 eggs from a patient who deliberately infected himself with parasitic worms to treat his ulcerative colitis, an inflammatory bowel disease. The worms may have sent his sent his disease into remission.)
PROPITIOUS PARASITE: Human whipworm (Trichuris trichiura) eggs from a patient who deliberately infected himself with parasitic worms to treat his ulcerative colitis, an inflammatory bowel disease. The worms may have sent his sent his disease into remission.
Image: Kimberley Evason, UCSF
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In 2007, parasite immunologist P'ng Loke sat down for lunch at a University of California, San Francisco, cafeteria with an inquisitive man who had called him earlier that week. Their chosen topic of conversation would deprive many people of an appetite, but the scientist and his guest shared an intellectual hunger for a stomach-churning subject: gut worms—specifically, tiny worm-like parasitic organisms called helminths that live nestled in the gastrointestinal tracts of their hosts.
Loke was fully prepared to answer the man's questions about the parasites he knew so well, but what he did not realize was that his companion had more than just questions—he had worms burrowed in his intestinal walls, worms he had deliberately swallowed. Together, Loke and the worm-wrangler embarked on a research project, the results of which appear today in the December 2010 issue of Science Translational Medicine.
The 35-year-old man who had lunch with Loke was quite healthy in 2007. But only a few years earlier he was in the throes of an inflammatory bowel disease known as ulcerative colitis. An autoimmune disease, ulcerative colitis inflames the colon and leaves it rife with open sores; patients experience intense abdominal pain, vomiting, diarrhea, rectal bleeding and weight loss. While searching for treatments, the man discovered the work of Joel Weinstock, a gastroenterologist, parasitologist and immunologist at Tufts University who has pioneered research on helminthic therapy—treating autoimmune diseases by deliberately infesting patients with parasitic worms, such as whipworm and hookworm.
The results of Loke's new case study—the most recent of only five studies that investigate helminthic therapy in people instead of animals—suggest that helminths may ease the symptoms of autoimmune diseases by increasing mucus production.
"It's a unique study—there's nothing like it before," says Weinstock, who was not involved in the new research. "In this case they had a very unique patient—one who was self-infecting with helminths." Clinical trials on helminthic therapy are particularly difficult to arrange because helminths are live pathogens and have not been officially approved as therapeutic agents by any governmental agency, although the U.S. Food and Drug Administration has granted pig whipworm (Trichuris suis) the status of Investigational New Drug. In contrast to human whipworm (Trichuris trichiura), the porcine variety cannot survive inside the human gut for very long.
"The researchers noticed a specific pattern of behavior, cycling between remission and active disease depending on when the patient infected himself with helminths," Weinstock adds. "This is not a double-blind study, but the pattern is highly suggestive that the worms helped this patient. The major point of this paper is the potential mechanism—mucus production—which has not been looked at properly before."
The Might of Mucus
In the new study, Loke—who is now with New York University—analyzed the man's medical records prior to 2007 and personally tracked the man's health from 2007 onwards. In 2004 the man swallowed a vial of salty liquid brimming with 500 human whipworm eggs, which he obtained from a parasitologist in Thailand. Three months later, he slurped down another 1,000 eggs. The larvae hatched and matured within his gastrointestinal tract, burying their heads in the intestinal wall. By mid-2005, he was virtually symptom free and required no medical treatment for his colitis, except occasional anti-inflammatory drugs to suppress flare-ups. The nearly complete dismissal of colitis symptoms is especially striking because human whipworm infection can itself cause digestive problems, including diarrhea, abdominal pain, nausea, vomiting and, in extreme cases, rectal prolapse. Severe infections can also cause anemia and stunt the growth of children.
In 2008, the number of whipworm eggs in the man's stool began to dwindle, dropping from more than 15,000 per gram to fewer than 7,000 per gram. As the eggs disappeared, the symptoms of colitis returned. So the man infected himself with another 2,000 whipworm eggs and, a few months later, his symptoms practically vanished once again. Repeated colonoscopies revealed that wherever worms colonized his colon, the symptoms of colitis were significantly reduced or nonexistent.
During the 2008 relapse, the researchers found that immune cells in tissues with active colitis produced large quantities of an inflammatory signaling molecule named interluekin-17 (IL-17), but very little IL-22, the latter of which has been linked to wound healing and mucus production. When worms recolonized the colon, however, immune cells began manufacturing much more IL-22. Blood profiling and genetic analysis further revealed that tissues in which helminths thrived increased carbohydrate metabolism—a prerequisite for mucus production.
