Thursday, September 16, 2010

Fathead, Supersize Me and Sweden

I generally ignored this paper in 2008 as it didn't look particularly interesting and seemed mostly about fast food bashing, where the fast food included a large amount of sugar and starch. A bit like a real life Supersize Me, but with genuine average food intakes provided and individual responses in ALT levels, a marker traditionally associated with liver damage, also provided.

If anyone wants to eat 285g of sugar a day then they deserve whatever they have coming to them. What they have coming is an ALT increase which correlates with either carbohydrate or sugar intake by three weeks in to the feast. Not with fat.

I found the lack of association with fat disappointing. Sweden is a country fairly replete with trans fat and a little arithmetic applied to Table 1 (LeenaS describes these as "hidden fats") suggests that trans fat intake went from about 6g/d to 24g/d during the over feeding period of the study. This is not quite at the level of Crisco poisoning but I was still disappointed to see no discernible association with ALT. Ah well, you can't have everything.

Now I remember Tom Naughton nuking himself with trans fats during Fathead to the point of lowering his HDL, but otherwise he developed no suggestion of metabolic syndrome. But then Tom engaged his brain before drinking bucket loads of fructose and desisted from such stupidity. The fructose trick is for anyone with more Spurlockian intelligence.

To go back to Sweden: Gross overfeeding with "fast food" elevates your ALT. This is sort of boring because no one in their right mind is going to eat that much fructose in a month, which sort of defines Spurlock.

But was anyone still awake by the end of Supersize Me? Remember how long it took him to lose weight on his girlfriend's vegan cooking?

Now the question is, does this translate across in to the Swedish ovefeeding group? Well that was answered by a follow on study looking at the participants two and a half years down the road.

They're still fat. On average.

Something breaks in a month of overfeeding with trans fats and sugar. That is fascinating. Now you could argue that the volunteers got the taste for junk food, that their fat cells got stretched, that they were already self selected for being comfortable with gaining weight to take part in the study etc. I'd like to look a little more closely at liver pathology.

Elevated ALT is traditionally assumed to indicate liver damage. But there might be circumstances where you make more ALT in each cell, especially if a lot of amino acid processing is going on, so get benign ALT elevation. No one had a liver biopsy so it was impossible to find out exactly why the ALT went up.

Now, from a pathologist's point of view, a fatty liver is completely reversible. There is nothing permanently damaged in each hepatocyte or in the structure of the liver. Hepatic inflammation is also theoretically reversible. Those old leucocytes can leg it out just as easily as they legged it in.

But fibrosis, that's a different matter. Fibrosis is there to stay. This is at the micro architectural level. We're not talking cirrhosis (yet). No pathologist expects a fibrosed liver to go back to normal. It may adapt, regenerate, keep you alive, yes. But it's not normal. It will never be normal.


I picked up a link to a mouse study in which they fed chow, Super Crisco (medium chain trans fats, what are they?) or Super Crisco plus fructose enriched sucrose via the drinking water. The rest of the diet is not in the abstract so who knows what else they did. But it was the Super Crisco plus fructose/sucrose in the drinking water which made all of the headlines.

Super Crisco appears to be bad for your waistline but may not, on its own, produce the irreversible changes in the liver seen in the mice who combined it with HFCS. As far as you can tell from the abstract.

A diet replete in trans fats and HFCS fibroses your liver.

Translating from the Swedish volunteers and these poisoned mice to our two film directors:

Tom Naughton should be fine with his low fructose high trans fat diet and Spurlock should have aged his liver by a few years (in terns of insulin sensitivity) during his month of self poisoning on trans fats because he combined them with fructose to push his ALT through the roof.

I'll try and put this in to a physiology context when a little more time comes my way.

Peter

BTW: A methodological note from the initial Swedish study which adds the "human element" to the mind set of the "scientists" running it:

"If the subject was not able or willing to ingest the hamburger-based diet at any stage, it was changed to whatever food the participant accepted with the highest priority to achieve the calculated caloric intake and also, if the study subject still found it acceptable, a diet rich in protein and saturated animal fat."

My emphasis.

As always, it's nice when people nail their colours to the mast.

I see from Table 1 in the follow-on study that one man and one woman had actually reduced their weight to below their pre study weight by 2.5 years. I just wonder whether they were the ones who refused the trans fats of the hamburger diet and went with animal fat and protein to source their excess calories. No one is saying.

That human element gets everywhere!

EDIT: See Patrick's notes in the comments about the group leader from the hyperalimentation studies. A different impression from the published papers. There is hope for Sweden. Good.

