Changes in plasma lipids and lipoproteins during isotretinoin therapy for acne.
Abstract
Abnormalities in plasma lipids are a recognized side effect of isotretinoin therapy for nodulocystic acne. We studied 60 patients during 20 weeks of isotretinoin therapy, to measure changes in plasma lipids and lipoproteins, to compare plasma lipid responses in men and women, and to determine whether there are alterations in levels of lipoprotein lipase or hepatic triglyceride lipase that could explain the development of isotretinoin-induced hypertriglyceridemia. Mean triglyceride levels rose in men and women, with maximum mean increases of 46.3 mg per deciliter (P less than 0.0001) and 52.3 mg per deciliter (P less than 0.002), respectively. The maximum level was reached by 4 weeks of therapy in men but not until the 12th week in women. Nine of 53 patients (17 per cent) completing 20 weeks of isotretinoin therapy acquired hypertriglyceridemia, with values of 200 to 600 mg per deciliter. Both men and women had significant increases in mean plasma levels of cholesterol and low-density-lipoprotein cholesterol and decreases in mean levels of high-density-lipoprotein cholesterol. There were no significant changes in mean levels of lipoprotein lipase or hepatic triglyceride lipase. Plasma lipid and lipoprotein levels returned to base line by eight weeks after discontinuation of the drug. If sustained over a long period, the change in the ratio of low-density-lipoprotein cholesterol to high-density-lipoprotein cholesterol that we observed, from 2.4 to 3.0 (P less than 0.0001), would predict an increased risk of cardiovascular disease.
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Retinoids such as isotretinoin and the anticancer drug bexarotene increase triglyceride levels.
“An increase in hepatic VLDL and apoC-III production and perhaps a decrease in LpL leading to increased triglyceride levels are also seen during use of retinoids such as isotretinoin and the anticancer drug bexarotene (110 -112).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [110]
Cites
Enzymatic determination of total serum cholesterol.
Allain, C. C., Poon, L. S., Chan, C. S. G., Richmond, W., & Fu, P. C. (1974) · Clinical Chemistry · doi:10.1093/clinchem/20.4.470 · Cited by 9,845 · see citing works
High density lipoprotein as a protective factor against coronary heart disease
Gordon, T., Castelli, W. P., Hjortland, M. C., Kannel, W. B., & Dawber, T. R. (1977) · The American Journal of Medicine · doi:10.1016/0002-9343(77)90874-9 · Cited by 5,059 · see citing works
Quantitative Determination of Serum Triglycerides by the Use of Enzymes
Bucolo, G., & David, H. (1973) · Clinical Chemistry · doi:10.1093/clinchem/19.5.476 · Cited by 3,202 · see citing works
Serum Lipoproteins and Coronary Heart Disease in a Population Study of Hawaii Japanese Men
Rhoads, G. G., Gulbrandsen, C. L., & Kagan, A. (1976) · New England Journal of Medicine · doi:10.1056/nejm197602052940601 · Cited by 876 · see citing works
Prolonged Remissions of Cystic and Conglobate Acne with 13-cis-Retinoic Acid
Peck, G. L., Olsen, T. G., Yoder, F. W., Strauss, J. S., Downing, D. T., Pandya, M. D., Butkus, D., & ARNAUD‐BATTANDIER, J. (1979) · New England Journal of Medicine · doi:10.1056/nejm197902153000701 · Cited by 519 · see citing works
Cholesterol in high-density lipoprotein: use of Mg2+/dextran sulfate in its enzymic measurement.
