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APOB

The need for an advanced understanding of lipidology structure and function in healthcare is growing.   Lipoprotein testing provides valuable insights into an individual's lipid profile, aiding in the assessment of cardiovascular risk and guiding interventions above and beyond the standard lipid panel.  

Apolipoprotein B (ApoB) is a critical player in lipid metabolism and cardiovascular health. 

As a component of low-density lipoprotein (LDL) particles, ApoB carries cholesterol through the bloodstream out to various tissues in the body. Given its pivotal role in atherosclerosis development and cardiovascular disease risk, understanding ApoB has become paramount in preventive medicine. 

In this article we delve into the significance of ApoB, exploring its function, the importance of ApoB blood testing, strategies to reduce ApoB levels, testing options, interpretation, and natural approaches to optimize ApoB levels. By elucidating these aspects, we aim to provide individuals with valuable insights into managing their cardiovascular health effectively.

Understanding ApoB

What is ApoB?

Apolipoprotein B (ApoB) is a crucial protein found in lipoproteins, serving as a structural component and aiding in lipid transport throughout the body. It exists in two main forms: ApoB-48 and ApoB-100. 

Apolipoprotein B (ApoB) is a protein that plays a crucial role in lipid metabolism and transport. It is the primary protein component of atherogenic particles such as very low density lipoprotein (VLDL) particles, intermediate-density lipoprotein (IDL) particles, low-density lipoprotein (LDL) particles and lipoprotein a Lp(a) particles.  

These particles are responsible for carrying cholesterol and triglycerides in the bloodstream and depositing them into cells and tissues. ApoB acts as a ligand for LDL receptors, allowing the uptake of LDL particles by cells that require cholesterol for various cellular processes.

In humans, apoB100 is primarily synthesized in the liver, and apoB48 is primarily synthesized in the intestines.  [10.]  ApoB100 is found on the surface of VLDL, IDL, LDL and Lp(a) particles; therefore, only ApoB100 particles are considered clinically relevant when assessing for cardiovascular disease risk.  Essentially, an ApoB blood test only measures particles containing ApoB100.  [2., 17.]

ApoB is considered a more sensitive marker for cardiovascular disease risk than LDL alone because there is one ApoB molecule on the surface of every potentially atherogenic particle: VLDL, IDL, LDL, and Lp(a).  Therefore, an ApoB measurement provides a direct count of the total number of potentially atherogenic particles, while a standard lipid panel can only calculate the number of LDL particles present.  [2.]

Elevated levels of ApoB are associated with an increased risk of cardiovascular diseases as well as increased likelihood of insulin resistance.  [14.]  Measuring ApoB levels can provide valuable information about an individual's cholesterol metabolism and their risk of developing heart disease. 

It is often used in conjunction with other lipid markers including a complete lipid panel and occasionally sdLDL (small dense LDL particles, which are more atherogenic than larger LDL particles) to assess cardiovascular risk and guide treatment decisions.  [6.] 

Function of ApoB in Lipid Metabolism and Cardiovascular Health

ApoB plays a pivotal role in lipid metabolism by facilitating the transportation of cholesterol and triglycerides through the bloodstream out to peripheral tissues. Its primary function is to act as a ligand for the cellular receptors responsible for the uptake of lipoprotein particles into peripheral tissues. 

Specifically, ApoB-100 binds to LDL receptors on the surface of cells, allowing for the internalization of LDL particles and the delivery of cholesterol to various tissues. However, dysregulation of ApoB levels can lead to the accumulation of LDL particles in the arterial walls, contributing to the development of atherosclerosis and cardiovascular disease.

Trapping of apoB particles in arterial walls initiates atherosclerosis, leading to complex lesions prone to plaque rupture and other cardiovascular events. ApoB concentration determines the number of trapped particles, influenced by size and arterial wall structure. 

This process deposits atherogenic cholesterol, compounded by variations in particle size and other proatherogenic factors. LDL-C and non-HDL-C are less accurate markers of cardiovascular risk compared to apoB, as recent data suggest similar risk between VLDL and LDL particles. ApoB integrates the atherogenic risk of both particle types, potentially enhancing clinical assessment and management of atherogenic dyslipoproteinemias.  [17.] 

