Helminthic therapy and diabetes

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NB. This page is concerned with the metabolic disorders commonly known as diabetes mellitus, which should not be confused with diabetes insipidus.

Type 1 and Type 2 diabetes are major health issues across the globe. There is evidence that helminthic therapy may assist with prevention and treatment of these disorders.

Type 1 diabetes

Helminths and type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disorder in which the immune system attacks and destroys insulin-producing beta cells in the pancreas. Once these cells are destroyed, the body is unable to produce insulin, which regulates blood glucose levels. A World Health Organization study found a significant difference in prevalence around the world:

A greater than 350-fold difference in the incidence of T1D among the 100 populations worldwide was reported with age-adjusted incidences ranging from a low of 0.1/100,000 per year in China and Venezuela to a high of 36.5/100,000 in Finland and 36.8/100,000 per year in Sardinia. The lowest incidence (<1/100,000 per year) was reported in the populations from China and South America and the highest incidence (>20/100,000 per year) was reported in Sardinia, Finland, Sweden, Norway, Portugal, the UK, Canada, and New Zealand. [1]

A 25-year study found that the rate of type 1 diabetes in Europe is increasing by more than 3 percent per year [2], and a recent study by the US Centers for Disease control found increasing rates of both type 1 and type 2 diabetes in young US citizens. [3] The World Health Organization has found that diabetes is becoming more prevalent in middle- and low-income countries. [4]

Many have hypothesized that the differential rates, as well as the current increase in middle- and low-income countries, may be related to industrialization and the medical and hygienic practices that come with it. [5]

Prevention and treatment of T1D

Abundant evidence indicates that helminths and their by-products can exert immunomodulatory effects that prevent or delay the onset of T1D.… In the future, helminth-derived supplements may be included as part of a modern balanced diet. [6]

There is evidence in both human and animal models that helminth infection is protective against the development of T1D. [7]. A study found that helminth infection "disrupt[s] the pathways leading to the Th1-mediated destruction of insulin-producing beta cells." [8] Findings like these have led some researchers to call for further study of helminth therapy as a deliberate preventative measure against the development of T1D. [9]

Treatment is more complicated. Once the symptoms of this disease develop, the majority of insulin-producing beta cells have been lost. But there is cause for hope, as multiple approaches to regenerating these cells are being studied. It is now clear that, at least in mice, the pancreas contains cells capable of being converted into insulin-producing beta cells. This can be done at any age and the cells can be regenerated several times. [10] Encouragingly, another study found that a drug could encourage the generation of new insulin-producing beta cells in the human pancreas as well. [11] Stem cells are another promising subject of research on regenerating insulin-producing beta cells. [12] With the possibility of creating new beta cells, the combination of this regeneration with helminthic therapy to prevent further autoimmune destruction of beta cells may turn out to be a viable long-term treatment for Type 1 diabetes.

There is also some evidence, however, that beta cells can be regenerated through immunomodulation alone.

New research shows promising progress in the use of anti-inflammatory cytokine for treatment of type 1 diabetes. The study reveals that administration of interleukin-35 (a protein made by immune cells) to mice with type 1 diabetes, reverses or cures the disease by maintaining a normal blood glucose level and the immune tolerance. [13]

Another study found that increasing protective T-regulatory cells in the lymph nodes (the 'gates' of the pancreas) may help restore the production of insulin in T1D patients. [14] Helminths are capable of normalizing T-regs, but we don't yet have research that specifically confirms the regeneration of pancreatic beta cells through T-reg modulation via helminth infection.

