the MS liver

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the MS liver

Postby jimmylegs » Sun Mar 15, 2009 1:47 pm

so, cheer and i made a date to talk ms and the liver. i don't know much about the liver yet, but here's a start:

the liver has many functions that are relevant to ms-ers.
i've looked at a few things w.r.t nutrition that involve the liver, such as d3 and uric acid for starters. i've been looking at zinc and the liver for a while, and the relationship between zinc and uric acid status.

i've posted quite a bit about zinc deficiency causing membrane (keyword: endothelial) permeability problems (intestinal wall, blood brain barrier, optic neuritis, veins, etc etc etc) that are familiar to your average ms patient.
cheer mentioned a case earlier today, where a liver transplant caused a major EDSS improvement in an ms case.

today i got onto the idea of zinc deficiency potentially causing damage to the liver itself, so i searched for liver enzymes and zinc deficiency on google with this interesting result:

Effect of low-zinc status and essential fatty acids deficiency on the activities of aspartate aminotransferase and alanine aminotransferase in liver and serum of albino rats
Abstract
The effects of dietary deficiencies of zinc and essential fatty acids (EFAs) or both on aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were investigated in young growing rats. Four groups of albino rats were fed diets deficient in either EFA (4% hydrogenated coconut oil) or zinc (6 ppm) or both. The control diet was adequate in EFA (4% soybean oil) and zinc (100 ppm). The feeding trial lasted eight weeks and the activities of AST and ALT were determined in the liver and serum. EFA deficiency had no significant (p > 0.05) effect on liver AST. However, zinc and the double deficiencies depressed AST activity in the organ. Deficiencies of EFA, zinc and their combination depressed ALT activity in the liver significantly (p < 0.05) with a concomitant increase recorded in the serum. The data suggested alteration in endothelial permeability of the plasma membrane and thus leakage of membrane constituents in the tissue studied. It is therefore considered that these deficient diets may affect liver tissue negatively in view of the role of these enzymes in amino acid metabolism.


what happens in amino acid metabolism? ammonia gets produced. it's the liver's job to detoxify said ammonia. ideally, it does this by converting the ammonia to uric acid. in which we know ms-ers are dramatically low.
http://users.rcn.com/jkimball.ma.ultran ... Cycle.html
the liver requires zinc to get the job done. and/or, apparently, EFA.
Several studies have shown that zinc plays a regulatory action on the activity of ornithine-transcarbamylase (OTC), a key enzyme of urea cycle.


thoughts/comments?
my approach: no meds so far - just nutrient-dense anti-inflammatory whole foods, and supplements where needed
info: www.whfoods.com, www.nutritiondata.com
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Postby cheerleader » Sun Mar 15, 2009 4:23 pm

Thanks for starting the liver party, Jimmy.
Interesting to see how zinc deficiency can manifest in the liver. Makes sense...since permeability would allow for the enzymes to enter the blood stream.

I started looking into the liver connection and MS was because of my husband's first MS flare. He presented with 10x normal AST and ALT enzymes. This was before any steroids or medications, which might have created damage. He was jaundiced, and I asked his neuro why. She replied that he needed to stop drinking. Since I'm married to a non-drinker, I told her that was not the cause. She rolled her eyes. I got angry, and began my search.

Now with the chronic venous insufficiency research of Zamboni, I find myself returning to the liver connection. If venous problems are implied in cerebrospinal area, they could also manifest in the hepatic system. Afterall, it's all the same body- even if it takes seven different doctors to treat it.

High liver enzymes signal liver damage- when liver cells are damaged, they leak enzymes into the blood stream. The liver is also implicated in coagulation issues. I believe the link between liver health and MS has not been pursued, due to many factors- specifically the highly specialized medical profession

Back in 1854, Friedrich Theodor von Frerichs, a generalist and physician, wrote about connections he found between the liver and the brain and disease in both due to copper metabolism- Now known as Wilson's disease-

This interesting paper discusses the history of the connection between brain and liver
The Neurology of Liver Failure

Many patients with chronic liver disease also complain of fatigue, and the mechanisms of this symptom are poorly understood. It would seem unlikely to have a single cause, but may be due in part to altered central neurotransmission involving the serotonergic system.2 Fatigue is a common complaint in many medical and psychiatric conditions. It is particularly common in neurological disorders such as multiple sclerosis, and the mechanisms involved may be similar.

http://qjmed.oxfordjournals.org/cgi/con ... l/96/9/623

Here is the study which first caught my eye-
http://www.neurology.org/cgi/content/abstract/67/7/1291

The risk of an abnormal liver test in 813 patients with multiple sclerosis or clinically isolated syndrome enrolled in placebo arms of clinical trials was greater than expected for alanine aminotransferase (ALT) (relative risk [RR] 3.7; 95% CI: 2.3 to 6.0) and aspartate aminotransferase (AST) (RR 2.2; 95% CI: 1.3 to 3.6), although not alkaline phosphatase (AP) or total bilirubin, at first presentation. Abnormal test results were associated with higher body mass index (ALT only), male gender (ALT only), and a relapsing-remitting (vs secondary-progressive) course (ALT and AST only).


