Ferritin: Cardiovascular, Liver Disease, Chronic Illness Help and Support

Ferritin Elevated

Elevated ferritin is associated with hypertension, cancer, cardiovascular heart disease and heart failure, diabetes, metabolic syndrome, cholesterol issues, elevated fasting insulin and blood glucose, insulin resistance and obesity.

One cause of elevated ferritin is a genetic mutations called hemochromatosis, usually seen in Caucasians with northern European ancestry.

Hemochromatosis is a serious condition with higher than normal ferritin levels.

Symptoms of this genetic condition can be abdominal pain, fatigue, skin darkening, joint pain, loss of body hair, decreased sexual desire, weight loss and general weakness.

Naturally, a person that does not have this inherited condition, but does have elevated ferritin, can experience these same symptoms.

Besides genetics, there are sets of populations which are predisposed to having elevated ferritin.

These are most commonly men over the age of 40 and women.

With women this primarily includes those in post-menopause, a history of hysterectomy and those taking the types of oral contraceptives which interrupt normal menstruation.

If we consider elevated ferritin as a disease, or at least a predisposing factor for developing a chronic disease, in the beginning the person is asymptomatic (no symptoms) yet at some point, when symptoms do appear, the diagnosis of elevated ferritin will unlikely be diagnosed, especially when the lab reference range is far too broad. More on this later.

The presenting symptoms and signs of elevated ferritin are often quite nonspecific and include chronic fatigue, endocrine-related symptoms such as amenorrhea, decreased libido, hypogonadism, impotence, infertility, hypothyroidism, hypopituitarism, and decreased adrenal function.

Other manifestations include elevated liver enzymes, cirrhosis, abdominal pain, skin discoloration (bronze coloration), arrhythmias, cardiac failure, osteoarthritis, osteoporosis, joint pain, hair loss, and enlarged liver.

How Ferritin is Harmful

Iron causes harm by catalyzing a reaction within the inner mitochondrial membrane. When iron reacts with hydrogen peroxide, hydroxyl free radicals are formed, which is a normal physiological process.

But when there’s too much iron, the increase if the hydroxyl free radical damages our mitochondrial DNA, and accelerate us towards degenerative diseases.

Lab Results for Ferritin

The reference range for ferritin can vary from one lab to another, but generally, 12 to 300 ng/ml of blood for males and 12 to 150 ng/mL for females is most common.

This range, especially the upper number, is far too broad for optimal health and the prevention of many chronic illnesses.

An ideal range, based on many published research papers, is somewhere between 30 and 60 ng/mL. You do not want to be below 20 ng/mL or above 80 ng/mL.

Alzheimer’s & Parkinson’s

Our brain and nervous systems are more susceptible to oxidative stress and inflammation.

It’s been known since the 1920s that neurodegenerative disease, including Alzheimer’s and Parkinson’s, is associated with increased iron deposition in the brain.

In 1924, a Parisian neurologist named Jean Lhermitte was among the first to show that certain regions of the brain became congested with abnormal amounts of iron in advanced Parkinson’s disease.

Thirty years later, in 1953, a physician named Louis Goodman demonstrated that the brains of patients with Alzheimer’s disease had markedly abnormal levels of iron deposited in the plaques and tangles that define the illness. Goodman’s work was largely forgotten for several decades, until a 1992 paper resurrected and confirmed his findings which kindled new interest.

Two years later the MRI was deployed to probe the association between iron and disease in living patients, confirming earlier autopsy findings that Alzheimer brains demonstrated significant aberrations in tissue iron.

By the mid 1990s, there was compelling evidence that Alzheimer’s and Parkinson’s disease involved some dysregulation of iron metabolism in the brain, but no one knew whether the relationship was the cause or consequence of the disease process.

A 1993 paper reported that iron promoted aggregation of amyloid-b, the major constituent of Alzheimer’s plaques.

In 1997, researchers found that the aberrant iron associated with Alzheimer’s plaques was highly reactive and able to freely generate toxic oxygen radicals (hydroxyl), which is associated with degeneration.

Perhaps most surprising was the discovery in 1999 that the pre-cursor to amyloid-b was under direct control by cellular iron levels: the more iron around, the more amyloid was produced.

By 2010, it had been shown that oxidative damage was one of the earliest detectable changes associated with Alzheimer’s and that reactive iron was present in the earliest stages of the disease.

And in 2015, a seven-year longitudinal study showed that cerebrospinal fluid ferritin levels were a strong predictor of cognitive decline and development of Alzheimer’s dementia.

Cardiovascular Ferritin

A Scandinavian study compared men who suffered a heart attack to men who didn’t, and found that elevated ferritin levels conferred a two- to threefold increase in heart attack risk.

Another study found that having a high ferritin level made a heart attack five times more likely than having a normal level.

