Finding the bad actor: Challenges in identifying toxic constituents in botanical dietary supplements

Food and Chemical Toxicology

Volumn 124, Issue , 2019, Pages 431-438

  Roberts, Georgia K ^a   Gardner, Dale ^b   Foster, Paul M ^a   Howard, Paul C ^c   Lui, Edmund ^d   Walker, Larry ^e   van Breemen, Richard B ^f   Auerbach, Scott S ^a   Rider, Cynthia ^a  

^a NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

^b U S DEPARTMENT OF AGRICULTURE   (United States)

^c NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH   (United States)

^d WESTERN UNIVERSITY   (Canada)

^e UNIVERSITY OF MISSISSIPPI   (United States)

^f OREGON STATE UNIVERSITY   (United States)

Author keywords

Active constituents; Bioassay guided fractionation; Dietary supplement

Indexed keywords

TOXIC SUBSTANCE; PLANT MEDICINAL PRODUCT;

BIOASSAY GUIDED FRACTIONATION; BIOCHEMOMETRIC APPROACH; BOTANICAL DIETARY SUPPLEMENT; CARCINOGENICITY; CHEMOMETRICS; DIETARY SUPPLEMENT; DNA DAMAGE; DRUG IDENTIFICATION; DRUG RECALL; DRUG SAFETY; FRACTIONATION; GENOTOXICITY; HEALTH HAZARD; HUMAN; METABOLOMICS; NONHUMAN; REVIEW; STRUCTURE ACTIVITY RELATION; TOXICOLOGY; ANALYSIS; ANIMAL; BIOASSAY; FOOD CONTAMINATION; PROCEDURES; TOXICITY;

ANIMALS; BIOLOGICAL ASSAY; DIETARY SUPPLEMENTS; FOOD CONTAMINATION; HUMANS; METABOLOMICS; PLANT PREPARATIONS;

EID: 85059052291     PISSN: 02786915     EISSN: 18736351     Source Type: Journal    
DOI: 10.1016/j.fct.2018.12.026     Document Type: Review

References (75)

