Nutritional composition linked to brain myelination, brain structure, cognition and learning in typically developing school age children

Abstract

The present invention relates to a combination of hexadecenoic acid and sphingomyelin and to a nutritional composition comprising such a combination for use in improving cognition and / or learning in a subject. The present invention also relates to a synthetic nutritional composition comprising hexadecenoic acid and sphingomyelin in specific amounts. The present invention further relates to uses and methods for improving cognition and / or learning in a subject.

Description

[0001] Nutritional composition linked to brain myelination, brain structure, cognition and learning in typically developing school age children

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a combination of hexadecenoic acid and sphingomyelin, and to a nutritional composition comprising such a combination, for use in improving cognition and / or learning in a subject, preferably a school age subject. The present invention also relates to a synthetic nutritional composition comprising hexadecenoic acid and sphingomyelin in specific amounts. The present invention further relates to uses and methods for improving cognition and / or learning in a subject in improving brain development (myelination) and brain structural connectivity.

[0004] BACKGROUND OF THE INVENTION

[0005] Child and early adolescence (5-15 years old), typically span the school age period, that is one of the most dynamic periods in brain maturation and functioning, building foundation for healthy cognition and learning, optimal development, and later success in life. Specifically, this time is characterized by rapid and dynamic brain changes that involve both brain function and structure, which are fundamental for cognition and learning. This developmental phenomenon places exceptionally high demands on the supply of key nutrients to a child. Failure to meet these nutrient demands during this crucial period may result in sub-optimal brain development and functioning, that can lead to difficulties in learning and cognitive performance.

[0006] In particular, one of the key biological processes supporting brain development, shown to be impacted by nutritional factors, is myelination. Myelination refers to the process by which naked axons are sheathed in myelin, or lipid rich insulating sheet that insulates axons and facilitates thus the transduction of the electrical signaling in the brain. This process plays a central role in determining brain structure and brain connectivity. Specifically, the amount, temporal and / or spatial distribution of white matter or structural organization in the brain. It has been shown that the rate of myelination in childhood and early adolescence is significantly correlated with efficiency of white matter connectivity. In other words, myelination affects brain connectivity, or neural pathways and how quickly and efficiently, messages in the form of neural impulses are communicated across the brain and between different brain regions. Furthermore, studies have shown that the maturation of white matter supports the establishment of neural networks essential for cognition and learning (O'Muircheartaigh J, Dean DC 3rd, Ginestet CE, Walker L, Waskiewicz N, Lehman K, Dirks H, Piryatinsky I, Deoni SC. White matter development and early cognition in babies and toddlers. Hum Brain Mapp. 2014 Sep;35(9):4475-87. doi: 10.1002 / hbm.22488. Epub 2014 Feb 27. PMID: 24578096; PMCID: PMC4336562. Xiongtao Dai, Hans-Georg Muller, Jane-Ling Wang & Sean C. L. Deoni. Age-dynamic networks and functional correlation for early white matter myelination. Brain Structure and Function. Volume 224, pages 535-551, (2019)).

[0007] While nutrient recommendations are typically targeted at overall health and development, very limited longitudinal data exists for brain benefits during development beyond 5 years of age. Nutritional deficiencies, including iron, vitamin B12, and folate, have been associated with hypomyelination, altered myelin composition, or decreased myelin synthesis. Observational studies suggest early life differences between formula-fed and breast-fed infants in fatty acid related white matter composition as well as in myelination and cognitive abilities, possibly linked to long-chain poly-unsaturated fatty acids (LC-PUFA), sphingomyelin (SM), iron and folic acid levels in infant nutrition. (Schneider N, Hauser J, Oliveira M, et al. Sphingomyelin in Brain and Cognitive Development: Preliminary Data. eNeuro. 2019;6(4):ENEURO.0421-18.2019. Published 2019 Aug 6. doi:10.1523 / ENEUR0.0421- 18.2019). The role of polar lipids in neurodevelopment, possibly via myelination has been reviewed in (Zheng L, Fleith M, Giuffrida F, O'Neill BV, Schneider N. Dietary Polar Lipids and Cognitive Development: A Narrative Review. Adv Nutr. 2019 Nov l;10(6):1163-1176. doi: 10.1093 / advances / nmz051. PMID: 31147721; PMCID: PMC6855982.). In our own past work (Hauser J, Sultan S, Rytz A, Steiner P, Schneider N. A blend containing docosahexaenoic acid, arachidonic acid, vitamin B12, vitamin B9, iron and sphingomyelin promotes myelination in an in vitro model. Nutr Neurosci. 2020 Dec;23(12):931-945. doi:

[0008] 10.1080 / 1028415X.2019.1580918. Epub 2019 Feb 26. PMID: 30806182), we found that in vitro treatment with a blend of docosahexaenoic acid (DHA), arachidonic acid (ARA), vitamin B12, folic acid, iron and sphingomyelin in a primary cell culture model increased the number of oligodendrocyte precursor cells, their differentiation and maturation.

[0009] The impact of some nutrients and their compositions on promoting overall brain myelination in infancy and toddlerhood are known. Nutritional composition and infant formula promoting myelination of the overall brain is described in patent documents W02017102710, W02017102712, W02017102714, W02017102715, W02017102717, W02017102718,

[0010] W02017102719, W02017102720, W02017108500, WO2017167415, WO2017167416,

[0011] WO2017167417, WO2017167419, WO2017167420, WO2017167895, WO2017167896,

[0012] WO2017167897, WO2017167898, WO2017167899.

[0013] While recent studies (Schneider et al., Child Development: 2022: 93: 359-371) revealed that changes in myelination, specifically amount of myelin, in specific brain regions during brain development at different ages is associated with socio-emotional development, very little is known for school age. In short, the vast majority of studies investigating the relationship between nutrition and brain development have focused on early life (0-5 years old), or deficiency studies (i.e. nutritional intervention in malnutrition or disadvantaged groups).

[0014] Given that school age has been identified as a very sensitive and dynamic period of both physical, neural, and cognitive growth (Huffman, S.L., Harika, R.K., Eilander, A. and Osendarp, S.J.M. (2011), Essential fats: how do they affect growth and development of infants and young children in developing countries? A literature review. Maternal & Child Nutrition, 7: 44-65. https: / / doi.Org / 10.llll / i.1740-8709.2011.00356.x, Philippa A. Jackson, Jonathon L. Reay, Andrew B. Scholey, David O. Kennedy, Docosahexaenoic acid-rich fish oil modulates the cerebral hemodynamic response to cognitive tasks in healthy young adults, Biological Psychology, Volume 89, Issue 1, 2012, Pages 183-190, https: / / doi.Org / 10.1016 / j.biopsycho.2011.10.006.), it is paramount to understand how optimal nutrition can support myelination, brain structure (or white matter connectivity), cognition and learning during this period.

[0015] Accordingly, there is a need to identify nutrients necessary to promote age-dependent brain development, more specifically myelination and white matter connectivity, in brain regions that support cognition and learning in school age children. Further there is a need to provide age and brain stage appropriate nutritional compositions having specific ingredients for use to promote myelination and white matter connectivity across brain regions supporting cognition and learning.

[0016] Additionally, there is a need to further understand how nutritional compositions that promote myelination and white matter connectivity in brain regions supporting cognition and learning, operate on the molecular level (or mechanisms of action) and enhance learning in an in-vivo model.

[0017] The aim of the present invention is to provide optimal nutrient blend compositions having specific ingredients to promote myelination and white matter connectivity in the brain, in particular in regions associated with cognition and learning, of young individuals, in particular school age children.

[0018] SUMMARY OF THE INVENTION

[0019] The object of the present invention is achieved by the subject matter of the independent claims. The dependent claims further develop the idea of the present invention.

[0020] The inventors have surprisingly found through mediation analysis between nutritional intake, brain measures (myelin and brain connectivity), and cognition and learning in children between 2 and 14 years old, that there are significant nutrients affecting myelination and brain structure (white matter), which correlate with cognition and learning.

[0021] Specifically, mediation analyses have been performed and have demonstrated the following significant nutrient ingredients:

[0022] 1) Nutrients --> myelin --> cognition. Analysis indicates that the most significant nutritional ingredients are: hexadecenoic acid, sphingomyelin, folate and iron.

[0023] 2) Nutrients-> brain structure (white matter / structural connectivity) --> cognition. The mediation analysis has shown that the most significant nutritional ingredients are: hexadecenoic acid, sphingomyelin, DHA and choline.

[0024] 3) Nutrients-> myelin --> learning (measured with reading skills). The mediation analysis has shown that the most significant nutritional ingredients are: hexadecenoic acid, sphingomyelin, Vitamin B12 and iron.

[0025] 4) Nutrients-> brain structure (white matter / structural connectivity) --> learning (measured with reading skills). The mediation analysis has shown that the most significant nutritional ingredients are: hexadecenoic acid, sphingomyelin, lutein and zeaxanthin, and choline.

[0026] In a first aspect, the present invention provides a nutritional composition comprising hexadecenoic acid and sphingomyelin, for use in improving cognition and / or learning in a subject.

[0027] In a second aspect, the present invention provides a nutritional composition comprising hexadecenoic acid and sphingomyelin.

[0028] In a third aspect, the present invention provides a non-therapeutic method for improving cognition and / or learning in a school age child, the method comprising administering to said child an effective amount of hexadecenoic acid and sphingomyelin.

[0029] In a fourth aspect, the present invention provides the use of hexadecenoic acid and sphingomyelin, in the manufacture of a nutritional composition for improving cognition and / or learning in a school age child.

[0030] BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1: Mediation analysis focused on the influence of nutritional intake linked to brain myelination and cognition.

[0032] Figure 2: Mediation analysis focused on the influence of nutritional intake linked to brain myelination and learning.

[0033] Figure 3: Mediation analysis focused on the influence of nutritional intake linked to white matter diffusivity, and cognition. Figure 4: Mediation analysis focused on the influence of nutritional intake linked to brain structure and learning.

[0034] Figure 5: Differences in the performance between two groups or diets (control vs M161+SM enriched diet). Here the lower the error rate (y axis) the better the group performed at the task, showing hence faster learning.

[0035] Figure 6: Viability Rate of OPCs Post-Treatment with SM, M161, and Combined SM + M161.

[0036] Figure 7: Quantification of MBP Protein Following Treatment, Normalized to Total Protein content.

[0037] DETAILED DESCRIPTION OF THE INVENTION

[0038] Definitions

[0039] The term "subject" as used herein refers to a mammal and more particularly a cat, a dog or a human. In one embodiment, the subject is a child, preferably a school age child.

[0040] The term "child" means a child aged between two and six years, including toddlers and preschool children.

[0041] The term "school age child" means a child aged between two and fifteen years old, preferably between five and fifteen years, and encompasses children in the transformative 10 (5-15 y.o.). The "ASA24" is a dietary intake questionnaire tool used to assess an individual's dietary intake. ASA24 stands for Automated Self-Administered 24-Hour Recall, and it is a web-based tool that collects detailed information about the foods and beverages consumed by an individual over a 24-hour period. The questionnaire asks participants to recall all the foods and beverages they consumed, including portion sizes and preparation methods. It also collects information on dietary supplements and medications. The ASA24 questionnaire is designed to provide researchers and healthcare professionals with accurate and comprehensive data on an individual's dietary intake for research purposes, nutritional assessment, and dietary counseling (Raffoul A, Hobin EP, Sacco JE, Lee KM, Haines J, Robson PJ, Dodd KW, Kirkpatrick SI. School-Age Children Can Recall Some Foods and Beverages Consumed the Prior Day Using the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24) without Assistance. J Nutr. 2019 Jun l;149(6):1019-1026. Doi: 10.1093 / jn / nxz013. PMID: 31006813; PMCID: PMC6698634). Nutritional intake was assessed with standardised and validated questionnaire called The Automated Self-Administered 24- hour (ASA24®) Dietary Assessment Tool, that enables multiple, automatic coded, 24-h diet recalls, also known as food diaries. Based on this, 65 nutrients and 37 food groups are extracted and then, the mediation model was calculated exploring the association between nutrients (based on daily intake). Hence this study is not based on nutritional intervention, but rather on the association of nutrients consumed daily, brain myelination and white matter connectivity, and learning and cognitive outcomes. Therefore, the relationship assessed via mediation analysis, is carried out between daily nutritional intake characterized in 65 nutrients and brain measures (myelination and brain connectivity), and learning and cognitive skills.

[0042] Within the context of the present invention, the term "cognition" refers to the mental processes and abilities involved in acquiring, processing, storing, and using information. It encompasses various cognitive functions, including verbal comprehension, visual spatial skills, fluid reasoning, working memory, and processing speed. These cognitive functions are interconnected and contribute to overall cognitive abilities and performance in various tasks and activities. Cognitive functions as described above can be measured using the Wechsler Preschool and Primary Scale of Intelligence (Wechsler D. Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) Pearson; San Antonio, TX, USA: 2012).

[0043] The term "verbal comprehension" refers to the ability to understand and use language effectively, including understanding spoken and written words, following instructions, and expressing oneself verbally.

[0044] Within the context of the present invention, white matter, brain structure, or structural connectivity are used interchangeably.

[0045] The term "visual spatial skills" refers to the ability to perceive and mentally manipulate visual information, such as recognizing patterns, understanding spatial relationships, and mentally rotating objects. The term "fluid reasoning" refers to the ability to think logically, solve problems, and draw inferences based on abstract information. It involves the capacity to identify patterns, make connections, and apply logical reasoning to new situations.

[0046] The term "working memory" refers to the cognitive system responsible for temporarily holding and manipulating information in the mind. It involves the ability to remember and process information in real-time, such as following multi-step instructions or mentally calculating math problems.

[0047] The term "processing speed" refers to the speed and efficiency with which an individual can perceive and process information. It involves the ability to quickly and accurately process visual or auditory stimuli, make decisions, and respond to tasks or stimuli.

[0048] Within the context of the present invention, the term "learning" refers to the acquisition and development of skills and knowledge in the specific areas of letter / word reading, spelling, reading comprehension, and mathematical calculation. Learning in these areas involves the acquisition, practice, and refinement of specific skills and knowledge through instruction, practice, and experience. It encompasses the development of foundational skills and the ability to apply them in various contexts and situations. Learning as described above can be measured using Academic Achievement Batteries such as described in Messer (Messer, Melissa A. Academic Achievement Battery: Comprehensive Form. PAR, 2014.)

