Article

Improvements in Coronary Heart Disease Risk Indicators by Alternate-Day Fasting Involve Adipose Tissue Modulations

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Abstract

The ability of alternate-day fasting (ADF) to modulate adipocyte parameters in a way that is protective against coronary heart disease (CHD) has yet to be tested. Accordingly, we examined the effects of ADF on adipokine profile, body composition, and CHD risk indicators in obese adults. Sixteen obese subjects (12 women/4 men) participated in a 10-week trial with three consecutive dietary intervention phases: (i) 2-week baseline control phase, (ii) 4-week ADF controlled feeding phase, and (iii) 4-week ADF self-selected feeding phase. After 8 weeks of treatment, body weight and waist circumference were reduced (P < 0.05) by 5.7 ± 0.9 kg, and 4.0 ± 0.9 cm, respectively. Fat mass decreased (P < 0.05) by 5.4 ± 0.8 kg, whereas fat-free mass did not change. Plasma adiponectin was augmented (P < 0.05) by 30% from baseline. Leptin and resistin concentrations were reduced (P < 0.05) by 21 and 23%, respectively, post treatment. Low-density lipoprotein cholesterol (LDL-C) and triacylglycerol concentrations were 25% and 32% lower (P < 0.05), respectively, after 8 weeks of ADF. High-density lipoprotein cholesterol (HDL-C), C-reactive protein, and homocysteine concentrations did not change. Decreases in LDL-C were related to increased adiponectin (r = -0.61, P = 0.01) and reduced waist circumference (r = 0.39, P = 0.04). Lower triacylglycerol concentrations were associated with augmented adiponectin (r = -0.39, P = 0.04) and reduced leptin concentrations (r = 0.45, P = 0.03) post-treatment. These findings suggest that adipose tissue parameters may play an important role in mediating the cardioprotective effects of ADF in obese humans.

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... 18-22 0 9 Improvements in coronary heart disease risk indicators by alternate-day fasting involving adipose tissue modulations [53]. ...
... In another study by Bhutani et al. [53], individuals with obesity, enrolled in an alternate-day fasting controlled feeding regimen versus alternate-day fasting self-selected feeding, showed a reduction of 21% and 23% in leptin and resistin levels, respectively. Lower triacylglycerol levels were associated with increased adiponectin and reduced leptin levels. ...
... Specifically, leptin levels are more responsive to a negative energy balance regime, meaning that leptin secretion is more likely to decrease under hypocaloric diet conditions than to increase under hypercaloric diet conditions. Moreover, the levels of leptin appear to rapidly return to the standard starting point once eucaloric conditions are restored [53,59,61,[70][71][72]75]. ...
Article
Obesity and being overweight have been described as potential causes of neurological disorders. Leptin, a peptide expressed in fat tissue, importantly participates in energy homeostasis and storage and has recently been identified for its signaling receptors in neuronal circuits of the brain. Aim: To elucidate whether the endogenous modulation of leptin can be a protection against neuropsychiatric disorders. Method: A systematic review was performed in accordance with the PRISMA-P method, and reports of studies containing data on leptin concentrations in healthy individuals with or without obesity were retrieved from the PubMed database, using the combinations of Mesh terms for “Leptin” and “Metabolism”. Results: Forty-seven randomized and non-randomized controlled trials, dating from 2000 to 2021, were included in the qualitative synthesis. Discussion and conclusions: Leptin secretion displays a stabilizing pattern that is more sensitive to a negative energy intake imbalance. Leptin levels influence body weight and fat mass as a pro-homeostasis factor. However, long-term exposure to elevated leptin levels may lead to mental/behavioral disorders related to the feeding and reward systems.
... 18-22 0 9 Improvements in coronary heart disease risk indicators by alternate-day fasting involving adipose tissue modulations [53]. ...
... In another study by Bhutani et al. [53], individuals with obesity, enrolled in an alternate-day fasting controlled feeding regimen versus alternate-day fasting self-selected feeding, showed a reduction of 21% and 23% in leptin and resistin levels, respectively. Lower triacylglycerol levels were associated with increased adiponectin and reduced leptin levels. ...
... Specifically, leptin levels are more responsive to a negative energy balance regime, meaning that leptin secretion is more likely to decrease under hypocaloric diet conditions than to increase under hypercaloric diet conditions. Moreover, the levels of leptin appear to rapidly return to the standard starting point once eucaloric conditions are restored [53,59,61,[70][71][72]75]. ...
Article
Full-text available
Background: Obesity and being overweight have been described as potential causes of neurological disorders. Leptin, a peptide expressed in fat tissue, importantly participates in energy homeostasis and storage and has recently been identified for its signaling receptors in neuronal circuits of the brain. Aim: To elucidate whether the endogenous modulation of leptin can be a protection against neuropsychiatric disorders. Method: A systematic review was performed in accordance with the PRISMA-P method, and reports of studies containing data of leptin concentrations in healthy individuals with or without obesity were retrieved from the PubMed database, using the combinations of Mesh terms for "Leptin" and "Metabolism". Results: Forty-seven randomized and non-randomized controlled trials, dating from 2000 to 2021, were included in the qualitative synthesis. Discussion and conclusions: Leptin secretion displays a stabilizing pattern that is more sensitive to a negative energy intake imbalance. Leptin levels influence body weight and fat mass as a pro-homeostasis factor. However, long-term exposure to elevated leptin levels may lead to mental/behavioral disorders related to the feeding and reward systems.
... Although different IF regimens have been clinically tested, ADF remains to be the most-studied intervention. Many studies consistently show benefits of short-term (8 -12 wk) ADF in obese individuals, including reduction in body weight and fat mass, and decreases in triglycerides and total and LDL cholesterol (8,49,95). However, ADF has had inconsistent effects on HDL cholesterol levels (9, 50). ...
... In humans, there is a general consensus that IF improves cardiovascular health as a result of improvements in plasma lipid and inflammatory marker profile. As mentioned above, several clinical studies have shown that ADF reduces plasma triacylglycerol, total and LDL cholesterol level, with inconsistencies in HDL level change (8,9,13,48,72,92,94). Collectively, findings reveal that improved plasma lipid profile may be reflective of cardioprotective effects of IF in humans. ...
... Furthermore, high BP is a frequent measure and determinant of CVD risk. Eight to twelve weeks of ADF in obese individuals led to reduced systolic BP or reduced systolic and diastolic BP (8,94,95). A long-term study also showed that 5:2 IF for 6 months led to decreases in both systolic and diastolic BP (37). ...
Article
Intermittent fasting (IF) is a widely practiced dietary method that encompasses periodic restriction of food consumption. Due to its protective benefits against metabolic diseases, aging, and cardiovascular and neurodegenerative diseases, IF continues to gain attention as a preventative and therapeutic intervention to counteract these chronic diseases. Although numerous animal studies have reported positive health benefits of IF, its feasibility and efficacy in clinical settings remain controversial. Importantly, since dietary interventions such as IF have systemic effects, thoroughly investigating the tissue-specific changes in animal models is crucial to identify IF's mechanism and evaluate its potential adverse effects in humans. As such, we will review and compare the outcomes and underlying mechanisms of IF in both animal and human studies. Moreover, the limitations of IF and inconsistencies between preclinical and clinical studies will be discussed to provide insight into the gaps between translating research from bench to bedside.
... The majority of data from alternate day fasting studies come from animal or rodent models and have demonstrated reduced cholesterol and triglyceride concentrations [15,16]. It should be noted that most human trials incorporating alternate day fasting utilized diet interventions which involve consumption of ≤20-25% of habitual dietary intake [17][18][19][20][21]. However, as outlined by Patterson & Sears [9], 3 trials involved fasting of 20-28 hours which were associated with reduced leptin, increased adiponectin [14], increased HDL-c, and reduced TAG levels [13]. ...
... While intermittent fasting has produced changes in markers of cardiometabolic health in healthy and obese populations, such as body composition [17,[19][20][21][32][33][34][35], inflammatory markers (leptin, C-reactive protein) [9], cholesterol [17,18,20,21,35,36] and glucose concentrations [14,35,37,38], it is not clear if a caloric deficit is needed to achieve these changes. One recent study reported increased adiponectin, and decreased fat mass in trained men following an isocaloric TRF for a period of 8 weeks [28] however it is not clear if the same findings would be produced in an ad libitum TRF protocol. ...
... There was no treatment x time interaction for carbohydrate intake (P = . 19), and no main effect for treatment (P = .15) or time (P = .86). ...
Article
Time-restricted feeding (TRF) has been shown to improve body composition, blood lipids, and reduce markers of inflammation and oxidative stress. However, most of these studies come from rodent models and small human samples, and it is not clear if the benefits are dependent upon a caloric deficit, or the time restriction nature of TRF. Based off of previous research, we hypothesized that humans following an ad libitum TRF protocol would reduce caloric intake and this caloric deficit would be associated with greater improvements in cardiometabolic health including blood pressure, body composition, blood lipids, and markers of inflammation and antioxidant status compared to an isocaloric TRF protocol. The purpose of this study was to: (1) examine the impact of TRF on markers of cardio-metabolic health and antioxidant status and (2) determine if the adaptations from TRF would differ under ad libitum compared to isocaloric conditions. Twenty-three healthy men were randomized to either an ad libitum or isocaloric 16:8 (fasting: feeding) TRF protocol. A total of 22 men completed the 28-day TRF protocol (mean ± SD; age: 22 ± 2.5 yrs.; height: 178.4 ± 6.9 cm; weight: 90.3 ± 24 kg; BMI: 28.5 ± 8.3 kg/m2). Fasting blood samples were analyzed for glucose, lipids, as well as adiponectin, human growth hormone, insulin, cortisol, C-reactive protein, superoxide dismutase, total nitrate/nitrite, and glutathione. Time-restricted feeding in both groups was associated with significant (P < .05) reductions in body fat, blood pressure, and significant increases in adiponectin and HDL-c. No changes in caloric intake were detected. In summary, the results from this pilot study in metabolically healthy, active young men, suggest that TRF can improve markers of cardiometabolic health.
... Adiponectin is a collagen-like plasma protein whose concentration decreases in the course of atherosclerosis, insulin resistance, diabetes, and coronary disease [41]. The use of the IF diet increases the secretion of adiponectin from adipocytes [42]. There is an inverse correlation between plasma adiponectin levels and body weight. ...
... An important hormone secreted by adipocytes is leptin [42]. It has a pro-atherogenic effect. ...
... After 8 weeks of using the ADF diet, there was a decrease in leptin concentrations, which was associated with a decreased body weight and fat content. The concentration of resistin significantly decreased after using the ADF diet, which probably was associated with a decrease in body weight [42]. ...
Article
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Intermittent fasting is a form of time restricted eating (typically 16 h fasting and 8 h eating), which has gained popularity in recent years and shows promise as a possible new paradigm in the approach to weight loss and the reduction of inflammation, and has many potential long term health benefits. In this review, the authors will incorporate many aspects of fasting, mainly focusing on its effects on the cardiovascular system, involving atherosclerosis progression, benefits for diabetes mellitus type 2, lowering of blood pressure, and exploring other cardiovascular risk factors (such as lipid profile and inflammation).
...  Weight Loss: Fasting helps people lose weight, with most weight loss being fat. Fasters may slim down, lose body fat, and decrease their body mass index [35,100,122,147,[155][156][157][158] . Thus, fasters may see their risk of heart disease drop. ...
... Fasting studies on humans are unclear. Some studies show that LDL and triglycerides fall while HDL stays the same [35,100,122,147,155,157,158] . Meanwhile, other studies show that LDL and triglycerides are rising and HDL is dropping [122,147] . ...
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As human beings, we often ponder upon our existence on this earth and ask ourselves why we are here. We search for answers through various religions like Hinduism, Buddhism, Christianity, Islam, and Judaism. They share a common theme where God wants us to use all our talents and become closer to Him. We examine methods like fasting, meditation, lucid dreaming, sensory deprivation, and mind-altering drugs such as psychedelics and marijuana to explore our minds and awaken our spirituality. We delve into the deep depths of our minds and psyches to gain greater awareness and uncover hidden aspects of ourselves. Through this journey, we discover our true selves and purpose in life while traversing the path to enlightenment.
... Among these studies, 14 reported a reduction in BW compared to the baseline after implementing IF [20][21][22][24][25][26][27][28][29][30][31][32][33][34]. Eight studies indicated a greater weight loss in the IF group compared to the control groups [24,26,27,[35][36][37][38][39], while another eight studies found no significant difference in weight loss between the IF and control groups [19,22,25,28,31,33,34,40]. TRE and ADF consistently showed decreases in BW, BF, and BMI, whereas the outcomes of IER were more uncertain. When no control group was included, and groups were followed over time, TRE demonstrated beneficial effects on reducing BW in both obese and overweight individuals compared to their baseline [20,21,39]. ...
... Eight studies indicated a greater weight loss in the IF group compared to the control groups [24,26,27,[35][36][37][38][39], while another eight studies found no significant difference in weight loss between the IF and control groups [19,22,25,28,31,33,34,40]. TRE and ADF consistently showed decreases in BW, BF, and BMI, whereas the outcomes of IER were more uncertain. When no control group was included, and groups were followed over time, TRE demonstrated beneficial effects on reducing BW in both obese and overweight individuals compared to their baseline [20,21,39]. However, no subgroups based on BMI categories were studied. ...