1. Abourashed, E.A., Khan, I.A., High-performance liquid chromatography determination of hydrastine and berberine in dietary supplements containing goldenseal. J. Pharmacol. Sci. 90 (2001), 817–822.
2. Adike, A., Smith, M.L., Chervenak, A., Vargas, H.E., Hydroxycut-related vanishing bile duct syndrome. Clin. Gastroenterol. Hepatol. 15 (2017), 142–144.
3. Allen, M.R., Kitts, W.D., The effect of yellow pine (Pinus Ponderosa Laws) needles on the reproductivity of the laboratory female mouse. Can. J. Anim. Sci. 41 (1961), 1–8.
4. Araujo, J.L., Worman, H.J., Acute liver injury associated with a newer formulation of the herbal weight loss supplement Hydroxycut. BMJ Case Rep., 2015, 10.1136/bcr-2015-210303 2015.
5. Assinewe, V.A., Amason, J.T., Aubry, A., Mullin, J., Lemaire, I., Extractable polysaccharides of Panax quinquefolius L. (North American ginseng) root stimulate TNFalpha production by alveolar macrophages. Phytomedicine : international journal of phytotherapy and phytopharmacology 9 (2002), 398–404.
6. Avigan, M.I., Mozersky, R.P., Seeff, L.B., Scientific and regulatory perspectives in herbal and dietary supplement associated hepatotoxicity in the United States. Int. J. Mol. Sci., 17, 2016.
7. Avula, B., Wang, Y.H., Isaac, G., Yuk, J., Wrona, M., Yu, K., Khan, I.A., Metabolomics based UPLC-QToF-MS approach for the authentication of various botanicals and dietary supplements. Planta Med., 82, 2016, OA13.
8. Azike, C.G., Charpentier, P.A., Hou, J., Pei, H., King Lui, E.M., The Yin and Yang actions of North American ginseng root in modulating the immune function of macrophages. Chin. Med., 6, 2011, 21.
9. Balachandran, P., Wei, F., Lin, R.C., Khan, I.A., Pasco, D.S., Structure activity relationships of aristolochic acid analogues: toxicity in cultured renal epithelial cells. Kidney Int. 67 (2005), 1797–1805.
10. Baume, N., Mahler, N., Kamber, M., Mangin, P., Saugy, M., Research of stimulants and anabolic steroids in dietary supplements. Scand. J. Med. Sci. Sports 16 (2006), 41–48.
11. Boudreau, M.D., Nondecolorized qualifier is a misnomer for the aloe vera whole leaf extract test. Material. Toxicol Sci, 133, 2013 343-343.
12. Boudreau, M.D., Mellick, P.W., Olson, G.R., Felton, R.P., Thorn, B.T., Beland, F.A., Clear evidence of carcinogenic activity by a whole-leaf extract of aloe barbadensis miller (aloe vera) in F344/N rats. Toxicol. Sci. 131 (2013), 26–39.
13. Boudreau, M.D., Olson, G.R., Tryndyak, V.P., Bryant, M.S., Felton, R.P., Beland, F.A., Aloin, a component of the aloe vera plant leaf, induces pathological changes and modulates the composition of microbiota in the large intestines of F344/N male rats. Toxicol. Sci. 158 (2017), 302–318.
14. Catlin, N.R., Collins, B.J., Auerbach, S.S., Ferguson, S.S., Harnly, J.M., Gennings, C., Waidyanatha, S., Rice, G.E., Smith-Roe, S.L., Witt, K.L., Rider, C.V., How similar is similar enough? A sufficient similarity case study with Ginkgo biloba extract. Food Chem. Toxicol. : an international journal published for the British Industrial Biological Research Association 118 (2018), 328–339.
15. Chen, S., Wan, L.Q., Couch, L., Lin, H.X., Li, Y., Dobrovolsky, V.N., Mei, N., Guo, L., Mechanism study of goldenseal-associated DNA damage. Toxicol. Lett. 221 (2013), 64–72.
16. Ciesla, L., Moaddel, R., Comparison of analytical techniques for the identification of bioactive compounds from natural products. Nat. Prod. Rep. 33 (2016), 1131–1145.
17. Clarke, T.C., Black, L.I., Stussman, B.J., Barnes, P.M., Nahin, R.L., Trends in the use of complementary health approaches among adults: United States, 2002-2012. National Health Statistics Reports 10 (2015), 1–16.
18. Cohen, P.A., Travis, J.C., Venhuis, B.J., A methamphetamine analog (N,alpha-diethyl-phenylethylamine) identified in a mainstream dietary supplement. Drug Test. Anal. 6 (2014), 805–807.
19. Colgate, S.M., Dorling, P.R., Huxtable, C.R., A spectroscopic investigation of swainsonine: an α-mannosidase inhibitor isolated from Swainsona canescens. Aust. J. Chem. 32 (1979), 2257–2264.
20. Cook, D., Gardner, D.R., Pfister, J.A., Panter, K.E., Stegelmeier, B.L., Lee, S.T., Welch, K.D., Green, B.T., Davis, T.Z., Differences in ponderosa pine isocupressic acid concentrations across space and time. Rangelands 32 (2010), 14–17.
