Liver function and neuromuscular system

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Liver function and neuromuscular system

Postby Floater on September 26th, 2003, 5:22 pm

i found this on a web site enjoy



Liver Function
and its
Possible Influence on Neurodegeneration


(ALS) Amyotrophic Lateral Sclerosis or (MND) Motor Neurone Disease are referred to as ALS/MND throughout.

I believe that liver function and the endocrine and immune systems may be involved in the progress of ALS/MND. As my research progresses I repeatedly find direct or indirect references to liver function being somehow implicated in the neurodegenerative process. By "tying up the loose ends" this is what I have found so far ...

Whilst researching the possible influence of anti oxidants and other readily available medications on the progress of ALS /MND certain metabolic processes, apparently unrelated to neurodegeneration, were repeatedly mentioned in medical texts and research papers. Whilst primarily researching anti oxidants I also read research papers by neurologists, cardiologists, virologists, cytologists, endocrinologists and numerous other medical specialists. In describing the process by which various anti oxidants were metabolised in order to affect various bodily organs and processes, the liver is repeatedly referred to in texts as either metabolising/separating or storing proteins, enzymes, micronutrients or vitamins.

Standard liver function blood tests may not always indicate liver dysfunction but this may be apparent in other ways. Poor liver function may be the cause of frequent bad breath, abdominal bloating, poor digestion, fatigue, headaches, unpleasant moods, coated tongue, sluggish metabolism, poor immune system, excessive body heat, sugar cravings, inability to loose excess weight and numerous other symptoms. To correct liver dysfunction you may have to adjust your diet (as explained below); increase hydration (drink 10 glasses of water daily); decrease or eliminate tea, coffee and alcohol intake; detoxify the liver (under supervision of a competent practitioner) and take a combination of supplements to aid in the repair and improvement of the liver.

Supplements that can be used to detoxify include NAC (N-Acetylcysteine), Silymarin, Burdock and Dandelion. Not everybody tolerates NAC well but Silymarin, Burdock and Dandelion have been used widely to improve and even cure mild to severe liver conditions. Information on some of these supplements can be found on the Medications or Anti Oxidant pages of this website. I would recommend that you consult a competent herbalist or naturopath if possible.

* It is interesting to note that research in 2002 revealed that "Gastrointestinal motor dysfunction can occur in amyotrophic lateral sclerosis, even if patients do not complain of gastrointestinal symptoms. New techniques in non-invasive evaluation of gastrointestinal function showed delayed gastric emptying and delayed colonic transit times in patients with ALS". This could place immense pressure on normal liver function. See: http://www.als-tdf.org/alstdf/research/ ... rticle=728

* If a standard liver function test does not reveal liver dysfunction in your case please note that in liver biopsies on ALS/MND patients doctors found bizarre giant mitochondria, intermitochondrial paracrystalline inclusions, disorganization of rough endoplasmic reticulum, increase in the endoplasmic reticulum and parasinusoidal fibrosis. Liver tests showed only mild dysfunction! Y Nakano, Hirayama and Terao 1987.

* Excerpt from a PALS' e-mail: "A [more comprehensive] liver function test came back from the Great Smokies Diagnostic Lab in the USA indicating that three of four phase 2 enzymes aren't working and I am unable to excrete toxins by making them water soluble (which explains a lot of my history). I gather there is a treatment that helps and which will hopefully reverse some of my food allergies. I knew it was a problem - more so than I thought though. I think your theory makes a lot of sense as I know my problem has existed for many, many years". R.E. Australia

* A paper describing the reversal of neurodegenerative symptoms in a patient after a liver transplant offers several explanations as to why they feel liver function may have a direct affect on neurodegeneration. "Reversal of parkinsonism following liver transplantation" Lisa Shulman, et al: Neurology Feb 2003



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Consider the Following:

* It is important to note that a standard liver fuction blood test may not show marked liver dysfunction until up 50% of the liver is effected!

