Time-Restricted Eating Without Calorie Counting for Weight Loss in a Racially Diverse Population : A Randomized Controlled Trial.

BACKGROUND: Time-restricted eating (TRE), without calorie counting, has become a popular weight loss strategy, yet long-term randomized trials evaluating its efficacy are limited. OBJECTIVE: To determine whether TRE is more effective for weight control and cardiometabolic risk reduction compared with calorie restriction (CR) or control. DESIGN: 12-month randomized controlled trial. (ClinicalTrials.gov: NCT04692532). SETTING: University of Illinois Chicago from January 2021 to September 2022. PARTICIPANTS: 90 adults with obesity. INTERVENTION: 8-hour TRE (eating between noon and 8:00 p.m. only, without calorie counting), CR (25% energy restriction daily), or control (eating over a period of 10 or more hours per day). Participants were not blinded. MEASUREMENTS: Change in body weight, metabolic markers, and energy intake by month 12. RESULTS: Seventy-seven persons completed the study. Mean age was 40 years (SD, 11), 33% were Black, and 46% were Hispanic. Mean reduction in energy intake was -425 kcal/d (SD, 531) for TRE and -405 kcal/d (SD, 712) for CR. Compared with the control group, weight loss by month 12 was -4.61 kg (95% CI, -7.37 to -1.85 kg; P ≤ 0.01) (-4.87% [CI, -7.61% to -2.13%]) for the TRE group and -5.42 kg (CI, -9.13 to -1.71 kg; P ≤ 0.01) (-5.30% [CI, -9.06% to -1.54%]) for the CR group, with no statistically significant difference between TRE and CR (0.81 kg [CI, -3.07 to 4.69 kg; P = 0.68]) (0.43% [CI, -3.48% to 4.34%]). LIMITATION: Not blinded, not powered to detect relatively large differences in weight loss, and lack of adjustment for multiple comparisons. CONCLUSION: Time-restricted eating is more effective in producing weight loss when compared with control but not more effective than CR in a racially diverse population. PRIMARY FUNDING SOURCE: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.

Effects of ketogenic diet on health outcomes: an umbrella review of meta-analyses of randomized clinical trials.

BACKGROUND: Systematic reviews and meta-analyses of randomized clinical trials (RCTs) have reported the benefits of ketogenic diets (KD) in various participants such as patients with epilepsy and adults with overweight or obesity. Nevertheless, there has been little synthesis of the strength and quality of this evidence in aggregate. METHODS: To grade the evidence from published meta-analyses of RCTs that assessed the association of KD, ketogenic low-carbohydrate high-fat diet (K-LCHF), and very low-calorie KD (VLCKD) with health outcomes, PubMed, EMBASE, Epistemonikos, and Cochrane database of systematic reviews were searched up to February 15, 2023. Meta-analyses of RCTs of KD were included. Meta-analyses were re-performed using a random-effects model. The quality of evidence per association provided in meta-analyses was rated by the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) criteria as high, moderate, low, and very low. RESULTS: We included 17 meta-analyses comprising 68 RCTs (median [interquartile range, IQR] sample size of 42 [20-104] participants and follow-up period of 13 [8-36] weeks) and 115 unique associations. There were 51 statistically significant associations (44%) of which four associations were supported by high-quality evidence (reduced triglyceride (n = 2), seizure frequency (n = 1) and increased low-density lipoprotein cholesterol (LDL-C) (n = 1)) and four associations supported by moderate-quality evidence (decrease in body weight, respiratory exchange ratio (RER), hemoglobin A1c, and increased total cholesterol). The remaining associations were supported by very low (26 associations) to low (17 associations) quality evidence. In overweight or obese adults, VLCKD was significantly associated with improvement in anthropometric and cardiometabolic outcomes without worsening muscle mass, LDL-C, and total cholesterol. K-LCHF was associated with reduced body weight and body fat percentage, but also reduced muscle mass in healthy participants. CONCLUSIONS: This umbrella review found beneficial associations of KD supported by moderate to high-quality evidence on seizure and several cardiometabolic parameters. However, KD was associated with a clinically meaningful increase in LDL-C. Clinical trials with long-term follow-up are warranted to investigate whether the short-term effects of KD will translate to beneficial effects on clinical outcomes such as cardiovascular events and mortality.

