CN101384184A - 用于预防肥胖症的婴儿营养组合物 - Google Patents

用于预防肥胖症的婴儿营养组合物 Download PDF

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CN101384184A
CN101384184A CNA2006800533029A CN200680053302A CN101384184A CN 101384184 A CN101384184 A CN 101384184A CN A2006800533029 A CNA2006800533029 A CN A2006800533029A CN 200680053302 A CN200680053302 A CN 200680053302A CN 101384184 A CN101384184 A CN 101384184A
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CN101384184B (zh
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R·M·L·兹威杰森
G·斯佩尔曼斯
E·M·范德贝克
G·贝姆
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Nutricia NV
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Nutricia NV
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Priority claimed from PCT/NL2006/050274 external-priority patent/WO2008054192A1/en
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Abstract

本发明涉及通过向0－36月龄的婴儿给药某营养组合物来预防其在以后的生命中罹患肥胖症的方法。

Description

用于预防肥胖症的婴儿营养组合物
技术领域
本发明涉及通过向年龄低于3岁的非肥胖婴儿给药特别的营养组合物来预防其在以后的生命中罹患肥胖症的方法。
背景技术
母乳喂养是喂养婴儿的优选方法。但是有些情况下不可能或不那么期望进行母乳喂养。在这些情况下，婴儿配方是很好的替代选择。现代婴儿配方的组成适合于快速生长和发育中的婴儿的多种特殊营养需求。
但是婴儿奶乳配方的组成似乎可以进一步改进。例如，对于婴儿配方中的成分对在其以后的生命中罹患肥胖症的影响就知之甚少。本发明涉及这种未来健康考虑。
WO 2005063050描述了通过向足月儿或早产儿给药含有DHA和ARA源的营养配方来增加婴儿瘦体重并降低其脂肪量的方法。WO 2006057551涉及含有至少一种蛋白酶抑制剂的婴儿营养剂、制备这种婴儿营养剂的方法和该婴儿营养剂用于治疗和/或预防儿童肥胖症及其继发性病症的用途。WO 03005836描述了婴儿、儿童和成人营养饮食产品，其具有足够水平和比例的中链脂肪酸和ω多不饱和脂肪酸。消费这些饮食产品可有助于预防发育中的个体罹患肥胖症并可有助于在试图减轻体重或降低体脂量的人(例如，肥胖的个体)中降低体脂量。WO 2006069918描述了在婴儿出生后的前几个月内持续降低循环中胰岛素样生长因子1(IGF-1)的水平的方法，该方法是向所述婴儿给药含有蛋白质的营养组合物，所述蛋白质的量为使得所述组合物每100kcal含有不到2.25g的蛋白质。因为IGF-1已知是生长营养调控的关键控制点，因此这可能提供降低以后生命中罹患肥胖症的风险的方法。Aillaud等，2006，Progress in Lipid research 45:203-206，讨论了n-6多不饱和脂肪酸在过度的脂肪组织形成中的作用以及其与肥胖症的关系。
发明内容
婴儿期内，体脂特别是皮下脂肪对于维持充分的体温和储存能量具有重要功能。因此，一般不期望在婴儿中降低体脂量，因为这会干扰健康生长和发育。因此本发明的主要目的是设计向婴儿给药的营养剂，其在婴儿期内保证维持正常的身体组成、生长和发育，但在以后的生命中(即婴儿期后)，优选在青春期和/或成年期，降低过多的体脂量的堆积。
本发明的发明人通过实验证明在生命早期给药其中脂质组分中亚油酸(LA)相对较低并且亚油酸/α-亚麻酸比例(LA/ALA)低的营养剂，在以后的生命中导致降低的脂肪量堆积，特别是降低的内脏脂肪堆积。在这些实验中，小鼠在生命早期接受特定的营养剂(LA含量低且LA/ALA比例低)，而对照组未接受该特定的营养剂。在后来的生命阶段，各组动物接受同样的饱和脂肪含量较高的饮食。令人惊讶的是，在婴儿期未观察到对生长和体脂总量的影响，但与对照组相比，在生命早期用该实验营养剂饲喂的小鼠在生命的青春期和成年期阶段，观察到降低的体脂总量，特别是降低的内脏脂肪量。实验结果表明本发明的婴儿营养组合物对在以后的生命中罹患肥胖症的影响，特别是对年龄高于36个月，即儿童期(3-12岁)、青春期(13-18岁)和成年期(18岁以上)的影响。
因此，本发明涉及用于预防年龄高于36个月的人类婴儿罹患肥胖症的方法，换言之，涉及用于预防在以后生命中罹患肥胖症的方法，所述方法包括向年龄低于36个月的婴儿给药包含脂质、蛋白质和可消化碳水化合物组分的营养组合物，，其中所述脂质组分包含亚油酸(LA)和α-亚麻酸(ALA)，其重量比例LA/ALA为2-7；低于总脂肪酸的15重量％的LA；和至少为总脂肪酸的1重量％的ALA。
