In Part I of this series, I reviewed the biology of Neu5gc (“Neu5gc, Red Meat, and Human Disease: Part I,” January 14, 2015). Now it’s time for Part II: a look at whether mammalian meats (beef, lamb, pork, dairy) may help provoke Hashimoto’s hypothyroidism.
Background on Autoimmunity
If you only care about health and what to eat, skip to the next section; but for those who want to understand mechanisms, here is the key background:
- Neu5gc is abundant in nearly all mammals, but is absent in humans, ferrets, and new world monkeys.
- Neu5gc is a sialic acid. It provides the terminal end of the carbohydrates which coat cells and glycoproteins. Cells need to be coated in these acids, because in water acids become ions and give the cells a charge, which repels other cells. When sialic acids are bound by antibodies, the charge is lost, and cells clump or aggregate. In fact, clumping of cells after pig serum was injected into humans was the first sign that humans form antibodies to pig cells. The main antigens in pig cells are “alpha-gal” and Neu5gc.
- Although humans cannot manufacture Neu5gc due to a mutation that occurred 3 million years ago, we retain the ability to utilize it. So Neu5gc from food can appear on the surface of human cells.
- To generate a broad-spectrum immune response, the DNA of B cells is re-arranged to create novel combinations of segments on the light- and heavy-chain portions of antibodies. This enables the body to generate more than 10^12 different antibodies. [1] To avoid generating antibodies to human antigens, any B cells that generate antibodies while still in bone marrow are destroyed. But Neu5gc from food doesn’t reach bone marrow, so there is nothing to stop the formation of white blood cells capable of generating antibodies to Neu5gc.
So Neu5gc has the potential to accumulate in human cells, especially intestinal cells which are directly exposed to food; and we can form antibodies to Neu5gc, which then may react to human cells which have incorporated Neu5gc into their carbohydrate coat.
One might think that this would be enough to generate autoimmunity, but more is needed. Although everyone has antibodies that can 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.” [4] In order to make high affinity antibodies, B cells must be repeatedly stimulated by Neu5gc-containing antigens.
The best stimulation is provided by bacterial cell wall components. As one paper states,
Bacteria are potent immunogens because they express a number of factors that can act as immune stimulants. Gram-negative bacteria universally produce endotoxins that have been shown to be powerful immune system modulators through the Toll-like receptor 4 (TLR4) on a variety of human immune cells. Lipoproteins on Gram-positive and Gram-negative cell surfaces can also interact with TLR2, resulting in release of cytokines involved in B cell and T cell proliferation. In addition, bacterial DNA has been known for many years to have the capability to stimulate the immune system. [2]
So to generate autoimmunity against Neu5gc incorporated in human cells, B cells must first be triggered to form high-affinity anti-Neu5gc antibodies by meeting bacterial pathogens who have incorporated Neu5gc into their cell walls.
This can happen because some bacteria do incorporate sialic acids from their local environment into their cell walls; and thus gut bacteria will incorporate Neu5Gc from food into cell walls.
A primary reason for doing this is that, by coating themselves in sialic acids acquired from their host, they look like a “host cell” and are shielded from immune attack. [5] Many pathogens have learned this trick:
Many pathogens secrete a sialidase that releases sialic acid from [nearby cells] … [O]ther sialic acid-utilizing bacteria, such as the respiratory pathogen H. influenzae, lack genes for a sialidase …. Presumably free sialic acid is made available to such pathogens by other, sialidase-expressing bacteria living in the same niche, or … by host sialidases that are activated in the course of inflammation. [3]
Among the pathogens known to use host sialic acids to shield themselves from human immunity is Neisseria gonorrhoeae, the pathogen that causes gonorrhea. It is possible that gonorrhea infection could lead to autoimmunity through this mechanism.
To date, the published research on this topic has focused on the possibility of pathogens incorporating Neu5Ac, the primary human sialic acid, from human cells into their cell walls, and subsequently triggering autoimmunity against Neu5Ac. There has been little study of the possibility that gut pathogens will incorporate Neu5Gc from food into their cell walls, potentially triggering autoimmunity against Neu5Gc incorporated in human cells.
Yet a recent study [4] comparing the levels of Neu5Gc antibodies in human blood against the prevalence of Hashimoto’s hypothyroidism suggests that this may be a significant pathway for autoimmunity.
Hashimoto’s Hypothyroidism and Neu5Gc Antibody Levels
This is one paper in which it’s almost enough just to present the data. Here are levels of anti-Neu5Gc antibodies in patients with hypothyroidism vs healthy controls:
This is Figure 1. [4] Patients with Hashimoto’s have, on average, 7-fold higher anti-Neu5Gc antibody levels than the general population. Patients with hypothyroidism, some of whom have Hashimoto’s and some don’t, have an intermediate level of anti-Neu5Gc antibodies.
Here are antibody levels in the healthy population (Figure 2a):
Few healthy patients had more than 16 mcg/mL of anti-Neu5Gc antibodies, and none had more than 24 mcg/mL.
Here are antibody levels in Hashimoto’s patients (Figure 2c):
Only 3% of Hashi’s patients had less than 12 mcg/mL of anti-Neu5Gc antibodies, and 57% had more than 24 mcg/mL.
This is a very good separation of the two groups. It looks like if you can generate large numbers of anti-Neu5Gc antibodies, then you are almost certain to get Hashimoto’s hypothyroidism.
About 50% (in this study, 47.9%) of hypothyroidism cases are autoimmune in origin. The 52.1% of hypothyroid patients who didn’t have Hashimoto’s generally had low levels of anti-Neu5Gc antibodies, similar to the healthy controls. This observation strengthens the association between anti-Neu5Gc antibodies and autoimmune hypothyroidism. It looks like anti-Neu5Gc antibodies are strongly linked to autoimmunity.
Adding 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.” [4] So it’s possible Neu5Gc is incorporated directly into thyroid peroxidase and thyroglobulin.
The study authors state, “this is the first study investigating the association of anti-Neu5Gc antibodies with autoimmune diseases such as hypothyroidism.” [4]
They also tested for anti-Neu5Gc antibodies in rheumatoid arthritis patients, but found no connection there. Rheumatoid arthritis patients do not have elevated levels of anti-Neu5Gc antibodies.
Their paper has not yet been cited by any other papers. It looks like the investigation of Neu5Gc-mediated autoimmunity is at its very beginnings.
Jim Beecham’s Experience
Jim Beecham, MD, responded to my previous post with a personal story:
I read with interest your post about Neu5Gc. I am anxious to read Part 2 which I understand is coming. Meanwhile I have been doing a little research on the subject.
I suffered badly with childhood asthma, and I still get a sort of asthmatic tightness of my breathing once in a while. In the past few weeks have I realized this is on days after I eat cheese and/or beef. This has ceased upon my cutting out red meat and dairy this past week.
I also get hypothyroid symptoms of cold face and backs of hands from time to time. I wonder if this is also linked to Neu5Gc …
In a second comment Jim added:
Here’s another thought re: Neu5Gc…which I cannot prove but think is likely.
When an upsurge of titer of anti-Neu5Gc antibodies float in body fluids, they have opportunity cause inflammatory reaction.
One researcher postulated this mechanism for hemolytic uremic syndrome.
My own experience is I develop a groin ‘heat rash’ type reaction and irritable bladder a day or so after eating too much cheese and red meat.
Jim’s personal experiences add further evidence that Neu5Gc-driven inflammation and autoimmunity is a real phenomenon.
The paper linking Neu5Gc to hemolytic uremic syndrome is [6].
Conclusion
There’s an excellent chance that Hashimoto’s hypothyroidism is brought about by a complex of factors:
- An infection in the gut by bacterial pathogens that acquire Neu5Gc from food (primarily beef and pork) and incorporate it into their cell walls.
