An egg a day keeps Alzheimer's away (cuts risk in half)

Association of Egg Intake With Alzheimer’s Dementia Risk in Older Adults: The Rush Memory and Aging Project - July 2024

The Journal of Nutrition, Volume 154, Issue 7 https://doi.org/10.1016/j.tjnut.2024.05.012

Yongyi Pan1 ∙ Taylor C Wallace1,2,3 ∙ Tasija Karosas1 ∙ David A Bennett4 ∙ Puja Agarwal4 ∙ Mei Chung1 mei_chun.chung@tufts.edu

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder with increasing prevalence due to population aging. Eggs provide many nutrients important for brain health, including choline, omega-3 fatty acids, and lutein. Emerging evidence suggests that frequent egg consumption may improve cognitive performance on verbal tests, but whether consumption influences the risk of Alzheimer’s dementia and AD is unknown.

Objectives: To examine the association of egg consumption with Alzheimer’s dementia risk among the Rush Memory and Aging Project cohort.

Methods: Dietary assessment was collected using a modified Harvard semiquantitative food frequency questionnaire. Participants’ first food frequency questionnaire was used as the baseline measure of egg consumption. Multivariable adjusted Cox proportional hazards regression models were used to investigate the associations of baseline egg consumption amount with Alzheimer’s dementia risk, adjusting for potential confounding factors. Subgroup analyses using Cox and logistic regression models were performed to investigate the associations with AD pathology in the brain. Mediation analysis was conducted to examine the mediation effect of dietary choline in the relationship between egg intake and incident Alzheimer’s dementia.

Results: This study included 1024 older adults mean [ ±standard deviation (SD)] age = 81.38 ± 7.20 y}. Over a mean (±SD) follow-up of 6.7 ± 4.8 y, 280 participants (27.3%) were clinically diagnosed with Alzheimer’s dementia. Weekly consumption of >1 egg/wk (hazard ratio [HR]: 0.53; 95% confidence interval [CI]: 0.34, 0.83) and ≥2 eggs/wk (HR: 0.53; 95% CI: 0.35, 0.81) was associated with a decreased risk of Alzheimer’s dementia. Subgroup analysis of brain autopsies from 578 deceased participants showed that intakes of >1 egg/wk (HR: 0.51; 95% CI: 0.35, 0.76) and ≥2 eggs/wk (HR: 0.62; 95% CI: 0.44, 0.90) were associated with a lower risk of AD pathology in the brain. Mediation analysis showed that 39% of the total effect of egg intake on incident Alzheimer’s dementia was mediated through dietary choline.

Conclusions:These findings suggest that frequent egg consumption is associated with a lower risk of Alzheimer’s dementia and AD pathology, and the association with Alzheimer’s dementia is partially mediated through dietary choline

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Benefits of Choline in the Human Body (Perplexity AI)

Choline is an essential nutrient that plays vital roles throughout the human body, affecting everything from cellular structure to brain function. While your liver produces small amounts naturally, dietary intake is necessary to meet your body's requirements and avoid deficiency 1 2.

Cell Membrane Structure and Function

Choline serves as a crucial building block for cell membranes through its conversion to phosphatidylcholine, the most abundant phospholipid in mammalian cellular membranes 3 4. Phosphatidylcholine comprises 40-50% of the phospholipids in human cell membranes 5 and forms the phospholipid bilayer that maintains cellular integrity 3. This bilayer is self-healing and highly fluid, which is essential for proper cell function and signaling 3.

The structural role of phosphatidylcholine extends beyond basic membrane formation. It enhances the free passage of nutrients into cells while facilitating the removal of waste products, thereby optimizing cellular metabolism and energy production 3. As phosphatidylcholine levels decline with age, injury, toxic exposure, and poor nutrition, cellular homeostasis becomes compromised 3.

Neurotransmitter Synthesis and Brain Function

One of choline's most critical functions is serving as the precursor for acetylcholine, a key neurotransmitter involved in memory, mood, muscle control, and other brain functions 1 2. Acetylcholine is essential for:

• Memory and Learning : The neurotransmitter plays crucial roles in memory formation, attention, and cognitive performance 1 6

• Muscle Control : Acetylcholine is the primary neurotransmitter at neuromuscular junctions, enabling voluntary muscle movement 78

• Autonomic Function : It regulates heart rate, digestion, and other involuntary processes through the parasympathetic nervous system 7 9

Research indicates that choline supplementation can improve visuomotor performance and accuracy in targeting tasks, while also causing beneficial changes in pupil constriction that correlate with enhanced cognitive function 10.

