Evidence Based

Iron: Negative Health Effects of High Iron

Written by Maja Stanojevic, MD | Reviewed by Nattha Wannissorn, PhD | Last updated:

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Iron containing foods
When people go to their doctor to get their iron tested, almost always, the results are not scrutinized, even though we know that you can be healthier and live longer when your results lie within optimal ranges. When I used to go to doctors and tried to discuss my results, they had no clue what these meant from a health perspective. All they cared about was whether they could diagnose me with some disease.

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.

This post is a continuation of a 4 part series

Part 1: Iron Metabolism, Lab tests, Iron deficiency, Anemia and overload

Part 2: 47 Negative health effects of Iron Deficiency

Part 3: Iron Intake, Supplementation, and Ways to Increase or Decrease It

Part 4: Negative Health Effects of High Iron

Iron Overload

Lab Cutoffs for Iron Overload

Most labs consider blood ferritin levels greater than 200 ng/mL in women and greater than 300 ng/mL in men to be abnormal and indicative of excess iron stores (in the absence of inflammatory disorders) [1].

However, reference ranges are not the same as an optimal range. This is why iron even in the ‘normal’ range can be unhealthy and indicate that certain processes in the body aren’t optimal.

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

Iron Overload from High Iron Intake

The risk of iron overload from dietary sources in adults with normal gut function is negligible (R).

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 age 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 [R, 5].

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

High iron intake and/or stores are associated with increased risk of chronic diseases such as cardiovascular disease, diabetes and colon cancer [3].

Why Excess Iron is Bad

Excess iron leads to iron accumulation 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].

Left untreated, chronic iron overload raises the risk of liver disease, cancer, sexual dysfunction, arthritis, irregular heartbeat, heart failure, eye disease, diabetes, neurodegenerative diseases (Alzheimer’s, Parkinson’s, Huntington’s), and premature death [8].

Health Conditions and Diseases Associated with Iron Overload

1) Hereditary Hemochromatosis

Hemochromatosis is the most common genetic iron overload disorder caused by mutations in genes affecting hormones that control iron levels such as ferroportin and hepcidin [9].

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

2) Aceruloplasminemia

Aceruloplasminemia is a 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 [1112].

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].

3) Hypotransferrinemia/Atransferrinemia

Hypotransferrinemia is 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].

4) 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.

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].

5) Heart Disease and Hardening of the Arteries

High levels of ferritin are a risk factor for coronary heart disease, heart attack, and hardening of the arteries [15].

This may be because ferritin is not only an iron storage protein but also an inflammatory marker that increases in the presence of inflammation.

6) Metabolic Syndrome

Iron overload is associated with several metabolic syndrome complications such as insulin resistance, high cholesterol, and liver damage, likely due to its pro-oxidant activity [16].

7) Type 2 Diabetes

Increased dietary iron intake (especially from red meat) and body iron stores are linked to the development of type 2 diabetes [17].

Iron-induced liver damage may have a role in initiating insulin resistance. The majority of patients with iron overload are insulin resistant, suggesting that high liver iron stores and liver dysfunction may cause insulin resistance [18].

High levels of iron can also damage the pancreas and impair insulin secretory capacity [19].

8) Iron Overload Increases Cancer Risk

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 [20].

Iron may also accelerate tumor formation because it is a nutrient that promotes tumor cell growth [21].

Data from cell-based, animal and epidemiological studies link excess iron with multiple types of cancer including lung, breast, liver, gastrointestinal, and pancreatic cancer [21].

9) Elevated Iron Causes Osteoporosis and Osteopenia

Osteopenia and osteoporosis (OP) are responsible for high death rates in patients with β-thalassemia major (TM), a blood disorder and iron loading condition characterized by defective production of hemoglobin [222324].

Osteoporosis is also a common complication of other iron loading conditions like sicklemia, African siderosis, hemochromatosis, alcoholism, HIV infection, smoking, and menopause, likely due to the iron’s capacity to suppress bone growth and stimulate bone breakdown activity [24].

10) Iron is Elevated in Sarcopenia (muscle wasting)

Sarcopenia is defined as the involuntary decline of muscle mass and function that occurs during aging [25].

Many studies in aged animals and the elderly report an elevated iron status in the muscle [262728].

Raised serum ferritin levels are associated with an increased prevalence of sarcopenia in elderly women, likely due to iron-induced inflammation and oxidative stress, both of which are significant causes of muscle mass decline [2928].

11) Iron is Higher in People Infected With Hepatitis C virus

Many studies have reported elevated blood levels of ferritin and iron in patients with Hepatitis C virus infection [3031].

This is likely due to a prolonged inflammatory liver state, which can lead to the release of iron and ferritin from damaged liver cells [31].

12) Iron Store Maybe Elevated in Non-alcoholic Fatty Liver Disease (NAFLD)

Raised liver iron stores were observed in approximately one-third of adult non-alcoholic fatty liver disease patients [32].

Blood ferritin can be used as an independent predictor of disease severity and advanced liver tissue scarring in patients with nonalcoholic fatty liver disease [33].

13) Elevated Brain Iron May Cause Alzheimer’s and Other Neurodegenerative Diseases

Excessive iron deposition in the brain is consistently observed in Alzheimer’s Disease, Parkinson’s disease, multiple sclerosis, and other neurological diseases and contributes to the development and progression of these disorders [3435].

14) Iron Overload May Impair Immune Function

Iron overload without high iron intake can also be associated with changes in the immune system and increased infections [36].

Decreasing the amount of iron available to bacteria is an important way of host defense [37, 38, 37].

Iron overload can alter immune system activity by [39]:

  • 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

Irregular Iron Levels?

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4-Part Series

This post is a continuation of a 4 part series

Part 1: Iron Metabolism, Lab tests, Iron deficiency, Anemia and overload

Part 2: 47 Negative health effects of Iron Deficiency

Part 3: Iron Intake, Supplementation, and Ways to Increase or Decrease It

Part 4: Negative Health Effects of High Iron

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