Vitamin E Deficiency

What Is Vitamin E?

[dropcap]V[/dropcap]itamin E is not a single vitamin but naturally occurs as a fat-soluble vitamin family that consists of at least 8 distinct molecules.

These molecules include 4 tocopherols (alpha, beta, gamma, and delta) and 4 tocotrienols (alpha, beta, gamma, and delta).

Generally, tocotrienols are more active against chronic disease while tocopherols are more protective of the nervous system.

Vitamin E (for short) is a powerful antioxidant that protects cell membranes and other fat-soluble compounds from oxidative damage by free radicals (molecules that damage cells).

Q: How does vitamin E protect cells from oxidative damage by free radicals?

A: As an example, the oxidative damage to low density cholesterol (LDL – bad type) appears to lead to the deposition of cholesterol in the arterial wall (plaque formation) leading to atherosclerotic disease, commonly called hardening of the arteries.

Regarding inflammation, mast cells are activated by oxidized LDL which results in increased expression of inflammatory cytokines. This finding suggests that vitamin E antioxidant activity in reducing oxidation of LDL lipoprotein may also reduce mast cell activation. Mast cells reside near small blood vessels and, when activated, release potent mediators involved in allergy and inflammation.¹

In neutralizing free radicals, vitamin E itself is oxidized (changed) to a free radical. Importantly, conversion of vitamin E back to the original form occurs by reaction with vitamin C. These two vital anti-oxidants go hand in hand.

Vitamin E is essential for normal cerebellar brain function (lower brain), peripheral nerve health and healthy skin.

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

• Relationship between vitamin E deficiency and celiac disease. Vitamin E deficiency is a classic symptom in celiac disease that results when the level within cells is too low to meet metabolic needs of the body for this vitamin. Blood plasma concentrations of vitamin E were found significantly lower in untreated celiac disease patients.²

• Relationship between vitamin E deficiency and inflammation. Vitamin E limits destructive inflammatory processes in cells while in the reverse, deficiency predisposes to inflammatory diseases such as celiac disease.

• Relationship between vitamin E deficiency and features. Vitamin E deficiency is characterized by these features:

1) Red blood cell fragility causing anemia due to rupturing of red blood cells;

2) Impaired clotting due to low levels of prothrombin and other clotting factors dependent on vitamin E;

3) Impaired reproduction,

4) Impaired neurologic function including balance,

5) Impaired connective tissue growth (skin, mucous membranes, bone, tendons, ligaments, blood vessels, spinal discs),

6) Impaired control of inflammation, and

7) Impaired antioxidant function.

• Relationship between vitamin E deficiency and oxidation. A study investigating the role of oxidative stress in celiac disease demonstrated that the level of markers of oxidative stress derived for both protein and lipids (oxidants) were significantly higher in asymptomatic celiac disease patients, whereas lipoproteins and vitamin E (antioxidants) were significantly lower.³

• Relationship between vitamin E deficiency and neurological complications. A case report describes diagnosing celiac disease in a patient with neurological manifestations including myopathy (inflammatory infiltrates and rimmed vacuoles, similar to those found in inclusion-body myositis), polyneuropathy, and ataxia due to severe vitamin E deficiency. A gluten-free diet and vitamin E supplementation reversed both the clinical neurological manifestations and the abnormalities in the muscle biopsy. “This case illustrates the spectrum of neurological complications of celiac disease and documents the occurrence of reversible pathology resembling inclusion-body myopathy in the muscle.”⁴

• Relationship between vitamin E deficiency and common variable immunodeficiency disease (CVID).  Patients with CVID having free radical caused nerve damage induced by vitamin E deficiency who have evidence of enteropathy should be screened for vitamin E deficiency, as early detection and consequent treatment may prevent, halt or reverse the neurological problems that can develop.⁵

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

Vitamin E deficiency is common in patients with untreated celiac disease.⁶

A retrospective medical record review of 83 pediatric patients with a confirmed diagnosis of celiac disease and who had fat-soluble vitamin levels measured at diagnosis between 1995 and 2012 at Mayo Clinic showed that 2 patients (2.4%) had vitamin E deficiency.⁷

What Are The Symptoms Of Vitamin E Deficiency?

Vitamin E deficiency is marked by these symptoms:

• Peripheral neuropathy.
• Muscle weakness.
• Abnormal clotting.
• Anemia.
• Eczema.
• Loss of deep tendon reflexes.
• Impaired vibratory and sensory sensations.
• Impaired balance and coordination.
• Involuntary eye movements.
• Hardening of the arteries.
• Damage to eye retina.
• Retrolental fibroplasia (eye disease).
• Increased risk of cancer.
• Infertility in males can occur.
• In females, dysmenorrhea and reproductive disorders occur.
• In infants, irritability and fluid retention occur.

