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Ketone bodies: acetoacetate (AcAc) is the principle ketone body. It is produced and utilized during intermediary metabolism and other ketone bodies are derived from it. Acetone is produced by the spontaneous decarboxylation of acetoacetate and is important from the clinical point of view because it is responsible for the fruity sweet odour of infant ketoacidosis. β -Hydroxybutyric acid is produced via the reduction of AcAc. From a strictly biochemical point of view it is not actually a ketone body since the ketonic moiety is reduced to a hydroxyl group; it is though grouped among the ketone bodies. 3HB is relatively stable biochemically and is transported to the tissues where it is reconverted to AcAc.
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Obesity is reaching epidemic proportions and is a strong risk factor for a number of cardiovascular and metabolic disorders such as hypertension, type 2 diabetes, dyslipidemia, atherosclerosis, and also certain types of cancers. Despite the constant recommendations of health care organizations regarding the importance of weight control, this goal o...
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... the second issue, the CNS cannot use fatty acids as an energy source (because they do not cross the blood-brain barrier), thus glucose is ordinarily the sole fuel for the human brain [24]. After 3-4 days of fasting or a very low carbohydrate diet the CNS needs an alternative energy source [19][20][21][22] and this is derived from the overproduction of acetyl-CoA which leads to the production of so-called ketone bodies (KB): acetoacetate (AcAc), β-hydroxybutyric acid (BHB) and acetone (Figures 1 and 2). This process is called ketogenesis and occurs principally in the mitochondrial matrix in the liver [25]. ...
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Citations
... The therapeutic effect of very low carbohydrate diets or ketogenic diets (KDs), which typically restrict carbohydrate intake to less than 20 g per day [108], has been discussed. After several days on a very low carbohydrate diet, glycogen reserves are depleted, and ketone bodies are produced to maintain energy production within the mitochondria [75]. ...
Migraine is a prevalent neurological disorder characterized by significant disability and triggered by various factors, including dietary habits. This review explores the complex relationship between diet and migraine, highlighting both triggering and protective roles of dietary patterns and specific nutrients. Evidence suggests that certain foods, such as alcohol, caffeine, chocolate, MSG, nitrates, and tyramine, can trigger migraines in susceptible individuals. Conversely, dietary interventions, including carbohydrate-restricted diets, ketogenic diets, vitamin D3 supplementation, omega-3 fatty acids, Mediterranean dietary patterns, and increased water intake, have shown potential in reducing migraine frequency and severity. Observational studies also indicate that maintaining a healthy diet, rich in fruits and vegetables and low in processed foods, is associated with better migraine outcomes. The effectiveness of these interventions varies among individuals, underscoring the importance of personalized approaches. Future studies should further explore the role of diet in migraine management, focusing on randomized trials to establish causality and refine dietary recommendations for patients.
... Physical activity reduces substrate availability for DNL by increasing glucose uptake in muscle tissue, thereby lowering blood glucose and insulin levels [36]. Similarly, ketogenic diets limit carbohydrate intake and stimulate lipolysis, which shifts the body toward fat as the primary energy source and suppresses DNL [37][38][39]. Intermittent fasting cycles modulate insulin and glucagon levels, favoring lipid oxidation over lipogenesis during fasting periods, which can reduce hepatic lipid accumulation and improve metabolic flexibility [40]. ...
