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  #1   ^
Old Sun, Feb-18-18, 11:22
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teaser teaser is online now
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Default How a carb-restricted diet battles fatty liver disease

https://www.sciencedaily.com/releas...80215165152.htm

Quote:
New details about how a carbohydrate-restricted diet improves metabolism were revealed in a study published today, which could lead to improved treatments for non-alcoholic fatty liver disease (NAFLD).

A research team in Sweden examined the effects of reduced carbohydrate consumption -- without an accompanying reduction in calorie intake -- by putting 10 subjects with obesity and high liver fat on a two-week diet. The study, which involved KTH Royal Institute of Technology's SciLifeLab research center, combined clinical and big data analysis to determine the subsequent changes in metabolism and gut bacteria.

By doing so, they identified why the subjects showed "rapid and dramatic" reductions of liver fat and other cardiometabolic risk factors, along with marked decreases in synthesis of hepatic fat. Published today in Cell Metabolism, the work was authored by researchers from KTH, University of Gothenburg and other international collaborators.

Adil Mardinoglu, a systems biology researcher at KTH, says that the subjects were restricted to an isocaloric, low-carbohydrate diet with increased protein content. The researchers found that the metabolism of dangerous hepatic lipids was "strongly linked" to rapid increases in B vitamins and the bacteria that produce folic acid.

This benefit was coupled by a reduction in the expression of genes that are involved in fatty acid synthesis, and an increase in the expression of genes involved in folate-mediated one-carbon metabolism and fatty acid oxidation.

"A carbohydrate-restricted dietary intervention such as the one we used can be an efficient treatment strategy for a severe health problem, as medical science continues the development of new drugs," Mardinoglu says.

The study relied upon a combination of systems medicine and advanced clinical studies, with close interaction between experts in systems medicine, basic scientists, nutritionists and clinicians. Combining forces enabled the team to apply a "multi-omics" approach, which means integrating multiple data sets from the body's omes (genome, proteome, transcriptome, etc.) to identify biomarkers.

"We've moved from an era where scientists could work individually and command -- in one laboratory -- everything they needed, to a world that's much more interactive," Mardinoglu says.

Lead author Jan Boren, a professor at University of Gothenburg, says: "We found that the diet, independently of weight-loss, induced rapid and dramatic reductions of liver fat and other cardiometabolic risk factors, and revealed hitherto unknown underlying molecular mechanisms.

"It's important, however, to clarify that diets are complicated and that one type of diet does not fit everyone. For example, subjects with hypercholesterolemia should be careful." Liver fat is the earliest abnormality in the pathogenesis of both NAFLD and alcoholic fatty liver disease (AFLD) due to metabolic risk factors associated with insulin resistance and metabolic syndrome in the presence or absence of alcohol consumption.

Therefore, the strategies the research team identified could be used also for the treatment of AFLD patients, Boren says.


With diabetes etc. we always here that blood glucose improvements are only due to weight loss, and generally that improvements with low carb are just due to weight loss. This claim doesn't make sense in light of real world observations by people following Bernstein etc., I have no doubt that better blood glucose can be had without weight loss. Weight loss has some effect, but some studies to make it more clear just how much benefit comes from weight loss, how much from carb restriction would be nice.
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  #2   ^
Old Sun, Feb-18-18, 15:43
dcc0455 dcc0455 is offline
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Its not a study, but is my experience. When I was over 200 lbs, my A1C was in the prediabetic range. As my weight went down, eating low carb, my A1C dropped to normal range. At some point, I added back some foods like oatmeal, beans and apples, and my A1C went back up to prediabetic, even though I continued to lose weight. Going back to a stricter low carb put me back in the normal range. Being prediabetic is fairly new to me, so I don't know if is is normal to fluctuate like that, or if it can be correlated to carbs, but so far it seems to be carbs more than weight.
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  #3   ^
Old Mon, Feb-19-18, 14:26
SabreCat50 SabreCat50 is offline
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I posted this originally in the "Cholesterol/Heart" forum:
My wife and I got the same diagnosis today from our doctor. We both have fatty livers and high (total & LDL) cholesterol.

We both had good total/HDL ratios so the doctor was willing to let that slide with regards to heart health. (Whew! I didn't have to argue with her on the issue of statins.)

But she said that high (total & LDL) cholesterol can increase the infiltration of fat into the liver. Since our liver enzymes were normal and we are otherwise healthy, she didn't have any specific recommendations except to eat fewer carbs .

