Everything you need to know about heme iron Ed 2

Michael Collan

Heme IronThe natural way of iron supplementation

1 Natural heme iron has beenused largely in Scandinaviafor more than 30 years.It has no knownside-effects and toleranceis at placebo-level inclinical studies.No serious side effects orpoisonings have ever beenreported.

Heme IronThe natural way of ironsupplementation

Contents

1. Long-time use with good experiences

2. What is heme iron?

3. Two kinds of iron

4. Heme iron in use

5. Uptake and side-effects

6. Heme iron is efficient and well tolerated

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Long-time use with good experiencesBovine and porcine hemoglobin in food supplement tablets have been in use in Scandinavia since the 1970-ies. No serious side effects have ever been reported and no cases of poisoning in literally millions of users.

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. Efficacy in supplements is good and there is an extremely good record of tolerance.

Iron is an essential trace element that has important metabolic functions, including oxygen transport and storage and many redox reactions.

Insufficient intake results in the deficiency condition anaemia, adverse outcomes of pregnancy, impaired psychomotor development and cognitive performance and reduced immune function.

Section 1

Heme Iron

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The regular iron supplements today are synthetic and often produce gastrointestinal side-effects which in many cases terminate the important therapy. 

Modern women often eats a varied diet and lives healthily. Despite this iron deficiency is more common today than 50 years ago. This is mainly because women eat less in total and comparatively less heme iron.

There are two kinds of dietary iron: the inorganic iron found in vegetables and as enrichment or supplements and organic iron also known as hemoglobin or heme iron, found in meat courses. Women of today eat less meat and more vegetables and thus get less heme iron than before.

What is heme iron?Pure hemolyzed hemoglobin powder derived from the food industry as raw material for iron substitution has been of interest in Sweden since the early seventies, as this is by far the best-tolerated and efficient form of iron.

Over the years the raw material has been developed and used in a number of products.

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Today there is a new form of raw material, where iron ions are bound to natural hemoglobin to raise the iron content. This way it is now possible to have the whole theraputic dose in a tablet as purely heme iron,

There are two pathways for dietary iron. Heme iron, which is found in all meat products and heme iron supplements, is absorbed efficiently and neatly as a whole unit.

The other kind used in supplementation is non-heme iron, iron syntethically bound to a carrier and has to be broken down in the gut before the iron can be absorbed. Most of the free iron remains in the gut and causes side-effects such as constipation, diarrhea and stomach cramps. The uptake of non-heme iron is also affected by other foods consumed.

Tea, coffee, milk and eggs, for instance will ruin the absorption, but vitamin C in orange juice will help absorption of non-heme iron.

Two kinds of ironIn a normal varied diet there is around 15 mg of iron salts (non-heme) per day. 14,5 mg of this will not be absorbed. Of heme iron, which constitutes a smaller part of the diet more than a quarter will be utilized. 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 in useDr Lars-Göran Kjellin, medically responsible at the Curera clinic in Stockholm and Solna Läkarcenter  is one of many satisfied doctors who use heme iron tablets for their patients.

”This is an excellent and welcome complement to current iron preparations. Too many patients can´t handle the usual iron medications due to side-effects in the form of stomach problems.

When we put them on heme iron tablets serum iron and hemoglobin readings are corrected and they become free from symptoms. In our company care health examinations of we check women for hidden iron deficiency among other things.

This is surprisingly often the case in patients with fatigue symptoms. When they get medication blood iron levels return to normal and the patients feel better without side-effects.”

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MicronutrientsNatural bovine hemoglobin is not only well-tolerated and an efficient source of iron. It means also a wealth of micronutrients and for example amino acids and signal substances that together make the formation of blood naturally more efficient.

Called micronutrients because they are needed only in small amounts, these substances are the “magic wands” that enable the body to produce enzymes, hormones and other substances essential for proper growth and development. As tiny as the amounts are, however, the consequences of their absence are severe. Iodine, vitamin A and iron are most important in global public health terms; their lack represent a major threat to the health and development of populations the world over, particularly children and pregnant women in low-income countries. (WHO)

Micronutrients are nutrients required by humans and other organisms throughout life in small quantities to orchestrate a range of physiological functions. For people, they include dietary trace minerals in amounts generally less than 100 milligrams/day -as opposed to macrominerals which are required in larger quantities.

The microminerals or trace elements include at least iron, cobalt, chromium, copper, iodine, manganese, selenium, zinc

and molybdenum. Micronutrients also include vitamins, which are organic compounds required as nutrients in tiny amounts by an organism. (Wikipedia)

Uptake and side-effectsHeme iron is different from the iron salts also in that the hemoglobin molecule is taken in without prior reduction in the gut. The uptake itself is thus more efficient and is not affected by other simultaneously digested foodstuffs.

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In the uptake of non-heme iron there can be large differences if tea, coffee, milk or coarse bread is present. All of these affect the absorption in a negative way. A glass of orange juice makes for for more efficient absorption.

In a normal varied diet there is around 15 mg of iron salts per day. 14,5 mg will not be absorbed. Of heme iron, which constitutes a smaller part of the diet more than a quarter will be taken up.

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 efficient and welltolerated

Contents

1. Why do we need iron?

2. Dietary iron

3. The body regulates uptake

4. Women, protect yourselves against cadmium and save yourself from osteoporosis!

5. Normal Hb-value and iron deficiency at the same time?

6. Hidden iron deficiency –a problem in company health care

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Why do we need iron?Iron is an important part of the red blood cells that transport oxygen to all parts of the body. It can not be substituted with anything else. Iron is the fourth most common element in the earth crust and thought to be the main content of the earth core. Iron is also fundamental for life.

