Essential Fatty Acid Deficiency Phara Jourdan Rosabelle Campos

Essential Fatty Acid Deficiency Phara Jourdan Rosabelle Campos 2005

Essential Fatty Acids The Essential Fats are a group of fatty acids that are essential to human health. • • Omega-3 ( 3) – Linolenic acid Omega-6 ( 6) – Linoleic acid

Structure of EFAs LINOLEIC ACIDS (Omega 6) • – Eighteen-carbon essential fatty acids that contain two double bonds. 18: 2 (9, 12) LINOLENIC ACIDS (Omega 3) Eighteen-carbon essential fatty acids that contain three double bonds 18: 3 (9, 12, 15)

Function of EFAs • Formation of healthy cell membranes • Proper development and functioning of the brain and nervous system • Production of hormone-like substances called Eicosanoids –Thromboxanes –Leukotrienes –Prostaglandins Responsible for regulating blood pressure, blood viscosity, vasoconstriction, immune and inflammatory responses.

Omega-3 s • Sources: Walnuts Wheat germ oil Flaxeed oil/canola oil Fish liver oils/Fish eggs Human Milk Organ meats Seafood/Fatty fish - albacore tuna - mackerel - salmon -sardines

Benefits of Omega-3 s • Lower PG 2 s • Anti-inflammatory • Lower triglyceride and cholesterol levels • Cancer prevention • Renal maintenance • Increase insulin sensitivity • Enhance thermogenesis and lipid metabolism • Benefits vision and brain function • Decrease Skin inflammation • Inhibit platelet adhesion

Reports of -3 Deficiency • Holman and colleagues reported a case of peripheral neuropathy and blurred vision in a child receiving total parenteral nutrition devoid of omega-3 fatty acids for 5 months. 1 -Holman et al. AM J Clin Nutr 35: 617, 1982 • Bjerve and his coworkers reported linolenic acid deficiency in nine patients fed by gastric tube for 2. 5 to 12 years, who had received only 0. 025% to 0. 09% of their total kilocalories as omega-3 fatty acids. -Bjerve et al. Am J Clin Nutr 45: 66, 1987.

Omega-6 s Sources: Corn oil Peanut oil Cottonseed oil Soybean oil Many plant oils Platelet aggregation, cardiovascular diseases, and inflammation

Benefits of Omega-6 s Specifically, omega-6 fatty acids with a high GLA content may help to: • Reduce inflammation of rheumatoid arthritis • Relieve the discomforts of PMS, endometriosis, and fibrocystic breasts. • Reduce the symptoms of eczema and psoriasis. • Clear up acne and rosacea. • Prevent and improve diabetic neuropathy. • Excessive amounts of omega-6 (PUFA) and a very high omega 6/omega-3 ratio has been shown to promote the pathogenesis of many diseases: -cardiovascular disease -cancer -Inflammatory and autoimmune diseases

Essential Fatty Acid Deficiency Side Effects • • • hemorrhagic dermatitis skin atrophy scaly dermatitis dry skin weakness impaired vision tingling sensations mood swings edema • • high blood pressure high triglycerides hemorrhagic folliculitis hemotologic disturbances (ex: sticky platelets) • immune and mental deficiencies • impaired growth

Dermatitis, Atopic in an Infant and on a Young Girl's Face

Differing characteristics -3 and -6 Essential Fatty Acid Deficiencies Omega-3 ( -Linolenic Acid) Omega-6 (Linoleic Acid) Clinical Features Normal skin, growth, reproduction Reduced learning Abnormal electroretinogram Impaired vision Polydipsia Growth retardation Skin lesions Reproductive failure Fatty liver Polydipsia Biochemical markers Decreased 18: 3 -3 and 22: 6 -3 Increased 22: 4 -6 and 22: 5 7 Increased 20: 3 -9(only if -6 also low) Decreased 18: 2 -6 and 20: 4 -6 Increased 20: 3 -9 (only if -3 also low) Guthrie H, Picciano, Mary. Human Nutrition. Lipids p 128 1995

Who are at risk for deficiency? • • Acrodermatitis Enteropathica Long-term TPN patients without adequate lipid • Hepatorenal Syndrome Cystic Fibrosis • Sjogren-Larsson Syndrome Low Birth Weight Infants • Multisystem neuronal degradation Premature infants • Crohn’s disease Severely malnourished patients • Cirrhosis and alcoholism Patients on Long-term MCT • Reye’s Syndrome as fat source • Short bowel syndrome Patients with fat malabsorption

Triene: Tetraene Ratio • T/T ratio is the marker used to diagnose essential fatty acid deficiency. Characterized by: • A decrease of Arachidonic (20: 4 6)acid • An increase of Mead’s acid (20: 3 9). (This acid is produced in excess during EFAD. ) • Triene: Tetraene ratio of >0. 4 is considered EFAD • Some studies suggest a lower threshold of 0. 2 • EFAD development: can be as early as 2 to 4 weeks on TPN without lipids

