EP4676451A1

EP4676451A1 - Composition comprising medium-chain triglycerides, omega-3 and choline for use in a method of treatment of cognitive decline and dementia

Info

Publication number: EP4676451A1
Application number: EP24717279.4A
Authority: EP
Inventors: Giulio TORELLO; Roberto PISATI
Original assignee: Global Pharmacies Partner In Forma Abbreviata GPP Srl Srl
Current assignee: Global Pharmacies Partner In Forma Abbreviata GPP Srl Srl
Priority date: 2023-03-09
Filing date: 2024-03-11
Publication date: 2026-01-14
Also published as: IT202300004461A1; WO2024184869A1

Abstract

The present invention relates to a mixture, and a composition comprising said mixture, comprising medium-chain triglycerides MCT, omega-3 and choline. In particular, the present invention relates to a mixture, and a composition comprising said mixture, comprising medium-chain triglycerides MCT, omega-3 and choline for use in a method of treatment, preferably a preventive method of treatment, of a subjective memory disorder, a mild cognitive decline (MCI), a dementia or an Alzheimer's disease.

Description

COMPOSITION COMPRISING MEDIUM-CHAIN TRIGLYCERIDES, OMEGA-3 AND CHOLINE FOR USE IN A METHOD OF TREATMENT OF COGNITIVE DECLINE AND DEMENTIA

The present invention relates to a mixture, and a composition comprising said mixture, comprising or, alternatively, consisting of: medium-chain triglycerides MCT, omega-3 and choline. In particular, the present invention relates to a mixture, and a composition comprising said mixture, comprising or, alternatively, consisting of: medium-chain triglycerides MCT, omega-3 and choline for use in a method of treatment, preferably in a preventive method of treatment, of a subjective memory disorder, a mild cognitive decline (MCI), a dementia or an Alzheimer's disease.

It is known that as a good proportion of people become aware of a progressive decline in their cognitive functions as they age; both memory and mental abilities may decline.

A first disorder is a subjective memory disorder that results in a deterioration of one's cognitive abilities, in the absence of neuropsychological deficits. The most common symptom is a decline in thinking and/or memory to a level that creates a discomfort and relative distress.

A second disorder is Mild Cognitive Impairment (MCI), which results in a clinical condition characterized by worsening cognitive function, memory, and thinking. This deficit, however, does not interfere with functional abilities, allowing for autonomous and independent living. It is possible that from a condition of MCI one may, in some cases, see a slow progression of this condition to dementia or Alzheimer's disease.

Finally, a third disorder is Alzheimer's disease, which is the most common form of dementia characterized by the presence of amyloid plaques in brain tissue and a subsequent loss of cognitive function. The symptoms of Alzheimer's disease depend on the degree of cognitive decline. However, initially the patient presents with short-term memory loss with long-term memory episodes.

Among the preventive factors of cognitive disorders, a key role is certainly played by the diet and the health of our gut ecosystem. A number of studies and meta-analyses confirm the preventive role of a Mediterranean diet in neurodegeneration and in promoting synaptic function. It is important, for example, to optimize the ratio between animal and vegetable proteins, introducing greater amounts of the latter and preferring among the former those derived from fish and eggs, and to adopt a varied diet rich in antioxidant and anti-inflammatory foods.

And when diet cannot ensure adequate micro- and macronutrient intake, or when lifestyle makes it necessary, it is useful to take individualized action with specific nutraceuticals and supplements.

Neurons are known to communicate with each other through synapses (knob-like bulges known as buttons). Synaptic release of neurotransmitters requires a lot of energy. The brain is a high-energy-demand organ. It requires a constant supply of energy to perform its many functions, such as information processing, critical thinking, and problem solving. Mitochondria generate this energy by converting nutrients into a form of energy called ATP. Without sufficient ATP production, our brains would not be able to function optimally. Mitochondria are crucial for memory preservation. Maintaining healthy mitochondria also protects against Alzheimer's disease. They are the cell organelles, equipped with their own DNA, that produce the energy needed by cells for all vital functions. The way to maintain healthy mitochondria is also the one that prevents cancer and heart disease or a number of other age-related diseases: exercise and a diet rich in antioxidants. Memory consolidation is modulated by endogenous adenosine triphosphate (ATP) acting on purinergic receptors in the hippocampus. During synaptic transmission, neurons and astrocytes release ATP, which acts on purinergic P2 receptors. There are some studies on the role of purines in enhancing mammalian hippocampal activity (LTP) in learning and memory processes.

