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

[GAF]

https://www.amazon.co.uk/Gelum-4261944-Drops-30-ml/dp/B00E5A362U

 

[haidut]

Gelum Drops: reducing lactic acid, increasing hemoglobin and lymphocytes - Blog: Cancer Treatments - from Research to Application

Anybody know what these are? German product. Idealabs?

I have no idea how a product containing L-lactic acid is supposed to lower endogenous lactate producttion...If somebody has an explanation or translation from German then I am all ears.

 

[Obi-wan]

Inaut, I would say also, "what do I really know" ? It is very difficult to decide what path is right, or what is wrong, and clinical evidence is worth a lot when you are faced with that decision. Sigh. There just aren't many cases of haidut's seemingly simple approach ("Break the estrogenic vicious cycle, do NOT restrict glucose, inhibit FAO, and it should go away on its own or at the very least shrink to the point where the immune system can handle it.") let alone with overwhelmingly successful results. Who among us is brave enough to be the first? Obi-wan has been trying various approaches for a while, and I am just starting down that path.

Anyway, I think these drugs may act in multiple, even conflicting ways. For example, Metformin increases AMPK which suppresses SREP-1c, and according to one study "SREBP-1c in the intestine is positively regulated by insulin and negatively by AMPK, and is able to upregulate enzymes, such as acetyl-CoA carboxylase (ACC1) and fatty acid synthase (FAS), which are involved in denovo fatty acid synthesis ". The study also has this interesting chart:

Further down this article looks a mechanisms of statins, and mentions Atorvastatin may block insulin prodution... "Atorvastatin treatment of rat INS-1 β cells induced inhibition of insulin synthesis by inhibiting farnesyl pyrophosphate ester (FPP, an intermediate in mevalonate and non-mevalonate pathways), which may inhibit a chain of proteins that communicates signals from the receptor to the nucleus and is called the Ras pathway (Ras/Raf/ERK/CREB) [124]. Inhibition of this pathway leads to inhibition of promoter activity of the insulin gene and to a decrease of insulin secretion [124]. "

Perhaps some of these actions outweigh the negative increase in lactic acid etc. in cancer therapy. Surely the diet/lifestyle advice could be tailored to address some of the other aspects, like keeping PUFA super low, and the calcium/phosphorous ratio high.

Wow, @LucyL this study at Actions of metformin and statins on lipid and glucose metabolism and possible benefit of combination therapy was very informative. I can see why the Care Oncology Clinic use this combination of Metformin and Atorvastatin. The phenotype of prostate cancer, breast cancer, and others is heavy on Lipid synthesis which this drug combo should minimize. Prostate cancer is considered hormone driven by Androgens but Androgens just create lipid synthesis. Androgen depravation works until the cancer cells decide on de novo lipid synthesis. Hopefully the COC cocktail will finally knock down my high PSA since I am now castrate resistant.

 

[haidut]

Wow, @LucyL this study at Actions of metformin and statins on lipid and glucose metabolism and possible benefit of combination therapy was very informative. I can see why the Care Oncology Clinic use this combination of Metformin and Atorvastatin. The phenotype of prostate cancer, breast cancer, and others is heavy on Lipid synthesis which this drug combo should minimize. Prostate cancer is considered hormone driven by Androgens but Androgens just create lipid synthesis. Androgen depravation works until the cancer cells decide on de novo lipid synthesis. Hopefully the COC cocktail will finally knock down my high PSA since I am now castrate resistant.

You can achieve the same anti-lipid effects and blockade of FAS with much lower risk by using orlistat. No need to take CoQ10-depleting statins of acidosis-inducing metformin. And yes, orlistat was tested specifically on cancer so it is not something purely theoretical.
https://raypeatforum.com/community/threads/cancer-cells-addicted-to-fat-and-use-fat-oxidation-for-survival.7639/
https://raypeatforum.com/community/threads/achilles-heel-of-cancer-found-its-addiction-to-fat.10537/

 

[LucyL]

Targeting acidity in cancer and diabetes.
Gillies RJ1, Pilot C2, Marunaka Y3, Fais S4.
Author information

