Normal Curves: Sexy Science, Serious Statistics

Vitamin D Part 2: Good for more than just your bones?

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Mar 24, 2025

Can vitamin D really boost your athletic performance while slashing cancer risks? The hosts delve into claims of this miracle vitamin, discussing studies that tease out the truth. They tackle the challenges of observational studies and ecological fallacies, revealing how misleading correlations can be. Even promising trials, like VITAL, show no major benefits after rigorous testing. Their journey underscores that while vitamin D is essential for bones, more doesn't always mean better health, urging caution in supplementation.

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INSIGHT

Vitamin D Is A Hormone Not Just A Nutrient

Vitamin D is technically a hormone that binds receptors in many cell types, suggesting potential effects beyond bones.
Lab and Petri dish findings are clues but often don't translate to real human benefits.

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INSIGHT

Limits Of Ecological Studies

Ecological studies compare groups and can suggest hypotheses from patterns like latitude and cancer.
Such studies suffer ecological fallacy and can be confounded by many non-vitamin factors.

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ANECDOTE

Chocolate And Nobel Laureates Parable

The chocolate–Nobel correlation paper was a tongue-in-cheek ecological example showing spurious country-level associations.
Some journalists nevertheless reported it seriously, illustrating misinterpretation risks.

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Episode overview and goals

00:16 • 2min

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Vitamin D biology and receptors

02:19 • 54sec

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Limits of lab findings for humans

03:12 • 1min

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Ecological studies and latitude clues

04:31 • 1min

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Ecological fallacy and satire examples

05:44 • 8min

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Observational studies: measuring vitamin D

13:45 • 3min

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Fitness study: vitamin D and VO2 max

16:30 • 3min

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Unmeasured confounding: exercise example

19:31 • 4min

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Press release misinterpretation

23:02 • 4min

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Statistical lessons from VO2 reporting

26:53 • 58sec

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Confounding, grip strength analogy

27:50 • 6min

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When statistical adjustment fails

33:40 • 4min

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Randomized trials as the solution

37:18 • 5min

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VITAL trial design and dosage

42:32 • 4min

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VITAL main results: null on major outcomes

47:01 • 46sec

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VITAL subgroup findings and caution

47:47 • 3min

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Subgroup fishing illustration

50:36 • 3min

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Press messaging and 'robustly negative'

53:58 • 2min

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D‑Health trial and opposite signals

55:43 • 3min

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VITAL ancillary (TACON) studies

58:18 • 1min

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Vitamin D and bone outcomes

59:40 • 2min

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Interpretation: minimal needs not excess

01:02:05 • 1min

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Guideline shifts and therapeutic nihilism

01:03:16 • 2min

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COVID trial in the UK and low baseline levels

01:05:40 • 2min

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Summary judgment and smooch rating

• Mentioned in 3 episodes

The vitamin D solution

M. F. Holick

The Vitamin D Solution" likely offers a comprehensive guide to understanding vitamin D, its importance for health, and how to ensure adequate levels. It may cover topics such as the role of vitamin D in bone health, immune function, and chronic disease prevention. The book likely provides practical advice on how to increase vitamin D intake through diet, supplements, and sun exposure. It may also address common misconceptions about vitamin D and provide evidence-based recommendations for optimal vitamin D levels. Readers might find guidance on topics such as choosing the right vitamin D supplement, understanding blood tests, and addressing vitamin D deficiency.

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...

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