23 comments:

  1. Are you sure Tom Naughton ate trans fats in fathead? I thought it was just naturally occurring fats no? I can't recall he ate any, although its been a while since I've seen it.

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  2. Hi shell piece,

    I didn't think fast food outlets used non trans fats in the USA, but I would agree I too am working from memory as we have to switch a computer between DVD zones to view Fathead and we're running out of switch allowance! I really must get a decent DVD player. But Thomas the Tank Engine plays fine on the one we've got so I'm loathe to splash out in the immediate future.

    Peter

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  3. "Six- to eight-week-old male C57Bl/6 mice
    (Jackson Laboratory, Bar Harbor, ME) were grouphoused in cages in a temperature-controlled vivarium (22 6 2 C) on a 12-hour light/dark schedule at the University of Cincinnati. Animals were randomly assigned to a chow diet (Teklad; Harlan, Madison, WI), a high-fat (HF) diet (Surwit diet [58 kcal % fat]; Research Diets, New Brunswick, NJ), or a high-fat, high-carbohydrate (HFHC) diet (Surwit diet) and drinking water enriched with high-fructose corn syrup equivalent. A total of 42 g/L of carbohydrates was mixed in drinking water at a ratio of 55% fructose (Acros Organics, Morris Plains, NJ) and 45% sucrose (Sigma-Aldrich, St. Louis, MO) by weight. Animals were provided ad libitum access to these diets for 16 weeks. Body weights were measured weekly, and percent body fat was measured at 12 weeks using Echo MRI (Echo Medical Systems, Houston, TX). All animal experiments were approved by the Institutional Animal Care and Use Committee of the University of Cincinnati and Cincinnati Children’s Hospital Medical Center."

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  4. He didn't eat any of the fries, etc., and minimal desserts. One source of trans fats off the top of my head would have been in whatever biscuit-type breakfast sandwiches he might have been eating. I don't think transfats occur in cheeseburgers/buns.

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  5. Naughton's food log is online: http://fathead-movie.com/content/MyFoodLog.htm

    He doesn't have trans-fats broken out, but it looks like he usually discarded the breakfast muffin but ate the buns that came with other sandwiches. I'd guess there are trans-fats in the buns (why not?) and maybe in some of the salad dressings and condiments, but I'd further guess that he avoided most of them by avoiding the fries and muffins. He certainly would have eaten far less trans-fat (but probably more real fat) than Spurlock.

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  6. I have the mouse full text, thanks Jennifer

    I picked up some trans fat information here:

    http://www.ncbi.nlm.nih.gov/pubmed/19109659

    Peter

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  7. Peter, you can play European and US DVDs with the VLC player on your computer, no need to switch zones...

    http://www.videolan.org/vlc/

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  8. This comment has been removed by the author.

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  9. Any transfats in the 'special sauce'? It's first ingredient is soybean oil.

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  10. Peter,

    Thanks so much for finding time to post in between everything else going on. I've tried to look into the (brutishly simple) idea that fat gain and related ills are, like functional gut disorders, correlated with the consumption of many foods that: 1) have a proportion of fructose to glucose greater than 45:55; or 2) when consumed in one sitting, contain total fructose in excess of a limit (25g to 50g)? See here, for example.

    Are there any food combinations in which fructose in excess of these limits is OK? Or any in which fructose below these limits is not OK? I really can't think of any, though perhaps, no one has really controlled for fructose in this way?

    And is the implication that glucose/dextrose by itself is not nearly as bad as fructose?

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  11. Hi Peter,

    Look into flashing your dvd drive to make it region free. It carries a slight risk, of course, but then everything does.

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  12. From McD's website.
    So, yes there are transfats in the buns and HFCS! Same for most of their other menu offerings and condiments too.

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  13. As always, it's nice when people nail their colours to the mast.

    Fredrik Nyström is considering saturated fat as harmless (and carbohydrates as harmhul), at least in recent years.

    I think the wording reflects that the diet was trying to mimic the Spurlock diet.

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  14. Gunther and Kiran,

    Ta, I'll look in to this, might well be useful.

    Hi J A Deep,

    I'm suspicious that fructose, like alcohol, is possibly harmless in the absence of hyperglycaemia, PUFA or trans fats. It undoubtedly induces hepatic lipid production (and hepatic insulin resistance) but this is reversible once insulin drops and the liver starts shipping out VLDLs.

    It's also interesting to speculate whether fructose alone produces persistent hepatic damage. Still trying to get some papers on that one.

    Patrick,

    It would have been nice if he had commented as such in the discussion. And if the group had suggested the alternative to fast food as being food rich in sucrose and partially hydrogenated soyabean oil, with some meat added.

    That would have been more acceptable as a mimic of Spurlock.