* The liver is the largest gland in the body and a storage site for vitamins A, D, C and B12, riboflavin, pantothenic acid, folic acid, biotin and pyridoxine. In an adequately fed person the stored supply of vitamins A, D and B12 can be sufficient to last from 6 months to 2 years. All other vitamins must be replenished from dietary or supplementary sources every day or so. (See Diet).

* The liver activates and converts riboflavin, thiamine, pyridoxine, nicotinamide, pantothenic acid and biotin into phosphate complexes. It converts folic acid to folinic acid, vitamin B12 into its coenzyme forms, vitamin D into 25-hydroxy vitamin D and vitamin A into retinoic acid. These transformations by the liver are essential before vitamins can perform their metabolic functions.

* The liver synthesises inositol, choline and lecithin. It converts cholesterol into bile salts (dependent on vitamin C) and produces proteins needed for blood clotting (dependent on vitamin K).

* Diseases or dysfunction of the liver may cause excessive loss of B complex and other vitamins and also prevent uptake of vitamins and prevent activation of vitamins into metabolic forms.

Folic Acid - "Deficiency may cause subacute combined systems degeneration clinical signs can exist in the absence of Vitamin B12 in patients severely deficient in folate and these neurological signs remit during therapy with folate". (3)

Vitamin B3 - "Correction of low B3 appears to be very important for ALS patients since low B3 can per se cause bulbar palsy, paralysis, coma, etc." (10)

Vitamin B6 - "A 71 year old patient had a 12 year history of involuntary movements which began first in the arms and later spread to the rest of her musculature. Treatment with (vitamin B6)pyridoxine hydrochloride (IV then oral) She began to improve following the first few injections. After 3 weeks she was walking unassisted and with ease" (4) "Improvement was seen in patients with ALS/MND following IV administration of vitamin B6". (5)

Vitamin B12 - "Deficiency is known to result in subacute combined degeneration of the spinal cord (6)

Vitamin E - Deficiency is associated with progressive neurological deterioration. Diseases associated with vitamin E deficiency include chronic cholestatic liver disease" (7) "In occasional ALS patients especially those with vitamin E deficiency,the injection of (vitamin E) is effective, at least temporarily, in relieving neuromuscular symptoms. Occasionally the improvement is striking but it is difficult to measure objectively" (8)

Thiamine - "8/9 cases of ALS improved on (vitamin E) "enhanced" with thiamine" (9)

In the case of ALS/MND it would appear that, other than the brain and central nervous system, the liver could be the organ most likely involved (albeit indirectly) in the rate at which neurodegeneration takes place. Numerous substances thought to have the potential to aid in treating ALS/MND (some mentioned above) are metabolised, altered, stored or created by the liver. For example Insulin Growth Factor -1 (IGF-1 or "Myotrophin") is created in the liver and is currently being researched as a possibly beneficial substance in prompting nerve and muscle regrowth in ALS/MND patients (its normal function in a healthy person). Potentially beneficial proteins and amino acids are made available to the brain and central nervous system only after being transformed by the liver, for example N-Acetylcysteine or L-Cysteine are converted by the liver into glutathione. Glutathione is thought to be useful in regulating glutamate levels in the brain. Thickened/excessive glutamate is considered toxic to motor neurones (1 & 2). DMAE (di-methyl amino ethanol) is converted to acetylcholine (an important neurotransmitter) in the liver to choline.

Vitamins and minerals are produced or converted by the liver into their useful constituent parts. For example, beta carotene becomes available as an anti oxidant after being converted into vitamin A by the liver. The liver stores vitamin A and it is possible that vitamin A may be helpful in reducing the rate of oxidation of motor neurones. Chromium is involved in the creation of DHEA by the liver and DHEA is claimed to be an "anti aging hormone". (Nicotinamide, mentioned above, is a biological source of chromium). Rapid destruction of motor neurones through oxidation could loosely describe ALS/MND and destruction of motor neurones and other cells through oxidation is one of the most obvious causes of what we accept as the "natural" aging process. If this is correct then ALS/MND is analogous to rapid aging, particularly of the central nervous system.

