• Liver-HealthVitamins,Nutrients&Herbs*

• SupportsLiverDetoxification, ProtectionandRegeneration*

• 250mgof30:1MilkThistle ExtractPerServing

• ActivatesAlcohol MetabolizingEnzymes*

Supplement FactsServing Size 3 Tablets Servings Per Container 30

Amount Per Serving % DVVitamin B1 (as thiamine mononitrate) 15 mg 1000%Vitamin B6 (as pyridoxine HCl) 10 mg 500%Folic Acid 400 mcg 100%Biotin 100 mcg 33%Pantethine (coenzyme vitamin B5) 300 mg *Chromium (from Saccharomyces cerevisiae) 100 mcg 83%

Artichoke Leaf Extract (Cynara scolymus) 600 mg *Milk Thistle Seed 30:1 Extract 250 mg * (Silybum marianum) (80% total flavonoids)NAC (N-acetyl-L-cysteine) 250 mg *Alpha Lipoic Acid 100 mg *PicroMax® (Picrorhiza kurroa) (4% kutkin) (root) 100 mg *Uridine 5’-Monophosphate 50 mg *Sulforaphane Glucosinolate 5 mg * (from BroccoMax®, Brassica oleracea Italics) (seed extract)

* Daily Value not established.

OptimizerLiver

™

What Does Liver Optimizer™ Do? Liver Optimizer™ combines herbs and other nutrients known to impact detoxification and overall liver function.* It is especially directed toward Phase 2 enzymes, which assist in the processing and removal of toxins from the body.* Artichoke and milk thistle extracts have been shown to affect bile action and glutathione levels. The sulfur-containing compounds, alpha lipoic acid and N-acetylcysteine (NAC), are also involved in the regulation of glutathione. Additionally, NAC conjugates acetaldehyde, a problematic intermediate of alcohol metabolism. PicroMax® is a proprietary, standardized extract of Picrorhiza kurroa, an herb well-regarded in Ayurveda. Sulforaphane glucosinolate, from BroccoMax®, is a precursor to sulforaphane, an inducer of Phase 2 detoxifying enzymes. B complex vitamins are indispensable components of enzymes in the liver.

In her 1962 groundbreaking book, Silent Spring, Rachel Carson wrote: “For the first time in the history of the world every human being

is now subjected to contact with dangerous chemicals, from the moment of conception until death.” Of course humans have always been exposed to potentially harmful chemicals from plants and other sources, but Rachel Carson’s point is well taken. Modern living exposes

all of us to an unprecedented number of chemicals on a daily basis. This

includes environmental toxins such as heavy metals, pesticides, industrial compounds and chemical byproducts, medications, cosmetic additives, inorganic chemicals, etc. These chemical substances which are foreign to the biological system are referred to as “xenobiotics.”

The good news is that the body was designed to detoxify and excrete

xenobiotics. The bad news is our bodies may not always be equipped to handle the volume of modern, environmental pollutants and toxic substances. This problem may be exacerbated by the fact that the refining of many of our foodstuffs has caused them to provide considerably less of the nutrients that are essential to the detoxification process.

Suggested UsageTake 3 tablets per day, preferably one with each meal or as directed by your qualified healthcare professional. NOTE: If you have a medical condition (especially diabetes or being treated for glucose control), are pregnant, lactating, trying to conceive, under the age of 18, or taking medications (especially for glucose control), consult your healthcare professional before using this product.

Other Ingredients: Cellulose, calcium phosphate, stearic acid (vegetable source), maltodextrin, magnesium stearate (vegetable source), silicon dioxide and a food grade coating.

Contains: Soy (in trace amounts).

N o w h e a t , n o g l u t e n , n o d a i r y, n o e g g , no f ish/shel l f ish, no peanuts/tree nuts.

DETOX

Ramifications of Toxic OverloadThe ramifications of toxic overload can vary from one individual to another. One possible ramification is multiple chemical sensitivities (MCS). MCS is a condition in which a person experiences various symptoms in response to being exposed to certain types of chemicals, primarily (but not limited to) those of petroleum and coal-tar derivation. The possible symptoms are many and may include headaches, fatigue, mood fluctuation and an overall feeling of malaise. MCS seems to develop after consistent, long-term exposure to certain chemicals at home or in the workplace. Eventually, the person develops intolerance to these chemicals, and starts suffering from MCS. For many MCS people, a

sensitivity reaction will occur when exposed to even minute amounts of the offending chemicals which, in turn, can lead to severe symptoms characteristic of the MCS condition.

