Ferritin and Iron
What is Ferritin?
Ferritin is an intracellular (inside the cell) protein, in the shape of a hollow sphere. Ferritin stores iron by allowing entry of iron as ferric hydroxide phosphate complexes, and when the body needs iron, releases it as required.
Ferritin is produced by almost every living organism, from bacteria to plants, animals and humans.
In humans, ferritin is a buffer against iron deficiency and iron overload, and is found in most tissues as a cytosolic protein, which means it is inside the cytoplasm, the fluid inside each cell between the outer shell wall and the nucleus (The nucleus contains our DNA).
However, small amounts of ferritin are secreted into the serum (blood) where it works as a carrier of iron.
Plasma ferritin (in the blood) is also an indirect marker of the total amount of iron stored in the body. Serum ferritin levels are used to determine iron deficiency (anaemia) or iron overload.
Ferritin keeps iron in a soluble, non-toxic form. Free ferritin (not combined with iron) is called apoferritin.
Iron is the central atom of haemoglobin, which gives blood it’s red colour. 75% of the body’s iron is stored in haemoglobin, 10 to 20% in the protein ferritin, and the rest in the protein transferrin (the iron transport protein). Small amounts are found in myoglobin, cytochromes, as unbound serum iron and in body tissues.
Excess iron is usually stored in the Liver, Spleen and Bone Marrow, but also in the Pancreas, Joints, Skin, Pituitary, Adrenals, Thyroid, Heart and other organs.
The haemoglobin molecule is a very large molecule, almost identical to the Chlorophyll molecule in plants. Chlorophyll has a central atom of Magnesium, giving grass the green colour. Haemoglobin has Iron as the central atom, giving blood the red colour.
Chlorophyll is commonly best known for “cleansing of the blood”. Best sources are green leafy vegetables and wheatgrass.
Why do we need Iron?
If we have too little iron, we cannot make enough red blood cells, reducing our ability to carry oxygen to all parts of the body.
If we have too much iron, it can damage organs and contribute to cancer, heart disease, the entire cardiovascular system, especially the endothelial cells (the inside lining of all blood vessels), the kidneys and the liver.
Red blood cells are made in the bone marrow, and have a lifespan of around 4 months, when they die (the process called Necrosis).
The body makes around 200 billion new red blood cells every day, along with around 10 billion white cells and about 400 billion platelets every day, and around the same amount die every day.
Dead red blood cells are then broken down by Macrophages (special white blood cells) in the spleen. Some are disposed of in the digestive tract (which makes our poo brown) and parts of other cells are re-used. Haemoglobin is further broken down to salvage the iron, and excess iron is then stored in the liver.
Too much iron in the liver can cause Cirrhosis (Scar tissue replacing healthy cells).
We can have too much iron in some cases because the body does not know how to get rid of excess iron, it only knows how absorb it and to store it (using the transferrin protein).
Healthy red blood cells.
As red blood cells approach death, or are infected with a parasite or bacteria, or have a genetic defect, or are cancerous, the shape, size, smoothness and colour may be different.
How is Iron absorbed?
Iron in food is processed in the high-acid stomach, where it is changed into a form that allows it to be absorbed.
Absorption takes place mainly in the duodenum (part of the small intestine) and also to a lesser extent near the end of the small intestinal tract.
After absorption, iron is transported by the transferrin protein. A healthy body has the ability to absorb more iron when it is required, and absorb less when it is not required.
Haemoglobin, Hemoglobin or Hbg
Haemoglobin is a protein contained in red blood cells.
The job of haemoglobin is to carry oxygen from the lungs to all of the tissue in the body, then return carbon dioxide back to the lungs.
Haemoglobin is composed of four globulin chains (protein molecules) which are connected together, and in adults, haemoglobin contains two alpha-globulin chains and two beta-globulin chains.
In foetuses and infants, haemoglobin contains two alpha chains and two gamma chains, and during growth to an adult, gamma chains are slowly removed, replaced by beta chains to form adult haemoglobin.
Every globulin chain contains the heme molecule as the central structure, and iron is embedded in the heme molecule, essential for the transport of oxygen and carbon dioxide.
Haemoglobin is also essential to help maintain the shape of every red blood cells, which resemble a donut with a dished centre rather than a hole. Any abnormal shape can cause poor flow through blood vessels.
