Gratitude for the analysis of advances in the metabolic interactions of fats. The redox balance of the oxidation and reduction processes occurs when the set of these chemical reactions remains stable. This is what is observed in normal physiology.
If, on the other hand, the body becomes unbalanced, the production of ROS accelerates. These molecules accumulate inside cells, oxidize the substances contained inside them, such as lipids, proteins and DNA, and alter them.
Redox balance is essential for cellular homeostasis. Overproduction of ROS and/or depletion of enzymatic and non-enzymatic antioxidant systems can lead to oxidative stress (OS) and its consequences.
Excess reducing equivalents can regulate cell signaling pathways, modify transcriptional activity, induce alterations in the formation of disulfide bonds in proteins, reduce mitochondrial function, decrease cellular metabolism and contribute to the development of some diseases in which NF- κB, a redox agent involved transcription factor. Some of these diseases are protein aggregation cardiomyopathy, hypertrophic cardiomyopathy, muscular dystrophy, pulmonary hypertension, rheumatoid arthritis, Alzheimer's disease and metabolic syndrome, among others (Table 1 of the first link).
There are environmental factors that intervene in the appearance of redox imbalance, such as a sedentary lifestyle, obesity, inadequate diet, smoking and environmental pollution, which also induce it. Cellular repair and the antioxidant system work together to counteract the damage caused by ROS. The endogenous ones are generally enzymes, such as peroxidases and catalases. The data reviewed show that long-lasting deviations from this redox state generate oxidative or reductive stress, which is responsible for inflammation, allergic and autoimmune reactions, and also contributes to aging.
Treatment with stearoylethanolamide (SEA) is neuroprotective against LPS-induced neuroinflammation. SEA restricted the spread of peripheral inflammation to the brain and prevented the activation of resident microglia and trafficking of leukocytes to the brain parenchyma. SEA improved the amplitude of synaptic vesicle release, supported balanced signal-to-noise ratio in glutamate and GABAergic neurotransmission, and decreased excitotoxic risk associated with higher glutamate levels.
Physical exercises stimulate the secretion of irisin, which is revealed as a powerful protector of the aforementioned organs and tissues. Together with melatonin, it can promote redox homeostasis
Recent publications also show ROS as compounds essentially linked to positive effects in relation to the athlete's health. The anti-inflammatory effect associated with exercise, muscle biogenesis from mechanisms sensitive to redox status, an improvement in glycogen restitution, and even an increase in muscle contractility and strength, are some of the positive effects of the cellular signals exerted by the ROS.
Dr. Mercola: “Marshall and I are developing a lab test to assess redox status by analyzing three pairs of compounds: lactate and pyruvate, acetoacetate and beta-hydroxybutyrate, and oxidized and reduced glutathione. “glutathione, a crucial antioxidant that, when in its reduced form, helps eliminate harmful substances but can also indicate reductive stress in cancer cells. Thus, maintaining a balanced level of reduced glutathione is essential for health.”
Mitochondria are essential for providing energy to maintain cell viability. Oxidative phosphorylation involves the transfer of electrons from energy substrates to oxygen to produce adenosine triphosphate. Mitochondria also regulate cell proliferation, metastasis, and deterioration. The flow of electrons in the mitochondrial respiratory chain generates reactive oxygen species (ROS), which at high levels are harmful to cells. Glutathione (GSH) is an abundant cellular antioxidant that is synthesized primarily in the cytoplasm and delivered to the mitochondria. Mitochondrial oxidative stress and mGSH depletion are involved in many pathological conditions associated with mitochondrial abnormalities and dysfunctions, as well as diseases and aging. Restoring mGSH levels and the GSH/GSSG ratio, as well as reducing ROS accumulation, are critical to maintaining mitochondrial function and antioxidant defense.
A long-term imbalance in the ratio of mitochondrial ROS and mGSH can cause cellular dysfunction, apoptosis, necroptosis, and ferroptosis, which can lead to disease. This study reviews the physiological functions, anabolism, variations in organ tissue accumulation and delivery of GSH to mitochondria and the relationships between mGSH levels, the GSH/GSH disulfide ratio (GSSG), programmed cell death and ferroptosis.