"Ulcerative colitis is often associated with decreased mucus production and the worms seem to somehow restore mucus production, possibly by inducing a population of immune cells that make IL-22," Loke says. "It's possible the mucus serves as a defensive barrier between bacteria and the gut that prevents bacteria from causing inflammation and crossing over into other tissues." Autoimmune diseases generally occur when the immune system overreacts to benign—and even beneficial—organisms living within the body. In the case of colitis, researchers suspect the reaction is directed toward the bacteria in the gut. Loke thinks that the human body may boost mucus production when it detects helminths as a defense against the parasites; for a patient with ulcerative colitis, the extra mucus may also help calm an excessively aggressive immune system.
"We saw an association with remission and immune cells that make IL-22, but we don't know for sure if these immune cells are actually induced by worms," Loke says. "You can't tell with a sample size of one," which is especially susceptible to the placebo effect. Still, Loke adds, "the results seems quite compelling, especially when you consider the background—all the animal studies and clinical trials that show worms can suppress colitis and other autoimmune disorders."
Mounting Evidence
In fact, in numerous animal studies, helminth infestation has protected rodents against colitis, asthma, rheumatoid arthritis, food allergies and type 1 diabetes.
Researchers have conducted few human studies, but most have shown promise. In a clinical trial published in 2005 in the journal Gut, Weinstock asked 29 participants with Crohn's disease (another autoimmune inflammatory bowel condition) to ingest 2,500 pig whipworm eggs every three weeks for six months. Twenty-three patients (79.3 percent) improved significantly, and 21 (72.4 percent) experienced remission. Both the researchers and participants, however, knew exactly what treatment they were receiving, which makes excluding a placebo effect impossible.
In a controlled clinical trial published in 2005 in Gastroenterology, Weinstock and his colleagues gave 52 participants with colitis 2,500 pig whipworm eggs or a placebo every two weeks for three months. Thirteen of the 29 patients (44.8 percent) who received whipworm eggs improved, compared with only four of the 23 participants (17.4 percent) who received the placebo.
Weinstock and his collaborators point to these trials as experimental evidence that fits a global pattern: immune disorders are much rarer in less developed countries where helminthic infestation is widespread than in industrialized countries where much smaller populations host helminths. The "old friends hypothesis" proposes that the human immune system cannot learn to regulate itself without exposure to common pathogens like helminths that have coevolved with people and that modern hygienic practices deprive people of this necessary exposure, possibly explaining the relatively higher and more recent prevalence of immune diseases in industrialized countries like the U.S.
Loke plans to continue researching helminthic therapy in people and in monkeys. "We are talking about doing a small trial of, say, 10 people and basically doing colonoscopies on them before and after giving them pig whipworm," he says. Loke also mentions that colitis plagues many juvenile monkeys in primate research centers and that he has received a pilot grant to treat diseased monkeys with human whipworm, an as-yet-unpublished experiment that is already returning promising results.
"When I first sat down to lunch with the guy who called me and he started telling me his story, I was really quite skeptical," Loke recalls. "But now I am completely changing my mind about helminthic therapy."
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24 Comments
Add CommentI was also able to achieve remission from Crohn's after getting hookworms and whipworms. You can follow my progress here: http://www.facebook.com/Helminthic.Therapy?v=wall
Reply | Report Abuse | Link to thisAlso, there's a wiki page that contains a ton of information on this topic, including helminthic therapy providers: http://opensourcehelminththerapy.org
A whole lot of research articles on helminthic therapy can be found here: http://goo.gl/CFsY
Fascinating stuff. More evidence that, while vastly improving our lives in other ways, modern society's obsession with sanitation and cleanliness has also been at the root of other problems that seem to be on the rise in industrialized societies.
Reply | Report Abuse | Link to thishttp://evmedreview.com/?p=457 <<-- that article is a very interesting read - it's well written and gives the background on theory of reconstituting a depleted microbiome and how it cures autoimmune diseases.
Reply | Report Abuse | Link to thisHelminthic therapy is an absolutely fascinating therapy, that, if correct, will cause a paradigmatic change in how we view the body's ecology and it's relation to immune system and autoimmunity.
