Beta-Carotene

• How It Works

  Beta-carotene is not effective in treating heart disease, cancer, or HIV or preventing cataracts or macular degeneration.

  Beta-carotene is an antioxidant that is found in yellow and orange fruits, such as apricots, cantaloupe, and papaya, as well as squash, carrots, sweet potatoes, pumpkin, leafy greens, and broccoli. Although scientists have proposed a number of mechanisms by which beta-carotene obtained through a healthy diet may prevent cancer, current evidence does not support supplementation.

• Purported Uses
  • As an antioxidant
    Several studies support this use.
  • To prevent cancer
    Available evidence does not support the use of beta carotene supplements for preventing cancer. In fact, high beta-carotene intake has been linked to higher risk of lung cancer in male smokers and aggressive prostate cancer. (This does not necessarily apply to beta carotene obtained from the diet. Beta carotene may act in conjunction with other phytochemicals in fruits and vegetables).
  • To prevent and treat heart disease
    Several large and well-designed clinical trials and population studies show that taking beta-carotene supplements does not reduce the risk of myocardial infarction (heart attack), angina, or coronary artery disease. In fact, a review of clinical trials showed that beta-carotene was associated with a small increase in overall death as well as death to cardiovascular disease.
  • To prevent cataracts
    Clinical trials generally have shown that taking beta-carotene supplements does not reduce the risk of developing cataracts, but a small study found that amounts of beta-carotene in the blood were associated with decreased cataracts, indicating that beta-carotene obtained from the diet, but not supplements, may be helpful.
  • To treat HIV and AIDS
    Although small studies have suggested that beta-carotene supplements could increase CD4 cell counts, clinical trials have not been able to replicate these results.
  • To stimulate the immune system
    Some laboratory experiments show that beta-carotene stimulates certain aspects of the immune system, but it is not certain that this effect occurs in the human body.
  • To prevent and treat macular degeneration
    One clinical trial suggested that taking an antioxidant supplement plus zinc reduces the risk of macular degeneration, but it is not clear whether beta-carotene, or any of the other antioxidants in this supplement, were responsible for these effects.
  • To treat oral leukoplakia
    Several clinical trials have shown that beta-carotene supplementation can induce remission of oral leukoplakia, a pre-cancerous lesion in the mouth.
  • To treat type 2 diabetes
    Available data are conflicting.
  • To improve cognition
    Clinical findings suggest that long-term supplementation with beta-carotene may improve cognition.
• Side Effects

  Prolonged intake of high doses of beta-carotene can lead to carotenodermia, a harmless yellowish discoloration of the skin.

• Special Point

  High dietary intake of fruit and vegetables has been associated with reduced risk of cancer and heart disease. Although beta-carotene supplements do not appear to prevent or effectively treat either of these diseases, beta-carotene obtained from the diet may be beneficial. This is because it may interact with other phytochemicals in fruits and vegetables and have a greater effect on the body than do supplements.

• Clinical Summary

  A natural pigment synthesized by plants, beta-carotene is used as an antioxidant and an immunostimulant, and to prevent or treat cancer, HIV, heart disease, and leukoplakia. Beta-carotene, along with alpha-carotene and beta-cryptoxanthin, can be converted to retinol and is classified as a provitamin A carotenoid. Supplementation with beta-carotene does not increase overall vitamin A levels or lead to vitamin A toxicity. Animal studies show that beta-carotene promotes the development of pulmonary adenocarcinoma via increased cAMP signaling ⁽²⁹⁾.

  Available data of beta-carotene supplementation for HIV-positive patients and its effects on CD4 counts ⁽¹⁰⁾ as well as cardiovascular disease are conflicting. A meta-analysis demonstrated a small but significant increase in all-cause mortality and cardiovascular death for the beta-carotene arm over placebo ⁽¹¹⁾, whereas other studies reported no such effects ⁽³⁹⁾ or benefits of beta-carotene supplementation on cardiovascular disease ⁽¹²⁾ or its risk factors ⁽¹³⁾. Consistent associations between serum beta-carotene levels and risk of developing type 2 diabetes are lacking as well ^(14) (15). Additional studies have reported serum beta-carotene to be inversely associated with the incidence of cataract formation ⁽¹⁶⁾; higher intake of β-carotene (while avoiding vitamin C supplements) to be associated with lowered risk of acquired hearing loss in women ⁽⁴⁰⁾; long-term supplementation to increase cognitive function ⁽¹⁷⁾; and high dietary intake to have a protective effect on buccal cells from relative telomere length (RTL) shortening ⁽⁴¹⁾.

