Isn’t Iron Ironic?

Iron Iron is a potentially toxic heavy metal, and excessive intake and storage can damage metabolism and promote inflammation, cancer, heart disease, Parkinson’s, Alzheimer’s, MS, diabetes and numerous other degenerative as well as infectious diseases.

“Iron may be carcinogenic in several ways: it catalyzes the formation of hydroxyl radicals which are cancer-causing agents, it suppresses host defenses allowing for proliferation of neoplastic cells and it acts as an essential nutrient for the proliferation of tumor cells.”

“…iron elevation is increasingly reported as a feature of Alzheimer’s disease…these data support…therapeutic strategies that lower brain iron, which have reported beneficial outcomes in Phase II trials of Alzheimer’s and Parkinson’s diseases”

“Iron is considered to play a key role in the development and progression of Multiple Sclerosis…iron that accumulates in myeloid cells…may contribute to chronic inflammation, oxidative stress and eventually neurodegeneration.”

Whilst it’s common to be told that iron insufficiency is at the heart of a variety of issues related to aging and disease, experimental evidence continues to show the opposite to be true, and when it comes to maintaining metabolic health, difficulty often lies in ensuring one does not consume and absorb too much.

“…data indicated that high body iron stores…are associated with an increased cancer risk. Other data shows an increased heart attack risk.”

“Iron has been shown to accumulate in deep gray matter structures in many forms of multiple sclerosis (MS)…The findings suggest that iron deposition is a pathological change that occurs early in the development of MS.”

Blood tests commonly used as evidence of ‘iron deficiency’ can be diagnostically misleading, and fail to accurately measure iron stored inside tissue, thereby not giving a real picture of iron status.

Tissue levels of iron can be predictive of disease outcomes and are an important benchmark for a genuine and accurate determination of metabolic health.

When stores are too high, iron tends to accumulate in the liver (as well as in other tissue including the brain and bone marrow) promoting stress and inflammation, interfering with a number of metabolic functions, encouraging cancer development.

“Liver is the major organ for iron storage and has the largest capacity to store excess iron. The measurement of hepatic iron concentration by liver biopsy is the most reliable means to assess body iron storage…”

“The accumulation of iron in the liver would strongly potentiate the development of hepatic tumours…”

Although serum ferritin tests can be somewhat predictive of high iron stores – especially when levels are on the extremely high end – it has been demonstrated that the ratio of ferritin/AST (aspartate transaminase) is an accurate predictor of liver iron concentration, and is therefore an easier way to determine whether there is iron overload, avoiding more invasive methods such as liver biopsy. Ferritin and transferrin measured together can also help to give a more reasonable picture of actual iron storage status.

“Elevated serum ferritin does not always reflect iron overload…A combination of both parameters expressed as ferritin/aspartate transaminase ratio was highly predictive of tissue iron overload…without exposing the patient to unnecessary risks and costs.”

“In human studies, high levels of iron, measured as plasma iron, transferrin saturation and total iron binding capacity (TIBC), have been associated with an increase in overall cancer risk and an increase in the risk of dying from any type of cancer.”

Interaction between iron and the polyunsaturated fats (PUFAs) powerfully promotes inflammation, damages metabolic performance, and has been shown to be a cause of degenerative disease, including cancer, MS and alzheimer’s. It is also a significant factor interfering with liver health, preventing the liver from being able to properly carry out many important pro-metabolism and detoxification functions.

“Increased lipid peroxidation with age is well accepted as an index of age-related increases in oxidative stress…usually attributed to…the vulnerability of lipid molecules to oxidative reactions, due to their unstable double bondings…in the absence of iron, little lipid peroxidation is detected.”

