Essential Fatty Acid Deficiency

Size: px

Start display at page:

Download "Essential Fatty Acid Deficiency"

Harry Stephens
5 years ago
Views:

1 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 kmogensen@partners.org November 13, 2015

2 Disclosures I will discuss off label use of a product I will discuss novel lipid emulsions

3 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

4 Overview Role of essential fats in the body Risk factors for EFAD Drug shortages and EFAD Clinical manifestations & evaluation process Treatment Case study Conclusion

5 Overview Role of essential fats in the body Risk factors for EFAD Drug shortages and EFAD Clinical manifestations & evaluation process Treatment Case study Conclusion

6 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

7 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

8 Essential Fatty Acids Cannot be synthesized in the body Two major EFAs: Alpha-linolenic acid (omega-3) Linoleic acid (omega-6)

9 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:

10 Overview Role of essential fats in the body Risk factors for EFAD Drug shortages and EFAD Clinical manifestations & evaluation process Treatment Case study Conclusion

11 Risk Factors for EFAD Malabsorptive disorders Crohn s disease Chronic pancreatitis Cystic fibrosis Short-bowel syndrome

12 Sites of Absorption From Krause, 12 th edition

13 Prevalence of essential fatty acid deficiency in patients with chronic gastrointestinal disorders. Siguel EN and Lerman RG. Metabolism. 1996;45: 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

14 Prevalence of essential fatty acid deficiency in patients with chronic gastrointestinal disorders. Siguel EN and Lerman RG. Metabolism. 1996;45:12-23

15 Prevalence of essential fatty acid deficiency in patients with chronic gastrointestinal disorders. Siguel EN and Lerman RG. Metabolism. 1996;45:12-23

16 Essential fatty acid deficiency in patients with severe fat malabsorption. Jeppesen PB et al. AJCN. 1997;65: 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

17 Essential fatty acid deficiency in patients with severe fat malabsorption. Jeppesen PB et al. AJCN. 1997;65: Degree of Malabsorption <10% (n=52) 10-25% (n=21) 25-50% (n=24) >50% (n=15) % with EFAD based on LA levels 0% 5% 38% 67%

18 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,

19 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

20 From: Mogensen KM and Pfister DP. Carnitine supplementation: an update. Support Line. 2013;35:3-9

21 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)

22 Essential fatty acid deficiency in four adult patients during total parenteral nutrition. Richardson TJ and Sgoutas D. AJCN. 1975;28:

23 Essential fatty acid deficiency during total parenteral nutrition. Barr LH et al. Ann Surg. 1981;193:

24 Diet-induced essential fatty acid deficiency in ambulatory patient with type I diabetes mellitus. Piper CM et al. Diabetes Care. 1986;9: y.o. M who followed a 7% fat diet for 4 months. Developed lethargy, fatigue, and a dry, scaly rash

25 Risk Factors for EFAD National shortages of intravenous fat emulsion Anybody have any lipids to spare?

26 Overview Role of essential fats in the body Risk factors for EFAD Drug shortages and EFAD Clinical manifestations & evaluation process Treatment Case study Conclusion

70% were sterile injectables Data from: http://www.nutritioncare.

27 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: accessed 9/28/2015

28 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

29 IVFE Shortage Still in shortage when I was preparing this talk in 2014 Things are better

30 From accessed 9/28/2015

31 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: ages/pn_iv_fat_emulsions_product/

32 Overview Role of essential fats in the body Risk factors for EFAD Drug shortages and EFAD Clinical manifestations & evaluation process Treatment Case study Conclusion

33 Physical Signs and Symptoms of EFAD Dermatitis Dry, scaly rash Hair loss Poor wound healing Impaired growth in children

34 Essential fatty acid deficiency in adults receiving total parenteral nutrition. Fleming CR et al. AJCN. 1976;29:

35 Essential fatty acid deficiency in surgical patients. O Neill JA et al. Ann Surg. 1977;185:

36 Essential Fatty Acid Deficiency in a Severely Malnourished Patient Receiving Parenteral Nutrition. Duerksen D and McCurdy K. Diges Dis Sci 2005;12:

Essential Fatty Acid Deficiency in a Child http://images.medscape.

37 Essential Fatty Acid Deficiency in a Child accessed 2/16/06

38 Be careful of look-alikes!

39 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

40 Other Signs and Symptoms of EFAD Fatty liver Elevated liver function tests Hyperlipidemia Hemolytic anemia Thrombocytopenia Reduced platelet aggregation Increased susceptibility to infection

arachidonic acid are decreased Triene:tetraene ratio evaluates the

41 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

42 Timeframe of EFAD Development Typical EFAD onset occurs after 4 weeks of fat-free PN Other reports have shown earlier onset of days Most of EFAD is associated with linoleic acid deficiency; few reports of alpha-linolneic acid deficiency

43 Overview Role of essential fats in the body Risk factors for EFAD Drug shortages and EFAD Clinical manifestations & evaluation process Treatment Case study Conclusion

44 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

45 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.

