Don't put down the Fritos: Salt cravings and your crack habit.

One of the interesting things about being a scientist is reading how science is interpreted in the mainstream media, and then comparing the headlines back to the science that was, you know, actually done. When I was a young, and highly naive little scientist, I would read the headlines and go "oh, wow, they found that brain structure and hormone use are correlated in women and makes them behave differently. They must have done all of that stuff in the study".

HAHAHAHAHAHAHAAHA. No, no they didn't. At first I was often surprised to find that the media would put all the hypotheses and suggestions in the discussion of the article in as fact, and it turns out that the people doing the study wouldn't have done ANY of those bits AT ALL.

Now, I am not as young (sniff), and I am slightly less naive. So when I saw headlines like "Salt Appetite Is Linked to Drug Addiction, Research Finds", "Cocaine Addiction Uses Same Brain Paths as Salt Cravings", "Appetite for salt linked to drug addiction", I know that you can't ASSUME that they tested the actual drug addiction propensities implies in the studies.

So when you see headlines like this...don't put down the Fritos. Put down the Fritos because those things are gross and probably terrible for you, sure (have you SEEN the fat content on those things?!), but not because they make you a crack junkie.

Liedtke, et al. "Relation of addiction genes to hypothalamic gene changes subserving genesis and gratiļ¬cation of a classic instinct, sodium appetite" PNAS, 2011.

This does not mean this is a bad paper. On the contrary, it's a fine paper. But it does mean, yet again, that you shouldn't believe everything you read.

For starters: "salt appetite" doesn't just mean that you prefer butter style popcorn to kettle corn.


(mmmm, salt. Source)

(And finally a small rant. ", research finds"? ", research finds"?!?! Who the heck thinks that's good sentence structure or in anyway improves the headline?!!? I see this all the time and it always makes me cringe a little. Argh)

When we talk about salt craving here, we're not just talking about the fact that I really like popcorn (and I really, really do. None of your crappy buy it in a bag pre-popped stuff. No, I make it on the stove. HARDCORE). We are talking about a biological craving for salt that is present in most herbivores and omnivores (not so much in carnivores, who get a lot more salt from the diet).

If you've grown up in the country, or around people who do hunting or raise farm animals, you'll know that one of the most tempting items you can set up in a forest or farm is...a salt lick. A big chunk of salt. A deer will be on that in minutes, and slurping away. Salt appetite is a very strong craving that can be almost similar to thirst in intensity. It's generated, obviously, by sodium depletion (you sweat it out, you pee it out, lots of ways to get rid of salt), but is also generated by stress, and apparently also by reproduction (though the paper did not say whether that meant HAVING babies or the act of MAKING babies).

And it's something which animals are capable of gratifying very quickly. Some animals can drink LITERS of salt solution in minutes under the right conditions. Salt is an incredibly important physiological substance, so it makes sense that a craving for it might be pretty useful.

Where does this craving originate? We can't say for certain, but the authors of this study were looking mostly at the hypothalamus, an area of the brain that influences a lot of instinctive behaviors and also that is very sensitive to adrenocorticotropic hormone (ACTH), a stress hormone that can stimulate a salt appetite. And this is in fact what the authors did. They took ACTH and infused it into the hypothalamus, creating a salt craving in mice. They allowed half the mice to satisfy the salt craving by drinking salt water. Then they took the hypothalamus, along with some other areas of the brain, ground them up, and looked to see what genes showed changed expression.

This creates some pretty little arrays.

What you can see here is a gene array with two methods of inducing a salt craving. The first is furosamide, a drug that is a potent diuretic (in the immortal words of my pharm professor "it could make a brick pee"). Giving a dose of furosamide will cause the animal to pee a LOT, causing massive thirst, and if you give water enough, will result in a salt-specific appetite. The second method is the ACTH method, which creates a salt craving directly. You can see that there's a big difference in gene array between the two conditions and no salt craving, and another difference when the researchers allowed the salt craving to be satisfied. The gene names are along the side. There are a whole bunch involved (some of which only made it into the supplemental data), but some of the ones I'm seeing here look like a decrease in dopamine D1 receptors (DRD1), dopamine D2 receptors (DRD2), the dopamine regulated proteins DARPP-32 (PPP1R1B in the array), etc, etc. While the degree to which the changes occur differs between the furosamide and the ACTH, the changes for craving and satisfied craving are in the same direction.

