Beta-Carotene

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β-Carotene
Skeletal formula
Space-filling model
IUPAC name

beta,beta-Carotene

Systematic name

1,3,3-Trimethyl-2-[3,7,12,16-tetramethyl-18-(2,6,6-trimethylcyclohex-1-en-1-yl)octadeca-1,3,5,7,9,11,13,15,17-nonaen-1-yl]cyclohex-1-ene

Other names

Betacarotene
β-Carotene[1]
Food Orange 5
1,1'-(3,7,12,16-Tetramethyl-1,3,5,7,9,11,13,15,17-octadecanonaene-1,18-diyl)bis[2,6,6-trimethylcyclohexene]

Identifiers
CAS number 7235-40-7 YesY
PubChem 5280489
ChemSpider 4444129 YesY
UNII 01YAE03M7J YesY
ChEBI CHEBI:17579 YesY
ChEMBL CHEMBL1293 YesY
ATC code A11CA02,D02BB01
Jmol-3D images Image 1
Properties
Molecular formula C40H56
Molar mass 536.87 g mol−1
Appearance Dark orange crystals
Density 0.94 g/cm3
Melting point 180 to 182 °C; 356 to 360 °F; 453 to 455 K
Boiling point 633 to 677 °C; 1,171 to 1,251 °F; 906 to 950 K (at 760 Torr[1])
log P 14.764
Hazards
NFPA 704
1
0
0
Flash point 103 °C[2]
 N (verify) (what is: YesY/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
Infobox references

β-Carotene is a strongly colored red-orange pigment abundant in plants and fruits. It is an organic compound and chemically is classified as a hydrocarbon and specifically as a terpenoid (isoprenoid), reflecting its derivation from isoprene units. β-Carotene is biosynthesized from geranylgeranyl pyrophosphate.[3] It is a member of the carotenes, which are tetraterpenes, synthesized biochemically from eight isoprene units and thus having 40 carbons. Among this general class of carotenes, β-carotene is distinguished by having beta-rings at both ends of the molecule. Absorption of β-carotene is enhanced if eaten with fats, as carotenes are fat soluble.

Carotene is the substance in carrots, pumpkins and sweet potatoes that colors them orange and is the most common form of carotene in plants. When used as a food coloring, it has the E number E160a.[4]p119 The structure was deduced by Karrer et al. in 1930.[5] In nature, β-carotene is a precursor (inactive form) to vitamin A via the action of beta-carotene 15,15'-monooxygenase.[3] Isolation of β-carotene from fruits abundant in carotenoids is commonly done using column chromatography. The separation of β-carotene from the mixture of other carotenoids is based on the polarity of a compound. β-Carotene is a non-polar compound, so it is separated with a non-polar solvent such as hexane.[6] Being highly conjugated, it is deeply colored, and as a hydrocarbon lacking functional groups, it is very lipophilic.

Provitamin A activity

Plant carotenoids are the primary dietary source of provitamin A worldwide, with β-carotene as the most well-known provitamin A carotenoid. Others include α-carotene and β-cryptoxanthin. Carotenoid absorption is restricted to the duodenum of the small intestine and dependent on Class B scavenger receptor (SR-B1) membrane protein, which are also responsible for the absorption of vitamin E (α-tocopherol).[7] One molecule of β-carotene can be cleaved by the intestinal enzyme β,β-carotene 15,15'-monooxygenase into two molecules of vitamin A.[8]

Absorption efficiency is estimated to be between 9–22%. The absorption and conversion of carotenoids may depend on the form that the β-carotene is in (e.g., cooked vs. raw vegetables, or in a supplement), the intake of fats and oils at the same time, and the current stores of vitamin A and β-carotene in the body. Researchers list the following factors that determine the provitamin A activity of carotenoids:[9]

  • Species of carotene
  • Molecular linkage
  • Amount in the meal
  • Matrix properties
  • Effectors
  • Nutrient status
  • Genetics
  • Host specificity
  • Interactions between factors

Symmetric and asymmetric cleavage

In the molecule chain between the two cyclohexyl rings β-carotene cleaves either symmetrically or asymmetrically. Symmetric cleavage with the enzyme β,β-carotene-15,15'-dioxygenase requires the antioxidant α-tocopherol.[10] This symmetric cleavage gives two equivalent retinal molecules and each retinal molecule further reacts to give retinol (vitamin A) and retinoic acid. β-Carotene is also asymmetrically cleaved into two asymmetric products. The product of asymmetric cleavage is β-apocarotenal (8',10',12'). Asymmetric cleavage reduces the level of retinoic acid significantly.[11]

Conversion factors

Since 2001, the US Institute of Medicine uses retinol activity equivalents (RAE) for their Dietary Reference Intakes, defined as follows:[12]

Retinol Activity Equivalents (RAEs)

1 µg RAE = 1 µg retinol

1 µg RAE = 2 µg all-trans-β-carotene from supplements

1 µg RAE = 12 µg of all-trans-β-carotene from food

1 µg RAE = 24 µg α-carotene or β-cryptoxanthin from food

RAE takes into account carotenoids' variable absorption and conversion to vitamin A by humans better than and replaces the older retinol equivalent (RE) (1 µg RE = 1 µg retinol, 6 µg β-carotene, or 12 µg α-carotene or β-cryptoxanthin).[12] RE was developed 1967 by the United Nations/World Health Organization Food and Agriculture Organization (FAO/WHO).[13]

Another older unit of vitamin A activity is the international unit (IU). Like RE, IU doesn't take into account carotenoids' variable absorption and conversion to vitamin A by humans as well as the more modern RAE. Unfortunately, food and supplement labels still generally use IU, but IU can be converted to the more useful RAE as follows:[12]

International Units

1 µg RAE = 3.33 IU retinol

1 IU retinol = 0.3 μg RAE

1 IU β-carotene from supplements = 0.15 μg RAE

1 IU β-carotene from food = 0.05 μg RAE

1 IU α-carotene or β-cryptoxanthin from food = 0.025 μg RAE1

Sources in the diet

β-Carotene contributes to the orange color of many different fruits and vegetables. Vietnamese gac (Momordica cochinchinensis Spreng.) and crude palm oil are particularly rich sources, as are yellow and orange fruits, such as cantaloupe, mangoes and papayas, and orange root vegetables such as carrots and yams. The color of β-carotene is masked by chlorophyll in green leafy vegetables such as spinach, kale, sweet potato leaves, and sweet gourd leaves.[14] Vietnamese gac and crude palm oil have the highest content of β-carotene of any known plant source, 10 times higher than carrots, for example. However, gac is quite rare and unknown outside its native region of Southeast Asia, and crude palm oil is typically processed to remove the carotenoids before sale to improve the color and clarity.[15]

The average daily intake of β-carotene is in the range 2–7 mg, as estimated from a pooled analysis of 500,000 women living in the USA, Canada, and some European countries.[16]

The U.S. Department of Agriculture lists the following 10 foods to have the highest β-carotene content per serving.[17]

Item Grams per serving Serving size Milligrams β-carotene per serving Milligrams β-carotene per 100 g
Carrot juice, canned 236 1 cup 22.0 9.3
Pumpkin, canned, without salt 245 1 cup 17.0 6.9
Sweet potato, cooked, baked in skin, without salt 146 1 potato 16.8 11.5
Sweet potato, cooked, boiled, without skin 156 1 potato 14.7 9.4
Spinach, frozen, chopped or leaf, cooked, boiled, drained, without salt 190 1 cup 13.8 7.2
Carrots, cooked, boiled, drained, without salt 156 1 cup 13.0 8.3
Spinach, canned, drained solids 214 1 cup 12.6 5.9
Sweet potato, canned, vacuum pack 255 1 cup 12.2 4.8
Carrots, frozen, cooked, boiled, drained, without salt 146 1 cup 12.0 8.2
Collards, frozen, chopped, cooked, boiled, drained, without salt 170 1 cup 11.6 6.8

Side effects

The most common side effect of excessive β-carotene consumption is carotenodermia, a physically harmless condition that presents as a conspicuous orange skin tint arising from deposition of the carotenoid in the outermost layer of the epidermis.[18] Chronic, high doses of synthetic β-carotene supplements have been associated with a higher rate of lung cancer in smokers. Additionally, supplemental β-carotene may increase the risk of prostate cancer, intracerebral hemorrhage, and cardiovascular and total mortality in people who smoke cigarettes or have a history of high-level exposure to asbestos.[19] β-Carotene has a high tendency to oxidize,[20] more so than most food fats, and may thus to some extent hasten oxidation more than other food colors such as annatto.