De novo lipogenesis (DNL) is a metabolic pathway that converts carbohydrates into fatty acids, primarily occurring in the liver and, to a lesser extent, in adipose tissue. While hepatic DNL is highly responsive to dietary carbohydrate intake and regulated by insulin via transcription factors like SREBP-1c, adipose DNL is more modest and less sensitive to dietary overfeeding. Dysregulated DNL contributes to metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). Lifestyle interventions, such as physical exercise, ketogenic diets, and time-restricted eating (TRE) offer promising strategies to regulate DNL and improve metabolic health. Physical exercise enhances glucose uptake in muscles, reduces insulin levels, and promotes lipid oxidation, thereby suppressing hepatic DNL. Endurance and resistance training also improve mitochondrial function, further mitigating hepatic triglyceride accumulation. Ketogenic diets shift energy metabolism toward fatty acid oxidation and ketogenesis, lower insulin, and directly downregulate lipogenic enzyme activity in the liver. TRE aligns feeding with circadian rhythms by optimizing AMP-activated protein kinase (AMPK) activation during fasting periods, which suppresses DNL and enhances lipid metabolism. The combined effects of these interventions demonstrate significant potential for improving lipid profiles, reducing hepatic triglycerides, and preventing lipotoxicity. By addressing the distinct roles of the liver and adipose DNL, these strategies target systemic and localized lipid metabolism dysregulation. Although further research is needed to fully understand their long-term impact, these findings highlight the transformative potential of integrating these approaches into clinical practice to manage metabolic disorders and their associated complications.
... This condition arises because of insulin deficiency, which results in the production of excessive ketones that can lead to metabolic acidosis [1][2][3]. However, supraphysiological ketosis can also be achieved in situations where glucose availability is low, such as following a low-carbohydrate diet or fasting [4]. Recently, a new form of ketosis known as nutritional ketosis has been introduced, thanks to the development of ketone esters and similar products for oral consumption. ...
... This phase lasts 8-12 weeks and is characterized by the production of ketone bodies, which provide energy to the nervous system, heart, kidneys, and skeletal muscle, primarily from lipids (Castellana et al., 2020). Ketogenesis is also believed to induce an anorexigenic effect, contributing to as much as 80% of the weight loss observed during this period (Merra et al., 2016;Paoli, 2014). Micronutrient supplementation, including vitamins, potassium, sodium, magnesium, calcium, and omega-3 fatty acids, is often recommended during this phase (Bakhach et al., 2016;Chapela et al., 2024a;Merra et al., 2016). ...
The Very Low-Energy Ketogenic Therapy (VLEKT) is a structured, multi-phase dietary regimen characterized by a carbohydrate intake of less than 50 g/day and a daily caloric intake of fewer than 800 kcal, which induces ketosis and facilitates significant weight loss. Evidence suggests that this nutritional therapy can improve glycemic control, lipid profiles, and blood pressure, making it a promising option for managing type 2 diabetes (T2D) and reducing cardiovascular risk. These benefits are achieved through reductions in triglycerides and low-density lipoprotein cholesterol (LDL-c), alongside increases in high-density lipoprotein cholesterol (HDL-c). However, the effects of the VLEKT on lipid metabolism remain controversial. The review emphasizes the urgent need for further research to validate the long-term safety and efficacy of the VLEKT. It also highlights the critical role of personalized dietary plans, supervised by healthcare professionals, to optimize health outcomes and address individual patient needs.
... Keto diet's hallmark is the reduction in the blood sugar levels and an increase in ketones. In Keto diet, one burns fat and ketones as the main fuel source [67]. ...
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... This has necessitated the exploration of alternative, sophisticated treatments that can potentially mitigate damage as adjuvant therapies [1]. Over the past few decades, the ketogenic diet (KD) has emerged as a complementary therapy for a variety of systemic diseases, including metabolic disorders such as obesity [2] and diabetes [3], cardiovascular diseases [4], polycystic ovary syndrome [5], non-alcoholic fatty liver disease, and certain types of cancer [6][7][8]. Recently, benefits have also been reported for neurological diseases characterized by chronic neuroinflammation [9][10][11][12][13], such as epilepsy [14], Alzheimer's disease (AD), Parkinson's disease, traumatic brain injury, cerebral ischemia, multiple sclerosis (MS), Huntington's disease (HD) [15], and brain tumors like gliomas [16,17]. ...
