It is very important that we take care of our health with healthy habits to avoid developing neurodegenerative diseases. Research shows that the gut microbiota of people with cognitive disorders differs from that of neurologically healthy older adults. Cognitive functions tend to decline with age, particularly memory. Episodic, working, and recognition memory are the most susceptible to age-related decline. One of the most common age-related cognitive impairments is dementia, and Alzheimer's disease (AD) is the most severe type of dementia.
Studies investigating the gut microbiota in individuals with AD have consistently reported a greater abundance of pro-inflammatory phyla and a decrease in anti-inflammatory phyla compared to age-matched control groups. A notable decrease in the Firmicutes phylum, an increase in the pro-inflammatory Bacteroidetes phylum, and a decrease in the Actinobacteria phylum were observed. This shift in these latter phyla was primarily driven by a significant reduction in the Bifidobacterium genus among participants with Alzheimer's disease (AD) in the United States, a genus known for its anti-inflammatory properties. Furthermore, a study of AD patients and participants with dementia elsewhere found that these individuals exhibited reduced diversity in their gut microbiota compared to normal aging control groups.
It has been reported that 10% of adults aged 70 and older were diagnosed with dementia in 2019. This gap is noteworthy, especially considering the incurable nature of Alzheimer's disease. There is a notable lack of emphasis on healthy aging in the context of gut microbiota and cognitive function.
Specific species of gut bacteria are associated with improved cognitive function. For example, the abundance of bacteria from the phylum Verrucomicrobia was found to be positively associated with verbal memory, visual scanning, working memory, and cognitive flexibility, while the phylum Firmicutes was associated with, among other things, improved immediate and delayed recall. Specific families within Firmicutes, such as Gemellaceae and Clostridiaceae, were associated with better concentration, memory speed, attention, and working memory quality. The Ruminococcus gauvreauii and Carnobacteriaceae groups within this phylum also showed positive correlations with certain cognitive functions, while Lachnospiraceae had an inverse association with cognition, such as spatial working memory. It appears that the Firmicutes/Bacteroidetes ratio (F/B, or Bacillota-to-Bacteroidota, according to more recent nomenclature) is another important factor in predicting cognitive function. The F/B ratio is often studied in the context of human health, particularly in relation to obesity and other metabolic conditions, but it also seems to be linked to cognitive health. In general, any deviation from the F/B ratio is considered dysbiosis and detrimental to the host. The F/B ratio is recognized as an important indicator of gut microbiota health and is also influenced by the amount of physical exercise, so it is not surprising that it may also influence the host's cognitive state.
We must consider that diets rich in fiber, polyphenols, and compounds with anti-inflammatory or antioxidant properties promote microbiome diversity and health. The components analyzed in a review, including berries, fermented papaya, hop flavonoids, and antioxidant vitamins, exhibit a combination of similar and diverse effects on cognitive function. Many of these interventions share common pathways, such as reducing oxidative stress, improving redox status, enhancing cerebral blood flow, strengthening gut-brain communication, supporting neuroprotection, and regulating mood through short-chain fatty acid (SCFA) production. Polyphenol-rich foods, such as berries, are particularly notable for their ability to improve memory, mood, and cognitive performance. These benefits are attributed to increased cerebral blood flow, improved endothelial function, and modulation of neuroprotective pathways. For example, the polyphenols present in blueberries and blackcurrants are linked to increased neurogenesis, while resveratrol and peanut-derived hydroxybenzoic acids reduce anxiety and improve memory thanks to their anti-inflammatory and antioxidant properties. Fermented papaya acts through various systemic pathways, improving oxidative balance and reducing damage to cellular components such as DNA and proteins. Although its effects are more systemic than localized to the brain, the reduction of oxidative stress indirectly promotes brain health by mitigating neuroinflammatory processes.
