Despite growing awareness that cholesterol—whether in the diet or in the human body—isn’t a one-way ticket to certain disease and death, some doctors are still quick to reach for the prescription pad when total cholesterol is over 200 mg/dL, even though statins come with a fairly horrifying list of potential adverse effects. Rather than existing solely to “clog the arteries,” cholesterol is increasingly being shown to be protective for various aspects of physical and mental health.
Just like urea, just like reactive oxygen species, substances we produce naturally can get into trouble when regulatory mechanisms break down, but it’s unlikely the human body would produce so much cholesterol if its multiple fates were all harmful. To the contrary, it looks more and more like cholesterol has beneficial effects we’re only beginning to uncover.
Cholesterol Beneficial for Multiple Sclerosis
A study in Nature found dietary cholesterol to be highly beneficial in a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE). The authors wrote, “Supplemented cholesterol can directly support myelination by incorporation into myelin membranes. […] The current study suggests that cholesterol provides a ‘fast track’ to remyelination and repair.” Not bad for something we were cautioned to avoid at all costs. (Who could forget the 1984 TIME magazine cover with the frowny face made out of bacon and eggs?)
The same authors had shown in previous animal models that “cholesterol is rate limiting for CNS myelination.” Obviously, the body produces cholesterol on its own, but in some individuals, endogenous synthesis may be inadequate to keep up with demand. For these people, cholesterol may be considered “conditionally essential,” and they might rely on a steady supply of cholesterol from their diet.
According to the study, “Dietary cholesterol modulates the profile of growth factors, simultaneously enhancing OPC [oligodendrocyte precursor cell] proliferation and oligodendrocyte differentiation, thereby facilitating remyelination and reducing axonal injury.” Increased dietary cholesterol, delivered via a chow of 2% or 5% cholesterol, “directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning.”
The authors note that patients with MS have disturbed brain lipid metabolism, but serum lipids are in the normal range. During active disease and disease progression, however, total cholesterol levels often rise to the upper limit of the normal range. It’s not known whether this is a cause or consequence—being that cholesterol is so critical for remyelination, ramping up cholesterol synthesis may be the body’s way of trying to provide more of this essential substance. For those whose endogenous synthesis is inadequate, increasing dietary cholesterol may be helpful: “arrested repair can be overcome by increasing the local availability of cholesterol which we achieved by nutritional supplementation.”
Pooling these findings on the animal model of MS with previous findings regarding other demyelinating disorders, the researchers wrote:
“Taken together, our data show that demyelinating disease destabilizes peripheral and CNS cholesterol homoeostasis. Dietary cholesterol supplementation supports cholesterol metabolism in the CNS and has the remarkable potential to ameliorate disease by facilitating several repair mechanisms, leading to improved remyelination and neurological outcome. This study highlights the safety of dietary cholesterol and might have implications for the management of demyelinating diseases…”
Beyond MS: Cholesterol Helpful for ALS and Mental Health
Multiple sclerosis isn’t the only condition where increased cholesterol could be of benefit. It’s been observed that higher cholesterol—including LDL—is associated with increased lifespan in amyotrophic lateral sclerosis (ALS). The title of one study says it all: Dyslipidemia is a protective factor in amyotrophic lateral sclerosis. Perhaps it’s time to stop calling it dyslipidemia, as the “dys” implies something dysregulated, abnormal, or harmful. In the case of ALS, and possibly other neurodegenerative disorders, elevated cholesterol may be desirable. (Higher cholesterol is associated with reduced risk for dementia, as well as lower all-cause mortality, especially in older people.)
In ALS patients, “an abnormally elevated LDL/HDL ratio significantly increased survival by more than 12 months.” Maybe it’s not really abnormal, then, but actually the body trying to protect and sustain itself. It only seems “abnormal” when we operate under the premise that LDL is unquestionably harmful and should always be kept low—a premise increasingly shown to be incorrect.
The ultimate cause of death for most patients with ALS is respiratory failure, which progresses slowly over months, as nerve damage impairs function of the diaphragm. Some evidence indicates that respiratory impairment is associated with a decrease in blood lipids and a lower LDL/HDL ratio. In one study of 658 ALS patients, those with forced vital capacity (FVC) <70% had lower total cholesterol, HDL, triglycerides, and LDL/HDL ratios compared to those with FVC ≥90%. (In the interest of full disclosure, this study did not find a correlation between higher LDL and increased survival.)
Other research on ALS supports the beneficial role of cholesterol:
“In experimental models of peripheral nerve injury, there is a dramatic increase in the expression of low-density lipoprotein receptors which allow the regenerating nerve to import cholesterol into the cell, possibly bound to Apolipoprotein E, for the purpose of axonal repair. Exogenous low-density lipoproteins, but not high-density lipoproteins, can rescue axonal growth after it has been suppressed by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statin drugs) in cultured sympathetic neurons. Thus, elevated dietary fats may result in elevated circulating low-density lipoprotein levels which, in turn, could lead to improved survival of peripheral motor neurons.”
Low cholesterol is also associated with violent behavior and substantially increased risk for suicide. In a cohort of Canadian subjects, individuals in the lowest quartile of serum total cholesterol (<4.27 mmol/liter or ~165 mg/dl) had more than six times the risk of committing suicide compared to subjects in the highest quartile (>5.77 mmol/liter or ~223 mg/dl).
It’s long past time to rethink cholesterol. It may not be desirable to have total cholesterol or LDL through the roof, but increasing evidence suggests low cholesterol may be far more problematic than high cholesterol across a number of health concerns.