Every adult human carries about 3,5 – 4 g of iron, yet this small amount of of mineral, relative to the body weight, is essential being a key  building block in several proteins, distributed to three main compartments of the body.

The main compartment of iron in the adult human (30 mg/kg body weight) is in the circulating blood, where each mature erythrocyte carries four  heme proteins with one Fe- atom each. The oxygen carrying heme proteins are also represented in myoglobin, the protein responsible for oxygen storage and transport in muscles (4 mg Fe/kg).

A smaller but yet as important fraction of the body iron (2 mg Fe/kg) is present in various tissues as iron containing enzymes and other proteins.

Section 2

Iron absorption

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The complete list of functional iron - proteins is not yet understood, but iron is essential in electron transport proteins present in all body cells i.e cytochromes, activators of molecular oxygen (i.e peroxydases and catalases) and many others.

The third compartment of iron is the storage iron, making the body prepared for unexpected loss or changes of iron absorption.

This is a “buffer” compartment where large changes can occur between a state of iron depletion (1-2 mg/kg) and repletion without affecting the functional iron compartments. The main storage proteins are ferritin and hemosiderin.

Dietary iron The average amount of dietary ingested iron is 12 - 18 mg daily. In healthy individuals the average iron demand 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. Iron requirements should compensate for demand during growth, pregnancy and physiological and pathological losses.

In normal health iron management in the body is conservative with little or no loss of body iron save 1-2 mg being excreted, principally by sloughing of cells from the gastrointestinal tract and skin, and menstruation.

The body regulates uptake Only around ten percent of digested iron is taken up from the gut. When iron values are low, the uptake increases. If we get too much iron the uptake is blocked. In other words the body itself regulates uptake of the iron in the diet. The only exception to this is sudden large overdoses of iron. This can happen for instance when children believe iron tablets to be candy. In this case the blocking mechanism is neutralized and iron poisoning is the result. The symptoms begin with nausea and vomiting. It is the reason why non-heme iron medication always should be kept out of reach for children.

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Women, protect yourselves against cadmium and save yourself from osteoporosis!Together with lead and mercury among others cadmium is one of the heavy metals. These are extremely harmful to the human organism. ”Women who have low iron values (and especially those who smoke) are in the risk zone of getting too much cadmium.” says Marie Vahtner, professor of metal toxicology at Karolinska Institutet in Stockholm.

In a study several dietary nutritional factors were observed, among these cadmium. It was noted that in different diet groups the cadmium intake was roughly the same.

In spite of that there was a negative correlation with low iron counts and high cadmium content in the body. ”When we have low iron stores the uptake from the gut increases. Cadmium intake also increases because the mechanism for uptake is related” says Marie Vahtner.

 Until now the large group associated with cadmium has been smokers, tobacco leafs contain large amounts of cadmium and the lung uptake is greater than gut uptake. This is the reason smokers often have cadmium levels that are close to damaging.

Cadmium is stored mainly in the skeleton and once there replaces and blocks much-needed calcium uptake in the bone structure leading to osteoporosis. Therefore the risk for osteoporosis is considerable for those who have low iron counts and depleted iron stores.

Contents

1. Iron deficiency worldwide

2. What happens when iron levels are low?

3. Supplementation

4. Who needs it?

5. What is iron deficiency and who is affected?

6. Why is iron therapy problematic?

7. Learning ability for children deteriorates

8. Low iron values. Why?

9. How long does the woman bleed?

10. Normal Hb-value and iron deficiency at the same time?

11. Hidden iron deficiency –a problem in company health care

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Iron deficiency anaemia (WHO)A few salient facts

In developing countries every second pregnant woman and about 40% of preschool children are estimated to be anaemic.

In many developing countries, iron deficiency anaemia is aggravated by worm infections, malaria and other infectious diseases such as HIV and tuberculosis.

The major health consequences include poor pregnancy outcome, impaired physical and cognitive development, increased risk of morbidity in children and reduced work productivity in adults. Anaemia contributes to 20% of all maternal deaths.

The challengeIron deficiency is the most common and widespread nutritional disorder in the world. As well as affecting a large number of children and women in developing countries, it is the only nutrient deficiency which is also significantly prevalent in industralized countries.

Section 3

Iron deficiency

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The numbers are staggering: 2 billion people – over 30% of the world’s population – are anaemic, many due to iron deficiency, and in resource-poor areas, this is frequently exacerbated by infectious diseases. Malaria, HIV/AIDS, hookworm infestation, schistosomiasis, and other infections such as tuberculosis are particularly important factors contributing to the high prevalence of anaemia in some areas.

Iron deficiency affects more people than any other condition, constituting a public health condition of epidemic proportions. More subtle in its manifestations than, for example, protein-energy malnutrition, iron deficiency exacts its heaviest overall toll in terms of ill-health, premature death and lost earnings.

Iron deficiency and anaemia reduce the work capacity of individuals and entire populations, bringing serious economic consequences and obstacles to national development. Overall, it is the most vulnerable, the poorest and the least educated who are disproportionately affected by iron deficiency, and it is they who stand to gain the most by its reduction.

What happens when iron levels are low?You may get tired, have concentration problems, get bad hair and nails and feel generally weak. Low iron count has also been shown to have a negative impact on learning ability as well as physical ability. Iron status of the pregnant and thosewho plan pregnancy determines the weight of the foetus. Even to such a degree that it affects the health status of a  person during the whole lifetime. 

