Hemochromatosis and Autoimmune Conditions


The Living Force
FOTCM Member

What is hemochromatosis?

Hemochromatosis occurs when the body absorbs too much iron from foods (and other sources such as vitamins containing iron). This disease causes extra iron to gradually build up in the body's tissues and organs, a term called iron overload. If this iron buildup is untreated, it can, over many years, damage the body's organs.

What are the causes?

Although hemochromatosis can have other causes, in the United States the disease is usually caused by a genetic disorder. A person who inherits the defective gene from both parents may develop hemochromatosis. The genetic defect of hemochromatosis is present at birth, but symptoms rarely appear before adulthood. Because one inherits genes from his or her parents, this type of the disease is also called hereditary hemochromatosis.

What are the symptoms?

Early indications of hemochromatosis include the following symptoms:

* Fatigue (feeling very tired)
* Weakness
* Weight loss
* Abdominal pain
* Joint pain

Because these symptoms also occur with other diseases, hemochromatosis can be difficult to diagnose in its early stages.

How is it detected?

The iron overload associated with hemochromatosis can be detected through two blood tests. The tests measure how much iron is in the body. You can have these tests done in your doctor's office.

If hemochromatosis is detected early, treatment can slow its progress and prevent serious problems. However, if the disease is not detected and treated early, it can cause more serious problems. These problems include arthritis, heart problems, and liver problems (such as cirrhosis and liver cancer).

What is the treatment?

Treatment consists of periodically taking blood from the arm, much like giving blood. The treatment is safe and effective. Patients can expect a normal life span if they start treatment before organ damage has begun.

Signs and Symptoms

Hemochromatosis can have a variety of symptoms and symptoms may be different for men and women. Hemochromatosis can be hard to identify because early symptoms are similar to those of many other common diseases.

Although most people reach middle-age before they have symptoms of hemochromatosis, some people may have symptoms at a younger age. The symptoms depend on which organs are being affected by the iron buildup.

Early Symptoms of Hemochromatosis

Early indications of hemochromatosis are often like those of other diseases and include the following symptoms:

* Fatigue (feeling very tired)
* Weakness
* Weight loss
* Abdominal pain
* Joint pain

As iron builds up in the body organs, hemochromatosis may also produce the following symptoms:

* Loss of menstrual periods or early menopause
* Loss of sex drive (libido) or impotence
* Loss of body hair
* Shortness of breath

Although not a physical symptom, another possible indication of hemochromatosis is having an elevated liver enzyme test.

Advanced Symptoms of Hemochromatosis

As the disease progresses, hemochromatosis may cause the following more serious problems:

* Arthritis
* Liver problems, such as cirrhosis (or scarring of the liver) and liver cancer
* High blood sugar and diabetes
* Abdominal pain that does not go away
* Severe fatigue (feeling extremely tired and having a lack of energy)
* Heart problems (such as a heart beat that is not regular)
* Heart failure (such as the heart not pumping blood as well as it did previously)
* Gray-colored or bronze-colored skin

Key Point

Early symptoms of hemochromatosis, such as feeling very tired, pain in the joints, weakness, weight loss, and abdominal pain, are like the symptoms of other diseases, but may indicate the presence of iron buildup and hemochromatosis. Elevated liver enzyme tests may also indicate the presence of iron buildup and hemochromatosis.

Causes and Risk Factors

In the United States, the most common form of hemochromatosis in adults is called hereditary hemochromatosis or classic hemochromatosis. This form of the disease is caused by a defect in the genes that control how iron is absorbed by the body.


The amount of iron the human body absorbs is controlled by many genes. Genes can sometimes change (or mutate) in ways that keep them from working properly.

Hereditary hemochromatosis can occur when a person inherits two mutated copies of a gene called the HFE gene - one from each parent. Men and women have the same chance of inheriting two copies of this gene.

Not everyone who is born with two copies of the mutated HFE gene develops the disease. Scientists do not know what percentage of people who have two copies of the mutated HFE gene develop the disease. Some studies have shown that as few as 1 in 100 people will develop symptoms. Other studies have shown that as many as 50 in 100 people may develop symptoms. A person with only one copy of the mutated HFE gene is usually healthy and is said to be a "carrier" of the genetic condition. Although a carrier usually does not have hemochromatosis, if both a mother and father are carriers, a child may inherit two copies of the mutated gene, one from each parent.

Risk Factors

People who inherit the HFE gene mutation from both parents are at the greatest risk for developing hemochromatosis. Although both men and women can inherit the gene defect, men are more likely to be diagnosed with the effects of hemochromatosis than women. Other factors that increase risk are listed in the following table.

Ethnic background

White people of northern European descent (for example, families from England, Ireland, Scotland, Denmark, France, and Scandinavia) have a higher chance of having the HFE gene mutation.

Family history

People with a close relative (grandparent, mother, father, sibling, niece, nephew) who has hemochromatosis have a higher chance of having the HFE gene mutation.

Factors That May Affect Iron Buildup

For people at risk of developing hemochromatosis, the speed at which iron builds up and the severity of the symptoms vary from person to person. Many people do not have any early symptoms. Symptoms tend to occur in men between the ages of 30 and 50 and in women over age 50. The following factors may affect the buildup of iron in the body and may speed up or slow down the development of hemochromatosis.

Use of dietary supplements

Taking iron supplements or multivitamins with iron can speed up the rate at which iron builds up in the body. Persons with hemochromatosis should not take pills containing iron. Eating foods that contain iron is fine.

Taking vitamin C supplements may cause the body to absorb more iron. Persons with hemochromatosis should not take pills with more than 500 milligrams of vitamin C per day. Eating foods that contain vitamin C is fine.

Blood loss

Losing iron by giving blood and losing iron through menstruation and unrecognized bleeding may slow the start of hemochromatosis. Therefore, men at risk for hemochromatosis usually develop the disease and its symptoms at a younger age than women who are at risk.

Key Point

People with the HFE gene mutation may absorb extra iron from their diet each day. Over many years, this extra iron may cause a buildup of iron in the body that can lead to disease. Persons with hemochromatosis should not take pills containing iron.

Detection and Diagnosis

Most regular medical check-ups do not include tests to measure the amount of iron in the body. For that reason, hemochromatosis is often not identified in people who have the disease.

If you think you have symptoms like those of hemochromatosis, (fatigue, weakness, abdominal pain and/or joint pain), or if you have a close relative who has hemochromatosis, you should ask your health care provider to check the amount of iron in your blood.

Early detection of iron buildup is important because prompt diagnosis and treatment of hemochromatosis can help prevent the more serious problems caused by the disease.

To see if you might be at risk for hemochromatosis, a doctor will take a complete medical history and give you a physical examination. Having information about your family's health history is also helpful.

To check the amount of iron in your body, a doctor can use two simple blood tests: Transferrin saturation (TS) test, Serum ferritin (SF) test.

If these tests show that you have too much iron in your body, you will need to start phlebotomy (pronounced "fle-bot-o-me") treatment.

Transferrin Saturation (TS) Test

You should not eat after midnight on the night before your blood is drawn for the transferrin saturation (TS) test.

If, on an empty stomach, your TS value is greater than 45%, you should have a serum ferritin test done.

Note that taking any of the following supplements or pills in the day prior to your blood draw can make TS values higher than normal: Multivitamins with iron, Multivitamins or pills with vitamin C, Medicinal iron.

If you take any of these supplements or pills, you should not use them for 24 hours before blood is drawn for the TS test.

Serum Ferritin (SF) Test

For information about interpreting the serum ferritin (SF) test, see the following table.

For women

If you have not been through menopause, an SF greater more than 200 ng/mL (nanograms per milliliter) means there is too much iron in your body. If you have been through menopause, an SF value greater than 300 ng/mL means there is too much iron in your body.

For men

An SF value greater than 300 ng/mL means there is too much iron in your body.

These blood tests, a thorough medical history, and a physical examination may also help rule out other conditions that could be causing the symptoms.

Key Point

If you think you have symptoms like those of hemochromatosis or if you have a close blood relative who has hemochromatosis, you should ask your health care provider to check the amount of iron in your blood.

Treatment and Self-Care

Hemochromatosis can be treated simply and successfully. The treatment, called phlebotomy (pronounced "fle-bot-o-me"), removes blood to lower the amount of iron in the body. The treatment is similar to giving blood and is the best way to treat the disease.

If phlebotomy treatment is started before too much iron has built up in the body, it can stop many of the serious problems of hemochromatosis.

* If you have no organ damage and get proper care, you can expect to live a normal life.
* If you already have organ damage, treatment can stop additional damage, but it cannot reverse damage that has already started.
* Even if you have developed serious problems, treatment can lessen many symptoms and improve your quality of life.

Important things to know about phlebotomy treatment for hemochromatosis:

* Drink plenty of water, milk, or fruit juices both before and after the treatment.
* Avoid vigorous physical activity for 24 hours after your phlebotomy treatment.
* Be sure to keep your phlebotomy appointments as directed by your doctor.

Treatment Process

The phlebotomy treatment consists of two phases: an "iron reduction" phase and the long-term maintenance phase.

Iron Reduction Phase

In the iron reduction phase, a health care professional removes about one pint of whole blood, usually once or twice a week.

This phase usually lasts until all of the extra iron stored in your body has been removed. It can take three months to one year, but the time varies from person to person. Age, gender, the cause of the iron overload, and severity of symptoms all affect how long this phase takes. During this phase, your doctor checks your hemoglobin and serum ferritin levels.

Long-term Maintenance Phase

Once the extra iron has been taken out, your doctor will set up a long-term maintenance program to make sure you keep a normal amount of iron in your body.

How often a person needs phlebotomy during this phase varies based on the severity of the symptoms. During this phase, your doctor continues to check your hemoglobin and your serum ferritin levels.


Hemoglobin is a protein that is a found in red blood cells; about 75% of the body's iron is bound to hemoglobin which is involved in oxygen transport from the lungs to the rest of the body.

Regular phlebotomy treatment keeps the amount of iron in your body at a normal level. A normal amount of iron is between 25 and 50 ng/mL (nanograms per milliliter).

* Men usually need to have 3 to 4 pints of blood taken out each year (about once every 3 months) to maintain this level.
* Women may need to have 1 to 2 pints of blood taken out each year (about once every 6 months) to maintain this level.
* Some people, especially older people, may not need to have any more treatments, but they should still have their serum ferritin level checked at least once a year.

If you have hemochromatosis, you should have your serum ferritin level checked at least once a year. Doing so can help keep your iron level within the normal range and avoid the serious problems caused by too much iron.

