Natural Alternatives to Hepatitis C

Continued from Part 1

OTHER PRODUCTS TO CONSIDER

In my research, I have found far more leads to follow than I have yet had

time to pursue. There is an almost bewildering array of possible products

and approaches for hepatitis C. I will summarize some of them here. I

would be grateful for any guidance on which might be the most important

ones to explore further, or any suggestions about other products that I

should be looking at.

I will list these items in alphabetical order. I have included among the

attached background papers some of the pieces that I have collected on

them. Where there are no background papers, I have left in the text some

of the references from my own notes.

* Aloe

Aloe vera juice, or capsules, are a popular product, to be found on the

shelves of most health food shops.

Aloe vera contains acemannan, which stimulates the production by

macrophages of monokines, including interleukin-1 and tumour necrosis

factor (not necessarily a good thing for hepatitis C.) Acemannan has been

observed to abrogate viral infections in animal and man. (Wombel,

Helderman, International Journal of Immunopharmacology, 1988, 10)

Aloe contains polysaccharides which display adjuvant activity on specific

antibody production. (t'Hart, van den Berg et al, Planta Medica Dec 1989)

It improves wound healing and, many studies have shown, inhibits

inflammation. (MedLine)

Of a group of mice with malignant sarcoma, all those not treated with

acemannan died, while 40% of those treated with acemannan survived. (Peng

et al, Mol Biother June 1991)

Aloe barbadensis contains anthraquinones, which inactivates the herpes

simplex virus type 1. A purified sample of aloe emodin was prepared from

aloin, and was found to inactivate the enveloped viruses herpes simplex

virus type 1 and type 2, varicella-zoster virus, pseudorabies virus,

influenza virus, but not adenovirus or rhinovirus. Electron microscopic

examination of the inactivated herpes virus showed the envelopes were

partially disrupted. This is thought to prevent virus absorption and

subsequent replication. In vitro tests found no evidence of toxicity of

aloe emodin to cells, even at high concentrations. (Sydiskis et al,

Antimicrobial Agents and Chemotherapy, Dec 1991.)

Since HCV is an enveloped virus, this ability of aloe to disrupt the

envelope of some viruses may be interesting. Its anti-inflammatory

qualities may be helpful with hepatitis. However, long-term use of

anthranoid-containing laxatives, such as aloe and rheum, may slightly

increase the risk of colorectal cancer in humans. Anthranoid laxatives

have been found to be somewhat carcinogenic in experiments in rodents.

Long-term abuse of anthranoid laxatives may also cause other health

problems. (Siegers et al, Gut, 1993.) There is some controversy on this

point. I include the Siegers article under "Other Herbal Products, etc."

Another cause for hesitation is the MedLine summary on aloe, which states:

"A genus of the family Liliaceae containing anthraquinone glycosides such

as aloin-emodin or aloe-emodin that cause gastrointestinal irritation,

purgation, and kidney damage. It was used formerly as a laxative and for

treatment of dermatitis."

* Amino acids

Arginine in pharmacologic doses appears to have a generally positive effect

on immune system functions and wound healing. It has been suggested as a

possible comlementary therapy for hepatitis C. (Kirk, Barbul, Journal of

Parenteral and Enteral Nutrition, 1990.) However, arginine has been shown

to strongly stimulate reproduction of herpes virus in people with cold

sores or genital herpes, which to my mind may be a reason not to consider

it as part of an anti-viral strategy without further research.

Glutamine, the most abundant amino acid in the body, also has immune

stimulant effects. (Alexander, Archives of Surgery, Nov 1993) It improves

anti-microbial killing by neutrophils isolated from the blood in vitro, and

in vivo. (Alexander) Patients receiving glutamine supplemented diets after

bone marrow transplant had reduced rates of infection. (Ziegler et al, Ann

Intern Med, 1992.)

N-acetyl-cysteine. In Dr. Bonkovsky's paper (referred to above) for the

U.S. National Institutes of Health Consensus Development Conference on

Management of Hepatitis C, he makes a brief reference to the amino acid

N-acetyl cysteine:

"Other approaches to treatment, such as the use of N-acetyl cysteine (NAC),

or other GSH donors, are based upon the knowledge that, in chronic

hepatitis C (as in other liver diseases), oxidative stress increases and

plasma and liver GSH concentrations decrease. Oral NAC ( 1800 mg/d),

although having little effect alone, enhanced the response to IFN. "

NAC is a "glutathione precurser." It is metabolized and converted in the

body into the amino acid glutathione (GSH), leading to higher levels of

glutathione in the liver.