Currently, all MS patients on drugs are routinely tested for elevated liver enzymes, because it is assumed that the high numbers of liver problems associated with these treatments are created by the medications. What if, as the above placebo arm of clinical trials indicated...liver damage is NOT related to the treatments, but exists in the MS patient, whether or not they are on a specific medicine.

Why is this not being further researched? Bring me your liver insights!

AC
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby jimmylegs » Sun Mar 15, 2009 4:48 pm

it's weird, i got some baseline liver enzyme tests early on, when i was still considering pharmaceutical options. i didn't know much back then about being critical of the "normal range" idea, but as far as i know my enzymes were normal. wish i had had a liver enzyme test around the time of that zinc test with the major 8.6 deficiency!

cheer, what do you think caused jeff's liver damage? have you guys done a history/systems analysis?
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Postby cheerleader » Sun Mar 15, 2009 5:11 pm

Hey Jimmy-
Have you done the whole history/systems analysis? Did you find a good doc?
We've never pursued it since I haven't found a doc interested in anything outside their specialty. Even our GP likes to keep it to blood tests, blood pressure and a prostate check. Jeff's enzymes resolved after beginning milk thistle and his supplements/diet and haven't been a problem since.

When he was diagnosed, he had a lumbar puncture and his spinal fluid was tested for everything- viruses, bacteria- which may have been implicated, but all was negative. We found no reason there for the elevation in liver enzymes...but he showed bands, so as far as his neuro was concerned, it was case closed. Simply MS.

In researching the endothelium, I learned how so many factors- vitamin deficiencies, toxins, stress- can break down blood vessel walls. I began looking at his MS more holistically. The high liver enzymes from his first flare were maybe a sign of a system in breakdown.

Now in researching venous insufficiency, I'm learning how the hepatic system can suffer due to venous obstruction. I'm just thinking...if the veins can be blocked in the brain/spine- why not the whole body?
AC
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby jimmylegs » Sun Mar 15, 2009 6:55 pm

hi cheer figuring out how i had done this to myself was about all i did for the first 6 months! still learning years later, but the curve was the steepest in those first 6 months. that's all i meant by system analysis. a big kind of in-out diagram. i still have mine, found it the other day. after 3 years of reading i would probably do it up a little differently but it's still pretty close to the mark i think.
i don't think my doc's much diff than yours - i just get bloodwork and mris.
of the original medical crew, most of them i only saw once or twice. my gp and neuro and two pharmacists are the long term crew.
those stupid o-bands. grr.
jeff has some bloodwork coming up does he not? what are you guys monitoring (i know you know zinc = 18.2 ;) )
yes i agree, all the various weakened membranes probably have system-wide implications.
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Postby jimmylegs » Wed Mar 18, 2009 10:49 am

skydog here it is. fire away.
my approach: no meds so far - just nutrient-dense anti-inflammatory whole foods, and supplements where needed
info: www.whfoods.com, www.nutritiondata.com
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Postby skydog » Wed Mar 18, 2009 12:13 pm

Thank you !!! Legs I am on it now... Too hot at high noon here to work out side so time for research... M
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Postby skydog » Fri Mar 20, 2009 5:15 pm

Liver Health

Friday, March 20, 2009
1:24 PM

Ah the liver. It seems I am just scratching the surface on how important this most vital organ is to our health. I also was asked if I was a drinker by my naturopath. I was astonished to find that my liver enzymes were so high. Why so high when I do not consume processed foods, take any of the disease modifying drugs, drink very little alcohol, and only an occasional pain med. I eat home grown organic vegetables, grass fed or wild meats, and consume very little alcoholic beverages. There must be another connection. Could the stress put on the system from MS be the reason ? It does seem likely. So since we have to live with our MS for now its obvious that helping the liver function to its fullest is paramount to our health.
Now to achieve a healthy liver for many may prove difficult because of lifestyle and certain drugs. My personal approach is to continue to eat raw enzyme rich raw foods and take a good probiotic keeping the digestive system working smooth. Eat less !!! Quality over quantity. Everything we eat has to be processed by our liver then stored or used by our body.
Our symbiotic body does not require large amounts of food once the body has an abundance of the aerobic bacteria. Lots of time and money is saved by not having to eat as much. Breakfast first thing in the morning is not what we think is good. The body is eliminating the toxins in the body that take place in the morning when we awake. I believe that fasting until lunchtime will prolong life. Remember, we are eating for hunger, not addiction.