对于某些法律管辖区域，本发明也被描述为包含脂质、蛋白质和可消化碳水化合物组分的组合物用于制备给药于年龄低于36个月的(非肥胖)婴儿以预防肥胖症的营养组合物的用途，其中所述脂质组分包含(i)亚油酸(LA)和α-亚麻酸(ALA)，其重量比例LA/ALA为2-7；(ii)低于总脂肪酸的15重量％的LA，(iii)至少为总脂肪酸的1重量％的ALA。本发明优选被描述为给药于年龄低于36个月的非肥胖人类的组合物，所述组合物包含脂质、蛋白质和可消化碳水化合物组分，其中所述脂质组分包含亚油酸(LA)和α-亚麻酸(ALA)，其重量比例LA/ALA为2-7；低于总脂肪酸的15重量％的LA；和超过总脂肪酸的1重量％的ALA，所述组合物用于预防所述人类年龄高于36个月时罹患病症具体而言为肥胖症。
此外，发明人意识到为预防以后的生命中罹患肥胖症而设计LA含量较低且LA/ALA比例较低的婴儿营养剂可能会不利于LA和n-6长链多不饱和脂肪酸(LC-PUFA)的生物利用度和其进入神经组织例如脑和视网膜的膜内的情况，其中所述n-6 LC-PUFA经生物合成由LA得到，例如花生四烯酸(AA)。LA与特别是AA是脑磷脂的重要前体，因此对婴儿极为重要，特别是对于视觉系统、脑、智力和认知能力(以后的生命中)的发展极为重要。为防止低LA水平产生的副作用，刺激膜形成和包含在脑和其它神经组织中支持膜形成的组分非常重要。因此，本发明提供降低以后的生命中(即婴儿期以后)过多体脂量的堆积的低LA营养剂，其包含至少一种选自于(i)磷脂；(ii)鞘脂；(iii)胆固醇，和/或(iv)尿苷和胆碱的组分。在本发明的低LA配方中包含该组分增加PUFA、特别是n-6PUFA的生物利用度以进入细胞膜，和/或降低n-6(LC-)PUFA的氧化。尿苷和胆碱的混合物增加磷脂的形成。因此，在本发明的低LA组合物中包含一种或多种这些组分有利地刺激最佳的脑发育，因为它增加每个细胞的膜磷脂的量。本发明的另一目的是提供胰岛素反应较弱的低LA配方。
发明详述
本发明提供含有脂质、蛋白质和可消化碳水化合物组分的组合物用于制备给药于年龄低于36个月的(非肥胖)婴儿以预防肥胖症的营养组合物的用途，其中所述脂质组分包含：
(i)亚油酸(LA)和α-亚麻酸(ALA)，其重量比例LA/ALA为2-7；
(ii)低于总脂肪酸的15重量％的LA，和
(iii)至少为总脂肪酸的1重量％的ALA；
且其中所述组合物进一步包含至少一种选自于下组的组分：
(a)占总脂肪0.5-20重量％的磷脂；
(b)占总脂肪0.5-20重量％的鞘脂；
(c)占总脂肪0.005-10重量％的胆固醇；和
(d)占所述组合物干重0.035-1重量％的胆碱和占所述组合物干
重0.001-0.1重量％的尿苷。
本发明的另一方面提供含有脂质、蛋白质、可消化碳水化合物(例如本发明的低LA组合物)和胆固醇的组合物用于制备给药于年龄低于36个月的婴儿以预防其以后生命中罹患心血管疾病、动脉粥样硬化和/或血中胆固醇水平过高的营养组合物的用途
肥胖症
本发明的组合物给药于年龄低于36个月、优选低于18个月、更优选低于12个月、更优选低于6个月的非肥胖人类婴儿。优选本发明的组合物给药于年龄低于36个月、优选低于18个月、更优选低于12个月、更优选低于6个月的非超重的人类。婴儿是否患有肥胖症和/或是否超重可由医师适当地确定。通常年龄低于36个的非肥胖婴儿的性别特异性体重身高比低于95个百分点、更优选低于85个百分点。疾病控制和预防中心(CDC)于2000年发布了性别特异性体重身高比百分点表。
同样年龄高于36个月的人类个体是否患有肥胖症和/或是否体重超重也可以由医师容易地确定，和/或根据CDC发布的性别特异性体重身高比百分点表来确定。
健康相关的问题特别的与特殊形式的肥胖症即向心性肥胖相关。优选地，所述组合物用于预防以后的生命中的向心性肥胖。术语“向心性肥胖”是指内脏脂肪量增加的病症。成年男性腰围高于102厘米或成年女性腰围高于88厘米则表明具有向心性肥胖。对于3-19岁的儿童而言，在Taylor等，2000Am J Clin Nutr 72:490-495中可以找到适当的随年龄和性别而定的腰围截至值。
低LA组合物
这里LA是指亚油酸(18:2 n6)；ALA是指α-亚麻酸(18:3 n3)；LC-PUFA是指脂肪酰基链中包含至少20个碳原子且具有2个或多个不饱和键的长链多不饱和脂肪酸和/或酰基链；DHA是指二十二碳六烯酸(22:6，n3)；EPA是指二十碳五烯酸(20:5 n3)；ARA是指二十碳四烯酸(20:4 n6)；DPA是指二十二碳五烯酸(22:5 n3)，DHGLA是指双高亚麻酸(20:3 n6)。中链脂肪酸(MCFA)是指链长为6、8或10个碳原子的脂肪酸和/或酰基链。MCFA也可以被称为中链甘油三酯(MCT)。
本发明的发明人发现LA/ALA比例较低且LA含量较低的特定组合物预防肥胖症、特别是向心性肥胖的发生。特别是给药包含(i)LA/ALA重量比例为2-7且(ii)低含量LA(<总脂肪酸的15重量％)的营养组合物使以后的生命中罹患肥胖症的情况减少。
本发明的组合物包含脂质。LA应以足够量存在以促进健康生长和发育，但其量应尽量低以预防在以后的生命中发生肥胖症。因此所述组合物包含低于总脂肪酸的15重量％、优选5-14.5重量％、更优选6-12重量％的LA。基于组合物的总干重，本发明的组合物优选含有1.5-5重量％的LA。当为液体形式时，例如为即开即饮的配方时，LA含量优选为每100ml液体组合物0.2-0.55gLA。LA优选提供本发明的组合物总热量的4-8％。
ALA应以足够量存在以促进婴儿健康生长和发育。因此本发明的组合物包含至少占总脂肪酸1.0重量％的ALA。优选所述组合物包含至少占总脂肪酸1.6重量％、更优选至少2.0重量％的ALA。优选所述组合物包含低于总脂肪酸10重量％、更优选低于5.0重量％的ALA。基于组合物的总干重，本发明的组合物优选包含至少0.10重量％的ALA、优选0.10-0.8重量％的ALA。当为液体形式时，例如为即开即饮的配方时，ALA含量优选为每100ml液体组合物至少30mg ALA，优选每100ml50-150mg ALA。LA/ALA的重量比例应保持良好平衡以预防肥胖症特别是向心性肥胖，同时保证正常的生长和发育。本发明的发明人发现了适当的比例。本发明的组合物包含的LA/ALA的重量比为2-7、更优选3-6、更优选4-5.5，更优选4-5。脂质组分包含低于总脂肪酸的15重量％的LA且LA/ALA比例为2-7。
