Liv-A-Tox by Enzymatic Therapy

Introduction:
Throughout all of history, the liver has been recognized for its important role in human health. In ancient Rome, the physician Galen thought that the liver was the principal organ of the human body, arguing that its large, moist nature kept the internal anatomical structures warm. For centuries it was thought that blood was made in the liver due to its extensive vasculature. In 1653, the English physician William Harvey spoke of the liver as a "noble organ" in his Lectures on the Whole of Anatomy.²

For thousands of years it was thought that the liver and human emotions were connected. The word melancholy is from the Greek melankholia, from melas 'black' + khole 'bile', an excess of which was believed to cause feelings of sadness. ² However, to Berber clans living in Morocco, the liver is considered to be the organ of romance and true love. In Berber cultures young persons in love promise their livers, not their hearts to one another, and speak of their “livers melting, being captured, and stolen” when they find true love.³

How Does It Work?:
The human liver is the largest internal organ. About the size of a football, the average adult's liver weighs 3.5 pounds. The entire blood supply passes through the liver many times daily for detoxification and filtration of wastes. Bile, a complex biochemical mixture, is made continuously by the liver to aid in fat digestion. The liver has numerous enzymatic pathways that where drugs, toxins, nutrients, and physiologic byproducts are metabolized and eventually eliminated from the body. ¹ The chart below provides information on each nutrient in Liv-A-Tox.

Ingredient	Functional Category	Benefit to Liver Health
Vitamin A	Bile production	Supports healthy liver cells; promotes immune health within liver tissues, plays role in bile production. ^4-7
Vitamin C	Detoxification	An important antioxidant, especially in liver health.⁸ Recent clinical studies have demonstrated that within cellular structures of the liver vitamin C supports hepatocyte (liver cell) health and supports liver function during detoxification. ^9-11
Niacin	Metabolism	As one of several bile acid sequestrants, niacin is preferred due to its support of healthy triglyceride levels that are already healthy.* ^12-14A recent meta-analysis of niacin that included a long-term outcome study of 2,248 men, found that niacin supports healthy cholesterol production in the liver.*¹⁵
Vitamin B12	Detoxification	Unique among the water soluble vitamins, B12 can be stored in the liver. Healthy vitamin B12 levels are an indication of healthy liver function.*^16-18
Biotin	Metabolism	In addition to being a vital cofactor to several enzymes, biotin is essential in carbohydrate metabolism and the synthesis of fatty acids.¹⁹ Clinical research has demonstrated that biotin supports healthy bile production.^20-21
Choline Bitartrate	Metabolism	Choline is necessary for the transport of lipids.* Clinical research has demonstrated the importance of choline to liver health.* ^22-24
L-Methionine	Metabolism	Provides support for normal fat metabolism.* ^25,26
Barberry (Berberis vulgaris) and Boldo	Bile secretion	Both barberry and boldo help to increase bile flow, support liver health, and encourage overall detoxification.* ^27,28
Fringe Tree (Chionanthus virginicus) Bark	Bile production	The bark of the fringe tree helps increase the production of bile and supports healthy fluid balance and acts as a gentle laxative.* ²⁹
Betaine HCL	Detoxification	Higher intakes of dietary betaine are related to lower homocysteine concentrations independent of other determinants, including folate and other B vitamins. Betaine has been found to protect liver cells from toxins.*^30,31
Choline	Metabolism	Because this vitamin supports fat metabolism in the liver and maintains healthy cholesterol levels in the bloodstream that are already within normal limits, choline may be especially beneficial for people who drink alcohol.*²²
Celandine (Chelidonium majus) Ox Bile Extract Beet (Beta vulgaris) Root Inositol Liver (desiccated) Evening Primrose (Oenothera biennis)	Overall liver support	This proprietary blend of specialized nutrients provides broad support of healthy enzymatic, metabolic, detoxification, filtration, bile production, and bile secretion.*^32-36

