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?

Tom Wangerin - Cocktail Profile and Questions

Hi all,

Although this is my first post, I have been reading every minute of every day. Such an amazing wealth of information on here. I would appreciate any advice on our current course of action and opinions on our cocktail.

My dad was diagnosed with a grade IV GBM. He had surgery on 11/23/16 with 95% resected.

Lab Results:
MGMT Gene Promoter Methylation – Detected.
Percent of MGMT Methylation is 36.19%
IDH1/2 Mutation – Not detected
Positive for 1p Deletion

• Completed his first round of daily chemo/radiation on 1/19/17.
• Our first image was taken on 2/3/17. We had our first consultation with the UCSF Tumor Board (Dr. Butowski) on 2/7/17.
• Tumor had not seemed to grow in size any, but did morph into a new shape/area which is scary to see. Next image in 2 months.

Currently taking:
·       Dexamethasone (Decadron) – He is currently taking 4mg/day but we are doing what we can to wean him off. We have been told this will dictate whether we go on Avastin.
·       Eliquis – blood thinner - 5mg twice a day
·       Keppra – 500mg twice a day.
·       Bactrim (Antibiotic) – Original oncologist prescribed during chemo.

Supplements:
1:1 CBD/THC – Tincture drops in day, Oil at night.
Probiotics – Sibiotica (K-97)
Curcumin - Nutrivene Longvida 1000mg - 1x Morning 1x Night (1000-2000mg daily)
Fish Oil - Vital Nutrients - EPA-720mg, DHA-480mg per cap - 1x Morning
Boswellia Serrata Extract - Progena Meditrend – Currently taking (3) 333mg daily.
Melatonin - Vital Nutrients - 10mg/cap - 1x at Night (eventually will do 20mg)
Mushroom Extracts - Turkey Tail (Coriolus), Maitake D-faction, and Reishi each once a day.
Berberine - Vital Nutrients - 200mg/cap – starting with 1x day, soon 3/day.
Debating whether to add - Resveratrol and Green Tea Extract

Our NO was okay with all and suggested adding Cronaxal. I’ve struggled to find much convincing information out there, but I do trust our NO. Now the question is to use Cronaxal (expensive and high dosage) or get Sulfasalim (which Stephen ranked pretty high on his spreadsheet).
I read that this can benefit those that are NOT IDH mutated (which is us).

Genetic Testing
We are getting the tumor tested from Foundation One for more details – once we make sure there is enough tumor for them to test, and have some left for potential clinical trials. I’m keeping an eye out for EGFR, p53, VDR, HIF-1.
Any thoughts here?

Hoping for some advice in a selection of the following:

**Vitamin D3 – In some cases Vitamin D3 caused proliferation in some patients (Stephen W speaks of this: http://astrocytomaoptions.com/supplements/). Our NO was okay w/ Vitamin D3. Would checking his VDR receptor be of value for determining this, or is it safe (and potentially beneficial) to take 5,000-10,000iu daily regardless of tumor type?

I was very excited about a few of the prescription drugs below, but our NO was certain that none of them get past the blood brain barrier while taking doses safe for humans. We are still willing to give a few of them a shot, but I’m struggling to decide which combinations.

·       **Chloroquine Phosphate – (if overexpressing the EGFR protein or p53 status is unmutated) & **DCA - Sodium Dichloroacetate –(if HIF-1 is expressing) http://astrocytomaoptions.com/targeting-tumour-metabolism/
·      **Disulfiram – This drug looks like it has amazing potential.
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=707

·       **Sildenafil & Celebrex: can work synergistically for both getting past blood brain barrier, anti-tumor qualities, and Celebrex potentially helping with a bit of edema.
http://onlinelibrary.wiley.com/doi/10.1002/jcp.24843/abstract

·      VT-122 (Etodolac & Propranolol) – with low dose daily TMZ schedule. This had great results. Any reason why more people aren’t doing this themselves?
(http://meetinglibrary.asco.org/content/151704-156)

·       CUSP9 – Looks like an amazing plan. I am yet to read of any results but I know many are starting to replicate this cocktail on their own.
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=2408

Current Plan:

I.         TMZ Schedule – Because he is MGMT methylated it was an easy decision to go forward with the monthly TMZ cycles. All of our docs have insisted on the high dose 5days/month schedule rather than a metronomic schedule, regardless of whether EGFR is over expressed. Thoughts?
https://academic.oup.com/jnci/article/107/5/djv041/891259/EGFR-Amplified-and-Overexpressing-Glioblastomas

II.         Optune Machine – The UCSF board feels it’s not as beneficial as some of the studies make it out to be, and with it being such a pain to wear for the rest of your life… it’s not that easy of decision even with insurance coverage. I’m undecided here.