Article
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Metabolic syndrome (MetS) has become a significant public health concern globally. Weight managementis crucial in controlling MetS risk factors, making energy balance and weight loss strategies important in nutrition recommendations. Intermittent fasting (IF) has gained traction as a dietary approach for weight management and cardiovascular risk reduction. However, the effects of IF on cardiovascular risk factors have been inconsistent in previous studies. This review aims to summarize the effects of various types of IF on body mass index (BMI), glycemia, lipid profile, and blood pressure, while providing insights into their clinical implications. A comprehensive search of interventional studies and meta-analyses was conducted, and the results were analyzed. The findings indicate that different types of IF lead to mixed effects. Time-restricted eating (TRE) and alternate-day fasting (ADF) consistently showed decreases in BMI, while the outcomes of intermittent energy restriction (IER) were more uncertain. The effects of IF on glycemia and lipid profile were also variable, with TRE and ADF generally showing positive results. However, the impact of IER remained inconsistent. More research is needed to understand the long-term effects and optimal implementation of IF for managing metabolic syndrome and cardiovascular risk factors.
... In addition to the results above, 7 Bhutani et al published a secondary analysis which showed that while waist circumference decreased by 4.0 � 0.9 cm, C-reactive protein, an inflammatory biomarker independently associated with cardiovascular risk, 57 did not change as a result of mADF. 58 metabolic kitchen and ate their own food ad libitum on feasting days. ...
... The proposed explanations for the benefits of intermittent fasting ance. 12,[16][17][18]20,22,23,24,55,58,64,70 Likewise, when energy restriction in the intermittent fasting group was equivalent with baseline intake or to comparison/control group, weight loss either did not occur or did not differ from the comparison group. 27,30,31,37,51,62,67,69,73 Lack of reporting or inadequate reporting of energy balance, however, is one of the predominant problems across mADF, cADF and TRE interventions. ...
Article
Continuous energy restriction is currently considered first‐line dietary therapy for weight loss in individuals with obesity. Recently, interventions which alter eating window and time of eating occasions have been explored as means to achieve weight loss and other cardiometabolic improvements such as reduction in blood pressure, glycemia, lipids and inflammation. It is unknown, however, whether these changes result from unintentional energy restriction or from other mechanisms such as alignment of nutrient intake with the internal circadian clock. Even less is known regarding the safety and efficacy of these interventions in individuals with established chronic noncommunicable disease states such as cardiovascular disease. This review examines the effects of interventions which alter both eating window and time of eating occasions on weight and other cardiometabolic risk factors in both healthy participants and those with established cardiovascular disease. We then summarize the state of existing knowledge and explore future directions of study. This article is protected by copyright. All rights reserved.
... Conversely, Varady et al. found that 8-isoprostane decreased after 10 weeks of IF (6); these results were similar to those of a trial by Peterson et al. (23). Haus et al. reported that adiponectin and leptin levels decreased after a course of 24 weeks (29), and these results were confirmed by Varady et al. in a beforeafter study (22). Significant changes in IL-6 and TNF-α levels were observed in a study by Zouhal et al. (26). ...
... Six studies found that fasting insulin, fasting glucose, and HOMA-IR levels were improved after IF than before (6,8,23,24,26,29). Augmentation of lipid metabolism was observed in a study by Varady et al. in obese subjects (22). ...
Article
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Introduction strategy of periodic food restriction and fixed eating windows, could beneficially modify individuals by losing body weight, regulating glucose or lipid metabolism, reducing blood pressure, and modulating the immune system. Specific effects of IF and its mechanisms have not yet been assessed collectively. Thus, this systematic review aims to summarize and compare clinical trials that explored the immunomodulatory effects of IF. Methods After screening, 28 studies were included in this systematic review. Results In addition to weight loss, IF could benefit health subjects by strengthening their circadian rhythms, migrating immune cells, lower inflammatory factors, and enriching microbials. In addition of the anti-inflammatory effect by regulating macrophages, protection against oxidative stress with hormone secretion and oxidative-related gene expression plays a key beneficial role for the influence of IF on obese subjects. Discussion Physiological stress by surgery and pathophysiological disorders by endocrine diseases may be partly eased with IF. Moreover, IF might be used to treat anxiety and cognitive disorders with its cellular, metabolic and circadian mechanisms. Finally, the specific effects of IF and the mechanisms pertaining to immune system in these conditions require additional studies.
... The most popular is alternate day fasting (ADF), which involves "fast days" alternating with "feed days" (ad libitum food consumption), typically carried out for weeks to months (78). During modified ADF (mADF) a small number of calories (e.g., 25% of energy requirements) is allowed on "fast days" (18,(79)(80)(81)(82)(83). There are also 1/6 and 2/5 schedules (called periodic fasting, cyclic fasting, or intermittent calorie restriction) that involve fasting for one or two days a week, respectively (84)(85)(86)(87). ...
... IF regimens beneficially alter several aspects of adipocyte biology, including morphology, lipid metabolism, and adipokine release (22). In particular, various IF regimens have been shown to decrease serum leptin concentration (22,78,80,84) and increase ghrelin (78). Moreover, adiponectin modulates insulin activity, reduces insulin levels, and improves beta cell functions (10). ...
Article
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Obesity is a condition associated with an increased risk of metabolic disorders, and in particular of type-2 diabetes (T2D). The treatment and prevention of obesity and associated metabolic disorders present great medical challenges. A major therapeutic goal in T2D is to control blood glucose levels, which can be achieved by pharmacological and nonpharmacological measures. The latter include increased physical activity and reduction of body fat mass by limiting dietary caloric content. Low-calorie diets (LCDs) involve a reduction in daily caloric intake by 25% to 30%. LCDs should be individualized depending on the patient's energy requirements, the severity of the obesity, and any accompanying diseases and treatments. Intermittent fasting (IF) involves caloric restriction for one or several days a week, or every day as the prolongation of the overnight fast. The results of recent clinical trials have shown that LCDs and intermittent fasting in patients with obesity (including those with coexisting T2D) can lead to a reduction in body fat mass and metabolic parameter improvements. These beneficial effects arise not only from the loss of body mass, but also from the activation of metabolic pathways specific to fasting conditions. However, the paucity of large-scale randomized controlled trials makes it difficult to prescribe LCDs or IF as reliable, routine methods for successful and stable weight loss.
... In contrast, ADF has been observed to mitigate oxidative stress. Interestingly, research suggests that while MDA levels in the liver significantly increase after 4 weeks of ADF treatment, prolonged ADF treatment spanning 8 to 16 weeks reduces MDA levels in visceral tissue of rats experiencing oxidative stress induced by conditions such as diabetes or spontaneous tumors [42,43]. ...
Article
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Purpose: The purpose of this study was to assess the effect of alternate-day fasting (ADF) concerning sex as well as its function in systemic and tissue-level oxidative stress alterations associated with aging. Materials and methods: Forty-two female (n=21) and male (n=21) Wistar rats (aged 16 months) were separated into six groups (n=7 each):Group-1 (control-male), Group-2 (1-month,ADF-male), Group-3 (2-month,ADF-male), Group-4 (control-female), Group-5 (1-month,ADF-female), and Group-6 (2-month,ADF-female). The ADF protocol was applied every other day for 24-h of fasting (three days/week). Serum samples were analyzed via ELISA to measure total oxidant-antioxidant status (TOS-TAS), and the oxidative stress index (OSI) was calculated. Results: 2-months of ADF treatment reduced body weight (BW) compared compliance control groups (P
... Intermittent fasting (IF) is an eating pattern that involves alternating periods of fasting and eating [2,5,15]. For instance, 16:8-intermittent fasting involves fasting for 16 h a day and eating during the remaining 8 h. ...
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Background Research on intermittent fasting has shown that it can improve a variety of health outcomes, including blood sugar control, blood lipid levels and blood pressure. Only few studies document longer periods of fasting, especially in rehabilitation participants. Cardiac inpatient rehabilitation follows a multidisciplinary approach including change of health behaviour to reduce patients’ risk of future cardiovascular events. To date, evidence suggests that intermittent fasting can be an effective way to improve health and well-being, but more research is needed to fully understand its long-term effects and factors that promote the implementation. Therefore, the aim of the ongoing InterVFast trial is to investigate the effectiveness of intermittent fasting amongst cardiac rehabilitation patients after 4-week inpatient rehabilitation as well as 3 and 12 months subsequently including patients’ perspective. Methods This single-centre randomized controlled trial evaluates the effectiveness of the InterVFast intervention in weight loss (primary outcome). We also examine patients’ acceptance and the effect on relevant outcomes as blood glucose and triglyceride levels, cholesterol and high-sensitivity C-reactive protein. Weight, blood samples and clinical data are collected as part of the initial and final examination during inpatient rehabilitation. During inpatient rehabilitation, participants daily note fasting intervals and meals eaten as well as practicability in a fasting diary. In addition, interviews about perceived advantages and disadvantages and acceptance are carried out with the participants in the IG. A standardized follow-up examination (weight, blood samples) will be carried out by the family doctor after 3 and 12 months (t2 and t3). Discussion Compared to other weight-loss intervention studies, our study addresses patients with coronary heart disease and includes patients’ acceptance as well as long-term maintenance. It is hypothesized that participation in the InterVfast intervention will improve relevant health outcomes in a sample of cardiac rehabilitation patients and thus constitute a behavioural prevention strategy to reduce the risk of future cardiac events and improve overall health and quality of life. Trial registration ClinicalTrials.gov DRKS00023983. Registered on February 17, 2022.
... Se observó una reducción significativa del nivel de triglicéridos, leptina y proteína C reactiva y un aumento de adiponectina, mientras que el colesterol HDL (col-HDL), colesterol LDL (col-LDL), resistina y homocisteína no presentaron cambios significativos 18 . En otro estudio 22 se sometió a un grupo de adultos con obesidad (n = 16, 12 mujeres) a una intervención dietaria de 10 semanas dividida en 3 fases: (i) fase inicial de control (2 semanas); (ii) fase de alimentación controlada con ADA (4 semanas); y (iii) fase de alimentación autoseleccionada con ADA (4 semanas) 22 . Respecto al perfil lipídico, el col-LDL se redujo significativamente mientras que las concentraciones de col-HDL y triglicéridos no se modificaron 23 . ...
Article
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Intermittent fasting (IF) has gained increasing scientific and general attention. Most studied forms of IF include alternate-day fasting, modified alternate-day fasting, and time-restricted eating (TRE). Several cardiometabolic effects of IF have been described in animal models and, to a lesser extent, in humans. This review analyzes the impact of IF on weight loss, glucose metabolism, blood pressure, and lipid profile in humans. A literature search was conducted in the Pubmed/Medline, Scopus, and Google Scholar databases. Controlled observational or interventional studies in humans, published between January 2000 and June 2021, were included. Studies comparing IF versus religious fasting were not included. Most studies indicate that the different types of IF have significant benefits on body composition, inducing weight loss and reducing fat mass. Changes in cardiometabolic parameters show more divergent results. In general, a decrease in fasting glucose and insulin levels is observed, together with an improved lipid profile associated with cardiovascular risk. High heterogeneity in study designs was observed, particularly in studies with TRE, small sample sizes, and short-term interventions. Current evidence shows that IF confers a range of cardiometabolic benefits in humans. Weight loss, improvement of glucose homeostasis and lipid profile, are observed in the three types of IF protocols evaluated.
... The feeding window can be shortened to 4 h in a more rigorous approach, the so-called 20:4 method [17]. Another protocol is ADF, consisting of a 24 h fasting period alternating with a 24 h eating period, repeated two or three times a week [18,19]. Also widely used is twice-per-week fasting (TWF) (e.g., the so-called 5:2 diet), which involves a very low-calorie diet two days a week (consecutive or non-consecutive), following ad libitum feeding for the other five days [16]. ...
Article
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Over the last decade, studies suggested that dietary behavior modification, including fasting, can improve metabolic and cardiovascular markers as well as body composition. Given the increasing prevalence of people with type 1 (T1DM) and type 2 diabetes mellitus (T2DM) and the increasing obesity (also in combination with diabetes), nutritional therapies are gaining importance, besides pharmaceutical interventions. Fasting has demonstrated beneficial effects for both healthy individuals and those with metabolic diseases, leading to increased research interest in its impact on glycemia and associated short- and long-term complications. Therefore, this review aimed to investigate whether fasting can be used safely and effectively in addition to medications to support the therapy in T1DM and T2DM. A literature search on fasting and its interaction with diabetes was conducted via PubMed in September 2022. Fasting has the potential to minimize the risk of hypoglycemia in T1DM, lower glycaemic variability, and improve fat metabolism in T1DM and T2DM. It also increases insulin sensitivity, reduces endogenous glucose production in diabetes, lowers body weight, and improves body composition. To conclude, fasting is efficient for therapy management for both people with T1DM and T2DM and can be safely performed, when necessary, with the support of health care professionals.
... Interestingly, activated BAT and increased browning of WAT in Apoe -/mice exacerbate atherosclerosis [49,50], and genetic deletion of Ucp1 in Apoe -/mice has been reported to prevent atherosclerotic plaque growth [49,50]. Furthermore, in humans, improvements in coronary heart disease risk factors by every-other-day fasting involved modulation of adipose tissue parameters [20]. ...
