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Common nutrient supplementation may hold the answers to combating Alzheimer's disease



Common nutrient supplementation may hold the answers to combatting Al

Results showed that when these mice are exposed to Alzheimer's disease with high choline levels throughout their lives, they exhibit spatial memory improvements compared to those receiving a normal choline regimen. Credit: Shireen Dooling: Biodesign Institute at Arizona State University

In a new study, Biodesign researchers indicate that a lifelong diet of choline holds the potential to prevent Alzheimer's disease (AD).

Choline is a safe and easy-to-administer nutrient that is naturally present in some foods and can be used as a dietary supplement. Lead author Ramon Velazquez and colleagues at the ASU-Banner Neurodegenerative Disease Research Center (NDRC) looked into whether this nutrient could alleviate the effects of Alzheimer's.

Earlier this year, Velazquez and colleagues found transgenerational benefits of AD-like symptoms in mice whose mothers were supplemented with choline. The latest work expands this line of research by exploring the effects of choline administered in adulthood rather than in fetal mice.

The study focuses on female mice bred to develop AD-like symptoms. Given the higher prevalence of AD in human females, the study sought to establish the findings in female mice. Results showed that when these mice were given high choline in their diet throughout their lives, they exhibited improvements in spatial memory compared with those receiving a normal choline regimen.

Notably, findings published in July 2019 from a group in China found benefits of lifelong choline supplementation in male mice with AD-like symptoms. "Our results nicely replicate findings from this group in females," Velazquez says.

Intriguingly, the beneficial effects of lifelong choline supplementation reduce microglia activation. Microglia are specialized cells that rid the brain of deleterious debris. Although they naturally occur to keep the brain healthy, if they are overactivated, brain inflammation and neuronal death, common symptoms of AD, will occur.

The observed reductions in disease-associated microglia, which are present in various neurodegenerative diseases, offer exciting new avenues of research and suggest ways of treating a wide range of disorders, including traumatic brain injuries, multiple sclerosis and Parkinson's disease.

The findings appear in the current issue of the journal Aging Cell.

Supplementing the brain with additional choline

Choline acts to protect the brain from Alzheimer's disease in at least two ways, both of which are explored in the new study. First, choline blocks the production of amyloid-beta plaques. Amyloid-beta plaques are the hallmark pathology observed in Alzheimer's disease.

Secondly, choline supplementation reduces microglia activation. Over-activation of microglia causes brain inflammation and can eventually lead to neuronal death, thereby compromising cognitive function. Choline supplementation reduces microglia activation, offering further protection from AD ravages.

Mechanistically, the reductions in microglia activation are driven by alteration of two key receptors, the alpha7 nicotinic acetylcholine and the Sigma-1 receptor. A new report this year found that choline can act as an agonist for Sigma-1 receptors. These results confirm that lifelong choline supplementation can alter the expression of the Sigma-1 receptor, which thereby attenuates microglia activation. (An agonist is a substance that activates a given receptor.)

The devastating decline

In the scientific community, it is well understood that Alzheimer's disease causes damage to the brain long before clinical symptoms become apparent. And once these symptoms are 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 who are affected.

Approximately 6 million individuals are living with AD in the U.S. currently, and the disease is projected to affect 14 million Americans in the next four decades. Economically, the costs associated with managing Alzheimer's are expected to exceed $ 20 trillion at the same time span.

Common nutrient supplementation may hold the answers to combatting Al

Microglia are specialized cells that work to clear away debris in the brain and perform other essential duties. These cells typically become dysregulated in Alzheimer's disease (AD), leading to inflammation and neuronal death. Intriguingly, the beneficial effects of lifelong choline supplementation reduce the activation of microglia in mice bred to develop AD-like symptoms. The choline-rich diet has been shown to improve cognitive function. Credit: Arizona State University

To develop more effective treatments, we first need to understand the disease itself, which is one of the tallest orders facing modern medicine today.

