Hookworms: Can parasites improve your health?
05/05/25 • 68 min
What if you could treat your prediabetes with . . . worms? Regina and Kristin dive into a surprising early-phase clinical trial on hookworm therapy—that’s right, intentionally infecting yourself with parasitic worms—to treat metabolic conditions. They dig into the biological rationale (inflammation, abdominal fat, and gut immunology), the clever study design (hello, Tabasco sauce!), and the statistical chops behind this phase 1B trial (block randomization, missing data, and nonparametric hypothesis tests). Along the way, expect self-experimenting scientists, worm sex, poop analysis, and the world’s nerdiest aphrodisiac: a well-documented protocol.
Statistical topics
- Randomized controlled trial (RCT)
- Primary and secondary outcomes
- Placebos, placebo effect, and nocebo effect
- Block randomization
- Sample size
- Double-blinding
- Missing data protocols
- Reproducible research
- Nonparametric hypothesis testing
- Kruskal-Wallis test
Methodological morals
- “Walk before you can run. Invest in simple but high-quality Phase I clinical trials.”
- “When faced with small samples, you better rank and sum, baby.”
References
- Pierce DR, McDonald M, Merone L, et al. Effect of experimental hookworm infection on insulin resistance in people at risk of type 2 diabetes. Nat Commun. 2023;14(1):4503. doi:10.1038/s41467-023-40263-4
- Nuzzo, R. What Happens When Scientists Experiment on Themselves? Reader’s Digest. Updated April 16, 2016.
- Ethics of self-experimentation
- Helminthic Therapy Wiki
- Pritchard D. Worming your way to good health [video online]. TEDx Talks. Published November 19, 2013. https://www.youtube.com/watch?v=sm5DcdZbnGA
- Chapman PR, Giacomin P, Loukas A, McCarthy JS. Experimental human hookworm infection: a narrative historical review. PLoS Negl Trop Dis. 2021;15(12):e0009908. doi:10.1371/journal.pntd.0009908
- Sobotková K, Parker W, Levá J, Růžková J, Lukeš J, Jirků Pomajbíková K. Helminth Therapy - From the Parasite Perspective. Trends Parasitol. 2019;35(7):501-515. doi:10.1016/j.pt.2019.04.009
- Zatterale F, Longo M, Naderi J, et al. Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes. Front Physiol. 2020;10:1607. Published 2020 Jan 29. doi:10.3389/fphys.2019.01607
Kristin and Regina’s online courses
Demystifying Data: A Modern Approach to Statistical Understanding
Clinical Trials: Design, Strategy, and Analysis
Medical Statistics Certificate Program
Epidemiology and Clinical Research Graduate Certificate Program
Program we teach in:
Epidemiology and Clinical Research Graduate Certificate Program
Find us on:
Kristin - LinkedIn & Twitter/X
Regina - LinkedIn & ReginaNuzzo.com
- (02:44) - What happens when scientists experiment on themselves
- (06:56) - Mail-order DIY helminthic therapy
- (09:26) - Hookworm biology
- (15:53) - Inflammation, abdominal fat, immune system, and hookworms
- (21:29) - Hookworm therapy clinical trial design
- (26:00) - Clinical trial phases deep dive
- (31:24) - Interesting placebos (sham surgeries and psychedelics)
- (37:33) - Excitement over hookworm trial open data an...
What if you could treat your prediabetes with . . . worms? Regina and Kristin dive into a surprising early-phase clinical trial on hookworm therapy—that’s right, intentionally infecting yourself with parasitic worms—to treat metabolic conditions. They dig into the biological rationale (inflammation, abdominal fat, and gut immunology), the clever study design (hello, Tabasco sauce!), and the statistical chops behind this phase 1B trial (block randomization, missing data, and nonparametric hypothesis tests). Along the way, expect self-experimenting scientists, worm sex, poop analysis, and the world’s nerdiest aphrodisiac: a well-documented protocol.
Statistical topics
- Randomized controlled trial (RCT)
- Primary and secondary outcomes
- Placebos, placebo effect, and nocebo effect
- Block randomization
- Sample size
- Double-blinding
- Missing data protocols
- Reproducible research
- Nonparametric hypothesis testing
- Kruskal-Wallis test
Methodological morals
- “Walk before you can run. Invest in simple but high-quality Phase I clinical trials.”
- “When faced with small samples, you better rank and sum, baby.”