Therefore, it is important to be able to study and examine the role of ATP in the hippocampus in learning and memory formation and to determine whether ATP is involved in memory to determine the effect of hippocampal P2Y receptor inhibition. It is, in addition, desirable to have a formulation containing specific and selected nutrients so that the mitochondria can provide energy, in the form of ATP, necessary for proper brain function.

From the above, it is clear that there remains a high interest and need, among operators in the field at all levels, for new formulations, based on specific ingredients, that have been studied and fine-tuned, both qualitatively and quantitatively, to be able to provide and guarantee a proper contribution of micro- and macronutrients, as well as substances with antioxidant and/or anti-inflammatory activity. In addition, there is a felt need and necessity to be able to have new nutraceutical formulations or food supplements that are effective and well assimilated and capable of presenting acceptable compliance, especially in the case of elderly subjects to be treated, both from the point of view of organoleptic and digestibility and form of administration.

The Applicant, after extensive and intensive research and development activity, has finalized a formulation that can adequately address the above needs.

Specifically, the Applicant has finalized a formulation that can provide an appropriate amount of nutrients by providing, for example, an adequate amount of omega-3 DHA/EPA in the presence, preferably, of mediumchain triglycerides, in order to provide an adequate amount of energy, in the form of ATP, to maintain and/or improve memory and cognitive status, and prevent cognitive decline in elderly subjects or patients suffering from Alzheimer's or senile dementia.

It is an object of the present invention, a mixture and a composition, comprising said mixture, for use in a method of treatment of 1) subjective memory disorder, 2) mild cognitive decline (MCI), 3) dementia, or 4) Alzheimer's disease, having the characteristics as set forth in the united claims.

Preferred embodiments of the present invention are given below, in the detailed description that follows, as examples only and, therefore, not limiting the scope of the present invention.

In the context of the present invention, the terms "composition" and "formulation" may be used as terms having the same meaning, and the phrase "composition/formulation of the present invention" also includes foods for special medical purposes (FSMPs) according to Regulation (EU) 609/2013 and regulated by Commission Regulation (EU) 2016/128, and medical devices according to Regulation (EU) 745/2017.

The mixture M of the present invention comprises or, alternatively, consists of: I) medium-chain triglycerides- MCT, ii) omega-3 powder, titrated in DHA-docosahexaenoic acid, from about 10% to 15%, and titrated in EPA-eicosapentaenoic acid, from about 1% to about 3%, microencapsulated from fish oil; and ill) a choline bitartrate.

Preferably, the mixture comprises or, alternatively, consists of I) medium-chain triglycerides-MCTs and ii) omega-3, preferably in the form of omega-3 DHA:EPA=4:1, in a weight ratio from 1 :10 to 10:1, preferably from 1 :7 to 7:1, more preferably from 1 :5 to 5:1, e.g., 1 :1.

Preferably, the mixture comprises or, alternatively, consists of ill) choline, preferably in the form of choline bitartrate, and ii) omega-3, preferably in the form of omega-3 DHA:EPA=4:1, in a weight ratio from 1 :10 to 10:1, preferably from 1 :5 to 5:1, more preferably from 1 :2.5 to 2.5:1, e.g. 1 :1. Preferably, medium-chain triglycerides MTC may, preferably, be in the form of a dry extract titrated, for example, at 50%, or 60%, or 70%, or 80%.

Preferably, choline may be present, preferably, in the form of choline bitartrate, for example, choline bitartrate at 30%, or 35%, or 40%, or 45%, or 50%, or 55%, or 60%, or 70%.

