Iron, Parkinson’s, and Alzheimer’s
Iron in the brain plays an important and perhaps leading role in both Parkinson’s and Alzheimer’s diseases as well as in aging generally. Measured post-mortem, patient’s with Parkinson’s disease had ~200% increase in iron in the part of the brain affected by that disease. (a) The same is true in Alzheimer’s disease.(b) Iron shrinks the brain.
In a mouse model of Alzheimer’s, increased iron coincides with plaque formation, a cardinal sign in that disease; this provides some evidence that iron is causative of plaques.(c)
We usually think of these two brain diseases as somehow inevitable aspects of aging
Does iron lead to cognitive decline, dementia, and brain shrinkage, all on its own? It appears so.
The amount of iron in certain parts of the brain can predict the amount it shrinks over time:
“Striatal Iron Content Predicts Its Shrinkage and Changes in Verbal Working Memory after Two Years in Healthy Adults.”(1)
The accumulation of non-heme iron in the brain has been proposed as a harbinger of neural and cognitive decline in aging and neurodegenerative disease, but support for this proposal has been drawn from cross-sectional studies, which do not provide valid estimates of change. Here, we present longitudinal evidence of subcortical iron accumulation in healthy human adults (age 19–77 at baseline)… Thus, longitudinal evidence supports the notion that accumulation of subcortical iron is a risk factor for neural and cognitive decline in normal aging.
Another study by the same group examined iron in the brain region known as the putamen, and found that “accumulation of iron in the putamen predicts its shrinkage in healthy older adults”.(2)
Since the subjects in these studies were followed over time, it appears likely that increasing iron in the brain was at least partially and maybe wholly responsible for shrinkage in brain volume and cognitive decline.
It’s important to note here that the type of iron that was detected was non-heme iron. Heme is an iron-binding co-factor found in hemoglobin, cytochromes, and other proteins that use iron to catalyze reactions, such as carrying oxygen.
Ferritin is a non-heme protein which doesn’t use iron but merely serves as a storage vehicle.
This is important because free iron, which is iron not bound by ferritin, is the major generator of free radicals (especially the hydroxyl radical, the most damaging type). The measurement of non-heme iron would include both free iron and ferritin.
Ferritin is stored dynamite
So it appears that increased amounts of ferritin, the supposedly safe storage form of iron, can lead to damage, in this case in the brain.
In this situation, ferritin can be likened to a stick of dynamite, which is safe if kept away from heat and flames. That doesn’t mean that you want to keep dynamite lying around your house. Similarly, you don’t want to keep a bunch of ferritin lying around in your brain, ready to release free iron into it because of some untoward cellular event.
How does this brain iron accumulate, and who gets more of it? Another way of looking at it is, who gets dementia, or Parkinson’s?
Obesity and insulin resistance lead to more brain iron
One study found that obesity and insulin resistance are associated with increased brain iron and worse cognitive performance.(3) This makes sense when you recall that Alzheimer’s disease, which is characterized by accumulation of iron (among other things), has been referred to as type 3 diabetes.
All of this leads one to speculate that the (main?) reason that obesity and diabetes cause damage is because they lead to iron accumulation.
Iron is a reactive metal which, unless it’s locked down in the ferritin molecule, generates the dangerous hydroxyl radical, the most damaging of all the free radicals. This is why iron is such a leading candidate for a role in aging and disease: no other element, except perhaps oxygen, is as capable of causing cellular damage, leading to oxidative stress and inflammation, both prominent processes in aging and disease.
We’ve already covered what to do to keep iron levels in the low normal range, which is where you want them.
Use of an iron chelator cut the rate of progression of Alzheimer’s by half.(4) Phlebotomy (bloodletting) lowers body and brain iron stores and has been proposed as a treatment for this disease.(5) I know if I were suffering from it, or from Parkinson’s, I would want this treatment – along with a ketogenic diet, MCT oil, vitamin D, magnesium, and a few other supplements.
