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science and iron

Science and Safety of
Polysaccharide-Iron Complex (PIC)

Iron is one of the most common minerals on the planet, yet iron deficiency is paradoxically the most prevalent nutritional deficiency; some of this is due to the mechanism of iron absorption.

Dietary iron comes in two forms:

  • Heme form found in meat and fish is readily absorbed
  • Non-heme form found in cereals, beans and spinach is less readily absorbed

Only small quantities of iron are absorbed in the small intestine at a time, and non-heme iron needs to be transformed into its ferrous form and bound to a transporter to pass from the gut into the bloodstream. Once in the bloodstream, iron is used in the bone marrow to make hemoglobin and the excess iron is stored as ferritin primarily in the liver and some in the spleen.

Iron deficiency is widespread and severely compromises health, cognition, productivity, and longevity. The World Health Organization calculates that 30% of the world’s population suffers from anemia, many due to iron deficiency.

Those at greatest risk include:

  • Infants and children
  • Menstruating girls and women
  • Pregnant women
  • Premenopausal women
  • Vegetarians and vegans
  • Patients undergoing hemodialysis
  • Individuals who have had gastric bypass or bariatric surgery
  • Those with HIV/AIDS or malaria.

For these affected individuals, iron supplementation is necessary to restore health and function.

Supplemental iron can be provided in ferrous (Fe2+) or ferric (Fe3+) forms. The recommended daily allowance for healthy individuals, according to Health Canada, is 8-11 mg/day for men, 18 mg/day for women of childbearing age, 27 mg/day for pregnant women and 8 mg/day for other women. These doses can be increased for individuals with iron deficiency after consulting with a doctor. Iron supplements are generally manufactured as iron salts, such as ferrous fumarate, ferrous sulfate, and ferrous gluconate. A new iron formulation called Polysaccharide-Iron Complex (PIC), found in FeraMAX®, was introduced to the Canadian market. Of these, PIC delivers the highest dose of iron with 150 mg of elemental iron; ferrous fumarate delivers approximately 100 mg, with ferrous sulfate and ferrous gluconate delivering 65 and 35 mg respectively.

Many individuals suffer from the side effects of iron supplements, which include nausea, vomiting, epigastric pain, and constipation (Manoguerra et al., 2005). The rapid-release iron salts such as ferrous fumarate and ferrous sulfate have been associated with a higher incidence of unwanted side effects. Individuals experiencing these side effects are less likely to adhere to the recommended dosage and frequency prescribed by their physician (Melamed et al., 2007). This can lead to a serious deterioration of health, especially for pregnant women and infants.

The innovation of iron compounds that have greater bioavailability and fewer side effects led to the production of polysaccharide-iron complex (PIC) (Montgomery and Jhaveri, 1974) such as FeraMAX. In this process, PIC is synthesized by mixing ferric chloride and a saccharide with water, creating a product neutral and insoluble between pH 4.0–4.6, but positively charged and soluble at pH4.0 (Bereman and Berg, 1989). This makes it suitable to be digested in the human gastric system. X-ray powder diffraction analysis of the PIC revealed that it had the structure of a ferrihydrite (ᵝ-FeOOH) closely resembling the body’s natural iron binding protein, ferritin (Bereman and Berg, 1989) (Coe et al., 1995a, 1995b). The fact that the PIC closely resembles endogenous carriers of iron could account for its high bioavailability and reduced side effects as it is already in a readily absorbed formulation. PIC delivers the highest concentration of bioavailable iron,150 mg, with the lowest reported incidence of unwanted side effects.

Iron supplementation can benefit health, but it can also cause iron toxicity and side effects. Humans control iron levels by increasing or decreasing iron absorption in the intestines according to the body’s needs. Iron is excreted at a steady rate and there is no mechanism to increase iron elimination in case of overload. High iron levels can cause tissue damage because iron promotes the formation of free radicals. Toxicity is also a potential problem for infants and children given iron supplements; therefore they generally receive liquid iron supplements.

High doses of iron can be toxic, especially for children. PIC has a low toxicity compared with iron-salt compounds (Klein-Schwartz, 2000). This is calculated as an LD50.

The LD50 of PIC in rats was not established because no deaths occurred during a toxicology study. In children, accidental overdose of iron caused more than 30% of all deaths due to accidental ingestion of drugs between 1983 and 1991 (Manoguerra et al., 2005). In a study of 810 cases of potentially toxic ingestion of PIC that were reported to the American Association of Poison Control Centers, no serious adverse effects were reported for any of these cases (Klein-Schwartz, 2000). This analysis indicates a very low toxicity of PIC compared with iron-salt supplements.