Virtually all hepatitis C patients, says one hepatologist, have "severely

depressed" levels of glutathione. This deficiency might arise from the

immune system's ongoing struggle with the virus, or from the effort

required to repair cellular damage.

A briefing paper on the Internet says: "NAC (N-acetyl cysteine), an amino

acid, is a cysteine derivative which is necessary for the production of

intracellular glutathione (GSH)... In the United States it is used to

treat Tylenol (acetaminophen) overdose. NAC is known to have antioxidant

properties as well as anti-HIV activity, and is widely used by many people

with HIV...

"Glutathione (GSH) is an antioxidant essential for the proper functioning

of T-cells, natural killer cell activity, and cellular detoxification...

NAC replenishes and enhances intracellular levels of GSH and has been shown

to inhibit HIV replication in newly and already infected cells."

In a pilot study at the University of Navarra in Spain, in combination with

interferon treatment, 600mg of NAC was administered daily to 14 patients

who had not responded to interferon alone after four months of treatment.

The combination therapy for a further six months resulted in normalization

of ALT levels in 41% of these previously unresponsive patients, and ALT

reductions in all patients.

A 1996 summary in the "American Journal of Gastroenterology" of an Italian

study by Barbaro et. al. says:

"The systemic depletion of glutathione appears to be '...a factor

underlying the resistance to interferon therapy, and, in patients who are

HIV-positive, to antiretroviral drugs, fostering HCV and/or HIV

replication,' the authors say.

Based on these results, Dr. Barbaro suggests that glutathione replacement

therapy, possibly in combination with N-acetyl-cysteine, may be indicated.

In addition to enhancing response to interferon alfa in patients with

chronic hepatitis C, '...N-acetyl-cysteine has been shown to induce

antiretroviral effect in vitro and low toxicity in vivo; a combination of

N-acetyl-cysteine (or other GSH producing drug) with reverse transcriptase

inhibitors may prove to be a useful treatment for HIV infection and may be

effective in extending latency and delaying the development of

opportunistic infections.' "

It is not fully understood why NAC appears to help in treatment of

hepatitis C. Glutathione as an anti-oxidant may help to mop up the greater

quantities of damaging free radical molecules produced by the immune

response to HCV or by the cell damage the virus causes. Glutathione is

believed to assist in the detoxification of the liver. It may be an immune

stimulant or have direct anti-viral properties.

Glutathione also appears to have anti-cancer properties. An article in

1973 in "Science" magazine reported that in rats exposed to the chemical

aflatoxin B, which would normally produce liver cancer in 100% of cases,

when glutathione was also administered 80% were still alive and well after

two years.

In a 1995 article on NAC for lung cancer prevention, published by Dutch

researchers in the journal "Chest," the authors state:

"...This implies that carcinogenic compounds can initiate tumour growth

only in amounts saturating detoxification mechanisms. In this context it

is well known that glutathione plays a crucial role in the detoxification

of xenobiotics. NAC, an aminothiol and precursor of intracellular cysteine

and glutathione, has been shown to possess important preventative

properties."

Interestingly, there is recent research suggesting that bovine thymic

extracts can also boost levels of glutathione in patients.

Contradicting the doctor quoted earlier, however, Beloqui et al say in the

Journal of Interferon Research in 1993:

"N-acetyl cysteine (NAC), an antioxidant and glutathione source, has

been shown in one pilot study to induce response to interferon when

patients had previously failed to respond. However, most patients

with chronic hepatitis C are not glutathione deficient and the

therapy is expensive and distasteful. Controlled trials need to

determine if NAC has any effects in chronic hepatitis C."

NAC is available over the counter in many health food shops. The

recommended dose is 500-600mg 3X per day before meals. What is meant by

"the therapy is expensive and distasteful" I do not know. The question is:

is there any good reason not to take NAC when the research so far suggests

that it could be very helpful?

I am assuming there is so much discussion of NAC because taking glutathione

supplements directly, which might seem the obvious approach, presumably

doesn't lead to significantly raised levels of glutathione in the liver.

