How to decrease oxidized low-density lipoprotein (oxLDL)?

From the Guidelines

To decrease oxidized low-density lipoprotein (oxLDL) levels, focus on a combination of dietary changes, lifestyle modifications, and possibly medications, prioritizing a Mediterranean-style diet, regular physical activity, and weight management, as these approaches have been shown to reduce oxidative stress and improve lipid profiles 1.

Key Recommendations

• Adopt a Mediterranean-style diet rich in antioxidants from fruits, vegetables, nuts, and olive oil, while reducing processed foods and saturated fats.
• Include foods high in polyphenols like berries, dark chocolate, green tea, and red wine (in moderation).
• Engage in regular physical activity of at least 150 minutes per week to improve lipid profiles and reduce oxidative stress.
• Maintain a healthy weight, as excess body fat increases inflammation and oxidative stress.
• Stop smoking and limit alcohol consumption to moderate levels.

Dietary Modifications

• Limit saturated fatty acids and trans-unsaturated fatty acids to 10% and preferably to 7% of energy intake, and replace them with either carbohydrates or monounsaturated fats 1.
• Increase soluble (viscous) fiber intake to 10-25 g/day to enhance plasma LDL cholesterol lowering 1.
• Consider adding plant stanols/sterols (2 g/day) to the diet to further lower LDL cholesterol 1.

Lifestyle Modifications

• Engage in regular physical activity, such as brisk walking, for at least 30 minutes on most days of the week 1.
• Maintain a healthy weight through a combination of diet and exercise, aiming for a body mass index (BMI) between 18.5 and 24.9 kg/m2 1.

Medications

• If lifestyle changes are not sufficient, consider statins like atorvastatin (10-80 mg daily) or rosuvastatin (5-40 mg daily) to lower LDL and potentially reduce oxLDL levels 1.

Additional Considerations

• Antioxidant supplements like vitamin E (400-800 IU daily), vitamin C (500-1000 mg daily), and CoQ10 (100-200 mg daily) may be beneficial, although evidence is varied 1.
• Regular monitoring of lipid profiles and cardiovascular risk factors is essential to adjust treatment plans as needed.

From the FDA Drug Label

The lipid-modifying effects of fenofibric acid seen in clinical practice have been explained in vivo in transgenic mice and in vitro in human hepatocyte cultures by the activation of peroxisome proliferator activated receptor α (PPARα) Through this mechanism, fenofibrate increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein C-III (an inhibitor of lipoprotein lipase activity) The resulting decrease in TG produces an alteration in the size and composition of LDL from small, dense particles (which are thought to be atherogenic due to their susceptibility to oxidation), to large buoyant particles.

To decrease oxLDL, consider using fenofibrate 2, as it can help reduce the susceptibility of LDL to oxidation by increasing the size and buoyancy of LDL particles. Additionally, alirocumab 3 can be used to reduce LDL-C levels, which may also help decrease oxLDL levels.

• Fenofibrate works by activating PPARα, which increases lipolysis and elimination of triglyceride-rich particles from plasma.
• Alirocumab is a PCSK9 inhibitor that can help reduce LDL-C levels by increasing the removal of LDL from the bloodstream.

From the Research

Decreasing oxLDL

To decrease oxLDL, several strategies can be employed, including dietary changes and pharmacological interventions.

• Dietary approaches:
  • Consuming a healthy diet rich in fruits, vegetables, whole-grain, high-fiber foods, and fish, while limiting saturated and trans fats, can help reduce cholesterol levels 4.
  • Replacing saturated fat with monounsaturated fatty acids (MUFAs) or n-6 polyunsaturated fatty acids (PUFAs) can lower plasma low-density lipoproteins (LDL) cholesterol and improve the LDL/HDL ratio 5.
  • Diets rich in refined carbohydrates can increase fasting and postprandial triglycerides, whereas consuming fiber-rich, low glycemic index (GI) foods can lower LDL cholesterol without detrimental effects on triglycerides 5.
• Pharmacological interventions:
  • Statins are the first-line treatment for reducing cardiovascular events by lowering LDL cholesterol, but additional treatments may be necessary to reach lipid targets 6, 7.
  • Ezetimibe, a cholesterol absorption inhibitor, can lead to additional LDL cholesterol reduction and decreased cardiovascular risk when added to statin therapy 6, 7.
  • Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as alirocumab and evolocumab, can significantly decrease serum LDL cholesterol levels and cardiovascular risk when added to maximally tolerated statin therapy 6, 7.

Lifestyle Modifications

Lifestyle modifications, including dietary changes, weight reduction, and physical activity, can also play a crucial role in controlling dyslipidemias and decreasing oxLDL 5.

• A multifactorial approach, incorporating multiple changes with additive effects, is the best option for achieving and maintaining lifestyle modifications 5.
• The traditional Mediterranean way of life can serve as a useful model for lifestyle modifications 5.

Oxidative Stress and Antibodies to oxLDL

Consuming a healthy diet rich in fruits, vegetables, and low-fat dairy products, and reduced in fat, saturated fat, and cholesterol, can reduce oxidative stress and increase antibodies to oxidized LDL (Ab-oxLDL) 8.

• The DASH diet, which is rich in fruits, vegetables, and low-fat dairy products, and reduced in fat, saturated fat, and cholesterol, has been shown to lower urinary isoprostanes, a marker of oxidative stress, and increase Ab-oxLDL 8.