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Anti oxidant - chemo saga..ref: Daniel's quote from Iver.

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(@nnj925)
Joined: 3 years ago
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Hi all I have Stage 4 Triple Neg Breast Cancer with mets to bone and liver.  I have been taking Ivermecting with chemo (Trodelvy) for about 5 months I worked up to 25mg from 3mg...over 3 months doing 5 days on 2 off then after a couple of months I take 3-4 weeks off. Anyway I read Daniel's article about Ivermectin recently and I saw he said :

"This is a similar story with that of pro-oxidants and anti-oxidants treatment strategies in oncology. No matter which one you pick it will be effective against cancer as long as it is done in a coherent manner, so that the treatments used they are either pro- or anti-oxidants. Same here with Chlorine intracellular accumulation (by Ivermectin) or depletion by scorpion venom. We shoudl chouse either one, or the other but not both at the same time."

So does this mean no antioxidants with TAXANE chemos specifically as we know anti-oxidants would be doing the exact opposite of TAXANE chemos specifically.  BUT what about Carboplatin/ Gemcitabline? Or Trodelvy/ sacituzumab govitecan-hziy. which the mechanisim of action is a Trop-2-directed antibody and topoisomerase inhibitor conjugate drug. It targets the Trop-2 antigen, a humanised monoclonal antibody, expressed on various tumour cells and delivers SN-38, a topoisomerase I inhibitor, to the tumours directly, causing cell death.  Which does not kill cancer like a Taxane?? Can anyone speak to using anti-oxidants with Carboplatin/Gemcitabine and also for Trodelvy?

Thanks,

Nicole


   
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(@daniel)
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HI Nicole,

Thank you for your question.

When I wrote that, I only meant that we need to be coherent and inline with the main mechanism of action we like to build on. If for Ivermectin the main one may be related to increasing the activity of Chloride channels, we do not want to use other compounds (such as scorpion venom) that reduce the activity of the same channels, as we get a reduced net effect. It is about choosing one direction and pushing only in that direction.

I was giving as example the story with anti- and pro-oxidants, as it is similar. We want either to use anti-oxidants or pro-oxidants, and not both at the same time.

Regarding your question about the different chemo in combo with anti-oxidants, there is a simple answer and a more complex answer.

The simple answer is if we do not know exactly the role of Reactive Oxygen Species in the anti-cancer mechanisms of a specific chemo, we better just avoid them (and I will explain below what I mean by that).

The more complex answer is that some chemo are relying on ROS to kill cancer, and some not so much. So we need to understand what is the main anti-cancer mechanisms for each chemo. If we do understand that, and we know we have a chemo that does not rely much on ROS, combining that chemo with anti-oxidants may be even very beneficial. Actually, here it is not my answer that is complex, but the work that has to be done in order to understand well the anti-cancer mechanisms of specific chemo. This is why, there are some clinics around the world claiming positive results with Chemo+Super Antioxidants such as Glutathione.

Now the question is which are the anti-oxidants we should care about they anti-oxidant action and which we should not worry about.

In one of my posts, here https://www.cancertreatmentsresearch.com/modulating-the-yin-and-yang-energy-of-cells-to-fight-cancer-pro-oxidant-strategy/ I discussed and organized the supplements in 3 different groups:

  • super anti-oxidants such as NAC, ALA, Glutathione
  • anti-oxidants (that actually have pro-oxidant action at cancer cell level) such as Curcumin, EGCG, etc.
  • pro-oxidants such as Artemisinin, B17, etc.

The first category, I woudl stop two days before chemo and restart 7 days after but not earlier. The second category, I woudl stop two days before chemo and restart two days after (some clinics even combine them with chemo). The third category, I woudl keep it going while on chemo.

Next to the above, there are some other aspects that have to be considered in order to decide on how supplements and repurposed drugs should be implemented around chemo. One aspect is to consider of they are or not glycolisis inhibitors. The other aspect is to consider if they are Multi Drug Resistance inhibitors. 

I hope one day soon I will have time to write a blog post on this subject as I think is important in putting together an effective treatment strategy to increase the chance for effectiveness of conventional therapies.

Nicole, are you on Gemcitabine and the other drugs, or you asked about these as a more general question?

Kind regards,
Daniel

 


   
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(@nnj925)
Joined: 3 years ago
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Topic starter  

@daniel  Thank you so much for the reply Daniel I am so grateful!!  I am on Trodelvy right now. But I am running out of treatments and my next treatment is going to be the Gem/Carbo combo (if the Trodelvy fails, I scan June 22). Right now I took a 3 week break from the 25mg Ivermectin bc I was going to start a 3 week Artemisinin protocol. (and yes it does require a 25mg of Iron HEME supplement with it but I am only taking that every other night and also) the Artemisinin I got is lipsomal form.  I will also be taking Vit C 500mg and Sodium buyrate too and Artesumate .....   

I did post the Mechanism of Action for the Trodelvy..but and I know Ivermectin or Artemisinin would play well with it..but I do wonder if Astaxanthin would be ok with this...and also with Gem/Carbo...


