Over 70% of Americans take some form of dietary supplement every day, and the supplement industry is currently big business, with a gross of over $28 billion. However, unlike either foods or drugs, supplements do not need to be registered or approved by the US Food and Drug Administration (FDA) prior to production or sales. Under the Dietary Supplement Health and Education Act of 1994, the FDA is restricted to adverse report monitoring postmarketing. Despite widespread consumption, there is limited evidence of health benefits related to nutraceutical or supplement use in well-nourished adults. In contrast, a small number of these products have the potential to produce significant toxicity. In addition, patients often do not disclose supplement use to their physicians. Therefore, the risk of adverse drug-supplement interactions is significant. An overview of the major supplement and nutraceutical classes is presented here, together with known toxic effects and the potential for drug interactions.


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Literature Cited

  1. Mueller C. 1.  1999. The regulatory status of medical foods and dietary supplements in the United States. Nutrition 15:249–51 [Google Scholar]
  2. 2. ODS (Off. Diet. Suppl.). 2011. Dietary Supplements: Background Information Bethesda, MD: Natl. Inst. Health, Off. Diet. Suppl https://ods.od.nih.gov/factsheets/DietarySupplements-HealthProfessional/
  3. Bailey RL, Gahche JJ, Miller PE, Thomas PR, Dwyer JT. 3.  2013. Why US adults use dietary supplements. JAMA Intern. Med. 173:355–61 [Google Scholar]
  4. Moyer MW. 4.  2014. Vitamins of trial. Nature 510:462–64 [Google Scholar]
  5. Funk C. 5.  1912. The etiology of the deficiency diseases. Beri-beri, polyneuritis in birds, epidemic dropsy, scurvy, experimental scurvy in animals, infantile scurvy, ship beri-beri, pellagra. J. State Med. 20:341–68 [Google Scholar]
  6. Woo JJY. 6.  2007. Adverse event monitoring and multivitamin-multimineral dietary supplements. Am. J. Clin. Nutr. 85:323S–24S [Google Scholar]
  7. Velicer CM, Ulrich CM. 7.  2008. Vitamin and mineral supplement use among US adults after cancer diagnosis: a systematic review. J. Clin. Oncol. 26:665–73 [Google Scholar]
  8. Knapik JJ, Steelman RA, Hoedebecke SS, Farina EK, Austin KG, Lieberman HR. 8.  2014. A systematic review and meta-analysis on the prevalence of dietary supplement use by military personnel. BMC Complement. Altern. Med. 14:143 [Google Scholar]
  9. Mulholland CA, Benford DJ. 9.  2007. What is known about the safety of multivitamin-multimineral supplements for the generally healthy population? Theoretical basis for harm. Am. J. Clin. Nutr. 85:318S–22S [Google Scholar]
  10. Guallar E, Stranges S, Mulrow C, Appel LJ, Miller ER III. 10.  2013. Enough is enough: Stop wasting money on vitamin and mineral supplements. Ann. Intern. Med. 159:850–51 [Google Scholar]
  11. Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. 11.  2013. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an updated systematic evidence review for the U.S. Preventive Services Task Force. Ann. Intern. Med. 159:824–34 [Google Scholar]
  12. Ziegler EE, Filer LJ Jr.. 12.  1996. Present Knowledge in Nutrition Washington, DC: Int. Life Sci. Inst. Nutr. Found, 7th ed..
