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Weight loss, improved physical performance, cognitive function, eating behavior and metabolic profile in a 12-week ketogenic diet in obese adults

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Abstract

The ketogenic diet (KD) is being increasingly promoted as a strategy to fight obesity. Although the KD is effective for weight loss and weight control, comprehensive determination of its relationship with biochemical, physiological and psychological changes is still largely unexplored. We hypothesized that a 12-week KD (12KD) would significantly affect body weight, physical performance, cognitive function, eating behaviors, the metabolic and hormonal profile in obese adults, although differently in men and women. In an uncontrolled intervention, 35 sedentary obese adults (13 men, 25 women), aged 37 ± 7 years with a BMI 36.1 ± 5.6 kg/m2 underwent a 12KD between March 2017 and June 2017 at the University of Primorska. The 12KD resulted in decreased appetite, significant weight loss of participants (−18 ± 9 kg men vs. -11 ± 3 kg women; P < .001), decreased emotional and external eating (P < .001 for both), increased body image satisfaction (P < .001) and improved physical performance (P < .001). Biochemically, a significant drop in glucose (P = .026), and a significant increase in LDL-cholesterol (P = .031), CRP (P = .007), and BDNF (P = .035) were observed in the first 2 weeks; then, all listed parameters returned to baseline. On the other hand, a significant reduction in insulin (P < .001) and leptin levels (P < .001), and a significant increase in adiponectin (P = .008) and NPY (P = .009) were detected throughout the duration of the 12KD. Our results show the efficacy of the 12KD on weight loss, physical performance, cognitive function, eating behaviors and metabolic profile. However, the long-term effects of a KD on these outcomes needs to be further studied before general recommendations can be made.

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... A ketogenic diet consists of a very low-carbohydrate and highfat diet. This diet has gained popularity due to its favorable cardiovascular benefits, including rapid weight loss, decrease in serum hemoglobin A1c, and decrease in total cholesterol [19][20]. This diet has also been shown to be beneficial for patients on polydrug therapy for seizure disorders, slow the progression of Alzheimer's disease, and improve other neurodegenerative diseases [19]. ...
... This diet has gained popularity due to its favorable cardiovascular benefits, including rapid weight loss, decrease in serum hemoglobin A1c, and decrease in total cholesterol [19][20]. This diet has also been shown to be beneficial for patients on polydrug therapy for seizure disorders, slow the progression of Alzheimer's disease, and improve other neurodegenerative diseases [19]. Although all long-term effects are not well-established, this diet is controversial for its potential adverse effects, including dyslipidemia, glucose homeostasis, and liver steatosis [21]. ...
... However, in patients that present with hypokalemia, treating DKA with insulin can result in profound, symptomatic hypokalemia (<2.5) affecting neuromuscular and cardiopulmonary systems. Severe symptoms can range from muscular necrosis, ascending paralysis, cardiac arrhythmias, respiratory arrest, etc. [12,[19][20]38]. Therefore, the American Diabetes Association guidelines on DKA recommend checking and correcting any hypokalemia before starting IV insulin. ...
Article
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce cardiovascular, kidney, and overall mortality. SGLT2i are also associated with a rare adverse event, euglycemic diabetic ketoacidosis (EDKA). This report describes a case of EDKA one day after bariatric surgery in a 51-year-old female with type 2 diabetes mellitus managed with the SGLT2i, canagliflozin. She was following a ketogenic diet for three weeks prior to surgery. The patient made a steady recovery with rapid anion gap closure followed by prolonged non-anion gap metabolic acidosis. Her medical record was tagged with a life-threatening reaction to SGLT2i. The risk of EDKA from SGLT2i may be increased by a low carbohydrate diet or postoperative status. Our case was complicated by hypokalemia, exemplifying the need for aggressive electrolyte management. Further guidance is needed to manage risk factors provoking EDKA and the use of SGLT2i therapy after an episode of EDKA.
... Prior studies in both rats and humans reported a positive correlation between blood BHB and BDNF concentrations, suggesting that ketogenic interventions may improve cognition in part through a BDNF-mediated mechanism [10,11]. Although human studies are limited, this effect appears largely dependent on circulating BHB concentrations [12][13][14]. Besides the KD, circulating ketones can also be increased through exogenous ketone supplementation, which raise BHB rapidly after ingestion [15,16]. ...
... Considering a decrease in BDNF concentration is a cardinal feature of cognitive decline and the known effect of BHB to stimulate BDNF expression, relatively little research has been done exploring how ketogenic interventions influence plasma BDNF in humans. Both exogenous ketone esters and chronic KD consumption have been shown to increase BDNF [12,13], but no studies have examined the effects of ketone salt formulations or the impact of combined KD and exogenous ketone interventions. Moreover, there is little known on the impact of exercise and training status on the association between ketones and BDNF. ...
... It is possible that a higher BHB level, achievable for example with higher dose ketone esters, could create a significant change in BDNF after acute anaerobic exercise as it has been published that salts elicit a smaller BHB response than ketone esters [16,33]. Two previous studies found an increase in BDNF after adaptation of ketosis (by both KD and acute KE ingestion), but one trial where participants were fed a mixed diet with daily ingestion of 12 g of KE thrice daily found no difference in BDNF concentrations after the 14 day dietary intervention [12][13][14]. ...
Article
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Brain-Derived Neurotropic Factor (BDNF) expression is decreased in conditions associated with cognitive decline as well as metabolic diseases. One potential strategy to improve metabolic health and elevate BDNF is by increasing circulating ketones. Beta-Hydroxybutyrate (BHB) stimulates BDNF expression, but the association of circulating BHB and plasma BDNF in humans has not been widely studied. Here, we present results from three studies that evaluated how various methods of inducing ketosis influenced plasma BDNF in humans. Study 1 determined BDNF responses to a single bout of high-intensity cycling after ingestion of a dose of ketone salts in a group of healthy adults who were habitually consuming either a mixed diet or a ketogenic diet. Study 2 compared how a ketogenic diet versus a mixed diet impacts BDNF levels during a 12-week resistance training program in healthy adults. Study 3 examined the effects of a controlled hypocaloric ketogenic diet, with and without daily use of a ketone-salt, on BDNF levels in overweight/obese adults. We found that (1) fasting plasma BDNF concentrations were lower in keto-adapted versus non keto-adapted individuals, (2) intense cycling exercise was a strong stimulus to rapidly increase plasma BDNF independent of ketosis, and (3) clinically significant weight loss was a strong stimulus to decrease fasting plasma BDNF independent of diet composition or level of ketosis. These results highlight the plasticity of plasma BDNF in response to lifestyle factors but does not support a strong association with temporally matched BHB concentrations.
... Of the sixty-four publications reporting neurological outcomes (Table 2), twenty-two provided measures on cortical excitability (nineteen epilepsy studies (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) , one narcolepsy (40) , one glucose transporter-1 deficiency syndrome (41) and one general physiology (42) ). Additional categories included fifteen psychological publications (eleven mood and/or cognition (43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55) , one schizophrenia (56) and one orexinergic system (57) ), twelve neurodegenerative disease publications (three Alzheimer's disease (58)(59)(60) , three multiple sclerosis (61)(62)(63) , three cognitive impairment (64)(65)(66) and three Parkinson's disease (67)(68)(69) ), seven migraine publications (70)(71)(72)(73)(74)(75)(76) , two musculoskeletal studies (one hip osteoarthritis/pain (77) and one knee osteoarthritis/pain (78) ), two autonomic nervous system studies (one sympathetic activation (79) and one heart rate variability (80) ), two nervous system bioenergetics papers (one cerebral glucose uptake (81) and one cerebral blood flow (82) ), one spinal cord injury paper (83) and one traumatic brain injury paper (84) . Half of the included studies were randomised controlled trials (RCT) (n = 32), thirty were prospective single or two-arm studies, and two were case series (41,70) . ...
... Energy intake varied between studies; most reported ad libitum food intake or intake formulated for weight maintenance (n = 43), eight had mild-to-moderate calorie restriction (27,37,43,44,47,68,79,81) , six were very low-calorie (<800 kcal per day) (52,53,57,72,76,77) , three had combined protocols (51,71,73) and did not specify energy intake (56,67,70) . Weight loss prepost intervention was common (n = 45), but not always significant. ...
... These were mostly metabolic studies (n = 52) investigating chronic lifestyle diseases such as diabetes, obesity and heart disease (57, . The remaining studies included three general population (51,136,137) , two cancer (138,139) , two neurodegenerative disease (61,62) , one auto-immune (140) , one musculoskeletal (78) , one sport/performance (141) and one spinal cord injury (83) . There was a large proportion of RCTs (n = 45), seventeen prospective studies and one case series (138) . ...
Article
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Dietary restriction of carbohydrate has been demonstrated to be beneficial for nervous system dysfunction in animal models and may be beneficial for human chronic pain. The purpose of this review is to assess the impact of a low-carbohydrate/ketogenic diet on the adult nervous system function and inflammatory biomarkers to inform nutritional research for chronic pain. An electronic data base search was carried out in May 2021. Publications were screened for prospective research with dietary carbohydrate intake <130g/day and duration of ≥2 weeks. Studies were categorised into those reporting adult neurological outcomes to be extracted for analysis and those reporting other adult research outcomes Both groups were screened again for reported inflammatory biomarkers. From 1548 studies there were 847 studies included. Sixty-four reported neurological outcomes with 83% showing improvement. Five hundred and twenty-three studies had a different research focus (metabolic n=394, sport/performance n=51, cancer n=33, general n=30, neurological with non-neuro outcomes n=12, or gastrointestinal n=4). The second screen identified 63 studies reporting on inflammatory biomarkers with 71% reporting a reduction in inflammation. The overall results suggest a favourable outcome on the nervous system and inflammatory biomarkers from a reduction in dietary carbohydrates. Both nervous system sensitisation and inflammation occur in chronic pain and the results from this review indicate it may be improved by low-carbohydrate nutritional therapy. More clinical trials within this population are required to build on the few human trials that have been done.
... BDNF is one of the most wellstudied neurotrophins and is essential for brain function (Lima Giacobbo et al., 2019). Previous exploratory studies in human adults have found some associations between BHB and serum BDNF within a ketogenic diet intervention (Mohorko et al., 2019), and between BHB and plasma BDNF in the context of exogenous ketone ingestion (Walsh et al., 2020). Whether intake of kMCT, and subsequent ketosis, is associated with altered BDNF levels has to our knowledge not been studied. ...