MCFA和LC-PUFA
还发现n-3 LC PUFA减少以后生命中肥胖症和向心性肥胖的发病，而MCFA只减少以后生命中一般肥胖症的发病。这一发现进一步使得能够开发最佳的组合物，其优选含有MCFA，但不过量，即占总脂肪酸的3-50重量％，和/或含有LC-PUFA(包括n-6 LC PUFA)，但n-6 LC-PUFA/n-3LC-PUFA比例较低。
中链脂肪酸(MCFA)是链长为6、8或10个碳原子的脂肪酸和/或酰基链。本发明的发明人还发现MCFA有助于在以后的生命中降低脂肪量。LA是必需脂肪酸，意味着身体无法合成LA。由于本发明的组合物的LA含量相对较低，因此重要的是本发明组合物中所含的LA不(通过脂肪氧化)被转化为能量，因此也不可被合成代谢过程利用。为减少本发明的低LA组合物中LA的氧化，可适当加入MCFA。MCFA在血流中容易地被动员以提供能量，而不作为脂肪储存起来，从而减少LA的氧化。因此本发明的组合物优选包含至少总脂肪酸3重量％的MCFA、更优选至少10重量％、更优选15重量％。
本发明的发明人发现MCFA降低体脂堆积但对于向心性脂肪量没有选择性。因此，本发明的低LA和低LA/ALA组合物的总脂肪酸中有利地含有低于50重量％、更优选低于40重量％、更优选低于25重量％的MCFA。
优选本发明的组合物包含LC-PUFA。本发明的发明人发现LC-PUFA减少以后生命中肥胖症、更优选向心性肥胖的发病。更优选本发明的组合物包含n-3LC-PUFA、更优选EPA、DPA和/或DHA、更优选DHA。已发现这些n-3LC-PUFA减少肥胖症的发病。
由于低浓度的DHA、DPA和/或EPA已经是有效的，且正常的生长和发育至关重要，因此本发明组合物中的n-3LC-PUFA含量优选不超过总脂肪酸含量的15重量％、优选不超过10重量％、更优选不超过5重量％。优选本发明的组合物含有占脂肪酸总含量的至少0.2重量％、优选至少0.5重量％、更优选至少0.75重量％的n-3LC-PUFA。由于同样的原因，EPA含量优选不超过总脂肪酸的5重量％、更优选不超过1重量％，但优选至少为总脂肪酸的0.025重量％、更优选至少0.05重量％。DHA含量优选不超过总脂肪酸的5重量％、更优选不超过1重量％，但优选至少为总脂肪酸的0.1重量％。DPA的含量优选不超过总脂肪酸含量的1重量％、更优选不超过0.5重量％，但优选至少为总脂肪酸的0.01重量％。优选地作为n-3 LC-PUFA源，使用单细胞油，优选使用海藻油、真菌油和/或微生物油，因为这些油源的EPA/DHA比例低，这导致增强的抗肥胖效果。更优选本发明的组合物含有鱼油(更优选金枪鱼油)。鱼油有更高的EPA浓度，由于EPA是具有额外抗肥胖效果的类花生酸的前体，因此格外有利。
由于n-6脂肪酸组特别是花生四烯酸(AA)和作为其前体的LA与n-3脂肪酸组特别是DHA、EPA和作为它们的前体的ALA互相抵消，因此本发明的组合物含有相对少量的AA。n-6 LC-PUFA的含量优选不超过总脂肪酸的5重量％、更优选不超过0.8重量％、更优选不超过0.75重量％、更优选不超过0.5重量％。由于AA对于婴儿获得最佳的膜功能特别是神经组织的膜功能至关重要，所以n-6 LC-PUFA的量优选至少为总脂肪酸的0.02重量％、更优选至少0.05重量％、更优选至少0.1重量％、更优选至少0.25重量％。本发明的组合物优选含有低于总脂肪酸1重量％的AA。AA在低LA组合物中的存在是有利的，因为AA补充LA的不足。AA的存在，优选少量AA的存在，对于低于6月龄婴儿的给药在营养上是有利的，因为对于这些婴儿而言，婴儿配方通常是唯一的营养来源。
本发明的婴儿营养剂优选n-6 LC-PUFA/n-3 LC-PUFA的重量比例较低以预防以后的生命中罹患肥胖症。优选所述组合物含有n-6 LC-PUFA/n-3LC-PUFA的重量比低于1.5、更优选低于1.0、更优选低于0.6。
LA、ALA、MCFA和/或LC-PUFA优选以游离脂肪酸、甘油三酯形式、甘油二酯形式、单酸甘油酯形式、磷脂形式、或上述中的一种或多种的混合物的形式提供。优选本发明的组合物含有甘油三酯和/或磷脂形式的LC-PUFA、更优选磷脂形式，因为磷脂形式的LC-PUFA更好地进入膜中。优选本发明的组合物包含甘油三酯形式的MCFA。
优选本发明的组合物包含至少一种、优选至少两种选自于亚麻籽油、油菜籽油(包括菜籽油、低芥酸油菜籽油和芥花籽油(canola oil))、鼠尾草油(salvia oil)、紫苏油、马齿苋油、越橘油、沙棘油、大麻油、高油酸葵花籽油、高油酸红花油、橄榄油、海产油、微生物油、黑醋栗籽油、蓝蓟油、黄油脂、椰油和棕榈仁油的脂质源。优选本发明的组合物包含至少一种、优选至少两种选自于亚麻籽油、油菜籽油、椰油、高油酸葵花油、黄油和海产油的脂质来源。
表1  给出了本发明组合物脂质组分的优选特征
表1
 
优选 更优选 最优选
LA(占总脂肪酸的重量％) <15 5-14.5 6-12
ALA(占总脂肪酸的重量％) >1 1.6-10 2.0-5.0
LA/ALA重量比例 2-7 3-6 4-5.5
MCFA(占总脂肪酸的重量％) 3-50 10-40 15-25
N-6 LC-PUFA(占总脂肪酸的重量％，AA+DHGLA总和) 0.02-0.8 0.05-0.75 0.25-0.5
n-3LC-PUFA(占总脂肪酸的重量％，EPA、DPA和DHA的总和) >0.2 0.25-15 0.75-5
n-6LC-PUFA/n-3LC-PUFA比例 <1.5 <1.0 <0.6
磷脂、胆固醇和鞘脂
