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Tuesday, 22 January 2013

Fatty liver and its treatment.



Fatty liver (steatosis) is pretty much the precondition of fibrosis, cirrhosis and hepatocellular cancer.

Steatosis and hepatic IR are closely associated but it is still poorly understood whether it is steatosis which causes IR, or vice versa. It is clear however that steatosis and IR usually precede inflammation, fibrosis, and cirrhosis of the liver.

Steatosis is produced experimentally in animals by a) toxins and alcohol – in which case the effect will be made worse by high-PUFA diets, reversed by diets providing highly saturated fats, usually beef tallow or coconut oil, and kept stable by moderately saturated fats such as olive oil and lard, b) high-fat diets (high PUFA) with round-the-clock feeding (but not with feeding in a time-restricted window), c) diets deficient in choline, or in the raw materials needed to make choline; methionine, folate and B12 (however, deficiencies of B12 and folate have other serious effects which might mask their importance in this regard), d) diets deficient in antioxidants that prevent lipid peroxidation, usually selenium and tocopherol.
Up-regulation of
PPAR-alpha is protective against steatohepatitis and inhibits HCV replication.

PPARα was also reported to be down-regulated by HCV in the liver of infected patients [8889]. Since PPARα blocks the replication and production of infectious viral particles, its downregulation likely confers a replicative advantage to the virus in spite of the resulting metabolic disorders for the host cells [9091].

PPAR-alpha is upregulated by intracellular peroxidation of DHA, by carbohydrate restriction, and by fasting, as well as by the flavanone naringenin, an antioxidant found in grapefruit, oranges and tomatoes.

From this we might be able to construct a diet that prevents or reverses fatty liver, and thus prevents its sequellae:

·         The fats in the diet will be highly saturated; beef and lamb dripping, coconut oil, dairy fats and olive oil, but there will also be optimal amounts of DHA from fish and seafood.

·         The diet will supply ample choline, from offal and eggs, and methylation factors B12 and folate from meat and vegetables (spinach and beetroot are excellent sources of the alternative methylation factor betaine). 

·         Carbohydrate will be restricted (and low GI), caloric intake will not be excessive, and round-the-clock feeding will be avoided.

·         The diet will be high in antioxidants. It is important for the activation of PPAR-alpha that DHA peroxidize in hepatocytes and not in the gut or the blood. In this paper vitamin E protects DHA, but I’ve also read that grape seed extract(*) is effective, so we are probably looking at a general antioxidant effect, such as you’d get from a dish like sardines, tomatoes and spinach, cooked lightly in extra virgin olive oil. In the case of hepatitis C, which is a selenium- and zinc-sequestering virus, special attention should be given to the intake of these minerals and moderate supplementation considered.
(* grape seed extract is a plant polyphenol, contains no fats, and is not to be mistaken for grape seed oil which is high in omega 6 PUFA)

This letter mentions the intriguing possibility that excess accumulation of NADH is a factor in steatohepatitis. This phenomenon is known as reductive stress and may be relieved by choline, betaine and similar molecules through the generation of methane.

In practice, do such diets work? There have already been a few studies of high-fat diets in fatty liver disease. Considering that these have only covered the carbohydrate-to-fat ratio and ignored choline, PUFAs and antioxidants, the results have been thoroughly encouraging (Note, however, that the average patient changing to an “Atkins-type” diet is likely to eat more eggs than they did before, taking care of the choline angle, and probably more greens and fish).

There were no significant associations between either total caloric intake or protein intake and either steatosis, fibrosis, or inflammation. However, higher CHO intake was associated with significantly higher odds of inflammation, while higher fat intake was associated with significantly lower odds of inflammation. In conclusion, present dietary recommendations may worsen NAFLD histopathology.

The effect of a low-carbohydrate diet on the nonalcoholic fatty liver in morbidly obese patients before bariatric surgery

The findings show that 4 weeks of a very low carbohydrate diet reduces liver fat content and liver size, particularly of the left lobe. This approach may render bariatric surgery or any foregut operations less difficult in morbidly obese patients and may be a useful treatment for nonalcoholic fatty liver disease.

The Effect of a Low-Carbohydrate, Ketogenic Diet on Nonalcoholic Fatty Liver Disease: A Pilot Study

Four of 5 posttreatment liver biopsies showed histologic improvements in steatosis (P=.02) inflammatory grade (P=.02), and fibrosis (P=.07). Six months of a low-carbohydrate, ketogenic diet led to significant weight loss and histologic improvement of fatty liver disease.

