What is considered too low for Low Density Lipoprotein (LDL) cholesterol?

From the Guidelines

Low-density lipoprotein (LDL) cholesterol is generally considered too low when it falls below 40 mg/dL (1.0 mmol/L), but the most recent and highest quality study suggests that the goal of treatment is to lower LDL-C to <1.4 mmol/L (<55 mg/dL) and to reduce it by at least 50% if the baseline LDL-C level is 1.8-3.5 mmol/L (70-135 mg/dL) 1. When considering the potential risks and benefits of low LDL levels, it's essential to weigh the evidence from recent clinical trials.

• The 2021 European Heart Journal study 1 provides the most up-to-date guidance on managing dyslipidaemia in patients with established coronary artery disease (CAD).
• The study recommends that the goal of treatment is to lower LDL-C to <1.4 mmol/L (<55 mg/dL) and to reduce it by at least 50% if the baseline LDL-C level is 1.8-3.5 mmol/L (70-135 mg/dL).
• While older studies, such as those from 2004 1, discuss the potential benefits and risks of lowering LDL-C to very low levels, the most recent evidence should take precedence in guiding clinical decision-making. Some individuals with very low LDL levels (below 40 mg/dL) might experience symptoms like neurological issues, hemorrhagic stroke risk, mood changes, or hormonal imbalances, though these concerns remain somewhat controversial in medical literature. People taking intensive statin therapy or PCSK9 inhibitors like evolocumab (Repatha) or alirocumab (Praluent) may achieve very low LDL levels. If you're experiencing symptoms and have extremely low LDL, consult your healthcare provider, who might consider adjusting medication dosage. The body needs some cholesterol for cell membrane formation, hormone production, and vitamin D synthesis, which explains why extremely low levels might be problematic for some individuals. Most people should aim for LDL levels below 100 mg/dL for general health, or below 70 mg/dL if they have cardiovascular disease or diabetes.

From the Research

Low Density Cholesterol Levels

• The optimal target level of low-density lipoprotein cholesterol (LDL-C) is a topic of ongoing debate, with some studies suggesting that there is a "threshold" value below which the incidence of cardiovascular events is no longer reduced 2.
• A study published in BMC Medicine found that the risk of cardiovascular events decreased monotonically until the LDL-C level was lowered to 70 mg/dl, but when the level was further reduced, the risk was independent of LDL-C 2.
• Another study published in Current Opinion in Lipidology discussed the importance of accurate assessment of LDL-C levels, particularly at very low levels, and proposed a novel method for estimating LDL-C that is more accurate than traditional methods 3.
• The study suggested that LDL-C values below 70 mg/dl are considered optimal for high-risk patients, and that accurate assessment of LDL-C levels at this level is crucial 3.

Comparison of LDL-C Levels

• A study published in The New England Journal of Medicine compared the effects of extended-release niacin and ezetimibe on LDL-C levels and found that niacin therapy significantly reduced LDL cholesterol and triglyceride levels, while ezetimibe reduced the HDL cholesterol and triglyceride levels 4.
• The study also found that greater reductions in the LDL cholesterol level in association with ezetimibe were significantly associated with an increase in the carotid intima-media thickness, suggesting that overly low LDL-C levels may not be beneficial 4.
• Another study published in the Journal of the American College of Cardiology found that coadministration of ezetimibe/simvastatin with extended-release niacin resulted in significantly greater reductions in LDL-C and other lipid parameters, but also increased the risk of flushing 5.

Safety and Efficacy

• A study published in Endocrinology and Metabolism Clinics of North America discussed the efficacy and safety of available statins, bile acid sequestrants, and ezetimibe in the treatment of hyperlipidemia, and found that statins are the most potent drugs for lowering LDL-C and are well tolerated in most patients 6.
• The study also found that the addition of a bile acid sequestrant or ezetimibe to a statin produces additional LDL-C reduction, allowing many patients to reach LDL-C targets 6.