Liver Degenerative Disease

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Liver Degenerative Disease

 

When compared to other health conditions, it is

striking how little attention is given to diseases of

the liver, particularly considering the rising level

of concern about health and health-related

environmental issues. Hepatoprotection (or protection

of the liver) is a subject that should be of intense

interest because the liver plays a critical role in

all aspects of metabolism and overall health.

 

This protocol will present intriguing information

about the role of the liver and explain why a

well-functioning liver is essential for overall

health. Also identified will be environmental hazards

that constantly challenge the detoxification capacity

of the liver. Research on the effects of alcohol on

the liver will be discussed. Additionally, you will

learn what you can do to support and optimize the

function of your liver and thus optimize your future

health and quality of life.

 

Some beneficial herbs will also be described. In

Europe and Asia, herbal liver tonics have been in

common use for decades--perhaps even for centuries.

The effectiveness of the herbs used in these remedies

has been validated during the past several decades

through research and clinical studies. These herbs

generally contain antioxidants; membrane-stabilizing

and bile-enhancing compounds; or substances that

prevent depletion of sulfhydryl compounds, such as

glutathione.

 

WHAT DOES THE LIVER DO?

 

The liver is located on the right side of the body in

the upper abdomen. In the human, it is the second

largest organ of the body, weighing about 4 lbs (skin

is the largest organ). Even while being exposed to

tremendous potential for damage, the liver performs a

multitude of essential functions: metabolizing,

detoxifying, and regenerating. It does an

extraordinary job of keeping us alive and healthy by

metabolizing the food we eat, that is, breaking it

down into useful parts, and by having detoxifying

abilities that protect us from the damaging effects of

numerous toxic compounds that we are exposed to on a

daily basis. Several times each day, our entire blood

supply passes through the liver. At any given time,

about a pint of blood is in the liver (or 10% of the

total blood volume of an adult) (NIDDK 2000). In

addition, the liver has impressive restorative

capabilities and is the only organ in the body that is

capable of regenerating itself when part of it has

been damaged.

 

The metabolizing functions of the liver are numerous.

The liver is intricately involved in carbohydrate,

fat, and protein metabolism; in the storage of

vitamins and minerals; and in many essential

physiological processes. The liver is also involved in

several regulatory mechanisms that control blood sugar

levels and hormone levels. It synthesizes proteins

(such as plasma albumin, fibrinogen, and most

globulins) and lipids and lipoproteins (phospholipids,

cholesterol), as well as bile acids that are excreted

in the detoxification process (NIDDK 2000).

 

Other important functions of the liver include

production of prothrombin and fibrinogen (two

blood-clotting factors) and heparin (a

mucopolysaccharide sulfuric acid ester that helps

prevent blood from clotting within the circulatory

system). The liver also processes glucose into

glycogen and stores it until the muscles need energy;

some glucose is also converted into fat and stored.

The released glycogen becomes glucose in the

bloodstream.

 

Additionally, the liver produces and secretes bile

(stored in the gallbladder), that is needed to break

down and digest fatty acids, and produces blood

protein and hundreds of enzymes needed for digestion

and other bodily functions. As the liver breaks down

proteins, it produces urea, which it synthesizes from

carbon dioxide and ammonia. (Urea is the primary solid

component of urine, and it is eventually excreted by

the kidneys.) Essential trace elements such as iron

and copper as well as vitamins A, D, and B12 are also

stored in the liver.

 

The detoxifying function is an essential part of human

body metabolism, with the liver playing a key role in

the process. Toxic chemicals, of both internal and

external origin, constantly bombard the liver. Even

our normal everyday metabolic processes produce a wide

range of toxins that are neutralized in the liver.

 

The regenerating capacity of the liver is one of the

most intriguing survival mechanisms of the body. The

liver is an incredibly resilient organ. Up to 75% of

its cells can be surgically removed or destroyed by

disease before it ceases to function (AMA 1989). As

with some other organs, the liver has been designed

with an excess of tissue to protect it from damage or

loss of function. The healthy parts of the liver have

an amazing capacity to regenerate new, healthy liver

tissue to replace damaged liver tissue. We are very

fortunate that the liver has a regeneration capacity

because our health depends on a well-functioning

liver.

 

CONDITIONS LEADING TO LIVER DAMAGE

 

The symptoms that are indicative of reduced liver

function or possible liver damage include general

malaise; fatigue; digestive disturbances such as

constipation; allergies and chemical sensitivities;

weight loss; jaundice; edema; and mental confusion.

Generalized pruritus (itching), nausea, and vomiting

can also result from impaired hepatofunction. The

causes of liver damage are numerous and may include

congenital defects (malformed or absent bile ducts);

obstructed bile ducts (cholestasis); autoimmune

disorders; metabolic disorders (hemochromatosis,

Wilson's disease); tumors; toxins (drugs, overdoses,

poisons); alcohol-related conditions (cirrhosis);

bacterial and parasitic infections; and viral

infections (hepatitis B and C). This section discusses

several chronic disorders and diseases that can lead

to degenerative liver damage without proper diagnosis

and treatment.

 

Cholestasis

Cholestasis is interruption or stagnation of the bile

flow in any part of the biliary system, beginning with

the liver. Cholestasis has several causes, including

obstruction of the bile ducts by the presence of

gallstones or a tumor, drug and alcohol use,

hepatitis, and existing liver disease (Glanze 1996).