... The positive association between BHB and mBDNF at baseline calls for replication in wider BHB ranges and is interesting in the light of reported associations between BDNF and memory performance in older adults (Shimada et al., 2014;Mizoguchi et al., 2020), as well as in other populations and neurological or psychiatric conditions (Lima Giacobbo et al., 2019). Increased mBDNF has further been reported after two weeks on a ketogenic diet, subsequently returning to baseline levels (Mohorko et al., 2019). Improved BDNF function could potentially constitute one mechanism by which ketogenic strategies, e.g., carbohydrate restriction, time-restricted feeding and ketogenic supplements, could affect brain health. ...
Article
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Background: β-hydroxybutyrate (BHB) can upregulate brain-derived neurotrophic factor (BDNF) in mice, but little is known about the associations between BHB and BDNF in humans. The primary aim here was to investigate whether ketosis (i.e., raised BHB levels), induced by a ketogenic supplement, influences serum levels of mature BDNF (mBDNF) and its precursor proBDNF in healthy older adults. A secondary aim was to determine the intra-individual stability (repeatability) of those biomarkers, measured as intra-class correlation coefficients (ICC). Method: Three of the arms in a 6-arm randomized cross-over trial were used for the current sub-study. Fifteen healthy volunteers, 65–75 y, 53% women, were tested once a week. Test oils, mixed in coffee and cream, were ingested after a 12-h fast. Labeled by their level of ketosis, the arms provided: sunflower oil (lowK); coconut oil (midK); caprylic acid + coconut oil (highK). Repeated blood samples were collected for 4 h after ingestion. Serum BDNF levels were analyzed for changes from baseline to 1, 2 and 4 h to compare the arms. Individual associations between BHB and BDNF were analyzed cross-sectionally and for a delayed response (changes in BHB 0–2 h to changes in BDNF at 0–4 h). ICC estimates were calculated from baseline levels from the three study days. Results: proBDNF increased more in highK vs. lowK between 0 and 4 h (z-score: β = 0.25, 95% CI 0.07–0.44; p = 0.007). Individual change in BHB 0–2 h, predicted change in proBDNF 0–4 h, (β = 0.40, CI 0.12–0.67; p = 0.006). Change in mBDNF was lower in highK vs. lowK at 0–2 h (β = −0.88, CI −1.37 to −0.40; p < 0.001) and cumulatively 0–4 h (β = −1.01, CI −1.75 to −0.27; p = 0.01), but this could not be predicted by BHB levels. ICC was 0.96 (95% CI 0.92–0.99) for proBDNF, and 0.72 (CI 0.47–0.89) for mBDNF. Conclusions: The findings support a link between changes in peripheral BHB and proBDNF in healthy older adults. For mBDNF, changes differed between arms but independent to BHB levels. Replication is warranted due to the small sample. Excellent repeatability encourages future investigations on proBDNF as a predictor of brain health. Clinical Trial Registration: ClinicalTrials.gov , NCT03904433.
... The reduction of carbohydrate intake naturally reduces blood glucose levels, thus reducing insulin as a result. Many studies have now demonstrated that the ketogenic diet reduces both blood glucose and insulin levels [55][56][57] A study conducted by Fumagalli et al. [58] analyzed the genetic profiles of patients and looked at the impacts on metabolism. They specifically looked at human CHC22 clathrin, which plays a central role in intracellular traffic of insulin-responsive glucose transporter 4 (GLUT4). ...
... Studies that include this measurement can therefore confirm dietary adherence and determine the true effects of the diet on health outcomes, like weight loss. Mohorko et al. [57] conducted a 12-week ketogenic diet study on obese patients who were calorie restricted (1200-1500kcal) for the first two weeks and then were instructed to eat ad-libitum for hunger for the remaining weeks while eating the macronutrient composition necessary to remain in a state of nutritional ketosis. BHB was measured throughout the study and patients maintained levels above 0.5 mmol throughout the 12 weeks. ...
Article
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Considering the lack of a comprehensive, multi-faceted overview of the ketogenic diet (KD) in relation to health issues, we compiled the evidence related to the use of the ketogenic diet in relation to its impact on the microbiome, the epigenome, diabetes, weight loss, cardiovascular health, and cancer. The KD diet could potentially increase genetic diversity of the microbiome and increase the ratio of Bacteroidetes to Firmicutes. The epigenome might be positively affected by the KD since it creates a signaling molecule known as β-hydroxybutyrate (BHB). KD has helped patients with diabetes reduce their HbA1c and reduce the need for insulin. There is evidence to suggest that a KD can help with weight loss, visceral adiposity, and appetite control. The evidence also suggests that eating a high-fat diet improves lipid profiles by lowering low-density lipoprotein (LDL), increasing high-density lipoprotein (HDL), and lowering triglycerides (TG). Due to the Warburg effect, the KD is used as an adjuvant treatment to starve cancer cells, making them more vulnerable to chemotherapy and radiation. The potential positive impacts of a KD on each of these areas warrant further analysis, improved studies, and well-designed randomized controlled trials to further illuminate the therapeutic possibilities provided by this dietary intervention.
... Although there is some indication that KD may suppress ghrelin levels (see review by Roekenes and Martins (107)), there are some inconsistencies in the literature (108)(109)(110)(111). Leptin and peptide YY have effects opposite to ghrelin, in that they promote satiety (112,113). A KD has been shown to increase serum peptide YY levels (114), though it has also been shown to decrease leptin levels (115,116). ...
... Mechanistically, D-BHB enhances the expression of BDNF through downstream targeting of CREB and acetylation of BDNF promoters (176)(177)(178). While some clinical evidence points to serum BDNF being significantly increased following adherence to a KD (116,179,180), Vizuete et al. (181) found a KD decreased striatal BDNF levels and had no effect on hippocampal levels of BDNF in Wistar rats. The KD and D-BHB's effect on BDNF expression in the context of AUD warrants investigation. ...
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Alcohol use disorder (AUD) is a chronic, relapsing brain disorder, characterized by compulsive alcohol seeking and disrupted brain function. In individuals with AUD, abstinence from alcohol often precipitates withdrawal symptoms than can be life threatening. Here, we review evidence for nutritional ketosis as a potential means to reduce withdrawal and alcohol craving. We also review the underlying mechanisms of action of ketosis. Several findings suggest that during alcohol intoxication there is a shift from glucose to acetate metabolism that is enhanced in individuals with AUD. During withdrawal, there is a decline in acetate levels that can result in an energy deficit and could contribute to neurotoxicity. A ketogenic diet or ingestion of a ketone ester elevates ketone bodies (acetoacetate, β-hydroxybutyrate and acetone) in plasma and brain, resulting in nutritional ketosis. These effects have been shown to reduce alcohol withdrawal symptoms, alcohol craving, and alcohol consumption in both preclinical and clinical studies. Thus, nutritional ketosis may represent a unique treatment option for AUD: namely, a nutritional intervention that could be used alone or to augment the effects of medications.
... Notably, two recent reports suggested positive effects of LCDs on eating behavior. One uncontrolled intervention study demonstrated that a 12-week LC resulted in decreased emotional and external eating in obese adults (20), and dietary restraint was also increased significantly according to the report from another non-randomized controlled study (21). However, more studies with larger sample sizes and randomized controlled designs are needed to support the beneficial effects of LCDs on eating behaviors. ...
... Despite the correlation between anxiety levels and emotional eating scores, no statistical changes were found in any subscale of eating behaviors in the LC-CON and LC-EXE groups. Conversely, significantly increased dietary restraint was reported in a 4-week study, and decreased emotional and external eating were observed in another 12-week study (20,21). It is unknown whether differences in food cravings or food preference account for the inconsistent findings in eating behaviors, as participants with high levels of cravings for high-fat food at baseline might be satisfied with the LCD. ...
Article
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Background The effectiveness of low-carbohydrate diets (LCDs) on weight loss and exercise for improving cardiometabolic fitness have been well documented in the literature, but the effects of LCDs and whether adding exercise to a LCD regime could additionally benefit mental health (e. g., by lowering the level of anxiety) and associated changes in eating behavior are less clear in overweight and obese populations. Therefore, this study aimed to investigate the effects of a 4-week LCD with or without exercise on anxiety and eating behavior, and to explore the associations between changes in the psychological state and physiological parameters (i.e., body composition, aerobic fitness, blood pressure, lipid profile, and metabolic hormones).Methods Seventy-four overweight Chinese women [age: 20.8 ± 3.0 years, body mass index (BMI): 25.3 ± 3.3 kg·m−2] completed the 4-week randomized controlled trial, which included a LCD group (i.e., ~50 g daily carbohydrate intake) with exercise training 5 days/week (LC-EXE, n = 26), a LCD group without exercise training (LC-CON, n = 25) and a control group that did not modify their habitual diets and physical activity (CON, n = 23). Levels of anxiety, eating behavior scores and physiological parameters (i.e., body weight, V̇O2peak, blood pressure, fasting glucose, blood lipids, and serum metabolic hormones including insulin, C-peptide, leptin, and ghrelin) were measured before and after the intervention.ResultsThere were significant reductions in anxiety levels in the LC-EXE compared with the LC-CON group, while no statistical changes were found in eating behaviors in any conditions after the 4-week intervention. Significant reduction in weight (~3.0 kg or 4%, p < 0.01) and decreases in insulin (~30% p < 0.01), C-peptide (~20% p < 0.01), and leptin (~40%, p < 0.01) were found in both LC-CON and LC-EXE groups, but adding exercise to a LCD regime generated no additional effects. There were significant improvements in V̇O2peak (~15% p < 0.01) and anxiety (~25% p < 0.01) in the LC-EXE compared with the LC-CON group, while no statistical differences were found between CON and LC-CON treatments. Further analysis revealed a negative association (r = −0.32, p < 0.01) between changes in levels of anxiety and changes in V̇O2peak in all participates, no other correlations were found between changes in psychological and physiological parameters.Conclusion Although the combination of a LCD and exercise may not induce additional reductions in body weight in overweight young females, exercise could be a useful add-on treatment along with a LCD to improve cardiometabolic health and lower anxiety levels.
... A keto diet is a strict low-carbohydrate and high-fat diet. It has recently been very famous in the United States and globally due to its fast weight loss benefits [1,2]. The reduction in carbohydrates enables the body to rely on fat as a predominant energy source leading to a state of ketosis. ...
... The aim of this diet is to enter a state of nutritional ketosis, deriving energy from fat burn-down, in the form of ketones. Short-term benefits have been postulated by faster weight loss, improved cognitive functioning, appetite suppression, and improved eating behaviour and metabolic profile [2]. However, the long-term benefits have been largely unexplored [5]. ...
