WO2019116329A1 - Use of maltodextrin for enhancing or improving cognition and/or stimulating brain development - Google Patents

Use of maltodextrin for enhancing or improving cognition and/or stimulating brain development Download PDF

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WO2019116329A1
WO2019116329A1 PCT/IB2018/060083 IB2018060083W WO2019116329A1 WO 2019116329 A1 WO2019116329 A1 WO 2019116329A1 IB 2018060083 W IB2018060083 W IB 2018060083W WO 2019116329 A1 WO2019116329 A1 WO 2019116329A1
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maltodextrin
piglets
formula
memory
cognitive
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PCT/IB2018/060083
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French (fr)
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WO2019116329A8 (en
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Cindy LE BOURGOT
Frédérique RESPONDEK
Caroline CLOUARD
Walter GERRITS
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Tereos Starch & Sweeteners Belgium
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/30—Feeding-stuffs specially adapted for particular animals for swines
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/163—Sugars; Polysaccharides
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/60—Feeding-stuffs specially adapted for particular animals for weanlings
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to the field of infant nutrition and the effect of the maltodextrin of the early in life diet on the cognition and brain development later in life.
  • Lactose is the primary carbohydrate in human breast milk and milk-based formulas for infants (Crisa, et al. 2013).
  • lactose-free or reduced- lactose formulas have been increasingly used containing other carbohydrates than lactose (Green Corkins, et al. 2016), mainly driven by the increasing concern surrounding lactose intolerance in infants ⁇ Maldonado, et al. 1998 ⁇ .
  • some authorized glycaemic carbohydrates like maltodextrin, are commonly used in infant and follow-on formulas as alternative sources of carbohydrates (European Union, 2015).
  • maltodextrin as a source of digestible carbohydrates in infant formulas is suggested to help reducing osmotic load and related intestinal distress ⁇ Hofman, et al. 2016 ⁇ , while having no adverse effects on growth ⁇ Heubi, et al. 2000 ⁇ .
  • Maltodextrin is generally considered safe for infant development but its use in infant formulas is often criticized with a lot of misconceptions. It can be suggested to avoid or limit the consumption of maltodextrin because it could be dangerous for infant health and cause malnutrition and health problems. It can be said that the baby will become trained to love super-sweet flavors because parents are often concerned about maltodextrin being added to formula as a sweetener. In addition, little is was known on the impact of a prolonged intake of a maltodextrin-based milk formula replacing lactose-based formula for health and biological functioning later in life, and more particularly on the cognition and brain development.
  • Carbohydrates notably, are the primary source of energy for the development and growth of infants, and glucose, obtained from the digestion and absorption of complex carbohydrates, is the exclusive energy source for perinatal brain development under physiological conditions in humans and animals ⁇ Caravas, et al. 2014; Vannucci, et al. 2000 ⁇ .
  • the patent EP 2 422 629 A 1 refers to a method for enhancing cognition and/or improving the memory of a subject that include administering a nutritional composition including maltodextrin as a carbohydrate source.
  • the nutritional composition is administered such as a single dose of maltodextrin and effects are observed several hours after the intake of the nutritional composition.
  • the patent FR 2 884 422 A1 refers to an intestinal anti-inflammatory composition enriched with fibers characterized in that it comprises branched maltodextrins having a total fiber content of greater than 50% on a dry matter basis.
  • the inventors examine the effects of formulas containing maltodextrin or lactose as the main source of carbohydrates on later life cognitive performance of mammals. Growth and preferences of pigs for sweet caloric or non-caloric solutions have also been assessed to evaluate the potential impact of motivational factors on performance during the holeboard task.
  • the pig an omnivorous species with high cognitive abilities ⁇ Dilger, et al. 2010 ; Gieling, et al. 201 1 ; Kornum, et al. 201 1 ⁇ , shares multiple similarities with humans in terms of nutritional needs, as well as brain development, physiology and function ⁇ Dobbing, et al. 1979; Lind, et al. 2007 ; Roura, et al. 2016 ⁇ , and it is thus an excellent animal model to study the impact of early nutrition on cognitive and behavioural development of human infants ⁇ Clouard, et al. 2012 ; Roura, et al. 2016 ⁇ .
  • the inventors have demonstrated for the first time the beneficial effects of using maltodextrin as the main carbohydrate source in infant formulas compared to lactose on later life cognitive functions of mammals .
  • This invention relates to the use of a digestible maltodextrin having a dextrose equivalent (DE) of between 15 to 19 or a composition comprising thereof in the early childhood of a mammal for enhancing or improving cognition and/or stimulating brain development at adult age of said mammal.
  • DE dextrose equivalent
  • the invention also concerns the use of a maltodextrin or a composition comprising thereof in an infant composition or formula-fed infants or growing up milk for enhancing cognition and/or stimulating brain development at the childhood or adult age of said infant.
  • the present invention demonstrates that replacing lactose with maltodextrin in milk formulas for several weeks during early life induce beneficial effects on cognition by stimulating neurocognitive development compared to standard lactose-based milk formula.
  • the results allow removing prejudices and bring arguments to counter the deleterious effects reported about the infant's consumption of maltodextrins by highlighting positive effects on cognition and brain development.
  • maltodextrin used to replace lactose in milk formula are completely digestible without fiber content, contrary to branched maltodextrins cited in the patent FR 2 884 422 A1 which have a total fiber content of greater than 50% on a dry matter basis.
  • the term "mammal” refers to all animals that belong to the class mammalia. Typically it includes for example, a mouse, rat, bat, dog, cat, rabbit, whale, horse, deer, sheep, goat, buffalo, elk, bear, coyote, mountain lion, raccoon, fox, monkey or human.
  • the animal model chosen is a classically mammal model, the pig which is an omnivorous species with high cognitive abilities ⁇ Dilger, et al. 2010 #24;Gieling, et al. 2011 ;Kornum, et al. 2011 ⁇ , shares multiple similarities with humans in terms of nutritional needs, as well as brain development, physiology and function ⁇ Dobbing, et al. 1979; Lind, et al. 2007; Roura, et al. 2016 ⁇ , and it is thus an excellent animal model to study the impact of early nutrition on cognitive and behavioural development of human infants ⁇ Clouard, et al. 2012; Roura, et al. 2016 ⁇ .
  • The“early childhood” for a mammal refers to the early period of life after birth. In particular for human, it is between 0 to 36 months.
  • infant as used in the present invention are mammals in the early childhood period, for example for human the infant is aged from after birth to 3 years.
  • the terms“childhood” refers to a period after the early childhood to the period before the sexual maturity. In particular for human, it is the period between 3 years to 13 years (before beginning of teenage period).
  • the terms“adult age” or“adult mammal” refers to a mammal which has reached sexual maturity.
  • the terms“improve,”“improving” or“improvement” or grammatical variations thereof used in relation to cognitive functions refer to the ability to achieve a measurable increase in performance in relation to tasks used to test these cognitive functions in mammals.
  • the terms“improving or enhancing cognition at childhood or adult age” and/or“improving memory at childhood or adult age” refers to the measurement of an improvement or an enhancement of cognition or memory at childhood or adult age between two childhood or adult mammals one which has received the nutrition enriched in maltodextrins during early childhood age and the other who has not.
  • maltodextrins are administrated at an early childhood age and notably chronically administrated for example daily or weekly during at least one week to 36 months, preferably 2 weeks to 20 months, typically, 5 weeks to 15 months of the early childhood period.
  • the improvement or enhancement of cognition or memory is observed at the childhood or the adult age, meaning a long time after the end of administration of the maltodextrins.
  • the term “cognition” should be understood as meaning the short-term and / or long-term memory as well as the cognitive flexibility ⁇ Gieling, et al. 2012 ⁇ van der Staay, et al. 2012 ⁇
  • Cognitive flexibility refers to the ability to execute multiple mental tasks simultaneously, to switch from one task to the next easily, and restructure knowledge and strategy to tackle changing tasks. It has been described as the mental ability to control what one is thinking about, how one is thinking about it, and to change one's mind about it. Normal or physiological cognitive flexibility is demonstrated by an animal when it is required to change its thinking about a subject in response to a new set of rules, requiring the animal to perform a previously learned task under a new set of rules sometimes in a new environment.
  • memory is defined as the biological processes of the brain that enable storage and recall of information.
  • memory refers to the short-term memory and the long-term memory.
  • the “holeboard” test provides several scores used to evaluate cognition the working memory scores and the reference memory scores.
  • the Holeboard task consists of finding 4 rewards placed in 4 buckets among 16 proposed buckets with a defined configuration. The trial ended when the individual found all 4 rewards or after 180 sec (maximal timing defined to perform the task).
  • the working memory (WM) score corresponds to the short-term memory and is calculated as the ratio between the number of rewarded visits and the number of visits and revisits to the baited set of buckets.
  • the reference memory (RM) score corresponds to the long term memory and is calculated as the ratio between the number of visits and revisits to the set of baited buckets and the number of visits and revisits to all buckets.
  • the improvement or an enhancement of memory refers more particularly to the improvement of the long-term memory.
  • the long term memory reflects notably the capacity of memorization from one session to another.
  • the improvement or an enhancement of the cognition is the omprovement of enhancement of cognitive flexibility
  • cognitive flexibility reflects the improvement of the adaptation to a new spatial configuration
  • the expression“stimulating brain development” refers to the stimulation of development of the area responsible of spatial cognition and more particularly the hippocampus.
  • the inventors have demonstrated an improvement of RM but not WM due to absorption of maltodextrins in early stage and these parameters reflecting a better spatial long-term memory have been demonstrated to be linked to hippocampus area ( ⁇ Yoon, et al. 2008 ⁇ . ⁇ Pothuizen, et al. 2004 ⁇ Sloan, et al. 2006 ⁇ )
  • effective amount refers to that amount of maltodextrins that will, when administered to the mammal, enhances cognition and/or improves memory of said mammal at a childhood or an adult age and/or stimulates the brain development of said mammal, without any significant adverse side effect, as compared to untreated mammals.
  • effective amounts of maltodextrins for use in the present invention will vary somewhat depending upon the particular species of animal or growth conditions such as temperature and type of feed, and the like. For any particular case, the exact or optimal effective amount to be administered can be determined by conventional dose titration techniques.
  • maltodextrin refers to partially hydrolyzated starch and is digestible. Maltodextrins are defined by the European and US regulation as products having a dextrose equivalent (DE) less than 20. Starch hydrolysates are generally produced by heat, acid, or enzymes. This process breaks down the starch and converts some of the starch to dextrose. With adjustments, this process yields more or less dextrose. Typically the maltodextrins of the invention are digestible maltodextrins. Maltodextrins are therefore classified by dextrose equivalence.