由于LA是必需脂肪酸，且n-6 LC-PUFA是重要的膜组分(包括在神经组织膜中)，因此本发明组合物中低水平的LA和任选存在的n-6 LC-PUFA优选尽可能高效地进入神经细胞膜中。通过向本发明的低LA组合物提供脂质膜组分包括胆固醇、磷脂和/或鞘磷脂可以达到这一目的。这些组分的存在促进PUFA包括LA和n-6 LC-PUFA进入膜内，从而防止氧化。
本发明中使用的术语磷脂具体是指甘油磷脂。甘油磷脂作为一类脂质，由与甘油基团骨架的1位碳和2位碳上的羟基发生酯化的脂肪酸和与甘油的3位碳通过酯键连接的带负电的磷酸基团以及任选的与该磷酸基团连接的胆碱基团(在磷脂酰胆碱的情况下)、丝氨酸基团(在磷脂酰丝氨酸的情况下)、乙醇胺基团(在磷脂酰乙醇胺的情况下)、肌醇基团(在磷脂酰肌醇的情况下)或甘油基团(在磷脂酰甘油的情况下)形成。优选本发明的组合物含有磷脂酰胆碱(PC)、磷脂酰丝氨酸、磷脂酰肌醇和/或磷脂酰乙醇胺，更优选至少含有磷脂酰胆碱。
优选的磷脂源特别是PC源是大豆卵磷脂、卵脂质和/或酪乳脂肪。因此本发明的组合物优选包含大豆卵磷脂、卵脂质和/或酪乳脂肪、更优选大豆卵磷脂和/或酪乳脂肪。
优选本发明的组合物含有的磷脂占总脂质的0.5至20重量％、更优选1至10重量％、更优选4至8重量％。本发明的发明人还发现，口服给药含有磷脂和/或鞘脂和/或胆固醇的组合物还有进一步的优势，就是降低餐后胰岛素反应(见实施例2)。高胰岛素水平刺激脂肪组织摄取葡萄糖，使脂肪组织量增加。在婴儿中，高胰岛素水平也导致内脏脂肪细胞增殖增加，这至少部分地归因于增加的葡萄糖摄取。因此，本发明旨在减少婴儿以后的生命中罹患肥胖症的发病的组合物优选包含磷脂、鞘脂和/或胆固醇，更优选磷脂。
优选本发明的组合物含有的鞘脂占总脂质的0.5-20重量％、优选1-10重量％、更优选4-8重量％。本发明中的术语鞘脂是指具有氨基醇鞘氨醇的糖脂。鞘氨醇骨架通过O与(通常)带电荷的首基例如乙醇胺、丝氨酸或胆碱骨架连接。该骨架还通过酰胺与脂肪酰基连接。鞘脂包括神经鞘磷脂、神经酰胺和糖鞘脂。优选本发明的组合物包含神经鞘磷脂和/或糖鞘脂。糖鞘脂是具有一个或多个糖残基的神经酰胺，所述糖残基在1-羟基位置上通过β-糖苷键连接。糖鞘脂可以进一步细分为脑苷脂、红细胞糖苷脂和神经节苷脂。脑苷脂在1-羟基位置上有一个葡萄糖或半乳糖，而神经节苷脂具有至少三个糖，其中一个必须是唾液酸。神经鞘磷脂具有与神经酰胺的1-羟基发生酯化的磷酰胆碱或磷乙醇胺分子。优选本发明的组合物包含神经节苷脂。
优选所述组合物包含鞘脂，更优选神经鞘磷脂和/或神经节苷脂。优选本发明的组合物包含至少一种选自于GM3和GD3的神经节苷脂。
优选本发明的组合物含有的(神经鞘脂和磷脂的总量)占总脂质的0.5-20重量％、优选1-10重量％、更优选4-8重量％。
膳食胆固醇通过刺激脂肪酰基链(磷脂、游离脂肪酸；甘油二酯和甘油三酯)的链延长来调节脂质代谢。通过影响必需脂肪酸向其后继产物LC-PUFA的转化，膜必需的结构单元的生成得以增加，因此脑中神经元膜的合成和功能也增加。结果是必需脂质用于能量代谢的利用减少了。此外，胆固醇是膜的必需结构单元，而且对增加膜合成是必要的。因此本发明的低LA组合物中有利地包含胆固醇以预防本发明的配方中低水平LA带来的副作用。
此外，婴儿期内的膳食胆固醇抑制内源性胆固醇的合成，并使内源性胆固醇的合成程序性地调节为较低水平。从而在以后的生命中会得到降低的血胆固醇水平。这使青春期和成年期血中的LDL胆固醇值下降，HDL胆固醇值上升。因此本发明还提供包含脂质、蛋白质、可消化碳水化合物和胆固醇的组合物用于制备给药于年龄低于36个月的婴儿以预防其在以后的生命中罹患心血管疾病、动脉粥样硬化和/或血中胆固醇水平过高的营养组合物的用途。该营养组合物优选具有本申请中描述的营养要求的至少一部分，例如有利地包含本文描述的不可消化的寡糖、乳糖和/或脂质组分。
优选的胆固醇源是乳脂、酪乳脂肪、奶油乳清脂肪(butterserum fat)和卵脂质。因此本发明的组合物优选包含酪乳脂肪、奶油乳清脂肪和/或卵脂质。本发明的组合物优选包含至少占总脂肪0.005重量％、更优选至少0.01重量％、更优选至少0.05重量％、更优选至少0.1重量％的胆固醇。优选胆固醇的量不超过总脂质的10重量％、更优选不超过5重量％、更优选不超过1重量％。最优选胆固醇量为总脂质的0.5-0.7重量％。
优选胆固醇的量不超过总脂肪的1重量％、更优选不超过0.5重量％。
尿苷和胆碱
或者，本发明的低LA组合物包含尿苷和胆碱源。在接受本发明的低LA组合物的人类中，优选通过提供磷脂酰胆碱或其它脑中的主要膜磷脂的两种主要前体即尿苷和胆碱源来加强膜的合成。尿苷被代谢为胞苷，随后被磷酸化为CTP；胆碱被代谢为磷酸胆碱。然后CTP和磷酸胆碱形成CDP-胆碱，这在磷脂生物合成途径中是关键的一步。因此，尿苷和胆碱源的组合刺激磷脂的生物合成。通过添加尿苷和胆碱导致的磷脂合成的增强，也增强花生四烯酸和其它LC-PUFA进入脑中的主要磷脂，这使之特别适合于抵消本发明的低LA组合物的副作用。
优选所述组合物包含尿苷和胆碱源。胆碱优选以氯化胆碱的形式加入。本发明的组合物优选含有氯化胆碱。本发明的组合物优选含有占组合物干重至少0.035重量％、更优选至少0.045重量％的胆碱。优选本发明的组合物含有不高于本发明组合物总干重的1重量％、更优选低于0.5重量％、更优选低于0.1重量％的胆碱。胆碱存在的另一优势是胆碱氧化脂肪，导致增加瘦体重并促进血中脂肪向细胞中清除。胆碱的另一优势是它是优秀的甲基供体。在快速生长期例如婴儿期内，足量的甲基供体对于维持分化和调控都非常重要，从而通过DNA甲基化作用形成正确的代谢印迹。正确的代谢印迹对于预防以后的生命中罹患肥胖症是重要的。因此本发明的组合物优选含有胆碱。
