Vitamin E Deficiency

Etiology

In developed countries, it is unlikely that vitamin E deficiency occurs due to diet intake insufficiency, and the more common causes are below.

• Premature low birth weight infants with a weight less than 1500 grams (3.3 pounds)
• Mutations in the tocopherol transfer protein causing impaired fat metabolism
• Disrupted fat malabsorption as the small intestine requires fat to absorb vitamin E
• Patients with cystic fibrosis patients fail to secrete pancreatic enzymes to absorb vitamins A, D, E, and K
• Short-bowel syndrome patients may take years to develop symptoms. Surgical resection, mesenteric vascular thrombosis, and pseudo-obstruction are a few examples of this issue
• Chronic cholestatic hepatobiliary disease leads to a decrease in bile flow and micelle formation that is needed for vitamin E absorption
• Crohn's disease, exocrine pancreatic insufficiency, and liver disease may all not absorb fat
• Abetalipoproteinemia an autosomal-recessive disease, causes an error in lipoprotein production and transportation
• Isolated vitamin E deficiency syndrome an autosomal recessive disorder of chromosome arm 8q

In developing countries, the most common cause is inadequate intake of vitamin E.

Epidemiology

Serum levels of alpha-tocopherol in 0.1% of United States adults over the age of 20 have been found to be deficient. Surveys of the same data set have shown that 89.8% of men and 96.3% of women 19 years of age or older have insufficient intake of alpha-tocopherol. Some studies have shown alpha-tocopherol to be lower in pediatric populations and higher in pregnancy.[5]

Pathophysiology

Vitamin E works as an antioxidant, immunomodulation, and antiplatelet effects.

Antioxidant Effect

Vitamin E prevents propagated oxidation of saturated fatty acids within membranes. Also, vitamin E may prevent oxidative changes to LDLs, reducing coronary heart diseases.

Immunomodulation

Vitamin E decreases the production of prostaglandin E2 and serum lipid peroxides while enhancing lymphocyte proliferation.

Antiplatelet Effect

Vitamin E inhibits platelet adhesion by preventing oxidative changes to LDLs and inhibition of platelet aggregation by reducing prostaglandin E2. Another effect is inhibiting protein kinase C causing smooth-muscle proliferation.

Even though research has shown that vitamin E assists with the prevention of heart disease and atherosclerosis, it has not been approved for this use by the United States Food and Drug Administration (FDA).

History and Physical

Patients may present with one of the causative histories listed, along with symptoms of ataxia, difficulty with upward gaze, and hyporeflexia. Not as common symptoms include muscle weakness and visual-field constriction. The most severe symptoms are blindness, dementia, and cardiac arrhythmias.

If vitamin E deficiency is expected, a full neurological exam is recommended as well as a standard physical exam. Patients presenting early may show hyporeflexia, decreased night vision, loss/decreased vibratory sense; however, they have normal cognition. A more moderate stage of this deficiency may show limb and truncal ataxia, profuse muscle weakness, and limited upward gaze. Late presentations may show cardiac arrhythmias and possible blindness with reduced cognition. Ataxia is the most common exam finding.

Patients that have abetalipoproteinemia have eye problems, often including pigmented retinopathy and visual field issues. However, patients suffering from cholestatic liver disease often have personality and behavioral disorders.

Evaluation

A low alpha-tocopherol level or low ratio serum alpha-tocopherol to serum lipids measurement is the mainstay of diagnosis. In adults, alpha-tocopherol levels should be less than 5 mcg/mL. In an adult with hyperlipidemia, the abnormal lipids may affect the vitamin E levels and a serum alpha-tocopherol to lipids level, needing to be less than 0.8 mg/g) is more accurate. A pediatric patient with abetalipoproteinemia will have serum alpha-tocopherol levels that are not detectable.

Treatment / Management

Treatment addresses the underlying cause of the deficiency (fat malabsorption, fat metabolism disorders, among others) and then provides oral vitamin E supplementation. Also, a modification in diet can assist in the supplementation, increase intake of leafy vegetables, whole grains, nuts, seeds, vegetable oils, and fortified cereals is highly recommended. Though normally presented in our diets, adults need 15mg of vitamin E per day. A supplement of 15 to 25 mg/kg once per day or mixed tocopherols 200 IU can both be used. If a patient has issues with the small intestine and/or oral ingestion intramuscular injection is necessary.[6][7][8][9] The recommended daily allowance of alpha-tocopherol is as follows.(B2)

• Age 0 to 6 months: 3 mg
• Age 6 to 12 months: 4 mg
• Age 1 to 3 years: 6 mg
• Age 4 to 10 years: 7 mg
• Adults and elderly patients: 10 mg

Differential Diagnosis

While developing a differential diagnosis, clinicians must consider other possible vitamin deficiencies as well as the following: 

• Friedreich ataxia
• Ataxia with vitamin E deficiency (AVED)
• Stroke
• Cerebral palsy
• Paraneoplastic syndrome
• Biliary disease
• Short-Bowl syndrome
• Mutations in the tocopherol transfer protein causing impaired fat metabolism 
• Cystic fibrosis 
• Chronic cholestatic hepatobiliary disease 
• Crohn disease
• Exocrine pancreatic insufficiency
• Liver disease 
• Abetalipoproteinemia
• Isolated vitamin E deficiency

Prognosis

If left untreated, symptoms may worsen. However, once diagnosed, the outcome is very good as most symptoms will resolve quickly. However, as the deficiency becomes more pronounced, the therapy will be more restricted. Patients who are at risk for vitamin E deficiency should be tested and evaluated regularly.

Complications

Vitamin E has a few interactions with medications that are listed below:

• Anticoagulation and antiplatelet medications: due to vitamin E inhibiting platelet aggregation and disrupting vitamin K clotting factors, there is a protentional increase risk of bleeding combining these two.
• Simvastatin and niacin: Vitamin E can reduce the amount of high-density lipoprotein (HDL), which is the opposite desired effect of taking simvastatin and/or niacin.