But here's the thing -- we have been on low carb for almost six years!

Does anyone have any insight into this?

I was questioned - rightly so - if we are truly low carb. I would have to say yes. No sugar or grains. Yes on nut flours/sugar alcohols / dark chocolate, but no on high-carb veggies.

In any case, while I am heartened by the research mentioned by the OP, I am at a loss for why my wife and I both came down with fatty livers.
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  #4   ^
Old Mon, Feb-19-18, 16:52
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teaser teaser is online now
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There were some missteps in studying ketogenic diets in mice where the ketogenic diets were choline deficient, leading to fatty liver. So, do you like eggs, liver?

Free fatty acids provide material for triglyceride storage in the liver, so it's not that weird if a diet or approach, low carb, fasting, that increases free fatty acids leads to an elevation of liver fat, I guess the question is, what usually prevents this? Something that can happen with type II diabetics when they go on insulin initially, their liver fat reduces. This is thought to be due to more effective fat trapping in subcutaneous fat, the liver is exposed to lower free fatty acid levels, especially after a meal when it's busy dealing with excess carbohydrate. People talk a lot about de novo synthesis of fatty acids from carbohydrate, but by far the most efficient way to fatten the liver is with preformed free fatty acids so that all that's really needed is re-esterification/triglyceride synthesis.
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  #5   ^
Old Mon, Feb-19-18, 21:00
SabreCat50 SabreCat50 is offline
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Quote:
Originally Posted by teaser
There were some missteps in studying ketogenic diets in mice where the ketogenic diets were choline deficient, leading to fatty liver. So, do you like eggs, liver?

Free fatty acids provide material for triglyceride storage in the liver, so it's not that weird if a diet or approach, low carb, fasting, that increases free fatty acids leads to an elevation of liver fat, I guess the question is, what usually prevents this? Something that can happen with type II diabetics when they go on insulin initially, their liver fat reduces. This is thought to be due to more effective fat trapping in subcutaneous fat, the liver is exposed to lower free fatty acid levels, especially after a meal when it's busy dealing with excess carbohydrate. People talk a lot about de novo synthesis of fatty acids from carbohydrate, but by far the most efficient way to fatten the liver is with preformed free fatty acids so that all that's really needed is re-esterification/triglyceride synthesis.

Hmm. I'm not sure what the upshot of this is. We eat plenty of eggs and some liver. So are we getting enough choline? And this is important why?

But you also say that (an excess of?) free fatty acids will fatten the liver. Does this mean eating too much fat is bad?

Thanks for your help.
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  #6   ^
Old Tue, Feb-20-18, 08:05
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teaser teaser is online now
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The short answer for choline being important is that in human and animal experiments of choline deficiency, the liver gets fatty.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729018/

Quote:
Humans must eat diets containing choline [1] because its metabolite phosphatidylcholine constitutes 40–50% of cellular membranes and 70–95% of phospholipids in lipoproteins, bile and surfactants [2]; it is needed to form acetylcholine, an important neurotransmitter [2]; its metabolite betaine is needed for normal kidney glomerular function, and perhaps for mitochondrial function [2]; and it provides one-carbon units, via oxidation to betaine, to the methionine cycle for methylation reactions


Since lipoprotein particles are how the liver exports fat, that 70-95 percent of phospholipids from choline seems important.

Quote:
Choline’s role in maintaining liver function: new evidence for epigenetic mechanisms


Dietary fat being bad--I wouldn't say that outside of certain contexts. Like, I eat lots of butter, but wouldn't want to assume that if I started eating lots of chocolate croissants that the butter in them would be doing me any good. When it comes down to it, we all carry more than enough subcutaneous fat to be walking around with elevated free fatty acids without ever eating fat, that's more of a question of appropriate fat trapping by subcutaneous fat cells.

A popular fatty liver model in rodents is methionine-choline deficiency combined. Methionine restriction seems to compromise fat trapping, not necessarily a bad thing, in the rodent models of longevity where methionine restriction increases lifespan, this is accompanied by a greater dependence on fat for energy during fasting--so the same thing that contributes to fatty liver in one study might increase lifespan in another. In the choline and methionine restricted animals, it's thought that the methionine restriction increases the load of fat that the liver must cope with, which would be fine except that the choline restriction makes it difficult for the liver to cope. In effect the methionine restriction increases the choline requirement.
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  #7   ^
Old Tue, Feb-20-18, 10:24
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Meme#1 Meme#1 is offline
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Choline is very interesting and in fact I purchased some just last month. I bought the combination of Choline/Inositol. I remember it doing me a lot of good a few years ago when I had more stress from outside sources than any one person should ever have to deal with.

Teaser, when you said this,
Quote:
Dietary fat being bad--I wouldn't say that outside of certain contexts. Like, I eat lots of butter, but wouldn't want to assume that if I started eating lots of chocolate croissants that the butter in them would be doing me any good


it reminded me of when DH had Broccoli/rice casserole at the cafeteria and I tried to tell him it didn't matter if it had Broccoli because it's full of rice
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  #8   ^
Old Wed, Feb-21-18, 13:37
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JEY100 JEY100 is offline
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Glenn, did you see my last post on your other thread? http://forum.lowcarber.org/showpost...961&postcount=4
(trying to think of reasons other than diet...age (like we can do anything about that), thyroid (but unlikely both of you), etc.
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  #9   ^
Old Wed, Feb-21-18, 15:20
M Levac M Levac is offline
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Quote:
Originally Posted by SabreCat50
I posted this originally in the "Cholesterol/Heart" forum:
My wife and I got the same diagnosis today from our doctor. We both have fatty livers and high (total & LDL) cholesterol.

We both had good total/HDL ratios so the doctor was willing to let that slide with regards to heart health. (Whew! I didn't have to argue with her on the issue of statins.)

But she said that high (total & LDL) cholesterol can increase the infiltration of fat into the liver. Since our liver enzymes were normal and we are otherwise healthy, she didn't have any specific recommendations except to eat fewer carbs .

But here's the thing -- we have been on low carb for almost six years!

Does anyone have any insight into this?

I was questioned - rightly so - if we are truly low carb. I would have to say yes. No sugar or grains. Yes on nut flours/sugar alcohols / dark chocolate, but no on high-carb veggies.

In any case, while I am heartened by the research mentioned by the OP, I am at a loss for why my wife and I both came down with fatty livers.

Personally, I believe dietary fat fixes fatty liver. In a mouse experiment, it was found that dietary fat activates the PPAR-alpha pathway, which in turn clears fat deposits from the liver: https://www.ncbi.nlm.nih.gov/pubmed/16054078 I can't say if it's also true in humans, but I choose to believe that anyway. As far as I'm aware, there's only two things that cause fatty liver - alcohol and fructose. I mean, maybe there's other things, but dietary fat ain't one of them.

The thing about "cholesterol increasing infiltration of fat into the liver", first time I hear something like that. Ima say it's total complete BS. A quick search reveals it's about NAFLD, which is caused by fructose, not dietary fat or cholesterol or anything else. The language used is "factors" and such, which means there's no experimental data. So, basically, somebody (some pharma rep most likely) told the doc something, the doc drew a conclusion in his mind, then he told you that conclusion but without a iota of evidence to support any of it, except of course his doctorate and status that comes with it. I love docs, they spew crap out their mouths and we take it seriously.

About the question whether you actually eat low-carb. It's quite simple. Either you follow as best you can some popular diet book like Atkins or Protein Power for example, or you follow your own plan which you devised from experience and/or from one of those low-carb diet books. For example, Atkins advises to eat less than 20g/day for induction, then go up the carb ladder to find out what your carb threshold is, get back down a bit to lose fat at a constant pace, then keep it there once you reach goal for on-going maintenance. I don't know what your carb threshold is, but you should know it if that's what you're doing. Anyways, if it's 50g/day for example, then the doc tells you to eat less than that (but he doesn't know how much carbs you eat in the first place), I'm pretty sure it's already low enough. Ima say ignore the doc on that one. After 6 years doing LC, you probably know a whole lot more than he does about diet and especially low-carb.

I'm wondering how the doc diagnosed fatty liver? If all is normal, how did he find that the liver was not normal? For high cholesterol, I would personally ignore that diagnosis, but if I'm not mistaken high cholesterol used to be a marker for low thyroid function so if you're worried about that it's a simple test and an equally simple fix - just eat more iodine. On the other hand low-carb will cause cholesterol to rise somewhat. It's important to keep in mind that when we talk about cholesterol, we don't talk about cholesterol, instead we talk about lipoproteins. It's also important to know which type of test the doc used to measure it. There's the actual, then there's the estimated/calculated. If it's the estimated/calculated, ignore it, low-carb makes that test lie. Finally, when it comes to lipoproteins, what matters most is particle size, not particle quantity. The bigger the lipoproteins, the better. Low-carb just happens to make these bigger, which is one reason it makes the estimated/calculated test lie. The thing about particle size is that smaller lipoproteins are more easily oxidized and that's a bad thing, or at least that's how I understand it.

Anyways, if the article is correct about low-carb, B vitamins and folic acid to fix fatty liver, I wouldn't worry about a thing if you're been doing LC for the past 6 years. Which means either the doc misdiagnosed fatty liver, or there's something else going on and you should figure out what it is and then fix that.
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  #10   ^
Old Wed, Feb-21-18, 16:00
SabreCat50 SabreCat50 is offline
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Quote:
Originally Posted by JEY100
Glenn, did you see my last post on your other thread? http://forum.lowcarber.org/showpost...961&postcount=4
(trying to think of reasons other than diet...age (like we can do anything about that), thyroid (but unlikely both of you), etc.

Janet: Yes I did, thanks.

My trig/ hdl is 79/72 ~ 1.1. My wife's is 118/92~1.3 So no problems there. Our thyroid numbers were good as were the liver function tests. Our only "symptom" was the presence of fat on the ultra sound!

I did have Hep C but have been free for over 10 years. And my wife has had no such problems.

Go figure.
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  #11   ^
Old Wed, Feb-21-18, 16:12
SabreCat50 SabreCat50 is offline
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Quote:
Originally Posted by teaser
The short answer for choline being important is that in human and animal experiments of choline deficiency, the liver gets fatty.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729018/



Since lipoprotein particles are how the liver exports fat, that 70-95 percent of phospholipids from choline seems important.



Dietary fat being bad--I wouldn't say that outside of certain contexts. Like, I eat lots of butter, but wouldn't want to assume that if I started eating lots of chocolate croissants that the butter in them would be doing me any good. When it comes down to it, we all carry more than enough subcutaneous fat to be walking around with elevated free fatty acids without ever eating fat, that's more of a question of appropriate fat trapping by subcutaneous fat cells.

A popular fatty liver model in rodents is methionine-choline deficiency combined. Methionine restriction seems to compromise fat trapping, not necessarily a bad thing, in the rodent models of longevity where methionine restriction increases lifespan, this is accompanied by a greater dependence on fat for energy during fasting--so the same thing that contributes to fatty liver in one study might increase lifespan in another. In the choline and methionine restricted animals, it's thought that the methionine restriction increases the load of fat that the liver must cope with, which would be fine except that the choline restriction makes it difficult for the liver to cope. In effect the methionine restriction increases the choline requirement.


Teaser: I looked up somethings on choline and it does say that not everyone can utilize all of the choline in the diet. It could be DNA or liver damage. Or age??

So I am tempted to supplement with choline. It's not so easy for the wife- she's very sensitive to any supplement.

Unfortunately, there isn't a simple blood test that I could find for measuring choline levels. I could just eat more eggs
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  #12   ^
Old Wed, Feb-21-18, 18:59
SabreCat50 SabreCat50 is offline
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Quote:
Originally Posted by M Levac
...

I'm wondering how the doc diagnosed fatty liver? If all is normal, how did he find that the liver was not normal? For high cholesterol, I would personally ignore that diagnosis, but if I'm not mistaken high cholesterol used to be a marker for low thyroid function so if you're worried about that it's a simple test and an equally simple fix - just eat more iodine. On the other hand low-carb will cause cholesterol to rise somewhat. It's important to keep in mind that when we talk about cholesterol, we don't talk about cholesterol, instead we talk about lipoproteins. It's also important to know which type of test the doc used to measure it. There's the actual, then there's the estimated/calculated. If it's the estimated/calculated, ignore it, low-carb makes that test lie. Finally, when it comes to lipoproteins, what matters most is particle size, not particle quantity. The bigger the lipoproteins, the better. Low-carb just happens to make these bigger, which is one reason it makes the estimated/calculated test lie. The thing about particle size is that smaller lipoproteins are more easily oxidized and that's a bad thing, or at least that's how I understand it.

Anyways, if the article is correct about low-carb, B vitamins and folic acid to fix fatty liver, I wouldn't worry about a thing if you're been doing LC for the past 6 years. Which means either the doc misdiagnosed fatty liver, or there's something else going on and you should figure out what it is and then fix that.

It was the radiologist who identified the fatty liver from the ultrasound.

I found a website with images called (I kid you not!) www.fatty-liver.com . While the website has some good information, the "cure" requires eating less fat!
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  #13   ^
Old Wed, Feb-21-18, 23:58
M Levac M Levac is offline
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OK, I can think of vitamin A. Do you guys supplement with it? If yes, stop. Either way you can read my journal for my personal experience with a ultra high dose 15 day protocol I used to figure out what's wrong with me. To summarize, vitamin A is one of a handful of things I tried that had any effect, and this effect was also one of the strongest and most beneficial for me.

The thing about vitamin A and the liver is that it accumulates at some point, especially with regular daily supplements for years. I didn't do that, I did a 15 day therapeutic protocol, then I stopped. A few months later, I did a single day high dose protocol to test for any effect - no effect. From this, I conclude I had a physiological vitamin A deficiency, and I fixed it with that protocol, i.e. I filled up the tank so to speak, and this tank happens to be the liver. The cause of this deficiency is, I also concluded, a chronic infection I've had for several years now, and I still don't know exactly what it is.

Also, vitamin A is fat-soluble, which means fat is required for its metabolism, and vitamin A is stored in the liver, which means dietary fat is likely to fix vitamin A toxicity in the liver. It's a sort of paradox here because vitamin A is stored in the liver (up to two years' worth of it, in fact, about 6 million IU's), so the liver should be able to handle it no problem, except when there's little dietary fat coming in, then vitamin A becomes toxic.

Finally, when we're talking about fat or anything related to fat like fatty liver for example, I believe insulin is always involved in some way. It makes sense when researchers find that cutting carbs has an effect on fatty liver, when the first thing that happens when we cut carbs is that insulin drops, or at least any spike from a meal is much lower than it used to be. Never mind that the researchers don't talk about insulin in this particular study, I believe they should.

Bear in mind that's just how I see it, not necessarily how it actually works, so you read up on it if you're worried about any of it.
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  #14   ^
Old Thu, Feb-22-18, 15:46
SabreCat50 SabreCat50 is offline
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Quote:
Originally Posted by M Levac
OK, I can think of vitamin A. Do you guys supplement with it? If yes, stop. Either way you can read my journal for my personal experience with a ultra high dose 15 day protocol I used to figure out what's wrong with me. To summarize, vitamin A is one of a handful of things I tried that had any effect, and this effect was also one of the strongest and most beneficial for me.

The thing about vitamin A and the liver is that it accumulates at some point, especially with regular daily supplements for years. I didn't do that, I did a 15 day therapeutic protocol, then I stopped. A few months later, I did a single day high dose protocol to test for any effect - no effect. From this, I conclude I had a physiological vitamin A deficiency, and I fixed it with that protocol, i.e. I filled up the tank so to speak, and this tank happens to be the liver. The cause of this deficiency is, I also concluded, a chronic infection I've had for several years now, and I still don't know exactly what it is.

Also, vitamin A is fat-soluble, which means fat is required for its metabolism, and vitamin A is stored in the liver, which means dietary fat is likely to fix vitamin A toxicity in the liver. It's a sort of paradox here because vitamin A is stored in the liver (up to two years' worth of it, in fact, about 6 million IU's), so the liver should be able to handle it no problem, except when there's little dietary fat coming in, then vitamin A becomes toxic.

Finally, when we're talking about fat or anything related to fat like fatty liver for example, I believe insulin is always involved in some way. It makes sense when researchers find that cutting carbs has an effect on fatty liver, when the first thing that happens when we cut carbs is that insulin drops, or at least any spike from a meal is much lower than it used to be. Never mind that the researchers don't talk about insulin in this particular study, I believe they should.

Bear in mind that's just how I see it, not necessarily how it actually works, so you read up on it if you're worried about any of it.


Our vitamin A supplementation is via a generic senior multivitamin -- 2500 IU (40% RDA) per day. Nor do we eat carrots!

I wish we had an easy way to measure insulin. It would certainly answer a lot of questions.

Thanks.
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  #15   ^
Old Thu, Feb-22-18, 18:49
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Dodger Dodger is offline
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