Some thoughts on fructose studies

I've been poking about the literature lately ever since the insulinogenic (in terms of circulating insulin levels but not necessarily secretion of insulin) properties of jelly beans were made known to me a while back.  I've been looking into studies comparing sucrose to glucose or fructose separately, or that measure insulin secretion and/or clearance per se.  It's a rough go.  Much of the research that turns up with fructose in the search phrase involves HFCS not fructose per se.  When you get isolated fructose studied, however, there are still other complications. 

For starters, it is impossible to isolate the effect of just fructose with whole foods.  Just about every source of fructose, like fruits, also contains sucrose and even considerable amounts of isolated glucose in many cases.   It is also virtually impossible to attain the levels of fructose generally required to elicit a measurable metabolic response.  For reference, a medium apple contains roughly 10g fructose (most of which is free).  A "bolus dose" for 50g would be difficult to achieve and would come with ~5g glucose per apple.  So ... sweetened beverages it is as the major dietary vehicle by which fructose is incorporated into dietary interventions.

To be fair, this is how many Americans get their excessive fructose.  To those I would summon my best Katie Couric valley-girlish "DUH" and say just stop drinking the crap!  Really, where on the USDA food pyramid or MyPlate or anywhere else has the government or any nutritional organization EVER promoted mass consumption of sodas and other SSB's??   I'm not talking ads by sugar producers, etc.  I'm talking nutritional advice.  Please prove me wrong, but in my lifetime, during which Frosted Flakes used to be called Sugar Frosted Flakes, I don't recall anyone from my pediatrician, to my dentist, to my school nurse, to my health teacher, ever advising me to eat them.   Indeed I can remember these being demonized as poor choices for as long as I can remember.   Sweets are up there with the fats and oils atop the old pyramid.   The only advice I've ever received vis a vis sugar from any authority figure has been to limit, limit, limit.

But it gets worse.  Far too many fructose studies are done in the context of hypercaloric intake -- in other words energy surplus.  The study by Havel's group that Taubes cited recently being one such case.  The subjects not only consumed roughly 150g of fructose for 10 weeks, they did this without compenstion for calories from ordinary intake so that they ate like 300 cal/day more than their energy stable intake.  That's 15 apples for anyone keeping track.  I came across another study recently:  Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes.  In this study they took male offspring of T2's and controls with no family T2 history, and fed them (in random order at different times) either an isocaloric diet (normal) or a hypercaloric high-fructose diet -- this diet was a +35% energy intake in fructose!  Now, granted "overconsumption" was in the title but ...

Now, as Taubes pointed out in his 2002 NYT article, we Americans DO consume more calories than we did in the 70's, and we also consume a lot of those calories in sodas and such.  Not because, as he absurdly suggests, our government and nutrition authorities are sanctioning them as "low fat".  So the overconsumption studies are pertinent to "real life", but they are demonizing a nutrient based on a pathologic eating scenario.  The result is that we're going to spawn a generation of fructophobes who will eschew even fruits.  In our search for the mythical singular cause of all obesity, we're going to finger sugar.  Taubes even says now that we could probably eat all the pasta, bread and rice if only we lay off the sugar.  That's the secret of the Japanese!   He heralds the research into sugar as the devil as being some of that "good science" that's been missing and a few are now doing (at his urging of course).  

Unfortunately, though some of these studies are pertinent to a segment of the population who guzzle SSB's, they are wholly not applicable to the real life scenarios in which most become obese.  I'm not alone in having gotten obese never drinking a regularly sweetened beverage since my mid teens. Sure you have the soda junkies consuming massive amounts of liquid calories and not compensating for solid food calories, but this is not the majority of the population.  If it is, the solution is simple.  Outlaw soda and juice "drinks".  He he .. the libertarians occupying the Insurgency aren't going to like that ;-)  But seriously, limit sweets in general has been around for a long time.  Nobody in their right mind believes the uptick in sugary beverage consumption was because said beverages were low fat.

