Food as medicine in essential fatty acids. Linoleic fatty acid, alpha-linolenic fatty acid, eicopentaenoic acid (EPA) and docohexaenoic acid (DHA). Inflammatory lipid mediators. Specialized proresolving mediators. Importance of omega-6/omega-3 ratio. causes of essential fatty acid deficiecny. Treatment and prevention of essential fatty acid deficiency.

1. FOOD AS MEDICINE:
ESSENTIAL FATTY ACID
By
Kevin KF Ng, MD, PhD
Former Associate Professor of Medicine
Division of Clinical Pharmacology
University of Miami, FL. USA
Email: kevinng68@gmail.com
Slide presentations delivered to health-care providers in 2017

2. What is Food and What is Medicine?
▪ Food: a nourishing substance that is taken into the body
to sustain life, provide energy and promote growth.
▪ Medicine: the science or practice of the
diagnosis, treatment and prevention of disease.

3. What is in the Food?
Food
Nutrients
Macronutrients
Carbohydrate
Protein
Fat
Fiber
Micronutrients
Minerals
Vitamins
Phytochemicals
Fatty acids
Water

4. What are Essential Fatty Acids (EFA)
Essential fatty acids (EFA) are fatty acids that humans and other animals
must ingest because the body requires them for good health but cannot
synthesize them

5. Essential fatty acids ALA, EPA, DHA, LA, AA

6. History of Essential Fatty Acids
In 1929 George and Mildred Burr found that if
essential fatty acids were missing in the diet, a
deficiency syndrome ensued and often led to
death.
The Burrs subsequently identified linoleic acid
(omega-6 PUFA) and linolenic acid (omega-3 PUFA)
as essential substances in the diet and coined the
phrase “essential fatty acid”
Essential fatty acids are also known as Vitamin F.

7. Milestones on the discovery of essential fatty acids, eicosanoids
and specialized pro-resolvin mediators
Kevin Ng’s mentor

8. An outline of Fats and Fatty acids

9. Source of polyunsaturated fatty acids
Polyunsaturated fatty acids
Omega-6 fatty acid Omega-3 fatty acid
Plant derived Plant derived Marine derived
linoleic acid (LA) α-linolenic acid(ALA) eicosapentaenoic acid(EPA)
docosahexaenoic acid(DHA)

10. Examples of Fats and Essential fatty acids

11. ANATOMICAL LOCALIZATION OF FATTY
ACIDS IN THE BODY

12. Proportions of various species of fatty acids in rat whole body.
categorized fatty acids
major n-3 PUFA as % of total n-3 PUFA major n-6 PUFA as % of total n-6 PUFA
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4555191/
Ratio:
1:6
LA
AA
ALA
DHA
EPA

13. Descending order of concentration of PUFA in organs of rat
Phospholipid Fatty Acid Organ
Omega-6 LA_Linoleic acid Skin, liver, stomach
Omega-6 AA_Arachidonic acid Liver, kidney, pancreas
Omega-3 ALA_α-linolenic acid Skin, stomach, liver
Omega-3 EPA_eicosapentaenoic acid Pancreas, liver, salivary gland
Omega-3 DHA_docohexaenoic acid Brain, liver, spinal cors
Adapted from Prostaglandins, Leukotrienes, and Essential Fatty Acids, 2015,100, 13–20.

14. Omega-3 phospholipid and cell membrane lipid structure
http://www.alamy.com/stock-photo-omega-3-phospholipid-and-skin-cell-membrane-lipid-layer-structure-81535164.html

15. Omega-3 phospholipid and cell membrane lipid structure
Adapted from alamy.com/stock-photo-omega-3-phospholipid-and-skin-cell-membrane-lipid-layer-structure

16. Cell membrane and phospholipid molecule
Image modified from OpenStax Biology.
Unsaturated fatty acidSaturated fatty acid

17. Functions of Essential Fatty Acids
▪ Structure of healthy cell membranes
▪ Development of brain and nervous system
▪ Support healthy skin and hair
▪ Maintain healthy endothelial function
▪ Precursors of pro-inflammatory mediators
Prostaglandins
Leukotrienes
Thromboxanes
▪ Precursors of pro-resolving mediators
Lipoxins
Resolvins
Protectins
Maresins
Cell membrane