Fetal Brain Development and Pregnancy

Choline's importance becomes particularly pronounced during pregnancy and early development. The fetus exists in a high-choline environment, with concentrations in amniotic fluid being tenfold higher than maternal blood levels 11. This elevated exposure supports critical developmental processes:

Neural Tube Formation

Higher maternal choline intake is associated with reduced risk of neural tube defects. Meta-analysis of multiple studies shows that low maternal choline intake or circulating concentrations increase the odds of neural tube defects by 36% 12.

Hippocampal Development

Choline supplementation during late pregnancy can produce lasting effects on memory and cognitive function. In animal studies, supplementation increased hippocampal progenitor cell proliferation, decreased cell death, and enhanced memory performance by up to 30% throughout the offspring's lifetime 11. Human studies have shown similar benefits, with higher maternal choline intake linked to improved attention and information processing speeds in children 13 12.

Neurogenesis and Myelination

Choline supports the rapid brain growth that occurs during the third trimester and continues until approximately age five. It provides material for myelin synthesis, which insulates nerve fibers, and supports the production of acetylcholine needed for proper brain organization and synapse formation 11.

Liver Function and Fat Metabolism

The liver is central to choline metabolism, and adequate choline intake is essential for proper hepatic function 14 15. Choline deficiency quickly leads to fatty liver disease through several mechanisms:

VLDL Production

Phosphatidylcholine is required for assembling very-low-density lipoproteins (VLDL), which transport triglycerides out of the liver. Without sufficient choline, fat accumulates in liver cells, leading to nonalcoholic fatty liver disease 14 15.

Bile Production

Choline-derived phosphatidylcholine works with bile salts as surfactants, facilitating the intestinal absorption of dietary fats 5. It also helps solubilize cholesterol for secretion in bile 14.

Methyl Group Metabolism

Choline contributes to the methylation cycle by providing methyl groups through its conversion to betaine. This process is crucial for maintaining proper levels of S-adenosylmethionine, the universal methyl donor needed for DNA methylation and other cellular processes 15 16.

Epigenetic Regulation

Choline plays a significant role in epigenetic regulation through its contribution to DNA and histone methylation 16 17. As a methyl donor, choline affects:

• Gene Expression : Dietary choline intake can modify epigenetic marks on DNA and histones, thereby influencing the expression of genes involved in development, metabolism, and disease 16

• Fetal Programming : Maternal choline intake during pregnancy affects DNA methylation patterns in the developing fetus, with lasting impacts on gene expression and health outcomes 16 18

• Disease Prevention : Proper methylation patterns supported by adequate choline intake may help prevent the development of liver cancer and other diseases 16 17

Cardiovascular Health

Choline's relationship with cardiovascular health is complex, involving both beneficial and potentially harmful pathways:

Homocysteine Regulation

Choline helps convert homocysteine to methionine through the betaine pathway, thereby reducing homocysteine levels 19 20. Elevated homocysteine is associated with increased cardiovascular disease risk, and choline supplementation can significantly reduce both fasting and post-methionine load homocysteine levels 19.

Anti-inflammatory Effects

Higher choline intake has been associated with reduced levels of inflammatory markers including C-reactive protein, interleukin-6, and tumor necrosis factor-α 20. This anti-inflammatory effect may contribute to cardiovascular protection.

Pulmonary Function

Choline is essential for producing pulmonary surfactant, a mixture primarily composed of phosphatidylcholine that enables lung elasticity and proper breathing 5. Deficiency of phosphatidylcholine in lung tissues has been linked to acute respiratory distress syndrome 5.

Recommended Intake and Deficiency

The adequate intake levels for choline vary by age and physiological state 1 21:

• Adult women: 425 mg/day

• Adult men: 550 mg/day

• Pregnant women: 450 mg/day

• Breastfeeding women: 550 mg/day

Despite its importance, most people in Western countries consume less than the recommended amounts 1 22. True deficiency is rare but can cause fatty liver disease, muscle damage, and during pregnancy, increased risk of neural tube defects and other complications 1 23.

