The one way smoking makes you healthier

Would you rather have lung cancer or a neurodegenerative disease?

I know, I know, it sounds like a clickbait title, so we’ll cut to the chase:

It’s Parkinson’s disease. Specifically, smoking drastically reduces your risk of getting Parkinson’s. As far as we can tell, it’s causal. Keep in mind, this is only prevention: if you’ve already got PD, a pack of Parliaments won’t save you.

Still, much to the chagrin of public health officials worldwide, study after baffling study has shown that nonsmokers are almost twice as likely as smokers to get Parkinson’s to begin with. It behaves exactly like a preventative medicine, too: the more you smoke, the lower your risk of PD. If you stop smoking, your odds begin slowly increasing again, until they’ve returned to normal. A few years back, I met a clinician who shared that—in his experience—if a patient presenting with tremor is a smoker, it’s not even worth considering Parkinson’s as a diagnosis until everything else has been ruled out.

If you really twist yourself into knots, you can maybe convince yourself that the study of 30,000 doctors I linked above¹ is wrong in its assessment of causality: maybe smoking selectively kills off all but the sturdiest people, so those smokers who remain alive into the stage of life where Parkinson’s becomes a serious risk are just disproportionately robust and healthy.

But I don’t think that’s what’s going on here, partly because cigarettes aren’t the only thing that reduce your risk of Parkinson’s.

Coffee does, too.

“What, I’m a neurologist, not an oncologist!” (Image credit: Dall-E 2, which still needs some work on the whole “eyes” thing.)

Here again, it’s a dose-dependent effect: the more coffee you drink, the less likely you are to get Parkinson’s.

That might depend on how you take your coffee, though—because milk increases your risk in a dose-dependent manner.²

If you’re wondering “what the hell is going on here?”, it might help to understand a little about the pathology of Parkinson’s.

The most characteristic symptom of the disease is tremor—a weird, intermittent, uncontrollable shaking. It’s not at all like a shiver; tremors are more like hiccups, in that they’re the result of one part of your nervous system losing touch with another.

With hiccups, that’s your midbrain losing track of what’s going on with the sensory nerves down by your diaphragm, panicking a little, and then re-establishing contact with a spasm of activity. In Parkinson’s, the parts of your nervous system that have lost touch are right next to each other in your brain, components of a dopamine-rich neural circuit that controls movement.

In Parkinson’s, those dopamine-rich neurons die off, and the tremors emerge when signals in that circuit start to get shoddy—but this only happens once about 90% of those neurons are already dead and gone. This is a relatively slow thing, meaning that whatever degenerative process results in Parkinson’s disease is likely at work for years before the shimmies and the shakes show up.

So, back to the point: how do coffee and cigarettes prevent Parkinson’s? As you might have guessed, there’s a microbiome angle.

See, for a lot of people, the first sign of Parkinson’s isn’t tremors—it’s constipation. World-ending, anus-rending constipation. It can hit twenty years before the tremors, around the time that neurodegeneration starts, rather than when it reaches a full gallop. While this suggests that constipation might be a useful biomarker to enable early interventions, it’s rarely recognized as the first symptom of PD until after the fact, for the simple reason that constipation can be caused by so many other, less threatening things. It’s also tough because there’s no definitive test for Parkinson’s, and the only approved treatments just help to manage symptoms rather than doing anything to alter the course of the disease—so earlier diagnosis would mostly serve to remind you of your impending fate every time you strain to drop a deuce.

This also makes it really difficult to suss out the direction of causality. Is constipation simply an early consequence of neurodegeneration, or is it somehow involved in the disease process?

The Three Cs

Years ago, I explained these findings to a French friend of mine, and she informed me that her people have a saying about the “3 C’s” that go together like nothing else—café, clope (cigarette), et caca. Cigarettes and coffee are great laxatives.

It’s enough of a thing that they have it on novelty mugs.

Now, to be clear, I’m not saying that coffee and cigarettes’ protective effect is necessarily because they keep the poops moving along, although I do think there’s value in this kind of magical thinking. Does anything with a strong laxative effect lower PD risk? That’s a surprisingly tricky question to answer: observational studies of things like laxative use vs. PD risk are pretty much useless, since laxative users are already constipated by definition.

In theory, you could answer it with a prospective interventional study: Just get some otherwise-healthy middle-aged people, have them take a laxative once a day for, oh say, twenty years? Then just count how many of them get Parkinson’s and compare it to an age-matched control cohort!

Good luck getting people to sign up for that one.

The precise reason why drinking coffee and smoking cut your risk of PD will have to remain a mystery for a while longer, but it's still a tantalizing clue. Part of the reason these bizarre findings have a special place in my heart is that I first learned about them right as microbiome science was beginning to pick up steam as a field, and to me it was the first major hint that there’s something gastrointestinal to the etiology of the disease.³

Of course, other people took notice back then, too—which is why they eventually just went and did a study of fecal transplant for Parkinson’s, with relatively spectacular results.

Each of these lines represents a Parkinson’s patient who received an FMT; these charts are all different scales for measuring the various symptom domains of Parkinson’s.

That study didn’t have a proper placebo control group, but—while placebo can be a hell of a drug—it usually takes a lot more than “hope” to make a person’s Parkinson’s spontaneously regress for a few months. They also point out in the article that, while ten of their patients saw these improvements, five of the fifteen participants didn’t. The interesting thing is that all ten patients who really improved got their fecal transplant via the colorectal route (think ‘‘topsy turvy enema’’), while the five who didn’t see improvement had opted for the "nasointestinal” route, i.e. a thin tube that’s run up the nose, down the esophagus, and through the stomach to the small intestines. The authors argue that these patients serve as a kind of control group, and that this hints that the large intestine/colon is where Parkinson’s disease really begins. I want to see bigger and better studies before I draw any conclusions about mechanisms of action, but slowly and surely that data is starting to emerge.

There are a lot of natural follow-on questions from here. Does the cigarette effect also apply to vaping? Since Parkinson’s can lurk in the “prodromal” phase for decades, it’ll likely be another few years until e-cigs have been around long enough for us to properly study their impact on risk.

In the meantime, it’s hard to go wrong with a black coffee.

🖖🏼💩

1. Yes, it was a study specifically of doctors who smoked. Make of that what you will, but they had to do some accounting for the fact that rates of smoking among doctors dropped precipitously over the fifty years of the study’s period.

2. This effect may be unique to America, as a case-control study in Japan found no effect. Bonus points to any reader who’s willing to do the math and figure out the balance of coffee vs. milk that evens out your risk ratio to 1.

3. The other reason why they have a special place in my heart is that there are few things better than a spliff and a coffee on a Saturday morning, and everyone loves a rationalization for their guilty pleasures.