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VITAMIN E

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Vitamin E, alpha-tocopherol, is a fat-soluble vitamin.

Specific Substances

    1) (ALL-R)-alpha-tocopherol
    2) (2R,4'R,8'R)-alpha-tocopherol
    3) Alpha-tocopherol
    4) D-alpha tocopherol
    5) D-alpha tocopheryl acid succinate
    6) Dl-alpha tocopheryl acetate
    7) Dl-alpha tocopheryl acid succinate
    8) D-alpha tocopheryl acetate
    9) Mixed tocopherol
    10) Molecular Formula: C29-H50-O2
    11) CAS 59-02-9 (vitamin E)
    12) CAS 58-95-7 (alpha-tocopherol acetate)
    13) Tocofersolan

Available Forms Sources

    A) FORMS
    1) Vitamin E is available as follows: 400 International Unit capsules; 10 International Units, 100 International Units, 200 International Units, and 400 International Unit gelatin capsules; and 50 International Units/mL oral drops (Aquasol E; Natural E vitamin). It is also available in combination with other vitamins, minerals, protein supplements and infant formulas (HSDB , 2001).
    2) TOCOPHEROL EQUIVALENTS (Farrell & Roberts, 1994):
    1) 1 mg dl-alpha tocopheryl acetate = 1 International Unit
    2) 1 mg dl-alpha tocopherol = 1.1 International Units
    3) 1 mg d-alpha tocopheryl acetate = 1.36 International Units
    4) 1 mg d-alpha tocopherol = 1.49 International Units
    5) 1 mg d-alpha tocopheryl acid succinate = 1.21 International Units
    6) 1 mg dl-alpha tocopheryl acid succinate = 0.89 International Units
    3) TOCOFERSOLAN: Each mL contains 50 mg of d-alpha-tocopherol (Prod Info Vedrop oral solution, 2012).
    B) SOURCES
    1) Vitamin E is found in many foods such as wheat germ oil, vegetable oils, cereal grains, animal fats, meat, poultry, eggs, fruits, and vegetables (HSDB , 2001; Jellin et al, 2000).
    C) USES
    1) Vitamin E has been used for many conditions including malabsorption disorders, hematologic disorders, ocular disorders, cardiovascular disease, and Alzheimer's disease and other dementias (Jellin et al, 2000). Subsequent work has failed to confirm a benefit in reducing the risk of dementia (Danielle et al, 2002).
    a) Tocofersolan is indicated in pediatric patients (full term infants to 18 years of age) with vitamin E deficiency due to digestive malabsorption with congenital chronic cholestasis or hereditary chronic cholestasis (Prod Info Vedrop oral solution, 2012).
    2) It has also been used in the prevention of numerous conditions (eg, obstetrics {infertility, preventing preeclampsia in high-risk women}, pre- and postmenopausal symptoms, aging effects, inflammatory skin conditions, and neuromuscular disorders) (Jellin et al, 2000).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Vitamin E, an antioxidant, is an essential nutrient. It is thought to have a role in the normal function of the nervous, reproductive, muscular, cardiovascular, and hematopoietic systems. Vitamin E has been used for a variety of conditions (ie, hemolytic anemia, claudication, wound healing, adult respiratory distress syndrome), despite a lack of evidence supporting efficacy.
    B) PHARMACOLOGY: Vitamin E preferentially binds to peroxyl radicals and forms the corresponding organic hydroperoxide and tocopheroxyl radical, which then interacts with other antioxidant compounds (ie, ascorbic acid) to generate tocopherol. It may also be responsible for cell growth and proliferation.
    C) TOXICOLOGY: In high dose (greater than 1000 mg/day) it may antagonize the effect of vitamin K. In addition, it may have a pro-oxidant effect, and may also displace other antioxidants potentially increasing the risk for oxidative damage.
    D) EPIDEMIOLOGY: Overdose is uncommon, significant toxicity is rare.
    E) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Vitamin E is usually well tolerated. Fatigue, weakness, headache, nausea, diarrhea, flatulence, and abdominal pain may occur with large doses. An increased bleeding tendency has been observed in patients deficient in vitamin K following large doses of vitamin E. INFREQUENT: Retinal and intraventricular hemorrhages and necrotizing enterocolitis have been observed in premature infants receiving vitamin E.
    2) TOPICAL: Contact dermatitis and erythema multiforme has been rarely reported with topical vitamin E use.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Events are anticipated to be an extension of adverse effects at high dose (or long-term therapy) and may include: fatigue, weakness, headache, nausea, diarrhea, flatulence, and abdominal pain.
    2) SEVERE TOXICITY: Coagulopathies may develop in patients with vitamin K-deficiencies or those receiving warfarin. Bleeding may occur. RARE: Hemorrhagic stroke.
    0.2.20) REPRODUCTIVE
    A) Vitamin E is classified as FDA pregnancy category A. Nutritional supplement doses of vitamins and minerals are generally considered safe during pregnancy.

