Friday, October 14, 2011

Crisco and Cocaine, or A Fun Saturday Night

As usual there is a stack of papers awaiting my attention, but Dr. Aaron Blaisdell just tweeted this sparkling brand new one that just couldn't be ignored -- A History of Bingeing on Fat Increases Cocaine Seeking and Taking.  (Boy, rodent researchers really know how to make an intriguing combination of industrial lubricants "heart healthy vegetable oil" and cocaine sound boring.)

Song - an oldie but a goodie - The Dandy Warhols:  Bohemian Like You (right click to open in new tab)

I've discussed the rodent bingeing literature before:  see here and here and a little bit here. Rats and mice, like humans, will binge on sugary snacks.  Unlike humans, rats and mice will binge on Crisco alone, whether it is the old fashioned trans-fat kind or the modern however-it-is-they-make-vegetable-oil-solid-at-room-temperature kind we can buy in the supermarket now.  The sugar-fat combo seems to be the most damaging - though in all of these studies, a variety of vegetable oil was the fat used, so it is hard to know whether it is an omega 6 thing or a fat thing in general.

A little reminder - not all binge-eaters are obese, but 67% of them are.  And not all obese people are binge-eaters, far from it.  It seems that about 1/3 of those who seek medical treatment for obesity have binge-eating behavior, however.  If we are considering the prospect of disordered "food reward" pathways, perhaps looking at binge-eaters will help us to understand one extreme of the continuum.  Or perhaps the pathology behind binge-eating and the supposed disordered food reward leading to obesity are really different concepts.  I suspect they aren't entirely separate, but it isn't a simple comparison, either.  And certainly, exploration of binge-eating and addiction can hopefully inform our treatments of those disorders.

In this new study, researchers added the interesting twist of seeing if a history of fat-bingeing made their rodents more vulnerable to becoming addicted to cocaine in the future.  As I've noted from my clinical experience (and as is noted in the literature), binge eaters can (but don't have to) have a hard time controlling behaviors in several areas - bulimia and binge-eating often occur together with substance abuse in humans.  

Let's start with what all the folks agree upon - massive doses of sugar (really, sugar - sucrose, meaning glucose + fructose) are a bad idea, particularly in those who are vulnerable to addiction of bingeing behaviors.

Rat researchers know their bingeing and drugging.  A correlation between liking sweets and drugs of abuse (including alcohol, cocaine, and amphetamines) is known in humans, and in rats, repeated exposure to sucrose seems to enhance behavioral susceptibility to cocaine later on.  Sucrose is, in this paradigm, a "gateway drug."  Let's not forget that in sugar-bingeing rats, taking away the sugar leads to opiate-like withdrawal syndromes and worsens the withdrawal from morphine.  So let's say you are a binge-eater withdrawing from a sugar-fest -- are you more likely then to have a bottle or two of wine, some meth, or cocaine?  Could be.  Even though these different drugs of abuse affect different reward neurotransmitters, they all end at one common pathway, which makes sorting out some of the specifics rather difficult.

Here is a money excerpt from the paper:

Offering further support for the connection between the intake of sugar and fat and the intake of drugs of abuse are several studies investigating the neuroanatomical and neurochemical changes that accompany sucrose and fat consumption. Not surprisingly, these sugar and fat consumption-induced changes occur in the mesocorticolimbic dopamine system, a major component of the brain’s reward pathway, and many of the changes mimic those that occur after exposure to drugs of abuse, including turnover and release of DA, D2 receptor binding and expression, and dopamine transporter binding and expression. In addition, differential responsiveness in rats bingeing on fat has been reported when a D2 receptor antagonist is administered peripherally, or directly into the prefrontal cortex.
In short, eating fat and sugar seems to engage our reward systems in the same way that drugs of abuse do.  This is not terribly unsurprising - we have a reward system for our survival.  Protein is easy to find in the paleolithic world (ask any bug or lean rabbit) - but what about our fuels of sweet and fat?  We need it, we love it, and our big brains encourage us to find it and consume it, and drives us to find it and consume it again.  My suspicion (not first thought of by me in any respect!) is that, like cocaine, Snackwells, Oreos, Big Gulps, potato chips, peanut M&Ms and deep-fried twinkies stimulate our reward centers in ways our brains were never designed for, like a magnitude 9 earthquake taking out at magnitude 7-rated nuclear reactor.  To parse matters even further - the actual substances may be less important than the manner in which they are consumed.  A sugar binge (with all the sweaty anticipation, consumption, aching stomach and crashing blood sugar later on) is a far more worrisome issue than eating the same amount of sugar over the course of a day, at least in rats.  Here we separate those who are (for whatever reason - environment, genes, etc.) vulnerable to addiction and those who are not.  