My concern is that many neurologists are often not in a position to discuss patterns and aetiologies not directly related to their specialist field of medicine. It is unlikely that a hepatologist (liver specialist) or endocrinologist would attend a neurological symposium or that either the hepatologists/endocrinologist or neurologists would have identified a link between liver function and neurodegeneration (if indeed it can be proved that there is one). My personal opinion is that ALS/MND probably afflicts those with a genetic predisposition to the disease and that the liver's ability to cope with excitotoxins or to supply/synthesise/modify a person's metabolic requirements could dictate the rate of motor neurone deterioration. Only a full clinical study can possibly substantiate this theory.

Based solely on my own research, which in turn has included reading text books to diverse published research papers, I believe that there may well be a link between neurodegeneration and impaired liver function. As a consequence I have incorporated a "liver friendly" approach into my daily routine. I have ceased to take or reduced prescribed medications that are known to adversely effect liver function (as and where possible and after consultation with my doctor). I drink at least 10 x 400ml/15fl oz glasses of plain, filtered water daily in addition to other fluids [see next paragraph]. I have reduced or ceased to consume substances that are widely known to stress or adversely effect liver function. Some examples of common liver stressors (especially if taken to excess) are alcohol, caffeine, nicotine, animal fats, (excessive) protein, (excessive) dairy products, non steroidal anti inflammatory drugs (NSAIDs) and narcotic analgesics.

If ALS/MND is triggered by excessive free radical activity or toxic substances in the body it is essential that you drink sufficient water to aid the liver and kidneys to "flush" these from your body. Tea, coffee and alcohol act as diuretics and can promote dehydration if used in excess. Fruit juices can assist with hydration but plain water is even better. It is generally accepted that 2.5 litres of fluid per day is the recommended minimum intake for adequate metabolic function. Researching further I found a suggestion that you should drink a minimum of ten 15fl oz/400ml glasses of water per day in addition to other fluids. Some doctors and naturopaths recommend a water intake based on bodyweight but exact recommendations and ratios vary. If you find it difficult to drink a full glass of water drink smaller amounts but do so frequently. Drink before you feel thirsty if possible. [For those with swallowing difficulties large quantities of water may be difficult to consume but, if possible, attempt to devise strategies that will allow you to do so unless medically contraindicated]. The full benefits of increasing water consumption should be noted after 12 weeks.

Drink tea/coffee, carbonated soft drinks, milk and particularly alcohol as "treats" rather than as your primary fluid sources. Numerous studies, particularly in the field of sports medicine, stress the importance of adequate fluid intake to aid in removing metabolic toxins and suggest plain water is best. If, as I suspect, liver function is implicated in the rate at which ALS/MND progresses the more plain water you drink the easier it will be for your liver and kidneys to function adequately.

[I now drink a minimum of ten glasses (approx 4 litres/9 pints) of filtered water daily and my consumption (and any craving) for other fluids is minimal. I had a history of drinking both tea and coffee to excess and these were once my primary sources of fluid each day. I do not crave tea or coffee now but do not deprive myself of either if I feel like drinking them. 4 litres/9 pints may sound like a lot of water and I admit that I struggled to drink this amount for the first four days. Within two weeks I was drinking ten glasses per day with ease. Now it feels perfectly normal and I comfortably drink even more on hot days. A frequent need to urinate was a problem for the first week or so but this has now settled to what I would consider "normal"].

As I had a pre-existing chronic, disabling spinal injury prior to being diagnosed with a (possibly atypical) slow, limb onset form of ALS/MND, I had been taking NSAIDs and increasingly stronger and more frequent prescribed narcotic analgesics to control debilitating pain resulting from nerve-root damage and bone and disc pressure on the dura (spinal nerve sheath). With the diagnosis of ALS/MND I was also given baclofen and valium to help control violent fasciculations and muscle cramping. Since taking anti oxidants regularly I have been able to cease taking NSAIDs completely (due to the inherent anti inflammatory action of the anti oxidants). I have also been able to slowly reduce the analgesics and anti cramping/spasm medications.

