Canthaxanthin is a red and pink pigment that occurs naturally in both plants and animals, (39738).

Certain countries use canthaxanthin as a drug. Orobronze (canthaxanthin) is sold in Canada as a nonprescription drug for artificial tanning purposes as 30 mg oral capsules (5631,5633). Oral tanning preparations containing canthaxanthin have been found to be readily available to consumers in the United States through mail order and tanning salons despite warnings from the US Food and Drug Administration (FDA) (5635,5638). A combination product containing beta-carotene and canthaxanthin (Phenoro: 10 mg beta-carotene and 15 mg canthaxanthin) is used in Europe for treatment of photosensitivities associated with EPP (5637). Other combination products containing beta-carotene and canthaxanthin are manufactured (Carotinoid-N, Apotrin), but are not available in the US (1326,5628).

Orally, canthaxanthin is used to reduce photosensitivity associated with erythropoietic protoporphyria (EPP). It is also used for light-sensitive skin diseases including polymorphous light eruption (PMLE), drug-induced photosensitivity, and solar urticaria. It is also taken to produce an artificial suntan.

In foods, canthaxanthin is used as a food coloring additive and added to animal feed to enhance the color of chicken skins, egg yolks, salmon, and trout.

In manufacturing, canthaxanthin has been used in cosmetics and as a tablet excipient.

LIKELY SAFE ...when used orally in amounts commonly found in foods. Canthaxanthin has Generally Recognized as Safe (GRAS) status in the US (4912), but is not to exceed 30 mg per pint of liquid food or per pound of solid or semisolid food (5630).

LIKELY UNSAFE ...when used orally in large amounts, such as those used for artificial tanning purposes (5628,5629). Evidence suggests individuals taking a cumulative dose of 37 grams will have retinal changes 50% of the time, while those taking a total cumulative dose of 60 grams will demonstrate definite retinal changes upon examination (5636,5641). Reported retinal changes in patients being treated with canthaxanthin have included deposition of crystals around the macula of the retina (5636,5639,5641,5644,39692,39707,39708,39709), slowing of dark-adaptation curves, and decreased amplitudes in electroretinograms (1326,5632,5638). Deposition of retinal crystals appears dose related (5638). Altered eye function, decreased visual acuity (5639), and aplastic anemia (5635) have also been reported. Avoid using.

PREGNANCY AND LACTATION: POSSIBLY UNSAFE ...when consumed in doses to treat and reduce photosensitivities due to reported retinal changes with use (5632); avoid using. LIKELY UNSAFE ...when used orally in large amounts for artificial tanning purposes due to reported retinal changes with use (5639); avoid using.

•  Dermatologic

  Orally, large amounts of canthaxanthin can cause orange-brown coloration of the skin (5632,39713,39720,34657). Large amounts of canthaxanthin orally can cause dry and itchy skin (5634), urticaria, and welts (5637).

•  Gastrointestinal

  Orally, canthaxanthin can cause orange or brick-red discoloration of stools (5631,39713,34657). Large amounts of canthaxanthin orally can cause diarrhea, nausea, and stomach cramps (5634).

•  Hematologic

  Orally large amounts of canthaxanthin can cause aplastic anemia (5635). A fatal case of aplastic anemia (5635) associated with the ingestion of canthaxanthin for tanning purposes has been reported. The patient refused treatment with human blood products due to religious beliefs and died (5635,39717,39722).

•  Hepatic

  Orally, large amounts of canthaxanthin can cause hepatitis (5635).

•  Ocular/Otic

  Orally, canthaxanthin can cause gold and yellow crystalline deposits around the macula of the retina (5632,5635,5636,5638,5639,5640,5641,39692). The granules do not seem to impair vision, but might slightly impair dark adaptations (39704,100218). Granules slowly disappear when canthaxanthin is discontinued (1326,5639,39707,39732,39709,5636,5640,39708,39724,39692). Complete granule resolution might take up to 20 years (100218). Large doses of canthaxanthin have been associated with decreased visual acuity (5639) and diminished retinal sensitivity (5641).

