Statins are used by tens of millions of people worldwide to lower cholesterol levels.[ref]
Statins inhibit the HMG-CoA enzyme to reduce cholesterol synthesis.
Genetic variants combine with statin use to cause muscle pain in some individuals.
There are a number of natural options to reverse the muscle pain.
Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today.
Statins and myopathy
Statins were first discovered in the 1970s from work with fungi. The first statin was isolated from Penicillium in 1973, and later in the 70s, Merck patented lovastatin made from Aspergillus terreus.[ref]
The most common side effect of statins is myopathy, or muscle pain and weakness. Myopathy can be severe, leading to the breakdown of muscles, called rhabdomyolysis, and increased risk of renal failure.
The risk of severe myopathy and kidney failure due to statins is small, but milder myotoxicity occurs in up to 29% of patients. This means that less severe damage occurs, but painful, muscle-related symptoms are present in quite a few patients who take statins.[ref]
Why do statins cause muscle pain?
Statins lower cholesterol levels by inhibiting the hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA) enzyme, which is part of the pathway through which the body synthesizes cholesterol. Blocking this enzyme reduces cholesterol synthesis, leading to an increase in LDL receptor expression. More LDL receptors cause more LDL cholesterol to be removed from the bloodstream.
Before statins can act within the liver cells, though, they have to be transported into the cell via a transport protein, and this is where genetic differences play a big role.
SLCO1B1 rs4149056: statin muscle pain risk
The SLCO1B1 gene codes for the organic anion transporting polypeptide 1B1 (OATP1B1) protein. Genetic variants can cause this transport protein not to function as well, impairing the uptake of the statin.
When the transport protein doesn’t work well, the statin remains longer in circulation in the bloodstream. This causes side effects such as myopathy. The differences are stark – with one copy of a SLCO1B1 variant, there is up to a 5-fold increase in myopathy, and with two copies of the variant, there is up to a 17-fold increase in the odds of myopathy. (see the genotype report section below)[ref][ref]
The ABCG2 gene also encodes a transporter that is involved in cholesterol transport across cell membranes. Genetic variants in ABCG2 are also linked to an increased risk of either muscle pain or liver problems from statins.[ref]
Genotype Report: Statins
The main genetic variant (SNP) that impacts statin side effects is known as SLCO1B1*5 or OATP1B1 -388G>A. You can check your genetic data to see if you carry this variant.
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Doctors regularly check creatine kinase (CK) levels to see if statin users have any muscle damage from statins. An elevated CK level can show minor muscle damage even if it isn’t causing a lot of pain.[ref]
Supplemental CoQ10: A meta-analysis of twelve randomized controlled trials found that CoQ10 supplementation decreased muscle pain from statins.[ref]
Skip the grapefruit and pomegranate: Grapefruit and pomegranate can inhibit CYP3A4, which can then cause an increase in statin absorption in the intestines. [ref]
Try a different statin? One (small) study showed that this variant is associated with myopathy in simvastatin patients but not with atorvastatin.[ref]
Check your other medications:
Carrying this SLCO1B1*5 variant impacts other medications as well. If you are taking a medication that is impacted by this variant, be sure to talk with your doctor if you are having side effects from the medication. (Don’t just stop taking the drug- talk with your doctor first.)
This list of medications impacted by SLCO1B1*5 is not exhaustive, just representative of the studies from the past few years.
Increased risk of chemotherapy-induced amenorrhea[ref]
Modest changes in grazoprevir (hep-C medicine) metabolism[ref]
Elevated estrogen levels and extended time of detectable estrone after aromatase inhibitor treatment (breast cancer)[ref]
Altered levels of letermovir (antiviral for cytomegalovirus)[ref]
Increased risk of liver dysfunction with tegafur-uracil (chemo drug) [ref]
Decreased effectiveness of acitretin (psoriasis medication)[ref]
Altered response to hormone therapy in menopause.[ref]
Increased risk of liver dysfunction with methotrexate (lymphoma patients)[ref]
Decreased survival rate in high-dose methotrexate patients (ALL)[ref]
While not as important as the drugs above, EGCG (from green tea) concentrations are affected by this variant.[ref]
PharmGKB has more information on drugs impacted by the SLCO1B1*5 variant:
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References:
Bai, Xue, et al. “Effects of SLCO1B1 and GATM Gene Variants on Rosuvastatin-Induced Myopathy Are Unrelated to High Plasma Exposure of Rosuvastatin and Its Metabolites.” Acta Pharmacologica Sinica, vol. 40, no. 4, Apr. 2019, pp. 492–99. PubMed, https://doi.org/10.1038/s41401-018-0013-y.