  • Dextrose equivalents are a measure of the reducing sugars present calculated as dextrose and expressed as a percentage of the total dry substance.
  • Maltodextrins can have a dextrose equivalent of up to 20. At above 20 DE, the product is then generally classified as corn syrup solids, which are completely soluble and impart significant sweetness.
  • the maltodextrin of the invention has a DE of between 5 to 20, typically between 10 to 19, more preferably, 15 to 19.
  • Digestible maltodextrin is a low-sweet saccharide polymer consisting of D- glucose units primarily linked linearly with a-1 ,4 bonds; it also has a branched structure through a-1 ,6 bonds. Maltodextrin has an approximate energy value of 4 kcal/g, and is the main carbohydrate source in non-allergenic infant formulas containing non-dairy ingredients ⁇ Hofman, et al., 2016 ⁇
  • the maltodextrins are administrated in the form of nutritional composition or is comprised in a dietary supplement.
  • the invention also concerns the use of a maltodextrin composition which may be a nutritional composition for an early childhood mammals including, but not limited to, a formula-fed infant or a growing up milk but also, dairy product, biscuit, bakery, pastry and bread, sauce, soup, prepared food, frozen food, confectionary, instant product, drinks and shake and chocolate product.
  • a maltodextrin composition which may be a nutritional composition for an early childhood mammals including, but not limited to, a formula-fed infant or a growing up milk but also, dairy product, biscuit, bakery, pastry and bread, sauce, soup, prepared food, frozen food, confectionary, instant product, drinks and shake and chocolate product.
  • said nutritional composition may be comprising:
  • proteins preferably vegetable proteins (i.e. , wheat protein, soy protein, rice protein, potato protein, pea protein, canola protein and mixtures thereof) or animal proteins (i.e., whey protein) and mixtures thereof;
  • fat preferably selected among vegetal oil, animal lipids (i.e. tallow, milk lipids, lard... ) and mix thereof.
  • the protein source may be provided in concentrate form, hydrolysate form, or isolate form, however the hydrolyzed form is particularly preferred.
  • Said animal protein may be selected among milk protein, whey protein, casein protein, and mixtures thereof.
  • Figure 1 The four configurations of baited buckets in the holeboard arena. Piglets were assigned to a fixed configuration during the acquisition phase, and to another configuration during the reversal phase (A to C, B to D, C to A, and D to B).
  • Figure 2. Performance during the acquisition and reversals phases of the spatial holeboard task in piglets fed a lactose-based formula or a maltodextrin-based formula from 1 to 9 weeks of age.
  • Figure 3 Changes of performance between the last block of acquisition trials and the first block of reversal trials in a spatial holeboard task of piglets fed a lactose-based formula or a maltodextrin-based formula from 1 to 9 weeks of age. During the reversal phase, the configuration of rewarded buckets was changed to address cognitive flexibility of the piglets.
  • Figure 4 Intake (kg/kg of BW) of sucralose or sucrose solutions offered during 30- min single-solution tests to piglets fed a lactose-based formula or a maltodextrin- based formula from 1 to 9 weeks of age, and intake (kg/kg of BW) of feed during the 4 hours following the distribution of the solution.
  • Sows and their litter were kept together continuously in the farrowing unit until 2 weeks after the expected farrowing date (15 ⁇ 0.5 days after birth). From 2 to 5 weeks of age, the piglets were subjected to an intermittent suckling (IS) regimen, during which sows were separated from their litter for 8h/day (7:30 to 15:30). During separation, sows were housed individually in a separated room (IS unit) to prevent visual and auditory contact. This procedure allowed to start the dietary intervention at a very young age and stimulate the intake of the formulas, while avoiding stress-related developmental issues that can be caused by a total and early separation from the sow. During lactation, sows were fed twice a day (1 meal in the morning in the IS unit and 1 meal in the afternoon after return to the farrowing unit) a standard commercial diet according to the normal net energy recommendations for lactating sows.
  • IS intermittent suckling
  • piglets were separated from the sows.
  • 8 healthy piglets (4 females and 4 males) with birth weights closest to the average birth weight of the litter were selected from each of the 8 litters and were transported to the experimental farm of Carus (Wageningen University & Research, The Netherlands). Exclusion criteria for selection were very small, sick, lame or weak piglets.
  • the 64 selected piglets were housed in groups of 4 littermates (no mixing), with 2 females and 2 males per pen (280 cm c 180 cm) in 2 identical and adjacent rooms. Pens were equipped with a chain with screws attached to it as enrichment material. Fresh wood shavings were added daily to the pens as bedding.
  • piglets had access to the sow milk only.
  • the lactose-based formula was a commercial formula containing lactose as the main carbohydrate (28% of nutrient composition).
  • the maltodextrin formula consisted in the same formula in which lactose was replaced with maltodextrin (28% of nutrient composition, DE 19).
  • the formulas were obtained by mixing milk powder in lukewarm water, with a milk powder to water ratio of 1 :4. Ingredient and nutrient compositions of the milk powders are indicated in Table 1.
  • Piglets received the formulas from 1 to 9 weeks of age (i.e. 8 to 67 days after birth). Piglets were fed the formulas via milk dispensers, equipped with 1 rescue cup before separation from the sows (1 to 5 weeks of age), and 4 rescue cups mounted in series after separation from the sows (5 to 9 weeks of age). Throughout the entire dietary intervention, formulas were distributed in two meals, at approximately 08:30 and 16:30. Milk dispensers were cleaned daily with hot water, weekly with a basic solution, and monthly with an acidic solution. Allocation of the litters to the formulas were balanced for sow parity, average litter size, and weight at birth. Treatments were distributed in a randomized design within rooms before separation from the sows, and within and between rooms after separation from the sows.
  • piglets From 5 weeks of age onwards (i.e. at separation from the sow), piglets also had restricted access to a commercial creep feed (250 g/pen/day) for 2 h/day to habituate them to solid feed. At 67 days of age, piglets were weaned from milk to a commercial starter diet, over a 3-day transition phase. The starter diet was then offered to the piglets ad libitum until the end of the experiment. Piglets had ad libitum access to water throughout the whole experiment.
  • piglets were weighed individually at birth, at the start of the dietary intervention, at separation from the sows, and at the start and end of holeboard testing, i.e. at 1 , 5, 12 and 17 weeks of age, respectively.
  • piglets were gradually habituated to the experimenters, the buckets and rewards, the corridor leading to the test room, the testing room and the task in sessions of 10-15 min per day for 13 work days.
  • piglets were allowed to explore the holeboard arena, in which the 16 buckets were baited, with their pen mates for 4 days, and individually for 3 days. Piglets were then subjected to individual habituation trials in which only 8 buckets were baited, with at least 2 trials of maximum 3 min per day for 4 days.
  • 2 piglets (1 male and 1 female) were selected per pen based on the responses during the trials. Selection criteria were liking/eating chocolate raisins, showing no extreme stress responses (high-pitch vocalizations, standing alert, escape attempts) when alone in the holeboard arena, and performing the task (i.e. looking in the buckets).
  • piglets were individually subjected to 2 massed trials per day on 14 consecutive work days, i.e. 28 acquisition trials. While a piglet was tested, its pen mates were kept in the waiting area. The trial started when the piglet had its 4 legs in the testing arena and ended when the piglet found all 4 rewards or after 180 sec. Every time the piglet visited a baited bucket for the first time, a clicker sound was produced to facilitate learning. If the piglet completed the task (i.e. found the 4 rewards in less than 180 sec), a bike bell was rang, the exit guillotine door was opened, and the piglet was congratulated (“good job!”,“well done!”), and received a piece of apple.
  • Each piglet was tested on a fixed configuration of baited buckets throughout the acquisition phase, with the configuration of baited buckets differing between the 2 piglets within each pen, and being balanced between formulas and rooms. Testing order within and between pens was alternated within and between days to balance for formulas. Two different entrances were used per day of test (i.e. 1 entrance per trial).
  • the following parameters were scored live using The Observer XT (Noldus Information Technology, Wageningen, The Netherlands): all visits and revisits to all buckets, latencies to all bucket visits, trial duration, total number of defecations, urinations and escape attempts during the trial. From the parameters recorded during the test, the following variables were calculated a posteriori according to ⁇ van der Staay, et al.
  • working memory (WM) score i.e., short-term memory
  • RM reference memory
  • WM working memory
  • RM long-term memory
  • WM errors the number of revisits to baited buckets
  • RM errors the number of visits and revisits to unbaited buckets
  • trial duration is the time needed to complete the task, i.e.
  • piglets were subjected to 2 consecutive single solution consumption tests to assess whether the main source of carbohydrates in early life affects attractiveness for caloric and non-caloric sweet solutions later in life.
  • piglets of half of the pens were given access to a 10% (w/w) sucrose solution, and piglets of the other half of the pens to a 0.125% (w/w) sucralose solution for 30 min/day (10:00-10:30).
  • piglets were offered access to the other solution for another 2-day test; the 2-day tests were separated by the week-end. Order of solution distribution was balanced for treatment and room. On each day of testing, the piglets were deprived from feed for 2.5 hours before starting the test.
  • Performance in the acquisition phase was significantly affected by trial blocks ( Figure 2).
  • WM and RM scores increased linearly, while WM and RM errors, trial duration and total number of visits decreased linearly over trial blocks ( P ⁇ 0.0001 for all).

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Abstract

The invention concerns the use of a maltodextrin or a composition comprising thereof as the main source of carbohydrates in infant nutrition during the early childhood of a mammal for improving or enhancing cognitive performance and/or stimulating brain development.

Description

Use of Maltodextrin for enhancing or improving cognition and/or stimulating brain development
Field of the invention
The present invention relates to the field of infant nutrition and the effect of the maltodextrin of the early in life diet on the cognition and brain development later in life.
Background of the invention
Lactose is the primary carbohydrate in human breast milk and milk-based formulas for infants (Crisa, et al. 2013). In recent years, lactose-free or reduced- lactose formulas have been increasingly used containing other carbohydrates than lactose (Green Corkins, et al. 2016), mainly driven by the increasing concern surrounding lactose intolerance in infants {Maldonado, et al. 1998}. In the European Union, some authorized glycaemic carbohydrates, like maltodextrin, are commonly used in infant and follow-on formulas as alternative sources of carbohydrates (European Union, 2015). The use of maltodextrin as a source of digestible carbohydrates in infant formulas is suggested to help reducing osmotic load and related intestinal distress {Hofman, et al. 2016 }, while having no adverse effects on growth {Heubi, et al. 2000 }.