• Adult

  Oral:

  General: The typical dose for artificial tanning is 120 mg per day for several days (5633).
  
  Erythropoietic protoporphyria (EPP): Canthaxanthin 60-90 mg daily on average for three to five months per year (5640).
  
  Cutaneous lupus erythematosus (CLE): Canthaxanthin and beta-carotene 75-250 mg daily for up to 9 months have been used (34652).
  
  Polymorphous light eruption (PMLE): A combination of canthaxanthin and beta-carotene 75-250 mg daily for up to 9 months have been used (34652,34657).
  
  Vitiligo: Four pills of a specific product (Carotinoid-N) containing canthaxanthin 35 mg and beta-carotene 25 mg per pill for 2 weeks followed by two pills of this product for an additional 2 weeks have been used (39715).
  
  

• Standardization & Formulation

  There is insufficient reliable information available about the standardization of canthaxanthin.

 VITAMIN A HYPERSENSITIVITY

 HEMOLYSIS ASSAY

 VITAMIN A ASSAYS

There is insufficient reliable information available about the toxicology of canthaxanthin.

Distribution: Canthaxanthin remains in the plasma several months after people stop ingesting it (39717,39722).

General: Canthaxanthin is a carotenoid that is found naturally and produced synthetically (5637). It is not a precursor of vitamin A, has no vitamin A activity, is highly lipid soluble (5635), and accumulates in fatty tissue (5632).

Anticancer effects: In vitro and animal studies suggest canthaxanthin may inhibit the growth and transformation of tumor cells (5642,5647,5648) by inducing the gap junctional communication between cells (5649). In preliminary clinical research, canthaxanthin with beta-carotene prevented the onset of second primary tumors in the lung, colon, urinary bladder, and head and neck (39691) and increased disease-free intervals in patients following radical removal of the primary tumors in organs such as the lung, breast, colon, and head and neck areas (39710,39700). However, antiproliferative effects were lacking in some in vitro and human studies (39683,39688,39687). Some of canthaxanthin's protective activities may come from its degradation products, including 4-oxo-retinoic acid, which enhances both GJC and expression of connexin43 mRNA (5649). Canthaxanthin may protect by directly inhibiting cell growth (39742), affecting retinoid signaling pathway products (39684), or being largely independent of conversion to retinoic acid, as is the case for beta-carotene (39727). Cell types (keratinocytes vs. fibroblasts) may differ in how they process canthaxanthin (39731).

Anti-inflammatory effects: In vitro, canthaxanthin inhibits prostaglandin PGE2 formation (39698).

Antioxidant effects: In vitro, phenoxy radicals effectively oxidized canthaxanthin (39736); canthaxanthin was found to effectively quench singlet molecular oxygen (32696), and canthaxanthin inhibited low-density lipoprotein (LDL) oxidation in human monocyte-macrophages in a concentration-dependent manner (39735). Ingesting canthaxanthin and beta-carotene together inhibited the appearance of canthaxanthin in plasma, chylomicrons, and very-low-density lipoprotein (VLDL) subfractions, but not in LDL (39739).

Dermatologic effects: Oral canthaxanthin is thought to color the skin by accumulating in the epidermis and subcutaneous fat tissue (5635). Evidence suggests canthaxanthin and other carotenoids protect against photosensitization due to their antioxidant activity against reactive oxygen species by deactivating electronically excited molecules or acting as chain-breaking agents (1326,5649). However, some evidence in vitro shows that canthaxanthin does not reduce oxidative damage in human skin cells (32665).

Ocular effects: Canthaxanthin, even at relatively low concentrations, has the ability to modify retinal lipid properties and membrane organization (39695). Limited and subtle differences in vision have been identified between participants ingesting canthaxanthin and those not (39704,5639,39707,39732,39709,5636,5640,39708,1326,34641,39692). After isolating a specific xanthophyll-binding protein or proteins, binding between canthaxanthin and a solubilized retinal xanthophyll-binding protein or proteins was found to be lacking; therefore, the role of canthaxanthin in protecting against age-related macular degeneration is unclear (39686).