Putative Cancer Chemopreventive Agents of Dietary Origin—How Safe Are They?

Abstract

As cancer chemopreventive agents are intended for use by healthy individuals as prophylactics to prevent or retard the development of cancer, they must be amenable to ingestion over prolonged periods without toxicity. Therefore, putative chemopreventive agents need to undergo stringent testing to ensure their safety with regard to chronic exposure in humans. The diet is thought to be a source of chemopreventive agents, and dietary compounds are generally considered to be of low hazard, albeit this notion has not often been put to the test. Here the safety information available for 5 dietary putative chemopreventive compounds, indole-3-carbinol (I3C), curcumin, quercetin, epigallocatechin gallate (EGCG), and capsaicin is reviewed. For these agents, normal dietary intake, doses used in clinical trials, efficacious doses in rodents, and where available, toxic doses are compared. For curcumin, quercetin and capsaicin, toxicological data is only available from studies in rodents. Information on long-term effects in animals beyond 28 or 90 days is lacking for EGCG. Capsaicin and quercetin are suspected carcinogens. I3C and quercetin can modulate the absorption of other drugs given concomitantly. Without further investigation of their toxicology, it is difficult to recommend any of these agents for long-term use in the healthy population.

The dark side of curcumin

“…21 Accumulating data have demonstrated since then that curcumin can induce DNA damage and chromosomal alterations both in vitro and in vivo at concentrations similar to those reported to exert beneficial effect. [22][23][24][25][26][27][28][29][30] For instance, curcumin concentrations of 2.5 and 5 lg mL À1 were shown to induce DNA damage to both the mitochondrial and nuclear genomes in cells. 28 These reports raise concern about curcumin safety, as the induction of DNA alterations is a common event in carcinogenesis.…”

Lack of chronic toxicity and carcinogenicity of dietary administrated catechin mixture in Wistar Hannover GALAS rats

“…There is vast amount of scientific literature which suggests that EGCG is responsible for the majority of the potential health benefits attributed to green tea consumption (Khan et al, 2008). Regarding chemopreventive mechanisms, inhibition of activation of specific receptor tyrosine kinases (RTKs) (Shimizu et al, 2008) and related signaling pathways (Verschoyle et al, 2007) or apoptosis induction (Khan et al, 2006(Khan et al, , 2010Yang et al, 2002) have been focuses of attention.…”

ESCO report: Advice on the EFSA guidance document for the safety assessment of botanicals and botanical preparations intended for use as food supplements, based on real case studies

“…stomach, pancreas or rectum), some studies established an association between tea exposure and lower tumour incidence, while other studies established an association between tea exposure and higher tumour incidence (Higdon and Frei, 2003;IARC, 1991). Given these unclear findings and the absence of a life-long animal experimental study, there are reservations based on the current level of knowledge about the long-term ingestion of high-dose green tea preparations for the prevention of disease (Verschoyle et al, 2007).…”

“…growth inhibition and apoptose induction in the case of tumour cell lines) (e.g. :, Higdon and Frei, 2003;Verschoyle et al, 2007;Lee et al, 2005;Muto et al, 2001, Paschka et al, 1998Chung et al, 1999;Aktas et al, 2004) but also of possible adverse effects such as the ones described hereafter (e.g. Lambert et al, 2007).…”