 

Last but not least, some case studies from everyone’s favourite blogger, Stephan Guyenet at Whole Health Source. Stephan is someone who has taken into account choline and all the other factors I’ve mentioned. 

Fatty Liver Reversal

Another Fatty Liver Reversal

Another Fatty Liver Reversal, part II


Post script: exercise and fatty liver


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070294/
“Neither moderate-intensity exercise nor total exercise per week was associated with NASH or stage of fibrosis. Meeting vigorous recommendations was associated with a decreased adjusted odds of having NASH (odds ratio (OR): 0.65 (0.43-0.98)). Doubling the recommended time spent in vigorous exercise, as is suggested for achieving additional health benefits, was associated with a decreased adjusted odds of advanced fibrosis (OR: 0.53 (0.29-0.97)).”
Exercise significantly elevates PPAR-alpha in rats
http://www.ncbi.nlm.nih.gov/pubmed/21618160
this gives us a range of strategies and combinations for fatty liver; paleo diets, carbohydrate restriction, ketogenic diets, calorie restriction, time-restricted feeding, and high-intensity exercise.


31 comments:

George Henderson said...

Hmmn.

TTA acts as a peroxisome proliferator-activated receptor alpha (PPARα) agonist and increases mitochondrial fatty acid oxidation in vitro.[1] In rodent studies, TTA has been reported to have other activities such as reducing inflammation[2] and preventing high fat diet induced adiposity and insulin resistance.[3]

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

look, that's very interesting, but I think you can do this stuff pretty well with real food.

Nola Chris said...

Just wanted to say hi! I had lost track of you over the last two years some kind of way. But oddly, yesterday, I was doing a search on paleo diet for HCV and there you were! So much stuff to read - hope you don't mind that I posted this on my blog nolahepper.com? Thanks!

Nola Chris New Orleans, LA USA

George Henderson said...

Cheers Chris!
check out Chris's blog peeps:
http://nolahepper.blogspot.co.nz/
he has posted some interesting first-hand stuff about low-dose naltrexone, triple antioxidant therapy and HCV in the past.

P.S. I just learned what NOLA stands for the other day watching Treme.

Nola Chris said...
This comment has been removed by a blog administrator.
Nola Chris said...

Treme Rocks! And New Orleans is rockin too - the Super Bowl in the midst of Mardi Gras!

Laissez Les Bons Temps Rouler!

btw, I know Chris is androgynous but he's a she, lol.

George Henderson said...

Aha, sorry Chris!
Enjoyed catching up with your blog, good results, congrats!

Galina L. said...

I had been having problems with my inflamed gallbladder since 10 years old, it was removed when I was around 40 y.old, so I spent most of my life on a low-fat diet because it was the standard recommendation. Now it is a VLC diet, but still in the back of my mind there is a deeply engraved sensation that a fat must be making liver work harder because it needs more bile for the digestion.

George Henderson said...

If you couldn't digest the fat, it would go right through you. And I don't think the liver knows how much fat is in the gut, it's the gall bladder's job to know that.

If you think that our ancestors sometimes overate very fatty meals as a matter of survival, like primitive peoples today will gorge themselves on fatty meat on the relatively rare occasions when they can get it, it may be that the full gallbladder storage isn't needed for ordinary meals, even VLC ones.

The appendix will grow back after an appendectomy in a quarter of cases and I wonder if in some cases bile ducts might re-form into something like a gall bladder.

George Henderson said...

Also, the gall bladder protects the empty gut from the effects of bile. Removal of the gall bladder can cause
"continuously increased bile flow into the upper GI tract, which may contribute to esophagitis and gastritis. The second consequence is related to the lower GI tract, where diarrhea and colicky lower abdominal pain may result".
http://emedicine.medscape.com/article/192761-overview

So it might actually be good to have fat in the diet to soak up the bile after gall bladder removal.

Galina L. said...

Thank you for your response. My appendix was removed too.I noticed that human body is adoptable when my gallbladder was removed, then gradually I stopped having troubles with food then was able to eat more and more fat without diarrhea. Is it a bad idea to fast with removed gall-bladder?
I always like reading your comments on blogs.

