Scientific and Clinical Research on Nutritional Supplementation and Iron Overload

Clinical Research for Green Tea and Hemochromatosis:
  • Srichairatanakool S, Ounjaijean S, Thephinlap C, Khansuwan U, Phisalpong C, Fucharoen S. Iron-chelating and free-radical scavenging activities of microwave-processed green tea in iron overload. Hemoglobin. 2006;30(2):311-327.
  • Mandel S, Amit T, Reznichenko L, Weinreb O, Youdim MBH. Green tea catechins as brain-permeable, natural iron chelators-antioxidants for the treatment of neurodegenerative disorders. Mol. Nutr. Food Res. 2006;50(2):229-234.
  • Imai K and Nakachi K. Cross sectional study of effects of drinking green tea on cardiovascular and liver diseases.BMJ. 1995;310(6981):693-696.
  • Samman S, Sandström B, Toft MB, et al. Green tea or rosemary extract added to foods reduces nonheme-iron absorption. Am J ClinNutr. 2001;73(3):607-612.
  • Ounjaijean S(1), Thephinlap C, Khansuwan U, Phisalapong C, Fucharoen S, Porter JB, Srichairatanakool S. Effect of Green Tea on Iron Status and Oxidative Stress in Iron-loaded Rats. Med Chem. 2008 Jul;4(4):365-70.
  • Thephinlap C, Ounjaijean S, Khansuwan U, Fucharoen S, Porter JB, Srichairatanakool S. Epigallocatechin-3-gallate and epicatechin-3-gallate from green tea decrease plasma non-transferrin bound iron and erythrocyte oxidative stress. Med Chem. 2007 May;3(3):289-96. PubMed PMID: 17504202.
  • Saewong T, Ounjaijean S, Mundee Y, Pattanapanyasat K, Fucharoen S, Porter JB, Srichairatanakool S. Effects of green tea on iron accumulation and oxidative stress in livers of iron-challenged thalassemic mice. Med Chem. 2010 Mar;6(2):57-64. PubMed PMID: 20218965.
  • Mandel SA, Avramovich-Tirosh Y, Reznichenko L, Zheng H, Weinreb O, Amit T, Youdim MB. Multifunctional activities of green tea catechins in neuroprotection. Modulation of cell survival genes, iron-dependent oxidative stress and PKC signaling pathway. Neurosignals. 2005;14(1-2):46-60. Review. PubMed PMID: 15956814.
  • Claudine Manach, Augustin Scalbert, Christine Morand, Christian Rémésy, and Liliana Jiménez. Polyphenols: food sources and bioavailability. Am J Clin Nutr May 2004 vol. 79 no. 5 727-747.
Clinical Research for Milk Thistle and Hemochromatosis:
  • Abenavoli L, Capasso R, Milic N, Capasso F. Milk Thistle in Liver Diseases: Past, Present, Future. Phytother Res. 2010 Oct;24(10):1423-32. doi: 10.1002/ptr.3207. PMID: 20564545
  • Bares JM, Berger J, Nelson JE, et al. Silybin treatment is associated with reduction in serum ferritin in patients with chronic hepatitis C. J. Clin. Gastroenterol. 2008;42(8):937-944.
  • Gharagozloo M, Moayedi B, Zakerinia M, et al. Combined therapy of silymarin and desferrioxamine in patients with beta-thalassemia major: a randomized double-blind clinical trial. FundamClinPharmacol. 2009;23(3):359-365.
  • Hutchinson C, Bomford A, Geissler CA. The Iron-Chelating Potential of Silybin in Patients with Hereditary Haemochromatosis. Eur J Clin Nutr. 2010 Oct;64(10):1239-41. doi: 10.1038/ejcn.2010.136. Epub 2010 Jul 14. PMID: 20628405
  • Bell, Warren. What’s in a Name? Can Fam Physician. 2008 Feb; 54(2): 183–185. PMCID: PMC2278302
  • Kidd R. Exacerbation of Hemochromatosis by Ingestion of Milk Thistle. Can Fam Physician. 2008 Feb;54(2):182; author reply 182-3. PMID: 18272626
  • Whittington C. Exacerbation of hemochromatosis by ingestion of milk thistle. Can Fam Physician. 2007;53:1671–3. PMID: 17934030
Clinical Research for Taurine and Hemochromatosis:
  • Zhang Z, Liu D, Yi B, Liao Z, Tang L, Yin D, He M. Taurine supplementation reduces oxidative stress and protects the liver in an iron-overload murine model. Mol Med Rep. 2014 Nov;10(5):2255-62. doi: 10.3892/mmr.2014.2544. Epub 2014 Sep 5. PubMed PMID: 25201602; PubMed Central PMCID: PMC4199407.
