DHA (Docosahexaenoic Acid) Deficiency

What Is DHA?

[dropcap]D[/dropcap]ocosahexaenoic acid (DHA) is an essential omega-3 fatty acid that is abundant in the brain, being crucial in brain structure. As such DHA is a key component of neuronal membranes together with arachidonic acid (a major opposing omega-6 fatty acid), making up 15-20% of the brain’s dry mass.

This polyunsaturated fatty acid is obtained from fish sources of food.

In healthy human volunteers, positron emission tomography (PET) has shown that the normal human brain consumes 4.6 mg/day of DHA.¹

DHA is particularly concentrated in highly active membranes such as nerve synapses (junctions) and photoreceptors in the eye (retina).

Q: How much DHA is in the retina?

A: DHA makes up more than 30% of the retina.²

In other roles, DHA is an  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.

DHA has been shown to increase insulin sensitivity as opposed to the opposite problem of insulin resistance, to improve muscle mass, and protect against non-alcoholic fatty liver disease.³

Egert et al. in a study of people aged 19 to 43 years with normal cholesterol showed that DHA intake significantly increased serum HDL (good) cholesterol. Also, DHA significantly decreased fasting serum triglycerides.⁴

What Is DHA Deficiency In Celiac Disease and/or Gluten Sensitivity?

• Relationship between DHA deficiency and celiac disease. DHA deficiency is a classic symptom of celiac disease that results when the level within cells is too low to meet metabolic needs of the body for this essential fatty acid.
• Relationship between DHA deficiency and features. DHA deficiency is characterized by these features:

• Worsening of the inflammatory response to gluten. Researchers found that intestinal epithelial cells sustain the celiac inflammation, releasing arachidonic acid when stimulated with gliadin and that DHA inhibits the arachidonic acid  release by these cells.⁵
• Impaired visual and cognitive development during early brain development and brain function throughout life;
• Disturbances in the function of blood clotting responses, inflammatory responses, eicosanoid production, skin integrity, insulin sensitivity, muscle health, liver health, and vascular health.⁶

How Prevalent Is DHA Deficiency In Celiac Disease and/or Gluten Sensitivity?

DHA deficiency was found to be common in study subjects with untreated celiac disease.⁷,⁸

What Are The Symptoms Of DHA Deficiency?

 DHA deficiency is marked by these symptoms:

• Aggression.
• Apathy.
• Bleeding problems (too long to clot).
• Decrease in normal visual acuity.
• Dyslexia.
• Elevated triglycerides in blood.
• Fat build-up in the liver.
• Hypertension (high blood pressure).
• Inability to concentrate.
• Long inflammatory response to infection and injury.
• Muscle loss and fatty muscles.
• Slow and/or faulty thinking called brain fog.
• In fetuses and infants, deficits in retinal structures and brain development result.
• In chronic deficiency, brain atrophy and atherosclerosis result, increasing risk of cardiovascular disease and stroke.

How Does The Body Get DHA?

• DHA should be obtained in the diet, but can be synthesized in the body from its parent fatty acid, alpha-linolenic acid provided there is adequate alpha-linolenic acid.⁹ However, alpha-linolenic acid, which comes from plants, is not a reliable means of obtaining DHA.¹⁰
• In the brain, DHA is not synthesized de novo (from scratch) or converted significantly from alpha-linolenic acid (ALA).¹¹
• Additionally, selenium deficiency can interfere with the conversion of alpha-linolenic acid into DHA when needed.

What Does DHA Do In The Body?

DHA performs a multitude of functions that include these important ones:

1. Essential for vision. Rods and cones of the retina are highly enriched in DHA.
2. Required for the normal growth and development of the fetal brain and in infants.
3. Required for producing energy in the body.
4. Balances mood.
5. Needed for skin, nail and hair health.
6. Needed for joint health.
7. Protects liver against non-alcoholic fatty liver disease.
8. Improves muscle mass and prevents muscle loss.
9. Increases sensitivity to insulin.
10. 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. Plays an essential role in the resolution phase of acute inflammation.¹²
11. Inhibits the pro-inflammatory arachidonic acid release by intestinal cells contacted by gluten.
12. Exerts a specific preventive effect against hypertension by enhancing endothelial nitric oxide synthesis to enable vessels to relax and suppressing the production of transforming growth factor-B.²
13. Inhibits the formation of TXA2, a potent vasoconstrictor (which serves to increase blood pressure) and platelet aggegator (clumps platelets), and enhances that of PGI3, a vasodilator (which serves to relax vessels) and platelet anti-aggregator.¹³
14. Exerts a preventive effect against atherosclerosis, cardiovascular heart disease and stroke by lowering triglycerides through inhibiting VLDL (very low density lipoprotein made by the liver), and apoprotein B-100 synthesis and by decreasing abnormal fat in the blood after meals.⁹,¹⁴
    However, DHA was shown NOT to counteract the inflammatory effect of arachidonic acid (an opposing omega-6 fatty acid) in already formed atherosclerotic plaque.¹⁵

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

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

Does DHA Deficiency Respond To Gluten-Free Diet?