Pasted from <http://blindguru.com/symbiotic_eating.html>
Build a healthy gut flora that aids in fully using foods we consume to power up the liver.
Your nerve sheath (myelin) is about 80% fat.
Every nerve ending in your body has a  fat sheath.
Consumption of strange undigestable proteins and runaway sugars may be among the causes of most disease.
Excess protons producing an acidic/mycotoxic bio-terrain are conducive to bacterial growth.
Sunlight provides critical stimulation to various endocrine organs and areas within our brain.
Years of fermentation may not break down many of the strange undigestable proteins found in modern food,  nor may they ever be within your body.
Consumption of strange undigestable substances may cause the production of endorphins (endogenous morphine-like substances) resulting in misplaced attraction.
Strange undigestable proteins that irritate the delicate linings of the digestive tract may cause extra salivation and unnatural craving for poor food choices.
We should not have bacteria within the interior of our body; rather we are designed to host extensive bacterial colonization on our exterior membranes.
Unfriendly bacteria are able to propel themselves throughout the interior of the body causing problems.
Unwanted body mass may be composed of at least the following: water, fibrin, mucous, globulin, calcification or fat.
If average, you may have about sixteen pounds or two gallons of excess mucous distributed throughout your body.
The increase in chronic diseases suggests much of our immunity and healing currents have been lost due to a molecular and informational environment hostile to our essential biological partners-body flora.
Perfect body ecology is achieveable without diet revision, tasteless food, excessive raw food or exercise.
Many of us have experienced periods of prolonged unexplainable fatigue and malaise. 

There appear to be a lot of sick and tired people.
Our adrenal glands are involved in many physiological processes such as regulation of sugar, inflammation, sexual, immune and stress response.
Cortisol  (death hormone) appears to work together with insulin since cortisol levels rise as we prepare to release glucose for energy.
When cortisol levels are high and glucose is released for long periods of time, we may convert some of the extra glucose to fat.
Circulation of runaway sugars encourages the acidic bio-terrain giving rise to a dysbiotic unhealthy life cycle.
Storage fat often accumulates around the abdomen, hips and thighs as the fat cells in these areas possess five times as many cortisol receptors as other fat cells.

Pasted from <http://blindguru.com/symbiotic_quotes_and_pictures.html>
Effortless, deep, undisturbed and rejuvenating sleep can be expected with perfect body ecology.
Precious element such as gold, platinum, palladium and silver may provide superior conductivity within your brain and myelin resulting in the readiness potential of your nerve system.
Flexibility and a spacious feeling in the joints is likely to result from perfect body ecology.
Twenty-two amino acids arrange in various combinations creating over 100,000 unique proteins which compose your body.
Your body may be thought of as a community of about 50 trillion cells.
Your body has about 200 billion nerve endings half of which are within your brain.
Panoramic enhanced depth perception followed by a singular eye visual sense is possible with perfect body ecology.
Once body ecology has been perfected, you may permanently host as many as 5,000 trillion friendly microscopic partners (body flora) residing mostly within your digestive tract.

Pasted from <http://blindguru.com/symbiotic_quotes_and_pictures.html>
The more I look into what constitutes a healthy liver the more I realize that the a healthy digestive system is the first step in that process. We cannot possibly create what our liver does naturally by consuming a mass quantity unnatural drugs and supplements. Some supplements will however aid us when certain conditions leave us deficient. The goal is to balance our needs to assist the body in doing what it likes to do naturally. Peace and Health Mark PS It is my hope that many of you will take the time to read some of the text presented on the blindguru site. Keep an open mind and healthy body. A special thanks to Legs and Cheer your research efforts are greatly appreciated.
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Myelin on nerves

Postby lyndacarol » Fri Mar 20, 2009 5:51 pm

Skydog--you posted,
Every nerve ending in your body has a fat sheath.
Even on the optic nerve?

I think I have read that the optic nerve is NOT covered with myelin.
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Postby jimmylegs » Fri Mar 20, 2009 9:16 pm

i don't agree with all of these, and some other aspects of liver health are absent - but this is kind of cute:

15 ways to love your liver
http://www.doctoryourself.com/liver_15_ways.html
my approach: no meds so far - just nutrient-dense anti-inflammatory whole foods, and supplements where needed
info: www.whfoods.com, www.nutritiondata.com
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Postby cheerleader » Fri Mar 20, 2009 10:02 pm

Mark-
Thanks for the info from the blind guru...very informative.

So, you had high liver enzymes, too?!? Have you had them checked recently, have they resolved? My husband's have been OK on his new regimen, which includes milk thistle, healthy fats, lots of D and B12, and zinc. And he still doesn't drink.