Abstract
While cancer is commonly described as "a disease of the genes", it is also a disease of metabolism. Indeed, carcinogenesis and malignancy are highly associated with metabolic re-programming, and there is clinical evidence that interrupting a cancer's metabolic program can improve patients' outcomes. Notably, many of the metabolic adaptations observed in cancer are similar to the same perturbations observed in diabetic patients. For example, metformin is commonly used to reduce hyperglycemia in diabetic patients, and has been demonstrated to reduce cancer incidence. Treatment with PI3K inhibitors can induce hyperinsulinemia, which can blunt therapeutic efficacy if unchecked. While commonalities between metabolism in cancer and diabetes have been extensively reviewed, here we examine a less explored and emergent convergence between diabetic and cancer metabolism: the generation of lactic acid and subsequent acidification of the surrounding microenvironment. Extracellular lactic acidosis is integral in disease manifestation and is a negative prognostic in both disease states. In tumors, this results in important sequela for cancer progression including increased invasion and metastasis, as well as inhibition of immune surveillance. In diabetes, acidosis impacts the ability of insulin to bind to its receptor, leading to peripheral resistance and an exacerbation of symptoms. Thus, acidosis may be a relevant therapeutic target, and we describe three approaches for targeting: buffers, nanomedicine, and proton pump inhibitors.

----------------------
Unfortunately I can't get the full text.

 

[Obi-wan]

You can achieve the same anti-lipid effects and blockade of FAS with much lower risk by using orlistat. No need to take CoQ10-depleting statins of acidosis-inducing metformin. And yes, orlistat was tested specifically on cancer so it is not something purely theoretical.
https://raypeatforum.com/community/threads/cancer-cells-addicted-to-fat-and-use-fat-oxidation-for-survival.7639/
https://raypeatforum.com/community/threads/achilles-heel-of-cancer-found-its-addiction-to-fat.10537/

Just started taking Orlistat...should be a home run with Mildronate

 

[haidut]

Targeting acidity in cancer and diabetes.
Gillies RJ1, Pilot C2, Marunaka Y3, Fais S4.
Author information

Abstract
While cancer is commonly described as "a disease of the genes", it is also a disease of metabolism. Indeed, carcinogenesis and malignancy are highly associated with metabolic re-programming, and there is clinical evidence that interrupting a cancer's metabolic program can improve patients' outcomes. Notably, many of the metabolic adaptations observed in cancer are similar to the same perturbations observed in diabetic patients. For example, metformin is commonly used to reduce hyperglycemia in diabetic patients, and has been demonstrated to reduce cancer incidence. Treatment with PI3K inhibitors can induce hyperinsulinemia, which can blunt therapeutic efficacy if unchecked. While commonalities between metabolism in cancer and diabetes have been extensively reviewed, here we examine a less explored and emergent convergence between diabetic and cancer metabolism: the generation of lactic acid and subsequent acidification of the surrounding microenvironment. Extracellular lactic acidosis is integral in disease manifestation and is a negative prognostic in both disease states. In tumors, this results in important sequela for cancer progression including increased invasion and metastasis, as well as inhibition of immune surveillance. In diabetes, acidosis impacts the ability of insulin to bind to its receptor, leading to peripheral resistance and an exacerbation of symptoms. Thus, acidosis may be a relevant therapeutic target, and we describe three approaches for targeting: buffers, nanomedicine, and proton pump inhibitors.

----------------------
Unfortunately I can't get the full text.

Despite the abstract mentioning metformin, the actual study has no discussion of metformin whatsoever. What it does discuss is how lactic acid is a primary driver of tumor growth (as the abstract hints) and the various methods for combatting the acidity in cancer. Here is one good subsection on baking soda.
"...The most direct approach to neutralize tumor acidity is the administration of oral buffers, such as NaHCO3. In animal models oral buffers, such as sodium bicarbonate, specifically increase tumor pH without affecting systemic pH balance, and potently inhibits experimental or spontaneous metastases 106-109 . Indeed, a commercially available mix of bicarbonate and carbonate salts (i.e. BasenPulver, Pascoe Germany) was able to control melanoma growth consistent with a buffering effect at both tumor and systemic level 110. These responses are due to buffer effects rather than to bicarbonate per se, as other buffers also work 111,112 . Further, effects are also manifest in genetically engineered mouse cancer models (GEMMs). For example, in the TRAMP prostate model, the initiation of buffer therapy at 4 weeks of age prevents emergence of cancer 113, but if administered after 10 weeks (after tumors are extracapsular), it has no effect on the primary tumors, but completely inhibits metastases 114,115 ."