Donating Blood

Many patients and their doctors ask if it is safe for people with hemochromatosis to give blood. The U.S. Food and Drug Administration (FDA) has stated that blood from hemochromatosis patients can be used for people needing blood if the facility where the blood is donated meets the following rules:

1. The blood collection center cannot charge a fee for collecting the blood.

2. The blood center must apply to the FDA to be exempt from the existing rules.

Key Point

Most people with hemochromatosis should be checked at least once a year to be sure that their iron level is within the normal range. If the iron level is too high, phlebotomy treatments are needed to keep extra iron from building up in the body.

Self-Care Tips

There is much you can do to make sure your life is as normal and healthy as possible.

Check-ups: Have the amount of iron in your blood checked regularly.

Phlebotomy: Make sure to get phlebotomies when you need them.

Iron pills: Don't take iron pills, supplements, or multivitamin supplements that have iron in them. Eating foods that contain iron is fine.

Vitamin C: Vitamin C increases the amount of iron your body absorbs. Avoid taking pills with more than 500 mg of vitamin C per day. Eating foods with vitamin C (such as oranges) is fine.

Food: Don't eat raw fish or raw shellfish. Cooking destroys germs harmful to people with hemochromatosis. People with hemochromatosis are at greater risk for bacteremia, a bacterial infection of the blood stream.

Alcohol: If you choose to drink alcohol, drink very little. Women should have no more than one drink a day. Men should have no more than two drinks a day. However, if you have liver damage, do not drink any alcohol.

Exercise: You can exercise as much as you want. The CDC and the American College of Sports Medicine offers the following physical activity recommendations:

Adults should engage in moderate-intensity physical activities (indicated by some increase in breathing or heart rate) for at least 30 minutes on most preferably all days of the week.

Key Point

Phlebotomy is the best treatment for hemochromatosis. Hemochromatosis cannot be treated by changing your diet alone.

Information for Relatives

If you find out that you have hemochromatosis, encourage your immediate family members (grandparents, parents, brothers, sisters, and adult children older than 25) to be tested for the amount of iron in their blood.

If you have hemochromatosis, your brother or sister has a 1 in 4 chance (25%) of having two HFE gene mutations.
If you have hemochromatosis, your children have about a 1 in 20 chance (5%) of having two HFE gene mutations.
It is important to remember that not all people with two HFE gene mutations will develop hemochromatosis.

In persons with a family history of hemochromatosis, genetic testing can determine who in the family does not have the HFE gene mutation. However, measuring the amount of iron in the blood is more helpful than genetic testing for detecting iron buildup and hemochromatosis.

Key Point

Measuring the amount of iron in the body with a simple blood test is more helpful than genetic testing for detecting iron buildup and hemochromatosis.
A year went by, the KD came along, and naturally she went on that. At first, things went well, but then, bizarrely, everything positive started to reverse and a whole host of symptoms came to the fore.

Indeed. And there might be a clue here:

Celiac disease is linked to a very rare genetic disease of iron overload, called hemochromatosis. (Symptoms include chronic fatigue and abdominal pain, among others.) People with celiac disease who also have hemochromatosis may not know it because the malabsorption of celiac protects them from accumulating too much iron—until they go gluten free. As they change their diet, their intestines heal and their iron levels can rise dangerously. Serum ferritin is the best test to screen for iron overload.

And about the same is said here: http://www.livestrong.com/article/550942-gluten-intolerance-skin-hives-hemochromatosis/

If the what the above quote says is true, then no wonder she started developing all those symptoms after we went gluten free! On the other hand, it might be a blessing, since it can also mean that her gut is much healed, which can help enormously once she starts doing the bleeding regularly.

This makes me think that it is very likely that some of the symptoms reported by members of the forum when they started cutting off gluten might also be the related, indeed.

I'm too tired to keep digging right now, but hopefully some of you will find more info on this, and studies. I've also read that there are several skin conditions associated with hemochromatosis, including psoriasis, and possibly hydradenitis suppurativa. So, it might be worht exploring some more, and donating blood in the meantime.

What Is Hemochromatosis?

Hemochromatosis (HE-mo-kro-ma-TO-sis) is a disease in which too much iron builds up in your body (iron overload). Iron is a mineral found in many foods.

Too much iron is toxic to your body. It can poison your organs and cause organ failure. In hemochromatosis, iron can build up in most of your body's organs, but especially in the liver, heart, and pancreas.

Too much iron in the liver can cause an enlarged liver, liver failure, liver cancer, or cirrhosis (sir-RO-sis). Cirrhosis is scarring of the liver, which causes the organ to not work well.

Too much iron in the heart can cause irregular heartbeats called arrhythmias (ah-RITH-me-ahs) and heart failure. Too much iron in the pancreas can lead to diabetesexternal link icon.

If hemochromatosis isn't treated, it may even cause death.


The two types of hemochromatosis are primary and secondary. Primary hemochromatosis is caused by a defect in the genes that control how much iron you absorb from food. Secondary hemochromatosis usually is the result of another disease or condition that causes iron overload.

Most people who have primary hemochromatosis inherit it from their parents. If you inherit two hemochromatosis genes—one from each parent—you're at risk for iron overload and signs and symptoms of the disease. The two faulty genes cause your body to absorb more iron than usual from the foods you eat.

Hemochromatosis is one of the most common genetic disorders in the United States. However, not everyone who has hemochromatosis has signs or symptoms of the disease.

Estimates of how many people develop signs and symptoms vary greatly. Some estimates suggest that as many as half of all people who have the disease don't have signs or symptoms.

The severity of hemochromatosis also varies. Some people don't have complications, even with high levels of iron in their bodies. Others have severe complications or die from the disease.

Certain factors can affect the severity of the disease. For example, a high intake of vitamin C can make hemochromatosis worse. This is because vitamin C helps your body absorb iron from food.

Alcohol use can worsen liver damage and cirrhosis caused by hemochromatosis. Conditions such as hepatitis also can further damage or weaken the liver.


The outlook for people who have hemochromatosis largely depends on how much organ damage they have at the time of diagnosis. Early diagnosis and treatment of the disease are important.

Treatment may help prevent, delay, or sometimes reverse complications of the disease. Treatment also may lead to better quality of life.

For people who are diagnosed and treated early, a normal lifespan is possible. If left untreated, hemochromatosis can lead to severe organ damage and even death.
Then, there is the following which suggests strongly that if Vitamin C makes you feel worse, you need medical tests and guidance:


Q. Orthodox medicine advises people with Hemochromatosis (congenital iron overload in tissues) to avoid vitamin C? What is the foundation's opinion?

The foundation understands that vitamin C facilitates iron absorption, but according to our advisors, it also helps to regulate unbound Iron out of the body and might be a good treatment for this condition. People with hemochromatosis can take steps to reduce iron in the digestive tract at the same time they are taking vitamin C orally.

A., Opinion of Robert Cathcart, III, MD (orthomed.com) :

My clinical experience would indicate that vitamin C increases iron absorption when iron is needed. It seems to increase excretion of iron when there is an excessive amount of iron. Therefore, vitamin C might be a good treatment of hemochromatosis.

This theoretical difficulty concerning C is typical of how the orthodoxy will expand a theory into a fact without any evidence.


A. Selva Kumar, MD opinion

I have managed many cases of iron overload because I see many Thallasaemia trait cases where the older patients usually have anemia but high ferritin levels. I continue giving 30 grams sodium ascorbate infusion weekly or biweekly for their chronic conditions, yet their ferritin DID NOT INCREASE and you see improvement in their anemia, with added folic, vitamin E and oral vitamin c at 3 to 6 grams per day.

One example is my nurse 86 years mother with ischemic heart and heart valve defect, I give her same IV vitamin C over the last two years, still well, her ferritin remains below 300 mg/dl .

Quite a number of 'heart patient' have elevated ferritin levels unless we check for it.

My experience with ferritin is in cancer patients, those with high baseline ferritin and IV vitamin C given (up to 120 grams per day) if the ferritin increases, the patient usually succumbed to their cancer, this is true for those with chemo or radiation.

I read a very good article on haemachromatosis and I will forward to you because that article made me decide to continue high oral and injection vitamin c despite the orthodox advice.

I give advice to those patients, avoid high iron containing diet and take oral vitamin C separately from food.

Dr Mercola also wrote a good article on iron, he believes in giving phytates to reduce absortion.

dr selva


A., Thomas E. Levy, MD, JD opinion

I cover this issue on pages 394 to 398 of my book VITAMIN C, INFECTIOUS DISEASES AND TOXINS. It's not as clear-cut as other issues, but high-dose vitamin C over the long run is probably as good for hemochromatosis as it is for other conditions.

Tom Levy

Note: There are other prudent approaches to reducing Iron overload according to health reporter and author Bill Sardi:

"The control and removal (chelation) of excess iron in the body is also important to remove the primary rusting agent in the the body that has the potential, when released from binding proteins, to damage tissues and DNA [Mutation Researdh 519: 151, 2002] Iron-binding nutrients knows as bioflavonids (citrus, quercetin, cranberry, bluebery, milk thistle) and from whole grains (IP6 rice bran extract) bind and remove iron effiecntly". - Bill Sardi, The New Truth About Vitamins & Minerals, Here & Now Books, 2003. Pg 24.


Q. My First Case of Generalised Urticaria after IV vit-C Slow Bolus!
Sent: Tuesday, December 02, 2003 4:34 PM

Dear Sirs:

Yesterday was a bad day. At 1430 hours a 30-year-old man (security guard) came with features of high fever for three days with chills and rigors. He had seen a day earlier another doctor who prescribe paracetamol, amoxycillin, buscopan tablets, to no relief.

I saw him, appeared toxic, flushed face, Bp 120/90, pulse 110,t emperature 38'Celsius, complaining feeling cold, severe headache and mild flu. Hess test is negative, no petechie of Dengue (there is dengue cases here)

I prepared a 15 gram sodium ascorbate in 60 cc syringe and given slowly intravenously but after nearly 10 grams(40cc), he complained of generalized itching with hives developing and immediately I gave intramuscular 10 mg chlorpheniramine and oral cetirizine 10 mg. I observed him and did not continue the remaining IV C. Then he complained of severe chills and after another 15 mins the ictchiness recurs and another 5 mg chlorpheniramine was given IM. He was really having rigors with 'goose pimples'! I kept observing him nearly 45 minutes in my consultation room before referring him to hospital but prescribe oral ascorbate powder for him.

I was not keen to give any adrenaline because he was not coughing/breathless and no wheezing or rhonchi noted and ictchiness got better after the chlorpheniramine. I also withheld any steroids in case this was a viral condition.

I was kind of 'jolted' by this event because I have been giving IV C bolus everday, sometimes twice a day and also apart from IVC infusions. I have no explanation for the above.

I felt close to nearly using steroids and or adrenaline!

