WhatSupp?

A prescription omega-3 treatment that reduces major cardiovascular events by 25%? Published in one of the world's most prestigious medical journals? Sounds pretty convincing.But what if the placebo wasn't actually doing nothing?In this episode of WhatSupp?, Dr Chaim Haber and Dr Jacob Waxman investigate the REDUCE-IT trial, a major study of prescription-strength EPA that reported an impressive reduction in cardiovascular events.The catch? Researchers have questioned whether the mineral oil used as a placebo might have negatively affected the comparison group, potentially exaggerating the apparent benefit.We explore why choosing the right placebo matters, what happened when other large omega-3 trials reached different conclusions, and why even an impressive randomized controlled trial doesn't necessarily give us the whole answer.Along the way, we discuss REDUCE-IT, JELIS and STRENGTH, relative risk reduction, and the uncomfortable reality that sometimes the evidence remains uncertain.Chapters00:00 Introduction and highlights01:00 REDUCE-IT: a 25% reduction in cardiovascular events?03:30 What makes a good placebo?05:30 Coffee, caffeine and the problem of blinding07:30 Why fish oil needs a special placebo08:15 The mineral oil controversy10:30 LDL, inflammation and the placebo group's results12:45 JELIS: supporting evidence for EPA?14:20 STRENGTH: why did another trial find no benefit?16:00 Industry funding, uncertainty and what we can concludeKey scientific referencesREDUCE-IT — Bhatt et al. (2019). Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa1812792JELIS — Yokoyama et al. (2007). Effects of Eicosapentaenoic Acid on Major Coronary Events in Hypercholesterolaemic Patients. The Lancet. https://doi.org/10.1016/S0140-6736(07)60527-3STRENGTH — Nicholls et al. (2020). Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events. JAMA. https://doi.org/10.1001/jama.2020.22258WhatSupp? - Ruining perfectly good supplement claims with evidence.Brought to you by Supp, our free tool for exploring supplement evidence: https://www.the-supp.app/suppHave a supplement claim you'd like us to investigate? Email [email protected] education and entertainment only. Nothing discussed constitutes personal medical advice.

Vitamin D seems like a no-brainer. It’s essential, deficiency is common, and millions of people take it every day. So shouldn’t we all be taking it?In the first episode of WhatSupp, Chaim and Jacob look at what happens when a very plausible idea is put to the test. We explore the evidence behind vitamin D supplementation, what large clinical trials can tell us, and why “vitamin D is important” and “everyone should take a vitamin D supplement” are not necessarily the same claim.Along the way, we get into randomized trials, observational evidence, deficiency, and one of the questions we’ll keep coming back to on WhatSupp: are we looking at something associated with good health - or something that actually causes it?Time Stamps|---|---|| 0:00 | Introduction || 4:08 | What Are Vitamins? || 5:18 | Are We Actually Deficient? || 7:35 | The Vitamin D Deficiency Pandemic || 9:35 | How Normal Levels Are Defined || 12:32 | Association Is Not Causation || 16:11 | The VITAL Randomized Trial || 19:29 | Should Healthy People Take Vitamin D? || 20:46 | How Did 30 Become the Cutoff? || 22:48 | Conflicts of Interest in Guidelines || 23:28 | IOM vs. Endocrine Society || 25:17 | The Resolution || 26:21 | Key Takeaways || 27:44 | The Insufficient Label Problem || 29:05 | Closing Remarks |You can copy and paste these directly into Spotify for Creators. The markers are also saved as chapters in the composition, so you can navigate to any section from the script.Key ReferencesVITAL — cancer & cardiovascular diseaseManson JE et al. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. NEJM, 2019.https://www.nejm.org/doi/full/10.1056/NEJMoa1809944VITAL — fracturesLeBoff MS et al. Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults. NEJM, 2022.https://www.nejm.org/doi/10.1056/NEJMoa2202106Endocrine Society 2024 Vitamin D Guidelinehttps://www.endocrine.org/clinical-practice-guidelines/vitamin-d-for-prevention-of-diseaseUSPSTF — Vitamin D Deficiency Screeninghttps://www.uspreventiveservicestaskforce.org/uspstf/recommendation/vitamin-d-deficiency-screeningRecommendations differ somewhat between populations and countries. The 2024 Endocrine Society guideline suggests that generally healthy adults under 75 are unlikely to benefit from vitamin D intake above established recommended dietary intake and suggests against routine vitamin D testing.One clarification from the episode: the USPSTF does not recommend against screening. It concludes that current evidence is insufficient to determine the balance of benefits and harms of screening asymptomatic adults.WhatSupp is brought to you by Supp, our free tool for exploring the evidence behind supplements:https://www.the-supp.app/suppGot a health claim you want us to investigate?Email [email protected]. It might become a future episode.WhatSupp is for education and entertainment only. Nothing we discuss is personal medical advice. Evidence and recommendations may change over time and may not apply to your individual circumstances. If you’re making decisions about your health or treatment, speak to an appropriately qualified healthcare professional.