Statins

Safety and precautions

Cancer risk or outcomes

Risk of cancer as a whole

Pravastatin is linked to an increasing risk of cancer as a whole with increasing age.¹Bonovas S, Sitaras NM. Does pravastatin promote cancer in elderly patients? A meta-analysis. Canadian Medical Association Journal. 2007 Feb 27;176(5):649-54. However, risk of cancer as a whole has not been linked to statins as a whole.²Browning DR, Martin RM. Statins and risk of cancer: a systematic review and metaanalysis. International Journal of Cancer. 2007 Feb 15;120(4):833-43; Bjerre LM, LeLorier J. Do statins cause cancer? A meta-analysis of large randomized clinical trials. American Journal of Medicine. 2001 Jun 15;110(9):716-23.

Bladder cancer

People treated with statins have shown slightly higher risk of bladder cancer³Vinogradova Y, Coupland C, Hippisley-Cox J. Exposure to statins and risk of common cancers: a series of nested case-control studies. BMC Cancer. 2011 Sep 26;11:409. as well as more aggressive bladder cancer and higher incidence of radical cystectomy.⁴Hoffmann P, Roumeguère T, Schulman C, van Velthoven R. Use of statins and outcome of BCG treatment for bladder cancer. New England Journal of Medicine. 2006 Dec 21;355(25):2705-7.

Breast cancer

Statins are possibly linked to higher risk of breast cancer, especially among elderly people.⁵Bonovas S, Lytras T, Sitaras NM. Statin use and breast cancer: do we need more evidence and what should this be? Expert Opinion on Drug Safety. 2014 Mar;13(3):271-5. People treated with statins (predominantly lipophilic statins) for 10 years or longer experienced 83% higher risk of invasive ductal carcinoma and 97% higher risk of invasive lobular carcinoma, but no evidence of increased risk with use for less than 10 years.⁶McDougall JA, Malone KE et al. Long-term statin use and risk of ductal and lobular breast cancer among women 55 to 74 years of age. Cancer Epidemiology, Biomarkers & Prevention. 2013 Sep;22(9):1529-37. A separate large study of more than 2 million people from the UK also found no increased risk of breast cancer from statin use.⁷Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010 May 20;340:c2197. Also see evidence of lower risk of breast cancer in How can statins help you? What the research says ›

Colorectal cancer

People treated with statins, especially atorvastatin, have shown a higher risk of colorectal cancer in some studies⁸Fujimoto M, Higuchi T, Hosomi K, Takada M. Association between statin use and cancer: data mining of a spontaneous reporting database and a claims database. International Journal of Medical Sciences. 2015 Jan 22;12(3):223-33. although the increased risk was slight when adjusted for the presence of colitis and Crohn’s disease in one analysis.⁹Vinogradova Y, Coupland C, Hippisley-Cox J. Exposure to statins and risk of common cancers: a series of nested case-control studies. BMC Cancer. 2011 Sep 26;11:409. Another study found a higher incidence of rectal cancer compared to colorectal cancer as a whole among statin users also treated with glucose-lowering drugs.¹⁰Zanders MM, van Herk-Sukel MP et al. Are metformin, statin and aspirin use still associated with overall mortality among colorectal cancer patients with diabetes if adjusted for one another? British Journal of Cancer. 2015 Jul 28;113(3):403-10. No increased risk from use of statins was found in other studies.¹¹Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010 May 20;340:c2197; Renman D, Lundberg E, Gunnarsson U, Strigård K. Statin consumption as a risk factor for developing colorectal cancer: a retrospective case study. World Journal of Surgical Oncology. 2017 Dec 16;15(1):222. 