Antioxidant vitamins, such as vitamins C, B2, and D, improve cognitive function through various mechanisms. For example, vitamin C has been shown to reduce oxidative stress in brain tissue, promote neurotransmitter synthesis, and improve mental clarity. Vitamin D influences cognitive outcomes through its interaction with the vitamin D receptor (VDR), which regulates gene expression involved in brain function and neuroprotection. A combined treatment of vitamins C and B2 has demonstrated synergistic effects, further improving mood and memory in clinical trials. Vitamin supplementation yielded more consistent results, with higher levels of beneficial bacteria such as Akkermansia and Faecalibacterium, and increased SCFA production. Mechanistically, antioxidants support the production of SCFAs, such as butyrate, propionate, and acetate, which are key metabolites produced by the gut microbiota. SCFAs exert protective effects on the intestinal barrier by stimulating mucin production and the expression of tight junction proteins, such as occludin and claudin, thereby improving barrier integrity and reducing endotoxin translocation, which decreases systemic inflammation. In the context of the gut-brain axis, SCFAs modulate microglial activity in the brain, potentially reducing neuroinflammation and supporting neurogenesis in the hippocampus [9]. Antioxidants can also influence redox balance in the gut, promoting microbiome diversity and encouraging the growth of SCFA-producing bacteria, such as Faecalibacterium prausnitzii and Akkermansia muciniphila. In short, antioxidant supplementation, which includes vitamins C, B2, and D, as well as polyphenols like xanthohumol, fermented papaya, peanuts, and berry extracts, shows potential for improving cognitive function and gut health by modulating gut microbiome diversity and reducing inflammation. These antioxidants can support the gut-brain axis, primarily by increasing the production of short-chain fatty acids (SCFAs) and improving intestinal barrier integrity, which helps mitigate oxidative stress, a factor often associated with cognitive decline and neurodegenerative diseases.
Midwestern Doctor's research on DMSO is extraordinary. An interesting piece of news:
A NEW FINDING ABOUT A NATURAL COMPOUND OPENS THE DOOR TO INNOVATIVE THERAPIES FOR ALZHEIMER'S.
Scientists at the National University of Singapore have identified a metabolite present in the body as a potential tool to restore neuronal functions affected by the disease and delay cognitive decline.
According to a new study published in Aging Cell, calcium alpha-ketoglutarate (CaAKG), a metabolite naturally produced by the human body, has been identified as a potential tool to restore brain functions impaired by Alzheimer's.
This advance opens the door to potentially safer and more accessible therapeutic strategies to combat age-related cognitive decline.
A medicinal plant with ancestral uses in Brazil has shown effectiveness against arthritis in scientific research.
The study demonstrated that a natural metabolite can restore synaptic plasticity, key to memory and learning (Illustrative Image Infobae).
Brian K. Kennedy, from the Department of Biochemistry and chair of the Translational Research Program on Healthy Longevity (TRP), stated: “The research suggests that safe, natural compounds like CaAKG could one day complement existing approaches to protecting the brain and slowing memory loss.”
“Since AKG is already present in our bodies, focusing on these pathways could offer fewer risks and greater accessibility. This could provide us with a powerful new strategy to delay cognitive decline and promote healthy brain aging,” he noted.
The research team from the Yong Loo Lin School of Medicine at the National University of Singapore demonstrated that CaAKG can restore functionality to key neuronal processes altered in patients with Alzheimer's disease.
The compound, previously studied for its role in healthy aging, showed positive results in restoring synaptic plasticity, considered fundamental for learning and memory formation, a function severely impaired in this disease.
CaAKG allowed for the recovery of associative memory, one of the first abilities typically lost in the early stages of Alzheimer's, and restored synaptic retrieval, a mechanism that enables the brain to link events and form complex memories. Furthermore, it enhanced autophagy, the brain's natural system for eliminating harmful proteins, crucial for maintaining neuronal health.
The research indicates that CaAKG promotes the strengthening of connections between neurons by activating L-type calcium channels and calcium-permeable AMPA receptors, which are important for neuronal flexibility.
It also prevents the overload of NMDA receptors, frequently affected by the accumulation of amyloid protein, a hallmark of the disease. This multifaceted action suggests that CaAKG contributes both to maintaining basic memory function and to supporting more complex learning abilities.
Since AKG levels naturally decline with age, replenishing this metabolite could be a less risky and more accessible way to promote healthy brain aging.
