The term hemochromatosis describes a condition of excess iron in the body, and primary hemochromatosis (also known as hereditary hemochromatosis) and secondary hemochromatosis stand as the two main forms. A buildup of iron can be quite toxic and frequently damages such organs as the heart, liver, and pancreas (as well as joint tissues) [1].
Secondary or acquired hemochromatosis commonly manifests as a result of frequent blood transfusions, very high dietary or supplemental iron intake, significant hemolysis or the rupturing of red blood cells (can be due to microbial infection, autoimmunity, genetic disorders, etc.), too much alcohol consumption, or some kind of liver disease (like chronic viral hepatitis) [2] [3]. Signs and symptoms of hemochromatosis may include: abdominal pain, hair loss, fatigue, joint pain, weight loss, bronzing or darkening of skin color, and low libido [4]. The diagnosis of hemochromatosis may involve one or more of the following blood tests: serum iron, serum ferritin (iron storage protein), transferrin saturation (transferrin is an iron transport protein), and total iron-binding capacity (an indirect transferrin measure) [5]. An MRI, liver biopsy, or genetic test may also be employed to confirm or assess clinical findings [6]. The human body doesn’t really have a mechanism for excreting extra iron, so iron accumulation is largely a matter of intestinal absorption and release from macrophages. Phlebotomy or blood draws weekly or periodically is the chief method of treatment for iron overload issues, though pharmaceutical iron chelators like deferoxamine, deferasirox, and deferiprone are also available [7]. Erythrocytapheresis or the removing of red blood cells from whole blood extracted from the patient is another option. Hereditary hemochromatosis is often characterized by a mutation in the HFE gene promoting undue intestinal iron absorption, but mutations in other genes associated with iron metabolism (like HJV, HAMP, TFR2, and SLC40A1) can lead to forms of iron overload very similar to classical hereditary hemochromatosis, and since iron overload can arise in the absence of a strong genetic contributor, hemochromatosis can be more accurately viewed as an umbrella under which multiple conditions with similar clinical features exist [8] [9] [10]. And it’s important to understand, as Dr. Ernest Beutler has explained, that the simple presence of the hereditary or HFE hemochromatosis genotype is insufficient for the development of clinical disease [11]. Dr. Beutler agreed with the 1955 contention of Finch and Finch that the “hemochromatosis mutation” is common, but the hemochromatosis disease is rare or at least uncommon [12]. Fun fact: Ernest earned his doctorate degree in medicine from the University of Chicago at the age of 21. It would also be more correct to classify hemochromatosis as a disorder of iron metabolism (usually involving dysregulation of the hepcidin-ferroportin axis), rather than just iron abundance [13]. The pathophysiology for hemochromatosis conditions is complex, so let’s just focus on some highlights pertinent to this article. Firstly, hepcidin, encoded by the HAMP gene, is a major regulator of systemic iron homeostasis. Hepcidin is an antimicrobial peptide predominantly made by hepatocytes (liver cells) whose production is stimulated by inflammation, iron loading, and cellular signals from endoplasmic reticulum stress (endoplasmic reticula are organelles present in almost all cells of the body) [14] [15]. A rise in hepcidin normally coincides with a fall in serum iron due to lower iron absorption from the gut and higher iron trapping by macrophages. Hepcidin expression is inhibited by anemia (low hemoglobin or red blood cells), hypoxia (low tissue oxygen), and increased erythropoietic activity (the making of red blood cells in red bone marrow) [16]. So hepcidin levels go up with inflammation or microbial infection, and go down with anemia or hypoxia. Therefore, improving oxygenation (with a supplement like Germanium-132 for example) could be used to treat high iron levels. Coming back to the fact that endoplasmic reticulum stress triggers hepcidin release, since endoplasmic reticula perform the heavy lifting of cellular-level detoxification, the deficiency of hepcidin commonly seen in hemochromatosis may reflect an exhaustion of hepcidin expression from