But this is speculation on my part.

* Bupleurum

Bupleurum is clearly an interesting herb for hepatitis C. I attach a set

of research abstracts from Medline, EMBase and from elsewhere on the

Internet.

As these abstracts show, Bupleurum has been found to have hepatoprotective

qualities when laboratory animals are given liver-damaging chemicals. It

has been shown to be an anti-inflammatory, appears to be an immune

stimulant, and inhibits formation of lipid peroxides in the liver. It is

thought to increase protein synthesis in the liver. Its known active

ingredients are a set of compounds called saikosaponins.

A clinical trial in Japan in 1981 found that oral administration of a

mixture of saikosaponins a and b at a low dose significantly reduced the

levels of serum transaminases in chronic hepatitis patients.

Sho-saiko-to (TJ-9):

Perhaps the most widely tested Bupleurum product in hepatitis is

Sho-saiko-to, otherwise known as Minor Bupleurum Combination, TJ-9 or in

Chinese Xiao Chai Hu Tang. This is a traditional herbal preparation

available as a pharmaceutical product in Asia, based on an ancient formula

of seven medicinal plants. The seven components are bupleurum, scute,

pinellia, fresh Ginger, ginseng, jujube, and glycyrrhizin (licorice).

Sho-saiko-to has been widely prescribed to chronic viral liver disease

patients in Japan.

.

Probably because it is a blend of medicinal plants, Sho-saiko-to is

believed to have a wide range of activity in test tube and animal studies

that can be broken down into three main categories: 1)

anti-oxidant/anti-inflammatory effects, 2) immune stimulating effects, and

3) anti-viral/tumor effects.

One summary of Sho-saiko-to says: "There have been several studies of SSKT

for hepatitis B, although none were well designed. One six month study in

80 people with chronic hep B reported decreases in viral load, antigen and

50%

improvements in liver function. Another study in twenty six

patients with chronic hep B reported even better results in

eleven of the participants treated with SSKT. Seven out of

fourteen children with chronic hep B cleared antigen within six

months in yet another study of SSKT." The latter reference is to a

clinical trial carried out among children with hepatitis B in Japan in

1991.

In a study in Japan, reported in 1995, following cirrhosis patients for

five years, the group taking Sho-saiko-to had a higher survival rate and a

lower rate of liver cancer than the control group.

A 1996 study in Japan found that Sho-saiko-to inhibited liver fibrosis in

rats "not by cytoprotection but by direct inhibition of stellate cell

activation in rat liver cirrhosis."

One study examined the inductions of such cytokines as interleukin-1 beta

(IL- 1 beta), tumor necrosis factor-alpha (TNF-alpha), and granulocyte-

colony stimulating factor (G-CSF), on some fractions of peripheral blood

mononuclear cells (PBMC) by Sho-saiko-to and each of its seven components.

IL-1 beta, TNF-alpha, and G-CSF were highly induced by scutellaria root and

glycyrrhiza root on monocytes/macrophages.

I have seen a reference on the Internet to a study in 1994 which found that

"76.7% of patients with HCV improved in short term on Xiao Chai Hu Tang

(Minor Bupleurum) and Gan Yan Chong Ji (China)," but at this stage I have

no further information on the study.

Side effects from taking Sho-saiko-to are said to be rare. However, there

are a few documented cases of SSKT causing lung inflammation in elderly

patients. The Japanese government has recently instructed manufacturers to

include in the package insert a warning that it can cause interstitial

pneumonia, which is sometimes fatal. Though such cases are very unusual,

this may be a reason not to use it unless there is a strong reason to. It

is not yet known what the mechanism of causation is in these cases - or

which of the herbs may be involved.

The package insert also states that SSKT should not be used in combination

with interferon-alpha.

Ses Salmond, a herbal practitioner in Australia, says "it may increase

bowel movements and flatulence (wind)." Elsewhere I have read that it may

cause nausea in some patients, and therefore it is best to start with small

amounts. One summary by a non-expert remarks, without explanation, that

"Sho-saiko-to boosts G-CSF, and gamma-interferon (and maybe some harmful

cytokines too)."

