Curcumin and iron

July 19th 2008 post. Our bodies need iron in order to function normally, but too much iron can increase the risk of developing cancer by promoting free radicals, and let’s also not forget that, once you have cancer, your cancer cells eagerly gobble up this metal, which is essential to their growth and wellbeing.

But too little iron can lead us to develop anaemia, which is one of the markers of active myeloma. Anaemia, in fact, is the “A” in the acronym “CRAB.” Can’t have too much..can’t have too little…

It just so happens that, according to my most recent (April) test results, my serum iron and ferritin (ferritin, by the way, is a protein that binds to and stores iron that the body can use when needed) are the lowest they have ever been, as far as I know. In May I went to see my fabulous family doctor who didn’t see that as a sign of the myeloma kicking up any dust. No worries. What is important, he remarked, is that my haemoglobin and haematocrit are normal (they are). By the way, he was very pleased with my overall results. So am I.

He told me to take an iron supplement to increase my serum iron levels, but, as stubborn as an Alpine goat, I decided to wait for my next test results (still haven’t taken them, by the way). The reason for my stubbornness will be clear at the end of this post.

I should mention that I have been intending to write about curcumin and its effect on body iron for quite some time now, but other things have been getting in the way. Today I was finally inspired to look over a draft that I wrote back in March (!), when an Italian blog reader (grazie!) left me a comment pointing to a study on curcumin that might provide an explanation for my low iron levels. Sherlock did not have access to that particular journal, but she was able to hunt down and send me a couple of other studies.

The first study deals specifically with curcumin and iron. It’s titled Iron chelation in the biological activity of curcumin and was published in “Free Radical Biology & Medicine” in 2006. You can read the abstract here: http://tinyurl.com/3q9zzu

But first, what is iron chelation? The body cannot metabolize some heavy metals such as mercury and lead, and an accumulation of too much of this stuff can cause toxic effects, interfere with regular body functions etc. Heavy metals can be removed from the body using what are called chelating agents that bind to metals, hold on tightly to ‘em and finally expel them.

Apparently that is what curcumin does. As we can read in the above-mentioned abstract, ferritin protein levels decreased in cultured liver cells when curcumin was present. And Mice that were fed diets supplemented with curcumin exhibited a decline in levels of ferritin protein in the liver.

And now for a look at the full study, without overloading the post with details that I can barely grasp myself. The first part examines the well-known chemopreventive action of curcumin, so skip skip skip.

Then we get to the ferritin-iron-curcumin discussion. The jargon in this part is quite convoluted, hard to translate into simpler language. I did my best. Oh, before I forget: I skipped the part about the increase in GST, or glutathione S-transferase, in cultured liver cells, since that would have made this post way too long. But if you are interested in GST, let me know, and I will be glad to forward the entire study to you. Back to business, now.

The researchers suggest that iron chelation may be a novel mechanism that contributes to the potent cancer chemopreventive activity of curcumin. In their tests, curcumin activated IRPs, or iron regulatory proteins. These thingies get activated when iron levels decrease, for instance as a result of treatment with iron chelators. So far, so good.

The team examined the effect of curcumin on mice whose diet also contained some iron. One group was fed more curcumin, another less, and then there was the usual control (no curcumin) group: ferritin H and L proteins were both reduced to approximately 50% of control in mice receiving 2.0% dietary curcumin. (“H” stands for heavy, “L” for light.) I would like to mention that in no case were any adverse effects or toxicity observed as a result of the administration of curcumin to the mice.

The team also found that curcumin induced ferritin mRNA but reduced ferritin protein in cultured liver cells. Ehhh? I know, I know. But I found a rather simple (?) explanation (the link to this UC Berkeley study that I used in my March draft doesn’t work anymore, sorry about that!) that may help us figure out the difference between the two types of ferritin: iron accumulates in tissues in a solid, slow release form thanks to the ferritin protein. Ferritin protein manages iron and oxygen.