  13. de Kruijk JR, Notermans NC. 13.  2005. Gevoelsstoornissen veroorzaakt door multivitaminepreparaten [Sensory disturbances caused by multivitamin preparations]. Ned. Tijdschr. Geneeskd. 149:2541–44 [Google Scholar]
  14. Bairati I, Meyer F, Gélinas M, Fortin A, Nabid A. 14.  et al. 2005. Randomized trial of antioxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer patients. J. Clin. Oncol. 23:5805–13 [Google Scholar]
  15. Miller ER III, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. 15.  2005. Meta-analysis: High-dosage vitamin E supplementation may increase all-cause mortality. Ann. Int. Med. 142:37–46 [Google Scholar]
  16. Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR. 16.  et al. 1996. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N. Engl. J. Med. 334:1150–55 [Google Scholar]
  17. 17. Alpha-Tocopherol Beta Carotene Cancer Prev. Study Group. 1994. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N. Engl. J. Med. 330:1029–35 [Google Scholar]
  18. Rapola JM, Virtamo J, Ripatti S, Haukka JK, Huttunen JK. 18.  et al. 1998. Effects of α tocopherol and β carotene supplements on symptoms, progression, and prognosis of angina pectoris. Heart 79:454–58 [Google Scholar]
  19. Rapola JM, Virtamo J, Haukka JK, Heinonen OP, Albanes D. 19.  et al. 1996. Effect of vitamin E and beta carotene on the incidence of angina pectoris: a randomized, double-blind, controlled trial. JAMA 275:693–98 [Google Scholar]
  20. Melhus H, Michaëlsson K, Kindmark A, Bergström R, Holmberg L. 20.  et al. 1998. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann. Intern. Med. 129:770–78 [Google Scholar]
  21. Rothman KJ, Moore LL, Singer MR, Nguyen U-SDT, Mannino S, Milunsky A. 21.  1995. Teratogenicity of high vitamin A intake. N. Engl. J. Med. 333:1369–73 [Google Scholar]
  22. Ramanathan VS, Hensley G, French S, Eysselein V, Chung D. 22.  et al. 2010. Hypervitaminosis A inducing intra-hepatic cholestasis—a rare case report. Exp. Mol. Pathol. 88:324–25 [Google Scholar]
  23. Barton JC, Lee PL, West C, Bottomley SS. 23.  2006. Iron overload and prolonged ingestion of iron supplements: clinical features and mutation analysis of hemochromatosis-associated genes in four cases. Am. J. Hematol. 81:760–67 [Google Scholar]
  24. Swanson CA. 24.  2003. Iron intake and regulation: implications for iron deficiency and iron overload. Alcohol 30:99–102 [Google Scholar]
  25. Spector AA, Kim H-Y. 25.  2015. Discovery of essential fatty acids. J. Lipid Res. 56:11–21 [Google Scholar]
  26. Bang HO, Dyerberg J, Nielsen AB. 26.  1971. Plasma lipid and lipoprotein pattern in Greenlandic west-coast Eskimos. Lancet 297:1143–45 [Google Scholar]
  27. Sierra S, Lara-Villoslada F, Olivares M, Jiménez J, Boza J, Xaus J. 27.  2004. La expresión de IL-10 interviene en la regulación de la respuesta inflamatoria por los ácidos grasos omega 3 [Il-10 expression is involved in the regulation of the immune response by omega 3 fatty acids]. Nutr. Hosp. 19:376–82 [Google Scholar]
  28. Leaf A, Kang JX, Xiao Y-F. 28.  2008. Fish oil fatty acids as cardiovascular drugs. Curr. Vasc. Pharmacol. 6:1–12 [Google Scholar]
  29. Gogos CA, Skoutelis A, Kalfarentzos F. 29.  2000. The effects of lipids on the immune response of patients with cancer. J. Nutr. Health Aging 4:172–75 [Google Scholar]
  30. Harris WS, Isley WL. 30.  2001. Clinical trial evidence for the cardioprotective effects of omega-3 fatty acids. Curr. Atheroscler. Rep.174–79
  31. Glück T, Alter P. 31.  2016. Marine omega-3 highly unsaturated fatty acids: from mechanisms to clinical implications in heart failure and arrhythmias. Vascul. Pharmacol. 82:11–19 [Google Scholar]
  32. Gross BW, Gillio M, Rinehart CD, Lynch CA, Rogers FB. 32.  2017. Omega-3 fatty acid supplementation and warfarin: a lethal combination in traumatic brain injury. J. Trauma Nurs. 24:15–18 [Google Scholar]
  33. Buckley MS, Goff AD, Knapp WE. 33.  2004. Fish oil interaction with warfarin. Ann. Pharmacother. 38:50–53 [Google Scholar]
