Carbohydrate-restricted, high-fat diet for improving chronic kidney disease

Abstract

The present invention provides a carbohydrate-restricted high-fat diet for alleviating chronic kidney disease. A fat intake of a 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. A carbohydrate-restricted high-fat diet can increase a glomerular filtration rate in patients with chronic kidney disease and can reduce the blood creatinine level.

Description

[Technical field]

[0001] The present invention relates to a carbohydrate-restricted high-fat diet for improving chronic kidney disease. [Background technology]

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

[0003] Chronic kidney disease (CKD) refers to any kidney disorder that continues for more than three months, and includes all kidney diseases that progress chronically. There are various causes of CKD, but lifestyle-related diseases (diabetes, hypertension, etc.) and chronic nephritis are representative, and it is also closely related to metabolic syndrome. In Japan, it is thought that there are approximately 13.3 million CKD patients (1 in 8 adults over 20 years old), and it is said to be a new national disease. When CKD progresses to renal failure and the kidneys no longer function, dialysis is required to replace them. In Japan, with the aging population and the increase in lifestyle-related diseases, the number of dialysis patients requiring high medical expenses is increasing. However, there is still no effective treatment for CKD, and at present, we have no choice but to rely on conservative treatments such as blood pressure control, blood sugar control, and dietary protein restriction and salt reduction. There is no treatment for CKD that can be expected to have an active renal protective effect. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent No. 5937771 [Patent Document 2] International Publication No. 2017 / 038101 Summary of the Invention [Problem to be solved by the invention]

[0005] An objective of the present invention is to find new target diseases for ketogenic diet (carbohydrate-restricted high-fat diet) therapy. [Means for solving the problem]

[0006] In order to solve the above problems, the present invention includes the following inventions. [1] A low-carbohydrate, high-fat diet for treating chronic kidney disease. [2] The carbohydrate-restricted high-fat diet described in [1] above, wherein the improvement of chronic kidney disease is accompanied by an increase in glomerular filtration rate in patients with chronic kidney disease. [3] A carbohydrate-restricted high-fat diet according to [1] or [2], wherein the improvement of chronic kidney disease is accompanied by a decrease in blood creatinine levels in patients with chronic kidney disease. [4] The carbohydrate-restricted high-fat diet according to any one of [1] to [3], wherein the carbohydrate-restricted high-fat diet limits fat intake to 120 g or more per day based on a real body weight of 50 kg, or limits fat intake to 70% or more of the total daily energy intake. Carbohydrates Limit high-fat diet. [5] The method according to any one of [1] to [4], wherein the fat is a fat containing a medium-chain fatty acid oil. Carbohydrates Limit high-fat diet. [6] The composition according to the above [5], wherein the ratio of medium-chain fatty acid oil in the fat is 30% by mass or more. Carbohydrates Limit high-fat diet. [7] The carbohydrate-restricted high-fat diet according to any one of [1] to [6], wherein the carbohydrate intake is 30 g or less per day based on an actual body weight of 50 kg. Carbohydrates Limit high-fat diet. [8] The method according to any one of [1] to [7], wherein the carbohydrate is a carbohydrate containing lactose. Carbohydrates Limit high-fat diet. [9] The carbohydrate-restricted high-fat diet according to any one of [1] to [8], wherein the carbohydrate-restricted high-fat diet contains 5% by mass to 40% by mass of protein. Carbohydrates Limit high-fat diet.

[10] The carbohydrate-restricted high-fat diet according to any one of [1] to [9], wherein the calorie intake is 1000 kcal or more per day based on an actual body weight of 50 kg. Carbohydrates Limit high-fat diet.

[11] A carbohydrate-restricted high-fat diet contains 25% to 40% by mass of long-chain fatty acid oil and 30% to 50% by mass of medium-chain fatty acid oil. Fat The composition according to any one of the above [1] to

[10] , which contains fatty acid oil, 15% by mass or less of carbohydrate, and 10% by mass to 30% by mass of protein. Carbohydrates Limit high-fat diet. Effect of the Invention

[0007] According to the present invention, a carbohydrate-restricted high-fat diet for improving chronic kidney disease can be provided. A carbohydrate-restricted high-fat diet (ketogenic diet) can increase the glomerular filtration rate and reduce the blood creatinine level in patients with chronic kidney disease. [Brief description of the drawings]