Background: The ketogenic diet (KD), high in fat and low in carbohydrates, was introduced in the 1920s as a non-pharmacological treatment for refractory epilepsy. Although its mechanism of action is not fully understood, beneficial effects have been observed in neurological diseases such as epilepsy, Alzheimer’s disease, and Parkinson’s disease. Objective: This review examines the impact of the ketogenic diet and its molecular and neuroglial effects as a complementary therapy for neurological diseases. Discussion: KD is associated with neuroprotective and antioxidant effects that improve mitochondrial function, regulate neurotransmitter flow, and reduce neuroinflammation and oxidative stress. Glial cells play an essential role in the utilization of ketone bodies (KBs) within the central nervous system’s metabolism, particularly during ketosis induced by the KD. Thus, the KD represents a broad and promising strategy that involves both neurons and glial cells, with a molecular impact on brain metabolism and neuroinflammatory homeostasis. Conclusion: Multiple molecular mechanisms have been identified to explain the benefits of the KD in neurological diseases; however, further experimental and clinical studies are needed to address various molecular pathways in order to achieve conclusive results.
... In fact, 65% of the world's population live in countries where the mortality of overweight and obesity is higher than it of underweight. Obesity is considered as one of the main risks for cardiovascular disease and along with dyslipidaemia, hypertension and diabetes contributes to the metabolic syndrome [13]. A number of strategies have been proposed to reduce energy intake and increase physical activities. ...
... Diet is the most controversial topic about weight control, with different diets suggested to achieve this goal but little scientific evidence that one diet is superior to another. The most commonly accepted dietary strategy is based on relatively high levels of carbohydrates and low fat content, but different studies have shown the priority in terms of weight loss of a LCD compared to a low-fat one given that these low fat diets contribute only modest weight losses and suffer from low long-term adherence issues [11,13]. The KDs are recommended to be more adopted as an effective treatment of obesity-related problems. ...
... Conversely, some researchers claim that the results obtained with KDs could be attributed to a reduction in appetite due to higher satiety effect of proteins or to some effects on appetite control hormones. Others suggest a possible direct appetite suppressant action of the ketone bodies [13]. ...
As the demand for weight loss increases, the ketogenic diet (KD) has gradually attracted public attention and become one of the most popular dietary choices. This diet is characterized by high fat and low carbohydrates and was originally used to treat epilepsy. In recent years, studies have shown that KD has potential benefits in controlling obesity, improving metabolic syndrome, reducing insulin requirements in patients with type 2 diabetes, and alleviating inflammation. However, the effectiveness, safety, and risks of KD during pregnancy still need to be further verified. This article aims to explore the benefits and risks of KD as a dietary treatment and to clarify the differences between ketogenic diets for epilepsy and obesity. Studies have shown that KD improves multiple health indicators by inducing ketone body production and has therapeutic potential in certain neurodegenerative diseases. However, KD is also accompanied by certain side effects, such as hypoglycemia, digestive problems, and malnutrition, especially in children and elderly patients. Although KD performs well in controlling weight and improving blood sugar levels, its effects on cardiovascular disease, microbiome regulation, and cancer control need to be further studied. This article reveals the potential therapeutic value of KD for multiple diseases through a comprehensive evaluation of existing research results and emphasizes the importance of future research on dietary recommendations to promote health improvement.
... Furthermore, we determined that the number of participants who were in the obese and severe obese categories before the intervention decreased after the intervention. Similar to our findings, previous studies conducted especially in obese populations have reported that the KD provides BW loss and an improvement in cardiometabolic risk factors [28,29]. Another study evaluating the effects of a KD without energy restriction for 6 weeks in healthy adults showed significant decreases in BW and body fat percentage after the KD [30]. ...