在优选的实施方案中，本发明的组合物含有核苷酸、核苷和/或碱基形式的尿苷。优选所述组合物含有本发明组合物干重的0.001-0.1重量％、更优选0.002-0.05重量％、最优选0.002-0.025重量％的尿苷。更优选所述组合物含有核苷酸形式的尿苷。尿苷优选是一磷酸核苷酸、二磷酸核苷酸或三磷酸核苷酸形式、更优选一磷酸核苷酸形式。尿苷核苷酸可以是单体、二聚体或多聚体(包括RNA)。所述核苷酸优选作为游离酸或盐的形式存在、更优选一钠盐的形式。优选本发明的组合物包含尿苷5’-一磷酸和/或其盐(一起缩写为UMP)，特别是其一钠盐。优选组合物包含占所述本发明组合物干重0.001-0.1重量％、更优选0.002-0.05重量％、最优选0.002-0.025重量％的UMP。UMP优选在核苷酸的混合物中加入所述组合物中。
优选本发明的组合物含有酵母RNA作为UMP源。优选本发明组合物包含UMP和胆碱。优选所述组合物包含尿苷、胆碱和磷脂源。优选所述组合物包含UMP、胆碱和磷脂。该组合进一步刺激膜的形成，因此特别适合于包含在本发明的低LA组合物中。
不可消化的寡糖
如上所述，高血胰岛素水平刺激脂肪组织对葡萄糖的摄取，导致脂肪组织量增加。在婴儿中，高胰岛素水平有助于脂肪细胞增殖增加，至少部分是由于增加的葡萄糖摄入，从而增加了以后生命中罹患肥胖症的风险。
因此本发明组合物优选保持较低的胰岛素水平。发现可发酵的不可消化的寡糖(NDO)(特别是半乳寡糖)具有缓和血中胰岛素水平的作用，因而有助于降低以后生命中罹患肥胖症的风险。
此外还认识到人工喂养的婴儿比母乳喂养的婴儿摄入的热量更高。除了本发明建议的脂质组分的组成特征之外，可通过降低卡路里摄入量进一步提高有效性。但是限制营养组合物的剂量对婴儿是不可行的选择。本发明的发明人发现，为此目的本发明的组合物有利地含有不可消化的寡糖。
这些不可消化的寡糖、优选半乳寡糖的发酵进一步导致肠道乙酸酯的形成，乙酸酯被摄取并进入循环和肝脏中，从而有利地作为脂质延长前体和/或有利地刺激LA向AA的转化。
因此，本发明的组合物优选包含本发明的脂质组分和可发酵的不可消化的寡糖。本发明脂质组分与不可消化的寡糖的组合协同地减少以后生命中肥胖症的发病。优选本发明的组合物包含的不可消化的寡糖的聚合度为2-60。所述组合物优选预防胰岛素抵抗的发病。不可消化的寡糖优选选自于果寡糖(包括菊糖)、半乳寡糖(包括反式半乳寡糖)、葡糖寡糖(包括龙胆寡糖、黑曲霉寡糖和环糊精寡糖)、阿拉伯寡糖、甘露寡糖、木寡糖、岩藻寡糖、阿拉伯半乳寡糖、葡糖甘露寡糖、半乳甘露寡糖、含有唾液酸的寡糖和糖醛酸寡糖。优选本发明的组合物包含果寡糖、半乳寡糖和/或半乳糖醛酸寡糖、更优选半乳寡糖、最优选反式半乳寡糖。在优选的实施方案中，所述组合物包含反式半乳寡糖和果寡糖的混合物。优选本发明的组合物含有聚合度为2-10的半乳寡糖和/或聚合度为2-60的果寡糖。半乳寡糖优选选自于反式半乳寡糖、乳糖-N-四糖(LNT)、乳糖-N-新四糖(新-LNT)、岩藻糖基乳糖(fucosyl-lactose)、岩藻糖基化LNT(fucosylated LNT)和岩藻糖基化新-LNT(fucosylated neo-LNT)。在特别优选的实施方案中，本发明的方法包括给药反式半乳寡糖([半乳糖]n-葡萄糖；其中n是1-60的整数，即2、3、4、5、6、....、59、60；优选n选自于2、3、4、5、6、7、8、9或10)。反式半乳寡糖(TOS)以例如商标名VivinalTM销售(Borculo DomoIngredients，Netherlands)。优选反式半乳寡糖的糖是β-连接的。果寡糖是包含β连接的果糖单元链的NDO，聚合度或平均聚合度为2-250、更优选10-100。果寡糖包括菊糖、果聚糖和/或混合类型的多聚果糖。特别优选的果寡糖是菊糖。适用于本发明组合物的果寡糖也是可商购获得的，例如Raftiline
Figure A200680053302D0016171924QIETU
 HP(Orafti)。糖醛酸寡糖优选从果胶降解中获得。因此本发明的组合物优选包含果胶降解产物，其聚合度为2-100。优选果胶降解产物从苹果果胶、甜菜果胶和/或柑橘果胶制备。优选本发明的组合物包含反式半乳寡糖、果寡糖和果胶降解产物。反式半乳寡糖：果寡糖：果胶降解产物的重量比例优选为20-2:1:1-3、更优选12-7:1:1-2。
乳糖
胰岛素敏感度的维持能够通过在本发明组合物中包含低升糖的碳水化合物优选乳糖得到进一步改善。因此本发明的组合物除了本发明的脂质组分之外还优选包含不可消化的寡糖和/或乳糖。本发明的组合物优选包含可消化碳水化合物组分，其中至少35重量％、更优选至少50重量％、更优选至少75重量％、更优选至少90重量％、最优选至少95重量％是乳糖。每100mg干重的本发明组合物优选含有至少25g乳糖、优选至少40g乳糖/100g。
水解蛋白
本发明的组合物优选包含水解酪蛋白和/或水解乳清蛋白。发现与给药含有完整酪蛋白和完整乳清蛋白的组合物相比，给药其中蛋白质包含水解酪蛋白和水解乳清蛋白的组合物，餐后胰岛素水平和葡萄糖水平都降低。胰岛素和葡萄糖水平都升高表明在用配方喂养的婴儿中有某种形式的胰岛素抵抗，据信这导致以后的生命中罹患肥胖症。本发明的组合物优选含有占蛋白质干重至少25重量％的链长为2至30个氨基酸的肽。链长为2-30的肽的量可以根据例如de Freitas等，1993，J.Agric.Food Chem.41:1432-1438中所述测定。本发明的组合物优选含有酪蛋白水解物和/或乳清蛋白水解物、更优选酪蛋白水解物和乳清蛋白水解物，因为牛酪蛋白的氨基酸组成更接近于人乳蛋白质的氨基酸组成，且乳清蛋白更容易消化，并且在人乳中比例较高。本发明组合物优选含有占蛋白质总重至少50重量％、优选至少80重量％、最优选约100重量％的蛋白质水解物。本发明组合物优选包含蛋白质水解度为5-25％、更优选7.5-21％、最优选10-20％的蛋白质。水解度的定义为被酶水解作用裂解的肽键的百分比，存在的潜在肽键总数为100％。
酪蛋白