Clinical Significance of ApoB Levels

Because one ApoB particle is present on the surface of every potentially atherogenic particle, a higher ApoB level indicates an increased risk of adverse cardiovascular events.  

ApoB Testing Options

Overview of ApoB Testing

ApoB testing involves assessing the levels of apolipoprotein B (ApoB) in the bloodstream, typically through blood serum or plasma samples.  Venipuncture is commonly required.

Preparation and Procedure for ApoB Testing

Preparation for ApoB testing does not require fasting, although other tests ordered in conjunction with ApoB levels may require fasting.  [17.]  Blood samples are collected via venipuncture and processed to separate serum or plasma.  They are then sent to a lab for analysis.

It is important to follow the test preparation instructions of the ordering healthcare provider.

Interpretation of ApoB Test Results

Normal Reference Range Values

The normal range for ApoB can vary slightly depending on the laboratory and the method used for testing. However, in general, the normal range for ApoB is considered to be between 60 and 120 mg/dL (milligrams per deciliter). It is important to note that these values may vary slightly between different laboratories and testing methods.  Also, ApoB levels tend to be higher in men than in women, and to increase with age.  [1.] 

Leading lipidologists and cardiovascular health experts point out that the Framingham Offspring Study demonstrates that an optimal ApoB level is below 80 mg/dL, especially in the setting of other risk factors for cardiovascular disease.  [1., 16.]

It is worth mentioning that ApoB levels are typically interpreted in conjunction with other lipid markers such as LDL cholesterol (LDL-C), triglycerides, total cholesterol, and possibly other specialized markers such as sdLDL. These markers provide a more comprehensive assessment of cardiovascular risk. 

ApoB levels should be interpreted by a healthcare professional or a functional medicine practitioner within the context of an individual's overall health and other risk factors. They can provide personalized recommendations and interventions to optimize cardiovascular health based on the ApoB levels and other relevant factors.

ApoB Levels Outside of the Reference Range

What Does High ApoB Indicate?

Because Apolipoprotein B (ApoB) is a component of the atherogenic lipid particles VLDL, IDL, LDL, and lipoprotein a [Lp(a)], it’s an effective marker to assess a person’s risk of developing coronary heart disease.  [13., 15.]

A high level of ApoB in the blood indicates an increased concentration of atherogenic particles. This is concerning because these particles are known to contribute to the development of atherosclerosis, a condition characterized by the buildup of plaque in the arteries, including the coronary arteries (the blood vessels around the heart). Atherosclerosis can lead to various cardiovascular diseases and events, including heart attacks and strokes.

Elevated ApoB is often associated with other risk factors for cardiovascular disease including high total cholesterol, LDL cholesterol, triglycerides and insulin resistance. It is considered a more accurate marker of cardiovascular risk than measuring LDL cholesterol alone.

To manage high ApoB levels, lifestyle modifications are typically recommended. This includes adopting a healthy diet low in saturated and trans fats, increasing physical activity, maintaining a healthy weight, and quitting smoking. In some cases, medication may be prescribed to help lower LDL cholesterol levels and reduce the risk of cardiovascular events.

Regular monitoring of ApoB levels through lab testing can help assess the effectiveness of interventions and guide treatment decisions. It is important to work with a healthcare professional to interpret the results and develop an appropriate plan for managing high ApoB levels.

What Does Low ApoB Indicate?

A low level of apoB in the blood indicates a decrease in the number of atherogenic particles present in the bloodstream.  This can have positive implications for cardiovascular health as atherogenic particles are associated with an increased risk of developing atherosclerosis and heart disease.

A low apoB level may be a result of various factors, including:

Lifestyle modifications: Adopting a healthy lifestyle, including regular exercise, a balanced diet, and weight management, can lead to a reduction in apoB levels.

Medications: Certain medications, such as statins, can lower apoB levels by reducing the production of LDL particles in the liver.

Genetic factors: Some individuals may have genetic variations that naturally result in lower apoB levels.

Dietary changes: Consuming a diet low in saturated and trans fats, and high in fiber and healthy fats (such as omega-3 fatty acids), can help lower apoB levels.

Low ApoB levels are protective against coronary artery disease.  In rare cases, levels below 40 mg/dL may indicate familial hypobetalipoproteinemia (a genetic deficiency of apolipoproteins, including ApoB) which may cause neurological or hepatic manifestations.  [19.]

