In this article you will learn why too much iron can lead to infertility, inflammation and impaired sugar metabolism.
And why at the same time too little iron is the reason why you are tired, weak and depressed.
Preface:
Everything in nature has two sides. Plus and minus. The golden mean lies between black and white!
We humans tend to extremes:
the more the better or the bigger the better. We should remember that everything is a balance between too little and too much.
In addition, every person is different. This is due to our genetic blueprint, which determines the structure and functioning of our organism.
This blueprint contains thousands of genes.
But still this blueprint is different in each of us. This is called genetic polymorphism.
Although we may all have the transporter for iron in the intestine, the expression is different in each of us. In human 1 it is highly regulated, in human 2 it is normal and in human 3 it is almost completely absent. We have to take all this into account.
Is that understandable?
Even if we all have the same gene, the functionality of this gene is very differently expressed! On the one hand because this gene can be mutated, on the other hand changed by so-called epigenetic influences. But there are simply different versions of a gene. Just like there are different shades of colors.
That’s why we can’t make a general judgment and say everyone needs this or that.
Everything is individual. The most important advisor is your own body feeling. In addition, it is important to know some basics:
Worldwide, almost two billion people are affected by iron deficiency.
The human body consists of approximately 2-6 grams of iron.
On average, we take in about 10 milligrams through our food, but we only absorb a fraction of it! 1-2mg we lose again.
So it is a balance!!!
Why is this important? Because then you know what ratios we are talking about.
If you have an iron deficiency, a tablet with 5mg of iron is useless, because only a fraction of it is absorbed!
But I also know that if I take 100mg of iron tablets a day for weeks, I will probably overload myself with it soon!
Men have about 50 milligrams of iron per kilogram of body weight,
Women about 38 milligrams per kilogram of body weight.
The more body weight, the more iron.
Iron has two functions in the body: oxygen transport , electron transport.
The special feature of iron is to be able to bind oxygen.
Iron is a component of the heme molecule. Hems are compounds with an iron ion as the central atom surrounded by porphyrin molecules.
The heme molecule serves as the most important transport and storage medium for oxygen in all mammals, including humans.
Iron means oxygen. Without oxygen, we suffocate. Without oxygen, our aerobic energy production collapses and we rely on lactic acid fermentation.
Heme Iron.
Iron bound to heme supplies all our organs heart, brain, kidneys, intestine …. with oxygen.
Iron is stored in the body as ferritin. A storage protein.
Iron is transported in the body to transferrin. A transport protein.
Iron is regulated in the body by hepcidin. A regulatory protein.
About 10% of the iron ingested with food is absorbed.
This value varies depending on the situation and the type of food. Iron from meat is absorbed much better than iron from plants because there are specific transporters for heme iron. Iron can be absorbed most efficiently as heme iron (meat, blood).
Heme iron does not exist in plants. Only ferritic iron and organic complexed iron exist in plants.
Plants contain additional substances called complexing agents to protect themselves from predators, for example phytic acid. Phytic acid binds various minerals and makes them unabsorbable for the body. Tea also contains such complexing agents.
Important: Phytic acid is not bad per se ! It also binds many toxins and has been shown to lower the risk of colon cancer! Everything depends on the context.
The simultaneous availability of vitamin C /ascorbic acid promotes the absorption of especially plant iron, as it reduces the 3-valent iron to 2-valent iron. There are other mechanisms of reduction besides vitamin C: gastric acid and intestinal enzymes. Protein and citrate also increase absorption!
Iron in milk or breast milk is also much more available in the form of lactoferrin!
Example:
100g beef liver contains about 7 milligrams of iron. This is mainly heme – iron Fe2+.
100g pumpkin seeds contain about 5 milligrams of iron. This is mainly non-heme iron Fe3+.
Officially, both provide good iron. But this is deceptive!
Who calculates his daily intake on the basis of theoretical nutrition tables is wrong!
Because the actual amount in the food varies and the type of food also determines the absorption into the body !
Meat provides the same heme molecule that we humans use.
Because both originate from mammalian cells.
Heme synthesis is very complex and very susceptible to interference. Again, gene polymorphisms may interfere with production. In the case of very severe disorders, we speak of porphyrias.
If we take heme directly from meat, we spare our body the complex self-synthesis!
A plant cell uses iron differently and it is therefore understandable that plant iron is more difficult to utilize than animal iron.
So we save ourselves the extremely complex process of heme synthesis when we eat meat directly.
