A ketogenic diet nutritional composition and uses thereof

Abstract

The application belongs to the technical field of biological medicine, and particularly relates to a ketogenic diet nutritional composition and application thereof. The ketogenic diet nutritional composition comprises, in mass parts, 60-70 parts of complex fatty acids, 5-10 parts of complex protein polypeptides, 15-20 parts of dietary fiber, 3 parts of complex vitamins and minerals, and 0-5 parts of carbohydrates. The components in the ketogenic diet nutritional composition can be used synergistically for weight loss, improvement of insulin resistance, and relief of depression or anxiety-like behavior. The results of the examples show that the ketogenic diet nutritional composition exhibits multiple benefits in overweight or obese patients with mood disorders, such as relief of depression and anxiety symptoms, stable mood, significant reduction of body weight and waist circumference, light body, optimization of metabolic indicators such as blood lipids and insulin, reduction of cardiovascular risk, long-term stable cognitive function, and good overall quality of life.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to a ketogenic diet nutritional composition and its application. Background Technology

[0002] Depressive disorders, anxiety disorders, and bipolar disorder are increasingly serious public health problems worldwide. Taking depression as an example, according to the World Health Organization's (WHO) 2024 Global Burden of Disease data, an estimated 332 million people worldwide suffer from depression, with a high proportion of overweight or obese patients, which may be related to chronic inflammation, hormonal changes, and the side effects of antidepressants. Although current drug and psychotherapy treatments provide some relief, limited efficacy and high relapse rates remain prominent issues.

[0003] The ketogenic diet is a high-fat, very low-carbohydrate, and moderate-protein dietary pattern that mimics metabolic adaptation under fasting conditions by inducing the liver to produce ketone bodies (mainly β-hydroxybutyrate, acetone, and acetoacetic acid). Therefore, developing a ketogenic combination that can effectively control weight and alleviate depressive and anxiety-like behaviors has significant application value and market potential. Summary of the Invention

[0004] The purpose of this invention is to provide a ketogenic diet nutritional composition and its application. The ketogenic diet nutritional composition of this invention can be used for weight loss, improving insulin resistance, and alleviating depressive or anxiety-like behaviors.

[0005] This invention provides a ketogenic diet nutritional composition, which, by weight, comprises 60-70 parts of complex fatty acids, 5-10 parts of complex protein peptides, 15-20 parts of dietary fiber, 3 parts of complex vitamins and minerals, and 0-5 parts of carbohydrates.

[0006] As a preferred embodiment, the mass ratio of long-chain fatty acids to medium-chain fatty acids in the complex fatty acids is 1~3:1; the mass ratio of unsaturated fatty acids to saturated fatty acids is 1~3:1; the mass ratio of monounsaturated fatty acids to polyunsaturated fatty acids is 4~8:1; and the mass ratio of Ω-6 polyunsaturated fatty acids to Ω-3 polyunsaturated fatty acids is 0.9~3:1.

[0007] As a preferred embodiment, the raw materials for preparing the complex fatty acids include at least one of coconut oil, palm oil, flaxseed oil, DHA algal oil, sacha inchi oil, camellia oil, maple seed oil, saxifrage oil, high oleic sunflower seed oil, tomato seed oil, and sea buckthorn seed oil.

[0008] As a preferred embodiment, the composite protein polypeptide includes polypeptide 1, polypeptide 2, polypeptide 3 and polypeptide 4; The amino acid sequences of polypeptides 1 to 4 are shown in SEQ ID NO. 1 to 4.

[0009] As a preferred embodiment, the mass percentage of polypeptide 1 to polypeptide 4 in the complex protein polypeptide is 0.20% to 1.00%.

[0010] As a preferred embodiment, the raw materials for preparing the complex protein polypeptide include at least one of legumes, grains, dairy products, eggs, nuts, aquatic products, and algae.

[0011] As a preferred embodiment, the total sugar content in the carbohydrate is ≤0.5%.

[0012] As a preferred embodiment, the multivitamin and mineral complex includes vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B2, vitamin B6, and vitamin B6. 12 Niacin, folic acid, pantothenic acid, calcium, potassium, magnesium, iron, and zinc.

[0013] The present invention also provides the application of the ketogenic diet nutritional composition described above in the preparation of products, including food and / or health products.

[0014] The present invention also provides the use of the ketogenic diet nutritional composition described above in the preparation of a medicament for treating depression and / or anxiety.

[0015] Beneficial Effects: This invention provides a ketogenic diet nutritional composition, comprising, by weight, 60-70 parts of complex fatty acids, 5-10 parts of complex protein peptides, 15-20 parts of dietary fiber, 3 parts of complex vitamins and minerals, and 0-5 parts of carbohydrates. The ketogenic diet nutritional composition of this invention has the highest content of complex fatty acids. Since the body uses complex fatty acids as its primary energy source, ketone bodies are produced. The complex protein peptides provide essential amino acids and are easily absorbed. The components work synergistically to aid in weight loss, improve insulin resistance, and alleviate depressive or anxiety-like behaviors. Results from the examples show that the ketogenic diet nutritional composition of this invention exhibits multiple benefits in overweight or obese patients with mood disorders, including significant relief of anxiety and partial reduction of depression; significant decreases in weight and waist circumference, resulting in a lighter physique; optimized metabolic indicators such as blood lipids and insulin; reduced cardiovascular risk; long-term stable cognitive function; and a good overall quality of life. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the embodiments will be briefly described below.

[0017] Figure 1The results represent the physiological parameters of mice; where A is body weight; B is insulin resistance; C is fasting blood glucose; D is triglyceride; E is low-density lipoprotein cholesterol; and F is high-density lipoprotein cholesterol. Figure 2 The results represent behavioral indicators in mice; where A represents the tail suspension test result; B represents the forced swimming test result; C represents the open field test result; D represents the elevated cross maze test result; E represents the sucrose preference test result; and F represents the behavioral recovery result. Figure 3 These are the results of human trials; the top image shows the ketone body results; the bottom image shows the body weight results. Figure 4 These are the results of human trials; the top image shows the BMI results; the bottom image shows the waist and abdominal circumference results. Figure 5 These are the results from human trials; the top image shows the triglyceride (TG) results; the bottom image shows the free fatty acid (FA) results. Figure 6 These are the results of human trials; the top image shows the results for free fatty acids (FFA); the bottom image shows the results for high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Figure 7 These are the results of human trials; the top image shows the sd LDL-C results; the bottom image shows the insulin level results. Figure 8 The result is for glycated hemoglobin; Figure 9 The results are the scores for the HAMD and HAMA scales. Detailed Implementation

[0018] This invention provides a ketogenic diet nutritional composition, which, by weight, comprises 60-70 parts of complex fatty acids, 5-10 parts of complex protein peptides, 15-20 parts of dietary fiber, 3 parts of complex vitamins and minerals, and 0-5 parts of carbohydrates.

[0019] Unless otherwise specified, all components involved in this invention can be obtained through conventional commercial methods.

[0020] The ketogenic diet nutritional composition of the present invention comprises 60-70 parts by weight of complex fatty acids. In specific embodiments of the present invention, the mass parts of the complex fatty acids can be any value within the range of 60-70 parts, such as 60, 61, 62, 63, 64, 65, 66, 67, 68, 69 or 70 parts.

