This is a three-part series about how getting mysterious black spots on my teeth helped me find out I had an iron disorder, and how I found and tested a novel treatment for it. Parts 2 and 3 will be published shortly.
Disclaimer: This is not medical advice. Talk to your doctor before making medical decisions.
The mystery of the black tooth spots
My first clue that I had too much iron in my body was a complete surprise. I was brushing my teeth in front of the bathroom mirror one morning when I suddenly noticed a huge black spot on my tooth! As I looked closer, I realized I had SEVERAL huge black spots on my teeth which had not been there the month before. I made an emergency appointment with my dentist, who reassured me that the spots weren’t cavities at all, just harmless stains probably caused by changes in my medication or diet.
Cheese + iron = black tooth spots
I’d recently started taking a supplement called lactoferrin, so I typed “lactoferrin black spot teeth” into my phone on the way home from the dentist. Literally the first search result was a letter in the journal of Medical Hypotheses by Ilir Mesonjesi, an Albanian dentist.
His hypothesis was simple: if someone has high levels of free iron in their body, and they eat a lot of cheese, the lactoferrin in the cheese will bind to the excess iron in their saliva and stick to their teeth, creating black spots. He suggested that if dental patients show up with big black spots on their teeth (like me), they probably have one of two causes of high levels of free iron: iron deficient anemia or something called iron overload.
Great, now I had a likely cause for the giant black spots on my teeth: high free iron in combination with a recent increase in lactoferrin. I don’t eat any dairy or cheese (the usual source of lactoferrin), so it would make sense that my black spots only showed up after I started taking a lactoferrin supplement. I stopped taking lactoferrin and brushed my teeth with baking soda to get rid of the black spots.
But why did I have high free iron in the first place? My symptoms didn’t match iron deficient anemia, so I started looking into iron overload.
Iron is a dangerous poison
You’re probably used to thinking of iron as vital to human life, and it is! Without iron, we can’t move oxygen around our bodies and we would instantly suffocate. But iron is also a deadly poison. Free iron reacts with hydrogen peroxide (found in every cell because it is a byproduct of cellular respiration) to create highly destructive free radicals that kill cells. Iron is so poisonous that swallowing only a few grams of iron supplements can kill a person! Despite its toxicity, acute iron poisoning is extremely rare; after the FDA changed packaging requirements for iron supplements in 1997, iron poisoning is now almost non-existent in the U.S.
Our bodies deal with this double bind—needing a deadly poison to survive—by binding iron with special proteins that stop it from reacting with other molecules in dangerous ways. It also limits how much iron it absorbs from food in the intestines: if the body already has enough iron, it turns off iron absorption. If the body needs more iron, it turns on iron absorption, and hopes you eat some food with iron in it soon. (This doesn’t always work, which is why anemia is so common.)
Iron overload can kill
Sometimes genetic mutations cause the “absorb iron” switch to stay stuck on, all the time. In that case, if a person ingests enough iron, their body slowly accumulates more iron than it can safely store. After many years, the body contains so much iron that it can’t store it safely, and the iron begins damaging the body and will eventually kill it. This condition is called iron overload.
The symptoms of iron overload are maddeningly vague and non-specific. They include (in rough order of when they start):
- Joint pain
- Impotence, infertility, amenorrhea, and other signs of low sex hormones
- Low thyroid levels and associated symptoms
- Hypopituitarism (this is a grab bag of seemingly unrelated symptoms)
- Liver failure
- Heart problems
- Grey or bronze patches of skin
- The “iron fist” pattern of joint enlargement in the hand
The symptoms are so varied because excess iron affects nearly every system in the body. The body copes with excess iron in the bloodstream by binding it to storage proteins and shoving it into various organs and tissues: mostly the liver, but also the heart, pancreas, glands, brain, joints, and skin. Too much stored iron causes tissue damage and scarring. These organs and tissues slowly start to fail as healthy tissue is replaced with scarred, nonfunctional tissue. Eventually, the organ damage causes death.
Iron overload is hard to diagnose
Iron overload is hard to diagnose in part because its early symptoms are shared with many other diseases, such as hypothyroidism, rheumatoid arthritis, or hypermobile Ehlers-Danlos Syndrome (hEDS), which I happen to also have. For example, I’ve had fatigue and joint pain since I was 10 years old, which I thought were caused entirely by hEDS. But looking back, I noticed that my fatigue got better when I started taking lactoferrin, and got worse when I stopped the lactoferrin. Without the black tooth spots, I would never have suspected iron overload was contributing to my overall fatigue.
Iron overload is easy to diagnose when someone develops the “classic tetrad” of iron overload symptoms—skin bronzing, diabetes, liver failure, and heart failure. But the presence of these symptoms means they’ve already suffered severe, irreversible damage to the pancreas, liver, and heart.
The internet is filled with stories about loved ones who suffered for years before being diagnosed and/or died of iron overload after doctors missed the early symptoms. Studies show most doctors don’t understand how to diagnose or treat iron overload, leading to an average delay of 10 years in diagnosis after the first symptoms in one study. Ten years is a long time to feel sick and not know why! The “iron fist” pattern of joint problems in the hand is the only symptom unique to iron overload, but it usually only shows up in advanced iron overload, and is hard to distinguish from general joint pain.
