Dietary Choline

Biodesign researchers at the Arizona State University - Banner Neurodegenerative Disease Research Center (NDRC) looked into whether the nutrient choline could alleviate the effects of Alzheimer's by studying AD mice.

 

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.

 

Studies in the AD mice found that choline acts to protect the brain from Alzheimer's disease in at least two ways. First, choline blocks the production of amyloid-beta plaques. Second, choline supplementation reduces the activation of microglia, which when overactive can cause death of brain cells.

From a human perspective, the authors noted that while no one factor determines the cause or clinical course of Alzheimer's, a recent report found that the increase in cases of dementia in the United Kingdom may be associated with a lack of choline in the diet throughout life. Another report suggested that plant-based diets may be detrimental due to the lack of important nutrients, including choline.

 

The current established adequate intake level of choline for adult women is 425mg/day, and 550mg/day for adult men. This recommended daily intake (RDI) may not be optimal, especially in women, given the higher incidence of AD seen in women. This suggests that additional choline in diet may be beneficial in preventing harmful changes associated with the aging brain.

 

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 Brussels sprouts (1/2 cup; 32mg).

 

The authors further noted that choline is an attractive candidate for prevention of AD, as it is considered a very safe alternative compared with many pharmaceuticals. "At 4.5 X the RDI, we are well under the tolerable upper limit, making this a safe preventive therapeutic strategy."

 

Arizona State University. "Common nutrient supplementation may hold the answers to combating Alzheimer's disease." ScienceDaily. www.sciencedaily.com/releases/2019/09/190927122526.htm (accessed November 27, 2019).

Could it be the Micobiome?

More and more evidence is piling in about the effect of the microbiome on our health, and in this entry, on brain disorders. It should be noted that while the microbiome is often referred to as in the gut, it exists in many other body parts, an example being our skin.

IBS

An article published in the US version of the Guardian asked if the microbiome is the key to health and happiness. it was reported that "The gut microbiome is a vast ecosystem of organisms such as bacteria, yeasts, fungi, viruses and protozoans that live in our digestive pipes, which collectively weigh up to 4.4 lbs. (heavier than the average brain). It is increasingly treated by scientists as an organ in its own right. Each gut contains about 100 trillion bacteria, many of which are vital, breaking down food and toxins, making vitamins and training our immune systems".The article also noted that "eight years ago, an investigation into irritable bowel syndrome drew (his)  gaze towards the gut. Like people with depression, those with IBS often report having experienced early-life trauma, so in 2009, John Cryan and his colleagues set about traumatising rat pups by separating them from their mothers. They found that the microbiome of these animals in adulthood had decreased diversity".

Depression

In work done at the Children's Hospital of Phildelphia it was recently reported that microbiome transplants affected depression in rats (one has to kind of wonder how we really know rats are depressed). "In rats that show depressive-type behavior in a laboratory test, we found that stress changes their gut microbiome -- the population of bacteria in the gut," said study leader Seema Bhatnagar, PhD, a neuroscientist in Department of Anesthesiology and Critical Care at Children's Hospital of Philadelphia (CHOP). "Moreover, when we transplanted bacteria from those stress-vulnerable rats into rats that had not been stressed, the recipient animals showed similar behavior."

Alzheimer's

Of course it was inevitable that the linking of Alzheimer's to the microbiome would need to be studied. Sure enough, this December past, the University of Chicago announced that Sangram Sisodia, Ph.D. will be doing  a research study that "will investigate the roles of the gut and brain microbiome on Alzheimer's disease and its related symptoms in humans and mice, particularly their interactions with immune cells and genes, and influence of the blood-brain barrier on these processes"

There will undoubtedly be many more studies to come on how the microbiome affects all aspects of our lives. There will be many surprising and mind shattering results that will change the way we understand disease and advance medical diagnosis and treatment. This is just the tip of the iceberg. And yes, it may very well be the key to our health and happiness (and unfortunately to disease and sadness).

