Chanchal Cabrera MSc, MNIMH, AHG | Medicinal Herbalist

The liver
Orally ingested substances are taken up by the hepatic portal vein that drains the blood from the stomach and intestines (except the long chain fatty acids which are taken up by the lymphatics). Substances delivered from the gut to the liver are subject to the ‘first pass effect’ whereby hepatic activity may alter or degrade the ingested substance before it ever reaches the systemic circulation for delivery to the tissues. The liver is the largest organ of the body, weighing in at as much as 2.5 lbs in an adult. It acts as a sort of giant selective sponge, assessing everything it encounters and either using it to make something else, storing it or eliminating it. Proper liver function is critical to good health and the liver has an impressive ability to rejuvenate and renew itself. However, chronic abuse can overwhelm the system and result in declining health. Conditions such as arthritis, rheumatism, eczema, psoriasis, impaired immune function and cancer have been linked to chronic hepatic dysfunction.

Functions of the liver
Protein metabolism
Carbohydrate metabolism
Fat metabolism
Vitamin storage
Immune function
Detoxification

Protein metabolism
The liver breaks down unwanted amino acids into ammonia then carries out the urea cycle to remove the ammonia which is toxic. It carries out inter-conversion among the amino acids and builds proteins. The liver forms the 3 plasma proteins:
Albumin - responsible for the transport of fatty acids, bilirubin, drugs and hormones in the blood and for the maintenance of the osmotic pressure of blood;
Globulin - involved with the transport of fats as lipoproteins and the transport of iron;
Fibrinogen - involved with the formation of blood clots and of the fibrin net that limits the spread of infection.

Carbohydrate metabolism
When blood levels of sugar are high, under the influence of Insulin, the liver makes glycogen from glucose (glycogenesis) and stores this glycogen against times of low blood sugar. In hypoglycemia, under the influence of Glucagon, the liver manufactures glucose from stored glycogen as well as from amino acids, fats, proteins and other sugars (gluconeogenesis).

Fat metabolism
The liver is the major site of fat metabolism in the body. It carries out oxidation (breakdown) of fatty acids, the formation of lipoproteins for the transport of fats in the blood stream, the formation of cholesterol and the breakdown of excess cholesterol into the bile salts, the formation of phospholipids and the conversion of excess carbohydrate and amino acids to fat for storage.

LIPOPROTEINS IN THE BODY

	Chylomicron	VLDL	LDL	HDL
Site of synthesis	Intestinal mucosa	Liver	Liver	Liver & intestine
Composition (%)
Triglycerides Cholesterol Phospholipids Protein	90 5 4 1	65 13 12 10	10 43 22 25	2 18 30 50
Function	Transport of absorbed dietary fats.	Transport of trii-glycerides from liver	Transport of choles- terol to peripheral tissues	Transport of choles terol and phospho- lipids to liver.

Immune function
The liver contains specialized macrophages called Kupffer cells that remove many harmful viruses, bacteria, yeast toxins and other unwanted substances from the blood. The Kupffer cells are phagocytic, engulfing and ‘digesting’ unwanted substances and thus contributing to the blood purifying or cleansing activity of the liver.

Vitamin Storage
The liver is the storage site for vitamins A, B12 and D, as well as iron.

Detoxification and elimination
The liver is constantly engaged in disassembly, alteration and reconstruction of molecules, both those manufactured by metabolic processes and those taken in from the external environment. Substances taken into the body are altered in various ways in the liver to form other substances for use, elimination or storage. The eliminative processes carried out by the liver are a means of making substances more water soluble and therefore easier to excrete, usually via the bile or the kidneys. The metabolites of a substance may be pharmacologically inert or may have effects on the body that may even exceed those of the original substance. Some drugs, indeed, only become active after passing through the liver and being chemically altered by it.

Hormones, drugs, artificial chemicals, alcohol and tobacco are all broken down and detoxified by the liver. The detoxification functions of the liver, though, evolved to deal with metabolic waste products and naturally occurring toxins, often in small amounts. It struggles today to keep pace with all the artificial substances thrown at it. Modern man eats around 3 lbs of artificial chemicals annually, comprising around 3000 different items. All of these must be processed by the liver. If the metabolic pathways required are already in use or if pathways don’t exist, then toxins are stored in fat tissue.

1) oxidation, reduction or hydrolysis which provides reactive groups that are then available for

2) conjugation or the binding of the remedy with a second substance, rendering it more water-soluble.

Phase 1 (non - synthetic reactions)
Oxidation, reduction or hydrolysis of a substance provides an hydroxyl (OH), a carboxyl (COOH) or an (NH₂ ) group which permits further metabolism. These non - synthetic reactions are catalyzed by enzymes from the endoplasmic reticulum in the liver cells. Most of these enzymes are relatively non - specific which means that often the liver can metabolize substances which do not naturally occur in the body. The enzymes are collectively called the Cytochrome P450 series. Phase one reactions change non-polar (non-water soluble) substances into moderately or slightly water soluble forms. Cytochrome P450 is also found in other tissues including the brain, intestines, heart, adrenal cortex, testes, skin and spleen. This indicates that it is not only the liver which is capable of detoxifying noxious substances and metabolic wastes, but that many or most tissues can do it to some degree.

