This is a three-part series about how getting 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. In part 1, we learned that the black spots were likely caused by iron overload, a condition in which the body absorbs so much iron that it begins attacking its own tissues. In part 2, we learned about the symptoms and causes of iron overload, and how to treat it using blood donation. We also learned that I had iron overload, but that another medical condition, hypermobile Ehlers-Danlos Syndrome (hEDS), made it hard for me to donate blood.
Disclaimer: this is not medical advice. Talk to your doctor before making medical decisions.
Can lactoferrin treat iron overload?
I was steeling myself to go through 6 – 12 weeks of fatigue and fainting while I donated blood to lower my iron levels, when I remembered what got me into this mess in the first place: taking a lactoferrin supplement, a protein found in milk. Lactoferrin was binding up the free iron in my saliva and depositing it on my teeth, causing black spots. Was it possible that I could use lactoferrin to bind and remove the excess iron from my body, without donating blood?
My theory was that oral lactoferrin would bind to free iron in the intestines and then depart my body in the usual manner of digested food (ahem). I also felt much more energetic and cheerful when I was taking lactoferrin (probably because it bound up the excess free iron in my body) and I wanted to keep feeling good. If lactoferrin lowered my iron levels, it would be a win—win solution.
Apolactoferrin vs. holo-lactoferrin
The first question I had was whether lactoferrin raised iron levels or lowered them, and the answer turns out to be, “It depends.” First, there are two kinds of lactoferrin: apolactoferrin and holo-lactoferrin. Remember, one of the things lactoferrin does is to bind to an iron atom. Lactoferrin that isn’t bound to iron is called apolactoferrin, and lactoferrin bound to iron is called holo-lactoferrin. The two forms can have very different effects.
Holo-lactoferrin (with iron)
Several studies on treating anemia in pregnant people used lactoferrin that was partially bound to iron (30% in one study). It’s not surprising that taking a compound containing iron increased iron levels. Further analysis suggested that the majority of the benefit was not even from the iron bound to the lactoferrin, but that the lactoferrin just mobilized the iron stuck in other parts of the body to the bloodstream, where it could be used to make more red blood cells. The people in these studies may have had more of problem of moving iron around their body rather than a lack of stored iron.
Apolactoferrin (no iron)
Apolactoferrin, on the other hand, is not bound to iron, so it would not add any iron. It would still mobilize iron out of storage and bind to it; the question was what my body would do with it after that. I found studies about using high doses of lactoferrin to help treat hepatitis C, but they didn’t measure iron levels. The only hint I could find was a video from a functional medicine practitioner, Chris Kesser, which mentioned in passing that lactoferrin might work to reduce iron levels. In summary, it seemed likely that high doses of apolactoferrin would lower iron levels but no one had run a study to test it.
Most commercial supplements are apolactoferrin
My next question was, what kind of lactoferrin had I been taking? Had I accidentally given myself iron overload by unknowingly ingesting iron in holo-lactoferrin? I emailed customer support at Jarrow, who told me that, “Virtually all commercial lactoferrin supplements on the market are apolactoferrin,” including the one I was taking.
Update: Taking apolactoferrin with or without food
[Updated 20 February 2020] A reader wrote in to say that a nutritionist advised them that taking apolactoferrin with iron-containing food would bind up the iron in the food and make it more available to the body, while taking apolactoferrin without food would cause it to pull iron out of the body. If this is true, then it would matter how much apolactoferrin and iron you were taking, both total and relative to each other. My guess is that if you are already avoiding eating a lot of iron, it won’t matter if you take the apolactoferrin with or without food.
Apolactoferrin as a candidate to lower iron levels
After my research, I knew that apolactoferrin would mobilize stored iron, and it would not introduce new iron to my body, and it would bind to any free iron it encountered. Given that the alternative was feeling tired and faint for a couple of months, it seemed worth a try! I also wanted to help find an option for the people I mentioned in part 2, who had mild iron overload but couldn’t donate blood and also couldn’t get a doctor’s prescription for therapeutic phlebotomy. If my experiment didn’t work, that was okay—my iron levels were low enough that I wasn’t going to do any permanent damage if I waited a year to treat them in the usual way. And frankly, I was curious and excited to find out if lactoferrin would lower iron levels because I am a giant nerd and I love science.
I talked to my doctor and decided to take 750 mg of lactoferrin a day. We would test my iron levels again in a few months.
Testing apolactoferrin to lower iron levels
About two months after I resumed taking lactoferrin, I noticed that my lips seemed to be getting paler. “I guess I’m getting old,” I thought, “This must be why lipstick was invented.” A couple of weeks later, I noticed that my lips were almost white. I had also started feeling tired again, but in a totally new and different way than I’d ever felt tired before. Finally it occurred to me: I was having the symptoms of anemia!
