Hookworm Infection No Magic Bullet for Gluten Tolerance in Celiac Disease

I'm the hookworm host that was featured in the previous article. At this point I'm tempted to shoot a video of me eating spaghetti followed by an apple pie dessert.

In our Helminthic Therapy Support Group I think few people hosting hookworms would say that their hookworms last 42 weeks. The one time I let mine die out it was at 30-week mark. I know that because I saw the white worm corpses in my stool, and I then got sick and had to go back to being gluten-free and meat-free shortly thereafter, so I would have flunked out of that study. Many of us re-inoculate at the 12-week mark. I find 26 weeks, twice a year, works for me. It varies for everybody because it depends on how quickly the immune system kills the hookworms off. Those with GI immune issues like IBD (celiac, ulcerative colitis and Crohn's) tend to kill their hookworms off faster. Also, nobody uses the protocol that was used in the study. People usually start with 5 larvae and work up slowly depending on the results that they see. Some need relatively few hookworms to get relief. Others might need 10x as many.

In the study nearly 1 in 4 people didn't maintain a hookworm colony. Was one ever established for these subjects? Or did the hookworms die off mid-study? Perhaps an insufficient number of hookworms were alive to make much difference to their gluten sensitivity.

So far as I've learned people who host hookworms fall into 3 camps in regard to their tolerance for gluten. For one group, hookworms don't help at all, at least not for gluten. A second group has a changed (diminished) response to gluten exposure. Basically these people need to stay on a gluten-free diet but they won't have to take off work anymore from casual gluten exposures. And then there's my group, people who could bathe in gluten for all the difference it would make. We become normal and can eat as we like. For that group, hookworms are life-changing. I wish I had the numbers for the relative sizes of the groups but unfortunately I don't.

I maintain that hookworms are worth trying. In low numbers they are benign, and since people with celiac disease often have other immune related conditions like I did, there's the opportunity for the hookworms to help there as well.

There's also the matter if I had taken those iffy study results seriously I wouldn't be where I am today. And no, I don't usually work on my PC surrounded by baked goods. But I could if I wanted to.

The conclusion by the authors of the study featured above - Croese et al, 2020 (1) - that infection with NA does not obviate the need for a gluten-free diet is rendered unreliable by methodological deficiencies in the trial design.

The trial participants each received two doses of either 10x or 20x N. americanus (NA) hookworm larvae at weeks 0 and 8, and were challenged with gluten between weeks 12 and 42, with an optional 52 week extension for those participants without celiac disease symptoms. However…

* The trial period was of insufficient length. While some of the benefits derived from hosting NA may begin to appear within a few weeks, they do not become consistent until at least 12 weeks, and, in some cases, can take up to 2 years to fully develop. (2)

* Some participants may have received an inadequate number of NA. The level of helminth dosing required to achieve disease remission in different hosts can vary by a factor of 10. (3)

* Dosing with NA may not have been continued for long enough to maintain efficacy. While NA have been reported to survive in hosts for many years, data gathered from the community of thousands of helminth self-treaters show that, in practice, NA may survive for as little as 2-3 months in some individuals, especially those with digestive diseases. (2)

* The worms hosted by some trial participants may have lost efficacy before the end of the trial, due to the possible ingestion of certain dietary substances that can adversely affect, or even kill, NA in some individuals. (4)

A more recent study, by Venkatakrishnan et al (3), has highlighted the fact that some “gold standard” helminthic therapy trials, have, in spite of their double-blind, placebo-controlled design, provided lacklustre or even false negative results due to a lack of adequate consideration of the biology of living helminths and their interactions with their hosts - exactly the points I have made immediately above.

For more about these issues, see: Problems with clinical trials using live helminths: Trialing the human hookworm (NA). (5)

(1) Randomized, Placebo Controlled Trial of Experimental Hookworm Infection for Improving Gluten Tolerance in Celiac Disease

(2) Hookworm dosing and response

(3) Socio-medical studies of individuals self-treating with helminths provide insight into clinical trial design for assessing helminth therapy

(4) Human helminth care manual

(5) Helminthic therapy research: Problems with clinical trials using live helminths

Based on this peer reviewed study, Celiac.com does not, at this point, recommend that anyone with celiac disease forgo the only safe and effective treatment for celiac disease, which is a gluten-free diet.

@dixonpete and @John Scott, please produce a list of recognized celiac disease experts who support hookworm infection for celiac disease instead of the gluten-free diet.

On 1/16/2023 at 11:25 AM, Scott Adams said:

Based on this peer reviewed study, Celiac.com does not, at this point, recommend that anyone with celiac disease forgo the only safe and effective treatment for celiac disease, which is a gluten-free diet.

@dixonpete and @John Scott, please produce a list of recognized celiac disease experts who support hookworm infection for celiac disease instead of the gluten-free diet.

