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β-Carotene
Skeletal formula
Ball-and-stick model
Space-filling model
Names
IUPAC name
β,β-Carotene
Systematic IUPAC name
1,1′-[(1E,3E,5E,7E,9E,11E,13E,15E,17E)-3,7,12,16-Tetramethyloctadeca-1,3,5,7,9,11,13,15,17-nonaene-1,18-diyl]bis(2,6,6-trimethylcyclohex-1-ene)
Other names
Betacarotene (INN), β-Carotene,[3] Food Orange 5, Provitamin A
Identifiers
3D model (JSmol)
1917416
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.027.851 Edit this at Wikidata
EC Number
  • 230-636-6
E number E160a (colours)
KEGG
UNII
  • 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 ☒N
    Key: OENHQHLEOONYIE-UHFFFAOYSA-N ☒N
  • CC2(C)CCCC(\C)=C2\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(/C)CCCC1(C)C
Properties
C40H56
Molar mass 536.888 g·mol−1
Appearance Dark orange crystals
Density 1.00 g/cm3[4]
Melting point 183 °C (361 °F; 456 K)[4]
decomposes[6]
Boiling point 654.7 °C (1,210.5 °F; 927.9 K)
at 760 mmHg (101324 Pa)
Insoluble
Solubility Soluble in CS2, benzene, CHCl3, ethanol
Insoluble in glycerin
Solubility in dichloromethane 4.51 g/kg (20 °C)[5] = 5.98 g/L (given BCM density of 1.3266 g/cm3 at 20°C)
Solubility in hexane 0.1 g/L
log P 14.764
Vapor pressure 2.71·10−16 mmHg
1.565
Pharmacology
A11CA02 (WHO) D02BB01 (WHO)
Hazards
GHS labelling:
GHS07: Exclamation mark
Warning
H315, H319, H412
P264, P273, P280, P302+P352, P305+P351+P338, P321, P332+P313, P337+P313, P362, P501
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 0: Exposure under fire conditions would offer no hazard beyond that of ordinary combustible material. E.g. sodium chlorideFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
0
1
0
Flash point 103 °C (217 °F; 376 K)[6]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

β-Carotene (beta-carotene) is an organic, strongly colored red-orange pigment abundant in fungi,[7] plants, and fruits. It is a member of the carotenes, which are terpenoids (isoprenoids), synthesized biochemically from eight isoprene units and thus having 40 carbons.

Dietary β-carotene is a provitamin compound, converting in the body to retinol (vitamin A).[8] In foods, it has rich content in carrots, pumpkin, spinach, and sweet potato.[8] It is used as a dietary supplement and may be prescribed to treat erythropoietic protoporphyria, an inherited condition of sunlight sensitivity.[9]

β-carotene is the most common carotenoid in plants.[8] When used as a food coloring, it has the E number E160a.[10]: 119  The structure was deduced in 1930.[11]

Isolation of β-carotene from fruits abundant in carotenoids is commonly done using column chromatography. It is industrially extracted from richer sources such as the algae Dunaliella salina.[12] 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.[13] Being highly conjugated, it is deeply colored, and as a hydrocarbon lacking functional groups, it is lipophilic.

Provitamin A activity

[edit]

Plant carotenoids are the primary dietary source of provitamin A worldwide, with β-carotene as the best-known provitamin A carotenoid.[8] Others include α-carotene and β-cryptoxanthin.[8] Carotenoid absorption is restricted to the duodenum of the small intestine. 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][14][15]

Absorption, metabolism and excretion

[edit]

As part of the digestive process, food-sourced carotenoids must be separated from plant cells and incorporated into lipid-containing micelles to be bioaccessible to intestinal enterocytes.[8] If already extracted (or synthetic) and then presented in an oil-filled dietary supplement capsule, there is greater bioavailability compared to that from foods.[16]

At the enterocyte cell wall, β-carotene is taken up by the membrane transporter protein scavenger receptor class B, type 1 (SCARB1). Absorbed β-carotene is then either incorporated as such into chylomicrons or first converted to retinal and then retinol, bound to retinol binding protein 2, before being incorporated into chylomicrons.[8] The conversion process consists of one molecule of β-carotene cleaved by the enzyme beta-carotene 15,15'-dioxygenase, which is encoded by the BCO1 gene, into two molecules of retinal.[8] When plasma retinol is in the normal range the gene expression for SCARB1 and BCO1 are suppressed, creating a feedback loop that suppresses β-carotene absorption and conversion.[16]

The majority of chylomicrons are taken up by the liver, then secreted into the blood repackaged into low density lipoproteins (LDLs).[8] From these circulating lipoproteins and the chylomicrons that bypassed the liver, β-carotene is taken into cells via receptor SCARB1. Human tissues differ in expression of SCARB1, and hence β-carotene content. Examples expressed as ng/g, wet weight: liver=479, lung=226, prostate=163 and skin=26.[16]

Once taken up by peripheral tissue cells, the major usage of absorbed β-carotene is as a precursor to retinal via symmetric cleavage by the enzyme beta-carotene 15,15'-dioxygenase, which is encoded by the BCO1 gene.[8] A lesser amount is metabolized by the mitochondrial enzyme beta-carotene 9',10'-dioxygenase, which is encoded by the BCO2 gene. The products of this asymmetric cleavage are two beta-ionone molecules and rosafluene. BCO2 appears to be involved in preventing excessive accumulation of carotenoids; a BCO2 defect in chickens results in yellow skin color due to accumulation in subcutaneous fat.[17][18]