How Does The Body Get Vitamin E?

• Vitamin E is absorbed in the upper small intestine by highly variable micelle-dependent diffusion.⁸
• Absorption of vitamin E requires dietary fat.

What Does Vitamin E Do In The Body?

1. Supports immune function (protecting thymic function and white blood cells from oxidative stress).
2. Protects against cardiovascular disease
3. Protects against cataracts.
4. Protects against macular degeneration.
5. Exerts a direct effect on the control of inflammation.
6. Red and white blood cell production.
7. Required for connective tissue growth.
8. Required for genetic control of cell division.
9. Stabilizes cell membranes for strength.
10. Inhibits abnormal adhesion or clumping of platelets (cells that form clots). It does this by increasing the expression of two enzymes that suppress arachidonic acid metabolism (a major omega-6 fatty acid), thereby increasing the release of prostacyclin from the endothelium, which, in turn, dilates blood vessels and inhibits platelet aggregation.⁹
11. In males, supports the correct differentiation and function of epidydimal epithelium, spermatid maturation and secretion of proteins by the prostate.¹⁰

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

• Vitamin E deficiency in celiac disease results from malabsorption due to gluten enteropathy.

Does Vitamin E Deficiency Respond To Gluten-Free Diet?

Yes. Celiac disease-related vitamin E deficiency responds to gluten free diet that is adequate in vitamin E.

Supplementation is suggested.  “Vitamin E correction may offer benefit to newly diagnosed and those who fail to adhere to strict gluten free diet.”²

6 Steps To Correct Vitamin E Deficiency:

• [dropcap]1[/dropcap]Meet, or Exceed the RDA (Recommended Dietary Allowances) for Vitamin E in IU per day:

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6 IU for infants 0-6 months; 7.5 IU for infants 5-12 months.

9 IU for children 1-3 years.

10.4 IU for children 4-8 years; 16.4 IU for children 9-13 years.

22.4 IU for males and females over 14 years.

22.4 IU for pregnancy; 28.4 IU for lactation.

The amount of vitamin E required is dependent upon the amount of polyunsaturated fat in the diet. The more polyunsaturated fat in the diet (omega-6), the greater the risk for oxidative damage, and the vitamin E requirement is increased.[/box]

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

Tocopherols are the major vitamin E components present in most vegetable oils while palm fruit is the richest source of tocotrienols among all vegetable oils. Palm fruit contains both tocopherols (30%) and tocotrienols  (70%) as do rice grain, coconut oil, and annatto seed.  Other sources of tocotrienols include grape fruit seed oil, hazelnuts, maize, olive oil, buckthorn berry, flax seed oil, poppy seed oil and sunflower oil.¹¹

Food Sources of Vitamin E ranked by milligrams of vitamin E per standard amount; also calories in the standard amount. (All provide ≥ 10% of RDA for vitamin E for adults, which is 15 mg a-tocopherol [AT]/day.)

Food, Standard Amount	AT (mg)	Calories
Sunflower seeds, dry roasted, 1 oz.	7.4	165
Almonds, 1 oz.	7.3	164
Sunflower oil, high linoleic, 1 Tbsp.	5.6	120
Cottonseed oil, 1 Tbsp.	4.8	120
Safflower oil, high oleic, 1 Tbsp.	4.6	120
Hazelnuts (filberts), 1 oz.	4.3	178
Mixed nuts, dry roasted, 1 oz.	3.1	168
Turnip greens, frozen, cooked, ½ cup	2.9	24
Tomato paste, ¼ cup	2.8	54
Pine nuts, 1 oz.	2.6	191
Peanut butter, 2 Tbsp.	2.5	192
Tomato puree, ½ cup	2.5	48
Tomato sauce, ½ cup	2.5	39
Canola oil, 1 Tbsp.	2.4	124
Peanuts, 1 oz.	2.2	166
Avocado, raw, ½ avocado	2.1	161
Carrot juice, canned, ¾ cup	2.1	71
Peanut oil, 1 Tbsp.	2.1	119
Corn oil, 1 Tbsp.	1.9	120
Olive oil, 1 Tbsp.	1.9	119
Spinach, cooked, ½ cup	1.9	21
Dandelion greens, cooked, ½ cup	1.8	18
Sardine, Atlantic, in oil, drained, 3 oz.	1.7	177
Blue crab, cooked/canned, 3 oz.	1.6	84
Brazil nuts, 1 oz.	1.6	186
Herring, Atlantic, pickled, 3 oz.	1.5	222

Source: Nutrient values from Agricultural Research Service (ARS) Nutrient Database for Standard Reference, Release 17. Foods are from ARS single nutrient reports, sorted in descending order by nutrient content in terms of common household measures.

