Unfolded Protein Response and A Possible Treatment for CFS

dannybex

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@dannybex

If you had light-colored stools then this could mean that you had Liver / Cholestasis issues. If possible, talk to your Doctor to get a Total Bile Acids test and a Fibroscan.
@mariovitali -- yes, definitely had very pale stools for years. I'm pretty sure I have cholestasis issues, but haven't had a total bile acids test or a fibroscan. I'll google those for more info, thanks.
 

Wayne

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I've been finally able to increase eggs -- couldn't tolerate them for 10 years -- and eggs are a rich, natural source of choline.
Hey @dannybex, in the past year I've gotten into eating raw egg yolks, and discarding most of the whites. I like putting a couple of egg yolks in a large cup of bone broth, and find it to be one of my favorite "comfort" foods, as it has quite a calming effect on my entire system. I probably have this every other day or so. -- All the Best!
 

Eastman

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I have non-alcoholic fatty liver disease...any advice on how to treat our livers naturally? not a fan of milk thistle (too fast of detox for me not happy camper)
The following paper concluded that "adherence to a MedDiet supplemented with certain bioactive compounds and combined with physical exercise may help in the management of liver disease".

Mediterranean Diet and Multi-Ingredient-Based Interventions for the Management of Non-Alcoholic Fatty Liver Disease
And more details on the benefits of olive oil in particular for the liver:

Liver Protective Effects of Extra Virgin Olive Oil: Interaction between Its Chemical Composition and the Cell-signaling Pathways Involved in Protection.

Abstract
BACKGROUND AND OBJECTIVE:
The liver is an organ susceptible to a multitude of injuries that causes liver damage, like steatosis, non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and ischemia-reperfusion injury. Extra virgin olive oil (EVOO), presents several protective effects on the liver, reducing hepatic steatosis, hepatocyte ballooning, fibrogenesis, preventing lipid peroxidation, among other effects. Due to its high levels of monounsaturated fatty acids, mainly oleic acid and phenolic compounds, such as hydroxytyrosol and oleuropein, EVOO is able to participate in the activation of different signaling pathways in the hepatocytes involved in the prevention of inflammation, oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and insulin resistance, allowing the prevention or resolution of liver damage. The aim of this work is to offer an update of the molecular effects of EVOO in the liver and its protective properties to prevent the establishment of liver damage through the regulation of different cell-signaling pathways.

METHODS:
Searches that considered the effects of EVOO in in vivo and in vitro models, whith emphasis in the molecular mechanism of liver tissue damage and prevention and/or treatment of steatosis, steatohepatitis, cirrhosis, hepatocellular carcinoma, and ischemia-reperfusion injury.

CONCLUSION:
The most relevant molecular effects of EVOO involved in the prevention or resolution of liver damage are: (i) Activation of the nuclear transcription factor erythroid-derived 2-like 2 (Nfr2), inducing the cellular antioxidant response; (ii) Inactivation of the nuclear transcription factor-κB (NF- κB), preventing the cellular inflammatory response; and (iii) Inhibition of the PERK pathway, preventing endoplasmic reticulum stress, autophagy, and lipogenic response.
Olive leaf extract in high doses, though, has been found to induce undesirable changes in rodents.

High doses of olive leaf extract induce liver changes in mice

Toxicity of Olive Leaves (Olea europaea L.) In Wistar Albino Rats
 

xrayspex

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thanks--yea I love olive oil and vinegar on my salads
olive leaf extract on the other hand always felt like cr*p after trying that stuff in years past, decided a big NoPe on that one


Liver Protective Effects of Extra Virgin Olive Oil: Interaction between Its Chemical Composition and the Cell-signaling Pathways Involved in Protection.



Olive leaf extract in high doses, though, has been found to induce undesirable changes in rodents.

High doses of olive leaf extract induce liver changes in mice

Toxicity of Olive Leaves (Olea europaea L.) In Wistar Albino Rats[/QUOTE]
 

debored13

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@Gondwanaland, Articles of Ray Peat and present time forums for Ray Peat type information do advocate calcium as being everything, but I think there has been a big shift in "Ray Peat" information. I started reading Ray Peat many years ago and back in the beginning Ray Peat recommended magnesium way way more than calcium. Someone bought his website and is rewriting his articles. The people who run the forums in his name are not giving you true Ray Peat information.

