Nutritional product

Abstract

To provide compositions and methods for use in dietary therapies for treating disorders associated with mitochondrial dysfunction, including epilepsy.SOLUTION: A composition suitable for human consumption comprising decanoic acid and octanoic acid in a ratio of at least 2:1 wt / wt, or substantially free from octanoic acid, and optionally substantially free from any other saturated fatty acid; use of decanoic acid for the preparation of an agent for treating a disease associated with mitochondrial dysfunction; and a method for treating or preventing a disease associated with mitochondrial dysfunction, the method comprising the step of administering to a patient in need of treatment or prevention an effective amount of decanoic acid.SELECTED DRAWING: None

Description

FIELD OF THE INVENTION

[0001] The present invention relates generally to the field of dietary therapy for treating disorders associated with mitochondrial dysfunction, including epilepsy.

[0002] Epilepsy encompasses a wide range of neurological disorders characterized by seizures. Seizures are caused by abnormal neural activity and manifest in a variety of ways, including convulsions and loss of consciousness. In many cases, epilepsy can be managed with anticonvulsant medications. However, for some patients with epilepsy, treatment with conventional medications has minimal effect on seizure activity. While surgery is one option for treating patients with certain types of seizures, many individuals can achieve better management in a more non-invasive manner using a ketogenic diet.

[0003] The ketogenic diet is a high-fat, low-carbohydrate diet that includes sufficient protein for growth and repair. Vitamin and mineral levels are usually insufficient and may need to be provided as dietary supplements. The ketogenic diet works by forcing the body to metabolize fat instead of carbohydrates as its energy source. With low dietary carbohydrates, fat is broken down in the liver into fatty acids and ketone bodies, and these compounds are utilized in further metabolic pathways to generate adenosine triphosphate (ATP) as a chemical energy source.

[0004] Studies have shown clear benefits of the ketogenic diet in treating intractable epilepsy in children and adults. Short-term clinical trials have demonstrated that approximately half of subjects experienced at least a 50% reduction in seizures after six months, and approximately one-third experienced at least a 90% reduction. In some cases, the ketogenic diet is effective enough to allow for reduced levels of prescribed antiepileptic medication, further improving quality of life.

[0005] The ketogenic diet must be strictly controlled to ensure effective seizure prevention while maintaining adequate nutritional value. The diet is developed and optimized on a case-by-case basis under medical supervision, and all foods must be carefully measured and prepared. Deviations from the diet may result in a recurrence of seizures in the patient within a short period of time.

[0006] Although the ketogenic diet is clearly effective, it is difficult to manage in both children and adults. Current approaches to ketogenic diets can be quite restrictive, which can lead to poor compliance, especially in adults. Furthermore, such diets can result in a variety of side effects (including digestive problems, increased serum lipid levels, drowsiness, poor growth, and increased risk of fractures) and are completely unsuitable for some patients. Therefore, identifying the active components of the ketogenic diet responsible for suppressing seizure activity could dramatically simplify treatment and improve the quality of life for a significant number of patients with epilepsy.

[0007] No one knows how the diet works. The body undergoes metabolic changes that affect brain chemistry. One theory attributes the diet's anti-seizure effect to the ketones it produces. Ketones are a product of fat breakdown. The body normally burns glucose for energy. The body can use ketones as an energy source instead of glucose.

[0008] Although the biochemical basis for the effectiveness of the ketogenic diet is unclear, many studies have highlighted its association with altered mitochondrial function and increased mitochondrial biogenesis [Bough, KJ et al., Ann. Neurol. 60, 223-235 (2006)].

[0009] Mitochondria are organelles present in almost all cells in the body. They play a central role in many cellular processes, most notably in energy metabolism. Energy supply is achieved through the integrated function of the electron transport chain (ETC), which receives reducing equivalents from major metabolic pathways (e.g., the tricarboxylic acid (TCA) cycle and fatty acid β-oxidation).

[0010] The weakening of mitochondrial function can occur through congenital or acquired mutations in both nuclear DNA and mitochondrial DNA, or as a result of exposure to environmental factors. Mitochondrial dysfunction is associated with a wide range of clinical conditions and generally affects organs with high energy requirements, such as muscles, liver, kidneys, and the brain. A lack of energy in the form of ATP in the brain leads to neurological dysfunction, which may include seizures. In fact, mitochondrial dysfunction is associated with certain congenital and acquired epilepsy, and is also associated with many other pathologies, including diabetes, dementia (e.g., Alzheimer's disease), and Parkinson's disease.

[0011] Thus, there are multiple direct links between the effects of a ketogenic diet, increased mitochondrial function and biogenesis, and reduced epileptic seizures. Because implementing a ketogenic diet presents various challenges, it is clear that products that target the same biological mechanisms are highly desirable. Summary of the Invention

[0012] The ketogenic diet has several distinct metabolic effects, including increased ketogenesis and elevated plasma levels of medium-chain fatty acids. The correlation between ketone body levels and seizure control is unknown, and relatively little research has been done on the effects of increased fatty acid concentrations.

