TW201032734A - Nutritional composition for infants - Google Patents
Nutritional composition for infants Download PDFInfo
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- TW201032734A TW201032734A TW098146464A TW98146464A TW201032734A TW 201032734 A TW201032734 A TW 201032734A TW 098146464 A TW098146464 A TW 098146464A TW 98146464 A TW98146464 A TW 98146464A TW 201032734 A TW201032734 A TW 201032734A
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- nutritional composition
- acid
- content
- obesity
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Description
201032734 六、發明說明: 【發明所屬之技術領域】 本發明係關於一種營養組合物,更具體言之係關於一種 嬰兒用之營養組合物’其有助於降低日後罹患肥胖症之風 險。 【先前技術】 向所有嬰兒推薦母乳。然而在一些情況下,由於若干醫 ❹學原因,母乳餵養係不充足或不成功或不聽勸告或母親根 本未選擇母乳餵養或未選擇母乳餵養之時間超過數週。針 對該等情況’已研發嬰兒配方。 在美國及全球範圍内,成年人、兒童及青少年中肥胖症 及超重的普遍性已於過去30年内快速增長且仍在不斷上 升。目岫,兒里期超重及肥胖在全球範圍内影響18〇〇萬名 5歲以下兒童。近30%美國兒童及青少年及1〇至3〇%之歐洲 兒童超重或肥胖。 # 曰益認爲出生頭6個月係人類脂肪質量發展之最重要產 後期之’因此係日後漸進形成過度肥胖之關鍵時期。此 外,人類流行病學數據及動物研究證實,於出生時或嬰兒 期間所增加的體重與曰後罹患諸如代謝综合症、2型糖尿 病及心血管問題之疾病的風險相關。 版他⑽等人研究母親膳食中亞油酸(LA)對α•亞麻酸 (ALA)之比率對其喷乳幼畜期間之血清瘦素漢度之影響, 並發現與彼等其母親食用同時含LA及ALA(LA/ALA比為 9.0)之腾食的幼畜相比,對母㈣以富含ala(la/ala比 145394.doc 201032734 為0.42)之膳食時,接受哺乳之幼畜之企清瘦素濃度較低。 母親食用富含LA(LA/ALA比為216)之膳食的第三組幼畜之 平均血清痩素濃度係介於其他兩組濃度之間,但彼此無明 顯差異。因先前大量研究已顯示,在圍產期之循環瘦素濃 度對正常發育及健康具重要作用·,所以作者選擇研究幼畜 的血清痩素濃度。基於該等發現,繼而預測母親膳食中 LA與ALA間的平衡而非LA或ALA本身之量對脂肪組織生 長具重要作用(Korotkova,等人,「Leptin levels in rat offspring are modified by the ratio of linoleic to a-linolenic acid in the maternal diet」,Journal of Lipid Research, 43 卷,2002, 1743-1749頁)。 於W02008/054192中,主張嬰兒的總脂肪組織質量並非 確定日後患病風險的良好預測值,反而應注意嬰兒早期所 累積的内臟脂肪質量。已證明内臟脂肪細胞量主要係於嬰 兒期内確定,且W02008/054192之發明者確信,在此期間 控制内臟脂肪生成為有用之作法。W02008/054192中所建 議的方案係降低餵養嬰兒之LA量,以使LA/ALA比介於2 與6之間,同時保證LA量低於總脂肪酸之14_5重量%。 