I was naturally predisposed to a poor liver function (according to routine blood tests) prior to both accident or illness despite being a non-drinker and non-smoker who exercised regularly and extensively. Whilst taking analgesics and anti inflammatories my liver function consistently bordered on extremely poor to nearly inadequate. In an attempt to improve this situation (and lacking a viable conventional alternative) I was prescribed the herbs Burdock and Silymarin by a naturopath. Within two months my liver function registered "normal" for the first time in many years. When I stopped taking the prescribed herbs for several weeks, my liver function again tested poorly. On recommencing the herbs my liver function again returned to normal. Although not an active proponent of herbal or "alternative" medicine at the time I (and my doctor) found it difficult to ignore the empirical evidence confronting us. [Please contact a qualified naturopath/herbalist for assessment, dosages and prescription of herbal medications. A full assessment of your needs by a qualified and experienced practitioner is essential. I can make no recommendation by e-mail].

[Contributed byGC Victoria, Australia : "My case has always progressed more slowly than typical ALS but I would say that in the last six months or so that I have held my ground or even improved a bit. I tend on average to feel a bit stronger and freer and there have been occasional periods of a day or two lately where I have felt quite reasonable mobility wise. I have even occasionally taken a few steps without my walker.

My mental attitude plays a big part in all of this so it is hard to tell how much is true physical improvement due to all the anti-oxidants etc. and how much is due to slowly changing my mental attitude. One thing of interest is that the really good days have probably only started since I started the silymarin and burdock"]

Herbal medicine companies have been accused of manufacturing and supplying supplements or medications that are scientifically unproven. Many reputable herbal medication manufacturers have conducted or commissioned double blind placebo testing of many of their products [I have sighted numerous references and will append them here later].

It is interesting to note that ancient Arabic medicine (from which much current, conventional medical practice was initially derived) and traditional Chinese medicine, including acupuncture, both treat the liver in cases of neurodegenerative disorders. There is no such illness as ALS/MND recognised in China. Instead they treat a liver dysfunction that they believe causes the symptoms we know in western medicine as ALS/MND. A highly respected doctor and acupuncturist, Dr David Tai, wrote "Disorder of the liver may show itself in the central nervous system, the blood, the eyes, or may manifest as motor neurone disease (ALS/MND)". Tai D. Nature and Health:vol 7, No1, 1986

My increasing conviction that improved liver function may slow neurodegeneration was initially based on reading and assessing conventional and widely disparate medical texts and, at that time I was unaware of the Chinese and Arabic viewpoints.

* nb. I have received many e-mails from ALS/MND patients who were prompted by the information on this page to request full liver function blood tests. The majority of respondents reported that their liver function proved to be poor to seriously impaired. The few with liver function rated within the "normal" range still had room for improvement. It is important to note that a standard liver fuction blood test may not show marked liver dysfunction until up 50% of the liver is effected!

A test that may be applicable to ALS patients is the comprehensive liver detox test http://www.gsdl.com



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"The Liver Cleansing Diet" by Dr Sandra Cabot explains the role of the liver and offers suggestions and even diet menus to assist in improving liver function. For more information see http://www.whas.com.au . Although marketed as a diet book, it explains liver function clearly and simply and presents a compelling argument supporting the need to improve and maintain good liver function. Most of the fundamental information I struggled to assemble for this page is included in this book. I have recently read it and can recommended it highly.
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Avoid "Quick Fix" Liver Detoxification Techniques

There are several "Detox" diets and Liver Cleansing methods that include fasting, drinking quantities of olive oil and lemon juice. I would strongly suggest that PALS take a more gentle, slower approach to liver cleansing. In my opinion there are no safe, "quick fixes" for liver detoxification. PALS' livers are very probably under a great deal of pressure at the time of diagnosis. Quick fixes will severely stress an already over stressed liver. This is best avoided. SS



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Contributed by Allart Kok:

" Liver cells in ALS show a high percentage of mitochondrial abnormalities. There are fewer mitochondria, and they are swollen with many showing crystalline inclusions. Swollen, altered mitochondria are also found in the motor neurons of ALS, and are a rather general characteristic of degenerating cells. Crystalline inclusions are found in the neurons of other neurodegenrative diseases (they aren't unique to ALS). Their presence in ALS liver might indicate a wider systemic distribution of the disease, or as in some cancer patients, the liver may suffer collateral damage due to unknown factors released by the damaged/changed tissue. Altered tissues in ALS might release molecules such as interleukins or tumor necrosis factor, which might contribute to such changes. For example, I recall at least one report wherein spinal injury resulted in altered skin. I would not zoom in on the liver too fast. Skin is altered in ALS, too, and so are other, non-motor neurons, although the latter don't show a significant loss. It is important to emphasize to the ALS community that scientists don't usually publish negative findings unless they address some existing theory - you don't know whether anyone has looked at other cells. For this reason, I wouldn't jump to conclusions. It is conceivable that other, non-neural cells could be killed off elsewhere in the body, but these would be replaced, increasing 'cell turnover' - no one knows. It is clear, however, and most significant, that motor neurons, among all neurons, are the most vulnerable to being killed off.



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Chronic mitochondrial inhibition induces selective motoneuron death in vitro:
a new model for amyotrophic lateral sclerosis.
Kaal EC; Vlug AS; Versleijen MW; Kuilman M; Joosten EA; Bar PR J Neurochem 2000 Mar;74(3):1158-65
Laboratory for Experimental Neurology, University Medical Center Utrecht, The Netherlands.
PMID: 10693948 UI: 20155615

"Evidence is increasing that mitochondrial dysfunction is involved in amyotrophic lateral sclerosis... To study the role of mitochondrial dysfunction in the pathways leading to motoneuron death, we developed an in vitro model of chronic motoneuron toxicity, based on malonate-induced inhibition of complex II in the mitochondrial electron transport chain. Treatment with malonate resulted in a dose-dependent decrease in cellular ATP levels [see Creatine ]. We observed that motoneurons were significantly more vulnerable to mitochondrial inhibition than control neurons in the dorsal horn. We could reproduce this dose-dependent phenomenon with the complex IV inhibitor sodium azide. The free radical scavenger alpha-phenyl-N-tert-butylnitrone, the AMPA/kainate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione, and riluzole, a drug that is currently used for the treatment of amyotrophic lateral sclerosis, were protective against malonate-induced motoneuron death. Furthermore, the caspase inhibitors N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone and z-Asp-Glu-Val-Asp-fluoromethyl ketone were both protective against malonate toxicity. Our model shows that chronic mitochondrial inhibition leads to selective motoneuron death, which is most likely apoptotic.


* * *

Much of the ALS mitochondrial work comes from Japan. A good review is: Y Masui, T Mozai and K Kakehi. Journal of Neurology 232:15-19 (1985). Also in English is Nakano et al. Arch Neurol 44:103 (1987). There are other papers in Japanese, with English abstracts: Araki, H. No To Shinkei 30(10):1070-81 (1978) ... and Hirayama, K. No To Shinkei 34(1):33-38 (1982)".



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Contribited by Gayle Eversol:
Excess CHON, especially that from animal protein, can be difficult for the body to excrete properly. This causes an "excess acid load" which leads to overtaxing the liver, sick kidneys (mainly renal tubule failure and other decreased kidney function), decreased muscle mass, decreased hormonal function, osteoporosis, and premature aging. It is also important to note that very low fat diets can cause a build up of toxins in the organs, and additional stressors to organ function. Balance is the key! Fruits and vegetables for CO3(carbonate) provides alkalinity and reduces to CO2 and H2O.

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WATER If ALS/MND is triggered by excessive free radical activity or toxic substances in the body it is essential that you drink sufficient water to aid the liver and kidneys to "flush" these from your body. Tea, coffee and alcohol act as diuretics and can promote dehydration if used in excess. Fruit juices can assist with hydration but plain water is even better. You should drink a minimum of ten 15fl oz/400ml glasses of water per day in addition to other fluids. Some doctors and naturopaths recommend an even higher water intake based on bodyweight (it is medically accepted that 2.5 litres of fluid per day is the recommended minimum intake for adequate metabolic function) but exact therapeutic recommendations vary. If you find it difficult to drink a full glass of water drink smaller amounts but do so frequently. Drink before you feel thirsty if possible.