Lung cancer

People with wild-type p53 lung cancer (lung adenocarcinoma) treated with statins experienced more than double the mortality after lung resection;¹²Nishikawa S, Menju T et al. Statins may have double-edged effects in patients with lung adenocarcinoma after lung resection. Cancer Management and Research. 2019 Apr 18;11:3419-3432. however, see evidence from this study that people with mutant p53 had better survival when treated with statins in How can statins help you? What the research says ›

People treated with atorvastatin have shown a slightly higher risk of lung cancer,¹³Fujimoto M, Higuchi T, Hosomi K, Takada M. Association between statin use and cancer: data mining of a spontaneous reporting database and a claims database. International Journal of Medical Sciences. 2015 Jan 22;12(3):223-33. although statins as a whole show only a weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward slightly higher risk of lung cancer¹⁴Vinogradova Y, Coupland C, Hippisley-Cox J. Exposure to statins and risk of common cancers: a series of nested case-control studies. BMC Cancer. 2011 Sep 26;11:409. or no increased risk.¹⁵Fujimoto M, Higuchi T, Hosomi K, Takada M. Association between statin use and cancer: data mining of a spontaneous reporting database and a claims database. International Journal of Medical Sciences. 2015 Jan 22;12(3):223-33; Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010 May 20;340:c2197.

Lymphoma

People with diffuse large B-cell lymphoma treated with statins showed a weak trend toward worse event-free survival.¹⁶Koo YX, Tan DSW et al. Effect of concomitant statin, metformin, or aspirin on rituximab treatment for diffuse large B-cell lymphoma. Leukemia & Lymphoma. 2011 Aug;52(8):1509-16.

Ovarian cancer

People with clear cell cancer treated with statins showed a weak trend toward higher mortality;¹⁷Visvanathan K, Modur S, Artama M, Murtola T. Lipophilic statins show promise for treatment of epithelial ovarian cancer. Cancer Research. 2020 Aug;80(16suppl):5782-5782. however, see evidence of lower mortality among people with other types of ovarian cancer in How can statins help you? What the research says ›

Pancreatic cancer

People treated with statins, especially simvastatin, rosuvastatin, or atorvastatin, have shown a moderately higher risk of pancreatic cancer.¹⁸Fujimoto M, Higuchi T, Hosomi K, Takada M. Association between statin use and cancer: data mining of a spontaneous reporting database and a claims database. International Journal of Medical Sciences. 2015 Jan 22;12(3):223-33.

Prostate cancer

People treated with statins, especially rosuvastatin, atorvastatin, pitavastatin, or lovastatin, have shown a moderately higher risk of prostate cancer in some studies¹⁹Fujimoto M, Higuchi T, Hosomi K, Takada M. Association between statin use and cancer: data mining of a spontaneous reporting database and a claims database. International Journal of Medical Sciences. 2015 Jan 22;12(3):223-33; Vinogradova Y, Coupland C, Hippisley-Cox J. Exposure to statins and risk of common cancers: a series of nested case-control studies. BMC Cancer. 2011 Sep 26;11:409. but not others.²⁰Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010 May 20;340:c2197. Higher cumulative doses of statins may increase the risk.²¹Chang CC, Ho SC, Chiu HF, Yang CY. Statins increase the risk of prostate cancer: a population-based case-control study. Prostate. 2011 Dec;71(16):1818-24.

Skin cancer

People treated with hydrophilic statins, especially lovastatin or simvastatin, have shown slightly higher risk of skin cancer (melanoma, basal cell carcinoma, or squamous cell carcinoma);²²Wang D, Dai S et al. Association between statins exposure and risk of skin cancer: an updated meta-analysis. International Journal of Dermatology. 2023 Nov;62(11):1332-1344. however, see evidence from this study that hydrophilic statins had a protective effect on risk of basal cell carcinoma but no effect on other types of skin cancer in How can statins help you? What the research says ›

People treated with statins have shown a weak trend toward higher risk of non-melanoma skin cancer,²³Jeong GH, Lee KH et al. Effect of statin on cancer incidence: an umbrella systematic review and meta-analysis. Journal of Clinical Medicine. 2019 Jun 8;8(6):819. but no increased risk is seen across all types of skin cancer combined.²⁴Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010 May 20;340:c2197.