然而,由於LA及ALA均係必需脂肪酸,亦即無法由人體 合成之脂肪酸,因此就人類嬰兒的營養方面,此方法可能 受到實際應用之限制。 因此,顯然需要一種旨在兒童期減少脂肪質量累積,進 而降低日後罹患肥胖症之風險及罹患與該肥胖症相關的疾 病之風險的替代營養方法。 145394.doc 201032734 【發明内容】 本發明者已出人意料地發現,於嬰兒期餵食相對富含α_ 亞麻酸之組合物會減少日後總脂肪質量的累積。 因此,本發明提供一種營養組合物,其包含一種蛋白質 源、種月曰質源及一種碳水化合物源,其中以佔總脂肪酸 含量之百分比表示,該脂質源分別包含至少丨6重量%亞油 酸及至少2重量% α·亞麻酸,且其含量使亞油酸:α_亞麻 ❹ 酸之比例介於1至10之間。 本發明亦提供一種以亞油酸及α-亞麻酸於製造一種用於 投與初生6個月内的嬰兒的營養組合物,以降低日後發展 成肥胖症風險上之用途,其中該組合物以佔該組合物中總 脂肪酸含量之百分比表示,分別包含至少16重量%亞油酸 及至少2重量% α_亞麻酸,且其含量使亞油酸:α_亞麻酸 之比介於1至10之間。 本發明進一步提供一種降低嬰兒日後罹患肥胖症之風險 粵之方法,其包括對出生6個月内的嬰兒飯養-種營養組合 物,*亥營養組合物包含一種蛋白質源、一種脂質源及一種 碳水化合物源,其中以佔總脂肪酸含量之百分比表示該 月曰質源分別包含至少丨6重量%亞油酸及至少2重量% α_亞麻 酸且其含量以使亞油酸:α-亞麻酸之比例介於1至1〇之 間。 在不欲受理論之侷限下,依據其實驗觀察,本發明者確 仏’嬰兒期健養富含〜亞麻酸之膳食可依某種方式減少脂 W生成且減少脂肪細胞之尺寸增大中任一項或兩項,且此 145394.doc 201032734 等效益可持續至日後,進而降低日後罹患肥胖症之風險。 此外,已知肥胖症與增加諸如可能發展為2型糖尿病之胰 島素抵抗及葡萄糖失耐的病況之風險相關。 【實施方式】 於本說明書中,以下表述具有如下定義: 「ALA」意指α-亞麻酸(ci8:3n-3); 「嬰兒」意指未滿12個月之兒童,且「嬰兒期」應相應 地理解;就本發明之目的而言,術語「嬰兒」包含幼嬰動 物,如幼寵物、幼犬、幼馬或幼貓。 「LA」意指亞油酸(ci8:2n-6); 就嬰兒而言’「日後」意指嬰兒期之後生命中的任何時 間點。此時間點之一實例可為脂肪細胞反彈時之年齡,其 一般於人類嬰兒的5至6歲期間發生。 除非另外說明外,否則所有百分比及比例皆為重量比。 根據本發明之營養組合物包含至少16重量%LA及至少2 重量% ALA。LA含量較佳介於總脂肪酸之18至3〇%之間, 更佳係介於18至25%之間。ALA含量較佳係介於總脂肪酸 之2至12%之間,更佳係介於6至11%之間。la:ala比例較 佳係介於2至6之間。 本發明之營養組合物較佳具有小於i 85 g/1〇〇 “a丨之蛋 白質含量。只要滿足對於必需胺基酸含量之最低需求且確 保令人滿意的生長,則認爲蛋白質源之具體組成對本發明 並不重要。因此,可使用基於諸如乳清、酪蛋白及其混合 物的牛奶蛋白質之蛋白質源’以及基於大豆的蛋白質源。 145394.doc 201032734 然而,以乳清與酷·蛋白蛋白質之混合物為較佳。路蛋白: 乳清比可介於70:30至30:70之間,但較佳係30:70。 蛋白質源中之蛋白質可係完整或經部分水解,或可使用 完整蛋白質與水解蛋白質之混合物。若需滿足對必需胺基 酸含量之最低需求,則該蛋白質源可另補充游離胺基酸。 此等需求已於例如EC Directive 2006/141/EC中公佈。 如上所述,較佳蛋白質源係酪蛋白與乳清蛋白之混合 φ 物。該乳清蛋白可係乳清蛋白分離物、酸乳清、甜乳清或 其中已移除酪蛋白-糖巨肽之甜乳清(經改質的甜乳清)。然 而,乳清蛋白較佳係經改質的甜乳清。甜乳清係製作乾酪 之易得的副產品且常用於製造基於牛奶的營養組合物。然 而,甜乳清包含一種稱為酪蛋白-糖巨肽(CGMP)之組份, 該組分不幸地富含蘇胺酸且缺乏色胺酸。自甜乳清中去除 CGMP得到一種蘇胺酸含量更接近人乳之蛋白質。EP 880902中闡述一種自甜乳清中去除CGMP之製程。 ❹ 若經改質的甜乳清在70%乳清與30%酪蛋白混合物中作 為乳清蛋白質時,則該蛋白質源可補充之游離組胺酸量為 總蛋白質含量的0.1至0.3%。 本發明之營養組合物含有碳水化合物源。該碳水化合物 源較佳係乳糖,但亦可添加諸如蔗糖、麥芽糊精、及澱粉 的其他碳水化合物。該營養組合物中碳水化合物含量較佳 係介於9與14g/100kcal之間。 本發明之營養組合物含有脂質源。除LA及ALA外,該脂 質源可包括適用於餵養嬰兒之營養組合物之任何脂質或脂 145394.doc 201032734 肪。較佳脂肪源包括椰子油、低芥酸菜籽油(菜軒、、由 (canola oil))、大豆卵磷脂、棕櫚油精、及葵花油。脂質原 亦可包括少量預形成的長鏈多不飽和脂肪酸花生四稀酸 (C20:4n-6)及二十二碳六稀酸(C22:6n-3)。魚油係適宜的_ 十二碳六烯酸源’或單細胞微生物油係適宜的花生四稀酸 及—十一喊六稀酸之來源。總而言之,脂質含量可人、 4.4與6 g/100 kcal之間。脂質源中花生四烯酸:二一 丁一- 六稀酸之比例較佳係介於2 : 1與1 : 1之間。 該營養組合物亦可含有營養上有意義量之日常膳食所必 需的所有維生素及礦物質。某些維生素及礦物質已建立最 低需求。視情況存在於該營養組合物中之礦物質、維生素 及其他營養素的實例包括維生素A、維生素Βι、維生素 B2、維生素&、維生素Bu、維生素E、維生素κ、維生素 C、維生素〇、葉酸、肌醇、菸酸、生物素、泛酸、膽 鹼、鈣、磷、碘、鐵、鎂、銅、鋅、錳、氯化物、鉀、 鈉、硒、鉻、鉬、牛磺酸、及L_肉鹼。礦物質通常以鹽形 式加入。 若有必要’該營養組合物可含有如大豆卵磷脂、單_及 雙-檸檬酸甘油酯等之乳化劑與安定劑。尤其當該組合物 呈液體形式提供時。 該營養組合物可視情況含有具有有利效果的其他物質, 如’依餵養嬰兒之營養組合物中常用量之益生菌、纖維、 乳鐵蛋白、核苷酸、核苷等。 該營養組合物可依任何適宜方式製得。例如,使蛋白質 145394.doc 201032734 源、碳水化合物源及脂質源依適當比例混合在一起,製得 營養組合物。若使用乳化劑,可在此階段混入該混合物 中。此時可加入維生素與礦物質’但通常較遲加入,以避 免熱降解。可先將任何親脂性維生素、乳化劑等溶於脂肪 源中,然後混合。隨後可將水(較佳為經逆滲透之水)混合 於其中,形成液體混合物。 隨後可熱處理該液體混合物’從而減少細菌量。例如, •可將該液體混合物迅速加熱至約8〇°C與約not之間的溫 度,保持約5秒至約5分鐘。可藉由蒸汽注入或熱交換器 (例如板式熱交換器)進行。 隨後可將該液體混合物冷卻至約6〇〇c與約85t>c之間;例 如藉由閃蒸冷卻。隨後可例如以兩階段均質化該液體混合 物;第一階段約7 MPa至約40 MPa及第二階段約2 Mpa至 約14 MPa。隨後可將該經均質化的混合物進一步冷卻,並 可加入任何熱敏感性組份(如維生素與礦物質)。宜在此時 參調整該均質化混合物之pH與固形物含量至標準量。 若需要製得粉末狀組合物,將經均質化的混合物移至適 宜的乾燥裝置(如喷霧乾燥器或冷凍乾燥器)且轉變為粉 末。該粉末應具有少於約5重量%之含水量。 若需製得液體組合物’將經均質化的混合物填充至適宜 的容器(較佳無菌)中。然而,亦可在容器中殺菌該液體組 合物。適宜進行此填充性質之裝置可於市面上購得。該液 體組合物可呈固形物含量約i 0至約i 4重量。/〇之現成可德養 之組合物形式,或可呈濃縮物形式;通常其固形物含量為 145394.doc 201032734 約20至約26重量%。 現將參照以下實例進一步說明本發明。 