For example, for 100 g of final composition, one can have a mixture that comprises 40 g of MCT dry extract titrated at 70% (of which 28 g of medium-chain triglycerides MCT), 30 g of omega-3 DHA:EPA=4:1 (about 5 g of omega-3), and 5 g of choline bitartrate 40% (2 g of choline).

In a preferred embodiment, the mixture M, comprising or, alternatively, consisting of: I) medium-chain triglycerides-MCT, ii) omega-3 powder, titrated in DHA -docosahexaenoic acid, from about 10% to 15%, and in to EPA -eicosapentaenoic acid, from about 1% to about 3%, microencapsulated from fish oil, and ill) a choline bitartrate, as an example of a choline source, comprises, in addition, a zinc (II) source, preferably a zinc gluconate having, for example, a CAS No. 4468-02-4, and an iron (III) source, preferably an iron pyrophosphate having, for example, a CAS No. 10058-44-3. Said zinc gluconate may, for example, have a zinc (II) content from 10% to 15%, e.g., about 13%, while said iron pyrophosphate may, for example, have an iron (III) content from 80 mg/g to 90 mg/g, e.g., 85 mg/g, and may be emulsified with lecithin, maltodextrin, and sodium chloride, and be in micronized form. This mixture is referred to as M*.

Preferably, said medium-chain triglycerides-MCT are obtained from a plant of the Arecaceae family such as, for example, from Elaeis guineensis Jacq. also known as the oil palm. Preferably, said MCT are supported in a carrier that may contain, for example, a sodium caseinate, in an amount by weight from about 20% to about 30%, a glycerol acid ester, in an amount by weight from about 2% to about 10%, and a silicon dioxide, in an amount by weight less than about 2%. Preferably, a composition of said medium-chain triglycerides may contain MCT in an amount by weight from about 70% to about 90%; a caprylic acid in an amount by weight from about 50% to about 70%; and a capric acid in an amount by weight from about 35% to about 45%; preferably said composition may have, for example, an acidity value of less than 1 mg KOH/g, a peroxide index of less than 0.13 mEq O2/Kg, a solubility in water, and a density from about 0.35 g/ml to about 0.55 g/ml; preferably said composition may have a particle size of the type 90% at 60 mesh.

Preferably, said microencapsulated omega-3 powder from fish oil is titrated at about 12% in DHA and about 3% in EPA, more preferably it is tuna oil in the presence of glucose syrup, milk protein, sodium ascorbate (E301), sodium citrate (E331) and mono and diglycerides of fatty acids (E471). Preferably, said microencapsulated omega-3 powder from fish oil may have, for example, a pH value in the range from 7.3 to 8.3; a peroxide value of less than about 2 mEq/Kg; and a solubility index greater than about 99%; more preferably, said microencapsulated omega-3 powder from fish oil may have, for example, a protein content in an amount by weight from about 6.5 to about 9 g/100 g; a fat content in an amount by weight from about 47% to about 54% g/100 g; a trans acids content in an amount by weight less than about 0.5 g/100 g TG; a DHA content in an amount by weight greater than about 120 mg/g TG; and an EPA content in an amount by weight less than about 30 mg/ g TG. Said omega-3 fatty acids are present in the mixture M in a DHA:EPA ratio of about 4:1.

Preferably, said choline is present in the mixture preferably in the form of choline bitartrate having, e.g., a CAS No. 87-67-2, and is presented as a white crystalline powder.

Preferably, said mixture M comprises, in addition to i), ii) and iii), also iv) at least one vitamin of the B group selected from the group comprising or, alternatively, consisting of:

- a vitamin B1, preferably a vitamin B1 in the form of thiamine hydrochloride having, for example, a CAS No.