Finley, P. R., Schifman, R. B., Williams, R. J., & Lichti, D. A. (1978) · Clinical Chemistry · doi:10.1093/clinchem/24.6.931 · Cited by 418 · see citing works
Isotretinoin therapy for acne: results of a multicenter dose-response study
Strauss, J. S., Rapini, R. P., Shalita, A. R., Konecky, E., Pochi, P. E., Comite, H., & Exner, J. H. (1984) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(84)80100-0 · Cited by 223 · see citing works
Isotretinoin versus placebo in the treatment of cystic acne
Peck, G. L., Olsen, T. G., Butkus, D., Pandya, M., Arnaud-Battandier, J., Gross, E. G., Windhorst, D. B., & Cheripko, J. (1982) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(82)70063-5 · Cited by 179 · see citing works
General clinical toxicology of oral retinoids
Windhorst, D. B., & Nigra, T. P. (1982) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(82)70056-8 · Cited by 158 · see citing works
Isotretinoin treatment of acne and related disorders: An update
Shalita, A. R., Cunningham, W. J., Leyden, J. J., Pochi, P. E., & Strauss, J. S. (1983) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(83)70176-3 · Cited by 133 · see citing works
A dose-response study of 13-cis-retinoic acid in acne vulgaris
Jones, D. H., KING, K., MIILER, A. J., & Cunliffe, W. J. (1983) · British Journal of Dermatology · doi:10.1111/j.1365-2133.1983.tb03973.x · Cited by 125 · see citing works
Pharmacokinetics of the retinoids isotretinoin and etretinate
Brazzell, R. K., & Colburn, W. A. (1982) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(82)70053-2 · Cited by 119 · see citing works
Baginsky, M. L., & Brown, W. V. (1979) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)40610-8 · Cited by 110 · see citing works
Self-citationChanges in Plasma Cholesterol and Triglyceride Levels After Treatment With Oral Isotretinoin
Zech, L. A. (1983) · Archives of Dermatology · doi:10.1001/archderm.119.12.987 · Cited by 82 · see citing works
Elevation of Serum Triglyceride Levels From Oral Isotretinoin in Disorders of Keratinization
Katz, R. A. (1980) · Archives of Dermatology · doi:10.1001/archderm.1980.01640360043015 · Cited by 79 · see citing works
Eruptive Xanthomas Associated With Isotretinoin (13-Cis-Retinoic Acid)
Dicken, C. H. (1980) · Archives of Dermatology · doi:10.1001/archderm.1980.01640320101023 · Cited by 78 · see citing works
Ward, A., Brogden, R. N., Heel, R. C., Speight, T. M., & Avery, G. S. (1983) · Drugs · doi:10.2165/00003495-198326010-00002 · Cited by 75 · see citing works
Effect of oral 13-cis-retinoic acid on serum lipids
LYONS, F., Laker, M. F., Marsden, J. R., MANUEL, R., & Shuster, S. (1982) · British Journal of Dermatology · doi:10.1111/j.1365-2133.1982.tb00411.x · Cited by 72 · see citing works
Etretinate Therapy Causes Increases in Lipid Levels in Patients With Psoriasis
Ellis, C. N. (1982) · Archives of Dermatology · doi:10.1001/archderm.1982.01650200027010 · Cited by 55 · see citing works
Changes in lipid metabolism during retinoid administration
Gerber, L. E., & Erdman, J. W. (1982) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(82)80047-9 · Cited by 43 · see citing works
Treatment of common lipoprotein disorders.
Brown, W., Goldberg, I. J., & Ginsberg, H. N. (1984) · Progress in cardiovascular diseases · doi:10.1016/0033-0620(84)90017-3 · Cited by 30 · see citing works
Self-citationElevation of Blood Triglyceride Levels Secondary to Administration of Vitamin A
Dicken, C. H. (1981) · Archives of Dermatology · doi:10.1001/archderm.1981.01650040003003 · Cited by 24 · see citing works
Gollnick, H. P. M., Tsambaos, D., & Orfanos, C. E. (1981) · Archives of Dermatological Research · doi:10.1007/bf00412546 · Cited by 20 · see citing works
Gollnick, H. P. M. (1981) · Springer eBooks · doi:10.1007/978-3-642-68023-6_81 · Cited by 13 · see citing works
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Sorted by citations
Guidelines of care for the management of acne vulgaris
Zaenglein, A. L., Pathy, A. L., Schlosser, B. J., Alikhan, A., Baldwin, H. E., Berson, D. S., Bowe, W. P., Graber, E. M., Harper, J. C., Kang, S., et al. (2016) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2015.12.037 · Cited by 1,597 · see citing works
Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline
Berglund, L., Brunzell, J. D., Goldberg, A. C., Goldberg, I. J., Sacks, F., Murad, M. H., & Stalenhoef, A. F. H. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-3213 · Cited by 887 · see citing works
Drug-Induced Acute Pancreatitis: An Evidence-Based Review
Badalov, N. L., Baradarian, R., Iswara, K., Li, J., Steinberg, W. M., & Tenner, S. M. (2007) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2006.11.023 · Cited by 587 · see citing works
Guidelines of care for acne vulgaris management
Strauss, J. S., Krowchuk, D. P., Leyden, J. J., Lucky, A. W., Shalita, A. R., Siegfried, E. C., Thiboutot, D. M., Voorhees, A. S. V., Beutner, K. A., Sieck, C. K., et al. (2007) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2006.08.048 · Cited by 552 · see citing works
Issues in Hyperlipidemic Pancreatitis
Yadav, D. K., & Pitchumoni, C. S. (2003) · Journal of Clinical Gastroenterology · doi:10.1097/00004836-200301000-00016 · Cited by 435 · see citing works
Serum Retinol Levels and the Risk of Fracture
Michaëlsson, K., Lithell, H., Vessby, B. O., & Melhus, H. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa021171 · Cited by 371 · see citing works
Toskes, P. P. (1990) · Gastroenterology Clinics of North America · doi:10.1016/s0889-8553(21)00513-6 · Cited by 337 · see citing works
Okamura, T., Tsukamoto, K., Arai, H., Fujioka, Y., Ishigaki, Y., Koba, S., Ohmura, H., Shoji, T., Yokote, K., Yoshida, H., et al. (2023) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.gl2022 · Cited by 317 · see citing works
A review of diagnosis and treatment of acne in adult female patients
Tan, A. U., Schlosser, B. J., & Paller, A. S. (2017) · International Journal of Women’s Dermatology · doi:10.1016/j.ijwd.2017.10.006 · Cited by 263 · see citing works
“Routine monitoring of serum lipid profiles and liver function studies are recommended to be done regularly but the interval varies (Bershad et al., 1985; Lammer et al., 1985; Leachman et al., 1999; McElwee et al., 1991; Zech et al., 1983).”
