An essential nutrient produced in small amounts by the liver and found in foods such as eggs, broccoli, beans, meat and poultry, choline is an essential component of human health. A new study explores how a lack of choline in the diet can adversely affect the body and is the missing piece in the Alzheimer’s disease puzzle.
It is estimated that over 90% of Americans do not meet the recommended daily intake of choline. Current research conducted in mice suggests that dietary choline deficiency can have severe adverse effects on the heart, liver, and other organs.
Insufficient choline is also associated with profound changes in the brain associated with Alzheimer’s disease. and pathologies involved in the development of tau tangles that condense within the body of neurons.
A new study led by Arizona State University scientists describes the pathology of normal mice deprived of dietary choline and transgenic mice deficient in choline. In both cases, dietary choline deficiency is associated with liver damage, heart enlargement, and AD mice typically associated with Alzheimer’s disease, including increased levels of plaque-forming amyloid-beta protein and disease-associated alterations in tau protein. It causes neurological changes.
This study highlights the constellation of physical and neurological changes associated with choline deficiency. Sufficient choline in the diet reduces levels of the amino acid homocysteine. Homocysteine is recognized as a neurotoxin that contributes to neurodegeneration and is important in mediating functions such as learning and memory through the production of acetylcholine.
Growing awareness of the importance of choline should encourage all adults to ensure adequate choline intake. This is especially true for those on a plant-based diet, who may have less choline in their body.
Plant-based choline-rich foods such as soybeans, Brussels sprouts, and toast can help boost choline in these cases. Inexpensive choline supplements are recommended.
Nutrients that activate the brain
Choline is required to produce acetylcholine, a neurotransmitter that plays an important role in memory, muscle control, and mood. Choline also builds cell membranes and helps regulate gene expression. Institute of Medicine established recommendations are based on evidence to prevent fatty liver disease in men. A new body of evidence suggests that the established recommended daily intakes of dietary choline for adult women (425 mg/day) and adult men (550 mg/day) may not be optimal for adequate brain health and cognition. Additionally, approximately 90% of Americans do not meet recommended levels and may not even be aware that they need choline in their daily diet.
Despite decades of research and billions of dollars of investment since the devastating disease was discovered more than a century ago, there is still no cure that can slow the progression of the disease. New research results suggest that environmental and lifestyle changes that include adequate choline may help protect the brain from Alzheimer’s disease and improve overall health.
Velázquez participates in a study by co-lead authors and NDRC researchers Nikhil Dave and Jessica Judd. The study is highly interdisciplinary and includes researchers from the ASU Biosciences Mass Spectrometry Facility and the Translational Cardiovascular Research Center at the University of Arizona School of Medicine, Phoenix.
“This collaborative effort, spanning multiple institutions and investigating the molecular processes of aging at the systems level, adds to the body of evidence that has been generated regarding the importance of dietary choline in healthy aging.
The study is published in the latest issue of the journal Aging Cell.
Prolific and mysterious killer
Alzheimer’s disease is the leading cause of dementia and the fifth leading cause of death in Americans over the age of 65. Today, Alzheimer’s disease affects 6.5 million of her in the United States alone, and by 2060 he is projected to affect nearly 14 million Americans. By this point, the cost of managing Alzheimer’s disease is expected to exceed $20 trillion, threatening healthcare infrastructure and causing immense suffering.
Accumulation of sticky protein fragments outside neurons that form amyloid-β plaques, and accumulation of abnormal forms of the protein tau (tau tangles) within neuronal cell bodies have long been recognized as signposts of Alzheimer’s disease. These brain changes are usually followed by neurodegeneration with neuronal damage and destruction. Plaques are thought to damage cell-to-cell communication in the brain, while tangles block the transport of vital nutrients essential for proper cell function and survival.
In addition to amyloid-beta plaques and neurofibrillary tangles, the disease causes increased cell death and cognitive impairment in the brain. The current study also found dysregulation of hippocampal proteins, a key structure affected in Alzheimer’s disease, that is linked to learning and memory. Both normal and AD mice showed hippocampal protein dysregulation on a choline-deficient diet, with AD models showing severe effects.
The recent dramatic increase in Alzheimer’s disease is a serious concern. While deaths from stroke, heart disease and HIV declined between 2000 and 2019, deaths from Alzheimer’s disease increased by more than 145%. In addition to the patient’s toll, Alzheimer’s disease places an immense burden on those who care for them. In 2021 alone, more than 11 million family members and other unpaid caregivers provided 16 billion hours of care.
Many factors contribute to the development of AD, from genetic predisposition to age, lifestyle and environmental influences. For reasons that remain obscure, women are at a higher risk of developing the disease.
Recent studies have identified diet as an important factor associated with preventing cognitive decline. In a previous study, Velázquez and his colleagues showed that mouse offspring showed improved spatial memory when mice were fed a high-choline diet compared to a normal choline regimen in utero. Interestingly, the beneficial effects of choline supplementation were transmitted across generations, protecting not only mice receiving choline supplementation during pregnancy and lactation, but also the subsequent offspring of these mice. It suggests a genetic modification of the gene.
A new study looks at mice between 3 and 12 months of age, which means they are in early to late adulthood. For both normal and transgenic mice exhibiting symptoms of Alzheimer’s disease, mice exposed to a choline-deficient diet showed adverse effects on weight gain and metabolism. Damage to the liver was observed through histological analysis as well as cardiac enlargement. Elevated soluble, oligomeric and insoluble amyloid beta proteins were detected, along with characteristic modifications of tau protein leading to neurofibrillary tangles in the brain.
Furthermore, choline-deficient mice performed worse on tests of exercise performance when compared with mice receiving sufficient dietary choline. Translating these findings to humans, this means that anyone predisposed to, or suffering from, Alzheimer’s disease should ensure they are getting enough choline.
The study also included a detailed look at proteins in the hippocampus, a region of the brain strongly affected by Alzheimer’s disease, and proteins detected in the blood. Dietary choline deficiency altered key hippocampal networks. These pathologies include disruption of pathways associated with microtubule function and postsynaptic membrane regulation. Both of these are essential for proper brain function. In the blood, proteins produced in the liver involved in metabolic functions were particularly dysregulated on a choline-deficient diet.
“Our research provides further support that dietary choline should be consumed daily, taking into account the needs of the body as a whole,” says Velázquez.
Ultimately, controlled human clinical trials are essential to establish choline efficacy and appropriate dosages before lifelong choline supplementation can be encouraged. The discovery offers hope that choline may become one tool in the arsenal needed to protect the brain from neurodegeneration and age-related cognitive decline.