Phase 2 (synthetic reactions)
This involves the formation of new compounds by the conjugation of the OH, COOH or NH₂ group with other naturally occurring body substances in the liver. Conjugation renders the drug metabolically inactive and aids its excretion by making it more ionic (ie. more polar or water soluble). Conjugation with glutathione accounts for about 60% of phase 2 reactions. This amino acid is manufactured in the liver and also circulates in the blood stream where it is a powerful anti-oxidant. Conjugation with sulphur is responsible for removal of neurotransmitters, steroid hormones, bacteria, many drugs and industrial chemicals and the catecholamines (adrenalin / epinephrine). Deficiency of sulphur in the diet may contribute to the formation of Parkinson’s disease, Alzheimer’s disease, motor neurone disease, autism, rheumatoid arthritis and food or environmental sensitivities ^[i]. Conjugation with the amino acids taurine, glutamine, ornithine, arginine and especially glycine is responsible for the elimination of a great many drugs, toxins and fatty acids. Aspirin and canned soft drinks deplete glycine and inhibit this elimination pathway. Three other key pathways in phase 2 detoxification are glucuronidation, acetylation and methylation. Many drugs, environmental toxins, vitamins, neurotransmitters amino acids and hormones are processed through these pathways.

Enzyme induction
This is the enhancement of liver enzyme activity such that the rate of substance metabolism is increased. If enzyme induction is prolonged it may lead to a rise in liver weight, an increase in hepatic blood supply and a proliferation of the hepatic endoplasmic reticulum where Phase I enzymes are made and stored. Many substances may cause enzyme induction e.g. ethanol (alcohol), tobacco, herbicides & pesticides, food additives, food dyes and several drugs such as Griseofulvin, Chloral hydrate, Phenylbutazone & Meprobamate. The barbiturate tranquillizers have a major induction effect on enzyme activity and can shorten the active life of other drugs such as Digoxin and the cortico-steroids by 3 or 4 fold. It has even been suggested that tolerance to ethanol and the barbiturate tranquillizers may be partly due to an auto-induction of their own metabolizing enzymes. Dietary substances that may induce phase 1 reactions include charbroiled meats, citrus fruits, vitamins B1, B3 & C, foods in the cabbage family and high protein diets. A particular concern is that enzyme induction of phase I enzymes only, and not Phase II, can lead to an accumulation of intermediary metabolites, many of which may be more toxic than the parent molecule. Additionally, enzyme induction will shorten the useful life and reduce the availability of drugs, herbs or metabolites.

Enzyme inhibition
Possibly more significant than the induction of enzymes is their inhibition because this will prolong the active life of a drug or other toxic substance and so contribute to the ever present danger of having too much in the system (ie. overdosing). Some of the drugs that are known to block hepatic enzyme pathways include oral contraceptives, benzodiazepines, anti-histamines, and the mono amine oxidase inhibitors. Dietary substances known to inhibit phase 1 enzymes include grapefruit, turmeric, capsicum (chilli pepper) and cloves.

So far, very little research has been done into enzyme induction or inhibition by herbal agents, nor into the results of enzyme induction and inhibition on the effects of herbs in the body. Generally speaking, though, the chemical constituents of a herb are more compatible with the human body than are those which have been artificially isolated, extracted or synthesized. The constituents of a herb are made of the same basic building blocks as are our bodies and they are arranged in patterns that are very familiar to our bodies through hundreds of thousands of years of parallel evolution and regular exposure. It is generally assumed, therefore, that the issue of enzyme induction and inhibition is not so significant to the herbal practitioner. Recent research has suggested that Hypericum perforatum (St John’s Wort) may be a Phase I enzyme inhibitor and that this might be of clinical significance in concurrent use of the herb with certain drugs. So far, this research has been based on extremely small sample sizes so the significance of these findings is still controversial.

Systemic pathologies
Many disease processes may affect the rate of hepatic drug metabolism. A fever will generally increase the metabolic rate and shorten the time that a drug remains active in the system. Of particular concern to the practitioner are liver and kidney diseases. If the kidney function is impaired then there can be an accumulation of the conjugated remedy in the blood and tissues. The conjugation process is usually reversible so this situation can result in a higher than expected circulating level of active drug substance. In liver disease the effect on drug metabolism is perhaps less than could be expected because the liver has considerable 'spare capacity' (ie. by no means all the liver cells are actively involved in drug metabolism at any one time , although all have the same functional capacity). So liver diseases such as cirrhosis or jaundice have to be considerably advanced before there is a significant effect on drug metabolism.

