Ketogenic food formulation

Abstract

Ketogenic food formulations comprising fats, fibers, possibly carbohydrates and proteins, wherein the formulations comprise beta-hydroxybutyrate (BHB) di- and poly-esters, and medium chain triglycerides (MCTs) and the formulations for use in a ketogenic diet or for use by individuals affected by particular physiological and / or pathological conditions, on the basis of which particular dietary regimens characterized by a low carbohydrate content may be recommended and beneficial; as well as food products comprising the ketogenic food formulations.

Description

[0001] KETOGENIC FOOD FORMULATION

[0002] FIELD OF THE INVENTION

[0003] The embodiments described here concern ketogenic food formulations and products to be used, by way of a non-limiting example, by individuals affected by particular physiological and / or pathological conditions, on the basis of which particular dietary regimens characterized by a low carbohydrate content may be recommended and beneficial. In particular, the embodiments described here concern a food formulation and a food product which can be obtained using this food formulation for use in a ketogenic diet.

[0004] BACKGROUND OF THE INVENTION

[0005] The ketogenic diet is a nutritional intervention capable of inducing the body to preferentially activate the metabolism of fats, from which ketogenic bodies are synthesized, in particular beta-hydroxybutyrate (BHB), acetoacetate (AcAc) and acetone, which, under certain conditions, are metabolized by the body as an alternative to glucose and used as the main energy source. In order for ketogenic bodies to be produced in high quantities, the intake of carbohydrates, and more specifically sugars, needs to be considerably reduced. This is why the ketogenic diet is characterized by a high fat content, a normal protein intake and a low carbohydrate content, characteristics that are described by the ketogenic ratio, that is, the weight ratio of grams of fat to grams of carbohydrates plus proteins (Wirrell, 2008).

[0006] Food products that meet the ketogenic ratio and can be consumed by individuals following the ketogenic diet are known. A ketogenic diet with a high ketogenic ratio (for example 4: 1) induces on average a higher production of ketogenic bodies and is associated, in the case of drug-resistant epilepsy for example, with a higher anti-epileptic efficacy. Conversely, a diet with a high fat content may not be very palatable, therefore a ketogenic diet with a lower ketogenic ratio (for example 1.5- 3:1) is better tolerated (Hee Seo et al., 2007) and therefore easier to follow. The level of ketosis generally achieved during the ketogenic diet, called nutritional ketosis, ranges from 0.5 mM to 8 mM of blood ketogenic bodies (Saris & Timmers, 2022); the onset and maintenance of nutritional ketosis correlates with the clinical efficacy of the ketogenic diet (Kossoff et al., 2018), which is followed for long periods of time by patients.

[0007] The ketogenic diet was initially used in the treatment of drug-resistant epilepsy, but over the years it has been studied for the treatment of other diseases such as Alzheimer’s, Parkinson’s, type II diabetes, certain types of cancer, obesity (Dowis & Banga, 2021), multiple sclerosis (Storoni & Plant, 2015), migraine (Caminha et al., 2022), rheumatoid arthritis (Ciaffi et al., 2021).

[0008] Ketogenic foods, such as for example those described in International Application WO 2021 / 111483 Al in the name of the Applicant, consist mainly of fats, proteins and fibers, while carbohydrates, a source of sugars, are considerably reduced (< 8%). These characteristics make these foods suitable to be integrated into a ketogenic diet plan.

[0009] In ketogenic foods, the use of non-digestible carbohydrates such as resistant starches, fibers or cellulosic substances is preferred to traditional complex carbohydrates or simple sugars. In particular, fibers do not induce an increase in blood sugars since they are not metabolized by the body, but they pass the gastrointestinal tract and are excreted (non- fermentable fibers) or are used by the intestinal microbiota for the production of short-chain fatty acids (fermentable fibers); this means that the fibers present in ketogenic products do not have an adverse effect on the elevation of ketosis.

[0010] The technological properties of fibers influence the characteristics of the foodstuffs in which they are used. The properties with the greatest technological impact on products include, by way of example, solubility, viscosity, the ability to form gels, the ability to retain water or oil. The presence of specific fibers can therefore have an influence on the texture of the finished product, it can help stabilize a foodstuff, it can help to keep solids suspended in an aqueous product or influence the perception of the taste of a foodstuff (A. L. Nelson, High-fiber ingredients, 2001, Eagan press handbook series, chapters 2 and 5). The technological properties of fibers, combined with the fact that they are not absorbed by the body and do not induce an increase in blood glucose, therefore make them suitable to be used in ketogenic formulations.

[0011] Another ingredient that can be used in ketogenic formulations is erythritol, a polyalcohol with sweetening power that, after being ingested, is excreted in the urine without being metabolized and consequently does not have an impact on ketosis (Hiele et al., 1993) and blood glucose.

[0012] MCT (Medium Chain Triglycerides) fats, medium chain triglycerides with a number of carbon atoms ranging from 6 to 12, are particularly suitable to be used in ketogenic formulations, since they are able to rapidly induce an increase in ketosis. This is related to the fact that MCTs pass directly into the portal vein and reach the liver where, in the absence of glucose and insulin, they can be metabolized to ketogenic bodies. MCTs are therefore able to increase ketosis and reduce the time required to reach it compared to other fats when included in a ketogenic diet regimen (Harvey et al., 2018), but also to induce a state of moderate nutritional ketosis (0.5-1 mmol / L of ketogenic bodies) when used as dietary supplements (about 10-20 g of MCTs, even in the presence of carbohydrates). In the latter case, the duration of MCT-induced ketosis is prolonged by 4-5 hours (Vandenberghe et al., 2020). MCTs are naturally contained in fats of vegetable origin, such as coconut and palm fat for example, or they are contained in synthetic fats, which can be defined as pure MCTs, specifically developed to provide a high content of only these triglycerides. Both of these sources of MCTs can be contained in ketogenic formulations.

[0013] Foodstuffs, including those defined as ketogenic, have a food matrix that can be defined as the set of the interactions between the components of the formulation. These interactions take place at different levels and induce the formation of specific macro- and micro-structures within the foodstuff itself. During digestion, the matrix modulates the effects of the different nutrients, making them more or less available to the body (Capuano & Janssen, 2021), thus acting on the bioaccessibility of the nutrients (fraction released during digestion) and their bioavailability (fraction actually absorbed and available to the body) (Aguilera, 2019). At the technological level, therefore, the ingredients and the matrix of a certain product can be selected and studied so as to optimally and gradually release a nutrient that has, as its ultimate goal, a positive impact on the consumer’s health.