Ray Peat did always recommend drinking orange juice and even eating ice cream, but he always recommended magnesium as a supplement. And magnesium is a calcium channel blocker, which helps the calcium go where it's supposed to go but not where it's not supposed to go.

Although when you think about calcium issues, it's not really the calcium, it's calcium metabolism. So if K2 is causing pain, it might be doing so because of it's power on calcium, but only calcium that is where it's not supposed to be or bound to something it's not supposed to be bound to. For it to be causing pain is very out of the ordinary, though, so the problem seems rather complicated.

I'm not saying magnesium is the answer, or that your husband doesn't need calcium, though. I truly don't know about that. I wonder if adding sodium bicarbonate to his orange juice might relieve the IBS-D, though.
Where did you hear the bolded?? it would be quite surprising to me if that was true!
 

Gondwanaland

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339475/
Korean J Intern Med. 2017 Mar; 32(2): 213–228.
Published online 2017 Feb 8. doi: 10.3904/kjim.2016.268
PMCID: PMC5339475
PMID: 28171717
Reversal of liver cirrhosis: current evidence and expectations
Young Kul Jung and Hyung Joon Yim
Author information ► Article notes ► Copyright and License information ► Disclaimer
This article has been cited by other articles in PMC.

Go to:
Abstract

In the past, liver cirrhosis was considered an irreversible phenomenon. However, many experimental data have provided evidence of the reversibility of liver fibrosis. Moreover, multiple clinical studies have also shown regression of fibrosis and reversal of cirrhosis on repeated biopsy samples. As various etiologies are associated with liver fibrosis via integrated signaling pathways, a comprehensive understanding of the pathobiology of hepatic fibrogenesis is critical for improving clinical outcomes. Hepatic stellate cells play a central role in hepatic fibrogenesis upon their activation from a quiescent state. Collagen and other extracellular material components from activated hepatic stellate cells are deposited on, and damage, the liver parenchyma and vascular structures. Hence, inactivation of hepatic stellate cells can lead to enhancement of fibrolytic activity and could be a potential target of antifibrotic therapy. In this regard, continued efforts have been made to develop better treatments for underlying liver diseases and antifibrotic agents in multiple clinical and therapeutic trials; the best results may be expected with the integration of such evidence. In this article, we present the underlying mechanisms of fibrosis, current experimental and clinical evidence of the reversibility of liver fibrosis/cirrhosis, and new agents with therapeutic potential for liver fibrosis.
Responses during systemic inflammation and intestinal dysbiosis
During systemic inflammation, the immune response is initiated when bacteria are introduced through portal flow from the intestinal lumen. Pathogen-associated molecular patterns (PAMPs) from enteric bacterial organisms and damage-associated molecular patterns (DAMPs) originating from the host tissue upon injury stimulate innate immune cells [40]. Immune recognition of bacteria and PAMPs including LPS, lipopeptides, glycopolymers, flagellin, and bacterial DNA occurs both locally in the gut-associated lymph node tissue (GALT) and in mesenteric lymph nodes (MLN) as well as systemically [41]. Furthermore, immune cells already activated in the GALT and MLN may enter the peripheral blood and spread the inflammatory response systemically. DAMPs and sterile particulates, also released from necrotic hepatocytes, might also contribute to elicit an inflammatory response and fibrosis [42].
Primary biliary cirrhosis
The only clinically approved medical treatment for primary biliary cirrhosis (PBC) is ursodeoxycholic acid (UDCA) [110,111]. However, there are controversies regarding the interpretation of current evidence. In several studies with crossover from placebo or no UDCA treatment, the crossover patients’ conditions deteriorated despite using UDCA [112]. A Cochrane Review evaluating 16 RCTs using UDCA versus placebo revealed that almost half of these trials had a high risk of bias and concluded that UDCA did not significantly improve liver histology and had no demonstrable effect on improving mortality [113]. Nevertheless, UDCA may have benefits in early stage and asymptomatic PBC. In the asymptomatic PBC cohort described by Prince et al. [114], 45% of the patients taking UDCA did not develop liver-related symptoms during a median follow-up of 7.4 years.

