Early time-restricted eating affects weight, metabolic health, mood, and sleep in adherent completers: A secondary analysis.

OBJECTIVE: Data are mixed on whether intermittent fasting improves weight loss and cardiometabolic health. Here, the effects of time-restricted eating (TRE) in participants who consistently adhered ≥5 d/wk every week were analyzed. METHODS: Ninety patients aged 25 to 75 years old with obesity were randomized to early TRE (eTRE; 8-hour eating window from 07:00 to 15:00) or a control schedule (≥12-hour window) for 14 weeks. A per-protocol analysis of weight loss, body composition, cardiometabolic health, and other end points was performed. RESULTS: Participants who adhered to eTRE ≥5 d/wk every week had greater improvements in body weight (-3.7 ± 1.2 kg; p = 0.003), body fat (-2.8 ± 1.3 kg; p = 0.04), heart rate (-7 ± 3 beats/min; p = 0.02), insulin resistance (-2.80 ± 1.36; p = 0.047), and glucose (-9 ± 5 mg/dL; p = 0.047) relative to adherers in the control group. They also experienced greater improvements in mood, including fatigue and anger; however, they self-reported sleeping less and taking longer to fall asleep. CONCLUSIONS: For those who can consistently adhere at least 5 d/wk, eTRE is a valuable approach for improving body weight, body fat, cardiometabolic health, and mood. Further research is needed to determine whether eTRE's effects of shortening sleep but reducing fatigue are healthful or not.

Impact of early time-restricted eating on diet quality, meal frequency, appetite, and eating behaviors: A randomized trial.

OBJECTIVE: Time-restricted eating (TRE) can reduce body weight, but it is unclear how it influences dietary patterns and behavior. Therefore, this study assessed the effects of TRE on diet quality, appetite, and several eating behaviors. METHODS: Adults with obesity were randomized to early TRE plus energy restriction (eTRE + ER; 8-hour eating window from 7:00 a.m. to 3:00 p.m.) or a control eating schedule plus energy restriction (CON + ER; ≥12-hour window) for 14 weeks. Food intake was assessed via the Remote Food Photography Method, while eating patterns, appetite, and eating behaviors were assessed via questionnaires. RESULTS: A total of 59 participants completed the trial, of whom 45 had valid food records. eTRE + ER did not affect eating frequency, eating restraint, emotional eating, or the consistency of mealtimes relative to CON + ER. eTRE + ER also did not affect overall diet quality. The intensity and frequency of hunger and fullness were similar between groups, although the eTRE + ER group was hungrier while fasting. CONCLUSIONS: When combined with a weight-loss program, eTRE does not affect diet quality, meal frequency, eating restraint, emotional eating, or other eating behaviors relative to eating over more than a 12-hour window. Rather, participants implement eTRE as a simple timing rule by condensing their normal eating patterns into a smaller eating window.

Effectiveness of Early Time-Restricted Eating for Weight Loss, Fat Loss, and Cardiometabolic Health in Adults With Obesity: A Randomized Clinical Trial.