Mercury exposure causes protein degradation, increased reactive oxygen species, and enzyme inhibition. It is suggested that neurodegenerative disorders occur due to defective protein degradation and aggregation, mitochondrial dysfunction related to oxidative stress and free radical formation, and the metal's toxicity. There is considerable evidence that mercury and its compounds cause neurodegenerative diseases. Toxic effects such as DNA fragmentation and impaired neuronal integrity can be observed due to mercury exposure. Severe neuronal damage results in neuronal loss, which in turn makes neurodegenerative diseases inevitable. In this review, we summarize studies on Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis, which are the main neurodegenerative diseases related to mercury exposure.
http://193.140.108.196:8080/handle/20.500.11851/11515 (2024).--- Aluminum is the most abundant neurotoxic metal in the Earth's crust. It accumulates semi-permanently in neuronal foci susceptible to Alzheimer's disease (AD) through the blood-brain barrier and the intracellular transferrin transport pathway, and is involved in the induction of oxidative stress, upregulation of the APP gene, and amyloid-β conformational changes. Some studies have reported increased morbidity or mortality from AD in areas with high Al exposure, suggesting that chronic Al exposure contributes to AD. Arsenic (As) is neurotoxic and impairs cognitive and memory functions. Exposure to As and its metabolites leads to the formation of reactive oxygen species (ROS), inflammation, mitochondrial dysfunction, and disruption not only of protein homeostasis but also of calcium signaling. Furthermore, As is a known cardiovascular toxin. The vascular hypothesis of Alzheimer's disease (AD) suggests that AD results from vascular damage that reduces cerebral blood perfusion rates and, therefore, indirectly damages neurons.
Magnesium (Mg) is the second most abundant intracellular divalent cation and a cofactor for more than 300 metabolic reactions in the body. It is neuroprotective, interacting with the N-methyl-D-aspartate (NMDA) receptor and blocking the calcium channel at the NMDA receptor, preventing oxidative stress and neuronal cell death due to excitotoxicity. Mg is also involved in normal neuronal maturation, neuromuscular transmission, and maintaining the integrity of the blood-brain barrier. Because the blood-brain barrier keeps daily fluctuations of blood Mg in check in brain tissue, cerebrospinal fluid appears to be a more representative biomaterial for analyzing Mg homeostasis in patients with AD. A systematic review of magnesium (Mg) levels in Alzheimer's disease (AD) patients found that Mg concentrations were significantly lower in the cerebrospinal fluid and hair of AD patients, but no differences were observed in serum and plasma. Lead (Pb) has complex and numerous mechanisms of neurotoxicity and is a known neurotoxin that causes nonspecific brain damage. Approximately 95% of the human lead burden is in bone. Bone lead has a half-life of 20 to 30 years, while the average turnover period for blood lead is approximately 30 days, and circulating lead levels are associated with acute exogenous exposures. Lead binds to divalent metal transporter proteins, crosses the blood-brain barrier in place of calcium (Ca), and accumulates in the brain. It causes oxidative stress by depleting thiols and impairing antioxidant defenses, leading to endoplasmic reticulum stress, mitochondrial damage, and neuronal apoptosis. In older populations, lead exposure is associated with lower cognitive status and longitudinal cognitive decline, but further prospective evidence from human clinical samples is needed.
Ginkgo biloba extract is widely used for its neuroprotective properties, which include improving cognitive function and memory, especially in age-related diseases such as Alzheimer's. Ascorbic acid is vital for collagen synthesis, tissue repair, and the enzymatic production of certain neurotransmitters. As a powerful antioxidant, ascorbic acid helps protect cells from damage caused by free radicals. The present study aimed to evaluate the effects of Ginkgo biloba and L-ascorbic acid on mercury-induced oxidative stress and neuroinflammation.
It is very important that we take care of our health with healthy habits to avoid developing neurodegenerative diseases. Research shows that the gut microbiota of people with cognitive disorders differs from that of neurologically healthy older adults. Cognitive functions tend to decline with age, particularly memory. Episodic, working, and recognition memory are the most susceptible to age-related decline. One of the most common age-related cognitive impairments is dementia, and Alzheimer's disease (AD) is the most severe type of dementia.