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

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• Refined vegetable oils degrade vitamin E. Instead, use cold-pressed oils which retain all the nutrients.
• Olestra (a fat substitute found in snacks foods like potato chips) inhibits absorption of vitamin E.

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

[box type=”shadow” ]Here are common medications that deplete vitamin E. 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.

CARDIOVASCULAR DRUGS

• Beta blockers (Inderol® [Propranolol], Lopressor®, Corgard®, Atenolol®) – vitamin E interferes with their absorption.

CHOLESTEROL DRUGS

• (Colestid® and Questran®) interfere with absorption of vitamin E.

LAXATIVES

• Metamucil, FiberCon, Citrucel, Colace, Glycolax, Milk of Magnesia, Dulcolax.

WEIGHT LOSS DRUGS THAT BIND FAT 

• Zenicol (Orlistat®) interfere with absorption of vitamin E.

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

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• A blood level concentration should be obtained to determine status before supplementing.
• Vitamin E is available in many different formulations, either natural or synthetic…choose natural.
• The biologically active form of the vitamin is the d- form (d-alpha-tocopherol) and it is recommended for supplementation over the dl- (synthetic) forms because synthetic forms are half as active as the natural d- form.
• Synthetic dl-alpha-tocopherol does not provide any anti-oxidant protection.

Toxicity: Supplemental doses of up to 1,000 mg/day (1,500 IU/day of the natural form or 1,100 IU/day of the synthetic form) in adults appear to be safe. Toxic effects involve risk of hemorrhage.[/box]

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

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• The iron supplements ferrous sulfate and ferric chloride (not ferrous fumarate or ferrous gluconate) can damage vitamin E. Check with your pharmacist.[/box]

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

RESEARCH STUDY SUMMARIES

“Is it necessary to assess for fat-soluble vitamin deficiencies in pediatric patients with newly diagnosed celiac disease?” This retrospective medical record review of 83 pediatric patients with a confirmed diagnosis of celiac disease and fat-soluble vitamin levels measured at diagnosis between 1995 and 2012 at Mayo Clinic showed that 2 patients had vitamin E deficiency. Both patients with vitamin E deficiency were symptomatic and had complete villous atrophy.

Patients’ demographics, fat-soluble vitamin levels, and pertinent clinical factors at the time of diagnosis were collected from the charts of 51 girls and 32 boys, with an average age at diagnosis of 12.8 years in girls and 13.0 years in boys.

The most commonly reported symptoms were abdominal pain in 49 patients and diarrhea in 30 patients. Family history of celiac disease was reported in 32 patients. Average vitamin levels for vitamin E, 25-hydroxyvitamin D (25 (OH) D), and vitamin A were 7.5 mg/L, 32.8 ng/mL, and 334.5 μg/dL, respectively. None of the patients were receiving vitamin supplements at the time of diagnosis.⁷

“A randomized controlled trial of vitamin E in the treatment of primary dysmenorrhea.” This study investigating vitamin E in the treatment of dysmenorrhea demonstrated that vitamin E relieves the pain of primary dysmenorrhea and reduces blood loss.¹²

“Vitamin E levels in patients with celiac disease.” This study investigating vitamin E status in patients with active celiac disease and patients on a GFD demonstrated that plasma concentrations of vitamin E were significantly lower in untreated celiac disease patients. Vitamin E correction may offer benefit to newly diagnosed and those who fail to adhere to strict GF diet.¹³

“Oxidative stress in subjects affected by celiac disease.” This study investigating the role of oxidative stress in celiac disease demonstrated that the level of markers of oxidative stress derived for both protein (carbonyl groups) and lipids (thiobarbituric acid-reactive substances) were significantly higher in asymptomatic celiac disease patients, whereas lipoproteins and alpha-tocopherol were significantly lower. These data indicate that in celiac disease even when asymptomatic, a redox imbalance persists, probably due to malabsorption.¹⁴

CASE REPORT SUMMARIES

“Reversible inflammatory and vacuolar myopathy with vitamin E deficiency in celiac disease.” This case report describes diagnosing celiac disease in a patient with neurological manifestations including myopathy, polyneuropathy, and ataxia. Laboratory investigations showed anti-gliadin antibodies and severe vitamin E deficiency. Muscle biopsy revealed inflammatory infiltrates and rimmed vacuoles, similar to those found in inclusion-body myositis.