Laboratory Monitoring

    A) Monitor fluid and electrolyte status in patients with severe diarrhea.
    B) Follow INR or prothrombin time (PT) with symptomatic chronic overdose or in patients with a large acute ingestion with evidence of a coagulopathy.
    C) Serum vitamin E levels may be useful in confirming a suspected diagnosis of an acute or chronic excessive ingestion. However, levels are not useful to guide therapy.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Significant toxicity is not anticipated. Monitor fluid status in patients that develop moderate diarrhea; antidiarrheals may be indicated.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Monitor coagulation studies (eg, INR, PT) following a large dose or patients at risk (eg on warfarin, other anticoagulants or anti-platelet agents, or risk of vitamin K deficiency). High doses (exact dose unknown; but likely exceeding 400 IU/day) of vitamin E may increase the risk of bleeding when combined with anticoagulant or antiplatelet agents. In large doses, vitamin E can inhibit platelet aggregation and antagonize vitamin K-dependent clotting factors. Monitor for bleeding.
    C) DECONTAMINATION
    1) PREHOSPITAL: Significant toxicity is not anticipated after ingestion. Gastrointestinal decontamination is not indicated unless coingestants are suspected.
    2) HOSPITAL: Significant toxicity is not anticipated after ingestion. Treatment is symptomatic and supportive. Gastrointestinal decontamination is not indicated unless coingestants are suspected.
    D) PATIENT DISPOSITION
    1) HOME CRITERIA: An asymptomatic adult or child with an inadvertent minor exposure (eg, a single dietary supplement ingested by a young child) may be monitored at home.
    2) OBSERVATION CRITERIA: Patients with a deliberate self-harm ingestion should be evaluated in a healthcare facility and monitored for symptoms. Patients may be discharged to home, if no symptoms develop or symptoms have resolved and laboratory studies are within normal limits.
    3) ADMISSION CRITERIA: Patients currently receiving warfarin therapy or a history of vitamin K deficiency may be at risk to develop bleeding. Patients with active bleeding should be monitored and treated as needed. Patients may be discharged to home once symptoms have resolved and laboratory studies are within normal limits.
    4) CONSULT CRITERIA: Contact a medical toxicologist or Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear. Patients with a deliberate self-harm ingestion should be evaluated by a mental health specialist.

Range Of Toxicity

    A) TOXICITY: A minimum toxic dose has not been established. Vitamin E plasma concentrations greater than 3.5 mg/dL may result in toxicity. Doses of 2000 to 2500 international units/day or more can produce gastrointestinal distress. In a meta-analysis, mortality (from all causes) may increase at doses of greater than 400 International Units/day (greater than 400 mg/day). Daily intake of 200 to 600 mg of vitamin E is innocuous in most people; however, long-term use of doses over 400 units/day has caused diarrhea, nausea, flatulence, or stomach cramps in some patients.
    B) THERAPEUTIC DOSE: RECOMMENDED DIETARY ALLOWANCES: 0 to 6 months: 6 (4 mg) International Units/day; 7 to 12 months: 7.5 (5 mg) International Units/day; 1 to 3 years: 9 (6 mg) International Units/day; 4 to 8 years: 10.4 (7 mg) International Units/day; 9 to 13 years: 16.4 (11 mg) International Units/day and 14 years and older: 22.4 (15 mg) International Units/day.
    C) TOCOFERSOLAN: PEDIATRIC: Recommended daily dose in patients with congenital or hereditary chronic cholestasis is 0.34 mL/kg/day (or 17 mg/kg/day of d-alpha-tocopherol in the form of tocofersolan).