Research on mechanisms of prevention and treatment

Animal models, while not a perfect way to study human health, allow us to understand the interaction of helminth immunomodulation and T1D on a detailed level. [15] [16]

In this study we show that soluble extracts of S. mansoni worm or egg completely prevent onset of type 1 diabetes in these mice but only if injection is started at 4 weeks of age... These effects of schistosome antigens on the innate immune system provide a mechanism for their ability to prevent type 1 diabetes in NOD mice. [17]

T cells from H. polygyrus (Hp)-inoculated NOD IL-4(-/-) mice to NOD mice blocked the onset of T1D. [18]

A significantly lower percentage of T. crassiceps-infected mice (40%) developed T1D compared to the uninfected group (100%). Insulitis was remarkably absent in T. crassiceps-infected mice, which had normal pancreatic insulin content, whereas uninfected mice showed a dramatic reduction in pancreatic insulin. [19]

Some studies have also found that helminths may help, even after the onset of T1D.

• One mouse model study found that helminth infection "significantly inhibits T1D... and also reduces the severity of T1D when administered late after the onset of insulitis." [20]

• Experimentally induced type 1 diabetes is suppressed in mice during infection by the helminth, Heligmosomoides polygyrus. This is achieved by the secretion of trehalose which induces production of suppressive CD8+ Treg cells by means of alteration to the intestinal microbiota. [21]

Recent Research

• 2023 Jul 26 How do parasitic worms prevent diabetes? An exploration of their influence on macrophage and β-cell crosstalk -- Full text | PDF

By regulating the activities of islet macrophages and β-cells (and other endocrine cells), helminth parasites shape their crosstalk. This offers a unique opportunity to exploit helminths’ mechanisms for survival in their mammalian hosts to establish an environment that preserves β-cell mass and function and thus offers the potential as a cure for both T1D and T2D.

Personal experiences

See Helminthic therapy personal stories: Diabetes type 1.

Type 2 diabetes

Helminths and type 2 diabetes

Type 2 diabetes (T2D) is a condition in which the body still produces insulin, but develops insulin resistance and cannot use it effectively. The pancreas will try to compensate by producing more insulin, leading to glucose accumulation in the bloodstream. T2D can lead to health complications such as kidney problems, vision problems, nerve damage, poor blood circulation, heart attack, stroke, erectile dysfunction, and slow wound healing. Risk factors for T2D are mainly age, obesity, family history, and physical inactivity, but there is significant geographical variation in prevalence that points to additional risk factors:

As in type 1 diabetes, there is marked geographical variation, but the pattern is different. The prevalence is lowest in rural areas of developing countries, generally intermediate in developed countries, and highest in certain ethnic groups, particularly those that have adopted Western lifestyle patterns... It is likely that interactions between the environment/lifestyle and genetic factors provide the explanation for the risk of type 2 diabetes. [22]

Some explanation of this geographic variation may relate to rates of helminth infection, which a number of studies around the globe have shown to be protective against the development of T2D. [23] [24] [25] [26] [27] Some of these studies found that the removal of helminths from an individual appears to increase their risk of insulin resistance and T2D. This could be an important, but overlooked, contributor to the higher prevalence of T2D in industrialized nations, where helminth infections are much lower. [28] [29]

Some...antiparasitic drugs might induce diabetes, whereas helminth infections appear to afford some protection against future diabetes. [30]

Helminth infections... may be protective against the development of diabetes, and this finding opens up new territory for discovery of novel therapeutics for the prevention and treatment of diabetes.[31]

Participants with previous schistosome infection had... a lower prevalence of diabetes and metabolic syndrome compared with the uninfected, contemporaneous controls. [32]

We found previous schistosome infection (PSI) significantly correlated with lower prevalences of metabolic syndrome and its components, including central obesity, hypertriglyceridemia and low high-density lipoprotein cholesterol, which indicates that the potential long-term effects of PSI may reduce the risk of metabolic syndrome. [33]

Low fasting blood sugar and reduced prevalence of dyslipidemia in S. mansoni egg positive participants might suggest inverse association of S. mansoni infection and development of metabolic syndromes. [34]