I am not recommending that the hosting of helminths should replace a gluten-free diet. My post, above, was only intended to draw attention to the fact that the conclusions of Croese et al cannot be relied upon, leaving the question as to how effective hookworms might be in addressing celiac disease still open.

It is, of course, eminently sensible for you to recommend that anyone with celiac disease does not forgo a gluten-free diet, but this advice does not preclude celiacs from also hosting helminths, which current scientific understanding of the immune system’s development and function indicates is likely to be beneficial.

https://helminthictherapywiki.org/wiki/images/2/2b/A_prescription_for_clinical_immunology-_the_pills_are_available_and_ready_for_testing._A_review.pdf  (PDF) 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1618732/ 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2632706/ 

Socio-medical studies indicate that self-treatment with helminths is effective for many people, probably even most people, in terms of alleviating inflammatory-related diseases.

http://www.yourwildlife.org/wp-content/uploads/2015/05/galley-proof-v2.pdf  (PDF) 

https://pubmed.ncbi.nlm.nih.gov/27240605/ 

https://helminthictherapywiki.org/wiki/images/a/ad/Socio-medical_studies_of_individuals_self-treating_with_helminths_provide_insight_into_clinical_trial_design_for_assessing_helminth_therapy.pdf  (PDF) 

It is therefore likely that someone with celiac disease will enjoy generally improved health while hosting benign, mutualistic helminths. It is up to them, if, once their health has improved, they then want to test their tolerance of gluten, in the way that @dixonpete has done.

Obviously, if they do this, they should get the appropriate tests to ensure that any consumption of gluten in the wake of an overt increase in tolerance does not cause a hidden resumption of the disease process that had previously been halted by a gluten-free diet.

10 hours ago, Scott Adams said:

@dixonpete and @John Scott, please produce a list of recognized celiac disease experts who support hookworm infection for celiac disease instead of the gluten-free diet.

Nobody is making the claim that hosting hookworms will resolve every celiac's disease. Unfortunately it just doesn't work that way. What does seem to happen is that for the majority of subjects in most all the studies is that reactions to gluten are lessened. John Scott makes a good case that using best practices gained from real world experience hosting would yield better results than seen in the studies.

Hookworms for many would mean less risk of the extreme gluten reactions to casual exposure. Scanning the forums for food sensitivity/food sensitivities I can see it's a constant refrain on this site. That's one of the things hosting hookworms is known best for resolving.

I go back to my example. My celiac disease got fixed. As did my colitis, all because of hosting. If I stop hosting I regress back to the way I was. That's called proof of concept and proof of mechanism. Probably there is some genetic explanation why hosting works better for some than others. Till that's known it's a lottery. You buy your ticket, and you might win, and you might lose. But unless you play there's no possibility of success.

You asked about experts. John Scott heads up the world's biggest support group for helping people do helminths like hookworms. There is no one with more practical experience on the topic than him. I did write to Dr Mark Davis, the person who did that video I showed you claiming he's had success treating celiacs with hookworms. Hopefully he'll chime in.

I see nothing wrong with the study, and I do not buy the criticisms of the study that you've linked to (some self promotional links have been removed). Again, the multiple PhD's involved in the study spent years creating, conducting, and then publishing their very well-designed double blind study--with zero financial interests involved. 

I cannot conclude that those pushing for hookworm treatment here do not have a financial interest in that, but I can say they neither are qualified to make the claim that this study's conclusions are incorrect. On one hand both of you are saying that the study is flawed, and on the other hand you are both agreeing with its conclusion--that celiacs should not eat gluten. Well, which is it?

38 minutes ago, Scott Adams said:

I see nothing wrong with the study, and I do not buy the criticisms of the study that you've linked to (some self promotional links have been removed). Again, the multiple PhD's involved in the study spent years creating, conducting, and then publishing their very well-designed double blind study--with zero financial interests involved. 

I cannot conclude that those pushing for hookworm treatment here do not have a financial interest in that, but I can say they neither are qualified to make the claim that this study's conclusions are incorrect. On one hand both of you are saying that the study is flawed, and on the other hand you are both agreeing with its conclusion--that celiacs should not eat gluten. Well, which is it?

I can't speak for John, but the only money I've seen has gone out to purchase hookworm larvae. My motivation is humanitarian. I think back at how sick I was, and I look around and see others who are currently in the same boat that I was, and I want to give them a good shake and get them out of that hole. Do you have any idea how much good karma you get from acts like that if they do get better? Obviously you do, because in a similar way you run a site dedicated to helping people. To my eyes, promoting the adoption of hookworm hosting is the same thing.

Back in 2018 after my first inoculation with hookworms I got back on gluten as soon as I could and stuffed myself with it. I didn't have antibody tests and I didn't get a biopsy done. Those were mistakes committed from ignorance. But it turned out I was lucky and got away with it.