References
- Pierce DR, McDonald M, Merone L, et al. Effect of experimental hookworm infection on insulin resistance in people at risk of type 2 diabetes. Nat Commun. 2023;14(1):4503. doi:10.1038/s41467-023-40263-4
- Nuzzo, R. What Happens When Scientists Experiment on Themselves? Reader’s Digest. Updated April 16, 2016.
- Ethics of self-experimentation
- Helminthic Therapy Wiki
- Pritchard D. Worming your way to good health [video online]. TEDx Talks. Published November 19, 2013. https://www.youtube.com/watch?v=sm5DcdZbnGA
- Chapman PR, Giacomin P, Loukas A, McCarthy JS. Experimental human hookworm infection: a narrative historical review. PLoS Negl Trop Dis. 2021;15(12):e0009908. doi:10.1371/journal.pntd.0009908
- Sobotková K, Parker W, Levá J, Růžková J, Lukeš J, Jirků Pomajbíková K. Helminth Therapy - From the Parasite Perspective. Trends Parasitol. 2019;35(7):501-515. doi:10.1016/j.pt.2019.04.009
- Zatterale F, Longo M, Naderi J, et al. Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes. Front Physiol. 2020;10:1607. Published 2020 Jan 29. doi:10.3389/fphys.2019.01607
Kristin and Regina’s online courses
Demystifying Data: A Modern Approach to Statistical Understanding
Clinical Trials: Design, Strategy, and Analysis
Medical Statistics Certificate Program
Epidemiology and Clinical Research Graduate Certificate Program
Program we teach in:
Epidemiology and Clinical Research Graduate Certificate Program
Find us on:
Kristin - LinkedIn & Twitter/X
Regina - LinkedIn & ReginaNuzzo.com
- (02:44) - What happens when scientists experiment on themselves
- (06:56) - Mail-order DIY helminthic therapy
- (09:26) - Hookworm biology
- (15:53) - Inflammation, abdominal fat, immune system, and hookworms
- (21:29) - Hookworm therapy clinical trial design
- (26:00) - Clinical trial phases deep dive
- (31:24) - Interesting placebos (sham surgeries and psychedelics)
- (37:33) - Excitement over hookworm trial open data an...
Previous Episode
Alcohol: Are happy hours good for your heart?
Does a daily glass of wine really keep the cardiologist away? It’s a claim we’ve all heard: light to moderate drinking is good for your heart. But is it science or just a convenient excuse for happy hour? In this episode, we dive into the history behind this claim, discuss the challenges of observational studies and statistical adjustment, and explore attempts at randomized trials and natural experiments to get to the bottom of this boozy debate. Grab your drink—or maybe don’t—and join us!
Statistical topics
- Statistical Adjustment
- Regression
- Residual and Unmeasured Confounding
- Randomized Trials
- Multiple Testing
- Outcome Switching
- Mendelian Randomization
Methodological morals
“Statistical adjustment cannot erase all confounding.”
“When you can’t experiment on people, let Nature experiment on people.”
Citations
- Alcohol and Drinking. Gallup Poll. 2024.
- Canada’s Guidance on Alcohol and Health. Canadian Centre on Substance Use and Addiction. 2023.
- U.S. Department of Agriculture and U.S. Department of Health and Human Services. 2020 – 2025 Dietary Guidelines for Americans. 2020.
- U.S. Department of Agriculture and U.S. Department of Health and Human Services. Alcohol and Cancer Risk: The US Surgeon General's Advisory. 2025.
- Mezue K, Osborne MT, Abohashem S, et al. Reduced stress-related neural network activity mediates the effect of alcohol on cardiovascular risk. JACC. 2023;81:2315-25.
- McPhillips D, Goodman B. Small amounts of alcohol may turn down stress in the brain, benefiting the heart, new study finds. CNN. June 12, 2023.
- Friedman GD, Klatsky AL. Is alcohol good for your health? NEJM. 1993;329:1882-3.
- Sainani K. Alcohol and Weight. Allure. July 14, 2010.
- Wang LU, Lee IM, Manson JE, et al. Alcohol consumption, weight gain, and risk of becoming overweight in middle-aged and older women. Arch Intern Med. 2010;170:453-61.
- Sainani K. Drinking and Weight. Allure. Oct 31, 2008.
- Tolstrup JS, Halkjær J, Heitmann BL, et al. Alcohol drinking frequency in relation to subsequent changes in waist circumference. Am J Clin Nutr. 2008;87:957-63.
