September 18, 2009

High Fructose Intake Raises Liver Fat

As I blogged last week, it is liver fat not, as we have been told for years, visceral fat, that appears to be responsible for the metabolic disorders associated with obesity.

Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Elisa Fabbrini et al. PNAS Published online before print August 24, 2009, doi: 10.1073/pnas.0904944106>The abstract of the above study is pretty tough going. Fortunately, you can read a clearer explanation of what this study found in this report in Diabetes in Control

Diabetes in Control:Liver Fat Has Greater Impact on Health than Abdominal Fat

A new study reported last week gives important information about an important factor that causes fats to be deposited in the liver: Fructose.

Fructose overconsumption causes dyslipedemia LĂȘ KA, et al. Am J Clin Nutr. 2009 Jun;89(6):1760-5. Epub 2009 Apr 29.

In this study twenty-four human males, 8 normal who were the controls and 16 "healthy offspring of patients with type 2 diabetes" were fed two different diets, each for a week. The first was a control diet (the makeup not specified in the study abstract but undoubtedly it was the the usual high carbohydrate diet favored by nutritionists). Then all the subjects they were fed a diet that contained 3.5 g of fructose per kilogram of the subject's fat free mass and 35% more calories than the control diet.

This is a lot of fructose. Back of the envelope calculations suggest it would be 145 grams of fructose for a 140 lb woman at the high end of normal BMI and 255 grams for a 200 lb man with 20% body fat.

Liver and muscle tissue were studied with 1-H magnetic resonance spectroscopy and insulin resistance was also measured with a two step insulin clamp.

The finding here was that the high fructose/high calorie diet raised intrahepatic cellular lipids--i.e. fats in the liver cells--by 76% in normal people and 79% in those with relatives with Type 2 diabetes.

The high fructose/high calorie diet raised intramuscular cellular lipids much more in controls than people with diabetic relatives--47% in the normals, 24% in those with diabetic relatives. This probably reflects the insulin resistance of the people with diabetic heritages. The high fructose/high calorie diet raised VLDL-triacylglycerols, the lipid fraction most closely linked with heart disease, +51% in controls and 110% in the people with diabetic relatives.

The high fructose/high calorie diet raised fasting hepatic glucose output 4% in control: +4% and 5% in those with diabetic relatives. The researchers also concluded that it decreased the subjects' liver insulin sensitivity.

With this in mind, you'd want to ask yourself what kind of diet would provide 3.5 grams of fructose per pound of body weight each day. Research using data from the 1970s found that
For most sex/age groups nonalcoholic beverages (eg, soft drinks and fruit-flavored drinks) and grain products (eg, sweet bakery products) were the major sources of fructose.
There is only a tiny amount of fructose in wheat, so the fructose attributed to in baked goods here came from the sugar and corn syrup they contained. Table sugar, sucrose, is made of glucose bonded to fructose, and is one half fructose. High fructose corn syrup may be anywhere from 55% fructose to 90% fructose. There is no way of knowing the actual percentage of fructose in any food you buy that lists high fructose corn syrup on the label.

The 1970s data showed that the average person's intake of fructose from all sources averaged 37 grams a day, with young males eating an average of 54 grams a day. Since the 1970s, our food supply has been invaded by high fructose corn syrup which you will find in everything from bread to soup to beans to salad dressing. With 41 grams of high fructose corn syrup in every 12 ounce can of Pepsi, it's likely that the average daily intake is at least double that common in the 1970s. And then there are all those milkshakes-sold-as-coffee-and-tea like the Starbucks Apple Chai Infusion with its 74 g of sugars. . . .

So while the average person might not be eating as much fructose as the amount used in the study that showed high fructose intake causing liver fat build up, they may be eating up to 2/3rds that amount. Given the massive impact the high fructose diet had on liver fat, this latest study adds convincing evidence that fructose does, in fact, play a big part in the so-called "obesity epidemic" and in the rising incidence of Type 2 diabetes.

