Beta-carotene

Overview

Beta-carotene is a member of the carotenoid family which are organic fat-soluble pigments (typically red, orange, and yellow) synthesized by plants, algae, and some bacteria that have beneficial actions when consumed as part of a normal diet. Beta-carotene (and other carotenes) have direct actions in living systems, but they can also be converted to vitamin A (retinol). It is estimated that around 50 percent of the vitamin A in a typical American’s diet comes from carotenoid conversion.

History of Use

Beta-carotene has been used for a variety of conditions including cancer and heart disease prevention, exercise-induced asthma, age-related macular degeneration, Alzheimer’s, depression, infertility, Parkinson’s disease, and many others. It has also been used in the inherited disease called erythropoietic protoporphyria (EPP), and to reduce the risk of sunburn.

Chemistry

When ingested, beta-carotene (along with alpha, and gamma-carotene) is cleaved into two active retinal (vitamin A) molecules through the action of the enzyme beta-carotene 15,15′-monooxygenase. Where high doses of retinal are associated with toxicity (called hypervitaminosis A), high dose beta-carotene does not.[1] Consuming beta-carotene avoids this toxicity, as the action of beta-carotene 15,15’-monooxygenase is regulated by the amount of circulating retinal.

Commercially available beta-carotene is produced from palm oil extract or through algae/fungal bioproduction.

Dosage

For erythropoietic protoporphyria (EPP): Dosage is associated with age:

  • 1 to 4 years old: 60-90 mg/day, divided dose
  • 5 to 8 years old: 90-120 mg/day, divided dose
  • 9 to 12 years old: 120-150 mg/day, divided dose
  • 13 to 16 years old: 150-180 mg/day, divided dose
  • 16 and older: 180-300 mg/day, divided dose

Age-related macular degeneration (AMD): as part of a combination of supplemental vitamin C (500 mg), vitamin E (400 IU), beta-carotene (15 mg), zinc oxide (80 mg), and cupric oxide (2 mg) daily

Research Review

Beta-carotene is most effective as an overall antioxidant and as a precursor to vitamin A. It has also been used in erythropoietic protoporphyria (EPP), for age-related macular degeneration and has some preliminary use as a general sun-protectant, a cancer preventative, in exercise-induced asthma, and maintenance of cognitive functioning.

Age-Related Macular Degeneration

A large (n= 3549), long-term (10 yeas) clinical trial using supplemental vitamin C (500 mg), vitamin E (400 IU), beta-carotene (15 mg), zinc oxide (80 mg), and cupric oxide (2 mg) daily versus placebo has shown a dramatic 40 percent reduction in the risk of developing neovascular age-related macular degeneration (NV AMD) and age-related macular degeneration (AMD) .[2]

Cancer Prevention

While epidemiological studies have consistently shown that a diet rich in beta-carotene containing foods, or high blood levels of beta-carotene, are associated with a reduced risk of several cancers (including breast, prostate), [3] studies using supplemental beta-carotene have not shown such an association.[4] The reasons for this are many and might include the type of beta-carotene used, dosing, and the length of the study. Future study hopefully will clarify the role of supplemental beta-carotene and its use in cancer prevention.

Cognitive Performance

Antioxidants, like beta-carotene, have long been thought to be protective of cognitive functioning. While the results are mixed, it appears that long-term supplementation appears to be of benefit for the maintenance of cognitive function.

  • When dietary patterns are assessed, high consumption of beta-carotene rich foods is associated with higher composite cognitive score following 13 years of study.[5] Other studies have shown an inverse relationship between beta-carotene intake and poor cognitive function[6] and protective effects of a high antioxidant diet, particularly beta-carotene, in people who are genetically susceptible to dementia (presence of APOE 4 allele). [7]
  • In a supplement study (50 mg, alternate days) there were statistically significant differences between placebo and supplementation group for cognitive functioning following a year of supplementation. [8]

Exercise-Induced Asthma

A small, preliminary trial, a little over half (53 percent) of participants were protected against exercise-induced asthma following supplementation with beta-carotene (64 milligrams per day for a week). What this study shows is the potential for using beta-carotene for exercise-induced asthma, but further trials need to be undertaken.[9]

Photo-Protection

Photo-protection for people without EPP has also been under investigation. Carotenoids and flavonoids have the potential, following ingestion, to be distributed throughout light-exposed tissues (skin, eye) where they provide photo-protection. In preliminary studies, beta-carotene (along with lycopene) was able to prevent ultra-violet-induced erythema following 12 weeks of dietary intervention suggesting that consumption of beta-carotene may invoke protection against harmful UV radiation. [10] When light strikes the skin, a photo-oxidative process occurs and scavenging of these reactive oxygen species is thought to be the mechanism underlying the action of beta-carotene. While not as high of a protection as sun screen, beta-carotene appears to offer some sun protection. [11]

