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Essential Fatty Acids

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Essential Fatty Acids Essential Fatty Acid Deficiency Kris M. Mogensen, MS, RD, LDN, CNSC Team Leader Dietitian Brigham and Women’s Hospital Instructor Boston University College of Health and Rehabilitation Sciences: Sargent College [email protected] November 13, 2015 Disclosures • I will discuss “off label” use of a product • I will discuss “novel” lipid emulsions Objectives • Identify three patient populations at risk for essential fatty acid deficiency (EFAD) • Interpret biochemical measures of fatty acids to determine presence/absence of EFAD • Identify two interventions to prevent or treat EFAD Overview • Role of essential fats in the body • Risk factors for EFAD • Drug shortages and EFAD • Clinical manifestations & evaluation process • Treatment • Case study • Conclusion Overview • Role of essential fats in the body • Risk factors for EFAD • Drug shortages and EFAD • Clinical manifestations & evaluation process • Treatment • Case study • Conclusion Role of Fat in the Body • Major source of energy & energy storage • Cushioning/insulation • A means to absorb fat-soluble vitamins • Cell membranes • Inflammatory mediators/cell signaling systems • Creation of steroid hormones Impact of Fatty Acid Exposure on Cell and Tissue Responses From Calder PC. Functional roles of fatty acids and their effects on human health. JPEN 2015;39:18S-32S Essential Fatty Acids • Cannot be synthesized in the body • Two major EFAs: – Alpha-linolenic acid (omega-3) – Linoleic acid (omega-6) Fatty Acids Created from EFA *EFA Hamilton C et al. Essential fatty acid deficiency in human adults during parenteral nutrition. Nutr Clin Pract. 2006;21:387- 394 Overview • Role of essential fats in the body • Risk factors for EFAD • Drug shortages and EFAD • Clinical manifestations & evaluation process • Treatment • Case study • Conclusion Risk Factors for EFAD • Malabsorptive disorders – Crohn’s disease – Chronic pancreatitis – Cystic fibrosis – Short-bowel syndrome Sites of Absorption From Krause, 12th edition Prevalence of essential fatty acid deficiency in patients with chronic gastrointestinal disorders. Siguel EN and Lerman RG. Metabolism. 1996;45:12-23 • 47 patients with chronic intestinal disease – 25 Crohn’s disease – 11 UC – 4 Celiac – 7 Short-bowel syndrome • 56 healthy controls • Blood samples analyzed for fatty acids and triene:tetraene ratio Prevalence of essential fatty acid deficiency in patients with chronic gastrointestinal disorders. Siguel EN and Lerman RG. Metabolism. 1996;45:12-23 Prevalence of essential fatty acid deficiency in patients with chronic gastrointestinal disorders. Siguel EN and Lerman RG. Metabolism. 1996;45:12-23 Essential fatty acid deficiency in patients with severe fat malabsorption. Jeppesen PB et al. AJCN. 1997;65:837-843 • 112 patients with GI disorders – 66 Crohn’s disease – 26 UC – 16 bowel resection for varying reasons – 2 celiac disease – 1 radiation enteritis – 1 cholestatic liver disease • All had fecal fat analyzed • Blood analyzed for fatty acids • Stratified by % of fat malabsorption Essential fatty acid deficiency in patients with severe fat malabsorption. Jeppesen PB et al. AJCN. 1997;65:837-843 Degree of % with EFAD based Malabsorption on LA levels <10% 0% (n=52) 10-25% 5% (n=21) 25-50% 38% (n=24) >50% 67% (n=15) Risk Factors for EFAD • Carnitine deficiency – Necessary for metabolism of fat in the mitochondria – Required component for phospholipid remodeling and biosynthesis • Part of cell membranes! – Reservoir for long-chain fatty acids that will eventually be incorporated into cell membranes Carnitine Shuttle CPT-I, carnitine palmitoyltransferase-1; CPT-II, carnitine palmitoyltransferase-2; CACT, carnitine acylcarnitine translocase; CrAT, carnitine acetyl transferase; OMM, outer mitochondrial membrane; IMM, inner mitochondrial membrane. From Sharma & Black Drug Discov Today Dis Mech. 2009 From: Mogensen KM and Pfister DP. Carnitine supplementation: an update. Support Line. 2013;35:3-9 Risk Factors for EFAD • Patients with limited fat intake/delivery – PN-dependent patients with hypertriglyceridemia – Allergy to intravenous fat emulsion – Ultra-low fat diets – Possibly extracorporeal membrane oxygenation (ECMO) patient receiving PN • Will you be allowed to give IVFE? – (that’s a whole ‘nother talk) Essential fatty acid deficiency in four adult patients during total parenteral nutrition. Richardson TJ and Sgoutas D. AJCN. 1975;28:258-263 Essential fatty acid deficiency during total parenteral nutrition. Barr LH et al. Ann Surg. 1981;193:304-311 Diet-induced essential fatty acid deficiency in ambulatory patient with type I diabetes mellitus. Piper CM et al. Diabetes Care. 1986;9:291-293 43 y.o. M who followed a 7% fat diet for 4 months. Developed lethargy, fatigue, and a dry, scaly