Why Fructose is NOT Like Alcohol

Where did this come from?

Beginning with his viral YouTube video (I won't link to it, every additional view is one view too many!), and continuing on, Dr. Robert Lustig has been making the claim that fructose is metabolized like alcohol by the liver.  You cannot make your misinformation more clear than to title a section in your book as Lustig did in Fat Chance --  Fructose versus Ethanol:  Pick Your Poison.

Before Lustig, I don't think I'd ever heard anyone equate sugar to alcohol on a metabolic level.  A few may have made an addiction analogy, but it was Lustig who "taught" us the "science" that the liver processes sugar just like alcohol.

It is shocking to me that his video was produced and distributed by an institution of higher learning as a "Mini Medical School for the Public" presentation.  This implies to me that the content has been somewhat vetted.  Apparently it has not been, and also, nobody within that establishment has ever seen fit to correct the record?  Again, apparently not, as there is that Skinny on Obesity series out there repeating many of the previous errors.

The first time I watched the YouTube video my BS detector was going off left and right, remaining pegged on overload for long stretches.  It should have been for many in this community as well.  Every doctor, every nutritionist, and everyone who has ever taken a biochemistry class.  Heck, I'm pretty sure I read diet advice in Glamour and Self magazines in the 80's that was more scientifically correct than Lustig's video.


Maybe nobody pointed this out?

Ah but many did!  It seems to be status quo to ignore anyone with even the slightest taint of "mainstream nutritional thinking" and dismiss anyone with ties to the sugar industries no matter how factually and science-based their counterpoints are put forth.  But even Dr. Richard Feinman's call out was met largely with dismissal from those in the community for whom Lustig's popularity is of more benefit to their bottom line ... to heck with getting the basics correct.  Feinman writes:

The presentation of the science is compelling but, while it has a number of important points, it is clearly biased and, oddly, a good deal of it is totally wrong, some of it containing elementary errors in chemistry that border on the bizarre — how hard would it have been to open an elementary organic chemistry text? In trying to draw parallels between alcohol and fructose, Lustig says “ethanol is a carbohydrate.” Ethanol is not a carbohydrate. A horse is not a dog. If you said that ethanol is a carbohydrate in sophomore Organic Chemistry, you would get it wrong. Period. No partial credit.

Feinman made the following statement which is very similar, if not the same, as what I've been saying (and extended to the science underpinning low carbohydrate diets and the "experts" that promulgate it):

Such elementary errors compromise the message and raise the question in what way Lustig is an expert in this field.

Exactly!  In a way, it's not so much the "expert" label anymore, but a matter of whether one can consider the person a reliable source.  There's no way, that I can fathom, that someone with Lustig's educational background has gotten the basics of organic and biochemistry wrong, and that leaves folks with uncomfortable explanations for why he says what he does.  I can't believe that he seriously believes that (1) ethanol is a carbohydrate, or that (2) there are meaningful parallels between the metabolism of fructose and ethanol.  He is surely aware of the criticisms of him on the internet, so on the slim chance that he did make a mistake, he has had ample time to correct it.  Thus, I believe it brings into question what is motivating him at this point, and that is a fair questioning.


How fructose and ethanol are metabolized:

The image below (direct link) is a pretty good one demonstrating the metabolic pathways for fructose and glucose in the liver.

My only argument might be to stress the relative fates of AcetylCo-A ... The CO2 path (oxidation through Krebs/TCA) is quantitatively greater than the formation of fatty acids by de novo lipogenesis.  Still, does this look anything like the metabolism of ethanol at right?   Didn't think so.   Acetate is converted to AcetylCo-A and the various metabolic fates thereof are similar to fructose ... and glucose ... and theoretically fatty acids, though the metabolic milieu when excess fatty acid derived AcetylCo-A is formed favors ketones vs. DNL.  I suppose someone with no chemistry background might notice the "aldehyde" in common but these are distinct compounds and intermediates in unrelated pathways.

Further, the normal metabolism of ethanol produces an intermediate, acetaldehyde, that is toxic to the human body (moreso than the ingested ethanol).  The normal liver has limits in how much and how quickly this intermediate is converted to acetate for further metabolism, and acetaldehyde can exert toxic effects even when alcohol consumption may not be all that high (this is apparently quite variable).  If there are any intermediates that are toxic in the metabolism of fructose, they are not implicated as so in physiologically meaningful contexts.


Fructose is still converted to fat, right?

Well, some, but it is not known or overlooked that roughly half of fructose is converted to glucose.  The role of de novo lipogenesis has been covered pretty thoroughly elsewhere.

source

But ... The liver!

Many have claimed that because fructose is shunted to the liver for processing, it is by default a toxin as that is the liver's function.  This is clearly overly simplistic because the liver has many roles in the body.  I would argue that handling of toxins is secondary to the two primary functions of maintaining circulating glucose and fatty acids (NEFA) levels.

