteen healthy young male participants were included. All participants had a regular sleep–wake cycle during the last four weeks before the experiments, with a minimum of 7 hours sleep per night. Results showed that ‘late-night sleep loss’, but not ‘early-night sleep loss’, elevated ghrelin concentrations, as well as feelings of hunger and appetite, and desire for food during the subsequent morning. Leptin concentrations were not affected by acute sleep loss per se, nor timing of sleep loss. Authors conclude that their findings could be of clinical interest to healthcare practitioners working with sleep deprived individuals, regarding sleep hygiene and appropriate sleep recommendations.
Abstract
OBJECTIVE There is evidence that reduced sleep duration increases hunger, appetite, and food intake, leading to metabolic diseases, such as type 2 diabetes and obesity. However, the impact of sleep timing, irrespective of its duration and on the regulation of hunger and appetite, is less clear. We aimed to evaluate the impact of sleep loss during the late vs. early part of the night on the regulation of hunger, appetite, and desire for food. METHODS Fifteen normal-weight ([mean ± SEM] body-mass index: 23.3 ± 0.4 kg/m2) healthy men were studied in a randomized, balanced, crossover design, including two conditions of sleep loss, i.e., 4 h sleep during the first night-half ('late-night sleep loss'), 4 h sleep during the second night-half ('early-night sleep loss'), and a control condition with 8h sleep ('regular sleep'), respectively. Feelings of hunger and appetite were assessed through visual analogue scales, and plasma ghrelin and leptin were measured from blood samples taken before, during, and after night-time sleep. RESULTS Ghrelin and feelings of hunger and appetite, as well as the desire for food, were increased after 'late-night sleep loss', but not 'early-night sleep loss', whereas leptin remained unaffected by the timing of sleep loss. CONCLUSIONS Our data indicate that timing of sleep restriction modulates the effects of acute sleep loss on ghrelin and appetite regulation in healthy men. 'Late-night sleep loss' might be a risk factor for metabolic diseases, such as obesity and type 2 diabetes. Thereby, our findings highlight the metabolic relevance of chronobiological sleep timing.
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Dose-response relationship between weight loss and improvements in obstructive sleep apnea severity after a diet/lifestyle interventions: secondary analyses of the "MIMOSA" randomized clinical trial.
Georgoulis, M, Yiannakouris, N, Kechribari, I, Lamprou, K, Perraki, E, Vagiakis, E, Kontogianni, MD
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2022;18(5):1251-1261
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Obstructive sleep apnoea (OSA) represents one of the most common and serious sleep-related breathing disorders. Excess body weight has emerged as the strongest modifiable predictor of the onset and severity of OSA. The aim of this study was to explore the dose-response relationship between the degree of weight loss and improvements in OSA severity. This study is a secondary analysis of the Mediterranean diet/lifestyle Intervention for the Management of Obstructive Sleep Apnea (MIMOSA) study, which was designed as a single-centre, single-blind, parallel, randomised, controlled clinical trial. Results show that respiratory events and oximetry indices improved only in patients who lost weight and improvements were proportional to the degree of weight loss. Authors conclude that their findings indicate a dose-response relationship between the degree of weight loss and improvement in OSA severity and symptoms. However, further research is needed to gather more data on the optimal degree of weight loss and appropriate weight-loss interventions for managing the wide spectrum of OSA severity to guide clinical practice.
Expert Review
Conflicts of interest:
None
Take Home Message:
Important from a public health perspective:
- This study has confirmed that even a small degree of weight loss can have a beneficial effect on respiratory events and oxygen desaturation in moderate-to-severe OSA, but clinicians should preferably aim at a ≥ 5% weight loss, and ideally a ≥ 10% weight loss, to achieve clinically meaningful reductions in OSA severity.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
OSA represents one of the most common and serious sleep-related breathing disorders, with a high worldwide prevalence of almost 1 billion people. OSA has numerous well-established cardiometabolic consequences.
The authors highlight that weight loss is essential for obstructive sleep apnea (OSA) management. However, the optimal degree of weight loss for improving OSA severity or eliminating sleep-disordered breathing has not been extensively studied. The aim of this study was to explore the dose-response relationship between the degree of weight loss and improvements in OSA severity.
Methods
This is a secondary analysis of the Mediterranean diet/lifestyle Intervention for the Management of Obstructive Sleep Apnea (MIMOSA) study. This study was designed as a single-center, single-blind, parallel, randomised, controlled clinical trial to evaluate the effectiveness of a weight-loss Mediterranean dietary/lifestyle intervention on managing OSA.