Article
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Diabetic ketoacidosis (DKA) is one of the serious complications of diabetes, especially type 1. It is defined by the triad of hyperglycemia (>250 mg/dL [>13.9 mmol/L]), high anion-gap metabolic acidosis, and increased plasma ketones. Euglycemic ketoacidosis is characterized by DKA without hyperglycemia. We present a rare case of a 28-year-old type 1 diabetic male, presenting with abdominal pain, fatigue, and dizziness after one week of starting a keto diet. He was diagnosed with euglycemic DKA, managed with DKA protocol and given detailed dietary counselling to avoid the keto diet in future.
... the key" and it should be used with caution for long term to avoid nutritional deficiencies [6][7][8][9][10][11][12]. ...
Article
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Ketogenic diet is a high fat, moderate protein, low carbohydrate diet in which energy source is ketones instead of glucose, which was initially designed to treat epilepsy but it proved in delivering many other health benefits including weight loss, fat loss, improves glucose and insulin levels, sometimes it results in skin glow and many others health benefits. Intake of ketogenic diet will place your body into a state of “ketosis”. A process when human body becomes a fat burner rather than sugar burner. The present study includes brief description about ketogenic diet and its types, history, biochemistry, its benefits and their side-effects.
... There are six recent studies concerning KD different from that of VLCKD, out of which four used no control group for comparison (Hall et al., 2016;Kenig, Petelin, Poklar Vatovec, Mohorko, & Jenko--Pražnikar, 2019;Mohorko et al., 2019;Schiavo et al., 2018). In the study with seventeen men, four week KD with calorie intake approx. ...
Article
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Background In recent times, the prevalence of obesity increases, reaching an epidemic scale. Elevated body weight is a risk factor in the development of several diseases such as diabetes, hypertension and cancer. Therefore, obesity management solutions, such as diet therapy, are needed. The key issue is to choose the most appropriate diet to obtain an efficient outcome of losing weight, without experiencing adverse effects and a decrease in general health. A ketogenic diet (KD), an auxiliary therapy for epilepsy, is one of the options recently suggested for losing weight. Scope and approach In this review, the current knowledge about the KD and its application in obesity management are discussed. Moreover, the difficulties encountered in clinical studies with KD intervention are addressed. Finally, the future studies needed to understand the physiological effect of the KD on the human body are underlined. Key findings and conclusions The results of recently published clinical trials indicated that KD can be efficient for losing weight and changing body composition without causing severe adverse effects. However, many studies were conducted with a very-low-calorie regime, which itself may affect the loss of body weight, and in many studies to date, the control diets were missing. To summarize, to be able to recommend a KD for weight management, a more in-depth elucidation of the safety and physiological effects of KD in obese individuals is needed.
... ( McClernon et al., 2007). Similarly, participants in an uncontrolled intervention study had experienced a decrease in insulin levels, BMI, and cognitive functions after 12 weeks (Mohorko et al., 2019). Improvements in metabolic pro le with KD have also been characterized by decreasing levels of triglycerides and low-density lipoprotein cholesterol (LDL) and increasing levels of high-density lipoprotein (HDL) cholesterol (Dashti et al., 2006;Yancy et al., 2004). ...
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Background: Bipolar disorder is a neurodevelopmental illness characterized by severe biphasic changes in mood, energy, or thought. Key underlying metabolic pathologies thought to play a role include dysfunction in energy metabolism. The purpose of this article is to review the findings to date of the effects of a low carbohydrate ketogenic diet (KD) on mood symptoms in preclinical and clinical models of bipolar illness. The review highlights the underlying metabolic pathologies of bipolar disorder (BD) and potential therapeutic effects of the KD on these pathologies. The article also explores the potential effects of a KD on metabolic health in BD, including proposed mechanisms of action. Summary: Recent findings support the idea that bipolar disorder, along with other psychiatric disease, may have roots of metabolic dysfunction: cerebral glucose hypometabolism, oxidative stress, as well as mitochondrial and neurotransmitter dysfunction which has downstream effects on synapse connections. A KD provides alternative fuel to the brain aside from glucose and is believed to contain beneficial neuroprotective effects, including stabilization of brain networks, reduction of inflammation and oxidative stress. Several beneficial metabolic effects on insulin resistance, weight, and lipids have been shown. Based on its effectiveness in treating epilepsy, the KD has garnered recent interest in its application for mood disorders as it may imitate the pharmacological effects of mood stabilizers, commonly prescribed agents in the treatment of both BD and epilepsy. Additionally, it may improve metabolic dysfunction often seen in BD and repair deficits in energy metabolism. Limited case studies on KD treatment in BD have been reported; however, studies addressing the potential therapeutic effects of KD on metabolic abnormalities in mental illness are promising. Literature of plausible mechanisms and reports of improvements in psychosis, cognition and mood symptoms have been increasing. Conclusions: Preliminary findings support further testing of a low carbohydrate KD as a potential therapeutic tool in repairing energy metabolism in bipolar illness. Further research and clinical trials are needed to evaluate the efficacy of a KD as a supplemental or co-treatment of bipolar illness and the first open-label trial testing the diet in bipolar illness is currently underway at Stanford.
... Some research has revealed that during weight loss programs subjects may experience depression and negative feelings [28]. However, in humans, KD has been shown to raise BDNF levels, probably via BHB regulation [82], which was also associated with substantial improvement in cognitive function [83]. BHB regulates BDNF expression in the mouse brain by a mechanism similar to the one induced by exercise. ...
Article
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Background: Ketogenic diet (KD) is a nutritional approach that restricts daily carbohydrates, replacing most of the reduced energy with fat, while maintaining an adequate quantity of protein. Despite the widespread use of KD in weight loss in athletes, there are still many concerns about its use in sports requiring muscle mass accrual. Thus, the present study sought to investigate the influence of a KD in competitive natural body builders. Methods: Nineteen volunteers (27.4 ± 10.5 years) were randomly assigned to ketogenic diet (KD) or to a western diet (WD). Body composition, muscle strength and basal metabolic rate were measured before and after two months of intervention. Standard blood biochemistry, testosterone, IGF-1, brain-derived neurotrophic factor (BDNF) and inflammatory cytokines (IL6, IL1β, TNFα) were also measured. Results: Body fat significantly decreased in KD (p = 0.030); whilst lean mass increased significantly only in WD (p < 0.001). Maximal strength increased similarly in both groups. KD showed a significant decrease of blood triglycerides (p < 0.001), glucose (p = 0.001), insulin (p < 0.001) and inflammatory cytokines compared to WD whilst BDNF increased in both groups with significant greater changes in KD (p < 0.001). Conclusions: KD may be used during body building preparation for health and leaning purposes but with the caution that hypertrophic muscle response could be blunted.
... (McClernon et al., 2007). Similarly, participants in an uncontrolled intervention study had experienced a decrease in insulin levels, BMI, and cognitive functions after 12 weeks (Mohorko et al., 2019). Improvements in metabolic pro le with KD have also been characterized by decreasing levels of triglycerides and low-density lipoprotein cholesterol (LDL) and increasing levels of high-density lipoprotein (HDL) cholesterol (Dashti et al., 2006;Yancy et al., 2004). ...
Preprint
Full-text available
Background: Bipolar disorder is a neurodevelopmental illness characterized by severe biphasic changes in mood, energy, or thought. Key underlying metabolic pathologies thought to play a role include dysfunction in energy metabolism. The purpose of this article is to review the findings to date of the effects of a low carbohydrate ketogenic diet (KD) on mood symptoms in preclinical and clinical models of bipolar illness. The review highlights the underlying metabolic pathologies of bipolar disorder (BD) and potential therapeutic effects of the KD on these pathologies. The article also explores the potential effects of a KD on metabolic health in BD, including proposed mechanisms of action. Summary: Recent findings support the idea that bipolar disorder, along with other psychiatric disease, may have roots of metabolic dysfunction: cerebral glucose hypometabolism, oxidative stress, as well as mitochondrial and neurotransmitter dysfunction which has downstream effects on synapse connections. A KD provides alternative fuel to the brain aside from glucose and is believed to contain beneficial neuroprotective effects, including stabilization of brain networks, reduction of inflammation and oxidative stress. Several beneficial metabolic effects on insulin resistance, weight, and lipids have been shown. Based on its effectiveness in treating epilepsy, the KD has garnered recent interest in its application for mood disorders as it may imitate the pharmacological effects of mood stabilizers, commonly prescribed agents in the treatment of both BD and epilepsy. Additionally, it may improve metabolic dysfunction often seen in BD and repair deficits in energy metabolism. Limited case studies on KD treatment in BD have been reported; however, studies addressing the potential therapeutic effects of KD on metabolic abnormalities in mental illness are promising. Literature of plausible mechanisms and reports of improvements in psychosis, cognition and mood symptoms have been increasing. Conclusions: Preliminary findings support further testing of a low carbohydrate KD as a potential therapeutic tool in repairing energy metabolism in bipolar illness. Further research and clinical trials are needed to evaluate the efficacy of a KD as a supplemental or co-treatment of bipolar illness and the first open-label trial testing the diet in bipolar illness is currently underway at Stanford.
... It has been consistently shown by our research group [3 & ,5,6,12] and others [2] that under ketogenic conditions, feelings of hunger, measured using validated visual analogue scales (VASs), do not increase, even when massive weight loss is achieved (up to 17% or initial body weight) [13]. Studies where hunger feelings have been evaluated through other methods, such as the Three Factor Eating Questionnaire [14], the Food Craving Questionnaire [15], nonvalidated questionnaires [16,17,18], semi-structured interviews, [19] and case reports [20,21] have also confirmed that ketogenic diets are associated with diminished or absent feelings of hunger, a reduced desire to eat and decreased overall appetite. ...
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Purpose of review: The popularity of ketogenic diets in the treatment of obesity has increased dramatically over the last years, namely due to their potential appetite suppressant effect. The purpose of this review was to examine the latest evidence regarding the impact of ketogenic diets on appetite. Recent findings: The majority of the studies published over the last 2 years adds to previous evidence and shows that ketogenic diets suppress the increase in the secretion of the hunger hormone ghrelin and in feelings of hunger, otherwise see when weight loss is induced by non-ketogenic diets. Research done using exogenous ketones point out in the same direction. Even though the exact mechanisms by which ketogenic diets suppress appetite remain to be fully determined, studies show that the more ketotic participants are (measured as β-hydroxybutyrate plasma concentration), the smaller is the increase in ghrelin and hunger and the larger is the increase in the release of satiety peptides. Further evidence for a direct effect of ketones on appetite comes from studies using exogenous ketones. Summary: The appetite suppressant effect of ketogenic diets may be an important asset for improving adherence to energy restricted diets and weight loss outcomes.
