Should I take statins?

Statins are considered a tool to extend life, with new guidelines suggesting their use as early as age 30 for individuals with cardiovascular risk factors. While they can reduce cardiovascular benefit, especially when combined with ezetimibe, and alternative therapies like bempedoic acid exist for statin-intolerant individuals, their efficacy is often presented using relative rather than absolute risk.

However, concerns persist regarding statins' potential negative impact on organs requiring cholesterol, such as the brain, and their association with increased dementia risk, particularly with lipophilic statins. The causal link between elevated LDL cholesterol and heart disease also remains unproven by some experts, who suggest dietary changes as a more effective approach for those without a prior heart attack.

For individuals with borderline or not very high LDL, low HDL may contribute to initiating statin therapy. A polypill combining low-dose statins, blood pressure medications, and other components can reduce risk factors. Bempedoic acid may be a suitable oral therapy for women with statin intolerance who cannot achieve LDL control with statins.

• 01The first statins were derived from mold toxins, specifically from red yeast rice (Paul Saladino).
• 02New heart disease guidelines suggest statins for individuals as early as age 30 (David Sinclair).
• 03Low HDL may contribute to initiating statin therapy when LDL is borderline or not very high (Peter Attia).
• 04Dietary changes can reduce cardiovascular risk more effectively than statins for individuals who have not had a heart attack (Paul Saladino).
• 05David Sinclair accepts potential long-term risks of statins due to his family history of cardiovascular disease (Andrew Huberman, David Sinclair).
• 06Ezetimibe added to statins further reduces cardiovascular benefit and is supported by mendelian randomization trials (Peter Attia).
• 07Bempedoic acid may be a suitable oral therapy for women with statin intolerance who cannot achieve LDL control with statins (Peter Attia, Andrew Huberman).
• 08Statins can be used as a tool to keep people alive longer, potentially for short durations (Peter Attia, David Sinclair).
• 09Bempedoic acid has less muscle soreness than placebo but not zero, and is more hepatoselective than rosuvastatin (Peter Attia, Rhonda Patrick, Paul Saladino).
• 10Women with FH experience the same onset of cardiovascular disease as men due to under-treatment with statins because of pregnancy concerns (Peter Attia).
• 11Current cardiovascular risk assessment guidelines allow for individualized statin therapy based on overall atherosclerotic risk, not just LDL cholesterol (Peter Attia).
• 12The lowest all-cause mortality is associated with LDL-C around 140 mg/dL in those not on statins and around 89 mg/dL in those on statins (Paul Saladino).
• 13Patients with the lipid triad (low HDL and high triglycerides) had significantly lower event-free survival in the 4S trial (Paul Saladino).
• 14A polypill combining low-dose statins, blood pressure medications, and potentially other components can reduce risk factors (Peter Attia).
• 15Lowering LDL cholesterol through cholesterol synthesis inhibition may negatively impact organs like the brain, which require cholesterol (Peter Attia).
• 16The causal link between elevated LDL cholesterol and heart disease remains unproven (Paul Saladino).
• 17A significant percentage of patients with elevated apob levels are placed on statins and PCSK9 inhibitors (Paul Saladino).
• 18Taking statins is a less ideal approach than removing the source of the problem, such as consuming seed oils (Paul Saladino).
• 19Severe hypolipidemia is clinically associated with an increased incidence of bacterial pneumonia and other infections (Paul Saladino).
• 20Statins can have widespread adverse effects on muscle metabolism over time (Rhonda Patrick).
• 21Using LDL cholesterol as the sole measure of statin efficacy may be misleading; attention should shift to lipoprotein particles (Rhonda Patrick, Paul Saladino).
• 22Lipophilic statins that cross the blood-brain barrier may increase dementia risk by inhibiting cholesterol production in the brain (Paul Saladino).
• 23Statin trials often present cardiovascular risk reduction as a misleading relative risk rather than an absolute risk (Paul Saladino).
• 24Assessing heart health solely based on subjective feeling is insufficient; objective measurements like EKG, blood panels, and blood pressure are standard (Bryan Johnson).
• 25Liver function tests (AST/ALT) are not reliable biomarkers for assessing statin toxicity (Peter Attia).
• 26Statins may worsen diabetes by inhibiting the formation of heme and coenzyme Q10 (Paul Saladino).
• 27Gemfibrozil raises statin levels significantly, increasing the risk of myositis and rhabdomyolysis, whereas fenofibrate does not carry this risk when used with a statin (Peter Attia).
• 28Doctors would react with alarm to a lipid panel showing total cholesterol of 350, LDL of 250, HDL of 79, and triglycerides of 59, and immediately prescribe statins (Paul Saladino).
• 29Statin observed risk reduction is less than that seen in Mendelian randomization studies (Peter Attia).
• 30Statin use may impair cholesterol synthesis in the brain, potentially impacting cognition (Peter Attia, Andrew Huberman, Paul Saladino).
• 31Fenofibrate trials missed primary outcomes but hit secondary outcomes (Peter Attia).
• 32Trials are cleaner and more informative when not confounded by other drugs like statins (Peter Attia).
• 33Statins inhibit cholesterol synthesis and upregulate LDL receptors, providing immune suppression and improved endothelial health (Peter Attia).
• 34The brain synthesizes its own cholesterol and is vulnerable to cholesterol synthesis inhibitors (Peter Attia).
• 35The four main statins worth prescribing are rosuvastatin, atorvastatin, pitavastatin, and sometimes pravastatin (Rhonda Patrick).
• 36Women under 55 were less likely than men to be on a statin two months after myocardial infarction in secondary prevention studies (Peter Attia).
• 37Some clinicians use antihypertensives with the intention of getting patients off those drugs instead of prescribing statins (Paul Saladino).
• 38Dietary interventions have smaller effects on heart disease risk markers compared to statins (Rhonda Patrick).
• 39Statins can cause intractable muscle soreness in about 5% of the population (Peter Attia).
• 40A significant portion of the panel recommending lower statin prescription thresholds had financial ties to cholesterol-lowering drug manufacturers (Paul Saladino).
• 41Documentaries and online content have instilled fear regarding the safety of statins (Peter Attia).
• 42Statins and PCSK9 inhibitors are not universally beneficial and should not be mandatory for the general population (Paul Saladino).

Concerns exist about taking lipid-lowering drugs like statins for extended periods, particularly for younger individuals (30s-50s). The exact beneficial mechanisms of statins are still debated, with questions remaining about whether LDL cholesterol reduction or other pathways are primarily responsible. Statins and other relatively new drugs may have long-term implications not fully understood from shorter-term clinical trials, necessitating post-marketing surveillance. The relationship between statins and diabetes is not fully understood. Lipophilic statins like simvastatin and atorvastatin may pose a greater risk to cognition and memory than hydrophilic statins due to their ability to cross the blood-brain barrier. The role of further arterial calcification while on a statin, versus not on a statin, is not understood. The long-term effects of taking a low dose of statin and bempedoic acid are unknown.

It is not yet known if a randomized, blinded trial will specifically test statins' effect on Alzheimer's disease and dementia risk as a primary outcome. Such a trial would significantly clarify the cognitive risks associated with statin use.