Conclusion

Choline's benefits span virtually every aspect of human physiology, from maintaining cellular integrity and supporting brain function to enabling proper fetal development and liver metabolism. Its roles in neurotransmitter synthesis, epigenetic regulation, and methylation reactions underscore its fundamental importance to human health. Given that most people don't consume adequate amounts through diet alone, ensuring sufficient choline intake through food sources or supplementation may be crucial for optimal health outcomes 1 22.

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  1. Does Increasing Choline (Eating an Egg) Decrease Alzheimer's Risk?

Yes, emerging research suggests that increasing choline intake, including eating eggs, may help reduce Alzheimer's disease risk . Multiple studies demonstrate significant associations between choline consumption and lower dementia rates.

    1.  <strong>Key Research Findings</strong>

Recent Landmark Study : A major 2024 study published in The Journal of Nutrition followed 1,024 older adults for an average of 6.7 years and found that eating one or more eggs per week was associated with a 47% reduced risk of Alzheimer's dementia compared to those who rarely ate eggs 1 2 3. The researchers also conducted brain autopsies on 578 deceased participants and discovered that egg consumption was associated with less buildup of proteins linked to Alzheimer's disease 1.

Choline's Role : The study revealed that **39% of the protective effect from eating eggs was attributed to their choline content4 3. One large egg contains approximately 150 milligrams of choline, providing 25% of the recommended daily value 2 4.

    1.   </strong>Optimal Choline Intake for Brain Protection<strong>

• 350mg per daywas associated with the lowest risk of clinical Alzheimer's diagnosis in older adults, equivalent to about 2-3 large eggs daily 1

• Studies show that choline intake between 187-400mg per day reduces the risk of cognitive decline by approximately 50%compared to lower intakes 5

• However, very high choline intake (above 400-500mg daily) may not provide additional benefits and could potentially increase risks 6

  1.   </strong>Mechanisms of Protection<strong>
  

Acetylcholine Production: Choline serves as the precursor for acetylcholine, a crucial neurotransmitter for memory and learning. Alzheimer's patients have severely deficient acetylcholine levels, and choline supplementation helps restore this deficit 7 8.

Cell Membrane Integrity: Phosphatidylcholine, derived from choline, is essential for maintaining neuronal membrane structure and function9 10. Brain phospholipids containing choline account for 32.8% of total brain phospholipids and are critical for proper neurotransmission 9.

Methylation and Homocysteine Reduction: Choline participates in methylation processes that help reduce homocysteine levels. Elevated homocysteine is strongly associated with increased Alzheimer's risk, cognitive decline, and brain atrophy11 12 13.

Amyloid and Tau Reduction: Animal studies demonstrate that lifelong choline supplementation significantly reduces amyloid-β plaque load and decreases disease-associated microglial activation14 15.

    1.   </strong>Clinical Evidence from Human Studies<strong>

Blood Choline Levels: Research from Arizona State University found that Alzheimer's patients have significantly reduced circulating choline levels compared to healthy individuals, with the lowest levels in those with the most severe pathology 16. The study showed strong associations between low blood choline and higher accumulations of both amyloid plaques and tau tangles 16.

Cognitive Performance: A large UK Biobank study tracking 125,000 people for 12 years found that higher choline intake reduced dementia risk, with the most benefit around 400mg per day17. Another study of middle-aged and elderly Japanese adults showed that 300mg daily of egg yolk choline improved verbal memory over 12 weeks18.

    1.   </strong>Practical Recommendations<strong>

Single Egg Benefits: The research suggests that eating just one egg per week may provide significant protection, though daily consumption appears optimal based on the dosage studies 1 19.

Timing Considerations: Evidence suggests that choline supplementation is most effective when started earlier in life, as lifelong supplementation shows the greatest benefits in preventing Alzheimer's pathology 14 15.

Current Intake Gap: Most Americans fall short of optimal choline intake. More than 90% of Americans don't meet the recommended daily choline intake, with average consumption being 402mg for men and only 278mg for women 20 16.

    1.   </strong>Study Limitations and Considerations<strong>

• Many studies relied on self-reported dietary data

• Some research was funded by the Egg Nutrition Center, though findings are consistent across independent studies

• The relationship appears to be non-linear, with both very low and very high choline intake potentially being problematic 6

• More diverse population studies are needed to confirm findings across different ethnic groups

  1.   </strong>Conclusion<strong>
  

The current evidence strongly suggests that increasing choline intake through foods like eggs can help reduce Alzheimer's disease risk. The protective effect appears to be dose-dependent, with optimal benefits around 300-400mg daily - achievable through eating 2-3 eggs per day or 1 egg plus other choline-rich foods. However, even modest increases, such as eating one egg weekly, may provide meaningful protection against cognitive decline and dementia.