What the authors got interested in here was that many of the genes regulated by salt craving are also genes that are known to be regulated in things like drug addiction. So they then set out to examine how changes in receptors related to drug addiction could change salt cravings. They gave salt craving mice antagonists for three receptors, the dopamine D1 and D2 receptors, and the glutamate receptor 5 (which I've been hearing a lot about lately, might be coming in to fashion amongst the addiction people. Yes, we do have receptor fashions in science). Sadly, they kicked the glutamate receptor data to the supplemental data, which I don't have access to at the moment. But the dopamine data is there to see.

You can see on the top two graphs especially how salt intake in the craving mice was changed by different doses of D1 and D2 antagonists. Both of them decreased salt intake in the mice, which backs up the idea that D1 and D2 receptors (as indicated in the gene array) play a role in salt craving. BUT, it's not as simple as all that. I want you to look at Figure C, there. Those are wildtype and D1 knockout animals. You can see on the right that the D1 knockouts didn't have an effect of D1 antagonists on salt craving (of course they don't, they don't have any D1 receptors). But they DO still have salt cravings. BIG ones. Just like the wildtype. This means that salt craving in animals is way more complicated than just dopamine, but it also means that dopamine receptors (in the hypothalamus specifically) can influence how MUCH salt the animals take in (as for salt CRAVING, I'd have to see place preference or self-administration to say for certain).

Now here's what exciting about this paper: it's that we now know that there is a gene regulatory pathway that controls sodium appetite. We did not know that it was that specific before. But it turns out it is, sodium is THAT important. And the gene regulations for this pathway overlap with some of those in addiction related pathways. This actually doesn't surprise me one bit, and supports the hypothesis that there are specific pathways present for "craving" regardless of what it's a craving FOR. Though other papers have suggested that salt craving and drug sensitization may very well go together, this paper actually did not show that, and did not study changes in drug intake with salt craving. More importantly, it did NOT show that animals with extra salt craving might be more prone to addiction (though it'd be awfully interesting if it did). It only showed that changes in receptors RELATED TO addiction pathways can ALSO impact salt intake in salt craving animals. It suggests that the two cravings might be related, and supports the hypothesis that drugs of abuse hijack natural craving and reward related pathways in the brain.

But it doesn't mean that people with major salt cravings are more likely to be coke junkies, which is the assumption you're going to come to if you skim those headlines and articles. That, that would be a different study entirely.

Finally, yes, this does mean that salt intake and salt craving produce changes in your brain. If you read me at all, you should know right now that this isn't so shocking. BREAKFAST changes your brain. BREATHING changes your brain (at least, certainly as compared to not breathing). EVERYTHING CHANGES YOUR BRAIN. Can we just keep repeating that together until headlines like "the presence of mylar balloons changes the brain!" cease to exist?! PLEASE?!

Liedtke WB, McKinley MJ, Walker LL, Zhang H, Pfenning AR, Drago J, Hochendoner SJ, Hilton DL, Lawrence AJ, & Denton DA (2011). Relation of addiction genes to hypothalamic gene changes subserving genesis and gratification of a classic instinct, sodium appetite. Proceedings of the National Academy of Sciences of the United States of America, 108 (30), 12509-14 PMID: 21746918

6 responses so far

  • FiSH says:

    Interesting paper. And I can't agree with you enough about the popular press, although I don't think it is necessarily something about the press, per se, but rather something about how non-scientists in the general population totally lack any scientific understanding (and hence understanding) whatsoever. Oh, and for the record, I still like Fritos.

  • FrauTech says:

    Oh thank goodness I can keep eating fritos.

    I only pay attention to studies that tell me that drinking lots of coffee is actually good for me. Sort of like political bias where you only pay attention to facts that only support your side. I only read studies that tell me caffeine and fritos and chocolate are actually good for me.

  • Inquisitive Mom says:

    I found your article through searching for possible connections between my child's salt craving and bad behavior. I enjoyed your writing style. I am one of those non-scientists FiSH mentioned, but don't let that fact decrease my compliment on your writing.

  • Jess says:

    Great article.
    I wish there was a magazine/website/blog that would fact check every science reporting bit in the mainstream news, and poke it full of holes (the reporting, mainly, not the science) as you've done. Especially in such a humorous way.
    This is like the Daily Show for science.
    Perhaps I should read your blog.

  • Jody says:

    I have craved salt since I was a young child. No desire for drugs. In fact I have become very sensitive to a long list of drugs that I can not take. Salt craving leading to drug sensitization make a lot more sense. But then it could be because I never had any drugs growing up as I never had any childhood diseases. That too may be because of the salt. Would be interesting to find the answer some day.

  • Beth says:

    My young daughter has a huge salt craving and severe alcohol and drug addictions run on both sides of the family; I found information about the pathways interesting. What was funny is that I saw an article called "Cocaine Addiction Uses Same Brain Paths as Salt Craving" first, and then found your page.