21. Dara, L., Hewett, J., Lim, J.K., Hydroxycut hepatotoxicity: a case series and review of liver toxicity from herbal weight loss supplements. World J. Gastroenterol. 14 (2008), 6999–7004.
22. Dickinson, A., Blatman, J., El-Dash, N., Franco, J.C., Consumer usage and reasons for using dietary supplements: report of a series of surveys. J. Am. Coll. Nutr. 33 (2014), 176–182.
23. Dong, T.T., Cui, X.M., Song, Z.H., Zhao, K.J., Ji, Z.N., Lo, C.K., Tsim, K.W., Chemical assessment of roots of Panax notoginseng in China: regional and seasonal variations in its active constituents. J. Agric. Food Chem. 51 (2003), 4617–4623.
24. Dorling, P.R., Huxtable, C.R., Vogel, P., Lysosomal storage in Swainsona spp. toxicosis: an induced mannosidosis. Neuropathol. Appl. Neurobiol. 4 (1978), 285–295.
25. Dunnick, J.K., Singh, B., Nyska, A., Peckham, J., Kissling, G.E., Sanders, J.M., Investigating the potential for toxicity from long-term use of the herbal products, goldenseal and milk thistle. Toxicol. Pathol. 39 (2011), 398–409.
26. EFSA ANS Panel, Safety of hydroxyanthracene derivatives for use in food. EFSA Journal, 16, 2018.
27. Eliason, M.J., Eichner, A., Cancio, A., Bestervelt, L., Adams, B.D., Deuster, P.A., Case reports: death of active duty soldiers following ingestion of dietary supplements containing 1,3-dimethylamylamine (DMAA). Mil. Med. 177 (2012), 1455–1459.
28. Everist, S.L., Posionous Plants of Australia. 1981, Angus and Robertson, London.
29. Findeis, M.A., Schroeder, F., McKee, T.D., Yager, D., Fraering, P.C., Creaser, S.P., Austin, W.F., Clardy, J., Wang, R., Selkoe, D., Eckman, C.B., Discovery of a novel pharmacological and structural class of gamma secretase modulators derived from the extract of actaea racemosa. ACS Chem. Neurosci. 3 (2012), 941–951.
30. Fong, T.L., Klontz, K.C., Canas-Coto, A., Casper, S.J., Durazo, F.A., Davern, T.J. 2nd, Hayashi, P., Lee, W.M., Seeff, L.B., Hepatotoxicity due to hydroxycut: a case series. Am. J. Gastroenterol. 105 (2010), 1561–1566.
31. Gardner, D.R., Molyneux, R.J., James, L.F., Panter, K.E., Stegelmeier, B.L., Ponderosa pine needle-induced abortion in beef cattle: identification of isocupressic acid as the principle active compound. J. Agric. Food Chem. 42 (1994), 756–761.
32. Geyer, H., Parr, M.K., Koehler, K., Mareck, U., Schanzer, W., Thevis, M., Nutritional supplements cross-contaminated and faked with doping substances. J. Mass Spectrom. : JMS 43 (2008), 892–902.
33. Gluck, J., Buhrke, T., Frenzel, F., Braeuning, A., Lampen, A., In silico genotoxicity and carcinogenicity prediction for food-relevant secondary plant metabolites. Food Chem. Toxicol. 116 (2018), 298–306.
34. Hubert, J., Nuzillard, J.M., Renault, J.H., Dereplication strategies in natural product research: how many tools and methodologies behind the same concept?. Phytochemistry Rev. 16 (2017), 55–95.
35. James, L.F., Panter, K.E., Steglemeier, B.L., Ralphs, M.H., Pfister, J.A., Gardner, D.R., Astragalus and Oxytropis posion livestock with different toxins. Sterling, T.M., Thompson, D.C., (eds.) Locoweed Research, 1999, New Mexico State University, Las Cruces, NM.
36. Kellogg, J.J., Todd, D.A., Egan, J.M., Raja, H.A., Oberlies, N.H., Kvalheim, O.M., Cech, N.B., Biochemometrics for natural products research: comparison of data analysis approaches and application to identification of bioactive compounds. J. Nat. Prod. 79 (2016), 376–386.
37. Klontz, K.C., DeBeck, H.J., LeBlanc, P., Mogen, K.M., Wolpert, B.J., Sabo, J.L., Salter, M., Seelman, S.L., Lance, S.E., Monahan, C., Steigman, D.S., Gensheimer, K., The role of adverse event reporting in the FDA response to a multistate outbreak of liver disease associated with a dietary supplement. Publ. Health Rep. 130 (2015), 526–532.
38. Lim, W., Mudge, K.W., Vermeylen, F., Effects of population, age, and cultivation methods on ginsenoside content of wild American ginseng (Panax quinquefolium). J. Agric. Food Chem. 53 (2005), 8498–8505.
39. Lobb, A., Hepatoxicity associated with weight-loss supplements: a case for better post-marketing surveillance. World J. Gastroenterol. 15 (2009), 1786–1787.