My earlier one and only allergy is a 78-year-old female with hypothyroidism, I give 30 grams sodium ascorbate and oral antihistamine prior to infusion, she gets slight itchiness midway through the drip but tolerable. I still give her oral C and almost monthly IV C infusion. Once,s he had a fall with ankle sprain and I notice if a IV C infusion is given on consecutive days, her itchiness/allergy is less (I gave her 5 I VC infusion over 10 days)

I did not give IVC infusion to the man because his medical billing is limited.

I would appreciate any advice???

Though I was slightly 'shaken' but this kind of incidence is very rare.

My IVC bolus is pure sodium ascorbate powder dissolves in sterile water prior to injection.



From: Thomas E. Levy, MD

Subject: Re: My First Case of Generalised urticaria after IVC slow bolus! >Date: Tue, 2 Dec 2003 20:15:45 -0700

Dr. S.

Your patient sounds sick enough to conclude that he had a very high titer of virus in his body. While it is not very common, there are times when a reaction like the one you described occurs. I think one of three explanations accounts for the reaction.

#1, When the vitamin C is of corn origin, a few people have an allergic reaction to the corn, and something like beet origin vitamin C is needed. Using short-term steroids for such a situation is certainly reasonable. Also, adrenaline, if life-threatening bronchspasm begins to appear.

#2, There are people who have a Herxheimer-like reaction when a large amount of virus is killed quickly. Giving large amounts of fluid is good with even more vitamin C.

#3, few people, I believe, have massive detoxifications when given vitamin C. When the dose is low enough, the release of toxins is in excess of the ability of vitamin C to neutralize them. The answer is often more vitamin C, or increased oral supplementation for days to weeks before going back to the intravenous administrations.

With the hives being involved, the first allergic reaction is probably most likely.

Keep up the good work.

Best regards,

Dr. Levy
I couldn't get the paper but here's the abstract suggesting that this ferratin problem does show up in many AI conditions:

Autoimmun Rev. 2007 Aug;6(7):457-63. Epub 2007 Feb 16.
Ferritin in autoimmune diseases.
Zandman-Goddard G, Shoenfeld Y.

Department of Medicine C, Wolfson Medical Center, Israel.

Iron, an essential element for many important cellular functions in all living organisms, can catalyze the formation of potentially toxic free radicals. Excessive iron is sequestered by ferritin in a nontoxic and readily available form in a cell. Ferritin is composed of 24 subunits of different proportions of two functionally distinct subunits: ferritin H and L. The expression of ferritin is under delicate control and is regulated at both the transcriptional and post-transcriptional levels by iron, cytokines, hormones, and oxidative stress. Mutations in the ferritin gene cause the hereditary hyperferritinemia-cataract syndrome and neuroferritinopathy. Hyperferritinemia is associated with inflammation, infections, and malignancies. While elevated levels of ferritin are characteristic of adult-onset Still's disease and hemophagocytic syndrome, both associated with inflammation, it has scantly been evaluated in other autoimmune diseases. In this review, we describe ferritin structure and function, hyperferritinemia in disease states and in autoimmune diseases.
This talks about some really, really HIGH levels of Ferritin. But one wonders if the vitamin C my daughter was taking was accelerating an existing condition to the point where it showed up on the test results as it did? And if that is the case, were her ongoing, prior symptoms, related to a lower level of ferratin that accompanied a slow buildup of iron in tissues/organs that would later have caused serious problems?

Well, we don't know anything for sure yet. As I said, we'll be going to give blood as a test (if it makes one feel better, that's a definite clue) tomorrow and have another doctor's appointment scheduled to begin the process of genetic testing.

Diseases Associated with Markedly Elevated Ferritin Levels
Presenter: Reshma Marri: Loyola Univ Medical Ctr
Date: Sunday, November 11
Time: 9:00 AM - 6:00 PM
Location: Poster Hall (Hall B)

Session Title: Miscellaneous Rheumatic and Inflammatory Diseases: Periodic Fever Syndromes
Category: Miscellaneous Rheumatic and Inflammatory Diseases
adult-onset Still's disease, malignancy, Ferritin

Keywords: adult-onset Still's disease, malignancy


Adult onset Still’s disease (AOSD) is a rare form of inflammatory arthritis with inflammatory systemic disease of unknown etiology. It is a diagnosis of exclusion and can be a diagnostic challenge. A patient with suspected AOSD at our institution prompted a retrospective chart review of all patients with markedly elevated ferritin levels.

The patient, a 59 year old male with fever of at least one month who underwent an extensive negative evaluation for infection, malignancy, and other autoimmune etiologies was treated with high dose corticosteroids. A ferritin level at admission was 2200 ng/mL and rapidly rose to almost 50,000 ng/mL. Treatment for AOSD with IL-1 and IL-6 inhibition was unsuccessful and he died within one month from multi-organ failure. A bladder wall biopsy obtained just prior to death revealed an anaplastic large cell lymphoma.

{One wonders if they undertook to unload the iron by bleeding?}


In order to determine the association of autoimmune disease, including AOSD, with markedly elevated ferritin levels, in comparison to non-autoimmune diagnoses, we conducted a retrospective chart review of patients with elevated ferritins > 10,000 ng/mL seen at our institution from January 2000 to July 2011. Cases were divided into two subgroups, those with values between 10,000-15,000 and >15,000 ng/ml for analysis. The highest ferritin value was used when an individual subject had multiple values. There were 108 charts identified and reviewed for diagnoses at the time of the elevated ferritin level. Patients with either autoimmune disease, malignancies, liver disease, and/or infection were included in the analysis. Patients with hemoglobinopathies were excluded to avoid confounding of the ferritin levels by frequent blood transfusions. The remaining 88 cases were included for analysis.


Twenty six patients with ferritin levels between 10,000-15,000 ng/ml were identified. The mean age of patients in this subgroup was 46.6 years. Of these patients,

10/26 (38%) had elevated ferritin levels secondary to liver disease,
7/26 (27%) malignancy/infection,
6/26 (23%) malignancy alone,
1/26 (4%) autoimmune disease, and
1/26 (4%) infection and liver disease/infection respectively.

There were 62 patients with ferritins greater than 15,000 with a mean age of 44.3 years. Of these patients,

29/62 (47%) had liver disease,
9/62 (14%) malignancy,
7/62 (11%) autoimmune,
7/62 (11%) infection,
4/62 (6%) liver disease/infection,
4/62 (6%) malignancy/infection and 2/62 (3%) autoimmune/infection.


The observation that both ferritin groups include higher percentages of patients with liver disease and malignancy compared to autoimmune disease. Although not a part of the diagnostic criteria for AOSD, the presence of hyperferritinemia is commonly used to assist with diagnosis. These findings suggest that other diagnoses such as malignancies or liver disease should be considered in the differential diagnoses of markedly elevated ferritin levels. The diagnosis of AOSD is a diagnosis of exclusion and other underlying causes need to be ruled out.

Reshma Marri, Payal J. Patel, Amita Thakkar, Rochella A. Ostrowski, Eric McBride and Rodney Tehrani, Loyola Univ Medical Ctr, Maywood, IL

One naturally wonders if years of iron build-up in tissues could be behind these conditions, even those with those extremely high ferratin levels.

Notice that 11% of those with super high levels had auto-immune conditions. Notice also that they didn't seem to be very interested in exploring lower, but still abnormally high levels to find a correlation.
Towards explaining “unexplained hyperferritinemia”

Clara Camaschella and
Erika Poggiali

+ Vita-Salute San Raffaele University and IRCCS San Raffaele, Milan, Italy, E-mail: camaschella.clara@hsr.it

Ferritin has a central role in iron homeostasis since it binds and sequesters intracellular iron. It is a spheric shell with a central cavity where up to 4,500 atoms of iron are oxidized and stored. Ferritin is a multimer composed of 24 H (heavy) and L (light) subunits in variable proportions in different tissues. The two subunits are highly conserved during evolution, but only the H subunit has ferroxidase activity.1 Ferritin is also released in the circulation prevalently as L-ferritin or G-(glycosylated)-subunit through a largely unknown process. Since over recent years serum ferritin measurement has become a routine laboratory test, elevated serum ferritin is a common finding in clinical practice. High serum ferritin is found in a large spectrum of conditions both genetic and acquired, associated or not with iron overload. For this reason a precise diagnosis of hyperferritinemia requires a strategy that includes family and personal medical history, biochemical and eventually genetic or other tests, especially those related to tissue iron measurement.

It is well known that both acute and chronic inflammation, as occurring in infections, autoimmune disorders, chronic renal failure and also cancer – all conditions common in hospitalized patients – are associated with high ferritin levels. Another common process is cytolysis, an event that releases ferritin from the hepatocytes in patients with acute or chronic liver diseases. Very high levels of serum ferritin are found in Still’s disease, where hyperferritinemia is a marker of disease activity. It is biologically of interest that in this condition the glycosylated ferritin levels are lower (< 20%) than in normal subjects, whereas the glycosylated form represents 50–80% of the total ferritin.2 A simple determination of CRP is of help in excluding inflammation when the problem is not clinically evident. In addition, in inflammatory conditions high ferritin is not associated with increased saturation of transferrin that is usually normal or even decreased, according to the high hepcidin production which may lead to anemia of chronic disorders (ACD).3

<See link for Table 1.>

Genetic and acquired disorders associated with hyperferritinemia (not associated with anemia).

Elevated serum ferritin in association with high transferrin saturation (Table 1 and Figure 1) is usually a sign of iron overload. Increased body iron stores are found in the different forms of hereditary hemochromatosis (Table 1), where serum ferritin levels broadly parallel the entity of iron stores. Type 1 hemochromatosis is the most common form, prevalently expressed in middle age males. In most cases it is due to homozygous C282Y mutation of the HFE gene and in minority of patients to compound heterozygosity for both C282Y and H63D mutations or homozygosity for the latter mutation. Type 2 hemochromatosis, the juvenile form, are very rare due to mutations of hemojuvelin or of hepcidin and type 3 hemochromatosis which is characterized by mutations of TFR2. All these autosomal recessive disorders have inappropriately low hepcidin levels4 with consequent excessive iron release to the plasma from enterocytes and macrophages. For this reason transferrin saturation is high (>45%, but usually >60% up to 100% in the juvenile forms); its increase antedates the increase of serum ferritin and is associated with high levels of Non Transferrin Bound Iron (NTBI), the toxic moiety of iron, responsible for liver damage and eventually damage to the heart, pancreas and pituitary gland.