Article
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In humans and animal models, intermittent fasting (IF) interventions promote body weight loss, improve metabolic health, and are thought to lower cardiovascular disease risk. However, there is a paucity of reports on the relevance of such nutritional interventions in the context of dyslipidemia and atherosclerotic cardiovascular diseases. The present study assessed the metabolic and atheroprotective effects of intermittent fasting intervention (IF) in atherosclerosis-prone apolipoprotein E-deficient (Apoe-/-) mice. Groups of male and female Apoe-/- mice were fed a regular (chow) or atherogenic (high-fat, high-cholesterol, HFCD) diet for 4 months, either ad libitum or in an alternate-day fasting manner. The results show that IF intervention improved glucose and lipid metabolism independently of sex. However, IF only decreased body weight gain in males fed chow diet and differentially modulated adipose tissue parameters and liver steatosis in a diet composition-dependent manner. Finally, IF prevented spontaneous aortic atherosclerotic lesion formation in mice fed chow diet, irrespective of sex, but failed to reduce HFCD-diet-induced atherosclerosis. Overall, the current work indicates that IF interventions can efficiently improve glucose homeostasis and treat atherogenic dyslipidemia, but a degree of caution is warranted with regard to the individual sex and the composition of the dietary regimen.
... Interestingly, activated BAT and increased browning of WAT in Apoe -/-mice exacerbate atherosclerosis [50,51], and genetic deletion of Ucp1 in Apoe -/-mice has been reported to prevent atherosclerotic plaque growth [50,51]. Furthermore, in humans, improvements in coronary heart disease risk factors by every-other-day fasting involved modulation of adipose tissue parameters [20]. ...
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In humans and animal models, intermittent fasting (IF) interventions promote body weight loss, improve metabolic health, and are thought to lower cardiovascular disease risk. However, there is a paucity of reports on the relevancy of such nutritional interventions in the context of dyslipidemia and atherosclerotic cardiovascular diseases. The present study assessed the metabolic and atheroprotective effects of intermittent fasting intervention (IF) in atherosclerosis-prone apolipoprotein E-deficient (Apoe-/-) mice. Groups of male and female Apoe-/- mice were fed a regular (chow) or atherogenic (high-fat, high-cholesterol, HFCD) diet for 4 months, either ad libitum or in an alternate-day fasting manner. The results show that IF intervention improved glucose and lipid metabolism independently of sex. However, IF only decreased body weight gain in males fed chow diet and differentially modulated adipose tissue parameters and liver steatosis in a diet composition-dependent manner. Finally, IF prevented spontaneous aortic atherosclerotic lesions formation in mice fed chow diet, irrespective of sex but failed to reduce HFCD-diet-induced atherosclerosis. Overall, the current work indicates that IF interventions can efficiently improve glucose homeostasis and treat atherogenic dyslipidemia, but a degree of caution is warranted with regard to the individual sex and the composition of the dietary regimen.
... Intermittent fasting (IF) interventions have been found to provide multiple health benefits, including combating obesity [1], insulin resistance [2], dyslipidemia [3], hypertension [4], as well as extending healthy lifespan in pre-clinical models [5]. Time-restricted eating (TRE) is a popular form of IF that restricts all calorie intake, without altering diet quantity and quality, to a 6-10 h period. ...
Article
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Time-restricted eating (TRE), a popular form of intermittent fasting, has been demonstrated to provide multiple health benefits, including an extension of healthy lifespan in preclinical models. While the specific mechanisms remain elusive, emerging research indicates that one plausible mechanism through which TRE may confer health benefits is by influencing the expression of the epigenetic modulator circulatory miRNAs, which serve as intercellular communicators and are dysregulated in metabolic disorders, such as obesity. Therefore, the goal of this pilot study is to examine the effects of a 4-week TRE regimen on global circulatory miRNA from older (≥65 years) overweight participants. Pre- and post-TRE regimen serum samples from nine individuals who participated in the Time to Eat clinical trial (NCT03590847) and had a significant weight loss (2.6 kg, p < 0.01) were analyzed. The expressions of 2083 human miRNAs were quantified using HTG molecular whole transcriptome miRNA assay. In silico analyses were performed to determine the target genes and biological pathways associated with differentially expressed miRNAs to predict the metabolic effects of the TRE regimen. Fourteen miRNAs were differentially expressed pre- and post-TRE regimen. Specifically, downregulated miRNA targets suggested increased expression of transcripts, including PTEN, TSC1, and ULK1, and were related to cell growth and survival. Furthermore, the targets of downregulated miRNAs were associated with Ras signaling (cell growth and proliferation), mTOR signaling (cell growth and protein synthesis), insulin signaling (glucose uptake), and autophagy (cellular homeostasis and survival). In conclusion, the TRE regimen downregulated miRNA, which, in turn, could inhibit the pathways of cell growth and activate the pathways of cell survival and might promote healthy aging. Future mechanistic studies are required to understand the functional role of the miRNAs reported in this study.
... IF diet regimens were found to reduce the risk of obesity both in animal [57] and human studies [58]. IF was found to improve indicators of coronary heart disease in obese men and women, such as reducing body weight, waist circumference, and body fat mass [59]. Previous reports have recorded a cardioprotective impact of IF diet and attributed such effect to the reduction in fat tissue, especially visceral fat tissue [60,61]. ...
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Background Aging is associated with cardiovascular and metabolic changes, increasing the susceptibility to acute myocardial infarction (AMI). Intermittent fasting (IF) has a beneficial effect on the age-associated cardiovascular diseases. The present study was planned to investigate the possible protective effect of IF against acute AMI induced by isoproterenol (ISO) in old rats and its possible underlying mechanisms mediated by heart and pancreatic autophagy. Thirty Male Wistar rats were divided into four groups: adult; old; Old-ISO (rats subjected to AMI by ISO) and Old-F-ISO groups (rats were subjected to IF for 4 weeks and AMI by ISO). Results IF significantly increased the mRNA expression of cardiac Atg-5 and pancreatic Atg-7 in Old-F-ISO versus old and adult groups. This was associated with a significant decrease in serum troponin-I, serum creatine kinase (CK-MB), cardiac malondialdehyde and cardiac TNF-α, fasting plasma glucose, and HOMA-IR in Old-F-ISO compared to Old-ISO group. Also, IF significantly decreased the age-related overall and visceral obesity in Old-F-ISO versus old and Old-ISO groups. Histological studies revealed attenuation of the local inflammatory response in Old-F-ISO versus Old-ISO group. Pancreatic Atg-7 and heart Atg-5 were significantly increased in Old-ISO versus old rats. Conclusions IF protects against acute AMI in old rats, possibly, via chronic activation of heart Atg-5 and pancreatic Atg-7, and alleviation of age-related overall and visceral obesity. Thus, IF could be a dietary lifestyle modification for attenuation of the susceptibility to acute AMI in aged population. On the other hand, acute activation of heart and pancreatic autophagy by ISO might augment cardiac injury.
... Various studies, in which carbohydrate restriction and intermittent fasting were part of the intervention, not only showed a significant reduction in body weight in participants who were overweight but also a concomitant decrease in the concentration of inflammatory markers in the blood [30][31][32]. Missing insulin signalling during fasting can therefore be seen as a regulator of the immune system as it influences the release of inflammatory cytokines, such as IL-6, in the body [33][34][35]. Moreover, intermittent fasting can delay immune senescence, which is characterised by a progressive decline in immune function with increasing age, according to a publication in which the number of hematopoietic stem cells increased fivefold through a fast-imitating diet [36]. ...
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Lifestyle interventions, including meal replacement, are effective in the prevention and treatment of type-2-diabetes and obesity. Since insulin is the key weight regulator, we hypothesised that the addition of meal replacement to a lifestyle intervention reduces insulin levels more effectively than lifestyle intervention alone. In the international multicentre randomised controlled ACOORH (Almased Concept against Overweight and Obesity and Related Health Risk) trial, overweight or obese persons who meet the criteria for metabolic syndrome (n = 463) were randomised into two groups. Both groups received nutritional advice focusing on carbohydrate restriction and the use of telemonitoring devices. The intervention group substituted all three main meals per day in week 1, two meals per day in weeks 2–4, and one meal per day in weeks 5–26 with a protein-rich, low-glycaemic meal replacement. Data were collected at baseline and after 1, 3, 6 and 12 months. All datasets providing insulin data (n = 446) were included in this predefined subanalysis. Significantly higher reductions in insulin (−3.3 ± 8.7 µU/mL vs. −1.6 ± 9.8 µU/mL), weight (−6.1 ± 5.2 kg vs. −3.2 ± 4.6 kg), and inflammation markers were observed in the intervention group. Insulin reduction correlated with weight reduction and the highest amount of weight loss (−7.6 ± 4.9 kg) was observed in those participants with an insulin decrease > 2 µU/mL. These results underline the potential for meal replacement-based lifestyle interventions in diabetes prevention, and measurement of insulin levels may serve as an indicator for adherence to carbohydrate restriction.
... The objective of IMF is to create a net reduction in energy intake that causes it to fall below energy expenditure, thereby creating a state of negative energy balance and inducing weight loss (Hill, Wyatt & Peters, 2012). Work by various groups has consistently shown that such an approach is associated with significant reductions in body mass in obese participants, whilst also improving blood lipid profile and lowering concentrations of inflammatory markers (Johnson, Summer, Cutler, Martin, Hyun & Dixit, 2007;Varady, Bhutani, Church & Klempel, 2009;Bhutani, Klempel, Berger & Varady, 2010). Although these findings are broadly comparable to those seen following a period of daily calorie restriction (Larson- Barnosky, Klempel, Bhutani & Hoddy, 2017), current understanding of how IMF affects human health and metabolism is far from complete. ...
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Many studies have been conducted on intermittent fasting. However, their results were varied and highly inconsistent. Most of the studies reported a reduction in body weight. Other studies found that body weight increased or was maintained during this period. Weight loss continues to be a growing concern for many people in industrialized countries. Key components in weight loss are increased in daily physical activity level and diet modifications including appetite control. Though consumers have become more concerned with “healthy” and “fresh” foods, most highly available and affordable foods tend to be those that are high in calories. Easy access to high calorie foods, combined with multi-media advertisements make appetite control one of the harder obstacles to overcome when trying to lose weight. Hence, this study will investigate the impact of intermittent fasting on brain and weight loss. This study may also show if the level of physical activity is a major contributing factor to the values in each of these areas during the fasting. This study employed the qualitative approach which avails significant research benefits to the area of study. The study incorporated elements of science and deductions from reports and texts analyzed are qualitative in nature. In qualitative approach, relevant search criteria sourced information from secondary sources – journals, books and literature reviewed from previous research in the area of study. Several studies reviewed in this paper showed that intermittent fasting may induce decrease in the weight of body and some organs, and fasting regularly will improve brain health and lessen the risk of cognitive decline and brain disorders. Keywords: Intermittent fasting, impact, weight loss, brain health, qualitative approach, appetite control, calorie foods, diet modifications, physical activities
... Intermittent fasting (IF), in which energy consumption is repeatedly and intentionally interrupted or markedly reduced for a period of time, has been a focus of recent research and proposed as a weight-loss strategy with additional cardiometabolic benefits in individuals with overweight and obesity. These additional benefits include reduction in total cholesterol and blood pressure, and improved insulin sensitivity (7)(8)(9)(10)(11)(12). Although IF interventions have not been standardized, common regimens include time-restricted feeding (TRF), in which feeding is allowed for only a window of 4 to 8 hours per day with 16 to 20 hours of fasting (13)(14)(15)(16), and intermittent or short-term energy restriction through very-low calorie diets (VLCDs), in which caloric consumption remains between 300 and 600 kcal/day (17). ...
Article
Context Intermittent fasting (IF) has been proposed as a weight-loss strategy with additional cardio-metabolic benefits in individuals with obesity. Despite its growing popularity, the effect of IF in patients with type 2 diabetes (T2DM) remains unclear. Objective We conducted a systematic review and meta-analysis to evaluate the metabolic impact of IF as compared to standard diet in patients with T2DM. Data sources Embase, PubMed, and clinicaltrials.gov between 1950 and August-12-2020. Study selection Randomized, diet-controlled studies evaluating any IF intervention in adults with T2DM. Data extraction We examined the impact of IF on weight loss and glucose-lowering by calculating pooled estimates of the absolute differences in bodyweight and glycated hemoglobin (HbA1c) as compared to control group using random-effects model. Data Synthesis Seven studies (n=338 participants; mean BMI 35.65kg/m 2, mean baseline HbA1c of 8.8%) met our inclusion criteria. IF induced greater decrease in bodyweight by -1.89kg (95%CI -2.91 to -0.86 kg) as compared to regular diet, with no significant between-study heterogeneity (I 221.0%, P=0.28). The additional weight loss induced by IF was greater in studies with heavier population (BMI >36kg/m 2) [-3.24kg (95%CI -5.72 to -1.15 kg)] and in studies of shorter duration (≤ 4 months) [-3.73kg (95%CI -7.11 to -0.36kg)]. IF was not associated with further reduction in HbA1c as compared to standard diet [HbA1c -0.11% (95%CI -0.38 to 0.17%)]. Conclusions Current evidence suggests that IF is associated with greater weight loss in patients with T2DM as compared with standard diet, with similar impact on glycemic control.
... Studies in human subjects have demonstrated an improvement in health indicators both in healthy and diseased conditions. These health outcomes are not limited to solely weight control but in a plethora of other circumstances including cardiovascular disorders, metabolic syndrome, and cancer [2,[5][6][7][8][9][10][11][12]. ...