Overdose

β-Carotene, a precursor form of vitamin A typical of vegetable sources such as carrots, is selectively converted into retinoids, so it does not cause hypervitaminosis A; however, overconsumption can cause carotenosis, a benign condition in which the skin turns orange.

The proportion of carotenoids absorbed decreases as dietary intake increases. Within the intestinal wall (mucosa), β-carotene is partially converted into vitamin A (retinol) by an enzyme, dioxygenase. This mechanism is regulated by the individual's vitamin A status. If the body has enough vitamin A, the conversion of β-carotene decreases. Therefore, β-carotene is a very safe source of vitamin A and high intakes will not lead to hypervitaminosis A. Excess β-carotene is predominantly stored in the fat tissues of the body. The adult's fat stores are often yellow from accumulated carotene while the infant's fat stores are white. Excessive intake of β-carotene leads to yellowish skin, but this is quickly reversible upon cessation of intake.[21]

Drug interactions

β-Carotene can interact with medication used for lowering cholesterol. Taking them together can lower the effectiveness of these medications and is considered only a moderate interaction.[22] β-Carotene should not be taken with Orlistat, a weight loss medication, as Orlistat can reduce the consumption of β-carotene by as much as 30%.[23] Bile acid sequestrants and proton-pump inhibitors can also decrease absorption of β-carotene.[24] Consuming alcohol with β-carotene can decrease its ability to convert to retinol and could possibly result in hepatotoxicity.[25]

β-Carotene and lung cancer in smokers

Chronic high doses of β-carotene supplementation increases the probability of lung cancer in cigarette smokers.[26] The effect is specific to supplementation dose as no lung damage has been detected in those who are exposed to cigarette smoke and who ingest a physiologic dose of β-carotene (6 mg), in contrast to high pharmacologic dose (30 mg). Therefore, the oncology from β-carotene is based on both cigarette smoke and high daily doses of β-carotene.[27] There have been at least two suggestions for the mechanism for the observed harmful effect of high-dose β-carotene supplementation in this group. None has so-far gained wide acceptance.

A common explanation of the high dose effect is that when retinoic acid is liganded to RAR-β (retinoic acid receptor beta), the complex binds AP1 (activator protein 1). AP1 is a transcription factor that binds to DNA and in downstream events promotes cell proliferation. Therefore, in the presence of retinoic acid, the retinoic acid:RAR-β complex binds to AP1 and inhibits AP-1 from binding to DNA. In that case, AP1 is no longer expressed, and cell proliferation does not occur. Cigarette smoke increases the asymmetric cleavage of β-carotene, decreasing the level of retinoic acid significantly. This can lead to a higher level of cell proliferation in smokers, and consequently, a higher probability of lung cancer.

Another β-carotene breakdown product suspected of causing cancer at high dose is trans-β-apo-8'-carotenal (common apocarotenal), which has been found in one study to be mutagenic and genotoxic in cell cultures which do not respond to β-carotene itself.[28]

Medical uses

β-Carotene has been used to treat various disorders such as erythropoietic protoporphyria. It has also been used to reduce the risk of breast cancer in women before menopause, and the risk of age-related macular degeneration (AMD).[29]

Cancer

It is debated whether β-carotene is effective in treating different forms of cancer and it has not currently been proven to prevent cancer in humans.[30] Studies have shown that patients with cervical intraepithelial neoplasia (CIN) respond favorably to β-carotene supplementation;[31] however, high levels of β-carotene have also been found to increase the risk of lung cancer in current and former smokers.[30] β-Carotene is used to help prevent breast cancer although there are currently no findings to support that diets high in β-carotene are associated with lower breast cancer risk.[32]

