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Scientific Name(s): Beta-carotene-4,4′-dione
Common Name(s): Canthaxanthin, Carophyll red, Food Orange 8, Roxanthin red 10, Tanning pill, Tanning tablet
Medically reviewed by Holevn.org. Last updated on Jan 16, 2020.
Clinical Overview
Use
Although they are not recommended for these uses, tanning tablets have been used to give skin a natural-looking tan, prevent photosensitivity in people with inherited erythropoietic protoporphyria, and in the treatment of vitiligo. Canthaxanthin and other carotenoids have been studied for activity in cancer and Parkinson disease, although evidence is limited.
Dosing
Various dosing regimens are available. Therefore, review manufacturers’ directions before using. Historically, a recommended maximum daily intake of canthaxanthin was 25 mg/kg. However, use of these products cannot be recommended because of unknown safety associated with long-term use.
Contraindications
No longer considered safe.
Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.
Interactions
None well documented.
Adverse Reactions
Some adverse effects reported with tanning tablets include discoloration of the stool, palms of the hands, and soles of the feet; GI discomfort; canthaxanthin-induced retinopathy; and at least 1 case of aplastic anemia. In short- and long-term animal studies, the LD50 for canthaxanthin in mice, rats, and dogs has been found to be greater than 10,000 mg/kg.
Toxicology
Both beta-carotene and canthaxanthin are classified as “Generally Recognized As Safe (GRAS)” substances by the FDA.
History
A variety of OTC tablets and capsules containing the pigments beta-carotene and canthaxanthin have been available for more than 20 years and have been promoted to give the consumer a natural-looking tan. In the United States, these pigments are approved as color additives for use in food and drugs; although they are unapproved for use as ingested agents intended to color the skin. However, consumers may obtain canthaxanthin from a variety of sources including mail-order houses and tanning salons as an “over-the-counter sun-tanning agent.” Due to safety concerns, the agent is no longer approved in Canada and Australia.1, 2, 3
Chemistry
Canthaxanthin is highly lipid soluble and is found in a variety of sources, including plants, mushrooms, bacteria, sea trout, algae, brine shrimp, crayfish, and bird feathers. The deep red-orange pigment is often the only color in tanning preparations and it is sometimes referred to as Food Orange 8, carophyll red, or roxanthin red 10. The pigment also is used to enhance the appearance of foods, such as pizza, barbecue and spaghetti sauces, soups, salad dressings, fruit drinks, baked goods, pudding, cheeses, and catsup.1, 2, 3
Uses and Pharmacology
Canthaxanthin is a derivative of beta-carotene; however, it is not a precursor of vitamin A. The tanning effect (orange to brownish color) is the result of canthaxanthin accumulation in the epidermis and subcutaneous fatty tissue. Canthaxanthin is not melanogenic, erythemic, or photosensitizing. Depending on the dose, canthaxanthin is deposited in the retina and liver; orange discoloration of plasma has been documented.1
The typical dietary intake of beta-carotene and canthaxanthin added during food manufacturing is 0.3 and 5.6 mg, respectively.4 A recommended maximum daily intake of canthaxanthin is 25 mg/kg.5 In monkeys, canthaxanthin concentrates preferentially in the liver and spleen.6
Antineoplastic effects
Epidemiologic evidence suggests that the incidence of cancers may be slightly lower among individuals with an above-average intake of beta-carotene and other carotenoids. These compounds may deactivate reactive chemical species, such as singlet oxygen and free radicals.7, 8 They also may have some slight pro-vitamin A effect that may contribute to the neoplastic protectant effect.9
Animal data
Mice supplemented with beta-carotene for 5 weeks prior to and 26 weeks after the administration of a nitrosamine derivative to induce bladder cancer developed fewer tumors than did unsupplemented mice. Mice receiving canthaxanthin showed no protection.10 Mice receiving canthaxanthin, retinyl palmitate, or a combination of both developed fewer cutaneous tumors following exposure to UV irradiation.11 Dietary supplementation of canthaxanthin inhibited the initiation of experimental breast tumors in mice but did not slow their spread.12 Evidence suggests canthaxanthin is able to induce apoptosis in tumor cells.13
Clinical data
Research reveals no clinical data regarding the use of tanning tablets as an antineoplastic. A review of the chemoprotective effects of carotenoids revealed that high doses of beta-carotene do not exhibit chemopreventive activity in clinical trials.14
An inverse association has been suggested for carotenoid intake and Parkinson disease based in animal and in vitro studies.15
Clinical trials have evaluated the role of micronutrient intake and the risk of Parkinson disease; however, insufficient data exist for carotenoids in this capacity.15
Dermatologic uses
Animal data
Research reveals no animal data regarding the use of tanning tablets for dermatologic use.