Dietary supplements are associated with increased levels of GSH and antioxidant effects, as well as levels of inflammation biomarkers. Probiotics can increase GSH levels, thereby reducing levels of inflammation and oxidative stress Table 2). Ginsenosides affect indicators related to oxidative stress, such as SOD, MDA, GSH, GSH-P X and catalase, and reduce the levels of inflammatory factors. A systematic review and meta-analysis showed that saffron supplementation can significantly increase TAC and GSH-P X levels, suggesting that saffron can reduce oxidative stress markers. The main mechanism of the neuroprotective effect of moringa extract and its phytochemical derivatives is to reduce oxidative stress by increasing the levels of antioxidant enzymes, reducing TAC levels and inducing the overproduction of SOD and GSH. Furthermore, a systematic review and meta-analysis showed that chromium supplementation significantly increases GSH levels. The anti-inflammatory and antioxidant properties of zinc may also have broad therapeutic effects in cardiovascular diseases. Zinc supplementation significantly reduced the levels of nitric oxide, MDA, TAC and GSH (Table 3). Also the second link presents a review exploring the connection between ferroptosis, the NRF2 pathway and atherosclerosis, emphasizing its role in protecting cells from oxidative stress and maintaining iron balance. The use of iron chelating agents to control iron overload conditions is discussed, with associated benefits and challenges. Finally, it highlights the importance of exploring therapeutic strategies that improve the glutathione (GSH) system and the potential of natural compounds such as quercetin, terpenoids and phenolic acids to reduce oxidative stress.
Above all, consider a diet that avoids the promotion of endotoxins related to metabolic diseases, including cardiovascular, neurodegenerative diseases and cancer. Excessive intake of fructose and linoleic acid in the normal human diet is related to a global increase in metabolic disorders. Chronic endotoxemia commonly occurs in obesity and is an important factor inducing systemic inflammation leading to metabolic syndrome. Healthy dietary choices, such as consumption of fish, fresh vegetables, and fruits and berries, may be associated with positive health outcomes. by reducing systemic endotoxemia. Vitamin D restriction and/or a high-fat diet increases the risk of metabolic endotoxemia. Phytochemicals reduce endotoxins.
Specific components of the Western diet, such as PUFAS, monosaccharides, processed fats, gluten, alcohol and additives, can affect the tight junctions between enterocytes, leading to increased permeability and the movement of endotoxins into the bloodstream. blood. These endotoxins include lipopolysaccharides derived from gram-negative bacteria.
In particular, a high-fructose diet can increase intestinal permeability and circulatory endotoxins by changing intestinal barrier function and microbial composition. Excess fructose causes inflammation and de novo lipogenesis. Lipogenesis leads to hepatic steatosis, thus causing abdominal adiposity and insulin resistance.
Serum endotoxin levels are elevated in patients with liver cirrhosis, diabetes, cardiovascular diseases, chronic infections and aging, amyotrophic lateral sclerosis, and Alzheimer's disease. The highest levels of plasma endotoxin are found in patients with sepsis, around 500 pg/ml.
Akkermansia muciniphila is a gram-negative and anaerobic bacteria, a microorganism considered one of the "new generation probiotics". Akkermansia muciniphila has antidiabetic, anti-inflammatory and anti-obesity effects, among others. When A. muciniphila colonizes the intestine, its metabolites interact with the intestinal barrier, affecting host health by strengthening the intestinal barrier, regulating the metabolic functions of the intestinal and circulatory systems, and regulating immune functions. This action is the most prominent since in these diseases its relationship is inversely proportional to the concentration of this bacteria.
It has even been shown that this bacteria is found in higher concentrations in older people, while its concentration is reduced in people with inflammation or chronic diseases.
Thus, a lower abundance of Akkermansia has been found in individuals with inflammatory bowel disease, ulcerative colitis or Crohn's disease, showing a clear relationship with intestinal immunity. In patients with acute appendicitis, its severity was inversely correlated with the amount of Akkermansia present. Likewise, it has been observed that the abundance of said bacteria is lower in individuals with psoriasis.