  • Lawless MW, Mankan AK, White M, O'Dwyer MJ, Norris S. Expression of hereditary hemochromatosis C282Y HFE protein in HEK293 cells activates specific endoplasmicreticulum stress responses. BMC Cell Biol. 2007 Jul 24;8:30. PubMed PMID: 17650303; PubMed Central PMCID: PMC1947972.
  • Oudit GY, Trivieri MG, Khaper N, Husain T, Wilson GJ, Liu P, Sole MJ, Backx PH. Taurine supplementation reduces oxidative stress and improves cardiovascular function in an iron-overload murine model. Circulation. 2004 Apr 20;109(15):1877-85. Epub 2004 Mar 22. PubMed PMID: 15037530.
  • Dawson R Jr, Baker D, Eppler B, Tang E, Shih D, Hern H, Hu M. Taurine inhibition of metal-stimulated catecholamine oxidation. Neurotox Res. 2000;2(1):1-15. PubMed PMID: 15545001.
  • Messina SA, Dawson R Jr. Attenuation of oxidative damage to DNA by taurine and taurine analogs. Adv Exp Med Biol. 2000;483:355-67. PubMed PMID: 11787620.
  • Lawless MW, Mankan AK, Ryan AW, Norris S. Tauroursodeoxycholic acid: relieving the pathogenesis of HFE C282Y hereditary hemochromatosis. Hepatology. 2008Jul;48(1):344-5. doi: 10.1002/hep.22155. PubMed PMID: 18203149.
  • de Almeida SF, Picarote G, Fleming JV, Carmo-Fonseca M, Azevedo JE, de Sousa M. Chemical chaperones reduce endoplasmic reticulum stress and prevent mutant HFE aggregate formation. J Biol Chem. 2007 Sep 21;282(38):27905-12. Epub 2007 Jul 11. PubMed PMID: 17626021.
  • Devi SL, Viswanathan P, Anuradha CV. Regression of liver fibrosis by taurine in rats fed alcohol: effects on collagen accumulation, selected cytokines and stellate cell activation. Eur J Pharmacol. 2010 Nov 25;647(1-3):161-70. doi: 10.1016/j.ejphar.2010.08.011. Epub 2010 Sep 4. PubMed PMID: 20813107.
  • Devi SL, Anuradha CV. Oxidative and nitrosative stress in experimental rat liver fibrosis: Protective effect of taurine. Environ Toxicol Pharmacol. 2010 Mar;29(2):104-10. doi: 10.1016/j.etap.2009.11.005. Epub 2009 Nov 24. PubMed PMID: 21787590.
  • Manna P, Sinha M, Sil PC. Amelioration of cadmium-induced cardiac impairment by taurine. Chem Biol Interact. 2008 Jul 30;174(2):88-97. doi: 10.1016/j.cbi.2008.05.005. Epub 2008 May 15. PubMed PMID: 18561905.
  • Eppler B, Dawson R Jr. Cytoprotective role of taurine in a renal epithelial cell culture model. Biochem Pharmacol. 2002 Mar 15;63(6):1051-60. PubMed PMID: 11931837.
  • Dawson R Jr, Tang E, Shih D, Hern H, Hu M, Baker D, Eppler B. Taurine inhibition of iron-stimulated catecholamine oxidation. Adv Exp Med Biol. 1998;442:155-62. PubMed PMID: 9635027.
  • Hua HM, Ito T, Qiu ZG, Azuma J. [Progress in research on function and mechanism of cardiac vascular system of taurine]. Zhongguo Zhong Yao Za Zhi. 2005May;30(9):653-8. Review. Chinese. PubMed PMID: 16075725.
Clinical Research for Alpha Lipoic Acid and Hemochromatosis:
  • Suh JH, Moreau R, Heath, SH, Hagen TM. Dietary supplementation with (R)-alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Redox Rep. 2005;10(1):52-60.
  • Lovell MA, Xie C, Xiong S, Markesbery WR. Protection against amyloid beta peptide and iron/hydrogen peroxide toxicity by alpha lipoic acid. J. Alzheimers Dis. 2003;5(3):229-239.
Clinical Research for Calcium and Iron Absorption:
  • Hallberg L, Rossander-Hultén L, Brune M, Gleerup A. Calcium and iron absorption: mechanism of action and nutritional importance. Eur J Clin Nutr. 1992. May;46(5):317-27. Cook JD, Dassenko SA, Whittaker P. Calcium supplementation: effect on iron absorption. Am J Clin Nutr. 1991 Jan;53(1):106-11.
  • Hallberg L, Brune M, Erlandsson M, Sandberg AS, Rossander-Hultén L. Calcium:
  • effect of different amounts on nonheme- and heme-iron absorption in humans. Am J Clin Nutr. 1991 Jan;53(1):112-9.
