Iron: the most under-appreciated mineral in the body?

Dr David Fraser:
Yes, it is. Yes. Yes, definitely. Iron plays a number of roles in the body, but probably the one that’s most widely recognised is its role in the formation of haemoglobin. That’s the red pigment that we have in our bloodstream and it’s packaged up into red blood cells and we have obviously quite a lot of them – about 5 billion of them per mL of blood. The haemoglobin picks up oxygen in the lungs and delivers it to the cells. So it’s very important in oxygen delivery and transport around the body. But iron also plays a role within the cell in organelles called mitochondria, which are involved in energy production. So it’s one of the reasons that if you become iron deficient, you lose energy, you become lethargic and fatigued, is because iron plays such an important role in this aspect of our lives.

Clare Blake:
That’s getting low iron and then the other side is high iron levels.

Dr David Fraser:
Yeah, it’s kind of a double-edged sword, I guess, and the body has to play a real balancing act there where if you have too little iron, you become iron deficient and you become lethargic and you don’t have enough iron for what you need. If you have too much iron as well… Iron is an atom that is highly reactive. So it can form free radicals, which can damage cells, DNA, and cause all sorts of complications as well. So the body’s got to really tightly [balance] so we’ve got enough of what we need without developing the problems of having too much iron.

Clare Blake: 
What’s the best way to get iron?

Dr David Fraser: 
Well, the best way of getting iron is in our diet. So it’s a nutrient. We absorb it from the food that we eat. Most of the iron would come from sources such as meat. That’s probably the most common source that we have, but there’s also vegetable sources as well. In a lot of cases, if someone’s iron deficient, they’ll be put on iron supplements instead, just because they’re probably not getting enough from their diet.

Clare Blake:
How quickly can you bring it up?

Dr David Fraser: 
It depends how you do it. If you’re taking an iron supplement … and it obviously depends on how iron deficient you are. So if you’re quite iron deficient, your body will have a drive to absorb more iron and it would probably go up relatively quickly in the short term, but then it’ll slow down because the body self regulates how much on you get from your diet. By far the quickest way of getting iron in is to get an iron injection, of course, because it goes straight in and you’ve got all your iron there.

Clare Blake: 
If our diet’s not right, how quickly can it go down?

Dr David Fraser:
The body is actually pretty good at maintaining iron levels. So it does take a while to lose that iron. We don’t actively excrete iron. So we lose it in things like the sloughing off of skin cells and cells on the lining of the gut. The other way that we will lose a lot of it, but this is particularly important for young women is menstruation, a major source of iron loss for women.

Clare Blake: 
We’re better at hanging onto other more precious minerals really. I know when it comes to iron, we just don’t see the value in it.

Dr David Fraser:
Unfortunately, it’s really common. I can remember giving a talk in Manila at one stage to a whole heap of doctors over there on iron deficiency and they said they would have patients coming to them, who would say, “I’m really feeling really bad.” And they were worried about it. They’d find out they’re iron deficient and go, “Oh, is that all?” Unfortunately it really affected their lifestyle. I can remember having a colleague of mine, I gave a talk on iron deficiency and she came up to me after and she said, “Oh, so it’s really important. Should I get myself tested?” And I said, “Well, look, you’d be in a high-risk group, so have yourself tested and see what happens.” She got diagnosed. She was that iron deficient that they injected her pretty much immediately with iron, and two to three weeks later she came up to me and she said, “I’ve never felt this good.” So she was someone who was overworked, she had kids she was looking after, she was working hard and just thinking she was just run down because of that. But she was iron deficient and that was the major thing that was happening to her.

Clare Blake: 
Hanging on to iron during pregnancy is pretty tough, but I believe you can stockpile it.

Dr David Fraser: 
Well, you can, yes. The problem with pregnancy is the placenta and it’ll really suck the iron out of a pregnant woman. So, the foetus basically acts as a parasite.

Clare Blake: 
Very successful parasite.

Dr David Fraser:
It’s a very, very successful parasite, definitely. And towards the last trimester of pregnancy, it’s almost impossible to get enough iron from the diet. So the placenta is just sucking it out of you so fast that you just can’t replace it. So really, that’s when you draw on your iron stores. And the World Health Organization has suggested that in order to get through pregnancy without having to rely on really high iron supplements, you should have at least 500 milligrams of storage iron in the body. Unfortunately, most women, even in a place like Australia, just don’t have those iron stores.

Clare Blake:
And before you decide you’re low, because you’re feeling tired, you should really consult a doctor. I should say that all the information here is general in nature and not personalised. You should always seek your own medical advice about your personal circumstances.

Dr David Fraser:
Definitely. Most definitely. And one of the reasons is that, as I said before, iron deficiency will lead to fatigue. You’re feeling run down. There’s a very common disorder, haemochromatosis. It affects about one in 180 Australians. It’s an iron overload disorder. It’s genetic, but the symptoms at least early on are pretty much exactly the same as iron deficiency.