George Henderson said...

is it a bad idea to fast? Probably it would be immediately after the operation. But I imagine you would be able to tell if it was harming your gut in the way that article describes.
Cheers Galina, like me you have an interest in the sociological side of diet and I like reading your observations of what people actually ate. The history of food, water, and disease - not just the paleo history - is where the answers lie, or at least, you can't make sense of things without looking back over the past few hundred years.
That's what I like most about Taubes - his respect for the researchers of the past.

Indy Jill said...

Love the blog George, though a lot of the science goes whoosh, right over my head :-)

I'm dealing with the aftermath of fatty liver and pancreas, namely Type 2 diabetes and though I'm following LCHF and am substantially weight reduced, I'm still at the upper end of normal BMI and typical apple belly despite this, so now thinking about the Newcastle Diet.

Anyhoo, decided to come back to this post and re-read - if you haven't noticed, it seems M. Guyenet has removed those posts from his blog, so you might want to remove the dead links?

Cheers from Oz :-)

George Henderson said...

Thanks - if I get time, I'll rewrite the blog.
Have you tried the Perfect Health Diet? This seems to be good for sustained weight loss. Low-carb is good for beginning, and for clearing immediate health issues, but even Atkins re-introduced some carbs to make his diet sustainable. Some people (insulin resistant) lose more weight with VLC, others (normal insulin sensitivity) actually do better with carbs.
http://www.ncbi.nlm.nih.gov/pubmed/15897479
Newcastle diet is one way of doing it. One guy fasted for over a year.
http://www.abc.net.au/science/articles/2012/07/24/3549931.htm

George Henderson said...

Proper version of the 382 day fast:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2495396/

George Henderson said...

I was able to fix those links.
For future reference change "wholehealthsource" to "wholehealthsources" in the URL to get the new version of most of Stephan's older posts.

Indy Jill said...

Thanks for fixing the links George, I'll get busy with more reading.

I should have said that I'm on a very clean version of primal LCHF - no packaged/processed food at all, no grains, no legumes, minimal dairy but I didn't go onto this diet until after I'd lost most of the extra weight using the conventional "HCLF" lowcal Weight Watchers type of diet. Switched to LCHF after reading Jenny Ruhl's Blood Sugar 101 book then gradually became more primal/paleo.

No longer counting carbs these days, but probably averaging 50-80g per day. I do occasionally eat pumpkin, sweet potato, rice (very rarely). I suppose I could try adding back lentils, though my brief excursion into potato starch/plantain flour was a nightmare of SIBO type symptoms (which terrified me frankly as no way do I want to go back to the kind of dysbiosis I used to suffer with), depression and joint pain. Ugh!

Was doing much better weight and body fat wise when taking 1x 500mg ER Metformin, but had to stop taking it due to bleeding gastritis and low ferritin levels. Have put back on around 4kg since stopping and still have ongoing digestion issues which have improved hugely since stopping grains/metformin, but not 100% sorted yet. My fasting BG is not behaving itself at all, though my post prandial levels are usually good if there aren't too many carbs.

After reading some of Proessor Taylor's papers (incl. http://www.medscape.com/viewarticle/781719) the VLCKD Optifast 8 week Newcastle Diet makes a lot of sense from the Type 2 angle, though I do wonder how my gut would cope with all that processed "pretend" food nowadays. I really wish I could turn back the clock to my diagnosis and have gone straight onto that diet, sigh.

Maybe one day I'll be able to twist my GP's arm into letting me have a repeat of the ultrasound that diagnosed the fatty liver and pancreas before my Type 2 was confirmed as I think the comparison could be useful, but they seem to be tightening the diagnostic tests 'belt' in Oz over the past year or so :-(

Thanks again for the link and excellent blog.

George Henderson said...

Surely you could do Newcastle with real food? liver, for example.
Interesting what you say about metformin, there's a post somewhere here where I discuss a potato-starch like mechanism for metformin.
http://hopefulgeranium.blogspot.co.nz/2013/11/metformins-unusual-mechanisms-lower.html
Ever get checked for H. Pylori? Just a thought.
There are supplements that lower fasting BG; olive leaf extract probably the best (and not that different from olive oil polyphenols, so well tolerated).
How high is fasting BG and HbA1c? Having these elevated a bit may not be an issue if insulin is low.
In other words, if you're "pre-diabetic" but not eating food that will make you diabetic - sugar, refined carbs, and seed oil - it doesn't necessarily mean a thing.
Especially if post-prandial BG is good. Because post-prandial BG can potentially go much higher, and obviously push insulin much higher, than fasting BG.
My non-fasting BG is great on low-carb, but my fasting BG isn't much lower - at the very top of the normal range. This doesn't worry me - it's like having high LDL-C when blood pressure, TG and HDL are all good.