[0049] The term "letter / word reading" refers to the ability to recognize and understand written words, including decoding and understanding the meaning of individual letters and words. It encompasses skills such as phonics, sight word recognition, and fluency in reading.

[0050] The term "spelling" refers to the ability to accurately and correctly write words, including understanding and applying spelling rules, phonics, and word patterns. It involves the knowledge of letter-sound relationships and the ability to use this knowledge to spell words correctly.

[0051] The term "reading comprehension" refers to the ability to understand and interpret written text. It involves skills such as understanding main ideas, making inferences, drawing conclusions, and evaluating information. Reading comprehension also includes the ability to engage with and critically analyze written material.

[0052] The term "mathematical calculation" refers to the ability to perform mathematical operations, such as addition, subtraction, multiplication, and division. It involves understanding numerical concepts, applying mathematical rules and procedures, and solving mathematical problems accurately and efficiently.

[0053] Within the context of the present invention, the expression "nutritional composition" refers to a composition which nourishes a subject. This nutritional composition is usually taken orally or intravenously. It may include a lipid or fat source, a carbohydrate source and / or a protein source. Moreover, "nutritional composition(s)" may refer to liquids, powders, gels, pastes, solids, concentrates, suspensions, dairy products, or ready-to-use forms of enteral formulas, oral formulas, formulas for infants, formulas for pediatric subjects, formulas for children, infant formula, a starter infant formula, a follow-on or follow-up formula, a fortifier such as a human milk fortifier, growing-up milks and / or formulas for adults, porridges and / or infant cereals, baby food, pet food, snack bars, healthy drinks, healthy snacks, smoothies, sandwiches and wraps, frozen treats or supplements.

[0054] Within the context of the present invention, the expression "synthetic nutritional composition" refers to a mixture obtained by chemical and / or biological means that can be chemically identical to the mixture naturally occurring in mammalian milk (i.e., the synthetic nutritional composition is not breast milk).

[0055] Within the context of the present invention, the term "nutrient" or "nutrients" is intended to comprise both macronutrients (for example carbohydrates, proteins or fats) and micronutrients (for example minerals or vitamins) and components thereof (e.g. fatty acids, amino acids) for the human body.

[0056] Within the context of the present invention, the terms "ingredient" or "ingredients" indicate an edible substance or mixture of substances which comprise or is essentially consisting of a nutrient for the human body. The terms "improve", "improving", "enhance", "enhancing", "promote", "promoting" and "promotion" can be used interchangeably. They should be understood as comprising support or help to the health of an individual, for example to support or help the development or growth of an individual. The individual may not suffer from a disease but may be susceptible to the development of unhealthy conditions, for example later in life.

[0057] The expression "growing-up milk (or GUM)" refers to a milk-based drink generally with added vitamins and minerals that is intended for young children or children.

[0058] The expression "milk-based beverage" refers to a milk-based drink generally with added vitamins and minerals that can be provided in a ready to drink format, or as a powder to be reconstituted.

[0059] The expression "fortifier" refers to liquid or solid nutritional composition suitable for fortifying or mixing with human breast milk, infant formula, growing-up milk or a milk-based beverage.

[0060] Within the context of the present invention the term "DHA" refers to C22:6n-3 (docosahexaenoic acid).

[0061] The term "sphingomyelin (SM)" as used herein refers to a lipid molecule, or a mixture of lipid molecules, wherein a sphingosine or a shinganine backbone is esterified with a fatty acid residue at the amino group (-NH2) through an amide bound and wherein the hydroxyl group at position 1 of the sphingosine backbone is linked to a phophorylcholine moiety.

[0062] In a particular embodiment, sphingomyelin is a compound of formula (VIII) or a mixture of compounds of formula (VIII) (VIII) wherein R14 is a C2 to C43 branched or unbranched acyclic alkyl or acyclic alkenyl group, and R15 is a C2 to C43 branched or unbranched acyclic alkyl or acyclic alkenyl group.

[0063] More particularly R14 is a C13 to C43 branched or unbranched acyclic alkyl or acyclic alkenyl group which together with the adjacent carbonyl group correspond to a C14 to C44 saturated or unsaturated fatty acid residues.

[0064] Non-limiting examples of C14 to C44 saturated or unsaturated fatty acids from which the fatty acid residue may stem include: C14:0, C15:0, C16:0, C18:0, C20:0, C21:0, C22:0, C23:0, C24:l, C25:0, C28:l, C30:2, C30:l, C30:0, C32:3, C32:2, C32:l, C32:0, C33:l, C34:3, C34:2, C34:l, C34:0, C35:2, C35:0, C36:4, C36:3, C36:2, C36:l, C36:0, C37:l, C37:0, C38:4, C38:3, C38:l, C38:0, C39:l, C39:0, C40:2, C40:l, C40:0, C41:2, C41:l, C41:0, C42:47, C42:3, C42:2, C42:l, C42:0, C44:3, C44:l.

[0065] Even more particularly R14 is a C13 to C23 branched or unbranched acyclic alkyl or acyclic alkenyl group which together with the adjacent carbonyl group is a C14 to C24 saturated or unsaturated fatty acid residue, wherein the fatty acid from which the fatty acid residue may stem is selected from the group consisting of: C14:0, C15:0, C16:0, C18:0, C20:0, C21:0, C22:0, C23:0, C24:0, C18:ln-9, C18:2n-6, and C24:ln-9.

[0066] Even more particularly still, sphingomyelin is a mixture of compounds of formula (VIII) wherein the mixture is such that the total number of fatty acid residues (R14 together with the adjacent carbonyl group) comprised in the mixture are predominately saturated fatty acids, and the least predominant are unsaturated fatty acids. More particularly the mixture will be such that 80 % to 96 % of said fatty acid residues in the mixture are saturated fatty acids, in particular C14, C15, C16, C18, C20, C22, C23, C24 saturated fatty acids, more particularly C16, C18, C20, C22 and C24.

[0067] The term "hexadecenoic acid," also known as palmitoleic acid, refers to a monounsaturated fatty acid containing 16 carbon atoms in its chain. It is classified as an omega-7 fatty acid due to the position of its double bond. Omega 7 refers to a broader class of monounsaturated fatty acids with the first double bond in the 7th position from the methyl end. Palmitoleic acid is a specific member of this family. Palmitoleic acid occurs naturally and is present in various foods. This monounsaturated fatty acid has a crucial role in myelination and brain development. It is one of the most abundant fatty acids found in the brain and is a major component of myelin, the protective sheath that surrounds neuronal axons.

[0068] Hexadecenoic acid is involved in the synthesis and maintenance of myelin by providing the necessary building blocks for the formation of myelin lipids. It is incorporated into the phospholipids and sphingolipids that make up the myelin sheath, contributing to its structural integrity and stability.

[0069] Furthermore, hexadecenoic acid is also involved in the regulation of gene expression and signaling pathways that are essential for oligodendrocyte development and myelination. It influences the differentiation and maturation of oligodendrocyte precursor cells, which are responsible for producing myelin.

[0070] Overall, hexadecenoic acid plays a vital role in myelination and brain development by providing structural support to the myelin sheath and influencing the development and function of oligodendrocytes. Adequate levels of palmitic acid (also known as C16:0, hexadecanoic fatty acid) and palmitoleic acid (hexadecenoic, monounsaturated C16:l) in the diet are important for optimal myelination and the proper functioning of the central nervous system. Dietary sources of hexadecenoic acid predominantly include various animal fats, vegetable oils such as avocado oil, and marine oils.

[0071] The term "vitamin B12" as used herein refers to an essential water-soluble vitamin that plays a crucial role in various physiological processes. Vitamin B12 is the term used to designate all compounds having the same biological activity as cyanocobalamin. It is present in nature as methyl cobalamin (MeCbl), adenosylcobalamin (AdoCbl) and hydroxycobalamin (OHCbl).

[0072] Vitamin B12 is crucial for healthy brain development, reflected through the approved EFSA claim (Vitamin B12 contributes to the normal function of the nervous system) and claim by NHCP (Vitamin B12 is essential for / supports brain connectivity). The consensus on its important role mainly comes from deficiency studies. Namely, as highlighted by EFSA (EFSA 2010), it is well established from clinical studies that vitamin B12 deficiency produces adverse neurological effects owing to demyelination in the spinal cord, brain, and optic and peripheral nerves. Furthermore, within the central nervous system, vitamin B12 is required for the metabolism of the neurotransmitter dopamine and noradrenaline. Importantly, adequate intake of vitamin B12 is vital in maintaining the integrity of the nerve's myelin sheath, allowing rapid and efficient transmission of nerve impulses (Kumar N. 2014. Neurologic aspects of cobalamin (B12) deficiency. Hand Coin Neurol, 20:915-26. doi: 10.1016 / B978-0-7020-4087- 0.00060-7 ).

[0073] The term "folate" as used herein refers to a family of compounds represented by folic acid. They are present in nature in many different forms, from which the majority is 5- methyltetrahydrofolate (5MTHF).

[0074] Vitamin B9 (Folate) is known to be one of the key vitamins necessary for healthy brain development. Folate enters the brain by an active transport mechanism followed by passive diffusion into brain cells. From the early fetal stages of the formation of the presumptive spinal cord and brain to the maturation and maintenance of the nervous system during infancy and childhood, folate levels and its supplementation have been considered influential in the clinical outcome of infants and children affected by neurological diseases. However, despite the vast epidemiological data recorded on folate function and neural tube defects, neural development and neurodegenerative diseases, the mechanism of folate action in the developing neural tissue have remained elusive (Balashova OA et al. (2018) FOLATE ACTION IN NERVOUS SYSTEM DEVELOPMENT AND DISEASE. Dev Neurobiol, 78(4): 391-402.). While most human research has focused on folate and neural tube development, no intervention trials with folate alone have been conducted in children.

[0075] The term "iron" as used herein refers to a mineral that is naturally present in many foods, added to some food products, and available as a dietary supplement. Iron is an essential component of hemoglobin, an erythrocyte (red blood cell) protein that transfers oxygen from the lungs to the tissues (Wessling-Resnick M. Iron. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler RG, eds. Modern Nutrition in Health and Disease. 11th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2014:176-88). The richest sources of heme iron in the diet include lean meat and seafood (2020-2025 Dietary Guidelines for Americans https: / / ods.od.nih.gov / About / exit_disclaimer.aspx. 9th Edition. December 2020) . Dietary sources of nonheme iron include nuts, beans, vegetables, and fortified grain products. Iron is a transition element essential for life. This metal is required to maintain the brain's biochemistry so that deficiency or excess of either copper or iron results in central nervous system disease (Madsen & Gitlin, 2007). A review by (Todorich B et al. 2008. Oligodendrocytes and myelination: The role of iron. Glia https: / / doi.org / 10.1002 / glia.20784) highlights the importance of iron for oligodendrocytes (they are the principal cells in the CNS that stain for iron under normal conditions) and for myelin production - as demonstrated by studies showing that decreased availability of iron in the diet is associated with hypomyelination. The timing of iron delivery to oligodendrocytes during development is also important because hypomyelination and the associated neurological sequelae persist long afterthe systemic iron deficiency has been corrected. Preclinical studies and different animal models showed that disruption of iron availability either by limiting dietary iron or by altering iron storage capacity resulted in a decrease in myelin proteins and lipids (Ortiz et al., 2004; Badaracco et al., 2008) as well as reduced mean density of myelinated fibres during development (DeMaman et al., 2010). Among the integral myelin proteins, proteolipid protein was most consistently affected, suggesting that limiting iron to oligodendrocytes results in hypomyelination and a decrease in myelin compaction.

[0076] The term "choline" as used herein refers to an essential nutrient that is naturally present in some foods and available as a dietary supplement. Choline is a source of methyl groups needed for many steps in metabolism. The body needs choline to synthesize phosphatidylcholine and sphingomyelin, two major phospholipids vital for cell membranes.

[0077] Choline also plays important roles in modulating gene expression, cell membrane signaling, lipid transport and metabolism, and early brain development (Zeisel SH, Corbin KD. Choline. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Washington, DC: Wiley-Blackwell; 2012:405-18).

[0078] Humans can produce choline endogenously in the liver, mostly as phosphatidylcholine, but the amount that the body naturally synthesizes is not sufficient to meet human needs. As a result, humans must obtain some choline from the diet.

[0079] The term "lutein" as used herein refers to a type of organic pigment called a carotenoid. It is related to beta-carotene and vitamin A. Many people think of lutein as "the eye vitamin." Lutein is one of two major carotenoids found in the human eye (macula and retina). It is thought to function as a light filter, protecting the eye tissues from sunlight damage. Foods rich in lutein include egg yolks, spinach, kale, corn, orange pepper, kiwi fruit, grapes, zucchini, and squash (Wilson LM, Tharmarajah S, Jia Y, Semba RD, Schaumberg DA, Robinson KA. The Effect of Lutein / Zeaxanthin Intake on Human Macular Pigment Optical Density: A Systematic Review and Meta-Analysis. Adv Nutr 2021; Leermakers ET, Darweesh SK, Baena CP, et al. The effects of lutein on cardiometabolic health across the life course: a systematic review and meta-analysis. Am J Clin Nutr 2016;103:481-94).

[0080] The term "zeaxanthin" as used herein refers to a non-provitamin A carotenoid that belongs to the xanthophyll family, has been less studied than its isomer lutein. However, zeaxanthin has also been shown to have a number of beneficial effects for human health due to its ability to quench free radicals, exert antioxidant effects, as well as decrease inflammation (Murillo AG, Hu S, Fernandez ML. Zeaxanthin: Metabolism, Properties, and Antioxidant Protection of Eyes, Heart, Liver, and Skin. Antioxidants (Basel). 2019 Sep ll;8(9):390. doi: 10.3390 / antiox8090390. PMID: 31514298; PMCID: PMC6770730).

[0081] As used herein, "about" is understood to refer to numbers in a range of numerals, for example the range of -10% to +10% of the referenced number, within -5% to +5% of the referenced number, or in one aspect, within -1% to +1% of the referenced number, and in a specific aspect, within -0.1% to +0.1% of the referenced number. Furthermore, all numerical ranges herein should be understood to include all integers, whole or fractions, within the range. Moreover, these numerical ranges should be construed as providing support for a claim directed to any number or subset of numbers in that range. For example, a disclosure of from 1 to 10 should be construed as supporting a range of from 1 to 8, from 3 to 7, from 1 to 9, from 3.6 to 4.6, from 3.5 to 9.9, and so forth.

