CN105899218A - 对孕产妇施用维生素b12预防后代尤其是超重和/或肥胖母亲的后代发胖、超重或肥胖的增加 - Google Patents
对孕产妇施用维生素b12预防后代尤其是超重和/或肥胖母亲的后代发胖、超重或肥胖的增加 Download PDFInfo
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Abstract
本发明整体涉及婴幼儿超重、肥胖、过量脂肪积聚和/或相关代谢紊乱的早期预防。例如,本发明涉及通过对希望怀孕和/或孕期和/或哺乳期的妇女施用适当的营养来预防婴幼儿发生超重、肥胖、过量脂肪积聚和/或相关代谢紊乱。本发明的实施方案涉及用于预防后代发生超重、肥胖、过量脂肪积聚和/或相关代谢紊乱的维生素B12的用途,其中将所述维生素B12施用于希望怀孕的超重和/或肥胖妇女,以及/或者孕期和/或哺乳期的超重和/或肥胖母亲,并且涉及可用于此目的的孕产妇食物组合物。
Description
本发明整体涉及婴幼儿超重、肥胖、过量脂肪积聚和/或相关代谢紊乱的早期预防。例如,本发明涉及通过在孕前、孕期和/或哺乳期施用适当的孕产妇营养来预防婴幼儿超重、肥胖、过量脂肪积聚和/或相关代谢紊乱。本发明的实施方案涉及用于预防后代超重、肥胖、过量脂肪积聚和/或相关代谢紊乱的维生素B12的用途,其中将所述维生素B12在孕前、孕期和/或哺乳期施用于超重和/或肥胖母亲,本发明的实施方案还涉及可用于此目的的孕产妇食物组合物。
背景技术
越来越多的科学证据显示,产前和产后的早期营养和其他环境因素会影响长期健康和良好状态的调控,并且可引起慢性疾病发展的风险。有几项研究表明,在生育期饮食摄入发生变化或对各种大量和微量营养素加以控制,可影响几种生理过程,例如生长、代谢、食欲、心血管功能等(Koletzko B et al(2011)Am J Nutr 94(s):2036-43S(Koletzko B等人,2011年,《美国营养学杂志》,第94期增刊,第2036-2043页))。因此,妇女在孕前和孕期的营养状态(营养物质储备和饮食摄入)与优化新生儿和儿童健康结果相关。据信孕产妇营养会影响营养物质对发育中的胎儿的有效性和供应,这些营养物质是关键发育过程中所需的。
儿童期超重和肥胖是许多国家(包括中等收入和低收入国家)面临的主要公共健康问题,近三十年的报告显示超重率和肥胖率日益增加。2008年,英国2至15岁儿童中就有约30%的儿童超重或肥胖。有证据表明,儿童5岁时的体重是儿童未来健康和良好状态的一个良好指标(Gardner et al(2009)Pediatrics 123:e67-73(Gardner等人,2009年,《儿科学》,第123卷,第e67-73页))。相关研究表明,儿童期肥胖会增加成人期患上肥胖和其他非常不利的慢性病症(例如心血管疾病、2型糖尿病、肝并发症、肾并发症和肌肉骨骼并发症等)的风险。有力证据表明,肥胖一旦形成,将很难通过干预逆转,肥胖将会一直持续到成人期(Waters E et al.(2011)Cochrane Database of Systematic Reviews 12(Waters E等人,2011年,《Cochrane系统评价数据库12》)),这凸显了儿童期肥胖预防工作的重要性。
一些可能的早期决定性因素(包括孕产妇肥胖和糖尿病、妊娠期过量增重、孕产妇吸烟、婴儿快速生长)与在以后的生活中发生超重和肥胖具有明显的相关性(Monasta L et al.(2010)Obesity Reviews.11:695-708(Monasta L等人,2010年,《肥胖综述》,第11卷,第695-708页))。虽然这种相关性对于这些因素中的每个因素而言不大,但如果某一小风险因素在人群中高度流行,那么当这些因素作用于该归因风险时,就可产生很大的作用。而且有些可能的决定性因素可能变得比其他因素更为重要,因为这些决定性因素更易于通过实施有效干预得以解决。
