beta-Carotene

{{#if:Dark orange crystals0.94(6) g cm^-314.7641801825640|! style="background: #F8EABA; text-align: center;" colspan="2" | Properties

β-Carotene
File:Beta-Carotin.svg
File:Beta-Carotene-3D-spacefill.png
IUPAC name beta,beta-Carotene
Other names Betacarotene β-Carotene 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 7pxY
PubChem	573
ChemSpider	4444129 7pxY
UNII	01YAE03M7J 7pxY
ChEBI	CHEBI:17579 7pxY
ChEMBL	CHEMBL1293 7pxY
ATC code	A11CA02,D02BB01
Jmol-3D images	Image 1
SMILES CC(C=CC=C(C)C=CC1=C(C)CCCC1(C)C) =CC=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C <p><p style="word-wrap: break-word;">
InChI InChI=1S/C40H56/c1-31(19-13-21-33(3)25-27-37-35(5)23-15-29-39(37,7)8) 17-11-12-18-32(2)20-14-22-34(4)26-28-38-36(6)24-16-30-40(38,9) 10/h11-14,17-22,25-28H,15-16,23-24,29-30H2,1-10H3 7pxN Key: OENHQHLEOONYIE-UHFFFAOYSA-N 7pxN
Molecular formula	C40H56
Molar mass	536.87 g mol−1
Hazards
Flash point	103 °C
14pxN (verify) (what is: 10pxY/10pxN?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

β-Carotene is a strongly-coloured 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. 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 that colours them orange and is the most common form of carotene in plants. When used as a food colouring, it has the E number E160a.^p119 The structure was deduced by Karrer et al. in 1930. In nature, β-carotene is a precursor (inactive form) to vitamin A via the action of beta-carotene 15,15'-monooxygenase. 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. 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 (alpha-tocopherol). One molecule of β-carotene can be cleaved by the intestinal enzyme beta,beta-carotene 15,15'-monooxygenase into two molecules of vitamin A.

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 (cooked vs. raw vegetables, in a supplement), intake of fats and oils at the same time, and current stores of vitamin A and β-carotene in the body. Researchers list the following factors that determine the provitamin A activity of carotenoids:

• Species of carotenoid
• 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 beta,beta-carotene-15,15'-dioxygenase requires the antioxidant alpha-tocopherol. This symmetric cleavage gives two equivalent retinal molecules and each retinal molecule further reacts to give retinol (vitamin A) and retinoic acid. Beta-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.

Conversion factors

Until recently, vitamin A activity in foods was expressed as international units (IU). This is still the measurement generally used on food and supplement labels. However, it is difficult to calculate the total vitamin A activity in the diet in terms of IU, because both the absorption and conversion of carotenoids, as compared with retinol, are variable. The unit retinol equivalent (RE) was developed by the Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO) in 1967. More recently in 2001, the US Institute of Medicine proposed retinol activity equivalents (RAE) for their Dietary Reference Intakes.

International Units

1 RE = 3.33 IU vitamin A activity from retinol

1 RE = 10 IU vitamin A activity from β-carotene

(In Canada, Health Canada sets 1 RE = 6.667 IU from β-carotene.)

Retinol Equivalents (REs)

1 RE = 1 µg retinol

1 RE = 6 µg β-carotene (In Canada, Heath Canada sets 1 RE = 2 µg β-carotene.)

1 RE = 12 µg other provitamin A carotenoids

Retinol Activity Equivalents (RAEs)

1 RAE = 1 µg retinol

1 RAE = 2 µg all-trans-β-carotene as a supplement

1 RAE = 12 µg of all-trans-β-carotene in a food matrix

1 RAE = 24 µg other provitamin A carotenes in a food matrix

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, orange root vegetables such as carrots and yams and in green leafy vegetables such as spinach, kale, sweet potato leaves, and sweet gourd leaves. Vietnamese gac and crude palm oil have by far the highest content of β-carotene of any known fruit or vegetable, 10 times higher than carrots for example. However, gac is quite rare and unknown outside its native region of SE Asia, and crude palm oil is typically processed to remove the cartenoids before sale to improve the color and clarity.

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.

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

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. Chronic, high doses of synthetic β-carotene supplements have been associated with increased rate of lung cancer among those who smoke. 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. β-Carotene has a high tendency to oxidize, more so than most food fats, and may thus to some extent hasten oxidation more than other food colours 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.

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. β-Caroteneshould not be taken with Orlistat, a weight loss medication, as Orlistat can reduce the consumption of β-Caroteneby as much as 30%. Bile acid sequestrants and Proton-pump inhibitors can also decrease absorption of β-Carotene. Consuming alcohol with β-Carotene can decrease its ability to convert to retinol and could possibly result in hepatotoxicity.

β-Carotene and lung cancer in smokers

Chronic high doses of β-carotene supplementation increases the probability of lung cancer in cigarette smokers according to a study, although the validity of this statement has been put into question. 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. 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-beta (retinoic acid receptor beta), the complex binds AP1 (activator protein 1). AP1 is a transcription factor that binds to DNA and in downstream events promote cell proliferation. Therefore, in the presence of retinoic acid, the retinoic acid:RAR-beta complex binds to AP1 and inhibit 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.

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 as well as age-related macular degeneration (AMD).

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. Studies have shown that patients with cervical intraepithelial neoplasia (CIN) respond favorably to β-Carotene supplementation; however, high levels of β-Carotene have also been found to increase the risk of lung cancer in current and former smokers. 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.

Compendial status

• British Pharmacopoeia

See also

• Vitamin A
• Lycopene
• Lutein
• Zeaxanthin

External links

• USDA Webpage on β-carotene Content of Gac - Fatty Acids and Carotenoids in Gac (Momordica Cochinchinensis Spreng) Fruit.
• the beta-carotene project - Foods high in vitamin A or beta-carotene

cs:Beta-karoten