As I said before, if celiacs host hookworms, one of three things will happen. The first is nothing. Failure, at least in regard to gluten. No improvement. The second possible outcome is a lessened reaction. No more norovirus-like events. Perhaps instead it's just an upset stomach to a gluten exposure. The third possibility is what I got. Cake. Whenever I want it. The good stuff. And not just that, I got back all the other foods I couldn't eat. Previously I was down to 12 foods and still felt poorly and was going to the bathroom 6x a day. Now I feel fine and go 1-2x a day. It's a night and day improvement in quality of life and I have the ability to go to any restaurant I like and eat anything off their menu.

But as I have said, you won't know how things will go until you try.

John's entire focus is helping people successfully get started with hosting helminths. It's not an exaggeration to say he knows more than those PhDs as he's the center of a whole community of thousands of people actively using them and trying to find the best way to navigate their various health conditions. He might be too modest to say that but I'll say it for him.

As for me, I feel justified saying hosting hookworms can help celiacs because they helped me. I was an uber-reactive celiac at risk of losing my colon to colitis and now I'm healthy and have a fridge and freezer full of bread. So damn right I disagree with those studies.

On 1/17/2023 at 11:52 AM, Scott Adams said:

I see nothing wrong with the study, and I do not buy the criticisms of the study that you've linked to (some self promotional links have been removed). Again, the multiple PhD's involved in the study spent years creating, conducting, and then publishing their very well-designed double blind study--with zero financial interests involved. 

I cannot conclude that those pushing for hookworm treatment here do not have a financial interest in that, but I can say they neither are qualified to make the claim that this study's conclusions are incorrect. On one hand both of you are saying that the study is flawed, and on the other hand you are both agreeing with its conclusion--that celiacs should not eat gluten. Well, which is it?

Last year, Venkatakrishnan et al, published a study with the following conclusion.

"Unfortunately, for a variety of economic, regulatory, and practical issues surrounding the conduct of clinical trials, main stream trials have thus far been unable to accommodate the nuances of helminth therapy. Foremost among the issues that clinical trials must address before they can effectively test the potential for helminth therapy are (a) details in formulation of the helminth product that affect efficacy, and (b) the very wide range of doses typically needed within a cohort of individuals."

This paper’s supervising author is a professor of medicine, an immunologist who ran one of the world’s largest transplant laboratories. So I’m in very good company when I draw attention to the methodological deficiencies of studies like the one reported by Croese et al in 2020.

To reiterate my position, since the Croese et al study design was flawed, the question as to how effective hookworms might be in addressing celiac disease is still not fully answered. Until such time as a better designed study is mounted, it is unquestionably advisable for anyone with celiac disease to continue to eat a gluten-free diet, but this advice does not preclude celiacs from also hosting helminths, which current scientific understanding of the immune system’s development and function indicates is likely to be beneficial to their health. I would expect that in many cases where celiacs become helminth hosts, they will likely find that they are at least spared severe reactions to accidental gluten exposures. Some may experience additional benefits.

As for my personal interests, they are most definitely not financial. I first began my involvement in the global helminthic therapy movement a decade ago, after I retired, and have worked tirelessly since then, without remuneration of any kind, to gather and curate data about the therapy with the sole intention of making this knowledge as widely available as possible, for free, to enable more people to benefit from what is a truly remarkable therapy with a solid evidence base. 

"Twenty years from now everybody is going to have a helminth, and no insurance company will begin to cover you if you don’t have your helminths. We’re very confident in the science, that every single human being needs a helminth. It’s part of our biology." (Prof William Parker, Duke University, 2016.)

"In developed countries, where we are well nourished, worms are potentially good. If I had Crohn’s disease, ulcerative colitis or multiple sclerosis, I would infect myself without hesitation." (Prof Alex Loukas, Australian Institute of Tropical Health & Medicine.)

Also, check out this graphic, prepared by Robert Summers, Professor Emeritus, Department of Internal Medicine at the University of Iowa, to illustrate the relationship between an absence of helminths and higher rates of autoimmune disorders - a category that includes celiac disease.
Distribution of Autoimmune Disorders and Helminths.

So it seems that your position, even though you disagree with this study's methods, is the same as the authors of this study--I just want to be clear here.

It seems that you agree that people with celiac disease and do hookworm therapy should not eat gluten, and that hookworm therapy may only be helpful for low amounts of gluten, for example cross-contamination that celiacs might encounter when eating out, going to other people's houses, etc.--this is exactly what this study concludes.

I will point out that AN-PEP enzymes are a far better choice for this purpose, as AN-PEP been shown in numerous studies to break down small amounts of gluten in the stomach, before it reaches the intestines, thus avoiding the cascading autoimmune reaction. One brand, who is a sponsor here (but not why I'm sharing this), is GliadinX, and for anyone interested in reading through the many studies the links are on their site: https://www.gliadinx.com/publications 

Given a choice between hookworm therapy or AN-PEP enzymes, it is clear to me that the enzymes should be the first choice.

