Cholesterol, an animal sterol, is a waxy substance found in every cell in our body. Cholesterol is used as a base for the production of steroid hormones, bile salts, and vitamin D as well as maintaining cell membrane fluidity. Without cholesterol we would not be able to properly digest foods, our cell structure would not be able to withstand any changes in temperature, and a significant number of important hormones such as estrogen, and testosterone could not be produced.
Our cholesterol is produced in the liver, from the molecule acetyl-coenzyme-A, through a number of complicated reactions that I won’t bore you with. A key step is a conversion that is controlled by the enzyme HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase. This enzyme can block the production of cholesterol making it an important target for cholesterol lowering drugs called statins, but it also controls the production of many other molecules such as co-enzyme-q10. That's why there are so many side effects of taking these drugs. Nearly 10-12% of patients on statin drugs will experience statin induced muscle pain. Other potential adverse reactions to statin drug use include elevated liver enzymes, lung disease, and in a small subset of patients can even increase risk for Type 2 Diabetes Mellitus.
But back to cholesterol synthesis. The majority of cholesterol is synthesized, recycled, and degraded in the liver. So how does the water fearing cholesterol molecules that you eat get to the liver from the gut? And then how does it go from the liver to the cells if it cannot travel through the bloodstream alone?
Well, first cholesterol molecules are transported to the liver via the lymph in complexes called chylomicrons. When it gets to the liver it is repackaged and the cholesterol is “chaperoned” around the body by the lipoprotein complexes. There are a number of lipoprotein complexes, which are classified based on the ratio of proteins to fat and cholesterol. Think of these as cholesterol carriages, moving it all around the body. LDL takes the cholesterol to tissues and HDL brings cholesterol back to the liver when we have too much. Low density lipoproteins (LDL), very low density lipoproteins (vLDL) and chylomicrons all have very high fat and cholesterol content as compared with the protein rich high density lipoprotein (HDL). Once packaged into vLDL, the cholesterol enters circulation and some of the cholesterol is deposited to the tissues along with fatty acids. Once it drops the cholesterol off, the LDL complexes should be taken up by liver cells after attaching to the LDL receptor on their surface. Meanwhile, HDL scavenges blood vessels and tissues for free-form excess cholesterol. It then returns to the liver where cholesterol can be excreted through the bile or recycled.
Cholesterol and Cardiovascular Health
High cholesterol, triglycerides, LDL, and trans fats are linked to increased risk of cardiovascular events such as heart attacks and strokes. Cholesterol can build up due to increased production, increased consumption, or decreased excretion. The cause of the build-up as well as the form of cholesterol in the plasma is important when determining risk and treatment.
Genetic disorders can affect the LDL receptors in the surface of liver cells causing an increased amount of LDL in circulation. High LDL levels in circulation lead to an increased risk of cardiovascular events irrespective of diet and lifestyle in these patients. However, genetic causes affect a small percent of the population diagnosed with high cholesterol. The majority of cases in North America can be linked to diet and lifestyle.
Increased consumption of cholesterol rich foods result in increased levels of LDL in circulation. Excess LDL-C can attach onto and infiltrate the walls of blood vessels. When the LDL infiltrates it will form a reactive oxidative species that will attract immune cells. From the complexes formed, more white blood cells will congregate and an inflammatory cascade will be initiated. As more and more cells are attracted to this middle layer of a blood vessel, the plaque will begin to disrupt blood flow and may eventually fully block the vessel, or a piece of the plaque can rupture and travel around the body. All of these scenarios can have very serious consequences.
The “arthrogenic triad” are lab findings that show an increased risk for the development of atherosclerosis (or hardening of arteries) this includes high serum LDL, low HDL and high triglycerides. Risks are increased with low fiber diets as this prevents the excretion of cholesterol. A somewhat inactive lifestyle can also increase the risk of the LDL adhering to the vessels.
Managing Healthy Cholesterol Levels
A clinical anomaly whereby patients who exhibited high total cholesterol lab findings, with no increased risk for cardiovascular events, had scientists re-examining all of the “players” involved in cholesterol transport. HDL is able to scavenge for excess cholesterol in tissues and in circulation to take back to the liver for excretion. As such it is an important target for treatment. Certain types of fats in the diet can promote HDL, while saturated and trans-fats increase the LDL content.
How do you increase HDL? Well luckily that can be done by eating enough good fats. We discussed what makes a good fat in our post earlier this week, explaining how good fats are unsaturated, non-trans, with one or more double bond present, like olive or fish oils.