[0013] The present inventors have determined that decanoic acid, a medium-chain fatty acid whose plasma concentration increases as a result of the ketogenic diet of which MCTs are a part, has a direct effect on mitochondrial function and availability in cells in vitro.

[0014] Thus, decanoic acid may be beneficial in treating epilepsy, particularly in patients currently requiring a ketogenic diet; diseases associated with congenital mitochondrial dysfunction; and patients with acquired mitochondrial disorders, including diabetes, Parkinson's disease, and dementia (e.g., Alzheimer's disease).

[0015] According to a first aspect of the present invention there is provided a composition suitable for human consumption comprising decanoic acid and octanoic acid in a ratio of 2:1 wt / wt, or substantially free of octanoic acid, and optionally substantially free of other saturated fatty acids.

[0016] In other embodiments, the ratio of decanoic acid to octanoic acid is at least 2:1 wt / wt, at least 3:1 wt / wt, at least 4:1 wt / wt, at least 5:1 wt / wt, at least 6:1 wt / wt, at least 9:1 wt / wt, at least 10:1 wt / wt, at least 15:1 wt / wt, at least 20:1 wt / wt, at least 30:1 wt / wt, at least 40:1 wt / wt, at least 50:1 wt / wt, at least 60:1 wt / wt, at least 70:1 wt / wt, at least 80:1 wt / wt, at least 85:1 wt / wt, at least 90:1 wt / wt, at least 95:1 wt / wt, at least 98:1 wt / wt, or at least 99:1 wt / wt. Thus, in one embodiment, the composition is free or substantially free of octanoic acid.

[0017] In one embodiment, decanoic acid is greater than 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, or 59% of the total fatty acid content by weight, at least 60% of the total fatty acid content, at least 65% of the total fatty acid content, at least 70% of the total fatty acid content, at least 80% of the total fatty acid content, at least 90% of the total fatty acid content, or at least 99% or 100% of the fatty acid content by weight. That is, the present invention may use products comprising pure or substantially pure decanoic acid.

[0018] That is, the present invention also encompasses compositions that are free or substantially free of monounsaturated or polyunsaturated fatty acids.

[0019] According to a second aspect of the present invention, there is provided a composition suitable for human consumption having a ketogenic ratio of 0.2 to 0.3:1. Other embodiments include, but are not limited to, ratios of 0.5:1, 1:1 to 5:1, and preferably 4:1 or less, with the majority of the fat being decanoic acid. In one embodiment, the composition has a ketogenic ratio of 2:1 to 4:1. "Ketone ratio" refers to the ratio of the weight of lipid to the combined weight of carbohydrate and protein.

[0020] According to a third aspect of the present invention there is provided a composition suitable for human consumption comprising protein, fat and carbohydrate, providing 2500-3100 kJ per 100 g dry weight, wherein at least 50% of the fat is decanoic acid.

[0021] In one embodiment of the composition of the third aspect of the invention, at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% or 100% of the fat is decanoic acid.

[0022] In one embodiment of the composition of the third aspect of the invention, the composition is free of monounsaturated and / or polyunsaturated fatty acids.

[0023] In one embodiment of the composition of the present invention, the composition provides 2520-3780 kJ / 100 g dry weight. In another embodiment of the composition of the present invention, the composition provides 2520-3180 kJ / 100 g dry weight.

[0024] In one embodiment of the composition of the present invention, the weight ratio of lipid to the total weight of protein and carbohydrate is 1.0 to 1, 2.0 to 1, 5.0 to 1, or, for example, 2.0 to 5.0 to 1, or 2.4 to 4.0 to 1, or 2.6 to 3.8 to 1.

[0025] In one embodiment of the composition of the present invention, the composition is in the form of a human food product.

[0026] In one embodiment of the compositions of the present invention, the composition is formed to deliver a dose of at least about 5 g / L to 150 g / L of decanoic acid per day, hi other embodiments, the dose is about 5 g / L, 10 g / L, 15 g / L, 20 g / L, 30 g / L, 40 g / L, 50 g / L, 60 g / L, 70 g / L, 80 g / L, 90 g / L, 100 g / L, 110 g / L, 120 g / L, 130 g / L, 140 g / L, 150 g / L, 175 g / L, 200 g / L, 225 g / L, 250 g / L, or 500 g / L of decanoic acid per day.

[0027] In one embodiment of the composition of the present invention, the composition is in the form of a complete nutritional product.

[0028] In one embodiment of the composition of the present invention, the composition is in powdered form.

[0029] In one embodiment of the composition of the present invention, the composition is in spray-dried form.

