One Pill Makes You Larger

Patient: “Are these time-release pills?”
Doctor: “Yes. They start to work as soon as your check clears.”

Jekyll and Hyde

Okay, so I have occasional mood swings…

As if we didn’t have enough crazy things to drive us around the bend, new research indicates that our happy pills are making us chubby. That’s right, the drugs that doctors give us to feel gladder are actually making us fatter. They’re converting our Oedipal issues into adipose tissues.

Antidepressants, antipsychotics and mood stabilizers (beware the mood that has fled the stable) are all implicated in this perverse reverse diet. In one study, ninety percent of the people who took Zyprexa, just to name one of the drugs, gained weight. A third of them managed to gain over twenty pounds, and half of that group topped up with an extra forty pounds. And that was just the first year. The long-term prospects are grim.

This particular drug is used to treat bipolar disease, which is a serious syndrome, but some of the other side effects include (this is straight from the manufacturer’s brochure): impaired judgment, discolored teeth and seizures. If you’re taking this drug, you should talk to your doctor about switching to Cheetos, which have similar contraindications, but may be better for your mood, if not your weight.

depression

Breaking out of depression without busting the scales

A large class of antidepressant drugs affect serotonin, a brain chemical that elevates your mood. They’re called selective serotonin reuptake inhibitors, or SSRIs, and they basically recycle serotonin to keep it in circulation, presumably ginning up your spirit. They are quite popular, and you might know them by their trade names: Prozac, Paxil, Zoloft, Celexa and many, many others.

Down the hatch

However, as important as serotonin is in the brain, it is even more important in your gut, where 90% of your body’s serotonin is located. I’ve been accused of thinking with my stomach and having gut feelings and it turns out, it’s all true. Your gut is a hotbed of neural activity and psychotropic drugs are everywhere. How cool is that? This is primo cocktail chatter, at least at a microbiology convention. It might even be a (dodgy) excuse for bad behavior: “My microbiome made me do it!”

When you pop an antidepressant, it splits it’s payload between your gut and your head, in that order. And the dose to your gut can be deadly to certain beneficial bacteria. In other words, some of these psychoactive drugs are also acting as antibiotics. That’s an underappreciated side-effect.

Psychiatrist and patientOn the other hand, SSRIs can encourage other bacteria that may help you pack on the pounds. In one study, a strong correlation was found between body mass index (BMI) and antidepressants. But the more intriguing finding was a connection to methane on the breath. Methane is a byproduct of certain kinds of bacteria associated with obesity and the tantalizing thought is that antidepressants may affect gut bacteria that can then alter your appetite and your ability to digest food.

We’ve actually known for a long time that the stomach affects the brain and vice-versa. In 1822, a fellow named Alexis St. Martin was shot in the stomach and was treated by Dr. William Beaumont, who didn’t expect his patient to live. Against the odds, St. Martin survived, but his body formed a fistula, or a hole, from his stomach to his side. It was gross and had to be bandaged up to keep stomach acids from squirting out, but Dr. Beaumont was delighted. It gave him an unprecedented window on digestion.

Seizing the opportunity, Dr. Beaumont took St. Martin on as a servant and semi-willing guinea pig. The doctor extracted  stomach juices through the fistula and had them analyzed. He also tied string around different foods, dipping them into poor St. Martin’s stomach and regularly retracting them to monitor the digestion process. St. Martin was not fond of these experiments, but it led to the discovery that heavy emotions can affect the amount and acidity of stomach juices. Dr. Beaumont realized that the brain could directly affect the chemistry of the stomach.

Evidence is accumulating that the reverse path, from the gut to the brain, is also viable. At least some of the intermediaries in this brain/gut axis seem to be bacteria. They are ambassadors mediating between the wishes of the host and the desires of the huge population of microbes in your gut. That two-way conversation can be sweet or horribly dramatic, running the gamut from bliss to high anxiety. The nasty end of that microbial scale may lead to illness, obesity and even death.

