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Dr. Roger Seheult of MedCram explains new research on Neu5Gc, a sialic acid molecule found in meat and dairy, and how it may contribute to severe COVID-19 symptoms, inflammation, and certain chronic diseases and cancers, in the video published on May 13, 2021, “New Research: Sialic Acids May Contribute to Inflammation & Disease“, below:
Roger Seheult, MD is the co-founder and lead professor at MedCram https://www.medcram.com He is Board Certified in Internal Medicine, Pulmonary Disease, Critical Care, and Sleep Medicine and an Associate Professor at the University of California, Riverside School of Medicine.Bashir & Fezeu, et al. “Association between Neu5Gc carbohydrate and serum antibodies against it provides the molecular link to cancer: French NutriNet-Santé study.” BMC Medicine (2020) doi: 10.1186/s12916-020-01721-8 Read the article: http://dx.doi.org/10.1186/s12916-020-… In the video published on January 6, 2021, “Association between Neu5Gc carbohydrate and serum antibodies against it provides the molecular link“, below:
In the video published on Dec 13, 2012, “The InflammatoryMeat Molecule Neu5Gc“, below:
In the video published on Mar 30, 2019, “Meat, Neu5Gc and Inflammation – Does Eating Meat Increase Inflammation Because of Neu5Gc“, below:
In the video published on March 17, 2020, “Red Meat & Neu5Gc Protein – Nutrition Medicine Update # 138“, below:
For more about Neu5Gc (N-Glycolylneuraminic acid), please refer to the excerpt from wikipedia, in italics, below:N-Glycolylneuraminic acid (Neu5Gc) is a sialic acidmolecule found in most non-human mammals. Humans cannot synthesize Neu5Gc because the human gene CMAH is irreversibly mutated, though it is found in other apes. It is absent in human tissues because of inactivation of gene encoding CMP-N-acetylneuraminic acid hydroxylase. The gene CMAHencodes for CMP-N-acetylneuraminic acid hydroxylase, which is the enzyme responsible for CMP-Neu5Gc from CMP-N-acetylneuraminic (CMP-Neu5Ac) acid.This loss of CMAH is estimated to have occurred 2-3 million years ago, just before the emergence of the genus Homo.Neu5Gc is closely related to the commonly known N-acetylneuraminic acid (Neu5Ac). Neu5Acdiffers by a single oxygen atom that is added by the CMAH enzyme in the cytosolof a cell. In many mammals, both of these molecules are transferred into the Golgi so that they may be added to many glycoconjugates. However, in humans, Neu5Gc is not present.
Elimination of the Neu5Gc gene in humans
With the loss of Neu5Gc gene and gain of excess Neu5Ac, it should have affected the interactions of pathogens and humans. Humans should have been less susceptible to Neu5Gc-binding pathogens and more susceptible to Neu5Ac-binding pathogens. It is suggested that human ancestors lacking Neu5Gc production survived a then-prevailingmalaria epidemic. However, with the rise of Plasmodium falciparum, the parasite that causes malaria today, humans were once again endangered as this new strain of the malaria had a binding preference to the Neu5Ac-rich erythrocytes in humans.The latest research shows that humans who lack Neu5Ac on their red blood cells are less likely to get malaria from the parasites that cause it.
Neu5Gc is found in most mammals, with exceptions like humans, ferrets, the platypus, western dog breeds and New World monkeys.Trace amounts can be found in humans, even though the gene to encode for production of Neu5Gc was eliminated long ago. These trace amounts come from consumption of animals in human diet. Mainly, the sources are red meats such as lamb, pork, and beef. It can also be found in dairy products, but to a lesser extent. Some 1.1% of the identified Neu5Ac is actually Neu5Gc in commercial whey protein. Neu5Gc cannot be found in poultry and is found in only trace amounts in fish. This confirms that Neu5Gc is mainly found in foods of mammalian origin.Lanolin in shampoo also contains Neu5Gc.In 2017, scientists succeeded in indirectly identifying the presence of Neu5GC from multiple ancient animal fossils dated to over a million years ago, the oldest of which was dated to around 4Mya.
Effects on humans
Even though Neu5Gc is not known to be produced by any mechanism in the human body (due to lack of genes), our bodies do interact with trillions of microorganisms that are capable of complex biological reactions. Neu5Gc is reported to be found in concentration in human cancers, as well as in fecal samples, suggesting that humans ingest Neu5Gc as part of their diets. Uptake is thought to be by macropinocytosis, and the sialic acid can be transferred to the cytosol by a sialintransporter. It is possible that the immune system then recognizes the molecule as foreign, and that the binding of anti-Neu5Gc antibodies may then cause chronic inflammation. This assumption has yet to be concretely proven, however. Further studies have shown that humans have Neu5Gc-specific antibodies, often at high levels. Feeding Neu5Gc knockout mice Neu5Gc-rich diets along with anti-Neu5Gc antibodies (attempting to mimic a human system) causes systemic inflammation in the mice, and they are five times as likely to develop hepatocarcinomas. However, a study released in September 2018 found no evidence that exposure to higher levels of anti-Neu5gc antibodies increased colon cancer risk. 