[0030] In one embodiment of the composition of the present invention, the composition is in a form suitable for fortifying food or beverages.

[0031] In one embodiment of the composition of the present invention, the composition is in the form of a food product.

[0032] In one embodiment of the composition of the present invention, the composition is in the form of an oil-in-water emulsion.

[0033] The composition according to the invention may be in the form of oil, mayonnaise, margarine, low fat spread, dairy product (e.g. yogurt), cheese spread, processed cheese, dairy dessert, flavored milk, cream, cultured milk product, cheese, butter, condensed milk product, ice cream mix, soy product, pasteurized liquid egg, bakery product, confectionery product, sweet bar, chocolate bar, high fat bar, liquid emulsion, spray dried powder, freeze dried powder, UHT pudding, pasteurized pudding, gel, jelly, yogurt or a food product with a fat-based or water-containing filling.

[0034] According to a fourth aspect of the present invention, there is provided a use of decanoic acid for preparing a medicament for treating a disease associated with mitochondrial dysfunction. For the avoidance of doubt, "medicament" includes any of the compositions of the present invention, including dietary supplements or complete nutritional products.

[0035] According to a fifth aspect of the present invention, there is provided decanoic acid for treating diseases associated with mitochondrial dysfunction.

[0036] Also provided is the use of decanoic acid according to the invention, wherein the disease is epilepsy, diabetes, Parkinson's disease, dementia (e.g. Alzheimer's disease), or a congenital abnormality of mitochondrial function.

[0037] There is also provided a use of decanoic acid according to the present invention, wherein the treatment of epilepsy includes seizure control.

[0038] According to a sixth aspect of the present invention there is provided a method for the treatment or prevention of a disease associated with mitochondrial dysfunction, the method comprising the step of administering an effective amount of decanoic acid to a patient in need of said treatment or prevention.

[0039] According to a seventh aspect of the present invention there is provided a method of affecting the mitochondrial content of a cell, the method comprising administering decanoic acid to the cell.

[0040] According to an eighth aspect of the present invention there is provided a method of affecting mitochondrial function in a cell, the method comprising administering decanoic acid to the cell.

[0041] According to a ninth aspect of the present invention there is provided a method of affecting mitochondrial availability in a cell, the method comprising administering decanoic acid to the cell.

[0042] According to a tenth aspect of the present invention there is provided a method of regulating the energy supply of a cell, the method comprising the step of administering decanoic acid to a cell.

[0043] The method according to any one of the sixth to tenth aspects of the present invention, wherein the disease is epilepsy, diabetes, Parkinson's disease, dementia (eg Alzheimer's disease), or a congenital abnormality of mitochondrial function.

[0044] In one embodiment, treating epilepsy includes controlling seizures.

[0045] According to an eleventh aspect of the present invention, there is provided decanoic acid, a method or a use according to any one of the fourth to tenth aspects of the present invention, wherein the decanoic acid is administered in the form of a composition according to any one of the first to third aspects of the present invention.

[0046] According to a twelfth aspect of the present invention, there is provided decanoic acid, a method or a use according to any one of the fourth to tenth aspects of the present invention, wherein decanoic acid is administered in a dose of at least about 5 g / l to 250 g / l or at least about 5 g / l to 500 g / l per day.

[0047] Thus, in general terms, the present invention can be summarized as relating to decanoic acid for use in the treatment of diseases associated with mitochondrial dysfunction.

[0048] Decanoic acid, also known as capric acid, is a saturated fatty acid with the formula CH3(CH2)8COOH. Herein, decanoic acid is also referred to as "C10." DETAILED DESCRIPTION

[0049] By elucidating the mechanisms associated with the benefits of the ketogenic diet, the present inventors overcome some of the problems associated with conventional compositions by increasing the palatability of the product and providing a highly effective product that can be formulated to deliver specific levels of C10. Furthermore, the product can treat diseases with the use of C10 that is outside the strict limitations of the classical ketogenic diet.

[0050] Briefly, the classic ketogenic diet uses a ratio to determine and describe fat content. The ketone ratio represents the relationship between grams of fat and total grams of protein and carbohydrates. A 4:1 ratio means that for every gram of total protein and carbohydrates, there are four times as many grams of fat. This ratio was traditionally intended to control the degree of ketosis, and theoretically, increasing the ratio would promote greater ketosis. The MCT ketogenic diet uses the percentage of energy from fat to determine and describe fat content. Two other types of ketogenic diets are the so-called modified Atkins diet and the low-glycemic index (GI) diet, which encourage people to consume more fat. These latter two diets do not officially calculate the percentage or percentage of fat, but typically have a ketone ratio of approximately 1:1. In all four types of ketogenic diets, the percentage of energy from fat ranges from approximately 50 to 92%, but is typically between 70 and 90%. In any case, whatever the form of the meal, a high fat intake is required to be effective, which can have a significant impact on patient compliance. However, according to the teachings of the present invention, it is possible to achieve clinical benefits with a diet outside the traditional ratio ranges described above, as long as the fat contains the appropriate level of decanoic acid according to the present invention.