Ferritin mRNA instead has to do with genes, as the “mRNA” part suggests: A special structure in ferritin mRNA controls the synthesis rate of ferritin protein when iron has entered the cell. Okay, this is probably still not completely obvious to anybody without a scientific background, like yours truly. But the point is: curcumin’s ability to distinguish between the two types of ferritin—increasing the levels of the one (ferritin mRNA) but decreasing the levels of the other (ferritin protein)—suggests that it acts as an iron chelator, since iron chelators do the exact same thing.

Let’s have a look at the study results: One mechanism of action of synthetic chemopreventive agents is the induction of cytoprotective proteins. These include ferritin, a protein that functions as a cytoprotective protein by virtue of its ability to bind iron and reduce oxidative stress. And, just like chemotherapy, curcumin increases the levels of both subunits of mRNA ferritin, H (heavy) and L (light).

But, in contrast with chemo drugs, the levels of regular ferritin protein H and L declined to approximately 65% of control in cells treated with curcumin. That is quite a drop. The team demonstrated, however, that it is possible to reverse the trend, since iron depletion causes decreased levels of ferritin: If iron depletion underlies the curcumin-dependent decrease in levels of ferritin protein, then it should be possible to reverse the effect of curcumin on ferritin by repleting cells with iron. That is exactly what happened, and the researchers found that iron blocks curcumin-dependent ferritin repression.

At the end of the study we get to a very interesting bit of news. The researchers suggest that the intake of iron as a dietary supplement may bind to and interfere with the beneficial activity of curcumin. Aha! And, in fact, earlier in the study they write that iron was recently shown to attenuate the cytotoxic effects of curcumin in cultured squamous cell carcinoma. So iron renders curcumin less effective. Makes sense.

Well, after reading this study, I will not be taking an iron supplement…for now, at least. I cannot and indeed should not avoid iron completely (it’s in a lot of foods, of course), but I certainly don’t want to take anything extra that might interfere with curcumin’s anticancer activities…no way!

UPDATE, November 7 2008 post: Another study on curcumin’s function as an iron chelator was published in “Blood” last month (abstract: http://tinyurl.com/5fhhwd). The interesting part is that these Wake Forest University NC researchers wanted To test whether the chelator activity of curcumin is sufficient to induce iron deficiency in vivo, using mice whose diets contained graded concentrations of both iron and curcumin for 26 weeks. Well, after reading the full study, I have reached a couple of conclusions. But first, the study…

 

As we can read in the abstract, the researchers found that curcumin has the potential to affect systemic iron metabolism, particularly in a setting of subclinical iron deficiency. This may affect the use of curcumin in patients with marginal iron stores or those exhibiting the anemia of cancer and chronic disease.

 

Hmmm, doesn’t sound too good, eh. Well, now for the full study (grazie Sherlock!).

 

As usual, it begins with info on how curcumin has been used traditionally, how human Phase I clinical trials of curcumin have yielded good results, such as almost no toxicity, and so on. It then discusses how curcumin works—inhibition of NF-kappaB and so on. Skip, skip. Skip.

 

Then the study mentions a 2006 study, which I discussed in a previous post (see my Page on curcumin and iron). In a nutshell, liver cells treated with curcumin showed a decrease in ferritin, raising the possibility that the chelator activity of curcumin might be sufficient to induce systemic iron depletion, potentially triggering or exacerbating subclinical or clinical iron deficiency.

 

The first thing that the researchers did was put groups of mice on either high or low iron diets. Then curcumin was added to the mix, up to the equivalent of 8-12 grams a day. No toxicity from the curcumin was observed, by the way. So far, so good.

 

Results: the addition of curcumin had no effect on the hematocrit, haemoglobin, serum iron or transferrin saturation of the “high-iron” mice BUT it did have a dramatic effect on the “low-iron” mice. All the above-mentioned values declined; the higher the curcumin dose, the lower the values.