Sun Sensitivity in EPP

Beta-carotene has long been the treatment of choice for the inherited disease erythropoietic protoporphyria (EPP), which presents with extreme photosensitivity marked by pain, inflammation, and itching following sun exposure. The carotenoid pigments appear to lessen photosensitivity caused by photosensitizers (porphyrins).[12]

Cautions

Smoking: A few major trials have suggested a link between high, long-term, beta-carotene supplementation and lung cancer in smokers,[13] this, despite the fact that most epidemiological studies show an inverse relationship between consuming beta-carotene foods and cancers. The reason for the association appears to be an increase in oxidative metabolites in smokers that lead to a destruction of retinoic acid (vitamin A), diminished retinoid signaling, and enhanced cell proliferation.[14] Of note, it appears that participants in these studies who had adverse effects were also more likely to have low circulating beta-carotene levels and the start of the studies, suggesting a low vegetable and fruit intake in general in these people.[15]

Medications: A combination supplement (containing beta-carotene, selenium, vitamin C and vitamin E may decrease the effectiveness of some cholesterol-lowering medications and niacin (Statins).[16]

References

[1] Grune T, Lietz G, Palou A, et al. Beta-carotene is an important vitamin A source for humans. J Nutr. 2010 Dec;140(12):2268S-2285S. PMID: 20980645.

[2] Chew EY, Clemons TE, Agrón E, et al. Long-term effects of vitamins Cand E, β-carotene, and zinc on age-related macular degeneration: AREDS report no.35. Ophthalmology. 2013 Aug;120(8):1604-11.e4. PMID: 23582353.

[3] 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. PMID: 8841775.

[4] Druesne-Pecollo N, Latino-Martel P, Norat T, et al. Beta-carotene supplementation and cancer risk: a systematic review and metaanalysis of randomized controlled trials. Int J Cancer. 2010 Jul 1;127(1):172-84. PMID: 19876916.

[5] Kesse-Guyot E, Andreeva VA, Ducros V, et al. Carotenoid-rich dietary patterns during midlife and subsequent cognitive function. Br J Nutr. 2014 Mar 14;111(5):915-23. PMID: 24073964.

[6] Jama JW, Launer LJ, Witteman JC, et al. Dietary antioxidants and cognitive function in a population-based sample of older persons. The Rotterdam Study. Am J Epidemiol. 1996 Aug 1;144(3):275-80. PMID: 8686696.

[7] Hu P, Bretsky P, Crimmins EM, Guralnik JM, Reuben DB, Seeman TE. Association between serum beta-carotene levels and decline of cognitive function in high-functioning older persons with or without apolipoprotein E 4 alleles: MacArthur studies of successful aging. J Gerontol A Biol Sci Med Sci. 2006 Jun;61(6):616-20. PMID: 16799145.

[8] Grodstein F, Kang JH, Glynn RJ, Cook NR, Gaziano JM. A randomized trial of beta carotene supplementation and cognitive function in men: the Physicians’ Health Study II. Arch Intern Med. 2007 Nov 12;167(20):2184-90. PMID: 17998490.

[9] 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 Jun;82(6):549-53. PMID: 10400482.

[10] Stahl W, Sies H. Carotenoids and flavonoids contribute to nutritional protection against skin damage from sunlight. Mol Biotechnol. 2007 Sep;37(1):26-30. PMID: 17914160.

[11] Stahl W, Sies H. β-Carotene and other carotenoids in protection from sunlight. Am J Clin Nutr. 2012 Nov;96(5):1179S-84S. PMID: 23053552.

[12] Mathews-Roth MM. Carotenoids in erythropoietic protoporphyria and other photosensitivity diseases. Ann N Y Acad Sci. 1993 Dec 31;691:127-38. PMID: 8129282.

[13] Goralczyk R. Beta-carotene and lung cancer in smokers: review of hypotheses and status of research. Nutr Cancer. 2009;61(6):767-74. PMID: 20155614.

[14] Russell RM. The enigma of beta-carotene in carcinogenesis: what can be learned from animal studies. J Nutr. 2004 Jan;134(1):262S-268S. PMID: 14704331.

[15] Albanes D. Beta-carotene and lung cancer: a case study. Am J Clin Nutr. 1999 Jun;69(6):1345S-1350S. PMID: 10359235.

[16] Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol. 2001 Aug;21(8):1320-6. PMID: 11498460.