CN101193560A - 海豹油和冷榨初榨橄榄油的组合 - Google Patents
海豹油和冷榨初榨橄榄油的组合 Download PDFInfo
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Abstract
一种作为常规饮食的补充，或其组分的油类组合，其中它包含海产油类，优选海豹油，和冷榨初榨橄榄油。
Description
本发明涉及油类的组合，其作为常规饮食的补充剂或组分，能抵抗冠心病(CHD)、血栓生成和其他炎性疾病例如牛皮癣和风湿病。本发明的组合包括海豹油和初榨橄榄油。
动脉粥样硬化性损伤形成于当循环系统的三种细胞成分，即单核细胞、血小板和T-淋巴细胞，与LDL-胆固醇和动脉壁中的两种细胞类型，即内皮细胞(EC)和平滑肌细胞(SMC)发生反应时。
动脉粥样硬化的预兆是外周血中的单核细胞和淋巴细胞向血管壁内膜中的募集，该事件看来取决于大量LDL的局部存在。随着LDL的积累，结合的脂质和蛋白质被氧化和糖基化。血管壁细胞似乎将这种变化看作危险信号并需要身体的防御系统的增援。这些过程看来可促进内皮细胞上的粘着分子，尤其是血管细胞粘着分子-1(VCAM-1)和细胞内粘着分子-1(ICAM-1)的正调节。因此，引发单核细胞和淋巴细胞募集。这导致单核细胞的变移增加，内皮上的粘着分子的正调节暴露，和化学引诱物的产生和释放。这些是单核细胞向内膜转移，以及同时发生的单核细胞分化成巨噬细胞的必需事件。有效修饰LDL也是巨噬细胞进一步发展为泡沫细胞(脂肪巨噬细胞)的必要条件，这是在血管壁的内皮下形成脂纹的主要原因。LDL的修饰形式(氧化的，糖基化的等等)值得特别的注意，因为LDL的修饰与通过由于单核细胞和淋巴细胞的粘着和向内膜变移而启动的过程触发的炎症反应相关。
如上所述，众所周知单核细胞在动脉粥样硬化的早期起重要的作用。在动脉粥样硬化过程中最初发生的事件之一就是单核细胞向内膜的转移。由于单核细胞的募集和其穿过内皮与激活产物，例如细胞因子和生长因子的分泌相关，可以设想循环单核细胞的功能反应性是非常重要的。有人提出慢性传染病可能通过激活单核细胞并使它们对应激作出反应更易于产生且释放有害产物例如细胞因子和趋化因子而影响功能反应性。
至今，人们对于循环单核细胞的功能性质究竟与动脉粥样硬化如何有关知之甚少。然而，大家公认的是高活性的单核细胞在风湿病，牛皮癣和其他炎性疾病的病理生理学中起决定性作用。我们还知道动脉粥样硬化是一种促炎疾病。因此可假设循环单核细胞的促炎功能可伴随冠心病(CHD)的风险增加，并且高胆固醇水平可能增加促炎产物，例如氧自由基、细胞因子等的生成。
多年来，发明人通过监测脂多糖(LPS)刺激的血液中促凝血酶原激酶(组织因子＝TF)以及细胞因子例如TNFa和IL-6的产生已经观察到单核细胞的反应性在低活性的个体至非常高活性的个体(高反应者)之间变化。单核细胞的这种性质似乎是遗传的(φsterud等人，″Biood Coagulation and Fibrinolysis″2002；13：399-405)。发明人特别在体外研究了其近亲家族中有心肌梗塞(MI)或癌症病史的健康个体的全血中单核细胞由LPS诱导的活性与血清中脂质分布型之间有怎样的联系。在一共54名心肌梗塞(MI)家族的个体中，20名具有中等高胆固醇(7.1-10.2mmol/l)，而34名具有正常胆固醇。在具有正常胆固醇的个体中，19名具有高活性的单核细胞(高反应者)，而15名具有正常反应性单核细胞。正常胆固醇水平组的LPS诱导的促凝血酶原激酶(TF)、TNFa和IL-6比中等高胆固醇组平均高3-4倍。因此，没有发现高活性的单核细胞和胆固醇水平之间正向相关。在具有癌症病史的家族中一共42名个体的胆固醇水平正常，并且LPS诱导的促凝血酶原激酶(TF)、TNFa和IL-6与在心肌梗塞(MI)家族中具有中等高胆固醇水平组的值相比没有显著性差异。这支持一个结论，即中等高胆固醇与全血中单核细胞活化的增加不相关，而高活性的外周血单核细胞是冠心病发展的一个显著危险因子。
