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  

Writing in the Sciences 

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

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: 

• Demystifying Data: A Modern Approach to Statistical Understanding  
• Clinical Trials: Design, Strategy, and Analysis 
• Medical Statistics Certificate Program  
• Writing in the Sciences 
• Epidemiology and Clinical Research Graduate Certificate Program 

Program that we teach in:

Epidemiology and Clinical Research Graduate Certificate Program 

Find us on:

Kristin -  LinkedIn & Twitter/X

Regina - LinkedIn & ReginaNuzzo.com

• (00:00) - Introduction

Wear red and drive men wild with lust – or so says scientific research on color’s role in human mating. But can a simple color swap really boost a woman’s hotness score? In this episode, we delve into the evidence behind the Red Dress Effect, from a controversial first study in college men to what the latest research says about who this trick might work for (and who it might not). Along the way we encounter red monkey butts, old-Internet websites, the Winner’s Curse in scientific research, adversarial collaborations, and why size (ahem, sample size) really does matter. 

Statistical topics

• Reproducibility crisis in psychology
• Sample size
• Selection bias
• Winner’s curse
• Cohen’s d standardized effect size
• Adversarial collaboration
• Meta-analysis
• Preregistration
• Publication bias
• Statistical moderators

Methodological morals

“The smaller the sample, the flashier the result, the less you should trust it.”

“Good scientists learn from their statistical mistakes and fix them.”

References

• Clarke, G. How to Be Sexy: 7 Weird (But True) Rules of Attraction. Allure. January 23, 2013.
• Nuzzo, R. Vying for a soul mate? Psych out the competition with science. Los Angeles Times. December 8, 2008. 
• Vying for a Soul Mate on the Today Show, December 30, 2008.
• Elliot, A.J. and Niesta, D. Romantic red: red enhances men's attraction to women.  Journal of personality and social psychology. 2008; 95: 1150 – 1164. 
• Lehrer, J. The Truth Wears Off. The New Yorker, December 5, 2010. 
• MacMahon, B., Yen, S., Trichopoulos, D., Warren, K. and Nardi, G. Coffee and cancer of the pancreas. New England Journal of Medicine. 1981; 304: 630-633.
• Ioannidis, J.P. Why most published research findings are false. PLoS medicine. 2005; 2(8), e124 
• Lehmann, G.K., Elliot, A.J. and Calin-Jageman, R.J. Meta-analysis of the effect of red on perceived attractiveness. Evolutionary Psychology. 2018; 16: 1474704918802412. 
• Pazda, A.D., Thorstenson, C.A. and Elliot, A.J. The effect of red on attractiveness for highly attractive women. Curr Psychol. 2023; 42: 8066–8073

Kristin and Regina’s online courses: 

Demystifying Data: A Modern Approach to Statistical Understanding  

Clinical Trials: Design, Strategy, and Analysis 

Medical Statistics Certificate Program  

Writing in the Sciences 

Epidemiology and Clinical Research Graduate Certificate Program

Chapters

• (00:00) - Introduction

Can you really sit on your couch, pop vitamin D pills, and shave seconds off your 5k? Touted as a miracle cure-all, vitamin D is claimed to slash cancer and infection risks while boosting mood, cognition, and athletic performance. But does upping your vitamin D really make you healthier and happier? In this episode, we’ll follow the epidemiologic evidence—from clues in petri dishes through randomized trials. Along our journey, we’ll encounter chocolate-fueled Nobel Prizes, rock stars, pasty Brits, and a tangled mess of promiscuous variables.

Statistical topics

• ecological studies
• ecological fallacy
• correlation is not causation
• observational studies
• statistical adjustment
• confounding
• randomized trials
• factorial design
• post-hoc analyses
• subgroup analyses

Methodologic morals

• “Variables with too many entanglements make observational studies a fool’s game.”
• “If your intervention works only when you torture your data, it’s probably a false confession.”

Citations

Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol. 1980;9:227-31.

Messerli FH. Chocolate consumption, cognitive function, and Nobel laureates. N Engl J Med. 2012;367:1562-64.

Holick, MF. The Vitamin D Solution: A 3-Step Strategy to Cure Our Most Common Health Problems. Penguin Publishing Group, 2011. 

McMillan A. Can vitamin D boost your fitness routine? Dec 18, 2018.

