Inefficent Liver Function & Toxification



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Introduction
The Organs of Elimination
Liver Function
     Overview
     Phase 1 & 2 Enzymatic Function Summary
     Gluthatione and Methylation
     Glucuronic acid and Gilbert Syndrome
     Fructose Metabolism and Hereditary Fructose Intolerance
     Gallbladder Function
Herbs to Support the Liver, Kidneys and DIgestive Tract
     Liver and Gallbladder Support
     Kidney and Bladder Support
     Digestive Support
     General
Factors that may contribute to Inefficient Liver Functioning
Effects of Inefficient Liver Function
 

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Introduction:

Toxification is one of the most debated health issues of our time. Do we really build up a large number of harmful toxins over time such as pesticides, herbicides, preservatives, biotoxins, rogue fatty acids, heavy metals, PCBs and so on? Are the levels really that high and what effect do these chemicals have on our bodies? Do we really ingest all these things from air, food and water? Are our modern lifestyles and environments inherently detrimental to our health? Or are there other sources of heavy metal toxification such as mercury amalgam fillings or vaccinations?

It is frequently seen in CFS sufferers and as well sufferers of other conditions such as Autism, that elevated levels of toxins are present, and could very well be a significant factor in the condition itself. It is highly likely that high levels of toxicity in the body over decades is a major contributor to cancer. However, we are focussing here on how it relates to CFS and related conditions, and how removing the toxicity results can result in huge progress with patients.

The UK National Health Service (NHS) states that two of the causes of CFS and related conditions are 'thought' to be environmental pollution and neurotoxins. However it does not expand on this. Just where exactly do these toxins and pollutants come from? The implication is that CFS sufferers are the victims of freak toxic events, such as having a DDT shower, having a bath in liquid mercury, drinking liquid mercury or being in a nuclear explosion, and that the rest of the population are healthy and that their neurotoxin and pollution exposure is 'within acceptable tolerances'. However, CFS sufferers and those with related conditions are rarely to subjected to any more toxins and pollutants than anyone else. Clearly, some CFS sufferers experience slightly higher levels of toxicity than others on account on toxins excreted by elevated levels of bad bacteria, yeasts and parasites, and may be more sensitive to such contaminants in general than the rest of the population, and have many other complicating factors. But where does this leave the rest of the population? The vast majority of toxins built up in the body come from 'modern living' and affect everyone. It is likely Mr Average has an equivalent intake of toxins to sufferers of CFS (whose condition is often blamed on environmental pollution and neurotoxins). What it comes down to is how toxified 'Mr Average' is compared with someone who is suffering from CFS, and indeed why this should be. What is average or normal - how healthy does the majority of the population really want to be? Often people do not want to know about such issues until they are forced to acknowledge them through serious health problems, which is often the case with CFS sufferers.

It is a matter of debate as to why certain individuals build up more toxins in their bodies than others. Clearly in certain cases, the build up of toxins in certain individuals is a result of higher levels of exposure over prolonged periods (e.g. poor diet, drug abuse, mercury amalgam fillings, excessive numbers of vaccinations, polluted environments, etc.) and to a certain degree exposure from the mother whilst in the womb.

However, the degree to which an individual's body, tissues and cell membranes become over-toxified is often largely dependent on their liver function, its health and ability to cope with the steady stream of incoming toxins and to destroy/remove them, and also to cope with spikes of short term, high toxic input. Overload of the liver over long periods may decrease its overall effectiveness and lead to toxification of the body and decreased mitochondrial efficiency (which has a big knock on effect in terms of high level processes and functions in the body such as aerobic respiration and digestive function etc.) This is often a key reason why fatigue and other CFS symptoms appear.

Short term triggers that temporarily overload the liver may put excessive pressure on an already weak and burdened liver; as when anti-bodies and white blood cells attack these invaders, they must be destroyed and removed by the liver; the liver is thus rendered ineffective in removing and processing all the normal toxins in the body; toxins thus build up and affect mitochondrial function and other cellular processes in the body, as described above. This is why such infections are often triggers for CFS; and indeed why Post Viral Fatigue Syndrome occurs. 'Experts' often categorise both conditions as separate and unrelated.

Genetic factors may also be an influence in impaired liver function and the build up of toxins in the body, but these are only a small part of the story. Excessive electromagnetic pollution that is present in households, cars and in most modern environments from electronic and electrical devices and appliances and circuitry is another type of 'pollutant' or harmful external environmental factor that can exaccerbate chronic fatigue and ill health. This is of course not a physical chemical 'toxin', and is briefly discussed on the energetic therapies page. For some or all of these reasons, two people may have radically different levels of toxins in their blood and tissues, when they live in the same environment and have similar lifestyles.

We shall first examine the body's own methods of removing toxins from the body and the function of the liver in particular. We shall then explore what the effects of impaired liver function are and what the effects of toxins are in the body. We shall then examine what toxins are and where they come from. Finally, we shall then examine some cutting edge detoxification protocols. This is probably one of the most important pages on this web site. I cannot reiterate why it is important to really 'digest' the content on this page and understand it (at least on a high level).

After reading this page, please see also the Toxins and Detoxification pages as they are 3 parts of one larger article. Thank you.

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The Organs of Elimination:

The liver is the organ in the body that breaks down poisons present in the blood, such as alcohol, and removes toxic compounds such as biotoxins and heavy metals. The gallbladder then secretes into the digestive tract with its bile, for removal from the body in the faeces. Bile serves a number of functions, but helps to lubricate the digestive tract and acts as a medium to eliminate toxins from the liver. The liver and gallbladder have numerous other functions, including digestion, in the breakdown of fats.

The kidneys help to filter the blood, and will eliminate a lesser amount of such toxins and filter these off into the bladder for removal from the body in the urine (this is why it is important to drink sufficient water).