Anaemia is a condition where we do not have enough haemoglobin, which is usually, but not always, related to iron deficiency. It can be related to blood loss, from donating blood, from heavy menstrual bleeding, internal bleeding, blood loss from an injury, or insufficient iron in the diet (such as vegans or vegetarians).
IDA (Iron Deficiency Anaemia)
In most cases of anaemia, a blood test will reveal low haemoglobin and low ferritin, a result of iron deficiency, and the doctor will normally recommend iron supplementation or dietary changes or both.
ACD (Anaemia of Chronic Disease)
The body has a safety mechanism against harmful invaders such as cancer or bacteria. When sensing an invader, the body will move all iron it can from red blood cells back to ferritin, because all invaders need iron to thrive, and so does cancer. The body will leave just enough iron in haemoglobin for the cells to survive, but not enough to feed the invader.
We must NEVER take extra iron in cases of Chronic Disease, as we are only feeding the invader and doing more harm to our body.
ACD can be diagnosed by blood tests where we have low haemoglobin, but high ferritin. A C-Reactive Protein test (indicator of inflammation) is advised as well as ferritin if ACD is suspected.
When the disease clears up, the body will automatically return iron levels to normal.
Many doctors do not order ferritin tests when iron is low, resulting in the patient taking iron supplements which can cause damage or even death, so an accurate diagnosis of IDA or ACD is essential.
In some cases, IDA and ACD can occur at the same time, making diagnosis more difficult. One traditional test is Bone Marrow Aspiration with Iron Staining, but the Serum Transferrin Receptor test can help differentiate between IDA and ACD.
The Serum Transferrin Receptor test is significantly less affected by inflammation than the Serum Ferritin test. Results can be high in IDA and usually low in ACD, and the ratio of Serum Transferrin Receptor to the logarithim of Serum Ferritin Concentration is more helpful to distinguish ACD from IDA than is either individual test.
If the patient has any kidney damage (sometimes as a result of high iron) then it is possible to have high iron in the body tissues, while regular iron and ferritin tests results are normal or even low. In these cases, a specialist should supervise all testing.
Normally, the doctor will organise a “Ferritin Study”.
This includes the following tests:
- Serum Iron – how much iron is circulating in the blood, but this varies considerably and does not always mean a lot without also looking at the TIBC test below.
- Serum Transferrin – or TIBC (Total Iron Binding Capacity) or Transferrin Saturation. Iron is bound to transferrin (which is produced by the liver), and TIBC is a direct measure of transferrin. Iron overload is indicated with levels over 55% for males and 50% for females. Fasting is preferred for accuracy. Note that inflammation causes reduced transferrin levels
- Serum Ferritin – Indicates body iron stores. Typical lab results: Normal range 15 to 350 ug/L for men (some labs say up to 500ug/L), 15 – 300 ug/L for women, and varies depending on the lab and the method used, however LeanMachine says that these upper limits are way too high, and that anything over 80 ug/L indicates a possible iron overload condition, and anything below 20 ug/L indicates a possible iron deficiency. A healthy range is 20 to 80 ug/L, and the desirable range is 40 to 60 ug/L, but note that levels over 80 ug/L may be also be caused by liver disease, inflammation or cancer
- Soluble Transferrin Receptors – Transferrin receptors present on cell surfaces are responsible for internalization of transferrin resulting in intracellular release or iron. With low iron stores, expression of transferrin receptors increases, so the level of soluble transferrin receptors inversely reflects iron stores, and is unaffected by any inflammation, however high soluble transferrin receptors may also mean haemolysis (premature red cell death)
- A complete blood examination is also required to check Haemoglobin and other factors related to red blood cells, also liver and kidney function. Typical haemoglobin blood results 130g/L to 170g/L for adult males, 120g/L to 150g/L for adult females. For more info on these tests, see my article Blood Tests – How to read the results
- Further tests may include a Liver Biopsy, SQUID (Superconducting Quantum Interference Device), or MRI (Magnetic Resonance Imaging), but these are generally not required except for extreme cases
Note that these are Australian tests. In the USA, the results are in ng/ml (nanograms per millilitre), which is exactly the same as ug/L (micrograms per litre), with upper and lower numbers both divided by 1000, giving the same numerical result.
