Studies of single drugs, supplements or foods often have limited or poor results.
Synergy is an important factor not to be discounted. Those living in the "Blue Zones" that enjoy spectacular health and longevity do so because of lifestyle and diet. It is becoming recognized and accepted that synergy among drugs and supplements increases their effectiveness. A study on the synergy between two drugs that can help those with prostate cancer is below --the poor mice!
Metformin in combination with atorvastatin had stronger effects on growth inhibition and apoptosis in PC-3 cells than either drug alone. The combination also potently inhibited cell migration and the formation of tumorspheres.
Author: Zhen-Shi Wang, Hua-Rong Huang, Lan-Yue Zhang, Seungkee Kim, Yan He, Dong-Li Li, Chelsea Farischon, K...
Cited by: 18
Publish Year: 2017
Mechanistic Study of Inhibitory Effects of Metformin and Atorvast…
Figure it out. 5 mg/ kg. for 220 lb man.(100 kg) . only need 500 mgX3/week (1500 mg per week) and 80 mg/ kg for 220 lb man. (100 kg) . Only need 8000 mg x 3 per week. (24,000 mg per week). I get 140 mg atorvastatin an week and take about 1200 mg aspirin per week. Could I have done the math right?? Way more dose than a human could survive. Maybe I do need to take 10 to 20 times as many pills.
Like many cancer cells, prostate cancer cells need to take up and use large amounts of energy to grow, divide, and survive. To cope with this increased demand in energy, they have developed special metabolic processes which are vulnerable to targeting by some medications, including statins (which can reduce levels of blood cholesterol and other fats) and metformin (a diabetes drug which can help control blood sugar levels)(Ferro et al., 2019).
In addition, metformin and statins can also help manage obesity and metabolic syndromes (i.e. diabetes, high blood pressure, increased weight and high levels of blood cholesterol etc.) which are associated with increased risk and worse outcomes for prostate cancer (Gacci et al., 2017; Jamnagerwalla et al., 2018; Liss et al., 2019; McGrowder et al., 2012).
Laboratory studies show that both statins and metformin can act directly to reduce the growth and survival of prostate cancer cells, by targeting numerous molecular process both in and surrounding prostate cancer cells. This also has the effect of weakening the cancer cell – making it more vulnerable to standard therapies (Alfaqih et al., 2017; Vallianou et al., 2014; Whitburn et al., 2017; Zaidi et al., 2019).
Metformin may also be particularly efficient at targeting prostate cancer stem cells (a particularly resilient type of cancer cell), making them more sensitive to standard treatments like chemotherapy and radiotherapy (Iliopoulos et al., 2011; Mayer et al., 2015). In studies using mouse models of prostate cancer and other cancers, metformin decreased the dose of chemotherapy required to shrink tumours, and also helped to prevent relapse when given in combination with the standard treatment (Iliopoulos et al., 2011).
Diagram of cell breaking down each part's capabilities
A ‘dual effect’ targeting prostate cancer cells
There is also evidence that metformin and statins in combination can produce a ‘dual effect’ against cancer. In cell and animal studies, statin plus metformin together were able to directly kill aggressive prostate cancer cells, and reduce tumour growth and spread with a stronger effect than either medication alone (Babcook et al., 2014a, 2014b; Wang et al., 2017). This finding is also supported by a number of observational studies. One such study reviewed the outcomes for over 700 men with diabetes who underwent surgical treatment for prostate cancer. Their data suggested that patients who had taken both metformin and statins seemed to have a lower risk of their cancer returning following surgery (as indicated by biochemical markers) than those men who did not take these medications, or who took just one or the other medication (Danzig et al., 2015).
Two other observational studies (recently published in conference reports) analysed the clinical records of thousands of patients who had high-risk (i.e. more aggressive) prostate cancer, and found that patients who used of a combination of statins and metformin were less likely to die of prostate cancer during the study, compared to patients who did not take either drug. This effect was even more pronounced for patients with metabolic syndromes (Lu-Yao et al., 2015, 2018). Interestingly, one of the studies linked some brands of statins to better outcomes than others – with atorvastatin (i.e. the brand used in the COC Protocol) being the most effective (Lu-Yao et al., 2018).