Clare Blake:
Really?

Dr David Fraser:
So fatigue is one of the most common symptoms of haemochromatosis. So you can imagine someone who says, “Look, I’m a bit run down. I think I must be iron deficient,” goes and takes an iron supplement, they could actually be making the situation worse.

Clare Blake:
Let’s talk about haemochromatosis. You found the gene around the ’90s responsible for haemochromatosis, but it’s been diagnosed a lot earlier than that.

Dr David Fraser:
Oh, for sure. We’ve known about haemochromatosis for a long time. I guess one of the issues is what we didn’t know is just how common it was. I think prior to the gene being discovered, we did know that it was common, or people who were at least researching in that area and doctors, clinicians who knew about haemochromatosis, did realise how common it was. But discovering the gene that was affected really showed us just how common it was. So in Australia, you are talking about one in 180 people as I mentioned before. It’s a recessive disorder so you need two copies of the mutant gene, which means if you have one copy, you’re a carrier. So while you may not have symptoms, you can still pass it onto your children. And the carrier frequency in Australia is about one in eight to one in 10. So quite a lot of people are walking around with that mutation and just don’t know it.

Clare Blake: 
What is the disease?

Dr David Fraser:
The disease is iron loading. So basically what happens is your body thinks it’s iron deficient and so it absorbs more iron, it deposits in the tissues and that extra iron causes all sorts of problems. The most common problems as I said, at least to start off with, are lethargy. The buildup of iron mainly occurs in the liver and what you’ll get there is liver disease. So if it’s untreated, it can lead to liver failure, liver cancer, all sorts of problems there, but diabetes is common in the disorder and also arthritis. You can get a bronzing of the skin. These are all when the disease has progressed quite a long way. These days, it tends to be diagnosed a lot earlier, but not always. It’s one of those things, I can remember talking to the father of one of my daughter’s friends. We [were] just talking after school when we were collecting the kids. He asked me what I did and I told him what I did and he goes, “Oh, have you ever heard of haemochromatosis?” And I said, “Well, yes, I have heard of that one.”

Clare Blake: 
Funnily enough.

Dr David Fraser: 
That’s right. But it turns out he had haemochromatosis. He was diagnosed early, but he was in his thirties when he had to have a hip replacement and that was due to the arthritis caused by haemochromatosis. Whereas had he been diagnosed earlier, that iron could have been removed and he wouldn’t have had any of those problems.

Clare Blake: 
But if you don’t know it’s in your genetic history, the symptoms are pretty vague so it is tricky to diagnose.

Dr David Fraser: 
It is, but it’s getting better because these days if you were to go to a doctor and say, “I’m feeling run down.” “I’m feeling tired.” One of the first things they’ll do is they’ll do a blood test for haemoglobin levels and normally they’ll do iron status as well.

Clare Blake: 
Will they ask you about your heritage because that gene comes from a certain part of Europe traditionally, doesn’t it?

Dr David Fraser:
Yes, it does. Yes.

Clare Blake: 
So if you’re from the UK, Ireland…

Dr David Fraser: 
Yes, definitely. Definitely. It is far more prevalent in those areas. It’s got a celtic origin and it’s thought the Vikings spread it far and wide in their pillage and plunder sort of lifestyle that they had there. Multiculturalism just means that the genes can spread a bit more nowadays. But yes, it is mainly on that background. But like I said, what they’ll do is they’ll test you for your iron levels because like I said, the most common cause of, or maybe not the most common cause, but a very common cause of feeling tired and rundown is going to be either iron deficiency or iron loading. So it’s one of the first things they’ll look at. And they’ll pick that up then if they see an abnormality where you’ve got a high level of iron, they’ll actually go and screen you genetically to see whether you do have the mutation and from then on, put you on some sort of treatment. The common treatment these days, or the only treatment really these days, is what we call phlebotomy, which is basically removing blood. Haemoglobin contains a lot of the iron in your body. So by removing blood, we’re actually removing iron.

Clare Blake: 
And then it forces your stores to release some into your bloodstream.

Dr David Fraser: 
That’s right, yes. Depending on when you’re diagnosed and how iron loaded you are will depend on how often you need to be phlebotomised during that de-ironing phase.

Clare Blake: 
So for example, initially you might have to have it maybe once every couple of weeks and then when you get it under control, less and less, maybe a couple of times a year?