Types of dietary Iron
There are two main types of dietary iron, heme iron found in meat and other animal products, and non-heme iron found in plant products.
Generally, heme iron is better absorbed than non-heme iron, leaving vegans more at risk for iron insufficiency, however heme iron is also more dangerous for the body in high levels.
A healthy body self-regulates iron levels, by absorbing more iron when we need it, and absorbing less iron when we do not need it, but sometimes this regulation is upset or overloaded.
Factors affecting ferritin/iron levels
Menopausal women often (but not always) have low iron, especially if periods are heavy, while post-menopausal women usually have normal iron.
Pregnancy increases iron requirements, as the body needs to make around 30% more blood to support the developing foetus, requiring 30% more iron. The body will use the body’s stored iron, but if stored iron is insufficient, anaemia will occur. All pregnant women should get their iron and haemoglobin tests done at each trimester, especially if diet or other factors place them at risk.
Blood donors will often have low iron. Red Cross blood donation centres always test haemoglobin levels, and if too low (or even too high), that person cannot donate blood.
For an adult male, the normal range is 125g/L to 185g/L
For an adult woman, the normal range is 115g/L to 165g/L.
For donations of whole blood for males, the acceptable range is 120 to 165g/L for women, and 130 to 185g/L for men.
For donations of plasma and platelets, the acceptable range is 115 to 165g/L for women, and 125 to 185g/L for men.
If below 130 (male) or 120 (female), that person should build up their iron reserves and seek medical advice.
Bleeding in the GI (Gastro-Intestinal) tract can cause low iron, as in any other form of blood loss.
Bleeding because of haemorrhoids or anal fissures, or bleeding from cancer or inflammation in the small intestine, colon or stomach will cause low iron. If stools are dark, or blood in urine, or any unexplained abdomen pain, see your doctor.
Various foods and vitamins can increase or decrease iron absorption – see below.
Foods high in iron are also generally high in Vitamin B12, and both are required for correct ferritin/iron metabolism and healthy Red Blood Cells.
Vegetarians and vegans in particular are susceptible to low iron and B12, as both come mainly from animal products.
As we age, we tend to have reduced stomach acid, resulting in less B12 absorption, and to a lesser extent, reduced absorption of all other minerals, vitamins and other nutrients.
If we take supplemental iron, the body will absorb less iron from the diet.
If we have a low-iron diet, the body responds by absorbing more iron from anything available in food.
Sickle cell disease, thalassemia and haemochromatosis can all be inherited, and genetic testing for these and other genes affecting ferritin/iron is available.
Sickle Cell Anaemia
An inherited condition, mainly descendants of African people. A problem with the haemoglobin beta gene causes some red blood cells to become sickle-shaped, especially in hot, dry and intense exercise conditions.
25% of the population in West Africa have the sicklemia trait, also high in South and Central Americans, especially in Panama. Sometimes appears in Mediterranean countries like Italy, Greece, and Spain. Malaria may be a factor, as Indians, Middle Easterners (e.g. Arabs and Iranians), Native Americans, North Africans, and Turks have small but significant cases.
People with Sickle Cell Anemia actually have an advantage in some countries, as they are able to survive better if infected with Malaria. The “sickleing” of the red blood cells is promoted when the Malaria parasite enters, and the body’s own immune system is then able to identify and destroy the cell, along with the malaria parasite.
An inherited condition, originating in Mediterranean countries, causing weakening and destruction of red blood cells by mutant genes, affecting haemoglobin production. Similar to Sickle-Cell Anaemia.
Haemochromatosis (inherited iron overload disorder)
There is a genetic test for Haemochromatosis.
The test gives results for mutations C282Y and/or H63D of the HFE gene:
- Mutation not found (No Haemochromatosis)
- Heterozygous (which means one faulty gene) – Generally no or mild symptoms, bu bay be a “carrier” for children
- Homozygous (which means two faulty genes)
Children of a Mother and Father who are both carriers of one faulty gene have:
- 50% risk of inheriting one mutated HFE gene (and becoming a carrier)
- 25% risk of inheriting both mutated HFE genes (and at risk of excess iron absorption and symptoms of haemochromatosis)
- 25% risk of inheriting two normal genes, and will not be a carrier
Around 1 in 188 Australians have the HFE genotype C282Y mutation, the most dangerous kind, although 1 in 8 people are carriers for this gene. There are many primary (inherited) types, including:
- Type 1 – Classical haemochromatosis – Gene Mutation – HFE Genes C282Y and H63D, often with variations. C282Y is more serious.