So, if I am reading this correctly, the study says that a commercially available baking soda product can completely control melanoma growth, prevent cancer in genetically cancer-guaranteed mice, and completely prevent metastases from such cancer(s). At the same time we are being told that nothing can really be done for metastatic melanoma, which is the second deadliest cancer (after pancreatic), and that baking soda treatment of cancer is a scam.
I pity all doctors (and public health officials) when this finally becomes common/public knowledge...At some point, some news media will pick this up and decide to run with it. There is too much newsworthiness (read: money) in being the first to condemn the scam and somebody will do it...and it won't be pretty.

 

[jb116]

For what it's worth, I've seen that whole paper and they start to push the Proton Pump Inhibitors eventually.

They arrived at the extracellular problem with cancer, then concluded PPI would be of use. Embarassing.

 

[haidut]

For what it's worth, I've seen that whole paper and they start to push the Proton Pump Inhibitors eventually.

They arrived at the extracellular problem with cancer, then concluded PPI would be of use. Embarassing.

True, good catch
I ignored that part as they do not even provide good case for the PPI, and they have never been shown to buffer acidity or improve acidosis in vivo. The text just keep saying PPI "should work".
I think it still helps that even a biased study like this says baking soda works. There will always be a push from studies to use pharma drugs, but as long as the discussion is steered towards cancer being metabolic disease, it is a net positive for society, IMHO.

 

[jb116]

True, good catch
I ignored that part as they do not even provide good case for the PPI, and they have never been shown to buffer acidity or improve acidosis in vivo. The text just keep saying PPI "should work".
I think it still helps that even a biased study like this says baking soda works. There will always be a push from studies to use pharma drugs, but as long as the discussion is steered towards cancer being metabolic disease, it is a net positive for society, IMHO.

Very surprising them referring to baking soda, caught me off guard, have to admit lol

 

[LucyL]

Just started taking Orlistat...should be a home run with Mildronate

Are you taking Orlistat along with the COC protocal?

 

[LucyL]

This study
Targeting metabolic flexibility by simultaneously inhibiting respiratory complex I and lactate generation retards melanoma progression
used oxamate and DCA to inhibit lactic acid induced by metformin. Anyone know what oxamate & DCA are?

 

[haidut]

This study
Targeting metabolic flexibility by simultaneously inhibiting respiratory complex I and lactate generation retards melanoma progression
used oxamate and DCA to inhibit lactic acid induced by metformin. Anyone know what oxamate & DCA are?

Oxamate is an LDH inhibitor, so it lowers lactic acid synthesis (but has toxicity). DCA is a PDK inhibitor and as such activator of PDH. We have discussed the latter many times on the forum and Peat has written about it too. Just search forum for DCA. It also has toxicity and is carcinogenic when used chronically. Thiamine is likely a safer substitute for DCA and MB is a likely a safer substitute for oxamate.
https://raypeatforum.com/community/threads/thiamine-acts-similarly-to-dca-and-may-be-helpful-in-cancer.3895/
https://raypeatforum.com/community/threads/thiamine-treats-cancer-in-humans-its-deficiency-may-cause-cancer.21350/
The effects of methylene blue (MB) on tumor respiration

 

[Obi-wan]

Are you taking Orlistat along with the COC protocal?

Just started. Yes I take other supplements along with the COC protocol. I follow Jane McLellands metro map

 

[LucyL]

This clinic in Canada uses DCA in cancer treatment, and mentioned caffeine interferes with its effects. "After conducting a limited review of our DCA patients, we have noted that a few patients with high tea/caffeine consumption (> 10 cups per day) have shown no response to DCA. Also many patients who have shown an excellent response to DCA do not take tea/coffee or caffeine or take it in minimal amounts."

Caffeine has its own positive effects on tumors, would it also interfere with high-dose Thiamine?

 

[Cirion]

@Obi-wan I am sure you have tried a lot of things already, but have you been in touch with Nathan Hatch? He cured his cancer without any prescription drugs (as far as I can remember) but did use a few metabolic aids like thyroid, pregnenolone, progesterone etc...

And how is your environment? I think living in a perfect environment like high altitude/warm tropical beach/low to zero man made EMF's etc would be necessary for a smooth recovery from cancer.

You may have tried all that already, just throwing some thoughts out though. Good luck man.