缺乏微量营养素对胎儿组织和器官具有深刻且通常持久的影响,即使母体并未表现缺乏这些微量营养素的临床征兆(Ashworth CJ et al(2001)122:527-35(Ashworth CJ等人,2001年,第122卷,第527-535页))。生活在资源匮乏环境中的生育期妇女普遍存在多种微量营养素的摄入不足(Torhem LE et al.(2010)J.Nutr.140:2051S–58S(Torhem LE等人,2010年,《营养学杂志》,第140卷增刊,第2051-2058页)),而且在一些环境中,由于不良饮食导致的与超重和肥胖相关的营养不良也开始受到关注。
本发明人调查了妇女中的微量营养素缺乏情况,以鉴定可用在产前和产后早期营养中来调控长期健康和良好状态的微量营养素,尤其是对降低慢性病(例如超重、肥胖、过量脂肪积聚和相关代谢紊乱(如糖尿病)、心血管疾病和高血压)发展风险有积极影响的微量营养素。
本说明书中对现有技术文献的任何提及不被视为承认此类现有技术为众所周知的技术或构成本领域普遍常识的一部分。
因此,希望为本领域提供一种解决方案,所述解决方案可以尽早在生命早期降低发展超重、肥胖、过量脂肪积聚和/或相关疾病的可能性。如果该解决方案可针对存在患上超重、肥胖、过量脂肪积聚和/或相关代谢紊乱的增加风险的受试对象,这将尤其有用。
因此,本发明的一个目的是提高现有技术水平,尤其是提供一种克服至少一些当前技术水平的缺点并满足上述需求的解决方案,或至少提供一种有用的替代方案。
发明内容
本发明涉及用于预防超重和/或肥胖母亲的后代超重、肥胖、过量脂肪积聚和/或相关代谢紊乱的维生素B12的用途。所述维生素B12将以多种形式被施用于希望怀孕的妇女以及/或者孕期和/或哺乳期的母亲。
具体实施方式
本发明人出乎意料地发现,他们可通过独立权利要求的主题实现这个目的。从属权利要求进一步拓展本发明的构想。
本发明人研究了表观遗传学作为早期营养效应的介体和标志在人类儿童期身体组成上的作用,还调查了人在以后的生活中发展肥胖和胰岛素抗性相关疾病的风险。本发明人在多组研究中进行了深入和详细的分析,他们惊奇地发现,超重和/或肥胖的孕妇比正常体重的母亲更缺乏维生素B12,这会导致超重和/或肥胖孕妇的后代发展超重、肥胖、过量脂肪积聚和/或相关代谢紊乱的可能性增加。
因此,本发明部分地涉及用于预防后代超重、肥胖、过量脂肪积聚和/或相关代谢紊乱的维生素B12的用途。
本发明还涉及维生素B12用于制备预防后代超重、肥胖、过量脂肪积聚和/或相关代谢紊乱的组合物的用途。所述用途可以是非治疗性用途。
本发明还涉及用于降低后代发展超重、肥胖、过量脂肪积聚和/或相关代谢紊乱的可能性的维生素B12的用途。
作为另一种选择,根据本文所述的本发明的任一实施方案,维生素B12或包含维生素B12的组合物用于预防或降低发展超重、肥胖、相关代谢紊乱和/或过量脂肪积聚的可能性。
可将所述维生素B12例如施用于孕前、孕期和/或哺乳期的母亲。所述母亲可以是超重和/或肥胖母亲,因为发现维生素B12补充剂对预防超重和/或肥胖母亲的后代发生超重、肥胖、过量脂肪积聚和/或相关代谢紊乱特别有效。
维生素B12补充剂对维生素B12水平较低和/或维生素B12摄入不足的母亲特别有效。
如果摄入的维生素B12低于建议饮食摄取量(RDA),则认为维生素B12摄入不足。RDA是指被认为足以满足每个生活阶段和每个性别群体中97.5%的健康个体的需求的每日饮食营养物质摄入水平。根据估计平均需要量(EAR)计算RDA,其中EAR基于科学文献综述预计可满足某一年龄群体中50%的个体的需要。
例如,如果孕妇每天摄入的维生素B12低于2.6μg,则可认为维生素B12摄入不足。
目前,维生素B12补充剂在本领域用于(例如)治疗氰化物中毒或钴胺传递蛋白II的遗传缺陷。
“超重”被定义为成人的BMI介于25和30之间。
“身体质量指数”或“BMI”是指体重(千克)除以身高(米)的平方所得的比值。