In addition to being related to beneficial effects on intestinal inflammation, the presence of Akkermansia muciniphila can mediate levels of hyperlipidemia and obesity. It has been observed that, in people with high weight and body mass index with high levels of cholesterol and blood glucose (fasting), the abundance of Akkermansia in the intestine is lower than that found in the intestine of people with weight and levels of normal cholesterol and glucose with link to weight loss and its multiple health benefits in obesity and type 2 diabetes.
In a meta-analysis it was reported that inulins, galactooligosaccharides (GOS) and polyphenols stimulate the growth of A. muciniphila) in the intestine. Furthermore, co-occurring microbial communities of A. muciniphila, such as Eubacterium hallii and Bacteroides, exhibited enhanced correlation with A. muciniphila
In a clinical study, it was observed that colonization of the intestine by the probiotic mixture based on Bifidobacterium longum and Lactobacillus rhamnosus increased the presence of Akkermansia muciniphila in the intestinal microbiota. Furthermore, Akkermansia muciniphila is also found in breast milk, transferring to the breastfed infant, which explains its appearance in the infant's intestine during the first stages of life.
The intake of prebiotics (substances resistant to digestion and fermentable by colonic bacteria) such as inulin stimulate the growth of said bacteria. Similarly, foods rich in polyphenols such as pomegranate, blueberry or procyanidins from apples or grapes and the intake of unsaturated fatty acids play an important role in the abundance and maintenance of normal levels of Akkermansia muciniphila in the intestinal microbiota. .
First, I just want to say, I'm always intrigued by your work- so thank you. (I work in the digestive health arena), but a couple of statements in this article threw me a bit. The following statement seems misleading, particularly given your other articles that discuss the benefits of gram positive bacteria such as Lactobacillus and Bifidobacteria. The statement in question - "Most beneficial bacteria are gram-negative, and they're called obligate anaerobes. They do not have LPS in their cell wall and hence will not produce endotoxin when they die off. "
My education and understanding is there are beneficial bacteria in both categories- gram negative and gram positive, just as there are detrimental in both categories, with lots of caveats. Regarding the LPS statement, perhaps I am reading it wrong, but it just seems incorrect. You state that gram negative bacteria do not have LPS in their cell wall and hence won't produce endotoxin, where in fact, LPS in the outer cell membrane is a fundamental characteristic of nearly all gram negative bacteria. Maybe because you are talking about Akkermansia muciniphila, which is gram negative and has been associated with more beneficial protective effects. Although Akkermansia m. is not associated with endotoxins, doesn't rule out the other gram negative bacteria that are. Or, maybe it's a typo??
Gratitude for the analysis of advances in the metabolic interactions of fats. The redox balance of the oxidation and reduction processes occurs when the set of these chemical reactions remains stable. This is what is observed in normal physiology.
If, on the other hand, the body becomes unbalanced, the production of ROS accelerates. These molecules accumulate inside cells, oxidize the substances contained inside them, such as lipids, proteins and DNA, and alter them.
Redox balance is essential for cellular homeostasis. Overproduction of ROS and/or depletion of enzymatic and non-enzymatic antioxidant systems can lead to oxidative stress (OS) and its consequences.
Excess reducing equivalents can regulate cell signaling pathways, modify transcriptional activity, induce alterations in the formation of disulfide bonds in proteins, reduce mitochondrial function, decrease cellular metabolism and contribute to the development of some diseases in which NF- κB, a redox agent involved transcription factor. Some of these diseases are protein aggregation cardiomyopathy, hypertrophic cardiomyopathy, muscular dystrophy, pulmonary hypertension, rheumatoid arthritis, Alzheimer's disease and metabolic syndrome, among others (Table 1 of the first link).
There are environmental factors that intervene in the appearance of redox imbalance, such as a sedentary lifestyle, obesity, inadequate diet, smoking and environmental pollution, which also induce it. Cellular repair and the antioxidant system work together to counteract the damage caused by ROS. The endogenous ones are generally enzymes, such as peroxidases and catalases. The data reviewed show that long-lasting deviations from this redox state generate oxidative or reductive stress, which is responsible for inflammation, allergic and autoimmune reactions, and also contributes to aging.