The role of immunosuppressive agents in PBC remains controversial. A few studies evaluating methotrexate have presented conflicting results and some studies suggest that methotrexate may worsen mortality [115].

Obeticholic acid, a derivative of chenodeoxycholic acid, has, unlike UDCA, strong activating effects on the nuclear receptor farnesoid X receptor in phase II results [116]. In a recent clinical trial with obeticholic acid as therapy for PBC, favorable effects were also observed in PBC patients with an inadequate response to UDCA [117]. Alkaline phosphatase, γ glutamyl transpeptidase, and alanine aminotransferase levels were significantly improved in patients receiving obeticholic acid compared with those in the placebo group. In this study, the treatment period was only 3 months and liver biopsies were not obtained to identify histologic changes. Subjects were allowed to participate in an open-label extension trial, which demonstrated sustained decreases in liver enzyme levels over 12 months [117]. Future trials to determine the beneficial effects of obeticholic acid on hepatic fibrosis in patients with primary cirrhosis are warranted.
 

debored13

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Hey @dannybex, in the past year I've gotten into eating raw egg yolks, and discarding most of the whites. I like putting a couple of egg yolks in a large cup of bone broth, and find it to be one of my favorite "comfort" foods, as it has quite a calming effect on my entire system. I probably have this every other day or so. -- All the Best!
haha wayne this is such a ray peat thing to do. But yeah I've been very, very ill recently and the thing I tolerate the best is eggs with potatoes, but especially the yolks, which are easier to digest. it's high quality protein and vitamins and very digestible
 

Violeta

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Where did you hear the bolded?? it would be quite surprising to me if that was true!
I used to read at one of the Ray Peat forums. I had been reading Peat's papers forever and noticed a huge difference in the type of writing in the newer articles and brought up the subject. Someone there confirmed they were being written by someone else and that the site had been sold.
 

Malea

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I‘ve got a question: If I remember it right I read somewhere in this thread that in @mariovitali ‘s theory taking p450-inhibitors would be not good.

Now I was wondering if medications that are metabolised through the p450-cytochromes are automatically inhibitors? (For example the betablocker propranolol or many antibiotics)
 
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I would still like to try UDCA/TUDCA but my doctor will never prescribe it as he easily dismissed my pale stools as "absolutely normal" phenomenon. Does anyone know where can I buy a good UDCA without prescription?
I would like to start with UDCA rather TUDCA as taking taurine alone not only doesn't help but makes some symptoms worse(including the pale stools and varicose veins).
 
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I would still like to try UDCA/TUDCA but my doctor will never prescribe it as he easily dismissed my pale stools as "absolutely normal" phenomenon. Does anyone know where can I buy a good UDCA without prescription?
I would like to start with UDCA rather TUDCA as taking taurine alone not only doesn't help but makes some symptoms worse(including the pale stools and varicose veins).
I found several sources for UDCA:

https://www.mimaki-family-japan.com/item/list?keyword_pc=Ursodeoxycholic+acid&x=0&y=0

http://www.buypharma1.com/Products/search/?keyword=Ursodeoxycholic+acid

brandmedicines.com

goldpharma.cn

I've ordered from all of these pharmacies before and can vouch for them.
 
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Is UDCA preferred over tudca
I don't know. The poster was asking specifically for UDCA rather than TUDCA, which is available as a supplement.

Interesting thing about TUDCA. It's found naturally in large amounts in bear bile, and Asian bears have a lot more than American bears. Bear gallbladders have been used in traditional oriental medicine for millennia. I'm Korean, and my parents said that when they were growing up in Korea, bear gallbladder was known as a panacea and was one of the most expensive medicines.
 
Although Ive seen positive effects in my gut irritation and some kind of anxiety lowering effect from UDCA, I´ve noticed it has increased some nasty overgrowths. This hypothesis made sense after readig this :
"UDCA increased mortality of mice following Escherichia coli infection due to the worsening of infection". Seems it lowers lymphocites so those of us with poor inmune funcion should be careful with it.

I´ve also noticed increased fatigue while on it. Has anybody experienced something similar?



Glucocorticoid receptor-dependent immunomodulatory effect of ursodeoxycholic acid on liver lymphocytes in micehttps://www.physiology.org/doi/full/10.1152/ajpgi.00205.2012