Nutritional composition for stroke

Abstract

The present invention relates to a nutritional composition for use in the treatment of stroke, preferably ischemic stroke, comprising a combination of (i) coenzyme Q10 and (ii) vitamin D and (iii) vitamin B2. The invention also relates to a composition comprising coenzyme Q10 and vitamin D and vitamin D3 in combination with a polyunsaturated fatty acid optionally selected from DHA, EPA and / or DPA and / or choline, choline salts and / or choline esters.

Description

Technical Field

[0001] The present invention is in the field of compositions and nutritional compositions for use in treating the consequences of a stroke, preferably an ischemic stroke. The present invention further relates to reducing the risk of recurrent stroke. Background Art

[0002] A stroke, also known as a cerebrovascular accident (CVA), is a rapid loss of brain function caused by an interruption in the blood supply to the brain. The World Health Organization (WHO) defines a stroke as "rapidly developing clinical signs of a focal (or global) disturbance of brain function, with symptoms lasting 24 hours or longer, or leading to death, with no apparent cause other than that of a vascular origin". A stroke can occur when adequate blood flow to a part of the brain is blocked, causing ischemia (lack of blood flow), usually caused by a blood clot or other embolus that lodges or forms in one of the blood vessels supplying the brain, resulting in an ischemic stroke, or when a blood vessel bursts (or ruptures), as occurs in a hemorrhagic stroke.

[0003] Brain ischemia (brain ischemia / cerebral ischemia) is a kind of result disease that causes the blood flow to the brain to be insufficient to meet metabolic needs. Ischemia can be focal ischemia, which is limited to a specific area of ​​the brain, or it can be global ischemia, covering a wide area of ​​brain tissue. If the blockage of ischemic stroke is not resolved quickly, ischemia may cause cerebral hypoxia, thereby causing permanent neurological damage or death. The consequences of stroke may be devastating, including impaired motor skills, impaired vision and language disorders. For example, the most common cause of ischemic stroke is occlusion of the middle cerebral artery (intracranial artery downstream of the internal carotid artery), which damages the brain (e.g., cerebral cortex), such as the motor and sensory cortex of the brain. This damage may cause hemiplegia, hemisensory loss and language or visual spatial defects depending on the damaged cerebral hemisphere.

[0004] Despite advances in treatment, stroke remains the leading cause of death and disability worldwide, with one in seven individuals suffering a stroke in their lifetime, and ischemic stroke accounting for more than 80% of strokes (Lackland et al., 2014). Effective treatments after stroke include reperfusion therapy, such as with recombinant tissue plasminogen activator; but this must be administered within a limited time window (within 4.5 hours of stroke onset); therefore, only 2%-4% of patients benefit from it (Hankey, 2017). Disability after stroke can impose a serious social and economic burden; few people recover spontaneously, and many people are disabled for life (Koh and Park, 2017). Traditional rehabilitation is often almost ineffective (Feigin et al., 2017), and the lack of functional recovery is partly attributed to the regeneration of central nervous system neurons and the limitations of neuroplasticity (Walmsley, AR and Mir, AK (2007) Current pharmaceutical design [Current drug design] 13: 2470-2484).

[0005] It is further believed that many nutrients are related to supporting brain and nerve function. WO 2019 / 074617 relates to a multi-nutrient composition for enhancing human nerve function by promoting outgrowth of neurites. The multi-ingredient composition comprises high levels of vitamin K2 and, in particular, coenzyme Q10, vitamin D3, cholecalciferol or ergocalciferol and phosphatidylcholine.

[0006] Fernandez-Vega et al., Nutrients, 2020, relates to nutritional supplementation with different individual supplements for treating vascular occlusive diseases affecting the retina, including supplements of coenzyme Q10 (100 mg / day) and vitamin B2 (0.7 mg vitamin B2 and 25 mg coenzyme Q10 / day), but does not disclose a nutritional composition comprising a combination of coenzyme Q10 with both vitamin D and vitamin B2 for treating the consequences of stroke.

[0007] WO 02 / 28379 A2 describes compositions and methods for reducing human plasma lipoprotein (a) (Lp(a)) and reducing risk factors for a wide range of cardiovascular diseases. However, there is a lack of explicit disclosure of any combination of nutrients for use in treating stroke.

[0008] WO 2019 / 165222 A1 describes a nutritional supplement of coQ10, vitamin B and vitamin D designed to support renal and cardiac function and mitochondrial energy function requirements in patients undergoing hemodialysis, but does not disclose treatment of (the consequences of) stroke.

[0009] US2014 / 314731 A1 describes a composition consisting of vitamin C, L-glutamine, L-cystine or L-cysteine, riboflavin, succinic acid, fumaric acid, coenzyme Q10 and niacin, and the use of the composition for minimizing the cell-damaging effects of free radicals and harmful forms of oxygen, in particular oxygen free radicals or reactive oxygen species.

[0010] Chelluboina Barrath et al. Neurochemistry international, 2020, disclosed the therapeutic potential of nutritional supplements to protect the brain after stroke, but did not disclose the use of any specific combination of nutritional supplements.

[0011] EP 2938350 A1 discloses that the underlying cause of stroke is hypercholesterolemia, which can be prevented by providing a formulation capable of lowering LDL cholesterol blood levels, improving total cholesterol blood levels, increasing HDL blood levels, lowering triglyceride blood levels and / or lowering systolic blood pressure. The formulation comprises coenzyme Q10, fish oil containing eicosapentaenoic acid and docosahexaenoic acid, and vitamin D3.

[0012] The ability of the damaged central nervous system (CNS) to regenerate after a stroke is limited, and thus there remains a continuing need in the art to find alternative approaches to treat and promote recovery after a stroke. Summary of the invention

[0013] The inventors were surprised to find that the composition comprising a therapeutically effective amount of a combination of coenzyme Q10, vitamin D and vitamin B2 can effectively treat stroke, particularly ischemic stroke. The treatment of stroke includes the treatment of the consequences of stroke. In an in vitro model, it was found that the composition comprising a combination of coenzyme Q10 and vitamin D, a combination of coenzyme Q10 and vitamin B2, and a combination of coenzyme Q10, vitamin D and vitamin B2 resulted in an increase in the outgrowth of neurites of surviving neurons after hypoxia and a reduction in neuronal damage after hypoxia compared to the situation in which there was no composition comprising a combination of coenzyme Q10 and vitamin D and / or vitamin B2. It was further observed that the combination of coenzyme Q10 and vitamin D together with vitamin B2, B6 or B9 showed a beneficial improvement in the outgrowth of neurites after hypoxia. (i) Coenzyme Q10 with (ii) vitamin D and (iii) vitamin B2, together with (iv) polyunsaturated fatty acids and (v) choline, preferably a combination of phosphatidylcholine, also beneficially increased the outgrowth of neurites of surviving neurons after hypoxia and reduced neuronal damage.

[0014] Therefore, the present invention relates to a method for treating a stroke in a subject, preferably wherein the stroke is an ischemic stroke, the method comprising administering a composition according to the present invention to the subject. The present invention also relates to a composition comprising a combination of (i) coenzyme Q10, (ii) vitamin D and (iii) vitamin B2. In one embodiment, the composition comprises a combination of coenzyme Q10, vitamin D and vitamin B2 and a combination of one or more of vitamins B6 and B9. The composition optionally further comprises (iv) polyunsaturated fatty acids and (v) choline. Therefore, the present invention also relates to a composition comprising a combination of (i) coenzyme Q10, (ii) vitamin D, (iii) vitamin B2, (iv) polyunsaturated fatty acids and (v) choline. Preferably, the composition according to the present invention further comprises one or more selected from vitamins A, B, C and E, phospholipids, selenium and magnesium. In another preferred aspect, the composition according to the present invention comprises a combination of coenzyme Q10, vitamin D, vitamin B2, polyunsaturated fatty acids, choline and one or more additional B vitamins.

[0015] According to one embodiment, the present invention relates to a method for treating a stroke in a subject, preferably wherein the stroke is an ischemic stroke, the method comprising administering to the subject a composition according to the present invention. The present invention may also be expressed as the use of a therapeutically effective combination of (i) Coenzyme Q10 with (ii) Vitamin D and (iii) Vitamin B2 in the manufacture of a composition for treating a stroke in a subject, preferably an ischemic stroke. In another embodiment, the present invention may be expressed as the use of a therapeutically effective combination of Coenzyme Q10, Vitamin D and Vitamin B2 with one or more of Vitamins B6 and B9 in the manufacture of a composition for treating a stroke in a subject, preferably an ischemic stroke. In addition, the present invention relates to the use of a therapeutically effective combination of (i) Coenzyme Q10 with (ii) Vitamin D and (iii) Vitamin B2 and optionally (iv) polyunsaturated fatty acids and (v) choline in the manufacture of a composition for treating a stroke in a subject, preferably an ischemic stroke. In other words, the present invention relates to a composition for use in treating a stroke in a subject, preferably wherein the stroke is an ischemic stroke, comprising (i) Coenzyme Q10 in combination with (ii) Vitamin D and (iii) Vitamin B2, and optionally further comprising (iv) polyunsaturated fatty acids and / or (v) choline.

[0016] In an embodiment, the present invention particularly relates to the treatment or prevention of the consequences of a stroke (preferably ischemic stroke), which relates to an improvement (e.g., increase) in the neurite length of a treated subject compared to a subject not treated with a composition according to the present invention. In some embodiments, the treatment of a stroke (preferably ischemic stroke) further relates to neuroprotection after a stroke. In some embodiments, the present invention particularly relates to the treatment or prevention of the consequences of a stroke (preferably ischemic stroke), which relates to preventing or improving the functional consequences of a stroke, such as, but not limited to, hemiplegia, hemisensory loss, language, or visual-spatial deficits.

[0017] The present invention further relates to preventing or reducing a patient's risk of a second or recurrent stroke, since patients who suffer a first stroke ("first stroke") are at increased risk of suffering another stroke during their lifetime. Within 5 years of a stroke, 24% of women and 42% of men will experience a recurrent stroke. Recurrent strokes generally have higher rates of mortality and disability, since the part of the brain that has been damaged by the original stroke may not be as resilient.

[0018] In a preferred embodiment, administration or use of the composition begins after a stroke occurs or has been diagnosed, and administration or use of the composition continues for a period of at least 2 weeks.

[0019] In a further preferred embodiment, the composition according to the invention provides a daily supplement of 5 to 90 mg of coenzyme Q10 with 5 to 80 μg of vitamin D, preferably vitamin D3, and 0.8 to 7.6 mg of vitamin B2.

[0020] Figure List

[0021] The present invention will be discussed in more detail below with reference to the accompanying drawings.

[0022] Figure 1 . The effects of coenzyme Q10, vitamin D3, vitamin B2 and their combination on neurite outgrowth in primary neurons after hypoxia are shown. Neurite outgrowth is expressed as a percentage relative to the control (100%).

[0023] Figure 2 . The effects of coenzyme Q10, vitamin D3, vitamin B6, vitamin B9 and their combination on neurite outgrowth in primary neurons after hypoxia are shown. Neurite outgrowth is expressed as a percentage relative to the control (100%).

[0024] Figure 3 Effects of Coenzyme Q10, Vitamin D3, Vitamin B2, PUFA and choline sources and their combinations on neurite outgrowth in an in vitro PC12 neuronal cell model. Neurite outgrowth is expressed as a percentage relative to the control (100%).

[0025] Figure 4 Effects of different ratios of choline chloride and phosphatidylcholine on neurite outgrowth in an in vitro PC12 neuronal cell model. Neurite outgrowth is expressed as a percentage relative to the control (100%).

[0026] List of Preferred Embodiments

[0027] 1. A nutritional composition for use in the treatment of stroke, preferably ischemic stroke, comprising a combination of (i) coenzyme Q10, (ii) vitamin D and (iii) vitamin B2.

[0028] 2. The nutritional composition for use according to embodiment 1, wherein the composition further comprises (iv) polyunsaturated fatty acids and (v) choline, preferably (iv) polyunsaturated fatty acids selected from DHA, EPA and / or DPA and (v) choline.

[0029] 3. The nutritional composition for use according to any one of embodiments 1 and 2, wherein choline is provided in the form of free choline, a choline salt and / or a choline ester, wherein the choline ester is preferably phosphatidylcholine.

[0030] 4. The nutritional composition for use according to any one of embodiments 1 to 3, wherein the composition further comprises one or more of (vi) vitamin B6 and (vii) vitamin B9.

[0031] 5. The nutritional composition for use according to any one of embodiments 1 to 4, wherein the treatment of stroke comprises treating and / or preventing consequences associated with said stroke in a subject having suffered a stroke.

[0032] 6. The nutritional composition for use according to any of the preceding embodiments, wherein the treatment of stroke comprises an increase in the length of neurite outgrowth of neurons in a subject having stroke and treated with the composition compared to a subject having stroke and not treated with the composition.

[0033] 7. The nutritional composition for use according to any of the preceding embodiments, wherein the treatment of stroke comprises preventing or ameliorating functional consequences associated with stroke selected from any of hemiplegia, hemi-esthesia, language, or visuospatial deficits, and wherein the functional consequences associated with stroke are improved in subjects treated with the composition compared to subjects who had stroke and were not treated with the composition.

[0034] 8. The nutritional composition for use according to any one of the preceding embodiments, wherein the composition is used for at least 2 weeks, preferably at least 4 weeks after diagnosis of stroke.

[0035] 9. The nutritional composition for use according to any one of the preceding embodiments, wherein the composition comprises a daily dose of:

[0036] (i) 8 to 80 mg, preferably 10 to 70 mg, more preferably 15 to 60 mg coenzyme Q10;

[0037] (ii) 6 to 75 μg, preferably 8 to 70 μg, more preferably 10 to 65 μg vitamin D, preferably vitamin D3;

[0038] (iii) Vitamin B2 in the range of 0.8 to 7.6 mg, preferably 1 to 7.4 mg, more preferably 1.2 to 7.2 mg

[0039] and optionally

[0040] (iv) 150 to 1200 mg, preferably 200 to 1100 mg, more preferably 250 to 1000 mg DHA; and / or

[0041] 300 to 2400 mg, preferably 400 to 2200 mg, more preferably 500 to 2000 mg / day of EPA; and / or

[0042] (v) 200 to 1400 mg, preferably 300 to 1200 mg, more preferably 350 to 1100 mg choline.

[0043] 10. The nutritional composition for use according to any one of the preceding embodiments, further comprising one or more selected from vitamins A, C and E, phospholipids, selenium, magnesium and additional B vitamins.

[0044] 11. The nutritional composition for use according to any one of the preceding embodiments, wherein the composition comprises v a ) phosphatidylcholine and v b ) choline or a salt thereof, and wherein the weight ratio of phosphatidylcholine to choline is greater than 0.1.

[0045] 12. The nutritional composition for use according to the preceding embodiment, wherein the nutritional composition is a liquid nutritional composition.

[0046] 13. The nutritional composition for use according to the preceding embodiment, wherein the nutritional composition is an oral nutritional supplement or a tube feed.

[0047] 14. A liquid nutritional composition comprising a combination of:

[0048] (i) Coenzyme Q10;

[0049] (ii) vitamin D, preferably vitamin D3;

[0050] (iii) vitamin B2, and;

[0051] Optionally

[0052] (iv) a polyunsaturated fatty acid selected from DHA, EPA and / or DPA, more preferably DHA and / or EPA; and

[0053] (v) choline, choline salts and / or choline esters;

[0054] and optionally at least one of (vi) vitamin B6 and (vii) vitamin B9.

[0055] 15. The liquid nutritional composition according to embodiment 14, wherein the composition

[0056] Each 100kcal contains

[0057] (i) 1.5 to 5.5 mg coenzyme Q10;

[0058] (ii) 1.3 to 4.5 μg vitamin D, preferably vitamin D3;

[0059] (iii) 0.4 to 0.6 mg vitamin B2;

[0060] Optionally further comprising

[0061] (iv) 20 to 100 mg, preferably 25 to 90 mg, more preferably 30 to 80 mg DHA; and / or

[0062] 20 to 225 mg, preferably 60 to 200 mg, more preferably 70 to 170 mg EPA; and / or

[0063] (v) 100 to 1000 mg, preferably 200 to 800 mg, more preferably 300 to 500 mg choline, choline salts and / or choline esters

[0064] and optionally at least one of (vi) and (vii);

[0065] (vi) 0.1 to 0.5 mg vitamin B6;

[0066] (vii) 16 to 80 μg vitamin B9;

[0067] 16. The liquid nutritional composition of any one of embodiments 14 and 15, wherein the composition further comprises one or more selected from vitamin A, additional vitamins B, C, E and K, phospholipids, selenium and magnesium.