 

However, before we freak out and toss our precious bottles of curcumin into the rubbish bin, let me say that the Discussion part of the study makes a few interesting points.

 

1. Compared to other chelators used for the treatment of iron overload, curcumin has a moderate chelator activity.

 

2. Indian diets are traditionally low in bio-available iron. This is important, since Indians consume quite a bit of curcumin via the spice from which it is extracted–turmeric. So, theoretically, Indians should be an anemic population en masse with their large consumption of turmeric and low iron intake, right? Hmmm…I doubt that that is the case…

 

On the negative side, the mice with the iron-deficient diet ended up with iron deficiency anemia, including a decline in serum iron, decreased hematocrit, decreased transferrin saturation and appearance of hypochromic red blood cells. “Hypochromic” red blood cells means “paler than usual” red blood cells = anemia (Werriam Webster definition: marked by or being red blood cells with deficient haemoglobin).

 

Then we read that Curcumin also decreased iron levels in the bone marrow and spleen. And that curcumin-mediated changes in the liver were extensive: curcumin reduced liver iron, activated IRP, repressed ferritin, blablabla.

 

This sounds really scary, but hey, after all I have been on a high dose of curcumin for almost three years, and I am not anemic. Yes, my haemoglobin is on the low end of normal but is still hanging in there. I just checked, and, as far back as 2005, my Hgb has never been super high. So, without meaning to sound flippant, I say, no big deal. My serum iron, though, took a plunge in February, after our (Sherlock’s and mine) failed Biocurcumax experiment. So far, it hasn’t recovered, and for the past three set of tests has been slightly below the normal range. I will keep an eye on it.

 

At any rate, at the end of the study, the researchers make a few important points: There are two important implications of these results. First, iron chelators have been shown to exert anti-tumor effects, both through the formation of redox-active iron complexes and by iron depletion. Thus, reduction in systemic iron resulting from the use of curcumin in the setting of a low iron diet may contribute to the anti-cancer activity of curcumin. Second, curcumin may have the potential to contribute to the development of anemia in patients with marginal iron status. This may be an important consideration when curcumin is used to treat patients with marginal or depleted iron stores or those exhibiting the anemia of cancer and chronic disease.

 

So if you are healthy but trying to prevent the development of cancer and your iron levels are normal or high, don’t worry about taking curcumin. However, you have to be more cautious if you are a cancer patient with low iron levels. Problem is, if we, the low-iron myeloma folks, add an iron supplement to our daily intake, we may end up inhibiting curcumin’s anticancer activity (again, see my Page on curcumin and iron)…sigh. Catch-22.

 

My own conclusions. Driving to work this morning, I decided to wait until I get my test results in mid December before taking any action on the iron front. I will begin taking an iron supplement in December if I see that my Hgb, serum iron and ferritin levels keep dropping compared to my July tests. If I do start taking iron, though, I will wait at least 12 hours before swallowing my curcumin, so as to minimize any possible interference.

 

In yesterday’s post I forgot to mention that a couple of weeks ago I came across a bottle of curcumin (in my medicine cabinet) that turns out not to be the C3 Complex curcumin that I usually take. No idea where it came from, my parents must have brought it with them last spring. Anyway, each capsule contains about 850 mg of curcumin, which means that I have to take only 10 capsules a day, not 16 (bonus!). And each capsule has a bit of bioperine in it, which is good. So I decided, what the heck?, and began taking this new curcumin. That was about ten days before I had my blood tests. 

 

But the big decision of the past few days is that I have decided to begin taking feverfew, in its capsule form. The parthenolide content is rather low, but I hope it WILL work anyway. This weekend I am going to do some research on when and how to take it (at the same time as I take my curcumin or not?), etc.

Next tests in January. My parthenolide tests. Exciting! -)

UPDATE: after reading this post, Sherlock wrote me a private note reminding me that her Hgb is the same as it was one year ago (=before she began taking curcumin). However, get this: her serum iron and transferrin have actually gone UP since 2007. Now that is interesting. (Hmmm, my transferrin is high, incidentally…food for thought.)

The only value that has decreased in a year’s time for Sherlock is her ferritin. So, curcumin may have a different effect on different people. After all, we are not mice! ;-)

 

17 thoughts on “Curcumin and iron

  1. Rodrigo Rojas, MD.

    Hi Margaret:
    Congratulations on your blog. It is very interesting.
    I wonder if you would be so kind as to guide me where can I buy the C3 Complex. I went to the company’s website but they don’t seem to provide info as to where one can purchase the C3 from. Maybe I am missing something.
    I would appreciate your help.
    Thank you,

    Rodrigo Rojas, MD.

    Reply
  2. Diane

    Hello Dr. Rojas,

    Margaret takes Curcumin C3 with Piperine in 500mg w/o silicone as discussed in her 2007/2008 blog entry: margaret.healthblogs.org/life-with-myeloma/what-is-curcumin/curcumin-brandssources-in-the-us-and-europe-powder-and-capsules/

    One source is: http://www.vitacost.com/Doctors-Best-Curcumin-C3-Complex

    Vitacost has its own brand of Curcumin C3 with Piperine in 500mg w/o silicone, but it does not appear on the web site today.

    I purchase mine at this site: www26.netrition.com/doctors_best_curcumin_c3.html

    Diane

    Reply
  3. Mike

    Margaret

    Where do you speak about silicon dioxide being bad in supplements? Can’t find it. What does it do? I see alot of things added in to supplements. I try to get the least amount added even if it costs a little more.

    Reply
  4. William

    I just started taking the Vitamin Shoppe brand of Curcumin. Each capsule is 900 mg of Tumeric Extract with 5mg of Bioperine. I am now taking a total of 6 a day, 3 when I wake, 3 in the afternoon. Has anyone else tried this brand. It is the store brand, and they have a good rep for vitamins/minerals/health supplememts, along with bodybuilding supplies. I looked at the Vitacost site, and after reading some reviews about their billing, was hesitant. Any info would be appreciated. Thanks, William.

    Reply
  5. Gloria

    Well I am mexican and its hard to understand completely all info, so if a person has anemya shouldn´t take curcumine? or maybe you can get eritropoyetina instead taking iron so you can take curcumine? thank you so much!

    Reply
  6. Diane A.

    Gloria – Your doctor is able to test for your blood levels of iron. Then the doctor will prescribe iron IF you need it, based upon your test results. Ask your doctor at your next visit?

    Reply
  7. Gloria

    Thanks for your comments!! I just have a question, dear Margaret I was reading at the MM facebook group that you take eight capsules by day of C3 complex in order to take 8grams, I haven`t realized that every capsule is 500 mg so you need to take eight to complete 8gr, is that right? do you take all the capsules at the same time or with meals? Thank you so much!

    Reply
  8. Richie

    I have just recently been diagnosed with SM and immediately began taking Curcumin as part of my preventive plan. My hematologist was the typical type hesitant to try alternative methods (no shocker there). I let him know I was going to try it and he didn’t seem to feel it would hurt me. I started a week ago and since I’m feeling a little lethargic and am now wondering if its the Iron chelation? I feel like now I’m between a rock and a hard place with this and just wondering if you ever started taking the iron supplements and what were your results?

    Reply
  9. Andrea

    My iron levels were always on the low side of normal, and dropped even more when I began taking the curcumin. I remedied this situation (after reading the advice put forth by ‘The Iron Council”)and changed the time I take the curcumin. I now leave a two hour window before and after I eat in order to alow the nutrients from my food to be absorbed. Many substances block iron absorption, and curcumin is one of them.

    Reply
  10. Diane

    Andrea, (posted 3-28-13) How has the timing of your curcumin worked in relation to your iron supplementation and bloodwork? I would like to begin curcumin, but I am cautious due to my Hgb level. (11.5 when normal is 12)

    Reply
  11. Andrea

    Diane-Seems to be working this way. I have been taking 8g of curcumin for over a year now. My iron levels have increased a little, currently up to 11.8 (from 11.4)which is good for me. I was never at 12, even before my SMM. I also feel fine. I am seeing a naturapath who explained that for some people the low range, if holding steady, can be normal. Especially if you feel well (not tired or having palpatations). Hope this helps.

    Reply
  12. Janet

    Interesting reading! I just had blood tests done after losing 15 lbs out of the blue (I would like to just enjoy that, but its totally out of character for me!). Anyways, my blood test came back with very low iron… I have always been borderline anyways, but doing some research into the use of curcumin and anemia led me to here. Thanks for the interesting read!

    Reply
  13. Beth

    Ah ha! I don’t know why i didn’t read this sooner. I’ve had absent iron stores ever since I was diagnosed with MM (and most certainly before that). My doctor has been wanting me to supplement with iron, since my TSAT is always low. Right now, it’s at 12% (15 is the low normal), but has been as low as 9 in recent months. I didn’t realize that taking iron supplements could counteract the desired effects of the curc. I’m less interested in my iron stores than I am in keeping the MM stable. But, I do experience some of the symptoms that come with iron deficiency anemia. The question is, what to do? Margaret, what’s your TSAT value? What about iron binding?

    Reply
  14. Pat

    Chili, but not turmeric, inhibits iron absorption in young women from an iron-fortified composite meal.
    Tuntipopipat S, Judprasong K, Zeder C, Wasantwisut E, Winichagoon P, Charoenkiatkul S, Hurrell R, Walczyk T.
    Author information
    Abstract

    Chili and turmeric are common spices in indigenous diets in tropical regions. Being rich in phenolic compounds, they would be expected to bind iron (Fe)(3) in the intestine and inhibit Fe absorption in humans. Three experiments were conducted in healthy young women (n = 10/study) to assess the effect of chili and turmeric on Fe absorption from a rice-based meal containing vegetables and iron fortified fish sauce in vivo. Iron absorption was determined by erythrocyte incorporation of stable isotope labels ((57)Fe/(58)Fe) using a randomized crossover design. Addition of freeze-dried chili (4.2 g dry powder, 25 mg polyphenols as gallic acid equivalents) reduced Fe absorption from the meal by 38% (6.0% with chili vs. 9.7% without chili, P = 0.0017). Turmeric (0.5 g dry powder, 50 mg polyphenols as gallic acid equivalents) did not inhibit iron absorption (P = 0.91). A possible effect of chili on gastric acid secretion was indirectly assessed by comparing Fe absorption from acid soluble [(57)Fe]-ferric pyrophosphate relative to water soluble [(58)Fe]-ferrous sulfate from the same meal in the presence and absence of chili. Chili did not enhance gastric acid secretion. Relative Fe bioavailability of ferric pyrophosphate was 5.4% in presence of chili and 6.4% in absence of chili (P = 0.47). Despite the much higher amount of phenolics in the turmeric meal, it did not affect iron absorption. We conclude that both phenol quality and quantity determine the inhibitory effect of phenolic compounds on iron absorption.

    Reply
  15. shirley

    Hi There, My husband has what is called Hemochromatosis. It is a blood disorder. It is inheritited. It is basically iron load. His body absorbs too much iron. Do you know anything about this condition. My husband is interested in taking this product, but we are confused. It does have iron in it and and vitiam c. Our kids, grandkids have to also be watched for this. The normal range for ferritin should be well under 500 and His was 1700. He was a big red meat eater.The Dr. said Only red meat 2 times a week and small amounts. Also read lables. Have you heard of this condition? Every 2 weeks since last may he has to go in a they take a bag of blood from him to help get his levels down.

    Reply

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