Stomach cancer

People treated with pitavastatin have shown a substantially higher risk of stomach (gastric) cancer.²⁵Fujimoto M, Higuchi T, Hosomi K, Takada M. Association between statin use and cancer: data mining of a spontaneous reporting database and a claims database. International Journal of Medical Sciences. 2015 Jan 22;12(3):223-33. 

Thyroid cancer

Regular statin use is linked to higher risk of thyroid cancer.²⁶Hung SH, Lin HC, Chung SD. Statin use and thyroid cancer: a population-based case-control study. Clinical Endocrinology (Oxford) 2015; 83: 111-116.

Side effects/adverse events

Common side effects

Side effects reported in studies include these:²⁷Beckerman J. Side effects of cholesterol-lowering statin drugs. WebMD. July 25, 2016. Viewed November 30, 2017; Lim SH, Kim TW et al. A randomised, double-blind, placebo-controlled multi-centre phase III trial of XELIRI/FOLFIRI plus simvastatin for patients with metastatic colorectal cancer. British Journal of Cancer. 2015 Nov 17;113(10):1421-6; Goss GD, Jonker DJ et al. A phase I study of high-dose rosuvastatin with standard dose erlotinib in patients with advanced solid malignancies. Journal of Translational Medicine. 2016 Mar 31;14:83; Sondergaard TE, Pedersen PT et al. A phase II clinical trial does not show that high dose simvastatin has beneficial effect on markers of bone turnover in multiple myeloma. Hematological Oncology. 2009 Mar;27(1):17-22; Thibault A, Samid D et al. Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. Clinical Cancer Research. 1996 Mar;2(3):483-91.

Statins also carry warnings of the following possible side effects:²⁸Beckerman J. Side effects of cholesterol-lowering statin drugs. WebMD. July 25, 2016. Viewed June 11, 2024; Cholesterol-lowering drugs get labeling changes. US Food & Drug Administration. May 22, 2015. Viewed July 15, 2024.

A large analysis of more than 2 million patients from the UK concluded that individual statins were not significantly associated with risk of Parkinson’s disease, rheumatoid arthritis, venous thromboembolism, or osteoporotic fracture. In fact, possible slight protective effects may exist for individual statins against Parkinson’s disease and venous thromboembolism.²⁹Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010 May 20;340:c2197.

Statins and CoQ10

Statins’ effects on muscle function may be due to their depletion of the naturally occurring antioxidant coenzyme Q-10 (CoQ10). CoQ10 is necessary for healthy muscle function, including the muscles in the heart. It also helps prevent toxic side effects from cancer treatments including chemotherapy and radiation therapy³⁰Takimoto M, Sakurai T et al. [Protective effect of CoQ 10 administration on cardial toxicity in FAC therapy]. [Article in Japanese]. Gan To Kagaku Ryoho. 1982 Jan;9(1):116-21. and protects the heart from cardiotoxicity caused by anthracyclines.³¹Iarussi D, Auricchio U et al. Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. Molecular Aspects of Medicine. 1994;15 Suppl:s207-12. Supplementation with CoQ10 during treatment with statins may be appropriate.

Serious side effects

Increased risks of moderate or serious liver dysfunction, acute renal failure, and cataract. Adverse effects were similar across statin types for each outcome except liver dysfunction where risks were highest for fluvastatin. A dose-response effect was apparent for acute renal failure and liver dysfunction.³²Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010 May 20;340:c2197. Liver function test (LFT) monitoring is necessary. Your physician should check liver function at baseline, approximately 12 weeks after starting statin therapy, and then at 12 months.