- Rabin RC. Major Study on Drinking Will be Shut Down. New York Times. June 15, 2018.
- Mitchell G, Lesch M, McCambridge J. Alcohol industry involvement in the moderate alcohol and cardiovascular health trial. AJPH. 2020;110:485-8.
- Gepner Y, Golan R, Harman-Boehm I, et al. Effects of Initiating Moderate Alcohol Intake on Cardiometabolic Risk in Adults With Type 2 Diabetes: A 2-Year Randomized, Controlled Trial. Ann Intern Med. 2015;163:569-79.
- Slade E, Drysdale H, Goldacre B, et al. Discrepancies between prespecified and reported outcomes. Ann Intern Med. 2016;164:374.
- Biddinger KJ, Emdin CA, Haas ME, et al. Association of habitual alcohol intake with risk of cardiovascular disease. JAMA Netw Open. 2022;5:e223849.
Page with more details on the CASCADE trial
Kristin and Regina’s online courses:
Next Episode
Sugar Sag: Is Your Diet Aging You?
Wrinkles and sagging skin—just normal aging, or can you blame your sweet tooth? We dive into “sugar sag,” exploring how sugar, processed foods, and even your crispy breakfast toast might be making you look older than if you’d said no to chocolate cake and yes to broccoli. Along the way, we encounter statistical adjustment, training and test data sets, what we call “references to nowhere,” plus some cadavers and collagen. Ever heard of an AGE reader? Find out how this tool might offer a sneak peek at your date’s age—and maybe even a clue about his... um... “performance.”
Statistical topics
- Training and test sets
- Statistical adjustment
- Overfitting
- Plagiarism
- Proper citing practices
- References to nowhere
Methodologic morals
- “When you plagiarize, you steal the errors too.”
- “Overdone statistical adjustment is like overdone photo filters–at a certain point it’s just laughable.”
Citations
Collagen turnover:
- Verzijl N, DeGroot J, Thorpe SR, et al.Effect of Collagen Turnover on the Accumulation of Advanced Glycation End Products. JBC. 2000;275:39027-31.
Cadaver study:
- Hamlin CR, Kohn RR, Luschin JH. Apparent Accelerated Aging of Human Collagen in Diabetes Mellitus. Diabetes. 1975; 24: 902–904.
Studies of AGEs and diabetes and health:
- Monnier VM, Cerami A. Nonenzymatic browning in vivo: possible process for aging of long-lived proteins. Science. 1981;211:491-3.
- Brownlee M, Vlassara H, Cerami A. Nonenzymatic glycosylation and the pathogenesis of diabetic complications. Ann Intern Med. 1984;101:527-37.
- Monnier VM, Vishwanath V, Frank KE, et al. Relation between Complications of Type I Diabetes Mellitus and Collagen-Linked Fluorescence. N Engl J Med. 1986;314:403-408.
- Monnier VM, Sell DR, Abdul-Karim FW, et al. Collagen browning and cross-linking are increased in chronic experimental hyperglycemia. Relevance to diabetes and aging. Diabetes. 1988;37:867-72.
- Monnier VM, Bautista O, Kenny D, et al. Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. Diabetes 1999; 48: 870–80.
- Genuth S, Sun W, Cleary P, et al. Glycation and carboxymethyllysine levels in skin collagen predict the risk of future 10-year progression of diabetic retinopathy and nephropathy in the diabetes control and complications trial and epidemiology of diabetes interventions and complications participants with type 1 diabetes. Diabetes. 2005;54:3103-11.
- van Waateringe RP, Slagter SN, van Beek AP, et al. Skin autofluorescence, a non-invasive biomarker for advanced glycation end products, is associated with the metabolic syndrome and its individual components. Diabetol Metab Syndr. 2017;9:42.
- Kouidrat Y, Zaitouni A, Amad A, et al. Skin autofluorescence (a marker for advanced glycation end products) and erectile dysfunction in diabetes. J Diabetes Complications. 2017;3:108-113.
- Fujita N, Ishida M, Iwane T, et al. Association between Advanced Glycation End-Products, Carotenoids, and Severe Erectile Dysfunction. World J Mens Health. 2023;41:701-11.
- Uruska A, Gandecka A, Araszkiewicz A, et al. Accumulation of advanced glycation end products in the skin is accelerated in relation to insulin resistance in people with Type 1 diabetes mellitus. Diabet Med. 2019;36:620-625.
- Boersma HE, Smit AJ, Paterson AD, et al.
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