Of course an individual may suffer from toxic overload without having full-blown MCS. In fact, the most common symptom of toxic overload is probably fatigue. Other common symptoms include headache, muscle and joint pain, irritability, mood fluctuations, mental confusion, gastrointestinal and/or cardiovascular irregularities, flu-like symptoms (without having the flu) or allergic reactions including hives, stuffy or runny nose, sneezing & coughing.2

How to Deal With Toxic OverloadThe question of how to deal with toxic overload has a multipart answer which includes adapting to a healthier diet and reducing exposure to xenobiot ics. The books Mult ip le Chemical Sensitivity by Gibson (2000, New Harbinger Publications, Inc.) and Staying Well in a Toxic

World by Lawson (1993, The Nobel Press) provide good direction on how to do this. Another part to the answer is to help your liver to become more proficient at detoxification. That’s what this article is really about. So now let’s have a brief overview on how the liver goes about detoxification.

Artichoke Artichoke’s therapeutic benefit in detoxification is centered on its choleretic effects, or ability to stimulate bile flow, which has been demonstrated in several studies.11 Several constituents are reported to have antioxidant activity.12 Preliminary research suggests that artichoke leaf extract might also protect liver cells from damage.13,12,11,14 A mixture of polyphenols and flavonoids might contribute to hepatoprotective activity.11,14 In cultured liver cells, artichoke extract not only provided antioxidant protection from a toxic chemically-induced insult, but also showed diminished loss of cellular glutathione reserves.6

N-acetylcysteine N-acetylcysteine (NAC) is the precursor to glutathione.25 It stimulates glutathione synthesis and promotes liver detoxification; as well as acting as a powerful scavenger of free radicals.26 ,27

Historically the most prevalent and well-accepted use of NAC has been as an antidote for acetaminophen (Tylenol®, paracetamol) poisoning.25 The resultant liver toxicity is due to an acetaminophen metabolite that depletes the liver cells of glutathione and causes liver cell damage and possibly even death. NAC has also been effective for heavy metal poisoning by gold, silver, copper, mercury, lead, and arsenic, as well as in cases of poisoning by carbon tetrachloride, acrylonitriles, halothane, paraquat, acetaldehyde, coumarin, and interferon.28 Since detoxification of mercury depletes glutathione, the use of NAC doubly makes sense.

Detoxification By the LiverWater soluble toxins can pass through our bodies unchanged and be eliminated in the stool, sweat or urine. Fat soluble toxins, however, cannot be excreted without undergoing metabolic transformation (detoxification) in the liver so that they can become water soluble. Liver cells have sophisticated mechanisms to break down toxic substances. These include both endogenous (produced by the body) and exogenous (obtained from the environment; i.e., xenobiotics) substances. Every drug, chemical, pesticide and hormone, is broken down or metabolized via detoxification pathways in the liver called “phase 1” and “phase 2.” 4,5,6

Phase 1Phase 1 utilizes cytochrome P450 enzymes produced in the liver. These enzymes initiate reactions that generally involve exposing or adding a “functional group” to the toxic molecule. This process of making the molecule more reactive is required as the first step in increasing its water solubility for excretion. Some chemicals are already highly reactive and they have functional groups, so they can bypass phase 1 and go right to phase 2. The majority, however, first need phase 1 activation. Unfortunately, phase 1 does generate free radicals which mean that there is greater potential for oxidative damage at this time.7,5

Phase 2Phase 2 involves the coupling (attaching) or conjugation of a water soluble substance which is endogenously produced or sourced by the body, to the toxin. This makes the toxic molecule more water soluble and therefore less toxic. If the molecule is large, it is then excreted via the bile. Otherwise, it is excreted in the urine.7,5 Now that we’ve briefly examined the process of liver detoxification, let’s take a look at the nutraceuticals found in Liver PF® that can be used to support and promote liver detoxification.

