Fats in us

As we age, we tend to have “high” in our blood — high blood pressure and high blood levels of glucose, lipids (such as, cholesterol and triglycerides), creatinine, uric acid, etc. Such symptoms are correlated with certain diseases (for e.g., diabetes, heart disease, kidney disease, arthritis, etc.) that are usually old age-related and/or genetically influenced disorders. I have a keener interest in cholesterol because some relatives, friends and I have experienced having blood cholesterol go up to an “unhealthy” level. For senior citizens like many of us, health and wellness is a hot topic when we talk to each other or when we get together.

Lipids and blood lipid profile

Lipids are waxy or fatty substances that are found in body cells. The major lipids include cholesterol and triglycerides. Cholesterol, a sterol or “modified steroid,” is a vital structural component that regulates fluidity and permeability of the cell membrane. It functions as material for the production of bile acids and bile salts that solubilize fats in the digestive tract, steroid hormones (adrenal gland hormones and sex hormones), and vitamin D. The myelin sheath that provides insulation for efficient conduction of impulses in nerve cells is rich in cholesterol. Thus, everything that cholesterol does is intentionally “good.” Triglyceride consists of three fatty acid units joined to one unit of glycerol. Triglycerides are the storage fats that are found in fat cells, such as those in adipose tissue. When the body needs an alternative food as energy source other than carbohydrates, the fat cells mobilize stored triglycerides to be used for our energy requirement.

Dietary cholesterol is in the form of either free cholesterol, or cholesteryl ester (cholesterol bonded to fatty acid) that is not readily absorbed and has to be broken down by an enzyme to cholesterol and fatty acid. The liver produces cholesterol from many foods, including those that are rich in carbohydrates and fats (triglycerides). The production of cholesterol requires acetylcoenzyme A, a metabolite derived mainly from carbohydrates and triglycerides. The rate-limiting enzyme that functions in the production of cholesterol is 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase.

Cholesterol and triglycerides circulate in blood plasma and constitute the blood lipids whose quantities are determined in clinical blood chemistry tests such as the lipid profile. These lipids are extremely insoluble in water and are carried in the bloodstream from the liver to various cells in the form of “fat balls” within lipid-binding proteins called lipoproteins. Proteins called apolipoproteins combine with lipids to form lipoproteins with different densities, such as chylomicron, very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). The less protein and more lipid there are in a lipoprotein, the less dense the lipoprotein is. The less dense a lipoprotein is, the bigger its size.

Normally, the LDL that carries cholesterol has apoB-100, protein that is recognized by the LDL receptor which is found on the surface of cells where cholesterol is needed. The LDL binds to the LDL receptor triggering endocytosis that brings the LDL and its associated receptor inside the cell. Cholesterol is released and the apoB-100 is degraded in the cell, while the LDL receptor is recycled to the cell surface. If more cholesterol is available than cells can use, they accumulate in blood LDL.

LDL and atherosclerosis; role of HDL

Different processes are widely believed to initiate the formation of plaque that is characteristic of atherosclerosis (hardening of artery wall), a risk factor in cardiovascular disease. These include: 1) oxidation of LDL particles that are retained in the artery wall, followed by modification of the protein component of LDL, resulting in loss of recognition by the LDL receptor (Berliner et al., Circulation 1995, vol. 91, pp. 2488-2496); and, 2) retention of LDL particles in the artery wall (which may be induced by cardiovascular risk factors, such as, smoking, diabetes, hypercholesterolemia, hypertension and age), leading to cell injury and inflammation (Stocker & Keaney, Physiological Reviews 2004, vol. 84, pp. 1381–1478). Apparently, the amount of cholesterol that is carried by LDL particles is not implicated as a triggering factor in each case. The LDL particles vary in structures and give rise to two forms: LDL pattern A (with predominantly large buoyant particles) and LDL pattern B (with predominantly small dense particles). The small dense LDL particles are preferentially retained in the artery wall and are believed to have a role in atherosclerosis. LDL pattern B usually correlates with high level of triglycerides and low level of HDL.

Excess cholesterol can be removed from cells in the artery wall by HDL and carried back to the liver in a process called reverse cholesterol transport. The HDL receptor that is present on the liver cell surface binds the apoA-1 (protein) of HDL and plays a crucial role in regulating cholesterol level. The quality of HDL receptor determines how efficiently excess cholesterol can be removed from blood. The liver converts cholesterol to bile salts or excretes it in bile into the digestive tract. A portion of the excreted cholesterol is eliminated through the feces, while another portion is recycled; that is, reabsorbed in the small intestine and brought back into the bloodstream.  