[0021] The complex fatty acid contains long-chain fatty acids and medium-chain fatty acids. As one embodiment, the mass ratio of long-chain fatty acids to medium-chain fatty acids in the complex fatty acid can be any ratio from 1 to 3:1, for example, 1:1, 2:1, or 3:1. Long-chain fatty acids are fatty acids with more than 14 carbon atoms found in natural oils, including palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1), linoleic acid (C18:2), α-linolenic acid (C18:3), nervonic acid (docosahexaenoic acid C24:1), and docosahexaenoic acid (C22:6). Palmitic acid (C16:0) is a basic structural component of meningeal phospholipids. Membrane structures related to cell signal transduction in the human prefrontal cortex are mainly composed of palmitic acid and stearic acid. Stearic acid (C18:0) participates in the formation of 5-PAHSA, which has important neuroprotective effects; both act as structural substrates and participants in metabolic regulation. Oleic acid (C18:1, Ω-9) is a major component of meningeal phospholipids and myelin, possessing anti-inflammatory activity and reducing the risk of depressive mood. Linoleic acid (C18:2) exerts neuroprotective effects by regulating microglia differentiation and arachidonic acid metabolism. Animal experiments have shown that linoleic acid can alleviate heat-oxidized oil-induced anxiety-like behavior and depressive tendencies by upregulating CYP2J6 and LOX2S, thereby increasing the synthesis of neuroprotective lipid mediators (EETs, 9-HODE, 13-HODE). α-Linolenic acid (C18:3, ALA) intake is negatively correlated with the risk of depression: for every 0.5 g / day increase, the risk of depression decreases by 18% (RR=0.82, 95% CI: 0.71-0.94), with a stronger effect in those with lower linoleic acid intake. Nervonic acid (docosahexaenoic acid C24:1) is a very long-chain monounsaturated fatty acid and a core component of sphingomyelin, crucial for myelin formation and nerve signal transduction. Studies have shown that nervonic acid supplementation can alleviate D-galactose / aluminum chloride-induced cognitive and neurological function impairment in mice, alleviate brain, liver, and thymus atrophy, and has antioxidant and immune-enhancing effects; nervonic acid supplementation can promote myelin repair and improve memory and concentration. Docosahexaenoic acid (C22:6), or DHA, accounts for 15%–20% of the fatty acids in the cerebral cortex and is crucial for neuronal membrane fluidity and signal transduction. Meta-analyses support its benefits in major depressive disorder and bipolar disorder in affective disorders. Medium-chain fatty acids (MCFAs) are C8–12 fatty acids found in natural oils, mainly including caprylic acid (C8:0) and capric acid (C10:0). MFAs can directly enter the liver via the portal vein for rapid oxidation and energy supply, promoting ketone body production and increasing energy expenditure. MFA supplementation can improve ketogenic efficiency and enhance weight loss and metabolic improvement effects. Triglycerides are organic compounds formed by the esterification and dehydration condensation of one molecule of glycerol and three molecules of fatty acids, and are widely found in natural oils. In this invention, MFAs are provided in the form of medium-chain triglycerides.

[0022] The compound fatty acid contains unsaturated fatty acids and saturated fatty acids. As one embodiment, the mass ratio of unsaturated fatty acids to saturated fatty acids in the compound fatty acid can be any ratio between 1 and 3:1, for example, 1:1, 2:1, or 3:1. The unsaturated fatty acids (UFA) in this invention are the sum of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) in natural oils; the saturated fatty acids (SFA) are fatty acids whose molecules do not contain carbon-carbon double bonds, such as palmitic acid, stearic acid, caprylic acid, and capric acid. Appropriately increasing the proportion of unsaturated fatty acids (especially monounsaturated fatty acids and omega-3 polyunsaturated fatty acids) helps improve lipid metabolism and reduce cardiovascular risk.

[0023] The complex fatty acid contains monounsaturated fatty acids and polyunsaturated fatty acids. As one embodiment, the mass ratio of monounsaturated fatty acids to polyunsaturated fatty acids in the complex fatty acid can be any ratio between 4 and 8:1, such as 4:1, 5:1, 6:1, 7:1, or 8:1. A higher proportion of monounsaturated fatty acids (such as oleic acid and nervonic acid) helps maintain cell membrane fluidity and has anti-inflammatory effects.

[0024] The polyunsaturated fatty acids include omega-6 and omega-3 polyunsaturated fatty acids. In one embodiment, the mass ratio of omega-6 to omega-3 polyunsaturated fatty acids in the complex fatty acid mixture can be any ratio between 0.9 and 3:1, such as 0.9:1, 1:1, 2:1, or 3:1. The omega-6 polyunsaturated fatty acids in this invention include linoleic acid (C18:2); the omega-3 polyunsaturated fatty acids include alpha-linolenic acid (C18:3) and docosahexaenoic acid (C22:6). An excessively high omega-6 / omega-3 ratio can exacerbate neuroinflammation and insulin resistance. The mass ratio of omega-6 to omega-3 polyunsaturated fatty acids (0.9–3:1) of this invention helps to exert the neuroprotective and anti-inflammatory effects of omega-3 fatty acids (DHA, alpha-linolenic acid).

[0025] In one embodiment, the raw materials for preparing the complex fatty acids include at least one selected from coconut oil, palm oil, flaxseed oil, DHA algal oil, sacha inchi oil, camellia oil, maple seed oil, *Xanthoceras sorbifolium* oil, high-oleic sunflower seed oil, tomato seed oil, and sea buckthorn seed oil. The coconut oil and palm oil of this invention are rich in medium-chain fatty acids (caprylic acid and capric acid); the flaxseed oil, DHA algal oil, and sacha inchi oil are rich in omega-3 polyunsaturated fatty acids; the camellia oil, maple seed oil, *Xanthoceras sorbifolium* oil, and high-oleic sunflower seed oil are rich in omega-9 monounsaturated fatty acids; the tomato seed oil is rich in omega-6 polyunsaturated fatty acids; and the sea buckthorn seed oil is rich in omega-7 monounsaturated fatty acids.

[0026] The complex fatty acids described in this invention involve multiple components and are not simply a superposition of effects. Rather, they produce a significant overall synergistic effect in the ketogenic composition through multidimensional synergistic interactions of chain length gradients, saturation ratios, and neuroactive components. Specifically, medium-chain fatty acids are rapidly oxidized in the liver to induce ketosis, while long-chain fatty acids are slowly released to provide sustained energy and serve as substrates for nerve membrane structures. The two complement each other in their absorption and metabolism sequence, synergistically prolonging the effective ketosis window. Unsaturated fatty acids are combined with saturated fatty acids in a 1-3:1 ratio, ensuring ketogenic efficiency while using Ω-3 and Ω-9 fatty acids to regulate lipid metabolism and inhibit pro-inflammatory pathways, thus mitigating the risks of high saturated fat metabolism. Nervonic acid, DHA, and α-linolenic acid further form an "energy-structure-signal" synergistic effect with ketone bodies: ketone bodies provide alternative energy, DHA and nervonic acid synergistically enhance membrane fluidity and promote myelin repair, and α-linolenic acid is metabolized to generate neuroprotective lipid mediators. The interaction of these three amplifies neuroprotective and mood homeostasis effects. Therefore, the compound fatty acid of this invention constructs a synergistic gain network of "rapid energy supply - continuous ketogenesis - structural repair - anti-inflammatory homeostasis", and its overall technical effect is significantly better than the sum of the independent effects of each individual component.