Fresh mineral water or ionised water is generally thought to be more efficient a medium for removing toxins from the body and tissues, as opposed to tap water, filtered water or even bottled mineral water. However, the liver and kidneys will only remove toxins that are present in the blood stream, and do not actively draw out toxins from our tissues. If toxins dissolve into our fatty tissues or for whatever reason end up attached to our inter- or intra-cellular membranes (e.g. mitochondrial membranes) in the tissues in the body (i.e. the body's lipids), then the liver will not be able to remove these toxins, unless they come loose through diffusion into the blood stream. This may or may not occur depending on the chemical bonds and electromagnetic attraction and the nature of their attachment/binding.

In addition to the liver and kidneys and their function in removing toxins into the faeces and urine respectively, there are other important mediums of detoxification. These are the skin, the mucus membranes and the lungs. One excretes a relatively tiny amount of such toxins in one's sweat, mucus and breath.

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Liver Function:

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Overview:

http://en.wikipedia.org/wiki/Liver

Quoted from a former article from ARL Pathology's Web Site (see the pdf below for the abbreviated version of this article including related diagrams that follow in the next section on this page) - My comments added in Square Brackets:

'The liver is metabolically most complex organ in the body and serves numerous vital functions. These include energy balance regulation, blood protein synthesis and immune modulation.

Efficient liver function is necessary for the processing and excretion of [Endogenous Toxic Chemicals] and [Exogenous Toxic Chemicals] (hormones, drugs, chemicals etc.) which are commonly referred to as 'xenobiotic' chemicals.

[Endogenous Toxins include the toxic end products of metabolism and also the toxins contained within bacteria but not normally excreted by the bacteria (endotoxins).]

[Exogenous Toxins include drugs (prescription, OTCs, recreational etc.), chemicals (agricultural, food additives, household and pollutants/contaminants) and also toxins excreted by bacteria and parasites (exotoxins).]

The liver possesses two mechanisms for the removal of unwanted chemicals from the body. In general these unwanted substances are lipophilic in nature and are therefore difficult to transport across cell membranes for excretion. The liver can chemically alter the compound by either an oxidation reaction (Phase I), or a conjugation reaction which adds a small molecule (Phase II).

These reactions have the effect of making the compound more polar or water soluble, thereby allowing it to be more easily excreted in the urine or bile. This biotransformation process occurs for a great number of xenobiotics such as enterotoxins (potentially toxic chemicals endogenously generated by gut bacteria), endobiotics (intermediate/end products of normal metabolism/enzymolysis etc), and exotoxins (ingested, inhaled and absorbed toxic chemicals).

Hepatic and cellular detoxification is basically the action of taking fat-soluble toxic materials and making them more polar or water-soluble in order to be excreted from the body. The process of biotransformation (i.e. detoxification) of drugs, xenobiotics (compounds entering the body from the outside environment) and endogenous substances which are produced within the body (e.g. stress hormones) are all carried out by the body's enzymatic detoxification pathways (Podolsky, et. al., 1994).

Phase I reactions are mixed function oxidase reactions (usually oxidation of toxic chemicals, but involving other types of reaction), which are managed, by a large family of enzymes called the Cytochrome P450 group.

Phase II reactions involve the addition of a small polar molecule to the chemical. This conjugation step may or may not be preceded by a Phase 1 reaction. The conjugation molecules are acted upon by specific enzymes to catalyse the reaction step. Molecules used by the liver for this purpose include glutathione, sulphate (e.g. sulphur from MSM, Cysteine, garlic), glycine, acetate (e.g. from NAC), L-Cysteine (e.g. from NAC or L-Cysteine supplementation) and glucuronic acid (e.g. from Kombucha). Adequate amounts of these molecules are necessary for proper detoxification ability.

Without sufficient cysteine or cystine intake, or conversion (which may be low in those with low mitochondrial function), glutathione cannot be manufactured in any significant quantity by the body, which will hugely impact the liver's ability to perform its detoxification functions, as well as the body's antioxidant defenses as well as the body's capacity for cellular respiration. It is possible to supplement reduced Glutathione orally or have reduced Glutathione injections. Most Glutathione supplements are destroyed in the stomach, but a few types are stabilised, e.g. Integrative Therapeutics, Inc.'s Tyler Recancostat 100 (an anti-cancer supplement); or perhaps slightly less so, ThioDox by Allergy Research Group (which contains 250mg NAC, 200mg L-Glutathione (Reduced) and 150mg of Lipoic Acid) - see the Links page for more information.

The purpose of Phase I and II reactions is to render toxins less harmful and also more water soluble, so they can be more readily and safely filtered, transported and removed from the body.

Research into the detoxification processes shows that the function of the enzymes that control the Phase I and Phase II processes may vary significantly from person to person (Patel et. al., 1992). So this means an individual's functional capacity to detoxify toxic materials can present in different forms. This can relate to factors such as inherited or genetic strengths and weaknesses in a person's biochemical pathways, which can be either improved or slowed down, by many environmental or nutritional factors.

This to some extent genetic, biochemical basis for the wide ranging detoxification capacities may explain the diverse responses individuals have when exposed to chemicals, drugs and even foods that many individuals may find they have adverse reactions to.

The Cytochrome P450 enzyme systems that carry out this detoxification process are a large family of isoenzymes also known as mixed-function-oxidase enzymes. They organize the biotransformation or conversion of fat-soluble substances, such as petrol fumes inhaled while at the service station or medication and recreational drugs, and convert them into intermediate compounds that have increased water solubility.

These enzymes provide the body with its ability to process and remove compounds that could change or even damage the function of cells. It is perhaps understandable that many types of these enzymes are concentrated in the mitochondria or energy-producing component of our body's cells. With mitochondria present in muscle cells, nerve cells and brain tissue as well as cells in all the body's organs, it could be expected that a build up of any compounds capable of affecting tissue function by either slowing or speeding up mitochondrial performance could exert a profound effect on an individual's health.'