Conversion factors

[edit]

For counting dietary vitamin A intake, β-carotene may be converted either using the newer retinol activity equivalents (RAE) or the older international unit (IU).[8]

Retinol activity equivalents (RAEs)

[edit]

Since 2001, the US Institute of Medicine uses retinol activity equivalents (RAE) for their Dietary Reference Intakes, defined as follows:[8][19]

  • 1 μg RAE = 1 μg retinol from food or supplements
  • 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).[19] RE was developed 1967 by the United Nations/World Health Organization Food and Agriculture Organization (FAO/WHO).[20]

International Units

[edit]

Another older unit of vitamin A activity is the international unit (IU).[8] Like retinol equivalent, the international unit does not take into account carotenoid variable absorption and conversion to vitamin A by humans, as well as the more modern retinol activity equivalent. Food and supplement labels still generally use IU, but IU can be converted to the more useful retinol activity equivalent as follows:[19]

  • 1 μg RAE = 3.33 IU retinol
  • 1 IU retinol = 0.3 μg RAE
  • 1 IU β-carotene from supplements = 0.3 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

Dietary sources

[edit]

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 US, Canada, and some European countries.[21] Beta-carotene is found in many foods and is sold as a dietary supplement.[8] 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, pumpkin, and papayas, and orange root vegetables such as carrots and sweet potatoes.[8]

The color of β-carotene is masked by chlorophyll in green leaf vegetables such as spinach, kale, sweet potato leaves, and sweet gourd leaves.[8][22]

The U.S. Department of Agriculture lists foods high in β-carotene content:[23]

Food Beta-carotene

Milligrams per 100 g

Sweet potato, skinned, boiled 9.4
Carrot juice 9.3
Carrots, raw or boiled 9.2
Kale, boiled 8.8
Pumpkin, canned 6.9
Spinach, canned 5.9

No dietary requirement

[edit]

Government and non-government organizations have not set a dietary requirement for β-carotene.[16]

Side effects

[edit]

Excess β-carotene is predominantly stored in the fat tissues of the body.[8] 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.[8][9][16][24]

Carotenosis

[edit]

Carotenoderma, also referred to as carotenemia, is a benign and reversible medical condition where an excess of dietary carotenoids results in orange discoloration of the outermost skin layer.[8] It is associated with a high blood β-carotene value. This can occur after a month or two of consumption of beta-carotene rich foods, such as carrots, carrot juice, tangerine juice, mangos, or in Africa, red palm oil. β-carotene dietary supplements can have the same effect. The discoloration extends to palms and soles of feet, but not to the white of the eye, which helps distinguish the condition from jaundice. Carotenodermia is reversible upon cessation of excessive intake.[25] Consumption of greater than 30 mg/day for a prolonged period has been confirmed as leading to carotenemia.[16][26]

No risk for hypervitaminosis A

[edit]

At the enterocyte cell wall, β-carotene is taken up by the membrane transporter protein scavenger receptor class B, type 1 (SCARB1). Absorbed β-carotene is then either incorporated as such into chylomicrons or first converted to retinal and then retinol, bound to retinol binding protein 2, before being incorporated into chylomicrons. The conversion process consists of one molecule of β-carotene cleaved by the enzyme beta-carotene 15,15'-dioxygenase, which is encoded by the BCO1 gene, into two molecules of retinal. When plasma retinol is in the normal range the gene expression for SCARB1 and BCO1 are suppressed, creating a feedback loop that suppresses absorption and conversion. Because of these two mechanisms, high intake will not lead to hypervitaminosis A.[16]

Drug interactions

[edit]

β-Carotene can interact with medication used for lowering cholesterol.[8] Taking them together can lower the effectiveness of these medications and is considered only a moderate interaction.[8] Bile acid sequestrants and proton-pump inhibitors can decrease absorption of β-carotene.[27] Consuming alcohol with β-carotene can decrease its ability to convert to retinol and could possibly result in hepatotoxicity.[28] Research on animal feeds, suggests that β-Carotene might act as an "antivitamin D" that counteracts the availability in forages of vitamin D.[29][30]

β-Carotene and lung cancer in smokers

[edit]

Chronic high doses of β-carotene supplementation increases the probability of lung cancer in smokers[8][31] while its natural vitamer, retinol, increases lung cancer in smokers and nonsmokers. 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 physiological dose of β-carotene (6 mg), in contrast to high pharmacological dose (30 mg).[8][32]

Increases in lung cancer have been attributed to the tendency of β-carotene to oxidize,[33] yet based on the pharmacokinetics of β-carotene absorption and transport through the intestine and the lack of specific β-carotene transporters, it is unlikely that β-carotene reaches the lung of smokers in sufficient quantities.[34] Additional research is required to understand the link between the increased risk of cancer and all-cause mortality following β-carotene supplementation.