So what happened to these rats with the cocaine and the crisco, anyway?  The methods are a bit boring, but in short, we have some rats on standard rat chow, and then some rats on standard rat show plus access to fully hydrogenated Crisco (not sure where you can get your paws on that nowadays!  J.L. Smuckers must have a special research repository in the basement.  Actually, wasn't it the partially hydrogenated Crisco that was the bad stuff?  Poisons are so confusing...)  All the rats were then transported to another lab 90 miles away (in Hershey, PA, which is a lovely community of nostalgia and chocolate), where there was no Crisco, but there was some high quality blow (actually it was IV cocaine, and the rats could control the administration by licking a certain spout, leading to an infusion of the drug.  Interestingly enough, a study was once done on humans comparing IV cocaine, IV amphetamines, and IV caffeine, and the humans could not tell the difference.)

You will not be surprised to learn that the indulgent, gluttonous crisco-bingeing rats were mostly the same ones who had a bit too much affection for the cocaine.  The other, abstaining rats were rather like Meg Ryan in "When Harry Met Sally"  "I don't like to eat between meals."  So superior, so sure that all you have to do is exercise some self control, as they do, and you could wear size 2 jeans, no problem.

I know, it is a big leap from a few crisco-loving, coke-addled rats to 60% of the population being overweight or obese.  But certainly there is something there.  And for the love of all that is precious and good, DO NOT EAT HYDROGENATED CRISCO (even though it is much better than the partially hydrogenated stuff**).  


** In the US, anything less than 0.5mg trans fat per serving can be listed as "0g trans fat."  Does anyone know the fully hydrogenating process for New Crisco and how good it is at getting all the double bonds saturated?  Or are quite a few missed and you end up with a small dollop of trans fat each time, still?


  1. As a poster child for BED, I found this presentation* from the 2009 food addiction summit to be very interesting ... especially the relationship between binge-eating and deprivation.

    Yes, not all obese folks are binge-eaters, but it'd be interesting to check the correlation between obesity, binge-eating and deprivation diets (I did my first liquid protein diet in my teens).


  2. Does anyone know what they do to these Linoleic acid cooking oils nowadays to make them "cooking stable" since hydrogenation has gone out of favor?

    If the crisco really is "fully hydrogenated," I'd argue it's actually perfectly safe. Fully hydrogenating linoleic acid will give you stearic acid and no trans fats, which is perfectly safe and healthy. Seriously.

  3. Rats will binge on plain crisco? Blarg! Didn't Ratatouille teach them anything? Oh right, I suppose they haven't seen it. Well there's their culinary Messiah, if only we could install movie screens in the sewers.

    So it looks like the modern environment of hyperstimulation doesn't discriminate between types of stimulation, which makes sense. That's interesting, and I think that my personal experience supports it. Except this is with music. I find that when I listen to ridiculously melodic and well-produced modern metal and techno I am more impulsive and stimulation-seeking, and I become less so when I withdraw those genres and listen to more jazz and classical where the appeal is in the nuance and sophistication.

    It's the kind of distinction Stephan has been trying to make between gourmet French cuisine and oreos, the oreos are more stimulating, but not necessarily more enjoyable on a visceral level. The crux is that I'm not looking to add cheese to everything or to use store-bought steak spice, I don't seem to seek those as much. This is probably a product of less overall stimulation.

    I'm totally with you on never eating crisco, for many reasons. But do you think that crisco might also cause brain damage that contributes the dysregulation of the reward pathways? I know that's too speculative for you to blog properly on yet, but after reading this Paul and I started to believe that there is at least a modest effect of inflammation on binging that has to do with poor leptin signaling.