HDL can also be increased by eating the citrus fruit called "bergamot" (often added to earl grey tea). Some very interesting research, including a number of human clinical studies, have been done to understand the effects of supplementation with a standardized bergamot extract on various cholesterol parameters. Multiple studies have focused on bergamots effects on total cholesterol, LDL, triglycerides, blood sugar, and markers of oxidative stress with all showing clinically significant reduction with an increase in HDL. It has been shown to be useful in high cholesterol patients, those with fatty liver disease, metabolic syndrome and in conjunction with statin drugs. All of this research is pretty compelling for bergamot supplementation since it reduces “bad” cholesterol (LDL) and improves your “good” cholesterol (HDL). AOR's Opti Cholest contains 100omg of a standardised bergamot extract for cardiovascular health per capsule.
So now that you know how cholesterol works in the body we can make sure we are getting the right kind delivered in the right way.
Adams SP, Sekhon SS, Wright JM. Lipid-lowering efficacy of rosuvastatin. Cochrane Database Syst Rev. 2014 Nov 21;(11):CD010254. doi: 10.1002/14651858.CD010254.pub2.
Babish JG, Dahlberg CJ, Ou JJ, Keller WJ, Gao W, Kaadige MR, Brabazon H, Lamb J, Soudah HC, Kou X, Zhang Z, Pacioretty LM, Tripp ML. Synergistic in vitro antioxidant activity and observational clinical trial of F105, a phytochemical formulation including Citrus bergamia, in subjects with moderate cardiometabolic risk factors .Can J Physiol Pharmacol. 2016 May 31:1-10.
Cappello AR, Dolce V, Iacopetta D, Martello M, Fiorillo M, Curcio R, Muto L, Dhanyalayam D. Bergamot (Citrus bergamia Risso) Flavonoids and Their Potential Benefits in Human Hyperlipidemia and Atherosclerosis: an Overview.Mini Rev Med Chem. 2016;16(8):619-29.
Giglio RV, Patti AM, Nikolic D, Li Volti G, Al-Rasadi K, Katsiki N, Mikhailidis DP, Montalto G, Ivanova E, Orekhov AN, Rizzo M. The effect of bergamot on dyslipidemia. Phytomedicine. 2015 Dec 30. pii: S0944-7113(15)00378-5. doi: 10.1016/j.phymed.2015.12.005. [Epub ahead of print]
Gliozzi M, Walker R, Muscoli S, Vitale C, Gratteri S, Carresi C, Musolino V, Russo V, Janda E, Ragusa S, Aloe A, Palma E, Muscoli C, Romeo F, Mollace V. Bergamot polyphenolic fraction enhances rosuvastatin-induced effect on LDL-cholesterol, LOX-1 expression and protein kinase B phosphorylation in patients with hyperlipidemia. Int J Cardiol. 2013 Dec 10;170(2):140-5. doi: 10.1016/j.ijcard.2013.08.125. Epub 2013 Sep 8.
Gliozzi, M, Carresi C, Musolino, V, Palma, E, Muscoli, C, Vitale C, Gratteri, S.et al. The effect of bergamot-derived polyphenolic fraction on LDL small dense particles and non alcoholic fatty liver disease in patients with metabolic syndrome. Advances in Biological Chemistry 4, no. 02 (2014): 129.
Mollace V, Sacco I, Janda E, Malara C, Ventrice D, Colica C, Visalli V, Muscoli S, Ragusa S, Muscoli C, Rotiroti D, Romeo F. Hypolipemic and hypoglycaemic activity of bergamot polyphenols: from animal models to human studies. Fitoterapia. 2011 Apr;82(3):309-16. doi: 10.1016/j.fitote.2010.10.014. Epub 2010 Nov 4.
Mora S, Glynn RJ, Ridker PM .High-density lipoprotein cholesterol, size, particle number, and residual vascular risk after potent statin therapy. Circulation. 2013 Sep 10;128(11):1189-97. doi: 10.1161/CIRCULATIONAHA.113.002671. Epub 2013 Sep 3.
Toth PP, Patti AM, Nikolic D, Giglio RV, Castellino G, Biancucci T, Geraci F, David S, Montalto G, Rizvi A, Rizzo M. Bergamot Reduces Plasma Lipids, Atherogenic Small Dense LDL, and Subclinical Atherosclerosis in Subjects with Moderate Hypercholesterolemia: A 6 Months Prospective Study. Front Pharmacol. 2016 Jan 6;6:299. doi: 10.3389/fphar.2015.00299. eCollection 2015.