... Stable fasting blood ketones have been observed at weeks two, three and four of an isocaloric ketogenic diet in a previous inpatient controlled feeding study, 24 suggesting that it is unlikely that further increases in ketones would be expected with prolonged exposure to the LC diet. Finally, plasma uric acid approximately doubles at the onset of a ketogenic diet but returns to ~20-50% greater than baseline after 4-8 weeks of adaptation in an outpatient setting [25][26][27] . This was similar to the ~35% greater than baseline uric acid levels that we observed after 2 weeks of inpatient LC feeding ( Table 2) and suggests that outpatient studies may require longer adaptation periods to ketogenic diets, perhaps due to reduced diet adherence compared to our inpatient study that had greater control over the food environment. ...
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The carbohydrate–insulin model of obesity posits that high-carbohydrate diets lead to excess insulin secretion, thereby promoting fat accumulation and increasing energy intake. Thus, low-carbohydrate diets are predicted to reduce ad libitum energy intake as compared to low-fat, high-carbohydrate diets. To test this hypothesis, 20 adults aged 29.9 ± 1.4 (mean ± s.e.m.) years with body mass index of 27.8 ± 1.3 kg m⁻² were admitted as inpatients to the National Institutes of Health Clinical Center and randomized to consume ad libitum either a minimally processed, plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with high glycemic load (85 g 1,000 kcal⁻¹) or a minimally processed, animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with low glycemic load (6 g 1,000 kcal⁻¹) for 2 weeks followed immediately by the alternate diet for 2 weeks. One participant withdrew due to hypoglycemia during the low-carbohydrate diet. The primary outcomes compared mean daily ad libitum energy intake between each 2-week diet period as well as between the final week of each diet. We found that the low-fat diet led to 689 ± 73 kcal d⁻¹ less energy intake than the low-carbohydrate diet over 2 weeks (P < 0.0001) and 544 ± 68 kcal d⁻¹ less over the final week (P < 0.0001). Therefore, the predictions of the carbohydrate–insulin model were inconsistent with our observations. This study was registered on ClinicalTrials.gov as NCT03878108.
... Prospective cohort study conducted in USA on 15,428 adults aged 45-64 years and a meta-analysis of 8 cohort studies showed low carbohydrate intake (<40% total energy) and high carbohydrate (> 70% total energy) had a higher risk of death compared 1. Weight loss (Mohorko et al. 2019;Gomez-Arbelaez et al. 2017;Mansoor et al. 2016) Weight loss is signifi cantly higher than other diets, especially in subjects that are obese and overweight. ...
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The prevalence of obesity has increased signifi cantly and it has become a public health problem globally. Many strategies were done to overcome obesity. One of them is dietary approach. The popular and widely used weight loss diet is the ketogenic diet. This literature review aimed to discuss the mechanism of ketogenic diet in weight lost as well as its long and short term eff ects on health. Ketogenic diet is a very low-carbohydrate and high-fat diet. This diet restricts the carbohydrate intake up to 50 gram per day. The diet eff ective for losing weight in short term (<6 months), after 6 months there was no signifi cant diff erences compared to other wight-loss diet. Study shows ketogenic diet gives both benefi cial and harmful eff ects in short and long term for ketogenic dieters. This diet is not applicable for anyone, thus people with chronic diseases should receive guidance from dietitian or clinician in implementing this diet. Ketogenic dieters are suggested to replace their carbohydrate intake with complex carbohydrate (whole food-not refi ned), reduce animal-based protein, increasing plant-based protein and polyunsaturated fat, water, fermented foods and beverages.
... The community contains themes related to the so-called Ketogenic diets, such as low carb, keto recipes, keto lifestyle, keto weight loss, keto meals, etc. Ketogenic diet is a low-carbohydrate diet with high fat content, which results in the production of ketones by the liver and their uptake as an alternative energy source by the brain [137][138][139]. Although this dietary approach was previously used mainly to treat intractable epilepsy [140], it is currently being promoted as a strategy to combat obesity [141]. ...
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Social media platforms have become part of many people’s lives. Users are spending more and more time on these platforms, creating an active and passive digital footprint through their interaction. This footprint has high research potential in many research areas because understanding people’s communication on social media is essential in understanding their values, attitudes, experiences and behaviors. Researchers found that the use of social networking sites impacts adolescents’ eating behavior. If we define adolescents as individuals between ages 10 and 24 (WHO’s definition), 76% of USA young people at age 18–⁠24 use Instagram, so the Instagram social network analysis is important for understanding young people’s expressions in the context of healthy food. This study aims to identify the main topic associated with healthy food on the Instagram social network via hashtag and community analysis based on 2,045,653 messages created by 427,936 individual users. The results show that users most associate Healthy food with healthy lifestyle, fitness, weight loss and diet. In terms of food, these are foods that are Vegan, Homemade, Clean and Plant-based. Given that young people change their behavior in relation to people’s behavior on social networks, it is possible to use this data to predict their future association with healthy food characteristics.
... In the group including physical activity and the dietary intervention, the improvement in binge eating behaviors was not significant, although emotional eating and uncontrolled eating were improved [44]. In another study, Mohorko et al. demonstrated that a 12-week ketogenic diet, leading to a significant reduction in caloric intake, decreased emotional and external eating and improved cognitive function, but these results need to be confirmed in a randomized controlled trial [50]. ...
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Purpose of Review Restrictive diets, such as low-calorie diets, are difficult to maintain in the long term. For this reason, their popularity has decreased compared to non-restrictive approaches, which instead promote healthy eating strategies. Since both strategies may entail different neurobiological mechanisms, this review will examine the current evidence on the effects of restrictive and non-restrictive interventions on neurobehavioral factors. Recent Findings Restrictive diets appear to improve eating behaviors, and the evidence reviewed argues against the notion that they may worsen the severity of binge eating. Moreover, they may lead to short-term changes in brain structure and improvements in cerebrovascular markers which, in turn, could impact eating behaviors. Non-restrictive interventions may have a positive effect on weight management and eating behaviors. However, evidence of their neural effects is scarce. Summary Small sample sizes, short follow-ups, and the absence of control groups are limitations of the studies targeting both interventions. Rigorous long-term randomized studies are needed to examine the neurobehavioral effects of restrictive and non-restrictive approaches.
... 25,26 Likewise, BMIs at post-intervention and follow-up were significantly lower than at baseline, a finding consistent with previous studies. 27,28 Pairwise comparisons of the three groups revealed that the MHE group had the highest average scores for perceived benefits, barriers, and self-efficacy in dietary life. The FHE group showed the highest score in perceived threat, cues to action, and self-efficacy in exercise. ...
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Background : Obesity is considered a significant public health problem in Thailand. This study was conducted to compare the impact of mobile health education messages verses face-to-face consultation on weight reduction among overweight female university students. Methods : This comparative cross-sectional study comprised three groups: a control group, a group receiving mobile health education, and a group receiving face-to-face consultation. Each group contained 26 participants taking part over a period of 12 weeks, with a 12-week follow-up thereafter. The data analysis used two-way repeated measures ANOVA with least significant difference testing. The study was ethically approved at Chulalongkorn University, Thailand. Results : The results revealed that the group receiving mobile health education had the lowest average body mass index and waist–hip ratio after intervention ( p < 0.05). In addition, both intervention groups significantly improved their health belief, social support, and health behavior scores in comparison to the control group ( p < 0.001). The results show that the average scores for social support for eating and exercise at baseline were significantly lower than at post-intervention or follow-up ( p < 0.001). In addition, the results of both aspects of social support showed that the average social support score at post-intervention was significantly higher than at follow-up. Furthermore, the health behavior score measured post-intervention was higher than at follow-up. There was a statistically significant difference in average metabolism during physical activity ( p < 0.001) but no statistical difference in average eating behavior score. Conclusion : The study found that the use of mobile health education to deliver health programs facilitates communication between the healthcare provider and individual, and can empower adolescent females in their pursuit of weight loss by improving their attitudes and knowledge, leading to better health behavior.
... In the context of overweight/obesity and type 2 diabetes, a hypocaloric KD was superior to standard CR for weight loss and glycemic control (99,100). For weight loss in general, a lowfat diet or KD are equally effective given equal caloric intake; however, long-term compliance may be better with a KD due to its appetite-reducing effects (101)(102)(103)(104), which counteract the increase in appetite that accompanies weight loss (105,106). Thus, akin to IF/TRF, the KD presents advantages over conventional CR for weight loss and holds promise for addressing the intersection of ADPKD and obesity. ...
Article
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive growth of renal cysts, leading to the loss of functional nephrons. Recommendations for individuals with ADPKD to maintain a healthy diet and lifestyle are largely similar to those for the general population. However, recent evidence from preclinical models suggests that more tightly specified dietary regimens including caloric restriction, intermittent fasting, and ketogenic diets hold promise to slow disease progression, and the results of ongoing human clinical trials are eagerly awaited. These dietary interventions directly influence nutrient signalling and substrate availability in the cystic kidney, while also conferring systemic metabolic benefits. The present review focuses on the importance of local and systemic metabolism in ADPKD and summarizes current evidence for dietary interventions to slow disease progression and improve quality of life.
... W przypadku leczenia cukrzycy korzystne działanie KD związane jest z obniżoną podażą glukozy, a w konsekwencji z redukcją poziomu insuliny i obniżeniem stężenia glukozy we krwi. Istotna jest również towarzysząca stosowaniu KD redukcja masy ciała [24][25][26]. Stosowanie KD skutkuje również obniżeniem HbA1c i zmniejszeniem zapotrzebowania na insulinę [27][28][29]. Badanie C.C. Webstera i wsp. ...
... Some limitations of the present study have to be considered. First, we did not measure appetite-related hormones as previous ketogenic diet research did (13)(14)(15) or other molecules supposedly influenced by ketogenic diets and linked to cognitive performance, such as brain-derived neurotrophic factor (45). Moreover, the short duration of the study is a limitation, even though we precisely designed the study to understand the short-term effects of ketogenic diets on mood and cognitive functions. ...
