Low Cholesterol May Raise Your Alzheimer’s Risk by Dr. Joseph Mercola for Mecola
While cholesterol has been vilified as something that should be as low as possible to prevent heart disease, it’s actually a crucial component for good health and too low a level can have serious repercussions for your health.
Cholesterol is found not only in your bloodstream but also in every cell in your body, and is necessary for the production of cell membranes, virtually every steroid hormone, vitamin D and bile acids that help you digest fat.
Cholesterol also plays an important role in the formation of memories and is vital for healthy neurological function. For example, low cholesterol levels have been shown to increase your risk of depression and suicide,1 in some cases rather dramatically.
As noted by neurologist Dr. David Perlmutter, a quarter of all the cholesterol in your body is found in your brain, where it performs the function of an antioxidant.2 A number of studies have demonstrated that, contrary to popular belief, higher cholesterol levels are associated with better brain health.
According to senior research scientist Stephanie Seneff, Ph.D., insufficient fat and cholesterol in your brain play a crucial role in the Alzheimer’s disease process, detailed in her 2009 paper3 “APOE-4: The Clue to Why Low Fat Diet and Statins May Cause Alzheimer’s.”
As noted by nutritional researcher Zoe Harcombe, a researcher in dietary fat who has a Ph.D. in public health nutrition, “It is virtually impossible to explain how vital cholesterol is to the human body. If you had no cholesterol in your body you would be dead.”4
Your liver manufactures most, about 80 percent, of the cholesterol your body requires, which in and of itself suggests your body cannot survive without it. The remaining 20% comes from your diet. However, dietary cholesterol is absorbed at a rate of 20% to 60% depending on the individual, and if you consume less, your body will compensate by making more and vice versa.
In order to be transported through your bloodstream, the cholesterol is encapsulated in a lipoprotein, which is where the terms LDL (low-density lipoprotein), HDL (high-density lipoprotein) and VLDL (very-low-density lipoprotein) come from. Whether LDL is truly as hazardous as many in the medical community insist, however, is still up for debate.
According to Harcombe, the notion that there is good (referring to HDL) and bad (LDL) cholesterol is incorrect, as technically LDL and HDL are not even cholesterol; they’re carriers and transporters of cholesterol, triglycerides (fat), phospholipids and proteins. “LDL would more accurately be called the carrier of fresh cholesterol and HDL would more accurately be called the carrier of recycled cholesterol,” Harcombe explains.5
Now, HDL is indeed beneficial in that it acts as a master manager, helping protect LDL against oxidation and transporting triglycerides and cholesterol in and out of the VLDL. In a healthy person, the LDL will be reabsorbed by the liver after about two days, where it gets broken up and recycled. As a general rule, a high-sugar diet will cause damaged LDLs to rise, beneficial HDLs to drop, triglycerides and, often, total cholesterol to rise.
How Cholesterol Impacts Neurological Function and Disease Risk
Getting back to Alzheimer’s, a number of studies have demonstrated the importance of higher cholesterol for the prevention of this devastating neurodegenerative disease. In 2014, a study6 in JAMA Neurology investigated the impact of cholesterol levels on the deposition of beta-amyloid plaque in the brains of 74 seniors with a mean age of 78. Three of them had mild dementia, 33 were clinically normal and 38 had mild cognitive impairment. As explained by the authors:7
“Cholesterol, vital to neuronal structure and function, has important roles in the synthesis, deposition, and clearance of β-amyloid (Aβ) and may have a pathogenic role in Alzheimer disease (AD) … There are also important connections among apolipoprotein E (APOE), Aβ, and cholesterol.
A strong genetic risk factor for AD, the APOE ε4 allele is associated with earlier and higher deposition of Aβ. APOE is the primary transporter of cholesterol in the brain, and its isoforms differentially modulate brain cholesterol levels.”
Here, the researchers found that higher levels of HDL and lower levels of LDL were associated with a reduced risk for amyloid plaque deposits in the brain, and these findings were independent of age and presence of the APOE4 gene. Study co-author Dr. Charles DeCarli, a professor of neurology at UC Davis and director of the UC Davis Alzheimer’s Disease Center, commented on the results:8
“If you have an LDL above 100 or an HDL that is less than 40 … you want to make sure that you’re getting those numbers into alignment. You have to get the HDL up and the LDL down.”
