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2-dg metformin combination as a cancer prevention/management strategy

2-dg ketosis cancer longevity ampk metformin caloric restriction

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#1 rhearon

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Posted 11 August 2017 - 09:59 PM


Metformin, in combination with 2-DG has been shown in numerous studies to inhibit cancer growth as well as positively impact autoimmune disease. Because it seemingly relies on the Warberg effect to do so, and because it appears to do so without significant side effects - it seems to me that periodic application (every few years?) in elderly and at risk individuals might be a viable anti-aging protocol. I do have some experience with it's rather remarkable effects on SLE (lupus).

 

I am considering a 4 week trial of 1500mg Metformin and 30mg 2-dg daily with dosage increases beginning at 500mg/7.5mg an escalating every 3 days for the first 12 days. The goal would be to help slow or halt the growth of undetected tumors. I'm a healthy 60 year old male. Any feedback/thoughts would be appreciated.

 

Most readers are presumably aware of the considerable research showing the diabetes drug metformin's ability to produce a statistically significant increase in lifespan in animal models as well as results showing (probable) positive effect on human lifespan through populations studies.

 

 

The drug 2-DeoxyGlucose (2DG) is a glucose analog that is avidly taken up by cancer cells. It differs from normal glucose only by removal of an oxygen atom from the hydroxyl group at the 2 position. It is readily and preferentially taken up by up any cancer visible via a PET scan (they rely on glucose). While there have been concerns about toxicity and heart damage in humans at high doeses, it is presumed to be safe in studies under 63mg/kg. The upward limit comes from it inducing hypoglycemia at higher dosages - toxicity occuring above 200mg/kg. This is readily reversible with sugar, but still an issue. Using a continuous blood glucose monitor such as freestyle libre seems  like a good idea (not yest FDA approved, but for sale in Europe and on ebay https://www.freestyl...-started.html).

https://www.ncbi.nlm...pubmed/23228990

 

"...increased glucose metabolism is a hallmark of cancer. Thus, most of the major oncogenic events have now been shown to have direct or indirect mechanisms by which they control increased glycolysis in tumor cells under normal oxygen condi- tions (commonly known as aerobic glycolysis), an observation made by Warburg more than 80 years ago (1). 2-Deoxy-D-glu- cose (2-DG) has been found to be uniquely suited to exploit this universal trait as it has been demonstrated to be a powerful agent for blocking and probing increased sugar metabolism in cancer cells (2–5) (Fig. 1). Taking advantage of the increased glucose uptake that occurs in most tumors provides a specificity window that increases the selectivity of this analog (3,5–8). Because of its similarity to glucose, 2-DG inhibits glycolysis, but as chemically it is also 2-deoxymannose it is able to com- pete with mannose in the growing lipid-linked oligosaccharide chain during the initial steps of N-linked glycosylation. This mannose-like property of 2-DG results in misfolded proteins leading to endoplasmic reticulum (ER) stress (3). Thus, 2-DG is a compound that not only naturally exploits increased glucose uptake in tumors but by its structure can induce energy as well as ER stress. These fortuitous attributes have enabled 2-DG to be used to selectively target most tumor cell types growing under normoxia as well as hypoxia..."  A good (if slightly out of date) overview of 2-dg http://onlinelibrary...02/iub.1251/pdf

 

A phase I dose-escalation trial of 2-deoxy-D-glucose alone or combined with docetaxel in patients with advanced solid tumors.

https://www.ncbi.nlm...ubmed/23228990\

 

Dual inhibition of Tumor Energy Pathway by 2-deoxy glucose and metformin Is Effective Against a Broad Spectrum of Preclinical Cancer Models

https://www.ncbi.nlm...les/PMC3237863/

 

Normalization of CD4+ T cell metabolism reverses lupus.

https://www.ncbi.nlm...pubmed/25673763

Drug/diet synergy for managing malignant astrocytoma in mice: 2-deoxy-D-glucose and the restricted ketogenic diet

https://nutritionand.../1743-7075-5-33

Synergistic effect of MEK inhibitor and metformin combination in low grade serous ovarian cancer.

https://www.ncbi.nlm...pubmed/28545687

 

Inhibition of glioblastoma tumorspheres by combined treatment with 2-deoxyglucose and metformin

https://academic.oup...edFrom=fulltext

 

Targeting cancer cell metabolism: the combination of metformin and 2-deoxyglucose induces p53-dependent apoptosis in prostate cancer cells.

https://www.ncbi.nlm...pubmed/20215500

 

Profiling and targeting of cellular bioenergetics: inhibition of pancreatic cancer cell proliferation

http://www.nature.co...jc2014272a.html

 

Caloric restriction and cancer: molecular mechanisms and clinical implications

http://www.nature.co...sis201546a.html

 

Modeling the Genetic Regulation of Cancer Metabolism: Interplay between Glycolysis and Oxidative Phosphorylation

http://cancerres.aac...77/7/1564.short

 


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#2 drtom

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Posted 18 September 2017 - 12:10 PM

Rhearon,

 

Thank you for posting your thoughts and the relevant references.

I think your logic is sound. The slow escalation of doses should allow you to feel any adverse effects and stop.

I am also 60 and have been taking metformin for 5 years (500 mg/day).

One question; how do you source 2gG?

 

Best,

 

DT



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#3 rhearon

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Posted 21 September 2017 - 04:28 PM

Hi DT

I have had good luck with the following supplier:

David Hong
RZ Everest Biotech, Co., Ltd.
Address: Ziyu Garden, Linyi Road, Rizhao City, Shandong Province, China.
Website: www.cneverest.com
Skype: rzeverest
Please update me if you try the 2DG. I highly recommend a blood glucose monitor - the only side effects up to 64mg/kg seems to be hypoglycemia. Sugar, obviously, cures this, but it's worth monitoring. FYI - A friend tried this combo for her lupus with remarkable results.






Also tagged with one or more of these keywords: 2-dg, ketosis, cancer, longevity, ampk, metformin, caloric restriction

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