The multidirectional assessment of moderate caloric restriction and metformin treatment in obese patients.

Obesity treatment is often burdensome for patients. We used the combination of moderate caloric restriction (CR) with hypoglycemic metformin to assess their multidirectional effect in obese patients. One group was treated only with moderate CR (n=21) the second was treated with moderate CR and 800 mg metformin twice daily (n=23). Serum was drawn before and after treatment. The following parameters were monitored: anthropometric, cardiovascular, inflammatory, metabolic, and markers characteristic for thyroid, liver, pancreas, and kidney functions. Both tested groups did not significantly differ in most tested parameters after the treatment. Two groups reduced anthropometric parameters (body mass, body mass index (BMI), waist circumference) and fat mass but also muscle and fat-free mass, improving systolic blood pressure, insulin and leptin concentration, insulin sensitivity, leptin to adiponectin ratio, and inflammatory markers. Unfortunately, there was little impact on improving dyslipidemia and the thyroid and liver parameters. Free triiodothyronine (fT3) and gamma glutamyl transferase (GGT) activity were decreased in both groups, but triglycerides were reduced only in patients treated with moderate CR. Metformin with CR treatment decreases uric acid and aspartate aminotransferase (AspAT) activity. Metformin treatment with moderate CR in obese patients mainly improved insulin sensitivity, resulting in a reduction of patients with glucose intolerance, improved anthropometric, cardiovascular, and inflammatory mediators, and only slightly enhanced liver and thyroid function. No changes in kidney and pancreas function were observed during the treatment. In conclusion, eight weeks of CR alone and CR with metformin in obese adults improved anthropometric and metabolic markers, reduced muscle mass, fT3, GGT, proinflammatory, and CV parameters, and displayed no changes in kidney and pancreas function. The group treated with metformin after the treatment was still more obese and had higher C-reactive protein (CRP) and homeostasis model assessment-an index of insulin resistance (HOMA-IR), but despite this, considerably reduced the number of patients with glucose intolerance.

Adaptive thermogenesis, at the level of resting energy expenditure, after diet alone or diet plus bariatric surgery.

OBJECTIVE: The objective of this study was to compare the magnitude of adaptive thermogenesis (AT), at the level of resting energy expenditure (REE), after a very low-energy diet alone or combined with Roux-en-Y gastric bypass or sleeve gastrectomy, as well as to investigate the association between AT and changes in appetite. METHODS: A total of 44 participants with severe obesity underwent 10 weeks of a very low-energy diet alone or combined with Roux-en-Y gastric bypass or sleeve gastrectomy. Body weight and composition, REE, subjective appetite feelings, and plasma concentrations of gastrointestinal hormones were measured at baseline and week 11. AT, at the level of REE, was defined as a significantly lower measured versus predicted (using a regression model with baseline data) REE. RESULTS: Participants lost 18.4 ± 3.9 kg of body weight and experienced AT, at the level of REE (-121 ± 188 kcal/day; p < 0.001), with no differences among groups. The larger the AT, at the level of REE, the greater the reduction in fasting ghrelin concentrations and the smaller the reduction in feelings of hunger and desire to eat in the postprandial state. CONCLUSIONS: Weight-loss modality does not seem to modulate the magnitude of AT, at the level of REE. The greater the AT, at the level of REE, the greater the drive to eat following weight loss.

Normalisation and equity of referral to the NHS Low Calorie Diet programme pilot; a qualitative evaluation of the experiences of health care staff.

