This white paper will discuss iron therapy in general, why it is sometimes problematic,mainly due to tolerance and practical issues for those suffering from iron deficiency. Important groups that are discussed in this aspect are children, young girls, fertile females, seniors and people with chronic diseases such as IBD, CHF, CKD that affect the iron metabolism and how Heme‐Iron supplementation change this situation. The target is to inform the medicinal and pharmaceutical communities of this relatively new form of therapy and why it has great benefits compared to the traditional methods.

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White paper
IRON THERAPY ­ WITHOUT PROBLEMS
MediTec FerroCare Division |
FerroCare@MediTec.SE
1.3 2016
ABSTRACT
Low iron counts is according to WHO one of the most common and life threatening
conditions worldwide. Iron cannot be substituted by any other nutrients in your food.
Suffering from low iron, no amount of vitamins or any other supplement is going to
assist to improve the lack of iron.
The symptoms of iron deficiency are so common that they are not always fully
recognized and may hence lead to further cause of health issues.
This white paper will discuss iron therapy in general, why it is sometimes
problematic,mainly due to tolerance and practical issues for those suffering from iron
deficiency.
Important groups that are discussed in this aspect are children, young girls, fertile
females, seniors and people with chronic diseases such as IBD, CHF, CKD that affect the
iron metabolism and how Heme‐Iron supplementation change this situation.
The target is to inform the medicinal and pharmaceutical communities of this relatively
new form of therapy and why it has great benefits compared to the traditional methods.

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PART 1. THE PRESENT SITUATION
­ Low iron counts are one of the most common conditions worldwide
­ Iron cannot be substituted by anything else
­ Common symptoms
­ The general iron uptake and causes of iron need
­ The importance of supplementation avoiding side­effects
­ All iron comes from the diet
Low iron counts are one of the most common conditions worldwide
More than one‐quarter of the world's population is anemic. Approximately one‐half of
this burden is a result of iron deficiency anemia, being most prevalent among preschool
children and women.
Globally, anemia affects 1.62 billion people (95% CI: 1.50–1.74 billion),which
corresponds to 24.8% of the population (95% CI: 22.9–26.7%).
The highest prevalence is in preschool‐age children (47.4%, 95% CI: 45.7–49.1), and the
lowest prevalence is in men (12.7%, 95% CI: 8.6–16.9%). However, the population
group with the greatest number of individuals affected is non‐pregnant women (468.4
million, 95% CI: 446.2–490.6). (WHO).
The diagnosis, prevention, and treatment of iron deficiency is obviously a major public
health goal, especially in low‐ and middle‐income countries.
Iron cannot be substituted by anything else
Iron is the most important part of the hemoglobin in the red blood cells that carry
oxygen to all the cells of the body. In case of shortage of iron in the body we easily run
short of breath, get tired and have problems concentrating even at low deficiency.
Our bodies contain 4‐5 grams of iron. It may be difficult to get enough of this important
nutrient unless meat courses are part of the continuous diet. Fruit, cereals and
vegetables contain very little of useful iron and so if you are suffering from low iron, no
amount of vitamins or any other supplement will assist the situation.
Common symptoms
Almost every third woman has low iron values. The risk is especially high if
menstruation lasts longer than three days, during pregnancy and lactation. During
menstruation the woman loses an average of 35‐40 mg of iron, or around 10 mg per day.

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This is why women need more iron intake on a regular bases than men.
The symptoms of iron depletion are so common that they are often not recognized.
Except for weakness and shortage of breath it will also affect appearance. The skin
grows pale and hair and nail lose strength and luster.
Iron deficiency can give the following symptoms:
‐ Tiredness, fatigue, passivity and drowsiness
‐ Concentration difficulties and increased need for sleep
‐ Impaired physical performance
‐ Lessened learning ability and decreased cognitive performance
The general iron uptake and causes for iron need
In healthy individuals the average iron absorbed is 1 mg daily for men, 1.5 ‐ 2.5 mg daily
for women and during pregnancy 2‐3 mg daily corresponding to a total of 500 ‐ 1 000
mg per month. Iron requirements should compensate for demand during growth,
pregnancy and physiological and pathological losses.
The importance of iron supplementation avoiding side­effects
Many iron supplementation treatments fail because synthetic iron produces painful,
uncomfortable and even dangerous due to gastro‐intestinal side‐effects. Iron is however
absolutely vital to life and bodily functions and hence the therapy must continue.
Heme‐Iron preparations avoid these harmful side‐effects as they have a virtually perfect
tolerance and as this will not change even in longer therapy use when necessary.
All iron comes from the diet
There are only two kinds of iron that we can use; Heme iron from meat, poultry, fish
and non‐heme iron from vegetables, dairy products and chemically bonded synthetic
iron in regular supplements.
Heme iron is taken up along the whole gastro‐intestinal tract (not only the first part)
and, unlike non‐heme iron, absorption is not affected by other chelating components of
the diet such as phytates, tannates and phosphate.

