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Drugs and Health Products

Monograph: Beta-Carotene

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This monograph is intended to serve as a guide to industry for the preparation of Product Licence Applications (PLA) 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. Notes: (i) Text in parentheses is additional optional information which can be included on the PLA and product label at the applicant's 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) Consult Appendix 1 for definitions of the following terms: Adequate Intake (AI), Recommended Dietary Allowance (RDA), Tolerable Upper Intake Level (UL).

Date: 2010-06-11

NHPID Name

Beta-carotene (O'Neil et al. 2012)

Proper Name(s)

Common Name(s)

Source Material

All-trans-beta-carotene (Sweetman 2007, IOM 2003)
The slash indicates that the terms are synonyms. Either term may be selected by the applicant.

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
  • Source of vitamin A for the maintenance of good health  (IOM 2006)
  • Provitamin A for the maintenance of good health.  (IOM 2006)


Specific

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

Dose(s)

Children 0 - 3 years:

Dose(s): 180 - 3600 Micrograms per day

Children 4 - 8 years:

Dose(s): 180 - 5400 Micrograms per day

Adolescents 9 - 13 years:

Dose(s): 180 - 10200 Micrograms per day

Adolescents 14 - 18 years:

Dose(s): 390 - 16800 Micrograms per day

Adults:

Dose(s): 390 - 18000 Micrograms per day

  • Adults includes pregnant and breastfeeding women.
  • Beta-carotene doses were derived from the conversion factor of 6 g of beta-carotene = 1 g all-trans retinol; hence, a ratio of 6:1 beta-carotene:vitamin A, on a weight to weight basis (HC 1990; FAO/WHO 1967).
  • International Units (IU) may be provided as optional additional information on the PLA form, using the following USP conversion factor: 1 IU of beta-carotene = 0.6 g of all-trans beta-carotene.
  • The daily minimum doses are based on approximately 5% of the highest RDA or AI for vitamin A(IOM 2006). See Appendix 1 for definitions and Table 3 in Appendix 2 for RDA values and AI values
  • The maximum daily dose is based on the Tolerable Upper Intake Level (UL) for vitamin A, which applies to total vitamin A intake from food and supplements (IOM 2006).

Duration of use

No statement is required

Risk Information

Statement(s) to the effect of:

Caution(s) and Warning(s):
Doses greater than or equal to 6001 Micrograms per day:
Consult a health care practitioner prior to use if you are a tobacco smoker  (Touvier et al. 2005, Omenn et al. 1996, ATBC Study Group 1994)

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 Beta Carotene and Beta Carotene Capsules monographs published in the U.S. Pharmacopeia (USP 32), and the Betacarotene monographs published in the European Pharmacopoeia (Ph. Eur. 2008) and the British Pharmacopoeia (BP 2008).

References cited

  • ATBC (Alpha-tocopherol, beta-carotene cancer prevention) study group. 1994. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The New England Journal of Medicine 330(15):1029-1035.
  • BP 2009: British Pharmacopoeia Commission. 2009. British Pharmacopoeia, 2009, Volume 1. London (GB): The Stationary Office on behalf of the Medicines and Healthcare products Regulatory Agency (MHRA).
  • European Pharmacopoeia, 6th edition. Strasbourg (France): Directorate for the Quality of Medicines and HealthCare of the Council of Europe (EDQM).; 2008
  • FAO/WHO 1967: Food and Agricultural Organization of the United Nations / World Health Organization. 1967. Requirements of vitamin A, thiamine, riboflavine and niacin: report of a joint FAO/WHO Expert Group. Geneva: WHO Technical Report Series 362.
  • Groff J, Gropper S. Advanced Nutrition and Human Metabolism, 3rd edition. Belmont (CA): Wadsworth/Thomson Learning; 2000.
  • HC 1990: Health Canada. 1990. Nutrition Recommendations. The Report of the Scientific Review Committee. Ottawa: Minister of Supply and Services.
  • IOM 2003: Institute of Medicine. Committee on Food Chemicals Codex, Food and Nutrition Board, Institute of Medicine. Food Chemicals Codex, 5th edition. Washington (DC): National Academies Press; 2003.
  • IOM 2006: Institute of Medicine. Otten JJ, Pitzi Hellwig J, Meyers LD, editors. Institute of Medicine. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington (DC): National Academies Press; 2006.
  • O'Neil MJ, Heckelman PE, Koch CB, Roman KJ, editors. 2009. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals [en ligne]. Whitehouse Station (NJ): Merck & Co., Inc. Electronic version [Accessed February 4, 2010]. Available from : http://www.medicinescomplete.com
  • Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, Keogh JP, Meyskens FL, Valanis B, Williams JH, Barnhart S, Hammar S. 1996. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. New England Journal of Medicine 334(18):1150-1155.
  • Shils ME, Olson JA, Shike M, Ross AC, Caballero B, Cousins RJ, editors. Modern Nutrition in Health and Disease, 10th edition. Philadelphia (PA): Lippincott Williams & Wilkins; 2006.
  • Sweetman SC , editor. Martindale: The Complete Drug Reference, 35th edition. London (UK): Pharmaceutical Press; 2007.
  • Touvier M, Kess E, Clavel-Chapelon F, and Boutron-Rualt MC. 2005. Dual association of beta-carotene with risk of tobacco-related cancers in a cohort of French women. Journal of the National Cancer Institute 97(18):1338-1344.
  • USP 32 : United States Pharmacopeial Convention. 2009. United States Pharmacopeia and the National Formulary (USP 32 - NF 27). Rockville (MD): The United States Pharmacopeial Convention.

