Managing Blood Lipids and Lipoproteins
Deciding whether and how to treat elevated blood lipids hinges on a variety of factors, including overall cardiovascular risk and likelihood of adherence to dietary and lifestyle modification. People whose lipids are mildly elevated but are otherwise healthy may do well with dietary changes and initiation of an exercise regimen. On the other hand, people with high risk of cardiovascular disease (such as a history of cardiovascular events) may need to start on medication(s) in addition to changing their diet and exercising.
Dietary and Lifestyle Changes
Dietary modifications aim to reduce the intake and uptake of unhealthy fats such as saturated and trans fats and cholesterol from the diet. The inclusion of specific dietary compounds with cholesterol-lowering50 or cardioprotective properties may also reduce cardiovascular disease risk by several different mechanisms.
Diet is the most important aspect of a cholesterol management program. The American Heart Association and other experts recommend a diet that emphasizes51,52:
- Fruits and vegetables
- Whole grains
- Nuts and legumes
- Fish and skinless poultry, with limited amounts of red meat
- Non-tropical vegetable oils, such as olive, sunflower, safflower, canola, and other oils low in saturated fat. Note that the American Heart Association does not recommend deep frying foods regardless of the type of oil used. They also do not recommend coconut oil, which is high in saturated fat.
- Avoiding hydrogenated oils to reduce dietary trans fat
- Reducing added sugar and sodium
- Limiting daily alcohol consumption to no more than one drink for women and two drinks for men
In controlled clinical trials that replaced dietary saturated fat with polyunsaturated vegetable oils such as those listed above, cardiovascular disease was reduced by about 30%, which is roughly the degree of protection conferred by statin drugs. Substituting saturated fat for polyunsaturated vegetable oil lowers LDL cholesterol, which may in part explain the benefits observed. Observational trials have also found that higher intake of monounsaturated and polyunsaturated fats is associated with lower rates of death from cardiovascular disease or any cause. It should be noted that replacing saturated fat with refined carbohydrates and sugars has not been shown to reduce cardiovascular disease.53
Specific dietary approaches that are generally heart healthy are the Dietary Approaches to Stop Hypertension (DASH) diet and Mediterranean diet.
Caloric restriction is the reduction of dietary calories (by up to 40%) while still maintaining good nutrition.54 Restricting energy intake slows down the body’s growth processes, causing it instead to focus on protective repair mechanisms; the overall effect is an improvement in several measures of health. Observational studies have tracked the effects of caloric restriction on lean, healthy individuals, and demonstrated that moderate restriction (22‒30% decreases in caloric intake from normal levels) improves heart function and reduces markers of inflammation (C-reactive protein, tumor necrosis factor [TNF]), risk factors for cardiovascular disease (LDL cholesterol, triglycerides, blood pressure), and diabetes risk factors (fasting blood glucose, insulin levels).55-58 Preliminary results of the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) study, a long-term multicenter trial on the effects of calorie-restricted diets in healthy overweight volunteers,59 showed moderate calorie restriction can reduce several cardiovascular risk factors (LDL cholesterol, triglycerides, blood pressure, and C-reactive protein).60
More information is available in Life Extension's Caloric Restriction protocol.
Exercise is a fundamental component of any lipid management strategy. The American Heart Association and American College of Cardiology recommend adults engage in at least 150 minutes of moderate-intensity activity or 75 minutes of high-intensity activity each week for the prevention of cardiovascular disease.61 Exercise helps raise HDL levels and boost the efficiency of reverse cholesterol transport, the process by which cholesterol is carried from the blood vessels back to the liver for excretion.62 A small study published in 2019 found exercise had a greater effect on cholesterol synthesis than calorie restriction.63 Exercise reduces LDL significantly when combined with a heart-healthy diet—much more so than a healthy diet without exercise.64
A meta-analysis of 37 studies found that exercise usually resulted in moderate-to-strong improvements in levels of total cholesterol, LDLs, triglycerides, and HDLs. This same analysis also found that exercise consistently improved glucose and insulin levels, which are often elevated in people with an unhealthy lipid profile.65 Both aerobic and anaerobic exercise have beneficial effects on blood lipids, so an exercise regimen that combines strength training (eg, weightlifting) and endurance training (eg, running, swimming) is suggested.66
Medications to Manage Blood Lipids
Reduction of total cholesterol and LDL cholesterol (and/or triglycerides) by drugs usually involves inhibiting cholesterol production in the body or preventing the absorption/reabsorption of cholesterol from the gut. When the availability of cholesterol to cells is reduced, they are forced to pull cholesterol from the blood (which is contained in LDL particles). This has the net effect of lowering LDL cholesterol. Therapies that increase the breakdown of fatty acids in the liver or lower the amount of VLDL in the blood (like fibrate drugs or high-dose niacin)67 also result in lower serum cholesterol levels. Often, complementary strategies (eg, statin to lower cholesterol production plus a bile acid sequestrant to lower cholesterol absorption) are combined to meet cholesterol-lowering goals.
Decreasing cellular cholesterol production is the most common strategy for reducing cardiovascular disease risk, with HMG-CoA reductase inhibitors (statins) being the most commonly prescribed cholesterol-lowering treatments. Statins inhibit the activity of the enzyme HMG-CoA reductase, a key enzyme in cholesterol synthesis. Since cholesterol levels in cells are tightly controlled (cholesterol is critical to many cellular functions), the shutdown of cellular cholesterol synthesis causes the cell to respond by increasing the activity of the LDL receptor on the cell surface, which has the net effect of pulling LDL particles out of the bloodstream and into the cell. Statins may also reduce CHD risk by other mechanisms, such as reducing inflammation.68
Statins may induce serious side effects in some individuals, the most common being muscle pain or weakness (myopathy). The prevalence of myopathy is fairly low in clinical trials (1.5‒3.0%), but can be as high as 33% in community-based studies and may rise dramatically in statin users who are active (up to 75% in statin-treated athletes).69,70 Occasionally, statins may cause an elevation of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). These enzymes can be monitored by doing a routine chemistry panel blood test. Additionally, by inhibiting HMG-CoA reductase (an enzyme not only required for the production of cholesterol, but other metabolites as well), statins may reduce levels of the critically important antioxidant molecule CoQ10.
Targeting Cholesterol Absorption
Lowering cholesterol absorption from the intestines reduces LDL cholesterol in a different fashion; by preventing uptake of intestinal cholesterol, cells respond by making more LDL receptor, which pulls LDL particles out of the bloodstream. Ezetimibe (Zetia) and bile acid sequestrants (colesevelam [Welchol], cholestyramine [Prevalite, Questran], colestipol [Colestid]) are two classes of prescription treatment that work in this fashion. Ezetimibe acts on the cells lining the intestines (enterocytes) to reduce their ability to take up cholesterol from the intestines. Ezetimibe, when added to a statin, has been shown to reduce cardiovascular events in high-risk patients and has been recommended as an alternative treatment in those who cannot take statins.71 Bile acid sequestrants bind to bile acids in the intestine, which reduces their ability to emulsify fats and cholesterol. This has the net effect of preventing intestinal cholesterol absorption. Bile acid sequestrants may also increase HDL production in the liver, which is usually inhibited by the reabsorption of bile acids.72
The newest medications on the scene are agents that directly inhibit the enzyme PCSK9, effectively removing an inhibitor in the LDL receptor pathway. This means that more LDL receptors are free to grab LDL particles and remove them from the blood, thus potently lowering blood LDL concentrations. While highly effective in reducing LDL, the cost of PCSK9 inhibitors severely limits their use, but they are expected to become more affordable with time.73