This 6-month long clinical trial included 180 adult, overweight/obese moderate-to-severe OSA patients (45 patients per study group plus a 29% dropout rate). All patients were prescribed the standard of care continuous positive airway pressure (CPAP) therapy and were randomised to 3 arms: standard care; Mediterranean diet; Mediterranean lifestyle
Based on percent change in weight at 6 months, participants were categorised into a weight-stable/gain (WS/GG) group or one of 3 weight-loss groups (WLG): < 5%WLG; 5%–10%WLG; ≥ 10%WLG. Polysomnographic data and OSA symptoms were also evaluated preintervention and postintervention.
Results
Results confirm a dose-response relationship between the degree of weight loss achieved through a dietary/lifestyle intervention and improvements in OSA severity.
- Respiratory events and oximetry indices improved only in patients who lost weight. Improvements were proportional to the degree of weight loss.
- Median percent change in apnea-hypopnea index (AHI) was −11.7%, − 37.9%, and − 49.3% in the < 5%WLG, 5%–10%WLG, and ≥ 10%WLG, respectively (P < .001).
- Compared to the WS/GG, the age-, sex-, baseline-, and CPAP use–adjusted relative risk (95% confidence interval) of severe OSA (AHI ≥ 30 events/h) was 0.45 (0.23–0.87) in the 5%–10%WLG and 0.32 (0.17–0.64) in the ≥ 10%WLG; the risk was also lower in the ≥ 10%WLG vs the < 5%WLG (0.42 [0.22–0.82]).
- Insomnia and daytime sleepiness also improved more in participants exhibiting ≥ 5% weight loss.
- The dose-response relationship between weight loss and improvement in OSA severity was evident regardless of self-reported CPAP use.
Conclusions
The authors conclude that even a < 5% weight loss was sufficient for improvements in respiratory events and oximetry indices, but the prevalence of severe OSA reduced only after a ≥ 5% weight loss, and patients achieving a ≥ 10% weight loss exhibited the greatest benefits compared to weight-stable/gain patients.
Clinical practice applications:
These findings might be useful for Nutritional Therapists and Clinical Practitioners:
- Clinicians should aim for a ≥ 5% weight loss, and ideally a ≥ 10% weight loss, to achieve clinically meaningful reductions in OSA severity.
- Improvements after weight loss were significant even though a healthy body weight was not achieved.
Considerations for future research:
- The study sample consisted of predominantly male, overweight, otherwise healthy patients with moderate-to-severe OSA. Therefore, findings cannot be generalised to the whole OSA population and further research is required with broader, diverse, study samples.
- 6 months is a short duration period, therefore longer trials are required.
- Self-reported CPAP use by participants is a limitation of this study. Further robust analysis methods should be considered for future trials.
- Participants were advised to abstain from CPAP therapy for 2 days prior to the follow-up PSG but this was not evaluated or confirmed in this study and should be in future research.
Abstract
STUDY OBJECTIVES Lifestyle-induced weight loss is a complementary therapeutic approach for obstructive sleep apnea (OSA). We aimed at identifying the dose-response relationship between weight loss and OSA severity improvement. METHODS This is a secondary analysis of a 6-month clinical trial in 180 adult, overweight/obese moderate-to-severe OSA patients. Participants were randomized to a standard care, a Mediterranean diet, or a Mediterranean lifestyle arm. All patients were prescribed with continuous positive airway pressure (CPAP), while intervention arms additionally participated in a weight-loss dietary/lifestyle intervention. Based on percent change in weight at 6 months, participants were categorized into a weight-stable/gain (WS/GG) group or 3 weight-loss groups (WLG): < 5%WLG, 5%-10%WLG, and ≥ 10%WLG. Polysomnographic data and OSA symptoms were evaluated preintervention and postintervention. RESULTS Respiratory events and oximetry indices improved only in patients who lost weight and improvements were proportional to the degree of weight loss. Median percent change in apnea-hypopnea index (AHI) was -11.7%, - 37.9%, and - 49.3% in the < 5%WLG, 5%-10%WLG, and ≥ 10%WLG, respectively (P < .001). Compared to the WS/GG, the age-, sex-, baseline-, and CPAP use-adjusted relative risk (95% confidence interval) of severe OSA (AHI ≥ 30 events/h) was 0.45 (0.23-0.87) in the 5%-10%WLG and 0.32 (0.17-0.64) in the ≥ 10%WLG; the risk was also lower in the ≥ 10%WLG vs the < 5%WLG (0.42 [0.22-0.82]). Insomnia and daytime sleepiness also improved more in participants exhibiting ≥ 5% weight loss. CONCLUSIONS Even a < 5% weight loss can reduce respiratory events, but a ≥ 5% and ideally ≥ 10% weight loss is necessary for reducing the prevalence of severe OSA. CLINICAL TRIAL REGISTRATION Registry: ClinicalTrials.gov; Name: Mediterranean Diet/Lifestyle Intervention in Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT02515357; Identifier: NCT02515357. CITATION Georgoulis M, Yiannakouris N, Kechribari I, et al. Dose-response relationship between weight loss and improvements in obstructive sleep apnea severity after a diet/lifestyle intervention: secondary analyses of the "MIMOSA" randomized clinical trial. J Clin Sleep Med. 2022;18(5):1251-1261.