A larger study of 2,000 Finnish men found that an elevated ferritin level increased the risk of heart attack twofold, and that every 1 percent increase in ferritin level conferred a further 4 percent increase in that risk.

A team of Canadian researchers compared blood iron levels to heart attack risk, and found that higher levels of ferritin conferred a twofold increased risk in men and a five-fold increased risk in women.

Diabetes & Ferritin

If cardiovascular disease is one point in iron’s web of disease, diabetes is another.

The first hint of a relationship between iron and diabetes came in the late 1980s, when researchers discovered that patients receiving regular blood transfusions (which contain quite a lot of iron) were at significantly increased risk of diabetes.

This new link between frequent transfusions and diabetes was indirect evidence that the iron itself may be the cause.

The next step was to mine existing data for associations between markers of iron status and diabetes. The first study to do so came out of Finland in 1997: Among 1,000 randomly selected Scandinavian men, ferritin emerged as a strong predictor of dysfunctional glucose metabolism.

In 1999, researchers found that an elevated ferritin level increased the odds of having diabetes five-fold in men and nearly four-fold in women, similar in magnitude to the association between obesity and diabetes.

Five years later, another study found that elevated ferritin roughly doubled the risk for metabolic syndrome, a condition that often leads to diabetes, hypertension, liver disease, and cardiovascular disease.

In 2015, among a sample of 6,000 people, those whose ferritin levels were in the highest 20 percent had 4 times greater odds of diabetes than those with ferritin levels in the lowest 20 percent.

Blood glucose levels, blood insulin levels, and insulin sensitivity all were raised with higher ferritin levels.

One of the first studies to use phlebotomy to examine the relationship between iron and diabetes was published in 1998. The authors found that among both healthy and diabetic subjects, phlebotomy improved insulin sensitivity and glucose metabolism.

A 2005 study found that regular blood donors exhibited lower iron stores and significantly greater insulin sensitivity than non-donors.

In 2012, researchers phlebotomized pre-diabetic volunteers until their ferritin levels dropped significantly, and found a marked subsequent improvement in their insulin sensitivity.

In that same year, a different group of scientists studied the effect of phlebotomy on several elements of metabolic syndrome, including glucose metabolism. They found that a single phlebotomy session was associated with improvement in blood pressure, fasting glucose, hemoglobin A1C (a marker for average glucose levels), and blood cholesterol six weeks later.

Cancer & Ferritin

Since the late 1950s we have known that injecting large doses of iron into lab animals was very likely to cause malignant tumors, but it wasn’t until the 1980s that scientists began looking for associations between iron and cancer in humans.

In 1985, Ernest Graf and John Eton proposed that differences in colon cancer rates among countries could be accounted for by the variation in the fiber content of local diets, which can in turn affect iron absorption.

The following year, Richard Stevens found that elevated ferritin was associated with triple the risk of death from cancer among a group of 20,000 Chinese men.

Two years later Stevens showed that American men who developed cancer had higher transferrin saturation and serum iron than men who didn’t.

In 1990, a large study of Swedish blood donors found that they were 20 percent less likely to get cancer than non-donor controls.

Four years later, a group of Finnish researchers found that elevated transferrin saturation among 40,000 Scandinavians conferred a threefold increase risk for colorectal cancer, and a 1.5-fold increased risk for lung cancer.

A host of research articles have been published since Graf and Eton’s first paper, and most have supported an association between iron and cancer, particularly colorectal cancer.

In 2001, a review of 33 publications investigating the link between iron and colorectal cancer found that more than 75 percent of them supported the relationship.

A 2004 study found an increased risk of death from cancer with rising serum iron and transferrin saturation. People with the highest levels were twice as likely to die from cancer than those with the lowest levels.

And in 2008, another study confirmed that Swedish blood donors had about a 30 percent decrease in cancer risk.

There are a few other lines of evidence that support the association between iron and cancer. People with the hemochromatosis gene mutation have an increased risk of developing colon and blood cancers.

Conversely, people diagnosed with breast, blood, and colorectal cancers are more than twice as likely to have this gene mutation than are healthy controls.

Liver Cancer

There are also a handful of interventional trials investigating the relationship between iron and cancer.

The first was published in 2007 by a group of Japanese scientists who had previously found that iron reduction via phlebotomy essentially normalized markers of liver injury in patients with hepatitis C.

Hepatocellular carcinoma (HCC) is a feared consequence of hepatitis C and cirrhosis, and they hypothesized that phlebotomy might also reduce the risk of developing this cancer.

The results were remarkable—at five years only 5.7 percent of patients in the phlebotomy group had developed HCC compared to 17.5 percent of controls. At 10 years the results were even more striking, with 8.6 percent of phlebotomized patients developing HCC compared to an astonishing 39 percent of controls.

The second study to investigate the effects of phlebotomy on cancer risk was published the following year by Leo Zacharski.

