Why Statins Work Well for Some People and Cause Side Effects in Others

Do Statins Work for Everyone?

Being told you have “high cholesterol” can feel unsettling, particularly if medication is mentioned early in the conversation. But cholesterol itself is not a disease, and rising cholesterol does not mean damage has already occurred.

To understand why statins help some people easily while others struggle with side effects or limited benefit, it helps to start with the basics, and then look at what cholesterol tests alone cannot explain.

What Is Cholesterol, and Why Do We Need It?

Cholesterol is a fat-like molecule that your body uses every day. It plays essential roles in:

• Building and maintaining cell membranes

• Helping to produce steroid hormones such as cortisol, oestrogen, and testosterone

• Helping to produce vitamin D

• Supporting digestion through bile acid production

Your liver produces most of the cholesterol you need, with a smaller contribution from food. Cholesterol is not harmful by default. Problems arise when too much cholesterol accumulates in artery walls over time.

Why Can Too Much Cholesterol Be Harmful?

Cholesterol does not dissolve in blood. To move safely through the bloodstream, it is packaged into microscopic transport particles called lipoproteins. Some of these particles can enter the lining of blood vessels. When cholesterol-carrying particles circulate at high levels for many years:

• Cholesterol can be deposited within artery walls

• Plaques slowly form and harden

• Blood flow may become restricted

This process, known as atherosclerosis, develops gradually and often without symptoms. Cardiovascular risk is shaped less by a single cholesterol reading and more by long-term exposure.

What Lifestyle Choices Can Help When Cholesterol Is Rising?

Medication is not the only lever. For people with mildly to moderately elevated cholesterol, lifestyle changes can meaningfully influence lipid levels and long-term risk. Common clinician-recommended strategies include:

• Dietary patterns that reduce excess saturated fats and ultra-processed foods while increasing fibre-rich plant foods

• Regular physical activity, which improves lipid metabolism and insulin sensitivity

• Weight and waist management, particularly reducing visceral abdominal fat

• Smoking cessation, which improves vascular health

• Moderating alcohol intake, as higher intake can worsen triglycerides and cholesterol patterns

Lifestyle changes can lower cholesterol directly and also improve how the body responds to medication if it is needed later.

Statins are among the most widely prescribed medications in the world because they reliably reduce cardiovascular risk in many people.

They work primarily by:

• Reducing cholesterol production in the liver

• Increasing the liver’s ability to remove cholesterol-carrying particles from the bloodstream

As a result, statins typically lower:

• LDL cholesterol

• Non-HDL cholesterol

• ApoB (the number of atherogenic particles)

For many people, statins are effective, well tolerated, and life-saving. However, statins are not identical drugs, and people do not process them in the same way.

Why Cholesterol Numbers Don’t Explain Statin Response

Cholesterol tests are excellent at estimating risk, but they do not explain how an individual will respond to a specific medication.

Two people can:

• Have similar LDL cholesterol or ApoB levels

• Be prescribed the same statin

• Take similar doses

…and still experience very different outcomes.

One person may see a strong cholesterol reduction with no side effects. Another may experience muscle symptoms, fatigue, or only modest benefit. These differences are not a matter of effort or adherence — they reflect differences in biology.

Why Statins Affect People Differently

For a statin to work, it must be absorbed, transported into liver cells, processed, and cleared from the body. Each step varies between individuals.

Transport into the liver

Some statins rely on transport proteins to enter liver cells efficiently. If this transport is reduced, drug levels may remain higher in the bloodstream and tissues, increasing the likelihood of side effects.

Metabolism and clearance

Statins are processed by different metabolic pathways. Some people break these drugs down slowly, others quickly. This affects both effectiveness and tolerability.

Differences between statins

Statins differ in how readily they enter tissues such as muscle and brain. More hydrophilic statins tend to stay in the bloodstream, while more lipophilic statins penetrate tissues more easily. This can influence side-effect profiles and explains why switching statins often resolves symptoms.

These differences help explain why side effects are often predictable, not random.

ApoB May Be the Target, But How You Get There Matters

From a prevention perspective, many clinicians now focus on reducing ApoB, which reflects the number of cholesterol-carrying particles capable of entering artery walls.

ApoB is a useful treatment target, but it does not dictate how that target should be reached.

Different people may require:

• Different statins

• Different doses

• Or different combinations of lipid-lowering therapies

This more personalised approach to cholesterol treatment is increasingly emphasised by preventive clinicians, including figures such as Peter Attia, who focus on reducing lifetime arterial exposure while maintaining long-term tolerability and adherence.

When Pharmacogenomics Adds Value in Cholesterol Treatment

Pharmacogenomics help your Dr understand how your genes affect your response to certain medications, including statins. If you're prescribed a statin, PGx can help ensure that the risks of side effects are minimised while the dose is optimised. Pharmacogenomic (PGx) testing does not replace cholesterol testing. It complements it by explaining why medications behave differently in different people.

PGx may be particularly helpful if:

• You have experienced statin-related side effects

• LDL or ApoB reduction has been weaker than expected

• You have needed to switch statins more than once

• You take several long-term medications

• Long-term adherence is a concern

By understanding how your genes influence drug transport and metabolism, clinicians can make more informed decisions about medication choice and dosing.

Frequently Asked Questions

Are statin side effects common?

Most people tolerate statins well. Side effects occur in a minority of patients and are often dose- or drug-specific rather than a class effect.

If I had side effects on one statin, can I never take statins again?

Not necessarily. Many people tolerate a different statin or a different dose without problems.

Do cholesterol levels predict statin side effects?

No. Cholesterol numbers describe cardiovascular risk, not how your body handles medication.

Are lifestyle changes still important if I take a statin?

Yes. Lifestyle measures improve overall cardiovascular health and often enhance medication effectiveness.

Can genetics really influence statin response?

Yes. Genetic variation affects drug transport and metabolism and helps explain why people respond differently to the same medication. You can learn more about PGx and the following statins on these pages: Atorvastatin, pravastatin, rosuvastatin and simvastatin.

The bottom line

Cholesterol tests help identify who is at risk. Statins reduce that risk for many people. But how a statin works — and how well it is tolerated — depends on individual biology.

By combining cholesterol testing with pharmacogenomic insight, clinicians can move beyond trial-and-error prescribing toward safer, more effective, and more sustainable cholesterol management.