Causes of iron overload
Most cases of iron overload are caused by the situation we described earlier, where the “absorb iron from food” switch stays stuck in the on position at all times, which we will explain more in the next section. The other cause of iron overload is acquired hemochromatosis, when a person is massively overexposed to iron through ingesting high iron foods or multiple blood transfusions. For example, one 78-year-old woman developed iron overload after taking a hefty iron supplement every day for 30 years after menopause. A 52-year-old woman with sickle cell anemia developed iron overload after decades of blood transfusions. In a even rarer case, a 19-year-old burn victim needed so many blood transfusions that he developed iron overload after only a few months of transfusions. Most iron overload cases are not caused by acquired hemochromatosis.
Hereditary hemochromatosis (HH) is caused by a collection of genetic disorders that causes the body to absorb iron from food even when it has too much iron already, and is far more common than acquired hemochromatosis. If a person with HH absorbs more iron than they lose, they eventually develop iron overload. How much iron is that? Well, the average U.S. adult eats around 20 mg of iron a day, and only loses a miniscule 1-1.5 mg of iron per day through shedding of dead cells, crying, spitting, etc. Not all of the iron we eat is absorbed, but most people can absorb more iron than they lose while on an average iron diet. So as long as someone with HH is not losing iron in some other way, they will gradually accumulate iron.
If too much iron is so dangerous, why don’t our bodies just get rid of the iron? It turns out that the only “natural” methods for our bodies to get rid of enough extra iron to reverse HH are menstruation and pregnancies, which only some people can do and which are hard to control.
There’s one other method of losing iron: bleeding. That’s why HH is one of the few diseases that is best treated by the ancient and formerly quite popular medical practice of blood-letting (now called “therapeutic phlebotomy” in Western medicine). Today, blood-letting is still the first-line treatment for HH and a few other diseases.
HFE hereditary hemochromatosis
The best-known form of hereditary hemochromatosis, HFE hereditary hemochromatosis (HFE HH), is caused by mutations in the HFE gene, which regulates iron uptake from the intestines. Scientists are currently arguing about whether the most common HFE mutation originated in what is now modern-day Ireland, where 1 in 5 people are carriers of some HFE mutation, or in a Viking population, or in several places in Northern Europe at once. In populations of northern European descent, HFE HH is currently thought to be the most common genetic disease caused by a single gene, with in 1 in 200 people with the genes for HFE HH.
Non-HFE hereditary hemochromatosis
Hereditary hemochromatosis is even more common in some other racial groups: one study of a racially diverse population found that people of Pacific Island and Asian descent had a much higher rate of iron overload than white people, while Black people had nearly as high a rate of iron overload as white people. African iron overload is one form of iron overload found primarily in people of sub-Saharan African descent. It was originally thought to be caused by drinking beer brewed in iron barrels, but only some people who drank the high-iron content beer developed it. It is probably caused by a mutation in the ferroportin gene. Many other forms of iron overload have yet to be characterized. In summary, iron overload caused by HH is widespread among many different racial groups.
Why is hereditary hemochromatosis so common?
Why is HH so common? It’s easy to imagine ways in which people who could store more iron would have an advantage over people who didn’t. Maybe they could have lots of pregnancies without becoming anemic! Maybe they could recover quickly from stabbing each other with spears! Maybe they could lose a lot of blood in childbirth and be back out feeding the pigs next week! Maybe they kept growing during the famine years when everyone survived on rice or potatoes! One study found that people with HFE HH are on average 1-2 inches taller than people without, possibly because they never ran out of iron while they were growing.
At the same time, the disadvantages of HH don’t usually appear until late in life (with the exception of some rarer forms of HH that affect children and infants). It usually takes decades for people with HH to absorb enough iron to start having symptoms, and menstruating people take even longer to show signs because menstruation (and pregnancy) lowers body iron stores. Many menstruating people with HH never accumulate enough iron to be symptomatic before they die of old age-related causes. Even people with HH who don’t menstruate often don’t develop symptoms until after age 40, especially if they donate blood regularly or otherwise lose significant amounts of blood.
In short, HH seems to make people healthier and stronger when they are young, and only sometimes makes them sick when they get older—a pretty good deal most of the time, especially in populations where people died sooner.
Genetic tests for hereditary hemochromatosis
All this was very interesting, but what did it mean for me and my black tooth spots? Dr. Mesonjesi suggested the spots were caused by high levels of free iron in my blood, caused either by anemia or iron overload, in combination with lactoferrin. As someone of northern European descent who has never had anemia or taken iron supplements, I now suspected that I had iron overload caused by HFE hereditary hemochromatosis.
Suddenly, I remembered reading something about hemochromatosis in my genetic diseases report from 23andMe several years ago. I wondered, did 23andMe tell me that I had “the hemochromatosis gene” and I just… forgot?