Toxins prior to Phase I Treatment are non-polar, lipid soluble (i.e. harder to move/manage). Lipid-soluble toxins are usually stored in fat cells (adipose tissues) and contribute to increased/mobilised toxin load.

The Excretory Derivaties are polar and water-soluble. They are excreted either by the gall bladder in the bile into the digestive tract (for excretion via the faeces/stool) or returned into the blood serum and are filtered out by the kidneys and removed from the body in the urine.

In general, detoxification is performed in the body through a Phase II enzyme-catalysed (glutathione S-transferase) process in the liver, where lipophilic (lipid loving) toxin molecules are bonded with hydrophilic (water loving) sulphur-based molecules (i.e. glutathione). The bonding of glutathione with toxin molecules is not a random occurrence of molecule collision (brownian motion) in the blood stream. In this combination state, the liver and gallbladder are more easily able to remove them and to excrete them into the digestive tract as part of the bile, where hopefully they are completely eliminated from the body via the anus.

A summary of Phase 1 & 2 Enzymatic Functions can be found at the links below.

www.arlaus.com.au/library/file/7/Functional_Liver_Detoxification_Profile_FLDP_IG.pdf

http://www.livingnetwork.co.za/healingnetwork/liver_detoxification.html

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Phase 1 & 2 Enzymatic Function Summary:

PHASE I REGULATION (Cytochrome P450 Enzymes):

Reactions:
- Oxidation
- Reduction
- Hydrolysis
- Hydration
- Dehalogenation (removal of halogen molecules, e.g. Chlorine etc.)

Unless there are sufficient antioxidants and protective nutrients, the Superoxide (O2-) may result in Free Radicals that may cause Secondary Tissue Damage (Oxidative Damage).

Enzymes, Cofactors & Other Nutrients Used:
Please note that the co-factors listed below are essential for proper liver function.
- Vitamins B2, B3, B6, B12 and folate.
- Glutathione (glycine, glutamine and cysteine) or NAC (N-Acetyl Cysteine).
- Branched chain amino acids (leucine, isoleucine and valine).
- Selenium
- Manganese
- Vitamins C and E
- CoEnzyme Q10
- Flavonoids (Quercetin - found in Hawthorn, red grapes, capers, red onion, broccoli and broccoli sprouts (i.e. the long lasting antioxidant Sulphoraphane Glucosinolate) (certain broccoli strains yield a higher SG content, which has been trademarked SGS, e.g. Xymogen Oncoplex, Jarrow Formulas' BroccoMax or Brassica teas), citrus fruit, etc.)
- Bioflavonoids (green tea catechin, Silymarin (Milk Thistle/St Mary's Thistle extract), and Ginkgo.
- Phospholipids (in particular Phosphatidyl Choline)
- Naringenin (glycoside found in grapefruit juice) will slow Phase 1 down in the gut.

INTERMEDIATE METABOLITES:

Intermediate Metabolites are more polar and more water-soluble than the non-polar and lipid soluble toxins (pre-treatment). Unless there are sufficient antioxidants and protective nutrients, the Reactive Oxygen Intermediates may cause Secondary Tissue Damage (Oxidative Damage).

Antioxidant/Protective Nutrients/Plant Derivaties:
Please note that (at least some of) the antioxidants listed below are essential for liver protection.
- Vitamins A, C & E
- CoEnzyme Q10
- Essential (and protective) Minerals such as Zinc, Selenium, Magnesium and Manganese
- Thiols (found in Garlic, Onions & cruciferous vegetables).
- Flavonoids e.g. Quercetin; or Luteolin (found in Dandelion).
- Bioflavonoids (green tea catechin, Silymarin (Milk Thistle extract), and Ginkgo.
- Pycnogenol
- Omega 3 Fatty Acids etc.

* Up-regulation of Phase 1 will cause an increase in free radical production and activity.
Antioxidants will help prevent cellular damage caused by free radicals.

PHASE II REGULATION (Conjugation Pathways):

The Phase II conjugation pathways are essentially additions of organic group compounds to the toxins/waste to make them easier to remove from the body. Some sources refer to 4 main Phase II Conjugation (addition) pathways, others to a full 6 or 7. The main 4 are listed first in the list below.

Glutathionation (Glutathione Conjugation):
- N-acetylcysteine (precursor to GSH synthesis and enhances glutathion-S-transferase activity); also supports sulphation conjugation (sulphur donor), Glutamine and Glycine.
- Cysteine and Methionine are also precursors to GSH synthesis.
- Selenium (forms part of the Glutathione enzyme)
- B6, B12, Folate (involved in the methylation and production of Glutathione).
- Carnosol and camosic acid (Rosemary), Curcumin (or Turmeric) (may inhibit Phase I - use only when Phase I is normal).
- Indole-3-Carbinol

Sulphation:
- Organic sources of Sulphur including Sulphur containing amino acids (cysteine, cystine, methionine and taurine), Vitamin A, Adequate protein, Garlic and onions, and Brassica family vegetables.
- Inorganic sources of Sulphur including Magnesium sulphate (epsom salts), Sodium sulphate, etc.
* Both organic and inorganic forms of Sulphur are required for proper Sulphation.
- Molybdenum - is a trace element required in the conversion of sulphites to sulphates.

Glucuronidation:
- Calcium D-Glucarate - this is the Calcium salt of D-glucaric acid, which is produced endogenously and also found in a variety of fruits and vegetables. Studies have shown that high doses of Calcium D-Glucarate inhibit beta-glucuronidase, thereby enhancing the process of glucuronidation.
- Glucuronic acid (e.g. found in Kombucha, Kombucha extract; and also in Artichoke, or Artichoke Extract - true Artichoke, the green thistle, not Jerusalem Artichoke the root crop)
- Magnesium
- Essential fatty acids (EFAs)
* Glucuronidation is the process in which foreign organic compounds, fat-soluble toxins and excess steroid hormones such as estrogen are detoxified and excreted from the body.