[0082] In the context of the invention, the terms "comprising" or "comprises" do not exclude other possible elements. The composition of the present invention, including the many embodiments described herein, can comprise, consist of, or consist essentially of the essential elements and limitations of the invention described herein, as well as any additional or optional ingredients, components, or limitations described herein or otherwise depending on the needs. All percentages are by weight unless otherwise stated.

[0083] The terms "in particular" or "more particularly" as used herein should not be considered limiting but should be interpreted as being synonymous with "for example" or "especially".

[0084] As used in this disclosure and the appended claims, the singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a component" or "the component" includes two or more components.

[0085] The objective of the present invention is hence to enrich or improve the state of the art and in particular to provide a combination of nutrients for use in improving social-emotional skills and / or promoting mood and joy behaviours in infants, toddlers and young children.

[0086] The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that such publications constitute prior art to the claims appended hereto.

[0087] Embodiments of the invention

[0088] The invention will be now described in further detail. All weights being per dry weight of the composition unless otherwise specified.

[0089] In a first aspect, the present invention refers to a nutritional composition comprising hexadecenoic acid and sphingomyelin, for use in improving cognition and / or learning in a subject.

[0090] In one embodiment, the amount of hexadecenoic acid administered to a subject is greater than or equal to 0.15g per day.

[0091] In one embodiment, the amount of hexadecenoic acid administered to a subject is greater than or equal to 0.3g, greater than or equal to 0.4g, greater than or equal to 0.5g, greater than or equal to 0.8g, greater than or equal to 1.0g, greater than or equal to 1.5g, greater than or equal to 2.0g, greater than or equal to 2.5g, or greater than or equal to 3.0g per day.

[0092] In one embodiment, the amount of hexadecenoic acid administered to a subject is less than or equal to 3.2g per day.

[0093] In one embodiment, the amount of hexadecenoic acid administered to a subject is less than or equal to 3.0g, less than or equal to 2.5g, less than or equal to 2.0g, less than or equal to 1.5g, less than or equal to 1.0g, less than or equal to 0.8g, less than or equal to 0.5g, less than or equal to 0.4g, or less than or equal to 0.3g per day.

[0094] In one embodiment, the amount of hexadecenoic acid administered to a subject is greater than or equal to 0.15g per day and less than or equal to 3.2g per day.

[0095] In one embodiment, the amount of hexadecenoic acid administered to a subject is greater than or equal to 0.3g per day and less than or equal to 3.0g per day, greater than or equal to 0.4g per day and less than or equal to 2.5g per day, greater than or equal to 0.5g per day and less than or equal to 2.0g per day, greater than or equal to 0.5g per day and less than or equal to 1.5g per day, or greater than or equal to 0.5g per day and less than or equal to 1.0g per day.

[0096] Preferably, the amount of hexadecenoic acid administered to a subject is greater than or equal to 0.3g per day and less than or equal to 2.0g per day, more preferably greater than or equal to 0.3g per day and less than or equal to 1.5g per day, or most preferably greater than or equal to 0.3g per day and less than or equal to 0.8g.

[0097] In one embodiment, the nutritional composition comprises hexadecenoic acid in an amount greater than or equal to 0.2g / 100g of the dry weight of the composition, more particularly ranging from 0.2g to 12.5g / 100g of the dry weight of the composition.

[0098] In an embodiment the nutritional composition comprises hexadecenoic acid in an amount selected from the group consisting of; greater than or equal to 0.2g / 100g, greater than or equal to 0.5g / 100g, greater than or equal to lg / lOOg, greater than or equal to 2g / 100g, greater than or equal to 4g / 100g, greater than or equal to 6g / 100g, greater than or equal to 8g / 100g, greater than or equal to lOg / lOOg.

[0099] In an embodiment the nutritional composition comprises hexadecenoic acid in an amount selected from the group consisting of; less than or equal to 12.5g / 100g, less than or equal to lOg / lOOg, less than or equal to 8g / 100g, less than or equal to 6g / 100g, less than or equal to 4g / 100g, less than or equal to 3g / 100g, less than or equal to 2g / 100g, less than or equal to lg / 100g.

[0100] In an embodiment the nutritional composition comprises hexadecenoic acid in an amount selected from the group consisting of; greater than or equal to 0.2g / 100g and less than or equal to 12.5g / 100g, greater than or equal to 0.5g / 100g and less than or equal to lOg / lOOg, greater than or equal to lg / lOOg and less than or equal to lOg / lOOg, greater than or equal to 2g / lOOg and less than or equal to 8g / 100g, greater than or equal to 4g / 100g and less than or equal to 8g / 100g.

[0101] In a preferred embodiment, the nutritional composition comprises hexadecenoic acid in an amount selected from the group consisting of; greater than or equal to 0.2g / 100g and less than or equal to 12.5g / 100g, more preferably greater than or equal to 0.2g / 100g and less than or equal to 6g / 100g, most preferably greater than or equal to 0.2g / 100g and less than or equal to lg / lOOg.

[0102] In one embodiment, the subject is older than 2 years old, older than 3 years old, older than 4 years old, older than 5 years old, older than 6 years old, older than 7 years old, older than 8 years old, older than 9 years old, older than 10 years old, older than 11 years old, older than 12 years old, older than 13 years old, older than 14 years old, older than 15 years old.

[0103] In one embodiment, the subject is between 2 and 15 years old.

[0104] In one embodiment, the subject is between 3 and 15 years old, between 4 and 15 years old, between 5 and 15 years old, between 6 and 15 years old, between 7 and 15 years old, between 8 and 15 years old, between 9 and 15 years old, between 10 and 15 years old, between 11 and 15 years old, between 12 and 15 years old, between 13 and 15 years old, between 14 and 15 years old.

[0105] In a preferred embodiment, the subject is between 3 and 15 years old, more preferably between 4 and 15 years old, most preferably between 5 and 15 years old.

[0106] In one embodiment, the subject is a school aged child.

[0107] In an embodiment, the nutritional composition comprises a combination of hexadecenoic acid and sphingomyelin for use in improving cognition and / or learning in a subject.

[0108] In a further embodiment, the nutritional composition comprises a combination of hexadecenoic acid, sphingomyelin, folate and iron for use in improving cognition in a subject. In a further embodiment, the nutritional composition comprises a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline for use in improving cognition in a subject.

[0109] In a further embodiment, the nutritional composition comprises a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron for use in improving learning in a subject.

[0110] In a further embodiment, the nutritional composition comprises a combination of hexadecenoic acid, sphingomyelin, DHA and choline for use in improving learning in a subject.

[0111] In one embodiment, cognition is selected from verbal comprehension, visual spatial, fluid reasoning, working memory and / or processing speed.

[0112] In a further embodiment, learning is selected from letter / word reading, spelling, reading comprehension and / or mathematical calculation.

[0113] In one embodiment the amount of sphingomyelin in the nutritional composition administered to a subject is greater than or equal to 0.6mg per day.

[0114] In one embodiment, the amount of sphingomyelin administered to a subject is greater than or equal to lmg, greater than or equal to 5mg, greater than or equal to lOmg, greater than or equal to 15mg, greater than or equal to 20mg, greater than or equal to 30mg, greater than or equal to 40mg, greater than or equal to 50mg, greater than or equal to 60mg, or greater than or equal to 70mg per day.

[0115] In one embodiment, the amount of sphingomyelin administered to a subject is less than or equal to 77mg per day.

[0116] In one embodiment, the amount of sphingomyelin administered to a subject is less than or equal to 70mg, less than or equal to 60mg, less than or equal to 50mg, less than or equal to 40mg, less than or equal to 30mg, less than or equal to 20mg, less than or equal to 15mg, less than or equal to lOmg, less than or equal to 5mg, or less than or equal to lmg per day.

[0117] In one embodiment, the amount of sphingomyelin administered to a subject is greater than or equal to 0.6mg per day and less than or equal to 77mg per day. In one embodiment, the amount of sphingomyelin administered to a subject is greater than or equal to lmg per day and less than or equal to 70mg per day, greater than or equal to 5mg per day and less than or equal to 60mg per day, greater than or equal to lOmg per day and less than or equal to 50mg per day, greater than or equal to 15mg per day and less than or equal to 40mg per day, or greater than or equal to 15mg per day and less than or equal to 30mg per day.

[0118] Preferably, the amount of sphingomyelin administered to a subject is greater than or equal to lmg per day and less than or equal to 30mg per day, more preferably greater than or equal to 5mg per day and less than or equal to 25mg per day, or most preferably greater than or equal to lOmg per day and less than or equal to 20mg per day.

[0119] In one embodiment, the nutritional composition comprises sphingomyelin in an amount greater than or equal to 1.9mg / 100g of the dry weight of the composition, more particularly ranging from 1.9mg to 236mg / 100g of the dry weight of the composition.

[0120] In an embodiment the nutritional composition comprises sphingomyelin in an amount selected from the group consisting of; greater than or equal to 5mg / 100g, greater than or equal to lOmg / lOOg, greater than or equal to 25mg / 100g, greater than or equal to 50mg / 100g, greater than or equal to 75mg / 100g, greater than or equal to lOOmg / lOOg, greater than or equal to 15Og / lOOg, greater than or equal to 200mg / 100g.

[0121] In an embodiment the nutritional composition comprises sphingomyelin in an amount selected from the group consisting of; less than or equal to 200mg / 100g, less than or equal to 150mg / 100g, less than or equal to lOOmg / lOOg, less than or equal to 75mg / 100g, less than or equal to 5Og / lOOg, less than or equal to 25g / lOOg, less than or equal to lOmg / lOOg, less than or equal to 5mg / 100g.

[0122] In an embodiment the nutritional composition comprises sphingomyelin in an amount selected from the group consisting of; greater than or equal to 5mg / 100g and less than or equal to 200mg / 100g, greater than or equal to lOmg / lOOg and less than or equal to 200mg / 100g, greater than or equal to 25mg / 100g and less than or equal to 150mg / 100g, greater than or equal to 25mg / 100g and less than or equal to lOOmg / lOOg, greater than or equal to 50mg / 100g and less than or equal to 150mg / 100g. In a preferred embodiment, the nutritional composition comprises sphingomyelin in an amount selected from the group consisting of; greater than or equal to 15mg / 100g and less than or equal to 150mg / 100g, more preferably greater than or equal to 25mg / 100g and less than or equal to lOOg / lOOg, most preferably greater than or equal to 25mg / 100g and less than or equal to 75mg / 100g.

[0123] In one embodiment the amount of folate in the nutritional composition administered to a subject is greater than or equal to 54pg per day.

[0124] In one embodiment, the amount of folate administered to a subject is greater than or equal to lOOpg, greater than or equal to 200pg, greater than or equal to 300pg, greater than or equal to 400pg, greater than or equal to 500pg, greater than or equal to 600pg, greater than or equal to 700pg, greater than or equal to 800pg, greater than or equal to 900pg, or greater than or equal to lOOOpg per day.

[0125] In one embodiment, the amount of folate administered to a subject is less than or equal to llOOpg per day.

[0126] In one embodiment, the amount of folate administered to a subject is less than or equal to lOOOpg, less than or equal to 900pg, less than or equal to 800pg, less than or equal to 700pg, less than or equal to 600pg, less than or equal to 500pg, less than or equal to 400pg, less than or equal to 300pg, less than or equal to 200pg, or less than or equal to lOOpg per day.

[0127] In one embodiment, the amount of folate administered to a subject is greater than or equal to 54pg per day and less than or equal to llOOpg per day.

[0128] In one embodiment, the amount of folate administered to a subject is greater than or equal to lOOpg per day and less than or equal to lOOOpg per day, greater than or equal to 200pg per day and less than or equal to 900pg per day, greater than or equal to 300pg per day and less than or equal to 800pg per day, greater than or equal to 300pg per day and less than or equal to 700pg per day, or greater than or equal to 300pg per day and less than or equal to 600pg per day.

[0129] Preferably, the amount of folate administered to a subject is greater than or equal to 50pg per day and less than or equal to 600pg per day, more preferably greater than or equal to 150pg per day and less than or equal to 500pg per day, or most preferably greater than or equal to 250pg per day and less than or equal to 450pg per day.

[0130] In one embodiment, the nutritional composition comprises folate in an amount greater than or equal to 168pg / 100g of the dry weight of the composition, more particularly ranging from greater than or equal to 168pg to less than or equal to 3400pg / 100g of the dry weight of the composition.

[0131] In an embodiment the nutritional composition comprises folate in an amount selected from the group consisting of; greater than or equal to 200pg / 100g, greater than or equal to 500pg / 100g, greater than or equal to 750pg / 100g, greater than or equal to lOOOpg / lOOg, greater than or equal to 1500pg / 100g, greater than or equal to 2000pg / 100g, greater than or equal to 2500pg / 100g, greater than or equal to 3000pg / 100g.

[0132] In an embodiment the nutritional composition comprises folate in an amount selected from the group consisting of; less than or equal to 3000pg / 100g, less than or equal to 2500pg / 100g, less than or equal to 2000pg / 100g, less than or equal to 1500pg / 100g, less than or equal to lOOOpg / lOOg, less than or equal to 750pg / 100g, less than or equal to 500pg / 100g, less than or equal to 200pg / 100g.

[0133] In an embodiment the nutritional composition comprises folate in an amount selected from the group consisting of; greater than or equal to 200pg / 100g and less than or equal to 2500pg / 100g, greater than or equal to 500pg / 100g and less than or equal to 2000pg / 100g, greater than or equal to 500pg / 100g and less than or equal to 1500pg / 100g, greater than or equal to 750pg / 100g and less than or equal to 1500pg / 100g, greater than or equal to 750pg / 100g and less than or equal to lOOOpg / lOOg.

[0134] In a preferred embodiment, the nutritional composition comprises folate in an amount selected from the group consisting of; greater than or equal to 250pg / 100g and less than or equal to 2000pg / 100g, more preferably greater than or equal to 500pg / 100g and less than or equal to 1500pg / 100g, most preferably greater than or equal to 750pg / 100g and less than or equal to 1250pg / 100g.

[0135] In one embodiment the amount of iron in the nutritional composition administered to a subject is greater than or equal to 0.56mg per day. In one embodiment, the amount of iron administered to a subject is greater than or equal to lmg, greater than or equal to 2mg, greater than or equal to 5mg, greater than or equal to 8mg, greater than or equal to lOmg, greater than or equal to 15mg, greater than or equal to 20mg, greater than or equal to 25mg, greater than or equal to 30mg, or greater than or equal to 45mg per day.

