Hookworm Filariform

The Effect of Hookworms on Metabolic Health

Bet you never saw this one coming. We did not. But a new RCT published in Nature Communications suggests that hookworms might have benefits for the metabolic health of people with insulin resistance that puts them at risk for type 2 diabetes. This was a phase 1 study with the primary aim of confirming the safety of a novel therapy. The authors concluded:

“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. Results from this proof of concept study will inform the further development of novel preventative interventions in humans at risk of type 2 diabetes.”

A Hygiene Hypothesis of Helminths and Type 2 Diabetes

Scientists have noted for some time that in places where helminth infections are endemic, type 2 diabetes and pre-diabetes are much less common than in places where hygiene has eliminated them. Hookworms are a common type of these helminth. So this observation has given rise to a hygiene hypothesis for helminths and type 2 diabetes. In a 2017 review, Karin de Ruiter and colleagues explain:

“Helminth-induced type 2 immune responses and immune regulatory network might modulate the obesity-induced activation of inflammatory pathways that are associated with the development of insulin resistance, a strong predictor of the development of T2D.”

Thus, we see that hygiene might have a downside.

A Small Placebo Controlled Trial of Hookworms

The present study was small because the primary aim was to see if hookworm therapy might be safe enough for further research. It had three arms with a total of just 40 persons. All of them had levels of insulin resistance that put them at risk for type 2 diabetes. Investigators randomly assigned them to receive a placebo, a low dose, or a higher dose of Necator americanus hookworm larvae.

For the primary outcome, safety was adequate, with 44% of subjects experiencing mostly mild to moderate GI symptoms early in the study which resolve on their own. One subject had GI symptoms that were severe, three subjects withdrew early from the study because of adverse effects.

Fasting glucose and insulin resistance came down in the hookworm treatment groups, but not in the control group. Remember, these are secondary outcomes and thus merely suggestive of the possibility of a benefit. Real evidence of efficacy will have to come from a more robust follow-up study.

Nonetheless, the thought that hookworms might have metabolic health benefits for preventing type 2 diabetes certainly is an attention grabber.

Click here for the study in Nature Communications and here for more on the hygiene hypothesis in this context. For further perspective, click here and here.

Hookworm Filariform, image by Fernandolive / Wikimedia Commons

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August 29, 2023

3 Responses to “The Effect of Hookworms on Metabolic Health”

  1. August 29, 2023 at 8:23 am, John DiTraglia said:

    It might just be about the weight loss in the low dose hookworm group.

    • August 29, 2023 at 8:39 am, Ted said:

      If you read the paper carefully, you will find there was not a significant weight loss effect versus placebo in either group. “There were no statistically significant differences in body mass or BMI in the L3-20 or L3-40 groups compared to Placebo.”

      Two things are worth remembering:
      1. The change vs baseline weight is not a valid measure of an effect on weight.
      2. This was not a primary outcome, so not really definitive on efficacy anyway.

  2. September 01, 2023 at 1:18 pm, David Brown said:

    Question is, what sort of molecules do hookworms secrete that suppress inflammation? Here’s a clue. “This is the first report showing that hookworms secrete small molecules with both ex vivo and in vivo anti-inflammatory bioactivity, and this warrants further exploration as a novel approach to the development of anti-inflammatory drugs inspired by coevolution of gut-dwelling hookworms with their vertebrate hosts. https://journals.asm.org/doi/10.1128/iai.00851-18

    What is the connection to diabetes? “Patients with inflammatory bowel disease (IBD) are reported to have an increased risk of diabetes.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855140/