Dietary absorption and excretion
A baseline excretion of Neu5Gc exists, and it is incorporated into all body parts, some of which—mucins, hair, saliva, serum and blood, are commonly excreted. Neu5Gc is rapidly absorbed in the intestinal tract, some of which is converted toacylmannosamines by intestinal cells and bacteria, and reconverted back to Neu5Gc in the body. According to an absorption study, about 3–6% of the ingested dose of Neu5Gc was excreted within 4–6 hours, with the peak excretion rate at 2–3 h and a return to baseline levels within 24 h. In mucins, an increase was seen from day 1 to 4, with increased also found in hair after ingestion.This table and this table(S3) shows levels of Neu5Gc in common foods.
Mechanism of uptake
Sialic acids are negatively charged and hydrophilic, so they don’t readily cross the hydrophobic regions of cellular membranes. It is because of this that the uptake of Neu5Gc must occur through an endocytic pathway. More specifically, exogenous Neu5Gc molecules enter cells through clathrin-independent endocytic pathways with help from pinocytosis. After the Neu5Gc has entered the cell via pinocytosis, the molecule is released by lysosomal sialidase. The molecule is then transferred into the cytosol by the lysosomal sialic acid transporter. From here, Neu5Gc are available for activation and addition to glycoconjugates. Because Neu5Gc appears to be enhanced in naturally occurring tumors andfetal tumors, it is suggested that this uptake mechanism is enhanced by growth factors.
For more about Sialic acid, please refer to the excerpt from wikipedia, in italics, below:Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone.The term “sialic acid” (from the Greek for saliva, σίαλον – síalon) was first introduced by Swedish biochemist Gunnar Blixin 1952. The most common member of this group is N-acetylneuraminic acid (Neu5Ac or NANA) found in animals and some prokaryotes.Sialic acids are found widely distributed in animal tissues and related forms are found to a lesser extent in other organisms like in some micro-algae, bacteria and archaea. Sialic acids are commonly part of glycoproteins, glycolipids or gangliosides, where they decorate the end of sugar chains at the surface of cells or soluble proteins. However, sialic acids have been also observed in Drosophila embryos and other insects. Generally, plants seem not contain or display sialic acids.In humans the brain has the highest sialic acid content, where these acids play an important role in neural transmission and ganglioside structure in synaptogenesis. More than 50 kinds of sialic acid are known, all of which can be obtained from a molecule of neuraminic acid by substituting its amino group of one of its hydroxyl groups. In general, the amino group bears either an acetyl or a glycolyl group, but other modifications have been described. These modifications along with linkages have shown to be tissue specific and developmentally regulated expressions, so some of them are only found on certain types of glycoconjugates in specific cells. The hydroxyl substituents may vary considerably; acetyl, lactyl, methyl, sulfate, and phosphate groups have been found.Siallic acids are related to several different diseases observed in humans, below:
Salla disease is an extremely rare illness which is considered the mildest form of the free sialic acid accumulation disorders though its childhood form is considered an aggressive variant and people who suffer from it have mental retardation. It is an autosomic recessive disorder caused by a mutation of the chromosome 6. It mainly affects the nervous system and it is caused by a lysosomal storage irregularity which comes from a deficit of a specific sialic acid carrier located on the lysosomal membrane Currently, there is no cure for this disease and the treatment is supportive, focusing on the control of symptoms.
All influenza A virus strains need sialic acid to connect with cells. There are different forms of sialic acids which have different affinity with influenza A virus variety. This diversity is an important fact that determines which species can be infected.When a certain influenza A virus is recognized by a sialic acid receptor the cell tends to endocytose the virus so the cell becomes infected.
Sialic acids and other nonulosonic acids (NulOs) in prokaryotes
Sialic acids are highly abundant in vertebrate tissues where they are involved in many different biological processes. Originally discovered within the Deuterostome lineage of animals, sialic acids can be actually considered as a subset of a more ancient family of 9-carbon backbone monosaccharides called nonulosonic acids (NulOs), which more recently have been also found in Eubacteria and Archaea.Many pathogenic bacteria incorporate sialic acid into cell surface features like theirlipopolysaccharide or capsule polysaccharides, which helps them to evade the innate immune response of the host. A recent genome level study examined a large set of sequenced microbial genomes, which indicated that biosynthetic pathways to produce nonulosonic acids (NulOs) are far more widely distributed across the phylogenetic tree of life, than previously realized. This finding is moreover supported by recent lectin staining studies and a molecular level survey on prokaryotic nonulosonic acids, showing that also many non-pathogenic and purely environmental strains produce bacterial sialic acids (NulOs).
I am a mother/wife/daughter, math professor, solar advocate, world traveler, yogi, artist, photographer, sharer of knowledge/information, and resident of Windermere, FL. I've worked professionally in applied math, engineering, medical research, and as a university math professor in IL and FL for about 20 years. My husband and I loved Disney and moved down to Central Florida initially as snowbirds. But we've come to love the warmth and friendly people offered by this community and decided to move down to Windermere, FL full time in 2006. I am now spending time sharing information/ knowledge online, promoting understanding of math and solar energy (via http://www.sunisthefuture.net ), and developing Windermere Sun (http://www.WindermereSun.com) as an online publication, sharing and promoting Community ABC's (Activities-Businesses-Collaborations) for healthier/happier/more sustainable living. In the following posts, I'll be sharing with you some of the reasons why Windermere has attracted us to become full-time residents of Central Florida region. Please feel free to leave your comments via email at "Contact Us" in the topbar above or via [email protected]
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