Cited by 219Acne and Rosacea Treatments and EffectsLipoproteins and Cardiovascular HealthLipid metabolism and disorders

The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.

Changes in plasma lipids and lipoproteins during isotretinoin therapy for acne.

Bershad, Susan, Rubinstein, Ardon, Paterniti, James R., Le, Ngoc-Anh, Poliak, Susana C., Heller, Bruce, Ginsberg, Henry N., Fleischmajer, Raul, Brown, W. Virgil·1985·New England Journal of Medicine

DOI 10.1056/nejm198510173131604

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1056/nejm198510173131604

Cites

24 of 24 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

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
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
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 3,184
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
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
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
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
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
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
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

Show all 24 references

Research works printed but not linked: 6

Spear, 1983, Mayo Clin Proc, 58, 509
Manual of laboratory operations: lipid research clinics program. Vol. 1. Lipid and lipoprotein analysis. Washington, D.C.: Government Printing Office, 1974. (NIH publication no. 75–628).
The lipid research clinics population studies data book. Vol. 1. The prevalence study. Washington, D.C.: Government Printing Office, 1980. (NIH publication no. 80–1527).
Inter-Society Commission for Heart Disease Resources, 1984, Circulation, 70, 163A
1984, FDA Drug Bull, 14, 15
10.1001/archderm.1983.01650360033009 · DOI