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The effects of the Green-Mediterranean diet on cardiometabolic health are linked to gut microbiome modifications: a randomized controlled trial.
Rinott, E, Meir, AY, Tsaban, G, Zelicha, H, Kaplan, A, Knights, D, Tuohy, K, Scholz, MU, Koren, O, Stampfer, MJ, et al
Genome medicine. 2022;14(1):29
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The Mediterranean (MED) diet, high in nuts, vegetables, and legumes and low in red meat intake, is recommended for the prevention of cardiometabolic diseases. It has been reported that adherence to MED dietary patterns is associated with a distinct gut microbiome profile. The main aim of this study was to investigate the effect of MED-based dietary interventions on the gut microbiome composition and function. This study was focused on the analysis of the DIRECT-PLUS trials’ secondary outcomes, including gut microbiome profile, lipid profile, glycaemic control, inflammatory state, and cardiometabolic risk. All eligible participants were randomised in a 1:1:1 ratio, into one of the three intervention groups: healthy dietary guidelines (HDG), MED, and Green-MED, all combined with physical activity accommodation. Results showed that: - the Green-MED diet [an improved version of the healthy MED diet, with increased consumption of plant-based foods and reduced meat intake] induced a prominent change in the gut microbiome composition, driven by the low-prevalent “non-core” fraction of the gut microbiome. - the MED and Green-MED diets improved cardiometabolic markers. These beneficial changes in levels of cardiometabolic biomarkers were associated with a concurrent shift in the gut microbiome composition. Authors conclude that the Green-MED diet has extensive effects on the composition and function of the host gut microbiome, with the latter partially mediating the beneficial effects of the diet on cardiometabolic health.
Abstract
BACKGROUND Previous studies have linked the Mediterranean diet (MED) with improved cardiometabolic health, showing preliminary evidence for a mediating role of the gut microbiome. We recently suggested the Green-Mediterranean (Green-MED) diet as an improved version of the healthy MED diet, with increased consumption of plant-based foods and reduced meat intake. Here, we investigated the effects of MED interventions on the gut microbiota and cardiometabolic markers, and the interplay between the two, during the initial weight loss phase of the DIRECT-PLUS trial. METHODS In the DIRECT-PLUS study, 294 participants with abdominal obesity/dyslipidemia were prospectively randomized to one of three intervention groups: healthy dietary guidelines (standard science-based nutritional counseling), MED, and Green-MED. Both isocaloric MED and Green-MED groups were supplemented with 28g/day walnuts. The Green-MED group was further provided with daily polyphenol-rich green tea and Mankai aquatic plant (new plant introduced to a western population). Gut microbiota was profiled by 16S rRNA for all stool samples and shotgun sequencing for a select subset of samples. RESULTS Both MED diets induced substantial changes in the community structure of the gut microbiome, with the Green-MED diet leading to more prominent compositional changes, largely driven by the low abundant, "non-core," microorganisms. The Green-MED diet was associated with specific microbial changes, including enrichments in the genus Prevotella and enzymatic functions involved in branched-chain amino acid degradation, and reductions in the genus Bifidobacterium and enzymatic functions responsible for branched-chain amino acid biosynthesis. The MED and Green-MED diets were also associated with stepwise beneficial changes in body weight and cardiometabolic biomarkers, concomitantly with the increased plant intake and reduced meat intake. Furthermore, while the level of adherence to the Green-MED diet and its specific green dietary components was associated with the magnitude of changes in microbiome composition, changes in gut microbial features appeared to mediate the association between adherence to the Green-MED and body weight and cardiometabolic risk reduction. CONCLUSIONS Our findings support a mediating role of the gut microbiome in the beneficial effects of the Green-MED diet enriched with Mankai and green tea on cardiometabolic risk factors. TRIAL REGISTRATION The study was registered on ClinicalTrial.gov ( NCT03020186 ) on January 13, 2017.