Reply | Report Abuse | Link to thisI have ulcerative colitis, and actually use the very helminths mentioned here to treat it--human whipworm or trichuris trichuria. I have seen excellent results, far beyond what drugs could do for me. I took 1,000 ova 6 months ago and am in complete remission. If you want to know more, you can check out the blog I write to document my experience.
http://coloncomrades.wordpress.com/
I've been using necator americanus (hookworms) to control my Crohn's disease for 3 years now. I find efficacy diminishes when my egg counts decline, like this man in the study, and reinfection provides relief. I have had severe ileal-colonic Crohn's for over 22 years, and failed all standard medications before going into remission on hookworms alone.
Reply | Report Abuse | Link to thisI would like to see much more research in this direction. I tried TSO (trichuris suis ova, or pig whipworms) which are the "legal" safe option. They caused severe diarrhea and abdominal pain. Hookworms have been much more effective for me, but I have to travel to Mexico to get them. The risks of most of our medical choices (cancer, serious infections, surgery) still seem far more dangerous then these nematodes. A medication based on the worm's effects will most likely take decades, and many IBD patients will have lost their colons or parts of their small intestine by then.
I would argue that most IBD patients would be willing to participate in research trials with necator americanus, trichuris trichiura, as well as trichuris suis, and the need for these trials is desperate.
We need much more research into the Old Friends Hypothesis, and helminth therapy in general. We all deserve to lead normal lives, even if it means colonizing ourselves with worms.
To follow my progress over the years, I've kept a blog:
www.waitingforthecure.com
Wondering how you design a placebo for this trial if one of the side effects of whipworm infection is diarrhea and abdominal pain? Not an issue, I guess, with irritable bowel or Crohn's but would be with other autoimmune disorders.
Reply | Report Abuse | Link to thisAlso, what about folks with multiple ailments? I bet it's common for people to have irritable bowel and heart problems at the same time. Yet hookworm can cause heart failure. Doc: "Sorry, the patient died but at least we fixed his GI problems."
It has been shown iron in our foods increases the incidence of Ileitis and Crohn's. So they add iron to our food and it makes us to HAVE to EAT worms ? Somebody needs a beating. ;)
Reply | Report Abuse | Link to this"Depletion of luminal iron alters the gut microbiota and prevents Crohn's disease-like ileitis."
I'm hosting both the hookworm, Necator americanus, and the whipworm, Trichuris trichiura, to treat Crohn's disease and food allergies/intolerance, and the results have been astounding!
Reply | Report Abuse | Link to thisAfter being unable to eat any normal foods at all for many years and forced to live exclusively on a special synthetic medical feed, I am now able to eat normally again. I am also completely free from Crohn's symptoms, environmental allergies (no more rhinitis and sinusitis!) and Restless Leg Syndrome, and the often severe headaches I used to get daily are now infrequent and much less severe, as are the migraines.
Modern medicine had only been able to offer me ineffective palliatives, which invariably caused problems of their own, but these ancient helminths have given me back my health!
You can read my full story at: http://www.foodsmatter.com/allergy_intolerance/food_intolerance/articles/worms_for_food_intolerance.html
Bring on the research! I'm the mom of a three year old who lives on amino acid formula via g-tube because he's allergic to every food he's tried (eosinophilic esophagitis.) I'm chomping at the bit to give helminths a try and am encouraged and hopeful when reading articles like this. Go Dr. Loke! There are many of us out here who are excited about this!
Reply | Report Abuse | Link to thisDr. Loke, if you're reading this, please consider doing research using trichuris trichuria (human whipworm) instead of trich suis (pig whipworm) in your studies.
Reply | Report Abuse | Link to thisI've been watching this research for years, am an active patient, and have spoken with dozens of others who are using helminths. It seems based on the experience of those who have tried them, pig whipworm does not have a consistent or longterm effect.
I know that pig whipworm is 'safer' for study in the sense that they automatically die in 2 weeks inside humans, but the experience of those of us using trichuris trichuria has been that it takes at least 2 months or so for a full effect, particularly as the helminths fully mature around that time.
I have not seen as much success with pig whipworm, based on reading others' experiences. In fact, using that helminth goes against the theoretical basis of the hygiene hypothesis and 'old friends' theory--that these organism down-regulate our immune systems because they evolved to live WITH us. Pig whipworms belong in a pig!
