Beta-carotene (Systemic)


VA CLASSIFICATION
Primary: VT050
Secondary: DE890

Commonly used brand name(s): Lumitene; Max-Caro.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Nutritional supplement (vitamin precursor)—

photosensitivity reaction suppressant in erythropoietic protoporphyria—

polymorphous light eruption suppressant—
Note: Beta-carotene is a precursor to vitamin A (a fat-soluble vitamin).



Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Vitamin A deficiency (prophylaxis){12}{13}{14}—Beta-carotene may be used for prevention of vitamin A deficiency states in most individuals. Vitamin A deficiency may occur as a result of inadequate nutrition or intestinal malabsorption but does not occur in healthy individuals receiving an adequate balanced diet. For prophylaxis of vitamin A deficiency, dietary improvement, rather than supplementation, is advisable. For treatment of vitamin A deficiency, supplementation with vitamin A is preferred. {48}
—Deficiency of vitamin A may lead to keratomalacia, xerophthalmia, and nyctalopia (night blindness). {19}
—Recommended intakes may be increased and/or supplementation may be necessary in the following conditions (based on documented vitamin A deficiency):

• Fat malabsorption (steatorrhea) {01}


• Fever, chronic


• Hepatic-biliary tract disease—hepatic function impairment, cirrhosis, obstructive jaundice {18}


• Infection, prolonged


• Malabsorption syndromes associated with pancreatic insufficiency—pancreatic disease, cystic fibrosis {18}


• Protein deficiency, severe

—Some unusual diets (e.g., reducing diets that drastically restrict food selection) may not supply minimum daily requirements of vitamin A. Supplementation is necessary in patients receiving total parenteral nutrition (TPN) or undergoing rapid weight loss or in those with malnutrition, because of inadequate dietary intake.
—Recommended intakes for most vitamins and minerals are increased during pregnancy. Many physicians recommend that pregnant women receive multivitamin and mineral supplements, especially those pregnant women who do not consume an adequate diet and those in high-risk categories (i.e., women carrying more than one fetus, heavy cigarette smokers, and alcohol and drug abusers). {31} Taking excessive amounts of a multivitamin and mineral supplement may be harmful to the mother and/or fetus and should be avoided.
—Recommended intakes for most vitamins and minerals are increased during breast-feeding.
—Recommended intakes of vitamin A may be increased by the following medications: Cholestyramine, colestipol, mineral oil, and neomycin {05} {06} {07} {08} {09} {10}.

[Photosensitivity reactions in erythropoietic protoporphyria (prophylaxis and treatment)]1—Beta-carotene is indicated to reduce the severity of photosensitivity reactions in patients with erythropoietic protoporphyria (EPP). {02} {33} {50}

[Polymorphous light eruption (prophylaxis and treatment)]1—Beta-carotene is used in the prophylaxis and treatment of severe cases of polymorphous light eruption. {03} {04} {11}

Acceptance not established
Although it has been documented that individuals who consume foods containing high levels of beta-carotene have a reduced risk of certain types of cancer and possibly cardiovascular disease {49}, there are insufficient data to show the same relationship using beta-carotene supplements {12} {38}. Use cannot be recommended in individuals with a history of smoking and/or asbestos exposure, since two large trials have found an increased incidence of lung cancer when beta-carotene supplements were given to these populations {13} {14}. However, another large trial using beta-carotene supplements found no increased risk of lung cancer {12}. Research is underway to determine whether beta-carotene may have raised cancer risks only in subpopulations (e.g., smokers, drinkers of alcohol) {51} {55}. It is also possible that some formulations of beta-carotene may not raise beta-carotene concentrations as much as the preparations used in these two studies {12} {51}.