Another study also reported last week linked second hand smoke to liver fat. This is a mouse study, so it has to be taken with a grain of salt. Still, we know that people who smoke have much higher rates of heart disease than those who don't, so it is worth considering

Science Daily: Second-hand smoking results in liver disease study finds

The exact mechanism occurring in the mouse study is reported thus:
They found that second-hand smoke exposure inhibits AMPK activity, which, in turn, causes an increase in activity of SREBP. When SREBP is more active, more fatty acids get synthesized. The result is NAFLD [non-alcoholic fatty liver disease] induced by second-hand smoke.
As you can see when you visit the web page where I discuss what research knows about the real causes of Type 2 diabetes, there is no one cause. Type 2 Diabetes appears to require the presence of an underlying a genetic flaw but it gets triggered by a long list of environmental factors ranging from pesticides, to pharmaceutical drugs, to industrial pollutants and now apparently fructose and cigarette smoke.

This makes any real solution to the "Diabetes epidemic" unlikely. Heavy manufacturers and big agriculture don't plan to stop polluting our water and air. In fact, they have become very skilled at evading existing regulations. Two thirds of the foods available in our supermarkets and fast food outlets are filled with fructose and transfat as well as thyro-toxic, autoimmune provoking soy--as well as a laundry list of chemical ingredients the average consumer cannot begin to identify.

The less money people have the more likely they are to eat the cheap fructose and soy filled foods available. When you have only two bucks for lunch and that will buy you a soy and fructose taco for $.69 and a soda, you buy it.

There's a movement to replace some of the corn syrup in our food with sucrose--which is still half fructose. Unfortunately, there is no movement to remove sugars from things like chicken dinner and soup.

Since most of us were eating the fructose-filled foods for decades before diagnosis, we'd all like to know what it takes to reverse the fatty build up in our livers. There isn't any clear answer on this. Lowering your carbohydrate intake and cutting down on fructose may not budge the fat that is already in your liver. Most of the people who are severely insulin resistant who eat low carbohydrate diets for long periods of time appear to stay insulin resistant.

There are a host of fraudulent "liver cleanse" products out there which do nothing but cleanse your wallet. Don't fall for them. Lemon juice does not magically remove "toxins" from your liver. The liver removes toxins from the liver since that is a big part of its job. But it doesn't seem to be able to remove the fats that clog its own tissue. Metformin may or may not help. Beyond that, who knows?

I'd love to hear from research savvy readers about any treatment you have seen where there is solid data, not paid for by a supplement manufacturer, that links a treatment with the reduction of liver fat and improvement in non-alcholic fatty liver disease.



Rishara said...

Michael Eades new book "The 6 Week Cure..." addresses liver fat and the relation with fructose consumption. I think he links the creation of visceral fat to the fatty liver as well. I've only read the first few chapters so far, but it seems to tie into your article pretty well.

Anna said...


Great post. Just a couple nights ago at a reception one of my husband's colleagues were talking about lovely Alpine Swiss butter and eventually the topic moved over to sugars. He said to me, "but fructose is the fruit sugar so it's ok, except when it's in soda". Arrrrgh. That's the sort of misguided claptrap I expect someone to hear at a parent/baby play group in the park, not at a gathering of preeminent scientific minds. Ok, his area of expertise is in a very different area so I'll cut him some slack (he studies development and functionality of hearts in fruit flies, actually), but still I was struck by what he didn't know about fructose and the damage caused by fructose. And he doesn't question the Lipid Hypothesis at all - he assumes it's been solidly proven that saturated fat is harmful, despite hailing from a European nation with a very high per capita saturated fat consumption and a rate of CVD that would make Americans drool. I've run into that a lot - these senior level "basic research" scientists just give their colleagues in cardiac, lipidology, hematology, and diabetes research the benefit of the doubt without question. I'm quite sure I was surrounded by Lipitor takers en masse that evening. Oh well, while the fat and meat-phobes were at the ravioli buffet, my husband and I had lots of elbow room at the salumi and European cheese buffet ;-).

