Extensive in vivo toxicity studies have been performed
with turmeric Oleoresin (85% curcumin) which led to it
being placed on the FDA's GRAS (generally recognized as
safe) list [54]. Kawanishiet al. (2005) remarked that
curcumin, like many antioxidants, can be a "double-edged
sword" where, in the test tube, anticancer and antioxidant
effects may be seen in addition to pro-oxidant effects [66].
Carcinogenic effects are inferred from interference with the
p53tumor suppressor pathway, an important factor in human
colon cancer [67]. Carcinogenic and LD50 tests in mice and
rats, however, have failed to establish a clear relationship
between tumorogenesis and administration of curcumin in
turmeric oleoresin at >98% concentrations [68]. Other in
vitro and in vivo studies suggest that curcumin may cause
carcinogenic effects under specific conditions [69,70].
Clinical studies in humans with high doses (2–12g) of
curcumin have shown few side effects, with some subjects
reporting mild nausea or diarrhea [71]. More recently,
curcumin was found to alter iron metabolism by chelating
iron and suppressing the protein hepcidin, potentially causing
iron deficiency in susceptible patients [72]. Further studies
seem to be necessary to establish the benefit/risk profile of
curcumin [73].