References:
1. Guyton AC, Hall JE. Hepatobiliary function. In: Textbook of Medical Physiology.11th Ed. Philadelphia, Pa: W.B. Saunders Company; 2005:673-681.
2. History of the Liver, Spleen, and Gall Bladder. Early Science Lab, Department of the Humanities, Stanford University. Accessed on December 10, 2007. Available at:http://www.stanford.edu/class/history13/earlysciencelab/body/liverpages/livergallbladderspleen.html
3. Courtney-Clark M . Imazighen: The Vanishing Traditions of Berber Women. New York, NY: Clarkson Potter; 1995: 14-15.
4. Takai K, Okuno M, Yasuda I, et al. Prevention of second primary tumors by an acyclic retinoid in patients with hepatocellular carcinoma. Updated analysis of the long-term follow-up data. Intervirology. 2005;48:39-45.
5. Dragnev KH, Petty WJ, Dmitrovsky E. Retinoid targets in cancer therapy and chemoprevention. Cancer Biol Ther. 2003;2:S150-6.
6. Drozda R, Grzegorczyk K, Rutkowski M, Smigielski J, Kolomecki K. [The estimation of antioxidative vitamins concetrations in blood plasma of patients with neoplasms of gallblader and biliary tract] Pol Merkur Lekarski. 2007;131:391-4.
7. Booth LA, Gilmore IT, Bilton RF. Secondary bile acid induced DNA damage in HT29 cells: are free radicals involved? Free Radic Res. 1997;26:135-44.
8. Kojo S. Vitamin C: basic metabolism and its function as an index of oxidative stress. Curr Med Chem. 2004;11:1041-64.
9. Harrison SA, Torgerson S, Hayashi P, Ward J, Schenker S. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol. 2003;98:2485-90.
10. Gueguen S, Pirollet P, Leroy P,et al. Changes in serum retinol, alpha-tocopherol, vitamin C, carotenoids, zinc, and selenium after micronutrient supplementation during alcohol rehabilitation. J Am Coll Nutr. 2003;22:303-10.
11. Vojdani A, Bazargan M, Vojdani E, Wright J. New evidence for antioxidant properties of vitamin C. Cancer Detect Prev. 2000;24:508-23.
12. Sanyal S, Karas RH, Kuvin JT. Present-day uses of niacin: effects on lipid and non-lipid parameters. Expert Opin Pharmacother. 2007;8:1711-7.
13. Mandeville WH, Arbeeny C. Bile acid sequestrants: their use in combination with other lipid-lowering agents. IDrugs. 1999;2:237-42.
14. Bloomgarden ZT. 2nd International Symposium on Triglycerides and HDL: lipid abnormalities and their treatment. Diabetes Care. 2005;28:2795-802.
15. Birjmohun RS, Hutten BA, Kastelein JJ, Stroes ES. Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: a meta-analysis of randomized controlled trials. J Am Coll Cardiol 2005;45:185-97.
16. Halifeoglu I, Gur B, Aydin S, Ozturk A. Plasma trace elements, vitamin B12, folate, and homocysteine levels in cirrhotic patients compared to healthy controls. Biochemistry (Mosc). 2004;69:693-6.
17. Ermens AA, Vlasveld LT, Lindemans J. Significance of elevated cobalamin (vitamin B12) levels in blood. Clin Biochem. 2003;36:585-90.
18. Loew D, Wanitschke R, Schroedter A. Studies on vitamin B12 status in the elderly--prophylactic and therapeutic consequences. Int J Vitam Nutr Res. 1999;69:228-33.
19. Fleming T., ed. Biotin. In: PDR® for Nutritional Supplements. Montvale, NJ: Medical Economics Company; 2001: 27-28.
20. Nagamine T, Saito S, Yamada S, Arai T, Takehara K, Fukui T. Biotinidase activity in patients with liver disease. Scand J Gastroenterol. 1993;28:899-906.
21. Schulpis KH, Gavrili S, Tjamouranis J, Karikas GA, Kapiki A, Costalos C. The effect of neonatal jaundice on biotinidase activity. Early Hum Dev. 2003;72:15-24.
22. Li Z, Vance DE. Phosphatidylcholine and choline homeostasis. J Lipid Res. 2008 Jan 19; [Epub ahead of print]
23. Chawla RK, Wolf DC, Kutner MH, Bonkovsky HL: Choline may be an essential nutrient in malnourished patients with cirrhosis. Gastroenterology 97: 1514–1520, 1989.
24. Savendahl L, Mar MH, Underwood L, Zeisel S: Prolonged fasting results in diminished plasma choline concentration but does not cause liver dysfunction. Am J Clin Nutr 66: 622–625, 1997.
25. Newberne PM, Suphiphat V, Locniskar M, de Camargo JL. Inhibition of hepatocarcinogenesis in mice by dietary methyl donors methionine and choline. Nutr Cancer. 1990;14(3-4):175-81.
26. Kharbanda KK. Role of transmethylation reactions in alcoholic liver disease. World J Gastroenterol. 2007;13:4947-54.
27. Arayne MS, Sultana N, Bahadur SS. The berberis story: Berberis vulgaris in therapeutics. Pak J Pharm Sci. 2007;20:83-92.
28. Monograph. Berberine. Altern Med Rev. 2000;5:175-7.
29. Gülçin I, Elias R, Gepdiremen E, Boyer L, Koksal E. A comparative study on the antioxidant activity of fringe tree (Chionanthus virginicus L.) extracts. Afr J Biotechnol. 2007;6:410-418.
30. Kharbanda KK, Mailliard ME, Baldwin CR, Beckenhauer HC, Sorrell MF, Tuma DJ. Betaine attenuates alcoholic steatosis by restoring phosphatidylcholine generation via the phosphatidylethanolamine methyltransferase pathway. J Hepatol. 2007;46:314-21.
31. Barak AJ, Beckenhauer HC, Tuma DJ. Betaine, ethanol, and the liver: a review. Alcohol. 1996;13:395-8.
32. Biswas SJ, Bhattacharjee N, Khuda-Bukhsh AR. Efficacy of a plant extract (Chelidonium majus L.) in combating induced hepatocarcinogenesis in mice. Food Chem Toxicol. 2007 Dec 15; [Epub ahead of print]
33. Stickel F, Schuppan D. Herbal medicine in the treatment of liver diseases. Dig Liver Dis. 2007;39:293-304.
34. Gaby AR. Natural remedies for scleroderma. Altern Med Rev. 2006;11:188-95.
35. Puri BK. Long-chain polyunsaturated fatty acids and the pathophysiology of myalgic encephalomyelitis (chronic fatigue syndrome). J Clin Pathol. 2007;60:122-4.
36. Doster B. Senior Vice-President Research and Development. Personal communication. February 5, 2007.