BACKGROUND: Health and wellbeing can be profoundly impacted by both obesity and type 2 diabetes, while the normalisation and equity of care for people living with these non-communicable diseases remain as challenges for local health systems. The National Health Service Low Calorie Diet programme in England, aims to support people to achieve type 2 diabetes remission, while also reducing health inequalities. We have explored the experiences of health care staff who have made a referral to the LCD programme, while identifying effective and equitable delivery of programme referrals, and their normalisation into routine care. METHODS: Nineteen individual semi-structured interviews were completed health care staff in the first year of the Low Calorie Diet programme. Interviewees were purposively sampled from the ten localities who undertook the Low Calorie Diet programme pilot. Each interview explored a number of topics of interest including communication and training, referrals, equity, and demands on primary care, before being subjected to a thematic analysis. RESULTS: From the data, five core themes were identified: Covid-19 and the demands on primary care, the expertise and knowledge of referrers, patient identification and the referral process, barriers to referrals and who gets referred to the NHS LCD programme. Our findings demonstrate the variation in the real world settings of a national diabetes programme. It highlights the challenge of COVID-19 for health care staff, whereby the increased workload of referrals occurred at a time when capacity was curtailed. We have also identified several barriers to referral and have shown that referrals had not yet been normalised into routine care at the point of data collection. We also raise issues of equity in the referral process, as not all eligible people are informed about the programme. CONCLUSIONS: Referral generation had not yet been consistently normalised into routine care, yet our findings suggest that the LCD programme runs the risk of normalising an inequitable referral process. Inequalities remain a significant challenge, and the adoption of an equitable referral process, normalised at a service delivery level, has the capacity to contribute to the improvement of health inequalities.

Vascular Aging: Assessment and Intervention.

Vascular aging represents a collection of structural and functional changes in a blood vessel with advancing age, including increased stiffness, vascular wall remodeling, loss of angiogenic ability, and endothelium-dependent vasodilation dysfunction. These age-related alterations may occur earlier in those who are at risk for or have cardiovascular diseases, therefore, are defined as early or premature vascular aging. Vascular aging contributes independently to cardio-cerebral vascular diseases (CCVDs). Thus, early diagnosis and interventions targeting vascular aging are of paramount importance in the delay or prevention of CCVDs. Here, we review the direct assessment of vascular aging by examining parameters that reflect changes in structure, function, or their compliance with age including arterial wall thickness and lumen diameter, endothelium-dependent vasodilation, arterial stiffness as well as indirect assessment through pathological studies of biomarkers including endothelial progenitor cell, lymphocytic telomeres, advanced glycation end-products, and C-reactive protein. Further, we evaluate how different types of interventions including lifestyle mediation, such as caloric restriction and salt intake, and treatments for hypertension, diabetes, and hyperlipidemia affect age-related vascular changes. As a single parameter or intervention targets only a certain vascular physiological change, it is recommended to use multiple parameters to evaluate and design intervention approaches accordingly to prevent systemic vascular aging in clinical practices or population-based studies.

GDF15 promotes weight loss by enhancing energy expenditure in muscle.

Caloric restriction that promotes weight loss is an effective strategy for treating non-alcoholic fatty liver disease and improving insulin sensitivity in people with type 2 diabetes1. Despite its effectiveness, in most individuals, weight loss is usually not maintained partly due to physiological adaptations that suppress energy expenditure, a process known as adaptive thermogenesis, the mechanistic underpinnings of which are unclear2,3. Treatment of rodents fed a high-fat diet with recombinant growth differentiating factor 15 (GDF15) reduces obesity and improves glycaemic control through glial-cell-derived neurotrophic factor family receptor α-like (GFRAL)-dependent suppression of food intake4-7. Here we find that, in addition to suppressing appetite, GDF15 counteracts compensatory reductions in energy expenditure, eliciting greater weight loss and reductions in non-alcoholic fatty liver disease (NAFLD) compared to caloric restriction alone. This effect of GDF15 to maintain energy expenditure during calorie restriction requires a GFRAL-ß-adrenergic-dependent signalling axis that increases fatty acid oxidation and calcium futile cycling in the skeletal muscle of mice. These data indicate that therapeutic targeting of the GDF15-GFRAL pathway may be useful for maintaining energy expenditure in skeletal muscle during caloric restriction.

Evolution Under Dietary Restriction Increases Reproduction at the Cost of Decreased Somatic Growth.