18. Phospholipds: release and metabolism of
linoleic acid and α-linolenic acid
PLA₂
Saturated fatty acid Unsaturated fatty acid

19. Actions of inflammatory mediators produced by
Arachidonic acid
▪ Pain Prostaglandins
▪ Swelling Inflammation caused by lipid mediators Leukotrienes
▪ Redness Thromboxanes
▪ Heat

20. Actions of Specialized Pro-resolving Mediators (SPM)
produced by EPA and DHA
▪ Act as “stop signals” to turn off inflammation
▪ Initiate resolution, repair and regeneration
▪ Facilitate macrophage to clear apoptotic cells
(efferocytosis)
▪ Facilitate macrophage to migrate to peripheral lymph nodes
(efflux)

21. Health benefits of omega-6 fatty acid
▪ Growth and development
▪ Brain and retina function
▪ Skin and hair growth
▪ Maintain bone health
▪ Regulate metabolism
▪ Maintain reproductive system

22. Health benefits of omega-3 fatty acid
http://www.prweb.com/releases/health-benefits-omega-3/natural-omega-3-health/prweb11741699.htm

23. Functional differences between essential fatty acids
Omega-3 fatty acid
▪ Movement of calcium across cell membrane
▪ Relaxation and contraction of muscles
▪ Cell division
▪ Growth
▪ Blood clotting
▪ Lower triglyceride
▪ Fertility
▪ Reduce risks of heart disease, cancer and diabetes
▪ Precursor to pro-resolving mediators
Omega-6 fatty acid
▪ Growth and development
▪ Brain and retina development
▪ Stimulate skin health
▪ Stimulate hair growth
▪ Maintain healthy bone
▪ Regulate metabolism
▪ Lower cholesterol and triglyceride
▪ Maintain healthy reproductive system
▪ Precursor to inflammatory mediators

24. DISORDERS DUE TO
ESSENTIAL ACID DEFICIENCY

25. Disorders due to essential fatty acid deficiency
▪ Dermatitis
▪ Increase water permeability of the skin
▪ Increased susceptibility to infection
▪ Impaired wound healing
https://www.mayomedicallaboratories.com/test-catalog/Clinical+and.../82426

26. Disorders due to essential fatty acid deficiency:
“Disease of civilization”
▪ Hear disease
▪ Hyperlipidemia
▪ Diabetes mellitus
▪ Rheumatoid arthritis
▪ Brain dysfunction
▪ Visual disorder
▪ Skin disease

27. Signs and symptoms due to essential fatty acid deficiency
Omega-3 fatty acid deficiency
▪ Poor memory
▪ Mood disorder
▪ Depression
▪ Poor circulation
▪ Heart problems
▪ Fatigue
▪ Dry scaly skin
▪ Arthritis
Omega-6 fatty acid deficiency
▪ Skin eruption
▪ Slow wound healing
▪ Behavioral problem
▪ Heart problem
▪ Circulation problem
▪ Sterility in man
▪ Miscarriage in pregnant woman

28. LABORATORY TESTS FOR
ESSENTIAL FATTY ACID DEFICIENCY

29. Laboratory tests for essential fatty acid deficiency
▪ Diminished level of linoleic acid (ω-6)
▪ Diminished level of α-linoleic acid (ω-3)
▪ Abnormal red blood cell fatty acid profile
▪ Omega-3 index: (desirable range 8-12%)
▪ Omega-6 to omega-3 ratio: (desirable range 2:1-10:1)
▪ Arachidonic acid to EPA ratio (desirable range: 2:1-71:1)

32. The importance of the ratio of omega-6/omega-3 essential fatty acids
▪ Excessive amounts of omega-6 PUFA and a
▪ very high omega-6/omega-3 ratio (20:1 in Western diet)
Inflammatory disease
Cardiovascular disease
Cancer
Autoimmune disease
Neurodegenerative disease
Obesity