That said, research9 published in 2008 found that elderly individuals who were not genetically predisposed to Alzheimer’s disease who had the highest levels of cholesterol — including the highest levels of LDL — had the best memory, so the verdict is still out on whether high LDL is a significant risk factor.
Another study 10, 11 published in 2018 similarly came to a similar, although more complex, conclusion. In this study, the researchers evaluated the total cholesterol levels of participants in the Framingham Heart Study at midlife (around the age of 40) and late-life (around the age of 75). They also assessed mean total cholesterol between midlife and late life, and the total change in cholesterol since midlife.
Here, they found that having higher total cholesterol at midlife was associated with a reduced risk for cognitive decline after the age of 85. However, those whose cholesterol levels increased between midlife and late life were at increased risk, suggesting there are likely other unknown variables at play as well.
New Theory Proposed
In related news, researchers at Florida Atlantic University’s (FAU) Brain Institute and Vanderbilt University have proposed a new theory to help explain the link between cholesterol, beta-amyloid and Alzheimer’s. The study,12 published in Neurobiology of Disease in July 2019, tracked the location and mobility of amyloid precursor protein to assess its function in neurons.
Amyloid precursor protein is strongly associated with Alzheimer’s, but its distribution across various brain membranes and neuronal functions are still unclear. As reported by Science Daily:13
“In the case of more common sporadic Alzheimer’s disease, the highest genetic risk factor is a protein that is involved in cholesterol transportation and not this amyloid precursor protein … For the study, [Qi] Zhang [Ph.D., senior author and researcher at FAU Brain Institute] and collaborators genetically disrupted the interaction between cholesterol and amyloid precursor protein.
Surprisingly, by disengaging the two, they discovered that this manipulation not only disrupts the trafficking of amyloid precursor protein but also messes up cholesterol distribution at the neuronal surface.
Neurons with an altered distribution of cholesterol exhibited swollen synapses and fragmented axons and other early signs of neurodegeneration. ‘Our study is intriguing because we noticed a peculiar association between amyloid precursor protein and cholesterol that resides in the cell membrane of synapses, which are points of contact among neurons and the biological basis for learning and memory,’ said Zhang.
‘Amyloid precursor protein may just be one of the many accomplices partially contributing to cholesterol deficiency. Strangely, the heart and brain seem to meet again in the fight against bad cholesterol.'”
High-Fat Ketogenic Diet Protects Your Brain Health
As noted by Seneff in her 2009 paper14 on Alzheimer’s:
“ApoE-4 … is a known risk factor [for Alzheimer’s disease]. Since apoE plays a critical role in the transport of cholesterol and fats to the brain, it can be hypothesized that insufficient fat and cholesterol in the brain play crucial role in the disease process.
In a remarkable … study, it was found that Alzheimer’s patients have only 1/6 of the concentration of free fatty acids in the cerebrospinal fluid compared to individuals without Alzheimer’s. In parallel, it is becoming very clear that cholesterol is pervasive in the brain, and that it plays a critical role both in nerve transport in the synapse and in maintaining the health of the myelin sheath coating nerve fibers …
Throughout a person’s life, the myelin sheath has to be constantly maintained and repaired. This is something that researchers are only beginning to appreciate, but two related properties of Alzheimer’s are poor quality myelin sheath alongside a drastically reduced concentration of fatty acids and cholesterol in the cerebrospinal fluid …
An extremely high-fat (ketogenic) diet has been found to improve cognitive ability in Alzheimer’s patients. These and other observations … lead me to conclude that both a low-fat diet and statin drug treatment increase susceptibility to Alzheimer’s.”
Indeed, I’ve previously written about how a ketogenic diet, high in healthy fats, helps protect against neurodegenerative diseases such as Alzheimer’s. One of the most striking studies15showing the effects of a high-fat/low-carb versus high-carb diets on brain health revealed that high-carb diets increase your risk of dementia by a whopping 89 percent, while high-fat diets lower it by 44 percent.