[0136] In one embodiment, the amount of iron administered to a subject is less than or equal to 50mg per day.

[0137] In one embodiment, the amount of iron administered to a subject is less than or equal to 45mg, less than or equal to 30mg, less than or equal to 25mg, less than or equal to 20mg, less than or equal to 15mg, less than or equal to lOmg, less than or equal to 8mg, less than or equal to 5mg, less than or equal to 2mg, or less than or equal to lmg per day.

[0138] In one embodiment, the amount of iron administered to a subject is greater than or equal to 0.5mg per day and less than or equal to 50mg per day.

[0139] In one embodiment, the amount of iron administered to a subject is greater than or equal to lmg per day and less than or equal to 45mg per day, greater than or equal to 2mg per day and less than or equal to 40mg per day, greater than or equal to 5mg per day and less than or equal to 35mg per day, greater than or equal to lOmg per day and less than or equal to 30mg per day, or greater than or equal to 15mg per day and less than or equal to 25mg per day.

[0140] Preferably, the amount of iron administered to a subject is greater than or equal to 2mg per day and less than or equal to 35mg per day, more preferably greater than or equal to 5mg per day and less than or equal to 25mg per day, or most preferably greater than or equal to 5mg per day and less than or equal to 15mg per day.

[0141] In one embodiment, the nutritional composition comprises iron in an amount greater than or equal to 1.7mg / 100g of the dry weight of the composition, more particularly ranging from 1.7mg to 150mg / 100g of the dry weight of the composition.

[0142] In an embodiment the nutritional composition comprises iron in an amount selected from the group consisting of; greater than or equal to 2mg / 100g, greater than or equal to lOmg / lOOg, greater than or equal to 20mg / 100g, greater than or equal to 30mg / 100g, greater than or equal to 50mg / 100g, greater than or equal to 75mg / 100g, greater than or equal to lOOmg / lOOg, greater than or equal to 140mg / 100g.

[0143] In an embodiment the nutritional composition comprises iron in an amount selected from the group consisting of; less than or equal to 140mg / 100g, less than or equal to lOOmg / lOOg, less than or equal to 75mg / 100g, less than or equal to 50mg / 100g, less than or equal to 30mg / 100g, less than or equal to 20mg / 100g, less than or equal to lOmg / lOOg, less than or equal to 2mg / 100g.

[0144] In an embodiment the nutritional composition comprises iron in an amount selected from the group consisting of; greater than or equal to 2mg / 100g and less than or equal to 140mg / 100g, greater than or equal to lOmg / lOOg and less than or equal to lOOmg / lOOg, greater than or equal to 20mg / 100g and less than or equal to 75mg / 100g, greater than or equal to 30mg / 100g and less than or equal to 75mg / 100g, greater than or equal to 30mg / 100g and less than or equal to 50mg / 100g.

[0145] In a preferred embodiment, the nutritional composition comprises iron in an amount selected from the group consisting of; greater than or equal to lOmg / lOOg and less than or equal to lOOmg / lOOg, more preferably greater than or equal to 25mg / 100g and less than or equal to 75mg / 100g, most preferably greater than or equal to 25mg / 100g and less than or equal to 50mg / 100g.

[0146] In one embodiment the amount of lutein and zeaxanthin in the nutritional composition administered to a subject is greater than or equal to 4.5pg per day.

[0147] In one embodiment, the amount of lutein and zeaxanthin administered to a subject is greater than or equal to lOpg, greater than or equal to 50pg, greater than or equal to lOOpg, greater than or equal to 300pg, greater than or equal to 600pg, greater than or equal to 800pg, greater than or equal to lOOOpg, greater than or equal to 2000pg, greater than or equal to 4000pg, or greater than or equal to 5000pg per day.

[0148] In one embodiment, the amount of lutein and zeaxanthin administered to a subject is less than or equal to 5620pg per day.

[0149] In one embodiment, the amount of lutein and zeaxanthin administered to a subject is less than or equal to 5000pg, less than or equal to 4000pg, less than or equal to 2000pg, less than or equal to lOOOpg, less than or equal to 800pg, less than or equal to 600pg, less than or equal to 300pg, less than or equal to lOOpg, less than or equal to 50pg, or less than or equal to lOpg per day.

[0150] In one embodiment, the amount of lutein and zeaxanthin administered to a subject is greater than or equal to 4.5pg per day and less than or equal to 5620pg per day.

[0151] In one embodiment, the amount of lutein and zeaxanthin administered to a subject is greater than or equal to lOpg per day and less than or equal to 5000pg per day, greater than or equal to 50pg per day and less than or equal to 4000pg per day, greater than or equal to lOOpg per day and less than or equal to 2000pg per day, greater than or equal to 300pg per day and less than or equal to lOOOpg per day, or greater than or equal to 600pg per day and less than or equal to 800pg per day.

[0152] Preferably, the amount of lutein and zeaxanthin administered to a subject is greater than or equal to 4.5pg per day and less than or equal to 2000pg per day, more preferably greater than orequal to 200pg per day and less than or equal to lOOOpg per day, or most preferably greater than or equal to 600pg per day and less than or equal to 800pg per day.

[0153] In one embodiment, the nutritional composition comprises lutein and zeaxanthin in an amount greater than or equal to 14pg / 100g of the dry weight of the composition, more particularly ranging from greater than or equal to 14 pg to less than or equal to 17300pg / 100g of the dry weight of the composition.

[0154] In an embodiment the nutritional composition comprises lutein and zeaxanthin in an amount selected from the group consisting of; greater than or equal to lOOpg / lOOg, greater than or equal to 500pg / 100g, greater than or equal to lOOOpg / lOOg, greater than or equal to 1500pg / 100g, greater than or equal to 2000pg / 100g, greater than or equal to 2500pg / 100g, greater than or equal to 5000pg / 100g, greater than or equal to lOOOOpg / lOOg.

[0155] In an embodiment the nutritional composition comprises lutein and zeaxanthin in an amount selected from the group consisting of; less than or equal to 17300pg / 100g, less than or equal to lOOOOpg / lOOg, less than or equal to 5000pg / 100g, less than or equal to 2000pg / 100g, less than or equal to 1500pg / 100g, less than or equal to lOOOpg / lOOg, less than or equal to 500pg / 100g, less than or equal to lOOpg / lOOg. In an embodiment the nutritional composition comprises lutein and zeaxanthin in an amount selected from the group consisting of; greater than or equal to lOOpg / lOOg and less than or equal to 17300pg / 100g, greater than or equal to 500pg / 100g and less than or equal to lOOOOpg / lOOg, greater than or equal to lOOOpg / lOOg and less than or equal to 5OOOpg / lOOg, greater than or equal to 2000pg / 100g and less than or equal to 5000pg / 100g, greater than or equal to 2000pg / 100g and less than or equal to 3500pg / 100g.

[0156] In a preferred embodiment, the nutritional composition comprises lutein and zeaxanthin in an amount selected from the group consisting of; greater than or equal to 500pg / 100g and less than or equal to 5000pg / 100g, more preferably greater than or equal to lOOOpg / lOOg and less than or equal to 3500pg / 100g, most preferably greater than or equal to 1500pg / 100g and less than or equal to 2500pg / 100g.

[0157] In one embodiment the amount of choline in the nutritional composition administered to a subject is greater than or equal to 8.3mg per day.

[0158] In one embodiment, the amount of choline administered to a subject is greater than or equal to 25mg, greaterthan or equal to 75mg, greaterthan or equal to 150mg, greaterthan or equal to 200mg, greater than or equal to 300mg, greater than or equal to 400mg, greater than or equal to 500mg, greater than or equal to 600mg, greater than or equal to 750mg, or greater than or equal to 850mg per day.

[0159] In one embodiment, the amount of choline administered to a subject is less than or equal to 865mg per day.

[0160] In one embodiment, the amount of choline administered to a subject is less than or equal to 850mg, less than or equal to 750mg, less than or equal to 600mg, less than or equal to 500mg, less than or equal to 400mg, less than or equal to 300mg, less than or equal to 200mg, less than or equal to 150mg, less than or equal to 75mg, or less than or equal to 25mg per day.

[0161] In one embodiment, the amount of choline administered to a subject is greater than or equal to 8.3mg per day and less than or equal to 865mg per day.

[0162] In one embodiment, the amount of choline administered to a subject is greater than or equal to 25mg per day and less than or equal to 850mg per day, greater than or equal to 75mg per day and less than or equal to 750mg per day, greater than or equal to 150mg per day and less than or equal to 600mg per day, greater than or equal to 200mg per day and less than or equal to 500mg per day, or greater than or equal to 300mg per day and less than or equal to 400mg per day.

[0163] Preferably, the amount of choline administered to a subject is greater than or equal to 75mg per day and less than or equal to 600mg per day, more preferably greater than or equal to 150mg per day and less than or equal to 500mg per day, or most preferably greater than or equal to 150mg per day and less than or equal to 300mg per day.

[0164] In one embodiment, the nutritional composition comprises choline in an amount greaterthan or equal to 25mg / 100g of the dry weight of the composition, more particularly ranging from 25mg to 2660mg / 100g of the dry weight of the composition.

[0165] In an embodiment the nutritional composition comprises choline in an amount selected from the group consisting of; greater than or equal to lOOmg / lOOg, greater than or equal to 300mg / 100g, greater than or equal to 600mg / 100g, greater than or equal to 750mg / 100g, greater than or equal to lOOOmg / lOOg, greater than or equal to 1500mg / 100g, greater than or equal to 2000mg / 100g, greater than or equal to 2500mg / 100g.

[0166] In an embodiment the nutritional composition comprises choline in an amount selected from the group consisting of; less than or equal to 2500mg / 100g, less than or equal to 2000mg / 100g, less than or equal to 1500mg / 100g, less than or equal to lOOOmg / lOOg, less than or equal to 750mg / 100g, less than or equal to 600mg / 100g, less than or equal to 300mg / 100g, less than or equal to lOOmg / lOOg.

[0167] In an embodiment the nutritional composition comprises choline in an amount selected from the group consisting of; greater than or equal to lOOmg / lOOg and less than or equal to 2500mg / 100g, greater than or equal to 300mg / 100g and less than or equal to 2000mg / 100g, greater than or equal to 600mg / 100g and less than or equal to 1500mg / 100g, greater than or equal to 600mg / 100g and less than or equal to lOOOmg / lOOg, greater than or equal to 600mg / 100g and less than or equal to 800mg / 100g.

[0168] In a preferred embodiment, the nutritional composition comprises choline in an amount selected from the group consisting of; greater than or equal to 25mg / 100g and less than or equal to lOOOmg / lOOg, more preferably greater than or equal to 300mg / 100g and less than or equal to lOOOmg / lOOg, most preferably greater than or equal to 600mg / 100g and less than or equal to 800mg / 100g.

[0169] In one embodiment the amount of vitamin B12 in the nutritional composition administered to a subject is greater than or equal to 0.99pg per day.

[0170] In one embodiment, the amount of vitamin B12 administered to a subject is greater than or equal to 2pg, greater than or equal to 3pg, greater than or equal to 3.5pg, greater than or equal to 5pg, greater than or equal to 8pg, greater than or equal to lOpg, greater than or equal to 12pg, greater than or equal to 14pg, greater than or equal to 16pg, or greater than or equal to 18pg per day.

[0171] In one embodiment, the amount of vitamin B12 administered to a subject is less than or equal to 20pg per day.

[0172] In one embodiment, the amount of vitamin B12 administered to a subject is less than or equal to 18pg, less than or equal to 16pg, less than or equal to 14pg, less than or equal to 12pg, less than or equal to lOpg, less than or equal to 8pg, less than or equal to 5pg, less than or equal to 3.5pg, less than or equal to 3pg, or less than or equal to 2pg per day.

[0173] In one embodiment, the amount of vitamin B12 administered to a subject is greater than or equal to 0.99pg per day and less than or equal to 20pg per day.

[0174] In one embodiment, the amount of vitamin B12 administered to a subject is greater than or equal to 2pg per day and less than or equal to 18pg per day, greater than or equal to 3pg per day and less than or equal to 16pg per day, greater than or equal to 3.5pg per day and less than or equal to 14 pg per day, greater than or equal to 5pg per day and less than or equal to 12pg per day, or greater than or equal to 5pg per day and less than or equal to lOpg per day.

[0175] Preferably, the amount of vitamin B12 administered to a subject is greater than or equal to lpg per day and less than or equal to 12pg per day, more preferably greater than or equal to 2pg per day and less than or equal to 8pg per day, or most preferably greater than or equal to 2pg per day and less than or equal to 6pg per day.

[0176] In one embodiment, the nutritional composition comprises vitamin B12 in an amount greater than or equal to 3pg / 100g of the dry weight of the composition, more particularly ranging from greater than or equal to 3pg to less than or equal to 61pg / 100g of the dry weight of the composition.

[0177] In an embodiment the nutritional composition comprises vitamin B12 in an amount selected from the group consisting of; greater than or equal to 5pg / 100g, greater than or equal to 8pg / 100g, greater than or equal to lOpg / lOOg, greater than or equal to 12pg / 100g, greater than or equal to 20pg / 100g, greater than or equal to 30pg / 100g, greater than or equal to 45pg / 100g, greater than or equal to 55pg / 100g.

[0178] In an embodiment the nutritional composition comprises vitamin B12 in an amount selected from the group consisting of; less than or equal to 55pg / 100g, less than or equal to 45pg / 100g, less than or equal to 30pg / 100g, less than or equal to 20pg / 100g, less than or equal to 12pg / 100g, less than or equal to lOpg / lOOg, less than or equal to 8pg / 100g, less than or equal to 5pg / 100g.

[0179] In an embodiment the nutritional composition comprises vitamin B12 in an amount selected from the group consisting of; greater than or equal to 5pg / 100g and less than or equal to 55pg / 100g, greater than or equal to 8pg / 100g and less than or equal to 45pg / 100g, greater than or equal to lOpg / lOOg and less than or equal to 30pg / 100g, greater than or equal to 12pg / 100g and less than or equal to 30pg / 100g, greater than or equal to 12pg / 100g and less than or equal to 20pg / 100g.