Effect of Dietary Sodium on Blood Pressure: A Crossover Trial.

Importance: Dietary sodium recommendations are debated partly due to variable blood pressure (BP) response to sodium intake. Furthermore, the BP effect of dietary sodium among individuals taking antihypertensive medications is understudied. Objectives: To examine the distribution of within-individual BP response to dietary sodium, the difference in BP between individuals allocated to consume a high- or low-sodium diet first, and whether these varied according to baseline BP and antihypertensive medication use. Design, Setting, and Participants: Prospectively allocated diet order with crossover in community-based participants enrolled between April 2021 and February 2023 in 2 US cities. A total of 213 individuals aged 50 to 75 years, including those with normotension (25%), controlled hypertension (20%), uncontrolled hypertension (31%), and untreated hypertension (25%), attended a baseline visit while consuming their usual diet, then completed 1-week high- and low-sodium diets. Intervention: High-sodium (approximately 2200 mg sodium added daily to usual diet) and low-sodium (approximately 500 mg daily total) diets. Main Outcomes and Measures: Average 24-hour ambulatory systolic and diastolic BP, mean arterial pressure, and pulse pressure. Results: Among the 213 participants who completed both high- and low-sodium diet visits, the median age was 61 years, 65% were female and 64% were Black. While consuming usual, high-sodium, and low-sodium diets, participants' median systolic BP measures were 125, 126, and 119 mm Hg, respectively. The median within-individual change in mean arterial pressure between high- and low-sodium diets was 4 mm Hg (IQR, 0-8 mm Hg; P < .001), which did not significantly differ by hypertension status. Compared with the high-sodium diet, the low-sodium diet induced a decline in mean arterial pressure in 73.4% of individuals. The commonly used threshold of a 5 mm Hg or greater decline in mean arterial pressure between a high-sodium and a low-sodium diet classified 46% of individuals as "salt sensitive." At the end of the first dietary intervention week, the mean systolic BP difference between individuals allocated to a high-sodium vs a low-sodium diet was 8 mm Hg (95% CI, 4-11 mm Hg; P < .001), which was mostly similar across subgroups of age, sex, race, hypertension, baseline BP, diabetes, and body mass index. Adverse events were mild, reported by 9.9% and 8.0% of individuals while consuming the high- and low-sodium diets, respectively. Conclusions and Relevance: Dietary sodium reduction significantly lowered BP in the majority of middle-aged to elderly adults. The decline in BP from a high- to low-sodium diet was independent of hypertension status and antihypertensive medication use, was generally consistent across subgroups, and did not result in excess adverse events. Trial Registration: ClinicalTrials.gov Identifier: NCT04258332.

Current research: effect of time restricted eating on weight and cardiometabolic health.

Intermittent fasting has grown in popularity as a weight loss strategy in recent years. In particular, time restricted eating (TRE) has been popularized in the diet industry with dozens of books touting its ability to promote weight loss and improve glucose regulation. TRE involves confining the eating window to a specified number of hours per day (usually 4-10 h), and fasting (with zero-calorie beverages) for the remaining hours of the day. While several studies of TRE have been performed in rodent models, human studies are only now emerging. The goal of this review is to summarize the effects of TRE on body weight and cardiometabolic disease risk factors in human subjects. Accumulating evidence shows that TRE may spontaneously decrease energy intake by 20-30% under ad libitum conditions, producing small but statistically significant weight loss of 1-4%. In addition, TRE may significantly decrease systolic and diastolic blood pressure independent of weight loss. Further, improvements in fasting insulin and insulin resistance have also been reported. Taken together, these preliminary data suggest that TRE produces mild weight loss, and also may improve some aspects of cardiometabolic health by lowering blood pressure and insulin resistance.

Time restricted eating for the prevention of type 2 diabetes.

