In Half I of this collection, I reviewed the biology of Neu5gc (“Neu5gc, Red Meat, and Human Disease: Part I,” January 14, 2015). Now it’s time for Half II: a take a look at whether or not mammalian meats (beef, lamb, pork, dairy) might assist provoke Hashimoto’s hypothyroidism.
Background on Autoimmunity
In case you solely care about well being and what to eat, skip to the subsequent part; however for many who need to perceive mechanisms, right here is the important thing background:
- Neu5gc is plentiful in almost all mammals, however is absent in people, ferrets, and new world monkeys.
- Neu5gc is a sialic acid. It supplies the terminal finish of the carbohydrates which coat cells and glycoproteins. Cells must be coated in these acids, as a result of in water acids turn into ions and give the cells a cost, which repels different cells. When sialic acids are sure by antibodies, the cost is misplaced, and cells clump or combination. In truth, clumping of cells after pig serum was injected into people was the primary signal that people type antibodies to pig cells. The primary antigens in pig cells are “alpha-gal” and Neu5gc.
- Though people can’t manufacture Neu5gc resulting from a mutation that occurred Three million years in the past, we retain the power to put it to use. So Neu5gc from meals can seem on the floor of human cells.
- To generate a broad-spectrum immune response, the DNA of B cells is re-organized to create novel mixtures of segments on the light- and heavy-chain parts of antibodies. This permits the physique to generate greater than 10^12 totally different antibodies.  To keep away from producing antibodies to human antigens, any B cells that generate antibodies whereas nonetheless in bone marrow are destroyed. However Neu5gc from meals doesn’t attain bone marrow, so there’s nothing to cease the formation of white blood cells able to producing antibodies to Neu5gc.
So Neu5gc has the potential to build up in human cells, particularly intestinal cells that are immediately uncovered to meals; and we will type antibodies to Neu5gc, which then might react to human cells which have included Neu5gc into their carbohydrate coat.
One may assume that this may be sufficient to generate autoimmunity, however extra is required. Though everybody has antibodies that may react to Neu5gc, the “preimmune repertoire” of antibodies binds to Neu5gc with very low affinity, and “low concentrations of anti-Neu5Gc antibodies do not seem to have any effect on Neu5Gc containing cells.”  In an effort to make excessive affinity antibodies, B cells have to be repeatedly stimulated by Neu5gc-containing antigens.
The most effective stimulation is offered by bacterial cell wall elements. As one paper states,
Micro organism are potent immunogens as a result of they categorical quite a few elements that may act as immune stimulants. Gram-damaging micro organism universally produce endotoxins which were proven to be highly effective immune system modulators by means of the Toll-like receptor Four (TLR4) on quite a lot of human immune cells. Lipoproteins on Gram-constructive and Gram-damaging cell surfaces can even work together with TLR2, leading to launch of cytokines concerned in B cell and T cell proliferation. As well as, bacterial DNA has been recognized for a few years to have the potential to stimulate the immune system. 
So to generate autoimmunity towards Neu5gc included in human cells, B cells should first be triggered to type excessive-affinity anti-Neu5gc antibodies by assembly bacterial pathogens who’ve included Neu5gc into their cell partitions.
This will occur as a result of some micro organism do incorporate sialic acids from their native surroundings into their cell partitions; and thus intestine micro organism will incorporate Neu5Gc from meals into cell partitions.
A main purpose for doing that is that, by coating themselves in sialic acids acquired from their host, they appear to be a “host cell” and are shielded from immune assault.  Many pathogens have discovered this trick:
Many pathogens secrete a sialidase that releases sialic acid from [nearby cells] … [O]ther sialic acid-using micro organism, such because the respiratory pathogen H. influenzae, lack genes for a sialidase …. Presumably free sialic acid is made obtainable to such pathogens by different, sialidase-expressing micro organism dwelling in the identical area of interest, or … by host sialidases which might be activated in the middle of irritation. 
Among the many pathogens recognized to make use of host sialic acids to defend themselves from human immunity is Neisseria gonorrhoeae, the pathogen that causes gonorrhea. It’s potential that gonorrhea an infection might result in autoimmunity by means of this mechanism.
Up to now, the revealed analysis on this matter has targeted on the potential of pathogens incorporating Neu5Ac, the first human sialic acid, from human cells into their cell partitions, and subsequently triggering autoimmunity towards Neu5Ac. There was little research of the likelihood that intestine pathogens will incorporate Neu5Gc from meals into their cell partitions, probably triggering autoimmunity towards Neu5Gc included in human cells.
But a current research  evaluating the degrees of Neu5Gc antibodies in human blood towards the prevalence of Hashimoto’s hypothyroidism means that this can be a big pathway for autoimmunity.
Hashimoto’s Hypothyroidism and Neu5Gc Antibody Ranges
That is one paper by which it’s virtually sufficient simply to current the info. Listed here are ranges of anti-Neu5Gc antibodies in sufferers with hypothyroidism vs wholesome controls:
That is Determine 1.  Sufferers with Hashimoto’s have, on common, 7-fold greater anti-Neu5Gc antibody ranges than the overall inhabitants. Sufferers with hypothyroidism, a few of whom have Hashimoto’s and some don’t, have an intermediate degree of anti-Neu5Gc antibodies.
