Novel insights into the interaction between iron and curcumin and its physiological consequences

Ferrous iron salts are used to prevent and treat iron deficiency and iron deficiency anaemia. However, supplemental iron absorption is limited leading to oxidative stress in the intestinal mucosa and gastrointestinal (GI) symptoms that eventually compromises patient adherence to treatment. Iron supplementation in endurance athletes may be even more challenging as intense endurance exercise upregulates hepcidin, the master regulator of iron homeostasis that restrains intestinal iron absorption and causes GI adverse events. Co-administration of ferrous iron with curcumin, a polyphenol from turmeric root, might ameliorate oral iron- and exercise-induced GI disturbances due to its potent antioxidant and anti-inflammatory activity. Therefore, this thesis aimed to explore the co-administration of supplemental iron with curcumin (native and formulated) with regards to (i) alleviation of iron and exercise-related GI perturbations and (ii) influence on iron absorption and hepcidin.

To attain these aims, mechanistic studies on an intestinal cell model (Caco-2 cell line) were conducted along with a clinical trial. Caco-2 cells were treated with multiple combinations of iron and native and formulated curcumin forms, including the commercially available HydroCurc®. Finally, a placebo-controlled, randomised, double blind, cross-over study was conducted to assess intestinal damage and distress and iron homeostasis in runners taking 65 mg ferrous iron and either HydroCurc® (500mg) or placebo for one week.

In a Caco-2 model of duodenal iron overload, HydroCurc® led to a greater Caco2 cell proliferation vs native curcumin (p<0.0001) and mitigated the iron-induced permeability of Caco-2 monolayers. Additionally, HydroCurc® increased cellular ferritin to up to 160.5% vs cells treated only with iron (p<0.0001). The formulated curcumin also demonstrated a 2.1-fold greater ferric iron reducing capacity than native curcumin (p=0.0003). Co-administration of iron and HydroCurc® for one week led to a 39.57% reduction in serum hepcidin (p=0.0457) and decreased post-exercise hepcidin response to 48.15% (p=0.0081). Ferritin, IL-6, IFABP and GI symptoms did not differ between groups.

This thesis provides novel findings on the interaction and effect of curcumin forms and iron on GI health and iron homeostasis. Caco-2 and human data indicated that HydroCurc® might improve supplemental iron absorption by maintaining the metal in its readily absorbable ferrous oxidation state and by downregulating both baseline and post-exercise hepcidin. Future research is warranted to clarify co-administration impact on ferritin as well as on hepcidin regulation pathways. Moreover, as the GI restorative role of curcumin forms was not fully explored in this thesis, more research on this aspect is required.