Hepatitis C Choices in Care

1. Hepatitis C Choices in Care Nutrition, Supplementation and Hepatitis C Lyn Patrick, ND

2. What is Naturopathic Medicine? The philosophy of naturopathic medicine can best be described as the utilization of the healing power of nature.

3. All of the components of wellness are equally important !!! What is Naturopathic Medicine?

4. What is Naturopathic Medicine? • Naturopathic healthcare providers use many different tools in the care and treatment of patients. • These include: • botanical medicines (herbs) • acupuncture • nutritional supplements • traditional Chinese medicine • homeopathic remedies • nutrition counseling and diet therapy • massage and/or spinal manipulation • exercise • and other forms of therapy

5. Naturopathic Medicine and Who May Benefit Naturopathic treatment options may benefit those who are motivated to adopt the following healthy lifestyle practices including: • a nutritious diet low in sugar, red meat, and processed foods • avoidance of smoking, alcohol, and recreational drugs • regular exercise • stress management While these practices are helpful with any therapeutic approach, they are vital to the success of naturopathic treatment.

6. Limiting Exposure to Liver-Damaging Substances and Situations Alcohol Alcohol consumption is a significant risk factor for liver cirrhosis. Tobacco and Recreational Drugs Both tobacco and marijuana use increase the risk of liver cancer for people infected with HCV Occupational Exposures Exposure to pesticides, herbicides, and other chemicals can cause liver damage and elevation of liver enzymes.

7. Limiting Exposure to Liver-Damaging Substances and Situations The potential for drug-herb interactions in people with liver disease is complex and often unpredictable. Keep all of your healthcare providers informed about all medicines, herbs, and supplements you are taking. Never take any medicinal product if you are uncertain about what it contains.

8. Why are Antioxidants Important in Hepatitis C ? Cellular damage occurs in an environment that is high in free radicals and low in antioxidants. • This causes cellular damage (inflammation and fibrosis) that occurs as a result of the interaction between the hepatic immune cells and the viral infection.

9. Antioxidants and Fibrosis Blood levels of the antioxidants glutathione, vitamin A, vitamin C, vitamin E, and selenium are much lower in HCV+ persons when compared to people the same age and sex who do not have hepatitis C. Sanjiv KJ, et al. J Hepatol 2002;36:805-811.

10. Antioxidants in Hepatitis C • Glutathione is the main antioxidant in liver and all mammalian tissue. • Glutathione is a sulfur-containing protein that is used in detoxification, immune function, and antioxidant protection in the liver as well as all tissues in the body. • Glutathione levels are low in people with hepatitis C.

11. Glutathione and Antioxidants • Vitamins E and C, alpha-lipoic acid, selenium, and co-enzyme Q help recycle glutathione so it can continue to work as an active antioxidant, detoxification protein, and immune stimulator. • Silymarin has been shown to raise liver glutathione levels 35%, and is more potent than vitamin E as anantioxidant.

12. Antioxidants and Fibrosis • Markers of oxidant stress in those with HCV and low antioxidant levels were closely connected to the amount of fibrosis in the liver. • The higher the oxidant stress, the more advanced the fibrosis. Fibrosis was also connected to low levels of antioxidants in the blood. Sanjiv KJ, et al. J Hepatol 2002;36:805-811

13. Antioxidants and Fibrosis • Those in the study with significantly elevated ALT levels (over 100) had the most significant vitamin E deficiencies. • Genotype 1b had the lowest glutathione levels of all genotypes.

14. Vitamin A • High doses of supplemental vitamin A can be toxic to the liver. • Supplements may be necessary in cases of vitamin A deficiency • It is safer to supplement with beta-carotene or mixed carotenoids. • A safe dose of vit. A is 10,000-25,000 IU daily

15. Selenium and Liver Cancer • In a study of 7,342 men with HBV or HCV, those with the highest selenium levels were 40% less likely to get liver cancer than those with the lowest levels. • 200 mcg of yeast-based selenium decreased the incidence of liver cancer in HBV endemic area of China by 33%. • Selenium deficiencies more significant in co-infection (HIV/HCV). • Selenomethionine or yeast-based selenium is safest and most absorbable. • A safe dose of selenomethionine is 200 mcg. daily Yu MWAm J Epidemiol. 1999;150(4):367-374 Yu SYBiol Trace Elem Res. 1997;56(1):117-124.