  34. Fang N, Yu S, Badger TM. 34.  2004. Comprehensive phytochemical profile of soy protein isolate. J. Agric. Food Chem. 52:4012–20 [Google Scholar]
  35. Messina M. 35.  2016. Soy and health update: evaluation of the clinical and epidemiologic literature. Nutrients 8:754 [Google Scholar]
  36. Badger TM, Gilchrist JM, Pivik RT, Andres A, Shankar K. 36.  et al. 2009. The health implications of soy infant formula. Am. J. Clin. Nutr. 89:1668S–72S [Google Scholar]
  37. Chen A, Rogan WJ. 37.  2004. Isoflavones in soy infant formula: a review of evidence for endocrine and other activity in infants. Annu. Rev. Nutr. 24:33–54 [Google Scholar]
  38. Harlid S, Adgent M, Jefferson WN, Panduri V, Umbach DM. 38.  et al. 2017. Soy formula and epigenetic modifications: analysis of vaginal epithelial cells from infant girls in the IFED study. Environ. Health Perspect. 125:447–52 [Google Scholar]
  39. Adgent MA, Daniels JL, Rogan WJ, Adair L, Edwards LJ. 39.  et al. 2012. Early-life soy exposure and age at menarche. Paediatr. Perinat. Epidemiol. 26:163–75 [Google Scholar]
  40. Adgent MA, Daniels JL, Edwards LJ, Siega-Riz AM, Rogan WJ. 40.  2011. Early-life soy exposure and gender-role play behavior in children. Environ. Health Perspect. 119:1811–16 [Google Scholar]
  41. Andres A, Moore MB, Linam LE, Casey PH, Cleves MA, Badger TM. 41.  2015. Compared with feeding infants breast milk or cow-milk formula, soy formula feeding does not affect subsequent reproductive organ size at 5 years of age. J. Nutr. 145:871–75 [Google Scholar]
  42. Gilchrist JM, Moore MB, Andres A, Estroff JA, Badger TM. 42.  2010. Ultrasonographic patterns of reproductive organs in infants fed soy formula: comparisons to infants fed breast milk and milk formula. J. Pediatr. 156:215–20 [Google Scholar]
  43. Strom BL, Schinnar R, Ziegler EE, Barnhart KT, Sammel MD. 43.  et al. 2001. Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. JAMA 286:807–14 [Google Scholar]
  44. Hamilton-Reeves JM, Vazquez G, Duval SJ, Phipps WR, Kurzer MS, Messina MJ. 44.  2010. Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis. Fertil. Steril. 94:997–1007 [Google Scholar]
  45. Akingbemi BT, Braden TD, Kemppainen BW, Hancock KD, Sherrill JD. 45.  et al. 2007. Exposure to phytoestrogens in the perinatal period affects androgen secretion by testicular Leydig cells in the adult rat. Endocrinology 148:4475–88 [Google Scholar]
  46. Tan KAL, Walker M, Morris K, Greig I, Mason JI, Sharpe RM. 46.  2006. Infant feeding with soy formula milk: effects on puberty progression, reproductive function and testicular cell numbers in marmoset monkeys in adulthood. Hum. Reprod. 21:896–904 [Google Scholar]
  47. Sharpe RM, Martin B, Morris K, Greig I, McKinnell C. 47.  et al. 2002. Infant feeding with soy formula milk: effects on the testis and on blood testosterone levels in marmoset monkeys during the period of neonatal testicular activity. Hum. Reprod. 17:1692–703 [Google Scholar]
  48. Allred CD, Allred KF, Ju YH, Virant SM, Helferich WG. 48.  2001. Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. Cancer Res 61:5045–50 [Google Scholar]
  49. McCarver G, Bhatia J, Chambers C, Clarke R, Etzel R. 49.  et al. 2011. NTP-CERHR expert panel report on the developmental toxicity of soy infant formula. Birth Defects Res. B Dev. Reprod. Toxicol. 92:421–68 [Google Scholar]
  50. Perry DL, Spedick JM, McCoy TP, Adams MR, Franke AA, Cline JM. 50.  2007. Dietary soy protein containing isoflavonoids does not adversely affect the reproductive tract of male cynomolgus macaques (Macaca fascicularis). J. Nutr. 137:1390–94 [Google Scholar]
  51. Ronis MJ, Gomez-Acevedo H, Blackburn ML, Cleves MA, Singhal R, Badger TM. 51.  2016. Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats. Toxicol. Appl. Pharmacol. 297:68–80 [Google Scholar]