Clinical Effects

Summary Of Exposure

    A) USES: Vitamin E, an antioxidant, is an essential nutrient. It is thought to have a role in the normal function of the nervous, reproductive, muscular, cardiovascular, and hematopoietic systems. Vitamin E has been used for a variety of conditions (ie, hemolytic anemia, claudication, wound healing, adult respiratory distress syndrome), despite a lack of evidence supporting efficacy.
    B) PHARMACOLOGY: Vitamin E preferentially binds to peroxyl radicals and forms the corresponding organic hydroperoxide and tocopheroxyl radical, which then interacts with other antioxidant compounds (ie, ascorbic acid) to generate tocopherol. It may also be responsible for cell growth and proliferation.
    C) TOXICOLOGY: In high dose (greater than 1000 mg/day) it may antagonize the effect of vitamin K. In addition, it may have a pro-oxidant effect, and may also displace other antioxidants potentially increasing the risk for oxidative damage.
    D) EPIDEMIOLOGY: Overdose is uncommon, significant toxicity is rare.
    E) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: Vitamin E is usually well tolerated. Fatigue, weakness, headache, nausea, diarrhea, flatulence, and abdominal pain may occur with large doses. An increased bleeding tendency has been observed in patients deficient in vitamin K following large doses of vitamin E. INFREQUENT: Retinal and intraventricular hemorrhages and necrotizing enterocolitis have been observed in premature infants receiving vitamin E.
    2) TOPICAL: Contact dermatitis and erythema multiforme has been rarely reported with topical vitamin E use.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Events are anticipated to be an extension of adverse effects at high dose (or long-term therapy) and may include: fatigue, weakness, headache, nausea, diarrhea, flatulence, and abdominal pain.
    2) SEVERE TOXICITY: Coagulopathies may develop in patients with vitamin K-deficiencies or those receiving warfarin. Bleeding may occur. RARE: Hemorrhagic stroke.

Heent

    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) Vitamin E, when used to treat retinopathy in low-birth-weight premature infants, has been implicated in retinal and intraventricular hemorrhages (Phelps et al, 1987).
    2) Long-term use of doses greater than 400 to 800 Units/day has been associated with blurred vision (HSDB , 2001).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH THERAPEUTIC USE
    a) Long-term use of doses greater than 400 to 800 Units/day may cause dizziness, headache, fatigue, or weakness (S Sweetman , 2001; HSDB , 2001).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) ENTEROCOLITIS
    1) WITH THERAPEUTIC USE
    a) A 2-fold increase in necrotizing enterocolitis occurred in low-birth-weight infants (eg, less than 1500 g) who received long-term treatment with dl-alpha-tocopherol up to 30 mg/kg/day administered orally or intravenously (S Sweetman , 2001; Meyers et al, 1996).
    B) DRUG-INDUCED GASTROINTESTINAL DISTURBANCE
    1) WITH THERAPEUTIC USE
    a) Several adults given repeated doses of 2 to 3 g/day developed mild gastrointestinal irritation with diarrhea. Long-term use of doses greater than 400 to 800 Units/day caused diarrhea, nausea, flatulence, or stomach cramps (S Sweetman , 2001; HSDB , 2001).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) BLOOD COAGULATION DISORDER
    1) WITH THERAPEUTIC USE
    a) Prolonged prothrombin time, INR, and clotting time have been observed. Long-term use of doses greater than 800 Units/day have been associated with increased bleeding tendencies in patients deficient in vitamin K (HSDB , 2001; S Sweetman , 2001).
    b) It is suggested that excessive use may antagonize vitamin K function and inhibit prothrombin production (HSDB , 2001). In one study, more deaths from hemorrhagic stroke and fewer from ischemic heart disease were observed among participants who received alpha-tocopherol than among those who did not (Liede et al, 1998).
    c) Alpha-tocopherol supplementation may increase the risk of gingival bleeding (Liede et al, 1998).
    d) Vitamin E, when used to treat retinopathy in low-birth-weight premature infants, has been associated with an increased incidence of retinal and intraventricular hemorrhages (Phelps et al, 1987).
    1) Infants receiving vitamin E had a significantly greater incidence of retinal hemorrhage than did those on placebo (Phelps et al, 1987).
    2) An increased incidence of intraventricular hemorrhage was observed in low-birth-weight (less than 1 kg) premature infants administered vitamin E (Phelps et al, 1987).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) CONTACT DERMATITIS
    1) WITH THERAPEUTIC USE
    a) Topical application of pure vitamin E oil was associated with the development of erythematous and eczematous eruptions in a 63-year-old woman. Positive skin test reactions were noted at 48 hours (Goldman & Rapaport, 1986).
    b) A severe dermatitis occurred in patients using topical vitamin E after a chemical peel or dermabrasion of the face (Hunter & Frumkin, 1991).
    c) A 19-year-old woman developed eczematous lesions following the use of a cosmetic cream containing vitamin E and vitamin A (Bazzano et al, 1996).
    B) ERYTHEMA MULTIFORME
    1) WITH THERAPEUTIC USE
    a) Topical use of a vitamin E cream on scar tissue produced generalized erythema multiforme reaction in 2 patients (Saperstein et al, 1984).