Rare, but potentially serious side effects include these:³³Beckerman J. Side effects of cholesterol-lowering statin drugs. WebMD. April 17, 2024. Viewed June 11, 2024; Goss GD, Jonker DJ et al. A phase I study of high-dose rosuvastatin with standard dose erlotinib in patients with advanced solid malignancies. Journal of Translational Medicine. 2016 Mar 31;14:83; Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010 May 20;340:c2197.

• Myositis (inflammation of the muscles); the risk of muscle injury increases when certain other medications are taken with statins.
• Elevated levels of CPK (creatine kinase), a muscle enzyme that when elevated, can cause muscle pain, mild inflammation, and muscle weakness. This condition, though uncommon, can take a long time to resolve.
• Rhabdomyolysis (extreme muscle inflammation and damage). With this condition, muscles all over the body become painful and weak. The severely damaged muscles release proteins into the blood that collect in the kidneys. The kidneys can become damaged trying to eliminate a large amount of muscle breakdown caused by statin use. This can ultimately lead to kidney failure or even death. Fortunately, rhabdomyolysis is extremely rare.
• Moderate or serious liver dysfunction
• Acute renal failure

Diabetes promotion

Use of statins has shown small but significant increases in markers or incidence of diabetes among people with either adequate or altered glycemic control.³⁴Alvarez-Jimenez L, Morales-Palomo F, Moreno-Cabañas A, Ortega JF, Mora-Rodríguez R. Effects of statin therapy on glycemic control and insulin resistance: a systematic review and meta-analysis. European Journal of Pharmacology. 2023 May 15;947:175672; Naci H, Brugts J, Ades T. Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circulation. Cardiovascular Quality and Outcomes. 2013 Jul;6(4):390-9. Discontinuing statins did not show any effect on insulin resistance, either fasting or after a meal, among prediabetic people with high cholesterol.³⁵Alvarez-Jimenez L, Morales-Palomo F, Moreno-Cabañas A, Ortega JF, Mora-Rodriguez R. Statins effect on insulin resistance after a meal and exercise in hypercholesterolemic pre-diabetic individuals. Scandinavian Journal of Medicine & Science in Sports. 2022 Sep;32(9):1346-1355. 

Helpful link

Hormone side effects

Statins use is not linked to decreasing cortisol levels below normal. Lipophilic statins, but not hydrophilic statins, led to higher plasma cortisol levels in a combined analysis of studies.³⁶Sahebkar A, Rathouska J, Simental-Mendía LE, Nachtigal P. Statin therapy and plasma cortisol concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials. Pharmacological Research. 2016 Jan;103:17-25.

Myopathy 

In 2019, the FDA added statins to its list of drugs requiring evaluation for the need for regulatory action › due to immune-mediated necrotising myopathy,³⁷Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010 May 20;340:c2197. characterized by “signs of necrosis, or cell death, in the muscles, which causes weakness and fatigue.”³⁸Necrotizing Myopathy. The Myositis Association. Viewed June 11, 2024. 

Vitamin D metabolism

Rosuvastatin can interfere with vitamin D metabolism, preventing the expected rise in serum levels and benefits from supplements.³⁹Kennedy DA, Cooley K et al. Vitamin D: pharmacokinetics and safety when used in conjunction with the pharmaceutical drugs used in cancer patients: a systematic review. Cancers (Basel). 2013 Mar 11;5(1):255-80.

Cognitive function

Generally healthy adults with a serum low-density-lipoprotein cholesterol level of 160 mg/dL or higher showed slightly worse scores on neuropsychological tests when treated with 20 mg lovastatin for 6 months.⁴⁰Muldoon MF, Barger SD et al. Effects of lovastatin on cognitive function and psychological well-being. American Journal of Medicine. 2000 May;108(7):538-46. However, a large analysis of more than 2 million patients from the UK concluded that individual statins were not significantly associated with risk of dementia. In fact, possible slight protective effects may exist for individual statins against dementia.⁴¹Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010 May 20;340:c2197. Also see evidence of lower risk of dementia or cognitive decline among people treated with statins in How can statins help you? What the research says ›

Discontinuation of treatment

Statins as a whole showed no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on discontinuations of cancer treatments because of adverse events, although higher doses of atorvastatin and rosuvastatin were linked to higher rates of discontinuation of treatment.⁴²Naci H, Brugts J, Ades T. Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circulation. Cardiovascular Quality and Outcomes. 2013 Jul;6(4):390-9. 