Additionally, supplemental, high-dose β-carotene may increase the risk of prostate cancer, intracerebral hemorrhage, and cardiovascular and total mortality irrespective of smoking status.[8][9]

Industrial sources

[edit]

β-carotene is industrially made either by total synthesis (see Retinol § Industrial synthesis) or by extraction from biological sources such as vegetables, microalgae (especially Dunaliella salina), and genetically-engineered microbes. The synthetic path is low-cost and high-yield.[35]

Research

[edit]

Medical authorities generally recommend obtaining beta-carotene from food rather than dietary supplements.[8] A 2013 meta-analysis of randomized controlled trials concluded that high-dosage (≥9.6 mg/day) beta-carotene supplementation is associated with a 6% increase in the risk of all-cause mortality, while low-dosage (<9.6 mg/day) supplementation does not have a significant effect on mortality.[36] Research is insufficient to determine whether a minimum level of beta-carotene consumption is necessary for human health and to identify what problems might arise from insufficient beta-carotene intake.[37] However, a 2018 meta-analysis mostly of prospective cohort studies found that both dietary and circulating beta-carotene are associated with a lower risk of all-cause mortality. The highest circulating beta-carotene category, compared to the lowest, correlated with a 37% reduction in the risk of all-cause mortality, while the highest dietary beta-carotene intake category, compared to the lowest, was linked to an 18% decrease in the risk of all-cause mortality.[38]

Macular degeneration

[edit]
Main article: Macular degeneration

Age-related macular degeneration (AMD) represents the leading cause of irreversible blindness in elderly people. AMD is an oxidative stress, retinal disease that affects the macula, causing progressive loss of central vision.[39] β-carotene content is confirmed in human retinal pigment epithelium.[16] Reviews reported mixed results for observational studies, with some reporting that diets higher in β-carotene correlated with a decreased risk of AMD whereas other studies reporting no benefits.[40] Reviews reported that for intervention trials using only β-carotene, there was no change to risk of developing AMD.[8][40][41]

Cancer

[edit]

A meta-analysis concluded that supplementation with β-carotene does not appear to decrease the risk of cancer overall, nor specific cancers including: pancreatic, colorectal, prostate, breast, melanoma, or skin cancer generally.[8][42] High levels of β-carotene may increase the risk of lung cancer in current and former smokers.[8][43] Results are not clear for thyroid cancer.[44]

Cataract

[edit]

A Cochrane review looked at supplementation of β-carotene, vitamin C, and vitamin E, independently and combined, on people to examine differences in risk of cataract, cataract extraction, progression of cataract, and slowing the loss of visual acuity. These studies found no evidence of any protective effects afforded by β-carotene supplementation on preventing and slowing age-related cataract.[45] A second meta-analysis compiled data from studies that measured diet-derived serum beta-carotene and reported a not statistically significant 10% decrease in cataract risk.[46]

Erythropoietic protoporphyria

[edit]

High doses of β-carotene (up to 180 mg per day) may be used as a treatment for erythropoietic protoporphyria, a rare inherited disorder of sunlight sensitivity, without toxic effects.[8][9]

Food drying

[edit]

Foods rich in carotenoid dyes show discoloration upon drying. This is due to thermal degradation of carotenoids, possibly via isomerization and oxidation reactions.[47]

See also

[edit]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Β-Carotene

View on Grokipedia
from Grokipedia
β-Carotene is a naturally occurring, red-orange classified as a provitamin A carotenoid, with the molecular formula C₄₀H₅₆, consisting of two β-ionone rings linked by a polyene chain containing 9 conjugated double bonds, resulting in a total of 11 conjugated double bonds. It is insoluble in but soluble in non-polar organic solvents such as and , with a of approximately 178 °C, and serves as a key biosynthetic precursor to in animals. Abundant in , β-carotene is the primary responsible for the vibrant colors in foods like carrots, sweet potatoes, pumpkins, and leafy greens, where it accumulates in chloroplasts and chromoplasts. In the human diet, it functions as the most efficient provitamin A , undergoing central cleavage by the β-carotene 15,15'-oxygenase (BCO1) in the intestinal mucosa to yield two molecules of , which can then be converted to () or . This bioconversion is crucial for maintaining status, particularly in populations relying on plant-based diets, as preformed is primarily sourced from animal products. Beyond its role in vitamin A synthesis, β-carotene exhibits potent properties by scavenging free radicals and quenching , thereby protecting cells from and contributing to photoprotection against UV-induced damage. These activities have been linked to potential benefits in reducing the risk of chronic diseases, including certain cancers and age-related macular degeneration, though high-dose supplementation trials have shown mixed results, with some indicating no protective effect or even increased risk in smokers. Commercially, β-carotene is synthesized or extracted for use as a food colorant (E160a), nutritional supplement, and in for its skin-protective effects.

Chemical Properties

Molecular Structure

β-Carotene has the C₄₀H₅₆ and a molecular weight of 536.87 g/mol. It is classified as a tetraterpenoid, consisting of eight units arranged in a linear polyene chain with 11 conjugated double bonds, terminated by two β-ionone rings. The predominant natural form is the all-trans , but exposure to or can induce cis-trans , producing cis forms such as 9-cis-β-carotene and 13-cis-β-carotene. Unlike , which possesses one β-ionone ring and one ε-ionone ring, or , which is acyclic without end rings, β-carotene's symmetric structure with two β-ionone rings distinguishes it among .