Treatment with stearoylethanolamide (SEA) is neuroprotective against LPS-induced neuroinflammation. SEA restricted the spread of peripheral inflammation to the brain and prevented the activation of resident microglia and trafficking of leukocytes to the brain parenchyma. SEA improved the amplitude of synaptic vesicle release, supported balanced signal-to-noise ratio in glutamate and GABAergic neurotransmission, and decreased excitotoxic risk associated with higher glutamate levels.
Physical exercises stimulate the secretion of irisin, which is revealed as a powerful protector of the aforementioned organs and tissues. Together with melatonin, it can promote redox homeostasis
Recent publications also show ROS as compounds essentially linked to positive effects in relation to the athlete's health. The anti-inflammatory effect associated with exercise, muscle biogenesis from mechanisms sensitive to redox status, an improvement in glycogen restitution, and even an increase in muscle contractility and strength, are some of the positive effects of the cellular signals exerted by the ROS.
https://www.mdpi.com/2076-3921/12/5/1126 (2023).--
https://www.sciencedirect.com/science/article/pii/S1568163723001150 (2023).--
https://www.sciencedirect.com/science/article/abs/pii/S2212429223000111 (2023).--
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00012-8 (2023).—
https://link.springer.com/article/10.1007/s00204-023-03562-9 (2023).--
https://www.liebertpub.com/doi/full/10.1089/ars.2019.7803 (2020).--
https://pubmed.ncbi.nlm.nih.gov/31881191/ (2020).--
https://www.sciencedirect.com/science/article/abs/pii/S0065230X21000336 (2021).--
https://www.tandfonline.com/doi/full/10.1080/19396368.2022.2119181 (2022).--
Dr. Mercola: “Marshall and I are developing a lab test to assess redox status by analyzing three pairs of compounds: lactate and pyruvate, acetoacetate and beta-hydroxybutyrate, and oxidized and reduced glutathione. “glutathione, a crucial antioxidant that, when in its reduced form, helps eliminate harmful substances but can also indicate reductive stress in cancer cells. Thus, maintaining a balanced level of reduced glutathione is essential for health.”
Mitochondria are essential for providing energy to maintain cell viability. Oxidative phosphorylation involves the transfer of electrons from energy substrates to oxygen to produce adenosine triphosphate. Mitochondria also regulate cell proliferation, metastasis, and deterioration. The flow of electrons in the mitochondrial respiratory chain generates reactive oxygen species (ROS), which at high levels are harmful to cells. Glutathione (GSH) is an abundant cellular antioxidant that is synthesized primarily in the cytoplasm and delivered to the mitochondria. Mitochondrial oxidative stress and mGSH depletion are involved in many pathological conditions associated with mitochondrial abnormalities and dysfunctions, as well as diseases and aging. Restoring mGSH levels and the GSH/GSSG ratio, as well as reducing ROS accumulation, are critical to maintaining mitochondrial function and antioxidant defense.
A long-term imbalance in the ratio of mitochondrial ROS and mGSH can cause cellular dysfunction, apoptosis, necroptosis, and ferroptosis, which can lead to disease. This study reviews the physiological functions, anabolism, variations in organ tissue accumulation and delivery of GSH to mitochondria and the relationships between mGSH levels, the GSH/GSH disulfide ratio (GSSG), programmed cell death and ferroptosis.
