High-fat diet with carbohydrate restriction for improving liver diseases

Abstract

The present invention provides a carbohydrate-restricted high-fat diet for alleviating liver disease. The fat intake in the carbohydrate-restricted high-fat diet may be at least 120 g per day on the basis of a real body weight of 50 kg, or at least 70% per day relative to the total daily energy intake. The carbohydrate-restricted high-fat diet can reduce the amount of body fat in a patient with non-alcoholic fatty liver disease, and can also reduce AST, ALT, and γ-GTP.

Description

Technical Field

[0001] The present invention relates to a carbohydrate-restricted high-fat diet for improving liver diseases.

Background Art

[0002] As a type of diet therapy, the "ketogenic diet" is known. The "ketogenic diet" is a carbohydrate-restricted high-fat diet, in which 60 to 90% of the ingested energy is taken from fat. Therefore, the "ketogenic diet" is used as a diet for patients who require a diet with restricted carbohydrates, for example, a diet for treating epilepsy in children (for example, Patent Document 1). In recent years, it has been proposed that diet therapy using this "ketogenic diet" can be a treatment method for cancer patients (for example, Patent Document 2). There are cases that have shown dramatic clinical effects by ketogenic diet therapy.

[0003] In Japan, due to the Westernization of the diet and lack of exercise, the number of obese people is increasing, and non-alcoholic fatty liver disease (NAFLD), which is a phenotypic manifestation of metabolic syndrome in the liver, is increasing. Fatty liver refers to a state in which neutral fat accumulates in the liver, and fatty liver that occurs in people who hardly drink alcohol is called NAFLD. NAFLD includes simple fatty liver that does not progress and follows a benign course, and non-alcoholic steatohepatitis (NASH) that may progress to liver cirrhosis or liver cancer. Causes of NAFLD include obesity (visceral fat accumulation), diabetes, dyslipidemia, hypertension, rapid weight loss or acute starvation, drugs (such as tamoxifen, steroids, amiodarone), and total parenteral nutrition.

[0004] In the epidemiological survey in Japan, out of a group of 11,714 people (5,811 men and 5,903 women) who underwent mass screening, approximately 32% of the men and approximately 9% of the women were diagnosed with NAFLD. Among them, approximately 85% of the men and approximately 87% of the women met the criteria for metabolic syndrome. Among NAFLD patients, the proportion of NASH is 20 - 30%, and it is estimated that there are approximately 2 million NASH patients in the country.

[0005] Now that viral liver diseases are controllable, it is undeniable that NAFLD will become the most important causative disease of liver cirrhosis and liver cancer in the near future. The only treatment for progressive liver cirrhosis accompanied by liver failure is liver transplantation, and currently, there is no established treatment method for NAFLD and NASH based on sufficient evidence.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0007] An object of the present invention is to find a new target disease for ketogenic diet (low - carbohydrate high - fat diet) therapy.

Means for Solving the Problems

[0008] In order to solve the above problems, the present invention includes the following inventions. [1] A low - carbohydrate high - fat diet for improving liver diseases. [2] The low - carbohydrate high - fat diet according to [1] above, wherein the liver disease is non - alcoholic fatty liver disease or non - alcoholic steatohepatitis. [3] The low - carbohydrate high - fat diet according to [1] or [2] above, wherein the improvement of the liver disease is accompanied by a decrease in at least one selected from AST, ALT, and γ - GTP. [4] The carbohydrate-restricted high-fat diet according to any one of [1] to [3] above, wherein improvement of liver disease is accompanied by a decrease in body fat mass. [5] The carbohydrate-restricted high-fat diet according to any one of [1] to [4] above, wherein the fat intake is 120 g or more per day based on a substantial body weight of 50 kg, or 70% or more of the total daily energy intake. [6] The carbohydrate-restricted high-fat diet according to any one of [1] to [5] above, wherein the fat is a fat containing medium-chain fatty acid oil. [7] The carbohydrate-restricted high-fat diet according to [6] above, wherein the ratio of medium-chain fatty acid oil in the fat is 30% by mass or more. [8] The carbohydrate-restricted high-fat diet according to any one of [1] to [7] above, wherein the carbohydrate intake is 30 g or less per day based on a substantial body weight of 50 kg. [9] The carbohydrate-restricted high-fat diet according to any one of [1] to [8] above, wherein the carbohydrate is a carbohydrate containing lactose.

