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<ul><li>ecological studies</li><li>ecological fallacy</li><li>correlation is not causation</li><li>observational studies</li><li>statistical adjustment</li><li>confounding</li><li>randomized trials</li><li>factorial design</li><li>post-hoc analyses</li><li>subgroup analyses</li></ul>Methodologic morals<ul><li>“Variables with too many entanglements make observational studies a fool’s game.”</li><li>“If your intervention works only when you torture your data, it’s probably a false confession.”</li></ul>CitationsGarland CF, Garland FC.<a href="https://academic.oup.com/ije/article-abstract/9/3/227/723830"> Do sunlight and vitamin D reduce the likelihood of colon cancer?</a> Int J Epidemiol. 1980;9:227-31.Messerli FH.<a href="https://www.nejm.org/doi/abs/10.1056/NEJMon1211064"> Chocolate consumption, cognitive function, and Nobel laureates</a>. 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.<a href="https://sunindex.co/vitamind-fitness/"> Can vitamin D boost your fitness routine?</a> Dec 18, 2018.Marawan A, Kurbanova N, Qayyum R.<a href="https://academic.oup.com/eurjpc/article/26/7/750/5925119"> Association between serum vitamin D levels and cardiorespiratory fitness in the adult population of the USA</a>. Eur J Prev Cardiol. 2019;26:750-55.<a href="https://www.escardio.org/The-ESC/Press-Office/Press-releases/vitamin-d-levels-in-the-blood-linked-to-cardiorespiratory-fitness">Vitamin D levels in the blood linked to cardiorespiratory fitness.</a> European Society of Cardiology. Oct 30, 2018.Jones AM, Kirby BS, Clark IE, et al.<a href="https://journals.physiology.org/doi/full/10.1152/japplphysiol.00647.2020"> Physiological demands of running at 2-hour marathon race pace</a>. J Appl Physiol. 2021;130:369-79.Manson JE, Bassuk SS, Lee IM, et al.<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC3253961/"> 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</a>. Contemp Clin Trials. 2012;33:159-71.Manson JE, Cook NR, Lee IM, et al.<a href="https://www.nejm.org/doi/full/10.1056/NEJMoa1809944"> Vitamin D supplements and prevention of cancer and cardiovascular disease</a>. NEJM. 2019;380:33-44.Lee KL, McNeer JF, Starmer CF, et al. <a href="https://www.ahajournals.org/doi/abs/10.1161/01.cir.61.3.508">Clinical judgment and statistics: lessons from a simulated randomized trial in coronary artery disease</a>. Circulation. 1980; 61:508-15.Wood S.<a href="https://www.tctmd.com/news/vital-no-benefits-vitamin-d-and-omega-3s-reducing-major-cv-events-cancer"> VITAL: No Benefits to Vitamin D and Omega-3s in Reducing Major CV Events, Cancer</a>. TCTMD.com. Nov 10, 2018.Neale RE, Baxter C, Romero BD, et al.<a href="https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00345-4/abstract"> The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality</a>. Lancet Diabetes Endocrinol. 2022;10:120-28.Okereke OI, Reynolds CF, Mischoulon D, et al.<a href="https://jamanetwork.com/journals/jama/fullarticle/2768978"> 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</a>. JAMA. 2020;324:471-80.LeBoff MS, Murata EM, Cook NR, et al.<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC7365686/"> VITamin D and OmegA-3 TriaL (VITAL): Effects of Vitamin D Supplements on Risk of Falls in the US Population</a>. J Clin Endocrinol Metab. 2020;105:2929-38.Albert CM, Cook NR, Pester J, et al.<a href="https://jamanetwork.com/journals/jama/fullarticle/2777469"> Effect of Marine Omega-3 Fatty Acid and Vitamin D Supplementation on Incident Atrial Fibrillation: A Randomized Clinical Trial</a>. JAMA. 2021;325:1061-73.Rist PM, Buring JE, Cook NR, et al.<a href="https://www.amjmed.com/article/S0002-9343(20)31124-4/abstract"> Effect of Vitamin D and/or Marine n-3 Fatty Acid Supplementation on Changes in Migraine Frequency and Severity</a>. Am J Med. 2021;134:756-62.Christen WG, Cook NR, Manson JE, et al.<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC7596682/"> 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</a>. JAMA Ophthalmol. 2020;138:1280-89.MacFarlane LA, Cook NR, Kim E, et al.<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC7874905/"> 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</a>. Arthritis Rheumatol. 2020 Nov;72(11):1836-1844.Chou SH, Murata EM, Yu C, et al.<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC8063236/"> Effects of Vitamin D3 Supplementation on Body Composition in the VITamin D and OmegA-3 TriaL (VITAL)</a>. J Clin Endocrinol Metab. 2021;106:1377-88.Kang JH, Vyas CM, Okereke OI, et al.<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC8636504/"> Effect of vitamin D on cognitive decline: results from two ancillary studies of the VITAL randomized trial</a>. Sci Rep. 2021;11:23253.Rist PM, Buring JE, Cook NR, et al.<a href="https://onlinelibrary.wiley.com/doi/full/10.1111/ene.14623"> Effect of vitamin D and/or omega‐3 fatty acid supplementation on stroke outcomes: A randomized trial</a>. Eur J Neurol. 2021;28:809-15.Hahn J, Cook NR, Alexander EK, et al.<a href="https://www.bmj.com/content/376/bmj-2021-066452.abstract"> Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial</a>. BMJ. 2022;376:e066452LeBoff MS, Chou SH, Murata EM, et al.<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC7217747/"> Effects of Supplemental Vitamin D on Bone Health Outcomes in Women and Men in the VITamin D and OmegA-3 TriaL (VITAL)</a>. J Bone Miner Res. 2020;35:883-93.LeBoff MS, Chou SH, Ratliff KA, et al.<a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2202106"> Supplemental vitamin D and incident fractures in midlife and older adults</a>. NEJM. 2022;387:299-309.Kolata G.<a href="https://www.nytimes.com/2022/07/27/health/vitamin-d-bone-fractures.html"> Study finds another condition that vitamin D pills do not help</a>. The New York Times. July 27, 2022Jolliffe DA, Holt H, Greenig M, et al.<a href="https://www.bmj.com/content/378/bmj-2022-071230.long"> Effect of a test-and-treat approach to vitamin D supplementa...</a>

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