It’s easy to underestimate the extent of the brain/gut axis. Seemingly unrelated symptoms turn out to be strangely correlated. For instance, gut bacteria may play a role in Autism Spectrum Disorder (ASD). Granted, the best evidence comes from a mouse model of autism, but you can’t do these experiments on people yet. The ASD mouse, as well as having autistic-like behavior, also has a leaky gut, another hallmark of autism. When they dosed their ASD mice with some bacteria called B. fragilis, their entire gut ecology changed: they had a more natural mix of bacteria, with less Clostridia — and their leaky guts healed. At the same time, some (but not all) of their “autistic” behavior improved. Rebooting their bacteria seemed to lower their levels of anxiety and increased their desire to explore. The new gut bacteria changed the way their minds worked.

A pill for everyone

Two-thirds of autistic children are taking some kind of psychotropic medication, including antidepressants, but they aren’t the only ones. Antidepressants are prescribed for all kinds of mental issues, many of which are justifiable reactions to our modern, hectic world. These are people who are sad, anxious or just plain stressed out by life — some 50 million Americans. Talk about a depressing statistic! That’s one in six. Look around at five of your friends. If none of them is mentally distressed, then you’re it.

How is it that the richest country in the world has become so psychically impoverished? In the past, I might have had suspicions about a vast conspiracy between doctors and giant pharmaceutical companies to get us all on expensive medications. Fortunately, my doctor prescribed some very soothing pills that have completely purged me of such paranoid ramblings. I feel much better about it all now.

The best pill of all?

To add insult to injury, recent studies have shown that many of these wonder drugs are not much better than a placebo, which is a wonder drug of its own. Placebos are just cheap sugar pills, but that doesn’t mean they don’t work. Far from it. My Dad, who participated in more drug trials than was prudent, once told me he was addicted to placebos. He was joking (I think), but one study after another has shown that placebos really can reduce pain for people, and the more they cost, the greater the effect. In fact, red placebos work better than white placebos, probably because they seem more serious.

Doctors are now trying to get obesity classified as a mental illness. And when they do, of course, we’ll need some more drugs for that. Let’s hope they’re not too fattening.

Might we be heading down the wrong path? Instead of prescribing pills that screw up our digestion and make us fat (but not always jolly), maybe we should be getting happy by eating foods that encourage feel-good bacteria in the first place? Is there such a thing? Perhaps! New research is showing that certain kinds of gut-bacteria are associated with mood, and these fun bugs are termed psychobiotic.

That’s right, dear reader, this is a new paradigm (with a very catchy name) about the control that our bacterial overlords have over our own thoughts, so prepare for some overwrought comparisons to zombies and such. Nevertheless, evidence is piling up that there is a connection between our bacteria and our brain, and that we are swimming upstream with our current batch of psychrotrophic drugs. Instead of killing good bacteria with antidepressants, perhaps we should just be boosting our happy bacteria and skip the middleman.

Good mood food

Happy Paella

Can food make you happy? Is that really a question?

We still don’t know how to really change our gut ecology without major intervention, but there are certain “mood foods” that might help. Yogurt has been shown to make people happier, and it might work as well as a placebo or even an antidepressant.

Fiber feeds bacteria that produce butyrate, a short-chain fatty acid that helps to heal and maintain the integrity of your gut. It can even reduce the chances of getting colon cancer. Healing your gut and establishing a good ecology sends a message to your brain to be less anxious. So eat your beans and artichokes and lighten up a bit.

Bam!

A friend of mine, who has done much research on the subject, insists that the ginger they serve with sushi is better than most drugs, legal or not. I understand the feeling. Personally, I find it impossible to think bad thoughts when I’m eating spicy Jamaican food, even when they forget to add the ganja. And have you ever wondered how a miserably poor country like India manages to produce so many well-adjusted people, even when they’re employed in godforsaken call centers? Could it be the curry?

You might think this is a simplistic solution, and you would be correct. But what’s wrong with simple? Does it make better sense to take pills for depression that make us fat which then depresses us even more? Maybe simple isn’t so wacky after all; studies show that spices can be psychoactive, so why not kick things up a bit?

Okay, some of us have honestly nasty problems, and antidepressants help a lot of people get through some rough patches. And there are many researchers working on solving the weight-gain problem with some success. So listen to your doctor. But if I were borderline, I think I’d tell my doctor that I’m going to skip the pills and instead spice up my life with some good mood food.