Dietary restriction (DR) is cited as the most reliable means of extending life span in a wide range of taxa, yet the evolutionary basis of the DR effect on life span remains unclear. The resource reallocation hypothesis proposes that the longevity-extending response of DR is adaptive and stems from the reallocation of resources from reproduction to somatic maintenance under food-limited conditions. However, if DR continues for multiple generations, such a response becomes maladaptive, and genotypes with higher fecundity should be selectively favored over genotypes with longer longevity. To test this prediction, we exposed replicate populations of the rotifer Brachionus dorcas, a model organism for aging and experimental evolution studies, to DR and ad-libitum (AL) diets for 100 days. During the selection experiment, AL-selected populations showed higher growth rates and mictic ratios than DR-selected populations. After approximately 27 asexual generations of selection, populations with a DR selection history had a higher net reproductive rate but lower body volume and ingestion rate in the absence of survival costs than populations with an AL selection history when they were assayed on an AL diet. Our results are inconsistent with the prediction that evolution on sustained DR increases reproduction and reduces life span, and show for the first time that sustained DR selects for clones with higher energy investment in reproduction but lower investment in somatic growth.

A Mesocosm Experiment in Ecological Physiology: The Modulation of Energy Budget in a Hibernating Marsupial under Chronic Caloric Restriction.

AbstractDuring the past 60 years, mammalian hibernation (i.e., seasonal torpor) has been interpreted as a physiological adaptation for energy economy. However, direct field comparisons of energy expenditure and torpor use in hibernating and active free-ranging animals are scarce. Here, we followed the complete hibernation cycle of a fat-storing hibernator, the marsupial Dromiciops gliroides, in its natural habitat. Using replicated mesocosms, we experimentally manipulated energy availability and measured torpor use, hibernacula use, and social clustering throughout the entire hibernation season. Also, we measured energy flow using daily food intake, daily energy expenditure (DEE), and basal metabolic rate (BMR) in winter. We hypothesized that when facing chronic caloric restriction (CCR), a hibernator should maximize torpor frequency to compensate for the energetic deficit, compared with individuals fed ad lib. (controls). However, being torpid at low temperatures could increase other burdens (e.g., cost of rewarming, freezing risks). Our results revealed that CCR animals, compared with control animals, did not promote heat conservation strategies (i.e., clustering and hibernacula use). Instead, they gradually increased torpor frequency and reduced DEE and, as a consequence, recovered weight at the end of the season. Also, CCR animals consumed food at a rate of 50.8 kJ d-1, whereas control animals consumed food at a rate of 98.4 kJ d-1. Similarly, the DEE of CCR animals in winter was 47.3±5.64 kJ d-1, which was significantly lower than control animals (DEE=88.0±5.84 kJ d-1). However, BMR and lean mass of CCR and control animals did not vary significantly, suggesting that animals maintained full metabolic capacities. This study shows that the use of torpor can be modulated depending on energy supply, thus optimizing energy budgeting. This plasticity in the use of heterothermy as an energy-saving strategy would explain the occurrence of this marsupial in a broad latitudinal and altitudinal range. Overall, this study suggests that hibernation is a powerful strategy to modulate energy expenditure in mammals from temperate regions.

Reply to Landry et al. Findings from Diet Comparison Difficult to Interpret in the Absence of Adherence Assessment. Comment on "Tricò et al. Effects of Low-Carbohydrate versus Mediterranean Diets on Weight Loss, Glucose Metabolism, Insulin Kinetics and ß-Cell Function in Morbidly Obese Individuals. Nutrients 2021, 13, 1345".

We thank Dr. Landry and colleagues [...].

The iMPROVE Study; Design, Dietary Patterns, and Development of a Lifestyle Index in Overweight and Obese Greek Adults.

