Hepcidin in blood stream, how to lower levels
June 8 2018

Hepcidin is a liver-derived hormone that degrades the ferroportin transport channel, thus reducing the ability of macrophages to recycle damaged iron, and decreasing iron availability.

Iron in the body and brain
Iron absorption is regulated by circulating hepcidin. Stored samples from a human iron absorption study were used to test the hypothesis that differences in plasma hepcidin explain interindividual variation in iron absorption. Hepcidin-25 concentrations were measured in fasting samples from men recruited to a study investigating the relation between the HFE genotype, iron absorption, and iron status. Log iron absorption was negatively correlated with serum ferritin and with plasma hepcidin but was unaffected by genotype. There was a positive correlation between hepcidin and ferritin. Plasma hepcidin in isolation significantly predicted 36% of the interindividual variation in iron absorption. Plasma hepcidin and serum ferritin concentrations are highly correlated, and, in the normal range of plasma hepcidin values, 36% of interindividual differences in iron absorption are explained by differences in circulating plasma hepcidin.

Trends Pharmacol Sci. 2014. The pathophysiology and pharmacology of hepcidin. Inappropriate production of the iron-regulatory hormone hepcidin contributes to the pathogenesis of common iron disorders. Absolute or relative deficiency of hepcidin causes iron overload in hereditary hemochromatosis and iron-loading anemias. Elevated hepcidin causes iron restriction in inflammatory conditions including autoimmune disease, critical illness, some cancers, and chronic kidney disease. Multiple agents targeting hepcidin and its regulators are under development as novel therapeutics for iron disorders.

J Transl Med. 2018. Hepcidin, an emerging and important player in brain iron homeostasis. There are two sources of hepcidin in the brain; one is local and the other comes from the circulation. Little is known about the molecular mediators of local hepcidin expression, but inflammation and iron-load have been shown to induce hepcidin expression in the brain.

Flaxseed
Hemodial Int. 2016. Effects of flaxseed oil on blood hepcidin and hematologic factors in hemodialysis patients. Tabibi H, Mirfatahi M. This study indicates that daily consumption of 6 g flaxseed oil reduces serum hepcidin and improves hematologic factors in hemodialysis patients.

Phytoestrogens
Free Radic Biol Med. 2015. Phytoestrogens modulate hepcidin expression by Nrf2: Implications for dietary control of iron absorption. Hepcidin is a liver-derived antimicrobial peptide that regulates iron absorption and is also an integral part of the acute phase response. In a previous report, we found evidence that this peptide could also be induced by toxic heavy metals and xenobiotics, thus broadening its teleological role as a defensin. The ability of phytoestrogens to modulate hepcidin expression in vivo suggests a novel mechanism by which diet may impact iron homeostasis. Polyphenolic small molecules or phytoestrogens commonly found in fruits and vegetables including the red wine constituent resveratrol can induce hepcidin expression in vitro and post-prandially, with concomitant reductions in circulating iron levels and transferrin saturation by one such polyphenol quercetin.

Q. Thank you for an awesome website with so much knowledge! If someone takes up too much iron due to HFE hereditary hemochromatosis, should they, or should they not, use phytoestrogens? Your article states that phytoestrogens modulates the production of hepcidin, but I dont understand if they stimulate or inhibit production.
   A. There is very little clinical research on this, but it appears that intake of phytoestrogens may induce hepcidin production which could be beneficial in those with HFE, but I cannot be 100 percent certain until actual studies are done in humans.