  Epidemiological associations between beta-carotene and cancer risk are conflicting. Whereas high dietary intake was associated with reduced risk of cervical cancer ⁽¹⁾, high serum levels were associated with increased risk for aggressive prostate cancer ⁽²⁾, but with reduced risk of aggressive urothelial cell carcinoma ⁽³²⁾. Findings of beta-carotene and chemoprevention are inconsistent as well. Consumption of beta carotene, vitamins A, C, fruits and vegetables did not influence the risk of renal cell carcinoma ⁽³¹⁾; supplementation with antioxidants, beta-carotene and vitamins A, C, and E, did not prevent gastrointestinal cancer, and beta-carotene may actually increase overall mortality ^(3) (4). Data from large, multi-center trials suggest that supplementation may not lower the risk of prostate cancer ^(5) (6), and in male smokers over the age 40, it may increase lung cancer incidence ^{(7) (30) (42)}.  When combined with cigarette smoking, beta-carotene supplements may also reduce the efficacy of cancer therapies, resulting in increased recurrence and mortality ⁽⁸⁾. A large-scale cohort study in the Netherlands suggests that alcohol consumption, too, has a negative effect on the chemopreventive property of beta-carotene ⁽⁹⁾.

  The U.S. Preventive Services Task Force (USPSTF) recommends against beta-carotene or vitamin E supplements for the prevention of cardiovascular disease or cancer ⁽³³⁾.

• Food Sources

  Deep yellow and orange fruits (apricots, cantaloupe, papaya), squash, carrots, sweet potatoes, pumpkin, leafy greens, and broccoli ^(18) (19)

• Purported Uses
  • Cancer prevention
  • Cardiovascular disease
  • Eye disorders
  • HIV and AIDS
  • Immunostimulation
  • Oral leukoplakia
• Mechanism of Action

  Beta-carotene has strong antioxidant effects. It protects lipid peroxidation and provitamin-A activity, thereby preventing oxidative damage ⁽³⁴⁾. It was also shown to alleviate the severity of ulcerative colitis in a murine model by modulating several molecular targets including nuclear factor-kappa B, cyclooxygenase-2, interleukin 17, and connective tissue growth factor ⁽³⁵⁾.

  In other studies, beta-carotene reduced cell growth and induced apoptosis in a variety of cancer cell lines through caveolin-1 expression ⁽²⁰⁾. In vivo studies suggest that it induces glutathione production ⁽²¹⁾. Beta-carotene may also enhance macrophage function and natural killer (NK) cell cytotoxicity, and increase T-helper lymphocyte counts. However, clinical findings suggest that beta-carotene can increase cancer risk. It was shown to induce angiogenic gene expression in human umbilical vein endothelial cells (HUVEC) as well as HUVEC migration ⁽²²⁾; and stimulate cellular proliferation in pancreatic ductal adenocarcinoma ⁽²³⁾ as well as in lung cancer cells ⁽²⁴⁾. More research is needed.

• Adverse Reactions

  Carotenodermia (yellowish, harmless discoloration of the skin) was reported following chronic intake of food and supplements containing large amounts of carotenoids ^{(36) (37) (38) (43)}.

• Herb-Drug Interactions

  Ethanol: Hepatotoxic effects of ethanol may be potentiated by high doses of beta-carotene. A large-scale cohort study in the Netherlands found that alcohol consumption has a negative effect on the chemopreventive activity of beta-carotene.

• References

  1. Ghosh C, Baker JA, Moysich KB, et al. Dietary intakes of selected nutrients and food groups and risk of cervical cancer. Nutr Cancer. May-Jun 2008;60(3):331-341.

  2. Peters U, Leitzmann MF, Chatterjee N, et al. Serum lycopene, other carotenoids, and prostate cancer risk: a nested case-control study in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev. May 2007;16(5):962-968.

  3. Bjelakovic G, Nikolova D, Simonetti RG, et al. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet. Oct 2-8 2004;364(9441):1219-1228.

  4. Bjelakovic G, Nikolova D, Simonetti RG, et al. Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database Syst Rev. 2008(3):CD004183.