[10] The carbohydrate-restricted high-fat diet according to any one of [1] to [9] above, wherein the carbohydrate-restricted high-fat diet contains 5% to 40% by mass of protein.

[11] The carbohydrate-restricted high-fat diet according to any one of [1] to

[10] above, wherein the calorie intake is 1000 kcal or more per day based on a substantial body weight of 50 kg.

[12] The carbohydrate-restricted high-fat diet according to any one of [1] to

[11] above, which contains 25% to 40% by mass of long-chain fatty acid oil, 30% to 50% by mass of medium-chain fatty acid oil, 15% by mass or less of carbohydrate, and 10% to 30% by mass of protein. [Advantages of the Invention]

[0009] According to the present invention, a carbohydrate-restricted high-fat diet for improving liver disease can be provided. The carbohydrate-restricted high-fat diet (ketogenic diet) can reduce AST, ALT, γ-GTP, and body fat mass in patients with NAFLD. [Brief Description of the Drawings]

[0010]

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Mode for Carrying Out the Invention

[0011] The present invention provides a carbohydrate-restricted high-fat diet for improving liver diseases. The "carbohydrate-restricted high-fat diet" means a diet with less carbohydrate intake and more fat intake than a normal diet. The "carbohydrate-restricted high-fat diet" is also referred to as the "ketogenic diet". In the present specification, "carbohydrate" refers to carbohydrates other than dietary fiber. In the present specification, "carbohydrate" refers to an organic compound having a monosaccharide as a constituent component. In the context of the carbohydrate-restricted high-fat diet of the present invention, "carbohydrate" refers to carbohydrates other than dietary fiber, that is, "carbohydrates", and "carbohydrates" and "carbohydrates" are used interchangeably.

[0012] As used herein, a "high-fat diet" refers to a diet that causes the intake of fat corresponding to about 30% or more of the total daily energy intake. The lower limit of the amount of fat ingested by a "high-fat diet" can be about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90% of the total daily energy intake. The upper limit can be about 95%, about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50% of the total daily energy intake. These lower and upper limits can be arbitrarily combined with each other. In this specification, the energy ratio is calculated at 9 kcal per 1 g of fat.

[0013] In addition, as used herein, a "high-fat diet" refers to a diet that causes the intake of about 80 g or more of fat per day when based on a body weight of 50 kg. The lower limit of the amount of fat ingested by a "high-fat diet" may be about 90 g, about 100 g, about 110 g, about 115 g, about 120 g, about 125 g, about 130 g, about 135 g, about 140 g, about 145 g, about 150 g. The upper limit may be about 180 g, about 170 g, about 160 g, about 150, about 140 g. These lower and upper limits can be arbitrarily combined with each other.

[0014] The fat contained in a high-fat diet may be low-chain fatty acid oil, medium-chain fatty acid oil, long-chain fatty acid oil, or any combination thereof. It is preferable that the high-fat diet contains a high proportion of medium-chain fatty acid oil. The lower limit of the ratio of medium-chain fatty acid oil to the total fat can be about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%. The upper limit may be about 90%, about 80%, about 70%, about 60%. These lower and upper limits can be arbitrarily combined with each other.

[0015] Medium-chain fatty acid oil refers to oils composed of fatty acids with medium-chain lengths in the fatty acids that make up fats and oils, and is also referred to as MCT (Medium Chain Triglyceride). Typically, it refers to those composed of fatty acids with 6 to 12 carbon atoms, preferably those composed of fatty acids with 8 to 12 carbon atoms, those composed of fatty acids with 8 to 11 carbon atoms, and those composed of fatty acids with 8 to 10 carbon atoms. Medium-chain fatty acid oil is more easily digested and absorbed than general oils and is more likely to become energy. Examples of medium-chain fatty acids include hexanoic acid (caproic acid; C6), octanoic acid (caprylic acid; C8), nonanoic acid (pelargonic acid; C9), decanoic acid (capric acid; C10), and dodecanoic acid (lauric acid; C12).