[0014] One way to achieve an increase in ketosis without having to follow the ketogenic diet is represented by the use of exogenous ketogenic bodies, mainly in the form of esters or salts conveyed in formulations to be taken in a diet-free regimen (Stubbs et al., 2017). Several types of exogenous ketogenic bodies have been developed in recent decades: hydroxybutyrate esters (Clarke et al., 2012), hydroxybutyrate salts (Stefan et al., 2020); butanediol esters (Stubbs et al., 2023), tris-hydroxybutyrate glyceryl ester (International Application No. WO 2021 / 070208 Al in the name of the Applicant). Once ingested, the salts of the exogenous ketogenic bodies directly release BHB in an enzyme-independent manner, while the esters of the exogenous ketogenic bodies are hydrolyzed by esterases and carboxylesterases, releasing BHB or BHB precursors (such as butanediol for example) which are assimilated by the body, increasing ketosis in a dose-dependent manner (Clarke et al., 2012). In particular, ketogenic bodies consisting of a glycerol backbone to which between one and three BHB molecules are esterified are processed by endogenous lipases. Most lipases, also known as carboxylesterases, are capable of preferentially or exclusively hydrolyzing the groups present at the outer positions of a triglyceride, that is, those linked to the first and third carbons of the glycerol backbone. Some lipases manage to act on each of the glycerol’s three carbon atoms, thus also leading to the hydrolysis of the group present in the second carbon. Although these lipases lead to a complete hydrolysis of the triglyceride, the reaction kinetics involving positions 1 and 3 are much faster than those involving position 2 (Park & Park, 2022).

[0015] Several experiments have been conducted to measure ketosis kinetics induced by different ketogenic bodies at different concentrations, as reported in Table 1 of fig- 1-

[0016] In general, the trend of ketosis after ingestion of monoesters of the exogenous ketogenic bodies is characterized by an initial peak (within the first 15-120 minutes), followed by a progressive reduction of blood ketogenic bodies. Nutritional ketosis is then maintained at maximum for a few hours (1-6 hours), with a limited window corresponding to ketosis values greater than 2 mM. The salts of the exogenous ketogenic bodies reach a ketosis peak lower than the esters, and the ketosis has an even more limited duration in time (about 2.5 hours). This greatly limits the use of monoesters and salts of the exogenous ketogenic bodies if it is necessary to maintain a sustained and prolonged ketosis over time, for example as a replacement of a ketogenic diet, since products containing these molecules, notoriously not very palatable and very expensive, need to be taken many times during the day or, in the case of salts of the exogenous ketogenic bodies, would result in an overload of cations such as sodium, potassium and magnesium (Daines, 2021). It should be noted that the experiments mentioned in Table 1 of fig. 1 analyze the kinetics of ketosis induced by the ketogenic bodies ingested as such, or at most inserted in very simple formulations. Therefore, the need to prolong the duration of the ketosis over time remains unresolved, which is linked both to the way in which the various exogenous ketogenic bodies are hydrolyzed and metabolized, and also to the formulation in which these molecules are incorporated. Currently, formulations able to guarantee a slow release of ketogenic bodies have not been developed.

[0017] A second negative aspect of formulations with exogenous ketogenic bodies, particularly those containing BHB monoesters, concerns their taste: they are in fact characterized by a bitter taste (Bolyard et al., 2023) that can limit their use, especially if wanting to achieve high doses of ketogenic bodies. In order to overcome the problem of ketogenic bodies’ bitter taste, International Application WO 2011 / 101171 Al mentions the use of flavoring substances, such as licorice, coffee, chocolate, blueberry for example, to be added to the formulation containing exogenous ketogenic bodies so as to make it organoleptically acceptable. The same International Application also mentions other components which are able to improve the sensory perception of the formulation, for example gums, emulsifiers, stabilizers and suchlike, to obtain the desired texture, or an adsorbent material, for example a protein, which is pharmaceutically acceptable and possibly also fulfills a nutritional function; in addition, the possibility of encapsulating the exogenous ketogenic body is mentioned. Another International Application (WO 2020 / 185368 Al) describes a formulation containing exogenous ketogenic bodies which is made palatable, that is, organoleptically acceptable, thanks to the use of propylene glycol, ethanol, water, natural or synthetic flavoring, a high-potency sweetener and a bitter masking agent. Despite the formulation methods able to reduce the perception of bitterness already disclosed in the aforementioned documents, the sensory limit of products containing exogenous ketogenic bodies is still present (Bolyard et al., 2023).

[0018] The main products containing exogenous ketogenic bodies currently on the market are composed of a limited number of ingredients: esters or salts of the ketogenic bodies, in a concentration of approximately 15-20% of the formulation, natural flavors or extracts with flavoring function, natural or artificial sweeteners, polyols and acidifiers, stabilizers, vitamins. These products, developed as ready- to-eat liquids or as powders to be reconstituted with water, are used as supplements with the aim of improving athletic performance in athletes or to improve attention or some cognitive faculties in the general population, mediated by the intake of about 10-20 g of exogenous ketogenic bodies per day.

[0019] Over the years, in parallel with the numerous applications of the ketogenic diet, the potential use of exogenous ketogenic bodies in various pathologies has been studied, such as for example neurodegenerative pathologies (Mild Cognitive Impairment, Alzheimer’s, Parkinson’s, Amyotrophic Lateral Sclerosis - ALS (Poff et al., 2021)), cardiovascular pathologies (Berg-Hansen et al., 2023), diabetes (Falkenhain et al., 2022). However, the products known to date have the disadvantage of not being formulated to maintain a prolonged ketosis over time, since the course of ketosis is exclusively linked to the hydrolysis and metabolism of the monoesters of the exogenous ketogenic bodies and to the dissociation of the salts of the exogenous ketogenic bodies, and in the formulations there are no ingredients that induce a controlled release of the ketogenic body from the food matrix. In addition to this, the dosage indication of the products containing exogenous ketogenic bodies is for one or two servings per day in a normal diet regimen, therefore with a very limited dosage and with no restriction on carbohydrates and sugars, the main ketosis-limiting agents. This does not allow to achieve a sufficient and constant ketosis throughout the entire day, necessary to treat many diseases. Administering a higher number of servings per day would be extremely difficult due to the poor palatability of these products and their high cost.

