A weekly read on the gut, the brain, and the wiring in between. One clinical pearl, one paper, one product, one person. No hype, no selling, just the stuff I actually think about.
1. Practice
Three things to do if you take sertraline.
Sertraline is Zoloft. It is the most prescribed antidepressant in the country, and about one in eight American adults takes something in its class. I have patients on it. I have family on it. It is a good drug, and nothing below says to stop it.
The label leaves one thing out. Thiamine, vitamin B1, cannot get from your food into your blood on its own. It needs a doorway in the gut wall, a protein that carries it through. Sertraline sits in that doorway. At the doses people take, it sits there hard. The paper in the next section is where that comes from.
Low thiamine does not announce itself. It looks like this: tired for no reason, foggy, queasy in the morning, bloated, appetite gone, feet that tingle, a heart that races when you stand up. Read that list again as a person with depression on a new medication. Every item on it has two other explanations ready. The depression. The drug. A third explanation never comes up, because nobody is looking for it.
One. Do not stop the sertraline. Stopping it on your own brings its own problems, and a vitamin question is not a reason. This issue adds a question. It does not remove a drug.
Two. Count the doors. Sertraline is not the only common drug in the doorway. The same screen found metformin, the diabetes drug. Amitriptyline, the old antidepressant now used for sleep and pain. Hydroxychloroquine, for lupus and arthritis. Trimethoprim, half of the antibiotic Bactrim. If you take two of these, the door is blocked twice. Add drinking most nights, a weight-loss shot that kills appetite, or months of vomiting, and less thiamine arrives at a door that is already half shut.
Three. Ask for the level by name. "Whole-blood thiamine" is the test. It is a routine send-out from any hospital lab. Say why you want it: how long the fatigue has run, when the queasiness started, and the date you started the drug. If it comes back low, the fix is simple and it belongs to the person who prescribed the sertraline. At higher doses thiamine stops needing the door and soaks through on its own. That is a prescribing decision, and it starts with a number.
2. Publication
Vora and colleagues, American Journal of Clinical Nutrition, 2020. The screen that found the door.
This story starts with a cancer drug. In 2013 the FDA halted trials of fedratinib, a drug for a bone marrow disease, after eight patients developed Wernicke's encephalopathy. That is the brain injury of severe thiamine deficiency, the one we see in the emergency department in people who drink and do not eat. These patients were not drinking. The drug had blocked the doorway thiamine uses to enter the body, and their brains ran out.
A group at the University of California, San Francisco asked the obvious next question. If one drug can do that, which others can? They ran 1,360 compounds, most of them drugs already on the market, against the thiamine doorway in the lab. 146 of them blocked it.
Then came the step that matters. Blocking something in a dish means nothing if the drug never reaches that concentration in a person. They took each drug's largest usual dose and worked out how concentrated it would be in the gut after swallowing. Then they compared that with the amount needed to block the door. Fedratinib, the drug that started this, came out at about 600 times what was needed. Sertraline came out at about 200 times. Metformin came out at about 90. On the paper's own table, each of those drugs carries the same note: a human interaction study is recommended.
They also looked at hospital records. Patients on these drugs, in groups already at risk, had lower thiamine levels than patients who were not. The sample was small and the authors say so. Treat it as a signal.
That paper was accepted in 2019. I looked for the human study on sertraline that the table asked for. I could not find one.
A second paper picks up the thread. In 2024 a team at the European Molecular Biology Laboratory in Hamburg published the first detailed pictures of the doorway itself, with blocking drugs sitting inside it. They found seven more drugs that block it. Antidepressants are on their list of known blockers. The pictures explain how the door closes. They do not tell us how many people it has closed on.
3. Product
DailyMed. Free, no account, every drug label in the country.
Unsponsored, no affiliate relationship, no brand. DailyMed is the National Library of Medicine's public copy of the official prescribing information for every approved drug, at dailymed.nlm.nih.gov. It is the same document your pharmacist reads. Most people have never opened one.
Try this. Search Inrebic, the brand name fedratinib was finally approved under in 2019. The first thing on the label is a boxed warning. Check thiamine before starting. Check it during treatment. Give thiamine if it is low. The cancer drug that blocked the door carries the warning in the loudest type the FDA has.
Now search sertraline. Read the whole label. The word thiamine does not appear.
Same door. One drug blocked it in front of trial investigators who were counting adverse events, and the label was written that year. The other blocked it in a dish six years later, in a paper most prescribers have never seen, and the label has not changed. A label is a record of what went wrong where someone was watching. DailyMed lets you read it for yourself, and it is the fastest way to find out what your own medications were checked for.
4. Person
Kathleen Giacomini, University of California, San Francisco.
The senior author on the 2020 paper has spent her career on transporters, the proteins that carry drugs and nutrients across cell walls. For most of medicine's history these were ignored. Drugs were assumed to drift through membranes on their own. They do not. They are carried, and the carriers can be blocked or fought over.
Giacomini led the group that wrote the first widely used rules for testing new drugs against transporters, published in 2010. Drug companies now run those tests before a drug reaches you. That is why your pharmacist knows some drugs fight over the same carrier. The rules were written for drug against drug. Drug against vitamin was not in them. Her lab is the one that went back and asked.
She is a member of the National Academy of Medicine. Her lab page is at pharm.ucsf.edu/giacomini, and the 2020 paper is free to read on PubMed. She is worth following because she works on the part of pharmacology that decides whether a pill gets where it is going. When a trial blew up over a vitamin, she treated it as a question instead of an accident.
If you take sertraline and you have been tired and queasy for months, there are three stories that fit. The depression. The side effects. The door. From the outside they look identical, and the first two are already on your chart.
The third needs two things to show up. A level, which you have to ask for by name. And a record of when the tiredness started against when the prescription started, which nobody keeps for you.
That is what MeNome is for, our free app at menome.belly-md.com. It does not check your blood. It keeps the dates, a minute a day, so that when you ask for the level you can say when things changed and what changed with them.
The label never mentions the door.
That's the four. See you next week.
Rick
From BellyMD
MeNome is our free app for keeping your own record. A minute a day on your gut, sleep, mood, and energy, and over time it shows you what shows up together. It lives at menome.belly-md.com.
I also make MGB+, a small line of gut-brain supplement formulas: Clear, Cool, and Calm, at belly-md.com. Structure-function support, not a treatment for any disease.
If you want to talk through your own gut-brain picture with me directly, I offer a gut-brain consultation (educational, 500 dollars). Details at belly-md.com.
Not medical advice. This newsletter is for education and does not create a physician-patient relationship. Nothing here is a diagnosis or a prescription. Talk to your own physician before starting, stopping, or combining any medication or supplement, including over-the-counter ones.