In the United States, an important cause of

cholestasis and impaired liver function is the

consumption of alcohol. Other common causes of

cholestasis are viral hepatitis and the side effects

of various drugs, particularly steroidal hormones

(including estrogen and oral contraceptives).

 

Cholestasis can cause alterations of liver function

tests, indicating cellular damage. In the initial

stages of liver dysfunction, standard tests (serum

bilirubin, alkaline phosphatase, SGOT, LDH, GGTP,

etc.) may not be sensitive enough to be of value for

complete, early diagnosis. However, the measurement of

serum bile acids is a safe, sensitive test to

determine the functional capacity of the liver.

Treatment for cholestasis includes surgery so that

there will be unobstructed bile flow from the liver.

Drug-induced cholestasis will generally disappear if

the causative drug is discontinued. There is no

specific treatment for cholestasis caused by

hepatitis. However, bile flow will improve slowly if

inflammation of the liver can be resolved.

 

Wilson's Disease

Wilson's disease is an inherited disorder

characterized by the liver's inability to metabolize

copper, resulting in the accumulation of excessive

amounts of copper in the brain, liver, kidney, cornea,

and other tissues. The resulting copper accumulation

and toxicity result in liver disease and cause brain

damage in some patients. Although deposits of copper

begin at birth, it may be some time until the symptoms

of liver disease become evident. Patients, generally

between the ages of 10-40, present symptoms of liver

disease; a movement disorder associated with

neurological disease; behavioral abnormalities; or

often a combination of these. Blood testing will

reveal elevated liver enzymes. Symptoms of hepatitis

and cirrhosis may be evident. Secondary injury from

the accumulation of copper in the body may include

kidney damage, neurological disorders, hemolytic

anemia, and osteoporosis.

 

Copper also accumulates in other body organs,

particularly the brain, and may result in difficulty

with speech, trembling, writing problems, unsteady

gait, depression, suicidal impulses, and loss of

mental functions. The other body organs may also be

damaged by copper overload. Copper can accumulate in

the cornea of the eye and cause a characteristic brown

pigmentation called Kayser-Fleischer rings. Hemolytic

anemia, a low blood count related to damage of red

blood cells, may occur in patients with Wilson's

disease. There may also be injury to the kidneys from

copper overload. Finally, severe bone disease from

osteoporosis can occur in patients with Wilson's

disease.

 

If Wilson's disease is left untreated, increasing

damage to body organs will occur, especially in the

liver and brain. D-penicillamine is a copper chelating

agent that is administered to remove excess copper and

prevent further accumulations. Trientine may also be

used as a copper chelating agent. Both drugs are

administered with vitamin B6 (see the Heavy Metal

Toxicity protocol for additional information on

chelation). Foods high in copper content such as

shellfish, nuts, chocolate, liver, and mushrooms must

be avoided.

 

Because Wilson's disease can be effectively treated,

it is extremely important for physicians to learn to

recognize and diagnose the disease. Treatment options

have evolved rapidly in the last few years, with zinc

now being an important choice in most situations

(Brewer et al. 1999). Brewer et al. (1999) consider

zinc to be so important in the treatment of Wilson's

disease that they refer to it as being " the drug of

choice. "

 

Wilson's disease requires management by a physician.

Self-treating this condition with zinc is not

recommended.

 

Autoimmune Hepatitis

Autoimmune hepatitis is associated with an increase in

circulating autoantibodies and gammaglobulin resulting

in progressive inflammation of the liver. The symptoms

of Type-I autoimmune hepatitis (the most common) are

characterized by the presence of antinuclear

antibodies and a resemblance to symptoms of systemic

lupus erythematosus. The disease occurs most commonly

in females during adolescence or early adulthood.

Other autoimmune disorders may be present with

autoimmune hepatitis including thyroiditis, ulcerative

colitis, vitiligo (loss of skin pigmentation), and

Sjogren's syndrome (characterized by dry mouth and

eyes).

 

Fatigue, abdominal discomfort, aching joints, itching,

jaundice, enlarged liver, and spider angiomas (blood

vessels) on the skin are the most common symptoms.

More severe complications of liver disease may occur

as the disease progresses.

 

Up to 80% of patients have long-term survival with

appropriate treatment. Prednisone and azathioprine are

usually administered to treat immunosuppression. The

goal of treatment is to control rather than cure the

disease.

 

Hepatitis B

In the United States and Europe, approximately 1.25

million people are chronically infected with the

hepatitis B virus (Malik et al. 2000). About 5-10% of

those with acute hepatitis B will develop chronic

infection. The remainder will recover and develop

antibodies to the virus that make them immune from

further viral activity (Lammert et al. 2000; Mayerat

et al. 1999). At least 1 million chronically infected

individuals die each year of complications due to

HBV-related diseases, especially liver cancer and

cirrhosis. In the entire world, about 5% of the

population or 350 million people have chronic

hepatitis B (Gumina et al. 2001).

 

Hepatitis B causes inflammation of the liver resulting

from infection with a DNA-type virus. The infection is

passed via blood products, as in transfusions or in

the sharing of contaminated needles. It may also be

acquired by exposure to body fluids in addition to

blood, during sexual intercourse, and in transmission

from mother to fetus. About 5-10% of volunteer blood

donors show evidence of having prior hepatitis

B--meaning that they once did have hepatitis B and may

or may not still be infectious with the viral agent.