The other problem with all of these studies is that they separate the fructose from the other things in foods that contain it.  I'm not just talking about the fiber, which is one factor, but fructooligosaccharides (FOS, classed a fiber but no the apple peel type of fiber we usually refer to), vitamins, minerals, phytosterols and such.  At least give real juices a fair shake in this that at least contain some of the "go withs" that are absent from most SSB's.  And on that topic, who knows the contribution of the flavorings and other additives.  These studies usually use flavored beverages, but many recognize plain sugar water is not all that appealing.

So, I'm afraid that in general, I would hang a "bad science" tag around the necks of most fructose researchers.  Not because it's all bad, but on the whole a lot of the studies have limited application to real life scenarios.  To keep some inner city kids from buying a 2L generic cola for a buck, politicians would like to slap an "only few cents per liter" tax on the stuff.  Treat fructose like alcohol and tobacco.  I'm sorry but I'm not the most libertarian person out there, but I'm not the most socially engineering inclined person either.  I think such taxes will only produce more revenues to be pissed away spent on wholly unrelated pet projects while having minimal impact on the consumption behavior and health of the supposed targets they are trying to help.  And to me this is where this science is dangerous.  Because the title of a paper Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes, becomes the headline like:  Sugar consumption causes fatty liver. 

Not sure there's a summary message to this post other than just to "talk out loud" a bit about the state of the science in fructose research.  I keep hearing a lot of misinformation repeated about it -- e.g. that it can't be metabolized for energy so it is all turned to fat, that it raises triglyceride levels because of that, etc.  This has caused some to say we should never eat fructose at all, and at the extreme, for the likes of Lustig to unequivocally deem it a poison with no positive purpose in our bodies.  I think eliminating all fructose just because a 2L bottle of Coke a day habit is not good for you would be as silly as avoiding eggs for fear of raising your cholesterol.

Comments

Tonus said…
Not to take this in a political direction, but my concern over any government-led attempt at controlling how we eat is that you very quickly find yourself in The Land of Best Intentions. Tax sugary sodas? No problem, don't drink them anyway. Wait... you want to control my salt intake, too?

Pretty soon you've got a list as long as your arm detailing how you should eat (including salt restrictions pushed by a Mayor known to sprinkle salt liberally on his already-too-salty foods). But no, we won't outlaw cigarettes...

As ever, the problem with humankind is people.
bentleyj74 said…
Agree 100%

Heck, iron will kill you deader than a doornail if you over consume... it won't take years either but who within the context of even the dread SAD will hit that mark by eating food?

People with food/family dynamic/lifestyle dysfunction aren't fixed by well meaning but naive mass intervention efforts.
bentleyj74 said…
Just for the purpose perspective...

My H works in law enforcement so he gets up close and personal with where people are "at" when intervention becomes a consequence rather than a desire.

I can just see his response to telling the single mother who has just permitted her drug addicted well documented child predator boyfriend to put her children in the dryer and turn it on for "fun" that everything will be fine if she stops drinking soda. Pathology indeed.
LeonRover said…
Couple of points, Evelyn.

Alcohol and tobacco are RESTRICTED to adults - and Lustig is primarily a paediatrician. In addition, Lustig does believe in "An apple a day, etc.". He just do not believe in "fruit juice". Those damned Florida citrus growers!!

The sooner HFCS producers are made return to good ol' invert sugar, the better. How can one have pecan pie made with HFCS - it a'int nature's way.

As regards "bad science" - to quote John McEnroe "You cannot be se-ee-rious!!"

Knowledge is knowledge. Also recall Matthew "The devil can quote scripture for his own purpose" ie "The journo can quote from a study for his purpose".

Not "bad science" but "bad journalism".


This Lausanne paper by Swiss researchers, is an excellent piece of work on how to cause NAFLD, namely, feed the clients about 200 gms fructose per day for 7 days, and symptoms begin to appear, including fatty buildup in muscle tissue as well as liver. I wish many US studies were as well presented. It does not answer the question whether the same effects would occur on a dose 100 gms per day for 14 days or 21 days or .. or .. or. These would be new studies, and were they to be performed, would better simulate some real life behaviours.

I would have liked to have this same study done, but with an "alcohol arm" in parallel with the "fructose arm" and compare NAFLD with ALFD. Now that would be interesting.