Very high levels of ferritin may be found in hemochromatosis type 4 or ferroportin disease which does not result from impaired hepcidin but rather from heterozygous mutations of the hepcidin receptor ferroportin.5 The disease is autosomal dominant and has a variable clinical phenotype. The true ferroportin disease (hemochromatosis type 4a in Table 1) is due to mutant proteins that are not correctly targeted to the cell surface and is characterized by macrophage iron accumulation, low/normal transferrin saturation and iron-restricted erythropoiesis.6 A second form (hemochromatosis type 4b), due to mutant ferroportins that reach the cell surface but are resistant to hepcidin-induced internalization,7 is characterized by hepatocyte iron accumulation and high transferrin saturation, as in hemochromatosis. The distinction is clinically relevant, because the true ferroportin disease seems not to be associated with clinical complications. These observations strengthen the relevance of assessing serum ferritin always in the context of transferrin saturation (Figure 1).

Ferritin is increased in iron overload secondary to chronic blood transfusions irrespective of the reason and also in the so called iron loading anemias, which include beta-thalassemia syndromes8 and congenital sideroblastic or dyserythropoietic anemias,9 characterized by high levels of ineffective erythropoiesis and low hepcidin production. All these conditions are usually well known from the patient’s history and may be diagnosed by specific tests. Several methods such as magnetic resonance imaging (MRI)10 or SQUID11 have become available to non-invasively assess hepatic iron concentration: however, serial ferritin determinations remain a useful guide to assess iron overload and to monitor iron chelation therapy in these patients.12

Diagnostic diagram of hyperferritinemia not associated with anemia or liver disorders.

Moderate increase of serum ferritin with normal/high transferrin saturation and mild/moderate liver iron accumulation may be common in chronic liver disorders, such as alcoholic liver disease and chronic viral hepatitis. These conditions require attention because iron may amplify the toxic effect of alcohol and viruses, accelerating the evolution towards fibrosis and cirrhosis. In porphyria cutanea tarda hyperferritinemia is a sign of iron overload (in some cases due to HFE mutations)13 and, like alcohol and chronic hepatitis, is a trigger of porphyria attacks.

In the metabolic syndrome (variable combination of hypertension, diabetes, hypertrigliceridemia, obesity, steatohepatitis or fatty liver) moderate elevation of ferritin is common, but usually ferritin levels are disproportionately high in comparison with iron stores,14 whereas transferrin saturation is not increased.

In recent years, new forms of inherited hyperferritinemia not associated with iron overload have been identified, adding new elements for differential diagnosis. A rare dominant trait is hereditary hyperferritinemia/cataract syndrome (HHCS), due to mutation in the IRE element of the 5’ untranslated region of L-ferritin mRNA.15–17 The mutation results in lack of repression of L-ferritin translation that becomes independent of iron availability and of iron regulatory protein regulation and occurs also in iron deficiency. Thus in HHCS, the high serum ferritin levels reflect an increased synthesis of the L-ferritin, but not of total body iron, since the L subunit does not participate in iron oxidation and storage. The condition is benign, the only clinical manifestation being early-onset bilateral cataract. Except for eye surgery, no treatment is required: the few patients who have been treated with phlebotomy developed anemia without changes in serum ferritin levels.15 {Obviously, this one does not respond to bleeding.}

In this issue of the journal, Kannengiesser et al.18 report a novel genetic dominant hyperferritinemia, that appears to have a benign course in the absence of iron overload (indicated as benign hyperferritinemia in Table 1 and Figure 1). These authors have collected a large number of samples from both familial (n=25) and isolated (n=66) subjects with unexplained hyperferritinemia. They defined as unexplained a condition of high serum ferritin (>200 ng/mL in women and >300 ng/mL in males) with transferrin saturation <45%, no excessive tissue iron (as determined by liver biopsy or MRI), serum iron <25 μmoles/L and absence of mutations in the IRE sequence of L-ferritin promoter. In this series of patients they found a single novel mutation (p.Thr30Ile) in the coding sequence of L-ferritin in half the familial and in a few of the isolated cases, but not in >500 normal controls. This finding is remarkable because mutations of L-ferritin are extremely rare and associated either with HHCS15–17 or a neurological disorder known as neuroferritinopathy.19 Although there is no proof that the mutation is the direct cause of the elevated ferritin levels (the mutation could still be only in disequilibrium with the causative one) the threonine residue at position 30, in the N-terminus of the A α-helix of L-ferritin is evolutionary conserved. In EBV-transformed cell lines from patients the ferritin content was normal, excluding an increased synthesis. The authors speculate that the mutated subunits probably do not have altered function, but since in the 8 patients whose sera was available the proportion of glycosylated L-ferritin was higher (90–100%) than normal, the abnormality could rely on an increased L-ferritin secretion, a process that should occur through the endoplasmic reticulum, but whose molecular mechanisms remain largely unknown. Ferritin levels typically fluctuate over time in these subjects, but at present no specific symptoms/abnormalities have been associated with this mutation. Much remains to be clarified and several other cases of hyperferritinemia still remain unexplained. However, another diagnostic option is now available for selected patients. Since a single mutation is responsible for the phenotype, a simple molecular test could easily be developed for the molecular diagnosis of the L-ferritin p.Thr30Ile mutation. Although no relevant clinical data seem to be associated with this sequence abnormality, the precise diagnosis of this new entity is relevant to reassure patients, and to avoid useless and expensive investigations.

Dr. Camaschella is a professor of internal medicine and Dr. Poggiali a fellow at the Vita-Salute San Raffaele University, Milan, Italy.
Chris Kresser (chriskresser.com) also has frequently written and talked about hemochromatosis in his blog and podcasts. If you find that you have it, his information may be helpful. Apparently it turns up quite a bit among his patients, who tend to be people that couldn't find help anywhere else.
Novel Biomarkers in Autoimmune Diseases
Prolactin, Ferritin, Vitamin D, and TPA Levels in Autoimmune Diseases

ABSTRACT: The development of autoimmune diseases may be influenced
by hormonal, immunomodulatory, and metabolic pathways.

Prolactin (PRL), ferritin, vitamin D, and the tumor marker tissue polypeptide antigen
(TPA) were measured in autoimmune diseases:

systemic lupus erythematosus (SLE),
systemic sclerosis (SSc),
rheumatoid arthritis (RA),
polymyositis (PM),
dermatomyositis (DM),
multiple sclerosis (MS),
autoimmune thyroid diseases, and antiphospholipid syndrome.

Hyperprolactinemia (HPRL) was detected in
24% of PM patients, in
21% of SLE patients, in
6.7% of MS patients,
6% of RA patients, and in
3% of SSc patients.

Hyperferritinemia was detected in 23% of SLE patients,
15% of DM patients,
8% of MS patients, and
4% of RA patients.

The patients had relatively low levels of 25 OH Vitamin D: the average results
(mean±SD) were between 9.3±4.4 to 13.7±7.1 ng/mL in the different
diseases, while the 25 OH Vitamin D concentrations less than 20 ng/mL
are regarded as deficient.

TPA levels were in the same range of the controls,
elevated only in SLE.

HPRL, hyperferritinemia, hypovitaminosis D, and TPA levels
did not correlate with SLE activity elevated levels of
rheumatoid factor or anti-CCP antibodies in RA.

HPRL, hyperferritinemia, and hypovitaminosis D have different immunological implications
in the pathogenesis of the autoimmune diseases.

Preventive treatment with vitamin D or therapy for HPRL with dopamine agonists, may be
considered in certain cases.

Hyperferritinemia may be used as an acutephase
reactant marker in autoimmune diseases mainly SLE. TPA may
be used to indicate the tendency for malignancies.


  • novel biomarkers in autoimmune diseases.pdf
    155.9 KB · Views: 7
Reading this have been very useful. Just a couple of weeks ago I met a girl with a very weird pain in her belly that no standard test or doctor was able to clarify or understand. Her mom was carrier of the gene, yet the daughter's genetic result showed that she was not a carrier. Yet her ferritin levels and other hemochromatosis parameters were high. It was weird and this info explains why!

From reading the above, it does look like they are discovering new genes and their disruption mechanisms like all the time! There are so many garden varieties that one wonders. It reminds me of gluten intolerance Vs celiac disease and how only if you have a teensy biopsy out of the vast universe that your gut is, then you are officially diagnosed.

So it strikes me that mainstream medicine might test just the basic genes, but not the ongoing discovered ones. The girl above probably was having health problems stemming from iron overload, yet her genetic test was negative. The mother on the other hand was not having significant health problems and yet she was a carrier.

That it probably stemmed from a surviving Celtic person in Northern Europe was interesting. Also that other ethnic people have it. The following is interesting too:

C282Y heterozygotes usually do not develop iron overload unless they have associated conditions, such as
environmental factors (alcohol, viruses, hepatic disease) or variant forms of other genes (see below).

Alternatively, chelation therapy might be considered in those cases with substantial parenchymal
iron overload and low tolerance of phlebotomy

Perhaps some people feel so much better after chelating "mercury" and other "heavy metals", perhaps they were chelating an iron overload in tissues?

multiple sequence variations in the recently identified genes involved in iron homeostasis are rare and do not appear to explain most of the variation in the penetrance of HFE hemochromatosis

In concordance with its dual function, hepcidin expression is modulated by systemic iron requirements and infectious and inflammatory stimuli

The importance of vitamin D in innate immunity has been highlighted by studies demonstrating that monocyte/macrophage responses to bacterial infections via Toll-like receptors (TLRs) are potentially stimulated by 25-hydroxyvitamin D (25(OH)D) following localised induction of both vitamin D receptor (VDR) and 1α-hydroxylase.[17]

It was the vitamin D receptor the one that some nasty bacteria messes up with in order to grow safely inside cells. Wonder if some viruses do the same thing.

Induction of IFNα from stimulation of TLRs by nucleic acid-containing immune complexes is thought to be one of the mechanisms by which patients with SLE have increased IFNα activity.[21] Supporting this hypothesis is evidence that activation of the IFNα pathway is associated with the presence of autoantibodies directed against DNA and RNA binding proteins.[22 23] Supporting this hypothesis is evidence that activation of the IFNα pathway is associated with the presence of autoantibodies directed against DNA and RNA binding proteins.[22 23]

A nucleic acid-containing immune complexes makes me thing of an immune system fighting a virus which has nucleic acid.

Interferon α (IFNα) has been shown to be a key cytokine in the pathogenesis of SLE. Numerous studies have confirmed the association between raised IFNα levels and increased disease activity in SLE

The hypothesis that vitamin D deficiency contributes to increased B cell activation in patients with SLE and increased production of autoantibodies, in particular those directed against nucleic acids, provides a mechanism for the association of vitamin D deficiency with increased IFNα activity (working hypothesis shown in figure 4). Nucleic acids contained within autoantibody immune complexes can activate TLRs, thus promoting IFNα production from plasmacytoid dendritic cells (pDCs) in patients with SLE.