It is important to note that while a low apoB level is generally considered beneficial for cardiovascular health, it should be interpreted in the context of other lipid markers and overall health status. Consulting with a healthcare professional such as a functional medicine practitioner can provide a comprehensive understanding of the individual's lipid profile and guide appropriate interventions if necessary.

Natural Ways to Optimize ApoB Levels

Dietary Strategies

Diets Containing Fermented Dairy Products: diets containing fermented dairy products have been shown to decrease the ApoB/ApoA1 ratio, a marker of cardiovascular disease risk.  [5., 9.]  

Foods Rich in Omega-3 Fatty Acids: Fatty fish (salmon, mackerel, sardines), flaxseeds, chia seeds, walnuts all have scientific evidence of efficacy in reducing ApoB/ApoA1 ratios and reducing cardiovascular disease risk.  [5., 9.]

Fiber-Rich Foods: Whole grains (oats, barley, quinoa), fruits (apples, berries, oranges), vegetables (broccoli, Brussels sprouts, carrots), legumes (beans, lentils) are all Mediterranean diet staples that have shown effectiveness in reducing cardiovascular disease risk.  [9.]

Avoid excess sugar: diets high in sugar are highly positively correlated with cardiovascular disease risk.  [5.]

Lifestyle Modifications

Regular Exercise: Aerobic activities (walking, jogging, swimming), strength training, yoga, tai chi may all promote cardiovascular health.  [5., 20.]

Smoking Cessation: Quitting smoking reduces oxidative stress and inflammation, contributing to improved lipid profiles.  [5.]

Stress Management: Techniques such as meditation, deep breathing exercises, yoga, and mindfulness may help lower stress levels and improve overall cardiovascular health,and in some cases may also have a positive effect on lipid profiles.  [12.]

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See References

[1.] Apolipoprotein B: Reference Range, Interpretation, Collection and Panels. eMedicine. Published online January 24, 2022. https://emedicine.medscape.com/article/2087335-overview# 

[2.] Behbodikhah J, Ahmed S, Elyasi A, Kasselman LJ, De Leon J, Glass AD, Reiss AB. Apolipoprotein B and Cardiovascular Disease: Biomarker and Potential Therapeutic Target. Metabolites. 2021 Oct 8;11(10):690. doi: 10.3390/metabo11100690. PMID: 34677405; PMCID: PMC8540246.

[3.] Brown WM, Chiacchia FS. Therapies to Increase ApoA-I and HDL-Cholesterol Levels. Drug Target Insights. 2008;3. doi:10.4137/DTI.S447

[4.] Florvall G, Basu S, Larsson A. Apolipoprotein A1 Is a Stronger Prognostic Marker Than Are HDL and LDL Cholesterol for Cardiovascular Disease and Mortality in Elderly Men. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2006;61(12):1262-1266. doi:https://doi.org/10.1093/gerona/61.12.1262 

[5.] Frondelius K, Borg M, Ericson U, Borné Y, Melander O, Sonestedt E. Lifestyle and Dietary Determinants of Serum Apolipoprotein A1 and Apolipoprotein B Concentrations: Cross-Sectional Analyses within a Swedish Cohort of 24,984 Individuals. Nutrients. 2017 Feb 28;9(3):211. doi: 10.3390/nu9030211. PMID: 28264492; PMCID: PMC5372874. 

[6.] Ito Y. [Apolipoprotein B and small, dense LDL-C]. Rinsho Byori. 2012 Apr;60(4):336-42. Japanese. PMID: 22686043.

[7.] Kuyl JM, Mendelsohn D. Observed relationship between ratios HDL-cholesterol/total cholesterol and apolipoprotein A1/apolipoprotein B. Clin Biochem. 1992 Oct;25(5):313-6. doi: 10.1016/0009-9120(92)80004-z. PMID: 1490290.

