Beta-Carotene

Overview

Beta-carotene is part of a large family of compounds known as carotenoids (which includes over 600 members such as lycopene and lutein). Carotenoids are widely distributed in fruits and vegetables and are responsible, along with flavonoids, for contributing the color to many plants (a rule of thumb is the brighter the fruit/vegetable, then the higher the content of flavonoids and carotenoids). In terms of nutrition, beta-carotene’s primary role is as a precursor to vitamin A (the body can convert beta-carotene into vitamin A as it is needed). It is important to note that while beta-carotene and vitamin A are described together in many nutrition texts, they are not the same compound and they have vastly different effects in the body. Although beta-carotene can be converted to vitamin A in the body, there are important differences in terms of action and safety between the two compounds. Beta-carotene, like most carotenoids, is also a powerful antioxidant – so it has been recommended to protect against a variety of diseases such as cancer, cataracts and heart disease. The best food sources are brightly colored fruits and veggies such as cantaloupe, apricots, carrots, red peppers, sweet potatoes and dark leafy greens.

Evidence from population studies suggests that mixed sources of carotenoids from foods (eating lots of fruits and veggies) can help protect against many forms of cancer and heart disease as well as slow the progression of eye diseases such as cataracts and macular degeneration. As an antioxidant, it is logical (perhaps) to assume that beta-carotene (which is the primary carotenoid in the diet), may be responsible for a significant portion of the observed beneficial health effects of carotenoid-rich diets – but it is not logical to then assume that high doses of isolated beta-carotene supplements will deliver the same anti-cancer and cardioprotective effects observed with diets high in fruits and vegetables.

Comments

Beta-carotene supplements are relatively inexpensive and widely available. There are synthetic and natural sources of beta-carotene supplements. The natural forms typically come from algae (Dunaliella salina), fungi (Blakeslea trispora) or palm oil. In terms of conversion to vitamin A, the “trans-” form of beta-carotene has the maximum conversion rate. Synthetic beta-carotene is nearly all in the trans form (98%), while natural forms vary in the form of beta-carotene that they provide (the different forms are known as isomers). Among natural forms of beta-carotene, the fungal form provides the highest concentration of trans beta-carotene (94%) followed by algae sources (64%) and palm oil sources (34%) – so from the perspective of vitamin A conversion, either the synthetic form or the fungal form of beta-carotene will provide the highest conversion into active vitamin A. From a “mixed” carotenoid perspective, however, beta-carotene derived from algae also provides the “cis-” isomer of beta-carotene (about 31%) as well as alpha-carotene (3-4%) and other carotenoids (1-2%). Beta-carotene derived from palm oil provides the most “balanced” mixture of carotenoid isomers (34% trans-beta, 27% cis-beta, 30% alpha and 9% other carotenoids) – but it also has the lowest vitamin A conversion (because it only provides 34% as the trans form).

Based on the current scientific evidence, beta-carotene supplements should be utilized/recommended primarily as a way to supply adequate levels of vitamin A for proper nutrition – and not for prevention of cancer, heart disease or eye problems (although a “dietary” level of mixed carotenoids of up to 10mg/day probably poses no significant health risk). There may also be some benefit in consuming beta-carotene supplements for skin protection (reduced risk of sunburn) – but this effect may be more pronounced when taken in conjunction with other antioxidants such as lycopene, lutein, selenium, and vitamins C and E.

Scientific Support

It is important to note that the vast majority of the scientific evidence for the health benefits of beta-carotene comes from studies that looked at food sources of beta-carotene (and other carotenoids, often referred to as “mixed” carotenoids) – not supplements. From population (epidemiological) studies, we know that a high consumption of fruits and vegetables is associated with a significant reduction in many diseases – especially several forms of cancer (lung, stomach, colon, breast, prostate, and bladder). Because the data suggested that the “active” components in a plant-based diet may be carotenoids, and because beta-carotene is the chief carotenoid in our diets, it was widely believed (until about the mid-1990’s) that the majority of the health benefits attributable to fruits and vegetables may be due to beta-carotene.