Maltodextrin is generally considered safe for infant development but its use in infant formulas is often criticized with a lot of misconceptions. It can be suggested to avoid or limit the consumption of maltodextrin because it could be dangerous for infant health and cause malnutrition and health problems. It can be said that the baby will become trained to love super-sweet flavors because parents are often concerned about maltodextrin being added to formula as a sweetener. In addition, little is was known on the impact of a prolonged intake of a maltodextrin-based milk formula replacing lactose-based formula for health and biological functioning later in life, and more particularly on the cognition and brain development. Early nutrition can influence development and may result in long-lasting adaptations of metabolic, immune, behavioural and brain functions in later life, a phenomenon known as nutritional programming {Benton, et al. 2008; Bolton, et al. 2014 ; Langley-Evans, et al. 2009; Moody, et al. 2017; Patel, et al. 2009 }. Carbohydrates, notably, are the primary source of energy for the development and growth of infants, and glucose, obtained from the digestion and absorption of complex carbohydrates, is the exclusive energy source for perinatal brain development under physiological conditions in humans and animals {Caravas, et al. 2014; Vannucci, et al. 2000}. The quality and quantity of carbohydrates consumed in early life have been found to shape offspring’ metabolic profile {Tzanetakou, et al. 201 1 } and food preferences {Stephen, et al. 2012 }. Surprisingly, however, little is known on the relation between early carbohydrate intake and neuro-cognitive development {Stephen, et al. 2012 }. Yet, increased carbohydrate intake in the immediate postnatal life results in behavioural, metabolic, and physical alterations in rats (e.g. hyperphagia, hyperinsulinemia and weight gain){Patel, et al. 2009 }, while intake of carbohydrates with low glycaemic index, measuring the rate at which carbohydrates raise blood glucose levels after ingestion, during pregnancy improves maternal glycaemic control, but also insulin and glucose regulation in the offspring {Tzanetakou, et al. 2011 }. Furthermore, infants fed glucose syrup-containing formulas show different postprandial metabolic responses than infants fed lactose- containing formulas, with, notably, alterations of blood glucose levels {Slupsky, et al. 2017 }. If the source of carbohydrates ingested during a sensitive period of (brain) development can influence (long-term) metabolic functioning of the infant, it is safe to assume that it may also have long-lasting consequences on brain development and cognitive function. No studies have yet investigated the impact of replacing lactose with another source of carbohydrates on later life cognitive functions in formula-fed infants.
The patent EP 2 422 629 A 1 refers to a method for enhancing cognition and/or improving the memory of a subject that include administering a nutritional composition including maltodextrin as a carbohydrate source. The nutritional composition is administered such as a single dose of maltodextrin and effects are observed several hours after the intake of the nutritional composition.
The patent FR 2 884 422 A1 refers to an intestinal anti-inflammatory composition enriched with fibers characterized in that it comprises branched maltodextrins having a total fiber content of greater than 50% on a dry matter basis.
The inventors examine the effects of formulas containing maltodextrin or lactose as the main source of carbohydrates on later life cognitive performance of mammals. Growth and preferences of pigs for sweet caloric or non-caloric solutions have also been assessed to evaluate the potential impact of motivational factors on performance during the holeboard task. The pig, an omnivorous species with high cognitive abilities {Dilger, et al. 2010 ; Gieling, et al. 201 1 ; Kornum, et al. 201 1 }, shares multiple similarities with humans in terms of nutritional needs, as well as brain development, physiology and function {Dobbing, et al. 1979; Lind, et al. 2007 ; Roura, et al. 2016 }, and it is thus an excellent animal model to study the impact of early nutrition on cognitive and behavioural development of human infants {Clouard, et al. 2012 ; Roura, et al. 2016}.
The inventors have demonstrated for the first time the beneficial effects of using maltodextrin as the main carbohydrate source in infant formulas compared to lactose on later life cognitive functions of mammals .
Summary of the invention
This invention relates to the use of a digestible maltodextrin having a dextrose equivalent (DE) of between 15 to 19 or a composition comprising thereof in the early childhood of a mammal for enhancing or improving cognition and/or stimulating brain development at adult age of said mammal. Preferably by administrating to said mammal an effective amount of maltodextrins during the early childhood.
The invention also concerns the use of a maltodextrin or a composition comprising thereof in an infant composition or formula-fed infants or growing up milk for enhancing cognition and/or stimulating brain development at the childhood or adult age of said infant.
The present invention demonstrates that replacing lactose with maltodextrin in milk formulas for several weeks during early life induce beneficial effects on cognition by stimulating neurocognitive development compared to standard lactose-based milk formula. The results allow removing prejudices and bring arguments to counter the deleterious effects reported about the infant's consumption of maltodextrins by highlighting positive effects on cognition and brain development.
In the present invention, maltodextrin used to replace lactose in milk formula are completely digestible without fiber content, contrary to branched maltodextrins cited in the patent FR 2 884 422 A1 which have a total fiber content of greater than 50% on a dry matter basis. As used herein, the term "mammal" refers to all animals that belong to the class mammalia. Typically it includes for example, a mouse, rat, bat, dog, cat, rabbit, whale, horse, deer, sheep, goat, buffalo, elk, bear, coyote, mountain lion, raccoon, fox, monkey or human.
In the study hereunder, the animal model chosen is a classically mammal model, the pig which is an omnivorous species with high cognitive abilities {Dilger, et al. 2010 #24;Gieling, et al. 2011 ;Kornum, et al. 2011}, shares multiple similarities with humans in terms of nutritional needs, as well as brain development, physiology and function {Dobbing, et al. 1979; Lind, et al. 2007; Roura, et al. 2016}, and it is thus an excellent animal model to study the impact of early nutrition on cognitive and behavioural development of human infants {Clouard, et al. 2012; Roura, et al. 2016 }.
The“early childhood” for a mammal refers to the early period of life after birth. In particular for human, it is between 0 to 36 months.
According to the invention, “infant” as used in the present invention are mammals in the early childhood period, for example for human the infant is aged from after birth to 3 years.
According to the invention, the terms“childhood” refers to a period after the early childhood to the period before the sexual maturity. In particular for human, it is the period between 3 years to 13 years (before beginning of teenage period).
According to the invention, the terms“adult age” or“adult mammal” refers to a mammal which has reached sexual maturity.
The terms“improve,”“improving” or“improvement” or grammatical variations thereof used in relation to cognitive functions refer to the ability to achieve a measurable increase in performance in relation to tasks used to test these cognitive functions in mammals.
The terms“improving or enhancing cognition at childhood or adult age” and/or“improving memory at childhood or adult age” refers to the measurement of an improvement or an enhancement of cognition or memory at childhood or adult age between two childhood or adult mammals one which has received the nutrition enriched in maltodextrins during early childhood age and the other who has not. Indeed, according to the invention, although maltodextrins are administrated at an early childhood age and notably chronically administrated for example daily or weekly during at least one week to 36 months, preferably 2 weeks to 20 months, typically, 5 weeks to 15 months of the early childhood period. The improvement or enhancement of cognition or memory is observed at the childhood or the adult age, meaning a long time after the end of administration of the maltodextrins. In the case of pig, the improvement or an enhancement of cognition or memory has been evaluated between 12 and 17 weeks. Consequently, the period between the end of the treatment and the observation of an improvement of improvement or an enhancement of cognition or memory is between 3 and 8 weeks meaning a period which is of about a third or a fourth of the pig lifespan. This effect is called“nutritional programming”. It was very surprising that such nutritional programming effect can be induced by the absorption and notably chronical absorption of maltodextrins.
The improvement or an enhancement of cognition have been evaluated using the“holeboard” test which is well known to assess learning, working and reference memory, as well as cognitive flexibility (i.e. ability to respond to a new spatial configuration, also called‘reversal’) {van der Staay, 2012 }.
According to the invention the term “cognition” should be understood as meaning the short-term and / or long-term memory as well as the cognitive flexibility {Gieling, et al. 2012 }{van der Staay, et al. 2012 }
The terms“Cognitive flexibility” refers to the ability to execute multiple mental tasks simultaneously, to switch from one task to the next easily, and restructure knowledge and strategy to tackle changing tasks. It has been described as the mental ability to control what one is thinking about, how one is thinking about it, and to change one's mind about it. Normal or physiological cognitive flexibility is demonstrated by an animal when it is required to change its thinking about a subject in response to a new set of rules, requiring the animal to perform a previously learned task under a new set of rules sometimes in a new environment.
The term“memory” is defined as the biological processes of the brain that enable storage and recall of information. The term“memory” refers to the short-term memory and the long-term memory.
The “holeboard” test (or Holeboard task) provides several scores used to evaluate cognition the working memory scores and the reference memory scores. The Holeboard task consists of finding 4 rewards placed in 4 buckets among 16 proposed buckets with a defined configuration. The trial ended when the individual found all 4 rewards or after 180 sec (maximal timing defined to perform the task). The working memory (WM) score corresponds to the short-term memory and is calculated as the ratio between the number of rewarded visits and the number of visits and revisits to the baited set of buckets. The reference memory (RM) score corresponds to the long term memory and is calculated as the ratio between the number of visits and revisits to the set of baited buckets and the number of visits and revisits to all buckets.
Typically, the improvement or an enhancement of memory refers more particularly to the improvement of the long-term memory. The long term memory reflects notably the capacity of memorization from one session to another.
Typically, the improvement or an enhancement of the cognition is the omprovement of enhancement of cognitive flexibility cognitive flexibility reflects the improvement of the adaptation to a new spatial configuration.
The expression“stimulating brain development” refers to the stimulation of development of the area responsible of spatial cognition and more particularly the hippocampus. The inventors have demonstrated an improvement of RM but not WM due to absorption of maltodextrins in early stage and these parameters reflecting a better spatial long-term memory have been demonstrated to be linked to hippocampus area ({Yoon, et al. 2008 }. {Pothuizen, et al. 2004 }{Sloan, et al. 2006 })
The term "effective amount" refers to that amount of maltodextrins that will, when administered to the mammal, enhances cognition and/or improves memory of said mammal at a childhood or an adult age and/or stimulates the brain development of said mammal, without any significant adverse side effect, as compared to untreated mammals. As appreciated in the art, effective amounts of maltodextrins for use in the present invention will vary somewhat depending upon the particular species of animal or growth conditions such as temperature and type of feed, and the like. For any particular case, the exact or optimal effective amount to be administered can be determined by conventional dose titration techniques.
