IngredientsCanthaxanthin is a keto-carotenoid pigment widely distributed in nature. Its systematic chemical name is β,β-carotene-4,4′-dione, also written as 4,4′-diketo-β-carotene. This compound is produced as the major carotenoid pigment in several orange- and dark-pink-pigmented organisms. The chemical formula of canthaxanthin is C₄₀H₅₂O₂. Its CAS number is 514-78-3 and its molecular weight is 564.84 g/mol. Carotenoids belong to a larger class of phytochemicals known as terpenoids. Within the carotenoid family, canthaxanthin is classified as a xanthophyll and more specifically as a ketocarotenoid, distinguished by the presence of keto (carbonyl) groups at the 4 and 4′ positions of its β-ionone rings. It carries no provitamin A activity because its beta-ionone rings are fully oxidized.
All carotenoids share common chemical features, such as a polyisoprenoid structure, a long polyene chain forming the chromophore, and near symmetry around the central double bond. Canthaxanthin is formed as an intermediate compound in β-carotene metabolism to astaxanthin. Its characteristic deep red-orange color arises from the extensive conjugated double-bond system along the C₄₀ backbone, which allows strong absorption of visible light in the blue-green region (~470–490 nm).
Common synonyms include beta-carotene-4,4′-dione, Carophyll Red, Food Orange 8, Roxanthin Red 10, and the informal terms "tanning pill" and "tanning tablet." Canthaxanthin is associated with E number E161g and is approved for use as a food coloring agent in different countries, including the United States and the EU; however, it is not approved for use in Australia and New Zealand. In the United States, canthaxanthin is approved for specific uses in animal food, as listed in 21 CFR 73.75.
Canthaxanthin is an orange-red keto-carotenoid that occurs naturally and is also manufactured by synthetic methods for regular applications. In nature, canthaxanthin mainly exists in microbes such as different bacterial species, fungi, and algae, as well as in animals such as crustaceans, certain fishes, and birds.
Fungi (primary discovery source): This pigment was first isolated from an edible chanterelle mushroom, Cantharellus cinnabarinus, as a major component in a mixture of carotenoid extracts. The edible mushroom Cantharellus cinnabarinus contains a complicated mixture of carotenoid pigments; the major component was isolated in crystalline form and named canthaxanthin. Isolation of canthaxanthin was first reported in the mid-20th century from this species. Other fungi such as Aspergillus carbonarius and the yeast Xanthophyllomyces dendrorhous also produce it, contributing to their characteristic coloration.
Bacteria: Canthaxanthin is produced as the major carotenoid pigment by orange- and dark-pink-pigmented bacteriochlorophyll-containing Bradyrhizobium strains isolated from stem nodules of Aeschynomene species. It has additionally been identified from Brevibacterium, Micrococcus roseus, and various other non-photosynthetic bacteria.
Algae: Canthaxanthin is produced as a secondary carotenoid in several green algae, blue-green algae, and bacteria. It is synthesized either at the end of the growth phase instead of or in addition to primary carotenoids.
Animals: Among animals, canthaxanthin bioaccumulates in tissues via consumption of carotenoid-rich prey, enhancing pigmentation without endogenous synthesis. In aquatic species, it is prominent in crustaceans like shrimp and krill, whose shells and eggs impart the pigment to predators. Humans and other animals cannot synthesize carotenoids de novo and must obtain them from their diet. Fish such as salmon (Salmo trutta), rainbow trout (Oncorhynchus mykiss), carp (Cyprinus carpio), golden mullet (Mugil auratus), and seabream exhibit flesh and skin coloration from dietary uptake. Coloration caused by canthaxanthin can be observed in flamingo feathers, koi carp skin, salmon and trout flesh, and egg yolks.
The benefits of dietary carotenoids in health are encouraging the shift of commercial production of canthaxanthin from chemical synthesis to consumption or extraction from natural sources. A commonly used petrochemical-based material called "ketoisophorone" serves as a precursor for synthesizing xanthophylls. Biosynthetically, the orange-red keto-carotenoid is synthesized from β-carotene via a β-carotene ketolase enzyme.