BackgroundQuantitative Profiling of Endogenous Retinoic Acid in Vivo and in Vitro by Tandem Mass Spectrometry
Kane, M. A., Folias, A. E., Wang, C., & Napoli, J. L. (2008) · Analytical Chemistry · doi:10.1021/ac702030f · Cited by 230 · see citing works
Lipid metabolism in mammalian tissues and its control by retinoic acid
Bonet, M. L., Ribot, J., & Palou, A. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.06.001 · Cited by 212 · see citing works
Secondary causes of hyperlipidemia.
Stone, N. J. (1994) · Medical Clinics of North America · doi:10.1016/s0025-7125(16)30179-1 · Cited by 199 · see citing works
Akhavan, A., & Bershad, S. V. (2003) · American Journal of Clinical Dermatology · doi:10.2165/00128071-200304070-00004 · Cited by 185 · see citing works
“[86] Rarer adverse ef- range of 3–10μm, to deliver the drug preferentially into the follicufects include pseudotumor cerebri,[87] hyperostosis,[88,89] hepato- lar duct, with minimal penetration into the epidermis.”
BackgroundSelf-citationZane, L. T., Leyden, W. A., Marqueling, A. L., & Manos, M. M. (2006) · Archives of Dermatology · doi:10.1001/archderm.142.8.1016 · Cited by 183 · see citing works
“6% to 32%.(8,9,11,12) Limited sample sizes diminish the precision of these studies’ estimates, and the lack of standard criteria for defining abnormal values among these studies makes them difficult to compare.”
BackgroundOral retinoid therapy for dermatologic conditions in children and adolescents
Brecher, A. R., & Orlow, S. J. (2003) · Journal of the American Academy of Dermatology · doi:10.1067/s0190-9622(03)01564-0 · Cited by 158 · see citing works
Quantification of Endogenous Retinoids
Kane, M. A., & Napoli, J. L. (2010) · Methods in molecular biology · doi:10.1007/978-1-60327-325-1_1 · Cited by 154 · see citing works
Vu-Dac, N., Gervois, P., Torra, I. P., Fruchart, J. C., Kosykh, V, Kooistra, T., Princen, H. M., Dallongeville, J., & Staels, B. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1581 · Cited by 143 · see citing works
“First, the retinoid-induced hypertriglyceridemia in humans appears primarily of hepatic origin, whereas in rodents retinoids may act both by increasing hepatic VLDL synthesis, reducing hepatic VLDL uptake and decreasing peripheral lipolysis due to lowered LPL activity (52, 53).”
BackgroundInfluentialModulation of RXR function through ligand design
Pérez, E., Bourguet, W., Gronemeyer, H., & de Lera, A. R. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.04.003 · Cited by 169 · see citing works
David, M., Hodak, E., & Lowe, N. J. (1988) · Medical Toxicology · doi:10.1007/bf03259940 · Cited by 135 · see citing works
Olsén, T., & Blomhoff, R. (2019) · Advances in Nutrition · doi:10.1093/advances/nmz131 · Cited by 126 · see citing works
“One common side effect of isotretinoin treatment is dyslipidemia (31, 32) as well as elevation of plasma total homocysteine concentration as recently reviewed (33).”
BackgroundMelnik, B. C. (2017) · Acta Dermato Venereologica · doi:10.2340/00015555-2535 · Cited by 131 · see citing works
Mantel-Teeuwisse, A. K., Kloosterman, J. M. E., der Zee, A. H. M., Klungel, O. H., Porsius, A. J., & de Boer, A. (2001) · Drug Safety · doi:10.2165/00002018-200124060-00003 · Cited by 126 · see citing works
“fects[67,72,74] as well as decreases[66,68,69,73] have been reported.”