[0180] In a preferred embodiment, the nutritional composition comprises vitamin B12 in an amount selected from the group consisting of; greater than or equal to 3pg / 100g and less than or equal to 30pg / 100g, more preferably greater than or equal to 8pg / 100g and less than or equal to 30pg / 100g, most preferably greater than or equal to 8pg / 100g and less than or equal to 20pg / 100g.

[0181] In one embodiment, the amount of DHA administered to a subject is greater than or equal to 0.05g per day.

[0182] In one embodiment, the amount of DHA administered to a subject is greater than or equal to 0.051g, greaterthan or equal to 0.052g, greaterthan or equal to 0.055g, greaterthan or equal to 0.1g, greater than or equal to 0.2g, greater than or equal to 0.4g, greater than or equal to 0.6g, greater than or equal to 0.8g, or greater than or equal to 1.2g per day. In one embodiment, the amount of DHA administered to a subject is less than or equal to 1.54g per day.

[0183] In one embodiment, the amount of DHA administered to a subject is less than or equal to 1.2g, less than or equal to 0.8g, less than or equal to 0.6g, less than or equal to 0.4g, less than or equal to 0.2g, less than or equal to 0.1g, less than or equal to 0.055g, less than or equal to 0.052g, or less than or equal to 0.051g per day.

[0184] In one embodiment, the amount of DHA administered to a subject is greater than or equal to 0.05g per day and less than or equal to 1.54g per day.

[0185] In one embodiment, the amount of DHA administered to a subject is greater than or equal to 0.051g per day and less than or equal to 1.2g per day, greater than or equal to 0.052g per day and less than or equal to 0.8g per day, greater than or equal to 0.052g per day and less than or equal to 0.6g per day, greater than or equal to 0.055g per day and less than or equal to 0.6g per day, or greater than or equal to 0.1g per day and less than or equal to 0.4g per day.

[0186] Preferably, the amount of DHA administered to a subject is greater than or equal to 0.05g per day and less than or equal to 1.0g per day, more preferably greater than or equal to 0.05g per day and less than or equal to 0.6g per day, or most preferably greater than or equal to 0.05g per day and less than or equal to 0.1g.

[0187] In one embodiment, the nutritional composition comprises DHA in an amount greater than or equal to 0.15g / 100g of the dry weight of the composition, more particularly ranging from 0.15g to 4.75g / 100g of the dry weight of the composition.

[0188] In an embodiment the nutritional composition comprises DHA in an amount selected from the group consisting of; greater than or equal to 0.16g / 100g, greater than or equal to 0.18g / 100g, greater than or equal to 0.2g / 100g, greater than or equal to 0.3g / 100g, greater than or equal to 0.5g / 100g, greater than or equal to l.Og / lOOg, greater than or equal to 2.0g / 100g, greater than or equal to 4.0g / 100g.

[0189] In an embodiment the nutritional composition comprises DHA in an amount selected from the group consisting of; less than or equal to 4.0g / 100g, less than or equal to 2.0g / 100g, less than or equal to l.Og / lOOg, less than or equal to 0.5g / 100g, less than or equal to 0.3g / 100g, less than or equal to 0.2g / 100g, less than or equal to 0.18g / 100g, less than or equal to 0.16g / 100g.

[0190] In an embodiment the nutritional composition comprises DHA in an amount selected from the group consisting of; greater than or equal to 0.16g / 100g and less than or equal to 4.0g / 100g, greater than or equal to 0.16g / 100g and less than or equal to 2.0g / 100g, greater than or equal to 0.18g / 100g and less than or equal to 2.0g / 100g, greater than or equal to 0.18g / 100g and less than or equal to l.Og / lOOg, greater than or equal to 0.3g / 100g and less than or equal to l.Og / lOOg.

[0191] In a preferred embodiment, the nutritional composition comprises DHA in an amount selected from the group consisting of; greater than or equal to 0.15g / 100g and less than or equal to lg / lOOg, more preferably greater than or equal to 0.15g / 100g and less than or equal to 0.8g / 100g, most preferably greater than or equal to 0.15g / 100g and less than or equal to 0.5g / 100g.

[0192] In one embodiment, the nutritional composition is administered after 24 months of life of the subject.

[0193] In a further embodiment, the nutritional composition is administered after 36 months, after 48 months, after 60 months, after 72 months, after 84 months, after 96 months, after 108, or after 120 months, after 132 months or after 144 months of life of the subject.

[0194] In one embodiment, cognition and / or learning are improved in a subject at the age of 2 to 14 years old.

[0195] In a further embodiment, cognition and / or learning are improved in a subject at the age of 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 years old.

[0196] Another embodiment of the present invention relates to a nutritional composition for use in improving cognition and / or learning in a subject, said nutritional composition comprising a combination of hexadecenoic acid and sphingomyelin.

[0197] In an embodiment, the nutritional composition comprises a combination of hexadecenoic acid, sphingomyelin, folate and iron as described above. In a further embodiment, the nutritional composition comprises a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron as described above.

[0198] In a further embodiment, the nutritional composition comprises a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline as described above.

[0199] In a further embodiment, the nutritional composition comprises a combination of hexadecenoic acid, sphingomyelin, DHA and choline as described above.

[0200] In an embodiment, the nutritional composition is a synthetic nutritional composition.

[0201] Suitably, the synthetic nutritional composition may be for example a growing-up milk, a milkbased beverage, a fortifier or a supplement. In one embodiment, the nutritional composition is a milk-based beverage, a fortifier or a supplement that may be intended for between 2 to 15 years of age, more preferably 5 to 15 years of age.

[0202] In another embodiment, the present invention relates to the non-therapeutical use of a combination or nutritional composition as described above for improving cognition and / or learning in a subject, wherein the subject is a school age child aged between 5 to 15 years old.

[0203] In a further embodiment, the present invention relates to a method for improving cognition and / or learning in a subject, said method comprising administering to the subject a combination or a nutritional composition comprising hexadecenoic acid as described above.

[0204] In an embodiment, the method for improving cognition and / or learning in a subject, comprises administering to the subject a combination or a nutritional composition comprising hexadecenoic acid and sphingomyelin as described above.

[0205] In a further embodiment, the method for improving cognition in a subject comprises administering to the subject a combination or a nutritional composition comprising hexadecenoic acid, sphingomyelin, folate and iron as described above.

[0206] In a further embodiment, the method for improving learning in a subject comprises administering to the subject a combination or a nutritional composition comprising hexadecenoic acid, sphingomyelin, vitamin B12 and iron as described above. In a further embodiment, the method for improving cognition in a subject comprises administering to the subject a combination or a nutritional composition comprising hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline as described above.

[0207] In a further embodiment, the method for improving learning in a subject comprises administering to the subject a combination or a nutritional composition comprising hexadecenoic acid, sphingomyelin, DHA and choline as described above.

[0208] In a further embodiment, the present invention describes a nutritional composition for use in improving cognition and / or learning in a subject, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from

[0209] 1.9 mg / lOOg to 236 mg / lOOg, folate in an amount ranging from 168 pg / lOOg to 3400 pg / lOOg and iron in an amount ranging from 1.7 mg / lOOg to 150 mg / lOOg of the dry weight of the composition.

[0210] In a further embodiment, the present invention describes a nutritional composition for use in improving cognition and / or learning in a subject, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from

[0211] 1.9 mg / lOOg to 236 mg / lOOg, lutein and zeaxanthin in an amount ranging from 14 pg / lOOg to 17300 pg / lOOg and choline in an amount ranging from 25 mg / lOOg to 2660 mg / lOOg of the dry weight of the composition.

[0212] In a further embodiment, the present invention describes a nutritional composition for use in improving cognition and / or learning in a subject, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from

[0213] 1.9 mg / lOOg to 236 mg / lOOg, Vitamin B12 in an amount ranging from 3 pg / lOOg to 61 pg / lOOg and iron in an amount ranging from 1.7 mg / lOOg to 150 mg / lOOg of the dry weight of the composition.

[0214] In a further embodiment, the present invention describes a nutritional composition for use in improving cognition and / or learning in a subject, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from

[0215] 1.9 mg / lOOg to 236 mg / lOOg, DHA in an amount ranging from 0.15 g / lOOg to 4.75 g / lOOg and choline in an amount ranging from 25 mg / lOOg to 2660 mg / lOOg of the dry weight of the composition. In an additional embodiment, the present invention describes a nutritional composition for improving cognition in a subject which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, folate in an amount ranging from 168 pg / lOOg to 3400 pg / lOOg and iron in an amount ranging from 1.7 mg / lOOg to 150 mg / lOOg of the dry weight of the composition.

[0216] In an additional embodiment, the present invention describes a nutritional composition for improving cognition in a subject which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, lutein and zeaxanthin in an amount ranging from 14 pg / lOOg to 17300 pg / lOOg and choline in an amount ranging from 25 mg / lOOg to 2660 mg / lOOg of the dry weight of the composition.

[0217] In an additional embodiment, the present invention describes a nutritional composition for improving learning in a subject which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, Vitamin B12 in an amount ranging from 3 pg / lOOg to 61 pg / lOOg and iron in an amount ranging from 1.7 mg / lOOg to 150 mg / lOOg of the dry weight of the composition.

[0218] In an additional embodiment, the present invention describes a nutritional composition for improving learning in a subject which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, DHA in an amount ranging from 0.15 g / lOOg to 4.75 g / lOOg and choline in an amount ranging from 25 mg / lOOg to 2660 mg / lOOg of the dry weight of the composition.

[0219] In a further embodiment, the present invention describes the use of a combination of hexadecenoic acid, sphingomyelin, folate and iron in the manufacture of a nutritional composition for improving cognition in a school age child.

[0220] In a further embodiment, the present invention describes the use of a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline in the manufacture of a nutritional composition for improving cognition in a school age child. In a further embodiment, the present invention describes the use of a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron in the manufacture of a nutritional composition for improving learning in a school age child.

[0221] In a further embodiment, the present invention describes the use of a combination of hexadecenoic acid, sphingomyelin, DHA and choline in the manufacture of a nutritional composition for improving learning in a school age child.

[0222] In a second aspect, the present invention provides a nutritional composition comprising hexadecenoic acid and sphingomyelin.

[0223] In an embodiment, the present invention describes a nutritional composition comprising hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg and sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg.

[0224] In an embodiment, the present invention describes a nutritional composition comprising hexadecenoic acid and sphingomyelin, further comprising folate and iron.

[0225] In an embodiment, the present invention describes a nutritional composition comprising hexadecenoic acid and sphingomyelin, further comprising lutein and zeaxanthin and choline.

[0226] In an embodiment, the present invention describes a nutritional composition comprising hexadecenoic acid and sphingomyelin, further comprising vitamin B12 and iron.

[0227] In an embodiment, the present invention describes a nutritional composition comprising hexadecenoic acid and sphingomyelin, further comprising DHA and choline.

[0228] In an embodiment, the present invention describes a nutritional composition comprising hexadecenoic acid and sphingomyelin, and at least one ingredient selected from the list consisting of: folate, iron, lutein, zeaxanthin, choline, vitamin B12, DHA, iron, and any combination thereof.

[0229] In an embodiment, the present invention describes a nutritional composition comprising hexadecenoic acid and sphingomyelin, and: a. folate, iron; b. lutein, zeaxanthin, choline; c. DHA, choline; or d. vitamin B12, iron ; e. folate, iron, vitamin B12, f. lutein, zeaxanthin, choline, DHA ; g. folate, lutein, zeaxanthin h. lutein, zeaxanthin, vitamin B12 i. Iron, vitamin B12, DHA j. Choline, vitamin B12

[0230] In an embodiment, the present invention describes a nutritional composition for use in improving cognition and / or learning in a subject, comprising hexadecenoic acid and sphingomyelin, further comprising folate and iron.

[0231] In an embodiment, the present invention describes a nutritional composition for use in improving cognition and / or learning in a subject, comprising hexadecenoic acid and sphingomyelin, further comprising lutein and zeaxanthin and choline.

[0232] In an embodiment, the present invention describes a nutritional composition for use in improving cognition and / or learning in a subject, comprising hexadecenoic acid and sphingomyelin, further comprising vitamin B12 and iron.

[0233] In an embodiment, the present invention describes a nutritional composition for use in improving cognition and / or learning in a subject, comprising hexadecenoic acid and sphingomyelin, further comprising DHA and choline.

[0234] In an embodiment, the present invention describes a nutritional composition for use in improving cognition and / or learning in a subject, comprising hexadecenoic acid, sphingomyelin, and at least one ingredient selected from the list consisting of: folate, iron, lutein, zeaxanthin, choline, vitamin B12, DHA, iron, and any combination thereof. In an embodiment, the present invention describes a nutritional composition comprising hexadecenoic acid and sphingomyelin, and: a. folate, iron; b. lutein, zeaxanthin, choline; c. DHA, choline; or d. vitamin B12, iron ; e. folate, iron, vitamin B12, f. lutein, zeaxanthin, choline, DHA ; g. folate, lutein, zeaxanthin h. lutein, zeaxanthin, vitamin B12 i. Iron, vitamin B12, DHA j. Choline, vitamin B12 for use in improving cognition and / or learning in a subject.

[0235] In an embodiment, the present invention describes a nutritional composition, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, folate in an amount ranging from 168 pg / lOOg to 3400 pg / lOOg and iron in an amount ranging from 1.7 mg / lOOg to 150 mg / lOOg of the dry weight of the composition.

[0236] In an embodiment, the present invention describes a nutritional composition, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, lutein and zeaxanthin in an amount ranging from 14 pg / lOOg to 17300 pg / lOOg and choline in an amount ranging from 25 mg / lOOg to 2660 mg / lOOg of the dry weight of the composition.

[0237] In an embodiment, the present invention describes a nutritional composition, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, Vitamin B12 in an amount ranging from 3 pg / lOOg to 61 pg / lOOg and iron in an amount ranging from 1.7 mg / lOOg to 150 mg / lOOg of the dry weight of the composition.

[0238] In an embodiment, the present invention describes a nutritional composition, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, DHA in an amount ranging from 0.15 g / lOOg to 4.75 g / lOOg and choline in an amount ranging from 25 mg / lOOg to 2660 mg / lOOg of the dry weight of the composition.

[0239] In a third aspect, the present invention provides a non-therapeutic method for improving cognition and / or learning in a school age child, the method comprising administering to said child an effective amount of hexadecenoic acid and sphingomyelin.

[0240] In a last aspect, the present invention provides the use of hexadecenoic acid and sphingomyelin, in the manufacture of a nutritional composition for improving cognition and / or learning in a school age child.