[0027] The ketogenic diet nutritional composition of the present invention comprises 5-10 parts by weight of a complex protein polypeptide. In specific embodiments of the present invention, the mass fraction of the complex protein polypeptide can be any value from 5 to 10 parts, for example, 5, 6, 7, 8, 9, or 10 parts. As one embodiment, the complex protein polypeptide comprises polypeptide 1, polypeptide 2, polypeptide 3, and polypeptide 4; as one embodiment, the amino acid sequence of polypeptide 1 is as shown in SEQ ID NO.1: EREEDEEQVDEEWRGS; as one embodiment, the amino acid sequence of polypeptide 2 is as shown in SEQ ID NO.2: WEREEDEEQVDEEWRGS; as one embodiment, the amino acid sequence of polypeptide 3 is as shown in SEQ ID NO.3: EREEDEEQVDEEWRGSQ; as one embodiment, the amino acid sequence of polypeptide 4 is as shown in SEQ ID NO.4: WEREEDEEQVDEE.

[0028] In one embodiment, the mass percentage of polypeptides 1 to 4 in the composite protein polypeptide can be any value between 0.20% and 1.00%, for example, 0.20%, 0.30%, 0.35%, 0.39%, 0.40%, 0.50%, 0.55%, 0.60%, 0.66%, 0.70%, 0.77%, 0.80%, 0.84%, 0.90%, 0.93%, or 1.00%. In a specific embodiment of the present invention, the mass percentage of the composite protein polypeptide is 0.39%; wherein the mass percentage of polypeptide 1 in the composite protein polypeptide is 0.12%; the mass percentage of polypeptide 2 in the composite protein polypeptide is 0.11%; the mass percentage of polypeptide 3 in the composite protein polypeptide is 0.12%; and the mass percentage of polypeptide 4 in the composite protein polypeptide is 0.04%.

[0029] The complex protein peptides described in this invention are rich in glutamate and tryptophan. Glutamate is a major excitatory neurotransmitter in the brain, participating in nerve signal transmission, learning and memory, and mood regulation. In a state of anxiety, the level of glutamate or the activity of its receptors in specific brain regions (such as the hippocampus and prefrontal cortex) may be abnormal. Tryptophan is the only raw material for synthesizing serotonin (5-hydroxytryptamine), which is crucial for mood stability, sleep, and social behavior. Insufficient serotonin levels are often associated with mood disorders such as anxiety and depression. The addition of complex protein peptides rich in glutamate and tryptophan in this invention helps alleviate anxiety and depression.

[0030] As one embodiment, the preparation of the composite protein polypeptide includes the following steps: mixing the raw materials and water, extracting the protein under alkaline conditions, centrifuging and collecting the supernatant, adjusting the pH to the isoelectric point of the protein to precipitate the protein, and collecting the precipitate through solid-liquid separation; resuspending the precipitate to obtain a protein suspension; adding a protease to the protein suspension for enzymatic hydrolysis to obtain an enzymatic hydrolysate; and separating and purifying the enzymatic hydrolysate to obtain the composite protein polypeptide.

[0031] In one embodiment, the raw materials for preparing the complex protein polypeptide include at least one selected from legumes, grains, dairy products, eggs, nuts, aquatic products, and algae; more preferably, dairy products. In one embodiment, the dairy products include at least one selected from skim milk powder, whey powder, and whey protein powder; in another embodiment, the source of the dairy products includes at least one selected from bovine, sheep, and camel sources. In a specific embodiment of the present invention, skim milk powder is used as a raw material to prepare the complex protein polypeptide. Skim milk powder is merely an exemplary raw material and does not limit the scope of protection of the present invention.

[0032] In one embodiment, the present invention involves pulverizing and sieving the raw materials to obtain sieved raw materials. In one embodiment, the sieve mesh size is 60 mesh.

[0033] This invention involves mixing the sieved raw material with water to obtain a mixture. In one embodiment, the mass-to-volume ratio of the sieved raw material to water is 1:20. The mixture is then used to extract protein under alkaline conditions to obtain a protein extract. In one embodiment, the alkaline conditions are adjusted using NaOH; the pH value of the alkaline conditions is 10.0 ± 0.1. In another embodiment, the extraction is a stirred extraction; the stirring speed is 60-100 r / min; and the extraction time is 60 min.

[0034] After obtaining the protein extract, the present invention centrifuges the protein extract and collects the supernatant. In one embodiment, the centrifugation time is 15 minutes, and the centrifugation speed is 1000 r / min.

[0035] After obtaining the supernatant, the present invention adjusts the pH of the supernatant to the isoelectric point of the protein to precipitate the protein. As one embodiment, adjusting the pH to the isoelectric point of the protein includes: adjusting the pH to 4.5 ± 0.1 using hydrochloric acid, and flocculating for 10-20 minutes until the system is stable. The system described in this invention is stable, microprecipitates are completely formed, and there is a clear boundary between the precipitate and the supernatant.

[0036] This invention involves solid-liquid separation to collect the precipitate after protein precipitation; as one embodiment, the solid-liquid separation includes centrifugation; the centrifugation time is 15 min; and the centrifugation speed is 1000 r / min.

[0037] The present invention involves washing and resuspending the precipitate to obtain a protein suspension. As one embodiment, the washing is performed 1-2 times; the washing solvent is deionized water.

[0038] After obtaining the protein suspension, the present invention adjusts the protein suspension to a pH of 7.5-8.0 to obtain a slurry-adjusted protein suspension. As one embodiment, the present invention uses an alkaline buffer solution to adjust the protein suspension. As one embodiment, the mass percentage concentration of protein in the slurry-adjusted protein suspension can be 8%-15%, for example, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15%.

[0039] The protein suspension after slurry preparation is obtained. In this invention, a protease is added to the slurry for enzymatic hydrolysis to obtain an enzymatic hydrolysate. As one embodiment, the protease includes trypsin, papain, and alkaline protease. As one embodiment, based on the mass of the slurry-prepared protein suspension, the amount of trypsin added is 1% (w / w); the amount of papain added is 0.2% (w / w); and the amount of alkaline protease added is 0.3% (w / w). As one embodiment, the enzyme activity of the trypsin can be 1800~2000 U / g, for example, 1800, 1900, or 2000 U / g; the enzyme activity of the papain can be 1800~2000 U / g, for example, 1800, 1900, or 2000 U / g; and the enzyme activity of the alkaline protease can be 1800~2000 U / g, for example, 1800, 1900, or 2000 U / g. In one embodiment, the enzymatic hydrolysis temperature is 50~55℃; the enzymatic hydrolysis time is 4h.

[0040] After obtaining the enzymatic hydrolysate, the process further includes enzyme inactivation. As one embodiment, the enzyme inactivation temperature is 115-120°C, and the enzyme inactivation time is 30 minutes.

[0041] This invention separates and purifies the enzyme hydrolysate after enzyme inactivation to obtain the complex polypeptide. As one embodiment, the separation and purification includes filtration. As one embodiment, the filtration uses an ultrafiltration membrane with a molecular weight cutoff of 10 kDa. This invention uses a 10 kDa ultrafiltration membrane to remove polypeptides with a molecular weight cutoff exceeding 10 kDa, and the permeate is then treated with a nanofiltration membrane to remove free amino acids, and the nanofiltration retentate is collected.

[0042] This invention sterilizes and dries filtered polypeptides to obtain dried composite protein polypeptides. As one embodiment, the sterilization is instantaneous sterilization at 130-135°C. As another embodiment, the drying includes spray drying; the inlet temperature of the spray dryer is 170°C and the outlet temperature is 80°C.