In a multi-center, randomized study originally designed to look at the effects of phlebotomy on vascular disease, patients allocated to the iron-reduction group were about 35 percent less likely to develop cancer after 4.5 years than controls. And among all patients who did develop cancer, those in the phlebotomy group were about 60 percent less likely to have died from it at the end of the follow-up period.

Iron overload also markedly increases the risk of cirrhosis and liver cancer once ferritin levels rise to greater than 1000 ng/mL, possibly 20-100 times the general population.

Colorectal Cancer

In 2001, a review of 33 publications investigating the link between iron and colorectal cancer found that more than 75 percent of them supported the relationship between high ferritin and the risk of colorectal cancer.

Chronic Disease & Ferritin

If so many studies seem to show a consistent association between iron levels and chronic disease, why isn’t more work being done to clarify this risk?

“It’s incredible that there is so much promising literature, and nobody, nobody is doing the clinical trials,” states Dr. Zacharski.

His perspective on why more trials haven’t been done is fascinating, and paralleled much of what other experts in the field said.

Molecular biology and targeted pharmaceuticals are hot, and lucrative, and iron is definitively not. “

Zacharski is convinced that iron overload is a huge common underlying cause of the chronic metabolic diseases that are sweeping Western countries.

He thinks that even subtly elevated iron levels can result in free radical formation, which then contributes to chronic inflammation and a wide variety of chronic diseases.

Ferritin & Lab Testing

Of course, the first step is to know if you have an elevated ferritin.

There are other useful labs as well including hemoglobin, GGT, and liver enzymes.

As mentioned previously, inflammation and a low grade systemic infection can cause elevated ferritin.

So the reduction of ferritin IS very important, but investigating the cause of inflammation, and knowing if there is an infection, are also important.

Blood inflammation markers, such as C-Reactive Protein and ESR (erythrocyte sedimentation rate), would help.

Most testing for a low-grade infection are useless, but looking at a tiny finger prick of blood under a darkfield microscope will expose them.

To determine if there is the hemochromatosis gene variant (282Y, H63D & S65C) is most often determined by a blood test, which is not inexpensive, and would likely never be done by a physician unless your ferritin level was greater than 1,000 ng/ml.

There is another options offered by Functional Genomic Analysis, which tests through either saliva or a cheek swab, all genetics including the above. This would provide a great deal of information that could be analyzed, not only for hemochromatosis, but many, many other susceptibilities to chronic diseases.

This test is $300 but does not include the time Dr. Haskell spends to explain the results and what can be used to address any SNP through supplements and nutrition.

Our suggestion is to first do the ferritin, and if elevated, to then consider other labs.

Medical Phlebotomy

Phlebotomy, or the removal of blood from the circulatory system, is one option for quickly reducing elevated Ferritin levels.

This can be done by donating blood through the Red Cross, though there are several restrictions around who can donate.

They also abide by a frequency of donation policy, often limiting phlebotomy to no more than every 6 weeks.

With each donation being approximately 450cc of blood, this typically reduces your ferritin by about 50 points.

If your ferritin is say 800 with an optimal being 60, this might take about 15 donation, and with their restrictions on frequency, this could take about a year and a half.

For those that are ineligible to donate and those who want to get their ferritin levels lowered more rapidly, we offer what is called a medical phlebotomy, meaning you can come to our office to have the blood removed.

Depending upon the health of the person, and a lab test for red cell count and hemoglobin, this phlebotomy can be done every 1-2 weeks, with random checks for red cells and hemoglobin to be sure you are not becoming anemic.

The charge for this phlebotomy is $50 and usually takes about a half-hour.

How To Reduce Iron

Our first recommendation is to become educated, to understand the perils of elevated ferritin and to become motivated to make changes in your eating habits.

We recommend two books; Dumping Iron and The Iron Time Bomb. Used copies can be found on Amazon.

Obviously, you need to reduce foods rich in iron, with red meat being at the top of the list.

Just google ‘foods high in iron’ and reduce these.

Do not drink alcohol with meals since this increases your absorption of iron. Apparently red wine is ok.

Ascorbic acid, vitamin C, capsules taken with meals will also increase iron absorption.

Buffered vitamin C (ascorbic acid and sodium ascorbate) taken away from meals is fine.

Drink green tea with meals.

Supplements

IP6, made from rice bran extract, is a phosphorylated form of inositol.

It has been shown in vitro to chelate, or remove, iron.

Oral administration of IP6 significantly decreased serum iron, total iron binding, serum ferritin and serum enzymes.

Histopathology of liver showed reduced hepatocellular necrosis, ballooning and inflammation, indicating the restoration of normal cellular integrity.

The extract of green tea, ECGC, is beneficial as well, likely best taken with meals.

There is an intravenous iron chelating therapy as well.