Clinical data
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. In an open study of 56 patients with vitiligo, patients were administered canthaxanthin for 20 days with dosages based on weight. Fifty-four percent of patients were not satisfied, 35% were satisfied, and 10% were very satisfied with the results of canthaxanthin pigmentation.1, 5
Porphyrias
Animal data
Research reveals no animal data regarding the use of tanning tablets in porphyrias.
Clinical data
Beta-carotene and canthaxanthin administration helped prevent photosensitivity in people with inherited erythropoietic protoporphyria. This skin disorder is characterized by burning, itching skin often with ulceration following exposure to sunlight. Beta-carotene effectively protects against photosensitivity but does not protect from UV-induced sunburn.4, 16
Tanning effects
Labeling for OTC products recommends taking several tablets a day for 2 to 3 weeks, then smaller periodic doses to maintain the coloration. The skin color accumulates over a 2-week period, then fades in about 2 weeks when the product is discontinued. Ingestion of too much pigment can make the palms of the hands turn orange.5 One brand of tablets contains 4 mg of beta-carotene and 36 mg of canthaxanthin per dose; the resulting daily intake of beta-carotene and canthaxanthin would be 12 to 16 mg and 108 to 144 mg, respectively.4 Ingestion of these large amounts of pigment results in the accumulation of dyes in adipose tissue with a resultant yellow discoloration of the skin. The “tan” has a distinct orange tinge and affords no protection against sunburn.5
Animal/Clinical data
Research reveals no animal or clinical data regarding the use of tanning tablets for tanning. See also Adverse Reactions and Toxicology.
Dosing
Various dosing regimens are available. Therefore, review manufacturers’ directions before using. Historically, a recommended maximum daily intake of canthaxanthin was 25 mg/kg. However, use of these products cannot be recommended because of unknown safety associated with long-term use.
Pregnancy / Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Interactions
None well documented.
Adverse Reactions
Some adverse effects reported with tanning tablets include discoloration of the stool, palms of the hands, and soles of the feet; GI discomfort; canthaxanthin-induced retinopathy17, 18; and at least 1 case of aplastic anemia. In short- and long-term animal studies, the LD50 for canthaxanthin in mice, rats, and dogs has been found to be greater than 10,000 mg/kg.5(5)
Toxicology
Beta-carotene and canthaxanthin are classified as generally recognized as safe (GRAS) substances by the FDA.8, 19 The conversion of beta-carotene to vitamin A is limited by physiologic requirements, and, therefore, the ingestion of these tablets does not pose a threat of hypervitaminosis A. Canthaxanthin is not metabolized to vitamin A in humans, and some question exists as to whether it may interfere with the conversion of carotene to vitamin A.4
In short- and long-term animal studies, the LD50 for canthaxanthin in mice, rats, and dogs has been found to be greater than 10,000 mg/kg.5, 8
A small amount of the drug is absorbed and large quantities are excreted in the feces, imparting a brick-red color to the stool, a side effect that may mask the presence of rectal bleeding.1, 5
There have been no reports of teratogenicity, carcinogenicity, or histotoxicity.5, 8 No toxicity was noted in volunteers who ingested 180 mg/day of beta-carotene for 10 weeks.20 These dyes afford no protection against sunburn, and patients should be instructed to take adequate precautions against exposure. Severe orange discoloration of plasma has been noted by blood collection agencies in blood samples obtained from subjects who ingested tanning tablets, although toxic levels of vitamin A were not found in the samples. Orange discoloration of the palms of the hands and soles of the feet also has been reported.1, 21, 22
The most common nondermatologic adverse effects include nausea, cramps, and diarrhea, which occurred in about one third of patients receiving these pigments as treatment for photosensitivity. The FDA has received reports of drug-induced hepatitis and a case of severe itching and welts that may have been related to oral tanning products.4
Amenorrhea has been reported among women receiving carotenoid therapy, although with a very low prevalence.23