酪蛋白的存在有利，因为其通过在胃中形成凝乳来增加胃排空时间，从而增强饱满感。因为高度期望诱导出现饱满感，如上所述，因此本发明的组合物优选包含酪蛋白。当组合物是液体形式例如即开即饮的液体时，每100ml所述组合物优选包含至少0.5g、优选0.5-5g的酪蛋白。优选该组合物以干重计含有至少4重量％的酪蛋白。优选酪蛋白为完整蛋白和/或非水解形式。
钙
优选本发明的组合物含有钙。膳食钙的增加降低脂肪细胞内钙浓度，这可能减少脂肪细胞的晚期分化和脂质填充。优选钙与作为反荷阴离子的碳酸根、氢氧根、氯离子、磷酸根、乳酸根、葡糖酸根和/或柠檬酸根一起加入。优选所述组合物包含占组合物干重至少0.1重量％、优选至少0.25重量％、最优选至少0.4重量％的钙。优选所述组合物包含低于组合物干重的5重量％、优选低于2重量％、更优选低于1重量％的钙。
营养组合物
本发明的组合物特别适合于为年龄低于36个月、特别是低于24个月、更优选低于18个月、最优选低于12个月的婴儿提供每日营养需求。因此本发明的组合物包含脂质、蛋白质和可消化碳水化合物组分，其中脂质组分提供总热量的35-55％，蛋白质组分提供总热量的5-15％，可消化碳水化合物提供总热量的30-60％。优选本发明的组合物包含的脂质组分提供总热量的40-50％，蛋白质组分提供总热量的6-12％，可消化碳水化合物提供总热量的40-50％。当组合物是液体形式例如即开即饮的液体时，每100ml组合物优选包含2.1-6.5g、更优选3.0-4.0g的脂质。基于干重，本发明的组合物优选含有12.5-40重量％、更优选19-30重量％的脂质。
饱和脂肪酸的量优选低于总脂肪酸的58重量％、更优选低于45重量％。单不饱和脂肪酸的浓度优选占脂肪酸总重的17-60％。
本发明的组合物不是人类母乳。本发明的组合物优选包含(i)植物脂质和/或动物(非人类)脂肪；和/或(ii)植物蛋白质和/或动物(非人类)奶乳蛋白质。动物奶乳蛋白质的实例有牛奶乳清蛋白和山羊奶蛋白。本发明的组合物优选不包含蛋白酶抑制剂，优选不包含胰蛋白酶抑制剂、糜蛋白酶抑制剂或弹性蛋白酶抑制剂。本发明的组合不是人乳。
本发明的组合物的总蛋白质中优选含有至少50重量％、更优选至少90重量％的得自非人乳的蛋白质。优选本发明的组合物的总蛋白质中包含至少50重量％、优选至少90重量％的得自牛乳的蛋白质。优选本发明的组合物包含具有较低浓度的糖巨肽的酸乳清和/或甜乳清。优选本发明的组合物包含得自β-酪蛋白和/或α-乳清蛋白的蛋白质。本发明的组合物优选含有酪蛋白和乳清蛋白，二者重量比例为酪蛋白：乳清蛋白10:90至90:10、更优选20:80至80:20。本发明使用的术语蛋白质是指蛋白质、肽和游离氨基酸的总和。本发明的组合物优选含有1.5-3.0g蛋白质/100kcal、优选1.8-2.25g/100kcal、更优选1.8-2.0g/100kcal。
本发明的组合物优选以液体形式给药。为满足婴儿的热量需求，所述组合物优选含有50至200kcal/100ml液体、更优选60至90kcal/100ml液体、更优选60至75kcal/100ml液体。这种热量密度保证摄入的水与热量具有最佳比例。本发明组合物的重量克分子渗透浓度优选为150-420mOsmol/l、更优选260至320mOsmol/l。低重量克分子渗透浓度的目的是降低胃肠道应激。应激可诱发肥胖症。
优选本发明组合物为液体形式，用Brookfield粘度计在20℃下、切变率为100s-1的条件下测量的粘度低于35cps。适当地，本发明组合物可以是粉末形式，其可重新溶解于水中形成液体，或者是液体浓缩物的形式，其应该用水稀释。
当本发明组合物为液体形式时，优选的每日给药体积为约80至2500ml、更优选每日约450至1000ml。
婴儿
脂肪细胞(包括内脏脂肪细胞)在生命的前36个月增殖，在青春期也增殖(更有限)。脂肪细胞的数量是以后生命中肥胖程度的重要决定因素。因此本发明的组合物在婴儿生命的前3年给药。发现在生命的前12个月(具有围产期脂肪细胞增殖的最佳条件)出现(内脏)脂肪细胞显著增殖。因此特别优选本发明的组合物在婴儿的这一生命阶段给药。因此本发明的组合物优选给药于0-24月龄、更优选0-18月龄、最优选0-12月龄的人类。本发明的目的特别在于预防以后生命中罹患肥胖症，优选不是用于治疗肥胖症。因此本发明的组合物优选给药于没有罹患肥胖症或儿童肥胖症的婴儿，特别是非肥胖婴儿、更优选不超重的婴儿。本发明的组合物优选口服给药于婴儿。
应用
本发明的组合物涉及在低于36月龄的人类中预防肥胖症的方法。本发明还旨在预防年龄高于36个月、特别是年龄高于8岁、特别是年龄高于15岁、更特别是年龄高于18岁的人类罹患肥胖症。
优选本发明组合物用于预防肥胖症、更优选向心性肥胖(即肥胖症)，因为向心性肥胖格外地与诸如心血管疾病、高血压和糖尿病等病症有关。
在本文及其权利要求书中，动词“包含”或“含有”及其各种变化形式具有非限制性的意义，意在包括其后的各项，但并不排除没有具体提及的各项。此外，提及元素时使用的不定冠词“a”或“an”不排除多于一个该元素存在的可能性，除非上下文明确要求有且仅有一个该元素。不定冠词“a”或“an”因此通常是指“至少一个”。
实施例
实施例1：膳食脂质对成体脂肪组织的程序性调节作用
将C57/BL6雌鼠的后代在出生后第二天进行标准化，分为每巢6只幼鼠(4只雄性和2只雌性)。从第二天开始用实验饮食饲喂母鼠直至断奶。小鼠奶乳的脂质组成反应了饮食的脂肪组成。断奶后将雄性小鼠每两只一起饲养，持续用实验饮食喂养直至第42天，此时所有的小鼠都用含有猪油和额外胆固醇(1％)的相同饮食饲养。
使用的实验饮食有：1)LC-PUFA饮食(金枪鱼油)；2)低LA、低LA/ALA饮食(黄油；芥花籽油含量低、Trisun80含量高、无棕榈油)；3)MCFA饮食；4)对照饮食(相似量的芥花籽油、椰油和棕榈油)。饮食的脂肪酸组成见表2。第42天，将所有小鼠的饮食都转为“自助饮食(cafeteria diet)”，其含有10重量％的脂质(3重量％的猪油脂肪和1重量％的胆固醇)，直至第98天。每周将小鼠称重两次。整个实验过程中每周一次测量食物摄入量。为测量身体组成(即脂肪量(FM)和非脂肪量(FFM))，在6、10和14周龄，分别是出生后42、70和98日龄时在全麻条件下进行DEXA扫描(双能X射线吸收仪)，使用PIXImus成像仪(GE Lunar，Madison，WI，USA)根据光密度法测定。在14周龄时，将雄性小鼠处死，取血浆、附睾脂肪、肾脂肪、胰、肝和肾并称重。
