The Warburg "effect" Is, In Fact, A Direct Cause Of Cancer

[SB4]

No, at the end of glycolysis the output is pyruvate and NADH. So, if only glycolysis is working then you get a buildup of pyruvate and NADH in the cytosol and since glycolysis must continue at ALL COST for the organism to survive then pyruvate becomes the emergency oxidant to NADH and this oxidizes NADH back to NAD with lactate being the end product that is then shuttled to liver to be turned into pyruvate again through the Cori cycle. See this link below.
Glycolysis - Wikipedia

So if PDH isn't working well, we get a build up of pyruvate and NADH in the cytosol. This NADH cannot be used for entry into the mitochondrial complex because NADH cannot directly travel into the mitochondria. So the cell produces lactate to free up some of the NAD+ so glycolysis can continue to produce (small amounts of) energy. The lactate then leaves to go to the liver where it is converted to pyruvate and the cycle can continue.

Now, can methylene blue take the H from NADH and in turn produce leucomethylene blue and NAD+? If so can leucomethylene blue travel from the cytosol into the mitochondria directly?

If one where to take dehydroascorbic acid could that act in the same way, reduce NADH build up and transport these H's into the mitochondria for energy?

 

[haidut]

In mice! I know a trial took place (NCT02531919), but the data was never published.



That isn't true Five-Year Survival Observed in Longest Follow-up to Date of Advanced Melanoma Patients Treated with the Combination of Opdivo (nivolumab) and Yervoy (ipilimumab) Even if patients fail those drugs there are other treatment options Updated Results of Studies in Advanced Cervical Cancer and Melanoma Support Long-Term Efficacy of Iovance Tumor Infiltrating Lymphocyte (TIL) Therapy

Right, but those are recent developments especially the immunotherapies. I meant the official position of the American Cancer Society, which still (the last time I checked) ranks metastatic melanoma as "untreatable". They update the "rankings" every 5 years so maybe their opinion on melanoma changed. I will try to find the latest classifications and post them here.

 

[haidut]

Now, can methylene blue take the H from NADH and in turn produce leucomethylene blue and NAD+? If so can leucomethylene blue travel from the cytosol into the mitochondria directly?

If one where to take dehydroascorbic acid could that act in the same way, reduce NADH build up and transport these H's into the mitochondria for energy?

Yes to both, and actually MB and DHA can also oxidize GSH into GSSG and thus raise the GSSG/GSH ratio, which also contributes strongly to an anti-cancer effects as cancer cells' main defense mechanism against apotosis and ROS is that GSH buildup.
https://pubs.acs.org/doi/abs/10.1021/j100159a054
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[ON THE IMPORTANCE OF SEMI-DEHYDROASCORBIC ACID FOR MICROSOMAL ASCORBIC ACID-DEPENDENT NADH-OXIDATION]. - PubMed - NCBI
https://www.ncbi.nlm.nih.gov/pubmed/7844111
https://www.sciencedirect.com/topics/neuroscience/dehydroascorbic-acid (relevant info is in the section called "Vitamins and Nutrition")

 

[SB4]

@haidut Thanks for the links. It is cool that raising GSSG/GSH can help cancer however I am looking to help CFS which has been associated with high ROS, so hopefully it works in the other direction also.

I have quickly read through the links yet still couldn't find anything that said if leucomethylene blue can pick up hydrogens in the cytosol and then move them into the mitochondria to be sent down the complexes. As far as I understand, NADH isn't able to directly cross into the mito, so can leucomethylene blue?

 

[haidut]

@haidut Thanks for the links. It is cool that raising GSSG/GSH can help cancer however I am looking to help CFS which has been associated with high ROS, so hopefully it works in the other direction also.

I have quickly read through the links yet still couldn't find anything that said if leucomethylene blue can pick up hydrogens in the cytosol and then move them into the mitochondria to be sent down the complexes. As far as I understand, NADH isn't able to directly cross into the mito, so can leucomethylene blue?

Yes, it can. We have discussed MB and its reduced forms acting on both Krebs cycle and ETC before, so they clearly cross into the mitochondria quite easily. MB can accept and move electrons pretty much anywhere in the cell. That's why it is called a "promiscuous electron acceptor".

 

[SB4]

Yes, it can. We have discussed MB and its reduced forms acting on both Krebs cycle and ETC before, so they clearly cross into the mitochondria quite easily. MB can accept and move electrons pretty much anywhere in the cell. That's why it is called a "promiscuous electron acceptor".

Cool, thanks.

 

[oxphoser]

I think FAO is more important as therapeutic target for cancer but FAS is also good to address as it is also overexpressed in every cancer type. Insulin is not as much of a problem as the cancer lobby is making it out to be. It is one of the most potent activators of PDH by inhibiting PDK. This is why insulin therapy for cancer was proposed as early as the 1950s but it never took off because the cancer industry made sure any attempt to treat cancer as metabolic disease was discredited before it had any chance to be proven clinically.
Low-Dose Chemotherapy with Insulin (Insulin Potentiation Therapy) in Combination with Hormone Therapy for Treatment of Castration-Resistant Prostate Cancer
Insulin Potentiation Therapy: A Treatment for Cancer?

Pyruvate is another one and this is one of the reasons we included it in Pyrucet. In general, anything that activates glucose metabolism will inhibit FAO, which insulin is also known to do. Yes, it does increase FAS but that only happens at pathological levels, and even then it is better to synthesize fat than to oxidize it, as far as keeping cancer in check goes. You can take care of keeping FAS low by simply keeping NAD/NADH ratio higher. FAS only gets activated when there is an excess of NADH, which is the case in cancer and increasing NAD/NADH both lowers lactate generation and FAS activation.
Pyruvate dehydrogenase - Wikipedia
"...Phosphorylation of E1 (PDH) by pyruvate dehydrogenase kinase (PDK) inactivates E1 and subsequently the entire complex. PDK is inhibited by dichloroacetic acid and pyruvate, resulting in a higher quantity of active, unphosphorylated PDH.[3] Phosphorylaton is reversed by pyruvate dehydrogenase phosphatase, which is stimulated by insulin, PEP, and AMP, but competitively inhibited by ATP, NADH, and Acetyl-CoA."

By the way, if anyone is interested in getting insulin potentiation therapy for cancer, I noticed that Dr Lodi uses it. You can hear him talk about it on “The Dr Lodi Podcast.” Some differences I noticed with Dr Peat are: Dr Lodi thinks that everyone needs to take iodine and he is into essential fatty acids. He also likes soy. It’s interesting to listen to him though, because he is functioning outside mainstream medicine with its blind application of chemo and radiation to cancer.