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Beta-Carotene

June 10, 2008 - 7:30am
 
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Beta-Carotene

Principal Proposed Uses
  • Providing the Nutritional Vitamin A Requirement
Probably Ineffective Uses
  • ]]>Cancer Prevention]]>, ]]>Diabetes]]>, ]]>Heart Disease Prevention]]>

Note: All the significant positive evidence for beta-carotene applies to food sources, not supplements.

Beta-carotene belongs to a family of natural chemicals known as ]]>carotenoids]]> . Widely found in plants, carotenoids along with another group of chemicals, bioflavonoids, give color to fruits, vegetables, and other plants.

Beta-carotene is a particularly important carotenoid from a nutritional standpoint, because the body easily transforms it to ]]>vitamin A]]> . While vitamin A supplements themselves can be toxic when taken to excess, it is believed (although not proven) that the body will make only as much vitamin A out of beta-carotene as it needs. Assuming this is true, this built-in safety feature makes beta-carotene the best way to get your vitamin A.

Beta-carotene is also often recommended for another reason: it is an antioxidant, like ]]>vitamin E]]> and ]]>vitamin C]]> . In ]]>observational studies]]> , high intake of carotenoids from food has been associated with reduced risk of various illnesses (including heart disease and cancer). However, observational studies are inherently unreliable, as described ]]>below]]> . In ]]>intervention trials]]> , beta-carotene supplements have not been found to offer any benefits; in fact, when taken in high doses for a long period of time, beta-carotene supplements might slightly increase the risk of heart disease and some forms of cancer.

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Requirements/Sources

Although beta-carotene is not a required nutrient, vitamin A is essential for health, and beta-carotene is converted into vitamin A in the body. The exact conversion factor varies with the circumstances; in general, 2 mcg of beta-carotene in supplement form is thought to be equivalent to 1 mcg of vitamin A. See the article on vitamin A]]> for requirements based on age and sex.

Dark green and orange-yellow vegetables are good sources of beta-carotene. These include carrots, sweet potatoes, squash, spinach, romaine lettuce, broccoli, apricots, and green peppers.

Note: Plant ]]>sterols]]>, used to treat ]]>high cholesterol]]>, may impair absorption of beta-carotene. ]]>81]]>

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Therapeutic Dosages

We are not sure at the present time whether it is advisable to take dosages of beta-carotene supplements much higher than the recommended allowance for nutritional purposes, which is about 1.5 to 1.8 mg daily in adults. Rather than taking doses higher than this, it is probably more advisable to increase your intake of fresh fruits and vegetables.

Therapeutic Uses

There are no well-documented therapeutic uses of beta-carotene, beyond supplying nutritional doses of vitamin A.

Numerous observational studies]]> have found that a high intake of foods rich in carotenoids is associated with a lower incidence of lung cancer, other forms of ]]>cancer]]>, and ]]>heart disease]]> . ]]>1-7]]> However, beta-carotene supplements have not been found to be helpful for preventing these conditions. ]]>8-12]]> In fact, when all major beta-carotene studies are statistically combined through a process called “meta-analysis,” some evidence appears suggesting that long-term usage of beta-carotene at high doses might increase overall death rate, for reasons that are unclear. ]]>82]]>

Similarly, observational evidence links high dietary intake of carotenoids to a lower incidence and/or slowed progression of ]]>cataracts]]> , ]]>macular degeneration]]>, and ]]>osteoarthritis]]> , ]]>13,14,16-18]]> but again there is no reliable evidence that beta-carotene supplements are helpful for these conditions. In fact, a 12-year study of over 22,000 male physicians failed to find that beta-carotene had any effect on the incidence of macular degeneration. ]]>83]]>

Preliminary evidence raised hopes that beta-carotene supplements might increase or preserve immune function or decrease symptoms among people with ]]>HIV]]> . ]]>61,64,65]]> However, other studies found no benefit, ]]>62,63]]> and some evidence hints that too much beta-carotene might actually be harmful. ]]>64,65]]>

