Helminthic therapy research

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    This page lists almost 900 papers and reports of scientific studies relating to helminthic therapy and closely associated topics such as the Hygiene Hypothesis, the Old Friends' Hypothesis, Evolutionary Mismatch Theory and Biome Depletion Theory / Biota Alteration Theory.

    There are four organisms being used currently in helminthic therapy.

    Some of the reports and papers listed below have focussed on the effects of other species of helminth, or molecules derived from them, but all are nevertheless valuable for the insights they provide about the therapeutic and prophylactic effects of helminths.

    What researchers say about helminthic therapy

    The following quotes illustrate the thinking among researchers who have investigated the therapeutic use of living helminths.

    Although some helminths are known to cause disease and have been labeled parasites, it is now clear that some exposure to this class of organisms is necessary for human health. (Bono-Lunn et al) [1]
    The results strongly support previous indications that helminth therapy can effectively treat a wide range of allergies, autoimmune conditions and neuropsychiatric disorders. (Liu et al) [2]
    What was a costly and sometimes risky venture into the unknown, undertaken by only a few 10 years ago, is rapidly becoming a readily available and well-established resource currently used by thousands of individuals. (Cheng et al, 2015) (PDF)
    Although self-treatment with helminths cannot be recommended by medical professionals due to a lack of blinded, placebo controlled trials, neither should it be discouraged since the available evidence suggests that it is beneficial in most cases when practiced by knowledgeable individuals. (Parker and Morey) [3]
    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) [4]
    Some patients with milder disease or more inclined for natural treatments may consider this as an option. (Prof Constantinescu, Nottingham University, commenting about Multiple Sclerosis.) [5]
    All immunocompetent humans need regular exposure to helminths in order to maintain optimal immune function and avoid risk for inflammation-associated disease… access to helminths is a basic human need. (Smyth et al) [6]
    We need to embrace the view that helminths are a necessary component of the ecosystem of a healthy body, and that helminths should be cultivated for population-wide biota restoration. (Villeneuve et al) [7]
    Biome reconstitution… holds a promise for exposure of all individuals to naturally occurring organisms or selected variants of those organisms in a way that is required for human health. Such exposure must be considered a fundamental human right worthy of government support rather than an option for pharmaceutical development. (Parker and Ollerton) [8]
    In some not too distant futurity, there may come a day when we all take ‘helminth supplements’ along with our Omega 3 fatty acids, vitamins, and whatever else goes to make up a modern balanced diet. (Zaccone et al) [9]
    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) [10]

    Reading packet

    These selected papers provide a good overview of the potential of helminthic therapy and would be suitable resources to include in a reading packet to be given to a doctor or other medical professional, or to someone who is unaware of the evidence and rationale for helminthic therapy. The first three papers provide validation for the practice of self-treatment with helminths.

    Problems with clinical trials using live helminths

    Randomised clinical trials (RCTs) are considered to be the "gold standard" experimental method for researching medical treatments, but the evidence produced by RCTs that have looked at the efficacy of helminthic therapy has been starkly at odds with the many independent lines of evidence that have converged to demonstrate the significant health benefits of hosting helminths.

    An extensive body of data from epidemiologic studies, clinical observations, and investigations using animal models, has pointed very clearly to the idea that humans need exposure to helminths in order to enjoy optimal immune function, [11] and many hundreds of reports by helminthic therapy self-treaters that are featured in this wiki and elsewhere attest to the therapeutic benefits of re-worming. [12]

    So why is there such a chasmic divergence between the results from the majority of RCTs and the evidence from other sources of data? One explanation has been put forward by a team of socio-medical researchers.

    Unfortunately, for a variety of economic, regulatory, and practical issues surrounding the conduct of clinical trials, mainstream 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. [13]

    Trials of pig whipworm ova (TSO)

The first helminth to be systematically investigated by researchers was TSO, the ova of the pig whipworm, Trichuris suis, and results from early trials of TSO carried out in the first few years of the 21st century were very encouraging. [14] [15] [16] But a raft of twelve trials carried out by a different research team between 2008 and 2017, to investigate the effect of TSO in five different diseases, produced such universally lacklustre results that all but three of them were discontinued prematurely. [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28]

    The researchers involved in this unprecedented project made two critical errors in their study design, the first of which was to use a trial length of only 12 weeks. While this is the standard trial period used in pharmaceutical research, it is not appropriate for studies of live helminths such as TSO, which typically only begins to deliver benefits after 8 weeks, and remission only after 20 weeks, with even longer waits experienced by some patients with severe or chronic disease.

