The cholesterol-lowering medications known as statins are some of the most commonly prescribed drugs in the US. But not everyone can take them without experiencing uncomfortable — or, in some rare cases, dangerous — side effects.
It’s been estimated that up to 20% of patients are unable to tolerate statins because they experience too much muscle pain and muscle damage.
Once medical providers determine that their patient isn’t tolerating statins well, they will prescribe them a statin alternative medication instead. Some of these alternatives have been in use for decades, while others take advantage of recent technological advancements.
In this article, I’ll overview the main alternatives to statins, including natural remedies, lifestyle modifications, and new medications that are still on the horizon. I’ll explain why statin alternatives are safe and how they differ from traditional statins.
Finally, I’ll discuss how you and your healthcare provider can find the best statin or statin alternative to treat your high cholesterol.
Alternatives to Statins
Statin alternatives perform a few general functions.
They can reduce the concentration of so-called “bad cholesterol,” which are also known as low-density lipoprotein, or LDL.
When LDLs build up in your bloodstream, they can form fatty deposits called plaque, which can cause the arteries to narrow and become less flexible (a condition called atherosclerosis).
Some statin alternatives can also raise your concentrations of “good cholesterol,” or high-density lipoprotein (HDL).
HDL absorbs bad cholesterol and carries it back to your liver, where it’s flushed from the body.
Ezetimibe is known as a selective cholesterol absorption inhibitor. It works by decreasing the amount of cholesterol that’s absorbed by the small intestine and transported to the liver via the bloodstream.
This overall makes it easier to clear excess bad cholesterol from the blood. Ezetimibe is often used in combination with other cholesterol reducing medications.
PCSK9 inhibitors are a form of monoclonal antibody therapy that work to lower the production of the PCSK9.
When the body produces less of this protein, cell membrane receptors begin to hold onto more bad cholesterol for longer, which reduces the amount of bad cholesterol in the bloodstream. This therapy is typically given by injection every two to four weeks.
Apheresis is a physical procedure for separating and removing bad cholesterol from the blood. A physical machine, somewhat similar to a kidney dialysis device, draws blood from a patient and then separates out the blood plasma, from which cholesterol is then filtered and removed.
Then the patient’s blood is then pumped back into the body. This therapy is typically given every two weeks.
Medications for high triglycerides
Medications known as fibrates work to decrease triglyceride production in the liver.
Triglycerides are a type of fat found in your blood that can affect heart health alongside cholesterol, and can also lead to pancreatitis if present in too high concentrations. Some fibrate medications may also lead to a decrease of certain kinds of bad cholesterol, and also elevate good cholesterol levels.
Sequestrants, also known as bile acid sequestrants, include cholestyramine (Prevalite, Questran), colestipol (Colestid), and colesevelam (Welchol).
They are often used in combination with other medications like statins or niacin and work by causing bile acid to be secreted in the feces. This then forces the liver to convert bad cholesterol into bile acid to maintain proper acid levels. However, this medication can also raise triglyceride levels.
ACL inhibitors made from bempedoic acid (Nexletol, Nexlizet) have been proven to reduce bad cholesterol, and are sometimes prescribed alongside ezetimibe.
They work by inhibiting a liver enzyme called adenosine triphosphate citrate lyase (ACL), which typically helps to create more cholesterol.
Niacin, a B vitamin, has been shown to help increase good cholesterol levels, and lower bad cholesterol and triglyceride levels. Niacin is able to reduce cholesterol because it drops the number of fatty acids being activated from tissue storage and decreases how much LDL is synthesized.
It increases HDL by preventing the removal of it by liver cells, allowing the body to retain more.
While these are impressive benefits, niacin does not erase all risk for cardiovascular disease.
Niacin therapy also needs to be carefully dosed and monitored, and comes with potential side effects including increased insulin resistance. Plant sterols, meanwhile, provide structural components for plant membranes, similar to how cholesterol provides structure to human cells.
Plant sterols have been shown to reduce cholesterol when consumed in foods (fruits, vegetables, legumes, nuts, seeds) that naturally contain them.
Supplements are also available that provide plant sterols, but evidence supporting their effectiveness is more limited.
Regular exercise, including moderate aerobic exercise and resistance training, has been proven to increase “good” cholesterol and improve overall cholesterol levels.