[0008] [Figure 1] This shows the changes in blood acetoacetate levels in 37 subjects analyzed who participated in a clinical study of cancer ketogenic diet therapy. [Diagram 2] This shows the changes in blood β-hydroxybutyrate levels in 37 subjects analyzed who participated in a clinical study of cancer ketogenic diet therapy. [Diagram 3] This is a graph showing the trends in renal function test values ​​for 37 subjects analyzed who participated in a cancer ketogenic diet clinical study; (A) is BUN, (B) is creatinine, (C) is uric acid, and (D) is eGFR. [Figure 4] FIG. 1 shows changes in blood acetoacetate levels in patients who showed a significant improvement in renal function as a result of cancer ketogenic diet therapy. [Diagram 5] FIG. 1 shows changes in blood β-hydroxybutyrate levels in patients who showed a significant improvement in renal function as a result of cancer ketogenic diet therapy. [Figure 6] FIG. 1 shows the time course of creatinine in patients who showed a significant improvement in renal function as a result of cancer ketogenic diet therapy. [Figure 7] FIG. 1 shows the progress of eGFR in patients who showed a significant improvement in renal function as a result of cancer ketogenic diet therapy. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] The present invention provides a carbohydrate-restricted high-fat diet for improving chronic kidney disease. A "carbohydrate-restricted high-fat diet" refers to a diet in which the intake of carbohydrates is lower and the intake of fat is higher than in a normal diet. A "carbohydrate-restricted high-fat diet" is also called a "ketogenic diet." In this specification, "carbohydrate" refers to carbohydrates that are not dietary fiber. In this specification, "carbohydrate" refers to organic compounds whose constituents are monosaccharides. "Carbohydrate" as used in the context of the carbohydrate-restricted high-fat diet of the present invention refers to carbohydrates other than dietary fiber, i.e., "carbohydrates," and "carbohydrate" and "carbohydrate" are used interchangeably.

[0010] In this specification, the term "high-fat diet" refers to a diet in which fat is ingested in an amount equivalent to about 30% or more of the total daily energy intake. The lower limit of the amount of fat ingested by the "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 limit and upper limit values ​​can be combined in any combination. In this specification, the energy ratio is calculated as 9 kcal per 1 g of fat.

[0011] In addition, in this specification, the term "high-fat diet" refers to a diet that requires the intake of about 80 g or more of fat per day, based on an actual body weight of 50 kg. The lower limit of the amount of fat to be ingested by the "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, or about 150 g. The upper limit may be about 180 g, about 170 g, about 160 g, about 150, or about 140 g. These lower and upper limits may be combined in any combination.

[0012] The fats contained in the high-fat diet may be short-chain fatty acid oils, medium-chain fatty acid oils, long-chain fatty acid oils, or any combination thereof. The fats contained in the high-fat diet preferably have a high ratio of medium-chain fatty acid oils. The lower limit of the ratio of medium-chain fatty acid oils to the total fats may be about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, or about 80%. The upper limit may be about 90%, about 80%, about 70%, or about 60%. These lower and upper limits may be combined in any combination.

[0013] Medium chain fatty acid oil refers to oils and fats whose fatty acids have a medium chain length, and is also called MCT (Medium Chain Triglyceride). Representative examples include fatty acids with 6 to 12 carbon atoms, preferably fatty acids with 8 to 12 carbon atoms, fatty acids with 8 to 11 carbon atoms, and fatty acids with 8 to 10 carbon atoms. Medium chain fatty acid oils are more easily digested and absorbed than general oils, and are easily converted into 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).

[0014] Since medium-chain fatty acid oils are present in fats and oils contained in plants such as palm plants, such as coconuts and palm fruits, and dairy products such as milk, medium-chain fatty acid oils extracted (including crude extraction) or refined (including crude refinement) from these fats and oils (preferably vegetable fats and oils such as palm kernel oil) can be used as they are or as raw materials. Alternatively, products produced by chemical synthesis methods or commercially available products may be used as medium-chain fatty acid oils. For example, Nisshin MCT Oil & Powder (manufactured by Nisshin Oillio Co., Ltd.) or extra virgin coconut oil (manufactured by Nisshin Oillio Co., Ltd.) can be used as the medium-chain fatty acid oil.