Marawan A, Kurbanova N, Qayyum R. Association between serum vitamin D levels and cardiorespiratory fitness in the adult population of the USA. Eur J Prev Cardiol. 2019;26:750-55.

Vitamin D levels in the blood linked to cardiorespiratory fitness. European Society of Cardiology. Oct 30, 2018.

Jones AM, Kirby BS, Clark IE, et al. Physiological demands of running at 2-hour marathon race pace. J Appl Physiol. 2021;130:369-79.

Manson JE, Bassuk SS, Lee IM, et al. The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials. 2012;33:159-71.

Manson JE, Cook NR, Lee IM, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. NEJM. 2019;380:33-44.

Lee KL, McNeer JF, Starmer CF, et al. Clinical judgment and statistics: lessons from a simulated randomized trial in coronary artery disease. Circulation. 1980; 61:508-15.

Wood S. VITAL: No Benefits to Vitamin D and Omega-3s in Reducing Major CV Events, Cancer. TCTMD.com. Nov 10, 2018.

Neale RE, Baxter C, Romero BD, et al. The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality. Lancet Diabetes Endocrinol. 2022;10:120-28.

Okereke OI, Reynolds CF, Mischoulon D, et al. Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial. JAMA. 2020;324:471-80.

LeBoff MS, Murata EM, Cook NR, et al. VITamin D and OmegA-3 TriaL (VITAL): Effects of Vitamin D Supplements on Risk of Falls in the US Population. J Clin Endocrinol Metab. 2020;105:2929-38.

Albert CM, Cook NR, Pester J, et al. Effect of Marine Omega-3 Fatty Acid and Vitamin D Supplementation on Incident Atrial Fibrillation: A Randomized Clinical Trial. JAMA. 2021;325:1061-73.

Rist PM, Buring JE, Cook NR, et al. Effect of Vitamin D and/or Marine n-3 Fatty Acid Supplementation on Changes in Migraine Frequency and Severity. Am J Med. 2021;134:756-62.

Christen WG, Cook NR, Manson JE, et al. Effect of Vitamin D and ω-3 Fatty Acid Supplementation on Risk of Age-Related Macular Degeneration: An Ancillary Study of the VITAL Randomized Clinical Trial. JAMA Ophthalmol. 2020;138:1280-89.

MacFarlane LA, Cook NR, Kim E, et al. The Effects of Vitamin D and Marine Omega-3 Fatty Acid Supplementation on Chronic Knee Pain in Older US Adults: Results From a Randomized Trial. Arthritis Rheumatol. 2020 Nov;72(11):1836-1844.

Chou SH, Murata EM, Yu C, et al. Effects of Vitamin D3 Supplementation on Body Composition in the VITamin D and OmegA-3 TriaL (VITAL). J Clin Endocrinol Metab. 2021;106:1377-88.

Kang JH, Vyas CM, Okereke OI, et al. Effect of vitamin D on cognitive decline: results from two ancillary studies of the VITAL randomized trial. Sci Rep. 2021;11:23253.

Rist PM, Buring JE, Cook NR, et al. Effect of vitamin D and/or omega‐3 fatty acid supplementation on stroke outcomes: A randomized trial. Eur J Neurol. 2021;28:809-15.

Hahn J, Cook NR, Alexander EK, et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ. 2022;376:e066452

LeBoff MS, Chou SH, Murata EM, et al. Effects of Supplemental Vitamin D on Bone Health Outcomes in Women and Men in the VITamin D and OmegA-3 TriaL (VITAL). J Bone Miner Res. 2020;35:883-93.

LeBoff MS, Chou SH, Ratliff KA, et al. Supplemental vitamin D and incident fractures in midlife and older adults. NEJM. 2022;387:299-309.

Kolata G. Study finds another condition that vitamin D pills do not help. The New York Times. July 27, 2022

Jolliffe DA, Holt H, Greenig M, et al. Effect of a test-and-treat approach to vitamin D supplementa...

Is America really facing an epidemic of vitamin D deficiency? While this claim is widely believed, the story behind it is packed with twists, turns, and some pesky statistical cockroaches. In this episode, we’ll dive into a study on Hawaiian surfers, expose how shifting goalposts can create an epidemic, tackle dueling medical guidelines, and flex our statistical sleuthing skills. By the end, you might wonder if the real deficiency lies in the data.