A diet that keeps trans fats in check, while providing ample soluble fiber, can also keep bad cholesterol levels lower. Reducing stress and quitting smoking can also help your cholesterol profile.
New drugs on the way
There are also a number of promising statin alternatives in the pipeline, including early research into gene therapy. Regulators are currently reviewing Inclisiran, an injectable medication that uses small interfering RNA (siRNA) technology to inhibit PCSK9 protein.
This ultimately leads to less bad cholesterol circulating in the bloodstream.
Inclisiran seems to require less frequent injections than current PCSK9 therapies (every three to six months, versus two to four weeks). Einacumab, which is also in advanced studies, is a monoclonal antibody administered via infusion that blocks a protein associated with high bad cholesterol levels.
It can be used in combination with other cholesterol lowering therapies.
Are Statin Alternatives Safe?
Much like statins themselves, prescription statin alternatives have to go through governmental approval processes to prove their safety and effectiveness.
Your healthcare provider should inform you of any side effects to expect when taking one or more statin alternatives.
Taking natural, alternative supplements to lower cholesterol can be a somewhat riskier bet, because these products aren’t prescribed, tested, and regulated in the same way prescription medications are.
For example, red yeast rice is a traditional Chinese medicine famed for its cholesterol lowering powers.
While it is readily available without a prescription, studies have shown that it contains an identical chemical compound to lovastatin, which means that its use should be monitored by your healthcare provider for side effects in the same way a prescription statin is.
What Are Statins?
Statins are typically the first-line medication prescribed when lifestyle changes alone cannot manage high cholesterol. They’re among the most commonly used drugs in the world.
Statins work by blocking a liver enzyme needed to produce LDL cholesterol.
Typically, when these bad cholesterols build up in your bloodstream, they can form fatty deposits called plaque.
Statins help decrease these risks by slowing the buildup of plaque.
Types of Statins
Some of the most commonly prescribed types of statins include:
- Atorvastatin (Lipitor)
- Simvastatin (Zocor, FloLipid)
- Lovastatin (Altoprev)
- fluvastatin (Lescol XL),
- pitavastatin (Livalo);
- pravastatin (Pravachol);
- rosuvastatin (Crestor, Ezalor)
Some statins stay in your body for shorter amounts of time. These include pravastatin, lovastatin, simvastatin, and fluvastatin.
By contrast, atorvastatin, pitavastatin, and rosuvastatin all stay in the body in medically effective concentrations for longer, up to and beyond a full day.
Lipophilic statins (simvastatin, lovastatin, atorvastatin, and fluvastatin) may be associated with more severe side effects than more hydrophilic statins (pravastatin and rosuvastatin).
Risks and side effects
In some rare cases, statins may cause serious liver, kidney, or muscle damage.
This includes a rare but serious condition called rhabdomyolysis, in which muscle tissue breaks down and releases proteins and electrolytes into the blood.
Symptoms include dark, tea-colored urine, general fatigue and malaise, and extremely sore muscles.
Other side effects of taking statins include:
- Abdominal pain
- Memory loss
- Skin problems
- Muscle weakness
- Muscle pain
- Pregnancy complications
Finding the Best Option
In cases where lifestyle modifications are not working enough on their own to lower cholesterol, health care providers will usually prescribe statins as a preferred first-line treatment.
That’s because they’re especially well-studied, cost-effective, and commonly available.
You should talk to your healthcare provider, however, if you begin to experience any moderate or severe side effects from taking statins, or if you have a history of bad reactions to statins. In these cases, your doctor will usually prescribe some combination of statin alternatives.
To do so, they will take into account your medical history, as well as your current and target cholesterol and triglyceride levels.
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Frequently Asked Questions
K Health articles are all written and reviewed by MDs, PhDs, NPs, or PharmDs and are for informational purposes only. This information does not constitute and should not be relied on for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.
K Health has strict sourcing guidelines and relies on peer-reviewed studies, academic research institutions, and medical associations. We avoid using tertiary references.
Statin intolerance and new lipid-lowering treatments (2021).
Emerging Non-statin Treatment Options for Lowering Low-Density Lipoprotein Cholesterol. (2021).
Fibrate Medications. (2022).
Lipid Lowering Drug Therapy. (2021).
Antilipemic Agent Bile Acid Sequestrants. (2022).