纯鱼油与天然鱼油相比：EPA和DHA的含量较高、安全性较低

　　鱼油脂肪乳富含二十碳五烯酸（EPA）与二十二碳六烯酸（DHA），可补充必需脂肪酸，改善全肠外营养患者的全身炎症，预防和治疗肠外营养相关肝病（PNALD）。

　　目前欧洲药典中有2个鱼油专利产品：天然鱼油（NFO）和纯鱼油（PFO），其EPA和DHA的总含量分别高达30%和45%。

　　波士顿儿童医院、麻省（马萨诸塞州）总医院、贝斯以色列女执事医疗中心通过对小鼠进行研究，发现静脉注射PFO后5分钟内出现呼吸急促和昏睡，处死后可见脾肿大，肝脾均可见富含脂肪的巨噬细胞。

　　因此，虽然PFO含有较高的EPA和DHA，但是静脉注射的耐受性差，导致终末器官损伤，可能并不安全。

JPEN J Parenter Enteral Nutr. 2016;40(4):118-119.

A Comparison of Fish Oil Sources for Parenteral Lipid Emulsions in a Murine Model.

Fell G, Cho B, Pan A, Nose V, Anez-Bustillos L, Dao D, Baker M, Nandivada P, Gura K, Puder K.

Boston Children's Hospital, Boston, MA, USA; Massachusetts General Hospital, Boston, MA, USA; Beth Israel-Deaconess Medical Center, Boston, MA, USA.

PURPOSE: Lipids in parenteral nutrition (PN) are administered as an emulsion of oil dispersed in an aqueous medium. They are important for preventing essential fatty acid deficiency, and they provide noncarbohydrate calories to prevent fatty liver disease that can result from high-carbohydrate feeding. Parenteral fat is also important in managing PN-associated liver disease (PNALD), a complication of long-term PN characterized by cholestasis and hepatic inflammation that can progress to cirrhosis and death if not treated. Fish oil (FO) lipid emulsions can reverse PN-induced cholestasis. FO is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—polyunsaturated omega-3 fatty acids that help prevent essential fatty acid deficiency and that are precursors of anti-inflammatory mediators that may contribute to treating PNALD. There are 2 FO monographs in the European Pharmacopeia. One is "Fish oil, rich in omega-3 fatty acids," or natural FO (NFO), in which EPA and DHA constitute up to 30% of the fatty acids and virtually all fatty acids are in triglyceride form. The other is "Omega-3 acid triglycerides," or purified FO (PFO), in which EPA and DHA constitute at least 45% of the fatty acids and the oil is a mixture of mono-, di-, and triglycerides. Use of PFO, by virtue of its high concentration of EPA and DHA, may be beneficial as compared with NFO, but use of intravenous (IV) emulsions containing PFO has not been previously reported. The purpose of this study is to compare the effects of IV lipid emulsions made with NFO or PFO in a murine model.

METHODS: In the laboratory, lipid emulsions were generated containing different oils: United States Pharmacopeia–grade soybean oil (SO), NFO, or PFO. NFO and PFO met pharmacopeia standards of their respective monographs. All emulsions contained 20% oil in an aqueous dispersion (12% egg phospholipid, 2.5% glycerol, 0.03% sodium oleate). Emulsions underwent PFAT5 and mean globule size analysis at a commercial laboratory (Micro Measurements, Wheeling, IL). Chow-fed C57BL/6 mice received saline, one of the above emulsions, or a commercial FO (Omegaven [OM]; Fresenius Kabi, Bad Homburg, Germany) by tail vein injection (2.4 g/kg/d) for 19 days. Effects after each dose were recorded. On day 19, animals were euthanized, and livers, spleens, and lungs were procured and fixed in 10% formalin for histologic analysis.

RESULTS: All emulsions met the United States Pharmacopeia standard for mean globule size, and all except the NFO emulsion met the PFAT5 standard (NFO PFAT5 = 0.057). Animals administered OM, SO, and NFO tolerated injections well. Those administered PFO developed tachypnea and lethargy for ~5 minutes following injection. At euthanasia, PFO-treated animals had splenomegaly as compared with the other groups. On histologic analysis, the PFO groups had splenic fat-laden macrophages and hepatic sinusoidal lipid-laden Kupffer cells with no inflammation or necrosis. Lungs in this group had scattered fat deposits. All other groups had histologically normal livers, spleens, and lungs.

CONCLUSIONS: Use of PFO lipid emulsions is an attractive possibility for improving systemic inflammation in PN-dependent patients and optimizing management of PNALD. However, oils containing PFO were poorly tolerated and resulted in adverse end-organ sequelae. The presence of fat-laden macrophages in livers and spleens suggests attempts to clear physiologically incompatible fat molecules. Although PFO may meet pharmacopeia standards, it may not be safe for use in IV lipid emulsions, even when fatty acids in nontriglyceride form are present in small amounts.

FINANCIAL SUPPORT: BASF, Boston Children's Hospital Surgical Foundation, National Institutes of Health grant F32DK104525-01.