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Low Cholesterol May Raise Your Alzheimer’s Risk

cholesterol-hypothesis-wrong-malcolm-kendrick

cholesterol-hypothesis-wrong-malcolm-kendrick [1]

Low Cholesterol May Raise Your Alzheimer’s Risk

by Dr. Mercola [2]
Mercola.com [2]

While cholesterol [3] 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 [4], 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 [5] 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.

According to the authors, “A dietary pattern with relatively high caloric intake from carbohydrates and low caloric intake from fat and proteins may increase the risk of mild cognitive impairment or dementia in elderly persons.” A ketogenic diet benefits your brain in a number of different ways. For example, it:

Triggers ketone production — A cyclical ketogenic diet will help you convert from carb-burning mode to fat-burning mode, which in turn triggers your body to produce ketones, an important source of energy (fuel) for your brain16 that have been shown to help prevent brain atrophy and alleviate symptoms of Alzheimer’s.17 They may even restore and renew neuron and nerve function in your brain after damage has set in.

Improves your insulin sensitivity — A cyclical ketogenic diet will also improve your insulin sensitivity, which is an important factor in Alzheimer’s.18 The link between insulin sensitivity and Alzheimer’s is so strong, the disease is sometimes referred to as Type 3 diabetes.

Even mild elevation of blood sugar is associated with an elevated risk for dementia.19 Diabetes and heart disease20 are also known to elevate your risk, and both are rooted in insulin resistance.

The connection between high-sugar diets and Alzheimer’s was also highlighted in a longitudinal study published in the journal Diabetologia in January 2018.21 Nearly 5,190 individuals were followed over a decade, and the results showed that the higher an individual’s blood sugar, the faster their rate of cognitive decline.

Studies have also confirmed that the greater an individual’s insulin resistance, the less sugar they have in key parts of their brain, and these areas typically correspond to the areas affected by Alzheimer’s.22,23

Reduces free radical damage and lowers inflammation in your brain — Ketones not only burn very efficiently and are a superior fuel for your brain, but also generate fewer reactive oxygen species and less free radical damage.

A ketone called beta hydroxybutyrate is also a major epigenetic player, stimulating radical decreases in oxidative stress by decreasing NF-kB, thus reducing inflammation and increase NADPH [6] levels along with beneficial changes in DNA expression that improve your detoxification and antioxidant production.

I explain the ins and outs of implementing this kind of diet, and its many health benefits, in my new book “KetoFast [7].” In it, I also explain why cycling through stages of feast and famine, opposed to continuously remaining in nutritional ketosis, is so important.

Phospholipid-Bound DHA Is Particularly Important for Those Genetically Predisposed for Alzheimer’s

A type of fat that is of particular importance for your brain health and prevention of neurodegeneration is the marine-based omega-3 fat [8] docosahexaenoic acid (DHA), found in fatty fish, fish oil and krill oil.

Research24 by a biomedical research scientist on aging, Rhonda Patrick, Ph.D., highlights the benefits of DHA bound to phospholipids — such as that found in krill oil — showing this particular form may actually reduce the risk of Alzheimer’s [9] in those with the APOE4 gene, which is thought to be present in about one-quarter of the population.

Having a single copy of the gene raises your risk two- to threefold. For those with two copies, the risk of Alzheimer’s is as much as 15 times higher than those without this genetic predisposition.

Two hallmarks of Alzheimer’s are amyloid beta plaques and tau tangles, both of which impair normal brain functioning. Alzheimer’s patients also have reduced glucose transport into their brains, and this is one of the reasons why plaque and tangles form and accumulate. As explained by Patrick in her press release:25

“DHA promotes brain glucose uptake by regulating the structure and function of special proteins called glucose transporters located at the blood-brain barrier, the tightly bound layer of cells that limits passage of substances into the brain …

DHA … naturally occurs in a triglyceride form and a phospholipid form. Eating DHA-rich fish slows the progression of Alzheimer’s disease and improves symptoms in APOE4 carriers. However, some evidence suggests that taking DHA supplements, which largely lack the phospholipid form, does not.”

According to Patrick, this variation in response appears to be related to the different ways in which the two forms of DHA are metabolized and ultimately transported into your brain.

DHA in Phospholipid Form May Be Ideal for High-Risk Individuals

When the triglyceride form of DHA is metabolized, most of it turns into non-esterified DHA, while the phospholipid form is metabolized primarily into DHA-lysophosphatidylcholine (DHA-lysoPC). While both of these forms can cross the blood-brain barrier to reach your brain, the phospholipid form does so far more efficiently. Patrick explains:26

“Whereas non-esterified DHA passes through the blood-brain barrier via passive diffusion, the phospholipid form, DHA-lysoPC, enters via a special transporter called Mfsd2a.

Previous studies have found APOE4 disrupts the tight junctions of the blood-brain barrier, leading to a breakdown in the barrier’s outer membrane leaflet and a subsequent loss of barrier integrity. One end result of this loss is impaired diffusion of non-esterified DHA.”