“…results obtained…highlight the importance of the presence of heme iron together with the type of dietary oil, in the formation of secondary lipid oxidation products that are well known as oxidative stress biomarkers. The urinary excretion of DHN-MA and MDA strongly depended on the type of oil used in diets. This was expected since MDA comes from the peroxidation of PUFA…”

“Iron overload…in the MS brain can contribute to pathogenesis of Multiple Sclerosis and iron imbalance is associated with a pro-oxidative stress and a proinflammatory environment…this suggest that iron could be a target for MS therapy…”

“In MS lesions, oxidative stress appears to play a major pathogenic role…radical injury can be further amplified by transition metals such as iron…and iron toxicity has been suggested to participate in neurodegenerative diseases…”

Some of the symptoms which are commonly blamed on iron deficiency include fatigue, dizziness or lightheadedness, headache, tongue swelling and inflammation, irregular heartbeats, chest pain, weakness or shortness of breath, irritability, impaired immune function, restless leg syndrome, thinning hair, dry skin, brittle nails, cold extremities, brain fog, poor appetite, depression and anxiety, and of course anemia.

Symptoms such as these often elicit recommendations to increase iron intake with supplements or fortified food items containing excessive amounts of iron, often in the more reactive and dangerous reduced ferrous form.

Realistically, those symptoms mentioned (and many others) blamed on a lack of iron, are often the result of chronic exposure to stress, and the suppression of metabolic energy systems. This includes anemia, which is a common symptom of impaired thyroid function.

Newly diagnosed 60 overt primary hypothyroid patients and 180 euthyroid controls were evaluated for anemia…Anemia was observed in 45 patients with hypothyroidism.”

“In the deficiency of thyroid hormones, anemia frequently develops and may be normocytic, hypochromic-microcytic, or macrocytic…In our study, anemia frequency was 18% in the subclinical hypothyroid patients and 11% in the overt hypothyroid group.”

“…chronic disease anemia is the most common type of anemia in hypothyroid patients similarly with the literature. Suspicion of hypothyroidism should be considered in every case of anemia with uncertain etiology.”

Actual iron deficiency anemia (although possible), is unlikely and should be the last suspected cause. In fact, keeping iron stores low can be extremely beneficial for health. Serum ferritin levels have been shown to increase and decrease relative to thyroid function.

The liver plays an important role enabling the effective performance of thyroid energy systems, and the proper removal of excess estrogen from circulation. Excess iron accumulation in the liver interferes with this process, and high estrogen promotes iron absorption, thyroid dysfunction and degenerative disease.

“Iron has not received much attention in discussions of estrogen-induced carcinogenesis…In humans, elevated body iron storage has been shown to increase the risk of several cancers including breast cancer. A role of iron in hormone-associated cancer in humans offers attractive routes for cancer prevention by regulating metal ion metabolism and interfering with iron accumulation in tissues.”

The polyunsaturated fats (PUFAs) are increasingly released out of storage into the system when thyroid function is sub optimal, worsening the inflammatory effects of interactions between estrogen and iron, potentially creating a vicious circle of iron dysregulation which can be difficult to deal with and harmful.

Interactions between estrogen and PUFAs promote the kind of conditions which help to change ‘free’ iron into the far more toxic and reactive reduced ferrous form, making iron more dangerous and damaging.

A diet avoiding the PUFAs and minimizing excessive intake of high iron foods, is a rational approach to improving health and avoiding many kinds of degenerative disease.

A suppressed thyroid metabolism slows digestive function and adds further strain on the liver, and this allows for increasing amounts of bacterial toxins to enter the system, causing inflammatory issues. Bacterial endotoxin (LPS) promotes the absorption of iron from food, and excess iron has been shown to interact with these toxins and promote the disease causing effects of endotoxin.

“…we review the evidence that….bacteria are a crucial feature of AD, that their growth in vivo is normally limited by a lack of free iron, and that it is this iron dysregulation that is an important factor in their resuscitation…A consequence of this is that the growing cells can shed highly inflammatory components such as lipopolysaccharides (LPS).”

A small amount of beef or lambs liver once a week has more than enough iron content. Because most cases of anemia are not a genuine reflection of low storage of iron – often being diagnosed on the basis of hemoglobin or red blood cell levels – improving thyroid function (rather than increasing iron intake) is generally all that is required.

Low testosterone has also been shown to increase the risk of anemia, and this makes sense in the context of metabolic suppression, high estrogen relative to progesterone, and an inflammatory state, all of which can be connected to excess iron.

“The risk of anemia associated with a low testosterone level and anemia was similar in the whole study population and in participants with normal serum iron levels and no deficiencies of iron…”

Vitamin A, vitamin K and copper have been demonstrated to be effective for improving iron status or different measures of anemia, avoiding an unnecessary increase in iron intake.

