Comprehensive Guide to Beta-Carotene

Beta-CaroteneDr. James Meschino DC, MS, ND
Introduction
Beta-Carotene is one of 30-50 carotenoids found in plant foods that can be converted by the body into Vitamin A. Beta-Carotene is a fat-soluble compound that is absorbed intact in the presence of bile salts from the intestine. Beta-Carotene is made up of two Vitamin A molecules (attached together). Within intestinal cells they are split to yield retinol (preformed Vitamin A). Approximately one third of all the carotene in food can be converted into Vitamin A. For Beta-Carotene specifically, about one-sixth is available to become Vitamin A, if the body requires it.
Absorption and Metabolism

The splitting of Beta-Carotene (and other carotenes) into retinol within intestinal cells is well regulated to help guard against Vitamin A toxicity. The retinol that is formed from Beta-Carotene enters the chylomicron and is metabolized from that point forward as preformed Vitamin A. Chylomicrons primarily deliver Beta-Carotene to the liver, where they are repackaged within another lipoprotein carrier system known as the very-low-density lipoprotein.

Beta-Carotene (and other carotenoids) enters the bloodstream from the liver and is transported to peripheral tissue by very-low density lipoproteins and low-density lipoproteins (VLDL and LDL, which is the remnant particle of VLDL after triglycerides are removed by fat cells, muscle fibers and other tissues). In contrast, Vitamin A is transported form the liver attached to retinal-binding protein (RBP). Beta-Carotene is stored in fat tissues, and the adrenal glands, testes, ovaries, rather than the liver and is responsible for the yellowish tinge to the skin when large amounts are stored (carotenodermia). However, carotenodermia is considered to be a nonpathological, reversible condition; not associated with any health risks. Some conversion of Beta-Carotene may take place in the liver and lungs. About 40-60% of Beta-Carotene is absorbed from food. Of interest is the fact that Beta-Carotene supplements are better absorbed than carotenes from food. Beta-Carotene comprises 20-25% of the total serum carotene level.

Functions
Vitamin A Precursor: because Beta-Carotene can be converted into Vitamin A, it supports Vitamin A nutritional status and all vitamin A-related functions.

Antioxidant: Beta-Carotene is an antioxidant and does not need to be converted into Vitamin A to perform antioxidant functions.

Immune System: Beta-Carotene appears to enhance thymus gland function and increases interferon's stimulatory action on the immune system.1

Other Functions: as described below, Beta-Carotene exhibits a number of immune-enhancing and anti-cancer propertied, and has therefore, been tested in patients with immune-compromised states, precancerous, and cancerous conditions, as well as in patients at high risk in developing certain cancers.

Beta-Carotene Supplementation

Compromised Immune Function

A number of studies reveal that older subjects can enhance various aspects of immune function through the supplementation of at least 15 mg of Beta-Carotene (25,000 I.U.) per day. The immune system tends to weaken as humans age, thus researchers have examined various nutrients that may prevent or reverse age-related decline in immune function. High doses of Beta-Carotene have been used in the treatment of immune compromised states and studies on normal human volunteers indicate that supplementation with 180 mg (300,000 I.U.) of Beta-Carotene per day, significantly increased in the number of T-helper cells by approximately 30% after seven days of supplementation, with a 30% increase in a total T-cell count after 14 days. This may be of great significance in HIV/AIDS patients, who have low T-helper cell counts and other parameters of immune function compromise.2-5

Beta-Carotene supplementation at 50,000 I.U., twice per day administered to AIDS patients has resulted in a 66% rise in total lymphocyte count and a small rise in T-helper cell levels. With discontinuation of Beta-Carotene supplementation, lymphocyte and T-helper cell counts returned to base line levels within six weeks.2 In a second study, 60 mg (100,000 I.U.) administered to seven AIDS patients resulted in a rise of T-helper cells over the four-week trial period. This is important as it is the T-helper cell (CD$) count that is adversely affected by the HIV virus and largely accounts for the dramatic reduction in immune function seen in HIV and AIDS patients.27 Not all Beta-Carotene studies with AIDS patients have shown these benefits, but the lack of adverse side effects with Beta-Carotene suggests that it can be used safely as a complementary therapy in these cases.2 Moderate dosages of Beta-Carotene supplementation may help to slow down or halt the age-related decline in immune function that increases susceptibility to infection and possibly cancer, as we age. This is true as well for other antioxidant vitamins (Vitamin C, Vitamin E, Vitamin A) and the minerals zinc and selenium.3,4,5 was introduced. Moderate doses of beat-carotene supplementation may help to slow down or halt the age-related decline in immune function that increases susceptibility to infection and possible cancer as we age. This is true as well for other antioxidant vitamins and the minerals zinc and selenium.

