Lipoprotein Subfractionation: Large VLDL Particle Number (NMR)

Optimal Takeaways  

Large VLDL particles are associated with an increased cardiovascular and cardiometabolic disease risk. They are considered atherogenic and are viewed as markers for metabolic syndrome and increased risk of type 2 diabetes, even if triglyceride levels aren’t elevated. Lower levels of large VLDLs likely reflect a decreased risk of cardiometabolic dysfunction and an increased likelihood of metabolic health.

Standard Range: 0.00 – 16.00 nmol/L

The ODX Range: 0.00 – 3.70 nmol/L

Low levels of large VLDLs suggest a reduced risk of cardiovascular disease and represent better metabolic health (Phillips 2015), and likely adherence to healthy lifestyle factors (Si 2021).

High levels of large VLDLs may be associated with atherosclerosis, coronary artery disease risk (Colhoun 2002), metabolic associated/non-alcoholic fatty liver disease (Heeren 2021), insulin resistance, type 2 diabetes, familial hyperlipidemia, overproduction of apoB, familial dyslipidemic hypertension, and increased liver fat which impairs insulin’s ability to suppress large VLDL1secretion (Adiels 2008).

Overview    

Very low-density lipoproteins (VLDL) transport triglycerides from the liver to other tissues in the body. Dyslipidemia observed in insulin resistance, metabolic syndrome, and type 2 diabetes is characterized by the overproduction of large triglyceride-rich VLDLs (VLDL1) in the liver. This process stimulates further lipoprotein changes, including increased levels of atherogenic smaller LDL particles, more remnant particles, and decreased HDL cholesterol. These atherogenic changes can occur several years before the diagnosis of T2DM becomes evident. Production of large VLDLs is influenced by several factors, including the availability of fatty acids from food, adipose tissue, and hepatic synthesis; circulating glucose which can be converted to triglycerides by the liver; brain glucose sensing and insulin sensitivity; and increased buildup of fat in the liver. Large triglyceride-rich VLDLs are precursors to small, dense LDL particles, contributing further to their atherogenic properties (Adiels 2008).

Even though large VLDLs themselves may not be able to penetrate the arterial wall, their remnants can infiltrate the intima, be taken up by macrophages, and contribute to foam cell production and atherosclerotic plaque development (Chapman 2011).

Serum concentrations of large VLDL and triglycerides increased significantly following a high-fat meal, especially in those with triglycerides elevated at baseline (Wojczynski 2011). Research suggests that postprandial lipemia with increases in large VLDL contributes to the formation of highly atherogenic small, dense LDL, as demonstrated in a study of 32 post-myocardial infarction patients (Koba 2003). Increased postprandial levels of large VLDL particles likely reflect increased triglyceride content and have been associated with increased coronary artery calcium, atherosclerosis, and coronary artery disease risk (Colhoun 2002). Administration of omega-3 fatty acids, especially EPA and DHA, can decrease serum levels of large VLDL particles and triglycerides (Bays 2012).

Interestingly, higher levels of large VLDLs were associated with higher hemoglobin levels in men in a Finnish study of 766 health check-up subjects. Prior research suggests that above-optimal hemoglobin may also be associated with an increased risk of atherosclerosis, obesity, insulin resistance, and metabolic syndrome (Hämäläinen 2018). Weight gain of 5% or greater was also associated with an atherogenic profile characterized by an increase in large VLDL particles, while weight loss was related to their reduction. Researchers suggest weight management may be a modifiable cardiovascular risk factor (Mäntyselkä 2012).

The number of large VLDLs (large VLDL-P) and VLDL size were significantly higher in diabetics than nondiabetics in a study looking at low-normal thyroid function and lipoprotein characteristics. The study of 113 subjects found that those with T2DM had significantly higher concentrations of large VLDLs at 7.3 nmol/L versus 3.3 in nondiabetics. Mean VLDL size and levels of triglycerides were significantly higher in diabetics as well (van Tienhoven-Wind 2015).

References  

Adiels, Martin et al. “Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome.” Arteriosclerosis, thrombosis, and vascular biology vol. 28,7 (2008): 1225-36. doi:10.1161/ATVBAHA.107.160192

Bays, Harold E et al. “Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on lipoprotein particle concentration and size in patients with very high triglyceride levels (the MARINE study).” Journal of clinical lipidology vol. 6,6 (2012): 565-72. doi:10.1016/j.jacl.2012.07.001

Chapman, M John et al. “Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management.” European heart journal vol. 32,11 (2011): 1345-61. doi:10.1093/eurheartj/ehr112

Colhoun, Helen M et al. “Lipoprotein subclasses and particle sizes and their relationship with coronary artery calcification in men and women with and without type 1 diabetes.” Diabetes vol. 51,6 (2002): 1949-56. doi:10.2337/diabetes.51.6.1949

Hämäläinen, Päivi et al. “Hemoglobin level and lipoprotein particle size.” Lipids in health and disease vol. 17,1 10. 10 Jan. 2018, doi:10.1186/s12944-018-0655-2

Heeren, Joerg, and Ludger Scheja. “Metabolic-associated fatty liver disease and lipoprotein metabolism.” Molecular metabolism vol. 50 (2021): 101238. doi:10.1016/j.molmet.2021.101238

Koba, Shinji et al. “Small dense LDL phenotype is associated with postprandial increases of large VLDL and remnant-like particles in patients with acute myocardial infarction.” Atherosclerosis vol. 170,1 (2003): 131-40. doi:10.1016/s0021-9150(03)00245-4

Mäntyselkä, Pekka et al. “Weight change and lipoprotein particle concentration and particle size: a cohort study with 6.5-year follow-up.” Atherosclerosis vol. 223,1 (2012): 239-43. doi:10.1016/j.atherosclerosis.2012.05.005

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Phillips, Catherine M, and Ivan J Perry. “Lipoprotein particle subclass profiles among metabolically healthy and unhealthy obese and non-obese adults: does size matter?.” Atherosclerosis vol. 242,2 (2015): 399-406. Doi:10.1016/j.atherosclerosis.2015.07.040  

Si, Jiahui et al. “Improved lipidomic profile mediates the effects of adherence to healthy lifestyles on coronary heart disease.” eLife vol. 10 e60999. 9 Feb. 2021, doi:10.7554/eLife.60999

van Tienhoven-Wind, Lynnda, and Robin P F Dullaart. “Low normal thyroid function as a determinant of increased large very low density lipoprotein particles.” Clinical biochemistry vol. 48,7-8 (2015): 489-94. doi:10.1016/j.clinbiochem.2015.01.015

Wojczynski, Mary K et al. “High-fat meal effect on LDL, HDL, and VLDL particle size and number in the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN): an interventional study.” Lipids in health and disease vol. 10 181. 18 Oct. 2011, doi:10.1186/1476-511X-10-181