Background/Objectives: The ketogenic diet (KD) is a dietary model that can impact metabolic health and microbiota and has been widely discussed in recent years. This study aimed to evaluate the effects of a 6-week KD on biochemical parameters, gut microbiota, and fecal short-chain fatty acids (SCFAs) in women with overweight/obesity. Methods: Overall, 15 women aged 26–46 years were included in this study. Blood samples, fecal samples, and anthropometric measurements were evaluated at the beginning and end of this study. Results: After KD, the mean body mass index decreased from 29.81 ± 4.74 to 27.12 ± 4.23 kg/m², and all decreases in anthropometric measurements were significant (p < 0.05). Fasting glucose, insulin, homeostasis model assessment of insulin resistance, hemoglobin A1C, urea, and creatinine levels decreased, whereas uric acid levels increased (p < 0.05). Furthermore, increased serum zonulin levels were noted (p = 0.001), whereas fecal butyrate, propionate, acetate, and total SCFA levels decreased (p < 0.05). When the changes in microbiota composition were examined, a decrease in beta diversity (p = 0.001) was observed. After the intervention, a statistically significant increase was noted in the Firmicutes/Bacteroidetes ratio (p = 0.001). Although Oscilibacter, Blautia, and Akkermensia relative abundances increased, Prevotella relative abundance and Bifidobacter abundance, which were the dominant genera before the KD, decreased. Moreover, the abundance of some pathogenic genera, including Escherichia, Klebsilella, and Listeria, increased. Conclusions: In healthy individuals, KD may cause significant changes in microbial composition, leading to dysbiosis and long-term adverse outcomes with changes in serum zonulin and fecal SCFA levels.
... For example, some studies use a KD formulated with a protein ratio significantly lower than that of a standard control diet (CD), which may confound the effects of KD given the pivotal role of protein restriction in weight loss 17 and aging 18 . As is the case with humans 19 , the composition, duration, periodicity, and feeding pattern of a KD regimen can all alter its effect on obesity. ...
... The KD, commonly known for its low carbohydrate and high fat intake, is designed to promote weight loss (28). Numerous studies have demonstrated that ketogenic diets can lead to rapid weight loss (50)(51)(52). While initial weight loss and reduction in adipose tissue occur as a result of strict adherence to this diet, these effects tend to diminish over time, becoming comparable to other weight loss dietary approaches after 1 year (53,54). ...
Introduction
Obesity is a growing public health issue, especially among young adults, with long-term management strategies still under debate. This prospective study compares the effects of caloric restriction and isocaloric diets with different macronutrient distributions on body composition and anthropometric parameters in obese women during a 12-week weight loss program, aiming to identify the most effective dietary strategies for managing obesity-related health outcomes.
Methods
A certified clinical nutritionist assigned specific diets over a 12-week period to 150 participants, distributed as follows: hypocaloric diets—low-energy diet (LED, 31 subjects) and very low-energy diet (VLED, 13 subjects); isocaloric diets with macronutrient distribution—low-carbohydrate diet (LCD, 48 subjects), ketogenic diet (KD, 23 subjects), and high-protein diet (HPD, 24 subjects); and isocaloric diet without macronutrient distribution—time-restricted eating (TRE, 11 subjects). Participants were dynamically monitored using anthropometric parameters: body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and bioelectrical impedance analysis (BIA) using the TANITA Body Composition Analyzer BC-418 MA III (T5896, Tokyo, Japan) at three key intervals—baseline, 6 weeks, and 12 weeks. The following parameters were evaluated: body weight, basal metabolic rate (BMR), percentage of total body fat, trunk fat, muscle mass, fat-free mass, and hydration status.
Results
All diets led to weight loss, but differences emerged over time. The TRE model resulted in significantly less weight loss compared to LED at the final follow-up (6.30 kg, p < 0.001), similar to the VLED (4.69 kg, p < 0.001). Isocaloric diets with varied macronutrient distributions showed significant weight loss compared to LED (p < 0.001). The KD reduced waist circumference at both 6 and 12 weeks (−4.08 cm, p < 0.001), while significant differences in waist-to-hip ratio reduction were observed across diet groups at 12 weeks (p = 0.01). Post-hoc analysis revealed significant fat mass differences at 12 weeks, with HPD outperforming IF (p = 0.01) and VLED (p = 0.003). LCD reduced trunk fat at 6 weeks (−2.36%, p = 0.001) and 12 weeks (−3.79%, p < 0.001). HPD increased muscle mass at 12 weeks (2.95%, p = 0.001), while VLED decreased it (−2.02%, p = 0.031). TRE showed a smaller BMR reduction at 12 weeks compared to LED.
Conclusion
This study highlights the superior long-term benefits of isocaloric diets with macronutrients distribution over calorie-restrictive diets in optimizing weight, BMI, body composition, and central adiposity.