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
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
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
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
Issues in Hyperlipidemic Pancreatitis
Yadav, D. K., & Pitchumoni, C. S. (2003) · Journal of Clinical Gastroenterology · doi:10.1097/00004836-200301000-00016 · Cited by 435
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
Hyperlipidemic Pancreatitis
Toskes, P. P. (1990) · Gastroenterology Clinics of North America · doi:10.1016/s0889-8553(21)00513-6 · Cited by 337
Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2022
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 345
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
“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).”
Background
Quantitative 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
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 218
Secondary causes of hyperlipidemia.
Stone, N. J. (1994) · Medical Clinics of North America · doi:10.1016/s0025-7125(16)30179-1 · Cited by 199
Topical Acne Drugs
Akhavan, A., & Bershad, S. V. (2003) · American Journal of Clinical Dermatology · doi:10.2165/00128071-200304070-00004 · Cited by 185
“[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-citation
A Population-Based Analysis of Laboratory Abnormalities During Isotretinoin Therapy for Acne Vulgaris
Zane, 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
“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.”
Background
Oral 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
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
Modulation 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
Retinoids increase human apo C-III expression at the transcriptional level via the retinoid X receptor. Contribution to the hypertriglyceridemic action of retinoids.
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
“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).”
BackgroundInfluential
Adverse Effects of Retinoids
David, M., Hodak, E., & Lowe, N. J. (1988) · Medical Toxicology · doi:10.1007/bf03259940 · Cited by 135
Retinol, Retinoic Acid, and Retinol-Binding Protein 4 are Differentially Associated with Cardiovascular Disease, Type 2 Diabetes, and Obesity: An Overview of Human Studies
Olsén, T., & Blomhoff, R. (2019) · Advances in Nutrition · doi:10.1093/advances/nmz131 · Cited by 126
“One common side effect of isotretinoin treatment is dyslipidemia (31, 32) as well as elevation of plasma total homocysteine concentration as recently reviewed (33).”
Background
Apoptosis May Explain the Pharmacological Mode of Action and Adverse Effects of Isotretinoin, Including Teratogenicity
Melnik, B. C. (2017) · Acta Dermato Venereologica · doi:10.2340/00015555-2535 · Cited by 131
Drug-Induced Lipid Changes
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 127
“fects[67,72,74] as well as decreases[66,68,69,73] have been reported.”
Background
Laboratory 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
A Comprehensive Update on the Chylomicronemia Syndrome
Goldberg, R. B., & Chait, A. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.593931 · Cited by 125
High Risk for Hyperlipidemia and the Metabolic Syndrome after an Episode of Hypertriglyceridemia during 13-cis Retinoic Acid Therapy for Acne: A Pharmacogenetic Study
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
“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.”
Background
Changes 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
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
Secondary Dyslipidemia
Henkin, Y. (1992) · JAMA · doi:10.1001/jama.1992.03480070077035 · Cited by 99
Recent Advances in Dermatology
Phillips, T. J., & Dover, J. S. (1992) · New England Journal of Medicine · doi:10.1056/nejm199201163260305 · Cited by 95
Isotretinoin therapy for acne vulgaris: a re-evaluation of the need for measurements of plasma lipids and liver function tests
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
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 96
“Medical administration of isotretinoin (13-cis RA) results in hypertriglyceridemia in human subjects with acne [87].”
Background
FoxO1 – 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 92
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
“, 1996) and humans (Lyons et al., 1982; Bershad et al., 1985) often results in increases in serum triglyceride levels.”
Diet Regulation of Long-Chain PUFA Synthesis: Role of Macronutrients, Micronutrients, and Polyphenols on Δ-5/Δ-6 Desaturases and Elongases 2/5
Gonzalez‐Soto, M., & Mutch, D. M. (2020) · Advances in Nutrition · doi:10.1093/advances/nmaa142 · Cited by 88
Retinoic acid represses CYP7A1 expression in human hepatocytes and HepG2 cells by FXR/RXR-dependent and independent mechanisms
Cai, S., He, H., Nguyen, T., Mennone, A., & Boyer, J. L. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m005546 · Cited by 85
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
Idiopathic intracranial hypertension: Can studies of obesity provide the key to understanding pathogenesis?
Ooi, L. Y., Walker, B. R., Bodkin, P. A., & Whittle, I. R. (2008) · British Journal of Neurosurgery · doi:10.1080/02688690701827340 · Cited by 74
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
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
“Hypertriglyceridemia is a metabolic complication of systemic retinoid therapy, which may occur in up to 17% of individuals treated with such therapy (92).”
Background
Side 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
“Nine of 53 patients (17 percent) completing 20 weeks of isotretinoin therapy acquired hypertriglyceridemia, with values of 200 to 600 mg per deciliter [87].”
Background
Isotretinoin and FoxO1
Melnik, B. C. (2011) · Dermato-Endocrinology · doi:10.4161/derm.15331 · Cited by 94
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
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
“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…”
Background
Safety of a new micronized formulation of isotretinoin in patients with severe recalcitrant nodular acne: A randomized trial comparing micronized isotretinoin with standard isotretinoin
Strauss, 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
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
“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).”
BackgroundMethod
Initial 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
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
“A decrease in HDL and an increase in LDL was detected in some patients [81,82] .”
Background
Metabolic syndrome and skin: Psoriasis and beyond
Padhi, T., & Garima (2013) · Indian Journal of Dermatology · doi:10.4103/0019-5154.113950 · Cited by 62
“…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
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
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 92
“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].”
BackgroundInfluential
Safety issues in isotretinoin therapy
Hanson, N., & Leachman, S. A. (2001) · Seminars in Cutaneous Medicine and Surgery · doi:10.1053/sder.2001.28209 · Cited by 60
Effect of long-term beta-carotene and vitamin A on serum cholesterol and triglyceride levels among participants in the Carotene and Retinol Efficacy Trial (CARET)
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
Management of Hypertriglyceridemia
Labossiere, R., & Goldberg, I. J. (2007) · Humana Press eBooks · doi:10.1007/978-1-59745-533-6_10 · Cited by 54