Compendial status

See also

References

  1. ↑ 1.0 1.1 "SciFinder - CAS Registry Number 7235-40-7". Retrieved Oct 21, 2009. 
  2. ↑ "22040 β-Carotene BioChemika, purum, ≥97.0% (UV)". Retrieved Oct 21, 2009. 
  3. ↑ 3.0 3.1 Susan D. Van Arnum (1998). "Vitamin A". Vitamin A in Kirk-Othmer Encyclopedia of Chemical Technology (45). New York: John Wiley. pp. 99–107. doi:10.1002/0471238961.2209200101181421.a01. ISBN 0-471-23896-1. 
  4. ↑ Milne, George W. A. (2005). Gardner's commercially important chemicals: synonyms, trade names, and properties. New York: Wiley-Interscience. ISBN 0-471-73518-3. 
  5. ↑ P. Karrer, A. Helfenstein, H. Wehrli, A. Wettstein (1930). "Pflanzenfarbstoffe XXV. Über die Konstitution des Lycopins und Carotins". Helvetica Chimica Acta 13 (5): 1084–1099. doi:10.1002/hlca.19300130532. 
  6. ↑ Mercadante, A.Z., Steck, A., Pfander, H. (1999). "Carotenoids from Guava (Psidium guajava L.): Isolation and Structure Elucidation". J. Agric. Food Chem. 47 (1): 145–151. doi:10.1021/jf980405r. PMID 10563863. 
  7. ↑ van Bennekum, A; Werder, Moritz; Thuahnai, Stephen T.; Han, Chang-Hoon; Duong, Phu; Williams, David L.; Wettstein, Philipp; Schulthess, Georg; Phillips, Michael C. (2005). "Class B scavenger receptor-mediated intestinal absorption of dietary β-carotene and cholesterol". Biochemistry. 44 (11): 4517–25. doi:10.1021/bi0484320. PMID 15766282. 
  8. ↑ Biesalski, HK; Chichili GR, Frank J, von Lintig J, Nohr D. (2007). "Conversion of β-carotene to retinal pigment". Vitamins and hormones. Vitamins & Hormones 75: 117–30. doi:10.1016/S0083-6729(06)75005-1. ISBN 978-0-12-709875-3. PMID 17368314. 
  9. ↑ Tanumihardjo, SA (2002). "Factors influencing the conversion of carotenoids to retinol: bioavailability to bioconversion to bioefficacy". Int J Vit Nutr Res 72 (1): 40–5. doi:10.1024/0300-9831.72.1.40. PMID 11887751. 
  10. ↑ Lakshman, MR (2004). "Alpha and omega of carotenoid cleavage". J Nutr. 134 (2): 241S–245S. PMID 14704327. 
  11. ↑ Kiefer, C., Hessel, S., Lampert, S.M., Vogt, K., Lederer, M.O., Breithaupt, D.E., von Lintig, J. (2001). "Identification and Characterization of a Mammalian Enzyme Catalyzing the Asymmetric Oxidative Cleavage of Provitamin A". The Journal of Biological Chemistry 276 (17): 14110–14116. doi:10.1074/jbc.M011510200 (inactive 2014-02-02). PMID 11278918. 
  12. ↑ 12.0 12.1 12.2 Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium and Zinc. (free download): National Academy Press. 2001. 
  13. ↑ Food and Agriculture Organization/World Health Organization (1967). Requirement of Vitamin A, Thiamine, Riboflavin and Niacin. FAO Food and Nutrition Series B. Rome. 
  14. ↑ Kidmose, U; Edelenbos M, Christensen LP, Hegelund E. (2005). "Chromatographic determination of changes in pigments in spinach (Spinacia oleracea L.) during processing.". J Chromatogr Sci. 46 (9): 466–72. PMID 16212792. 
  15. ↑ A.N. Mustapa, Z.A. Manan, C.Y. Mohd Azizi, W.B. Setianto, A.K. Mohd Omar, (2011) Extraction of b-carotenes from palm oil mesocarp using sub-critical R134a. Food Chemistry, 125, 262-267.
