Hey, folks, been coming across articles talking about how our bad cells crave iron and in fact can cause iron deficiencies by using it up. Many supplements are iron chelators, including turmeric. Anyway, just got iron results back and they are on the very low end of normal. And I am thinking this is good. Any thoughts by you folks? I am on W&W.
Since posting this yesterday, and citing to a study not really applicable, as discussed by Neil below, I am posting the following article entitled "Iron and leukemia: new insights for future treatments." It addresses all leukemias including CLL as needing to soak up iron presenting the thought at least that high iron levels might not be good for us.
The paper you've referenced focuses on acute leukaemias, specifically Acute Myeloid Leukaemia (AML). The authors don't seem particularly familiar with CLL, referring to it as "chronic lymphoblastic leukemia (CLL)".
The sentence "Leukemia cells are dramatically more susceptible to iron depletion than normal cells due to their high requirement for iron to maintain their rapid proliferation. It has been evaluated that treatment targeting iron metabolism induces differentiation of leukemia cells without harm to normal cells.[14]" references an article Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia. (My emphasis)
The only mention of CLL and iron I could find in the paper was "It is reported that overexpression of LCN2 (Lipocalin 2) was found in patients with AML, ALL, CML and CLL [63,64,65,66,67]." and with respect to CLL, that references the paperThe role of matrix metalloproteinase 9 in the pathogenesis of chronic lymphocytic leukaemia. This paper notes that "these enzymes can degrade a number of matrix proteins but are the two main MMPs that digest type IV collagen, the major component of basement membranes. Therefore, these enzymes are potentially important for tissue invasion and remodelling by malignant lymphocytes." The abstract concludes "Our data raise the possibility that MMP-9 modulation may have therapeutic potential in advanced CLL."With respect to the role of iron in DNA synthesis, what I found doesn't provide very encouraging support for your hypothesis, where ion metabolism, including the role of iron in CLL is discussed in this paper.
Targeting metabolic reprogramming in chronic lymphocytic leukemia
"On the one hand, iron is a critical cofactor that is required for DNA synthesis [80]. The transferrin receptor (TfR) contributes to iron import and a higher TfR concentration has been found in CLL directly reflecting the large tumor burden [81]. Leukemia cells harbored TP53 mutation need a mass of iron to support rapid proliferation. P53 plays a role in iron homeostasis and mitochondrial iron homeostasis by modulating iron regulators [82]. Cells may go into canceration or demise when the homeostasis is disrupted [83]. Ferroptosis, a crucial component of p53-mediated tumor suppression, is an iron-dependent form of regulated cell death caused by unrestricted lipid peroxidation and subsequent plasma membrane rupture [84]. The activity of the selenoperoxidase Glutathione Peroxidase 4 (GPX4) is the cornerstone of the antiperoxidant defence [85]. The expression of GPX4 in ferroptosis depends on the presence of glutathione (GSH) [86]. Eprenetapopt, which could reactivate mutant forms of p53 and induce ferroptosis by GSH depletion, is currently being tested in the clinical trials involving patients with acute myeloid leukemia (NCT03931291) [87]. Cysteine availability is the main limiting factor in the synthesis of GSH. The depletion of extracellular cysteine leads to cell death in CLL. Cyst(e)inase, an engineered human enzyme, effectively degrades cysteine and induces ferroptosis in pancreatic ductal adenocarcinoma [86]. The strategy regulating extracellular cysteine levels opens up new therapeutic options for CLL patients with TP53 mutation. Nevertheless, the definitive mechanism that p53 modulates iron metabolism in CLL is unclear. Targeting altered iron metabolic pathway is specific to CLL patients with TP53 mutation." (My emphasis)
Given the paper you referenced focuses on the high iron requirements of acute leukaemias for rapid cell growth and hence the containing cellular membranes, which is where the above paper fits in, I really don't see much relevance to CLL.
I think the only part of the article relevant to some of us is the references to iron overload from regular red blood cell transfusions; "In addition, patients with AL usually receive multiple red-blood-cell transfusions for hematologic support, which aggravates systematic iron overload."