Importance: It is unclear how effective intermittent fasting is for losing weight and body fat, and the effects may depend on the timing of the eating window. This randomized trial compared time-restricted eating (TRE) with eating over a period of 12 or more hours while matching weight-loss counseling across groups. Objective: To determine whether practicing TRE by eating early in the day (eTRE) is more effective for weight loss, fat loss, and cardiometabolic health than eating over a period of 12 or more hours. Design, Setting, and Participants: The study was a 14-week, parallel-arm, randomized clinical trial conducted between August 2018 and April 2020. Participants were adults aged 25 to 75 years with obesity and who received weight-loss treatment through the Weight Loss Medicine Clinic at the University of Alabama at Birmingham Hospital. Interventions: All participants received weight-loss treatment (energy restriction [ER]) and were randomized to eTRE plus ER (8-hour eating window from 7:00 to 15:00) or control eating (CON) plus ER (≥12-hour window). Main Outcomes and Measures: The co-primary outcomes were weight loss and fat loss. Secondary outcomes included blood pressure, heart rate, glucose levels, insulin levels, and plasma lipid levels. Results: Ninety participants were enrolled (mean [SD] body mass index, 39.6 [6.7]; age, 43 [11] years; 72 [80%] female). The eTRE+ER group adhered 6.0 (0.8) days per week. The eTRE+ER intervention was more effective for losing weight (-2.3 kg; 95% CI, -3.7 to -0.9 kg; P = .002) but did not affect body fat (-1.4 kg; 95% CI, -2.9 to 0.2 kg; P = .09) or the ratio of fat loss to weight loss (-4.2%; 95% CI, -14.9 to 6.5%; P = .43). The effects of eTRE+ER were equivalent to reducing calorie intake by an additional 214 kcal/d. The eTRE+ER intervention also improved diastolic blood pressure (-4 mm Hg; 95% CI, -8 to 0 mm Hg; P = .04) and mood disturbances, including fatigue-inertia, vigor-activity, and depression-dejection. All other cardiometabolic risk factors, food intake, physical activity, and sleep outcomes were similar between groups. In a secondary analysis of 59 completers, eTRE+ER was also more effective for losing body fat and trunk fat than CON+ER. Conclusions and Relevance: In this randomized clinical trial, eTRE was more effective for losing weight and improving diastolic blood pressure and mood than eating over a window of 12 or more hours at 14 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT03459703.

Almond protects the liver in coronary artery disease: A randomized controlled clinical trial.

OBJECTIVE: To compare the effect of Pakistani and American almonds on serum concentration of liver enzymes in coronary artery disease patients. METHODS: The randomised controlled trial was conducted at the Cardiology Clinics of Aga Khan University Hospital, Karachi, from February to July, 2012, and comprised patients who were randomised into intervention PA and AA groups and the control NI groups. Subjects in the intervention groups were provided Pakistani and American varieties of almonds 10g/day respectively with instructions to soak them overnight, remove the skin and eat them before breakfast for 12 weeks. The control group underwent no intervention. Serum concentrations of aspartate transaminase, Alanine transaminase and gamma-glutamyl transferase were analysed and compared. RESULTS: Of the 150 subjects, 110(73.3%) completed the study. Of them, there were 38(34.5%) in PA group, 41(37.3%) in AA, and 31(28.2%) in the NI group. Dietary almonds significantly reduced serum concentrations of aspartate transaminase, alanine transaminase and gamma-glutamyl transferase in the two intervention groups compared to the controls group (p<0.05) at 12-week follow-up. CONCLUSIONS: A low dose of almonds was found to be an effective strategy to protect the liver.

Early Detection and Prevention of Alzheimer's Disease: Role of Oxidative Markers and Natural Antioxidants.

Oxidative stress (OS) contributes to Alzheimer's disease (AD) pathology. OS can be a result of increased reactive oxygen/nitrogen species, reduced antioxidants, oxidatively damaged molecules, and/or a combination of these factors. Scientific literature is scarce for the markers of OS-specific for detecting AD at an early stage. The first aim of the current review is to provide an overview of the potential OS markers in the brain, cerebrospinal fluid (CSF), blood and/or urine that can be used for early diagnosis of human AD. The reason for exploring OS markers is that the proposed antioxidant therapies against AD appear to start too late to be effective. The second aim is to evaluate the evidence for natural antioxidants currently proposed to prevent or treat AD symptoms. To address these two aims, we critically evaluated the studies on humans in which various OS markers for detecting AD at an early stage were presented. Non-invasive OS markers that can detect mild cognitive impairment (MCI) and AD at an early stage in humans with greater specificity and sensitivity are primarily related to lipid peroxidation. However, a combination of OS markers, family history, and other biochemical tests are needed to detect the disease early on. We also report that the long-term use of vitamins (vitamin E as in almonds) and polyphenol-rich foods (curcumin/curcuminoids of turmeric, ginkgo biloba, epigallocatechin-3-gallate in green tea) seem justified for ameliorating AD symptoms. Future research on humans is warranted to justify the use of natural antioxidants.

Edible Nuts for Memory.

