In a new study, Biodesign researchers find that a lifelong diet for choline has the potential to prevent Alzheimer's disease (AD).
Choline is a safe and easy-to-use nutrient that is naturally present in some foods and can be used as a nutritional supplement. Lead author Ramon Velazquez and his colleagues at the ASU-Banner Center for Neurodegenerative Disease Research (NDRC) have examined whether this nutrient can alleviate the effects of Alzheimer's disease.
Earlier this year, Velazquez and his colleagues discovered the transgenerational benefits of AD-like symptoms. mice whose mothers were supplemented with choline. Recent work extends this line of research by examining the effects of choline administered in adulthood rather than in fetal mice.
The study focuses on female mice raised to develop AD-like symptoms. Given the higher prevalence of AD in human women, the study seeks to identify findings in female mice. The results show that when these mice receive high choline in their lifelong diet, they show improvements in spatial memory compared to those receiving normal choline regimen.
In particular, the findings in July 201
Intriguingly, the beneficial effects of lifelong choline supplementation decrease microglial activation. Microglia are specialized cells that rid the brain of harmful debris. Although they naturally happen to keep the brain healthy, if they are overactivated, brain inflammation and neuronal death will be common symptoms of AD.
Observed reductions in disease-associated microglia present in a variety of neurodegenerative diseases offer new exciting studies and provide treatments for a wide range of disorders, including traumatic brain injuries, multiple sclerosis, and Parkinson's disease.
The results appear in the current issue of Aging Cell .  Complementing the brain with additional choline
Choline acts to protect the brain from Alzheimer's disease in at least two ways, both of which were investigated in a new study. First, choline blocks the production of amyloid-beta plaques. Amyloid-beta plaques are a distinctive pathology observed in Alzheimer's disease.
Second, the addition of choline reduces the activation of microglia. Overexpression of microglia causes brain inflammation and can ultimately lead to neuronal death, thus compromising cognitive function. Choline supplementation reduces microglial activation, offering further protection against AD damage.
The mechanical reduction of microglial activation is due to a change in two key receptors, the alpha7 nicotinic acetylcholine and the Sigma-1 receptor. A new report this year found that choline could act as a Sigma-1 receptor agonist. These results confirm that, throughout life, the addition of choline can alter Sigma-1 receptor expression, thereby enhancing microglial activation. (The agonist is a substance that activates a receptor.)
The devastating decline
It is well known in the scientific community that Alzheimer's disease causes brain damage long before the clinical symptoms become apparent. And once these symptoms have been identified, it's too late – the disease has become irreversible. In addition to causing disorientation and memory loss, the disease causes loss of motor control in those affected.
Currently, about 6 million individuals live with AD in the United States, and the disease is expected to affect 14 million Americans in the next four decades. The economic costs of managing Alzheimer's disease are expected to exceed $ 20 trillion over the same period.
In order to develop more effective treatment, we must first understand the disease itself, which is one of the highest commandments that modern medicine is facing today.
Women are at particularly high risk of developing Alzheimer's disease. This study shows that simply adding choline to a lifelong diet can reduce AD pathology in those who are most affected by the disease. In addition, these results are also reflected in other neurodegenerative sufferings in which activated microglia grow, says Velazquez.
Dietary Choline Guidelines
Previous studies on Alzheimer's have shown that there is no single factor in play. Rather, there are numerous factors that are thought to contribute to the development of the disease, including genetics, age and lifestyle. In addition, studies suggest that diet can have a significant effect in increasing or decreasing the risk of cognitive decline.
A recent report suggests that plant-based diets can be determinative due to the lack of important nutrients, including choline. Another recent report found that an increase in UK dementia may be associated with a lack of lifelong choline recommendations. In fact, as of August 2019, AD and other forms of dementia are now the leading cause of death in England and Wales.
The present established adequate level of choline intake for adult women (> 19 years of age) is 425 mg / day, and 550mg / day for adult men. Converging information shows that even the current recommended daily intake (RDI) may not be optimal for the proper aging process, especially for women. This is appropriate given the higher incidence of AD seen in women. This suggests that supplemental choline in the diet may be helpful in preventing neuropathological changes related to the aging brain.
The allowable upper limit (TUL) for choline is unlikely to cause side effects for older women and men (> 19 years) is 3500mg / day, which is 8.24 times higher than the 425 mg / day recommendation for women and 6.36 times the 550 mg / day recommendation for men. "The choline supplemented diet was only 4.5 times that of RDI, which is well below TUL, which makes it a safe strategy," Velazquez says.
Choline can be found in various foods. According to the USDA, high levels of choline are found in chicken liver (3oz; 247mg), eggs (1 large egg yolk; 147mg), beef steak (3oz; 55mg), wheat germ ( 1oz toast; 51mg), milk (8oz; 38mg) and Brussels sprouts (1/2 cup; 32mg). In addition, vitamin supplements containing choline, such as choline bitartrate and choline chloride, are widely available at affordable prices. Choline-containing vitamin supplements are especially suitable for those on a plant-based diet.
Effects of choline
All plant and animal cells need choline to maintain their structural integrity. It has long been recognized that choline is particularly important for brain function.
The human body uses choline to produce acetylcholine, a neurotransmitter responsible for memory function, muscle control and mood. Choline is also used to build cell membranes and plays a vital role in regulating gene expression. In addition, a new report in January 2019 finds that choline acts as an agonist at Sigma-1 receptors, which are implicated in the pathogenesis of AD.
In this study, researchers used a water maze to determine whether mice had AD-like symptoms. lifelong supplemental choline showed improvements in spatial memory. This was indeed found to be the case, and subsequent study of mouse tissue derived from the hippocampus, a brain region known to play a central role in memory formation, confirmed changes in toxic amyloid-beta and decreased microglial activation. which reduces brain inflammation.
Due to changes in key microglial receptors induced by choline, behavioral improvements may be due to reduced microglial activation. "We have found that, throughout life, the choline supplementation alters alpha7 nicotinic acetylcholine and the Sigma-1 receptor, which can reduce the activation of activated microglia in patients," Velazquez said. These receptors regulate the CNS immune response and dysregulation contributes to the pathogenesis of AD.
The significance of the study establishes the beneficial effects of nutrient supplementation on women throughout life. "Our work is a wonderful complement to the recent work showing the benefits of male AD mice in a lifelong choline supplementation regimen." "No one has shown the lifelong benefits of choline supplementation in female AD mice." "This is new to our work."
Choline is an attractive candidate for the prevention of AD, as it is considered a very safe alternative compared to many pharmaceuticals. "At 4.5x RDI (recommended daily intake), we are well below the acceptable upper limit, making this a safe preventative therapeutic strategy."
Although the results improve understanding of the disease, the authors suggest that clinical trials will need to confirm whether choline can be used as a viable treatment in the future.
The recommended switch to plant-based diets risks worsening nutrient deficiencies in the brain
Ramon Velazquez et al., HOL throughout life alleviates the pathology of Alzheimer's disease and associated cognitive deficits by attenuating microglial activation, Aging Cell (2019). Doi: 10.1111 / acel.13037
Arizona State University
The Common Nutrient Supplement May Be the Answer to Fight Alzheimer's Disease (2019, September 27)
retrieved September 27, 2019
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