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PART 2. PATIENT GROUPS
­ Chronic diseases that affect iron metabolism
­ Importance of iron during pregnancy
­ Non­heme/synthetic iron is not absorbed when using Omeprazole
­ Anemia and Diabetes
­ Anemia and Heart Disease
­ Anemia and Chronic Kidney Disease
­ Anemia and Inflammatory bowel disease and iron depletion
­ Anemia and Inflammatory Diseases
­ Iron deficiency in young girls
­ Nutritional status and birth weight
­ It takes time to correct the situation of iron deficiency
­ Effect of supplementation on blood donors.
Chronic diseases that affect the iron metabolism
There is a large number of chronics in various diseases with anemia for instance Chronic
kidney disease, Inflammatory bowel disease and Coronary heart disease.
Chronics usually receive synthetic oral iron tablets in high doses until treatment fails
due to side‐effects. The remaining alternative is very expensive and inconvenient
intravenous iron. There are potential risks with repeated iron injections over a longer
period of time: overdosing and increased oxidative stress.
Importance of iron during pregnancy
Iron status of pregnant women and women who plan pregnancy determines the weight
of the fetus to such a degree that it affects the health status during the whole lifetime.
A negative iron balance causes not only physical and mental fatigue, but may also lead to
anemia. Iron deficiency in children may disturb the learning ability, which cannot be
substituted along the way. This concerns mainly psycho‐motor and cognitive
development plus further cognitive performance in life.
Non­heme/synthetic iron not absorbed when using Omeprazole
Achlorhydria refers to states where the production of gastric acid in the stomach is
absent or low and impairs protein digestion by inhibiting the activation of the
enzyme pepsin, whose activation is dependent upon a low gastric pH.
As acid facilitates non‐heme iron absorption, about 25% of achlorhydric patients

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develop iron‐deficiency anaemia. Because gastric acid releases Fe3+ from food and
reduces it to ferrous iron (Fe2+), achlorhydria reduces iron absorption.
Omeprazole is an acid‐reducer that is used to treat acid reflux and stomach ulcers and is
taken by iron‐deficient individuals as part of the treatment for upper GI tract disorders
that may or may not have been the primary cause of their anemia.
Lack of stomach acid caused by chronic use of Omeprazole can affect the absorption of
nutrients such as iron from foods. Patients taking Omeprazole for chronic stomach
disorders may require iron injections to prevent iron deficiency anemia which can be
substituted with Heme‐Iron therapy with no side‐effects and excellent efficiency.
Anemia and Heart Disease
Anemia, or a low hemoglobin level in the blood, is often linked to heart disease because
the heart has to work harder to pump more blood and oxygen through the body.
Heart failure is a very common disease, with severe morbidity and mortality, and a
frequent reason of hospitalization. Anemia and a concurrent renal impairment are two
major risk factors contributing to the severity of the outcome and consist of the
cardio‐renal anemia syndrome.
Anemia in heart failure is complex and multi‐factorial. Hemodilution, absolute or
functional iron deficiency, activation of the inflammatory cascade, and impaired
erythropoietin production and activity are some patho‐physiological mechanisms
involved in anemia of the heart failure.
Cardiovascular diseases are among the most frequent causes of death worldwide. Heart
failure is an enormous medical and societal burden and a leading cause of
hospitalization. It is estimated that 2.6 millions hospitalizations annually in the USA are
due to heart failure as a primary or secondary diagnosis.
Anemia of chronic inflammation is the most common cause of anemia and occurs in 58%
of heart failure patients with anemia. Anemia of inflammation and chronic disease is a
type of anemia that commonly occurs with chronic, or long term, illnesses or infections.
Anemia is common in patients with heart disease. It is present in approximately one
third of patients with congestive heart failure (CHF) and 10% to 20% of patients with
coronary heart disease (CHD).
Anemia and Chronic Kidney Disease
Chronic Kidney Disease (CKD) is a gradual and usually permanent loss of kidney
function over time. This happens over time, usually months to years.

