Gauf - SAMe study

Gauf thought you might find this study interesting. Its being done in Switzerland.
AdoMet is another name for SAMe. Anyone know what Betaine is.

This so agrees with the way I think on Non response, so I hope it works.

http://clinicaltrial.gov/ct2/show/NCT00310336?cond=%22Hepatitis+C%2C+Chronic%22&rank=182

S-Adenosylmethionine and betaine correct hepatitis C virus induced inhibition of interferon signaling in vitro.

Duong FH, Christen V, Filipowicz M, Heim MH.

Department of Research and Division of Gastroenterology and Hepatology, University Hospital Basel, Switzerland.

Hepatitis C virus (HCV) infection is an important cause of chronic liver disease. Standard therapy, pegylated interferon alpha (pegIFNalpha) combined with ribavirin, results in a sustained response rate in approximately half of patients. The cause of treatment failure in the other half of the patients is unknown, but viral interference with IFNalpha signal transduction through the Jak-STAT pathway might be an important factor. We have shown previously that the expression of HCV proteins leads to an impairment of Jak-STAT signaling because of an inhibition of STAT1 methylation. Unmethylated STAT1 is less active because it can be bound and inactivated by its inhibitor, protein inhibitor of activated STAT1 (PIAS1). We show that treating cells with S-adenosyl-L-methionine (AdoMet) and betaine could restore STAT1 methylation and improve IFNalpha signaling. Furthermore, the antiviral effect of IFNalpha in cell culture could be significantly enhanced by the addition of AdoMet and betaine. In conclusion, we propose that the addition of these drugs to the standard therapy of patients with chronic hepatitis C could overcome treatment resistance.

CS

[gauf]

Wow!  I am soooo glad I had to postpone treatment as it seems so much is coming in to help the odds of a successful plan. You know anything about Germanium GE1-23 ? Wondering if lowering the VL prior to tx with this is a good idea. If it simply mimics interferon though, then maybe it is a waste of time.  I will look into adding sam-e to the supplement list especially now that we have a study! Wish HR was around.

Thanks dude!

[Ginger12521]

Sparrow, thanks for the info! I already take both SAM-e and eat beets like they're going out of style. Beets are a great natural source of Betaine! I also juice them with celery and carrots on a regular basis. Guess I'm going in the right direction.

Gauf, just wanted to say that SAM-e has turned my life around, and I highly recommend it! Normal enzymes (not on tx), and it greatly improved my mild depression I had been dealing with since diagnosed.

Here's an interesting article about Beets. : )

http://ourworld.compuserve.com/homepages/Stephen_Nottingham/beetroot6.htm

[gauf]

I have TMG in my regimen which is also a Methyl Donor so perhaps adding Sam-e is overkill..... and maybe not. Time to do some homework.

[Bobby1952]

I looked at the list in your profile and it shows tmg and sam-e. Does it mean you should take both . I thought it did and I am taking both.Along with ppc and a few other things. Does anyone know if the sam-e is effective without the betaine. Or do we need both. Can someone find out what HR thinks.

Bobby

[gauf]

Perfectly fine to take both. I sometimes wonder about overkill mainly due to the expense. I do not want to take more than I can use and flush out the rest. I hate to waste anything. The dosages in my profile are HRs' recommendations for those with Fibrosis or Cirrhosis. Not sure about the Betaine yet.

[sfbaygirl]

I ordered so many things yesterday, I forget if I ordered this. I have seen SAMe in stores. Is it as good, or is it less on Smartbomb?  

[CockSparrow]

TMG is the precursor to SAMe so taking both may be overkill.
SAMe is more expensive.

Gauf
Looks like adding SAMe to what to take on Tx is worth thinking about even if we are preempting the results of the study.
CS

[Bobby1952]

Guess what? Betaine and TMG are the same thing. Here is an excerpt from the link that ginger posted on Beets.  