- A leaky gut that (a) allows Neu5Gc from food to enter the body for subsequent incorporation into human cells, such as thyroid cells, and (b) creates either a systemic invasion of Neu5Gc-bearing gut pathogens, or a “metabolic endotoxemia” in which Neu5Gc-bearing cell wall components of gut bacteria enter the body, triggering formation of high-affinity anti-Neu5Gc antibodies.
- Significant consumption of beef and pork, providing the Neu5Gc to drive the autoimmune process.
If this is the case, then the strategy for overcoming Hashi’s would involve:
- Improving gut barrier integrity and mucosal immunity,
- Normalizing or diversifying the gut flora, and
- Reducing dietary Neu5Gc by replacing beef, dairy, lamb, and pork with seafood and bird meats.
Neu5Gc-mediated autoimmunity does not play a role in rheumatoid arthritis, but it may play a role in other autoimmune diseases. The most likely organ to be affected is the gut, which is directly exposed to food; endothelial cells, which line blood vessel walls, and immune cells which circulate in blood, as blood is the next location after the gut exposed to food molecules entering the body; and lastly organs which interact closely with the blood, such as the thyroid. Hemolytic uremic syndrome is a condition of endothelial cell dysfunction.
So: it looks like reduction of mammalian meats, replacing them with seafood and bird meats, may be a prudent part of a “Hashimoto’s protocol.” In autoimmune disorders affecting the gut, blood vessels, or immune cells, it may be worth trying a 30-day elimination of mammalian meats.
Perfect Health Retreat
We have a few spots remaining for the May 2-9 Perfect Health Retreat, and will soon be taking reservations for the October retreat, either October 3-10 or 10-17 (or both). If you are interested, visit here for more info or email me at paul@perfecthealthretreat.com.
References
[1] “Generation of Antibody Diversity,” in Alberts B, Johnson A, Lewis J, et al., Molecular Biology of the Cell, 4th edition, New York: Garland Science; 2002, http://www.ncbi.nlm.nih.gov/books/NBK26860/.
[2] Harvey HA, Swords WE, Apicella MA. The mimicry of human glycolipids and glycosphingolipids by the lipooligosaccharides of pathogenic neisseria and haemophilus. J Autoimmun. 2001 May;16(3):257-62. http://pmid.us/11334490.
[3] Severi E, Hood DW, Thomas GH. Sialic acid utilization by bacterial pathogens. Microbiology. 2007 Sep;153(Pt 9):2817-22. http://pmid.us/17768226. Full text: http://mic.sgmjournals.org/content/153/9/2817.long.
[4] Eleftheriou P et al. Prevalence of anti-Neu5Gc antibodies in patients with hypothyroidism. Biomed Res Int. 2014;2014:963230. http://pmid.us/25003133.
[5] Varki A, Gagneux P. Multifarious roles of sialic acids in immunity. Ann N Y Acad Sci. 2012 Apr;1253:16-36. http://pmid.us/22524423. Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357316/
[6] Löfling JC et al. A dietary non-human sialic acid may facilitate hemolytic-uremic syndrome. Kidney Int. 2009 Jul;76(2):140-4. http://pmid.us/19387473.
via this link:
Interesting. I think though, in my case of undiagnosed Celiac and multiple food poisoning episodes, I had leaky gut and poor functioning of the cleansing waves of the small intestine, my diet of occasional meat and pork didn’t help but certainly didn’t cause Hoshimoto’s. BTW- the food poisonings I had were from seafood!!
Very interesting Paul, thanks for delving into the emerging evidence for us. I love seafood and would be perfectly happy eating it every day. However, my methyl mercury levels are high and I appear to be a slow mercury detoxifier. I also have low free T3, despite normal free T4. My understanding is that mercury can interfere with the conversion of T4 to T3. Although I don’t have strong symptoms of hypothyroidism (except perhaps insomnia and low body temp), my experience and that of others I have read about would seem to indicate that those with hypothyroidism would have to be careful with the consumption of high mercury ocean fish, along with reducing other mercury exposure of course. Leaves not too much to eat in the way of animal proteins. I guess just eggs and poultry and low mercury fish (no more tuna sushi for a while 😥 )!
Thanks Paul – this is really interesting. It may explain why I still have high TPO and TG anti-bodies despite a strict gluten free diet. When I followed an auto-immune paleo diet they fell by about 30% great – but TPO still over 1000. Since my diagnosis 5 years ago, when I was asymptomatic, my thyroid has got progressively damaged and I now need to take daily thyroxin, which I do well on and convert well to T3, so consequently have no hypothyroid symptoms.
Dairy and cheese seem to be a trigger for dishydrotic eczema which I get on my hands within 2 – 3 days of eating.
I’ve always felt better eating poultry and seafood and eggs for protein, hard to explain – more energy, lighter.
Looks like I’ll be doing another experiment with my diet – red meat free. I’ll get some baseline thyroid tests first though.
I’ve just got my thyroid retests, prior to the red meat free challenge my TPO antibodies were 465, (down from a high of 1600 a few years ago). Dairy free seems to help. After 3 months of using almost only poultry and fish and eggs as my protein they are down to 385 so an improvement, but still high. I’ve been on a stable dose of thyroxine for the last 3 years so my thyroid function seems to be stable and not deteriorating.
Very interesting. I appear to develop a small goiter currently. I have thyroid symptoms for years now, cold legs, reflux, etc. I guess it is Hashimoto or SLE, I’ll go to a blood test this week. If it is Hashimoto at least I’ll know what to do. 🙂
If the red meat can provoke an auto-immune reaction, could it possibly be the cause of psoriasis as well?
I think that is unlike, but who knows. 🙂 Psoriasis works differently than Hashimoto: http://f1000.com/prime/reports/b/2/40/ keratin is attacked by the immune system and the IL17/23 axis is impaired because of genetic mutations. Sunbath can be a release, it downregulates that pathway. And there are new IL23 blockers which can help too.
This is very interesting. I too went gluten free six years ago after my Hashimoto’s diagnosis but my antibodies did not change. I went on Gaps twice and still no change in how I was feeling. The only thing that did change was my intake of organic red meat, pork and raw dairy. I now also have Graves. I wonder if this could be a big piece of the puzzle?
Just this week it occurred to me I’ve been forcing myself to eat red meat or lamb when not only do I not care for it, but feel it may be somewhat constipating. Red meat is so integral to the Paleo diet, that I’ve been including it only because it is said to be so healthy and essential. I’m going to leave it out for awhile, and stick to my fish and some chicken. I don’t eat much more than 6 ounces or so per day anyway.
Liz – did you go dairy free as well? I’ve heard some people’s antibodies decrease when they have gone dairy free (not for me though)
I’ve also been taking selenium daily – I feel better when I do, selenium can bring anti-bodies down too.
Juliane, I think the correlation between symptoms (their severity) and antibody levels is stronger for TPO than it is for TG. And even for TPO, it could be off due to delayed or lagging response or for other reasons that we don’t fully understand. In fact, reading the article cited by Paul, it seems that Neu5Gc IgG is a better biomarker than either one and could certainly replace TG, which has always been a bit iffy. And yes, I agree, most people I know saw their symptoms improve going dairy-free and I don’t think it’s due to the placebo effect.
Hello Paul,
Thanks for the great research and analysis. I have a question. Is neu5gc found in fats as well? Would an autoimmune elimination diet still get to use ghee or beef tallow? Is it specifically the proteins that need to be eliminated, or the fats as well?
Thanks!
Hi Nick,
It’s found on cells and extracellular matrix. Butter should be fairly safe, definitely clarified butter/ghee would be.
Would bone broth from chicken therefore be preferred to those at risk compared to bone broth from cattle? It would be a good reason to use the chicken feet my butcher gives away for free! Thanks in advance for your assistance.
