Research-Based, Natural Detox Ingredients: Research Findings for Natural Detoxification Support System

by | Mar 5, 2013 | Functional Medicine, Healthy Living

Research Findings for Natural Detoxification Support System: Research-Based, Natural Detox Ingredients

Odom Health & Wellness can prescribe and walk you through a 7-day natural, research-based detox program to support your liver in its natural detoxification pathways.

Overview of Detoxification:

• Few clinical studies have been done in humans on the detoxification process. There is limited research on the selected nutrients and associated detoxification pathways.

• There are two main pathways of detoxification in the liver, known as phase I and phase II. In phase I, non-reactive compounds undergo specific reactions which use oxygen to form a reactive site on the compound. This new intermediary metabolite must then undergo a phase II reaction, which results in the addition of a water soluble group to the reactive site. The end result is a compound that is now able to be excreted in the urine, bile, or stool.1

• The phase I detoxification pathway is mainly composed of the cytochrome P450 family of enzymes.2

• Proper function of both phases is essential for detoxification. Increased phase I activity and or decreased phase II activity has been associated with an increased risk of health related issues.2

• Some nutrients have been found to play supportive roles in the detoxifica tion pathways including: flavonoids, amino acids, glycine, taurine, NAC, and many vitamins and minerals.1

Phase I and Phase II Liver Detox Pathways

Phase I and Phase II Liver Detox Pathways

?N-Acetyl Cysteine:

?• NAC is a sulfhydryl containing (contains sulfur and hydrogen) compound that is commonly used to support liver health. Be cause of this sulfhydryl activity, NAC stimulates glutathione production and is used in one of the 6 phase II detoxification path ways called glutathione conjugation (the attachment of glutathione to the toxin).3

• In vivo studies show that NAC has direct effects on certain mutagenic/carcinogenic toxins that prevents them from converting to more toxic substances.4

• NAC activates a signaling or a messenger protein called nuclear related factor 2 or Nrf2 (NF-E2-Related Factor 2). This protein or transcription factor is encoded by a gene which regulates the expression of a set of antioxidant and detoxifying genes, which protect the body from oxidative stress. NrF2 also up-regulates the expression of glutathione reductase (GR). NAC administration to rats exposed to toxi c phosgene , resulted in elevated expression of Nrf2, which in turn elevated gluta thione metabolism.5

• NAC supplementation resulted in significantly increased levels of SOD, thioredoxin and Nrf2 and circulating levels of glutathi one in tobacco-exposed , myocardial infarcted (MI) rats.6

Glycine:

• One of the 6 phase II detoxification pathways is amino acid conjugation (the attachment of amino acids to the toxin). Glycine is one of the amino acids used in this process. Glycine also aids in glutathione conjugation. 1

• Glycine preserves intracellular glutathione concentration and the protection it offers from oxidative challenge is mediated by a protein called glycine transporter 1 or GLYT1. Glycine treatment of human intestinal Caco-2 and HCT-8 cells against an oxidative agent, reduced the intracellular concentration of reactive oxygen species (ROS), when treated prior to oxidative challenge.7

Taurine:

• One of the 6 phase II detoxification pathways is sulfation (the attachment of sulfur-containing compounds to the toxin). Taurine provides a good source of sulfur.8

• Taurine has direct detoxification properties with specific substances such as endotoxins, carbon tetrachloride, and hypochlo rous acid.8

• Taurine is commonly used to support liver health. Studies show taurine effectively conjugates bile acids and is often used in hepatitis patients.8

• Taurine supplementation in rats , improved the hepatic damages induced by arsenic, by inhibiting protein signalling path ways called PKC?-JNK pathways, which in turn resulted in the restoration of depleted glutathione in the liver.9

Lipoic Acid:

• Lipoic acid is a potent antioxidant. Lipoic acid increases glutathione, vitamin E, and vitamin C levels in the body.10