Statistical topics

• dichotomization
• normal distribution 
• standard deviation
• researcher biases
• conflicts of interest
• statistical sleuthing

Methodologic morals

• “Arbitrary thresholds make for arbitrary diseases.”
• “Statistical errors are like cockroaches: Where there’s one, there’s many.”

Note that all blood vitamin D levels discussed in the podcast are 25-hydroxyvitamin D levels given in units of ng/ml. To convert from ng/ml to nmol/L, use the formula: nmol/L=2.5*ng/ml. For example, a vitamin D level of 30 ng/mL corresponds to 75 nmol/L.

Citations
Dr. Rhonda Patrick: Micronutrients for Health & Longevity. Huberman Lab Podcast. May 1, 2022

Noh CK, Lee MJ, Kim BK, et al. A Case of Nutritional Osteomalacia in Young Adult Male. J Bone Metab. 2013; 20:51-55.

Binkley N, Novotny R, Krueger D, et al. Low vitamin D status despite abundant sun exposure. J Clin Endocrinol Metab. 2007;92:2130-5. 

Malabanan A, Veronikis IE, Holick MF. Redefining Vitamin D Insufficiency. Lancet. 1998;351:805-6. 

Dawson-Hughes B, Heaney RP, Holick MF, et al. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16:713-6.

Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266-81.

Cui A, Xiao P, Ma Y, et al. Prevalence, trend, and predictor analyses of vitamin D deficiency in the US population, 2001-2018. Front Nutr. 2022;9:965376. 

Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53-8. 

Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96:1911-30. 

Manson JE, Brannon PM, Rosen CJ, et al. Vitamin D deficiency-is there really a pandemic. N Engl J Med. 2016;375:1817-20. 

Conti G, Chirico V, Lacquaniti A, et al. Vitamin D intoxication in two brothers: be careful with dietary supplements. J Pediatr Endocrinol Metab. 2014;27:763-7.

Holick, Michael, et al. The UV Advantage. Ibooks, 2004.

Holick, Michael F. The Vitamin D Solution: A 3-Step Strategy to Cure Our Most Common Health Problems. Penguin Publishing Group, 2011.

Szabo, Liz. Vitamin D, the Sunshine Supplement, Has Shadowy Money Behind It. The New York Times. August 18, 2018.

Lee JM, Smith JR, Philipp BL, Chen TC, Mathieu J, Holick MF. Vitamin D deficiency in a healthy group of mothers and newborn infants. Clin Pediatr. 2007;46:42-4. 

Holick MF. Vitamin D deficiency: what a pain it is. Mayo Clin Proc. 2003;78:1457-9.

Passeri G, Pini G, Troiano L, et al. Low Vitamin D Status, High Bone Turnover, and Bone Fractures in Centenarians. J Clin Endocrinol Metab. 2003;88:5109-15. 

Armstrong, David. The Child Abuse Contrarian. ProPublica. September 16, 2018.

Irwig MS, Kyinn M, Shefa MC. Financial Conflicts of Interest Among Authors of Endocrine Society Clinical Practice Guidelines. J Clin Endocrinol Metab. 2018;103:4333-38. 

Demay MB, Pittas AG, Bikle DD, et al. Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2024;109:1907-47.

McCartney CR, McDonnell ME, Corrigan MD, et al. Vitamin D Insufficiency and Epistemic Humility: An Endocrine Society Guideline Communication. J Clin Endocrinol Metab. 2024; 109:1948–54.

See our detailed notes here

Kristin and Regina’s online courses
Demystifying Data: A Modern Approach to Statistical Understanding 

Clinical Trials: Design, Strategy, and Analysis

Medical Statistics Certificate Program 

Writing in the Sciences

Epidemiology and Clinical Research Graduate Certificate Program

Programs that we teach in:

Epidemiology and Clinical Research Graduate Certificate Program 

Find us on:

Kristin -  LinkedIn & Twitter/X

Regina - LinkedIn & ReginaNuzzo.com

Chapters:

• (00:00) - Introduction

Sweaty t-shirt dating parties, sex pheromone dating sites, choosing your dating partner by sniffing them up — wacko fringe fads or evidence-based mating strategies? And what does your armpit stain have to do with your kids’ immune systems, or hormonal contraceptive pills, or divorce rates? 