[0241] In another embodiment, the present invention relates to a non-therapeutic method for improving cognition and / or learning in a school age child, the method comprising administering to said child an effective amount of hexadecenoic acid and sphingomyelin.

[0242] In an embodiment, the present invention describes a method for improving cognition and / or learning in a subject, the method comprising administering to said subject an effective amount of hexadecenoic acid and sphingomyelin.

[0243] In a further embodiment, the present invention describes a method for improving cognition and / or learning in a school age child, the method comprising administering to said child an effective amount of hexadecenoic acid and sphingomyelin.

[0244] In an embodiment, the present invention describes a method for improving cognition in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, folate and iron.

[0245] In an embodiment, the present invention describes a method for improving cognition in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, folate and iron. In an embodiment, the present invention describes the use of hexadecenoic acid and sphingomyelin, in the manufacture of a nutritional composition for improving cognition and / or learning in a subject.

[0246] In a further embodiment, the present invention describes the use of hexadecenoic acid and sphingomyelin, in the manufacture of a nutritional composition for improving cognition and / or learning in a school age child.

[0247] In an embodiment, the present invention describes the use of a combination of hexadecenoic acid and sphingomyelin and at least one ingredient selected from the list consisting of: folate, iron, lutein, zeaxanthin, choline, vitamin B12, DHA, iron, and any combination thereof, in the manufacture of a nutritional composition for improving cognition and / or learning in a subject.

[0248] In an embodiment, the present invention describes the use of a combination of hexadecenoic acid and sphingomyelin and at least one ingredient selected from the list consisting of: folate, iron, lutein, zeaxanthin, choline, vitamin B12, DHA, iron, and any combination thereof, in the manufacture of a nutritional composition for improving cognition and / or learning in a school age child.

[0249] In an embodiment, the present invention describes the use of a combination of hexadecenoic acid, sphingomyelin, folate and iron in the manufacture of a nutritional composition for improving cognition in a subject.

[0250] In an embodiment, the present invention describes the use of a combination of hexadecenoic acid, sphingomyelin, folate and iron in the manufacture of a nutritional composition for improving cognition in a school age child.

[0251] In an embodiment, the present invention describes a method for improving cognition in a subject, the method comprising administering to said subject an effective amount of a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline.

[0252] In an embodiment, the present invention describes a method for improving cognition in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline.

[0253] In an embodiment, the present invention describes a method for improving cognition in a subject, the method comprising administering to said subject a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline.

[0254] In an embodiment, the present invention describes a method for improving cognition in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline.

[0255] In an embodiment, the present invention describes the use of a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline in the manufacture of a nutritional composition for improving cognition in a subject.

[0256] In an embodiment, the present invention describes the use of a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline in the manufacture of a nutritional composition for improving cognition in a school age child.

[0257] In an embodiment, the present invention describes a method for improving learning in a subject, the method comprising administering to said subject an effective amount of a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron.

[0258] In an embodiment, the present invention describes a method for improving learning in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron.

[0259] In an embodiment, the present invention describes a method for improving learning in a subject, the method comprising administering to said subject a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron.

[0260] In an embodiment, the present invention describes a method for improving learning in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron. In an embodiment, the present invention describes the use of a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron in the manufacture of a nutritional composition for improving learning in a subject. In an embodiment, the present invention describes the use of a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron in the manufacture of a nutritional composition for improving learning in a school age child.

[0261] In an embodiment, the present invention describes a method for improving learning in a subject, the method comprising administering to said subject an effective amount of a combination of hexadecenoic acid, sphingomyelin, DHA and choline.

[0262] In an embodiment, the present invention describes a method for improving learning in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, DHA and choline.

[0263] In an embodiment, the present invention describes a method for improving learning in a subject, the method comprising administering to said subject a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, DHA and choline.

[0264] In an embodiment, the present invention describes a method for improving learning in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, DHA and choline.

[0265] In an embodiment, the present invention describes the use of a combination of hexadecenoic acid, sphingomyelin, DHA and choline in the manufacture of a nutritional composition for improving learning in a subject.

[0266] In an embodiment, the present invention describes the use of a combination of hexadecenoic acid, sphingomyelin, DHA and choline in the manufacture of a nutritional composition for improving learning in a school age child.

[0267] In an embodiment, the present invention describes a non-therapeutic method for improving cognition and / or learning in a school age child, the method comprising administering to said child an effective amount of hexadecenoic acid and sphingomyelin.

[0268] In an embodiment, the present invention describes a non-therapeutic method for improving cognition and / or learning in a subject, the method comprising administering to said subject an effective amount of hexadecenoic acid and sphingomyelin. In an embodiment, the present invention describes a non-therapeutic method for improving cognition and / or learning in a school age child, the method comprising administering to said child an effective amount of hexadecenoic acid and sphingomyelin.

[0269] In an embodiment, the present invention describes a non-therapeutic method for improving cognition in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, folate and iron.

[0270] In an embodiment, the present invention describes a non-therapeutic method for improving cognition in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, folate and iron.

[0271] In an embodiment, the present invention describes a non-therapeutic method for improving cognition in a subject, the method comprising administering to said subject an effective amount of a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline.

[0272] In an embodiment, the present invention describes a non-therapeutic method for improving cognition in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline.

[0273] In an embodiment, the present invention describes a non-therapeutic method for improving cognition in a subject, the method comprising administering to said subject a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline.

[0274] In an embodiment, the present invention describes a non-therapeutic method for improving cognition in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline.

[0275] In an embodiment, the present invention describes a non-therapeutic method for improving learning in a subject, the method comprising administering to said subject an effective amount of a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron. In an embodiment, the present invention describes a non-therapeutic method for improving learning in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron.

[0276] In an embodiment, the present invention describes a non-therapeutic method for improving learning in a subject, the method comprising administering to said subject a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron.

[0277] In an embodiment, the present invention describes a non-therapeutic method for improving learning in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron. Use of a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron in the manufacture of a nutritional composition for improving learning in a subject.

[0278] In an embodiment, the present invention describes a non-therapeutic method for improving learning in a subject, the method comprising administering to said subject an effective amount of a combination of hexadecenoic acid, sphingomyelin, DHA and choline.

[0279] In an embodiment, the present invention describes a non-therapeutic method for improving learning in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, DHA and choline.

[0280] In an embodiment, the present invention describes a non-therapeutic method for improving learning in a subject, the method comprising administering to said subject a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, DHA and choline.

[0281] In an embodiment, the present invention describes a non-therapeutic method for improving learning in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, DHA and choline.

[0282] The methods and uses in improving and / or increasing and / or stimulating and / or promoting cognition and / or learning in a subject according to the present invention are therapeutic or non-therapeutic. In some embodiments the methods and uses in improving and / or increasing and / or stimulating and / or promoting cognition and / or learning in a subject according to the present invention are therapeutic.

[0283] In some embodiments the methods and uses in improving and / or increasing and / or stimulating and / or promoting cognition and / or learning in a subject according to the present invention are non-therapeutic.

[0284] In some embodiments, the invention is defined by the following clauses:

[0285] 1. A nutritional composition comprising hexadecenoic acid and sphingomyelin.

[0286] 2. A nutritional composition according to clause 1, which is a synthetic nutritional composition.

[0287] 3. A nutritional composition according to clause 2, wherein said synthetic nutritional composition is a growing-up milk, a milk-based beverage, a fortifier or a supplement.

[0288] 4. A nutritional composition according to any of the preceding clauses, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg and sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg.

[0289] 5. A nutritional composition according to any of the preceding clauses, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, folate in an amount ranging from 168 pg / lOOg to 3400 pg / lOOg and iron in an amount ranging from 1.7 mg / lOOg to 150 mg / lOOg of the dry weight of the composition.

[0290] 6. A nutritional composition according to any of the preceding clauses, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, lutein and zeaxanthin in an amount ranging from 14 pg / lOOg to 17300 pg / lOOg and choline in an amount ranging from 25 mg / lOOg to 2660 mg / lOOg of the dry weight of the composition.

[0291] 7. A nutritional composition according to any of the preceding clauses, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, Vitamin B12 in an amount ranging from 3 pg / lOOg to 61 pg / lOOg and iron in an amount ranging from 1.7 mg / lOOg to 150 mg / lOOg of the dry weight of the composition. 8. A nutritional composition according to according to any of the preceding clauses, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, DHA in an amount ranging from 0.15 g / lOOg to 4.75 g / lOOg and choline in an amount ranging from 25 mg / lOOg to 2660 mg / lOOg of the dry weight of the composition.

[0292] 9. A nutritional composition according to any of clauses 1 to 4, further comprising folate and iron.

[0293] 10. A nutritional composition according to any of clauses 1 to 4, further comprising lutein and zeaxanthin and choline.

[0294] 11. A nutritional composition according to any of clauses 1 to 4, further comprising vitamin B12 and iron.

[0295] 12. A nutritional composition according to any of clauses 1 to 4, further comprising DHA and choline.

[0296] 13. A nutritional composition according to any of clauses 1 to 4, comprising hexadecenoic acid, sphingomyelin, and at least one ingredient selected from the list consisting of: folate, iron, lutein, zeaxanthin, choline, vitamin B12, DHA, iron, and any combination thereof.

[0297] 14. A nutritional composition according to clause 13, comprising hexadecenoic acid, sphingomyelin, and: a. folate, iron; b. lutein, zeaxanthin, choline; c. DHA, choline; or d. vitamin B12, iron ; e. folate, iron, vitamin B12, f. lutein, zeaxanthin, choline, DHA ; g. folate, lutein, zeaxanthin h. lutein, zeaxanthin, vitamin B12 i. Iron, vitamin B12, DHA j. Choline, vitamin B12

[0298] 15. A nutritional composition according to clause 14, for use in improving cognition and / or learning in a subject. 16. A nutritional composition comprising hexadecenoic acid and sphingomyelin, for use in improving cognition and / or learning in a subject.

[0299] 17. A nutritional composition for use according to clause 16, wherein cognition is selected from verbal comprehension, visual spatial, fluid reasoning, working memory and / or processing speed.

[0300] 18. A nutritional composition for use according clause 16 or clause 17, wherein learning is selected from letter / word reading, spelling, reading comprehension and / or mathematical calculation.

[0301] 19. A nutritional composition for use according to any of clauses 16 to 18, wherein the subject is between 2 and 15 years old.

[0302] 20. A nutritional composition for use according to any of clauses 16 to 19, wherein the subject is a school age child.

[0303] 21. A nutritional composition for use according to any of clauses 16 to 20, wherein said composition is administered after 24 months of life of the subject.

[0304] 22. A nutritional composition for use according to any of clauses 16 to 21 wherein cognition and / or learning are improved in a subject at the age of 2 to 14 years old.

[0305] 23. A nutritional composition for use according to any of clauses 16 to 22 comprising hexadecenoic acid and sphingomyelin.

[0306] 24. A nutritional composition for use according to any of clauses 16 to 23, which is a synthetic nutritional composition.

[0307] 25. A nutritional composition for use according to clauses 24, wherein said synthetic nutritional composition is a growing-up milk, a milk-based beverage, a fortifier or a supplement.

[0308] 26. A nutritional composition for use for use according to any of clauses 16 to 25, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, folate in an amount ranging from 168 pg / lOOg to 3400 pg / lOOg and iron in an amount ranging from 1.7 mg / lOOg to 150 mg / lOOg of the dry weight of the composition.

[0309] 27. A nutritional composition for use for use according to any of clauses 16 to 25, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, lutein and zeaxanthin in an amount ranging from 14 pg / lOOg to 17300 pg / lOOg and choline in an amount ranging from 25 mg / lOOg to 2660 mg / lOOg of the dry weight of the composition.

[0310] 28. A nutritional composition for use for use according to any of clauses 16 to 25, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, Vitamin B12 in an amount ranging from 3 pg / lOOg to 61 pg / lOOg and iron in an amount ranging from 1.7 mg / lOOg to 150 mg / lOOg of the dry weight of the composition.

[0311] 29. A nutritional composition for use for use according to any of clauses 16 to 25, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, DHA in an amount ranging from 0.15 g / lOOg to 4.75 g / lOOg and choline in an amount ranging from 25 mg / lOOg to 2660 mg / lOOg of the dry weight of the composition.

[0312] 30. A nutritional composition for use according to any of clauses 16 to 25, further comprising folate and iron.

[0313] 31. A nutritional composition for use according to any of clauses 16 to 25, further comprising lutein and zeaxanthin and choline.

[0314] 32. A nutritional composition for use according to any of clauses 16 to 25, further comprising vitamin B12 and iron.

[0315] 33. A nutritional composition for use according to any of clauses 16 to 25, further comprising DHA and choline.

[0316] 34. A nutritional composition for use according to any of clauses 16 to 25, comprising hexadecenoic acid, sphingomyelin, and at least one ingredient selected from the list consisting of: folate, iron, lutein, zeaxanthin, choline, vitamin B12, DHA, iron, and any combination thereof.

[0317] 35. A nutritional composition for use according to any of clauses 16 to 25, comprising hexadecenoic acid, sphingomyelin, and: a. folate, iron; b. lutein, zeaxanthin, choline; c. DHA, choline; or d. vitamin B12, iron ; e. folate, iron, vitamin B12, f. lutein, zeaxanthin, choline, DHA ; g. folate, lutein, zeaxanthin h. lutein, zeaxanthin, vitamin B12 i. Iron, vitamin B12, DHA j. choline, vitamin B12

[0318] 36. A method for improving cognition and / or learning in a subject, the method comprising administering to said subject an effective amount of hexadecenoic acid and sphingomyelin.

[0319] 37. A method for improving cognition and / or learning in a school age child, the method comprising administering to said child an effective amount of hexadecenoic acid and sphingomyelin.

[0320] 38. A method for improving cognition in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, folate and iron.

[0321] 39. A method for improving cognition in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, folate and iron.

[0322] 40. Use of hexadecenoic acid and sphingomyelin, in the manufacture of a nutritional composition for improving cognition and / or learning in a subject.

[0323] 41. Use of hexadecenoic acid and sphingomyelin, in the manufacture of a nutritional composition for improving cognition and / or learning in a school age child.

[0324] 42. Use of a combination of hexadecenoic acid and sphingomyelin and at least one ingredient selected from the list consisting of: folate, iron, lutein, zeaxanthin, choline, vitamin B12, DHA, iron, and any combination thereof, in the manufacture of a nutritional composition for improving cognition and / or learning in a subject.