67-03-8;

- a vitamin B2, preferably a vitamin B2 in the form of riboflavin having, for example, a CAS No. 83-88-5;

- a vitamin B3, preferably a vitamin B3 (or vitamin PP or niacin) in the form of nicotinamide having, for example, a CAS No. 98-92-0;

- A vitamin B5, preferably a vitamin B5 in the form of D-calcium pantotheate having, for example, a CAS No. 137-08-6;

- a vitamin B6, preferably a vitamin B6 in the form of pyridoxine hydrochloride having, for example, a CAS No. 58-56-0;

- a vitamin B8, preferably a vitamin B8 (or vitamin H or biotin) in the form of D-biotin having, for example, a CAS No. 58-85-5;

- a vitamin B9, preferably a vitamin B9 in the form of folic acid having, for example, a CAS No. 59-30-3;

- a vitamin B12, preferably a vitamin B12 in the form of cyanocobalamine having, for example, a CAS No.

68-19-9.

Preferably, said mixture M also comprises, in addition to i), ii) and iii), also said vitamin B5 and said vitamin B6, or said vitamins B5, B6, B9 and B12 to give a mixture M1.

Preferably, said mixture M or M1 comprises, in addition to i), ii), iii) and iv), also v) at least one vitamin of the C group, preferably a vitamin C in the form of (+) ascorbic acid having, for example, CAS No. 50-81-7, to give a mixture M2.

Preferably, said mixture M or M* or M1 or M2 comprises, in addition to i), ii), iii), iv) and v), also vi) at least one vitamin of the D group, preferably a vitamin D3 in the form of cholecalciferol having, for example, a CAS No. 6797-0, to give a mixture M3.

Preferably, said mixture M or M* or M1 or M2 or M3 comprises, in addition to i), ii), iii), iv), v) and iv), also vii) at least one vitamin of the E group, preferably a vitamin E in the form of DL-a-tocopheryl acetate having, for

RECTIFIED SHEET (RULE 91 ) ISA/EP example, a CAS No. 7695-91-2, to give a mixture M4.

Preferably, said mixture M or M* or M1 or M2 or M3 or M4 comprises, in addition to i), ii), iii), iv), v), vi), and vii), also viii) at least one vitamin of the K group, preferably a vitamin K1 having, for example, a CAS No. 81818-54-4, to give a mixture M5.

Preferably, said mixture M or M* or M1 or M2 or M3 or M4 or M5 comprises, in addition to i), ii), iii), iv), v), vi), vii) and viii), also ix) a source of zinc (II), preferably a zinc gluconate having , e.g. , a CAS No. 4468-02-4; said zinc gluconate may, for example, have a zinc (II) content from 10% to 15%, e.g., about 13%, and x) an iron (III) source, preferably an iron pyrophosphate having, for example, a CAS No. 10058-44-3; said iron pyrophosphate may, for example, have an iron (III) content from 80 mg/g to 90 mg/g, e.g., 85 mg/g, and may be emulsified with lecithin, maltodextrin and sodium chloride, and be in micronized form, to give a mixture M6.

Preferably, said mixture M or M* or M1 or M2 or M3 or M4 or M5 or M6 comprises, in addition to i), ii), iii), iv), v), vi), vii), viii), ix), and x), also xi) a source of potassium (I), preferably a potassium citrate having, for example, a No. CAS 6100-5-6; said potassium citrate may, for example, be present in the form of tripotassium citrate monohydrate, and xii) a source of calcium (II) and phosphorus, preferably a tricalcium phosphate having, for example, a CAS No. 12167-74-7, to give a mixture M7.

Preferably, said mixture M or M* or M1 or M2 or M3 or M4 or M5 or M6 or M7 comprises, in addition to i), ii), iii), iv), v), vi), vii), viii), ix), x), and xi), also xii) a source of magnesium (II), preferably a magnesium citrate having, for example, a No. CAS 153531-96-5; said magnesium citrate may, for example, have a magnesium (II) content from 12% to 18%, e.g., about 15% on a dry base, to give a mixture M8.