Physical Characteristics

β-Carotene appears as a dark red to orange crystalline solid, serving as a strongly colored responsible for the hues in various plants and fruits. It has a melting point of 183 °C when heated in an evacuated tube, beyond which it tends to decompose rather than boil at , with an estimated boiling point around 645–655 °C. The compound is insoluble in but exhibits good solubility in nonpolar organic solvents, including , , , and . β-Carotene is highly sensitive to light exposure, which accelerates its oxidative degradation and results in color fading; it also shows instability under and in the presence of oxygen, though it maintains greater stability when incorporated into oils. Its characteristic pigmentation arises from spectral properties featuring UV-Vis absorption maxima at 449–478 nm in , with a prominent peak near 450 nm.

Biological Role

Provitamin A Activity

β-Carotene is one of the three primary provitamin A , alongside and , that can be converted into in the . It was first isolated in 1831 by Heinrich Wilhelm Wackenroder from carrots. Its role as a provitamin A was established in 1930 by , who demonstrated that β-carotene could be converted to vitamin A through experiments on rats. In the , β-carotene undergoes central cleavage by the β-carotene 15,15'-monooxygenase 1 (BCMO1), yielding two molecules of . is then reduced to , the main form of , and can be further oxidized to , which plays a critical role in gene regulation for , differentiation, and immune function. As a key source of , particularly in plant-based diets, inadequate β-carotene intake contributes to in vulnerable populations, such as those in developing regions relying on staple foods low in provitamin A , leading to disorders like night blindness due to impaired regeneration in the . Conversion efficiency to varies by individual factors like , but β-carotene remains an essential dietary contributor.

Antioxidant Properties

β-Carotene functions as a potent by scavenging (ROS), with a particular efficacy in quenching . This physical quenching process occurs at a near diffusion-controlled rate, characterized by a rate constant of 1.2×1010 M−1s−11.2 \times 10^{10} \, \mathrm{M^{-1} s^{-1}}, which allows it to effectively neutralize this highly reactive form of oxygen before it can damage cellular components. In biological systems, this mechanism helps mitigate by preventing the propagation of ROS-induced chain reactions. Due to its lipophilic nature, β-carotene preferentially localizes within cell membranes and lipoproteins, where it integrates into the lipid bilayer to intercept ROS at sites prone to peroxidation. This positioning enables it to inhibit lipid peroxidation by trapping peroxyl radicals and stabilizing membrane integrity against oxidative disruption. Furthermore, β-carotene exhibits synergistic interactions with other antioxidants, such as vitamin E, where it can regenerate the oxidized form of vitamin E (tocopheroxyl radical), thereby enhancing the overall antioxidant network and prolonging the protective effects in lipid environments. Beyond general ROS scavenging, β-carotene provides non-vitamin A-related against photooxidative in tissues like the skin and eyes, where exposure to light generates and other oxidants. studies have demonstrated that β-carotene supplementation reduces UV-induced DNA , such as strand breaks and oxidative lesions, by quenching photo-generated ROS and limiting their interaction with genomic material. This protective role underscores its importance in preventing cellular alterations from environmental oxidative stressors.

Metabolism

Absorption and Bioavailability

β-Carotene is primarily absorbed in the , where it is incorporated into mixed micelles formed by salts and dietary , facilitating its solubilization and uptake by enterocytes via passive across the apical . This is essential, as β-carotene's hydrophobic nature prevents direct absorption from the aqueous intestinal lumen without emulsification. Bioavailability of β-carotene is significantly enhanced by the presence of , with at least 3-5 g per meal required to optimize formation and absorption efficiency. Conversely, high content can inhibit absorption by binding β-carotene or interfering with stability, while reduces uptake, possibly due to impaired activity in formation. Cooking or mechanical processing of plant foods improves by disrupting cell walls and matrices, releasing bound β-carotene for better incorporation into ; for instance, pureed cooked carrots yield higher plasma levels than raw forms. Genetic variations in the β-carotene 15,15'-monooxygenase 1 (BCMO1) gene, which encodes the enzyme for subsequent conversion, also influence overall uptake and circulating levels, with certain alleles associated with lower absorption efficiency. Absorption occurs predominantly through passive diffusion, though scavenger receptor class B type I (SR-BI) and cluster determinant 36 () on enterocytes facilitate uptake from micelles, contributing to the process without strict dominance. In humans, typical absorption efficiency ranges from 10-30% for dietary sources, with higher rates (up to 65%) observed for purified supplements due to reduced matrix interference.

