Can Cholesterol Be Too Low?

Cholesterol is in the membrane of every cell in your body and is essential to making certain vitamins and hormones, produces bile acids so that you can digest and absorb nutrients, and plays a role in the release of neurotransmitters in the brain, so it would make logical sense that too low of levels might be adverse to good health. This query is indeed not novel; way back in 1994, the American Heart Association Task Force on Cholesterol Issues noted an increase in deaths from trauma, cancer, hemorrhagic stroke, respiratory diseases, and infectious disease among people with total cholesterol levels below 160 mg/dl. However, they also noted that a substantial portion of these diseases seemed due to poor health unrelated to cholesterol levels. So…not very helpful.

The question matters because too much cholesterol creates sticky plaques along the walls of the arteries. These plaques, over time, can impede or prevent the flow of blood to the brain, heart, and other important organs, and cause your risk of suffering a heart attack or stroke to skyrocket. You obviously don’t want your levels to be high, but it would be helpful to know if there’s a level at which the lowering of blood lipids ceases to be advantageous and becomes dangerous.

Sometimes unusually low cholesterol occurs in tandem with some very undesirable health conditions, like cancer. Very low cholesterol has also been associated with hemorrhagic stroke, depression, anxiety, and, in pregnant women, preterm birth and low birth weight. This is a classic “chicken or the egg” situation. Was the person’s cholesterol low because they were depressed, or did their depression cause the cholesterol level to plummet?

There is no formal definition of very low LDL cholesterol, but it’s probably <40 mg/dl. Many experts believe that chronically low levels impair the activity of the brain and hormones. They hypothesize that the depletion of LDL increases oxidative stress in the brain, which negatively affects both brain function and vascular integrity.  Observational studies have shown a link between low LDL and increased mortality in the general population, especially in the elderly and patients who have suffered a heart attack or who have community-acquired pneumonia. In patients with sepsis, low cholesterol has been suggested as a marker for poor prognosis.

Hypobetalipoproteinemia, an inherited disorder that results in severely low levels of LDL, can cause fat malabsorption and hepatic steatosis that sometimes progresses to cirrhosis and hepatocellular carcinoma. Many sufferers experience malnutrition and wasting. Individuals with the condition have been determined to have an increased chance of suffering a hemorrhagic stroke and are more likely to be diagnosed with depression.  They also often experience eye problems related both to deficiencies of fat-soluble vitamins A and D and to the fact that the lens of they eye synthesizes cholesterol for structure and clarity. Their LDL levels are typically below the 5th percentile.

Low LDL levels have also been associated with the dysregulation of Tumor Necrotizing Factor Alpha, which is related to cancer, major depression, and Alzheimer’s disease. Monkeys on a low-fat or low-cholesterol diet have decreased serotonin levels in their brains.  Researchers at the Duke University Medical Center determined that healthy, young women with a total cholesterol level of less than 160 mg/dl were more likely to experience depression or anxiety, compared to those with normal or high levels. Low cholesterol levels have even been linked to suicide, as well as impulsive and aggressive behavior. Again, it’s possible that depressed or violent individuals tend to eat very little and therefore have low blood lipids. Interestingly, large trials of statins have found no increased risk of suicide or any differences in performance on neuropsychological tests, memory, or executive function, even when LDL was as low as 25 mg/dl.

A recent meta-analysis determined that extremely low LDL levels had no impact on steroid hormone and bile acid production or the central nervous system (which is protected by a cholesterol blood-brain barrier according to the authors). They hypothesize that “any correlation to disease is explained as a secondary phenomena” and state that in individuals with an LDL that is already below 70 mg/dl, decreasing it another 38.7 mg/dl drops the risk of major cardiovascular event another 20%. Still, treating cholesterol of 200 mg/dl to a target of 100 mg/dl will almost certainly achieve a more significant clinical benefit that treating cholesterol of 100 mg/dl to a goal of 50 mg/dl will. It is questionable whether taking already-low cholesterol even lower warrants the addition of another drug. It’s vitally important to note that there have only been two years of follow-up so far, and scientists are far from reasonably stating that there is no level of LDL that is too low.