[0325] 43. Use of a combination of hexadecenoic acid and sphingomyelin and at least one ingredient selected from the list consisting of: folate, iron, lutein, zeaxanthin, choline, vitamin B12, DHA, iron, and any combination thereof, in the manufacture of a nutritional composition for improving cognition and / or learning in a school age child.

[0326] 44. Use of a combination of hexadecenoic acid, sphingomyelin, folate and iron in the manufacture of a nutritional composition for improving cognition in a subject.

[0327] 45. Use of a combination of hexadecenoic acid, sphingomyelin, folate and iron in the manufacture of a nutritional composition for improving cognition in a school age child. A method for improving cognition in a subject, the method comprising administering to said subject an effective amount of a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline. A method for improving cognition in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline. A method for improving cognition in a subject, the method comprising administering to said subject a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline. A method for improving cognition in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline. Use of a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline in the manufacture of a nutritional composition for improving cognition in a subject. Use of a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline in the manufacture of a nutritional composition for improving cognition in a school age child. A method for improving learning in a subject, the method comprising administering to said subject an effective amount of a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron. A method for improving learning in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron. A method for improving learning in a subject, the method comprising administering to said subject a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron. A method for improving learning in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron. Use of a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron in the manufacture of a nutritional composition for improving learning in a subject. 56. Use of a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron in the manufacture of a nutritional composition for improving learning in a school age child.

[0328] 57. A method for improving learning in a subject, the method comprising administering to said subject an effective amount of a combination of hexadecenoic acid, sphingomyelin, DHA and choline.

[0329] 58. A method for improving learning in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, DHA and choline.

[0330] 59. A method for improving learning in a subject, the method comprising administering to said subject a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, DHA and choline.

[0331] 60. A method for improving learning in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, DHA and choline.

[0332] 61. Use of a combination of hexadecenoic acid, sphingomyelin, DHA and choline in the manufacture of a nutritional composition for improving learning in a subject.

[0333] 62. Use of a combination of hexadecenoic acid, sphingomyelin, DHA and choline in the manufacture of a nutritional composition for improving learning in a school age child.

[0334] 63. A non-therapeutic method for improving cognition and / or learning in a school age child, the method comprising administering to said child an effective amount of hexadecenoic acid.

[0335] 64. A non-therapeutic method for improving cognition and / or learning in a subject, the method comprising administering to said subject an effective amount of hexadecenoic acid and sphingomyelin.

[0336] 65. A non-therapeutic method for improving cognition and / or learning in a school age child, the method comprising administering to said child an effective amount of hexadecenoic acid and sphingomyelin.

[0337] 66. A non-therapeutic method for improving cognition in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, folate and iron. 67. A non-therapeutic method for improving cognition in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, folate and iron.

[0338] 68. A non-therapeutic method for improving cognition in a subject, the method comprising administering to said subject an effective amount of a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline.

[0339] 69. A non-therapeutic method for improving cognition in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline.

[0340] 70. A non-therapeutic method for improving cognition in a subject, the method comprising administering to said subject a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline.

[0341] 71. A non-therapeutic method for improving cognition in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, lutein and zeaxanthin and choline.

[0342] 72. A non-therapeutic method for improving learning in a subject, the method comprising administering to said subject an effective amount of a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron.

[0343] 73. A non-therapeutic method for improving learning in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron.

[0344] 74. A non-therapeutic method for improving learning in a subject, the method comprising administering to said subject a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron.

[0345] 75. A non-therapeutic method for improving learning in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron. Use of a combination of hexadecenoic acid, sphingomyelin, vitamin B12 and iron in the manufacture of a nutritional composition for improving learning in a subject.

[0346] 76. A non-therapeutic method for improving learning in a subject, the method comprising administering to said subject an effective amount of a combination of hexadecenoic acid, sphingomyelin, DHA and choline. 77. A non-therapeutic method for improving learning in a school age child, the method comprising administering to said child an effective amount of a combination of hexadecenoic acid, sphingomyelin, DHA and choline.

[0347] 78. A non-therapeutic method for improving learning in a subject, the method comprising administering to said subject a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, DHA and choline.

[0348] 79. A non-therapeutic method for improving learning in a school age child, the method comprising administering to said child a nutritional composition which comprises a combination of hexadecenoic acid, sphingomyelin, DHA and choline.

[0349] EXAMPLES

[0350] Material and methods

[0351] The current association study was performed by using a multicentric US-based developmental cohort called ECHO. The Environmental influences on Child Health Outcome Program aims to understand the effects of environmental influences on child development over time. It is a huge observational study that has enrolled more than 50000 children across the US with different races, sex, and backgrounds. In the current study a subsample of children (N =282), mean age 7 y.o., has been selected to investigate the influence of daily nutrition on brain correlates of learning and cognition. Table 1. Illustrates the demographic and neurodevelopmental characteristics of the sample included in the current analysis.

[0352] Specifically, here we performed a series of mediation analyses to investigate the relationship between nutritional intake, brain measures, learning and cognition. Mediation analysis allows to identify and explain the path that underlies an observed relationship between an exposure (nutrition), and an outcome variable (learning or cognition), through the inclusion of an intermediate variable - mediator (myelination and white matter). In this instance we have performed four different mediation analyses, while controlling for covariates such as child's age and maternal education. The following mediation models were included in the analysis:

[0353] 1. Nutrition -> brain myelination -> cognitive skills (WISC / WWPSI)

[0354] 2. Nutrition -> brain myelination -> learning skills (reading)

[0355] 3. Nutrition -> white matter integrity -> cognitive skills 4. Nutrition -> white matter integrity -> learning skills (reading)

[0356] Below is the description of the results of each mediation analysis.

[0357] Table 1. Description of the subsample of the ECHO cohort considered for this analysis. Below illustrated are the demographic (age, sex, ethnicity), developmental (fine and gross motor), cognitive (WISC IQ, WWPSI total), and learning (reading and math) skills.

[0358] Overall

[0359] (N=282) age

[0360] Mean (SD) 7.41 (2.44)

[0361] Median [Min, Max] 7.27 [2.77, 14.3]

[0362] Sex

[0363] Female 115 (40.8%)

[0364] Male 167 (59.2%)

[0365] Ethnicity

[0366] Hispanic / Latino 41 (14.5%)

[0367] Non-Latino / Hispanic 233 (82.6%)

[0368] Unknown 2 (0.7%)

[0369] Missing 6 (2.1%) fine motor skills

[0370] Mean (SD) 54.1 (11.9)

[0371] Median [Min, Max] 54.0 [20.0, 80.0]

[0372] Missing 98 (34.8%) gross motor skills

[0373] Mean (SD) 52.4 (11.2)

[0374] Median [Min, Max] 54.0 [20.0, 80.0] Overall

[0375] (N=282)

[0376] Missing 176 (62.4%)

[0377] Wise IQ

[0378] Mean (SD) 111 (15.5)

[0379] Median [Min, Max] 113 [62.0, 141]

[0380] Missing 52 (18.4%)

[0381] WWPSI total

[0382] Mean (SD) 109 (13.1)

[0383] Median [Min, Max] 111 [69.0, 136]

[0384] Missing 186 (66.0%)

[0385] Reading skills

[0386] Mean (SD) 115 (23.4)

[0387] Median [Min, Max] 118 [50.0, 150]

[0388] Missing 52 (18.4%)

[0389] Math skills

[0390] Mean (SD) 108 (19.0)

[0391] Median [Min, Max] 108 [50.0, 150]

[0392] Missing 51 (18.1%)

[0393] Results

[0394] In the current study the measurement of nutrients consumed on daily basis (64 nutrients, 35 food groups assessed with a food 24 hours recall questionnaire - ASA24) served as the exposure variable, the two brain measures (myelination and white matter diffusion) were the potential mediators, and the scores from the cognitive assessment (WISC / WPPSI) and learning (reading skills) were identified as outcomes. The four mediation analyses described above, were unique parings between exposure, mediator, and outcome. Below are the results described in more detail.

[0395] In the 1stmodel [Nutrition -> brain myelination -> cognitive skills (WISC / WWPSI)], the mediation analysis has identified a "blend" or mix of the following bioactives as the most important nutrients for cognitive skills, mediated by the myelination in the brain: sphingomyelin, hexadecenoic acid (M161 -palmitoleic acid), folate, and iron. Figure 1 illustrates the significant correlations between each bioactive and brain measures. Illustrated in the figure is the overlap between the most significant nutrients (top 10%) associated with myelination across the whole brain. Specifically, the distribution of p-values from highly significant (p=0.001) in light grey to significant (p=0.05) in black. For each significant nutrient (rows) this figure shows the distribution across the brain of significant voxels (or points) associated, along the three brain orientations (saggital, coronal, and axial). In short, this figure shows, where in the brain the myelination is significantly correlated with each of the most important nutrients, linked to cognitive skills.

[0396] In the 2ndmediation model [Nutrition -> brain myelination -> learning (reading skills], the mediation analysis has identified the following nutrients or bioactives that correlated with reading skills, when considering myelination as a mediating factor: sphingomyelin, hexadecenoic acid (M161 -palmitoleic acid), Vitamin B12, and iron. Figure 2 illustrates how each of the significant bioactive is correlated with myelination across the brain. Illustrated in the figure is the overlap between the most significant nutrients (top 10%) associated with myelination across the whole brain. Specifically, the distribution of p-values from highly significant (p=0.001) in light grey to significant (p=0.05) in black. For each significant nutrient (rows) this figure shows the distribution across the brain of significant voxels (or points) associated, along the three brain orientations (saggital, coronal, and axial). In short, this figure shows, where in the brain the myelination is significantly correlated with each of the most important nutrients, linked to learning skills.

[0397] The 3rdmediation model [Nutrition -> white matter integrity -> cognitive skills] where the mediator is the white matter diffusivity, has identified the following bioactives as the most important nutrients influencing cognitive skills, via white matter integrity: sphingomyelin, DHA, hexadecenoic acid (M161 -palmitoleic acid), and choline. Figure 3 illustrates how each nutrient / bioactive is correlated with white matter diffusivity across the brain. Illustrated in the figure is the overlap between the most significant nutrients (top 10%) associated with myelination across the whole brain. Specifically, the distribution of p-values from highly significant (p=0.001) in light grey to significant (p=0.05) in black. For each significant nutrient (rows) this figure shows the distribution across the brain of significant brain areas associated, along the three brain orientations (saggital, coronal, and axial). In short, this figure shows, where in the brain the white matter structural diffusivity (proxy of brain connectivity) is significantly correlated with each of the most important nutrients, linked to cognitive skills.

[0398] The 4thmediation model [Nutrition -> white matter integrity -> learning (reading)] where the mediator variable is the white matter diffusivity has identified the following bioactives as the most influential for reading skills (learning): sphingomyelin, hexadecenoic acid (M161 - palmitoleic acid), lutein and zeaxanthin, and choline. Figure 4 illustrates the distribution of the significant correlations between each nutrient and white matter diffusivity measure across the brain, influencing reading scores. Illustrated in the figure is the overlap between the most significant nutrients (top 10%) associated with myelination across the whole brain. Specifically, the distribution of p-values from highly significant (p=0.001) in light grey to significant (p=0.05) in black. For each significant nutrient (rows) this figure shows the distribution across the brain of significant brain areas associated, along the three brain orientations (saggital, coronal, and axial). In short, this figure shows, where in the brain the white matter structural diffusivity (proxy of brain connectivity) is significantly correlated with each of the most important nutrients, linked to learning (reading) skills.

[0399] Discussion

[0400] In the current study we aimed to assess the regulatory relationship between nutritional intake, myelination / white matter integrity, and learning and cognitive skills in school age children. The results of the mediation analyses introduce a framework with nutritional exposure and high-dimensional cortical mediators, brain myelination and white matter integrity. These two brain measures have been identified as fundamental neural correlates of cognition and learning, especially in school age children. For instance myelination of frontal brain areas has been linked to better cognitive performance, while white matter diffusivity in some brain areas has been linked to reading proficiency (Buyanova et al. (2021) Cerebral White Matter Myelination and Relations to Age, Gender, and Cognition: A Selective Review, Front. Hum. Neurosci. 10.3389 / fnhum.2021.662031). For this reason we have focused on how nutrition can influence cognition and learning, via the most important underlying neural processes (myelination and white matter connectivity). Based on the current data-driven results, we have identified that across the 4 resulting blends the most important nutrients for both myelination and white matter integrity, that have an effect on cognitive and learning skills are: SM, DHA, M161, folate, iron, Vit B12, choline, and lutein and zeaxanthin.

[0401] Table 2. descriptive measures of most important nutrients ranges (min, max, SD), as significant bioactives resulting from all the four mediation analyses. This table illustrated the level of each bioactives' intake at the group level.

[0402] Overall

[0403] (N=282)

[0404] VIT B12 ( ig)

[0405] Mean (SD) 3.93 (2.41)

[0406] Median [Min, Max] 3.68 [0, 19.8]

[0407] Folate total (mcg)

[0408] Mean (SD) 308 (131)

[0409] Median [Min, Max] 279 [0, 1090]

[0410] M161 - Hexadecenoic acid (g)

[0411] Mean (SD) 0.628 (0.395)

[0412] Median [Min, Max] 0.552 [0, 3.10]

[0413] Iron (mg)

[0414] Mean (SD) 10.2 (5.33) Overall

[0415] (N=282)

[0416] Median [Min, Max] 9.61 [0.558, 47.8]

[0417] Choline (mg)

[0418] Mean (SD) 222 (105)

[0419] Median [Min, Max] 212 [8.37, 864]

[0420] DHA (g)

[0421] Mean (SD) 0.0517 (0.108)

[0422] Median [Min, Max] 0.0294 [0, 1.54]

[0423] Sphingomyelin (mg)

[0424] Mean (SD) 15.5 (8.81)

[0425] Median [Min, Max] 14.2 [0.636, 76.6]

[0426] Lutein + Zeaxanthin (pg)

[0427] Mean (SD) 675 (676)

[0428] Median [Min, Max] 521 [4.55, 5620]

[0429] In-vivo study

[0430] Previous studies have shown the correspondence between cognitive function and learning in both children and developing mice (Lang B, Kahnau P, Hohlbaum K, Mieske P, Andresen NP, Boon MN, Thbne-Reineke C, Lewejohann L, Diederich K. Challenges and advanced concepts for the assessment of learning and memory function in mice. Front Behav Neurosci. 2023 Sep 21;17:1230082. doi: 10.3389 / fnbeh.2023.1230082. PMID: 37809039; PMCID: PMC10551171.). Here we have used the Attention Set Shifting Task (ASST) with an Extra Dimensional Shift Task to measure attention, a component of executive functioning, as a proxy of cognition and learning in an animal model. The EDS stage of the ASST in rodents is conceptually analogous to set-shifting components of the Wisconsin Card Sorting Test (WCST) used in humans. This allows to test (i) the inability to re-engage attention towards a previously irrelevant dimension (i.e., "learned irrelevance") and (ii) the inability to release attention from a relevant perception dimension (i.e., perseveration or "stuck-in-set"). Accordingly, during the EDS phase of WCST, individuals are required to redirect their focus toward a dimension of the stimulus that was previously disregarded (e.g., shifting attention from one attribute like colourto another such as shape). Challenges in this phase might reflect both the influence of both learned irrelevance and perseverative tendencies (Fijatkiewicz A, Batko K, Gruszka A. Learned Irrelevance, Perseveration, and Cognitive Aging: A Cross-Sectional Study of Cognitively Unimpaired Older Adults. Brain Sci. 2023 Mar 10;13(3):473. doi: 10.3390 / brainscil3030473. PMID: 36979283; PMCID: PMC10046615.).