Unaccepted
Beta-carotene has not been proven effective as a sunscreen. {01}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Mechanism of action/Effect:

Nutritional supplement—Beta-carotene is a precursor to vitamin A, which is essential for normal function of the retina; in the form of retinal, it combines with opsin (red pigment in the retina) to form rhodopsin (visual purple), which is necessary for visual adaptation to darkness. {17} It is also necessary for growth of bone, testicular and ovarian function, and embryonic development, and for regulation of growth and differentiation of epithelial tissues. {18}

Photosensitivity reaction—Beta-carotene quenches singlet oxygen and free radicals that are generated when porphyrin is exposed to light and air. {34} {35}

Absorption:

Absorption of beta-carotene depends on the presence of dietary fat and bile in the intestinal tract. {01} {15} {16}


Storage

Unchanged beta-carotene is found in various tissues, primarily fat tissues, adrenal glands, and ovaries. {01} {17} {56} {57} Small concentrations are found in the liver. {17}

Biotransformation:

Approximately 20 to 60% of beta-carotene is metabolized to retinaldehyde and then converted to retinol, {01} {17} {30} primarily in the intestinal wall. A small amount of beta-carotene is converted to vitamin A in the liver. {01} The proportion of beta-carotene converted to vitamin A diminishes inversely to the intake of beta-carotene, as long as the dosages are higher than one to two times the daily requirements. {20} High doses of beta-carotene do not lead to abnormally high serum concentrations of vitamin A.

Elimination:
    Primarily fecal. {01}


Precautions to Consider

Carcinogenicity

Two large studies have found an increased incidence in lung cancers when beta-carotene supplements were given to individuals with a history of smoking and/or asbestos exposure. One study of 29,000 males with a history of smoking found an 18% increase in the incidence of lung cancer in the group receiving 20 mg of beta-carotene a day for 5 to 8 years as compared with those receiving placebo {13}. Another study of 18,000 individuals found 28% more lung cancers in individuals with a history of smoking and/or asbestos exposure who took 30 mg of beta-carotene in addition to 25,000 Units of retinol a day for 4 years as compared with those receiving placebo {14}. However, one study of 22,000 male physicians, some of them smokers and former smokers, found no increased risk of lung cancer at doses of 50 mg of beta-carotene every other day for 12 years {12}.

Mutagenicity

In vitro and in vivo mutagenicity studies were negative. {01}

Pregnancy/Reproduction
Fertility—
No problems with fertility have been documented in women taking up to 30 mg (5000 retinol equivalents [RE]) of beta-carotene a day. The effects of doses greater than 30 mg a day are not known. {48}

Beta-carotene did not affect fertility in male rats at doses of up to 100 times the recommended human dose. {01}

Pregnancy—
Beta-carotene crosses the placenta. Adequate and well-controlled studies in humans have not been done. However, no problems with pregnancy have been documented in women taking up to 30 mg (5000 RE) of beta-carotene a day. The effects of doses greater than 30 mg (5000 RE) a day are not known. {48}

Studies in rats at doses 300 to 400 times the recommended human dose have shown that beta-carotene causes an increase in resorption rate. No increase in resorption rate was noted in rats receiving 75 times the recommended human dose or less. {01}

FDA Pregnancy Category C. {01}

Breast-feeding

Problems in humans have not been documented with intake of normal daily recommended amounts.

Pediatrics

Problems in pediatrics have not been documented with intake of normal daily recommended amounts.


Geriatrics


Problems in geriatrics have not been documented with intake of normal daily recommended amounts.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following, depending on the amount present, may also interact with beta-carotene.

Asbestos exposure, or history of or{14}
Smoking tobacco, or history of{13}{14}    (data from two large studies indicate an increased incidence of lung cancers when beta-carotene supplements were given to individuals with a history of smoking and/or asbestos exposure; use of beta-carotene supplements in these subgroups is not recommended)


Cholestyramine or{05}
Colestipol or{06}
Mineral oil or{07}{10}
Neomycin{08}{09}{10}    (concurrent use may interfere with the absorption of beta-carotene or vitamin A; requirements for vitamin A may be increased in patients receiving these medications)


Vitamin A{01}    (for treatment of vitamin A deficiency, vitamin A should fulfill normal vitamin A requirements; additional beta-carotene supplementation may not be necessary)