[0068] 17. The liquid nutritional composition of any one of embodiments 14 to 16, wherein the composition further comprises one or more of the following per 100 kcal:

[0069] (viii) 60 to 150 μg retinol equivalents of vitamin A;

[0070] (ix) 0.05 to 0.4 mg vitamin B1;

[0071] (x) 0.4 to 1.4 μg vitamin B12;

[0072] (xi) 12 to 40 mg vitamin C;

[0073] (xii) 1 to 5.5 mg α-TE;

[0074] (xiii) 4 to 18 μg of selenium; and

[0075] (xiv) 10 to 70 mg magnesium.

[0076] 18. The liquid nutritional composition of any one of embodiments 14 to 17, wherein the composition further comprises one or more of the following per 100 kcal:

[0077] (xv) 1 to 2.5 mg vitamin B3;

[0078] (xvi) 0.2 to 1 mg vitamin B5;

[0079] (xvii) 1.5 to 6 mg vitamin B7.

[0080] 19. The liquid nutritional composition of any one of embodiments 14 to 18, wherein the composition comprises phosphatidylcholine and choline, and wherein the weight ratio of phosphatidylcholine to choline is greater than 0.1.

[0081] 20. The liquid nutritional composition according to any one of embodiments 14 to 19, wherein the composition has a caloric density between 1.0 and 2.5 kcal / ml, preferably between 1.2 and 2.4 kcal / ml.

[0082] 21. The liquid nutritional composition according to embodiments 14 to 20, wherein the composition has 4 to 7 g protein / 100 kcal, 3 to 5.5 g lipid / 100 kcal and 8.5 to 10.5 g carbohydrate / 100 kcal. DETAILED DESCRIPTION

[0083] The present invention relates to a method for treating a stroke in a subject, preferably wherein the stroke is an ischemic stroke, wherein the method involves administering to the subject a composition comprising (i) a combination of coenzyme Q10 with (ii) vitamin D and (iii) vitamin B2, optionally further comprising (iv) polyunsaturated fatty acids and / or (v) choline, preferably (iv) polyunsaturated fatty acids and (v) choline. In an embodiment, the composition comprises a combination of coenzyme Q10 and vitamin D with a combination of one or more of vitamin B2 and B6 and B9. Preferably, the composition according to the present invention further comprises one or more selected from vitamins A, B, C and E, phospholipids, selenium and magnesium.

[0084] Alternatively, the present invention also relates to the use of a composition comprising (i) coenzyme Q10 in combination with (ii) vitamin D and (iii) vitamin B2 and optionally (iv) polyunsaturated fatty acids and / or (v) choline in the manufacture of a composition for treating a stroke, preferably an ischemic stroke, in a subject. Preferably, the composition according to the present invention further comprises one or more selected from vitamins A, B, C and E, phospholipids, selenium and magnesium.

[0085] In addition, the present invention relates to a composition for use in treating a stroke in a subject, wherein the stroke is preferably an ischemic stroke, the composition comprising a combination of (i) Coenzyme Q10 with (ii) Vitamin D and (iii) Vitamin B2 and optionally (iv) polyunsaturated fatty acids and / or (v) choline. Preferably, the composition according to the present invention further comprises one or more selected from vitamins A, B, C and E, phospholipids, selenium and magnesium. In a specific embodiment, the composition comprises a combination of Coenzyme Q10 and Vitamin D with a combination of one or more of Vitamin B2 and B6 and B9.

[0086] The present invention further particularly relates to treating stroke, more particularly treating or preventing stroke, preferably the consequences of ischemic stroke. The treatment of stroke (preferably ischemic stroke) relates to improving (e.g., increasing) the neurite length of a subject treated with a composition according to the present invention compared to a subject not treated with a composition according to the present invention. In some embodiments, the treatment of stroke (preferably ischemic stroke) further relates to neuroprotection after stroke. The treatment of stroke (preferably ischemic stroke) further includes improving the recovery of neurons after hypoxia and reducing inflammation and oxidative processes. Therefore, the treatment of stroke relates to neuronal repair or regeneration and neuronal network recovery after stroke occurs. In an embodiment, the treatment of stroke includes neuroprotection of neurons exposed to hypoxia. In an embodiment, the treatment of stroke (preferably ischemic stroke) further relates to neuronal repair and / or neuronal network recovery. In some embodiments, the present invention particularly relates to treating or preventing the consequences of stroke (preferably ischemic stroke), which relates to preventing or improving the functional consequences of stroke, such as but not limited to hemiplegia, hemisensory loss, language or visual spatial defects.

[0087] Without being bound by theory, it is believed that coenzyme Q10 is used together with vitamin D3 and vitamin B2 to beneficially alleviate oxidative damage, thereby helping to reduce the degree of neuronal damage after hypoxia. It is further believed that vitamin B6 and B9 further enhance the antioxidant capacity of coenzyme Q10 together with vitamin D3, and allow to alleviate oxidative damage and promote neuronal recovery. Polyunsaturated fatty acids then beneficially support brain metabolism, cell survival and provide anti-inflammatory effects, thereby support healing or recovery after hypoxia. Choline is related to neuroinflammation reduction, functional and structural connectivity, and has a beneficial effect on cerebral blood flow. It is believed that the composition according to the present invention provides the best promotion of outgrowth and recovery of neurites after hypoxia on the one hand, while supporting brain function.

[0088] The methods or uses according to the invention or the compositions for use according to the invention are further described in the following examples.

[0089] definition

[0090] Throughout this application, the following terms and abbreviations may be used. "Nutritional composition" means a substance or formulation that satisfies at least a portion of a subject's nutritional needs. Throughout this disclosure, the terms "nutrition," "nutritional formula," "enteral nutrition," and "nutritional supplement" are used as non-limiting examples of nutritional compositions. In addition, "nutritional composition" may refer to an enteral formula, oral formula, infant formula, pediatric subject formula, children's formula, growing-up milk, and / or adult formula in a liquid, powder, gel, paste, solid, concentrate, suspension, or ready-to-use form.

[0091] The term "supplement" or "nutritional supplement" refers to a nutritional product that provides an individual with nutrients that the individual may not otherwise be able to conveniently consume in sufficient quantities and can be used to supplement the individual's nutrition. It can be in the form of tablets, capsules, lozenges, or liquids. Supplements generally provide selected nutrients but do not represent a major part of the subject's overall nutritional needs. Typically, they do not exceed 0.1%, 1%, 5%, 10% of the subject's daily energy needs.

[0092] As used herein, "neuroprotection" refers to promoting neuronal repair, limiting neuronal oxidative stress, limiting cellular damage, and / or promoting neuronal network recovery after stroke.

[0093] "Prevention" includes reducing the risk and / or severity of neuronal damage in stroke. The terms "treatment" and "relief" include both: preventive treatment or preventive treatment (preventing targeted pathological conditions or disorders and / or slowing down their development) and curative, therapeutic or disease-modifying treatment, including curing, slowing down, alleviating the symptoms of diagnosed pathological conditions or disorders and / or stopping the treatment of their progress; and treatment is faced with the risk of suffering from the disease or suspected of having suffered from the disease, and patients who are ill or have been diagnosed with a disease or medical condition. The term does not necessarily mean that the subject is treated until fully recovered. The terms "treatment" and "relief" also refer to maintaining and / or promoting health in individuals who do not suffer from the disease but may be prone to developing unhealthy conditions. The terms "treatment" and "relief" are also intended to include strengthening or otherwise enhancing one or more primary preventive or therapeutic measures. The terms "treatment" and "relief" are further intended to include dietary management of disease or illness in subjects in need or dietary management for preventing or preventing disease or illness.

[0094] As used herein, a subject is a mammal, preferably a human.

[0095] As used herein, a "therapeutically effective amount" is an amount that alleviates symptoms, manages the progression of the consequences of a stroke, or provides a nutritional, physiological, or medical benefit to the individual.

[0096] The term "neurite" refers to the outgrowth process of a neuron. As used herein, the term neurite encompasses all such cellular processes (including both axons and dendrites) that grow outward from a neuron.

[0097] The term "neurite outgrowth" refers to the cellular process of outgrowth from a neuron, or to a cell comprising outgrowth from a neuron.

[0098] In this document and its claims, the verb "comprise" and its word form changes are used in its non-restrictive sense, meaning to include the part after the word, but not excluding the part not specifically mentioned. In addition, when used in this article, the term weight percentage (wt%) is the weight percentage based on the total weight. In addition, unless the context clearly requires the presence of one / a kind and only one / a kind of element, the possibility of referring to an element by the indefinite article "a" or "an" is not excluded that there are more than one / a kind of element. Therefore, the indefinite article "a" or "an" usually means "at least one / a kind".

[0099] Composition

[0100] The method or use according to the invention or the composition for use according to the invention involves administering a composition according to the invention. The composition according to the invention can be used as a pharmaceutical product or a nutritional product. In one embodiment, the nutritional composition of the invention is a liquid. In one embodiment, preferably, the nutritional composition of the invention is a liquid, ready-to-feed composition. Preferably, the composition is administered orally or as a tube feed.

[0101] In one aspect, the composition according to the present invention can be used as a pharmaceutical product, which includes one or more pharmaceutically acceptable carrier materials. Such a product can contain a daily dose defined as follows in one or more dosage units. The dosage unit can be in liquid form or solid form, wherein in the latter case, the daily dose can be provided by one or more solid dosage units, such as in one or more capsules or tablets. The pharmaceutical product (preferably for enteral application) can be a solid or liquid galenic formulation. Examples of solid galenic formulations are tablets, capsules (e.g., hard shell or soft shell gelatin capsules), pills, sachets, powders, granules, etc. containing active ingredients and conventional galenic carriers. Any conventional carrier material can be utilized. The carrier material can be an organic or inorganic inert carrier material suitable for oral administration. Suitable carriers include water, gelatin, gum arabic, lactose, starch, magnesium stearate, talc, vegetable oils, etc. In addition, additives such as thickeners, flavoring agents, preservatives, stabilizers, emulsifiers, buffers, etc. can be added according to the recognized practice of drug compounding. While the individual active ingredients are suitably administered in a single composition, they may also be administered in separate dosage units.

[0102] In preferred aspects, compositions according to the present invention can be used as nutritional products, for example, as nutritional supplements, for example, as additives for normal diets, as fortifiers added to normal diets, or as complete nutrition. The nutritional products preferably comprise at least one component, preferably all components, selected from the group of fat, protein and carbohydrates. It should be understood that the difference between nutritional products and pharmaceutical products is that the existence of nutrients, particularly protein, fat, digestible carbohydrates and dietary fiber, that provide nutrition for the experimenter using the composition. It can further contain ingredients such as minerals, vitamins, organic acids and flavorings. Although the term "nutritional health products" is often used in the literature, it represents a nutritional product with a pharmaceutical component or pharmaceutical purpose. Therefore, nutritional compositions according to the present invention can also be used in nutritional health products.

[0103] In one embodiment, the composition comprises a lipid portion, wherein the lipid portion provides 15% to 50% of the energy of the composition. In one embodiment, the composition is a liquid composition containing 1.1 to 2.6 kcal / ml, preferably 1.2 to 2.4 kcal / ml. In one embodiment, the composition is a tube feed with a caloric density of 1.1 to 1.7 kcal / ml, preferably 1.2 to 1.6 kcal / ml. In another embodiment, the composition is in the form of an oral nutritional supplement with a caloric density between 2.2 to 2.6 kcal / ml. The energy provided by the nutrients is calculated using the following Atwater calculation coefficients: 9 kcal / g lipid, 4 kcal / g protein or digestible carbohydrates, 2 kcal / g fiber and other components in the 0 kcal product.

[0104] The amount of the lipid fraction can be determined by applying methods known in the art for measuring the fat content in food matrices (when applicable). For example, the fat content of general foods is determined by applying AOAC (R) official method 983.23, while the Roese-Gottlieb method (AOAC (R) 932.06) is more suitable for products based on dry milk powder (Lehner, R., Estoppey, A., (1954) Mitt. Lebensmitteluntersuchung Hyg. [News on food inspection and hygiene] 54: 183-185). The amount of individual lipid components can be determined by applying methods specifically designed to measure specific components or by fractionating the fat fraction separated from the extract of the chloroform-ethanol fraction as given in the 983.23 method.

[0105] Suitable sources of lipid for use in the compositions include, but are not limited to, fish oil, krill oil, algae oil, soybean oil, rapeseed oil (such as rapeseed oil, canola oil and canola oil), high oleic sunflower oil, coconut oil, high oleic safflower oil and olive oil. Alternative selection is the lipid obtained from the milk of non-human mammals, preferably cow's milk, goat's milk, sheep's milk, horse's milk, buffalo's milk, yak's milk, reindeer's milk, donkey's milk and camel's milk, particularly cow's milk and / or goat's milk. Milk lipids are sometimes also referred to as milk fat or butter fat.

[0106] Therefore, the nutritional composition according to the invention preferably comprises a lipid fraction, preferably a lipid fraction suitable for nutrition as known in the art. The composition comprises 4 to 12 g lipid / 100 ml, preferably 4.5 to 11 g lipid / 100 ml, more preferably 5 to 10 g / 100 ml. Based on calories, preferably, the composition according to the invention may comprise 3 to 5.5 g lipid / 100 kcal, preferably 3.5 to 5 g / 100 kcal, more preferably 3.8 to 4.5 g lipid / 100 kcal, based on the total energy content of the composition. The lipid fraction comprises polyunsaturated fatty acids and optionally also monounsaturated fatty acids (MUFA) and saturated fatty acids (SFA).

[0107] The composition according to the present invention preferably comprises 4 to 17g protein / 100ml composition. The total protein present in the nutritional composition, i.e. the combination of all proteins present, can also be referred to as the "protein portion" of the nutritional composition. Therefore, the nutritional composition preferably comprises 4-17g protein portion / 100ml composition. In a preferred aspect, the nutritional composition comprises 5 to 16g protein portion / 100ml composition, more preferably 6-15g. Most preferably, the composition comprises 11 to 14.5g protein portion / 100ml composition. Based on calories, preferably, the composition according to the present invention can comprise 4 to 7g protein portion / 100kcal, preferably 4.5 to 6.5g protein portion / 100kcal, more preferably 5 to 6g protein portion / 100kcal based on the total energy content of the composition.

[0108] Suitable protein sources can be based on milk proteins (such as whey, casein, and mixtures thereof) and vegetable proteins (such as those based on soy, potato, pea, etc.). The nutritional composition preferably further comprises a carbohydrate portion. The composition preferably comprises 9 to 25 g carbohydrates / 100 ml, more preferably 10 to 24 g / 100 ml, even more preferably 11 to 23 g / 100 ml. Based on calories, preferably, the composition according to the present invention can comprise 8.5 to 10.5 g carbohydrates / 100 kcal, preferably 9 to 10 g / 100 kcal, more preferably 9.2 to 9.6 g carbohydrates / 100 kcal based on the total energy content of the composition.

[0109] Suitable carbohydrate sources include lactose, glucose, sucrose, fructose, galactose, maltose, starch, isomaltose and maltodextrin.

[0110] The composition of the present invention is typically an enteral composition, i.e. intended for oral administration, such as tube feedings, nutritional drinks and oral nutritional supplements. It is preferably administered in liquid form. Preferably, the composition comprises water in which the further components are dissolved or suspended.

[0111] Thus, the composition is preferably a liquid or a solid (typically a powder or tablet, preferably a powder) that can be reconstituted with a liquid, preferably water, to obtain a liquid composition. The dosage of the components defined below may be, for example, a daily dose or a concentration per 100 mL or 100 kcal.

[0112] Compositions according to the invention are used to treat stroke, preferably ischemic stroke. Stroke is preferably ischemic stroke, which may also be referred to as ischemic event, ischemic attack, or cerebral infarction, and treatment particularly relates to the treatment of the consequences of stroke. Treatment relates to improved outgrowth of neurites.

