What is Sanferol?

Sanferol® (Sodium Ferrous Citrate, hereinafter referred to as SFC), an iron fortifier, is odorless and greenish white powder, and soluble chelated iron (non-ionic iron). It contains 10.0 to 11.0% iron.1) It is synthesized from ferrous sulfate and sodium citrate. Because it is free from allergens, genetically modified organisms (GMO), and products of biological origin, Sanferol® is a very safe substance. It can be widely used as a food additive and supplement ingredient.

In Japan, Sanferol® has been used in various foods such as baby milk powder, school and hospital food, beverages, cereals and supplements. On May 10, 2013, the US FDA recognized SFC as a Substance Generally Recognized as Safe (GRAS).

Intended uses of Sanferol®

Sodium Ferrous Citrate (SFC), the ingredient of Sanferol®, is stable to heating to about 270°C (518°F) and slightly hygroscopic. Due to its high solubility at acidic to basic pH values (between 1 and 8)1) and stability in solutions,2)3) it can be used in beverages such as sport and energy drinks. In addition to its heat stability, it reacts less with other food ingredients, for example, tannic acid4) and phytic acid,5) than with other iron materials, leading to good processability. Accordingly, Sanferol® can be used in processed foods such as retort foods, cereals, and baked cakes.

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No inhibition of SFC absorption in the presence of calcium

It is known that the absorption of iron in general is inhibited in the presence of calcium. The absorption of SFC, the ingredient of Sanferoi®, is not affected in the presence of calcium levels present in food.7) Sanferol® can be prescribed as supplemental tablets along with calcium.

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High absorption (Specific mechanism of SFC absorption)

Sanferol® exhibits high absorption. SFC, the ingredient of Sanferol®, is soluble at a broad range of acidic to basic pH values because it seems to be present in the form of a low-molecular weight complex of iron chelated with citric acids. This chelate can be absorbed from the gastrointestinal tract, unlike high-molecular weight polymers resistant to absorption from the gastrointestinal tract. These insoluble polymers are formed after oxidation in a basic solution.8)9) Iron is mainly absorbed from the small intestine, especially from the duodenum and the superior portion of the jejunum. In the small intestine, SFC is considered to be mostly present in the form of chelated iron (non-ionic iron), which can be absorbed into intestinal cells as chelated iron. Because of its characteristic mechanism of absorption, SFC exhibits higher absorption than other iron materials such as ferrous sulfate and ferrous fumarate.

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Selective absorption (Inhibition of absorption of excessive iron in healthy people)

SFC, the ingredient of Sanferol®, is absorbed well in persons with iron deficiency but is absorbed little in persons whose blood iron parameters such as serum iron and ferritin are high-normal.10)11) These features prevent healthy normal persons from absorbing an excessive amount of iron from supplements containing iron. Thus, Sanferol® can be safely ingested by anybody who takes iron supplements.

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Effective in women with anemia as iron supplements

SFC, the ingredient of Sanferol®, is absorbed well by women with iron deficiency or anemia. Many reports show that SFC is effective for the treatment of anemia not only in non-pregnant women with anemia but also in pregnant and puerperal women with anemia.12)-15) It has also been reported that SFC preparation improved iron deficiency in a pregnant woman with iron deficiency anemia whose hemoglobin level had not increased after administration of other iron preparations such as ferrous fumarate.12) A dairy supplemental dose of SFC improved iron deficiency in young women with iron deficiency.16) In addition, it has been reported that SFC is transferred readily to the fetus through the placenta.15) Thus, Sanferol® is expected to be effective as an iron ingredient in supplements for women with iron deficiency.

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Advantages of chelated iron (non-ionic iron)

Since it can be soluble in the form of chelated iron (non-ionic iron) even in weak basic pH conditions, SFC, the ingredient of Sanferol®, releases fewer iron ions than other iron materials such as ferrous sulfate and ferrous fumarate. Thus, it irritates the gastric mucosa less than other iron materials.12) It reacts little with other ingredients contained in food and tea, and accordingly its absorption is hardly affected by foods and drinks. SFC can be absorbed well even after meals10) and in persons with hypoacidity such as the elderly with decreased secretion of gastric acids, patients undergoing therapy with antacids, and patients with gastrectomy.17)-19)

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Abundant clinical data

SFC, the ingredient in Sanferol®, has been used as the drug substance in Ferromia®, a prescription drug, in Japan since 1986. There are abundant clinical efficacy and safety data on SFC.12)-22)

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Absorption, distribution and excretion data

Absorption, distribution and excretion data demonstrate the high absorption of SFC.23)

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References:

1)
Ishino Y, Takashima M, Terashima C, Orimo Y (1988). Physicochemical properties and stability of tetrasodium biscitrato iron (II). Pharmaceutical Regulatory Science 19(1):44-52 [English Translation].
2)
In-house data (2005): “Stability of SFC and a fine iron powder preparation in solutions at various pH values” by Omura K, Honjo Laboratory Unit, Eisai Food & Chemical Co., Ltd. [English summary].
3)
In-house data (2004): “Sensory evaluation for SFC-added beverages” Omura K, Honjo Laboratory Unit, Eisai Food & Chemical Co., Ltd. [English summary].
4)
Shimozono T et al. (1988). Evaluation of factors which affect the reactivity of iron with tannic acids. J of New Remedies & Clinics 37(6): 1030-1034 [English summary].
5)
Terashima C et al. (1992). II. Sodium Ferrous Citrate: Iron Fortifier Materials: Tokyo, Japan: Japan Confectionery and Innovative Food Ingredients Research Center, pp.1-10 [English summary].
6)
In-house data (2002): Study report 20020261: Comparison of physico-chemical features of SFC to other iron materials (Marketing promotion data for SFC (Sanferol®). Iwata T, Eisai Co., Ltd.[English summary].
7)
In-house data (2004): Take K and Yoshimura H, Eisai Co., Ltd. [English summary].
8)
Fujita T, Terato K (1973). Approach to mechanism of intestinal iron absorption in terms of physicochemical properties of iron compounds. J of Clinical and Experimental Medicine 87(13):711-716 [English translation].
9)
Terato K, Fujita T, Yoshino Y (1973). Studies on iron absorption. I. The role of low molecular polymer in iron absorption. Am J Dig Dis 18(2):121-128 [English translation].
10)
Miyao S, Iwata N, Maekawa T (1984). Results of a phase I clinical study of E-0708. Jpn J Clin Exp Med 61(6):315-330 [English translation].
11)
Motoya T et al. (1989). The effect of green tea drinking on absorption of sodium ferrous citrate. Prog. Med. 9(3): 1293-1296. [English translation].
12)
Shoda S, Kozu H (1989). Treatment with Ferromia® for iron deficiency anemia. Parturient Blood 13(1): 77-82 [English summary].
13)
Terao T, Maki M, Suzuki M (1989). Multicenter clinical study on sodium ferrous citrate preparations as a treatment for anemia in pregnant women - Comparison with ferrous sulfate. Obstetrical and Gynecological Practice 38(2): 191-206 [English summary].
14)
Noda Y et al. (1994). The therapeutic effect of SFC on postpartum iron deficiency anemia. Perinatal Medicine 24(7):1001-1004 [English summary].
15)
Hayashi Y et al. (1989). Iron metabolism in pregnant women and cord blood findings. Obstetrical and Gynecological Practice 38(9):1319-1323 [English summary].
16)
Shirakura T, Kubota K, Tamura J, Kurabayashi H, Yanagisawa T, Sakurai T et al. (1988). Clinical research: Effects of iron-fortified jelly on iron deficiency. Clin Nutr 72(1):65-68 [English translation].
17)
Kariyazono H et al. (1993). Clinical research on iron absorption in patients who had gastrectomy. Surgical Metabolism and Nutrition 27(2): 107-112 [English summary].
18)
Johno I et al. (1992). Clinical research on iron absorption in patients who had a total gastrectomy. Medical Consultation and New Remedies 29(5): 1235-1240 [English summary].
19)
Hori M and Nishi M (1988). Therapeutic effects of oral administration of Ferromia® tablets in anemic patients after subtotal or total gastrectomy. Japanese J of Clinical and Experimental Medicine 65(9): 3033-3035 [English summary].
20)
Maekawa T et al. (1985). Clinical study of E-0708 on iron deficiency anemia - a multicenter double-blind comparative study with sustained-release ferrous sulfate iron preparations. The Japanese Journal of Clinical and Experimental Medicine 62 (8): 2615-2636 [English summary].
21)
Saeki T et al. (1992). Post marketing surveillance of sodium ferrous citrate (Ferromia®) - Detailed drug use surveillance on age and pregnancy factors. Pharmaceutical Regulatory Science (Special Number): 137-150 [English summary].
22)
Mitamura T, Kitazono M, Yoshimura O (1989). Influence of green tea on improvement of iron deficiency anemia associated with pregnancy: Treatment with sodium ferrous citrate. Acta Obst Gynace Jpn 41 (6): 688-694 [English summary].
23)
Ariyoshi T, Arizono K, Irishio K, Okanari E (1987). Drug Metab Pharmacokinet 2(1):3-10 [English translation].
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Sanferol is registered trademarks of Mitsubishi Chemical Co., Ltd.
Ferromia is registered trademarks of Eisai Co., Ltd. in Japan.