Thanks a million!
Do you think Neu5gc is found in Armour and other NDT medications?
I don’t know. It would be a good question to ask the manufacturer.
I had the same question, I cannot find any info about how these medicals are produced.
There is about 3-4% in salmon and dairy (except goat milk products) and 20-40% in red meat and goat milk products. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC218710/bin/pnas_2131556100v2_index.html I think fat has a high content too, since it was made from fat cells, which have cell surface sialic acid too.
Is it possible to be tested for levels of anti-Neu5Gc antibodies? And does it seem just as possible that Neu5Gc could play a role in the development of autoimmune diabetes? As a type 1 diabetic, I’m always looking for answers. So if those of us with autoimmune diseases (I also have moderately high TPO and TG antibodies, as type 1s often do), if possible, would it make sense to first test for anti-Neu5Gc antibodies before altering diet?
Another question- I’ve read somewhere (I can find it if anyone wants to know) that vaccines often were cultured in or maybe even contain traces of various animal elements (cultured in bovine serum, chicken embryo, etc). I have absolutely no idea and no special training to be drawing any conclusions about this but it just popped into my head. I don’t know the mechanism of how vaccines work but is it possible that they could contain traces of Neu5Gc and possibly be another source of autoimmunity? Not sure if that’s even possible…?? Please enlighten me on this in case I’m way off with this thought.
Also- where’s Mario Iwakura’s comment on this?? Very curious what he makes of this!
Thanks for sharing your research and insights here with all of us Paul!
KH
This is where I saw ingredients used for making vaccines:
http://vaccines.procon.org/view.resource.php?resourceID=005206#header_dtap
Actually egg is safe, but vaccines can contain beef related things, so you are right, they can contain Neu5Gc as well. This is interesting, maybe vaccines are not as safe as they claim. 😀 Btw. the basic mechanism behind them is add a low amount of toxic material, which causes some cell death in the vicinity. This alerts the immune system which find the fragments of the pathogen which causes a B-cell response which will result in memory B-cells. In theory they can find Neu5Gc too and develop antibodies against it, which can cause Hashimoto, but this is just theory without evidence. Actually there is genetic defect in every autoimmune disease as far as I know. I read in depth about 15 so far.
Glad to hear ghee is safe! Phew. How about Great Lakes Gelatin?
Interesting article thank you. Do you think bone broth from these animals would still be ok ?
Certainly not. Not even gelatine and such products…
Paul amazing analysis, as always. Thank you!
This is really overwhelming! I am in a bit of shock though!
Paul, few question that maybe you can help clarify:
1) Does this study influences the PHD recommendation?
2) How should one address the red meat in the diet? Should one cut red meat all together? Should one reduced to a few times per week?
3) What are your suggestions to both people with autoimmune disease and for people that do not suffer from autoimmune?
4) Does this mean that, for people that do not suffer from autoimmune disease, the consumption of red meat could eventually make then autoimmune?
Sorry for all the questions. At this moment I am confused about the type of meat (if any) I should consume.
Kind Regards
/Hugo
I think if somebody has a genetic defect which makes them susceptible to Hashimoto, then the consumption of red meat should be completely avoided. If they don’t have this kind of genetic defect, then there is no problem. But I assume there are no tests available to filter out these people…
Hi Paul,
Thanks very much for this series. I’ve learned a lot.
Hashimoto’s aside, I still wonder, should mammalian foods / food products be reduced simply due to the increase cancer/CVD risk of inflammatory neu5gc? The idea that this molecule gets incorporated into human tissue and causes a continual inflammation (for what duration?) is worrisome.
Do you think the effect is strong enough to change any of your dietary recommendations?
Regarding the recent study that triggered this discussion — you mentioned it was an artificial scenario — I tend to agree, but could you elaborate?
Thanks again!
Ryan
Hi Ryan,
It’s not inflammatory unless you have anti-Neu5Gc antibodies, and you need certain gut bacteria to get the antibodies. I think ultimately we want to have clinical testing for anti-Neu5Gc antibodies and cut down on red meat if you do have them, cut down more if the titers are higher.
For now, I think we can say that Hashimoto’s patients should cut down on red meat. I’m not sure it makes sense to go any further.
By “certain gut bacteria”, do you generally mean certain large intestinal flora, or certain small intestinal flora?
Also, do we know anything (beyond the list of Neu5Ac-incorporating bacteria you gave in the first part of this series) about which genera of gut bacteria would be responsible?
Hi Eric,
It’s probably most often small intestinal flora, or even respiratory tract (mouth, esophagus) bacteria.
Possibly it should be described as an infection.
No, there doesn’t seem to have been much investigation on this topic.
But poultry and seafood’s are higher in polyunsaturated fats, which in higher doses are inflammator, even omega 3s can be taken to excess. There seems to be a catch22 here. Any I know an ex vegan who’d love to know if sticking to fish and poultry are preferred over red meats. What about… goat?
Goat is a ruminant like beef or lamb. Fish and poultry are preferred in terms of autoimmunity, but fish and ruminants are preferred for fatty acid composition. So pescetarian may be the optimum.
Hello Paul,
Please could you give your point of view on the heavy metals contained in fish for pescetarian ? And how to get rid of heavy metals (if it’s possible).
Another about legumes. So many debates on this topic : i recently noticed you were more opened on those food consumption. But for safety , what is the right way to prepare for example lentils or red lentils ? I’ve found some pasta lentils here, made with lentils flour.. could it be suitable ? Thanks or your answers.Regards,
Penny
I think if you try not to eat excess omega3 and keep the recommended omega3-omega6 ratio, it is okay. You can add omega3 with olives and flax seed if you don’t want seafood high in heavy metals. Flax seed is a goitrogen, so maybe you don’t need that. Sometimes it is better to know less. 😀 Btw. if you don’t have thyroid problems, you don’t need this kind of diet.
I have Hashimoto s and other symptoms including tremors. I always thought my Hashi’s was, for the most part, under control and a non issue. I began keeping a food journal during a downturn in my health and realized I felt weak and more tremorous after eating beef and pork; pork seems to be worse. IGG food testing did not pick either of these up., although chicken did show up. Beef and pork do not cause any obvious GI discomfort; chicken does. I am eating mostly fish along with lamb, turkey and duck right now. The AIP has been helpful and harmful, possibly because it has been too low carb, resulting in too rapid weight loss. I’m exploring PHD, although, I have so many true sensitivities that it’s hard to implement any diet perfectly.
Many thanks for your work.
Tremor can be caused by vitamin B deficiency. Try out vitB, vitD, Zn, Se supplementation. These made me feel better. Another triggers are mold spores by me. I used to have black mold on the insulation of my window which worsened the symptoms.
Hi Paul,
After rereading this post, I’m feeling stunned. I recognize the research you cited is still preliminary. However, I feel that it may hold some answers for me. I’ don’t want to exclude all red meat from my diet without being tested for anti-Neu5gc antibodies. It has been several months since I made the connection between beef and pork and the exacerbation of my symptoms. I recently crashed after about 10 days on AIP. After listening to your podcast on Phoenix Helix, I recognized how low carb my diet was. I’m making necessary changes and starting to feel a little stronger.
Do I simply ask her to test for anti-Neu5Gc antibodies? Is there other blood work that should be ordered with it ? I’m waiting on test results now (7 vials worth of blood)so, some of it will already be covered.
Thank you, Paul
I think you may be a life saver,
Claire
Makes me wonder if this would have any implications for the use of Armour thyroid as it is derived from pigs.
just curious– is vegetarianism ever right for anyone? for specific conditons?
http://m.theatlantic.com/health/archive/2015/01/joint-pain-from-the-gut/383772/
Worldwide Links between Proteus mirabilis and Rheumatoid Arthritis http://www.omicsgroup.org/journals/worldwide-links-between-proteus-mirabilis-and-rheumatoid-arthritis-2167-7921.1000142.pdf
“just curious– is vegetarianism ever right for anyone?” – It is hard to tell.