BackgroundLaboratory Monitoring During Isotretinoin Therapy for Acne: A Systematic Review and Meta-analysis
Lee, Y. H., Scharnitz, T. P., Muscat, J., Chen, A., Gupta-Elera, G., & Kirby, J. S. (2016) · JAMA Dermatology · doi:10.1001/jamadermatol.2015.3091 · Cited by 120 · see citing works
A Comprehensive Update on the Chylomicronemia Syndrome
Goldberg, R. B., & Chait, A. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.593931 · Cited by 121 · see citing works
Rodondi, N., Darioli, R., Ramelet, A., Hohl, D., Lenain, V., Perdrix, J., Wietlisbach, V., Riesen, W. F., Walther, T., Medinger, L., et al. (2002) · Annals of Internal Medicine · doi:10.7326/0003-4819-136-8-200204160-00007 · Cited by 111 · see citing works
“The clinical chemistry laboratory of Lausanne University Medical Policlinic performed bio- Context Isotretinoin (Accutane, Roche, Basel, Switzerland) is the treatment of choice for severe acne that is resistant to topical treatment.”
BackgroundChanges in Plasma Lipids and Lipoproteins during Isotretinoin Therapy for Acne
Weber, D. J., Rutala, W. A., Samsa, G. P., Bradshaw, S. E., & Lemon, S. M. (1986) · New England Journal of Medicine · doi:10.1056/nejm198605223142120 · Cited by 104 · see citing works
Acquired Hyperlipidemia (Secondary Dyslipoproteinemias)
Chait, A., & Brunzell, J. D. (1990) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(18)30324-4 · Cited by 101 · see citing works
Henkin, Y. (1992) · JAMA · doi:10.1001/jama.1992.03480070077035 · Cited by 99 · see citing works
Recent Advances in Dermatology
Phillips, T. J., & Dover, J. S. (1992) · New England Journal of Medicine · doi:10.1056/nejm199201163260305 · Cited by 95 · see citing works
Barth, J. H., MacDonald-Hull, S. P., Mark, J. J., Jones, R. G., & Cunliffe, W. J. (1993) · British Journal of Dermatology · doi:10.1111/j.1365-2133.1993.tb03336.x · Cited by 94 · see citing works
The Roles of Vitamin A in the Regulation of Carbohydrate, Lipid, and Protein Metabolism
Chen, W., & Chen, G. (2014) · Journal of Clinical Medicine · doi:10.3390/jcm3020453 · Cited by 93 · see citing works
“Medical administration of isotretinoin (13-cis RA) results in hypertriglyceridemia in human subjects with acne [87].”
BackgroundFoxO1 – the key for the pathogenesis and therapy of acne?
Melnik, B. C. (2010) · JDDG Journal der Deutschen Dermatologischen Gesellschaft · doi:10.1111/j.1610-0387.2010.07344.x · Cited by 90 · see citing works
Metabolic Effects of Rexinoids: Tissue-Specific Regulation of Lipoprotein Lipase Activity
Davies, P. J. A., Berry, S. A., Shipley, G. L., Eckel, R. H., Hennuyer, N., Crombie, D. L., Ogilvie, K. M., Peinado-Onsurbe, J., Fievet, C., Leibowitz, M. D., et al. (2001) · Molecular Pharmacology · doi:10.1124/mol.59.2.170 · Cited by 89 · see citing works
“, 1996) and humans (Lyons et al., 1982; Bershad et al., 1985) often results in increases in serum triglyceride levels.”
Gonzalez‐Soto, M., & Mutch, D. M. (2020) · Advances in Nutrition · doi:10.1093/advances/nmaa142 · Cited by 88 · see citing works
Cai, S., He, H., Nguyen, T., Mennone, A., & Boyer, J. L. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m005546 · Cited by 85 · see citing works
Rational therapy for acne vulgaris: An update on topical treatment
Leyden, J. J., & Shalita, A. R. (1986) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(86)70250-8 · Cited by 79 · see citing works
Ooi, L. Y., Walker, B. R., Bodkin, P. A., & Whittle, I. R. (2008) · British Journal of Neurosurgery · doi:10.1080/02688690701827340 · Cited by 74 · see citing works
The Endocrine Effects of Nonhormonal Antineoplastic Therapy
Yeung, S. J., Chiu, A. C., Vassilopoulou‐Sellin, R., & Gagel, R. F. (1998) · Endocrine Reviews · doi:10.1210/edrv.19.2.0328 · Cited by 72 · see citing works
Secondary dyslipidemia: its treatments and association with atherosclerosis
Yanai, H., & Yoshida, H. (2020) · Global Health & Medicine · doi:10.35772/ghm.2020.01078 · Cited by 71 · see citing works
“Hypertriglyceridemia is a metabolic complication of systemic retinoid therapy, which may occur in up to 17% of individuals treated with such therapy (92).”