   
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(@nnj925)
Joined: 3 years ago
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Topic starter  

@daniel Sorry Daniel I forgot to ask...so the second catagory you mentioned "anti-oxidants (that actually have pro-oxidant action at cancer cell level) such as Curcumin, EGCG, etc." Would this include Melatonin and Astaxanthin?  I want to also add in high dose 180mg or higher of melatonin but not with the Artemisinin as I read this "“Melatonin inhibits (prevents) ferroptosis which is the process of oxidizing iron which is how artemisinin kills cancer cells meaning melatonin protects cells from ferrroptosis which is why you do not want to take melatonin while doing artemisinin.”   but would like to add it after (if I stay on Trodelvy as I do not know the mechanisim of Gem/Carbo... Any thoughts?       


   
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johan
(@j)
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Posted by: @nnj925

@daniel   I was going to start a 3 week Artemisinin protocol. (and yes it does require a 25mg of Iron HEME supplement with it but I am only taking that every other night and also) the Artemisinin I got is lipsomal form.  I will also be taking Vit C 500mg and Sodium buyrate too and Artesumate .....   

 

Hello, Artemisinin does not require iron supplementation. 

https://www.spandidos-publications.com/10.3892/ijo.2019.4921

"It has been a matter of discussion among veterinarian physicians and alternative practitioners, whether or not supplementation of iron is beneficial for the activity of artemisinin. The role of heme has been discussed for the antimalarial activity of artemisinin and its derivatives (57,58). In the context of cancer, we previously reported that Ferrosanol® and holotransferrin increase artesunate-induced cytotoxicity and apoptosis in leukemia and astrocytoma cells up to 10-fold. These effects were reversed by anti-TfR monoclonal antibody RVS10, which competes with transferrin for binding to TfR. While the TfR expression ranged between 48 and 95% in tumor cell lines, normal peripheral mononuclear blood leukocytes revealed ≤1.3% TfR positivity, indicating that artesunate may exert tumor specific effects at least to some extent, because of the preferential TfR expression in tumor cells (59).

In a subsequent study, we investigated a total of 36 cell lines of different tumor types for their response to treatment with artesunate alone or in combination with Ferrosanol® (60). This revealed that artesunate plus Ferrosanol® enhances cytotoxicity compared with artesunate alone in the majority of cell lines; however, 11 cell lines did not demonstrate increased apoptosis and nine lines exhibited a decrease in apoptosis following the combined drug treatment compared with artesunate-treatment alone. It is understood that iron acts as co-factor for proliferation-related enzymes (61). Therefore, Ferrosanol® may induce rather than suppress the proliferation of these nine cell lines. Based on these in vitro data, it cannot be reliably recommended that iron should be added as a supplement to artemisinin-type treatment in veterinary or human cancer therapy. The results of the present study revealed that the blood iron content was not associated with survival times after A. annua therapy, while the TfR content inside the tumor was."

 


   
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(@nnj925)
Joined: 3 years ago
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Topic starter  

@j  "This revealed that artesunate plus Ferrosanol® enhances cytotoxicity compared with artesunate alone in the majority of cell lines" ummm so I didn't understand alot of the tech.stuff in what you posted but I did get the part i just quoted..and to me...that says that the MAJORITY did better with adding the iron.... I do know some people that didn't add the iron (also stage 4) and they said it didn't work...so....it makes me wonder...plus most of the iron is not bioavailable anyway I think they say like 75%...so if I am only taking a 25mg supplement every other night for 3 weeks...I don't think it will hurt...but I am not a doctor or a biochemist etc...so just my thoughts.


   
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johan
(@j)
Joined: 5 years ago
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@nnj925 

just adding the above information, pointing to the fact that iron supplementation is not required, so people don't get the wrong idea. That's all. In some cases, it may be helpful in other cases iron supplementation may make things worse. 


   
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(@nnj925)
Joined: 3 years ago
Posts: 7
Topic starter  

@j I understand. I was originally worried about taking it but again most of it is not even bioavailable and im only taking 25mg every other night for 3 weeks only (during the protocol) so I am going to do it. To me that probably means I am only really getting like 10mg...if that.

 


   
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johan
(@j)
Joined: 5 years ago
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@nnj925 I really hope it works wonders for you, Nicole. There are a few other synergies in relation to artemisinin and artesunate you might want to look into. You mentioned butyrate, and there's Honokiol/Magnolol, Allicin, and artesunate with ellagic acid.


   
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(@nnj925)
Joined: 3 years ago
Posts: 7
Topic starter  

@j So for the Arte. protocol I am doing : 21 days of 1,000 or 1,200 mg of liposomal artemisinin with one to two capsules of sodium butyrate and 1-2 capsules of piperine taking everything with grapefruit juice. Iron every other night during those 21 days (1 capsule an hour or so before dinner or 1 hour or so after dinner with 500 mg of vitamin C) While doing the liposomal artemisinin, pulse 500 mg of artesunate ( 4 days on and 3 days off). I will take the artesunate with the liposomal artemisinin, sodium butyrate and piperine during the days that you are on artesunate. 

After the 3 weeks I will take 3 weeks off.  During the 3 weeks off I am going to rotate back in my 25mg of Ivermectin 5 days on 2 off.  Then I am also adding in (to take everyday for 4 week and 1 week off each month) of LDN. 

 


   
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johan
(@j)
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@nnj925 sounds good! 


   
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