Finally, tumeric doesn't seem to help much, if at all with CLL, unless you know of a later, more promising study than one on 21 CLL patients, which concluded "Our study results suggest that curcumin may be beneficial in a small subset of early CLL patients due to its anti-tumour activity." Due to the study design, even that conclusion is suspect as I explain in How study design influences conclusions - Turmeric miracle revisited
May I suggest that you limit your future research to papers that at least discuss B-cell leukaemias/lymphomas, preferably the chronic Non-Hodgkin Lymphomas? That eliminates studies on about 90% of leukaemias/lymphomas which are not very likely to be relevant to CLL.
Thank you, Neil, for your suggestion. Actually, I was not relying so on that article, which I did not vet adequately as you point out and shouldn't have included. Instead, I have read elsewhere (usually I limit research to ncbi articles and to CLL) about the great need of CLL cells for iron. Hence, this headline seemed to fit the concept I had in my head -- that reducing iron might be beneficial to CLL sufferers. Your extensive quotes include some interesting sounding issues regarding iron but to be honest, it is over my head. So just wondering if anyone knew anything about this iron depletion concept or ever considered it or perhaps this is well known and I've just missed it. And thank you for update on turmeric.
I don't know where you are finding mention of "the great need of CLL cells for iron." I certainly couldn't find any references, so I'd be interested in where you are reading of this?
The possible benefit of turmeric in slowing CLL progression was based on in vitro experimentation (studies of how CLL cells responded to tumeric when observed under a microscope) over 10 years ago. It's a well known issue that obtaining the same effect when you take a supplement has quite a low success rate, due to the problem of achieving a high enough serum concentration to destroy CLL cells without causing unacceptable side effects. That's a particularly serious issue for turmeric, because the liver metabalises it so rapidly. The CLL turmeric trial confirmed that turmeric isn't likely to be of benefit. I'd actually stopped taking turmeric prior to finding that study.
Thank you for that further info. I don't know that what I read said "great need" but something along those lines. If I can retrace where I read it, I'll post it.
If my memory is accurate turmeric and some other natural supplements interfere with the metabolism of medications used for CLL treatment including BTK inhibitors and also Venetoclax.
not sure about the iron issue w Tumeric, however, I take it for the anti-inflammatory benefits. My personal feeling is that a chronic inflammation may have caused my CLL. I can’t base that on any specific research, but frankly it’s the only thing I can think of that may have messed w my immune system!
Just like our current pharmaceutical therapies have side effects, dietary therapies do, too. Cutting iron to starve a single type of cell will result in anemia, which can affect all cells. Our disease itself causes anemia. Obviously that disease-caused anemia does not cure the disease, because the disease continues to progress despite the anemia.
Some day, some biochemist may work out a targeted therapy that affects just our CLL cells, and not our normal B-cells, or other cells. That day gets closer all the time, but is still beyond the horizon.
But read article(s) -- in past couple weeks -- that bad CLL cells need lots of iron (which is why our levels tend to be low, no doubt) and throwing out idea for treatment of keep iron levels low.
The article you cited doesn't talk about iron testing at all. It's all hypothetical. There's no estimate of a benefit if they somehow target the iron uptake, either. In addition, they do not address side effects at all. There's no mention of dietary iron or iron loss seen on standard medical labs due to bleeding.
The article is about future research paths if iron metabolism can be targeted to CLL cells. It's of no practical value at all that Ican see.
If you're clinically below normal on a blood test, then some intervention may help. If you're only at the low end of statistical normal, ask the doctor for what to do if it gets to a clinically low normal. The norms do not by themselves dictate imminent action. But it's good to follow the trend. I don't think iron is regularly tested in most men. I should probably get mine checked.
Just thought this an interesting concept. This medical article, by the way, is speaking to all types of leukemia, specifically including CLL. It is entitled: "Iron and leukemia: new insights for future treatments"
From what I've been coming across, I definitely would not want a high iron level (actually high iron is bad for other disease reasons). It is from these concepts that I am thinking low/normal is perhaps a great place to be on the iron scale.