“肥胖”是指储存在动物(尤其是人和其他哺乳动物)脂肪组织中的天然能量储备增至与某些健康状况或死亡率上升有关的程度的一种病症。“肥胖”被定义为成人的BMI大于30。
就儿童来说,在BMI与年龄增长(女孩或男孩)关系的图表上绘制BMI,从而获得百分位排序。百分位是评估儿童个体的体型和生长模式最常用的指标。百分位指示了儿童BMI在相同性别和年龄的儿童中的相对位置。如果儿童BMI位于第85百分位和第95百分位之间,则认为该儿童超重。如果儿童BMI位于第95百分位或第95百分位以上,则认为该儿童肥胖。
与超重、肥胖和/或过量脂肪积聚有关的代谢紊乱是相似的,并且是技术人员熟知的。例如,这些疾病包括心血管疾病,如冠心病、胰岛素抗性、2型糖尿病、高血压、睡眠呼吸暂停、呼吸道疾病和/或血脂异常;而且还包括某些癌症(如子宫内膜癌、乳腺癌和/或结肠癌)、中风、肝脏和胆囊疾病、骨关节炎和/或妇科疾病。
由于可将维生素B12施用于孕期的孕妇和/或哺乳期的母亲,因此可以(例如)孕产妇食物组合物的形式来施用。
妇女在孕期和哺乳期的营养物质需求不断增加。如果增加的营养物质需求得到满足,那么可保护孕产妇和婴儿的健康。哺乳期要求孕产妇储备需要建立和补充的能量、蛋白质和其他营养物质。
孕产妇食物组合物是被设计用于帮助满足孕期和哺乳期妇女的特定营养需求的食物组合物。
例如,此类孕产妇食物组合物可包含蛋白质源、铁源、碘源、维生素A源和/或叶酸源。
孕产妇食物组合物可具有任何被母亲接受作为其饮食的部分或作为营养补充剂的形式。
例如,孕产妇食物组合物可选自粉状营养组合物(在奶或水中重构)、营养配方食品、基于谷类的产品、饮料、食品棒、营养补充剂、营养品、酸奶、乳制品、食物喷洒物(food sprinkler)、丸剂或片剂。
目前,特别被消费者广泛接受的是在奶或水中重构的粉状营养组合物。
另外,(例如)片剂形式的营养补充剂也被广泛接受。补充剂提供了选定的营养物质,但其在受试对象的整体营养需求中的占比不显著,并且/或者其在受试对象的每日能量需求中的占比不超过0.1%、1%、5%、10%或20%。
维生素B12可以任何能有效实现本发明目的的量使用。技术人员将能够确定合适的剂量。通常,剂量将取决于母亲的年龄、体型、健康状态、生活方式和基因遗传。
在本发明的预防应用中,维生素B12的施用量足以至少部分降低后代发展超重、肥胖、过量脂肪积聚和/或相关代谢紊乱的风险。这样的量被定义为“预防有效剂量”。因此,维生素B12可以预防有效剂量施用。
例如,可将维生素B12以对应于0.26至26μg维生素B12/天的量(例如,以对应于1至14μg维生素B12/天的量)来施用。
针对本发明的目的,优选的是定期施用维生素B12,例如一天两次、一天一次、两天一次或每周一次。
可将维生素B12作为持续释放制剂来提供。如果是这样,使用维生素B12的频率可降低,同时身体仍能持续获得足够的维生素B12供应。
例如,可将维生素B12在孕前、部分或整个孕期和/或母乳喂养期间(哺乳期)来施用。在一个实施方案中,可将维生素B12在孕期和/或哺乳期来施用。
在一个实施方案中,将本发明的组合物在孕前施用,例如在孕前或准备怀孕前1、2或4个月施用。
随着怀孕中三个月(尤其是怀孕末三个月)的营养需求不断增加,可能优选的是在怀孕末三个月或在怀孕中三个月和末三个月定期施用维生素B12。
例如,可每天施用维生素B12。孕期和/或哺乳期定期施用维生素B12可持续至少4、至少8、至少12、至少16、至少20、至少24、至少28、至少32或至少36个连续周。
维生素B12可以纯净物形式来使用,也可作为天然维生素B12源或其提取物来使用。
可使用高度纯化或合成的维生素B12。优选的是维生素B12由天然源提供,或维生素B12作为天然源被提供。
例如,维生素B12可由天然源提供,所述天然源为例如有壳的水生生物、鱼类、器官肉(如肝脏)、肉类、家禽、蛋类、奶、酸奶、奶酪、奶制品;或它们的提取物和/或组合物。
维生素B12可用作单一活性成分。