  5. Kirsh VA, Hayes RB, Mayne ST, et al. Supplemental and dietary vitamin E, beta-carotene, and vitamin C intakes and prostate cancer risk. J Natl Cancer Inst. Feb 15 2006;98(4):245-254.

  6. Ambrosini GL, de Klerk NH, Fritschi L, et al. Fruit, vegetable, vitamin A intakes, and prostate cancer risk. Prostate Cancer Prostatic Dis. 2008;11(1):61-66.

  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. Apr 14 1994;330(15):1029-1035.

  8. Meyer F, Bairati I, Fortin A, et al. Interaction between antioxidant vitamin supplementation and cigarette smoking during radiation therapy in relation to long-term effects on recurrence and mortality: a randomized trial among head and neck cancer patients. Int J Cancer. Apr 1 2008;122(7):1679-1683.

  9. Leo MA, Lieber CS. Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr. Jun 1999;69(6):1071-1085.

  10. Coodley GO, Coodley MK, Lusk R, et al. Beta-carotene in HIV infection: an extended evaluation. AIDS. Aug 1996;10(9):967-973.

  11. Vivekananthan DP, Penn MS, Sapp SK, et al. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet. Jun 14 2003;361(9374):2017-2023.

  12. 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. May 2 1996;334(18):1145-1149.

  13. Wang L, Gaziano JM, Norkus EP, et al. Associations of plasma carotenoids with risk factors and biomarkers related to cardiovascular disease in middle-aged and older women. Am J Clin Nutr. Sep 2008;88(3):747-754.

  14. Arnlov J, Zethelius B, Riserus U, et al. Serum and dietary beta-carotene and alpha-tocopherol and incidence of type 2 diabetes mellitus in a community-based study of Swedish men: report from the Uppsala Longitudinal Study of Adult Men (ULSAM) study. Diabetologia. Nov 5 2008.

  15. Kataja-Tuomola M, Sundell JR, Mannisto S, et al. Effect of alpha-tocopherol and beta-carotene supplementation on the incidence of type 2 diabetes. Diabetologia. Jan 2008;51(1):47-53.

  16. Dherani M, Murthy GV, Gupta SK, et al. Blood levels of vitamin C, carotenoids and retinol are inversely associated with cataract in a North Indian population. Invest Ophthalmol Vis Sci. Aug 2008;49(8):3328-3335.

  17. Grodstein F, Kang JH, Glynn RJ, et al. A randomized trial of beta carotene supplementation and cognitive function in men: the Physicians’ Health Study II. Arch Intern Med. Nov 12 2007;167(20):2184-2190.

  18. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington D.C.: National Academy Press; 2000.

  19. Schuurman AG, Goldbohm RA, Brants HA, et al.A prospective cohort study on intake of retinol, vitamins C and E, and carotenoids and prostate cancer risk (Netherlands). Cancer Causes Control. Aug 2002;13(6):573-582.

  20. Palozza P, Sestito R, Picci N, et al. The sensitivity to beta-carotene growth-inhibitory and proapoptotic effects is regulated by caveolin-1 expression in human colon and prostate cancer cells. Carcinogenesis. Nov 2008;29(11):2153-2161.

  21. Takeda S, Bando N, Yamanishi R. Ingested beta-carotene enhances glutathione level and up-regulates the activity of cysteine cathepsin in murine splenocytes. Biosci Biotechnol Biochem. Jun 2008;72(6):1595-1600.

  22. Kiec-Wilk B, Polus A, Mikolajczyk M, et al. Beta-carotene and arachidonic acid induced DNA methylation and the regulation of pro-chemotactic activity of endothelial cells and its progenitors. J Physiol Pharmacol. Dec 2007;58(4):757-766.

  23. Al-Wadei HA, Majidi M, Tsao MS, et al. Low concentrations of beta-carotene stimulate the proliferation of human pancreatic duct epithelial cells in a PKA-dependent manner. Cancer Genomics Proteomics. Jan-Feb 2007;4(1):35-42.

  24. Al-Wadei HA, Takahashi T, Schuller HM. Growth stimulation of human pulmonary adenocarcinoma cells and small airway epithelial cells by beta-carotene via activation of cAMP, PKA, CREB and ERK1/2. Int J Cancer. Mar 15 2006;118(6):1370-1380.

