Antioxidant use in IDH1 mutant tumors

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.:

https://www.ncbi.nlm.nih.gov/pubmed/24362902

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

metabolic therapies

Hello all,

I'm wondering if anyone has tried the Care Oncology Clinic protocol? They are now in the U.S. and I'm considering it as an additional therapy for my husband. I'm interested in hearing about potential side effects of the drugs, what neuro-oncologists had to say about it, etc. Also, he's currently on a hydroxicytrate/ALA combo and I'm wondering which metabolic treatment would be best/has better data. He's also doing a combination of TMZ/CCNU.

Another question-- his most recent MRI shows radiation necrosis. Is there data that shows any natural treatments that could help?

Thank you all!

Thoughts on ALA and Hydroxycitrate

Hi all,
I haven't posted before and am fairly new to the blog. I've been visiting it frequently over the past few weeks and I really appreciate all of the shared knowledge, opinions and helpful advice that I see here.

I am wondering if anyone has tried the alpha-lipoic acid/hydroxycitrate combination in addition to CCNU. My husband is 31 and is about to begin his second round of chemo, this time trying CCNU. He was diagnosed last April and went through the standard TMZ/radiation but had a recurrence in January. He had his second surgery in February and they were able to do a complete resection this time.

I've been reading a lot about alpha-lipoic acid and hydroxycitrate, also in combination with naltrexone, and I think it's something we want to try. I'm wondering if there are certain supplements or medications he shouldn't take at the same time... also curious what the recommended doses would be. Some of the studies I've read show that the ala was administered via IV which I don't think will be possible for us, especially because I expect his oncologist to be really hesitant about this treatment plan.

Also, is it possible to combine this type of treatment with CCNU and another drug like tamoxifen or Keytruda? So many options and I'm not sure which is the best to make a case for to his doctor.

He takes a number of supplements, including turmeric, garlic, goldenseal, resveratrol, boswellia, and vitamin D. He's also on metformin, a dose of 500mg twice a day. He's been on the ketogenic diet for almost a year.

I appreciate any insight.
Thanks!

Abby

*Edit: I should also mention that we are still waiting on the more extensive genetic testing results. His first pathology last year showed MGMT methylation-positive, IDH1 positive. ip19q negative.

Improvement of the ketogenic diet

In many studies, it has been shown that a ketogenic diet can be a useful supplement in the treatment of glioblastoma. I would like to discuss the improvement of this diet on the basis of recent research.

1. Ketogenic diet + α-lipoic acid and hydroxycitrate
2017 https://www.ncbi.nlm.nih.gov/pubmed/28122260
"To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models."

2016 http://crescopublications.org/pdf/CROOA/CROOA-2-019.pdf
"Combination of Metabolic Treatment of Aggressive Primary Brain Tumour
and Multiple Metastases of the Brain"
"We report the cases of 12 patients with advanced brain tumor. They were all treated with
conventional treatment and a combination of sodium R lipoate (800 mgbid), hydroxycitrate at 500 mg tid and low-dose naltrexone at 5 mg at bedtime. Eight patients had primary brain tumour (n=8 including five glioblastomas) four patients had multiple brain metastases."

2. Ketogenic diet + Fenofibrate ?
2016 https://www.ncbi.nlm.nih.gov/pubmed/26869992
"Our results reveal a new, intriguing aspect of cancer cell biology and highlight the benefits of fenofibrate as a supplement to both canonical and dietary (ketogenic) therapeutic approaches against glioblastoma."
2015 https://www.ncbi.nlm.nih.gov/pubmed/26172294
"Given that fenofibrate is a widely used non-toxic drug, we suggest its use in patients with glioblastoma multiforme (GBM)."
2017 https://www.ncbi.nlm.nih.gov/pubmed/28459367
"...the lipid-lowering agent fenofibrate...have potential to lower synthesis or effects of G(M)-CSF and thus deprive a glioblastoma of some of the growth promoting contributions of bone marrow and G(M)-CSF.
It's strange, but in this blog I did not find any information about Fenofibrate. So is it necessary to add it to the ketogenic diet?

3. Ketogenic diet + Inhibition of glutamine metabolism ?
2017 https://www.ncbi.nlm.nih.gov/pubmed/28720668
"Inhibition of glutamine metabolism slows the in vitro and in vivo growth of GLNHigh GBM cultures despite metabolic adaptation to nutrient availability, in particular by increasing pyruvate shuttling into mitochondria."
"...the pleiotropic metabolic inhibitor EGCG, targeting glutamine metabolism, specifically reduces tumor proliferation, in vitro and in vivo, of mesenchymal GLNHigh cells."
How can the findings of this study be used? Only EGCG can not inhibit glutamine metabolism. Maybe there are more options?

4. Ketogenic diet + Specialized medium-chain triglycerides (MCT) ?
2016 http://clincancerres.aacrjournals.org/content/22/10/2482
"MCTs were specifically chosen based on carbon chain lengths (C8:C10::97%:3%), which allow them to rapidly diffuse from the gastrointestinal tract into the hepatic portal system and travel directly to the liver where they are converted into ketone bodies."

5. What other ideas can you offer to enhance the effect of a ketogenic diet?

Alpha lipoic acid

I find this very interesting reading
http://jeffreydachmd.com/2016/05/alpha-lipoic-acid-anticancer-agent-burt-berkson-md/

Thoughts?