16. Zinc • Zinc has been shown to be one of the nutrients that may be deficient in those with hepatitis C. • Zinc may be useful in the prevention and treatment of hepatic encephalopathy.

17. Zinc • Zinc is less absorbable in those with cirrhosis. • Zinc is twice as absorbable in those with cirrhosis when taken between meals. • Zinc citrate, picolinate, septahydrate are more absorbable than zinc oxide, gluconate, or sulfate. • A safe dose of zinc is 30-60 mg. daily • Those with cirrhosis may need higher doses

18. Vitamin E • Fat soluble vitamin found in oils, cereal grains, animal fats, fruits, and vegetables. • Naturally occurring vitamin E consists of a complex of 8 different forms found in foods: • alpha-tocopherol • beta-tocopherol • gamma-tocopherol • delta-tocopherol • 4 types of tocotrienols

19. Vitamin E • Most of the vitamin E found in food is gamma-tocopherol. • Most of the commercially available vitamin E and the form used in many studies is synthetic L-alpha tocopherol isomer (not the d-form). • The forms used in the recent meta-analysis were not disclosed but can be assumed to be alpha-tocopherol only and probably the L-isomer.

20. Vitamin E Synthetic vitamin E (l-alpha tocopherol with no other tocopherols or tocotrienols) has ability to bind to receptor sites, potentially in favor of biologically active forms of vitamin E (d-alpha-, beta-, delta-, and gamma-tocopherol) and may even be harmful.

21. Vitamin E • May improve response to interferon. • 1200 IU for 8 weeks in HCV+ completely blocked the biochemical pathway leading to fibrosis. • Vitamin E at 1200 IU is contraindicated in coumadin therapy and with vitamin K deficiency. • Look MP, et al. Antiviral Res. 1999;43(2):113-122. • Houglum K Gastroenterology. 1977;113(4):1069-1073

22. Alpha-Lipoic Acid (ALA) • ALA has been used to treat diabetic peripheral neuropathy and acute liver failure in Europe. • Because it is active in both fatty tissue and non-fatty tissue, it has a wide range of activity as an antioxidant. www.voy.com/17059/190.html for an interview with Lester Packer PhD, ALA researcher

23. ALA raises Glutathione Levels in Humans with Low Glutathione • ALA is effective at a lower molecular concentration and a lower dose than NAC: • 450 mg raised glutathioine levels in HIV+ in 14 days • Doses of 600 mg equivalent in animal and in vitro studies have raised glutathione levels significantly. Fuchs J, et al. Arzneimittelforschung 1993;43:1359.

24. S-Adenosyl Methionine (SAMe) • Used in Europe to normalize bile secretion in chronic liver disease. • Studies in HBV and HCV showed reduction of itching, jaundice, fatigue, and lowering of bilirubin in median of 16 days. • Dosages used: 800-1600 mg daily • Difficulties: cost and storage (easily oxidized)

25. Enhancing Response to Treatment • SAMe and betaine- improve interferon’s effect in presence of HCV • a cohort of 29 HCV +( 80% genotype 1, 72% cirrhotic) who had previous non-response to standard therapy were given • SAMe 400 mg tid • Betaine 3 g bd (anhydrous) One week lead-in and then 24 wks standard therapy with pegINF and ribavirin • PLoS ONE 5(11):3 15492. doi: 10.1371/journal.pone.0015492

27. Preventing Side Effects During Treatment-HCV • EPA- 1.2 grams daily • Vit. C- 600 mg. daily • Vit. E- 300 IU daily • Prevented low white cell counts, T-helper 1 decline and improved 48 week red blood cell iron levels Lipids 2008;43:325.