Preventing the accumulation of excessive iron in the first place will go a long way toward preventing these diseases of the brain and a decline in brain function.
27 Comments
On the subject of iron and Parkinson’s, Carl Lenore recently did an interview with Dr. Julie Anderson about it – https://superhumanradio.com/shr-1803-replacing-animal-plant-protein-glycemic-control-diabetes-excess-iron-parkinson-s-disease.html (starts at about 57 min).
Carl also gets into iron accumulation and cellular senescence, and the value of donating blood (to reduce iron) at about 1:11 (hr).
Thanks, Stephen. Speaking of cellular senescence, don’t know if you saw the news: Scientists Can Now Radically Expand the Lifespan of Mice—and Humans May Be Next. 25% medial lifespan extension in mice by killing senescent cells.
Reminds me of your post some time back on quercetin for killing those senescent cells.
FYI Hodgon Mill has a white unenriched flour that they say “is recognized for creating healthy foods and is convenient for those on iron-restricted diets.” We can get it here in New England.
Thanks, Joseph.
How is one to regard ferritin levels in a blood test then?
Is eating cheese with meat a good way to reduce iron levels?
I found your post on ferritin and the iron-blocking tips of coffee and tea, thanks.
I checked my multi-vitamin, it has Iron and minerals. Should we buying vitamins without iron?
Yes: https://roguehealthandfitness.com/three-supplements-to-avoid/
Given what you write about iron, do you know of any evidence/studies which show that historical Asian cultures did not have obesity/diabetes despite rice(carbs) precisely due to low iron? I think traditional diet in Asia was green tea, fish, little red meat etc, which would indicate lower iron levels. Paleo community does not really explain that phenomenon, aside from “they ate little sugar/processed foods”.
Regards,
Benas
Benas, while I don’t know of any evidence, I believe that this idea you just elucidated is correct. Traditional Japanese diets, for instance, would be low in iron: tea, fish, rice, vegetables. I also speculate that this might be the case with people who eat lost of sugar and refined carbs without gaining weight: they have lower iron and this better insulin sensitivity. As evidence, I note that people who do this seem to be mainly young, a time in life with low iron stores.
Another piece of evidence is the former lack of the diseases of civilization in undeveloped countries. Those people were much more likely to have low iron or even be iron deficient than in the West.
PS: I was looking around to see if I could find anything about average ferritin in Asia, came across this: https://www.ncbi.nlm.nih.gov/pubmed/20423745 In Korean men and women with normal fasting glucose, ferritin was 85 and 59 respectively. That’s quite a bit lower than the U.S.
I’m reading this differently – 156 for men and 59 for women. Also interesting to note just how much higher ferritin was for men than women, and how (perhaps?) men seem to tolerate more ferritin/iron – e.g. men with 156 had normal fasting glucose, while women with ferritin of 85 already had type 2 diabetes.
Speaking of ferritin – I read it is a protein that attaches to iron, so that the iron molecule is no longer “free” and thus no longer harmful. However, where in the body is ferritin (with iron attached) located? In muscle tissue, brain, organs, blood, elsewhere? Also, is free iron located in the same places/organs as the ferritin&iron bundle?
Yes, you’re right, I misread that figure. Ferritin is everywhere, inside virtually every cell and in blood serum too. If high enough, it gets stored in places like skin and bones. Free iron, ditto. Although free iron seems to be a result of loss of iron homeostasis to some degree, it also appears to be a function of total iron, hence lower ferritin means lower free iron in general.
Understood, thanks! So when an person donates blood, he loses iron that comes from blood (stored in hemoglobin as well as blood ferritin), and then to restore hemoglobin, iron is drawn from both free iron and ferritin located in various parts of the body?
Is there any way to know whether to restore hemoglobin, one will use ferritin-bound iron or free iron, and in what proportions? Also is it possible that certain organs e.g. brain might keep iron and not give it up for hemoglobin production, rendering the donation less effective?