Beta-carotene supplements may be helpful for protecting the skin from ]]>sunburn]]> , particularly in people with extreme ]]>sensitivity to the sun]]> , but the evidence regarding this potential use is somewhat contradictory. ]]>26-36]]> One double-blind trial found that faithful daily use of sunscreen was more effective at preventing sun damage to the skin than oral beta-carotene plus sunscreen used as needed. ]]>78]]>

One preliminary study found evidence that beta-carotene might be helpful for cystic fibrosis, by helping prevent lung infections. ]]>37]]>

Another preliminary study suggests that beta-carotene might help prevent exercise-induced asthma. ]]>77]]>

Weak evidence culled from a large double-blind, placebo-controlled study hints that use of beta-carotene over many years might ]]>enhance mental function]]>.]]>84]]>

Beta-carotene has been proposed as a treatment for ]]>alcoholism]]> , ]]>asthma]]> , ]]>depression]]> , ]]>epilepsy]]> , ]]>headaches]]> , ]]>heartburn]]> , ]]>male infertility]]> , ]]>female infertility]]> , ]]>Parkinson's disease]]> , ]]>psoriasis]]> , ]]>rheumatoid arthritis]]> , and ]]>schizophrenia]]> , but there is little to no evidence that it works.

There is some evidence that beta-carotene is not effective for ]]>cervical dysplasia]]>]]>38,72,73,74]]> or ]]>intermittent claudication]]> . ]]>39]]>

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What Is the Scientific Evidence for Beta-Carotene?

Cancer Prevention

The story of beta-carotene and cancer prevention]]> is full of apparent contradictions. It starts in the early 1980s, when the cumulative results of many studies suggested that people who eat a lot of fruits and vegetables are significantly less likely to get cancer. ]]>40,41]]> A close look at the data pointed to carotenoids as the active ingredients in fruits and vegetables. It appeared that a high intake of dietary carotene might significantly reduce the risk of lung cancer, ]]>42]]> bladder cancer, ]]>43]]> breast cancer, ]]>44]]> esophageal cancer, ]]>45]]> and stomach cancer. ]]>46]]>

However, observational studies cannot prove cause and effect. It is always possible that individuals who consume a great deal of carotenoids in the diet are different in other ways; for example, they might exercise more or have healthier lifestyles in other regards.

This is not a purely theoretical issue. For example, based primarily on observational studies, hormone replacement therapy was promoted as a heart-protective treatment for postmenopausal women. However, when ]]>placebo-controlled]]> studies were performed, hormone replacement therapy was shown to slightly increase the risk of heart disease. One possible explanation for this discrepancy is that the apparent benefits of hormone replacement therapy were due to the fact that women who used it tended to belong to a higher socioeconomic class than those who did not. (For a variety of reasons, some of which are not known, higher income is associated with improved health.)

Something similar appears to be the case with beta-carotene. Although individuals who consume foods high in beta-carotene appear to obtain some protection from heart disease and cancer, when researchers gave beta-carotene supplements to study participants, there was no protective effect.

Most studies enrolled people in high-risk groups, such as smokers, because it is easier to see results when you look at people who are more likely to develop cancer to begin with.

The anticancer bubble burst for beta-carotene in 1994 when the results of the Alpha-Tocopherol, Beta-Carotene (ATBC) study became available. ]]>47]]> These results showed that beta-carotene supplements did not prevent lung cancer, but actually increased the risk of getting it by 18%. This trial had followed 29,133 male smokers in Finland who took supplements of about 50 IU of vitamin E (alpha-tocopherol), 20 mg of beta-carotene (more than 10 times the amount necessary to provide the daily requirement of vitamin A), both, or placebo daily for 5 to 8 years. (In contrast to the results for beta-carotene, ]]>vitamin E]]> was found to reduce the risk of cancer, especially prostate cancer.)

