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Negative Health Effects of High Iron & Associated Diseases

Written by Maja Stanojevic, MD | Last updated:
Nattha Wannissorn
Puya Yazdi
Medically reviewed by
Nattha Wannissorn, PhD, Puya Yazdi, MD | Written by Maja Stanojevic, MD | Last updated:
Iron containing foods

Excess iron is associated with inflammation and several other health problems. Read this post to learn more about the negative health effects of high iron and conditions associated with iron overload.

Iron Overload

Lab Cutoffs for Iron Overload

Most labs consider blood ferritin levels greater than 150 – 200 ng/mL in women and greater than 400 ng/mL in men to be abnormal and indicative of excess iron stores (in the absence of chronic illness and inflammatory disorders) [1].

Additionally, transferrin saturation values above 55 – 60% may be indicative of iron overload [2].

If your ferritin or transferrin is high, work with your doctor to find the cause. Your doctor will interpret your results, taking into account your medical history, symptoms, and other test results.

Iron Overload from High Iron Intake

The risk of iron overload from dietary sources in adults with normal gut function is negligible. A tolerable upper intake level of iron is 40 mg/day per kg body weight for infants and children age 13, and 45 mg/day for people aged 14 and older [3, 4].

Iron intake without food can cause gastric upset, constipation, nausea, abdominal pain, vomiting, and faintness. Stools often appear darker in color [5].

In severe cases, iron overdose can cause diarrhea, blood loss, hypovolemic shock, multiple organ dysfunctions, and death [6].

Why Excess Iron is Bad

Excess iron can accumulate in vital organs like the heart, liver, pancreas, and endocrine glands. This stimulates the formation of free radicals, which damage proteins, DNA, membranes, and can lead to cell death [7].

Studies suggest that left untreated, chronic iron overload raises the risk of liver disease, cancer, sexual dysfunction, arthritis, heart disease, eye disease, and diabetes [8].

Health Conditions That Can Cause Iron Overload

Conditions listed below can cause iron overload. But your iron may be high but that doesn’t mean you have any of these conditions. Work with your doctor or another health care professional to get an accurate diagnosis.

1) Genetic Disorders

Hereditary hemochromatosis is the most common genetic iron overload disorder. It’s caused by mutations in genes that affect hormones controlling iron levels such as ferroportin and hepcidin [9].

This disorder is characterized by increased absorption of dietary iron and its buildup in the heart, liver, pancreas, hormone-producing glands, tissue and joints, where it causes injury and organ damage [10].

Aceruloplasminemia is another disorder caused by mutations in the gene encoding ceruloplasmin (Cp), an enzyme involved in the loading of iron onto transferrin following its release from cells [11, 12].

Low blood ceruloplasmin levels lead to iron accumulation in neural and glial cells of the brain, pancreatic insulin-producing cells, and liver cells. This iron accumulation can cause retinal damage, diabetes, cerebellar ataxia, dementia, and neurological disease [11].

Hereditary atransferrinemia is a rare disorder characterized by extremely low blood transferrin levels. Transferrin depletion allows non-transferrin bound iron to accumulate in the liver and other organs in toxic levels. It also impairs red blood cell production because red blood cell production requires transferrin-bound iron [13].

2) Transfusional Siderosis

Frequent blood transfusions, commonly done for patients with sickle cell anemia, beta-thalassemia, and bone marrow failure, can lead to iron toxicity and chronic iron overload [14].

Each unit of transfused blood introduces around 200 – 250 mg of iron, which is substantially more than the amount of iron that is absorbed through the gut daily (1 – 2 mg).

At first, iron accumulates in macrophages and later in the liver, pancreas, and hormone-producing tissue, thereby increasing the risk of heart disease and other chronic diseases [14].

3) Liver Disease

Many studies have reported elevated blood levels of ferritin and iron in those with Hepatitis C virus infection [15, 16].

This is likely due to a prolonged inflammatory liver state, which can lead to the release of iron and ferritin from damaged liver cells [16].

Raised liver iron stores were observed in approximately one-third of adult non-alcoholic fatty liver disease patients [17].

Certain studies suggest that blood ferritin can be used as a predictor of disease severity and advanced liver tissue scarring in patients with nonalcoholic fatty liver disease [18].

Health Conditions Associated With Iron Overload

We will now discuss health conditions associated with iron overload.

Remember, just because your iron may be high, that doesn’t mean you have any of the conditions listed below.

4) Metabolic Syndrome

Metabolic syndrome is a group of conditions that often occur together, increasing the risk of diabetes and heart disease. You have metabolic syndrome if you have 3 or more of the following:

  • High blood pressure
  • High blood sugar
  • Excess body fat around the waist
  • High “bad” cholesterol or low “good” cholesterol
  • High triglycerides

Researchers have found a link between iron overload and several features and complications of metabolic syndrome, such as insulin resistance, high cholesterol, and liver damage, likely due to iron’s pro-oxidant activity [19].

5) Type 2 Diabetes

Increased dietary iron intake (especially from red meat) and body iron stores have been linked to the development of type 2 diabetes [20].

Iron-induced liver damage may have a role in initiating insulin resistance. The majority of those with iron overload are insulin resistant, suggesting that high liver iron stores and liver dysfunction may contribute to insulin resistance [21].

High levels of iron can also damage the pancreas and impair insulin secretory capacity [22].

6) Osteoporosis and Osteopenia

Research suggests that osteopenia and osteoporosis may be responsible for high death rates in patients with β-thalassemia major, a blood disorder and iron loading condition characterized by defective production of hemoglobin [23, 24, 25].

Osteoporosis is also a common complication of other iron loading conditions like sicklemia, African siderosis, hemochromatosis, alcoholism, and HIV infection likely due to the iron’s capacity to suppress bone growth and stimulate bone breakdown activity [25].

7) Heart Disease

Iron overload can cause heart damage, due to the buildup of iron in the heart muscle [26].

8) Impaired Immune Function

Decreasing the amount of iron available to bacteria is an important way of host defense [27, 28].

The availability of iron to invading pathogens is enhanced during iron overload, and people with excess iron, therefore, have an increased susceptibility to a variety of infectious diseases [29].

For example, studies have found that people with iron overload from hemochromatosis and thalassemia are more susceptible to infection with Yersinia spp., Listeria monocytogenes, and Vibrio vulnificus, among others [29].

Iron overload can alter immune system activity by [30]:

  • increase suppressor T-cell numbers and activity
  • decrease the numbers and activity of T-helper cells
  • impair the production of cytotoxic T cells and immunoglobulin (antibody) secretion

9) Cancer

Iron overload is a risk factor for cancer and liver cancer, in particular, attributed to the overproduction of reactive oxygen species and free radicals by excess free iron [31].

Iron may also accelerate tumor formation because it is a nutrient that promotes tumor cell growth [32].

Data from cell-based, animal and epidemiological studies link excess iron with multiple types of cancer including lung, breast, liver, gastrointestinal, and pancreatic cancer [32].

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