As used herein, the term "maltodextrin" refers to partially hydrolyzated starch and is digestible. Maltodextrins are defined by the European and US regulation as products having a dextrose equivalent (DE) less than 20. Starch hydrolysates are generally produced by heat, acid, or enzymes. This process breaks down the starch and converts some of the starch to dextrose. With adjustments, this process yields more or less dextrose. Typically the maltodextrins of the invention are digestible maltodextrins. Maltodextrins are therefore classified by dextrose equivalence. Dextrose equivalents are a measure of the reducing sugars present calculated as dextrose and expressed as a percentage of the total dry substance. Maltodextrins can have a dextrose equivalent of up to 20. At above 20 DE, the product is then generally classified as corn syrup solids, which are completely soluble and impart significant sweetness. Typically the maltodextrin of the invention has a DE of between 5 to 20, typically between 10 to 19, more preferably, 15 to 19.
Digestible maltodextrin is a low-sweet saccharide polymer consisting of D- glucose units primarily linked linearly with a-1 ,4 bonds; it also has a branched structure through a-1 ,6 bonds. Maltodextrin has an approximate energy value of 4 kcal/g, and is the main carbohydrate source in non-allergenic infant formulas containing non-dairy ingredients {Hofman, et al., 2016 }
Preferably, the maltodextrins are administrated in the form of nutritional composition or is comprised in a dietary supplement.
The invention also concerns the use of a maltodextrin composition which may be a nutritional composition for an early childhood mammals including, but not limited to, a formula-fed infant or a growing up milk but also, dairy product, biscuit, bakery, pastry and bread, sauce, soup, prepared food, frozen food, confectionary, instant product, drinks and shake and chocolate product.
Typically said nutritional composition may be comprising:
20 to 30%, preferably 22 to 28 % of proteins preferably vegetable proteins (i.e. , wheat protein, soy protein, rice protein, potato protein, pea protein, canola protein and mixtures thereof) or animal proteins (i.e., whey protein) and mixtures thereof;
20 to 40%, preferably, 25% to 35% of maltodextrin
20 to 40%, preferably 25 to 35% of fat, preferably selected among vegetal oil, animal lipids (i.e. tallow, milk lipids, lard... ) and mix thereof.
The protein source may be provided in concentrate form, hydrolysate form, or isolate form, however the hydrolyzed form is particularly preferred.
Said animal protein may be selected among milk protein, whey protein, casein protein, and mixtures thereof.
The present invention will be further illustrated by the additional description and drawings which follow, which refer to examples illustrating
It should be understood however that these examples are given only by way of illustration of the invention and do not constitute in anyway a limitation thereof. BRIEF DESCRIPTION OF THE FIGURES
Figure 1. The four configurations of baited buckets in the holeboard arena. Piglets were assigned to a fixed configuration during the acquisition phase, and to another configuration during the reversal phase (A to C, B to D, C to A, and D to B). Figure 2. Performance during the acquisition and reversals phases of the spatial holeboard task in piglets fed a lactose-based formula or a maltodextrin-based formula from 1 to 9 weeks of age.
Figure 3. Changes of performance between the last block of acquisition trials and the first block of reversal trials in a spatial holeboard task of piglets fed a lactose-based formula or a maltodextrin-based formula from 1 to 9 weeks of age. During the reversal phase, the configuration of rewarded buckets was changed to address cognitive flexibility of the piglets.
Figure 4. Intake (kg/kg of BW) of sucralose or sucrose solutions offered during 30- min single-solution tests to piglets fed a lactose-based formula or a maltodextrin- based formula from 1 to 9 weeks of age, and intake (kg/kg of BW) of feed during the 4 hours following the distribution of the solution.
Detailed description of the invention EXAMPLE
METHODS
The Animal Welfare Body of Wageningen University & Research has approved this experiment.
Animals and housing A total of 8 multiparous sows (Topigs 20) and their litters (Tempo c Topigs 20) from the Swine Innovation Centre of Wageningen University & Research (VIC, Sterksel, The Netherlands) were used. Lactating sows and their litters were housed in individual farrowing pens (240 cm c 180 cm) equipped with a farrowing crate. A jute bag was provided around parturition to be used as nesting material. Rooms had a natural light- dark cycle. Ambient temperature at arrival of the sows to the farrowing unit, one week before the expected farrowing date, was 25°C and was decreased over lactation via a floor cooling system. From birth onwards, piglets had access to a heated area. Within 24 to 48 hours after birth, if needed, piglets were cross-fostered between sows to balance litter sizes based on the number of functional teats.
Sows and their litter were kept together continuously in the farrowing unit until 2 weeks after the expected farrowing date (15 ± 0.5 days after birth). From 2 to 5 weeks of age, the piglets were subjected to an intermittent suckling (IS) regimen, during which sows were separated from their litter for 8h/day (7:30 to 15:30). During separation, sows were housed individually in a separated room (IS unit) to prevent visual and auditory contact. This procedure allowed to start the dietary intervention at a very young age and stimulate the intake of the formulas, while avoiding stress-related developmental issues that can be caused by a total and early separation from the sow. During lactation, sows were fed twice a day (1 meal in the morning in the IS unit and 1 meal in the afternoon after return to the farrowing unit) a standard commercial diet according to the normal net energy recommendations for lactating sows.
At about 5 weeks of age (36 ± 0.5 days after birth), piglets were separated from the sows. At separation from the sows, 8 healthy piglets (4 females and 4 males) with birth weights closest to the average birth weight of the litter were selected from each of the 8 litters and were transported to the experimental farm of Carus (Wageningen University & Research, The Netherlands). Exclusion criteria for selection were very small, sick, lame or weak piglets. The 64 selected piglets were housed in groups of 4 littermates (no mixing), with 2 females and 2 males per pen (280 cm c 180 cm) in 2 identical and adjacent rooms. Pens were equipped with a chain with screws attached to it as enrichment material. Fresh wood shavings were added daily to the pens as bedding. Fresh straw was added daily to the pens from the end of the dietary intervention onwards, at about 9-10 weeks of age (67 ± 0.5 days after birth). Room temperature at arrival of the piglets was 25°C and was then gradually decreased and kept at 21 °C until the end of the experiment. Lights were on and a radio was playing in the background from 7:00 to 19:00 daily. Formulas and diets
For the first week of life, piglets had access to the sow milk only. At 1 week of age, litters of piglets (n = 4 litters/treatment) were allocated to 1 of 2 formulas differing in their main carbohydrate source. The lactose-based formula was a commercial formula containing lactose as the main carbohydrate (28% of nutrient composition). The maltodextrin formula consisted in the same formula in which lactose was replaced with maltodextrin (28% of nutrient composition, DE 19). The formulas were obtained by mixing milk powder in lukewarm water, with a milk powder to water ratio of 1 :4. Ingredient and nutrient compositions of the milk powders are indicated in Table 1.
Table 1. Ingredient and nutrient compositions of the experimental milk powders
Figure imgf000012_0001
Piglets received the formulas from 1 to 9 weeks of age (i.e. 8 to 67 days after birth). Piglets were fed the formulas via milk dispensers, equipped with 1 rescue cup before separation from the sows (1 to 5 weeks of age), and 4 rescue cups mounted in series after separation from the sows (5 to 9 weeks of age). Throughout the entire dietary intervention, formulas were distributed in two meals, at approximately 08:30 and 16:30. Milk dispensers were cleaned daily with hot water, weekly with a basic solution, and monthly with an acidic solution. Allocation of the litters to the formulas were balanced for sow parity, average litter size, and weight at birth. Treatments were distributed in a randomized design within rooms before separation from the sows, and within and between rooms after separation from the sows.
From 5 weeks of age onwards (i.e. at separation from the sow), piglets also had restricted access to a commercial creep feed (250 g/pen/day) for 2 h/day to habituate them to solid feed. At 67 days of age, piglets were weaned from milk to a commercial starter diet, over a 3-day transition phase. The starter diet was then offered to the piglets ad libitum until the end of the experiment. Piglets had ad libitum access to water throughout the whole experiment.
Measurements
To assess the effect of formulas on piglet growth, piglets were weighed individually at birth, at the start of the dietary intervention, at separation from the sows, and at the start and end of holeboard testing, i.e. at 1 , 5, 12 and 17 weeks of age, respectively.
Spatial cognitive holeboard task
From 12 to 17 weeks of age (i.e. 3 to 8 weeks after the end of the dietary intervention), 2 piglets (1 male and 1 female) per pen (n = 8 pens/treatment) were individually tested in a spatial holeboard task to assess learning, working and reference memory, as well as cognitive flexibility (i.e. ability to respond to a new spatial configuration, also called ‘reversal’) {van der Staay, et al. 2012 }. The test arena (5.3 m c 5.3 m) had black, wooden, 80-cm high walls and 4 entrances with guillotine doors. The arena was surrounded by a corridor, and a waiting area containing a jute bag and some toys that were changed daily. In the arena, 16 grey metallic buckets (diameter: 19 cm) were screwed to the floor in a 4 c 4 matrix (Figure 1). During the test, 4 of the buckets were baited with a chocolate raisin. To prevent the use of visual cues to find the rewards, the chocolate raisins were hidden under a thin layer of grinded straw. All buckets also had a perforated false bottom under which fresh chocolate raisins were placed at the start of the day to prevent the use of odor cues to locate the baited buckets. Piglets were deprived from feed overnight during the 3 phases of holeboard testing (habituation, acquisition and reversal).
Before the start of the test, piglets were gradually habituated to the experimenters, the buckets and rewards, the corridor leading to the test room, the testing room and the task in sessions of 10-15 min per day for 13 work days. After 2 days of habituation to the experimenters, buckets and food rewards in the home pens, piglets were allowed to explore the holeboard arena, in which the 16 buckets were baited, with their pen mates for 4 days, and individually for 3 days. Piglets were then subjected to individual habituation trials in which only 8 buckets were baited, with at least 2 trials of maximum 3 min per day for 4 days. At the end of the 13-day habituation phase, 2 piglets (1 male and 1 female) were selected per pen based on the responses during the trials. Selection criteria were liking/eating chocolate raisins, showing no extreme stress responses (high-pitch vocalizations, standing alert, escape attempts) when alone in the holeboard arena, and performing the task (i.e. looking in the buckets).