Brackman, Deanna J., et al. “Genome-Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol.” Clinical Pharmacology and Therapeutics, vol. 106, no. 3, Sep. 2019, pp. 623–31. PubMed Central, https://doi.org/10.1002/cpt.1439.
Carr, Daniel F., et al. “Genomewide Association Study of Statin-Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink.” Clinical Pharmacology and Therapeutics, vol. 106, no. 6, Dec. 2019, pp. 1353–61. PubMed, https://doi.org/10.1002/cpt.1557.
Dehghan, Abbas, et al. “Association of Three Genetic Loci with Uric Acid Concentration and Risk of Gout: A Genome-Wide Association Study.” Lancet (London, England), vol. 372, no. 9654, Dec. 2008, pp. 1953–61. PubMed, https://doi.org/10.1016/S0140-6736(08)61343-4.
du Souich, Patrick, et al. “Myotoxicity of Statins: Mechanism of Action.” Pharmacology & Therapeutics, vol. 175, Jul. 2017, pp. 1–16. PubMed, https://doi.org/10.1016/j.pharmthera.2017.02.029.
Harrington, Robert A. “Statins—Almost 30 Years of Use in the United States and Still Not Quite There.” JAMA Cardiology, vol. 2, no. 1, Jan. 2017, p. 66. DOI.org (Crossref), https://doi.org/10.1001/jamacardio.2016.4709.
Ichida, Kimiyoshi, et al. “Decreased Extra-Renal Urate Excretion Is a Common Cause of Hyperuricemia.” Nature Communications, vol. 3, Apr. 2012, p. 764. PubMed Central, https://doi.org/10.1038/ncomms1756.
Lee, Da Hoon, et al. “Association Between ABCG2 Polymorphism and Statin-Induced Adverse Events: A Meta-Analysis.” Cardiovascular Toxicology, vol. 25, no. 11, Nov. 2025, pp. 1761–67. Springer Link, https://doi.org/10.1007/s12012-025-10056-w.
Lee, Hannah H., and Richard H. Ho. “Interindividual and Interethnic Variability in Drug Disposition: Polymorphisms in Organic Anion Transporting Polypeptide 1B1 (OATP1B1; SLCO1B1 ).” British Journal of Clinical Pharmacology, vol. 83, no. 6, Jun. 2017, pp. 1176–84. DOI.org (Crossref), https://doi.org/10.1111/bcp.13207.
Li, Xingang, et al. “The Association between Genetic Polymorphisms and Simvastatin-Induced Myopathy: A Narrative Synthesis of Evidence.” Drug Research, vol. 69, no. 4, Apr. 2019, pp. 185–93. PubMed, https://doi.org/10.1055/a-0677-2944.
Liu, Jia, et al. “ABCG2 Rs2231142 Variant in Hyperuricemia Is Modified by SLC2A9 and SLC22A12 Polymorphisms and Cardiovascular Risk Factors in an Elderly Community-Dwelling Population.” BMC Medical Genetics, vol. 21, no. 1, Mar. 2020, p. 54. PubMed, https://doi.org/10.1186/s12881-020-0987-4.
“SLCO1B1 Variants and Statin-Induced Myopathy — A Genomewide Study.” New England Journal of Medicine, vol. 359, no. 8, Aug. 2008, pp. 789–99. DOI.org (Crossref), https://doi.org/10.1056/NEJMoa0801936.
About the Author:
Debbie Moon is a biologist, engineer, author, and the founder of Genetic Lifehacks where she has helped thousands of members understand how to apply genetics to their diet, lifestyle, and health decisions. With more than 11 years of experience translating complex genetic research into practical health strategies, Debbie holds a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. She combines an engineering mindset with a biological systems approach to explain how genetic differences impact your optimal health.