More than 30 % of all fertile women suffer from low iron counts due to menstrual loss of blood. Low iron counts increase the uptake of harmful cadmium, which is stored in the skeleton and causes an increasing risk for osteoporosis.

Why is this so common?Nowadays we eat smaller amounts of iron-rich meat courses  than our voracious and hard-working ancestors. We also have

a different beauty concept today with a thin body as the ideal and thus less energy-and mineral-rich food is consumed.

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SupplementationThe process of building up adequate iron stores takes months, much in the same way that depletion doesn´t happen overnight.This is why supplementary dosage usually is enough. If the dosage is higher than 50 mg 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.

Who needs it?Women, who menstruate for four days or more almost always need a supplement of iron to compensate for the blood loss.

Other risk groups are athletes, growing youngsters, the pregnant, lactating and the elderly due to either poor diet or high losses or both. Grown men rarely suffer from iron deficiency.

What is iron deficiency and who is affected?Iron carries oxygen to all cells in the body and takes part in many processes in the body. It cannot be replaced by anything else.

All iron comes from the diet and when not sufficiently present, levels will drop. Low iron counts hamper the quality of life in many ways; physical and mental performace deteriorates as well as looks. Women lose more iron due to menstruation, up to every third woman needs supplementation.

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Why is iron therapy problematic?Not complying is easy because of slow change of status (but the quality of life will be lower). Side-effects are too common and inevitably lead to therapy failure.

Not all side effects are drastic, some are merely unpleasant (but lead to quitting all the same).Too much iron can be dangerous, slow and steady supplementation in moderate doses only when needed is preferable.

Iron is an important part of the red blood cells that carry oxygen to all the cells of the body. If we don´t have enough we easily run short of breath, get tired and have problems concentrating. Our bodies contain 4-5 grammes of iron. It may be difficult to get enough of this important nutrient unless meat courses are part of the diet. Fruit, cereals and vegetables contain relatively little of useful iron.

Many of us minimize the use of meat products. At the same time we eat less than our voracious forefathers. Immobile and non-manual work makes man consume less calories and to have less of an appetite. This means that we get less iron. We also don´t use cast iron kettles for long cooking either like before.

Learning ability for children deterioratesA 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 development and cognitive performance.

Low iron values. Why? 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 than men. The symptoms of iron depletion are so common that they aren´t always recognised. Except for weakness and shortage of breath it also affects appearance. The skin grows pale and hair and nail lose strength and luster.

 

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How long does the woman bleed? Dr. Lars Ehn from Stockholm uses a simple method: ”I ask my female patients who complain of tiredness, general uneasiness and concentration problems how many days they bleed during menstruation. If they answer four or more I´m pretty sure that they need iron supplementation. In reality no-one can replenish such losses with normal diet alone.”

Of course the diagnosis should be confirmed with a Hb- and serum ferritin level test. Today ferritin, which gives an indication of reserve iron stores is usually taken. This was not always the case. In earlier times the Hb would suffice, instead of taking a deeper approach.

Normal Hb-value and iron deficiency at the same time?An ordinary Hb-test says nothing about stored iron. The iron stores of the body are measurable with a so-called serum ferritin count. When serum ferritin lies above 30 ug/l the iron stores are full. If this value drops the uptake from the gut will increase.

In a comparative study vegetarians had lower serum ferritin levels, but comparative Hb-levels as omnivores. This was because the Hb-levels don´t start to drop before the reserves are running out.

”You have to remember that general symptoms start to occur only when reserves are empty and the Hb-levels drop drastically. That´s why it´s very important to check serum ferritin levels as well.” says Dr Lars Ehn. This is a question for workplace health care mainly. If and when a hard-working woman gets fatigued from iron deficiency without being aware  of it the results can be quite serious. Stress and burn-outs all too common these days.

 

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Hidden iron deficiency - a problem in company health care Iron deficiency can give the following symptoms:

# •# Tiredness, fatigue, passivity and drowsiness

# •# Concentration difficulties and increased need of sleep

# •# Impaired performance

# •# Lessened learning ability

 Research for preventing iron depletion anemia has been going on since the 1960:ies, mainly focusing on blood-donors and the pregnant. One of the pioneers is Dr. Lars Ehn. He has shown that heme iron preparations are more safe and efficient than traditional high-dose iron tablets. He is one of those who have developed new iron preparations through studies.

”I have a number of patients that have taken heme iron preparations for years. They have kept a satisfactory iron balance without the unfortunately all-too-common side effects that are often assocated with iron preparations”. Today he works in the company health care sector where there are a large number of iron deficient female patients. Many have a

hidden iron defiency i.e. normal Hb but very small or no body iron reserves. This especially if she bleeds more than three days in menstruation. The iron depots are tested by measuring serum ferritin levels.

2 There are several groups with a special interest in iron and supplementation

Groups

Contents

1. High prevalence of low iron counts

2. Menstruation

3. Low iron counts

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High prevalence of low iron countsOver 30% of all fertile women worldwide (even higher prevalence among teenagers and in the developing countries), especially those with menstruation for more than three days, have a latent anemia with increased uptake of cadmium instead of iron.

Iron deficiency is the most common explanation for anemia in women of childbearing age, but the causes vary. Blood loss and pregnancy or lack of meat in the diet are the leading causes of

Section 1

Fertile females

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iron deficiency in women. Other more rare reasons include problems of absorption (acquired or inherited), nutritional deficiencies (iron, B12, folate, zinc); or disease (fibroids, cancer, inherited anemias or bleeding disorders)

Heavy menstruation and childbirth are significant sources of blood loss for women of childbearing age. Chronic blood loss can also be due to endometriosis or fibroids, which require a great amount of blood. Fibroids are usually benign, but can grow to the size of a baseball or grapefruit before they are detected. Fibroids of the uterus can interfere with delivery during childbirth, requiring Cesarean-section delivery. von Willibrand disease is another overlooked cause of heavy menstrual bleeding in women.