  52. Miousse IR, Sharma N, Blackburn M, Vantrease J, Gomez-Acevedo H. 52.  et al. 2013. Feeding soy protein isolate and treatment with estradiol have different effects on mammary gland morphology and gene expression in weanling male and female rats. Physiol. Genom. 45:1072–83 [Google Scholar]
  53. Zhang J, Lazarenko OP, Wu X, Tong Y, Blackburn ML. 53.  et al. 2012. Differential effects of short term feeding of a soy protein isolate diet and estrogen treatment on bone in the pre-pubertal rat. PLOS ONE 7:e35736 [Google Scholar]
  54. Ronis MJJ, Chen Y, Shankar K, Gomez-Acevedo H, Cleves MA. 54.  et al. 2011. Formula feeding alters hepatic gene expression signature, iron and cholesterol homeostasis in the neonatal pig. Physiol. Genom. 43:1281–93 [Google Scholar]
  55. Singhal R, Shankar K, Badger TM, Ronis MJ. 55.  2009. Hepatic gene expression following consumption of soy protein isolate in female Sprague-Dawley rats differs from that produced by 17β-estradiol treatment. J. Endocrinol. 202:141–52 [Google Scholar]
  56. Ronis M, Hennings L, Gomez-Acevedo H, Badger T. 56.  2014. Different responses to soy and estradiol in the reproductive system of prepubertal male rats and neonatal male pigs. FASEB J 28:373.5 [Google Scholar]
  57. Weaver CM, Alekel DL, Ward WE, Ronis MJ. 57.  2012. Flavonoid intake and bone health. J. Nutr. Gerontol. Geriatr. 31:239–53 [Google Scholar]
  58. Mazzanti G, Menniti-Ippolito F, Moro PA, Cassetti F, Raschetti R. 58.  et al. 2009. Hepatotoxicity from green tea: a review of the literature and two unpublished cases. Eur. J. Clin. Pharmacol. 65:331–41 [Google Scholar]
  59. Mahady G, Parrot J, Lee C, Yun G, Dan A. 59.  2003. Botanical dietary supplement use in peri- and postmenopausal women. Menopause 10:65–72 [Google Scholar]
  60. Lieberman HR, Stavinoha TB, McGraw SM, White A, Hadden LS, Marriott BP. 60.  2010. Use of dietary supplements among active-duty US Army soldiers. Am. J. Clin. Nutr. 92:985–95 [Google Scholar]
  61. Hoyte CO, Albert D, Heard KJ. 61.  2013. The use of energy drinks, dietary supplements, and prescription medications by United States college students to enhance athletic performance. J. Community Health 38:575–80 [Google Scholar]
  62. Navarro VJ, Khan I, Björnsson E, Seeff LB, Serrano J, Hoofnagle JH. 62.  2017. Liver injury from herbal and dietary supplements. Hepatology 65:363–73 [Google Scholar]
  63. Geller AI, Shehab N, Weidle NJ, Lovegrove MC, Wolpert BJ. 63.  et al. 2015. Emergency department visits for adverse events related to dietary supplements. N. Engl. J. Med. 373:1531–40 [Google Scholar]
  64. Brown AC. 64.  2017. An overview of herb and dietary supplement efficacy, safety and government regulations in the United States with suggested improvements. Part 1 of 5 series. Food Chem. Toxicol. 107:449–71 [Google Scholar]
  65. Shekelle PG, Hardy ML, Morton SC, Maglione M, Mojica WA. 65.  et al. 2003. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA 289:1537–45 [Google Scholar]
  66. Haller CA, Benowitz NL. 66.  2000. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N. Engl. J. Med. 343:1833–38 [Google Scholar]
  67. 67. US Natl. Libr. Med. 2016. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury Bethesda, MD: Natl. Inst. Health, US Natl. Libr. Med https://livertox.nlm.nih.gov/index.html
  68. 68. FDA (US Food Drug Adm.). 2004. FDA issues regulation prohibiting sale of dietary supplements containing ephedrine alkaloids and reiterates its advice that consumers stop using these products News Release, Febr. 6. https://wayback.archive-it.org/7993/20170113025516/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108242.htm
  69. Cohen PA. 69.  2012. DMAA as a dietary supplement ingredient. Arch. Intern. Med. 172:1038–39 [Google Scholar]
  70. Shonle HA, Ewald R. 70.  1944. Aminoalkanes US Patent No. 2350318
  71. Eliason MJ, Eichner A, Cancio A, Bestervelt L, Adams BD, Deuster PA. 71.  2012. Case reports: death of active duty soldiers following ingestion of dietary supplements containing 1,3-dimethylamylamine (DMAA). Mil. Med. 177:1455–59 [Google Scholar]
