American Journal of Food and Nutrition
ISSN (Print): 2374-1155 ISSN (Online): 2374-1163 Website: https://www.sciepub.com/journal/ajfn Editor-in-chief: Mihalis Panagiotidis
Open Access
Journal Browser
Go
American Journal of Food and Nutrition. 2021, 9(3), 122-131
DOI: 10.12691/ajfn-9-3-5
Open AccessArticle

Nutritional Yeast Ferritin-Iron Complex: A Novel Source of Dietary Iron

James R. Connor1, , Erica L. Unger2, Ralph L. Keil3, John Flanagan3, Stephanie M. Patton1, Gabriele R Lubach4, Martin M. Schafer5 and Christopher L Coe4

1Department of Neurosurgery, Pennsylvania State University, Pennsylvania State University College of Medicine, Hershey, PA

2Department of Biology, Lebanon Valley College, Annville, PA

3Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA

4Harlow Center, University of Wisconsin, Madison WI

5Wisconsin State Laboratory of Hygiene, University of Wisconsin, Madison, WI

Pub. Date: November 23, 2021

Cite this paper:
James R. Connor, Erica L. Unger, Ralph L. Keil, John Flanagan, Stephanie M. Patton, Gabriele R Lubach, Martin M. Schafer and Christopher L Coe. Nutritional Yeast Ferritin-Iron Complex: A Novel Source of Dietary Iron. American Journal of Food and Nutrition. 2021; 9(3):122-131. doi: 10.12691/ajfn-9-3-5

Abstract

Iron deficiency anemia (IDA) is the leading nutritional disorder in the world. Iron deficiency (ID) occurs commonly in the US, particularly among children and women and in the elderly. Its impact on quality of life includes decreased cognitive ability and increased fatigue. Thus, there is clearly a need for effective and economical approaches to providing adequate dietary iron. We introduce nutritional yeast (S. cerevisiae) technologically modified to express human H-ferritin as a potential source of dietary iron. The efficacy of the yeast ferritin complex (YFC) was tested in established rat and monkey models of ID. In the rat model of ID, YFC improved hemoglobin (Hgb), hematocrit (Hct) levels as well as plasma iron and transferrin saturation and liver and spleen iron concentrations. Moreover, the YFC achieved a larger effect on Hgb and Hct with consumption of less iron compared to ferrous sulfate over a similar period. In the monkeys, YFC supplemented diet significantly improved Hgb levels within one month and increased mean corpuscular volume (MCV) by two months. To demonstrate that the Fe in the YFC was utilized by RBCs, we used a labeled isotope approach and found Fe from the ferritin in the monkeys’ RBCs with 5 days of consumption. This is the first attempt to use H-ferritin homopolymer as a nutritional iron source. Previous data from our laboratory and others have established H-ferritin as a significant iron delivery protein to the brain. Thus, H-ferritin appears to have a novel function as an iron delivery protein independent from its cooperation with L-ferritin to form an iron storage protein.

Keywords:
iron deficiency nutritional yeast ferritin iron

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Figures

Figure of 8

References:

[1]  Stoltzfus, R.J., Iron deficiency: global prevalence and consequences. Food Nutr Bull, 2003. 24(4 Suppl): p. S99-103.
 
[2]  Shafir, T., et al., Iron deficiency anemia in infancy and reach and grasp development. Infant Behav Dev, 2009. 32(4): p. 366-75.
 
[3]  Lozoff, B., et al., Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Pediatrics, 2000. 105(4): p. E51.
 
[4]  Lozoff, B., Iron Deficiency and Child Development. Food and Nutrition Bulletin, 2007. 28(4_suppl4): p. S560-S571.
 
[5]  Lukowski, A.F., et al., Iron deficiency in infancy and neurocognitive functioning at 19 years: evidence of long-term deficits in executive function and recognition memory. Nutr Neurosci, 2010. 13(2): p. 54-70.
 
[6]  Peirano, P.D., et al., Sleep and neurofunctions throughout child development: lasting effects of early iron deficiency. J Pediatr Gastroenterol Nutr, 2009. 48 Suppl 1(0 1): p. S8-15.
 
[7]  Unger, E.L., et al., Early Iron Deficiency Alters Sensorimotor Development and Brain Monoamines in Rats. The Journal of Nutrition, 2007. 137(1): p. 118-124.
 
[8]  Connor, J.R., et al., Manipulation of brain iron status in two mutant mouse models: effects on myelin. Journal of Neurochemistry, 2002. 81(s1): p. 49-51.
 
[9]  Tran, P.V., et al., Early-life iron deficiency anemia alters neurotrophic factor expression and hippocampal neuron differentiation in male rats. J Nutr, 2008. 138(12): p. 2495-501.
 
[10]  Bodnar, L.M., M.E. Cogswell, and K.S. Scanlon, Low income postpartum women are at risk of iron deficiency. J Nutr, 2002. 132(8): p. 2298-302.
 
[11]  Aron-Wisnewsky, J., et al., Nutritional and Protein Deficiencies in the Short Term following Both Gastric Bypass and Gastric Banding. PLoS One, 2016. 11(2): p. e0149588.
 
[12]  Cogswell, M.E., et al., Iron supplementation during pregnancy, anemia, and birth weight: a randomized controlled trial. Am J Clin Nutr, 2003. 78(4): p. 773-81.
 
[13]  Hyder, S.M., et al., Do side-effects reduce compliance to iron supplementation? A study of daily- and weekly-dose regimens in pregnancy. J Health Popul Nutr, 2002. 20(2): p. 175-9.
 
