EPA (Eicosapentaenoic Acid) Deficiency

What Is EPA?

[dropcap]E[/dropcap]PA (eicosapentaenoic acid) is an essential omega-3 fatty acid that is crucial for fetal brain and retina development and the child’s subsequent neurodevelopment among very many other activities in people of all ages.

Omega-3 fatty acids  are polyunsaturated long chain fatty acids which must be obtained from animal foods since they do not occur in plants.

In all ages, EPA is essential for normal brain function.

Q: Why is EPA essential to the way the brain works?

A: EPA helps nerve cells in the brain to communicate with each other.

In pregnancy, EPA may also play a role in determining the length of gestation and in preventing perinatal depression in the mother.¹ and is essential for normal growth in children.

EPA is important building material for the eicosanoids, a large group of highly bioactive hormone-like substances including prostaglandins, leukotrienes, and thromboxanes that are involved in blood clotting, inflammation, and vasoconstriction. Its many important functions are described below.

What Is EPA Deficiency?

• EPA deficiency in celiac disease results when the level within cells is too low to meet metabolic needs of the body for this fatty acid.
• Deficiency is characterized by these features:

• Functional disturbances of attention, cognition, behavior, and mood.
• Alterations in skin integrity, blood clotting responses, inflammatory responses, and immune responses.
• Difficulties with appetite or digestion, temperature regulation and sleep.
• EPA deprivation during pregnancy is associated with impaired developmental and behavior scores of the child.

How Prevalent Is EPA Deficiency in Celiac Disease?

EPA deficiency was found to be common in patients with untreated celiac disease.²

What Are The Symptoms Of EPA Deficiency?

• Aggression.
• Apathy.
• Appetite – poor.
• Blood clotting is too rapid.
• Cognitive disorders including dyslexia and dyspraxia.
• Elevated triglycerides in blood.
• Excessive thirst.
• Eye disorders including dry eye syndrome and macular degeneration.
• Frequent urination.
• Mental disorders including ADHD, depression, bipolar disorder, the schizophrenia spectrum, autistic spectrum disorders.
• Sleep disorders.
• Skin disorders including dry rough skin, eczema, acne, worsening of psoriasis.
• Vascular disorders including hypertension and atherosclerosis.
• In children, tantrums may develop.
• In females, dysmenorrhea and PMS occur.

How Does The Body Get EPA?

• EPA should be obtained in the diet but can be synthesized in the body from alpha-linolenic acid (ALA), a plant source, provided there is adequate ALA available.³
• However, alpha-linolenic acid is not a reliable means of obtaining EPA.⁴
• Additionally, selenium deficiency can interfere with the conversion of alpha-linolenic acid into EPA when needed.

What Does EPA Do In The Body?

1. Required for producing energy in the body.
2. Balances mood.
3. Needed for skin, nail and hair health.
4. Needed for nerve transmission. EPA opposes arachidonic acid in acting as second messenger in chemical neurotransmitter systems as well as contributing to numerous other aspects of cell signaling.
5. Reduces inflammation in response to injury or infection by interfering with the inflammatory effect of opposing eicosanoids derived from arachidonic acid (an opposing omega-6 fatty acid).
6. Limits late stage clotting.
7. Counters vasoconstriction (narrowing of blood vessels) caused by opposing omega-6 fatty acids.
8. Exerts a specific preventive effect against hypertension by enhancing endothelial nitric oxide synthesis, which constricts blood vessels, and suppressing the production of transforming growth factor-B. It inhibits the formation of TXA2, a vasoconstrictor and platelet aggegator, and enhances that of PGI3 , a vasodilator and platelet anti-aggregator.⁵
9. Exerts a preventive effect against atherosclerosis, cardiovascular heart disease and stroke. EPA lowers triglycerides by inhibiting VLDL (very low density lipoprotein), and apoprotein B-100 synthesis and by decreasing abnormal fat in the blood after meals.³
10. Significantly decreases serum triglycerides, which underlie bad cholesterol (LDL).⁶
11. Increases calcium levels in the body, preventing bone loss.

How Does EPA Deficiency Develop In Celiac Disease and/or Gluten Sensitivity?

• EPA deficiency results from fat malabsorption in celiac disease, and
• Lack of necessary vitamin and mineral co-factors needed to use EPA, including zinc, magnesium, manganese, and vitamin B3, vitamin B6 and vitamin C.

Does EPA Deficiency Respond To Gluten Free Diet?

Yes. Celiac disease-related EPA deficiency responds to a nutritious gluten free diet containing adequate EPA. Direct intake of preformed EPA supplement is likely to be most effective, as alpha-linoleic acid to EPA conversion may be limited.

6 Steps To Correct EPA Deficiency:

• [dropcap]1[/dropcap]Meet, or Exceed the AI(Adequate Intake) Requirement for EPA in milligrams (mg) per day:

[box type=”success” ]Requirements are not established to prevent deficiency.[/box]

• [dropcap]2[/dropcap]Diet – Include Food Sources Richest in EPA:

[box type=”shadow” ]Plant sources are not a source of EPA.

Highest Animal Sources

Deep Ocean Fish Oil: Menhaden fish oil. Cod liver oil. Salmon oil. Herring oil.

High Animal Sources Come from Fish:

• Sardines in oil.
• Pacific herring.
• Mackerel.
• Chinook salmon.
• Sablefish.
• Atlantic herring.
• Atlantic sturgeon.
• Then halibut,sockeye salmon, anchovy, and mullet.

