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An Energy-Reduced Mediterranean Diet, Physical Activity, and Body Composition: An Interim Subgroup Analysis of the PREDIMED-Plus Randomized Clinical Trial.
Konieczna, J, Ruiz-Canela, M, Galmes-Panades, AM, Abete, I, Babio, N, Fiol, M, Martín-Sánchez, V, Estruch, R, Vidal, J, Buil-Cosiales, P, et al
JAMA network open. 2023;6(10):e2337994
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The Mediterranean diet (MedDiet), which focuses on whole grains, lean meat, fruits, vegetables, and low amounts of minimally processed foods has been shown in previous research to improve body composition and decrease fat storage around the middle. This randomised control trial of 1556 older adults aimed to determine the effects of combining a 30% lower energy version of the MedDiet in combination with physical exercise on body composition. After 3 years, the results showed that compared to a normal MedDiet without exercise, the lower energy version in combination with exercise improved body composition by decreasing total fat, and the fat stored around the organs and increasing muscle mass. However, benefits were more pronounced after 1 year and decreased slightly at 3 years. It was concluded that a low energy MedDiet in combination with physical activity may be able to improve the body composition of overweight and older adults with obesity. This study could be used by healthcare professionals to recommend a low energy MedDiet to older adults to promote weight loss, whilst attenuating muscle loss associated with ageing.
Abstract
IMPORTANCE Strategies targeting body composition may help prevent chronic diseases in persons with excess weight, but randomized clinical trials evaluating lifestyle interventions have rarely reported effects on directly quantified body composition. OBJECTIVE To evaluate the effects of a lifestyle weight-loss intervention on changes in overall and regional body composition. DESIGN, SETTING, AND PARTICIPANTS The ongoing Prevención con Dieta Mediterránea-Plus (PREDIMED-Plus) randomized clinical trial is designed to test the effect of the intervention on cardiovascular disease prevention after 8 years of follow-up. The trial is being conducted in 23 Spanish research centers and includes men and women (age 55-75 years) with body mass index between 27 and 40 and metabolic syndrome. The trial reported herein is an interim subgroup analysis of the intermediate outcome body composition after 3-year follow-up, and data analysis was conducted from February 1 to November 30, 2022. Of 6874 total PREDIMED-Plus participants, a subsample of 1521 individuals, coming from centers with access to a dual energy x-ray absorptiometry device, underwent body composition measurements at 3 time points. INTERVENTION Participants were randomly allocated to a multifactorial intervention based on an energy-reduced Mediterranean diet (MedDiet) and increased physical activity (PA) or to a control group based on usual care, with advice to follow an ad libitum MedDiet, but no physical activity promotion. MAIN OUTCOMES AND MEASURES The outcomes (continuous) were 3-year changes in total fat and lean mass (expressed as percentages of body mass) and visceral fat (in grams), tested using multivariable linear mixed-effects models. Clinical relevance of changes in body components (dichotomous) was assessed based on 5% or more improvements in baseline values, using logistic regression. Main analyses were performed in the evaluable population (completers only) and in sensitivity analyses, multiple imputation was performed to include data of participants lost to follow-up (intention-to-treat analyses). RESULTS A total of 1521 individuals were included (mean [SD] age, 65.3 [5.0] years; 52.1% men). In comparison with the control group (n=761), participants in the intervention arm (n=760) showed greater reductions in the percentage of total fat (between group differences after 1-year, -0.94% [95% CI, -1.19 to -0.69]; 3 years, -0.38% [95% CI, -0.64 to -0.12] and visceral fat storage after 1 year, -126 g [95% CI, -179 to -73.3 g]; 3 years, -70.4 g [95% CI, -126 to -15.2 g] and greater increases in the percentage of total lean mass at 1 year, 0.88% [95% CI, 0.63%-1.12%]; 3-years 0.34% [95% CI, 0.09%-0.60%]). The intervention group was more likely to show improvements of 5% or more in baseline body components (absolute risk reduction after 1 year, 13% for total fat mass, 11% for total lean mass, and 14% for visceral fat mass; after 3-years: 6% for total fat mass, 6% for total lean mass, and 8% for visceral fat mass). The number of participants needed to treat was between 12 and 17 to attain at least 1 individual with possibly clinically meaningful improvements in body composition. CONCLUSIONS AND RELEVANCE The findings of this trial suggest a weight-loss lifestyle intervention based on an energy-reduced MedDiet and physical activity significantly reduced total and visceral fat and attenuated age-related losses of lean mass in older adults with overweight or obesity and metabolic syndrome. Continued follow-up is warranted to confirm the long-term consequences of these changes on cardiovascular clinical end points. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN89898870.
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Nicotinamide Riboside Enhances In Vitro Beta-adrenergic Brown Adipose Tissue Activity in Humans.