表2:饮食中的脂肪酸组成
 
对照 MCFA LC-PUFA Low LA 自助
g/100g脂肪 g/100g脂肪 g/100g脂肪 g/100g脂肪 g/100g脂肪
C-4:0 0.00 0.00 0.00 1.05 0.00
C-6:0 0.11 0.15 0.07 0.81 0.06
C-8:0 1.70 11.42 1.07 2.09 0.85
C-10:0 1.36 8.77 0.86 2.17 0.68
C-12:0 10.53 1.34 6.69 11.42 5.27
C-14:0 4.38 0.75 3.62 7.24 2.69
C-14:1w5 0.00 0.00 0.00 0.00 0.00
C-15:0 0.00 0.00 0.00 0.00 0.00
C-16:0 17.14 13.35 19.38 12.40 23.07
C-16:1w7 0.13 0.12 1.20 0.78 1.56
C-17:0 0.00 0.00 0.37 0.00 0.00
C-18:0 3.07 2.39 3.70 5.12 9.03
C-18:1w9 37.94 38.52 35.27 40.79 40.47
C-18:2w6 LA 14.80 14.31 11.89 6.38 11.90
C-18:3w3 ALA 2.61 2.61 1.07 1.57 1.30
C-18:3w6 0.00 0.00 0.00 0.00 0.00
C-18:4w3 0.00 0.00 0.19 0.00 0.00
C-20:0 0.34 0.34 0.26 0.20 0.17
C-20:1w9 0.41 0.41 0.15 0.22 0.21
C-20:2w6 0.00 0.00 0.00 0.00 0.00
C-20:3w6 0.00 0.00 0.00 0.00 0.00
C-20:4w3 0.00 0.00 0.07 0.00 0.00
 
C-20:4w6 AA 0.00 0.00 0.28 0.00 0.00
C-20:5w3 EPA 0.00 0.00 1.20 0.00 0.00
C-22:0 0.23 0.28 0.24 0.33 0.11
C-22:1w9 0.14 0.14 0.05 0.08 0.07
C-22:4w6 0.00 0.00 0.00 0.00 0.00
C-22:5w3 DPA 0.00 0.00 0.37 0.00 0.00
C-22:6w3 DHA 0.00 0.00 5.00 0.00 0.00
C-24:0 0.02 0.02 0.02 0.00 0.01
C-24:1w9 0.00 0.00 0.00 0.00 0.00
胆固醇 1.00
总计 94.91 94.92 93.02 92.66 98.46
结果：在实验期间，未观察到对各组间生长和食物摄入量有影响(数据未显示)。而且，脂肪量的形成(由DEXA测定)在第42天(饮食介入期末)没有差异。但是，随后在第42天至98天之间使所有各组饲喂自助饮食(饱和脂肪酸含量高)，在实验结束(第98天)时各组身体组成有明显差异，见表3。与对照饮食相比，在生命早期进食LC-PUFA、MCFA或低LA低LA/ALA饮食的幼仔的脂肪量下降。而且，生命早期饮食对身体脂肪分布有显著影响。与对照组相比，第98天成年小鼠的皮下脂肪：内脏脂肪(分别由附睾脂肪和肾脂肪测量)在LC-PUFA组中增长14％，在低LA组中增长32％，但在MCFA组中没有增加，见表3。这表明生命早期进食高LC-PUFA含量和/或低LA和/或低LA/ALA的饮食明显降低了以后生命中的内脏脂肪量。因此，结论是这些脂肪组成对身体进行规划和/或使身体留下印迹，使身体在以后的生命中获得更加健康的身体脂肪组成。因此，结论是这些脂肪组成对身体进行规划和/或印迹以预防以后生命中罹患肥胖症。
表3：各时间总体重中形成的脂肪％以及皮下(附睾)脂肪与向心(肾)脂肪的比例
 
天 对照饮食 MCFA饮食 LC-PUFA饮食 Low LA饮食
脂肪量(％) 42 19.6 17.1 16.6 17.1
脂肪量(％) 70 22.1 22.8 21.5 24.2
脂肪量(％) 98 26.9 22.8 20.9 24.2
皮下脂肪/内脏脂肪的比例 98 7.54 7.2 8.59 9.92
比例增幅(％) -4％ +14％ +32％
实施例2：磷脂有益地影响胰岛素敏感度
营养组合物：使用可商购获得的Lactalis的酪乳/奶油乳清(butterserum)浓缩物作为来源制备额外加入磷脂(0.2g/100ml)的完全婴儿配方。具有类似组成但不加入磷脂的婴儿配方作为对照。磷脂浓度占实验配方总脂质的约6.3重量％，占对照配方总脂质的约0.75重量％。实验组合物中含有约占总脂质1.4重量％的神经鞘磷脂，约4重量％的胆固醇。神经鞘磷脂和胆固醇在对照配方中可忽略不计。
方法：将20只成年Wistar大鼠(实验开始时10周龄)单独饲养。4小时禁食期后，向10只动物饲喂2ml的组合物。三种不同的组合物在交叉实验设计中进行试验(实验相隔1周)：i)标准婴儿配方，ii)含有磷脂的配方。然后，在肝素化预冷的试管中收集血样，时间为饲喂后t＝0、5、10、15、30、60分钟。然后，离心(10min，5000rpm)分离血浆并储存在-20℃直至分析。通过放射免疫测定法(RIA，Linco Research)，根据制造商说明书并进行以下调整，测定血浆中胰岛素：全部测定体积减少4倍。