[0016] Since medium-chain fatty acid oil is present in the fats and oils contained in plants such as coconut and palm fruit of the palm family, and dairy products such as milk, the medium-chain fatty acid oil extracted (including crude extraction) or purified (including crude purification) from these fats and oils (preferably vegetable oils such as palm kernel oil) can be used as it is or as a raw material. Alternatively, products or commercial products obtained by chemical synthesis methods may be used as medium-chain fatty acid oil. For medium-chain fatty acid oil, for example, Nisshin MCT Oil & Powder (manufactured by Nisshin Oillio Group) and Extra Virgin Coconut Oil (manufactured by Nisshin Oillio Group) can be utilized.

[0017] In this specification, "carbohydrate restriction" means allowing the intake of approximately 100 g or less of carbohydrates per day based on a substantial body weight of 50 kg. This value is calculated based on the description in the "Dietary Reference Intakes for Japanese" (2015 edition) report of the Ministry of Health, Labour and Welfare, which states that "assuming a basal metabolic rate of 1,500 kcal / day, the energy consumption of the brain is 300 kcal / day, which corresponds to 75 g of glucose per day. Since tissues other than the brain also utilize glucose as an energy source as described above, the required amount of glucose is estimated to be at least 100 g / day, that is, the minimum required amount of digestible carbohydrates is estimated to be approximately 100 g / day." It is understood that this value can vary. The upper limit of the amount of carbohydrates ingested per day by the "carbohydrate-restricted high-fat diet" may be approximately 90 g, approximately 80 g, approximately 70 g, approximately 60 g, approximately 50 g, approximately 40 g, approximately 35 g, approximately 30 g, approximately 25 g, approximately 20 g, approximately 15 g, or approximately 10 g. The lower limit may be approximately 5 g, approximately 10 g, approximately 15 g, approximately 20 g, approximately 25 g, approximately 30 g, or approximately 60 g. These lower and upper limits can be arbitrarily combined with each other.

[0018] The carbohydrate-restricted high-fat diet of the present invention may have a low carbohydrate intake set during the induction period. For example, it may be restricted to approximately 20 g / day or less, or may be restricted to approximately 10 g / day or less. By reducing the carbohydrate intake during the induction period, it becomes possible to rapidly induce blood ketone bodies (acetoacetic acid, β-hydroxybutyric acid). However, since the diet content at the initial stage of induction is different from conventional eating habits, gradually reducing the restriction on the amount of carbohydrate intake enables the continuation of the carbohydrate-restricted high-fat diet and a recognized therapeutic effect. Therefore, for example, initially, the carbohydrate intake may be started at approximately 5 to approximately 15 g / day or around that amount (± approximately 5 g / day), maintained at approximately 15 to approximately 25 g / day or around that amount (± approximately 5 g / day) in the second stage, and continued at approximately 25 to approximately 35 g / day or around that amount (± approximately 10 g / day) in the subsequent maintenance stage.

[0019] The high-fat diet with carbohydrate restriction of the present invention may contain monosaccharides such as glucose (dextrose), fructose, and galactose, disaccharides such as maltose, sucrose, and lactose, or polysaccharides such as starch (amylose, amylopectin), glycogen, and dextrin, or any combination thereof, within the range of carbohydrate restriction (for example, the above-mentioned daily carbohydrate intake). The high-fat diet with carbohydrate restriction of the present invention may also be one that does not contain glucose or polysaccharides having glucose as a basic component. The high-fat diet with carbohydrate restriction of the present invention preferably contains lactose within the range of carbohydrate restriction (for example, the above-mentioned daily carbohydrate intake), more preferably contains lactose but does not contain glucose, and particularly preferably contains substantially only lactose as the carbohydrate.

[0020] The high-fat diet with carbohydrate restriction of the present invention may contain protein. The lower limit of the protein content ratio in the high-fat diet with carbohydrate restriction of the present invention may be about 5% by mass or about 10% by mass. The upper limit may be about 40% by mass, about 30% by mass, or about 20% by mass. These lower and upper limits can be arbitrarily combined with each other.

[0021] The high-fat diet with carbohydrate restriction of the present invention is preferably ingested so that the daily calorie intake is about 20 kcal / kg or more (about 1000 kcal or more for a standard body weight of 50 kg), but is not limited thereto. For example, it may be about 14 kcal / kg / day or more, about 16 kcal / kg / day or more, or about 18 kcal / kg / day or more. Preferably, it is about 22 kcal / kg / day or more, about 24 kcal / kg / day or more, about 26 kcal / kg / day or more, about 28 kcal / kg / day or more, or about 30 kcal / kg / day or more.