[0020] Currently, there are no products on the market with exogenous ketogenic bodies also containing macronutrients, fibers and possibly other ingredients, for example MCTs, which are able to guarantee a gradual release of exogenous ketogenic bodies over time and to promote their endogenous production, which can be defined as ketogenic products, which are nutritionally balanced and have good organoleptic properties.

[0021] There is therefore the need to perfect ketogenic food formulations and products which can overcome at least one of the disadvantages of the state of the art.

[0022] The Applicant has devised, tested and embodied the present invention to overcome the shortcomings of the state of the art and to obtain these and other purposes and advantages.

[0023] SUMMARY OF THE INVENTION

[0024] The present invention is set forth and characterized in the independent claims. The dependent claims describe other characteristics of the present invention or variants to the main inventive idea.

[0025] In accordance with the above purposes, the embodiments described here concern ketogenic food formulations and products, that is, suitable for use in a ketogenic diet, which overcome the limits of the state of the art and eliminate the defects present therein.

[0026] In accordance with some embodiments, a ketogenic food formulation comprises fats and fibers, possibly carbohydrates and proteins, wherein the formulation comprises exogenous ketogenic bodies di- and poly-esters, in particular betahydroxybutyrate (BHB) di- and poly-esters, medium chain triglycerides (MCTs) and fibers.

[0027] According to some embodiments, the formulation has a ketogenic ratio, defined as the weight ratio of grams of fat to grams of carbohydrates plus proteins, which promotes the increase in blood ketosis.

[0028] In some embodiments, the formulation or the food product produced therewith can have a ketogenic ratio of at least 1 :1, meaning that the ketogenic ratio can be 1:1 or greater than 1 :1, for example 1.5:1, 2: 1, 2.5: 1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1 or even more, also including other intermediate values between these ratios. For example, the ketogenic ratio can range between 1 :1 and 5:1.

[0029] In some embodiments, the formulation prolongs the release time of BHB from beta-hydroxybutyrate (BHB) di- and poly-esters by endogenous lipases and the production time of endogenous ketogenic bodies from MCTs at the gastric and / or intestinal level, and consequently blood ketosis increases, wherein the release and production of ketogenic bodies are also prolonged by the presence of fibers.

[0030] According to some embodiments, the exogenous ketogenic bodies di- and polyesters comprise, for example, BHB glycerol esters, BHB glycerol ester mixtures, BHB esters and fibers, BHB esters and amino acids, BHB esters and inositol, BHB esters and malic acid, BHB esters and carnitine. A possible example is tris-hydroxybutyrate glyceryl ester (T-BiB). We must clarify that tris- hydroxybutyrate glyceryl ester (T-BiB) is a ketogenic body formed by the esterification of glycerol with three molecules of 3 -hydroxybutyrate. It is therefore a triester in which each hydroxyl group of glycerol is linked to a 3-hydroxybutyric acid, and therefore falls within the definition of polyesters of the ketogenic bodies indicated above.

[0031] According to other embodiments, exogenous ketogenic bodies di- and polyesters comprise, for example, butanediol and BHB esters, butanediol and medium chain fatty acids esters, butanediol glycerol and medium chain fatty acids esters.

[0032] According to some embodiments, the fibers are soluble fibers, insoluble fibers or a combination thereof.

[0033] According to some embodiments, the fibers comprise bamboo fiber and / or psyllium fiber.

[0034] According to some embodiments, bamboo fiber and psyllium fiber are present in the formulation in a reciprocal weight ratio of 0.5:1 to 10:1, for example 3:1, 3.1: 1, 3.2: 1, 3.3:1; 3.4:1, 3.5: 1, 3.6:1, 3.7: 1, 3.8: 1, 3.9:1, 4:1.

[0035] According to some embodiments, the formulation comprises fats containing MCTs as a source of the MCTs, in particular coconut fat and / or palm fat, or pure MCTs.

[0036] According to some embodiments, the formulation comprises pure MCTs or fats containing MCTs between 2% and 35% by weight of the formulation.

[0037] According to some embodiments, the formulation has a weight ratio of BHB di- and poly-esters to MCTs of 0.5:1 to 5:1.

[0038] According to some embodiments, the formulation also comprises one or more ingredients with sensory action.

[0039] According to some embodiments, the formulation described here can include beta-hydroxybutyrate (BHB) di- and poly-esters, for example tris-hydroxy butyrate glyceryl ester (T-BiB), medium chain triglycerides (MCTs), bamboo and psyllium fibers and erythritol.

[0040] According to some embodiments, the ingredients with sensory action comprise one or more of either sweeteners, flavorings, minerals and trace elements, or bitter masking agents. The sweeteners can for example comprise one or more polyols, in particular erythritol.

[0041] According to some embodiments, the formulation comprises beta- hydroxybutyrate (BHB) di- and poly-esters up to 35% by weight of the formulation.

[0042] For example, beta-hydroxybutyrate (BHB) di- and poly-esters from 5% to 25% by weight of the formulation can be provided in the event the formulation is in the form of a gel or cream. In another example, beta-hydroxybutyrate (BHB) di- and poly-esters up to 35% by weight of the formulation can be provided in the event the formulation is in the form of a powder to be reconstituted with water.

[0043] According to some embodiments, the formulation described here is for use in the treatment of one or more of epilepsy, including drug-resistant epilepsy, metabolic diseases (for example GLUT 1), diseases affecting fatty acid oxidation (for example VL-FAOD), mild cognitive impairment (MCI), Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, migraine, type II diabetes, cancer, obesity, rheumatic diseases, for example rheumatoid arthritis, head trauma, refeeding syndrome, autism, metabolic syndrome, chronic obstructive pulmonary disease (COPD), chronic inflammatory bowel diseases (for example Crohn’s disease and ulcerative colitis), age-related macular degeneration (AMD).

[0044] In accordance with some embodiments, a food product comprises, or is obtained from, a formulation according to the present disclosure.

[0045] According to some embodiments, the food product can be in the form of gel, cream or powder to be reconstituted with water, in particular powder containing the di- and poly-esters of the exogenous ketogenic bodies described above, in particular tris-hydroxybutyrate glyceryl ester (T-BiB), encapsulated in order to be reconstituted with water.

