Alzheimer's 12: amyloid plaques and tau tangles don't cause Alzheimer's; loss of choline does.
Dr Goodenowe discusses the cause of Alzheimer's. His discussion provokes some research notes on Choline for brain health.
If your time is limited, you can scroll down and read the section entitled-
”Dietary advice for Choline supplementation to prevent and reverse dementia”.
If you apply the advice in this section, you will improve your mental clarity and overall health.
Goodenowe Video 2: restoring choline and acetyl-choline
Picture: In this snapshot from the video, the normal transmitter neurone (pictured at lower right) releases acetylcholine, which travels to the receptor on the receiver neurone and then gets broken down into acetic acid and choline. The choline is then taken back into the transmitter neurone and recycled. When the transmitter neurone membrane is deficient in plasmalogens, the vesicle gets stuck on the membrane and fails to release its acetylcholine contents. The vesicle is then digested via standard cell clean-up mechanisms (this is called autophagy), and the choline is destroyed. This is why plasmalogen deficiency leads to choline deficiency, and the one can worsen the other. See text and video for more detail.
What causes plasmalogen deficiency in the modern western society?
Note: This article and the previous article on Plasmalogens do not discuss what causes Plasmalogen deficiency in modern Western society. Suffice it to say that modern diets are deficient in plasmalogens and the nutrients that would help the body to make them for itself; also our chronic ill health (due to toxic lifestyle and environment) do the rest.
(This is the second video in the series, view the first video here)
Summary of video
Video section A:
Time stamp: 1:00 to 6:20
Dr Goodenowe explains:-
How neurones talk to each other via neurotransmitters (neurotransmitter transmission is turned down when choline and plasmalogens are depleted).
Video section B:
Timestamp: 6:20 to 14:00
Alzheimer’s partial recovery story (Fred and Carolyn Weirs)
Video section C:
Timestamp: 14:20 to 20:10
Dr Goodenowe explains:-
When plasmalogens go down, neurotransmitter firing slows, and neurones shrink back like a tree's roots dying. The neurotransmitter most affected by the loss of Plasmalogens is Acetylcholine.
The functions of memory, movement and high-level cognition, all depend upon the Acetylcholine neurotransmitter. If this neurotransmitter is not released from the neurone, you have the symptoms of Alzheimer's disease.
Video section D:
Timestamp: 20:10 to 27:35
Alzheimer’s partial recovery story (Helen and Ted Goodenowe)
Video section E:
Timestamp: 27:35 – 36:38
Dr Goodenowe explains:-
Amyloid plaques do not disturb neurones or cognitive function. They are associated with Alzheimer’s, but they do not cause Alzheimer’s.
When cell membranes are plasminogen deficient, the Acetylcholine neurotransmitter is not released and gets stuck in the cell membrane. This effectively stops neurones from communicating with each other and also requires a cell clean-up mechanism (autophagy) to destroy the Choline along with the acetylcholine. (In normally functioning brain cells, the Acetylcholine in the synapse is broken down into acetic acid and Choline, and the Choline is recycled into Acetylcholine and other molecules). Since the Choline can no longer be recycled, there is a deficiency of Choline, which, if not replaced in the diet, means that the neurone must scavenge Choline from the Choline containing Plasminogens in its cell membrane. This worsens the Plasminogen deficiency and causes the die-back of the neurone’s branches (similar to the die-back of the roots of a tree).
So when Plasmalogens are low, Choline is low too. And when Choline is low, plasmalogens are low. This can be measured in blood tests.
Homocysteine levels go up when Choline is deficient. Therefore, the blood test for Homocysteine (which you can request from your doctor) provides an approximate measure of how deficient you are in both Choline and Plasmalogens.
Scopalamine, by blocking the acetylcholine neurotransmitter, mimics an Alzheimer's attack, which can be reversed by a drug type called “cholinesterase inhibitor”. Aricept (a Cholinesterase inhibitor) was the first drug (and is still the major drug), for improving Alzheimer’s symptoms. This confirms that impaired Acetylcholine function is a cause of Alzheimer’s disease.
Contrariwise, billions of dollars have been spent trialling drugs that reduce Amyloid plaque, but none of them have worked to reverse or even prevent Alzheimer's. This proves that Plaque does not cause Alzheimer’s (Amyloid is associated with Alzheimer’s, but does not cause Alzheimer’s).
Discussion: choline nutrition can reduce the risk of Alzheimer’s
(A discussion of Plasmalogen nutrition is to be found here).
Amyloid does not cause Alzheimer’s
Dr Goodenowe discusses the cause of Alzheimer's - and backs his finding with hard evidence that Amyloid plaque and Tau tangles may be associated with Alzheimer’s but are not the cause of Alzheimer's. This is why mainstream medical research (which has focused solely on producing an Alzheimer’s “blockbuster” drug that reduces Amyloid) has so far failed to provide a cure or preventative for Alzheimer's. We hope that the pharmaceutical companies will wake up to this soon. In the meantime, there are some very positive Alzheimer's prevention and reversal strategies to be had by following the hypothesis that Alzheimer's is caused by a disruption of the production and supply of the neurotransmitter Acetylcholine.
Acetylcholine: a neurotransmitter that is deficient in Alzheimer’s patients
Early research identified that the acetylcholine neurotransmitter is deficient in Alzheimer's patients. A drug called Aricept (generic name Donepezil – released in March 1997) is still the most widely used Alzheimer’s drug. Despite billions of dollars of (in hindsight) wasted research for a replacement drug - it is still the main drug for Alzheimer's. Note that Aricept does not correct the Acetylcholine deficiency; it merely stimulates faster use of whatever Acetylcholine remains.
