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.
Hi Abby,
ReplyDeleteI'm not sure if you've seen this yet, but I wrote a summary of the ALA + hydroxycitrate treatment in the 2017 version of Treatment Options.. available at virtualtrials.com
http://virtualtrials.com/pdf2017/treatment_options_gbm_2017.pdf (see chapter 7)
Alpha-lipoic acid is a co-factor for pyruvate dehydrogenase, and so (like DCA) is expected to help increase the flow of pyruvate into the mitochondria for oxidation and away from conversion to lactate outside the mitochondria (which GBMs typically excel at). However, IDH1-mutant gliomas are known to have distinct metabolic activity compared to IDH1 wild-type GBM. For example, LDHA (lactate dehydrogenase) which is the enzyme that converts pyruvate to lactate, is often silenced in IDH1-mutant gliomas, and overactive in IDH wild-type GBM. So the alpha-lipoic acid treatment *might not* be as useful for IDH-mutant tumors. That is only hypothetical though, and there has been no study published looking at this therapy specifically in IDH1-mutant tumors.
Hydroxycitrate on the other hand is an inhibitor of ATP citrate lyase, an enzyme involved in fatty acid synthesis. ATP citrate lyase (ACLY) is expressed at comparable levels in IDH-mutant gliomas and IDH wild-type GBM, so there's no reason to believe this would be less useful for IDH mutants. In fact, most of the genes involved in fatty acid synthesis are increased in IDH1-mutant tumors, so there is at least a rationale for using the hydroxycitrate. It's also a non-prescription supplement so you wouldn't necessarily need a doctor's approval.
I don't see any reason not to combine this with CCNU.
Lomustine + high DHA fish oil could be a good combination:
Enhanced anticancer properties of lomustine in conjunction with docosahexaenoic acid in glioblastoma cell lines
https://www.ncbi.nlm.nih.gov/pubmed/25526274
Unless he's using perillyl alcohol (which is often in ethanol as a solvent) or would have trouble avoiding products containing alcohol, disulfiram would be worthy of consideration, although it would require a prescription and therefore a doctor's co-operation. There are no less than 5 clinical trials, and more planned, testing disulfiram as a repurposed drug for GBM.
Docosahexaenoic acid and disulfiram act in concert to kill cancer
cells: a mutual enhancement of their anticancer actions
https://www.ncbi.nlm.nih.gov/pubmed/28107189
Thank you, Stephen. I figured it won't hurt to add it but wanted to confirm it can be used with CCNU. I'll read your summary too.
DeleteMy mom takes 30 to 60 minutes before lunch and before dinner:
ReplyDelete1 piece - HCActive Garcinia Cambogia Extract, 500mg (70% hydroxycitric acid)
https://www.iherb.com/pr/Jarrow-Formulas-HCActive-Garcinia-Cambogia-Extract-90-Veggie-Caps/56614
3 pieces - Super R-Lipoic Acid, 240 mg
https://www.iherb.com/pr/Life-Extension-Super-R-Lipoic-Acid-240-mg-60-Vegetarian-Capsules/9824
Naltrexone, 5mg, before bad
She also takes Lomustine+Temozolomide and low-dose Avastin.
No side effects of hydroxycitrate and R-lipoic acid yet!
By the way, the study used this Hydroxycitiric Acid by Solgar:
https://www.iherb.com/pr/Solgar-Hydroxy-Citrate-60-Veggie-Caps/48586
(50% hydroxycitric acid)
Thank you, Semyon. I was wondering if I was purchasing the right supplements. She is taking a total of 720mg/day of ala and 1000mg of hydroxycitrate/day, split between the two meals? Is there a benefit to splitting the dose versus taking all of it at once?
DeleteLaurent Schwartz, the creator of this protocol, recommends taking these supplements as follows:
Delete3 times a day - Hydroxicitrate 500mg (Solgar)
2 times a day (morning and evening) - R-lipoic acid 800 mg.
I wrote letters to him to find out about the food intake, but he no longer consults and treats patients.
Therefore, we simply use the instruction for taking these supplements, where it is written that they should be taken 30-60 minutes before meals.
Also we try to take less additives in the morning, in order to reduce the load on digestion, to avoid nausea.
Dear Stephen,
ReplyDeleteI have a question regarding your comment:
Lomustine + high DHA fish oil could be a good combination: Enhanced anticancer properties of lomustine in conjunction with docosahexaenoic acid in glioblastoma cell lines https://www.ncbi.nlm.nih.gov/pubmed/25526274
As I understand, DHA may be found in many supplements, (for instance, combined with curcumine); But after reading the linked article, I am not sure how to estimate the proper dose, and if the common fish DHA may be really sufficient. (We are at the next round CCNU+TMZ). Would be the DHA supplementation beneficial during the whole, 6 weeks period?
The suggested human dose for omega 3 fatty acids from fish oils for use in cancer patients is: 3 grams daily (DHA + EPA). The actual amount of fish oil consumed would be much higher, and dependent on the DHA and EPA percentage of the fish oil. For example my Carlson's cod liver oil contains 400 mg and 500 mg of EPA and DHA per 5 grams oil (5 mL or one teaspoon). So I would have to take over 16 grams of cod liver oil to get the 3 grams of EPA + DHA, or over three teaspoons daily.
DeleteI would probably take this much DHA + EPA every day, as a regular supplement, during conventional therapies and also as maintenance after conventional treatment has finished.
Thank you Stephen, it's now absolutely clear. We have oil described as containing ~1.0g of DHA+EPA (600mg+400mg), so one large spoon+ makes 3 grams. These oils are attractive supplements, since I believe they should be very safe in such doses.
DeleteTwo short comments to the original post.
