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 current thinking among researchers who are investigating the therapeutic use of living helminths.

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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]
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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]
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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) [3]
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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) [4]
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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) [5]
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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.) [6]
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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) [7]
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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) [8]
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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) [9]
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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) [10]
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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) [11]

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 two papers provide validation for the practice of self-treatment with helminths.

The problem with clinical trials[edit]

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 other independent lines of evidence that have converged to demonstrate clear and significant health benefits from hosting helminths.

An extensive body of data from epidemiologic studies, clinical observations, and investigations using animal models, has pointed clearly to the idea that humans need exposure to helminths in order to enjoy optimal immune function, [12] 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. [13]

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.

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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. [14]

Trials of pig whipworm ova (TSO)[edit]


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. [15] [16] [17] [18] 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. [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30]

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, which only begin to produce consistent effects after 12 weeks, and, in some cases may produce no indication of benefit whatsoever during the first two years. [31]

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, which was the formulation used in the earlier, more successful trials.

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, and poor subject selection, which is revealed by the high rate of improvement in the placebo group in some cases.

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.

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. [32] 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. 



This glut of poorly designed trials, and consequently flawed meta-analyses, by researchers who clearly had not fully understood the therapy they were investigating, also appears to have dissuaded other researchers from investigating helminthic therapy. This may explain why, after increasing steadily for around 50 years, the annual number of published papers in which “helminthic therapy” is mentioned plateaued from 2014 onwards. (Data from PubMed.)

Trialing the human hookworm (NA)[edit]

TSO is not the only living helminth to have failed to impress when tested using methods 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. [33] 



And socio-medical research has shown that NA is extremely effective as a treatment for MS, with a success rate of approximately 50% for the progressive form of the disease and more than 90% for relapsing-remitting MS. [34]

However, when researchers at Nottingham University carried out a randomized double-blinded placebo-controlled trial in which patients with RRMS were experimentally colonised by hookworms, they concluded that this helminth appeared to be ineffective against RRMS because the particular statistical endpoint determined for the trial had not been reached, [35] even though the data revealed that more than half the patients given hookworms had not developed any new lesions. [36] 



Citizen scientists lead the way[edit]

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 adequately demonstrate the full 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.

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… 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. [37]

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 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, these can usually be obtained instantly, free of charge, from Sci-Hub. Although this pirate domain periodically becomes unavailable from some locations due to legal action by publishers, it invariably resurfaces once its founder, Alexandra Elbakyan, has erected yet another workaround. [38]

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, go to one of the following links and copy/paste the title, or DOI number, of the paper you want into Sci-Hub’s search box. Then hit Return.

https://sci-hub.do
https://sci-hub.st
https://sci-hub.se

In the rare event that the paper you want is not available from Sci-Hub, you will be able to get it free of charge from the Facebook group, Get Your Papers, although this process takes a little longer than using Sci-Hub.

Another good source of full text papers is ResearchGate, which is more likely to have a full text copy than PubMed.

Research papers & articles[edit]

2021[edit]

2020[edit]

  • ✅ 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.” [42] 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.” [43])

2019[edit]

2018[edit]

2017[edit]

2016[edit]

2015[edit]

2014[edit]

2013[edit]

2012[edit]

2011[edit]

2010[edit]

2009[edit]

2008[edit]

2007[edit]

2006[edit]

2005[edit]

2004[edit]

2003[edit]

2002[edit]

2001[edit]

2000[edit]

1999[edit]

1997[edit]

1996[edit]

1995[edit]

1993[edit]

1992[edit]

1991[edit]

1989[edit]

1987[edit]

1985[edit]

1982[edit]

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

1979[edit]

1978[edit]

1976[edit]

  • ✅ 1976 Sept 25 Letter: IgE, parasites, and allergy | PDF This letter reported the first known case of successful helminthic therapy in which colonisation with Necator americanus was shown to resolve hay fever. (NA)
  • ✅ 1976 Aug Serum IgE levels in white and metis communities in Saskatchewan This paper's author suggested that atopic disease is the price paid by some members of the white community of northern Saskatchewan for their relative freedom from helminth infestation and viral and bacterial infection.

1970[edit]

  • 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.

1968[edit]

1932[edit]

Take part in the research[edit]

Socio-medical research at Duke University[edit]

The researchers at Duke have previously reported on data they have already gathered.

The team at Duke are now looking for details about the use of helminthic therapy to treat those conditions for which helminths are less commonly employed, such as lupus, migraine headaches and neuropsychiatric disorders. If you have used helminthic therapy to treat one of these conditions, and whether or not this proved successful, please consider completing the Helminth Self-treatment Survey.

Support the research by donation[edit]

The vast majority of research into the effects of helminths is being carried out by researchers aiming to discover worm-derived molecules that can potentially be used to create drugs, and this work is already well funded by agencies hoping to benefit from the patents and sales which it is anticipated will follow in the wake of successful drug discovery.

Far less well funded is the research into the use and effects of live helminths, and their development for mass application in both the treatment and prevention of autoimmune, inflammatory, metabolic and allergic diseases, including neuropsychiatric conditions.

This latter work is being spearheaded by Prof William Parker and his team at Duke University, the progress of which is dependent on finance being found for each step they take - finance which is hard to secure from the usual sources due to the perceived lack of potential profits.

At the present time, the team at Duke have two main goals for their helminthic therapy research.

  • Writing papers, including reviews, commentaries, and policy briefs about helminthic therapy. In particular, they want to push for change in the landscape of the field to get helminths repositioned away from the modern drug pipeline, which is unsuitable and impractical for helminthic therapy. The Duke team would also like to be able to provide evidence to encourage governments to focus on the ultimate causes of diseases rather than on applying ‘sticking plasters’ to patch up sick people, and to concentrate on disease prevention - especially by means of biota restoration - rather than on the use of expensive pharmaceuticals.
  • Continuing to pursue the traditional pathway, for example, by seeking approval from the FDA for trials with HDCs.

Donations are needed to support this work at Duke, and even small amounts will make a difference. For example, $50 will go a long way towards covering the cost of publishing a scientific paper. $500 will help towards supporting a summer intern working on the HDC project. $5,000 would cover the supply costs of the HDC project for five months. $10,000 could pay for a study in an animal model, for example testing the idea that helminths may help with wound healing. (This is something the team at Duke believe, based on available information, that helminths probably do, but which has not yet been tested. If the hypothesis were shown to be correct, this would provide a huge push forward for the field of wound care.)

Anyone wishing to donate by cheque should make this out either to "Duke University Medical Center", with "for William Parker's HT research" in the memo, or to "William Parker", with "Immunity's Forge" in the memo. The Immunity’s Forge art studio website is also set up to take donations by credit card via a donation page. Either of these approaches will ensure that the money donated will be spent on helminthic therapy research and not on one of the other projects being pursued by Parker’s lab, such as the autism/paracetamol (acetaminophen) project. Both the medical centre and the art studio are registered non-profit organisations, so donations to either are tax deductible for US citizens.

Further reading[edit]

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

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