Acetylcholine
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Choline
Acetylcholine is synthesized from choline by choline acetyltransferase and hydrolyzed back to choline by acetylcholinesterase.
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A moderate intake of choline—two to three eggs worth—may cut your risk of cognitive decline in half. www.ncbi.nlm.nih.gov
Cognitive decline is a growing concern as populations age, and diet may play a key role in preserving cognitive function. A 2021 study found that people with moderate choline intake—about the amount in two to three eggs or a serving of salmon—were half as likely to experience cognitive decline than those with low intake.
Researchers categorized roughly 2,400 older adults enrolled in NHANES based on their daily choline intake: low (less than 188 milligrams), moderate (188 to 400 milligrams), or high (more than 400 milligrams). Then, they ranked them according to their performance on various cognitive tests.
They found that people with moderate choline intake were 33% to 50% less likely to have low cognitive function than those with the lowest intake. Interestingly, those with higher intake didn’t perform better on the cognitive tests, suggesting a “sweet spot” for choline intake.
These findings indicate that incorporating moderate amounts of choline-rich foods into one’s diet may protect brain health during aging. This protective effect may be due to choline’s role in producing acetylcholine, a neurotransmitter involved in neurogenesis, synapse formation, learning, and memory. In addition, research in animal models shows that choline deficiency increases the risk of Alzheimer’s disease and damages vital organs in mice.
Choline is found in many foods. Good sources of this essential nutrient include: - Eggs (1 large): ~147 milligrams - Fish (salmon, 3 ounces, cooked): ~187 milligrams - Cauliflower (1 cup, cooked): ~72 milligrams - Beef (3 ounces, cooked): ~78 milligrams Learn more about choline’s role in brain health in this Q&A featuring Dr. Rhonda Patrick.
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Lifelong choline supplementation provides a potential shield against Alzheimer's disease in mice. www.ncbi.nlm.nih.gov
Choline, an essential nutrient found in eggs, meat, fish, beans, and nuts, supports the production of acetylcholine, a neurotransmitter involved in neurogenesis, synapse formation, learning, and memory. Most people living in the US don’t consume enough choline – 550 milligrams per day for men and 425 milligrams per day for women – potentially increasing their risk for various diseases. A 2019 study in mice found that lifelong choline supplementation prevented Alzheimer’s disease and preserved cognitive function.
Researchers fed mice susceptible to developing Alzheimer’s disease a regular diet or a diet supplemented with choline from early life to old age. When the mice reached the age of 10 months, the researchers assessed the animals' memory function and examined their brain tissue.
They found that mice that received lifelong choline supplementation had better spatial memory and fewer amyloid-beta plaques in their brains than those on a regular diet. They also found that the mechanisms driving these effects were related to reduced amyloid-beta peptide synthesis, a dampened microglia inflammatory response, and downregulation of the alpha-7 nicotinic acetylcholine and sigma-1 receptors, both of which are critical for various neurological processes.
These findings suggest that lifelong choline supplementation mitigates Alzheimer’s disease pathology and maintains cognitive function in mice susceptible to the disease. Other research showed that mice that ate a choline-poor diet had higher brain levels of amyloid-beta and tau – two proteins implicated in the pathogenesis of Alzheimer’s disease – than those that ate a choline-rich diet. The mice that ate a choline-poor diet also gained weight, showed signs of altered metabolism, liver damage, and enlarged hearts, and performed poorly on motor skills tests.
More than 55 million people worldwide live with Alzheimer’s disease. Learn more about the disease and how to prevent it in this episode featuring Dr. Dale Bredesen.
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Female sex hormone influences Alzheimer's pathology in mice, with implications for prevention and treatment. www.sciencedaily.com
Alzheimer’s disease disproportionally affects women, who account for nearly two-thirds of all cases worldwide. Some evidence suggests female sex hormones influence the pathology and progression of Alzheimer’s disease. A recent study in mice shows that the brains of male and female mice with Alzheimer’s regulate amyloid-beta protein differently, with the hormone estradiol playing a critical role.
