Saturday, March 20, 2010

Fatty Liver: It's not Just for Grown-ups Anymore

The epidemic of non-alcoholic fatty liver disease (NAFLD) is one of my favorite topics on this blog, due to the liver's role as the body's metabolic "grand central station", as Dr. Philip Wood puts it. The liver plays a critical part in the regulation of sugar, insulin, and lipid levels in the blood. Many of the routine blood tests administered in the doctor's office (blood glucose, cholesterol, etc.) partially reflect liver function.

NAFLD is an excessive accumulation of fat in the liver that impairs its function and can lead to severe liver inflammation (NASH), and in a small percentage of people, liver cancer. An estimated 20-30% of people in industrial nations suffer from NAFLD, a shockingly high prevalence (1).

I previously posted on dietary factors I believe are involved in NAFLD. In rodents, feeding a large amount of sugar or industrial seed oils (corn oil, etc.) promotes NAFLD, whereas fats such as butter and coconut oil do not (2). In human infants, enteric feeding with industrial seed oils causes severe liver damage, whereas the same amount of fat from fish oil doesn't, and can even reverse the damage done by seed oils (3). [2013 update: obesity is probably the main contributor to NAFLD.  Obesity is associated with ectopic fat deposition in a number of organs, including the liver]

So basically, I think excessive sugar and industrial oils could be involved NAFLD, and if you look at diet trends in the US over the last 40 years, they're consistent with the idea.

I recently came across a study that examined the diet of Canadian children with NAFLD (6). The children had a high sugar intake, a typical (i.e., high) omega-6 intake, and a low omega-3 intake. The authors claimed that the children also had a high saturated fat intake, but at 10.5% of calories, they were almost eating to the American Heart Association's "Step I" diet recommendations**! Total fat intake was also low.

High sugar consumption was associated with a larger waist circumference, insulin resistance, lower adiponectin and elevated markers of inflammation. High omega-6 intake was associated with markers of inflammation. Low omega-3 intake was associated with insulin resistance and elevated liver enzymes. Saturated fat intake presumably had no relation to any of these markers, since they didn't mention it in the text.

These children with NAFLD, who were all insulin resistant and mostly obese, had diets high in omega-6, high in sugar, and low in omega-3. This is consistent with the idea that these three factors, which have all been moving in the wrong direction in the last 40 years, contribute to NAFLD.

* Fatty liver was assessed by liver enzymes, admittedly not a perfect test. However, elevated liver enzymes do correlate fairly well with NAFLD.

** Steps I and II were replaced by new diet advice in 2000. The AHA now recommends keeping saturated fat below 7% of calories.  However, the new recommendations focus mostly on eating real food rather than avoiding saturated fat and cholesterol.


Mavis said...


Patrick said...

"I do have to give the AHA credit however, because their new recommendations focus mostly on eating real food rather than avoiding saturated fat and cholesterol."

It seems lately that what we call the "mainstreams" are slowly starting to see the light. In about 10 years the lipid hypothesis should be on its way out.


Jenny said...

Unfortunately, studies do not support the idea that lowering liver enzymes means you've lowered the amount of liver fat, if you use liver biopsy as the gold standard.

Same thing with metformin. It lowers the enzymes, but biopsy shows very little change.

Even after 6 months on a supervised VLCD biopsy shows very small reductions in liver fat.

Some authors are telling people that a few weeks of LC can reverse liver fat, but this is based on one very questionable study which is an imaging study, not confirmed by biopsy.

I've blogged about this HERE with links.

Todd S. said...

I recall in the movie "Super Size Me" that one of the worst things happening to him (as shown by his blood work) was NAFLD. Of course the doctor blamed it on his "high fat" diet.

At the end of the movie he shows that over 30 days he consumed a full 30lbs of sugar compared to 12lbs of fat (and he gained 25lbs of body weight). And that doesn't even account for the rest of the highly refined carbs like the buns.

Mavis said...


Also, a lot of that fat was trans-fat and omega-6 fats in the fries.

John said...

Several studies show the body fat advantages with coconut oil over tallow, butter, or olive oil. Is there an advantage with coconut fat over beef or butter fat for liver health? Interestingly, I read a paper ( I can't find it) where fat deposits throughout the body were reduced with coconut oil, except in the liver...

L said...

skinless chicken breast is a good idea if ones goal is to keep omega-6 < 4%.

skinless breast (or any lean cut of meat) can be made palatable with butter and/or sweet and spicy sauce. omit sweet component if minimizing fructose.

Innovator said...

Someone is getting close to "book ready" on an idea you've mentioned in one of your comments: "There is a connection between overweight and the diseases of civilization, but it's complex and I'm still trying to understand it." [Feb. 2, 10:04 PM]

Do you have any thoughts yet about weight gain/loss and Fatty Liver Syndrome in the context of the Hyperlipid mantra: "The function of insulin is the inhibition of lipolysis"? I have come to enjoy Peter's work at Hyperlipid very much.

May I suggest that you consider Peter's work as a way to help all of us "Whole Healther's" understand the connection between overweight and the diseases of civilization?

Thanks for all the citations!

Ned Kock said...

Since you mentioned adiponectin Stephan, here is a bit more about this unique hormone secreted exclusively by body fat:

Jonathan Byron said...

>> Do you have any thoughts yet about weight gain/loss and Fatty Liver Syndrome in the context of the Hyperlipid mantra: "The function of insulin is the inhibition of lipolysis"? I have come to enjoy Peter's work at Hyperlipid very much.

Fructose is especially good at inducing fatty liver - even though that sugar doesn't have much a big effect on insulin. Fructose is preferentially metabolized in a few organs, one is the liver. When too much fructose is consumed, the liver will turn it to fat, and the liver accumulates fat.

Anonymous said...

Very timely. I have a NAFLD post brewing as we speak. Steatohepatosis, elevated liver enzymes and NASH are all sort of independent components of the NAFLD spectrum. Unfortunately, you can have steatohepatosis or even NASH with fibrosis (very advanced) in the context of normal ALT levels.

You also do not have to be obese, and there is a fair amount of stetohepatosis even among the "healthy" japanese.

MR spectroscopy is the gold standard for assessing steatohepatosis - I have a paper on that I'll be blogging on.

I put LA first and fructose second, but this is just an educated guess.

My youngest case of steotohepatosis and gallstones so far is an 11 year old boy.

Anonymous said...


I read your NAFLD post. In it, you said:

"So once you have created a new population of fat cells in your liver, while it is possible dietary interventions may reduce the fat they contain, you are not going to get rid of the cells.:

One problem with your reasoning on the reversibility of Steatohepatosis is that there are no new fat cells created in the liver.

The lipid actually accumulates in the hepatocytes, which are liver cells and are not adipocytes.

Also, imaging with MRS is actually superior to biopsy for SH, as the sample size is 10 times larger, so less sampling error. The distribution of changes can be inhomogeneous and can be missed by biopsy.

Bob Bejaan said...

off-topic but might be of interest to people eating lots of kelp/seaweed:

Seaweed to Tackle Rising Tide of Obesity

whats this gonna do to your absorbtion of all those good paleo-friendly fats (and vitamins)?

though if they're talking about adding it to bread and biscuits maybe it'll reduce the omega-6 nonce-sense u absorb (though probably not applicable to paleo folks)

Stephan Guyenet said...

Hi John,

I don't know anything specific about coconut oil related to the liver, except that high-fat feeding with coconut oil doesn't cause fatty liver in rats (despite the fact that they eat WAY more food than chow-fed animals).

Hi Kurt,

I'll look forward to your post.

Hi Bobbejaan22,

Great, we've invented another way to block the absorption of fat, and fat-soluble vitamins along with it. I'm sure going #2 will be super fun when you're taking that stuff. It will be like Olestra but 5 times worse because it's blocking much more fat.

Stanley said...


Contradicting your advice, the BBC reports today that a new Harvard Medical School study suggests we should all eat more vegetable oil.

The BBC report neglected to cite the study. I looked, but couldn't find.

Sounds like epidemiology masquerading as controlled experimentation, but it sounds so ridiculous that it would be worth knowing more. I think many of us readers would appreciate your insights.

I suspect that vegetable oil eaters may suffer fewer heart problems because they also happen to eat more vegetables, as in Asian stir fry, which retard PUFA oxidation. Or perhaps more importantly, they are methionine restricted, which new research suggests may be the dominant reason for the positive effects of caloric restriction. (Asians eat truly disturbing amounts of heat-damaged omega 6 seed oils, but they seem to have low rates of obesity and heart disease.)


donny said...

I seem to be asking variations on this question a lot lately; does the liver do physiological insulin resistance? They've done experiments with diabetic mice; choline deficiency decreases insulin resistance. Choline deficiency can itself cause fatty liver. If the lack of choline keeps the liver fat inactive, discouraging lipolysis, wouldn't this "ameliorate" insulin resistance in the liver?

As a low-carber, I've usually assumed that low carb meant a decreased need for most vitamins, including the b's. But starting out with a fatty liver and visceral fat, this might just not be true.

Normal liver enzymes might be a sign that the liver is not actively storing triglycerides, rather than that it is being cleared of fat. Still a darn sight better than elevated enzyme levels though, no?

JBG said...

Here is the article Stanley mentions:

And here is an editorial about it:

Unfortunately, I don't have time at the moment to read them.

Stephan Guyenet said...

I spoke too soon. The paper in question is a meta-analysis of randomized clinical trials. I'll comment on it once I read it.

Stephan Guyenet said...

OK, this review is total BS. They included the Finnish trial in their analysis, really unbelievable!!

The title of their study says "Meta-Analysis of Randomized Controlled Trials". The Finnish trial was neither randomized, nor blinded, nor controlled!

I'm looking through the data, there are so many problems with this review it's ridiculous. That's probably why it went to PLoS and not NEJM. I may have to post on it.

Justin said...


What is your opinion on the posiblity of higher intakes of supplemental fish oil (4 to 5 grams) causing/facilitating elevated AST/ALT values especially in the context of higher "natural" saturated fat consuption. I have recently experienced this phenomenon. Though, just before having my labs performed I had discontinued the consuption of alcohol about 3 weeks earlier. I used to be a 2 beer a night individual and usually drank on an empty stomach while preparing dinner. I do not have any noticible viceral fat but cholesterol numbers have significantly increased over the past year. NMR shows mostly (90%) large boyant LDL and HDL was between 70 and upper 80's the last two times I had it checked. Trigs ar also low around 40 to 50. I have systimatically elementated the fish oil to see if the enzymes drop back to normal levels. Also, I have heard some anacdotal evedence on the internet of fish oil elevating enzymes and Peter's post on Krause's comentary paper on VLDL degredation and fish oil here:
got me thinking. Any theories would be welcome. Thanks for the awesome blog. BTW, are you originally from Virginia?


Robert Andrew Brown said...


Thanks for the link.

As far as I am aware British Asians have much higher rates of heart disease.

I have not had time to read the paper but am very depressed at the effect this pronouncement will have.

Once you begin to grasp the underlying biology, it makes no sense that high levels of Omega 6 reduce cardiac disease.

The fact the paper relies on the Finnish trials is not a promising start as Stephan points out.

Courtney said...

Stephan said...I'm looking through the data, there are so many problems with this review it's ridiculous. That's probably why it went to PLoS and not NEJM. I may have to post on it.

This study is getting picked up and reproduced f-all *everywhere.* It was even thrown in my face (figuratively) this morning by a vegetarian colleague, who doesn't believe my health improvements have been related to diet change (except in the tired "well, it works for *you* sense). So I am eagerly looking forward to your post.

kilton said...

Stephan -- A post about this study would be much appreciated, as I think it's a bit much for most of us to be able to pick apart effectively.

Dr. B G said...


Didn't know it was in the hepatocytes!

I believe gluten is involved with NASH/NAFLD/'fatty liver' as it is with all calcified, fatty organs (coronary arteries, gallbladder, ovaries/PCOS, pituitary, etc).

I've seen NASH reversal in 1-2mos. People go low carb, semi-gluten free or gluten and cut out fruit.

MCT oil, coconut oil and ghee/butter help also to hasten the reduction in visceral fat, incl those hepatocytes. There are good MCT studies in the Japanese -- they are all 'metabo' though lean phenotyptes, e.g. insulin resistant from ALL THE $*%$&# HIGH CARB RICE.


Dr. B G said...


Great post!

You have 2 prior examples Steve, Sam, respectively, who demo that lower carb and minimal grains/corn/beans help:

Omega-3 and PPAR agonists have bene shown to reverse NASH as well... wonder why!



Ed said...

The abstract of the linked study includes this line:

"Their diets are high in fructose and low in polyunsaturated fatty acid. Their activity patterns are sedentary. These lifestyle features may contribute to liver damage and can be a focus for therapeutic intervention."

They are implying that low PUFA is bad, and perhaps raising it might solve the problem.

This makes me sad, because Stephan reads the study, he finds:

"High omega-6 intake was associated with markers of inflammation. Low omega-3 intake was associated with insulin resistance and elevated liver enzymes."

The abstract, which most people will read and report on, suggests more nut & seed oils, but clearly there is an important nuance that is missing from the abstract. Arg! Political correctness still carries the day, even in research that seems to produce good data.

Stephan, did they note the prevalence of NAFLD in the population in which those children live? I wonder if current childhood NAFLD is higher than the 20%-30% of total population.

Juhana Harju said...


Even if the Finnish trial were excluded, the risk ratio would support the replacement of saturated fats with PUFAs.

Willow said...

Salt too is no friend to the liver, especially a child's liver, and salt is a major contributor to child obesity.

Prescription drugs also damage the liver, yet many parents do not hesitate to give their children painkilling medicine for even very mild pain.

Unknown said...

I am very interested in what I have been reading and am searching for help. I had cholestasis during a surrogate pregnancy 2 yrs ago. Since I have still suffered bouts of itching and especially when on meds. My liver enzymes are always normal however; on a recent catscan a finding of fatty liver was found. I still have itching on and off and was prescribed cholestyramine powder to which I am suffering some body aches, frequent urination etc. I have two little kids and seriously want to live!! I would love your help and knowledge as to what to do for my liver problem I am willing to do whatever it takes. I am suffering from extreme anxiety from this,

Carol B. said...

Hello Stephen, I have gall stones, ultrasonography we see
vesicle filled. I read about a diet with bitter salt and olive oil with lemon. It
cleaning, breakfast and lunch at 2pm without fat. at 18pm
drink the mixture of sour salt (to open the ducts) with lemon and olive oil.
After 2 hours another drink and another 22hs. Drink up and then throw up
the next day to take a more bitter cup of salt and 2 h after the last. The
stones get out in the bathroom, green, dark green old, black ... In
your opinion, how does the path of stones? It is said that it is necessary
to 4 times, 2 in 2 months. Also that because of the olive stone
not "grab or migrates" nowhere because of the salt and bitter no
pain. Do you agree?

stephers said...

Stephan I would be really curious for your opinion on this study:

December 6, 2011 - Nonalcoholic fatty liver disease is not associated with increased all-cause or cardiovascular mortality, according to a study published online November 18 in the British Medical Journal. (Medscape)

I have an interest in livers because I have had elevated liver enzymes for 20+ years, yet ultrasounds, all manner of blood tests, etc. have never been able to explain why.