[0113] Compositions as described above can be used as nutritional therapy, nutritional support, medical food, food or nutritional supplements for special medical purposes. The application of the composition according to the present invention typically occurs during the recovery and / or rehabilitation period after the stroke occurs, and as long as its negative effects are extended, it can be continued. Although positive effects have been observed during the first week of application, the application is preferably continued for at least 2 weeks, more preferably at least 4 weeks, and even more preferably at least 8 weeks. Application is preferably started on the first day after the stroke occurs. The composition according to the present invention can be taken in one, two or three portions (typically 125mL per portion) of 50-250mL / day during the recovery and / or rehabilitation period after the stroke occurs in the form of a liquid composition, preferably an oral nutritional supplement. The preferred daily dose is in the range of 100 to 500mL, more preferably 125 to 375mL, most preferably 200 to 300mL. Preferably, the composition is administered enterally. It is preferably administered at least once a day, although alternative dosage regimens can be determined from these numbers. Alternatively, the composition can be a tube feed and is administered continuously. The preferred daily dose of the gavage is in the range of 1000 to 3000 kcal / day, preferably 1500 kcal to 2500 kcal / day. Preferably about 1 to 2 litres of the gavage are administered per day.

[0114] The method or use or composition for use according to the invention relates to a composition comprising a combination of (i) Coenzyme Q10 with (ii) Vitamin D and (iii) Vitamin B2, optionally further comprising (iv) polyunsaturated fatty acids and / or (v) choline. In an embodiment, the composition comprises a combination of Coenzyme Q10 and Vitamin D with a combination of one or more of Vitamin B2 and optionally B6 and B9. The composition optionally further comprises (iv) polyunsaturated fatty acids and / or (v) choline. Preferably, the composition according to the invention further comprises one or more selected from Vitamin A, additional Vitamins B, C and E, phospholipids, selenium and magnesium.

[0115] Coenzyme Q10

[0116] The composition according to the present invention comprises a therapeutically effective amount of Coenzyme Q10. In an embodiment, the composition according to the present invention comprises a combination of Coenzyme Q10 with Vitamin D and Vitamin B2. In a further embodiment, the composition according to the present invention may comprise a combination of Coenzyme Q10, Vitamin D and Vitamin B2 with a combination of one or more of Vitamins B6 and B9. In a further embodiment, the composition according to the present invention may comprise a combination of Coenzyme Q10, Vitamin D and Vitamin B2 with a combination of polyunsaturated fatty acids and / or choline.

[0117] Coenzyme Q10 (also known as CoQ10, Q10, vitamin Q10, ubiquinone, and ubidecarenone) is a benzoquinone compound synthesized naturally by the human body. The "Q" and "10" in the name refer to the quinone chemical group and the 10 isoprenyl chemical subunits, respectively, that are part of the structure of the compound. As used herein, Coenzyme Q10 refers to ubiquinone (2,3-dimethoxy-5-methyl-6-decaisoprenylbenzoquinone) and / or its functional analogs, including ubiquinol.

[0118] Coenzyme Q10 is a natural, fat-soluble substance that functions primarily as an essential enzyme cofactor in the mitochondrial electron transport chain and is a key factor in oxidative phosphorylation and aerobic cellular respiration through the generation of adenosine triphosphate (ATP) (Egil Fosslien; Mitochondrial Medicine-Molecular Pathology of Defective Oxidative Phosphorylation, Annals of Clinical and Laboratory Science, 2000).

[0119] Due to the lipid solubility of CoQ10 and its ability to exist in both a fully reduced form (ubiquinol) and a fully oxidized form (ubiquinone), it has been shown to function both as an antioxidant and as an electron carrier.

[0120] CoQ10 accepts electrons derived from Complex I (NADH ubiquinone oxidoreductase) and Complex II (succinate ubiquinone reductase) and then transports them to Complex III (ubiquinol cytochrome c reductase).

[0121] Natural sources of CoQ10 and / or analogs suitable for use in the present invention include extracts or isolates of fungi, yeast or bacteria, canola oil or soybean oil.

[0122] The composition of the present invention preferably contains 1 to 15 mg Coenzyme Q10 / 100 ml, preferably 1.5 to 14 mg Coenzyme Q10 / 100 ml, more preferably 2 to 13 mg Coenzyme Q10 / 100 ml, and even more preferably 2.5 to 12 mg Coenzyme Q10 / 100 ml composition.

[0123] According to one embodiment, Coenzyme Q10 is preferably provided in an amount of 5 to 90 mg / day, more preferably 8 to 80 mg / day, even more preferably 10 to 70 mg / day, and most preferably 15 to 60 mg / day.

[0124] In an embodiment, the composition is in the form of a gavage, and Coenzyme Q10 is preferably provided in an amount of 8 to 75 mg / day, more preferably 10 to 70 mg / day, even more preferably 15 to 65 mg / day, and most preferably 20 to 60 mg / day.

[0125] In another embodiment, when the composition is in the form of an oral nutritional supplement, Coenzyme Q10 is preferably provided in an amount of 8 to 60 mg / day, more preferably 10 to 55 mg / day, even more preferably 12 to 50 mg / day, and most preferably 15 to 45 mg / day.

[0126] Based on calories, preferably, the nutritional composition according to the present invention comprises 1.5 to 5.5 mg Coenzyme Q10 / 100 kcal, preferably 1.8 to 5.2 mg Coenzyme Q10 / 100 kcal, more preferably 2 to 5 mg Coenzyme Q10 / 100 kcal, based on the total energy content of the nutritional composition. The above figures are based on the molar weight of ubiquinone.

[0127] Vitamin D

[0128] The composition of the present invention may comprise vitamin D. In an embodiment, the composition comprises coenzyme Q10 and vitamin D. In a further embodiment, the composition according to the present invention may comprise a combination of coenzyme Q10 and vitamin D with a combination of vitamin B2 and optionally one or more of vitamins B6 and B9. In a further embodiment, the composition according to the present invention may comprise a combination of coenzyme Q10, vitamin D and vitamin B2 with a combination of polyunsaturated fatty acids and / or choline, preferably with a combination of polyunsaturated fatty acids and choline.

[0129] Vitamin D is a group of fat-soluble secosteroids, the two main physiologically relevant forms of which are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). These are collectively referred to as calciferols. Vitamin D without a subscript refers to all forms of vitamin D, D1, D2, D3 or D4, in particular D2 and D3, or any mixture thereof. The composition according to the invention preferably comprises vitamin D3.

[0130] When ingested, vitamin D is hydroxylated in the liver (endoplasmic reticulum) by the enzyme 25-hydroxylase produced by hepatocytes to 25-hydroxycholecalciferol (25(OH)D), also known as calcifediol. Once made, the product is stored in the hepatocytes until it is needed and can be released into the plasma where it will be bound to alpha-globulin. 25-hydroxycholecalciferol is then transported to the proximal tubules of the kidneys where it can be hydroxylated by one of two enzymes to different forms of vitamin D, one of which is active vitamin D (1,25(OH)2D) and the other is inactive vitamin D (24,25(OH)D). The enzyme 1α-hydroxylase, activated by parathyroid hormone (and additionally by low calcium or phosphate), forms the major biologically active vitamin D hormone, where C1 is hydroxylated to form 1,25-dihydroxycholecalciferol (1,25(OH)2D, also known as calcitriol). When 1α-hydroxylase is inactive, a separate enzyme hydroxylates the C24 atom to form 24R,25(OH)2D3, which inactivates the molecule and renders it devoid of any biological activity.

[0131] Vitamin D can be provided in active (1,25(OH)2D) or inactive (vitamin D3 or D2) forms.

[0132] The composition of the present invention preferably comprises 1.5 to 10 μg vitamin D, preferably 2 to 9 μg vitamin D / 100 ml, more preferably 2.5 to 8 μg vitamin D / 100 ml composition.

[0133] According to one embodiment, vitamin D, preferably vitamin D3, is supplemented in an amount of 5 to 80 μg / day, preferably 6 to 75 μg / day, more preferably 8 to 70 μg / day, even more preferably 10 to 65 μg / day.

[0134] In an embodiment, the composition is in the form of a gavage, and vitamin D (preferably vitamin D3) is preferably provided in an amount of 14 to 80 μg / day, more preferably 16 to 75 μg / day, even more preferably 18 to 70 μg / day, most preferably 20 to 65 μg / day.

[0135] In another embodiment, when the composition is in the form of an oral nutritional supplement, vitamin D (preferably vitamin D3) is preferably provided in an amount of 5 to 45 μg / day, more preferably 6 to 40 μg / day, even more preferably 8 to 35 μg / day, and most preferably 10 to 30 μg / day.

[0136] Based on calories, preferably, the nutritional composition according to the present invention comprises 1.3 to 4.5 μg vitamin D (preferably vitamin D3) / 100 kcal, preferably 1.5 to 4 μg vitamin D / 100 kcal, more preferably 2 to 3.5 μg / 100 kcal, based on the total energy content of the nutritional composition. The above figures are based on the molar weight of vitamin D3.

[0137] Vitamin B

[0138] The composition of the present invention may further comprise B vitamins. B vitamins are known as nutritional cofactors that act as biochemical "spark plugs" in mitochondria and therefore function to further cultivate and support optimal neural metabolism. In an embodiment, the composition comprises Coenzyme Q10 and at least Vitamin D and Vitamin B2. In a further embodiment, the composition comprises Coenzyme Q10, Vitamin D and Vitamin B2, optionally together with Vitamin B6 and / or Vitamin B9.

[0139] The composition of the present invention preferably comprises at least one B vitamin selected from the group consisting of: vitamin B1 (thiamine), B2 (riboflavin), B3 (niacin or niacinamide), vitamin B5 (pantothenic acid), B6 ​​(pyridoxine, pyridoxal, or pyridoxamine, or pyridoxine hydrochloride), vitamin B7 (biotin), vitamin B9 (folic acid or folate) and vitamin B12 (cobalamin). Functional equivalents are encompassed within these terms. The term "vitamin B12" encompasses all cobalamin equivalents known in the art.

[0140] Preferably, in the context of the composition according to the present invention, the B vitamins comprise at least one, preferably at least two, even more preferably at least three B vitamins selected from the group consisting of vitamin B1, B2, B3, B5, B6, B7, vitamin B12 and vitamin B9. More preferably, the composition comprises at least one of vitamin B2, B6 and / or B9. In a further preferred embodiment, the composition comprises vitamin B2, B6 and / or B9, preferably vitamin B2, B6 and B9, more preferably vitamin B2, B6, B9 and B12, even more preferably one or more of vitamin B1, vitamin B2, vitamin B6, vitamin B9 and vitamin B12. In one embodiment, the composition according to the present invention may comprise all of vitamin B1 (thiamine), B2 (riboflavin), B6 ​​(pyridoxine, pyridoxal or pyridoxamine or pyridoxine hydrochloride), vitamin B9 (folic acid or folate) and vitamin B12 (cyanocobalamin). In some embodiments, the composition may include additional B vitamins, as used herein, additional B vitamins are vitamins B1, B3, B5 and B7, which the composition may include in addition to one or more of vitamin B2, vitamin B6 and vitamin B9.

[0141] If present in the composition, vitamin B1 is preferably present in an amount providing a daily dose in the range of 0.7 to 5 mg, preferably in the range of 0.8 to 4.9 mg, more preferably in the range of 0.9 to 4.8 mg. When the composition is in the form of a tube feed, the daily application of vitamin B1 is preferably 1.2 to 5.5 mg / day, more preferably 1.5 to 5 mg / day, and most preferably 1.6 to 4.8 mg / day. When the composition is in the form of an oral nutritional supplement, the daily application of vitamin B1 is preferably 0.7 to 2.9 mg / day, more preferably 0.8 to 2.8 mg / day, and most preferably 0.9 to 2.7 mg / day. If present, the composition preferably comprises 0.1 to 0.9 mg vitamin B1 / 100 ml, more preferably 0.15 to 0.8 mg vitamin B1 / 100 ml, and more preferably 0.2 to 0.75 mg vitamin B1 / 100 ml. Based on calories, preferably, the nutritional composition according to the invention may comprise 0.05 to 0.4 mg vitamin B1 / 100 kcal, preferably 0.1 to 0.35 mg vitamin B1 / 100 kcal, more preferably 0.15 to 0.30 vitamin B1 / 100 kcal, based on the total energy content of the composition. The above figures are based on the molar weight of thiamine.

[0142] Vitamin B2 or riboflavin is the starting compound for the synthesis of the coenzymes flavin mononucleotide (FMN, also known as riboflavin-5'-phosphate) and flavin adenine dinucleotide (FAD). The latter coenzyme is crucially involved in energy metabolism, cellular respiration, growth and development, and a cofactor in the metabolism of essential fatty acids in brain lipids. A high proportion (>50%) of acute ischemic stroke patients are reported to be riboflavin deficient, as indicated by a high erythrocyte glutathione reductase activity coefficient (EGRAC) (Gariballa, S. et al. Eur J Clin Nutr [European Journal of Clinical Nutrition], 2007).

[0143] If present in the composition, vitamin B2 is preferably present in an amount providing a daily dose in the range of 0.8 to 7.6 mg, preferably in the range of 1 to 7.4 mg, more preferably in the range of 1.2 to 7.2 mg. When the composition is in the form of a tube feed, the daily application of vitamin B2 is preferably 2 to 7.6 mg / day, more preferably 2.2 to 7.4 mg / day, and most preferably 2.4 to 7.2 mg / day. When the composition is in the form of an oral nutritional supplement, the daily application of vitamin B2 is preferably 0.8 to 4 mg / day, more preferably 1 to 3.8 mg / day, and most preferably 1.2 to 3.6 mg / day. If present, the composition preferably comprises 0.1-1.4 mg vitamin B2 / 100 ml, more preferably 0.2-1.2 mg vitamin B2 / 100 ml, and more preferably 0.3-1 mg vitamin B2 / 100 ml. Based on calories, preferably, the nutritional composition according to the present invention may contain 0.4 to 0.6 mg vitamin B2 / 100 kcal, preferably 0.15 to 0.5 mg vitamin B2 / 100 kcal, more preferably 0.2 to 0.4 mg vitamin B2 / 100 kcal, based on the total energy content of the composition. The above figures are based on the molar weight of riboflavin.

[0144] If present in the composition, vitamin B3 is preferably present in an amount providing a daily dose of niacin equivalents in the range of 3 to 45 mg per day, preferably in the range of 3.5 to 42 mg, more preferably in the range of 3.8 to 40 mg. When the composition is in the form of a tube feed, the daily application of vitamin B3 is preferably 11 to 42 mg / day, more preferably 12 to 40 mg / day, and most preferably 12.5 to 39 mg niacin equivalents / day. When the composition is in the form of an oral nutritional supplement, the daily application of vitamin B3 is preferably 3.4 to 20 mg / day, more preferably 3.6 to 19 mg / day, and most preferably 3.8 to 18 mg niacin equivalents / day. If present, the composition preferably comprises 1.2 to 6 mg niacin equivalents / 100 ml, more preferably 1.4 to 5.5 mg niacin equivalents / 100 ml, and more preferably 1.6 to 5 mg niacin equivalents / 100 ml. Based on calories, preferably, the nutritional composition according to the present invention may contain 1 to 2.5 mg niacin equivalent / 100 kcal, preferably 1.1 to 2.2 mg niacin equivalent / 100 kcal, more preferably 1.2 to 2 mg niacin equivalent / 100 kcal, based on the total energy content of the composition. The above figures are based on the molar weight of niacin.