[0051] If the present invention is delivered as part of a ketogenic diet, the ratio or total fat content can be varied during the course of therapy to achieve nutritional goals and optimize clinical benefit. The ratio can be within the ranges of 1.0:1, 1.5:1, 2.0:1, 2.5:1, 3.0:1, 3.5:1, 4.0:1, 4.5:1, or 5.0:1.

[0052] In one embodiment, the ratio is 2.25:1 to 3.9:1. In another embodiment, the ratio is 2.26 to 3.8:1 or 2.7 to 3.4:1. In further embodiments, the ratio is 3.21:1, 3.23:1, 3.24:1, 3.25:1, 3.26:1, 3.27:1, 3.28:1, or 3.29:1.

[0053] It should be noted that two different individuals of the same age and weight may experience different levels of clinical benefit from the same ratio or amount of fat. Thus, a clinician may need to vary the ratio to achieve optimal clinical benefit. That is, it is within the scope of the present invention to tweak and vary the ratio or total fat content at the beginning or end of a regimen or during a regimen, for example, to increase compliance.

[0054] Decanoic acid is naturally present in, for example, coconut oil and palm kernel oil. It is conceivable that coconut oil and palm kernel oil could form an important basis for the diet. Generally speaking, decanoic acid constitutes approximately 5-8% of the fatty acid composition of coconut oil. That is, food compositions can be envisioned in which the proportion of decanoic acid in the fatty acid composition is approximately 5-8%. On the other hand, octanoic acid constitutes approximately 4.6-10% of the fatty acid composition of coconut oil. Since the present invention has confirmed that C8 is less beneficial than C10, food compositions can be envisioned in which the proportion of octanoic acid in the fatty acid composition is less than 10%, ideally less than 4.6%.

[0055] It will be understood that the lipid fractions useful in the present invention may be in the form of triglycerides, diacylglycerides, monoacylglycerides, phospholipids, lysophospholipids, cholesterol and glycolipids, with triglycerides generally being preferred.

[0056] One can imagine a situation in which C10 is delivered to a patient as a blended product. In this case, it will be understood that, according to the present invention, a relatively high amount of saturated fatty acids is utilized. In particular, the amount of saturated fatty acids is preferably 23-50 g, more preferably 25-45 g, and even more preferably 33-44 g per 100 g of lipid, based on fatty acids. The saturated fatty acids have 8-24 carbon atoms. Preferably, the majority of the saturated fatty acids is decanoic acid (C10:0). That is, for example, 15-50 g, preferably 18-45 g, and more preferably 23-44 g per 100 g of lipid. Particular embodiments include 30-37 g of decanoic acid per 100 g of lipid. Coconut or palm oil is a preferred source for at least 50%, preferably 70-90%, of the lipid fraction. The remainder of the lipid fraction may be selected, for example, from medium-chain triglyceride sources such as fractionated coconut oil, macadamia oil, palm oil or palm kernel oil, or long-chain triglyceride sources such as safflower oil, sesame oil, soybean oil (obtained from soybeans), sunflower oil, high oleic sunflower oil, corn oil, canola oil, walnut oil, evening primrose oil, peanut oil, cottonseed oil, rapeseed oil, olive oil, fish oil, palm olein or algae oil, or mixtures thereof, preferably soybean oil (preferably 2-30), medium-chain triglycerides (having fatty acids with 8-12 carbon atoms; 0-14), marine oil (preferably 0-14 wt%, more preferably 2-12 wt%), and phospholipids, mono- and diglycerides.

[0057] The present invention preferably does not contain monounsaturated and / or polyunsaturated fatty acids. However, if present, the amount of monounsaturated fatty acids is 25 to 48 g, preferably 28 to 43 g, and more preferably 30 to 40 g per 100 g of lipid (based on fatty acids). If present, the amount of polyunsaturated fatty acids (i.e., fatty acids with two or more unsaturated bonds), excluding trans fatty acids, is 16 to 40 g, preferably 20 to 30 g per 100 g of lipid. The lipid fraction preferably also contains ω3 polyunsaturated fatty acids. In particular, polyunsaturated fatty acids constitute more than 0.5 wt%, preferably 1.0 to 10 wt%. The amount of trans fatty acids is less than 20 g, preferably 0 to 10 g, and more preferably 0.2 to 4 g per 100 g of lipid.