Effect of TPN on EFAD • Adipose tissue of free-living healthy adults contain 10% of total FA as linoleic acid. • During fat restriction or malabsorption plus energy deficiency, no symptoms appear since linoleic acid and arachidonic acid are slowly released. • During PN without lipids with dextrose, insulin concentrations are high which suppresses adipose tissue mobilization resulting in EFAD within 2 to 4 wks. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients) (2002) Food and Nutrition Board (FNB), Institute of Medicine (IOM)

Topical/PO Application as Treatment for EFAD Review of Literature

Hansen et al. Study done in 1963 • Involved infants fed one of five proprietary milk formulas that were adequate in all other nutrients but contained varying amounts of linoleic acid. • The amounts of linoleic acid varied from 7. 3% down to less than 0. 1% of total kilocalorie needs. Results • A high proportion of the infants who were fed the formula lowest in linoleic acid for 3 months developed dry, thick, flaking skin and suffered from retarded growth. • These clinical problems disappeared when larger amounts of linoleic acid were provided. Pediatrics, 1963

“Cutaneous application of safflower oil in preventing essential fatty acid deficiency in patients on home parenteral nutrition. ” Miller et al. • Investigated the use of cutaneously applied safflower oil to prevent EFAD. • 5 subjects on HPN supplemented with IV fat emulsions underwent a 3 -phase study: 1) no IV fat emulsions for 4 wks 2) cutaneous safflower oil for 4 -6 weeks 3) oral safflower oil for 4 weeks • Fatty acid profiles were obtained during each phase AM J Clin Nutr 1987

Miller et al. (cont) Results 1) No IV fat emulsions for 4 wks Significant decreases in linoleic and arachidonic acid T: T ratio rose from a baseline value of 0. 1 to 0. 5 2) Cutaneous safflower oil for 46 wks Significant increases in linoleic and arachidonic acid occurred. T: T ratio returned to 0. 2 by end of phase 2 3) Oral safflower oil for 4 wk Only 1 of 5 subjects competed the oral phase 3. Conclusion: • Cutaneous safflower oil may improve plasma fatty acid profiles but adequacy of tissue stores remains unanswered. • Liver function tests need to be monitored if this treatment modality is utilized.

“Human essential fatty acid deficiency: treatment by topical application of linoleic acid. ” Skolnik et al. • EFAD developed in a 19 yom who was being maintained on a long-term regimen of fat-free intravenous hyperalimentation fluids. • The EFAD was reversed after 21 days by daily, topical application of linoleic acid to the patient’s skin. • Clinical improvement of EFAD noted with normalizing T/T ratio. • The cutaneous manifestations(scalp dermatitis, alopecia, and depigmentationof hair) were reversed with continued, topical application of safflower oil (which contains 60 -70% linoleic acid) Arch Dermatol. 1977

“Correction of essential fatty acid deficiency in newborn infants by cutaneous application of sunflower-seed oil. ” Friedman et al. • Two newborn infants receiving long-term, fat-free PN developed EFAD. • A Trienoic/Tetraenoic ratio of more than 0. 4 was noted. • Pts received 1400 mg/kg/24 hr of sunflower oil (linoleic 63% linolenic 0. 4%) • Responded to topical therapy 1 -5 days • EFAD rapidly reversed with cutaneous application of sunflowerseed oil Pediatrics 1976

Essential fatty acid deficiency in four adult patients during total parenteral nutrition • • • Richardson, TJ, et al. Four undernourished adults received fat-free TPN for 6 - 8 wks. EFAD (triene: tetraene ratio >. 4) appeared within 3 wks. Earlier deficiency in younger/more undernourished subjects than older/better-nourished Hepatomegaly and increased serum liver enzymes were present in the more severely deficient subjects Oral supplementation with oral linoleic acid as saflower oil reversed EFAD and the elevated serum liver enzymes. NOT A TOPICAL STUDY! Am J Clin Nutr, 1975

Topical Application Ineffective in Treatment of EFAD Review of Literature

“Transcutaneous application of oil and prevention of essential fatty acid deficiency in preterm infants” • Lee, EJ et al. used safflower oil or oil esters (1 g linoleic acid/kg/day) on PN fed (no lipids) preterm infants (n=6). • Not given IV lipid d/t association with hypoxia, chronic lung disease and concern for interference with bilirubin binding • All developed EFAD, fatty acid profiles were similar between control and treatment groups. • EFAD reversed upon IV lipid supplementation Arch Dis Child, 1993

“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. 40 yom injured in MVA on fat-free PN b/c of presence of severe hypertriglyceridemia. developed EFAD, daily topical vegetable oil application • Topical application of linoleic acid-rich oil for three weeks showed no improvement. • Only after IV fat did the pt’s clinical and biochemical signs improve. J Parenter Enteral Nutr, 1994