降低单核细胞的反应性，并因此减少促炎产物例如细胞因子，氧化代谢物和生长因子的产生与降低胆固醇水平相比至少是同样重要的。新近的研究也表明他汀类药物的抗炎作用可能比其降低胆固醇的作用更为重要(Balk等人″Effects of statins on nonlipid serum markers associated withcardiovascular disease：a systematic review″Ann Intern Med.2003；139：670-82.Review)。
本发明的食用油包含ω-3脂肪酸。已知其可降低能导致猝死的心律不齐的风险。也已知ω-3脂肪酸可降低能导致心脏病发作和中风的血栓形成的风险。它们可降低动脉粥样硬化斑的生长速度，因此其具有抗炎性质，因为粥样化过程中损伤形成是通过促炎反应介导的。此外，ω-3脂肪酸可改善内皮功能，降低血液中甘油三酯的水平并轻微降低血压(简略的概述，参考PMKris-Etherton，WS Harris，LJ Appell″Arterioscler Thromb Vasc Biol.″2003；23：151-2)。
考虑到ω-3脂肪酸的性质，预期ω-3脂肪酸补充剂应当足以预防心血管疾病。然而，在挪威进行的临床研究已经表明ω-3脂肪酸的副作用(I Seljefot，O Johansen，H Arnesen，JB Eggesbo，AB Westvil，P Kierulf，″ThrombHaemos t.″1999；81：566-70；O Johansen，I Seljefot，AT Hostmark，H Arnesen″Arterioscler Thromb Vasc Biol.″1999；19；1681-6)。给患有心血管疾病的患者补充ω-3脂肪酸6个月后，其经受的心绞痛和阻塞均为对照组的两倍。还观察到细胞因子生成的增加，它表示体内多不饱和脂肪酸的促炎过氧化作用的增加(简略的概述，参考H.Arnesen，″Lipids″2001；36 Suppl：S103-6)。
上述发现与发明人自己的对于包含ω-3脂肪酸补充剂的饮食的研究结果相一致。因此，健康个体的含有ω-3脂肪酸浓缩剂的补充性饮食与以鳕鱼肝油(cod-liver oil)(CLO)形式的相应量的ω-3脂肪酸相比抗炎作用并不显著。另一方面，本发明的油类的组合每天摄入15ml食用10周后显著降低了LPS诱导的细胞因子和类花生酸的产生。
利用现代精炼工艺从鱼类和海洋哺乳动物中生产油类的目的是使油类更健康、更安全、更美味和更稳定利于储存。然而，为了增强感官性质而除去产生不良味道或气味的分子可能破坏有效力的抗氧化剂。生物学活性分子的定量含量也景响营养品质。这些营养素受几种因素影响，例如环境、利用率、化学稳定性、加工的成度和递送营养物的形式。鱼油从全鱼，鱼肝(主要是鳕鱼肝)或副产物(主要是鲑鱼)中提取。来自海洋哺乳动物的油类由鲸脂和外部脂肪组织生产。