 

[Obi-wan]

Wikipedia on Mildronate (Meldonium):

"To ensure a continuous guarantee of energy supply, the body oxidizes considerable amounts of fat besides glucose. Carnitine transports activate long-chain fatty acids (FA) from the cytosol of the cell into the mitochondrion and is therefore essential for fatty acid oxidation (known as beta oxidation). Carnitine is mainly absorbed from the diet, but can be formed through biosynthesis. To produce carnitine, lysine residues are methylated to trimethyllysine. Four enzymes are involved in the conversion of trimethyllysine and its intermediate forms into the final product of carnitine. The last of these 4 enzymes is gamma-butyrobetaine dioxygenase (GBB), which hydroxylates butyrobetaine into carnitine.

The main cardioprotective effects are mediated by the inhibition of the enzyme GBB. By subsequently inhibiting carnitine biosynthesis, fatty acid transport is reduced and the accumulation of cytotoxic intermediate products of fatty acid beta-oxidation in ischemic tissues to produce energy is prevented, therefore blocking this highly oxygen-consuming process.[4] Treatment with meldonium therefore shifts the myocardial energy metabolism from fatty acid oxidation to the more favorable oxidation of glucose, or glycolysis, under ischemic conditions. It also reduces the formation of trimethylamine N-oxide (TMAO), a product of carnitine breakdown and implicated in the pathogenesis of atherosclerosis and congestive heart failure.

In fatty acid (FA) metabolism, long chain fatty acids in the cytosol cannot cross the mitochondrial membrane because they are negatively charged. The process in which they move into the mitochondria is called the carnitine shuttle. Long chain FA are first activated via esterification with coenzyme A to produce a fatty acid-coA complex which can then cross the external mitochondrial border. The co-A is then exchanged with carnitine (via the enzyme carnitine palmitoyltransferase I) to produce a fatty acid-carnitine complex. This complex is then transported through the inner mitochondrial membrane via a transporter protein called carnitine-acylcarnitine translocase. Once inside, carnitine is liberated (catalysed by the enzyme carnitine palmitoyltransferase II) and transported back outside so the process can occur again. Acylcarnitines like palmitoylcarnitine are produced as intermediate products of the carnitine shuttle.

In the mitochondria, the effects of the carnitine shuttle are reduced by meldonium, which competitively inhibits the SLC22A5 transporter. This results in reduced transportation and metabolism of long-chain fatty acids in the mitochondria (this burden is shifted more to peroxisomes). The final effect is a decreased risk of mitochondrial injury from fatty acid oxidation and a reduction of the production of acylcarnitines, which has been implicated in the development of insulin resistance.[8][9] Because of its inhibitory effects on L-carnitine biosynthesis and its subsequent glycolytic effects as well as reduced acylcarnitine production, meldonium has been indicated for use in diabetic patients."

What a great product for FAO inhibition!

 

[GAF]

Maybe mildronate is helping me in more ways than I can feel. Hmmm.

 

[Obi-wan]

@Obi-wan I am sure you have tried a lot of things already, but have you been in touch with Nathan Hatch? He cured his cancer without any prescription drugs (as far as I can remember) but did use a few metabolic aids like thyroid, pregnenolone, progesterone etc...

And how is your environment? I think living in a perfect environment like high altitude/warm tropical beach/low to zero man made EMF's etc would be necessary for a smooth recovery from cancer.

You may have tried all that already, just throwing some thoughts out though. Good luck man.

Thanks @Cirio! Metabolic aids don't work on cancer. A cancer cell has many mitochondria. Many are defective but many are working overtime to meet the energy requirements of the cancer cell. Mitochondria was once considered bacteria that single cell organisms gobbled up. Doxycycline should help get rid of them.

 

[Obi-wan]

Great info on repurposing drugs at read:https://integrativeoncology-essenti...binations-of-supplements-and-off-label-drugs/

List of some of the more popular anticancer compounds:

Dosing information derived from the design and methods sections of published and unpublished clinical studies (main source: ClinicalTrials.Gov)