Reproductive

    3.20.1) SUMMARY
    A) Vitamin E is classified as FDA pregnancy category A. Nutritional supplement doses of vitamins and minerals are generally considered safe during pregnancy.
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Vitamin E is classified as pregnancy category A (Briggs et al, 1998).
    2) Nutritional supplement doses of vitamins and minerals are generally considered safe during pregnancy. Daily dietary vitamin E requirements are the same during pregnancy (dietary reference intake of 15 mg alpha-tocopherol equivalents) as those recommended in adult women who are not pregnant (Picciano, 2003).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation in humans.
    3.20.5) FERTILITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects on fertility from exposure to this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor fluid and electrolyte status in patients with severe diarrhea.
    B) Follow INR or prothrombin time (PT) with symptomatic chronic overdose or in patients with a large acute ingestion with evidence of a coagulopathy.
    C) Serum vitamin E levels may be useful in confirming a suspected diagnosis of an acute or chronic excessive ingestion. However, levels are not useful to guide therapy.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor fluid and electrolyte status in patients with severe diarrhea.
    2) Serum vitamin E levels may be useful in confirming the suspected diagnosis of acute and chronic excessive ingestion.
    a) Therefore, elevated levels in the presence of a history of excessive intake and/or symptoms can only confirm what is suspected. Levels are not useful to guide treatment.
    3) Blood levels greater than 3.5 mg percent may be associated with a higher incidence of necrotizing enterocolitis in premature infants (Bieri et al, 1983).
    B) COAGULATION STUDIES
    1) Follow INR or prothrombin time (PT) with symptomatic chronic overdose or in patients with evidence of a coagulopathy.

Methods

    A) CHROMATOGRAPHY
    1) High-performance liquid chromatography may be used to determine vitamin E levels in serum and plasma (HSDB , 2001).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients currently receiving warfarin therapy or a history of vitamin K deficiency may be at risk to develop bleeding. Patients with active bleeding should be monitored and treated as needed. Patients may be discharged to home once symptoms have resolved and laboratory studies are within normal limits.
    6.3.1.2) HOME CRITERIA/ORAL
    A) An asymptomatic adult or child with an inadvertent minor exposure (eg, a single dietary supplement ingested by a young child) may be monitored at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Contact a medical toxicologist or Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear. Patients with a deliberate self-harm ingestion should be evaluated by a mental health specialist.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate self-harm ingestion should be evaluated in a healthcare facility and monitored for symptoms. Patients may be discharged to home, if no symptoms develop or there is no evidence of coagulopathy in patients at risk.