I scheduled my second iron panel, and the results came back: I was indeed now slightly anemic, and all my other iron levels were in normal range, with 132 ng/mL serum ferritin and 29% iron saturation. I had started at 203 ng/mL serum ferritin and 58% iron saturation, so in only two months I’d lowered my serum ferritin by 70 ng/mL, and my iron saturation had dropped nearly 30%. It was working!
From iron overload to anemia in two months
The good news is that the lactoferrin seemed to be really good at removing iron from my body! The bad news is that I was removing iron from my body too quickly, and my body wasn’t able to make enough new blood cells.
It turns out that this sometimes happens naturally when someone has a chronic disease, and it’s called “anemia of inflammation.” It’s thought that the body is trying to deprive pathogens of the iron they need to grow by temporarily reducing free iron. This also makes the iron less available to make new red blood cells, which results in anemia. (Apparently there’s a reason that chronically ill people in Victorian novels are always pale and out of breath.)
Fine-tuning the lactoferrin dose
Even though I was currently anemic, my serum ferritin showed that I still had plenty of stored iron squirreled away in various parts of my body, and I wanted to follow the advice from the Iron Disorders Institute to lower my serum ferritin to below 75 ng/mL before going into maintenance phase. I lowered my dose of lactoferrin from 750 mg/day to 250 mg/day, and within a couple of weeks my fatigue went away and my lips turned pink again.
Normal iron levels after 11 months
At 4 months, my iron levels had rebounded to slightly above normal and at 8 months, they were still slightly above normal, at 179 ng/mL ferritin and 51% iron saturation. It seemed that 250 mg/day of lactoferrin would maintain my iron levels but not lower them. I increased the dose to 500 mg/day of lactoferrin. After 7 months at this dose, and 11 months after my first iron panel, I finally achieved 75 ng/mL of iron and 38% iron saturation, firmly in the normal range and down from my start of 203 ng/mL and 58% iron saturation. It worked: lactoferrin lowered my iron levels!
Apolactoferrin lowered my iron levels
I succeeded in treating my mild iron overload without donating blood by taking 250 – 750 mg/day of oral apolactoferrin, the form of lactoferrin not bound to iron. Over a period of 11 months, I lowered my serum ferritin from 203 ng/mL to 75 ng/mL. My first iron panel was not until 3 months after I started taking lactoferrin, so there’s reason to suspect that my starting serum ferritin level was more like 275 ng/mL.
I did not lose any significant amount of blood during that time, other than a small amount removed for blood tests. I also stopped taking lactoferrin for a week before each iron panel because I wasn’t sure whether it would affect the test results. I’m continuing to take 250 mg/day of lactoferrin, since it has many other potential benefits and appears to maintain my iron levels at that dose. I will continue checking my iron levels once or twice a year. [Update 2020-09-09: my iron levels rose again, so I upped my dose to 500 mg/day which appears to be a good maintenance dose for me.]
I still don’t know what caused my mild iron overload. I may have hereditary hemochromatosis caused by an as-yet unidentified genetic mutation. Perhaps some odd interaction between my hEDS and my high iron diet caused me to absorb more iron than usual. Maybe I was ingesting some other source of iron without knowing it. Who knows? What I do know is that I feel better with lower iron levels, and I didn’t have to donate blood to get there!
How you can stop iron overload deaths
I wrote up my experience with iron overload and lactoferrin because I thought it was an interesting medical mystery, but also because I want to spread the word about iron overload. Millions of people around the world are at risk of developing iron overload and many people die from it, but few doctors can recognize the symptoms or are willing to run the (cheap, simple, easy) iron panel test to check for it.
If you or someone you know is suffering from iron overload symptoms such as fatigue, joint pain, or hormone problems, you might consider asking for an iron panel (covered by most health care systems). And if you eat a lot of cheese, have black spots on your teeth, and get an iron panel, please think about sending Dr. Mesonjesi an email letting him know the results. (He was super nice—and funny—when I emailed him thanking him for his letter proposing a link between lactoferrin and black tooth spots.)
I’d love to see a formal study on the use of oral apolactoferrin to reduce mild iron overload to see if it works for more people. My experience could just be a fluke, but lactoferrin could also be an easy and cheap alternative to therapeutic phlebotomy or the more toxic iron chelating drugs. It might also be useful in combination with therapeutic phlebotomy to lower iron even more quickly, since it could both mobilize iron out of storage and make it available for building more blood cells more quickly.
If you talk to your doctor and try to lower your iron levels using apolactoferrin, please email me and let me know how it went!
Still have questions? There is now a part 4 answering frequently asked questions!