References reviewed

  • Burri BJ, Clifford AJ. 2004. Carotenoid and retinoid metabolism: insights from isotope studies. Archives of Biochemistry and Biophysics 430:110-119.
  • Dueker SR, Lin Y, Buchholz BA, Schneider PD, Lam MW, Segall HJ, Vogel JS, Clifford AJ. 2000. Long-term kinetic study of -carotene, using acceleratory mass spectrometry in an adult volunteer. Journal of Lipid Research 41:1790-1800.
  • Expert Group on Vitamins and Minerals. 2003. Safe Upper Levels for Vitamins and Minerals. United Kingdom Food Standards Agency. [online]. [Accessed 2010 January 27]. Available from: http://cot.food.gov.uk/pdfs/vitmin2003.pdf
  • Furr HC, Green MH, Haskell M, Mokhtar N, Nestel P, Newton S, Ribaya-Mercado JD, Tang G, Tanumihardjo S, Wasantwisut E. 2005. Stable isotope dilution techniques for assessing vitamin A status and bioefficacy of provitamin A carotenoids in humans. Public Health Nutrition 8(6):596-607.
  • Haskell MJ, Brown KH. 2005. Reply to M van Lieshout and S de Pee. American Journal of Clinical Nutrition 81(4):945-946.
  • HC 1995: Health Canada 1995. Drugs Directorate Labelling Standard: Vitamin Supplements.
  • HC 1996: Health Canada. Drugs Directorate Labelling Standard: Mineral Supplements. Ottawa (ON): Health Canada.
  • HC 2007: Health Canada. Monograph- Multi-vitamin/mineral Supplement. [Accessed 2009 December 4]. Available from: http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/prodnatur/multivit_min_mono-eng.pdf
  • Hickenbottom SJ, Follett JR, Lin Y, Dueker SR, Burri BJ, Neidlinger TR, Clifford AJ. 2002. Variability in conversion of -carotene to vitamin A in men as measured by using a double-tracer study design. American Journal of Clinical Nutrition 75:900-907.
  • Hickenbottom SJ, Lemke SL, Dueker SR, Lin Y, Follett JR, Carkeet C, Buchholz BA, Vogel JS, Clifford AJ. 2002. Dual isotope test for assessing -carotene cleavage to vitamin A in humans. European Journal of Nutrition 41:141-147.
  • IOM 2001: Institute of Medicine. Panel on Micronutrients, Subcommittees on Upper Reference Levels of Nutrients and Interpretation and Uses of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington (DC): National Academy Press; 2001.
  • JC 2008: Justice Canada. Food and Drug Regulations. (C.01.021). Ottawa (ON): Health Canada; 2008. [Accessed 2008-01-31] Available from: http://laws.justice.gc.ca/en/F-27/C.R.C.-c.870/text.html
  • JC 2012: Justice Canada. Natural Health Products Regulations [Internet]. Ottawa (ON): Justice Canada. Available from: http://laws-lois.justice.gc.ca/eng/regulations/SOR-2003-196/index.html [Current 2012 December 31, Last amended 2008-06-01; Accessed 2013 January 30].
  • Lemke SL, Dueker SR, Follett JR, Lin Y, Carkeet C, Buchholz BA, Vogel JS, Clifford AJ. 2003. Absorption and retinol equivalence of -carotene in humans is influenced by dietary vitamin A intake. Journal of Lipid Research 44:1591-1600.
  • Lin Y, Dueker SR, Burri BJ, Neidlinger TR, Clifford AJ. 2000. Variability of the conversion of -carotene to vitamin A in women measured by using a double-tracer study design. American Journal of Clinical Nutrition 71:1545-1554.
  • Ribaya-Mercado JD, Solon FS, Solon MA, Cabal-Barza MA, Perfecto CS, Tang G, Solon JAA, Fjeld CR, Russell RM. 2000. Bioconversion of plant carotenoids to vitamin A in Filipino school-aged children varies inversely with vitamin A status. American Journal of Clinical Nutrition 72:455-465.
  • Russell RM, Ross AC, Trumbo PR, West KP. 2003. Retinol equivalency ratio of -carotene. Journal of Nutrition 133:2915.
  • Tang G, Qin J, Dolnikowski GG, Russell RM. 2000. Vitamin A equivalence of -carotene in a woman as determined by a stable isotope reference method. European Journal of Nutrition 39:7-11.
  • Tang G, Qin J, Dolnikowski GG, Russell RM. 2003. Short-term (intestinal) and long-term (postintestinal) conversion of -carotene to retinol in adults as assessed by a stable-isotope reference method. American Journal of Clinical Nutrition 78:259-266.
  • van Lieshout M, de Pee S. 2005. Vitamin A equivalency estimates: understanding apparent differences. American Journal of Clinical Nutrition 81(4):943-945.
  • van Lieshout M, West CE, Muhilal, Permaesih D, Wang Y, Xu X, van Breemen RB, Creemers AFL, Verhoeven MA, Lugtenburg J. 2001. Bioefficacy of -carotene dissolved in oil studied in children in Indonesia. American Journal of Clinical Nutrition 73:949-958.
  • Van Loo-Bouwman CA, West CE, van Breeman RB, Zhu D, Siebelink E, Versloot P, Hulshof PJM, van Lieshout M, Russel FGM, Schaafsma G, Naber THJ. 2009. Vitamin A equivalency of -carotene in healthy adults: limitations of the extrinsic dual-isotope dilution technique to measure matrix effect. British Journal of Nutrition 101:1837-1845.
  • Wang Z, Yin S, Zhao X, Russell RM, Tang G. 2004. -Carotene - vitamin A equivalence in Chinese adults assessed by an isotope dilution technique. British Journal of Nutrition 91:121-131.
  • West CE, Eilander A, van Lieshout M. 2002. Consequences of revised estimates of carotenoid bioefficacy for dietary control of vitamin A deficiency in developing countries. Journal of Nutrition 132:2920S-2926S.
  • West CE, Eilander A, van Lieshout M. 2003. Reply to Russel et al. Journal of Nutrition 133:2917.
  • WHO/FAO 2004: World Health Organization / Food and Agricultural Organization of the United Nations. 2004. Vitamin and mineral requirements in human nutrition, 2nd edition. [online]. [Accessed 2010 January 27]. Available from: http://www.who.int/nutrition/publications/micronutrients/9241546123/en/