Cancer Prevention

At this time it is inadvisable to give high dose Beta-Carotene supplementation (50,000 I.U. or greater) to patients who smoke one pack of cigarettes per day or more. The Alpha-Tocopherol, Beta-Carotene study and the CARET study suggested that Beta-Carotene, in these cases, may slightly increase the risk of lung cancer, although this needs confirmation.6,7 However, Beta-Carotene does demonstrate a number of anti-cancer properties and has been shown to reverse leukoplakia – a pre-cancerous condition of the oral cavity, as well as early-stage cervical dysplasia, a pre-cancerous condition of the uterine cervix.8-13 In the Linxian China study, the combination of modest dosages of Beta-Carotene, Vitamin E, and selenium significantly reduced stomach and esophageal cancers, as well as total cancer incidence in high-rish individuals, compared to other vitamin and mineral combinations.26 Beta-Carotene is an antioxidant, an immune system modulator and enahances cellular differentiation of epithelial cells. All of these effects are associates with the prevention of cancer and the reversal of some early stage cancers and states of dysplasia (pre-cancerous states).4-13

Cervical Dysplasia

Beta-Carotene has been shown to influence cellular differentiation of surface lining cells (epithelial cells) and enhances immune-system function. Beta-Carotene has been shown to halt the progression of cervical dysplasia and cause a reversal in some cases involving early and moderate stages of this condition, which is known to be a pre-cancerous condition.12,13,18

Cardiovascular Disease

Beta-Carotene supplementation has been shown to decrease oxidation of LDL-cholesterol, but to a lesser degree than Vitamin E. In this regard, it may help to reduce the risk of cardiovascular disease, as oxidized LDL-cholesterol appears to be more inclined to narrow arteries as part of the atherosclerotic process that leads to heart disease and ischemic stroke. However, evidence is stronger for Vitamin E. Both Vitamin E and Beta-Carotene are transported through the bloodstream within VLDL and LDL lipoproteins, where they are able to act as antioxidants in regards to reducing the oxidation of fatty acids and cholesterol within these lipoproteins (VLDL and LDL).14,15,16 The Physicians Helath Study failed, to show a benefit in cardiovascular disease reduction with Beta-Carotene supplementation of 50 mg (83,333 I.U.), taken every other day for 12 years. However, a subgroup analysis of these 22,000 medical doctors showed that of the 333 physicians prior history of heart disease, Beta-Carotene supplementation produced a small reduction in risk of fatal and non-fatal heart attack.30 A number of prospective studies have suggested that higher intakes of Beta-Carotene is associated with a significant reduction in heart attack and stroke, as highlighted in the Western Electric Study in Chicago and a study of Italian women by A Tavani, et al.28,29

Dosage

1. Compromised Immune Function: 50,000 I.U., but a dosage of up to 3,000,000I.U. has been used in short term studies2-5

2. HIV/AIDS: 50,000 I.U., twice daily has been used with some success2,27

3. Oral Leukoplakia: 50,000-1000,000 I.U. per day9,10

4. Cervical Dysplasia: 50,000-100,000 I.U. per day12,13

5. Cancer Treatment Support: 75,000-100,000 I.U. per day (lung cancer would be an exception)11

6. Heart Diseases and Cardiovascular Health: 10,000-75,000 I.U.14,30

7. General Wellness: 10,000-25,000 I.U. is commonly consumed

Adverse Side Effects and Toxicity
Overall, the experimental animal data demonstrate a high level of Beta-Carotene safety and in human trials using doses of 20-180 mg/d (up to 300,000 I.U./d) to treat patients with the genetic disease erythropoietic protoporphryria. These large doses did not produce any toxic effects. Other studies have confirmed this. Babies born to mothers with carotenemia show no untoward effects or defects and are otherwise normal.17
Drug-Nutrient Interactions

Bile Acid Sequestrants, such as cholestyramine and colestipol may decrease absorption of Beta-Carotene (as they do other fat-soluble vitamins).19,20

Proton Pump Inhibitors such as omeprazole are known to decrease Beta-Carotene absorption.21

Other drugs that impair Beta-Carotene absorption include:

  • colchicines22
  • mineral oil23
  • neomycin24
  • orlistat25
References
Standard Textbooks of Nutritional Science:

   - Shils M, Shike M, Olson J, Ross C. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Lippincott Williams & Wilkins; 1993.

   - Escott-Stump S, Mahan LK, editors. Food, Nutrition and Diet Therapy. 10th ed. Philadelphia, PA: W.B. Saunders Company; 2000.

   - Bowman B, Russell RM, editors. Present Knowledge in Nutrition, 8th ed. Washington, DC:.ILSI Press; 2001.

   - Kreutler PA, Czajka-Narins DM, editors. Nutrition in Perspective. 2nd ed. Upper Saddle River, NJ: Prentice Hall Inc.; 1987.

Coodley GO, Nelson HD, Loveless MO, Folk C. Beta-Carotene in HIV infection. J AIDS 1993;6:272-6.

