Common Nutrient Supplementation May Hold The Answers To Combating Alzheimer's Disease

Summary:
In a new study, researchers reveal that a lifelong dietary regimen of choline holds the potential to prevent Alzheimer's disease (AD).

In a new study, Biodesign researchers reveal that a lifelong dietary regimen 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 his 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 are given high choline in their diet throughout life, they exhibit 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 by this group in females," Velazquez says.

Intriguingly, the beneficial effects of lifelong choline supplementation reduce the activation of microglia. 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 broad 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 the activation of microglia. Over-activation of microglia causes brain inflammation and can eventually lead to neuronal death, thereby compromising cognitive function. Choline supplementation reduces the activation of microglia, offering further protection from the ravages of AD.

Mechanistically, the reductions in microglia activation are driven by alteration of two key receptors, the alpha7 nicotinic acetylcholine and 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 harm to the brain long before clinical symptoms are made 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 causes loss of motor control in those who are afflicted.

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

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 a particular increased risk of developing Alzheimer's disease. This study shows that the simple addition of choline in 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 concerning Alzheimer's has indicated that there is no one 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 in increasing or lowering the risk of cognitive decline.

A recent report suggested that plant-based diets may be determinantal due to the lack of important nutrients, including choline. Another recent report found that the 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 level 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 diet may be beneficial in preventing neuropathological changes associated with the 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 the 550mg/day recommendation for males. "Our choline supplemented diet regimen 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 germ (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 who are 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 functioning memory, muscle control and mood. Choline also is 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 the mice with AD-like symptoms that 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 inflammation.

Due to alterations of key microglia receptors induced by choline, the 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 resulted in the reduction of diseased associated activated microglia," Velazquez said. These receptors regulate CNS immune response and their dysregulation contributes to AD pathogenesis.

The study's significance establishes beneficial effects of nutrient supplementation in 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 lifelong benefits of choline supplementation in female AD-mice." "That's what is novel about our work."

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

Although the results improve the 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.

Source:
Materials provided by Arizona State University. Original written by Richard Harth. Note: Content may be edited for style and length.

Journal Reference:
Ramon Velazquez, Eric Ferreira, Sara Knowles, Chaya Fux, Alexis Rodin, Wendy Winslow, Salvatore Oddo. Lifelong choline supplementation ameliorates Alzheimer’s disease pathology and associated cognitive deficits by attenuating microglia activation. Aging Cell, 2019; DOI: 10.1111/acel.13037

ScienceDaily,         27 September 2019. 

source: www.sciencedaily.com

These Are The Supplements Health Experts Actually Use

Rule number one: ignore hype.

Taking supplements you don't need can be dangerous.

Flick through social media and you'll come across countless supplements that people swear by -- turmeric pills, maca pills, goji berry juice powder, spirulina, kale powder -- you name it.

With so many supplements out there which are simply gimmicks, it's tricky knowing the good ones from the useless ones.

Well, we asked four health experts which supplements they actually use and recommend, and importantly, in what circumstance you truly require them.

According to Alexandra Parker and Anna Debenham, accredited practising dietitians from The Biting Truth, the first and best way to get nutrients is from your food.

"As dietitians who focus on wholefoods for optimal nutrition and wellbeing, vitamins and micronutrient supplementation are not generally our initial recommendation," Parker told The Huffington Post Australia.
Get your nutrients from whole foods first, then supplement if required.
"Food first, always. Food provides vitamins in the most biologically available form, in the right quantities and combined with other complementary nutrients."

"We're big believers that if you're otherwise healthy, a healthy eating pattern should never be replaced by a supplement. More and more often we're seeing people who are eating a poor diet, drinking and smoking, and believe everything will be okay if they take a supplement."

Pharmacist and personal trainer Holly Vogt, The Fit Pharmacist, agrees.

"Vitamin supplements should not be used as a substitute for a balanced diet and if you do take them, make sure you do not exceed your daily requirement. Choosing a good health supplement should be an informed and wise decision," Vogt said.

Food first, always. Food provides vitamins in the most biologically available form, in the right quantities and combined with other complementary nutrients.

Although supplements may be marketed as 'magic bullets', unfortunately they don't provide equal nutrients to those found in foods, nor do they counteract a poor diet.

"A piece of fresh fruit, for example, contains antioxidants, phytochemicals, fibre and many other nutrients that do not make it into the vitamin jar but play a huge role in our health," Debenham told HuffPost Australia.

"Saying that, there is a time and a place for supplements and there's good evidence to suggest that if a vitamin or mineral supplement replaces a deficiency, it will have beneficial outcomes. But aside from a few specific groups of people and situations, most people who eat a balanced diet have no need for supplementation."

Who needs supplementation?

