Curcuma decreases serum hepcidin levels in healthy volunteers: a placebo‐controlled, randomized, double‐blind, cross‐over study

Abstract

Hepcidin, secreted by hepatocytes, controls iron metabolism by limiting iron egress in plasma. Hepcidin is upregulated during inflammation through the activation of the signal transducer and activator of transcription 3 (STAT3) transduction pathway, which decreases iron bioavailability and may explain the anemia of chronic inflammatory disease. In vitro, it has been shown that curcumin can decrease hepcidin synthesis by decreasing STAT3 activity. We conducted a proof-of-concept study to assess the effect of curcuma on hepcidin synthesis in human. This was a placebo-controlled, randomized, double-blind, cross-over, two-period study performed in 18 healthy male volunteers. Subjects received a single oral dose of 6 g curcuma containing 2% of curcumin or placebo. Serum hepcidin and iron parameters were assessed repeatedly until 48 h after dosing. When compared with a placebo curcuma decreased hepcidin levels significantly at 6 h (-19%, P = 0.004), 8 h (-17%, P = 0.009), and 12 h (-17%, P = 0.007) and tended to decrease hepcidin at 24 h (-15%, P = 0.076). Curcuma also significantly increased serum ferritin levels at 6 and 8 h (+7% for both times, P = 0.018, 0.030, respectively) and had no effects on serum iron, transferrin, and transferrin saturation. This pilot study showed that curcuma decreases serum hepcidin levels in human and supports the idea that curcuma could be useful in treating hepcidin overproduction during inflammatory processes. Confirmatory studies in patients with chronic inflammation are now required to determine the optimal dose and therapeutic scheme of curcuma.

Curcumin induces mild anemia in a DSS-induced colitis mouse model maintained on an iron-sufficient diet

“…Our results are in agreement with previous work reporting that curcumin supplementation decreases hepcidin levels both in mice (9) and humans (29). This regulation has been associated with the inhibition of phosphorylation of the signal transducer and activator of transcription 3 (STAT3) (16,29) and TNF activation (48). MyD88 has also been implicated as an important factor for hepcidin regulation as MyD88-deficient mice are unable to appropriately upregulate hepcidin expression when iron-challenged and develop iron-loading in the liver (31).…”

Hepcidin Therapeutics

“…STAT3 inhibitors, such as curcumin, AG490 or PpYLKTK were reported to inhibit inflammatory induction of hepcidin in cultured cells [131], and in case of AG490 also in mice [132]. Moreover, a single oral dose of curcuma containing 2% curcumin decreased hepcidin in healthy volunteers; however, this had no effect on serum iron [133]. Acetylsalicylic acid (aspirin) was shown to downregulate hepcidin by decreasing JAK2 and STAT3 phosphorylation in murine BV-2 microglia [134] and rat PC12 pheochromocytoma cells [135], but the relevance of this finding to hepatocellular hepcidin is unknown.…”

Iron Metabolism in Prostate Cancer; From Basic Science to New Therapeutic Strategies

“…This is probably the reason why TFR1 blockade in addition to curcumin supplementation improves the suppressive effect of this compound in PCa ( 116 ). It could be that the additional effect of curcumin in PCa is mediated by its inhibitory effect on hepcidin expression, which has already been observed in hepatocytes, but it has not been studied in PCa ( 117 – 119 ). Other compounds with iron chelating properties have been used in PCa cultured cells, such as epigallocatechin gallate (EGCG) ( 120 ).…”