[0046] According to some embodiments, the food product can be in the form of a liquid product, capsules, soft capsules, bars, baked goods, ready meals.

[0047] Another aspect described here is a method for producing ketogenic formulations that provides to mix fats, carbohydrates and possibly proteins, and to include in such formulation exogenous ketogenic bodies di- and poly-esters as described here, for example tris-hydroxybutyrate glyceryl ester (T-BiB), medium chain triglycerides (MCTs) and fibers.

[0048] DESCRIPTION OF SOME EMBODIMENTS

[0049] We will now refer in detail to the various embodiments of the invention. Each example is given by way of illustration of the invention and shall not be understood as a limitation thereof. For example, the characteristics shown or described insomuch as they are part of one embodiment can be adopted on, or in association with, other embodiments to produce another embodiment. It is understood that the present invention shall include all such modifications and variants.

[0050] Before describing the embodiments, we must clarify that the present description can provide other embodiments and can be executed in various other ways. We must also clarify that the phraseology and terminology used here is for the purposes of description only, and should not be considered as limitative.

[0051] Unless otherwise defined, all the technical and scientific terms used here and hereafter have the same meaning as commonly understood by a person with ordinary experience in the field of the art to which the present invention belongs.

[0052] Even if methods and materials similar or equivalent to those described here can be used in practice and in the trials of the present invention, the methods and materials are described hereafter as an example.

[0053] In the event of conflict, the present application shall prevail, including its definitions.

[0054] The materials, methods and examples have a purely illustrative purpose and should not be understood restrictively.

[0055] Moreover, all percentages, fractions and ratios between the different components are to be understood as fractions by weight (w / w) with respect to the total weight of the formulation, composition or product, even if not explicitly indicated, unless specified otherwise.

[0056] All the ranges reported here shall be understood to include the extremes, including those that indicate a range “between” two values, unless otherwise indicated.

[0057] The present description also includes the ranges that derive from uniting or overlapping two or more ranges described, unless otherwise indicated.

[0058] The present description also includes the ranges that can derive from the combination of two or more values taken at different points, unless otherwise indicated.

[0059] All percentage ranges reported here are given with the provision that the sum with respect to the overall composition is 100%, unless otherwise indicated. Here and in the remainder of the present description, the term food formulation can be understood to mean, for example, a recipe, assembly, mixture, composition or suchlike, of food ingredients, which can be ready for consumption or can be intended for the production of a food product, for example in the form of a gel, cream or powder, possibly to be reconstituted with water.

[0060] Some embodiments described here concern ketogenic food formulations, that is, food formulations with a ketogenic ratio that promotes ketosis, and therefore for use in the ketogenic diet, comprising:

[0061] - Exogenous ketogenic bodies including, or consisting of, beta-hydroxybutyrate (BHB) di- and poly-esters. The possibility of a combination of the latter is not excluded. One possible example is T-BiB: tris-hydroxybutyrate glyceryl ester, or tris-beta-hydroxybutyrate (T-BiB), which is an exogenous ketogenic body consisting of one glycerol molecule to which three molecules of beta- hydroxybutyrate (triester of glycerol with beta-hydroxybutyrate) are bound by esterification. The molecule contains exclusively R-hydroxybutyrate which, once released from the glycerol molecule by the endogenous lipases present in the digestive tract, enters the bloodstream and induces an increase in ketosis;

[0062] - MCTs: medium chain triglycerides naturally present in vegetable fats (for example coconut fat or palm fat), or contained in fats enriched in this fraction of lipids. MCTs are absorbed at the intestinal level, they enter directly into the liver through the portal vein and can be transformed into ketogenic bodies, thus contributing to blood ketosis. Temporarily, the BHB released by the hydrolysis of the exogenous ketogenic body induces a first increase in ketosis, while the ketogenic bodies produced at the endogenous level by the metabolism of MCTs induce a second increase in ketosis;

[0063] - Fibers: the fibers present in the formulation can be soluble (for example psyllium fiber) or insoluble (for example bamboo fiber), or combinations thereof, and, thanks to their ability to adsorb liquid and / or oily ingredients, are intended to slow down the release of the exogenous ketogenic bodies described above and MCTs from the formulation, thereby prolonging ketosis. In addition, the fibers inserted in the formulation have the ability to influence the texture and sensory characteristics of the formulations.

[0064] The formulations described here are characterized by a ketogenic ratio, defined as the weight ratio of grams of fat to grams of carbohydrates plus proteins. In particular, the food formulations described here contain a high amount of fat, a very low amount of carbohydrates, in particular simple sugars, and possibly proteins in order to recreate a ketogenic ratio that promotes the increase in blood ketosis.

[0065] In some embodiments, the formulation, or the food product made therewith, can have a ketogenic ratio of at least 1 : 1.

[0066] In addition to these macronutrients, one or more ingredients having various functions and which do not inhibit ketosis may be present in the formulations described here, such as, for example, in addition to the aforementioned fibers, ingredients with sensory action.

[0067] The ingredients with sensory action present in the formulations described here can be, for example, sweeteners (artificial sweeteners such as sucralose and advantame, polyols such as erythritol), flavorings (natural, artificial, extracts), minerals and trace elements, bitter masking agents, also referred to hereafter as bitter masking.

[0068] The Applicant has developed different types of food formulations in accordance with the present description: gel, cream, powder containing the above-described exogenous ketogenic bodies, encapsulated to be reconstituted with water. Other embodiments of the formulation can be a liquid product, capsules, soft capsules, bars, baked goods (including for example biscuits, bread, crackers, breadsticks, etc.), ready meals, or a formulation for parenteral nutrition.

[0069] One possible embodiment of the formulation is that of a powder product containing the exogenous ketogenic bodies described above, inserted inside a cap specially designed to be pressed and release the powder into a liquid contained in a bottle or vial under the cap itself, in order to obtain a ready-to-use liquid. The products developed can be foodstuff, foods for special medical purposes, supplements or nutraceutical products.

[0070] In some embodiments of the formulations described here, they can contain the exogenous ketogenic bodies described above between 5% and 25% by weight of the formulation. The percentage of exogenous ketogenic bodies described above contained in powder formulations to be reconstituted with water can instead reach 35%. The formulations described here can contain pure MCTs or MCT-containing fats, such as for example coconut fat, palm fat, palm heart fat, between 2% and 35% by weight of the formulation.