There are now many of us using trichuris trichuria to treat Ulcerative Colitis. Thanks for your research work and keep it up!
I have UC and have benefited from TSO (pig whipworm) and possibly also from human whipworm. TSO coincidentally also knocked out my seasonal hay fever, which used to be pretty strong (red teary eyes and sneezing) for about 6 weeks each early summer but, when I was using TSO, was nonexistent. TSO however never gave me a full UC remission, but it did dampen my UC symptoms by about 30-50%. I needed to take about double the recommended dose, however, even to get that effect. Because of the extreme cost of TSO, and in an effort to get more powerful symptom relief, last year I began trying human whipworm and it did coincide with a remission but then after another medical procedure that required some very powerful antibiotics, I flared up again. One possibility is that, in addition to disturbing my gut, the antibiotics may have killed off most of my whipworms long before they would normally die off... Anyway, I am currently in the midst of repopulating my human whipworms. In my case, the human whipworms, unlike the TSO, do have challenging side effects (diarhea etc) similar to UC - these can last in my case for several weeks, so it's challenging to get through that barrier, to sday the least.
Reply | Report Abuse | Link to thisAnyway, only time will tell how this second try goes- the science is pretty solid with animal studies, but as this article points out, the data on humans is still extremely scanty because the barriers to more widespread use remain so severe. I think it's a tragedy that a natural, essentially probiotics organism was declared a drug- a non-approved drug at that.
Personally, I feel much more comfortable experimenting with something that billions of people (most with no symptoms) have evolved with over millions of years, than some of the IBD drugs that I am also trying (biologics)- with less than stellar success- and which have been around for just ten years or less. Her's hoping these great articles generate a more open, think outside the box perspective among the medical community so that we can refine what is a science still in its infancy.
@Christine Gorman: This is a misunderstanding, easy to clarify.
Reply | Report Abuse | Link to thisThe rare reports of cardiac problems are a result of severe anemia in 3rd world patients with continual, heavy worm exposure, e.g. children with pica (soil eating) due to iron malnutrition, and thus a very high worm infections. Some patients also have co-infections (e.g. one report of bleeding typhoid ulcers) which aren't an issue in the 1st world. In any case, the cardiac problems go away once anemia was treated, so it's not the worms themselves, but the many 3rd world complications that led to severe anemia.
In the dozens of controlled trials and case studies of mild *therapeutic* doses of helminths (either whipworm or hookworm) there have been NO anemia and NO cardiac issues. These modern trials use only a few thousand whipworm eggs, yielding 50-500 whipworm (this is a guess); or a 20-50 hookworm larvae dose). Since these helminths don't multiply in the body, you can control the dose, supplement with iron if needed, (and of course treat any ulcers with antibiotics).
What about this analogy: anemia from ulcers/intestinal bleeding from drugs like aspirin and from NSAID are a known side effect, but that's no reason to ban those and ignore the huge benefit from careful doses of ibuprofen/aspirin. The same goes for mild infections of beneficial helminths that can't multiply inside humans.
I currently carry around 65 hookworms and 200 whipworms. About 3-4 years ago I had a severe autoimmune condition that almost killed me. These helminths put me in essentially complete remission, and, except for all their benefits, if I hadn't been inoculated I wouldn't know I had them. These organisms aren't night-crawlers. They are microscopic when you get them, and would look like hairs if you ever saw them (which you wouldn't). In the past virtually everyone had them. We co-evolved with them, and our immune systems work optimally when we have them. This therapy is being studied at a variety of Universities around the world, and you can go to the Wikipedia article on helminthic therapy to get a general overview of the topic. Here is a forum for people who discuss it: http://health.groups.yahoo.com/group/helminthictherapy/ Here is where you can get it: http://autoimmunetherapies.com/
Reply | Report Abuse | Link to thisHi,
Reply | Report Abuse | Link to thisI'm another person using helminthic therapy to treat asthma and generalised atopy in Australia. My expeeriences with the therapy have been very postive. I now live completely symptom free.
Six months ago, I would spend the first hour of everyday sneezing and needed to treat my asthma with daily medication. I couldn't engage with prolonged physical activity without bronchospasm. Now I have no sneezing and no allergic response to cats!
I have started joggin and recently completed a half-marathon as part of a fundraiser.
Helminthic therapy is a sensible response to a very real public health crisis.
Thanks.