Indy Jill said...

Funny you should mention liver – I tried lamb’s liver for the first time in my life this week and hated it – texture, after taste, even the smell. Not unexpected though as my mother wouldn’t cook offal (her own experiences being forced to eat it as a child during the depression). Plus it went though me like a dose of salts, LOL. Maybe I’ll try again with heart or kidney or cut it up even finer and mask it with other flavours. Oh to have my own chef :-)

I did have the initial problems you describe in that post with metformin, but they settled quickly – I actually thought I was tolerating it well and didn’t realise the ongoing damage that was happening until after an endoscopy made it clear. I’d never actually had acute gastritis till then so had no idea what was causing the pain. It was my third endoscopy in as many years for various types of ongoing upper GI distress (pretty sure now previous issues were SIBO/gluten related as symptoms disappeared completely after 2 lots of antibiotics for something else and stopping grains) but the bleeding/gastritis pain only occurred after taking metformin. I’ve had multiple h. pylori tests and they’ve all been negative.

Thanks for the tip about olive leaf extract – I’ll get some and try it to see if it helps.

I’ll get my latest HbA1c results this week, but the last one was 5.7% (39 mmol/ml; avg. blood glucose of 6.5 mmol/ml). My fasting is always higher in summer for some reason but it didn’t really bother me that it was mostly in the 6’s since low carb mostly keeps post prandials under 7.8 where the damage supposedly starts to accelerate. When I started getting fasting readings up to 7.7, I started to worry. Usually only happens a couple of times a week, but it’s way higher than I want it to be, especially since sometimes that high fasting level will impact my levels for the rest of the day – though at other times eating breakfast seems to reset to my usual lower levels.

According to the Aussie docs, I’m a “mild” Type 2 – whatever that means. At diagnosis my HbA1c was 6.5% and the OGTT to confirm the diagnosis was fasting 6.4 (which it still is most days – LCHF doesn’t seem to have made any difference to it, nor did weight loss of 14 kgs and daily exercise, so seems there’s still some IR going on?), @ 1 hr 14.2, @ 2 hrs 12.9.

I did read of a few people doing Newcastle with real food, 600-800 cals per day, so that might be an option. I only have max. 8 kgs left to lose before I’d pass into underweight BMI, so I might get lucky like that Doughty guy and be done in a week or two.

Thanks for your help, George.

George Henderson said...

Do you take any probiotics? Rueterii may be best for gastritis, and bifidus helps with gut sensitivity. If you get the right one it seems to put extra mucus in the stomach.
Also, have you ever tried spirulina?
Has an anti-HCV and liver protecting action, but that's at a fairly high dose; but something I found went well with probiotics. Aloe vera juice also helped.
This adds up to a lot of stuff, but I imagine some you've tried, others will be harder to get.
I see sprirulina and aloe vera juice as prebiotic foods that help good bacteria, without hugely promoting bacterial growth.
Bifidus, spirulina, aloe are training the gut immune cells both to be more tolerant, and more in control.

Indy Jill said...

Thanks for the advice re spirulina and aloe - haven't tried either yet so I'll keep them in mind.
I've been taking various generic types of probiotics for a while, but admit don't know much about the various strains, so will keep an eye out for the ones you mention.
I eat sauerkraut most days and have been brewing/drinking kombucha for a few months, slowly increasing the amount I drink. It's an acquired taste as I brew it for at least 14 days to minimise residual sugar and impact on BG, so quite acidic, but still enjoyable. The flavour is definitely growing on me.
My gut is a lot more settled than it was back in the metformin days and I only very rarely get gastritis-like twinges these days; also no central or gallbladder pain any more, which is a huge relief as was in serious discussions with GI specialist about gallbladder removal prior to the gastritis diagnosis. Compared to the past few years, things are at least 90+% improved, thank gawd :-)

George Henderson said...

My gallbladder pain cleared up completely, once I cleared the virus. I suspect it was autoimmune in nature, a response to specific bacteria, because it got much worse when I overate fibrous legumes. There are bacteria that can infect the GB, but I found Taurine sometimes relieved it. So I think HCV screwing with cholesterol completion was one factor, and some kind of sensitivity to a bacteria might have been another.