- Type 2A – Juvenile haemochromatosis – HJV (Haemojuvelin), also known as RGMc and HFE2 Genes
- Type 2B – Hepcidin antimicrobial peptide (HAMP) or HFE2B Gene
- Type 3 – Gene Mutation – Transferrin receptor-2 (TFR2 or HFE3 Genes)
- Type 4 – African Iron Overload – Ferroportin (SLC11A3/SLC40A1 Genes)
- Neonatal haemochromatosis – unknown cause
- Acaeruloplasminaemia (very rare) – Caeruloplasmin
- Congenital atransferrinaemia (very rare) – Transferrin
- GRACILE syndrome (very rare) – BCS1L Gene
Also secondary types, which are not inherited, but acquired, especially if the patient has received many repeated blood transfusions.
- Severe chronic haemolysis – either intravascular haemolysis or ineffective erythropoiesis (haemolysis within the bone marrow)
- Excess iron from the diet
- Excess iron from supplements. Any supplements must be kept away from children. This is a common cause of childhood poisoning
Conditions may involve mutant genes inherited from both parents, so patients may have widely differing symptoms.
1 in 700 people with haemochromatosis have no mutation in the HFE gene. This is called Non-HFE haemochromatosis, due to mutations in other genes.
Symptoms of Low Ferritin/Iron
- Brittle Nails and/or spoon-shaped fingernails
- Intolerance to Cold
- Craving or Eating Non-Foods – dirt, hair, coins, etc (Pica)
- Irritibility, Loss of Concentration, Dizziness
- Pale appearance, especially membranes – inside of mouth and eyelids
- Increased infections
- RLS (Restless Leg Syndrome)
- Shortness of Breath
- Loss of Appetite
- Mouth Ulcers
- Dry Mouth and/or Sore Tongue
- Tachycardia (faster than normal heartbeat
- Arrhythmia (irregular heart beat)
- Loss of Consciousness (Syncope)
- Enlarged spleen
- Vitamin B12 deficiency
- Vitamin D3 deficiency
Symptoms – High Ferritin/Iron
- Chronic fatigue, tiredness, weakness
- Low levels of L-Glutathione
- Low levels of antioxidants
- Joint pain or aches
- Abdominal pain
- Diabetes mellitus (Type 2)
- Arrhythmia (irregular heart beat)
- Congestive heart failure
- Heart attack
- Changes in skin colour to bronze, ashen-grey or green
- Period is irregular or stops (women)
- Low Libido
- Hair loss
- Enlarged liver or spleen
- Impotence (men)
- Mood swings
- Low adrenal function
- Neurodegenerative disease
- High blood glucose
- High liver enzymes – ALT, AST, GGT
- High serum iron and serum ferritin
- Higher risk of cancer
- Weight Loss
How Much Iron do we Need?
Depends on who we are.
For post-menopausal women and healthy men, 8mg daily.
For menopausal women or blood donors, 18mg daily to replace iron in lost blood.
For pregnant women, 27mg daily for rapid growth and development.
Many breakfast cereals give all of menopausal women’s iron requirement, two-thirds the amount required for pregnancy, but double the amount for men and post-menopausal women, not counting intake from other meals.
Typically, there is a total of 3 to 4 grams of iron in the body. A normal diet should give most people enough iron, but vgans and vegetarians and blood donors will oten be lacking. People consuming large quantities of meat, especially liver meats, can reach iron overload withour knowing.
To INCREASE Ferritin/Iron
- Some breakfast cereals are fortified with extra iron
- Red meat – beef, lamb, kangaroo and organ meats, especially liver are rich in iron
- Low alcohol consumption (one drink daily with food) is fine, but overdoing it will cause liver damage
- Vitamin C (orange juice, fruit, supplements) will increase absorption of iron from food, up to 6 times greater absorption
- Avoid donating blood too often, or not at all if haemoglobin is less than 130 (men) or 120 (women)
- Build testosterone, by diet and exercise and/or supplementation to help build new red blood cells
- If vitamin B-12 and/or Folate is low, supplement or change diet
This is a dangerous condition, and if iron overload is suspected, a ferritin study is required. See above under “Blood Tests”.