Type 2 diabetes can potentially be prevented by targeted lifestyle and weight loss interventions. Time restricted eating (TRE) is a form of intermittent fasting that has emerged as a novel diet strategy to reduce body weight and improve glycaemic control. TRE involves eating within a certain window of time (usually 4 to 10 h), and water-fasting for the remaining hours of the day. The purpose of this review is to summarize the effects of TRE on body weight and markers of glycaemic control in human subjects. We also aim to provide mechanistic insights into the effect of TRE on insulin sensitivity and glucose tolerance. Results to date reveal that TRE produces mild weight loss (1%-4% from baseline) and energy restriction, when food consumption is restricted to 4-10 h/day. TRE also reduces fasting insulin and improves insulin sensitivity in individuals with prediabetes and those with obesity. Moreover, TRE improves glucose tolerance and decreases serum glucose excursions. The possible mechanisms underlying these benefits include increased autophagic flux, mild elevations in ketone bodies, a reduction in oxidative stress, and the stimulation of ß-cell responsiveness. While these preliminary results offer promise for the use of TRE in the prevention of type 2 diabetes, larger and longer-term human trials will be needed to confirm these findings.

Cardiometabolic Benefits of Intermittent Fasting.

This review aims to summarize the effects of intermittent fasting on markers of cardiometabolic health in humans. All forms of fasting reviewed here-alternate-day fasting (ADF), the 5:2 diet, and time-restricted eating (TRE)-produced mild to moderate weight loss (1-8% from baseline) and consistent reductions in energy intake (10-30% from baseline). These regimens may benefit cardiometabolic health by decreasing blood pressure, insulin resistance, and oxidative stress. Low-density lipoprotein cholesterol and triglyceride levels are also lowered, but findings are variable. Other health benefits, such as improved appetite regulation and favorable changes in the diversity of the gut microbiome, have also been demonstrated, but evidence for these effects is limited. Intermittent fasting is generally safe and does not result in energy level disturbances or increased disordered eating behaviors. In summary, intermittent fasting is a safe diet therapy that can produce clinically significant weight loss (>5%) and improve several markers of metabolic health in individuals with obesity.

The effect of 4-h versus 6-h time restricted feeding on sleep quality, duration, insomnia severity and obstructive sleep apnea in adults with obesity.

BACKGROUND: Time restricted feeding (TRF) involves deliberately restricting the times during which energy is ingested. Preliminary findings suggest that 8-10-h TRF improves sleep. However, the effects of shorter TRF windows (4-6 h) on sleep, remain unknown. AIMS: This study compared the effects of 4-h versus 6-h TRF on sleep quality, duration, insomnia severity and the risk of obstructive sleep apnea. METHODS: Adults with obesity (n = 49) were randomized into one of three groups: 4-h TRF (eating only between 3 and 7 p.m.), 6-h TRF (eating only between 1 and 7 p.m.), or a control group (no meal timing restrictions) for 8 weeks. RESULTS: After 8 weeks, body weight decreased (p < 0.001) similarly by 4-h TRF (-3.9 ± 0.4 kg) and 6-h TRF (-3.4 ± 0.4 kg), versus controls. Sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI), did not change by 4-h TRF (baseline: 5.9 ± 0.7; week 8: 4.8 ± 0.6) or 6-h TRF (baseline: 6.4 ± 0.8; week 8: 5.3 ± 0.9), versus controls. Wake time, bedtime, sleep duration and sleep onset latency also remained unchanged. Insomnia severity did not change by 4-h TRF (baseline: 4.4 ± 1.0; week 8: 4.7 ± 0.9) or 6-h TRF (baseline: 8.3 ± 1.2; week 8: 5.5 ± 1.1), versus controls. Percent of participants reporting obstructive sleep apnea symptoms did not change by 4-h TRF (baseline: 44%; week 8: 25%) or 6-h TRF (baseline: 47%; week 8: 20%), versus controls. CONCLUSION: These findings suggest that 4- and 6-h TRF have no effect on sleep quality, duration, insomnia severity, or the risk of obstructive sleep apnea.

Time-Restricted Eating to Improve Cardiovascular Health.

PURPOSE OF REVIEW: Time-restricted eating (TRE) is a form of intermittent fasting that involves confining the eating window to 4-10 h and fasting for the remaining hours of the day. The purpose of this review is to summarize the current literature pertaining to the effects of TRE on body weight and cardiovascular disease risk factors. RECENT FINDINGS: Human trial findings show that TRE reduces body weight by 1-4% after 1-16 weeks in individuals with obesity, relative to controls with no meal timing restrictions. This weight loss results from unintentional reductions in energy intake (~350-500 kcal/day) that occurs when participants confine their eating windows to 4-10 h/day. TRE is also effective in lowering fat mass, blood pressure, triglyceride levels, and markers of oxidative stress, versus controls. This fasting regimen is safe and produces few adverse events. These findings suggest that TRE is a safe diet therapy that produces mild reductions in body weight and also lowers several key indicators of cardiovascular disease in participants with obesity.