overstimulation due to toxicity and dysbiosis (bacterial lipopolysaccharide can induce hepcidin production in macrophages for example) [17] [18]. Accordingly, understanding the presentation of hemochromatosis as being reflective of a weak or overwhelmed liver coupled with adrenal stress, we can prioritize detoxification and adrenal support in the treatment program. Next, we know that the body can withhold iron from potential pathogens as a defense strategy for thwarting infection. This withholding is achieved by reducing the amount of iron bound to serum transferrin [19]. And the body can choose to absorb less iron from the gut during times of inflammation to deprive pathogens of iron. But with chronic inflammation and stress, I contend that the body’s iron withholding mechanism could become dysregulated or fatigued. Because iron overload can compromise the ability of phagocytes (like macrophages and neutrophils) to engulf and destroy pathogens, and because the virulence of many microorganisms can be enhanced by an abundance of iron, it’s hard to argue against microbial infection or dysbiosis being able to both promote the onset and fuel the maintenance of hemochromatosis [20]. So resolving microbial infections or dysbiosis may be very necessary in the treatment of chronic states of iron overload. Some of the microbial and viral genera containing species whose growth or virulence rises in response to iron availability include: Candida, Cryptococcus, Entamoeba, Plasmodium, Toxoplasma, Clostridium, Mycobacterium, Staphylococcus, Streptococcus, Escherichia, Klebsiella, Pseudomonas, Salmonella, Cytomegalovirus, Parvovirus, Hepatitis B virus, and Hepatitis C virus [21]. And I think it’s worth mentioning that Human cytomegalovirus protein US2 can downregulate the HFE gene’s expression (which fosters high serum iron), possibly encouraging the persistence or proliferation of viruses in general [22]. Also, remember that alcohol consumption is related to hemochromatosis. Yeast organisms like Candida albicans can ferment ingested sugar into ethanol, which can then be metabolized into acetaldehyde. Acetaldehyde is toxic and can hinder the function of white blood cells, as well as contribute to anemia by rigidifying the cell membranes of red blood cells [23]. So consider Candida overgrowth as a possible factor in the pathogenesis of iron overload. To quickly summarize, so far we’ve identified inflammation, dysbiosis, toxicity, and hypoxia as ingredients in the brewing of hemochromatosis. Now let’s look deeper into iron metabolism and homeostasis. Again, hepcidin plays a dominant role in iron trafficking, and an abnormally low presence of hepcidin yields a large uptake of iron from the gut and a large release of iron from storage sites, leading to tissue iron saturation [24]. Now, the liver stands at the central axis of iron metabolism, for it is the main site of ferritin (iron storage protein) and transferrin (iron transport protein) synthesis, and it is where HFE protein, transferrin receptor 2, and ferroportin are preferentially expressed. HFE protein modulates hepcidin and transferrin-mediated iron uptake, transferrin receptor 2 helps with the cellular uptake of transferrin-bound iron, and ferroportin exports iron or pushes it out of cells [25] [26] [27]. Iron is recycled by macrophages which break down senescent red blood cells and hand over the scavenged iron to transferrin for transport throughout the body and to red bone marrow so that it can be incorporated into hemoglobin. Summarizing again, there is a triad between the liver, the gut, and the immune system that is responsible for iron sensing, iron uptake, and iron release, and thus the systemic distribution and utilization of iron [28]. Ergo, in crafting a plan for the remedying of hemochromatosis, we should look to the liver, the gut, and the immune system and identify hindrances, weaknesses, and flaws in these components of the body. Moving on to some natural treatment options, let’s first pay heed to the following recommendations typically given to hemochromatosis patients [29]: - Obviously avoid iron supplementation. - Consume red meat in moderation. - Limit or abstain from alcohol consumption. - Limit supplemental vitamin C to 500 mg daily or take supplemental vitamin C away from meals. - Avoid raw shellfish. Now we can cover some recommendations and supplement