In January 1996, researchers monitoring the Beta-Carotene and Retinol Efficacy Trial (CARET) confirmed the prior bad news with more of their own: the beta-carotene group had 46% more cases of lung cancer deaths. ]]>48]]> This study involved smokers, former smokers, and workers exposed to asbestos. Alarmed, the National Cancer Institute ended the $42 million CARET trial 21 months before it was planned to end.

At about the same time, the 12-year Physicians' Health Study of 22,000 male physicians was finding that 50 mg of beta-carotene (about 25 times the amount necessary to provide the daily requirement of vitamin A) taken every other day had no effect—good or bad—on the risk of cancer or heart disease. In this study, 11% of the participants were smokers and 39% were ex-smokers. ]]>49,50]]>

Similarly, another study of beta-carotene supplements failed to find any effect on the risk of cancer in women. ]]>51]]> And, in a final indictment of beta-carotene’s safety and effectiveness, researchers, who combined the results of 12 recent placebo-controlled trials investigating the association between antioxidant supplementation and cancer, found that beta-carotene use was associated with an increased incidence of cancer among smokers.]]>86]]> But the story doesn’t end there. In yet another careful analysis of 4 randomized trials involving 109,394 smokers and former-smokers, researchers found that current smokers who consumed between 20-30 mg of beta-carotene were at a significantly greater risk of developing lung cancer. There was no such risk among former smokers.]]>87]]>

There are several possible explanations for these apparently contradictory findings. As noted above, it is possible that intake of carotenoids as such is unrelated to cancer, and that some unrelated factor common to individuals with a high carotene diet is the cause of the benefits seen in observational trials.

Another possibility is that beta-carotene alone is not effective, and the other carotenoid found in fruits and vegetables may be more important for preventing cancer than beta-carotene. One researcher has suggested that taking beta-carotene supplements depletes the body of these other beneficial carotenoids, and thereby causes a harmful effect. ]]>54]]> In support of this theory, a large study found that consumption of fruits and vegetables is generally associated with lower lung cancer risk, but when beta-carotene is taken, this preventive effect disappears. ]]>79]]>

Heart Disease Prevention

The situation with beta-carotene and heart disease is rather similar to that of beta-carotene and cancer. Numerous studies suggest that carotenoids as a whole can help prevent ]]>heart disease]]> . ]]>55]]> However, isolated beta-carotene may not help prevent heart disease and could actually increase your risk.

The same double-blind intervention trial involving 29,133 Finnish male smokers (mentioned under the discussion of cancer and beta-carotene) found 11% more deaths from heart disease and 15% to 20% more strokes in those participants taking beta-carotene supplements. ]]>56]]>

Similar poor results with beta-carotene were seen in another large, double-blind study of smokers. ]]>57]]> Beta-carotene supplementation was also found to increase the incidence of ]]>angina]]> in smokers. ]]>58]]>

Osteoarthritis

A high dietary intake of beta-carotene is associated with a significantly slower progression of ]]>osteoarthritis]]> , according to a study in which researchers followed 640 individuals over a period of 8 to 10 years. ]]>59]]> However, as with heart disease and cancer, we don't know whether beta-carotene is responsible for this effect. ]]>60]]>

HIV Support

One small, double-blind study suggested that beta-carotene supplements might raise white blood cell count in people with ]]>HIV]]> . ]]>61]]> However, two subsequent larger controlled trials found no significant differences between those taking beta-carotene or placebo in white blood cell count, CD4+ count, or other measures of immune function. ]]>62,63]]>

Evidence from observational studies suggests that higher intakes of ]]>vitamin A]]> or beta-carotene may be helpful; however, caution is in order regarding dosage. ]]>64,65]]> Researchers generally linked higher intake of vitamin A or beta-carotene to lower risk of AIDS and lower death rates, with an important exception: people with the highest intake of either nutrient (more than 11,179 IU per day of beta-carotene or more than 20,268 IU per day of vitamin A) did worse than those who took somewhat less.