"And I'll end up my days drinking Whiskey Galore,
Singing Bainne na mBo is na Gowna,
It's the Juice o' the Barley for me."

Slainte
Anonymous said…
New Here. Love the blog. As a low(ish)-carbohydrate dieter, It's great to have a place on the web to talk seriously about low-carb (a la John Yudkin) as a legitimate weight control technique, rather than a religion or an excuse to overeat. That said, I have to come to Lustig's defense here.

1. Lustig is not a low-carber and he doesn't even say we should not eat fructose at all. As much as he gets carried away and can be a bit of a loose cannon, he never said to avoid fruit. He answered the question of fruit in his lecture that fruit was self limiting and unlikely to cause problems in doses typically consumed. He said in a TV interview that fruit has a fraction of the fructose of SSB's, and fructose is difficult to get in large quantities without being refined.

2. As a poison, he compared fructose to alcohol. Not arsenic. His point being that problems come when you have chronic overconsumption.

3. Lusting also made clear that he views SSB's as responsible for the current obesity epidemic. Not obesity per se.

I think you're generalizing your own eating patterns to everybody when you discount the impact of SSB's. I'm friends with a pediatrician who treats inner city kids, and she can attest to Lustig's claim that kids today are drinking massive quantities of SSB's. I will however freely admit to having a personal stake in this issue. I've been obese since the age of five. My parents started giving me apple juice as soon as I was too old for baby forumla. It was my main source of fluid until I was as least 10 (I couldn't tolerate milk). Despite getting constant lectures about needing to go on a diet, nobody in my family ever took issue with my drinking juice except my grandparents. I remember that whenever I asked my grandma for a glass of juice, she would give me a five-ounce juice glass(hey, remember those?) and only fill it half way. I could never figure out why she would be so stingy with something so "healthy" and fat-free to boot. My own experience with dieting is that weighing less than 330 pounds has never been possible with fructose consumption greater then what you'd find in 3 or so glasses of orange juice a week plus all the stuff hidden in dressings and the like. Is sugar inherently obesogenic or just a huge source of unneeded calories? I have no doubt that the primary problem with it is the latter. I still wouldn't discount the former.
"Lustig is not a low-carber and he doesn't even say we should not eat fructose at all." I think I remember from watching a few videos of his various talks he set the "safe" threshold for consumption of fructose at 50g or less.
Tonus said…
As I recall, Lustig felt fruits were better than soda or fruit juice because they don't have the added sugar and because they also contain some fiber, which he felt we generally do not get enough of in a typical day.
CarbSane said…
Points well taken ...

With regards to kids and SSB's, yes, I've no doubt that consumption among some groups of kids is through the roof. Lustig seems to be a big proponent of taxes and such. Here in my state they've been tossing this idea about, but nothing as draconian as the taxes exceeding the cost of the product itself (as it now is with cigarettes, and I consider that to be abusive predatory taxation). Not a big fan of this and it won't fix the problem in that most of these kids are from single parent poor households with little supervision. My husband sees it every day where he works, I saw it regularly when I used to ride the subways when I taught in NYC a few years back. Children the same age as those who are not allowed to walk to school in my neighborhood are riding the subways alone or with an older sibling. That kind of autonomy was unheard of in my day and it is huge. Taxing SSB's isn't going to do a thing about this.

Yes, I'm huge on not blaming the scientists when the journalism is the problem not the studies ... but in the fructose arena it does appear that the scientists themselves are often not diligent enough in either realistic study design or presentation of the data itself.
CarbSane said…
Welcome to the Asylum -- I'll call you 26!

Lustig may not be a low carber, but he is becoming increasingly associated with this niche and does not appear motivated to distinguish himself from the insulin theories. While he is anti SSB's, does set a threshold as FTD points out, etc., all of that seems to get lost in translation with his overarching message: fructose = poison. And when he exempts fruits from that a lot of selective listening goes on in LC circles. I admit my opinions of Lustig are heavily clouded by his poor performance in comments on Alan Aragon's blog. (Google aragon lustig and fructose and I'm sure you'll find what I'm talking about)

I think sugar's role in obesity is largely that "latter" -- excess calories -- more and more in processed foods. It also, with carbs, makes some fats super tasty. Think ice cream! We don't seem to sense liquid calories well in general.