    It's all making sense now. Now, years later, I can totally see how the combination of drugs, junk food, hyper-melodic music, and lack of sleep messed with my head and made me depressed and anxious. Cheers for all of the great posts and insights. NO to Crisco, cocaine and other junk. I'm not going to give up my favorite music, but just not listen to it constantly. Moderation seems to work just as well as abstinence

  4. Hi Emily,

    I'm surprised I haven't seen more talk of your previous posts with all of the recent writings about food reward and such. I notice my behaviors fall closely in line with the rats: I usually eat 2 or 3 meals per day and definitely "binge" during that time, but when the meals are high fat, I don't crave more fat soon after or get "cranky;" I just experience normal hunger eventually. With high carb (bananas or sweet potatoes), I soon experience a strong desire for more, despite a full stomach. There's a huge difference between feeling full and satiated.

  5. EH - yeah, remembered that after the fact and just corrected myself, but I really need to look that engineering process up.

  6. Somehow sweet things are much sweeter in America then in other countries and many supposedly unsweetened things contain too much sugar. In the light of the research you just presented it could make same difference.
    The research may also give a hint why some mind-altering substances traditional cultures use for centuries - like coca leaves, cannabis, tobacco cause so many problems for population in civilized countries. People in modern countries could be more susceptible to addictions than in traditional societies due to more refine carbohydrates in their diet.

  7. John - I have no problems with things like bananas for breakfast. As long as my diet for the most part is paleo with plenty of healthy fat it seems to be somewhat bulletproof. Other "safe starches" also don't seem to cause cravings or issues for me. I know of other people who have major issues with carbs. I can't explain the difference at this point.

  8. So if fat/sugar bingers are most likely to get addicted to cocaine, and 33% of obese people are bingers, then that third of the obesity epidemic should pretty much cancel itself out via drug induced starvation... if only we would just stop the war on drugs that is.

    Nice article Emily! Even though this kind of research is basically stupid because vegetable oil studies don't tell you much about how the body really works, the correlation between food addiction and drug addiction is interesting.

  9. John and Emily, bananas and sweet potatoes would cause me terrible cravings with or without fats or proteins or nothing. However, certain other carbs cause no cravings for me at all. I wonder if the severe food cravings that some of us experience is a result of a difference in our gut ecology. I don't want to say it's a dysbiosis (bad connotation) because I'm probably just as healthy as anyone who can digest sweet potatoes and bananas, but my colony down there just isn't the same.

    I have found after years of experimentation that it isn't about carbs. It's something else. We blame carbs because we are taught to blame carbs.

  10. How do you reconcile this with the observation that obesity features central stimulant insensitivity? Cocaine self administration in rats (and probably humans) is a function of central catecholamine sensitivity, which in turn is inversely related to food intake. It seems unlikely that a condition which promotes obesity, would also promote cocaine seeking behavior; this is not consistent with what we know already.

    If you want to see a rat go crazy for coke, starve that rat. Dopamine receptors sprout like mad and it is uber sensitive to stimulants. The starving wired rat just slams the coke lever like forever. Fat rats are like "meh, me sleepy".

    The ironic thing is, it might have been the restriction SSTT days which were making that rat coke crazy. The relative restriction probably modulated it dopaminergic system to be like DOPAAAMIIINE , much in the same ways absolute restriction does. In other words, the rats were coke crazy not because of fat binging, but because of fat RESTRICTION. The binging, itself, was just another sign of restriction (thus amped up d2 receptor and low serotonin).

    This would be consistent with all other research. The idea that binging on fat could somehow make a person more responsive to cocaine is not consistent with prior research, which suggests that food intake and the development of obesity (high glucose/insulin) rapidly downregulates d2, which terminates response to cocaine (thus seeking behavior reduced)

    Once in this state, you do not self administer cocaine anymore - why would you? Would you take a drug that your brain cannot feel? This is the whole deal with maintenance drugs like naltrexone and antabuse. You plug up endorphin receptors and suddenly you don't really want to score some heroin anymore, no high.

    I think if bulimics have other impulse control disorders, and an excessive response to simulants, it's probably because bulimia/binge disorders also features self starvation, just like the MWF rats (forced bingers) and bulimics do feature many physical commonalities to anoretics, like hypoleptinemia and weight loss and a general physiology geared around food restriction. If you eat nothing for 1 day and then binge and purge on the second, your brain is still wired like a starving person - it still shows signs of food restriction like low serotonin, and doapmine sensitivity.

