Having high blood levels of the bad LDL cholesterol (>100 mg/dL) is associated with increased risk for heart attacks and premature death, and is the single most important predictor of forming plaques in your arteries. The American Heart Association, American College of Cardiology, and many other experts recommend lowering elevated LDL levels to 70 mg/dL in people who are at increased risk for heart attacks (Circulation, 2016;133(18):1795–1806). However, some patients still suffer heart attacks at LDL levels of 70 mg/dL. New combinations of drugs can lower LDL cholesterol below 15 mg/dL, and an excellent and comprehensive review of these studies shows that the lower the LDL cholesterol, the less likely a person is to suffer a heart attack (J of Lipids, Apr 23, 2018). People with a genetic deficiency of a chemical called PCSK9 have LDL levels of 15 mg/dL and do not appear to suffer from heart attacks from these extremely low levels (J of Lipid Res, 2009;50:S172–S177).
• A study of more than 15,000 patients treated for six years with drugs to lower LDL below 30 mg/dL after they suffered a heart attack, had lower death rates and fewer repeat heart attacks than similar patients treated to LDL cholesterol levels of 70 mg/dL (AMA Cardiol, 2017;2(5):547-555). Statins were used to reduce the amount of LDL made by the liver, ezetimibe (Zetia) to reduce LDL cholesterol absorption from the intestine, and/or PCSK9 inhibitors to drive cholesterol from the bloodstream into the liver. The researchers reported no increased risk for muscle aches, liver damage, diabetes, cancer, or bleeding strokes.
• The JUPITER trial found that getting blood levels of LDL cholesterol below 50 mg/dL reduced heart attack rate by more than 65 percent and death rate by 44 percent. However, it increased risk for diabetes, liver diseases, and insomnia (J American Coll of Card, 2011;57(16):1666–1675).
• Another review article showed that to prevent heart attacks, LDL cholesterol should be as low as possible (J Intern Med, Jun 2017;281(6):534-553).

Studies Raising Concerns About Very Low LDL Cholesterol Levels
Today we have several powerful drugs that can lower the bad LDL cholesterol below 15 mg/dL and doctors don’t know if it is safe to do this. Several articles have shown that having very low levels of the bad LDL cholesterol may be associated with increased risk for cancer, strokes, depression, anxiety and premature death:
• The Helsinki Businessmen Study showed that people who have reduced ability to absorb cholesterol from the food that they eat and therefore have low blood total and LDL cholesterol levels are at increased risk for an early death, especially in men over 75 years of age (J Amer Ger Soc, Jan 17, 2020;68(2)).
• Post-menopausal women, 68 to 71 years of age, who had higher LDL cholesterol levels were far more likely to live to age 90 than those with lower levels (J Amer Ger Society, January 17, 2020).
• Researchers followed close to 100,000 men and women yearly for nine years and found that those who had levels of LDL cholesterol below 70 were at significantly increased risk for suffering a stroke and the lower the level of LDL, the higher the risk (Neurology, July 2, 2019;93(5)).
• A study of 27,937 women followed for more than 19 years found that those with LDL levels below 70 were more than twice as likely to suffer hemorrhagic strokes as those with normal levels (Neurology, May 07, 2019; 92 (19)).
• People who have non-genetic low LDL cholesterol levels are at increased risk for cancer (J Natl Cancer Inst, Mar 16, 2011;103(6):508-19).
• A study from Duke University showed that people with low blood levels of cholesterol are at increased risk for being depressed and suffering from anxiety (Psychosom Med, May-Jun, 1999;61(3):273-9). Low levels of cholesterol may damage your brain because your body makes several hormones and vitamin D from cholesterol that are necessary for healthy cell growth, and lack of vitamin D can interfere with the growth of new nerves.
• Pregnant women with low LDL cholesterol levels appear to be at increased risk for premature birth and giving birth to very small babies (Pediatrics, Oct 1, 2015).

It is usually safe to lower cholesterol with diet, exercise and some medications, but if your cholesterol drops for no obvious reason, you may be in trouble. You may not be able to absorb certain nutrients, you may have liver damage and not be able to make cholesterol, or you may have a serious disease that damages normal body functions. Both high and low cholesterol can cause depression.

Drugs Used to Lower the Bad LDL Cholesterol
Statins block the enzyme that your liver uses to make cholesterol. They can cause or increase risk for liver damage, muscle pain and diabetes.
Ezetimibe (Zetia) prevents absorption of cholesterol in bile acids in the small intestine. It lowers LDL and raises HDL. It can cause muscle and belly pain.
PCSK-9 Inhibitors reduce the effects of the liver enzyme that makes cholesterol. They can cause a stuffy nose, chills and fever, swelling at the injection site, and muscle soreness.
Fibrates bind to cholesterol in your intestines to reduce absorption into the bloodstream.

Your Body Needs Some Cholesterol
Some cholesterol is necessary for everyone. Your body makes vitamin D from cholesterol, and vitamin D helps your body absorb calcium to help protect your bones. Your body also makes several hormones from cholesterol and cholesterol also helps you digest some food components. More than 25 percent of your cholesterol is in your brain, and very low blood levels of cholesterol may harm your brain.

More than 80 percent of the cholesterol in your body is made by your liver, and the rest comes from the food you eat. Dietary cholesterol is found only in animal foods, such as eggs, meat, and poultry. It is not found in plants. If you are a vegan and get no cholesterol at all from your food, your own liver will make as much as you need.

My Recommendations
Having blood levels of the bad LDL cholesterol greater than 100 mg/dL puts you at increased risk for suffering a heart attack. Lowering the bad LDL cholesterol with diet, exercise and weight control is both safe and effective in helping to prevent heart attacks.

Many studies have shown that lowering high levels of the bad LDL cholesterol with drugs is effective in preventing heart attacks, and most doctors recommend medications to reduce high levels of LDL cholesterol to below 70 mg/dL. Increasing evidence suggests that lowering LDL with drugs even more helps prevent heart attacks even more.

If you are healthy, I believe that you should aim to keep your LDL cholesterol under 100 mg/dL. If you have major risk factors for a heart attack or have had a heart attack, you should aim to get your LDL cholesterol below 70 mg/dL. There is evidence that getting your LDL as low as possible helps to prevent heart attacks even more, but such low levels may have increased side effects.