Interactions with chemotherapy

Because statins may interact with chemotherapy and other drugs, make sure your oncologist and primary care doctor know you are taking statins. You can use the WebMD Interaction Checker › to check for drug interactions.

Interactions with other medications or food 

Statins may interact with medications including these, which may cause potentially serious side effects. Check with your doctor or pharmacist to check for interactions before starting statins or any of the following if you’re already using statins:⁴³Wedro B, Omudhome O. Statins (Cholesterol Drugs). eMedicineHealth. Viewed June 11, 2024.

Do not use/contraindications

Individuals with these situations should not use statins:⁴⁶Wedro B, Omudhome O. Statins (Cholesterol Drugs). eMedicineHealth. Viewed June 11, 2024.

Expert commentary on safety

Statins and CoQ-10

Retired integrative oncologist and CancerChoices advisor Dwight McKee, MD: I think it’s always a good idea to take Co Q10 (or the reduced form, ubiquinol) with RYR [red yeast rice], since inhibition of the enzyme HMG COA reductase (the target of statins, and also the target of the autoimmune response that can be triggered by taking statins), also prevents the body’s ability to produce Co Q10. Statins should always be accompanied by CoQ-10 or ubiquinol.

Integrative physician and CancerChoices advisor Keith Block, MD, concurs: “Because statins deplete coenzyme Q10 especially from your muscle cells, particularly your heart, I advise patients on statins to take at least 30 mg of coQ10 per day, and 200 mg or considerably more if they are taking any heart-damaging medications such as Adriamycin or Herceptin.”⁴⁷Block K. Life Over Cancer. New York: Bantam Dell. 2009. p. 522; Deichmann R, Lavie C, Andrews S. Coenzyme q10 and statin-induced mitochondrial dysfunction. Ochsner Journal. 2010;10(1):16-21.

Statins and insomnia or cognitive function

Retired integrative oncologist and CancerChoices advisor Dwight McKee, MD: Although they have been observed, such side effects as insomnia and decrease in cognitive function are still questionable. It is very important for a pharmacist to suggest a less lipophilic member of the statin group when dealing with patients who have an existing or potential condition of insomnia or decreased cognitive function.”⁴⁸Motylev A. Lipophilic or hydrophilic nature of statins is important. Pharmacy Times. March 1, 2005. Viewed November 30, 2017.

Thus a trade-off exists: the more lipophilic statins are considered to have greater anticancer potential but also greater risks for cognitive problems. Therefore, potential benefits of statin use solely for anticancer purposes need to be carefully weighed for those with insomnia or at risk of decreased cognitive function.

Statins and autoimmune conditions

Retired integrative oncologist and CancerChoices advisor Dwight McKee, MD: It’s been known for a long time that statins can cause muscle inflammation, pain, and weakness. In 2013 it was found that there is a subset of these side effects that are autoimmune mediated—that is, the person’s immune system reacts against the same enzyme target as the statins.⁴⁹Hamann PD, Cooper RG, McHugh NJ, Chinoy H. Statin-induced necrotizing myositis—a discrete autoimmune entity within the “statin-induced myopathy spectrum.” Autoimmunity Reviews. 2013 Oct;12(12):1177-81. This happens in about 2-3 per 100,000 statin users, so it’s pretty rare. I think it probably should be added to the list, with that proviso that the incidence appears to be about 2-3 persons per 100,000 statin users. I doubt there are any data, but the precautionary principle would certainly dictate that people with autoimmune disease avoid statins.

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