Clinical depression is a chronic disease that is very prevalent in industrialized countries. It has been estimated, for example, that up to one in twenty Americans suffer from clinical depression, to the extent that they require some form of treatment. Depression is closely linked to the dysfunction of neurotransmitters in the brain, particularly serotonin. Low levels of serotonin affect a range of physiological processes that result in depression. One approach to treating depression is through diet and dietary supplements. A number of compounds in foods have been shown to raise serotonin levels and induce a subsequent calming effect in patients suffering from depression. Betaine, which is also known as trimethylglycine (TMG), is one of these. Treatment with betaine (TMG) raises levels of a compound called s-adenosylmethionine (SAM), which in turn influences serotonin metabolism.

TMG and SAM are said to be “methyl donors”, because they donate methyl groups to other molecules to facilitate beneficial chemical processes. In addition to neurological effects, betaine acts a methyl donor to affect changes in the cardiovascular system, the liver and other organs.

Betaine is used to treat a genetic condition called homocystinuria. People with this condition have unusually high levels of the amino acid homocysteine (Hcy) in their blood. This chemical can be toxic and it contributes to an increased risk of heart disease and strokes. Betaine supplements, acting with other nutrients, particularly SAM, folic acid and vitamins B6 and B12, break down Hcy and prevent it from reaching toxic levels in the blood. High levels of Hcy can also occur in people without homocystinuria, who have high Hcy in their blood, for example, due to a dietary imbalance. These patients can also be treated with betaine supplements.

Very interesting.....I guess HR does know what he speaks of !!  LOL.  

Bobby

[Hepatitis Researcher]

betaine is just another name for TMg = Trimethylglycine, I have listed here, on this board, all these synonyms in the past to avoid the confusion that sometimes arises from all these different names for the very same thing.

Exactly as CS says above Same is quite expensive, TMG=betaine is cheap. For that reason, very much on purpose i have, considering people on a low budget, only typically  listed the TMG and not the SAme, since TMG can donate its methylgroup to the production of SAMe (S-Adenosyl-Methionine- the activated form of Methionine and therefore the actual donor of Methyl groups in the myriad of critical synthetic metabolic enzymatic reactions that require Methylation).
Nevertheless, if someone can afford it, having extra SAMe supplied directly, without the need to synthesize it from TMG and DMG, might still add extra benefits and will have no neg effects whatsoever (except the extra cost).


To Gauf: Best to not touch Germanium. As a transition type metal element it will have numerous prooxidative toxic effects - that might in some cell types, like macrophages - result in NFKappaB activation with subsequent Interferon production in response to this damage signal. This is not worth the ill defined risk of broad toxicity.

If someone wants to be super complete with respect to covering all nontoxic antifibrotic concepts and approaches, there is one more that I have - again for the purpose of not to confuse and over complicate and dilute the order of priorities - not ever mentioned yet here , since it does require a prescription; It is ursodiol, a bile acid derivative that reduces substantially the inherent stress and toxicity that the bile production burdens the liver with, by enhancing its excretion and reducing the metabolic stress that bile production places on the liver. It is used with great success and routinely in patients with primary biliary cirrhosis, where this mechanism of liver burden and damage is chronically out of control resulting in cirrhosis by itself. But

as an article fairly recently supplied by JIm JIm has AGAIN ( there is lots of previous lit showing small but consistent benefits of ursodiol on all forms of Hepatitis) nicely shown

it is able to reduce ALTS and liver stress in nearly all forms of Hepatitis as expected if one understands the bile production burden/stress on the liver. The problem is, that your hepatologist has to prescribe it to you and you might best achieve this by arming yourself with Jims abstract. If it would also supply benefits while on tx - no clear answer to this question. Now i am hours from departing to NZ and can answer no more questions until middle of march...

[geterdone]

have a safe trip and enjoy.

jasper

[gauf]

Thanks and bring back new and interesting info!

[merryBe]

that's more good news on the preventative front!!!

I think the TMG makes sense on the budget end, but the Sam-e does improve joint function and mental health as well. I noticed an marked joint imptrovement the first week.

HR   when you get back could you tell me why Sam-e is so dangerous with anti- depressants and does this apply to trycylics as well as seretonin uptake inhibitors?

JIM   please can you post the articles mentioned?

GiNGER   I'm a little concerned about your beet intake. Beets are a great source of iron, I know, I used to drink fresh beet juice for that purpose. However, with HCV we can get overladed with iron....So other sources for Betaine would be best.

great thread, thanks to all!!
mary B

[sfbaygirl]

Thanks for the update HR! I also wanted to mention that when I saw HR he mentioned the danger of Grapefruit juice in large quanities. It can cause liver damage, if too much is taken.

