With the rise in the prevalence of chronic diseases, majorly driven by the rise in obesity, the world is getting to know more about weight management strategies. The goal of weight management is to maintain the body mass index (BMI) in the normal range of between 18.5 and 24.9. BMI is defined as the ratio of weight (measured in kilograms) to height (measured in square meters). The BMI categories ranges from underweight to obese. The ideal BMI lies within the normal range at which point the risk for chronic diseases is presumed to be reduced. Given that adults’ height cannot be manipulated, to achieve and maintain a normal BMI requires weight management.
Information on weight management strategies is widely available. The most common ways of attaining and maintaining a healthy weight include using medication, surgery, diet modification and engaging in regular physical activities. Even though most clinicians recommend a combination of weight management strategies, majority of individuals perceive medication as the easiest strategy. Statins are the most prescribed medications for weight management. Statins work by inhibiting cholesterol synthesis in the liver. Cholesterol is the major player in obesity. It belongs to a class of lipids called sterols. Exogenous sources of sterols are derived from foods of plant (phystosterols) and animal (cholesterol) foods.
However, in additional to dietary sources, the liver endogenously makes a considerable amount of cholesterol. Cholesterol is needed for energy production, cushioning of vital organs, manufacture of steroid hormones and coenzyme Q synthesis. However, excessive intake of cholesterol mostly from fatty foods creates a need for inhibiting endogenous cholesterol synthesis. Statins inhibit the enzyme 3-Hydroxy-3-Methylglutaryl Coenzyme A reductase (HMGCR) that is important in liver cholesterol synthesis. Inhibiting HMGCR inhibits liver cholesterol synthesis. Once the body signals reduced levels of cholesterol, LDL receptors are upregulated in order to increase cholesterol uptake from circulation thus lowering cholesterol even further. Unfortunately, inhibiting HMGCR also inhibits the synthesis of other products that are derived from cholesterol. These include ubiquinones (Coenzyme Q-10), dolichols and isoprenylated proteins that are involved in cellular respiration and muscle cell functioning as well as steroid hormones. As statins inhibit formation of these other products, it is likely that the side effects of statins arise from this cause.
Besides statins, bile acid-binding drugs like cholestyramine bind bile and enable its excretion in feces. Since bile is made from cholesterol, the liver will be triggered to make more bile using cholesterol and hence further reducing serum cholesterol levels.
Even with statin use to inhibit cholesterol synthesis, the diet may contain considerable amounts of saturated fats as well as trans fats that are responsible for obesity and chronic diseases. Use of statins and cholestylramine thus requires moderated intake of saturated fats and trans fats. In addition to diet modification and medication use, regular physical exercises helps to increase the number of good cholesterol carriers (High density lipoproteins also known as HDL). These carriers are involved in reverse cholesterol transport where they transport excess cholesterol from cells to the LDL-receptors located on the liver. The liver then uses the excess cholesterol to make bile that is used to emulsify lipids or excreted in feces. Without physical exercise, the body cannot have enough HDL cholesterol and hence cholesterol would accumulate around body organs and in adipose tissue, ultimately increasing the risk of obesity and chronic diseases. Therefore, besides monitoring the diet, it is important to engage in regular physical activity.
Regular medical check-up is highly recommended. It is common practice to not know the body lipid profiles and recommended cut-off values for major health players until when presented with a medical scare. Current research shows that one should not only focus on cut off values for lipid carriers but also on the size of the carries (especially LDL and HDL values). Low density lipoproteins (LDL) are involved in transporting cholesterol from the liver to the tissues. In addition to lipid profiles and cut-off values, the size of the lipoproteins especially LDL and HDL determines health. Research shows that increasing triglyceride intake (dietary fats) leads to production of small dense LDL whereas decreasing triglycerides leads to an increase in the light and fluffy LDL (Austin et al, Circulation 1990; 82:495). It is the small and dense LDL particles (also known as phenotype B) that are mostly associated with increased incidence of cardiovascular diseases.
Atherosclerosis characterized by the accumulation of fatty materials in the inner walls of blood vessels is largely driven by the degeneration (oxidation) of lipids which infiltrate the blood vessel and cause inflammation. Large LDL’s are not oxidized easily, are less likely to slip through a blood vessel tear and have a longer longevity. Without oxidation, LDL cholesterol is less likely to lead to any diseases. It is assumed that the low levels of small LDL and high levels of HDL are responsible for low incidences of cardiovascular diseases in Japanese. Rats also have a natural resistance to atherosclerosis because HDL is the major cholesterol carrier.
In conclusion, to reduce the risk of chronic diseases, it is highly recommended to have improved diet, active lifestyle and regular medical checkups. Medically, a combination of cholesterol synthesis inhibitors as well as bile binding drugs is being studied.