The only other possible grounds for hesitation I have seen is a Medline

record of an article, without an abstract available online, titled:

"Pharmacological studies on Bupleurum falcatum L. I. Acute toxicity and

central depressant action of crude saikosides". What this article refers

to I have no idea, though it might conceivably refer to toxicity tests at

very high doses.

* Cod liver oil / Evening primrose oil

Omega-3 fatty acids, found in fish oils and I believe also in evening

primrose oil among other products, enhance cell-mediated immune responses,

increase resistance to infection, and inhibit inflammatory diseases.

(Alexander, Arch Surg 1993)

One cause for hesitation with fish oil is that traces of PCBs have been

found in cod liver oil. Given the pollution of our seas with long-lived

organic pollutants, I daresay there are other unwelcome ingredients. Where

the fish comes from apparently makes a difference: for example, fish from

around Iceland contain less PCBs than from the Baltic. (MedLine)

* Colchicine

In his "Hepatitis C Handbook," Matthew Dolan says: "Colchicine is an

extract from the bulb of the meadow saffron plant (Colchicum autumnale),

and has been tested in combination with interferon in Italy by doctors at

the University of Pisa. They concluded that its use was 'associated with a

lesser rebound of viraemia.' " I have not yet looked into it further.

* Garlic

Garlic appears to have both immunostimulant and virucidal qualities.

In various studies, fresh garlic extract was virucidal to: herpes simplex

virus 1 and 2; parainfluenza 3 virus; vaccinia virus; vesicular stomatitis

virus; human rhinovirus 2; human cytomegalovirus. (MedLine)

Garlic has been found to enhance the immune system, increasing numbers of

natural killer cells. Dr. Andrew Weil, in his bestselling book

"Spontaneous Healing", adds: "Miscellaneous effects of garlic include

protecting liver and brain cells from degenerative changes." He recommends

eating more fresh garlic, rather than taking concentrated garlic

supplements.

The research gives a slightly mixed impression concerning garlic and

cancer. Selenium-enriched garlic was found to reduce breast cancer.

(MedLine) One study suggested that garlic may help to prevent gastric

cancer. However, some constituents of garlic and onions seemed in one

study to promote liver cancer in rats. (MedLine) Toads fed garlic, on the

other hand, appeared to have a lower incidence of liver cancer. (MedLine)

Another possible reason for eating fresh garlic and avoiding concentrated

garlic supplements is that it is well known - and indeed I know from my own

experience of taking garlic supplements - that large doses of garlic can

reduce blood pressure quite sharply.

* Ginger (Zingiber officinale)

Doctors in China and India have regarded ginger as a superior medicine for

centuries, and Dr. Weil is enthusiastic about it in his book. Among other

well-researched actions of ginger, it is said to modulate the body's

production of eicosanoids (prostaglandins, thromboxanes, leukotrienes) in

ways that reduce abnormal inflammation. It might thus help to reduce

inflammation of the liver due to hepatitis.

I recall that some researchers have suggested that one of the mechanisms by

which milk thistle protects the liver is its ability to regulate

leukotriene activity.

* Ginseng, Siberian

Animal and human studies have found that Siberian ginseng (Eleutherococcus

senticosus) is an immune stimulant. It is also claimed to be an interferon

inducer. Like many other items on my list (such as astragalus, echinacea

and lentinus edodes) its active ingredients include polysaccharides, as

well as a group of compounds called eleutherosides.

Siberian ginseng has become popular as a general tonic. Dr. Weil

recommends buying extracts that have been standardized for eleutheroside

content, and says that Siberian ginseng "can be used safely over long

periods of time."

Siberian ginseng is a genus in the ginseng family. The more traditionally

used ginsengs are Panax ginseng, native to northeastern China, and Panax

quinquefolium, native to northeastern North America. Panax quinquefolium

has been suggested as a possible general tonic for hepatitis C patients,

but Panax ginseng is not recommended, and may even exacerbate hepatitis C

symptoms.

* Globe artichoke (Cynara scolymus)

Artichokes are often claimed to be a general tonic for the liver. They are

believed to be a cholagogue (promoting bile production), and to stimulate

the regeneration of liver cells. I include some information under "Other

Herbal Products, etc", but have not yet looked into it in detail.

* Herbs, other

There is a fair amount of laboratory and clinical research being done -

particularly in China, Taiwan and Japan - on traditional herbal treatments.

