A 40-year-old, lean (body mass index 24.8) Asian woman with gestational diabetes presents to the emergency room at 24 weeks gestation with nausea and epigastric pain. Amylase and lipase are elevated as are triglycerides at 3,800 mg/dl, and she is diagnosed with acute pancreatitis. An abdominal ultrasound is negative for gallstones or any pathology of the gallbladder or biliary ducts.
She is admitted to the intensive care unit and remains NPO for the first 24 hours and is treated with intravenous fluids, pain medications, and gemfibrozil, after which a very low-fat diet was added. These treatments result in a subsequent decrease in triglycerides to 437 mg/dl. Glucose levels remain less than 125 mg/dl throughout the hospitalization.
Following discharge, she adheres to the low-fat diet, but discontinues gemfibrozil over concerns of potential harm to the fetus. She is seen in the lipid clinic at 29 weeks gestation, at which time the triglyceride level was 1,225 mg/dl. She has no abdominal discomfort and no eruptive xanthomas. She is advised to continue adhering to a diet that contained no more than 40 grams of fat per day, to take a prescription omega-3 fatty acid (icosapent ethyl esters) 2 grams twice daily, and to use medium chain triglyceride (MCT) oil three times per day. Both the patient and her husband initially agree with these recommendations; however, she ultimately decides not to take the omega-3 fatty acid or MCT oil due to concerns for the fetus.
She presents to the hospital at 32 weeks gestation with severe abdominal pain and is diagnosed with preeclampsia, placental abruption, and fetal demise. Following delivery, she develops a coagulopathy and requires multiple blood products. Triglycerides are 1,200 mg/dl, and gemfibrozil is restarted. Upon discharge, she stops the gemfibrozil and restarts the omega-3 fatty acid.
At a follow-up lipid clinic visit, she and her husband receive extensive counseling regarding her genetic predisposition to hypertriglyceridemia and the importance of adherence to the recommended treatments that included use of a fibrate, prescription omega-3 fatty acids, MCT oil, a low-fat diet, and regular physical activity. A lipid profile is obtained after 4 weeks of uninterrupted treatment and showed: total cholesterol 177 mg/dl, triglycerides 256 mg/dl, high-density lipoprotein (HDL-C) 34 mg/dl, LDL-C 92 mg/dl, and apolipoprotein B 93 mg/dl.
Her 7-year-old son has not had lipids tested, and her family history is unknown.
When considering omega-3 fatty acid usage in this patient, all of the following are TRUE, with the exception of:
Show Answer
The correct answer is: C. Over-the-counter fish oil formulations are acceptable substitutions for the prescription omega-3 fatty acids in individuals at high risk for pancreatitis.
Answer option A is true. Prescription omega-3 fatty acids contain a combination of EPA and DHA, or EPA alone. They suppress hepatic lipogenesis and enhance fatty acid oxidation and may directly stimulate lipoprotein lipase to enhance removal of triglyceride-rich lipoproteins.1,2 Although they can be used as monotherapy, they are most often used in conjunction with other lipid-altering medications, such as fibrates or niacin, along with a low-fat diet and physical activity.3 Although they have been assigned as Category C by the US Food and Drug Administration, they are used during pregnancy when the benefits outweigh the potential risks and, to date, have not been found to have adverse effects on the mother or fetus.4,5
Answer option B is true. Despite the known inhibition of platelet aggregation, with bleeding times increased up to 1.5 times, clinically significant bleeding generally does not increase with the use of omega-3 fatty acids and has not been associated with increased risk of intraoperative or postoperative bleeding. Many clinical studies show that bleeding does not increase even during hospitalization for myocardial infarction when potent anticoagulants are used.6,7,8,9
Answer option C is false. Dietary fish oil supplements are not subject to the same regulatory standards or manufacturing oversight used by the FDA with prescription products, and thus, the efficacy, quality, and safety of the dietary supplements are open to question. Prescription omega-3 fatty acids reduce triglycerides more effectively and have greater bioavailability than dietary supplements. There may be considerable variability in the amount of omega-3 content in the dietary supplements, requiring the consumption of substantially more pills to achieve clinically appropriate doses. The prescription omega-3 fatty acids are consistent in their content and highly purified, reducing the potential to undergo oxidation and the risk of exposure to environmental toxins.9
Answer option D is true. The MARINE study showed that DHA and EPA have different effects on low-density lipoprotein (LDL-C) as well as lipoprotein particle concentration. LDL clearance is affected by its oxidative state, with oxidized LDL not being cleared. EPA is an inhibitor of lipid oxidation, whereas DHA is not; therefore, it is believed that EPA enhances clearance of LDL-C.10 While the potential exists for elevation in LDL-C with the use of DHA/EPA combinations, this does not appear to have a significant clinical impact. Should the LDL-C rise, adjustments can be made in other lipid-lowering agents to accommodate for the small increase.
