Current nutrient supplementation could help fight Alzheimer's disease

In a new study, Biodesign researchers revealed that a choline-based diet had the potential to prevent Alzheimer's disease.

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 ASU-Banner's Center for Research on Neurodegenerative Diseases (BDSN) examined whether this nutrient could mitigate the effects of Alzheimer's disease.

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

The study focuses on female mice bred to develop symptoms similar to those of AD. Given the higher prevalence of Alzheimer's disease in women, the study aimed to establish the results in female mice. The results showed that when these mice receive a diet rich in choline throughout their life, they exhibit improvements in spatial memory compared to those receiving a normal choline diet.

Notably, findings published in July 2019 from a group in China have highlighted the benefits of lifetime choline supplementation in male mice exhibiting symptoms similar to those of the disease. "Our results reproduce the results of this group in women," said Velazquez.

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

Observed reductions in disease-related microglia, present in a variety of neurodegenerative diseases, offer exciting new avenues of research and suggest ways to treat a wide range of disorders, including traumatic brain injury, multiple sclerosis and Parkinson's disease. .

The results appear in the current issue of the journal Aging cell.

Complete the brain with additional choline

Choline protects 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 beta amyloid plaques. The beta-amyloid plaques are the characteristic pathology observed in Alzheimer's disease.

Secondly, choline supplementation reduces the activation of microglia. Overactivation of microglia causes inflammation of the brain and may eventually lead to neuronal death, compromising cognitive function. Choline supplementation reduces the activation of microglia, providing additional protection against the ravages of AD.

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

The devastating decline

In the scientific community, it is well known that Alzheimer's disease causes brain damage long before clinical symptoms become evident. And once these symptoms are identified, it is too late, the disease has become irreversible. In addition to causing disorientation and memory loss, the disease results in a loss of motor control in those affected.

In the United States, about 6 million people are living with Alzheimer's disease and the disease is expected to affect 14 million Americans over the next four decades. Economically, the costs associated with the management of Alzheimer's disease are expected to exceed $ 20 trillion over the same period.

To develop more effective treatments, we must first understand the disease itself, which is one of the most important orders that modern medicine is currently facing.

Women are at a particularly increased risk of developing Alzheimer's disease. This study shows that simply adding choline to the diet throughout life can reduce the pathology of AD in those most affected by the disease. In addition, these findings have implications for other neurodegenerative conditions in which activated microglia is endemic, Velazquez states.

Guidelines for food choline

Previous research regarding Alzheimer's disease has shown that there was not one factor involved. Rather, a multitude of factors are believed to contribute to the development of the disease, including genetics, age and lifestyle. In addition, studies suggest that diet can have a significant effect on increasing or reducing the risk of cognitive decline.

A recent report suggested that herbal diets could be crucial because of the lack of important nutrients, especially choline. Another recent report has shown that the increase in the number of cases of dementia in the UK may be associated with a lack of recommendations regarding the presence of choline in the diet throughout life. In fact, since August 2019, Alzheimer's disease and other forms of dementia are now the leading cause of death in England and Wales.

The current level of choline consumption established for adult women (> 19 years) is 425 mg / day and 550 mg / day for adult men. A convergent data set indicates that even the currently recommended daily dose may not be optimal for a good aging process, especially for women. This is relevant given the higher incidence of AD in women. This suggests that an additional choline diet could be beneficial in preventing neuropathological changes associated with aging of the brain.

The tolerable upper limit (TUL) of choline is unlikely to cause adverse effects in adult women and men (> 19 years) is 3500 mg / day, 8.24 times more than the 425 mg recommendations / day for women and 6.36 times higher than the 550 mg / day recommendation for men. "Our choline supplement diet was only 4.5 times the RDI, which is well below the TUL, making it a safe strategy," Velazquez said.

Choline can be found in various foods. According to the United States Department of Agriculture (USDA), high choline levels are found in chicken liver (3 oz, 247 mg), eggs (1 large egg with yellow, 147 mg), grass-fed beef steak (3 oz, 55 mg), wheat germ (1 oz toast, 51 mg), milk (8 oz, 38 mg) and Brussels sprouts (1/2 cup, 32 mg ). In addition, vitamin supplements containing choline, for example choline bitartrate and choline chloride, are widely available at affordable costs. Vitamin supplements containing choline are especially useful for people who are following 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 especially important for brain function.

The human body uses choline to produce acetylcholine, a neurotransmitter responsible for the functioning of memory, 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 published in January 2019 revealed that choline acts as a receptor agonist Sigma-1, which is involved in the pathogenesis of Alzheimer's disease.

In this study, the researchers used an aquatic maze to determine whether mice exhibiting symptoms similar to Alzheimer's disease and receiving additional choline throughout life exhibited improvements in spatial memory. It turned out that this was indeed the case, and the subsequent examination of mouse tissue extracted from the hippocampus, a brain region known to play a central role in memory formation, confirmed changes in the beta-amyloid toxic substance and reductions in activation of microglia inflammation.

Due to key receptor alterations of choline-induced microglia, behavioral improvement can be attributed to reduced activation of microglia. "We found that lifetime choline supplementation altered the receptors for alpha7 nicotinic acetylcholine and Sigma-1 receptor, which could have resulted in the reduction of activated microglia associated with the disease," said Velazquez. These receptors regulate the immune response of the CNS and their deregulation contributes to the pathogenesis of AD.

The importance of the study establishes the beneficial effects of nutrient supplementation in women throughout life. "Our work perfectly complements recent work showing the benefits in male MA mice for a lifetime choline supplementation regimen." "Nobody has shown the lifetime benefits of choline supplementation in female AD mice." "It's what's new in our work."

Choline is an attractive candidate for the prevention of AD because it is considered a very safe alternative to many pharmaceutical products. "At 4.5 times the RDI (recommended daily intake), we are well below the tolerable upper limit, making it a safe preventive therapeutic strategy."

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