Read this one as a snapshot, not as current advice.
Newsletter #6 was written in June 2020 and belonged to a run of issues about depression that does not lift with medication. It leaned on a pair of Australian studies to argue that gluten was a hidden driver of low mood, and it invited readers to ask about gluten testing.
We have kept the question and dropped the parts we cannot stand behind. The original carried several figures with no source attached — how many Americans supposedly have gluten sensitivity, how much celiac disease had risen since 2000, what share of people with depression stop responding to their medication. Those numbers are gone rather than softened. So are its guesses about why gluten might have become a problem (wheat breeding, antibiotics, pesticides), which were presented as theories and remain untested.
One correction is worth stating plainly. The original listed oats among the grains containing gluten. The National Institute of Diabetes and Digestive and Kidney Diseases names wheat, barley, and rye.
Celiac disease and gluten sensitivity are two different things.
NIDDK describes celiac disease as a chronic digestive and immune disorder that damages the small intestine, set off by eating foods that contain gluten — a protein occurring naturally in wheat, barley, and rye. Roughly 1 percent of people worldwide have it, about 2 million in the United States, and many who have it have never been diagnosed.
It does not develop from gluten alone. NIDDK explains that celiac disease occurs only in people who carry particular gene variants, DQ2 or DQ8, and who eat gluten. About 30 percent of people carry one of those variants, and only about 3 percent of them go on to develop the disease. Genes load the question; they do not answer it.
Gluten sensitivity is a separate description. NIDDK notes that someone with gluten sensitivity may have symptoms resembling celiac disease, such as abdominal pain and tiredness, but that gluten sensitivity does not damage the small intestine. The original newsletter was right that this distinction matters.
Celiac disease is also not confined to the gut. NIDDK lists nervous system symptoms — headaches, balance problems, seizures, peripheral neuropathy — among the ways it can show up, alongside fatigue, joint and bone pain, and mental health difficulties.
Do not cut out gluten before you have been tested.
This is the piece of guidance the 2020 newsletter left out, and it changes what a reader should do next. NIDDK states that doctors do not recommend starting a gluten-free diet before diagnostic testing, because removing gluten can affect the results. Someone who quits gluten on their own and feels better has made celiac disease harder to identify, not easier.
Doctors use blood tests and biopsies of the small intestine to diagnose or rule out celiac disease. The blood tests can show antibody levels that often run higher than normal in people with untreated celiac disease. For the biopsy, a doctor passes an endoscope — a flexible tube with a camera — to view the lining of the upper digestive tract and take tissue samples, which a pathologist then examines under a microscope.
If celiac disease is confirmed, NIDDK describes the treatment as following a gluten-free diet, which a doctor will explain and may hand off to a registered dietitian who specializes in celiac disease. NIDDK also advises talking with your doctor before using dietary supplements or any complementary or alternative approach, and going back to your doctor or dietitian if symptoms persist on the diet.
The studies the newsletter cited did not hold up.
The 2020 piece told a story about two trials. In the first, Biesiekierski and colleagues put 37 people with self-reported gluten sensitivity and irritable bowel syndrome on a diet low in fermentable carbohydrates, then rechallenged them. Their 2013 conclusion in Gastroenterology was that they found no evidence of specific or dose-dependent effects of gluten. The newsletter treated that as the finding the media ran with.
The second was the one the newsletter said the media missed: Peters and colleagues, 2014, in Alimentary Pharmacology and Therapeutics. Twenty-two people, three-day challenges of gluten, whey, or neither. Short-term gluten exposure specifically induced current feelings of depression, with no effect on other measures and no gluten-specific gut symptoms. The authors called it exploratory in the title.
What the newsletter could not know in 2020 is how that thread ended. A 2024 international multicentre trial in The Lancet Gastroenterology & Hepatology tested expectancy against actual gluten in 83 people and found that the combination of expecting gluten and receiving it produced the largest symptom effect — a nocebo effect — while gluten alone did not differ significantly from placebo, though the authors could not rule out some additional effect of gluten. A 2025 crossover study in the United European Gastroenterology Journal reported that the symptoms it measured were not gluten-specific, again pointing to nocebo effects and calling for the definition of non-celiac gluten sensitivity to be re-examined.
That is where the honest account stops. A small exploratory signal from 2014 has not been confirmed by larger and better-controlled work since. We are not telling you gluten is irrelevant to how you feel — we are telling you the case the original newsletter built is weaker now than it looked then, and you deserve to know that before changing your diet.
What treatment-resistant depression actually means.
The series this newsletter belonged to was about depression that stops responding. The National Institute of Mental Health puts a definition on it: treatment-resistant depression occurs when a person does not get better after trying at least two antidepressants. The original's claim that half of people with depression fall into this category had no source and is not repeated here.
NIMH also describes why patience is part of the picture. Antidepressants usually take four to eight weeks to work, sleep, appetite, and concentration often improve before mood does, and finding the best treatment may take trial and error. For depression that has resisted other options, NIMH describes esketamine, a nasal spray given in medical settings, which typically acts within a couple of hours.
If a medication is not working for you, that conversation belongs with the person who prescribed it. NIMH is direct about this: talk to a health care provider before starting or stopping any medication. Nothing on this page is a reason to change or stop a prescription, and a diet change is not a substitute for treatment that a clinician is managing.
A provider can also rule out other possibilities with a physical exam, an interview, and lab tests — which is the legitimate version of the instinct behind the 2020 newsletter. Looking for contributors outside the obvious is reasonable. Deciding on your own which one it is, is not.
Questions worth raising when you call.
The original invited readers to write in about gluten testing. We would rather you talk to someone. Gates Brain Health answers at (775) 507-2000, Monday through Friday, 8:00 AM to 5:00 PM, and you can ask about weekend availability. A conversation about your own history will always beat an article about someone else's.
Please keep medical details to the phone or an in-person visit rather than the website. If you are testing for celiac disease, that testing is ordered and interpreted by a medical provider, and the sequence matters — get tested before you remove gluten, not after.
- Have I ever been tested for celiac disease, and was I eating gluten at the time?
- Is there a reason to test before I change my diet?
- How long have I been on this antidepressant, and has it had four to eight weeks to work?
- Who is coordinating my care if I add anything new — my prescriber, or someone else?
If your mood has reached a crisis point.
Do not work through a newsletter for this. The 988 Suicide & Crisis Lifeline runs every hour of every day — call or text 988, or chat at 988lifeline.org. It is free, confidential, and open to anyone in emotional distress, including concerns about alcohol or drug use. When a situation is life-threatening, dial 911 instead.