 

The incidence of hepatitis B is increased in dialysis

patients, IV drug users, persons with AIDS, transplant

recipients, and patients frequently receiving blood

transfusions such as those with leukemia or lymphoma.

When acute hepatitis occurs, symptoms include

weakness, nausea, vomiting, body aches (myalgias),

diarrhea, fever, joint pains (arthralgias), jaundice

(yellow discoloration of the skin and whites of the

eyes), loss of appetite, weight loss, loss of interest

in tobacco products, and sometimes an itching skin

rash. The average duration of symptoms of acute

hepatitis B is 1-3 months. During the final phase of

symptoms, the body begins to build immunity against

the hepatitis B infection and does become immune 90%

of the time (Lammert et al. 2000). In the other 10%,

however, a state of persistent infection occurs for

more than 6 months. These persons are designated as

having chronic hepatitis B. A liver biopsy is done in

those patients having chronic hepatitis B and about

one-third of these have chronic active hepatitis and

two-thirds have chronic persistent hepatitis. Of these

two types, the chronic active hepatitis is more

aggressive and has a more rapidly progressing course.

 

Two forms of therapy are now licensed for use in

chronic hepatitis B infection: interferon-alpha and

lamivudine (Epivir). A vaccine for hepatitis B now

exists and is frequently given to newborns, overseas

travelers, and other people at risk to exposure (refer

to the Hepatitis B protocol for more information and

specific therapies).

 

Hepatitis C

Hepatitis C can be transmitted by blood and blood

product transfusion. Up to 170 million persons are

infected worldwide. In the United States, more than 4

million people are infected with HCV. Most liver

transplants in the United States are a result of

hepatitis C. Hepatitis C has a frightening tendency to

result in chronic hepatitis, resulting in cirrhosis

(15-20% of those infected) or hepatocellular carcinoma

(primary liver cancer) (Ou 2002).

 

The hepatitis C virus (HCV) is an RNA virus, spherical

and enveloped in a lipid (fatty) outer envelope, which

can be transmitted by narcotics use, transfusion of

blood products, and exposure of medical personnel to

infected patients. In some cases, the reason one

contracts hepatitis C cannot be determined. The

hepatitis C virus inflicts most of its damage by

latching onto molecules of iron and generating

free-radical damage to liver cells. These free

radicals can induce liver inflammation, cirrhosis, and

primary liver cancer via oxidative attacks on liver

cells.

 

Successful eradication of the hepatitis C virus from

the body often requires that iron levels in the liver

and blood be at very low levels. In many cases, high

stores of iron in the liver preclude successful

therapy against the hepatitis C virus. It is desirable

to reduce iron levels in the body before initiating

treatment with conventional (interferon and ribavirin)

therapy. Despite substantial scientific evidence, few

physicians implement iron-depletion therapy when

treating hepatitis C. This partially accounts for the

high failure rate to eradicate the virus.

 

In patients with hepatitis C, particularly those who

are HIV-positive, a systemic depletion of glutathione

is present, especially in the liver. This depletion

may be a factor underlying the resistance to

interferon therapy. This finding represents a

biological basis for taking supplements that boost

cellular glutathione levels. Glutathione is a critical

factor in protecting liver cells against free-radical

damage.

 

Standard therapy for hepatitis C has consisted of

ribavirin combined with interferon. However, a

combination therapy of peginterferon alpha-2b and

ribavarin is currently the standard of care (refer to

the Hepatitis C protocol for more information and

specific therapies).

 

Hemochromatosis

Hemochromatosis is a hereditary disorder in which too

much iron is absorbed from the diet resulting in

free-radical damage to the liver, heart, and pancreas.

It is estimated that over 1 million Americans suffer

from the disease. If diagnosed early, hemochromatosis

can be controlled by phlebotomy (giving blood) until

stored iron levels are reduced. High levels of

antioxidants and herbal detoxifiers are usually

recommended to neutralize free radicals generated by

excess iron. Chelation therapy is an alternative

treatment in which a synthetic amino acid is

administered intravenously to bind and extract

unwanted metals from the body. People with

hemochromatosis must avoid iron-fortified foods,

cast-iron cookware, and red meat. Symptoms may not

appear until middle age, after multiple organ damage

has occurred. Due to blood loss from menstruation and

pregnancy, the disease is less prevalent in women than

men (refer to the Hemochromatosis protocol for more

information and specific therapies).

 

Steatosis, Steatohepatitis, and Cirrhosis

Steatosis (or fatty liver) is a common finding in

biopsy of the human liver. Fatty liver is a condition

in which fat accumulates within the liver cells

(hepatocytes) without causing any specific symptoms.

(Fatty liver is defined as either more than 5% of

cells containing fat droplets or total lipid exceeding

5% of liver weight.)

 

Fatty liver is usually a long-standing chronic

condition, occurring in association with a wide range

of diseases--exposure to poisonous and toxic

substances, taking certain drugs, and drug abuse

(injecting recreational drugs) (Glanz 1996)--although

in clinical practice, the majority of cases are the

result of excessive use of alcohol, diabetes, and

obesity. Less common are occurrences of acute fatty

liver during pregnancy or as a response to the

administration of tetracyclines, acetaminophen,

prescription drugs, and toxins.

 

Our understanding of the fatty liver condition has

advanced considerably. At one time, fatty liver was

believed to be a benign, reversible condition.

