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Probiotics improve cognition in Alzheimer's
scma_2007
Posted: Wednesday, December 21, 2016 7:38 AM
Joined: 9/13/2013
Posts: 112


Science is proving that gut health and brain health are related. And that probiotics can help mood disorders and Alzheimer's.

Probiotics for Depression 2/21/2016

 https://www.psychologytoday.com/blog/evolutionary-psychiatry/201602/probiotics-depression

The Best Probiotics for Mood 11/11/2016

http://universityhealthnews.com/daily/depression/the-best-probiotics-for-mood-enhancing-the-gut-brain-connection-with-psychobiotics/

Probiotics Improve Cognition in Alzheimer's 11/10/2016

https://www.sciencedaily.com/releases/2016/11/161110162840.htm

And this could be the link -

Powerful defenders of the brain discovered, with big implications for disease and injury 

(Immune cells maybe the  mediator between the gut and the brain)

https://www.sciencedaily.com/releases/2016/12/161219120113.htm  12/19/2016


Lane Simonian
Posted: Wednesday, December 21, 2016 10:12 AM
Joined: 12/12/2011
Posts: 4396


This may be another link between at least some probiotics and the treatment of Alzheimer's disease.

Proteomic proof that a probiotic elevates glutathione level in human serum

Abstract: Lactobacillus fermentum ME-3 (LfME-3) has been proven to synthesize and secrete glutathione. A regular use of the foods fermented by it has shown a favourable influence on human lipid profiles and several antioxidant parameters...Glutathione (L-gamma-Glu-L-Cys-Gly or GSH) is a major cellular non-enzymatic antioxidant. It eliminates reactive oxygen species (ROS) such as lipid and hydrogen peroxides, hydroxyl radicals and peroxynitrite, mainly via cooperation with selenium-dependent glutathione peroxidase [14,15].

There is a very close correlation between the decline in glutathione levels and cognitive impairment:

The hippocampi – the brain centres for learning and memory – are one of the earliest regions to be sabotaged by Alzheimer’s pathology. Our data revealed that GSH [glutathione] levels plummet in the hippocampi of patients with Alzheimer’s as well as those with MCI (Fig.1). The frontal cortices – brain CEOs responsible for a variety of executive functions – are chronologically affected later in Alzheimer’s. GSH levels mimic this chronology with no changes in the cortices of MCI patients, but significant reduction in those of Alzheimer’s patients (Fig.1). Interestingly, GSH remains unaffected in the cerebellum – a brain region unaffected by Alzheimer’s till late stages. It appears GSH decline is not ubiquitous but rather a region-specific phenomenon that appears to precisely map the progression of Alzheimer’s in our brains.

So perhaps among other positive functions certain probiotics increase glutathione levels in the brain which provides some protection against oxidative stress in Alzheimer's disease.

 


onward
Posted: Wednesday, December 21, 2016 10:29 AM
Joined: 12/20/2011
Posts: 217


Scma, thanks very much for your post.

From an article you linked:

 

Probiotics improve cognition in Alzheimer's patients

Date: November 10, 2016

For the first time, scientists have shown that probiotics -- beneficial live bacteria and yeasts taken as dietary supplements -- can improve cognitive function in humans. In a new clinical trial, scientists show that a daily dose of probiotic Lactobacillus and Bifidobacterium bacteria taken over a period of just 12 weeks is enough to yield a moderate but significant improvement in the score of elderly Alzheimer's patients on the Mini-Mental State Examination (MMSE) scale, a standard measure of cognitive impairment.
 
 
... the patients daily received 200 ml [= about 6.7 US fluid ounces?] milk enriched with four probiotic bacteria

Lactobacillus acidophilus,
L. casei,
L. fermentum,
and Bifidobacterium bifidum
(approximately 400 billion bacteria per species),...
 
... Over the course of the study, the average score on the MMSE questionnaire significantly increased (from 8.7 to 10.6, out of a maximum of 30) in the group receiving probiotics, but not in the control group (from 8.5 to 8.0)...
 
 
 
 
 
 
Can anyone find a product with the same probiotics and dosage that this successful study used?
 
 

So far, the product I see at amazon.com that comes closest is:

Hyperbiotics PRO-15 Advanced Strength Probiotics (Hyperbiotics also offers a much less potent product, so don't confuse the two.)

I think it contains the 4 strains used in the study, but along with a bunch of other things not used in the study.

