Cholesterol

Introduction

    The first topic I am going to cover in this blog is cholesterol. It seems to be a buzz word in nutrition circles. What makes cholesterol “good” or “bad”? What are the biochemical pathways for cholesterol in the body? And what are cholesterol’s implications for disease and health? These are the questions I will attempt to answer and discuss. We just finished our cardio-pulm unit in medical school, and I’m on spring break right now, so it is fresh on my mind. I will first explain the biochemistry of cholesterol and then its applications. Since the biochemistry of cholesterol is probably the most interesting thing you will learn all week, you should read it in its entirety. But, if your eyes glaze over, I will understand if you skip ahead. 

Biochemistry of Cholesterol

    Cholesterol is a type of lipid, or fat, meaning that it does not mix well in water. Its chemical properties make it essential to many processes in the body and a key component in each cell’s membrane. Additionally, it is a precursor to hormones like cortisol, testosterone, and estrogen. While cholesterol on a food label may have a negative connotation, it is an essential nutrient.

    There are two ways that we can get cholesterol: cells can make it or it can be obtained through food. When cholesterol is obtained from the diet, mainly by consuming animal products, it is transported to the liver to be processed further. The liver packages cholesterol into microscopic droplets called vesicles. The vesicles are loaded with cholesterol and triglycerides that will be transported through the blood to various tissues throughout the body, like the heart, adipose (fat storage), and muscles. There are also special proteins on the vesicles called Apo proteins, and they give unique properties to the cholesterol-containing vesicles that the liver sends out.

    The first type of vesicle is called VLDL, which stands for very-low-density-lipoprotein. It has very low density because it contains very high amounts of triglycerides and cholesterol and less protein; “about 90% lipids and 10% protein, with 70% of the lipids being triglycerides” [1]. One of the special Apo proteins on VLDL is ApoC, which allows it to deliver triglycerides to tissues throughout the body. As triglycerides are delivered to the body, VLDL’s density increases and it eventually becomes LDL. 

    The 1985 Nobel Prize in medicine was awarded to Michael Brown and Joseph Goldstein for their work on the infamous LDL receptor. The LDL receptor is located on cells throughout the body, and it specifically recognizes an Apo protein called ApoB100. When an LDL particle containing ApoB100 passes by an LDL receptor, the LDL receptor-containing cell engulfs the entire LDL particle. This is how cells throughout the body take up cholesterol, and it is a normal and good process. 

    The problem with LDL, often termed “bad” cholesterol, comes when it hangs around in the blood for too long. When this happens, LDL becomes oxidized. Simply put, LDL is bad when it is in too high concentrations in the blood for too long. This can eventually contribute to the formation of atherosclerosis, which leads to a whole host of cardiovascular problems. 

    HDL, on the other hand, refers to high-density lipoprotein. Why does it have a higher density? This is because HDL contains more protein relative to lipids. HDL is often referred to as “good” cholesterol because it can absorb cholesterol from tissues and bring it back to the liver, where it can then be excreted in the stool.

Atherosclerosis

Atherosclerosis begins when the inner lining of blood vessels, called the endothelium, is damaged. This can be caused by many things, such as high blood pressure, high sugar in the blood (as indicated by a high A1C), and toxins like those from cigarette smoke [2]. Oxidized LDL particles become trapped beneath the damaged endothelium, which causes an inflammatory response. This sends a signal to a special type of cell called a macrophage. You can picture macrophages as Pac-Man-resembling cells (yes, Pac-Man from arcade games) that eat the oxidized LDL. When the macrophages become engorged with oxidized LDL, they become foam cells. The foam cells then die and a fibrous cap is placed on top of them. This is now referred to as plaque in the arteries. 

Image credit: https://en.wikipedia.org/wiki/Low-density_lipoprotein


Ideal Cholesterol Levels

There is some disagreement about what is considered ideal cholesterol levels in the blood. Having too high cholesterol (hypercholesterolemia), is not in and of itself a medical condition, but it can be a contributing factor to cardiovascular diseases, like heart attacks, strokes, heart failure, and others related to atherosclerosis. It is very important to note that there are lots of other factors that play into one’s risk of developing cardiovascular diseases. These include smoking, genetic predisposition, diabetes, and high blood sugar.  the generally accepted ranges for cholesterol according to Johns Hopkins Medicine [3]. 

Just to be clear, lowering the risk of cardiovascular disease involves lowering total cholesterol, lowering LDL [4], and increasing HDL. Additionally, you want to lower triglyceride levels. (Triglycerides are another type of fat transported in the blood. Maybe I will discuss these more in another post.)