Yes. Celiac disease-related DHA deficiency responds to a nutritious gluten free diet containing adequate DHA. Supplementation is suggested.

For brain function, direct intake of the preformed DHA is likely to be most effective, as alpha-linolenic acid to DHA conversion may be limited. Serum levels of these fatty acids in study patients increased during remission, but still remained significantly lower than control values.⁸

6 Steps To Correct DHA Deficiency:

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

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

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

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Plant Sources are Not a Source of DHA.

Highest Amounts of DHA: 

• Salmon oil, cod liver oil, menhaden oil, then herring oil.

Good Fish Choices:

• Atlantic mackerel.
• Muroaji scad.
• Bluefin tuna.
• King mackeral.
• Lake trout.
• Albacore tuna.
• Lake whitefish.
• Atlantic salmon.
• Sprat.
• Anchovy.
• Atlantic herring.
• Bluefish.
• Human milk contains DHA, but cow’s milk does not.⁹[/box]

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

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• Alcoholic drinks.
• Meat because it contains arachidonic acid, the opposing fatty acid. This does not mean you should not eat meat but rather try to balance with adequate DHA sources. For example, 3 days of the week eating omega-3 foods, 3 days eating omega-6 foods and one day vegetarian. Or you could balance these opposing fats with the same day.
• Milk products.
• Deep fried foods fried in trans-fats.

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

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Ask your doctor or pharmacist about possible interactions between DHA and medications you’re taking.

Here are common medications that interact with DHA. 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 DHA.

BILE SEQUESTRANTS

• Cholestyramine, colestipol interfere with absorption of DHA.

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.¹⁶. Includes Non-steroidal antiinflammatory drugs (NSAIDS) like Ibuprofen.

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

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• Fish oil as a source of DHA is supplied in soft gel capsules, tablets, liquid supplements.
• DHA  is supplied in soft gel capsules, tablets and oral cream supplements.
• Farm raised microalgae capsule supplements.

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

Do not use DHA supplements if:

• You are pregnant or breast-feeding.
• You have prostate cancer or are at high risk for prostate cancer (e.g., father or brother with prostate cancer).¹⁷[/box]

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

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• Arachidonic acid, an opposing omega-6 fatty acid. Check with your pharmacist.[/box]

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

RESEARCH STUDY SUMMARIES

“Docosahexaenoic acid modulates in vitro the inflammation of celiac disease in intestinal epithelial cells via the inhibition of cPLA2.” This study investigating if 1) intestinal epithelial cells have a role in the celiac inflammation, releasing  arachidonic acid (AA), a major omega-6 fatty acid, and 2) if DHA is able to modulate the celiac inflammation, down-regulating the release of AA. Researchers found that intestinal epithelial cells sustain the celiac inflammation, releasing AA when stimulated with gliadin and that DHA inhibits the AA release by these cells.

A human intestinal epithelial cell line (Caco-2) was exposed to gliadin peptides (PT-gl) (500 μg/ml) and DHA (2 μg/ml), both alone and simultaneously up to 24 hours.The exposure of those cells to PT-gl alone resulted in an increased AA release, cycloxygenase-2 expression, cPLA(2) activity and prostaglandin E(2) and interleukin-8 release in culture medium, whereas the simultaneous exposure of the cells to DHA and PT-gl prevented the above-mentioned increases.¹⁸

“Change in the fatty acid pattern of erythrocyte membrane phospholipids after oral supplementation of specific fatty acids in patients with gastrointestinal diseases.” This study shows incorporation of orally administered omega-3 fatty acids in patients with maldigestion and malabsorption may diminish inflammatory potential of the epithelial barrier. The increases in alpha-linolenic acid and DHA, as well as the conversion of alpha-linolenic acid to EPA, is attributed to the supplementation of sufficient amounts of alpha-linolenic acid and DHA, respectively.¹⁹