實例1 以下出示根據本發明營養組合物之組成實例: 營養素 每 100 kcal 每公升 能量(kcal) 100 630 蛋白質(g) (脫脂奶粉, 經改質的甜乳清) 游離組胺酸(mg) 酪蛋白:乳清之比例 1.5 2.5 40:60 9.45 15.8 40:60 脂肪(g) 亞油酸ig) α·亞麻酸(g) DHA(mg) ARA(mg) 亞油酸:α-亞麻酸 5.3 1.0 0.5 11.5 11.5 2 33.4 6.6 3.3 72.5 72.5 2 乳糖(g) 11.6 73.1 礦物質及電解質 Na(mg) 25 158 K(mg) 89 561 Cl(mg) 64 403 Ca(mg) 64 403 P(mg) 32 202 Ca/P 2.0 2.0 Mg(mg) 6.9 43.5 Μη(μβ) 8.0 50.4 維生素及微量元素 維生素A(IU) 350 2205 維生素D(IU) 60 378 維生素E(IU) 1.2 7.6 維生素Κ1(μ8) 8.0 50.4 維生素C(mg) 10 63 維生素Bl(mg) 0.07 0.44 維生素B2(mg) 0.15 0.95 终酸(mg) 1.0 6.3 維生素B6(mg) 0.075 0.47 葉酸㈣ 12 75.6 泛酸(mg) 0.45 2.83 維生素Β12(μ8) 0.3 1.89 生物素(pg) 2.2 13.9 -10- 145394.doc 201032734 膽鹼(mg) 10 63 肌醇(mg) 5.0 31.5 牛磺酸(mg) 7.0 44.1 肉驗(mg) 1.6 10.1 Fe(mg) 1.2 7.56 ι_ 15 94.5 Cu(mg) 0.07 0.44 δβ(μβ) 2.0 12.6 Zn(mg) 0.75 4.72 核苷酸 CMP(mg) 2.3 14.5 UMP(mg) 1.5 9.5 AMP(mg) 0.7 4.4 GMP(mg) 0.3 1.9 可將根據本發明營養組合物作為唯一營養源餵養出生4 至6個月之嬰兒,隨後在引入固體食物期間作爲混合膳食 的一部分,直到約12月大時完全斷奶為止。 實例2 此實例研究將含不同量LA及ALA之膳食餵養新生幼天竺 鼠對斷奶後幼畜之總脂肪質量發展之影響。天竺鼠嬰兒被 認為係研究用於預測人類嬰兒脂肪質量發展之良好動物模 型,因爲如同新生人類嬰兒,新生幼天竺鼠天生具有顯著 φ 量的體脂肪量,而新生幼鼠則太痩。 研究設計: 將新生雄性天竺鼠分為三組,每組20隻動物。對每組餵 養哺乳/斷乳膳食21天,其中44%能量由脂肪提供。不同膳 食均呈等熱量,且僅ALA含量不同。高含量ALA膳食含有 以總脂肪酸計之10% ALA,中等含量ALA膳食含有以總脂 肪酸計之2·4°/α ALA及低含量膳食含有以總脂肪酸計之 0.85% ALA。膳食之間之LA含量保持相對恒定,以使 LA:ALA之比例分別為約2、10及30。表1進一步詳細出示 145394.doc • 11 - 201032734 三種飲食之脂肪酸組成。 表1 :哺乳/斷乳膳食之脂肪酸組成: 佔總脂肪酸之% 10% ALA 2.4% ALA 0.8% ALA C12:0 7.1 8.2 7.9 C14:0 3.4 3.9 3.7 C16:0 22.7 22.0 21.8 C16:l 0.2 0.1 0.1 C18:0 3.0 3.2 3.0 C18:l 33.5 33.0 33.3 C18:2n-6(LA) 20.2 26.2 28.5 C18:3n-3(ALA) 9.9 2.4 0.8 C20:0 0.0 0.0 0.0 C20:l 0.0 0.0 0.0 C20:4n-6 0.0 0.0 0.0 C20:5n-3 0.0 0.0 0.0 C22:0 0.0 0.0 0.0 C22:5n-3 0.0 0.0 0.0 C22:6n-3 0.0 0.0 0.0 LA/ALA 2.0 10.7 33.6 哺乳/斷乳期(第21天)結束時,對所有組餵以含有2〇/〇 ALA及26%LA之具有中度高脂肪含量(35%能量來自脂肪) 的膳食至第136天。於第21、51、79、107、128及136天記 錄體重及脂肪質量,並於第21及130天記錄腹膜後的脂肪 組織細胞結構、血漿脂肪酸組成、及胰島素。 ◎ 結果: 如期望,哺乳/斷乳期結束(第21天)時,1〇% Ala組之血 漿磷脂(表2)及甘油三酸酯(表3)部份中的ALA濃度均比其 他組高。 表2.第21天之血漿磷脂中脂肪酸(gg/ml)組成。