Plasma and erythrocyte essential fatty acids during total parenteral nutrition in infants: effects of a cutaneous supply • Bougle D, et al. 16 infants on fat free TPN. 10 rubbed 3 x daily x 20 days using oenethera oil (80% EFA) for total of 1900 mg/kg/day. 6 untreated. Compared to control infants. • Day 1 found nonessential FA increased in both groups while n-6 and n-3 FA were decreased in plasma. In RBC phospholipids, oleic acid (16: 0) was increased while n-6 FA were decreased. • Day 20 EFAD worsened with higher than normal triene: tetraene ratio in plasma. In RBC phospholipid, EFA were abnormal while n-9 (nonessential) became significantly increased. • No difference between TPN groups was observed at any time. Showed that cutaneous application of large amounts of EFA-rich oil is unable to prevent/cure TPN induced EFAD. J Parenter Enteral Nutr, 1986

Recommendations: Infants & Children • The American Academy of Pediatrics recommends that infant milk formula should provide at least 2. 7% of total kilocalories in the form of linoleic acid. • Of note, human milk provides 3. 5% to as high as 12% of total kilocalories in the form of linoleic acid depending on the fat composition of the maternal diet. AI for Infants and Children 0 -6 mos 0. 5 g/day of n-3 PUFA 7 -12 mos 0. 5 g/day of n-3 PUFA 1 -3 yrs 0. 7 g/day of -linolenic acid 4 -8 yrs 0. 9 g/day of -linolenic acid Boys 9 -13 yrs 1. 2 g/day of -linolenic acid 14 -18 yrs 1. 6 g/day o -linolenic acid Girls 9 -13 yrs 1. 0 g/day of -linolenic acid 14 -18 yrs 1. 1 g/day of -linolenic acid Food and Nutrition Board, Institute of Medicine (FNBIOM, 2001)

Recommendations: Adults • Requirements for EFAs are 1 to 2% of dietary calories for adults. n Recommended 0. 2% to 1% of total calories should be provided by omega-3 fatty acids. AI for Adults Men 19 - >70 yrs 1. 6 g/day of a-linolenic acid 17 g/day of linoleic acid Women 19 - >70 yrs 1. 1 g/day of a-linolenic acid 12 g/day of linoleic acid Food and Nutrition Board, Institute of Medicine (FNBIOM, 2001)

Conclusion • Important to supplement those at high risk of EFAD with supplementation • Parenterally fed patients become deficient in essential fatty acids unless lipids are administered. • In some cases, cutaneous application of linoleic acid (safflower/sunflower) oil may be beneficial although the literature is mixed.

References • • • 6. 7. 8. Holman RT and others: A case of human linoleic acid deficiency involving neurological abnormalities, AM J Clin Nutr 35: 617, 1982 Bjerve Ks, et al: Alpha-linolenic acid deficiency in patients on long term gastric tube feedings: estimation of linolenic acid and long chain unsaturated n-3 fatty acid requirement in men, Am J Clin Nutr 45: 66, 1987. Hansen AE and others: Role of linoleic acid in infant nutrtion: clinical and chemical study of 428 infants fed on milk mixtures varying in kind amount of fat, Pediatrics 31: 171, 1963 Guthrie H, Picciano, M. Human Nutrition. Mosby-Year Book, Inc. 1995 p 128 Salem N et al. Fatty acids and Lipids from cell biology to human diseases. 31(suppl): S 1 -S 326, 1996 Neuringer M, et al: N-3 fatty acids in the brain and retina: evidence of their essentiality, Nutr Rev 44: 285, 1986 Lloyd-Still, John D. MD Essential fatty acid deficiency and nutritional supplementation in cystic fibrosis. Journal of Pediatrics. 141(2): 157 -159, August 2002. Patients with cystic fibrosis have essential fatty acid deficiency. Journal of Pediatrics. 139(5): 2 A, November 2001.

References 9. 10. 11. 12. 13. 14. 15. Phillips, Sharon K. Pediatric Parenteral Nutrition: Differences in Practice From Adult Care. Journal of Infusion Nursing V 27(3)166 -170 May/June 2004 Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients) (2002) Food and Nutrition Board (FNB), Institute of Medicine (IOM) Lee, EJ, et al: Transcutanneous application of oil and prevention of Essential Fatty Acid Deficiency in preterm infants. Archives of Disease in Childhood. 68(1 spec No): 27 -8, January 1993. Sacks, GS, et al: Failure of topical vegetable oils to prevent Essential Fatty Acid Deficiency in critically ill patient receiving long term parenteral nutrition. Journal of Parenteral and Enteral Nutrition. 18(3): 274 -7, May-June 1994. Bougle D, et al: Plasma and erythrocyte essential fatty acids during total parenteral nutrition in infants: effects of a cutaneous supply. Journal of Parenteral and Enteral Nutrition. 10(2): 216 -9, March-April 1986. Simopoulos AP. Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr. 1991 Sep; 54(3): 438 -63. Richardson TJ, et al: Essential fatty acid deficiency in four adult patients during total parenteral nutrition. American Journal of Clinical Nutrition. 28(3): 258 -263, March 1975.