Iron therapy - without problems whitepaper text

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 can 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.

The present situation

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.

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.

This is why women need more iron intake on a regular basis 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
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.

Importance of iron supplementation

Many iron supplementation treatments fail because synthetic non-heme iron often 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 gastrointestinal 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.

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, such as overdosing and increased oxidative stress.

The 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 psychomotor and cognitive development plus further cognitive performance in life.

Non-heme/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 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 multifactorial. Hemodilution, absolute or functional iron deficiency, activation of the inflammatory cascade, and impaired erythropoietin production and activity are some pathophysiological 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 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.

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

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.

Anemia and inflammatory diseases

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.

Inflammatory diseases that can lead to anemia include rheumatoid arthritis, which causes pain, swelling, stiffness, loss of function in the joints, and 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/)

Another factor is that phytates in müsli, whole grain bread, milk proteins, albumin and soy proteins may complex-bind iron and thus reduce absorption.

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.

Nutritional status and birth weight

English Professor David Barker's epidemiological 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 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.

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.

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 non-heme 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, 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 and tolerance 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.

Heme iron is very well tolerated

There are no known unpleasant side-effects. Uptake or tolerance will not change over time.

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 side-effects with heme-iron

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.


All regular supplements are synthetic. They feature chemically bonded iron.

Heme iron supplements are made with natural bovine hemoglobin.


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 infection-causing intravenously given iron.

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 gastrointestinal channel as opposed to non-adsorbed free iron ions from synthetic iron, which are reactive and strongly irritating.

Some published studies of heme iron supplementation

The following texts present and comment some of the published scientific studies on heme iron.


  • 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.
Comparative Absorption, Ekman M, Reizenstein P

“For targeted prophylaxis of iron deficiency with small, side-effect-free doses, heme iron is thus a valuable component which increases the absorption by about 40%. Heme-iron 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.

Side Effects of Iron Supplements, Frykman E. J

“The study demonstrates that a low-dose iron supplement containing both heme iron and non-heme iron (Hemofer) has fewer side effects when compared with an equipotent, traditional non-heme 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.

Iron supplementation in pregnancy. Eskeland B

“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.

Absorption of heme iron, Uzel C, Conrad ME

“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.


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.

Created By
Michael Collan MediTec Group


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