平均值士平 均標準誤差 145394.doc •12· 201032734 高含量ALA 中等含量ALA 低含量ALA C10:0 0.1 ±0.02 0.1 ±0.03 0.1 ±0.07 C12:0 0.2 ± 0.03 0.2 ± 0.02 0.3 ±0.13 C14:0 0.8 ± 0.23 1.0±0.10 1.1 ±0.17 C16:0 35.9 ±9.1 49.3 士 8.9 40.2 ±3.6 C17:0 1.2 ±0.38 1.9 ±0.41 1.2 ±0.10 C18:0 70.1 ±23.6 98.6 ±28.1 68.6 ±4.2 C18:l n-9順式+反式 23.4 ±7.6 30.8 ± 7.3 23.2 ±1.9 C18:l n-7順式+反式 3.1 ±0.8 6.2 ± 1.4 5.2 ±0.9 Cl 8:2 n-6(LA) 67.5 ± 22.2 99.0 ± 26.3 77.0 ±7.5 C18:3n-6(GLA) 0.1 ±0.06 0.1 士 0.09 0.2 ±0.13 C18:3n-3(ALA) 2.9 ±1.8 0.9 ± 0.2 0.6 ± 0.2 C20:0 1.2 ±0.5 1.5 ±0.2 0.9 ± 0.03 C20:ln-9 0.5 ± 0.2 0.7 士 0.08 0.6 ±0.1 C20:2n-6 0.8 ±0.1 1.2 ±0.1 1.3 ±0.2 C20:3n-6 0.9 ± 0.2 1.1 ± 0.25 1.0 ±0.07 C20:4n-6(AA) 11.4 ±3.6 14.8 ±3.0 11.7±1.1 C20:3n-3 0.3 ± 0.08 0.2 ± 0.06 0.1 ± 0.03 C22:0 1.9 ±0.9 2.1 ± 0.4 1.1 ±0.2 C22:ln-9 h 0.4 ±0.2 h0.4±0.1 1.5± 1.0 C20:5n-3(EPA) 0.2 ±0.1 0.1 士 0.03 0.1 ±0.03 C22:2n-6 1.1 ±0.5 1.5 ±0.2 0.8 ±0.1 C22:4n-6 1.2 ±0.5 1.8 ±0.3 1·2 ± 0.2 C24:0 2.6 ± 1.2 卜3.4士0_6 1.9 ±0.4 C24:ln-9 2.4 ±0.8 2.8 土 0·3 2.0 ±0.5 C22:5n-3(DPA) 2_1 ±0.8 1.7 士 0.3 0.9 ±0.1 C22:6n-3(DHA) 1.1 ±0.4 [1.3 ±0.3 0.7 ±0.1 ❹ 表3:第21天之血衆甘油三酸醋中FA(pg/ml)組成。平均值 ±平均標準誤差 高含量ALA 中等含量ALA 低含量ALA C10-.0 0.2 ±0.1 0.1 ± 0.04 0.2 ± 0.01 C12:0 0.9±0_2 1.0±0.1 0.8 ± 0.3 Cl 4:0 4.0 ± 1.1 4.6 ±0.7 4.0 ± 2.4 C16:0 49.1 ± 10.7 52.8 ±5.7 42.2 ±18 C17:0 0.9 ± 0.2 1.1 ±0.2 0.7 ± 0.09 C18:0 15.7 ±3.3 14.4 士 2.3 10.5 ±3.5 C18:l n-9順式 85.0 ± 17.8 85.4 ±6.0 63.2 ±18 C18:l n-7順式 2.6 ± 0.5 2.8 ± 0.3 2.0 ± 0.6 Cl 8:2 n-6(LA) 72.8± 13.7 85.4 ±6.0 71.1 ±27.9 145394.doc -13· 201032734 C18:3n-6(GLA) 0.2 ±0.2 0.6 ± 0.05 0.5 ±〇.l C18:3n-3(ALA) ll.l±2.5a 5.1 ±0.7B 2.7 ± 0.2 b C20:0 0.5 ± 0.2 0.7 ±0.1 0.2 ±0.1 C20:ln-9 1.2±0·1 1.3 ±0.1 LΠ ±0.5 C20:2n-6 1.4 ±0.2 1.5 ±0.2 1.6 ±0.8 C20:3n-6 6.8 ±0.1 0.7 ± 0.09 0.6 ±〇.