46 Comparison of IV Fat Emulsions Concentration 10% 20% 30% kcal/ml Fat g/l (9.3 kcal/g) Phospholipid g/l (6 kcal/g) Glycerol g/ml (4.2 kcal/g) Example: 250 ml 20% IVFE = 500 kcals, 50 g fat (25 g as linoleic acid), 3 g phospholipid, g glycerol Parenteral fat does NOT provide 10 kcal/gram!

47 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 for mid-oleic (? up to 8.9) Soybean f&totcount=76&measureby=m accessed 9/28/2015

gallery_zoom.asp?name=/keepers_diary/3420117121- pic2.

48 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! pic2.jpg&s=keepers&caption=orphans%20after%20being%20rubbed%20down%20in%20coconut%20oil&id=9047

49 Correction of the cutaneous manifestations of essential fatty acid deficiency in man by application of sunflower-seed oil to the skin. Prottey C. et al J Invest Dermatol 1975;64: patients with short bowel syndrome and known EFAD 7 controls on an unrestricted diet Intervention: 250 mg sunflower seed oil applied to the R arm 250 mg olive oil applied to the L arm Measured Various skin surface lipids Day 4, 8, 15 of the intervention

50 Correction of the cutaneous manifestations of essential fatty acid deficiency in man by application of sunflower-seed oil to the skin. Prottey C. et al J Invest Dermatol 1975;64: Results Deficient patients had higher levels of linoleic acid in the epidermis of the sunflower seed oil arm No change in the olive oil arm Resolution of scaly lesions Epidermal changes not seen in the control group

51 Human essential fatty acid deficiency. Treatment by topical application of linoleic acid. Skolnik P et al. Arch Dermatol. 1977;113: y.o. M with short bowel syndrome from severe IBD Receiving fat-free PN Developed EFAD 150 mg linoleic acid rubbed into R thigh once/day x 3 weeks Changed to safflower oil after 3 weeks

52 Human essential fatty acid deficiency. Treatment by topical application of linoleic acid. Skolnik P et al. Arch Dermatol. 1977;113:

53 Cutaneous application of safflower oil in preventing essential fatty acid deficiency in patients on home parenteral nutrition. Miller DG et al. AJCN. 1987;46: Study of 5 HPN patients 4 weeks no IVFE 4-6 weeks of topical safflower oil (3 mg/kg/d to provide 2.3 mg/kg/d of linoleic acid) 5 ml PO safflower oil once/day x 4 weeks

54 Cutaneous application of safflower oil in preventing essential fatty acid deficiency in patients on home parenteral nutrition. Miller DG et al. AJCN. 1987;46:

55 Cutaneous application of safflower oil in preventing essential fatty acid deficiency in patients on home parenteral nutrition. Miller DG et al. AJCN. 1987;46:

56 Failure of topical vegetable oils to prevent essential fatty acid deficiency in a critically ill patient receiving long-term parenteral nutrition. Sacks GS et al. JPEN. 1994;18: Case report of a critically ill trauma patient requiring fat-free PN because of hypertriglyceridemia Developed EFAD Received topical safflower oil per Miller protocol No resolution of EFAD with use of topical oils alone; resolved when IVFE could be resumed

57 What About Novel Lipids? Gramlich L et al. Essential fatty acid deficiency in 2015: the impact of novel intravenous lipid emulsions. JPEN 2015;39:61S-66S

58 Novel Lipid Case Reports 3 obese patients Required PN for various complications related to GI surgery All received PN for >200 days All started on Intralipid, 2 transitioned to ClinOleic, one received ClinOleic, then SMOF Gramlich L et al. Essential fatty acid deficiency in 2015: the impact of novel intravenous lipid emulsions. JPEN 2015;39:61S-66S

59 Novel Lipid Case Reports Case 1 Case 2 Case 3 BMI (kg/m 2 ) Pre-PN weight (kg) Post-PN weight (kg) Not reported Energy delivery 75% MREE Hypocaloric feeding x 2 months, then MREE MREE Duration of PN (days) * *71 days, then a 1 month break, then another 115 days Gramlich L et al. Essential fatty acid deficiency in 2015: the impact of novel intravenous lipid emulsions. JPEN 2015;39:61S-66S