Article
Objective: This study sought to investigate how glycemia and ketonemia variations during two ketogenic diet protocols affect appetite, executive functions, and mood in young women with overweight. Methods: Fifty healthy young females with overweight were randomly assigned to (1) a ketogenic diet without any restriction on energy intake, (2) a commercial energy-restricted ketogenic Mediterranean diet, and (3) an energy-restricted Mediterranean diet for 10 days. A visual analogue scale was used to test appetite, and one mood test and two cognitive tasks (working memory and inhibition control) were performed. Moreover, body composition, fasting blood glucose, and β-hydroxybutyrate (BHB) were measured. Results: A positive correlation was found between glycemia and appetite (P = 0.019), unfullness score (P = 0.001), and desire to eat (P = 0.030) (pre- and postdiet levels). Postdiet BHB levels showed a positive correlation with fullness score (P = 0.002) and a negative correlation with appetite (P = 0.022) and desire to eat (P = 0.009). A positive correlation was found between prediet levels of glycemia and reaction times in the go-trials of the executive function test (P = 0.018). Postdiet BHB level showed a negative correlation with the accuracy of the no-go trials (P = 0.027). Conclusions: Ketogenic diets, compared with a Mediterranean diet, have a greater effect in terms of appetite reduction but might affect inhibition functions.
... There are many ways to intervene obesity, including exercise, diets, drugs, and surgery. Previous studies have demonstrated that obesity-induced impairment of cognitive and memory function can be suppressed and rescued after exercise [4], ketogenic diet [5], and surgical interventions due to body weight loss [6]. Therefore, the gain of body weight may be the culprit. ...
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Obesity is an important public health problem nowadays. Long-term obesity can trigger a series of chronic diseases and impair the learning and memory function of the brain. Current studies show that scientific exercise can effectively improve learning and memory capacity, which also can provide benefits for obese people. However, the underlying mechanisms for the improvement of cognitive capacity under the status of obesity still need to be further explored. In the present study, the obesity-induced cognition-declined model was established using 4-week-old mice continuously fed with a high-fat diet (HFD) for 12 weeks, and then the model mice were subjected to an 8-week swimming intervention and corresponding evaluation of relevant indicators, including cognitive capacity, inflammation, insulin signal pathway, brain-derived neurotrophic factor (BNDF), and apoptosis, for exploring potential regulatory mechanisms. Compared with the mice fed with regular diets, the obese mice revealed the impairment of cognitive capacity; in contrast, swimming intervention ameliorated the decline in cognitive capacity of obese mice by reducing inflammatory factors, inhibiting the JNK/IRS-1/PI3K/Akt signal pathway, and activating the PGC-1α/BDNF signal pathway, thereby suppressing the apoptosis of neurons. Therefore, swimming may be an important interventional strategy to compensate for obesity-induced cognitive impairment.
... These results could be due to changes in body composition as well as psychological responses in participants with obesity. Exergaming led to a development of positive self-esteem, an improvement in physical performance and cognitive function and an enhancement of perceived physical values of participants with obesity (38). Several studies supported the positive effect of Ramadan fasting on psychological states and well-being (39,40). ...
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The effects of exergaming on biochemical responses has been investigated; however, no data is available for this effect during Ramadan intermittent fasting (RIF). RIF is a daily fasting characterized by abstaining from eating and drinking from sunrise to sunset for 29–30 days. The purpose of this study was to investigate the effect of exergaming during RIF on body composition, physical performance and hematological parameters in overweight and adolescents with obesity. Twenty-four adolescents with obesity were divided into two groups [control group (CG), n = 12, or cooperative sport exergaming group (EG), n = 12: 45 min per session during five days per week)]. Participants completed a 6-min walking test (6MWT), a squat jump test and a 10 and a 30m sprint tests in four different occasions: before Ramadan (T0), the second week of Ramadan (T1), the fourth week of Ramadan (T2), and after Ramadan (T3). Blood pressure, rating of perceived exertion (RPE), body composition, central obesity index, dietary intake and profile of mood states (POMS) were, also, assessed over the four periods. The results showed that body weight, body mass index and body fat percentage were significantly lower at T2 compared to T0 and T1 in the EG. After RIF, body composition returned to the values recorded before RIF. The POMS score was significantly lower during T2 compared to T0, T1 and T3 in the EG. The vertical jump and the 6MWT distance were significantly higher (i) at T2 compared to T0, T1 and T3 in the EG and (ii) in EG compared to CG at T2. RPE was significantly lower (i) at T2 compared to T0, T1 and T3 in the EG and (ii) in EG compared to CG at T2. Blood pressure was lower during T2 compared to the other periods in EG. The EG experienced significant decreases in total cholesterol and triglycerides during T2. However, no significant changes between groups and periods was reported for all the other parameters. In conclusion, exergaming during RIF has a positive effect on body composition and physiological and psychological responses in adolescents with obesity.
... It was identified that it takes approximately 4-6 weeks on the ketogenic diet before uric acid returns to normal levels. In some cases, however, the period before normal uric acid levels were noticed was 12 weeks [45]. This further suggests that the 3-week intervention [8]and possibly even the 5-and-a-half-week intervention [10] [18] did not allow sufficient time for the studies to provide substantial evidence. ...
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This paper reviews the literature in ketogenic diets and athletic performance. The review aims to compare, and contrast differing scientific opinions and gain a clearer understanding of the diet’s validity in athletic performance. The role of a low carbohydrate and high fat (LCHF) diet or ketogenic diet on athletic performance has created much debate in recent years. Evidence identifying that the diet fails to improve and rather diminishes performance has been discussed in literature, however advocates of the diet have found methodological flaws in research previously conducted. The purpose of this paper is to review literature surrounding the use of LCHF diets in sports performance and compare these reviews with previous literature on the efficacy of carbohydrates as a main fuel source. A total of 63 papers and scientific presentations were utilized for review. A large portion of research for the LCHF diets suggests an adaptation period lasting between 4 weeks to as high as 3 months is required before improvements start to be noticed. Studies follow a trend with improvements being more common over longer-term dietary interventions rather than short term investigations. Evidence continually shows improved fat oxidation on a LCHF; however, this phenomenon does not necessarily correlate with performance output with some investigations identifying reduced VO2max results. Alternatively, longer investigations have identified no difference between groups (i.e., no loss in performance) or in some cases an improved VO2max output. Results on power output have again showed interesting features with the diet being clearly advantageous for weight loss that is not associated with performance deterioration. Overall, the jury remains out over the effects of a diet of this nature, however there is room for collaboration between the low carbohydrate and high carbohydrate groups to create methodological sound studies that may shed more light on the actual benefits and detriments of such a diet.
... Adipokines serve as an important link between metabolic function, inflammation and the immune response. [17][18][19] The study of KDs in humans with MS is limited. While KDs may offer benefits to patients with MS, there are potential risks associated with the KD's strict nutritional parameters-including metabolic acidosis, nephrolithiasis, hyperlipidaemia and select nutrient deficiencies. ...
Article
Background Dietary changes impact human physiology and immune function and have potential as therapeutic strategies. Objective Assess the tolerability of a ketogenic diet (KD) in patients with relapsing multiple sclerosis (MS) and define the impact on laboratory and clinical outcome metrics. Methods Sixty-five subjects with relapsing MS enrolled into a 6-month prospective, intention-to-treat KD intervention. Adherence was monitored with daily urine ketone testing. At baseline, fatigue, depression and quality of life (QoL) scores were obtained in addition to fasting adipokines and MS-related clinical outcome metrics. Baseline metrics were repeated at 3 and/or 6 months on-diet. Results Eighty-three percent of participants adhered to the KD for the study duration. Subjects exhibited significant reductions in fat mass and showed a nearly 50% decline in self-reported fatigue and depression scores. MS QoL physical health (67±16 vs 79±12, p<0.001) and mental health (71±17 vs 82±11, p<0.001) composite scores increased on-diet. Significant improvements were noted in Expanded Disability Status Scale scores (2.3±0.9 vs 1.9±1.1, p<0.001), 6-minute walk (1631±302 vs 1733±330 ft, p<0.001) and Nine-Hole Peg Test (21.5±3.6 vs 20.3±3.7 s, p<0.001). Serum leptin was lower (25.5±15.7 vs 14.0±11.7 ng/mL, p<0.001) and adiponectin was higher (11.4±7.8 vs 13.5±8.4 µg/mL, p=0.002) on the KD. Conclusion KDs are safe and tolerable over a 6-month study period and yield improvements in body composition, fatigue, depression, QoL, neurological disability and adipose-related inflammation in persons living with relapsing MS. Trial registration information Registered on ClinicalTrials.gov under registration number NCT03718247 , posted on 24 October 2018. First patient enrolment date: 1 November 2018. Link: https://clinicaltrials.gov/ct2/show/NCT03718247?term=NCT03718247&draw=2&rank=1 .
... The impact of a ketogenic diet on the lipid profile is a topic of great interest and controversy, as the weight loss achieved by a drastic reduction in carbohydrates is associated with a compensatory increase in fat intake, including saturated fat [558]. Furthermore, rapid weight loss promotes an increase (or no reduction) in LDL-c levels [559]. An increase in the size of the LDL-c molecule has been observed, but this does not seem to influence the risk of atherogenesis due to a lower trend of ectopic deposition in arterial walls [560,561]. ...
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Dietary risk factors play a fundamental role in the prevention and progression of atherosclerosis and PAD (Peripheral Arterial Disease). The impact of nutrition, however, defined as the process of taking in food and using it for growth, metabolism and repair, remains undefined with regard to PAD. This article describes the interplay between nutrition and the development/progression of PAD. We reviewed 688 articles, including key articles, narrative and systematic reviews, meta-analyses and clinical studies. We analyzed the interaction between nutrition and PAD predictors, and subsequently created four descriptive tables to summarize the relationship between PAD, dietary risk factors and outcomes. We comprehensively reviewed the role of well-studied diets (Mediterranean, vegetarian/vegan, low-carbohydrate ketogenic and intermittent fasting diet) and prevalent eating behaviors (emotional and binge eating, night eating and sleeping disorders, anorexia, bulimia, skipping meals, home cooking and fast/ultra-processed food consumption) on the traditional risk factors of PAD. Moreover, we analyzed the interplay between PAD and nutritional status, nutrients, dietary patterns and eating habits. Dietary patterns and eating disorders affect the development and progression of PAD, as well as its disabling complications including major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Nutrition and dietary risk factor modification are important targets to reduce the risk of PAD as well as the subsequent development of MACE and MALE.