Anxiety melts in spicy Tom Yum soup. Depression dissipates with yogurt. Sadness cannot thrive in the presence of coconut curry. Call me nuts, but I’m feeling better already.


Resources

Basseri, Robert J., Benjamin Basseri, Mark Pimentel, Kelly Chong, Adrienne Youdim, Kimberly Low, Laura Hwang, Edy Soffer, Christopher Chang, and Ruchi Mathur. “Intestinal Methane Production in Obese Individuals Is Associated with a Higher Body Mass Index.” Gastroenterology & Hepatology 8, no. 1 (January 2012): 22–28.

Munoz-Bellido, J. L, S Munoz-Criado, and J. A Garcia-Rodriguez. “Antimicrobial Activity of Psychotropic Drugs: Selective Serotonin Reuptake Inhibitors.” International Journal of Antimicrobial Agents 14, no. 3 (April 2000): 177–180. doi:10.1016/S0924-8579(99)00154-5.

De Vadder, Filipe, Petia Kovatcheva-Datchary, Daisy Goncalves, Jennifer Vinera, Carine Zitoun, Adeline Duchampt, Fredrik Bäckhed, and Gilles Mithieux. “Microbiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits.” Cell 156, no. 1–2 (January 16, 2014): 84–96. doi:10.1016/j.cell.2013.12.016.

Dinan, Timothy G, Catherine Stanton, and John F Cryan. “Psychobiotics: A Novel Class of Psychotropic.” Biological Psychiatry 74, no. 10 (November 15, 2013): 720–726. doi:10.1016/j.biopsych.2013.05.001.

Hsiao, Elaine Y., Sara W. McBride, Sophia Hsien, Gil Sharon, Embriette R. Hyde, Tyler McCue, Julian A. Codelli, et al. “Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders.” Cell 155, no. 7 (December 19, 2013): 1451–1463. doi:10.1016/j.cell.2013.11.024.

Wattanathorn, Jintanaporn, Pennapa Chonpathompikunlert, Supaporn Muchimapura, Aroonsri Priprem, and Orathai Tankamnerdthai. “Piperine, the Potential Functional Food for Mood and Cognitive Disorders.” Food and Chemical Toxicology 46, no. 9 (September 2008): 3106–3110. doi:10.1016/j.fct.2008.06.014.

Gomez-Pinilla, Fernando, and Trang T J Nguyen. “Natural Mood Foods: The Actions of Polyphenols against Psychiatric and Cognitive Disorders.” Nutritional Neuroscience 15, no. 3 (May 2012): 127–133. doi:10.1179/1476830511Y.0000000035.

Scharlau, Daniel, Anke Borowicki, Nina Habermann, Thomas Hofmann, Stefanie Klenow, Claudia Miene, Umang Munjal, Katrin Stein, and Michael Glei. “Mechanisms of Primary Cancer Prevention by Butyrate and Other Products Formed during Gut Flora-Mediated Fermentation of Dietary Fibre.” Mutation Research/Reviews in Mutation Research 682, no. 1 (July 2009): 39–53. doi:10.1016/j.mrrev.2009.04.001.

Tillisch, Kirsten, Jennifer Labus, Lisa Kilpatrick, Zhiguo Jiang, Jean Stains, Bahar Ebrat, Denis Guyonnet, et al. “Consumption of Fermented Milk Product With Probiotic Modulates Brain Activity.” Gastroenterology 144, no. 7 (June 2013): 1394–1401.e4. doi:10.1053/j.gastro.2013.02.043.

Kirsch, Irving, Thomas J. Moore, Alan Scoboria, and Sarah S. Nicholls. “The Emperor’s New Drugs: An Analysis of Antidepressant Medication Data Submitted to the U.S. Food and Drug Administration.” Prevention & Treatment 5, no. 1 (2002). doi:10.1037/1522-3736.5.1.523a.

Jacobs, Keith W., and Frances M. Nordan. “CLASSIFICATION OF PLACEBO DRUGS: EFFECT OF COLOR.” Perceptual and Motor Skills 49, no. 2 (October 1979): 367–372. doi:10.2466/pms.1979.49.2.367.

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