There is a growing pile of research that points to, "we need more research". I have seen no studies that clearly refute the effectiveness of intestinal parasites in managing a range of diseases from hay-fever to Crohns'.
Reply | Report Abuse | Link to thisUnfortunately, parasites are free. They can't be patented & no-one stands to make money from this work. Hence no-one is willing to fund it sufficiently. Someone with a bucket of money, Governments (they stand to save the most through reduced healthcare costs & increased productivity) or a philanthropist need to come to this party...
I have been hosting 35 human hookworms since April 2010, for asthma, rheumatoid arthritis, multiple chemical sensitivity, rhinitis/allergies, & bursitis. My asthma is much improved. Restless leg syndrome (formerly a common response to chemical exposures due to my MCS) is completely gone. The irritability and "brain fog" I used to get after being exposed to chemical fumes is also greatly reduced. Bursitis may be a bit better, but it's hard to tell. My rhinitis (nasal allergies) is only slightly improved, but I just re-inoculated with 35 more larvae, and I'm hoping this higher dose will help. My "atopic dermatitis" (a rash I get after chemical exposures) is also considerably improved. I've lived with MCS since 1986 and helminthic therapy is THE most effective therapy I've tried (and I have tried a LOT). Note to those who are scared off by claims that helminths can be harmful: the main threat to health is from anemia from heavy infections with many hundreds or thousands of worms. There are no known risks at the doses prescribed therapeutically, and they CANNOT reproduce inside the body, nor can they be accidentally spread to others in countries with plumbing: hookworms and whipworms both live part of their life cycles in the soil, and so cannot be spread directly to another person. (I have no idea why that earlier person said they are a risk to the heart. I believe she is wildly misinformed. I have been reading scientific literature about them for over a year and have heard no mention of that.) After 25 years of chronic suffering, hookworms are giving me my health back. For those of you with auto-immune or inflammatory illnesses, who are waiting for science to create drugs from these precious little critters, think about taking your health into your own hands. The therapy is out there now--you don't have to wait. And the only side effect I suffered was transient flatulence for a few weeks--a small price to pay for so many positive health effects!
Reply | Report Abuse | Link to thisMy wife is at the moment following helminthic therapy with hookworms to treat her allergies,food intolerances,rosacea and general immune system imbalance. It is still early days,but,after following for several months the comments posted in the yahoo group that deals with helminthic therapy by fellow sufferers and their results with said therapy,we are confident that the time will arrive when we will equally be able to claim success with it. If you want to learn about it,I would recomend to join the group and start reading . Good luck.Alberto PS In the last 14 years we have try many other treatments to cure the problems,obviously without definitive results . A.
Reply | Report Abuse | Link to thisI self-inoculated during late September with 35 hookworms to help with my asthma. Although only 9 weeks has passed, the sensitivity of my bronchial tubes has decreased significantly. I am hoping for the return of normal sensitivity in the coming weeks. This is incredible!!!! Helminths offer a solution that traditional medicine cannot.
Reply | Report Abuse | Link to thisAs a product of decades of sanitation and cleanliness training I find the idea of little wormy microbes very disturbing. Since most research shows the need to re-infect I wonder if perhaps a more permanent fix may be to alter mucous production cells to produce the needed substances automatically without the need of parasites. I also wonder if, since I don't have these symptoms, I already have these creepy little critters in me. I find that thought rather nasty. Bacteria are one thing, worms are another entirely.
Reply | Report Abuse | Link to thisI saw this in House MD! About 1 year ago the episode "Teamwork" Season 6 episode 7.
Reply | Report Abuse | Link to thisMikeLuis225, I'm an ulcerative colitis patient, where do you purchase helminths from? I've seen a lot of posts about this but none pointing to where they can be purchased from?
Reply | Report Abuse | Link to thisRegards,
Sue
Does anyone know where helmiths can be purchased from, I've heard they are not available in the US?
Reply | Report Abuse | Link to thisMy son has been diagnosed with Crohns Disease and I'm wondering if someone can tell me how he can become part of this worm trial, if it's still ongoing somewhere. Thanks!
Reply | Report Abuse | Link to thisHi - you can try searching for clinical trials involving helminths here http://www.clinicaltrials.gov/ct2/results?term=helminth&Search=Search or you can get in touch with P'ng Loke and see if he knows of any ongoing trials http://www.med.nyu.edu/biosketch/lokep01
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