This increase in autoantibody production, specifically of antibodies directed against self-nucleic acids, could lead to an increase in IFNα production by plasmacytoid dendritic cells via Toll-like receptor (TLR) signalling mediated by immune complexes.

These conditions require attention because iron [overload] may amplify the toxic effect of alcohol and viruses, accelerating the evolution towards fibrosis and cirrhosis.

Megan said:
Chris Kresser (chriskresser.com) also has frequently written and talked about hemochromatosis in his blog and podcasts. If you find that you have it, his information may be helpful. Apparently it turns up quite a bit among his patients, who tend to be people that couldn't find help anywhere else.

Thanks for the hint. The following is from a podcast transcript; I'm just including the part about hemochromatosis and iron loading in general:

Danny Roddy: Hello everyone, and welcome to the Healthy Skeptic Podcast. My name is Danny Roddy of DannyRoddy.com, and with me is Chris Kresser, health detective and owner of ChrisKresser.com, a blog challenging mainstream myths about nutrition and health. Chris, I’m extremely embarrassed, but yesterday was the first time I’ve ever given blood.

Chris Kresser: Congratulations! How’s your glucose tolerance and insulin sensitivity?

Danny Roddy: I don’t know. After a few more times, we’ll see how it goes. I didn’t have extremely high ferritin ever, but your conversation with Colpo was enough to get me in there to plan a few more blood draws.

Chris Kresser: So, yeah, for those of you who didn’t follow that on the web, I’ve been doing a lot of research lately on iron overload because strangely I seem to have attracted all of the patients in the world that have this condition! I mean, it’s crazy. I would say just — and you know, I haven’t actually calculated, but I’d say conservatively 30% of the people that I see — and you know, everybody that I see, everyone who comes through the door I do a comprehensive blood panel on, so it’s pretty good for collecting data — I’d say 30% of people have iron overload, and this means they’re storing excess amounts of iron. They either have elevated ferritin alone or elevated ferritin with increased serum iron, increased iron saturation, and then decreased total iron-binding capacity or unsaturated iron-binding capacity. And it’s true that ferritin is an acute phase reactant, like C-reactive protein, so it’s a protein that’s involved in the acute phase response, the inflammatory response, so sometimes elevated ferritin can be caused by inflammation, not iron overload, and it’s really important to distinguish between the two.

But anyways, I’ve got all these patients with iron overload, so I started to really do a lot of research, and what I noticed, too, in my practice was that most of these folks were really glucose intolerant. They really can’t tolerate much carbohydrate in their diet at all, and as soon as they start to increase their carbohydrate tolerance, they start gaining weight or they start feeling tired, have all the symptoms of insulin resistance and hyperglycemia.

So then I came across, randomly — I don’t even remember how — an article written by Anthony Colpo about how he reduced his ferritin levels because he was having glucose tolerance issues, and that completely reversed that problem. So I corresponded with him a bit, and we traded papers back and forth, and then I dove into the literature, and it was just fascinating what I learned.

There are all kinds of papers suggesting that even with people with relatively “normal” ferritin levels, meaning in the lab reference range, you know, levels of like 150 to 200, in these studies, what they did is through phlebotomy, which is the removal of blood, they would reduce the ferritin levels into the 25 to 50 range, which is the level of a premenopausal female. And these folks who were insulin resistant and had pretty significant glucose intolerance before that, that disappeared in the vast majority of the people when they could get their ferritin levels down that low.

Danny Roddy: Is the mechanism just oxidative stress, or how is it causing the glucose intolerance?

Chris Kresser: Yeah, iron is a pro-oxidant, so it does cause oxidative damage and inflammation, and it damages tissue and cells and organs and namely the pancreas and the pancreatic beta cells. So when you have too much iron, the iron damages the beta cells of the pancreas, it compromises insulin secretion, which would in turn decrease your carbohydrate tolerance.

And there are a bunch of other mechanisms, too. Iron overload is associated with — It’s one of those things like when you read the list of symptoms that can be caused by iron overload, it’s like, OK, well, maybe you should just make a list of symptoms that aren’t caused by iron overload. It’d be a lot easier! But some of the major ones and the ones that I’ve seen in my practice are hypogonadism, particularly in males, so it’s another hidden cause of low testosterone and issues with male hormone production because iron damages the pituitary and the whole hypothalamic-pituitary-adrenal axis. And then the pituitary can’t produce FSH and LH, and then that can’t stimulate the Sertoli cells and the Leydig cells to produce sperm and testosterone, so you get male infertility. It’s a huge cardiovascular disease risk, iron overload. It gets deposited in the liver, so it can cause impaired liver function and even lead to hepatitis or cirrhosis. It has pretty serious effects on brain and cognitive function and mood. It’s significantly associated with depression, muscle and joint pain. I mean, every tissue of the body is affected, so yeah, it’s a really big problem.

And interestingly enough, a lot of these papers that I was reading, these researchers are convinced that the difference between the heart disease risk between men and premenopausal women has nothing to do with hormone levels, and it’s actually related to iron status. And a little background on that is that, as I’m sure a lot of you know, it used to be thought that premenopausal women had such a lower risk for heart disease there was some protective effect of estrogen. And then we know that postmenopausal women have a more similar risk of heart disease to men, and it was thought that that’s because that protective effect of estrogen was no longer happening after menopause. And I’m sure a lot of you remember they tested this theory out — I think it was back in the ‘90s — with the hormone-replacement therapy trials, the HRT debacle. And the reason why it was a debacle is because they gave these menopausal women estrogen and they had to stop the trial because they were having twice the number of heart attacks instead of fewer.

So these researchers in these papers — And these are published in major peer-reviewed journals. It’s kind of amazing that I had never heard about it before. — These researchers believed that the difference is largely due to iron status because women, of course, menstruate every month, and they lose iron. Because the only two ways to get rid of iron when you have it in your body is through bleeding, so that could be menstruation or phlebotomy, which is the therapeutic removal of blood or donating blood like you did, Danny, or chelation, which is taking chemicals and, in some cases, some natural substances that bind to iron and remove it from the body. So premenopausal women are menstruating every month. They’re losing iron. Their ferritin levels tend to stay low, and their risk of heart disease is low, whereas men, of course, don’t lose blood like that unless they’re maybe mixed martial arts fighters or something like that!

Danny Roddy: Haha!

Chris Kresser: But their ferritin levels just gradually tend to increase with age because they just accumulate iron, and then they end up with higher ferritin levels, and higher ferritin levels are associated with increased risk for diabetes and cardiovascular disease. So I’m gonna write a series on it. It’s a fascinating topic.

I will say that one thing I don’t fully understand at this point is — You know, I always try to look at things from an evolutionary perspective, and I’m pretty sure that Grok wasn’t going down to donate blood every couple of months to keep his heart healthy and avoid diabetes. So I’m not sure why iron accumulation would be more of a problem now than it was then, especially considering the fact that, I mean, we can imagine that at least some of our ancestors were eating even more iron-rich foods like organ meats than we’re eating today. One possibility is that there is a genetic condition called hemochromatosis, where there’s a mutation of the HFE gene, and that causes overly aggressive iron storage. People who are homozygous for that mutation have really, really high levels of ferritin, like over 1000, and iron saturation of, like, 95%.

Danny Roddy: And they’re feeling really good.

Chris Kresser: Haha, yeah. I have a few patients in my practice with hemochromatosis actually, and one of them didn’t have a typical presentation. His ferritin levels, I think, were only 300 or 400, and that’s still actually in the lab range, so this is another example of where the lab ranges fail us, right? Because doctors saw that, told him it was no big deal. I saw it, thought it was a big deal!

Danny Roddy: Haha.

Chris Kresser: You know, we gave him the gene test, and he did, in fact, have hemochromatosis, and that’s a potentially life-threatening condition, so it’s really important to pay attention to this kind of stuff. But anyways, this genetic condition causes iron storage. Homozygous carriers usually become aware that they have it if they’re getting any kind of regular testing, but there are heterozygous carriers and then less common mutations of the gene that also probably cause increased iron storage but not to the degree that full-on hemochromatosis, you know, homozygous carriers have. I’m not familiar with the genetic history of this disease. In other words, I don’t know when hemochromatosis became a more common mutation. I do know that now it’s one of the most common genetic conditions in the Western world. In fact, I think it’s the most common. Between 1 in 200 and 1 in 300 people have it, so that’s not super common, but it’s not rare either.

Danny Roddy: I think we can blame Stop the Thyroid Madness for a ton of misinformation on this subject. I don’t know if you remember, but that website suggested that anybody exhibiting thyroid symptoms should try to get their ferritin, like, as high as possible.

Chris Kresser: Really?

Danny Roddy: I remember tons of people on that forum just trying to drive up their ferritin.

Chris Kresser: I never read that.

Danny Roddy: And I think one of the symptoms for iron overload is hypothyroidism.

Chris Kresser: You’ve got that right! Because like I said, if it affects the pituitary and the hypothalamus, which it does, then it’s gonna tank the thyroid because obviously the hypothalamus and the pituitary are the upstream regulatory glands that determine, you know, send the message to the thyroid gland of how much thyroid hormone to produce. So yeah, there’s a lot of misinformation out there on the Internet. It’s my nemesis in a way because, you know, a lot of patients come to me with all kinds of crazy ideas, and a lot of my work is sort of trying to re-educate them. And a lot of patients, on the other hand, are really smart and know a lot and have learned a ton from the Internet, and so it’s a mixed bag because it’s awesome that people can go and learn so much and educate themselves. And of course, that’s how I learned a lot of what I learned, so I’m talking out of both sides of my mouth here! But there is a danger in, you know, like you said, you read something on the Internet and you see a lot of other people doing it or following along, and you think it must be true because there are a lot of people following along, but unfortunately that’s not really a sufficient criterion to determine something’s validity.
Danny Roddy: You mean that’s not a logical fallacy?

Chris Kresser: I think Anatole France — I think that was his name — One of my favorite quotes is even if 50 million people say a stupid thing, it’s still a stupid thing.

Danny Roddy: Haha!

Chris Kresser: Words to live by!

Danny Roddy: On that note, do you want to get to our first question, Chris?

Chris Kresser: Yeah, let me just finish by saying before everyone runs out and starts donating blood every few weeks, it’s important to get a sense of whether your elevated ferritin is due to iron overload or because of inflammation, and also it’s important not to give blood more than every 55 or 60 days, especially if you’re active. Do not plan a high-altitude hike on the day that you’re giving blood because you’re gonna lose a fifth — They take a pint of blood, which is a lot, so it’s a fifth of your total blood volume. And if you’re sedentary, you might not notice it, but if you’re training or you’re active, I mean, they’re taking hemoglobin and red blood cells out. Hemoglobin delivers oxygen to the tissues. You need oxygen to produce ATP, which is the fundamental energy unit, energy currency of the body, so take it easy the day or two after you donate blood if you’re gonna do it. And I really recommend working under the supervision of a qualified practitioner with this because there are a lot of moving pieces, and if it is an inflammatory condition and you’re just removing blood month after month, hoping that the ferritin is gonna go down, that’s not gonna help.
Thanks for taking the time Laura for compiling it.