After the habituation phase, piglets were individually subjected to 2 massed trials per day on 14 consecutive work days, i.e. 28 acquisition trials. While a piglet was tested, its pen mates were kept in the waiting area. The trial started when the piglet had its 4 legs in the testing arena and ended when the piglet found all 4 rewards or after 180 sec. Every time the piglet visited a baited bucket for the first time, a clicker sound was produced to facilitate learning. If the piglet completed the task (i.e. found the 4 rewards in less than 180 sec), a bike bell was rang, the exit guillotine door was opened, and the piglet was congratulated (“good job!”,“well done!”), and received a piece of apple. If the piglet did not complete the task within the 180 sec, a police siren sound was produced (distinctively different from the bike bell sound); the piglet was not congratulated and did not receive a piece of apple. After each trial, the piglet was led back into the waiting area with its pen mates. After 2 piglets per pen have been tested twice, all the pen mates were led back into their home pen and their feeder was opened. After each trial, feces were removed and urine was wiped from the testing arena. In total 4 different configurations of baited buckets were used (Figure 1). Each piglet was tested on a fixed configuration of baited buckets throughout the acquisition phase, with the configuration of baited buckets differing between the 2 piglets within each pen, and being balanced between formulas and rooms. Testing order within and between pens was alternated within and between days to balance for formulas. Two different entrances were used per day of test (i.e. 1 entrance per trial).
After the acquisition phase was completed, piglets were tested in a reversal phase, with 16 reversal trials in 8 working days. The procedure was the same procedure as that of the acquisition phase, but piglets were assigned to a different configuration of baited buckets (Figure 1).
The following parameters were scored live using The Observer XT (Noldus Information Technology, Wageningen, The Netherlands): all visits and revisits to all buckets, latencies to all bucket visits, trial duration, total number of defecations, urinations and escape attempts during the trial. From the parameters recorded during the test, the following variables were calculated a posteriori according to {van der Staay, et al. 2012 }: working memory (WM) score (i.e., short-term memory) is the ratio between the number of rewarded visits and the number of visits and revisits to the baited set of buckets; reference memory (RM) score (i.e., long-term memory) is the ratio between the number of visits and revisits to the set of baited buckets and the number of visits and revisits to all buckets; WM errors is the number of revisits to baited buckets; RM errors is the number of visits and revisits to unbaited buckets; trial duration is the time needed to complete the task, i.e. latency to fourth baited bucket or 180 sec; inter-visit interval (I VI) is calculated as (time to last bucket visit - latency to first bucket visit) / (number of bucket visits - 1); total number of visits and revisits. Furthermore, difference in performance between the last block of the acquisition phase (block 7) and the first block of the reversal phase (block 8), i.e. transition phase, was assessed and represents a measure of cognitive flexibility after the switch of configuration {Antonides, et al. 2015; Antonides, et al. 2015 }.
Single-solution consumption test
Between 17 and 18 week of age, piglets were subjected to 2 consecutive single solution consumption tests to assess whether the main source of carbohydrates in early life affects attractiveness for caloric and non-caloric sweet solutions later in life. On 2 consecutive days, piglets of half of the pens were given access to a 10% (w/w) sucrose solution, and piglets of the other half of the pens to a 0.125% (w/w) sucralose solution for 30 min/day (10:00-10:30). After the first 2-day test, piglets were offered access to the other solution for another 2-day test; the 2-day tests were separated by the week-end. Order of solution distribution was balanced for treatment and room. On each day of testing, the piglets were deprived from feed for 2.5 hours before starting the test. The solutions were distributed in the milk dispensers used previously. In each pen, the feeder was opened again as soon as the dispenser was filled with the solution. If needed, the dispensers were refilled during the tests so that dispensers were never empty during the 30-min tests. Solution refusals were weighed at the end of the 30-min tests and the dispensers were cleaned with hot water. Feed consumption was measured 4 hours after the feeders were opened (14:00). Solution and feed intake per pen were expressed in kg per kg of body weight.
Statistical analysis
Data were analyzed with SAS version 9.1.3 (Statistical Analysis Software; SAS Institute, Cary, NC, USA). Model residuals were checked for normal distribution using the Shapiro-Wilk test. If model residuals were not normally distributed, data were transformed for analyses. Data are presented as (untransformed) means ± SEMs.
Growth (i.e. average daily gain, ADG, g/d) before and after separation from the sow were analyzed using a MIXED procedure with formula (maltodextrin, control) as fixed effect and pen nested within formulas as random effect. Litter size at birth, included as a covariate in the initial model for ADG before separation from the sow, had no effect on any variables and was removed from the final model. Weight at separation from the sow was included as a covariate in the model for ADG after separation from the sow.
In total, 7 piglets were excluded from the analyses of the holeboard data because they showed extreme stress responses (1 maltodextrin piglet), refused to eat chocolate raisins even when offered by hand (1 pen of 2 maltodextrin piglets, 2 lactose piglets), have had extreme diarrhea at the start of the acquisition, thus not performing the task (1 lactose piglet), or died during the period of test (1 maltodextrin piglet). Means of 4 consecutive trials were calculated, resulting in 7 and 4 trial blocks for acquisition and reversal phases, respectively. Data of the acquisition and reversal phases were analyzed using a MIXED procedure with formulas as fixed effect, block of trials as linear effect, and pen nested within formulas as random effect. Furthermore, the difference in performance during the transition phase was assessed using a MIXED procedure with formula, block and their interaction as fixed effect, and pen nested within formula as random effect. Sex, included as a fixed effect in the initial models, and its interaction with formula, had no effect on any variables and was removed from the final models.
Data from the single-solution consumption tests (solution and feed intake) were expressed in kg per kg of body weight. Data were analyzed using a MIXED procedure with formula (maltodextrin, lactose), solution (sucrose, sucralose), order of presentation (sucrose first, sucralose first) as fixed effects, weight at 17 weeks (before the start of the tests) as covariate, and pen nested with formula as random effect.
RESULTS
Spatial holeboard task Acquisition trials
Performance in the acquisition phase was significantly affected by trial blocks (Figure 2). WM and RM scores increased linearly, while WM and RM errors, trial duration and total number of visits decreased linearly over trial blocks ( P < 0.0001 for all). RM scores were significantly affected by formula c block interactions ( P = 0.0003), with piglets fed the maltodextrin-based formula having better RM scores than lactose group towards the end of the acquisition phase (blocks 5, 6 and 7). Formula had no effect on the other variables during the acquisition phase (P > 0.10 for all).
Transition phase
Piglets had lower RM scores ( P < 0.0001) and made more RM errors (P < 0.0001) during the first block of reversal trials than during the last block of acquisition trials (transition phase; Figure 3). WM scores and errors, however, remained unchanged (P > 0.10). Trial duration (P = 0.006) and latency to first baited visits (P = 0.0005) were significantly longer, and more visits were made (P < 0.0001) during the first block of reversal trials than during the last block of acquisition trials. During this transition phase, piglets fed the maltodextrin-based formula tended to have better RM scores (P = 0.07), and to make fewer RM errors than lactose group ( P = 0.08). No effects of the formula c block interaction were found on any variables.
Reversal trials
After the drop in RM performance after the switch of configuration, RM scores (P < 0.0001) increased linearly, while the number of RM errors (P = 0.0005) decreased linearly over trial blocks during the reversal phase (Figure 2). The WM scores and WM errors were not affected by trial blocks (P > 0.10). Trial duration (P = 0.003), IVI (P = 0.01), total visits (P = 0.003), and latency to first baited visit (P = 0.04) decreased linearly over trial blocks during reversal phase. Formula or its interaction with blocks of trials had no effects on any of the variables during the reversal phase (P > 0.10 for all).
Single-solution consumption test
Irrespective of the formula, piglets drank more sucrose solution than sucralose solution during the test (P = 0.0002; Figure 4). Piglets consumed significantly less feed after the test with the (caloric) sucrose solution than after the test with the (non caloric) sucralose solution (P < 0.0001). The reduced feed intake of pigs tested with the sucrose solution resulted in relatively similar total energy intake (from solution and feed) between pigs tested with the sucrose solution and pigs tested with the sucralose solution (135 vs. 116 kcal/kg of BW). Formula and its interaction with solution had no effect on solution intake during the test (P > 0.10 for both), or feed intake after the test (P > 0.10 for both).
The results clearly indicates that consuming a maltodextrin-based formula, vs. a lactose-based formula, from 1 to 9 weeks of age, improves long-term memory (i.e. reference memory) in a spatial holeboard task, even weeks after the end of the intervention. Growth of the piglets all along the experiment was not affected by the type of carbohydrates contained in the milk formulas.
During the acquisition phase of the holeboard task, RM and WM scores improved, while errors, latency to first reward, and trial duration decreased linearly over time, indicating that young piglets were able to learn the task, as previously reported {Antonides, et al. 2015;Antonides, et al. 2015;Clouard, et al. 2016;Gieling, et al. 2011 }. Piglets fed the maltodextrin-based formula showed, during acquisition, higher RM scores than piglets fed the lactose-based formula. Piglets fed the maltodextrin-based formula also tended to show higher RM scores and made fewer RM errors than the lactose group during the transition phase, i.e. during the switch to a ‘reversed’ configuration of baited buckets. The levels of performance found in both groups are within the ranges of performance reported in prior research using pigs of the same age {Antonides, et al. 2015; Antonides, et al. 2015; Clouard, et al. 2016 ; Gieling, et al. 201 1 }, suggesting that differences in RM performance were not caused by a reduced performance of the piglets fed the lactose-based formula.
A factor that might have affected the performance of the piglets in the holeboard task could be differences in stress levels between the two experimental groups. Stress is known to have a significant impact on spatial learning and memory {Conrad, et al. 2010 }, and the quality of carbohydrates (as measured by the glycemic index) consumed have been found to influence anxiety and stress in humans {Haghighatdoost, et al. 2016 } and animals. In our study, however, piglets have been extensively habituated to the task, the experimenters, and the apparatus before the start of the acquisition phase. After this phase of habituation, piglets selected for testing did not show any extreme stress responses, such as escape attempts, suggesting that differences in stress levels between groups were very unlikely to explain the effect of the formula on RM performance.
No effects of the formula were found on IVI and trial duration, during either the acquisition or transition phase. These results indicate that animals were equally motivated and physically able to perform the task {Gieling, et al. 201 1 ; van der Staay, et al. 2012 }, and that differences of performance were not due to motivational factors or locomotor problems. The absence of motivational bias for the sweet food rewards in the holeboard seems to be supported by data from the single-solution consumption tests conducted after the end of the holeboard test, in which the formula had no effect on the intake of sweet caloric (sucrose) or non-caloric (sucralose) solutions. As early life carbohydrates play an important role in the development of food preferences and the consumption of sweet, high-energy food later in life {Stephen, et al. 2012 }, we expected that the intake of formulas containing different carbohydrates in early life would influence preference for sweet caloric or sweet non-caloric compounds later in life. Contrarily to our postulate, however, replacing lactose by maltodextrin in milk formulas did not alter long-term preferences (up to 8 wk after the end of the intervention) of piglets for sweet, caloric beverages; differences in motivation for the sweet, caloric food rewards used in the holeboard (chocolate raisins) were, therefore, very unlikely. As neither motivation, locomotion or stress seem to explain the differences of performance found in the holeboard task, it is safe to assume that the higher RM performance of the piglets fed the maltodextrin-based formula in the holeboard task reflects enhanced spatial long-term memory perse.