Nuts hold prime significance throughout the world as they offer multiple health benefits owing to their highly nutritious profile. A number of scientific studies have demonstrated their actions against inflammation, oxidative damage, the aging process, as well as dementia or memory loss. However, only walnuts, followed by almonds, hazelnuts and pistachios, have shown promising results in empirical studies for memory improvements. So, the current review focuses on presenting hypotheses regarding anti-dementia property of nine different nuts: almond, walnut, pistachio, Brazil nut, peanut, pecans, cashew, hazelnut, and chestnut. The nutritious profile of nuts contains essential fats (mostly mono- and poly-unsaturated fatty acids), proteins (source for arginine, lysine and tryptophan), vitamins (riboflavin, folate, and various tocopherols), fibers, minerals (calcium, sodium, magnesium, phosphorus and potassium) and trace elements (copper, zinc, and selenium). Interestingly, the constituents of natural products, nuts being an excellent example, work synergistically and/or in a side-effect neutralizing manner. These latter properties can make nuts an alternate therapy for humankind to fight against memory loss.

Impact of Intermittent Fasting on Lipid Profile-A Quasi-Randomized Clinical Trial.

Background: Sub-optimal HDL is a prognostic marker of cardiovascular disease. South Asia has a high prevalence of sub-optimal HDL compared to other parts of the world. Intermittent fasting (IF) is a type of energy restriction which may improve serum HDL and other lipids thereby reducing the risk of cardiovascular diseases. Objective: The aim of the study was to evaluate the effect of IF on lipid profile and HDL-cholesterol in a sample of South Asian adults. Methods: A 6-week quasi-experimental (non-randomized) clinical trial was conducted on participants with low HDL (< 40 mg/dl for men and < 50 mg/dl for women). Participants of the control group were recommended not to change their diet. The intervention group was recommended to fast for ~12 h during day time, three times per week for 6 weeks. Pulse rate, blood pressure, body weight, waist circumference, serum lipid profile, and blood glucose levels were measured at baseline and after 6 weeks. Result: A total of 40 participants were enrolled in the study (N = 20 in each group), while 35 (20 control and 15 intervention) completed the trial and were included in data analysis of the study. Body measurements, including body weight, BMI and waist circumference, showed significant interaction effects (p's < 0.001), indicating that there were larger reductions in the IF group than in the control group. Significant interaction effects were also observed for total (p = 0.033), HDL (p = 0.0001), and LDL cholesterol (p = 0.010) with larger improvements in the IF group. Conclusion: This study suggests that intermittent fasting may protect cardiovascular health by improving the lipid profile and raising the sub-optimal HDL. Intermittent fasting may be adopted as a lifestyle intervention for the prevention, management and treatment of cardiovascular disorders. Clinical Trial Registration: NCT03805776, registered on January 16, 2019, https://clinicaltrials.gov/ct2/show/NCT03805776.

An Intensive Lifestyle Intervention to Treat Type 2 Diabetes in the Republic of the Marshall Islands: Protocol for a Randomized Controlled Trial.

Background: The Republic of the Marshall Islands has the highest prevalence of type 2 diabetes (T2D) in the world, with the country's rapid rise of T2D attributed to its reliance on imported and refined foods laden with salt, sugar, and fat. As much as lifestyle factors can increase the risk of T2D, they can also reverse or treat the disease, with multiple studies demonstrating that plant-based diets and/or moderate exercise improve glycemic control and cardiovascular risk factors in T2D patients. Objective: We therefore tested the hypothesis that a community-based, intensive, plant-rich lifestyle intervention with exercise is more effective for treating and managing T2D in the Republic of the Marshall Islands than the standard of diabetes care. Methods: Building on a successful lifestyle program used at the Guam Seventh-day Adventist Clinic, we conducted a randomized controlled trial to test the effectiveness of an intensive lifestyle intervention involving a plant-rich diet and moderate exercise or the standard of care in T2D patients for 24 weeks. In this manuscript, we describe the clinical trial protocol, including the rationale, design, and methods of the clinical trial and the lifestyle program. The lifestyle intervention included a step-wise, intensive 12-week program of counseling and instruction on healthy eating, exercise, and stress management. The prescribed diet focused on high-fiber, whole plant foods, with foods grouped into a four-tiered system. The lifestyle intervention also involved hands-on cooking classes, meals prepared for participants, and group exercise classes-all tailored to be culturally appropriate. The study's main endpoints were glycemic control and cardiovascular disease risk factors. Discussion: The present study is the first randomized clinical trial conducted in the Republic of the Marshall Islands and the first lifestyle intervention trial conducted in Micronesia. The results of this study will help guide future medical care for indigenous populations in the Pacific Islands and will also shed light on how to effectively design and deliver intensive lifestyle interventions to treat and manage diabetes. Clinical Trials Registration: www.ClinicalTrials.gov; identifier NCT03862963.

Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans.

Time-restricted feeding (TRF) is a form of intermittent fasting that involves having a longer daily fasting period. Preliminary studies report that TRF improves cardiometabolic health in rodents and humans. Here, we performed the first study to determine how TRF affects gene expression, circulating hormones, and diurnal patterns in cardiometabolic risk factors in humans. Eleven overweight adults participated in a 4-day randomized crossover study where they ate between 8 am and 2 pm (early TRF (eTRF)) and between 8 am and 8 pm (control schedule). Participants underwent continuous glucose monitoring, and blood was drawn to assess cardiometabolic risk factors, hormones, and gene expression in whole blood cells. Relative to the control schedule, eTRF decreased mean 24-hour glucose levels by 4 ± 1 mg/dl (p = 0.0003) and glycemic excursions by 12 ± 3 mg/dl (p = 0.001). In the morning before breakfast, eTRF increased ketones, cholesterol, and the expression of the stress response and aging gene SIRT1 and the autophagy gene LC3A (all p < 0.04), while in the evening, it tended to increase brain-derived neurotropic factor (BNDF; p = 0.10) and also increased the expression of MTOR (p = 0.007), a major nutrient-sensing protein that regulates cell growth. eTRF also altered the diurnal patterns in cortisol and the expression of several circadian clock genes (p < 0.05). eTRF improves 24-hour glucose levels, alters lipid metabolism and circadian clock gene expression, and may also increase autophagy and have anti-aging effects in humans.

Studies on antioxidant, hepatoprotective, and vasculoprotective potential of Viola odorata and Wrightia tinctoria.

We have reported the antidyslipidemic, antihypertensive, and Ca++ channel blocking activities of Viola odorata (VO) and Wrightia tinctoria (WT). This study extends our understanding of their therapeutic potential by exploring the effects on biomarkers of hepatic and vascular dysfunction together with phytochemical standardization and antioxidant potential. Total phenolic compounds, total flavonoids content, and proanthocyanins of the methanolic extracts were identified using HPLC. Antioxidant capacity was measured using the in vitro assays. Two studies of 6-week duration were conducted on a high-fat diet rat model to test the leaves and seed extracts of VO and WT (300 and 600 mg/kg) for their effect on biomarkers for hepatic and vascular dysfunction. The HPLC analysis showed high contents of total phenolic compounds, total flavonoids content, and proanthocyanins along with distinctive phenolic composition. Both extracts exhibited significant antioxidant potential in 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), fluorescence recovery after photobleaching, and total antioxidant capacity (TAC) assays, comparable with synthetic standard antioxidants. The in vivo studies indicated a significant reduction in the high-fat-diet-induced rise in serum uric acid, phosphorus, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase. This study indicates the potential of VO and WT to protect from vascular and hepatic damage and an antioxidant effect, thus making these herbs strong candidates for managing cardiometabolic disorders.

Circadian regulation of glucose, lipid, and energy metabolism in humans.