Aricept, therefore temporarily improves the speed and accuracy of memory and mental processes but does not reverse the Alzheimer’s decline. To do that, we would need to replace the deficient molecule (Choline) by use of supplements or choline-rich foods, and or treat the disease process that is using up the Choline reserves. That’s the theory. Now for the evidence.
Evidence that Choline supplementation prevents Alzheimer’s
1. A population-wide deficiency of choline
According to a well-referenced article by Dr Mercola, 90% of Americans have a dietary deficiency of Choline. The RDA (recommended daily allowance) for Choline is approximately 500 mgs per day. But this is just a guideline.
2. Choline supplementation evidence
There is good review evidence that Choline improves the memory, mental clarity and motor skills of persons in their retirement years.
However, due to poorly targeted research that assumes that highly processed soy lecithin is equivalent to egg yolk and other less processed lecithin sources, the evidence that choline may prevent Alzheimer’s is currently insufficient. Soy lecithin has potential toxicities that could confound experimental results, whereas egg and other less processed choline sources are likely safer and more likely to have positive effects upon Alzheimers outcomes. For more information on soy lecithin, go to the bottom of this article and look for links to articles by Dr. Kris Kresser and Dr. Axe.
3. Increased requirements in some populations
Endurance athletes, pregnant women, and postmenopausal women all need more.
Those who have a genetic tendency to be poor methylators (MTHFR genetic mutations seriously affect 9% of the population and possibly slightly affect 30% of the population; this is why it is a good idea to do a DNA test and receive genome counselling from a specialist), and these people require more choline by diet and/or supplementation of B vitamins.
Note:
Poor methylators often have a “wired” personality and find it hard to relax and sleep. They also have high levels of homocysteine in their blood tests – high homocysteine is a known risk factor for both heart disease and dementia, and choline supplements normalise blood homocysteine. B vitamins and a diet rich in coloured vegetables and dark leafy greens also help reduce homoscysteine (the Mediterranean diet is one such diet).
Populations that have an increased risk of dementia due to the following illnesses can show improvement in their illness by supplementing with choline
Those with irritable bowel syndrome – due to choline improving the microbiome diversity -are likely to benefit from increased choline in their diet (and thereby reduce their dementia risk).
Those with non-alcoholic fatty liver disease would benefit from Choline supplementation (and thereby reduce their dementia risk).
Those who do not eat an abundance of coloured vegetables and dark leafy greens (which provide the full range of folic acid and not just the standard folic acid found in most commercial supplements) are also likely to need more Choline. (Those who fail to eat an abundance of leafy greens are more likely to suffer dementia).
In my opinion, all of the above high-risk populations would benefit by doubling their choline intake above the official RDI levels to about 1 gram daily. The tolerable upper limit of dietary choline is 3.5 grams. The above populations would likely also benefit from a total intake of leafy greens of up to 6oo grams daily.
Dietary advice for Choline supplementation to prevent and reverse dementia
The simplest dietary recommendation is to eat a Mediterranean diet with plenty of eggs, and avoid processed and packaged foods like the plague that they are!
A little more detail
In today’s toxic environment, you should aim at doubling the recommended dietary intake (the RDI) from 500mg to 1,000mg - especially if you are old, have a chronic disease condition or are pregnant.
Consume two to four eggs daily (provides 240 to 480mg of Choline)
Eat a tin of sardines three times weekly (each tin provides 200mg of choline)*
Eat leafy greens and similar (for example, cauliflower, which has 70 mgs of Choline per 100 grams). Eat 600 grams of leafy greens daily - do this for the mixed B vitamin content which contributes to general health and is choline sparing.
Eat 100 grams of liver, when you can (provides 400 mg of Choline)
Supplement with Krill oil (may have as much as 500 mg of Choline per serving)*
Take choline supplements in capsule form (provides 250 to 500 mg per serve)
*Sardines and krill oil may also provide some of the appropriate plasmalogens. To get the benefit, chew the sardines well so that they can rapidly transit the stomach acid environment (stomach acid destroys plasmalogens).
Happy dementia-free retirement!
References
Association between choline supplementation and Alzheimer’s disease risk: a
Association Between Egg Consumption and Dementia Risk in the EPIC-Spain Dementia Cohort (Eggs are the main source of choline in the Western diet)
Dr Chris Kresser: What Is Choline? Benefits, Sources & Signs of Choline Deficiency
Google search: poor methylators need choline
(“As the major dietary source of methyl groups, choline helps to drive methylation reactions that support cognitive function, fetal neural development and detoxification. Approximately 90% of Americans fall short of meeting adequate dietary intakes”).
Pure Genomics video:-
Methylation Genetics: Why Choline is Often the Missing Link
Choline fact sheet for health professionals (3.5 grams tolerable upper limit)
What's the deal with choline's RDI? Should it be higher? Lower?
“The RDI for men is 550mg, 425mg for women. Actual thresholds for deficiency seem to be all over the place, from 138mg to the 800's - the safe upper limit is 3,500mg daily”.
Alzheimer’s disease: still a perplexing problem
Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men
Choline intake in a large cohort of patients with nonalcoholic fatty liver disease
Is dietary choline intake related to dementia and Alzheimer’s disease risks? Results from the Framingham Heart - Study use link below.
https://ajcn.nutrition.org/article/S0002-9165(23)03647-X/pdf
The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases - use link below.
https://www.frontiersin.org/articles/10.3389/fendo.2023.1085041/full