  1. Association Between Choline and Vitamin D

    1.   </strong>Fetal Brain Development and Prenatal Health<strong>

The most well-established connection between choline and vitamin D exists in fetal brain development. Both nutrients are essential for optimal neural development during pregnancy and are often studied together in this context 1 2. Research shows that choline, folic acid, and vitamin D are essential for fetal brain development and may be the first steps in preventing pathogenesis of psychiatric disorderslike schizophrenia and autism spectrum disorders 1 2.

    1.   </strong>Neurotransmitter Synthesis and Brain Function<strong>

A particularly significant connection exists between vitamin D and acetylcholine synthesis, where choline serves as the precursor. Vitamin D plays a direct role in acetylcholine production by regulating the enzyme choline acetyltransferase (ChAT), which converts choline into acetylcholine3 4 5 6. Studies demonstrate that:

• 1,25-dihydroxyvitamin D3 treatment results in increased choline acetyltransferase activityin specific brain regions, particularly the arcuate-median eminence and bed nucleus of the stria terminalis 5

• Vitamin D deficiency can impair cholinergic transmission by reducing ChAT activity and altering acetylcholine levels in the brain 3 4

• Vitamin D supplementation has been shown to restore altered cholinergic receptor gene expressionand normalize acetylcholinesterase activity in various neurological conditions 4

  1.   </strong>Metabolic Interactions and TMAO Production<strong>
  

Vitamin D supplementation can affect choline metabolism pathways. Research shows that vitamin D supplementation significantly increased serum levels of choline, carnitine, and related metabolites7. A study found that vitamin D supplementation caused alterations in choline metabolism, potentially reflecting the metabolic flexibility of one-carbon metabolism 8.

Additionally, vitamin D appears to influence the conversion of choline to trimethylamine N-oxide (TMAO). Studies indicate that vitamin D supplementation can reduce plasma TMAO levels, which is significant since elevated TMAO is associated with cardiovascular disease risk 8.

    1.   </strong>Phospholipid Metabolism and PEMT Pathway<strong>

    1.   </strong>Clinical Implications<strong>

Prenatal Care: Both nutrients are recommended during pregnancy, with optimal timing being pre-conception or early second trimester for choline and throughout pregnancy for vitamin D 1.

Neurological Conditions: Studies show that vitamin D supplementation can improve cholinergic transmission and cognitive function, particularly in conditions like diabetes-induced cognitive impairment and high-fat diet-induced memory problems 4 11.

Dosage Considerations: The interplay between these nutrients suggests that adequate levels of both may be necessary for optimal brain function, with vitamin D potentially enhancing the utilization of choline for neurotransmitter synthesis 6.

    1.   </strong>Research Gaps<strong>

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  1. Omega-3 and Vitamin D also decrease Dementia and Alzheimer's - VitaminDWiki

• Better cognition associated with higher Omega-3 index – Sept 2023

• Cognitive Impairment 1.8 times more likely if low Omega-3– Oct 2016

• Dementia 4.1 X high risk in those with low Vitamin D, Omega-3, etc.2 decades before (behind paywall) – Nov 2021

• Omega-3 is important for Brain Health during all phases of life – Aug 2018

• Standard Omega-3 not get past blood-brain barrier in seniors at high risk of Alzheimer’s – Patrick hypothesis Oct 2018

• Dementia 5X less likely if have good levels of Vitamin D, Omega-3 and Homocystine - July 2024

• Dementia prevented by Omega-3, Vitamin D, etc. book and video May 2024

• Alzheimer's risk factors (most of which are reduced by Vitamin D) - Jan 2025

• Consensus: Vitamin D deficiency is related to Alzheimers (9 of 10 studies) - May 2024

• Vitamin D deficiency increases risk of Dementia by 1.4 X and Alzheimer’s by 1.5 X – Meta-analysis March 2024

• Overview Alzheimer's-Cognition and Vitamin D

• Cognitive decline is 19X more likely if low vitamin D

• End of Alzheimer's videos, transcripts - many studies protocol has been very successful

• It adjusts Vitamin D , B-12, Iron, Omega-3, food, etc, and can now be done at home. $75/month .