Iron Deficiency and Anemia: The Most Missed Cause

Iron deficiency is the most common nutritional deficiency on earth, affecting well over a billion people, and it is still routinely missed in people who have already had blood tests. The reason is a single, correctable misunderstanding: doctors and patients both check hemoglobin, see it inside the range, and conclude that iron is fine.

It often is not. Hemoglobin is the last thing to fall, and by the time it does, the tank has been empty for a long while.

What iron actually does#

Iron sits at the centre of the haem molecule inside hemoglobin, where it binds oxygen in the lungs and releases it in tissues. That is its famous job. It is not its only one.

Iron is also central to myoglobin in muscle, to the cytochrome enzymes that run the electron transport chain in mitochondria, and to enzymes that make dopamine, serotonin and noradrenaline. This is why iron deficiency produces symptoms that look nothing like "anemia" as most people picture it: poor concentration, low mood, restless legs, exercise intolerance out of proportion to any blood count, hair shedding, and cold hands and feet.

Those symptoms come from tissue iron depletion, and they appear before hemoglobin drops. That is the whole point, and it is the part that gets lost.

The four stages, and why timing matters#

Most people who feel terrible are somewhere in stages two and three. Only stage four gets flagged in red on a report. Someone who is told "your blood count is normal" at stage three has been given a technically accurate and practically useless answer.

The symptoms, in the order people actually notice them#

• Fatigue that sleep does not repair
• Breathlessness climbing stairs or carrying shopping
• Poor concentration and a feeling of mental fog
• Hair shedding, particularly noticed when washing or brushing
• Brittle, ridged or spoon-shaped nails
• Restless legs at night. An unpleasant urge to move the legs that ruins sleep
• Headaches and light-headedness on standing
• Cold intolerance
• Palpitations
• Cracks at the corners of the mouth, a sore smooth tongue, mouth ulcers
• Pica. A compulsive craving for ice, clay, chalk, paper or raw rice
• Reduced exercise capacity long before any anemia

Pica and restless legs are the two most specific. Pagophagia, the craving to chew ice, is unusual enough that it should prompt a ferritin test in its own right.

What causes it, ranked by how common it really is#

Iron deficiency is not a disease. It is a sign, and the question is always "why".

In women of reproductive age, heavy menstrual bleeding is the leading cause worldwide. A normal period loses around 30-40 mL of blood; over 80 mL is defined as heavy. Nobody measures this, so the practical markers are soaking a pad or tampon within an hour repeatedly, passing clots bigger than a coin, needing double protection, bleeding through onto clothes or bedding, or bleeding for more than seven days. Fibroids, adenomyosis, polyps and clotting disorders sit behind many of these.

The problem is that people compare their periods with nobody. If your mother and sisters all bled heavily, you assume heavy is normal. I have seen women lose the equivalent of a unit of blood every month for a decade and describe their periods as unremarkable.

Other significant causes:

• Pregnancy and breastfeeding. Iron requirements roughly double in the second and third trimesters. Closely spaced pregnancies compound the deficit.
• Gastrointestinal blood loss. Peptic ulcer, gastritis, esophagitis, haemorrhoids, angiodysplasia, inflammatory bowel disease, polyps and colorectal cancer. Regular aspirin and NSAID use increases the risk substantially.
• Poor absorption. Celiac disease is a classic and under-diagnosed cause. So are Helicobacter pylori gastritis, atrophic gastritis, long-term acid-suppressing medicines and previous gastric or bariatric surgery.
• Inadequate intake. Diets low in haem iron, vegetarian, vegan, or simply poor, combined with high intake of tea, coffee, and phytate-rich staples.
• Hookworm and other parasitic infection. A major cause across South Asia, Sub-Saharan Africa and parts of Latin America, and easy to forget in a city clinic.
• Blood donation. Frequent donors can run stores down quietly.
• Intense endurance exercise. Through gut micro-bleeding, foot-strike haemolysis and sweat losses.

The tests, and how to read them#

Two traps are worth naming. First, serum iron on its own is close to useless. It swings hour to hour and rises after a single supplement dose. Second, ferritin is an acute phase protein. A person with obesity, an infection or chronic inflammation can have a ferritin of 60 ug/L and still be iron deficient. That is what transferrin saturation and CRP are for.

Thalassaemia trait deserves a mention, because it also causes a low MCV and is common across the Mediterranean, Middle East, South Asia and Southeast Asia. In trait, the MCV is low but the red cell count is high or normal and ferritin is normal. Treating it with iron for years does nothing except risk iron overload, so the distinction matters.