options: - Intestinal iron absorption can be enhanced by vitamin C but diminished by calcium, zinc, and manganese, so many leafy greens are great for those with hemochromatosis [30] [31]. - Vitamin D seems to play a part in the hepcidin-ferroportin axis, and so getting some sun or supplementing with a reasonable dosage could be helpful [32]. - Alpha-lipoic acid is a potent antioxidant and anti-inflammatory, and because it can chelate and help remove excess iron, its use is indicated in hemochromatosis (note that alpha-lipoic acid can also chelate copper) [33]. - Low vitamin E levels have been seen in hemochromatosis patients, and since such patients need to be careful with their intake of vitamin C, vitamin E makes a great alternative antioxidant [34]. - Because S-adenosylmethionine (SAMe) can be low in those with liver disease due to a hampered conversion of methionine to SAMe, SAMe supplementation could up the body’s methyl donor supply and help knock down inflammation [35]. S-adenosylmethionine has been used to improve liver function in an animal with hemochromatosis, but it’s hard to say how much benefit was derived from the SAMe as deferoxamine and phlebotomy were also employed [36]. - N-acetylcysteine is another excellent antioxidant (NAC is a glutathione precursor) and anti-inflammatory, and has demonstrated liver protection in a murine model of alcohol-induced liver damage [37]. More importantly, NAC can bind to redox-active metals like iron (and copper) and therefore may improve iron overload (though a relatively high dose may be needed) [38]. - Curcumin is a well-known antioxidant and iron chelator and has been found to be very beneficial for those with iron overload or liver damage [39]. Specifically, curcumin decreased serum iron, spleen iron content, and liver iron content in mice [40]. - Intestinal sanitation can be imperative in the correction of iron overload and conditions of liver stress. Germane to liver status, probiotics can improve gut barrier health, modulate innate and adaptive immune function, and reduce the concentration of harmful gut microbes (note that the liver receives about 70% of its blood supply from the gut via the hepatic portal vein) [41]. Probiotics have demonstrated particular usefulness in the treatment of liver diseases [42] [43]. - It wouldn’t hurt to filter your drinking water to reduce iron intake from this source [44]. - As a supplement, pectin may be able to bind iron and partially block its absorption [45]. - Similar to curcumin, EGCG (epigallocatechin gallate) from green tea is an antioxidant and iron chelator, and can inhibit iron absorption from the gut, as can grape seed extract [46]. - The polyphenols quercetin, chrysin, rutin, and myricetin are all capable of chelating iron, and both quercetin and myricetin have rivaled the drug deferoxamine in vitro [47] [48] [49]. In a mouse model, quercetin and baicalin (another polyphenol) were shown to decrease liver iron content as well as iron-induced lipid peroxidation and protein oxidation in the liver, in addition to increasing iron excretion via stool [50]. - Milk thistle is commonly recommended for hemochromatosis and liver issues in general, and its flavonolignan complex silymarin can serve as a strong antioxidant, anti-inflammatory, antifibrotic, and regenerant tonic for the liver [51]. Silymarin can chelate iron, reduce iron absorption, and drop serum ferritin [52] [53] [54]. - Inositol hexaphosphate (IP6) or phytic acid possesses a familiar capacity to bind iron in the gut, but it can also protect the liver against free radical damage and lower both serum iron and serum ferritin [55]. Inositol hexaphosphate can be taken with food to blunt iron absorption, but it would be more effective for hemochromatosis when taken in-between meals so that it can readily enter the bloodstream. In conclusion, we know what can promote the manifestation of hemochromatosis and we know what can be done to address and even resolve those factors. Hemochromatosis patients need not be stricken of hope by incorrect and outdated understandings of conventional medicine. Hopefully this article was of some avail to you. References:
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AuthorDenton Coleman is an Exercise Physiologist and Medical Researcher. Archives
October 2023
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