BackgroundSide effects of common acne treatments
Tripathi, S. V., Gustafson, C. J., Huang, K. E., & Feldman, S. R. (2013) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2013.740456 · Cited by 70 · see citing works
“Nine of 53 patients (17 percent) completing 20 weeks of isotretinoin therapy acquired hypertriglyceridemia, with values of 200 to 600 mg per deciliter [87].”
BackgroundMelnik, B. C. (2011) · Dermato-Endocrinology · doi:10.4161/derm.15331 · Cited by 92 · see citing works
Pancreatitis Associated with Isotretinoin-lnduced Hypertriglyceridemia
Flynn, W. J., FREEMAN, P. G., & WICKBOLDT, L. G. (1987) · Annals of Internal Medicine · doi:10.7326/0003-4819-107-1-63 · Cited by 67 · see citing works
The effect of isotretinoin on triglycerides and liver aminotransferases
Vieira, A. S., Beijamini, V., & Melchiors, A. C. (2012) · Anais Brasileiros de Dermatologia · doi:10.1590/s0365-05962012000300005 · Cited by 65 · see citing works
“However, the alterations in the lipid profile of these patients induced by isotretinoin appear to be transitory, since they return to baseline levels approximately eight weeks after the end of treatment.(22) In addition, when using the total cholesterol/HDL cholesterol ratio to estimate cardiovascular risk, although a…”
BackgroundStrauss, J. S., Leyden, J. J., Lucky, A. W., Lookingbill, D. P., Drake, L. A., Hanifin, J. M., Lowe, N. J., Jones, T. M., Stewart, D. M., Jarratt, M., et al. (2001) · Journal of the American Academy of Dermatology · doi:10.1067/mjd.2001.115966 · Cited by 64 · see citing works
Retinoid-Induced Hypertriglyceridemia in Rats Is Mediated by Retinoic Acid Receptors
Standeven, A. M. (1996) · Fundamental and Applied Toxicology · doi:10.1006/faat.1996.0164 · Cited by 64 · see citing works
“13-c/s-RA was chosen for this experiment because it has been shown previously to cause hypertriglyceridemia in humans and in rats (Bershad et al., 1985; Gustafson et al., 1990).”
BackgroundMethodInitial clinical trial of the retinoid receptor pan agonist 9-cis retinoic acid.
Miller, V. A., Rigas, J. R., Benedetti, F. M., Verret, A. L., Tong, W. P., Kris, M. G., Gill, G. M., Loewen, G. R., Truglia, J. A., Ulm, E. H., et al. (1996) · PubMed · Cited by 63 · see citing works
Systemic retinoids in chemoprevention of non-melanoma skin cancer
Lens, M. B., & Medenica, L. (2008) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.9.8.1363 · Cited by 62 · see citing works
“A decrease in HDL and an increase in LDL was detected in some patients [81,82] .”
BackgroundMetabolic syndrome and skin: Psoriasis and beyond
Padhi, T., & Garima (2013) · Indian Journal of Dermatology · doi:10.4103/0019-5154.113950 · Cited by 62 · see citing works
“…ROS through sebum results in an increased blood level of circulating lipids and cholesterol, thereby increasing the risk of dyslipidemia and Met S. [14-16] The various components of Met S show seasonal variations in their symptoms and signs: Both blood pressure and blood cholesterol levels are…”
Isotretinoin and FoxO1: A scientific hypothesis.
Melnik, B. C. (2011) · Europe PMC (PubMed Central) · doi:10.4161/derm.3.3.15331 · Cited by 62 · see citing works
DRUGS CAUSING DYSLIPOPROTEINEMIA
Donahoo, W. T., Kosmiski, L. A., & Eckel, R. H. (1998) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(05)70033-5 · Cited by 62 · see citing works
The skin function: a factor of anti-metabolic syndrome
Zhou, S., Li, D., Zhou, Y., & Cao, J.-M. (2012) · Diabetology & Metabolic Syndrome · doi:10.1186/1758-5996-4-15 · Cited by 91 · see citing works
“In fact, numerous studies have found that long-term medication-induced inhibition of sebum secretion can lead to significant increases in the levels of lipids and cholesterol in the circulation, and consequently increase the risk of MetS [91] and atherosclerosis [65,66].”
BackgroundInfluentialSafety issues in isotretinoin therapy
Hanson, N., & Leachman, S. A. (2001) · Seminars in Cutaneous Medicine and Surgery · doi:10.1053/sder.2001.28209 · Cited by 59 · see citing works
Redlich, C. A., Chung, J. S., Cullen, M. R., Blaner, W. S., van Bennekum, A. M., & Berglund, L. (1999) · Atherosclerosis · doi:10.1016/s0021-9150(99)00266-x · Cited by 58 · see citing works
Management of Hypertriglyceridemia
Labossiere, R., & Goldberg, I. J. (2007) · Humana Press eBooks · doi:10.1007/978-1-59745-533-6_10 · Cited by 55 · see citing works
Isotretinoin: controversies, facts, and recommendations
Bauer, L. B., Ornelas, J. N., Elston, D. M., & Alikhan, A. (2016) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2016.1213629 · Cited by 54 · see citing works
The modern age of acne therapy: a review of current treatment options.