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CKD is divided into 5 stages of increasing severity. Stage 5 chronic kidney failure is also
referred to as end‐stage renal disease. In Stage 5 there is total or near‐total loss of
kidney function and patients need dialysis or transplantation to stay alive.
(http://www.aakp.org)
CKD may be the result of physical injury or a disease that damages the kidneys, such as
diabetes or high blood pressure. When the kidneys are damaged, they do not remove
wastes and extra water from the blood as well as they should.
Anemia develops when the kidneys fail to produce enough erythropoietin, EPO, the
hormone that directs the bones to make red blood cells.
Anemia tends to worsen as CKD progresses and can itself cause heart problems.
CKD patients become anaemic primarily due to impaired absorption of iron, blood loss
into the gastro‐intestinal tract, and inadequate production of erythropoietin from the
kidneys. The management of patients not undergoing dialysis involves stepwise
treatment with oral iron, intravenous iron, and erythropoietin stimulating agents
(ESA’s).
Anemia and Inflammatory bowel disease and iron depletion
Inflammatory Bowel Disease, (IBD), is a condition that causes irritation and ulcers in
the gastrointestinal tract. It is a group of inflammatory conditions of the large intestine
and, in some cases, the small intestine.
The most common for IBD are ulcerative colitis and Crohn's disease. Anemia caused by
iron deficiency due to gastrointestinal blood loss and reduced iron absorption due to
inflammation is often present.
Inflammatory Bowel Disease (IBD), diseases that cause inflammation and irritation in
the intestines is often associated with iron deficiency and anemia.
It may also be exacerbated by a restrictive diet. In the US it is estimated that currently 1
– 1,3 million people are suffering from IBD. Crohn's disease and Ulcerative Colitis have
together and incidence of 339 per 100 000 adults (cdc.gov) and the number is higher in
Europe and increasing everywhere in the world.
Treatment today consists mainly of oral synthetic iron prior to intravenous iron and
erythropoietin treatment. The prevalence of intolerance towards oral synthetic iron is
however high, around 25‐30 %.
The absorption of Heme‐Iron is several times higher and the side‐effects rate
significantly lower than for non‐heme synthetic oral iron as heme iron is absorbed
through a separate pathway and does not have to be discontinued when intravenous
treatment is started. This can allow for longer intervals between resource‐heavy,
inconvenient and painful injections. Intravenous treatment is usually started only when
oral non‐heme treatment fails due to side‐effects.