Professor Batey at the John Hunter Hospital in Australia has recently

carried out a trial of a Chinese herbal preparation on hepatitis C

patients. The formulation he used improved liver function in a number of

patients, though it did not eliminate the virus. I understand that he has

not yet been able to publish the results.

I have seen a reference to a report in the Chinese Journal of Integrated

Traditional and Western medicine (1994), which claimed a "rate of cure" of

56%, with most other patients showing improvements, when the following

formula was administered to treat hepatitis C:

astragalus: 30 grams

salvia: 30 grams

forsythia: 30 grams

red peony: 30 grams

ho-shou-wu: 15 grams

crataegus: 15 grams

moutan: 15 grams

gardenia: 15 grams

dandelion: 15 grams

bupleurum: 10 grams

The fruits of Schizandra chinensis and related plants have been used in

Japan and the Orient for the treatment of patients with liver disease.

Here is a summary of a 1979 trial:

"Schizandra given to 189 patients manifesting chronic viral hepatitis with

elevated serum GPT levels. 107 were given 100 mg. of the extract (= 1.5 g

of the herb) 82 cases received a liver extract-vitamin E complex as

control. After 16-24 weeks of treatment, 73 of those treated with

Schizandra showed a fall of serum GPT to normal levels. No rebound was

observed after withdrawal of the herb. The rate of effectiveness in

lowering the GPT level was 68.2% in the treated group and 44% in the

control group. The average time needed for lowering the level to normal was

about 4 weeks for the treated group and 8 weeks for the control group.

Schizandra was effective in relieving symptoms of sleeplessness, fatigue,

abdominal tension, and loose bowels. No side-effects were observed."

In a number of animal studies, Schizandra has improved liver function after

liver damage.

Under "Other Herbal Products, etc," I have included as attachments reports

on research that found the following herbs and herbal preparations to have

hepatoprotective effects. These studies often involved medical researchers

giving hepatotoxic compounds to laboratory animals to cause liver damage,

then giving them the herbal product, and finding improvement in the treated

group versus the controls in liver function tests and/or in histological

tests. These products included:

* Huanglian-Jie-Du-Tang (HLJDT), a Chinese medicinal prescription,

* Bidens pilosa L. var minor (Blume) Sherff, B. pilosa L. and B. chilensis

DC (compositae), commonly known as ''Ham-hong-chho'' in Taiwan,

* 'Teng-Khia-U' , a folk medicine of Taiwan, derived from the entire plants

of Elephantopus scaber L., E. mollis H.B.K. and Pseudoelephantopus spicatus

(Juss.) Rohr

* Salvia plebeia R. Br., Ocimum gratissimum L., and Ocimum basilicum L.

(Labiatae), used in a Taiwan herbal remedy named 'Chhit-Chan-Than',

* a Taiwanese crude herb, Hwang-hua-mih-tsay (Wedelia chinensis (Osbeck) Merr.),

* a Taiwan folk medicine: Ixeris chinensis (Thunb.) Nak.

* Bombax malabarica and Scutellaria rivularis.

A trial was carried out in California of a Chinese herbal formula, with its

main component Picrorrhiza root, in patients with active or chronic

hepatitis. I do not have the results.

An Australian herbal practitioner, Ses Salmond, listed a number of herbs

she recommends for hepatitis C. I include her summary of the properties,

medical uses, modes of action and side effects of each one among the

attachments under "Other Herbal Products, etc." They include:

BOTANIC NAME Berberis vulgaris

COMMON NAME Barberry

BOTANIC NAME Chelidonium majus

COMMON NAME Greater Celandine

BOTANIC NAME Desmodium ascendens

COMMON NAME Desmodium

BOTANIC NAME Picrorrhiza kurroa

COMMON NAME Picrorrhiza

BOTANIC NAME Schisandra chinensis

COMMON NAME Schisandra

BOTANIC NAME Taraxacum officinale

COMMON NAME Dandelion root

The "Hepatitis C Handbook" by Matthew Dolan draws attention to a number of

potentially interesting herbs, including the following:

Cat's Claw (Uncaria tomentosa) is said to be a good immune stimulant, as

well as having anti-inflammatory and anti-oxidant properties.

Desmodium (Desmodium axcendens) may help to normalize ALTs and prevent

cirrhosis.