ReplyDelete1/ Low dose Naltrexone has been published in some papers. For me this drug is to be discussed in the scope of the psychoneuroendocrine-immune balance, where melatonin and the cannabinergic axis are at the one side and the opioid axis at the other. So combining melatonin + CBD and blocking the opioid axis at the other side is the concept.
2/ Keytruda is an immune modulator. Combination with CCNU seems not very logic because CCNU will block the immune system in this way that there is at the end not much immune system left to modulate.
If I understand correctly, one should not combine naltrexone and melatonin?
DeleteThanks for the input!
Same question. We take at night 20mg Melatonin and 5mg Naltrexone in the form of powder in water.
DeleteThe psychoneuroendocrine‑immunotherapy of
Deletecancer: Historical evolution and clinical results
https://www.ncbi.nlm.nih.gov/pubmed/28567065
According to this paper, anti-cancer immunity is inhibited by opioids via the mu-opioid receptor. According to this paper, administration of (standard high dose) naltrexone, a mu-opioid antagonist, would work co-operatively with melatonin.
Low-dose naltrexone temporarily blocks opioid receptors, causing the body to increase production of met-enkephalin (opioid growth factor), which is primarily a delta-opioid agonist and seems to have beneficial immune effects in tumor-bearing mouse models (see my summary of one such study on this page: http://astrocytomaoptions.com/re-educating-the-immune-system/
So there are two competing theories here:
1) high (standard) dose naltrexone to block the mu-opioid receptor throughout the day and reverse its immunosuppressive effect
2) low dose naltrexone to increase the body's production of the delta-opioid agonist met-enkephalin, with its beneficial and anti-cancer effects
Either way, I don't see a reason why naltrexone would have to be avoided if using melatonin. I understood SVG's comment as supporting the use of higher (standard) dose naltrexone as a mu-opioid blocker, as suggested in the Lissoni paper.
Adding to the competing theories and viewpoints is the use of methadone, a mu-opioid agonist (not inhibitor) in Germany with apparently successful results, at least in some anecdotal cases.
DeleteAccidentally found this research naltrexone in a low dose with the participation of 100 patients with brain tumors. The results speak only of the negative effect of naltrexone...
Delete2015 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639177/
"At 16 weeks, LDN patients reported a significantly greater increase in sleepiness from baseline compared to placebo (p = 0.0088). Adverse events were seen in similar frequencies for LDN and placebo. Of note, overall survival did not significantly differ between treatment groups. While LDN is safe to administer, LDN has no effect on QoL, fatigue, cognition, or survival, but may increase sedation, in HGG patients."
This trial was primarily looking at effect on quality of life.
Deletehttps://clinicaltrials.gov/ct2/show/NCT01303835
"Primary outcome measure: Effects of Low-dose Naltrexone Versus Placebo on Change in Quality of Life (QoL) in High-grade Glioma Patients"
The trial wasn't designed to show survival differences, but still, these results make it sound like it doesn't have much of an effect as a single agent combined with standard therapy.
Very interesting article about the treatment of another type of cancer with IV alpha-lipoic acid, IV vitamin C, hydroxycitrate and naltrexone low dose.
ReplyDelete2017 http://journals.sagepub.com/doi/10.1177/1534735417747984
2017 https://www.ncbi.nlm.nih.gov/pubmed/29086681
ReplyDeleteStrange, it is written here that:
"alpha lipoic acid at doses equal or larger than 1200 mg/die was associated with nausea and vomiting in a large number of patients"
However, in the protocol "Metabloc" it is recommended to take 1600 mg of R-lipoic acid per day. Nausea and vomiting were not recorded.
My mom also takes 1600mg of R-lipoic acid a day without side effects.
This comment has been removed by the author.
ReplyDeleteThis article reports on the synergy of R-alpha-lipoic acid and acetyl-L-carnitine.
ReplyDeleteCan it be useful at glioblastome?
2008 https://www.ncbi.nlm.nih.gov/pubmed/18026715
"We conclude that the combination of LA and ALC may act as PPARG/A dual ligands to complementarily promote mitochondrial synthesis and adipocyte metabolism."
And one more article:
Delete2012 https://www.ncbi.nlm.nih.gov/pubmed/23060917
https://www.spandidos-publications.com/10.3892/etm.2012.556
"It, therefore, appears that carnitine has antioxidant actions in normal cells but induces senescence, which may be regarded as an opposite phenomenon, in glioblastoma cells. ...Carnitine could, therefore, represent an attractive alternative therapy for glioblastoma."
My mom takes 2 months every day 1600mg of R-lipoic acid. Platelets dropped to 70,000. Perhaps this is the influence of R-lipoic acid (
ReplyDelete2017 https://www.ncbi.nlm.nih.gov/pubmed/28984160
"...high-dose ALA could induce autophagy in platelets through modulating the activity of class III PtdIns3K, which was associated with decreased count of circulating platelets and shortened lifespan of platelets."
Interesting blog about the protocol MetaBloc and Laurent Schwartz:
ReplyDeletehttp://silicium.blogspirit.com/dr-schwartz/
History of the treatment of a patient with glioblastoma on the MetaBloc protocol.
ReplyDeletehttps://www.francetvinfo.fr/sante/cancer/cancer-un-nouveau-traitement-a-partir-du-metabolisme_1894729.html
The open question: how much to take capsules Solgar, Hydroxycitrate, 500mg?
3 or 6? 6 capsules contains 1500mg Hydroxycitrate!
Another story of a woman with glioblastoma, cured by the MetaBloc protocol:
ReplyDeletehttp://www.cancer-et-metabolisme.fr/glioblastome/
"- sodium R Lipoate: dose 8 capsules / day Morning Midday Evening and Sunset
- Hydroxicitrate acid: 6 capsules / day Morning Noon in the evening"