[8.] Morris G, Puri BK, Bortolasci CC, et al. The role of high-density lipoprotein cholesterol, apolipoprotein A and paraoxonase-1 in the pathophysiology of neuroprogressive disorders. Neuroscience & Biobehavioral Reviews. 2021;125:244-263. doi:https://doi.org/10.1016/j.neubiorev.2021.02.037 

[9.] Nacarelli GS, Fasolino T, Davis S. Dietary, macronutrient, micronutrient, and nutrigenetic factors impacting cardiovascular risk markers apolipoprotein B and apolipoprotein A1: a narrative review. Nutrition Reviews. Published online August 23, 2023:nuad102. doi:https://doi.org/10.1093/nutrit/nuad102 

[10.] Nakajima K, Nagamine T, Fujita MQ, Ai M, Tanaka A, Schaefer E. Apolipoprotein B-48: a unique marker of chylomicron metabolism. Adv Clin Chem. 2014;64:117-77. PMID: 24938018.

[11.] Nazir S, Jankowski V, Bender G, Zewinger S, Rye KA, van der Vorst EPC. Interaction between high-density lipoproteins and inflammation: Function matters more than concentration! Advanced Drug Delivery Reviews. 2020;159:94-119. doi:https://doi.org/10.1016/j.addr.2020.10.006

[12.] Papp ME, Lindfors P, Nygren-Bonnier M, Gullstrand L, Wändell PE. Effects of High-Intensity Hatha Yoga on Cardiovascular Fitness, Adipocytokines, and Apolipoproteins in Healthy Students: A Randomized Controlled Study. J Altern Complement Med. 2016 Jan;22(1):81-7. doi: 10.1089/acm.2015.0082. Epub 2015 Nov 13. Erratum in: J Altern Complement Med. 2017 May;23(5):396. PMID: 26565690; PMCID: PMC4739349.

[13.] Pencina MJ, D'Agostino RB, Zdrojewski T, Williams K, Thanassoulis G, Furberg CD, Peterson ED, Vasan RS, Sniderman AD. Apolipoprotein B improves risk assessment of future coronary heart disease in the Framingham Heart Study beyond LDL-C and non-HDL-C. Eur J Prev Cardiol. 2015 Oct;22(10):1321-7. doi: 10.1177/2047487315569411. Epub 2015 Jan 29. PMID: 25633587.

[14.] Purnell, J. Q., Kahn, S. E., Schwartz, R. S., & Brunzell, J. D. (2001). Relationship of Insulin Sensitivity and ApoB Levels to Intra-abdominal Fat in Subjects With Familial Combined Hyperlipidemia. Arteriosclerosis, Thrombosis, and Vascular Biology, 21(4), 567–572. https://doi.org/10.1161/01.atv.21.4.567

[15.] Richardson TG, Sanderson E, Palmer TM, Ala-Korpela M, Ference BA, Davey Smith G, et al. (2020) Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis. PLoS Med 17(3): e1003062. https://doi.org/10.1371/journal.pmed.1003062

[16.] Schaefer EJ, Tsunoda F, Diffenderfer M, et al. The Measurement of Lipids, Lipoproteins, Apolipoproteins, Fatty Acids, and Sterols, and Next Generation Sequencing for the Diagnosis and Treatment of Lipid Disorders. [Updated 2016 Mar 29]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK355892/

[17.] Sniderman AD, Thanassoulis G, Glavinovic T, Navar AM, Pencina M, Catapano A, Ference BA. Apolipoprotein B Particles and Cardiovascular Disease: A Narrative Review. JAMA Cardiol. 2019 Dec 1;4(12):1287-1295. doi: 10.1001/jamacardio.2019.3780. PMID: 31642874; PMCID: PMC7369156.

[18.] Thompson AG, Talbot K, Turner MR. Higher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2022 Jan;93(1):75-81. doi: 10.1136/jnnp-2021-327133. Epub 2021 Sep 13. PMID: 34518331; PMCID: PMC8685635. 

[19.] Welty FK. Hypobetalipoproteinemia and abetalipoproteinemia. Curr Opin Lipidol. 2014 Jun;25(3):161-8. doi: 10.1097/MOL.0000000000000072. PMID: 24751931; PMCID: PMC4465983. 

[20.] Yazdani R, Marefati H, Shahesmaeili A, Nakhaei S, Bagheri A, Dastoorpoor M. Effect of Aerobic Exercises on Serum Levels of Apolipoprotein A1 and Apolipoprotein B, and Their Ratio in Patients with Chronic Obstructive Pulmonary Disease. Tanaffos. 2018 Feb;17(2):82-89. PMID: 30627178; PMCID: PMC6320561.

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