Canthaxanthin is commercially available in several forms:
In 2017, the canthaxanthin market size reached $75 million, with 40% of volume share accounted for by animal feed applications. Canthaxanthin has been licensed in over 70 countries in Europe, America, and Asia.
Canthaxanthin does not belong to an ancient herbal or ethnobotanical tradition in the way that many plant-based supplements do. Its history is predominantly 20th-century industrial and biomedical, beginning with its chemical identification and subsequent commercial development.
Scientific Discovery (1950): The pigment was formally named and characterized following its isolation from Cantharellus cinnabarinus by Haxo in 1950. The compound's name was derived directly from the genus of that mushroom.
Food Coloring Use (1950s–1970s): Following chemical characterization, canthaxanthin began to be used as a food colorant in processed foods. Its vivid red-orange hue made it valuable for coloring products such as tomato-based sauces, fish pastes, and certain beverages. Its use as a food additive preceded detailed regulatory assessment.
Aquaculture Pigmentation (1970s–present): Despite not being widespread in the aquatic environment and not being the natural carotenoid found in salmonid, canthaxanthin has played an important role as a pigment source in the aquaculture industry. As salmon farming expanded in the 1970s and 1980s, canthaxanthin (and astaxanthin) became standard feed additives to produce the pink-orange flesh coloration that consumers expected. In the poultry industry, it is used as a feed additive to obtain red color in egg yolks and skins.
Oral "Tanning" Use (Late 1970s–1990s): Canthaxanthin has been a popular over-the-counter oral artificial tanning agent in Europe, Canada, and Australia since 1979. It was used as an agent for skin bronzing, with the principle that carotenoid deposition in subcutaneous fat and the dermis would produce an orange-tan appearance. The skin color accumulates over a 2-week period, then fades in about 2 weeks when the product is discontinued. This use was entirely a commercial-era phenomenon rather than a traditional or folk practice; it arose from the pharmaceutical industry's awareness of carotenodermia observed in individuals who consumed high-carotenoid diets.
Dermatological Applications (1970s–1990s): Canthaxanthin has been used as a food-coloring agent, for skin pigmentation in the treatment of vitiligo, and for the treatment of photosensitivity disorders such as erythropoietic protoporphyria, psoriasis, and photosensitive eczema. These applications emerged from clinical observations that orally administered carotenoids could alter skin photosensitivity. Experimental use was successful for photoprotection for erythropoietic protoporphyria and cosmetic improvement in vitiligo.
Regulatory Restrictions on Oral Tanning: In Germany, the office of the federal board of health refused the permit for oral tanning agents containing canthaxanthin in 1985. Other jurisdictions followed with restrictions after reports of retinal crystal deposition emerged. The oral tanning tablet market effectively ceased in most countries with regulated pharmaceutical markets by the 1990s, though the compound continued to be used clinically for photosensitivity disorders under medical supervision.
Canthaxanthin is itself the primary active compound of interest; it is not a mixture of multiple active ingredients in the way an herbal extract might be. Its biological activity derives directly from its molecular structure.
Canthaxanthin acts as a strong antioxidant, owing to the location of keto groups at the 4 and 4′ positions in the β-ionone ring. The extended conjugated double-bond system of the C₄₀ polyene backbone — comprising 11 conjugated double bonds — is the fundamental structural feature enabling both its intense coloration and its ability to interact with reactive oxygen species and triplet-state molecules.
Unlike α-carotene or β-carotene, canthaxanthin possesses no provitamin A activity. The keto substitutions at both 4 and 4′ positions of the terminal rings prevent enzymatic cleavage to retinal. This has been confirmed by the observation that the active carotenoid canthaxanthin did not induce the vitamin A-inducible gene retinoic acid receptor-beta. Thus, none of canthaxanthin's biological effects are mediated through the vitamin A pathway.
