Hepatitis C Choices in Care

Nutrition, Supplementation and Hepatitis C

Lyn Patrick, ND

What is Naturopathic Medicine?

The philosophy of naturopathic medicine can best be described as the utilization of the healing

power of nature.

All of the components of wellness are

equally important !!!

What is Naturopathic Medicine?

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

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 drugsregular exercise stress management

While these practices are helpful with any therapeutic approach, they are vital to the success of naturopathic treatment.

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.

Limiting Exposure to Liver-Damaging Substances and SituationsThe 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.

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.

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.

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.

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 an antioxidant.

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

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.

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

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):367-374Yu SYBiol Trace Elem Res. 1997;56(1):117-124.

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.

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

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

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.

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.

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

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

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.

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)

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

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.

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.

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

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-carnosine chelate)-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.

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;55:2624Gastroenterol Heptol 2010;6:491.Hepatology 2010;51:1158.

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)

AASLD 2009 – Abu-Mouch S, Israël, Abstract LB20 actualisé

HCV RNA undetectable(< 50 IU)

Placebo + PEG-IFN/RBV

Vitamin D + PEG-IFN/RBV

100

80

60

20

0S4 S12

96 %

48 %44 %

18 %

40

%

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 txvs 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

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;10:68J Gastroenterol Hepatol 2006;21(1 pt2):275.Aliment Pharmacol Ther 2011;333:127

Silymarin and HCV

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

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.

Zinc in HCV and Progression to Cirrhosis

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)

S-adenosylmethionine (SAMe)

Physiologic compound involved in transmethylation and transsulfuration occuring 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.

S-adenosyl methionine (SAMe)

SAMe has 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.

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

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;292:3582.Vitam Horm 2008;78:435.

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 yearsNutr Cancer 2009;61:789.

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 Fam Phys 2001;64:1555.

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

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

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

Drugs that may lead to Cholestasis

Natural and synthetic steroid hormones (OCP, anabolic steroids, HRT) Antibiotics Diuretics NSAIDs Thyroid hormone (T4)

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)

Appreciation and Acknowledgement Lorren Sandt Program Director

Hepatitis C Caring Ambassador Program Oregon City, OR

Robert Gish MD University of California, San Diego School of Medicine Co-Director Center for Hepatobiliary Disease and Abdominal Transplantation San Diego, CA

Stewart Cooper MD Director Liver Immunology Laboratory at California Pacific Medical Center San Francisco, CA

Misha Cohen OMD. LAc Assistant Researcher for Integrative Medicine at the UCSF Institute for Health and Aging San Francisco, CA