维生素B12还可与一种或多种其他化合物来共同施用,如果将这些化合物施用于孕前、孕期和/或哺乳期的母亲,这些化合物将具有降低后代发展超重、肥胖、过量脂肪积聚和/或相关代谢紊乱的风险的活性。
根据本发明,维生素B12可用于预防后代(尤其是超重、肥胖妇女和/或患有代谢综合征的妇女的后代)在以后的生活中发生超重、肥胖、过量脂肪积聚和/或相关代谢紊乱。
“在以后的生活中”包括儿童期和成人期。例如,“在以后的生活中”可指儿童期,例如至少3岁,例如至少4岁或至少6岁。
本发明人发现,本发明的主题尤其允许通过降低和/或避免后代脂肪量(例如腹部和/或内脏的脂肪量)过量堆积来预防超重和/或肥胖。
这是非常有利的,因为腹部脂肪尤其与心血管疾病和其他代谢疾病和血管疾病(例如,2型糖尿病)紧密相关。内脏脂肪(又称腹内脂肪)位于腹腔内、内部器官和躯干之间,而且与2型糖尿病紧密相关。
可能优选的是,根据本发明将维生素B12施用于其孩子尤其存在发展超重、肥胖、过量脂肪积聚和/或相关代谢紊乱的风险的母亲和/或孕妇。
形成本发明的研究表明,这些母亲和/或孕妇可能是(例如)超重和/或肥胖的母亲,以及/或者多次生育的母亲。
“生育次数”是指女性生育小孩的次数的术语。妇女已生育两次或更多次即为多次生育。
本发明还涉及可用于本发明目的的孕产妇食物组合物。
因此,本发明涉及一种孕产妇食物组合物,其中所述孕产妇食物组合物是粉状营养配方食品,其包含:蛋白质源、碳水化合物源、脂质源、卵磷脂(优选大豆卵磷脂)、增量剂和0.37至18.2μg维生素B12/100g干重。
蛋白质源可以是奶粉或脱脂奶粉。蔗糖和/或麦芽糖糊精可用作碳水化合物源。脂质源可以是植物油。还可添加维生素和矿物质。例如,可根据政府机构(如USRDA)的建议添加维生素和矿物质。例如,日剂量单位的组合物可包含以下给定范围内的微量营养素中的一种或多种:100至2500mg钙、35至350mg镁、70至3500mg磷、2.7至45mg铁、1.1至40mg锌、0.1至10mg铜、22至1,100μg碘、6至400μg硒、77至3000μg维生素A或视黄醇活性当量(RAE)、8.5至850mg维生素C、0.14至14mg维生素B1、0.14至14mg维生素B2、1.8至35mg烟酸、0.19至19μg维生素B6、60至1000μg叶酸、3至300μg生物素、1.5至100μg维生素D、1.9至109μg维生素E。
作为另一种选择或除此之外,制剂还可包含葡萄糖浆、乳脂、鱼油、柠檬酸镁、胆碱盐和胆碱酯、益生菌培养物、益生元纤维和/或抗坏血酸棕榈酸酯。
例如,可添加风味物化合物(例如,可可粉或蜂蜜)来提供不同口味。
组合物还可包含益生菌、叶酸、钙、铁、ARA、EPA和/或DHA。
本领域的技术人员将理解,在不脱离所公开的本发明范围的前提下,他们可以自由地组合本文所述的本发明的所有特征。具体地讲,针对本发明的用途而描述的特征可适用于本发明的孕产妇食物组合物,反之亦然。
尽管以举例的方式对本发明进行了描述,但应当理解,在不脱离权利要求书中所限定的本发明范围的前提下,可作出变型和修改。此外,对于具体的特征如果存在已知的等同物,则应这些等同物引入本说明书中,如同在本说明书中明确提到这些等同物。参见附图和非限制性实例后,本发明的更多优点和特征将变得显而易见。
附图说明:
图1示出了怀孕后期缺乏维生素B12(血清水平<200ng/L)的妇女生育的后代在4岁和6岁时具有更严重的儿童肥胖,其中肥胖利用双能X射线吸收测量法(DXA)测定。在小图a)中,孕产妇维生素B12缺乏与后代4岁时的脂肪量百分比显著相关,在图b)中观察到后代6岁时的脂肪量百分比趋势。
实施例:
实验和临床研究表明,孕期的孕产妇营养状态对后代在以后的生活中的结果具有终身影响。在我们的研究中,我们试图鉴定出临床学和营养学所定义的组,这些组的后代在以后的生活中出现未达标身体组成的风险增加。
研究设计:
分析中包括的母婴群体:
选择了英国南安普敦妇女调查(Southampton Women’s Survey,SWS)中的501对母婴,采集怀孕后期孕产妇血清试样,并利用DXA测定其后代在4岁和6岁时的身体组成。所分析的SWS受试对象的特征概要如下:
1)测量孕产妇血清样品中的维生素B12
利用自动免疫分析法分析维生素B12,具体是利用贝克曼库尔特公司(Beckman Coulter)的DXi 800(一种连续随机存取分析仪)的“Access免疫分析系统”进行分析。(Badiou S,Bariolet S,Laurens C,Aillaud N,BargnouxAS,Mariano-Goulart D,Dupuy AM,Cristol JP.Comparison of isotopic andimmunoenzymatic methods for folate and vitamin B12 determination.Clin Lab.2010;56:547-52(Badiou S,Bariolet S,Laurens C,Aillaud N,Bargnoux AS、Mariano-Goulart D,Dupuy AM,Cristol JP,“利用同位素法和免疫酶标法测定叶酸和维生素B12的比较”,《临床检验》,2010年,第56卷,第547-552页))。维生素B12的Access分析是一种顺磁粒子化学发光免疫分析法,该方法利用Access免疫分析系统(贝克曼公司的DxI 800(Beckman DxI 800))来定量测定人血清和血浆(肝素)中的维生素B12。维生素B12的Access分析是一种竞争结合免疫酶标分析,其总不精确度小于整个分析范围的12%。区别于零且置信度为95%的维生素B12最低可检测水平为50pg/mL(37pmol/L)。
质量控制数据(两台机器)如下表所示:
水平1水平2水平3 | |
平均值 | 107.5/98.7555.1/527.81093.4/1080.0 |
标准偏差 | 9.65/12.242.4/34.9107.1/126.4 |
变异系数百分比 | 9.65/12.356.29/8.049.79/11.70 |
判定血浆或血清中维生素B12缺乏和维生素B12耗尽的建议截止值分别为<148pmol/L(<200pg/mL)和<221pmol/L(<300pg/mL)(Simpson JL,Bailey LB,Pietrzik K,Shane B,Holzgreve W.Micronutrients and women ofreproductive potential:required dietary intake and consequences of dietarydeficiency or excess.Part I--Folate,Vitamin B12,Vitamin B6.J Matern FetalNeonatal Med.2010Dec;23(12):1323-43(Simpson JL,Bailey LB,Pietrzik K,Shane B,Holzgreve W,“微量营养素与有生育潜能的妇女:必需饮食摄入以及饮食缺乏或饮食过量的后果,第I部分—叶酸、维生素B12、维生素B6”,《孕产妇、胎儿与新生儿医学杂志》,2010年12月,第23卷(第12期),第1323-1343页);Institute of Medicine and Committee(IOM).Dietary reference intake:folate,other B vitamins and choline.Washington,DC:National Academy Press;199.8(医学研究所和委员会(IOM),《饮食参考摄入量:叶酸、其他B族维生素和胆碱》,华盛顿特区美国科学院出版社,1998年))。
对于上述分析,使用200pg/mL(或200ng/L)以下的血清B12水平来指示缺乏B12的状态。
2)进行统计分析,以揭示SWS中缺乏维生素B12与儿童期肥胖的相 关性。
