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Advanced Prostate Cancer
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Metformin and Berberine

Hi All...I'm learning a lot from your previous posts. Thank you! Thus far, Metformin and/or Berberine seem to be worthy of further consideration. Although there does not appear to be convincing scientific evidence of their effectiveness for PCa patients (absent diabetes), both your reported experience and the low cost suggest at least a trial use.

Like others, my MO quickly dismissed Metformin with "metformin has been and is being studied as an anti-cancer treatment but is not proven and is not standard of care or something I would recommend at this time" -- even though I argued that I've long been "pre-diabetic" with fasting glucose consistently around 100 (95-105) for years despite multiple glucose control supplements and a low carb diet. How have others managed to work around their unsupportive MO and does doing so sound reasonable with or without ADT?

Berberine, as a natural alternative, sounds appealing. What dosages and brands have others found helpful? And any sense of the relative effectiveness compared to Metformin?

16 Replies
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Metformin is sort of a no brainer. It is cheap, and is good on many levels, even if you don't have prostate cancer.

The same for Trental.

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There are many mos who will never step out of the box even with clinica data and many who will. Till they find a definate cure for this disease, its your right to find someone who will. Good luck. Rocco

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Like you, my MO refused Metformin. My primary care physician prescribed it as I was pre diabetic.

Regards,

Gary

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Same here Gary. I showed my GP the evidence and she wrote me a script.

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My situation is the as Garythomas. I am pre-diabetic, too. I brought the Metformin issue up to my Mayo MO 2 years ago. He conceded that there may be some benefit in using Metformin, but it is “controversial,” (his favorite saying when I bring up complementary or adjunct treatments to the standard protocol). He said he couldn’t prescribe it for me solely on the basis of my PCa, but maybe my family doctor could based on my pre-diabetic condition. So, I went to my family doctor and discussed it with him. I have been on Metformin in addition to ADT for 2 years now. Hopefully, it is helping the ADT work better and longer, and it has definitely helped lower my glucose and A1c levels.

Mark

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I've tried Metformin twice and had to stop because of bad side effects. Like Bill, I'd be interested to hear what experience folks have had with berberine.

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These studies may give you more comfort with the idea of investing in some berberine supplements. I have been taking berberine before every meal for the last 18 mos with no SEs. My A1c has fallen significantly, a payoff in itself that justifies my investment as I was creeping into the pre-diabetic range.

ncbi.nlm.nih.gov/pubmed/296...

ncbi.nlm.nih.gov/pubmed/291...

ncbi.nlm.nih.gov/pubmed/290...

ncbi.nlm.nih.gov/pubmed/266...

And there is much more research on berberine. Also, "...Curcumin, resveratrol, apigenin, anthocyans, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways" From ncbi.nlm.nih.gov/pubmed/268...

I use the Solaray brand of Berberine, 2 capsules with each meal. As for the urologists, the first one in AZ learned about my taking IP6 8 mos. after I had started. In my second month I met, he read my PSA and was startled. I said nothing because at dx he told me supplements don't work. The 0.1 caused him (third year past dx) to request a DRE. He seemed startled again by the lack of nodules and he commented on it. I waited six months before explaining. My urologist here knows about my supplements and says little. I have a new MO (my first) in Brandon, FL. He read my list of supplements and didn't say anything. He undoubtedly heard from my urologist about the IP6 and all the other supplements as they are buddies.

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No brainer to take Metformin even if there is no proof it helps cancer. Very cheap and keeps your sugar down when it spikes with cancer meds. Sugar spikes can happen with statins and some hormone drugs. High sugar is not good for your health at all. My sugar was high.

My primary Chemo oncologist would not prescribe it. He does not prescribe anything off label. That is why I have 4 oncologists (UC Davis, Stanford, and 1 doctor I retained from City of Hope West Covina.) Had to get it from my family doctor who is cool about writing most prescriptions when others wont. Extended Release "XR" is better than the regular pill.