Nascimento, EBM, Moonen, MPB, Remie, CME, Gariani, K, Jörgensen, JA, Schaart, G, Hoeks, J, Auwerx, J, van Marken Lichtenbelt, WD, Schrauwen, P
The Journal of clinical endocrinology and metabolism. 2021;106(5):1437-1447
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Brown fat is a type of fat that burns energy to regulate the body’s temperature in cold conditions. A high level of activity in the brown fat has been associated with healthy whole-body metabolism. Several supplements have been investigated for their potential to activate brown fat, however many of these have limiting side effects. Nicotinamide riboside (NR), also known as vitamin B3, is a supplement which can boost energy burning pathways within the body. This randomised control trial was part of a larger trial including a study on human brown fat cells and aimed to determine whether NR supplementation in overweight and obese individuals may act on the activity of brown tissue. The results showed that 6 weeks of NR supplementation had no effect on brown tissue activity or energy expenditure. It was concluded that NR supplementation for 6 weeks in individuals with obesity had no effect on brown fat tissue for reasons unknown, as the cellular study showed an increase in activity. This study could be used by healthcare professionals to better understand the role of brown fat in metabolism.
Abstract
CONTEXT Elevating nicotinamide adenine dinucleotide (NAD+) levels systemically improves metabolic health, which can be accomplished via nicotinamide riboside (NR). Previously, it was demonstrated that NR supplementation in high-fat-diet (HFD)-fed mice decreased weight gain, normalized glucose metabolism, and enhanced cold tolerance. OBJECTIVE Because brown adipose tissue (BAT) is a major source of thermogenesis, we hypothesize that NR stimulates BAT in mice and humans. DESIGN AND INTERVENTION HFD-fed C56BL/6J mice were supplemented with 400 mg/kg/day NR for 4 weeks and subsequently exposed to cold. In vitro primary adipocytes derived from human BAT biopsies were pretreated with 50 µM or 500 µM NR before measuring mitochondrial uncoupling. Human volunteers (45-65 years; body mass index, 27-35 kg/m2) were supplemented with 1000 mg/day NR for 6 weeks to determine whether BAT activity increased, as measured by [18F]FDG uptake via positron emission tomography-computed tomography (randomized, double blinded, placebo-controlled, crossover study with NR supplementation). RESULTS NR supplementation in HFD-fed mice decreased adipocyte cell size in BAT. Cold exposure further decreased adipocyte cell size on top of that achieved by NR alone independent of ex vivo lipolysis. In adipocytes derived from human BAT, NR enhanced in vitro norepinephrine-stimulated mitochondrial uncoupling. However, NR supplementation in human volunteers did not alter BAT activity or cold-induced thermogenesis. CONCLUSIONS NR stimulates in vitro human BAT but not in vivo BAT in humans. Our research demonstrates the need for further translational research to better understand the differences in NAD+ metabolism in mouse and human.
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Brown Adipose Crosstalk in Tissue Plasticity and Human Metabolism.
Scheele, C, Wolfrum, C
Endocrine reviews. 2020;41(1)
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Brown adipose tissue (BAT) is an important contributor to the regulation of metabolism via cellular communication with organs such as liver, muscle, gut and central nervous system. BAT is important for heat generation and is at high levels in human infants. Levels of activation of BAT decline as we age and it has been shown that the amount of BAT is smaller and its activity reduced in those with obesity and type 2 diabetes. To date, there is no answer to efficiently restore functional BAT in aging and obese subjects. This review looks at experiments done on the factors secreted from active BAT (batokines). The review aims to provide a structure for the processes and cell types involved in BAT and the recent findings of BAT whole-body communication are discussed. Altogether, these findings demonstrate that BAT has an adaptive capacity. Studying batokines, offers an alternative approach to identify novel drug targets for metabolic regulation.
Abstract
Infants rely on brown adipose tissue (BAT) as a primary source of thermogenesis. In some adult humans, residuals of brown adipose tissue are adjacent to the central nervous system and acute activation increases metabolic rate. Brown adipose tissue (BAT) recruitment occurs during cold acclimation and includes secretion of factors, known as batokines, which target several different cell types within BAT, and promote adipogenesis, angiogenesis, immune cell interactions, and neurite outgrowth. All these processes seem to act in concert to promote an adapted BAT. Recent studies have also provided exciting data on whole body metabolic regulation with a broad spectrum of mechanisms involving BAT crosstalk with liver, skeletal muscle, and gut as well as the central nervous system. These widespread interactions might reflect the property of BAT of switching between an active thermogenic state where energy is highly consumed and drained from the circulation, and the passive thermoneutral state, where energy consumption is turned off. (Endocrine Reviews 41: XXX - XXX, 2020).
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Effect of A Very Low-Calorie Ketogenic Diet on Food and Alcohol Cravings, Physical and Sexual Activity, Sleep Disturbances, and Quality of Life in Obese Patients.