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Randomized trial of weight loss in primary breast cancer: Impact on body composition, circulating biomarkers and tumor characteristics.
Demark-Wahnefried, W, Rogers, LQ, Gibson, JT, Harada, S, Frugé, AD, Oster, RA, Grizzle, WE, Norian, LA, Yang, ES, Della Manna, D, et al
International journal of cancer. 2020;146(10):2784-2796
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Obesity directly impacts survival in individuals with breast cancer. Previous studies in animals and at the cellular level have shown that calorie restriction and increased physical activity to achieve a negative energy balance may inhibit cancer progression, however effects in patients are unknown. This randomised control trial aimed to determine the impact of a pre surgery weight loss programme in 32 women with breast cancer on tumour biology and other markers of disease. The results were mixed and showed that proteins which bind to hormones involved in breast cancer were increased, which could decrease severity of disease. However, tumour biology was negatively affected; specific genes involved in breast cancer progression were increased and those involved in tumour suppression were decreased. Although this did result in no net effect on the rate at which new tumours were formed. It was concluded that although the study showed mixed results, ultimately the rate at which new tumours were formed remained unaffected. This trial could be used by healthcare professionals to understand that the role of negative energy intake in breast cancer development is complicated and warrants further research.
Abstract
Obesity adversely impacts overall and cancer-specific survival among breast cancer patients. Preclinical studies demonstrate negative energy balance inhibits cancer progression; however, feasibility and effects in patients are unknown. A two-arm, single-blinded, randomized controlled weight-loss trial was undertaken presurgery among 32 overweight/obese, Stage 0-II breast cancer patients. The attention control arm (AC) received basic nutritional counseling and upper-body progressive resistance training whereas the weight loss intervention (WLI) arm received identical guidance, plus counseling on caloric restriction and aerobic exercise to promote 0.68-0.92 kg/week weight loss. Anthropometrics, body composition, blood and survey data were collected at baseline and presurgery ∼30 days later. Tumor markers (e.g., Ki67) and gene expression were assessed on biopsy and surgical specimens; sera were analyzed for cytokines, growth and metabolic factors. Significant WLI vs. AC differences were seen in baseline-to-follow-up changes in weight (-3.62 vs. -0.52 kg), %body fat (-1.3 vs. 0%), moderate-to-vigorous physical activity (+224 vs. +115 min/week), caloric density (-0.3 vs. 0 kcal/g), serum leptin (-12.3 vs. -4.0 ng/dl) and upregulation of tumor PI3Kinase signaling and cell cycle-apoptosis related genes (CC-ARG; all p-values <0.05). Cytolytic CD56dim NK cell expression was positively associated with weight loss; CC-ARG increased with physical activity. Increased tumor (nuclear) TNFα and IL-1β, CX3CL1 and CXCL1 gene expression was observed in the WLI. Tumor Ki67 did not differ between arms. Feasibility benchmarks included 80% accrual, 100% retention, no adverse effects and excellent adherence. Short-term weight loss interventions are feasible; however, mixed effects on tumor biology suggest unclear benefit to presurgical caloric restriction, but possible benefits of physical activity.
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Metabolic impact of weight loss induced reduction of adipose ACE-2 - Potential implication in COVID-19 infections?
Li, L, Spranger, L, Soll, D, Beer, F, Brachs, M, Spranger, J, Mai, K
Metabolism: clinical and experimental. 2020;113:154401
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Obesity is now recognised as a risk factor for increased severity of Covid-19 infections. ACE-2 is a protein that has many functions but also allows Covid-19 into cells and is particularly evident in body tissues, which store fat. It is therefore possible that Covid-19 will target fat-storing tissues in the body. This 12-month randomised control weight-loss intervention study of 143 obese individuals aimed to determine ACE-2 expression and whether it could be modified by weight loss. The results showed that ACE-2 was only present in fat storing tissue and not muscle tissue. Interestingly individuals with pre-diabetes or diabetes had the lowest levels of ACE-2. Weight loss resulted in reduced ACE-2 in fat storing tissue, which resulted in an improvement in markers for diabetes. It was concluded that reduction of ACE-2 in fat storing tissues as a result of weight loss can improve markers for diabetes and could impact the severity of Covid-19 infection. Healthcare professionals could use this study to understand how weight loss in patients with obesity could decrease their risk of severe Covid-19 infection.