• In vitro, lipoic acid induced the upregulation of phase II detoxification enzymes including NAD(P)H,quinine oxidoreductase, and glutathione-S-transferase.11

• Lipoic acid has been used to detox mycotoxins (toxic byproducts of fungi and molds). Some mycotoxins have been found to mimic xenobiotics in their destructive effects on the body and in their routes of detoxification.12

• Lipoic acid (LA) activates Phase II detoxification via signalling protein or transcription factor Nrf2. LA treatment increased Nrf2 levels in old rats and also induced Nrf2 binding to a sequence of DNA called antioxidant response element or ARE. Age-related loss of glutathione synthesis , is reversible with lipoic acid.13,14

Green Tea Extract:

• Green tea extract is a potent antioxidant that has phase II stimulating properties. Green tea also contains high levels of benefi cial polyphenols.

• In vivo studies have shown that green tea extract increases phase II enzymes such as glutathione S-transferases, NAD(P) H:quinine reductases, epoxide hydrolases, and UDP-glucuronosyltransferases.15

• Epigallo catechin gallate (EGCG ) is one of the main antioxidant in green tea. EGCG potentiates cellular defense capacity against chemical carcinogens, UV, and oxidative stress via Nrf2-mediated de novo synthesis of antioxidant or phase II detoxi fying enzymes while it can also block metabolic activation of carcinogens. In addition to induction of antioxidant enzymes, Nrf2 has been shown to influence directly or indirectly expression of a battery of genes which are involved in inflammation, cell growth, apoptosis, cell adhesion etc.16

• Carnosol, an antioxidant in Rosemary , induces glutathione-s- transferase , one of the detox enzymes and other important phase II enzymes. Rosemary significantly increased the activities of phase II liver enzymes in mice, to protect the liver and stomach from toxic agents.17

• Rosemarry essential oil and carnosol increased the intracellular GSH levels and GSH synthesis enzyme subunit GCLC/GCLM expression, in HeP G2 cells. Rosemary essential oil and carnosol increased nuclear accumulation of Nrf2 and enhanced Nrf2-antioxidant responsive element (ARE)-reporter activity.18

Rosemary:

• Rosemary contains polyphenols that are potent antioxidants and also have anticarcinogenic properties.19

• Two principle mechanisms have been found in the detoxification actions of rosemary. One, it inhibits the metabolic activation of procarcinogens catalysed by the phase I cytochrome P450 enzymes and two, it induces phase II enzymes.19,1

Ellagic Acid:

• Ellagic acid is a polyphenol found naturally in plants such as grapes, pomegranates and raspberries. • Ellagic acid has been found to induce phase II detoxification enzymes.20,21,22

Vegetable Antioxidant Blend:

• VitaVeggie® is a blend of broccoli powder, broccoli sprout extract, tomato powder, carrot powder, spinach powder, kale powder, brussel sprout powder, and onion extract. It is high in ORAC value and also contains sulphoraphane and glucosinolates.

• In an in vitro study, VitaVeggie® stimulated quinine reductase, the most recognized enzyme belonging to the phase II detoxify ing proteins group.23

• Cruciferous vegetables including broccoli, kale, and brussel sprouts increase the enzyme activity of both phase I and phase II detoxification.24

Sulforaphane has been shown to activate phase II detoxification enzymes in vitro.25

• It is believed that one of the main anticarcinogenic benefits of fruits and vegetables is due to the increase of phase II detoxification enzymes.1,26

• Sulforaphane (SFN), a naturally occurring isothiocyanate derived from cruciferous vegetables, induces phase 2 cytoprotective enzymes, supporting the body’s response to oxidative stress and inflammation. SFN activates Nrf2, one of the signalling proteins or transcription factors, which in turn restores the synthesis of phase II enzymes in cells. SFN also up- regulates the restoration of redox equilibrium.27

Glucosinolates (GLSs) present in Brassica vegetables serve as precursors for biologically active metabolites, which are re leased by myrosinase and induce phase 2 enzymes via the activation of Nrf2.28