Appendix 1: Definitions

Adequate Intake (AI):

The recommended average daily intake level based on observed or experimentally determined approximations or estimates of nutrient intake by a group (or groups) of apparently healthy people that are assumed to be adequate. An AI is used when a Recommended Dietary Allowance (RDA) cannot be determined (IOM 2006).

Recommended Dietary Allowance (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).

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).

 

Appendix 2: Dose information for Vitamin A deficiency use or purpose

Table 1: Dose information for Vitamin A deficiency for beta-carotene
Life stage group beta-carotene (g/day) Footnote 1

Footnotes

Footnote 1

The AI is indicated by an asterisk.

Return to Table 1 footnote 1 referrer

Infants 0-6 mo 2400*
7-12 mo 3000*
Children 1-3 y 1800
4-8 y 2400
Adolescent males 9-13 y 3600
14-18 y 5400
Adolescent females 9-13 y 3600
14-18 y 4200
Adult males > 18 y 5400
Adult females > 18 y 4200
Pregnancy 14-18 y 4250
19-50 y 4270
Breastfeeding 14-18 y 7200
19-50 y 7800

The beta-carotene values were derived from the conversion factor of 6 g of beta-carotene carotene = 1 g all-trans retinol; hence, a ratio of 6:1 beta-carotene:vitamin A, on a weight to weight basis (HC 1990; FAO/WHO 1967). They are based on RDA and AI values for Vitamin A based on life stage group (IOM 2006).