rash… Risk Factors for EFAD • National shortages of intravenous fat emulsion Anybody have any lipids to spare? Overview • Role of essential fats in the body • Risk factors for EFAD • Drug shortages and EFAD • Clinical manifestations & evaluation process • Treatment • Case study • Conclusion Drug Shortages • A major problem over the past 5 years – Intermittent shortages occurring for > 15 years • As of 2/28/2013 there were 324 medications in shortage – 70% were sterile injectables Data from: http://www.nutritioncare.org/Professional_Resources/Drug_Shortages_Update/#Why_do_drug_shortages_occur accessed 9/28/2015 Nutrition Support Drug Shortages • IV multivitamins, individual vitamins • IV multiple trace elements & individual trace elements • Individual electrolytes • Macronutrients (resolved…for now) – Intravenous fat emulsion – Various amino acid preparations IVFE Shortage • Still in shortage when I was preparing this talk in 2014 • Things are better… From http://www.nutritioncare.org/public-policy/product-shortages/ accessed 9/28/2015 A.S.P.E.N. Guidelines • Rationing guidelines include reserving IVFE for neonates and pediatric patients • For non-malnourished adults, or those with mild or moderate malnutrition, hold IV fat for the first two weeks of PN • Provision of 100g fat total/week after the first two weeks of PN • Also available at: http://www.nutritioncare.org/Professional_Resources/Drug_Short ages/PN_IV_Fat_Emulsions_Product/ Overview • Role of essential fats in the body • Risk factors for EFAD • Drug shortages and EFAD • Clinical manifestations & evaluation process • Treatment • Case study • Conclusion Physical Signs and Symptoms of EFAD • Dermatitis – Dry, scaly rash • Hair loss • Poor wound healing • Impaired growth in children Essential fatty acid deficiency in adults receiving total parenteral nutrition. Fleming CR et al. AJCN. 1976;29:976-983 Essential fatty acid deficiency in surgical patients. O’Neill JA et al. Ann Surg. 1977;185:535-541 Essential Fatty Acid Deficiency in a Severely Malnourished Patient Receiving Parenteral Nutrition. Duerksen D and McCurdy K. Diges Dis Sci 2005;12:2386-2388 Essential Fatty Acid Deficiency in a Child http://images.medscape.com/pi/editorial/cmecircle/2002/1819/hansen/slide17.jpg accessed 2/16/06 Be careful of look-alikes! Physical Signs and Symptoms of EFAD • Correlate physical exam with clinical history – Limited fat intake only? – Other potential causes of a similar rash? • Zinc deficiency alone, or superimposed on EFAD? • Other causes of skin rash Other Signs and Symptoms of EFAD • Fatty liver • Elevated liver function tests • Hyperlipidemia • Hemolytic anemia • Thrombocytopenia • Reduced platelet aggregation • Increased susceptibility to infection Biochemical Evaluation • Evaluate the triene:tetraene ratio – Why? – Mead acid (triene acid) production is increased and linoleic and arachidonic acid are decreased – Triene:tetraene ratio evaluates the mead:arachidonic acid ratio – If > 0.4 (some references suggest 0.2), the patient has EFAD Timeframe of EFAD Development • Typical EFAD onset occurs after 4 weeks of fat-free PN • Other reports have shown earlier onset of 10-20 days • Most of EFAD is associated with linoleic acid deficiency; few reports of alpha-linolneic acid deficiency Overview • Role of essential fats in the body • Risk factors for EFAD • Drug shortages and EFAD • Clinical manifestations & evaluation process • Treatment • Case study • Conclusion Treating Deficiency • Prevent when you can! – Provide at least 10% of energy from polyunsaturated fats – 2%-4% of total calories should be from linoleic acid Treating Deficiency • For PN-Dependent patients – The main IVFE available is Intralipid – 50% of the fat content is linoleic acid – To give 10g linoleic acid, you must give 20g fat total Comparison of IV Fat Emulsions Concentration 10% 20% 30% kcal/mL 1.1 2 2.9 Fat g/L (9.3 kcal/g) 100 200 300 Phospholipid g/L (6 kcal/g) 12 12 12 Glycerol g/mL (4.2 kcal/g) 22.5 22.5 17 Example: 250 mL 20% IVFE = 500 kcals, 50 g fat (25 g as linoleic acid), 3 g phospholipid, 5.625 g glycerol Parenteral fat does NOT provide 10 kcal/gram! Treating Deficiency • For patients taking an oral diet, encourage high intake of oils rich in essential fats • Encourage fatty fish or omega-3 fatty acid supplements Oil Linoleic acid (g/tbsp) Safflower 1.73 Canola 2.61 Sunflower 3.904 for mid-oleic (? up to 8.9) Soybean 6.857 http://ndb.nal.usda.gov/ndb/nutrients/report?nutrient1=675&nutrient2=&nutrient3=&fg=4&max=25&subset=0&offset=50&sort= f&totCount=76&measureby=m accessed 9/28/2015 Use of Topical Oils • There is some cutaneous absorption of essential fats • The question: is that absorption adequate? Orphan baby elephants after coconut oil rubdown! https://www.sheldrickwildlifetrust.org/asp/gallery_zoom.asp?Name=/keepers_diary/3420117121-
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