Santos MS, Gaziano JM, Leka LS, Beharka AA, Hennekens CH, Meydani SN. B-Carotene-induced enhancement of natural killer cell activity in elderly men: an investigation of the role of cytokines. Am J Clin Nutr 1998;68:164-70.

Bogden JD, Bendich A, Kemp FW. Daily micronutrient supplements enhance delayed hypersensitivity skin test responses in older people. Am J Clin Nutr 1990;60:437-47.

Santos MS, Meydani SN, Leka L, Wu D, Fotouhi N, Meydani M, et al. Natural killer cell activity in elderly men is enhanced by B-Carotene supplementation. Am J Clin Nutr 1996;64:772-7.

The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med 1994;330:1029-35.

Omenn GS, Goodman G, Thornquist M. The Beta-Carotene and retinal efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers. Cancer Res 1994;54:2038-43.

Ziegler RG. Vegetables, fruits and carotenoids and the risk of cancer. Am J Clin Nutr 1991;53(1):251-64.

Stich HF, Rosin MP, Vallejera MO. Reduction with Vitamin A and Beta-Carotene administration of proportion of micronucleated buccal mucosal cells in Asian betel nut and tobacco chewers. Lancet 1984;1:1204-6.

Garewal HS. Emerging role of Beta-Carotene and antioxidant nutrients in prevention of oral cancer. Archives of otolaryngology. Head Neck Surgery 1995;121(2):141-4.

Lockwood K, Moesgaard S, Hanioka T, Folkers K. Apparent partial remission of breast cancer in high risk patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Molec Aspects Med 1994;15(Suppl):231S-40S.

Van Eenwyk J, Davis FG, Bowne PE. Dietary and serum carotenoids and cervical intraepithelial neoplasia. Int J Cancer 1991;48:34-8

Liu T, Soong SJ, Wilson NP, Craig CB, Cole P, Macaluso M, et al. A case control study of nutritional factors and cervical dysplasia. Cancer Epidemiol Biomarkers Prev 2. 1993;2(6):525-30.

Hennekens CH, Gaziano JM. Antioxidants and heart disease: epidemiology and clinical evidence. Clin Cardio 1993;16(Suppl I):I10-I5.

Reaven PD, Khouw A, Beltz WF, Parthasarathy S, Witztum JL. Effect of dietary antioxidant combination in humans. Protection of LDL by vitamin E but not by Beta-Carotene. Arteriosol Thrombosis 1993;13:590-600.

Gaziano JM, et al. Dietary Beta-Carotene intake and decreased cardiovascular mortality in an elderly cohort. J Am College of Cardiology 1992;19:377.

Hathcock JN, Hattan DG, Jenkins MY, McDonald JT, Sundaresan PR, Wilkening VL. Evaluation of Vitamin A toxicity. Am J Clin Nutr 1990:52:183-202.

deVet HC, Knipschild PG, Willebrand D, Schouten HJ, Sturmans F. The effect of Beta-Carotene on the regression and progression of cervical dysplasia: a clinical experiment. J Clin Epidemiol 1991:44:273-93.

Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987;2(1):10-32.

Probstfield JL, Lin TL, Peters J, Hunninghake DB. Carotenoids and Vitamin A: The effect of hypocholesterolemic agents on serum levels. Metabolism 1985;34(1):88-91.

Tang G, Serfaty-Lacrosniere C, Camilo ME, Russell RM. Gastric acidity influences the blood response to a Beta-Carotene dose in humans. Am J Clin Nutr 1996;64(4):622-6.

Race TF, Paes IC, Faloon WW. Intestinal malabsorption induced by oral colchicines. Comparison with neomycin and cathartic agents. Am J Med Sci 1970;259(1):32-41.

Diarrhea and Constipation. In: Berkow R, Fletcher AJ, Beers MH, et al, editors. The Merck Manual of Diagnosis and Therapy. 16th ed. Rahway, NJ: Merck Research Laboratories; 1992. p. 810.

Jacobson ED, Faloon WW. Malabsorptive effects of neomycin in commonly used doses. J Am Med Assoc 1961;175:187-90.

Finer N, James WP, Kopelman PG, Lean ME, Williams G. One-year treatment of obesity: A randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor. Int J Obes Relat Metab Disord 2000;24(3):306-13.

Blot WJ, et al. Nutrition intervention trials in Linxian China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 1993;85:1483-92.

Fryburg DA, Mark RJ, Griffith BP, et al. The effect of supplemental beta-carotene on immunologic indices in patients with AIDS: a pilot study. Yale J Biol Med 1995;68(1-2):19-23.

Daviglus ML, Orencia AJ, Dyer AR, et al. Dietary vitamin C, beta-carotene and 30-year risk of stroke: results from the Western Electric Study. Neuroepidiology 1997;16(2):69-77.

Tavani A, Negii E, D'Avanzo, et al. Beta-carotene intake and risk of nonfatal acute myocardial infarction in women. Eur J Epidemiol 1997;13(6):631-7.

Hennekens CH, 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 and 1189-90.