33. The importance of the ratio of omega-6/omega-3 essential fatty acids
▪ Excessive amounts of omega-6 PUFA and a
▪ very high omega-6/omega-3 ratio (20:1 in Western diet)
Inflammatory disease
Cardiovascular disease
Cancer
Autoimmune disease
Neurodegenerative disease
Obesity

34. omega-3 FA: omega-6 FA ratio in USA
http://www.smarternootropics.com/omega-3/ http://www.aqua.stir.ac.uk/nas/blood-spot-test/

35. Omega 6 fatty acid overload

36. Population omega-3 fatty acid in select countries
http://suppversity.blogspot.com/2013/10/sesame-powered-high-omega-6-diet-boosts.html

37. CHD Mortality and Tissue HUFA
http://lipidlab.com/services/

38. https://www.nutraingredients-usa.com/Article/2009/06/26/Omega-3-deficiency-causes-96-000-US-deaths-per-year-say-researchers

39. What is the cause of high concentration of omega-6 fatty acid in US population?
▪ Dietary vegetable oil
▪ Red meat
96% of oils consumed in US include
Soybean oil, cottonseed oi
Corn oil, canola oil

40. http://coachmikeblogs.com/eat-fish-or-take-fish-oil/

41. Increase in adipose tissue LA concentration over time,
buttocks and abdominal subcutaneous only
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC46424

42. ESSENTIAL FATTY ACIDS IN
VEGETABLE OILS AND FOODS

43. Omega-6 and omega-3 content of various
vegetable oils and foods
Adapted from https://chriskresser.com/

44. Composition of omega-3 FA and mercury in fishes
http://www.1vigor.com/article/omega-3-fatty-acids-health-benefits/

45. Fatty acid content:omega-6/omega-3 ratio in Fats & Fatty Acids
(grams per tablespoon)
http://www.gbhealthwatch.com/Science-Omega3-Omega6.php

46. CAN THE PLANT DERIVED
ALPHA-LINOLENIC ACID (ALA) BE
CONVERTED TO EPA & DHA?

47. Metabolic pathways of polyunsaturated fatty acid
by same enzymes
https://www.researchgate.net/publication/25870110
Anti-inflammatory Inflammatory

48. Conversion of ALA to EPA and DHA
With saturated FA meal
EPA
ALA
DHA
With n-6 PUFA meal
EPA
ALA
DHA
6%
3.8%
3%
1.9%
https://www.ncbi.nlm.nih.gov/pubmed/9637947

49. Metabolic pathways of polyunsaturated fatty acid
https://openi.nlm.nih.gov/detailedresult.php?img=PMC4418048_13058_2015_571_Fig1_HTML&req=4

51. Generation of Specialized pro-resolving mediators from EPA & DHA
EPA=eicosapentaenoic acidALA=α-linolenic acid DHA=docosahexaenoic acid

52. Functions of Specialized Pro-resolving Mediators (SPM)
▪ Act as “stop signals” to turn off inflammation
▪ Initiate resolution, repair and regeneration
▪ Facilitate macrophage to clear apoptotic cells
(efferocytosis)
▪ Facilitate macrophage to migrate to peripheral lymph nodes
(efflux)

53. How much essential fatty acids (EPA+DHA) is required for
optimal health?
▪ No adequate intake (AI) or Dietary Reference Intake (DRI) has been
established in the United States yet.
▪ Expert health organizations and health professionals recommend
● 250 mg to 1000 mg EPA+DHA per day or
● 2 servings of salmon 4 oz a day twice weekly

54. CAUSES OF ESSENTIAL FATTY ACID
DEFICIENCY

55. Causes of essential fatty acid deficiency (rare)
▪ Unbalanced Diet : excessive omega-6 fatty acid
deficiency in omega-3 fatty acid
▪ Medical causes
▪ Surgical causes

56. Causes of essential fatty acid deficiency (cont.)
Medical
▪ Inflammatory bowel disease
▪ Cystic fibrosis
▪ Pancreatic insufficiency
▪ Carnitine deficiency
▪ Enteral fat restrition
Surgical
▪ Massive bowel resection
▪ Enterocutaneous fistula
▪ Bariatric surgery
▪ TPN with no emulsion