Thus helminth infections alleviate and anthelmintic therapy partially restores the plasma cytokine and chemokine levels in helminth-diabetes co-morbidity. Our data therefore offer a plausible biological mechanism for the protective effect of helminth infections against T2DM. [35]

In this paper, we provide a comprehensive review of intestinal helminths' protective effects against T2D. [36]

A proof-of-concept human clinical trial is currently underway on the safety and usefulness of the human hookworm for patients with metabolic syndrome. [37]

Type 2 diabetes and the immune system

It is becoming more apparent that the immune system is involved in T2D, as researchers find that experimental immunomodulation has an effect on this condition [38] Helminths are known immunomodulators, and there is evidence that they affect the immune system in a way that can help T2D [39] [40] [41] [42]

Helminth-induced type 2 cytokines increase the number of regulatory T cells and alternatively activated macrophages, resulting in modulation of the host-immune system. Studies on these parasite-induced immunoregulatory mechanisms might contribute to the development of new therapies for inflammatory diseases, including type 2 diabetes. [43]

Helminths and certain protozoan parasites are able to manipulate the host immune response towards a TH2 immune phenotype that is beneficial for their survival, and there is emerging data that there is an inverse correlation between the incidence of MetS (metabolic syndrome) and helminth infections, suggesting that, as with autoimmune and allergic diseases, helminths may play a protective role against MetS disease. [44]

There is also growing evidence to suggest that type 2 diabetes involves inflammation, [45] [46] and inflammation may be the reason why high blood sugar levels damage blood vessels in people with diabetes. [47] It’s been known for more than a decade that helminths are effective against inflammation [48] [49] [50] [51] [52]. A 2017 study found that:

...helminth infections... can modulate IR is by inducing a chronic, nonspecific, low-grade, immune suppression mediated by modified T-helper 2 (Th2) response (induction of both Th2 and regulatory T cells) which can in turn suppress the proinflammatory responses and promote insulin sensitivity. [53]

Research on mechanisms of prevention and treatment

Controlled studies on animal models have helped scientists understand how helminth infection can prevent T2D through immunomodulation, gut biome alteration, fatty acid metabolism, and other mechanisms. [54] [55] [56] [57] [58] [59] [60] [61]

Parasitic nematode infection has both preventive and therapeutic effects against the development of obesity and associated features of metabolic dysfunction in mice. [62]

Recent studies in mice describe how type 2 immune cells, traditionally associated with helminth infection, maintain adipose tissue homeostasis and promote adipose tissue beiging, protecting against obesity and metabolic dysfunction. [63]

Studies on whether helminths may be an effective treatment, as well as an effective preventative measure, have also shown promise.

...nematode infection appears to provide an effective option for the treatment of T2D by improving inflammatory status through restoration of the cytokine imbalance, inhibition of glucose absorption from the small intestine and decline of excess fat accumulation in the liver. [64]

We demonstrate a beneficial effect of helminth infection on the systemic inflammatory milieu, intestinal dysbiosis and metabolic endotoxemia, that is highly characteristic of T2DM. [65]

The present study suggests that experimental infection with low hookworm doses is safe and is associated with improvements in glucose homoeostasis in people with Metabolic Syndrome and at risk of type 2 diabetes mellitus. [66]

Research in humans

• 2023 Aug 29 Hookworm infection induces glycometabolic modulation in South Indian individuals with type 2 diabetes -- Full text | PDF

In summary, our study reveals that hookworm infestation may confer protection against the pathology associated with T2DM by alleviating the altered levels of glucose indices, pancreatic hormones, incretins, and adipocytokines… Furthermore, our results highlight the potential of worms as a new therapeutic strategy to conquer T2DM by regulating host immunity.

• 2023 Jul 26 Effect of experimental hookworm infection on insulin resistance in people at risk of type 2 diabetes -- Full text | PDF

The present study suggests that experimental infection with low hookworm doses is safe and is associated with improvements in glucose homoeostasis in people with Metabolic Syndrome and at risk of type 2 diabetes mellitus.