The effect of the formulas on long-term memory performance could be linked to differences in glucose availability in early life, as the brain appears to be sensitive to short-term variation in the availability of glucose (Grantham-McGregor 1987). Continuous glucose supply (to provide the brain with the required glucose for its high metabolism) is important for brain energy requirement but also its growth in animals, including pigs and humans {Vannucci, et al. 2000 }, and even more importantly in toddlers and young children than in adults (Bellisle, et al. 2004). It is well established that poor glucose supply or regulation is a risk factor for impaired cognitive development {Vannucci, et al. 2000 } and functioning (Philippou and Constantinou 2014). Lactose is a disaccharide of glucose and galactose compared to maltodextrin which comes from starch and made of only glucose units. Carbohydrate source in milk has been shown to modulate glucose regulation in humans (Innis and Novak 2014) which could suggest a difference in glucose availability for brain between piglets fed lactose or maltodextrin-based formulas. The type of carbohydrates (glucose-syrup DE 24, a starch derivative vs. lactose) in infant formula has been found to slightly modify metabolic post-prandial responses of formula-fed infants {Slupsky, 2017 }. Glycaemic load linked to food intake seems to influence cognitive functioning (Philippou and Constantinou 2014; Bellisle, et al. 2004; Ingwersen, et al. 2007; Micha, et al. 2011) but it remains to determine which variables of glucose metabolism are most strongly associated with cognition. It is thus possible that persistent changes in glucose metabolism in the early postnatal period shaped brain development and long term cognitive function of piglets in our study, possibly by impacting the supply of fuel needed for brain functioning. Although the mechanisms underlying these effects remain unclear, carbohydrate sources in early life impacted the RM performance during the acquisition and transition phases, whereas WM seemed to be unaffected. This finding is consistent with prior research showing differential effects of early life factors (e.g. dietary iron deficiency, low birth weight) on WM and RM performance {Antonides, et al. 2015;Gieling, et al. 2012;Prickaerts, et al. 1999 }, which are two independent components of spatial memory {Niewoehner, et al. 2007 }. Although the hippocampus is thought to be required for both reference and working memory when it comes to spatial cognition {Floresco, et al. 1997;Steele, et al. 1999 }, lesion studies indicate differential effects of hippocampal alterations on RM and WM. Inactivation of the medial prefrontal cortex have been found to impair spatial WM, but not RM, of rats in a delayed alternation task. On the contrary, inactivation of the dorsal hippocampus increased RM errors {Yoon, et al. 2008 }. Lesions of the hippocampus, but not of the prefrontal cortex, also impaired spatial RM performance of rats in a water maze {Pothuizen, et al. 2004 }{Sloan, et al. 2006 }. That RM, but not WM, was affected by the early carbohydrate source in our study may indicate that hippocampal development, in particular, has been affected by the nutritional intervention. The duration of hippocampal growth in pigs is significantly longer than that of the cortex, i.e. 9 vs. 6 weeks {Conrad, et al. 2012 }. The critical windows for early nutritional influences is, therefore, larger for the development of the hippocampus than that of cortical structures, such as the prefrontal cortex, which may render the hippocampus more sensitive to early nutritional interventions.
Piglets took more time to finish the trial and to find the first reward, made more visits and more RM errors, and had lower RM scores during the first reversal trials (i.e. after the switch of configuration) than during the last acquisition trials, whatever the milk formula. This drop in performance illustrates the difficulty for the piglets to adapt to an unexpected change in baits location, as reported previously {Gieling, et al. 2012 }. Interestingly, RM performance of piglets fed the maltodextrin-based formula was improved not only during acquisition, but also during the transition phase (i.e. around the switch of configuration), suggesting that piglets fed the maltodextin-based formulas had better cognitive flexibility, that is a higher ability to cope with an unexpected change in the task {Gieling, et al. 2012 }{van der Staay, et al. 2012 }. Although the effect was not statistically significant (data not shown), visual analyse of the data seems to support our postulate, with piglets fed the maltodextrin-based formula making (numerically) fewer visits and finding the first reward faster than the lactose group in the first block of reversal trials (Figure 2). Replicate studies on a larger set of animals are warranted to confirm or disprove this postulate.
In conclusion, piglets fed the maltodextrin-based formula showed improvement of spatial reference, /.e. long-term, memory in a holeboard task, even weeks after the end of the dietary intervention. Using maltodextrin in the infant formulas fed in early life did not affect growth or long-term preferences for sweet caloric or non-caloric beverages compared to a lactose-based formula. This is the first study showing, in the porcine model, that maltodextrin-based infant formulas are safe for growth and neurocognitive development.
Antonides, A., Schoonderwoerd, A. C., Nordquist, R. E., and van der Staay, F. J. (2015) Very low birth weight piglets show improved cognitive performance in the spatial cognitive holeboard task. Front Behav Neurosci 9, 43
Antonides, A., Schoonderwoerd, A. C., Scholz, G., Berg, B. M., Nordquist, R. E., and van der Staay, F. J. (2015) Pre-weaning dietary iron deficiency impairs spatial learning and memory in the cognitive holeboard task in piglets. Front Behav Neurosci 9, 291
Baldwin, B. A. (1976) Quantitative Studies on Taste Preference in Pigs. P Nutr Soc 35, 69-73
Benton, D., and a.i.s.b.l, I. E. (2008) The influence of children's diet on their cognition and behavior. Eur J Nutr 47 Suppl 3, 25-37
Bolton, J. L, and Bilbo, S. D. (2014) Developmental programming of brain and behavior by perinatal diet: focus on inflammatory mechanisms. Dialogues Clin Neurosci 16, 307-320
Caravas, J., and Wildman, D. E. (2014) A genetic perspective on glucose consumption in the cerebral cortex during human development. Diabetes Obes Metab 16 Suppl 1, 21-25
Clouard, C., Meunier-Salaun, M. C., and Val-Laillet, D. (2012) Food preferences and aversions in human health and nutrition: how can pigs help the biomedical research? Animal 6, 118-136 Clouard, C., Kemp, B., Val-Laillet, D., Gerrits, W. J., Bartels, A. C., and Bolhuis, J. E. (2016) Prenatal, but not early postnatal, exposure to a Western diet improves spatial memory of pigs later in life and is paired with changes in maternal prepartum blood lipid levels. FASEB J 30, 2466-2475
Cole, D. J. A., Duckwort.Je, and Holmes, W. (1967) Factors Affecting Voluntary Feed Intake in Pigs .1. Effect of Digestible Energy Content of Diet on Intake of Castrated Male Pigs Housed in Holding Pens and in Metabolism Crates. Anim Prod 9, 141-&
Conrad, C. D. (2010) A critical review of chronic stress effects on spatial learning and memory. Prog Neuropsychopharmacol Biol Psychiatry 34, 742-755
Conrad, M. S., Dilger, R. N., and Johnson, R. W. (2012) Brain growth of the domestic pig (Sus scrofa) from 2 to 24 weeks of age: a longitudinal MR! study. Developmental neuroscience 34, 291-298
Crisa, A. (2013) Milk carbohydrates and oligosaccharides. In Milk and dairy products in human nutrition: Production, composition and health (Park, Y. W., and Haenlein, G. F. W., eds) pp. 129-147, John Wiley & Sons, Ltd
CVB. (2008) CVB Table Booklet Feeding of Pigs: Feeding standards, feeding advices and nutritional values of feeding ingredients. CVB-series no 43, The Hague, The Netherlands
Dilger, R. N., and Johnson, R. W. (2010) Behavioral assessment of cognitive function using a translational neonatal piglet model. Brain Behav Immun 24, 11 Se ll 65
Dobbing, J., and Sands, J. (1979) Comparative aspects of the brain growth spurt. Early Hum Dev 3, 79-83
EFSA. (2014) Essential composition of infant and follow-on formulae. EFSA Journal 12
European Commission (2015) Commission Delegated Regulation (EU) 2016/127 of 25 September 2015 supplementing Regulation No 609/2013 of the European Parliament and the Council as regards the specific compositional and information requirements for infant formula and follow-on formula and as regards requirements on information relating to infant and young child feeding. In Official Journal of the European Union
Floresco, S. B., Seamans, J. K., and Phillips, A. G. (1997) Selective roles for hippocampal, prefrontal cortical, and ventral striatal circuits in radial-arm maze tasks with or without a delay. The Journal of neuroscience : the official journal of the Society for Neuroscience 17, 1880-1890
Gieling, E. T, Nordquist, R. E., and van der Staay, F. J. (2011) Assessing learning and memory in pigs. Anim Cogn 14, 151-173