The liver's role in glucose regulation is sometimes presented as clearing a toxin, but this is plain and simply incorrect and misleading.  The liver plays a much more pivotal role in adding glucose to our bloodstream than removing it.  It works tirelessly to maintain a minimum glucose level and only produces too much in dysfunctional states.  The liver's role in NEFA regulation is a negative one, so does that mean fatty acids are toxic?  Well, actually they are, in excess, and the liver plays a critical role in repackaging them back up when more than are needed have been released into circulation.  The liver also repackages other fats -- dietary fats even.  So it removes chylomicron remnants and sends them back out as VLDL.   The liver is the only organ that does this.  By the "because the liver does it" logic fats are toxic!

Oh but we're talking about dietary compounds!  Oh yeah?  Well then perhaps you can explain to me why it is that coconut oil and MCTs are so revered in this community?  Because these, like fructose, have no function in the human body.   To the extent they make it into body fat it is likely by accident, they do not make up any component of cell structure, etc.  So they are metabolized in the liver to AcetylCo-A and ketones.   Would this not make them, by Lustig's definition, poison?


Are you advocating the Coke diet now?

No, but I feel I have to repeat this because that seems to be the retort to any criticism of fructose alarmism these day.  There are even folks that limit fruit on the basis of this argument -- that it contains fructose and fructose should be kept to a minimum or there will be metabolic costs to pay.   This is in stark contrast to the results seen in Lynda Frassetto's study:  Metabolic and physiologic improvements from consuming a paleolithic, hunter-gatherer type diet.  I wrote about the diet used in Is This Your Paleo Diet?   This was a short and small study, and lacked a proper control group, but the results were quite astounding.  I've highlighted a couple of things here:

We performed an outpatient, metabolically controlled study, in nine nonobese sedentary healthy volunteers, ensuring no weight loss by daily weight. We compared the findings when the participants consumed their usual diet with those when they consumed a paleolithic type diet. The participants consumed their usual diet for 3 days, three ramp-up diets of increasing potassium and fiber for 7 days, then a paleolithic type diet comprising lean meat, fruits, vegetables and nuts, and excluding nonpaleolithic type foods, such as cereal grains, dairy or legumes, for 10 days. Outcomes included arterial blood pressure (BP); 24-h urine sodium and potassium excretion; plasma glucose and insulin areas under the curve (AUC) during a 2 h oral glucose tolerance test (OGTT); insulin sensitivity; plasma lipid concentrations; and brachial artery reactivity in response to ischemia. 

 The study diets are shown below:

Now I would agree that this diet differs a bit even from that used in other studies and in practice (the carrot juice and low salt tomato soups 2X per day each), but it is important to remember that there was one week on the ramp up diets that included orange juice and then 10 days on this version of the paleo diet.  Breakfast of honey, carrot juice, pineapple and pork tenderloin!

Unlike some other paleo studies, this one ended up involving increased caloric intake of around 300 cal/day, about 14% over baseline totaling roughly 2700 cal/day.   It is rather difficult to dismiss the fructose in this diet in that cantaloupe and pineapple are very juicy and sweet and honey, why that has free fructose in it! The other notable change in the diet was an approximately 85% increase in protein intake from just over 100g to almost 200g.  The absolute fat and carbohydrate intakes were virtually unchanged (-5g carbs, -3g fat).  Given that the only significant starch comes from parsnips, this diet is fairly described as high fruit, and it is higher in fruit than the SAD (though not necessarily higher in fructose as that depends on the version of the SAD).

If fructose were alcohol ....


But fructose is not fructose!  Sugar is like cocaine because it has no fiber!

There are differences in fructose's effect on the body depending on the "packaging".  This is food for thought, and was discussed a bit here:  If you drink OJ, might it just as well be Orange Crush? 

Here's something to consider.  Let's say you were to feed 50 people 5 ingredient Cocktail A for 6 weeks, and then feed these same 50 people (in randomized crossover fashion as to which cocktail they got first)  5 ingredient Cocktail B for another 6 weeks.  And let's say that the only ingredient that was the same in both cocktails was Substance X.  At the end of the 6 weeks you measured a bunch of metabolic markers.  Now if Cocktail A caused metabolic mayhem while Cocktail B showed some minor improvements in those same markers, what conclusions might you draw?  If Substance X were fructose, apparently you throw the scientific method out the window and blame the fructose.  But hopefully the answer would be that it must be something about one or more of the other 4 ingredients in Cocktail A that is causing the problem, and/or something about one or more of the other 4 ingredients in Cocktail B is responsible for some improvements.  Fructose is not the problem.

Fructose is fructose.  It looks like this.  It is the same if it comes from honey, or fruit, or white table sugar.  It is the same if it comes from HFCS.  This is not to say that if you eat oranges, you might as well just drink orange soda -- exactly the opposite.  It's to say that if you consume fructose the package seems to matter more than the chemical itself.