BACKGROUND: Dietary and lifestyle habits constitute a significant contributing factor in the formation of anthropometric and biochemical characteristics of overweight and obese populations. The iMPROVE study recruited overweight and obese Greek adults and investigated the effect of gene-diet interactions on weight management when adhering to a six-month, randomized nutritional trial including two hypocaloric diets of different macronutrient content. The present paper displays the design of the intervention and the baseline findings of the participants' dietary habits and their baseline anthropometric and biochemical characteristics. METHODS: Baseline available data for 202 participants were analyzed and patterns were extracted via principal component analysis (PCA) on 69-item Food-Frequency Questionnaires (FFQ). Relationships with indices at baseline were investigated by multivariate linear regressions. A Lifestyle Index of five variables was further constructed. RESULTS: PCA provided 5 dietary patterns. The "Mixed" pattern displayed positive associations with logBMI and logVisceral fat, whereas the "Traditional, vegetarian-alike" pattern was nominally, negatively associated with body and visceral fat, but positively associated with HDL levels. The Lifestyle Index displayed protective effects in the formation of logBMI and logGlucose levels. CONCLUSIONS: Dietary patterns and a Lifestyle Index in overweight and obese, Greek adults highlighted associations between diet, lifestyle, and anthropometric and biochemical indices.

[Assessment of the professional community awareness about innovative diets prescribed for hypertension].

Due to the fact of constantly increasing incidence of arterial hypertension and the large role of nutrition in the treatment and prevention of this disease, the assessment of the awareness of the medical community and patients about the trends in the development of therapeutic and prophylactic diets is relevant. The aim of the research was to assess the physician and patient awareness on the trends in the development of therapeutic and prophylactic diets and different rations prescribed for hypertension prevention. Material and methods. On the SurveyMonkey platform, questionnaires were created for different medical specialties and patient of various departments. Access to the survey was free, the mailing list was carried out through the professional communities of physicians on the Internet. In turn, the doctors-respondents were asked to distribute the link for patients among those who were undergoing treatment or were on dispensary observation for the pathology of the cardiovascular system. Respondents were asked about their attitudes, knowledge, and compliance with existing dietary guidelines. The number of respondents was 300 doctors of various specialties and 300 patients. Results. The most recognizable dietary recommendations among patients were: low-calorie (41.1%), low-carbohydrate (39.4%), vegetarian (39.0%). However, the most popular (the commitment to them was the greatest) were: low in calories (27.6%), low in carbohydrates (25.6%), low in fat (24.4%). Among the doctors, the distribution was as follows - in addition to the classic therapeutic and prophylactic diets prescribed for certain diseases, the most recognizable diets were: Mediterranean (59.8%), low-calorie (59.0%), low-fat (57.3%); and the most commonly prescribed: Mediterranean (47.0%), low-carb (44.4%), low-fat (40.2%). The most recognizable dietary pattern among patients was the low-calorie diet (adherence to it was also maximum). As for physicians, the most recognized and most recommended preventively was the Mediterranean eating pattern. At the same time, the prevalence and recognition of the DASH diet, which, according to the opinion of the world community, has the most pronounced preventive and therapeutic properties, according to the survey, was low (7.3% of the respondents were aware of this diet). Conclusions. According to the results of this work, it is necessary to consider the possibility of combining three diets (low-calorie, Mediterranean and DASH diets) to achieve the maximum therapeutic and preventive effect while maintaining popularity among patients.

Short-term protein restriction at advanced age stimulates FGF21 signalling, energy expenditure and browning of white adipose tissue.

Dietary protein restriction has been demonstrated to improve metabolic health under various conditions. However, the relevance of ageing and age-related decline in metabolic flexibility on the effects of dietary protein restriction has not been addressed. Therefore, we investigated the effect of short-term dietary protein restriction on metabolic health in young and aged mice. Young adult (3 months old) and aged (18 months old) C57Bl/6J mice were subjected to a 3-month dietary protein restriction. Outcome parameters included fibroblast growth factor 21 (FGF21) levels, muscle strength, glucose tolerance, energy expenditure (EE) and transcriptomics of brown and white adipose tissue (WAT). Here, we report that a low-protein diet had beneficial effects in aged mice by reducing some aspects of age-related metabolic decline. These effects were characterized by increased plasma levels of FGF21, browning of subcutaneous WAT, increased body temperature and EE, while no changes were observed in glucose homeostasis and insulin sensitivity. Moreover, the low-protein diet used in this study was well-tolerated in aged mice indicated by the absence of adverse effects on body weight, locomotor activity and muscle performance. In conclusion, our study demonstrates that a short-term reduction in dietary protein intake can impact age-related metabolic health alongside increased FGF21 signalling, without negatively affecting muscle function. These findings highlight the potential of protein restriction as a strategy to induce EE and browning of WAT in aged individuals.