“Serum fatty acid profile in celiac disease patients before and after a gluten-free diet.” This study investigating profile of serum fatty acids in newly detected celiac disease before and after treatment with gluten free diet showed proportion of DHA was decreased in patients with active celiac disease. Serum levels increased during remission but still remained significantly lower than control values.²⁰

Sources:

1. Rapoport SI. Brain arachidonic and docosahexaenoic acid cascades are selectively altered by drugs, diet and disease. Prostaglandins Leukot Essent Fatty Acids. 2008 Sep-Nov;79(3-5):153-6. Epub 2008 Oct 29. [↩]
2. Richardson AJ. The importance of omega-3 fatty acids for behavior, cognition, and mood. Scandinavian Journal of Nutrition. 2003;47(2):92-8 [↩] [↩]
3. Espinosa A, Valenzuela R, González-Mañán D, D’Espessailles A, Guillermo Gormaz J, Barrera C, Tapia G. Prevention of liver steatosis through fish oil supplementation: correlation of oxidative stress with insulin resistance and liver fatty acid content. Arch Latinoam Nutr. 2013 Mar;63(1):29-36. [↩]
4. 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 [↩]
5. Vincentini O, Quaranta MG, Viora M, Agostoni C, Silano M. Docosahexaenoic acid modulates in vitro the inflammation of celiac disease in intestinal epithelial cells via the inhibition of cPLA2. Clin Nutr. 2011 Aug;30(4):541-6. doi: 10.1016/j.clnu.2011.02.007. [↩]
6. Richardson AJ. The importance of omega-3 fatty acids for behavior, cognition, and mood. Scandinavian Journal of Nutrition. 2003;47(2):92-8. [↩]
7. Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999;69(3):354-365. [↩]
8. Solakivi T, Kaukinen K, Kunnas T, Lehtimäki T, Mäki M, Nikkari ST. Serum fatty acid profile in celiac disease patients before and after a gluten-free diet. Scand J Gastroenterol. 2009;44(7):826-30. [↩] [↩]
9. Kathleen Mahan and Sylvia Escott-Stump, ed. Krause’s Food, Nutrition & Diet Therapy, 10th Edition. Philadelphia, PA. USA: W.B. Saunders Company, 2000. [↩] [↩] [↩]
10. Richardson AJ. The importance of omega-3 fatty acids for behavior, cognition, and mood. Scandinavian Journal of Nutrition. 2003;47(2):92-8 [↩]
11. Rapoport SI. Brain arachidonic and docosahexaenoic acid cascades are selectively altered by drugs, diet and disease. Prostaglandins Leukot Essent Fatty Acids. 2008 Sep-Nov; 79(3-5):153-6. [↩]
12. Nowak JZ Anti-inflammatory pro-resolving derivatives of omega-3 and omega-6 polyunsaturated fatty acids. Postepy Hig Med Dosw. 2010 Mar 17;64:115-32. [↩]
13. Das N. Long chain polyunsaturated fatty acids interacting with nitric oxide, superoxide anion, and transforming growth-B to prevent human essential hypertension. European Journal of Clinical Nutrition. 2004;58:195-203. [↩]
14. 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 [↩]
15. Solakivi T, Kunnas T, Kärkkäinen S, Jaakkola O, and Nikkari S.Arachidonic acid increases matrix metalloproteinase 9 secretion and expression in human monocytic MonoMac 6 cells. Lipids Health Dis. Mar 2009; 8: 11 [↩]
16. 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  [↩]
17. http://www.medicinenet.com/alpha-linolenic_acid-page2/supplements-vitamins.htmaccessed 12/9/12 [↩]
18. Vincentini O, Quaranta MG, Viora M, Agostoni C, Silano M. Docosahexaenoic acid modulates in vitro the inflammation of celiac disease in intestinal epithelial cells via the inhibition of cPLA2. Clin Nutr. 2011 Aug;30(4):541-6. doi: 10.1016/j.clnu.2011.02.007. [↩]
19. Siener R, Alteheld B, Terjung B, Junghans B, Bitterlich N, Stehle P, Metzner C. Change in the fatty acid pattern of erythrocyte membrane phospholipids after oral supplementation of specific fatty acids in patients with gastrointestinal diseases. Eur J Clin Nutr. 2010 Apr;64(4):410-8. [↩]
20. Solakivi T, Kaukinen K, Kunnas T, Lehtimäki T, Mäki M, Nikkari ST. Serum fatty acid profile in celiac disease patients before and after a gluten-free diet. Scand J Gastroenterol. 2009;44(7):826-30. [↩]