[0145] If present in the composition, vitamin B5 is preferably present in an amount providing a daily dose in the range of 0.8 to 15 mg, preferably in the range of 1 to 14 mg, more preferably in the range of 1.2 to 13 mg. When the composition is in the form of a tube feed, the daily application of vitamin B5 is preferably 3.5 to 14 mg / day, more preferably 4 to 13 mg / day, and most preferably 4.1 to 12.6 mg / day. When the composition is in the form of an oral nutritional supplement, the daily application of vitamin B5 is preferably 0.8 to 7.5 mg / day, more preferably 1 to 7 mg / day, and most preferably 1.2 to 6.8 / day. If present, the composition preferably comprises 0.3 to 2.2 mg vitamin B5 / 100 ml, more preferably 0.4 to 2 mg vitamin B5 / 100 ml, and more preferably 0.5 to 1.8 mg vitamin B5 / 100 ml. Based on calories, preferably, the nutritional composition according to the invention may comprise 0.2 to 1 mg vitamin B5 / 100 kcal, preferably 0.3 to 0.9 mg vitamin B5 / 100 kcal, more preferably 0.4 to 0.8 mg vitamin B5 / 100 kcal, based on the total energy content of the composition. The above figures are based on the molar weight of pantothenic acid.

[0146] The active form of vitamin B6, pyridoxal 5'-phosphate (PLP), acts as a coenzyme in multienzyme reactions of amino acid, glucose and lipid metabolism, and is known to be the rate-limiting factor in the synthesis of some neurotransmitters.

[0147] If present in the composition, vitamin B6 is preferably present in an amount providing a daily dose in the range of 0.7 to 9 mg, preferably in the range of 0.8 to 8 mg, more preferably in the range of 0.9 to 7.5 mg. When the composition is in the form of a tube feed, the daily application of vitamin B6 is preferably 1.5 to 9 mg / day, more preferably 2 to 8 mg / day, and most preferably 2.5 to 7.5 mg / day. When the composition is in the form of an oral nutritional supplement, the daily application of vitamin B6 is preferably 0.7 to 3.5 mg / day, more preferably 0.8 to 3 mg / day, and most preferably 0.9 to 2.7 mg / day. If present, the composition preferably comprises 0.2 to 1 mg vitamin B6 / 100 ml, more preferably 0.25-0.8 mg vitamin B6 / 100 ml, and more preferably 0.3 to 0.7 mg vitamin B6 / 100 ml. Based on calories, preferably, the composition according to the invention may contain 0.1 to 0.5 mg vitamin B6 / 100 kcal, preferably 0.2 to 0.4 mg vitamin B6 / 100 kcal, more preferably 0.25 to 0.3 mg vitamin B6 / 100 kcal, based on the total energy content of the composition. The above figures are based on the molar weight of pyridoxine.

[0148] If present in the composition, vitamin B7 is preferably present in an amount providing a daily dose in the range of 8 to 95 μg per day, preferably in the range of 9 to 90 μg, more preferably in the range of 9.5 to 85 μg. When the composition is in the form of a tube feed, the daily administration of vitamin B7 is preferably 24 to 95 μg / day, more preferably 26 to 90 μg / day, and most preferably 28 to 88 μg / day. When the composition is in the form of an oral nutritional supplement, the daily administration of vitamin B7 is preferably 9.4 to 45 μg / day, more preferably 9.6 to 42 μg / day, and most preferably 9.8 to 41 μg / day. If present, the composition preferably contains 2 to 14 μg vitamin B7 / 100 ml, more preferably 3 to 12 μg vitamin B7 / 100 ml, and more preferably 3.5 to 11 μg vitamin B7 / 100 ml. Based on calories, preferably, the composition according to the invention may contain 1.5 to 6 μg vitamin B7 / 100 kcal, preferably 2 to 5.5 μg vitamin B7 / 100 kcal, more preferably 2.5 to 5 μg vitamin B7 / 100 kcal, based on the total energy content of the composition. The above figures are based on the molar weight of biotin.

[0149] Vitamin B9 or folic acid is an essential nutrient that is converted to folate by the body and is required for DNA and RNA biosynthesis, DNA repair, and one-carbon metabolic reactions. Decreased folate levels are frequently reported in stroke patients and are associated with hyperhomocysteinemia, which is common in stroke patients (Poddar, R, Exp Neurol [Experimental Neurology], 2021).

[0150] If present in the composition, vitamin B9 is preferably present in an amount providing a daily dose in the range of 150 to 900 μg per day, preferably in the range of 175 to 800 μg, more preferably in the range of 200 to 750 μg. When the composition is in the form of a tube feed, the daily administration of vitamin B9 is preferably 200 to 800 μg / day, more preferably 225 to 775 μg / day, and most preferably 240 to 750 μg / day. When the composition is in the form of an oral nutritional supplement, the daily administration of vitamin B9 is preferably 150 to 700 μg / day, more preferably 175 to 650 μg / day, and most preferably 200 to 600 μg / day. If present, the composition preferably contains 20 to 225 μg vitamin B9 / 100 ml, more preferably 25 to 200 μg vitamin B9 / 100 ml, and more preferably 30 to 175 μg vitamin B9 / 100 ml. Based on calories, preferably, the composition according to the invention may contain 16 to 80 μg vitamin B9 / 100 kcal, preferably 18 to 75 μg vitamin B9 / 100 kcal, more preferably 20 to 70 μg vitamin B9 / 100 kcal, based on the total energy content of the composition. The above figures are based on the molar weight of folic acid.

[0151] If present in the composition, vitamin B12 is preferably present in an amount providing a daily dose in the range of 2 to 20 μg per day, preferably in the range of 2.5 to 19 μg, more preferably in the range of 3 to 18 μg. When the composition is in the form of a tube feed, the daily administration of vitamin B9 is preferably 4 to 22 μg / day, more preferably 5 to 20 μg / day, and most preferably 6 to 18 μg / day. When the composition is in the form of an oral nutritional supplement, the daily administration of vitamin B9 is preferably 2 to 12 μg / day, more preferably 2.5 to 10 μg / day, and most preferably 3 to 9 μg / day. If present, the composition preferably contains 0.5 to 3 μg vitamin B12 / 100 ml, more preferably 0.6 to 2.6 μg vitamin B12 / 100 ml, and more preferably 0.7 to 2.4 μg vitamin B12 / 100 ml. Based on calories, preferably, the composition according to the invention may contain 0.4 to 1.4 μg vitamin B12 / 100 kcal, preferably 0.5 to 1.2 μg vitamin B12 / 100 kcal, more preferably 0.6 to 1 μg vitamin B12 / 100 kcal, based on the total energy content of the composition. The above figures are based on the molar weight of cyanocobalamin.

[0152] n-3PUFA

[0153] The composition of the present invention optionally further comprises ω-3 polyunsaturated fatty acids (PUFA), preferably n-3 LC-PUFA (long chain PUFA).

[0154] The composition comprises at least one, preferably two, ω-3 long-chain polyunsaturated fatty acids (LC-PUFA; having a chain length of 18 or more carbon atoms) selected from the group consisting of docosahexaenoic acid (22:6, ω-3; DHA), eicosapentaenoic acid (20:5, ω-3; EPA) and docosapentaenoic acid (22:5 ω-3; DPA), preferably DHA and EPA.

[0155] EPA is converted to DPA (ω-3), thereby increasing the subsequent conversion of DPA to DHA in the brain. The compositions of the present invention preferably contain a significant amount of EPA to further stimulate DHA formation in vivo.

[0156] DHA, EPA and / or DPA can be provided in any form, such as but not limited to triglycerides, diglycerides, monoglycerides, free fatty acids, or salts or esters thereof, phospholipids, lysophospholipids, glycerol ethers, lipoproteins, ceramides, glycolipids, or combinations thereof. Preferably, the composition of the present invention comprises at least DHA in the form of triglycerides.

[0157] Suitable sources of ω-3 LCPUFA and / or DHA and EPA include tuna oil, (other) fish oils, alkyl esters rich in DHA, algae oil, egg yolk, krill oil or phospholipids rich in ω-3 LCPUFA such as phosphatidylserine-DHA. Preferably, the composition or the composition for use according to the invention comprises fish oil providing one or more ω-3 LCPUFA. Another particularly suitable source of ω-3 LCPUFA is algae oil.

[0158] Preferably, DHA is administered in an amount of 100 to 1250 mg / day, more preferably 150 to 1200 mg / day, even more preferably 200 to 1100 mg / day, most preferably 250 to 1000 mg / day.

[0159] In an embodiment, when the composition is in the form of a tube feed, the daily administration amount of DHA is preferably 200 to 1100 mg / day, more preferably 250 to 1050 mg / day, most preferably 300 to 1000 mg / day.

[0160] In another embodiment, when the composition is in the form of an oral nutritional supplement, the daily administration amount of DHA is preferably 150 to 850 mg / day, more preferably 200 to 800 mg / day, and most preferably 250 to 750 mg / day.

[0161] The composition of the present invention preferably comprises 30 to 240 mg DHA / 100 ml of composition, preferably 35 to 220 mg DHA / 100 ml, more preferably 40 to 200 mg DHA / 100 ml of composition.

[0162] On a caloric basis, preferably the nutritional composition according to the invention comprises 20 to 100 mg DHA / 100 kcal, preferably 25 to 90 mg DHA / 100 kcal, more preferably 30 to 80 mg DHA / 100 kcal, based on the total energy content of the nutritional composition. The above figures are based on the molar weight of DHA.

[0163] Preferably, EPA is administered in an amount of 300 to 2400 mg / day, more preferably 400 to 2200 mg / day, most preferably 500 to 2000 mg / day.

[0164] In an embodiment, when the composition is in the form of a gavage, the daily administration amount of EPA is preferably 500 to 2300 mg / day, more preferably 600 to 2100 mg / day, and most preferably 650 to 2000 mg / day.

[0165] In another embodiment, when the composition is in the form of an oral nutritional supplement, the daily administration amount of EPA is preferably 300 to 1750 mg / day, more preferably 400 to 1600 mg / day, and most preferably 500 to 1500 mg / day.

[0166] The composition of the present invention preferably comprises 70 to 440 mg EPA / 100 ml composition, preferably 80 to 420 mg EPA / 100 ml, more preferably 90 to 400 mg EPA / 100 ml composition. Based on calories, preferably, the nutritional composition according to the present invention comprises 50 to 225 mg EPA / 100 kcal, preferably 60 to 200 mg EPA / 100 kcal, more preferably 70 to 170 mg EPA / 100 kcal, based on the total energy content of the nutritional composition. The above figures are based on the molar weight of EPA.

[0167] The weight ratio of DHA to EPA is preferably less than 1, more preferably 1: 1.1 to 1: 4, more preferably 1: 1.3 to 1: 2.5. In some embodiments, the weight ratio of DHA to EPA is about 1:2.

[0168] In terms of daily doses, the uses and methods of the present invention preferably comprise administering 400 to 3750 mg n-3 LC-PUFAs (preferably DHA+EPA+DPA, most preferably DHA+EPA) / day, more preferably 550 to 3500 mg / day, even more preferably 650 to 3250 mg / day, most preferably 750 to 3000 mg / day.

[0169] The composition of the present invention preferably comprises n-3 LC-PUFA (more preferably DHA+EPA+DPA, most preferably DHA+EPA), preferably 1 wt% to 8 wt%, more preferably 1.5 wt% to 7.5 wt%, most preferably 2 wt% to 7 wt%, based on total fatty acids.

[0170] The composition of the present invention preferably comprises 0.1wt% to 3.5wt% DHA based on total fatty acids, preferably 0.3wt% to 3wt% DHA based on total fatty acids, more preferably 0.5wt% to 2.5wt% DHA based on total fatty acids. The composition of the present invention preferably comprises 0.5wt% to 6wt% EPA based on total fatty acids, preferably 1wt% to 5wt% based on total fatty acids, most preferably 1.5wt% to 4.5wt% EPA.

[0171] The above ratios and amounts take into account and optimize several aspects including taste (too high n-3 LC-PUFA levels reduce taste, leading to reduced compliance), balance between DHA and its precursors to ensure optimal effectiveness while maintaining a low volume formulation.

[0172] choline

[0173] The composition of the present invention preferably optionally further comprises choline. Choline can exist as is, or exist as a choline equivalent in the form of a choline salt and / or a choline ester. Choline salts are preferably selected from choline chloride, choline bitartrate or choline stearate. Choline esters are preferably selected from phosphatidylcholine and lysophosphatidylcholine, preferably phosphatidylcholine. In a preferred embodiment, the composition of the present invention comprises a) choline or a choline salt as is and b) a choline ester, preferably phosphatidylcholine. This means that the composition of the present invention preferably comprises both: choline or a choline salt as is, and another choline ester, preferably phosphatidylcholine.

[0174] The compositions and methods of use of the present invention preferably comprise administration of more than 70 mg of a) choline or a choline salt per day, preferably 70 to 1300 mg / day, more preferably 80 to 1200 mg / day, most preferably 100 to 1100 mg / day.

[0175] In embodiments, when the composition is in the form of a gavage, the daily administration amount of choline or a choline salt is preferably 200 to 1400 mg / day, more preferably 300 to 1200 mg / day, most preferably 350 to 1100 mg / day.

[0176] In another embodiment, when the composition is in the form of an oral nutritional supplement, the daily administration amount of choline or choline salt is preferably 70 to 500 mg / day, more preferably 80 to 400 mg / day, and most preferably 100 to 300 mg / day.

[0177] The composition of the invention preferably comprises 30 to 180 mg a) choline or a choline salt per 100 ml liquid composition, preferably 35 to 170 mg choline per 100 ml, more preferably 40 to 160 mg choline per 100 ml composition, most preferably 45 to 150 mg choline per 100 ml.

[0178] On a caloric basis, preferably the nutritional composition according to the invention comprises 25 to 110 mg choline / 100 kcal, preferably 30 to 105 mg choline / 100 kcal, more preferably 33 to 100 mg / 100 kcal, based on the total energy content of the nutritional composition.

[0179] The above figures are based on choline, and the amount of choline salt or ester can be calculated taking into account the molar equivalent of choline.

[0180] Compositions of the present invention may include choline in the form of choline esters, preferably provided in the form of phospholipids. Preferably, one or more phospholipids are present in compositions according to the present invention. The one or more phospholipids are selected from the group consisting of: phosphatidic acid (PA), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS) and phosphoinositide (PI), preferably at least phosphatidylcholine. In a preferred embodiment, phospholipids are the source of choline ester phosphatidylcholine.

[0181] Suitable sources of phospholipids herein are soy lecithin, egg lecithin, and rapeseed and sunflower lecithin. Milk contains phospholipids in the milk fat globule membrane (MFGM), and suitable sources include milk phospholipid concentrates such as those commercially available from Lecico Ltd, whey protein concentrate from Arla Foods |MFGM. Depending on the source, the phospholipids contain about 10 wt% to 40 wt% phosphatidylcholine.

[0182] If present, the composition and the use or method of using the composition preferably comprises administering a phospholipid in an amount of 0.6 to 6.6 g mg / day, preferably 0.8 to 6.4 g phospholipid / day, more preferably 0.9 to 6.2 g phospholipid / day, most preferably 1 to 6 g phospholipid / day. In one aspect, the amount of the phospholipid is about 200 mg / day. The phospholipid preferably provides at least phosphatidylcholine.

[0183] If present, the composition of the invention preferably comprises phospholipids in an amount between 150 and 900 mg / 100 ml, more preferably between 200 and 850 mg / 100 ml, most preferably between 250 and 800 mg / 100 ml. The phospholipids preferably provide at least phosphatidylcholine.

[0184] In an embodiment, when the composition is in the form of a gavage, the daily administration amount of the phospholipid is preferably 1 to 7 g / day, more preferably 1.5 to 6.5 g / day, most preferably 2 to 6 g / day.

[0185] In another embodiment, when the composition is in the form of an oral nutritional supplement, the daily administration amount of the phospholipid is preferably 0.5 to 4 g / day, more preferably 0.75 to 3.5 g / day, and most preferably 1 to 3 g / day.

[0186] On a caloric basis, preferably the nutritional composition according to the invention comprises 100 to 500 mg phospholipids / 100 kcal, preferably 150 to 400 mg phospholipids / 100 kcal, more preferably 200 to 350 mg phospholipids / 100 kcal, based on the total energy content of the nutritional composition.

