Reducing triglyceride levels
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Dietary Approaches for Reducing Triglyceride Levels
Switching from saturated fats to polyunsaturated fats in the diet can significantly lower serum triglyceride levels. Studies show that diets high in polyunsaturated fat reduce triglycerides by about 35% compared to diets high in saturated fat, with the greatest benefit seen in individuals with the highest baseline triglyceride levels. This effect is mainly due to changes in very low density lipoprotein (VLDL) triglycerides, and is observed in both healthy individuals and those with hyperglyceridaemia .
Pharmacological Interventions: New and Established Therapies
Olezarsen and Apolipoprotein C-III Targeting
Olezarsen, an antisense oligonucleotide that targets apolipoprotein C-III (APOC3), has shown promising results in reducing triglyceride levels. In clinical trials, monthly injections of olezarsen reduced triglyceride levels by about 50% compared to placebo, with additional reductions in apolipoprotein B and non-HDL cholesterol, and no major safety concerns . Targeting APOC3 is a new and effective approach for triglyceride lowering.
Pemafibrate and Fibrates
Pemafibrate, a selective PPARα modulator, lowers triglyceride levels by about 26% in patients with type 2 diabetes and mild-to-moderate hypertriglyceridemia. However, despite these reductions, pemafibrate did not lower the incidence of cardiovascular events compared to placebo . This highlights that while fibrates and similar drugs can lower triglycerides, their impact on cardiovascular outcomes may be limited Pradhan2022Pirillo2023.
Retatrutide and ANGPTL3/8 Inhibition
Retatrutide, a multi-receptor agonist, reduces triglycerides by up to 35% in patients with type 2 diabetes. This effect is linked to a dose-dependent reduction in ANGPTL3/8, a potent inhibitor of lipoprotein lipase, suggesting a novel mechanism for lowering triglyceride-rich lipoproteins .
FGF21 Analogs
FGF21 analogs lower plasma triglycerides by reducing the secretion of VLDL triglycerides from the liver and increasing the breakdown of triglyceride-rich lipoproteins in adipose tissue. This dual mechanism makes FGF21 a promising candidate for triglyceride reduction .
Omega-3 Fatty Acids for Triglyceride Management
Prescription omega-3 fatty acids, especially at doses of 4 grams per day, can lower triglyceride levels by 30% or more. Both EPA+DHA and EPA-only formulations are effective, with EPA-only not increasing LDL cholesterol. High-dose EPA (as in the REDUCE-IT trial) not only lowers triglycerides but also reduces major cardiovascular events by 25% in high-risk patients Marston2019Mason2021Skulas-Ray2019. However, other omega-3 formulations and mixed fatty acids have not consistently shown cardiovascular benefits despite lowering triglycerides .
Triglyceride Lowering and Cardiovascular Risk
Lowering triglycerides is associated with a modest reduction in cardiovascular events and cardiovascular-specific mortality, especially in people with diabetes. However, the benefit is not seen for stroke or all-cause mortality, and the reduction in cardiovascular risk is most pronounced when triglyceride lowering is accompanied by reductions in atherogenic lipoproteins such as apolipoprotein B Pirillo2023Yang2023Marston2019. The effectiveness of triglyceride-lowering therapy for reducing cardiovascular risk depends on the specific drug and patient population Pirillo2023Marston2019Mason2021.
Conclusion
Triglyceride levels can be effectively reduced through dietary changes (increasing polyunsaturated fats), prescription omega-3 fatty acids, and new pharmacological agents targeting APOC3 and ANGPTL3/8. While lowering triglycerides is beneficial for reducing cardiovascular events in some populations, especially those with diabetes, not all triglyceride-lowering therapies translate into reduced cardiovascular risk. The greatest benefit appears when triglyceride reduction is accompanied by a decrease in atherogenic lipoproteins. Ongoing research into new therapies and mechanisms will further clarify the best strategies for managing elevated triglycerides and associated cardiovascular risk.
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