Preferably, said mixture M or M* or M1 or M2 or M3 or M4 or M5 or M6 or M7 or M8 comprises, in addition to i), ii), iii), iii), iv), v), vi), vii), viii), ix), x), xi), and xii):

- xiii) a source of manganese (II), preferably a manganese gluconate having, for example, a CAS No. 6485- 39-8; said manganese gluconate may, for example, have a manganese (II) content from10% to 15%, e.g., 12%; and/or

- xiv) a source of copper (II), preferably a copper sulfate having, for example, a CAS No. 7758-98-7; and/or

- xv) a source of potassium (I), preferably a potassium iodide having, for example, a CAS No. 7681-11-0; said potassium iodide may, for example, have an iodine (I) content from 70% to 80%, e.g., 75%; and/or

- xvi) a source of molybdenum (VI), preferably a sodium molybdate di-hydrate; said sodium molybdate may, for example, have a molybdenum (VI) content from 2% to 6%, e.g. 4%, and be supported in maltodextrins; and/or

- xvii) a source of selenium, preferably a L-seleniomethionine having, for example, a selenium content from 0.5% to 2%, e.g., 1.5%; and/or

- xviii) a source of chromium (III), preferably a chromium picolinate having, for example, a CAS No. 14639- 25-9, all to give a mixture M9.

It is an object of the present invention a solid composition comprising a solid mixture selected from the above-described mixtures M or M* or M1 or M2 or M3 or M4 or M5 or M6 or M7 or M8 or M9 and, optionally,

RECTIFIED SHEET (RULE 91 ) ISA/EP at least one additive, excipient, carrier or a flavoring substance, synthetic or natural, of food or pharmaceutical grade, to give a composition CM or CM* or CM1 or CM2 or CM3 or CM4 or CM5 or CM6 or CM7 or CM8.

Preferably, said solid compositions are in the form of microgranules, granules, or powders.

Preferably, said additive or excipient or carrier or flavor of food or pharmaceutical grade is selected from the group comprising or, alternatively, consisting of:

- a maltodextrin, preferably a maltodextrin having, for example, a CAS No. 9050-36-6;

- a vanilla flavor, preferably a powder vanilla flavor;

- a sucralose, preferably a sucralose having, for example, a CAS No. 56048-13-2;

- a silicon dioxide, preferably a silicon dioxide having, for example, a CAS No. 112926-00-8;

- citric acid, preferably citric acid having, for example, CAS No. 77-92-9.

Preferably, said compositions are useful in a preventive treatment in which said composition is preferably administered in a daily dose ranging from 10 g to 30 g, more preferably in a 20 g dose in a single-dose format as a granulate for oral use.

- a vanilla flavor, preferably a powder vanilla flavor;

- citric acid, preferably citric acid having, for example, a CAS No. 77-92-9.

The composition comprises said mixture in an amount by weight from 60% to 90%, preferably from 70% to 80%, and said additive or excipient or carrier in an amount by weight from 40% to 10%, preferably from 30% to 20%, with respect to the total weight of the composition.

Both the mixture and the composition, that comprises said mixture, are prepared using equipment and techniques known to the person skilled in the art belonging to the field of pharmaceutical, nutraceutical and dietary supplement preparations.

EXAMPLE

Per 100 g of composition, the mixture may comprise:

- i) 50 g of a dry extract titrated at 60% of MCT (Medium Chain Triglycerides) comprising 30g of MTC;

- ii) 25 g of omega-3 DHA:EPA=4:1 of which 3.9 g of omega-3; and

- iii) 5 g of choline bitartrate at 50% of which 2.5 g of choline.

A study conducted by the Applicant concerning the following protocol is in progress.

Subject: protocol for in vitro study of synergistic effect among the components of the claimed solid mixture for oral use. Specifically, the mixture comprises or, alternatively, consists of i) medium-chain triglycerides- MCT; ii) omega-3 powder, titrated in DHA-docosahexaenoic acid, from about 10% to 15%, and titrated in EPA-eicosapentaenoic acid, from about 1% to about 3%, microencapsulated from fish oil; and ill) a choline bitartrate.