  72. Di Lorenzo C, Moro E, Dos Santos A, Uberti F, Restani P. 72.  2013. Could 1,3 dimethylamylamine (DMAA) in food supplements have a natural origin?. Drug Test. Anal. 5:116–21 [Google Scholar]
  73. 73. World Anti-Doping Agency. 2016. The World Anti-Doping Code: International Standard. Prohibited List January 2017 Montreal: World Anti-Doping Agency https://www.wada-ama.org/sites/default/files/resources/files/2016-09-29_-_wada_prohibited_list_2017_eng_final.pdf
  74. McCarthy CG, Canale RE, Alleman RJ Jr., Reed JP, Bloomer RJ. 74.  2012. Biochemical and anthropometric effects of a weight loss dietary supplement in healthy men and women. Nutr. Metab. Insights 5:13–22 [Google Scholar]
  75. Forrester MB. 75.  2013. Exposures to 1,3-dimethylamylamine-containing products reported to Texas poison centers. Hum. Exp. Toxicol. 32:18–23 [Google Scholar]
  76. Gee P, Tallon C, Long N, Moore G, Boet R, Jackson S. 76.  2012. Use of recreational drug 1,3 dimethylamylamine (DMAA) associated with cerebral hemorrhage. Ann. Emerg. Med. 60:431–34 [Google Scholar]
  77. Gee P, Jackson S, Easton J. 77.  2010. Another bitter pill: a case of toxicity from DMAA party pills. N.Z. Med. J. 123:124–27 [Google Scholar]
  78. Karnatovskaia LV, Leoni JC, Freeman ML. 78.  2015. Cardiac arrest in a 21-year-old man after ingestion of 1,3-DMAA-containing workout supplement. Clin. J. Sport Med. 25:e23–25 [Google Scholar]
  79. Swanson EE, Chen KK. 79.  1946. Comparison of pressor action of aliphatic amines. J. Pharmacol. Exp. Ther. 88:10–13 [Google Scholar]
  80. Bloomer RJ, Harvey IC, Farney TM, Bell ZW, Canale RE. 80.  2011. Effects of 1,3-dimethylamylamine and caffeine alone or in combination on heart rate and blood pressure in healthy men and women. Phys. Sportsmed. 39:111–20 [Google Scholar]
  81. 81. FDA (US Food Drug Adm.). 2012. FDA challenges marketing of DMAA products for lack of safety evidence News Release, Apr. 27. https://wayback.archive-it.org/7993/20170112012624/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm302133.htm
  82. Park SY, Viray M, Johnston D, Taylor E, Chang A. 82.  et al. 2013. Notes from the field: acute hepatitis and liver failure following the use of a dietary supplement intended for weight loss or muscle building—May-October 2013.. Morb. Mortal. Wkly. Rep. 62:817–19 [Google Scholar]
  83. Roytman MM, Pörzgen P, Lee CL, Huddleston L, Kuo TT. 83.  et al. 2014. Outbreak of severe hepatitis linked to weight-loss supplement OxyELITE Pro. Am. J. Gastroenterol. 109:1296–98 [Google Scholar]
  84. Johnston DI, Chang A, Viray M, Chatham-Stephens K, He H. 84.  et al. 2014. Hepatotoxicity associated with the dietary supplement OxyELITE Pro™—Hawaii, 2013.. Drug Test. Anal. 8:319–27 [Google Scholar]
  85. Heidemann LA, Navarro VJ, Ahmad J, Hayashi PH, Stolz A. 85.  et al. 2016. Severe acute hepatocellular injury attributed to OxyELITE Pro: a case series. Dig. Dis. Sci. 61:2741–48 [Google Scholar]
  86. Foley S, Butlin E, Shields W, Lacey B. 86.  2014. Experience with OxyELITE pro and acute liver injury in active duty service members. Dig. Dis. Sci. 59:3117–21 [Google Scholar]
  87. Klontz KC, DeBeck HJ, LeBlanc P, Mogen KM, Wolpert BJ. 87.  et al. 2015. The role of adverse event reporting in the FDA response to a multistate outbreak of liver disease associated with a dietary supplement. Public Health Rep 130:526–32 [Google Scholar]
  88. Chatham-Stephens K, Taylor E, Chang A, Peterson A, Daniel J. 88.  et al. 2017. Hepatotoxicity associated with weight loss or sports dietary supplements, including OxyELITE Pro™—United States, 2013.. Drug Test. Anal. 9:68–74 [Google Scholar]
  89. Narender T, Shweta S, Tiwari P, Papi Reddy K, Khaliq T. 89.  et al. 2007. Antihyperglycemic and antidyslipidemic agent from Aegle marmelos. Bioorg. Med. Chem. Lett. 17:1808–11 [Google Scholar]
  90. 90. FDA (US Food Drug Adm.). 2013. Warning Letter Silver Spring, MD: US Food Drug Adm https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2013/ucm371203.htm