Oregon grape root (Mahonia aquifolium or Mahonia repens) is a popular herb

for treating chronic hepatitis, often combined with dandelion root.

Pau d'Arco (Tabebuia, Lapacho or Tabebuia heptaphylla) from South America

has attracted attention as a possible cancer treatment, and may be helpful

to hepatitis C patients for its immune boosting and digestive tonic

qualities.

Peony root (Paeonia lactiflora) is considered a liver tonic.

Sarsaparilla (Sarsaparilla officinalis) is used to treat hepatitis,

containing saponins (perhaps related to the saikosaponins which are an

active compound in Bupleurum.) It is said to have anti-inflammatory

properties.

Wild yam (Dioscorea paniculata) is prescribed to some chronic hepatitis

patients, and is thought to be an anti-inflammatory and a cholagogue.

Yellow dock (Rumex crispus) is often used by Western herbalists in the

treatment of liver disease. It is said to decongest the liver, reduce

inflammation and increase bile flow.

There is no shortage of herbal combinations on the shelves of the health

food shops. Without any training, it is difficult to assess which might be

of most interest. Here, for example, is one called ThistleRex:

Description:

PhytoPharmica, 60 capsules per bottle

Each capsule contains:

Milk Thistle Extract (standardized to contain 80% Silymarin, 120

mg. calculated as silybin), 150 mg.

Dandelion Root Extract 4:1 (Taraxacum Officinalis), 10 mg.

Artichoke Leaves Extract (Cynara Scolymus), 10 mg.

Licorice Root Extract (Glycyrrhiza Glabra standardized to contain

5% Glycyrrhetinic acid), 10 mg.

A preparation called Hepatofalk, containing extracts of Silybum marianum,

Chelodonium majus and Curcuma xanthorrhiza, is being used increasingly in

Germany for the treatment of chronic liver disease.

Mistletoe may be of some interest, since Swiss medical researchers have

remarked that its immunostimulant effects are not unlike those of

interferon-alpha. Indeed, Prof. Saller at the University of Zurich Medical

School told me that it has been found to induce alpha-interferon, both in

vitro and in some small in vivo studies of cancer patients. Mistletoe may,

however, have some undesirable side effects. I have not yet looked into

this.

I deal with licorice root and phyllanthus in separate sections below.

* Hypericin / Hypericum perforatum (St John's Wort)

In the attachments under "Other Herbal Products," I have included a couple

of pieces on hypericin. Hypericin is a natural product derived from the

plant Hypericum perforatum (St John's Wort). It appears to have strong

anti-viral properties against HCV, and may be one of the most promising new

therapies for hepatitis C.

The pharmaceutical company VIMRx is at this moment conducting a trial, in

patients with hepatitis C, of a synthetic hypericin which they have

developed, brand-named VIMRxyn.

A review of the literature on natural hypericin done at the University of

Exeter found no reports of severe side effects. Hypericin can at high

doses increase the skin's sensitivity to sun. This side effect was

experienced quite unpleasantly by patients in early trials with synthetic

hypericin. Since then, dose ranging trials have been carried out to

determine the tolerable doses.

As I mentioned earlier, my main reason for waiting on hypericin is to avoid

enabling the virus to develop resistance in response to low doses, which

might then undermine the effectiveness of the higher therapeutic doses that

may soon be available if the VIMRx trial produces good results.

There are only two other possible questions about hypericin. One comment I

have seen on the Internet said: "I have recently read in "How to Reverse

Immune Dysfunction" by Nielson, RN, Dr. Robert Carson, MD, and Dr.

Cantwell, MD, that St. John's Wort was shown to have caused liver enzymes

to elevate in some patients." I have not looked into this.

I also note that hypericin is a naphthodianthrone. Having little training

in chemistry, I have wondered if there might be the same concern about its

long-term use as there is with anthranoid laxatives such as aloe: that it

could increase the risk of colon cancer. I put this question to the

research director at VIMRx, and he was good enough to confess that he has

unaware of the study on anthranoids and couldn't make any useful comment on

this. However, since it is controversial whether there is in fact any risk

at all from aloe etc, and if there is it is a very low risk, I certainly

wouldn't consider this a reason not to pursue a course of hypericin as a

treatment for hepatitis if it shows promise.

HepC BC