    Arguably the most critical mistake was to insist on the use of a novel TSO formulation with a pH of 5.0, even though the investigators were advised against this by the product’s manufacturer, who knew from his own product development work that TSO is most effective when formulated with a pH of 2.4, the formulation used in the earlier, more successful trials. [29] (No abstract | Full text PDF)

    Other significant errors in the design of these trials included the use of a single dose size for all participants, when it is known that the helminth dosage requirements of individuals can vary by as much as a factor of 10. Poor subject selection was also revealed by the high rate of improvement in the placebo group in some trials.

    With so few clinical trials of helminthic therapy having been carried out previously, the sheer number of these “failed” studies overwhelmed the existing helminthic therapy research base to deliver a body blow to the therapy’s reputation that has set back progress by at least 20 years.

    Other researchers began referencing these trials in support of assertions that TSO is ineffective. For example, four of these trials were included in a meta-analysis of six studies which concluded that TSO therapy showed no statistical benefit for IBD patients. [30] Apart from the issues with the product's pH, only one of the trials reviewed in this analysis had lasted for longer than 12 weeks, and the remit of that particular study was only to assess the safety and tolerability (not efficacy) of a single dose of TSO. 

    Trialing the human hookworm (NA)

    TSO is not the only living helminth to have failed to impress when tested using methods that were developed to assess the efficacy of pharmaceutical products.

    In 2007, Correale and Farez had revealed that patients with multiple sclerosis who were hosting a variety of helminths, including hookworms, experienced a reduced number of disease exacerbations compared with patients who were helminth-free. [31] And socio-medical research has shown that NA is extremely effective in the treatment of MS, with a success rate of approximately 50% for the progressive form of the disease and more than 90% for relapsing-remitting MS. (PDF)

    However, when researchers at Nottingham University carried out a randomized double-blinded placebo-controlled trial in which patients with RRMS were experimentally colonised by the hookworm, Necator americanus (NA), they concluded that this helminth appeared to be ineffective against this disease because the particular statistical endpoint determined for the trial had not been reached, [32] even though the data revealed that more than half the patients given NA had not developed any new lesions. [33]

    In order to avoid repeating the design errors made by the teams responsible for previous trials, future studies exploring the therapeutic potential of NA need to take into account the following issues.

    1. For any form of helminthic therapy to be effective, it is essential to maintain continuing exposure to the selected organism. Unfortunately, the period of survival of a helminth varies considerably between individual hosts, and the experience of self-treaters has shown that, in the case of NA, survival of the organism ranges from several years to as little as two months. (See Hookworm lifespan.)
    2. There is more than a 10-fold difference in the level of helminth dosing required to achieve disease remission in different human hosts. Until such time as there are tests capable of providing guidance about the extent of dosing that might be required by each individual, determination of the optimum dosing regimen (the number of larvae in, and the intervals between, each dose) will require the employment by each self-treater of an individualised dose-finding protocol, which can be a lengthy process in the case of NA. (See Long-term dosing is based on individual user experience.)
    3. The benefits derived from hosting NA can take a long time to develop in some cases. While some benefits may appear within weeks, these do not become consistent until at least 12 weeks, and more typically only appear between 3 and 6 months after the initial inoculation. In a few cases, benefits can take up to two years before making their first appearance, and there have even been rare cases in which clear benefits only appeared during the third year. (See Consistent improvement can begin anytime from 3 to 24 months.)
    How the above three factors relate to the therapeutic use of NA is explained in detail on the Hookworm dosing and response page of this wiki.
    4. A further factor that can limit the extent of any therapeutic benefit produced by NA is the potential for certain substances to adversely affect, or even kill, this organism in some individuals. Exactly how it is affected in this way is explained in the Human helminth care manual.
    To take the example of oregano, some NA hosts who ingest this herb may experience reduced benefit from their helminths, possibly even losing their entire colony if they eat a sufficiently large quantity of the plant, consume a concentrated extract or tincture of oregano, or take an oregano oil supplement.
    A more complex situation is found with coconut products, some of which are harmless to NA, while others have been reported to have caused varying levels of harm up to, and including, the total eradication of entire colonies.
    Beyond being dependent on the form in which the substance is encountered, and the dose level, the adverse effect of such substances differs widely between hosts. Users of NA are therefore advised to avoid these, and a few other substances, until they are seeing clear and consistent benefits from the therapy, and then to begin gradually to reintroduce them to assess any effects. This way, the hookworm self-treater is able to learn which, if any, of the potentially risky foods, drugs and other substances they might need to avoid in the long term.
    5. The viability of NA larvae has been shown to decrease rapidly over time from a mean of 85% to < 70% within 14 days. [34] Larval age is therefore another crucial variable that needs to be taken into consideration in future clinical trials, and may perhaps explain some of the inconsistencies in previously reported studies.

