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"Which form is best?
Most beta-carotene in supplements is synthetic, consisting of only one molecule called all trans beta-carotene. Natural beta-carotene, found in food, is made of two molecules—all trans beta-carotene and 9-cis beta-carotene.
Researchers originally saw no meaningful difference between natural and synthetic beta-carotene. This view was questioned when the link between beta-carotene-containing foods (all natural) and lung cancer prevention2 was not duplicated in studies using synthetic pills.3 In smokers, synthetic beta-carotene has apparently caused an increased risk of lung cancer4 5 6 and disease of the blood vessels7 in double-blind research. Animal research has begun to identify the ways in which synthetic beta-carotene might cause damage to lungs, particularly when animals are exposed to cigarette smoke.8
Much of natural beta-carotene is in the all trans molecule form—the same as synthetic beta-carotene. Moreover, much of the 9-cis molecule found only in natural beta-carotene is converted to the synthetic molecule before it reaches the bloodstream.9 Also, absorption of 9-cis beta-carotene appears to be poor,10 though some researchers question this finding.11
Despite the overlap between natural and synthetic forms, natural beta-carotene may possibly have activity that is distinct from the synthetic form. For example, studies in both animals12 and humans13 have shown that the natural form has antioxidant activity that the synthetic form lacks. Also, in one trial, pre-cancerous changes in people reverted to normal tissue with natural beta-carotene supplements, but not with synthetic supplements.14 Israeli researchers have investigated whether the special antioxidant effects of natural beta-carotene might help people suffering from asthma attacks triggered by exercise.15 People with asthma triggered by exercise were given 64 mg per day of natural beta-carotene for one week. In that report, 20 of 38 patients receiving natural beta-carotene were protected against exercise-induced asthma. However, because synthetic beta-carotene was not tested, the difference between the activity of the two supplements cannot be deduced from this report.
Increasingly, doctors are recommending that people supplement only with natural beta-carotene. However, no studies have explored whether the adverse effect of synthetic beta-carotene in cigarette smokers would also occur with natural beta-carotene supplementation. Until more is known, smokers should avoid all beta-carotene supplements and others should avoid synthetic beta-carotene.
In supplements, the natural form can be identified by the phrases “from D. salina,”“from an algal source,”“from a palm source,” or as “natural beta-carotene” on the label. The synthetic form is identified as “beta-carotene.”
How much is usually taken?
The most common beta-carotene supplement intake is probably 25,000 IU (15 mg) per day, though some people take as much as 100,000 IU (60 mg) per day. Whether the average person would benefit from supplementation with beta-carotene remains unclear.
Are there any side effects or interactions?
Beta-carotene supplementation, even in very large amounts, is not known to cause any serious side effects,16 17 however, excessive intake (more than 100,000 IU, or 60 mg per day) sometimes gives the skin a yellow-orange hue. People taking beta-carotene for long periods of time should also supplement with vitamin E, as beta-carotene may reduce vitamin E levels.18 Beta carotene supplementation may also decrease blood levels of lutein, another carotenoid.19
Warning: Synthetic beta-carotene has now been linked to increased risk of lung cancer in smokers. Until more is known, smokers should avoid all beta-carotene supplements.
Preliminary studies in animals indicate that beta-carotene supplementation, when combined with heavy alcohol consumption, may enhance liver toxicity.20 Until more is known, alcoholics and persons who consume alcohol on a daily basis should avoid supplementing with beta-carotene.
One study showed a slightly increased risk of vascular surgery among people with intermittent claudication who took beta-carotene supplements.21 Until more is known, persons wishing to use beta-carotene supplements should first consult with their doctor.
Are there any drug interactions?
Certain medicines may interact with beta-carotene. Refer to drug interactions for a list of those medicines.
References
1. Polidori MC, Mecocci P, Stahl W, et al. Plasma levels of lipophilic antioxidants in very old patients with type 2 diabetes. Diabetes Metab Res Rev 2000;16:15–9.
2. Shekelle RB, Lepper M, Liu S, et al. Dietary vitamin A and risk of cancer in the Western Electric Study. Lancet 1981;2:1185–90.
3. Hennekens CH, Burning 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.
4. Albanes D, Heinone OP, Taylor PR, et al. Alpha-tocopherol and beta-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.
5. 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.
6. 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;91:2102–6.
7. Törnwall 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;147:193–7.
8. Wang XD, Liu C, Bronson RT, et al. Retinoid signaling and activator protein-1 expression in ferrets given ß-carotene supplements and exposed to tobacco smoke. J Natl Cancer Inst 1999;91:60–6.
9. You CS, Parker RS, Goodman KJ, et al. Evidence of cis-trans isomerization of 9-cis-beta-carotene during absorption in humans. Am J Clin Nutr 1996;64:177–83.
10. Tamai H, Morinobu T, Murata T, et al. 9-cis beta-carotene in human plasma and blood cells after ingestion of beta-carotene. Lipids 1995;30:493–8.
11. Ben-Amotz A, Levy Y. Bioavailability of a natural isomer mixture compared with synthetic all-trans beta-carotene in human serum. Am J Clin Nutr 1996;63:729–34.
12. Bitterman N, Melamed Y, Ben-Amotz A. Beta-carotene and CNS oxygen toxicity in rats. J Appl Physiol 1994;76:1073–6.
13. Ben-Amotz A, Levy Y. Bioavailability of a natural isomer mixture compared with synthetic all-trans beta-carotene in human serum. Am J Clin Nutr 1996;63:729–34.
14. Yeum KJ, Azhu S, Xiao S, et al. Beta-carotene intervention trial in premalignant gastric lesions. J Am Coll Nutr 1995;14:536 [abstr #48].
15. Neuman I, Nahum H, Ben-Amotz A. Prevention of exercise-induced asthma by a natural isomer mixture of beta-carotene. Ann Allergy Asthma Immunol 1999;82:549–53.
16. Olson JA. Recommended dietary intakes (RDI) of vitamin A in humans. Am J Clin Nutr 1987;45:704–16.
17. Heywood R, Palmer AK, Gregson RL, Hummler H. The toxicity of beta-carotene. Toxicology 1985;36:91–100.
18. Xu MJ, Plezia PM, Alberts DS, et al. Reduction in plasma or skin alpha-tocopherol concentration with long-term oral administration of beta-carotene in humans and mice. J Natl Cancer Inst 1992;84:1559–65.
19. Gossage C, Deyhim M, Moser-Veillon PB, et al. Effect of beta-carotene supplementation and lactation on carotenoid metabolism and mitogenic T lymphocyte proliferation. Am J Clin Nutr 2000;71:950–5.
20. Leo MA, Lieber CS. Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr 1999;69:1071–85 [review].
21. Törnwall 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;147:193–7.
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