Acetylcholine
Episodes
Micronutrient deficiencies, even mild ones, can quietly erode health over decades, raising the risk of chronic disease. One framework...
Choline is an essential nutrient that plays important roles in human health. It provides methyl groups for many aspects of metabolism, is a component of cell...
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Micronutrient deficiencies, even mild ones, can quietly erode health over decades, raising the risk of chronic disease. One framework...
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Choline is an essential nutrient that plays important roles in human health. It provides methyl groups for many aspects of metabolism, is a component of cell...
Topic Pages
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Choline
Acetylcholine is synthesized from choline by choline acetyltransferase and hydrolyzed back to choline by acetylcholinesterase.
News & Publications
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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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Botox injections may impair a person's interpretation of facial expressions. www.newscientist.com
Botox injections in the forehead may impair a person’s interpretation of facial expressions, according to a new study. Brain scans showed that when people who had Botox injections viewed emotional facial expressions, they exhibited altered activity in their amygdala – an area of the brain involved in processing fearful and threatening stimuli.
Researchers injected Botox into the glabellar muscles (responsible for frowning) of 10 women. Using functional magnetic resonance imaging, they measured the women’s brain activity while viewing emotional faces, both before and after the injections.
They found that activity in the amygdala was altered when viewing both happy and angry faces. Similarly, activity in the fusiform gyrus (an area of the brain involved in the processing of faces) was altered when viewing happy faces.
Botox is the tradename for botulinum toxin A, a prescription medication derived from a neurotoxin produced by the bacterium Clostridium botulinum. It is commonly used to temporarily reduce the appearance of skin wrinkles and works by inhibiting the release of acetylcholine (a neurotransmitter) at motor nerve endings.
The findings from this small study suggest that Botox injections in the forehead impair the interpretation of emotional expressions. They also support what is referred to as the facial feedback hypothesis, which asserts that when we see an emotional expression on a face, we respond by trying to recreate the expression. Doing so helps us identify and experience the emotions we see. Larger studies are needed to confirm these findings.
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Prenatal choline supplementation may reduce mental illness risk in children born to Black mothers. www.eurekalert.org
Choline, a phospholipid compound present in a wide range of foods, is an essential nutrient that plays critical roles in building cell membranes and producing the neurotransmitter acetylcholine. Previous research indicates that supplemental prenatal choline improves cognitive ability, attention, and social behavior in children up to seven years of age. A pair of papers published this year explores the effects of prenatal choline supplementation on pregnancy outcomes and neuropsychiatric disease risk in Black Americans.
Neuropsychiatric diseases – commonly referred to as mental illnesses – impair the ability of affected persons to learn and work, imposing an immense burden on society. Physiological alterations that drive neuropsychiatric diseases impair normal brain function, emotion, and mood, and can arise from both genetic factors and environmental factors present before and after birth. One of the physiological alterations commonly observed with neuropsychiatric diseases is impaired suppression of irrelevant environmental mental stimuli, contributing to low mood, poor cognitive functioning, and sensory sensitivities.
Maternal stressors during pregnancy, including nutritional deficiencies, are associated with an increased risk of neuropsychiatric diseases such as schizophrenia, attention deficit disorder, and autism. Epidemiological research has revealed systemic health disparities that contribute to poorer health outcomes for Black Americans, including higher rates of neuropsychiatric diseases. Nutritional interventions may be effective in preventing and treating neuropsychiatric diseases by promoting healthy brain physiology.
The investigators collected data from two observational studies and a randomized clinical trial. In the first observational study, the investigators collected data from 183 pregnant females of varying ethnic identities from the United States at 14 to 16 weeks' gestation. In a second observational study, the investigators collected data from 166 pregnant females from rural Uganda at 18 to 25 weeks' gestation. Finally, in a randomized trial of choline supplementation, 100 pregnant females consumed 3,600 milligrams of choline each morning and 2,700 milligrams each night from week 16 of gestation until delivery. For each study, the investigators measured plasma concentrations of choline and the stress hormone cortisol; maternal mood and stressors; newborn P50 recording; and infant and childhood behavior measures.
Black American females had lower plasma choline concentrations at 16 weeks’ gestation compared to white American females and rural Ugandan females. These lower choline levels were associated with higher maternal concentrations of cortisol and with shorter gestation and decreased P50 inhibition, which both indicate immature neural development at birth. At three months of age, infants born to Black American mothers who had lower gestational choline presented with decreased attention and relation to caregivers, a risk factor for mental illness.
These findings suggest that the cognitive and behavioral deficits associated with lower prenatal choline may predispose children born to Black American mothers to later neuropsychiatric diseases. Prenatal choline or phosphatidylcholine supplementation may reduce disease risk.
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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