Can statins really increase cancer survival?

Statins, particularly lipophilic statins, may exert multiple anti-cancer benefits, including decreased tumour growth, decreased aggression, angiogenesis, and metastasis; a growing number of research studies have shown that they have an off-label role in increasing cancer survival.

Sugar feeds the primary cancer; fat spreads the cancer

In London, oncologists have been using statins off-label to fight cancer since 2005, but in 2012 a group of oncologists formed Care Oncology, which is now also in the USA, and developed a four-drug 'metabolic' protocol to increase patient survival by restricting the cancer's ability to feed and spread  They use the same four drugs on any and all cancers. Their aim was to target glycolysis, glucose and cholesterol and impact the whole cancer process. This is exactly what CANCERactive has been telling people with cancer, as a part of its Active8 programme for nearly twenty years!

How to starve cancer

Cancer may use glucose to grow but it uses fat to spread.  Research shows that cancer burns sugar in the primary tumour but switches to burning fatty acids once it arrives in the adjacent lymph system. Furthermore, other research shows cancer cells 'load up' with lipids to begin their travels around the body and a third study shows that people with the highest levels of blood fats (cholesterol and triglycerides) develop more metastases and survive least. A number of cancers are worsened by high blood fat levels (for example lung and prostate cancer); and there is research with a number of cancers (for example, breast and lung cancer) where a low fat diet increases survival.

Statins, or HNG-CoA reductase inhibitors, reduce serum cholesterol and the risk of heart attack and stroke.  Early observational studies suggested that people who were taking statins had less colorectal and skin cancer. 

In 2021, researchers from Brisbane, Australia, conducted a Nationwide study and showed that women (aged 18-89) who were already using statins had a 4-year increased survival over non-users for breast, colorectal cancer and melanoma. Lipophilic statins, rather than hydrophilic statins, produced the better results (7).

Lipohilic vs Hydrophilic statins and cancer

Consistently throughout the research, the best results are obtained when using lipophilic statins (Atorvastatin, Lovastatin, Fluvastatin, Pitavastatin and Simvastatin, for example) rather than hydrophilic ones (Rosuvastatin, Pravastatin, as the former not work only in the blood stream; they work in the tissues, because they can cross membranes and enter cells.

Atorvastatin in the USA is called Lipitor.

Statins may have several actions in cancer therapy

Much of the research is quite old and from the laboratory - 

1. Cholesterol is a major part of cell membrane structure and mevalonate produced in membrane synthesis is a precursor of dolichol which stimulates DNA synthesis and several cancer proteins. Mevalonate is also a precursor to GPP and FPP which regulate the ras and rho genes, which can cause cells to grow wildly. Ras and rho are involved in many cancers and statins like lovastatin and cerivastatin have been shown to block these genes (1)
2. The mevalonate pathway promotes YAP/TAZ activity, while statins block the pathway, impair YAP/TAZ activityand inhibit the development of cancer cells (10). 
3. Statins also seem to increase apoptosis (cancer cell death) in cell lines from brain tumours, mesothelioma and cervical cancer.
4. Statins reduce prenylation (lipidation) - the attachment of hydrophobic molecules to proteins - and therefore signaling in tumour progression.However, statins have actions other than those produced by lowering cholesterol
5. Statins reduce cytokines, and thus inflammation and metastasis (6).
6. Kodach et al. found that statins act as DNA methyltransferase (DNMT) inhibitors,  inducing differentiation of colorectal cancer (CRC) cells, and reducing “stemness” (9).

Indeed a team from North Western in Chicago asked "Can we translate preclinical and epidemiologic data into clinical benefit?" Young Wang Chae and his team stated, "Statins have been investigated for a variety of cancers, early and late stage, and in combination with chemo and radiotherapy. So far promising results have been reported with statin use in pediatric brainstem tumours, early stage breast cancer, hepatocellular cancer (HCC), colorectal cancer, refractory or relapsed Multiple Myeloma, and refractory acute myeloid leukemia (AML)" (11).

While there's a lot of inference, we still lack the big Clinical Trial data.

Which cancer patients may see increased survival by taking a lipophilic statin?

Prostate cancer is well understood to be driven by higher blood fat levels - 

1. In a 2019 study from Queen's University Belfast, while statins had no effect on reducing prostate cancer risk, the researchers found that cholesterol-lowering statins could reduce aggressive and fatal prostate cancer once a man had prostate cancer, by 24%. 