Menstruation and blood lossThe average menstrual period lasts anywhere from two to five days. Blood loss during this time is estimated to be as little as one ounce—a light or average period—and as much as 1 cup—a heavy period.

The amount of blood lost during childbirth is about 500cc (about a pint) or approximately two cups of blood. Thereby 200–250 milligrams of iron is lost. In addition, the iron contained in the

newborn baby’s blood and tissues contain another 500-800 milligrams of iron which originally came from the mother.

A woman’s natural iron regulatory system takes care to increase absorption of iron from her diet during these times of blood loss. Her normal absorption rate of 1 milligram is stepped up to 1.5–3 milligrams per day—the female body’s natural response to blood loss.

Heavy blood loss during menstruation (menorrhagia) is called abnormal uterine bleeding (AUB). According to the National Women’s Health Resource Center Hotline, AUB is one of the most common reasons women contact them.

Prolonged heavy bleeding (hypermenorrhea), where the duration might be as long as two weeks or irregular bleeding (metrorrhagia) may eventually lead to anemia if the loss is not offset with increased iron intake.

Acute blood loss can also happen as a result of trauma or surgery, as a result of taking aspirin or certain medications, especially those used to relieve arthritic pain, and abusing alcohol. Another cause of blood loss is esophageal bleeding in a condition called Mallory-Weiss syndrome. In Mallory-Weiss, the lining of the esophagus is torn, usually from repeated vomiting, which can be seen in females who are bulimic.

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Low iron countsCadmium has an increased uptake in situations with low iron counts and replaces calcium in bones thus increasing the risk for osteoporosis later in life. In addition, latent iron deficiency and subacute anaemia have many well-documented negative effects. For example, decreasing the prospective mother's quality of life considerably and may even lead to lifelong impact on the baby.  

Growing young with low iron values could permanently suffer from neural development damage and reduced learning ability.

We are dealing with a society- and individe related problem on a large scale when it comes to female iron deficiency due to menstruational bleeding. The World Health Organisation, WHO regards anaemias and related conditions the second largest health problem after infections.

Iron deficiency is a common problem, especially for women, so common, in fact, that 5% of women between the ages of 20 and 49 have iron deficiency with anemia and 11% have iron deficiency without anemia

Contents

1. Risk factor due to maternal deficiency

2. Life-long effects

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Risk factor due to maternal deficiency

Low birth weight is a risk factor for coronary heart disease, diabetes, stroke and hypertension. Depression is highly associated with these conditions.

Section 2

Maternal iron deficiency

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Studies in Great Britain have shown that people who had low birth weight were at increased risk of coronary heart disease and the disorders related to it: stroke, non-insulin dependent diabetes, raised blood pressure, and the metabolic syndrome.

In a study of 16 000 men and women born in Hertfordshire death rates from coronary heart disease fell twofold between those at the lower and upper ends of the birth weight distribution.

In groups investigated clinically the prevalence of non-insulin dependent diabetes and impaired glucose tolerance fell threefold. Such findings led to the "fetal origins hypothesis", which states that cardiovascular disease and non-insulin dependent diabetes originate through adaptations that the fetus makes when it is undernourished. These adaptations, which include slowing of growth, permanently change the structure and function of the body.

 

Life-long effectsLow birthweight, thinness and short body length at birth are now known to be associated with increased rates of cardiovascular disease and non-insulin dependent diabetes in adult life. The fetal origins hypothesis proposes that these diseases originate through adaptations which the fetus makes

when it is undernourished. These adaptations may be cardiovascular, metabolic or endocrine. They permanently change the structure and function of the body. Prevention of the diseases may depend on prevention of imbalances in fetal growth or imbalances between prenatal and postnatal growth, or imbalances in nutrient supply to the fetus.

 Anaemia and iron deficiency during pregnancy are associated with large placental weight and a high ratio of placental weight to birthweight. This points to maternal nutritional deficiency as a cause for discordance between placental and fetal growth. This may have important implications for the prevention of adult hypertension, which appears to have its origin in fetal life.

 If the growth of a female fetus is constrained by lack of nutrients, there are persisting changes in her physiology and metabolism which lead to reduced fetal growth and raised blood pressure in the next generation. Public health policies to improve fetal growth in one generation may therefore benefit succeeding generations as well.

Children who have iron-deficiency anemia in infancy are at risk for long-lasting developmental disadvantage as compared with their peers with better iron status.

Contents

1. Anaemia in pregnancy

2. Iron deficiency and anaemia

3. Folic acid and pregnancy

4. Nutritional status and birth weight

5. Effects on the fetus and infant

6. Effects on pregnancy outcome

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Anaemia in pregnancy

Iron deficiency is the most common deficiency state in the world, affecting more than 2 billion people globally. Although it is particularly prevalent in less-developed countries, it remains a significant problem in the developed world, even where other forms of malnutrition have already been almost eliminated. Effective management is needed to prevent adverse maternal and pregnancy outcomes, including the need for red cell transfusion. 

Section 3

Anaemia in pregnancy

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Anaemia is defined by Hb < 110g/l in first trimester, < 105g/l in second and third trimesters and < 100g/l in the postpartum period. For anaemic women, a trial of oral iron should be considered as the first line diagnostic test, whereby an increment demonstrated at two weeks is a positive result.