Researchers measured amyloid-beta accumulation in male and female mice when exposed to differing levels of cholinergic tone (acetylcholine release). Then, they examined the effects of removing the ovaries (the primary source of estradiol) and estradiol replacement on this relationship. Finally, using magnetic resonance imaging techniques, they assessed the amyloid-beta burden in the brains of 130 older adults.
They found that acetylcholine activity and the development of amyloid-related issues in male and ovariectomized female mice were directly linked. This link, however, was not observed in female mice with intact ovaries or females without ovaries that received estradiol. They also found that the age-related decline in acetylcholine worsens the amyloid-beta burden in older adults.
Amyloid-beta is a toxic protein that clumps together, forming plaques in the brain – a hallmark of Alzheimer’s disease. Cholinergic neurons are vital for cognition and perception. They release acetylcholine, a neurotransmitter that facilitates impulse firing between neurons. Cholinergic neurons are particularly vulnerable to amyloid-beta’s toxic effects, which impair acetylcholine release. The relationship between acetylcholine and amyloid-beta is bidirectional: amyloid-beta aggregation impairs acetylcholine production, in turn increasing amyloid-beta aggregation, creating a vicious cycle.
These findings suggest that estradiol, a female sex hormone, influences amyloid-beta burden in mice. They also highlight the need for Alzheimer’s research to consider sex differences, the relationship between acetylcholine signaling and amyloid-beta buildup, and the effects of sex hormones to better develop treatment strategies.
Heat shock proteins inhibit amyloid-beta clumping and reduce amyloid-beta plaque toxicity. Sauna use increases heat shock protein production and activity, potentially reducing the risk of Alzheimer’s disease. Learn more in our sauna overview article.
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A 28% lower risk of dementia and better cognition was associated with a high intake of dietary phosphatidylcholine mainly from eggs and meat in men. www.sciencedaily.com
A 28% lower risk of dementia and better scores on tests for memory and linguistic abilities was associated with a high intake of dietary phosphatidylcholine mainly from eggs and meat in men.
Choline is an important precursor to the neurotransmitter acetylcholine which plays an important role in cognition. Phosphatidylcholine is a very important component of cell membranes that make up neurons and also combines with the omega-3 fatty acid DHA to form lysophosphatidylcholine DHA which is transported across the blood-brain barrier. I published a paper last year on the important role DHA in phosphatidylcholine form plays in preventing Alzheimer’s disease particularly in people genetically predisposed to the disease.
This new study was an observational study so causation cannot be established. Future clinical trials need to be done before definitive conclusions can be made.
Link to my study on DHA and Alzheimer’s disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338661/
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Supplemental probiotics for 12 weeks improved cognition in Alzheimer's patients & also lowered inflammatory markers. www.sciencedaily.comBrain Alzheimer's Gut Microbiome Inflammation Probiotics Behavior Insulin Triglycerides Dopamine Norepinephrine Acetylcholine
The probiotics also lowered triglycerides, VLDL, and markers of insulin resistance. There was no cognitive improvement in the placebo group.
The participants took 2 billion Bifidobacterium bacteria per day, which is a pretty small quantity of probiotics. It is likely that the probiotics are working through multiple mechanisms such as lowering inflammation and increasing neurotransmitters. Other studies have shown that gut bacteria are able to modulate the levels of GABA, norepinephrine, serotonin, dopamine, and acetylcholine through the gut-brain axis.
I spoke with the gut experts, Drs. Justin and Erica Sonnenburg, about the importance of the gut microbiome in human health and the various foods (ie. fermentable fiber and other prebiotics) that provide our gut bacteria with the food they need to thrive. Here is the interview (also available on iTunes and Sticher): https://www.youtube.com/watch?v=gOZcbNw7sng