[0187] In a specific embodiment, the nutritional composition according to the present invention comprises a) choline or a choline salt and b) phosphatidylcholine (PC). In such an embodiment, the weight ratio of phosphatidylcholine to choline is generally greater than 0.1, preferably greater than 0.26, particularly 0.30-6, more preferably 0.36-3. In a further preferred embodiment, the ratio of phosphatidylcholine to choline is in the range of 40:60 to 60:40. In this article, the amount of choline expressed in grams will be calculated as the molar contribution of choline provided by all choline sources (including PC when orally digested and assuming 100% bioavailability) multiplied by the molecular weight of choline (104g / mol). Herein, the molecular weight of PC is 810g / mol. Thus, for example, including 400 mg choline chloride (molecular weight 139.6 g / mol) and 200 mg phosphatidylcholine and 200 mg PL other than PC would result in a weight ratio of PC to choline of 200 / [(104 / 139.6)x400+(104 / 810)x200]=200 / [298+25.7]=0.62.

[0188] The presence of PC is particularly preferred because the content of choline (salt) can be reduced while still providing a bioavailable source of choline. In addition, dietary choline can be metabolized to trimethylamine (TMA) in the intestine, which in turn is oxidized to trimethylamine N-oxide (TMAO) in the liver. Both TMA and TMAO are associated with an increased risk of cardiovascular disease (Zhu et al., Cell 2016; Jaworska et al. Cardiovac. Res 2019), so it is preferred to provide choline in free (salt) form and as phosphatidylcholine.

[0189] Preferably, the composition according to the invention comprising a combination of (i) coenzyme Q10 with (ii) vitamin D and (iii) vitamin B2 (optionally in combination with one or more of vitamins B6 and B9) and optionally (iv) polyunsaturated fatty acids and / or (v) choline further comprises one or more selected from vitamin A, additional vitamins B, C and E, phospholipids, selenium and magnesium. More preferably, the composition contains two or more of these additional ingredients. Additional ingredients and their corresponding amounts will be discussed later.

[0190] Vitamin A

[0191] The composition of the present invention may further comprise vitamin A. Vitamin A is a fat-soluble vitamin that appears in several forms (e.g., retinol, retinal, retinoic acid, or retinyl esters). Any functional form of vitamin A known in the art is suitable for use herein, including retinol (particularly retinol esters), retinal, retinoic acid, beta-carotene, provitamin A, or any combination thereof. Preferably, the composition comprises retinol, particularly retinyl acetate and / or retinyl palmitate.

[0192] Vitamin A intake or requirements are usually expressed in the form of retinol equivalents (RE). One RE is defined as the biological activity associated with 1 μg of all-trans retinol. Thus, 1 μg of retinol equivalent is similar to 1 μg of all-trans retinol. One international unit (IU) of retinol is equivalent to 0.3 μg of retinol equivalent.

[0193] If present in the composition, vitamin A is preferably administered in an amount of 300 to 2800 μg retinol equivalents / day, more preferably 350 to 2700 μg retinol equivalents / day, even more preferably 650 to 900 μg retinol equivalents / day, most preferably 375 to 2600 μg retinol equivalents / day.

[0194] In an embodiment, the composition is in the form of a tube feed, and the daily administration amount of vitamin A is preferably 700 to 2850 μg retinol equivalent / day, more preferably 800 to 2750 μg retinol equivalent / day, most preferably 850 to 2600 μg retinol equivalent / day.

[0195] In another embodiment, the composition is in the form of an oral nutritional supplement, and the daily administration amount of vitamin A is preferably 300 to 1200 μg retinol equivalents / day, more preferably 350 to 1150 μg retinol equivalents / day, most preferably 375 to 1125 μg retinol equivalents / day.

[0196] The composition of the present invention may preferably contain vitamin A, preferably 50 to 400 μg retinol equivalent / 100 ml composition, more preferably 75 to 350 μg retinol equivalent / 100 ml, most preferably 100 to 300 μg retinol equivalent / 100 ml composition.

[0197] Based on calories, preferably, the nutritional composition according to the present invention may contain 60 to 150 μg retinol equivalent / 100 kcal, preferably 70 to 140 μg retinol equivalent / 100 kcal, more preferably 80 to 130 μg retinol equivalent / 100 kcal, based on the total energy content of the nutritional composition.

[0198] Vitamin C

[0199] The composition of the present invention may further include vitamin C. Vitamin C is an antioxidant that can provide beneficial features during and after hypoxia (such as stroke). Vitamin C includes its functional equivalents (including sodium ascorbate and calcium ascorbate), and can be present in an amount providing a daily dose in the range of 75 to 700 mg, preferably in the range of 85 to 600 mg, more preferably in the range of 95 to 550 mg. When the composition is a tube feeding form, the daily application amount of vitamin C is preferably 140 to 600 mg / days, more preferably 160 to 575 mg / days, and most preferably 180 to 550 mg / days. When the composition is an oral nutritional supplement form, the daily application amount of vitamin C is preferably 80 to 320 mg / days, more preferably 90 to 300 mg / days, and most preferably 95 to 290 mg / days. In one embodiment, if present, vitamin C is present in the range of 10 to 100 mg per 100 ml composition, preferably in the range of 15 to 90 mg, and more preferably in the range of 20 to 80 mg. Based on calories, preferably, the composition according to the invention may contain 12 to 40 mg vitamin C / 100 kcal, preferably 14 to 35 mg vitamin C / 100 kcal, more preferably 16 to 32 mg vitamin C / 100 kcal, based on the total energy content of the composition. The above figures are based on the molar weight of ascorbic acid.

[0200] Vitamin E

[0201] The composition according to the invention may comprise vitamin E. Vitamin E refers to a compound having vitamin E activity as known in the art, typically tocopherol and / or its equivalent.

[0202] If included, vitamin E can be present in the composition in an amount that provides a daily dose of α-TE in the range of 8 to 75 mg, preferably in the range of 10 to 70 mg, and more preferably in the range of 12.5 to 70 mg. When the composition is in the form of a tube feed, the daily application of vitamin E is preferably 18 to 80 mg / day, more preferably 20 to 75 mg / day, and most preferably 22 to 70 mg α-TE / day. When the composition is in the form of an oral nutritional supplement, the daily application of vitamin E is preferably 8 to 42 mg / day, more preferably 10 to 40 mg / day, and most preferably 12.5 to 37.5 mg α-TE / day. Such an amount of vitamin E prevents oxidative damage to the site of injury. In one embodiment, tocopherol and / or an equivalent are present in an amount in the range of 2 to 14 mg α-TE per 100 ml composition, preferably in the range of 2.5 to 12 mg α-TE, and more preferably in the range of 2.75 to 10 mg α-TE. Based on calories, preferably, the composition according to the present invention may contain 1 to 5.5 mg α-TE / 100 kcal, preferably 1.5 to 5 mg α-TE / 100 kcal, more preferably 2 to 4.5 mg α-TE / 100 kcal, based on the total energy content of the composition.

[0203] As used in this specification, the term "tocopherol and / or its equivalent" includes tocopherols (e.g., α-tocopherol and γ-tocopherol), tocotrienols, pharmaceutically and / or nutritionally acceptable derivatives thereof, and any combination thereof. The above figures are based on α-tocopherol equivalents (α-TE) and their molecular weights, as recognized in the art.

[0204] Vitamin K1

[0205] The composition according to the invention may optionally contain vitamin K, preferably vitamin K1, although it is preferred that the composition contains no or minimal amounts of vitamin K. Vitamin K is the common name for a group of compounds containing a 2-methyl-1,4-naphthoquinone nucleus and having side chains of different lipophilicity at position 3, hereinafter also referred to as "K vitamins". Vitamin K exists naturally in the form of vitamin K1 (phytomenaquinone, phytonaphthoquinone, α-phylloquinone) and vitamin K2 (toluoquinone), which is produced by gastrointestinal bacteria in essentially two different isoforms, namely vitamin K2 (35) (C46H64O2) and vitamin K2 (30) (C41H56O2). Vitamin K3 (menaquinone) is a provitamin that can be converted into vitamin K2 by animals.

[0206] If present in the composition, vitamin K1 is preferably present in a daily dose of at most 240 μg, preferably at most 200 μg, more preferably at most 100 μg / day. The composition of the present invention preferably contains less than 40 μg vitamin K1 / 100 ml, more preferably less than 35 μg vitamin K1 / 100 ml, more preferably less than 30 μg vitamin K1 / 100 ml. Based on calories, preferably, the composition according to the present invention may contain less than 18 μg vitamin K1 / 100 kcal, preferably less than 16 μg vitamin K1 / 100 kcal, more preferably less than 15 μg vitamin K1 / 100 kcal based on the total energy content of the composition. The above figures are based on the molar weight of phylloquinone.

[0207] In a preferred embodiment, the composition comprises less than 15 μg vitamin K1 / 100 kcal.

[0208] selenium

[0209] The composition of the present invention may include selenium. The antioxidant activity of selenium may advantageously prevent and / or inhibit damage to brain regions.

[0210] If present in the composition, selenium is preferably present in an amount providing a daily dose in the range of 30 to 275 μg per day, preferably in the range of 35 to 250 μg, more preferably in the range of 38 to 225 μg. When the composition is in the form of a tube feed, the daily application amount of selenium is preferably 60 to 275 μg / day, more preferably 70 to 250 μg / day, and most preferably 75 to 225 μg / day. When the composition is in the form of an oral nutritional supplement, the daily application amount of selenium is preferably 25 to 140 μg / day, more preferably 30 to 130 μg / day, and most preferably 35 to 120 μg / day. The composition of the present invention preferably comprises 8 to 45 μg selenium / 100 ml, more preferably 10 to 40 μg selenium / 100 ml, and more preferably 11 to 35 μg selenium / 100 ml. On a caloric basis, preferably, the composition according to the invention may comprise 4 to 18 μg selenium / 100 kcal, preferably 6 to 16 μg selenium / 100 kcal, more preferably 8 to 14 μg selenium / 100 kcal, based on the total energy content of the composition.

[0211] magnesium

[0212] The composition of the present invention may contain magnesium. Magnesium plays a vital role in neurotransmission and neuromuscular conduction. It also plays a protective role against excessive excitation that may lead to neuronal cell death (excitotoxicity).

[0213] If present in the composition, magnesium is preferably present in an amount providing a daily dose in the range of 125 to 850 mg, preferably in the range of 150 to 800 mg, more preferably in the range of 170 to 750 mg. When the composition is in the form of a tube feed, the daily dosage of magnesium is preferably 200 to 780 mg / day, more preferably 220 to 760 mg / day, and most preferably 240 to 740 mg / day. When the composition is in the form of an oral nutritional supplement, the daily dosage of magnesium is preferably 150 to 600 mg / day, more preferably 160 to 550 mg / day, and most preferably 170 to 525 mg / day. The composition of the present invention preferably comprises 20 to 160 mg magnesium / 100 ml, more preferably 25 to 150 mg magnesium / 100 ml, and more preferably 30 to 140 mg magnesium / 100 ml. On a caloric basis, preferably, the composition according to the invention may comprise 10 to 70 mg magnesium / 100 kcal, preferably 15 to 65 mg magnesium / 100 kcal, more preferably 20 to 60 mg magnesium / 100 kcal, based on the total energy content of the composition.

[0214] The composition may contain additional minerals including, but not limited to, sodium, potassium, chloride, calcium, phosphorus, iron, zinc, copper, manganese, fluorite, molybdenum, chromium and iodine in amounts consistent with the general recommendations for the nutritional requirements of the FSMP.

[0215] LA / ALA

[0216] In addition to LC-PUFA, the lipid fraction further comprises lipids that are a source of the essential fatty acids alpha-linolenic acid (ALA, C-18:3) and linoleic acid (LA, C-18:2). LA and / or ALA may be provided as free fatty acids, triglyceride form, diglyceride form, monoglyceride form, phospholipid form or a mixture of one or more of the above. Preferably, the composition of the present invention contains at least one, preferably at least two lipid sources selected from the group consisting of: soybean oil, rapeseed oil (such as colza oil, canola oil and canola oil), high oleic sunflower oil, high oleic safflower oil and olive oil. The LA:ALA weight ratio is preferably in the range of 8:1 to 3:1, preferably 7:1 to 4:1, more preferably 6:1 to 5:1.

[0217] If present in the composition, the composition of the invention preferably comprises 0.2 to 3.5 g LA / 100 ml, more preferably 0.3 to 3 g LA / 100 ml, more preferably 0.4 to 2.5 g LA / 100 ml. On a caloric basis, preferably, the composition according to the invention may comprise 0.1 to 1.5 g LA / 100 kcal, preferably 0.2 to 1.1 g LA / 100 kcal, more preferably 0.25 to 1 g LA / 100 kcal, based on the total energy content of the composition.

[0218] If present in the composition, the composition of the present invention preferably comprises 0.02 to 0.2 g ALA / 100 ml, more preferably 0.05 to 0.15 g ALA / 100 ml, more preferably 0.06 to 0.1 g ALA / 100 ml. On a caloric basis, preferably, the composition according to the present invention may comprise 0.03 to 0.08 g ALA / 100 kcal, preferably 0.04 to 0.07 g ALA / 100 kcal, more preferably 0.05 to 0.065 g ALA / 100 kcal based on the total energy content of the composition.

[0219] In particularly preferred embodiments, compositions suitable for use in subjects suffering from stroke, preferably ischemic stroke, are provided.

[0220] This nutritional composition according to the present invention suitably comprises (i) coenzyme Q10 in combination with (ii) vitamin D and (iii) vitamin B2, optionally further comprising (iv) polyunsaturated fatty acids and / or (v) choline. In an embodiment, the composition comprises a combination of coenzyme Q10, vitamin D and vitamin B2 in combination with one or more of vitamins B6 and B9. Preferably, the composition according to the present invention further comprises one or more selected from vitamin A, additional vitamins B, C and E, phospholipids, selenium and magnesium.

[0221] Preferably, the composition according to the present invention further comprises one or more selected from vitamins A, B, C and E, phospholipids, selenium and magnesium. Preferably, the composition according to the present invention further comprises one or more of vitamins B1, B6, B9 and vitamin B12. In another preferred embodiment, the composition comprises vitamin D3, coenzyme Q10, vitamin B2, polyunsaturated fatty acids, choline, and one or more of vitamins B1, B6, B9, B12, vitamin A, vitamin C, vitamin E, selenium, magnesium and phospholipids, preferably all.

[0222] In an embodiment, the composition according to the invention comprises per daily dose:

[0223] (i) 8 to 80 mg, preferably 10 to 70 mg, more preferably 15 to 60 mg coenzyme Q10; and

[0224] (ii) 6 to 75 μg, preferably 8 to 70 μg, more preferably 10 to 65 μg vitamin D, preferably vitamin D3;

[0225] as well as

[0226] (iii) 0.8 to 7.6 mg, preferably 1 to 7.4 mg, more preferably 1.2 to 7.2 mg of vitamin B2; and optionally

[0227] (iv) 150 to 1200 mg, preferably 200 to 1100 mg, more preferably 250 to 1000 mg DHA; and / or

[0228] 300 to 2400 mg, preferably 400 to 2200 mg, more preferably 500 to 2000 mg / day of EPA; and / or

[0229] (v) 200-1400 mg, preferably 300-1200 mg, more preferably 350-1100 mg choline or a choline salt.

[0230] In an embodiment, the composition according to the invention comprises per daily dose:

[0231] (i) 8 to 80 mg, preferably 10 to 70 mg, more preferably 15 to 60 mg coenzyme Q10; and

[0232] (ii) 6 to 75 μg, preferably 8 to 70 μg, more preferably 10 to 65 μg vitamin D, preferably vitamin D3;

[0233] as well as

[0234] (iii) vitamin B2 in the range of 0.8 to 7.6 mg, preferably 1 to 7.4 mg, more preferably 1.2 to 7.2 mg;

[0235] (iv) 150 to 1200 mg, preferably 200 to 1100 mg, more preferably 250 to 1000 mg DHA; and / or

[0236] 300 to 2400 mg, preferably 400 to 2200 mg, more preferably 500 to 2000 mg / day of EPA; and

[0237] (v) 200 to 1400 mg, preferably 300 to 1200 mg, more preferably 350 to 1100 mg of choline, based on the molar weight of choline, wherein the choline is selected from free choline, choline salts and / or choline esters, preferably at least phosphatidylcholine.