The small intestine cells preferentially absorb Fe2+, but can also absorb Fe3+. ( Details see below )
Pumpkin seeds primarily provide the much less usable 3-valent iron (non-heme iron). For comparison, heme iron is absorbed at an average rate of 20-30%, while non-heme iron is absorbed at only 1-10%.
So it is not so easy to calculate one’s iron requirement and iron intake.
Theory and practice are far apart!
This is because the iron and also that of all other micronutrients in food varies greatly and the intake also varies.
And what a food contains theoretically and what it really contains is also something.
Keyword storage, transport, feeding, fertilizer, cooking.
Vegetarians are often deficient in iron.
Pregnancy, bleeding, great efforts increase the need for iron !
With food intolerances ( celiac disease ) and chronic inflammatory bowel diseases a lot of iron is lost!
It is interesting to note that many people have gone through a „genetic bottleneck“ in the last generations: due to agriculture and sedentarism in the last 10,000 years, many genetic alleles have become more dominant, which help to cope better with an agricultural, often vegetarian diet! The ancient hunter-gatherer genes have been partially displaced in some.
As stated, there are different versions of a gene for each body structure.
The same transporter , the same protein , the same receptor can be version A or B . We are talking about the slightest changes due to mutations. Smallest deletions or insertions!
For specialists:
There are different absorption pathways for iron in the intestine. Iron can be absorbed either as a free ion or heme-bound (most efficient absorption).
DMT1-(Divalent-Metal-Transporter-1) pathway : uptake of the ionic form Fe2+.
Important: this transporter is not selective and also takes up other ions such as zinc or copper. There is some competition for this transport!
HCP-1 (heme carrier protein-1) pathway: absorption of heme-bound iron.
Other mechanisms are currently being discussed, such as a transporter for ferritin, the storage form of iron in both plants and animals.
In addition, there is the possibility that trivalent iron can also be absorbed via cellular clefts or via chemical equilibria.
Iron transport in the blood: Iron is transported in the blood as transferrin and normally about 20-50% of transferrin is loaded with iron.
This is important ! This transferrin can be measured! You can also measure what percentage of the transferrin is loaded with iron. If there is less loading, one can assume too little iron !
Uptake into the target cells: When a cell needs iron, it expresses more transferrin receptors on its surface. Then transferrin binds to the transferrin receptor and the transferrin/ transferrin receptor complex fuses:
Iron enters the cell.
A lot of transferrin and low percent saturation is called iron deficiency.
Little transferrin and high saturation means iron excess.
And there are still many mechanisms that we do not even know yet!
Yes, it can be complicated!
Important!!! All of these processes can work differently for each of us genetically! Knowing this is very important. What works for one does not have to work for the other! All these mechanisms can work more or less well due to so-called genetic polymorphisms. One must know this!
Most of the iron (about 80%) enters the bone marrow and is directly incorporated into the heme! The stem cells are located in the bone marrow. New immune cells or blood cells are produced in the bone marrow!
More than 3 million new cells are produced per second !
The required iron comes to about 80% from the recycling of old, dead cells. This is the reason why only relatively little iron is needed with food. Because the body uses iron very sparingly and carefully ! Most of the iron circulates again and again. We lose iron only through blood, bile, stool and a little through the skin. But these are small amounts as long as we do not bleed chronically !
But how is the iron distributed in the body? Since free iron can be very toxic, it is almost exclusively present in protein-bound form. The most important iron proteins in humans are hemoglobin in blood (about 70%), myoglobin in muscle(about 10%), ferritin (about 15%), rest: enzymes, transferrin, cytochromes. But there is also neuroglobin in the brain!
So again:
Myoglobin (O2 binding and storage in muscle, also cardiac muscle! )
Hemoglobin (O2 transport by the red blood cells !)
Cytochromes of the respiratory chain (electron transport in the mitochondrion, ATP synthesis ! )
I will go into this in more detail in a new article, otherwise this would go beyond the scope here and also deviate too far from iron!
Why is this important to know ?
If you know where iron is distributed, you know where to look. And he also knows what happens in case of deficiency.
One measures hemoglobin in the blood. In case of iron deficiency, this value is too low.
Normal hemoglobin is 12 – 18 g/dl.
But !!! Measuring only one value is not enough. This is because the body is economizing.
Important systems continue to be supplied, although there is already a subclinical deficiency. The body prioritizes! Important !
Ferritin is a protein and is the iron store in animals and plants.
In the case of iron deficiency, the ferritin value in the blood is too low.
In the case of infections or tumors, the body tries to withhold iron from the cancer cells or pathogens. It tries to starve them out, so to speak. This causes the ferritin value to rise sharply.
Phytic acid in plants binds iron and excretes it.