On another note, have you had a chance to read the new book from the Drs. Eades? The 6 Week Cure for the Middle Aged Middle. The book emphasizes the unhealthy liver issues in particular. Their 6 week program seeks to address the fatty liver issue, especially in the first 2 week phase, to accelerate and promote fat burning. Their approach is also designed to spare protein so that the weight lost is fat, not lean mass.

Also, while reading your post I was reminded of the standard dessert my mom prepared once she became indoctrinated as a fat-phobe in the 1980s - angel food cake. Usually she bought the cake from the "bakery dept" of the grocery store (not homemade) and it was accompanied with something else sweet, like fresh strawberry sauce (with added sugar of course, or drizzled with fat-free chocolate syrup (or both). But you know, it had no fat, so it was ok, right? Yikes, I can feel my BG spiking just thinking about it, LOL.

And of course, the angel food cake was just one of many "approved" non-fat, high sugar foods that seemed like the ticket to avoid the dreaded CVD. No one ever suggested eliminating dessert, just the fat from the dessert had to go (oh wait, didn't Yudkin finger the sugar?). Of course, she's now T2 and underwent a double bypass in June...

Kathy W. said...

Here are some links on how diet, exercise, and weight loss affect liver fat (sorry for the long links!):

Jenny said...

A bunch of people on the Low Carb Friends forum are trying the new 6 week Eades diet. I'll know more about whether it is useful or not in six weeks.

The pitch annoys me--it sounds too hucksterish. Is is obviously being marketed as a quick fix, which sells a lot of books but doesn't do much for people's health.

From what I've heard the diet relies heavily on protein powder shakes which I consider unwise, along with various supplements.

I will hold off making any decisions about it until I hear feedback from a selection of people who try it.

Kathy W,

Thanks for the links. I'll have a look.

Kathy W. said...

Okay, those links came though broken. Here they are as tiny urls:

(this last is a pdf file.)

Anna said...

I've read the new Eades' book. I'm also not enthralled with the idea of quick fixes or protein powder shakes, either, even if they are "homemade" shakes and not an OTC just "add water" formula. I prefer real food an overall food philosophy. The multiple shakes per day part is only two weeks, though - 3 shakes a day (with varying amounts of protein powder in each shake, determined by gender/size), plus one "real" meal a day (doesn't matter which meal, can be at the dieter's discretion). Two weeks of these shakes are hardly the same as living on Slimfast or Medifast. The DAG oil seems like a very dispensable or discretionary component of the plan, and Dr. Eades as much said so recently in his blog comments (it was included because it was what they used when they needed to drop some pounds around the middle quickly for their TV show).

Another thing is the underlying research for this plan is based on essentially a mostly fat and meat diet for the first few weeks. The research was conducted nearly simultaneously in the 60s or 70s before anti-meat and anti-fat hysteria gripped everyone, by two different doctors in different specialties who weren't even in contact with each other. A "side effect" of the fatty meat diet (for other conditions) was loss of body fat without loss of lean mass. I'm the opposite though, I find the fatty meat diet a lot more appealing than protein powder shakes. I don't want to reawaken the sweet tooth dragon, either, now that I've kicked the sugar substitute/Splenda habit about 95%.

In this context, I can see why the Eades went with the protein powder shakes. Shakes are fast, easy, and while high quality protein powder is not cheap, the cost is reasonable and even non-cooks can manage them. There's not much variation in the macronutrients in plain protein powder, so the shakes well remain fairly standardized if the protein and carb per scoop guidelines are adhered to.

But try getting people to eat mostly fatty meat for two weeks these days. Hardly anyone will do it, for lots of reasons; it will seem too expensive, require too much effort cooking or shopping, takes too much time, is too boring, is socially or psychologically awkward, and so on. And the weight loss results might be less reliable, because the fatty meat that people might choose is highly variable; some might choose options that very different from what the diet program has in mind.