Dietary supplements are associated with increased levels of GSH and antioxidant effects, as well as levels of inflammation biomarkers. Probiotics can increase GSH levels, thereby reducing levels of inflammation and oxidative stress Table 2). Ginsenosides affect indicators related to oxidative stress, such as SOD, MDA, GSH, GSH-P X and catalase, and reduce the levels of inflammatory factors. A systematic review and meta-analysis showed that saffron supplementation can significantly increase TAC and GSH-P X levels, suggesting that saffron can reduce oxidative stress markers. The main mechanism of the neuroprotective effect of moringa extract and its phytochemical derivatives is to reduce oxidative stress by increasing the levels of antioxidant enzymes, reducing TAC levels and inducing the overproduction of SOD and GSH. Furthermore, a systematic review and meta-analysis showed that chromium supplementation significantly increases GSH levels. The anti-inflammatory and antioxidant properties of zinc may also have broad therapeutic effects in cardiovascular diseases. Zinc supplementation significantly reduced the levels of nitric oxide, MDA, TAC and GSH (Table 3). Also the second link presents a review exploring the connection between ferroptosis, the NRF2 pathway and atherosclerosis, emphasizing its role in protecting cells from oxidative stress and maintaining iron balance. The use of iron chelating agents to control iron overload conditions is discussed, with associated benefits and challenges. Finally, it highlights the importance of exploring therapeutic strategies that improve the glutathione (GSH) system and the potential of natural compounds such as quercetin, terpenoids and phenolic acids to reduce oxidative stress.
https://www.mdpi.com/1422-0067/25/2/1314 (2024).--
https://www.mdpi.com/2227-9059/12/3/558 (2024).--
Above all, consider a diet that avoids the promotion of endotoxins related to metabolic diseases, including cardiovascular, neurodegenerative diseases and cancer. Excessive intake of fructose and linoleic acid in the normal human diet is related to a global increase in metabolic disorders. Chronic endotoxemia commonly occurs in obesity and is an important factor inducing systemic inflammation leading to metabolic syndrome. Healthy dietary choices, such as consumption of fish, fresh vegetables, and fruits and berries, may be associated with positive health outcomes. by reducing systemic endotoxemia. Vitamin D restriction and/or a high-fat diet increases the risk of metabolic endotoxemia. Phytochemicals reduce endotoxins.
Specific components of the Western diet, such as PUFAS, monosaccharides, processed fats, gluten, alcohol and additives, can affect the tight junctions between enterocytes, leading to increased permeability and the movement of endotoxins into the bloodstream. blood. These endotoxins include lipopolysaccharides derived from gram-negative bacteria.
In particular, a high-fructose diet can increase intestinal permeability and circulatory endotoxins by changing intestinal barrier function and microbial composition. Excess fructose causes inflammation and de novo lipogenesis. Lipogenesis leads to hepatic steatosis, thus causing abdominal adiposity and insulin resistance.
Serum endotoxin levels are elevated in patients with liver cirrhosis, diabetes, cardiovascular diseases, chronic infections and aging, amyotrophic lateral sclerosis, and Alzheimer's disease. The highest levels of plasma endotoxin are found in patients with sepsis, around 500 pg/ml.
https://www.mdpi.com/2076-2607/11/2/267 (2023).--
https://www.sciencedirect.com/science/article/pii/S002231662304525X (2023).-
https://www.mdpi.com/2304-8158/12/19/3706 (2023).-
https://www.cghjournal.org/article/S1542-3565(22)01110-7/fulltext (2023).-
https://www.mdpi.com/2076-2607/11/2/267 (2023).-
https://www.sciencedirect.com/science/article/pii/S002231662304525X (2023)
https://www.mdpi.com/2304-8158/12/19/3706 (2023).-
https://www.sciencedirect.com/science/article/pii/S2405844023061042 (2023).-
https://link.springer.com/article/10.1007/s11739-023-03374-w (2024).--
https://onlinelibrary.wiley.com/doi/full/10.1111/eci.14224 (2024).---
https://www.cell.com/trends/endocrinology-metabolism/abstract/S1043-2760(24)00087-0 (2024).—
https://ejhm.journals.ekb.eg/article_349082.html (2024).--
Akkermansia muciniphila is a gram-negative and anaerobic bacteria, a microorganism considered one of the "new generation probiotics". Akkermansia muciniphila has antidiabetic, anti-inflammatory and anti-obesity effects, among others. When A. muciniphila colonizes the intestine, its metabolites interact with the intestinal barrier, affecting host health by strengthening the intestinal barrier, regulating the metabolic functions of the intestinal and circulatory systems, and regulating immune functions. This action is the most prominent since in these diseases its relationship is inversely proportional to the concentration of this bacteria.