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We examined the evidence for intermittent fasting (IF) as a preventative tool to influence β-amyloid in animal models of Alzheimer’s disease (AD). A Scopus, Ovid, PubMed, and Web of Science (WoS), search yielded 29 results using the keywords “amyloid beta”, “intermittent fasting”, “intermittent caloric restriction”, “alternate day fasting”, “modified alternate-day fasting”, “time-restricted feeding”, “Ramadan fast”, “intermittent calori* restriction”, “intermittent restrictive diet”, and “Alzheimer*”. Five research articles addressed directly the effects of intermittent fasting on β-amyloid levels in animal models of AD: alternate day fasting (ADF) and time-restricted feeding (TRF) methods were incorporated in these studies. The study designs were found to be heterogeneous. Variations in the levels of β-amyloid peptides or plaque in either the hippocampus, cortical areas, or both in animals following dietary intervention were observed as compared to the ad libitum group. Non-significant changes were observed in three studies, while two studies interestingly demonstrated amelioration and reduction in β-amyloid levels. Given the conflicting results obtained from this study, significant care has to be taken into consideration before the protocol can be applied as a preventative approach to treat Alzheimer’s disease. Longitudinal research is warranted to fully grasp how dietary habits can help alleviate the disease either through upstream or downstream of AD pathology.
... Diversas são as evidências que mostram os efeitos benéficos do jejum intermitente em indivíduos obesos e com comorbidades a ela associadas como hipertensão arterial, diabetes mellitus e aterosclerose, sugerindo assim o jejum intermitente enquanto terapia não medicamentosa na prevenção e tratamento dessas condições. Tais desfechos promovidos por esta estratégia dietética estão intimamente associados com um aumento na eficiência metabólica, incluindo além da maior utilização de triglicerídeos do tecido adiposo conforme acima descrito, a redução de fatores pró inflamatórios e a maior capacidade de resistência a fatores estressores (Longo & Mattson, 2014;Mattson & Wan, 2005;Golbidi et al., 2017;Carter et al., 2016;Hoddy et al., 2014;Hoddy et al., 2016;Varady et al., 2013;Bhutani et al., 2010;Wegman et al., 2015). ...
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O jejum intermitente é uma estratégia dietética, caracterizada por modificações alimentares que envolvem períodos regulares de ingesta calórica intercaladas com abstenção dietética com duração superior a um jejum típico durante o sono noturno. A literatura mostra que a combinação do jejum com a realização de exercícios físicos é capaz conferir alterações metabólicas e redução da adiposidade corporal, contudo, pode causar efeitos negativos no desempenho físico. O objetivo do presente trabalho é apresentar resultados de pesquisas atuais que avaliaram o impacto das referidas intervenções sobre parâmetros de composição corporal e de desempenho físico. Para tal, foi realizado um levantamento bibliográfico na base de dados Pubmed. Após análise dos 4 artigos selecionados, constatou-se que a combinação crônica do jejum intermitente com exercícios físicos promove melhorias na composição corporal e não compromete o ganho ou a manutenção do desempenho físico. Entretanto, intervenções mais curtas, com modelos de jejum que promovam déficit calórico sem uma adequada ingestão de proteína parece afetar negativamente o desempenho físico e mitigar o ganho de massa magra.
... Previous studies have also reported results in accordance with our findings; for example, Varady et al., [23] showed that 4-weeks adherence to ADF can decrease visceral fat and redistribute fat to subcutaneous compartments. Bhutani et al., [32] reported a favorable effect of 8-weeks ADF on obesity treatment, where body weight, waist circumference and fat mass was markedly decreased. Moreover, Varady et al. [33] also showed that following an ADF diet resulted in a reduction of 3.6 ± 0.7 kg of fat mass among normal and overweight subjects after 8 weeks. ...
Article
Background and Objective: The aim of present study was to compare, and determine, the effects of a modified alternate-day fasting diet vs. calorie restriction on inflammatory indices and coagulation factors. Methods: This was a randomized clinical trial consisting of 80 metabolic syndrome patients, who were enrolled and randomly dichotomized into a modified alternate-day fasting diet or calorie restriction group for 4 months. We measured weight, body mass index (BMI), waist circumstance (WC), waist-hip-ratio (WHR) and fat mass as primary outcomes and assessed high sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and coagulation factors levels as secondary outcomes before and after intervention. Results: Compared to the calorie restriction diet, following a modified alternate-day fasting diet led to a greater reduction in body weight (kg) (-6.43 ± 4.34 vs -4.11 ± 4.27; P = 0.02), BMI (kg/m2) (-3.19 ± 2.90 vs -1.43 ± 2.72; P = 0.01), fat mass (kg) (-4.88 ± 2.09 vs -3.72 ± 2.43; P = 0.03), WC (cm) (-5.57 ± 5.64 vs -2.32 ± 5.95; P = 0.01) and WHR (-0.05 ± 0.06 vs -0.02 ± 0.07; P = 0.04). Furthermore, a greater change was found in hs-CRP levels (mg/L) (-2.06 ± 1.18 vs -0.97 ± 0.82; P = 0.03), prothrombin time (s) (1.41 ± 2.34 vs -0.41 ± 2.17; P < 0.001), activated partial thromboplastin time (s) (0.26 ± 3.70 vs -1.78 ± 3.56; P = 0.04) in modified alternate-day fasting diet when compared to calorie restriction diet. However, there was no difference in TNF-α or IL-6 and fibrinogen between groups (P > 0.05). Conclusions: These findings suggest that a modified alternate-day fasting diet can be a beneficial alternative for the management of body weight, fat mass and WC as well as hs-CRP and coagulation factors levels among metabolic syndrome patients.
... Intermittent fasting reduces the risk of coronary heart diseases. It improves pointers of coronary heart disease in obese men and women including reduction in body weight, waist circumference, fat mass, low-density lipoprotein cholesterol (LDL-C) and triacylglycerol [13]. IF with high-protein and low calorie diet reduces body weight, BMI, blood lipids and enhances arterial compliance in obese men and women [14]. ...
... There are also strong positive correlations between plasma resistin levels and increases in body mass index (BMI) and visceral fat (18 -20). Conversely, in overweight and obese humans, serum resistin levels have been found to consistently decrease with weight loss attributed to controlled exercise or hypocaloric diets (21)(22)(23). Finally, the importance of resistin as an ASCVD risk factor in obesity is highlighted by the fact that serum resistin levels in humans are predictive of coronary atherosclerosis, independent of the presence of obesity (24). ...
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In this study, our goal was to determine if human resistin plays a role in regulating the uptake of atherogenic low-density lipoproteins in human hepatocytes. Serum levels of resistin, an adipose tissue-derived adipokine, are increased in human obesity and are positively correlated with atherosclerotic cardiovascular diseases. However, the function of resistin in humans is enigmatic. Human hepatocytes (HepG2 and primary) were treated (24 h) with the following: 1) purified human resistin at various concentrations, with and without lovastatin; and 2) obese human serum with elevated resistin levels or serum from which resistin was removed via antibody-immunoprecipitation. The effect of the treatments on cellular low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) messenger ribonucleic acid and protein levels were determined by using real-time polymerase chain reaction and Western blotting, respectively. Resistin, at physiological levels observed in human obesity, down-regulated hepatocyte LDLR expression substantially (by 40%). A key mechanism by which human resistin inhibited LDLR levels was by increased cellular expression of the recently identified protease, PCSK9, which enhances intracellular LDLR lysosomal degradation. The quantitatively important role of human resistin in LDLR expression was demonstrated by antibody-immunoprecipitation removal of resistin in human serum, which decreased serum stimulation of hepatocyte LDLRs markedly (by 80%). Furthermore, resistin diminished statin-mediated up-regulation of the LDLR by 60%, implicating resistin in the relative ineffectiveness of statins in selective target populations. These results reveal for the first time that resistin is a highly attractive therapeutic target in ameliorating elevated serum low-density lipoprotein and, thereby, atherosclerotic cardiovascular diseases in obese humans.
... This led to body mass losses of 5·6 kg, 5·4 kg of which was accounted for by decreases in fat mass (32) . Total cholesterol, LDL-cholesterol and TAG were also reduced by at least 20 %, effects which were associated with improvements in adipokine profile (63) . Subsequent work by the same group neatly demonstrates that these outcomes are similar when applied to cohorts of adults who are overweight (64) , when meal timing on the fasting day is varied (65) , and that concurrent macronutrient manipulation does not exert additive effects (66) . ...
Article
Obesity remains a major public health concern and intermittent fasting is a popular strategy for weight loss, which may present independent health benefits. However, the number of diet books advising how fasting can be incorporated into our daily lives is several orders of magnitude greater than the number of trials examining whether fasting should be encouraged at all. This review will consider the state of current understanding regarding various forms of intermittent fasting (e.g. 5:2, time-restricted feeding and alternate-day fasting). The efficacy of these temporally defined approaches appears broadly equivalent to that of standard daily energy restriction, although many of these models of intermittent fasting do not involve fed-fasted cycles every other 24 h sleep–wake cycle and/or permit some limited energy intake outside of prescribed feeding times. Accordingly, the intervention period therefore may not regularly alternate, may not span all or even most of any given day, and may not even involve absolute fasting. This is important because potentially advantageous physiological mechanisms may only be initiated if a post-absorptive state is sustained by uninterrupted fasting for a more prolonged duration than applied in many trials. Indeed, promising effects on fat mass and insulin sensitivity have been reported when fasting duration is routinely extended beyond sixteen consecutive hours. Further progress will require such models to be tested with appropriate controls to isolate whether any possible health effects of intermittent fasting are primarily attributable to regularly protracted post-absorptive periods, or simply to the net negative energy balance indirectly elicited by any form of dietary restriction.
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Intermittent fasting (IF), characterized by alternating periods of fasting and unrestricted eating, typically within an 8-hour window or less each day has gained significant attention as a possible dietary approach. While it is recognized for its metabolic advantages like weight loss and enhanced glucose and insulin sensitivity, its effect on cardiovascular health remains a topic of mixed opinions. Recent findings suggest a potential downside, with reports indicating a concerning association: a 91% higher risk of cardiovascular disease (CVD) mortality compared to eating spread across a 12- to 16-hour period. Despite this alarming statistic, the evidence is not robust enough to establish a causal link. The impact of IF on CVD is still insufficiently understood, with benefits sometimes exaggerated and risks downplayed in popular discourse. This scoping review aims to synthesize the existing evidence, addressing unresolved questions regarding the benefits and risks of IF, particularly its association with CVD risks and mortality. The goal is to provide a balanced perspective on the potential health implications of IF, emphasizing the need for further research to clarify its long-term effects on cardiovascular health.
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Intermittent fasting (IF) has proven to be a feasible dietary intervention for the wider population. The recent increase in IF clinical trials highlights its potential effects on health, including changes in body composition, cardiometabolic status, and aging. Although IF may have clinical applications in different populations, studies suggest there may be sex-specific responses in parameters such as body composition or glucose and lipid metabolism. Here, the existing literature on IF clinical trials is summarized, the application of IF in both disease prevention and management is discussed, and potential disparities in response to this type of diet between men and women are assessed. Moreover, the potential mechanisms that may be contributing to the sexually dimorphic response, such as age, body composition, tissue distribution, or sex hormones are investigated. This review underscores the need to further study these sex-specific responses to IF to define the most effective time frames and length of fasting periods for men and women. Tailoring IF to specific populations with a personalized approach may help achieve its full potential as a lifestyle intervention with clinical benefits.
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One of the most frequent contributors to co-morbidities or death among individuals living with HIV (PLWH) in antiretroviral therapy (ART) is cardiovascular disease (CVD). Vascular cardiovascular disease, arterial disease, stroke, illness, or cardiac cardiac were among the CVDs that over 50% of PLWH are expected to have a greater likelihood of acquiring. The pathological process on such organism varies by shared vulnerabilities, HIV Viral infection itself, or complications of immunosuppressive medication. With this goal, potential non-pharmacological treatments, including dietary practices like intermittent fasting (IF), are now being investigated globally. The academic community is becoming increasingly interested within IF, a common procedure, because of its prospective advantages for improving blood pressure (BP), chronic inflammation, platelet-derived expansion factor AB, blood lipids as well as lipoproteins and blood vessel intima-media dimension, as well as additional cardiovascular health indicators. Because intermittent fasting has inherent features that improve the main heart disease risk variables as well as modulate inflammation responses linked to arterial disorder, lipid per oxidation, as well as ageing, this review can concentrate with investigating the possible advantages of irregular not eating as an alternatives to medication inexpensive approach to reducing the prevalence of heart conditions within HIV individuals on ART. Through the battle towards the rising incidence of cardiovascular diseases through PLWH, short-term fasting regimes require must be further evaluated in research studies as a significant, innovative, as well as affordable coadjutant of ART.
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The present study was aimed to investigate the effect of intermittent fasting and caloric restricted diet (RD) for 8 weeks on diabetic rats. Forty-nine adult male albino rats were divided into two main groups; the first main group was fed only on basal diet and served as negative control group and the second main group: diabetic rats were induced by a single intra-peritoneal injection of freshly prepared STZ (60 mg/kg BW) then divided into 6 subgroups: Subgroup (1) was fed only on basal diet and was served as positive cont. Subgroup (2) was fed on RD only. Subgroups (3, 4) were fed on basal diet and were deprived of food except water from 5 p.m. to 8 a.m. twice a week and every other day, respectively. Subgroups (5, 6): were fed on RD and intermittent fasting twice a week and every other day, respectively. The results indicated that RD and intermittent fasting significantly decreased the final body weight, feed intake and body weight gain % values as compared to the positive control rats. Diabetic treated rats had significant increase (p<0.05) in insulin concentration and lower glucose levels as well as an improvement in liver functions and lipid profile as compared to the positive control group. Conclusion: the findings suggest that intermittent fasting and caloric restricted diet could have a potential role in managing diabetes.