Does the weight loss efficacy of alternate day fasting differ according to sex and menopausal status?

BACKGROUND AND AIMS: This study examined if the weight loss and metabolic benefits of alternate day fasting (ADF) varies according to sex and menopausal status in adults with obesity. METHODS AND RESULTS: This secondary analysis pooled the data of men and women (n = 75) who participated in three 12-week ADF studies (500 kcal fast day; alternated with an ad libitum intake feast day). Body weight decreased in premenopausal women (-4.6 ± 3.2%), postmenopausal women (-6.5 ± 3.2%) and men (-6.2 ± 4.4%) (main effect of time, P < 0.001), with no difference between groups (no group × time interaction). Energy intake on fast days was higher than prescribed in all groups (∼400-500 excess kcal consumed), with no differences between groups. Fat mass, lean mass, fasting insulin, and insulin resistance, and blood pressure decreased similarly in all groups (main effect of time, P < 0.05 for all comparisons). LDL cholesterol decreased more in postmenopausal versus premenopausal women (group × time interaction, P = 0.01). Fasting glucose, HDL cholesterol, and triglycerides remained unchanged in all groups. CONCLUSION: These findings suggest that the weight loss and metabolic benefits of ADF do not generally vary according to sex or menopausal status in adults with obesity. TRIAL REGISTRATION: Clinicaltrials.gov, NCT00960505; NCT03528317.

Effect of time restricted feeding on the gut microbiome in adults with obesity: A pilot study.

BACKGROUND: Time restricted feeding is a form of intermittent fasting where participants shorten the daily window in which they eat. AIM: This is the first study to examine the effects of intermittent fasting on changes in the gut microbiome. METHODS: Adults with obesity (n = 14) participated in a daily 8-hour time restricted feeding intervention (8-hour feeding window/16-hour fasting window) for 12 weeks. Fecal microbiota were determined by 16 S rRNA (ribosomal ribonucleic acid) gene sequencing of stool samples. RESULTS: Body weight decreased (P < 0.05) by -2 ± 1 kg. Gut microbiota phylogenetic diversity remained unchanged. The two most common phyla were Firmicutes and Bacteroidetes accounting for 61.2% and 26.9% of total abundance at baseline. No significant alterations in the abundance of Firmicutes, Bacteroidetes, or any other phyla were detected after 12 weeks of time restricted feeding. CONCLUSIONS: Time restricted feeding did not significantly alter the diversity or overall composition of the gut microbiome.

Beverage intake during alternate-day fasting: Relationship to energy intake and body weight.

BACKGROUND: Alternate-day fasting (ADF) involves a 'famine day' (25% energy intake) and a 'feast day' (ad libitum intake). This secondary analysis examined changes in beverage intake in relation to energy intake and body weight during 12 months of ADF versus daily calorie restriction (CR). METHODS: Obese subjects (n = 100 enrolled, n = 69 completers) were randomized to one of three groups for 12 months: (a) ADF; (b) CR; or (c) control. RESULTS: At baseline, intakes of diet soda, caffeinated beverages, sugar-sweetened soda, alcohol, juice, and milk were similar between groups. There were no statistically significant changes in the intake of these beverages by month 6 or 12 between ADF (feast or famine day), CR, or control groups. Beverage intake was not related to energy intake or body weight at month 6 or 12 in any group. CONCLUSION: These pilot findings suggest that intermittent fasting does not impact beverage intake in a way that affects energy intake or body weight.

Long term (4 years) improved insulin sensitivity following islet cell transplant in type 1 diabetes.