    We are viewing this as if the binging caused these problems, when it is far more likely the binging is just another symptom of restriction, much like cocaine craziness.

    This is also the case in human binge eaters - I have never met a binger who also didn't starve themselves. I think the main difference between people who respond to chronic food restriction with binging, and people who respond with an anoretic-like response (these are the only two possible responses), is central serotoninergic activity plus basal dopamine. If serotonin is very low, the person will exhibit a binging profile; if serotonin remains relatively high even while starving, the person can easily inhibit behavior and will not ever binge. Higher dopamine levels (secondary to low serotonin) will also promote binging in a starved state. SSRIs help bingers because they correct this dopamine/serotonin imbalance.

    This is consistent with research that people who develop severe restrictive ED (anorexia nervosa) have abnormally high serotonin, and personality traits of people who are able to compulsively starve are similar - perfectionistic, harm avoidant, low novelty seeking, low hedonic.... this is the blueprint for a brain that is uber serotonin and low dopamine, which helps one starve themselves to death if they are so inclined.

    I find it extremely easy to inhibit behavior, I once weighed 100 pounds and hardly ate and ins pite of feeling extreme hunger I had no risk what so ever of acting in response. My personality is just like that.

  11. Peggy - yes, what this study shows us is that something in the reward pathway is out of whack with binge eaters - particularly rats who will binge on sugar or fat. We already knew something was out of whack with binge eaters, however, and clinical experience should lead one to suspect the reward pathways as the syndromes of binge-eating, bulimia, and substance abuse overlap, and a binge-eater just sounds an awful lot like an addicted person when talking about the binge, clinically. We knew sugar did it, now we know hydrogenated crisco does it too. If it is strict stearic acid, that would be very interesting. If it has trans fat, it may not be as interesting.

    I don't know any humans who binge on crisco, however. I mean, the researchers did not use butter flavored or salted crisco. They used straight-up crisco.

  12. Woo - binge-eating rats and mini-pigs will binge eat, spontaneously fast, and then binge again, even if the food is available consistently. If the binge-promoting food is taken away (in rats) for two weeks, when it is reintroduced, the binge will be bigger than ever before. Binge-eating typically does not cause obesity in rats - the fasting makes up for it - until you combine sugar and fat. However, a vegetable oil binge alone (I believe) didn't cause weight gain but did seem to change body habitus of the bingeing rats to increase fat%.

  13. What do you think about the idea of all the extra sugar we have added to baby food the last few decades playing some sort of role in screwing-up reward pathways? It seems like kids are constantly reinforced to like sweetness.

  14. >In the US, anything less than 0.5mg trans fat per serving can be listed as "0g trans fat."

    I am afraid it is everywhere.

    They should change the way they teach science in schools then if 0.5 equals 0 and not 1 per approximation.

    This is cheating and I hate it, they use it to put a big label "0% trans fats" and when you read the ingredients it reads "hydrogenated oil". But if you tell someone you read labels they laugh at you or tell you have too much free time.

  15. @DrDeans
    That is not what seems to have been observed in this study. I don't know about binge eating rats in other studies (were they genetically bred to be bingers?) but in this study using standard lab rats, the only rats that binged were the ones who were restricted.

    It seems then that the fluxing levels of nutrients may have been the trigger to develop a brain wired to binge, not some magical intrinsic rewarding properties of fat. It also stands to reason this restriction induced brain wiring also predisposed to disinhibition with drugs (probably mediated by dopa responsiveness and low serotonin, as in the case of humans with problems featuring impulsivity/risk taking/compulsive obsessive addictive behavior)

    And, regarding bulimia and substance/impulse problems... bulimics phenotypically are very similar to anoretics, in the sense that they are at a nutritional deprivation state, engage in long periods of food restriction, have hypoleptinemia relative to their body fat levels, often have amenorrhea from food restriction/nutrition deprivation; it stands to reason that their brain is also wired around starvation (low serotonin, high dopamine responsiveness). This is a recipe for impulse control disorders of all kinds, serotonin inhibits behavior / emotions and dopamine leads to disinhibition/risk taking/thrills and so on, but I'm sure you are well aware of that.