Tumors depend on iron for growth.
A possible link between vegetarianism and cancer?
Ferritin is regulated by hepcidin. Hepcidin is a protein hormone and is produced in the liver. Hepcidin is the iron brake. Hepcidin means iron stop.
When there is too much iron, hepcidin is upregulated and the intestinal cells store iron in the form of ferritin, and excrete it through the stool! So hepcidin regulates iron absorption. And circulation. Availability.
The body urgently tries to avoid too much as well as too little iron!
Because it knows that it plays with fire !
So: the body iron homeostasis is carried out at the level of intestinal absorption.
where the peptide hormone hepcidin from the liver plays the key role. Hepcidin decreases iron absorption…….and inhibits iron transport. It also limits the loading of transferrin in plasma or the availability of iron to cells.
Hepcidin may be mutated!!! Each of us has a slightly different functioning hepcidin! In some, hepcidin is very defective!
Hepcidin is controlled by measuring oxygen in tissues through complex mechanisms. When there is a lack of oxygen in the tissues, hepcidin decreases!!!
The body is poor at distinguishing between iron deficiency and oxygen deficiency. Perhaps caused by clogged vessels, hepcidin decreases and thus iron uptake increases! And thus iron overload increases!
So poor blood flow or poor respiration is factually interpreted by the body as iron deficiency!!! It’s a survival strategy.
Short term survival, but long term damage?
Also, hepcidin synthesis is increased by IL-1 and IL-6. These are inflammatory messengers! Which leads to decreased intestinal iron uptake as well as iron release from ferritin.
Important: IL-1 and IL-6 are high in inflammation.
Meaning: this is essential in chronic inflammation. Liver disease also interferes with this.
Those who are sick have high hepcidin. Means: little iron is absorbed.
Important. One can have high hepcidin. And a lot of iron in ferritin. But in fact there is iron deficiency! Because all iron is stored. To starve the pathogen or tumor. There is a lot of iron stored, but it no longer circulates!
A vicious circle!!! Did you understand that?
Important: You have to take care of these chronic inflammations or liver diseases first, before you think of supplementing iron as a tablet!
These are all very complex mechanisms with many effects!
Who is chronically ill: cancer or is highly inflamed! This is where it gets complex! The body tries to hide iron to not further aggravate the disease!
Since there is no mechanism to regulate iron excretion, controlling absorption is the only target for regulating iron status in the body. The only loss occurs through stool and blood.
Iron is essential, but overload is toxic!
Important: You don’t have to understand all the mechanisms! But it is important to understand how finely regulated everything is !
As a laboratory value ferritin. Measuring iron in the blood does not make sense, because this value fluctuates very much.
Iron in is stored in the cells as ferritin, a part is released to the blood. This part is proportional to the ferritin in the cells. The ferritin in the blood thus represents an indicator of the organism’s iron reserves.
What does it mean?
Both too low and too high ferritin is bad.
Ideal ferritin values are between 70 – 120 ng/ml.
This value , ferritin , is measured in the blood.
Who has a ferritin value of over 150ng/ml does not need to supplement extra iron!
Who has a ferritin value above 300ng/ml could be sick !!!
What do you do if you have too little iron ?
Eat meat. Red meat or liver. If you cannot eat meat, you should first take tablets.
Important: Meat contains substances that are very important for a functioning iron metabolism ! Keyword: Copper , Vitamins
What do you do if you have too much iron ?
Eat less red meat. Live vegan. Or donate blood and bloodletting!
Iron is thought to be deposited in the pancreas and in the pituitary gland. Insulin is produced in the pancreas and testosterone is controlled in the pituitary gland.
How do we know how too much iron works and why it can be dangerous?
There is an iron storage disease called hemochromatosis. It is a disease in which the concentration of iron in the blood is increased.
In hemochromatosis, there is an increased absorption of iron by the small intestine. As a result, the concentration of iron in the whole body increases from about 2-6 grams to up to 80 grams.
This disease is associated with ferritin up to 1000ng/ml or even higher!
The cause is often a mutation in the HFE gene. HFE regulates iron metabolism.
If left untreated, the disease leads to irreversible organ damage due to deposition of iron over a long period of time. However, if diagnosed at an early stage, it can be treated.
And often with bloodletting!!!
What are the symptoms of these patients?
Diabetes mellitus, liver cirrhosis, diseases of the heart muscle, testosterone deficiency have been observed as long-term symptoms!
There are different forms of hemochromatosis, the most common is the one that is inherited. Treatment involves reducing the concentration of iron in the body. Various therapies are used for this purpose (bloodletting, medication, supportive dietary changes).
