Will statins give you muscle pain? What your genes can tell you.

Statins are used by tens of millions of people worldwide for lowering cholesterol levels.[ref] This type of medication is nearly always top the list of most prescribed in the US, with Lipitor (a type of statin) as the most prescribed drug in the US as of July 2019.[article]

Genetic variants combine with statin usage to cause muscle pain for some individuals. Learn how to check your genes and what you can do about statin muscle pain.

Statins and myopathy

One side effect of statins is myopathy, or muscle pain and weakness.  Myopathy can be severe, leading to the breakdown of muscles and the risk of renal failure.

The risk of severe myopathy with statins is small, but milder myotoxicity is found in 7 to 29% of patients. Essentially, this means that less severe, yet still 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 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…

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.[ref]


Genetic Variant:

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.

Members: Select your data file if you don’t see your genotype below

Check your genetic data for rs4149056 (23andMe v4, v5; AncestryDNA):

  • T/T: typical
  • C/T: reduced breakdown of some drugs, a 5-fold increased risk of myopathy with statins[ref]
  • C/C: reduced breakdown of some drugs; up to a 17-fold increase in the risk of myopathy with statins[ref][ref][ref][ref]

Members: Your genotype for rs4149056 is .


Lifehacks for reducing muscle pain with statins:

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:


Related Genes and Topics:

CYP2C9 GENETIC VARIANTS AND DRUG METABOLISM
Have you ever wondered why certain medications don’t work well for you? Genetic variants can change how fast or how slow the medication is broken down in your body.

LDL CHOLESTEROL
Heart disease is the leading cause of death in the US and around the world, and high LDL-cholesterol levels have been linked in many studies to increased heart disease. Standard medical advice on ideal cholesterol levels and cardiovascular disease is often confusing, ever-changing, and sometimes downright contradictory.