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
The modern age of acne therapy: a review of current treatment options.
Bershad, S. V. (2001) · PubMed · Cited by 54
Self-citation
Retinoids 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
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 52
“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.”
Background
Roles 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 53
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
Overview of Existing Research and Information Linking Isotretinoin (Accutane), Depression, Psychosis, and Suicide
O’Donnell, J. S. (2003) · American Journal of Therapeutics · doi:10.1097/00045391-200303000-00012 · Cited by 51
“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…”
Background
Retinol-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
Phase I Clinical Trial of Alitretinoin and Tamoxifen in Breast Cancer Patients: Toxicity, Pharmacokinetic, and Biomarker Evaluations
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
Retinoids synergized with insulin to induce Srebp-1c expression and activated its promoter via the two liver X receptor binding sites that mediate insulin action
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
Vitamin A status affects obesity development and hepatic expression of key genes for fuel metabolism in Zucker fatty rats
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
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
“Likewise, hypertriglyceridemia is common in patients who receive retinoid treatment for dermatological disorders [11].”
Background
Vitamin paradox in obesity: Deficiency or excess?
Zhou, S. (2015) · World Journal of Diabetes · doi:10.4239/wjd.v6.i10.1158 · Cited by 40
Retinoids and the Skin
Futoryan, T., & Gilchrest, B. A. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1994.tb01461.x · Cited by 41
The Interactions of Insulin and Vitamin A Signaling Systems for the Regulation of Hepatic Glucose and Lipid Metabolism
Chen, G. (2021) · Cells · doi:10.3390/cells10082160 · Cited by 40
“When patients with acne are treated with 13-cis RA (isotretinoin), some of them develop hypertriglyceridemia [72].”
Background
Isotretinoin treatment induces oxidative toxicity in blood of patients with acne vulgaris: a clinical pilot study
Erturan, İ., Nazıroğlu, M., & Akkaya, V. B. (2012) · Cell Biochemistry and Function · doi:10.1002/cbf.2830 · Cited by 40
Retinoids induced Pck1 expression and attenuated insulin-mediated suppression of its expression via activation of retinoic acid receptor in primary rat hepatocytes
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
“When isotretinoin, 13-cis RA, was administered to treat patients with acne, some of them developed isotretinoin-induced hypertriglyceridemia [11].”
Background
Isotretinoin 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
HYPERLIPIDEMIA
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 41
Lipid metabolism and retinoid therapy
Marsden, J. R. (1989) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(89)90074-0 · Cited by 37
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 38
“, 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).”
Background
Effects 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
Retinoic acid receptor agonists regulate expression of ATP-binding cassette transporter G1 in macrophages
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
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
An Observational Study of Isotretinoin Recipients Treated for Acne in a Health Maintenance Organization
McElwee, N. E. (1991) · Archives of Dermatology · doi:10.1001/archderm.1991.01680030061007 · Cited by 34
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 34
Isotretinoin in dermatology
Amichai, B., & Grunwald, M. H. (2000) · Journal of Dermatological Treatment · doi:10.1080/095466300750134214 · Cited by 32
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
Retinoid X receptor agonist elevation of serum triglycerides in rats by potentiation of retinoic acid receptor agonist induction or by action as single agents 2 2Abbreviations: RARs, retinoic acid receptors; and RXRs, retinoid X receptors.
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
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
Isotretinoin and fenofibrate induce adiposity with distinct effect on metabolic profile in a rat model of the insulin resistance syndrome
Šedová, L., Šeda, O., Krenová, D., Křen, V., & Kazdová, L. (2004) · International Journal of Obesity · doi:10.1038/sj.ijo.0802613 · Cited by 30
Opposite in vitro and in vivo regulation of hepatic apolipoprotein A-I gene expression by retinoic acid. Absence of effects on apolipoprotein A-II gene expression.
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
“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…”
Background
Vitamin a supplementation, serum lipids, liver enzymes and C-reactive protein concentrations in obese women of reproductive age
Farhangi, 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 31
Serum levels of albumin, triglycerides, total protein and glucose in rats are altered after oral treatment with low doses of 13‐cis‐retinoic acid or all‐trans‐retinoic acid
Cisneros, F. J., Gough, B., Patton, R. E., & Ferguson, S. A. (2005) · Journal of Applied Toxicology · doi:10.1002/jat.1082 · Cited by 30
“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).”
BackgroundInfluential
Short-term administration of isotretinoin elevates plasma triglyceride concentrations without affecting insulin sensitivity in healthy humans
Stoll, D., Binnert, C., Mooser, V., & Tappy, L. (2003) · Metabolism · doi:10.1016/j.metabol.2003.07.006 · Cited by 30
Drug Reactions
BREATHNACH, S. M. (2010) · Wiley eBooks · doi:10.1002/9781444317633.ch75 · Cited by 31
Retinoic acid regulates several genes in bile acid and lipid metabolism via upregulation of small heterodimer partner in hepatocytes
Mamoon, A. M., Subauste, A. R., Subauste, M. C., & Subauste, J. S. (2014) · Gene · doi:10.1016/j.gene.2014.07.017 · Cited by 30
Variations in lipid and lipoprotein levels during isotretinoin treatment for acne vulgaris with special emphasis on HDL‐cholesterol
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
Retinoids stimulate ApoA-I synthesis by induction of gene transcription in primary hepatocyte cultures from cynomolgus monkey (Macaca fascicularis)
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
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
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 26
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
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
“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-…”
Result
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) · PubMed · Cited by 27
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
“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).”
Background
Retracted
Severe 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
“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)
ORCID: Le, Ngoc-Anh
Ginsberg, Henry N.
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
DOI: 10.1056/nejm198510173131604
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 › Cardiology and Cardiovascular Medicine › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Changes in plasma lipids and lipoproteins during isotretinoin therapy for acne.

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks