Curcumin & Iron

Some have heard about Curcumin's iron chelation properties and it has caused some concern, understandably. So, I went ahead and researched it out further.

I did ask Blake about it and then I went ahead and researched it out for myself. My findings are consistent with what I have heard from others.

From what I have researched, Curcumin appears to act as an iron chelator. It actually seems to be part of the benefits of Curcumin and one of the ways it is a powerful antioxidant. Here is a quote from the full text of one of the abstracts I will post below (listed with a couple ** by it):

“Iron chelators could be important as chemopreventive agents, and have mechanisms of action consistent with that role. Iron chelators prevent the participation of iron in the Fenton reaction, which reductively cleaves hydrogen peroxide to produce the hydroxyl radical. By inhibiting this and other iron-catalyzed pathways of oxidative stress [45], iron chelators substantially reduce oxidative injury to critical cellular targets, including DNA, lipids, and protein [46,47]. Such an ability to protect against oxidative stress is a hallmark of a chemopreventive agent [48].”

The iron chelation properties of Curcumin do not seem to be much of a concern though. It should be watched if a person is prone to low levels of iron already or anemic to begin with. But, technically it should not be a problem. If there are excessive levels of iron it may chelate some of them, but it doesn’t automatically take away all iron in the body.

----Some abstracts covering this topic:

Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator.

Jiao Y, Wilkinson J 4th, Di X, Wang W, Hatcher H, Kock ND, D'Agostino R Jr, Knovich MA, Torti FM, Torti SV.

Curcumin is a natural product currently in human clinical trials for a variety of neoplastic, preneoplastic, and inflammatory conditions. We previously observed that, in cultured cells, curcumin exhibits properties of an iron chelator. To test whether the chelator activity of curcumin is sufficient to induce iron deficiency in vivo, mice were placed on diets containing graded concentrations of both iron and curcumin for 26 weeks. Mice receiving the lowest level of dietary iron exhibited borderline iron deficiency, with reductions in spleen and liver iron, but little effect on hemoglobin, hematocrit, transferrin saturation, or plasma iron. Against this backdrop of subclinical iron deficiency, curcumin exerted profound 2 effects on systemic iron, inducing a dose-dependent decline in hematocrit, hemoglobin, serum iron, and transferrin saturation, the appearance of microcytic anisocytotic red blood cells, and decreases in spleen and liver iron content. Curcumin repressed synthesis of hepcidin, a peptide that plays a central role in regulation of systemic iron balance. These results demonstrate 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.

**Iron chelation in the biological activity of curcumin.** **Click here for full text**

Jiao Y, Wilkinson J 4th, Christine Pietsch E, Buss JL, Wang W, Planalp R, Torti FM, Torti SV.
Department of Cancer Biology, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.

Curcumin is among the more successful chemopreventive compounds investigated in recent years, and is currently in human trials to prevent cancer. The mechanism of action of curcumin is complex and likely multifactorial. We have made the unexpected observation that curcumin strikingly modulates proteins of iron metabolism in cells and in tissues, suggesting that curcumin has properties of an iron chelator. Curcumin increased mRNA levels of ferritin and GSTalpha in cultured liver cells. Unexpectedly, however, although levels of GSTalpha protein increased in parallel with mRNA levels in response to curcumin, levels of ferritin protein declined. Since iron chelators repress ferritin translation, we considered that curcumin may act as an iron chelator. To test this hypothesis, we measured the effect of curcumin on transferrin receptor 1, a protein stabilized under conditions of iron limitation, as well as the ability of curcumin to activate iron regulatory proteins (IRPs). Both transferrin receptor 1 and activated IRP, indicators of iron depletion, increased in response to curcumin. Consistent with the hypothesis that curcumin acts as an iron chelator, mice that were fed diets supplemented with curcumin exhibited a decline in levels of ferritin protein in the liver. These results suggest that iron chelation may be an additional mode of action of curcumin.