A genetic test can detect gene mutations responsible for the development of hereditary hemochromatosis.
But such a genetic test does not only have to be useful for sick people.
Because even as a normal person you can have unnoticed genetic mutations that affect the iron metabolism! Very few people know that!
For experts!!! The important mutations are often found in these genes:
Gene for the hereditary hemochromatosis protein HFE.
gene of hemojuvelin HJV
Gene of hepcidin HAMP
Gene of transferrin receptor
Gene of ferroportin SLC11A3
In 90% of hemochromatosis cases, one or more mutations occur in the HFE gene.
The HFE gene is frequently affected by mutations and can be traced back to about 4000 BC to a Celtic tribe.
Often, however, this mutation is not even noticed and affected people live with it without knowing it!
But now comes the important thing: You do not necessarily have to have these diseases!
You can also walk around as a healthy person with much too high amounts of iron without noticing it!
This is one of the reasons why vegetarian diets are often considered superior!
Diabetes mellitus, cirrhosis of the liver, diseases of the heart muscle, testosterone deficiency.
All things that can occur even as a normal person if you take too much iron ! About tablets or much meat!
Do you realize what this means? Instead of 5 grams 50 grams of iron in the body?
Do you know rusting? Iron that comes into contact with air and water! It rusts.
The same thing happens on a molecular level! And is part of the aging process!
And also many normal people can have way too much iron in them. While not 50 grams but maybe 15 grams ?
Iron is deposited in each of us. The older we get! I have called you ferritin. Ferritin can become the so-called hemosiderin. When there is an oversupply of iron, more and more ferritin is formed to bind the toxic iron. Ferritin is degraded and mutates to hemosiderin! Hemosiderin is an iron-containing protein complex that is counted among the storage iron. You can think of hemosiderin as a garbage dump! It’s junk that gets deposited! A mixture of iron, fats and proteins. Junkyard of the cell!
Hemosiderin is an insoluble complex and is pathological!
Iron from hemosiderin depots can be mobilized much worse than from ferritin.
Hello! There are cells, there this does not make anything ! Young, short-lived intestinal cells. If hemosiderin is deposited there, it does not matter, because they die after a few days anyway and are replaced. The same with skin cells. But brain. Heart. These are very long-lived cells. And that could also lead to Alzheimer’s disease. Brain diseases.
It is very complex.
So: Too much iron makes for poorer insulin action and diabetes!!! This is also known because of the iron storage disease hemochromatosis.
The more stored iron in the body the more insulin resistance !!!!
What does insulin resistance mean? High blood sugar, saccharified vessels and proteins. Accelerated aging! Broken vessels, heart attack. Insulin resistance is the way to metabolic chaos! Iron is a very important switch! Wake up !
The body cannot distinguish between iron deficiency and oxygen deficiency!
What consequences this has…..please think for yourself !
As I said everything is a balance between too much and too little !
Why low testosterone ? Testosterone increases iron absorption. So with too much iron, testosterone is reduced!
What can you do then?
You can donate blood, which also improves your insulin sensitivity.
But what does the iron deficiency do? What is with too little iron!
Tiredness, lack of concentration, weakness can be an indication of iron deficiency: little endurance, little strength. Depression.
Why? Iron availability regulates oxygen availability and thus regulates the oxygen binding capacity of the muscle. Brain. Kidneys……..
Important: Iron alone is not enough. Because iron must be processed. Must be bound via proteins. Proteins consist of amino acids. Among other things, heme is made from the amino acid glycine.
Globin also consists of amino acids. And the globin gene can also be mutated and lead to diseases. Example: α-thalassemia in the defect of α-globin. β-thalassemia when the β-globin is defective.
Those who have protein deficiency can also not use iron.
Unbound free iron has a toxic effect. Free radicals and rust.
The body is a symphony orchestra:
Iron is like a violin player, but needs other musicians to function.
A functioning iron metabolism may need:
Copper: cofactor of ferroxidases. Enzymes that keep iron in a certain oxidation state, ensuring that functional iron remains available and can circulate in the body.
Biotin, zinc, vitamin B6: important in heme synthesis.
And amino acids, because without protein, iron cannot be bound and is lying around freely toxic.
We know about 47 essential substances without which our body does not function. And then there are a number of almost essential substances.
Fatty acids, amino acids, minerals, vitamins. What is missing must be eaten or supplied via dietary supplements!
If one or more substances are missing, biochemical reactions can come to a standstill. It is like a traffic jam when driving a car! Nothing goes right anymore ! Everything takes longer…
We lose iron daily through exfoliated skin, fallen out hair and bowel movements.
