Are statins the new cancer killers or is the claim overhyped rubbish?

By Gregory Stoloff

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‘Statins can slash your risk of dying from cancer by up to 50%’ was the excited claim being made in several papers last week.  Long-term statin critic Dr Malcolm Kendrick hit back in an irritated blog a few days later describing the claim as “overblown hype” and “complete rubbish”. 

As a devoted fan of Malcolm work, this left me in a quandary. On the one hand I knew his views on statins were backed up by forensic research, on the other hand my story about a pioneering cancer clinic in the Daily Mail last week had claimed that statins could help to treat cancer. 

The 50% claim originated in two research papers involving thousands of men and women presented at a big cancer conference in Chicago, which reported on studies tracking cancer incidence in patients who were or weren’t taking statins.

Malcolm’s strenuous objection was that not only were these observational studies – so you could only say there was a correlation not causation – but there was a built in bias – sicker people would be more likely to be on statins. What’s more, evidence from more reliable trials showed that it was people with high cholesterol had a lower risk of cancer.

A game changer in the world of cancer

The cancer clinic I’d written about for the Daily Mail is doing something radical and, it seemed to me, potentially game-changing in the way we treat cancer. The Care Oncology Clinic in Harley is treating cancer patients who have pretty well run out of options with a cocktail of four, old, off patent (and consequently very cheap) drugs, one of which is a statin.

It is the brain child of one-time City wiz kid Gregory Stoloff , who formed his own drug company a decade ago and begun searching the medical literature for off patent drugs that had evidence for effectiveness against cancer. He and his team identified hundreds and winnowed them down to the four in the cocktail. The others were an antibiotic, the diabetes drug metformin and a de-worming pill. (This is not a full account so do read the article and the post on this site that went with it).

There was widespread support for the critiques Malcolm and others had mounted, so had Stoloff got it badly wrong? Or were his critics, however informed about statins and their role in heart disease, simply ignorant about the remarkable impact they could have on cancer? Either way the issue seemed important. The best way to find out was to give him the space to put the case for statins as a cancer killer.

How statins slow cancer’s growth and damage its protective shield.

By Gregory Stoloff

The media reports about statins and cancer largely concentrated on the preventative side – could they cut your risk of cancer as well as of heart disease? I’m not so concerned about that. I think that if you are healthy, the benefits of cancer protection with statins don’t outweigh the risk of diabetes and the other known side-effects.

But if you are at raised risk of cancer from gene variations, or if you had cancer previously, then it might be worth it. You may be able to reduce the side effects by taking the statin considerably less often than the daily dose given against heart disease.

Dr Kendrick and others have strongly criticised the use of observational trials as evidence for statin’s effectiveness on the ground that they are misleading, can’t prove causation and are vulnerable to bias. What he seems to rely on are randomised controlled trials, which is odd as his research has uncovered the many ways these trials can be deliberately manipulated to give very misleading results.

Clinical trials are highly artificial experimental set ups that frequently involve younger and fitter patients than those who will actually get statins in the real world. Observational trials record real world activity but they are only a start. If they do show correlations the next step is to determine the mechanism that might be causing it. This is what has now been done for statins and cancer and it is these mechanisms that are important and not just the cholesterol lowering aspects of statins.

Statins’ three pronged attack on cancer

Statins have an impact on cancer cells via at least three different mechanisms. They attach themselves to pathways or proteins that are important for cancer growth, turning them on or off. One is HMG CoA, familiar as the pathway in the liver that packages up fats and cholesterol but it is also found in cancer cells. Another is PPAR Gamma, proteins that control a lot of cell activity including cell death (apoptosis), which is something cancers block. Finally they indirectly reduce the number of a type of receptor on the surface of cells called GLUT 1 that allows in glucose – the energy source for all cells.

Statins’ ability to slow down the action of HMG CoA has a damaging effect in cancer cells because this is the pathway they use to make the cell walls for all the new daughter cells that being are created at a furious rate. By blocking HMG CoA’s activity, statins slow down the rate at which the cancer multiplies and spreads.

As well as impacting on cancer cells’ supply of building materials, statins are able to reduce the energy available to them. They do this by increasing the levels of HDL production. In cancer cells the HDL increase leads to a reduction in the number of surface receptors – known as GLUT 1 – which pull glucose for energy out of the blood stream. Most cells use GLUT1receptors to do this but cancer cells have significantly more than normal cells and, because they are so much more glucose hungry, they are more sensitive to a reduction in numbers than normal cells. Again growth slows down

The third prong of statins’ attack, which involves turning on PPAR Gamma, delivers a double whammy to cancer. One of a cancer cells’ most important survival mechanisms is the ability to turn off a default program known as “apoptosis” that causes a cell to “commit suicide” when it is damaged or starts behaving erratically. Turning on PPAR Gamma activates apoptosis, and since cancer cells are more sensitive to it than normal cells, the cancer starts dying off.