[0071] The formulations described here can have a weight ratio of the above-described exogenous ketogenic bodies to MCTs ranging from 0.5:1 to 5:1.

[0072] The associated use of exogenous ketogenic bodies described above and MCTs or MCT-containing fats allows to have a double source of ketogenic bodies: the first mediated by the metabolism of the exogenous ketogenic body, the second mediated by the metabolism of fats, and in particular of MCTs, which are also transformed into ketogenic bodies.

[0073] The formulations described here have been developed in order to prolong the release time of BHB from the ketogenic bodies described above and the production time of endogenous ketogenic bodies from MCTs at the gastric and / or intestinal level, and consequently the increase in blood ketosis, thanks to the synergistic action of four elements:

[0074] - the release kinetics of BHB from the exogenous ketogenic body molecule by the endogenous lipases;

[0075] - the combination of two sources of ketogenic bodies, namely the exogenous ketogenic body described above and MCT fats;

[0076] - the slow release of the ingredients promoting ketosis by the fibers;

[0077] - the ketogenic ratio, that is, which promotes ketogenesis, of the formulation.

[0078] The release of BHB from the ketogenic body described above by the endogenous lipases provides two steps: initially the ester bonds in position 1 and 3 of the glycerol are hydrolyzed, and then the ester bond in position 2 is hydrolyzed. This leads to a prolongation of the BHB release from the glycerol backbone of the exogenous ketogenic body.

[0079] Alongside this release of BHB, there is the production of endogenous ketogenic bodies induced by the metabolism at the liver level of the MCTs present in the formulation.

[0080] These two phases of release and production of ketogenic bodies are also prolonged by the presence of fibers in the formulations: thanks to their power to adsorb the exogenous ketogenic body and MCTs, the fibers induce a slow release of these ingredients from the formulation at the level of the gastrointestinal tract. This implies that the proportion of exogenous ketogenic body present in the formulation is gradually made available to endogenous lipases and that the absorption and metabolism of MCTs is prolonged over time.

[0081] Finally, the fact that the formulations described here are based on the concept of ketogenic ratio creates the ideal conditions to promote the induction of ketosis. In fact, the formulations described here can be defined as ketogenic products since they contain ingredients that promote ketosis (exogenous ketogenic body, MCTs or MCT-containing fats) and ingredients that prevent the rise of blood sugar and insulin (fibers, possibly polyols, and possibly proteins). These formulations can therefore be integrated into a ketogenic diet or diet-free diet, promoting the consumer’s state of ketosis.

[0082] Depending on whether these foods are used in a normal diet or in a ketogenic diet regimen, and depending on the portions and quantities administered based on the pathology, the formulations and products described here allow to reach a ketosis, from moderate (about 0.5-1 mM) to high, which is constant throughout the 24 hours of a day and which has controlled oscillations.

[0083] The formulations described here contain not only exogenous ketogenic bodies but also macronutrients that give the product a non-secondary caloric intake. The products described here therefore become nutritionally balanced foods that, by covering part of the daily caloric requirement, induce the consumer to reduce the caloric intake deriving from generic foods, which could moderate ketosis.

[0084] A further new nutritional aspect of the formulations described here concerns the use of macronutrients such as MCTs and fibers that could have further positive functions in addition to the direct or indirect elevation of ketosis, such as for example the reduction of inflammatory states or the interaction with the microbiome.

[0085] In the formulations described here, moreover, the perception of the bitter taste of the exogenous ketogenic body can be favorably reduced thanks to the use of a core of ingredients, in particular comprising fibers, for example psyllium and bamboo fibers, possibly combined with ingredients with sensory action, for example erythritol, sweeteners, flavorings, bitter masking agents.

[0086] In addition to a sensory role, the aforementioned core of ingredients also has a technological effect. In fact, it has been designed in such a way that, when used in different quantities in the products developed, it allows to obtain different product textures and forms. The change in texture of the product allows to further mask the perception of the bitter taste of the exogenous ketogenic body in the different products.

[0087] The core of ingredients can for example include bamboo fiber and psyllium fiber, for example in a reciprocal weight ratio of 0.5:1 to 10:1, for example specifically 3: 1.

[0088] The percentage of the total fibers, for example bamboo fiber and psyllium fiber, on the formulation can range from 0.3% to 20% of the formulation, so as to obtain a product with a different consistency: gel-like semi-liquid, a soft yoghurt-like cream, a dense pudding-like cream and others.

[0089] By using a core amount of ingredients as described above of more than 20% of the formulation, possibly added with erythritol, a granulated powder containing exogenous ketogenic body adsorbed to the mixture of dry ingredients can be obtained, which can be coated so as to give an encapsulated powder to be reconstituted with water or used in baked goods or suchlike.

[0090] The use of the formulations thus designed allows to obtain dosages of exogenous ketogenic body corresponding to the use of the product as a supplement (5-15 g of exogenous ketogenic body) and higher dosages, corresponding to a range of 0.5 to 3 g of ketogenic body per kilogram of body weight per day, for use in foods such as for example foods for special medical purposes.

[0091] Another aspect is given by the fact that the fibers, for example the bamboo and psyllium fibers, can be used as structuring agents of different formulations described here, for example keeping the same ratio between the two fibers and varying only their total percentage in the formulation. In addition to this, the fibers, for example the bamboo and psyllium fibers, can be used within ketogenic formulations without inhibiting the increase in ketosis (they are not metabolized and do not induce an increase in glucose or insulin). The presence of the fibers in the different formulations allows to achieve a reduction in the perception of the bitter taste of the exogenous ketogenic body, as demonstrated by the analysis with an electronic tongue and with a panel of trained tasters, as described in detail below.

[0092] As described above, ingredients used to improve the sensory profile of formulations with exogenous ketogenic bodies can also be present within the formulations, such as for example low or high intensity sweeteners, one or more types of flavorings, bitter masking agents, minerals and trace elements and similar ingredients.

[0093] The formulations described here can be used by consumers of different age groups, as well as by consumers with different needs. The products can in fact target the general population or patients suffering from different diseases, such as for example epilepsy, including drug-resistant epilepsy, metabolic diseases, such as for example GLUT 1, fatty acid oxidation disease, for example VL-FAOD, mild cognitive impairment (MCI), Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, migraine, type II diabetes, cancer, obesity, rheumatic diseases, for example rheumatoid arthritis, head trauma, refeeding syndrome, autism, metabolic syndrome, chronic obstructive pulmonary disease (COPD), chronic inflammatory bowel diseases (for example Crohn’s disease and ulcerative colitis), age-related macular degeneration (AMD).