    Citizen scientists lead the way

    Unless the scientists conducting trials to investigate the effects of hosting helminths are able to devise methods to assess them as living organisms rather than as pharmaceutical products, and to take into account the unique and dynamic nature of each individual helminth / host relationship, it is likely that clinical trials will continue to fail to reflect the reality regarding the health benefits of re-worming.

    Until this reality is understood, accepted and acted upon by researchers, the best evidence for the benefits of helminth replacement will continue to come from the collated experience of self-treaters.

    … at the present time, systematic data gathering from individuals self-treating may be the most practical and effective means of evaluating the effects of helminth therapy. [35]

    Tips for searching the list of papers and articles

    Symbols used in the list of documents:

    • ✅ - A key paper/report in the development of the therapeutic use of helminths
    • ⚡ - A good place to start if you are new to helminthic therapy, or if you are looking for resources that would help someone else to understand the therapy.

    If you are interested in helminthic therapy in relation to a particular medical condition, use your device’s search function (the 'Command' and 'F' keys on a desktop or laptop, or 'Find in page' in the drop-down menu from the three dots icon on a mobile) to locate the items that are relevant to that disease. Several conditions will require the use of more than one search term, for example:

    • Allergies - search for “allerg”, “atopy” and “anaphylaxis”
    • Anemia - search for “anemia” and “anaemia”
    • Arthritis - search for ”arthrit” and “joint”
    • Asthma - search for “asthma”, “airway” and “wheeze”
    • Autism - search for “autism” and “ASD”
    • Celiac disease - search for “celiac” and “coeliac”
    • Crohn’s disease - search for “Crohn”, “bowel” and “IBD”
    • Diabetes - search for “diabet”, “insulin”, “glucose” and “metabolic”
    • Heart disease - search for “cardio” and “atherosclerosis”
    • Inflammation - search for “inflam”
    • Leaky gut - search for “barrier”
    • Multiple sclerosis - search for “multiple sclerosis” rather than “MS”
    • Obesity - search for “obes” and “adipose”
    • Pregnancy - search for “preg” and “mater”
    • Ulcerative colitis - search for “colitis”, “bowel” and “IBD”

    Obtaining copies of scientific papers

    Unless otherwise stated, the main links presented below are to PubMed abstracts, with additional links being provided to any full text and PDF copies that were available at the time these were added to our list. (Some full text copies are embargoed for a period of time by their publishers.)

    Where full text copies are not available from PubMed, they might be available from ResearchGate, and many papers can also usually be obtained instantly, free of charge, from Sci-Hub. The availability of this pirate domain fluctuates as a result of continuing legal action by publishers, [36] but its founder, Alexandra Elbakyan, constantly provides new site links, the latest of which can usually be found on the Sci-Hub Wikipedia page. (See "URL" in the text box under the black bird.)

    Recently active Sci-Hub links include the following.


    If you find that Sci-Hub is blocked in your area, try accessing it using a virtual private network (VPN). There should always be several countries that allow access to Sci-Hub's website.

    To get a paper from Sci-Hub, copy/paste the title, or preferably the DOI number, of the paper you want into Sci-Hub’s search box. Then hit Return.

    If the paper you want is not yet available from Sci-Hub, you will be able to get it free of charge from the Facebook group, Get Your Papers, or from the Mutual Aid-Science Community.

    Research papers & articles





    • 2021 Dec Treatment of Refractory Chronic Migraine with Worm Eggs: A Therapy Rooted in Evolution (no abstract) | PDF (TSO)


    • ✅ 2020 Jun 15 Hookworm Treatment for Relapsing Multiple Sclerosis: A Randomized Double-Blinded Placebo-Controlled Trial -- Full text (While the primary statistical endpoint of this trial - the cumulative number of new/enlarging T2 and new enhancing T1 lesions at month 9 - was not significantly different between the hookworm group (154) and the placebo group (164), a closer examination of the data reveals that more than half the patients given hookworms did not have any new lesions. “The findings of the research… show that infecting MS patients with a safe dose of… Necator americanus induces immunoregulatory responses and boosts the number of cells which help keep the immune system under control.” [43] The trial’s lead researcher concluded, “I think there would be a niche for this approach - for individuals with mild disease who don't want to take immunomodulating drugs for life and would prefer a more natural approach.” [44])

































    • 1982 Jul Modulation of immune responses by commensal bacteria and intestinal helminth PDF





    • 1970 (winter) The biology of the atopic response Twelve naval officers suffering from hay-fever “for some years” were free from hay-fever for an average of 2 years following colonisation with the large roundworm, Ascaris lumbricoides.




    Further reading

    These pages contain further research papers and articles relevant to each page title.