Once Hb is in the normal range supplementation should continue for three months and at least until 6 weeks postpartum to replenish iron stores.

Iron deficiency and anaemiaIron deficiency represents a spectrum ranging from iron depletion to iron deficiency anaemia. In iron depletion, the amount of stored iron (measured by serum ferritin concentration) is reduced but the amount of transport and functional iron may not be affected. 

Those with iron depletion have no iron stores to mobilize if the body requires additional iron. In iron-deficient erythropoiesis, stored iron is depleted and transport iron (measured by transferrin saturation) is reduced further; the amount of iron absorbed is not sufficient to replace the amount lost or to provide the amount needed for growth and function. In this

stage, the shortage of iron limits red blood cell production and results in increased erthryocyte protoporphyrin concentration. 

In iron-deficiency anaemia, the most severe form of iron deficiency, there is shortage of iron stores, transport and functional iron, resulting in reduced Hb in addition to low serum ferritin, low transferrin saturation and increased erythrocyte protoporphyrin concentration.

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Folic acid and pregnancy26-year old Lena was pregnant well into the first trimester. Everything was looking good when the sudden bad news hit. The doctor told her that the foetus had a serious birth defect in the form of spinal injury and that now they had to decide whether to keep the baby or terminate the pregnancy. How could this happen? Lena thought she had done well by taking

the prescribed medication of iron and folic acid supplements as soon as pregnancy was confirmed.

Modern medicine has concluded that an integral part of the central nervous system in the foetus develops during a stage at when the mother might not be aware of that she is pregnant. The so-called neural tube evolution is hampered by a lack of folic acid in the mother. The risk of birth defect is then high. If the baby is born with spinal defect it will be crippled for life.

Folic acid has been shown to reduce birth defects when taken during the initial stages of prenatal development. The risk of birth defects decreases significantly with a supplementation of folic acid. If pregnancy is possible it is crucial that folate levels are satisfactory, since otherwise it may be too late. The probability is relatively low, but not negligible.

 

How much folic acid is needed?The RDA recommendation before and during pregnancy is 800 µg per day and 400 µg normally for men and women. The normal intake is between 200 and 400 µg per day. Folic acid is needed for the cell genesis and during growth of the foetus. Folic acid is also believed to lower the risk of heart infarct. It is also believed that lack of folic acid may cause malignant cell changes in the uterus and sphincter.

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Nutritional status and birth weightIn English studies it has been shown 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. How is this possible? Professor David Barkers epidemological research sheds new light on the subject.

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 turned out that those born by mothers with low nutritional status suffered from various internal diseases such as low blood pressure, heart disorders and diabetes to a higher degree.

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.

It´s been said that even if the mother has low iron counts the baby will get what it needs. Then the symptoms would only

concern the mother. Now we know better. New research shows that low iron counts on the mother has a lifelong impact on the baby´s health.

Do hereditary factors matter?We know today that every third woman has too low iron counts. Body iron storage is on a 75 percent level. Those who have a tendency to bleed much often have the same problem in earlier generations as well, since low iron counts are often inherited. One might answer yes to the question: Are your bleedings normal? Menstruation bleedings are perceived as normal since they don´t vary from time to time. Which they are, of course, for the particular person. The difference being that some bleed normally for two days, other for four days.

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Effects on the fetus and infantThe fetus is relatively protected from the effects of iron deficiency by upregulation of placental iron transport proteins (Gambling et al, 2001) but evidence suggests that maternal iron depletion increases the risk of iron deficiency in the first 3 months of life, by a variety of mechanisms (Puolakka et al, 1980, Colomer et al, 1990). 

Impaired psychomotor and/ or mental development are well described in infants with iron deficiency anaemia and may also negatively contribute to infant and social emotional behaviour (Perez et al, 2005) and have an association with adult onset

diseases, although this is a controversial area (Beard et al, 2008; Insel et al, 2008).

Effects on pregnancy outcomeThere is some evidence for the association between maternal iron deficiency and preterm delivery, (Scholl et al, 1994), low birth weight (Cogswell et al, 2003), possibly placental abruption and increased peripartum blood loss (Arnold et al, 2009).

However further research on the effect of iron deficiency, independent of confounding factors, is necessary to establish a clear causal relationship with pregnancy and fetal outcomes.

(UK guidelines on the management of iron deficiency in pregnancy, British Committee for Standards in Haematology.)

Contents

1. Non-heme iron not absorbed when using Omeprazole

2. Heme iron works in achlorhydria

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Non-heme 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.

Section 4

Gastric acid

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Omeprazole is a potent gastric acid suppressant that works by inhibiting the mucosal proton pump 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.

Omeprazole and possibly all proton pump inhibitors decrease the absorption of oral iron supplementation. Iron-deficient patients taking proton pump inhibitors may have to be treated with high dose iron therapy for a longer duration or with intravenous iron therapy. Omeprazole is an acid-reducer that is used to treat acid reflux and stomach ulcers.

Omeprazole works by preventing acid pumping cells found on the stomach wall from producing acid. Lack of enough 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.

Heme iron works in achlorhydriaUnlike heme iron, nonheme iron depends on a low gastric pH to form soluble bivalent ferrous iron for absorption in the duodenum. Unless it is converted to this state, it cannot be absorbed. Although the heme component is absorbed independent of gastric pH, the non-heme part requires an acidic pH for absorption

Contents

1. Post-operative anaemia is not unusual

2. Signs and Symptoms

3. Oral iron supplementation is often not effective

4. Heme iron good for maintenance treatment

 

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Post-operative anaemia is not unusual

It is not unusual for anemia to be present following surgery, however it may or may not be considered a complication of surgery. A certain amount of blood loss is expected during surgery and can vary depending on the procedure.