One of the largest epidemiological studies, the Physicians’ Health Study (PHS - over 22,000 male physicians) found that while high levels of carotenoids obtained from the diet were associated with reduced cancer risk, beta-carotene from supplements (about 25mg/day) had no effect on cancer risk (Comstock et al. 1997). A possible explanation for this finding may be that while purified beta-carotene may contribute some antioxidant benefits, a “blend” of carotenoids (and/or other compounds in fruits and veggies) is probably even more important for preventing cancer. It may even be possible that isolated beta-carotene supplements could interfere with absorption or metabolism of other beneficial carotenoids from the diet.

Unfortunately, intervention studies that have looked at purified beta-carotene supplements (not mixed carotenoids) have not cleared up any of the confusion. In 1994, the results from a large (almost 30,000 subjects) supplementation study (ATBC – the Alpha-Tocopherol and Beta-Carotene study) showed not only that beta-carotene supplements (20mg/day for 5-8 years) did not prevent lung cancer in high risk subjects (long-time male smokers), but actually caused an increase in lung cancer risk by almost 20% (Pietinen et al. 1997). This same study also found a 10% increase in heart disease and a 20% increase in strokes among the beta-carotene users. In 1996, another large study (CARET – the Beta-Carotene and Retinol Efficacy Trial) found virtually the same thing – with subjects receiving beta-carotene showing almost 50% more cases of lung cancer (Goodman et al. 1996). These results were so alarming that the National Cancer Institute decided to halt the $40 million study nearly 2 years early. The ATBC study examined long-time heavy smokers, while the CARET study looked at present and former smokers as well as workers exposed to asbestos – all of which can be considered “high-risk” populations for developing lung cancer (which may or may not have contributed to the surprising study results).

On the positive side, beta-carotene has been successfully used for nearly 20 years to treat photosensitivity diseases, such as erythropoietic protoporphyria (EPP) and other skin conditions (Malvy et al. 2001). As such, beta-carotene has found its way into a variety of topical and internally consumed products meant for skin protection. In Europe, one of the most popular uses for carotenoid supplements (primarily beta-carotene and lycopene) is for skin protection during the summer sunbathing months (for “inside-out” sun protection).

Overall, it is interesting to note that of the 3 large-scale clinical trials on beta-carotene supplementation and cancer risk (ATBC, CARET and PHS), all 3 concluded that beta-carotene provided no protection against lung cancer – while 2 of them found a higher risk for lung cancer. However, the association between eating a diet high in fruits and vegetables and a reduced risk for cancer and heart disease remains strong – and there is no current evidence that small amounts of supplemental beta-carotene (such as a multivitamin) is unsafe. A prudent approach to carotenoid supplementation for disease prevention may be to strive to obtain a balanced blend of mixed carotenoids from foods – while reserving purified beta-carotene supplements for skin protection and as a source of vitamin A (see dosage suggestions below).

Safety / Dosage

At recommended dosages, beta-carotene is thought to be quite safe – although at least two large studies have shown that high-dose beta-carotene (20-50mg/day) can increase the risk of heart disease and cancer in smokers. Other reported side effects from high dose beta-carotene supplements (100,000IU or 60mg per day) include nausea, diarrhea and a yellow/orange tinge to the skin (especially hands and feet), which fades at lower doses of beta-carotene. The safest way to get your beta-carotene and other carotenoids is from eating a wide variety of fruits and vegetables.

Beta-carotene (the “trans-“ form) can be converted to vitamin A (3mg of beta-carotene supplies 5,000IU of vitamin A). Although beta-carotene supplements are commonly available in doses of 25,000IU (15mg) per day, and many people consume as much as 100,000IU (60mg) per day, the current state of the scientific literature does not support doses of beta-carotene much higher than those levels recommended for supplying vitamin A precursors (about 5,000-10,000IU per day of beta-carotene = 3-6mg).