[0058] MCT oil is food-grade oil that generally contains more than 90wt% of fatty acid.Traditionally, this fatty acid is composed of saturated fatty acid with 8, 10 or 12 carbon atoms.Although MCT oil can be applied to the present invention, it is preferred to use MCT-based oil in which the majority of saturated fatty acid is decanoic acid.

[0059] Preferably, decanoic acid represents at least 51%, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 wt% of the fatty acid content of the compositions useful in the present invention.

[0060] In one embodiment of the composition useful in the present invention, the ratio of C10 to C8 saturated fatty acids is 60:40, 65:35, 70:30, 75:25, 80:20, 85:15, 90:10, 95:5, or 100:0.

[0061] LCT oil is defined as a food-grade oil containing 15% fatty acids with 20 or more carbon atoms. The present invention may utilize LCT oil, but preferably at levels of 1%, 0.5%, or 0.1% or less per 100g.

[0062] Generally speaking, the administration of the C10 compositions of the present invention can be by oral route or another route into the gastrointestinal tract, or by parenteral route. The form of such administration modes can include conventional forms, such as liquid solutions or suspensions, solid forms suitable for dissolving or suspending in liquid before injection, or emulsions.

[0063] That is, the C10 composition of the present invention can be prepared in a suitable form (which may be a dosage form). While the form is generally suitable for oral administration, the present invention is also applicable to gastric tube feeding. Suitable forms may include tablets, dragees, capsules, gel capsules, powders, granules, solutions, emulsions, suspensions, coated particles, spray-dried particles, and pills containing the C10 composition of the present invention and, optionally, one or more suitable pharmaceutically acceptable carriers. In some embodiments, the C10 composition of the present invention can be inserted into or mixed with food. In some embodiments, the C10 composition of the present invention is in the form of a nutritional product. While nutritional products generally refer to substances intended to supplement the diet, in the present invention, the composition may be in a form intended to be the sole item or food or meal, i.e., a so-called "complete" nutritional product. That is, the present invention can be administered to a subject in the form of a dietary supplement, food, or beverage. A preferred type of food is a medical food, for example, a food in the form of a formulation consumed under medical supervision (such as the ketogenic diet described above) and intended for the specific dietary management of a certain disease or condition.

[0064] As mentioned above, the present invention can be realized in the form of a product suitable for complete human nutrition, or in the form of an oil emulsion, a dietary supplement, or any other suitable product. The product can be suitable for infants, children, and adults. The product comprises a lipid fraction according to the teachings of the present invention, and optionally further comprises a protein fraction, a digestible carbohydrate, a fraction of available and / or unavailable carbohydrates, a nitrogen fraction, and a vitamin fraction, a mineral / trace element fraction, or other components as appropriate to provide a dietary supplement or complete nutritional product.

[0065] Preferably, the protein fraction contains peptides larger than eight amino acids, but this may make the product unsuitable for parenteral administration due to the possibility of allergic reactions. It is preferable to select proteins with strong emulsifying properties, such as certain caseins. However, products available for reconstitution with water or liquid formula should preferably contain lysolecithin, tartrate esters, or a combination thereof as a stabilizing system to obtain a drinkable product.

[0066] The product may preferably be solid or semi-solid, such as a powder, bar, pudding, etc. A semi-solid product is understood to be a product having a solid content of more than 40 g per 100 g of ready-to-use product. More preferably, the semi-solid product is provided as a powder that can be reconstituted with water and used as a single complete meal. The powder may consist of primary particles, agglomerated primary particles, or a mixture of particles of various sizes. Such powders can be produced using methods known in the art, such as spray drying. Spray drying is preferred when adjuvants are used to improve flow properties. The product may also be in the form of an oil that can be used for frying, etc.

[0067] The dry product may be at least partially water soluble, so that liquid foods can be readily prepared as desired: preferably at least 50 wt. % of the dry weight is soluble when dissolved in water at 20°C as 10% (w / v), more preferably at least 75 wt. %.

[0068] The amount of digestible carbohydrates is 0-9 g, preferably 3.2-9 g, more preferably 4-8.6 g, and even more preferably 5-8.2 g per 100 g of dry weight. The amount of protein is 5-20 g, preferably 13-20 g, more preferably 13-18 g, more preferably 13.8-17 g, and even more preferably 14.2-16.2 g per 100 g of dry weight. The amount of lipids is 0 g, 0.1-100 g per 100 g of dry weight, but can be 60-80 g, 63-75 g, or 65-72 g per 100 g of dry weight.

[0069] The inclusion of α-lactalbumin or a high protein content ingredient is particularly suitable. The presence of more than 20 wt% α-lactalbumin in the protein fraction of the product helps to meet the requirements for leucine, lysine, methionine and cysteine, resulting in excellent palatability and digestibility. Preferably, more than 20 wt%, more preferably 40-80 wt%, of the protein fraction consists of α-lactalbumin.