Monitoring

    A) Monitor fluid and electrolyte status in patients with severe diarrhea.
    B) Follow INR or prothrombin time (PT) with symptomatic chronic overdose or in patients with a large acute ingestion with evidence of a coagulopathy.
    C) Serum vitamin E levels may be useful in confirming a suspected diagnosis of an acute or chronic excessive ingestion. However, levels are not useful to guide therapy.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Toxicity has not been reported after acute overdose. Gastrointestinal decontamination is generally not necessary unless coingestants are suspected.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Significant toxicity is not anticipated after ingestion and gastrointestinal decontamination is generally not necessary.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Treatment is symptomatic and supportive; significant toxicity is not anticipated.
    2) Monitor coagulation studies (eg, INR, PT) following a large dose or in the patient at high risk (eg on warfarin, other anticoagulants or anti-platelet agents, or risk of vitamin K deficiency). High doses (exact dose unknown; but likely exceeding 400 IU/day) of vitamin E may increase the risk of bleeding when combined with anticoagulant or antiplatelet agents (Office of Dietary Supplements, 2011).
    B) MONITORING OF PATIENT
    1) Monitor fluid and electrolyte status in patients with significant diarrhea and/or vomiting.
    2) Follow INR or prothrombin time (PT) with symptomatic chronic overdose or patients at risk to develop a coagulopathy (ie, warfarin therapy or other anticoagulant; vitamin K deficiency) (Office of Dietary Supplements, 2011).

Enhanced Elimination

    A) LACK OF INFORMATION
    1) It is unknown if enhanced elimination could be beneficial following an acute ingestion.

Range Of Toxicity

Summary

    A) TOXICITY: A minimum toxic dose has not been established. Vitamin E plasma concentrations greater than 3.5 mg/dL may result in toxicity. Doses of 2000 to 2500 international units/day or more can produce gastrointestinal distress. In a meta-analysis, mortality (from all causes) may increase at doses of greater than 400 International Units/day (greater than 400 mg/day). Daily intake of 200 to 600 mg of vitamin E is innocuous in most people; however, long-term use of doses over 400 units/day has caused diarrhea, nausea, flatulence, or stomach cramps in some patients.
    B) THERAPEUTIC DOSE: RECOMMENDED DIETARY ALLOWANCES: 0 to 6 months: 6 (4 mg) International Units/day; 7 to 12 months: 7.5 (5 mg) International Units/day; 1 to 3 years: 9 (6 mg) International Units/day; 4 to 8 years: 10.4 (7 mg) International Units/day; 9 to 13 years: 16.4 (11 mg) International Units/day and 14 years and older: 22.4 (15 mg) International Units/day.
    C) TOCOFERSOLAN: PEDIATRIC: Recommended daily dose in patients with congenital or hereditary chronic cholestasis is 0.34 mL/kg/day (or 17 mg/kg/day of d-alpha-tocopherol in the form of tocofersolan).

Therapeutic Dose

    7.2.1) ADULT
    A) RECOMMENDED DAILY ALLOWANCE
    1) Food and Nutrition Board of National Research Council recommendation: 15 international units (10 milligrams of d-alpha-tocopherol)/day for adult men and 12 international units (8 milligrams of d-alpha-tocopherol)/day for adult women (HSDB , 2001).
    2) The recommended daily dietary allowance (RDA):
    a) FEMALES 11 YEARS OF AGE AND OLDER: 12 International Units (8 mg of alpha-tocopherol equivalents) (HSDB , 2001).
    b) MALES 11 YEARS OF AGE AND OLDER: 15 International Units (10 mg of alpha-tocopherol equivalents) (HSDB , 2001).
    c) PREGNANT WOMEN: 15 International Units (10 mg of alpha-tocopherol equivalents) (HSDB , 2001).
    d) LACTATING WOMEN: 16 to 18 International Units (11 to 12 mg of alpha-tocopherol equivalents) (HSDB , 2001).
    7.2.2) PEDIATRIC
    A) RECOMMENDED DIETARY ALLOWANCE
    1) The recommended daily dietary allowance (RDA):
    a) INFANTS UP TO 6 MONTHS OF AGE AND 6 to 12 MONTHS OF AGE: 5 and 6 International Units (3 and 4 mg of alpha-tocopherol equivalents), respectively (HSDB , 2001).
    b) CHILDREN 1 to 3 AND 4 to 10 YEARS OF AGE: 9 and 11 International Units (6 and 7 mg of alpha-tocopherol equivalents), respectively (HSDB , 2001).
    B) TOCOFERSOLAN
    1) CONGENITAL OR HEREDITARY CHRONIC CHOLESTASIS: Recommended total daily dose is 0.34 mL/kg/day (or 17 mg/kg/day of d-alpha-toceopherol in the form of tocofersolan) in pediatric patients with congenital chronic or hereditary cholestasis. Dose adjustment is based on plasma vitamin E concentration (Prod Info Vedrop oral solution, 2012).