• 2023 Jul 26 How do parasitic worms prevent diabetes? An exploration of their influence on macrophage and β-cell crosstalk -- Full text | PDF

By regulating the activities of islet macrophages and β-cells (and other endocrine cells), helminth parasites shape their crosstalk. This offers a unique opportunity to exploit helminths’ mechanisms for survival in their mammalian hosts to establish an environment that preserves β-cell mass and function and thus offers the potential as a cure for both T1D and T2D.

• 2019 Dec 11 Safety and tolerability of experimental hookworm infection in humans with metabolic disease: study protocol for a phase 1b randomised controlled clinical trial — Full text | PDF

Herein we describe a randomised, double-blind, placebo-controlled Phase 1b safety and tolerability trial that will assess the effect of inoculation with 20 or 40 infective stage three larvae (L3) of Na on body fat composition, inflammation and immune response, in otherwise healthy women and men aged 18–50 with central obesity and features of MetS over 24 months.

For more research, search the following page for "diabet" using the search function on your device, i.e., Control+F on a PC, Command+F on a Mac or 'Find in page' in the drop-down menu from the three dots icon on a mobile.

• Helminthic therapy research

Personal experiences

Roughly 10-15% of type 2 diabetes cases may be an autoimmune disorder known as latent autoimmune diabetes in adults (LADA), also known as "type 1.5" diabetes. [67] A helminthic therapy user with LADA shared his experience:

I am 60+ male who developed LADA (latent auto-immune diabetes in adults - sometimes called Type 1.5) out of the blue appx 20+ years ago. It gradually evolved to becoming insulin dependent. Nov. 2014 (13 months ago), all was going pretty well until I developed flu-like symptoms… Small doses of ibuprofen kept the pain at bay, but overall health continued to deteriorate… Then came the periodic double vision and ocular aches. January 31st, I started losing vision in one eye for 10 minutes at a time… My CRP was 165 and Sed Rate was 67. Oops! Neural ophthalmologist and Rheumatology Docs put me on high dose of Prednisone (60mg) to knock out the inflammation which had localized in the fat cells behind my eyes… by June the docs could not determine what caused this inflammatory outbreak. They ruled out everything and primarily ended up with a diagnosis of auto-immune disease with inflammation of unknown origin. Put me on 20mg weekly of Methotrexate (MTX) to replace the prednisone, but there was still some residual inflammation around my eyes. Rheumatologists wanted to put me on Rituximab… Still fatigued most of the time. My primary suggested HT as another approach. I began taking HDC at end of July. After 3 doses I was feeling much better and started reducing my doses of MTX… I increased doses to 60 ova biweekly in mid-October and have stayed at that dose. I weaned off MTX and stopped it entirely in mid-Nov. My inflammation markers are back to normal (CRP is 4.4; Sed Rate is 11) and I feel better than I have in 12 months… Ophthalmologist says everything looks ok and to only call if any symptoms return… My primary and I are both pleased with how HT is going. [68]

For more reports from type 2 diabetics who have hosted helminths, see, Helminthic therapy personal stories: Diabetes type 2.

Further reading

The following papers are reviews of the scientific literature, and may be helpful for those who want to learn more about this topic:

• The Impact of Helminth Infection on the Incidence of Metabolic Syndrome: A Systematic Review and Meta-Analysis -- Full text | PDF

While infection with helminths was generally associated with improved metabolic function, there were notable differences in efficacy between parasite species.

• Helminths protect against type 1 diabetes: effects and mechanisms

Herein, we provide a comprehensive review of the effects and mechanisms underlying protection against T1D by helminths.

• Immunomodulation by helminths: Similar impact on type 1 and type 2 diabetes?

In this review, we discuss studies that have provided evidence for the beneficial impact of helminth infections on T1D and T2D.