Impact of an 8-Year Intensive Lifestyle Intervention on an Index of Multimorbidity.

BACKGROUND/OBJECTIVES: Type 2 diabetes mellitus and obesity are sometimes described as conditions that accelerate aging. Multidomain lifestyle interventions have shown promise to slow the accumulation of age-related diseases, a hallmark of aging. However, they have not been assessed among at-risk individuals with these two conditions. We examined the relative impact of 8 years of a multidomain lifestyle intervention on an index of multimorbidity. DESIGN: Randomized controlled clinical trial comparing an intensive lifestyle intervention (ILI) that targeted weight loss through caloric restriction and increased physical activity with a control condition of diabetes support and education (DSE). SETTING: Sixteen U.S. academic centers. PARTICIPANTS: A total of 5,145 volunteers, aged 45 to 76, with established type 2 diabetes mellitus and overweight or obesity who met eligibility criteria for a randomized controlled clinical trial. MEASUREMENTS: A multimorbidity index that included nine age-related chronic diseases and death was tracked over 8 years of intervention delivery. RESULTS: Among individuals assigned to DSE, the multimorbidity index scores increased by an average of .98 (95% confidence interval [CI] = .94-1.02) over 8 years, compared with .89 (95% CI = .85-.93) among those in the multidomain ILI, which was a 9% difference (P = .003). Relative intervention effects were similar among individuals grouped by baseline body mass index, age, and sex, and they were greater for those with lower levels of multimorbidity index scores at baseline. CONCLUSIONS: Increases in multimorbidity over time among adults with overweight or obesity and type 2 diabetes mellitus may be slowed by multidomain ILI. J Am Geriatr Soc 68:2249-2256, 2020.

[Assessment of nutritional-dietary status, body composition, eating behavior, and perceived image in rhythmic gymnastics athletes]. / Valoración del estado dietético-nutricional, la composición corporal, el comportamiento alimentario y la percepción de la imagen en deportistas de gimnasia rítmica.

INTRODUCTION: Introduction: among adolescent gymnasts some concern for body weight has been observed, with diets inadequate in energy and some nutrients in the search for maximum performance. Objective: the aim of this study was to evaluate the dietary-nutritional status, body composition, eating behavior, and perceived body image concerns of female gymnasts at sub-national competition levels. In addition, to study the relationship between the prevalence of the risk of eating disorders and variables such as substance use, irregular menstruation, fatigue, and hours of sleep. Materials and method: a total of 33 female subelite gymnasts participated (age: M = 14.52, SD = 1.85), with age ranging from 11 to 18 years. Anthropometric evaluations (restricted profile) were made, the Eating Attitudes Test (EAT-26) and Body Shape Questionnaire (BSQ) were administered, and the subjects were then interviewed for collecting sociodemographic, socio-sports, health, and food intake data. Results: the results showed that their diet was deficient, among other micro- and macro-nutrients, in water, carbohydrates, proteins, vitamins D and E, fiber, iron and calcium, whereas they ingested an excess of vitamin A and sodium. These athletes had normal weight, high muscle mass values, low fat mass levels, and intermediate somatotype components (balanced endomorph with a tendency to central). Two cases at risk for an eating disorder, and concerns related to perceived body image in a quarter of the sample were identified. Conclusion: the risk of having an eating disorder is related to the consumption of prohibited drugs or addictive substances, irregular menstruation, tiredness, and fewer hours of sleep.