    The 2.5 year follow on paper does mention that ALT was associated with carbohydrate intake but no link to the now fairly extenisve literature was made... A saturophilic carbophobe might have discussed this in either paper's discussion.

    BUT, if this research and the data it generated have changed his mind he then becomes a scientist without the inverted comas. That would be excellent as an outcome.

    Peter

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  15. Hi Peter,

    Thanks for your insight! You write, "I'm suspicious that fructose, like alcohol, is possibly harmless in the absence of hyperglycaemia, PUFA or trans fats." This is brilliant!

    Is there any reason to consider the converse? That hyperglycaemia, PUFA or trans fats are possibly harmless in the absence of fructose!

    Where by "absence" perhaps we mean fructose at no greater than the level (arguably) found in a non-autumnal paleo environment (45:55 fructose/glucose and no more than 25g at a sitting)?

    Is it possible that peoples the world over have survived nicely on every manner of diet, including hyper-glucocaemic (corn starch), PUFAs (insects, olive oil) and even trans fats (rancid fats) -- until the introduction of an unprecedented load of non-stop year-round fructose, i.e., Hyper-fructocaemia: the presence of an unusual amount of fructose in the bloodstream!

    Thanks again!

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  16. Peter

    Here you can read a short interview with Nyström i a Swedish newspaper:

    http://translate.google.com/translate?sl=sv&tl=en&u=http://www.expressen.se/halsa/1.1682062/sa-enkelt-slipper-du-dina-semesterki&act=url

    SATURATED FAT
    "In my fast food study, participants were not any significant increase
    of the harmful LDL cholesterol while most raised the good HDL cholesterol significantly. The more saturated fat they ate, the better the blood fats, they had."

    CARBOHYDRATES
    "In contrast, participants who ate the most carbohydrates in the fast-food study the worst liver values. The only sensible thing is to skip the carbs."

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  17. Patrick,

    That's excellent. He can lose the "marks" from scientist. If he could just get this message in to his publications... But a newspaper is a good place to be open, reaches the public. I stand admonished.

    J A, perhaps, but the omega 6s seem to be coming out badly w/o fructose in the stuff I'm reading at the moment, some of the time, depending on the model of course!

    Peter

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  18. Maybe this is fast food bashing but when you buy a meal at MacDonald's here in Malaysia (they call it a "set") you have to pay a bit extra to get a bottle of water instead of a cup of soda. I know what you may be thinking but sometimes one gets desperately hungry when traveling. Especially in a country where you can buy nothing from the freezer section that isn't loaded with "Approved flavor enhancer" otherwise known as MSG.
    So MacDonald's, who certainly can afford to pay attention to all the the nutrition research out there, would have us sucking down fructose rather than water. Question, does a bottle of water cost more to deliver than a cup of Coke? Can any of the corporate food conglomerates take even a moderation attitude toward pushing sugar at the unsuspecting masses? You got it Peter, a world gone mad.

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  19. If I'm understanding you correctly, you seem to be suggesting that liver damage sustained during hyperailmentation is possibly responsible for permanent changes in regulating body weight and maintaining a low body fat mass.

    I would disagree based on the observation that primary liver pathologies and liver damage does not cause weight gain problems. If damage to the liver contributed to fat gain (rather than being symptomatic of metabolic abnormality) then we would observe alcoholics and people with hep C having problems keeping their weight down and having diabetes and such. This really doesn't occur, and if it does occur it's usually related to some vitamin deficiencies and it's not the same animal as your garden variety obesity.

    Rather it seems to me that damage to our little chemist, the liver, is secondary to unnatural massive overfeeding of a sort that would never occur naturally. Overdosing on sugar and dietary fat and calories is not all that much different than taking 10,000 mg of acetominophen... some degree of liver damage is going to result. The liver can only handle so much. Liver enzymes are going to go wacky. How permanent it is is another question, but the rational conclusion is that damage to the liver is just a symptom of putting lots and lots of chemicals in it that don't belong in it. And as stated, an unnatural amount of force feeding is quite damaging to the liver like a big dose of drugs, since the liver needs to process it all regardless of whether or not it is food or drug.

    I would argue that the long term changes in regulating weight occurring to these people probably is related to the fact that obesity is a chronic disorder triggered by abnormal amounts of insulin which in turn is triggered by abnormal amounts and types of food. Some people are more sensitive to this than others are (I am very sensitive and even "normal food" is enough to trigger the process)... but I would argue whenever your body is exposed to very high levels of fatty acids, glucose, and insulin for a long period of time, you take the chance of fucking shit up. Permanently.
    You can get: mitochondrial damage and death leading to insulin resistance (so you will never again process food the way you used to and are now quasi-diabetic), insulin induced white adipocyte differentiation into mature adipocytes (which will permanently raise your set point much in the way growing an extra pair of hands will raise your finger # set point)... you can deplete your vitamin and mineral stores (as these are depleted by metabolism of glucose and fat if they are not replaced adequately) which will then exacerbate any acquired metabolic problems.