Vitamin B6 & Folic AcidHomocysteine is a peptide that plays a negative role in the development of cardiovascular disease. It also has other adverse roles, including participating in some capacity in suboptimal liver function.8 Certain nutrients help to promote healthy levels of homocysteine within a normal range.This includes vitamin B6 and folic acid.9,10

Milk ThistleIn herbal medicine, Milk Thistle (Silybum marianum) is arguably the premium liver herb. The active component in Milk Thistle is its flavonoids collectively called silymarin; and the majority of Milk Thistle-related research has been conducted on this component. Silymarin has long been recognized for its ability to benefit people with suboptimal liver function. 15,16,17,18,19

Some toxic molecules pass through the glutathione conjugation pathway. A deficiency of this conjugating amino peptide can reduce the clearance of solvents from the bloodstream. Research shows that silymarin protects against glutathione depletion20, and increases liver glutathione status.21 Since glutathione is one of the primary conjugating agents in phase 2, this is a significant contribution by Milk Thistle in supporting detoxification by the liver. 22

In addition, Milk Thistle also provides liver protection by stabilizing liver cell membranes. It alters the structure of the outer cell membrane in such a way as to prevent the penetration of the liver by toxins into interior of the cell. Milk Thistle also increases the regenerative ability of the liver and the formation of new liver cells. Further studies concluded that other actions of silymarin include preventing the recirculation of toxins and

regeneration of damaged liver cells. Other studies

indicate that Milk T h i s t l e m a y prevent l iver damage from liver poisoning prescription

medications.23,24

Pantethine & Uridine Pantethine activates alcohol metabolizing enzymes and is a co-factor in carbohydrate and lipid metabolism. Uridine is important in the biosynthesis of DNA and in the preservation and transfer of genetic information.

Alpha-Lipoic AcidAlpha-lipoic acid is a natural antioxidant that can scavenge free radicals both intra- and extra-cellularly.29 It is both water and fat soluble and can regenerate antioxidants, such as vitamin E, vitamin C, and glutathione, and prevent oxidative damage.29,30,31,32 The antioxidant effects of alpha-lipoic acid might be beneficial in suboptimal liver function in which oxidative stress is a factor. Alpha-lipoic acid has shown promise in preventing certain types of toxic damage, including damage from heavy metals (lead, arsenic, cadmium, mercury) and chemicals (hexachlorobenzene, n-hexane).29,33,34,35,36

Picrorrhiza kurroaIn research, Picrorrhiza kurroa, an Ayurvedic herb exhibited a dose-dependent choleretic effect, increasing bile flow, bile salt and bile acid output.37 Picrorrhiza has been shown to protect liver cells from a wide variety of insults including toxicity from Amanita, carbon tetrachloride, galactosamine, ethanol, aflatoxin B1, acetaminophen, thioacetamide, oxytetracyline, and monocrotaline. When compared with silymarin, the hepatoprotective effect was found to be similar, or in many cases, superior to the effect of silymarin.38

Sulforaphane GlucosinolateSulforaphane glucosinolate is a water-soluble chemical compounds found in cruciferous vegetables. This compound has been shown to induce specific phase I enzymes. Gut flora have been shown to convert the glucosinolate into phenylethylisothiocyanate (PEITC). PEITC has been shown to inhibit chemically-induced mutagenic cells in the lung and colon, and promote excretion of mutagens. The proposed mechanism for these activities include inhibition of select phase I enzymes with concomitant induction of several phase II enzymes, including glucuronosyltransferases and glutathione-S-transferases.6

References

1. Rogers SA. Chemical Sensitivity: Breaking the Paralyzing Paradigm. Internal Medicine World Report 1992; February 1-14:15-16.

2. Lawson L. Staying Well in a Toxic World. Chicago: The Nobel Press, Inc.; 1993.

3. Gibson PR. Multiple Chemical Sensitivity. Oakland, California: New Harbinger Publications, Inc.; 2000.

4. Murray Rk, Granner DK, Mayes PA, Rodwell VW. Harper’s Biochemistry, 25th ed. New York: McGraw Hill; 200:780-786.

5. Lüllmann H. Mohr K, Ziegler A, Bieger D. Color Atlas of Pharmacology, 2nd ed. Stuttgart: Thieme; 2000:32-39.

6. Roundtree R. The Use of Phytochemicals in the Biotransformation and Elimination of Environmental Toxins. IN Medicines from the Earth 2003: Official Proceedings. Brevard, North Carolina: Gaia Herbal Research Institute; 2003:115-128.

7. Murray Rk, Granner DK, Mayes PA, Rodwell VW. Harper’s Biochemistry, 25th ed. New York: McGraw Hill; 200:780-786.

8. Ferré N, Gómez F, Camps J. Plasma Homocysteine Concentrations in Patients with Liver Cirrhosis. Clinical Chemistry 2002;48:183-185.

9. Van der Griend R, Biesma DH, Haas FJLM, et al. The effect of different treatment regimens in reducing fasting and postmethionine-load homocysteine concentrations. J Int Med 2000;248:223-9.

10. Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol 1996;27:517-27.