  91. 91. FDA (US Food Drug Adm.). 2013. OxyElite Pro supplements recalled News Release, Nov. 18. http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm374742.htm
  92. Arseculeratne SN, Gunatilaka AAL, Panabokke RG. 92.  1985. Studies on medicinal plants of Sri Lanka. Part 14: toxicity of some traditional medicinal herbs. J. Ethnopharmacol. 13:323–35 [Google Scholar]
  93. 93. US Natl. Libr. Med. 2016. Drug record: OxyELITE Pro. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury Bethesda, MD: Natl. Inst. Health, US Natl. Libr. Med https://livertox.nlm.nih.gov/OxyELITEPro.htm [Google Scholar]
  94. Teschke R, Eickhoff A. 94.  2016. The Honolulu liver disease cluster at the Medical Center: its mysteries and challenges. Int. J. Mol. Sci. 17:476 [Google Scholar]
  95. Tritten TJ. 95.  2015. Pulled twice from exchanges, OxyElite Pro supplement now found to contain Prozac drug. Stars and Stripes Mar. 2. https://www.stripes.com/news/pulled-twice-from-exchanges-oxyelite-pro-supplement-now-found-to-contain-prozac-drug-1.332350
  96. Skalicka-Woźniak K, Georgiev MI, Orhan IE. 96.  2017. Adulteration of herbal sexual enhancers and slimmers: the wish for better sexual well-being and perfect body can be risky. Food Chem. Toxicol. 108:355–67 [Google Scholar]
  97. Geyer H, Parr MK, Koehler K, Mareck U, Schänzer W, Thevis M. 97.  2008. Nutritional supplements cross‐contaminated and faked with doping substances. J. Mass Spectrom. 43:892–902 [Google Scholar]
  98. Bond P, Llewellyn W, Van Mol P. 98.  2016. Anabolic androgenic steroid-induced hepatotoxicity. Med. Hypotheses 93:150–53 [Google Scholar]
  99. Krishnan PV, Feng Z-Z, Gordon SC. 99.  2009. Prolonged intrahepatic cholestasis and renal failure secondary to anabolic androgenic steroid-enriched dietary supplements. J. Clin. Gastroenterol. 43:672–75 [Google Scholar]
  100. Shah NL, Zacharias I, Khettry U, Afdhal N, Gordon FD. 100.  2008. Methasteron-associated cholestatic liver injury: clinicopathologic findings in 5 cases. Clin. Gastroenterol. Hepatol. 6:255–58 [Google Scholar]
  101. Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ. 101.  et al. 2014. Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology 60:1399–408 [Google Scholar]
  102. Bailey RL, Gahche JJ, Lentino CV, Dwyer JT, Engel JS. 102.  et al. 2011. Dietary supplement use in the United States, 2003–2006. J. Nutr. 141:261–66 [Google Scholar]
  103. 103. FDA (US Food Drug Adm.). 2016. Botanical Drug Development: Guidance for Industry Silver Spring, MD: US Food Drug Adm http://www.fda.gov/downloads/Drugs/Guidances/UCM458484.pdf
  104. Wu C-H, Wang C-C, Kennedy J. 104.  2011. Changes in herb and dietary supplement use in the U.S. adult population: a comparison of the 2002 and 2007 National Health Interview Surveys. Clin. Ther. 33:1749–58 [Google Scholar]
  105. Di Lorenzo C, Ceschi A, Kupferschmidt H, Lude S, De Souza Nascimento E. 105.  et al. 2015. Adverse effects of plant food supplements and botanical preparations: a systematic review with critical evaluation of causality. Br. J. Clin. Pharmacol. 79:578–92 [Google Scholar]
  106. Enbom ET, Le MD, Oesterich L, Rutgers J, French SW. 106.  2014. Mechanism of hepatotoxicity due to black cohosh (Cimicifuga racemosa): histological, immunohistochemical and electron microscopy analysis of two liver biopsies with clinical correlation. Exp. Mol. Pathol. 96:279–83 [Google Scholar]
  107. Campos LB, Gilglioni EH, Garcia RF, Brito MdN, Natali MRM. 107.  et al. 2012. Cimicifuga racemosa impairs fatty acid β-oxidation and induces oxidative stress in livers of ovariectomized rats with renovascular hypertension. Free Radic. Biol. Med. 53:680–89 [Google Scholar]
  108. Teschke R. 108.  2010. Kava hepatotoxicity—a clinical review. Ann. Hepatol. 9:251–65 [Google Scholar]
  109. Clouatre DL. 109.  2004. Kava kava: examining new reports of toxicity. Toxicol. Lett. 150:85–96 [Google Scholar]