[0043] The ketogenic diet nutritional composition of the present invention comprises 15-20 parts by weight of dietary fiber. In specific embodiments of the present invention, the weight of the dietary fiber can be any value within the range of 15-20 parts, for example, 15, 16, 17, 18, 19, or 20 parts. As one embodiment, the dietary fiber comprises at least one of resistant dextrin, gum arabic, fructooligosaccharides, and galactooligosaccharides. Dietary fiber is fermented by intestinal flora to produce short-chain fatty acids (SCFAs) such as butyric acid, propionic acid, and acetic acid, which mediate the gut-brain axis and simultaneously achieve metabolic remodeling (weight loss, lipid reduction, and improvement of insulin resistance) and mood regulation (reducing cortisol, promoting 5-HT / BDNF, and inhibiting neuroinflammation).

[0044] The ketogenic diet nutritional composition of the present invention comprises 3 parts by weight of a complex vitamin and mineral. As one embodiment, the complex vitamin and mineral includes vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, niacin, folic acid, pantothenic acid, calcium, potassium, magnesium, iron, and zinc. In a specific embodiment of the present invention, the complex vitamin and mineral, per 100 g, comprises vitamin A 421 μg RE, vitamin D 1.4 μg, vitamin E 6.8 mg α-TE, vitamin B1 1.15 mg, vitamin B2 1.15 mg, vitamin B6 0.97 mg, vitamin B12 1.22 μg, niacin 13.34 mg, folic acid 136 μg DFE, pantothenic acid 2.92 mg, calcium 400 mg, potassium 400 mg, magnesium 158 mg, iron 12.5 mg, and zinc 9 mg.

[0045] The ketogenic diet nutritional composition of the present invention comprises 0 to 5 parts by weight of carbohydrates. In specific embodiments of the present invention, the mass parts of carbohydrates can be any value from 0 to 5 parts, for example 0, 1, 1.5, 2, 3, 4, or 5 parts. As one embodiment, the total sugar content in the carbohydrates is ≤0.5%. As one embodiment, the total sugar is calculated as the sum of fructose, glucose, sucrose, maltose, and lactose.

[0046] In one embodiment, the ketogenic diet nutritional composition, by percentage, comprises 60%–70% complex fatty acids, 5%–10% complex protein peptides, 15%–20% dietary fiber, 3% various vitamins and minerals, ≤5% carbohydrates (of which total sugar ≤0.5%), ≤7% moisture, and ≤7% ash. In a specific embodiment of the present invention, the ketogenic diet nutritional composition, by percentage, comprises 65% complex fatty acids, 5% complex protein peptides, 18% dietary fiber, 3% various vitamins and minerals, 2.5% carbohydrates (of which total sugar ≤0.5%), 4% moisture, and 2.5% ash. This invention also provides the application of the ketogenic diet nutritional composition described above in the preparation of products, including food and / or health supplements. The food described in this invention can be used by overweight and / or obese individuals to improve insulin resistance and promote weight loss; the health supplement described in this invention can be used to improve sleep. As one embodiment, the products are suitable for patients with overweight and / or obese mood disorders.

[0047] The present invention also provides the use of the ketogenic diet nutritional composition described above in the preparation of a medicament for treating depression and / or anxiety. As one embodiment, the medicament functions to include at least one of the following: (1) alleviating anxiety-like behaviors; (2) alleviating depression-like behaviors; and (3) improving sleep.

[0048] As one implementation, the product has at least one of the following functions: (1) improving insulin resistance; (2) weight loss; (3) alleviating anxiety-like behavior; (4) alleviating depression-like behavior; (5) improving metabolism; and (6) improving sleep.

[0049] To further illustrate the present invention, the technical solutions provided by the present invention will be described in detail below with reference to the accompanying drawings and embodiments, but these should not be construed as limiting the scope of protection of the present invention.

[0050] Example 1 A ketogenic diet nutritional composition, by weight percentage, comprises: 65% complex fatty acids, 5% complex protein peptides, 18% dietary fiber, 3% various vitamins and minerals, 2.5% carbohydrates (of which total sugar ≤0.5%), 4% moisture, and 2.5% ash.

[0051] The complex fatty acids are prepared using molecular distillation. Coconut oil, palm oil, flaxseed oil, DHA algal oil, sacha inchi oil, camellia oil, maple seed oil, *Sapindus mukorossi* oil, high-oleic sunflower seed oil, tomato seed oil, and sea buckthorn seed oil were used as raw materials. These raw materials were refined to obtain refined raw materials, which were then separated and enriched using a scraped-film molecular distillation apparatus to concentrate the desired fatty acids. For example, coconut oil was refined to obtain refined coconut oil, which was then separated and enriched using a scraped-film molecular distillation apparatus to obtain coconut oil rich in medium-chain triglycerides. During the separation process, the system pressure of the scraped-film molecular distillation apparatus was 0.10 Pa to 0.11 Pa, the distillation temperature was 110℃ to 115℃, the feed temperature was 60℃, the feed rate was 25 mL / h to 40 mL / h, and the scraper rotation speed was 300 r / min.

[0052] After the above processing, coconut oil rich in medium-chain triglycerides, palm oil rich in medium-chain triglycerides, flaxseed oil rich in omega-3 polyunsaturated fatty acids, DHA algal oil rich in omega-3 polyunsaturated fatty acids, sacha inchi oil rich in omega-3 polyunsaturated fatty acids, camellia oil rich in omega-9 monounsaturated fatty acids, maple seed oil rich in omega-9 monounsaturated fatty acids, saxifrage seed oil rich in omega-9 monounsaturated fatty acids, high-oleic sunflower seed oil rich in omega-9 monounsaturated fatty acids, tomato seed oil rich in omega-6 polyunsaturated fatty acids, and sea buckthorn seed oil rich in omega-7 monounsaturated fatty acids were obtained respectively.

[0053] The coconut oil and palm oil rich in medium-chain triglycerides prepared above, flaxseed oil, DHA algal oil, and sacha inchi oil rich in Ω3 polyunsaturated fatty acids, camellia oil, maple seed oil, saxifrage oil, and high-oleic sunflower seed oil rich in Ω9 monounsaturated fatty acids, tomato seed oil rich in Ω6 polyunsaturated fatty acids, and sea buckthorn seed oil rich in Ω7 monounsaturated fatty acids are then mixed. The resulting complex fatty acid composition has a long-chain fatty acid to medium-chain fatty acid ratio of 1~3:1; an unsaturated fatty acid to saturated fatty acid ratio of 1~3:1; a monounsaturated fatty acid to polyunsaturated fatty acid ratio of 4~8:1; and an Ω-6 to Ω-3 polyunsaturated fatty acid ratio of 0.9~3:1.

[0054] Preparation of complex protein peptides: (1) Protein Extraction: Bovine skim milk powder was pulverized, passed through a 60-mesh sieve, and 20 times its volume of deionized water was added. The mixture was thoroughly mixed, and the pH was adjusted to 10.0 (±0.1) with an appropriate amount of NaOH. The mixture was continuously stirred and extracted for 60 min, followed by centrifugation for 15 min. The supernatant was taken and the pH was adjusted to 4.5 (±0.1) with an appropriate amount of hydrochloric acid. The mixture was quickly mixed and flocculated for 10-20 min until the system was stable (the precipitate was completely formed, and there was a clear boundary between the precipitate and the supernatant). The mixture was centrifuged for 15 min. The precipitate was washed 1-2 times with an appropriate amount of deionized water, and then resuspended with an appropriate amount of deionized water to obtain a protein suspension.