[0070] The digestible carbohydrate fraction can include food-grade ingredients, such as glucose syrup, maltodextrin, lactose, sucrose, galactose, ribose, etc. While some of the other technical features disclosed herein can be applied to obtain a product with superior efficacy, the best results in terms of avoiding side effects and efficacy are obtained if the digestible carbohydrate fraction is in a specific form. It appears beneficial if at least 20%, preferably 30-90%, of the digestible carbohydrate fraction is formed by a source of galactose or ribose. Lactose is considered a suitable ingredient for this purpose. In particular, when such a ketogenic formula containing such digestible non-glucose carbohydrates is consumed, oxidative stress is reduced. Digestibility is determined by applying the Englyst (1999) method.

[0071] Preferably, the protein, lipids, and carbohydrates are derived from at least two different sources, for example, the protein is derived at least in part from an animal, especially a milk source, but optionally also in part from a plant source, the lipids are derived at least in part from a plant source, and the carbohydrates are derived at least in part from a milk source or a combination of milk (lactose) and plants (glucose, maltodextrin, etc.).

[0072] The amounts of minor ingredients are as recommended, but higher than recommended amounts of some specific ingredients may improve efficacy and prevent side effects in pediatric epilepsy.

[0073] To maintain normal growth and development, energy requirements can be calculated according to the individual's energy needs. Useful products for providing to patients, particularly pediatric epilepsy patients, have an energy density of 3.8 to 12.6 kJ / ml, preferably 4.6 to 8.4 kJ / ml, and more preferably 5.0 to 7.2 kJ / ml. For complete nutritional products, an energy density of 5.4 to 6.7 kJ / ml appears to be particularly useful. If the liquid formula has an energy density of 8.4 to 12.6 kJ / ml, the product may also be useful for moderate enrichment of patients.

[0074] The product is usefully relatively energy dense. In some embodiments, the product provides 2520-3780 kJ per 100 grams of dry matter, or for example, 2520-3080 kJ, preferably 2800-3040 kJ per 100 grams of dry matter. The meal may provide 2500-3100 kJ per 100 grams of dry matter, for example, 2505, 2510, 2515, 2520, 2525, 2530, 2535, or 2540-3100, 3095, 3090, 3085, or 3080 kJ per 100 g. In particularly preferred embodiments, the meal includes 2984, 2985, 2986, 2987, 2988, 2989, or 2990 kJ per 100 g.

[0075] The product, suitably after reconstitution into a liquid product, can be administered in amounts of 50-200 g, preferably 75-150 g, per day, calculated on a dry weight basis, for infants under 12 months, in accordance with general energy expenditure recommendations (e.g., those set forth in health authority guidelines). For older children, the preferred daily amount, calculated on a dry weight basis, is 100-360 g, especially 150-300 g. For adults, the preferred daily amount, calculated on a dry weight basis, is 100-500 g, most preferably 150-340 g, because it provides the highest ketogenic potential, sufficient amounts of essential amino acids, carbohydrate backbone, and other nutrients, and is well tolerated and safe.

[0076] Examples of products suitable for use in the present invention are listed below.

[0077] Spray-dried powder formulation: [Table 1]

[0078] Powder formulation: [Table 2]

[0079] Ketogenic diet: [Table 3]

[0080] Emulsions: [Table 4]

[0081] 50% emulsion: [Table 5] [Brief explanation of the drawings]

[0082] [Figure 1] Dose-response curve for C10 over a 6-day incubation period. [Figure 2] Effect of 250 μM C10 for 6 days on complex I activity. [Figure 3] Effect of 250 μM C10 for 6 days on complex I activity. [Figure 4] Electron microscopy. [Figure 5] Electron microscopy data. Experimental example

[0083] Experimental method summary: Mitochondrial enrichment was estimated by assessing the activity of citrate synthase (corrected for total cellular protein content), which is localized to mitochondria and is part of the TCA cycle, and is commonly used as a marker of mitochondrial enrichment.

[0084] To gain a more independent insight into mitochondrial function, the activity of the respiratory chain enzyme, complex I, was also assessed.

[0085] Unless otherwise noted, human neuroblastoma cell line (SH-SY5Y) was utilized throughout this study. Briefly, cells were exposed to a range of concentrations (50–300 μM; dissolved in 0.5% DMSO) of either octanoic or decanoic acid. After 6 days, cells were harvested and citrate synthase activity was determined. Activity was expressed as nmol / min / mg cellular protein.

[0086] In a second experiment, cells were exposed to decanoic acid (250 μM; dissolved in 0.5% DMSO) for 6 days. Cells were then harvested and the activity of complex I was determined. Each experiment was repeated five times, and activity was expressed as nmol / min / mg cellular protein.

[0087] Additionally, SH-SY5Y cells were prepared for electron microscopy (EM) analysis to determine mitochondrial density and morphology after treatment with decanoic acid.