[0238] In an embodiment, the composition according to the invention comprises per daily dose:

[0239] (i) 8 to 80 mg, preferably 10 to 70 mg, more preferably 15 to 60 mg coenzyme Q10;

[0240] (ii) 6 to 75 μg, preferably 8 to 70 μg, more preferably 10 to 65 μg vitamin D, preferably vitamin D3; and optionally

[0241] (iv) 150 to 1200 mg, preferably 200 to 1100 mg, more preferably 250 to 1000 mg DHA; and / or

[0242] 300 to 2400 mg, preferably 400 to 2200 mg, more preferably 500 to 2000 mg / day of EPA;

[0243] (v) 200-1400 mg, preferably 300-1200 mg, more preferably 350-1100 mg choline or a choline salt.

[0244] In a further embodiment, the composition according to the present invention comprises per daily dose:

[0245] (i) 8 to 80 mg, preferably 10 to 70 mg, more preferably 15 to 60 mg coenzyme Q10;

[0246] (ii) 6 to 75 μg, preferably 8 to 70 μg, more preferably 10 to 65 μg vitamin D, preferably vitamin D3;

[0247] (iii) 0.8 to 7.6 mg, preferably 1 to 7.4 mg, more preferably 1.2 to 7.2 mg vitamin B2;

[0248] A combination with at least one of (vi) and (vii)

[0249] (vi) 0.7 to 9 mg, preferably 0.8 to 8 mg, more preferably 0.9 to 7.5 mg vitamin B6;

[0250] (vii) 150 to 900 μg, preferably 175 to 800 μg, more preferably 200 to 750 μg vitamin B9

[0251] and optionally

[0252] (iv) 150 to 1200 mg, preferably 200 to 1100 mg, more preferably 250 to 1000 mg DHA; and / or

[0253] 300 to 2400 mg, preferably 400 to 2200 mg, more preferably 500 to 2000 mg / day of EPA;

[0254] (v) 200-1400 mg, preferably 300-1200 mg, more preferably 350-1100 mg choline or a choline salt.

[0255] In a further embodiment, the composition according to the present invention comprises per daily dose:

[0256] (i) 8 to 80 mg, preferably 10 to 70 mg, more preferably 15 to 60 mg coenzyme Q10;

[0257] (ii) 6 to 75 μg, preferably 8 to 70 μg, more preferably 10 to 65 μg vitamin D, preferably vitamin D3;

[0258] (iii) 0.8 to 7.6 mg, preferably 1 to 7.4 mg, more preferably 1.2 to 7.2 mg vitamin B2;

[0259] In combination with:

[0260] (iv) 150 to 1200 mg, preferably 200 to 1100 mg, more preferably 250 to 1000 mg DHA; and / or

[0261] 300 to 2400 mg, preferably 400 to 2200 mg, more preferably 500 to 2000 mg / day of EPA;

[0262] (v) 200 to 1400 mg, preferably 300 to 1200 mg, more preferably 350 to 1100 mg choline, wherein the choline is selected from free choline, choline salts and / or choline esters, preferably at least phosphatidylcholine.

[0263] In a further embodiment, the composition according to the present invention comprises per daily dose:

[0264] (i) 8 to 80 mg, preferably 10 to 70 mg, more preferably 15 to 60 mg coenzyme Q10;

[0265] (ii) 6 to 75 μg, preferably 8 to 70 μg, more preferably 10 to 65 μg vitamin D, preferably vitamin D3;

[0266] (iii) 0.8 to 7.6 mg, preferably 1 to 7.4 mg, more preferably 1.2 to 7.2 mg vitamin B2;

[0267] In combination with:

[0268] (iv) 150 to 1200 mg, preferably 200 to 1100 mg, more preferably 250 to 1000 mg DHA; and / or

[0269] 300 to 2400 mg, preferably 400 to 2200 mg, more preferably 500 to 2000 mg / day of EPA;

[0270] (v) 200 to 1400 mg, preferably 300 to 1200 mg, more preferably 350 to 1100 mg choline, wherein the choline is selected from free choline, choline salts and / or choline esters, preferably at least phosphatidylcholine.

[0271] In a further embodiment, the composition according to the present invention comprises per daily dose:

[0272] (i) 8 to 80 mg, preferably 10 to 70 mg, more preferably 15 to 60 mg coenzyme Q10;

[0273] (ii) 6 to 75 μg, preferably 8 to 70 μg, more preferably 10 to 65 μg vitamin D, preferably vitamin D3;

[0274] (iii) 0.8 to 7.6 mg, preferably 1 to 7.4 mg, more preferably 1.2 to 7.2 mg vitamin B2;

[0275] In combination with:

[0276] (iv) 150 to 1200 mg, preferably 200 to 1100 mg, more preferably 250 to 1000 mg DHA; and / or

[0277] 300 to 2400 mg, preferably 400 to 2200 mg, more preferably 500 to 2000 mg / day of EPA;

[0278] (v) 200 to 1400 mg, preferably 300 to 1200 mg, more preferably 350 to 1100 mg choline, wherein the choline is selected from free choline, choline salts and / or choline esters, wherein the composition preferably comprises v a ) phosphatidylcholine and v b ) choline or a salt thereof, and wherein the weight ratio of phosphatidylcholine to choline is greater than 0.1.

[0279] In a further embodiment, the composition according to the present invention comprises per daily dose:

[0280] (i) 8 to 80 mg, preferably 10 to 70 mg, more preferably 15 to 60 mg coenzyme Q10;

[0281] (ii) 6 to 75 μg, preferably 8 to 70 μg, more preferably 10 to 65 μg vitamin D, preferably vitamin D3;

[0282] (iii) 0.8 to 7.6 mg, preferably 1 to 7.4 mg, more preferably 1.2 to 7.2 mg vitamin B2;

[0283] In combination with:

[0284] (iv) 150 to 1200 mg, preferably 200 to 1100 mg, more preferably 250 to 1000 mg DHA; and / or

[0285] 300 to 2400 mg, preferably 400 to 2200 mg, more preferably 500 to 2000 mg / day of EPA;

[0286] (v) 200 to 1400 mg, preferably 300 to 1200 mg, more preferably 350 to 1100 mg choline, wherein the choline is selected from free choline, choline salts and / or choline esters, preferably at least phosphatidylcholine.

[0287] In a further embodiment, the composition according to the present invention comprises per daily dose:

[0288] (i) 8 to 80 mg, preferably 10 to 70 mg, more preferably 15 to 60 mg coenzyme Q10;

[0289] (ii) 6 to 75 μg, preferably 8 to 70 μg, more preferably 10 to 65 μg vitamin D, preferably vitamin D3;

[0290] (iii) 0.8 to 7.6 mg, preferably 1 to 7.4 mg, more preferably 1.2 to 7.2 mg vitamin B2;

[0291] In combination with:

[0292] (iv) 150 to 1200 mg, preferably 200 to 1100 mg, more preferably 250 to 1000 mg DHA; and / or

[0293] 300 to 2400 mg, preferably 400 to 2200 mg, more preferably 500 to 2000 mg / day of EPA;

[0294] (v) 200 to 1400 mg, preferably 300 to 1200 mg, more preferably 350 to 1100 mg choline, wherein the choline is selected from free choline, choline salts and / or choline esters, wherein the composition preferably comprises v a ) phosphatidylcholine and v b ) choline or a salt thereof, and wherein the weight ratio of phosphatidylcholine to choline is greater than 0.1.

[0295] In a further preferred embodiment, the composition comprising at least one of (i), (ii) and (iii), (vi) and (vii) and optionally a combination of (iv) and / or (v) per daily dose further comprises one or more of the following:

[0296] (viii) 350 to 2700 μg retinol equivalents, preferably 650 to 900 μg retinol equivalents, more preferably 375 to 2600 μg retinol equivalents of vitamin A;

[0297] (ix) 0.7 to 5 mg, preferably 0.8 to 4.9 mg, more preferably 0.9 to 4.8 mg vitamin B1;

[0298] (x) 2 to 20 μg, preferably 2.5 to 19 μg, more preferably 3 to 18 μg vitamin B12;

[0299] (xi) 75 to 700 mg, preferably 85 to 600 mg, more preferably 95 to 550 mg vitamin C;

[0300] (xii) 8 to 75 mg, preferably 10 to 70 mg, more preferably 12.5 to 70 mg α-TE;

[0301] (xiii) 30 to 275 μg, preferably 35 to 250 μg, more preferably 38 to 225 μg selenium; and

[0302] (xiv) 125 to 850 mg, preferably 150 to 800 mg, more preferably 170 to 750 mg magnesium.

[0303] In another preferred embodiment, the composition comprises at least one of (i), (ii), (iii), (iv) and (v), (vi) and (vii) per daily dose, and one or more of the following:

[0304] (viii) 350 to 2700 μg retinol equivalents, preferably 650 to 900 μg retinol equivalents, more preferably 375 to 2600 μg retinol equivalents of vitamin A;

[0305] (ix) 0.7 to 5 mg, preferably 0.8 to 4.9 mg, more preferably 0.9 to 4.8 mg vitamin B1;

[0306] (x) 2 to 20 μg, preferably 2.5 to 19 μg, more preferably 3 to 18 μg vitamin B12;

[0307] (xi) 75 to 700 mg, preferably 85 to 600 mg, more preferably 95 to 550 mg vitamin C;

[0308] (xii) 8 to 75 mg, preferably 10 to 70 mg, more preferably 12.5 to 70 mg α-TE;

[0309] (xiii) 30 to 275 μg, preferably 35 to 250 μg, more preferably 38 to 225 μg selenium; and

[0310] (xiv) 125 to 850 mg, preferably 150 to 800 mg, more preferably 170 to 750 mg magnesium.

[0311] In another preferred embodiment, the composition comprises (i), (ii) and (iii), at least one of (vi) and (vii) and optionally (iv) and / or (v), a combination of one or more selected from (vii)-(xiv), per daily dose, further comprising at least one of the following:

[0312] (xv) 3 to 45 mg, preferably 3.5 to 42 mg, more preferably 3.8 to 40 mg vitamin B3 (niacin equivalent);

[0313] (xvi) 0.8 to 15 mg, preferably 1 to 14 mg, more preferably 1.2 to 13 mg vitamin B5;

[0314] (xvii) Vitamin B7 in the range of 8 to 95 μg, preferably in the range of 9 to 90 μg, more preferably in the range of 9.5 to 85 μg.

[0315] The present invention also provides a liquid nutritional composition, wherein each 100 ml of the liquid nutritional composition comprises:

[0316] (i) 1 to 15 mg, preferably 1.5 to 14 mg, more preferably 2 to 13 mg coenzyme Q10; and

[0317] (ii) 1.5 to 10 μg, preferably 2 to 9 μg, more preferably 2.5 to 8 μg vitamin D, preferably vitamin D3; and

[0318] (iii) 0.1 to 1.4 mg, preferably 0.2 to 1.2 mg, more preferably 0.3 to 1 mg vitamin B2; and optionally

[0319] (iv) 30 to 240 mg, preferably 35 to 220 mg, more preferably 40 to 200 mg DHA; and / or

[0320] 70 to 440 mg, preferably 80 to 420 mg, more preferably 90 to 400 mg EPA; and / or,

[0321] (v) 35 to 170 mg, preferably 40 to 160 mg, more preferably 45 to 150 mg choline or a choline salt.

[0322] The present invention also provides a liquid nutritional composition, wherein each 100 ml of the liquid nutritional composition comprises:

[0323] (i) 1 to 15 mg, preferably 1.5 to 14 mg, more preferably 2 to 13 mg coenzyme Q10; and

[0324] (ii) 1.5 to 10 μg, preferably 2 to 9 μg, more preferably 2.5 to 8 μg vitamin D, preferably vitamin D3; and

[0325] (iii) 0.1 to 1.4 mg, preferably 0.2 to 1.2 mg, more preferably 0.3 to 1 mg vitamin B2; and optionally

[0326] (iv) 30 to 240 mg, preferably 35 to 220 mg, more preferably 40 to 200 mg DHA; and / or

[0327] 70 to 440 mg, preferably 80 to 420 mg, more preferably 90 to 400 mg EPA; and / or,

[0328] (v) 35 to 170 mg, preferably 40 to 160 mg, more preferably 45 to 150 mg choline, wherein the choline is selected from free choline, choline salts and / or choline esters, preferably at least phosphatidylcholine.

[0329] The present invention also provides a liquid nutritional composition, wherein each 100 ml of the liquid nutritional composition comprises:

[0330] (i) 1 to 15 mg, preferably 1.5 to 14 mg, more preferably 2 to 13 mg coenzyme Q10;

[0331] (ii) 1.5 to 10 μg, preferably 2 to 9 μg, more preferably 2.5 to 8 μg vitamin D, preferably vitamin D3;

[0332] (iii) 0.1 to 1.4 mg, preferably 0.2 to 1.2 mg, more preferably 0.3 to 1 mg vitamin B2;

[0333] (iv) 30 to 240 mg, preferably 35 to 220 mg, more preferably 40 to 200 mg DHA; and / or

[0334] 70 to 440 mg, preferably 80 to 420 mg, more preferably 90 to 400 mg EPA;

[0335] as well as

[0336] (v) 35 to 170 mg, preferably 40 to 160 mg, more preferably 45 to 150 mg choline.

[0337] The present invention also provides a liquid nutritional composition, wherein each 100 ml of the liquid nutritional composition comprises:

[0338] (i) 1 to 15 mg, preferably 1.5 to 14 mg, more preferably 2 to 13 mg coenzyme Q10;

[0339] (ii) 1.5 to 10 μg, preferably 2 to 9 μg, more preferably 2.5 to 8 μg vitamin D, preferably vitamin D3;

[0340] (iii) 0.1 to 1.4 mg, preferably 0.2 to 1.2 mg, more preferably 0.3 to 1 mg vitamin B2;

[0341] (iv) 30 to 240 mg, preferably 35 to 220 mg, more preferably 40 to 200 mg DHA; and / or

[0342] 70 to 440 mg, preferably 80 to 420 mg, more preferably 90 to 400 mg EPA;

[0343] (v) 35 to 170 mg, preferably 40 to 160 mg, more preferably 45 to 150 mg choline, wherein the choline is selected from free choline, choline salts and / or choline esters, preferably at least phosphatidylcholine.

[0344] The present invention further provides a liquid nutritional composition, wherein each 100 ml of the liquid nutritional composition comprises:

[0345] (i) 1 to 15 mg, preferably 1.5 to 14 mg, more preferably 2 to 13 mg coenzyme Q10; and

[0346] (ii) 1.5 to 10 μg, preferably 2 to 9 μg, more preferably 2.5 to 8 μg vitamin D, preferably vitamin D3; and

[0347] (iii) 0.1 to 1.4 mg, preferably 0.2 to 1.2 mg, more preferably 0.3 to 1 mg vitamin B2; and optionally

[0348] (iv) 30 to 240 mg, preferably 35 to 220 mg, more preferably 40 to 200 mg DHA; and / or

[0349] 70 to 440 mg, preferably 80 to 420 mg, more preferably 90 to 400 mg EPA; and / or,

[0350] (v) 35 to 170 mg, preferably 40 to 160 mg, more preferably 45 to 150 mg choline, wherein the choline is selected from free choline, choline salts and / or choline esters, preferably at least phosphatidylcholine, wherein the composition preferably comprises v a ) phosphatidylcholine and v b ) choline or a salt thereof, and wherein the weight ratio of phosphatidylcholine to choline is greater than 0.1.

[0351] In another embodiment, a liquid nutritional composition is provided, wherein each 100 ml of the liquid nutritional composition comprises:

[0352] (i) 1 to 15 mg, preferably 1.5 to 14 mg, more preferably 2 to 13 mg coenzyme Q10; and

[0353] (ii) 1.5 to 10 μg, preferably 2 to 9 μg, more preferably 2.5 to 8 μg vitamin D, preferably vitamin D3;

[0354] and optionally

[0355] (iv) 30 to 240 mg, preferably 35 to 220 mg, more preferably 40 to 200 mg DHA; and / or

[0356] 70 to 440 mg, preferably 80 to 420 mg, more preferably 90 to 400 mg EPA; and / or,

[0357] (v) 35 to 170 mg, preferably 40 to 160 mg, more preferably 45 to 150 mg choline or a choline salt.

