Transcript Essential Fatty Acid Deficiency

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.
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Omega-3 (3) – Linolenic acid
Omega-6 (6) – Linoleic acid
Structure of EFAs
LINOLEIC ACIDS (Omega 6)
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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-3s
• 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-3s
• Lower PG2s
• 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
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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
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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-6s
Sources:
Corn oil
Peanut oil
Cottonseed oil
Soybean oil
Many plant oils
Platelet aggregation, cardiovascular
diseases, and inflammation
Benefits of Omega-6s
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
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hemorrhagic dermatitis •
skin atrophy
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scaly dermatitis
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dry skin
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weakness
impaired vision
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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 p128 1995
Who are at risk for deficiency?
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• Acrodermatitis
Enteropathica
Long-term TPN patients
without adequate lipid
• Hepatorenal Syndrome
Cystic Fibrosis
• Sjogren-Larsson
Syndrome
Low Birth Weight Infants
• Multisystem neuronal
Premature infants
degradation
Severely malnourished
• Crohn’s disease
patients
• Cirrhosis and alcoholism
Patients on Long-term
MCT as fat source
• Reye’s Syndrome
Patients with fat
• Short bowel syndrome
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, Fat, 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
4-6 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 1400mg/kg/24hr of sunflower oil (linoleic 63%
linolenic 0.4%)
• Responded to topical therapy 1-5 days
• EFAD rapidly reversed with cutaneous application of
sunflower-seed oil
Pediatrics 1976
Essential fatty acid deficiency in four adult patients
during total parenteral nutrition
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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 (1g 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 3x 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.
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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
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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 and
amount of fat, Pediatrics 31:171, 1963
Guthrie H, Picciano, M. Human Nutrition. Mosby-Year Book, Inc. 1995 p128
Salem N et al. Fatty acids and Lipids from cell biology to human diseases.
31(suppl): S1-S326, 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):2A, November 2001.
References
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Phillips, Sharon K. Pediatric Parenteral Nutrition: Differences in Practice From Adult Care.
Journal of Infusion Nursing V27(3)166-170 May/June 2004
Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, 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):2169, 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.