I'd like to open a topic up for debate here regarding antioxidant use in IDH1 mutant tumors. My understanding is that IDH1 mutant tumors are characterized by generally low Glutathione (antioxidant) levels, significantly sensitizing them to ROS generation. Some researchers speculate that this is the primary reason for superior OS stats for IDH1 mutant tumors, e.g.:
Given this particular dynamic, should I conclude that use of antioxidants which stimulate Glutathione (e.g. Alpha Lipoic Acid, Green tea, Cinnamon,...) should better be avoided in the case of IDH1 mutant tumors?
I am particularly interested in this question as my tumor is IDH1 mutated, and I recently started taking the Metabloc protocol (Alpha Lipoic Acid + Hydroxycitrate), since it seems to deliver very promising synergy with Metformin use. After investigating a bit, I am contemplating skipping the Alpha Lipoic Acid, however.
Any thoughts on this topic? Thanks!
John
It really depends. All lot depends on how much the molecule is crossing the blood-brain barrier and accumulating in the tumor, and that is different for each type of molecule. This is a topic that is relatively understudied, so much of the discussion would have to be speculation versus actual evidence.
ReplyDeleteMy impression is that tumor cells have a generally higher level of oxidative stress than normal cells so actually have a higher need for antioxidants. But most antioxidants have multiple functions, some of which could be more important than their antioxidant function. Green tea extracts for example can synergize with chemo by inhibiting GRP78, which has nothing to do with it being an antioxidant.
https://www.ncbi.nlm.nih.gov/pubmed/21257259
Consequently I tend not to think in general terms of antioxidant/non-antioxidant, but instead believe you have to look at the evidence for each individual molecule separately, as every antioxidant is different, with different pharmacokinetic properties, and different additional functions beyond their antioxidant functions. When doctors say to "avoid antioxidants" during standard therapies, this is a simplistic view, but perhaps an understandable position to take given the complexity of the topic.
Thanks a lot, Stephen. I have generally opted to use antioxidants rather than avoid them, and so far it seems to have worked for me. I have opted to take the Alpha Lipoic Acid anyway, to give the Metabloc combination a chance. Lets see how it goes... I guess it is hard to avoid making risky choices in one way or another, given data scarcity and scientific knowledge gaps. So gut feeling becomes an important decision criteria in the end.
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