[0015] In this specification, "carbohydrate restriction" refers to the intake of approximately 100g or less of carbohydrates per day, based on an actual body weight of 50kg. This figure is calculated based on the following statement in the Ministry of Health, Labor and Welfare's "Dietary Reference Intakes for Japanese" (2015 edition) report: "If the basal metabolic rate is assumed to be 1,500kcal / day, the brain's energy consumption is 300kcal / day, which corresponds to 75g of glucose / day. As mentioned above, tissues other than the brain also use glucose as an energy source, so the required amount of glucose is estimated to be at least 100g / day, i.e., the minimum required amount of digestible carbohydrates is estimated to be approximately 100g / day." It is understood that this figure may vary. The upper limit of the amount of carbohydrates ingested per day on a "carbohydrate restricted diet" may be about 90g, about 80g, about 70g, about 60g, about 50g, about 40g, about 35g, about 30g, about 25g, about 20g, about 15g, or about 10g. The lower limit may be about 5g, about 10g, about 15g, about 20g, about 25g, about 30g, or about 60g. These lower and upper limits may be combined in any desired manner.

[0016] In the carbohydrate-restricted high-fat diet of the present invention, the carbohydrate intake during the introduction stage may be set low, for example, limited to about 20 g / day or less, or limited to about 10 g / day or less. By lowering the carbohydrate intake during the introduction stage, it is possible to rapidly induce blood ketone bodies (acetoacetate, β-hydroxybutyrate). However, since the dietary content during the initial stage of introduction is different from conventional eating habits, the carbohydrate-restricted high-fat diet can be continued by gradually reducing the restriction on the carbohydrate intake, and the therapeutic effect can be observed. Therefore, for example, the carbohydrate intake may be started at about 5 to about 15 g / day or thereabout (± about 5 g / day) in the initial stage, maintained at about 15 to about 25 g / day or thereabout (± about 5 g / day) in the second stage, and continued at about 25 to about 35 g / day or thereabout (± about 10 g / day) in the subsequent maintenance stage.

[0017] The carbohydrate-restricted high-fat diet of the present invention may contain monosaccharides such as glucose, 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 carbohydrate restriction range (for example, the above-mentioned daily carbohydrate intake). The carbohydrate-restricted high-fat diet of the present invention may also not contain glucose or polysaccharides having glucose as a basic component. The carbohydrate-restricted high-fat diet of the present invention is preferably one that contains lactose (milk sugar) within the carbohydrate restriction range (for example, the above-mentioned daily carbohydrate intake), more preferably one that contains lactose (milk sugar) without glucose, and particularly preferably one that contains substantially only lactose (milk sugar) as a carbohydrate.

[0018] The carbohydrate-restricted high-fat diet of the present invention may contain protein. The lower limit of the protein content in the carbohydrate-restricted high-fat diet 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 may be combined in any desired manner.

[0019] The carbohydrate-restricted high-fat diet of the present invention is preferably administered 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.

[0020] The carbohydrate-restricted high-fat diet of the present invention preferably has a ketone ratio (lipid / (protein+carbohydrate)) (mass ratio) of about 1 or higher (high in lipids). For example, it may be about 2 or more, or about 2.5 or more. The upper limit of the ketone ratio may be, for example, about 4 or about 3.5. The ketone ratio at the time of introduction is preferably about 2. The total intake of protein and carbohydrate may be any amount as long as the ketone ratio satisfies the above numerical value. It may be about 30 g / day or less, about 20 g / day or less, or about 10 g / day or less. The total intake of protein and carbohydrate may be changed depending on the time. The amount of intake at one time may be any range as long as it is within the range of the daily intake, but is preferably about 10 g or less at one time.

[0021] A preferred embodiment of the carbohydrate-restricted high-fat diet of the present invention includes a carbohydrate-restricted high-fat diet containing about 25% to about 40% by mass of long-chain fatty acid oil, about 30% to about 50% by mass of medium-chain fatty acid oil, about 0% to about 15% by mass of carbohydrate, and about 10% to about 30% by mass of protein.

[0022] The carbohydrate-restricted high-fat diet of the present invention may be an Atkins diet when used for children, or a modified Atkins diet when used for adults. The modified Atkins diet is as follows.

[0023] (1) For the first week, the calorie intake will be approximately 30 kcal / kg body weight based on actual body weight, with no restrictions on fat or protein, and carbohydrates (carbohydrates other than dietary fiber) approximately 10 g or less. Specifically, in the early stages of the program, the actual body weight will be 50 kg, with daily calories of approximately 1500 kcal and a ratio of approximately 140 g fat: approximately 60 g protein: approximately 10 g carbohydrate. The target ketone ratio (fat / (protein + carbohydrates)) is 2. Other nutrients can be consumed without restrictions. Necessary trace elements and vitamins can be taken appropriately through supplements, etc. The period can be extended or shortened as needed, from a few days to a few weeks.