Counting the blood lipids

The levels of blood cholesterol and triglycerides are expressed in either mass or mole count per unit volume of blood. Mass and mole count are given in milligrams (mg) and millimoles (mmol), respectively. The unit of volume is either deciliter (dL) or liter (L). The world standard unit which is designated as Systeme International (SI) unit is millimoles per liter (mmol/L). “World standard” is not universal as some countries use milligrams per deciliter (mg/dL) which is the traditional unit. Some scientific journals preferably use mmol/L as the unit but also give the value in mg/dL, considering the large base of healthcare providers and researchers who are used to mg/dL. For LDL, HDL or total cholesterol, mmol/L is converted to mg/dL by multiplying the value in mmol/L by 39. For triglycerides, mmol/L is changed to mg/dL by multiplying the value in mmol/L by 89. The factor is specific for cholesterol or triglyceride because it depends on the molecular weight (or molar mass) of the substance.

The total cholesterol (in mmol/L) is roughly the sum of HDL cholesterol, LDL cholesterol and 45 percent of triglycerides (also referred to as VLDL triglycerides), assuming a fasting state of about 12 hours. When using mg/dL, the level of triglycerides is multiplied by 20 percent instead of 45 percent. LDL cholesterol is not directly measured but it is estimated using the Friedewald equation, by subtracting from total cholesterol the HDL cholesterol and 45 percent (or 20 percent) of triglycerides, depending on the unit. This equation has limitations when used with high levels of total cholesterol and triglycerides, and has a correction factor. In some laboratories, the lipoprotein profile which shows whether an individual has LDL pattern A or pattern B is done but it costs much more than the lipid profile.

Targets in lowering blood lipids

Omega-3 fatty acids are polyunsaturated fatty acids. They include alpha-linolenic acid (ALA) which can be obtained from green leafy vegetables (e.g. malunggay, spinach), vegetable oils (e.g., canola oil, soybean oil), nuts (e.g., walnuts, peanuts) and seeds (e.g. flax seeds, pumpkin seeds), and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that can be obtained from fish (e.g., sardines, tuna, mackerel, salmon). Omega-3 fatty acids are known to lower the level of triglycerides in the blood.

Plant sterols called phytosterols (e.g., beta-sitosterol) are chemically similar to cholesterol. They can be obtained from nuts, seeds, legumes, whole grains, vegetables and fruits. The cholesterol-lowering capacity of phytosterols is due to increased production of the sterol transporter in the intestine, enhancing excretion of sterols including cholesterol and elimination through the feces.

Medicine, such as statins and ezetimibe, among others, are in clinical use. The action of statin is due to the inhibition of HMG-CoA reductase, the enzyme used in the production of cholesterol in the liver. The inhibition leads to increased production of LDL receptor, promoting removal of cholesterol from blood. Ezetimibe which is used either alone or in combination with another drug, such as a statin, works by reducing the amount of cholesterol absorbed in the intestine, enhancing excretion.

Whatever the approach is in lowering blood cholesterol to a desirable “healthy” level, we must note that cholesterol is an essential substance for the maintenance of cellular functions. High levels of triglycerides and LDL cholesterol and a low level of HDL cholesterol can contribute to atherosclerosis. It must be noted though that the size of the LDL particles, rather than the amount of cholesterol carried by LDL particles, is the triggering factor in the development of plaque. More cholesterol can be potentially removed when the HDL level is high, thus a high HDL cholesterol level is correlated with a low risk for atherosclerosis. On the other hand, low LDL and HDL cholesterol levels can be disastrous to the cells in general. If not carefully monitored, the use of cholesterol-lowering medications may lead to the lowering of total blood cholesterol to an unhealthy and detrimental level. Persons who are taking cholesterol-lowering medicines should be aware and cautious of possible side effects.

Some people have a genetic predisposition to familial hypercholesterolemia and develop severe atherosclerosis at a young age. In those individuals, the LDL receptor is defective and the cell’s receptor-mediated uptake of cholesterol from LDL is blocked. Those people need a suitable and regulated medical treatment. 

Lifestyle changes, such as quitting smoking, limiting intake of alcoholic beverages, getting enough sleep, and other activities that can minimize oxidative stress are beneficial. Proper nutrition and strenuous physical activities for weight reduction and body sustenance are helpful for most people with high levels of triglycerides and LDL cholesterol in the blood.

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Elsie C. Jimenez, a biochemist and molecular biologist, is professor emeritus at the University of the Philippines Baguio. She can be contacted at [email protected].