Studies investigating the gut microbiota in individuals with AD have consistently reported a greater abundance of pro-inflammatory phyla and a decrease in anti-inflammatory phyla compared to age-matched control groups. A notable decrease in the Firmicutes phylum, an increase in the pro-inflammatory Bacteroidetes phylum, and a decrease in the Actinobacteria phylum were observed. This shift in these latter phyla was primarily driven by a significant reduction in the Bifidobacterium genus among participants with Alzheimer's disease (AD) in the United States, a genus known for its anti-inflammatory properties. Furthermore, a study of AD patients and participants with dementia elsewhere found that these individuals exhibited reduced diversity in their gut microbiota compared to normal aging control groups.
It has been reported that 10% of adults aged 70 and older were diagnosed with dementia in 2019. This gap is noteworthy, especially considering the incurable nature of Alzheimer's disease. There is a notable lack of emphasis on healthy aging in the context of gut microbiota and cognitive function.
Specific species of gut bacteria are associated with improved cognitive function. For example, the abundance of bacteria from the phylum Verrucomicrobia was found to be positively associated with verbal memory, visual scanning, working memory, and cognitive flexibility, while the phylum Firmicutes was associated with, among other things, improved immediate and delayed recall. Specific families within Firmicutes, such as Gemellaceae and Clostridiaceae, were associated with better concentration, memory speed, attention, and working memory quality. The Ruminococcus gauvreauii and Carnobacteriaceae groups within this phylum also showed positive correlations with certain cognitive functions, while Lachnospiraceae had an inverse association with cognition, such as spatial working memory. It appears that the Firmicutes/Bacteroidetes ratio (F/B, or Bacillota-to-Bacteroidota, according to more recent nomenclature) is another important factor in predicting cognitive function. The F/B ratio is often studied in the context of human health, particularly in relation to obesity and other metabolic conditions, but it also seems to be linked to cognitive health. In general, any deviation from the F/B ratio is considered dysbiosis and detrimental to the host. The F/B ratio is recognized as an important indicator of gut microbiota health and is also influenced by the amount of physical exercise, so it is not surprising that it may also influence the host's cognitive state.
We must consider that diets rich in fiber, polyphenols, and compounds with anti-inflammatory or antioxidant properties promote microbiome diversity and health. The components analyzed in a review, including berries, fermented papaya, hop flavonoids, and antioxidant vitamins, exhibit a combination of similar and diverse effects on cognitive function. Many of these interventions share common pathways, such as reducing oxidative stress, improving redox status, enhancing cerebral blood flow, strengthening gut-brain communication, supporting neuroprotection, and regulating mood through short-chain fatty acid (SCFA) production. Polyphenol-rich foods, such as berries, are particularly notable for their ability to improve memory, mood, and cognitive performance. These benefits are attributed to increased cerebral blood flow, improved endothelial function, and modulation of neuroprotective pathways. For example, the polyphenols present in blueberries and blackcurrants are linked to increased neurogenesis, while resveratrol and peanut-derived hydroxybenzoic acids reduce anxiety and improve memory thanks to their anti-inflammatory and antioxidant properties. Fermented papaya acts through various systemic pathways, improving oxidative balance and reducing damage to cellular components such as DNA and proteins. Although its effects are more systemic than localized to the brain, the reduction of oxidative stress indirectly promotes brain health by mitigating neuroinflammatory processes.