[0358] In another embodiment, a liquid nutritional composition is provided, wherein each 100 ml of the liquid nutritional composition comprises:

[0359] i) 1 to 15 mg, preferably 1.5 to 14 mg, more preferably 2 to 13 mg coenzyme Q10; and

[0360] (ii) 1.5 to 10 μg, preferably 2 to 9 μg, more preferably 2.5 to 8 μg vitamin D, preferably vitamin D3;

[0361] (iii) 0.1 to 1.4 mg, preferably 0.2 to 1.2 mg, more preferably 0.3 to 1 mg vitamin B2;

[0362] and at least one of (vi) and (vii);

[0363] (vi) 0.2 to 1 mg, preferably 0.25 to 0.8 mg, more preferably 0.3 to 0.7 mg vitamin B6;

[0364] (vii) 20 to 225 μg, preferably 25 to 200 μg, more preferably 30 to 175 μg vitamin B9;

[0365] and optionally

[0366] (iv) 30 to 240 mg, preferably 35 to 220 mg, more preferably 40 to 200 mg DHA; and / or

[0367] 70 to 440 mg, preferably 80 to 420 mg, more preferably 90 to 400 mg EPA; and / or,

[0368] (v) 35 to 170 mg, preferably 40 to 160 mg, more preferably 45 to 150 mg choline or a choline salt.

[0369] In another embodiment, a liquid nutritional composition is provided, wherein each 100 ml of the liquid nutritional composition comprises:

[0370] i) 1 to 15 mg, preferably 1.5 to 14 mg, more preferably 2 to 13 mg coenzyme Q10;

[0371] (ii) 1.5 to 10 μg, preferably 2 to 9 μg, more preferably 2.5 to 8 μg vitamin D, preferably vitamin D3;

[0372] (iii) 0.1 to 1.4 mg, preferably 0.2 to 1.2 mg, more preferably 0.3 to 1 mg vitamin B2;

[0373] (iv) 30 to 240 mg, preferably 35 to 220 mg, more preferably 40 to 200 mg DHA; and / or

[0374] 70 to 440 mg, preferably 80 to 420 mg, more preferably 90 to 400 mg EPA;

[0375] (v) 35 to 170 mg, preferably 40 to 160 mg, more preferably 45 to 150 mg choline, and

[0376] At least one of (vi) and (vii);

[0377] (vi) 0.2 to 1 mg, preferably 0.25 to 0.8 mg, more preferably 0.3 to 0.7 mg vitamin B6;

[0378] (vii) 20 to 225 μg, preferably 25 to 200 μg, more preferably 30 to 175 μg vitamin B9.

[0379] In another embodiment, a liquid nutritional composition is provided, wherein each 100 ml of the liquid nutritional composition comprises:

[0380] i) 1 to 15 mg, preferably 1.5 to 14 mg, more preferably 2 to 13 mg coenzyme Q10;

[0381] (ii) 1.5 to 10 μg, preferably 2 to 9 μg, more preferably 2.5 to 8 μg vitamin D, preferably vitamin D3;

[0382] (iii) 0.1 to 1.4 mg, preferably 0.2 to 1.2 mg, more preferably 0.3 to 1 mg vitamin B2;

[0383] (iv) 30 to 240 mg, preferably 35 to 220 mg, more preferably 40 to 200 mg DHA; and / or

[0384] 70 to 440 mg, preferably 80 to 420 mg, more preferably 90 to 400 mg EPA;

[0385] (v) 35 to 170 mg, preferably 40 to 160 mg, more preferably 45 to 150 mg choline, wherein the choline is selected from free choline, choline salts and / or choline esters, preferably at least phosphatidylcholine, wherein the composition preferably comprises v a ) phosphatidylcholine and v b ) choline or a salt thereof, wherein the weight ratio of phosphatidylcholine to choline is greater than 0.1;

[0386] and at least one of (vi) and (vii);

[0387] (vi) 0.2 to 1 mg, preferably 0.25 to 0.8 mg, more preferably 0.3 to 0.7 mg vitamin B6;

[0388] (vii) 20 to 225 μg, preferably 25 to 200 μg, more preferably 30 to 175 μg vitamin B9.

[0389] In a further preferred embodiment, the liquid nutritional composition comprising at least one of (i) and (ii), (iii), (vi) and (vii), and optionally a combination of (iv) and / or (v) further comprises one or more of the following per 100 ml:

[0390] (viii) 50 to 400 μg, preferably 75 to 350 μg, more preferably 100 to 300 μg retinol equivalent vitamin A;

[0391] (ix) 0.1 to 0.9 mg, preferably 0.15 to 0.8 mg, more preferably 0.2 to 0.75 mg vitamin B1;

[0392] (x) 0.5 to 3 μg, preferably 0.6 to 2.6 μg, more preferably 0.7 to 2.4 μg vitamin B12;

[0393] (xi) 10 to 100 mg, preferably 15 to 90 mg, more preferably 20 to 80 mg vitamin C;

[0394] (xii) 2 to 14 mg, preferably 2.5 to 12 mg, more preferably 2.75 to 10 mg α-TE;

[0395] (xiii) 8 to 45 μg, preferably 10 to 40 μg, more preferably 11 to 35 μg selenium; and

[0396] (xiv) 20 to 160 mg, preferably 25 to 150 mg, more preferably 30 to 140 mg magnesium.

[0397] In another preferred embodiment, the liquid nutritional composition may further contain one or more of the following per 100 ml:

[0398] (xv) 1.2 to 6 mg, preferably 1.4 to 5.5 mg, more preferably 1.6 to 5 mg vitamin B3 (niacin equivalent);

[0399] (xvi) 0.3 to 2.2 mg, preferably 0.4 to 2 mg, more preferably 0.5 to 1.8 mg vitamin B5;

[0400] (xvii) 2 to 14 mg, preferably 3 to 12 mg, more preferably 3.5 to 11 mg of vitamin B7;

[0401] The present invention further provides a liquid nutritional composition, wherein the liquid nutritional composition comprises per 100 kcal:

[0402] (i) 1.5 to 5.5 mg, preferably 1.8 to 5.2 mg, more preferably 2 to 5 mg coenzyme Q10;

[0403] (ii) 1.3 to 4.5 μg, preferably 1.5 to 4 μg, more preferably 2 to 3.5 μg vitamin D, preferably vitamin D3;

[0404] (iii) 0.4 to 0.6 mg, preferably 0.15 to 0.5 mg, more preferably 0.2 to 0.4 mg vitamin B2;

[0405] and optionally

[0406] (iv) 20 to 100 mg, preferably 25 to 90 mg, more preferably 30 to 80 mg DHA; and / or

[0407] 20 to 225 mg, preferably 60 to 200 mg, more preferably 70 to 170 mg EPA; and / or

[0408] (v) 100 to 1000 mg, preferably 200 to 800 mg, more preferably 300 to 500 mg choline or a choline salt.

[0409] The present invention also provides a liquid nutritional composition, wherein the liquid nutritional composition comprises per 100 kcal:

[0410] (i) 1.5 to 5.5 mg, preferably 1.8 to 5.2 mg, more preferably 2 to 5 mg coenzyme Q10;

[0411] (ii) 1.3 to 4.5 μg, preferably 1.5 to 4 μg, more preferably 2 to 3.5 μg vitamin D, preferably vitamin D3;

[0412] (iii) 0.4 to 0.6 mg, preferably 0.15 to 0.5 mg, more preferably 0.2 to 0.4 mg vitamin B2;

[0413] and optionally

[0414] (iv) 20 to 100 mg, preferably 25 to 90 mg, more preferably 30 to 80 mg DHA; and / or

[0415] 20 to 225 mg, preferably 60 to 200 mg, more preferably 70 to 170 mg EPA; and / or

[0416] (v) 100 to 1000 mg, preferably 200 to 800 mg, more preferably 300 to 500 mg choline, wherein the choline is selected from free choline, choline salts and / or choline esters, preferably at least phosphatidylcholine, wherein the composition preferably comprises v a ) phosphatidylcholine and v b ) choline or a salt thereof, and wherein the weight ratio of phosphatidylcholine to choline is greater than 0.1.

[0417] In an embodiment, a liquid nutritional composition is provided, wherein the liquid nutritional composition comprises per 100 kcal:

[0418] (i) 1.5 to 5.5 mg, preferably 1.8 to 5.2 mg, more preferably 2 to 5 mg coenzyme Q10;

[0419] (ii) 1.3 to 4.5 μg, preferably 1.5 to 4 μg, more preferably 2 to 3.5 μg vitamin D, preferably vitamin D3;

[0420] (iii) 0.4 to 0.6 mg, preferably 0.15 to 0.5 mg, more preferably 0.2 to 0.4 mg vitamin B2;

[0421] (iv) 20 to 100 mg, preferably 25 to 90 mg, more preferably 30 to 80 mg DHA; and / or

[0422] 20 to 225 mg, preferably 60 to 200 mg, more preferably 70 to 170 mg EPA;

[0423] (v) 100 to 1000 mg, preferably 200 to 800 mg, more preferably 300 to 500 mg choline.

[0424] In an embodiment, a liquid nutritional composition is also provided, wherein the liquid nutritional composition comprises per 100 kcal:

[0425] (i) 1.5 to 5.5 mg, preferably 1.8 to 5.2 mg, more preferably 2 to 5 mg coenzyme Q10;

[0426] (ii) 1.3 to 4.5 μg, preferably 1.5 to 4 μg, more preferably 2 to 3.5 μg vitamin D, preferably vitamin D3;

[0427] (iii) 0.4 to 0.6 mg, preferably 0.15 to 0.5 mg, more preferably 0.2 to 0.4 mg vitamin B2;

[0428] (iv) 20 to 100 mg, preferably 25 to 90 mg, more preferably 30 to 80 mg DHA; and / or

[0429] 20 to 225 mg, preferably 60 to 200 mg, more preferably 70 to 170 mg EPA;

[0430] (v) 100 to 1000 mg, preferably 200 to 800 mg, more preferably 300 to 500 mg choline, wherein the choline is selected from free choline, choline salts and / or choline esters, preferably at least phosphatidylcholine, wherein the composition preferably comprises v a ) phosphatidylcholine and v b ) choline or a salt thereof, and wherein the weight ratio of phosphatidylcholine to choline is greater than 0.1.

[0431] In an embodiment, the liquid nutritional composition comprises per 100 kcal:

[0432] (i) 1.5 to 5.5 mg, preferably 1.8 to 5.2 mg, more preferably 2 to 5 mg coenzyme Q10;

[0433] (ii) 1.3 to 4.5 μg, preferably 1.5 to 4 μg, more preferably 2 to 3.5 μg vitamin D, preferably vitamin D3;

[0434] and optionally

[0435] (iv) 20 to 100 mg, preferably 25 to 90 mg, more preferably 30 to 80 mg DHA; and / or

[0436] 20 to 225 mg, preferably 60 to 200 mg, more preferably 70 to 170 mg EPA; and / or

[0437] (v) 100 to 1000 mg, preferably 200 to 800 mg, more preferably 300 to 500 mg choline or a choline salt.

[0438] In another embodiment, a liquid nutritional composition is provided, the liquid nutritional composition comprising per 100 kcal:

[0439] (i) 1.5 to 5.5 mg, preferably 1.8 to 5.2 mg, more preferably 2 to 5 mg coenzyme Q10;

[0440] (ii) 1.3 to 4.5 μg, preferably 1.5 to 4 μg, more preferably 2 to 3.5 μg vitamin D, preferably vitamin D3;

[0441] (iii) 0.4 to 0.6 mg, preferably 0.15 to 0.5 mg, more preferably 0.2 to 0.4 mg vitamin B2; in combination with at least one of (vi) and (vii);

[0442] (vi) 0.1 to 0.5 mg, preferably 0.2 to 0.4 mg, more preferably 0.25 to 0.3 mg vitamin B6;

[0443] (vii) 16 to 80 μg, preferably 18 to 75 μg, more preferably 20 to 70 μg vitamin B9;

[0444] and optionally

[0445] (iv) 20 to 100 mg, preferably 25 to 90 mg, more preferably 30 to 80 mg DHA; and / or

[0446] 20 to 225 mg, preferably 60 to 200 mg, more preferably 70 to 170 mg EPA; and / or

[0447] (v) 100 to 1000 mg, preferably 200 to 800 mg, more preferably 300 to 500 mg choline, choline salts and / or choline esters.

[0448] In another preferred embodiment, the liquid nutritional composition comprises at least one of (i), (ii) and (iii), (vi) and (vii) and optionally a combination of (iv) and / or (v) per 100 kcal, and further comprises one or more of the following:

[0449] (viii) 60 to 150 μg, preferably 70 to 140 μg, more preferably 80 to 130 μg retinol equivalent vitamin A;

[0450] (ix) 0.05 to 0.4 mg, preferably 0.1 to 0.35 mg, more preferably 0.15 to 0.30 mg vitamin B1;

[0451] (x) 0.4 to 1.4 μg, preferably 0.5 to 1.2 μg, more preferably 0.6 to 1 μg vitamin B12;

[0452] (xi) 12 to 40 mg, preferably 14 to 35 mg, more preferably 16 to 32 mg vitamin C;

[0453] (xii) 1 to 5.5 mg, preferably 1.5 to 5 mg, more preferably 2 to 4.5 mg α-TE;

[0454] (xiii) 4 to 18 μg, preferably 6 to 16 μg, more preferably 8 to 14 μg selenium; and

[0455] (xiv) 10 to 70 mg, preferably 15 to 65 mg, more preferably 20 to 60 mg magnesium.

[0456] In another preferred embodiment, the liquid nutritional composition may further contain one or more of the following per 100 kcal:

[0457] (xv) 1 to 2.5 mg, preferably 1.1 to 2.2 mg, more preferably 1.2 to 2 mg vitamin B3 (niacin equivalent);

[0458] (xvi) 0.2 to 1 mg, preferably 0.3 to 0.9 mg, more preferably 0.4 to 0.8 mg vitamin B5;

[0459] (xvii) 1.5 to 6 mg, preferably 2 to 5.5 mg, more preferably 2.5 to 5 mg of vitamin B7;

[0460] In a specific embodiment, a composition is provided, comprising

[0461] (i) Coenzyme Q10;

[0462] (ii) vitamin D, preferably vitamin D3;

[0463] (iii) Vitamin B2;

[0464] (iv) DHA and EPA;

[0465] (v) choline or a choline salt;

[0466] (vi) Vitamin B6;

[0467] (vii) Vitamin B9;

[0468] And at least one or more of the following ingredients:

[0469] (viii) retinol equivalents of vitamin A;

[0470] (ix) vitamin B1;

[0471] (x) Vitamin B12;

[0472] (xi) vitamin C;

[0473] (xii) α-TE;

[0474] (xiii) selenium; and

[0475] (xiv) Magnesium.

[0476] In another specific embodiment, a composition is provided, comprising:

[0477] (i) Coenzyme Q10;

[0478] (ii) vitamin D, preferably vitamin D3;

[0479] (iii) Vitamin B2;

[0480] (iv) DHA and EPA;

[0481] (v) choline, choline salts and / or choline esters, preferably at least phosphatidylcholine;

[0482] (vi) Vitamin B6;

[0483] (vii) Vitamin B9;

[0484] And at least one or more of the following ingredients:

[0485] (viii) retinol equivalents of vitamin A;

[0486] (ix) vitamin B1;

[0487] (x) Vitamin B12;

[0488] (xi) vitamin C;

[0489] (xii) α-TE;

[0490] (xiii) selenium; and

[0491] (xiv) Magnesium.

[0492] Examples

[0493] Example 1

[0494] An exemplary enteral tube feed is formulated containing 128 kcal per 100 ml and 4.88 g protein, 4.5 g lipid and 9.3 g carbohydrate per 100 kcal. The tube feed contains ingredients according to Table 1 and is intended for tube administration to a patient following an ischemic stroke.

[0495]

[0496]

[0497] Example 2

[0498] An exemplary oral nutritional supplement was formulated containing 240 kcal per 100 ml and 6 g protein, 3.89 g lipid and 9.57 g carbohydrate per 100 kcal. The nutritional supplement contained ingredients according to Table 2 and was intended to be administered to a patient as a drink after an ischemic stroke.

[0499]

[0500]

[0501] Example 3 - Neurite Outgrowth Using Coenzyme Q10, Vitamin D3 and Vitamin B2

[0502] Neuroreparative effects of nutrient supplementation after hypoxia.