[0024] (2) From the second week to the third month, the amount of carbohydrate and the intake of medium-chain fatty acids using ketone formula and MCT oil are adjusted based on the blood ketone body value. For example, guidance is given to achieve acetoacetate of 500 μmol / L or more and β-hydroxybutyrate of 1000 μmol / L or more, and if possible, the goal is acetoacetate of 1000 μmol / L or more and β-hydroxybutyrate of 2000 μmol / L or more. The daily intake of carbohydrates is about 20g or less, with daily calories of about 1400 to about 1600 kcal, a ratio of about 120 to about 140g of lipids: about 70g of protein: about 20g of carbohydrates, and a ketone ratio of about 1 to about 2. For calorie supplementation, MCT oil and ketone formula can be preferably used. The period can be expanded or contracted as appropriate, and the start may be slightly before or after the second week, and the end may be slightly before or after the third month (a delay of 1, 2 weeks or several weeks is acceptable).

[0025] (3) From the third month onwards, the maximum intake of carbohydrates will be 10 g at one time and approximately 30 g per day, except for the above (2).

[0026] The carbohydrate-restricted high-fat diet of the present invention can be provided in an appropriate combination of 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-delivered meals, home-delivered lunches, frozen lunches, etc. It can also be provided as a carbohydrate-restricted high-fat diet kit including ingredients such as main dishes, side dishes, soups, etc. and cooking recipes. The carbohydrate-restricted high-fat diet of the present invention can also be provided in the form of frozen foods, dairy products, chilled foods, nutritional foods, liquid foods, nursing care foods, beverages, etc.

[0027] The present invention provides a carbohydrate-restricted high-fat composition for improving chronic kidney disease. The carbohydrate-restricted high-fat composition of the present invention can be used to satisfy the intake pattern (fat intake, carbohydrate intake, protein intake, calorie intake, etc.) required for the carbohydrate-restricted high-fat diet of the present invention.

[0028] More preferred embodiments of the carbohydrate-restricted high-fat composition of the present invention include Ketone Formula (817-B; Meiji Co., Ltd.) and compositions having equivalent compositions, as well as modified versions thereof. Modified versions of Ketone Formula include, for example, Ketone Formula (817-B) with further reduced carbohydrates and / or proteins, and Ketone Formula (817-B) with each component independently altered by about ±5%, about ±10%, about ±15%, about ±20%, or about ±25%. The composition of Ketone Formula is shown in Tables 1 and 2.

[0029] [Table 1]

[0030] [Table 2]

[0031] The carbohydrate-restricted high-fat composition of the present invention can be used as the carbohydrate-restricted high-fat diet of the present invention (preferably the modified Atkins diet).

[0032] The carbohydrate-restricted high-fat diet and carbohydrate-restricted high-fat composition of the present invention can be used to improve chronic kidney disease (CKD). Chronic kidney disease refers to a case in which some kind of kidney disorder continues for more than three months. Renal disorder is judged based on pathological diagnosis, image diagnosis, urine test (proteinuria, etc.), blood test (creatinine, BUN, etc.), estimated glomerular filtration rate (eGFR), etc. Chronic kidney disease occurs due to a variety of causes, such as lifestyle-related diseases such as aging, diabetes, hypertension, dyslipidemia, and hyperuricemia; autoimmune diseases such as chronic nephritic syndrome and collagen disease; urological diseases such as urinary tract stones; side effects of drugs (nonsteroidal anti-inflammatory drugs, etc.); and genetics (polycystic kidney disease, etc.).

[0033] As shown in the examples below, the present inventors have confirmed that, when the carbohydrate-restricted high-fat diet of the present invention was applied to a renal cancer patient who had undergone left total nephrectomy and right partial nephrectomy, the creatinine level significantly decreased 3 months after the start of the diet, and the eGFR significantly increased compared to before the start of the diet. Here, at the time of filing the present application, no medicines that increase eGFR have been reported. For example, Perkovic, J. et al. (N Engl J Med 2019; 380:2295-2306) conducted a double-blind randomized study using canagliflozin (an oral SGLT2 inhibitor) in type 2 diabetes patients with kidney disease, and reported that the risk of renal failure and cardiovascular events in patients administered canagliflozin was significantly reduced. However, as shown in Figure 3B of this paper, the eGFR of patients administered canagliflozin was suppressed from decreasing compared to placebo, but the eGFR did not increase. Therefore, the effect of the present invention, which has been demonstrated to significantly increase eGFR, was completely unpredictable to those skilled in the art.

