Core Insights - The article discusses the recent breakthrough research on the ketogenic diet and its metabolic effects, particularly focusing on the discovery of a new metabolic pathway involving the ketone body β-hydroxybutyrate (BHB) and its amino acid derivatives that can effectively suppress food intake and control body weight [5][11]. Group 1: Research Findings - A joint study from Baylor College of Medicine and Stanford University identified a new metabolic pathway involving BHB that produces BHB-amino acids, which can significantly inhibit food intake [5][11]. - The research was inspired by a previous finding that a compound formed from lactate and phenylalanine (Lac-Phe) can suppress appetite and aid weight loss in mice [8][11]. - The study confirmed that the enzyme carnosine dipeptidase 2 (CNDP2) can catalyze the reaction between BHB and amino acids, leading to the synthesis of BHB-amino acids in various tissues [11][12]. Group 2: Experimental Results - Experiments showed that BHB-amino acid levels increased with higher ketone body levels, with the ketogenic diet group exhibiting the most significant changes [12]. - In a diet-induced obesity (DIO) mouse model, the injection of BHB-phenylalanine (50 mg/kg) significantly reduced food intake without affecting water consumption, exercise capacity, or other metabolic parameters [13][14]. - The mechanism of BHB-phenylalanine's appetite suppression was found to be independent of known appetite control pathways, indicating a novel regulatory pathway for food intake [14]. Group 3: Implications for Human Health - The study also demonstrated that the metabolic pathway involving BHB-amino acids is likely conserved in humans, as evidenced by increased plasma BHB-amino acid levels following a ketogenic diet in human volunteers [14]. - The researchers suggest that while the study focused on energy metabolism, BHB-amino acids may have implications for neurodegenerative diseases, inflammatory responses, cancer progression, and age-related conditions, warranting further investigation [14].

Core Viewpoint - The article discusses the rising popularity of the ketogenic diet and its mechanisms for weight loss, highlighting new research that reveals how this diet alters gut microbiota and affects bile acid levels, leading to reduced calorie absorption and potential therapeutic targets for obesity [6][15]. Group 1: Mechanisms of Ketogenic Diet - Traditional views suggest that the ketogenic diet induces ketone body production, prompting the body to use fat as an energy source. However, recent studies indicate that the weight loss mechanisms are more complex, including a significant increase in energy expenditure [7]. - Research from Fudan University reveals that the ketogenic diet alters specific gut microbiota, reducing bile salt hydrolase (BSH) levels, which leads to increased levels of taurodeoxycholic acid (TDCA) and taurocholic acid (TUDCA) in the bloodstream. These substances inhibit intestinal carbonic anhydrase 1 expression, directly blocking calorie absorption [7][11]. - A targeted metabolomics analysis of mice on a high-fat ketogenic diet showed a significant reduction in body weight and fasting blood glucose, with 22 metabolites elevated, including six bile acids. Notably, TDCA and TUDCA were found to play crucial roles in the weight loss mechanism [11][12]. Group 2: Clinical Observations and Implications - A clinical study involving over 400 participants confirmed that low plasma levels of TDCA and TUDCA correlate with high BMI and fasting blood glucose levels. Participants on a 12-week ketogenic diet lost an average of 5.27 kg, with significant increases in TDCA and TUDCA levels, aligning with findings from mouse experiments [8][14]. - The research supports the potential of TDCA and TUDCA as therapeutic targets for obesity and related metabolic diseases, providing a new perspective on the mechanisms of weight loss through the ketogenic diet [15]. - Further analysis of the gut environment in mice confirmed that changes in TDCA and TUDCA levels are closely related to gut microbiota, with gut microbiota transplants from ketogenic diet mice to recipient mice also resulting in weight loss [16].

Core Viewpoint - The ketogenic diet (KD) may serve as a potential strategy for treating gliomas by promoting the production of butyrate from gut microbiota, which inhibits glioma progression [4][9]. Group 1: Research Findings - Glioma patients exhibit unique gut microbiota characteristics, specifically a reduction in butyrate-producing bacteria, particularly Roseburia faecis, and lower butyrate levels [6][7]. - KD reshapes the gut microbiota in a mucin-2 dependent manner, enriching Akkermansia muciniphila (AKK) and increasing butyrate production, which activates caspase-3 in microglia, promoting an anti-tumor phenotype [6][7]. - The anti-glioma effects of KD significantly diminish under antibiotic treatment, germ-free conditions, or specific depletion of mucin-2, microglia, or caspase-3 in microglia [6][7]. Group 2: Implications for Treatment - Targeting gut microbiota or supplementing butyrate through KD may represent an effective strategy for glioma treatment [9].