〇9 C20:4n-6(AA) 3.7 ± 0.4 3.5 ± 0.3 3.7 ±0.3 C20:3n-3 0.4 ±0.1 0.2 ± 0.05 0.1 ±0.09 C22:0 0.4 ± 0.04 0.4 ±0.05 0.3 ± 0.02 C22:ln-9 0.3 ± 0.08 0.2 ± 0.02 0.2 ± 0.03 C20:5n-3(EPA) 0.3 ± 0.04 0.1 ±0.04 0.1 ± 0.08 C22:2n-6 ~~—~~ 0.3 ± 0.04 0.3 ± 0.06 0.2 ± 0.08 C22:4n-6 6.9 ±0.1 0.9 ±0.1 0.9 ± 0.2 C24:0 0.7 ±0.1 0.8 ±0.1 0.6 ±0.1 C22:5n-3(DPA) 0.8 ±0.1 0.6 ±0.1 0.4 ±0.01 C22:6n-3(DHA)~~ 0.3 ±0.1 0.3 ± 0.06 0.2 ± 0.05 不同字母表示在ρ<0·05下具有統計顯著性;ND,不可 檢測 如圖1所示’實驗期間三組之間的平均體重並無顯著不 同。然而’圖2顯示,第21天至第78天期間,高含量ALA 組所增加體重少於其他組。 哺乳/斷乳期(21天)結束時,由NMR測定各組間之總脂肪 質量並無差異。然而’高含量ALA組之腹膜後脂肪組織之 脂肪細胞直徑平均值小於其他組(表4)。 表4 :脂肪細胞直徑。平均值±平均標準誤差 ,组 細胞直徑(μιη) 高含量 ALA 27.5 ± 0.8 中等含量ALA 31.1 ±1.5 低含量 ALA 31.9 ±1.7 高含量ALA組的直徑較大(3〇至50 μιη)之脂肪細胞數量 較少(表5)。 145394.doc •14- 201032734 表5 ··第21天時,每克腹膜後脂肪組織中每段直徑範圍内 之總細胞數量(χ1〇6)。平均值±平均標準誤差 細胞直徑 10% ALA 2.4% ALA 0.8% ALA 15-19 1.27 ±0.2 1.19 ±0.2 0.91 ±0_2 19-29 3·82± 0_6 3·70±0·5 3.68 ±0.8 30-39 2.18 ±0·4 3_54±0·2 4.43 ± 0.8 40-49 0.37 ±0·1 1.47 ±0.2 1.85 ±0.7 50-60 0.07 ± 0.02 0.34 ± 0.04 0.49 ±0.3 ❹ 有趣的是’觀察到勝食中大脂肪細胞(>40 μιη)數量盘 ALA百分比之間存在劑量-效應關係。自圖3可知,攝入 ALA越多,大脂肪細胞的數量越少。 出乎意料地,如圖4及5中所示,在第79天(p<〇 〇1)、第 107天(ρ<〇·〇1)及第128天(ρ=〇·〇8)時,低含量ALA組比高含 量ALA組具有更高之脂肪質量值(以克及百分比表示)。 於第21天時,各組間血漿胰島素濃度並無差異。然而, 如圖6所示,實驗結束時,低含量ALA組之血漿胰島素濃 φ 度約為其他兩組的1.5倍。圖7顯示,在胰腺胰島素含量方 面觀察到相似結果。當與高含量ALA組比較時(p=0 08), 低含量ALA組之胰腺胰島素含量約增加14倍。 此實例明確證明,於嬰兒期餵以富含ALA之膳食對脂肪 組織之漸進發展或印記扮演重要角色,此方式可降低日"後 對過度發展的感$,)·生。具體而•,其#果顯示哺乳/斷乳 期攝取具有高LA:ALA比例之低含量ALA會導致日後肥胖 及罹患咼胰島素▲症之趨勢增強。 實例3 145394.doc 201032734 此實例利用D20方法研究將含有不同量LA及ALA之膳食 餵養新生幼天竺鼠時,對脂肪組織細胞(AT-細胞)之增殖率 及脂肪重新合成(DNL)的影響。研究實例2之高含量ALA組 及低含量ALA組。每組10隻幼畜接受5天D20,然後在第21 天時處死。其他10隻幼畜接受5天D20,然後在第136天時 處死。於第一曰清晨經腹腔投與氘化水(經減菌的0.9% NaCl、99% D20,依35 mg/g體重)。然後,其餘5天内使幼 畜隨意飲用氘化水(富含8%氘)。隨後於異氟烷麻醉下藉由 放血法處死。將來自主動脈之血液收集於肝素化小瓶中 (最少200 μΙ〇。