You guys produce excellent reviews. I love reading your magazine. Prior to reading one of your past issues I was taken in by the DIM hype, now I know I3C is the key.
Thanks for the recognition. AOR strives to keep on top of the research, and to base our formulations on the best available science -- not the hype.
If anyone is interested, the article with references comparing I3C with DIM as supplements to which lynx refers is now available online.
Could you explain something about how sulforaphane works, I read that it induces oxidative stress and thus increases Nrf2 expression. Any help would be appreciated.
I'm not intimately familiar with this, but is clear that part of the phase II detoxification process induced by sulforaphane is the result of sulforaphane somehow inducing Nrf2, resulting in an upregulation of the antioxidant response element (ARE), which then upregulates the transcription of various cytoprotective genes. Because this can happen in response to oxidative stress, it seems possible that sulforaphane is at least partly acating by increasing oxidative stress slightly, leading to a compensatory overactivation of cytoprotective defenses and a net protective effect on the cell -- ie, a classic hormetic response.
However, there is evidence that sulforaphane acts at the posttranscriptional level, perhaps through direct interaction with Nrf2 protein:
Of particular interest is that this posttranscriptional response is not unique ... because similar effects were observed in cells treated with ... four structurally diverse inducers of the ARE-dependent gene expression [including sulforaphane]. These observations provide evidence of a regulatory mechanism that increases the stability of Nrf2, resulting in its accumulation in the cell. This notion is confirmed by experimental results showing that the half-life of Nrf2 is extended in cells exposed to the same inducers. Because cycloheximide was used to block de novo protein synthesis in these experiments, these data provide evidence that a posttranslational mechanism is involved in increasing the Nrf2 protein level. [1]
Someone else might be more familiar with the latest studies on the molecular mechanism. However, the important things to know are that (a) the downstream mechanism is the induction of phase II detoxification enzymes including but not limited to the ARE, and that (b) in all reasonable models that I have seen sulforaphane from diet or supplements increases net cytoprotection against a range of insults and reduces net cancer risk from various insults -- a finding consistent with extensive epidemiology on the reduced risk of various cancers from consumers of sulforaphane-rich Brassica vegetables.
Hope that helps. To your health!
AOR
1: Nguyen T, Yang CS, Pickett CB. The pathways and molecular mechanisms regulating Nrf2 activation in response to chemical stress. Free Radic Biol Med. 2004 Aug 15;37(4):433-41.