INTRODUCCIÓN: Introducción: entre las gimnastas adolescentes se ha observado cierta preocupación por el peso, con dietas insuficientes en energía y algunos nutrientes en búsqueda del máximo rendimiento. Esta preocupación puede estar relacionada con trastornos de la conducta alimentaria, menstruación irregular, cansancio y descanso insuficiente. Objetivos: evaluar el estado diétético-nutricional, la composición corporal, el comportamiento alimentario y la preocupación por la imagen corporal de las gimnastas de competición. Métodos: estudio observacional y transveral en el que participaron 33 gimnastas femeninas (edad: M = 14,52, DT = 1,85), subélite, de entre 11 y 18 años de edad. Se realizaron valoraciones antropométricas, se les aplicó un test de actitudes alimentarias (EAT-26) y un cuestionario sobre la figura corporal (BSQ), y se las entrevistó, recogiéndose datos sociodemográficos, sociodeportivos, de salud y sobre la ingesta. Resultados: la dieta de las deportistas es principalmente deficitaria en agua, carbohidratos, proteínas, vitaminas D y E, fibra, hierro y calcio, con sobreingesta de vitamina A y sodio. Las deportistas presentan normopeso y valores altos de masa muscular, bajos de masa grasa y medios de los componentes del somatotipo (endomorfo equilibrado con tendencia a central). Se detectaron dos casos de riesgo de trastorno de la conducta alimentaria (TCA) y preocupación por la imagen corporal percibida en un cuarto de la muestra. Conclusiones: el riesgo de padecer un TCA se relaciona con el consumo de fármacos prohibidos o sustancias adictivas, la menstruación irregular, el cansancio y dormir menos horas.

Type 2 diabetes remission: 2 year within-trial and lifetime-horizon cost-effectiveness of the Diabetes Remission Clinical Trial (DiRECT)/Counterweight-Plus weight management programme.

AIMS/HYPOTHESIS: Approximately 10% of total healthcare budgets worldwide are spent on treating diabetes and its complications, and budgets are increasing globally because of ageing populations and more expensive second-line medications. The aims of the study were to estimate the within-trial and lifetime cost-effectiveness of the weight management programme, which achieved 46% remissions of type 2 diabetes at year 1 and 36% at year 2 in the Diabetes Remission Clinical Trial (DiRECT). METHODS: Within-trial analysis assessed costs of the Counterweight-Plus intervention in DiRECT (including training, programme materials, practitioner appointments and low-energy diet), along with glucose-lowering and antihypertensive medications, and all routine healthcare contacts. Lifetime cost per quality-adjusted life-year (QALY) was estimated according to projected durations of remissions, assuming continued relapse rates as seen in year 2 of DiRECT and consequent life expectancy, quality of life and healthcare costs. RESULTS: Mean total 2 year healthcare costs for the intervention and control groups were £3036 and £2420, respectively: an incremental cost of £616 (95% CI -£45, £1269). Intervention costs (£1411; 95% CI £1308, £1511) were partially offset by lower other healthcare costs (£796; 95% CI £150, £1465), including reduced oral glucose-lowering medications by £231 (95% CI £148, £314). Net remission at 2 years was 32.3% (95% CI 23.5%, 40.3%), and cost per remission achieved was £1907 (lower 95% CI: intervention dominates; upper 95% CI: £4212). Over a lifetime horizon, the intervention was modelled to achieve a mean 0.06 (95% CI 0.04, 0.09) QALY gain for the DiRECT population and mean total lifetime cost savings per participant of £1337 (95% CI £674, £2081), with the intervention becoming cost-saving within 6 years. CONCLUSIONS/INTERPRETATION: Incorporating the lifetime healthcare cost savings due to periods of remission from diabetes and its complications, the DiRECT intervention is predicted to be both more effective (QALY gain) and cost-saving in adults with type 2 diabetes compared with standard care. This conclusion appears robust to various less favourable model scenarios, providing strong evidence that resources could be shifted cost-effectively to support achieving remissions with the DiRECT intervention. TRIAL REGISTRATION: ISRCTN03267836 Graphical abstract.

Health and Economic Impacts of the National Menu Calorie Labeling Law in the United States: A Microsimulation Study.