Indy Jill said...

Someone posted this video on a diabetes forum I go to and I thought you might find it interesting - Prof. Taylor presenting the Newcastle Diet results:

http://www.fend-lectures.org/index.php?menu=view&id=94

George Henderson said...

That video's quite fascinating, Dr Taylor knows his stuff.

Indy Jill said...

I'm going down the rabbit hole now, LOL.

Excellent site and Youtube videos posted by Christoph Hollis on Wooo's blog. A Canadian nephrologist called Jason Fung on the hormonal aetiology of obesity/diabetes/insulin resistance - he uses alternate day fasting and variations of fasting on his patients.

I'm now over 36 hours of my first fast and doing well so far - heaps easier than diet shakes and/or counting calories. Just wish now I could get my hands on a CGM to track my BG 24x7.

http://kidneylifescience.ca/general/the-carbohydrate-insulin-hypothesis-is-wrong-hormonal-obesity-vi/

His lectures (over 7 hours of 'em) are well worth watching:
https://www.youtube.com/channel/UCoyL4iGArWn5Hu0V_sAhK2w

The overview video for reversing diabetes is:
https://www.youtube.com/watch?v=mAwgdX5VxGc

Fascinating stuff!

Kino Kuniya said...

Appreciate it for sharing this great article. I agree that this combined stresses involving nutrient depletion and toxicity brings about liver stress, malfunction and ultimately ailment. Get to recognize a supplementary meals call Lifestream Chlorella is actually good to treat this disease. Some review about it topic at:
http://kidbuxblog.com/dealing-with-liver-stress/

Silvia Price said...

"PPAR-alpha is upregulated by intracellular peroxidation of DHA, by carbohydrate restriction, and by fasting, as well as by the flavanone naringenin, an antioxidant found in grapefruit, oranges and tomatoes."

Naringenin also inhibits CYP3A4 which allows the virus to move from cell to cell. HOWEVER, Naringenin is also known to possess a very high one electron redox potential and to have the ability to act as a potent prooxidant, reducing Glutathione levels in experimental systems like phenol and Acetaminophen. Large amounts of grapefruit juice have been reported to actually have the ability to cause the same acute liver failure phenomenon as Tylenol.

George Henderson said...

That's good to know, I'd only recommend eating those foods maybe, not using a high-dose supplement. Grapefruit and orange juice can raise cancer risk because they are photosensitising agents, so promote damage from UV exposure.

"Individuals more susceptible to sunburn as a child or teenager and those who had higher exposure to direct sunlight were at highest risk of melanoma from whole grapefruit consumption, the researchers found.

Orange juice was also associated with greater melanoma risk, which the researchers say is most likely because consumption of this product was much higher than consumption of other citrus products.

Though Dr. Wu and colleagues did not investigate the mechanisms underlying the association between citrus fruit consumption and melanoma risk, they speculate that it may be because the fruits are rich in psoralens and furocoumarins, which are believed to make the skin more sensitive to the sun.

"These substances are potential carcinogens, as found in both mice and humans. Psoralens and furocoumarins interact with UV light to stimulate melanoma cells to proliferate," explains Dr. Marianne Berwick, of the University of New Mexico in Albuquerque, in an editorial linked to the study.

However, the team notes no association was found between consumption of other foods rich in furocoumarins - such as celery and carrots - and increased risk of melanoma. But Dr. Wu says this is likely because people often cook these vegetables, and the heat reduces furocoumarin levels."

http://www.medicalnewstoday.com/articles/296087.php

Miyushi Izumisa said...

Good sharing, yes, liver dysfunction adversely affects the digestive, immune, endocrine, circulatory and nervous systems in a variety of ways. I would recommend Lifestream Chlorella supplement. It contains a high concentration of chlorophyII, Chlorella Growth Factor (CGF), nucleic aids, amino acids, enzymes, antioxidants, vitamins and minerals all beneficial to overall liver health maintenance and restoration. Read more at:
http://kidbuxblog.com/dealing-with-liver-stress/

George Henderson said...

I'll leave this ad here, because Chlorella and Spirulina do improve liver function, and Lifestream is a reliable brand. You can do worse. Nutrition is probably not the mechanism here though.

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