结果：用含磷脂配方饲喂的大鼠胰岛素曲线下面积(AUC)低于用标准配方饲喂的动物(表4)。喂食含有磷脂、鞘脂和/或胆固醇的配方得到的餐后胰岛素水平和动力学与之前的观察到的用人乳喂食的结果相似。胰岛素水平的下降表明胰岛素敏感度的升高，据信胰岛素敏感度升高有助于预防以后的生命中罹患肥胖特别是向心性肥胖。
表4：磷脂对餐后胰岛素曲线下面积的影响
Figure A200680053302D00241
实施例3：血中葡萄糖/胰岛素和不可消化的寡糖
动物和处理：第1天，通过胃管给予成年雄性Wistar大鼠(n＝7)GOS纤维负荷、纤维素负荷或水。给予等于它们每日纤维摄入量50％的6ml推注负荷；使用的GOS纤维是反式半乳寡糖，得自Elix’or(Borculo Domo)。将纤维溶于水中。约24小时后(第2天)，进行口服葡萄糖耐量试验，在胃内注射碳水化合物负荷(2g/kg体重)后检测120分钟内餐后葡萄糖和胰岛素时程。为此，通过颈静脉插管反复抽取血样。在第1天胃内注射水或纤维素水溶液作为对照。由于GOS纤维制剂含有50％的可消化碳水化合物(主要是乳糖)，因此两个对照注射与碳水化合物共同给药以对此进行校正。
结果：用GOS纤维预先处理明显地降低了胰岛素分泌量，导致显著降低的AUC增幅(p<0.05)。血中葡萄糖水平未受显著影响。用纤维素或水预先处理没有调节胰岛素分泌，见表5。
表5：大鼠中胰岛素和葡萄糖水平
 
预处理 AUC胰岛素(pM*30min) AUC葡萄糖(mM*30min)
水 41±7 69±10
纤维素 46±8 75±9
GOS 22±4 74±15
实施例4：婴儿营养剂
婴儿营养剂中含有提供总热量的48％的脂质组分、提供总热量的8％的蛋白质组分，提供总热量的44％的可消化碳水化合物；(i)脂质组分中含有的物质及其占总脂肪酸的量：14重量％LA；2.6重量％ALA、3.7重量％MCFA；0.2重量％DHA、0.05重量％EPA；0.02重量％DPA、0.35重量％AA、0.03重量％DHGLA。基于组总脂肪，组合物含有约0.75重量％的大豆磷脂和>0.005重量％的胆固醇。(ii)碳水化合物组分包含50.9g乳糖/100g粉末；5.22g聚合度为2-6的半乳寡糖和0.58g聚合度为7-60的果寡糖；(ii)蛋白质组分包含牛奶蛋白，包括酪蛋白。此外，每100g干重的组合物包含73mg胆碱和5.6mg UMP。每100g干重的组合物含有364mg钙。根据欧盟指导原则，组合物包含维生素和矿物质。该婴儿营养剂的包装标签标明该营养剂预防罹患肥胖症。

Claims (16)

1.含有脂质、蛋白质和可消化碳水化合物组分的组合物用于制备给药于年龄低于36个月的非肥胖婴儿以预防肥胖症的营养组合物的用途，其中所述脂质组分包含：
(i)亚油酸(LA)和α-亚麻酸(ALA)，其重量比例LA/ALA为2-7；
(ii)低于总脂肪酸的15重量％的LA，和
(iii)至少为总脂肪酸的1重量％的ALA；
且其中所述组合物进一步包含至少一种选自于下组的组分：
(a)占总脂肪0.5-20重量％的磷脂；
(b)占总脂肪0.5-20重量％的鞘脂；
(c)占总脂肪0.005-10重量％的胆固醇；和
(d)占所述组合物干重0.035-1重量％的胆碱和占所述组合物干重0.001-0.1重量％的尿苷。
2.权利要求1的用途，其中所述组合物含有胆碱、尿苷源和磷脂。
3.前述权利要求之任一项的用途，其中所述尿苷源是尿苷—磷酸。
4.前述权利要求之任一项的用途，其是用于预防以后生命中罹患肥胖症和/或用于预防所述婴儿年龄高于36个月时罹患肥胖症的用途。
5.前述权利要求之任一项的用途，其中所述组合物进一步包含：
(i)占总脂肪酸3-50重量％的中链脂肪酸(MCFA)；和/或
(ii)n-6长链多不饱和脂肪酸(LC-PUFA)和n-3LC-PUFA，其重量比例低于1.5，n-6LC-PUFA占总脂肪酸的0.02-0.8重量％，n-3LC-PUFA占总脂肪酸的至少0.2重量％。
6.前述权利要求之任一项的用途，其中所述脂质组分提供总热量的35-55％，所述蛋白质组分提供总热量的5-15％，所述可消化碳水化合物组分提供总热量的30-60％。
7.前述权利要求之任一项的用途，其中所述组合物提供60-90kcal/100ml。
8.前述权利要求之任一项的用途，其是用于预防所述人类年龄高于12岁时罹患肥胖症的用途。
9.前述权利要求之任一项的用途，其中所述营养组合物给药于年龄低于12个月的婴儿。
10.前述权利要求之任一项的用途，其中所述组合物进一步包含占所述组合物干重至少0.5重量％的至少一种可溶性、不可消化的寡糖。
11.前述权利要求之任一项的用途，其中所述组合物含有至少0.5重量％的至少一种可溶性、不可消化的寡糖，其选自于果寡糖(包括菊糖)、半乳寡糖(包括反式半乳寡糖)、葡糖寡糖(包括龙胆寡糖、黑曲霉寡糖和环糊精寡糖)、阿拉伯寡糖、甘露寡糖、木寡糖、岩藻寡糖、阿拉伯半乳寡糖、葡糖甘露寡糖、半乳甘露寡糖、含有唾液酸的寡糖和糖醛酸寡糖。
12.前述权利要求之任一项的用途，其中所述组合物含有半乳寡糖。
13.前述权利要求之任一项的用途，其中所述组合物还含有果寡糖。
14.前述权利要求之任一项的用途，其中所述组合物含有占所述组合物干重至少0.3重量％的钙。
15.前述权利要求之任一项的用途，其中所述给药于年龄低于36个月的婴儿的营养组合物用于预防其以后生命中罹患心血管疾病、动脉粥样硬化和/或血中胆固醇水平过高。
16.含有脂质、蛋白质、可消化碳水化合物和胆固醇的组合物用于制备给药于年龄低于36个月的婴儿以预防其以后生命中罹患心血管疾病、动脉粥样硬化和/或血中胆固醇水平过高的营养组合物的用途。
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US20090156487A1 (en) 2009-06-18
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