In summary, iron is a crucial nutrient in the maintenance of good health, and some individuals require iron supplementation. Supplemental iron in the form of iron-salts (ferrous fumarate and ferrous sulfate) has unwanted side effects such as epigastric pain, nausea, vomiting, and constipation. Some individuals stop taking their physician-prescribed supplement because of these side effects, which negatively impacts health. A more tolerable iron supplement has been developed that delivers a high concentration of bioavailable iron with reduced or absent side effects; this product is a Polysaccharide-Iron Complex (PIC) that resembles ferrihydrite or the intracellular protein ferritin. FeraMAX® 150 and FeraMAX® Powder (pleasant tasting powder) are a PIC that delivers with virtually no unwanted side effects. Polysaccharide-iron supplements are widely prescribed by physicians to treat anemia, pregnancy-related iron deficiency and pre-term infant anemia, as well as iron supplementation for individuals with gastric bypass or bariatric surgeries, and those receiving dialysis (Johnson et al., 1992; Glassman, 1992; Markowitz et al., 1997; Naude et al., 2000; Zhang et al., 2012). Anecdotal evidence from some of these individuals on health message boards reveals the strong endorsement of PICs such as FeraMAX® by users because of their efficacy, and the absence of unwanted side effects.

References

  • Health Canada website: http://www.hc-sc.gc.ca/fn-an/alt_formats/hpfb-dgpsa/pdf/nutrition/dri_tables-eng.pdf
  • Bereman, R.D., Berg, K.A. (1989) The structure, size and solution chemistry of a polysaccharide iron complex (niferex). InorganicaChimicaActa, 155, pp. 183-189.
  • Beshara, S., Sorensen, J., Lubberink, M., Tolmachev, V., Langstrom, B., Antoni, G., Danielson, B.G., Lundqvist, H. (2003) Pharmacokinetics and red cell utilization of 52Fe/59Fe-labelled iron polymaltose in anaemic patients using positron emission tomography. British Journal of Haematology, 120(5), pp. 853-859.
  • Coe, E.M., Bowen, L.H., Speer, J.A., Wang, Z., Sayers, D.E., Bereman, R.D. (1995a) Therecharacterization of a polysaccharide iron complex (niferex). Journal of Inorganic Biochemistry, 58(4), 269-278.
  • Coe, E.M., Bowen, L.H., Speer, J.A., Bereman, R.D. (1995b) Comparison of polysaccharide iron complexes used as iron supplements. Journal of Inorganic Biochemistry, 57(4), pp. 287-292.
  • Glassman, E. (1992) Oral iron therapy with ferrous fumarate and polysaccharide iron complex. ANNA Journal, 19(3), pp. 277-278.
  • Johnson, C.A., Rosowski, E., Zimmerman, S.W. (1992) A prospective open-label study evaluating the efficacy and adverse reactions of the use of Niferex-150 in ESRD patients receiving EPOGEN. Adavnaces in Peritoneal Dialysis, 8, pp. 444-447.
  • Klein-Schwartz, W. (2000) Toxicity of polysaccharide-iron complex exposures reported to poison control centers. The Annals of Pharmacotherapy, 34, pp. 165-169.
  • Manoguerra, A.S., et al. (2005) Iron ingestion: An evidence-based consensus guideline for out-of-hospital management. Clinical Toxicology, 43, 553-570.
  • Markowitz, G.S., Kahn, G.A., Feingold, R.E., Coco, M., Lynn, R.I.An evaluation of the effectiveness of oral iron therapy in hemodialysis patients receiving recombinant human erythropoietin.Clinal Nephrology, 48(1), pp. 34-40.
  • Melamed, N., Ben-Haroush, A., Kaplan, B., Yogev, Y. (2007) Iron supplementation in pregnancy – Does the preparation matter? Archives Gynecological Obstetrics, 276(6), pp. 601-604.
  • Merriman, T.N. (1994) An acute oral toxicity study in rats with polysaccharide iron complex. Springborn Laboratories Life Science Division Study No. 3340.1, pp. 1-40.
  • Montgomery K.O., Jhaveri, C.R. (1974) Process for preparing an iron-saccharide complex.United States Patent 260/209R, 260/209D, 424/361.
  • Naude, S., Clijsen, S., Naulaers, G., Daniels, H., Vanhole, C., Devlieger, H. (2000) Iron supplementation in preterm infants: A study comparing the effect and tolerance of a Fe2+ and a nonionic FeIII compound. Journal of Clinical Pharmacology, 40, pp. 1447-1451.
  • Pfizer. (2007) Material safety data sheet: Ferrous fumarate.
  • http://www.pfizer.com/files/products/material_safety_data/609.pdf [Accessed 11 December 2012].Teckcominco. (2003) Material safety data sheet: Ferrous sulphate.
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  • Zhang, Z.S., Wang, X.M., Han, Z.P., Yin, L., Zhao, M.X., Yu, S.C. (2012) Physicochemical properties and inhibition effect on iron deficiency anemia of a novel polysaccharide-iron complex (LPPC). Bioinorganic Medical Chemistry Letters, 22(1), pp. 489-492.