[0094] The Applicant believes that the formulation in accordance with the present disclosure is capable of increasing the level of ketosis over time, and that increased levels of ketosis can activate specific mechanisms of action that can have a benefit in the above mentioned diseases.

[0095] Beta-hydroxybutyrate, the main ketogenic body produced by the metabolism of fatty acids during fasting or following the consumption of foods with a high fat content, is a molecule that has several pleiotropic effects in humans.

[0096] While the role of BHB as an alternative source of energy, particularly for cells of the central nervous system and cardiac cells, is well known, several studies have recently highlighted an important role of BHB in different cellular mechanisms and processes. These include, for example, the modulation of the immune response, the induction of epigenetic modifications that can alter gene expression, the induction of changes in the microbiome, anti-inflammatory action, as well as the reduction in the production of ROS (Reactive Oxygen Species) and of oxidative stress. (Yao et al., 2021).

[0097] It is also known that several neurodegenerative diseases, such as for example Alzheimer’s, Mild Cognitive Impairment (MCI), Parkinson’s, amyotrophic lateral sclerosis (Jensen et al., 2020), as well as diseases affecting the central nervous system, such as for example epilepsy, including drug-resistant epilepsy, (Greene et al., 2003) and diseases that affect the peripheral nervous system, for example age-related macular degeneration (AMD) (Reyes-Reveles et al., 2017), have in common an alteration of the carbohydrate metabolism, which in physiological conditions represents the major source of energy of the central nervous system. This alteration induces an energy crisis that can be bypassed by alternative sources of energy for the central nervous system, such as ketogenic bodies and in particular BHB (Jensen et al., 2020). Similar to these conditions, metabolic diseases such as GLUT-1 or VL-FAOD, characterized by a genetic alteration in transporters or enzymes involved in the metabolism of glucose or long-chain fatty acids, are successfully treated by inducing an increase in ketosis levels and providing the body with an alternative source of energy (Schwantje et al., 2020) (Van Calcar et al., 2020).

[0098] It is also known that during refeeding syndrome there is an exaggerated reaction to the reintroduction of glucose after a prolonged fasting phase, during which a catabolic state is activated, and the body progressively switches from the use of all glucose reserves to ketone metabolism. At the time of the reintroduction of a balanced nutrition containing carbohydrates, glucose again becomes the major energy source; however, this sudden change induces a decompensation of electrolytes at the cellular level that can cause tachycardia, tachypnea and peripheral edema, typical symptoms of this syndrome (Felder et al., 2016). A possible scope of study concerns the maintenance of a high ketosis state during the refeeding phase to allow a more gradual transition from the fasting state to a balanced nutrition.

[0099] Many studies have shown that the synergistic action of BHB as an alternative source of energy and as a molecule capable of activating different effects at the cellular level (neuroprotective and neuromodulatory action, anti-inflammatory action, antioxidant action, vascular action) can be supportive in the treatment of various diseases, such as: i) neurological, for example multiple sclerosis, migraine, brain trauma, autism (Lopez-Ojeda & Hurley, 2023)(Wang et al., 2022) (Li et al., 2021); ii) inflammatory, such as rheumatoid arthritis, chronic obstructive pulmonary disease (COPD); iii) chronic bowel diseases, for example Chron’s disease and ulcerative colitis (Ciaffi et al., 2021) (Kong et al., 2021) (Norwitz et al., 2021); iv) metabolic diseases (type II diabetes, obesity, metabolic syndrome (Dyhka et al., 2023)(Kalayjian & Westman, 2022); vi) some types of cancer (Lopez-Ojeda & Hurley, 2023).

[0100] It is therefore evident that a formulation capable of increasing and maintaining the level of ketosis over time, such as the formulation described here, can have a positive effect in the treatment of diseases such as epilepsy, including drugresistant epilepsy, metabolic diseases, for example GLUT 1, fatty acid oxidation disease, for example VL-FAOD, mild cognitive impairment (MCI), Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, migraine, type II diabetes, cancer, obesity, rheumatic diseases, for example rheumatoid arthritis, head trauma, refeeding syndrome, autism, metabolic syndrome, chronic obstructive pulmonary disease (COPD), chronic inflammatory bowel diseases (for example Crohn’s disease and ulcerative colitis), age-related macular degeneration (AMD).

[0101] EXPERIMENTAL TESTS

[0102] Characterization of the core of ingredients consisting of bamboo and psyllium fibers

[0103] The specific surface area of powders is a very important property in the formulation of a product, since it has different implications: technological (for example regarding the movement of the powders (Bui et al., 2022)) and formulative (for example regarding the dissolution and release of an active ingredient (Bui et al., 2022)), or on the ability of a material to hydrate (WIodarczyk-Stasiak & Jamroz, 2009)). In particular, the specific surface area value can be used to explain the propensity of a material to adsorb a component, for example an active ingredient or a liquid ingredient, and to give a granulate (Sujka & Wiqcek, 2024). The analysis of the specific surface area of a material can be done through the Brunauer, Emmett and Teller (BET) technique, in which nitrogen is used as a test molecule and is placed in contact with the solid to be investigated under precise conditions. Using specific equations, gas adsorption is correlated with the presence and size of pores on the surface of the material itself, which determine its specific surface area (Zielinski, 2013). We analyzed the specific surface area of the bamboo fiber, psyllium fiber, erythritol, and of the mixture of ingredients which comprises bamboo and psyllium fiber in a ratio of 3.9:1 and erythritol, defined in the present disclosure as the core of ingredients. The ingredients were subjected to degassing at 50°C under vacuum overnight, using nitrogen or krypton as adsorbed gas. The specific surface area results expressed in m2 / g are shown in Table 2 below.

[0104] Table 2

[0105] Specific surface area Correlation

[0106] Sample (m2 / g) coefficient R

[0107] 4. Bamboo fiber, psyllium fiber, 0.91 0.9989385 erythritol mix

[0108] The specific surface area of the mixture of the core of ingredients, bamboo and psyllium and erythritol, was in line with the specific surface area values of excipients known to be used in the foodstuff or pharmaceutical sector as porous materials to adsorb liquid ingredients, such as for example starches (native 0.56 m2 / g; modified 1 .66 m2 / g (Sujka & Wiqcek, 2024)) or microcrystalline cellulose (0.78 m2 / g (Hamad et al., 2015)).