60 Case 1 72g Intralipid/d x 1 month (36g LA) 60g ClinOleic/d x 1month (12g LA) Decreased to 72g 3x/wk (6.2g LA) x 137d 81.6g ClinOleic x 1 day then 38.4g/d (7.7g LA) x 16 days

61 Case g Intralipid (28.8g LA)/day x 19d 48g Intralipid (24g LA)/day x 23 days No lipid x 14 d 8g Intralipid (4g LA) x 18d 50.4g ClinOleic (10g LA)/day x unspecified time Change to SMOF after for elevated LFTs

62 Case 3 Started with ClinOleic 62.4g (12.5g LA)/day One month off for attempt at oral diet Resumed with ClinOleic 43.2g (8.6g LA/day) for unclear timeframe Changed to Intralipid 50.4g (25g LA)/day x 9 days Changed to SMOF 50.4g (15g LA)/day

63 Novel Lipid Case Reports Case 1 Case 2 Case 3 PN cycled? when able when able when able Average LA delivery EFAD? 11.4 g/day 4.7% total kcals Low LA Normal AA Normal mead acid T:T normal 13 g/day 7% total kcals Normal LA Normal AA Mildly elevated mead acid T:T normal 7.54 g/day 3.7% total kcals Low LA Normal AA Mildly elevated mead acid T:T normal Gramlich L et al. Essential fatty acid deficiency in 2015: the impact of novel intravenous lipid emulsions. JPEN 2015;39:61S-66S

64 Novel Lipid Case Reports Gramlich L et al. Essential fatty acid deficiency in 2015: the impact of novel intravenous lipid emulsions. JPEN 2015;39:61S-66S

Considerations These were obese patients Two lost weight (the 3 rd might have as well) mobilized fat depot If PN was cycled, also promotes fat mobilization Your

65 Considerations These were obese patients Two lost weight (the 3 rd might have as well) mobilized fat depot If PN was cycled, also promotes fat mobilization Your own fat is a source of essential fats! Mascioli EA et al. Effect of total parenteral nutrition with cycling on essential fatty acid deficiency. JPEN 1979;3:

66 Overview Role of essential fats in the body Risk factors for EFAD Drug shortages and EFAD Clinical manifestations & evaluation process Treatment Case study Conclusion

67 IVFE Allergy Case 79 y.o. F with multiple GI surgeries Diverticulitis s/p sigmoid colectomy Colostomy, ileostomy Multiple SBOs, small bowel volvulus Multiple small bowel resections Presented with a high-output ECF

68 IVFE Allergy Case Plan for PN and bowel rest If fistula didn t close spontaneously, then OR Pt was on PN in the past, had h/o anaphylaxis with IVFE Fat-free PN was started

69 IVFE Allergy Case Ideally, would have checked a fatty acid panel prior to starting PN After one month of PN found: Low linoleic acid Low alpha-linolenic acid Triene:tetraene ratio of Lab uses the more sensitive measure, so EFAD is > 0.02 in this case Pt discharged home on PN, returned 11 months later

70 IVFE Allergy Case Pt was seen by a home infusion provider Recommended to take po: 1 tbsp canola oil + 1 tbsp fish oil daily Pt stopped fish oil many months prior to readmission because she was worried about the mercury content She increased to 2 tbsp canola oil daily

71 IVFE Allergy Case Repeat fatty acid panel done 1 month fat free PN 11 months fat free PN Normal range Linoleic acid nmol/ml Alpha-linolenic acid nmol/ml Mead acid nmol/ml Arachidonic acid nmol/ml Triene:tetraene ratio * *EFAD diagnosis should be made at >

72 IVFE Allergy Case Pt went to the OR and had the fistula taken down Diet advanced and pt went home on an unrestricted oral diet!

73 IVFE Allergy Case What should we have done differently? Pushed for an allergy consult Counseled pt on appropriate fats to take po Sunflower, soybean, or safflower would have been better choices Counseled pt to try topical oils At least her PN was cycled!

74 Overview Role of essential fats in the body Risk factors for essential fatty acid deficiency Drug shortages and EFAD Clinical manifestations & evaluation process Treatment Case study Conclusion

Conclusion Identify high-risk patients Look for signs/symptoms of EFAD Evaluate biochemical measures Prevent EFAD when you can Employ treatment options Appropriate IVFE dosing, when

75 Conclusion Identify high-risk patients Look for signs/symptoms of EFAD Evaluate biochemical measures Prevent EFAD when you can Employ treatment options Appropriate IVFE dosing, when there isn t a shortage High intake of essential fats for patients taking an oral diet Cycle the PN Trial of topical oils rich in essential fats Stay tuned for more info on novel lipids

76 POP QUIZ!!!!!!!

77 Test Your Knowledge #1 True or false? The only patients at risk for EFAD are those with malabsorptive disorders or on long-term PN.

