From the Guidelines
Having very low LDL cholesterol levels is generally not harmful for most people. While LDL is often called "bad cholesterol" because high levels increase heart disease risk, extremely low levels (below 40 mg/dL) rarely cause problems 1. Some studies have suggested possible associations between very low LDL and certain conditions like hemorrhagic stroke, cancer, depression, or anxiety, but these relationships aren't clearly established as causal. The body needs some cholesterol for cell membrane structure and hormone production, but it can produce sufficient amounts on its own. Most medical guidelines focus on lowering elevated LDL levels rather than establishing minimum thresholds.
Key Considerations
- If your LDL is very low due to medication like statins or PCSK9 inhibitors, this is typically considered beneficial for cardiovascular health 1.
- However, if you have unexplained extremely low LDL without medication use, it's worth discussing with your healthcare provider to rule out rare genetic conditions or other underlying health issues.
- The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001, which supports the benefit of cholesterol-lowering therapy in high-risk patients and recommends an LDL-C goal of <100 mg/dL 1.
- Recent clinical trials have confirmed the benefits of LDL-lowering therapy in high-risk patients, including those with diabetes, and support the inclusion of patients with diabetes in the high-risk category 1.
Clinical Implications
- Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management, and any person at high risk or moderately high risk who has lifestyle-related risk factors is a candidate for TLC to modify these risk factors regardless of LDL-C level 1.
- When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels 1.
From the Research
Association between Low-Density Lipoprotein (LDL) Cholesterol and Cardiovascular Events
- Studies have shown that lowering LDL cholesterol levels can reduce the risk of cardiovascular events 2, 3, 4.
- However, very low levels of LDL cholesterol have been associated with increased risks of certain complications, such as cancer, hemorrhagic stroke, and other adverse outcomes 2, 5.
- The optimal range of LDL cholesterol levels for cardiovascular health is still a topic of debate, with some studies suggesting that very low levels may be beneficial for high-risk patients 3, while others have found associations between very low LDL cholesterol levels and increased mortality 5.
Safety of Very Low LDL Cholesterol Levels
- Clinical trial evidence has generally not demonstrated correlations between on-treatment LDL cholesterol levels and safety 2.
- However, observational studies have suggested that very low LDL cholesterol levels may be associated with increased risks of certain outcomes, such as stroke-specific mortality 5.
- Further investigation is needed to elucidate the optimal range of LDL cholesterol levels for cardiovascular health in the general population 5.
LDL Cholesterol Lowering Therapies
- Statins are a common therapy for lowering LDL cholesterol levels, and have been shown to be effective in reducing cardiovascular event rates 2, 4.
- Other therapies, such as ezetimibe, have also been shown to be effective in lowering LDL cholesterol levels 4.
- Novel LDL-lowering therapies may also be effective in achieving very low levels of LDL cholesterol 6.