This is interesting, because the Pagano psoriasis diet, which a lot of people claim is effective if followed carefully, is basically removing nightshades, red meat, sugar and a few other items. I have psoriasis and I tried a modified paleo or PHD version of this diet without success. Basically it was PHD without nightshades, I ate a lot of red meat because that’s what the PHD recommends, and I figured that Pagano’s restrictions to fish and fowl were nonsense. Red meat is good for you, etc.
So it’s interesting that there could be something to that restriction to chicken and fish, and that these new potential recommendations for Hashimoto’s mirror old recommendations for another autoimmune disease.
Anyway, I’ll now try a stricter version of the paleoized version of the Pagano diet.
This is truly an eye-opening post. We’ve been hearing about Neu5Gc and cancer but not about the connection with autoimmune hypothyroidism. But like the research article (Eleftheriou et al) says, it’s not clear whether Neu5Gc is a “causative factor” or a “parallel result” of the onset of Hashimoto’s. This could be like high BCAA levels prior to diabetes onset (presumably parallel rather than causative). Or it could be like the predominance of provotella copri in gut flora prior to RA (causative at least for the inflammation phase of RA).
Plus, there seem to be some questionable facts or errors in the article: (1) Table 3 (p. 4) may have switched medians for minimums — these numbers just don’t make sense, e.g., the median for Hashimoto’s can’t be 0.1; (2) Hashimoto’s accounts for far more than 50% of hypothyroidism, even in a maritime country like Greece where excess Iodine intake may trigger many non-autoimmune hypo cases; (3) RA antibody ACPA is seen in >95% of patients and is very accurate, not ~67% – that would be more like for RF only; (4) the non-normal distribution for females is not due to the predominance of subclinical hypo but because Neu5Gc skyrockets in symptomatic cases of Hashimoto’s, as in a lognormal right tail distribution.
But what gives strength to the argument is the staggering association with Hashimoto’s and sheer correlation between Neu5GC and TPO (Figure 2). There’s actually higher correlation for Hashimoto’s with IgG Neu5Gc than with either TPO or TG (Neu5Gc might as well debut as an official antibody and replace TG, the weaker biomarker). And the finding about IgM Neu5Gc going up while IgA remains low, suggestive of “compensating” for the impaired IgA defense by IgM and IgG; immunodeficiency may be part of all this.
Congrats on another insightful article, Paul. Given your diet, such a finding may not be welcoming. However, you’re concerned only with letting the data speak for itself, something which we can’t say for many in the Paleosphere with their skin in the game. Your integrity indisputable.
Thanks Zorro, great comment.
This is intriguing. I quit eating red meat and pork about 30 years before I was diagnosed with Hashimoto’s, and I think I’ve had lamb once in my life.
I read various bloggers who claim to have “reversed” Hashimoto’s on different diets. I realize that you have to figure out what works for your body, but it would be good to find the common denominators in diets that help Hashimoto’s patients.
You should avoid goitrogenic substances and Neu5Gc and supplement with Zn, Se, vitB, vitD. That’s all I know of currently. https://en.wikipedia.org/wiki/Goitrogen
Paul,
I’m a 30 year old male, been paleo (thanks to you) for 4 years, and was diagnosed with severe Hashimoto’s a decade ago. I’ve now avoided mammal meat for 6 days and it’s the biggest improvement in health since starting to eat larger amounts of fat. Bloating is reduced, energy is up, muscle fatigue is way down, lust for life is coming back, and so far perfect BMs. The “health buffer” is improving each day and just to jerk some tears I can hold my 4 month old baby girl without putting her down every 5 minutes. Please, continue to add value to people’s lives. I hope to meet you someday. Be well and thanks again!
Craig, thank you, very happy to hear you are better! Also glad to get corroboration that mammal meats are a factor in Hashimoto’s. All the best to you,
Paul
Paul, I’m having a similiar experience to what Craig described. I’ve been off mammal meat now for going on a week and the improvement in how I’m feeling is dramatic. I can’t thank you enough for your help.
Mary
Please forgive my ignorance, but are properly prepared beans okay for hashis? I’m considering cutting out red meat after reading this, and really need to get some protein sources figured out (along with RS, etc). Thanks in advance!
Hi Kati, I would go with seafood, freshwater fish, and birds (chicken, duck) as my main protein sources, but lentils, split peas, and possibly beans are acceptable on PHD with long soaking followed by thorough cooking in a pressure cooker.
If you’re going further down the list of acceptable legumes than lentils and split peas, wouldn’t hulled cowpeas (e.g. yellow mung beans) be preferable to beans? They appear to be lower in saponins, isoflavones, and other heat-stable antinutrients.
Also: Wouldn’t hulled lentils (e.g. red lentils) be preferable to unhulled lentils?
Paul,
I read this and it is interesting, but I am wondering if you can make a leap of judgement here. I was at the endocrinologist today and I have very high Grave’s antibodies. I had radioactive iodine, but during my pregnancy began to produce these antibodies again, and as my doctor stated, decided not clear themselves these past five years. I do have an immunodeficiency which leads me to think I can be more susceptible to gut bacteria. Since I am hypothyroid post ablation, with high graves antibodies, is this enough reason to stop eating red meat?
Thank you,
Amy
Hi Amy,
I haven’t seen evidence linking red meat to Graves, but I think it could be worth an experiment. Try it for a month and see if you feel better. If you have a good source of seafood it shouldn’t be too arduous. A month should be enough to let antibodies go down, if the red meat is involved.
Hi,
this is very interesting. I’m wondering if there is any research in what was first, the Hashimoto or the Neu5Gc- Antibodies. Or is this a hen-egg question?
Thanks.
What about that protein powder which is made from beef? I guess that is a no no
Hi Paul !
What about the use of Armour thyroid ? (since it’s derived from pigs)
This is facinating especially because it makes sense with a recent client of mine, who had Hashimotos and reversed it by eating precisely according to the PHD with not too much red meat but more fish and foul. And she no longer requires Thyroid medication and her blood work came back normal after one year! Thanks Paul!
Two questions that might shed more light on the question:
1. Do we see Hashimoto’s frequently in hunter-gatherer populations who eat lots of mammalian meat?
2. Do vegetarians and vegans with Hashimoto’s have similarly high levels of Neu5Gc antibodies? If so, where is it coming from since it’s not coming from red meat?
Yes, excellent questions. I’m not aware that anyone knows the answers.
Hello all, I am not sure if this is the correct post to put this question but here goes.
I am thinking of switching from Levothyroxine to Armour and I’m in the UK. Has anyone any advice you can give me please?
My advice – don’t switch; combine the Armour and levothyroxine, reducing the dose of levothyroxine as you add in a small amount of Armour.
thanks Paul, that’s very useful. Am I right in that Armour contains both T4 and T3 whereas Levothyroxine contains only T4 and one time you recommended me to take some T3 also which is impossible to get in the UK. So I concluded it may be better to switch to Armour as it is more nature. Useful to know to switch slowly though.
Many thanks
Shaz, I can’t and won’t have made any such recommendations. Some people benefit from a bit of T3 in addition to their T4, for most it’s unnecessary and liable to do harm. Only your doctor can make recommendations in regard to T3. Regardless, if you do take T3, you should experiment to find the lowest dose that relieves your symptoms. Overdosing T3 is a major problem. Also, Armour has too high a ratio of T3 to T4, so don’t take it alone.