However, clinical studies now demonstrate that fatty

liver, whether from alcoholic or nonalcoholic origin,

can lead to inflammation, cell death, and fibrosis

(steatohepatitis), perhaps even progression to

cirrhosis. Cirrhosis is the irreversible end result of

fibrous scarring, a response by the liver to a variety

of long-standing inflammatory, toxic, metabolic, and

congestive damage processes (refer to the Liver

Cirrhosis protocol for more information and specific

therapies).

 

As stated earlier, in the Western world, alcohol is a

common cause of fatty liver and is the second most

common cause of cirrhosis. However, there are

considerable inter-individual differences in the

degree of liver damage produced by excessive alcohol

intake. There seems to be no correlation between the

incidence and severity of fatty liver and either the

amount, type, or duration of alcohol abuse. In some

individuals, it is unclear why fatty liver, whatever

its etiology, never progresses to steatohepatitis and

cirrhosis.

 

Obesity is among the causes for nonalcoholic

steatohepatitis (NASH) and is considered to be the

most common cause. There is evidence to suggest that

liver disease can actually be considered to be a

complication of obesity. However, no major prospective

longitudinal studies of NASH have been carried out.

Generally, it seems that the risk of progression to

cirrhosis is low for nonobese individuals, but

significant among obese individuals. Unfortunately,

there is also no predictable correlation between

symptoms (or lack of them), abnormality of liver

function tests, and severity of liver tissue damage.

 

As early as 1985, a study of 50 unselected, obese

subjects who were admitted to a hospital for weight

reduction found that 10% had normal livers, 48% had

fatty livers, 26% had steatohepatitis, 8% had

fibrosis, and 8% had cirrhosis (Braillon et al. 1985).

Obesity was defined as being 21-130% above ideal body

weight.

 

Interestingly, among patients with fatty liver related

to obesity, it has been observed that rapid weight

loss caused by dieting and intestinal bypass surgery

actually increased the risk for developing

steatohepatitis. The resulting increase in the

concentration of fatty acids and/or ketones within the

liver severely augmented the generation of free

radicals (Day et al. 1994).

 

A study by Yang et al. (1997) indicated that obesity

also increases susceptibility to endotoxin-mediated

liver injury. Endotoxins are cell wall components

produced by intestinal Gram-negative bacteria that are

thought to play a role in liver injury induced by

alcohol and other hepatotoxins. Under normal

conditions, endotoxins are absorbed into the portal

venous circulation and detoxified by the liver.

Hepatic dysfunction interferes with this clearing

mechanism and amplifies the negative activities of

endotoxin, such as lipid peroxidation, reduced P-450

function, and impairment of the immune system.

 

Berson et al. (1998) summarized well insights from

research on the mechanisms of steatohepatitis:

 

* Its development requires a double hit, the first

producing steatosis, the second a source of oxidative

stress capable of initiating significant lipid

peroxidation. This concept provides a rationale for

both the treatment and prevention of disease

progression in steatosis of alcoholic and

non-alcoholic causes. Management strategies should

ideally be directed at reducing the severity of

steatosis and at avoiding and removing the triggers of

inflammation and fibrosis. Specific treatment

modalities for at-risk individuals might include

sensible weight reduction, cessation of exposure to

toxins and treatment with antioxidants and inhibitors

of peroxisomal

b-oxidation.

 

Toxic Damage to the Liver

It is the external environment that contributes most

to the load of toxins that the liver has to detoxify.

Today, the burden on the liver is heavier than ever

before in history. Additionally, nutritional

deficiencies and imbalances from unhealthy eating

habits add to the production of toxins, as do alcohol

and many prescription drugs, further increasing stress

on the liver and requiring a strong detoxification

capacity. Surprisingly, even unprocessed organic foods

can have naturally occurring toxic components that

require an effective detoxification system.

 

Toxic chemicals are found in the food we eat, in the

water we drink, and in the air we breathe, both

outdoors and indoors. In a study by the Environmental

Protection Agency (EPA), chemicals such as p-xylene,

tetrachloroethylene, ethylbenzene, and benzene were

documented as " everywhere present " in the air (Wallace

et al. 1989). Listed as " often present " were

chloroform, carbon tetrachloride, styrene, and

p-dichlorobenzene. A customary trip to a gas station

or a dry cleaner (as well as smoking) results in

elevated levels of inhaled toxins.

 

The Food and Drug Administration (FDA) has found an

alarming level of chlorinated pesticides in food.

Dichlorodiphenyldichloroethylene (DDE) was found in

63% or more of 42 food samples, even though the use of

dichlorodiphenyltrichloroethane (DDT) and DDE has been

banned in the United States since 1972. DDE is a

breakdown product of DDT. Unfortunately, carried by

the winds, toxic chemicals used anywhere in the world

can move easily around the globe. There is enough

evidence of a connection between chemical exposure and

chronic health problems for us to be aware that

herbicides, pesticides, household chemicals, food

additives, etc. pose serious health concerns.

 

So what happens when the liver's detoxification system

is overloaded? The answer is simple. When the liver

does not function properly, toxins that we are exposed

to accumulate in the body. These toxins affect us in

numerous ways, and have damaging effects on many body

functions, particularly the immune system, causing

chronic health problems. It is not surprising that an

overburdened and undernourished liver can be a root

cause of many chronic diseases.

 

Cancers are also thought to be a result of the effects

of environmental carcinogens (e.g., cigarette smoke,

chemical fumes, toxic exhaust, and airborne

particulates), particularly if combined with

deficiencies of nutrients required for optimal

functioning of the detoxification and immune systems.