Canthaxanthin, being a ketocarotenoid, exhibits higher antioxidant and free radical scavenging properties than other carotenes and xanthophylls. Studies have shown that canthaxanthin is capable of scavenging reactive oxygen species and quenching singlet oxygen. The rate constant for singlet oxygen quenching for canthaxanthin is near 1.45 × 10¹⁰ mol/s. Canthaxanthin acts as a strong antioxidant by reacting with phenoxyl radicals generated by the one-electron metabolism of phenolic compounds, the reaction being catalyzed by the peroxidase enzyme. The antioxidant potential of canthaxanthin against photo-oxidation by energy dissipation is well established.
In terms of relative antioxidant ranking among carotenoids, comparative studies have shown that the order of radical scavenging ability among carotenoids is lycopene > β-cryptoxanthin ≈ β-carotene > lutein ≈ zeaxanthin > α-carotene > echinenone > canthaxanthin = astaxanthin. Thus, while canthaxanthin is a capable antioxidant, it is not the most potent carotenoid in this respect.
In vivo experiments revealed that canthaxanthin supplementation led to a decrease in lipid peroxidation to prevent induced liver DNA damage in rats and to enhance the antioxidant defense in rat liver. These findings are from animal studies and cannot be directly extrapolated to humans.
A distinct and provitamin A-independent mechanism of canthaxanthin has been identified at the cellular level. In mouse C3H10T1/2 cells, cancer chemopreventive activity is highly correlated with the ability of carotenoids to up-regulate gap junctional intercellular communication. Carotenoids increase the expression of connexin43, a gene that encodes a major gap junction protein. This effect appears unrelated to their provitamin A or antioxidant properties, since carotenoids with and without provitamin A activity increased levels of connexin43 mRNA and protein, whereas the antioxidants methyl-bixin and alpha-tocopherol were inactive. Among carotenoids, β-carotene and canthaxanthin have been identified as potent stimulators in the gap junction system. Gap junctions function as water-filled pores that allow the exchange of low molecular weight compounds, connecting the cytosol of neighboring cells. Canthaxanthin upregulates the connexin43 gene, which encodes a major gap junction protein, in a dose-dependent manner. This represents the first carotenoid-inducible gene described in mammals and is of theoretical interest in cancer chemoprevention, though all evidence to date is from cell culture.
In PC12 cells differentiated by nerve growth factor, treatment with canthaxanthin inhibited the release of TNF-α, IL-1, and IL-6, and also inhibited the activity of caspase-3. Canthaxanthin has shown partial neuroprotective activity in chemically induced rat adrenal medulla cell deaths at lower concentrations. However, the exact mechanisms by which canthaxanthin exerts its neuroprotective effects have not been fully elucidated.
Carotenoids, when ingested orally, accumulate in skin and subcutaneous fat, creating a yellow-orange hue. The bronzing effect is achieved through carotenoid deposition in the dermis and subcutaneous tissue. This is a purely physicochemical coloring effect — the carotenoid acts as a pigment depositing in lipid-rich skin compartments — and is distinct from melanin synthesis. It does not require or confer the UV protection associated with melanin.
EPP is a rare inherited disorder in which accumulation of protoporphyrin IX in the skin causes severe photosensitivity upon exposure to visible and long-wave UV light. Canthaxanthin has been the most formally studied in this indication, typically in combination with beta-carotene.
Taking canthaxanthin by mouth, with or without beta-carotene, seems to reduce rash, itching, or eczema caused by sensitivity to sunlight exposure in people with EPP. Doses studied in scientific research for EPP are 60 to 90 mg of canthaxanthin daily on average for three to five months per year.
Evidence quality: Studies without control groups suggested a treatment effect of oral treatment with canthaxanthin, but the real effect is uncertain. Assessment of treatment effect on photosensitivity in patients with EPP carries a high risk of bias since experienced photosensitivity varies with weather conditions, exposure pattern, and pigmentation. The available data are primarily from uncontrolled case series and open-label studies rather than randomized controlled trials. Controlled trials are described as important but challenging to conduct given the small patient population. Overall, the evidence is suggestive but methodologically weak; canthaxanthin is no longer considered a first-line treatment for EPP in most clinical guidelines, having been superseded by afamelanotide.