Schizandra Berry Extract:

• In animal studies, Schizandra enhances liver detoxification pathways by increasing liver reduced glutathione levels as well as glutathione reductase and glutathione S-transferase activity.29

• Schizandra berry extract increases hepatic glutathione levels and the activities of glucose-6-phosphate and glutathione reductase. Protection from hepatotoxicity and improvements in phase I metabolism are documented in rats administered 1 ml/kg carbon tetrachloride 24 hours after exposure to schisandra extract.30

Fiber/Psyllium Husk:

• Psyllium husk is from the plant Plantago ovata and largely used for its fiber content. Psyllium husk contains a large amount of soluble fiber per volume. Psyllium is used to improve GI transit time, in GI related health issues, and for cardiovascular support.

• Studies show psyllium husk powder upregulates genes involved in bile acid synthesis and binds to bile-acids in the intestines to gently remove them from the body.31,32

Ellagic acid (EA) induces detoxification enzymes NADPH and quinone reductase, which contributes to its chemopreventive properties. Ellagic acid also inhibits certain cytochrome P450 enzymes, to prevent other carcinogens from being metabo lized into more mutagenic forms.33

• EA treatment resulted in a significant rise in total GSH levels and GSH-Px activity in certain brain regions in rat, to protect against sub chronic exposure to dioxin.33

References:

1. Liska, D. J. The detoxification enzyme systems. Altern Med Rev. 1998; 3(3):187-198.

2. Liska, D., Lyon, M. et al. Detoxification and Biotransformational Imbalances. 2005;(22):275-298.

3. Kelly, G. S. Clinical applications of N-acetylcysteine. Altern Med Rev. 1998; 3(2):114-127.

4. De, Flora S., Bennicelli, C. et al. In vivo effects of N-acetylcysteine on glutathione metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds. Carcinogenesis. 1985; 6(12):1735-1745.

5. Ji, L., Liu, R. et al. N-acetylcysteine attenuates phosgene-induced acute lung injury via up-regulation of Nrf2 expression. Inhal Toxicol. 2010; 22(7):535-542.

6. Khanna, A. K., Xu, J. et al. Antioxidant N-acetyl cysteine reverses cigarette smoke-induced myocardial infarction by inhibiting inflammation and oxidative stress in a rat model. Lab Invest. 2011.

7. Howard, A., Tahir, I. et al. Glycine transporter GLYT1 is essential for glycine-mediated protection of human intestinal epithelial cells against oxidative damage. J Physiol. 2010;588(Pt 6):995-1009.

8. Birdsall, T. C. Therapeutic applications of taurine. Altern Med Rev. 1998; 3(2):128-136.

9. Das, J., Ghosh, J. et al. Protective role of taurine against arsenic-induced mitochondria-dependent hepatic apoptosis via the inhibition of PKCdelta-JNK pathway. PLoS One. 2010; 5(9):e12602-

10. Smith, A. R., Shenvi, S. V. et al. Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem. 2004; 11(9):1135-1146.

11. Flier, J., Van Muiswinkel, F. L. et al. The neuroprotective antioxidant alpha-lipoic acid induces detoxication enzymes in cultured astroglial cells. Free Radic Res. 2002; 36(6):695-699.

12. Rogers, S. A. Lipoic acid as a potential first agent for protection from mycotoxins and treatment of mycotoxicosis. Arch Environ Health. 2003; 58(8):528-532.

13. Suh, J. H., Shenvi, S. V. et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc Natl Acad Sci U S A. 2004; 101(10):3381-3386.

14. Shay, K. P., Moreau, R. F. et al. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009; 1790(10):1149-1160.

15. Yu, R., Jiao, J. J. et al. Activation of mitogen-activated protein kinases by green tea polyphenols: potential signaling pathways in the regulation of antioxidant-responsive element-mediated phase II enzyme gene expression. Carcinogenesis. 1997; 18(2):451-456.