[0109] The viscosity of the mixture of the core of ingredients was analyzed with the Brookfield viscometer. The mix of fibers with a 3.9:1 ratio of psyllium to bamboo was analyzed at a concentration in water of 2% following a defined internal procedure for the analysis of the cold viscosity of thickeners which are generally used in food formulations, such as carob seed flour or guar gum for example. The sample was prepared by dissolving the fiber mix in water by mechanical stirring (10 minutes at 1000 rpm with IKA RW 20 stirrer). The viscosity of the sample, analyzed on the Brookfield viscometer at 20 rpm with an RV3 impeller at 30 seconds, was found to be 860 cP, a value very close to that generally obtained during the analysis of guar gum, which is equal to 1000 cP.

[0110] The characterization analyses of the mixture of the core of ingredients reveals the fact that bamboo and psyllium, two fibers known to be used in the food sector, when combined in a 3.9:1 ratio, assume characteristics typical of food and / or pharmaceutical additives typically used to obtain a certain consistency or form of the products, depending on the amount of the mix of fibers present in the formulation. The use of fibers is to be preferred over the use of additives, such as for example modified starches, cellulose, guar gum, since they are not limited from a regulatory point of view and can act as both structuring agents as well as nutrients.

[0111] Organoleptic characterization of the formulations

[0112] Electronic tongue analysis was conducted with Taste-Sensing System SA 402B (Intelligent Sensor Technology Co., Japan). The instrument consists of artificial taste sensors capable of generating electrical impulses of different intensity in response to contact with a given chemical compound (Kobayashi et al., 2010). In the study conducted to analyze the different formulations developed, the BT0 bitterness sensor was used. A calibration line was initially created using concentrations of T-BiB increasing from 0: 10 to 2:10 (used as an example of exogenous ketogenic body according to the present disclosure), dissolved in water. As the concentration of T-BiB increased, the response of the BT0 sensor increased, highlighting a clear dependence between the increase in concentration of the ingredient and the response of the bitterness sensor. Table 3 below shows the formulations containing T-BiB and the core of ingredients as described here, analyzed with the electronic tongue. Formulations similar to those described in the table but without the T-BiB have been used to clear the sensor’s signal of any interferences deriving from ingredients other than the exogenous ketogenic body. All the formulations were diluted in water so as to bring the T-BiB concentration back into the tested range using the calibration line and were analyzed together with the known standard (T-BiB dissolved in water at 0.7:10 concentration) and water (negative control).

[0113] Table 3 _

[0114] Actual

[0115] Core of Dilution of concentration T-BiB % in bamboo and sample for of T-BiB Sample formulation psyllium % in analysis (g: 10 after dilution formulation ml) (g:10 ml) 1. Gel containing T- BiB, core of

[0116] 20.50% 1% 0.7: 10 0.14 bamboo and psyllium and other ingredients

[0117] 2. Cream containing T- BiB, core of

[0118] 17.70% 2% 0.6:10 0.114 bamboo and psyllium and other ingredients 3. Encapsulated powder containing T- BiB, core of 32% 20% 1.4:10 0.45 bamboo and psyllium and other ingredients _

[0119] The background signal of the corresponding formulations without the T-BiB was subtracted from the BTO bitterness sensor signal of each formulation, and the value thus obtained was used to calculate the equivalent in terms of the perceived concentration ofT-BiB using the equation of the calibration line, as shown in Table 4.

[0120] Table 4

[0121] Equivalent in Actual

[0122] BTO

[0123] Standard terms of the concentration sensor

[0124] Sample deviation ingredient’s of T-BiB response (mV) concentration after dilution (mV) (g:10 ml) (g:10 ml)

[0125] 1. Gel containing T- 5.91 0.47 0.12 0.14

[0126] BiB, core of bamboo and psyllium and other ingredients 2. Cream containing T- BiB, core of

[0127] 1.77 0.10 0 0.114 bamboo and psyllium and other ingredients 3. Encapsulated powder containing T- BiB, core of 5.09 0.2 0.09 0.45 bamboo and psyllium and other ingredients

[0128] Reference (T-

[0129] 26.495 1.63 0.75 0.7

[0130] BiB 0,7 g: 10 ml)

[0131] For each formulation, it was possible to compare the actual concentration of T-

[0132] BiB with the equivalent concentration resulting from the bitterness sensor response and thus calculate the percentage reduction in bitterness response. As reported in the graph of fig. 2, the equivalent concentration of T-BiB of the formulations containing the core of ingredients is reduced by 14% for the gel formulation, by 100% for the cream formulation and by 84% for the encapsulated formulation, compared to the actual T-BiB concentration.

[0133] The sensory analysis of the formulations was carried out according to DIN EN ISO 13299 (quantitative sensory analysis). A panel of 8 suitably trained tasters evaluated the bitter taste of the formulations shown in Table 5, comparing it to a known standard consisting of T-BiB dissolved in water, corresponding to a bitterness value of 9, on a scale ranging from 1 (absent, non-perceptible parameter) to 9 (extremely perceptible parameter).

[0134] Table 5

[0135] Sample T-Bib % in formulation

[0136] Reference 1 - solution of T-BiB in water 20%

[0137] 760 - gel containing T-BiB, core of bamboo and

[0138] 20.50% psyllium and other ingredients

[0139] 465 - cream containing T-BiB, core of bamboo and

[0140] 22.4% psyllium and other ingredients

[0141] Reference 2 - solution of T-BiB in water 10%

[0142] 191 - encapsulated powder containing T-BiB, core of 10 1° / * bamboo and psyllium and other ingredients

[0143] Table 5 shows the formulations tested by the sensory panel of trained tasters.

[0144] * concentration of T-BiB after reconstitution of the powder with water.

[0145] Table 6 below shows the mean values of the bitterness values given by the tasters to the formulations, which were found to be 6.9 for the gel formulation, 7.5 for the cream formulation and 7.1 for the encapsulated powder. Applying the ANOVA statistical analysis showed that there is a statistical difference between the reference solutions and the formulations studied.

