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Low Cholesterol May Raise Your Alzheimer's Risk

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."

Cholesterol 101

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.

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