[0055] (2) Enzymatic hydrolysis: The protein suspension was prepared at pH 7.5-8.0, and 1% trypsin, 0.2% papain and 0.3% alkaline protease were added by mass percentage; the mixture was then hydrolyzed at 50-55℃ for 4 hours. After hydrolysis, the mixture was heated to 115-120℃ to inactivate the enzyme, resulting in a hydrolyzed small molecule protein solution.

[0056] (3) Purification: Ultrafiltration membrane with a molecular weight cutoff of 10 kDa is used to remove peptides with a molecular weight cutoff of more than 10 kDa. The permeate is then removed by nanofiltration membrane to remove free amino acids. The nanofiltration retentate is collected and sterilized at 130~135℃. Finally, spray drying is carried out at an inlet temperature of 170℃ and an outlet temperature of 80℃ to obtain hydrolyzed small molecule protein powder, i.e., complex protein peptides.

[0057] Based on mass percentage, the content of polypeptide 1 (SEQ ID NO.1) in the obtained complex protein polypeptide is 0.12%; the content of polypeptide 2 (SEQ ID NO.2) is 0.11%; the content of polypeptide 3 (SEQ ID NO.3) is 0.12%; and the content of polypeptide 4 (SEQ ID NO.4) is 0.04%.

[0058] Comparative Example 1 A ketogenic diet nutritional composition, with the same components as in Example 1, except that the complex fatty acids do not contain medium-chain fatty acids, that is, coconut oil rich in medium-chain triglycerides and palm oil rich in medium-chain triglycerides are omitted.

[0059] Comparative Example 2 A ketogenic diet nutritional composition, with the same components as in Example 1, except that the mass ratio of unsaturated fatty acids to saturated fatty acids in the complex fatty acids is 0.5~0.9:1.

[0060] Comparative Example 3 A ketogenic diet nutritional composition, with the same components as in Example 1, except that the mass ratio of monounsaturated fatty acids to polyunsaturated fatty acids in the complex fatty acids is 1~3:1.

[0061] Comparative Example 4 A ketogenic diet nutritional composition, with the same components as in Example 1, except that the mass ratio of Ω-6 and Ω-3 polyunsaturated fatty acids in the complex fatty acids is 4~10:1.

[0062] Example 2 Seventy 6-week-old SPF-grade male C57BL / 6J mice, weighing 18-22 g, were housed in an SPF-grade animal room at a temperature of 22±2℃ and a humidity of 50±10%, with a 12-h light-dark cycle and free access to food and water.

[0063] After inducing obesity in the mice by a high-fat diet (HFD, 60% fat as the energy source) for 8 weeks, they were randomly divided into 7 groups (n=10 / group), as follows: Normal diet control group (NC): Mice were fed a standard maintenance diet (10% fat energy) at a dose of 5g / 100g / day for a total of 4 weeks.

[0064] High-fat diet sustained group (HFD): Mice were fed a high-fat diet (60% fat energy) at a dose of 5g / 100g / day for a total of 4 weeks.

[0065] Ketogenic diet intervention group A: Mice were fed the ketogenic diet nutritional composition prepared in Example 1 at a dose of 5g / 100g / day based on body weight for a total of 4 weeks.

[0066] Group B of ketogenic diet intervention: Mice were fed the ketogenic diet nutritional composition prepared in Comparative Example 1 at a dose of 5g / 100g / day based on body weight for a total of 4 weeks.

[0067] Ketogenic diet intervention group C: Mice were fed the ketogenic diet nutritional composition prepared in Comparative Example 2 at a dose of 5g / 100g / day based on body weight for a total of 4 weeks.

[0068] Ketogenic diet intervention group D: Mice were fed the ketogenic diet nutritional composition prepared in Comparative Example 3 at a dose of 5g / 100g / day based on body weight for a total of 4 weeks.

[0069] Ketogenic diet intervention group E: Mice were fed the ketogenic diet nutritional composition prepared in Comparative Example 4 at a dose of 5g / 100g / day based on body weight for a total of 4 weeks.

[0070] Weight and food intake were recorded weekly. After 4 weeks of intervention, mice were fasted for 12 hours, and blood samples were collected for behavioral tests. Changes in body weight, fasting blood glucose (FBG), fasting insulin (FINS), HOMA-IR index, and lipid profiles (triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)) were measured in each group. Depressive and anxiety-like behaviors were assessed using the suspended tail test (TST), forced swimming test (FST), open field test (OF), elevated cross maze (EPM), and sucrose preference test (SPT). The suspended tail test, forced swimming test, and sucrose preference test were used to assess depressive-like behaviors, while the open field test and elevated cross maze were used to assess anxiety-like behaviors.

[0071] Fasting blood glucose was measured using the glucose oxidase method, fasting insulin was measured using ELISA, and the insulin resistance index was calculated according to formula (1); the lipid profile was measured using a fully automated biochemical analyzer.

[0072] The insulin resistance index HOMA-IR = FBG (mmol / L) × FINS (μIU / mL) / 22.5.

[0073] Tail suspension test (TST), total duration 6 min, recording the immobility time for the last 4 min; Forced swimming test (FST), total duration 6 min, recording the immobility time for the last 4 min; Open field test (OF), recording the time spent in the central area for 5 min; Elevated cross maze test (EPM), recording the time spent in the open arm for 5 min; Sugar water preference test (SPT), calculating the sugar water preference rate using the 24-hour two-bottle method.

[0074] Statistical analysis was performed using SPSS 26.0 software. Quantitative data were expressed as Mean ± SD. One-way ANOVA was used for comparisons among multiple groups, and Tukey's HSD test (for homogeneity of variance) or Games-Howell's test (for unequal variances) was used for pairwise comparisons between groups. P < 0.05 was considered statistically significant. The results are shown in Tables 1 and 2.

[0075] Table 1 Summary of experimental indicators for each group (Mean±SD, n=10)

[0076] Table 2. Significant differences between Group A and other groups

[0077] Note: Comparison between Group A and HFD Group: This indicates that P < 0.05. This indicates that P < 0.01. The symbol indicates P < 0.001; Comparing group A with groups B through E: # indicates P < 0.05, ## indicates P < 0.01 After 4 weeks of intervention, the changes in body weight of mice in each group were as follows: Figure 1 As shown in Figure A, compared with the HFD group (+2.50±0.65g), all ketogenic diet intervention groups showed significant weight reduction (P<0.001). Group A showed the most significant weight reduction (-6.80±0.92g), significantly better than groups B (-5.20±1.05g, P<0.05), C (-4.50±0.98g, P<0.01), D (-5.00±1.20g, P<0.05), and E (-4.00±1.10g, P<0.01). The results indicate that formula A containing MCT had the best weight loss effect, while removing MCT (group B) or changing the fatty acid ratio (group CE) significantly weakened the weight loss effect.

[0078] Insulin resistance and glucose metabolism outcomes Figure 1 As shown in Figures B-C. Compared with the HFD group, FBG and HOMA-IR were significantly reduced in all intervention groups (P<0.001). Group A had significantly lower HOMA-IR (4.33±0.35) and FBG (6.50±0.48 mmol / L) than other intervention groups (P<0.01 or P<0.05), and was close to the levels of the NC group. Group B had significantly higher HOMA-IR (8.02±0.62) and FBG (8.20±0.72 mmol / L) than Group A (P<0.01), indicating that MCT plays a key role in improving insulin sensitivity. Group E had the highest HOMA-IR (9.58±0.78), suggesting that a high Ω6:Ω3 ratio may exacerbate insulin resistance.