Making a dent in cancer’s shield

PPAR Gamma also influences some immune cells that surround a cancer known as Tumour Associated Macrophages (TAMs). Surprisingly they aren’t there to attack the cancer but to defend it. Our immune system has the ability to both attack and defend cells and another of the tricks in cancer’s survival kit is being able to turn on this protection. Like cancer cells themselves, TAMs are also much more sensitive than healthy cells to PPAR Gamma’s ability to trigger apoptosis. This starts a process that, via a complex series of steps, ends in the macrophages’ suicide and a reduction in the cancer’s protection.

Interestingly the processes that statins target in cancer cells and in the surrounding TAMs are the same ones targeted by the new immunotherapy drugs that last week were being hailed as a breakthrough in treatment because survival times of some of the patients are considerably longer than usual.

Of course there are plenty of unknowns about the way that statins impact on cancer and if we had a rational system of developing new and effective treatments serious research would be underway to answer them. But the brutal truth is that our current research model is not based on science – this looks promising lets test it – but on profit – this old drug looks promising but unprofitable so we will ignore it.

It was in an attempt to find a way round that blockade that drove me to set up the clinic. Statins certainly have an effect on cancer and we know that they are far less damaging than the existing drugs with their massive price tags. So my idea was to try them on an off-label basis and monitor the results.

I believe that we will soon have good evidence for effectiveness and we already know the risks. But even when we present it I don’t believe that the big companies will pick up on it.

Instead I predict that we will see more small individual clinics springing up the exploit the potential of these older and very cheap drugs.

Gregory Stoloff

Gregory Stoloff

Gregory Stoloff is founder and CEO of the drug discovery company SEEK, which he set up in 2004 after a successful career in investment banking. Its aim was to focus on research into medical issues that involved the immune system. He has also been involved in several publications and holds numerous patents relating to immune system products. He is also the CEO of Care Oncology Clinic.
Gregory Stoloff

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  • Suppose that it is true that statins reduce the number of available GLUT1 receptors. Fine, less glucose going into cancer cells that way. Endothelial cells also rely on GLUT1, if I’m not mistaken.

    It has come to attention of many people that statins are not unlikely to raise blood glucose in a substantial number of people. Some publications indicate this may be partially due to inhibition of insulin secretion in ß-cells, e.g. [1]

    As far as I’ve read, statin-induced diabetes is usually similar to T2DM, the hallmark of which is high (or very high), but still insufficient insulin, or in other words: extreme insulin resistance.

    Now, everybody knows that insulin ramps up the number of GLUT4 transporters, especially in cells that for some reason don’t easily become insulin resistant, like fat-cells and probably cancer cells.

    So… where is the data on GLUT1 vs. GLUT4 transporters, which of them contributes most of the glucose transport, especially in the statinated & hyperinsulinemic patient?

    It is refreshing to see a metabolic approach to cancer treatment, but personally I’d prefer a method that does not potentially mess with or even fuck-up every single cell in the body.

    If the desired goal is to starve cancer cells of glucose, why not use a low-cal KETO diet, glucose analogues that can’t be metabolized… Prof. Seyfried has a lot to say about that, and I think it makes more sense.

    Normal cells will do just fine with only little glucose around, given the body is properly fat-adapted. Not all, but many cancers don’t seem to do well with low glucose and high ketones.

    My 2 cents.

    [1]: “Inhibition of Cholesterol Biosynthesis Impairs Insulin Secretion and Voltage-Gated Calcium Channel Function in Pancreatic ß-Cells”, F.Xia et al., 2008, doi: 10.1210/en.2008-0161

  • Robert!! I am absolutely with you on this one, so why take a drug to do something that changing diet alone can achieve?? Oh that’s because using a nice juicy drug gives nice juicy profits!! FYI try looking at Dr Dominic D’Agostino’s work on ketogenic diets and cancer – amazing!

  • Ketogenic diets work best with brain tumours but closely following that kind of diet is not realistic for the vast majprity of people. Stains in this setting are combined with the diabetes drug metformin along with an antibiotic and mebendazolre. I suggest you both read the other posts relating to this clinic to get a better view of the overall picture of how these drugs work in combination. This article focuses purely on the statin element. The statins are chosen for their effectiveness (some are more effective than others). I used Lovastatin which is off patent. There os no big profit for the pharmaceutical company any more.