  • Minihane AM, Fairweather-Tait SJ. Effect of calcium supplementation on daily nonheme-iron absorption and long-term iron status. Am J Clin Nutr. 1998. Jul;68(1):96-102.
  • Harris SS. The effect of calcium consumption on iron absorption and iron status. Nutr Clin Care. 2002 Sep-Oct;5(5):231-5.
  • Bendich A. Calcium supplementation and iron status of females. Nutrition. 2001. Jan;17(1):46-51.
  • Benkhedda K, L'abbé MR, Cockell KA. Effect of calcium on iron absorption in women with marginal iron status. Br J Nutr. 2010 Mar;103(5):742-8.
  • Hurrell R, Egli I. Iron bioavailability and dietary reference values. Am J Clin Nutr. 2010 May;91(5):1461S-1467S.
  • Lönnerdal B. Calcium and iron absorption--mechanisms and public health relevance. Int J Vitam Nutr Res. 2010 Oct;80(4-5):293-9.
  • Lynch SR. The effect of calcium on iron absorption. Nutr Res Rev. 2000. Dec;13(2):141-58
    Clinical Research for Magnesium and Iron Absorption:
    • Disch G, Classen HG, Haubold W, Spätling L. Interactions between magnesium and iron. In vitro studies. Arzneimittelforschung. 1994 May;44(5):647-50. PubMed PMID: 8024640.
    • Snyder BK, Clark RF. Effect of magnesium hydroxide administration on iron absorption after a supratherapeutic dose of ferrous sulfate in human volunteers: a randomized controlled trial. Ann Emerg Med. 1999 Apr;33(4):400-5. PubMed PMID: 10092717.
    • Wallace KL, Curry SC, LoVecchio F, Raschke RA. Effect of magnesium hydroxide on iron absorption following simulated mild iron overdose in human subjects. Acad Emerg Med. 1998 Oct;5(10):961-5. PubMed PMID: 862585.
      Clinical Research for Turmeric (“Curcumin”) and Iron:
      • Srichairatanakool, S., Thephinlap, C., Phisalaphong, C., Porter, J. B., and Fucharoen, S. Curcumin contributes to in vitro removal of non-transferrin bound iron by deferiprone and desferrioxamine in thalassemic plasma. Med.Chem. 2007;3(5):469-474.
      • Jiao, Y., Wilkinson, J., Christine, Pietsch E., Buss, J. L., Wang, W., Planalp, R., Torti, F. M., and Torti, S. V. Iron chelation in the biological activity of curcumin. Free Radic.Biol.Med. 4-1-2006;40(7):1152-1160.
      • Jiao, Y., Wilkinson, J., Di, X., Wang, W., Hatcher, H., Kock, N. D., D’Agostino, R., Jr., Knovich, M. A., Torti, F. M., and Torti, S. V. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. Blood 1-8-2009;113(2):462-469.
      • Tuntipopipat, S., Zeder, C., Siriprapa, P., and Charoenkiatkul, S. Inhibitory effects of spices and herbs on iron availability. Int.J Food Sci.Nutr. 2009;60 Suppl 1:43-55.
      • Tuntipopipat, S., Judprasong, K., Zeder, C., Wasantwisut, E., Winichagoon, P., Charoenkiatkul, S., Hurrell, R., and Walczyk, T. Chili, but not turmeric, inhibits iron absorption in young women from an iron-fortified composite meal. J Nutr. 2006;136(12):2970-2974.
      • Baum, L. and Ng, A. Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimers.Dis. 2004;6(4):367-377.
      • Ishihara, M. and Sakagami, H. Re-evaluation of cytotoxicity and iron chelation activity of three beta-diketones by semiempirical molecular orbital method. In Vivo 2005;19(1):119-123.
      • Bernabe-Pineda, M., Ramirez-Silva, M. T., Romero-Romo, M. A., Gonzalez-Vergara, E., and Rojas-Hernandez, A. Spectrophotometric and electrochemical determination of the formation constants of the complexes Curcumin-Fe(III)-water and Curcumin-Fe(II)-water. Spectrochim.Acta A Mol.Biomol.Spectrosc. 2004;60(5):1105-1113.
      • Reddy, A. C. and Lokesh, B. R. Effect of dietary turmeric (Curcuma longa) on iron-induced lipid peroxidation in the rat liver. Food Chem.Toxicol 1994;32(3):279-283.
      • Reddy, A. C. and Lokesh, B. R. Studies on the inhibitory effects of curcumin and eugenol on the formation of reactive oxygen species and the oxidation of ferrous iron. Mol.Cell Biochem. 8-17-1994;137(1):1-8.