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Anemia and Inflammatory Diseases
Inflammatory diseases that can lead to AI/ACD (Anemia of Inflammation and Anemia
Chronic Disease) including rheumatoid arthritis, which causes pain, swelling, stiffness,
and loss of function in the joints, lupus, which causes damage to various body tissues,
such as the joints, skin, kidneys, heart, lungs, blood vessels, and brain.
Iron deficiency in young girls
Low iron counts and even anaemia due to iron deficiency is a widespread problem.
Among adolescent girls, it will bring negative consequences on growth, school
performance, morbidity and reproductive performance. It also has several negative
physical symptoms such as tiredness, headaches and difficulty to concentrate.
Adolescents, especially girls, are particularly vulnerable to iron deficiency. ​The highest
prevalence is between the ages of 12‐15 years when requirements are at a peak. In all
Member States of the South‐East Asia Region, except Thailand, more than 25% of
adolescent girls are reported to be anaemic; in some countries as high as 50%.
(WHO,http://www.searo.who.int/entity/child_adolescent/documents/sea_cah_2/en/)
While approximately 8% of women are estimated to be iron deficient in the west, Dr
Mike Nelson, a nutritionist at King's College, London University, believes that between
10 ‐ 20 % of younger girls are affected. Although these girls often appear to be in good
health, low iron levels profoundly affect many aspects of their day to day lives, including
an ability to concentrate, and thus learn, in school. Nelson tells us, "In tests we have
carried out we think that the IQ in British girls who get enough iron in their diets and
those who are anaemic can mean the difference of a whole grade in school exams".
"Girls who are dieting and those switching to a vegetarian diet are particularly at risk",
explains Nelson: "New vegetarians need to be very careful in the first year of conversion
because they often cut out meat and don't know how to replace the iron with other
foods. Women and girls who diet and go vegetarian at the same time should think about
eating iron fortified foods or even taking a modest supplement". (European Food
Information Council, http://www.eufic.org/article/en/artid/iron‐common‐deficiency/)
Foods containing heme iron (meat, poultry, and fish) enhance iron absorption from
foods that contain non‐heme iron. ​Adolescent girls and fertile females in general are at
risk for iron deficiency mainly due to a small constant loss of blood through
menstruation. Another factor today is a diet with little or no meat​, poultry, and fish since
heme iron from meat products is central for a normal iron balance.
The problem is compounded when an adolescent girl gets a recommendation for
supplement iron and the product brings side‐effects, like the regular synthetic
supplements regularly do. The effect is a termination of the therapy and the situation for
the young female remains the same.

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Nutritional status and birth weight
English Professor David Barkers epidemological research studies show that the
nutritional status of the mother, mainly as hemoglobin count has an effect on fetal
development. This has also been tied to the health of the infant throughout life.
From the beginning of the century new‐born babies weight as well as the placenta has
been recorded.
We know today that a low nutritional status, above all low hemoglobin values in the
mother, is reflected in placental weight versus baby weight. By combining these data for
more than 5 000 persons and comparing them with health development throughout life
certain conclusions could be drawn.
It turns out that those born by mothers with low nutritional status suffered from various
internal diseases such as low blood pressure and diabetes to a higher degree, an
increased risk of coronary heart disease and the disorders related to it: stroke,
non‐insulin dependent diabetes, raised blood pressure, and the metabolic syndrome
A substantial number of studies show that mineral and vitamin supplements especially
during the vital first trimester has a decisive influence on maternal nutritional status
and birth weight of the baby.
The "fetal origins hypothesis", states that cardiovascular disease and non‐insulin
dependent diabetes originate through adaptations that the fetus makes when it is
undernourished. These adaptations may be cardiovascular, metabolic or endocrine and
include slowing of growth, they permanently change the structure and function of the
body.
It takes time to correct the situation of iron deficiency
The process of building up adequate iron stores takes months, much in the same way
that depletion does not happen overnight.
This is why supplementary dosage usually is enough. If the dosage is higher than 50 mgs
per day zinc absorption will be blocked.
The success of any iron therapy is closely related to user friendliness. This means that
tolerance and dosage‐related compliance is of central importance.
Effect of supplementation on blood donors.
Since blood donation is voluntary and this is a free service for the fellow man it is
natural to ”guard the sources”. This means that blood donors should receive iron
supplementation to compensate for iron loss from the blood donated, especially if​ ​low

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values are detected. This is not always the case because of low efficacy and frequent
side‐effects from the synthetic iron given.
Side effects often lead to the donors stopping taking the supplements, which in turn
means that they can only donate blood perhaps once or twice a year instead of normally
three times.
There are factors influencing synthetic iron absorption itself. Among these are tannins
in tea and coffee. Phytates in whole grain bread, milk proteins, albumin and soy proteins
may also reduce absorption.
This means that a regular diet and synthetic supplements may not be enough to
compensate for iron loss.
Heme‐Iron absorption is not affected by any of these factors.
Synthetic supplements at 100 mg Fe++ per dose regularly have an incidence of
side‐effects leading to termination of the therapy of around 30 %. Donors that have
previous negative experiences will usually not take the supplements at all.
It has been observed that after a blood donation absorption of non‐heme iron practically
ceases for around four days. Heme‐Iron, however is absorbed normally.
PART 3. HEME IRON
Heme iron in meat courses is the most important source of iron
Heme iron uptake is five times more efficient than non­heme iron
You can avoid side­effects with heme iron
Heme iron is 100 % natural, not synthetic.
Heme iron is economical because..
Hemoglobin iron in therapy. What do we know? Clinical studies.
Heme iron in meat courses is the most important source of iron
There are two pathways for dietary iron. Heme iron, which is found in all meat products,
is absorbed efficiently and neatly as a whole unit.
The other kind is simply non‐heme iron and has to be broken down in the gut before the
iron can be absorbed. Most of the highly reactive free iron ions remains in the gut and
cause side‐effects such as constipation, diarrhea and stomach cramps. The uptake of
non‐heme iron is also affected by other foods consumed.