Considering how I'm doing on the keto diet there maybe exists a relation, at least lack of energy, fatigue, weakness and sometimes abdominal pain (which doesn't feel like coming from eating too much fat) and some improvements that I had at the beginning and are the opposite right now. I have to do another bloodtest in the next weeks and I maybe could ask to test for ferritin as well or some other tests. Another symptom that developed in the last weeks is feeling hungry most of the time.

But considering the idea of donating blood (which I'm not allowed to anyway) or just to make a test how I'm feeling afterwards does already turn me pale and turn my stomach.

Laura said:
Read, for example, this paper: http://www.clinchem.org/content/52/6/950.full.pdf
and then this one:

The second link requieres a log in.
Thanks for the information on this, Laura -- I had a neighbor with hemochromatosis who has to go in for monthly treatments. Maybe the old treatment of bloodletting wasn't as crazy as it sounds, but was just applied too broadly at the time? I hope that it's something that helps your daughter and helps her to start feeling better!

I just tried to do a little reading up on it, and it looks like there are some foods that are recommended that contain iron-binding elements, but at first glance several of these are evil or contrary to the ketogenic diet:


Tea and Coffee
According to the National Institutes of Health, teas like black tea and pekoe tea, have substances that bind to iron in the body, making the body unable to use the iron. Polyphenols, found in coffee, can also bind to iron, according to Dr. Srimathi Kannan of the American Dietetic Association. He states that black tea has the strongest ability to bind iron of all beverages, followed by coffee and then herbal teas like chamomile tea.

Whole Grains
Whole grains like whole wheat bread, brown rice, whole wheat pasta, whole wheat tortillas and spelt can also bind to iron in the body and block its absorption. The National Institutes of Health's Office of Dietary Supplements states that tannins are the compounds found in whole grains that bind to iron. Dr. Kannan states that the fiber in whole grains can bind to iron and cause the body to excrete the mineral.

Even though milk is full of calcium, vitamin D and vitamin A, it can decrease iron availability in the body. The National Anemia Action Council states that a component in milk can bind to iron. Therefore, it's important not to drink a glass of milk with an iron supplement or with an iron-rich food like beef or chicken. If you're trying to prevent or manage anemia, it's better to drink a glass of milk a few hours before taking iron or eating high-iron foods.

Phosphorus is a mineral found in nuts like almonds, walnuts and macadamia nuts. The form of phosphorus in nuts is called phytates. Dr. Kannan of the American Dietetic Association states that phytates are negatively charged, so they connect with positively charged iron ions and prevent the body from using iron effectively. Nuts can still be a part of a healthy diet, especially since they contain some iron and protein, but it's best to limit portion sizes of nuts and continue eating better sources of iron like meats and beans as well.


Hemoglobin is the iron-containing protein that carries oxygen, and your levels are below the desired amount. Yet, on the other hand you have Hemochromatosis, which is a condition where you have too much iron stored in the body. Normally, hemochromatosis is treated by avoiding iron-rich foods and periodic blood letting to remove excessive iron in the blood. However, the most common natural approach to raising hemoglobin levels is an iron-rich diet.

Hemochromatosis is most often not so much a problem of excessive iron as it is improper absorption and utilization of iron. While there are a number of natural items which can remove excess iron (such as cilantro, parsley and chlorella), the one I would look at is lactoferrin. Lactoferrin, found in raw milk, non-denatured whey, and colostrum milk and also sold as a supplement itself, modulates iron - binding and ridding excessive iron and making sure that needed iron gets to the right areas for proper metabolization.

Another area I would pay close attention to is your liver. People with hep-c generally have impaired livers and the liver is essential in the proper absorption and utilization of iron. Oleander extract, colloidal silver and several other items can be used in combination to correct hep-c and restore liver function.

However, things may not be quite that bad -- it looks like you might be able to take supplemental phytic acid and achieve the same effect you might otherwise be able to get with natural phytic acid from grains:


Dietary Iron Control

Various dietary practices can help control iron levels. In a relatively short period of time, dietary changes can result in anemia, iron overload or an ideal state of iron control. Anemia can be induced in about 120 days, while symptoms of iron overload can come on in just 60 days.

Humans absorb only a fraction of the iron they consume, but there are many controlling factors. [20] Iron absorption rates from food vary widely, from less than 1 percent to nearly 100 percent. [21] Cooks who use iron or stainless steel pots increase the amount of iron they consume. [22] Generally, iron in plant foods is not as well absorbed as iron from meat: Only 5 percent of iron in plant foods is available, vs. 30 to 50 percent of iron from meat. [23] Olive oil and spices such as anise, caraway, cumin, licorice and mint promote iron absorption, [24] while antacids, eggs and soy reduce availability. [25] Since dairy products contain lactoferrin, milk also inhibits the absorption of iron. [26] Moderate alcohol consumption is unlikely to pose a problem with iron absorption, but excessive amounts of alcohol is associated with iron overload, particularly in adult males. [27]

Vitamin C also increases iron absorption. [28] However, there is no evidence that vitamin C leads to iron overload. Thus vitamin C should not be avoided by meat-eaters for this reason, since studies show high-dose vitamin C supplements are associated with a decreased risk for heart disease, cancer, cataracts and other disorders. [29] A vegetarian diet does not generally cause iron-deficiency anemia because there is more vitamin C in plant-food diets, which enhances absorption. [30]

A 1982 human study was conducted to assess the effect of various drinks on iron absorption. A subject ate a standard meal of a hamburger, string beans, mashed potatoes and water. When green tea was drunk instead of water, iron absorption was reduced by 62 percent. Coffee reduced iron absorption by 35 percent, whereas orange juice (as a source of vitamin C) increased absorption by 85 percent. Contrary to other studies, milk and beer had no significant effect. [31]

Bioflavonoids (found in berries, coffee, green tea, pine bark, quercetin and the rind of citrus fruits, particularly blueberry, cranberry, elderberry and grape seed) and phytic acid (a component of whole grains and seeds such as sesame) bind to iron and other minerals in the gastric tract and help to limit iron availability. If bioflavonoids and phytic acid haven't bound to minerals in the digestive tract they will get into the bloodstream, where they can bind to free iron, acting as blood-cleansing iron chelators. Therefore, maximum iron chelation in the blood circulation is achieved when these iron binders are consumed apart from meals.

Phytic acid—also called inositol hexaphosphate, or IP6—is comprised of six phosphorus molecules and one molecule of inositol. It has been mistakenly described for decades as an "anti-nutrient" because it impairs mineral absorption. However, in the 1980s food biochemist Ernst Graf, Ph.D., began to tout phytic acid for its beneficial antioxidant properties achieved through mineral chelation. [32]

Phytic acid in foods or bran should be distinguished from supplemental phytic acid, which is derived from rice bran extract. In foods, phytic acid binds to iron and other minerals in the digestive tract and may interfere with mineral absorption. As a purified extract of rice bran, taken between meals so it will not bind to minerals in the digestive tract, phytic acid is readily absorbed into the bloodstream, where it acts as a potent mineral chelator. [33] Phytic acid binds to any free iron or other minerals (even heavy metals such as mercury, lead and cadmium) in the blood, which are then eliminated through the kidneys. Phytic acid removes only excess or unbound minerals, not mineral ions already attached to proteins.

Phytic acid is such a potent—but safe—iron and mineral chelator that it may someday replace intravenous chelation therapy such as the mineral-chelator EDTA or iron-binding drugs such as desferrioxamine (Desferal). Because of its ability to bind to iron and block iron-driven hydroxyl radical generation (water-based) as well as suppress lipid peroxidation (fat-based), phytic acid has been used successfully as an antioxidant food preservative. [34]

Phytic acid supplements should not be taken during pregnancy since the developing fetus requires minerals for proper development. Because aspirin causes a small loss of blood and consequently helps to control iron levels, the simultaneous use of phytic acid with a daily aspirin tablet is not advised. A three-month course of phytic acid should achieve adequate iron chelation, and prolonged daily supplementation may lead to iron-deficiency anemia. Anemic individuals who take phytic acid as a food supplement are likely to feel weak shortly after consumption, whereas iron-overloaded individuals are likely to feel increased energy.

For those at risk for iron overload, it may be wise to avoid iron in multivitamins and shun fortified foods that provide more than 25 percent of the recommended daily intake for iron. No doctor should prescribe iron tablets for patients who complain of fatigue without blood tests and a thorough health history. Iron-rich foods such as red meat and molasses may prevent anemia and build strength during the growing years but in adulthood may lead to iron overload among men and postmenopausal women. Those individuals who learn how to achieve iron balance will maintain the most desirable state of health throughout life.

I also ran across the following link for an ebook on treating hemochromatosis:


It has a hard-sell approach that's kind of a turn-off to me, but I don't know if the actual contents might be worth looking into or not.
Autoimmun Rev. 2007 Aug;6(7):457-63. Epub 2007 Feb 16.
Ferritin in autoimmune diseases.
Zandman-Goddard G, Shoenfeld Y.

Department of Medicine C, Wolfson Medical Center, Israel.

Iron, an essential element for many important cellular functions in all living organisms, can catalyze the formation of potentially toxic free radicals. Excessive iron is sequestered by ferritin in a nontoxic and readily available form in a cell. Ferritin is composed of 24 subunits of different proportions of two functionally distinct subunits: ferritin H and L. The expression of ferritin is under delicate control and is regulated at both the transcriptional and post-transcriptional levels by iron, cytokines, hormones, and oxidative stress. Mutations in the ferritin gene cause the hereditary hyperferritinemia-cataract syndrome and neuroferritinopathy. Hyperferritinemia is associated with inflammation, infections, and malignancies. While elevated levels of ferritin are characteristic of adult-onset Still's disease and hemophagocytic syndrome, both associated with inflammation, it has scantly been evaluated in other autoimmune diseases. In this review, we describe ferritin structure and function, hyperferritinemia in disease states and in autoimmune diseases.

Here are more quotes:

Ferritin is nature's unique and conserved approach to controlled, safe use of iron and oxygen, with protein
synthesis in animals adjusted by dual, genetic DNA and mRNA sequences that selectively respond to iron or
oxidant signals and link ferritin to proteins of iron, oxygen and antioxidant metabolism [1–3].