"Is your gut microbiome the key to health and happiness?"Amy Fleming. The Guardian. Nov 6, 2017. https://www.theguardian.com/lifeandstyle/2017/nov/06/microbiome-gut-health-digestive-system-genes-happiness

Children's Hospital of Philadelphia. "Transplanting gut bacteria alters depression-related behavior, brain inflammation in animals: Knowledge of stress biology may eventually yield bacterial treatments for psychiatric disorders." ScienceDaily. www.sciencedaily.com/releases/2019/05/190506163642.htm (accessed May 7, 2019).

 https://www.uchicagomedicine.org/forefront/microbiome-articles/2018/december/neuroscientist-receives-grant-to-study-microbiome-and-alzheimers

Alzheimer's Research Caveats

Alzheimer's research is in the news more than ever as cultural and political factors enter the discussion. AD is such a terrible, incurable process, and affects so many families, that it is not surprising that the goal to find a cure is accelerating at a rapid pace.

One great example is in 2018 Bill Gates announced that a coalition of philanthropists have committed  $30 million for research on promising and innovative ideas to diagnose the early onset of AD before symptoms occur. The designation is the Diagnostics Accelerator fund. This approach is probably the most promising, as it known that whatever causes the onset of AD seems to occur 10-20 years prior to symptoms.

The other approach of research is the development of drugs and associated clinical trials that attempt to arrest, cure (or prevent)  AD. Over the years this has been largely ineffective. One emerging consensus is that once changes take place in the brain they are irreversible, so drugs won't work. Another is that treatments are begun too late in the course of the disease i.e- symptoms have already developed. Both are probably correct.

Yet research continues, mostly centered around amyloid, which is often associated with AD. Some new research is about tau. No meaningful positive results have occurred even as billions of dollars are spent on AD research. This blog has attempted to highlight some of these issues in previous posts.

One problem plaguing all medical research, including AD, is the not usually talked about conflicts of interest. Too often articles are published, even in prestigious medical journals, touting the latest and greatest drug, only to be proven inadequate upon further and/or independent testing. Many published researchers are paid by the pharmaceutical industry to study drugs in development. Unfortunately, some researchers are dependent on the largess of drugs firms for future funding and may not be as objective as one might  expect. The worst thing is that many times the conflict is not revealed by the researchers, so the public has no way of knowing.  Conflicting results from different researchers can be confusing,

Now the latest theories about cause and effect involve infectious diseases. More will come about this in future blogs. So, at this stage, we still seem to be floundering. Lots of thoughts, lot of money, lots of frustration. Where will it lead? AD is indeed very complicated.



https://www.medscape.com/viewarticle/899446

Gum Disease - the Root Cause of AD?

We are in EXCITING times.

• It is quite possible that we may now know a cause of AD.
• It is quite possible that we may have finally found an effective treatment.

A research paper* published just a few days ago reveals the bacteria, P. gingivali, which causes gingivitis of the gums, may be a cause of AD. Furthermore, it suggests that treating and/or preventing P. gingivali infections may very well reverse or prevent AD.

The findings include that P. gingivali is found in the associated parts of the brain of people who have AD. A toxin secreted by the bacteria (gingipain) is present in the amyloid and tau plaques associated with AD. This toxin destroys neurons (nerve cells) and causes protein damage. It is proposed that chronic, low-level inflammation of the brain caused by P. gingivali can lead to brain changes that cause AD. 

The article points out that "P. gingivalis is mainly found during gingival and periodontal infections; however, it can also be found at low levels in 25% of healthy individuals with no oral disease. Transient bacteremia of P. gingivalis can occur during common activities such as brushing, flossing, and chewing, as well as during dental procedures". Bacteremia is when bacteria get in the bloodstream, which explains how it can settle in brains. The bacteria has also been found in the spinal fluid of AD patients.

Antibiotics were used to control P. gingivali but were not as effective as a new drug that blocks the effects of the gingipain toxin. While much of the research was done on mice, the new drug is now being given to humans in a limited, controlled study. Preliminary results show the drug is safe and is already starting to improve AD. If all goes well a vaccine may eventually become available.

A key finding was that the presence of P. gingivali was not the result of AD, but rather could be the cause.

*Porphyromonas gingivalis in Alzheimer’s disease brains: Evidencefor disease causation and treatment with small molecule inhibitors. Stephen S.Dominy et. al. Science Advances 23 Jan 2019: Vol. 5, no. 1, eaau3333 DOI:10.1126/sciadv.aau3333

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