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Fasting has gained significant attention in recent years for its potential health benefits in various body systems. This review aims to comprehensively examine the effects of fasting on human health, specifically focusing on its impact on different body's physiological systems. The cardiovascular system plays a vital role in maintaining overall health, and fasting has shown promising effects in improving cardiovascular health markers such as blood pressure, cholesterol levels, and triglyceride levels. Additionally, fasting has been suggested to enhance insulin sensitivity, promote weight loss, and improve metabolic health, thus offering potential benefits to individuals with diabetes and metabolic disorders. Furthermore, fasting can boost immune function, reduce inflammation, enhance autophagy, and support the body's defense against infections, cancer, and autoimmune diseases. Fasting has also demonstrated a positive effect on the brain and nervous system. It has been associated with neuroprotective properties, improving cognitive function, and reducing the risk of neurodegenerative diseases, besides the ability of increasing the lifespan. Hence, understanding the potential advantages of fasting can provide valuable insights for individuals and healthcare professionals alike in promoting health and wellbeing. The data presented here may have significant implications for the development of therapeutic approaches and interventions using fasting as a potential preventive and therapeutic strategy.
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Adipose tissue is now recognized as an endocrine organ that secretes bioactive molecules called adipokines. These biomolecules regulate key physiological functions, including insulin sensitivity, energy metabolism, appetite regulation, endothelial function and immunity. Dysregulated secretion of adipokines is intimately associated with obesity, and translates into increased risk of obesity-related cardiovasculo-metabolic diseases. In particular, emerging evidence suggests that adipokine imbalance contributes to the pathogenesis of atherosclerosis. One of the promising diet regimens that is beneficial in the fight against obesity and cardiometabolic disorders is intermittent fasting (IF). Indeed, IF robustly suppresses inflammation, meditates weight loss and mitigates many aspects of the cardiometabolic syndrome. In this paper, we review the main adipokines and their role in atherosclerosis, which remains a major contributor to cardiovascular-associated morbidity and mortality. We further discuss how IF can be employed as an effective management modality for obesity-associated atherosclerosis. By exploring a plethora of the beneficial effects of IF, particularly on inflammatory markers, we present IF as a possible intervention to help prevent atherosclerosis.
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Context: Intermittent fasting, a new-age dietary concept derived from an age-old tradition, involves repetitive cycles of fasting/calorie restriction and eating. Objective: We aim to take a deep dive into the biological responses to intermittent fasting, delineate the disease-modifying and cognitive effects of intermittent fasting, and also shed light on the possible side effects. Methods: Numerous in vitro and in vivo studies were reviewed, followed by an in-depth analysis, and compilation of their implications in health and disease. Results: Intermittent fasting improves the body's stress tolerance, which is further amplified with exercise. It impacts various pathological conditions like cancer, obesity, diabetes, cardiovascular disease, and neurodegenerative diseases. Conclusion: During dietary restriction, the human body experiences a metabolic switch due to the depletion of liver glycogen, which promotes a shift towards utilising fatty acids and ketones in the system, thereby significantly impacting adiposity, ageing and the immune response to various diseases.
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Background: Type 2 diabetes mellitus (T2DM) is a severe public health issue notably impacting human life and health expenditure. It has been observed in literature that intermittent fasting (IF) addresses diabetes and its underlying cause, which benefits people with diabetes. Therefore, this study aimed to evaluate the effectiveness of IF treatment on glycaemic control in people with T2DM compared with control group. Methods: Systematic review and meta-analysis of interventional studies among patients with T2DM with glycated haemoglobin (HbA1c) as an outcome was performed. A comprehensive search of electronic databases, including PubMed, Embase and Google Scholar, for articles published before 24 April 2022, was done. Studies reporting 24 hours of complete fasting or intermittent restricted energy intake (feeding permitted for only 4-8 hours daily, with 16-20 hours of fasting) and reporting changes in HbA1c and fasting glucose levels were eligible. Meta-analysis was performed using Cochrane's Q statistic and the I 2 statistical approach. Results: Eleven studies (13 arms) measuring the effect of IF on patients' HbA1c level were analysed. There was no statistically significant difference between IF and control groups (Standardized mean difference [SMD]-0.08, 95% confidence interval [CI]-0.20 to 0.04;p=0.19, I 2 =22%). Overall, seven studies on patients' fasting blood glucose were analysed, and the meta-analysis revealed no significant difference between the two groups i.e. IF and control groups (SMD 0.06, 95% CI-0.25 to 0.38;p=0.69, I 2 =76%). Conclusion: IF and usual diet pattern have no difference in terms of glycaemic control. Although, IF may be used as a preventative diet pattern in the pre-diabetic population, as it works well in the long-term to achieve controlled sugar levels. Study registration: The protocol of this study was registered in The International Prospective Register of Systematic Reviews (PROSPERO) with a registration number CRD42022328528.
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Introduction: Obesity is a problem in almost all societies, leading to the search for different methods to combat it. One of them is intermittent fasting (IF), characterized by periods without food intake (16 to 24 hours), limited or no caloric intake, combined with normal eating windows. Objective: The study aims to determine the effectiveness of intermittent fasting on biochemical and anthropometric markers in obese adults. Methods: A systematic review was proposed that aimed to study blinded or open clinical trials of IF interventions, compared to the control group. The response variables were: systolic and diastolic blood pressure, total cholesterol, LDL, HDL, triglycerides, blood glucose, fat mass, weight, waist circumference, BMI, and heart rate. The search and identification of studies was masked. Risks of bias for the Cochrane Collaboration were assessed. They were subjected to meta-analysis (random effect), with R 4.0.0. Results: Six studies were included, of 10 to 48 weeks of intervention with alternate-day fasting and time-restricted feeding, reporting some statistically significant changes for different variables (specify). Conclusion: Intermittent fasting could intervene in the reduction of cardiovascular risk by improving BMI and biochemical parameters.
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Meal replacements and food supplements are now popular commercial weight loss and nutrition products. This review describes the efficacy, effectiveness, and therapeutic use of one such product - a soy-yoghurt-honey food formulation. The original formula of this product was created more than thirty years ago and since that time it has become well established as a food supplement supporting a healthy lifestyle. Therapeutic evidence for this product is based on numerous scientific studies and clinical trials, focusing particularly on weight management and associated metabolic risk factors and published as peer-reviewed articles. Given the availability of the product and the extent to which it has been experimentally evaluated, it is timely and important that the research is brought together under a single review to consolidate the understanding for the scientific and clinical communities. This review discusses the ingredients and the broad mechanisms of action, which are probably due to the biological properties of the three base components - soy, milk, and honey. It further summarizes and discusses the laboratory and clinical intervention studies, including the biochemical and metabolic mechanisms regarding the insulin- and lipid-lowering, anti-hypertensive, anti-inflammatory, antioxidant, and anti-microbial properties of the overall food and its base products.
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Background Intermittent fasting or calorie restriction (CR) diets provide anti-inflammatory and neuroprotective advantages in models of multiple sclerosis (MS); data in humans are sparse. Methods We conducted a randomised-controlled feeding study of different CR diets in 36 people with MS over 8 weeks. Participants were randomised to 1 of 3 diets: 1) a control diet, in which the participant received 100% of his or her calorie needs 7 days per week, 2) a daily CR diet, in which the participant received 78% of his or her calorie needs 7 days per week, or 3) an intermittent CR diet, in which the participant received 100% of his or her calorie needs on 5 days per week and 25% of his or her calorie needs 2 days per week (i.e., a “5:2” style diet). Untargeted metabolomics was performed on plasma samples at weeks 0, 4 and 8 at Metabolon Inc (Durham, NC). Flow cytometry of cryopreserved peripheral blood mononuclear cells at weeks 0 and 8 were used to identify CD3⁺;CD4⁺ (CD4⁺) and CD3⁺;CD4⁻ (as a proxy for CD8⁺) T cell subsets including effector memory, central memory, and naïve cells. Findings 31 (86%) completed the trial. Over time, individuals randomised to intermittent CR had significant reductions in effector memory (for CD4⁻EM: -3.82%; 95%CI: -7.44, -0.21; for CD4⁻: -6.96%; 95%CI: -11.96, -1.97) and Th1 subsets (-4.26%; 95% CI: -7.11, -1.40) and proportional increases in naïve subsets (for CD4⁻: 10.11%; 95%CI: 3.30, 16.92%). No changes were observed for daily CR or weight-stable diets. Larger within-person changes in lysophospholipid and lysoplasmalogen metabolites in intermittent CR were associated with larger reductions in memory T cell subsets and larger increases in naïve T cell subsets. Interpretation In people with MS, an intermittent CR diet was associated with reduction in memory T cell subsets and certain biologically-relevant lipid markers. Funding National MS Society, NIH, Johns Hopkins Catalyst Award.
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Caloric restriction is a popular approach to treat obesity and its associated chronic illnesses but is difficult to maintain for a long time. Intermittent fasting is an alternative and easily applicable dietary intervention for caloric restriction. Moreover, intermittent fasting has beneficial effects equivalent to those of caloric restriction in terms of body weight control, improvements in glucose homeostasis and lipid profiles, and anti-inflammatory effects. In this review, the beneficial effects of intermittent fasting are discussed.
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Background Type 2 Diabetes is a metabolic disorder characterized by hyperglycemia that causes numerous complications with significant long-term morbidity and mortality. The disorder is primarily due to insulin resistance particularly in liver, skeletal muscle, and adipose tissue. In this review, we detail the hormonal mechanisms leading to the development of diabetes and discuss whether intermittent fasting should be considered as an alternative, non-medicinal treatment option for patients with this disorder. Methods We searched PubMed, Ovid MEDLINE, and Google Scholar databases for review articles, clinical trials, and case series related to type 2 diabetes, insulin resistance, and intermittent fasting. Articles were carefully reviewed and included based on relevance to our topic. We excluded abstracts and any non-English articles. Results The majority of the available research demonstrates that intermittent fasting is effective at reducing body weight, decreasing fasting glucose, decreasing fasting insulin, reducing insulin resistance, decreasing levels of leptin, and increasing levels of adiponectin. Some studies found that patients were able to reverse their need for insulin therapy during therapeutic intermittent fasting protocols with supervision by their physician. Conclusion Current evidence suggests that intermittent fasting is an effective non-medicinal treatment option for type 2 diabetes. More research is needed to delineate the effects of intermittent fasting from weight loss. Physicians should consider educating themselves regarding the benefits of intermittent fasting. Diabetic patients should consult their physician prior to beginning an intermittent fasting regimen in order to allow for appropriate oversight and titration of the patients medication regimen during periods of fasting.
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Background Cardiovascular disease (CVD) is the leading cause of death worldwide. Lifestyle changes are at the forefront of preventing the disease. This includes advice such as increasing physical activity and having a healthy balanced diet to reduce risk factors. Intermittent fasting (IF) is a popular dietary plan involving restricting caloric intake to certain days in the week such as alternate day fasting and periodic fasting, and restricting intake to a number of hours in a given day, otherwise known as time‐restricted feeding. IF is being researched for its benefits and many randomised controlled trials have looked at its benefits in preventing CVD. Objectives To determine the role of IF in preventing and reducing the risk of CVD in people with or without prior documented CVD. Search methods We conducted our search on 12 December 2019; we searched CENTRAL, MEDLINE and Embase. We also searched three trials registers and searched the reference lists of included papers. Systematic reviews were also viewed for additional studies. There was no language restriction applied. Selection criteria We included randomised controlled trials comparing IF to ad libitum feeding (eating at any time with no specific caloric restriction) or continuous energy restriction (CER). Participants had to be over the age of 18 and included those with and without cardiometabolic risk factors. Intermittent fasting was categorised into alternate‐day fasting, modified alternate‐day fasting, periodic fasting and time‐restricted feeding. Data collection and analysis Five review authors independently selected studies for inclusion and extraction. Primary outcomes included all‐cause mortality, cardiovascular mortality, stroke, myocardial infarction, and heart failure. Secondary outcomes include the absolute change in body weight, and glucose. Furthermore, side effects such as headaches and changes to the quality of life were also noted. For continuous data, pooled mean differences (MD) (with 95% confidence intervals (CIs)) were calculated. We contacted trial authors to obtain missing data. We used GRADE to assess the certainty of the evidence. Main results Our search yielded 39,165 records after the removal of duplicates. From this, 26 studies met our criteria, and 18 were included in the pooled analysis. The 18 studies included 1125 participants and observed outcomes ranging from four weeks to six months. No studies included data on all‐cause mortality, cardiovascular mortality, stroke, myocardial infarction, and heart failure at any point during follow‐up. Of quantitatively analysed data, seven studies compared IF with ab libitum feeding, eight studies compared IF with CER, and three studies compared IF with both ad libitum feeding and CER. Outcomes were reported at short term (≤ 3 months) and medium term (> 3 months to 12 months) follow‐up. Body weight was reduced with IF compared to ad libitum feeding in the short term (MD ‐2.88 kg, 95% CI ‐3.96 to ‐1.80; 224 participants; 7 studies; low‐certainty evidence). We are uncertain of the effect of IF when compared to CER in the short term (MD ‐0.88 kg, 95% CI ‐1.76 to 0.00; 719 participants; 10 studies; very low‐certainty evidence) and there may be no effect in the medium term (MD ‐0.56 kg, 95% CI ‐1.68 to 0.56; 279 participants; 4 studies; low‐certainty evidence). We are uncertain about the effect of IF on glucose when compared to ad libitum feeding in the short term (MD ‐0.03 mmol/L, 95% CI ‐0.26 to 0.19; 95 participants; 3 studies; very‐low‐certainty of evidence) and when compared to CER in the short term: MD ‐0.02 mmol/L, 95% CI ‐0.16 to 0.12; 582 participants; 9 studies; very low‐certainty; medium term: MD 0.01, 95% CI ‐0.10 to 0.11; 279 participants; 4 studies; low‐certainty evidence). The changes in body weight and glucose were not deemed to be clinically significant. Four studies reported data on side effects, with some participants complaining of mild headaches. One study reported on the quality of life using the RAND SF‐36 score. There was a modest increase in the physical component summary score. Authors' conclusions Intermittent fasting was seen to be superior to ad libitum feeding in reducing weight. However, this was not clinically significant. There was no significant clinical difference between IF and CER in improving cardiometabolic risk factors to reduce the risk of CVD. Further research is needed to understand the safety and risk‐benefit analysis of IF in specific patient groups (e.g. patients with diabetes or eating disorders) as well as the effect on longer‐term outcomes such as all‐cause mortality and myocardial infarction.