In a study of chemical plant workers in Turin, Italy,

Vineis et al. (1985) analyzed the association of

bladder cancer according to occupation (i.e.,

textiles, leather, printing, dyestuffs, tire and

rubber goods production). Highest risks were for the

leather, dyestuffs, and tire production industries. An

association was found for cancer and the aromatic

amines, with the risk being estimated at 10% for those

occupations consistently associated with bladder

cancer. Vineis et al. (1984) also found that there was

a multiplicative effect of relative risks for persons

in high-risk occupations who also smoked cigarettes.

 

How the Liver DetoxifiES

 

The liver has three main detoxification pathways:

 

* Filtering the blood to remove large toxins.

* Enzymatically breaking down unwanted chemicals.

This usually occurs in two steps, with Phase I

modifying the chemicals to make them an easier target

for the Phase II enzyme systems.

* Synthesizing and secreting bile for excretion of

fat-soluble toxins and cholesterol.

 

Filtering the blood is an essential detoxifying

function of the liver. As noted earlier, our total

blood supply passes through the liver several times a

day and at any given time, about a pint of blood is in

the liver undergoing detoxification. Blood

detoxification is critical because the blood is loaded

with bacteria, endotoxins, antigen-antibody complexes,

and other toxic substances from the intestines. A

healthy liver clears almost 100% of bacteria and

toxins from the blood before the blood enters the

general circulation.

 

The second essential detoxifying role of the liver

involves a two-step enzymatic process for the

neutralization of unwanted chemical compounds, such as

drugs, pesticides, and enterotoxins from the

intestines. Even normal body compounds such as

hormones are eliminated in this way. Phase I enzymes

directly neutralize some of these chemicals, but many

others are converted to intermediate forms that are

then processed by Phase II enzymes. These intermediate

forms are often much more chemically active and

therefore more toxic than the original substances.

Therefore, if the Phase II detoxification system is

not working properly, the intermediates linger and

cause damage.

 

Phase I detoxification involves a group of 50-100

enzymes that has been named the cytochrome P450

system. These enzymes play a central role in the

detoxification of both exogenous (beginning outside

the body, such as drugs and pesticides) and endogenous

(coming from inside the body, such as hormones)

compounds and in the synthesis of steroid hormones and

bile acids.

 

A side effect of this metabolic activity is the

production of free radicals that are highly reactive

molecules that will bind to cellular components and

cause damage. The most important antioxidant for

neutralizing these free radicals is glutathione, which

is needed for Phase I and Phase II detoxification.

When exposure to high levels of toxin produces so many

free radicals from Phase I detoxification that

glutathione is depleted, Phase II processes that are

dependent on glutathione cease. This causes an

imbalance between Phase I and Phase II activity,

causing severe toxic reactions as a result of the

build-up of toxic intermediate forms.

 

Phase II detoxification involves conjugation, meaning

a protective compound becomes bound to a toxin.

Besides glutathione conjugation, the other pathways

are amino acid conjugation, methylation, sulfation,

sulfoxidation, acetylation, and glucuronidation. These

enzyme systems need nutrients and metabolic energy to

function. As noted earlier, if liver cells do not

function properly, Phase II detoxification slows down

and increases the toxic load of toxic intermediates.

 

The third essential detoxifying role of the liver is

synthesis and secretion of bile. The liver

manufactures approximately a quart of bile every day.

Bile serves as a carrier to effectively eliminate

toxic substances from the body. In addition, bile

emulsifies fats and fat-soluble vitamins in the

intestine, improving their absorption. When the

excretion of bile is inhibited (cholestasis), toxins

stay in the liver longer and subject the liver to

damage.

 

Free-Radical Damage and Lipid PeroxidatiON

 

Oxidative damage from the production of free radicals

has far-reaching consequences in the body. Lipid

peroxidation is a term that describes fats that have

been chemically damaged by oxygen free radicals. Cell

membranes consist mainly of layers of phospholipids.

As free radicals attack the cell membrane, injury and

eventual death to the cell occur due to DNA strand

breakage. DNA is the cellular blueprint that is

required for replication. Oxidative stress also

affects circulating lipids in the body including

cholesterol, 80% of which is produced in the liver.

Peroxidized cholesterol has been shown to damage

arteries, leading to atherosclerosis, and a growing

body of evidence supports a role for lipid

peroxidation in the continued development of liver

damage.

 

While cell damage in the human liver is likely

multifactorial, free radicals have been implicated in

a variety of liver diseases, particularly in the

presence of iron overload, ethanol consumption, and

ischemia/reperfusion injury, either initiating or

perpetuating liver damage. Additionally, free

radical-initiated lipid peroxidation appears to play a

role in hepatic fibrogenesis (Britton et al. 1994).

The role of free radicals is significant in toxic

liver injury that is often induced by drugs and

chemicals. Damage is first caused by the toxin itself

and then is continued when the toxin is metabolized by

the liver (Feher et al. 1992).

