From the Guidelines
Low LDL levels are unlikely to have significant effects on cell membranes in terms of morbidity, mortality, and quality of life, as the body has compensatory mechanisms to maintain cellular cholesterol, and clinically significant membrane dysfunction typically occurs only with extremely low LDL levels 1. When considering the effects of low LDL on cell membranes, it is essential to prioritize the most recent and highest quality studies. The European Heart Journal study from 2021 1 provides valuable insights into the relationship between low LDL levels and cell membrane function. According to this study, very low LDL levels, whether from genetic conditions or intensive lipid-lowering therapy, may compromise cellular functions dependent on membrane integrity. However, the study also notes that the body has compensatory mechanisms to maintain cellular cholesterol, and clinically significant membrane dysfunction typically occurs only with extremely low LDL levels.
Some genetic conditions, such as abetalipoproteinemia and familial hypobetalipoproteinemia, are characterized by very low LDL levels and can provide valuable insights into the long-term effects of low LDL on cell membranes 1. Studies of individuals with these conditions have shown that they can be healthy and free of significant side effects, despite having very low LDL levels. For example, individuals with PCSK9 loss-of-function mutations appear to be healthy, without any evidence of neurocognitive impairment, higher incidence of diabetes, cataracts, or stroke 1.
In terms of lipid-lowering therapy, the use of potent LDL-C-lowering medications, such as high-intensity statins, statin/ezetimibe combination, and PCSK9 inhibitors, can reduce LDL-C levels to an unprecedented extent 1. While these medications can have side effects, the majority of studies have demonstrated no significant association between very low LDL-C and major side effects 1. The FOURIER trial, for example, showed that PCSK9 inhibition reduced the risk of cardiovascular events, even at very low LDL levels 1.
Key points to consider:
- Low LDL levels can affect cell membranes, but the body has compensatory mechanisms to maintain cellular cholesterol 1.
- Very low LDL levels, whether from genetic conditions or intensive lipid-lowering therapy, may compromise cellular functions dependent on membrane integrity, but clinically significant membrane dysfunction typically occurs only with extremely low LDL levels 1.
- Genetic conditions, such as abetalipoproteinemia and familial hypobetalipoproteinemia, can provide valuable insights into the long-term effects of low LDL on cell membranes 1.
- Lipid-lowering therapy, including potent LDL-C-lowering medications, can reduce LDL-C levels to an unprecedented extent, but the majority of studies have demonstrated no significant association between very low LDL-C and major side effects 1.
From the Research
Effects of Low LDL on Cell Membrane
- There is limited direct evidence on the effects of low LDL on cell membrane in the provided studies 2, 3, 4, 5, 6.
- However, it is known that LDL cholesterol plays a crucial role in the structure and function of cell membranes.
- The provided studies primarily focus on the effects of LDL-lowering therapies, such as statins, ezetimibe, and PCSK9 inhibitors, on cardiovascular events and LDL cholesterol levels 2, 3, 4, 5, 6.
- Some studies suggest that very low LDL cholesterol levels (e.g., down to 25 mg/dl) may be safe, but more robust outcome and safety data are required, particularly for PCSK9 inhibitors 4.
- The effects of low LDL on cell membrane are not explicitly discussed in the provided studies, and therefore, it is difficult to draw conclusions on this topic based on the available evidence.