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ይህን መጽሀፍ ለምን ለመተርጎም ወሰንኩ? እኔ ዶ/ር ዘውዱ ወንዲፍራው የደ/ማረቆስ ዩኒቨርስቲ ባለደረባ ስሆን በ2008 ዓ.ም ጥቅምት ወር መጀመሪያ አካባቢ ከፍተኛ የውሃ ጥም፣ በተደጋጋሚ ከፍተኛ መጠን ያለው ሽንት መሽናት፣ የሰውነት የድካም ስሜት፣ ብዥ የሚል ዕይታና የትኩረት ማጣት ችግሮች በአንድ ዕለት ሌሊት ተከሰቱብኝ፡፡ ዕለቱ እንደጠባ ጧት ሆስፒታል ሄድኩ የደም የስኳር መጠኔን ተመረመርኩ ምግብ ሳልወስድ 280 mg/dl ሆኖ አገኘሁት፡፡ በጣም የገረመኝ ከዚያ በፊት አንድም ቀን እንኳ ስለስኳር በሽታ አስቤ የቅድሚያ ምርመራ አለማድረጌ ነው፡፡ በወቅቱ የሰውነት ክብደቴ 82 ኪ.ግ ነበር፡፡ ቁመቴ 1 ሜትር ከ65 ሳ.ሜ ሲሆን በሰውነት ክብደት መረጃ ጠቋሚ መሰረት 30.12 ነበርኩ ይህም በሰውነት ክብደት ምደባዎች አማካኝነት ከልክ ያለፈ የሰውነት ውፍረት ነበረኝ ማለት ነው፡፡ ከምርመራ በኋላ ሁለት አይነት በአፍ የሚወሰዱ መድሃኒቶችን ማለትም ሜትፎርሚንና ዳይዎኔል የሚባሉትን መድሃኒቶችን እንድወስድ ሀኪሙ አዘዘልኝ፡፡ የታዘዙትን መድሃኒቶች ለ 10 ተካታታይ ቀናት ወስጄ አቋረጥኩ፡፡ ምክንያቱም አዕምሮዬ በፍጹም የህይወት ዘመን የስኳር በሽተኛ መሆንን ሊቀበለው አልቻለም፡፡ በምትኩ በሳምንት 4 ቀናት ለአንድ ስዓት ያህል ጠንከር ያለ የአካል ብቃት እንቅስቃሴ ለ4 ተከታታይ አመታት ያለማቋረጥ መስራት ጀመርኩ፡፡ በተጨማሪም ዝቅተኛ የካሮቦሃይድሬት ይዘት ያላቸውን ምግቦች ብቻ መመገብ ጀመርኩ እንዲሁም አልፎ አልፎ ጧት ላይ ቁርስ መብላቴን አቆምኩ፡፡ ምንም አይነት አልኮሆል መጠጣቴን አቋረጥኩ፡፡ በዚህም ምክንያት የደም ስኳሬ መጠን እየተስተካከለ መጣ ከመነሻው ከ280 mg/dl ወደ 114 mg/dl ወይም 5.6% የሂሞግሎቢን ኤዋንሲ የተረጋጋ ውጤት ደረሰ፡፡ የሰውነቴ ክብደት በአራት አመት ጊዜ ውስጥ 14 ኪ.ግ. በመቀነስ 68 ኪ.ግ. ደረሰ፡፡ አሁን የቀነስኩትንም ክብደት በዘለቄታው አስጠብቄያለሁ፡፡ በዕየለቱ በውስጤ ደስታና ቀለል የሚል ስሜት እንዲሁም የበለጠ የሰውነት ብርታትና ጥንካሬ ይሰማኛል፡፡ ከዚሁ እንቅስቃሴ ጎን ለጎን ስለ ስኳር በሽታ ከኢንተርኔት ላይ መጽሃፍትን፣ የምርምር ወረቀቶችን፣ ቪዲዮዎችን ማንበብና ማዳመጥ ጀመርኩ፡፡ እነዚህን ሁሉ መረጃዎች ሳገናዝብ የሁለተኛው አይነት የስኳር በሽታ ሊድን የሚችል በሽታ እንደሆነና በርካታ ሰዎችም ከበሽታው እንደተፈወሱ ብዙ መረጃዎችን ለማየት ሞከርኩ፡፡ በዚህ ረገድ ካናዳ ቶሮንቶ ከተማ ውስጥ ጥብቅ የሆነ የአመጋገብ ቁጥጥር በማድረግ የሁለተኛው አይነት የስኳር በሽታ ያለባቸውን ህሙማን የሚያክም ዶ/ር ጀሰን ፈንግ የሚባል የኩላሊት ሀኪም መኖሩን ከድረ-ገጽ መረጃ አገኘሁ፡፡ እርሱም በዚሁ በሽታ ዙሪያ በርካታ የህዝብ ንግግሮችን ያደረገ ሲሆን መጽሃፍትንም ጽፏል፡፡ እርሱ ከጻፋቸው መጽሃፍት ውስጥ The-Diabetes-Code and The-Obesity-Code ዋናዎቹ ናቸው፡፡ ስለሆነም The-Diabetes-Code የተሰኘውን መጽሃፍ በዶ/ር ሩቅያ ሀሰን አማካኝነት ወደ አማርኛ “የስኳር በሽታ ቁልፍ” በሚል ርዕስ ተተርጉሞ አሁን በኢትዮጵያ ገበያ ላይ የሚገኝ ሲሆን እኔም በእርሷ የስራ ትጋት መነሻነት The-Obesity-Code የሚለውን መጽሃፍ ወደ አማርኛ “የሰውነት ውፍረትን የሚያመጡ ሚስጥራዊ እውነታዎች” በሚል ርዕስ ለመተርጎም ወሰንኩ፡፡ ይህ መጽሃፍ አማዞን በተሰኘው የድረ ገጽ መጽሃፍ መደብር ውሰጥ ከፍተኛ ሽያጭ ያሰገኘ ሲሆን እኔም ለኢትዮጵያዊያን ወገኖቼ በሚረዱት ቋንቋ ቢቀርብላቸው በርካቶች እንደእኔ ሊጠቀሙበት ይችላሉ ብዬ በማሰብ ለመተርጎም ችያለሁ፡፡ በዚህ መጽሃፍ ውስጥ ለሁለተኛው አይነት የስኳር በሽታ መሰረታዊ መንስኤ ከልክ ያለፈ የሰውነት ውፍረት መሆኑን ዶ/ር ፈንግ በዝርዝር ያስረዳል፡፡ ስለሆነም ምክንያታዊ በሆነ መልኩ የሰውነት ውፍረት ወሳኝ ትኩረት ያስፈልገዋል የሚል እምነት አለው፡፡ ብሎም ከልክ ያለፈ የሰውነት ውፍረት እና ሁለተኛው ዓይነት የስኳር በሽታ ብዙ ጠቃሚ የሆኑ ተመሳሳነትና ልዩነት እንዳላቸው ያሳያል፡፡ ኢንሱሊን በሰውነት ክብደት ውስጥ ያለውን ማዕከላዊ ሚና እንዲሁም የሰውነት የኢንሱሊን መቋቋም ችግር በሰውነት ክብደት ውስጥ የሚጫወተውን ወሳኝ ሚና በሚገባ ያስረዳል፡፡ በመጽኃፉም የሰውነት የኢንሱሊን መጠን የመጨመር ችግርን በመቆጣጠር ከልክ ያለፈ የሰውነት ውፍረትን መከላከል የሚያስችሉ መመሪያዎችን ይሰጣል፡፡ የአመጋገብ መመሪያዎች ኢንሱሊንን ለመቀነስ በተለይ የስኳር እና የተጣሩ የሰብል ውጤቶችን በመቀነስ፤ የፕሮቲንን ፍጆታ የተመጣጠነ እንዲሆን በማድረግ እና የጤናማ ስብ እና የአሰርን ፍጆታ በመጨመር ማስተካከል እንደሚቻል ይገልጸል፡፡ የካሎሪ ቅነሳ በሰውነት ጤንነት ላይ አሉታዊ ተጽዕኖ ሳያስከትል ጠንካራ ጾም በመጾም የሰውነት የኢንሱሊን የመቋቋም ችግር የሚያሰከትለውን አሉታዊ የሆነ ወሳኝ ሚና ለማስተካከል ውጤታማ መንገድ መሆኑን ያስረዳል፡፡ በመጽሐፉ ውስጥ ደራሲው በሰዎች ላይ የተደረጉ ጥናቶችን እና በአብዛኛው በታዋቂ ባለሙያዎች ተገምግመው በከፍተኛ ጥራት በሚታወቁ ጆርናሎች የታተሙትን ከ450 በላይ የምርምር ግኝቶችን እንደዋቢነት ተጠቅሟል፡፡ ስለሆነም ለኢትዮጵያዊያን ወገኖቼ መግለጽ የምፈልገው ይህ መጽሃፍ የእኔን ተስፋና ህይወት ቀይሮታል በዚህም መሰረት ይህ ችግር ያለባቸውን ሰዎች ህይወት ይቀይራል ብየ በጽኑ አምናለሁ፡፡ ስለዚህ ከልክ ያለፈ የሰውነት ውፍረትና የሁለተኛው አይነት የስኳር በሽታ ያላባቸውም ሆነ የሌለባቸው ሰዎች መጽሃፉን አግኝተው ቢያነቡት ብዙ ጠቃሚ መረጃ ያገኛሉ ብዬ በእጅጉ አምናለሁ፡፡
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Parity nonconservation (PNC) was studied for 24 p-wave neutron resonances in U-238 from 10 to 300 eV by measuring the helicity dependence of the total neutron cross section with an improved experimental apparatus. Six resonances show statistically significant (greater than 2.9 sigma) parity violation. An analysis treating the PNC matrix elements as random variables yields a root-mean-square PNC matrix element M = 0.671(-0.16)(+0.24) meV. The corresponding weak spreading width Gamma(w) = (1.35(-0.64)(+0.97)) x 10(-7) eV.
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To investigate whether normal glucose-tolerant and type II diabetic overweight adults differ in response to weight regain with regard to substrate oxidation and metabolic parameters. A total of 15 overweight-obese subjects: seven normal glucose tolerant (NGT) and eight with type II diabetes (DM) were restudied 5 y after significant weight loss. Prediet, after 28 days calorie restriction and at 5 y, subjects were characterised for weight, height, waist-to-hip ratio (WHR) and body composition by dual-energy X-ray absorptiometry. Fasting glucose, insulin, leptin and lipid levels were measured and subjects underwent euglycaemic-hyperinsulinaemic clamp (insulin 0.25 U/kg/h for 150 min). Indirect calorimetry was performed resting and in the final 30 min of the clamp. Dietary assessment was by 4-day diet-diary. Both NGT and DM groups regained weight at 5 y and were not different to prediet. Total body fat (%) and WHR were higher at 5 y compared to prediet in both groups. Fasting glucose was increased in NGT subjects at 5 y, and fasting insulin was higher in both groups at 5 y compared to prediet. Insulin sensitivity (GIR) was similar at 5 y compared to prediet, but at 5 y DM subjects were more insulin resistant than NGT subjects. At 5 y, both DM and NGT groups had significantly reduced basal fat oxidation and no significant suppression of fat oxidation with insulin. Clamp respiratory quotient levels at 5 y were significantly higher in NGT compared to DM subjects. Reduced basal fat oxidation, and reduced variation in substrate oxidation in response to insulin develop with fat regain and fasting hyperinsulinaemia in both NGT and DM obese adults.
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Dietary restriction (DR) has been shown to increase life span, delay or prevent age-associated diseases, and improve functional and metabolic cardiovascular risk factors in rodents and other species. To investigate the effects of DR on beat-to-beat heart rate and diastolic blood pressure variability (HRV and DPV) in male Sprague-Dawley rats, we implanted telemetric transmitters and animals were maintained on either intermittent fasting (every other day feeding) or calorie-restricted (40% caloric reduction) diets. Using power spectral analysis, we evaluated the temporal profiles of the low- and high-frequency oscillatory components in heart rate and diastolic blood pressure signals to assess cardiac autonomic activity. Body weight, heart rate, and systolic and diastolic blood pressure were all found to decrease in response to DR. Both methods of DR produced decreases in the low-frequency component of DPV spectra, a marker for sympathetic tone, and the high-frequency component of HRV spectra, a marker for parasympathetic activity, was increased. These parameters required at least 1 month to become maximal, but returned toward baseline values rapidly once rats resumed ad libitum diets. These results suggest an additional cardiovascular benefit of DR that merits further studies of this potential effect in humans.