16. Na, H. K. and Surh, Y. J. Modulation of Nrf2-mediated antioxidant and detoxifying enzyme induction by the green tea polyphenol EGCG. Food Chem Toxicol. 2008; 46(4):1271-1278.

17. Singletary, K. W. Rosemary extract and carnosol stimulate rat liver glutathione-S-transferase and quinone reductase activities. Cancer. Lett. 1996; 100(1-2):139-144.

18. Chen, C. C., Chen, H. L. et al. Upregulation of NF-E2-related factor-2-dependent glutathione by carnosol provokes a cytoprotective response and enhances cell survival. Acta Pharmacol Sin. 2011; 32(1):62-69.

19. Offord, E. A., Mace, K. et al. Mechanisms involved in the chemoprotective effects of rosemary extract studied in human liver and bronchial cells. Cancer Lett. 1997; 114(1-2):275-281.

20. Barch, D. H., Rundhaugen, L. M. et al. Ellagic acid induces transcription of the rat glutathione S-transferase-Ya gene. Carcinogenesis. 1995; 16(3):665-668.

21. Barch, D. H., Rundhaugen, L. M. et al. Structure-function relationships of the dietary anticarcinogen ellagic acid. Carcinogenesis. 1996; 17(2):265-269.

22. Girish, C. and Pradhan, S. C. Drug development for liver diseases: focus on picroliv, ellagic acid and curcumin. Fundam Clin Pharma col. 2008; 22(6):623-632.

23. VDF FutrueCeuticals R&D Department. VitaVeggie is a potent activator of Quinone Reductase in vitro. 2000;

24. Nestle, M. Broccoli sprouts as inducers of carcinogen-detoxifying enzyme systems: clinical, dietary, and policy implications. Proc Natl Acad Sci U S A. 1997; 94(21):11149-11151.

25. Bacon, J. R., Williamson, G. et al. Sulforaphane and quercetin modulate PhIP-DNA adduct formation in human HepG2 cells and hepatocytes. Carcinogenesis. 2003; 24(12):1903-1911.

26. Talalay, P. and Fahey, J. W. Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism. J Nutr. 2001; 131(11 Suppl):3027S-3033S.

27. Kim, H. J., Barajas, B. et al. Nrf2 activation by sulforaphane restores the age-related decrease of T(H)1 immunity: role of dendritic cells. J Allergy Clin Immunol. 2008; 121(5):1255-1261.

28. Haack, M., Lowinger, M. et al. Breakdown products of neoglucobrassicin inhibit activation of Nrf2 target genes mediated by myrosinase-derived glucoraphanin hydrolysis products. Biol Chem. 2010; 391(11):1281-1293.

29. Ip, S. P., Mak, D. H. et al. Effect of a lignan-enriched extract of Schisandra chinensis on aflatoxin B1 and cadmium chloride-induced hepatotoxicity in rats. Pharmacol Toxicol. 1996; 78(6):413-416.

30. Zhu, M., Yeung, R. Y. et al. Improvement of phase I drug metabolism with Schisandra chinensis against CCl4 hepatotoxicity in a rat model. Planta Med. 2000; 66(6):521-525.

31. Chan, M. Y. and Heng, C. K. Sequential effects of a high-fiber diet with psyllium husks on the expression levels of hepatic genes and plasma lipids. Nutrition. 2008; 24(1):57-66.

32. Burton, R. and Manninen, V. Influence of a psyllium-based fibre preparation on faecal and serum parameters. Acta Med Scand Suppl.1982; 668:91-94.33.

33. Hassoun, E. A., Vodhanel, J. et al. The effects of ellagic acid and vitamin E succinate on antioxidant enzymes activities and glutathione levels in different brain regions of rats after subchronic exposure to TCDD. J Toxicol Environ Health A. 2006; 69(5):381-393.