Vitamin E    (concurrent use of vitamin E may facilitate absorption and utilization of beta-carotene and may reduce toxicity of vitamin A {17} {18})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Anorexia or{52}{53}
Hepatic function impairment or{01}
Renal impairment{01}    (may lead to an increase of serum beta-carotene concentrations)


Hypervitaminosis A{38}
Sensitivity to beta-carotene

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Beta-carotene concentrations, plasma and
Vitamin A concentrations, plasma{01}    (determinations recommended to confirm deficiency; plasma vitamin A concentrations are not necessarily indicative of vitamin A nutritional status because of significant hepatic storage, although low concentrations correlate with deficiency)




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Carotenodermia (yellowing of palms, hands, or soles of feet, and to a lesser extent the face)—develops after 2 to 6 weeks of therapy{01}{16}{22}{23}

Incidence rare
    
Arthralgia (joint pain){01}
    
diarrhea {22}
    
dizziness {16}
    
ecchymoses (unusual bleeding or bruising){01}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Beta-carotene (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Description of use
Description should include function in the body; indications for use; signs of vitamin A deficiency; conditions that may cause deficiency of vitamin A; and unproven uses


Importance of diet

For use as a dietary supplement
Importance of proper nutrition; supplement may be desired because of inadequate dietary intake

Importance of relationship between diet and decreased risk of heart disease and certain cancers

Food sources of beta-carotene; effects of processing

Not using vitamins as substitute for balanced diet

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to beta-carotene

Proper use of this medication

For use as a dietary supplement
» Proper dosing

Function of beta-carotene in body

Missed dose: No cause for concern because of length of time necessary for depletion; remembering to take as directed

For use in photosensitivity
» Proper dosing

Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medicine
Not taking beta-carotene supplements if history of smoking or asbestos exposure


Side/adverse effects
Yellow discoloration of skin is to be expected; if taking as nutritional supplement, may be a sign that the dose is too high


General Dosing Information
Because of the infrequency of vitamin A deficiency alone, combinations of several vitamins are commonly administered. Many commercial vitamin complexes are available.

Therapy as a nutritional supplement may be discontinued when liver storage of vitamin A is determined to be adequate.

Diet/Nutrition
Although most manufacturers still label their beta-carotene products in terms of Units (U) of vitamin A activity, the preferred way of designating activity is in retinol equivalents (RE). Six micrograms of beta-carotene is equivalent to 1 RE and 10 Units of vitamin A activity. {17} {27} {32}

It has been documented that individuals who consume diets containing high levels of dietary beta-carotene have a reduced risk of cardiovascular disease and certain types of cancer. {49} {50}

The best dietary sources of beta-carotene include carrots; {21} dark green leafy vegetables, such as spinach; {17} {21} {24} green leafy lettuce; {21} {24} sweet potatoes; broccoli; cantaloupe; {36} {37} and winter squash {21}. {17} Ordinary cooking does not destroy beta-carotene. {24}


Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

BETA-CAROTENE CAPSULES USP

Usual adult and adolescent dose
Vitamin A deficiency (prophylaxis)
Oral, 1000 to 2500 RE (the equivalent of 10,000 to 25,000 Units of vitamin A activity or 6 to 15 mg of beta-carotene) per day.

[Photosensitivity reaction suppressant]1
Oral, 5000 to 50,000 RE (the equivalent of 50,000 to 500,000 Units of vitamin A activity or 30 to 300 mg of beta-carotene) per day. {54}

[Polymorphous light eruption suppressant]1
Oral, 12,500 to 30,000 RE (the equivalent of 125,000 to 300,000 Units of vitamin A activity or 75 to 180 mg of beta-carotene) per day. {03}


Usual pediatric dose
Vitamin A deficiency (prophylaxis)
Oral, 500 to 1000 RE (the equivalent of 5000 to 10,000 Units vitamin A activity or 3 to 6 mg of beta-carotene) per day. {39}

