Detail-Document #240811

This Detail-Document accompanies the related article published in

PHARMACISTS LETTER / PRESCRIBERS LETTER

August 2008 ~ Volume 24 ~ Number 240811

Comparison of Oral Iron Supplements

A new iron supplement product in the U.S. called Ferralet 90 is adding to the confusion surrounding
the numerous oral iron supplements on the market. Ferralet 90 is a combination product containing
carbonyl iron, B12, vitamin C, folic acid, and docusate and it is marketed as a prescription product. No
oral iron dietary supplements are approved by the FDA, but manufacturers can choose to market their
products as prescription only.8 There are two main iron salts forms (ferric and ferrous irons) and
numerous formulations (e.g., amino-acid chelates, carbonyl iron, polysaccharide-iron complex,
combination products, extended-release products, etc) available in the U.S. and Canada. All dietary iron
has to be reduced to the ferrous form to enter the mucosal cells; therefore ferrous iron is absorbed three
times more readily than the ferric form. Anecdotal claims that sustained-release iron preparations cause
fewer gastrointestinal side effects have not been well substantiated.1,2 There is some evidence that
controlled-release iron preparation causes less nausea and epigastric pain than conventional ferrous
sulfate, but the discontinuation rates are similar.3 Theoretically, once-daily dosing can improve
compliance. However, extended-release or enteric-coated formulations have been found to transport iron
past the duodenum and proximal jejunum, thereby reducing the absorption of iron.1,2 Vitamin C is added
to some products to enhance iron absorption. About 200 mg is needed to increase absorption of 30 mg of
elemental iron.1 However, doses of 500 mg to 1000 mg only increase iron absorption by about 10%.2
Most iron preparations containing vitamin C dont have a sufficient amount of vitamin C to substantially
affect iron absorption.1,2 In general, iron supplements should be taken on an empty stomach since food
can decrease absorption by 40% to 50%. GI side effects such as nausea and abdominal pain occur more
frequently as the quantity of soluble elemental iron in contact with the stomach and duodenum increases.
Higher iron doses also increase the occurrence of constipation.1,10 Therefore, there should be no
difference in GI tolerance when an equal quantity of elemental iron is administered regardless of the form
of iron salt.2 A chart summarizing the differences among the various iron formulations is included.

Comparison of Oral Iron Salts and Formulations

Formulation
Carbonyl iron
(U.S. Only)

Brand
Names
Feosol with
Carbonyl
Iron, Ferracap,
Ferralet 90
Icar, Iron
chews, etc.

% Elemental
Iron 1,2(w/w)
100

Dosage
Forms
Tablets,
chewable
tablets,
suspension

Comments

Consists of microparticles of
highly purified elemental iron;
not an iron salt.1
Provides the highest amount of
elemental iron.
Dissolves in gastric secretion
and is converted to
hydrochloride salt prior to
absorption in the stomach.1
Absorption rate is slow, which
permits continued release of
iron for 1 to 2 days.4
Less toxic than iron salts.4,5
Requires much higher dosage
to cause toxicity compared to
ferrous sulfate.4,5

More. . .
Copyright 2008 by Therapeutic Research Center
Pharmacists Letter / Prescribers Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249
www.pharmacistsletter.com ~ www.prescribersletter.com

(Detail-Document #240811: Page 2 of 4)

Formulation
Cont.
Ferric
ammonium
citrate4

Brand
Names

% Elemental
Iron 1,2(w/w)

Iron Citrate

18

Dosage
Forms
Capsules

(U.S. &
Canada)

Comments

Ferrous
bisglycinate4
(U.S. Only)

Bluebonnet
Chelated
Iron Albion,
Amino Acid
Chelate
Ferrochel,
etc.

20

Capsules,
tablets

Ferrous
fumarate

Ferrous
gluconate

FerroSequels
time-release
tablets,
Nephro-Fer,
Ferretts,
Repliva, etc.
Canada:
Palafer,
Neo Fer
Pediafer,
etc.
Fergon,
Floradix,
etc.
Canada:
ApoFerrous
Gluconate,
etc.

33
(Please note
Repliva contains
two types of iron)

12

Tablets,
chewable
tablets

Tablets

Most commonly used ferric

salt.4
Requires reduction to ferrous
form in the intestinal lumen.4
Less bioavailable than ferrous
salts.4
Less poisoning potential since
the GI tract has limited
capacity to reduce it to ferrous
form.

An iron-amino acid chelate.

Relatively high bioavailability.
Theoretically, the conjugation
of ferrous iron with amino acid
prevents the iron from forming
insoluble ferric hydroxide in
the small intestine.
May be less likely to cause GI
intolerance than ferrous
sulfate, ferrous gluconate, or
ferrous fumerate.5

Similar efficacy and

tolerability as ferrous sulfate.
Moderately soluble in water.
Almost tasteless.4
Repliva also contains Sumalate
(ferrous asparto glycinate)
a
which is a chelated iron.