  110. Hamid S, Rojter S, Vierling J. 110.  1997. Protracted cholestatic hepatitis after the use of prostata. Ann. Intern. Med. 127:169–70 [Google Scholar]
  111. Gabranis I, Koufakis T, Papakrivos I, Batala S. 111.  2015. Echinacea-associated acute cholestatic hepatitis. J. Postgrad. Med. 61:211–12 [Google Scholar]
  112. Kia YH, Alexander S, Dowling D, Standish R. 112.  2016. A case of steroid-responsive valerian-associated hepatitis. Intern. Med. J. 46:118–19 [Google Scholar]
  113. Giampreti A, Lonati D, Locatelli C, Rocchi L, Campailla MT. 113.  2009. Acute neurotoxicity after yohimbine ingestion by a body builder. Clin. Toxicol. 47:827–29 [Google Scholar]
  114. Whittington C. 114.  2007. Exacerbation of hemochromatosis by ingestion of milk thistle. Can. Fam. Physician. 53:1671–73 [Google Scholar]
  115. Martínez-Mir I, Rubio E, Morales-Olivas FJ, Palop-Larrea V. 115.  2004. Transient ischemic attack secondary to hypertensive crisis related to Panax ginseng. Ann. Pharmacother. 38:1970 [Google Scholar]
  116. McKenzie SC, Rahman A. 116.  2010. Bradycardia in a patient taking black cohosh. Med. J. Aust. 193:479–81 [Google Scholar]
  117. Burdette JE, Liu J, Chen S-N, Fabricant DS, Piersen CE. 117.  et al. 2003. Black cohosh acts as a mixed competitive ligand and partial agonist of the serotonin receptor. J. Agric. Food Chem. 51:5661–70 [Google Scholar]
  118. Woodbury A, Sniecinski R. 118.  2016. Garlic-induced surgical bleeding: How much is too much?. A&A Case Rep 7:266–69 [Google Scholar]
  119. Rahman K, Lowe GM, Smith S. 119.  2016. Aged garlic extract inhibits human platelet aggregation by altering intracellular signaling and platelet shape change. J. Nutr. 146:410S–15S [Google Scholar]
  120. Bent S, Goldberg H, Padula A, Avins AL. 120.  2005. Spontaneous bleeding associated with Ginkgo biloba: a case report and systematic review of the literature. J. Gen. Intern. Med. 20:657–61 [Google Scholar]
  121. Tirona RG, Bailey DG. 121.  2006. Herbal product–drug interactions mediated by induction. Br. J. Clin. Pharmacol. 61:677–81 [Google Scholar]
  122. Pang X, Cheng J, Krausz KW, Guo D-A, Gonzalez FJ. 122.  2011. Pregnane X receptor-mediated induction of Cyp3a by black cohosh. Xenobiotica 41:112–23 [Google Scholar]
  123. Chang TKH. 123.  2009. Activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) by herbal medicines. AAPS J 11:590–601 [Google Scholar]
  124. Hermann R, von Richter O. 124.  2012. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med 78:1458–77 [Google Scholar]
  125. 125. Mayo Clinic. 2013. Dosing. Drugs and Supplements: Ginkgo (Ginkgo biloba) Rochester, MN: Mayo Found. Med. Educ. Res. (MFMER) http://www.mayoclinic.org/drugs-supplements/ginkgo/dosing/hrb-20059541 [Google Scholar]
  126. Chen IJ, Liu C-Y, Chiu J-P, Hsu C-H. 126.  2016. Therapeutic effect of high-dose green tea extract on weight reduction: a randomized, double-blind, placebo-controlled clinical trial. Clin. Nutr. 35:592–99 [Google Scholar]
  127. Barry MJ, Meleth S, Lee JY, Kreder KJ, Avins AL. 126.  2011. Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial. JAMA 306:1344–51 [Google Scholar]
  128. 128. Mayo Clinic. 2013. Dosing. Drugs and Supplements: St. John's wort (Hypericum perforatum) Rochester, MN: Mayo Found. Med. Educ. Res. (MFMER) http://www.mayoclinic.org/drugs-supplements/st-johns-wort/dosing/hrb-20060053 [Google Scholar]
  129. 129. Mayo Clinic. 2013. Dosing. Drugs and Supplements: Milk Thistle (Silybum marianum) Rochester, MN: Mayo Found. Med. Educ. Res. (MFMER). http://www.mayoclinic.org/drugs-supplements/milk-thistle/dosing/hrb-20059806 [Google Scholar]
  130. Franco OH, Chowdhury R, Troup J, Voortman T, Kunutsor S. 130.  2016. Use of plant-based therapies and menopausal symptoms: a systematic review and meta-analysis. JAMA 315:2254–63 [Google Scholar]
  131. Gharib M, Samani LN, Panah ZE, Naseri M, Bahrani N, Kiani K. 131.  2015. The effect of valeric on anxiety severity in women undergoing hysterosalpingography. Glob. J. Health Sci. 7:358–63 [Google Scholar]