But I think you are right, it will be interesting to see how people fare on this plan as more people try it. The Eades say they had success with many patients who used this plan, but will book and blog readers have the same results? I'm curious too. My weight and BMI (22) are quite stable the past 3-4 years, but I did have a few middle aged middle fat pounds creep back on after my initial weight loss via low carb 5 years ago, which I'm quite sure is due to peri-menopausal influences. Even with my weight exactly the same as when I was about 30yoa, my shape and fat distribution is quite different - decidedly middle-aged. I see the same with my husband. One has to work harder to avoid tipping the fat/lean mass ratio while aging.

Terry Hilsberg said...


You have hit upon two issues of interest to myself.

Firstly, Whilst I am no biochemist, i was impressed with Dr Lustig's recent video in which he talked about the similarity of the impact of fructose and alcohol upon the liver. That is NAFLD appears to be basically the same as AFLD. I therefore asked Peter at Hyper lipid whether we should aggregate their effects and his answer was affirmative.

So, in your above calculations you should perhaps add alcohol intake. For many adults this would well and truly make up the missing ground that you note exists when just using a calculation of fructose intake.

My second comment is also about the use of protetin shakes in the Eades new book, in particular those based upon whey protein, which appears to have an insulinotropic response that is higher than milk itself. E.g in one study an increase in base fasting insulin response of >20% in eight year old boys from whey protein equivalent to an intake of 1.5L of skim milk, when compared with a control group who actually drank the 1.5L of skim milk.

(See Melnik, Permanent Impairment of insulin resistance from pregnancy to adulthood: the primary basic risk factor of chronic Western diseases, Medical Hypotheses, June 2009, which sets out the studies).

I intend to write to the Eades to ask about this.

benn686 said...

So if you were to replace all fructose with sucrose, that would be better?

I can't imagine that drinking raw fruit juices is bad... just ask jack lalane or jay kordich!

Jenny said...

Fruit juice has much more sucrose in it than fructose. You get maybe 3 g of fructose eating a whole fruit. Compare this with the 76 grams you may be getting in a 24 oz regular Pepsi. HFCS may contain up to 90% fructose.

And of course you are getting tons more fructose from HFCS in soup, bread, salad dressing, and a dozen other foods you wouldn't expect to find it in.

Anna said...

Also, one problem with fruit juice is that you are consuming the fruit sugars (glucose and fructose) of many times the amount of fruit you'd consume if you you were eating just plain fruit.

For example, I have a number of citrus trees in my garden including a Valencia orange tree (that's a variety bred for its juice). I have a hand-crank geared juice press that does a pretty good job of citrus juice extraction compared to hand-juicing methods (reamers, hand-squeezing, etc.). It takes at least 2 but usually 3-4 oranges to fill just a tiny juice glass (no more than 6 oz capacity). Anyone who still squeezes citrus fruit for juice knows it takes a lot of fruit to make a small amount of juice (which is why most people obliviously now buy pre-squeezed juice).

I never see anyone drinking only 4-6 oz of juice anymore, even in restaurants where juice servings tend to be somewhat smaller and more expensive than other beverages - it's usually more like 12-16-20+ oz of juice. That's a huge dose of sugars - glucose and fructose. No one eats that equivalent of sugar in whole fruit in one sitting.

My experience with fruit juice and my BG is to exercise extreme caution and stick to only juice I make myself and in amounts that would be reasonable to consume as whole fruit and still maintain good BG control. Usually I don't even consume juice as a beverage, but rather as a flavoring ingredient, so the per serving amount of juice (& sugar content) is very low.

And I keep any fruit content in smoothies very low, too, with the fat content high, plus some protein. That's been a difficult issue with my son, because his friends' parents love to treat the kids at the "smoothie bars" or fro-yo shops. Those places create smoothies that are sugar bombs the equivalent of sodas or even worse.