Doctors don’t like Armour because the doses can vary from batch to batch. They focus on T4 because it is the only thyroid hormone that is made exclusively by your thyroid. T3 is made from T4 and happens both in the thyroid and outside the thyroid. Since TSH goes down (the hormone that requests T4 from the thyroid) when T4 is supplemented, even synthetic T4, most doctors are primarily interested in giving you the right dose of T4 so that TSH will be within acceptable range, and trusting your other organs to synthesize the T3. At the same time, the thyroid does produce T3 and to have a thyroid that can’t function fully like one suffering from Hashimoto’s, you will lose some ability to make T3. Yet this is where you balance the goals of accurately keeping TSH down and making sure you have enough T3. So when it comes to treating symptoms, it makes sense to see if some T3 supplementation (like with Armour) makes you feel better, but like Paul said, not by eliminating synthetic T4 supplementation.
As far as my personal recommendation, avoid brand name Synthroid. They cannot guarantee their product is gluten free. Many generic levothyroxines can, so call your pharmacy and hey will be able to tell you.
thank you Ben and Paul for your helpful comments.
😆
I am 64. I was diagnosed with lupus when I was 29. I had Hashimoto disease when I was 44. My thyroid was killed. What diet would you recommend?
Hi Tess,
I would recommend our diet, but with less beef, lamb, and pork and more fish, seafood, chicken, and duck.
It can affect transplantation too, at least xenotransplantation: http://www6.tau.ac.il/karavani/images/PDFs/13%20Potential%20impact%20of%20the%20non%20human%20sialic%20acid%20N%20glycolylneuraminic%20acid%20on%20transplant%20rejection%20risk.pdf
This is very interesting post. How neu5gc antibodies relate to hashimotos antibodies? Are you saying that beu5gc gets into thyroid tissue and both too and anti neu5gc antibodies are created causing further thyroid damage?
If somebody has tpo antibodies but no symptoms how your theory could be tested?
Should one test for tpo stop eating meat and test again after month?
Do you recommend to stop eating meat completely or just limit it to let’s say once a week? Why the functional medicine doctors don’t talk about neu5gc?
It seems like you are one of the only ones that mentioned this topic.
It’s about a year old topic and a single article is not enough. We are waiting for other articles and studies which confirm that mammalian product free diet keeps people symptom free in Hashimoto’s disease.
Ofc. you can try it out if you want, it cannot do much harm. Just don’t eat any mammalian product: red meat, fat, gelatine, milk products, etc…
So lets say Neu5gc has a connection to Hashimotos. Would removing mammal meats got rid of thyroid antibodies?
Do you recommend to stop eating meat at all or 1 a week is ok? How about diary?
If antibodies would disappear would it be possible to reintroduce mammal meats at later time?
Completely off topic, but I don’t know where else to ask.
What’s the word on GMO foods, specifically salmon?
Everyone around her going postal on the subject.
The media is doing what they always do, create another crisis.
Hi erp,
I assume you’re referring to “AquAdvantage salmon”?
In that case: The genetic engineering is intended to increase growth rate by adding genes from other fish species which control growth hormone levels. This is probably much safer than, say, genetic engineering intended to increase toxicity to pests by adding in genes from other species which code for toxic proteins!
Best,
-Eric
Eric, thanks for the reply, but are you saying yes, the salmon is okay for us geezers or it’s not as bad as it could be?
It’s about a third of the price as the other kinds of salmon, a very popular feature here in retirementland.
Hi erp,
My guess is that it’s okay (although I don’t know with 100% certainty). I would probably eat it, unless someone I trust (like Paul) raised a credible objection.
Best,
-Eric
Hi erp,
Just to further clarify: I’m not saying the GMO salmon is just as good as fresh wild-caught salmon… Rather, my guess is that it’s a sensible compromise given the massive price reduction.
Best,
-Eric
Thanks Eric. You have reassured the 80 somethings around here that it’s safe-ish. Perhaps Paul will do a post on GMO since it’s so much in the news now.
As for wild-caught, I remember some years ago that there was scare about mercury in swordfish and also concerns about pollutants in lobsters, cod, tuna and other ocean going fish?
It is really difficult to know what to believe now that scientific research has become a follow-the-money operation.
It would be great if Paul were put in charge, so we could have complete trust in what we see in the media.
Hi erp,
I’m glad I could provide some reassurance.
The concern with wild-caught fish is primarily for fish high on the food chain (like swordfish, tuna, etc.). It’s not much of a worry for salmon.
Best,
-Eric
I have Hashimoto’s and have been planning on following the AIP, but am conflicted since I’ve read this. To follow that protocol without red meat would be terribly hard.
Is it enough to eat PHD and only exclude red meat + dairy but still include nuts, eggs, nightshades and ghee?
I would prefer to do this version of the PHD instead of the AIP, but if I have to I guess I could do a combination.
Is it important to exclude eggs, nightshades and nuts as well if you have Hashimoto’s?
Thankful for a reply!
Hi Mary,
Yes, I would favor PHD without mammalian meats over AIP. There is no reason to exclude egg yolks, nightshades or nuts unless you have a sensitivity reaction to them.
Best, Paul
Thank you so much, Paul! I will do that then, can’t wait to see how it goes. I’m not feeling all too well at the moment.
A second question, my sister-in-law has lichen sclerosus and polyneuropathy (feet), would she benefit from following this protocol or does she need to do the AIP or simply the regular PHD?
Thank you again! I really appreciate it.
Hi Mary,
I would recommend that she follow the regular PHD for a few months, and then consider tweaks to see if they help. PHD is a good baseline to adopt before experimenting.
Best, Paul
That’s great! I will tell her. Thank you for your advice!
All the best,
Mary
When people say they feel better when they stop eating “red meat”, it’s hard to know why they got that result.
Factory-raised meat contains contaminants and is not as health as 100% grass-fed meat. Many people feel better when they switch from factory-raised to grass-fed red meat.
Another confounder is mold contamination. We live in the San Francisco Bay Area, and this winter all the locally-raised red meat we’ve tried, from multiple farmers, has high levels of mold contamination, probably because of the large amount of rain and small numbers of processing plants. We’ve started buying mail-order to get red meat that we can eat without feeling bad afterwards. The local chicken we’ve tried didn’t have this problem, but was a very small sample.
We really need clarity on the meat source and possible confounders; to blame all of the negative effects of red meat on Neu5Gc seems unwarranted, given the strong possibility of confounding by contaminants.
I ate red meat and pork (sausages, hamburgers, steak) almost everyday for six weeks this past summer. We barbequed almost everything and without realizing it, I noticed my Hashi symptoms improved. That’s right. Improved. By a lot. I also had beer with those meals. And I ate bread and buns and butter, too. I also ate seeweed, Nori sheets, a few times a week. I had very little falling hair, which is my signal that the Hashi’s is being kept at bay. Since then I tapered off the meat, and now have the Hashi’s storm back. A German article I read on Hashimoto’s says iron is important. I started thinking that my heavy meat diet with pork offered a combo of iron and high selenium and iodine. I am going to experiment now, and will go back to eating more beef and pork and see what happens. I also find that taking Selenium supplements makes my hair fall out more after a few days. Over a year ago, I also stopped taking replacement thyroid hormone because it made everything worse. I should also say that my thyroid numbers are borderline, but I have high antibodies. I didn’t check the antibodies after the summer. Maybe should have. Anyway, that’s my experience with beef and pork.
So, when we say to eat little of red meat, what do we mean by that? Is it 3 times per week? Once a month? A year? What about organ meat?
Hi Julz,
Reducing red meat (i.e. meat or milk from mammals) is only of value in certain autoimmune conditions. The optimal approach to autoimmune conditions is not well understood, but a prudent approach might be to periodically try total elimination for >1 month periods to see if you feel better. It typically takes several weeks to clear antibodies and time to clear Neu5Gc from cell surfaces, so you probably at least a month to give the approach a fair test. With repeated going on and off you may get a feel for the symptoms red meat generates and the timing of them, and that can help you find a manner of eating that minimizes symptoms.