Abstract
BACKGROUND & AIMS Angiotensin converting enzyme (ACE)-2 is a modulator of adipose tissue metabolism. However, human data of adipose ACE-2 is rarely available. Considering that, ACE-2 is believed to be the receptor responsible for cell entry of SARS-CoV-2, a better understanding of its regulation is desirable. We therefore characterized the modulation of subcutaneous adipose ACE-2 mRNA expression during weight loss and the impact of ACE-2 expression on weight loss induced short- and long-term improvements of glucose metabolism. METHODS 143 subjects (age > 18; BMI ≥ 27 kg/m2) were analyzed before and after a standardized 12-week dietary weight reduction program. Afterwards subjects were randomized to a 12-month lifestyle intervention or a control group (Maintain-Adults trial). Insulin sensitivity (IS) was estimated by HOMA-IR (as an estimate of liver IS) and ISIClamp (as an estimate of skeletal muscle IS). ACE-2 mRNA expression (ACE-2AT) was measured in subcutaneous adipose tissue before and after weight loss. RESULTS ACE-2AT was not affected by obesity, but was reduced in insulin resistant subjects. Weight loss resulted in a decline of ACE-2AT (29.0 (20.0-47.9) vs. 21.0 (13.0-31.0); p = 1.6 ∗ 10-7). A smaller reduction of ACE-2 AT (ΔACE-2AT) was associated with a larger improvement of ISIClamp (p = 0.013) during weight reduction over 3 months, but not with the extend of weight loss. The degree of changes in insulin resistance were preserved until month 12 and was also predicted by the weight loss induced degree of ΔACE-2AT (p = 0.011). CONCLUSIONS Our data indicate that subcutaneous adipose ACE-2 expression correlates with insulin sensitivity. Weight loss induced decline of subcutaneous adipose ACE-2 expression might affect short- and long-term improvement of myocellular insulin sensitivity, which might be also relevant in the context of ACE-2 downregulation by SARS-CoV-2. TRIAL REGISTRATION ClinicalTrials.gov number: NCT00850629, https://clinicaltrials.gov/ct2/show/NCT00850629, date of registration: February 25, 2009.
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Ketone ester supplementation blunts overreaching symptoms during endurance training overload.
Poffé, C, Ramaekers, M, Van Thienen, R, Hespel, P
The Journal of physiology. 2019;597(12):3009-3027
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Overload training is often used by endurance athletes to improve endurance performance. Overload training, however, can result in muscle protein breakdown, a catabolic state, and a decrease in muscle performance. Therefore, this randomised, double-blinded, placebo-controlled study examined the protective effects of ketone ester supplementation in reducing the detrimental effects of endurance training-induced overreaching. When compared to the control group, the subjects taking oral ketone ester supplements showed a 15% increase in sustained training load and power output and maintained energy balance. Supplementation with ketones ester inhibited the night-time increase in neurotransmitter noradrenaline and hormone adrenaline and maintained heart rate, suggesting a blunting of cardiovascular, sympathetic and hormonal symptoms caused by the endurance training overload. Growth differentiation factor 15 (GDF15) increased by training overload was negated by ketone ester intake. Further studies should be conducted to establish the long-term effects of ketone esters in training and recovery. These results can help healthcare professionals better understand how elevated blood ketones can enhance exercise performance and reduce the detrimental effects of exercise overload.