[0503] Cortical neuron cultures

[0504] Mouse primary cortical neurons (E14) were seeded onto 96-well plates coated with poly-D-lysine. Cells (20.000 cells / well) were cultured in modified neurobasal medium (containing B27, Pen / Strep and GlutaMAX). Cell cultures were incubated at 37°C in 5% CO2, and the medium was changed every 2-3 days.

[0505] Hypoxia: oxygen glucose deprivation in vitro

[0506] On the second day of in vitro culture, cells were subjected to oxygen glucose deprivation (OGD) for 3.5 hours. To induce glucose deprivation, modified neurobasal medium was replaced with an equal volume of HBSS. For hypoxia, cells were placed in a humidity-controlled incubator (Whitley H35 hypoxia workstation) set at 0.5% O2, 94.5% N2, and 5% CO2 at 37°C for 3.5 hours. After the hypoxic incubation period, HBSS was removed and replaced with modified neurobasal medium, and the plate was returned to normoxic conditions and incubated for another 24 hours at 37°C in 5% CO2.

[0507] Nutrient Supplementation

[0508] The effects of nutrient supplementation of neuronal cultures after hypoxia were evaluated by comparing different concentrations of vitamin D3 (30 nM), coenzyme Q10 (3 μM), or vitamin B2 (30 nM) to vehicle control (0 μM). Nutrient supplementation alone, in two combinations, or in three combinations, started immediately after OGD and continued for another 24 hours. Each condition was tested in triplicate. Control cells were exposed to hypoxia but not supplemented with any of vitamin D3, B2, or coenzyme Q10.

[0509] Neurite outgrowth: immunohistochemistry and imaging

[0510] At the end of the experiment, the plate was fixed with PFA at room temperature for 5 minutes. Then, the cells were permeabilized and blocked with PBS containing 10% normal goat serum, 0.1% sodium azide and 0.2% Triton X-100. Cells were stained overnight with monoclonal anti-β-tubulin III antibody (Sigma Aldrich, T8578). Next, cells were stained with secondary antibody Alexa Fluor 488 goat anti-mouse IgG (H+L) (Invitrogen A11001 Fisher, 10256302). Cell nuclei were stained with Hoechst 33342 (Thermofisher, H3570). Images were taken with a magnification of 20× in 12 visual fields using a high content cell imaging analysis system (In Cell Analyser 2000). Quantification of neurite outgrowth was performed using InCell Developer Toolbox v1.6 software (GE Healthcare).

[0511] result

[0512] Image analysis of neurite outgrowth after hypoxia showed that supplementation with vitamin D3, vitamin B2, or coenzyme Q10 alone did not affect neurite outgrowth compared to control. However, when vitamin D3 and coenzyme Q10 were combined, increased neurite outgrowth relative to control (set to 100%) was observed. When vitamin B2 and coenzyme Q10 were combined, a similar increase in neurite outgrowth relative to control was observed. These results are depicted in Figure 1 middle.

[0513] Example 4 - Neurite Outgrowth Using Coenzyme Q10, Vitamin D3, Vitamin B6 and B9

[0514] Neuroreparative effects of nutrient supplementation after hypoxia.

[0515] Cortical neuron cultures

[0516] Primary rat cortical neurons (E18) were seeded onto 96-well plates coated with poly-D-lysine. Cells (20.000 cells / well) were cultured in neurobasal medium (containing B27, Pen / Strep and GlutaMAX). Cell cultures were incubated at 37°C in 5% CO2, and the medium was changed every 3-4 days.

[0517] Hypoxia: oxygen glucose deprivation in vitro

[0518] On the 7th day of in vitro culture, cells were subjected to oxygen glucose deprivation (OGD) for 3.5 hours. In order to induce glucose deprivation, modified neurobasal medium was replaced with neurobasal medium without glucose. For hypoxia, cells were placed in a hypoxic culture chamber (Stemcell Technologies) set at 0.1% O2, 94.9% N2 and 5% CO2 at 37°C for 3.5 hours. After the hypoxic incubation period, the culture medium was removed and replaced with modified neurobasal medium, and the plate was restored to normoxic conditions and incubated for another 24 hours at 37°C in 5% CO2.

[0519] Nutrient Supplementation

[0520] Nutrient supplementation of neuronal cultures after hypoxia was evaluated by comparing different concentrations of vitamin D (150nM), coenzyme Q10 (15μM), vitamin B6 (1.5μM) or vitamin B9 (2.25μM) with vehicle control (0μM). Nutrients were supplemented alone, in two combinations or in three combinations, starting 24h after OGD and continuing for two days. Each condition was tested in 5 replicates. Control cells were exposed to hypoxia but not supplemented with any of vitamin D, B6, B9 or coenzyme Q10.

[0521] Neurite outgrowth: immunohistochemistry and imaging

[0522] At the end of the experiment, the plate was fixed with 4% PFA for 15 minutes at room temperature. Then, the cells were permeabilized and blocked with an antibody buffer containing 20% ​​normal goat serum and 0.2% Triton X-100. The cells were stained overnight with a polyclonal anti-MAP2 antibody (Novusbio, NB300-213). Next, the cells were stained with a secondary antibody CF-4A88 goat anti-chicken IgY (H+L) (Sigma, SAB4600039). The nuclei were stained with Hoechst33342 (Thermo Scientific, #62249). Images were taken at a magnification of 10× in 9 fields of view using the ImageExpressMicroConfocal confocal high-content imaging system (Molecular Devices). MetaExpress software (Molecular Devices) was used to quantify the outgrowth of neurites.

[0523] result

[0524] Image analysis of neurite outgrowth following hypoxia showed that supplementation with individual nutrients did not affect neurite outgrowth compared to control. However, when vitamin D3 and coenzyme Q10 were combined, increased neurite outgrowth relative to control was observed. Similar results were observed when coenzyme Q10 was combined with either vitamin B9 or vitamin B6. When the three nutrients were combined, neurite outgrowth was increased even more compared to single and dual combinations of the nutrients, with this effect being highest when combining vitamin D3, coenzyme Q10, and vitamin B6. These results are depicted in Figure 2 (Vitamin D3 + Coenzyme Q10 + Vitamin B9 or Vitamin B6).

[0525] Example 5 - Neurite Outgrowth Using Coenzyme Q10, Vitamin D3, Vitamin B2, PUFA and Choline Sources

[0526] The effects of nutrient supplementation on neurite outgrowth parameters in PC12 pheochromocytoma cells were also evaluated. PC12 neurite outgrowth is one of the most widely used cell models to study neuronal differentiation.

[0527] Increased strength of neurite outgrowth may have a positive role in supporting functional brain connectivity and aid in functional recovery, particularly after stroke. Any improvement in neurite outgrowth, as observed in the PC12 cell study, could lead to improvements in those parts of the brain affected by stroke.

[0528] Materials and Methods

[0529] PC12 pheochromocytoma cells were grown in DMEM (Gibco) supplemented with 10% fetal bovine serum (FBS), penicillin (100 units / ml) and streptomycin (100 μg / ml) (Gibco) at 37° C. in a humidified atmosphere with 95% air and 5% CO 2. Cells were seeded at a density of 5000 cells / well on 96-well plates coated with collagen (0.01 mg / ml) and supplemented 24 hours later with medium containing 20 ng / ml nerve growth factor (NGF) with or without coenzyme Q10 (1 μM), vitamin D3 (0.25 μM), vitamin B2 (0.5 μM), DHA (6.7 μM), a choline source (20 μM, phosphatidylcholine, PC) or a mixture thereof.

[0530] In PC12 experiments, cells were not exposed to hypoxia.

[0531] Docosahexaenoic acid (DHA) was resuspended in absolute ethanol and diluted 5-fold in fetal bovine serum. All compounds were purchased from Sigma (Zwijndrecht, The Netherlands).

[0532] Cells were supplemented in 96-well plates in 6 replicates. These conditions were compared with unsupplemented cells. After 48 hours of supplementation with these combinations, cells were stained with calcein-AM dye (2ng / μl) in 100μl culture medium per well, and the nuclei were counterstained with Hoechst dye (0.6μg / ml), and incubated at 37°C for 20min. Subsequently, FITC and DAPI images were taken using the ImageXpress high-content imaging system (9 images per well for 96-well plates). The length of neurites was quantified using the neurite outgrowth module in MetaXpress.

[0533] When Coenzyme Q10, Vitamin D3, Vitamin B2, DHA and PC were combined, increased neurite outgrowth was observed relative to the control (set as 100%). The neurite outgrowth observed using the combination of all 5 evaluated compounds resulted in a greater than additive effect on neurite outgrowth compared to the control (calculated or expected average neurite outgrowth was 152, observed average neurite outgrowth was 157). The results are depicted in Figure 3 middle.

[0534] In the PC12 model, the combination of the five components provided a synergistic increase in neurite outgrowth from these cells.

[0535] Example 6 - Neurite Outgrowth Using Choline and / or Phosphatidylcholine

[0536] Experiments similar to those described in Example 5 above were performed, wherein the effects of different ratios of choline in the form of choline chloride and phosphatidylcholine at similar total choline concentrations per condition on neurite outgrowth were evaluated compared to unsupplemented control PC12 cells (set as 100%).

[0537] Nutrients were supplemented alone (100 chol-Cl or 100% PC) and at ratios of 60:40 and 40:60 chol-Cl to PC. Cells were supplemented with choline derived from chol-Cl, PC, or both at a total concentration of 20 μM in 96-well plates in six replicates. Neuronal outgrowth under these conditions was compared to unsupplemented PC12 cells.

[0538] result

[0539] Image analysis of neurite outgrowth showed that supplementation with 100% PC increased neurite outgrowth slightly more than supplementation with 100% chol-Cl compared to neurite outgrowth of unsupplemented control PC12 cells. Chol-Cl:PC ratios between 60:40 and 40:60 showed similar improvements in neurite outgrowth as PC12 cells supplemented with 100% chol-Cl. These results are depicted in Figure 4 middle.

[0540] The results suggest that, at the same choline concentration, choline provided in the form of PC may have a slightly better effect on neurite outgrowth than choline chloride. Using a mixture with at least 40% PC achieved effects comparable to the 100% PC condition.

Claims

1. A nutritional composition for use in the treatment of stroke, preferably ischemic stroke, comprising a combination of (i) coenzyme Q10, (ii) vitamin D and (iii) vitamin B2.

2. The nutritional composition for use according to claim 1, wherein the composition further comprises (iv) polyunsaturated fatty acids and (v) choline, preferably (iv) polyunsaturated fatty acids selected from DHA, EPA and / or DPA and (v) choline.

3. Nutritional composition for use according to any one of claims 1 and 2, wherein choline is provided in the form of free choline, a choline salt and / or a choline ester, wherein the choline ester is preferably phosphatidylcholine.

4. The nutritional composition for use according to any one of claims 1 to 3, wherein the composition further comprises one or more of (vi) vitamin B6 and (vii) vitamin B9.

5. Nutritional composition for use according to any one of claims 1 to 4, wherein the treatment of stroke comprises treating and / or preventing consequences associated with said stroke in a subject suffering from said stroke.

6. The nutritional composition for use according to any one of the preceding claims, wherein the treatment of stroke comprises an increase in the length of neurite outgrowth of neurons in a subject having a stroke and treated with the composition compared to a subject having a stroke and not treated with the composition.

7. The nutritional composition for use according to any of the preceding claims, wherein the treatment of stroke comprises preventing or ameliorating a functional consequence associated with stroke selected from any of hemiparesis, hemi-esthesia, language or visuospatial deficits, and wherein a subject suffering from a stroke and treated with the composition has an improvement in functional consequence associated with stroke compared to a subject suffering from a stroke and not treated with the composition.

8. Nutritional composition for use according to any of the preceding claims, wherein the composition is used for at least 2 weeks, preferably at least 4 weeks after diagnosis of stroke.

9. A nutritional composition for use according to any one of the preceding claims, wherein the composition comprises a daily dose of: (i) 8 to 80 mg, preferably 10 to 70 mg, more preferably 15 to 60 mg coenzyme Q10; (ii) 6 to 75 μg, preferably 8 to 70 μg, more preferably 10 to 65 μg vitamin D, preferably vitamin D3; (iii) Vitamin B2 in the range of 0.8 to 7.6 mg, preferably 1 to 7.4 mg, more preferably 1.2 to 7.2 mg and optionally (iv) 150 to 1200 mg, preferably 200 to 1100 mg, more preferably 250 to 1000 mg DHA; and / or 300 to 2400 mg, preferably 400 to 2200 mg, more preferably 500 to 2000 mg / day of EPA; and / or (v) 200 to 1400 mg, preferably 300 to 1200 mg, more preferably 350 to 1100 mg choline.

10. A nutritional composition for use according to any one of the preceding claims, further comprising one or more selected from vitamins A, C and E, phospholipids, selenium, magnesium and further B vitamins.

11. A nutritional composition for use according to any one of the preceding claims, wherein the composition comprises v a ) phosphatidylcholine and v b ) choline or a salt thereof, and wherein the weight ratio of phosphatidylcholine to choline is greater than 0.

1.

12. Nutritional composition for use according to the preceding claims, wherein the nutritional composition is a liquid nutritional composition.

13. The nutritional composition for use according to the preceding claim, wherein the nutritional composition is an oral nutritional supplement or a tube feed.

14. A liquid nutritional composition comprising a combination of: (i) Coenzyme Q10; (ii) vitamin D, preferably vitamin D3; (iii) vitamin B2, and; Optionally (iv) a polyunsaturated fatty acid selected from DHA, EPA and / or DPA, more preferably DHA and / or EPA; and (v) choline, choline salts and / or choline esters; and optionally at least one of (vi) vitamin B6 and (vii) vitamin B9.

15. The liquid nutritional composition according to claim 14, wherein the composition Each 100kcal contains (i) 1.5 to 5.5 mg coenzyme Q10; (ii) 1.3 to 4.5 μg vitamin D, preferably vitamin D3; (iii) 0.4 to 0.6 mg vitamin B2; Optionally further comprising (iv) 20 to 100 mg, preferably 25 to 90 mg, more preferably 30 to 80 mg DHA; and / or 20 to 225 mg, preferably 60 to 200 mg, more preferably 70 to 170 mg EPA; and / or (v) 100 to 1000 mg, preferably 200 to 800 mg, more preferably 300 to 500 mg choline, choline salts and / or choline esters and optionally at least one of (vi) and (vii); (vi) 0.1 to 0.5 mg vitamin B6; (vii) 16 to 80 μg of vitamin B9.

16. The liquid nutritional composition according to any one of claims 14 and 15, wherein the composition further comprises one or more selected from vitamin A, additional vitamins B, C, E and K, phospholipids, selenium and magnesium.

17. The liquid nutritional composition according to any one of claims 14 to 16, wherein the composition further comprises one or more of the following per 100 kcal: (viii) 60 to 150 μg retinol equivalents of vitamin A; (ix) 0.05 to 0.4 mg vitamin B1; (x) 0.4 to 1.4 μg vitamin B12; (xi) 12 to 40 mg vitamin C; (xii) 1 to 5.5 mg α-TE; (xiii) 4 to 18 μg of selenium; and (xiv) 10 to 70 mg magnesium.

18. The liquid nutritional composition according to any one of claims 14 to 17, wherein the composition further comprises one or more of the following per 100 kcal: (xv) 1 to 2.5 mg vitamin B3; (xvi) 0.2 to 1 mg vitamin B5; (xvii) 1.5 to 6 mg vitamin B7.

19. The liquid nutritional composition according to any one of claims 14 to 18, wherein the composition comprises phosphatidylcholine and choline, and wherein the weight ratio of phosphatidylcholine to choline is greater than 0.

1.

20. Liquid nutritional composition according to any one of claims 14 to 19, wherein the composition has a caloric density between 1.0 and 2.5 kcal / ml, preferably between 1.2 and 2.4 kcal / ml.

21. Liquid nutritional composition according to claims 14 to 20, wherein the composition comprises 4 to 7 g protein / 100 kcal, 3 to 5.5 g lipid / 100 kcal and 8.5 to 10.5 g carbohydrate / 100 kcal.

Images