1 hour ago, Scott Adams said:

Given a choice between hookworm therapy or AN-PEP enzymes, it is clear to me that the enzymes should be the first choice.

I completely disagree. Again, I'm drawing from personal experience here, but my GI tract under hookworms has changed from a nightmare to deal with to being a veritable ticking clock. It seems no matter I throw at it, it just keeps chugging along. Completely aside from gluten I regularly find foods like I did yesterday, ham and pea soup, that I had long given up on as being too troublesome, that are now totally fine.

Enzymes don't compensate for a broad based immune system dysfunction.

Also, it's not clear to me what you think the downsides are of HT. Aside from the initial rash, I've never had any awareness of the hookworms' presence. I can eat anything, and I'm not daily popping enzyme capsules in the hope of being crushed by a quarter of a crouton, or however much gluten enzymes can reasonably expect to be able to handle.

Re-reading this before posting, I acknowledge the benefits I get from hookworms appear to be on the high side of what can be expected. That said, wouldn't it be just sensible to find out how you would be on them?

2 hours ago, Scott Adams said:

So it seems that your position, even though you disagree with this study's methods, is the same as the authors of this study--I just want to be clear here.

It seems that you agree that people with celiac disease and do hookworm therapy should not eat gluten, and that hookworm therapy may only be helpful for low amounts of gluten, for example cross-contamination that celiacs might encounter when eating out, going to other people's houses, etc.--this is exactly what this study concludes.

I will point out that AN-PEP enzymes are a far better choice for this purpose, as AN-PEP been shown in numerous studies to break down small amounts of gluten in the stomach, before it reaches the intestines, thus avoiding the cascading autoimmune reaction. One brand, who is a sponsor here (but not why I'm sharing this), is GliadinX, and for anyone interested in reading through the many studies the links are on their site: https://www.gliadinx.com/publications 

Given a choice between hookworm therapy or AN-PEP enzymes, it is clear to me that the enzymes should be the first choice.

OK, to be clear, my position is not quite the same as that of Croese et al.

Rather than stating, as they have done, that "Hookworm infection does not restore tolerance to sustained moderate consumption of gluten…" , more careful researchers would have said that, "In our study, hookworm infection did not restore tolerance to sustained moderate consumption of gluten…" which is a rather different conclusion.

Due to its apparent methodological flaws, this research can’t be taken as the last word on the potential benefit for celiacs of hosting hookworms, and it’s to this fact that I wish to draw attention. I don’t want people to write off helminthic therapy based on this trial, especially as there are numerous celiacs in the helminthic therapy self-treatment community who have reported significant benefits.
Helminthic therapy personal stories: celiac disease

Granted, these are anecdotal accounts, but when there are a number of people reporting similar effects, there is reason to look more closely at what they are doing. And one team of researchers said last year that, "At the present time, we would argue that the primary “lab” for helminth therapy seems to be within the community of self-treaters. This “biohacking” phenomena of science outside of the established main stream is not unique to helminth therapy. However, given that helminth therapy addresses a fundamental cause of disease in Western society, this particular biohacking endeavor may in fact be critical for public health."
https://www.sciencedirect.com/science/article/pii/S1383576921002063?via%3Dihub 

As you say, Aspergillus niger‐derived prolyl endoprotease (AN‐PEP) appears to be a very promising agent for degrading gluten in the stomach. However, the authors of the most recent randomised clinical trial that I was able to access on PubMed (König et al 2017) concluded that, while the AN-PEP enzyme appears to be effective as a digestive aid to protect against the unintentional intake of gluten, it is not intended to replace a gluten-free diet in gluten-related disorders.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638938/ 

Unlike an enzyme product, helminths, such as hookworms, deliver powerful immune modulation with far-reaching health benefits generally, in addition to the possibility of protection against at least accidental gluten exposure. And you don't need to remember to take helminths with you when you eat out because they are always with you, as long as you re-dose every few months.

Since a majority of those with celiac disease recover fully on a gluten-free diet alone, clearly hookworm infection would not be necessary no matter what. For those who are recovered, like myself, and who still want to eat in restaurants or outside their homes, AN-PEP enzymes have worked quite well, and it is no trouble at all to take a couple of capsules with a meal. 

The very criticisms you have of this study--that apparently a large number of PhD's can't figure out how to use hookworms effectively, is in fact STRONG evidence that the vast majority of celiacs SHOULT NOT be trying to use them for this purpose.

The only people with celiac disease who might want to try hookworm infection for treatment would be those with refractory spue, which can be deadly, and is a runaway autoimmune process that may not be associated with gluten contamination (but often is and can be reversed by dietary changes if this is the case).