BTW, I'm in complete agreement with Lustig about one thing. Want to prevent obesity in children? Don't let them drink calories except for a glass of milk (low or non fat is fine with me depending on the rest of the diet) except on rare occasions.
LeonRover said…
Selective listening is the fault of the hearer, not the speaker.
CarbSane said…
While I would agree in general, this does not let the speaker entirely off the hook. Especially when the speaker is somewhat encouraging the audience to hear only what they want to. Don't know if that makes any sense, but some very nefarious figures have been able to garner fawning support through their verbal eloquence. If you dissect what they say, they often tell you point blank how they really feel and what their true motives are. Still they know certain audiences will never pick up on that and will take home the talking points highlights. I generally come down on researchers sides on this because I don't think you can hold them ultimately responsible for how lay people etc. will interpret their results. However, they have to be cognizant of what's going on and the potential for their work/conclusions being taken out of context.
LeonRover said…
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LeonRover said…
I agree with your penultimate statement unmodified by your ultimate one.

Matthew, again: "He who has ears to hear, let him hear".
P2ZR said…
I was so excited--I thought this would be another extensive fructose post, like your synching your posting schedule with Paul J's...but maybe good thing it's not, so I'm forced to chew through things first.

I'm surprised by how unequivocally he came out against fructose. Definitely wasn't expecting him to renege on his position--but he's clarified his position to be a Lustigian 'fructose = poison' one. It's one that fails to address why some PHD commenters and others in the blogosphere (myself included) have reported feeling amazingly better after consuming some fruit. I almost feel like there's something magical about its liver glycogen-replenishing properties. And I'm not one for superstition.

(Despite the last sentence...) I'm becoming persuaded that the adrenal fatigue phenomenon exists, and explains my feeling like abject and total sh*t when I fast (history of AN and coffee/EtOH overuse). And after a normal fast-breaking meal (after which I will still feel like sh*t), it is sugary FRUIT that makes me feel better. Not more starch, or eating rice syrup (which I have tried), which help only a tiny bit, but FRUIT. I don't even love the taste of fruit (and I'm talking palatable *dried* fruit!), but it has the ability to knock my body out of emergency mode like nothing else. (And if by any chance there's a LC'er reading this suggesting protein/fat instead--a huge 'F* YOU' because those only aggravate the problem.)

Don't see why Paul categorically refuses to entertain the idea of a U-shaped benefit/harm curve for fructose, outside the context of athletes. I think it's a very legit topic of conversation, even if the testiness that has just barely come through in his post would suggest otherwise. You *will* be addressing fructose more, right? ~minor prod~ I'm hoping that Stephan will also tackle it at some point, though I'm guessing that he occupies some sort of middle ground that is no man's land in this (emerging?) fructose war, and he probably doesn't need any more grief visited on WHS from either fructophobes or Peat-atarians.

Sorry, musing aloud....
P2ZR said…
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Keenan said…
If this is the study you are talking about http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0CC8QFjAB&url=http%3A%2F%2Fwww.ajcn.org%2Fcontent%2F89%2F6%2F1760.full.pdf&ei=RrIkT-rTG4GviALZxZmECA&usg=AFQjCNFViPgALNK4OCcsNTXnwesH73lJPQ I would hardly call it a excellent piece of work. They overfed 35% of calories with fructose and the diet was 30% fat(the fat source is unspecified so it could be soy oil for all we know).
Keenan said…
Ray peat's articles and newsletters on fructose are a wealth of info for anyone who's not quite convinced about fructose consumption, he has tons of sources and anecdotes
Keenan said…
Don't forget about the negative effect of PUFA on glycemia. Most studies tend to use fats very high in PUFA in these studies which obviously skews the results.