[0022] The high-fat diet with carbohydrate restriction of the present invention preferably has a ketone ratio (lipid / (protein + carbohydrate)) (mass ratio) of about 1 or higher (more lipid). For example, it may be about 2 or higher, about 2.5 or higher. The upper limit of the ketone ratio can be, for example, about 4, about 3.5. The ketone ratio at the time of introduction is preferably about 2. The total intake of protein and carbohydrate can be any amount as long as the ketone ratio satisfies the above numerical values. It may be about 30 g / day or less, about 20 g / day or less, about 10 g / day or less. The total intake of protein and carbohydrate may be varied depending on the time. The intake amount at one time may be in any range as long as it is within the range of the daily intake amount, but preferably about 10 g or less at one time.

[0023] As a preferred embodiment of the high-fat diet with carbohydrate restriction of the present invention, there is provided a high-fat diet with carbohydrate restriction containing about 25% by mass to about 40% by mass of long-chain fatty acid oil, about 30% by mass to about 50% by mass of medium-chain fatty acid oil, about 0% by mass to about 15% by mass of carbohydrate, and about 10% by mass to about 30% by mass of protein.

[0024] When the high-fat diet with carbohydrate restriction of the present invention is used for children, the Atkins diet may be used, and when it is used for adults, the modified Atkins diet may be used. The modified Atkins diet is as follows.

[0025] (1) In the first week, the calories are set to about 30 kcal / kg body weight based on the actual body weight, without lipid restriction, without protein restriction, and the target is about 10 g or less of carbohydrate (carbohydrates other than dietary fiber). Specifically, at the initial stage of introduction, assuming the actual body weight is 50 kg, the ratio of about 1500 kcal of calories per day, about 140 g of lipid: about 60 g of protein: about 10 g of carbohydrate is used. The ketone ratio (lipid / (protein + carbohydrate)) is targeted at 2. Other nutrients can be ingested without restriction. Necessary trace elements and vitamins are appropriately ingested with supplements, etc. The period can be appropriately extended or shortened and can be several days to several weeks.

[0026] (2) From the second week to the third month, adjust the carbohydrate intake, ketone formula, and the intake of medium-chain fatty acids with MCT oil based on the value of blood ketone bodies. For example, guide to achieve acetoacetic acid of 500 μmol / L or more and β-hydroxybutyric acid of 1000 μmol / L or more. If possible, aim for acetoacetic acid of 1000 μmol / L or more and β-hydroxybutyric acid of 2000 μmol / L or more. The daily carbohydrate intake should be about 20 g or less, with a ratio of about 1400 - about 1600 kcal of calories per day, about 120 - about 140 g of lipids, about 70 g of protein, and about 20 g of carbohydrates, and target a ketone ratio of about 1 - about 2. When replenishing calories, preferably, MCT oil and the ketone formula can be used. The period can be appropriately extended or shortened. The start can be a little before or after the second week, and the end can be a little before or after the third month (a deviation of 1 or 2 weeks or a few weeks is acceptable).

[0027] (3) After the third month, the single intake of carbohydrates is set at 10 g, and the daily intake is about 30 g or less, and the others are in accordance with the above (2).

[0028] The carbohydrate-restricted high-fat diet of the present invention can be provided by appropriately combining main dishes, side dishes, soups, etc. Therefore, the carbohydrate-restricted high-fat diet of the present invention can be provided in the form of home delivery meals, home delivery bento, frozen bento, etc. Also, it can be provided as a carbohydrate-restricted high-fat diet kit including ingredients and cooking recipes for main dishes, side dishes, soups, etc. Further, the carbohydrate-restricted high-fat diet of the present invention can be provided in the form of frozen foods, dairy products, chilled foods, nutritional foods, liquid foods, nursing foods, beverages, etc.

[0029] The present invention provides a carbohydrate-restricted high-fat composition for improving liver diseases. The carbohydrate-restricted high-fat composition of the present invention can be used to satisfy the intake forms (fat intake, carbohydrate intake, protein intake, calorie intake, etc.) required by the carbohydrate-restricted high-fat diet of the present invention.