2. In a 2020 prostate cancer study, this time from Sidney Kimmel Cancer Center in Philadelphia, 13,000 'high risk' men who had a Gleason score of over 8, were followed and those who took a statin along with metformin, had a median survival of 3.9 years, statins alone was 3.6 years, and metformin alone was 3.1 years, no higher than taking neither at 3.1 years.

3. One study by Dr. Lauren Christine Harshman an assistant professor at both Dana-Faber and Harvard Medical School suggests that taking statins can slow down the rate of progression in prostate cancer where men are also taking hormone therapy (ADT). As we said above, prostate cancer progression is known to be linked to blood fat levels and natural Lycopene has similar results.

Colorectal cancer

1. Patients where 40 mg Simvastatin was added to FOLFIRI showed longer survival times than previous studies.
2. Patients with a KRAS mutation who added 80 mg of simvastatin to cetuximab and irinotecan exhibited longer survival times.
3. A 2013 overview (Lockhead, Chan) stated that statins could modulate cancer cell growth, apoptosis and inflammation.
4.  Statin use is linked with a lower risk of colorectal cancer.

Breast Cancer

1. There is mixed research on statins with breast cancer. One Swedish study sought to clear this up and found that both pre-diagnostic statin use and post-diagnostic statin use was linked to lower levels of breast cancer-related death.
2. A 2017 review suggested early stage breast cancer use of lipophilic statins was linked to a greater 5 year survival. In another study on 10-year survival, the use of lipophilic statins was linked to a 10% increased survival. No such benefits occurred with hydrophilic statins. This review did warn that long term usage might have a negative effect on risk and survival.

Ovarian cancer and endometrial cancer

1. In a June 2020 study presented at the American Association for Cancer Research online conference, use of a statin was associated with a 40% lowered mortality in ovarian cancer. Where the statin was lipophilic, the figure rose to 43%. The biggest benefits came with patients who had High Grade Serous or Endometriod cancer.

Lung cancer

1. A  2015 review concluded, in patients with lung cancer, there was evidence that people taking a statin, particularly simvastatin, had reduced mortality. This also seems to be true for those people taking the statin before diagnosis.
2. In a March 2019 meta-analysis of observational studies on statins with 98,000 lung cancer patients, statins were believed to show significant survival benefits, especially when given after diagnosis. This was particularly significant with grade 4 stage 4 patients. 

Kidney cancer

      1. Early studies on statins with kidney cancer showed mixed results (possibly because of the type of statin used), so a 2017 meta-analysis set out to find the truth.  Across 12 studies and more than 18,000 patients, statins were noted to significantly improve the survival outcomes in kidney cancer.

Atorvastatin plus metformin

1. There also seems to be more evidence for the simultaneous use of both metformin and a statin. One study showed that they synergistically inhibited endometrial cancer growth. Another showed that they reduced recurrence of prostate cancer in type-2 diabetes patients. The statin here was Simvastatin.

Statins - warnings?

1. There is mixed research on angiogenesis. Some studies suggest statins reduce this; others suggest promotion of blood supplies in a review of statins and cancer in the Oncologist (2).
2. There are strong arguments that statins can actually increase cancer risk due to modifying the immune response (3) and increasing the production of liver enzymes.
3. And there is research showing an increased risk of cancer in the elderly when taking atorvastatin (4), and in people with a history of breast and prostate cancer (5).
4. Osteoporosis A 2021 Study supports the claims that bone mineral density decreases with an increase in a statin dose. Hydrophilic statins, like pravastatin, had a better metabolic profile in the lumbar spine than the lipophilic statins. Obviously, if you are on Letrozole, anastrozole and/or bisphosphonates, this might be a concern (12).
5. Liver Enzymes The Mayo Clinic state that, occasionally, statin use may cause an increase in the level of enzymes that signal liver inflammation. This would obviously be a problem to cancer patients who already have liver issues. "Contact your doctor immediately if you have unusual fatigue or weakness, loss of appetite, pain in your upper abdomen, dark-colored urine, or yellowing of your skin or eyes".
6. CoQ10 and Dementia. Low CoQ10 levels are a risk factor for chronic illnesses such as cancer and Dementia. Lowered CoQ10 levels in women with breast cancer has been linked to more cancer advancement. See CoQ10. Again, the Mayo Clinic suggests that people taking statins should supplement with CoQ10 100-200 mg. So do we.

Conclusions on statins for cancer patients

Some cancers - for example, Prostate and Lung cancer, are known to have strong links between blood fat and metastases. In other cancers, for example colorectal cancer and breast cancer, the research is at beast adequate with the strongest study being the Brisbane study.