Abstract
KEY POINTS Overload training is required for sustained performance gain in athletes (functional overreaching). However, excess overload may result in a catabolic state which causes performance decrements for weeks (non-functional overreaching) up to months (overtraining). Blood ketone bodies can attenuate training- or fasting-induced catabolic events. Therefore, we investigated whether increasing blood ketone levels by oral ketone ester (KE) intake can protect against endurance training-induced overreaching. We show for the first time that KE intake following exercise markedly blunts the development of physiological symptoms indicating overreaching, and at the same time significantly enhances endurance exercise performance. We provide preliminary data to indicate that growth differentiation factor 15 (GDF15) may be a relevant hormonal marker to diagnose the development of overtraining. Collectively, our data indicate that ketone ester intake is a potent nutritional strategy to prevent the development of non-functional overreaching and to stimulate endurance exercise performance. ABSTRACT It is well known that elevated blood ketones attenuate net muscle protein breakdown, as well as negate catabolic events, during energy deficit. Therefore, we hypothesized that oral ketones can blunt endurance training-induced overreaching. Fit male subjects participated in two daily training sessions (3 weeks, 6 days/week) while receiving either a ketone ester (KE, n = 9) or a control drink (CON, n = 9) following each session. Sustainable training load in week 3 as well as power output in the final 30 min of a 2-h standardized endurance session were 15% higher in KE than in CON (both P < 0.05). KE inhibited the training-induced increase in nocturnal adrenaline (P < 0.01) and noradrenaline (P < 0.01) excretion, as well as blunted the decrease in resting (CON: -6 ± 2 bpm; KE: +2 ± 3 bpm, P < 0.05), submaximal (CON: -15 ± 3 bpm; KE: -7 ± 2 bpm, P < 0.05) and maximal (CON: -17 ± 2 bpm; KE: -10 ± 2 bpm, P < 0.01) heart rate. Energy balance during the training period spontaneously turned negative in CON (-2135 kJ/day), but not in KE (+198 kJ/day). The training consistently increased growth differentiation factor 15 (GDF15), but ∼2-fold more in CON than in KE (P < 0.05). In addition, delta GDF15 correlated with the training-induced drop in maximal heart rate (r = 0.60, P < 0.001) and decrease in osteocalcin (r = 0.61, P < 0.01). Other measurements such as blood ACTH, cortisol, IL-6, leptin, ghrelin and lymphocyte count, and muscle glycogen content did not differentiate KE from CON. In conclusion, KE during strenuous endurance training attenuates the development of overreaching. We also identify GDF15 as a possible marker of overtraining.
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Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction Support the Rate of Living and Oxidative Damage Theories of Aging.
Redman, LM, Smith, SR, Burton, JH, Martin, CK, Il'yasova, D, Ravussin, E
Cell metabolism. 2018;27(4):805-815.e4
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Following a calorie-restricted diet while maintaining adequate nutrition is known to have a beneficial effect on increasing longevity and promoting healthy ageing. Oxidative stress resulting from reactive oxygen species formation in mitochondria plays a role in accelerating ageing by damaging DNA, proteins and lipids. A calorie-restriction diet can reduce oxidative stress and cause metabolic adaptations. In this ancillary study, non-obese participants were randomly assigned to either a calorie restriction group which followed 25% calorie restriction while getting adequate nutritional support through supplementation or to a control group which included ad libitum calorie intake. After 2 years of intervention, participants in the calorie restriction group achieved 15% calorie restriction, 8.7kg weight loss and a reduction in 24-hour energy expenditure and sleep energy expenditure beyond weight loss because of metabolic adaptation. Oxidative stress and thyroid axis activity were also reduced in the calorie restriction group. Further robust studies are required to evaluate the effectiveness of calorie restriction in metabolic adaptation and oxidative stress and its effects on ageing. The results of this study can be used by healthcare professionals to understand the benefits of a nutritionally adequate calorie restriction diet on adjusting metabolic processes.
Abstract
Calorie restriction (CR) is a dietary intervention with potential benefits for healthspan improvement and lifespan extension. In 53 (34 CR and 19 control) non-obese adults, we tested the hypothesis that energy expenditure (EE) and its endocrine mediators are reduced with a CR diet over 2 years. Approximately 15% CR was achieved over 2 years, resulting in an average 8.7 kg weight loss, whereas controls gained 1.8 kg. In the CR group, EE measured over 24 hr or during sleep was approximately 80-120 kcal/day lower than expected on the basis of weight loss, indicating sustained metabolic adaptation over 2 years. This metabolic adaptation was accompanied by significantly reduced thyroid axis activity and reactive oxygen species (F2-isoprostane) production. Findings from this 2-year CR trial in healthy, non-obese humans provide new evidence of persistent metabolic slowing accompanied by reduced oxidative stress, which supports the rate of living and oxidative damage theories of mammalian aging.
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Comparison of low calorie high protein and low calorie standard protein diet on waist circumference of adults with visceral obesity and weight cycling.