[0088] Finally, the effects of decanoic acid were confirmed in a separate cell line. Primary cultures of human fibroblasts were exposed to 250 μM decanoic acid for 6 days. After incubation, citrate synthase activity was assessed again.

[0089] result: Octanoic acid had no effect on the parameters tested. However, exposure of SH-SY5Y cells to decanoic acid, but not octanoic acid, increased citrate synthase activity compared to control cells (incubated with vehicle alone). This effect was dose-dependent (Figure 1), with a maximum 30% increase (highly significant, p<0.001) occurring at a concentration of 250 μM (expressed as nmol / min / mg cell protein). [Table 6]

[0090] Determination of complex I activity in SH-SY5Y cells after treatment with decanoic acid also showed a significant (p<0.002) increase relative to control experiments (Figure 2). Even when the data were normalized to the activity of citrate synthase, a significant (p<0.05) increase in complex I activity was still evident (Figure 3). The normalization takes into account mitochondrial enrichment after administration of decanoic acid. Therefore, the complex I:citrate synthase activity ratio more accurately demonstrates mitochondrial function, independent of mitochondrial content.

[0091] In all cases, the addition of 0.5% DMSO was shown to have no effect on the parameters tested (compared to untreated cells).

[0092] Electron microscopy studies showed an increase in the number of mitochondria in cells treated with 250 μM decanoic acid (Figure 4). Mitochondria are clearly visible in both images as dense, round, or elongated organelles present in the cytoplasm. Treatment with decanoic acid also altered mitochondrial morphology, appearing more densely stained, likely due to a higher density of cristae within the organelles. These observations are supported by quantitative analysis of the EM data, which showed a significant (p<0.002) increase in the number of mitochondria per cell (Figure 5).

[0093] Finally, the data were confirmed by the observation that primary human fibroblasts exposed to decanoic acid (250 μM) also exhibited a 45% increase in the activity of citrate synthase.

[0094] Conclusion: Exposure to decanoic acid at concentrations comparable to those achieved in plasma by patients on a ketogenic diet significantly increased citrate synthase activity in treated SH-SY5Y neuroblastoma cells. Citrate synthase activity is known to correlate with cellular mitochondrial levels, and thus, these findings raise the possibility that exposure to decanoic acid alters cellular mitochondrial function, possibly by increasing mitochondrial content. This conclusion is further supported by separate data derived from direct observation of cellular mitochondrial content based on electron microscopy. Furthermore, increased complex I activity was observed after administration of decanoic acid. This mitochondrial respiratory enzyme is a direct marker of mitochondrial function, and therefore, these data independently suggest that incubation with decanoic acid increases mitochondrial function. Notably, such findings do not appear to be limited to a single cell type, as a similar increase in citrate synthase activity was evident in primary human fibroblasts exposed to decanoic acid.

[0095] Therefore, such effects of decanoic acid may be therapeutically beneficial for patients with epilepsy who respond to a ketogenic diet. Similarly, decanoic acid may be beneficial for patients with congenital or acquired mitochondrial disorders. Regarding acquired disorders, this may include diabetes, neurodegenerative conditions (e.g., Parkinson's disease), and dementia (e.g., Alzheimer's disease).

[0096] It will be understood that any of the ranges disclosed herein may be used in any combination.

Claims

1. A composition suitable for human consumption comprising decanoic acid and octanoic acid in a ratio of at least 2:1 wt / wt, or substantially free of octanoic acid, and optionally substantially free of other saturated fatty acids.

2. 10. The composition of claim 1, wherein the ratio of decanoic acid to octanoic acid is at least 3:1 wt / wt.

3. 10. The composition of claim 1, wherein the ratio of decanoic acid to octanoic acid is at least 4:1 wt / wt.

4. 10. The composition of claim 1, wherein the ratio of decanoic acid to octanoic acid is at least 5:1 wt / wt.

5. 10. The composition of claim 1, wherein the ratio of decanoic acid to octanoic acid is at least 6:1 wt / wt.

6. 10. The composition of claim 1, wherein the ratio of decanoic acid to octanoic acid is at least 9:1 wt / wt.

7. 10. The composition of claim 1, wherein the ratio of decanoic acid to octanoic acid is at least 10:1 wt / wt.

8. 10. The composition of claim 1, wherein the ratio of decanoic acid to octanoic acid is at least 20:1 wt / wt.

9. The composition of any one of claims 1 to 8, which is substantially free of octanoic acid.

10. The composition of any one of claims 1 to 9, wherein decanoic acid is greater than 50% of the total fatty acid content on a weight basis.

11. The composition of any one of claims 1 to 10, wherein decanoic acid is at least 60% of the total fatty acid content on a weight basis.