[sfbaygirl]

I was just looking at my list of things I ordered yesterday. It looks like I have ordered TMC, not TMG.  Do they ever mention it this way?  It says TMC Biologics....is this a mistake?  

Thanks!  
Linda

[CockSparrow]

Yeh its sounds like you paid $29 for the wrong thing. That is if you ordered Bio-Logics Tmc. No idea what it is though. TMC is an abreiviation for heaps of things!
Heres the page for TMG
http://search.smartbomb.com/?catalog=smartbomb&.autodone=http%3A%2F%2Fstore.yahoo.com%2Fsmartbomb%2F&query=TMG

Bobby - Betaine and TMG are the same thing. Go figure.
Time to put together a list me thinks.
CS

[gauf]

Yup, TMC is the wrong stuff! They don't ship that fast so you can call or e-mail and make the change.  This is the stuff I get. "Source Naturals TMG 750mg (Trimethylglycine) 240 tabs"    1 tab 2x a day.

[sfbaygirl]

Thanks, I got it straightened out. Thankfully, they don't ship too quickly. I paid for TMC 29 bucks, for something I had no clue about!  I switched. I am so used to not checking my spelling much,  I didn't notice. Dumb and dumber here!  I'll get it down after a while. Not used to all this stuff!

[gauf]

Perhaps not on the liver, but studies show it has some benefit in boosting the immune system and helping low platelet counts.

[Ginger12521]

merryBe--
Hi, You bring up a very good point with the beets and iron. I'm aware of the iron issues with HCV and how high ferritin levels may induce liver damage.  I'm so fortunate to have found a great Internist a few years ago who's big into Integrative Medicine. He made me aware of the dangers of high iron and HCV. Mine was a bit low on my last few tests, so I think I'm ok. Also, I should have elaborated on how many beets I eat. "Going out of style" could be interpreted in many ways. In reality, I eat, at most, 1 beet daily...either in juice or cooked.
I've really acquired a taste for them  :)

Here's an interesting article in regards to Insulin resistance and iron...news to me. I don't know if routine liver tests include Ferritin. My Internist always orders this test for me.

Active Low-Carber Forums > Main Low-Carb Diets Forums & Support > Low-Carb Related USENET Newsgroups > Nutrition > Ferritin / iron / insulin / hepatitis
PDA

View Full Version : Ferritin / iron / insulin / hepatiti




Ironjustic
Sun, Nov-06-05, 06:16
Elevated Serum Tumor Necrosis Factor Alpha and Ferritin May
Contribute to the Insulin Resistance Found in HCV Positive
Egyptian Patients

M=2E Elsammak; W. Refai; A. Elsawaf; I. Abdel-Fattah; E. Abd
Elatti; A. Ghazalf

Abstract and Introduction Abstract Objective: There is
evidence of an increased incidence of insulin resistance and
diabetes mellitus (DM) in patients with hepatitis C virus
(HCV) infection. Several mechanisms have been proposed,
including inadequate insulin secretion or interference with
signaling within the insulin receptor. We assessed serum
tumor necrosis factor alpha (TNFa) and ferritin levels as
potential mediators of insulin resistance in HCV positive
Egyptian patients. Patients and Results: Patients ( n =3D 27)
with HCV infection, patients ( n =3D 23) with hepatitis C and
DM (HCV + DM), patients ( n =3D 22) with DM, and sex- and
age-matched controls ( n =3D 18) were included in this study.
The degree of insulin resistance (HOMA index) was
significantly higher in the HCV, HCV + DM and DM groups
compared to the controls. The mean =B1 SD of the HOMA index
was 4.53 =B1 2.84, 6.1 =B1 2.36, 3.69 =B1 2.2 and 1.32 =B1
0.49, in HCV, HCV + DM, DM and controls, respectively. Serum
TNFa levels were significantly higher in the HCV, HCV + DM
groups compared with the healthy controls and DM patients ( p
< 0.001). The median (range) values of TNFa in HCV, HCV + DM,
DM patients and controls subjects were 25.5 (0.43-124.0),
19.8 (0.51-139), 0.85 (-10.5) and 0.32 (0-5.8)pg/mL,
respectively. There was a significant positive correlation
between the HCV load and both HOMA index and TNFa level. HCV
and HCV + DM patients also had significantly higher serum
ferritin levels compared with healthy controls and patients
with DM. The mean =B1 SD of serum ferritin in HCV, HCV + DM,
DM patients and controls subjects was 258.1 =B1 116.2, 285.8
=B1 124.3, 86.9 =B1 41.8 and
159.9 =B1 76.9ng/mL, respectively. Conclusion: Patients with
HCV infection had a significantly higher level of TNFa
and ferritin which may explain their insulin resistance.
HOMA index and serum TNFa levels correlated positively
with the HCV load.