• Parasitic helminths and their beneficial impact on type 1 and type 2 diabetes

In this review we summarize studies that investigated parasitic helminths and helminth-derived products and their impact on both type 1 and type 2 diabetes highlighting potential protective mechanisms.

• Helminth Infections, Type-2 Immune Response, and Metabolic Syndrome

This review covers the mechanisms by which helminth infection affects the occurrence of T2D and cardiovascular disease.

• The double burden of diabetes and global infection in low and middle-income countries.

This review seeks to give an overview of the current international diabetes burden, the evidence for interactions between diabetes and infection, immune mechanisms for the interaction, and potential interventions to tackle the dual burden of diabetes and infection.

• Helminth mediated modulation of Type 1 diabetes (T1D).

This review provides an overview of the findings from animal models and additionally explores the potential for translation to the clinic.

• Helminth infection and type 1 diabetes.

This review outlines basic insight into the ability of helminths to modulate the onset and progression of T1D, and frames some of the challenges that helminth-derived therapies may face in the context of clinical translation.

• Review series on helminths, immune modulation and the hygiene hypothesis: how might infection modulate the onset of type 1 diabetes?

In this review, some of the ways in which certain organisms might have influenced the onset of autoimmunity are discussed.

• Regulation of type 1 diabetes, tuberculosis, and asthma by parasites.

In this review, we summarize current findings regarding the effects of helminth infection on type 1 diabetes, tuberculosis, and asthma and discuss possible mechanisms through which helminthic parasites modulate host immunity.

• Cardiovascular disease and type 2 diabetes in evolutionary perspective: a critical role for helminths?

In this review, we survey existing studies in the non-human animal and human literature, highlight unresolved questions and suggest future directions to explore the role of helminths in the etiology of cardio-metabolic disease.

• Helminths, hygiene hypothesis and type 2 diabetes.

In this review, we summarize epidemiological evidence for the link between helminths and T2D and discuss the potential mechanisms, based on findings from experimental studies as well as the limited number of studies in humans.

• The hygiene hypothesis: an explanation for the increased frequency of insulin-dependent diabetes.

“… it is highly likely that the decline of infections is one of the major explanations for the increased frequency of insulin-dependent diabetes in developed countries.

• Do worms protect against the metabolic syndrome? A systematic review and meta-analysis.

This review aims to examine the literature on the effect of helminthic infections on metabolic outcomes in humans.

• Priming dendritic cells for th2 polarization: lessons learned from helminths and implications for metabolic disorders.

...recent literature indicates that various aspects of the Th2-associated inflammatory response contribute to metabolic homeostasis.

• Immune Regulation of Metabolic Homeostasis by Helminths and Their Molecules

In this review we discuss how helminths, which are among the strongest natural inducers of type 2 immunity, and some of their unique immunomodulatory molecules, may contribute to the maintenance of tissue-specific and whole-body metabolic homeostasis and protection against obesity-associated meta-inflammation… Importantly, controlled human infection with Necator americanus shows promising results in terms of safety and tolerability…

More recent papers are listed on the Helminthic therapy research page, which should be searched using the terms, “diabet”, “insulin”, “glucose” and “metabolic”.

Other information

Those with diabetes might also find the following information interesting.

Diabetes and the gut

• Diabetes is predominantly an intestinal disease
• Diabetes: an entirely preventable & reversible condition
• Microbiome modulator NM504 significantly improved blood glucose control and other metabolic parameters in patients with prediabetes and type 2 diabetes
• The gut microbiota modulates glycaemic control and serum metabolite profiles in non-obese diabetic mice
• Obesity, diabetes, and gut microbiota
• Heal type 2 diabetes with a probiotic?
• Causal Relationship between Diet-Induced Gut Microbiota Changes and Diabetes: A Novel Strategy to Transplant Faecalibacterium prausnitzii in Preventing Diabetes
• In-process study on fecal microbiota transplant effects on type 2 diabetes