When low iron needs investigating, not just treating#

This is the section that saves lives, so it is worth being direct.

Iron deficiency in a man of any age, or in a woman after the menopause, with no obvious bleeding source, requires investigation of the gastrointestinal tract. In most health systems that means upper endoscopy and colonoscopy, plus celiac serology. Men do not menstruate and post-menopausal women no longer do, so iron has to be leaving from somewhere, and slow occult bleeding from a bowel lesion is a well-recognized first presentation of colorectal cancer.

The same applies to a pre-menopausal woman whose deficiency does not fit her bleeding pattern, who has bowel symptoms, weight loss, a family history of bowel or gynecological cancer, or who does not respond to adequate iron replacement.

Correcting it properly#

Oral iron works for most people, and the way it is taken has changed. Research on hepcidin, the hormone that blocks iron absorption for around 24 hours after a dose, showed that taking iron every day, or twice a day, actually reduces the fraction absorbed. Alternate-day, single-dose regimens absorb more per tablet with fewer side effects. This is now common practice and worth asking your doctor about if daily tablets are making you miserable.

Practical points that make a measurable difference:

• Take it on an empty stomach if you can tolerate it, or with a small amount of food if not.
• Vitamin C, or a glass of orange juice, improves absorption of non-haem iron.
• Avoid tea, coffee, milk, calcium supplements and antacids within about two hours. Tannins in tea are a major inhibitor, which matters a great deal in cultures where tea accompanies every meal.
• Expect dark, sometimes black stools. This is harmless and expected.
• Constipation is common; fiber and fluids help.

Continue for three to six months after hemoglobin normalizes. Correcting hemoglobin refills the bloodstream. Correcting ferritin refills the warehouse. Stopping at the first is why so many people are back at square one within a year.

Food matters but rarely fixes an established deficiency alone. Haem iron from red meat, liver, poultry and fish is absorbed at roughly 15-35%; non-haem iron from lentils, beans, spinach, fortified cereals and dried fruit at roughly 2-20%, depending heavily on what else is in the meal. Cooking acidic foods in cast iron adds a small real amount.

Intravenous iron is the answer when tablets are not tolerated, not absorbed, or not fast enough, and it is a decision for a clinician who knows your history.

What I actually see in clinic#

The most frequent scenario, by a wide margin: a woman in her late twenties or thirties, exhausted for a year, told her blood count is normal, sometimes told it is anxiety or "just being a mother". Her hemoglobin is 12.3 g/dL. Nobody checked ferritin. When it is finally checked it is 7 ug/L, and when I ask about her periods she says they are fine, then describes bleeding that would empty anyone.

The second: a man in his fifties, treated with iron tablets by three different providers over two years, feeling better each time and then relapsing. Nobody asked why a man was losing iron. That question, not the tablets, is the medicine.

The third, and the one I find hardest: someone whose ferritin is 35 ug/L, technically inside the range, with classic symptoms and hair falling out. There is no clean threshold in nature, and the printed lower limit of many laboratory ranges is set too low to catch symptomatic depletion. A trial of replacement with a clear review point is often more informative than another debate about the number.

At work#

Iron deficiency shows up in occupational health as something else entirely: reduced work capacity, heat intolerance, more errors on repetitive tasks, and slower recovery between shifts. Studies of manual workers have shown measurable drops in physical work output with iron deficiency even before anemia develops, and correction improves it.

Three exposures make it worse. Heat, because heavy sweating and dehydration compound the strain on a reduced oxygen-carrying capacity. An anemic worker in a hot plant tolerates heat poorly and is at higher risk of heat illness. Lead exposure, because lead interferes with haem synthesis and produces its own microcytic anemia, and iron deficiency increases lead absorption, so the two amplify each other. Shift work, because disrupted eating patterns tend to mean tea, biscuits and skipped meals.

For a workforce with many young women, ferritin is one of the few screening tests that reliably finds a fixable problem. In pre-placement medicals for physically demanding roles it is a more useful number than most of what is routinely ordered.

The bottom line#

Iron deficiency causes real symptoms long before it causes anemia, so a normal hemoglobin does not settle the question: ferritin does. Heavy periods are the dominant cause in women of reproductive age and are massively under-reported, so it is worth describing your bleeding honestly rather than comparing it with an assumption. In men and post-menopausal women, unexplained iron deficiency is a reason to look at the gut, not just to hand over tablets. And when you do treat it, treat it long enough to refill the stores, or you will be having the same conversation next year.