I'm fascinated with the correlation of liver disfunction in MS patients...and still stymied as to why this is overlooked by docs. I'm also wondering if it is more prevalent in males with MS. From the study cited above-
Abnormal test results were associated with higher body mass index (ALT only), male gender (ALT only), and a relapsing-remitting (vs secondary-progressive) course (ALT and AST only).


Why??? Could it be problems with stored iron, as found in hemochromotosis? Males' higher body mass would mean more iron and men don't menstruate and get rid of blood that way...Iron overload can be a reason for high AST and ALT #s.

Like the 15 ways to leave, I mean love, your liver JL. I'll be singing that around the house.
AC
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby skydog » Fri Mar 20, 2009 10:31 pm

Right wrong or indifferent Ya gotta love your liver it is truly a powerhouse for supplying the old body with what it needs. I am going to test my liver function after a couple of months with my new regime. The last one was a couple of months back and still showed slightly elevated enzymes. Now this is an eye opener Retinal venous sheathing in optic neuritis. So much too learn for a simple country boy. Little things that seem to creep up on me these days may have more in common with the ms than simple age related vision loss. Taking my tired eyes to bed... Peace Mark
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Postby jimmylegs » Sat Mar 21, 2009 6:26 am

glad u like that cheer hehe - i still think some of the 15 are better than others tho.

so, iron does inhibit zinc absorption, as does the consumption of phytates in food, which we seem to do more of these days (NZ study but it would seem to apply in 'developed' countries i think) and men do tend to use part of their zinc supply.. regularly... so i imagine to keep the balance in line, good ol' 18.2 would be at least part of the objective :)

gotta tighten up that junction function, across the board:

Zinc deprivation induced a decrease of transepithelial electrical resistance and alterations to tight and adherens junctions...


5) co-treatment with [zinc] protects against the renal toxic effects of [cadmium] preventing altered claudin expression and by inhibition of apoptosis. In conclusion, these results show that [cadmium] toxicity and cellular toxic mechanisms are complex, probably affecting both membrane transporters and tight junction proteins.


Apoptosis plays a causative role in acute lung injury in part due to epithelial cell loss. We recently reported that zinc protects the lung epithelium during inflammatory stress whereas depletion of intracellular zinc enhances extrinsic apoptosis... We hypothesized that exposure to inflammatory cytokines, in conjunction with zinc deprivation, would induce caspase-3, leading to degradation of junction proteins, loss of cell-to-cell contact, and compromised barrier function.


... tight junctions join together the cytoskeletons of adjacent cells... They perform three vital functions:
* They hold cells together
* They block the movement of integral membrane protein
* They prevent the passage of molecules and ions through the space between cells... This pathway provides control over what substances are allowed through. (Tight junctions play this role in maintaining the blood-brain barrier).

great diagram: tight junction - click it!
http://en.wikipedia.org/wiki/File:Cellu ... ion_en.svg
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Postby skydog » Sat Mar 21, 2009 8:11 am

The most common cause of liver damage is malnutrition. The best treatment is a wide varied diet. Plant a bigger garden. M 5) co-treatment with [zinc] protects against the renal toxic effects of [cadmium] preventing altered claudin expression and by inhibition of apoptosis. In conclusion, these results show that [cadmium] toxicity and cellular toxic mechanisms are complex, probably affecting both membrane transporters and tight junction proteins. Interesting had some blood work done to test for heavy metals. My mercury and cadmium were off the chart. Eating lots of cilantro in season and drinking chlorella periodically in the winter.Oh and now supplementing with zinc... Thanks to jimmylegs M
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Postby mrhodes40 » Sat Mar 21, 2009 9:09 am

I am not trying to be a pain but just want to say my liver enzymes have always been absolutely super fine. Good kidney function too. Even when I take things that challenge them, they stay OK. I've been on MTX (low dose chemo), hydroxychloroquine, high does NSAIDs, baclofen, antibiotics in various combinations (doxycycline, minocin, azithromycin, clarithromycin, flagyl, tinizadole), fluconazole, and copaxone.

In my particular case I have always seemed by and large healthy with nothing on test after test. When we were originally trying to get me diagnosed it was frustating that eveything came back normal all the time.........of course until we got to the MRI and saw lesions or tested for rheumatoid, finally showing MS and RA both.

I wonder how common it is for the profile that Cheers husband and Skydog had to exist in MSers wherein there is some obvious liver issues?
I see the study you poste cheer but does everyone's neuro check liver stuff? or even ask if your primary has checked recently?

But from the "chlamydia pneumoniae" world, CPn loves to live in liver cells and screw up the liver, just food for thought. This is one reason abx treatment may mess with yout liver enzymes: liver cells are being targeted and abx induces apoptosis in those infected
http://www.ncbi.nlm.nih.gov/pubmed/15239615
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