  • Ketogenic diets work best with brain tumours but closely following that kind of diet is not realistic for the vast majprity of people. Statins in this setting are combined with the diabetes drug metformin along with an antibiotic and mebendazole. I suggest you both read the other posts relating to this clinic to get a better view of the overall picture of how these drugs work in combination. This article focuses purely on the statin element. The statins are chosen for their effectiveness (some are more effective than others). I used Lovastatin which is off patent. There is no big profit for the pharmaceutical company any more.

  • Jane, I’m wondering if you think “closely following [a ketogenic] diet is not realistic for the vast majority of people” because of the awful definition found on many sites such as the Mayo Clinic, and others focusing on its use to combat epilepsy.
    Because of the unjustified terror of saturated fats over many decades, the typical formulation of a “ketogenic diet” is lean meat or fish, minimal green vegetables, and gigantic quantities of vegetable oil. This, I entirely agree, would be totally unpalatable for “the vast majority of people”.

    I have been following low-carb for over six years now, and have been strictly ketogenic for over a year, which helped me overcome my oesophageal cancer with minimal treatment, avoiding the proposed surgery. I did not take a statin, and my oncologist refused to prescribe metformin.

    However, my ketogenic diet was like that described as “a well-formulated ketogenic diet” by Drs Jeff Volek and Stephen Phinney in their “The Art and Science of Low-Carbohydrate Living”.
    It is very easy to stick to a diet of fat meat, oily fish, eggs, cheese, cream and lashings of butter on minimal quantities of green vegetables. The odd bit of 90% cocoa butter chocolate provides more than enough in the way of desserts!

  • As usual it’s the drug companies trying to push a drug or 6 when eating the right kind of food would have the same effect!! Ketogenic diets are wonderful for helping all sorts of chronic and deadly diseases and although they may take a bit of willpower the food is delicious, varied and satisfying. It’s no more than telling an alcoholic he shouldn’t drink. Carbs can be addicting and some people need a detox period to get their cravings under control, and become fat-adapted, but once past that stage the diet is easy – it frees you from hunger and being food-focused all day long. I wouldn’t call it a diet in fact, it’s a way of eating, or a way of life. I’ve been low carb now since 2003, about 90% of my time. Would never change it, and all around me I’m watching my contemporaries fall by the wayside with some disease of the metabolic syndrome. (I’m 53). I would never recommend Statins to anyone – cholesterol tests (unless it’s a particle size check) tend to be meaningless, and if they do climb higher than a person’s normal level it’s an indicator that there is an underlying problem (usually inflammation – caused by – you guessed – carbohydrates) which needs to be addressed, and trying to lower the cholesterol is in fact stopping the body’s healing process. It’s like arresting the fireman at the scene of the fire – he didn’t cause the blaze – he is there to help!

  • Don’t get me wrong Archie, I am a big fan of ketogenic diets, I myself removed all grains, potatoes, alcohol and most definitely anything containing sugar in any of its many guises. Pleased to hear you have overcome esophogeal cancer with minimal intervention (were you also stage 4?). I am sure I was in nutritional ketosis myself but I had no way of testing back then and no-one had even coined the term ‘ketosis’ in 1999. I had a very slim chance of survival and throwing everything at it was what was needed. I used lovastatin in combination with berberine, a natural metformin equivalent. However I don’t believe most people have this willpower to radically alter their diets enough, I know this from experience. I have tried to help many others with advanced cancer without these drugs, telling them to cut right back on anything with a high glycaemic index and they have subsequently died because it was not enough. On its own the ketogenic diet only appears to work effectively in brain cancer. It is a tough gig. I’ve been there. I had a 3% chance of surviving 5 years (I am now 17 years post terminal diagnosis). Anything that can help assist the process of starving the cancer has to be a good thing, be it ketogenic diet, metformin, statins or berberine. And Big pharma is dead. Don’t worry about them. Worry about how to get well if you have cancer and stop being prejudiced against statins just because someone thinks you might possibly get a problem with your heart or diabetes a few years down the line. That’s why you combine statins with metformin or berberine. And there are studies looking into combining metformin and ketogenic diets now although this might be going too far! Combinations work far more effectively than one approach on its own. Dr Malcom Kendrick has written a blog admitting he might be entirely wrong about statin use for cancer. He is arrogantly ignoring the many trials which clearly show a benefit.

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