所有SWS儿童的脂肪量变量均呈正偏斜,利用Fisher-Yates正态分数将其转换为平均值为0、标准偏差为1的正态分布变量(Armitage P,BerryG.Statistical methods in medical research.Oxford,United Kingdom:BlackwellScience Ltd,2002(Armitage P和Berry G,《医学研究的统计方法》,英国牛津Blackwell Science公司,2002年))。以身体组成变量为结果变量,孕产妇微量营养素状态为预测变量,同时考虑可能的影响因素,利用线性回归模型进行拟合。由于儿童身体组成存在性别差异,因此所有的分析均针对儿童性别和儿童年龄进行了调整。利用Stata 11.1(StataCorp.Stata版本11统计软件,德克萨斯州大学城(College Station,TX):StataCorp LP,2009年)执行统计分析。上文描述了用于微量营养素缺乏/不足的统计分析的阈值。
结果:
血清样品中的维生素B12测定结果表明,维生素B12缺乏在南安普敦的妊娠后期孕妇中极为普遍,501个受试对象中就有64.5%的血清维生素B12水平低于200ng/L。
怀孕后期缺乏维生素B12与后代4岁时的较高脂肪量(利用DXA测量)相关,在后代6岁时显示出趋势。
表1.孕产妇维生素B12状态所致的儿童肥胖。
表1所示的结果对应于用于对图1中所绘测量结果进行统计分析的对数变换值。4岁时的脂肪含量百分比分布没有倾斜,因此未进行对数变换。
平均血清维生素B12水平根据孕前BMI具有显著差异(表2),肥胖母亲被鉴定为存在更高的缺乏孕产妇维生素B12的风险(表3)。
表2.根据孕前BMI的维生素B12状态。
孕前BMI | 平均血清维生素B12水平(ng/L) |
<18.5 | 197.3 |
18.5-25 | 170.2 |
25-30 | 164.3 |
>30 | 143.7 |
P值(得自ANOVA) | 0.009** |
表3.根据孕前BMI,维生素B12缺乏风险增加。
这些结果为维生素B12缺乏对后代肥胖风险具有持久影响以及肥胖母亲存在更高风险这些观点提供了支持,并且为在孕前、孕期和哺乳期对肥胖母亲进行干预以改善孕产妇维生素B12状态提供了强有力的支持。
Claims (14)
1.用于预防超重和/或肥胖母亲的后代发生肥胖和/或与肥胖相关的代谢紊乱的维生素B12的用途,其中将所述维生素B12在孕前、孕期和/或哺乳期施用于所述母亲。
2.根据权利要求1所述的维生素B12的用途,其中所述维生素B12以孕产妇食物组合物的形式来施用。
3.根据权利要求2所述的维生素B12的用途,其中所述孕产妇食物组合物选自粉状营养组合物、营养配方食品、基于谷类的产品、饮料、食品棒、营养补充剂、营养品、酸奶、乳制品、食物喷洒物、丸剂或片剂,所述粉状营养组合物要在奶或水中重构。
4.根据前述权利要求中任一项所述的维生素B12的用途,其中所述维生素B12以对应于0.26至26μg维生素B12/天、例如1至14μg维生素B12/天的量来施用。
5.根据前述权利要求中任一项所述的维生素B12的用途,其中将所述维生素B12在孕前、孕期和/或哺乳期施用至少4个连续周。
6.根据前述权利要求中任一项所述的维生素B12的用途,其中所述维生素B12以至少每天一次的频率来施用。
7.根据前述权利要求中任一项所述的维生素B12的用途,其中所述维生素B12由天然源提供,所述天然源为例如有壳的水生生物、鱼类、器官肉如肝脏、肉类、家禽、蛋类、奶、酸奶、奶酪、奶制品;或它们的提取物和/或组合物。
8.根据前述权利要求中任一项所述的维生素B12的用途,其中所述后代在以后的生活中的肥胖和/或相关代谢紊乱得以预防。
9.根据权利要求8所述的维生素B12的用途,其中肥胖在至少3岁、例如至少4岁或至少6岁的后代中得以预防。
10.根据前述权利要求中任一项所述的维生素B12的用途,其中通过降低脂肪量尤其是腹部和/或内脏的脂肪量来预防肥胖。