Total cholesterol ranges:

  • Normal: Less than 200 mg/dL
  • Borderline high: 200 to 239 mg/dL
  • High: At or above 240 mg/dL


LDL ranges:

  • Optimal: less than 100 mg/dL
  • Near-optimal: 100 to 129 mg/dL
  • Borderline high: 130 to 159 mg/dL
  • High: 160 to 189 mg/dL
  • Very high: 190 mg/dL and higher


HDL ranges:

  • Normal: greater than 40 mg/dL


Triglyceride ranges:

  • Healthy: less than 150 mg/dL


Improving Cholesterol

What can be done to improve cholesterol levels? Here are some general recommendations:

  • Reduce saturated fat intake and eliminate trans fats: Studies have shown that dietary saturated fat blocks LDL receptors and increases LDL levels in the blood [5]. Trans fats raise overall cholesterol levels.
  • Consume more soluble fiber: Soluble fiber reduces the amount of cholesterol that is absorbed in the intestines and can lower overall cholesterol levels. Foods high in soluble fiber include beans, fruits, vegetables, whole grains, nuts, and seeds.
  • Exercise: According to recommendations by the ACC and AHA, “Adults should engage in at least 150 minutes per week of accumulated moderate-intensity physical activity or 75 minutes per week of vigorous-intensity physical activity” to reduce [6].
  • Avoid smoking and heavy alcohol intake: Studies have repeatedly shown that any tobacco consumption and excessive alcohol consumption worsen cholesterol levels. Being a member of the Church of Jesus Christ of Latter-day Saints, I think it is neat that the health code called the Word of Wisdom that was given through revelation to the prophet Joseph Smith specifically prohibits the consumption of tobacco and alcohol. 
  • Medications: I won’t dive into all the medications that reduce circulating cholesterol, but I will mention two of the most common types. 
    • Statins: These lower cholesterol in the blood by blocking an enzyme that makes cholesterol. Because cells cannot make their own cholesterol, they make more LDL receptors and take more LDL out of the blood.
    • Ezetimibe: This type of medication blocks cholesterol from being absorbed in the intestines.


Other Notes

  • Whey protein supplementation: Some studies suggest that whey protein supplementation can help lower total cholesterol levels, but the results are mixed. A meta-analysis of 13 studies showed that there was no significant effect of whey protein supplementation on total cholesterol. However, it did show that whey protein supplementation had some benefit in lowering triglycerides. [7] 
  • Omega-3 fatty acids: Studies have shown that consuming foods rich in omega-3 fatty acids, like fish, will help lower the triglycerides in the blood without affecting cholesterol levels. [8]
  • Refined sugar is one of my favorite culprits. I reviewed several studies on its relationship to cholesterol and found mixed results. Unfortunately, specific nutrition science tends to be this way, and you can pretty much find some study out there to affirm whatever you want to believe. That is why it is important to look at the details of a study, such as its methods, sample size, funding and whether other studies have similar findings. For now, I will say that refined sugar overconsumption is generally bad, but its effect on cholesterol is something I will need to research further. 

Conclusion

Cholesterol is an essential nutrient, and maintaining optimal levels of the various circulating cholesterol-containing vesicles is important in reducing the risk of developing cardiovascular disease. LDL cholesterol, when elevated, contributes to the formation of plaque in the arteries and HDL cholesterol can help combat LDL’s effects. Taking active steps to improve cholesterol levels can reduce the risk of having adverse cardiovascular events and improve one’s quality of life. 



Sources

  1. Juarez Casso FM, Farzam K. Biochemistry, Very Low Density Lipoprotein. [Updated 2022 Dec 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK587400/
  2. Gimbrone, M. A., Jr, & García-Cardeña, G. (2016). Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circulation research, 118(4), 620–636. https://doi.org/10.1161/CIRCRESAHA.115.306301
  3. Johns Hopkins Medicine. (n.d.). Lipid panel. Retrieved from https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/lipid-panel#:~:text=These%20are%20the%20adult%20ranges,130%20to%20159%20mg%2FdL
  4. Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent, C., Blackwell, L., Emberson, J., Holland, L. E., Reith, C., Bhala, N., Peto, R., Barnes, E. H., Keech, A., Simes, J., & Collins, R. (2010). Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet (London, England), 376(9753), 1670–1681. https://doi.org/10.1016/S0140-6736(10)61350-5
  5. Siri-Tarino, P. W., Sun, Q., Hu, F. B., & Krauss, R. M. (2010). Saturated fatty acids and risk of coronary heart disease: modulation by replacement nutrients. Current atherosclerosis reports, 12(6), 384–390. https://doi.org/10.1007/s11883-010-0131-6
  6. Arnett, D. K., Blumenthal, R. S., Albert, M. A., Buroker, A. B., Goldberger, Z. D., Hahn, E. J., Himmelfarb, C. D., Khera, A., Lloyd-Jones, D., McEvoy, J. W., Michos, E. D., Miedema, M. D., Muñoz, D., Smith, S. C., Jr, Virani, S. S., Williams, K. A., Sr, Yeboah, J., & Ziaeian, B. (2019). 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation, 140(11), e563–e595. https://doi.org/10.1161/CIR.0000000000000677
  7. Zhang, J. W., Tong, X., Wan, Z., Wang, Y., Qin, L. Q., & Szeto, I. M. (2016). Effect of whey protein on blood lipid profiles: a meta-analysis of randomized controlled trials. European journal of clinical nutrition, 70(8), 879–885. https://doi.org/10.1038/ejcn.2016.39
  8. Goh, Y. K., Jumpsen, J. A., Ryan, E. A., & Clandinin, M. T. (1997). Effect of omega 3 fatty acid on plasma lipids, cholesterol and lipoprotein fatty acid content in NIDDM patients. Diabetologia, 40(1), 45–52. https://doi.org/10.1007/s001250050641

Comments

  1. Laura Lee AndersenApril 10, 2024 at 7:23 AM

    Great Info! Thank you Ethan. Unfortunately what sugar does to a person isn't so Sweet!

    ReplyDelete

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