28. Preventing Side Effects During Treatment: HCV • 500 IU E, 750 mg C • able to prevent drop in EPA levels in RBCs indicating a decreased risk for hemolytic anemia from ribavirin Nutrition 2006;22:114.

29. What I Use • Vit. E- 1000 IU mixed tocopherols • Vit. C- 3000 mg bd or 2000 mg td • EPA- 1.2 gm from krill oil • why krill?- astaxanthin BUT expensive so use a good mercury-free PCB-free fish oil if money is an issue

30. Preventing Side Effects During Treatment • Zinc (zinc/L-carnosine chelate)- 150 mg. decreased gastrointestinal side effects during 48 week course of peg-interferon/ribavirin treatment. • Zinc (zinc/L-carnosinechelate)-in addition to 300 IU vit. E and 600 mg vit. C improved both EVR at 12 wk and at 48 wk and prevented anemia due to treatment World J Gastroenterol 2006;12:1265.

31. Vitamin D Levels • Deficiency is common: 93% of patients in liver disease clinics have been found to be vitamin D deficient, African-American females and those with cirrhosis have highest risk • Low vitamin D levels are related to: • Poor response to standard treatment • Increased risk of fibrosis Dig Dis Sci 2010;55:2624 GastroenterolHeptol 2010;6:491. Hepatology 2010;51:1158.

32. Vitamin D: Impact on virologic response • Randomized Study, 58 patients G1, treatment naïve • PEG-IFN-2b (1.5 mcg/kg) + RBV (1000-1200 mg) + Vit D (1000-4000 IU)(27 patients, median age 47, 50 % male, 55 % > F2) • PEG-IFN-2b (1.5 mcg/kg) + RBV (1000-1200 mg) + placebo(31 patients, median age 49, 60 % male, 18 % > F2) HCV RNAundetectable(< 50 IU) 100 96 % 80 Placebo + PEG-IFN/RBV 60 48 % 44 % % VitaminD + PEG-IFN/RBV 40 18 % 20 0 S4 S12 AASLD 2009 – Abu-Mouch S, Israël, Abstract LB20 actualisé

33. Improving Outcome on Treatment: Phosphatidylcholine in HCV • In monotherapy trial of interferon alpha 2a or 2b x 24 wks: • treatment with 1.8 g of PPC during and 24 wks post tx: • significant improvement in biochemical response vs interferon alone (71% vs. 56%) • significant improvement in sustained response 24 wks post tx vs interferon alone (41% vs 15%) NO effect on biochemical response or viral clearance in HBV Conclusion: PPC may be recommended in interferon monotherapy during and after tx to reduce relapse rates • Hepatogastroenterology 1998;45:797

34. Silymarin and HCV • evidence that it does not improve ALT levels even on 1260 mg day • BUT silymarin use in 367 patients in a large group(HALT-C trial): • less fibrosis at beginning • less histological progression than non-users in the following 8.65 years (HR .57) Eur J Res 2005;10:68 J GastroenterolHepatol 2006;21(1 pt2):275. Aliment PharmacolTher2011;333:127

35. Silymarin and HCV

36. Probiotics • Probiotics have been shown to reverse fatty liver disease in animal models and decrease portal hypertension in isolated cases of cirrhosis • Probiotics (plus fiber called fructooligosaccharides = synbiotics) work as well as lactulose in those with cirrhosis who have hepatic encephalopathy

37. Acetyl-L-carnitine • An amino acid found in food (meat) • Acetyl-L-carnitine has also been shown to be effective in treating minimal hepatic encephalopathy • dosage: 2 g bd Dig Dis Sci 2008;53:3018.

38. Zinc in HCV and Progression to Cirrhosis

39. Zinc in HCV and Progression to Cirrhosis • Zinc carnosine (Polaprezinc) = 34 mg. elemental zinc qd • Significantly lower incidence of hepatocellular carcinoma • Slower fibrosis progression • In those on zinc who had increase in blood levels • Conclusions: weight-based dosing (.6 mg/kg)

40. S-adenosylmethionine (SAMe) • Physiologic compound involved in transmethylation and transsulfurationoccuring primarily in the liver. • Parenterally and orally (1600 mg. daily) effective for treating cholestasis of chronic liver disease SAMe oxidizes- that’s why it’s sold only in blister paks in Europe, should be the same way in U.S. Frezza M. Gastroenterol 1990;99:211.

