SOURCES OF ESSENTIAL FATTY ACIDS ! !-3 FAs !

certain vegetable oils, fish, fish oils (mixture of DHA & EPA) ! !-6 FAs ! safflower oil & corn oil ! Longer-chain !3 FAs ! cod liver oil & salmon oil ! Both !-6 and !-3 FAs ! canola oil & soybean oil ! Meat and eggs (smaller amounts) ! Nuts and nut oils

FUNCTIONS

Cell membrane formation Reproduction Transport of metabolites !!i.e. cholesterol Precursors of prostaglandins

SYMPTOMS OF DEFICIENCY AND TOXICITY

Deficiency "!fatigue "!poor memory "!dry skin "!heart problems "!mood swings or depression "!poor circulation Toxicity "!affects antioxidant properties "!mercury poisoning

BIOCHEMICAL BASIS OF SYMPTOMS

EPA "eicosanoids !-6 & !-3 messengers have opposite effects !-6 prostaglandin mediators = pro-arrhythmic !! TXB2 from !-6 FAs activates platelets & causes vasoconstriction ! EPA & DHA messengers = anti-arrhythmic, antiinflammatory, or vasodilators !! TXB3 from !-3 FAs inhibits platelets & causes vasodilation

Name of Study: "-Linolenic acid and long-chain !-3 fatty acids supplementation in three patients with !-3 fatty acid deficiency: effect on lymphocyte function, plasma and red cell lipids, and prostanoid formation Authors: Kristian S Bjerve, Sven Fischer, Finn Wammer, and Torstein Egeland Year: 1989

OBJECTIVES To extend their knowledge of the essentiality of !-3 fatty acids in humans. To figure out the effects of supplementing incremental amounts of "-linolenate followed by incremental amounts of long-chain !-3 fatty acids given to three patients with !-3 fatty acid deficiency.

SUBJECTS
!-3 fatty acid deficiency Five adults age 59-90 years old One 6 year-old child One 7 year-old girl Patients 1, 2, and 3 awake during the day not coming in contact with anything around her or having any spontaneous muscular activity

PATIENT 1 Male born in 1959 (~114 lbs. at start of study) Gastric tube feeding since Feb. 1973 (brain damage) 200g powdered nutrient mixed w/2L whole milk for 4 mo., 100 g w/1L whole milk, 0.75L skimmed milk, 0.25L 120 g glucose/L for 5 mo., 100 g w/1.5L skimmed milk & 0.5L of 120 g glucose/L for 3 mo. Deficiency signs: dermatitis on face & legs, heavily seborrhoeic scalp & partly hemorrhagic folliculitis

PATIENT 2
Female born in 1956 (~112 lbs. at start of study) Brain damage, confined to bed with gastric tube 300 g Collett spesialdiett with 2.4L/day of H2O for 72 months. Deficiency signs: Slight, scaly dermatitis on arms & dorsal side of feet, 73 by 48 mm pressure ulcer on buttocks & edemas in surrounding areas. Ulcer was noncompliant with treatment for 1.5 y

PATIENT 3
Female born in 1946 (~132 lbs. 6 mo. start of study) Diagnosed w/Multiple sclerosis in 1972 2000 kcal/day of a nutrient with 16.2% of calories from 18:2 !-6 & 0.07 % from 18:3 !-3 until 1984 200 g Collett spesialdiett w/2L of whole milk Deficiency signs: scaly & erythematous intertriginous lesions in palms, partly hemorrhagic folliculitis in scalp & severe seborrhea, slight scaly dermatitis on hands & feet

DESIGN OF STUDY Began in March 1986 3 oldest patients lived in same senior home All on same gastric tube feeding commercially available powdered nutrient (Colletts spesialdiett) mixed w/H2O and skimmed milk !!Composed of dried skimmed milk, corn oil, maltodextrin, saccharose, vitamins, and minerals.

NUTRIENT COMPOSITION OF POWDER (100 G)

! 380 kcal

! 1.3 g fat ! 19.0 g protein ! 73 g carbohydrates

0.38 mg vitamin A 5 #g vitamin D 9.9 mg vitamin E 0.83 mg thiamin 1.02 mg riboflavin 1.14 mg vitamin B6 ! 3.19 #g vitamin B12 ! 8.0 mg niacin ! ! ! ! ! !

! ! ! ! ! ! !