A gluten-free diet and vitamin E supplementation reversed both the clinical neurological manifestations and the abnormalities in the muscle biopsy. Anti-gliadin antibodies were no longer present. “This case illustrates the spectrum of neurological complications of celiac disease and documents the occurrence of reversible pathology resembling inclusion-body myopathy in the muscle.”⁴

“Vitamin E deficiency induced neurological disease in common variable immunodeficiency: two cases and a review of the literature of vitamin E deficiency.” This case report describing diagnosis of celiac disease in 2 patients with common variable immunodeficiency disease (CVID) having free radical mediated neuronal damage induced by vitamin E deficiency recommends all CVID patients with evidence of enteropathy should be screened for vitamin E deficiency, as early detection and consequent treatment may prevent, halt or reverse the neurological sequelae.¹⁵

Sources:

1. Shaik-Dasthagirisaheb YB, Varvara G, Murmura G, Saggini A, Caraffa A, Antinolfi P, Tete’ S, Tripodi D, Conti F, Cianchetti E, Toniato E, Rosati M, Speranza L,Pantalone A, Saggini R, Tei M, Speziali A, Conti P, Theoharides TC, Pandolfi F. Role of vitamins D, E and C in immunity and inflammation. J Biol Regul Homeost Agents. 2013 Apr-Jun;27(2):291-5. [↩]
2. Hozyasz KK, Chelchowska M, Laskowska-Klita T. Vitamin E levels in patients with celiac disease. Medycryna Wieku Rozwojowego. Oct-Dec 2003; 7(4 Pt 2):593-604. [↩] [↩]
3. Odetti F, Valentini S, Aragno I, Garibaldi S, Pronzato MA, Rolandi E, Barecca T. Oxidative stress in subjects affected by celiac disease. Free Radical Research. Jul 1998; 29(1);17-24. [↩]
4. Kleopa KA, Kyriacou K, Zamba-Papanicolaou E, Kyriakides T. Reversible inflammatory and vacuolar myopathy with vitamin E deficiency in celiac disease. Muscle Nerve. 2005 Feb;31(2):260-5. [↩] [↩]
5. Aslam A, Misba SA, Talbot K, Chapel H. Vitamin E deficiency induced neurological disease in common variable immunodeficiency: two cases and a review of the literature of vitamin E deficiency. Clinical Immunology. Jul 2004; 112(1): 24-9. [↩]
6. Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999; 69(3):354-365. [↩]
7. Imam MH1, Ghazzawi Y, Murray JA, Absah I. Is it necessary to assess for fat-soluble vitamin deficiencies in pediatric patients with newly diagnosed celiac disease? J Pediatr Gastroenterol Nutr. 2014 Aug;59(2):225-8. doi: 10.1097/MPG.0000000000000368. [↩] [↩]
8. Kathleen Mahan and Sylvia Escott-Stump, ed. Krause’s Food, Nutrition & Diet Therapy, 10th Edition. Philadelphia, PA. USA: W.B. Saunders Company, 2000. [↩]
9. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. [↩]
10. Stazi AV, Mantovani A. A risk factor for female fertility and pregnancy: celiac disease. Gynecological Endocrinology. Dec 2000; 14 (6):454-63. [↩]
11. Ahsan H, Ahad A, Siddiqui WA. A review of characterization of tocotrienols from plant oils and foods. J Chem Biol. 2015 Jan 20;8(2):45-59. doi: 10.1007/s12154-014-0127-8. [↩]
12. Ziaei S, Zakeri M, Kazemnejad A. A randomized controlled trial of vitamin E in the treatment of primary dysmenorrhea. BJOG: An International Journa of Obstetrics and Gynecology. Apr 2005; 112(4):466-9. [↩]
13. Hozyasz KK, Chelchowska M, Laskowska-Klita T. Vitamin E levels in patients with celiac disease. Medycryna Wieku Rozwojowego. Oct-Dec 2003; 7(4 Pt 2):593-604. [↩]
14. Odetti F, Valentini S, Aragno I, Garibaldi S, Pronzato MA, Rolandi E, Barecca T. Oxidative stress in subjects affected by celiac disease. Free Radical Research. Jul 1998; 29(1);17-24. [↩]
15. Aslam A, Misba SA, Talbot K, Chapel H. Vitamin E deficiency induced neurological disease in common variable immunodeficiency: two cases and a review of the literature of vitamin E deficiency. Clinical Immunology. Jul 2004; 112(1): 24-9. [↩]