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All regular supplements are synthetic. They feature chemically bonded iron.
Heme‐Iron supplements are made with natural bovine hemoglobin.
Heme iron uptake is five times more efficient than non­heme iron
Heme iron is natural for man and still is the best and most efficient way of absorbing the
iron we all need to live and for our bodies to function properly.
In a normal diet heme iron from meat products play a large role. The synthetic iron
supplements today are often produce gastro‐intestinal side‐effects which in many cases
terminate the important therapy
Heme‐Iron therapy is reasonably priced and much lower than for instance intravenous
therapy in chronic cases. As Heme‐Iron has virtually no Side‐effects this will not ruin the
therapy and therefore Heme‐Iron therapy has a much higher success rate due to better
tolerance than non‐heme iron therapy.
Heme‐Iron is natural for man and still is the best and most efficient way of absorbing
the iron we all need to live and for our bodies to function properly. In a normal diet
heme iron from meat products plays a large role.
Unlike non‐heme iron, absorption is not affected by other chelating components of the
diet such as phytates, tannates and phosphate as Heme‐Iron will always be absorbed ‐
in all clinical situations. Heme‐Iron is absorbed from the beginning of the intestine,
which means it will work also for example with patients, who have had gut surgery.
The uptake and tolerance of Heme‐Iron will not change even over a longer time period.
This is good news for chronics, since synthetic iron will usually give problems with
uptake sooner or later. This means another form of therapy must be considered.
The absorption of Heme‐Iron is several times higher and the side‐effects rate
significantly lower than for non‐heme oral iron. Heme‐Iron is absorbed through a
separate pathway and does not have to be discontinued when intravenous treatment is
started. This can allow for longer intervals between resource‐heavy, inconvenient and
painful injections. Oxidative stress is also avoided. Heme‐Iron does not need to be
discontinued during injection or EPO therapy like non‐heme oral iron.
Heme‐Iron therapy has the simplest possible dosage: One or more tablets once per day,
at anytime and there is no need to consider other simultaneously ingested foodstuff or
drink.
Uptake for Heme‐Iron is 20 ‐ 40 %.
Heme‐Iron is very well tolerated. There are no known unpleasant side‐effects. Uptake or
tolerance will not change over time.

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Heme‐Iron has been used in large scale as an iron supplement in Scandinavia for over 30
years with no reported serious side‐effects or poisonings.
You can avoid side­effects with ​Heme­Iron
In studies the incidence of side‐effects with heme iron products is at placebo level.
The mechanism of uptake for heme iron does not leave free iron ions in the gut that may
cause disturbances and are potentially carcinogenic.
Heme iron is natural
All regular supplements are synthetic. They feature chemically bonded iron.
Heme iron supplements are made with natural bovine hemoglobin.
Heme iron is economical because.
With a dosage of one or two tablets once per day Heme‐Iron therapy is economical
compared to the alternatives.
Dosage will stay the same even over longer therapy.
There are considerably less potentially therapy‐ruining side‐effects. This is a major
problem when it comes to synthetic iron supplements. It is very common that side
effects force the therapy to be terminated and something else tried.
The last alternative when not consulting Heme‐Iron is the very expensive and
inconvenient, potentially infectious causing intravenously given iron.
By Heme‐Iron therapy with or two tablets at a single administration per day this steals
no working time. It is also convenient in other ways. There are no special precautions
over simultaneously ingested food, drink or medicine.
Heme‐Iron therapy can build up adequate iron storage in a natural and gentle fashion.
There is no change in tolerability or efficacy over longer time.
With synthetic supplements side‐effects are usually, even after initial good tolerance,
slowly accumulating until the therapy has to be discontinued.
Using Heme‐Iron very little is wasted. What is not taken up is completely inert in the
gastro‐intestinal channel as opposed to non‐adsorbed free iron ions from synthetic iron,
which are reactive and strongly irritating.
Hemoglobin iron in therapy. What do we know?