[0030] As a more preferred embodiment of the carbohydrate-restricted high-fat composition of the present invention, there are mentioned a ketone formula (817-B; Meiji Co., Ltd.), a composition having the same composition as this and its modifications. Examples of the modified product of the ketone formula include those in which the carbohydrate and / or protein are further reduced in the ketone formula (817-B), and those in which each component of the ketone formula (817-B) is independently changed by ± about 5%, ± about 10%, ± about 15%, ± about 20%, ± about 25%. The compositions of the ketone formula are shown in Table 1 and Table 2.

[0031] [Table 1]

[0032] [Table 2]

[0033] The carbohydrate-restricted high-fat composition of the present invention can be used as the carbohydrate-restricted high-fat diet (preferably the modified Atkins diet) of the present invention.

[0034] The carbohydrate-restricted high-fat diet and the carbohydrate-restricted high-fat composition of the present invention can be used for the purpose of improving liver diseases. Examples of liver diseases include acute viral hepatitis, drug-induced liver injury (antibiotics, antipyretic analgesics, psychotropic drugs, anticancer drugs, Kampo medicines, etc.), chronic hepatitis B, chronic hepatitis C, liver cirrhosis, liver cancer, alcoholic liver injury, primary biliary cirrhosis, autoimmune hepatitis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and the like. As shown in the examples in the latter part, the present inventors have confirmed that, as a result of applying the carbohydrate-restricted high-fat diet of the present invention to lung cancer patients diagnosed with NAFLD, the body fat significantly decreased, and the AST value, ALT value, γ-GTP value, and FIB4-Index decreased below the reference values.

[0035] The present invention also includes the following inventions. A method for improving liver diseases, which comprises allowing a patient with liver diseases to ingest a carbohydrate-restricted high-fat diet. A carbohydrate-restricted high-fat diet used for improving liver diseases. Use of a carbohydrate-restricted high-fat diet for improving liver diseases. A method for reducing at least one selected from AST, ALT, and γ-GTP in a liver disease patient, comprising allowing the liver disease patient to ingest a carbohydrate-restricted high-fat diet. A carbohydrate-restricted high-fat diet used for reducing at least one selected from AST, ALT, and γ-GTP in a liver disease patient. Use of a carbohydrate-restricted high-fat diet for reducing at least one selected from AST, ALT, and γ-GTP in a liver disease patient.

Example

[0036] Hereinafter, the present invention will be described in detail by way of examples, but the present invention is not limited thereto.

[0037] 〔Example 1: Clinical study of the cancer ketogenic diet〕 1-1 Test method (1) Participants Cancer patients in stage 4 with a performance status (PS) of 2 or less and who were able to take orally were targeted. 55 cancer patients (24 males and 31 females) participated. The average age was 55.8 ± 12.1 years, and the treatment history included 42 cases of chemotherapy, 32 cases of surgery, and 17 cases of radiation.

[0038] (2) Ketogenic diet From the first time to one week later, the calorie was set to 30 kcal / kg / day based on the actual body weight. There was no restriction on lipids, no restriction on protein, and the target for carbohydrates (carbohydrates other than dietary fiber, equivalent to sugars hereinafter) was 10 g or less per day. For example, in the case of an actual body weight of 50 kg, the ratio was 1500 kcal of calories per day, 140 g of lipids, 60 g of protein, and 10 g of carbohydrates. The ketone ratio [lipids (g): (protein (g): carbohydrates (g))] was targeted at 2:1. Other nutrients could be ingested without restriction. Necessary trace elements and vitamins were appropriately ingested using supplements, etc. When introducing the ketogenic diet, the patients were made to ingest a diet according to the menu prepared by a dietitian.

[0039] From 1 week to 3 months later, the diet content was set with reference to the measured values of blood ketone bodies. Regarding the values of blood ketone bodies, it was guided so that acetoacetic acid would be 500 μmol / L or more and β-hydroxybutyric acid would be 1000 μmol / L or more, aiming for acetoacetic acid to be 1000 μmol / L or more and β-hydroxybutyric acid to be 2000 μmol / L or more. Carbohydrates were set to 20 g / day or less. For example, in the case of a substantial body weight of 50 kg, the ratio was 1400 - 1600 kcal of calories per day, 120 - 140 g of lipids, 70 g of protein, and 20 g of carbohydrates. The ketone ratio [lipids (g) : (protein (g) : carbohydrates (g))] was targeted at 2:1 - 1:1. Also, for calorie supplementation, "MCT oil" (manufactured by Nisshin Oillio Group, Ltd.) or "Ketone Formula" (manufactured by Meiji Co., Ltd.) was used.