The circadian system orchestrates metabolism in daily 24-hour cycles. Such rhythms organize metabolism by temporally separating opposing metabolic processes and by anticipating recurring feeding-fasting cycles to increase metabolic efficiency. Although animal studies demonstrate that the circadian system plays a pervasive role in regulating metabolism, it is unclear how, and to what degree, circadian research in rodents translates into humans. Here, we review evidence that the circadian system regulates glucose, lipid, and energy metabolism in humans. Using a range of experimental protocols, studies in humans report circadian rhythms in glucose, insulin, glucose tolerance, lipid levels, energy expenditure, and appetite. Several of these rhythms peak in the biological morning or around noon, implicating earlier in the daytime is optimal for food intake. Importantly, disruptions in these rhythms impair metabolism and influence the pathogenesis of metabolic diseases. We therefore also review evidence that circadian misalignment induced by mistimed light exposure, sleep, or food intake adversely affects metabolic health in humans. These interconnections among the circadian system, metabolism, and behavior underscore the importance of chronobiology for preventing and treating type 2 diabetes, obesity, and hyperlipidemia.

Almond supplementation reduces serum uric acid in coronary artery disease patients: a randomized controlled trial.

OBJECTIVE: Elevated serum uric acid (UA), a biomarker of renal insufficiency, is also an independent prognostic marker for morbidity in coronary artery disease (CAD) and poses serious health risks. This study reports the effect of almond consumption on UA in CAD patients. STUDY DESIGN: A randomized controlled clinical trial was conducted with three groups: no-intervention (NI), Pakistani almonds (PA) or American almonds (AA). Patients were recruited from the Cardiology Clinics, Aga Khan University Hospital. Two follow-ups were scheduled at week-6 and week-12. 150 patients were randomly divided in three groups (50 per group). NI was not given almonds, whereas the PA and AA were given Pakistani and American almond varieties (10 g/day), respectively; with instruction to soak overnight and eat before breakfast. RESULTS: Almonds supplementation significantly reduced (p < 0.05) serum UA among groups, and over time. At week-6, UA concentrations were -13 to -16 % less in PA and AA; at week-12 the concentrations were -14 to -18 % less, compared to NI. Systolic and diastolic blood pressure and body weights of the participants remained fairly constant among all the groups. CONCLUSION: Almonds (10 g/day), eaten before breakfast, reduces serum UA in CAD patients. Prevention of hyperuricemia can confer protection from kidney and vascular damage and if extrapolated for general population, dietary almonds can offer grander health benefit. Trial is registered at Australian New Zealand Clinical trial registry as ACTRN12614000036617.

Dietary Almonds Increase Serum HDL Cholesterol in Coronary Artery Disease Patients in a Randomized Controlled Trial.

BACKGROUND: More than one-half of coronary artery disease (CAD) patients have low HDL cholesterol despite having well-managed LDL cholesterol. Almond supplementation has not been shown to elevate circulating HDL cholesterol concentrations in clinical trials, perhaps because the baseline HDL cholesterol of trial subjects was not low. OBJECTIVE: This clinical trial was designed to test the effect of almond supplementation on low HDL cholesterol in CAD patients. METHODS: A total of 150 CAD patients (50 per group), with serum LDL cholesterol ≤100 mg/dL and HDL cholesterol ≤40 mg/dL in men and ≤50 mg/dL in women, were recruited from the Aga Khan University Hospital. After recording vital signs and completing a dietary and physical activity questionnaire, patients were randomly assigned to 1 of the following 3 groups: the no-intervention group (NI), the Pakistani almonds group (PA), and the American almonds group (AA). The respective almond varieties (10 g/d) were given to patients with instructions to soak them overnight, remove the skin, and eat them before breakfast. Blood samples for lipid profiling, body weight, and blood pressure were collected, and assessment of dietary patterns was done at baseline, week 6, and week 12. RESULTS: Almonds significantly increased HDL cholesterol. At weeks 6 and 12, HDL cholesterol was 12-14% and 14-16% higher, respectively, in the PA and AA than their respective baselines. In line with previous reports, serum concentrations of total cholesterol, triglycerides, LDL cholesterol, and VLDL cholesterol; total-to-HDL and LDL-to-HDL cholesterol ratios, and the atherogenic index were reduced in both the PA and AA at weeks 6 and 12 compared with baseline (P < 0.05). Effects on serum lipids did not differ between the 2 almond groups. Dietary patterns, body weight, and blood pressure did not change in any of the 3 groups during the trial. CONCLUSION: A low dose of almonds (10 g/d) consumed before breakfast can increase HDL cholesterol, in addition to improving other markers of abnormal lipid metabolism in CAD patients with low initial HDL cholesterol. This trial was registered at the Australian New Zealand Clinical Trial Registry as ACTRN12614000036617.