[0034] The present invention also includes the following inventions. A method for improving chronic kidney disease, comprising having a patient with chronic kidney disease ingest a carbohydrate-restricted, high-fat diet. A carbohydrate-restricted, high-fat diet used to improve chronic kidney disease. Use of a carbohydrate-restricted, high-fat diet to improve chronic kidney disease. A carbohydrate-restricted, high-fat diet to increase glomerular filtration rate in patients with chronic kidney disease. A method for increasing glomerular filtration rate in a patient with chronic kidney disease, comprising having the patient consume a carbohydrate-restricted, high-fat diet. A carbohydrate-restricted, high-fat diet used to increase glomerular filtration rate in patients with chronic kidney disease. Use of a carbohydrate-restricted, high-fat diet to increase glomerular filtration rate in patients with chronic kidney disease. EXAMPLES

[0035] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these.

[0036] Example 1: Clinical study of ketogenic diet therapy for cancer 1-1 Test Method (1) Participants The study participants were stage 4 cancer patients with a performance status (PS) of 2 or less who were able to take oral intake. Fifty-five cancer patients (24 men and 31 women) participated. The mean age was 55.8 ± 12.1 years, and 42 patients had received chemotherapy, 32 had surgery, and 17 had received radiation.

[0037] (2) Ketogenic diet From the first week after the first meal, the calorie intake was 30 kcal / kg / day based on actual body weight. There were no restrictions on fat or protein, and the target carbohydrate intake (carbohydrates other than dietary fiber, equivalent to sugar; same below) was 10g or less / day. For example, for an actual body weight of 50kg, the daily calorie intake was 1500 kcal, fat 140g, protein 60g, and carbohydrate 10g. The target ketone ratio [fat (g): (protein (g): carbohydrate (g))] was 2:1. Other nutrients could be consumed without restrictions. Necessary trace elements and vitamins were taken appropriately using supplements, etc. When introducing the ketogenic diet, the subjects consumed meals according to a menu created by a nutritionist.

[0038] From one week to three months later, the dietary content was set based on the blood ketone body measurement. The blood ketone body values ​​were instructed to be 500 μmol / L or more for acetoacetate and 1000 μmol / L or more for beta-hydroxybutyrate, with the goal of 1000 μmol / L or more for acetoacetate and 2000 μmol / L or more for beta-hydroxybutyrate. Carbohydrates were limited to 20g / day or less. For example, for a patient with actual body weight of 50kg, the daily calorie ratio was 1400-1400kcal, lipids 120-140g, protein 70g, and carbohydrates 20g. The ketone ratio [lipid (g): (protein (g): carbohydrates (g)] was targeted to be 2:1-1:1. In addition, "MCT Oil" (manufactured by Nisshin Oillio Group Co., Ltd.) or "Ketone Formula" (manufactured by Meiji Co., Ltd.) was used to supplement calories.

[0039] (3) Blood sampling and biochemical testing Blood samples were collected before the start of the ketogenic diet, and 1 week, 1 month, 2 months, and 3 months after starting the ketogenic diet to measure blood acetoacetate, blood beta-hydroxybutyrate, blood urea nitrogen (BUN), creatinine, and uric acid. Estimated glomerular filtration rate (eGFR) was calculated based on creatinine level, age, and sex.

[0040] Of the 55 participants, 5 did not complete the study, 11 discontinued the study, and 2 were excluded from the analysis, leaving 37 participants (15 men and 22 women) for the final analysis. The mean age at the start of the study for the final analysis participants was 54.8±12.6 years, mean height was 162.5±9.5 cm, mean weight was 55.5±13.2 kg, and BMI was 20.9±3.7. The diseases were lung cancer in 6 cases, colon cancer in 8 cases, breast cancer in 5 cases, ovarian cancer in 1 case, bladder cancer in 1 case, and other cancers in 16 cases. Thirty-two cases had received chemotherapy, 25 cases had surgery, and 13 cases had received radiation.

[0041] 1-2 Results (1) Changes in blood ketone bodies Figure 1 shows the change in blood acetoacetate levels from before the start of the ketogenic diet to three months after the start of the diet in the subjects analyzed. Figure 2 shows the change in blood β-hydroxybutyrate levels from before the start of the ketogenic diet to three months after the start of the diet in the subjects analyzed. The average value of acetoacetate remained above 500 μmol / L during the test period, and the average value of β-hydroxybutyrate remained above 1000 μmol / L during the test period.