Antioxidant vitamins, such as vitamins C, B2, and D, improve cognitive function through various mechanisms. For example, vitamin C has been shown to reduce oxidative stress in brain tissue, promote neurotransmitter synthesis, and improve mental clarity. Vitamin D influences cognitive outcomes through its interaction with the vitamin D receptor (VDR), which regulates gene expression involved in brain function and neuroprotection. A combined treatment of vitamins C and B2 has demonstrated synergistic effects, further improving mood and memory in clinical trials. Vitamin supplementation yielded more consistent results, with higher levels of beneficial bacteria such as Akkermansia and Faecalibacterium, and increased SCFA production. Mechanistically, antioxidants support the production of SCFAs, such as butyrate, propionate, and acetate, which are key metabolites produced by the gut microbiota. SCFAs exert protective effects on the intestinal barrier by stimulating mucin production and the expression of tight junction proteins, such as occludin and claudin, thereby improving barrier integrity and reducing endotoxin translocation, which decreases systemic inflammation. In the context of the gut-brain axis, SCFAs modulate microglial activity in the brain, potentially reducing neuroinflammation and supporting neurogenesis in the hippocampus [9]. Antioxidants can also influence redox balance in the gut, promoting microbiome diversity and encouraging the growth of SCFA-producing bacteria, such as Faecalibacterium prausnitzii and Akkermansia muciniphila. In short, antioxidant supplementation, which includes vitamins C, B2, and D, as well as polyphenols like xanthohumol, fermented papaya, peanuts, and berry extracts, shows potential for improving cognitive function and gut health by modulating gut microbiome diversity and reducing inflammation. These antioxidants can support the gut-brain axis, primarily by increasing the production of short-chain fatty acids (SCFAs) and improving intestinal barrier integrity, which helps mitigate oxidative stress, a factor often associated with cognitive decline and neurodegenerative diseases.
The links contain very interesting tables.
https://www.mdpi.com/2072-6643/16/6/852 (2024).--
https://pmc.ncbi.nlm.nih.gov/articles/PMC11764720/ (2025).--
Midwestern Doctor's research on DMSO is extraordinary. An interesting piece of news:
A NEW FINDING ABOUT A NATURAL COMPOUND OPENS THE DOOR TO INNOVATIVE THERAPIES FOR ALZHEIMER'S.
Scientists at the National University of Singapore have identified a metabolite present in the body as a potential tool to restore neuronal functions affected by the disease and delay cognitive decline.
According to a new study published in Aging Cell, calcium alpha-ketoglutarate (CaAKG), a metabolite naturally produced by the human body, has been identified as a potential tool to restore brain functions impaired by Alzheimer's.
This advance opens the door to potentially safer and more accessible therapeutic strategies to combat age-related cognitive decline.
A medicinal plant with ancestral uses in Brazil has shown effectiveness against arthritis in scientific research.
The study demonstrated that a natural metabolite can restore synaptic plasticity, key to memory and learning (Illustrative Image Infobae).
Brian K. Kennedy, from the Department of Biochemistry and chair of the Translational Research Program on Healthy Longevity (TRP), stated: “The research suggests that safe, natural compounds like CaAKG could one day complement existing approaches to protecting the brain and slowing memory loss.”
“Since AKG is already present in our bodies, focusing on these pathways could offer fewer risks and greater accessibility. This could provide us with a powerful new strategy to delay cognitive decline and promote healthy brain aging,” he noted.
The research team from the Yong Loo Lin School of Medicine at the National University of Singapore demonstrated that CaAKG can restore functionality to key neuronal processes altered in patients with Alzheimer's disease.
The compound, previously studied for its role in healthy aging, showed positive results in restoring synaptic plasticity, considered fundamental for learning and memory formation, a function severely impaired in this disease.
CaAKG allowed for the recovery of associative memory, one of the first abilities typically lost in the early stages of Alzheimer's, and restored synaptic retrieval, a mechanism that enables the brain to link events and form complex memories. Furthermore, it enhanced autophagy, the brain's natural system for eliminating harmful proteins, crucial for maintaining neuronal health.
The research indicates that CaAKG promotes the strengthening of connections between neurons by activating L-type calcium channels and calcium-permeable AMPA receptors, which are important for neuronal flexibility.
It also prevents the overload of NMDA receptors, frequently affected by the accumulation of amyloid protein, a hallmark of the disease. This multifaceted action suggests that CaAKG contributes both to maintaining basic memory function and to supporting more complex learning abilities.