It has even been shown that this bacteria is found in higher concentrations in older people, while its concentration is reduced in people with inflammation or chronic diseases.
Thus, a lower abundance of Akkermansia has been found in individuals with inflammatory bowel disease, ulcerative colitis or Crohn's disease, showing a clear relationship with intestinal immunity. In patients with acute appendicitis, its severity was inversely correlated with the amount of Akkermansia present. Likewise, it has been observed that the abundance of said bacteria is lower in individuals with psoriasis.
In addition to being related to beneficial effects on intestinal inflammation, the presence of Akkermansia muciniphila can mediate levels of hyperlipidemia and obesity. It has been observed that, in people with high weight and body mass index with high levels of cholesterol and blood glucose (fasting), the abundance of Akkermansia in the intestine is lower than that found in the intestine of people with weight and levels of normal cholesterol and glucose with link to weight loss and its multiple health benefits in obesity and type 2 diabetes.
In a meta-analysis it was reported that inulins, galactooligosaccharides (GOS) and polyphenols stimulate the growth of A. muciniphila) in the intestine. Furthermore, co-occurring microbial communities of A. muciniphila, such as Eubacterium hallii and Bacteroides, exhibited enhanced correlation with A. muciniphila
In a clinical study, it was observed that colonization of the intestine by the probiotic mixture based on Bifidobacterium longum and Lactobacillus rhamnosus increased the presence of Akkermansia muciniphila in the intestinal microbiota. Furthermore, Akkermansia muciniphila is also found in breast milk, transferring to the breastfed infant, which explains its appearance in the infant's intestine during the first stages of life.
The intake of prebiotics (substances resistant to digestion and fermentable by colonic bacteria) such as inulin stimulate the growth of said bacteria. Similarly, foods rich in polyphenols such as pomegranate, blueberry or procyanidins from apples or grapes and the intake of unsaturated fatty acids play an important role in the abundance and maintenance of normal levels of Akkermansia muciniphila in the intestinal microbiota. .
https://www.gutmicrobiotaforhealth.com/es/akkermansia-muciniphila-la-bacteria-que-podria-ayudar-a-combatir-el-sindrome-metabolico/ (2021).—
https://www.39ytu.com/ucam-capsa/akkermansia-muciniphila-la-bacteria-aliada-de-tu-organismo (2021).---
https://www.fundacionrenequinton.org/blog/akkermansia-muciniphila-bacteria-saludable/ (2021).--
https://www.tandfonline.com/doi/abs/10.1080/1040841X.2022.2037506 (2023).--
https://www.nature.com/articles/s41467-024-47275-8 (2024).--
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1370658/full (2024).--
https://www.frontiersin.org/articles/10.3389/frmbi.2024.1276015/full (2024).--
https://pubs.rsc.org/en/content/articlelanding/2024/fo/d4fo00428k/unauth (2024).--
https://www.preprints.org/manuscript/202403.1697/v1 (2024).--
First, I just want to say, I'm always intrigued by your work- so thank you. (I work in the digestive health arena), but a couple of statements in this article threw me a bit. The following statement seems misleading, particularly given your other articles that discuss the benefits of gram positive bacteria such as Lactobacillus and Bifidobacteria. The statement in question - "Most beneficial bacteria are gram-negative, and they're called obligate anaerobes. They do not have LPS in their cell wall and hence will not produce endotoxin when they die off. "
My education and understanding is there are beneficial bacteria in both categories- gram negative and gram positive, just as there are detrimental in both categories, with lots of caveats. Regarding the LPS statement, perhaps I am reading it wrong, but it just seems incorrect. You state that gram negative bacteria do not have LPS in their cell wall and hence won't produce endotoxin, where in fact, LPS in the outer cell membrane is a fundamental characteristic of nearly all gram negative bacteria. Maybe because you are talking about Akkermansia muciniphila, which is gram negative and has been associated with more beneficial protective effects. Although Akkermansia m. is not associated with endotoxins, doesn't rule out the other gram negative bacteria that are. Or, maybe it's a typo??