Women are at particular increased risk of developing Alzheimer's disease. This study shows that the simple addition of choline to the diet throughout life may reduce AD ​​pathology in those most affected by the disease. Additionally, these results have implications for other neurodegenerative afflictions where activated microglia are rampant, says Velazquez.

Guidelines for dietary choline

Prior research regarding Alzheimer's has indicated that there is no factor at play. Rather, a multitude of factors that are believed to contribute to the development of the disease, including genetics, age and lifestyle. Additionally, studies suggest that diet can have a significant effect on increasing or decreasing the risk of cognitive decline.

A recent report suggested that plant-based diets may be determinant due to a lack of important nutrients, including choline. Another recent report found that an increase in cases of dementia in the United Kingdom may be associated with a lack of recommendations for choline in the diet throughout life. In fact, as of August 2019, AD and other forms of dementia are now the leading cause of death in England and Wales.

The current established adequate intake of choline for adult women (> 19yrs of age) is 425mg / day, and 550mg / day for adult men. A converging line of evidence indicates that even the current recommended daily intake (RDI) may not be optimal for a proper aging process, especially in women. This is relevant given the higher incidence of AD seen in women. This suggests that additional choline in the diet may be helpful in preventing neuropathological changes associated with aging brain.

The tolerable upper limit (TUL) of choline unlikely to cause side effects for adult females and males (> 19yrs of age) is 3500mg / day, which is 8.24 times higher than the 425mg / day recommendation for females and 6.36 times higher than 550mg / day recommendation for males. "Our choline supplemented diet was only 4.5 times the RDI, which is well below the TUL and makes this a safe strategy," Velazquez says.

Choline can be found in various foods. According to the United States Department of Agriculture (USDA), high levels of choline are found in chicken liver (3oz; 247mg), eggs (1 large egg with yolk; 147mg), beef grass-fed steak (3oz; 55mg), wheat hot (1oz toast; 51mg), milk (8oz; 38mg), and Brussel sprouts (1/2 cup; 32mg). Additionally, vitamin supplements containing choline, for example choline bitartrate and choline chloride, are widely available at affordable costs. The vitamin supplements containing choline are particularly relevant for those on plant-based diets.

Effects of choline

All plant and animal cells require 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. Additionally, a new report in Jan 2019 found that choline acts as an agonist for Sigma-1 receptors, which are implicated in AD pathogenesis.

In this study, researchers used a water maze to determine whether mice with AD-like symptoms who received lifelong supplemental choline exhibited improvements in spatial memory. It was found that this was indeed the case, and subsequent examination of mouse tissue extracted from the hippocampus, a brain region known to play a central role in memory formation, confirmed changes in toxic amyloid-beta and reductions in microglia activation, which reduces brain function. inflammation.

Due to alterations of key microglia receptors induced by choline, improvements in behavior may be attributed to reduced microglia activation. "We found that lifelong choline supplementation altered the alpha7 nicotinic acetylcholine and Sigma-1 receptor, which may have been associated with reduced activation of associated microglia," Velazquez said. These receptors regulate CNS immune response and their dysregulation contributes to AD pathogenesis.

The study's significance establishes the beneficial effects of nutrient supplementation on females throughout life. "Our work nicely complements recent work showing benefits in male AD mice on a lifelong choline supplementation regimen." "No one has shown the lifelong benefits of choline supplementation in female AD mice." "That's what's new about our work."

Choline is an attractive candidate for AD prevention as it is considered a very safe alternative, compared to many pharmaceuticals. "At 4.5 times the recommended daily intake of RDI, we are well under the tolerable upper limit, making this a safe preventive therapeutic strategy."

Although the results improve understanding of the disease, the authors suggest that clinical trials will be necessary to confirm whether choline can be used as a viable treatment in the future.


Suggested move to plant-based diets risks worsening brain health nutrient deficiency


More information:
Ramon Velazquez et al, Lifelong choline supplementation ameliorates Alzheimer's disease pathology and associated cognitive deficits by attenuating microglia activation, Aging Cell (2019). DOI: 10.1111 / acel.13037

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