... Walsh et al. found that after administration of a ketone ester (KE) there was no change in BDNF concentrations in healthy populations but later saw either sustained or increased BDNF following both KE ingestion and an Oral Glucose Tolerance Test in normal and overweight participants (Walsh et al., 2020(Walsh et al., , 2021. Two studies showed increased BDNF concentrations after a >8-week KD intervention in healthy weight adults (Mohorko et al., 2019;Paoli et al., 2021). Elevated NGF-β and BDNF concentrations are often discovered in obese populations during metabolic panel screening (Levinger et al., 2008;Atanassova et al., 2014;Lee et al., 2016). ...
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Background Ketogenic diets are a commonly used weight loss method, but little is known how variations in sodium content and ketones influence cognition and mood during the early keto-adaptation period.Objectives To investigate the effects of an exogenous ketone salt (KS) as part of a hypocaloric KD on mood and cognitive outcomes in overweight and obese adults. A secondary objective was to evaluate changes in biochemical markers associated with inflammatory and cognitive responses.Materials and methodsAdults who were overweight or obese participated in a 6-week controlled-feeding intervention comparing hypocaloric diets (∼75% of energy expenditure). KD groups received twice daily ketone salt (KD + KS; n = 12) or a flavor-matched placebo, free of minerals (KD + PL; n = 13). A separate group of age and BMI matched adults were later assigned to an isoenergetic low-fat diet (LFD; n = 12) as comparison to KD. Mood was assessed by shortened Profile of Mood States and Visual Analog Mood Scale surveys. Cognitive function was determined by the Automated Neuropsychological Assessment Metrics mental test battery.ResultsBoth KD groups achieved nutritional ketosis. Fasting serum glucose decreased in both KD groups, whereas glucose was unaffected in the LFD. Insulin decreased at week 2 and remained lower in all groups. At week 2, depression scores in the KD + PL group were higher compared to KD + KS. Performance in the math processing and go/no-go cognitive tests were lower for KD + PL and LFD participants, respectively, compared to KD + KS. Serum leptin levels decreased for all groups throughout the study but were higher for KD + KS group at week 6. Serum TNF-α steadily increased for LFD participants, reaching significance at week 6.Conclusion During a short-term hypocaloric diet, no indication of a consistent decline in mood or cognitive function were seen in participants following either KD, despite KD + PL being relatively low in sodium. WK2 scores of “anger” and “depression” were higher in the LFD and KD + PL groups, suggesting that KS may attenuate negative mood parameters during the early intervention stages.
... the key" and it should be used with caution for long term to avoid nutritional deficiencies [6][7][8][9][10][11][12]. ...
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... After a 12-week KD, obese adults lost weight, improved physical performance, cognitive function, eating behavior, and metabolic profile, according to a study conducted by Mohorko et al. [70]. The study found a significant reduction in appetite and body weight (men 18 9 kg vs. women −11 3 kg; p = 0.001), as well as enhanced physical performance (p = 0.001). ...
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This review aims to define the effectiveness of the ketogenic diet (KD) for the management of sarcopenic obesity. As the combination of sarcopenia and obesity appears to have multiple negative metabolic effects, this narrative review discusses the effects of the ketogenic diet as a possible synergic intervention to decrease visceral adipose tissue (VAT) and fatty infiltration of the liver as well as modulate and improve the gut microbiota, inflammation and body composition. The results of this review support the evidence that the KD improves metabolic health and expands adipose tissue γδ T cells that are important for glycaemia control during obesity. The KD is also a therapeutic option for individuals with sarcopenic obesity due to its positive effect on VAT, adipose tissue, cytokines such as blood biochemistry, gut microbiota, and body composition. However, the long-term effect of a KD on these outcomes requires further investigations before general recommendations can be made.
... Given prior research demonstrating the potential for ketogenic nutrition to enhance cognitive function [8,27], we aimed to develop a structured ketogenic nutrition program for older adults with MCI to improve adherence, which in turn may further enhance cognitive function. Prior work demonstrated that MI and CBT may be especially useful for targeting adherence. ...
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Background: The National Institutes of Health Obesity-Related Behavioral Intervention Trials model for intervention development was used to establish the feasibility and proof of concept of a motivational ketogenic nutrition adherence program for older adults with mild cognitive impairment. Methods: This was a single-arm, single-center feasibility trial. A comprehensive assessment protocol, including a clinical interview, neuropsychological testing, and genetic sequencing was used as an initial screening. Nine participants (aged 64-75) with possible amnestic mild cognitive impairment were consented for the intervention. Participants completed pre- and post-intervention neuropsychological assessments using the updated Repeatable Battery for Assessment of Neuropsychological Status. Participants tracked their macronutrient consumption using food diaries and ketone levels using urinalysis test strips daily. Mood and other psychosocial variables were collected through surveys, and qualitative exit interviews were completed. Results: 100% of participants who began the trial completed the 6-week ketogenic nutrition adherence program, including completion of the pre- and post-assessments. Eight participants achieved measurable levels of ketones during the program. The average self-rated adherence across the program was 8.7 out of 10. A Wilcoxon Signed-Rank test demonstrated significant improvement in cognitive performance from baseline (median = 88) to follow up (median = 96, Z = - 2.26, p = .024). The average difference in cognitive performance from baseline to follow-up was - 7.33 (95% CI - 12.85, - 1.82). Conclusions: Results supported the feasibility for moving to the next phase and demonstrated proof of concept for the intervention. The next step is a randomized pilot trial to test clinical signals of effect compared to a control condition. Trial registration: This trial was retrospectively registered with clinicaltrials.gov on July 13, 2021. The trial number is NCT04968041.
... Low carbohydrate, ketogenic foods are gaining considerable prominence, as the global demand to mitigate severe adversities of obesity and associated diseases has become a focal point in human health care [1][2][3][4][5][6][7][8][9][10]. Ketogenic foods are specific foods that support an individual in maintaining a state of nutritional ketosis. ...
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TCN006, a formulation of (R)-3-Hydroxybutyrate glycerides, is a promising ingredient for enhancing ketone intake of humans. Ketones have been shown to have beneficial effects on human health. To be used by humans, TCN006 must be determined safe in appropriately designed safety studies. The results of a bacterial reverse mutation assay, an in vitro mammalian micronucleus study, and 14-and 90-day repeat dose toxicity studies in rats are reported herein. In the 14- and 90-day studies, male and female Wistar rats had free access to drinking water containing 0, 75,000, 125,000 or 200,000 ppm TCN006 for 92 and 93 days, respectively. TCN006 tested negative for genotoxicity and the no observed adverse effect level (NOAEL) for toxicity in the 14- and 90-day studies was 200,000 ppm, the highest dose administered. In the longer term study, the mean overall daily intake of TCN006 in the 200,000 ppm groups was 14,027.9 mg/kg bw/day for males and 20,507.0 mg/kg bw/day for females. At this concentration, palatability of water was likely affected, which led to a decrease in water consumption in both males and females compared to respective controls. This had no effect on the health of the animals. Although the rats were administered very high levels of (R)-3-Hydroxybutyrate glycerides, there were no signs of ketoacidosis.
... (McClernon et al., 2007). Similarly, participants in an uncontrolled intervention study had experienced a decrease in insulin levels, BMI, and cognitive functions after 12 weeks (Mohorko et al., 2019). Improvements in metabolic pro le with KD have also been characterized by decreasing levels of triglycerides and low-density lipoprotein cholesterol (LDL) and increasing levels of high-density lipoprotein (HDL) cholesterol (Dashti et al., 2006;Yancy et al., 2004). ...
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Background: Bipolar disorder is a neurodevelopmental illness characterized by severe biphasic changes in mood, energy, or thought. Key underlying metabolic pathologies thought to play a role include dysfunction in energy metabolism. The purpose of this article is to review the findings to date of the effects of a low carbohydrate ketogenic diet (KD) on mood symptoms in preclinical and clinical models of bipolar illness. The review highlights the underlying metabolic pathologies of bipolar disorder (BD) and potential therapeutic effects of the KD on these pathologies. The article also explores the potential effects of a KD on metabolic health in BD, including proposed mechanisms of action. Summary: Recent findings support the idea that bipolar disorder, along with other psychiatric disease, may have roots of metabolic dysfunction: cerebral glucose hypometabolism, oxidative stress, as well as mitochondrial and neurotransmitter dysfunction which has downstream effects on synapse connections. A KD provides alternative fuel to the brain aside from glucose and is believed to contain beneficial neuroprotective effects, including stabilization of brain networks, reduction of inflammation and oxidative stress. Several beneficial metabolic effects on insulin resistance, weight, and lipids have been shown. Based on its effectiveness in treating epilepsy, the KD has garnered recent interest in its application for mood disorders as it may imitate the pharmacological effects of mood stabilizers, commonly prescribed agents in the treatment of both BD and epilepsy. Additionally, it may improve metabolic dysfunction often seen in BD and repair deficits in energy metabolism. Limited case studies on KD treatment in BD have been reported; however, studies addressing the potential therapeutic effects of KD on metabolic abnormalities in mental illness are promising. Literature of plausible mechanisms and reports of improvements in psychosis, cognition and mood symptoms have been increasing. Conclusions: Preliminary findings support further testing of a low carbohydrate KD as a potential therapeutic tool in repairing energy metabolism in bipolar illness. Further research and clinical trials are needed to evaluate the efficacy of a KD as a supplemental or co-treatment of bipolar illness and the first open-label trial testing the diet in bipolar illness is currently underway at Stanford.
... Já Mohorko et al, (2019) avaliaram perda de peso, performance, função cognitiva, comportamento alimentar e perfil metabólico de adultos obesos durante 12 semanas de dieta cetogênica associada ao exercício físico. Os parâmetros foram avaliados na 1ª, 2ª, 4ª, 8ª e 12ª semana. ...
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A obesidade é um problema de saúde pública mundial que favorece doenças crônicas não transmissíveis afetando a qualidade de vida e o risco de morte. Portanto é necessário combater essa epidemia através da perda de peso corporal. Dietas restritas em carboidrato são alvos de questionamentos sobre eficácia, mecanismo de ação e efeitos adversos. Sob essa definição existe um protocolo dietético que apresenta uma restrição severa em carboidratos, chamada dieta cetogênica que originalmente foi indicada no tratamento não-farmacológico da epilepsia, atualmente tem sido indicada para perda de peso sem ainda haver um consenso na literatura. O objetivo deste trabalho foi realizar uma revisão narrativa da literatura sobre a dieta cetogênica quanto sua eficiência na perda de peso, repercussões metabólicas, performance esportiva e efeitos colaterais. Foram selecionados 27 artigos científicos publicados nos últimos quatorze anos, disponíveis nos portais PubMed, Scielo, Google Acadêmico e BioMed. Em 24 trabalhos houve grupo controle. Em 19 artigos os participantes foram submetidos a protocolos sem restrições calóricas. Em todos os estudos foi constatada a redução de peso ponderal dos participantes. Após a revisão, considera-se que a dieta cetogênica é eficaz na perda de peso, melhora certos parâmetros bioquímicos, porém quando as calorias são controladas os resultados na perda de peso tendem a ser similares a uma dieta controle, embora haja diferenças na bioquímica sérica.