Gieling, E. T., Park, S. Y., Nordquist, R. E., and van der Staay, F. J. (2012) Cognitive performance of low- and normal-birth-weight piglets in a spatial hole-board discrimination task. Pediatric research 71, 71-76
Glaser, D., Wanner, M., Tinti, J. M., and Nofre, C. (2000) Gustatory responses of pigs to various natural and artificial compounds known to be sweet in man. Food Chem 68, 375-385
Green Corkins, K., and Shurley, T. (2016) What's in the Bottle? A Review of Infant Formulas. Nutr Clin Pract
Haghighatdoost, F., Azadbakht, L, Keshteli, A. H., Feinle-Bisset, C., Daghaghzadeh, H., Afshar, H., Feizi, A., Esmaillzadeh, A., and Adibi, P. (2016) Glycemic index, glycemic load, and common psychological disorders. Am J Clin Nutr 103, 201-209
Heubi, J., Karasov, R., Reisinger, K., Blatter, M., Rosenberg, L, Vanderhoof, J., Darden, P. M., Safier, J., Martin, T., and Euler, A. R. (2000) Randomized multicenter trial documenting the efficacy and safety of a lactose-free and a lactose-containing formula for term infants. J Am Diet Assoc 100, 212-217
Hofman, D. L, van Buul, V. J., and Brouns, F. J. (2016) Nutrition, Health, and Regulatory Aspects of Digestible Maltodextrins. Critical reviews in food science and nutrition 56, 2091-2100
Kornum, B. R., and Knudsen, G. M. (2011) Cognitive testing of pigs (Sus scrofa) in translational biobehavioral research. Neurosci Biobehav Rev 35, 437-451
Krogh, U., Oksbjerg, N., Purup, S., Ramaekers, P., and Theil, P. K. (2016) Colostrum and milk production in multiparous sows fed supplementary arginine during gestation and lactation. J Anim Sci 94, 22-25
Lamport, D. J., Lawton, C. L, Mansfield, M. W., and Dye, L. (2009) Impairments in glucose tolerance can have a negative impact on cognitive function: a systematic research review. Neurosci Biobehav Rev 33, 394-413
Langley-Evans, S. C. (2009) Nutritional programming of disease: unravelling the mechanism. J Anat 215, 36-51 Lind, N. M., Moustgaard, A., Jelsing, J., Vajta, G., Cumming, P., and Hansen, A. K. (2007) The use of pigs in neuroscience: modeling brain disorders. Neurosci Biobehav Rev 31, 728-751
Maldonado, J., Gil, A., Narbona, E., and Molina, J. A. (1998) Special formulas in infant nutrition: a review. Early Hum Dev 53 Suppl, S23-32
Moody, L., Chen, H., and Pan, Y. X. (2017) Early-Life Nutritional Programming of Cognition-The Fundamental Role of Epigenetic Mechanisms in Mediating the Relation between Early-Life Environment and Learning and Memory Process. Adv Nutr 8, 337-350
Murphy, M., and Mercer, J. G. (2013) Diet-regulated anxiety. International journal of endocrinology 2013, 701967
Niewoehner, B., Single, F. N., Hvalby, O., Jensen, \/., Meyer zum Alien Borgloh, S., Seeburg, P. H., Rawlins, J. N., Sprengel, R., and Bannerman, D. M. (2007) Impaired spatial working memory but spared spatial reference memory following functional loss of NMD A receptors in the dentate gyrus. Eur J Neurosci 25, 837-846 Patel, M. S., Srinivasan, M., and Laychock, S. G. (2009) Metabolic programming: Role of nutrition in the immediate postnatal life. J Inherit Metab Dis 32, 218-228
Pothuizen, H. H., Zhang, W. N., Jongen-Relo, A. L., Feldon, J., and Yee, B. K. (2004) Dissociation of function between the dorsal and the ventral hippocampus in spatial learning abilities of the rat: a within-subject, within-task comparison of reference and working spatial memory. Eur J Neurosci 19, 705-712
Prickaerts, J., Honig, W., Schmidt, B. H., and Blokland, A. (1999) Metrifonate improves working but not reference memory performance in a spatial cone field task. European journal of pharmacology 380, 61-65
Roura, E., Koopmans, S. J., Lalles, J. P., Le Huerou-Luron, I., de Jager, N., Schuurman, T, and Val-Laillet, D. (2016) Critical review evaluating the pig as a model for human nutritional physiology. Nutr Res Rev 29, 60-90
Sloan, H. L, Good, M., and Dunnett, S. B. (2006) Double dissociation between hippocampal and prefrontal lesions on an operant delayed matching task and a water maze reference memory task. Behav Brain Res 171, 116-126
Slupsky, C. M., He, X., Hernell, O., Andersson, Y., Rudolph, C., Lonnerdal, B., and West, C. E. (2017) Postprandial metabolic response of breast-fed infants and infants fed lactose-free vs regular infant formula: A randomized controlled trial. Sci Rep 7, 3640
Souza, C. G., Moreira, J. D., Siqueira, I. R., Pereira, A. G., Rieger, D. K., Souza, D. O., Souza, T. M., Portela, L. V., and Perry, M. L. (2007) Highly palatable diet consumption increases protein oxidation in rat frontal cortex and anxiety-like beha vior. Life sciences 81, 198-203
Steele, R. J., and Morris, R. G. (1999) Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA- antagonist D-AP5. Hippocampus 9, 118-136
Stephen, A., Alles, M., de Graaf, C., Fleith, M., Hadjilucas, E., Isaacs, E.,
Maffeis, C., Zeinstra, G., Matthys, C., and Gil, A. (2012) The role and requirements of digestible dietary carbohydrates in infants and toddlers. Eur J Clin Nutr 66, 765-779 Tzanetakou, I. P., Mikhailidis, D. P., and Perrea, D. N. (2011) Nutrition During Pregnancy and the Effect of Carbohydrates on the Offspring's Metabolic Profile: In Search of the "Perfect Maternal Diet". Open Cardiovasc Med J 5, 103-109
van der Staay, F. J., Gieling, E. , Pinzon, N. E., Nordquist, R. E., and Ohl, F. (2012) The appetitively motivated "cognitive" holeboard: a family of complex spatial discrimination tasks for assessing learning and memory. Neurosci Biobehav Rev 36, 379-403
Vannucci, R. C., and Vannucci, S. J. (2000) Glucose metabolism in the developing brain. Semin Perinatol 24, 107-115
Yoon, T, Okada, J., Jung, M. W., and Kim, J. J. (2008) Prefrontal cortex and hippocampus subserve different components of working memory in rats. Learn Mem 15, 97-105

Claims

C L A I M S
1. Use of a digestible maltodextrin having a dextrose equivalent (DE) of between 15 to 19 or a composition comprising thereof in the early childhood of a mammal for enhancing or improving cognition and/or stimulating brain development at adult age of said mammal.
2. The use according to claim 1 , wherein the cognitive performance is the cognitive flexibility of said mammal.
3. The use according to claim 1 , wherein the cognitive performance is the memory of said mammal.
4. The use according to claim 3, wherein the cognitive performance is the long term memory of said mammal.
5. The use according to claim 1 , wherein the maltodextrins stimulate the development of the area of the brain which responsible of spatial cognition.
6. The use according to claim 5, wherein the area responsible of spatial cognition is the hippocampus.
7. The use according to one of the claims 1 to 6, wherein the composition comprises 20 to 30 % of proteins, preferably vegetable proteins and/or animal proteins; 20 to 40% of maltodextrin and 20 to 40% of fat.
8. The use according to claims 1 to 7, wherein the composition is a formula-fed infant or a growing up milk.
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2327733A1 (en) * 1975-10-16 1977-05-13 Lyall Neil Powdered whole milk substitute - contg. whey or malto-dextrin as filler, hardened plant oil, sweetener and emulsifier
FR2884422A1 (en) 2005-04-18 2006-10-20 Roquette Freres ANTI-INFLAMMATORY COMPOSITION OF INTESTINES COMPRISING BRANCHED MALTODEXTRINS
EP2422629A1 (en) 2010-08-23 2012-02-29 Abbott Laboratories Methods for enhancing cognition and/or memory using maltodextrins
US20140187514A1 (en) * 2005-02-09 2014-07-03 Vifor (International) Ag Use Of Iron(III) Complex Compounds
CN106615178A (en) * 2017-01-13 2017-05-10 汉臣氏（沈阳）儿童制品有限公司 Solid DHA (docosahexaenoic acid) algae oil beverage

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2327733A1 (en) * 1975-10-16 1977-05-13 Lyall Neil Powdered whole milk substitute - contg. whey or malto-dextrin as filler, hardened plant oil, sweetener and emulsifier
US20140187514A1 (en) * 2005-02-09 2014-07-03 Vifor (International) Ag Use Of Iron(III) Complex Compounds
FR2884422A1 (en) 2005-04-18 2006-10-20 Roquette Freres ANTI-INFLAMMATORY COMPOSITION OF INTESTINES COMPRISING BRANCHED MALTODEXTRINS
US20080182821A1 (en) * 2005-04-18 2008-07-31 Roquette Freres Anti-Inflammatory and/or Analgesic Composition For the Intestine Comprising Branched Maltodextrins
EP2422629A1 (en) 2010-08-23 2012-02-29 Abbott Laboratories Methods for enhancing cognition and/or memory using maltodextrins
CN106615178A (en) * 2017-01-13 2017-05-10 汉臣氏（沈阳）儿童制品有限公司 Solid DHA (docosahexaenoic acid) algae oil beverage

Non-Patent Citations (46)

* Cited by examiner, † Cited by third party
Title
ANTONIDES, A.; SCHOONDERWOERD, A. C.; NORDQUIST, R. E.; VAN DER STAAY, F. J.: "Very low birth weight piglets show improved cognitive performance in the spatial cognitive holeboard task", FRONT BEHAV NEUROSCI, vol. 9, 2015, pages 43
ANTONIDES, A.; SCHOONDERWOERD, A. C.; SCHOLZ, G.; BERG, B. M.; NORDQUIST, R. E.; VAN DER STAAY, F. J.: "Pre-weaning dietary iron deficiency impairs spatial learning and memory in the cognitive holeboard task in piglets", RONT BEHAV NEUROSCI, vol. 9, 2015, pages 291
BALDWIN, B. A.: "Quantitative Studies on Taste Preference in Pigs", P NUTR SOC, vol. 35, 1976, pages 69 - 73
BENTON, D.; A.I.S.B.L, I. E.: "The influence of children's diet on their cognition and behavior", EUR J NUTR, vol. 47, 2008, pages 25 - 37, XP019628485