    The reason anoretics are even possible is because it has been shown people with purely restrictive AN have an abnormally hyperactive serotonin system - dopamine is suppressed in a fed state, and in a fasted state, serotonin does not drop as much. Many anoretics feel "better" while starving for this reason.
    This is why females frequently develop it and males rarely do - the female brain is serotonin dominant and dopamine deficient. Any normal person would find themselves face down in a box of doughnuts before they could even think of doing it. An anoretic is capable of feeling pain, extreme death-like hunger, and not having normal drive/motivation to disinhibit and impulsively respond. As anorexia becomes advanced they lose normal feelings of hunger all together and the GI system shuts down.

    Anyway there is so much nonsense about this circularly defined "food reward" crap, it has become almost impossible to consider that over eating behavior might not have anything at all to do with this yet to be proven "food reward" thing.
    I find it hard to see this as evidence of food addiction/reward if the only rats who binged were the ones exposed to the condition of restriction.

  16. Woo- all the rats were restricted. They were all moved from the crisco lab to the cocaine lab. Not all the rats binged, and the ones who did binge on crisco later were more likely to binge on cocaine.

  17. @Woo, actually all rats in the study had unrestricted access to standard rat chow throughout the shortening-exposure portion of the study. Access to shortening followed different protocols. Here's the text from the paper:

    "Briefly, the rats had continuous access to the rodent diet described above and water throughout the study, and, in this portion of the study, were provided additional access to a jar of hydrogenated vegetable shortening (optional fat; Crisco® All-Vegetable shortening, J. M. Smucker Co., Orrville, OH) clipped to the front of the home cage under one of the following four conditions for a period of six weeks: no optional fat access (i.e., chow only; Chow; n 9), continuous access to the optional fat (Ad Lib; n 19), daily 1-h access to the optional fat (Daily; n 20), or 1-h access to the
    optional fat on Monday, Wednesday, and Friday (MWF; n 21). One-h fat access was provided 2.5 h before dark onset."

  18. Right - forgot the control rats. Should probably not post comments prior to 6am

  19. @Aaron & Dr Deans
    This is what the abstract says:

    "...45 adult male Sprague–Dawley rats were maintained on one of four dietary protocols for a period of six weeks: chow only (Chow; n = 9), continuous access to an optional source of dietary fat (Ad Lib; n = 12), 1-h access to an optional source of dietary fat daily (Daily; n = 12), or 1-h access to an optional source of dietary fat on Monday, Wednesday, and Friday (MWF; n = 12). All four groups also had unrestricted access to a nutritionally complete diet of chow and water. Fat-bingeing behaviors developed in the MWF rats, the group with the most restricted access to the optional fat. "

    It's pretty clear to me that the rats did have various levels of restriction, so it is not true to say "all were restricted", the protocol clearly restricted some rats more than others.
    Unless this abstract is worded incorrectly, that binging developed only in the MWF rats, the group with the most restricted access to optional fat.

    This in no way validates food reward, or that food can be addicting, or that excessive access to hyperpalatable/stimulating food rewires the brain, or any Guyenetesque thinking.

    It does, however, validate the often observed phenomenon that periods of food deprivation, withdrawing food unexpectedly, and having limited access to food DOES rewire the brain to promote impulse control disorders and heightened responsiveness to dopamine/low serotonin, which then symptomatically manifest as conditions such as binge eating and drug addictions. It may be an evolutionarily conserved mechanism to survive in environments where food availability is scarce, which is why constant food does not trigger it, but DEPRIVATION after food does trigger it.

    I am aware all rats were able to eat enough "regular" food whenever they wanted, but perhaps from a brain perspective, it doesn't much matter - it's the exposure to food and then the restriction of it, that messes your brain up.
    Being sensitized to certain levels of nutrition and then being forced to go without for a measure of time, basically.

    Sort of like, if you are exposed to a person and develop a close relationship, you are sensitized to that person and feel love, affection. If the person/thing is withdrawn (e.g. death, breakup), you go through sadness. If you had never been exposed to the person/thing, you never would have experienced this upon their absence as you had not been priorly sensitized.

    The reason this does not support FR, or some intrinsic addictive quality of fat/food, is because if we were to follow that idea through logically, the rats who had the greatest access to fat, would be the rats with the worst binging/coke behaviors. This is not the case. These rats fared better. This suggests food (or "food reward") itself did not/could not cause the brain changes required, it took the additional element of more extreme levels of withdrawal (MWF schedule).


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