12. The composition of any one of claims 1 to 11, wherein decanoic acid is at least 70% of the total fatty acid content on a weight basis.

13. The composition of any one of claims 1 to 12, wherein decanoic acid is at least 80% of the total fatty acid content on a weight basis.

14. The composition of any one of claims 1 to 13, wherein decanoic acid is at least 90% of the total fatty acid content on a weight basis.

15. The composition of any one of claims 1 to 14, wherein decanoic acid is at least 99% of the total fatty acid content on a weight basis.

16. 16. The composition of any one of claims 1 to 15, which is substantially free of monounsaturated or polyunsaturated fatty acids.

17. A composition suitable for human consumption, having a ketone ratio of 0.2:1 to 5:1, with the majority of the fat being decanoic acid.

18. 18. The composition of claim 17 having a ketone ratio of 1:1 to 4:

1.

19. A composition suitable for human consumption, comprising protein, fat and carbohydrates, providing 2500-3100 kJ per 100 g dry weight, wherein at least 50% of said fat is decanoic acid.

20. 19. The composition of claim 17 or 18, wherein at least 60%, 70%, 80%, 90% or 100% of the fat is decanoic acid.

21. The composition according to any one of claims 17 to 20, which is free of monounsaturated and / or polyunsaturated fatty acids.

22. 22. The composition of any one of claims 1 to 21, providing 2520 to 3780 kJ per 100 g dry weight.

23. 23. The composition according to any one of claims 1 to 22, wherein the weight of lipid to the total weight of protein and carbohydrate is 1.5 to 5.0 to 1.

24. 24. The composition according to any one of claims 1 to 23, wherein the weight of lipids to the total weight of protein and carbohydrates is 2.0 to 3.8 to 1.

25. A composition according to any one of claims 1 to 24 in the form of a human food product.

26. 26. The composition of any one of claims 1 to 25, in a form to deliver a dose of at least about 5 g / l to 500 g / l of decanoic acid per day.

27. A composition according to any one of claims 1 to 26 in the form of a complete nutritional product.

28. The composition of any one of claims 1 to 27 in powdered form.

29. The composition of any one of claims 1 to 27 in spray-dried form.

30. A composition according to any one of claims 1 to 29 for fortifying a food or drink.

31. The composition according to any one of claims 1 to 30 in the form of a food product.

32. A composition according to any one of claims 1 to 26 in the form of an oil-in-water emulsion.

33. 33. A composition according to any one of claims 1 to 32 in the form of mayonnaise, margarine, low fat spread, dairy products (e.g. yogurt), cheese spread, processed cheese, dairy desserts, flavoured milk, cream, cultured milk products, cheese, butter, condensed milk products, ice cream mix, soy products, pasteurised liquid eggs, bakery products, confectionery products, sweet bars, chocolate bars, high fat bars, liquid emulsions, spray dried powders, freeze dried powders, UHT puddings, pasteurised puddings, gels, jellies, yogurts or food products with fat-based or water containing fillings.

34. Use of decanoic acid for preparing an agent for treating a disease associated with mitochondrial dysfunction.

35. Decanoic acid for treating diseases associated with mitochondrial dysfunction.

36. 36. Use of decanoic acid according to claim 34 or 35, wherein the disease is epilepsy, diabetes, Parkinson's disease, dementia (e.g. Alzheimer's disease), or a congenital abnormality of mitochondrial function.

37. 37. The use of decanoic acid according to claim 36, wherein the treatment of epilepsy includes seizure control.

38. 1. A method for the treatment or prevention of a disease associated with mitochondrial dysfunction, comprising the step of administering an effective amount of decanoic acid to a patient in need of said treatment or prevention.

39. 1. A method of affecting the mitochondrial content of a cell, the method comprising administering decanoic acid to the cell.

40. 1. A method of affecting mitochondrial function in a cell, the method comprising administering decanoic acid to the cell.

41. 1. A method of affecting mitochondrial availability in a cell, the method comprising administering decanoic acid to the cell.

42. 1. A method for regulating the energy supply of a cell, the method comprising the step of administering decanoic acid to the cell.

43. 43. The method of any one of claims 38 to 42, wherein the disease is epilepsy, diabetes, Parkinson's disease, dementia (e.g. Alzheimer's disease), or a congenital abnormality of mitochondrial function.

44. 44. The method of claim 43, wherein treating epilepsy includes seizure control.

45. 45. The decanoic acid, method or use of any one of claims 34 to 44, wherein the decanoic acid is administered in the form of a composition of any one of claims 1 to 33.

46. 46. ​​The decanoic acid, method or use of any one of claims 34 to 45, wherein the decanoic acid is administered in a dose of at least about 5 g / l to 500 g / l per day.

47. A method for producing a composition according to any one of claims 1 to 33 in the form of a bar, pudding or beverage.

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