Vlaminck, this is the same article you posted about. While you say "This medical article, by the way, is speaking to all types of leukemia, specifically including CLL." as I explained in my answer to you, the inclusion of CLL in the coverage by the article is very weak, as it's principally about Acute Myeloid Leukaemia. The authors show their ignorance of CLL by referring to it as "chronic lymphoblastic leukemia (CLL)" Their one reference to CLL is toa paper which concludes "Nevertheless, the definitive mechanism that p53 modulates iron metabolism in CLL is unclear. Targeting altered iron metabolic pathway is specific to CLL patients with TP53 mutation."
The reason for considering having low iron might be advantageous is becauseof its role in DNA synthesis, so theoretically limiting iron could slow progression of a rapidly growing (acute) leukaemia, but CLL is a chronic leukaemia. You still haven't referenced any articles mentioning that "bad CLL cells need lots of iron" and I can't find any, other than the one above, which was inconclusive about the one instance of TP53 mutated CLL where it might have been a possibility.
As SeymourB said "Cutting iron to starve a single type of cell will result in anemia, which can affect all cells. Our disease itself causes anemia." so based on the research you provided, the only situation where starving CLL cells of iron might possibly help is when you have TP53 mutated CLL, and even then science is uncertain. Meanwhile, CLL is likely to make you anaemic and cutting iron intake is probably only going worsen your overall health.
Sorry, didn't realize you were dismissing this article. I don't think this or probably any one or two articles about anything should be grounds to do anything, but I think it raises an interesting concept. I guess we can dismiss it if we aren't convinced it is addressing all leukemias, as it indicates it is, and at some point says lymphoblastic leukemia, but do you really think these authors don't know what CLL is? What's more, this concept makes a certain logical sense given that we CLL sufferers do tend to find our iron levels lowering. N'est-ce pas? I have also read that these bad CLL cells tend to love arginine as well. Food for thought is all. Don't know that articles are all black and white.
And one more thing, I said I am at the lower end of normal levels, not below. Not saying go anemic. But maybe consider whether you want to increase your iron if it is within normal range and your blood count is okay.
By the way, I have been intermittently looking for the article I mentioned that you wanted to see, talking about the BCells wanting iron and have not yet found it. Might only find it when I stop looking. But do wish I could find it. Or maybe I hallucinated it? (Don't think so but I am getting up there).
I agree, this research is of no practical value when we have CLL. Maybe you dreamed about CLL cells wanting iron, given neither of us can find a reference about it. Certainly, I think we've wasted more than enough time on this and it shouldn't change what we do given:-
1) The paper you found states, with my emphasis "This review summarizes physiologic iron metabolism, alternations of iron metabolism in leukemia and therapeutic opportunities of targeting the altered iron metabolism in leukemia, with a focus on acute leukemia.", then goes on to discuss Acute Myeloid Leukaemia
2) As SeymourB has pointed out, it's theoretical; we have no idea of the potential adverse events
3) The one paper reference specific to CLL only mentioned some possible, but uncertain value for those with mutated TP53 CLL
4) If the authors don't know the acronym CLL, they probably aren't that knowledgeable about it
In any case, I recommend that we shouldn't take iron supplements unless on the advice of a doctor. With CLL, low haemoglobin could be due to our CLL, so treating our CLL will address our anaemia, not taking a supplement. Excess iron can cause problems, particularly if we need regular red blood cell transfusions.
There are many cll sufferers who are desperate to find a cure. Its usually a change of diet and exercise. I was diagnosed in 2001 with very low numbers and yet I already had exhaustion. I had 3 fits in 10 days and at a later date the neurologist thought that was the beginning of the cll. Iv never heard that before.I was told that nothing I did would make any difference. I have been reading this site for a long time and nobody has found a change of lifesyle or a food that is a miracle.
I understand it gives a focus and comfort for those who try. I was lucky in that when in the uk Rituximab was added to chemo ie fcr I needed treatment and got complete remission.