 

TREATMENT OF DEGENERATIVE LIVER CONDITIONS

 

Conventional Medical Therapy

Unfortunately, liver damage caused by degenerative

conditions is irreversible. There are no commonly

accepted, effective, conventional drug therapy regimes

to prevent or reverse liver damage. Treatment

primarily consists of identifying the underlying

causes of disease, determining possible steps to slow

or stop progression of degeneration, and managing

symptoms. One causal factor is alcohol: stopping the

intake of alcohol will help stop progression. Ending

the use of hepatoxic drugs and removing sources of

environmental toxins will also stop progression. The

possible presence of metabolic diseases

(hemochromatosis, Wilson's disease) should be

investigated. Identifying the presence of hepatitis

viruses is essential. Because obesity plays an

important role in fatty liver, attention to weight

control is essential.

 

Itching is a very troublesome symptom for patients

with liver disease. It is also a very difficult

symptom to manage for physicians. The reason why

patients with liver disease itch is not understood.

One thought is that certain substances accumulate in

the blood as a result of liver disease and cause

itching. The nature of these substances is under

investigation, but some evidence suggests that normal

substances found in blood plasma (e.g., endogenous

opioids known as enkaphalins) for some unknown reason

cause itching in liver disease patients.

Itching/scratching studies have also shown that some

patients manifest scratching in a 24-hour rhythm

(circadian), suggesting that neurotransmitters in the

brain may cause itching (Bergasa 2002). At this time,

little treatment is available for itching secondary to

liver disease:

 

Natural Therapies

Scientific literature reports the results of research

using natural or alternative treatments for liver

conditions. Note that the vast majority of natural or

alternative treatments act by having an antioxidant

effect. As with almost all disease processes, research

has demonstrated that good antioxidant levels are

necessary for optimum health and to protect us from

the physical assaults of trauma and disease. Some of

the therapies listed in the following section also act

by having an effect on the immune system (an

immune-modulating effect). Other therapies have

anti-inflammatory benefits. Additionally, some agents

act by having both antioxidant mechanisms and immune

modulating mechanisms.

 

For the liver to continue to perform essential

functions, even when damaged, a healthy intake of

vitamins, minerals, and essential trace elements from

dietary sources such as fruits and vegetables is

important. However, few people can consistently

include enough fruits and vegetables in their daily

diets to protect them from degenerative conditions,

especially those related to age-related diseases;

toxic agents; carcinogens; inflammatory agents;

free-radical damage; and immune suppression. As an

adjunct to maintaining a healthy diet, supplements

can:

 

1. Maintain healthy metabolic functioning

2. Neutralize free-radical damage

3. Increase levels of glutathione, the liver's

natural antioxidant

4. Detoxify the liver

 

Supplements that Maintain Metabolic Health

Vitamin B complex. The vitamin B complex is a group of

vitamins (B1, thiamine; B2, riboflavin; B3, niacin;

B5, pantothenic acid; B6, pyridoxine; and B12,

cyanocobalamin) that differ from each other in

structure and the effect they have on the human body.

The B vitamins play a vital role in numerous essential

activities including enzyme activities (thiamine,

riboflavin, niacin, pantothenic acid, pyridoxine).

These enzyme activities also have many roles and are

involved in the metabolism of carbohydrates and fats;

functioning of the nervous and digestive systems; and

production of red blood cells. The B vitamins have a

synergistic effect with each other (AMA 1989). They

are found in large quantities in the human liver as

well as in many foods and yeast.

 

Folic acid. Folic acid is an important member of the

B-complex family, important for reducing harmful

levels of homocysteine, a sulfur-containing amino

acid, known to be a major culprit in heart disease.

The liver uses folic acid to facilitate healthy

methylation patterns that are essential components of

enzymatic detoxification. Decreased folate (folic

acid) is also associated with increased levels of

lipoperoxidases, that is, an indicator of increased

oxidative stress. Therefore, folic acid is potentially

beneficial if there is ongoing oxidative damage (Chern

et al. 2001).

 

Choline. Another of the B complex vitamins is choline,

essential for the use of fats in the body. It

comprises a large part of acetylcholine (a nerve

signal carrier). Choline also stops fats from being

deposited in the liver and helps move fats into the

cells. Deficiency of choline can lead to degenerative

diseases such as cirrhosis with associated conditions

such as bleeding, kidney damage, hypertension (high

blood pressure), cholesterolemia (high blood levels of

cholesterol), atherosclerosis (cholesterol deposits in

blood vessels), and arteriosclerosis (hardening of the

arteries) (Glanze 1996).

 

Acetyl-L-carnitine. Acetyl-L-carnitine has been shown

to convert some hepatic parameters to more youthful

levels. Acetyl-L-carnitine is the biologically active

form of the amino acid L-carnitine that has been shown

to protect cells throughout the body from age-related

degeneration. By facilitating the youthful transport

of fatty acids into the cell mitochondria,

acetyl-L-carnitine facilitates conversion of dietary

fats to energy and muscle. Acetyl-L-carnitine has also

been shown to regenerate nerves (Fernandez et al.

1997), to provide protection against glutamate and

ammonia induced toxicity to the brain (Rao et al.

1999), and to reverse the effects of heart aging in

animals (Paradies et al. 1999).

 

Antioxidants that Reduce Free-Radical Damage

Vitamin C. Vitamin C is a potent antioxidant that is

found naturally in many fruits and vegetables.

According to Garg et al. (2000), vitamin C has

protective effects against liver oxidative damage,

particularly when used in combination with vitamin E.

Researchers have found inadequate levels of vitamin C

in patients with degenerative diseases. Garg et al.

(2000) found that supplementation in rats lowered

plasma and liver lipid peroxidation, normalized plasma

vitamin C levels, and raised vitamin E above normal

levels.