Bershad, S. V. (2001) · PubMed · Cited by 54 · see citing works
Self-citationRetinoids in Cancer Chemoprevention
COSTA, A., Palo, G. D., DeCensi, A., Formelli, F., Chiesa, F., Nava, M. B., Camerini, T., Marubini, E., & Veronesi, U. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb12118.x · Cited by 54 · see citing works
Dyslipidemia in dermatological disorders
Shenoy, M., Shenoy, C., & Rao, G. (2015) · North American Journal of Medical Sciences · doi:10.4103/1947-2714.168657 · Cited by 53 · see citing works
“Hypertriglyceridemia is a metabolic complication of systemic retinoid therapy, which may occur in up to 17% of people.[29] Apo C-III appears to be a target gene for retinoids acting via retinoid X receptor.”
BackgroundRoles of vitamin A status and retinoids in glucose and fatty acid metabolism
Zhao, S., Li, R., Yang, L., Chen, W., Zhang, Y., & Chen, G. (2012) · Biochemistry and Cell Biology · doi:10.1139/o11-079 · Cited by 52 · see citing works
Toxicity of Retinoids in Humans and Animals
Howard, W. B., & Willhite, C. C. (1986) · Journal of Toxicology Toxin Reviews · doi:10.3109/15569548609012706 · Cited by 52 · see citing works
O’Donnell, J. S. (2003) · American Journal of Therapeutics · doi:10.1097/00045391-200303000-00012 · Cited by 51 · see citing works
“Whereas transitory abnormal elevations in serum transaminases are rare, hyperlipidemia is frequent, with 25% of patients developing increased triglyceride levels and, less frequently, increased cholesterol and low-density lipoproteins and decreased high-density lipoproteins.(47) Myalgia and arthralgia are common compl…”
BackgroundRetinol-binding protein-4 in experimental and clinical metabolic disease
von Eynatten, M., & Humpert, P. M. (2008) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.8.3.289 · Cited by 49 · see citing works
Lawrence, J. A., Adamson, P. C., Caruso, R. C., Chow, C., Kleiner, D. E., Murphy, R. F., Venzon, D. J., Shovlin, M., Noone, M., Merino, M. J., et al. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.10.2754 · Cited by 49 · see citing works
Li, R., Chen, W., Li, Y., Zhang, Y., & Chen, G. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.02.031 · Cited by 48 · see citing works
Zhang, Y., Li, R., Yang, L., Chen, W., Zhao, S., & Chen, G. (2012) · Biochemistry and Cell Biology · doi:10.1139/o2012-012 · Cited by 46 · see citing works
All-trans retinoic acid regulates hepatic bile acid homeostasis
Yang, F., He, Y., Liu, H., Tsuei, J., Jiang, X., Yang, L., Wang, Z., & Wan, Y. Y. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.08.018 · Cited by 46 · see citing works
“Likewise, hypertriglyceridemia is common in patients who receive retinoid treatment for dermatological disorders [11].”
BackgroundVitamin paradox in obesity: Deficiency or excess?
Zhou, S. (2015) · World Journal of Diabetes · doi:10.4239/wjd.v6.i10.1158 · Cited by 40 · see citing works
Futoryan, T., & Gilchrest, B. A. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1994.tb01461.x · Cited by 41 · see citing works
Chen, G. (2021) · Cells · doi:10.3390/cells10082160 · Cited by 40 · see citing works
“When patients with acne are treated with 13-cis RA (isotretinoin), some of them develop hypertriglyceridemia [72].”
BackgroundErturan, İ., Nazıroğlu, M., & Akkaya, V. B. (2012) · Cell Biochemistry and Function · doi:10.1002/cbf.2830 · Cited by 40 · see citing works
Zhang, Y., Li, R., Chen, W., Li, Y., & Chen, G. (2011) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-011-0831-4 · Cited by 39 · see citing works
“When isotretinoin, 13-cis RA, was administered to treat patients with acne, some of them developed isotretinoin-induced hypertriglyceridemia [11].”