The study was set up to provide for the evaluation of the impact of the mixture and its components on cellular energy metabolism. It is, therefore, an in vitro study of evaluation of the synergistic effect among the mixture components by analyzing cellular energy metabolism in the presence of the individual components and the complete mixture.

The formulations under study are: - control; - MTCs; - Omega-3 DHA:EPA; - choline (e.g. as choline bitartrate; - Mixture of: MTCs, Omega-3 DHA:EPA, choline (e.g. as choline bitartrate).

Project plan

The SH-SY5Y neuroblastoma cell model was used for the study.

The activity includes:

1 . SH-SY5Y CELL MODEL SETUP

Culture and management of the SH-SY5Y cell model in preparation for the task;

2. DISPERSION/SOLUBILIZATION OF COMPONENTS AND MIXTURES IN CELL MEDIUM

Dispersion/solubilization of samples in the most suitable medium to avoid precipitation or floating of substances during cells processing (e.g. DMSO);

3. DETERMINATION OF THE MAXIMUM NON-TOXIC CONCENTRATION FOR ALL SUBSTANCES

A dose-response at increasing concentrations of the components and mixture was performed in order to identify the maximum nontoxic concentration for each component and mixture. Based on the maximum nontoxic concentration value identified for each element, having to evaluate the synergistic effect, a common concentration was defined for all components and mixture that was used for the subsequent evaluation of the impact on cellular energy metabolism;

4. STUDY OF EFFECT OF INDIVIDUAL COMPONENTS AND MIXTURES ON CELL ATP PRODUCTION The impact of each component and mixture on cell ATP production was evaluated.

Preliminary results indicate the effectiveness of the mixture of the present invention.

Claims

1 . A solid mixture for oral use comprising or, alternatively, consisting of:

- medium-chain triglycerides-MCT;

- omega-3 powder, titrated in DHA -docosahexaenoic acid, from about 10% to 15%, and titrated in EPA - eicosapentaenoic acid, from about 1 % to about %3, microencapsulated from fish oil; and

- a choline bitartrate; said mixture being for use in a preventive method of treatment of a subjective memory disorder, a mild cognitive decline (MCI), a dementia or an Alzheimer's disease.

2. The mixture for use according to claim 1 , wherein said mixture further comprises a source of zinc (II), preferably in the form of zinc gluconate, and a source of iron (III), preferably in the form of iron pyrophosphate.

3. The mixture for use according to claim 1 or 2, wherein said mixture further comprises at least one vitamin of the B group selected from the group comprising or, alternatively, consisting of:

- a vitamin B1 , preferably a vitamin B1 in the form of thiamine hydrochloride having preferably a CAS No. 67-03-8;

- a vitamin B2, preferably a vitamin B2 in the form of riboflavin having preferably a CAS No. 83-88-5;

- a vitamin B3, preferably a vitamin B3 (or vitamin PP or niacin) in the form of nicotinamide having preferably a CAS No. 98-92-0;

- a vitamin B5, preferably a vitamin B5 in the form of D-calcium pantotheate having preferably a CAS No. 137-08-6;

- a vitamin B6, preferably a vitamin B6 in the form of pyridoxine hydrochloride having preferably a CAS No. 58-56-0;

- a vitamin B8, preferably a vitamin B8 (or vitamin H or biotin) in the form of D-biotin having preferably a CAS No. 58-85-5;

- a vitamin B9, preferably a vitamin B9 in the form of folic acid having preferably a CAS No. 59-30-3;

- a vitamin B12, preferably a vitamin B12 in the form of cyanocobalamine having preferably a CAS No. 68- 19-9.

4. The mixture for use according to any one of claims 1-3, wherein said mixture further comprises at least one vitamin of the C group, preferably a vitamin C in the form of (+) ascorbic acid having preferably a CAS No. 50-81-7.

5. The mixture for use according to any one of claims 1-4, wherein said mixture further comprises at least one vitamin of the D group, preferably a vitamin D3 in the form of cholecalciferol having preferably a CAS No. 67-97-0.