Introduction Evidence showing a higher prevalence of diabetes
mellitus (DM) in patients with chronic hepatitis C virus (HCV)
infection has been accumulating.[1-3] The underlying
mechanisms explaining the connection between HCV and insulin
resistance and the onset of type 2 DM are still unclear.
Several mechanisms have been proposed, including insulin
resistance and inadequate insulin secretion.[4-6] Other
reports suggested that insulin resistance may just be a
consequence of steatosis. Hepatic steatosis is recognized as a
component of the metabolic syndrome and precedes the onset of
type 2 DM.[7-9] It has been suggested that the connection
between hepatitis C and DM could be secondary to the ability
of HCV to induce hepatic steatosis.[7,8] Another possible
explanation is a direct effect of HCV proteins on
insulin-signaling pathways.[10-12]

Tumor necrosis factor alpha (TNFa) induces serine
phosphorylation of IRS-1 (insulin receptor substrate-1) and
thus inhibits its tyrosine phosphorylation and signaling
activity.[12] Defects in the insulin receptor and IRS-1 are
present in insulin resistance and type 2 DM.[13] Furthermore,
the proinflammatory cytokine, TNFa, has the ability to inhibit
insulin-stimulated glucose uptake.[13]

Other factors that could play a role in the development of
insulin resistance and subsequent DM include obesity and high
iron level. Cross-sectional studies suggested that there is a
positive correlation between body iron stores and disease
severity in HCV.[14] Furthermore, the relationship between
iron overload and the development of DM is well
established.[15,16]

To date, few data are available about the relationship between
the HCV load, serum levels of TNFa and ferritin and the
development of insulin resistance. We aimed to investigate the
status of insulin resistance in Egyptian patients with HCV
infection, patients with HCV + DM (HCV + DM) and its
relationship to TNFa and ferritin levels and virus load in
comparison with age- and sex-matched healthy controls and
another control group with DM but without HCV infection.

--------------------------------------------------------------
--------------=
-----

M=2E Elsammak ,a W. Refai ,b A. Elsawaf ,c I. Abdel-Fattah ,d
E. Abd Elatti e and A. Ghazalf f

aDepartment of Chemical Pathology, Medical Research Institute,
Alexandria University, Egypt bDepartment of Gastroenterology,
Medical Research Institute, Alexandria University, Egypt
cDepartment of Physiology, Medical Research Institute,
Alexandria University,Egypt dInternal Medicine Department,
Alexandria Student University Hospital, Egypt eDepartment of
Internal Medicine, Menofeya University, Egypt fDepartment of
Microbiology, Medical Research Institute, Alexandria
University, Egypt

Curr Med Res Opin. 2005; 21 (4): 527-533. =A92005
Librapharm Limited

[Ginger12521]

hi,
I couldn't find the post in which you were asking about the recommended dose of SAM-e. Some studies used up to 1600 mgs daily. I can't imagine taking that much! My purse couldn't imagine it either. :)

On my Alternative HCV group the men mentioned they needed a larger dose to find benefit for relief of depression and body aches. I'm guessing this could be a weight dependant dosing issue. One man took 800 mgs daily for a couple of months and claimed he found great relief from the post tx aches and pains. I weigh 135 and find benefit with just 200 to 400 mgs daily.

I first became interested in SAM-e for antidepressant qualities. Plus, I felt good about the fact it may help with liver disease. Not many Rx's out there that can make that claim!
I use Natures' Made brand....available at many pharmacies.