Best, Paul
In recent months, Dr. Steven Gundry has been mentioning Neu5Gc quite a bit on his podcast and in interviews. (It seems that he discusses it in his most recent book.)
This is the first I had heard of Neu5Gc. I was dismayed to learn about it, because the variety of food that I can eat these days without having bad reactions is already limited due to various food allergies (such as shellfish) and sensitivities. (I have bad reactions to grains including oats and corn, to nightshades, to all legumes – even peas, green beans, chocolate, and guar gum -, to most “high lectin” plant foods even including butternut squash and cucumbers, to goitrogens due to my hypothyroidism, to all coconut products like coconut oil, coconut flour, and coconut milk; plus one year ago, suddenly every plant food with moderate or high Vitamin A such as spinach, carrots, chard, and sweet potatoes immediately started to cause me to have dry facial skin, “beardy” growth on my face (I’m female), and a bad rash around my neck, so that newest development really cut down on the vegetables that I can still eat.) Additionally, my backwater area of the country is bad for supermarket food choices beyond the unhealthy American “basics” (there are no Whole Foods, Trader Joe’s, etc. within an hour and a half drive).
Most importantly, I have good reason to be extra-cautious about promoting ovarian cancer growth; therefore, 2 years ago, I dropped all added sugars and all sweets, and now I am wondering if I should go from being having been low-carb (with 8:16 time-restricted eating) for the past few years to being fully ketogenic in my diet (maybe adding in a 24-hour fast once or twice a week). Therefore, to take away beef, dairy milk, and dairy cheese from my food options due to Neu5Gc’s promotion of cancer would be taking away most of what I can eat (without having bad reactions) these days.
Usually when I hear about something interesting regarding nutrition, I think, “I wonder if the Jaminets ever addressed that!”, so I came to the PHD site to see if Neu5Gc had ever been mentioned here, and I found this post from 2015.
In the past few months, in various YouTube interviews, I have heard Dr. Steven Gundry say that Neu5Gc is not in certain fermented sausages made with mammalian meat through traditional processes — for example, he mentions sausages from a certain region of Andorra — because bacteria in the fermentation process can apparently consume the Neu5Gc. He connects having a low level of Neu5Gc in one of their main mammalian animal foods to the very high life expectancy of people living in that region of Andorra (I think they are the people living in the mountainous area, not the sea-level area). He cautions that not every type of sausage is “fermented”, so meat sausages that are typically available in the US are usually not fermented.
Tonight I found this on his website: “Every time we eat Neu5Gc-containing foods or drink Neu5Gc-containing milk, we instantaneously make antibodies to Neu5Gc. We believe it is a foreign substance, and we make antibodies against it, just like you make antibodies when you get a vaccine. Though, we used to think that, well, we didn’t think, we know there’s a strong association between red meat eating and heart disease, arthritis, memory loss, dementia, and cancer. Very strong. Now, I’m the first to say association does not mean causation. But here’s the exciting new news in the book. We now know the mechanism of causation. Neu5Gc, because it’s so similar to Neu5Ac, can be incorporated into the lining of our gut, the lining of our blood vessels, the lining of our blood-brain barrier, and the lining of our joints replacing Neu5Ac. So now we have an antigenic compound that our immune system hates lining these structures and our immune system attacks it, causing inflammation in our blood vessels, inflammation in our brain, inflammation in our joints. And Neu5Gc is used by cancer cells to produce local inflammation that they actually thrive in. So it’s no longer a case of association. It’s now a proven causation, and the mechanism is startling. Now, here’s the good news. There’s a workaround, but you’re going to have to read the book to find it.” source: https://drgundry.com/gut-check-transcript/
Apparently the “workaround” he was “teasing” in that excerpt is eating fermented mammalian foods. Fermented meat such as the Andorran sausages may be hard to find in the US, but it seems that Dr. Gundry is claiming that cow-milk yogurt is also relatively free of Neu5Gc: Tonight, I found an Instagram post of his from a couple of months ago: “Neu5Gc is a gut barrier disrupter found in the blood vessels of beef, lamb, pork, bison, and their milk. Good news: Neu5Gc is destroyed during the fermentation process! So if you’re consuming cow milk or meat products, opt for fermented options like plain yogurt or an occasional fermented sausage.” source: https://www.instagram.com/drstevengundry/p/C2K0YddRhU1/?img_index=1
My quick internet search tonight did not reveal any other sources for the claim that dairy yogurts are low in Neu5Gc. Perhaps his lastest book lists references for that assertion.
However, I did find a table in a journal article from 2015 which says that the Neu5Gc content (μg/g) in various foods was tested to be the following:
butter: 0, whole cow milk: 2, cow-milk cheese: 10-22, goat-milk cheese: 43, lamb: 14, beef: 25-231, pork: 7-40.
Note that while fish and seafood generally have a score of 0, caviar (fish eggs) have a huge level of 445-530 of μg/g!
Unfortunately, fermented cow-milk yogurt is not on this list.
I was surprised that whole cow milk was reported to only have 2 μg/g, so it’s not such a stretch to think that after cow milk is fermented and turned into yogurt, the resulting level of Neu5Gc could be quite low.
In the article’s discussion section, the authors write, “We have demonstrated here that antibodies directed against the nonhuman sialic acid Neu5Gc can interact with metabolically incorporated Neu5Gc derived from oral intake and promote inflammation in a dose-dependent manner in the human-like Neu5Gc-deficient Cmah−/− mouse model. Furthermore, long-term exposure to such inflammation promotes carcinoma incidence in a target organ where Neu5Gc can accumulate; in the case of mice, it is detected in the liver, and in humans, it is detected more prominently in the colon, prostate, and ovary.” source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299224/table/t01/?report=objectonly
According to that article, Neu5Gc “promotes carcinoma incidence… in humans… more prominently in the colon, prostate, and ovary.” Therefore, it would seem that this may be something for those who don’t have Hashimoto’s hypothyroidism to look at more seriously, and consider limiting in the diet.
[By the way, while the following finding doesn’t, practically speaking, increase the variety of my possible food choices, I thought I’d quote a 2021 article that claims there is no Neu5Gc in dog or kangaroo meat. “We measured Neu5Gc in skeletal muscle and organ tissues from nine species using UHPLC and found that: (1) neu5Gc concentration in skeletal muscle was highest in goats (166 ± 48.7 µg/g protein), followed by cattle, pig, sheep, horse, cat and deer: >75% was conjugated. No Neu5Gc was detected in kangaroo and dog muscles; (2) total Neu5Gc in organ meats was generally about 2-54% higher than in muscle. Surprisingly Neu5Gc was absent in seven organs of female deer; (3) nine commercial ovine meat cuts contained similar Neu5Gc levels. Thus, red meat Neu5Gc concentration is tissue and species-specific and absent in muscle and organ tissue of some species. Our study provides guidelines for animal meat preferences for consumers and sheds light on the functionality of Neu5Gc.” source: https://pubmed.ncbi.nlm.nih.gov/33127222/ ]
Today I found an article on the ScienceDaily website describing a 2020 journal article by a Neu5Gc researcher named Vered Padler-Karavani who works at the Department of Cell Research and Immunology of Tel Aviv University.
I then looked up that researcher’s name in PubMed and found a few of her articles on Neu5Gc and human diet that I thought I’d list here.