Diabetes and nutrition

• Egg metabolites in blood related to lower risk of type 2 diabetes
• The effects of oral plain kefir supplementation on proinflammatory cytokine properties of the hyperglycemia Wistar rats induced by streptozotocin.
• Fermented milk, kefram-kefir enhances glucose uptake into insulin-responsive muscle cells.
• Kefir and diabetes
• Gluten-free diet during pregnancy alleviates signs of diabetes and celiac disease in NOD mouse offspring.
• Study adds to evidence that increasing dietary fiber reduces the risk of developing diabetes
• New study shows a plant-based vegan diet improves diabetic neuropathy pain, lowers body weight
• People with type 2 diabetes benefit from replacing refined carbohydrates with tree nuts
• 22 scientifically proven foods to control type 2 diabetes (extensive guide)
• Pistachios may lower vascular response to stress in type 2 diabetes
• 80 g per day intake of oily fish may reduce 20% risk of T2D
• Omega-3-derived PDX could be used to treat insulin resistance and type 2 diabetes
• Soy supplements appear to be safe, beneficial in diabetic men
• Consuming whey protein before meals could help improve blood glucose control
• Ground sesame seeds could help decrease heart risks in type 2 diabetics
• Certain dietary additions may help prolong insulin production
• Camel milk as an adjuvant therapy for the treatment of type 1 diabetes
• Pomegranate juice ameliorates insulin resistance and decreases fasting serum glucose in type 2 diabetes
• Intermittent fasting, cortisol and blood sugar
• Two meals a day 'effective' to treat type 2 diabetes
• Substituting vitamins and supplements for pharmaceuticals in type 2 diabetes
• Vitamin A derivative potentially treats type 2 diabetes and prevents its cardiovascular complications
• Vitamin D supplementation suppresses inflammation in patients with type 1 diabetes
• Vitamin D could lower the risk of developing diabetes
• Thiamine (vitamin B1) deficiency and diabetic polyneuropathy: compelling evidence for an interrelationship
• The role of nutritional and botanical agents in the management of type 2 diabetes Mellitus
• Diabetes-fighting potential spotted in culinary herbs
• Curcumin and diabetes: a systematic review
• Turmeric extract may prevent, even reverse diabetes (type 1 and 2)
• Chili extract may be a possible cure for both Type 1 and Type 2 diabetes
• Ginger: A diabetic's best friend
• Flavonoids associated with lower insulin resistance and better blood glucose regulation
• Coconut water study of antiglycation, hypoglycemic, and nephroprotective activities of the green dwarf variety coconut water (Cocos nucifera L.) in Alloxan-Induced Diabetic Rats
• Effect of black tea and black tea pomace polyphenols on α-glucosidase and α-amylase Inhibition, Relevant to Type 2 Diabetes Prevention
• Grape skin extract could be used to aid diabetes management
• Supplementing diet with blackberry extract causes a catabolic response with increments in insulin sensitivity in rats
• Gymnema sylvestre extract is commonly used in developing countries to treat diabetes
• Olive leaf polyphenols improve insulin sensitivity in middle-aged overweight men
• An extract of Tinospora crispa induces insulin release from pancreatic islets
• Ginkgo biloba may aid in treating type 2 diabetes

Additional approaches

• Improved oral hygiene is associated with decreased risk of new-onset diabetes: a nationwide population-based cohort study
• Study finds that being in green spaces can positively affect blood glucose in children
• Progression of diabetes stalled by traditional Chinese medicines
• Allergy drugs can help type 2 diabetes
• BCG Therapy for Type 1 Diabetes: Restoration of Balanced Immunity and Metabolism
• Combining aerobic, resistance exercise may be best for diabetes
• Sleeve gastrectomy surgery improves diabetes control better than medical care

Things to avoid

• Fluoroquinolone antibiotics linked to type 2 diabetes
• Diabetes type 3 - the electrosmog connection