Conversion to Vitamin A

β-Carotene is converted to primarily through central cleavage in the enterocytes of the , catalyzed by the β,β-carotene 15,15'-monooxygenase 1 (BCMO1). This enzymatic reaction symmetrically cleaves the β-carotene molecule at its central (15,15' position), yielding two molecules of (vitamin A aldehyde). The biochemical equation for this oxidative cleavage is: β-C40H56+O2→2 C20H28O\beta\text{-C}_{40}\text{H}_{56} + \text{O}_{2} \to 2 \text{ C}_{20}\text{H}_{28}\text{O} The produced is then reduced to (vitamin A alcohol) by retinal reductases, such as members of the short-chain dehydrogenase/reductase family, including retinol dehydrogenase enzymes that utilize NADPH as a cofactor. This is incorporated into chylomicrons and transported via the to the liver, where it is esterified primarily by :retinol acyltransferase (LRAT) to form retinyl esters, mainly , for storage in hepatic stellate cells. The conversion process is tightly regulated by homeostatic mechanisms responsive to status; upregulates BCMO1 expression to enhance cleavage, while high levels of or its metabolites, such as , suppress BCMO1 transcription and activity to prevent excess accumulation. Genetic variations in the BCMO1 , particularly single nucleotide polymorphisms (SNPs) such as rs12934922 (A379V) and rs7501331 (R267S), significantly influence conversion efficiency, with variant s reducing enzymatic activity by 30-70% in vitro and leading to lower serum responses to β-carotene intake. These SNPs have frequencies of approximately 24% for A379V and 42% for R267S in diverse populations, resulting in 20-50% of individuals exhibiting reduced conversion efficiency and classified as "poor converters." Although alternative eccentric cleavage pathways exist, producing β-apocarotenals such as β-apo-10'-carotenal and β-apo-14'-carotenal, these are minor contributors to production in humans and primarily yield non-provitamin A metabolites.

Excretion

The primary route of β-carotene excretion is fecal elimination of the unabsorbed portion, which typically accounts for 60-90% of dietary intake due to limited intestinal absorption. Studies using radiolabeled β-carotene in humans have shown that 53-57% of an oral dose is recovered in feces within the first 48 hours, reflecting the unabsorbed fraction, with the remainder distributed between absorption and slower elimination. Dietary factors, such as intake, can further enhance fecal excretion by reducing . Metabolites of β-carotene, particularly oxidized forms like β-apo-carotenals and β-apo-carotenoic acids, are primarily excreted via following phase II conjugation, such as , to increase water solubility. These apocarotenoids arise from eccentric cleavage and subsequent oxidation, with urinary recovery representing a minor but detectable portion of the total dose, often less than 2% in long-term kinetic studies. Intact β-carotene exhibits negligible urinary loss owing to its lipophilic nature and lack of significant renal . Biliary excretion plays a role in the elimination of β-carotene derivatives, particularly retinyl esters formed during conversion to , which are secreted into and undergo for reabsorption in the intestine. This recycling mechanism conserves status but also contributes to gradual fecal loss of metabolites over time, with accounting for up to 8% of labeled activity in short-term studies. Excess β-carotene accumulates in lipophilic tissues such as adipose and , where it is stored without rapid turnover, contributing to prolonged retention compared to plasma levels. This storage occurs via incorporation into chylomicrons and subsequent deposition, with pigmentation observable after chronic high intake. The plasma half-life of β-carotene is approximately 6-11 days following , reflecting a balance between uptake, distribution, and elimination, while tissue half-lives in adipose and other depots extend to weeks or longer due to slow release. In kinetic analyses using , the apparent distribution reached 13 days, underscoring the compound's persistence in circulation before full clearance.

Nutritional Aspects

Conversion Factors

The conversion of β-carotene to activity is quantified using Retinol Activity Equivalents (RAEs), a system established to account for differences in between preformed and provitamin A carotenoids like β-carotene. According to the Institute of Medicine (IOM) 2001 report, 1 μg RAE equals 1 μg , 12 μg dietary β-carotene from food sources, or 2 μg supplemental β-carotene typically provided in oil-based formulations. These factors reflect updated estimates of absorption and efficiency, with dietary β-carotene absorption ranging from 10% to 30% in mixed diets, leading to a ratio of approximately 12:1 for plant-derived sources. Prior conversion systems, such as Equivalents (REs), used a 6:1 ratio for dietary β-carotene and overestimated activity by a factor of 2 to 3 times due to assumptions of higher absorption rates. For practical calculations in mixed diets, the 12:1 factor is applied to β-carotene content from and other plant foods to estimate total activity. An older unit, the (IU), provides another equivalence measure: 1 IU of vitamin A equals 0.3 μg retinol or approximately 0.6 μg β-carotene in oil dispersions, though this varies for dietary forms where 1 IU dietary β-carotene equates to about 0.05 μg RAE.
UnitEquivalence to 1 μg Retinol (or 1 RAE)
Dietary β-carotene12 μg
Supplemental β-carotene (in oil)2 μg
IU vitamin A (retinol)~3.33 IU
These conversion factors have limitations, as efficiency can vary significantly based on individual genetic factors, such as polymorphisms in genes like BCMO1 that influence activity in cleavage. Additionally, the food matrix— including the presence of fats, , and processing methods—affects absorption, with equivalency ratios ranging from 9:1 to 16:1 in typical Western diets rather than a fixed 12:1.

Dietary Recommendations

There is no separate recommended dietary allowance (RDA) for β-carotene, as its nutritional role is addressed through the RDA for , expressed in retinol activity equivalents (RAE). For adults, the RDA is 900 μg RAE per day for men and 700 μg RAE per day for women, which can be met partly or fully through provitamin A carotenoids like β-carotene from dietary sources. The absence of a specific dietary requirement for β-carotene stems from the body's ability to regulate its conversion to () on an as-needed basis, thereby preventing even with higher intakes. No tolerable upper intake level has been established for β-carotene obtained from food sources, due to its low profile. For supplemental β-carotene, a daily intake not exceeding 3.5 mg is generally advised to minimize potential risks, particularly in smokers, based on evidence from large-scale intervention trials showing adverse effects at higher doses (15–30 mg/day). In regions with , the recommends multiple micronutrient supplementation for pregnant women, including 3.5 mg of β-carotene daily as part of formulations like UNIMMAP to support maternal and fetal health without the risks associated with preformed . Population-specific needs for β-carotene intake are higher in developing countries, where affects approximately 190 million preschool children and causes significant morbidity, necessitating targeted dietary or supplemental strategies to achieve sufficiency.