Macular Degeneration and Cataracts

Despite promising results from observational studies, intervention trials of beta-carotene for these eye conditions have generally not shown benefit. Beta-carotene proved ineffective for ]]>preventing cataracts]]> in one large study, ]]>15]]> and in another large study, beta-carotene supplements combined with vitamin E and C failed to prevent either macular degeneration or cataracts. ]]>75]]> On a more positive note, one large study found that beta-carotene supplements helped prevent cataracts in study participants who smoked; nonetheless, no benefit was seen in the group as a whole. ]]>80]]>

Cervical Dysplasia

According to a 2-year, double-blind, placebo-controlled study of 141 women with mild ]]>cervical dysplasia]]> (a precancerous condition of the cervix), beta-carotene, taken at a dosage of 30 mg daily along with 500 mg of ]]>vitamin C]]> , does not help to reverse the dysplasia. ]]>38]]> Negative results were seen in other trials of beta-carotene as well. ]]>72,73,74]]>

Intermittent Claudication

A double-blind, placebo-controlled trial of 1,484 individuals with ]]>intermittent claudication]]> found no benefit from beta-carotene (20 mg daily), ]]>vitamin E]]> (50 mg daily), or a combination of the two. ]]>39]]>

Diabetes

In a very large study involving over 29,000 male smokers, researchers failed to find benefit of beta-carotene (20 mg/day), alpha-tocopherol (50 IU/day), or the two taken together for the prevention of type 2 diabetes over a 5 to 8 year period.]]>85]]>

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Safety Issues

At recommended dosages, beta-carotene is believed to be very safe. The only side effects reported from beta-carotene overdose are diarrhea and a yellowish tinge to the hands and feet. These symptoms disappear once you stop taking beta-carotene or reduce your dose.

However, long-term use of beta-carotene supplements, especially at doses considerably above the amount necessary to supply adequate vitamin A, might slightly increase the risk of heart disease and certain forms of cancer, and raise overall death rate. 67-71, 82]]> The solution: Eat plenty of fresh fruits and vegetables, and get your beta-carotene that way.

In addition, some evidence suggests that beta-carotene supplements might cause ]]>alcoholic liver disease]]> to develop more rapidly in individuals who abuse alcohol. ]]>66,76]]>

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References

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2.   Ziegler RG. A review of epidemiologic evidence that carotenoids reduce the risk of cancer. J Nutr . 1989;119:116-122.

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5.   Rock CL, Saxe GA, Ruffin MT IV, et al. Carotenoids, vitamin A, and estrogen receptor status in breast cancer. Nutr Cancer . 1996;25:281-296.

6.   Zheng W, Sellers TA, Doyle TJ, et al. Retinol, antioxidant vitamins, and cancer of the upper digestive tract in a prospective cohort study of postmenopausal women. Am J Epidemiol . 1995;142:955-960.

7.   Kohlmeier L, Hastings SB. Epidemiologic evidence of a role of carotenoids in cardiovascular disease prevention. Am J Clin Nutr . 1995;62(6 suppl):1370S-1376S.

8.   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;330:1029-1035.

9.   Rapola JM, Virtamo J, Ripatti S, et al. Randomized trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Lancet . 1997;349:1715-1720.

10.   Rapola JM, Virtamo J, Haukka JK, et al. Effect of vitamin E and beta carotene on the incidence of angina pectoris. A randomized, double-blind, controlled trial. JAMA. 1996;275:693-698.

11.   White WS, Stacewicz-Sapuntzakis M, Erdman JW Jr, et al. Pharmacokinetics of beta-carotene and canthaxanthin after ingestion of individual and combined doses by human subjects. J Am Coll Nutr . 1994;13:665-671.

12.   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;334:1150-1155.

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32.   Gollnick HP, Hopfenmuller W, Hemmes C, et al. Systemic beta carotene plus topical UV sunscreen are an optimal protection against harmful effects of natural UV-sunlight: results of the Berlin-Eilath study. Eur J Dermatol. 1996;6:200-205.