 

Vitamin E. Vitamin E protects the lipid membrane from

oxidative damage. Adequate levels of vitamin E also

protect cholesterol from oxidative damage. Oxidized

cholesterol damages arteries and contributes to

atherosclerosis (Mydlik et al. 2002). Hepatocytes

incorporate vitamin E into lipoproteins, which then

transport it to various tissues in the body.

 

Coenzyme Q10 (CoQ10). CoQ10 is an antioxidant that is

protective for a liver that has been damaged by

ischemia (reduced blood flow) (Genova et al. 1999).

CoQ10 is also an important component of healthy

metabolism. It protects the mitochondria and cell

membrane from oxidative damage and helps generate ATP,

the energy source for cells. CoQ10 is absorbed by the

lymphatic system and distributed throughout the body.

Japanese researchers studied the effects of the toxic

drug hydrazine on liver cells. Hydrazine caused

remarkable increases in intracellular levels of

reactive oxygen species in hepatocytes, which were

suppressed by CoQ10 (Teranishi et al. 1999).

 

N-acetyl-cysteine (NAC). N-acetyl-cysteine is an amino

acid that acts as an antioxidant or free-radical

scavenger. Most scientific articles related to liver

protection with NAC emphasize this effect. NAC is

frequently used in medical settings to treat liver

toxicity associated with ingesting Tylenol (also

poisonous mushrooms) (Hazai et al. 2001; Attri et al.

2001).

 

Alpha-lipoic acid (ALA). Alpha-lipoic acid is an

antioxidant that has been shown to decrease the amount

of hepatic fibrosis associated with liver injury. Both

of these mechanisms suggest it has promise for

cirrhosis. Because alpha-lipoic acid is fat soluble,

it can penetrate the cell membrane to exert

therapeutic action. It has been shown to effectively

scavenge harmful free radicals, chelate toxic heavy

metals, and help to prevent mutated gene expression

(Biewenga et al. 1997). Another of its most beneficial

functions is to enhance the effects of other essential

antioxidants including glutathione, which is vital to

the health of the liver (Lykkesfeld 1998; Khanna et

al. 1999).

 

Selenium. Selenium is a trace element that acts by

several mechanisms, including detoxifying liver

enzymes, exerting anti-inflammatory effects, and

providing antioxidant defense. The presence of

selenium helps induce and maintain the glutathione

antioxidant system (Sakaguchi 2000).

 

Zinc. Zinc is an essential dietary nutrient and is

used in numerous drugs and preparations that are

protective. Zinc helps remove copper from the body and

is used as an adjuvant treatment in Wilson's disease

(Brewer et al. 1999).

 

Protecting and Improving Liver Function

S-adenosylmethionine (SAMe). SAMe is a methylation

agent (a methyl group donor) and is necessary for the

synthesis of glutathione. Medical studies have shown

that SAMe has beneficial antioxidant effects on the

liver and other tissues, particularly in protecting

and restoring liver cell function destroyed by the

hepatitis C virus. SAMe decreases the production of

liver collagen, which leads to the formation of

fibrous tissue (Deulofeu et al. 2000). SAMe is found

naturally in every cell of the body. It is synthesized

from a combination of the amino acid L-methionine,

folic acid, vitamin B12, and trimethylglycine,

provided all these ingredients are present and

performing (Anon. 2002).

 

Phosphatidylcholine (PC). Phosphatidylcholine is a

type of fat that is part of cell membranes. PC is one

of the most important substances for liver protection

and health and is a primary constituent of cell

membranes. PC acts by several mechanisms: exerting

potent antioxidant effects; inhibiting the tendency of

stellate cells to progress to cirrhosis; decreasing

apoptotic death of liver cells and thereby prolonging

the life of liver cells; stabilizing the cell

membrane, thus improving the integrity and function of

the liver cell; and exerting an antifibrotic effect

related to the breakdown of collagen (not only slowing

the progression of fibrosis, but also encouraging

regression of existing fibrosis) (Ma 1996; Lieber

1999; Pniachik 1999; Wolf 2001). A special form of PC

called polyenylphosphatidylcholine has been shown to

prevent the early changes in the damaged liver from

occurring before the actual development of cirrhosis

(Navender 1997).

 

Silymarin. Silymarin, (also known as milk thistle or

Silybum marinum) is a member of the aster family

(Asteraceae). The active extract of milk thistle is

silymarin (Bosisio et al. 1992), a mixture of

flavolignans, including silydianin, silychristine, and

silybin, with silybin being the most biologically

active. Silymarin has proven to be one of the most

potent liver-protecting substances known. Its main

routes of protection appear to be the prevention of

free-radical damage, stabilization of plasma

membranes, and stimulation of new liver cell

production. It has also been shown to inhibit lipid

peroxidation and to prevent glutathione depletion

induced by alcohol and other liver toxins, even

increasing total glutathione levels in the liver by

35% over controls (Valenzuela et al. 1989). Early

studies show that silymarin has the ability to

stimulate protein synthesis, resulting in production

of new liver cells to replace older, damaged ones

(Sonnenbichler et al. 1986a; 1986b). Studies also

demonstrate the benefits of silymarin for protection

from numerous toxic chemicals.

 

Branched-chain amino acids. Branched-chain amino acids

(leucine, isoleucine, and valine) are considered to be

essential amino acids because humans cannot survive

unless these amino acids are present in the diet.