In a survey of 50 patients who took more than 200 tanning tablets over a period of time, 12% found golden crystalline deposits in the inner layers of the retina and around the macula.24 Six of 51 patients ingesting 3.6 to 66 g of canthaxanthine within a 24-month period also developed deposits in the ocular fundus.25 In one case report, a patient sustained a branch retinal vein occlusion in the left eye believed to be associated with use of the drug.26 Decreased visual acuity was observed in some patients, but the long-term implications of these deposits are not understood. Deposits have been identified for up to 7 years after discontinuation of canthaxanthin.1, 27 Retinopathy does not appear to develop in patients taking beta-carotene alone.19
A woman 20 years of age died secondary to developing aplastic anemia after ingesting a course of high-dose canthaxanthin-containing tanning tablets. Although supportive measures may have saved the patient, her religious beliefs precluded the use of these interventions.28
References
1. Hulisz DT, Boles GL. Clinical review of canthaxanthin (tanning pills). Am Pharm. 1993;NS33(8):44-46.82134722. Levit F. Availability of canthaxanthin in the United States. J Am Acad Dermatol. 1985;12(1 pt 1):129.39202913. Windholz M, ed. Merck Index. 10th ed. Rahway, NJ: Merck;1983.4. Fenner L. The tanning pill, a questionable inside dye job. FDA Consumer. 1982;16:23.5. Gupta AK, Haberman HF, Pawlowski D, Shulman G, Menon IA. Canthaxanthin. Int J Dermatol. 1985;24(8):528-532.39340896. Mathews-Roth MM, Welankiwar S, Sehgal PK, Lausen NC, Russett M, Krinsky NI. Distribution of [14C] canthaxanthin and [14C] lycopene in rats and monkeys. J Nutr. 1990;120(10):1205-1213.21203987. Burton GW, Ingold KU. beta-carotene: an unusual type of lipid antioxidant. Science. 1984;224(4649):569-573.67101568. Esatbeyoglu T, Rimbach G. Canthaxanthin: From molecule to function. Mol Nutr Food Res. 2016 Sep 30. [Epub ahead of print]276876959. Bertram JS, Pung A, Churley M, Kappock TJ 4th, Wilkins LR, Cooney RV. Diverse carotenoids protect against chemically induced neoplastic transformation. Carcinogenesis. 1991;12(4):671-678.201313110. Mathews-Roth MM, Lausen N, Drouin G, Richter A, Krinsky NI. Effects of carotenoid administration on bladder cancer prevention. Oncology. 1991;48(3):177-179.190255911. Gensler HL, Aickin M, Peng YM. Cumulative reduction of primary skin tumor growth in UV-irradiated mice by the combination of retinyl palmitate and canthaxanthin. Cancer Lett. 1990;53(1):27-31.211882712. Grubbs CJ, Eto I, Juliana MM, Whitaker LM. Effect of canthaxanthin on chemically induced mammary carcinogenesis. Oncology. 1991;48(3):239-245.190256013. Palozza P, Maggiano N, Calviello G, et al. Canthaxanthin induces apoptosis in human cancer cell lines. Carcinogenesis. 1998;19(2):373-376.949829214. Tanaka T, Shnimizu M, Moriwaki H. Cancer chemoprevention by carotenoids. Molecules. 2012;17(3):3202-3242.2241892615. Takeda A, Nyssen OP, Syed A, Jansen E, Bueno-de-Mesquita B, Gallo V. Vitamin A and carotenoids and the risk of Parkinson’s disease: a systematic review and meta-analysis. Neuroepidemiology. 2014;42(1):25-38.2435606116. Wilson JD, et al. Harrison’s Principles of Internal Medicine. New York, NY: McGraw-Hill, Inc; 1991.17. Sujak A. Interactions between canthaxanthin and lipid membranes—possible mechanisms of canthaxanthin toxicity. Cell Mol Biol Lett. 2009;14(3):395-410.1921439418. Lamba N, Anderson-Nelson S. Medication induced retinal side effects. Dis Mon. 2014;60(6):263-267.2490667119. Herbert V. Canthaxanthin toxicity. Am J Clin Nutr. 1991;53(2):573-574.189917520. Mathews-Roth MM. Plasma concentrations of carotenoids after large doses of beta-carotene. Am J Clin Nutr. 1990;52(3):500-501.220325321. Rock GA, Decary F, Cole RS. Orange plasma from tanning capsules. Lancet. 1981;1(8235):1419-1420.611337222. Bareford D, Cumberpatch M, Derrick Tovey L. Plasma discolouration due to sun-tanning tablets. Vox Sang. 1984;46(3):180-182.642433323. Mathews-Roth MM. Amenorrhea associated with carotenemia. JAMA. 1983;250(6):731.687632824. Rousseau A. Canthaxanthine deposits in the eye. J Am Acad Dermatol. 1983;8(1):123-124.640252625. Boudreault G, Cortin P, Corriveau LA, Rousseau AP, Tardif Y, Malenfant M. Canthaxanthine retinopathy: 1. clinical study in 51 consumers [in French]. Can J Ophthalmol. 1983;18(7):325-328.642324626. Chang TS, Aylward GW, Clarkson JG, Gass JD. Asymmetric canthaxanthin retinopathy. Am J Ophthalmol. 1995;119(6):801-802.778570027. Bloomenstein MR, Pinkert RB. Canthaxanthine retinopathy. J Am Optom Assoc. 1996;67(11):690-692.897966328. Bluhm R, Branch R, Johnston P, Stein R. Aplastic anemia associated with canthaxanthin ingested for “tanning” purposes. JAMA. 1990;264(9):1141-1142.2117075
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This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.
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