将海产油类加工使它们适于人类食用可能是有困难的。传统提取技术包括加热或蒸汽提取原料以释放出脂质。海产油类含有大量不饱和脂肪酸。提取过程中采用高温将导致一些不良改果例如开始氧化反应，破坏抗氧化剂和形成使油产生臭味和气味的分子。在加热提取过程中当温度高于40℃时，在脂质组分中与其在细胞中的“初榨”状态相比，发生可检测到的变化。为得到稳定、感官上可接受的和安全的产品，除去很多成分(蛋白质、肽、氨基酸、游离脂肪酸、磷脂、色素、固醇、转化产物、金属和可能的毒性物质)通常是必不可少的。常规的精炼方法由四个主要步骤：磨光、酸洗、漂白和除臭组成。此外，还使用例如澄清(过滤，沉降)、不同批次的混合、冬化和磨光过滤等步骤。在精炼步骤中，许多化学反应(水解、自动氧化、异构化、结合、聚合、热解和脱水)将不依赖该工艺条件而发生。精炼过程必须考虑到除去任何可能形成的不良的副产物。处理步骤的个数也受到粗制油的品质的影响，包括伴随的物质、杂质的量和类型、已形成物质的氧化和水解损害。在选择精炼方法时，食用油的品质标准、环境条件、资金和原料损失的减少都是至关重要的标准。
为改善海产油类的感官性质和稳定性而进行精炼时，还可能破坏有效力的抗氧化剂和具有潜在的有益功能特性的组分。多不饱和脂肪酸，包括ω-3脂肪酸可以被掺入至LDL颗粒中并使它们更易于氧化。由于LDL颗粒的氧化作用是动脉粥样硬化早期的主要反应之一，预防氧化将防止泡沫细胞在内膜中的生成(概述，参考Bφsterud，E Bjφrklid，″Physiological Reviews″，2003，83：1069-112.Review)。因此，抗氧化剂已显示出在动物模型中可减少损伤形成(M.Aviram，B.Fuhrman″Ann N Y Acad ScL″2002；957：146-61.Review)。此外，抗氧化剂在类花生酸代谢的负调节中也很重要。抗氧化剂可抑制导致生成白细胞三烯B4和其他物质的脂肪氧合酶途径，并随后减少LTB4的生成。最近，特别证明了在易患有动脉粥样硬化的转基因小鼠中抑制LTB4受体使损伤生成减少了约70％(RJ Aiello，PA Bourassa，S Lindsey，W Weng，A.Freeman，HJShowell，″Aterioscler Thromb Vasc Biol.″2002；22：443-9)。
食用本发明的食用油长达10年的受试者(发明人)在LPS诱导的全血中具有非常低的LTB4生成。向受试者的血液中加入市售的LTB4导致LPS诱导的TF(组织因子)升高超过70％，并且血液对LPS的反应再次达到最高(φsterud，未公开数据)。
本发明的油类的组合结合了ω-3脂肪酸的作用和在体外和体内都产生抗氧化作用的协同组分。根据本发明，假如该组合具有出人意料的有利性质，则这种形式具有非常好的临床效果，更好的功能特性和更长的保存期。发明人已经证明了使用包含来自海洋哺乳动物，优选海豹的油和冷榨初榨橄榄油的产品可获得特别有益的效果，上述这些组分可由已知方法生产。如果各个组分单独使用，所获得的效果看来可能比预期的效果更显著。
因此，本发明涉及油类的组合，其作为常规饮食的补充剂，特征在于它包含海豹油和冷榨初榨橄榄油的组合。
本发明还涉及本发明的组合作为食物中水包油或油包水乳剂的组分的用途。
此外，本发明还涉及本发明的组合，任选地与辅料一起，例如用于制备抵抗冠心病和血栓形成的发展和用于抑制牛皮癣、风湿病和其他促炎疾病的用途。
对于使用本发明的食用油作为健康个体的日常补充剂的效果已经进行了两项临床研究。在第一项研究中，在对照组和接受本发明的食用油的组中分别有28名参与者，同时在鳕鱼肝油(CLO)组中有37名参与者。12周内每人每天食用15ml油或不食用油(对照组)。尽管CLO组与食用本发明的油的组合的组相比，个体的血清中ω-3脂肪酸具有较高的上升，但是全血中LPS诱导的TNF在接受本发明的油类组合的组中减少了24.0％，与之相比，在CLO组中减少了5.0％。如同之前所提到的研究一样，此项研究表明在受激血细胞中炎性产物量的减少并不与ω-3脂肪酸的含量直接相关(φsterud等，1995)。