It is well established that elevated ferritin levels are found in adult Still's disease, but hyperferritinemia has been scantly investigated in other autoimmune diseases. The rationale for evaluating this protein in autoimmune
diseases derives from it being an acute phase reactant (APR), and hence increased during inflammation. APRs
have been found to be elevated and conducive of activity of disease, such as C-reactive protein (CRP) in rheumatoid arthritis. In SLE, other than an elevated erythrocyte sedimentation rate (ESR), APRs such as serum amyloid component P (SAP), C-reactive protein (CRP), and mannose binding lectin (MBL) {this reminded me of viruses and bacteria and how mannose is used for bladder infections to bind bugs and eliminate them through the urine} are not raised, indicating a possible mechanism of antibody production that blocks their function.


Ferritins share a unique protein cage structure that resembling spherical viruses that are preserved throughout species and permit storage of up to 4500 Fe (III) atoms. Polypeptide subunits of ferritin spontaneously fold into 4 helix bundles and assemble into hollow spheres with inner cavities, depending on whether there are 12 (mini-ferritins) or 24 (maxiferritins) subunits. When there are mini-ferritins, such as in bacteria, the catalytic site is created between 2 subunits in contrast to maxi-ferritins which are proprocessed within each subunit. Each apoferritin (iron-free ferritin) shell is assembled from 24 polypeptide chains of 2 species, the heavy subunit (H-subunit) and the light subunit (L-subunit). A single functional H gene and L gene have been identified on chromosome 11q23 and 19q13.3, respectively. H-ferritin plays the major role in rapid detoxification of iron and intracellular iron transport and is found in organs of low iron content including the heart and pancreas. The L-subunit is involved in iron nucleation, mineralization, and longterm storage and predominates in iron storage organs such as the liver and spleen.

Controlling iron/oxygen chemistry in biology depends on multiple genes, regulatory messenger RNA (mRNA) structures, signaling pathways and protein catalysts. Ferritin, a protein nanocage around an iron/oxy mineral,
centralizes the control. Complementary DNA (antioxidant responsive element–/Maf recognition element—ARE/
MARE) and mRNA (iron responsive element—IRE) responses regulate ferritin synthesis rates. Maxi-ferritins concentrate iron for the bio-synthesis of iron/heme proteins, trapping oxygen; bacterial mini-ferritins, DNA
protection during starvation proteins, reverse the substrate roles, destroying oxidants, trapping iron and protecting

The ability of cells to induce rapid ferritin synthesis prevents the effects of free radical damages to cellular components. Ferritin synthesis is regulated by intracellular iron at both the transcriptional and translational levels.[...]

In addition to iron, ferritin synthesis is regulated by cytokines at various levels (transcriptional, post-transcriptional,
and translational) during development, cellular differentiation, proliferation, and inflammation. The cellular response by cytokines to infection stimulates the expression of ferritin genes.[...]

Expression of ferritin is also regulated by hormones, growth factors, second messengers, and hypoxia–ischemia and hyperoxia. Both oxidants and anti-oxidant response inducers regulate H-ferritin gene transcription[...]

Lipopolysaccharide (LPS; endotoxin), a component of the outer membrane of gramnegative bacteria, elicits a variety of reactions that involve ferritin[...]

Thyroid hormone may regulate ferritin posttranscriptionally[...] In addition to thyroid hormone, insulin and IGF-1 have also been implicated in regulation of ferritin at the mRNA level.

Ferritin and inflammation/infection

Macrophage ferritin accumulates during inflammation, when serum iron decreases and iron in specific cells increases, leading to ferritin with more iron/protein cage. Pathogen ferritins are the mini-ferritins that protect
bacterial DNA when exposed to ferrous ions and hydrogen peroxide
in vitro and confer cellular resistance
to oxidative damage in vivo. During infection or inflammation, it is the relative “iron deficiency” created by the host redistribution of iron, with a deficit in serum and an increase in macrophages (the main stimulus for
siderophore production), synthesized in response to environmental iron deficiency and associated with virulence.

Ferritin and the immune system

Ferritin has been reported to exhibit different immunological activities including: binding to T lymphocytes and inhibition of E-rosette formation, a concanavalin A response [6], a source for iron to catalyze oxygen radicals
in the Haber–Weiss reaction, suppression of the delayed type of hypersensitivity to induce anergy [7], suppression
of antibody production by B lymphocytes [8], decreasing the phagocytosis of granulocytes [9], and regulating
granulomonocytopoiesis [9].

Altered ferritin levels and disease

Ferritin and iron homeostasis have been implicated in the pathogenesis of many diseases, including diseases
involved in iron acquisition, transport and storage (primary hemochromatosis) as well as in atherosclerosis
[5], Parkinson's disease [10], Alzheimer disease [11], and pulmonary disease
[12]. Genetic mutations of the ferritin IRE region as well as coding regions of ferritin cause some hereditary human diseases. Ferritin L IRE mutations cause the hereditary hyperferritinemia-cataract syndrome [13], which is an autosomal dominant disease characterized by elevated ferritin levels and early-onset bilateral cataracts. Neuroferritinopathy, a dominantly inherited movement disorder characterized by decreased levels of ferritin and abnormal deposition of ferritin and iron in the brain, is caused by a mutation in the C-terminus of the ferritin L gene [14]. Recently, a mutation of a hemochromatosis associated gene (HFE), C282Y, was associated with an increased risk of coronary artery disease and cardiovascular mortality [5,15].

Ferritin and malignancies

Early views of the relationship between ferritin and cancer stem from work demonstrating an increase in total ferritin as well as a shift toward acidic (H-rich) ferritins in the serum of patients with various malignancies. However, subsequent evaluations of ferritin levels in tumor tissue itself have revealed a complex, perhaps disease-specific picture: for example, in some cases such as colon cancer, testicular seminoma, and breast cancer, increases in ferritin in tumor tissue versus comparable normal tissue have been reported; in other cases, including liver cancer, a decrease in ferritin is seen. New forms of ferritin may be involved in certain situations. A novel isoform of ferritin was recently described that is elevated in the serum of patients with neoplastic breast disease as well as during pregnancy and HIV infection [4]. Elevated ferritin levels in the CSF indicate meningeal disease such as infection or meningeal spread in CNS tumor disease, but cannot distinguish between the two causes. CSF ferritin was measured in patients with benign inflammatory and non-inflammatory neurologic disorders and in patients with malignant disease with and without documented central nervous system (CNS) involvement. CSF ferritin levels were increased in the majority of patients with inflammatory neurologic disease and in patients with malignant involvement of the CNS, but not in patients with non-inflammatory neurologic disorders and in malignant disease without CNS involvement. These findings indicate that although the specificity of CSF ferritin measurement is limited, it is a highly sensitive test that may be useful in the initial evaluation of patients with malignant CNS involvement, and in assessing their response to therapy [16].

Hyperferritinemia in autoimmune diseases

[...]Rheumatoid arthritis (RA)

RA is an autoimmune disease involving predominantly the joints, associated with inflammation and elevated cytokine production of TNFα and IL-1α. Serum levels of ferritin do not differ from those of controls, but do fluctuate within the normal range during disease activity. Elevated serum ferritin in RA patients rather reflect total stores of body iron. High concentrations of ferritin are found in the synovial fluid and synovial cells of RA patients [22,23]. Hyperferritinemia was reported in patients with systemic juvenile rheumatoid arthritis and correlated
with disease activity and reduced steroid dosage [24]. In another study, the mean ferritin was higher in the patients with RA compared to controls. There were significant correlations between serum ferritin levels and disease activity based on the disease activity DAS28 score in RA patients [25].

Systemic lupus erythematosus (SLE)

SLE is a multi-systemic autoimmune disease manifested by excessive autoantibody production. While a diffuse inflammatory state is obvious, APRs are not elevated, indicating abnormal function of these proteins. High concentrations of ferritin were reported in certain manifestations of lupus including in the urine of patients with nephritis [26], in the pleural fluid [6], and in the CSF of patients with meningitis [6]. Four studies examined the relationship between serum ferritin levels and disease activity in patients with SLE. In one study, the relationship between serum ferritin, disease activity (utilizing the SLEDAI score), and following treatment was sought in 128 SLE patients compared to RA patients as controls. Serum levels of ferritin during the more active stage of SLE exceeded those of RA patients and patients at less active stages of SLE. There were no significant differences between RA patients and SLE patients with mild disease. Serum ferritin was elevated especially in serositis and hematologic manifestation. In this prospective study, changes in SLEDAI scores before and after treatment correlated significantly with serum ferritin levels and inversely to C3 and C4 levels [27]. In a similar study, serum ferritin levels in 72 SLE patients were significantly higher than RA patients.

There was a significant difference in ferritin levels before and after treatment. The levels of ferritin in SLE were correlated with SLEDAI scores [28]. In a third study, the clinical relevance of serum levels of ferritin in SLE patients vs. controls, the correlations between such levels and clinical disease activity, anti-DNA antibody titer, and serum levels of complement were assessed.

Thirty-six SLE patients were evaluated for hyperferritinemia, including 21 patients with active disease. The SLE patients exhibited higher serum levels of ferritin and lower serum levels of CRP than the RA patients. Serum levels of ferritin at the active stage of SLE exceeded those at the inactive stage. The levels of serum ferritin in SLE were positively correlated with the anti-DNA antibody titer and negatively correlated with CH50 values [6]. One study found contrasting results. The clinical history, SLEDAI, CRP and ferritin concentrations were analysed throughout the disease course of 10 SLE patients. During a mean follow-up of 4.8 years, 10 exacerbations occurred. Throughout the disease course, CRP and SLEDAI correlated positively in 5 patients, whereas the correlation between SLEDAI and ferritin was positive in 7 patients. CRP and ferritin levels remained normal during 5 exacerbations. From this investigation, it was concluded that despite severe disease activity, ferritin levels can remain well within the normal range, limiting its clinical usefulness as a marker for disease activity [29].

Multiple sclerosis (MS)

Over the last few years, increased evidence has supported the role of iron dysregulation in the pathogenesis of MS, as iron is essential for myelin formation and oxidative phosphorylation. MS and its animal model, experimental allergic encephalomyelitis (EAE), are autoimmune disorders resulting in demyelination in the CNS. Data from several biochemical and pharmacological studies indicate that free radicals participate in the pathogenesis of EAE, and iron has been implicated as the catalyst leading to their formation [30]. In one study, apoferritin was injected to EAE mice in order to increase plasma ferritin levels and to evaluate disease activity. Additional mice received systemic injections of iron, which induces ferritin synthesis, in order to test the effects of exogenous iron on the disease course. Although plasma levels of ferritin were found to be elevated in both apoferritin and iron-injected EAE mice, only apoferritin treatment resulted in a reduction in disease activity.