References

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2.Comstock GW, Alberg AJ, Huang HY, Wu K, Burke AE, Hoffman SC, Norkus EP, Gross M, Cutler RG, Morris JS, Spate VL, Helzlsouer KJ. The risk of developing lung cancer associated with antioxidants in the blood: ascorbic acid, carotenoids, alpha-tocopherol, selenium, and total peroxyl radical absorbing capacity. Cancer Epidemiol Biomarkers Prev. 1997 Nov;6(11):907-16.

3.Daviglus ML, Dyer AR, Persky V, Chavez N, Drum M, Goldberg J, Liu K, Morris DK, Shekelle RB, Stamler J. Dietary beta-carotene, vitamin C, and risk of prostate cancer: results from the Western Electric Study. Epidemiology. 1996 Sep;7(5):472-7.

4.Goodman GE, Thornquist M, Kestin M, Metch B, Anderson G, Omenn GS. The association between participant characteristics and serum concentrations of beta-carotene, retinol, retinyl palmitate, and alpha-tocopherol among participants in the Carotene and Retinol Efficacy Trial (CARET) for prevention of lung cancer. Cancer Epidemiol Biomarkers Prev. 1996 Oct;5(10):815-21.

5.Hininger IA, Meyer-Wenger A, Moser U, Wright A, Southon S, Thurnham D, Chopra M, Van Den Berg H, Olmedilla B, Favier AE, Roussel AM. No significant effects of lutein, lycopene or beta-carotene supplementation on biological markers of oxidative stress and LDL oxidizability in healthy adult subjects. J Am Coll Nutr. 2001 Jun;20(3):232-8.

6.Kiokias S, Gordon MH. Dietary supplementation with a natural carotenoid mixture decreases oxidative stress. Eur J Clin Nutr. 2003 Sep;57(9):1135-40.

7.Malila N, Virtamo J, Virtanen M, Pietinen P, Albanes D, Teppo L. Dietary and serum alpha-tocopherol, beta-carotene and retinol, and risk for colorectal cancer in male smokers. Eur J Clin Nutr. 2002 Jul;56(7):615-21.

8.Malvy DJ, Favier A, Faure H, Preziosi P, Galan P, Arnaud J, Roussel AM, Briancon S, Hercberg S. Effect of two years' supplementation with natural antioxidants on vitamin and trace element status biomarkers: preliminary data of the SU.VI.MAX study. Cancer Detect Prev. 2001;25(5):479-85.

9.Nelson JL, Bernstein PS, Schmidt MC, Von Tress MS, Askew EW. Dietary modification and moderate antioxidant supplementation differentially affect serum carotenoids, antioxidant levels and markers of oxidative stress in older humans. J Nutr. 2003 Oct;133(10):3117-23.

10.Paolini M, Abdel-Rahman SZ, Sapone A, Pedulli GF, Perocco P, Cantelli-Forti G, Legator MS. Beta-carotene: a cancer chemopreventive agent or a co-carcinogen? Mutat Res. 2003 Jun;543(3):195-200.

11.Pietinen P, Ascherio A, Korhonen P, Hartman AM, Willett WC, Albanes D, Virtamo J. Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Epidemiol. 1997 May 15;145(10):876-87.

12.Pryor WA, Stahl W, Rock CL. Beta carotene: from biochemistry to clinical trials. Nutr Rev. 2000 Feb;58(2 Pt 1):39-53.

13.Vainio H. Chemoprevention of cancer: lessons to be learned from beta-carotene trials. Toxicol Lett. 2000 Mar 15;112-113:513-7.

14.van Poppel G. Epidemiological evidence for beta-carotene in prevention of cancer and cardiovascular disease. Eur J Clin Nutr. 1996 Jul;50 Suppl 3:S57-61.

15.Woodall AA, Britton G, Jackson MJ. Dietary supplementation with carotenoids: effects on alpha-tocopherol levels and susceptibility of tissues to oxidative stress. Br J Nutr. 1996 Aug;76(2):307-17.

16.Woutersen RA, Wolterbeek AP, Appel MJ, van den Berg H, Goldbohm RA, Feron VJ. Safety evaluation of synthetic beta-carotene. Crit Rev Toxicol. 1999 Nov;29(6):515-42.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.