Acetylation (Acetyl Conjugation):
- N-Acetylcysteine (NAC); addition of Acetyl group to toxin molecule.
- Acetyl L-Carnitine
- Pantothenic Acid (Vitamin B5)

Glycination:
- Glycine, e.g. Gelatin is a rich source of Glycine (being composed of 33% Glycine). Glycine is attached to nutritional elements such as Magnesium in Magnesium Glycinate supplements. Glycine is available supplementally and also as part of amino acid supplement powders, e.g. Thorne Research MediClear or MediClear Plus.
- Glutamine
- Ornithine
- Arginine

Other Amino Acid Conjugation:
The following amino acids are used in amino acid conjugation:
- Taurine
- Glutamine
- Arginine
- Ornithine

Methylation:
The biotransformatin of homocysteine to methionine is supported by methyl donors (methionine conjugation), such as betaine (e.g. found in high concentrations in beetroot), folic acid and adenosylcobalamin (B12). See below for more information.

Please see the Liver and Gallbladder Support section of the Detoxification Protocols page for more information on herbs related to liver support.

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Glutathione and Methylation:

Gluthatione is pronounced 'gluta-thion'. It's full chemical name is N-(N-L-gamma-glutamyl-L-cysteinyl)glycine and is sometimes abbreviated to GSH. (Reduced) Glutathione (GSH) is a naturally occurring protein, is called a peptide. It is composed of three amino acids, Glycine, Glutamine and Cysteine. Cysteine contains sulphur and gives glutathione its sulfuric aroma. It also plays a major role in glutathione's antioxidant and detoxification functions. In its oxidised form it is known as GSSG. Oxidised Glutathione is regenerated to the reduced state (the antioxidant enzyme form) by the action of the Glutathione reductase enzyme.

Glutathione is one of the body's natural anti-viral pathways. It can be boosted indirectly by increasing mitochondrial (energy) production or by taking precursors to Glutathione such as MSM, NAC or Lipoic Acid, or indeed directly by Glutathione injections (often combined with Phosphatidyl Choline to restore oxidised cell membranes).

Please see the link below for more information about Glutathione.

http://en.wikipedia.org/wiki/Glutathione

www.readisorb.com/glutathione_information.html

Below at the PhoenixCFS site is a good overview of Glutathione production and usage in the body.

http://phoenix-cfs.org/GluAACFS04.htm

Whilst Glutathionation and Methylation are two distinct processes in the Phase II Regulation in the liver, Glutathione itself is produced by Methylation, so a problem with the methylation pathway will affect Glutathione production and Glutathionation capability of the liver as well as the Methylation pathway in the liver.

Please see the Homocysteine Metabolism, Methylation & Glutathione Production section of the Nutritional Deficiences page for information regarding the methylation cycle and Glutathione production, and also supplementation to assist liver and detoxification function.

Please also see the rest of the Nutritional Deficiences page for more information on B-Vitamin requirements and deficiencies.

Glutathione production may well be very low in someone with CFS or related conditions. It is often one of the biggest bottlenecks in a person's ability to detoxify their body. Low Glutathione levels are often seen in sufferers of CFS and FMS, and other conditions such as MS, ALS, Alzheimer's disease and Parkinson's disease.

www.themaxsite.com/glutathione.html

www.themaxsite.com/benefits.html

www.nutritional-healing.com.au/content/condition.php?condition=CFS%2FFMS

Below is an audio file of a talk by Betsy Hicks, John Hicks, MD, and Tim Guilford, MD, discuss the role of glutathione.

www.readisorb.com/hear_about_glutathione.html

The link below is a Review of Dr. Cheney's paper 'Glutathione Deficiency in ME/CFS/CFIDS' by Philipa D. Corning, CD, B.Sc. (Hon), Ph.D.

www.mefmaction.net/Patients/Articles/Treatment/GlutathioneDeficiency/tabid/236/Default.aspx

We can assist the body by consuming precursors to glutathione, such as MSM (methylsulfonylmethane) or NAC (N-Acetylcysteine or N-acetyl-L-cysteine). Only very high quality and expensive glutathione supplements will actually reach the blood stream as glutathione, e.g. Tyler's Recancostat or Allerg Research Group's ThioDox. Most glutathione supplements are simply broken down in the GI tract (as with other bodily produced antioxidant supplements like SOD etc.), so their benefit is minimal. Glutathione can be injected intravenously, and is usually injected with Phospholipids as part of IV Phosphatidyl Choline treatment. Please see the Phospholipid Therapy section below.

We may also wish to consider L-Cysteine and/or L-Methionine. Please see the Cysteine and Cystine section on the Nutritional Deficiences page for more information.

A possible exception to the above regarding orally ingested gluathione is the product by Readisorb 'Liposomal Glutathione'. This is reputed to contain 'reduced L-Glutathione'.

www.readisorb.com/readisorb_liposomal_glutathione.html

Garlic is also a good source of sulphur and assists in binding with toxic chemicals. Consuming too much raw garlic can of course result in too much hot energy in the body (c/f TCM). In specific cases, partial detoxification products like glutathione conjugates, organic sulphate conjugates or peptide complexes may become bound to the mitochondrial membrane (for example glutathione bonded with organic chemicals or drugs like antibiotics), in which case their removal may be more complicated.

PhoenixCFS has a good overview of supplementation that can help to boost Gluathione production.

http://phoenix-cfs.org/Glutathione%20Building%20in%20CFS.htm

Silymarin, the active ingredient in Milk Thistle, actually helps to intially coat the liver cell walls and helps to prevent from toxins entering into them. Its antioxidant properties then neutralise any free radicals present that are causing the damage to the liver cells. Click here for more information. The role of milk thistle is discussed elsewhere on this page.