33.   Lee J, Jiang S, Levine N, et al. Carotenoid supplementation reduces erythema in human skin after simulated solar radiation exposure. Proc Soc Exp Biol Med. 2000;223:170-174.

34.   Stahl W, Heinrich U, Jungmann H, et al. Carotenoids and carotenoids plus vitamin E protect against ultraviolet light-induced erythema in humans. Am J Clin Nutr. 2000;71:795-798.

35.   Garmyn M, Ribaya-Mercado JD, Russel RM, et al. Effect of beta-carotene supplementation on the human sunburn reaction. Exp Dermatol. 1995;4:104-111.

36.   Wolf C, Steiner A, Honigsmann H. Do oral carotenoids protect human skin against UV erythema, psoralen phototoxicity, and UV-induced DNA damage? J Invest Dermatol. 1988;90:55-57.

37.   Renner S, Rath R, Rust P, et al. Effects of beta-carotene supplementation for six months on clinical and laboratory parameters in patients with cystic fibrosis. Thorax. 2001;56:48-52.

38.   Mackerras D, Irwig L, Simpson JM, et al. Randomized double-blind trial of beta-carotene and vitamin C in women with minor cervical abnormalities. Br J Cancer. 1999;79:1448-1453.

39.   Tornwall ME, Virtamo J, Haukka JK, et al. The effect of alpha-tocopherol and beta-carotene supplementation on symptoms and progression of intermittent claudication in a controlled trial. Atherosclerosis. 1999;147:193-197.

40.   Steinmetz KA, Potter JD. Vegetables, fruit, and cancer prevention: a review. J Am Diet Assoc . 1996;96:1027-1039.

41.   Ziegler RG. A review of epidemiologic evidence that carotenoids reduce the risk of cancer. J Nutr . 1989;119:116-122.

42.   Flagg EW, Coates RJ, Greenberg RS. Epidemiologic studies of antioxidants and cancer in humans. J Am Coll Nutr . 1995;14:419-427.

43.   Vena JE, Graham S, Freudenheim J, et al. Diet in the epidemiology of bladder cancer in western New York. Nutr Cancer . 1992;18:255-264.

44.   Rock CL, Saxe GA, Ruffin MT IV, et al. Carotenoids, vitamin A, and estrogen receptor status in breast cancer. Nutr Cancer . 1996;25:281-296.

45.   Zheng W, Sellers TA, Doyle TJ, et al. Retinol, antioxidant vitamins, and cancer of the upper digestive tract in a prospective cohort study of postmenopausal women. Am J Epidemiol . 1995;142:955-960.

46.   Zheng W, Sellers TA, Doyle TJ, et al. Retinol, antioxidant vitamins, and cancer of the upper digestive tract in a prospective cohort study of postmenopausal women. Am J Epidemiol . 1995;142:955-960.

47.   Albanes D, Heinonen OP, Huttunen JK, et al. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. Am J Clin Nutr . 1995;62(6 suppl):1427S-1430S.

48.   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;334:1150-1155.

49.   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;334:1145-1149.

50.   Frieling UM, Schaumberg DA, Kupper TS, et al. A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the physicians' health study. Arch Dermatol. 2000;136:179-184.

51.   Lee IM, Cook NR, Manson JE, et al. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women's Health Study. J Natl Cancer Inst. 1999;91:2102-2106.

52.   Albanes D, Heinonen OP, Huttunen JK, et al. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. Am J Clin Nutr . 1995;62(6 suppl):1427S-1430S.

53.   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;334:1150-1155.

54.   White WS, Stacewicz-Sapuntzakis M, Erdman JW Jr, et al. Pharmacokinetics of beta-carotene and canthaxanthin after ingestion of individual and combined doses by human subjects. J Am Coll Nutr . 1994;13:665-671.

55.   Kohlmeier L, Hastings SB. Epidemiologic evidence of a role of carotenoids in cardiovascular disease prevention. Am J Clin Nutr . 1995;62(6 suppl):1370S-1376S.

56.   [No authors listed]. 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;330:1029-1035.