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Bill,

Life Extension [LEF] has long argued that 100 mg/dL is not a safe place to be for fasting glucose [1]:

"... we now know that the optimal fasting glucose ranges are 70-85 mg/dL based upon the totality of the scientific evidence.

"Those with glucose above 85 mg/dL are at increased risk of heart attack. This was shown in a study of nearly 2,000 men where fasting blood glucose levels were measured over a 22-year period. The startling results showed that men with fasting glucose over 85 (mg/dL) had a 40% increased risk of death from cardiovascular disease."

From a PCa perspective, it isn't glucose as such that has a proliferative effect, but the resultant loss of insulin sensitivity that leads to elevated levels (before the beta cells begin to fail.)

Many men at PCa diagnosis are pre-diabetic. Most will not become diabetic - but neither will they be treated by their GPs. This is a problem after PCa diagnosis IMO.

In the LEF article, Metformin is mentioned:

"Why Most Aging People Should Take Metformin.

"Metformin is a drug approved to treat type 2 diabetes. It is also very effective for those at high risk of developing diabetes due to elevated blood sugar readings. The Diabetes Prevention Program showed that metformin can reduce the risk of developing diabetes in high risk patients by a whopping 31%, with the greatest benefit for those significantly overweight.

"Metformin improves insulin sensitivity, and inhibits the release of glycogen (the storage form for glucose) from the liver, thus lowering fasting glucose blood levels.

"Life Extension funded research showing that metformin may have calorie restriction mimetic properties in laboratory mice. The drug’s unique ability to reduce glucose-insulin blood levels and its super low-cost make it something you’ll want to ask your doctor about."

Good luck with that!

Metformin is an AMPK activator. Because of the high number of LEF members who were denied a Metformin prescription, LEF offered this product as an alternative: [2].

...

The PCa Metformin intervention study that finally convinced Dr. Myers: [3].

-Patrick

[1] lifeextension.com/Magazine/...

[2] lifeextension.com/Search#q=...[Products]

[3] ncbi.nlm.nih.gov/pubmed/244...

Eur Urol. 2014 Sep;66(3):468-74. doi: 10.1016/j.eururo.2013.12.057. Epub 2014 Jan 4.

Metformin in chemotherapy-naive castration-resistant prostate cancer: a multicenter phase 2 trial (SAKK 08/09).

Rothermundt C1, Hayoz S2, Templeton AJ3, Winterhalder R4, Strebel RT5, Bärtschi D2, Pollak M6, Lui L6, Endt K7, Schiess R7, Rüschoff JH8, Cathomas R5, Gillessen S9.

Author information

1

Cantonal Hospital St. Gallen, St. Gallen, Switzerland. Electronic address: christian.rothermundt@kssg.ch.

2

SAKK Coordinating Center Bern, Bern, Switzerland.

3

Cantonal Hospital St. Gallen, St. Gallen, Switzerland; SAKK Coordinating Center Bern, Bern, Switzerland.

4

Cantonal Hospital Lucerne, Lucerne, Switzerland.

5

Cantonal Hospital Chur, Chur, Switzerland.

6

Lady Davis Institute for Medical Research Jewish General Hospital Montréal, Montréal, Canada.

7

ProteoMediX, Schlieren, Switzerland.

8

Institute of Surgical Pathology University Hospital Zurich, Zurich, Switzerland.

9

Cantonal Hospital St. Gallen, St. Gallen, Switzerland.

Abstract

BACKGROUND:

There is evidence linking metformin to improved prostate cancer (PCa)-related outcomes.

OBJECTIVE:

To evaluate treatment with metformin in patients with castration-resistant PCa (CRPC) and the effect of the treatment on progression-free survival (PFS) and PSA doubling time (PSA DT).

DESIGN, SETTING, AND PARTICIPANTS:

Forty-four men with progressive metastatic CRPC from 10 Swiss centers were included in this single-arm phase 2 trial between December 2010 and December 2011.