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Background The literature on correlates of nutrition has seen an increase in studies focused on functional consequences at the levels of neural, perceptual, and cognitive functioning. A range of measurement methodologies have been employed in these studies, and investigators and funding agencies have raised the questions of how and if these various methodologies are at all comparable. Objective To determine the extent to which three different sets of cognitive measures provide comparable information across two subsamples that shared culture and language but differed in terms of SES and academic preparation. Methods A total of 216 participants were recruited at two US universities. Each participant completed three sets of cognitive measures: one custom-designed set based on well-understood laboratory measures of cognition (COGTASKS), and two normed batteries (CANTAB, WAIS-IV) designed for assessing general cognitive function. Results The three sets differed with respect to the extent to which SES and educational preparation affected the results, with COGTASKS showing no differences due to testing location and WAIS-IV showing substantial differences. There were at best weak correlations among tasks sharing the same name or claiming to measure the same construct. Conclusions Comparability of measures of cognition cannot be assumed, even if measures have the same name or claim to assess the same construct. In selecting and evaluating different measures, construct validity and underlying biological mechanisms need to be at least as important as population norms and the ability to connect with existing literatures.
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Euglycemic diabetic ketoacidosis (DKA) is an acute life-threatening metabolic emergency characterized by ketoacidosis and relatively lower blood glucose (less than 11 mmol/L). The absence of hyperglycemia is a conundrum for physicians in the emergency department and intensive care units; it may delay diagnosis and treatment causing worse outcomes. Euglycemic DKA is an uncommon diagnosis but can occur in patients with type 1 or type 2 diabetes mellitus. With the addition of sodium/ glucose cotransporter-2 inhibitors in diabetes mellitus management, euglycemic DKA incidence has increased. The other causes of euglycemic DKA include pregnancy, fasting, bariatric surgery, gastroparesis, insulin pump failure, cocaine intoxication, chronic liver disease and glycogen storage disease. The pathophysiology of euglycemic DKA involves a relative or absolute carbohydrate deficit, milder degree of insulin deficiency or resistance and increased glucagon/insulin ratio. Euglycemic DKA is a diagnosis of exclusion and should be considered in the differential diagnosis of a sick patient with a history of diabetes mellitus despite lower blood glucose or absent urine ketones. The diagnostic workup includes arterial blood gas for metabolic acidosis, serum ketones and exclusion of other causes of high anion gap metabolic acidosis. Euglycemic DKA treatment is on the same principles as for DKA with correction of dehydration, electrolytes deficit and insulin replacement. The dextrose-containing fluids should accompany intravenous insulin to correct metabolic acidosis, ketonemia and to avoid hypoglycemia.
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Obesity remains a serious relevant public health concern throughout the world despite related countermeasures being well understood (i.e., mainly physical activity and an adjusted diet). Among different nutritional approaches, there is a growing interest in ketogenic diets (KDs) to manipulate body mass (BM) and to enhance fat mass (FM) loss. KDs reduce the daily amount of carbohydrate intake drastically. This results in increased fatty acid utilization, leading to an increase in blood ketone bodies (KBs) (acetoacetate [AcAc], 3-β-hydroxybutyrate [BHB], and acetone), and therefore metabolic ketosis. For many years, nutritional intervention studies have focused on reducing dietary fat with little or conflicting positive results over the long-term. Moreover, current nutritional guidelines for athletes propose carbohydrate-based diets to augment muscular adaptations. This review discusses the physiological basis of KDs and their effects on BM reduction and body composition improvements in sedentary individuals combined with different types of exercise (resistance training [RT] or endurance training [ET]) in individuals with obesity and athletes. Ultimately, we discuss the strengths and the weaknesses of these nutritional interventions together with precautionary measures that should be observed in both individuals with obesity and athletic populations. A literature search from 1921 to April 2021 using MEDLINE, GOOGLE SCHOLAR, PUBMED, WEB OF SCIENCE, SCOPUS, and SPORTDISCUS databases were used to identify relevant studies. In summary, based on the current evidence, KDs are an efficient method to reduce BM and body fat in both individuals with obesity and athletes. However, these positive impacts are mainly because of the appetite suppressive effects of KDs, which can decrease daily calorie intake. Therefore, KDs do not have any superior benefits to non-KDs in BM and body fat loss in individuals with obesity and athletic populations in an isocaloric situation. In sedentary individuals with obesity, it seems that fat-free mass (FFM) changes appear to be as great, if not greater, than decreases following a low-fat diet (LFD). In terms of lean mass, it seems that following a KD can cause FFM loss in resistance-trained individuals. In contrast, the FFM-preserving effects of KDs are more efficient in endurance-trained compared to resistance-trained individuals.
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Purpose This study aims to evaluate the effects of a VLCKD combined with omega-3 supplementation (VLCKD diet only lasted for some weeks, and it was followed by a non-ketogenic LCD for the rest of the study period) on body composition, visceral fat, satiety hormones, inflammatory and metabolic markers. Methods It has been performed a pilot open label study lasted 90 days, in a cohort of 12 women with class I obesity aged 18 to 65 years. Data on body composition (evaluated by Dual X-Ray Absorptiometry—DXA), visceral fat, satiety hormones, inflammatory and metabolic markers were recorded. Results This study showed a body weight reduction mean difference over time of −13.7 kg and the waist circumference mean difference decrease of −13.3 cm. Also, the fat mass (FM) decreased—9.1 kg and visceral adipose tissue (VAT)—0.41 kg. No effects on fat-free mass (FFM) have been reported. Improvements were observed in the satiety hormones, with increased ghrelin and decreased leptin, and also in the metabolic profiles. Conclusions A VLCKD combined with omega-3 supplementation appears to be an effective strategy for promoting an high loss of FM with preservation of FFM in patients with class I obesity.
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Introduction: Ketogenic diet (KD) therapy has been used as a dietary intervention in drug-resistant epilepsy for several years. Research currently suggests that KD therapy may carry neuroprotective and cognition enhancing effects for individuals with non-epileptic conditions as well as for healthy individuals. Therefore, KD may have potential as a non-invasive, nutritional treatment approach for difficult to manage conditions such as neurodegenerative illnesses or mood disorders. The aim of this review is to summarize the available evidence on ketogenic interventions and the resulting cognitive outcomes. Materials and Methods: The paper was based on PRISMA 2020 guidelines. The search was conducted in June 2021 on the following databases: CENTRAL, PubMed, EMBASE, PsycInfo, Web of Science. The search yielded 2014 studies, of which 49 were included. Results: There were 22 animal studies assessing murine models and 27 studies on humans. The primary indications in these studies were epileptic conditions, neurodegenerative disorders, cognitive impairment, and healthy populations. Discussion: Administration of KD seems to confer cognitive-enhancing effects in areas such as working memory, reference memory and attention. Studies found that KD treatment in animals has the potential to alleviate age-related cognitive decline. Over 80% of the 27 human studies reported a favourable effect of intervention, and none reported a detrimental effect of KD. While these findings suggest that KD may improve the functioning of certain cognitive domains, definitive conclusions were limited by studies with small sample sizes, the absence of controls and randomization, and the lack of objective measures of cognition.
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Background : Obesity is considered a significant public health problem in Thailand. This study was conducted to compare the impact of mobile health education messages verses face-to-face consultation on weight reduction among overweight female university students. Methods : This Quasi-experimental study comprised three groups: a control group, a group receiving mobile health education, and a group receiving face-to-face consultation. Each group contained 26 participants taking part over a period of 12 weeks, with a 12-week follow-up thereafter. The data analysis used two-way repeated measures ANOVA with least significant difference testing. The study was ethically approved at Chulalongkorn University, Thailand. Results : The results revealed that the intervention found significant results in weight reduction among the respondents ( p < 0.05). In addition, both intervention groups significantly improved their health belief, social support, and health behavior scores in comparison to the control group ( p < 0.001). The results show that the average scores for social support for eating and exercise at baseline were significantly lower than at post-intervention or follow-up ( p < 0.001). In addition, the results of both aspects of social support showed that the average social support score at post-intervention was significantly higher than at follow-up. Furthermore, the health behavior score measured post-intervention was higher than at follow-up. There was a statistically significant difference in average metabolism during physical activity ( p < 0.001) but no statistical difference in average eating behavior score. Conclusion : The study found that the use of mobile health education to deliver health programs facilitates communication between the healthcare provider and individual, and can empower adolescent females in their pursuit of weight loss by improving their attitudes and knowledge, leading to better health behavior. Keywords Electronic health education, Facebook, health education, health belief model, social support, obesity, Thailand, health behaviors
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Background The resting metabolic rate (RMR) decrease, observed after an obesity reduction therapy is a determinant of a short-time weight regain. Thus, the objective of this study was to evaluate changes in RMR, and the associated hormonal alterations in obese patients with a very low-calorie ketogenic (VLCK)-diet induced severe body weight (BW) loss. Method From 20 obese patients who lost 20.2 kg of BW after a 4-months VLCK-diet, blood samples and body composition analysis, determined by DXA and MF-Bioimpedance, and RMR by indirect calorimetry, were obtained on four subsequent visits: visit C-1, basal, initial fat mass (FM) and free fat mass (FFM); visit C-2, − 7.2 kg in FM, − 4.3 kg in FFM, maximal ketosis; visit C-3, − 14.4 kg FM, − 4.5 kg FFM, low ketosis; visit C-4, − 16.5 kg FM, − 3.8 kg FFM, no ketosis. Each subject acted as his own control. ResultsDespite the large BW reduction, measured RMR varied from basal visit C-1 to visit C-2, − 1.0%; visit C-3, − 2.4% and visit C-4, − 8.0%, without statistical significance. No metabolic adaptation was observed. The absent reduction in RMR was not due to increased sympathetic tone, as thyroid hormones, catecholamines, and leptin were reduced at any visit from baseline. Under regression analysis FFM, adjusted by levels of ketonic bodies, was the only predictor of the RMR changes (R2 = 0.36; p < 0.001). Conclusion The rapid and sustained weight and FM loss induced by VLCK-diet in obese subjects did not induce the expected reduction in RMR, probably due to the preservation of lean mass. Trial registrationThis is a follow up study on a published clinical trial.