Firstly, here is an excerpt of the ScienceDaily article which caught my attention:
“Researchers discover molecular link between diet and risk of colorectal cancer. Study based on extensive survey of nutrition conducted in France.”
source: https://www.sciencedaily.com/releases/2020/10/201022151749.htm
excerpt: “Researchers have identified a direct molecular link between meat and dairy diets and the development of antibodies in the blood that increase the chances of developing cancer. This connection may explain the high incidence of cancer among those who consume large amounts of dairy products and red meat, similar to the link between high cholesterol and an increased risk of heart disease. ….
Based on these findings and the quantification of Neu5Gc sugar in various food products from France, Dr. Padler-Karavani and her team created an index called the Gcemic index. This index ranks foods whose excessive consumption can lead to an increase in the antibodies — and possibly to an increase in the risk of cancer.
‘We found a significant correlation between high consumption of Neu5Gc from red meat and cheeses and increased development of those antibodies that heighten the risk of cancer,’ Dr. Padler-Karavani says. ‘For years there have been efforts to find such a connection, but no one did. Here, for the first time, we were able to find a molecular link thanks to the accuracy of the methods used to measure the antibodies in the blood and the detailed data from the French diet questionnaires.’
Dr. Padler-Karavani adds that this combination of methods allowed the researchers to predict that those who eat a lot of red meat and cheese will develop high levels and a different variety of the antibodies, and therefore may be at higher risk for cancer — especially colorectal cancer, but other cancers as well.”
1. Journal article from 2020 (this article was the subject of the ScienceDaily article)
“Association between Neu5Gc carbohydrate and serum antibodies against it provides the molecular link to cancer: French NutriNet-Santé study”
BMC Medicine
by Jean-Paul Soulillou, Vered Padler-Karavani, et al
source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510162/
A. excerpt of abstract: “High consumption of red and processed meat is commonly associated with increased cancer risk, particularly colorectal cancer. Antibodies against the red meat-derived carbohydrate N-glycolylneuraminic acid (Neu5Gc) exacerbate cancer in “human-like” mice. Human anti-Neu5Gc IgG and red meat are both independently proposed to increase cancer risk, yet how diet affects these antibodies is largely unknown. …. In a well-defined large cohort, we used glycomics to measure daily Neu5Gc intake from red meat and dairy, and investigated serum as well as affinity-purified anti-Neu5Gc antibodies. Based on 24-h dietary records, daily Neu5Gc intake was calculated for 19,621 subjects aged ≥ 18 years of the NutriNet-Santé study. Serum and affinity-purified anti-Neu5Gc antibodies were evaluated by ELISA and glycan microarrays in representative 120 individuals, each with at least eighteen 24-h dietary records. ….
Conclusions: We found a clear link between the levels and repertoire of serum anti-Neu5Gc IgG and Neu5Gc intake from red meat and dairy. These precise rational methodologies allowed to develop a Gcemic index to simplify the assessment of Neu5Gc in foods that could potentially be adapted for dietary recommendations to reduce cancer risk.”
B. excerpt regarding gender difference: “overall anti-Neu5Gc IgG responses showed a clear gender difference, with almost twice as much higher levels in men compared to women… Of note, the international correlation analysis showed increased incidence and mortality rates in men versus women in nations of high meat intake, but not in nations of low meat intake, supporting the hypothesis that higher meat intake leads to increased cancer risk due to higher Neu5Gc intake from meat that leads to higher levels of anti-Neu5Gc IgG.”
C. excerpt with potentially-practical information: “To translate these findings into practical personalized dietary recommendations, we calculated the gram of each food item that needs to be consumed to reach the ranges of average Neu5Gc consumed in the highest and lowest quartiles for both genders.
…In addition, we developed a Gcemic index as an easy tool to estimate the relative Neu5Gc content in different food items, based on the Neu5Gc content (nmol/gr) in each food item relative to the amount measured in beef (163 nmol/gr).
A Gcemic index of 1 means that daily consumption of 58 g of beef at most is the maximal Q1-Neu5Gc (9443 nmol/day), while daily consumption of at least 120 g is the minimum Q4-Neu5Gc (19,627 nmol/day).
Thus, one can consume 1–2 medium-sized beef steaks (225 g raw meat) per week to fall in Q1 range, while 4–5 steaks weekly is already at Q4 range.
A lower Gcemic index (or high inverse Gcemic index) means higher grams of food consumed to reach the Q1/Q4 ranges. For example, the Mozzarella Gcemic index is 0.03 hence almost 30 times more grams can be consumed compared to beef, while the Roquefort Gcemic index is 3.86 suggesting consuming only ¼ the amount of beef can reach Q1/Q4 range.
In general, cow dairy has the lowest Gcemic index, while sheep/goat dairy has the highest, while variable in meat. Arbitrarily dividing international meat cancer risk according to national intake of above/below 120 g meat daily (lowest beef amount in Q4) shows an increase of 3-fold in incidence and 2.5-fold in mortality in nations that consume > 120 g meat per day.
Interestingly, countries of high beef meat intake fall among the top 15 CRC incidence and mortality rates, including the USA, Australia, and France, as well as many counties in South America such as Argentina, Brazil, Uruguay, and Chile.
While the Gcemic index can provide a simple estimate on Neu5Gc content in food, a direct correlation between specific amounts of consumed food with cancer risk requires further investigation, to account for other common risk factors.”
D. excerpt: “accumulating evidences suggest that not all human anti-Neu5Gc antibodies are alike and the outcome of their effects on the disease can diverge from disease promotion to rather disease reduction and therapy. Apparently, these opposing effects could be related to both their induction source (elicited by diet or by immunization) and to the eventual quality of immune response.”
E. excerpt: Table S1 has the Neu5Gc content of various foods that are typically available in France. I (the poster of this comment on the PHD site) will highlight a few of them here.
Note: There are surely important differences between France and the US in terms of animal breeds and animal treatment (such as feed, medication, shelter, grazing), as well as the processing of animal-derived foods such as yogurt, cheese and milk, so these calculations may not be totally applicable to foods available in the US (or other countries), but at least directionally they might give some guidance to people who are seeking to lower their Neu5Gc exposure.
Neu5Gc average (nmol/gr)
Buffalo mozzerella cheese: 6
Rabbit: 7
Cow parmesan cheese: 11
Pig pork: 18
Cow yogurt: 18
Cow gouda cheese: 18
Cow milk: 21
Pig bacon: 31
Cow sausages: 32
Lamb: 67
Pig ham: 71
Cow powdered milk: 107
Pig cured ham: 140
Cow beef: 163
Pig sausage: 207
Sheep yogurt: 277
Goat feta cheese: 280
Pig liver: 409
Sheep roquefort cheese: 550
Note: These results do not entirely support what Dr. Gundry seems to be currently claiming (which I described in my above post yesterday) — something along the lines of ‘yogurt from animal milk is low in Neu5Gc because it is fermented’ — because French cow yogurt had a score of 18 in this article, but French sheep yogurt had a score of 277!
I will be interested to see what references Dr. Gundry mentions in his new book as supporting his claims.
2. Journal article from 2020. It was from a special issue of the journal Frontiers in Immunology which contained a number of papers on Neu5Gc.
“Human Antibodies Against the Dietary Non-human Neu5Gc-Carrying Glycans in Normal and Pathologic States”
editorial by Jean-Paul Soulillou and Vered Padler-Karavani
source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390827/
excerpt from the editorial: “This Research Topic embeds a unique collection of papers summarizing current knowledge and remaining open questions regarding the possible consequences of this ongoing immune conflict between anti-Neu5Gc antibodies and Neu5Gc-glycans, during normal and pathological states. ….Altogether, this special issue is a major contribution to increase awareness of this very complex research related to the immunogenic Neu5Gc dietary carbohydrate in humans and its potential involvement with multiple human diseases.