11. Kraft K. Artichoke leaf extract- recent findings reflecting effects on lipid metabolism, liver and gastrointestinal tracts. Phytomedicine 1997;4:369-78.

12. Gebhardt R. Antioxidative and protective properties of extracts from leaves of the artichoke (Cynara scolymus L.) against hydroperoxide-induced oxidative stress in cultured rat hepatocytes. Toxicol Appl Pharmacol 1997;144:279-86.

13. Gebhardt R. Hepatoprotection with artichoke extract. Pharm Ztg 1995;140:34-7.

14. Adzet T, Camarasa J, Laguna JC. Hepatoprotective activity of polyphenolic compounds from Cynara scolymus against CCl4 toxicity in isolated rat hepatocytes. J Nat Prod 1987;50:612-7.

15. Vailati A, Aristia L, Sozze E, et al. Randomized open study of the dose-affect relationship of a short course of IdB 1016 in patients with viral or alcoholic hepatitis. Fitoterapia 1993; 64:219-27.

16. Lirussi F, Okolicsanyi L. Cytoprotection in the nineties: experience with ursodeoxycholic acid and silymarin in chronic liver disease. Acta Physiol Hung 1992; 80:363-7

17. Magliulo E, Gagliardi B, Fiori GP. Results of a double blind study on the effect of silymarin in the treatment of acute viral hepatitis carried out at two medical centers. Med Klin 1978; 73:1060-5.

18. Bode JC, Schmidt U, Durr HK. Silymarin for the treatment of acute viral hepatitis? Report of a controlled trial. Med Klin 1977; 72:513-8.

19. Schuppan D, Strösser W, Burkard G, Walosek G. Legalon® lessens fibrosing activity in patients with chronic liver diseases. Zeits Allgemeinmed 1998; 74:577-84.20. Campos R, Garido A, Guerra R, et al. Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Med 1989;55:417-419.

21. Valenzuela A, Aspillaga M, Vial S, Guerra R. Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. Planta Med 1989; 55(5):420-2.

22. Crinnion WJ. Environmental Medicine, Part 2 – Health Effects of and Protection from Ubiquitous Airborne Solvent Exposure. Alternative Medicine Review 2000; 5(2):133-143

23. Blumenthal M. Herbal Medicine, Expanded Commission E Monographs, 1st ed. Austin: American Botanical Council; 2000.

24. Brinker F. Herb Contraindications and Drug Interactions, 2nd ed. Sandy (OR): Eclectic Med; 1998.

25 Anonymous. N-Acetylcysteine: Monograph. Alt Med Rev 2000; 5(5); 467-471.

26. De Vries N, De Flora; S. N-Acetyl-l-Cysteine. J Cell Biochem 1993;17F:S270-S277.(-

...Continued on the next page.

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

28. Zimet I. Acetylcysteine: A drug that is much more than a mucokinetic. Biomed & Pharmacother 1988;42:513-520.

29. Packer L, Witt EH, Tritschler HJ. Alpha-Lipoic acid as a biological antioxidant. Free Rad Biol Med 1995;19:227-50.

30. Anonymous. Alpha-lipoic acid. Altern Med Rev 1998;3:308-10.

31. Packer L. Antioxidant properties of lipoic acid and its therapeutic effects in prevention of diabetes complications and cataracts. Ann N Y Acad Sci 1994;738:257-64.

32. Biewenga GP, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol 1997;29:315-31.

33. Bustamante J, Lodge JK, Marcocci L, et al. Alpha-lipoic acid in liver metabolism and disease. Free Rad Biol Med 1998;24:1023-39.

34. Vilas GL, Aldonatti C, San Martin de Viale LC, Rios de Molina MC. Effect of Alpha-lipoic acid amide on hexachlorobenzene porphyria. Biochem Mol Biol Int 1999;47:815-23.

35. Gurer H, Ozgunes H, Oztezcan S, Ercal N. Antioxidant role of alpha-lipoic acid in lead toxicity. Free Rad Biol Med 1999;27:75-81.

36. Altenkirch H, Stoltenburg-Didinger G, Wagner HM, et al. Effects of lipoic acid in hexacarbon-induced neuropathy. Neurotoxicol Teratol 1990;12:619-22.

37. Bone K. Clinical Applications of Ayurvedic and Chinese Herbs. Warwick, Queensland: Phytotherapy Press; 1996:126-30.

38. Luper S. A review of plants used in the treatment of liver disease: part 1. Altern Med Rev 1998;3(6):410-21.