Branched chain amino acids (BCAAs) are needed for the

maintenance of muscle tissue and appear to preserve

muscle stores of glycogen (stored form of

carbohydrates that can be converted into energy).

Dietary sources of BCAAs are dairy products and red

meat. Whey protein and egg protein supplements are

other sources. Most diets provide the daily

requirement of BCAAs for healthy people. However, in

cases of physical stress, we have increased energy

requirements, in particular persons with cirrhosis.

Studies on alcoholic cirrhosis patients have shown

benefits from supplementing valine, leucine, and

isoleucine. These branched-chain amino acids can

enhance protein synthesis in liver and muscle cells,

help restore liver function, and prevent chronic

encephalopathy (Shimazu 1990; Chalasani et al. 1996)

In studies, BCAAs have also been shown to have

therapeutic value in adults with cirrhosis of the

liver. According to the researchers, BCAAs seem to be

the preferred substrate to meet this requirement (Kato

et al. 1998).

 

SUMMARY

 

If you already have a degenerative liver condition, or

have symptoms of liver disease, consult a qualified

physician who is experienced in treating liver disease

and who will coordinate your treatment.

Supplementation with antioxidants, branched-chain

amino acids, and all of the B complex of vitamins

except B3 (niacin) has been shown to have protective

qualities and to be beneficial for the liver. The

following are important in preventing liver disease

and for providing beneficial supportive effects.

 

1. The B vitamins are essential for healthy

metabolic functioning. Working individually and

synergistically, they facilitate energy release and

the manufacture of new cells.

* B1 (thiamine), 500 mg

* B2 (riboflavin), 75 mg

* B5 (pantothenic acid), 1500 mg

* B6 (pyridoxine), 200 mg

* B12 (cobalamin), sublingual

methylcobalamin is recommended for better absorption,

one 5-mg lozenge 1-5 times daily

* Folic acid, 800 mcg daily

* Vitamin B3 (niacin) should be avoided by

people with liver conditions as it disrupts healthy

methylation patterns.

2. Choline helps reduce the amount of fat deposited

in the liver, 1500 mg daily.

3. Acetyl-L-carnitine will help to maintain

mitochondrial health, take 2 daily doses of 1000 mg.

4. Antioxidants will protect the liver from the

damaging effects of free radicals produced from

environmental toxins.

* Take at least 2500 mg of vitamin C daily.

* Vitamin E (400 IU of D-alpha tocopheryl

succinate and 200 mg of gamma tocopherol daily provide

broad-spectrum antioxidant protection).

* CoQ10 protects the mitochondria from

oxidative damage and provides cellular energy, 100-300

mg daily.

* N-acetyl-cysteine (NAC) enhances the

production of glutathione and has protective benefits

for the liver from toxins. Take 600 mg daily.

* Alpha-lipoic acid can dramatically

increase glutathione levels inside of cells. Suggested

dose is 250 mg 2-3 times a day.

* The trace mineral selenium has shown

antioxidant protection in the liver. Zinc is often

deficient in the cirrhotic liver and acts as a

chelator in removing copper from the system. Take

selenium, 200 mcg daily, and zinc, 30-85 mg daily.

5. Several supplements can benefit a damaged or

diseased liver:

* S-adenosylmethionine (SAMe) is needed to

synthesize glutathione and has restored liver function

from damage due to hepatitis C. The suggested dose of

SAMe is 400 mg 3 times daily. Do not take SAMe on an

empty stomach.

* Polyenylphosphatidylcholine (PPC) has been

shown to prevent the development of fibrosis and

cirrhosis and to prevent lipid peroxidation and

associated liver damage from alcohol consumption. PPC

is sold as a drug in Europe. A product called

GastroPro is one of the few American dietary

supplements to provide pharmaceutical-grade

polyenylphosphatidylcholine. Take two to three 900-mg

capsules daily.

* Silymarin extract from milk thistle can

raise glutathione levels and has shown multi-faceted

protective benefits to the liver. The most active

flavonoid in silymarin is silibinin. A product called

Silibinin Plus is formulated to provide the same

silibinin extract used in European prescription drugs.

One 325-mg capsule taken twice daily is recommended

for healthy people. Patients with liver disease may

take up to 6 capsules daily.

* Branched-chain amino acids can enhance

protein synthesis in the liver and are particularly

beneficial in alcoholic cirrhosis. The suggested dose

is 2-4 capsules daily between meals with fruit juice

or before eating. Each capsule should contain 300 mg

of leucine, 150 mg of isoleucine, and 150 mg of

valine.

 

For more informatiON

 

More information on conventional therapies is

available by contacting the American Liver Foundation,

(800) 223-0179.

 

Product availabiliTY

 

GastroPro (polyenylphosphatidylcholine), Silibinin

Plus, branched-chain amino acids, choline capsules, B

vitamins, SAMe, vitamin C, vitamin E (tocopheryl

succinate and gamma tocopherol), selenium, zinc,

coenzyme Q10, acetyl-L-carnitine, alpha-lipoic acid,

and N-acetyl-cysteine (NAC) may be ordered by calling

(800) 544-4440 or by ordering online.

 

 

 

Disclaimer

 

This information (and any accompanying printed

material) is not intended to replace the attention or

advice of a physician or other health care

professional. Anyone who wishes to embark on any

dietary, drug, exercise, or other lifestyle change

intended to prevent or treat a specific disease or

condition should first consult with and seek clearance

from a qualified health care professional.