CBD + ALA combination (GBM)

Hi

Do you have any thoughts on combining CBD with alpha-lipoic acid (ALA)? I haven't found any specific research on a combination. I am particularly interested in IDH-wild



Also... I would like to link some interesting stuff :

Concomitant Treatment of Malignant Brain Tumours With CBD - A Case Series and Review of the Literature
https://pubmed.ncbi.nlm.nih.gov/31570484/
"a total of nine consecutive patients with brain tumours are described as case series; all patients received CBD in a daily dose of 400 mg concomitantly to the standard therapeutic procedure of maximal resection followed by radiochemotherapy. By the time of the submission of this article, all but one patient are still alive with a mean survival time of 22.3 months (range=7-47 months)".

Inhibition of autophagic flux differently modulates cannabidiol-induced death in 2D and 3D glioblastoma cell cultures
https://www.nature.com/articles/s41598-020-59468-4
(CBD + chloroquine + radiation)

RelA-activity is essential for Cannabidiol-mediated cytotoxicity
https://academic.oup.com/neuro-oncology/article-abstract/21/Supplement_6/vi70/5619524?redirectedFrom=fulltext (no full research report available)
"We observed therapeutic efficiency of CBD in a subset of GBM, obtained genetic markers indicating CBD-sensitive GBM and found that the p53 status segregated cell-death modes".

Additionally - if somebody is considering CBD, CBG, or FECO, there is a new report you might be interested in (sadly, no real specifics, that's commercial research):
https://thegreenfund.com/mcg-pharma-cannabinoid-formula-to-treat-glioblastoma

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

Alpha lipoic acid and hypoxia

Some patients use alpha lipoic acid in the treatment of glioblastoma. For example, it is part of the Metablock protocol or is accepted to minimize side effects of DCA.

However, this new study contains strange conclusions:

Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line.

https://www.ncbi.nlm.nih.gov/pubmed/30590317
https://www.sciencedirect.com/science/article/pii/S0753332218355070?via%3Dihub

"More importantly, we found ALA reduced the percentage of apoptotic cells and increased the MTT levels in the cells.
...inhibition of TRPA1-mediated Ca2+ entry through ALA treatment may not be a potential strategy for killing the glioblastoma cancer cells"

As you know, the tumor is very often hypoxic due to the use of Avastin.

Does this mean that alpha-lipoic acid should be avoided if there is a suspicion that the tumor has become hypoxic?

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!

Semyon's mom's profile.

My mother had an operation (in Germany, Frankfurt am Main) - removal of the tumor by 99%, and then - the rapid growth of the tumor to its former size (for 3 weeks)! The doctors were in shock.
(Glioblastoma, MGMT methylated)
10 days after chemoradiotherapy, MRI still showed tumor growth. The doctors decided that TMZ did not work in our case and suggested urgently switching to Avastin and Irinotecan.

Thinking, we decided to use a low dose of Avastin + CCNU.
I also decided to add 5 days of low TMZ after every day of CCNU.

The OncoDeep report showed the likely effect of Sirolimus, Olaparib and Trametinib.
I flew to Delhi (India) and bought at low price LYNPARZA Olaparib (1 bottle of 112 capsules of 50 mg) and MEKINIST Trametinib (1 bottle of 30 2 mg tablets).

Unfortunately, it is very difficult to interpret MRI. 3 doctors who watch my mom's MRI say sometimes the opposite conclusion!

Comments:

1. Suppression of T4 is very slow. We spent 3.5 months to reduce T4 from 12.4 to 3.3pmol / l. Also, T3 has fallen dramatically, although we take synthetic T3. Because of this, drowsiness and lack of appetite.

When suppressing T4, you can not take selenium, since it increases the production of the hormone T4! We started taking selenium and the hormone T4 took off from 3.3 to 5.14! Now with great difficulty again we need to knock it down((

2. For all treatment, my mother lost a lot of weight. From 65 kg (in January) to 52 kg (now). However, I do not see anything that we could refuse.

3. We bought a special meter and ketone strips to check that the mother is ketosis.

4. I ordered Mebendazole chewable tablets from Thailand for 500 mg / tablet. Maybe we will try to take large doses: 2-3 grams per day.

5. We use a higher dose of perillyl alcohol than Dr. Dr. Clóvis Orlando: 30 drops instead of 21. No unpleasant sensations! We plan to increase the dose to 40 drops. Dr. Clóvis Orlando wrote that they use perillic alcohol of 96% from Sigma Aldrich and that the other perillyl alcohol will not have an effect on GBM.

MRI-1: https://drive.google.com/open?id=1tPKrQgjIZzBgefhkknxNlQKbaC04XMI_

MRI-2: https://drive.google.com/open?id=1t3SgxGgJFi19i9qIwc47JucsV6ZCbLFa

MRI-3: https://drive.google.com/open?id=1JbRYk3DCUK87ndeRQK-Q7V7130oObiMV

MRI-4: https://drive.google.com/open?id=1Q6WFd9qtFAd18czkd5ouKYloIVBKuFS1

MRI-5: https://drive.google.com/open?id=1L-O1BgoVMohI7eXxH35qN__rNBDy3hrM

MRI-6: https://drive.google.com/open?id=1xWYd5_UsrAYb-c4wv49DSWTeJEN8Dl_F

MRI-7: https://drive.google.com/open?id=1MCpzZxPnl7eI1iigzJVWrOo2o4s8hKWz

MRI-8: https://drive.google.com/open?id=1De95kb-iZ30X7scIbZkeXxFq4KV5fgdT

11C-methionine PET 17.05.2018:
https://drive.google.com/open?id=18AaVybu5nvBH_cAe5QIfzO-efiwsUfkc

OncoDEEP report: https://drive.google.com/open?id=1A3dophOME6gY1GNdOHWE48wVYJUu_nHc
http://btcocktails.blogspot.ru/2018/02/our-report-oncodeep-what-do-you.html

 

The combination of DCA and a high dose of R-lipoic acid.