When hemoglobin or other iron-containing components are made, ultimately that iron comes from free iron. Cells will break down ferritin to get it if no other is available.
What you say about certain organs not giving up their iron is correct, to an extent. Once iron gets into some types of cells, it’s harder getting it out. Skeletal muscle might be that way. As far as I know, no tissue holds on to iron permanently. Liver seems to be the main storage tissue, and iron is readily depleted from it.
You Tweeted recently that you think many side effects of “testosterone enhancement therapy” could be mitigated by donating blood. Can you elaborate? I’ve read your posts on iron but am not sure how this would work. I “have a friend” who is starting a cycle tomorrow and who wonders when the best time to donate blood might be, ie before, during, or after a cycle.
Any help appreciated.
Tom, the idea is that HGH and T increase iron levels, and this could be one of the main avenues for harmful effects of both of these. This is a bit speculative, but I think that ensuring iron levels don’t rise much, for example by donating blood, could mitigate much of any damage. As for when to do it, it would be a continuous process, just making sure iron doesn’t rise much, so donating on a regular schedule.
Thanks!
Without supplementing iron, my ferritin was 17 ng/mL. That’s probably because I consume so many things that chelate iron, like tons of green tea and turmeric. Before supplementing and brining my ferritin back up close to 30, which is closer to the lower limit of the reference range, I felt like crap in the late afternoon. Now I feel fine. Is it still a mistake for me to take iron? What do you recommend for someone like me?
So, I don’t know how old you are, but was your doctor interested in your low ferritin? Were you anemic? Do you eat beef and pork? All of these are relevant. If you were anemic, your doctor has a duty to look into the cause, because a frequent cause of iron deficiency anemia in adult, especially older, men, is intestinal bleeding caused by cancer.
I saw a hematologist, and she was concerned and did months of tests and ruled out any internal bleeding or cancer. No iron or blood detected in stool. I had a colonoscopy. Gastro doc was annoyed that it was a waste of time. My WBC is low. It has been for many years. It’s possible my ferritin has been low for just as long. It has only been more recently that I ever tested my ferritin. So, I don’t know what it was before. I always assumed my WBC was low because of my mildy-CR diet. I’m 45.
It sounds like you were anemic, hence the hematologist. A low WBC, if not very low, can be a good thing; shows low inflammation. As for iron supplements, since you’ve taken them already and got your ferritin up to 30, you probably don’t need them any more. (NB, if your doctor wants you to take them, I’m not telling you not to.) How you got anemic in the first place is a good question, since you weren’t bleeding, no cancer, etc. To do that, you’d have to eat no beef or pork, and take tea, coffee, and/or red wine with all meals – and probably something else, like lose some blood. The body just is not designed to become iron deficient; women sometimes do because of blood loss combined with a lousy diet. So I must say it’s kind of a mystery to me.
I already tried stopping the iron, and it fell back down. I have been taking the iron again for a few months. I will get another ferritin test in the next couple weeks and see where it’s at. I supplement with 1 x 18mg ferrochel per day, hours away from any vitamin C. I don’t want my ferritin any higher than adequate. So, if it’s above 30, I plan to cut back. Judging by how I feel, I’m confident it was too low for years. I eat a mildly-CR diet, no red meat, minimal meat of any kind, drink tons of green tea, and eat tons of turmeric and other polyphenols.
Thanks for your input. I was curious what you thought, if there was something else I should do besides taking iron. I could change my diet, but I don’t think that’s a good idea. I think I want to just get barely enough iron that I need. I’ve always known iron to be bad, so avoided it and would never have recommended it to anyone, but now I’m one of those taking it.
Sounds as if you were on an ultra-low iron and iron-inhibiting diet. No red meat, plus all the green tea and other polyphenols. Similar to a regimen Facchini put his kidney patients on – cut death rates in half.