Dr David Fraser: 
That’s it. Yes, yes. Like I said, it depends on how early it’s going to be diagnosed. So if you were to diagnose someone very early, I know I was doing a speaking tour of schools last year, and I mentioned haemochromatosis and these were to high school kids. And there was a kid in the audience who said, “Oh, yes, I know about it.” And I asked him how, and it turns out he had it. He discovered that he had haemochromatosis because there was a family history of it. His uncle or someone like that got diagnosed. So they screened everyone in the family. So he was found pretty much before he developed iron loading. So really all he has to do is monitor his iron levels and he can get phlebotomised when they get to a too-high level. He may never have to be de-ironed. And so because of that, he’ll probably never have any of the symptoms at all. Whereas in the person I was talking about before, who had the hip replacement, he was diagnosed too late and so the damage had been done and that was the problem. So the earlier we can diagnose people with haemochromatosis, obviously the better it is for them.

Clare Blake: 
Given that a lot of our population comes from that part of Europe. Shouldn’t it be part of a screening process?

Dr David Fraser: 
That would be great, yes. There have been studies that have suggested that that would actually be cost effective as well in a place like Australia.

Clare Blake: 
The treatment is just removing a bit of blood. There’s no medication, very little side effects. But big pharma are looking at other solutions.

Dr David Fraser: 
People don’t like being jabbed with needles, and I can completely relate to that. But also we have some people when they’re diagnosed… I remember talking to one patient when I was doing some talks at a patient group. When he was first diagnosed, he was really iron loaded and he had to have a bag of blood drawn every two weeks for five years. That’s five years of his life that he was completely exhausted for because he was constantly losing blood. And that’s how much it took to de-iron in that person. Obviously he was so iron loaded that he had a lot of irreversible damage there done as well. So liver disease, plus arthritis and so when I was talking to him, he really still wasn’t in a good way, but his iron levels were under control at that stage.

Clare Blake: 
If you are treated early, then you can live a completely normal life, no other effects?

Dr David Fraser: 
As far as we’re aware. The studies really haven’t been done to prove that conclusively but as far as we’re aware, you can pretty much overcome just about every side effect of haemochromatosis if you can stop the iron loading in the first place.

Clare Blake: 
When you say that liver disease, it’s really common with undiagnosed haemochromatosis. I think about uncles and cousins and people in my family that apparently died of liver cancer that didn’t drink and they had a bit of an associated stigma, it’s like, “Oh, he reckons he didn’t drink.”

Dr David Fraser: 
That’s right. A closet drinker, a closet alcoholic. Definitely. They have found that when someone has been diagnosed with haemochromatosis and they go back through, they screen relatives and they find a couple of other carriers. And then if they look back through the family history, there is a lot of times where they’ll find a great grandfather or an uncle who did die of something associated with the liver. It was probably suggested that they were closet drinkers and in fact they had iron loading.

Clare Blake:
Clear their name at last. Iron has been linked to other conditions. I don’t know whether there’s any evidence to suggest that.

Dr David Fraser: 
Iron is involved in a number of other conditions, definitely. One of the most common ones that we know of is beta thalassaemia. This is a condition where the body doesn’t produce red blood cells properly and so it responds to that by trying to produce more red blood cells. And the result of that is that because red blood cells contain a lot of iron, the body gets fooled into absorbing more iron than it needs. So these patients with beta thalassaemia do become iron loaded, to varying degrees because it’s a disease that has a wide spectrum going from something that’s almost asymptomatic up to something that’s quite a severe life-threatening disorder. It’s a genetic disorder, but it’s also really common. So if you go to places like Cyprus, you’ll find that about 16 per cent of the population has beta thalassaemia. So it’s quite amazing how highly prevalent it is.

Clare Blake: 
Is it common here?

Dr David Fraser:
Not so much. Unlike haemochromatosis where it’s more prevalent in the caucasian population, beta thalassaemia is more prevalent in places like southeast Asia, across the Middle East and in southern European countries.

Clare Blake:
And it’s dangerous?

Dr David Fraser: 
At its worst, it can be life threatening for sure. And those people that have beta thalassaemia major actually require blood transfusions probably every two weeks or so. And they’re also on iron chelators to remove the iron that’s delivered from that blood.

Clare Blake: 
Your group is also working on research about the link between iron and depression. Now that’s also very early days, isn’t it?

Dr David Fraser: 
Yes. That’s something we’ve only just been looking at recently. We’re still trying to get funding to pursue that. The idea behind that is that, obviously, being iron deficient does make you feel run down and there have been some studies that have shown that treating patients for their iron deficiency can actually increase their mental health as well. So it stands to reason that it could work the other way that people who… we’re not saying that iron deficiency is the cause of depression, but potentially it may be something that influences someone and can potentially tip them over the edge into depression. Like I said, very early days, we don’t know whether there will be a link there, but it’s something that we’re exploring.

Clare Blake: 
It makes sense that somebody who’s depressed is probably also not likely to be eating properly as well.

Dr David Fraser: 
That’s true. It’s likely that someone who is depressed is potentially lacking a whole range of nutrients. But as I said, we’re going to start with looking at iron levels and see if we can find a relationship there. As I said, very early days. So not something that we can make any statements about at the moment.