收集腹膜後、附睾及皮下脂肪組織及肝臟 以及來自後肢之骨髓,並於分析前保存在-80°C下。 先前已詳細論述分析步驟(Neese RA、Siler SQ、Cesar D、Antelo F、Lee D、Misell L、Patel K、Tehrani S、 Shah P、Hellerstein MK,「Advances in the stable isotope mass spectrometric measurement of DNA synthesis and cell proliferation」Analy Biochem 2001; 298: 189-195) ° 簡而 言之,自脂肪組織(約50 mg)提取AT細胞之基因組DNA及 甘油三酸酯(TG)。藉由聯結氣相層析之質譜儀(GC/MS, Hewlett-Packard,Palo Alto,CA)來確定DNA中的氘富集量 及來自TG之棕櫚酸酯。 以D20併入量計算DNA複製(細胞增殖)及DNL之用法係 基於前體-產物關係(Hellerstein MK,Neese R.「Mass isotopomer data analysis: a technique for measuring biosynthesis and turnover of polymers j Am J Physiol 1992; 145394.doc -16· 201032734 263: E988-E1001)。於此方法中,藉由定量有標記之DNA 股之比例來計算標記期間所發生之細胞***次數。以脂肪 DNA中之EM1(同位素過量富集)除以(標準化)骨髓DNA中 之EM1,計算脂肪組織細胞之增殖速率分率(FSR細胞,以 新細胞%/5天計)。使用骨髓富集量估算每一隻動物可達到 之最大DNA富集量。 利用質量同位素分佈分析(MIDA),由來自水併入TG-棕 φ 櫚酸酯之標記氘計算TG中之DNL或「棕櫚酸酯合成速率分 率」(FSR棕櫚酸酯,以新棕櫚酸酯%/5天計)。基於所測定 的體内水份富集量,計算棕櫊酸酯中可達到之最大氘富集 量(計算方法詳述於Hellerstein MK及Neese RA之「Mass isotopomer distribution analysis at eight years: theoretical, analytic, and experimental considerations」 Am J Physiol 1999; 276: E1146-E1170 中)。 結果 〇 脂肪組織及肝臟重量概述於表6中。 表6 :第21及第136天之脂肪組織(AT)及肝臟重量(以g計)。 組 肝臟 附睾AT* 腹膜後AT 第21天 高含量ALA 8.57 ±0.54 0.15 ±0.02 0.56 ±0.14 低含量ALA 7.09 ± 0.40 0.09 ±0.01 0.38 ± 0.06 第136天 高含量ALA 29.73 ±2.15 8.09 ± 1.55 3 9.36 ± 1.21 低含量ALA 30.10± 1.11 10.94 ± 0.58 b 10.98 ±0.54 不同字母表示在P<〇.05下具有統計顯著性。 145394.doc 17 201032734 *第136天時,高/低含量Ala組之間P=〇.020 表7中概述早期膳食處理對脂肪堆積物中細胞合成速率 分率(FSR或增殖速率分率)之影響^ AT-細胞包括諸如全部 脂肪組織的脂肪細胞及基質血管細胞(前-脂肪細胞、腸上 皮細胞、巨噬細胞等)之所有類型細胞。 表7:第21及第136天之FSR(以新細胞%/5天計) 組 皮下AT* 附睾AT 腹膜後AT 第21天 高含量ALA 8.9 ±8.7 13.5 ±2.0 5.3 ± 2.3 低含量ALA 18.7 ± 13.7 15.0 ±4.1 3.3 ± 0.7 第136天 高含量ALA 8.6 ± 1.7* 7.7 ± 1.3 4.0 ± 0.6 低含量ALA 15.2 ± 1.3b 7.8 ±2.6 7.9 ±2.3 不同字母表示在P<0.05下具有統計顯著性 * :第136天時,高/低含量ALA組之間P=0.021 此等結果顯示’與高含量ALA組比較,低含量ALA組 中’第136天時(Ρ=〇·〇21)皮下脂肪組織之細胞增殖速率較 高(雙倍)及腹膜後細胞增殖較快(但不明顯),但附睾脂肪 組織之細胞增殖未變化。