To DECREASE Ferritin/Iron
Blood donation (therapeutic venesection) is usually the best method, and helps save lives of others.
If ineligible for Red Cross donations, private organisations can do this. Usually a ferritin reading of several hundred can be brought down to the normal range after half a dozen or so blood donations.
The only down side is that donations must be spread out over many months to allow the body to build new blood.
Next best option is using IP6 (Inositol Hexaphosphate) which can chelate excess iron from the body.
IP6 can help when the body cannot excrete excess ferritin/iron on it’s own, which can often happen. The body has limited capacity to remove iron, as it tries to always recycle iron.
Also the best alternative when blood donation is impossible, impracticable or ruled out for religious reasons.
IP6 has the added benefit of improving immunity.
More serious cases of iron overload can be treated with:
Deferoxamine (Desferal®) – administered via a needle from a pump attached to the body for 8 to 10 hours a day.
Deferasirox (Exjade®) – a tablet dissolved in a glass of water or juice, taken once a day.
Both methods can have undesirable side-effects, including hearing and vision loss, nausea, diarrhea, rash, kidney or liver injury, so LeanMachine recommends first using blood donation, IP6 and diet measures first.
- Donate Blood at the Red Cross. Reduces old blood recycling, leading to reduced iron stores which are used up in making new blood. May take several sessions over several months
- Take IP6 (Inositol Hexaphosphate)
- Eat cabbage every day (cooked, not raw). No scientific studies have been carried out with cabbage, but plenty of anecdotal evidence suggest it works, possibly by filling up on cabbage, the patient may not feel like red meat…
- Avoid red meat, and especially liver and other organ meats
- Drink green tea, black tea, oolong tea or coffee, and/or take a Green Tea Extract. The tannins in tea reduce iron absorption
- Take Vitamin E, Vitamin B-6, Curcumin
- Avoid taking too much Vitamin C, as this can increase iron absorption
- Do not cook in iron pots or pans, even if you have low iron, as metallic iron is bad for the body, regardless of the Ferritin status
- Avoid alcohol, especially wine with steak
- Never take iron supplements. If you take a multivitamin, or a “women’s health” or “men’s health” supplement, ensure it has no iron
- Never drink well water or bore water unless it has been tested free from iron (and other harmful metals)
- Take Astaxanthin – an extremely powerful antioxidant, 550 times better than Vitamin E. Will not chelate iron, but will help repair the damage
The Low-Iron Diet
Green Tea, black tea, oolong tea and coffee all contain tannins which inhibit iron absorption, so drinking these with a meal can help lower ferritin and iron levels.
Drinking milk with a meal also helps reduce iron absorption because of the calcium in milk that competes with iron for absorption.
Eat an egg every day, as eggs contain a compound that impairs absorption of iron. Avoid red meats, chicken and fish are better choices, much lower in iron than red meat. Better still, go vegetarian or vegan.
Calcium supplements can reduce iron absorption, but can also cause increased plaque in arteries, especially the Calcium Carbonate (ground limestone) used in cheap supplements, so should be avoided.
Breakfast cereals with whole grains contain some iron, but many are fortified with extra iron and should be avoided. Try an apple for breakfast instead and help keep the doctor away.
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Open2Study, Australia – Food, Nutrition and Your Health
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Johns Hopkins Bloomberg School of Public Health, USA – Health Issues for Aging Populations
Johns Hopkins Bloomberg School of Public Health, USA – International Nutrition
Johns Hopkins Bloomberg School of Public Health, USA – Methods in Biostatistics I
Johns Hopkins Bloomberg School of Public Health, USA – Methods in Biostatistics II
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Technical Learning College, USA – Western Herbology, Identification, Formulas
Bath University, England – Inside Cancer
WebMD Education – The Link Between Stroke and Atrial Fibrillation
WebMD Education – High Potassium: Causes and Reasons to Treat
Leiden University Medical Center, Netherlands – Anatomy of the Abdomen and Pelvis
MIT (Massachusetts Institute of Technology) – A Clinical Approach to the Human Brain
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Updated 13th January 2020, Copyright © 1999-2020 Brenton Wight and BJ & HJ Wight trading as Lean Machine abn 55293601285