With brain cancer, the way cancers spread is very different. However, there are a number of studies showing a lipophilic statin increases brain cancer survival because it extends the effectiveness and life of the main drug Temozolomide,TMZ, suppresses cell growth, migration, metastasis, inflammation, angiogenesis, and promotes apoptosis. 

But it is really hard work to find anything that even resembled a real clinical trial on the Internet including using Care Oncology's own references. Test tubes aren't believed on vitamin effects; should we believe them here, especially with an industry - the Statin manufacturers - that will spin anything to make their drug look good? However, in truth, if you have a healthy liver and cholesterol levels over 5.0, and if your cancer is stage 3 or 4, what have you got to lose?

Ironically, Care Oncology and others use statins alongside Metformin, which aims to cut blood glucose. Research shows statins can increase blood glucose levels by 27 per cent and diabetes risk by 10-15 per cent according to the US Diabetes Association; Atorvastatin being the worst.

The Bottom Line - Taking a statin to fight cancer

Statins cut blood fat; and that's a good start if you have cholesterol over 5.0. But, apart from the proven fat cutting, it is really hard work to find anything that even resembled a real clinical trial on the Internet even using Care Oncology's own references. Test tubes aren't believed on vitamin effects; why should we believe them here, especially with an industry - the Statin manufacturers - that have been notorious for spin to make their drug look good? 

However, in truth, if you have no liver issues and cholesterol levels over 5.0, and if your cancer is stage 3 or 4, what have you got to lose?

Go to: Statins, Diabetes and Alzheimer's

Go to: Statins link to Atherosclerosis and Heart failure

Natural alternative - Lycopene

Cancer patients reading this might also look at the bioactive compound lycopene.  Lycopene from tomatoes and watermelon is known to reduce prostate cancer risk, and aggressive and fatal prostate cancer too. It attacks pathogens such as E. coli. This antioxidant also blocks glutaminase - the enzyme that converts glutamine to glutamate (a fuel for cancer cells) - and attacks cancer stem cells, and 25 mg of lycopene beat statins in research. Lycopene is also a strong antioxidant but a search on the Internet showed no contraindication with drugs. It also reduces Lipoprotein A, which is the dangerous form of LDL. 

To fight cancer we use 25-60 mg of lycopene a day, taken with olive oil and black pepper. We also use natural Plant Sterols and C-Stain, a natural compound shown to stop angiogenesis and cell division. No evidence of liver issues or dementia has been shown.

Go to: Is Lycopene better than statins?

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References

1. Soma MR, Corsini A, Paoletti R. Cholesterol and mevalonic acid modulation in cell metabolism and multiplication. Toxicol Lett 1992;64–65: Spec No1–15.
2. http://theoncologist.alphamedpress.org/content/11/3/306.full#ref-48
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2365486/
4. Ann Intern Med. 2007 Jul 3;147(1):1-9.
5. N Engl J Med. 2007 Oct 11;357(15):1477-86.
6. Landskron G, De la Fuente M, Thuwajit P, et al. Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res. 2014;2014:1–19.
7. Australian Study - https://www.canceractive.com/article/lipophilic-statins%20extend%20survival%20in%20cancer%20patients
8. Effects of statins on brain tumors: a review; Amir R Afshari, Hamid Mollazadeh, Neil C Henney, Tannaz Jamialahmad, Amirhossein Sahebkar; Semin Canc Biol; 2021 Aug;73:116-133
9. Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell ‘stemness’ via the bone morphogenetic protein pathway; Kodach LL, Jacobs RJ, Voorneveld PW, Wildenberg ME, Verspaget HW, van Wezel T, Morreau H, Hommes DW, Peppelenbosch MP, van den Brink GR, et al. Gut. 2011;60(11):1544–1553.
10. Metabolic control of YAP and TAZ by the mevalonate pathway; Sorrentino G, Ruggeri N, Specchia V, Cordenonsi M, Mano M, Dupont S, Manfrin A, Ingallina E, Sommaggio R, Piazza S, et al. Nat Cell Biol. 2014;16(4):357–366. doi: 10.1038/ncb2936.
11. Statins as anti-cancer therapy; Can we translate preclinical and epidemiologic data into clinical benefit? Young Kwang Chae et al.  Disc Med; 2015 Dec;20(112):413-27.
12. Diagnosis of osteoporosis in statin-treated patients is dose-dependent; Annals of Rheumatic Diseases; Michael Leutner et al; BMJ