40. Low, T.Y., Wong, K.O., Yap, A.L.L., De Haan, L.H.J., Rietjens, I.M.C.M., The regulatory framework across international jurisdictions for risks associated with consumption of botanical food supplements. Compr Rev Food Sci F 16 (2017), 821–834.
41. Lui, E.M.K., Azike, C.G., Guerrero-Analco, J.A., Romeh, A.A., Pei, H., Kaldas, S.J., Arnason, J.T., Charpentier, P.A., Bioactive polysaccharides of American ginseng panax quinquefolius L. In modulation of immune function: phytochemical and pharmacological characterization. Karunaratne, D.N., (eds.) The Complex World of Polysaccharides, 2012, IntechOpen.
42. Lunsford, K.E., Bodzin, A.S., Reino, D.C., Wang, H.L., Busuttil, R.W., Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation. World J. Gastroenterol. 22 (2016), 10071–10076.
43. Ma, J., Pawar, R., Grundel, E., Validation of an LC-MS/MS method for analysis of anti-diabetic, anti-obesity, and cholesterol-lowering drugs in botanical dietary supplements labelled for blood sugar management. Abstr. Pap. Am. Chem. Soc., 254, 2017.
44. Maan, A.A., Nazir, A., Khan, M.K.I., Ahmad, T., Zia, R., Murid, M., Abrar, M., The therapeutic properties and applications of Aloe vera: a review. J. Herb. Med. 12 (2018), 1–10.
45. Madhu, S.K., Shaukath, A.K., Vijayan, V.A., Efficacy of bioactive compounds from Curcuma aromatica against mosquito larvae. Acta Trop. 113 (2010), 7–11.
46. Mathews, F.R., Locoism in Domestic Animals, Texas Agricultural Experiment Station Bulletin. 1932.
47. McKinney, J.D., Richard, A., Waller, C., Newman, M.C., Gerberick, F., The practice of structure activity relationships (SAR) in toxicology. Toxicol. Sci. 56 (2000), 8–17.
48. Miousse, I.R., Skinner, C.M., Lin, H.X., Ewing, L.E., Kosanke, S.D., Williams, D.K., Avula, B., Khan, I.A., ElSohly, M.A., Gurley, B.J., Koturbash, I., Safety assessment of the dietary supplement OxyELITE (TM) Pro (New Formula) in inbred and outbred mouse strains. Food Chem. Toxicol. 109 (2017), 194–209.
49. Nikolic, D., Godecke, T., Chen, S.N., White, J., Lankin, D.C., Pauli, G.F., van Breemen, R.B., Mass spectrometric dereplication of nitrogen-containing constituents of black cohosh (Cimicifuga racemosa L.). Fitoterapia 83 (2012), 441–460.
50. NTP, Toxicology and carcinogenesis studies of Goldenseal root powder (Hydrastis Canadensis) in F344/N rats and B6C3F1/N mice (feed studies). NTP, (eds.) Technical Report Series, 2010, NIEHS/NTP, Research Triangle Park, NC.
51. NTP, Toxicology and carcinogenesis studies of Ginseng (CAS NO. 50647-08-0) in F344/N rats and B6C3F1/N mice (gavage studies). NTP, (eds.) Technical Report Series, 2011, NIEHS/NTP, Research Triangle Park, NC.
52. NTP, Toxicology and carcinogenesis studies of Kava Kava extract (CAS NO. 9000-38-8) in F344/N rats and B6C3F1/N mice (gavage studies). NTP, (eds.) Technical Report Series, 2012, NIEHS/NTP, Research Triangle Park, NC.
53. NTP, Toxicology and carcinogenesis studies of Ginkgo biloba extract (CAS No. 90045-36-6) in F344/N rats and B6C3F1/N mice (gavage studies). NTP, (eds.) Technical Report Series, 2013, NIEHS/NTP, Research Triangle Park, NC.
54. NTP, Toxicology studies of green tea extract in F344/NTac rats and B6C3F1/N mice and toxicology and carcinogenesis studies of green tea extract in Wistar Han [Crl:WI(Han)] rats and B6C3F1/N mice (gavage studies). NTP, (eds.) Technical Report Series, 2016, NIEHS/NTP, Research Triangle Park, NC.
55. Olivon, F., Allard, P.M., Koval, A., Righi, D., Genta-Jouve, G., Neyts, J., Apel, C., Pannecouque, C., Nothias, L.F., Cachet, X., Marcourt, L., Roussi, F., Katanaev, V.L., Touboul, D., Wolfender, J.L., Litaudon, M., Bioactive natural products prioritization using massive multi-informational molecular networks. ACS Chem. Biol. 12 (2017), 2644–2651.
56. Overk, C.R., Yao, P., Chadwick, L.R., Nikolic, D., Sun, Y.K., Cuendet, M.A., Deng, Y.F., Hedayat, A.S., Pauli, G.F., Farnsworth, N.R., van Breemen, R.B., Bolton, J.L., Comparison of the in vitro estrogenic activities of compounds from hops (Humulus lupulus) and red clover (Trifolium pratense). J. Agric. Food Chem. 53 (2005), 6246–6253.