Castro, AI, Gomez-Arbelaez, D, Crujeiras, AB, Granero, R, Aguera, Z, Jimenez-Murcia, S, Sajoux, I, Lopez-Jaramillo, P, Fernandez-Aranda, F, Casanueva, FF
Nutrients. 2018;10(10)
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Obesity is a multi-factorial disorder involving genetic, environmental, metabolic and behavioural factors. Few studies have examined the effect of weight-loss therapy on various psychobiological parameters associated with obesity. Therefore the aim of this 4-month nutritional intervention was to evaluate food and alcohol cravings, physical activity levels, sleep quality, sexual function and quality of life in patients with obesity after following a very low-calorie ketogenic (VLCK) diet. Twenty obese patients were enrolled and participated in psychological questionnaires and anthropometric measurements at four points throughout the intervention: at baseline, maximum ketosis, reduced ketosis and endpoint. A specialist physician and expert dietician closely monitored participants to ensure safety and duration of the ketosis state. This study found that rapid and sustained weight loss induced by a VLCK-diet is associated with better food control and improvements in quality of life in obese subjects. Based on these results, the authors conclude a VLCK-diet is a suitable and valuable treatment option for obese patients.
Abstract
Psychological well-being and hunger and food control are two relevant factors involved in the success of weight-loss therapy in treating obesity. Thus, this study aims to evaluate food and alcohol cravings, physical and sexual activity, sleep, and life quality (QoL) in obese patients following a very low-calorie ketogenic (VLCK) diet, as well as the role of weight lost and ketosis on these parameters. A battery of psychological test was performed in twenty obese patients (12 females, 47.2 ± 10.2 year and BMI of 35.5 ± 4.4) through the course of a 4-month VLCK diet on four subsequent visits: baseline, maximum ketosis, reduced ketosis, and endpoint. Each subject acted as their own control. Relevantly, the dietary-induced changes in body composition (7.7 units of BMI lost, 18 kg of fat mass (1.2 kg of visceral fat mass)) were associated with a statistically significant improvement in food craving scores, physical activity, sleepiness, and female sexual function. Overall, these results also translated in a notable enhancement in QoL of the treated obese patients. Therefore, the rapid and sustained weight and fat mass (FM) loss induced by the VLCK diet is associated with good food control and improvements in the psychological well-being parameters in obese subjects, which could contribute to the long-term success of this therapy.
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Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial.
Trepanowski, JF, Kroeger, CM, Barnosky, A, Klempel, MC, Bhutani, S, Hoddy, KK, Gabel, K, Freels, S, Rigdon, J, Rood, J, et al
JAMA internal medicine. 2017;177(7):930-938
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Restricting calories every second day to as low as 500 calories (alternate day fasting) has become popular in recent years as a weight loss strategy. This randomised clinical trial of 69 obese, but otherwise healthy, individuals aimed to assess the impact of alternate day fasting for 6 months on weight loss and risk factors for heart disease, in comparison to more traditional daily calorie restriction. The study results showed that average weight loss was similar for the alternate day fasting group and daily calorie restriction group, compared to control. Average HDL cholesterol levels were higher at month 6 and average LDL cholesterol levels were higher at month 12 in the alternate day fasting group, compared to the daily calorie restriction group. There were no other statistically significant differences between the 2 groups for other markers of heart disease. Drop out rates were highest in the alternate day fasting group, suggesting that it is a harder diet to stick to in the longer term. Nutrition practitioners practising individualised nutrition can use the results of this trial to work with overweight clients in choosing the best dietary strategy for weight loss in relation to their clients’ goals and lifestyle.