All patients require care and observation following surgery. The physician’s documentation should indicate the presence of blood loss anemia and that treatment and/or additional monitoring was required..

Section 5

Post-operative anaemia

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Signs and Symptoms(It is important to consider the age and size of the patient when reviewing signs and symptoms)

- Low hemoglobin/hematocrit, faintness, dizziness, thirst,

- Sweating, weak/rapid pulse, rapid respiratory rate,

- Orthostatic hypotension, paleness, decreased blood pressure, fatigue, shortness of breath.

Anemia can affect how patients respond to surgery and how quickly they return to health. Unfortunately, testing for anemia is often not a top priority during the preoperative period. Anemia is often one of the easiest conditions to diagnose and to treat when it is recognized early enough before surgery.

Anemia is commonly unrecognized and overlooked by physicians and surgeons because it often exhibits very non-specific symptoms or no symptoms at all.The causes of preoperative anemia are multifactorial and may include acute or chronic blood loss, poor nutrition, renal insufficiency, malignancy or chronic disease.

Untreated bleeding episodes, along with the frequent phlebotomies that are a standard part of postoperative

procedure, cause blood loss and can contribute to anemia during surgery and recovery. Postoperative inflammatory response can additionally lead to blunted erythropoietic response and diminished iron availability, resulting in anemia.

Patients who are transfused after surgery as a result of anemia are more likely to develop postoperative infection, require longer periods of mechanical ventilation, and have a greater risk of mortality.

Anaemia is common after major surgery and seems easily explained by blood loss during and after surgery. Moreover, therapy is simple: either transfusions with red cells are given or iron tablets are prescribed. Although the clinical use of blood transfusion has opened new perspectives in surgery, transfusions are associated with risks that can cause morbidity and mortality. 

The characteristics of iron metabolism in plain iron deficiency anaemia and phlebotomized healthy individuals are a reduced serum iron and ferritin concentration, reduced transferrin saturation, increased serum transferrin concentration and increased transferrin receptor concentration.

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Oral iron supplementation is often not effectiveGiven the fact that a functional iron deficiency exists postoperatively, it is noteworthy that oral iron supplementation is often not effective to increase postoperative haemoglobin levels. Iron bound to transferrin ex vivo, and given intravenously is rapidly and almost completely consumed by red cells during the first week after surgery, as shown by ferrokinetic measurements.

Not only iron (and vitamin B12 and folic acid) is necessary for an appropriate production or red cells but also EPO is required for the stimulation of erythropiesis. In the postoperative phase, a short period of relative erythropoietin (EPO) deficiency is found up to the fourth day after surgery.

Postoperative anaemia may be considered an acute variant of the anaemia of chronic disease due to the inflammatory effect of the procedure. This inflammatory effect exerts its influence on erythropoiesis through a disturbance of iron metabolism, inducing functional iron deficiency and through a blunted erythropoietin response and these findings may have implications for its treatment.

Would post-operation patients receive any benefit from higher hemoglobin levels? A study published by Lawrence et al. in

2003 said, “They do.” Two major benefits were observed in post-op orthopedic patients. One is better functional status: they seem to walk better! It was felt that a patient’s ability to walk without assistance 60 days post-operation correlated with success of surgery and survival. Secondly, patients seemed to have higher efficacy of rehabilitation. For example, they have shorter length of stay.

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Anemia is an important concern for the surgical patient throughout the entire surgical process, including the preoperative period, the surgery itself, as well as the postoperative recovery period. It is estimated that one-third to one-half of surgical patients may be anemic preoperatively secondary to the conditions for which they require surgery. After surgery, anemia is even more common, affecting 90% of patients.

Heme iron is good for maintenance treatmentDue to excellent long-term tolerance, price, ease of use and good efficacy heme iron is especially effective in maintenance treatment.

Contents

1. Chronic diseases often connected to anaemia

2. Why intravenous iron isn't always good

3. Therapy over long time

33

Chronic diseases often connected to anaemiaThere is a large number of chronics in various diseases with anaemia. These are for instance Chronic kidney disease, Inflamatory bowel disease or Coronary heart disease patients and many others.

Section 6

Chronic diseases

34

Why intravenous iron isn't always goodChronics usually receive regular syntethic oral non-heme tablets with 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 perod of time: overdosing and increased oxidative stress

Intravenous iron injections have been shown to be effective, the iron depots in the body are secured and blood genesis is more effective. Side-effects in conjunction with the injections are few but serious allergic reactions may appear.

There are however risks with iron injections over a longer period of time. Intravenous iron injections cause periods of exacerbation of oxidative stress in the circulation.

Additionally the iron content in the body is often too high, which is associated with chronic inflammation and vascular damage. This is especially worrying since it is known that patients with e.g CKD have increased oxidative stress, chronic

low-level inflammation and serious vascular disease.

This is considered part of the exlanation as to why CKD patients often die prematurely because of cardiovascular disease.

Therapy over long timeTolerance for heme iron is equal or close to placebo. There is no change in tolerance over time.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. 

It also makes for easy self-medication and freedom to travel.

Contents

1. Effect of supplementation on blood donors.

2. Why heme iron?

3. Is heme iron enough?

35

Effect of supplementation on blood donors.

Since blood donation is voluntary and this is a free service for the fellow man it´s natural to ”guard the sources”. This means that blood donors should receive iron supplementation to

Section 7

Blood donation

36

compensate for iron loss from the blood donated, especially if low values are detected.