[0079] Lipid profile results as follows Figure 1 As shown in Figures D-F. The results indicate that group A showed the most comprehensive improvement in lipid profile ( Figure 1In the D-F group: TG (1.05±0.18mmol / L) and LDL-C (1.35±0.12mmol / L) were significantly lower than those in other intervention groups (P<0.01), while HDL-C (1.15±0.09mmol / L) was significantly higher than those in other intervention groups (P<0.01), and all indicators were close to the levels in the NC group.

[0080] Results of depressive-like behaviors (tail suspension test, forced swimming test, and sucrose preference test) are as follows Figure 2 As shown in Figures A, B, and E. Compared with the HFD group, the immobility times for both TST and FST were significantly shorter in all intervention groups (P<0.01). The immobility times for TST (105.0±8.5s) and FST (115.0±10.2s) in group A were significantly shorter than those in groups B through E (P<0.05), and approached the levels of the NC group, indicating that group A exhibited the mildest depressive-like behavior. (Saccharide preference test) Figure 2 The results showed that the sugar water preference rate in group A (72.0±6.5%) was significantly higher than that in group BE (P<0.05) and close to that in group NC (78.0±5.2%), further confirming that group A had the strongest effect on improving anhedonia.

[0081] The results of the open field test are as follows Figure 2 As shown in Figure C, the dwell time in the central region of group A (68.0±9.5s) was significantly longer than that of group HFD (45.0±6.8s, P<0.001) and group BE (P<0.05), and close to that of group NC (75.0±7.5s), indicating the lowest level of anxiety.

[0082] Elevated cross maze, like Figure 2 As shown in Figure D, the open-arm dwell time in group A (52.0±6.8s) was significantly higher than that in group HFD (32.0±5.5s, P<0.001) and group BE (P<0.05), further confirming the ameliorative effect of group A on anxiety-like behaviors.

[0083] This embodiment systematically compared the intervention effects of five ketogenic diet nutritional compositions with different fatty acid ratios on mice (a high-fat diet-induced obesity model, assessed by behavioral tests for depressive / anxiety-like behaviors), and added a normal diet control group (NC) and a continuous high-fat diet group (HFD) as references. The results showed that the formulation A, containing MCT and with optimized fatty acid ratios, was significantly superior to other formulations and the continuous high-fat diet in terms of weight loss, improvement of insulin resistance, regulation of blood lipids, and alleviation of depressive / anxiety-like behaviors.

[0084] Group B (without medium-chain triglycerides, MCT) was significantly weaker than Group A in both weight loss and metabolic improvement. MCT can be directly oxidized in the liver via the portal vein for energy, promoting ketone body production and increasing energy expenditure. Lack of MCT leads to decreased ketogenic efficiency, weakening the effects of weight loss and metabolic improvement. Although Group B was still superior to the HFD group in this study, the difference compared to Group A was significant, confirming the crucial role of MCT in the ketogenic diet formulation.

[0085] Group C (low U / S ratio) showed the most significant dyslipidemia, with elevated TG and LDL-C and decreased HDL-C. Appropriately increasing the proportion of unsaturated fatty acids (especially monounsaturated fatty acids and omega-3 polyunsaturated fatty acids) can help improve lipid metabolism and reduce cardiovascular risk.

[0086] Group D (low MU / PU ratio) showed effects between Group A and Group C / E. A higher proportion of monounsaturated fatty acids (such as oleic acid and nervonic acid) helps maintain cell membrane fluidity and has anti-inflammatory effects.

[0087] Group E (high Omega-6 / Omega-3 ratio) performed the worst in metabolic and behavioral indicators. An excessively high Omega-6 / Omega-3 ratio exacerbates neuroinflammation and insulin resistance. Optimizing the Omega-6 / Omega-3 ratio (0.9–3:1) helps to exert the neuroprotective and anti-inflammatory effects of Omega-3 fatty acids (DHA, alpha-linolenic acid).

[0088] The formulation in Group A contains special polypeptide sequences enriched with glutamate and tryptophan, which may exert antidepressant and anti-anxiety effects by regulating the central glutamatergic and 5-HTergic systems.

[0089] In this embodiment, the immobility time of the TST in group A was approximately 105 seconds, which is within the normal range (80-150 seconds) for C57BL / 6J mice, indicating that the intervention in group A restored the depressive-like behavior of obese mice to a near-normal level.

[0090] Example 3 This study included patients with depressive disorders or bipolar disorder who met the inclusion criteria. All participants signed informed consent forms before the start of the study. Inclusion criteria included: (1) meeting the diagnostic criteria for depressive disorders or bipolar disorder; (2) meeting the age requirements for the study; and (3) being able to understand and follow the study protocol. Exclusion criteria included severe physical illness, severe psychotic symptoms, and a history of substance dependence. A total of 53 participants were ultimately included, including 22 patients with depressive disorders and 31 patients with bipolar disorder. Each participant was assessed at multiple time points, and multiple repeated measurements were obtained in various aspects, including mood symptom scales, body composition, metabolism, and cognition.

[0091] During the experiment, all subjects received a ketogenic diet intervention while maintaining their original psychiatric medication. The ketogenic diet regimen consisted of approximately 60% high-fat, 30% protein, and 10% carbohydrates. The ketogenic diet nutritional composition prepared in Example 1 was used as the main source of nutrition, with a daily intake of 90g, which accounted for approximately 30% of the daily energy intake of adolescents or adults.

[0092] The intervention process included: a 1-week titration period, gradually increasing the ketogenic diet dose; and a 12-week stabilization period, maintaining a stable dose. During the intervention, subjects maintained their original psychiatric medication regimen.

[0093] The main observational indicators during the intervention included psychiatric symptoms, cognitive function, and metabolic indicators. Psychiatric symptoms were assessed using the following scales: depressive symptoms: Hamilton Depression Rating Scale-17 (HAMD-17); anxiety symptoms: Hamilton Anxiety Rating Scale (HAMA); manic symptoms: Young's Mania Rating Scale (YMRS); quality of life: WHOQOL-BREF (Short Version of the Quality of Life Scale) and Sheehan's Disorders Scale (SDS). Cognitive function was assessed using the THINC-it cognitive test. Metabolic indicators included: body mass index (BMI); weight; lipid profiles (HDL, LDL, TG, TC); blood glucose and other metabolic indicators; in addition, blood ketone levels were monitored to assess ketosis.

[0094] Fifteen participants withdrew midway, while the remaining participants adhered to the ketogenic diet throughout. All participants were assessed at the following time points: baseline; week 4; week 12; and follow-up period (week 16, four weeks after the end of the intervention). The day the ketogenic diet began was D1, and the baseline period was D-14 to D0 (i.e., data collected within two weeks prior to starting the ketogenic diet). The main analysis focused on the trend of changes from baseline to the intervention period. Statistical analysis was performed using SPSS software. Since the study data were repeated measures data, a linear mixed model (LMM) was used for analysis. The model was defined as follows: dependent variable: each observed indicator; fixed effects: time, gender, and age; random effects: participant ID. The repeated measures structure used an AR(1) covariance structure. The statistical significance level was set at P < 0.05.