  132. 132. Drugs.com. 2009. Yohimbe Dallas, TX: Drugs.com https://www.drugs.com/npp/yohimbe.html
  133. Wu X, Li Q, Xin H, Yu A, Zhong M. 133.  2005. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur. J. Clin. Pharmacol. 61:567–72 [Google Scholar]
  134. Gorski JC, Huang SM, Pinto A, Hamman MA, Hilligoss JK. 134.  et al. 2004. The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo. Clin. Pharmacol. Ther. 75:89–100 [Google Scholar]
  135. Whitten DL, Myers SP, Hawrelak JA, Wohlmuth H. 135.  2006. The effect of St John's wort extracts on CYP3A: a systematic review of prospective clinical trials. Br. J. Clin. Pharmacol. 62:512–26 [Google Scholar]
  136. Malati CY, Robertson SM, Hunt JD, Chairez C, Alfaro RM. 136.  et al. 2012. Influence of Panax ginseng on cytochrome P450 (CYP)3A and P-glycoprotein (P-gp) activity in healthy participants. J. Clin. Pharmacol. 52:932–39 [Google Scholar]
  137. Chow HHS, Hakim IA, Vining DR, Crowell JA, Cordova CA. 137.  et al. 2006. Effects of repeated green tea catechin administration on human cytochrome P450 activity. Cancer Epidemiol. Biomark. Prev. 15:2473–76 [Google Scholar]
  138. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB. 138.  et al. 2005. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin. Pharmacol. Ther. 77:415–26 [Google Scholar]
  139. Gurley BJ, Swain A, Hubbard MA, Hartsfield F, Thaden J. 139.  et al. 2008. Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo. Clin. Pharmacol. Ther. 83:61–69 [Google Scholar]
  140. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB. 140.  et al. 2004. In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrusaurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin. Pharmacol. Ther. 76:428–40 [Google Scholar]
  141. Russmann S, Lauterburg BH, Barguil Y, Choblet E, Cabalion P. 141.  et al. 2005. Traditional aqueous kava extracts inhibit cytochrome P450 1A2 in humans: protective effect against environmental carcinogens?. Clin. Pharmacol. Ther. 77:453–54 [Google Scholar]
  142. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB. 142.  et al. 2002. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin. Pharmacol. Ther. 72:276–87 [Google Scholar]
  143. Yin OQP, Tomlinson B, Waye MMY, Chow AHL, Chow MSS. 143.  2004. Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole. Pharmacogenetics 14:841–50 [Google Scholar]
  144. Wang L-S, Zhu B, El-Aty AMA, Zhou G, Li Z. 144.  et al. 2004. The influence of St. John's Wort on CYP2C19 activity with respect to genotype. J. Clin. Pharmacol. 44:577–81 [Google Scholar]
  145. Han Y, Guo D, Chen Y, Chen Y, Tan ZR, Zhou HH. 145.  2009. Effect of silymarin on the pharmacokinetics of losartan and its active metabolite E-3174 in healthy Chinese volunteers. Eur. J. Clin. Pharmacol. 65:585–91 [Google Scholar]
  146. Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. 146.  2012. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur. J. Clin. Pharmacol. 68:213–17 [Google Scholar]
  147. Misaka S, Yatabe J, Müller F, Takano K, Kawabe K. 147.  et al. 2014. Green tea ingestion greatly reduces plasma concentrations of nadolol in healthy subjects. Clin. Pharmacol. Ther. 95:432–38 [Google Scholar]
  148. Hajda J, Rentsch KM, Gubler C, Steinert H, Stieger B, Fattinger K. 148.  2010. Garlic extract induces intestinal P-glycoprotein, but exhibits no effect on intestinal and hepatic CYP3A4 in humans. Eur. J. Pharm. Sci. 41:729–35 [Google Scholar]
  149. Fan L, Tao G-Y, Wang G, Chen Y, Zhang W. 149.  et al. 2009. Effects of Ginkgo biloba extract ingestion on the pharmacokinetics of talinolol in healthy Chinese volunteers. Ann. Pharmacother. 43:944–49 [Google Scholar]
  150. Mueller SC, Uehleke B, Woehling H, Petzsch M, Majcher-Peszynska J. 150.  et al. 2004. Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin. Clin. Pharmacol. Ther. 75:546–57 [Google Scholar]

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