Canthaxanthin has been used for the treatment of vitiligo, a disorder in which the melanocytes cease to synthesize melanin and disappear from the involved areas. The rationale was that carotenoid deposition could cosmetically mask depigmented patches. Open-label studies have been conducted; however, evidence remains at the level of uncontrolled pilot data. The cosmetic effect is temporary and reverses when supplementation is discontinued. No robust randomized controlled trials have established efficacy for this indication.
Uses investigated include cutaneous lupus erythematosus, polymorphous light eruption, and psoriasis. Canthaxanthin is also used to reduce sun sensitivity caused by certain medications and other conditions, but there is no good scientific evidence to support these uses. Evidence for all of these non-EPP photosensitivity indications is limited to case reports and small, uncontrolled series. No high-quality controlled evidence exists.
Canthaxanthin has been used over-the-counter in high doses as an oral tanning agent. Carotenoids accumulate in skin and subcutaneous fat, creating a yellow-orange hue; however, both agents remain underresearched in human populations. The skin color produced is carotenodermia — an orange-yellow hue rather than true melanin-based tanning — and it does not confer meaningful UV protection. Limitations of the evidence include lack of standardized reporting across studies, variability in study outcomes, and limited long-term safety data.
It has been suggested that canthaxanthin, beta-carotene, and other carotenoids may inhibit carcinogenesis via antioxidant activity. Canthaxanthin has been shown to inhibit lipid peroxidation in liposomes. Canthaxanthin, which has often been included in animal experiments for comparative purposes having little or no provitamin A activity, also exhibits strong protective effects in certain in vitro chemoprevention models. Canthaxanthin and other carotenoids have also been studied for activity in cancer and Parkinson disease, although evidence is limited.
Evidence quality: The cancer chemopreventive data for canthaxanthin are entirely preclinical — derived from cell culture systems and animal models. There are no published human intervention trials specifically evaluating canthaxanthin's effect on cancer incidence or progression. Epidemiological data specific to canthaxanthin (separate from total carotenoid intake) are also absent. This area cannot be characterized as having established human evidence.
Canthaxanthin has powerful antioxidant properties and plays a role in lipid metabolism, neuroprotection, and immunomodulation. Mechanistic studies have demonstrated modulation of inflammatory cytokines in cell models, as described in Section 3.5. Carotenoids modulate immune responses by influencing lymphocyte proliferation, enhancing natural killer cell activity, and regulating the production of pro- and anti-inflammatory cytokines. However, these immunomodulatory effects have not been demonstrated for canthaxanthin in controlled human clinical trials. The evidence is preliminary and confined to in vitro and animal systems.
As noted in the mechanisms section, canthaxanthin has shown neuroprotective effects in cell culture (PC12 cells) and in rat models. The exact mechanisms by which canthaxanthin exerts its neuroprotective effects have not been fully elucidated. No human clinical trials on neurodegenerative disease have been conducted. Evidence quality: preclinical only.
The dosages below are stated strictly as reported in the cited sources and reflect study conditions rather than recommendations.
Past reports have concluded that this chemical does not carry genotoxic, reproductive, or carcinogenic risks and does not have allergic potential as an oral medication, and that the acceptable daily intake is 0.03 mg/kg/day. The conclusion of both JECFA and the EU Scientific Committee for Food was that canthaxanthin is safe for humans at the ADI. Recently (2010), the EFSA Panel on Food Additives reconfirmed the already-established ADI. Canthaxanthin is not an irritant to skin or eyes and it is unlikely to be a skin sensitiser.
The most extensively documented and clinically significant adverse effect of canthaxanthin in humans is retinal crystal deposition, termed canthaxanthin retinopathy.
The most well-documented adverse effect of canthaxanthin in humans is the formation of crystal-like deposits in the retina, known as "canthaxanthin retinopathy." These deposits are dose-dependent and have been observed in both humans (at doses >30 mg/day) and non-human primates given high doses over extended periods. Canthaxanthin retinopathy manifests as birefringent, yellow to red crystals in the macula.