III.         Prescriptions with TMZ/Avastin - If you had to pick one prescription duo to take with TMZ and one prescription duo to take with Avastin to make them more effective which would you pick?

Thank you all for pitching in. This journey has been life changing, but manageable with the help you all bring.

Celebrex control edema? also question about boswilla

Hi all,

I come from China,this blog is wonderful to help my GBM wife.I want to start with a quick question. Stephen,i saw in the library excel that celebrex can help reduce edema,but i can not find related study in the library, do you have it?

I read the study on boswilla serrata control edema pretty well, just want to confirm is that still the best way?

Regards
Roy

Cronaxal

Has anyone tried Cronaxal or might have any info regarding whether it is worth trying? Thanks
http://www.cronaxal.com

Glutamate?

Hello,

there hasn't been much written about the role of glutamate in gliomas, so I was wondering if anyone had looked into it before? It caught my attention some time ago when someone posted a link to "medical food" Cronaxal, which "is a combination of oxaloacetate and ascorbic acid (vitamin C). Oxaloacetate reduces Glutamate levels in the brain in multiple laboratory animal tests.  Glutamate overproduction is directly tied to the growth of malignant gliomas, their invasiveness, and their ability to destroy neighboring brain tissue.  Patients with Glial Tumors have an impaired capacity to metabolize glutamate due to the high amount of glutamate produced by the tumor itself.  Oxaloacetate helps to metabolize glutamate to alpha-ketoglutarate."

Anyway, search on pubmed does return some hits on glutamate and glioma, for example Glutamate and the biology of gliomas (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107875/) where it states: "Glioblastoma tumors release Glu to enhance their highly malignant behavior, and that Glu release via system x_c^- and the excess extracellular Glu this system imparts a survival advantage by promoting resistance to apoptosis and by promoting glioma proliferation and invasion. In fact, the invasive nature of gliomas enhanced by Glu release is one of the most important limitations to effective disease control; experience demonstrates that more than 80% of glioblastoma recurrences occur within 2-3 cm of the original resection cavity. Successful treatment of malignant gliomas requires recognition of Glu and its receptors as potential targets and novel approaches modulating their influence are needed to improve upon existing ineffective therapies."

At the end of the article there are some suggestions for targeting glutamate with repurposed drugs, but I also found some supplements that could do that in some degree (like theanine, N-acetylcysteine and glycine). Anyone tried this approach to complement the cocktail?

 

CBD

hello everybody,

I read that many of you have cannabis oil in your cocktail.
Is CBD without THC also effective? dont quite understand the posts I read about it..
My dad takes CBD drops.
Thanks
kind regards,
Lycka

Update on Minjung's status

Hi everyone,
Hope all of you and your beloved ones are doing well.

Here's an update of my fiance's situation.
Minjung's been very ill for the last few weeks. She had finished radiation about a month ago, but she started to have minor but constant seizures and some problems with body coordination. She's been and still is being treated with steroids but things are just getting worse... and now she is unable to open her eyes (she still can see if we force open her eyelids).
3 days ago, she had another surgery because the doctor thought her shunt wasn't working properly. When she woke up, she could open her eyes and we all thought things were going in the right direction.. until the next day when she went back to how she was before the surgery.
Also, the current anti-seizure med (Keppra) is clearly not working at all.
So we asked the staff to tell the doctor to prescribe valproic acid as her anti-seizure med today. We'll see how the doctor responds to our request...

We want her to start Temodal and cocktail therapy as soon as possible, but every time we bring that up, the doctor keeps saying she's not ready at all for chemotherapy. We're even considering switching to other hospital. My worst fear is that Minjung may not even have a fair chance of battling this disease, which to me was the cocktail approach.



Best,
Hyunsun