The suppressive effects of apoferritin administration suggest that the increase in endogenous ferritin levels that have been previously observed in the CSF of chronic progressive MS patients with active disease might be functioning to limit the severity and spread of tissue damage [31]. Delivery of iron to the brain traditionally has been considered the responsibility of transferring where transferrin receptors are located primarily within gray matter areas. Another report provided evidence of ferritin binding sites primarily in white matter tracts in the brain. In brain tissue from MS patients, the normal pattern of transferrin and ferritin binding distributions is disrupted. Ferritin binding is absent in the lesion itself and in the immediate periplaque region within the white matter but returns to normal as the distance from the lesion becomes greater. These data suggest loss of ferritin binding is involved in or is a consequence of demyelination associated with MS [32].

One study investigated the indices of iron metabolism in 27 MS patients. Ferritin levels were significantly elevated only in chronic progressive active (CP-A) patients. Patients of the CP group had significantly higher ferritin values than the relapsing–remitting (RR) patients. Hence, the increased serum ferritin levels in nonanaemic MS patients with active disease reflect the increased iron turnover [33]. In addition, ferritin levels were found to be significantly elevated in the CSF of CP-A MS patients compared to levels in normal individuals. Both ferritin and transferrin levels were elevated in patients that had high CSF IgG values but not in patients with a high IgG index. Since ferritin binds iron, the increase of CSF ferritin levels in CP MS patients could be a defense mechanism to protect against iron induced oxidative injury [34].


Hormonal pathways are involved in ferritin regulation. Thyroid hormone induce ferritin expression and hence hyperferritinemia could be expected in inflammatory thyroid disease. In one study, elevated ferritin levels in patients with subacute thyroiditis correlated with disease activity and decreased following steroid therapy. These levels were higher when compared to patients with Graves' disease and Hashimoto's thyroiditis. Elevated serum ferritin concentration significantly declined with treatment by either aspirin or prednisolone [35].



Perturbations in ferritin function are not only detrimental for iron homeostasis, but can lead to disease states by mechanisms of inflammation, infection, injury, and repair. Ferritin has been implicated in various diseases and may be important in autoimmune conditions. Hyperferritinemia is present in active SLE, RA, and may play a role in MS. Further investigation into the mechamechanisms of ferritin in this group of diseases is warranted.

Take-home messages

• Controlling iron/oxygen chemistry in biology depends on multiple genes, regulatory messenger RNA (mRNA)
structures, signaling pathways and protein catalysts.

• Ferritin synthesis is regulated by cytokines (TNFα and IL-1α) at various levels (transcriptional, post-transcriptional,
and translational) during development, cellular differentiation, proliferation, and inflammation. The cellular response by cytokines to infection stimulates the expression of ferritin genes.

• Ferritin has been reported to exhibit different immunological activities including binding to T lymphocytes, suppression of the delayed type of hypersensitivity, suppression of antibody production by B lymphocytes, and decreased phagocytosis of granulocytes.

• Ferritin and iron homeostasis have been implicated in the pathogenesis of many diseases, including diseases
involved in iron acquisition, transport and storage (primary hemochromatosis) as well as in atherosclerosis, Parkinson's disease, Alzheimer disease, and restless leg syndrome.

• Mutations in the ferritin gene cause the hereditary hyperferritinemia-cataract syndrome and neuroferritinopathy.

Hyperferritinemia is associated with inflammation, infections, and malignancies.

• Thyroid hormone, insulin and insulin growth factor-1 have also been implicated in regulation of ferritin at
the mRNA level.

Hyperferritinemia in SLE correlates with disease activity.

• Some evidence points to the importance of hyperferritinemia in RA, MS, and thyroiditis, but further investigations are required including revelation of mechanisms.

I quoted almost the entire article! References and the rest on the attachment.


  • ferritin in autoimmune diseases.pdf
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I found the following, hope it helps:


Targeted Nutritional Strategies

Several dietary constituents have been investigated for their ability to treat iron overload. They work by either reducing or inhibiting iron absorption from the gut, or binding excess iron in the blood and tissues to help draw it out of the body. Additionally, the significant contribution of free radical damage to the progression of iron-overload associated diseases suggests a role for increasing antioxidant consumption.

Lactoferrin. Lactoferrin is an iron-binding protein analogous to the iron transporter transferrin; it binds and sequesters iron in areas outside of the bloodstream such as the mucous membranes, gastrointestinal tract, and reproductive tissues (Jiang 2011). It is present at high concentrations in milk, and is secreted by immune cells (neutrophils) as an antibacterial compound at sites of infection or inflammation (Paesano 2009; Brock 2012).

The antimicrobial effects of lactoferrin are attributed to its ability to deprive pathogenic microorganisms of the iron needed for growth (Brock 2012). Experiments also suggest lactoferrin may have antioxidant and anti-inflammatory properties, and may influence the expression of inflammatory genes (Scarino 2007; Paesano 2009; Mulder 2008). Evidence suggests low-iron apolactoferrin may be protective against iron-mediated free radical damage; it reduced iron-catalyzed formation of hydroxyl radicals in vitro (Baldwin 1984).

Polyphenols. Polyphenols such as chlorogenic acid (Kono 1998), quercetin, rutin, chrysin (Guo 2007), punicalagins (from pomegranate) (Kulkarni 2007), and proanthocyanidins (from cranberry) have been shown to bind iron in vitro (Lin 2011). In an in vitro binding study of 26 flavonoids (a type of polyphenol) isolated from a variety of sources (including tea catechins, hesperidin, naringenin, and diosmin), several were nearly as effective as desferoxamine at chelating ferrous iron when supplied at a 10:1 flavonoid/iron ratio. When supplied at a 1:1 ratio, quercetin, myrcetin, and baicalein (a flavonoid from skullcap) continued to chelate iron with the same efficiency as desferoxamine (Mladěnka 2011). As antioxidants, polyphenols may also reduce iron-catalyzed free-radical generation (Minakata 2011).

In a mouse model of iron overload (over 2,000 mg iron/g of liver weight), both quercetin and baicalin (fed as 1% of water, which is roughly equivalent to 15 grams for a 70 kg human) reduced iron-induced lipid peroxidation and protein oxidation in the liver, decreased liver iron stores as well as serum ferritin, and increased fecal excretion of iron (Zhang 2006). Clinical studies are necessary to confirm polyphenol’s effect(s) in humans.

Pectin. Pectin is an indigestible fiber that binds tightly to non-heme iron, thus interfering with its absorption. In a small study of 13 patients with idiopathic hemochromatosis (conducted before the genetics of hemochromatosis had been discovered), iron absorption decreased by nearly half following a loading dose of 9 grams/m2 of pectin (about 15 grams for the average adult). Cellulose fiber had no effect on iron binding (Monnier 1980).

Milk Thistle. Milk thistle and its flavonoid constituent (i.e., silymarin) have iron chelation and hydroxyl radial quenching properties (Borsari 2001; Abenavoli 2010). In HFE hemochromatosis patients, 140 mg of silybin (the main component of silymarin) taken with a test meal containing about 14 mg of non-heme iron reduced iron absorption by over 40% (Hutchinson 2010). When combined with soy phosphatidylcholine, silybin treatment for 12 weeks demonstrated a modest (13%) reduction in serum ferritin (indicative of reduced total body iron stores) in patients with chronic hepatitis C (Bares 2008). When combined with the injectable iron chelator desferoxamine, silymarin resulted in more effective reductions in serum ferritin than desferoxamine alone in patients with β-thalassemia (Gharagozloo 2009).

Curcumin. Curcuminoids, which are derived from the spice turmeric, are antioxidants and iron chelators. In experimental models, they have been shown to reduce iron-catalyzed oxidative damage of DNA (García 2012), liver damage associated with iron-associated lipid peroxidation (Reddy 1996), and free-radical damage due to iron in amyloid plaques characteristic of Alzheimer’s disease (Atamna 2006). In β-thalassemic mice, curcumin bound iron in the blood reduced cardiac iron deposits in mice fed a high-iron diet (Thephinlap 2011), and reduced iron-associated lipid peroxidation when combined with the IV chelator deferiprone (Thephinlap 2009). The iron chelation effects of curcumin in the liver depend upon total iron intake. At low dietary iron concentrations, curcumin demonstrated a significant reduction in transferrin saturation and plasma iron in mice given curcumin as 2% of their diet (Jiao 2009). Mice on high iron diets, however, saw significant decreases in liver ferritin (indicative of a decrease in iron storage capacity), but no changes in total plasma iron or transferrin saturation when given curcumin as 2% of their diet (Jiao 2006; Jiao 2009).

Green tea. Green tea catechins are potent antioxidants that demonstrate an iron chelating activity similar to the injectable chelator desferoxamine in test tube studies (Mandel 2006). The addition of green tea extract with a high epigallocatechin gallate (EGCG) content to blood samples from β-thalassemia patients rapidly chelated non-transferrin bound iron, and modestly reduced markers of lipid peroxidation (Srichairatanakool 2006). The ability of green tea catechins to cross the blood-brain barrier implicates them as possible agents for the chelation of abnormal iron deposits characteristic of several neurodegenerative disorders (Mandel 2006). Studies examining the effect(s) of green tea consumption on iron status in humans are conflicting. Several studies have shown no association between tea consumption and iron absorption, serum ferritin, or hemoglobin levels in individuals with adequate iron intake (Mennen 2007; Temme 2002; Cheng 2009). However, two studies did show reductions in serum ferritin and iron absorption with high consumption levels of green tea (Imai 1995) and green tea extract (Samman 2001) respectively.

Alpha lipoic acid. Alpha lipoic acid is an important antioxidant and enzyme co-factor. In cell culture, alpha-lipoic acid (in its reduced form, dihydrolipoic acid) protects neurons against oxidative damage catalyzed by iron or Alzheimer’s beta amyloid (Lovell 2003). In a preclinical trial, R-alpha-lipoic acid (R-LA) was fed to older rats with age-related accumulation of iron in the cerebral cortex. Following 2 weeks of R-LA supplementation, iron levels dropped to those indicative of younger rats (Suh 2005).

Carnitine. Carnitine is an internal shuttle that helps move fatty acids into the mitochondria for conversion into energy. Carnitine esters (acetyl-L-carnitine and propionyl-L-carnitine) are derivatives, which may have additional antioxidant activities that confer advantages over carnitine alone (Mingorance 2011). When combined with alpha lipoic acid, acetyl-L-carnitine attenuated the production of free radicals in cultures of iron-overloaded human fibroblasts (Lal 2008). In test tube studies, propionyl-L-carnitine inhibits superoxide radicals, and reduces lipid peroxidation catalyzed by hydrogen peroxide (Vanella 2000). It is also proposed that propionyl-L-carnitine can reduce the production of hydroxyl radicals generated by iron, because of its iron-chelating activity (Reznick 1992).
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