This has not always been the case because of low efficacy and frequent side-effects from the non-heme iron given.

Why heme iron?The heme and non-heme forms of iron are absorbed by different mechanisms. The usual non-heme iron remedies, such as ferrous sulphate, produce unwanted side-effects in the form of constipation, stomach pains or diarrhea. This often leads 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. Having low iron counts in between also diminishes the donors´ Quality of Life.

There are many negative factors influencing non-heme iron absorption itself. Among these are intake of tannins in tea and coffee. Phytates in unleavened whole grain bread, milk proteins, albumin and soy proteins may also reduce absorption. This means that a regular diet and non-heme supplements may not be enough to compensate fo iron loss.

Is heme iron enough?Non-heme 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 donation absorption of non-heme iron practically ceases for  around four days.

30 days of supplementation with 100 mg Fe++ non-heme iron at a bio-availablity of 2  % theoretically gives 60 mg absorbed iron. At 5 %, which is unusual, the amount is 150 mg. From there on this drops depending on the factors mentioned before.

Over the long run there is also an inflation in non-heme iron absorption due to a numbing of the mucosa and a constant uneasy feeling with gastric disturbancies (not all side-effects lead to quick termination). This is because in order for non-heme iron to be absorbed it has to split from its carrier in the acidic environment of the stomach. The uptake is low and this will leave free iron ions in the gut. These in themselves are highly reactive, and considered toxic to the organism.

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Supplementation with 18 mg of heme iron for thirty days with a bio-availability of 20 % gives 108 mg of absorbed iron. Heme iron is very well tolerated and is known to have a side-effects ratio as placebo. This means a higher therapy success rate.

This is why heme iron tablets with a dose of 18 mg Fe++ can compete with non-heme preparations of 100 mg Fe++ or more.

Heme iron will also not block the uptake of zinc as non-heme iron in doses over 60 mg will.

Contents

1. Optimal iron status important

2. Sports anaemia

3. Why heme iron?

38

Optimal iron status important

Most athletes know that iron is a mineral required for the formation of the red blood cells used to transport oxygen to hardworking muscles, and that insufficiency of iron causes anaemia, characterized by fatigue, listlessness and a general lack of energy.

Because of this, they also know that maintaining iron status and checking red blood cell or hemoglobin (Hb)-levels is vital for performance.

Basically, iron difficulties can take two forms, either iron deficiency or true anaemia. Iron deficiency itself has two distinct stages. Stage 1, the iron-depletion stage, is characterized by blood-ferritin levels of less than 12 µg/ml, which indicates that iron levels have been significantly reduced.

Section 8

Athletes

39

Ferritin, a key protein which latches onto iron, serves as an important mechanism for iron storage within the body. Stage 2 of iron deficiency involves iron-deficient erythropoiesis, which basically means that newly created red blood cells contain lower than normal amounts of iron.

The human body contains approximately 3–5 g of iron. The daily loss of 1–2 mg is replaced by dietary iron (8 mg/day for adult men, and 18 mg/day for adult women) absorbed within the small intestine by duodenal enterocytes.

If the iron status becomes severely depleted (through inadequate intake, poor absorption or iron losses), blood haemoglobin levels will drop, leading to a reduction in the oxygen carrying capacity. The result is fatigue, tiredness and breathlessness, even after gentle exertion – the classic signs of anaemia.

 

Sports anaemiaAthletes in heavy training are at risk due to the so-called sports anaemia. This is more is more pronounced for women due to the monthly loss of blood in menstruation. It is also common for athletes to eat and drink more "empty calories," which for a

young growing body of increasing muscle mass and blood volume might be a problem with the performance and fatigue as a result. However, haemolysis is due primarily to impact forces resulting from foot-strike.

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Haemolysis is the breakdown and destruction of red blood cells caused by the physical pounding action of running, leading to the release and loss of iron. In the past, the age-old hemoglobin test was thought to be sufficient to determine an athlete’s iron status, the ‘normal’ range being 12-16 g/dl (grams per decilitre), with anything under 12g/dl signifying iron anaemia.

However, more recent research has indicated that you can be quite iron deficient without being diagnosed as anaemic. This is because reduced blood haemoglobin is one of the very final stages in iron deficiency, and a lot of iron-dependent systems can suffer before this final stage is detectable.

Iron depletion is a continuous process that ultimately results in iron deficiency anaemia if untreated. Iron deficiency anaemia is a condition where iron is depleted to such an extent that the manufacture of haemoglobin and red blood cells is limited.

About 30 per cent of adult women and 40 per cent of adolescent women are iron deficient, while around 6 per cent of both groups suffer from true iron-deficiency anaemia. However, studies of athletes report higher frequencies of iron problems; research indicates that up to 19 per cent of swimmers and runners may be troubled by iron-deficiency anaemia, which can have a strongly negative impact on performance.

Iron problems can have a big impact on performance. Anaemia, by reducing the oxygen carrying capacity of the blood, can eat away at maximal aerobic capacity (V02max), lower endurance, and increase fatigue.

Technically, anaemia is present if hemoglobin levels fall below 12 g/dl or if haematocrit plunges below 36 per cent. However, remember that 'normal' readings for these two variables may in fact not be normal. A female athlete with a haematocrit of 37 per cent is in the normal range, for example, but if her usual haematocrit is 42, she would actually be mildly anaemic, and her athletic performances would suffer.

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Why heme iron?Equally important to efficacy is good tolerance. Stomach problems can be fateful for a serious athlete.