When Ibrutinib was agreed in the uk I needed treatment. We had to petition for it but it came along when I needed it. Each time I have had remission and I havent needed another drug.
With all this wonderful science I havent considered eating a restricted diet.
My Dad died age 45 of cll. He was diagnosed 3 years before and already had symptoms. He had boils that wouldnt heal and kept falling asleep at work. They got him diagnosed. I was 43.
My Mum died 6 weeks ago and I am sad that she never got over losing him.
Many of us feel bitter about this disease. Things have changed since 1968. We have hope. Imagine having a way of changing our faulty genes. Ibrutinib is a miracle and because other treatments have come along folk dont know how lucky they are.
Sorry to be such a misery. I feel so sorry about my Mum and losing my Dad aged 10.
It seems there is cancer in so many families and it has made me emotional realising that there will be a cure.
That is so hard, losing your mom so recently. Which of course makes you think of your dad also. I think I still have some mild PTSD from my husband's cancer and death, cancer missed by his GP until too late. I hope you can have a decent tomorrow and be free from negative emotions.
Thankyou. It is hard for you and Im not surprised you feel that way. My Mum was in a carehome and covid stopped visiting several times. I have to accept she has gone. I have heard of several times when cancer is missed. Your whole way of life has changed, Anne uk
Thanks for sharing how 'the good cancer' had such a big and painful impact with such a long reach on you from such a young age (10) and your family. You've personally seen how the three generations of treatments have improved the outcome of survival with CLL; your Dad was probably treated with drugs developed in the 50s, you've benefited from both the second generation improvement of adding the first anti-successful monoclonal antibody, Rituximab to chemo, resulting in chemoimmunotherapy (FCR), which was the first treatment to improve survival time and most recently the first successful inhibitor treatment the BTKi ibrutinib.
I'm sorry a cure hasn't come earlier, but your personal example is giving us hope with proven treatments.
Reading this site is interesting because as those who are newly diagnosed join in, the conversation changes. Now the discussion includes drugs that werent developed or available in the uk 5 or 6 years ago. Who would have thought I could pop a pill instead of chemo. I do need ivig but thats not a problem.
I would like to know why I had really low B12 levels 6 months ago. I have had injections and they were ok 3 months ago. Its strange because I eat a varied diet.
I found this article, interesting because my red blood cells and hemoglobin are good but when they actually do iron test on me, they are far below normal not even on the low end of the chart. My iron saturation is only 18% and my ferritin used to be seven has finally made it up onto the chart at 42. My mother, who also had CLL also had low iron. And was anemic as a child. I have seen a lot of CLL people with low iron and wonder what this does have to do with CLL.
Also almost 18 years ago when I first had CLL, the cancer center checked my iron, and are the ones that told me how low it was, but all these years since I have to ask them about every six years to check it, they don't even care about it. They tell me that my red blood cell and hemoglobin looks fine, think its strange the hematologist doesn't seem concerned about iron. I am totally worn out all the time. And I think it matters.
Thank you, nari. May I ask, did your mother or do you take iron supplements? My understanding is that ID can be quickly turned around with supplementation. Maybe that would help you not be worn out all the time which sounds awful, as I know from when I had a profound reactivation of epstein barr and felt like I weighed 500 pounds. BTW, as with you, I ask for iron tests, not my oncologist, and no one has ever said anything about it to me. My saturation is 20%.
Hello, yes, I did start taking iron again this week, and I have only sporadically taking it over the last several years, 18 years ago when I was first diagnosed I took three tablets a day and it did get my iron a bit up. My mom has been gone almost 25 years now but I don't think she took iron. They really didn't know anything about CLL back when she had it. I see your saturation is low like mine. Also, I am just going to stay on them about checking my iron every few months and I'm going to keep taking my iron pills now. My endocrinologist is actually better with checking my iron when I ask. Yes you'll probably just have to keep on that yourself and see if you can get some better results also. I do know that you're supposed to take iron with no food and orange juice so hopefully they did tell you that. Best to you.
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