The dosage is 1 to 3 tablets per day, each of which, if I understand right, contains

"15 Billion Colony Forming Units per BIO-tract pearl" [I think they mean "tablet"] "- which is equivalent to 225 Billion CFU (colony forming units) of standard probiotic capsules." 

 

In the successful Alzheimer's study, each patient received a probiotic-fortified milk supplement daily with "approximately 400 billion bacteria per species."

 

Does anyone know how these doses compare?

 

I wonder if there's any brand of milk or yogurt etc. that contains what the successful study used. Can anyone here find anything? Thanks.


scma_2007
Posted: Tuesday, January 10, 2017 6:08 AM
Joined: 9/13/2013
Posts: 112


 
Lane, thanks for your interesting post on the glutathione and probiotic connection.
 
My mother is taking  Dr Ohhira"s original formula probiotic together with prebiotics twice a day. It is a proprietary blend of 900 million CFUs of 12 strains probiotics with prebiotics and biogenics. She takes them on empty stomach. The result is encouraging. Her spatial ability has improved just like in the clinical trials. She used to miss grabbing  a glass of water by 5 inches on the side. Now she grabs it spot on.

We got the brand as it is the best one we can find in our country.  We know it is nowhere near the clinical trial dosage.

Some experts say that probiotics are best on empty stomach as they won't survive stomach acid that is excreted during the digestion of food. Others say that it has to be taken with food as the probiotics need food to survive. We followed the empty stomach way but added prebiotics.

The clinical trial had the probiotics mixed in milk. This means it is with food. Maybe that's why very high CFUs is needed.

I am sharing this info from our experience. I am sure every Alzheimer's patient is different. The gut flora varies in every person. I would appreciate feedback from other people's experience with the use of probiotics. 

Note that my mother is also doing  most of what is in Bredesen Protocol. The protocol, it seems to me, is a compilation of many researches in the field of Alzheimer's. We are also using aromatherapy. In this fight against this cruel disease, we try and do anything that helps.


Lane Simonian
Posted: Saturday, January 21, 2017 12:45 PM
Joined: 12/12/2011
Posts: 4396



I stumbled across this article today about the relationship between declining levels of glutathione and various inflammatory intestinal diseases.

http://sanjosefuncmed.com/intestinal-permeability-clinical-unwinding-leaky-gut/

You dont get leakiness of gut until glutathione stores are depleted

And the same holds true for Alzheimer's disease.

Glutathione is a key antioxidant in the body and it is depleted by oxidants. Peroxynitrite is a strong antibacterial but it also kills bacteria that produce glutathione and it also depletes a compound (NAD+) needed for reduced glutathione. And when converted to nitrate (NO3-), peroxynitrite contributes to the spread of harmful bacteria.

Peroxynitrite is a combination of inducible nitric oxice and superoxide anions. Inhibiting inducible nitric oxide production inhibits both a leaky gut and a leaky brain and may help in treating both inflammatory intestinal diseases and Alzheimer's disease.

It is known that the overproduction of iNOS is related to intestinal destruction and inflammation. iNOS inhibitors should be considered as potential anti-inflammatory agents for intestinal injury.”

Brains from subjects who have Alzheimer's disease (AD) express inducible nitric oxide synthase (iNOS). We tested the hypothesis that iNOS contributes to AD pathogenesis. Immunoreactive iNOS was detected in brains of mice with AD-like disease resulting from transgenic expression of mutant human beta-amyloid precursor protein (hAPP) and presenilin-1 (hPS1). We bred hAPP-, hPS1-double transgenic mice to be iNOS(+/+) or iNOS(-/-), and compared them with a congenic WT strain. Deficiency of iNOS substantially protected the AD-like mice from premature mortality, cerebral plaque formation, increased beta-amyloid levels, protein tyrosine nitration, astrocytosis, and microgliosis. Thus, iNOS seems to be a major instigator of beta-amyloid deposition and disease progression. Inhibition of iNOS may be a therapeutic option in AD.

I have celiac disease most likely caused by pesticides on wheat, which puts me at greater risk for Non-hodgkin lymphoma and Alzheimer's disease (which took the life of Gene Wilder).  The following connections, thus, interest me.

 2014 Jan-Feb;33(1):29-38. doi: 10.1177/1091581813517906. Epub 2014 Jan 16.

Glyphosate commercial formulation causes cytotoxicity, oxidative effects, and apoptosis on human cells: differences with its active ingredient.