    I would argue changes like the above mentioned are the real reason these kids are finding themselves struggling with weight prematurely. They sped up their metabolic age by doing something as stupid as eating 2.5 times the amount of food their bodies asked for, for a very long time. It's not that much different than overclocking a CPU processor and wondering why the crap dies out on you. Or, running your brand new car into the ground and wondering why the engine is having problems.

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  20. Hi Its,

    These are things which occupy my thinking a great deal at the moment. Especially vinyl chloride exposure and chronic hep C, both of which are associated with peripheral (probably secondary to hepatic) insulin resistance. But not invariably with obesity. Trying to extract what is going on is fascinating. There's a lot more to consider.

    Interestingly tranisent ALT elevations are "associated" with the whole raft of the metabolic syndrome. But is that from incremental low grade incremental hepatic injury or simply chronic unremitting fructose abuse??????

    This all comes from whether hepatic insulin resistance is reversible (as in short term fructose metabolism) or irreversible (when fructose abuse, with other factors, leads to fibrosis).

    This has implication as to whether a sucrose/PUFA free diet can render you "normal" if instigated before your adipocytes and mitochondria get broken.

    It's an interesting area of speculation but getting convincing facts together is not proving easy. I'm not letting the concept go yet though.....

    Peter

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  21. Peter, you talk of elevated carbohydrate intake increasing ALT levels as if it is common knowledge. Sadly, from my experience, it does NOT appear to be commonly known by practicing doctors. Starting around 1998 (after years of trying to eat "low fat") I had increasingly elevated ALT (alanine aminotransferase). My physician made me quit drinking -- didn't help. Sent me to a liver specialist (at the University of Utah) who suspected fatty liver, and did a biopsy -- no fatty liver. In 2004 I read Protein Power and went low carb. Six months later my ALT was normal. My primary physician still does not believe the connection between carbs and ALT.

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  22. Peter, you know a lot more than me about the slippery subject of lipids, so fortunately for my own self-esteem I am actually able to correct you here on a point of no small importance: fibrosis of the liver is in fact reversable. Indeed, reversal of fibrosis - and even early-stage cirrhosis - is one of the end-point targets when treating (for example) Hepatitis C.
    Here is a review of the subject: http://www.hepatitistechnologies.com/images/reversal_of_hepatic_fibrosis.pdf
    And this study spells it out: "Conversely, the 102 patients who achieved SVR had a significant reduction in fibrosis
    score; 73 percent of patients who had portal fibrosis
    on their first biopsy showed no evidence of scarring on the second biopsy, while 20 percent showed no change with treatment. Of the patients with bridging fibrosis
    on first biopsy (52 percent of the cohort with SVR), 35 percent had no scarring on the second biopsy, 23 percent had portal scarring, 38 percent remained unchanged and 4 percent had cirrhosis, which investigators believe could be a sampling error [yeah right! These drugs do damage the liver sometimes - GDH]. For patients with cirrhosis on first biopsy (19 percent of the cohort with SVR), 50 percent had improved on second biopsy — 10 percent had no scarring, 10 percent had portal scarring and 30 percent had improved to bridging fibrosis."
    (Richard Sterling, MD, MSc, Professor of Medicine, Virginia Commonwealth University, quoted on http://www.medhelp.org/posts/Hepatitis-C/New-study-presented-at-DDW-re-fibrosis-reversal-after-SVR/show/966068)
    Also, and perhaps of interest to you, there are Nanji's wonderful studies showing that beef fat can reverse fibrosis in alcoholic rats.
    Amin A. Nanji has been proving the worth of PUFA restricted, high SFA diets in models of liver disease for decades, and his work deserves to be much more widely known.
    for example: jpet.aspetjournals.org/content/299/2/638.full.pdf
    I wanted to correct this as people with fibrosis can become fatalistic and continue damaging their livers if they get the message that the damage they've already done is irreversible.

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  23. There are reported instances of reversal of fibrosis/cirrosis of the liver: http://www.hepcprimer.com/biopsy/biop-rev.html

    I'm on a low carb diet, and prior to that was observed to have what appeared to be a fatty liver on and ultrasound examination. I am making a point to have liver once or twice a week and drinking green tea, which I am hoping will help. Does anyone know of any other treatments?

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