[Photosensitivity reaction suppressant]1 or
[Polymorphous light eruption suppressant]1
Oral, 5000 to 25,000 RE (the equivalent of 50,000 to 250,000 Units of vitamin A activity or 30 to 150 mg of beta-carotene) per day. {11} {54}


Strength(s) usually available
U.S.—


10,000 Units of vitamin A activity (6 mg of beta-carotene) (OTC)[Generic]


25,000 Units of vitamin A activity (15 mg of beta-carotene) (OTC) [Max-Caro{41}][Generic]


50,000 Units of vitamin A activity (30 mg of beta-carotene) (OTC) [Lumitene{01}]

Canada—


10,000 Units of vitamin A activity (6 mg of beta-carotene) (OTC)[Generic]


25,000 Units of vitamin A activity (15 mg of beta-carotene) (OTC)[Generic]

Note: Some strengths of these beta-carotene preparations may exceed the dosage range recommended by USP DI Advisory Panels based on the amount necessary to meet normal nutritional needs.


Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.


BETA-CAROTENE TABLETS

Usual adult and adolescent dose
See Beta-carotene Capsules USP.

Usual pediatric dose
See Beta-carotene Capsules USP.

Strength(s) usually available
U.S.—


10,000 Units of vitamin A activity (6 mg of beta-carotene) (OTC)[Generic]{43}


25,000 Units of vitamin A activity (15 mg of beta-carotene) (OTC)[Generic]

Canada—


25,000 Units of vitamin A activity (15 mg of beta-carotene) (OTC)[Generic]

Note: Some strengths of these beta-carotene preparations may exceed the dosage range recommended by USP DI Advisory Panels based on the amount necessary to meet normal nutritional needs.


Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.


BETA-CAROTENE CHEWABLE TABLETS

Usual adult and adolescent dose
See Beta-carotene Capsules USP.

Usual pediatric dose
See Beta-carotene Capsules USP.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


5000 Units of vitamin A activity (3 mg of beta-carotene) (OTC)[Generic]{47}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.



Revised: 07/09/1997



References
  1. Lumitene package insert (Tischon—US) Rec 11/96.
  1. Thomsen K, Schmidt H, Gischer A. Beta-carotene in erythropoietic protophyria: 5 years experience. Dermatologica 1979; 159: 82-86.
  1. Rakel RE, editor. Conn's current therapy 1990. Philadelphia: W.B. Saunders Company, 1990: 775.
  1. Parrish J, Vine M, Morison W, et al. Comparison of PUVA and beta-carotene in the treatment of polymorphous light erruption. Br J Dermatol 1979; 100: 187-91.
  1. Questran Light package insert (Bristol Labs—US) Rev 3/89, Rec 8/89.
  1. Colestid package insert (Upjohn—US) Rev 9/88, Rec 3/89.
  1. Hansten PD, Horn JR. Drug interactions. 6th ed. Philadelphia: Lea & Febiger, 1989: 412.
  1. Shinn AF, Shrewsbury RP. EDI, evaluation of drug interactions, 3rd ed. St. Louis: Mosby, 1985: 630.
  1. Neomycin tablets package insert (Lilly—US) Rev 4/88, Rec 1/89.
  1. Tatro DS, editor. Drug interaction facts. St. Louis: Facts and Comparisons, 1990: 763-4.
  1. Hurwitz S, editor. Clinical pediatric dermatology. Philadelphia: W. B. Saunders, 1981: 71-72.
  1. Hennekens CH, Buring JE, Manson JE, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 1996; 334: 1145-9.
  1. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994; 330: 1029-37
  1. Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996; 334: 1150-5.
  1. Shiau A, Mobarhan S, Stacewica-Sapuntzakis M, et al. Effects of diet on absorption of beta-carotene. J Am Coll Nutr 1990; 9(5): 533.
  1. Dimitrov N, Meyer C, Ullrey D, et al. Bioavailability of beta-carotene in humans. Am J Clin Nutr 1988; 48: 298-304.
  1. National Research Council. Recommended dietary allowances. 10th ed. Washington DC: National Academy Press, 1989: 78-92.
  1. Gilman AG, Goodman LS, Rall TW, Murad F, editors. Goodman and Gilman's pharmacologic basis of therapeutics. 7th ed. New York: Macmillan, 1985: 1573-82.
  1. Aquasol A parenteral package insert (Rorer—US) Rev 2/88, Rec 8/90.
  1. Brubacher G, Weiser J. The vitamin A activity of beta-carotene. Int J Vitam Nutr Res 1985; 55: 5-15.
  1. Olson J. Recommended dietary intakes (RDI) of vitamin A in humans. Am J Clin Nutr 1987; 45: 704-16.
  1. McEvoy GK, editor. AHFS Drug information 90. Bethesda, MD: American Society of Hospital Pharmacists, 1990: 2108-9.
  1. Micozzi M, Brown E, Taylor P, et al. Carotenodermia in men with elevated carotenoid intake from foods and beta-carotene supplements. Am J Clin Nutr 1988; 48: 1061-4.
  1. Micozzi M, Beecher G, Taylor R, et al. Carotenoid analysis of selected raw and cooked foods associated with lower risk of cancer. J Natl Cancer Inst 1990; 82(4): 282-5.
  1. Personal communication, Roche, 1/19/91.