Abstract

In the present study, the effects on oxidative balance and cellular end points of glyphosate, aminomethylphosphonic acid (AMPA), and a glyphosate formulation (G formulation) [of the herbicide Roundup] were examined in HepG2 cell line, at dilution levels far below agricultural recommendations. Our results show that G formulation had toxic effects while no effects were found with acid glyphosate and AMPA treatments. Glyphosate formulation exposure produced an increase in reactive oxygen species, nitrotyrosine formation, superoxide dismutase activity, and glutathione (GSH) levels, while no effects were observed for catalase and GSH-S-transferase activities. Also, G formulation triggered caspase 3/7 activation and hence induced apoptosis pathway in this cell line. Aminomethylphosphonic acid exposure produced an increase in GSH levels while no differences were observed in other antioxidant parameters. No effects were observed when the cells were exposed to acid glyphosate. These results confirm that G formulations have adjuvants working together with the active ingredient and causing toxic effects that are not seen with acid glyphosate.


It is important to avoid gluten if you have intestinal permeability. Once intestinal permeability develops, gluten sensitivity will develop in almost all cases. Gluten sensitivity will also promote intestinal permeability by activating zonulin (the protein that binds the epithelial cells together). Gluten has been shown to activate the zonulin system directly and continue to promote leaky gut.


Maybe people have genes that increase zonulin just like there are people that have genes that increase amyloid production and that leads to Celiac disease and Alzheimer's disease, but the exposure to other toxins leads to a more rapid onset even in these genetic cases. And in later onset cases, the primary culprit may have only a little to do with zonulin and amyloid.


The "grain brain" may represent a dual threat--one it increases glucose levels in the brain and two it may expose the brain to high levels of toxic pesticides.


These are just some thoughts about the brain-gut connection.




Lane Simonian
Posted: Saturday, January 21, 2017 9:26 PM
Joined: 12/12/2011
Posts: 4396



This is somewhat generalized but interesting nevertheless.

The human gut microbiome impacts human brain health in numerous ways: (1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation. (2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system. (3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity. (4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence. (5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurologic manifestations of celiac disease is being studied. Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics.


Lane Simonian
Posted: Saturday, January 21, 2017 9:44 PM
Joined: 12/12/2011
Posts: 4396


This may be a case of putting A and B together to get C.

 2009 Mar;390(3):191-214. doi: 10.1515/BC.2009.033.

Glutathione dysregulation and the etiology and progression of human diseases.

Abstract

Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and as a result, disturbances in GSH homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases of aging, cystic fibrosis, and cardiovascular, inflammatory, immune, metabolic, and neurodegenerative diseases. Owing to the pleiotropic effects of GSH on cell functions, it has been quite difficult to define the role of GSH in the onset and/or the expression of human diseases, although significant progress is being made. GSH levels, turnover rates, and/or oxidation state can be compromised by inherited or acquired defects in the enzymes, transporters, signaling molecules, or transcription factors that are involved in its homeostasis, or from exposure to reactive chemicals or metabolic intermediates. GSH deficiency or a decrease in the GSH/glutathione disulfide ratio manifests itself largely through an increased susceptibility to oxidative stress, and the resulting damage is thought to be involved in diseases, such as cancer, Parkinson's disease, and Alzheimer's disease. In addition, imbalances in GSH levels affect immune system function, and are thought to play a role in the aging process. Just as low intracellular GSH levels decrease cellular antioxidant capacity, elevated GSH levels generally increase antioxidant capacity and resistance to oxidative stress, and this is observed in many cancer cells. The higher GSH levels in some tumor cells are also typically associated with higher levels of GSH-related enzymes and transporters. Although neither the mechanism nor the implications of these changes are well defined, the high GSH content makes cancer cells chemoresistant, which is a major factor that limits drug treatment. The present report highlights and integrates the growing connections between imbalances in GSH homeostasis and a multitude of human diseases.


Nitric Oxide and Peroxynitrite in Health and Disease


The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.


 2000 May;74(5):1989-98.

Synergistic depletion of astrocytic glutathione by glucose deprivation and peroxynitrite: correlation with mitochondrial dysfunction and subsequent cell death.