Maximum Tolerated Exposure

    A) SUMMARY
    1) One study suggests that a daily dosage of 100 to 300 mg is considered harmless from a toxicological standpoint (HSDB , 2001). Daily intake of 200 to 600 mg vitamin E is innocuous in most people (Bieri et al, 1983); however, long-term use of doses over 400 units/day has caused diarrhea, nausea, flatulence, or stomach cramps in some patients (HSDB , 2001).
    2) Vitamin E plasma concentrations greater than 3.5 mg/dL may result in toxicity. In several animal species, the estimated oral median dose is 2000 mg/kg (2000 International Units/kg). In a meta-analysis, mortality (from all causes) may increase at doses of greater than 400 International Units/day (greater than 400 mg/day) (Ginsburg, 2011).
    3) Doses of 2000 to 2500 International Units/day (2000 to 2500 mg/day) can produce nausea and gastric distress. Patients receiving doses of 3200 International Units/day reported diarrhea and abdominal cramps. Doses of 1000 International Units/day (1000 mg/day) have been shown to antagonize the effects of vitamin K by increasing the epoxidation of vitamin K to its inactive form. Although not likely to occur in healthy individuals, a coagulopathy may develop in patients receiving warfarin or having a history of vitamin K deficiency (Ginsburg, 2011).
    4) TOLERABLE UPPER INTAKE LEVELS: PEDIATRIC: 1 to 3 years: 300 (200 mg) International Units/day; 4 to 8 years: 450 (300 mg) International Units/day; 9 to 13 years: 900 (600 mg) International Units/day; 14 to 18 years: 1200 (800 mg) International Units/day; ADULT: 19 years of age and older: 1500 (1000 mg) International Units/day (Office of Dietary Supplements, 2011).

Serum Plasma Blood Concentrations

    7.5.1) THERAPEUTIC CONCENTRATIONS
    A) THERAPEUTIC CONCENTRATION LEVELS
    1) CONCENTRATION LEVEL
    a) Healthy adult: 0.5 to 2.5 mg/dL (Lemons & Maisels, 1985).
    b) Premature infant: 1 to 2 mg/dL (Amorde-Spalding et al, 1992).
    1) The American Academy of Pediatrics recommends 1 to 2 mg/dL for infants less than 1500 g (Amorde-Spalding et al, 1992).
    c) Immunostimulation: 2.1 mg/dL (Meydani et al, 1997).
    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CONCENTRATION LEVEL
    a) Vitamin E plasma concentrations greater than 3.5 mg/dL may result in toxicity (Lemons & Maisels, 1985; Bieri et al, 1983). Prolonged vitamin E plasma levels of approximately 4.5 mg/dL were associated with an increased incidence of bacterial sepsis and necrotizing enterocolitis (Johnson et al, 1985).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Vitamin E is a lipo-soluble antioxidant that acts as a free radical chain breaking molecule within membranes to prevent propagated oxidation of unsaturated fatty acids (Prod Info Vedrop oral solution, 2012; Spielberg et al, 1979). It is also involved in maintaining the stability and integrity of cell membranes (Prod Info Vedrop oral solution, 2012).
    B) Vitamin E is hypothesized to reduce atherosclerosis and subsequent coronary heart disease by preventing oxidative changes to low-density lipoproteins (LDL). Oxidized LDL particles are more readily converted by macrophages than native LDL to the cholesterol-loaded foam cells found in the fatty streak of early atherosclerosis. Atherogenesis may also be promoted by oxidized LDL's chemotactic action on monocytes, its cytotoxicity to endothelial cells, its stimulation of the release of growth factors and cytokines, its immunogenicity, and its possible arterial vasoconstrictor actions (Rimm et al, 1993; Stampfer et al, 1993).

Physicochemical

Physical Characteristics

    A) Vitamin E is a pale yellow viscous oil with little or no odor, and little or no taste (HSDB , 2001).