The main instances and stages of life where people may need to genuinely supplement is when food alone is simply not enough to meet an individual's nutrient needs, and supplementation becomes integral to that person's wellbeing. Some examples include:

• Those trying to conceive and pregnant women (one month prior to conception and three months after) -- folate has been shown to reduce risk of neural tube defects.
• People on a strict vegan or vegetarian diet, and elderly people who may be eating poorly and/or absorbing less from their food -- iron, and vitamin B12 as this is found almost exclusively in animal products.
• People with an allergy or intolerance such as lactose intolerance -- calcium
• Autoimmune disease e.g. Crohn's disease, cystic fibrosis or coeliac disease -- supplementation may be required at some stage to correct any nutrient deficiencies.
• People who did not receive enough sunlight (e.g. bed bound, elderly, covered/veiled women and men) -- vitamin D
• Following a course of antibiotics -- probiotics may be beneficial in restoring gut health after a round of antibiotic treatment.
• People with specific hormonal imbalances such as PCOS.
• - Parker and Debenham.

"It is important to note that we all have specific nutritional requirements and health concerns at different stages of life, and it is ideal to choose supplements that target those specific needs," Vogt said.

So, how do you tell when you need to supplement?

"If you are fatigued, training hard, have a restricted diet or limited food options available, say, when you are travelling, this is a good time for supps," celebrity trainer Tegan Haining said.

"When it comes to supplements, it's often difficult to decipher which protein powder, omega 3 oil or multivitamin to trust. It's very important to understand that supplements should not be a free-for-all," Parker explained.

These Are The Supplements Health Experts Actually Recommend

"It's best to avoid going to the supermarket or searching online when you don't know what you're looking for or if you're self-diagnosing.

"Blood tests can be useful, however are not always necessary. We highly recommend speaking to your doctor or accredited practising dietitian to determine your need for supplementation."

On top of this, not all supplements are required to be taken long term and dosages will vary depending on your specific needs.

"Some supplements have adverse effects, like toxicity or interference with nutrient absorption when taken in excess. For example, vitamin A, B or zinc," Parker said.

A few key things to consider when purchasing supplements:

• Start out with the low dosage recommendation first and increase as required.
• Look for supplements without added fillers, colours or unnecessary ingredients.
• Think of supplementation as an investment to your health and always choose quality. Try not to choose a product for its logo, price or marketing.
• Ensure you continue to eat real food.

- Parker and Debenham.

Here are five supplements health experts actually use.

1. Fish oil

"One of the key nutrients many of us don't get enough of is long chain omega 3 fats (which are found naturally in oily fish, for example, salmon)," Debenham told HuffPost Australia.
"There is solid evidence to show that omega 3 fatty acids are necessary for a healthy heart and brain, and play a role in reducing inflammation throughout the body."

Fish oil is rich in omega 3 fatty acids which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

"We cannot produce these in our bodies so it is essential that we receive them through our diet or supplementation," Vogt said. "Ensure that you choose a supplement with a high concentration of EPA and DHA, and one that has purity and sustainability certifications."
"I also like cod liver oil tablets, which are high in Vitamin D and A," Haining added.

Flaxseeds, flaxseed oil, walnuts and chia seeds are other good sources of omega 3s.

2. Probiotics
Probiotics are 'good' bacteria that line our digestive tracts and support our body's ability to absorb nutrients and fight infection.

"I always take a probiotic to ensure my gut health," Haining said.
"There is mounting scientific evidence to show that the health of our gut directly affects our immune system. Taking a daily probiotic can be a simple way to help keep your gut healthy and your immune system strong," Parker said.

"Whether you take it as a capsule, drink or powder, the choice is yours. If you've taken a course of antibiotics, supplementing with probiotics will also be beneficial to your gut."

It's important to note that there are different types of strains of probiotics, Vogt explained.

"Certain strains of probiotics support immunity, others digestion, and some even help to regulate weight and balance hormones," Vogt said.

Kombucha, yoghurt, kefir, sauerkraut, miso and tempeh all contain probiotics.

3. Vitamin D
Vitamin D is important for strong bones, muscular and overall health.

"Vitamin D is a fat soluble nutrient and is one of the 24 micronutrients essential for human survival. Due to the increasing rates of vitamin D deficiency and the implications, supplementation is encouraged if optimal levels are not present in the body," Vogt said.

"Most of us probably get enough vitamin D from the sun during the summer months (you only need about 15-20 mins of exposure). However, during winter, if you tend to spend a lot of time indoors, some of us may benefit from a vitamin D supplement," Parker added.

4. Magnesium
Magnesium is an important nutrient which plays a role in hundreds of enzymatic bodily reactions, including metabolising food, synthesis of fatty acids and proteins, and transmission of nerve impulses.

"Magnesium is also great to take in the evening for a better night's sleep and managing stress levels," Haining said.

5. Protein
While most people can obtain adequate protein through their diet (it's found in both plant-based foods and meat), select population groups can benefit from protein supplementation -- namely athletes or those who have an intense training regime.

"When it comes to muscle gain and fat loss, protein is the king of nutrients. Protein has been proven to help weight loss by boosting metabolism and reducing hunger and appetite," Vogt said.

"Whey protein is ideal, however if you have issues with lactose intolerance, then plant-based proteins are still highly effective."

By Juliette Steen   10/01/2017

source: www.huffingtonpost.com.au