78 Test Your Knowledge #1 FALSE! Answer Patients with carnitine deficiency and limited fat intake for many reasons are at risk for EFAD.

79 Test Your Knowledge #2 True or false? EFAD has a very distinctive rash that looks like no other deficiency state.

80 Test Your Knowledge #2 FALSE Answer The dry scaly rash may also indicate zinc deficiency.

81 Test Your Knowledge #3 True or false? Cycling PN may help prevent EFAD.

82 Test Your Knowledge #3 TRUE Answer Cycling promotes mobilization of the body s own linoleic acid stores.

83 References Hise M, Brown JC. Lipids. In: CM Mueller, DS Kovacevich, SA McClave, SJ Miller, DB Schwartz (eds.). The A.S.P.E.N. Adult Nutrition Support Core Curriculum. 2 nd ed. American Society for Parenteral and Enteral Nutrition. Silver Spring, MD. 2012:63-82 Calder PC. Functional roles of fatty acids and their effects on human health. JPEN. 2015;39:18S-39S. Hamilton C, Austin T, Seidner DL. Essential fatty acid deficiency in human adults during parenteral nutrition. Nutr Clin Pract. 2006;21: Siguel EN, Lerman RG. Prevalence of essential fatty acid deficiency in patients with chronic gastrointestinal disorders. Metabolism. 1996;45: Jeppesen PB, Christensen MS, Hoy C-E, Mortensen PB. Essential fatty acid deficiency in patients with severe fat malabsorption. Am J Clin Nutr. 1997;65: Mogensen KM, Pfister DP. Carnitine supplementation: an update. Support Line. 2013;35:3-9. Richardson TJ, Sgoutas D. Essential fatty acid deficiency in four adult patients during total parenteral nutrition. Am J Clin Nutr. 1975;28: Barr LH, Dunn GD, Brennan MF. Essential fatty acid deficiency during total parenteral nutrition. Ann Surg. 1981;193: Piper CM, Carroll PB, Dunn FL. Diet-induced essential fatty acid deficiency in ambulatory patient with type I diabetes mellitus. Diabetes Care. 1986;9: Vanek VW, Allen P, Harvey-Banchik LP, Bistrian B, Collier S, Driscoll DF, Gura K, Houston DR, Miles J, Mirtallo J, Mogensen KM, Seidner D. Parenteral nutrition intravenous fat emulsion product shortage considerations. Nutr Clin Pract. 2013;28: Fleming CR, Smith LM, Hodges RE. Essential fatty acid deficiency in adults receiving parenteral nutrition. Am J Clin Nutr. 1976;29:

84 References O Neill JA, Caldwell MD, Meng HC. Essential fatty acid deficiency in surgical patients. Ann Surg. 1977;185: Duerksen D, McCurdy K. Essential fatty acid deficiency in a severely malnourished patient receiving parenteral nutrition. Digest Dis Sci. 2005;50: Prottey C, Hartop PJ, Press M. Correction of the cutaneous manifestations of essential fatty acid deficiency in man by application of sunflower-seed oil to the skin. J Invest Dermatol. 1975;64: Skolnik P, Eaglstein WH, Ziboh VA. Human essential fatty acid deficiency. Treatment by topical application of linoleic acid. Arch Dermatol. 1977;113: Miller DG, Williams SK, Palombo JD, Griffin RE, Bistrian BR, Blackburn GL. Cutaneous application of safflower oil in preventing essential fatty acid deficiency in patients on home parenteral nutrition. Am J Clin Nutr. 1987;46: Sacks GS, Brown RO, Collier P, Kudsk KA. Failure of topical vegetable oils to prevent essential fatty acid deficiency in a critically ill patient receiving long-term parenteral nutrition. JPEN J Parenter Enteral Nutr. 1994;18: Marccason W. Can cutaneous application of vegetable oil prevent an essential fatty acid deficiency? J Am Diet Assoc. 2007;107:1262. Gramlich L et al. Essential fatty acid deficiency in 2015: the impact of novel intravenous lipid emulsions. JPEN J Parenter Enteral Nutr. 2015;39:61S-66S Mascioli EA, Smith MF, Trerice MS, Meng HC, Blackburn GL. Effect of total parenteral nutrition with cycling on essential fatty acid deficiency. JPEN J Parenter Enteral Nutr. 1979;3:

85 Thank you!

Drug Shortages with Parenteral Nutrition

Drug Shortages with Parenteral Nutrition Carol J Rollins, MS, RD, PharmD, BCNSP Coordinator, Nutrition Support Team The University of Arizona Medical Center www.nutritioncare.org Conflict of Interest None