The omega-3-acid ethyl esters and omega-3 –carboxylic acids (Epanova) contain both DHA and EPA, whereas icosapent ethyl esters contain only EPA.11,12
Answer option E is true. Throughout a normal pregnancy, total fat should be 20% to 35% of the total kcal. For a woman at risk or who has had acute pancreatitis of pregnancy, fat consumption should be approximately 20% of the total kcal, with this patient's requirement of 37 grams of fat per day.14
References
Bays HE, Tige AP, Sadovsky R, Davidson MH. Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms and clinical implications. Expert Rev Cardiovascular Ther 2008:6:391-409.
Bays HE, Ballantyne CM, Kastelein JJ, et al. Eicosapentaenoic acid ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, placebo-controlled, randomized, double-blind, 12-233k study with an open-label extension (MARINE) trial). Am J Cardiol 2011;108:682-90.
Van Heyningen C, Cozma I, Malani A. Lipoprotein-lipase deficiency: treatment with omega-3 fatty acids and colestyramine for severe gestational hypertriglyceridemia and follow up over twenty years. IntJ Case Reports Med 2013;2013:810803.
Omega-3 acid esters (lovaza) product package insert. GlaxoSmthKline; Research Triangle Park, ND. November 2008.
Parkinson AJ, Cruz Al, Heyward WL, Bulkow L. Elevated concentrations of plasma polyunsaturated fatty acids among Alaskan Eskimos. J Clin Nutr 1994: 59:384-8.
Erez I, Kowalczyk A, Liu H. The Effect of Fish Oil on Hemostasis and Coagulation During Cardiac Surgery (SCA Bulletin website). Available at: http://www.scahq.org/sca3/newsletters/2013apr/diu.html. Accessed on 3/4/2016.
Salisbury A, Harris W, Amin AP, Reid KJ, O'Keefe JH Jr, Spertus JA.. Relation between red blood cell omega-3 fatty acid index and bleeding during acute myocardial infarction. Am J Cardiol 2012;109:13-18.
Meredith DS, Kepler CK, Huang RC, et al. The effect of omega-3 fatty acid supplements on perioperative bleeding following posterior spinal arthrodesis. Eur Spin J 2012;21:2659-63.
Bays HE, Tige AP, Sadovsky R, Davidson MH. Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms and clinical implications. Expert Rev Cardiovascular Ther 2008;6:391-409.
Bays H, Braekman R, Ballantyne C, et al. Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on lipoprotein particle concentration and size in patients with very high triglyceride levels (the MARINE study). J Clin Lipidol 2012;6:565-72.
Bradberry J, Hilleman D. Overview of omega-3 acid therapies. Pharm Ther 2013;38:681-91.
Epanova product package insert. Astra Zeneca; Wilmington, Delaware. Oct 2014.
Practice Paper of the Academy of Nutrition and Dietetics: Nutrition and Lifestyle for a Healthy Pregnancy Outcome, July 2014.
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