57.   Rapola JM, Virtamo J, Ripatti S, et al. Randomized trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Lancet . 1997;349:1715-1720.

58.   Rapola JM, Virtamo J, Haukka JK, et al. Effect of vitamin E and beta carotene on the incidence of angina pectoris. A randomized, double-blind, controlled trial. JAMA. 1996;275:693-698.

59.   McAlindon TE, Jacques P, Zhang Y, et al. Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis? Arthritis Rheum . 1996;39:648-656.

60.   McAlindon TE, Jacques P, Zhang Y, et al. Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis? Arthritis Rheum . 1996;39:648-656.

61.   Coodley GO, Nelson HD, Loveless MO, et al. Beta-carotene in HIV infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1993;6:272-276.

62.   Coodley GO, Coodley MK, Lusk R, et al. Beta-carotene in HIV infection: an extended evaluation. AIDS . 1996;10:967-973.

63.   Constans J, Delmas-Beauvieux MC, Sergeant C, et al. One-year antioxidant supplementation with beta-carotene or selenium for patients infected with human immunodeficiency virus: a pilot study [letters]. Clin Infect Dis . 1996;23:654-656.

64.   Tang AM, Graham NHM, Kirby AJ, et al. Dietary micronutrient intake and risk of progression to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus type 1 (HIV-1)-infected homosexual men. Am JEpidemiol. 1993;138:937-951.

65.   Tang AM, Graham NM, Saah AJ. Effects of micronutrient intake on survival in human immunodeficiency virus type 1 infection. Am JEpidemiol. 1996;143:1244-1256.

66.   Leo MA, Lieber CS. Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr. 1999;69:1071-1085.

67.   [No authors listed]. 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;330:1029-1035.

68.   Rapola JM, Virtamo J, Ripatti S, et al. Randomized trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Lancet . 1997;349:1715-1720.

69.   Rapola JM, Virtamo J, Haukka JK, et al. Effect of vitamin E and beta carotene on the incidence of angina pectoris. A randomized, double-blind, controlled trial. JAMA. 1996;275:693-698.

70.   White WS, Stacewicz-Sapuntzakis M, Erdman JW Jr, et al. Pharmacokinetics of beta-carotene and canthaxanthin after ingestion of individual and combined doses by human subjects. J Am Coll Nutr . 1994;13:665-671.

71.   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;334:1150-1155.

72.   Keefe KA, Schell MJ, Brewer C, et al. A randomized, double blind, phase III trial using oral beta-carotene supplementation for women with high-grade cervical intraepithelial neoplasia. Cancer Epidemiol Biomarkers Prev. 2001;10:1029-1035.

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75.   Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta-carotene for age-related cataract and vision loss: AREDS report no. 9. Arch Ophthalmol . 2001;119:1439-1452.

76.   Ni R, Leo MA, Zhao J, Lieber CS. Toxicity of beta-carotene and its exacerbation by acetaldehyde in HepG2 cells. Alcohol. 2001;36:281-285.

77.   Neuman I, Nahum H, Ben-Amotz A. Prevention of exercise-induced asthma by a natural isomer mixture of beta-carotene. Ann Allerg Asthma Immunol . 1999;82:549-553.

78.   Darlington S, Williams G, Neale R, et al. A randomized controlled trial to assess sunscreen application and beta-carotene supplementation in the prevention of solar keratoses. Arch Dermatol. 2003;139:451-455.

79.   Neuhouser ML, Patterson RE, Thornquist MD, et al. Fruits and vegetables are associated with lower lung cancer risk only in the placebo arm of the beta-carotene and retinol efficacy trial (CARET). Cancer Epidemiol Biomarkers Prev. 2003;12:350-358.

80.   Christen WG, Manson JE, Glynn RJ, et al. A randomized trial of beta-carotene and age-related cataract in US physicians. Arch Ophthalmol. 2003;121:372-378.

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Last reviewed May 2008 by EBSCO CAM Review Board]]>

Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.

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