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Some published studies of heme iron supplementation. ​The following texts present and
comment some of the published scientific studies on Heme iron.
Conclusions:
‐ Heme‐Iron is better taken up than all other forms (non‐heme/synthetic) palatable iron
‐ Heme‐Iron causes significantly fewer therapy‐destroying side‐effects
‐ Heme‐Iron is safe and works well as supplement for chronics, pregnants etc.
‐ Heme‐Iron is natural in all forms of iron deficiency.
‐ Heme‐Iron can successfully replace current medications and ease on the Side‐Effects.
“For targeted prophylaxis of iron deficiency with small, side­effect­free doses,
heme­iron is thus a valuable component which increases the absorption by about
40%. Heme­iron does not cause high concentrations in the intestinal lumen of free
radical inducing, possibly harmful ferric iron.”
Comparative Absorption of Ferrous and Heme‐Iron with Meals in Normal and Iron
Deficient Subjects. Zeitschrift für Ernährungswissenschaft 1993 Mar; 32 (1): 67‐70
Ekman M, Reizenstein P. Hematology Laboratory, Karolinska Hospital and Institute,
Stockholm, Sweden.
“The study demonstrates that a low­dose iron supplement containing both heme
iron and non­heme iron (Hemofer) has fewer side effects when compared with an
equipotent, traditional non­heme iron supplement.”
Side Effects of Iron Supplements in Blood Donors: Superior Tolerance of Heme Iron.
Frykman E. J Laboratory Clinical Medicine 1994 April; 123(4): 561‐4.
“A daily dose of 27 mg elemental iron, containing a heme component, given in the
second half of pregnancy, prevents depiction of iron stores after birth in most
women. An equivalent dose of pure inorganic iron seems less effective, but the
sample size in this study was too small to demonstrate significant differences
between the two treatment groups.”
Iron Supplementation in Pregnancy: Is less enough? A randomised, placebo Controlled
Trial of Low Dose Iron Supplementation with and without Heme Iron. Eskeland B. Acta
Obstet Gynecology Scandinavia 1997 Oct 76(9);822‐828.
“Heme iron is absorbed from meat more efficiently than dietary inorganic iron
and in a different manner. Thus, iron deficiency is less frequent in countries
where meat constitutes a significant part of the diet.“
Seminars in Hematology 1998 Jan; 35 (1): 27‐34. Absorption of heme iron. Uzel C,
Conrad ME. USA Cancer Center, University of South Alabama, Mobile 36688, USA.

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CONCLUSION
The problems in practice with the therapy have mainly to do with tolerance. Getting
side‐effects in a therapy form will soon ruin it. Iron is however necessary for life and the
traditional synthetic iron forms such as Ferrous sulphate, Ferrous fumarate or similar
will bring serious side‐effects sooner or later.
Using synthetic iron therapy the only remaining alternative is inconvenient, even
painful, and costly intravenously given iron. ​There are risks with iron injections over a
longer period of time. Intravenous iron injections cause periods of exacerbation of
oxidative stress in the circulation and potentially also infections.
Safe and well tolerated ​Heme‐Iron ​does not have these problems. Both efficacy and
tolerance remain stable over longer time. Administration is the easiest possible: One
dose per day at any given time, without having to consider other medication, food or
drink. It also gives for instance chronics freedom to travel.
ADDITIONAL RESOURCES
MediTec Group AB: ​www.MediTec.se
Heme­Iron Informtation: ​www.hemeiron.com
OptiFer® Series Information:​ ​www.optifer.international
Heme­Iron E­Book: ​eBook “Heme Iron, the natural way of iron supplementation”
by Michael Collan
For more information, please contact ​FerroCare@MediTec.SE
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