Lesser amounts:

• High omega-3 eggs.
• Common periwinkle.
• Conch.
• Pacific oyster.³[/box]

• [dropcap]3[/dropcap] Diet – Avoid, Limit, or Eat Separately These Foods That Deplete or Interfere With Absorption:

[box type=”shadow” ]

• Deep fried foods fried in trans-fats.
• Meat.
• Milk products.
• Alcoholic drinks.

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• [dropcap]4[/dropcap]Monitor Medications That Deplete, Interfere With Absorption, Or Involve Other Interactions:

[box type=”shadow” ]

Here are common medications that interact with EPA. Ask your doctor or pharmacist about this possible adverse effect if you are taking any of the drugs listed below. Do not stop prescribed medications without supervision.

This is not a complete listing.

CHOLESTEROL LOWERING DRUGS

• Fat binding medications like Colestid, Questran interfere with absorption of EPA.

BILE SEQUESTRANTS

• Cholestyramine, colestipol interfere with absorption of EPA.

BLOOD-THINNING MEDICATIONS — Omega-3 fatty acids may increase the blood-thinning effects of warfarin (Coumadin), aspirin, or other blood-thinning medications, leading to the risk of increased bleeding. They should only be taken together under your doctor’s supervision.⁷. Includes Non-steroidal antiinflammatory drugs (NSAIDS) like Ibuprofen.[/box]

• [dropcap]5[/dropcap]Manage Nutritional Supplements to Obtain EPA:

[box type=”shadow” ]

• Fish oil soft gel capsules, tablets and liquid supplements.
• Flax oil capsules and liquid supplements supply alpha-linolenic acid, which is a parent omega-3 fatty acid that the body can convert to EPA… but this unreliable conversion is at a low level AND requires adequate vitamin co-factors to be available.

Caution: At high doses eicosapentaenoic acid supplements can increase the risk of bleeding and hemorrhagic stroke because of its anti-clotting effect.   

Do not use EPA supplements without the advice of your physician if:

• You are pregnant or breast-feeding.
• You have high blood triglyceride levels.
• You have prostate cancer or are at high risk for prostate cancer (e.g., father or brother with prostate cancer).⁸[/box]

• [dropcap]6[/dropcap]Other Supplements That Deplete or Interfere With Absorption:

[box type=”shadow” ]

• Arachidonic acid supplements.

Check with your pharmacist.[/box]

What Do Medical Research Studies Tell About EPA Deficiency In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials.” This study investigating evidence and seeking to provide an updated meta-analysis of all double-blind, placebo-controlled, randomized controlled trials (28) examining the effect of omega-3 fatty acid supplementation in which depressive symptoms were a reported outcome found that EPA may be more efficacious than DHA in treating depression. The study also aimed to specifically test the differential effectiveness of EPA versus DHA through meta-regression and subgroup analyses.

Meta-regression studies showed a significant effect of higher levels of baseline depression and lower supplement DHA EPA ratio on therapeutic efficacy. Subgroup analyses showed significant effects for: (1) diagnostic category (bipolar disorder and major depression showing significant improvement with omega3 supplementation versus mild-to-moderate depression, chronic fatigue and non-clinical populations not showing significant improvement); (2) therapeutic as opposed to preventive intervention; (3) adjunctive treatment as opposed to monotherapy; and (4) supplement type. Symptoms of depression were not significantly reduced in 3 studies using pure DHA or in 4 studies using supplements containing greater than 50% DHA.

In contrast, symptoms of depression were significantly reduced in 13 studies using supplements containing greater than 50% EPA and in 8 studies using pure ethyl-EPA . However, further meta-regression studies showed significant inverse associations between efficacy and study methodological quality, study sample size, and duration, thus limiting the confidence of these findings.⁹

Sources:

1. Coletta JM, Bell SJ, and Roman AS. Omega-3 Fatty Acids and Pregnancy. Rev Obstet Gynecol. 2010 Fall; 3(4): 163–171 [↩]
2. Krums LM, Pafenov AI, Ekisenina NI. Disorders in lipid metabolism in patients with chronic diseases of the small intestine. Klinicheskaia Meditsina. Nov 1990; 68(11):54-7. [↩]
3. Kathleen Mahan and Sylvia Escott-Stump, ed. Krause’s Food, Nutrition & Diet Therapy, 10th Edition. Philadelphia, PA. USA: W.B. Saunders Company, 2000. [↩] [↩] [↩]
4. Richardson AJ. The importance of omega-3 fatty acids for behavior, cognition, and mood. Scandinavian Journal of Nutrition. 2003;47(2):92-8 [↩]
5. Das N. Long chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth-B to prevent human essential hypertension. European Journal of Clinical Nutrition. 2004; 58:195-203. [↩]
6. Egert S, Kannenberg F, Somoza V, et al. Dietary alpha-linolenic acid, EPA, and DHA have differential effects on LDL fatty acid composition but similar effects on serum lipid profiles in normolipidemic humans. J Nutr. 2009;139:861–868. doi: 10.3945/jn.108.103861 [↩]
7. Possible Interactions with: Alpha-Linolenic Acid (ALA) | University of Maryland Medical Center http://umm.edu/health/medical/altmed/supplement-interaction/possible-interactions-with-alphalinolenic-acid-ala#ixzz3HT7cshoK  [↩]
8. http://www.medicinenet.com/alpha-linolenic_acid-page2/supplements-vitamins.htmaccessed 12/9/12 [↩]
9. Martins JG. EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr. 2009 Oct;28(5):525-42. [↩]