[0431] Materials and Methods

[0432] 48 Mice were exposed to a diet containing no sphingomyelin and no omega-7 (hexadecenoic acid) (N=24) or sphingomyelin at a concentration of 7.54 mg / kg / d and omega-7 at a concentration of 0.41g / kg / d (N=24) between post-natal day 21 and 35. At the age of 35 days, mice were habituated, trained and then tested in the ASST as described hereafter.

[0433] Mice were exposed to a progressive food restriction aimed at maintaining 85-90% of their free feeding bodyweight, to ensure motivation to search for a palatable reward. The ASST was conducted in a custom-made opaque PVC U-maze (45 x 30 x 15 cm) with one starting compartment (30 x 30 cm) connected, through a sliding door, to two identical choice compartments (15 x 15 cm). A metal bowl (4.0 cm high, 7.0 cm top diameter, 4.0 cm bottom diameter) was placed in each of the two identical compartments and a small piece of cereal (1 / 4 honey Cheerios®, Nestle, Vevey, Switzerland), covered with 2.0 cm layer of digging medium, was used as a reward. Under the wire-mesh floor of the maze we placed a layer of sawdust bedding from the home-cage of the tested subject to provide a more familiar environment and to reduce the stress due to exposure to a novel environment. Between sessions, the apparatus was cleaned with 30% ethanol / water solution to remove odour cues. The animal went first through a habituation phase, where they were exposed to the apparatus for 5 min 9 times. The following training phase had both bowl baited, and the mice had to retrieve and consume both reward to end the trial, with the trial terminated when the mice went back to its starting box.

[0434] Following these initial phases, the mice entered the testing phase, which consisted of 5 consecutive stages, with increasing difficulty:

[0435] 1. Simple discrimination

[0436] The animal had to discriminate between between two olfactory cues, one leading them to the baited bowl.

[0437] 2. Compound discrimination

[0438] The animal had to discriminate between two olfactory cues, one leading them to the baited bowl, but with difference in the tactile-visual cue (digging material), being irrelevant to obtain the reward.

[0439] 3. Compound discrimination reversal

[0440] The stimuli remained similar to previous stage (compound discrimination), but the relevant stimuli allowing the mice to find the reward was changed to the tactile-visual instead of the olfactory.

[0441] 4. Intra-dimensional shift

[0442] 4 different stimuli (2 olfactory and 2 tactile-visual) were introduced, and the animal had to rely on the olfactory stimuli to find the baited bowl.

[0443] 5. Extra-dimensional shift

[0444] The animal had to rely on the new tactile-visual stimuli introduced in the previous stage to find the reward.

[0445] The animal was given a maximum of 1 minutes or reaching a bowl and searching in it for a reward before the trial was ended. If the animal searched in the wrong bowl or took more than one minute, they were considered as having performed an error. After all trials a lmin timeout was given to the mice. Each mice had to obtain 80% correct choice before being moved to the next stage of the test.

[0446] Performance was measured in number of errors before reaching the 80% successful trial criterion. Results

[0447] In the extra dimensional shift, the mice exposed to the diet with sphingomyelin and omega-7 exhibited a significant (p<0.05) reduction in number of errors before reaching successful criterion (Figure 5). This demonstrates an improvement of various executive function including attention (capacity to focus on the stimuli at disposition), cognitive flexibility (capacity to change the learned strategy) and inhibitory control (capacity to inhibit the previously successful strategy).

[0448] In-vitro study

[0449] The potential of Sphingomyelin (SM) and Hexadecenoic acid (M161) in promoting the maturation and differentiation of oligodendrocyte precursor cells (OPCs) in vitro was further assessed in-vitro. Sphingomyelin, a crucial sphingolipid found in the plasma membrane, plays a significant role in the structural integrity of the myelin sheath that insulates neuronal axons. Its unique amphipathic nature, characterized by a ceramide backbone and a phosphorylcholine head-group, allows it to interact closely with cholesterol, forming liquid- ordered domains that are essential for membrane organization and signaling.

[0450] In this example, the effects of Sphingomyelin and its combination with M161 on the maturation of oligodendrocytes was demonstrated. These are vital for proper neuronal function and cognitive processes. By employing advanced techniques such as Incucyte technology and ELISA, the differentiation states of treated rat OPCs was assessed.

[0451] Materials and Methods

[0452] 1- Cell culture:

[0453] Thawing and establishing Rat OPCs

[0454] OPCs were seeded at a concentration of 340 000 cells / well in a volume of 2000 pl onto the surface of 6-well plates (Falcon - 353224) that had been precoated with Poly -L-Ornithine (SIGMA - P3655). They were cultured in a Complete OPC growth medium: KnockOut™ D- MEM™ / F-12 (GIBCO - 12660-012) supplemented with GlutaMAX™-! (1%, GIBCO - 35050) and StemPro™ NSC SFM™ (2%, GIBCO - A1050801), bFGF (GIBCO - PHG0024), EGF (GIBCO - PHG0314), PDGF-AA (GIBCO - PHG0035) and penicillin / streptomycin solution (0.5%, Sigma - P0781). The plates were incubated at a temperature of 37°C and a 5% CO2in a dedicated incubator. The next day, replace the medium with an equal volume of fresh, pre-warmed complete growth medium. Change the medium every other day, and passage cells when the culture is 80% confluent.

[0455] Expanding rat OPCs

[0456] At 80 % confluence, the cells were harvested and seeded onto the surface of 96-well and 12 well plates at a concentration of 3 x 104 cells / cm2 that had been precoated with Poly-L- Ornithine and laminin (GIBCO - 10267092). The cells were cultured in the same Complete OPC growth medium. The plates were incubated at a temperature of 37°C and a 5% CO2in an incucyte instrument to follow proliferation. Medium was replaced every two days.

[0457] Differentiating rat OPCs

[0458] After 2 days, to spontaneously differentiate Rat OPCs into oligodendrocytes, the medium was changed to complete StemPro™ NSC SFM™ supplemented with 2 mM GlutaMAX™-! and 2% FBS (GIBCO - 10082-147), but without PGDF-AA, bFGF, or EGF, and fresh medium was replaced every other day.

[0459] 2- Experimental conditions:

[0460] Differentiation step

[0461] ■ Treatment and recording

[0462] Two days post- differentiation, the cells were subjected to treatment with either 25uM of Sphingomyelin (Sigma - 860584P), lOOuM of 7(Z)-Hexadecenoic acid (Larodan lipid - 10-1607- 8), a formulation comprising both sphingomyelin and hexadecanoic acid, or caseinate utilized as a vehicle and control. The treated plates were placed in an IncuCyte instrument, where cellular proliferation was monitored at two-hour intervals. The record lasted 66 hours.

[0463] ■ Protein quantification with Elisa At 66 hours after the initiation of treatment, cells were detached using 200 pl of pre-warmed StemPro™ Accutase™ Cell Dissociation Reagent (Sigma - A6964), followed by the addition of 400 pl of medium to halt the dissociation process. The cell suspension was then collected via centrifugation. Subsequently, the cells were washed three times with cold PBS. The washed cells were resuspended in 600 pl of lx PBS and subjected to three freeze-thaw cycles. Following this, the suspension was centrifuged at 1500xg for 10 minutes at 4°C to eliminate cellular debris. The supernatant was carefully transferred to a new tube. The protein content was quantified using the dilution-free RapidGold BCA Protein Assay Kit, utilizing a standard range of 2 mg / ml for BCA. Finally, the ELISA assay (MBP Elisa: AssayGenie - RTDL00655) was performed on the prepared samples.

[0464] Statistical analyses were performed using Prism 8.0 (GraphPad Software, Inc, https: / / www.graphpad.com). A one-way ANOVA was performed followed by Dunnett's post hoc multiple comparison test. Summary data and graphs were presented as mean ± SEM. Significance levels were defined at P < 0.05.

[0465] Results

[0466] To characterize how sphingomyelin and hexadecanoic acid affect myelination, they were tested either individually, or in combination, on primary cell cultures of Oligodrendrocytes. Their impact on maturation and differentiation was then examined.

[0467] 1- Effect of the sphingomyelin alone, hexadecanoic acid alone and the blend of sphingomyelin and hexadecenoic acid together on differentiation

[0468] • IncuCyte

[0469] After a 60-hour treatment period, sphingomyelin, Hexadecenoic acid and the combination of sphingomyelin and Hexadecenoic acid had no effect on the viability of the oligodendrocytes as it was reflected with no change in the viability rate when compared to the control (Figure 6).

[0470] One way Anova F (3, 16) = 0,3802, p =0.7686 Caseinate vs. Sphingomyelin (SM) p= 0,7867

[0471] Caseinate vs. M161_7 p= 0,3180.

[0472] Caseinate vs. SM + M161_7 p= 0,6461.

[0473] • Protein quantification (Elisa)

[0474] In order to quantify the differentiation into mature myelinating cells, the levels of Myelin Basic Protein (MBP) was measured, a known differentiation marker expressed in mature oligodendrocytes. MBP is one of the main protein components of the myelin sheath, accounting for about 30% of the total myelin proteins in the central nervous system (Abubakar Musa Mayaki, Intan Shameha Abdul Razak, Mohd Adzahan Noraniza, Mazlan Mazlina, Abdullah Rasedee. Biofluid Markers of Equine Neurological Disorders Reviewed From Human Perspectives. Journal of Equine Veterinary Science, Volume 86, 2020,).

[0475] After a 60-hour treatment period, sphingomyelin and hexadecanoic acid had no significant effect on the level of MBP, whereas, the combination of sphingomyelin and hexadecanoic resulted in a significant increase in the level of MBP. These results demonstrate a positive effect of the blend on increasing differentiation and thus myelination in vitro.

[0476] One way Anova F (3, 8) = 106,5 p < 0.0001

[0477] Caseinate vs. Sphingomyelin (SM) p= 0,2001

[0478] Caseinate vs. M161_7 p= 0,2359

[0479] Caseinate vs. SM + M161_7 p <0,0001

[0480] This example investigated the effects of sphingomyelin, Hexadecenoic acid and the combination on maturation, and differentiation of oligodendrocytes. The results demonstrate that sphingomyelin, hexadecanoic acid and the blend do not affect the viability of the cells as seen by results provided with the Incucyte. Additionally, protein quantification using ELISA revealed that sphingomyelin and hexadecanoic acid alone did not significantly affect the levels of Myelin Basic Protein (MBP), a marker for mature oligodendrocytes. In contrast, the combination of sphingomyelin and hexadecanoic acid significantly increased MBP levels, suggesting enhanced differentiation and myelination in vitro.

Claims

CLAIMS1. A nutritional composition comprising hexadecenoic acid and sphingomyelin for use in improving cognition and / or learning in a subject.

2. The nutritional composition for use according to claim 1, wherein cognition is verbal comprehension, visual spatial, fluid reasoning, working memory and processing speed.

3. A nutritional composition for use according to any preceding claim, wherein learning is letter / word reading, spelling, reading comprehension and mathematical calculation.

4. A nutritional composition for use according to any preceding claim, wherein the subject is between 2 and 15 years old, preferably a school age child.

5. A nutritional composition for use according to any of claims 1 to 4, further comprising folate and iron.

6. A nutritional composition for use according to any of claims 1 to 4, further comprising lutein and zeaxanthin and choline.

7. A nutritional composition for use according to any of claims 1 to 4, further comprising vitamin B12 and iron.

8. A nutritional composition for use according to any of claims 1 to 4, further comprising DHA and choline.

9. A nutritional composition for use according to claims 1 to 5, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, folate in an amount ranging from 168 pg / lOOg to 3400 pg / lOOg and iron in an amount ranging from 1.7 mg / lOOg to 150 mg / lOOg of the dry weight of the composition.

10. A nutritional composition for use according to claims 1 to 4 and 6, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, lutein and zeaxanthin in an amount ranging from 14 pg / lOOg to 17300 pg / lOOg and choline in an amount ranging from 25 mg / lOOg to 2660 mg / lOOg of the dry weight of the composition.

11. A nutritional composition for use according to claims 1 to 4 and 7, which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, Vitamin B12 in an amount ranging from 3 pg / lOOg to 61 pg / lOOg and iron in an amount ranging from 1.7 mg / lOOg to 150 mg / lOOg of the dry weight of the composition.

12. A nutritional composition for use according to claims 1 to 4, and 8 which comprises hexadecenoic acid in an amount ranging from 0.2 g / lOOg to 12.5 g / lOOg, sphingomyelin in an amount ranging from 1.9 mg / lOOg to 236 mg / lOOg, DHA in an amount ranging from 0.15 g / lOOg to 4.75 g / lOOg and choline in an amount ranging from 25 mg / lOOg to 2660 mg / lOOg of the dry weight of the composition.

13. A nutritional composition for use according to any preceding claim, which is a synthetic nutritional composition.

14. A nutritional composition for use according to claim 13, wherein said synthetic nutritional composition is a growing-up milk, a milk-based beverage, a fortifier or a supplement.

15. A non-therapeutic method for improving cognition and / or learning in a school age child, the method comprising administering to said child an effective amount of hexadecenoic acid and sphingomyelin.

Images