因皮下脂肪組織係成年天竺鼠全 身之主要脂肪堆積物,故於此脂肪組織中細胞增殖加快可 解釋攝取低含量ALA後所觀察到的脂肪質量組合物增加 (於實例2中獲得的結果)的原因。在機轉上,該等結果顯示 低含量ALA組中之體脂肪質量增加與成年後期天竺鼠中脂 肪組織細胞增殖速率(過度增生)提高有關。 攝取低含量ALA不會改變脂肪堆積物中之脂肪重新合成 145394.doc • 18 - 201032734 (DNL·),但於第21日,發現低含量ALA組之肝臟DNL·高於 高含量ALA 組(P<0.001)(表 8)。 表8:第21及第U6日之DNL(以新棕櫚酸酯%/5天計) 組 肝臟 皮下AT 附睾AT 腹膜後AT 第21曰 高含量ALA 8.8±2.6a 9.3 ±6.6 14.9 ±2.8 13.8 ±5.4 低含量ALA 17.4 士 3.7b 2.2 ± 1.8 17.1 ±2.5 12.9 ±2.3 第136日 高含量ALA 5.7 ± 0.6 1.87 ±0.26 1.18 ±0.16 1.40 ±0.39 低含量ALA 5.6 ± 0.4 1.29 ±0.18 0.92 ±0.12 1.06 ±0.07 不同子母表不在P<0.001下之統計顯著性。 此實例3顯示,於哺乳/斷乳期攝取低含量ALA會提高出 生21天的天竺鼠之肝臟DNL之速率,及提高成年天竺鼠之 皮下脂肪組織之細胞增殖速率。 【圖式簡單說明】 圖1顯示餵以不同膳食的三組幼天竺鼠於出生頭136天内 φ 之體重變化; 圖2顯示三組幼畜在第21天與第79天期間所增加的體重 中位值; 圖3顯示與ALA攝取量成函數關係之巨大脂肪細胞的數 量圖; 圖4顯示第21天至第128天期間三組脂肪質量之變化(以 克計); 圖5顯示三組於第79天、第i〇7天及第128天之脂肪質量 變化(以佔總體重之百分比表示); 145394.doc •19- 201032734 圖6顯示三組於第136天之平均血漿胰島素濃度;及 圖7顯示三組於第136天之胰腺胰島素含量。 145394.doc 20·
Claims (1)
- 201032734 七、申請專利範圍: 1. 一種營養組合物,其包含一種蛋白質源、一種脂質源及 一種碳水化合物源,其中以佔總脂肪酸含量之百分比表 示,該脂質源分別包含至少i 6重量%亞油酸及至少2重量 % α-亞麻酸,且其含量可使亞油酸:心亞麻酸之比例介 於1至10之間。 2. 3. 如凊求項1之營養組合物,其中該亞油酸含量係總脂肪 酸之18至300/〇。 如明求項1或2之營養組合物,其中該亞油酸含量係總脂 肪酸之18至25%。 4.如叫求項1或2之營養組合物,其中該…亞麻酸含量係總 脂肪酸之2至12%,更佳係6至11%。 5·如請求項1或2之營養組合物,其中該α-亞麻酸含量係總 脂肪酸之6至11 %。 6. 如明求項1或2之營養組合物,其中亞油酸:α亞麻酸之 參 比例較佳係介於2與6之間。 7. 一種以亞油酸及α-亞麻酸於製造如請求項丨至6中任一項 之營養組合物上之用途,供投與出生6個月内之嬰兒, 從而降低日後罹患肥胖症風險。 8. —種以如請求項丨至6中任一項之組合物於製造用於嬰兒 之營養組合物從而降低日後罹患肥胖症或超重之風險上 之用途’該組合物係計畫投與出生頭幾個月的嬰兒。 9. 如吻求項7或8之用途,其中該嬰兒係幼嬰寵物如狗或 書苗0 145394.doc 201032734 10如凊求項7之用途,其中該降低日後罹患肥胖症之風險 之特徵在於與未接受該組合物之對照群體比較,脂肪質 量在統計上顯著下降。 11 ·如請求項7之用途,其中該降低曰後罹患肥胖症之風險 之特徵在於此等風險在人類嬰兒之肥胖反彈年齡(如5歲 後)時明顯降低。 145394.doc
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