[0042] (2) Changes in renal function test values Figure 3 shows the changes in renal function test values ​​from before the start of the ketogenic diet to three months after the start of the diet. (A) shows the results for BUN, (B) for creatinine, (C) for uric acid, and (D) for eGFR. Creatinine after three months was significantly lower than at the start of the diet, and eGFR after three months was significantly higher than at the start of the diet, demonstrating that the ketogenic diet has the effect of improving renal function. Note that the significant increase in uric acid after the start of the ketogenic diet is due to the diet and is unrelated to renal function.

[0043] [Example 2: Remarkably Effective Case] The data for patients who experienced significant improvement in renal function as a result of cancer ketogenic diet therapy are shown below. 2-1 Medical History The patient was a 58-year-old man with renal cancer (weight 64.6 kg, body fat percentage 23.9%). He was diagnosed with renal cancer in May 2011, and underwent left total nephrectomy and right partial nephrectomy on May 12. Right lung metastasis (S10) was found in 2013, and thoracoscopic surgery was performed in November. Metastasis to the 11th thoracic vertebra was found in 2016, and a laminectomy was performed. He started taking Votrient orally in 2017. Nivolumab infusion was administered in 2018. In the same year, metastasis from the 8th thoracic vertebra to the left 7th rib was found, and cryotherapy was started. In 2019, metastasis to the left 5th rib was found, and stereotactic radiation therapy was performed. In the same year, metastasis was found in bilateral hilar lymph nodes, mediastinal lymph nodes, pancreas, and subcutaneous lymph nodes. He then started a ketogenic diet.

[0044] 2-2 Results (1) Changes in blood ketone bodies Figure 4 shows the change in blood acetoacetate from before the start of a ketogenic diet until three months after initiation. Figure 5 shows the change in blood β-hydroxybutyrate from before the start of a ketogenic diet until three months after initiation. Acetoacetate was over 2000 μmol / L after one and two months, and about 1700 μmol / L after three months. β-hydroxybutyrate remained at about 4000 μmol / L from one month to three months after initiation.

[0045] (2) Changes in renal function test values Figure 6 shows the change in creatinine levels from before the start of the ketogenic diet until 3 months later. Figure 7 shows the change in eGFR from before the start of the ketogenic diet until 3 months later. Creatinine levels decreased and eGFR increased after the start of the ketogenic diet, indicating that the ketogenic diet significantly improved renal function in patients who had undergone left total nephrectomy and right partial nephrectomy.

[0046] The present invention is not limited to the above-described embodiments and examples, and various modifications are possible within the scope of 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 for increasing glomerular filtration rate in patients with chronic kidney disease accompanied by a decrease in estimated glomerular filtration rate, comprising: A carbohydrate-restricted high-fat diet in which fat intake is 120 g or more per day based on actual body weight of 50 kg, or 70% or more of the total daily energy intake.

2. The carbohydrate-restricted high-fat diet according to claim 1, which is further used to lower blood creatinine levels in patients with chronic kidney disease.

3. 3. The carbohydrate-restricted high-fat diet according to claim 1 or 2, wherein the fat is a fat containing a medium-chain fatty acid oil.

4. The carbohydrate-restricted high-fat diet according to claim 3, wherein the ratio of medium-chain fatty acid oil in the fat is 30% by mass or more.

5. 5. The carbohydrate-restricted high-fat diet according to any one of claims 1 to 4, wherein the carbohydrate intake is 30 g or less per day based on an actual body weight of 50 kg.

6. 6. The carbohydrate-restricted high-fat diet according to claim 1, wherein the carbohydrate comprises lactose.

7. The carbohydrate-restricted high-fat diet according to any one of claims 1 to 6, wherein the carbohydrate-restricted high-fat diet contains 5% to 40% by mass of protein.

8. 8. The carbohydrate-restricted high-fat diet according to any one of claims 1 to 7, wherein the carbohydrate-restricted high-fat diet has a calorie intake of 1000 kcal or more per day based on a real body weight of 50 kg.

9. The carbohydrate-restricted high-fat diet according to any one of claims 1 to 8, comprising 25% by mass to 40% by mass of long-chain fatty acid oil, 30% by mass to 50% by mass of medium-chain fatty acid oil, 15% by mass or less of carbohydrate, and 10% by mass to 30% by mass of protein.

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