[0040] (3) Blood sampling and biochemical tests Blood sampling was performed before the start of the ketogenic diet, 1 week, 1 month, 2 months, and 3 months after the start of the ketogenic diet, and blood acetoacetic acid, blood β-hydroxybutyric acid, AST, ALT, γ-GTP, and ALP were measured. Also, at the same time, various body composition values were measured using a body composition analyzer (In Body 720).

[0041] Among the 55 participants, there were 5 who did not undergo the test, 11 who discontinued the test, and 2 who were excluded from the analysis. The final analysis subjects were 37 cases (15 males and 22 females). The average age at the start of the test for the final analysis subjects was 54.8 ± 12.6 years old, the average height was 162.5 ± 9.5 cm, the average weight was 55.5 ± 13.2 kg, and the BMI was 20.9 ± 3.7. The diseases were 6 cases of lung cancer, 8 cases of colorectal cancer, 5 cases of breast cancer, 1 case of ovarian cancer, 1 case of bladder cancer, and 16 cases of other cancers. The treatment histories were 32 cases of chemotherapy, 25 cases of surgery, and 13 cases of radiation.

[0042] 1 - 2 Results (1) Changes in blood ketone bodies Figure 1 shows the changes in blood acetoacetic acid from before the start of the ketogenic diet to 3 months after the start in the subjects. Figure 2 shows the changes in blood β-hydroxybutyric acid from before the start of the ketogenic diet to 3 months after the start in the subjects. The average value of acetoacetic acid was maintained at 500 μmol / L or more during the test period, and the average value of β-hydroxybutyric acid was maintained at 1000 μmol / L or more during the test period.

[0043] (2) Changes in liver function test values Figure 3 shows the changes in liver function test values from before the start of the ketogenic diet to 3 months after the start in the subjects. (A) shows the results of AST, (B) shows the results of ALT, (C) shows the results of γ-GTP, and (D) shows the results of ALP. ALT was significantly decreased 2 months and 3 months after the start of the ketogenic diet compared with the start. Also, γ-GTP was significantly decreased at any time point from 1 week after the start of the ketogenic diet to 3 months after the start compared with the start. From this result, it became clear that the ketogenic diet has an effect of improving liver function.

[0044] (2) Changes in body composition values Table 3 shows the body weight, BMI (Body Mass Index), limb muscle mass, SMI (Skeletal Muscle Index), body fat mass, body fat percentage, and ECW / TBW (extracellular fluid volume / total body water volume) before the start of the ketogenic diet and 3 months after the start in the subjects. At the time point 3 months after the start of the ketogenic diet, the body weight, BMI, body fat mass, and body fat percentage were significantly decreased. On the other hand, the limb muscle mass, SMI, and ECW / TBW did not change. From this result, it became clear that the ketogenic diet decreases the body weight and BMI by decreasing the body fat mass.

[0045]

Table 3

[0046] 〔Example 2: Remarkable efficacy example〕 Data of patients who showed a remarkable liver function improvement effect by the cancer ketogenic diet therapy are shown below. 2-1 Medical history The patient is a 55-year-old male with lung cancer. In November 2017, left pleural effusion was detected, and he visited a major hospital. As a result of performing PET-CT, tissue biopsy, etc., he was diagnosed with lung cancer and started taking crizotinib (Xalkori (registered trademark)) (1 tablet of 250 mg / capsule, twice a day). The ketogenic diet was started in January 2018. At the start of the ketogenic diet, height: 184 cm, weight: 85.1 kg, BMI: 25.1 kg / cm 2 , body fat mass: 23.3 kg, SMI: 7.9 kg / cm 2 , AST: 112 U / L, ALT: 165 U / L, γ-GTP: 117 U / L, FIB4-Index (an index of liver fibrosis, (age × AST) / (platelet count × ALT 1 / 2 ), with a possibility of liver fibrosis if 1.30 or more): 1.74. From the medical history, this patient was not found to have autoimmune liver disease or viral liver disease, and from the drinking history and the above test values, it was recognized that he had NAFLD.