Cholesterol-cholate-butterfat diet offers multi-organ dysfunction in rats.

BACKGROUND: Comparable to commercial expensive high-fat diets, cholesterol-cholate-butterfat (CCB) diet has also been used to induce hyperlipidemia in rats. Our objective was to explore its influence on multiple organs. Consequence of fasting was also analysed. METHODS: Rats in groups 1 and 2 received normal diet (ND) whereas groups 3 and 4 received CCB-diet. Food was withdrawn daily for two hours from groups 2 (ND-F) and 4 (CCB-F). Blood was collected at fourth and sixth week for biochemical estimation; Morris water maze was done in the sixth week for learning ability and memory; after which aortae were isolated for vascular reactivity. RESULTS: Apart from hyperlipidemia, CCB also induced hyperglycemia with marked increase in hepatic enzymes: gamma-glutamyl transferase (GGT), alanine and aspartate aminotransferase (ALT and AST); and vascular biomarkers: uric acid (UA), phosphorus and alkaline phosphatase (ALP). Isolated aortae, pre-contracted with phenylephrine, were less responsive to acetylcholine indicating endothelial dysfunction--serum nitric oxide (NO) production was limited with subsequent inhibition of endothelial NO synthase. CCB diet also compromised learning ability. CCB-coupled fasting potentiated hyperlipidemia but prevented memory-loss. CONCLUSION: We introduce CCB-diet for multi-organ dysfunction in rats, and propose its use for research on cardiovascular diseases and associated manifestations involving immense interplay of integrated pathways.

Almonds inhibit dyslipidemia and vascular dysfunction in rats through multiple pathways.

BACKGROUND: Almonds are reported to be protective against cardiovascular diseases (CVDs); however, the possible mode of action has only infrequently been explored. OBJECTIVE: This study aimed at investigating the mechanistic basis for the benefits of almonds in atherosclerotic CVDs. METHODS: Three studies in 3 groups of rats were designed with the use of tyloxapol (study 1), a high-fat diet (HFD; study 2), and white-flour fructose (WFF; study 3). In each of the studies, the first group acted as the control [administered saline in study 1 and fed a normal diet (ND) in studies 2 and 3]; the second and third groups were treated with tyloxapol in study 1, an HFD in study 2, and WFF in study 3. The third group in each study was also fed almonds (3 g/kg) for 4 wk, after which blood was collected for biochemical evaluation. Livers and aortas were isolated from the rats in studies 1 and 2 for enzyme assays and vascular analysis, respectively. RESULTS: Almond supplementation significantly (P < 0.05) prevented hyperlipidemia in all of the rat models. Supplementation suppressed cholesterol synthesis, leading to a 65% inhibition of tyloxapol-induced activation of hepatic ß-hydroxy-ß-methylglutaryl coenzyme A reductase. The almond intervention inhibited by 56% the HFD-induced increase in serum concentrations of hepatic aminotransferases. Almonds also protected against an HFD-induced increase in uric acid (0.9-fold), phosphorus (1.1-fold), alkaline phosphatase (4.6-fold), and γ-glutamyltransferase (1-fold), with resultant concentrations that were not different from those in ND-fed rats (P > 0.05). Almonds partially restored the vascular reactivity of isolated aortas and prevented HFD-induced endothelial dysfunction by reducing inhibition of endothelial nitric oxide (NO) synthase and promoting NO release. The 70% decrease in HDL cholesterol that was observed in the WFF group was prevented by almond supplementation; serum and LDL cholesterol were also normalized. CONCLUSIONS: The inhibition of de novo cholesterol synthesis, prevention of hepatic damage, and restoration of vascular function via the protection of endothelium and influence on the NO pathway are some of the mechanisms underlying the medicinal value of almonds in CVDs.