According to Patrick, people with APOE4 have a faulty non-esterified DHA transport system, and this may be why they’re at increased risk for Alzheimer’s. The good news is that DHA-lysoPC can bypass the tight junctions, thereby improving DHA transport, and for those with one or two APOE4 variants, taking the phospholipid form of DHA may therefore lower their risk of Alzheimer’s more effectively.

“When looking at the effects of DHA on cognitive function in people with APOE4-related Alzheimer’s disease, it’s important that researchers consider the effects of DHA in phospholipid form, especially from rich sources such as fish roe or krill, which can have as much as one-third to three-quarters of the DHA present in phospholipids,” Patrick says.27

“That’s where we’re most likely to see the greatest benefits, particularly in vulnerable APOE4 carriers.”

Alzheimer’s Prevention Basics

One of the most comprehensive assessments of Alzheimer’s risk is Dr. Dale Bredesen’s ReCODE protocol, which evaluates 150 factors known to contribute to the disease. This protocol also identifies your disease subtype or combination of subtypes so that an effective treatment protocol can be devised.

You can learn more about this in “ReCODE: The Reversal of Cognitive Decline [10],” which includes my interview with him.

In his book, “The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline,”28 which describes the complete protocol, you will also find a list of suggested screening tests and the recommended ranges for each test, along with some of Bredesen’s treatment suggestions.

If you’re concerned about Alzheimer’s, I highly recommend picking up a copy of Bredesen’s book. You can also find some of the program details in his 2014 case paper, which you can download for free online.29 Following are some of the lifestyle strategies Bredesen describes that I believe to be among the most important:

Read the full article at Mercola.com [2]

References

1 Great Plains Laboratory November 16, 2015 [27]

2 Drperlmutter.com, Your Brain Needs Cholesterol [28]

3, 14 MIT.edu APOE-4: The Clue to Why Low Fat Diet and Statins May Cause Alzheimer’s by Stephanie Seneff [29]

4, 5 ZoeHarcombe.com, We have got cholesterol completely wrong [30]

6, 7 JAMA Neurology 2014;71(2):195-200 [31]

8 Medical News Today December 31, 2014 [32]

9 American Journal of Geriatric Psychiatry 2008 Sep;16(9):781-5 [33]

10 Alzheimer’s and Dementia July 2018; 14(7): 952-960 [34]

11 The Conversation March 5, 2018 [35]

12 Neurobiology of Disease July 2019; 127: 449-461 [36]

13 Science Daily April 23, 2019 [37]

15 J Alzheimers Dis. 2012; 32(2):329-339 [38]

16 British Journal of Nutrition 2015 Jul 14;114(1):1-14 [39]

17 Blogs.PLOS.org, July 16, 2016 [40]

18 JAMA Neurology July 27, 2015. doi:10.1001/jamaneurol.2015.0613v [41]

19 NEJM August 8, 2013; 369:540-548 [42]

20 Medicinenet.com March 31, 2014 [43]

21 Diabetologia (2018) DOI: 10.1007/s00125-017-4541-7 [44]

22 JAMA Neurology 2015;72(9):1013-1020 [45]

23 Huffington Post July 29, 2015 [46]

24 FASEB Journal October 5, 2018 [47]

25, 26, 27 PR Newswire October 25, 2018 [48]

28 Amazon.com, The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline, by Dr. Dale Bredesen [49]

29 Aging September 27, 2014; 6(9): 707-717 [50]

30 Journal of Neuroscience, April 27, 2005: 25(17); 4217-4221 [51]

31 The American Journal of Geriatric Psychiatry March 2018; 26(3): 266-277 [52]

32 Deccan Chronicle January 24, 2018 [53]

33 Brain Research 2006; 1122(1):56-64 [54]

34 European Journal of Nutrition 2011; 50(3):151-161 [55]

35 BioRxiv May 19, 2016 [56]

36 Journal of Cellular and Molecular Medicine 2013; 17(8):958 [57]

37 The Root Cause in the Dramatic Rise of Chronic Disease, May 2016 [58]

38 Journal of Neuroscience 19 March 2014, 34(12): 4418-4431 [59]

39 Penn Medicine Press Release March 18, 2014 [60]

40 Medical News Today March 20, 2014 [61]

41 Neurobiology of August 2014; 35(8): 1813-1820 [62]

The Great Cholesterol Con
The Truth About What Really Causes Heart Disease and How to Avoid It
by Dr. Malcolm Kendrick

the-great-cholesterol-con [63]

FREE Shipping available! Order here [63].

Synopsis

Statins are widely prescribed to lower the blood cholesterol levels and claim to offer unparalleled protection against heart disease.

Believed to be completely safe and capable of preventing a whole series of other conditions, they are the most profitable drug in the history of medicine.

In this groundbreaking book, GP Malcolm Kendrick exposes the truth behind the hype. He will change the way we think about cholesterol forever.

About the Author

Dr. Kendrick is a GP in Macclesfield UK. He writes for Pulse magazine in the UK, and redflagsweekly, an online health magazine based in Canada. He has written technical papers on insulin resistance and multiple sclerosis.

Order Here. [63]