! 526 mg inorganic phosphorous ! 18 mmol calcium ! 2.8 mmol magnesium ! 13.7 mmol sodium ! 22.3 mmol potassium ! 15.1 mg iron 5.0 mg pantothenic acid ! 0.53 mg copper ! 2.9 mg zinc 22.0 #g folic acid ! 0.76 mg manganese 116 #g biotin ! 33.3 #g iodine 7.32 mg choline 73.2 mg inositol 90.3 mg p-aminobenzoic acid 33.3 mg vitamin C

SUPPLEMENTS
0.12 mL ethyl "-linolenate for 14 days # to 0.5 mL each day for 14 days. highly purified fish oil (49.4 wt % as long-chain !-3 acids & 5.3 wt. % of !-6 acids) 0.5 mL EPA-oil/day for 2 weeks 2.5 mL/day for the following 2 weeks !!Post-study the subjects received 10 mL soya oil and 5 mL cod liver oil split into doses.

CHEMICAL AND BIOLOGICAL ASSAYS 1

! ! ! ! ! Isolated plasma erythrocyte lipids w/ nondecanoic acid & butylated hydroxytoluene Capillary GLC determined amount of FAs Methanolic Na+ transmethylated & examined phospholipid FAs Chloroform-methanol determined FA content Capillary GLC analyzed FA methylesters with trinonadecanoin

GLC = Gas Liquid Chromatography

CHEMICAL AND BIOLOGICAL ASSAYS 2

! ! 3 men & 6 women aged 23-40 years old volunteered as controls PGI2-M & PGI3-M - examined as their pentaflurobenzylester-methoximetrimethylsilylether derivatives using deuterated PGI2-M TXB2 ! allowed to clot at 37C for 1 hour ! concentrations measured w/ radioimmunoassay & antiserum

CHEMICAL AND BIOLOGICAL ASSAYS 3

! ! ! Bleeding time measured w/Simplate-II Bleeding Time Device Peripheral nerve conductivity measured with Neuromatic 2000C instrument Isopaque-Ficoll gradients extracted mononuclear cells to analyze the lymphocytes stimulating effects on mitogens

RESULTS
Only needed 0.12 mL/day of "-linolenate to: !!reduce hemorrhagic folliculitis in patients 1 & 2 !!induce epidermal growth in the third patient !!Skin changes began to normalize when "linolenate intake was >115 mg/d of total calories !!Skin of patients 2 & 3 healed with 500-550 mg/d !!470 mg/d partly normalized facial dermatitis in patient 1

HOW THEY FOUND THE AI $! Estimated 350-400 mg per day of long-chain !-3 fatty acids will allow adults to maintain a normal amount of !-3 FAs $! For 18:3!-3 acids, they calculated 405-1655 mg/day (average of 990 mg/day & 1% of cals) $! 1.1-1.2% in the 7-year-old girl with !-3 deficiency who received 16.2% of her calories from linoleic acid

!-LINOLENIC ACID AI SUMMARY, AGES 19 YEARS AND OLDER

AI for Men 19-30 years 31-50 years 51-70 years >70 years AI for Women 19-30 years 31-50 years 51-70 years >70 years
$ (From ("Dietary Fats: Total Fat and Fatty," 2005,$p. [Page 471]).

1.6 g/d of "-linolenic acid 1.6 g/d of "-linolenic acid 1.6 g/d of "-linolenic acid 1.6 g/d of "-linolenic acid 1.1 g/d of "-linolenic acid 1.1 g/d of "-linolenic acid 1.1 g/d of "-linolenic acid 1.1 g/d of "-linolenic acid

REFERENCES
Bjerve KS. 1989. n-3 Fatty acid deficiency in man. J Intern Med 1989; 225:171175. Bjerve KS, Fischer S, Wammer F, and Egeland T. "-Linolenic acid and long-chain !-3 fatty acids supplementation in three patients with !-3 fatty acid deficiency: effect on lymphocyte function, plasma and red cell lipids, and prostanoid formation. Am J Clin Nutr 1989; 49: 290-300. Bjerve KS, Mostad IL, Thoresen L. Alpha-linolenic acid deficiency in patients on long-term gastrictube feeding: Estimation of linolenic acid and long-chain unsaturated n-3 fatty acid requirement in man. Am J Clin Nutr 1987a.; 45:6677. Bjerve KS, Thoresen L, Mostad IL, Alme K. Alpha-linolenic acid deficiency in man: Effect of essential fatty acids on fatty acid composition. Adv Prostaglandin Thromboxane Leukot Res 1987b.; 17:862865. Dietary fats: Total fat and fatty acids. (2005). In Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (pp. 422-541). Gropper, S. S., & Smith, J. L. (2013). Lipids. In Advanced nutrition and human metabolism (Sixth ed., pp. 137-182). Yolanda Cossio. ! Kris-Etherton PM, Taylor DS, Yu-Poth S, Huth P, Moriarty K, Fishell V, Hargrove RL, Zhao G, Etherton TD. 2000. Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr 71:179S188S. Omega-3 fatty acids. (2011, May 10). Retrieved October 30, 2013, from University of Maryland Medical Center website: http://umm.edu/health/medical/altmed/supplement/omega3-fattyacids#ixzz2is3feOfn