Similar efficacy and

tolerability as ferrous sulfate.1,2

More. . .
Copyright 2008 by Therapeutic Research Center
Pharmacists Letter / Prescribers Letter ~ P.O. Box 8190, Stockton, CA 95208
Phone: 209-472-2240 ~ Fax: 209-472-2249
www.pharmacistsletter.com ~ www.prescribersletter.com

(Detail-Document #240811: Page 3 of 4)

Formulation
Cont.
Ferrous sulfate

Ferrous
sulfate, dried

Heme-iron
polypeptide

Brand
Names

% Elemental
Iron 1,2(w/w)

Dosage
Forms

Feosol with
Ferrous
Sulfate,
FeroSul,
Fer-In-Sol,
Fer-GenSol, etc.

20

Oral solution,
tablets,
enteric-coated
tablets, filmcoated tablets

Formulation of choice for

treatment of iron-deficiency
anemia given its general
tolerability, effectiveness, and
low cost.1,2

30

Capsules,
tablets,
extendedrelease tablets

Formulation of choice for

treatment of iron-deficiency
anemia given its general
tolerability, effectiveness, and
low cost.1,2

Capsules

Hemaglobin extracted from

porcine red blood cells.7
More bioavailable than iron
salts.7
Well-tolerated.
Heme iron is classified as a
medical food rather than a
supplement, because it is
derived from a food (animal)
source.

Canada:
Fero Grad,
Fer-In-Sol,
Ferodan,
etc.
Feratab,
Slow FE,
etc.
Canada:
Slow FE
Proferrin
ES,
Proferrin
Forte

1006

Canada:
Proferrin

Polysaccharide Niferex,
-iron complex Niferex-150,
Ferrex 150,
etc.
Canada:
Triferexx

Comments

1009

Capsules,
solution, filmcoated tablets

Ferric iron is complexed to

hydrolyzed starch, making it
tasteless and odorless.
Similar bioavailability as
ferrous sulfate.
Promoted to cause less GI
irritation, but the claim is
unproven.

a. Theoretically, chelated irons are better tolerated and absorbed compared to other forms of iron. Refer
to ferrous bisglycinate regarding details of chelated irons. Note that there are no clinical trials to prove
that ferrous asparto glycinate (Sumalate) is better tolerated or absorbed than other forms of iron.11
Users of this document are cautioned to use their own professional judgment and consult any other necessary or
appropriate sources prior to making clinical judgments based on the content of this document. Our editors have
researched the information with input from experts, government agencies, and national organizations. Information
and Internet links in this article were current as of the date of publication.

More. . .
Copyright 2008 by Therapeutic Research Center
Pharmacists Letter / Prescribers Letter ~ P.O. Box 8190, Stockton, CA 95208
Phone: 209-472-2240 ~ Fax: 209-472-2249
www.pharmacistsletter.com ~ www.prescribersletter.com

(Detail-Document #240811: Page 4 of 4)

Project Leader in preparation of this DetailDocument: Wan-Chih Tom, Pharm.D.

References
1.

2.

3.

4.
5.

McEvoy GK, ed. AHFS Drug Information. Iron

preparations, oral. AHFS 2007 Drug Information.
Bethesda, MD: American Society of HealthSystems Pharmacists, Inc; 2007, 1410-7.
Bolinger AM, Korman NR. Chapter 49. Anemias.
In: Koda-Kimball MA, Young LY, Eds. Applied
th
Therapeutics: The Clinical Use of Drugs. 4 ed.
Vancouver, WA: Applied Therapeutics , Inc. 1990:
1051-68.
McDiarmid T, Johnson ED. Clinical inquiries. Are
any oral iron formulations better tolerated than
ferrous sulfate? J Fam Pract 2002;51(6):576.
Nagpal J, Choudhury P. Iron formulations in
pediatric practice. Indian Pediatr 2004:41:807-15.
Anon.
Product Review:
iron supplements.
ConsumerLab.com. May 5, 2008.

6.

Personal communication.
Sonia. Medical
Information Dept. Colorado Biolabs, Inc. Cozad,
NE 69130. June 2008.
7. Seligman PA, Moore GM, Schleicher RB. Clinical
studies of HIP:
An oral heme-iron product.
Nutrition Research 2000;20:1279-86.
8. Personal communication. S. Cianci. Center for
Food Safety and Applied Nutrition. FDA. May 1,
2008.
9. Personal communication.
Michelle.
Medical
Information Dept. Ther-Rx Corp. Bridgeton, MO
63044. June 2008.
10. Jellin M, Gregory PJ, et al. Iron monograph.
Natural Medicines Comprehensive Database.
http://www.naturaldatabase.com. (Accessed July
18, 2008).
11. Personal communication.
Nathan.
Medical
Information Department. Ther-Rx Corp. Bridgeton,
MO 63044. (July 23, 2008).

Cite this Detail-Document as follows: Comparison of oral iron supplements. Pharmacists Letter/Prescribers
Letter 2008;24(8):240811.

Evidence and Advice You Can Trust

3120 West March Lane, P.O. Box 8190, Stockton, CA 95208 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249
Copyright 2008 by Therapeutic Research Center

Subscribers to Pharmacists Letter and Prescribers Letter can get Detail-Documents, like this one, on any
topic covered in any issue by going to www.pharmacistsletter.com or www.prescribersletter.com