Variations in age
In the foetus and the neonate the liver is immature and so cannot metabolize and excrete substances with total efficiency. Thus the plasma clearance rate is decreased and the effective life of the remedy is prolonged. A similar situation exists in the elderly where the levels of hepatic endoplasmic reticulum enzymes is diminished and so the effect of remedies is enhanced. It is therefore appropriate to give reduced doses of herbal remedies to children and the elderly, as well as possibly being useful to give remedies that support the liver.

Tests for liver function
Long before overt disease occurs, there may be subtle indications of impaired liver function. Sallowness of the skin, skin breakouts (pimples) or rashes and itching, dark circles under the eyes, gas, bloating and abdominal distention, nausea or abdominal discomfort from fatty foods, bad breath, constipation, unusually pale or unusually dark stools, headaches, a bitter taste in the mouth, yellow coating on the tongue, irritability, PMS, and joint stiffness or aching are all warning signs that toxins are not being adequately eliminated. Conventional tests of liver health such as liver enzymes are designed to identify pathology and do not give much indication of the functional ability of the liver or pre-pathology status. Private laboratories do offer functional testing but this is rarely covered by health insurance programs and many allopathic physicians are not familiar with them. Hair analysis and urine analysis can give important information about heavy metal accumulation. D-glucaric acid and mercaptic acid in the urine can give information about the patency of phase I and phase II reactions respectively. Oxidative stress tests using challenge substances such as caffeine and aspirin can provide much information about glutathione function. Urine testing for specific substance residue can indicate intestinal permeability. Comprehensive digestive stool analysis gives information about the digestive and absorptive ability, bacterial balance, yeast overgrowth, parasites and the immune functions of the intestinal cells. Organic acid testing can identify disturbances in the Krebs Cycle and hence disruptions in energy production. Amino acid, fatty acid, vitamin, mineral and hormone assays may also be helpful in assessing liver function and overall wellbeing.

Herbal formulas for liver health

Old Fashioned Blood Cleansing Compound Trifolium pratense (Red clover) 2 parts Urtica dioica (Stinging nettle) 2 parts Arctium lappa (Burdock) 1 part Zanthoxylum spp. (Prickly ash) 1 part Stillingia sylvatica (Queen’s delight) 1 part Echinacea spp. (Echinacea) 1 part Rheum palatum (Rhubarb) 1 part 1 tsp of the 1:3 tincture 3 x/day 4 heaping tsp of tea per cup water 3 x/day	Warming Digestive Stimulant Compound Rosmarinus officinalis (Rosemary) 1 part Mentha piperita (Peppermint) 1 part Melissa officinalis (Lemon balm) 1 part Erythrea centaurea (Centaury) 1 part Iris versicolor (Blue flag) 1 part Angelica archangelica (Angelica) 1 part Elletaria cardamom (Cardamom) 1 part Gentiana lutea (Yellow gentian) ½ part ½ tsp of the 1:3 tincture 3 x/day
Liver Cleansing Compound Taraxacum off. (Dandelion root) 1 part Taraxacum off. (Dandelion leaf) 1 part Silybum marianum (Milk thistle) 1 part Chionanthus virginicus (Fringe tree) 1 part Fumaria officinalis (Fumitory) 1 part Foeniculum vulgare (Fennel) 1 part 1 tsp of the 1:3 tincture 3 x/day 4 heaping tsp of tea per cup water 3 x/day	FiberFlow Stool Softening Compound Plantago ovata (Psyllium husk) 3 parts Ulmus fulvus (Slippery elm) 1 part Arctium lappa (Burdock) 1 part Althea off. (Marshmallow) 1 part Trigonella foenum-graecum (Fenugreek)1 part Foeniculum vulgare (Fennel) 1 part Oat bran 1 part Bentonite clay 1 part Take a heaping teaspoon to 1 tablespoon of the powder stirred into a glass of water on an empty stomach twice daily, followed by another glass of water
Laxative Compound Arctium lappa (Burdock) 2 parts Mentha piperita (Peppermint) 1 part Taraxacum off. (Dandelion root) 1 part Foeniculum vulgare (Fennel) 1 part Althea officinalis (Marshmallow) 1 part Zingiber officinalis (Ginger) 1 part Rheum palmatum (Rhubarb) 1 part Lobelia inflata (Lobelia) 1 part Two - three capsules twice daily	Spring Cleanse Tea Urtica dioica (Stinging nettle) 2 parts Arctium lappa (Burdock) 2 parts Galium aparine (Cleavers) 2 parts Stellaria media (Chickweed) 2 parts Trifolium pratense (Red clover) 1 part Taraxacum off. (Dandelion root) 1 part Taraxacum off. (Dandelion leaf) 1 part Mentha piperita (Peppermint) 1 part Foeniculum vulgare (Fennel) 1 part Glycyrrhiza glabra (Licorice) 1 part Berberis aquifolium (Oregon grape) 1 part 1 tsp of the 1:3 tincture 3 x/day 4 heaping tsp of tea per cup water 3 x/day