41. S-adenosyl methionine (SAMe) • SAMehas been shown to delay the need for liver transplantation and reduce mortality in patients with alcoholic cirrhosis in a 24-month trial • Overall mortality/liver transplantation was 12% on SAMe versus 29% in placebo group. • Those with hepatitis C had a survival risk ratio of 4.5 compared to placebo. • Oral administration of 1200 mg. SAMe daily has been shown to significantly increase hepatic glutathione levels in nonalcoholic liver disease. J Hepatol. 1999;30(6):1081-1089. Scand J Gastroenterol 1989;24(4):407.

42. SAMe • Studies in patients with chronic hepatitis B and chronic hepatitis C have shown reduction of itching, jaundice, fatigue, and lowering of bilirubin in median 16 days. • Dosages used: 800-1600 mg. daily • Difficulty- cost, oxidizes easily

43. vit. K2- menaquinone • 40 women with HCV and cirrhosis: 21 on vit. K2 45 mg. qd compared to 19 on no treatment • 8 years later-risk of getting HCC with vit. K2 was reduced by 80% 1 Vit. K has also been found to suppress HCC recurrence in patients with prior diagnosis of HCC.2 1.JAMA 2004;292:358 2.Vitam Horm 2008;78:435.

44. Carotenoids/Myo-inositol • Randomized, controlled study HCC prevention in chronic hepatitis with cirrhosis: ( 24 treated vs 45 matched controls) • 1 gram myo-inositol and 3 grams β-cryptoxanthin as 190 ml mandarin orange juice • 10 mg. lycopene, 6 mg β-carotene, 3 mg α-carotene, 50 mg α-tocopherol, 1 mg. other carotenoids • for 2.5 years Nutr Cancer 2009;61:789.

45. Supplement Precautions • High doses of supplemental vitamin A can be toxic to the liver in HCV infection but may be necessary in cases of vitamin A deficiency (advanced cirrhosis) • Patients with chronic liver disease should consume less than 25,000 IU of vitamin A per day. • Iron should be avoided in any supplemental form altogether unless anemia is present. Riley T. Am FamPhys 2001;64:1555.

46. Role of Diet in Chronic Hepatitis C Management • protein: increased need in chronic liver disease • fat: saturated vs. unsaturated, high in omega-3, minimal trans fatty acids • insulin resistance common: multiple small meals with complex COH J Nutr Met 2010; doi:10.1155/2010/489823

47. Protein • 1.2-1.5 gm/kg/day in chronic liver disease without cirrhosis (average 150 lb. adult = 70-100 gms/day) • 1.0 gm/kg/day with severe hepatic encephalopathy but only for short period of time • short-term low protein diet (20-60 grams/day) if acute encephalopathy occurs, only for 2-3 days to control ammonia • animal vs vegetable- 71 grams/day vegetable improved metal status of cirrhotics with hepatic encephalopathy J Intern Med 1993;233(5):385

48. Fats/Digestive Support • Cholestasis is common in chronic hepatitis C and results in loss of ability to concentrate bile salts: fat malabsorption, fat-soluble vitamin deficiencies and steatorrhea • Lipase-containing digestive enzymes (pancreatin) can aid malabsorption: Lipase 2000-4000 NF in 500-1000 mg. pancreatin

49. Drugs that may lead to Cholestasis • Natural and synthetic steroid hormones • (OCP, anabolic steroids, HRT) • Antibiotics • Diuretics • NSAIDs • Thyroid hormone (T4)

50. Western Botanicals Used In Hepatitis C • Curcumin- unhibits fatty liver and fibrosis in animal models • Green Tea (EGCG)- decreased fatty liver when fed at human weight equivalent of 7 ounces (whole plant powder) • Shown to inhibit fibrosis in animal or cell models: resveratrol, quercitin, silymarin, Scutellaria (Skullcap)