Factors that can assist gallbladder function (specifically) include Phosphatidyl Choline, Lipase, Vitamin C, Vitamin E and Pancreatin, as well as various herbs (which also support Liver function).

http://www.suzannes.com/galdis.html

There are a number of combination products contain rice protein, a number of added amino acids, Glutathione precursors, minerals, trace elements, vitamins and free radical scavenging antioxidants. One example includes Thorne Research's MediClear Plus, as discussed on the Nutritional Deficiencies page.

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Glucuronidation and Gilbert Syndrome:

The process of Glucuronidation is the enzymatic addition of the Glucuronate ion to organic toxins and other compounds that are being processed for excretion from the body. Glucuronate is a salt or ester of Glucuronic acid. Glucuronic acid is extremely soluble in water, and the process of Glucuronidation renders a compound more water soluble, allowing excretion from the body through urination or faeces. The products of Glucuronidation are known as Glucuronides (or Glucuronosides).

http://en.wikipedia.org/wiki/Glucuronic_acid

'Glucuronic acid is highly soluble in water. In the animal body, glucuronic acid is often linked to the xenobiotic metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds, and this linkage process is known as glucuronidation. Glucuronidation occurs mainly in the liver, although the enzyme responsible for its catalysis, UDP-glucuronyltransferase, has been found in all major body organs, e.g., heart, brain, kidneys, adrenal gland, spleen, and thymus.[2] UDP-glucuronic acid (glucuronic acid linked via a glycosidic bond to uridine diphosphate) is an intermediate in the process and is formed in the liver.'

Clearly there are many different processes involved in Phase II Conjugation in the liver, Glutathionation and Methylation are only two of these. They tend to receive the most attention from scientists and researchers into liver dysfunction and CFS, but Glucuronidation is an extremely important Phase II Regulation Process. Glucuronic acid is derived from the glucose molecule. An ache in the Liver/Gallbladder area is often indicative of an impaired Glucuronidation function, according to one of my sources. An elevated Bilirubin level in the urine may also be indicative of this. Glucuronidation dysfunction can be allieviated by supplying the body with more Glucuronic acid or Calcium D-Glucarate. Magnesium and EFAs are also essential factors, as with numerous other bodily processes and it is likely that you will already be supplementing these.

Sources of Glucuronic Acid include:


Besides supplementation with Glucuronic acid sources, an indirect way to increase the Glucuronidation activity in the body is by the following.


What is Bilirubin?

Bilirubin is the yellow breakdown product of normal heme catabolism, i.e. the breakdown of hemoglobin from red blood cells (RBCs). It is created in the spleen where old or damaged red blood cells are disposed of. Bilirubin is a waste product that requires removal from the body, where largely occurs in the liver. Bilirubin, as mentioned above, is conjugated in the liver to Glucuronic acid, as part of Glucuronidation. Conjugated bilirubin is excreted largely in bile (moving out of the body through the digestive tract) and is responsible for the yellow colouration of bruising. Most of this conjugated bilirubin is disposed of through the digestive tract, where it is metabolised by colonic bacteria to form a brown colour. A small amount of conjugated bilirubin is removed from the body in one's urine, its yellow pigmentation making much of our urine yellow in colour.

http://en.wikipedia.org/wiki/Bilirubin

What is Gilbert Syndrome?

Gilbert Syndrome is a genetic condition that occurs in 5% of the population, particularly in the USA and Europe, where there is a genetic mutation in the promoter region of the UGT1A gene (on chromosome 2q37) for the liver enzyme Uridine-diphosphate-glucuronosyltransferase isoform 1A1 (a.k.a. UDP Glucuronosyltransferase 1A1 or UGT1A1). The UGT1A1 enzyme is responsible for the Glucuronidation of Bilirubin. In those affected with Gilbert Syndrome, there is approximately a 70-75% reduction in the glucuronidation activity of this enzyme, meaning that Bilirubin levels are somewhat elevated over normal. Bilirubin levels are generally more concentrated during periods of dehydration (urine more golden). Elevated urinary bilirubin levels may be a general indicator of temporary Glucuronidation impairment, or it may be an indicator that a person has Gilbert's Syndrome. Bilirubin levels can normally be measured (in a quick and dirty fashion) with a Liver Disease home testing kit.

Extremely elevated levels of Bilirubin are referred to as Hyperbilirubinemia or Jaundice. Elevated Bilirubin levels may result in a yellow pigmentation in one's eyes, and also in one's tissues. It should be noted that a yellow skin pigmentation in the head/face may also result from excessive consumption of Beta Carotene, found in carrots and Spirulina, for example.

www.medicinenet.com/gilbert_syndrome/article.htm

http://themedicalbiochemistrypage.org/gilbert-syndrome.html

'Bilirubin has been shown to inhibit DNA synthesis, uncouple oxidative phosphorylation, and inhibit ATPase activity in brain mitochondria. Bilirubin also inhibits a variety of different classes of enzymes including dehydrogenases, electron transport proteins, hydrolases, and enzymes of RNA synthesis, protein synthesis and carbohydrate metabolism. All of these toxic effects of bilirubin are reversed by binding to albumin. In fact, albumin plays a vital role in the disposition of bilirubin in the body by keeping the compound in solution and transporting it from its sites of production (primarily bone marrow and spleen) to its site of excretion which is the liver.'

http://en.wikipedia.org/wiki/Gilbert_syndrome

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Fructose Metabolism and Hereditary Fructose Intolerance:

The liver has many other functions besides the breaking down of fats and toxins and the removal of waste from the blood. One of its other roles is in the metabolism of Fructose and Gluconeogensis. Hereditary Fructose Intolerance (HFI) is a genetic condition whereby a deficiency in the liver enzyme Aldolase-B prevents normal fructose metabolism and gluconeogenesis occurring in the liver, and the build up in the substrate Fructose-1-Phosphate in the liver and kidneys. Inhibition of gluconeogenesis results in lactic acidosis as the cells underogo anaerobic respiration in the absence of glucose (i.e. Hypoglycaemia). The liver may try to compensate by producing glucose from the SCFAs Acetate, Propionate and Butyrate that are produced by the bacterial fermentation of dietary fibre. Rapid depletion of SCFAs in blood plasma is associated with HFI and can be detected with this blood test. Hypoglycaemia or more specifically HFI and related liver disorders, may be one contributary factor to inefficient liver function. HFI is discussed in more detail on the Food Allergy and Intolerance page.

