Neu5Gc and Autoimmunity: Hashimoto’s Hypothyroidism

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:

Neu5gc hashis fig 1

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):

Neu5gc hashis fig 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):

Neu5gc hashis fig 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:

  1. An infection in the gut by bacterial pathogens that acquire Neu5Gc from food (primarily beef and pork) and incorporate it into their cell walls.
  2. 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.
  3. 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:

  1. Improving gut barrier integrity and mucosal immunity,
  2. Normalizing or diversifying the gut flora, and
  3. 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.

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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.

 

Leave a comment ?

91 Comments.

  1. 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!!

  2. 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 😥 )!

  3. 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. 🙂

  4. 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.

  5. 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?

  6. 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.

  7. 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.

  8. 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!

  9. 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

    • 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.

  10. Glad to hear ghee is safe! Phew. How about Great Lakes Gelatin?

  11. Interesting article thank you. Do you think bone broth from these animals would still be ok ?

  12. Episode 12: Circadian Rhythms with Paul Jaminet | Phoenix Helix - pingback on February 14, 2015 at 11:21 pm
  13. 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…

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Makes me wonder if this would have any implications for the use of Armour thyroid as it is derived from pigs.

  19. 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/

  20. 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.

  21. 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.

  22. 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.

  23. 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

  24. 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.

  25. 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.

  26. What about that protein powder which is made from beef? I guess that is a no no

  27. Hi Paul !

    What about the use of Armour thyroid ? (since it’s derived from pigs)

  28. 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!

  29. 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?

  30. 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?

  31. 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.

  32. thank you Ben and Paul for your helpful comments.

    😆

  33. 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?

  34. 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…

  35. 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?

  36. 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

  37. 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

  38. 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.

  39. 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.

  40. 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.

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