Many observational studies have also singularly linked statin use or metformin use alone with improved outcomes in prostate cancer, including benefits in survival, and lower risk of relapse or progression to more advanced cancer, and better response to standard treatments (Alfaqih et al., 2017; Bonovas et al., 2008; Coyle et al., 2016; He et al., 2019; Hutchinson and Marignol, 2017; Murtola et al., 2017; Zhong et al., 2015).
Observational studies can at best only give a general snapshot indication of what is really going on, and some studies have not found any benefit of these medications for prostate cancer. Nevertheless, the positive findings from observational and mechanistic studies have been sufficient to initiate small and early-stage clinical trials in this area (Alfaqih et al., 2017; Whitburn et al., 2017).
Clinical studies show promise
Clinical studies have generally found that men who take statins or metformin may have decreased levels of prostate-specific antigen (PSA a molecular marker for prostate cancer risk and aggressiveness) (Khosropanah et al., 2011; Mener, 2010; Rothermundt et al., 2014).
A small pilot study in men with prostate cancer who were about to undergo surgery to treat the disease found that metformin for up to 1.5 months prior to surgery appeared to reduce markers of cancer cell division, and a trend towards decreased PSA was also noted (Joshua et al., 2014). A different randomised study in newly diagnosed men with prostate cancer reported that atorvastatin use for at least 28 days prior to surgery also appeared to reduce markers of cancer cell growth and division (Murtola et al., 2018), compared to placebo.
In another small exploratory study, some patients with aggressive prostate cancer who took metformin also had decreased PSA levels, and metformin also appeared to help stabilise disease progression for some of these patients (Rothermundt et al., 2014). PSA decreases were also seen in a small Phase 1 study investigating metformin in combination with another treatment in men with aggressive and previously treated prostate cancer (Parikh et al., 2019). And in a related trial, metformin alongside exercise was also shown to help counteract potential increased cardiovascular and metabolic problems which has been linked to androgen-deprivation therapy – a standard treatment option for men with some types of prostate cancer (Nobes et al., 2012).
The results of the above studies are promising; however, one weakness is that few had comparison control groups. In contrast, a fully randomized controlled trial in patients with very advanced prostate cancer which investigated metformin alongside their usual chemotherapy regime found that although metformin was well tolerated, no significant clinical benefit was noted in these patients (Martin-Castillo et al., 2018). A different study, also in men with heavily advanced prostate cancer also found no real benefit of adding metformin to standard therapy (Mark et al., 2019). These results show that more studies are still need, to help refine exactly how and when metformin and statin use may have most benefit against prostate cancer. Larger randomised controlled trials are ongoing and will help to further establish the evidence (Crawley et al., 2017).B
Thank you! You might find the ScienceDaily link in my reply to Graham49 interesting. Synergy of nutrients is a basic fact. Scurvy being cured by vitamin C is an example of how long the knowledge of a balanced diet, the synergy between foods, to provide health and longevity has been known. Yet many still look for just ONE substance, ONE drug, ONE supplement, ONE treatment to combat the enemy, cancer, and win the battle or at least come to a stalemate. Much like having an army without an air force, navy or specialized units--or--a boxer that only has a jab against an opponent that fights with combinations.
Yes that SD article is great. When I think how these and other agents that take out p53 mutations it remindsMe of the P53 Mustang - a warbird to take them out.
BTW metformin is a sirtuin and epigenetic regulator that does MUCH more than just regulating sugar metabolism. With the right synergies I think it may be a super drug for health.
Metformin has and is being studied with positive results to promote longevity and health. AMPK!
Thanks for the video. I lived within a few miles of the US Naval Station at Quonset Point when in my age was in the single digits. Occasionally the pilots, training, would break the sound barrier rattling some windows! The neighborhood considered these men to be heroes ready to defend the country. Today---uhh--I imagine complaints would be filed!
Jan 24, 2017 · Tomoo Iwakuma, M.D., Ph.D., an associate professor in the Department of Cancer Biology, and his team have published the first research showing how the use of statins, such as Lipitor (atorvastatin …
Thnks for the article. I could not find any dosage for metamorfin and statins, what would be the theraphy? Is it once a day one pill of statin and one of the metamorfin, or what means "high dose" for high dose of cholesterol?
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Green tea extract and Advil
How many of you are taking melatonin and how many of you are taking metformin?
Current Consensus on Metformin and Berberine?
