When Low Iron Won't Resolve: The Hidden Cause

TL;DR: If your iron has been low for years and no pill seems to fix it, that is worth taking seriously, and it is not your fault. One cause that hides for a long time is autoimmune gastritis, where the immune system slowly turns on the acid-making cells of the stomach. The first sign is usually a low ferritin while the rest of the blood count still looks normal, which is why standard care tends to wave it through. It is diagnosed with a simple antibody blood test and an upper endoscopy, it often keeps company with thyroid autoimmunity, and once it is named, it can be managed and watched.

If you have been told your iron is a little low, handed a supplement, and sent on your way more than once, you already know the quiet frustration of a number that will not move. You are tired in a way that sleep does not fix. You may be losing more hair than usual, or your legs feel restless at night. Your doctor keeps saying the labs are "basically normal," and you keep not feeling normal. What I want you to know is that a ferritin that stays low year after year is a clue worth following, and there is often a findable reason behind it.

That reason made headlines recently. Bryan Johnson, who has spent millions measuring nearly everything about his body, shared that after 11 years of unexplained low iron, a careful workup found autoimmune gastritis. If it can hide from the most measured person alive, it can hide from any of us. His story is a useful doorway into a condition that is more common than most people realize and easy to miss.

What is autoimmune gastritis, and why does it hide for years?

Autoimmune gastritis (AIG) is a slow condition in which the immune system attacks the parietal cells, the cells in the upper part of the stomach that make two important things: stomach acid and a protein called intrinsic factor.¹ As those cells are worn down over years, the stomach makes less acid, and that is where the trouble starts, long before anyone feels sick.

Stomach acid does more than break down food. It is what turns the iron in your food into the form your gut can absorb, and it frees iron from the proteins it is bound to.¹ When acid drops, iron stops being taken up well, no matter how much you eat or supplement. Intrinsic factor is the key that lets you absorb vitamin B12, so as it fades, B12 slips too. The pattern is slow and orderly: iron deficiency first, often years before anything else, and B12 deficiency later.²

The disease is silent for a long time because the body is good at hiding it. Most people feel nothing in their stomach at all, with none of the pain or reflux or indigestion that acid-related gastritis brings, which is what separates AIG from the ordinary gastritis most people picture. It is driven from the inside by the immune system, targeting a specific stomach protein called the H+/K+ ATPase, the acid pump itself.⁵ It is also more common than its low profile suggests. Population studies have found antibodies against parietal cells in a meaningful share of adults, with the number rising with age, and most of those people have never been told.⁴

Why is stubborn low ferritin the clue that gets missed?

Stubborn low ferritin gets missed because of how anemia is defined. Ferritin measures your stored iron, the reserve in the tank. Hemoglobin measures the iron circulating in your blood right now. When iron runs short, the body drains the reserve tank first to keep hemoglobin looking normal, so you can be truly iron deficient with a ferritin near the floor and a hemoglobin that reads "fine."

That is the gap where autoimmune gastritis lives. The lab that defines anemia looks acceptable, so nobody asks the next question, which is why the reserve tank will not refill. A ferritin of 15 or 25 gets a shrug and an iron pill. Bryan Johnson's ferritin averaged 38 for over a decade, a number many labs flag as within range even though it sits below where I want my patients. His hemoglobin was normal the whole time, which is why the low iron kept getting explained away rather than explained.

At Fishtown Medicine, a ferritin that stays low is treated as a question worth answering. We aim for a ferritin above 50 ng/mL for most people, well above the bare minimum a lab calls acceptable, because the space between "not anemic" and "well stocked" is where fatigue, hair shedding, and restless legs live. Our guide on iron, heavy periods, and hair loss walks through the ferritin targets in more depth. The other tell is iron that will not respond to oral supplements. If you have taken iron faithfully and the number barely moves, that refractory pattern is itself a signal, and unexplained iron deficiency that resists treatment is one of the strongest reasons to look for autoimmune gastritis.³

What does Bryan Johnson's diagnosis show about doing the basics first?

Bryan Johnson's case shows two things at once, and both are worth sitting with. The first is that even a person tracking hundreds of biomarkers can carry a hidden condition for over a decade, which is a humbling argument for reading the basics carefully rather than chasing the exotic. His team found it the ordinary way, by refusing to accept "low iron for unknown reasons" and following it to an upper endoscopy with biopsies and an antibody test.

The second is a note of caution about experimental medicine, and here I want to be careful and fair. It would be easy to point a finger in a single direction. Bryan had used rapamycin, a powerful immune-modulating drug borrowed from transplant medicine, for about 5 years before he stopped it. But his own records tell a more careful story: his iron had been low for roughly 11 years, which is years before the rapamycin ever started. The timing does not fit a simple cause, and the more likely thread is his long history of autoimmune thyroid disease, since stomach and thyroid autoimmunity travel together often enough to have earned a name, thyrogastric syndrome. I am not here to second-guess his team or to assign blame.

What his story does reinforce is why we do the fundamentals with rigor before anything experimental. Rapamycin blocks a growth pathway called mTOR and has promising longevity signals in animals, but it also carries trade-offs Bryan described himself: recurring skin and soft-tissue infections, higher blood sugar and lipids, and a faster resting heart rate. Pushing the edge of what is possible is valuable, and one person experimenting in the open teaches the rest of us something. It also carries costs that are hard to predict, which is why movement, nutrition, sleep, and a thorough diagnostic base come first, and why we treat experimental compounds with patience and a lot of monitoring. Our read on rapamycin, the signal and the noise goes deeper into that balance.