Abstract
Importance: Alternate-day fasting has become increasingly popular, yet, to date, no long-term randomized clinical trials have evaluated its efficacy. Objective: To compare the effects of alternate-day fasting vs daily calorie restriction on weight loss, weight maintenance, and risk indicators for cardiovascular disease. Design, Setting, and Participants: A single-center randomized clinical trial of obese adults (18 to 64 years of age; mean body mass index, 34) was conducted between October 1, 2011, and January 15, 2015, at an academic institution in Chicago, Illinois. Interventions: Participants were randomized to 1 of 3 groups for 1 year: alternate-day fasting (25% of energy needs on fast days; 125% of energy needs on alternating "feast days"), calorie restriction (75% of energy needs every day), or a no-intervention control. The trial involved a 6-month weight-loss phase followed by a 6-month weight-maintenance phase. Main Outcomes and Measures: The primary outcome was change in body weight. Secondary outcomes were adherence to the dietary intervention and risk indicators for cardiovascular disease. Results: Among the 100 participants (86 women and 14 men; mean [SD] age, 44 [11] years), the dropout rate was highest in the alternate-day fasting group (13 of 34 [38%]), vs the daily calorie restriction group (10 of 35 [29%]) and control group (8 of 31 [26%]). Mean weight loss was similar for participants in the alternate-day fasting group and those in the daily calorie restriction group at month 6 (-6.8% [95% CI, -9.1% to -4.5%] vs -6.8% [95% CI, -9.1% to -4.6%]) and month 12 (-6.0% [95% CI, -8.5% to -3.6%] vs -5.3% [95% CI, -7.6% to -3.0%]) relative to those in the control group. Participants in the alternate-day fasting group ate more than prescribed on fast days, and less than prescribed on feast days, while those in the daily calorie restriction group generally met their prescribed energy goals. There were no significant differences between the intervention groups in blood pressure, heart rate, triglycerides, fasting glucose, fasting insulin, insulin resistance, C-reactive protein, or homocysteine concentrations at month 6 or 12. Mean high-density lipoprotein cholesterol levels at month 6 significantly increased among the participants in the alternate-day fasting group (6.2 mg/dL [95% CI, 0.1-12.4 mg/dL]), but not at month 12 (1.0 mg/dL [95% CI, -5.9 to 7.8 mg/dL]), relative to those in the daily calorie restriction group. Mean low-density lipoprotein cholesterol levels were significantly elevated by month 12 among the participants in the alternate-day fasting group (11.5 mg/dL [95% CI, 1.9-21.1 mg/dL]) compared with those in the daily calorie restriction group. Conclusions and Relevance: Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or cardioprotection vs daily calorie restriction. Trial Registration: clinicaltrials.gov Identifier: NCT00960505.
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Consuming High-Protein Soy Snacks Affects Appetite Control, Satiety, and Diet Quality in Young People and Influences Select Aspects of Mood and Cognition.
Leidy, HJ, Todd, CB, Zino, AZ, Immel, JE, Mukherjea, R, Shafer, RS, Ortinau, LC, Braun, M
The Journal of nutrition. 2015;145(7):1614-22
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Snacking is contributing to the obesity crisis, with obese individuals tending to favour high fat (HF) and/or high sugar snacks. It is unclear whether replacing the HF and/or high sugar snacks with a healthier alternative could improve obesity overcomes in young people. The aim of this small randomised, cross-over designed trial was to compare the effects high-protein (HP), HF afternoon snacks and no snacks (NoS) on measures including appetite, satiety and cognition. Thirty one healthy adolescents consumed HP, HF afternoon snacks or NoS in a random order over a three day period. Participants were observed in laboratory conditions for an eight hour period for each of the three day plus the fourth. Laboratory tests included functional magnetic renascence imaging (fMRI), food and mood questionnaires and cognitive tests. It was found that a HP snack improved appetite control and satiety compared to a HF snack or NoS. Additional a HP snack led to a reduction in the consumption of HF/high-sugar snacks later in the evening. No difference in cognition was detected between any of the groups.
Abstract
BACKGROUND Data concerning the effects of afternoon snacking on ingestive behavior, mood, and cognition are limited. OBJECTIVE The purpose of this study was to compare 1088 kJ of high-protein (HP) or high-fat (HF) afternoon snacks vs. no snacking on appetite, food intake, mood, and cognition in adolescents. METHODS Thirty-one healthy adolescents (age: 17 ± 1 y) consumed the following afternoon snacks (in randomized order) for 3 d: HP snack (26 g of protein/6 g of fat per 27 g of carbohydrates), HF snack (4 g of protein/12 g of fat per 32 g of carbohydrates), and no snack (NoS). On day 4 of each treatment, the participants completed an 8-h testing day containing pre- and postsnack appetite questionnaires, food cue-stimulated functional MRI brain scans, mood, cognitive function, and eating initiation. Ad libitum dinner and evening snacks were provided and assessed. RESULTS HP, but not HF, delayed eating initiation vs. NoS (P < 0.05). Both snacks reduced appetite vs. NoS (P < 0.001) with HP eliciting greater reductions than HF (P < 0.05). Only HF led to reductions in corticolimbic activation in brain regions controlling food motivation/reward vs. NoS (P < 0.01). Although no treatment differences in daily energy intake were detected, HP led to greater protein consumption than NoS (P < 0.05) and greater protein and lower fat consumption than HF (both, P < 0.05). HP led to fewer HF/high-sugar evening snacks than NoS (P < 0.01) and HF (P = 0.09). Although no treatment effects were detected for mood and cognition, HP tended to reduce confusion-bewilderment (P = 0.07) and increase cognitive flexibility (P = 0.09), whereas NoS reduced tension-anxiety (P < 0.05) and vigor-activity (P < 0.05). CONCLUSION Afternoon snacking, particularly on HP soy foods, improves appetite, satiety, and diet quality in adolescents, while beneficially influencing aspects of mood and cognition. This trial was registered at clinicaltrials.gov as NCT01781286.