57. Powell, S.L., Goedecke, T., Nikolic, D., Chen, S.N., Ahn, S., Dietz, B., Farnsworth, N.R., van Breemen, R.B., Lankin, D.C., Pauli, G.F., Bolton, J.L., In vitro serotonergic activity of black cohosh and identification of N-omega-Methylserotonin as a potential active constituent. J. Agric. Food Chem. 56 (2008), 11718–11726.
58. Prince, E.K., Pohnert, G., Searching for signals in the noise: metabolomics in chemical ecology. Anal. Bioanal. Chem. 396 (2010), 193–197.
59. Qiu, F., Cai, G.P., Jaki, B.U., Lankin, D.C., Franzblau, S.G., Pauli, G.F., Quantitative purity-activity relationships of natural products: the case of anti-tuberculosis active triterpenes from oplopanax horridus. J. Nat. Prod. 76 (2013), 413–419.
60. Ralphs, M.H., Manners, G.D., Pfister, J.A., Gardner, D.R., James, L.F., Toxic alkaloid concentration in tall larkspur species in the western US. J. Range Manag. 50 (1997), 497–502.
61. Sasidharan, S., Chen, Y., Saravanan, D., Sundram, K.M., Latha, L.Y., Extraction, isolation and characterization of bioactive compounds from plants’ extracts. Afr J Tradit Complem 8 (2011), 1–10.
62. Schlag, E.M., McIntosh, M.S., Ginsenoside content and variation among and within American ginseng (Panax quinquefolius L.) populations. Phytochemistry 67 (2006), 1510–1519.
63. Shao, A., Broadmeadow, A., Goddard, G., Bejar, E., Frankos, V., Safety of purified decolorized (low anthraquinone) whole leaf Aloe vera (L) Burm. f. juice in a 3-month drinking water toxicity study in F344 rats. Food Chem. Toxicol. 57 (2013), 21–31.
64. Sharma, S.B., Gupta, R., Drug development from natural resource: a systematic approach. Mini Rev. Med. Chem. 15 (2015), 52–57.
65. Shipkowski, K.A., Betz, J.M., Birnbaum, L.S., Bucher, J.R., Coates, P.M., Hopp, D.C., MacKay, D., Oketch-Rabah, H., Walker, N.J., Welch, C., Rider, C.V., Naturally complex: perspectives and challenges associated with botanical dietary supplement safety assessment. Food Chem. Toxicol. : an international journal published for the British Industrial Biological Research Association 118 (2018), 963–971.
66. Singh, S., Prasad, B., Savaliya, A.A., Shah, R.P., Strategies for characterizing sildenafil, vardenafil, tadalafil and their analogues in herbal dietary supplements, and detecting counterfeit products containing these drugs. Trends Anal. Chem. 28 (2009), 13–28.
67. Somerville, S.J., Lewis, M., Kuipers, H., Accidental breaches of the doping regulations in sport: is there a need to improve the education of sportspeople?. Br. J. Sports Med. 39 (2005), 512–516 discussion 516.
68. Soni, M.G., Carabin, I.G., Griffiths, J.C., Burdock, G.A., Safety of ephedra: lessons learned. Toxicol. Lett. 150 (2004), 97–110.
69. Stickel, F., Shouval, D., Hepatotoxicity of herbal and dietary supplements: an update. Arch. Toxicol. 89 (2015), 851–865.
70. UNEP, Programme, U.N.E., (eds.) UNEP Frontiers: 2016 Report: Emerging Issues of Environmental Concern, 2016, UNEP Division of Early Warning and Assessment, Nairobi, Kenya.
71. Waidyanatha, S., Ryan, K., Roe, A.L., Jia, W., Paine, M.F., Ferguson, S., Gurley, B.J., Welch, K., Chow, M.S.S., Devito, M., Rider, C., Follow that botanical: challenges and recommendations for assessing absorption, distribution, metabolism and excretion of botanical dietary supplements. Food Chem. Toxicol. : an international journal published for the British Industrial Biological Research Association(121), 2018, 194–202.
72. Weller, M.G., A unifying review of bioassay-guided fractionation, effect-directed analysis and related techniques. Sensors 12 (2012), 9181–9209.
73. Westenburg, H.E., Lee, K.J., Lee, S.K., Fong, H.H., van Breemen, R.B., Pezzuto, J.M., Kinghorn, A.D., Activity-guided isolation of antioxidative constituents of Cotinus coggygria. J. Nat. Prod. 63 (2000), 1696–1698.
74. Wiklund, S., Johansson, E., Sjostrom, L., Mellerowicz, E.J., Edlund, U., Shockcor, J.P., Gottfries, J., Moritz, T., Trygg, J., Visualization of GC/TOF-MS-based metabolomics data for identification of biochemically interesting compounds using OPLS class models. Anal. Chem. 80 (2008), 115–122.
75. Wu, C.H., Wang, C.C., Kennedy, J., 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. Therapeut. 33 (2011), 1749–1758.