Since AKG levels naturally decline with age, replenishing this metabolite could be a less risky and more accessible way to promote healthy brain aging.
https://www.infobae.com/salud/ciencia/2025/12/30/alzheimer-un-nuevo-hallazgo-sobre-un-compuesto-natural-abre-la-puerta-a-terapias-innovadoras/
Mercury exposure causes protein degradation, increased reactive oxygen species, and enzyme inhibition. It is suggested that neurodegenerative disorders occur due to defective protein degradation and aggregation, mitochondrial dysfunction related to oxidative stress and free radical formation, and the metal's toxicity. There is considerable evidence that mercury and its compounds cause neurodegenerative diseases. Toxic effects such as DNA fragmentation and impaired neuronal integrity can be observed due to mercury exposure. Severe neuronal damage results in neuronal loss, which in turn makes neurodegenerative diseases inevitable. In this review, we summarize studies on Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis, which are the main neurodegenerative diseases related to mercury exposure.
http://193.140.108.196:8080/handle/20.500.11851/11515 (2024).--- Aluminum is the most abundant neurotoxic metal in the Earth's crust. It accumulates semi-permanently in neuronal foci susceptible to Alzheimer's disease (AD) through the blood-brain barrier and the intracellular transferrin transport pathway, and is involved in the induction of oxidative stress, upregulation of the APP gene, and amyloid-β conformational changes. Some studies have reported increased morbidity or mortality from AD in areas with high Al exposure, suggesting that chronic Al exposure contributes to AD. Arsenic (As) is neurotoxic and impairs cognitive and memory functions. Exposure to As and its metabolites leads to the formation of reactive oxygen species (ROS), inflammation, mitochondrial dysfunction, and disruption not only of protein homeostasis but also of calcium signaling. Furthermore, As is a known cardiovascular toxin. The vascular hypothesis of Alzheimer's disease (AD) suggests that AD results from vascular damage that reduces cerebral blood perfusion rates and, therefore, indirectly damages neurons.
Magnesium (Mg) is the second most abundant intracellular divalent cation and a cofactor for more than 300 metabolic reactions in the body. It is neuroprotective, interacting with the N-methyl-D-aspartate (NMDA) receptor and blocking the calcium channel at the NMDA receptor, preventing oxidative stress and neuronal cell death due to excitotoxicity. Mg is also involved in normal neuronal maturation, neuromuscular transmission, and maintaining the integrity of the blood-brain barrier. Because the blood-brain barrier keeps daily fluctuations of blood Mg in check in brain tissue, cerebrospinal fluid appears to be a more representative biomaterial for analyzing Mg homeostasis in patients with AD. A systematic review of magnesium (Mg) levels in Alzheimer's disease (AD) patients found that Mg concentrations were significantly lower in the cerebrospinal fluid and hair of AD patients, but no differences were observed in serum and plasma. Lead (Pb) has complex and numerous mechanisms of neurotoxicity and is a known neurotoxin that causes nonspecific brain damage. Approximately 95% of the human lead burden is in bone. Bone lead has a half-life of 20 to 30 years, while the average turnover period for blood lead is approximately 30 days, and circulating lead levels are associated with acute exogenous exposures. Lead binds to divalent metal transporter proteins, crosses the blood-brain barrier in place of calcium (Ca), and accumulates in the brain. It causes oxidative stress by depleting thiols and impairing antioxidant defenses, leading to endoplasmic reticulum stress, mitochondrial damage, and neuronal apoptosis. In older populations, lead exposure is associated with lower cognitive status and longitudinal cognitive decline, but further prospective evidence from human clinical samples is needed.
https://link.springer.com/article/10.1186/s12302-024-00980-z (2024).--
Ginkgo biloba extract is widely used for its neuroprotective properties, which include improving cognitive function and memory, especially in age-related diseases such as Alzheimer's. Ascorbic acid is vital for collagen synthesis, tissue repair, and the enzymatic production of certain neurotransmitters. As a powerful antioxidant, ascorbic acid helps protect cells from damage caused by free radicals. The present study aimed to evaluate the effects of Ginkgo biloba and L-ascorbic acid on mercury-induced oxidative stress and neuroinflammation.
https://www.irrespub.com/biolsciences/index.php/1/article/view/197 (2024).
Can anyone tell me how to find dosing directions for intraveneous DMSO???