Anemia can also be the result of chronic inflammation, and so it may not be surprising to discover that iron promotes the release of nitric oxide, a powerful promoter of inflammation and a substance which helps to increase levels of free iron. Reducing iron stores also limits the production of the inflammatory stress substance, serotonin.

Iron increases serotonin and nitric oxide, and serotonin promotes nitric oxide and estrogen, and all of these things interfere with energy system metabolism and increase the risk of chronic inflammation, thyroid dysfunction and iron dysregulation.

“We concluded that NO is one of the mediators of iron-induced toxicity in proximal tubule cells…”

“It is concluded that CIO [chronic iron overload] triggers liver oxidative stress at early times, with upregulation of iNOS expression…”

Elevated iron levels are a risk factor for postmenopausal osteoporosis (PMOP), and it is reasonably common for menopause, chronic inflammation and thyroid dysfunction to go together.

“…reducing the iron overload has been demonstrated to benefit bone cell metabolism in vitro and improve the bone in vivo by normalizing osteoclastic bone resorption and formation.”

It has been suggested that PMOP is made worse as a result of insufficient estrogen, however this is based largely on the popular belief that menopause is a low estrogen state. In reality, chronic stress, iron dysregulation, thyroid and liver dysfunction, inflammation, and excess estrogen relative to progesterone go hand in hand and promote each other.

Focusing mainly on pro-metabolic foods like milk, cheese, and gelatin to get sufficient protein, and including plenty of carbohydrate from sweet ripe fruits, fruit juice, honey and white sugar, is a good way to reduce iron intake, and an effective method for avoiding many of the thyroid related symptoms mentioned, including anemia, often misdiagnosed as iron deficiency.

Apart from reducing intake of iron, there are a number of generally safe and easy ways to either lower iron stores, or protect against some of the dangerous effects of iron in the body. These include regular use of aspirin, vitamin E, supplementation with glycine and taurine, certain kinds of antibiotics as well as occasional blood donation.

“…iron reduction by phlebotomy decreased cancer risk in the apparently normal population. These results warrant reconsideration of the role of iron in carcinogenesis and suggest that fine control of body iron stores would be a wise strategy for cancer prevention.”

“In conclusion, our results suggest that ASA [aspirin] may chelate endogenous hepatic iron…”

“…results suggest that glycine could be a beneficial agent against iron mediated toxicity in hepatocytes.”

Many of the things which have been shown to protect against the toxicity of iron are also known to protect against the inflammatory and thyroid suppressive impact of the circulating PUFAs and excess estrogen (as well as numerous other stress related substances), and as such they can have powerfully synergistic disease protective, anti-aging effects.

Sugar lowers stress hormones and improves energy metabolism, limiting the release of the polyunsaturated free fatty acids and maintaining glycogen stores, helping keep blood sugar levels stable.

Sugar protects against inflammation and thyroid dysfunction, and as such can help to prevent anemia as well as iron dysregulation. Sugar powerfully suppresses cortisol which when high, can also be associated with an inflammatory anemic state.

Diabetes symptoms have been demonstrated to result from interactions between iron, PUFAs, stress substances (including serotonin, nitric oxide and estrogen) as well circulation of bacterial toxins.

“High-fat diets and iron overload are associated with insulin resistance, modified hepatic lipid and iron metabolism and increased mitochondrial dysfunction and oxidative stress.”

“…excess iron may diminish glucose utilization…and lead to a shift from glucose to fatty acid oxidation…”

“Iron-dextran administered…intraperitoneally resulted predominantly in iron uptake by the liver Kupffer cells and led to an increased NO level in blood in the presence of LPS [endotoxin].”

“Excess iron is usually stored in the liver, muscle, and pancreas and may cause organ-specific oxidative damage leading to insulin resistance and eventually beta-cell failure…higher iron stores may…contribute to the origin of type 2 diabetes in a generally healthy population.”

Sugar consumption (in the context of a nutritious diet low in iron and the difficult to digest starchy, fibrous, high PUFA foods) rather than being the cause of blood sugar dysregulation symptoms, is likely to be highly protective against them.