BOLTON, J. L.; BILBO, S. D.: "Dialogues Clin Neurosci", DEVELOPMENTAL PROGRAMMING OF BRAIN AND BEHAVIOR BY PERINATAL DIET: FOCUS ON INFLAMMATORY MECHANISMS, vol. 16, 2014, pages 307 - 320
CARAVAS, J.; WILDMAN, D. E.: "A genetic perspective on glucose consumption in the cerebral cortex during human development", DIABETES OBES METAB, vol. 1, 2014, pages 21 - 25
CLOUARD, C.; KEMP, B.; VAL-LAILLET, D.; GERRITS, W J.; BARTELS, A. C.; BOLHUIS, J. E.: "Prenatal, but not early postnatal, exposure to a Western diet improves spatial memory of pigs later in life and is paired with changes in maternal prepartum blood lipid levels", FASEB J, vol. 30, 2016, pages 2466 - 2475
CLOUARD, C.; MEUNIER-SALAUN, M. C.; VAL-LAILLET, D.: "Food preferences and aversions in human health and nutrition: how can pigs help the biomedical research", ANIMAL, vol. 6, 2012, pages 118 - 136
COLE, D. J. A.; DUCKWORT.JE; HOLMES, W: "Factors Affecting Voluntary Feed Intake in Pigs .1. Effect of Digestible Energy Content of Diet on Intake of Castrated Male Pigs Housed in Holding Pens and in Metabolism Crates", ANIM PROD, vol. 9, 1967, pages 141
CONRAD, C. D.: "Prog Neuropsychopharmacol Biol Psychiatry", A CRITICAL REVIEW OF CHRONIC STRESS EFFECTS ON SPATIAL LEARNING AND MEMORY, vol. 34, 2010, pages 742 - 755
CONRAD, M. S.; DILGER, R. N.; JOHNSON, R. W.: "Brain growth of the domestic pig (Sus scrofa) from 2 to 24 weeks of age: a longitudinal MRI study", DEVELOPMENTAL NEUROSCIENCE, vol. 34, 2012, pages 291 - 298
CRISA, A.: "In Milk and dairy products in human nutrition: Production, composition and health", 2013, JOHN WILEY & SONS, LTD, article "Milk carbohydrates and oligosaccharides", pages: 129 - 147
CVB: "CVB Table Booklet Feeding of Pigs: Feeding standards, feeding advices and nutritional values of feeding ingredients", CVB-SERIES NO 43, THE HAGUE, 2008
DILGER, R. N.; JOHNSON, R. W.: "Behavioral assessment of cognitive function using a translational neonatal piglet model", BRAIN BEHAV IMMUN, vol. 24, 2010, pages 1156 - 1165, XP027278948
DOBBING, J.; SANDS, J.: "Comparative aspects of the brain growth spurt", EARLY HUM DEV, vol. 3, 1979, pages 79 - 83, XP026198841, DOI: doi:10.1016/0378-3782(79)90022-7
EFSA: "Essential composition of infant and follow-on formulae", EFSA JOURNAL 12, 2014
FLORESCO, S. B.; SEAMANS, J. K.,; PHILLIPS, A. G.: "Selective roles for hippocampal, prefrontal cortical, and ventral striatal circuits in radial-arm maze tasks with or without a delay", THE JOURNAL OF NEUROSCIENCE : THE OFFICIAL JOURNAL OF THE SOCIETY FOR NEUROSCIENCE, vol. 17, 1997, pages 1880 - 1890
GIELING, E. T.; NORDQUIST, R. E.; VAN DER STAAY, F. J.: "Assessing learning and memory in pigs", ANIM COGN, vol. 14, 2011, pages 151 - 173, XP019882498, DOI: doi:10.1007/s10071-010-0364-3
GIELING, E. T.; PARK, S. Y.; NORDQUIST, R. E.; VAN DER STAAY, F. J.: "Cognitive performance of low- and normal-birth-weight piglets in a spatial hole-board discrimination task", PEDIATRIC RESEARCH, vol. 71, 2012, pages 71 - 76
GLASER, D.; WANNER, M.; TINTI, J. M.; NOFRE, C.: "Gustatory responses of pigs to various natural and artificial compounds known to be sweet in man", FOOD CHEM, vol. 68, 2000, pages 375 - 385, XP000884165, DOI: doi:10.1016/S0308-8146(99)00212-5
GREEN CORKINS, K.; SHURLEY, T.: "What's in the Bottle? A Review of Infant Formulas", NUTR CLIN PRACT, 2016
HAGHIGHATDOOST, F.; AZADBAKHT, L.; KESHTELI, A. H.; FEINLE-BISSET, C.; DAGHAGHZADEH, H.; AFSHAR, H.; FEIZI, A.; ESMAILLZADEH, A.;: "Glycemic index, glycemic load, and common psychological disorders", AM J CLIN NUTR, vol. 103, 2016, pages 201 - 209
HEUBI, J.; KARASOV, R.; REISINGER, K.; BLATTER, M.; ROSENBERG, L.; VANDERHOOF, J.; DARDEN, P. M.; SAFIER, J.; MARTIN, T.; EULER, A: "Randomized multicenter trial documenting the efficacy and safety of a lactose-free and a lactose-containing formula for term infants", J AM DIET ASSOC, vol. 100, 2000, pages 212 - 217
HOFMAN, D. L.; VAN BUUL, V. J.; BROUNS, F. J.: "Nutrition, Health, and Regulatory Aspects of Digestible Maltodextrins", CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION, vol. 56, 2016, pages 2091 - 2100
KORNUM, B. R.; KNUDSEN, G. M.: "Cognitive testing of pigs (Sus scrofa) in translational biobehavioral research", NEUROSCI BIOBEHAV REV, vol. 35, 2011, pages 437 - 451, XP027552994
KROGH, U.; OKSBJERG, N.; PURUP, S.; RAMAEKERS, P.; THEIL, P. K.: "Colostrum and milk production in multiparous sows fed supplementary arginine during gestation and lactation", J ANIM SCI, vol. 94, 2016, pages 22 - 25
LAMPORT, D. J.; LAWTON, C. L.; MANSFIELD, M. W,; DYE, L.: "Impairments in glucose tolerance can have a negative impact on cognitive function: a systematic research review", NEUROSCI BIOBEHAV REV, vol. 33, 2009, pages 394 - 413, XP025913467, DOI: doi:10.1016/j.neubiorev.2008.10.008
LANGLEY-EVANS, S. C.: "Nutritional programming of disease: unravelling the mechanism", J ANAT, vol. 215, 2009, pages 36 - 51
LIND, N. M.; MOUSTGAARD, A.,; JELSING, J.; VAJTA, G.; CUMMING, P.; HANSEN, A. K.: "The use of pigs in neuroscience: modeling brain disorders", NEUROSCI BIOBEHAV REV, vol. 31, 2007, pages 728 - 751, XP022060939, DOI: doi:10.1016/j.neubiorev.2007.02.003
MALDONADO, J.; GIL, A.; NARBONA, E.; MOLINA, J. A.: "Special formulas in infant nutrition: a review", EARLY HUM DEV 53 SUPPL, 1998, pages S23 - 32
MOODY, L.; CHEN, H.; PAN, Y. X.: "Early-Life Nutritional Programming of Cognition-The Fundamental Role of Epigenetic Mechanisms in Mediating the Relation between Early-Life Environment and Learning and Memory Process", ADV NUTR, vol. 8, 2017, pages 337 - 350
MURPHY, M.; MERCER, J. G.: "Diet-regulated anxiety", INTERNATIONAL JOURNAL OF ENDOCRINOLOGY, 2013, pages 701967
NIEWOEHNER, B.; SINGLE, F. N.; HVALBY, O.; JENSEN, V.; MEYER ZUM ALTEN BORGLOH, S.; SEEBURG, P. H.; RAWLINS, J. N.; SPRENGEL, R.;: "Impaired spatial working memory but spared spatial reference memory following functional loss of NMDA receptors in the dentate gyrus", EUR J NEUROSCI, vol. 25, 2007, pages 837 - 846
PATEL, M. S.; SRINIVASAN, M.; LAYCHOCK, S. G.: "Metabolic programming: Role of nutrition in the immediate postnatal life", J INHERIT METAB DIS, vol. 32, 2009, pages 218 - 228, XP019671019
POTHUIZEN, H. H.; ZHANG, W N.; JONGEN-RELO, A. L.; FELDON, J.; YEE, B. K.: "Dissociation of function between the dorsal and the ventral hippocampus in spatial learning abilities of the rat: a within-subject, within-task comparison of reference and working spatial memory", EUR J NEUROSCI, vol. 19, 2004, pages 705 - 712
PRICKAERTS, J.; HONIG, W, SCHMIDT, B. H.; BLOKLAND, A.: "Metrifonate improves working but not reference memory performance in a spatial cone field task", EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 380, 1999, pages 61 - 65
ROURA, E.; KOOPMANS, S. J.; LALLES, J. P.; LE HUEROU-LURON, I.; DE JAGER, N.; SCHUURMAN, T.; VAL-LAILLET, D.: "Critical review evaluating the pig as a model for human nutritional physiology", NUTR RES REV, vol. 29, 2016, pages 60 - 90
SLOAN, H. L.; GOOD, M.; DUNNETT, S. B.: "Double dissociation between hippocampal and prefrontal lesions on an operant delayed matching task and a water maze reference memory task", BEHAV BRAIN RES, vol. 171, 2006, pages 116 - 126, XP025031748, DOI: doi:10.1016/j.bbr.2006.03.030
SLUPSKY, C. M.; HE, X.; HERNELL, O.; ANDERSSON, Y.; RUDOLPH, C.; LONNERDAL, B.; WEST, C. E.: "Postprandial metabolic response of breast-fed infants and infants fed lactose-free vs regular infant formula: A randomized controlled trial", SCI REP, vol. 7, 2017, pages 3640
SOUZA, C. G.; MOREIRA, J. D.; SIQUEIRA, I. R.; PEREIRA, A. G.; RIEGER, D. K.; SOUZA, D. O.; SOUZA, T. M.; PORTELA, L. V.; PERRY, M: "Highly palatable diet consumption increases protein oxidation in rat frontal cortex and anxiety-like behavior", LIFE SCIENCES, vol. 81, 2007, pages 198 - 203, XP022133087, DOI: doi:10.1016/j.lfs.2007.05.001
STEELE, R. J.; MORRIS, R. G.: "Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-antagonist D-AP5", HIPPOCAMPUS, vol. 9, 1999, pages 118 - 136
STEPHEN, A.; ALLES, M.; DE GRAAF, C.; FLEITH, M.; HADJILUCAS, E.; ISAACS, E.; MAFFEIS, C.; ZEINSTRA, G.; MATTHYS, C.; GIL, A.: "The role and requirements of digestible dietary carbohydrates in infants and toddlers", EUR J CLIN NUTR, vol. 66, 2012, pages 765 - 779
TZANETAKOU, I. P.; MIKHAILIDIS, D. P.; PERREA, D. N.: "Nutrition During Pregnancy and the Effect of Carbohydrates on the Offspring's Metabolic Profile: In Search of the ''Perfect Maternal Diet''", OPEN CARDIOVASC MED J, vol. 5, 2011, pages 103 - 109
VAN DER STAAY, F. J.; GIELING, E. T.; PINZON, N. E.; NORDQUIST, R. E.; OHL, F.: "The appetitively motivated ''cognitive'' holeboard: a family of complex spatial discrimination tasks for assessing learning and memory", NEUROSCI BIOBEHAV REV, vol. 36, 2012, pages 379 - 403, XP028119116, DOI: doi:10.1016/j.neubiorev.2011.07.008
VANNUCCI, R. C.; VANNUCCI, S. J.: "Glucose metabolism in the developing brain", SEMIN PERINATOL, vol. 24, 2000, pages 107 - 115, XP009026677, DOI: doi:10.1053/sp.2000.6361
YOON, T.; OKADA, J.; JUNG, M. W.; KIM, J. J.: "Prefrontal cortex and hippocampus subserve different components of working memory in rats", LEARN MEM, vol. 15, 2008, pages 97 - 105

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