BackgroundIsotretinoin systemic therapy and the shadow cast upon dermatology's downtrodden hero
Lowenstein, E. B., & Lowenstein, E. J. (2011) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2011.08.026 · Cited by 38 · see citing works
Yu, J. N., Cunningham, J. A., Thouin, S. R., Gurvich, T., & Liu, D. (2000) · Primary Care Clinics in Office Practice · doi:10.1016/s0095-4543(05)70164-0 · Cited by 38 · see citing works
Lipid metabolism and retinoid therapy
Marsden, J. R. (1989) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(89)90074-0 · Cited by 37 · see citing works
No skin off your back: the sampling and extraction of sebum for metabolomics
Géhin, C., Tokarska, J., Fowler, S. J., Barran, P. E., & Trivedi, D. K. (2023) · Metabolomics · doi:10.1007/s11306-023-01982-3 · Cited by 37 · see citing works
“, 1970), and that inhibition of sebum production using isotretinoin resulted in significantly increased plasma triacylglycerol and cholesterol levels (Bershad et al., 1985; Zech et al., 1983).”
BackgroundEffects of long-term intake of retinol on selected clinical and laboratory indexes
Cartmel, B., Moon, T. E., & Levine, N. (1999) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/69.5.937 · Cited by 36 · see citing works
Ayaori, M., Yakushiji, E., Ogura, M., Nakaya, K., Hisada, T., Uto‐Kondo, H., Takiguchi, S., Terao, Y., Sasaki, M., Komatsu, T., et al. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2012.02.004 · Cited by 34 · see citing works
Side Effects and Long-term Toxicity of Synthetic Retinoids
Yob, E. H. (1987) · Archives of Dermatology · doi:10.1001/archderm.1987.01660340137036 · Cited by 34 · see citing works
McElwee, N. E. (1991) · Archives of Dermatology · doi:10.1001/archderm.1991.01680030061007 · Cited by 34 · see citing works
Hypertriglyceridemia-Associated Drug-Induced Acute Pancreatitis
Elkhouly, M. A., Salazar, M. J., & Simons-Linares, C. R. (2018) · Pancreas · doi:10.1097/mpa.0000000000001190 · Cited by 32 · see citing works
Amichai, B., & Grunwald, M. H. (2000) · Journal of Dermatological Treatment · doi:10.1080/095466300750134214 · Cited by 32 · see citing works
The link between Hepatic Vitamin A Metabolism and Nonalcoholic Fatty Liver Disease
Chen, G. (2015) · Current Drug Targets · doi:10.2174/1389450116666150325231015 · Cited by 32 · see citing works
Standeven, A. M., Thacher, S. M., Yuan, Y.-D., Escobar, M., Vuligonda, V., Beard, R. L., & Chandraratna, R. A. S. (2001) · Biochemical Pharmacology · doi:10.1016/s0006-2952(01)00803-6 · Cited by 32 · see citing works
RXR–LXR heterodimer modulators for the potential treatment of dyslipidemia
Lagu, B. R., Pio, B. A., Lebedev, R., Yang, M., & Pelton, P. D. (2007) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2007.01.047 · Cited by 31 · see citing works
Šedová, L., Šeda, O., Krenová, D., Křen, V., & Kazdová, L. (2004) · International Journal of Obesity · doi:10.1038/sj.ijo.0802613 · Cited by 31 · see citing works
Berthou, L., Staels, B., Saldicco, I., Berthelot, K., Casey, J., Fruchart, J., Denèfle, P., & Branellec, D. (1994) · Arteriosclerosis and Thrombosis A Journal of Vascular Biology · doi:10.1161/01.atv.14.10.1657 · Cited by 31 · see citing works
“In humans, treatment with vitamin A derivatives was shown to be associated with a similar increase in serum trigh/cerides, whereas plasma apoA-I did not change substantially.(52)-(55) In contrast to the situation observed in humans and rats, plasma apoA-I concentrations have been reported to increase in rabbits on tre…”
BackgroundFarhangi, M. A., Keshavarz, S. A., Eshraghian, M., Ostadrahimi, A., & Saboor-Yaraghi, A. A. (2012) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1258/acb.2012.012096 · Cited by 30 · see citing works
Cisneros, F. J., Gough, B., Patton, R. E., & Ferguson, S. A. (2005) · Journal of Applied Toxicology · doi:10.1002/jat.1082 · Cited by 30 · see citing works
“One of these side effects is increased cholesterol levels (Lyons et al., 1982; Zech et al., 1983; Marsden et al., 1984; Bershad et al., 1985; Michaelsson et al., 1986; Barth et al., 1993; Fex et al., 1996; Ostlere et al., 1996; Lestringant et al., 1997).”