Morphologically, there are red, birefringent, lipid-soluble crystals in the inner layers of the entire retina. They are particularly large and numerous perifoveally, where they are also clinically visible, but they also occur in a ring-shaped form peripherally and equatorially. The crystals are located in a spongy degeneration of the inner neuropil, where atrophy of the inner parts of the Müller cells was noticed. The compound isolated from the retina was identical with synthetic canthaxanthin according to mass and proton-resonance spectroscopy.
From the great number and size of the crystals on the one hand, and the relatively small amount of isolated canthaxanthin on the other, it was concluded that the crystals presumably represent a canthaxanthin-lipoprotein complex rather than pure canthaxanthin alone. It is thought that damage occurs at the level of the macular vascular system around areas of canthaxanthin-lipoprotein complex deposits. Vascular dysfunction may occur due to aggregation of these complexes in vessel lipid layers, which modify and disrupt lipid membrane properties.
Higher doses may result in toxicity, characterized by an asymptomatic ring of yellow-orange crystals in the macular region. It is more prevalent when there is underlying retinal disease or if the patient also takes beta-carotene supplements.
Clinical course and reversibility: Cessation of canthaxanthin ingestion appears to reverse the retinopathy, but the time until crystal disappearance is variable. Despite a usually favorable outcome, long-standing visual changes may occur. A statistically significant decrease in the number of retinal deposits was found after an observation period of 26 months. The deposits disappeared slowly, while some remained even seven years after canthaxanthin therapy was discontinued. In one long-term observational study, patients were asymptomatic and no functional defect related to canthaxanthin could be detected. The conclusion was that ingestion of canthaxanthin causes no long-term adverse effects in that particular cohort; however, this finding must be considered in the context of other reports of visual loss.
Case report of visual loss: An 84-year-old woman presented with a two-month history of worsening vision in both eyes. She had a 10-year history of canthaxanthin use for tanning, at variable dosages. Estimated total dosage was greater than 100 g. Cessation of canthaxanthin ingestion appeared to reverse the retinopathy, but the time until crystal disappearance is variable. Despite a usually favorable outcome, long-standing visual changes may occur.
When retinal crystals are seen on clinical examination, it is recommended that the patient discontinue the drug. The long-term effect is unknown; however, a study showed slow disappearance of the crystals over 20 years.
A case of aplastic anemia has been reported in association with canthaxanthin ingestion. This remains an isolated case report and a causal relationship has not been definitively established. Nonetheless, it warrants notation as a potential serious adverse event.
At high oral doses, canthaxanthin causes carotenodermia — a reversible yellow-orange discoloration of the skin — which is the intended effect in the tanning context but may be undesirable at excessive intakes. This effect is dose-dependent and reverses upon discontinuation.
In Germany, the office of the federal board of health refused the permit for oral tanning agents containing canthaxanthin in 1985. Use of canthaxanthin tanning products cannot be recommended because of unknown safety associated with long-term use; such products are no longer considered safe in many regulatory frameworks. Canthaxanthin is not approved for use in Australia and New Zealand. In the United States, canthaxanthin is approved as a color additive in animal feed but is not approved as a color additive in human food at the levels required for tanning. In the EU, its use in food is permitted at regulated levels under E161g, but its use as an oral tanning supplement above the ADI is not authorized.
Information regarding safety and efficacy in pregnancy and lactation is lacking. No adequate controlled studies in pregnant women have been conducted.
Canthaxanthin retinopathy is more prevalent when there is underlying retinal disease or if the patient also takes beta-carotene supplements. The co-administration of beta-carotene may potentiate retinal crystal formation. Because canthaxanthin is fat-soluble, its absorption is enhanced by co-administration with dietary fat; conversely, fat malabsorption syndromes or very low-fat diets may reduce its bioavailability. No formal drug-drug interaction studies have been published in peer-reviewed literature for canthaxanthin.
The overall evidence base for canthaxanthin as a human health supplement is characterized by the following:
Health conditions that Canthaxanthin may help support.
Body systems that Canthaxanthin may help support.
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