Clare Blake:
We talked about high iron and low iron, and once you’ve been diagnosed with low iron, then what’s the best treatment?

Dr David Fraser:
As far as iron deficiency goes, the most common treatment we use would be iron supplements. I’m sure most pregnant women would be well experienced with them. Unfortunately, the ones we’ve got on the market at the moment are based on ferrous salts. Ferrous iron’s quite reactive and so there are a number of side effects associated with the supplements that are out there now which cause around 50 per cent of people to actually stop taking the supplements, which is a bit of an issue, especially for pregnant women, because they’ve already got enough on their plate. You give them a tablet that’s going to make them feel a bit sick, it’s not a good thing. So one of the things we are working on is trying to develop better supplements. We’ve got a number of companies that we’re working with where they’ve made a different form of iron, which by right should reduce the symptoms.

Clare Blake: 
Can we talk about those complications? I know constipation is one of them.

Dr David Fraser: 
Yeah. Your gastrointestinal side effects are the main ones. There’s also evidence that it may be able to affect what we call the microbiome, which is the bacteria that we have living in our intestine. Now, most people think of bacteria as being something that’s bad, but we also have friendly bacteria living in there too. And people would be familiar, I’m sure, with probiotics. Having a lot of iron all of a sudden go through the intestine, there is some evidence at least that it can affect the way those bacteria act and the type of bacteria that are there. And we really have no idea what effect that might have. We know that for instance, the microbiome during infancy can affect things like neurological development, immune system development. It’s one of those fields that we really don’t know too much about yet. But if you added iron into that mix and potentially change things, there could be complications there, or there could be implications there of that iron. But as I said, we really don’t know what those effects might be at the moment. But we think that making something that has fewer side effects is obviously going to be a better thing.

Clare Blake:
Let’s talk about hepcidin then. That’s at the centre of this, your research, isn’t it?

Dr David Fraser: 
Yes. Hepcidin is a small peptide that’s produced by the liver and it’s often termed the master regulator of iron homeostasis. So what it does is it stops iron being released from cells. So the more hepcidin you have in your bloodstream, the less iron gets released. And that includes from the intestine. So if you stop release from the intestine, you actually stop iron absorption. So we were the first group back in 2003 to show that the reason that haemochromatosis patients load with iron is that the mutation that occurs in the HFE gene actually feeds back and decreases hepcidin expression. So that’s why they load more. What we don’t know is how HFE connects to hepcidin yet and that’s something that we’re actively researching as well. Because if we can figure that out, we might be able to come up with some better treatments.

Clare Blake: 
Let’s talk about iron and getting it in the natural way. Who needs it? How do we get it? And what’s the best way?

Dr David Fraser: 
Well, the people who need most of the iron are premenopausal women. They have higher iron requirements than men and post-menopausal women. The current recommended daily intakes for men are generally met by the diet. Men don’t have to be concerned about iron deficiency all that much. It’s premenopausal women that is the most at risk group of iron deficiency. The current recommended daily allowance is 18 milligrams. Whereas most women would probably only take in about 12 milligrams a day, which means that they’re lacking iron. As I said before, in order to get through a successful pregnancy, the World Health Organization suggests that women should have about half a gram of iron as storage iron. Now, when we’re talking about serum ferritin levels, and that’s a level of about 60 to 70, as far as serum ferritin goes, whereas most women in Australia would be far less than that. Really I think premenopausal women should be looking at getting their iron levels tested, especially if they’re looking at becoming pregnant, because that way they can make sure their iron levels are okay. Now there are a number of ways you can get extra iron in. The most common way is to take an iron supplement. The high-level iron supplements are the ones that cause most of the side effects, but it is possible to get lower level ones, 10 to 20 milligrams. They’re not going to be much good if you’re actually iron deficient, you do need those high levels. But if you’re just trying to maintain your iron levels then taking something like that can help. If you are severely iron deficient these days, they tend to inject you with iron instead.

Clare Blake: 
How do you get it in your food?

Dr David Fraser: 
Well, it’s meat that’s the main, it’s going to be one of the main sources of iron or readily absorbable iron anyway. It’s commonly thought that meat iron is more bioavailable, so easier to absorb than iron from vegetable sources. But it’s possible to get iron from quite a number of things and that’s why I guess that vegetarians and vegans are more at risk than someone who’s an omnivore. Now that doesn’t mean that a vegetarian or vegan diet can’t be healthy, it just means you’ve got to be much more careful about what you eat to make sure that you do get enough iron in.

Clare Blake:
It’s fascinating research, and we wish you the best of luck in the future. And if you’d like to keep up to date about Dr David Fraser and his work, and all our latest research at QIMR Berghofer, just go to qimrberghofer.edu.au. Thank you David.

Dr David Fraser: 
Thank you very much.