11.孕产妇食物组合物,其中所述孕产妇食物组合物是粉状营养配方食品,所述粉状营养配方食品包含蛋白质源、碳水化合物源、脂质源、卵磷脂、增量剂和0.18-18.2μg维生素B12/100g干重。
12.根据权利要求11所述的孕产妇食物组合物,还包含益生菌、叶酸、钙、铁、ARA、EPA和/或DHA。
13.用于预防超重和/或肥胖母亲的后代具有过量脂肪积聚或发生超重的维生素B12的用途,其中将所述B12在孕前、孕期和/或哺乳期施用于所述母亲。
14.根据权利要求13所述的维生素B12的用途,其中所述后代在以后的生活中的过量脂肪积聚或超重得以预防。
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US8603555B2 (en) | 2010-04-13 | 2013-12-10 | Mark A. Innocenzi | Methods for quantifying the complete nutritional value of a standard equivalent unit of the nutritional value of one serving of fruits and vegetables (SFV)and for fortifying a base food to contain same for human consumption |
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2015
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Non-Patent Citations (2)
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KRISHNAVENI等: "Low plasma vitamin B12 in pregnancy is associated with gestational ‘diabesity’ and later diabetes", 《DIABETOLOGIA》 * |
KUMAR等: "Maternal dietary folate and/or vitamin B12 restrictions alter body composition (adiposity) and lipid metabolism in Wistar rat offspring", 《JOURNAL OF NUTRITIONAL BIOCHEMISTRY》 * |
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RU2016132886A3 (zh) | 2018-09-06 |
RU2016132886A (ru) | 2018-02-14 |
US11065271B2 (en) | 2021-07-20 |
EP3091988B1 (en) | 2020-09-02 |
EP3091988A1 (en) | 2016-11-16 |
US10517891B2 (en) | 2019-12-31 |
MX2016009038A (es) | 2017-02-08 |
PH12016500915A1 (en) | 2016-06-20 |
ZA201605485B (en) | 2018-05-30 |
US20200188421A1 (en) | 2020-06-18 |
AU2015205515A1 (en) | 2016-06-02 |
CL2016001751A1 (es) | 2017-02-17 |
ES2832552T3 (es) | 2021-06-10 |
WO2015104391A1 (en) | 2015-07-16 |
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