Curcumin: From ancient medicine to current clinical trials

H. Hatcher1, R. Planalp2, J. Cho2, F. M. Torti1, 4 and S. V. Torti3, 4

Abstract. Curcumin is the active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa). Curcumin has a surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. The pleiotropic activities of curcumin derive from its complex chemistry as well as its ability to influence multiple signaling pathways, including survival pathways such as those regulated by NF-κB, Akt, and growth factors; cytoprotective pathways dependent on Nrf2; and metastatic and angiogenic pathways. Curcumin is a free radical scavenger and hydrogen donor, and exhibits both pro- and antioxidant activity. It also binds metals, particularly iron and copper, and can function as an iron chelator. Curcumin is remarkably non-toxic and exhibits limited bioavailability. Curcumin exhibits great promise as a therapeutic agent, and is currently in human clinical trials for a variety of conditions, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis and Alzheimer’s disease.
A theoretical study on Cu(II)-chelating properties of curcumin and its implications for curcumin as a multipotent agent to combat Alzheimer's disease. Curcumin has been recognized as an efficient natural product to treat Alzheimer's disease (AD) by scavenging radicals and blocking Aβ aggregation. As metal ions, e.g. Cu(II), are also implicated in AD and curcumin is a metal chelator, it is interesting to investigate curcumin's metal-chelating property, which stimulates our interest to evaluate curcumin's Cu(II)-chelating ability and the effect of Cu(II) on its radical-scavenging activity by theoretical calculation. It was revealed that curcumin could efficiently sequester Cu(II) and the Cu(II)-curcumin complexes were more active than the parent curcumin in scavenging radicals by donating proton or electron. Therefore, curcumin is a multipotent agent to combat AD, with the activities of scavenging ROS, blocking Aβ aggregation and chelating metal ions.

Efficacy of curcuminoids in alleviation of iron overload and lipid peroxidation in thalassemic mice.

Thephinlap C, Phisalaphong C, Fucharoen S, Porter JB, Srichairatanakool S.
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

Non-transferrin bound iron (NTBI) is detectable in plasma of beta-thalassemia patients and participates in free-radical formation and oxidative tissue damage. Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are iron chelators used for treatment of iron overload; however they may cause adverse effects. Curcuminoids (CUR) exhibits many pharmacological activities and presents beta-diketone group to bind metal ions. Iron-chelating capacity of CUR was investigated in thalassemic mice. The mice (C57BL/6 stain); wild type ((mu)beta(+/+)) and heterozygous beta-knockout ((mu)beta(th-3/+)) were fed with ferrocene-supplemented diet for 2 months, and coincidently intervened with CUR (200 mg/kg/day) and DFP (50 mg/kg/day). Plasma NTBI was quantified using NTA chelation/HPLC method, and MDA concentration was analyzed by TBARS-based HPLC. Hepatic iron content (HIC) and total glutathione concentration were measured colorimetrically. Tissue iron accumulation was determined by Perl's staining. Ferrocene-supplemented diet induced occurrence of NTBI in plasma of thalassemic mice as well as markedly increased iron deposition in spleen and liver. Treatment with CUR and DFP decreased levels of the NTBI and MDA effectively. Hepatic MDA and nonheme iron content was also decreased in liver of the treated mice whilst total glutathione levels were increased. Importantly, the CUR and DFP reduced liver weight index and iron accumulation. Clearly, CUR is effective in chelation of plasma NTBI in iron-loaded thalassemic mice. Consequently, it can alleviate iron toxicity and harmfulness of free radicals. In prospective, efficacy of curcumin in removal of labile iron pool (LIP) in hepatocytes and cardiomyocytes are essential for investigation.

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Another plus for Curcumin: Hydrogen peroxide scavenger ~

Antioxidant and radical scavenging properties of curcumin.

Ak T, Gülçin I.
Faculty of Arts and Sciences, Department of Chemistry, Atatürk University, TR-25240 Erzurum, Turkey.

Curcumin (diferuoyl methane) is a phenolic compound and a major component of Curcuma longa L. In the present paper, we determined the antioxidant activity of curcumin by employing various in vitro antioxidant assays such as 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH*) scavenging, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, N,N-dimethyl-p-phenylenediamine dihydrochloride (DMPD) radical scavenging activity, total antioxidant activity determination by ferric thiocyanate, total reducing ability determination by the Fe(3+)-Fe(2+) transformation method, superoxide anion radical scavenging by the riboflavin/methionine/illuminate system, hydrogen peroxide scavenging and ferrous ions (Fe(2+)) chelating activities. Curcumin inhibited 97.3% lipid peroxidation of linoleic acid emulsion at 15 microg/mL concentration (20 mM). On the other hand, butylated hydroxyanisole (BHA, 123 mM), butylated hydroxytoluene (BHT, 102 mM), alpha-tocopherol (51 mM) and trolox (90 mM) as standard antioxidants indicated inhibition of 95.4, 99.7, 84.6 and 95.6% on peroxidation of linoleic acid emulsion at 45 microg/mL concentration, respectively. In addition, curcumin had an effective DPPH* scavenging, ABTS*(+) scavenging, DMPD*(+) scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, ferric ions (Fe(3+)) reducing power and ferrous ions (Fe(2+)) chelating activities. Also, BHA, BHT, alpha-tocopherol and trolox, were used as the reference antioxidant and radical scavenger compounds. According to the present study, curcumin can be used in the pharmacological and food industry because of these properties.

Qadoshyah