BackgroundInfluentialStoll, D., Binnert, C., Mooser, V., & Tappy, L. (2003) · Metabolism · doi:10.1016/j.metabol.2003.07.006 · Cited by 30 · see citing works
BREATHNACH, S. M. (2010) · Wiley eBooks · doi:10.1002/9781444317633.ch75 · Cited by 31 · see citing works
Mamoon, A. M., Subauste, A. R., Subauste, M. C., & Subauste, J. S. (2014) · Gene · doi:10.1016/j.gene.2014.07.017 · Cited by 29 · see citing works
Lestringant, G. G., Frossard, P. M., Agarwal, M., & Galadari, I. H. (1997) · International Journal of Dermatology · doi:10.1046/j.1365-4362.1997.00331.x · Cited by 29 · see citing works
Kaptein, A., de Wit, E. C., & Princen, H. M. G. (1993) · Arteriosclerosis and Thrombosis A Journal of Vascular Biology · doi:10.1161/01.atv.13.10.1505 · Cited by 29 · see citing works
Low‐dose retinoid therapy for chemoprophylaxis of skin cancer in renal transplant recipients
Gibson, G. E., O’Grady, A., Kay, E. W., & Murphy, G. M. (1998) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/j.1468-3083.1998.tb00926.x · Cited by 28 · see citing works
Genetically personalised organ-specific metabolic models in health and disease
Foguet, C., Xu, Y., Ritchie, S. C., Lambert, S. A., Persyn, E., Nath, A. P., Davenport, E. E., Roberts, D. J., Paul, D. S., Angelantonio, E. D., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-35017-7 · Cited by 27 · see citing works
Influence of apolipoprotein E polymorphism on plasma vitamin A and vitamin E levels
Gómez‐Coronado, D., Bueno, A. E., Álvarez, J. J., Ortega, H., Olmos, J. M., Castro, M., Sastre, A., Herrera, E., & Lasunción, M. A. (2002) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2002.00983.x · Cited by 27 · see citing works
The Effect of Vitamin A Supplementation on Biochemical Parameters in Multiple Sclerosis Patients
Jafarirad, S., Siassi, F., Harirchian, M.-H., Amani, R., Bitarafan, S., & Saboor-Yaraghi, A.-A. (2013) · Iranian Red Crescent Medical Journal · doi:10.5812/ircmj.3480 · Cited by 27 · see citing works
“Despite this insignificant difference, cholesterol and TG reduction in these patients have been positive unexpected results (19) since in other studies on isotretinoin, etretinate, and other metabolites of vitamin A, higher levels of cholesterol and TG were observed in pharmacologic dosage of vitamin A supplement (20-…”
ResultLow-dose retinoid therapy for chemoprophylaxis of skin cancer in renal transplant recipients.
Gibson, G. E., O’Grady, A., Kay, E. W., & Murphy, G. M. (1998) · PubMed · Cited by 27 · see citing works
RETRACTION: All-Trans-Retinoic Acid Enhances Mitochondrial Function in Models of Human Liver
Tripathy, S., Chapman, J. D., Han, C. Y., Hogarth, C. A., Arnold, S. L. M., Onken, J. L., Kent, T., Goodlett, D. R., & Isoherranen, N. (2016) · Molecular Pharmacology · doi:10.1124/mol.116.103697 · Cited by 27 · see citing works
“of vitamin A or retinoids and vitamin A deficiency lead to hypertriglyceridemia, elevated total cholesterol and decreased HDL-cholesterol (Bershad et al., 1985; Brelsford and Beute, 2008; Lawrence et al., 2001; Lilley et al., 2013; Staels, 2001).”
BackgroundRetractedSevere generalised rhabdomyolysis with fatal outcome associated with isotretinoin
Hartung, B., Merk, H. F., Huckenbeck, W., Daldrup, T., Neuen-Jacob, E., & Ritz‐Timme, S. (2012) · International Journal of Legal Medicine · doi:10.1007/s00414-012-0750-2 · Cited by 26 · see citing works
“For example isotretinoin is considered to significantly increase plasma levels of cholesterol and low-density-lipoprotein cholesterol [4] and to stimulate tissue plasminogen activator [5].”
Background
- Authors
- Bershad, S., Rubinstein, A., Paterniti, J. R., Le, N.-A., Poliak, S. C., Heller, B., Ginsberg, H. N., Fleischmajer, R., & Brown, W. V.
- Affiliations
- Mount Sinai Health System (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1985-10-17
- Volume
- 313
- Issue
- 16
- Pages
- 981-985
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2338210778
- Cited by
- 217
- References
- 24
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 9 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 6 · 2015: 6 · 2014: 4 · 2013: 9 · 2012: 12
- FWCI
- 12.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › Acne and Rosacea Treatments and Effects
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- isotretinoin, acne, hypertriglyceridemia, plasma lipids, lipoproteins, triglycerides, cholesterol, LDL cholesterol, HDL cholesterol, lipoprotein lipase, hepatic lipase, sex differences, cardiovascular risk, adverse drug reactions
- MeSH terms
- Acne Vulgaris, Adolescent, Adult, Cholesterol, Female, Humans, Lipase, Lipids, Lipoprotein Lipase, Lipoproteins, Cholesterol, HDL, Cholesterol, LDL, Male, Tretinoin, Triglycerides, Isotretinoin
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