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Gallbladder Function:

Your liver produces roughly a litre or a quart of a yellow/green liquid called bile each day that emulsifies and absorbs fats in the small intestine. Bile comprises of water, bile acids and pigments, lecithin, bilirubin, lipids, cholesterol, sodium, potassium, and chloride. The liquid is stored in the gallbladder, close to the liver, from where it is secreted to the intestinal tract as needed during digestion. Bile release takes place naturally when we are eating.

See the definition of bile on wikipedia at the link below.

http://en.wikipedia.org/wiki/Bile

See the link below for diagram of the gallbladder and how it connects to the liver and small intestine.

www.nlm.nih.gov/medlineplus/ency/imagepages/19261.htm

See the definition of the gallbladder on wikipedia at the link below.

http://en.wikipedia.org/wiki/Gallbladder

Certain herbs also help to increase bile production, such as peppermint and milk thistle, but the most important herb is Cilantro. Cilantro is also a powerful mobilisation agent for heavy metals.

Beetroot, mentioned above for its various compounds in aiding liver function, also has the property of increasing bile production. It can be taken in the form of raw/cooked Beetroot or Beetroot powder/extract (e.g. Metabolics' Beetroot). Ox Bile Extract (45-50% Cholic Acid) may also help with bile production (e.g. Vital Nutrients' Pancreatin & Ox Bile Extract which also contains Pancreatin providing the digestive enzyme groups Protease, Amylase and Lipase).

Phosphatidyl Choline (lecithin), is a key component of bile, and Phospholipid supplementation may greatly increase bile production.

The non-essential amino acids Taurine and Glycine are important constituents of bile. If the body is deficient in either of these amino acids (through wasting of Taurine for example, or insufficient production/conversion), it may impact bile production. Supplementation of deficient amino acids may help.

Both Cilantro and Phosphatidyl Choline are discussed in detail on the Detoxification page.

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Herbs to Support the Liver, Kidneys and Digestive Tract:
 
Liver and Gallbladder Support:

When it comes to detoxification, in addition to the nutrients mentioned above, the most important of herb in maintaining liver health and protecting the liver is probably Milk Thistle (Silybum marianum - seen above) . Milk Thistle is relatively neutral (warm not hot) in energetic terms (c/f TCM) and may be taken throughout the course of one's detoxification programme. Silymarin, the active ingredient in Milk Thistle seeds, actually helps to intially coat the liver cell walls and helps to prevent from toxins entering into them. Its antioxidant properties then neutralise any free radicals present that are causing the damage to the liver cells. Click here for more information. Milk Thistle can be purchased in the form of a tincture, tablet form and also as raw seeds (which can be crushed, and steeped as a tea or chewed/eaten). Jarrow Milk Thistle is a good choice of Milk Thistle supplement.

Other herbs (not mentioned in the above sections) that may help cleanse/support the liver and gallbladder include:

* = antimicrobial

It is with regret that I am not able to integrate the herbs in this section into the above section on Phase I and Phase II Liver Pathways, so one could pinpoint which liver pathway each herb would assist with. However, hopefully in the future, with further information, this may be possible.

Many of the above herbs are antimicrobial in nature too, to help kill off bad bacteria, Candida and parasites (e.g. Oregon Grape root, Wormwood, Black Walnut, Garlic and Fennel).

These herbs can be found for example in Dr Schulze's Liver/Gallbladder Formula. Christoper's Original Formulas' Blood Stream Formula also contains some of the above herbs.

Liver/Gallbladder Formula

Detox Tea

Detox Formula

A variety of Chinese herbal formulas may also be used for liver support (subject to TCM Practitioner recommendation/prescription) including:

The following herbs may help to support the Gallbladder, as well as the liver:

Enteric-coated peppermint oil may help dissolve gallbladder stones. Gallbladder stone flushes, a more severe method of removal, are described are on the Detoxification page.

http://www.suzannes.com/galdis.html

Thorne Research's Lipotrepein, a liver detoxification support formula, contains a number of co-factors and nutrients to support methylation and also herbs to promote bile production. The ingredients are:

Thorne Research Lipotrepein information page

Please see the Liver page with regards to supplements and antioxidants that can assist withLiver Function.

Whilst the herbs and supplements described above help to support liver function on a daily basis, they will not really clean out the gallbladder of mineral deposits and fat in the same way that a full Liver and Gallbladder Cleanse program will. Enterically coated peppermint oil is perhaps the exception. These herbs however may play a support role in such a programme.

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Kidney and Bladder Support:

The kidneys perform work based on the amount of dissolved substances they have to remove and the amount of urea they have to produce from amino acids in the blood. In the case of sore or tired kidneys, reducing mineral supplement intake and protein intake in general will help to alleviate the kidneys' workload. In addition, amino acid supplementation may aggravate the kidneys further, but it depends on how much protein you are also ingesting, and you may be able to get away with low level amino acid supplementation in those aminos you are chronically deficient in (i.e. splitting up a light dosage into smaller dosages and take periodically throughout the day rather than in one go), if your protein intake is otherwise low. Protein is digested slowly, releasing amino acids into the bloodstream over time whereas amino acids are absorbed very quickly (and usually taken on an empty stomach), creating spikes in levels of specific amino acids.