Drink tea/coffee, carbonated soft drinks, milk and particularly alcohol as "treats" rather than as your primary fluid sources. Numerous studies, particularly in the field of sports medicine, stress the importance of adequate fluid intake and suggest plain water is best. If, as I suspect, liver function is implicated in the rate at which ALS/MND progresses the more plain water you drink the easier it will be for your liver and kidneys to function adequately.

Our bodies contain and average of 40 litres/9.5 gallons of water - Blood = 92% water, Muscle = 80% water, Overall bodyweight is 60%water.

[I now drink a minimum of ten glasses (approx 4 litres/9 pints) of filtered water daily and my consumption (and any craving) for other fluids is minimal. (I had a history of drinking both tea and coffee to excess and these were once my primary sources of fluid each day). I do not crave tea or coffee now but do not deprive myself of either if I feel like drinking them. 4 litres/9 pints may sound like a lot of water and I admit that I struggled to drink this amount for the first four days. Now it feels perfectly normal and I comfortably drink even more on hot days. A frequent need to urinate was a problem for the first week or so but this has now settled to what I would consider "normal" for me.]

There is a book on the benefits of hydration called "Your Body's Many Cries for Water" by Dr. F. Batmanghelidj, a London educated Iranian doctor. I have not read this book (nor do I know the publisher's name) but have sighted a favourable review in Borderlands - A Quarterly Journal of Borderland Research Vol LIII, Number 1, First Quarter 1997.



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"Excitotoxins" by Russell Blaylock, M.D. has been recommended as an excellent book to read for information on how the body responds to toxins introduced into or manufactured by the body. There is quite an extensive portion on ALS and the correlation between MSG and ALS. Cost is is $16.95US. I would also recommend the Herbal Medicine page by Gayle Eversol at http://members.delphi.com/jaspy1/index.html . Gayle Eversol has worked extensively with patients suffering Liver Dysfunction.
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* It is interesting to note that research in 2002 revealed that "Gastrointestinal motor dysfunction can occur in amyotrophic lateral sclerosis, even if patients do not complain of gastrointestinal symptoms. New techniques in non-invasive evaluation of gastrointestinal function showed delayed gastric emptying and delayed colonic transit times in patients with ALS". This could place immense pressure on normal liver function. See: http://www.als-tdf.org/alstdf/research/ ... rticle=728



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REFERENCES

The articles listed below should be available through Medline. Click here to search Medline. You will need to enter Author(s), Journal, date and volume number (if available) to find each article.

(1) Grilli, et al "Neuroprotection of Aspirin & Sodium Salicylate" : Science, 22 Nov 1996, v274.
(2) A Eisen "Therapeutic Opportunities in ALS": The Neurologist, March 1996
(3) Pincus J H. "Folic Acid Deficiency:" Folic Acid in Neurology, Psychiatry and Internal Medicine NY Raven Press 1979
(4) Baker A B. Treatment of paralysis agitans with vitamin B6 (pyridoxine hydrochloride). JAMA 116:2487-7, 1974
(5) Spies T D et al JAMA 115(4):292-97, 1940
(6) Lindenbaum et al NEJ Med 318:1720-28.1988
(7) J Am Coll Nutr 6(5):442.1987
(8) Spies TD, Vilter RW. South Med J 33:663,1940
(9) Rosenberger AI, Med Rec 154:97-100,1941
(10) Reading CM, J Aust Coll of Nutrit & Env Med, Dec 1997



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I would like to thank Mr Stephen Webster of
Nature's Sunshine Products of Australia
for supplying herbs and supplements included in my study
and also the company's consultant Naturopath Mr Jeffrey Wilson
for his assistance in providing reference material.

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