      • Reddy, A. C. and Lokesh, B. R. Effect of curcumin and eugenol on iron-induced hepatic toxicity in rats. Toxicology 1-22-1996;107(1):39-45.
      • Mandel, S., Amit, T., Bar-Am, O., and Youdim, M. B. Iron dysregulation in Alzheimer’s disease: multimodal brain permeable iron chelating drugs, possessing neuroprotective-neurorescue and amyloid precursor protein-processing regulatory activities as therapeutic agents. Prog.Neurobiol. 2007;82(6):348-360.
      • Jyoti, A., Sethi, P., and Sharma, D. Curcumin protects against electrobehavioral progression of seizures in the iron-induced experimental model of epileptogenesis. Epilepsy Behav. 2009;14(2):300-308.
      • Thephinlap, C., Phisalaphong, C., Lailerd, N., Chattipakorn, N., Winichagoon, P., Vadolus, J., Fucharoen, S., Porter, J. B., and Srichairatanakool, S. Reversal of cardiac iron loading and dysfunction in thalassemic mice by curcuminoids. Med Chem 2011;7(1):62-69.
      • Thephinlap C, Phisalaphong C, Fucharoen S, Porter JB, Srichairatanakool S.Efficacy of curcuminoids in alleviation of iron overload and lipid peroxidation in thalassemic mice. Med Chem. 2009 Sep;5(5):474-82.

      Topical Application of Turmeric Studies:

      • Hegge AB1, Schüller RB, Kristensen S, Tønnesen HH. In vitro release of curcumin from vehicles containing alginate and cyclodextrin. Studies of curcumin and curcuminoides. XXXIII. Pharmazie. 2008 Aug;63(8):585-92.
      • Teichmann A1, Heuschkel S, Jacobi U, Presse G, Neubert RH, Sterry W, Lademann J. Comparison of stratum corneum penetration and localization of a lipophilic model drug applied in an o/w microemulsion and an amphiphilic cream. Eur J Pharm Biopharm. 2007 Nov;67(3):699-706.
      • (**Note: In respect to the above study, our Turmeric Cream is a “microemulsion” preparation and not a “amphiphillic” preparation)
      • Fang JY1, Hung CF, Chiu HC, Wang JJ, Chan TF. Efficacy and irritancy of enhancers on the in-vitro and in-vivo percutaneous absorption of curcumin. J Pharm Pharmacol. 2003 May;55(5):593-601.
      • Fang JY1, Hung CF, Chiu HC, Wang JJ, Chan TF. Efficacy and irritancy of enhancers on the in-vitro and in-vivo percutaneous absorption of curcumin. J Pharm Pharmacol. 2003 Aug;55(8):1175.
      • Patel NA1, Patel NJ, Patel RP. Design and evaluation of transdermal drug delivery system for curcumin as an anti-inflammatory drug. Drug Dev Ind Pharm. 2009 Feb;35(2):234-42.
      • H Moghimi, B Shahmir, A Zarghi. Enhancement of percutaneous absorption of curcumin (turmeric pigment) by ethanol. IJPR. Iranian Journal of Pharmaceutical Research. Article 21, Volume 3, Supplement 2, Autumn 2004, Pages 8-9.
      • (**Note: In respect to the above study, our Turmeric Cream contains alcohol as an ingredient to enhance absorption)

      Clinical Research for Vitamin E and Iron Absorption:

      • Young, Ian S., Tom G. Trouton, Jonathan J. Torney, Dorothy McMaster, Michael E. Callender, and Elisabeth R. Trimble. "Antioxidant status and lipid peroxidation in hereditary haemochromatosis." Free Radical Biology and Medicine 16, no. 3 (1994): 393-397.
      • von Herbay, Alexandra, Herbert de Groot, Udo Hegi, Wolfgang Stremmel, Georg Strohmeyer, and Helmut Sies. "Low vitamin E content in plasma of patients with alcoholic liver disease, hemochromatosis and Wilson's disease." Journal of Hepatology 20, no. 1 (1994): 41-46.
      • Brown, Kyle E., John E. Poulos, L. Li, Assaad M. Soweid, Grant A. Ramm, Rosemary. O'neill, Robert S. Britton, and Bruce R. Bacon. "Effect of vitamin E supplementation on hepatic fibrogenesis in chronic dietary iron overload." American Journal of Physiology-Gastrointestinal and Liver Physiology 272, no. 1 (1997): G116-G123.
      • McCullough, Karey D., and Wally J. Bartfay. "The dose-dependent effects of chronic iron overload on the production of oxygen free radicals and vitamin E concentrations in the liver of a murine model." Biological Research for Nursing 8, no. 4 (2007): 300-304.