Accute effects of fatty acids on insulin secretion-
Fatty acids (0.5 mM) acutely stimulated insulin release from rat islets of Langerhans in static incubations in a glucose-dependent manner. The greatest effect was seen at high glucose concentration (16.7 mM) and little or no response was elicited at 3.3 or 8.7 mM glucose. Long-chain fatty acids (palmitate and stearate) were more effective than medium-chain (octanoate). Saturated fatty acids (palmitate, stearate) were more effective than unsaturated (palmitoleate, linoleate, elaidate).

http://www.ncbi.nlm.nih.gov/pubmed/8721768

LA diet-
Fasting blood glucose and insulin levels were significantly higher on the linoleic acid diet compared with the oleic acid diet (P < 0.01 and P < 0.002, respectively). Plasma cholesterol and LDL cholesterol levels were also significantly higher on the linoleic acid diet (P < 0.001). Likewise, fasting chylomicron apo B48 and apo B100 (P < 0.05) and postprandial chylomicron and VLDL apo B48 and B100 (P < 0.05) were also higher on the linoleic acid diet.

http://care.diabetesjournals.org/content/23/10/1472

Dietary supplementation with n-3 fatty acids may impair glucose homeostasis in patients with non-insulin-dependent diabetes mellitus.-
"The blood glucose concentration tended to increase during MaxEPA treatment, and to decrease during the placebo period, the changes under the two regimes being significantly different (P less than 0.01). In addition, the rate constant for glucose disappearance (k value) for the intravenous insulin-tolerance test, which reflected the peripheral insulin sensitivity, tended to decrease during MaxEPA treatment and increase during administration of the placebo, there being a significant difference (P less than 0.03) between the changes during the two treatments."
http://www.ncbi.nlm.nih.gov/pubmed/2394967

O3 deteoriates glycemic response-
"Average blood glucose concentrations during the third week were significantly higher fasting (+ 15%, p < 0.01), and during the day at 1100 h (+18%, p < 0.001) and 1500 h (+ 17%, p=0.002) on PUFA than on the saturated fat diet."

http://onlinelibrary.wiley.com/doi/10.1111/j.1464-5491.1992.tb01748.x/abstract
Gys de Jongh said…
Here is a recent article which differentiates between sources of fructose and compares energy-restricted diets.

Metabolism. 2011 Nov;60(11):1551-9. Epub 2011 May 31.
The effect of two energy-restricted diets, a low-fructose diet versus a moderate natural fructose diet, on weight loss and metabolic syndrome parameters: a randomized controlled trial.
Abstract
One of the proposed causes of obesity and metabolic syndrome is the excessive intake of products containing added sugars, in particular, fructose. Although the ability of excessive intake of fructose to induce metabolic syndrome is mounting, to date, no study has addressed whether a diet specifically lowering fructose but not total carbohydrates can reduce features of metabolic syndrome. A total of 131 patients were randomized to compare the short-term effects of 2 energy-restricted diets-a low-fructose diet vs a moderate natural fructose diet-on weight loss and metabolic syndrome parameters. Patients were randomized to receive 1500, 1800, or 2000 cal diets according to sex, age, and height. Because natural fructose might be differently absorbed compared with fructose from added sugars, we randomized obese subjects to either a low-fructose diet (<20 g/d) or a moderate-fructose diet with natural fruit supplements (50-70 g/d) and compared the effects of both diets on the primary outcome of weight loss in a 6-week follow-up period. Blood pressure, lipid profile, serum glucose, insulin resistance, uric acid, soluble intercellular adhesion molecule-1, and quality of life scores were included as secondary outcomes. One hundred two (78%) of the 131 participants were women, mean age was 38.8 ± 8.8 years, and the mean body mass index was 32.4 ± 4.5 kg/m(2). Each intervention diet was associated with significant weight loss compared with baseline. Weight loss was higher in the moderate natural fructose group (4.19 ± 0.30 kg) than the low-fructose group (2.83 ± 0.29 kg) (P = .0016). Compared with baseline, each intervention diet was associated with significant improvement in secondary outcomes. Reduction of energy and added fructose intake may represent an important therapeutic target to reduce the frequency of obesity and diabetes. For weight loss achievement, an energy-restricted moderate natural fructose diet was superior to a low-fructose diet.
Copyright © 2011 Elsevier Inc. All rights reserved.
PMID: 21621801

Gys
. said…
Is the metabolic syndrome caused by a high fructose, and relatively low fat, low cholesterol diet? -> http://www.ncbi.nlm.nih.gov/pubmed/22291727