BACKGROUND: Excess caloric intake is linked to weight gain, obesity, and related diseases, including type 2 diabetes mellitus and cardiovascular disease (CVD). Obesity incidence is rising, with nearly 3 in 4 US adults being overweight or obese. In 2018, the US federal government finalized the implementation of mandatory labeling of calorie content on all menu items across major chain restaurants nationally as a strategy to support informed consumer choice, reduce caloric intake, and potentially encourage restaurant reformulations. Yet, the potential health and economic impacts of this policy remain unclear. METHODS AND RESULTS: We used a validated microsimulation model (CVD-PREDICT) to estimate reductions in CVD events, diabetes mellitus cases, gains in quality-adjusted life years, costs, and cost-effectiveness of the menu calorie labeling intervention, based on consumer responses alone, and further accounting for potential industry reformulation. The model incorporated nationally representative demographic and dietary data from National Health and Nutrition Examination Surveys 2009 to 2016; policy effects on consumer diets and body mass index-disease effects from published meta-analyses; and policy effects on industry reformulation, policy costs (policy administration, industry compliance, and reformulation), and health-related costs (formal and informal healthcare costs, productivity costs) from established sources or reasonable assumptions. We modeled change in calories to change in weight using an established dynamic weight-change model, assuming 50% of expected calorie reductions would translate to long-term reductions. Findings were evaluated over 5 years and a lifetime from healthcare and societal perspectives, with uncertainty incorporated in both 1-way and probabilistic sensitivity analyses. Between 2018 and 2023, implementation of the restaurant menu calorie labeling law was estimated, based on consumer response alone, to prevent 14 698 new CVD cases (including 1575 CVD deaths) and 21 522 new type 2 diabetes mellitus cases, gaining 8749 quality-adjusted life years. Over a lifetime, corresponding values were 135 781 new CVD cases (including 27 646 CVD deaths), 99 736 type 2 diabetes mellitus cases, and 367 450 quality-adjusted life years. Assuming modest restaurant item reformulation, both health and economic benefits were estimated to be about 2-fold larger than based on consumer response alone. The consumer response alone was estimated to be cost-saving by 2023, with net lifetime savings of $10.42B from a healthcare perspective and $12.71B from a societal perspective. Findings were robust in a range of sensitivity analyses. CONCLUSIONS: Our national model suggests that the full implementation of the US calorie menu labeling law will generate significant health gains and healthcare and societal cost-savings. Industry responses to modestly reformulate menu items would provide even larger additional benefits.

Effectiveness of Mediterranean Diet Implementation in Dry Eye Parameters: A Study of PREDIMED-PLUS Trial.

The purpose of this study is to evaluate the effect of a Mediterranean diet supplemented with extra virgin olive oil and nuts on dry eye parameters. The participants in this study were randomized into one of the two interventional arms: (1) a standard intervention group, a Mediterranean diet supplemented with extra virgin olive oil and nuts; and (2) an intensive intervention group, based on a hypocaloric Mediterranean diet and an intensive lifestyle program with physical activity and weight-loss goals. In both groups, common dry eye tests were conducted at baseline and after six months: the Ocular Surface Disease Index (OSDI), the Dry Eye Scoring System (DESS), tear break-up time (TBUT), the Schirmer's test, and the Oxford staining grade. Sixty-seven eyes were examined. After six months, dry eye parameters improved in both groups; differences between groups were favorable for the intensive intervention group. The implementation of a Mediterranean diet pattern was beneficial for the selected patients with dry eye, and could be beneficial for patients with dry eye in general. Behavioral support for diet adherence and the promotion of healthy lifestyles (exercise) and weight loss (calorie restriction) have an added positive effect.

Four Weeks of Time-Restricted Feeding Combined with Resistance Training Does Not Differentially Influence Measures of Body Composition, Muscle Performance, Resting Energy Expenditure, and Blood Biomarkers.