BACKGROUND: Impaired insulin sensitivity (IS) predicts complications and mortality in type 1 diabetes (T1D). Insulin sensitivity improves shortly after islet cell transplant for T1D, yet long-term changes in IS and associated factors such as patient characteristics, transplant factors, clinical management, and IS-related biomarkers are unknown. METHODS: Up to 9 years (mean 4) of longitudinal data were available on 22 adults (18 female) with T1D who received 1 to 3 transplants in Phase 1/2 or 3 clinical trials (2004-2014). Metabolic testing posttransplant estimated IS by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR; 111 observations) and the Simple Index of Insulin Sensitivity (SIis ; 95 observations). RESULTS: Simple Index of Insulin Sensitivity significantly increased the first year posttransplant (P = .02), then stabilized (P = .39); HOMA-IR remained stable posttransplant (P = .92). Adjusting for age and BMI, higher SIis was associated with lower HbA1c following transplant (P = .03). Greater IS as measured by lower HOMA-IR and higher SIis was associated with lower fasting C-peptide (both P ≤ .04) and also with higher exenatide dose (both P ≤ .01). More islets transplanted were associated with higher SIis (P < .0001). Lower leptin at transplant predicted lower HOMA-IR and higher SIis after transplant, and lower bone marker receptor activator of nuclear factor kappa-B ligand predicted lower HOMA-IR (all P ≤ .01). CONCLUSIONS: Insulin sensitivity measured by SIis was improved several years following transplant, while IS measured by HOMA-IR did not worsen. Higher exenatide dose, more islets transplanted, and diet and exercise (lowering leptin and receptor activator of nuclear factor kappa-B ligand) may improve IS, which may enhance glycaemic control and lower metabolic demand on transplanted islets. Long-term clamp studies are needed to confirm these results.

Eating behavior traits of successful weight losers during 12 months of alternate-day fasting: An exploratory analysis of a randomized controlled trial.

BACKGROUND: Alternate-day fasting (ADF) has gained popularity in recent years. The diet consists of a "fast day" where an individual consumes 0-25% of their energy needs, alternated with a "feast day" where a person is permitted to eat ad libitum. AIM: This study examined eating behavior traits of successful weight losers during alternate day fasting. METHODS: Obese participants ( n = 34) took part in 12 months of ADF and were grouped into a high (≥5%) or low-weight-loss (<5%) group post-treatment. RESULTS: The high-weight-loss group demonstrated increased ( p = 0.04) fullness, decreased ( p = 0.03) hunger, increased dietary protein intake (15% to 20% of kcal, p = 0.04), and better adherence to fast-day calorie goals. CONCLUSIONS: Thus, individuals who achieve clinically significant weight loss with ADF demonstrate improved satiety, increased protein intake, and better adherence to fast-day calorie goals.

Coronary artery calcium may stabilize following islet cell transplantation in patients with type 1 diabetes.

Islet cell transplantation can functionally cure type 1 diabetes and also improve carotid intima-media thickness. This study provides a preliminary description of changes in coronary artery calcium following islet transplantation, and associated factors. Coronary artery calcium was measured in 14 patients with type 1 diabetes (11 had measures both pre- and post-transplant [mean 2.3 years]) in the University of Illinois at Chicago's clinical trial. Multivariable mixed-effects linear regression of repeated measures was used to quantify calcium change and determine if this change was longitudinally associated with risk/protective factors. Thirteen of the patients were female, with mean baseline age, diabetes duration, and BMI of 47.6 and 28.7 years, and 23.1, respectively. Over half (57%) had detectable coronary artery calcium pre-transplant. Minimal change (0.39 mm3 /y, P = .02) occurred in coronary artery calcium levels pre- to post-transplant. No patient met criteria for calcium progression. Coronary artery calcium was positively associated with total and small VLDL particles (P ≤ .02), statin dose (P = .02), and urine albumin-to-creatinine ratio (P = .04) and negatively associated with free fatty acids (P = .03), total HDL (P = .03), large HDL particles (P = .005), and tacrolimus dose (P = .02). Islet transplant may stabilize coronary artery calcium, with optimal management of lipids and kidney function remaining key therapeutic targets. [NCT00679041].

Meal frequency and timing in health and disease.

