Iron Overload - Symptoms, Causes, Dangers and Treatments

Iron overload is a condition in which too much iron circulates through your blood, giving rise to damaging free radicals. Here are some ways you can prevent it from happening.

Iron is a very critical element required in the body. One of the important functions of iron is that it is required in the synthesis of haemoglobin. But too much iron can lead to iron poisoning as well. 

Let's take a closer look at what causes iron overload, how it affects people, and how we can treat it.

In medicine, our goal is always to do as little harm as possible while trying to achieve maximum benefit to patients. In order to help us make decisions about treating certain diseases and conditions like hemochromatosis (a genetic disorder) or sickle-cell disease, doctors need accurate information. 

We know that when cells get damaged, they produce more free radical molecules than normal. These free radicals cause damage to surrounding tissue, including heart muscle, liver, pancreas, skin, joints, and brain function. 

When too many free radicals accumulate within tissues, though, it leads to organ disease and illness. 

What exactly is iron overload? How does it affect you? And finally, what treatments exist for this condition?

What Is Iron Overload?

Simply put, it's too much iron circulating throughout the body. The most common type of iron overload occurs due to hereditary factors, particularly thalassemia and hemochromatosis

Thalassemia, also known as beta-thalassemia major, results from mutations affecting genes responsible for making globin proteins. Normally, red blood cells contain two types of globin protein -- alpha globins and beta globins. 

People suffering from congenital forms of thalassemia lack functional beta-globin, leaving only alpha-globin. Since alpha-globin produces less oxygen-carrying capacity than beta-globin, their bodies become desperate for increased oxygen delivery via transfusions of packed red blood cells. 

Unfortunately, often, transfused red blood cells often end up carrying far too much iron, causing iron overload.

In hemochromatosis, the malfunctioning gene responsible for producing ferroportin is mutated, preventing the transfer of excess iron into intestinal enterocytes where it would normally be eliminated. Instead, the extra iron accumulates in macrophages, eventually leading to possible organ damage. 

Patients usually don't experience symptoms until middle age, after years of accumulating toxic levels of iron.

Although both inherited conditions occur frequently enough to warrant detailed research, environmental factors contribute to iron overload as well. Both hemodialysis and chronic kidney disease result in higher rates of iron accumulation. 

Similarly, pregnancy increases risk because of hormone changes that lower phytate levels. Phytic acid binds heavy metals like copper, zinc, lead, cadmium, and manganese, reducing absorption by 70 percent, and blood transfusions may further add to the load. 

How Does It Affect You?

As mentioned earlier, iron overload contributes to several different health problems. Chief among them is liver dysfunction. Excess iron damages the liver's ability to detoxify waste products created during metabolism. Liver inflammation may follow, resulting in cirrhosis and possibly also cancerous tumours. 

Other complications include diabetes, hypothyroidism, osteoporosis, arthritis, cardiomyopathy, heart failure, sleep apnea, infertility, depression, Alzheimer's disease, Parkinson's disease, dementia, erectile dysfunction, poor wound healing, high cholesterol, hypertension, obesity, gallstones, joint pain, shortness of breath, memory deficit, premature ageing, stroke, and infection susceptibility.

For children with sickle cell anaemia, iron overload can shorten their life span by 30 percent. Children develop painful episodes of bone marrow depletion that require regular blood transfusions to survive. Once the child grows past childhood, however, his or her lifespan significantly improves. 

Adult survivors face similar risks, especially since many choose to delay treatment until symptoms arise. Because iron deposition begins around puberty, women are especially vulnerable to developing iron overload later in life. 

Menopausal estrogen deficiency worsens menopausal symptoms like hot flushes, night sweats, and vaginal dryness. Oestrogen therapy helps restore ovaries' natural functions, increasing the excretion of accumulated iron. Progestogens used to suppress uterine bleeding associated with menses also encourage iron elimination.

Oral contraceptives containing drospirenone instead of older progestogens may enhance iron removal.

Despite improvements made to modern medical technology, iron overload remains difficult to manage. Treatment options range from dietary restrictions to medications, and controlled blood letting by a medical professional, i.e. phlebotomy.

Other methods include chelation therapy, whereby chemical compounds remove iron deposits before they build up sufficiently to create severe symptoms. 

Deferoxamine mesylate (Desogen), deferiprone (Ferriprox), and deferasirox (Exjade/Jadenu) are three examples of oral drugs designed to bind iron so that other organs can eliminate it. 

Others use hormones or enzymes to block the uptake of excessive iron directly. Zinc supplements promote the synthesis of metallothionein, an antioxidant protein capable of binding to metal ions and neutralising free radicals. 

Agents targeting interleukin 6 (IL-6) show promise in promoting mobilisation of reticuloendothelial system macrophages that carry excess iron away from target organs. Surgery removes fat depots to decrease the release of stored iron. 

Radiation therapy destroys malignant cells, releasing iron stores back into circulation. A final option uses stem cells taken from the patient himself to engraft new ones that produce anti-inflammatory cytokines that fight off attacks by scavengers looking to steal the iron's cargo.

While iron overload isn't considered a terminal disease, it still requires immediate attention. 

Read on for details on prevention and treatment strategies.

Treatment for Iron Overload

Unfortunately, diagnosing iron overload doesn't necessarily mean beginning treatment immediately. First, doctors must rule out other potential sources of elevated serum iron levels. 

Normal ranges vary depending upon gender, age, ethnicity, and lifestyle habits, but total serum iron should fall below 200 micrograms per deciliter (mcg/dl). 

Transferrin saturation (TSAT) values above 50 percent indicate iron overload. To calculate TSAT, multiply serum iron level by 100 and divide by transferrin concentration. 

Ferritinemia measurements above 1,000 nanograms per millilitre (ng/ml) confirm diagnosis. Elevated ferritin indicates genetic defects in the liver rather than true iron overload.

Once a proper diagnosis is established, management plans begin with dietary modifications. Dietary guidelines recommend limiting the consumption of meat, fish, shellfish, eggs, and milk products. 

Rather than eating meat daily, try replacing animal protein with beans, nuts, whole grains, and tofu. Eliminate or reduce caffeine, alcohol, tobacco, and refined sugar. Eat plenty of fruits and vegetables rich in vitamin C. 

Avoid consuming processed foods and limit salt intake. Finally, consume sufficient amounts of water each day. Water carries nutrients throughout the body, including iron, helping to maintain steady blood volume and avoid constipation.

After eliminating trigger foods, consult with a nutritionist who knows well about the correlation between nutrients and metabolism. He or she may work alongside your doctor to formulate a meal plan customised to meet individual needs. Most diets reduce calorie intake, typically by 500 calories per day. 

If chelating agents aren't effective enough to control iron burden, consider alternative therapies. Drugs such as deferoxamine mesylate (Dialyzable Copper), deferiprone (Ferriprox) and deferasirox (Shunterelle) improve absorption of essential minerals. 

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin E2, thereby diminishing gastrointestinal mucosal injury induced by iron. Pain relievers such as acetaminophen or tramadol allow patients to better tolerate the discomfort associated with indigestion. 

Sustained-release preparations provide extended relief. Desferrioxamine tablets (Feldene), delayed-release capsules (Deferactron), and slow-release injections (Imferon) represent additional approaches. 

While controversial, hyperbaric chamber therapy involves breathing pure nitrogen under pressure to maximise the efficiency of desaturation of erythrocyte ferrous ions.

BloodChelationFree-radicalsHaemoglobinHemochromatosisIronRbcThalassemiaTherapy

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