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Drugs and Health Products

Monograph: Vitamin E (from rac-alpha-tocopherol and esters)

This monograph is intended to serve as a guide to industry for the preparation of Product Licence Applications and labels for natural health product market authorization. It is not intended to be a comprehensive review of the medicinal ingredient. It is a referenced document to be used as a labelling standard. Note: (i) Text in parentheses is additional optional information which can be included on the Product Licence Application and product labels at the applicants' discretion. The solidus (/) indicates that the terms are synonyms or that the statements are synonymous. Either term or statement may be selected by the applicant. (ii) This monograph is only applicable when the source of Vitamin E is rac-alpha-tocopherol and its esters. When RRR-alpha-tocopherol and its esters are the source of Vitamin E, please refer to the monograph named 'Vitamin E (from RRR-alpha-tocopherol and its esters)'.

Date: 2009-06-18

NHPID Name

Vitamin E (O'Neil et al. 2012)

Proper Name(s)

Vitamin E ( USP 2009 , IOM 2006 )

Common Name(s)

Vitamin E ( USP 2009 , IOM 2006 )

Source Material


Route Of Administration

Oral

Dosage Form(s)

  • The acceptable pharmaceutical dosage forms include, but are not limited to capsules, chewables (e.g. gummies, tablets), liquids, powders, strips or tablets.
  • This monograph is not intended to include foods or food-like dosage forms such as bars, chewing gums or beverages.

Use(s) or Purpose(s)

Statement(s) to the effect of:

General
A factor in the maintenance of good health  (IOM 2006)

Specific
An antioxidant for the maintenance of good health  (IOM 2006, Shils et al. 2006, Groff and Gropper 2000)

Dose-specific
For products providing daily doses of Vitamin E at or above the Recommended Dietary Allowance (RDA):
Helps to prevent vitamin E deficiency  (IOM 2006, Shils et al. 2006, Groff and Gropper 2000)

Dose(s)

Children 1 - 3 years:

Dose(s): 0.6 - 100 Milligrams Alpha-Tocopherol per day

Children 4 - 8 years:

Dose(s): 0.6 - 150 Milligrams Alpha-Tocopherol per day

Adolescents 9 - 13 years:

Dose(s): 0.6 - 300 Milligrams Alpha-Tocopherol per day

Adolescents 14 - 18 years:

Dose(s): 1 - 400 Milligrams Alpha-Tocopherol per day

Adults:

Dose(s): 1 - 500 Milligrams Alpha-Tocopherol per day

  • Adults includes pregnant and breastfeeding women.
  • The daily minimum doses are based on approximately 5% of the highest RDA (IOM 2006). See Appendix 1 for definitions and Table 1 in Appendix 2 for RDA values.
  • The maximum values are based on the Tolerable Upper Intake Level (UL) which applies to vitamin E intake from supplements only (IOM 2006). These values have been modified for regulatory purposes. See Appendix 1 for more information.
  • Vitamin E deficiency is rare in North America (IOM 2006; Shils et al. 2006; Groff and Gropper 2000).
  • Vitamin E must be expressed as milligrams (mg) of 2R alpha- tocopherol (AT) irrespective of the source material used. See Appendix 1 for an explanation of this definition. For all rac-alpha-tocopherol and its esters (i.e. all rac-alpha-tocopherol, all rac-alpha-tocopheryl acetate, all rac-alpha-tocopheryl succinate): (i) 1 mg of All rac-alpha-tocopherol = 0.50 mg AT of Vitamin E = 1.10 IU, (ii) 1 mg of All rac-alpha-tocopheryl acetate = 0.45 mg AT of Vitamin E = 1.00 IU, (iii) 1 mg of All rac-alpha-tocopheryl succinate = 0.41 mg AT of Vitamin E = 0.89 IU. (1 IU of all rac-alpha-tocopherol and its esters = 0.45 mg AT of Vitamin E).

Duration of use

No statement is required

Risk Information

Statement(s) to the effect of:

Caution(s) and Warning(s):

Contraindication(s):
No statement is required

Known Adverse Reaction(s):
No statement is required

Non-medicinal ingredients

Must be chosen from the current Natural Health Products Ingredients Database and must meet the limitations outlined in the database.