….While most mammals commonly express the two forms of sialic acids, N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), humans cannot synthesize Neu5Gc due to a loss-of-function mutation in the CMAH gene, which encodes the enzyme responsible for its synthesis. Consequently, Neu5Gc is immunogenic in humans, leading to generation of antibodies against various presentations of Neu5Gc-glycans. These antibodies appear in the first months of life and coincide with dietary intake of Neu5Gc (e.g., red meat and baby formulas containing cow’s milk). Co-existence of Neu5Gc and anti-Neu5Gc antibodies in humans may have detrimental consequences, and in recent years, a considerable amount of fundamental information on this subject has been accumulated. Diet-derived Neu5Gc can be absorbed by human cells and can be found at very low levels on the surface of endothelial cells and of oncogenic epithelial cells. This unique situation results in the expression of a non-self carbohydrate in the context of self, coined as a “xeno-autoantigen.” Together with circulating anti-Neu5Gc “xeno-autoantibodies,” a peculiar “physiological” condition of chronic antibody exposure may lead to in situ chronic inflammation, termed xenosialitis, eventually contributing to various human diseases.”
3. Journal article from 2008
“Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression”
Proceedings of the National Academy of Sciences, USA — Dec 2, 2008
by Maria Hedlund, Vered Padler-Karavani, et al
source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2596253/
abstract: “Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.”
I am back, just leaving some more information that I learned about Neu5Gc, in case it might help someone someday. 🙂
Main points:
– There is a researcher at the University of California who has been looking into Neu5Gc for many years, and apparently his findings on Neu5Gc in humans “may at least partially explain the link between high consumption of red meat and certain cancers.” — see “B” below.
-Consuming red meat may exascerbate disease severity in people with muscular dystrophy due to the Neu5Gc — see “A” below.
-Neu5Gc may be relevant in rheumatoid arthritis, endometriosis, HIV, cancer, diabetes, macular degeneration, infertility, heart attacks, etc. — see “C” and “D” below.
The researcher’s name is Dr. Ajit Varki. His lab website is: https://cmm.ucsd.edu/research/labs/varki/research/index.html. Blurb: “The Varki lab (directed by Ajit and Nissi Varki) uses these new approaches, along with the traditional tools of molecular biology, biochemistry, genetics and genomics to investigate selected areas of Glycobiology. The present focus is on sialic acids, which are found at the outermost position on the glycan chains of all vertebrate cell surfaces and glycoproteins. Currently active projects are relevant to the roles of sialic acids in Viral and Bacterial Infectivity, the Regulation of the Immune Response, the Initiation and Progression of Tumors and Unique Aspects of Human Evolution. We are particularly intrigued to find multiple differences in sialic acid biology between humans and our closest evolutionary cousins, the great apes. These differences are a signature of the multiple cellular and molecular events that occurred during the last few million years of human evolution, and are relevant to understanding several aspects of the current human condition, both in health and disease.” Note that they study “the initiation and progression of tumors”.
They provide free pdfs of most of their research articles, which is great. Here is a page with their “Red Meat and Disease Risk” publications: https://cmm.ucsd.edu/research/labs/varki/publications/red-meat-risk.html
I have only skimmed their publications of the last few years, and I do not have the background knowledge to understand their work beyond a very simple level, but some of the things that popped out to me regarding Neu5Gc were:
A. “Metabolic incorporation of dietary Neu5Gc into human tissues in the face of circulating antibodies against Neu5Gc-bearing glycans is thought to exacerbate inflammation-driven diseases like cancer and atherosclerosis. Probing of sera with sialoglycan arrays indicated that patients with Duchenne muscular dystrophy (DMD) had a threefold increase in overall anti-Neu5Gc antibody titer compared with age-matched controls. …These studies suggest that patients with DMD who harbor anti-Neu5Gc serum antibodies might exac
erbate disease severity when they ingest Neu5Gc-rich foods, like red meats.” From a 2021 article in the American Journal of Pathology. source: https://cmm.ucsd.edu/research/labs/varki/_files/publications/a286.pdf
B. “Researchers at University of California San Diego School of Medicine say the loss of a single gene two to three million years ago in our ancestors may have resulted in a heightened risk of cardiovascular disease in all humans as a species, while also setting up a further risk for red meat-eating humans. The findings are published July 22, 2019 in PNAS. ….
…in consuming red meat, humans are also repeatedly exposed to Neu5Gc, which researchers said prompts an immune response and chronic inflammation they call “xenosialitis.” In their tests, human-like mice modified to lack the CMAH gene were fed a Neu5Gc-rich, high-fat diet and subsequently suffered a further 2.4-fold increase in atherosclerosis, which could not be explained by changes in blood fats or sugars.
‘The human evolutionary loss of CMAH likely contributes to a predisposition to atherosclerosis by both intrinsic and extrinsic (dietary) factors,’ wrote the authors, ‘and future studies could consider using this more human-like model.’
In previous work, the Varkis and colleagues have shown that dietary Neu5Gc also promotes inflammation and cancer progression in Neu5Gc-deficient mice, suggesting that the non-human sugar molecule, which is abundant in red meat, may at least partially explain the link between high consumption of red meat and certain cancers.
source: https://today.ucsd.edu/story/evolutionary-gene-loss-may-help-explain-why-only-humans-are-prone-to-heart-attacks
C. from a 2016 journal article in Molecular Aspects of Medicine: “… mechanistic explanation for the human propensity for risk of red-meat associated diseases that is consistent with most observations: metabolic incorporation of a non-human sialic acid N-glycolylneuraminic acid (Neu5Gc) into the tissues of red meat consumers and the subsequent interaction with
inflammation-provoking antibodies against this “xenoautoantigen”. Overall, we conclude that while multiple mechanisms are likely operative, many proposed theories to date are not specific for red meat, and that the viral and xenoautoantigen theories deserve further consideration. Importantly, there are potential non-toxic dietary antidotes, if the xenoautoantigen theory is indeed correct. … anti-Neu5Gc antibodies have tumor stimulating properties through induction of inflammatory processes. Importantly, we noted that the in vivo expression of diet-derived Neu5Gc in multiple epithelial cell types may serve to explain the well-documented association of red meat-associated increased risk of carcinomas in diverse epithelial tissues, such as the prostate, breast, pancreas, esophagus, and ovary …Neu5Gc incorporation from red meat can induce xenosialitis in vascular endothelium, and may contribute to red meat-induced aggravation of atherosclerosis and CVD. …Studies have even shown that a diet restricted in red meat can reduce rates of recurrence in patients diagnosed with early stage colon cancer …we believe that xenosialitis may represent the missing link that connects red meat consumption to other inflammatory diseases such as atherosclerosis, type 2 diabetes, rheumatoid arthritis, macular degeneration and possibly certain forms of infertility”
source: https://cmm.ucsd.edu/research/labs/varki/_files/publications/b175.pdf
D. Here is a short video presentation from 2011 by Professor Varki on sialic acids and Neu5Gc: https://www.youtube.com/watch?v=EU3yVbDpA_4
At minute 14:25, he has a slide with differences in humans and great apes in the incidence and severity of many different biomedical conditions (including rheumatoid arthritis, carcinomas, endometriosis, psychiatric diseases, HIV, Alzheimers, myocardial infarction, asthma) which he suggests could be partly due to Neu5Gc.
E. Incidentally, the subject of one of his publications stood out to me as being quite different from the others, and a bit more up my alley – “Did Human Reality Denial Breach the Evolutionary Psychological Barrier of Mortality Salience? A Theory that Can Explain Unusual Features of the Origin and Fate of Our Species” – about “our remarkable ability for ignoring or denying reality in the face of clear facts, a high capacity for self-deception and false beliefs, overarching optimism bias, and irrational risk taking behavior (herein collectively called “reality denial”).” link: https://cmm.ucsd.edu/research/labs/varki/_files/publications/b200.pdf