6. The mixture for use according to any one of claims 1-5, wherein said mixture further comprises at least one vitamin of the E group, preferably a vitamin E in the form of DL-a-tocopheryl acetate having preferably a CAS No. 7695-91-2.

7. The mixture for use according to any one of claims 1-6, wherein said mixture further comprises at least

RECTIFIED SHEET (RULE 91 ) ISA/EP one vitamin of the K group, preferably a vitamin K1 having preferably a CAS No. 81818-54-4.

8. The mixture for use according to any one of claims 1-7, wherein said mixture further comprises a source of potassium (I), preferably in the form of potassium citrate.

9. The mixture for use according to any one of claims 1-8, wherein said mixture further comprises a source of calcium (II) and phosphorus, preferably in the form of tricalcium phosphate.

10. The mixture for use according to any one of claims 1-9, wherein said mixture further comprises a source of magnesium (II), preferably in the form of magnesium citrate.

11. The mixture for use according to any one of claims 1-10, wherein said mixture further comprises a source of manganese (II), preferably in the form of manganese gluconate.

12. The mixture for use according to any one of claims 1-11 , wherein said mixture further comprises a source of copper (II), preferably in the form of copper sulfate.

13. The mixture for use according to any one of claims 1-12, wherein said mixture further comprises a source of iodine (I), preferably in the form of potassium iodide.

14. The mixture for use according to any one of claims 1-13, wherein said mixture further comprises a source of molybdenum (VI), preferably in the form of sodium molybdate.

15. The mixture for use according to any one of claims 1-14, wherein said mixture further comprises a source of selenium, preferably in the form of L-seleniomethionine.

16. The mixture for use according to any one of claims 1-15, wherein said mixture further comprises a source of chromium (III), preferably in the form of chromium picolinate.

17. The mixture for use according to any one of claims 1-16, wherein said mixture is preferably in the form of a powder or granules for oral use.

18. The mixture according to any one of claims 1-17, wherein said mixture comprises or, alternatively, consists of i) medium-chain triglycerides-MCT and ii) omega-3, preferably in the form of omega-3 DHA:EPA=4:1, in a weight ratio from 1 :10 to 10: 1 , preferably from 1 :7 to 7:1, more preferably from 1:5 to 5:1 , e.g., 1 :1.

19. The mixture according to any one of claims 1-18, wherein said mixture comprises or, alternatively, consists of iii) choline, preferably in the form of choline bitartrate, and ii) omega-3, preferably in the form of omega-3 DHA:EPA=4:1, in a weight ratio from 1 :10 to 10:1 , preferably from 1 :5 to 5:1 , more preferably from 1 :2.5 to 2.5: 1, e.g. 1 :1.

20. A solid composition for oral use comprising a solid mixture according to any one of claims 1-19 and optionally at least one additive, excipient, carrier or flavoring substance, synthetic or natural, of food or pharmaceutical grade.

21. The composition according to claim 20, wherein said additive or excipient or carrier or flavor of food or pharmaceutical grade is selected from the group comprising or, alternatively, consisting of:

- a maltodextrin, preferably a maltodextrin having preferably a CAS No. 9050-36-6;

- a vanilla flavor, preferably a powder vanilla flavor;

- a sucralose, preferably a sucralose having preferably a CAS No. 56048-13-2;

RECTIFIED SHEET (RULE 91 ) ISA/EP - a silicon dioxide, preferably a silicon dioxide having preferably a CAS No. 112926-00-8;

- citric acid, preferably citric acid having preferably a CAS No. 77-92-9.

22. The composition for use according to claim 20 or 21, wherein said treatment is preferably a preventive treatment.

23. The composition for use according to any one of claims 20-22, wherein said composition is preferably in the form of a powder or granules for oral use.

24. The composition for use according to any one of claims 20-23, wherein said composition is preferably administered in a daily dose ranging from 10 g to 30 g, preferably 20 g in a single-dose format as a granulate for oral use.