What is the consequence of all the above?
Too little animal food lowers the ferritin values.
Those who eat a vegan diet will never be able to fill the iron stores.
The iron stores become depleted.
Without iron, much collapses:
1 Iron is a cofactor of an enzyme that produces a gas. We are talking about NO synthase: NO is a gas. Nitric Oxide.
This is important for the following:
Blood flow : eNOs in the blood vessel.
Memory : nNOs in neurons of the hippocampus
Immune system: iNOs in immune cells
2 Iron is cofactor of enzymes of hormone and neurotransmitter production in the brain:
Pleasure and drive: through tyrosine hydroxylase, dopamine is produced
Happiness and good sleep: tryptophan hydroxylase produces serotonin (happiness) and serotonin produces melatonin (sleep hormone) at night.
3 cytochrome enzymes contain iron:
Sex hormone synthesis. Cholesterol synthesis. Vitamin D synthesis.
Detoxification in the liver.
Antioxidants (peroxidase: detoxification of hydrogen peroxide, catalase: detoxification of hydrogen peroxide).
Energy metabolism in the cell and in the mitochondrion (the respiratory chain uses cytochromes to produce ATP).
Small digression: mitochondria are the power plants of our cells and produce energy in the form of ATP. The endosymbiont theory states that mitochondria used to be bacteria which were then taken up by the cells and now live in symbiosis with us. Mitochondria can multiply and are regulated by energy demand.
Iron serves there for the transport of electrons and as a cofactor of enzymes. The fact is: without iron, these mitochondria cannot function.
Important. As a summary:
Too little iron means fatigue, weakness, depression.
Too much iron means insulin resistance and diabetes, lack of testosterone, accelerated aging due to cellular rusting. With too much iron, the same thing happens to them as a piece of iron that sits in the rain for years: it rusts and breaks!
The body likes to have the middle. And can compensate a lot for a long time.
If they are vegetarian or vegan, or have heavy bleeding. Then more iron could help them.
If you eat a very meat-rich diet and have an undetected gene mutation that causes you to absorb and store a lot of iron, then iron reduction might make sense for you. And maybe even bloodletting.
Please forgive me for any mistakes in this text. If you find any mistakes, please point them out to me.
I will try to improve this article regularly and keep it up to date.
In conclusion:
Look for serum ferritin levels between 70 – 120 ng/ml.
Ferritin 30ng/ml would be too low. Ferritin 240ng/ml would be too high.
Also important is the hemoglobin value in the blood. 12- 18g/dl. However, this value remains constant for a long time!! although many other iron-dependent systems have been deficient for a long time!!!
Therefore, if you are interested, you can also measure:
Measurement of transferrin in the blood.
Saturation of the transferrin. Should be between 20 and 50%.
Who has too little iron eats red meat and liver. Or supplements with tablets.
Those who have too much iron live without meat and do bloodletting.
Otherwise, iron is deposited in the tissues and our whole body goes crazy.
And please remember: Do not blindly supplement iron when you are actually deficient in copper or deficient in vitamins or deficient in amino acids. Because then iron quickly becomes toxic. Often it is not iron deficiency, but actually copper deficiency.
I have shown you that iron must always be processed. Without copper, the ferrooxidases do not work. The enzymes that turn bivalent iron into trivalent iron and vice versa! Without amino acids iron can not be incorporated into hemoglobin or myoglobin, because that all consists of amino acids! Also do not forget vitamin B12 and folic acid. Otherwise the cell division does not function! But you know what ? All this is contained in meat. So amino acids, vitamins or copper. You just have to be more careful with the tablet.
And do not forget that in each of us there are small genetic variations that affect all enzymes, transporters, channels and structures.
What is your experience with iron? How are your iron levels?
Do you eat a vegetarian or meat-heavy diet?
Sources:
Rassow et al.: Duale Reihe Biochemie. 2. Auflage Thieme 2008, ISBN: 978-3-131-25352-1.
Heinrich et al. (Hrsg.): Löffler/Petrides: Biochemie und Pathobiochemie. 9. Auflage Springer 2014, ISBN: 978-3-642-17971-6.
E.D. Weinberg Ph.D.Exposing the Hidden Dangers of Iron: What Every Medical Professional Should Know about the Impact of Iron on the Disease Process, 1. Juli 2004
Dr. sc.med. Bodo Kuklinski. Mitochondrien, 1. Auflage 2015
Thomas Karow, Pharmakologie und Toxikologie, 26. Auflage 2017