Iron excess treatable by copper supplementation in acquired aceruloplasminemia: a new form of secondary human iron overload?

Abstract

EGCG, by inhibiting both CYP3A4 and P-glicoprotein activities, increased the bioavailability of the calcium channel blockers verapamil and diltiazem, 8,9 thus raising the risk for patients to undergo atrioventricular block. The inhibition of CYP3A4 activity by green tea extracts could increase the plasma concentrations of midazolam 4 and, therefore, amplify the risk of prolonged sedation. On the contrary, the up-regulation of CYP1A2 could result in reduced bioavailability of the antipsychotic drug clozapine. 6 Furthermore, both green and black tea extracts inhibited the activity of the isoforms 1A1 and 1A3 of sulfotransferases, 10,11 a family of enzymes involved in the metabolism of drugs such as methyldopa or ␤2-adrenoceptor agonists, thus increasing their plasma concentrations and side effects. With regard to the plasma concentrations of EGCG in people drinking green tea, it is interesting to note that the values found by Chow and colleagues and quoted by Shah et al 2 could be underestimated. In fact, Chow et al measured plasma EGCG after a single administration of green tea to healthy volunteers. Considering that catechins are metabolized by sulfotransferases and the latter is inhibited by the former, 10,11 catechin plasma concentration could significantly increase in people consuming a large amount of green tea.Finally, the rationale for use of green tea as an adjuvant in cancer therapy has been contradicted by recent clinical studies that demonstrated the inconsistent effect of green tea in preventing the occurrence of esophageal, stomach, liver, colorectal, and breast cancers. 12,13 In our opinion, it is a matter of public health to refrain from providing people with confusing information about the unproven therapeutic potential of tea derivatives without consistent information on their toxicity.

Levels of plasma ceruloplasmin protein are markedly lower following dietary copper deficiency in rodents

“…However, older anemic P53 male CuD rats in the current study had liver Fe levels twice that of CuA controls consistent with a role for low Cp activity associated with anemia and tissue Fe retention. Humans with copper deficiency also have hepatic iron overload, anemia, low ferroxidase activity and low serum iron, supporting the current experimental models (Videt-Gibou et al, 2009). However, the Cp driven mechanism is not totally clear.…”

Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver

“…Moreover, high iron consumption has been reported to interfere with copper absorption in infants and adults (148). It has been further suggested that iron overload can perturb copper utilization (295, 296). For example, immunoreactive CP was reported to be decreased in hereditary hemochromatosis (HH), a genetic iron-loading disorder (67).…”

Iron, hepcidin, and the metal connection

“…However, whether zinc is associated with copper chelating therapy during the active or maintenance phase of treatment remains to be discussed (Schilsky, 2009). Recently, the impact of zinc on copper metabolism was reinforced by the description of a new form of systemic iron overload (Videt-Gibou et al, 2009) related to secondary aceruloplasminemia resulting from excessive zinc intake (Nations et al, 2008). The defect is corrected by copper supplementation.…”