Core Viewpoint - The article discusses the impact of sugar consumption on health, emphasizing the need for sugar control as a central trend in modern dietary practices. It highlights the potential risks associated with strict sugar restriction and the effects of different dietary approaches on weight loss and metabolic health [6][8][21]. Summary by Sections Sugar Consumption and Health - Sugar, particularly free sugars, is linked to increased caloric intake and various health issues such as obesity and metabolic disorders. Keeping free sugar intake below 5% of total daily calories can help reduce caloric intake by approximately 100 kilocalories [7][8]. Dietary Approaches and Clinical Trials - A recent clinical trial involving 60 participants over 12 weeks compared three dietary groups: a normal sugar intake group (MODSUG), a reduced free sugar group (LOWSUG), and a strict low-carbohydrate ketogenic group (LOWCHO). Both LOWSUG and LOWCHO groups showed significant weight loss, but the LOWCHO group experienced adverse changes in glucose tolerance and lipid profiles [9][15][16]. Metabolic and Microbiome Changes - The LOWCHO group exhibited a significant decrease in glucose tolerance and an increase in various low-density lipoprotein (LDL) particles, while high-density lipoprotein (HDL) levels decreased. Additionally, the gut microbiome diversity was notably altered, with a decrease in beneficial Bifidobacteria, which could lead to digestive health issues [18][20]. Long-term Health Implications - The article warns that while weight loss can be beneficial for heart health, the ketogenic diet may not improve cardiovascular health due to negative changes in sugar and fat metabolism. It suggests that simply controlling free sugar intake might be a more prudent approach for cardiovascular health [21].

Core Viewpoint - The article discusses the health implications of sugar consumption and dietary trends, particularly focusing on the effects of sugar intake and ketogenic diets on weight loss and metabolic health [6][8][21]. Summary by Sections Sugar Consumption and Health - Sugar, particularly free sugars, is linked to increased caloric intake and various health issues such as obesity and metabolic disorders. Reducing free sugar intake to below 5% of total daily calories could lead to a decrease of approximately 100 kilocalories in daily consumption [7][8]. - The article emphasizes that controlling sugar intake has become a central trend in modern dietary practices [8]. Ketogenic Diet Findings - A recent clinical trial involving 60 participants over 12 weeks revealed that while ketogenic diets effectively promote fat loss, they also pose potential health risks, including increased levels of "bad cholesterol" (LDL) and worsened glucose tolerance [9][10]. - The study included three dietary groups: a control group with normal sugar intake, a group with restricted free sugar intake, and a strict low-carbohydrate ketogenic group. Both the low sugar and ketogenic groups showed significant weight loss [12][15]. Metabolic and Microbiome Changes - The ketogenic group exhibited a significant decline in glucose tolerance and an increase in various low-density lipoprotein (LDL) particles, while high-density lipoprotein (HDL) levels decreased [16][20]. - Changes in gut microbiota were also noted, with a significant reduction in beneficial Bifidobacteria in the ketogenic group, which could increase the risk of digestive issues and infections [18][20]. Long-term Health Implications - The article warns that the long-term effects of ketogenic diets may include adverse changes in sugar and fat metabolism, which are associated with increased mortality risk even within "healthy" ranges of blood sugar and cholesterol levels [20]. - It suggests that while weight loss can benefit heart health, achieving this through a ketogenic diet may not be the best approach. Instead, simply controlling free sugar intake might be a more prudent choice for cardiovascular health [21].

Core Viewpoint - The emergence of drug-resistant malaria parasites necessitates the development of new treatment strategies, with a focus on dietary and metabolic interventions to combat malaria infection [2][4]. Group 1: Research Findings - A study published by a team from Shenyang Agricultural University indicates that a ketogenic diet can inhibit the growth of Plasmodium falciparum and confer protection against malaria in mice [3][4]. - The mechanism involves β-hydroxybutyrate (β-OHB), a ketone body produced during a ketogenic diet, which halts the development of malaria parasites, highlighting the potential of dietary strategies in malaria prevention [4][9]. - The study found that high levels of β-OHB in the blood disrupt the biological regulation mechanisms of malaria parasites, leading to their developmental stasis [9][11]. Group 2: Mechanisms of Action - β-OHB not only serves as an energy source but also acts as a signaling molecule that influences metabolic regulation, inflammation, and oxidative stress pathways [8]. - The inhibition of histone deacetylase (HDAC) by β-OHB results in increased histone acetylation levels, which can lead to gene expression alterations and protective effects against oxidative stress in mouse tissues [8][9]. - The research demonstrated that both ketogenic diets and direct supplementation of β-OHB can induce metabolic reprogramming in malaria parasites, reducing their NAD levels and downregulating genes associated with their development and virulence [11]. Group 3: Implications for Malaria Treatment - The findings suggest that dietary and metabolic interventions, particularly through ketogenic diets and β-OHB, could be promising strategies for developing new anti-malarial treatments [4][11]. - The study emphasizes the antimicrobial potential of metabolic interventions, as highlighted in a concurrent article in Nature Metabolism, which discusses the protective effects of β-OHB against malaria [11].