• Acetazolamide: 250 mg 2 x/day x 1 week, then increase to 500 mg 2 x/day
• Aspirin (low dose, enteric coated aspirin): 81 mg 1 x/day
• Artemisinin or artesunate: (artesunate: 200 mg artesunate 1 x /day, artemisinin: 200-500 mg 1 x/day)
• Berberine: 100-500 mg 2-3x/day (consider a 4-week break every 8-weeks to give the liver a break from this alkaloid compound)
• Beta-Glucan (Beta-1,3/1,6-glucan): 250 mg 3 x/day
• Cannabis oil
• Chloroquine or hydroxychloroquine (hydroxychloroquine: 200 mg 1-2 x/day)
• Chromium (chelated or niacin-bound): 200-1000 mcg 1 /day
• Cimetidine: 400-800 mg 2 x/day
• Clarithromycin: 500 mg 2 x/day
• Curcumin: 1000-4000 mg 2 x/day
• Dichloroacetate “DCA”: 4.0-12.5 mg/kg body weight 2 x/day (more information on dosing: DCA Guide)
• Dipyridamole: 50-100 mg 3 x/day
• **Doxycyline: 100 mg 1 x/day
• Green tea extract “EGCG”: 200 mg 2-3x/day
• Hydroxycitrate: 500-1000 mg 3 x/day (commonly extracted from Garcinia Cambogia)
• Indole-3-carbinol “I3C”: 400-800 mg 1 x/day
• Inositol+IP6: most common dosing is 2-4 grams/day (higher doses used for anxiety and depression: 12-18 grams/day)
• Itraconazole: 200 mg 1-3 x/day
• **Mebendazole: 100 mg 1 x/day
• Melatonin: 20 mg 1 x/day
• **Metformin: 500 mg 2-3 x/day (take with high-quality multi-B-vitamin with methyl B12, methyl folate and thiamine, as metformin can reduce B vitamin absorption)
• Naltrexone (low-dose): 5 mg 1 x/day (LDN Research Trust: start at 1-1.5 mg 1 x/day for 7 days, increase daily dose by 0.5-1.5 mg each week until you reach 4.5-5 mg 1 x/day)
• Niclosamide: 2000 mg 1 x/day (take with oil for better absorption: i.e. omega-3 fish oil, olive oil)
• Non-steroidal anti-inflammatories “NSAIDs” (celecoxib: 200-400 mg 2 x/day; diclofenac: 35 mg 3 x/day; etodolac: 400-800 mg 2 x/day; ibuprofen: 400-800 mg 3 x/day)
• PHY906 (Huang Qin Tang formula: Chinese peony, Chinese jujube, baikal skullcap, and Chinese licorice): 800 mg 2 x/day
• Polydantin (Biotivia Pteromax: 1 pill/day)
• Propranolol: 20-40 mg 2 x/day
• Quercetin: 500 mg 1-2 x/day
• Resveratrol: 20-5000 mg 1 x/day
• Statins (lipophilic statins: simvastatin, lovastatin and atorvastatin; **atorvastatin: 40 mg 2 x/day, or simvastatin: 20 mg 3 x/day; take with vitamins A, D, K resveratrol, olive oil); Bergamot extract appears to have similar statin-like properties and may be an alternative for statin-intolerant patients: 500-1500 mg 1 x /day
• Tetrathiomolybdate “TM” (Induction phase: 40 mg 3 x/day with meals and an additional 60 mg at bedtime. Goal of induction phase is to decrease ceruloplasmin level to 5-15 mg/dL. Once this is achieved, the maintenance phase will begin: 40 mg 2 x/day with meals and an additional 20 mg at bedtime.)
• Ursolic acid: 150 mg 1-3 x/day
• Vitamin C (high-dose intravenous): 50-75 grams intravenous 3 x/week; The Riordan Clinic IV vitamin C (IVC) protocol: “In our experience, the majority of cancer patients require 50 gram IVC infusions 2-3x/week to maintain therapeutic IVC plasma levels (350- 400 mg/dL) . All patients reaching therapeutic range should still be monitored monthly with post IVC plasma levels to ensure that these levels are maintained long term. We advise patients to orally supplement with at least 4 grams of vitamin C daily, especially on the days when no infusions are given.”

**4-Drug COC Protocol™ (Care Oncology Clinic):

• Atorvastatin: 40 mg 2 x/day
• Metformin: 500 mg 2 x/day (start with 500 mg 1 x/day x 2-weeks and increase to 500 mg 2 x/day if tolerated)
• Doxycycline 100 mg 1 x/day
• Mebendazole 100 mg 1 x/day
• Clinical trial reference: https://clinicaltrials.gov/ct2/show/NCT02201381