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Adiponectin is an abundant serum adipokine secreted exclusively from differentiated adipocytes, which plays an important role in regulating insulin sensitivity. The dynamics of circulating adiponectin concentrations have yet to be systematically investigated. We sought to determine whether serum adiponectin levels exhibit diurnal or ultradian rhythms in healthy normal-weight men and to compare the 24-h profile of adiponectin fluctuations with those of leptin, leptin-binding protein (sOB-R), and cortisol. We collected blood samples at 15-min intervals over 24 h from six subjects receiving an isocaloric diet, and we measured adiponectin, leptin, sOB-R, and cortisol levels. Fourier and cross-correlation analyses were performed on these time series to study diurnal variations, and the Cluster7 program was used for pulsatility analysis. Circulating adiponectin and sOB-R levels exhibited ultradian pulsatility as well as a diurnal variation with a significant decline at night, reaching a nadir in the early morning. The 24-h variations of serum adiponectin and sOB-R were nearly identical and followed those of cortisol after a few hours, but were out-of-phase with leptin diurnal rhythms. These data suggest that adiponectin and sOB-R levels might be influenced by common regulatory factors and challenge the notion that cortisol may have a direct inhibitory effect on adiponectin in humans.
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The role of resistin in insulin sensitivity and obesity is controversial. Some authors suggest that increased serum resistin levels are associated with obesity, visceral fat, insulin resistance, type 2 diabetes and inflammation, while others failed to observe such correlations. The aim of the present study was to investigate the relationship of plasma resistin levels with markers of the metabolic syndrome and atherosclerosis in a large population-based study. Plasma resistin levels were determined in 1090 subjects free of any medication selected from the PLIC study (designed to verify the presence of atherosclerotic lesions and progression intima-media thickness (IMT) in the common carotid artery in the general population) and related to the presence of obesity, metabolic syndrome, metabolic abnormalities, cardiovascular risk, and progression of IMT. Plasma resistin levels were highly positively correlated with triglycerides, waist circumference, waist/hip ratio, systolic blood pressure, and ApoAI/ApoB ratio, while they were inversely correlated with high density lipoprotein and ApoAI levels. This finding was gender specific (mainly in women). Plasma resistin levels were significantly higher in women with the metabolic syndrome compared with controls (4.90 (0.24) ng/ml vs 3.90 (0.11) ng/ml; P<0.01), while no difference was observed in obese subjects. Finally, plasma resistin levels were significantly correlated with cardiovascular risk calculated according to the Framingham algorithm (P<0.01). Plasma resistin levels are increased in presence of the metabolic syndrome and are associated with increased cardiovascular risk.
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An epidemic of overweight/obesity and type 2 diabetes, caused by overeating nutrient-poor energy-dense foods and a sedentary lifestyle, is spreading rapidly throughout the world. Abdominal obesity represents a serious threat to health because it increases the risk of developing many chronic diseases, including cardiovascular disease and cancer. Calorie restriction (CR) with adequate nutrition improves cardiometabolic health, prevents tumorigenesis and increases life span in experimental animals. The purpose of this review is to evaluate the metabolic and clinical implications of CR with adequate nutrition in humans, within the context of data obtained in animal models. It is unlikely that information regarding the effect of CR on maximal life span in humans will become available in the foreseeable future. In young and middle-aged healthy individuals, however, CR causes many of the same cardiometabolic adaptations that occur in long-lived CR rodents, including decreased metabolic, hormonal and inflammatory risk factors for diabetes, hypertension, cardiovascular disease and cancer. Unraveling the mechanisms that link calorie intake and body composition with metabolism and aging will be a major step in understanding the age-dependency of a wide range of human diseases and will also contribute to improve the general quality of life at old ages.
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Parity nonconservation was studied for seventeen states in {sup 239}U by measuring the helicity dependence of the total cross section for epithermal neutrons scattered from {sup 238}U. The root-mean-squared parity-violating matrix element for the mixing of {ital p}-wave and {ital s}-wave states was determined to be {ital M}=0.58{sub {minus}0.25}{sup +0.50} meV. This corresponds to a parity-violating spreading width of {Gamma}{sup PV}=1.0{times}10{sup {minus}7} eV. Under plausible assumptions this gives a value of 4{times}10{sup {minus}7} for {vert bar}{alpha}{sub {ital P}}{vert bar}, the ratio of strengths of the {ital P}-odd and {ital P}-even effective nucleon-nucleon interactions.
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The relation between alternate-day fasting (ADF) and cardioprotection remains uncertain. In the present study, we examined the ability of modified ADF, with a low-fat (LF) vs high-fat (HF) background diet, to modulate adipose tissue physiology in a way that may protect against coronary heart disease. In a 4-week study, male C57BL/6 mice were randomized to 1 of 3 groups: (1) ADF-85%-LF (85% energy restriction on fast day, ad libitum fed on feed day, on an LF diet), (2) ADF-85%-HF (same protocol but HF diet), and (3) control (ad libitum fed). Throughout the study, body weight did not differ between ADF and control animals. Proportion of subcutaneous fat increased (P < .01), whereas the proportion of visceral fat decreased (P < .01), in both ADF groups. Triglyceride (TG) synthesis was augmented (P < .05) in subcutaneous fat, but remained unchanged in visceral fat. Adiponectin concentrations were elevated (P < .05), whereas leptin and resistin levels decreased (P < .05). Aortic vascular smooth muscle cell proliferation was reduced (P < .05) by 60% and 76% on the LF and HF diets, respectively. Plasma total cholesterol, TG, and free fatty acid concentrations also decreased (P < .05). In summary, modified ADF regimens alter adipose tissue physiology (ie, body fat distribution, TG metabolism, and adipokines) in a way that may protect against coronary heart disease. These beneficial effects were noted over a wide range of fat intake, suggesting that ADF may be protective even in the presence of HF diets.
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Nearly 1 in 4 adults in the United States is obese. The connection between obesity and insulin resistance, type 2 diabetes, and cardiovascular disease is a well researched one. The increasing prevalence of each of these diseases has become a growing concern for the medical community. Adiponectin is a collagen-like plasma protein secreted by adipocytes that has been suggested to play a causal role in the development of insulin resistance and cardiovascular disease. The protein has been found to be decreased in cases of insulin resistance, diabetes, atherosclerosis, and coronary artery disease. Up-regulation of adiponectin and its receptor, through the use of thiazolidinediones, has been found to be partially related to insulin sensitization and thus antidiabetic effects. In this review, we discuss adiponectin's antiatherogenic effects, its association with insulin resistance and obesity, and the possibility of using adiponectin and its receptor as a therapeutic target.
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This study sought to better determine the link between leptin and coronary heart disease (CHD). Circulating leptin is considered a risk factor for CHD but larger studies are needed. Leptin levels were measured in 550 men with fatal CHD or nonfatal myocardial infarction and in 1,184 controls nested within a prospective study of 5,661 British men and set in context with a meta-analysis. Baseline leptin correlated with body mass index (BMI), blood pressure, total cholesterol, triglyceride, and inflammatory markers; correlations persisted after BMI adjustment. The within-person consistency of leptin values over 4 years (correlation coefficient: 0.79; 95% confidence interval [CI]: 0.73 to 0.83) was higher than those of some established cardiovascular risk factors. In a comparison of individuals in the top third with those in the bottom third of baseline leptin, the age- and town-adjusted odds ratio for CHD was 1.25 (95% CI: 0.96 to 1.62), decreasing to 0.98 (95% CI: 0.72 to 1.34) after adjustment for BMI. A systematic review identified 7 prospective reports with heterogeneous findings (I(2) = 60%, 13% to 82%). The combined adjusted risk ratio across all studies was 1.44 (95% CI: 0.95 to 2.16) in a comparison of extreme thirds of leptin levels. The inconsistency between studies was partially explained by sample size, with combined estimates from studies involving >100 CHD cases (1.28, 95% CI: 0.80 to 2.04) being somewhat weaker than those from smaller studies (1.81, 95% CI: 0.76 to 4.31). Previous studies appear to have overestimated associations of leptin and CHD risk. Our results suggest a moderate association that is largely dependent on BMI.
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Atherosclerotic coronary heart disease (CHD) is the most common cause of morbidity and mortality among men and women in developed nations. The obesity epidemic contributes to the increasing prevalence of high blood sugar (as may be found in patients with diabetes mellitus and metabolic syndrome), high blood pressure, and dyslipidemia--all CHD risk factors. Metabolic syndrome describes the common clinical finding wherein component CHD risk factors cluster within a single patient, but this term does not identify any unified pathophysiologic process. However, a component of the metabolic syndrome is abdominal obesity, which does reflect an anatomic manifestation of a "common-soil" pathophysiologic process that promotes the onset of CHD risk factors, and thus increases CHD risk. Adiposopathy ("sick fat") is anatomically characterized by visceral adiposity and adipocyte hypertrophy; it is manifested physiologically by a net increase in release of free fatty acids and by pathogenic adipose tissue metabolic/immune responses that promote metabolic disease and increase CHD risk. Understanding the relation of adiposopathy to CHD risk factors and recognizing the importance of treating both the "cause and effect" of metabolic diseases are critical toward a comprehensive approach in reducing CHD risk. Regarding the "cause," clinicians and their patients should be diligent regarding appropriate nutritional and lifestyle interventions that may favorably affect health. Regarding the "effect," clinicians and their patients should be equally diligent toward appropriate pharmaceutical interventions that reduce CHD risk factors when nutritional and lifestyle interventions do not sufficiently achieve desired metabolic treatment goals.
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The last 20 years have witnessed dramatic reductions in cardiovascular risk using 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ("statins") to lower levels of low-density lipoprotein cholesterol (LDL-C). Using this approach one can achieve a reduction in the risk of major cardiovascular events of 21% for every 1 mmol/l (39 mg/dl) decrease in LDL-C. However, despite intensive therapy with high dose "statins" to lower LDL-C levels below 2.6 mmol/l (100 mg/dl), the risk of a major cardiovascular event in patients with established coronary artery disease remains significant at a level approaching an annual risk of 9%, paving the way for new strategies for reducing the residual cardiovascular risk in this patient group. Early epidemiological studies have identified low levels of high-density lipoprotein cholesterol (HDL-C) (<1.0 mmol/l or 40 mg/dl), a common feature of type 2 diabetes mellitus and the metabolic syndrome, to be an independent determinant of increased cardiovascular risk. The beneficial effects of HDL-C on the cardiovascular system have been attributed to its ability to remove cellular cholesterol, as well as its anti-inflammatory, antioxidant and antithrombotic properties, which act in concert to improve endothelial function and inhibit atherosclerosis, thereby reducing cardiovascular risk. As such, raising HDL-C in patients with aggressively lowered LDL-C provides an additional strategy for addressing the residual cardiovascular risk present in these patients groups. Studies suggest that for every 0.03 mmol/l (1.0 mg/dl) increase in HDL-C, cardiovascular risk is reduced by 2-3%. Raising HDL-C can be achieved by both lifestyle changes and pharmacological means, the former of which include smoking cessation, aerobic exercise, weight loss and dietary manipulation. Therapeutic strategies have included niacin, fibrates, thiazolidinediones and bile acid sequestrants. Newly developed pharmacological agents include apolipoprotein A-I mimetics and the cholesteryl ester transfer protein (CETP) inhibitors, JTT-705 and torcetrapib, the latter of which has been recently withdrawn from clinical testing because of serious adverse effects. Emerging experimental studies investigating the complex pathways of HDL metabolism have identified several new targets for raising HDL-C with new pharmaceutical agents currently in development. For the time being, the long-acting formulations of nicotinic acid remain the most effective and best tolerated pharmacological strategy for raising HDL-C in patients already on statin therapy to control LDL-C. Therefore, raising HDL-C represents an important strategy for reducing residual cardiovascular risk in patients already optimally treated with statins, and should lead to further improvements in clinical outcomes in these patient groups.
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Despite decades of research, the question as to whether coffee intake increases the risk of coronary heart disease (CHD) remains controversial. In the current paper, we discuss the acute and long-term cardiovascular effects of coffee, and its major constituents, which could underlie such an association. Experimental studies have shown that administration of coffee or caffeine acutely raises blood pressure, circulating concentrations of (nor)epinephrine, increases arterial stiffness, impairs endothelium dependent vasodilation and inhibits ischemic preconditioning. The adverse effects of chronic coffee consumption on traditional risk factors for CHD are less consistent: although coffee intake slightly increases blood pressure, and plasma concentrations of homocysteine and cholesterol, there is no association with the incidence of hypertension, and a strong negative association with the incidence of type 2 diabetes mellitus. Moreover, common polymorphisms in genes involved in the metabolism of caffeine, catecholamines, homocysteine, and cholesterol can modulate the effect of coffee intake on cardiovascular parameters. Many epidemiological studies have explored the association between coffee drinking and CHD. Most prospective studies have not shown a positive association, whereas case-control studies in general have reported such an association. This discrepancy could be explained by an acute adverse effect of coffee, rather than a long-term adverse effect. We postulate that coffee drinking may have an acute detrimental effect in triggering coronary events and increasing infarct size in selected patient groups, rather than promoting the development of atherosclerosis in the general population, and we propose an alternative approach to explore such an effect in epidemiological studies.