Health Effects

Potential Benefits

As a provitamin A carotenoid, β-carotene contributes to preventing , a form of corneal damage leading to blindness associated with , by serving as a precursor to essential for maintaining epithelial integrity in the eye. It also supports immune function through its role in vitamin A metabolism, which is critical for immune competency and . In populations with , supplementation with β-carotene or has been shown to reduce ; a seminal of community-based trials from the reported a 23% reduction in all-cause mortality among children aged 6 months to 5 years. β-Carotene exhibits properties that may mitigate implicated in , with observational studies linking higher dietary intake to reduced risk. For instance, prospective cohort analyses indicate that elevated circulating β-carotene levels are associated with approximately a 32% lower risk of mortality. Additionally, oral supplementation with β-carotene provides photoprotective effects for skin health; daily intake of 30 mg has been found to confer a sun protection factor equivalent to about 4, reducing from exposure as demonstrated in meta-analyses of supplementation trials. In states of deficiency, β-carotene enhances immune modulation by promoting T-cell function, including increases in CD4+ lymphocytes and interleukin-2 receptor-positive T cells, which bolster adaptive immunity. Recent meta-analyses of prospective cohort studies, including those from 2023, further link higher β-carotene intake or serum levels to reduced all-cause mortality, particularly in older adults, underscoring its role in overall through and provitamin A mechanisms.

Side Effects

β-Carotene obtained from dietary sources is generally considered safe and does not produce adverse effects, even at higher intakes from carotenoid-rich foods. In contrast, high-dose supplementation can lead to mild gastrointestinal disturbances, such as or loose stools. Unlike preformed , which can accumulate and cause , β-carotene exhibits no such because its enzymatic conversion to in the body is tightly regulated based on vitamin A status. Excessive intake may result in hypercarotenemia, a benign and reversible condition involving elevated serum β-carotene levels without systemic symptoms. Allergic reactions to β-carotene are uncommon and typically occur in response to supplements rather than food sources. Monitoring plasma β-carotene concentrations is advisable, as levels exceeding 1.5 μmol/L suggest excessive intake.

Carotenodermia

Carotenodermia, also known as carotenemia or , is a benign condition characterized by a yellow-orange discoloration of the skin resulting from elevated levels of β-carotene and other in the blood. This pigmentation typically manifests in areas with thicker , such as the palms of the hands, soles of the feet, and nasolabial folds, where the color may appear most pronounced due to the preferential deposition of lipophilic in these keratin-rich layers. The condition is harmless and does not affect mucous membranes or the , distinguishing it from other forms of . The primary cause of carotenodermia is excessive intake of β-carotene-rich foods or supplements, leading to accumulation in the skin's outer layer without conversion to . It commonly occurs after prolonged consumption exceeding 30 mg of β-carotene per day for several weeks, often observed in vegetarians, vegans, or individuals using high-dose supplements for purported health benefits. In such cases, plasma carotenoid levels surpass 4.0 µg/mL, triggering visible changes after 25–42 days of supplementation. Diagnosis is primarily clinical, based on the characteristic skin coloration and a detailed dietary history revealing high carotenoid intake. To differentiate from jaundice, examination confirms the absence of yellowing in the sclera and mucous membranes, as bilirubin does not cause carotenodermia; serum β-carotene levels may be measured if needed, but biopsy is rarely required. Upon cessation of excess β-carotene intake, the pigmentation gradually resolves as the body metabolizes and excretes the accumulated , typically within 2–6 weeks, though full normalization can take up to several months in severe cases. First described in 1904 by Carl von Noorden as "xanthosis diabetica," the condition was initially linked to but later recognized as a harmless, diet-related phenomenon that primarily raises cosmetic concerns for affected individuals.

Drug Interactions

β-Carotene absorption in the gastrointestinal tract can be significantly reduced by certain medications that interfere with bile acids or dietary fats. Cholestyramine, a bile acid-binding resin used to treat hypercholesterolemia, decreases the intestinal absorption of lipids, including β-carotene, resulting in lower serum concentrations of the carotenoid. Similarly, orlistat, a lipase inhibitor prescribed for weight management, impairs fat digestion and absorption, reducing β-carotene bioavailability by approximately one-third when coadministered. Patients taking these medications are advised to separate β-carotene supplementation by at least two hours to minimize interference. Chronic alcohol consumption may impair the hepatic conversion of β-carotene to () through alcohol-induced liver damage, which disrupts metabolic function. This interaction is particularly relevant in individuals with ongoing heavy alcohol use, where liver dysfunction can lead to decreased efficiency in processing. β-Carotene exhibits no major interactions with enzymes, and its supplements are generally considered safe for concurrent use with most prescription medications, with only a limited number of moderate interactions reported.