Abstract

Previously we reported that immunostimulated astrocytes were highly vulnerable to glucose deprivation. The augmented death was mimicked by the peroxynitrite (ONOO )-producing reagent 3-morpholinosydnonimine (SIN-1). Here we show that glucose deprivation and ONOO- synergistically deplete intracellular reduced glutathione (GSH) and augment the death of astrocytes via formation of cyclosporin A-sensitive mitochondrial permeability transition (MPT) pore. Astrocytic GSH levels were only slightly decreased by glucose deprivation or SIN-1 (200 microM) alone. In contrast, a rapid and large depletion of GSH was observed in glucose-deprived/ SIN-1-treated astrocytes. The depletion of GSH occurred before a significant release of lactate dehydrogenase (a marker of cell death). Superoxide dismutase and ONOO-scavengers completely blocked the augmented death, indicating that the reaction of nitric oxide with superoxide to form ONOO was implicated. Furthermore, nitrotyrosine immunoreactivity (a marker of ONOO-) was markedly enhanced in glucose-deprived/SIN-1 -treated astrocytes. Mitochondrial transmembrane potential (MTP) was synergistically decreased in glucose-deprived/SIN-1-treated astrocytes. The glutathione synthase inhibitor L-buthionine-(S,R)-sulfoximine markedly decreased the MTP and increased lactate dehydrogenase (LDH) releases in SIN-1-treated astrocytes. Cyclosporin A, an MPT pore blocker, completely prevented the MTP depolarization as well as the enhanced LDH releases in glucose-deprived/SIN-1-treated astrocytes.


Lane Simonian
Posted: Saturday, January 21, 2017 10:22 PM
Joined: 12/12/2011
Posts: 4396


And to connect this directly back to the topic at hand:  

Researchers recently discovered that Lactobacillus fermentum ME-3, another unique strain, produces a compound that possesses a striking array of powerful antioxidant, antimicrobial, anti-inflammatory, and detoxifying properties.

ME-3's probiotic power derives largely from its ability to produce glutathione, a critical disease-fighting compound. Often referred to as the "master antioxidant," glutathione is the mostly highly concentrated antioxidant in the body. It exists inside every single human cell and serves a wide range of important bodily functions.

L. fermentum ME-3 supports healthy glutathione levels in three key ways: synthesis, uptake, and regeneration. First, the bacterial strain is able to directly synthesize glutathione on its own. When the antioxidant isn’t present, ME-3 can also extract available glutathione molecules from the surrounding environment. Additionally, ME-3 recycles oxidized or "spent" glutathione back into its active state. Because it works along all three of these pathways, scientists consider ME-3 to be a "complete glutathione system."

Kullisaara et al. argue that ME-3’s capacity to generate glutathione makes it "a perfect protector against oxidative stress".

Complementing its antioxidant properties, glutathione supports immune health via its role in the creation of white blood cells. Additionally, glutathione production is associated with significant reductions in IL-6 and other proinflammatory cytokines.

Although glutathione is present in all human cells, the liver is the primary producer and exporter. Not surprisingly, the antioxidant also plays a critical role in the detoxification process. It protects hepatic cells from heavy metals including mercury, lead, cadmium, and other environmental toxins, and also reduces tissue susceptibility to toxicity from drugs like alcohol and acetaminophen.

Researchers have linked glutathione deficiency to a range of disorders, including liver disease, cystic fibrosis, sickle cell anemia, HIV, AIDS, cancer, heart attack, stroke, diabetes, kwashiorkor, seizures, and Alzheimer’s and Parkinson’s diseases. Notably, even in healthy individuals, the body naturally begins to produce less glutathione over time. After age 20, production declines at a rate of about 1% per year. 

Antioxidant-boosting probiotics may benefit those with low glutathione levels. Some have suggested that because it’s a peptide, oral glutathione supplements may be degraded by peptidase enzymes during digestion.  

Probiotics like L. fermentum ME-3 offer a potential workaround, instead prompting the body to produce essential nutrients from within.

Researcher heal thyself.


Serenoa
Posted: Monday, January 23, 2017 5:35 AM
Joined: 4/24/2012
Posts: 483


This is all good information. It reminds me that the elimination of our exposure to probiotics is a relatively recent development associated with the advance of Western civilization. In the past, probiotics were a regular part of the diet in the form of fermented foods. We used these microbes to make our foods like sourkraut, cheese, vine, etc. Nothing was pasturized, sterilized, frozen, even refrigerated. Bread, cheese and pies sat out on the table, milk was raw, eggs weren't put in the fridge, fruit and vegetables were not washed. We no doubt have a probiotic deficiency due to our Western dietary practices.
 
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