In this episode of Normal Curves, Kristin and Regina reach back into the 1990s and revisit the scientific paper that started it all: The Sweaty T-Shirt Study. They bring a sharp eye and open mind, critically examining the study and following the line of research to today. Along the way, they encounter interesting statistical topics—including correlated observations, within-person study design, and bar-chart blasphemy—with a short, surprising detour into Neanderthal sex. 

Statistical topics

• Correlated observations
• Within-person study design
• Bar charts 
• Data and methodological transparency
• Cherry-picking
• Meta-analysis
• Multiple testing
• Post-hoc analyses

Methodological morals

“Repeat after me: Bar charts are not for numerical data.”

“Those who ignore dependencies in their data are destined for flawed conclusions.”

References

• Nuzzo, R. Ah, Love at first whiff. Los Angeles Times. May 19, 2008.
• Papamarko, S. Pheromone parties attempt to match singles by scent. Yahoo!life. April 12, 2012.
• Sainani, K. Stone Age Gene Swap. Stanford Magazine. November/December 2011.
• Aldhous, P. Darling, You Smell Wonderfully Different. New Scientist. 6 May 1995.
• Wedekind C, Seebeck T, Bettens F, Paepke AJ. MHC-dependent mate preferences in humans. Proc Biol Sci. 1995; 260(1359):245-249. doi:10.1098/rspb.1995.0087
• Hedrick P, Loeschcke V. MHC and mate selection in humans?. Trends Ecol Evol. 1996;11(1):24. doi:10.1016/0169-5347(96)80237-0
• Wedekind C, Seebeck T. Reply from C. Wedekind and T. Seebeck. Trends Ecol Evol. 1996;11(1):24-25. doi:10.1016/0169-5347(96)81061-5
• Wedekind C, Füri S. Body odour preferences in men and women: do they aim for specific MHC combinations or simply heterozygosity?. Proc Biol Sci. 1997;264(1387):1471-1479. doi:10.1098/rspb.1997.0204
• Havlíček J, Winternitz J, Roberts SC. Major histocompatibility complex-associated odour preferences and human mate choice: near and far horizons. Philos Trans R Soc Lond B Biol Sci. 2020;375(1800):20190260. doi:10.1098/rstb.2019.0260

Kristin and Regina’s online courses: 

Demystifying Data: A Modern Approach to Statistical Understanding  

Clinical Trials: Design, Strategy, and Analysis 

Medical Statistics Certificate Program  

Writing in the Sciences 

Epidemiology and Clinical Research Graduate Certificate Program

Programs that we teach in:

Epidemiology and Clinical Research Graduate Certificate Program 

Find us on:
Kristin -  LinkedIn & Twitter/X
Regina - LinkedIn & ReginaNuzzo.com

• (00:00) - Introduction

Welcome to a lively conversation about science that's like a journal club, but with less jargon, more fun, and a touch of PG-13 flair. In this introduction, Professors Regina Nuzzo and Kristin Sainani share how they met in graduate school, what they’ve been doing since then, how they’ll choose edgy topics and journal articles to dissect, and a bit about what makes them tick. Join them for their fresh, engaging take on scientific studies, data analysis, and statistical sleuthing.

Kristin and Regina’s online courses: 

Demystifying Data: A Modern Approach to Statistical Understanding  

Clinical Trials: Design, Strategy, and Analysis 

Medical Statistics Certificate Program  

Writing in the Sciences 

Program that we teach in:

Epidemiology and Clinical Research Graduate Certificate Program

Find us on:
Kristin -  LinkedIn & Twitter/X
Regina - LinkedIn & ReginaNuzzo.com

• (00:00) - Introduction to Normal Curves

Normal Curves is a podcast about sexy science & serious statistics. Ever try to make sense of a scientific study and the numbers behind it? Listen in to a lively conversation between two stats-savvy friends who break it all down with humor and clarity. Professors Regina Nuzzo of Gallaudet University and Kristin Sainani of Stanford University discuss academic papers journal club-style — except with more fun, less jargon, and some irreverent, PG-13 content sprinkled in. Join Kristin and Regina as they dissect the data, challenge the claims, and arm you with tools to assess scientific studies on your own.