Lung Cancer Risk in Smokers

Two large randomized controlled trials conducted in the 1990s demonstrated that high-dose β-carotene supplementation increases the risk of lung cancer in smokers. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, involving 29,133 male smokers in Finland who received 20 mg/day of β-carotene for 5 to 8 years, reported an 18% increase in lung cancer incidence (relative risk [RR] 1.18; 95% confidence interval [CI] 1.03-1.36) compared to placebo. Similarly, the Beta-Carotene and Retinol Efficacy Trial (CARET), which enrolled 18,314 participants at high risk for lung cancer (including current and former smokers and asbestos-exposed individuals) receiving 30 mg/day of β-carotene plus 25,000 IU/day of retinol for an average of 4 years, found a 28% higher incidence of lung cancer (RR 1.28; 95% CI 1.04-1.57) in the active treatment group versus placebo. These trials were terminated early due to the observed harm. The proposed mechanism for this adverse effect involves β-carotene acting as a pro-oxidant at supraphysiological doses in the oxidative environment of smokers' lungs, potentially exacerbating DNA damage from cigarette smoke rather than providing protection. In contrast, dietary sources of β-carotene from fruits and vegetables, which provide lower doses in a complex matrix with other nutrients, have not been associated with increased risk in smokers and may even confer protective effects based on observational studies. Only synthetic supplements at high doses (20-30 mg/day) have been implicated in this risk. Major health organizations recommend against β-carotene supplementation for current or former smokers due to these findings. The U.S. Preventive Services Task Force (USPSTF) advises against the use of β-carotene supplements for in this population (Grade D recommendation). Follow-up analyses from the ATBC and trials confirmed no increased lung cancer risk among non-smokers or never-smokers in these cohorts. A 2022 systematic review and of randomized trials further substantiated the smoker-specific harm, reporting a 16% increased risk of with β-carotene supplementation overall (RR 1.16; 95% CI 1.06-1.26), with subgroup analyses highlighting elevated risks primarily in smokers.

Research

Eye Health

β-Carotene has been investigated for its potential role in preventing age-related (AMD), a leading cause of vision loss in older adults. The Age-Related Eye Disease Study (AREDS), a multicenter randomized conducted from 1992 to 1998, evaluated high-dose supplementation with 15 mg β-carotene, 500 mg , 400 IU , and 80 mg in individuals with intermediate AMD or advanced AMD in one eye. The results, published in 2001, demonstrated a 25% reduction in the risk of progression to advanced AMD over five years in this high-risk population. Observational studies have associated higher dietary intake of β-carotene with a reduced of , though (RCT) evidence remains limited. Meta-analyses of cohort and case-control studies indicate that individuals with the highest β-carotene intake experience approximately 20-30% lower odds of developing age-related compared to those with the lowest intake, potentially due to its properties. However, RCTs, such as the Women's Antioxidant Cardiovascular Study, have not shown a significant preventive effect from β-carotene supplementation alone on incidence or progression. In the , β-carotene contributes to eye health by acting as an that quenches (ROS) generated by light exposure and metabolic processes. It also absorbs harmful blue light wavelengths (400-500 nm), reducing photochemical damage to retinal cells and the macular pigment. As a provitamin A compound, β-carotene supports overall visual function by converting to , essential for in low-light vision. Recent research has shifted preferences toward and over β-carotene in supplements due to the latter's association with increased risk in smokers. The AREDS2 trial (2006-2012) replaced β-carotene with 10 mg lutein and 2 mg zeaxanthin in the formula, finding equivalent protection against AMD progression without the lung risks, as confirmed in long-term follow-up studies through 2023. In -deficient regions, supplementation in children has been shown to reduce measles-related blindness by preventing corneal damage and supporting immune responses, with WHO guidelines recommending it to avert up to 500,000 annual cases of . As a provitamin A, β-carotene from diet contributes to status but is not the primary supplemental form.

Cancer Prevention

Epidemiological evidence from cohort studies indicates that higher dietary intake of β-carotene from food sources is associated with a reduced of certain cancers, including and . For , meta-analyses of multiple cohort studies have shown a significant reduction, with pooled estimates suggesting up to a 20-30% lower incidence among individuals with the highest intakes compared to the lowest. Similarly, for , prospective cohort analyses report a 20-40% reduction linked to elevated dietary β-carotene levels, particularly in premenopausal women, attributed to the compound's presence in carotenoid-rich and fruits. In contrast, randomized controlled trials of β-carotene supplements have generally demonstrated no protective effect against cancer incidence in non-smokers, with some showing neutral or even adverse outcomes in high-risk groups. The potential anticancer mechanisms of β-carotene involve its properties, which neutralize and reduce oxidative damage to in cells, as well as anti-proliferative effects observed on tumor cells. In laboratory studies, β-carotene inhibits cell cycle progression and induces in various lines, including those from and tumors, by modulating pathways such as p21 expression and activation. These effects are dose-dependent and more pronounced at physiological concentrations mimicking dietary exposure rather than supraphysiological supplement levels. Major clinical trials, such as the Physicians' Health Study (1996), involving over 22,000 healthy male non-smokers, found no significant reduction in overall cancer incidence after 12 years of β-carotene supplementation at 50 mg every other day. This lack of benefit echoes findings from other large trials, prompting caution following the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) and studies, which reported increased risk in smokers taking supplements (as detailed in the Lung Cancer Risk in Smokers section). Recent research from 2024 highlights how dietary β-carotene may enhance protection through gut modulation, where it promotes beneficial bacterial composition and short-chain production, potentially reducing prevalence by 20-30% in high-intake groups. Overall, the International Agency for Research on Cancer (IARC) does not classify β-carotene as carcinogenic from dietary sources, which appear protective against various cancers, but advises against high-dose supplements, particularly for smokers, due to evidence of increased risk in intervention trials. This distinction underscores the importance of obtaining β-carotene through whole foods rather than isolated supplementation for potential cancer preventive benefits.