[0095] Results data (1) Basic Information: Data on 22 indicators, including emotional symptoms, body composition, and metabolism, are shown in Table 3. Among the 22 indicators, 10 indicators generally showed a decreasing trend over time. 14 indicators showed significant differences between time points. Among them, 12 indicators showed significant changes after the intervention compared to baseline. These are: HAMA score; weight; BMI; waist circumference; abdominal circumference; free fatty acids (FA); β-hydroxybutyrate (β-HB); triglycerides (TG); small dense low-density lipoprotein cholesterol (sdLDL-C); insulin; and glycated hemoglobin.

[0096] Table 3. Significant differences in 22 indicators, including emotional symptoms, body composition, and metabolism, during the intervention process.

[0097] (2) Markers of ketosis Venous blood samples were collected from subjects at baseline and at weeks 4, 12, and 16 of ketosis to measure β-hydroxybutyrate (β-HB) levels. Results are as follows: Figure 3 As shown in the upper figure, β-hydroxybutyrate (β-HB), an objective indicator of ketogenic diet adherence, significantly increased from baseline at 4 and 12 weeks post-intervention. Compared to baseline, β-HB increased by an average of 689.09 μmol / L at 4 weeks post-intervention (P<0.001), and by 511.71 μmol / L at 12 weeks post-intervention (P<0.001), before gradually declining to no significant difference from baseline at 16 weeks post-intervention (mean difference -10.61, P=1.000). These results indicate that subjects successfully entered ketosis during the intervention, synchronized with the dietary intervention, and gradually decreased after the intervention ended.

[0098] (3) Changes in weight and body composition After 12 weeks of ketogenic diet intervention, several metabolic indicators of the subjects changed significantly. Weight showed a significant decreasing trend during the intervention period (F=28.402, P<0.001) (Table 3). Fixed-effects modeling showed that, with time as a continuous variable, weight decreased by an average of 1.944 kg per unit of time (t=-5.329, P<0.001). Compared with baseline, participants' weight decreased significantly at all stages. Bonferroni-corrected pairwise comparisons showed that, compared with baseline, weight decreased by an average of 2.786 kg at 4 weeks post-intervention (P<0.001), further decreasing to an average of 5.735 kg at 12 weeks post-intervention (P<0.001), and remained significantly lower than baseline at 16 weeks post-intervention (mean difference -5.527, P<0.001) (see Table 3). Figure 3(See lower figure). In terms of time trend, weight showed a continuous and significant downward trend in the first 12 weeks after the intervention, with the fastest rate of weight loss in the first 4 weeks, averaging 0.7 kg per week. From weeks 4 to 12, the rate of weight loss slowed down, averaging 0.4 kg per week. However, there was no statistically significant change in weight between weeks 12 and 16 after the intervention (mean difference 0.208, P=1.000), suggesting that the weight loss peaked at week 12 after the intervention, and weight levels subsequently stabilized. Gender had a significant effect on weight (t=-5.617, P<0.001), while age had no significant effect (t=0.836, P=0.403). Among the 44 participants at 4 weeks after the intervention, all experienced weight loss (100%). Among the 41 participants at 12 weeks after the intervention, only 2 experienced weight gain from baseline, representing 95% of the total. Among the 38 participants at 16 weeks after the intervention, 7 experienced weight gain from baseline, representing 82% of the total.

[0099] The trend of BMI change was consistent with that of body weight (F=30.197, P<0.001) (see Table 3). The fixed-effects model showed that for every unit of time increase, BMI decreased by an average of 0.698 kg / m². 2 (t=-5.49, P<0.001). Compared to baseline, BMI decreased by an average of 1.009 kg / m² 4 weeks after the intervention. 2 (P<0.001), the average weight loss decreased by 2.049 kg / m² 12 weeks after intervention. 2 (P<0.001), 16 weeks after the intervention, BMI remained significantly lower than baseline (mean difference 1.988 kg / m²). 2 (P<0.001) (see) Figure 4 (See upper and middle charts). In terms of time trend, the BMI showed a sustained and significant downward trend in the first 12 weeks after the intervention, with the fastest rate of decline occurring in the first four weeks, averaging a decrease of 0.25 kg / m² per week. 2 During weeks 4-12, the rate of decline slowed, averaging 0.13 kg / m³ per week. 2 There was no statistically significant change in BMI between 12 and 16 weeks after the intervention (mean difference -0.061 kg / m²). 2 The results (t=1.000) indicate that the BMI decrease peaked 12 weeks after the intervention, after which the BMI level tended to stabilize. Gender had a significant effect on BMI (t=-3.505, P<0.001), while age had no significant effect (t=1.309, P=0.197).

[0100] Waist circumference showed an overall decreasing trend during the intervention (F=8.794, P=0.003, see Table 3). However, compared to baseline, the average waist circumference decreased by 2.824 cm at 4 weeks after the intervention (P=0.065), which was not statistically significant. At 12 weeks after the intervention, waist circumference decreased significantly by 5.791 cm from baseline (P<0.001), reaching its peak, after which waist circumference levels tended to stabilize. At 16 weeks, waist circumference was still significantly lower than baseline (mean difference -4.749, P=0.036, see Table 3). Figure 4 (See lower figure). Gender (t=-5.966, P<0.001) and age (t=2.906, P=0.006) both significantly affected waist circumference. The trend of abdominal circumference change was similar to that of waist circumference, with a significant main effect over time (F=13.08, P<0.001, see Table 3). Compared to baseline, abdominal circumference decreased significantly by 6.127 cm at 12 weeks after intervention (P<0.001); it remained significantly decreased at 16 weeks after intervention (mean difference -6.094, P=0.002). Over time, abdominal circumference also decreased from 4 to 12 weeks after intervention, while there was no statistically significant change from 12 to 16 weeks, suggesting that the decrease in abdominal circumference peaked at 12 weeks after intervention, after which it tended to stabilize. After 16 weeks, the abdominal circumference decreased by 6.127 cm from baseline. Sex (t=-3.991, P<0.001) and age (t=2.185, P=0.033) both had a significant effect on waist circumference.

[0101] (4) Changes in lipid metabolism Triglyceride (TG) levels showed a significant decreasing trend during the intervention period (F=4.288, P=0.04, see Table 3). The fixed-effects model showed that TG decreased by an average of 0.146 mmol / L for each additional unit of time (t=-2.071, P=0.040). Compared with baseline, TG decreased by an average of 0.712 mmol / L at 4 weeks post-intervention (P<0.001), and further by 0.670 mmol / L at 12 weeks post-intervention (P=0.003). Although TG levels decreased at 16 weeks post-intervention, this did not reach statistical significance (mean difference 0.375 mmol / L, P=0.418) (see Table 3). Figure 5 (See upper chart). The time trend shows that TG decreased significantly 4 weeks after intervention, with the largest decrease at 12 weeks, and then rebounded after intervention stopped.

[0102] Free fatty acid (FA) levels also showed a significant decreasing trend (F=7.062, P=0.009). A fixed-effects model showed that FA decreased by an average of 0.019 mmol / L for each additional unit of time (t=-2.657, P=0.009). Compared to baseline, FA decreased significantly by 0.036 mmol / L at 4 weeks post-intervention (P=0.036), while changes at 12 and 16 weeks post-intervention were not statistically significant (see [link to relevant data]). Figure 5 (See lower figure). Another free fatty acid indicator, FFA, showed significant changes at some time points. Compared to baseline, FFA increased by an average of 0.137 mmol / L at 4 weeks post-intervention (P < 0.001), while FFA levels at 12 and 16 weeks post-intervention showed no significant difference from baseline (see...). Figure 6 (Top-middle figure). Gender and age had no significant effect on the above lipid metabolism indicators.