[14]  Toblli, J.E., et al., Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound. Drug design, development and therapy, 2017. 11: p. 3401-3412.
 
[15]  Haas, J.D., et al., Iron-biofortified rice improves the iron stores of nonanemic Filipino women. J Nutr, 2005. 135(12): p. 2823-30.
 
[16]  Finkelstein, J.L., et al., A Randomized Trial of Iron-Biofortified Pearl Millet in School Children in India. J Nutr, 2015. 145(7): p. 1576-81.
 
[17]  Haas, J.D., et al., Consuming Iron Biofortified Beans Increases Iron Status in Rwandan Women after 128 Days in a Randomized Controlled Feeding Trial. The Journal of Nutrition, 2016. 146(8): p. 1586-1592.
 
[18]  Nestel, P., et al., The use of iron-fortified wheat flour to reduce anemia among the estate population in Sri Lanka. Int J Vitam Nutr Res, 2004. 74(1): p. 35-51.
 
[19]  Masuda, H., M.S. Aung, and N.K. Nishizawa, Iron biofortification of rice using different transgenic approaches. Rice (New York, N.Y.), 2013. 6(1): p. 40-40.
 
[20]  Qu le, Q., et al., Iron accumulation does not parallel the high expression level of ferritin in transgenic rice seeds. Planta, 2005. 222(2): p. 225-33.
 
[21]  Robuche et al., Microanalysis of non-heme iron in animal tissues J. Biochem. Biophys. Methods 58 (2004) 239-251).
 
[22]  Coe C.et al., Optimal iron fortification of maternal diet during pregnancy and nursing for investigating and preventing iron deficiency in young rhesus monkeys. Res in Veterinary Science 94 (2013). 549-554.
 
[23]  Lubach GR and Coe CL., Preconception Maternal Iron Status is a Risk Factor for Iron Deficiency in Infant Rhesus Monkeys. J Nutrition 136 (2006) 2345-2349.
 
[24]  Shawki, A., et al., Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese. Am J Physiol Gastrointest Liver Physiol, 2015. 309(8): p. G635-47.
 
[25]  Leong, W.I., et al., Iron supplementation during infancy--effects on expression of iron transporters, iron absorption, and iron utilization in rat pups. Am J Clin Nutr, 2003. 78(6): p. 1203-11.
 
[26]  Fleming, R.E., et al., Mechanism of increased iron absorption in murine model of hereditary hemochromatosis: increased duodenal expression of the iron transporter DMT1. Proc Natl Acad Sci U S A, 1999. 96(6): p. 3143-8.
 
[27]  Korolnek, T. and I. Hamza, Like iron in the blood of the people: the requirement for heme trafficking in iron metabolism. Frontiers in Pharmacology, 2014. 5(126).
 
[28]  Qiu, A., et al., Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell, 2006. 127(5): p. 917-28.
 
[29]  Suzuki, Y.A., V. Lopez, and B. Lönnerdal, Mammalian lactoferrin receptors: structure and function. Cell Mol Life Sci, 2005. 62(22): p. 2560-75.
 
[30]  Roiron-Lagroux, D. and C. Figarella, Evidence for a different mechanism of lactoferrin and transferrin translocation on HT 29-D4 cells. Biochemical and Biophysical Research Communications, 1990. 170(2): p. 837-842.
 
[31]  Mikogami, T., et al., Apical-to-basolateral transepithelial transport of human lactoferrin in the intestinal cell line HT-29cl.19A. Am J Physiol, 1994. 267(2 Pt 1): p. G308-15.
 
[32]  Federico, B., et al., Efficacy of lactoferricin B in controlling ready-to-eat vegetable spoilage caused by Pseudomonas spp. Int J Food Microbiol, 2015. 215: p. 179-86.
 
[33]  Actor, J.K., S.A. Hwang, and M.L. Kruzel, Lactoferrin as a natural immune modulator. Curr Pharm Des, 2009. 15(17): p. 1956-73.
 
[34]  Nuijens, J.H., P.H. van Berkel, and F.L. Schanbacher, Structure and biological actions of lactoferrin. J Mammary Gland Biol Neoplasia, 1996. 1(3): p. 285-95.
 
[35]  Theil, E.C. et al. Absorption of Iron from Ferritin is Independent of Heme Iron and Ferrous Salts in Women and Rat Intestinal Segments. J. Nutr. 142: 478-483, 2012
 
[36]  Lönnerdal, B., et al., Iron absorption from soybean ferritin in nonanemic women. Am J Clin Nutr, 2006. 83(1): p. 103-7.
 
[37]  Chiou, B. and J.R. Connor, Emerging and Dynamic Biomedical Uses of Ferritin. Pharmaceuticals (Basel), 2018. 11(4).
 
[38]  Todorich, B., X. Zhang, and J.R. Connor, H-ferritin is the major source of iron for oligodendrocytes. Glia, 2011. 59(6): p. 927-35.
 
[39]  Arosio, P., et al., Characteristics of ferritins in human milk secretions: similarities to serum and tissue isoferritins. Clin Chim Acta, 1986. 161(2): p. 201-8.
 
[40]  Chang, Y.J., et al., Recovery from iron deficiency in rats by the intake of recombinant yeast producing human H-ferritin. Nutrition, 2005. 21(4): p. 520-4.
 
[41]  Goto, F., et al., Iron fortification of rice seed by the soybean ferritin gene. Nat Biotechnol, 1999. 17(3): p. 282-6.
 
[42]  Sczekan SR and Joshi JG Isolation and characterization of ferritin from soybean. J Biol Chem (1987) 262:13780-13788.