Listed here are antibody ranges within the wholesome inhabitants (Determine 2a):
Few wholesome sufferers had greater than 16 mcg/mL of anti-Neu5Gc antibodies, and none had greater than 24 mcg/mL.
Listed here are antibody ranges in Hashimoto’s sufferers (Determine 2c):
Solely Three% of Hashi’s sufferers had lower than 12 mcg/mL of anti-Neu5Gc antibodies, and 57% had greater than 24 mcg/mL.
This can be a excellent separation of the 2 teams. It seems like when you can generate giant numbers of anti-Neu5Gc antibodies, then you’re virtually sure to get Hashimoto’s hypothyroidism.
About 50% (on this research, 47.9%) of hypothyroidism instances are autoimmune in origin. The 52.1% of hypothyroid sufferers who didn’t have Hashimoto’s usually had low ranges of anti-Neu5Gc antibodies, just like the wholesome controls. This remark strengthens the affiliation between anti-Neu5Gc antibodies and autoimmune hypothyroidism. It seems like anti-Neu5Gc antibodies are strongly linked to autoimmunity.
Including plausibility, “both autoantigens related to Hashimoto disease [thyroid peroxidase and/or thyroglobulin] are glycoproteins and N-linked carbohydrates containing sialic acids have been detected in both molecules.”  So it’s potential Neu5Gc is included instantly into thyroid peroxidase and thyroglobulin.
The research authors state, “this is the first study investigating the association of anti-Neu5Gc antibodies with autoimmune diseases such as hypothyroidism.” 
Additionally they examined for anti-Neu5Gc antibodies in rheumatoid arthritis sufferers, however discovered no connection there. Rheumatoid arthritis sufferers would not have elevated ranges of anti-Neu5Gc antibodies.
Their paper has not but been cited by some other papers. It seems to be just like the investigation of Neu5Gc-mediated autoimmunity is at its very beginnings.
Jim Beecham’s Expertise
Jim Beecham, MD, responded to my earlier publish with a private story:
I learn with curiosity your publish about Neu5Gc. I’m anxious to learn Half 2 which I perceive is coming. In the meantime I’ve been doing some research on the topic.
I suffered badly with childhood bronchial asthma, and I nonetheless get a type of asthmatic tightness of my respiration every so often. Prior to now few weeks have I noticed that is on days after I eat cheese and/or beef. This has ceased upon my chopping out purple meat and dairy this previous week.
I additionally get hypothyroid signs of chilly face and backs of arms now and again. I’m wondering if that is additionally linked to Neu5Gc …
In a second remark Jim added:
Right here’s one other thought re: Neu5Gc…which I can’t show however assume is probably going.
When an upsurge of titer of anti-Neu5Gc antibodies float in physique fluids, they’ve alternative trigger inflammatory response.
One researcher postulated this mechanism for hemolytic uremic syndrome.
My very own expertise is I develop a groin ‘heat rash’ sort response and irritable bladder a day or so after consuming an excessive amount of cheese and pink meat.
Jim’s private experiences add additional proof that Neu5Gc-driven irritation and autoimmunity is an actual phenomenon.
The paper linking Neu5Gc to hemolytic uremic syndrome is .
There’s a good chance that Hashimoto’s hypothyroidism is caused by a posh of things:
- An an infection within the intestine by bacterial pathogens that purchase Neu5Gc from meals (primarily beef and pork) and incorporate it into their cell partitions.
- A leaky intestine that (a) permits Neu5Gc from meals to enter the physique for subsequent incorporation into human cells, comparable to thyroid cells, and (b) creates both a systemic invasion of Neu5Gc-bearing intestine pathogens, or a “metabolic endotoxemia” during which Neu5Gc-bearing cell wall elements of intestine micro organism enter the physique, triggering formation of excessive-affinity anti-Neu5Gc antibodies.
- Vital consumption of beef and pork, offering the Neu5Gc to drive the autoimmune course of.
If so, then the technique for overcoming Hashi’s would contain:
- Enhancing intestine barrier integrity and mucosal immunity,
- Normalizing or diversifying the intestine flora, and
- Decreasing dietary Neu5Gc by changing beef, dairy, lamb, and pork with seafood and hen meats.
Neu5Gc-mediated autoimmunity doesn’t play a task in rheumatoid arthritis, however it might play a task in different autoimmune illnesses. The most certainly organ to be affected is the intestine, which is instantly uncovered to meals; endothelial cells, which line blood vessel partitions, and immune cells which flow into in blood, as blood is the subsequent location after the intestine uncovered to meals molecules getting into the physique; and lastly organs which work together intently with the blood, such because the thyroid. Hemolytic uremic syndrome is a situation of endothelial cell dysfunction.
So: it seems like discount of mammalian meats, changing them with seafood and fowl meats, could also be a prudent a part of a “Hashimoto’s protocol.” In autoimmune issues affecting the intestine, blood vessels, or immune cells, it might be value making an attempt a 30-day elimination of mammalian meats.
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References “Generation of Antibody Diversity,” in Alberts B, Johnson A, Lewis J, et al., Molecular Biology of the Cell, 4th version, New York: Garland Science; 2002, http://www.ncbi.nlm.nih.gov/books/NBK26860/.  Harvey HA, Swords WE, Apicella MA. The mimicry of human glycolipids and glycosphingolipids by the lipooligosaccharides of pathogenic neisseria and haemophilus. J Autoimmun. 2001 Might;16(Three):257-62. http://pmid.us/11334490.
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