Diuretics help the kidneys by encouraging fluid loss through the kidney, thus promoting urination. It is important to drink enough water when taking diuretics as a result. Thinner blood is also easier to filter for the kidneys. Celery, Dandelion, Nettle and Burdock are known to stimulate the kidneys and reduce the toxicity symptoms associated with inefficient liver function and uric acid build up in the joints and muscles, which causes aches and pains.

Drinking sufficient water or herbal teas of the above herbs, e.g. dandelion, nettle and burdock, is also likely to be of benefit for the kidneys.

Vitamin C and indeed other antioxidants may well help the kidneys, and they are also wasted through the kidneys, ensuring they always reach the kidneys.

Traditional Herbal Medicine and Chinese Herbal Medicine (TCM) holds that Cranberries or Cranberry extract is useful for supporting the kidneys and bladder, and for protecting these organs from infection. TCM holds that Cranberries are useful for removing excess heat from the bladder.

Urva ursi, goldenseal, juniper berry, parsley root, marshmallow root, lobelia and cornsilk are all diuretics and are known to remove particles adhered to the kidneys and urinary tract. Urva ursi, goldenseal and juniper berry are also strongly antimicrobial and will help to eliminate kidney or bladder infections. Urva ursi and lobelia however are harmful to the liver, so high dosages should not be taken and not for extended periods. Another method of eliminating kidney or bladder infections is to take the wood sugar D-mannose, dosed regularly (e.g. 1tsp every 2 hours) for 24-48 hours - the sugar is eliminated through the kidneys where bacteria will tend to stick to it and be flushed out in the urine.

Be aware that diuretics increase urination and as such it is important to drink enough water when taking diuretic herbs and also to supplement potassium as potentially high rates of urination may deplete one's potassium levels. A number of diuretic herbs are also laxative in their effect, so please check the ingredients of the formula you are taking, and take into account what other laxative products or herbs you are taking in addition, as it may result in diarrhea if you are not careful.

Please see the Detox page for information pertaining to Kidney Flushes and Eliminating Kidney Stones.

A number of herbs, known as Blood Cleansers or Blood Purifiers help to boost blood circulation and help to cleanse the blood (by stimulating the liver and kidneys). If the liver is working efficiently and the blood is cleaner, it will alleviate the workload on the kidneys. Of course, certain particles are small enough to be eliminated by the kidney rather than the liver. Some of the blood cleansers are however contraindicated for kidney disease, e.g. Chapparral, so be cautious. These include:

- Red Clover
- Honeysuckle Flower
- Yellow Dock Root
- Siler Root
- Echinacea pallida
- Sarsaparilla Root
- Chinese Skullcap Root
- Ginger Root
- American and Asian Ginseng Root
- Ginkgo Biloba
- Licorice Root
- Prickly Ash Bark
- Buckthorn Bark
- Peach Bark
- Oregon Grape Root (also antimicrobial)

Many of the above can be found in Planetary Herbals' Red Clover Complex.

www.planetaryherbals.com/products/GP1542/

EU law currently prevents the usage of terms of as Blood Cleanser and Blood Purifier on herbal products. These terms are arguably rather vague anyway, and should really refer to their actual effect on the kidneys.

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Digestive Support:

As the liver is involved in digestion and bile production, but definition, certain herbs that support the liver and stimulate bile production will also play a role in assisting digestion. However, this section is mainly concerned with stimulating peristaltic action (a.k.a. peristolic action). Herbs that stimulate the production of stomach acid, that relax the walls of the intestines and that stimulate peristaltic action are examined on the Digestive Disorders page in the Herbs section.

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General:

Each herb has a specific purpose and a specific mixture of herbs may be recommended by your specialist. Herbs come in the form of additions to detoxification supplements, in detoxification herbal teas (available in packets of tea bags from your local health food shop or supermarket) and also from specialist herb suppliers such as HerbCare. Whilst such herbs may indeed help, they also have energetic properties (c/f Traditional Chinese Medicine theory) that may imbalance the body if used long term.

Consult your doctor or consultant for advice with respects to dosage. With regards to the other herbs mentioned above, one may elect to take very small amounts of these herbs as part of one's overall detoxification programme to assist in the overall process or one may choose not to. Drinking herbal teas results in excessive staining of your teeth. Your hygienist may not appreciate it!

Some specialists recommend special diets and juice fasts in combination with herbal products, whilst others suggest supplementation with specific herbs, whilst engaging in a restrictive but more balanced diet and some or all of the procedures discussed above on this page with regards to cellular detoxification and cleansing of the detoxification pathways.

The quality and strength of herbs may vary from supplier to supplier. In general, fresh, organic herbs are ideal. Tinctures in general tend to be more readily absorbed than dry capsules. Whilst the leafy parts of a plant may be readily absorbed in the form of a tea or when consumed as a capsule, the roots of plants are much harder and may not be absorbed very well, even when ground up, and so may require prolonged boiling (or their vital ingredients extracted using alcohol). This is why many Chinese herbs are boiled for 30 minutes prior to consumption. Some hold that using deionised water is optimum as it is likely to absorb more nutrients from the herbs than is ordinary mineral/filtered water. This may not however be very practical!

Lower quality herbal products often use cheaper sources of the herbs, which may be of low quality/grade, the highest quality herbs going to premium suppliers; they may be poorly harvested, out of season, even old; poor crops may be used, which would not be used by reputable suppliers; the herbs or plants may indeed be poorly or carelessly processed, or over-cooked/burnt/processed, resulting in tinctures and products with very low levels of active ingredients present. Slightly cheaper or less potent variants of herbs or plants may be used. Non-organic herbs may be lower in active ingredients in any case and coated with small concentrations of herbicides and pesticides.