Heme iron in contrast to syntethic iron is taken up around four times more efficiently and contain a natural balance of miniscule trace elements and other components that are essential to red cell production and general functions of the body.

Maintaining an optimum iron status could be far more important for athletes than has previously been realised, especially given that even a mild shortfall appears to not only reduce maximum oxygen uptake capacity and aerobic efficiency but also to reduce the body’s response to aerobic training.

3 Most frequently asked questions about iron and iron deficiencyNotes

FAQ & Notes

Contents

1. Why are low iron levels so common?

2. What happens when the iron levels are low?

3. What forms of digestible iron is there?

4. How is the iron stored in the body?

5. What affects the uptake?

6. Can you get too much iron?

7. I understand that the source for heme iron is bovine blood from the food industry. What about BSE and such?

8. How safe is heme iron?

9. I heard heme iron could be carcinogenic?43

Why are low iron levels so common?

Mainly because we nowadays eat less of a diet that contains less of iron-rich meat courses than our voracious and hard-working ancestors.

We also have a different beauty concept today with a thin body as the ideal and thus less energy- and mineral-rich food is consumed. Women who menstruate for three days or more therefore almost always need a supplement of iron to compensate for the blood loss.

Other risk groups are athletes, growing youngsters, the pregnant and lactating. Grown men rarely suffer from iron deficiency.

What happens when the iron levels are low?You may get tired, have concentration problems, bad hair and nails and feel generally weak.

Low iron count has also been shown to have a negative impact on the learning ability as well as the physical ability. Iron status

Section 1

Frequently asked questions

44

of the pregnant and those who plan pregnancy has an effect on the weight of the foetus. Even to such a degree that it affects the health status of a person during the whole lifetime. Also the uptake of cadmium is increased, which may lead to osteoporosis.

What forms of digestible iron is there?The elemental iron is called organic or heme iron when it is bound to the proteins hemoglobin or myoglobin, as is the case in meat courses.

All other forms of iron are inorganic or non-heme and this is when the iron molecule is chelated or bound to for instance salts (as in vegetables) starch, citrates or other chemical compounds.

 

How is the iron stored in the body?In a blood test the Hb-value tells how much iron the body has available for transporting oxygen to the cells. The ferritin count is used to measure stored iron. Iron is also used for muscle growth and in enzymes.

 What affects the uptake?Coffee, tea, milk and whole-grain bread have a lessening effect on iron uptake, while vitamin C, for instance in orange juice has a positive effect.

The heme iron in meat courses is being absorbed through a separate mechanism and is practically uninfluenced by what is eaten at the same time. The calcium in milk products is however regarded as having a generally lessening effect on iron uptake.

 

Can you get too much iron?Yes, if you suffer from the rare and hereditary disease of hemochromatose or if you suddenly are exposed to huge doses.

The poisoning dose is considered to be 20 mg or more per kilo of body weight. The result is primarily nausea, but it may also be dangerous. This is the reason that iron supplements should always be kept out of reach for children.

Normally the body regulates automatically the iron uptake so that too much is not absorbed.

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From heme iron only what is needed is absorbed. The rest remains inert in the gut, as opposed to non-heme iron, which leaves the not-absorbed part as toxic and reactive free iron ions in the stomach causing gastro-intestinal side-effects.. The efficacy of heme iron is so good, that a small dose is all that’s needed for iron replacement.

I understand that the source for heme iron is bovine blood from the food industry. What about BSE and such?There is no BSE within the EU any longer and certification is very strict. Today this is not even theoretically a problem.

How safe is heme iron?There have never been any serious side-effects or poisonings reported even after massive use since the 1970’ies. In clinical studies the ratio of side-effects is placebo level (lowest possible). It is unlikely for poisoning to occur with the low doses in heme iron tablets. Today the raw material has evolved and non-heme iron addition is not needed any more.

I heard heme iron could be carcinogenic?No, it can not. Why you may see this confusion is because heme sometimes is used as a measure of meat consumption and as anyone understands that consuming a lot of meat in different forms and everything that goes with it has health issues. Especially for meat that is prepared with nitrate salts, additives, spices, fat and flavors etc. that are often proven harmful to the human and even carcinogenous.

Heme iron is by definition the form of iron that is naturally bound to hemoglobin and myoglobin. It is the most important form of dietary iron, very efficient, has no known side-effects and is not carcinogenous.

The natural heme iron in the OptiFer® series of supplements has only good health implications, is very effective and is side-effect free in recommended doses.

Contents

1. Acknowledgements

2. About the author

46

Acknowledgements

Images are courtesy of FreeDigitalPhotos.net.

Thanks to Leila País de Miranda for assistance in correcture.

About the authorMichael Collan is a marketing manager with an academic exam in Business. The experience lies mainly with the marketing of pharmaceuticals. He’s outwards and communicative, good at administering and managing projects and information, establishing and working contacts.

Since graduation he has worked as product specialist for Roche in Finland within general practice and rheumatology. After this as product manager for DCG Nordic AB, a subsidiary of Biologische Heilmittel Heel GmbH since 1994. Subsequenly at Cryoguard Sweden AB as Marketing Manager for heme iron supplement tablets.

The academic degree is Ekonomie magister (Bachelor) of Business Administration. There is also an examination as registered product specialist in pharmacology and medicine.

Section 2

Notes

47

Today Michael works at marketing manager for MediTec FerroCare Division OptiFer® Series and is also making documentaries, SlideShares and clips of the products, on heme iron, why and how it works so well."

Websites are

www.optifer.international and www.hemeiron.com.