Too much iron can promote liver dysfunction, inflammation, estrogen excess, endotoxin issues, increased serotonin, nitric oxide and free fatty acid levels, and all of these things have not only been shown to promote diabetes, but inflammatory disease in general.

Regularly consuming coffee with the consumption of foods high in iron can possibly help to limit excessive absorption. As vitamin C may be able to increase the absorption of iron, it is probably a good idea to avoid drinking things like orange juice together with meat if you are attempting to lower iron stores.

Many of the positive effects attributed to iron supplementation, can be explained as the short term response of the body to the introduction of a stress promoting substance (for example causing an increase in red blood cells or hemoglobin). Some foods that supply iron, also provide generous amounts of pro-metabolic nutrients, and it is common for the credit for improvement to be incorrectly given to iron. Also harmful effects of iron can take significant time to show up, and are easily misattributed down the track to some other cause.

There are so many ways that too much iron in the system can damage proper thyroid metabolism, it seems ironic (or perhaps a little tragic) that suppressed thyroid function is the predominant cause of the symptoms which so often lead to a recommendation to supplement with iron.

How many of your health issues, rather than having anything to do with iron deficiency, are actually being caused by suppressed thyroid metabolism directly connected to excess iron and PUFAs stored in your body?

Read more here

Pathological mechanisms of hepatic tumour formation in rats exposed chronically to dietary hexachlorobenzene.

Ferritin levels in the cerebrospinal fluid predict Alzheimer’s disease outcomes and are regulated by APOE

Modulation of age-related alterations of iron, ferritin, and lipid peroxidation in rat serum

Gender difference in type 2 diabetes and the role of body iron stores

High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men.

Mitochondrial iron accumulation with age and functional consequences

Association Between Body Iron Stores and the Risk of Acute Myocardial Infarction in Men

Oxidative stress and inflammation in iron-overloaded patients with β-thalassaemia or sickle cell disease

Progressive iron accumulation across multiple sclerosis phenotypes revealed by sparse classification of deep gray matter.

Dietary and stored iron as predictors of breast cancer risk: A nested case–control study in Shanghai

Estimating iron overload in patients with suspected liver disease and elevated serum ferritin.

Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells.

Thyroid dysfunction in perimenopausal and postmenopausal women.

Effects of vitamin A supplementation on nutritional status of iron in healthy adults.

The Role of Iron in Diabetes and Its Complications

Iron induces hepatocytes death via MAPK activation and mitochondria-dependent apoptotic pathway: beneficial role of glycine.

The interplay between iron accumulation, mitochondrial dysfunction, and inflammation during the execution step of neurodegenerative disorders

Anemia frequency and etiology in primary hypothyroidism

T cell lipid peroxidation induces ferroptosis and prevents immunity to infection

Iron in Multiple Sclerosis and Its Noninvasive Imaging with Quantitative Susceptibility Mapping

Evidence suggesting that nitric oxide mediates iron-induced toxicity in cultured proximal tubule cells

Body Iron Stores in Relation to Risk of Type 2 Diabetes in Apparently Healthy Women

[Hypothyroidism associated to menopause symptoms worsening change with thyroid substitution therapy].

Iron-induced pro-oxidant and pro-lipogenic responses in relation to impaired synthesis and accretion of long-chain polyunsaturated fatty acids in rat hepatic and extrahepatic tissues.

Dietary polyunsaturated fatty acids and heme iron induce oxidative stress biomarkers and a cancer promoting environment in the colon of rats.

Aspirin intake and the use of serum ferritin as a measure of iron status.

Acute induction of anomalous and amyloidogenic blood clotting by molecular amplification of highly substoichiometric levels of bacterial lipopolysaccharide

Iron accumulation in multiple sclerosis: an early pathogenic event.

Effects of excess dietary iron and fat on glucose and lipid metabolism.

Taurine supplementation reduces oxidative stress and protects the liver in an iron-overload murine model

17β-Estradiol Inhibits Iron Hormone Hepcidin Through an Estrogen Responsive Element Half-Site

Mitochondrial iron chelation ameliorates cigarette-smoke induced bronchitis and emphysema in mice

Relation of iron stores to oxidative stress in type 2 diabetes

Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis

Iron dependence of tryptophan hydroxylase activity in RBL2H3 cells and its manipulation by chelators.