My friend Aaron has personally tried all of Dr Schulze's main cleanses, the Liver cleanse, the Kidney cleanse and the Bowel cleanse, and whilst all three cleanses seemed quite good, he still had issues in all three areas subsequently. So Aaron remains slightly sceptical about the claims made by Dr Schulze with regards to his products in these areas; but without examining what issues were present before and after, an analytical review is not really possible at this stage.
Please note that there are a number of other nutrients, probiotic byproducts (e.g. Kombucha) and amino acids that can be taken to support liver function. These are discussed in more detail on the Inefficient Liver Function page. The above is just a selection of those that are strictly herbal in nature.

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Factors that may contribute to Inefficient Liver Functioning:

Please see the Introduction section of this page, and also the Various Possible Triggers Implicated In CFS section for an overview of the possible pathways to liver impairment.

The efficiency with which the liver perform its various tasks depends upon a person's general health, his level of energy (c/f Traditional Chinese Medicine), how many toxins, mineral and fat deposits it currently contains, the provision of sufficient antioxidants, B-vitamins and nutrients/cofactors (e.g. Glutathione precursors) in the blood supplied to the liver (which is determined by diet and digestive function) and their actual presence/ability to permeate the mitochondrial membranes where they are needed, the level of hydration of the blood and tissues, the electromagnetic health of the cells in the body, general mitochondrial efficiency, the dietary intake of fats, and how many toxins (e.g. drugs, alcohol, neurotoxins etc.), chemical waste products and immune system waste products (e.g. white blood cells that have absorbed a bacterium or other parasite; or antibodies that have latched onto a virus) etc. are actually present in the blood that require processing/removal; and potentially genetic factors. If the organs have been overloaded with toxins for many months or years, their energy will gradually decrease until they are unable to efficiently cope with removing toxins from the blood. In such a condition, the patient may drink plenty of water (usually not ionised water), but efficient detoxification will not occur. It is in such circumstances that we have to intervene to assist the natural detoxification pathways of the body.

The liver should be filled with water and contain little fat. In those with diets high in saturated fat and trans fat, and high body fat percentages, the liver may be enlarged and full of fat. In extreme cases their liver may resemble a goose's liver that is prepared for fois gras! Such geese are force fed corn or maize, and have a liver that is almost 10 times the size of a healthy liver. The liver is almost purely made up of fat. The liver function of such birds is extremely impaired. This is what happens to human livers in extremely unhealthy individuals over time on a slightly lesser scale.

Please see Dr Sanda Cabot's web site Liverdoctor.com's report on the fatty liver below.

www.liverdoctor.com/index.php?page=fatty-liver

Liver damage also occurs on account of excessive alcohol consumption. The average level of alcohol consumption in the UK has doubled since the 1960s. Most people who drink regularly are blissfully unaware of the damage they are causing to their livers, and are regularly overloading their livers with high saturated fat levels as well as excessive alcohol levels (and the usual high levels of toxins from environmental sources, commercially available non-organic food sources, poor cooking practices, stimulants (coffee etc.), medicines and bath room products that the liver must process). The daily recommended safe limit for an adult female is 2-3 units and the daily recommended safe limit for an adult male is 3-4 units. However, this does not mean that all these units should be drunk all at once, and that one can drink more safely on one day as one did not have anything the previous day. Regular drinking over these limits, as well as the other factors discussed, will contribute to the onset of liver disease (for which there are often no visible symptoms). The liver is able to self-repair itself up to a certain point, but the stage where people usually discover they have liver problems is when this point has been long passed and where permanent damage has occurred.

www.patient.co.uk/showdoc/23068925

http://en.wikipedia.org/wiki/Liver_disease

For more information on fat intake and fat types, please see the Digestive Disorders and Nutritional Deficiencies pages.

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Effects of Inefficient Liver Function:

Signs that a liver is not coping or keeping up with its demands facing it include skin problems such as 'liver spots, discoloured skin patches, excessive wrinkling, the appearance of acne, spots or boils, generally together with fatigue and lethargy.

Inefficient liver functioning (and chiefly low Glutathione production, rapid Glutathione depletion and poor Glucuronidation) can lead to 'metabolic poisoning', i.e. the build up of metabolites within the cells, tissues and organs of the body that have not been processed by the liver and excreted. Quoted from ARL Pathology's Web Site (see the pdf for the full article and related diagrams):

www.arlaus.com.au/clinical_guides/FLDP%20Guide.pdf

'Inefficient liver function can lead to 'metabolic poisoning' which is a nondescript term referring to the build up within cells, tissues and organs of metabolites which have not been processed by the liver and excreted. These metabolites alter the pH gradient and electrolyte profile within cells and can serve as competitive enzyme inhibitors that ultimately interrupt effective bioenergetics within the cell. The symptoms of metabolic poisoning at the elevated level are reflective of poor energy dynamics and include fatigue, hypotonia [abnormally low muscle tone and strength] and brain biochemical disturbances. Recent studies have reported a relationship between impaired detoxification capability, mitochondrial dysfunction and chronic fatigue syndrome (CFS). These reports suggest that oxidative damage due to mitochondria and the detoxification process is itself a fundamental mechanism in the development of CFS.

Well recognised examples of metabolic poisoning include the symptoms of uraemia [kidney failure resulting in build up of urea and other toxins/acidic compounds in the blood resulting in lethargy and decreased mental functioning] or hepatic encephalopathy [inefficient liver functioning resulting in toxins accumulating in the blood and impairing brain cell functioning]. Both of these conditions are associated with fatigue and central nervous system disturbances and are a consequence of this metabolic poisoning of specific tissues due to the build up of toxins. Assessment of liver functional capacity for detoxification has been limited due to the potential invasive nature of a test. Cost and complexity of procedures have also limited routine clinical usage. Recently, functional liver challenge tests have evolved which can allow routine assessment of the liver's detoxification abilities.'

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