Although major research efforts have focused on how specific components of foodstuffs affect health, relatively little is known about a more fundamental aspect of diet, the frequency and circadian timing of meals, and potential benefits of intermittent periods with no or very low energy intakes. The most common eating pattern in modern societies, three meals plus snacks every day, is abnormal from an evolutionary perspective. Emerging findings from studies of animal models and human subjects suggest that intermittent energy restriction periods of as little as 16 h can improve health indicators and counteract disease processes. The mechanisms involve a metabolic shift to fat metabolism and ketone production, and stimulation of adaptive cellular stress responses that prevent and repair molecular damage. As data on the optimal frequency and timing of meals crystalizes, it will be critical to develop strategies to incorporate those eating patterns into health care policy and practice, and the lifestyles of the population.

Impact of intermittent fasting on glucose homeostasis.

PURPOSE OF REVIEW: This article provides an overview of the most recent human trials that have examined the impact of intermittent fasting on glucose homeostasis. RECENT FINDINGS: Our literature search retrieved one human trial of alternate day fasting, and three trials of Ramadan fasting published in the past 12 months. Current evidence suggests that 8 weeks of alternate day fasting that produces mild weight loss (4% from baseline) has no effect on glucose homeostasis. As for Ramadan fasting, decreases in fasting glucose, insulin, and insulin resistance have been noted after 4 weeks in healthy normal weight individuals with mild weight loss (1-2% from baseline). However, Ramadan fasting may have little impact on glucoregulatory parameters in women with polycystic ovarian syndrome who failed to observe weight loss. SUMMARY: Whether intermittent fasting is an effective means of regulating glucose homeostasis remains unclear because of the scarcity of studies in this area. Large-scale, longer-term randomized controlled trials will be required before the use of fasting can be recommended for the prevention and treatment of metabolic diseases.

Oxytocin levels are lower in premenopausal women with type 1 diabetes mellitus compared with matched controls.

BACKGROUND: Oxytocin, a hormone most commonly associated with parturition and lactation, may have additional roles in diabetes complications. We determined oxytocin levels in premenopausal women with type 1 diabetes mellitus (T1DM) compared with non-diabetic controls and examined associations of oxytocin with health behaviours, clinical factors, biomarkers, kidney function and bone health. Lower oxytocin was hypothesized for T1DM. METHODS: A cross-sectional study of premenopausal women with T1DM (n = 88) from the Wisconsin Diabetes Registry Study, a population-based cohort of incident T1DM cases, and matched non-diabetic controls (n = 74) was conducted. RESULTS: Women with T1DM had lower oxytocin levels than controls adjusting for caffeine and alcohol use (p = 0.03). Health behaviours associated with oxytocin differed between women with and without T1DM: oxytocin was negatively associated with hormonal contraceptive use (quantified as lifetime contraceptive oestrogen exposure) in women with T1DM (p = 0.003), whereas positively related to hormonal contraceptive use (quantified as never/former/current) in controls (p < 0.001). Oxytocin had a positive association with adiposity (waist-to-hip ratio and leptin) in women with T1DM and a negative relationship with adiposity (weight gain) in controls. In T1DM only, oxytocin was positively associated with caffeine intake (p = 0.01) and negatively associated with alcohol use (p = 0.01). Oxytocin was not related to glycemic control, kidney function or bone health in T1DM. CONCLUSIONS: Oxytocin levels are lower in women with T1DM than matched controls. Oxytocin also has opposing associations with hormonal contraceptives and adiposity in women with and without T1DM. Research is needed to determine if the altered oxytocin milieu in T1DM is associated with oxytocinher health outcomes.

Veganism Is a Viable Alternative to Conventional Diet Therapy for Improving Blood Lipids and Glycemic Control.

The American Diabetes Association (ADA) and the National Cholesterol Education Program (NCEP) have each outlined a set of dietary recommendations aimed at improving glycemic control and blood lipids, respectively. However, traditional vegan diets (low-fat diets that proscribe animal product consumption) are also effective at improving glycemic control, and dietary portfolios (vegan diets that contain prescribed amounts of plant sterols, viscous fibers, soy protein, and nuts) are also effective at improving blood lipids. The purpose of this review was to compare the effects of traditional vegan diets and dietary portfolios with ADA and NCEP diets on body weight, blood lipids, blood pressure, and glycemic control. The main findings are that traditional vegan diets appear to improve glycemic control better than ADA diets in individuals with type 2 diabetes mellitus (T2DM), while dietary portfolios have been consistently shown to improve blood lipids better than NCEP diets in hypercholesterolemic individuals.