Does a tightly controlled life change how the immune system learns?

There is a second idea worth holding lightly here, and I want to label it as a hypothesis rather than a settled fact. The immune system learns partly through exposure. People raised around pets, farm animals, soil, and a wide variety of foods tend to develop fewer allergies and, in some studies, fewer autoimmune conditions, an observation called the hygiene hypothesis. The thinking is that an immune system with too little to engage can turn its attention inward.

I find the idea compelling, and it is worth saying plainly that it has not been shown to cause autoimmune gastritis. AIG is driven by specific immune cells attacking a specific stomach protein, and it runs strongly in families and alongside other autoimmune diseases. A very curated life did not, on the evidence, give Bryan Johnson this condition. Where the idea is useful is in the safe, everyday version of it: a diverse microbiome fed by fermented foods and a wide range of whole foods, regular time outdoors and in contact with nature, life with pets, and a home that is not scrubbed sterile. That is different from eating spoiled or old food, which I do not recommend, and it is not right for everyone. People with mast cell activation syndrome (MCAS) or histamine sensitivity often do better with fresher, lower-histamine foods, so this is a place where personalization matters. Our guide to immune resilience covers the broader picture.

How does Fishtown Medicine work up iron that will not come up?

At Fishtown Medicine, iron that will not come up is more than "low iron." We treat it as a thread to pull, because the reason usually points somewhere specific, and finding it changes the plan. The workup follows the biology of the problem rather than a checkbox.

We start by reading the basics the way they deserve to be read. A ferritin below our target with a normal hemoglobin is a finding worth chasing, and our guide on what your blood count reveals explains how much a careful CBC can and cannot tell you. From there, when the iron is stubborn and unexplained, we look for the causes standard care skips: blood loss, celiac disease, and autoimmune gastritis. For AIG specifically, that means anti-parietal cell antibodies and intrinsic factor antibodies on a blood draw, a gastrin level and pepsinogen ratio to gauge how the stomach is working, and, when the picture calls for it, an upper endoscopy with biopsies from the right part of the stomach, which is the only way to confirm it. Because AIG and thyroid autoimmunity travel together, we check the thyroid too, the same way we do in our guide on thyroid antibodies with a normal TSH.

Treatment then matches the mechanism. If the stomach is not making acid, oral iron often will not absorb well, which is why intravenous iron is sometimes the kinder and faster route, and why we change course instead of prescribing pills that cannot work. We replace B12 before it ever reaches the level that causes nerve damage. And because long-standing autoimmune gastritis carries a modestly higher long-term risk of stomach growths, we set up appropriate endoscopic surveillance rather than leaving it unwatched. Whether you are around the corner in Fishtown or Port Richmond, or coming across the Ben Franklin Bridge from Cherry Hill or Haddonfield, the goal is the same: find the reason, treat the mechanism, and keep an eye on what needs watching.

Guidance from the Clinic

"The line I keep coming back to is that the absence of symptoms is not the presence of health. A ferritin thats been low for years while everyone calls it normal is the body telling you something early, and my job is to listen to it before it becomes anemia or a B12 problem or worse. I dont want anyone to leave with a pill and a shrug. If your iron wont come up, lets find out why together, because there almost always is a why."

Related at Fishtown Medicine

• Iron, Heavy Periods, and Hair Loss - the ferritin connection and the targets we aim for
• Thyroid Antibodies but Normal TSH? - catching autoimmunity early, the same pattern in the thyroid
• Tired for Months, Labs "Normal" - the workup a 12-minute visit misses
• What Your Blood Count Reveals - how to read a CBC with careful attention
• GERD and Gastritis - the acid-related forms, and how they differ
• Rapamycin: The Signal and the Noise - rigor before experimental longevity compounds

Scientific References

1. Kulnigg-Dabsch S. "Autoimmune gastritis." Wiener Medizinische Wochenschrift. 2016;166(13-14):424-430.
2. Hershko C, Ronson A, Souroujon M, Maschler I, Heyd J, Patz J. "Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion." Blood. 2006;107(4):1673-1679.
3. Hershko C, Hoffbrand AV, Keret D, et al. "Role of autoimmune gastritis, Helicobacter pylori and celiac disease in refractory or unexplained iron deficiency anemia." Haematologica. 2005;90(5):585-595.
4. Zhang Y, Weck MN, Schottker B, Rothenbacher D, Brenner H. "Gastric parietal cell antibodies, Helicobacter pylori infection, and chronic atrophic gastritis: evidence from a large population-based study in Germany." Cancer Epidemiology, Biomarkers and Prevention. 2013;22(5):821-826.
5. Toh BH, Sentry JW, Alderuccio F. "The causative H+/K+ ATPase antigen in the pathogenesis of autoimmune gastritis." Immunology Today. 2000;21(7):348-354.
6. Vannella L, Lahner E, Osborn J, Annibale B. "Systematic review: gastric cancer incidence in pernicious anaemia." Alimentary Pharmacology and Therapeutics. 2013;37(4):375-382.