[0146] Table 6

[0147] 191 Encapsulated

[0148] 760 Gel 465 Cream powder

[0149] Parameter Ref 1 Mean SD Mean SD Ref 2 Mean SD

[0150] Bitter taste 9a6.9b1.1 7.5b0.5 9a7.1b1.6

[0151] The analyses carried out confirm that, in the formulations containing T-BiB and the mixture of the core of ingredients comprising bamboo and psyllium, the bitterness parameter was statistically lower than the reference (pure T-BiB dissolved in water), whether analyzed using electronic tongue analysis or sensory analysis with a panel of trained tasters.

[0152] EXAMPLES

[0153] Example 1 : Gel product

[0154] Portion

[0155] Ketosis-promoting > T-BiB 18 10 ingredients MCTs 15 8.3 Ingredients with multiple Bamboo fiber 0.75 0.4 action Psyllium fiber 0.25 0.1

[0156] Sweeteners 0,3 0.2

[0157] Flavoring 1.5 0.8

[0158] Ingredients with sensory

[0159] Bitter masking 3 1.7 action Additives (for example

[0160] 5 2.8 emulsifiers)

[0161] Portion 55

[0162] Example 2: Cream product

[0163] Portion

[0164] %

[0165] Ketosis-promoting T-BiB 22 10 ingredients Coconut fat 32 14

[0166] Ingredients with multiple Bamboo fiber 1.4 0.6 action Psyllium fiber 0.50 0.2

[0167] Sweeteners 0.6 0.3

[0168] Flavoring 2 0.9

[0169] Ingredients with sensory

[0170] Bitter masking 3 1.4 action

[0171] Additives (for example

[0172] Portion 45

[0173] Example 3 : Powder product to be reconstituted with water

[0174] % (product

[0175] Portion

[0176] % reconstituted with water)

[0177] Ketosis- promoting ingredients

[0178] Ingredients with Bamboo fiber 14 _ 2.7 _ 5.3 multiple action Psyllium fiber 5 1.0 1.9

[0179] Erythritol 12 2.3 4.56

[0180] Sweeteners 0.3 0.06 0.1

[0181] Flavoring 3 0.6 1.1

[0182] Ingredients with

[0183] Bitter masking 0.1 0.02 0.04 sensory action

[0184] Additives (for example 25 4.8 9.5 emulsifiers) water - 80 160

[0185] Portion 100 200

[0186] It is clear that modifications and / or additions of components may be made to the ketogenic food formulations and products as described heretofore, without thereby departing from the field and scope of the present invention, as defined by the claims.

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[0229] Yao, A., Li, Z., Lyu, J., Yu, L., Wei, S„ Xue, L., Wang, H., & Chen, G. Q. (2021). On the nutritional and therapeutic effects of ketone body d-p- hydroxybutyrate. Applied Microbiology and Biotechnology, 105(16-17), 6229- 6243. https: / / doi.org / 10.1007 / s00253-021-11482-w

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Claims

CLAIMS1. Ketogenic food formulation comprising fats and fibers, possibly carbohydrates and proteins, wherein said formulation comprises beta-hydroxybutyrate (BHB) di- and poly-esters, and medium chain triglycerides (MCTs).

2. Formulation as in claim 1, wherein said formulation has a ketogenic ratio, defined as the weight ratio of grams of fat to grams of carbohydrates plus proteins present in said formulation, which promotes the increase in blood ketosis.

3. Ketogenic food formulation as in claim 1 , wherein said ketogenic ratio is at least 1 : 1.

4. Ketogenic food formulation as in claim 1 or 2 or 3, wherein said formulation prolongs the release time of BHB from beta-hydroxybutyrate (BHB) di- and polyesters by endogenous lipases and the production time of endogenous ketogenic bodies from MCTs at the gastric and / or intestinal level, and consequently blood ketosis increases, wherein the release and production of ketogenic bodies are also prolonged by the presence of fibers.

5. Formulation as in any claim from 1 to 4, wherein the fibers are soluble fibers, insoluble fibers or a combination thereof.

6. Formulation as in any claim from 1 to 5, wherein the fibers comprise bamboo fiber and / or psyllium fiber.

7. Formulation as in claim 5, wherein bamboo fiber and psyllium fiber are present in said formulation in a reciprocal weight ratio of 0.5: 1 to 10:1.

8. Formulation as in any claim hereinbefore, comprising fats containing MCTs as a source of said MCTs, in particular coconut fat and / or palm fat and / or pure MCTs.

9. Formulation as in claim 8, wherein said formulation comprises MCTs or fats containing MCTs between 2% and 35% by weight of the formulation.

10. Formulation as in any claim hereinbefore, wherein said formulation has a weight ratio of beta-hydroxybutyrate (BHB) di- and poly-esters to MCTs of 0.5:1 to 5 : 1.

11. Formulation as in any claim hereinbefore, wherein said formulation also comprises one or more ingredients with sensory action, chosen from one or more of either sweeteners, flavorings, minerals and trace elements, bitter masking agents.

12. Formulation as in claim 11, wherein said sweeteners include one or morepolyols, in particular erythritol.

13. Formulation as in claim 12, wherein the formulation comprises betahydroxybutyrate (BHB) di- and poly-esters, medium chain triglycerides (MCTs), bamboo and psyllium fibers and erythritol.

14. Formulation as in any claim hereinbefore, wherein said formulation comprises beta-hydroxybutyrate (BHB) di- and poly-esters up to 35% by weight of the formulation.

15. Formulation as in any claim hereinbefore for use in the treatment of one or more of epilepsy, including drug-resistant epilepsy, metabolic diseases, for example GLUT 1, diseases affecting fatty acid oxidation, for example VL-FAOD, mild cognitive impairment (MCI), Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, migraine, type II diabetes, cancer, obesity, rheumatic diseases, for example rheumatoid arthritis, head trauma, refeeding syndrome, autism, metabolic syndrome, chronic obstructive pulmonary disease (COPD), chronic inflammatory bowel diseases (for example Crohn’s disease and ulcerative colitis), age-related macular degeneration (AMD).

16. Food product comprising, or obtained from, a formulation as in any claim hereinbefore.

17. Food product as in claim 16, in the form of gel, cream or powder to be reconstituted with water, in particular powder containing said beta- hydroxybutyrate (BHB) di- and poly-esters encapsulated in order to be reconstituted with water, or in the form of liquid product, capsules, soft capsules, bars, baked goods, ready meals, or formulation for parenteral nutrition.

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