[0047] 2-2 Results (1) Changes in blood ketone bodies Figure 4 shows the changes in blood acetoacetic acid from before the start of the ketogenic diet to 4 months after the start. Figure 5 shows the changes in blood β-hydroxybutyric acid from before the start of the ketogenic diet to 4 months after the start. Acetoacetic acid increased to about 1800 μmol / L 1 month after the start of the ketogenic diet and then decreased, but was maintained at about 700 μmol / L after 3 months. β-Hydroxybutyric acid increased to about 3600 μmol / L 1 month after the start of the ketogenic diet and then gradually decreased, and the value 4 months later was about 1700 μmol / L.

[0048] (2) Changes in liver function test values Figure 6 shows the changes in liver function test values from before the start of the ketogenic diet to 4 months after the start. (A) shows AST, (B) shows ALT, (C) shows γ-GPT, and (D) shows the change in FIB4-Index. For this patient, the AST before the start of the ketogenic diet was approximately 110 U / L, the ALT was approximately 165 U / L, the γ-GPT was approximately 120 U / L, and the FIB4-Index was 1.74, all of which were abnormally high. However, the AST dropped below the upper limit of the reference value 1 week after the start of the ketogenic diet and maintained values within the reference range thereafter. The ALT and γ-GPT dropped below the upper limit of the reference value 1 month after the start of the ketogenic diet and maintained values within the reference range thereafter. The FIB4-Index decreased to 0.88 1 week after the start of the ketogenic diet (a value of 1.30 or less indicates a low likelihood of liver fibrosis) and maintained this value thereafter. This result indicates that the ketogenic diet therapy significantly improved the liver function of the lung cancer patient diagnosed with NAFLD.

[0049] (3) Changes in body composition values Figure 7 shows the changes in body composition values from before the start of the ketogenic diet to 3 months after the start. (A) shows body weight, (B) shows BMI, (C) shows body fat mass, and (D) shows the change in SMI. The body weight decreased from 85.1 kg before the start of the ketogenic diet to 76.2 kg 3 months after the start (the standard weight for a height of 184 cm is 74.5 kg), and the BMI decreased from 25.1 (obesity level 1) to 22.5, indicating normal weight. The body fat mass decreased from 23.3 kg to 17.0 kg, but the SMI, which reflects muscle mass usage, was 7.9 before the start and 7.7 after 3 months, indicating little change. This result shows that the ketogenic diet therapy reduced the patient's body fat, and it is considered that the patient's liver function improved and NAFLD improved due to the reduction of body fat by the ketogenic diet therapy.

[0050] Note that the present invention is not limited to the above-described embodiments and examples, and various changes are possible within the scope shown in the claims. Embodiments obtained by appropriately combining the technical means disclosed in different embodiments are also included in the technical scope of the present invention.

Claims

1. A carbohydrate-restricted high-fat diet containing medium-chain fatty acid oil for reducing AST, ALT, and FIB4-Index in patients with non-alcoholic fatty liver disease or non-alcoholic steatohepatitis.

2. The carbohydrate-restricted high-fat diet according to claim 1, which is further for reducing γ-GTP.

3. The carbohydrate-restricted high-fat diet according to claim 1 or 2, which is further for reducing body fat mass.

4. The carbohydrate-restricted high-fat diet according to any one of claims 1 to 3, wherein the fat intake is 120 g or more per day based on a substantial body weight of 50 kg, or 70% or more of the total daily energy intake.

5. The carbohydrate-restricted high-fat diet according to any one of claims 1 to 4, wherein the ratio of medium-chain fatty acid oil in the fat is 30% by mass or more.

6. The carbohydrate-restricted high-fat diet according to any one of claims 1 to 5, wherein the carbohydrate intake is 30 g or less per day based on a substantial body weight of 50 kg.

7. The carbohydrate-restricted high-fat diet according to any one of claims 1 to 6, wherein the carbohydrate is a carbohydrate containing lactose.

8. The carbohydrate-restricted high-fat diet according to any one of claims 1 to 7, which contains 5% to 40% by mass of protein.

9. The carbohydrate-restricted high-fat diet according to any one of claims 1 to 8, wherein the calorie intake is 1000 kcal or more per day based on a substantial body weight of 50 kg.

10. The carbohydrate-restricted high-fat diet according to any one of claims 1 to 9, which contains 25% to 40% by mass of long-chain fatty acid oil, 30% to 50% by mass of medium-chain fatty acid oil, 15% by mass or less of carbohydrates, and 10% to 30% by mass of protein.

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