  25. Zhang LX, Cooney RV, Bertram JS.Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/10T1/2 cells: relationship to their cancer chemopreventive action. Carcinogenesis. Nov 1991;12(11):2109-2114.

  26. Brody T. Nutritional Biochemistry. San Diego (CA): Academic Press; 1999.

  27. Nierenberg DW, Stukel TA, Baron JA, et al. Determinants of increase in plasma concentration of beta-carotene after chronic oral supplementation. The Skin Cancer Prevention Study Group. Am J Clin Nutr. Jun 1991;53(6):1443-1449.

  28. Pronsky ZM. Power’s and Moore’s Food-Medication Interactions. 11th ed. Pottstown (PA): Food Medication Interactions; 2000.

  29. Al-Wadei HA, Schuller HM. beta-Carotene promotes the development of NNK-induced small airway-derived lung adenocarcinoma. Eur J Cancer. 2009 May;45(7):1257-64.

  30. Satia JA, Littman A, Slatore CG, Galanko JA, White E. Long-term use of beta-carotene, retinol, lycopene, and lutein supplements and lung cancer risk: results from the VITamins And Lifestyle (VITAL) study. Am J Epidemiol. 2009 Apr 1;169(7):815-28.

  31. Bertoia M, Albanes D, Mayne ST, et al. No association between fruit, vegetables, antioxidant nutrients and risk of renal cell carcinoma. Int J Cancer. 2010 Mar 15;126(6):1504-12.

  32. Ros MM, Bueno-de-Mesquita HB, Kampman E, et al. Plasma carotenoids and vitamin C concentrations and risk of urothelial cell carcinoma in the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr. 2012 Oct;96(4):902-10.

  33. Moyer VA; U.S. Preventive Services Task Force. Vitamin, mineral, and multivitamin supplements for the primary prevention of cardiovascular disease and cancer: U.S. Preventive services Task Force recommendation statement. Ann Intern Med. 2014 Apr 15;160(8):558-64.

  34. Zhang PY, Xu X, Li XC. Cardiovascular diseases: oxidative damage and antioxidant protection. Eur Rev Med Pharmacol Sci. 2014 Oct;18(20):3091-6.

  35. Trivedi PP, Jena GB. Mechanistic insight into beta-carotene-mediated protection against ulcerative colitis-associated local and systemic damage in mice. Eur J Nutr. 2014 Jul 30. [Epub ahead of print]

  36. Boere IA, Hoskam JA. Yellow discolouration. Neth J Med. 2006 Feb;64(2):56-7.

  37. Sansone RA, Sansone LA. Carrot man: a case of excessive beta-carotene ingestion. Int J Eat Disord. 2012 Sep;45(6):816-8.

  38. Santos VM, Camilo AG, Souza LA, Souza DW, Marinho CS, Monteiro LM. A woman with treated breast cancer, recent neurological symptoms and xanthoderma. Acta Med Iran. 2013 Apr 6;51(3):195-8.

  39. Jenkins DJA, Spence JD, Giovannucci EL, et al. Supplemental Vitamins and Minerals for CVD Prevention and Treatment. J Am Coll Cardiol. 2018 Jun 5;71(22):2570-2584.

  40. Curhan SG, Stankovic KM, Eavey RD, Wang M, Stampfer MJ, Curhan GC. Carotenoids, vitamin A, vitamin C, vitamin E, and folate and risk of self-reported hearing loss in women. Am J Clin Nutr. 2015 Nov;102(5):1167-75.

  41. Yabuta S, Masaki M, Shidoji Y. Associations of Buccal Cell Telomere Length with Daily Intake of β-Carotene or α-Tocopherol Are Dependent on Carotenoid Metabolism-related Gene Polymorphisms in Healthy Japanese Adults. J Nutr Health Aging. 2016 Mar;20(3):267-74.

  42. Middha P, Weinstein SJ, Männistö S, Albanes D, Mondul AM. β-carotene Supplementation and Lung Cancer Incidence in the ATBC Study: the Role of Tar and Nicotine. Nicotine Tob Res. 2018 Jun 8. doi: 10.1093/ntr/nty115. [Epub ahead of print]

  43. Wang ZS, Liu XK, Li J. Woman With Yellow Palms and Soles. JAMA. 2017 Apr 18;317(15):1574-1575.