Specifications

  • The finished product specifications must be established in accordance with the requirements described in the NHPD Quality of Natural Health Products Guide.
  • The medicinal ingredient must comply with the requirements outlined in the Natural Health Products Ingredient Database (NHPID).
  • The medicinal ingredient may comply with the specifications outlined in the following pharmacopoeial monographs: 'All-rac-alpha-Tocopherol', 'All-rac-alpha-Tocopheryl Acetate', and 'DL-alpha-Tocopheryl Hydrogen Succinate' from the European Pharmacopoeia (Ph. Eur.) or 'Vitamin E', 'Vitamin E Preparation' and 'Vitamin E Capsules' from the US Pharmacopoeia (USP).

References cited

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  • Groff J, Gropper S. Advanced Nutrition and Human Metabolism, 3rd edition. Belmont (CA): Wadsworth/Thomson Learning; 2000.
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  • Meyer F, Bairati I, Fortin A, Gélinas M, Nabid A, Brochet F, Têtu B. 2008. Interaction between antioxidant vitamin supplementation and cigarette smoking during radiation therapy in relation to long-term effects on recurrence and mortality: A randomized trial among head and neck cancer patients. International Journal of Cancer 122(7):1679-1683.
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  • Winterbone MS, Sampson MJ, Saha S, Hughes JC, Hughes DA. 2007. Pro-oxidant effect of alpha-tocopherol in patients with type 2 diabetes after an oral glucose tolerance test-a randomised controlled trial. Cardiovascular Diabetology 6:8.

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Appendix 1: Definitions

2R-Alpha-tocopherol:

The only forms of α-tocopherol that are maintained in plasma are RRR-α-tocopherol, the form of  α-tocopherol that occurs naturally in foods, and the 2R-stereoisomeric forms of α-tocopherol (i.e. RRR-, RSR-, RRS-, and RSS- α-tocopherol) present in synthetic all rac­- α-tocopherol. Since the 2S-stereoisomers of α-tocopherol, part of the synthetic all rac­- α-tocopherol, are not maintained in human plasma or tissues they are not included in the definition of active components of vitamin E for humans.

 

Recommended Dietary Allowances (RDA):

  • The average daily dietary nutrient intake level sufficient to meet the nutrient requirements of nearly all (97-98 %) healthy individuals in a particular life stage and gender group (IOM 2006).
  • For the purpose of establishing the RDA, the IOM defined vitamin E activity as being limited to the 2R-stereoisomeric forms of α-tocopherol. This is because the 2R forms are the only ones that are maintained in the plasma (IOM 2006).

Tolerable Upper Intake Level (UL):

  • The highest average daily nutrient intake level that is likely to pose no risk of adverse health effects to almost all individuals in the general population. As intake increases above the UL, the potential risk of adverse effects may increase (IOM 2006).
  • For the purpose of establishing the UL, the IOM considered all eight stereoisomeric forms of supplemental α-tocopherol (2R and 2S). This is because all eight forms are absorbed and can thus potentially contribute to vitamin E toxicity (IOM 2006).

 

Note: The minimum dosage limits outlined above were derived as approximately 5% of the RDA, a value which takes into account the 2R stereoisomers only (i.e. four of the eight stereoisomers). The maximum dosage limits were modeled after the UL, a value which takes into account all eight stereoisomers. RRR-α-tocopherol and its esters contain only 2R stereoisomeric forms, whereas all rac-α-tocopherol and its esters contain both 2R and 2S stereoisomeric forms (i.e. all eight stereoisomers). To reconcile these differences, the maximum dosage limits for all racemic-α-tocopherol sources were divided in half.

 

 

Appendix 2: RDA Values

The RDA values for vitamin E are provided below. For the purpose of this monograph, these values are intended to:

  • provide target values for setting appropriate supplement dosage levels;
  • provide the minimum dose for the use of the dose-specific use or purpose: "Helps to prevent vitamin E deficiency";
  • facilitate the optional labelling of % RDA values

Table 1: Recommended Dietary Allowance values for vitamin E based on life stage group (IOM 2006)
Life stage group Vitamin E (mg AT/day)
Children 1-3 y 6
4-8 y 7
Adolescents 9-13 y 11
14-18 y 15
Adults ≥19 15
Pregnancy 14-50 y 15
Breastfeeding 14-50 y 19

Appendix 3: Examples using the vitamin E conversion factors:

a. Converting vitamin E source material quantity into quantity of AT (mg)

Convert 200 mg of all rac-α-tocopheryl acetate into mg AT:

= 200 mg x 0.45 mg AT/mg

= 90 mg AT

 

b. Converting vitamin E activity into quantity of AT (mg)

Convert 400 IU of all rac- α -tocopherol into mg AT:

= 400 IU x 0.45 mg AT/IU

= 180 mg AT