  16. ↑ Koushik, A.; Hunter DJ, Spiegelman D, Anderson KE, Buring JE, Freudenheim JL, Goldbohm RA, Hankinson SE, Larsson SC, Leitzmann M, Marshall JR, McCullough ML, Miller AB, Rodriguez C, Rohan TE, Ross JA, Schatzkin A, Schouten LJ, Willett WC, Wolk A, Zhang SM, Smith-Warner SA. (2006). "Intake of the major carotenoids and the risk of epithelial ovarian cancer in a pooled analysis of 10 cohort studies". Int J Cancer 119 (9): 2148–54. doi:10.1002/ijc.22076. PMID 16823847. 
  17. ↑ "USDA National Nutrient Database for Standard Reference, Release 21". Retrieved 2009-07-24. 
  18. ↑ Stahl W; Heinrich U; Jungmann H et al. (1998). "Increased Dermal Carotenoid Levels Assessed by Noninvasive Reflection Spectrophotometry Correlate with Serum Levels in Women Ingesting Betatene". Journal of Nutrition 128 (5): 903–7. PMID 9567001. 
  19. ↑ Beta-carotene, MedlinePlus
  20. ↑ Hurst, J. S.; Saini, M. K.; Jin, G. F.; Awasthi, Y. C.; Van Kuijk, F. J. G. M. (2005). "Toxicity of oxidized β-carotene to cultured human cells". Experimental Eye Research 81 (2): 239–243. doi:10.1016/j.exer.2005.04.002. PMID 15967438. 
  21. ↑ "Beta-carotene". DSM. 
  22. ↑ Web MD. "Beta-Carotene Interactions". Retrieved 28 May 2012. 
  23. ↑ University of Maryland Medical Center. "Possible Interactions with Beta-Carotene". Retrieved 29 May 2012. 
  24. ↑ Meschino Health. "Comprehensive Guide to Beta-Carotene". Retrieved 29 May 2012. 
  25. ↑ Leo, M. A.; Lieber, C. S. (1999). "Alcohol, vitamin A, and beta-carotene: Adverse interactions, including hepatotoxicity and carcinogenicity". The American journal of clinical nutrition 69 (6): 1071–1085. PMID 10357725. 
  26. ↑ Tanvetyanon T, Bepler G (July 2008). "Beta-carotene in multivitamins and the possible risk of lung cancer among smokers versus former smokers: a meta-analysis and evaluation of national brands". Cancer 113 (1): 150–7. doi:10.1002/cncr.23527. PMID 18429004. 
  27. ↑ Russel, R.M. (2002). "Beta-carotene and lung cancer". Pure Appl. Chem. 74 (8): 1461–1467. doi:10.1351/pac200274081461. 
  28. ↑ Alija AJ, Bresgen N, Sommerburg O, Siems W, Eckl PM (2004). "Cytotoxic and genotoxic effects of β-carotene breakdown products on primary rat hepatocytes". Carcinogenesis 25 (5): 827–31. doi:10.1093/carcin/bgh056. PMID 14688018. 
  29. ↑ WebMD. "Find a Vitamin or Supplement – Beta Carotene". Retrieved 29 May 2012. 
  30. ↑ 30.0 30.1 "Vitamin A, Retinoids, and Provitamin A Carotenoids". American Cancer Society. 
  31. ↑ Manetta, A.; Schubbert, T.; Chapman, J.; Schell, M. J.; Peng, Y. M.; Liao, S. Y.; Meyskens Jr, F. J. (1996). "Beta-Carotene treatment of cervical intraepithelial neoplasia: A phase II study". Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 5 (11): 929–932. PMID 8922303. 
  32. ↑ WebMD. "Beta-carotene intake and risk of postmenopausal breast cancer.". Retrieved 29 May 2012. 
  33. ↑ British Pharmacopoeia Commission Secretariat (2009). "Index, BP 2009". Retrieved 4 February 2010. 

External links

Carotenes (C40)
Xanthophylls (C40)
Apocarotenoids (C<40)
Vitamin A retinoids (C20)
Retinoid drugs
Fat soluble
Water soluble
Combinations

M: NUT

cof, enz, met

noco, nuvi, sysi/epon, met

drug (A8/11/12)

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