INTERVENTION:

Patients received metformin 1000 mg twice daily until disease progression.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

The primary end point was the absence of disease progression at 12 wk. Simon two-stage optimal design was applied. With a 5% significance level and 90% power, 44 patients were required to test PFS at 12 wk ≤ 15% (H0) compared with ≥ 35% (H1).

RESULTS AND LIMITATIONS:

Thirty-six percent of patients were progression-free at 12 wk, 9.1% were progression-free at 24 wk, and in two patients a confirmed ≥ 50% prostate-specific antigen (PSA) decline was demonstrated. In 23 patients (52.3%) we observed a prolongation of PSA DT after starting metformin. The homeostatic model assessment index fell by 26% from baseline to 12 wk, indicating an improvement in insulin sensitivity. There was a significant change in insulin-like growth factor-1 and insulin-like growth factor binding protein 3 from baseline to 12 wk. Sample size and lack of a control arm are the limitations of this trial; analyses are therefore exploratory.

CONCLUSIONS:

Treatment with metformin is safe in nondiabetic patients, and it yields objective PSA responses and may induce disease stabilization. The activity of metformin in PCa, along with its low cost, favorable toxicity profile, and positive effect on metabolic parameters, suggests that further investigation of metformin as therapy for patients with PCa is of interest.

PATIENT SUMMARY:

In this trial we assessed the use of the diabetes mellitus drug metformin in patients with advanced prostate cancer. We found disease stabilization and prolongation of prostate-specific antigen doubling time in some patients as well as effects on metabolic parameters.

TRIAL REGISTRATION:

This study is registered with ClinicalTrials.gov with the identifier NCT01243385.

PREVIOUS PRESENTATION:

The study was presented at ESMO 2012 (abstract 1460).

Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

KEYWORDS:

Castration-resistant prostate cancer; Metabolic parameters; Metformin

Comment in

Metformin for castrate-resistant prostate cancer: learning more about an old dog's new tricks. [Eur Urol. 2014]

PMID: 24412228 DOI: 10.1016/j.eururo.2013.12.057

[Indexed for MEDLINE]

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Thanks to all for your helpful insights and experiences. I've reviewed the excellent references suggested by Patrick and CalBear and will start Berberine immediately, followed by my annual GP visit. Should he also be reluctant to prescribe Metformin despite the research evidence, I'll turn to my skiing buddy who happens to be a physician and has helped me with scripts in the past.

Bill

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I was in a similar position with my MO. She would not prescribe Metformin. I ended up taking the research papers to my GP and he agreed to prescribe it.

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snoraste, are the research papers the one posted above? If not could you post and I'll try you technique with my urologist

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this is a piece that Patrick posted two months ago with a link:

healthunlocked.com/advanced...

If you search "metformin" here on this website there's plenty more

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I just told my husbands Family doctor I wanted him on Metformin and showed him the supportive info and that we follow Snuffy Myers info. He had no problem adding it to my husbands lists of meds and that the ADT wi also cause diabetes he was all for it.

When we went to MSk in New York his oncologist said ok.

But he can’t prescribe it.

I told him

Well his family Dr listened to him..

Good luck

Stephanie

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It's very odd to me that there is so much pushback on prescribing Metformin. Maybe becoming a diabetic was lucky for me (I certainly didn't think so at the time!), as I was already on maximum Metformin (1g 2x daily) before being diagnosed with a Gleason 9 PCa. However, I'm in my 12th year of battling this disease now, and if I'd have believed nomographs, I'd have passed 7 years ago...and I'm still hormone naive (sensitive), even after 4 years of continuous ADT in a clinical trial...I personally believe that it's been a big help to me, and I never had to push my MO about it, although he knows my thoughts about it, and I kinda believe he shares them too...you can read the study that Patrick noted above that shows there is benefit to its use - I have to believe it is one of the reasons I've been able to keep mine in control for as long as I have.

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Don’t listen to him.....take it. My MO (both of them) were totally against my taking .5 mg of DES as well as Metformin. 4 years later he is totally amazed and tells me that if someone walked in his office and wanted to do the same protocol he would tell them to “go for it”

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