57. Dietary sources of omega-6 fatty acids
▪ poultry
▪ eggs
▪ nuts
▪ hulled sesame seeds
▪ cereals
▪ durum wheat
▪ whole-grain breads
▪ most vegetable oils
▪ grape seed oil
▪ evening primrose oil
▪ borage oil
▪ blackcurrant seed oil
▪ flax/linseed oil
▪ rapeseed or canola oil
▪ hemp oil
▪ soybean oil
▪ cottonseed oil
▪ sunflower seed oil
▪ corn oil
▪ safflower oil
▪ pumpkin seeds
https://en.wikipedia.org/wiki/Omega-6_fatty_acid

58. Sources of preformed EPA and DHA

59. Prevention and treatment of
essential fatty acid deficiency
Prevention
▪ Provide at least 10% of total calories from fat
▪ Provide at least 2%-4% of calories from
linoleic acid
▪ Assure adequate provision of carnitine in at-
risk patients
▪ Cystic fibrosis patients
▪ Council patients taking an oral diet to increase
intake of foods rich in essential fatty acids.
Treatment
▪ For PN-dependent patients, increase LA
delivery from lipid injectable emulsion
▪ Evaluate for carnitine deficiency and
treat if deficient
▪ For patients taking an oral diet,
encourage vegetable oils, condiments,
nuts and nut butters rich in EFA
▪ Consider lipid injectable emulsion
infusion periodically either while
inpatient or at an outpatient infusion
site.

60. Recommended intakes of seafood/fish and
marine-derived essential fatty acids
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067287/table/Tab2/

61. Dose response of EPA+DHA after clinical events
http://coachmikeblogs.com/eat-fish-or-take-fish-oil/

62. Side effects of essential fatty acids
Common (1% to 10%):
Eructation, dyspepsia, nausea, gastrointestinal disorders (including abdominal
distension, abdominal pain, constipation, diarrhea, flatulence, gastroesophageal
reflux disease, vomiting)
Uncommon (0.1% to 1%): Gastrointestinal hemorrhage, gastroenteritis
Rare (less than 0.1%): Gastrointestinal pain
Very rare (less than 0.01%): Lower gastrointestinal hemorrhage
https://www.drugs.com/sfx/omega-3-polyunsaturated-fatty-acids-side-effects.html

63. Possible drug and omega-3 fatty acid interactions
▪ Increase effect of blood thinning medications
▪ Increase effect of non-steroidal anti-inflammatory drugs
▪ Increase effect of blood sugar lowering medications
▪ Increase effect of cholesterol lowering medications
▪ Reduce side effects of cyclosporine during chemotherapy
▪ Improve symptoms of psoriasis with Etretinate and topical steroids
http://pennstatehershey.adam.com/content.aspx?productId=107&pid=33&gid=000971

64. Conclusions
▪ Essential fatty acids (EFA) are essential because they cannot be synthesized by the
human body and they must be ingested from external sources.
▪ There are only two EFA : ω-6 linoleic acid (LA) and ω-3 α-linolenic acid (ALA). ALA is
converted to ecosapentaenoic acid (EPA) thence to docosahexaenoic acid (DHA)
▪ The functions of EFA include growth and development, regulation of permeability and fluidity
of cell membrane, source of precursors for eicosanoids and specialized pro-resolving
mediators, influence on membrane enzymes, cellular transduction, neurotransmission and
transport activity.
▪ A high ration of ω-6/ω-3 (>4:1) leads to an inflammatory state which underlies
the disease of civilization: heart disease, hyperlipidemia, diabetes mellitus,
auto-immune disease, brain dysfunction, visual disorder and skin disease.
▪ Deficiency of EFA and a high ω-6/ω-3 ratio can be corrected by adjusting the
intake of plant derived linoleic acid and marine derived EPA and DHA

65. ANY QUESTION?
Contact
Kevin KF Ng, MD, PhD
Email: kevinng68@gmail.com