  1. Open
  1. Bieri J, McKenna M. Expressing dietary values for fat-soluble vitamins: changes in concepts and terminology. Am J Clin Nutr 1981; 34: 289-95.
  1. Open
  1. Open
  1. Bertram J. Rationale and strategies for chemoprevention of cancer in humans. Cancer Res 1987; 47: 3012-31.
  1. Committee on Nutritional Status during Pregnancy, National Academy of Sciences. Washington DC: National Academy Press, 1990: 19-22.
  1. National Research Council. Recommended dietary allowances. 9th ed. Washington DC: National Academy Press, 1980; 57.
  1. Mathews-Roth M, Pathak M, Fitzpatrick T, et al. Beta-carotene as an oral photoprotective agent in erythropoietic protoporphyria. JAMA 1974; 228(8): 1004-8.
  1. Rakel RE, editor. Conn's current therapy. Philadelphia: W.B. Saunders Company, 1991: 396-7.
  1. Reviewer comment, 1991.
  1. Panel comment, 1991.
  1. Reviewer comment, 1991.
  1. Panel consensus, 1991.
  1. Reviewer comment, 1991.
  1. Open
  1. Olin BR, editor, Drug facts and comparisons. St. Louis: Facts and Comparisons Inc, April 1988: 744.
  1. PDR Physicians' desk reference. 47th ed. Montvale, NJ: Medical Economics Data, 1993: 1962.
  1. Open
  1. Open
  1. Open
  1. Open
  1. Open
  1. Nutrition and Electrolytes Advisory Panel Meeting, 1/95.
  1. Ziegler R. A review of epidemiologic evidence that carotenoids reduce the risk of cancer. J Nutr 1989; 119: 116-22.
  1. Personal communication, 1996.
  1. Panelist comment, 1996
  1. Curran-Celentano J, Erdman JW, Nelson RA, et al. Alterations in vitamin A and thyroid hormone status in anorexia nervosa and associated disorders. Am J Clin Nutr 1985; 42: 1183-91.
  1. Thibault L, Roberge AG. The nutritional status of subjects with anorexia nervosa. Int J Vitam Nutr Res 1987; 57: 447-52.
  1. Personal communication, 1996.
  1. Albanes D, Heinonen OP, Taylor PR, et al. -Tocopherol and β-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. J Natl Cancer Inst 1996; 88: 1560-70.
  1. Panelist comment, 1997.
  1. Palan PR, Goldberg GL, Basu J, et al. Lipid-soluble antioxidants: beta-carotene and alpha-tocopherol levels in breast and gynecologic cancers. Gynecol Oncol 1994; 55(1): 72-7.
Hide
(web3)