Molecular Weight

    A) 430.69 (HSDB , 2001)

References

General Bibliography

    1) Amorde-Spalding K, D'Harlingue AE, & Phillips BL: Tocopherol levels in infants less than or equal to 1000 grams receiving MVI pediatric. Exp Reason 1992; 90(suppl 6):992-994.
    2) Bazzano C, de Angeles S, & Kleist G: Allergic contact dermatitis from topical vitamins A and E. Contact Dermatitis 1996; 35(4):261-262.
    3) Bieri JG, Corash L, & Hubbard VS: Medical uses of vitamin E. N Engl J Med 1983; 308(18):1063-1071.
    4) Briggs GG, Freeman RK, & Yaffe SJ: Drugs in Pregnancy and Lactation, 5th ed, Williams and Wilkins, Baltimore, MD, 1998.
    5) Danielle L, Foley DJ, Masaki KH, et al: Vitamin E and C supplements and risk of dementia.. JAMA 2002; 288(18):2266-2268.
    6) Farrell PM & Roberts RJ: Vitamin E, in Shils ME, Olsen JA & Shike M (eds): Modern Nutrition in Health and Disease, 8th ed, Lea & Febiger, Philadelphia, PA, 1994, pp 326-341.
    7) Gilman AG, Goodman LS, & Rall TW: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, Macmillan Publishing Co, New York, NY, 1990.
    8) Ginsburg BY: Vitamins. In: Nelson LS, Lewin LA, Howland MA, et al, eds. Goldfrank’s Toxicologic Emergencies, McGraw Hill, New York, NY, 2011, pp 609-623.
    9) Goldman MP & Rapaport M: Contact dermatitis to vitamin E oil (letter). J Am Acad Dermatol 1986; 14(1):133-134.
    10) HSDB : Hazardous Substances Data Bank. National Library of Medicine. Bethesda, MD (Internet Version). Edition expires 2001; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    11) Hunter D & Frumkin A: Adverse reactions to vitamin E and aloe vera preparations after dermabrasion and chemical peel. Cutis 1991; 47(3):193-196.
    12) Jellin JM, Gregory P, & Batz F: Pharmacist's letter/Prescriber's Letter Natural Medicines Comprehensive Database, 3rd ed, Therapeutic Research Faculty, Stockton, CA, 2000.
    13) Johnson L, Bowen FW Jr, & Abbasi S: Relationship of prolonged pharmacologic serum levels of vitamin E to incidence of sepsis and necrotizing enterocolitis in infants with birth weight 1500 grams or less. Pediatrics 1985; 75:619-638.
    14) Lemons JA & Maisels MJ: Vitamin E-how much is too much?. Pediatrics 1985; 76:625-627.
    15) Liede KE, Haukka JK, & Saxen LM: Increased tendency towards gingival bleeding caused by joint effect of alpha-tocopherol supplementation and acetylsalicylic acid. Ann Med 1998; 30:542-546.
    16) Meydani SN, Meydani M, & Blumberg JB: Vitamin E supplementation and in vivo immune response in healthy elderly subjects: a randomized controlled trial. JAMA 1997; 277:1380-1386.
    17) Meyers DG, Maloley PA, & Weeks D: Safety of antioxidant vitamins. Arch Intern Med 1996; 156(9):925-935.
    18) Office of Dietary Supplements: Dietary Supplement Ingredient Database. National Institutes of Health. Bethesda, MD. 2013. Available from URL: http://dietarysupplementdatabase.usda.nih.gov/research_summary.html. As accessed 2014-07-23.
    19) Office of Dietary Supplements: Dietary Supplements Fact Sheet: Vitamin E. National Institutes of Health. Bethesda, MD. 2011. Available from URL: http://ods.od.nih.gov/factsheets/vitamine. As accessed 2011-12-22.
    20) Phelps DL, Rosenbaum AL, & Isenberg SJ: Tocopherol efficacy and safety for preventing retinopathy of prematurity: a randomized, controlled, double-masked trial. Pediatrics 1987; 79(4):489-500.
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    22) Product Information: Vedrop oral solution, tocofersolan oral solution. Orphan Europe S.A.R.L. (per EMA), Puteaux, France, 2012.
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