[0103] High-density lipoprotein cholesterol (HDL-C) levels fluctuated after the intervention, showing no continuous trend (F=0.316, P=0.575). Intergroup comparisons at time points showed a significant difference only between weeks 12 and 16 after the intervention (mean increase of 0.094 mmol / L, P=0.012), but no significant changes were observed at any time point compared to baseline (see [link to relevant documentation]). Figure 6 (See lower figure). Small, dense low-density lipoprotein cholesterol (sdLDL-C) showed significant differences between some time points. Compared with baseline, sdLDL-C decreased by an average of 6.44 mg / dL at 4 weeks after intervention (P=0.004), 8.16 mg / dL at 12 weeks after intervention (P=0.007), and there was no significant difference at 16 weeks after intervention (mean difference 3.58 mg / dL, P=1.000) (see figure). Figure 7 (Top and middle figures). Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) did not change significantly throughout the intervention (F=0.091, P=0.764 and F=0.035, P=0.851), and there were no statistically significant differences from baseline at any time point.

[0104] (5) Glucose metabolism and insulin sensitivity indicators Insulin levels decreased significantly after the intervention (F=16.492, P<0.001, see Table 3). A fixed-effects model showed that insulin levels decreased by an average of 13.22 μU / mL for each additional unit of time (t=-4.061, P<0.001). Compared to baseline, insulin levels decreased by an average of 37.77 μU / mL at 4 weeks post-intervention (P<0.001), 42.61 μU / mL at 12 weeks post-intervention (P<0.001, 95% CI: -52.01 to -23.53), and remained significantly reduced at 16 weeks post-intervention (mean difference -33.43 μU / mL, P=0.001, 95% CI: -56.87 to -9.98) (see Table 3). Figure 7 (See lower figure). Glycated hemoglobin decreased by only 0.140 units at baseline and week 4 of intervention (P=0.07) (see figure). Figure 8 Blood glucose (GLU) remained stable throughout the intervention, with no significant differences from baseline at any time point.

[0105] (6) Changes in mental symptoms Linear mixed model analysis showed that the total HAMD score decreased over time (F=5.993; P=0.015) (see Table 3). Figure 9 (Top-middle figure). The total HAMA score showed a significant decreasing trend during the intervention period (F=11.388; P=0.001), which was further confirmed by Bonferroni-corrected pairwise comparisons. Compared with baseline, the HAMA scores at weeks 4, 12, and 16 of the intervention were all significantly lower (see [reference]). Figure 9 (See lower figure). The YMRS score (F=1.65, P=0.201), the WHOQOL-BREF quality of life scale (F=1.353, P=0.246), and the Sheehan's Disability Scale (SDS) (F=0.006, P=0.938) remained relatively stable across the four time points, with no significant differences between the time points.

[0106] (7) Changes in cognitive function In the THINC-it cognitive assessment, all four cognitive tasks showed a transient decline at week 4 of the intervention. In the Spotter task, the number of correct answers (P=0.004) and the number of consecutive correct answers decreased from baseline (P=0.018), indicating a decline in attention. In the Symbol Check task, the number of correct answers decreased from baseline (P<0.001), indicating a decline in working memory. In the Codebreaker task, the best reaction time increased from baseline (P=0.025), while the number of correct answers decreased from baseline (P=0.003), indicating a decline in processing speed. In the Trails task, the best reaction time increased from baseline (P<0.001), the number of correct answers significantly increased from baseline (P<0.001), and the number of consecutive correct answers decreased from baseline (P=0.007), indicating a decline in executive function. In the subsequent intervention, cognitive test results at weeks 12 and 16 showed no statistically significant differences compared to baseline, suggesting that the long-term effects of the ketogenic diet on cognitive function are neutral. The fluctuations in cognitive indicators observed at week 4 of the intervention may reflect the adjustment of the balance between neural excitability and inhibition as the brain adapts to the new energy substrate (ketone bodies). With the extension of the intervention period, all cognitive indicators returned to baseline levels at weeks 12 and 16, indicating that the brain had successfully adapted to the new energy metabolism pattern and that cognitive function remained stable.

[0107] This embodiment involved a 12-week ketogenic diet intervention in 53 subjects, and multi-time-point data were analyzed using a linear mixed model. The results showed that the ketogenic diet nutritional composition described in this invention demonstrated multiple benefits in overweight or obese patients with mood disorders, including significant relief of anxiety and improved mood; significant reduction in weight and waist circumference; improvement in metabolic indicators such as blood lipids and insulin; and maintained good overall quality of life. In summary, the results of this embodiment suggest that the ketogenic diet is feasible for patients with mental disorders and may have a positive impact on metabolic health and some mental symptoms.

[0108] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A ketogenic diet nutritional composition, characterized in that, By weight, it includes 60-70 parts of complex fatty acids, 5-10 parts of complex protein peptides, 15-20 parts of dietary fiber, 3 parts of complex vitamins and minerals, and 0-5 parts of carbohydrates.

2. The ketogenic diet nutritional composition according to claim 1, characterized in that, The mass ratio of long-chain fatty acids to medium-chain fatty acids in the complex fatty acids is 1~3:1; the mass ratio of unsaturated fatty acids to saturated fatty acids is 1~3:1; the mass ratio of monounsaturated fatty acids to polyunsaturated fatty acids is 4~8:1; and the mass ratio of Ω-6 polyunsaturated fatty acids to Ω-3 polyunsaturated fatty acids is 0.9~3:

1.

3. The ketogenic diet nutritional composition according to claim 1, characterized in that, The raw materials for preparing the compound fatty acids include at least one of coconut oil, palm oil, flaxseed oil, DHA algal oil, sacha inchi oil, camellia oil, maple seed oil, saxifrage oil, high oleic sunflower seed oil, tomato seed oil, and sea buckthorn seed oil.

4. The ketogenic diet nutritional composition according to claim 1, characterized in that, The complex protein polypeptide includes polypeptide 1, polypeptide 2, polypeptide 3 and polypeptide 4; The amino acid sequences of polypeptides 1 to 4 are shown in SEQ ID NO. 1 to 4.

5. The ketogenic diet nutritional composition according to claim 4, characterized in that, The mass percentage of polypeptides 1 to 4 in the complex protein polypeptide is 0.20% to 1.00%.

6. The ketogenic diet nutritional composition according to claim 1, characterized in that, The raw materials for preparing the complex protein polypeptide include at least one of legumes, grains, dairy products, eggs, nuts, aquatic products, and algae.

7. The ketogenic diet nutritional composition according to claim 1, characterized in that, The total sugar content in the carbohydrates is ≤0.5%.

8. The ketogenic diet nutritional composition according to claim 1, characterized in that, The complex vitamin and mineral formula includes vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B2, vitamin B6, and vitamin B6. 12 Niacin, folic acid, pantothenic acid, calcium, potassium, magnesium, iron, and zinc.

9. The use of the ketogenic diet nutritional composition according to any one of claims 1 to 8 in the preparation of a product, characterized in that, The products include food and / or health products.

10. The use of the ketogenic diet nutritional composition according to any one of claims 1 to 8 in the preparation of a medicament for treating depression and / or anxiety.

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