Recently, interest in time-restricted feeding (TRF) has increased from reports highlighting improvements in body composition and muscular performance measures. Twenty-six recreationally active males were randomly assigned to either TRF (n = 13; ~22.9 years; 82.0 kg; 178.1 cm; 8 h eating window, 25% caloric deficit, 1.8 g/kg/day protein) or normal diet (ND; n = 13; ~22.5 years; 83.3 kg; 177.5 cm; normal meal pattern; 25% caloric deficit, 1.8 g/kg/day protein) groups. Participants underwent 4-weeks of supervised full body resistance training. Changes in body composition (fat mass (FM), fat free mass (FFM), and body fat percentage (BF%)), skeletal muscle cross sectional area (CSA) and muscle thickness (MT) of the vastus lateralis (VL), rectus femoris, (RF), and biceps brachii (BB) muscles, resting energy expenditure (REE), muscular performance, blood biomarkers, and psychometric parameters were assessed. Significant (p < 0.05) decreases were noted in BM, FM, BF%, testosterone, adiponectin, and REE, along with significant increases in BP1RM, LP1RM, VJHT, VJPP, VLCSA, BBCSA, and BBMT in both groups. Plasma cortisol levels were significantly elevated at post (p = 0.018) only in ND. Additionally, FFM was maintained equally between groups. Thus, a TRF style of eating does not enhance reductions in FM over caloric restriction alone during a 4-week hypocaloric diet.

Low costs of adaptation to dietary restriction.

Dietary restriction (DR) is the most successful and widespread means of extending organismal lifespan. However, the evolutionary basis of life extension under DR remains uncertain. The traditional evolutionary explanation is that when organisms experience DR, they allocate endogenous resources to survival and postpone reproduction until conditions improve. However, this life-extension strategy should be maladaptive if DR continues for multiple generations due to trade-offs between longevity and reproduction. To test this prediction, we subjected the budding yeast Saccharomyces cerevisiae to 1800 generations of evolution on restricted versus non-restricted diets. Adaptation to a non-restricted diet improved reproductive fitness by 57%, but provided a much smaller (14%) advantage on a restricted diet. By contrast, adaptation to DR resulted in an approximately 35% increase in reproductive fitness on both restricted and non-restricted diets. Importantly, the life-extending effect of DR did not decrease following long-term evolution on the restricted diet. Thus, contrary to theoretical expectations, we found no evidence that the life-extending DR response became maladaptive during multigenerational DR. Together, our results suggest that the DR response has a low cost and that this phenomenon may have evolved as part of a generalist strategy that extends beyond the benefits of postponing reproduction.

The hidden costs of dietary restriction: Implications for its evolutionary and mechanistic origins.

Dietary restriction (DR) extends life span across taxa. Despite considerable research, universal mechanisms of DR have not been identified, limiting its translational potential. Guided by the conviction that DR evolved as an adaptive, pro-longevity physiological response to food scarcity, biomedical science has interpreted DR as an activator of pro-longevity molecular pathways. Current evolutionary theory predicts that organisms invest in their soma during DR, and thus when resource availability improves, should outcompete rich-fed controls in survival and/or reproduction. Testing this prediction in Drosophila melanogaster (N > 66,000 across 11 genotypes), our experiments revealed substantial, unexpected mortality costs when flies returned to a rich diet following DR. The physiological effects of DR should therefore not be interpreted as intrinsically pro-longevity, acting via somatic maintenance. We suggest DR could alternatively be considered an escape from costs incurred under nutrient-rich conditions, in addition to costs associated with DR.

Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice.

Intermittent fasting (IF), a dietary intervention involving periodic energy restriction, has been considered to provide numerous benefits and counteract metabolic abnormalities. So far, different types of IF models with varying durations of fasting and feeding periods have been documented. However, interpreting the outcomes is challenging, as many of these models involve multifactorial contributions from both time- and calorie-restriction strategies. For example, the alternate day fasting model, often used as a rodent IF regimen, can result in underfeeding, suggesting that health benefits from this intervention are likely mediated via both caloric restriction and fasting-refeeding cycles. Recently, it has been successfully demonstrated that 2:1 IF, comprising 1 day of fasting followed by 2 days of feeding, can provide protection against diet-induced obesity and metabolic improvements without a reduction in overall caloric intake. Presented here is a protocol of this isocaloric 2:1 IF intervention in mice. Also described is a pair-feeding (PF) protocol required to examine a mouse model with altered eating behaviors, such as hyperphagia. Using the 2:1 IF regimen, it is demonstrated that isocaloric IF leads to reduced body weight gain, improved glucose homeostasis, and elevated energy expenditure. Thus, this regimen may be useful to investigate the health impacts of IF on various disease conditions.