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Objective The low-carbohydrate, high-fat (LCHF) diet is becoming increasingly employed in clinical dietetic practice as a means to manage many health-related conditions. Yet, it continues to remain contentious in nutrition circles due to a belief that the diet is devoid of nutrients and concern around its saturated fat content. This work aimed to assess the micronutrient intake of the LCHF diet under two conditions of saturated fat thresholds. Design In this descriptive study, two LCHF meal plans were designed for two hypothetical cases representing the average Australian male and female weight-stable adult. National documented heights, a body mass index of 22.5 to establish weight and a 1.6 activity factor were used to estimate total energy intake using the Schofield equation. Carbohydrate was limited to <130 g, protein was set at 15%–25% of total energy and fat supplied the remaining calories. One version of the diet aligned with the national saturated fat guideline threshold of <10% of total energy and the other included saturated fat ad libitum. Primary outcomes The primary outcomes included all micronutrients, which were assessed using FoodWorks dietary analysis software against national Australian/New Zealand nutrient reference value (NRV) thresholds. Results All of the meal plans exceeded the minimum NRV thresholds, apart from iron in the female meal plans, which achieved 86%–98% of the threshold. Saturated fat intake was logistically unable to be reduced below the 10% threshold for the male plan but exceeded the threshold by 2 g (0.6%). Conclusion Despite macronutrient proportions not aligning with current national dietary guidelines, a well-planned LCHF meal plan can be considered micronutrient replete. This is an important finding for health professionals, consumers and critics of LCHF nutrition, as it dispels the myth that these diets are suboptimal in their micronutrient supply. As with any diet, for optimal nutrient achievement, meals need to be well formulated.
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Objective: The ketones d-β-hydroxybutyrate (BHB) and acetoacetate are elevated during prolonged fasting or during a "ketogenic" diet. Although weight loss on a ketogenic diet may be associated with decreased appetite and altered gut hormone levels, it is unknown whether such changes are caused by elevated blood ketones. This study investigated the effects of an exogenous ketone ester (KE) on appetite. Methods: Following an overnight fast, subjects with normal weight (n = 15) consumed 1.9 kcal/kg of KE, or isocaloric dextrose (DEXT), in drinks matched for volume, taste, tonicity, and color. Blood samples were analyzed for BHB, glucose, insulin, ghrelin, glucagon-like peptide 1 (GLP-1), and peptide tyrosine tyrosine (PYY), and a three-measure visual analogue scale was used to measure hunger, fullness, and desire to eat. Results: KE consumption increased blood BHB levels from 0.2 to 3.3 mM after 60 minutes. DEXT consumption increased plasma glucose levels between 30 and 60 minutes. Postprandial plasma insulin, ghrelin, GLP-1, and PYY levels were significantly lower 2 to 4 hours after KE consumption, compared with DEXT consumption. Temporally related to the observed suppression of ghrelin, reported hunger and desire to eat were also significantly suppressed 1.5 hours after consumption of KE, compared with consumption of DEXT. Conclusions: Increased blood ketone levels may directly suppress appetite, as KE drinks lowered plasma ghrelin levels, perceived hunger, and desire to eat.
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Background and aims: Very low-calorie ketogenic (VLCK) diets have been consistently shown to be an effective obesity treatment, but the current evidence for its acid-base safety is limited. The aim of the current work was to evaluate the acid-base status of obese patients during the course of a VLCK diet. Method: Twenty obese participants undertook a VLCK diet for 4 months. Anthropometric and biochemical parameters, and venous blood gases were obtained on four subsequent visits: visit C-1 (baseline); visit C-2, (1-2 months); maximum ketosis; visit C-3 (2-3 months), ketosis declining; and visit C-4 at 4 months, no ketosis. Results were compared with 51 patients that had an episode of diabetic ketoacidosis as well as with a group that underwent a similar VLCK diet in real life conditions of treatment. Results: Visit C1 blood pH (7.37 ± 0.03); plasma bicarbonate (24.7 ± 2.5 mmol/l); plasma glucose (96.0 ± 11.7 mg/l) as well as anion gap or osmolarity were not statistically modified at four months after a total weight reduction of 20.7 kg in average and were within the normal range throughout the study. Even at the point of maximum ketosis all variables measured were always far from the cut-off points established to diabetic ketoacidosis. Conclusion: During the course of a VLCK diet there were no clinically or statistically significant changes in glucose, blood pH, anion gap and plasma bicarbonate. Hence the VLCK diet can be considered as a safe nutritional intervention for the treatment of obesity in terms of acid-base equilibrium.
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Metabolic adaptations occur with weight loss that result in increased hunger with discordant simultaneous reductions in energy requirements—producing the so-called energy gap in which more energy is desired than is required. The increased hunger is associated with elevation of the orexigenic hormone ghrelin and decrements in anorexigenic hormones. The lower total daily energy expenditure with diet-induced weight loss results from (1) a disproportionately greater decrease in circulating leptin and resting metabolic rate (RMR) than would be predicted based on the decline in body mass, (2) decreased thermic effect of food (TEF), and (3) increased energy efficiency at work intensities characteristic of activities of daily living. These metabolic adaptations can readily promote weight regain. While more experimental research is needed to identify effective strategies to narrow the energy gap and attenuate weight regain, some factors contributing to long-term weight loss maintenance have been identified. Less hunger and greater satiation have been associated with higher intakes of protein and dietary fiber, and lower glycemic load diets. High levels of physical activity are characteristic of most successful weight maintainers. A high energy flux state characterized by high daily energy expenditure and matching energy intake may attenuate the declines in RMR and TEF, and may also result in more accurate regulation of energy intake to match daily energy expenditure.
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Background/objective: Diet-induced weight loss (WL) leads to increased hunger and reduced fullness feelings, increased ghrelin and reduced satiety peptides concentration (glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK) and peptide YY (PYY)). Ketogenic diets seem to minimise or supress some of these responses. The aim of this study was to determine the timeline over which changes in appetite occur during progressive WL with a ketogenic very-low energy diet (VLED). Subjects/methods: Thirty-one sedentary adults (18 men), with obesity (BMI: 37±4.5 kg/m(2)) underwent 8 weeks (wks) of a VLED followed by 4 wks of weight maintenance. Body weight and composition, subjective feelings of appetite and appetite related hormones (insulin, active ghrelin (AG), active GLP-1, total PYY and CCK) were measured in fasting and postprandially, at baseline, on day 3 of the diet, 5 and 10% WL, and at wks 9 and 13.Data shown as mean±s.d. Results: A significant increase in fasting hunger was observed by day 3 (2±1% WL), (P<0.01), 5% WL (12±8 days) (P<0.05) and wk 13 (17±2% WL) (P<0.05). Increased desire to eat was observed by day 3 (P<0.01) and 5% WL (P<0.05). Postprandial prospective food consumption was significantly reduced at wk 9 (16±2% WL) (P<0.01). Basal total PYY was significantly reduced at 10% WL (32±8 days) (P<0.05). Postprandial active GLP-1 was increased at 5% WL (P<0.01) and CCK reduced at 5 and 10% WL (P<0.01, for both) and wk 9 (P<0.001). Basal and postprandial AG were significantly increased at wk 13 (P<0.001, both). Conclusion: WL with a ketogenic VLED transiently increases the drive to eat up to 3 weeks (5% WL). After that, and while participants are ketotic, a 10-17% WL is not associated with increased appetite. However, hunger feelings and AG concentrations increase significantly from baseline, once refeeding occurs.International Journal of Obesity accepted article preview online, 25 April 2017. doi:10.1038/ijo.2017.96.
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There is a direct relationship between fructose intake and serum levels of uric acid (UA), which is the final product of purine metabolism. Recent preclinical and clinical evidence suggests that chronic hyperuricemia is an independent risk factor for hypertension, metabolic syndrome, and cardiovascular disease. It is probably also an independent risk factor for chronic kidney disease, Type 2 diabetes, and cognitive decline. These relationships have been observed for high serum UA levels (>5.5 mg/dL in women and >6 mg/dL in men), but also for normal to high serum UA levels (5–6 mg/dL). In this regard, blood UA levels are much higher in industrialized countries than in the rest of the world. Xanthine-oxidase inhibitors can reduce UA and seem to minimize its negative effects on vascular health. Other dietary and pathophysiological factors are also related to UA production. However, the role of fructose-derived UA in the pathogenesis of cardiometabolic disorders has not yet been fully clarified. Here, we critically review recent research on the biochemistry of UA production, the relationship between fructose intake and UA production, and how this relationship is linked to cardiometabolic disorders.
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Background The ketogenic diet (KD) has been used in treatment-resistant epilepsy since the 1920’s. It has been researched in a variety of neurological conditions in both animal models and human trials. The aim of this review is to clarify the potential role of KD in psychiatry. Methods Narrative review of electronic databases PubMED, PsychINFO and Scopus. Results The search yielded 15 studies that related the use of KD in mental disorders including anxiety, depression, bipolar disorder, schizophrenia, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). These studies comprised nine animal models, four case studies and two open-label studies in humans. In anxiety, exogenous ketone supplementation reduced anxiety-related behaviours in a rat model. In depression, KD significantly reduced depression-like behaviours in rat and mice models in two controlled studies. In bipolar disorder, one case study reported a reduction in symptomatology a second case study no improvement. In schizophrenia, an open-label study in female patients (n=10) reported reduced symptoms after two weeks of KD, a single case study reported no improvement. In a brief report, three weeks of KD in a mouse model normalized pathological behaviours. In ASD an open-label study in children (n=30) reported no significant improvement; one case study a pronounced and sustained response to KD. In ASD, in four controlled animal studies, KD significantly reduced ASD-related behaviours in mice and rats. In ADHD, in one controlled trial of KD in dogs with co-morbid epilepsy, both conditions significantly improved. Conclusions Despite its long history in neurology, the role of KD in mental disorders is unclear. Half of the published studies are based on animal models of mental disorders with limited generalizability to the analogue conditions in humans. The review lists some major limitations including the lack of measuring ketone levels in four studies and the issue of compliance to the rigid diet in humans. Currently there is insufficient evidence for the use of KD in mental disorders and it is not a recommended treatment option. Future research should include long-term, prospective, randomized, placebo-controlled crossover dietary trials to examine the effect of KD in various mental disorders.
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