另一项研究的结果见表1：
表1.CLO或本发明的油类的组合作为饮食补充剂与对照相比的效果(与摄入饮食之前获得的数值相比的％变化)
| 组 | HDL-chol | HsCRP | MCP-1 | TxB2 | LTB4 |
| 对照 | 0 | +5.1 | +8.5 | 0 | +36.6 |
| CLO | +1.4(i.s.) | +12.5(n.s.) | -5.2(0.005) | -14.3(0.05) | +8.6(0.001) |
| 本发明的油 | +8.3(0.05) | -24.0(0.001) | -14.3(0.05) | -17.6(0.05) | +8.8(0.001) |
表1显示与冠心病(CHD)相关的最重要的一些参数的变化。HDL-chol是有益的胆固醇并且其任何阳性变化都是有益的。超敏感性C-反应蛋白(hs-CRP)反映了身体内的慢性炎症反应。已经证实，0-5mmol/l的增加的值是冠心病的良好的危险指示，且尤其当与hs-CRP相关的HDL胆固醇占总胆固醇的比例增加时(Rifai N，Ridker PM″Inflammatory markers and coronary heart disease″Curr Opin Lipidol.2002；13：383-9.Review)。单核细胞趋化蛋白-1(MCP-1)是非常重要的化学引诱蛋白，其在动脉粥样硬化的发展中起主要作用，因为其在促炎物质产生的部位调动它们。因此，任何降低MCP-1的饮食补充剂可能都是非常有益的。LTB4和TxB2(TxA2的稳定产物)是源自花生四烯酸的代谢的促炎产物。
分别对对照组、CLO和接受本发明的食用油的组中的23、18和19名健康者进行了上述研究。在研究开始前以及在12周连续补充性食用15g油(或不食用＝对照组)后立即从08.00至10.00之间禁食的志愿者中取样。在血清样品中测定之前和之后的脂肪酸组成。
上述研究的结论是本发明的油类的组合具有增加有益的HDL胆固醇、显著降低冠心病的重要标记和危险因素(hs-CRP)并且与CLO相比进一步更有效地降低MCP-1的潜力。此外，减少促炎产物TxA2和LTB4的有益作用处于与CLO相同的水平。总体来说，本发明的食用油作为饮食补充剂与CLO相比具有显著更强的抗炎效果，并且优于橄榄油，其在几项ω-3脂肪酸和鱼油的研究中也被单独用作对照。本发明的可食用油的效果很可能通过来自海产油的ω-3脂肪酸和存在于初榨橄榄油中的强抗氧化性的协同组合而产生。
Claims (5)
1.一种作为常规饮食的补充，或其组分的油类的组合，其特征为包含海豹油，和冷榨初榨橄榄油。
2.如权利要求1所述的组合，特征为该组合的形式为混合物。
3.如权利要求1所述的组合，特征为海豹油和初榨橄榄油的比例为1∶9至9∶1，优选2∶8至8∶2，更优选3∶7至7∶3，更优选4∶6至6∶4，且最优选1∶1。
4.权利要求1所述的组合作为可食用油或作为水包油或油包水乳剂的组分在食品中的用途。
5.权利要求1所述的组合，任选地与辅料一起，用于制备抵抗冠心病和血栓形成的发展和用于抑制牛皮癣、风湿病和其他促炎疾病的组合物的用途。
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