Cardiovascular Effects

Observational studies have consistently linked higher plasma levels of β-carotene to reduced (CVD) risk. For instance, prospective cohort analyses, including data from large populations like the , indicate that elevated plasma β-carotene concentrations correlate with 20-30% lower CVD mortality rates, likely reflecting overall dietary patterns rich in fruits and vegetables. Similarly, a of multiple cohorts reported relative risks ranging from 0.70 to 0.83 for major coronary events in individuals with high serum β-carotene, underscoring an inverse association independent of other antioxidants. Randomized controlled trials of β-carotene supplementation, however, have largely failed to demonstrate cardiovascular benefits and suggest potential risks in certain populations. The Physicians' Health Study (1996), involving over 22,000 healthy men supplemented with 50 mg β-carotene every other day for 12 years, found no reduction in the incidence of cardiovascular events or mortality. Likewise, the Heart Protection Study (2002), a of 20,536 high-risk individuals receiving 20 mg β-carotene daily alongside vitamins C and E, reported no decrease in major vascular events, with hazard ratios near 1.00 for both primary and secondary prevention.09328-5/fulltext) In high-risk groups, such as smokers, supplementation has been associated with increased overall mortality, including trends toward higher CVD deaths in trials like and ATBC, prompting early termination of some studies. The proposed cardiovascular protective mechanisms of β-carotene center on its properties, particularly the inhibition of (LDL) oxidation, which contributes to atherosclerotic plaque formation. and studies demonstrate that β-carotene incorporates into LDL particles, prolonging their resistance to oxidative modification by free radicals. Additionally, β-carotene exerts anti-inflammatory effects on vascular by modulating bioavailability and suppressing pro-inflammatory pathways like , potentially improving endothelial function and reducing atherogenesis. These actions align with its role in observational benefits but have not translated to clinical outcomes from isolated supplementation. Recent post-2020 meta-analyses reinforce the distinction between dietary and supplemental β-carotene, emphasizing benefits from whole-food sources over isolated forms. A 2022 of 31 randomized trials concluded that β-carotene supplements provide no mortality benefit (RR 1.02, 95% CI 0.98-1.05) and may elevate CVD risk in vulnerable subgroups. In contrast, analyses of serum levels and dietary patterns, such as the , highlight synergistic effects of combined (e.g., β-carotene with and ), associating higher intake with 15-25% lower CVD incidence through holistic and synergies rather than β-carotene alone. These findings advocate prioritizing carotenoid-rich diets for cardiovascular .

Skin Protection

β-Carotene has been investigated for its role in protecting the skin from (UV) radiation damage, primarily through its properties that quench free radicals generated by UV exposure. Randomized controlled trials (RCTs) from the early 2000s demonstrated that oral supplementation with 24 mg/day of β-carotene for 10-12 weeks significantly increases the minimal dose (MED), the threshold for UV-induced skin reddening, by approximately 20-30% in healthy volunteers. This effect positions β-carotene as an "internal ," enhancing cutaneous resistance to sunburn without replacing topical photoprotectants. A of multiple studies confirmed this photoprotective benefit, with doses ranging from 12-30 mg/day leading to consistent elevations in erythema thresholds across diverse populations. In the context of erythropoietic protoporphyria (EPP), a rare disorder causing severe photosensitivity due to protoporphyrin accumulation, high-dose β-carotene has been historically used for symptom management, with doses of 90-120 mg/day reported in older studies to increase tolerance in some patients. However, recent evidence indicates unclear or no benefit, and newer therapies like are preferred. Long-term administration, up to 180 mg/day in adults, sustains this protection in responsive cases, though monitoring for hypercarotenemia—a reversible yellowing of the skin known as carotenodermia—is recommended. For oral , a precancerous mucosal , β-carotene at 30 mg/day for 3-6 months induces regression in approximately 30% of cases, as evidenced by clinical trials showing partial or complete resolution without significant . However, it is not considered a first-line due to variable long-term efficacy and the availability of more potent retinoids; its use is typically reserved for mild cases or as an adjunct. Recent research as of 2024 has explored combination approaches, including topical and oral β-carotene formulations for management, where integrated therapies reduce plaque severity by modulating and . Additionally, studies on the gut- axis indicate that β-carotene supplementation alters microbial composition, promoting beneficial that enhance barrier function and reduce UV-related , opening avenues for microbiome-targeted dermatological interventions. These advances highlight β-carotene's potential in non-cancer applications, though larger trials are needed to address gaps in post-pandemic UV exposure contexts.

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