A novel endotoxin-induced pathway: upregulation of heme oxygenase 1, accumulation of free iron, and free iron-mediated mitochondrial dysfunction.

Iron and neurodegeneration in the multiple sclerosis brain

Iron chelation by cranberry juice and its impact on Escherichia coli growth.

Study of anemia in primary hypothyroidism

Iron Potentiates Acetaminophen-Induced Oxidative Stress and Mitochondrial Dysfunction in Cultured Mouse Hepatocytes

Iron metabolism, free radicals, and oxidative injury.

A Bacterial Component to Alzheimer’s-Type Dementia Seen via a Systems Biology Approach that Links Iron Dysregulation and Inflammagen Shedding to Disease

Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation

Iron, free radicals and cancer.

Role of iron in estrogen-induced cancer.

Iron and Neurodegeneration in Multiple Sclerosis

The endocrinology of perimenopause: Need for a paradigm shift

Iron chelation as a possible mechanism for aspirin-induced malondialdehyde production by mouse liver microsomes and mitochondria.

Pathogenic implications of iron accumulation in multiple sclerosis

Low Testosterone Levels and the Risk of Anemia in Older Men and Women

Involvement of splenic iron accumulation in the development of nonalcoholic steatohepatitis in Tsumura Suzuki Obese Diabetes mice

Aspirin intake and the use of serum ferritin as a measure of iron status.

Most free-radical injury is iron-related: it is promoted by iron, hemin, holoferritin and vitamin C, and inhibited by desferoxamine and apoferritin.

Reducing iron accumulation: A potential approach for the prevention and treatment of postmenopausal osteoporosis

Iron-Chelating Activity of Tetracyclines and Its Impact on the Susceptibility of Actinobacillus actinomycetemcomitansto These Antibiotics

Serum iron concentration is associated with subcortical deep gray matter iron levels in multiple sclerosis patients.

Bacterial endotoxin (lipopolysaccharide) stimulates the rate of iron oxidation.

Iron and Diabetes Risk

The Role of the Multiple Hormonal Dysregulation in the Onset of “Anemia of Aging”: Focus on Testosterone, IGF-1, and Thyroid Hormones

Dietary iron intake, body iron stores, and the risk of type 2 diabetes: a systematic review and meta-analysis

Body iron stores and risk of type 2 diabetes: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study

An update on iron chelation therapy

A study of anemia in primary hypothyroidism

Pathogenic implications of distinct patterns of iron and zinc in chronic MS lesions.

A novel method for assessing the role of iron and its functional chelation in fibrin fibril formation: the use of scanning electron microscopy.

Endotoxin increases hepatic susceptibility to lipid peroxidation: a possible role of iron.

Insulin resistance, atherogenicity, and iron metabolism in multiple sclerosis with and without depression: Associations with inflammatory and oxidative stress biomarkers and uric acid.

Body iron metabolism and pathophysiology of iron overload

Iron Accumulation with Age, Oxidative Stress and Functional Decline

The role of iron dysregulation in the pathogenesis of multiple sclerosis: an Egyptian study.

Iron Is a Sensitive Biomarker for Inflammation in Multiple Sclerosis Lesions

Anemia in male patients with cushing’s syndrome before and after cure

Sucrose intake and corticosterone interact with cold to modulate ingestive behaviour, energy balance, autonomic outflow and neuroendocrine responses during chronic stress.

Effects of iron deficiency on serotonin uptake in vitro by rat brain synaptic vesicles.

Nitric oxide and iron: effect of iron overload on nitric oxide production in endotoxemia.

Iron overload results in hepatic oxidative stress, immune cell activation, and hepatocellular ballooning injury, leading to nonalcoholic steatohepatitis in genetically obese mice

Chronic iron overload enhances inducible nitric oxide synthase expression in rat liver.

Serum ferritin as a marker of thyroid hormone action on peripheral tissues.

Iron supplements: the quick fix with long-term consequences

Characteristics of anemia in subclinical and overt hypothyroid patients.

Role of iron in carcinogenesis: cancer as a ferrotoxic disease.

Cerebral quantitative susceptibility mapping predicts amyloid-β-related cognitive decline.

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