Witjaksono, F, Jutamulia, J, Annisa, NG, Prasetya, SI, Nurwidya, F
BMC research notes. 2018;11(1):674
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Obesity has become one of the world’s biggest health problem. Obese individuals with a history of repeated weight loss and regain (called weight cycling) have a higher risk of developing chronic disease and increased fat mass in every cycle. The objective of the study was to evaluate the effect of a low calorie high protein diet compared to a low calorie standard protein diet on waist circumference in adults with visceral obesity. The open, randomised clinical trial recruited 61 obese subjects who are older than 20 years of age and had a history of weight cycling. Participants were randomly assigned to one of the two diet groups; high protein or standard protein. Results showed that following a low-calorie diet resulted in waist circumference reduction thus reducing visceral fat. However, protein composition in the diet plan did not affect waist circumference reduction. Authors conclude that calorie restricted diets could be suggested in the treatment of visceral obesity. Macronutrient composition can be adjusted to meet the patient’s individual needs.
Abstract
OBJECTIVES Many individuals with visceral obesity who previously had succeeded in reducing body weight regain and this loss-gain cycle repeats several times which is called as weight cycling. We aimed to evaluate the effect of a low calorie high protein diet (HP) compared to a low calorie standard protein diet (SP) on waist circumference of visceral obese adults with history of weight cycling. RESULTS In this open-randomized clinical trial, participants were asked to follow dietary plan with reduction in daily caloric intake ranging from 500 to 1000 kcal from usual daily amount with minimum daily amount of 1000 kcal for 8 weeks and were divided in two groups: HP group with protein as 22-30% total calorie intake; and SP group with protein as 12-20% total calorie intake. There was a statistically significant difference (P < 0.001) between waist circumference before and after the dietary intervention among both groups. Meanwhile, there was no statistically significant difference in the mean reduction of waist circumference between HP and SP groups (P = 0.073). Taken together, the protein proportion does not significantly affected waist circumference. Trial registration ClinicalTrials.gov NCT03374150, 11 December 2017.
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A comparative controlled trial comparing the effects of yoga and walking for overweight and obese adults.
Telles, S, Sharma, SK, Yadav, A, Singh, N, Balkrishna, A
Medical science monitor : international medical journal of experimental and clinical research. 2014;20:894-904
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Walking and yoga are types of exercise that may be useful for weight loss. The aim of this study was to compare the effects of yoga and walking on the biochemistry, body composition, balance and strength in overweight people. 68 Indian adults who were overweight or obese were allocated to either yoga or walking twice a day for 15 days. Both groups were given the same plant-based diet providing 1,650 kcal/day Both groups showed similar and significant decreases in body mass index (BMI), waist and hip circumference, lean mass, body water and total cholesterol over the 15 days. The yoga group increased serum leptin and decreased LDL cholesterol. The walking group decreased serum adiponectin and triglycerides. Since there was no control group, it was not possible to attribute the changes to the yoga or walking, rather than the diet. The authors concluded that both yoga and walking improved anthropometric variables and serum lipid profile in overweight and obese people, and that these interventions may be useful in treating obesity.
Abstract
BACKGROUND Walking and yoga have been independently evaluated for weight control; however, there are very few studies comparing the 2 with randomization. MATERIAL AND METHODS The present study compared the effects of 90 minutes/day for 15 days of supervised yoga or supervised walking on: (i) related biochemistry, (ii) anthropometric variables, (iii) body composition, (iv) postural stability, and (v) bilateral hand grip strength in overweight and obese persons. Sixty-eight participants, of whom 5 were overweight (BMI ≥25 kg/m2) and 63 were obese (BMI ≥30 kg/m2; group mean age ±S.D., 36.4±11.2 years; 35 females), were randomized as 2 groups - (i) a yoga group and (ii) a walking group - given the same diet. RESULTS All differences were pre-post changes within each group. Both groups showed a significant (p<0.05; repeated measures ANOVA, post-hoc analyses) decrease in: BMI, waist circumference, hip circumference, lean mass, body water, and total cholesterol. The yoga group increased serum leptin (p<0.01) and decreased LDL cholesterol (p<0.05). The walking group decreased serum adiponectin (p<0.05) and triglycerides (p<0.05). CONCLUSIONS Both yoga and walking improved anthropometric variables and serum lipid profile in overweight and obese persons. The possible implications are discussed.