The MetaBloc protocol, which includes 800 mg of R-lipoic acid BID, looks interesting.
At the same time, the administration of DCA looks promising. It is reported that R-lipoic acid (form of alpha-lipoic acid) reduces the side effects of DCA.
Now my mom takes together DCA (8mg / kg / BID) and R-lipoic acid (800mg / BID).

However, I found an unexpected opinion about this!!! ↓↓↓

https://www.cancertreatmentsresearch.com/dichloroacetate-dca-treatment-strategy/#comment-4502

“The difference between DCA and ALA is that DCA increases the production of ROS already overexpressed in cancer cells, such as chemotherapy to trigger either apoptosis, autophagy or necrosis of cancer cells. ALA on the contrary will tend to reduce the production of ROS to its normal threshold as in a healthy cell, thus triggering apoptosis if the cell detects a corruption of its DNA. In fact the overproduction of ROS, at the first level will lead to DNA corruption (cancerous state), to the next level we have apoptosis, then autophagy and then necrosis. Thus, with chemotherapy, such as DCA, cancer cells are destroyed by increasing their ROS production, but at the same time healthy cells are transformed into cancer cells by increasing their ROS level in the first stage...

DCA and ALA fall into two opposing strategies, DCA acts by citotoxicity like chemotherapy or radiotherapy, ALA acts by bringing the cells back into their normal operating context (normal ROS level for example). ALA is often taken to correct the neurological effects of DCA, but as part of the cancer their actions cancel each other out, so avoid taking them together. When it starts with an anti-cancer treatment citotoxic, after a certain time it will have to be interrupted before it becomes too harmful for the healthy cells and give the relay to the immune system supported by supplements like ALA, HCA, curcumin, vitamin C, etc."

http://treatingglioblastoma.com/treatments/dichloroacetate_DCA.htm
"Incidentally, I have concerns about any chemo patient taking ALA because it is a powerful anti-oxidant and probably increases intracellular glutathione levels in cancer cells, thereby contributing to chemoresistance. In addition, Dr. Michelakis reports that DCA preferentially increases reactive oxygen species (ROS) in cancer, but not healthy cells, which helps induce apoptosis. I have concerns that ALA could also help reduce the effectiveness of DCA."

However, in this article it is written about similar mechanisms of action of DCA and alpha-lipoic acid:
http://crescopublications.org/pdf/CROOA/CROOA-2-019.pdf

"Inhibition of PDK with either α-LA, small interfering RNAs or dichloroacetate (DCA) shifts the metabolism of cancer cells from glycolysis to glucose oxidation. Such metabolic rewiring is effective in reducing cancer cell growth in mice. The efficacy of cytotoxic chemotherapy is enhanced by the combination of α-LA and HCA. Similarly, DCA enhances the efficacy of cytotoxic chemotherapy or radiation therapy."

http://www.portmoodyhealth.com/cancer-centre/integrative-cancer-therapies/intravenous-alpha-lipoic-acid-iv-ala/
"Furthermore, ALA is cofactor of pyruvate dehydrogenase, an enzyme that converts pyruvate to acetyl-CoA, which reduces the formation of lactate. Lactate is produced from glucose in excessive amounts by cancer cells, as a result of altered cell metabolism (a phenomenon known as the Warburg effect). ALA reduces the amount of lactate produced by cancer cells, slowing their growth rate (19,20). In this way, ALA is synergistic with DCA (dichloroacetate) in its ability to alter cancer cell metabolism."

In reports on the treatment of Medicor, DCA is used together with R-lipoic acid.
For example, here:
http://medicorcancer.com/metastatic-ovarian-cancer/
"The patient consented to DCA treatment and was started at 23 mg/kg/day (500mg p.o. b.i.d.), on a cyclic treatment of 1 week on, and 1 week off. She was supplemented with vitamin B1 100mg p.o. t.i.d., and R alpha lipoic acid 300mg p.o. t.i.d."

Stephen also writes in one of his comments:
"Notably, one of the mechanisms of alpha-lipoic acid (inhibition of PDK, pyruvate dehydrogenase kinase) is a mechanism shared with dichloroacetate (DCA)."

Your opinion? Is it possible to combine a high dose of R-lipoic acid and DCA?
Will not they counteract each other?

P.S. An interesting conclusion of this study:
http://www.anaturalhealingcenter.com/documents/Thorne/articles/R-Lipoic12-4.pdf
"In order to significantly extend Cmax and AUC, it is possible to administer three 600-mg RLA doses (as NaRLA) at 15-minute intervals to achieve plasma concentrations similar to those from a slow (20-minute) infusion of LA."
How can we use it? Take 800mg of NaRLA in three doses at intervals of 15 minutes?

Also, because of problems with the stomach, I consider intravenous administration of alpha-lipoic acid. What dose for one infusion should be taken to equal 800 mg of BID NaRLA? And how often to make such infusions? I find different options: daily infusions or 2-3 times a week.

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?