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Obesity is considered a low-grade chronic inflammatory condition as reflected by increased C-reactive protein (CRP) levels. Inflammation is emerging as a predictor of cardiovascular disease and it may be a precursor of the metabolic syndrome. Bariatric surgery is commonly performed as a treatment for morbid obesity offering significant reductions in premature myocardial infarction. Laparoscopic sleeve gastrectomy (LSG) is a relatively new bariatric procedure that is currently used as a definitive procedure for weight loss. The aim of this study is to assess the impact of sleeve gastrectomy on CRP levels. This study is part of an ongoing, prospective, cohort study to evaluate LSG impact on iron indices. CRP levels were compared preoperatively and 6 months after surgery. Similarly, demographics including body mass index and excess weight were also compared at these same study points. Data were analyzed using Student paired t test and Pearson product moment correlation analysis. Twenty-nine morbidly obese patients were included. There was significant decrease in body mass index (BMI) between the preoperative and 6-month period (50.9 +/- 13.2 and 35.1 +/- 6.85, respectively; P < 0.001). Also CRP levels were statistically significantly lower at 6 months after surgery (preoperative 12.3 +/- 7.53 mg/L and postoperative 5.6 +/- 4.2 mg/L. P < 0.0001). The significant weight loss as reflected by change in BMI was correlated with the difference between preoperative and postoperative CRP levels. Massive weight loss in morbidly obese patients induced by LSG causes a significant decrease in CRP levels, which could reduce the risk of cardiovascular diseases in these patients.
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The effects of acute caloric restriction on cholesterol balance and kinetics of plasma cholesterol specific activity were investigated in five hyperlipemic subjects with varying degrees of obesity. Caloric restriction decreased plasma triglycerides by 41 +/- 12%, plasma cholesterol by 11 +/- 9%, and the ratio of esterified to free cholesterol by 12 +/- 7+. Immediately on institution of caloric restriction there appeared to be an influx of tissue cholesterol into plasma and a reduction in endogenous synthesis of cholesterol. The cholesterol balance decreased from 1,469 +/- 441 to 1,212 +/- 349 mg/day and the rate of decay of plasma cholesterol specific activity decreased 62 +/- 3%. The effect of caloric restriction on hepatic synthesis of bile acids was also very prompt. The total fecal bile acids were reduced immediately by 36 +/- 7%. Because the effect on fecal excretion of deoxycholic acid was greater than that on fecal lithocholic acid, it was suggested that hepatic synthesis of cholic acid was reduced more than the synthesis of chenodeoxycholic acid. Caloric restriction did not cause any change in the percentage of absorption of dietary cholesterol (40 +/- 2% versus 42 +/- 3%). These observations are in accord with our model relating cholesterol metabolism with the metabolism of plasma lipoproteins in man.
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A predictive equation for resting energy expenditure (REE) was derived from data from 498 healthy subjects, including females (n = 247) and males (n = 251), aged 19-78 y (45 +/- 14 y, mean +/- SD). Normal-weight (n = 264) and obese (n = 234) individuals were studied and REE was measured by indirect calorimetry. Multiple-regression analyses were employed to drive relationships between REE and weight, height, and age for both men and women (R2 = 0.71): REE = 9.99 x weight + 6.25 x height - 4.92 x age + 166 x sex (males, 1; females, 0) - 161. Simplification of this formula and separation by sex did not affect its predictive value: REE (males) = 10 x weight (kg) + 6.25 x height (cm) - 5 x age (y) + 5; REE (females) = 10 x weight (kg) + 6.25 x height (cm) - 5 x age (y) - 161. The inclusion of relative body weight and body-weight distribution did not significantly improve the predictive value of these equations. The Harris-Benedict Equations derived in 1919 overestimated measured REE by 5% (p less than 0.01). Fat-free mass (FFM) was the best single predictor of REE (R2 = 0.64): REE = 19.7 x FFM + 413. Weight also was closely correlated with REE (R2 = 0.56): REE = 15.1 x weight + 371.
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A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf- 0.20)is presented. The method involves measure- ments of fasting plasma total cholesterol, tri- glyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Cornparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99, de- pending on the patient population compared. Additional Keyph rases hyperlipoproteinemia classifi- cation #{149} determination of plasma total cholesterol, tri- glyceride, high-density lipoprotein cholesterol #{149} beta lipo proteins
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Among the many adipocyte-derived endocrine factors, we recently found an adipocyte-specific secretory protein, adiponectin, which was decreased in obesity. Although obesity is associated with increased cardiovascular mortality and morbidity, the molecular basis for the link between obesity and vascular disease has not been fully clarified. The present study investigated whether adiponectin could modulate endothelial function and relate to coronary disease. For the in vitro study, human aortic endothelial cells (HAECs) were preincubated for 18 hours with the indicated amount of adiponectin, then exposed to tumor necrosis factor-alpha (TNF-alpha) (10 U/mL) or vehicle for the times indicated. The adhesion of human monocytic cell line THP-1 cells to HAECs was determined by adhesion assay. The surface expression of vascular cell adhesion molecule-1 (VCAM-1), endothelial-leukocyte adhesion molecule-1 (E-selectin), and intracellular adhesion molecule-1 (ICAM-1) was measured by cell ELISA. Physiological concentrations of adiponectin dose-dependently inhibited TNF-alpha-induced THP-1 adhesion and expression of VCAM-1, E-selectin, and ICAM-1 on HAECs. For the in vivo study, the concentrations of adiponectin in human plasma were determined by a sandwich ELISA system that we recently developed. Plasma adiponectin concentrations were significantly lower in patients with coronary artery disease than those in age- and body mass index-adjusted control subjects. These observations suggest that adiponectin modulates endothelial inflammatory response and that the measurement of plasma adiponectin levels may be helpful in assessment of CAD risk.
Article
This paper reviews the general mechanisms by which leptin acts as a regulator of lipid reserves through changes in food intake, energy expenditure and fuel selection, with an emphasis on its direct effects on cellular lipid metabolism. Briefly, when leptin levels increase, food consumption decreases via modulation of hypothalamic neuropeptides. As well, normal decreases in energy expenditures (e.g. with diurnal cycles or reduced caloric intake) do not occur. This is probably caused by an increase in mitochondrial proton leak mediated by leptin via increases in sympathetic nervous system stimulation and thyroid hormone release. The decrease in caloric input coupled with relatively higher energy expenditure, therefore, leads to negative energy balance. Leptin also changes the fuel source from which ATP is generated. Fuel preference switches from carbohydrate (glucose) to lipid (fatty acids). This effect arises through stimulation of triacylglycerol catabolism by leptin. In vitro studies show that leptin is a potent stimulator of lipolysis and fatty acid oxidation in adipocytes and other cell types. Consequently, leptin is also a regulator of cellular triacylglycerol content. Hormonal regulation of leptin, as well as its role in fasting and seasonal weight gain and energy expenditure are also briefly discussed.
Article
Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes.
Article
Hypertension and insulin resistance syndrome are risk factors for cardiovascular disease, and it is therefore important to identify interventions that can reduce blood pressure and improve glucose metabolism. We performed experiments aimed at determining whether intermittent fasting (IF) can improve cardiovascular health and also tested the hypothesis that beneficial effects of IF can be mimicked by dietary supplementation with 2-deoxy-D-glucose (2DG) a non-metabolizable glucose analog. Four-month-old male rats were implanted with telemetry probes to allow continuous monitoring of heart rate, blood pressure, physical activity, and body temperature. Rats were then maintained for 6 months on one of three different dietary regimens: ad libitum feeding, IF, or 2DG supplementation. Rats on the IF regimen consumed 30% less food over time and had reduced body weights compared with rats fed ad libitum, whereas rats on the 2DG regimen did not reduce their food intake and maintained their body weight. Heart rate and blood pressure were significantly decreased within 1 month in rats on IF and 2DG diets and were maintained at reduced levels thereafter. Body temperature was significantly decreased in group IF, but not in group 2DG. Levels of serum glucose and insulin were significantly decreased in rats maintained on IF and 2DG-supplemented diets, suggesting that IF and 2DG diets affect insulin sensitivity in a similar manner. Finally, rats in groups IF and 2DG exhibited increased levels of plasma adrenocorticotropin and corticosterone, indicating that these diets induced a stress response. We conclude that reductions in blood pressure, heart rate, and insulin levels, similar to or greater than those obtained with regular physical exercise programs, can be achieved by IF and by dietary supplementation with 2DG by a mechanism involving stress responses.
Article
Resistin, an adipocyte-derived cytokine linked to insulin resistance and obesity, has recently been shown to activate endothelial cells (ECs). Using microarrays, we found that along with numerous other pro-atherosclerotic genes, resistin expression levels are elevated in the aortas of C57BL/6J apoE-/- mice; these findings led us to further explore the relation between resistin and atherosclerosis. Using TaqMan PCR and immunohistochemistry, we found that ApoE-/- mice had significantly higher resistin mRNA and protein levels in their aortas, and elevated serum resistin levels, compared to C57BL/6J wild-type mice. Incubation of murine aortic ECs with recombinant resistin increased monocyte chemoattractant protein (MCP)-1 and soluble vascular cell adhesion molecule (sVCAM)-1 protein levels in the conditioned medium. Furthermore, human carotid endarterectomy samples stained positive for resistin protein, while internal mammary artery did not show strong staining. Patients diagnosed with premature coronary artery disease (PCAD) were found to have higher serum levels of resistin than normal controls. In summary, resistin protein is present in both murine and human atherosclerotic lesions, and mRNA levels progressively increase in the aortas of mice developing atherosclerosis. Resistin induces increases in MCP-1 and sVCAM-1 expression in murine vascular endothelial cells, suggesting a possible mechanism by which resistin might contribute to atherogenesis. Finally, PCAD patients exhibited increased serum levels of resistin when compared to controls. These findings suggest a possible role of resistin in cardiovascular disease.
Article
Asthma is an increasingly common disorder responsible for considerable morbidity and mortality. Although obesity is a risk factor for asthma and weight loss can improve symptoms, many patients do not adhere to low calorie diets and the impact of dietary restriction on the disease process is unknown. A study was designed to determine if overweight asthma patients would adhere to an alternate day calorie restriction (ADCR) dietary regimen, and to establish the effects of the diet on their symptoms, pulmonary function and markers of oxidative stress, and inflammation. Ten subjects with BMI>30 were maintained for 8 weeks on a dietary regimen in which they ate ad libitum every other day, while consuming less than 20% of their normal calorie intake on the intervening days. At baseline, and at designated time points during the 8-week study, asthma control, symptoms, and Quality of Life questionnaires (ACQ, ASUI, mini-AQLQ) were assessed and blood was collected for analyses of markers of general health, oxidative stress, and inflammation. Peak expiratory flow (PEF) was measured daily on awakening. Pre- and postbronchodilator spirometry was obtained at baseline and 8 weeks. Nine of the subjects adhered to the diet and lost an average of 8% of their initial weight during the study. Their asthma-related symptoms, control, and QOL improved significantly, and PEF increased significantly, within 2 weeks of diet initiation; these changes persisted for the duration of the study. Spirometry was unaffected by ADCR. Levels of serum beta-hydroxybutyrate were increased and levels of leptin were decreased on CR days, indicating a shift in energy metabolism toward utilization of fatty acids and confirming compliance with the diet. The improved clinical findings were associated with decreased levels of serum cholesterol and triglycerides, striking reductions in markers of oxidative stress (8-isoprostane, nitrotyrosine, protein carbonyls, and 4-hydroxynonenal adducts), and increased levels of the antioxidant uric acid. Indicators of inflammation, including serum tumor necrosis factor-alpha and brain-derived neurotrophic factor, were also significantly decreased by ADCR. Compliance with the ADCR diet was high, symptoms and pulmonary function improved, and oxidative stress and inflammation declined in response to the dietary intervention. These findings demonstrate rapid and sustained beneficial effects of ADCR on the underlying disease process in subjects with asthma, suggesting a novel approach for therapeutic intervention in this disorder.
Article
Resistin is an adipocytokine belonging to the family of cysteine rich secretory proteins. We sought to determine if a correlation between resistin levels and carotid atherosclerosis exists in hypertensive patients. This study consisted of 307 treated hypertensive patients. Subjects were grouped into tertiles according to their resistin level. Carotid intima media thickness (IMT) was significantly highest in the third tertile. The first tertile had a mean carotid IMT and a mean of maximum carotid IMT of 0.63+/-0.08 and 0.81+/-0.10 mm, respectively. The 2nd tertile had measurements of 0.63+/-0.08 and 0.81+/-0.12 mm, and the 3rd tertile 0.67+/-0.12 and 0.86+/-0.11 for the same parameters. (p=0.002). Resistin levels were independently associated with the carotid IMT (mean carotid IMT: R(2)=0.159, p<0.001 and mean of maximum carotid IMT: R(2)=0.162, p<0.001) after controlling for age, gender, HDL cholesterol, triglyceride, LDL cholesterol, smoking and DM. The tertile level of resistin was significantly associated with (odds ratio=3.097, p=0.004) risk of coronary artery disease after controlling for age, gender, HDL cholesterol, triglyceride, LDL cholesterol, smoking, DM and carotid IMT. Serum resistin is independently associated with increasing carotid IMT in treated hypertensive patients.